Physical Function in Patients Following Surgery for Colorectal ...

Physical Function in Patients Following Surgery for

Colorectal Cancer

Kuan-Yin Lin

Bachelor of Science in Physical Therapy

Master of Science

ORCID: 0000-0002-2902-3156

Submitted in total fulfilment of the requirements of the

Degree of Doctor of Philosophy

September 2016

Department of Physiotherapy

Melbourne School of Health Sciences

The University of Melbourne

i

Abstract

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in males and

the second most common cancer in females worldwide. Surgery is the usual treatment

for CRC, however post-operative morbidity can be high. Post-operative problems can

include symptoms such as anxiety, depression, and bowel, bladder and sexual

dysfunction, poor functional exercise capacity, and low levels of physical activity.

These highly distressing problems can negatively impact patients’ health-related

quality of life (HRQoL). Although the current evidence is strong for physical activity

for patients with CRC, there is limited evidence for optimal bowel management in

patients who have undergone surgical treatment for CRC. In addition, there are no

validated instruments for measuring pelvic floor symptoms and functional exercise

capacity in both colon and rectal cancer.

This thesis aimed to (1) determine the validity and applicability of a bladder and

bowel symptom-specific questionnaire and three field walking tests for the CRC

population; (2) comprehensively understand the changes in pelvic floor symptoms and

physical and psychological outcomes in patients before and six months after surgery

for CRC; (3) investigate the feasibility of implementing a general rehabilitation

program incorporating the international physical activity guidelines for patients

following surgery for CRC; (4) explore changes in patient centred functional and

pelvic floor outcomes following the rehabilitation program; and (5) identify and

synthesize current evidence for the effectiveness of pelvic floor muscle training for

bowel dysfunction in patients who have undergone CRC surgery.

ii

Study 1 and Study 2 examined the validity and applicability of instruments/tests used

in the measurement of functional exercise capacity and bladder and bowel symptoms

of patients with CRC. The studies found that one pelvic floor symptom-specific

instrument and two functional exercise capacity field walking tests are suitable (valid

and applicable) for use with patients with CRC. The findings from Study 1 and Study

2 support the choice of outcome measures used in the subsequent studies in this thesis.

Study 3 examined the pelvic floor symptoms, physical and psychological outcomes of

patients undergoing surgery for CRC in a prospective observational study design.

Adult patients with stage I-III CRC completed pelvic floor symptom-specific

questionnaires (the Australian Pelvic Floor Questionnaire and the International

Consultation on Incontinence Questionnaire Bowel module and Urinary Incontinence

short form module) and questionnaires on physical activity levels, anxiety, depression,

and HRQoL before and six months following surgery. The main findings were that

patients experience significant bowel symptoms and persistent low physical activity

levels for up to 6 months following CRC surgery. These results suggest the need for

interventions such as rehabilitation programs or exercise interventions to increase

levels of physical activity and address bowel symptoms in patients following CRC

surgery.

Therefore, Study 4, a prospective non-randomized quasi-control study, was

undertaken to investigate the feasibility of implementing international guidelines

within an oncology rehabilitation program in patients following CRC surgery and to

explore changes in patient centred functional and pelvic floor outcomes following the

rehabilitation program. The findings showed that implementation in the oncology

rehabilitation program was feasible, and patients who have undergone the

iii

rehabilitation program had improvements in bladder and bowel symptoms, depression

and HRQoL.

Study 5, a pilot study nested within Study 4, was conducted to further explore the

changes in bladder and bowel symptoms and pelvic floor muscle clinical outcomes

measured using digital rectal examination, anorectal manometry and transperineal

ultrasound in patients following a general oncology rehabilitation program. Findings

demonstrated improved bowel symptoms from pre- to post-rehabilitation program in

patients following surgery for CRC. This suggests that general exercise may have

positive effects on pelvic floor symptoms in patients following surgery for CRC.

However, the evidence is stronger for targeted pelvic floor muscle training/exercise

than general exercise on pelvic floor symptoms in non-cancer populations, and

patients with CRC behave differently to those with non-cancer diagnoses in terms of

symptoms and treatment (i.e. surgical approaches and side effects of chemotherapy

(CT) and radiotherapy (RT)). Study 6 summarizes the current evidence on the

effectiveness of pelvic floor muscle training on bowel dysfunction in patients who

have undergone CRC surgery by systematic literature reviews. This review identified

eight studies of level III-2 to IV evidence that reported improvements in

patient-reported measures of bowel function and the HRQoL of patients who have

undergone pelvic floor muscle training following CRC surgery. This systematic

review identified gaps in the literature and revealed that there is a need for

randomized controlled trials to provide high levels of evidence of pelvic floor muscle

training for CRC populations.

iv

In conclusion, the studies outlined in this thesis identified the importance of bowel

problems following CRC surgery and suggest that an oncology rehabilitation program

may be clinically feasible for CRC. Pelvic floor muscle training is widely used in the

incontinence population, and the systematic review suggests that randomized

controlled trials are needed to confirm the effectiveness of pelvic floor muscle

training in CRC population. Given the small sample size, the evidence in this thesis

must be regarded as preliminary. Future research should investigate which subgroups

of patients with CRC (i.e. low functional exercise capacity or physical activity levels

or high levels of comorbidity at baseline) to target with exercise interventions and

which intervention (i.e. general exercise, pelvic floor muscle training, or a

combination of both) is more effective in improving pelvic floor outcomes in patients

with CRC.

v

Declaration

This is to certify that:

i. this thesis comprises only my original work towards the Doctor of Philosophy;

ii. due acknowledgment has been made in the text to all other material used; and

iii. this thesis is less than 100,000 words length, exclusive of tables, references and

appendices.

Kuan-Yin Lin

September 2016

vi

Acknowledgements

The PhD journey is a unique adventure and this journey would not have been possible

without the assistance and support of so many people I wish to thank. I would like to

express my deepest appreciation to all the members of my advisory committee,

especially my supervisors Professor Linda Denehy, Associate Professor Helena

Frawley, and Dr Catherine Granger who have constantly provided support, guidance,

encouragement and valuable suggestions at every turn of my PhD journey. I would

also like to thank my committee members, Professor Lynette Joubert, Professor Rana

Hinman and Associate Professor Jennifer Mcginley for their continuous support and

advice, thanks to you.

I would especially like to thank the participants and their families in my studies for

their generosity, courage, and support. I am extremely grateful for many of them who

expressed that they believe their participation would benefit future patients. I hope

that this work will contribute to improving survivorship care for CRC.

I would like to express my sincere gratitude and appreciation to the people who

assisted me in my research. I would like to thank the participating surgeons, especially

Professor Ian Hayes and Ms Susan Shedda, and the staff of the Department of General

Surgery at the Royal Melbourne Hospital and Melbourne Private Hospital. I would

like to thank Lisa Wilson and Annie Allman for providing patient contact details for

the study presented in Chapter 5. I would also like to thank the staff of the

Physiotherapy Department at the Royal Melbourne Hospital, especially Joel Martin,

for assisting with participant recruitment for the study presented in Chapter 4. I am

sincerely thankful to the participating surgeons and the staff from Cabrini Health and

vii

the Centre for Allied Health Research and Education at Cabrini Institute, especially

Rosemary Higgins, Michael Butler, Isabella Lees-Trinca, Hema Navaratnum,

Matthew Macauley, Ann-Marie Damatopoulos, Alice Saunder, Annika Dorey, Karen

Oliva, Jess Frydenberg, Amy Lipshutz, and Isabel LeonEscobar for their contribution

and assistance to the studies presented in Chapter 6 and Chapter 7. I would also like to

thank Dr Margaret Sherburn, Ms Angela Khera, Ms Anne-florence Plante, and Merete

Kolberg for their assistance in clinical examination training for the study presented in

Chapter 7. Thank you to Associate Professor Graham Hepworth of the Statistical

Consulting Centre at the University of Melbourne for his advice on the statistical

approach to the analyses in the studies presented in this thesis.

I would like to acknowledge and thank the grant funding from the Pat Cosh Trust,

Royal Melbourne Hospital Home Lottery Research Grant in Aid - Allied Health and

the Cabrini Foundation seed funding for supporting the studies presented in Chapter 4,

Chapter 5, Chapter 6, and Chapter 7. I would also like to acknowledge The University

of Melbourne for the Melbourne International Fee Remission Scholarship and the

Melbourne International Research Scholarships.

A special thanks to my other research colleagues and friends, in particular Katijjahbe

Binti MD Ali, Jennifer Jones, Elizabeth Proud, Elizabeth Madden, Pippa Nicolson,

Xinyang Wang, Sulakshana Balachandran, Doa El-Ansary, Raquel Sebio, Raquel

Annoni, Alexandra Eriksen, Selina Parry, Lara Edbrooke, Reiko Hara, Dolly Huang,

Chi-Yin Kao and Cristino Oliveira, thank you for your advice and friendship. Thank

you to my Taiwanese crew for their constant support and love.

viii

I would like to thank the examiners for taking time during their busy schedule to read

my thesis.

Finally, and most importantly, thank you to my family, my parents, and my sister

Kuan-Han who have always supported me all the way, through everything. Thank you

for your unconditional love and patience.

ix

Publications

Lin K-Y, Frawley H, Granger C, Denehy L. The Australian Pelvic Floor

Questionnaire is a valid measure of pelvic floor symptoms in patients following

surgery for colorectal cancer. Neurourology and Urodynamics. 2016. In press.

[Chapter 3]

Lin K-Y, Denehy L, Frawley H.C., Dimitriadis T, Martin J, Parry S, Irving L, Granger

C.L. How should functional exercise capacity be measured in colorectal cancer? a

pilot validation study. Jacobs Journal of Physiotherapy and Exercise. 2016;2(2): 017.

[Chapter 4]

Lin K-Y, Frawley H, Denehy L, Feil D, Granger C. Exercise interventions for patients

with gynecological cancer: a systematic review and meta-analysis. Physiotherapy.

2016;102(4):309-319.

Lin K-Y, Granger C, Denehy L, Frawley H. Pelvic floor muscle training for bowel

dysfunction following colorectal cancer surgery: a systematic review. Neurourology

and Urodynamics. 2015;34(8):703-12. [Chapter 8]

Publications under peer review

Lin K-Y, Denehy L, Frawley H.C., Wilson L, Granger C.L. Pelvic floor symptoms,

physical and psychological outcomes of patients following surgery for colorectal

cancer. Physiotherapy Theory and Practice. Submitted September 2016. [Chapter 5]

x

Lin K-Y, Denehy L, Granger C.L., Frawley H.C. Pelvic floor outcomes in patients

who have undergone general rehabilitation following surgery for colorectal cancer: a

pilot study. Physiotherapy Theory and Practice. Submitted December 2016. [Chapter

7]

xi

Conference Presentations

Lin K-Y, Frawley H, Granger C, Denehy L. (2016). The Australian Pelvic Floor

Questionnaire is a valid measure of pelvic floor symptoms in patients following

surgery for colorectal cancer. International Continence Society 2016. Tokyo, Japan.

Lin K-Y, Denehy L, Frawley H, Wilson L, Granger C. (2016). Pelvic floor symptoms,

physical and psychological outcomes of patients undergoing colorectal cancer surgery.

International Continence Society 2016. Tokyo, Japan.

Lin K-Y, Denehy L, Granger C, Frawley H. (2016). Pelvic floor muscle assessment in

patients who have undergone general rehabilitation following surgery for colorectal

cancer: a pilot study. International Continence Society 2016. Tokyo, Japan.

Lin K-Y, Denehy L, Frawley H, Wilson L, Granger C. (2016). Pelvic floor symptoms,

physical and psychological status of patients following surgery for colorectal cancer.

Melbourne Health Research Week Symposium 2016. Melbourne, Victoria.

Lin K-Y, Frawley H, Denehy L, Feil D, Granger C. (2015). Exercise interventions for

patients with gynaecological cancer: a systematic review and meta-analysis. APA

CONNECT Physiotherapy Conference 2015. Gold Coast, Queensland.

Lin K-Y, Granger C. Denehy L, Frawley H. (2014). Pelvic floor muscle training for

bowel dysfunction following colorectal cancer surgery: a systematic review.

Continence Foundation of Australia. Cairns, Queensland.

xii

Invited Presentations

Lin K-Y (2016). Physical Function in Patients Following Surgery for Colorectal

Cancer. St Vincent’s Hospital, Melbourne, Australia. 28th July 2016.

Lin K-Y (2015). Exercise interventions for patients with gynaecological cancer: a

systematic review and meta-analysis. CardioRespiratory Research Network,

Melbourne, Australia. 14th September 2015.

Lin K-Y (2014). Pelvic floor muscle training for bowel dysfunction following

colorectal cancer surgery. CardioRespiratory Research Network, Melbourne,

Australia. 30th July 2014.

xiii

Scholarships & Awards

Melbourne International Fee Remission Scholarship

The University of Melbourne (2013-2017)

Melbourne International Research Scholarships

The University of Melbourne (2013-2016)

Studying Abroad Scholarship

Ministry of Education, Taiwan (2013-2015)

Best Presentation Award

The University of Melbourne, School of Health Sciences (2015)

xiv

Glossary of abbreviations

6MWT 6 minute walk test

ACPS Australian clinicopathological staging

ANCOVA Analysis of covariance

ANOVA Analysis of variance

ANZCTR Australian New Zealand Clinical Trials Registry

A-P Anterior-posterior

APFQ Australian Pelvic Floor Questionnaire

APR Abdominoperineal resection

BMI Body mass index

CI Confidence interval

cmH2O Centimetre of water

COPD Chronic obstructive pulmonary disease

CPET Cardiopulmonary exercise testing

CRC Colorectal cancer

CROM Clinician reported outcome measures

CT Chemotherapy

DALY Disability-adjusted life year

DRE Digital rectal examination

EAS External anal sphincter

ECOG-PS Eastern Cooperate Oncology Group Performance Status

EMG Electromyography

EORTC QLQ-C30 European Organization for Research and Treatment of Cancer

Quality of Life Core Questionnaire

ESWT Endurance shuttle walk test

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FACT-C Functional Assessment of Cancer Therapy – Colorectal

questionnaire

FEV1 Forced expiratory volume in 1 second

FIQL Rockwood Faecal Incontinence Quality of Life Scale

FVC Forced vital capacity

HADS Hospital Anxiety and Depression Scale

HAR High anterior resection

HREC Human Research Ethics Committee

HRQoL Health-related quality of life

ICF International Classification of Functioning, Disability, and

Health

ICI International Consultation on Incontinence

ICIQ International Consultation on Incontinence Questionnaire

ICIQ-B International Consultation on Incontinence Questionnaire -

Bowel module

ICIQ-UI SF International Consultation on Incontinence Questionnaire Short

Form Questionnaire for urinary incontinence

ICS International Continence Society

IPAQ-SF International Physical Activity Questionnaire

IQR Interquartile range

ISWT Incremental shuttle walk test

JP J pouch

LAR Low anterior resection

MCID Minimal clinically important difference

MCIS Modified Cleveland Incontinence Score

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MET Metabolic equivalent

MVC Maximum voluntary contraction

NA Not available

NCCN National Comprehensive Cancer Network

NES Nutrition Self-Efficacy Scale

NOS Newcastle-Ottawa Scale

NR Not reported

OR Odds ratio

PA Physical activity

PES Physical Exercise Self-Efficacy Scale

PFM Pelvic floor muscle

PhD Doctor of Philosophy

PRISMA Preferred Reporting Items for Systematic Reviews and

Meta-Analyses

PROM Patient reported outcome measures

PRS Perineal rectosigmoidectomy

QLQ-CR29 European Organization for Research and Treatment of Cancer

Quality of Life colorectal cancer modules

RCT Randomized controlled trial

RR Relative risk

RT Radiotherapy

SD Standard deviation

SF-36 Short Form 36 questionnaire

SpO2 Oxygen saturation

STROBE Strengthening the Reporting of Observational Studies in

xvii

Epidemiology

TAFE Technical and further education

TEM Transanal endoscopic microsurgery

TME Total mesorectal excision

TNM Tumour-node-metastasis

TPUS Transperineal ultrasound

TREND Transparent Reporting of Evaluations with Nonrandomized

Designs

UDI Urogenital Distress Inventory

ULAR Ultra-low anterior resection

VO2max Peak oxygen consumption

WHO World Health Organization

WIS Wexner Incontinence Scale

xviii

Table of contents

Chapter 1. Introduction .................................................................................................. 1

1.1 Background of the problem ............................................................................. 1

1.2 Evidence Gaps in the literature ........................................................................ 4

1.3 Significance of the research ............................................................................. 5

1.4 Research aims .................................................................................................. 6

1.5 Overview of the thesis ..................................................................................... 8

Chapter 2. Colorectal cancer ........................................................................................ 12

2.1 Introduction .................................................................................................... 12

2.2 Definition ....................................................................................................... 12

2.3 Epidemiology ................................................................................................. 13

2.3.1 Incidence ............................................................................................. 13

2.3.2 Mortality and survival ......................................................................... 16

2.3.3 Prevalence ........................................................................................... 18

2.4 Cost and burden of CRC ................................................................................ 19

2.5 Etiology / risk factors ..................................................................................... 20

2.5.1 Sociodemographic factors (age and gender) ....................................... 21

2.5.2 Medical factors (Inflammatory bowel disease, history of CRC,

hereditary factors, and diabetes) .................................................................. 22

2.5.3 Lifestyle factors (obesity, physical inactivity, smoking, alcohol

consumption, and diet) ................................................................................. 23

2.6 Histopathology ............................................................................................... 27

2.7 Cancer staging ................................................................................................ 28

2.8 Signs and symptoms of CRC at diagnosis ..................................................... 31

2.9 Treatment ....................................................................................................... 32

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2.9.1 Overview of CRC treatment ............................................................... 32

2.9.1.1 Surgical approaches for CRC ................................................... 32

2.9.2 Adjuvant medical treatment (radiotherapy and chemotherapy) .......... 37

2.10 Side effects and symptoms following treatment .......................................... 41

2.10.1 Pelvic floor dysfunction .................................................................... 41

2.10.2 Physical function (functional exercise capacity and muscle strength)

...................................................................................................................... 45

2.10.3 Level of physical activity .................................................................. 46

2.10.4 Anxiety and depression ..................................................................... 48

2.10.5 Health-related quality of life (HRQoL) ............................................ 49

2.11 Summary ...................................................................................................... 50

Chapter 3. Outcome Measures ..................................................................................... 51

3.1 Introduction .................................................................................................... 51

3.2 Patient reported outcome-measures (PROM) ................................................ 52

3.2.1 Pelvic floor symptoms ........................................................................ 52

3.2.2 Pelvic floor signs ................................................................................. 54

3.2.3 Levels of physical activity .................................................................. 55

3.2.4 Anxiety and depression ....................................................................... 56

3.2.5 Health related quality of life (HRQoL) ............................................... 56

3.2.6 Self efficacy ........................................................................................ 57

3.3 Clinical-reported outcome measures / performance-based outcome measures

............................................................................................................................. 58

3.3.1 Pelvic floor muscle function ............................................................... 58

3.3.2 Functional exercise capacity ............................................................... 60

3.3.3 Muscle strength ................................................................................... 62

3.4 Summary of outcome measures chosen for the studies in this thesis ............ 63

xx

3.5 Validation study of the Australian Pelvic Floor Questionnaire in patients

following surgery for colorectal cancer ............................................................... 63

3.5.1 Introduction ......................................................................................... 64

3.5.1.1 Study aims ................................................................................ 64

3.5.2 Materials and Methods ........................................................................ 65

3.5.3 Results ................................................................................................. 68

3.5.4 Discussion ........................................................................................... 80

3.5.5 Summary ............................................................................................. 83

Chapter 4. How should functional exercise capacity be measured in colorectal cancer?

a pilot validation study ................................................................................................. 84

4.1 Introduction .................................................................................................... 84

4.1.1 Study aims and hypotheses ................................................................. 85

4.2 Materials and Methods ................................................................................... 85

4.2.1 Study design, setting and participants ................................................. 86

4.2.2 Procedure ............................................................................................ 86

4.2.3 Measures ............................................................................................. 86

4.2.4 Statistical analyses .............................................................................. 89

4.3 Results ............................................................................................................ 90

4.4 Discussion .................................................................................................... 100

4.5 Summary ...................................................................................................... 103

Chapter 5. Pelvic floor symptoms, physical and psychological outcomes of patients

following surgery for colorectal cancer ..................................................................... 105

5.1 Introduction .................................................................................................. 105

5.1.1 Study aims and hypotheses ............................................................... 106

5.2 Materials and Methods ................................................................................. 106

5.2.1 Study design and participants ........................................................... 106

xxi

5.2.2 Outcome measures ............................................................................ 107

5.2.3 Statistical analysis ............................................................................. 109

5.3 Results .......................................................................................................... 110

5.3.1 Subgroup analysis over three assessment time points (before surgery,

6-week after surgery, and 6-month after surgery) ...................................... 117

5.4 Discussion .................................................................................................... 123

5.5 Summary ...................................................................................................... 126

Chapter 6. A general oncology rehabilitation program for patients following surgery

for colorectal cancer – a pilot study ........................................................................... 128

6.1 Introduction .................................................................................................. 128

6.1.1 Study aims and hypotheses ............................................................... 129

6.2 Methods ....................................................................................................... 130

6.2.1 Participants ........................................................................................ 130

6.2.2 Intervention ....................................................................................... 132

6.2.3 Outcomes .......................................................................................... 132

6.2.4 Sample size ....................................................................................... 137

6.2.5 Statistical Methods ............................................................................ 137

6.3 Results .......................................................................................................... 137

6.3.1 Participant flow ................................................................................. 137

6.3.2 Recruitment ....................................................................................... 140

6.3.3 Baseline Data and Baseline Equivalence .......................................... 140

6.3.4 Primary outcomes ............................................................................. 143

6.3.5 Secondary outcomes ......................................................................... 145

6.4 Discussion .................................................................................................... 154

6.5 Summary ...................................................................................................... 161

xxii

Chapter 7. Pelvic floor outcomes in patients who have undergone general oncology

rehabilitation following surgery for colorectal cancer: a pilot study ......................... 162

7.1 Introduction .................................................................................................. 162

7.1.1 Study aims ......................................................................................... 163

7.2 Materials and Methods ................................................................................. 163

7.2.1 Participants ........................................................................................ 163

7.2.2 Interventions ..................................................................................... 164

7.2.3 Outcomes .......................................................................................... 164

7.2.4 Statistical Methods ............................................................................ 167

7.3 Results .......................................................................................................... 168

7.3.1 Participant flow and recruitment ....................................................... 168

7.3.2 Baseline Data and Baseline Equivalence .......................................... 170

7.3.3 Outcomes .......................................................................................... 172

7.4 Discussion .................................................................................................... 191

7.5 Summary ...................................................................................................... 195

Chapter 8. Pelvic floor muscle training for bowel dysfunction following colorectal

cancer surgery: a systematic review .......................................................................... 196

8.1 Introduction .................................................................................................. 196

8.2 Review aim .................................................................................................. 197

8.3 Methods ....................................................................................................... 197

8.3.1 Literature search ................................................................................ 197

8.3.2 Selection criteria ............................................................................... 197

8.3.3 Screening of papers ........................................................................... 199

8.3.4 Risk of bias ....................................................................................... 199

8.3.5 Data extraction .................................................................................. 200

8.4 Results .......................................................................................................... 200

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8.4.1 Search strategy and study selection .................................................. 200

8.4.2 Study and participant characteristics ................................................ 203

8.4.3 Effects of pelvic floor muscle training in patients following colorectal

cancer surgery ............................................................................................ 214

8.5 Discussion .................................................................................................... 219

8.5.1 Study limitations ............................................................................... 222

8.6 Summary ...................................................................................................... 222

8.7 Additional papers published since the systematic review was undertaken .. 223

8.7.1 Summary of additional study ............................................................ 223

Chapter 9. Conclusion and future directions .............................................................. 225

9.1 Overview of main findings .......................................................................... 225

9.2 Strengths and limitations of the present research ........................................ 226

9.3 Future directions .......................................................................................... 226

References .................................................................................................................. 230

Appendices ................................................................................................................. 282

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List of Appendices

Appendix 4.1 Ethics Approval Documentation (Study 2) ......................................... 282

Appendix 4.2 Data collection sheets (Study 2) .......................................................... 283


Appendix 5.2 Data collection sheets (Study 3) .......................................................... 319


Appendix 6.2 “Exercise for home” sheet (Study 4) ................................................... 350

Appendix 6.3 Exercise diary (Study 4) ...................................................................... 354

Appendix 6.4 Data Collection Sheets (Study 4) ........................................................ 358


Appendix 7.2 Data Collection Sheets (Study 5) ........................................................ 395

Appendix 8.1 Systematic review article .................................................................... 404

Appendix 8.2 Example of search strategy ................................................................. 414

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List of Tables

Table 2-1: Risk factors for colorectal cancer ............................................................... 21

Table 2-2: WHO histological classification of tumours of the colon and rectum ........ 28

Table 2-3: Australian clinicopathological staging ........................................................ 29

Table 2-4: TNM CRC staging ...................................................................................... 29

Table 2-5: TNM, Duke and ACPS cancer staging for CRC ......................................... 30

Table 2-6: Most common symptoms or side effects from cancer treatment ................ 40

Table 3-1: Demographic and clinical variables in participants with and without

bladder symptoms following surgery for colorectal cancer ......................................... 69

Table 3-2: Demographic and clinical variables in participants with and without bowel

symptoms following surgery for colorectal cancer ...................................................... 71

Table 3-3: Characteristics of participants..................................................................... 74

Table 3-4: Severity of bladder and bowel symptoms ................................................... 75

Table 3-5: Correlations between AFPQ bladder and bowel domains, ICIQ-UI SF and

ICIQ-B in total cohort (n=44) ...................................................................................... 76

Table 3-6: Correlations between AFPQ bladder and bowel domains, ICIQ-UI SF, and

ICIQ-B in males (n = 25) ............................................................................................. 77

Table 3-7: Correlations between AFPQ bladder and bowel domains, ICIQ-B, and

ICIQ-UI SF in females (n = 19) ................................................................................... 77

Table 3-8: Agreement between AFPQ bladder and bowel domains, ICIQ-B, and

ICIQ-UI SF for symptomatic participants ................................................................... 78

Table 3-9: Association between demographic and clinical variables and bladder and

bowel symptoms in participants following surgery for colorectal cancer ................... 79

Table 4-1: Medical and social demographics (n = 10) ................................................. 92

Table 4-2: Test results .................................................................................................. 93

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Table 4-3: Pearson’s correlations between CPET VO2peak and 6MWT distance,

ISWT distance, and ESWT time (N = 10) ................................................................... 97

Table 4-4: Pearson’s correlations between 6MWT distance, ISWT distance, ESWT

time, CPET VO2peak and respiratory function .............................................................. 97


time, and CPET VO2peak and ECOG-PS, HRQoL physical function and global health

domain scores, and hand-grip strength ........................................................................ 97

Table 4-6: Discriminant validity: Difference between participants with or without

self-rated walking limitations in all walking tests ....................................................... 98

Table 4-7: Changes in BORG scores with each test .................................................. 100

Table 5-1: Demographic and medical data at baseline (n = 30)................................. 112

Table 5-2: Pelvic floor symptoms, physical activity levels, and psychological

outcomes .................................................................................................................... 114

Table 5-3: Number of participants categorized according to level of severity of

bladder and bowel symptoms and physical activity, n (%) ........................................ 116

Table 5-4: Health-related quality of life outcomes .................................................... 119

Table 6-1: Demographic and medical data at baseline .............................................. 141

Table 6-2: Adherence: Exercise diary, mean (SD) or n (%) ....................................... 145

Table 6-3: Outcomes: baseline to post-intervention .................................................. 147

Table 6-4: Health-related quality of life outcomes .................................................... 150

Table 6-5: Global rate of change immediately post-intervention or 8 weeks following

baseline ...................................................................................................................... 154

Table 7-1: Participant demographics and clinical characteristics .............................. 171

Table 7-2: Results of pelvic floor muscle clinical assessment in rehabilitation group

.................................................................................................................................... 173

Table 7-3: Pelvic floor symptom scores ..................................................................... 181

xxvii

Table 7-4: Bladder diary results in rehabilitation group ............................................ 183

Table 7-5: Bowel diary results in rehabilitation group .............................................. 184

Table 7-6: Pelvic floor muscle strength of rehabilitation group Spearman’s correlation

at baseline (n = 9) ....................................................................................................... 186

Table 7-7: Pelvic floor muscle strength Spearman’s correlation immediately post-

rehabilitation program (n = 9) .................................................................................... 187

Table 7-8: Pelvic floor muscle strength Spearman’s correlation at 6 months follow-up

(n = 8) ......................................................................................................................... 188

Table 7-9: Linear regression analyses examining the relationship between different

clinical measures of PFM function and severity of pelvic floor symptoms .............. 189

Table 8-1: Risk of bias in reviewed observational trials using the Newcastle-Ottawa

Scale ........................................................................................................................... 204

Table 8-2: Participants in reviewed studies................................................................ 206

Table 8-3: Intervention programs in reviewed studies ............................................... 210

Table 8-4: Results: patient-reported bowel function pre- and post-intervention ....... 215

xxviii

List of Figures

Figure 2.1: Incidence of top ten leading cancers in Victoria, Australia during the

period from 2009 to 2014 (Cancer Council Victoria, 2016) ........................................ 15

Figure 2.2: Incidence rate of colorectal cancer in Victoria, Australia from 2005 to

2014 (Cancer Council Victoria, 2016) ......................................................................... 16

Figure 2.3: Mortality from colorectal cancer in Victoria, Australia during the period

from 2005 to 2014 (Cancer Council Victoria, 2016) ................................................... 18

Figure 2.4: Average age-specific incidence rate of CRC in Victoria, Australia during

the period from 2009 to 2014 (Cancer Council Victoria, 2016) .................................. 22

Figure 2.5: Surgical procedures for colon cancer: (A) right hemicolectomy; (B)

transverse colectomy; (C) left hemicolectomy; (D) total colectomy (Cancer Council

Victoria, 2013). ............................................................................................................ 34

Figure 2.6: Surgical procedures for rectal cancer: (A) high anterior resection; (B)

ultra-low anterior resection; (C) abdominoperineal resection (Cancer Council Victoria,

2013). ........................................................................................................................... 35

Figure 3.1: Flow chart of the two studies .................................................................... 73

Figure 4.1: STROBE flow chart of the study .............................................................. 91

Figure 4.2: Relationship between 6MWT distance (A), ISWT distance (B), and ESWT

time (C) with CPET VO2peak. ....................................................................................... 96

Figure 5.1: Flow of patients throughout the study ..................................................... 111

Figure 5.2: Bar graph showing mean scores of role functioning for pre-and

post-operative assessments ........................................................................................ 118

Figure 6.1: Patient flow through the study ................................................................. 139

Figure 7.1: Pelvic floor measures in the sagittal plane .............................................. 167

Figure 7.2: Flow chart of the study ............................................................................ 169

xxix

Figure 7.3: Change in raw scores of anorectal manometry variables over time for

participants with CRC ................................................................................................ 175

Figure 7.4: Change in raw scores of ultrasound variables over time for participants

with CRC. .................................................................................................................. 178

Figure 7.5: Change in raw scores of bladder and bowel symptoms over time for

participants with CRC. ............................................................................................... 180

Figure 8.1: PRISMA flow diagram of study selection process. ................................. 202

Chapter 1. Introduction

1


1.1 Background of the problem

Worldwide, colorectal cancer (CRC) is the third most commonly diagnosed cancer

and the fourth leading cause of cancer mortality (Arnold et al., 2016; Torre et al.,

2015). The five-year survival for CRC is about 60% internationally (Favoriti et al.,

2016). In Australia, CRC is the second most commonly diagnosed cancer in both

males and females. The incidence rate of CRC in 2011 was 8,351 cases per 100,000

men and 6,800 cases per 100,000 women (Australian Institute of Health and Welfare,

2015a, 2015b). Despite the high incidence of CRC, the five-year survival for CRC is

improving in Australia; the rate was 66.4% for males and 67.4% for females in the

period 2007-2011 (Australian Institute of Health and Welfare, 2014). This indicates

that most patients with CRC today can expect to live many years after their diagnosis.

Due to the improving survival rates and aging of the population, the number of CRC

survivors in the community is expected to continue to increase (Favoriti et al., 2016;

Parry, Kent, Mariotto, Alfano, & Rowland, 2011).

The medical treatment for CRC includes surgery, chemotherapy (CT), and/or

radiotherapy (RT). The type of treatment combination depends on the patient’s stage

of the cancer disease, tumour location and characteristics, and their performance

status (Stintzing, 2014). In Australia in 2000, approximately 82% of patients had

undergone surgery for CRC and adjuvant CT was offered to 49% of patients with

rectal cancer and 39% of patients with colon cancer (McGrath, Leong, Armstrong, &

Spigelman, 2004). Although medical treatment is associated with survival benefits

(Aran, Victorino, Thuler, & Ferreira, 2016), patients often experience significant

morbidity following treatment. Problems include high levels of symptoms (anxiety,

depression, and bowel, bladder and sexual dysfunction), poor functional exercise

capacity, and low levels of physical activity (PA) (Bailey et al., 2015; Brant et al.,

2011; Hamaker et al., 2015; Jensen, Houborg, Norager, Henriksen, & Laurberg;

Lange & van de Velde, 2011; Lynch, Cerin, Owen, & Aitken, 2007; Siefert; Tomoda


2

& Furusawa, 1985; van Duijvendijk et al., 2003). These symptoms can significantly

impact on the patient’s daily functioning and health-related quality of life (HRQoL).

These symptoms can also be mapped into the main domains of the World Health

Organization (WHO)’s International Classification of Functioning, Disability, and

Health (ICF) framework: health condition, body structures and functions, activities,

participation, and environmental and personal factors (Bours et al., 2016; World

Health Organization, 2001). Due to the growing number of CRC survivors,

management of the disease burden and post-operative symptoms is a priority.

The Australian Physical Activity and Sedentary Behaviour Guidelines recommend

that older adults, 65 years and above, undertake at least 30 minutes of

moderate-intensity PA on most days of the week (Brown, Moorhead, & Marshall,

2008). Similar recommendations (exercise at least 150 minutes per week with

addition of strength training exercise at least 2 days per week) were made for cancer

survivors in the American College of Sports Medicine (Schmitz et al., 2010) and

American Cancer Society Guidelines (Rock et al., 2012), as well as with advice to

avoid sedentary time and return to normal daily activities as quickly as possible after

surgery. The guidelines suggest that exercise is safe and effective in improving

physical functioning, HRQoL, and cancer-related fatigue in cancer survivors both

during and after cancer treatment (Rock et al., 2012; Schmitz et al., 2010). Exercise

interventions in the adult cancer populations are associated with benefits on

cardiorespiratory fitness, HRQoL, mood, symptoms and treatment side-effects (Conn,

Hafdahl, Porock, McDaniel, & Nielsen, 2006; Knols, Aaronson, Uebelhart, Fransen,

& Aufdemkampe, 2005; Schmitz et al., 2005). A recent systematic review and

meta-analysis of five randomized controlled trials (RCT) with a total of 238 patients

with CRC found strong evidence for short-term improvements of physical fitness in

patients after exercise interventions compared with controls (Cramer, Lauche, Klose,

Dobos, & Langhorst, 2013). However, the effects of exercise on HRQoL and the

long-term effects of exercise interventions were inconclusive due to the small number

of trials (Cramer et al., 2013). Moreover, the feasibility of implementing an exercise

program in an Australian healthcare setting has not been reported.


3

In addition to impaired physical function and low levels of PA, pelvic floor

dysfunction (bladder, bowel, and sexual dysfunction) is prevalent in patients

following treatment for CRC (Fish & Temple, 2014). While it is widely recognized

that bladder, bowel, and sexual dysfunction is more common and severe in patients

following rectal cancer surgery than patients with colon cancer (Fish & Temple, 2014;

Martin, Haren, Marshall, Lange, & Wittert, 2011; Panjari et al., 2012; Scheer et al.,

2011; van Duijvendijk et al., 2003), small studies have shown that patients with colon

cancer also suffer from pelvic floor dysfunction following surgery (Phipps, Braitman,

Stites, & Leighton, 2008; Tomoda & Furusawa, 1985). Urinary dysfunction (38% -

60%) and sexual dysfunction (male: 44% - 63%; female: 25%) among patients

following surgery for CRC are common (Panjari et al., 2012; Perera et al., 2008). The

most frequently reported bowel problems after sphincter-saving surgery for CRC are

incomplete evacuation (75%), excessive flatus (75%), faecal urgency (73%), straining

at stool (61%), peri-anal soreness or itching (49%), bloating (44%), and faecal

incontinence (38%) (Nikoletti et al., 2008). A study by Phipps et al. also found that

bowel problems (63%) are common among colon cancer survivors (Phipps et al.,

2008). Altered bowel function and urogenital dysfunction may profoundly influence

CRC patients’ personal relationships, social activities (Vironen, Kairaluoma, Aalto, &

Kellokumpu, 2006), work, and HRQoL (Wilson, Alexander, & Kind, 2006), and

impose significant economic burden to the healthcare system and the community.

Although changes in pelvic floor symptoms before and after CRC surgery

(predominantly in rectal cancer) have been documented in the literature, currently

there are no studies that provide information regarding bladder, bowel and sexual

symptoms, and physical and psychological outcomes in one patient cohort which

includes both colon and rectal cancer populations. To date, there is a large body of

evidence regarding the effectiveness of PA or general exercise on physical and

psychological outcomes in patients with CRC, however the role of general exercise in

the management of pelvic floor dysfunction in CRC is not well understood.

To evaluate the effectiveness of an intervention or the appropriateness of care

provided to a specific patient cohort, it is necessary to measure changes in the

outcomes of an intervention using measurement instruments which are validated and


4

applicable to the population. Although many performance-based instruments and

patient-reported outcome measures have been used to measure symptoms, function

and HRQoL in mixed cancer populations or patients with rectal cancer in clinical

practice and research studies (Aaronson et al., 1993; Emmertsen & Laurberg, 2012;

Schmidt, Vogt, Thiel, Jäger, & Banzer, 2013; Whistance et al., 2009), to date, there

are no validated instruments for measuring pelvic floor symptoms and functional

exercise capacity in both colon and rectal cancer. As the ratio of colon to rectal cancer

in Australia is approximately 2:1 (Australian Institute of Health and Welfare, 2015a,

2015b), it is potentially useful to have measurements instruments which are valid and

applicable across both tumour streams.

In addition to the lack of appropriate instruments for measuring pelvic floor

symptoms and functional exercise capacity in CRC, based on the current literature,

there is limited evidence on the optimal management of pelvic floor dysfunction in

CRC. Although it is clear that exercise improves several important health outcomes of

patients following CRC treatment, no studies have investigated the effects of a

general exercise on pelvic floor dysfunction in CRC populations, and hence there is

limited understanding of the changes in pelvic floor dysfunction in patients following

a general oncology rehabilitation. The following section lists the evidence gaps

identified in the literature.

1.2 Evidence Gaps in the literature

The key gaps identified in the research and literature are as follows:

1. There is lack of evidence on the validity of the measurement instruments for

pelvic floor outcomes (bladder, bowel, and sexual dysfunction) and functional

exercise capacity for use in patients with CRC.

2. Information regarding pelvic floor symptoms and physical and psychological

outcomes in patients following surgery for both rectal and colon cancer is scarce.


5

3. The feasibility of implementing an exercise program incorporating the American

Cancer Society physical activity guidelines for patients with CRC in an Australian

healthcare setting has not been reported.

4. There are no studies investigating the potential impact of a general oncology

rehabilitation program on pelvic floor outcomes (bladder, bowel, and sexual

function) in patients with CRC.

5. Although evidence of the benefits of general exercise interventions for patients

with CRC is rapidly emerging, there are no exercise or physiotherapy guidelines

for treating pelvic floor symptoms after CRC surgery.

1.3 Significance of the research

Colorectal cancer is the second most commonly diagnosed cancer in Australia; one in

12 patients are diagnosed with CRC by the age of 85 (Australian Institute of Health

and Welfare, 2014). In Australia, cancer ranks sixth in terms of estimated total health

system expenditure on chronic diseases, with CRC accounting for the highest

expenditure (7.7%) (Australian Institute of Health and Welfare, 2013). Whilst

survivorship care has become a major area of interest due to the growing number of

CRC survivors, the prevalence of post-discharge unmet needs is high. Approximately

21% of patients’ unmet needs persist at least 6 months after their hospital discharge

(Harrison et al., 2011). Post-operative problems may include physical, psychological,

and pelvic floor symptoms (bladder, bowel and sexual dysfunction), which can

severely impact on the patient’s HRQoL. Therefore, it is important to understand the

natural history of pelvic floor symptoms and other physical and psychological

outcomes in this patient cohort in order to develop appropriate rehabilitation programs

or exercise interventions to address these de novo or residual symptoms for patients

with CRC.

Increased levels of PA after CRC diagnosis are associated with lower risk of mortality

(Van Blarigan & Meyerhardt, 2015). However, CRC survivors following cancer

diagnosis are more likely to be insufficiently active than community populations


6

(Hawkes, Lynch, Youlden, Owen, & Aitken, 2008). While cardiac or pulmonary

rehabilitation programs are offered as standard care to patients with coronary heart

disease (Anderson et al., 2016) and chronic obstructive pulmonary disease (COPD)

(Nici & ZuWallack, 2015), no rehabilitation program has been recommended and

implemented as routine care for patients after CRC treatment in Australia or in most

parts of the world. Such a program may be able to appropriately address the physical,

psychological, and social challenges and needs of patients after CRC treatment.

Hence, an oncology rehabilitation program which implements international

survivorship care and exercise guidelines and addresses the diverse range of concerns

related to CRC may change the clinical care pathway for this population.

Specific pelvic floor muscle (PFM) training has been used routinely for treatment of

incontinence in clinical practice (Bø & Herbert, 2013), however there is a paucity of

evidence on changes in pelvic floor outcomes (bladder, bowel, and sexual dysfunction)

in patients with CRC following a general oncology rehabilitation program, which

does not include specific PFM training. Information on the prospective changes in

pelvic floor outcomes following a general oncology rehabilitation program in patients

following CRC surgery will add evidence to the current literature regarding the role of

general exercise on pelvic floor outcomes.

The findings of this thesis will (1) provide suggestions on the choice of appropriate

instruments to measure functional exercise capacity and pelvic floor outcomes in

CRC and (2) add valuable evidence on the role of general exercise in CRC

rehabilitation with view to (3) evaluate the impact of an oncology rehabilitation

program on physical, psychological and pelvic floor outcomes; if found to be

beneficial, the program may be further translated into practice and be provided as part

of standard care in clinical pathway for patients with CRC.

1.4 Research aims

This thesis focuses on physical function of patients following surgery for CRC. The

first section of the thesis relates to measurement of pelvic floor symptoms and


7

physical and psychological outcomes of patients with CRC. The aims of these studies

were to:

1. Evaluate the construct validity and clinical utility of the Australian Pelvic Floor

Questionnaire (APFQ) against two alternative measures of the severity of bladder and

bowel symptoms in males and females following surgery for CRC;

2. Determine demographic and clinical variables as clinical predictors of bladder and

bowel symptoms following CRC surgery;

3. Explore the criterion validity of three field walking tests (6 minute walk test

[6MWT], incremental shuttle walk test [ISWT] and endurance shuttle walk test

[ESWT]) against the gold standard laboratory test (cardiopulmonary exercise testing

[CPET]) to measure functional exercise capacity in CRC;

4. Investigate the relationships of 6MWT, ISWT, ESWT, and CPET to

patient-reported physical function, hand grip strength and HRQoL, and to determine

the clinical applicability/practicality of these tests;

5. Prospectively measure pelvic floor symptoms in patients before and up to six

months after surgery for CRC;

6. Assess PA levels, psychological outcomes, and HRQoL in patients before and up to

six months after surgery for CRC.

The second section of the thesis relates to the impact of a general oncology

rehabilitation program on physical, psychological, and pelvic floor outcomes, and the

effectiveness of PFM training on pelvic floor outcomes in patients following surgery

for CRC through a systematic review of the evidence. The aims of these studies were

to:

1. Investigate the feasibility of implementing a general oncology rehabilitation

program incorporating the physical activity guidelines for patients following surgery

for CRC;


8

2. Explore changes in functional exercise capacity, muscle strength, psychological

outcomes, level of PA, self-efficacy, pelvic floor symptoms, and HRQoL in patients

before and after a general oncology rehabilitation program;

3. Explore changes in pelvic floor clinical outcomes in patients who have undergone a

general oncology rehabilitation program following surgery for CRC;

4. Assess the associations between different clinical measures of PFM function and

severity of pelvic floor symptoms at baseline, immediately post-oncology

rehabilitation, and at 6-months follow-up;

5. Identify, evaluate and synthesize the evidence examining the effectiveness of PFM

training on bowel dysfunction in patients who have undergone CRC surgery.

1.5 Overview of the thesis

There are six studies which form the main body of this thesis.

Chapter 2 provides an overview to the background of the studies and summarizes the

epidemiology, aetiology / risk factors, cancer staging, signs and symptoms of the

disease, the medical treatment of the disease, as well as the clinical impact of

treatment on the patient. The post-treatment symptoms including pelvic floor

dysfunction (bowel, bladder, and sexual dysfunction), impaired functional exercise

capacity, low levels of PA, anxiety, depression, and poor HRQoL are discussed.

Chapter 3 consists of two parts. The first part introduces the psychometric properties

of the measurement instruments specifically used in the studies. Part two reports on

Study 1 in which an exploratory analysis of data from two prospective studies (Study

3 and Study 4) was undertaken. The study sample consisted of 44 participants.

Bladder and bowel symptoms were measured using three validated questionnaires: the

APFQ, the International Consultation on Incontinence Questionnaire (ICIQ) Short

Form Questionnaire for urinary incontinence (ICIQ-UI SF), and the International


9

Consultation on Incontinence Questionnaire-Bowel Module (ICIQ-B) post-cancer

treatment. The relationships between these questionnaires are described and the

predictors of postoperative bladder or bowel symptoms following CRC surgery are

reported. Results of Study 1 support the choice of outcome measures used to assess

pelvic floor symptoms in Studies 3, 4, and 5.

Chapter 4 reports on Study 2 in which the criterion validity of three common field

walking tests was explored against CPET, the gold standard laboratory measure of

functional exercise capacity, in patients with CRC. The observational study included

ten participants with stage I-III CRC who were evaluated within six months of their

last treatment (surgery, CT, RT or targeted treatment). Functional exercise capacity

was assessed by the 6MWT, ISWT, ESWT, and CPET. Additional measures included

hand-grip strength, physical function, respiratory function and HRQoL. The results on

the participant stability between tests, criterion validity, construct validity,

discriminant validity, and clinical applicability are provided. The results of Study 2

support the use of 6MWT in Study 4.

Chapter 5 reports on Study 3 where pelvic floor symptoms, PA levels, psychological

outcomes, and HRQoL of patients undergoing CRC surgery were measured across the

natural history of disease. The prospective observational study included 30

participants with stage I-III CRC. The primary outcome was pelvic floor symptoms

measured with the APFQ. Supplementary data were also collected from the ICIQ-B

and ICIQ-UI SF. Secondary outcomes were PA levels, anxiety, depression, and

HRQoL evaluated with questionnaires. Outcomes were measured pre-operatively and

six-months post-operatively. Changes in outcomes of interest over 6 months of the

assessment period are described. Results from Study 3 provide justification for the

need for rehabilitation programs or exercise interventions to increase levels of PA and

address bowel symptoms in patients following CRC surgery.

Chapter 6 reports on Study 4 where the feasibility of implementing a general

oncology rehabilitation program incorporating the international physical activity

guidelines in an Australian healthcare setting for patients following CRC surgery was

undertaken. The changes in patient centred functional and pelvic floor outcomes

following the rehabilitation program were evaluated. The pilot non-randomized


10

quasi-control study included 12 participants in the ‘rehabilitation’ group and 10 in the

‘questionnaire’ (quasi-control) group. The rehabilitation group participated in an

8-week exercise and education program. The questionnaire group was asked to

complete the postal questionnaires only and did not undertake the rehabilitation

program. The outcome measures were obtained at baseline and immediately

post-intervention or at 8-weeks following the baseline assessment. The feasibility of

implementation of the general oncology rehabilitation program and the changes in the

outcomes of interest are described. Findings from Study 4 inform clinicians of the

feasibility and benefits of the general oncology rehabilitation, which should be

considered as a useful component in the standard care for patients with CRC.

Chapter 7 reports on Study 5 which explored the PFM outcomes measured using

digital rectal examination (DRE), anorectal manometry, transperineal ultrasound and

standardized questionnaires in an opportunistic sample of volunteers from the

‘rehabilitation’ group in Study 4. The changes in and differences between bladder and

bowel outcomes in patients following general oncology rehabilitation compared with

a questionnaire group are described. The results of Study 5 provide useful information

for future studies to design an appropriately powered large RCT to study the

long-term effect of a general oncology rehabilitation on pelvic floor outcomes in

patients with CRC. The correlations between different clinical PFM outcome

measures and the associations between clinical outcome measures and self-reported

pelvic floor symptoms are presented. Conclusion and recommendations for future

studies to establish the optimal outcome measure for pelvic floor outcomes in this

patient population are made.

Chapter 8 reports on Study 6 in which a systematic review was undertaken to identify,

evaluate and synthesize the evidence examining the effectiveness of PFM training on

bowel dysfunction in patients who have undergone CRC surgery. Eligible studies

were systematically reviewed, data were extracted, and risk of bias was assessed.

Results of studies were summarized. Results of Study 6 support the need for RCTs to

confirm the effects of PFM training for patients after CRC surgery.


11

Chapter 9 concludes the thesis by summarizing the findings from all studies,

discussing the major strengths and weaknesses of the studies and recommending the

directions of future research.

Chapters 3, 4, 5, 7, and 8 within this thesis contain content that is substantially

unchanged from the content of multi-author papers which have been either published

or are currently under review.

Chapter 2. Colorectal cancer

12


2.1 Introduction

This chapter provides an overview of CRC. The first half of the chapter focuses on the

epidemiology, aetiology and medical treatment including cancer staging. The second

half of the chapter focuses on the disease burden associated with CRC including

symptoms, treatment side effects. This chapter provides background information

relevant to the studies reported in this thesis.

2.2 Definition

The following definitions apply to this thesis:

Colon cancer: “cancer that forms in the tissues of the colon (the longest part of the

large intestine). Most colon cancers are adenocarcinomas (cancers that begin in cells

that make and release mucus and other fluids).” (Australian Institute of Health and

Welfare & Australian Government Department of Health, 2016)

Rectal cancer: “cancer that forms in the tissues of the rectum (the last several inches

of the large intestine closest to the anus).” (Australian Institute of Health and Welfare

& Australian Government Department of Health, 2016)

Right hemicolectomy: “surgical procedure performed for tumours of the cecum and

ascending colon; removal of the right side of the colon” (Cancer Council Victoria,

2013; McKenzie, Barnes, & Schwartz, 2005)

Transverse colectomy: “surgical procedure for tumours of the transverse colon;

removal of the middle part of the colon” (Cancer Council Victoria, 2013; McKenzie

et al., 2005)


13

Left hemicolectomy: “surgical procedure for descending or sigmoid colonic lesions;

removal of the left side of the colon” (Cancer Council Victoria, 2013; McKenzie et al.,

2005)

Total colectomy: “surgical procedure for the entire colon; removal of all of the colon”

(Cancer Council Victoria, 2013; McKenzie et al., 2005)

Low anterior resection: “removal of the sigmoid colon and upper rectum”(American

Cancer Society, 2014)

Abdominoperineal resection: “removal of the sigmoid colon and entire rectum and

anus” (Cancer Council Victoria, 2013)

Proctectomy with total mesorectal excision: “removal of the rectum together with the

mesorectum around it and the surrounding mesorectal fascia.” (American Cancer

Society, 2014)

Coloanal anastomosis: “the colon is connected to the anus.”(American Cancer Society,

2014)

Colostomy: “opening formed by diverting the end of colon to the abdominal

wall”(Cancer Council Victoria, 2013)

Ileostomy: “opening constructed by bringing the end of the ileum to the surface of the

skin”(Cancer Council Victoria, 2013)

2.3 Epidemiology

2.3.1 Incidence

Colorectal cancer is the third most commonly diagnosed cancer worldwide, with an

estimation of 1.4 million new cases diagnosed in 2012 (Arnold et al., 2016). In males,


14

CRC is the third most common cancer diagnosed after lung cancer and prostate cancer,

accounting for 10% of all new cancer diagnoses yearly (Ferlay et al., 2013). In

females, it is the second most common cancer diagnosed after breast cancer,

accounting for 9% of new cancer diagnoses worldwide (Ferlay et al., 2013). While the

incidence of CRC is increasing in several European, Latin American and Asian

countries, and Canada over the most recent 10-year period (2002-2012), the incidence

rate declined in the United States, Australia, New Zealand, Iceland, Czech Republic

and Japan (Arnold et al., 2016). The most marked decline occurred in the United

States, where CRC incidence rates have declined about 3.2% per year over the last 10

years (National Cancer Institute, 2016).

In Australia, CRC is the second most commonly diagnosed cancer after prostate

cancer in males, and after breast cancer in females (Australian Institute of Health and

Welfare, 2014). In 2011, 10,037 (66%) new cases of colon cancer and 5,114 (34%)

new cases of rectal cancer were diagnosed (Australian Institute of Health and Welfare,

2015a, 2015b). More than half (55%) of these cases were diagnosed in males

(Australian Institute of Health and Welfare, 2015a, 2015b). In 2016, the estimated

number of new cases of CRC is 17,520 (9,810 males and 7,710 females (Australian

Institute of Health and Welfare, 2014). In Australia, the age-standardised incidence

rates of CRC remained stable for males (75 cases per 100,000 males) but decreased

from 53 cases to 50 cases per 100,000 females from 2003 to 2012 (Australian Institute

of Health and Welfare, 2016b). The mean age of patients at time of first diagnosis of

CRC is 69 in males and 71 in females (Australian Institute of Health and Welfare,

2014).

In Victoria (the state of Australia where the studies which form this thesis were

undertaken), CRC is the third most commonly diagnosed cancer after prostate and

breast cancer (Farrugia et al., 2015) (Figure 2.1) with 3,712 new cases diagnosed in

2014 (2,004 males and 1,708 females). The age-standardised incidence rates were 68

and 53 per 100,000 Victorian males and females, respectively (Cancer Council

Victoria, 2016).


15

Figure 2.1: Incidence of top ten leading cancers in Victoria, Australia during the

period from 2009 to 2014 (Cancer Council Victoria, 2016)

Over the ten year period from 2005 to 2014, CRC incidence rates in Victoria declined

by 14.1% for males and 5.4% for females (Figure 2.2). The improvement in

diagnostic technology and the introduction of screening programs (i.e. the Australian

National Bowel Cancer Screening Program) may have contributed to the decline in

the incidence rate (Australian Institute of Health and Welfare & Australian

Government Department of Health, 2016). Despite the declining incidence rates

shown by the global, Australian, and Victorian data, CRC remains one of the leading

types of cancers internationally, nationally and regionally. Greater attention and

efforts are needed to put into this population in order to alleviate the burden of CRC

worldwide.


16

Figure 2.2: Incidence rate of colorectal cancer in Victoria, Australia from 2005 to

2014 (Cancer Council Victoria, 2016)

2.3.2 Mortality and survival

Worldwide, CRC is the fourth leading cause of cancer-related deaths, responsible for

approximately 8% of all cancer deaths (Favoriti et al., 2016). In 2012, about 694,000

patients died from CRC worldwide; the age-standardized mortality rate was 8.3 per

100,000 persons. The mortality rate for males (10 per 100,000) was higher than that

for females (6.9 per 100,000) (Ferlay et al., 2013). Although the mortality rate

increased in several less developed and low- to middle-income countries, it stabilized

or decreased in many highly developed countries, such as Singapore, Finland, Norway,

Slovakia, United Kingdom, Netherlands, Italy, Malta, Slovenia, United States, Israel,

Austria, Czech Republic, Iceland, France, Japan, Australia, and New Zealand from

2002 to 2012 (Arnold et al., 2016).

In Australia, CRC is the third leading cause of all cancer deaths among males and

females (Australian Institute of Health and Welfare, 2014). In 2012, 1,962 patients

(1,021 males and 941 females) died of colon cancer in Australia (Australian Institute


17

of Health and Welfare, 2015a). There were 2,018 deaths from rectal cancer in 2012

(1,187 males and 831 females) (Australian Institute of Health and Welfare, 2015b).

Although it was estimated that the number of patients who died from CRC would

increase to 4,120 deaths in 2016 (2,170 males and 1,950 females) (Australian Institute

of Health and Welfare, 2014), the age-standardized mortality rate of CRC decreased

from 24 deaths to 19 deaths per 100,000 males and 16 deaths to 13 deaths per 100,000

females between 2004 and 2013 (Australian Institute of Health and Welfare, 2016b).

The decreasing mortality rate may be due to the improvements in CRC treatment

and/or early detection of the disease (Center, Jemal, Smith, & Ward, 2009; Favoriti et

al., 2016). The decreasing mortality rates also reflect the increase in survival rate. In

Australia, the one-year and five-year relative survival rates for CRC were 85% and

67% in 2007 to 2011 (Australian Institute of Health and Welfare, 2014), which are

comparable to the worldwide data of one- and 5-year relative survival rates, 83% and

65%, respectively (Favoriti et al., 2016). This indicates that most patients with CRC

today can expect to live many years after their diagnosis. The one-year, five-year, and

ten-year relative survivals increased from 76%, 54%, and 49% in the period

1988-1993 to 85%, 66%, and 61% in the period 2006-2010 (Australian Institute of

Health and Welfare, 2012). However, the 5-year survival rate of CRC is highly

dependent upon stage of disease at time of diagnosis and ranges from 90% for

localized cancers detected at very early stage to 13% for patients diagnosed with

metastatic disease (National Cancer Institute, 2016).

In Victoria, CRC is the second most common cause of cancer death after lung cancer,

with age-standardised mortality rates of 24 per 100,000 males and 16 per 100,000

women in 2014 (Cancer Council Victoria, 2016). Over the ten year period from 2005

to 2014, mortality rates declined by 6.4% for males and 6.9% for females (Cancer

Council Victoria, 2016) (Figure 2.3). In 2013, the 5-year relative survival for CRC

was 67%; a significant increase from 50% in 1988-1992 to 67% in 2008-2012

(Farrugia et al., 2015). The number of CRC survivors living in the community in

Victoria is increasing. Therefore research which aims to address survivorship needs of

this growing population is warranted.


18

Figure 2.3: Mortality from colorectal cancer in Victoria, Australia during the period

from 2005 to 2014 (Cancer Council Victoria, 2016)

2.3.3 Prevalence

Worldwide in 2012, the 1-year, 3-year, and 5-year prevalence (number of persons

who were diagnosed with CRC and were still alive at the end of 2012) for CRC was

0.9, 2.4, and 3.5 million persons respectively (Ferlay et al., 2013). In Australia, the

one year prevalence for CRC was 6,835 for males and 5,495 for females at the end of

2009 (Australian Institute of Health and Welfare, 2014). At the end of 2009, 26,700

males and 21,896 females who had been diagnosed with CRC in the previous 5 years

were still alive (Australian Institute of Health and Welfare, 2014). Colorectal cancer

accounted for 13% of total male and female five-year prevalence of all cancers

(Australian Institute of Health and Welfare, 2014). The prevalence for CRC increases

with increasing age, with 4.1% of Australians aged 80 and over having a history of

CRC (Australian Institute of Health and Welfare, 2012). Not only is CRC responsible

for significant patient burden, the increasing number of CRC survivors is also likely

to contribute to rising economic burden on the health care system and society

(Ananda et al., 2016). This is due to increased focus on implementation of primary


19

(diet and PA) and secondary (screening program) prevention; increased requirements

for medical treatment and surveillance (which can last for many years after a

diagnosis), and the requirement for the development of new and improved curative

treatments (Tarraga Lopez, Albero, & Rodriguez-Montes, 2014; Van Cutsem et al.,

2013).

2.4 Cost and burden of CRC

Burden of disease can be analysed by quantifying the impact of a disease or injury on

an individual or population, using the disability-adjusted life year (DALY) measure

(Australian Institute of Health and Welfare, 2014). The DALY uses time as a

common currency; one DALY is one year of ‘healthy life’ lost due to premature death,

prolonged illness or disability (AIHW & AACR, 2012; Australian Institute of Health

and Welfare, 2016a). The more DALYs associated with a particular disease, the

greater the burden (AIHW & AACR, 2012).

Worldwide, it was estimated that 169 million years of healthy life were lost due to

cancer in 2008 (Soerjomataram et al., 2012). In Australia, cancer was the leading

cause of the burden of disease in 2011 (19% of the total DALYs) (Australian Institute

of Health and Welfare, 2016a). In 2011, CRC was estimated to account for 2.1% of

total DALYs in Australia. In males, CRC (53,084 DALYs) ranked twelfth (2.2% of

the total DALYs) in terms of top causes of total burden in 2011; in females, CRC

(39,338 DALYs) ranked sixteenth (1.9% of total DALYs) (Australian Institute of

Health and Welfare, 2016a). Moreover, CRC accounted for almost 11% of the total

cancer burden (dying early from cancer) and ranked second after lung cancer as the

top causes of total cancer burden in 2011 (Australian Institute of Health and Welfare,

2016a).

According to the Australian Institute of Health and Welfare report, the total

expenditure on CRC was $427.35 million, accounting for 9.4% of all cancer

expenditure and attributing to the highest expenditure for individuals aged 65 and

above in 2008-2009 (Australian Institute of Health and Welfare, 2013). The estimated


20

health system expenditures on CRC were $248 million (10%) for males and $180

million, (8.7%) for females (Australian Institute of Health and Welfare, 2013). In

2012 - 2013, there were 914,993 cancer-related hospitalizations, which indicated that

cancer was responsible for 1 in 10 hospitalizations in Australia (Australian Institute of

Health Welfare, 2015). The number of total hospitalizations with a principal diagnosis

of cancer was 415,130 and CRC was the fourth most common cancer type recorded as

principal diagnosis, accounting for 7% (28,213) of all hospitalizations in 2012 - 2013

(Australian Institute of Health Welfare, 2015). The costs of treating CRC in Australia

was estimated to be $34,337 per patient for stage I CRC, $43,776 for stage II colon

cancer, $79,375 for stage III colon cancer, $86,317 for stage II and III rectal cancer,

and $71,156 for stage IV CRC (Ananda et al., 2016). The cost of treatment is likely to

increase with the availability of more effective systemic treatments, improved

imaging modalities and other emerging treatment strategies (Ananda et al., 2016). As

the costs reported in the study by Ananda et al. were calculated using public hospital

data, the figures may be an underestimate of the true cost in private systems.

2.5 Etiology / risk factors

There are multiple factors associated with the development of CRC. These include

age, gender, inflammatory bowel disease, history of CRC in first-degree relatives,

diabetes, obesity, physical inactivity, smoking, high alcohol consumption, and diet

high in fat or animal products (Brenner, Kloor, & Pox, 2014; Johnson et al., 2013)

(Table 2-1).


21

Table 2-1: Risk factors for colorectal cancer

Sociodemographic factors Age

Gender

Medical factors Inflammatory bowel disease

History of CRC

Family history/hereditary factors

Diabetes Mellitus

Lifestyle factors Obesity

Physical inactivity

Smoking

Alcohol consumption

Diet

2.5.1 Sociodemographic factors (age and gender)

Advancing age is an independent risk factor associated with the development of CRC

(Day & Velayos, 2014). In Australia, the mean age at CRC diagnosis was 70 years in

2011 (69 years for males and 71 years for females) (Australian Institute of Health and

Welfare, 2014). In 2011, the risk for CRC was 1 in 23 before the age of 75 years and

1 in 12 before the age of 85 years (Australian Institute of Health and Welfare, 2014).

In males, the risk of being diagnosed with CRC before the age of 75 years and the age

of 85 years was 1 in 19 and 1 in 10, respectively. In comparison, the risk of a female

being diagnosed with CRC was 1 in 28 before the age of 75 years and 1 in 15 before

the age of 85 years (Australian Institute of Health and Welfare, 2014). In Victoria, the

median age at CRC diagnosis was 70 years for males and 72 years for females in 2013

(Cancer Council Victoria, 2016). The risk of being diagnosed with CRC by the age of

75 was 1 in 22 for males and 1 in 30 for females (Farrugia et al., 2015). Figure 2.4

shows the average age-specific incidence rate of CRC in Victoria, Australia.


22

Figure 2.4: Average age-specific incidence rate of CRC in Victoria, Australia during

the period from 2009 to 2014 (Cancer Council Victoria, 2016)

A meta-analysis by Nguyen et al. which included studies conducted in North America,

Europe, and Asia, has provided strong evidence showing that males are at greater risk

of developing advanced colorectal neoplasia across all age groups (pooled relative

risk [RR] estimate 1.8) (Nguyen, Bent, Chen, & Terdiman, 2009). In Australia, males

have a slightly higher risk of developing CRC than females (male 55% vs. female

45%) (Australian Institute of Health and Welfare, 2014). While the proportion of

males and females with colon cancer in 2011 was fairly equal, the ratio of males and

females with rectal cancer was nearly 3:2 (Australian Institute of Health and Welfare,

2015a, 2015b).

2.5.2 Medical factors (Inflammatory bowel disease, history of CRC, hereditary

factors, and diabetes)

It has been widely accepted that patients with inflammatory bowel disease (i.e.

ulcerative colitis or Crohn’s disease) (Kim & Chang, 2014); family history (Noe,

Schroy, Demierre, Babayan, & Geller, 2008); inherited syndromes, including Lynch

syndrome (or hereditary nonpolyposis CRC), familial adenomatous polyposis, and


23

mutY Homolog-associated polyposis, juvenile polyposis, hereditary mixed polyposis,

and Peutz-Jeghers syndrome (Ballinger & Anggiansah, 2007; Jasperson, Tuohy,

Neklason, & Burt, 2010); or diabetes mellitus (Yuhara et al., 2011) have an increased

risk of developing CRC. As most of the medical factors are non-modifiable, the

details of which are not covered in this thesis. Nevertheless, identification of patients

with these medical factors who are at risk for CRC and surveillance for these patients

are critical in reducing the risk of developing CRC.

2.5.3 Lifestyle factors (obesity, physical inactivity, smoking, alcohol consumption,

and diet)

One in three cancers in Australia is attributable to a modifiable risk factor (Whiteman

et al., 2015). Colorectal cancer is the second leading potentially preventable cancer

after lung cancer, indicating that most cases of CRC in Australia could be prevented if

the population avoided exposure to known risk factors such as tobacco smoke, alcohol,

obesity, insufficient PA, and diet, which independently raise an individual’s risk of

the disease (Whiteman et al., 2015).

Obesity

Obesity is a major health issue in Australia, with 63% of adults being classified as

overweight or obese (body mass index [BMI] ≥ 25 kg/m2), among which 28% are

classified as obese (BMI ≥ 30 kg/m2) (Leung & Funder, 2014). In Victoria, the rates

of overweight and obesity are about 36% and 17% respectively (Rahman & Harding,

2013). A national longitudinal study has projected that the prevalence of obesity will

increase to 70% by 2025, with approximately less than one third of the Australian

population classified as normal weight (BMI 18.5-24.9 kg/m2) (Walls et al., 2012).

Substantial number of cancers are attributable to overweight or obesity in Australia,

amongst which the evidence is strong and convincing for a link with CRC (Kendall et

al., 2015). A meta-analysis has indicated that individuals with obesity have a 40%

greater risk of CRC compared with individuals with normal weight (RR = 1.4 (95%

confidence interval [CI]: 1.3 - 1.5) in males; RR = 1.1 (95% CI: 1.0 - 1.2) in females)


24

(Huxley et al., 2009). The RR was nonsignificantly higher for colon cancer than rectal

cancer: RR 1.2 (95% CI: 1.1 - 1.4) versus 1.1 (95% CI: 1.0 - 1.3) (Huxley et al., 2009).

A study with a large cohort of Australian adults has shown that high BMI is

associated with the development of CRC with a hazard ratio of 1.1 (95% CI 1.1 - 1.2)

in males and 1.1 (95% 1.0 - 1.1) in females (Harding et al., 2015).

Research which focuses on the mechanisms underlying the link between obesity and

CRC is emerging, and several pathways have been postulated, although the evidence

is inconsistent. These include mechanisms involving insulin and IGF signalling

pathways, adipokines secretion, chronic inflammation, metabolic syndrome and gut

microbiota (Laiyemo, 2014). Obesity-induced insulin resistance causes high levels of

plasma insulin, glucose and fatty acids; exposure of the colonocyte to increased

concentration of insulin, glucose, and fatty acid, which may induce a mitogenic effect

within these cells; metabolic perturbations; and alterations in cell signalling pathways

and oxidative stress (Gunter & Leitzmann, 2006). Chronic inflammation leads to the

secretion of inflammatory cytokines (i.e. tumour necrosis factor-a, monocyte

chemoattractant protein-1, and interleukin-6), which are associated with CRC (Guffey,

Fan, Singh, & Murphy, 2013). As prediagnosis BMI may be associated with higher

all-cause mortality, and CRC-specific mortality or recurrence (Campbell et al., 2012;

Vrieling & Kampman, 2010), maintaining a healthy body weight is important

throughout life.

Physical inactivity

Physical activity is beneficial for physical and psychological health and well-being of

the general population (Teixeira, Carraca, Markland, Silva, & Ryan, 2012). In

Australia between 2002 and 2004, the prevalence of "low PA" (< 600 metabolic

equivalent [MET]-minutes/week) of the adult population was 17%. Females were

more sedentary than males, with a prevalence of low PA 20% versus 14% in males

(Bauman et al., 2009). Low PA is associated with increased risk of CRC. A

meta-analysis found a significant negative correlation between PA and the risk of

developing CRC (RR = 0.9 per increase of 2 in the standardized PA score [95% CI:


25

0.8 - 0.9]) (Johnson et al., 2013). The negative association with PA is stronger for

colon cancer than for rectal cancer (RR reduction 24% (95% CI: 18% - 29%) versus

6% (95% CI: -3% - 14%) (Huxley et al., 2009). In Australia, approximately 5% of

CRC cases (4.2% in males and 5.4% in females) diagnosed in 2010 were attributable

to insufficient PA (< 300 minutes [5 hours ~ 30 MET-hours] of moderate activity per

week) (Whiteman et al., 2015). Possible mechanisms for the protective effect of PA

against CRC include changes in gastrointestinal transit time, modulation of chronic

inflammation, enhanced immune function, altered gene mutation, changes in insulin

levels, prostaglandin levels, insulin-like growth factors, bile acid secretion, serum

cholesterol and gastrointestinal and pancreatic hormone profiles, and weight loss

(Harriss et al., 2007; Quadrilatero & Hoffman-Goetz, 2003). However, due to the lack

of empirical data to support any of the proposed mechanisms, it is likely that the link

between PA and CRC is the results of a combination of these mechanisms

(Quadrilatero & Hoffman-Goetz, 2003). Research has shown that PA is not only

associated with the risk of CRC but may also influence survival after a diagnosis of

CRC and physical recovery after CRC surgery (Boyle, Fritschi, Platell, & Heyworth,

2013; Hardikar et al., 2015; Onerup et al., 2016). Therefore, PA is an important factor

in preventing CRC and promoting long-term health and survival after cancer

treatment.

Smoking

Smoking increases the risk of CRC (Boyle et al., 2013). In Australia, approximately

6.4% (6% in males and 7% in females) of CRC cases diagnosed in 2010 was

independently attributable to smoking (Whiteman et al., 2015). A meta-analysis has

shown that the pooled risk estimates for current smoker versus never smoker, former

smoker versus never smokers, and ever smokers versus never smokers were 1.1

(95% CI 1.0 - 1.2), 1.2 (95% CI 1.1 - 1.2), and 1.2 (95% CI 1.1 - 1.3) respectively

(Botteri et al., 2008). Moreover, significant dose-response relationship (i.e. increase in

risk with increasing smoking consumption) was observed in the meta-analysis, and

the risk increased by 7.8% (95% CI 5.7% - 10.0%) for every additional 10 cigarettes

(Botteri et al., 2008). The associated risk is higher for rectal cancers than for colon


26

cancer (Liang, Chen, & Giovannucci, 2009). The carcinogens in tobacco are

understood to form and to increase the growth rate of adenomatous polyps, the

precursor lesions of CRC (Botteri et al., 2008; Haggar & Boushey, 2009).

Alcohol consumption

Alcohol consumption is associated with an increase in risk for CRC (Fedirko et al.,

2011). In Australia, 9% of CRC cases (13% in males and 4% in females) diagnosed in

2010 were independently attributable to alcohol consumption (Whiteman et al., 2015).

A meta-analysis has shown that the pooled RRs of CRC for any alcohol drinking

versus no or occasional drinking was 1.1 (95% CI 1.1 - 1.2); the RRs were for light (≤

12.5 g/day), moderate (12.6 to 49.9 g/day) and heavy drinking (≥ 50 g/day) were 1.1

(95% CI 1.0 - 1.1), 1.2 (95% CI 1.2 - 1.3) and 1.4 (95% CI 1.3 - 1.5), respectively

(Wang, Duan, Yang, & Lin, 2015). Meta-analyses have indicated that the risk of CRC

increased dose-dependently and the association of alcohol drinking with the risk of

CRC did not differ by sex and tumour site (i.e. colon or rectum) (Fedirko et al., 2011;

Wang et al., 2015), however the World Cancer Research Fund /American Institute of

Cancer Research reported that alcohol consumption seems to have a stronger negative

effect in males compared to females (Roswall & Weiderpass, 2015). Potential

mechanisms connecting CRC with alcohol consumption have been studied in human,

animal, and cell line studies and these are related to acetaldehyde production in the

colon (i.e. the effect of acetaldehyde on the disruption of epithelial tight junctions and

cell adhesion, mucosal damage after ethanol consumption, increased degradation of

folate, stimulation of rectal carcinogenesis, increased effect of carcinogens by

acetaldehyde, and stimulation of acetaldehyde on cell proliferation in intestinal crypt

cells) (Oyesanmi et al., 2010).

Diet

Diet strongly influences the risk of CRC (Haggar & Boushey, 2009). In Australia,

35% of CRC cases (40% in males and 29% in females) in 2010 were independently

attributable to insufficient fibre and red and processed meat (Whiteman et al., 2015).


27

A meta-analysis has demonstrated that the pooled RR of CRC for the highest versus

lowest intake of red and processed meats was 1.2 (95% CI 1.1 - 1.3) and the RR for

every 100 g/day increase was 1.1 (95% CI = 1.0 - 1.2) (Chan et al., 2011). Similar

associations were observed for colon and rectal cancer (Chan et al., 2011). Potential

underlying mechanisms for the association between red meat consumption and CRC

include the presence of haeme iron in red meat, production of heterocyclic aromatic

amines and polycyclic aromatic hydrocarbons resulting from meat cooked at high

temperatures, and formation of N-nitroso compounds (Baena & Salinas, 2015; Haggar

& Boushey, 2009).

Fibre has been shown to have a protective effect on CRC (Baena & Salinas, 2015).

The RR of developing CRC was 0.9 (95% CI 0.9 - 0.9) for 10 g daily of total dietary

fibre, 0.9 (95% CI 0.8 - 1.1) for fruit fibre, 1.0 (95% CI 0.9 - 1.1) for vegetable fibre,

0.6 (95% CI 0.3 - 1.4) for legume fibre, and 0.9 (95% CI 0.8 - 1.0) for cereal fibre

(Aune et al., 2011). Whole grain foods are important sources of dietary fibre, and the

summary RR for CRC with an increment of three servings daily (90 g/day) of whole

grains was 0.8 (95% CI 0.8 - 0.9) (Aune et al., 2011). Proposed mechanisms for the

protective effects of fibre on CRC are increasing faecal bulk, diluting faecal

carcinogens, bacterial fermentation of fibre, and decreasing gut transit time (Aune et

al., 2011; Baena & Salinas, 2015). Other components of whole grains including

antioxidants, vitamins, trace minerals, phytate, phenolic acids, lignans, phytoestrogens,

folate, and magnesium may also have beneficial effects on reducing the risk of

developing CRC (Aune et al., 2011).

2.6 Histopathology

Table 2-2 shows the histological types of colorectal tumours according to the WHO

histological classification of tumours of the colon and rectum (Hamilton & Aaltonen,

2000). Adenocarcinoma is the most common CRC tumour type, accounting for 90%

of CRC (Resch, Schneider, & Langner, 2015). Mucinous adenocarcinomas constitute

4 -19 % of CRC (Langner et al., 2012) and are a subtype of adenocarcinomas that

secrete extracellular mucin (Resch et al., 2015). In Australia in the period 2006 - 2010,


28

the five-year survival from adenocarcinoma and mucinous adenocarcinoma was

similar (65% and 66%, respectively); survival was highest for adenocarcinoma in

tubulovillous adenoma and adenocarcinoma in adenomatous polyp (87% and 88%,

respectively), followed by adenocarcinoma in villous adenoma (79%) (Australian

Institute of Health and Welfare, 2012).

Table 2-2: WHO histological classification of tumours of the colon and rectum

Epithelial tumours Non-epithelial tumours

Adenoma Lipoma

Tubular Leiomyoma

Villous Gastrointestinal stromal tumour

Tubulovillous Leiomyosarcoma

Serrated Angiosarcoma

Intraepithelial neoplasia (dysplasia)

associated with chronic inflammatory

diseases

Kaposi sarcoma

Low-grade glandular intraepithelial

neoplasia

Malignant melanoma

High-grade glandular intraepithelial

neoplasia

Others

Carcinoma Malignant lymphomas

Adenocarcinoma Marginal zone B-cell lymphoma of

MALT Type

Mucinous adenocarcinoma Mantle cell lymphoma

Signet-ring cell carcinoma Diffuse large B-cell lymphoma

Small cell carcinoma Burkitt lymphoma

Squamous cell carcinoma Burkitt-like /atypical Burkitt-lymphoma

Adenosquamous carcinoma Others

Medullary carcinoma Secondary tumours

Undifferentiated carcinoma Polyps

Carcinoid (well differentiated endocrine

neoplasm)

Hyperplastic (metaplastic)

EC-cell, serotonin-producing neoplasm Peutz-Jeghers

L-cell, glucagon-like peptide and

PP/PYY producing tumour

Juvenile

Others

Mixed carcinoid-adenocarcinoma

Others

2.7 Cancer staging

Staging of CRC classifies the tumour according to the extent of disease spread, and

provides clinically useful prognostic information to assist in the clinical decision


29

making regarding optimal medical treatment for the disease (Australian Cancer

Network Colorectal Cancer Guidelines Revision Committee, 2005). In Australia, the

most common CRC staging systems are the Australian clinicopathological staging

(ACPS) (Table 2-3) (Davis, Evans, Cohen, & Theile, 1984; Davis & Newland, 1983),

Dukes staging system (Dukes, 1932) and tumour-node-metastasis (TNM)

classification (Table 2-4) (Obrocea, Sajin, Marinescu, & Stoica, 2011) (Table 2-5).

These classification systems take into account the depth of tumour through the

colorectal wall and the presence or absence of metastasis in regional lymph nodes

(Davis et al., 1984; Dukes, 1932; Martinez, Pitson, MacKinlay, & Cavedon, 2014).

The studies reported in this thesis use the TNM staging system to describe

participants.

Table 2-3: Australian clinicopathological staging

Stage A The carcinoma has spread into the bowel wall but not beyond the

muscularis propria. There are no lymph node metastases, nor distant

metastases.

Stage B The carcinoma has spread beyond the muscularis propria into the

adjacent tissues in continuity or into adjacent organs. There are no lymph

node metastases, nor distant metastases.

Stage C The carcinoma may have spread varyingly into or through the bowel

wall, but one or more lymph nodes contain cancer. There are no distant

metastases.

Stage D The carcinoma has spread beyond the lymph nodes to other areas, such as

the liver or lungs.

Table 2-4: TNM CRC staging

Primary tumour

(T)

TX Primary tumour cannot be assessed

T0 No evidence of primary tumour

Tis Carcinoma in situ: intraepithelial or invasion of lamina propria

T1 Tumour invades submucosa

T2 Tumour invades muscularis propria

T3 Tumour invades muscularis propria into pericolorectal tissues

T4a Tumour penetrates to the surface of the visceral peritoneum

T4b Tumour directly invades or is adherent to other organs or structures

Regional lymph


30

nodes (N)

NX Regional lymph nodes cannot be assessed

N0 No regional lymph node metastasis

N1 Metastasis in 1-3 regional lymph nodes

N1a Metastasis in 1 regional lymph node

N1b Metastasis in 2-3 regional lymph nodes

N1c Tumour deposit(s) in the subserosa, mesentery, or

nonperitonealized pericolic or perirectal tissues without regional

nodal metastasis

N2 Metastasis in 4 or more regional lymph nodes

N2a Metastasis in 4-6 regional lymph nodes

N2b Metastasis in 7 or more regional lymph nodes

Distant

metastasis (M)

M0 No distant metastasis (no pathologic M0; use clinical M to complete

stage group)

M1 Distant metastasis

M1a Metastasis confined to 1 organ or site (e.g., liver, lung, ovary,

nonregional node)

M1b Metastases in more than 1 organ/site or the peritoneum

Table 2-5: TNM, Duke and ACPS cancer staging for CRC

ACPS / Duke

stage

TNM stage T N M

0 Tis N0 M0

A I T1 N0 M0

T2 N0 M0

B IIA T3 N0 M0

IIB T4a N0 M0

IIC T4b N0 M0

C IIIA T1–T2 N1/N1c M0

T1 N2a M0

IIIB T3–T4a N1/N1c M0

T2–T3 N2a M0

T1–T2 N2b M0

IIIC T4a N2a M0

T3–T4a N2b M0

T4b N1–N2 M0

D IVA Any T Any N M1a

IVB Any T Any N M1b

Survival of CRC is progressively worse with increased stage of disease. In Australia,

the one-year net survival for patients with colon cancer is 95% for localized stage

(stage I and II), 87% for regional stage (stage III), and 43% for distant stage (stage IV)

(Walters et al., 2013); the one-year survival rate is similar for patients with rectal


31

cancer, with 94% for localized stage, 91% for regional stage and 52% for distant stage

(Maringe et al., 2013).

2.8 Signs and symptoms of CRC at diagnosis

Abdominal pain, change in bowel habit, and rectal bleeding are the three most

commonly reported symptoms of CRC (Ballinger & Anggiansah, 2007; Bazensky,

Shoobridge-Moran, & Yoder, 2007; John, George, Primrose, & Fozard, 2011). Other

signs and symptoms of CRC include constant back pain, unusual gas or bloating,

unexplained weight loss, fatigue, anaemia and vomiting (Bazensky et al., 2007; John

et al., 2011). These signs and symptoms are also common in other gastrointestinal

conditions, hence the symptom that is often first recognized by patients is blood in the

stool (Bazensky et al., 2007). In Australia, approximately 83% of patients present

electively with symptoms of rectal bleeding, weight loss and change in bowel habit,

and 11% present with emergency symptoms of massive haemorrhage and bowel

obstruction (McGrath et al., 2004). A previous systematic review has reported the

associations of the commonly reported or presented signs, symptoms, and clinical

features with the risk of CRC; the clinical features with a positive predictive value (i.e.

the probability that the disease is truly present when the test result is positive) > 10%

are palpable rectal or abdominal mass; rectal bleeding combined with weight loss;

iron deficiency anaemia; rectal bleeding mixed with stool; rectal bleeding in the

absence of perianal symptoms; rectal bleeding combined with change in bowel habits

(Del Giudice et al., 2014). The presence of these signs/symptoms warrants further

investigation in diagnosing CRC. Moreover, some of these symptoms may persist

after cancer treatment and significantly impact on the patient’s daily functioning and

HRQoL. Therefore, it is important to understand the natural history of physical and

psychological symptoms in patients undergoing CRC surgery in order to develop

appropriate interventions to address these de novo or residual symptoms for patients

with CRC.


32

2.9 Treatment

2.9.1 Overview of CRC treatment

Colorectal cancer can be treated medically with a combination of surgery, RT, CT,

and or targeted therapy. Depending on the stage and location of the cancer, either one

or a combination of these treatments may be offered. According to the National

Comprehensive Cancer Network (NCCN) guidelines (National Comprehensive

Cancer Network (NCCN), 2016a, 2016b), surgery is recommended for resectable

stage I, II and III CRC (National Comprehensive Cancer Network (NCCN), 2016a,

2016b). After surgery, adjuvant (additional) treatment may be offered to patients with

stage II and III CRC if the cancer is likely to return (National Comprehensive Cancer

Network (NCCN), 2016a, 2016b). Neoadjuvant (preoperative) treatment is also

available for patients with stage IIIC (T4b) colon cancer (National Comprehensive

Cancer Network (NCCN), 2016a) and stage II and III rectal cancer (National

Comprehensive Cancer Network (NCCN), 2016b). A combination of surgery and CT,

CT with or without targeted therapy, and surgery plus CT with or without targeted

therapy are the treatment options for patients with stage IV CRC (National

Comprehensive Cancer Network (NCCN), 2016a, 2016b).

2.9.1.1 Surgical approaches for CRC

The aims of surgery are to cure and to avoid recurrence (Dorudi, Steele, & McArdle,

2002). Surgical resection is one of the most common treatments for CRC with a rate

of surgery ranging from 54% to 85%, depending on cancer site, stage, and patient age

(Chawla et al., 2013) and results in cure in approximately 50% of patients (Labianca

et al., 2010). In Australia, about 82% of patients undergo surgery with curative intent

(McGrath et al., 2004). However, the types of surgery used to treat colon and rectal

cancers are slightly different (Tamas et al., 2015).


33

Colon cancer surgery

In colon cancer surgery, the tumour and the corresponding lymph vessels are removed

by colectomy (sometimes called a hemicolectomy, partial colectomy, or segmental

resection) with lymphadenectomy (Brenner et al., 2014; National Comprehensive

Cancer Network (NCCN), 2016a). The extent of surgery is based on the tumour

location and the supplying blood vessels containing the regional lymph node

(National Comprehensive Cancer Network (NCCN), 2016a). If the surgery is

performed through a single incision in the abdomen, it is referred to as an open

colectomy (McKenzie et al., 2005). Right hemicolectomy, transverse colectomy, left

hemicolectomy, and total colectomy are the most common surgical procedures for

colon cancer (Figure 2.5) (De Rosa et al., 2015; McKenzie et al., 2005). Recently,

minimally invasive procedures (i.e. laparoscopic-assisted colectomy) have been

utilized as an alternative approach to removing part of the colon and nearby lymph

nodes by making several smaller incisions instead of one long incision in the

abdomen (Porpiglia & Sigurdson, 2015). A meta-analysis by Di et al. has suggested

that laparoscopic colectomy is as effective and as safe as open colectomy in terms of

the overall mortality (RR = 0.9), total recurrence rate (RR = 0.9), 5-year tumour free

survival rate (RR = 1.0), and overall 5-year survival (RR =1.0) (Di et al., 2013). The

overall mortality in laparoscopic colectomy and open colectomy is 25% to 26%; the

total recurrence rates are 19% to 20%; the 5-year tumour free survival rate is 62%;

and the overall 5-year survival rates are 74% to 75% (Di et al., 2013).


34

Figure 2.5: Surgical procedures for colon cancer: (A) right hemicolectomy; (B)

transverse colectomy; (C) left hemicolectomy; (D) total colectomy (Cancer Council

Victoria, 2013).

Rectal cancer surgery

Rectal cancer has been defined as a tumour located within 12 cm of the anal verge

(National Comprehensive Cancer Network (NCCN), 2016b). The treatment of rectal

cancer is more complicated and aggressive than that for colon cancer due to the

location (narrow pelvis) and the vital structures (large vessels, nerves, bladder,

internal genital organs or sacrum) surrounded the rectum (Tamas et al., 2015).

Therefore, the additional aims of rectal cancer surgery are to avoid autonomic nerve

dysfunction and permanent colostomy and to maintain adequate anorectal function

(Dorudi et al., 2002). The surgical procedures for rectal cancer can be classified as

local procedures including polypectomy, transanal excision, and transanal endoscopic

microsurgery (TEM); and procedures involving a transabdominal resection, such as

(A)

(B) (C) (D)

Descending colon

Transverse colon

Ascending colon

Caecum

Sigmoid colon

Rectum


35

high anterior resection (HAR) (Figure 2.6 A), low anterior resection (LAR), ultra-low

anterior resection (ULAR) (Figure 2.6 B), proctectomy with total mesorectal excision

(TME) and coloanal anastomosis, and abdominoperineal resection (APR) (Figure 2.6

C) (Brenner et al., 2014; National Comprehensive Cancer Network (NCCN), 2016b).

Figure 2.6: Surgical procedures for rectal cancer: (A) high anterior resection; (B)

ultra-low anterior resection; (C) abdominoperineal resection (Cancer Council Victoria,

2013).

The treatment of rectal cancer is heavily stage dependent (Porpiglia & Sigurdson,

2015). For stage I rectal cancer, local excision (i.e. transanal excision and TEM) can

be used (American Cancer Society, 2014). For most stage II or III rectal cancers, LAR

could be considered if the cancer is in the upper third of the rectum (American Cancer

Society, 2014); and the LAR is recommended to extend 4 to 5cm below the distal of

the tumour using TME followed by a colorectal anastomosis (National

Comprehensive Cancer Network (NCCN), 2016b). When the stage II or III rectal

cancer is in the middle and lower third of the rectum, proctectomy with TME and

coloanal anastomosis is required (American Cancer Society, 2014).

Abdominoperineal resection is considered when stage II or III rectal cancer is in the

lower third of the rectum and when the cancer is growing into the sphincter muscle

(American Cancer Society, 2014). As the anal sphincters are resected en bloc with

APR, a permanent colostomy is required (Damin & Lazzaron, 2014). As the goal of

rectal cancer surgery is to maintain anorectal function, sphincter-saving or sphincter

preservation surgery, which includes intersphincteric resection or ultra-LAR and

coloanal anastomosis, should be recommended if possible to patients with ultralow

tumours (< 1 cm from the dentate line or within 6 cm from the anal verge) (Damin &

(A) (B) (C)


36

Lazzaron, 2014; Porpiglia & Sigurdson, 2015). Colostomy or ileostomy is required if

creation of an anastomosis is not possible (National Comprehensive Cancer Network

(NCCN), 2016b). Colostomy/ileostomy can be permanent or temporary; if the ostomy

is temporary, the reversal is usually undertaken within 8 to 12 weeks after the primary

rectal resection (Damin & Lazzaron, 2014).

An Australian survey has shown that anterior resection is the most common procedure,

with approximately 61% of patients with rectal cancer undergoing an anterior

resection (McGrath et al., 2004) in 2000. About 24% of patients received APR, and

TME was used in 65% of patients with rectal cancer (McGrath et al., 2004). In

Victoria, the overall rate of anterior resection was 53%; APR was 23%; ultra-LAR

was 23%; total proctocolectomy 1.2%; and TEM was 0.2% in 2005 (Marwan, Staples,

Thursfield, & Bell, 2010).

Similar to colon cancer surgery, surgery for rectal cancer can be performed

laparoscopically or open (De Rosa et al., 2015). Meta-analyses have found no

significant differences in postoperative complications, oncological clearance, local

and distant recurrences, disease-free survival and overall survival between

laparoscopic and open surgery for rectal cancer (Jiang et al., 2015; Zhang et al., 2014),

which suggest that laparoscopic surgery is comparable to open surgery for treatment

of rectal cancer. The 5-year or longer time overall survival and disease-free survival

are similar for open surgery (65% and 67%) and for laparoscopic surgery (63% and

69%) (Zhang et al., 2014).

Although surgery is the mainstay of treatment for CRC, it is associated with

postoperative complications and morbidity (van Vugt, Reisinger, Derikx, Boerma, &

Stoot, 2014). In Australia, the average length of stay in hospital is 10 days after CRC

surgery (Rothwell, Bokey, Keshava, Chapuis, & Dent, 2006). Approximately 11% of

patients have a CRC surgery-related post-operative complication (i.e. wound infection,

deep venous thrombosis, pulmonary embolus, anastomotic leak. Wound infection is

the most commonly reported (7.4%) complication and anastomotic leak is the second

most commonly reported complication (2.1%) (McGrath et al., 2004). Postoperative


37

complications are classified as infective or non-infective. Infective complications

include wound infection, anastomotic leakage, Intra-abdominal collection, pneumonia,

septicaemia, and urinary tract infection (McSorley, Horgan, & McMillan, 2016).

Non-infective complications are seroma, dehiscence, haemorrhage, myocardial

infarction, arrhythmia, venous thromboembolism, cerebrovascular accident, renal

failure, acute urinary retention, and ileus (paralytic/non-mechanical small bowel

obstruction) (McSorley et al., 2016). McSorley et al. has reported that infective

complications have a detrimental impact on disease free and overall survival (hazard

rate = 1.4, 95%CI 1.1 - 1.8; hazard rate = 1.4, 95%CI 1.2 - 1.6) (McSorley et al.,

2016). Furthermore, open CRC surgery is associated with high levels of postoperative

fatigue, malnutrition (Garth, Newsome, Simmance, & Crowe, 2010), and a significant

reduction in physical performance, work capacity, muscle strength and lean body

mass (Jensen et al., 2011). Postoperative complications and morbidity have adverse

effects on HRQoL, particularly physical functioning, role functioning, social

functioning, body image, mobility, self-care, and pain/discomfort after curative CRC

surgery (Brown et al., 2014) which are detrimental to the patient. Post-operative

impairments and recovery following CRC in patient outcomes are investigated further

in Study 3 in this thesis.

2.9.2 Adjuvant medical treatment (radiotherapy and chemotherapy)

Neoadjuvant therapy

Neoadjuvant therapy (i.e. pre-operative RT with or without CT) is recommended by

the NCCN guideline for stage II and III rectal cancer (National Comprehensive

Cancer Network (NCCN), 2016b). Neoadjuvant therapy followed by radical resection

and subsequent adjuvant CT is standard care for patients with locally advanced rectal

cancer (Sclafani & Chau, 2016). Neoadjuvant treatment is also an option for patients

with resectable T4b colon cancer (National Comprehensive Cancer Network (NCCN),

2016a). However, neoadjuvant therapy is not recommended for patients with stage I

CRC given the low recurrence rate (about 3%) and small benefits (Brenner et al.,

2014). The role of the neoadjuvant RT is to inhibit cell proliferation and tumour


38

growth and to induce apoptotic cell death (Hendry & West, 1997). The potential

effects of a combination of neoadjuvant RT with CT are to sensitize local RT, to

induce tumour downsizing, to improve rates of sphincter preservation, and to increase

rates of pathological complete response (Gaertner, Kwaan, Madoff, & Melton, 2015).

In Australia, about 72% of patients with rectal cancer have received neoadjuvant RT

(McGrath et al., 2004). Although neoadjuvant therapy improves oncologic outcomes

(survival and recurrence rates) for patients with rectal cancer, it is associated with

treatment-related toxicity (Joye & Haustermans, 2014; National Comprehensive

Cancer Network (NCCN), 2016b); high rates of morbidity, such as impaired bowel

and sexual function, malnutrition, and reduced physical fitness (Gavaruzzi, Lotto,

Giandomenico, Perin, & Pucciarelli, 2014; West et al., 2014; Yamano et al., 2016);

and decreased HRQoL (Battersby et al., 2016). A systematic review by Gavaruzzi et

al. found that neoadjuvant therapy has a detrimental impact on bowel and sexual

function but less significant impact on bladder function (Gavaruzzi et al., 2014).

Adjuvant therapy

Adjuvant CT is recommended for all patients with stage II and III rectal cancer

(National Comprehensive Cancer Network (NCCN), 2016b), and patients with stage

III or stage II colon cancer with a high risk of relapse (Brenner et al., 2014). In

Australia, adjuvant CT is received by 29% of stage II colon cancer and 47% of stage

II rectal cancer, and 76% of stage III colon cancer and 90% of stage III rectal cancer

(McGrath et al., 2004). Chemotherapy regimen involving infusional 5-FU with

leucovorin (folinic acid) is the standard of care for patients with CRC (Gustavsson et

al., 2015), and a combination of CT regimen (Oxaliplatin/5-FU/Leucovorin) called

FOLFOX has been shown to further enhance the treatment (Brezden-Masley &

Polenz, 2014).

Despite the survival benefits of adjuvant CT, toxicities of the CT can significantly

impact on patient’s HRQoL (Mols et al., 2015). These include nausea, diarrhoea,

myelosuppression, fatigue, palmar-plantar syndrome (hand-foot syndrome),


39

peripheral neuropathy, and hypersensitivity (Aprile, Rihawi, De Carlo, & Sonis, 2015;

Goodwin & Asmis, 2009; Park et al., 2013; Tantoy, Cataldo, Aouizerat, Dhruva, &

Miaskowski, 2016). During CT, the most common physical and psychological

symptoms experienced by more than 40% of patients with CRC are

numbness/tingling in the hands/feet (64%), lack of energy (62%), feeling drowsy

(49%), nausea (45%), shortness of breath (43%), dry mouth (42%) difficulty sleeping

(46%) and worrying (44%) (Pettersson, Bertero, Unosson, & Borjeson, 2014). A

previous study has also shown that patients treated with CT who are not meeting the

PA guidelines of 150 min of moderate to vigorous PA per week experience higher CT

related toxicities (Mols et al., 2015).

In Australia, about 17% of patients with CRC present with a metastasis at the time of

diagnosis (McGrath et al., 2004). The main goals of treatment for stage IV CRC are to

prolong survival, to cure, to stop tumour progression, to improve cancer-related

symptoms, and to maintain HRQoL (Labianca et al., 2010; Van Cutsem, Cervantes,

Nordlinger, Arnold, & Group, 2014). Treatment options include surgical resection of

primary tumour, surgical resection of the metastases (liver or lung), palliative CT,

palliative RT, and targeted therapy (Labianca et al., 2010).

Targeted therapy

Biologic or targeted agents, such as monoclonal antibodies (cetuximab and

panitumumab) that inhibits epidermal growth factor receptor; a monoclonal antibody

(bevacizumab) and proteins (aflibercept) against vascular endothelial growth factor;

and a multi-kinase inhibitor (regorafenib), are used in combination with CT in

patients with stage IV CRC (Aparo & Goel, 2012; Fakih, 2015). The overall survival

in patients who have received targeted therapy ranges from 6 months to 26 months,

which is worse than curative treatment (Rolfo et al., 2014). Regardless of the survival

benefits from the introduction of targeted therapy (Kirstein et al., 2014), treatment of

stage IV CRC should be personalized depending on the age of patient, patient’s

molecular phenotype, comorbidities, performance status, extent of the disease, and


40

goals of treatment (Brenner et al., 2014; Fakih, 2015; Van Cutsem et al., 2014). Table

2-6 summarizes the most common symptoms or side effects from cancer treatment.

Table 2-6: Most common symptoms or side effects from cancer treatment

Cancer treatment Symptoms or side effects

Surgery Adhesions

Faecal incontinence

Sexual dysfunction

Wound infection

Deep venous thrombosis

Pulmonary embolus, anastomotic leak

Chemotherapy Fatigue

Hair loss

Increased risk of infection / fever

Diarrhoea

Neuropathy & nerve changes

Mouth sores (mucositis)

Hand-foot syndrome

Nausea and vomiting

Myelosuppression

Radiotherapy Faecal incontinence & adhesions

Skin irritation

Nausea

Rectal irritation

Faecal incontinence

Bladder irritation

Fatigue/tiredness

Sexual problems

Reduced physical fitness

Targeted therapy Skin toxicity


41

2.10 Side effects and symptoms following treatment

Patients with stage I-III CRC experience symptoms associated with their disease,

treatment, and comorbidities (Deshields, Potter, Olsen, Liu, & Dye, 2011). Research

has shown that patients with CRC 6 to 8 months following initial diagnosis report an

average of 12 symptoms (Deshields et al., 2011). Overall, lack of energy was the most

prevalent symptom for CRC, which was experienced by 79% of patients with CRC

(Deshields et al., 2011). In addition to the symptoms, comorbidity is also common

among patients with CRC; hypertension, diabetes, and cardiovascular diseases are the

most prevalent comorbodities (van Leersum et al., 2013). Symptoms and

comorbidities can significantly impact upon patients’ activities of daily living, reduce

their functional status, and decrease their HRQoL (Cheng & Lee, 2011). Based on the

ICF model, Bours et al. have identified potential predictors of low HRQoL in CRC

survivors (Bours et al., 2016), which include the presence of a stoma and comorbidity

(ICF domain: health condition); high BMI, high levels of fatigue, psychological

distress, anxiety, and depression (ICF domain: body structures/functions); low levels

of PA (ICF domain: activities); low perceived social support, and low perceived

quality of care (environmental factors); low optimism and negative cancer threat

appraisal (personal factors). The most common symptoms experienced by the patients

following CRC treatment are described below.

2.10.1 Pelvic floor dysfunction

Pelvic floor dysfunction refers to a wide variety of clinical conditions, including

bladder, bowel, and sexual dysfunction (Sung & Hampton, 2009).

Bowel function and symptoms

Bowel symptoms are common in the general population (Kepenekci et al., 2011). The

prevalence of faecal incontinence is 8% (male 8% and female 9%) in the community

(Ng, Sivakumaran, Nassar, & Gladman, 2015). Bowel symptoms or dysfunction,

including diarrhoea, abdominal pain, an alteration in the frequency of bowel


42

movements, incontinence, abnormal sensations, and difficulties with evacuation, are

commonly reported among CRC survivors (Kent, Mitchell, Oakley-Girvan, & Arora,

2014), and most of these symptoms are frequent and severe within the first year

following rectal cancer surgery, especially within the first six months, and stabilize

after one year though some may persist for years (Lai, Wong, & Ching, 2013).

Surgical treatment may damage anal sphincter or levator ani muscles and alter bowel

function in patients who have undergone surgery for rectal cancer (Hirano, Koda,

Kosugi, Yamazaki, & Yasuda, 2011; Koda et al., 2009; van Duijvendijk et al., 2003).

Bowel symptoms are commonly reported among patients undergoing LAR for rectal

cancer 8 to 16 months postoperatively, with 63% experienced incontinence of flatus,

42% incontinence of liquid stool, and 14% incontinence of solid stool (Lin, Chen, &

Liu, 2015). Bowel dysfunction after rectal cancer treatment is closely related to

tumour height, which determines preservation of the anal sphincters and rectal

capacity; pouch reconstruction; and RT (Fish & Temple, 2014).

While it is widely recognized that bowel dysfunction is more prevalent and severe in

patients following rectal cancer surgery than patients with colon cancer (Fish &

Temple, 2014; Scheer et al., 2011; van Duijvendijk et al., 2003), small studies have

documented that patients who have undergone surgery for colon cancer also

experience changes in bowel habits and other bowel problems (Phipps et al., 2008;

Thorsen et al., 2016). A study by Nikoletti et al. which included both colon and rectal

cancer cohorts reported that incomplete evacuation (75.2%), excessive flatus (75.2%),

urgency (73.3%), straining (61.4%), perianal soreness or itching (49.5%), bloating

(43.6%), and faecal incontinence (37.6%) are the most frequently reported bowel

symptoms in patients 6 to 24 months after surgery for CRC (Nikoletti et al., 2008).

Neoadjuvant chemoradiotherapy has also been documented to cause adverse effects

on bowel function by vascular toxicity and damage to the anal sphincter muscle,

which may lead to a decrease in anal resting pressure and colonic compliance and

inhibition of the impulse conduction (Knowles et al., 2013; Ozgen et al., 2015). Rectal

cancer surgery (i.e. TME) is probably the main contributing factor to major LAR


43

syndrome, a constellation of symptoms including faecal urgency, frequent bowel

movements, bowel fragmentation and incontinence (Ziv, Zbar, Bar-Shavit, & Igov,

2013), with preoperative RT and age > 75 years conferring further risks (Chen et al.,

2015). Two systematic reviews have concluded that TME and preoperative RT have

negative impact on long-term bowel function (Loos et al., 2013; Scheer et al., 2011).

Bowel dysfunction and symptoms following cancer treatment can lead to alterations

in daily activities, work, social relationships, and impact the patients’ HRQoL (Bailey

et al., 2015; Varpe et al., 2011).

Bladder function and symptoms

Bladder dysfunction is a common problem within the general population, and the

prevalence is lower in males (13% - 28%) (Martin et al., 2011) than in females (32% -

66%) (Teleman, Lidfeldt, Nerbrand, Samsioe, & Mattiasson, 2005), as vaginal

delivery and parity increase the risk of urinary symptoms in women (Kepenekci et al.,

2011; Lukacz, Lawrence, Contreras, Nager, & Luber, 2006). Bladder dysfunction and

symptoms include urinary incontinence, urgency and frequency, slow or intermittent

stream and straining, and feeling of incomplete emptying (Messelink et al., 2005);

among which, urinary incontinence is the main focus in the literature. Approximately

1% to 39% of male and 37% to 55% of female in general population experience

urinary incontinence (Tikkinen, Agarwal, & Griebling, 2013; Wood & Anger, 2014).

Although bladder dysfunction after CRC treatment remains poorly understood (Fish

& Temple, 2014), it is a significant clinical problem and has been shown to be related

to surgical nerve damage in rectal cancer (Lange et al., 2008). While bladder

symptoms are transient and less frequently reported (10.3%) in patients following

colon cancer treatment (Fish & Temple, 2014; Tomoda & Furusawa, 1985), patients

following rectal cancer surgery often experience worse bladder symptoms compared

to preoperative levels (Daniels, Woodward, Taylor, Raja, & Toomey, 2006). One

study has shown bladder symptoms developed following surgery for rectal cancer in

females included nocturia (59%) and stress incontinence (18%), and 80% of these

symptoms persisted longer than three months from surgery (Daniels et al., 2006).

Urgency and incontinence are the most frequent bladder symptoms reported in 77%


44

and 63% of patients who have undergone APR or LAR for rectal cancer (Bregendahl,

Emmertsen, Lindegaard, & Laurberg, 2015). Neoadjuvant RT for rectal cancer has

also been shown to be associated with voiding difficulties (odds ratio [OR] = 1.6,

95% CI 1.1 - 2.4) (Bregendahl et al., 2015). To date, post-operative bladder

dysfunction is prevalent in patients after rectal cancer treatment, however there is

limited evidence on bladder symptoms in patients following colon cancer treatment.

More research on changes in bladder symptoms in patients undergoing colon cancer

surgery is warranted.

Sexual function and symptoms

There is a limited number of studies evaluating sexual dysfunction in the community

(McCool, Theurich, & Apfelbacher, 2014). Among females, sexual dysfunction

includes hypoactive sexual desire disorder, sexual arousal disorder, orgasm disorder,

and pain disorders (Giraldi et al., 2011). The prevalence rates of sexual dysfunction in

females varies widely in the literature, with the prevalence of female arousal disorder

ranging from 11% to 48% (McCool et al., 2014), hypoactive sexual desire disorder

3% to 10% (Davison, 2012; McCabe & Goldhammer, 2013) and pain disorders 6.5%

to 45% (Boa, 2013). In males, sexual dysfunction can be classified into erectile

dysfunction and ejaculatory disorders such as premature ejaculation (Jannini, Maggi,

& Lenzi, 2011). The prevalence rates of erectile dysfunction and premature

ejaculation are about 34% and 30% respectively (Lee, Fahmy, & Brock, 2013).

The rates of sexual dysfunction can be high in patients with CRC given the

physiological changes following cancer treatment (Averyt & Nishimoto, 2014).

Similar to bladder dysfunction, sexual dysfunction after CRC treatment also remains

poorly understood due to insufficient measurement of preoperative function and

psychosocial confounders (Fish & Temple, 2014). Nevertheless, to date it appears that

both men and women experience sexual dysfunction after rectal cancer surgery

(Angenete, Asplund, Andersson, & Haglind, 2014). Following surgery for rectal

cancer, sexual function is worse in 23% to 69% of men and 19% to 62% of women

(Ho, Lee, Stein, & Temple, 2011). Moreover, rates of erectile dysfunction (54%


45

versus 25%) and ejaculation problems (68% versus 47%) are higher in male patients

with rectal cancer than those with colon cancer (Den Oudsten et al., 2012). Females

with rectal cancer have reported more vaginal dryness (35% versus 28%) and pain

during intercourse (30% versus 9%) than those with colon cancer (Den Oudsten et al.,

2012). Neoadjuvant RT, a stoma, complications during or after surgery, a higher age,

type of surgery, and a lower tumour location are the predictors of postoperative sexual

dysfunction in patients with CRC (Traa, De Vries, Roukema, & Den Oudsten, 2012).

As most of the existing studies on sexual dysfunction following CRC surgery suffer

from low methodological quality (i.e. cross-sectional design, small sample size, and

the use of nonstandardized measurements) (Traa et al., 2012), more well designed

research is needed to understand the natural history of sexual dysfunction in patients

undergoing CRC surgery before an appropriate intervention can be developed to

address this important issue in the CRC populations.

2.10.2 Physical function (functional exercise capacity and muscle strength)

Functional exercise capacity is defined as the maximal performance in a given

physical domain and is an important measure of an individual’s ability to achieve

essential tasks needed in daily living (Larson, 2007; Matheson, 1996). Functional

exercise capacity can be measured directly by determining peak oxygen consumption

(VO2max), estimated from the highest treadmill or cycle work rate achieved, or

measured using submaximal testing, such as timed field walking tests (Fleg et al.,

2000). Patients with stage I-II CRC have significantly lower functional exercise

capacity measured by 6MWT (325 meters) compared to a healthy control group

(6MWT distance = 469 meters) 6 months following completion of cancer treatment

(Sanchez-Jimenez et al., 2015). A pre-operative 6MWT distance shorter than 392

meters is predictive of cardiopulmonary complications for colorectal surgery patients

(Li et al., 2013). Moreover, neoadjuvant chemoradiotherapy has been shown to be

associated with a clinically significant reduction in VO2max (West et al., 2014).

Functional exercise capacity is a common target for exercise and physiotherapy

interventions in CRC as higher functional exercise capacity is associated with a lower


46

risk of cancer mortality and cardiovascular disease mortality following a diagnosis of

CRC (Lakoski et al., 2015). Moreover, exercise and PA has numerous documented

health-benefits among cancer survivors, including improved disease-free survival,

functional exercise capacity, muscular strength, and HRQoL (Brown, Winters-Stone,

Lee, & Schmitz), which is discussed in further detail later in the thesis.

Muscle strength refers to the maximal voluntary force or torque of short duration that

skeletal muscles can bring to bear on the environment (Bohannon, 2015). Grip

strength measured by dynamometry has been shown to reflect overall muscle strength

and physical performance particularly among older adults (Bohannon, Magasi, Bubela,

Wang, & Gershon, 2012; Kim et al., 2016) and is highly predictive of survival

(Bohannon, 2015). The normative values of grip strengths for individuals living in the

community are 28kg (female) and 47kg (male) for individuals aged 51 to 60 years,

and 26kg and 42kg for females and males aged 61 to 70 years (Leong et al., 2016). A

previous study has shown that the hand grip strength in a group of stage II-III CRC

patients (average age 56 years) who completed treatment within 2 years was 24kg in

females and 40kg in males (Ahn et al., 2016). Furthermore, sarcopenia defined as

reduced skeletal muscle mass plus low muscle strength and/or low physical

performance is highly prevalent among older patients with early stage CRC (56% -

60%) (Broughman et al., 2015). Sarcopenia is an independent risk factor for

complications after surgery for CRC (Huang et al., 2015) and a predictor for worse

overall survival in patients who have undergone an elective open colon resection for

CRC (hazard ratio = 8.54, 95% CI 1.07 - 68.32) (Boer et al., 2016). Resistance

training has been shown to be associated with clinically positive effects on muscle

strength in cancer survivors (Strasser, Steindorf, Wiskemann, & Ulrich, 2013);

therefore, international guidelines recommend CRC survivors to do strength exercises

at least 2 days per week in addition to at least 150 min of aerobic exercises per week

(El-Shami et al., 2015).

2.10.3 Level of physical activity


47

According to the WHO, PA is defined as any bodily movement produced by skeletal

muscles that requires energy expenditure (World Health Organization, 2010). The

WHO guidelines recommend that adults aged 65 years and above should do at least

150 minutes of moderate-intensity aerobic PA throughout the week or at least 75

minutes of vigorous-intensity aerobic PA throughout the week or an equivalent

combination of moderate- and vigorous-intensity activity, undertake muscle

strengthening activities involving major muscle groups on 2 or more days a week; and

avoid sedentary time (World Health Organization, 2010). The PA guidelines

specifically for patients with cancer and cancer survivors are the same (Buffart,

Galvao, Brug, Chinapaw, & Newton, 2014; El-Shami et al., 2015; Rock et al., 2012).

Previous studies have reported that CRC survivors are less likely to meet the PA

recommendations than their healthy peers (Chung et al., 2013; Grimmett, Bridgewater,

Steptoe, & Wardle, 2011; Hawkes et al., 2008). A study by Chung et al. found that

patients with CRC tend not to participate in the recommended levels of PA during

treatment (meeting the guideline: 20% pre-diagnosis; 7.6% during treatment) (Chung

et al., 2013). Furthermore, an Australian survey among CRC survivors demonstrated

that CRC survivors were more likely to be insufficiently active (1–149 min per week)

and inactive (0 min per week) compared to a non-cancer population; the percentage of

survivors who were sufficiently active reduced from 53% pre-diagnosis to 32% at 6

months and 38% at 12 months post-diagnosis (Hawkes et al., 2008). At 12 months,

CRC survivors were more likely than a matched population group to be insufficiently

active (OR = 1.6, 95% CI 1.3 - 1.8) (Hawkes et al., 2008). The most commonly

reported barriers to PA in patients with CRC are related to cancer and its treatments

(e.g. fatigue), age and mobility-related comorbidities (e.g. impaired mobility) (Fisher

et al., 2016).

In CRC, sedentary behaviour is associated with poorer overall and disease specific

survival, with higher all-cause mortality when spending 6 or more hours per day of

leisure time sitting compared with fewer than 3 hours per day (prediagnosis sitting

time: RR = 1.4; 95% CI 1.1 - 1.7; postdiagnosis sitting time: RR = 1.3; 95% CI, 1.0 -

1.6) (Campbell, Patel, Newton, Jacobs, & Gapstur, 2013). Conversely, increased PA


48

is associated with improved prognosis and HRQoL (Otto et al., 2015). A

meta-analysis estimated that each 10 MET - hour per week increase in PA after CRC

diagnosis (i.e. 150 minute of moderate intensity activity per week) is associated with a

28% lower total mortality risk in CRC survivors (Schmid & Leitzmann, 2014).

Despite that PA levels of CRC survivors have been documented across the cancer

continuum, it remains unknown how PA levels change in relation to the CRC surgery

in Australia.

2.10.4 Anxiety and depression

The prevalence rate of anxiety and depression among the general Australian

population are 20% and 6% respectively (Chiu, 2004; McEvoy, Grove, & Slade,

2011).The diagnosis of cancer is a highly distressing experience for most patients and

their families due to the uncertainties related to cancer prognosis and the possibility of

death (Graca Pereira, Figueiredo, & Fincham, 2012). While anxiety rates in patients

with CRC are similar to the general population, depression rates are higher in patients

with CRC (19% for anxiety and 37% for depression) than the general population

(Simon, Thompson, Flashman, & Wardle, 2009; Tsunoda et al., 2005). Anxiety and

depression have been shown to be different in patient with CRC according to the

treatment approaches and disease stage (Graca Pereira et al., 2012). Patients who have

undergone surgery and CT or RT have significantly more anxiety and depression

compared to the surgery only group (Graca Pereira et al., 2012; Medeiros, Oshima, &

Forones, 2010). Patients with more advanced disease (stage III and IV) are more

anxious and depressed than those with localized disease (Simon et al., 2009).

However, a study by Russel et al. reported that CRC survivors who have completed

treatment within 6 months have lower levels of anxiety and depression compared to

community norms (Russell et al., 2015). The inconsistency in the literature warrants

further research to explore this issue. Nevertheless, research has shown that anxiety

and depression are strong predictors of HRQoL in patients with CRC (Graca Pereira

et al., 2012; Tung et al., 2016). Moreover, one study has shown that depressive

symptoms increase the risk of mortality among 1- to 2-year CRC survivors and 1- to


49

10-year CRC survivors (hazard ratio = 2.6, 95 % CI 1.4 - 4.5; hazard ratio = 1.9, 95 %

CI 1.2 - 2.8) (Mols, Husson, Roukema, & van de Poll-Franse, 2013).

2.10.5 Health-related quality of life (HRQoL)

Health-related quality of life refers to the physical, emotional and social aspects of

quality of life that are influenced by disease or treatment (Kaplan & Ries, 2007).

Symptoms, surgical procedures, and the number of comorbidities can significantly

affect HRQoL in patients with CRC (Marventano et al., 2013). A study has shown

that CRC survivors who have completed treatment within 6 months still experience

lower role, cognitive and social functioning, and higher fatigue, nausea/vomiting,

appetite loss, diarrhoea, financial problems, pain, and constipation than community

norms (Russell et al., 2015). Nevertheless, a previous study has shown that HRQoL in

patient with CRC is quite satisfactory one year after the surgery (Di Fabio, Koller,

Nascimbeni, Talarico, & Salerni, 2008) despite that patients undergoing surgery for

rectal cancer tend to have more bowel-related HRQoL problems than those

undergoing surgery for colon cancer (Di Fabio et al., 2008). Health-related quality of

life is also poor in patients with a permanent stoma following APR (Konanz, Herrle,

Weiss, Post, & Kienle, 2013). Research has shown that post-operative pelvic floor

dysfunction was associated with an impaired HRQoL (Pucciarelli et al., 2011; Taylor

& Morgan, 2011; Varpe et al., 2011). The presence of a stoma, comorbidity, high

BMI, high levels of fatigue, psychological distress, anxiety, depression, low levels of

PA, low perceived social support, and shorter time since diagnosis are the potential

predictors of low HRQoL in CRC survivors (Bours et al., 2016). Furthermore,

financial stress is strongly associated poorer HRQoL and may prevent adherence to

recommended treatments (Regenbogen et al., 2014) and thereby compromise

treatment outcomes. Therefore, understanding the symptoms and comorbidities

experienced by CRC survivors is essential for implementing appropriate supportive

care interventions with a particular focus on decreasing symptoms and improving

patients’ HRQoL.


50

Studies have found that HRQoL has an independent prognostic value in predicting

mortality in patients with CRC (Fournier et al., 2016; Wong, Law, Wan, Poon, & Lam,

2014). Moreover, Fournier et al. reported that patients with role functioning scores

lower than the median had a 5-year relative survival of 49% compared with 80% for

patients with role functioning scores higher than the median (hazard ratio = 3.1)

(Fournier et al., 2016). Given the close relationships between HRQoL and survival,

symptom management and HRQoL improvement are important goals in developing

cancer rehabilitation programs as survival following any cancer treatment is the

primary concern of patients.

2.11 Summary

Colorectal cancer is the second most commonly diagnosed cancer in Australia and

responsible for 11% of the total cancer burden. Medical treatments usually include a

combination of surgery, RT, CT, and or targeted therapy. However the treatment of

CRC has significant consequences on patients’ pelvic floor function (bowel, bladder,

and sexual function), physical function, psychological outcomes and HRQoL.

Post-treatment pelvic floor dysfunction affects patients physically, socially and

psychologically (Fish & Temple, 2014). Impaired pelvic floor function, low

functional exercise capacity and PA levels, anxiety, and depression are prevalent in

CRC; these symptoms following CRC treatment can cause significant burden to

patient, family, and society. Supportive care interventions and symptom management

targeting patients unmet needs is critical throughout the continuum of oncology care.

The next section of the thesis focuses on measurement instruments which can be used

to assess patients’ physical and psychological function and symptoms in CRC. Such

instruments can be used to measure change in patient outcomes over time and the

efficacy of supportive care interventions such as rehabilitation programs.

Chapter 3. Outcome Measures

51


3.1 Introduction

In CRC, the disease and its treatments cause significant physical and psychological

impairments (Cheville, Beck, Petersen, Marks, & Gamble, 2009; Sweeney et al., 2006;

Yabroff, Lawrence, Clauser, Davis, & Brown, 2004). As described in the previous

chapter some of the common side effects and impairments experienced by patients

following CRC treatment are pelvic floor dysfunction, lower PA levels, muscle

strength weakness, reduced functional exercise capacity, anxiety, depression, and

impaired HRQoL (Fish & Temple, 2014; Hamaker et al., 2015; Jensen et al., 2011).

Being able to accurately measure these variables at a single point in time, as

longitudinally over time, is important to understand the impact and response to natural

history or treatments.

Measurement instruments can be performance-based instruments such as tests of

functional exercise capacity and muscle strength; clinician reported outcome

measures (CROM) such as tests of PFM (PFM) function; or patient reported outcome

measures (PROM) such as standardized, validated questionnaires (Gilbert,

Sebag-Montefiore, Davidson, & Velikova, 2015; Minneci et al., 2015; Valderas &

Alonso, 2008). To date, evidence on the validity of the measurement instruments for

pelvic floor outcomes and functional exercise capacity in patients with CRC is not

available. As the validity of an instrument or test is purpose-, setting- and

population-specific (Jerosch-Herold, 2005; Portney & Watkins, 2009; Talmage &

Rasher, 1981), it is important to assess the applicability and validity of the outcome

measures with respect to the characteristics of the CRC population.

This chapter begins by reviewing the outcome measures used in the prospective

observational studies and the non-randomized quasi-control study reported in Chapter

3, Chapter 4, Chapter 5, Chapter 6, and Chapter 7. As PROMs are standard measures

in the assessment of CRC treatment (McNair et al., 2015), these outcome measures

are discussed first. The second half of the chapter and next chapter describe Study


52

1and Study 2, which evaluated the validity of a pelvic floor symptom-specific

questionnaire and three field walking tests in CRC populations, the results of which

informed the choice of measures used in subsequent studies in this thesis.

3.2 Patient reported outcome-measures (PROM)

3.2.1 Pelvic floor symptoms

Clinical measures for PFM function, such as pad testing, urodynamic tests, anorectal

manometry, anorectal sensation and ultrasound are commonly used for classifying

pelvic floor symptom severity (Messelink et al., 2005). However, discrepancies often

exist between clinical measures of symptom severity and the subjective patient

perception of the condition (Avery et al., 2007; Chen, Emmertsen, & Laurberg, 2014).

In response to this, the measurement of pelvic floor symptoms through the use of

psychometrically robust self-completion questionnaires has become more common

and is now recognized as the gold standard of measuring the patient perspective of the

condition (Chen, Emmertsen, & Laurberg, 2015; Kelleher et al., 2013).

Avery et al. have reviewed and identified a total of 23 robust and relevant

questionnaires for the assessment of urinary and anal incontinence, and most of the

questionnaires are sex-specific (Avery et al., 2007). Among all questionnaires for

incontinence, the ICIQ-UI SF is recommended as a Grade A questionnaire to assess

combined symptoms of urinary incontinence/lower urinary tract symptoms/overactive

bladder in males and females (Avery et al., 2007).

The ICIQ-UI SF is the first module developed by the WHO-sponsored International

Consultation on Incontinence (ICI) to assess urinary incontinence and its impact on

HRQoL (Avery et al., 2004). The ICIQ-UI SF consists of three scored items related to

frequency and amount of urinary incontinence and quality of life and a self-diagnostic

item, not scored. An overall ICIQ-UI SF score is calculated as the summation of the

three scored items (Reis, Beji, & Coskun, 2010). The cut-off scores are set to ‘0’

meaning ‘no incontinence’ and ‘≥ 1’ meaning ‘urinary incontinence’ (Klovning,


53

Avery, Sandvik, & Hunskaar, 2009). The ICIQ-UI SF has been shown to have good

construct validity, acceptable convergent validity, and good reliability (Avery et al.,

2004).

Subsequently, the ICIQ-Bowel module (ICIQ-B) was developed as one of the series

questionnaires included in the ICIQ project (Abrams, Avery, Gardener, & Donovan,

2006). The ICIQ-B (Grade A+) is highly recommended by the ICI as the outcome

measures for the symptoms and impact of urinary and faecal incontinence in clinical

practice and research trials (Kelleher et al., 2013). The ICIQ-B contains a total of 21

questions; 17 of which are scored and arranged in 3 domains: bowel pattern (score

range 1-21), bowel control (score range 1-28), and quality of life (score range 0-26).

Four unscored items include other bowel symptoms and sexual impact. Higher score

indicates greater symptoms or impairment (Cotterill, Norton, Avery, Abrams, &

Donovan, 2011). Validity and reliability of ICIQ-B has been demonstrated (Cotterill,

Norton, Avery, Abrams, & Donovan, 2008; Cotterill et al., 2011). Both ICIQ-UI SF

and ICIQ-B are non-gender-specific questionnaires which have undergone extensive

psychometric testing in different patient groups, however not in CRC-specific

populations (Cotterill et al., 2011; Kelleher et al., 2013).

The APFQ is one of the few validated questionnaires that integrate bladder, bowel,

and sexual function as well as pelvic organ prolapse symptoms (Baessler, O'Neill,

Maher, & Battistutta, 2009, 2010). The APFQ was first developed as an

interviewer-administered questionnaire in Australia to assess bladder, bowel, and

sexual function; pelvic organ prolapse; and condition-specific quality-of-life issues in

community-dwelling women (Baessler, O'Neill, Maher, & Battistutta, 2008) and had

been later validated in groups of urogynaecological patients and in self-administered

format (Baessler et al., 2009). The APFQ consists of 42 questions, and the scores

within each domain were divided by the number of relevant questions and multiplied

by 10; thus, the scores range from 0-10 for each domain, giving a maximum total

score of 40 (Baessler et al., 2009). A higher score indicates more severe symptoms.

Although the APFQ was designed for females in the community (Baessler et al., 2008)

and females with pelvic floor disorders (Baessler et al., 2009), the questions in the


54

bladder and bowel function domains of the APFQ may also be applicable to males.

Baessler et al. reported that a difference of more than 3 in the total score of the APFQ

can distinguish the community and clinical populations; a difference of 0.9 in the

bowel domain score is considered clinically important (Baessler et al., 2009). The

test-retest reliability of the APFQ has also been reported (kappa coefficients 0.7 to 1.0)

(Baessler et al., 2009). Although the psychometric properties of the APFQ have been

previously established (Baessler et al., 2008, 2009, 2010), it has not been evaluated in

a sample of patients with CRC. The validation of the APFQ bladder and bowel

function domains was tested in a group of patients who have undergone surgery for

CRC later in this Chapter.

3.2.2 Pelvic floor signs

Objective bladder and bowel diaries are recommended by the ICI to be used with the

PROMs for assessment and measurement of the degree of symptoms, bother of

incontinence and impact of treatment (Staskin et al., 2013). The bladder diary is a

comprehensive instrument to document objective information such as the times of

micturition and voided volumes, leakage episodes, fluid intake, and degree of urgency

(Abrams et al., 2010). Moreover, diary patterns may characterise normal and

abnormal states (Staskin et al., 2013). A 3-day bladder diary is recommended for

accurate assessment of bladder symptoms and has been shown to be equivalent to a

7-day diary (Brown et al., 2003; Staskin et al., 2013; Wieslander, 2009).

A bowel diary is strongly recommended by the ICI (grade A) for accurate information

of faecal incontinence severity (Bliss et al., 2013). A bowel diary can be helpful in

investigating bowel symptoms (Messelink et al., 2005) and used to record bowel

movements with the time of day, time spent at toilet, presence of straining, soiling

episodes, pad usage and use of medications to assist with bowel movements (Ballard

et al., 2015), and the utilization of the Bristol Stool Form Scale is preferred to

document stool consistency (O'Donnell, Virjee, & Heaton, 1990).


55

3.2.3 Levels of physical activity

Physical activity is defined as “any bodily movement produced by skeletal muscles

resulting in energy expenditure” (Caspersen, Powell, & Christenson, 1985) and can be

measured using the validated and well-defined reference methods (e.g. double

labelled water, direct calorimetry, indirect calorimetry), objective measurements

(direct observation, pedometers, accelerometers, heart rate monitors) (Trost & O'Neil,

2014), or self-report methods (daily diaries and recall questionnaires) (Reiser &

Schlenk, 2009). Reference methods are mostly expensive and limited to the laboratory

setting (Aparicio-Ugarriza et al., 2015). Objective measurements are commonly used

in research practice but have limitations particularly due to the cost of purchasing the

device and patient burden / feasibility since the patient is required to wear the device

during waking hours for a continuous period of four to seven days (Aparicio-Ugarriza

et al., 2015). Objective measurements are understood to be more valid than self-report

(over reporting with questionnaires) (Westerterp, 2009) however self-report methods

are more practical for wider use in clinical settings (Reiser & Schlenk, 2009).

The short form version of the International Physical Activity Questionnaire (IPAQ-SF)

is commonly used to assess levels of PA in research studies and clinical practice

(Silsbury, Goldsmith, & Rushton, 2015). This is a detailed self-report questionnaire

which asks the patient about the frequency and duration of strenuous, moderate, and

mild physical activity undertaken in the previous seven days. The IPAQ-SF has good

reliability and acceptable validity (Craig et al., 2003; Lee, Macfarlane, Lam, &

Stewart, 2011; Silsbury et al., 2015). The total IPAQ-SF score in MET-minutes per

week is the summation of walking (3.3 MET), moderate activity (4.0 MET), and

vigorous (8.0 MET) activity minutes per week. Total IPAQ scores are classified as

"low" (not meeting the criteria for moderate-intensity and vigorous-intensity activity

categories), "moderate" (achieving at least 600 MET-minutes/week) and "high"

(achieving at least 3000 MET-minutes/week) (IPAQ Research Committee, 2005). The

IPAQ-SF has been used by a previous study to examine the patterns of PA in a CRC

population (Kang, 2015). Given there is no gold standard questionnaire for the

assessment of physical activity in the general or specific CRC population, we chose to


56

use the IPAQ due to its prior use in CRC, international context (to allow comparison

of data across studies) and ease of completion (Kang, 2015; Silsbury et al., 2015).

3.2.4 Anxiety and depression

There are numerous PROMs for measuring psychological morbidity in oncology

research, and Hospital Anxiety and Depression Scale (HADS) is one of the most

frequently used questionnaires to measure symptoms of anxiety, depression, and

psychological distress among patients with cancer (Yeh, Chung, Hsu, & Hsu, 2014).

The HADS includes a total of 14 items and is composed of an anxiety subscale and a

depression subscale (Zigmond & Snaith, 1983). Each subscale is scored from 0 to 21

(Zigmond & Snaith, 1983). Scores of 0–7 represent no anxiety or depression, 8–10

indicates a borderline anxiety or depression, and 11–21 indicates a clinical anxiety or

depression (Luckett et al., 2010; Zigmond & Snaith, 1983). The HADS has

demonstrated high internal consistency in patient populations including cancer

(Zigmond & Snaith, 1983) and it has also been widely used in patients with CRC

(Polat, Arpaci, Demir, Erdal, & Yalcin, 2014; Tsunoda et al., 2005). The minimal

clinically important difference (MCID) of HADS has not been established; however,

the minimal detectable change in HADS (HADS-Anxiety= 3.80; HADS-Depression=

3.99; HADS-Total= 5.68) has been reported in patients with coronary heart disease

(Wang, Chair, Thompson, & Twinn, 2009).

3.2.5 Health related quality of life (HRQoL)

European Organization for Research and Treatment of Cancer Quality of Life Core

Questionnaire (EORTC QLQ-C30) is one of the most frequently used HRQoL

instruments in CRC research (Sanoff, Goldberg, & Pignone, 2007). In this thesis,

HRQoL was evaluated using the EORTC QLQ-C30 and the CRC modules

(QLQ-CR29). The EORTC QLQ-C30 comprises 30 items assessing functional and

symptom aspects of HRQoL; the QLQ-CR29 consists of 18 items assessing

gastrointestinal symptoms, pain and problems with micturition, and separate scales for

the patients with or without a stoma and for men and women’s sexual function


57

(Whistance et al., 2009). The QLQ-CR29 was implemented in conjunction with the

EORTC QLQ-C30, giving a total of 59 items. All EORTC scale/single item measures

range in score from 0-100. A higher score on the functional and the global HRQoL

scale represents a high level of functioning and high HRQoL, while a higher score on

the symptom scale represents a high level of symptomatology. Osoba et al. has shown

that a mean change of 5 to 10 points on the EORTC QLQ-C30 indicates a “little”

change; a change of 10 to 20 points indicates a “moderate” change; and a change of

greater than 20 points indicates a “large” change (Osoba, Rodrigues, Myles, Zee, &

Pater, 1998). The EORTC QLQ-C30 and QLQ-CR29 have been shown to valid and

reliable to assess HRQoL in clinical trials and research in patients with CRC (Ganesh

et al., 2016; Whistance et al., 2009).

3.2.6 Self efficacy

Self-efficacy determines whether an individual’s coping behaviour will be initiated,

how much effort will be expended, and how long it will be sustained in face of

obstacles and adverse experiences (Bandura, 1977). As efficacy beliefs are

task-specific, different self-efficacy measures are required to assess the outcomes of

interest (Lev, 1997). The Physical Exercise Self-Efficacy Scale (PES) and Nutrition

Self-Efficacy Scale (NES) of the Health-Specific Self-Efficacy Scale developed by

Schwarzer and Renner (Schwarzer & Renner, 2005) were used in the study presented

in Chapter 6 to assess changes in self-efficacy before and after an oncology

rehabilitation program which implemented an international guideline on nutrition and

PA for cancer survivors (Rock et al., 2012). The PES and NES each consists of five

items, which are scored on a 4-point Likert-type scale (1 = very uncertain, 2 = rather

uncertain, 3 = rather certain, and 4 = very certain) (Schwarzer & Renner, 2005). The

total score of each scale is the sum of the responses to the 5 items ranging from 5-20.

Higher score indicates higher self-efficacy. The Health-Specific Self Efficacy Scale

has been shown to have satisfactory psychometric properties, with a Cronbach’s alpha

of 0.87 for NES and 0.88 for PES (Schwarzer & Renner, 2005). The Health-Specific

Self-Efficacy Scale has been widely used in patients with chronic diseases (Clarke,

2009).


58

3.3 Clinical-reported outcome measures / performance-based outcome measures

3.3.1 Pelvic floor muscle function

Pelvic floor muscle function can be measured using manual or digital muscle testing,

pressure manometry, and ultrasound (Bø & Sherburn, 2005; Messelink et al., 2005).

Digital rectal examination is a common basic examination performed by the

gastroenterologist in patients with CRC and by the physiotherapist in patients with

bowel dysfunction (Bols et al., 2007; Lindsetmo, Joh, & Delaney, 2008). The DRE is

performed with the patient in the left lateral position by inserting a lubricated, gloved

index finger into the rectum to determine resting and squeeze pressure (Talley, 2008).

Worldwide, several scales of digital muscle testing are in use for PFM strength testing.

In this thesis, the International Continence Society (ICS) scale, which has been

recommended by the ICS, was chosen to grade the PFM contraction. Resting pressure

is scored as “increased”, “normal” or “reduced” at the discretion of the investigator

(Dobben et al., 2007). Squeeze pressure or maximum voluntary contraction (MVC) is

scored as “absent”, “weak”, “moderate” or “strong” (Haylen et al., 2010; Messelink et

al., 2005). The reliability of DRE for the evaluation of anal sphincter tone is

conflicting. Some studies have shown poor correlations between manometric findings

and digital assessment (Eckardt & Kanzler, 1993), while some showed significant

correlations between digital and manometric assessment of resting and squeeze anal

sphincter function (Hallan, Marzouk, Waldron, Womack, & Williams, 1989).

An anorectal manometer is a reliable instrument in the assessment of anorectal

pressure and is widely used in patients with incontinence (Kerschan-Schindl et al.,

2002; Messelink et al., 2005; Probst et al., 2010). The Peritron was used as the

anorectal manometry in this thesis as it is inexpensive and simple to operate, has been

used mainly in the setting of outpatient manometry (Simpson, Kennedy, Nguyen,

Dinning, & Lubowski, 2006), and has satisfactory correlations with standard

manometry equipment (Simpson et al., 2006). The Peritron manometer


59

(Cardio-Design, Australia) consists of an anal probe connecting to an electronic

device that shows the values of contraction in centimetre of water (cmH2O) (Cardio

Design, 2016). Anorectal manometry is tested in the same position as for DRE (i.e.

left lateral position). The anal resting and squeeze pressures are assessed by inserting

the anal probe of the Peritron in the anus. A single pressure recording (displayed

numerically in cm H2O) reflects the average pressure generated in the anal canal

(Simpson et al., 2006). The Peritron has been shown to be to be highly reliable in

measuring PFM strength and endurance (Hundley, Wu, & Visco, 2005; Rahmani &

Mohseni-Bandpei, 2011).

Transperineal ultrasound (TPUS) is useful in the clinical assessment of PFM function

(Thompson, O'Sullivan, Briffa, Neumann, & Court, 2005) and is increasingly used for

anorectal evaluation (Albuquerque & Pereira, 2016). The TPUS used in this thesis is a

GE Voluson-e System (GE Medical System) with a 4D transducer RAB4-8RS

(4-8MHz). The participant is tested in supine position with hips and knees flexed to

60 degrees. The ultrasound transducer is placed in the mid-sagittal plane at the

perineum (Dietz, 2010). A 2-dimensional image of the pelvic floor is visualized with

a field of view of 70 degrees in the sagittal plane. Anorectal angle (in degrees)

(Raizada et al., 2010), levator hiatus anterior-posterior (A-P) distance (in centimetres)

(Oversand, Kamisan Atan, Shek, & Dietz, 2015), and distance from anorectal angle to

the horizontal reference line (in centimetres) are measured at rest and at MVC (best of

three contractions) (van Delft, Thakar, & Sultan, 2015). The anorectal angle is formed

by the longitudinal axis of the anal canal and the posterior rectal wall (Raizada et al.,

2010). The levator hiatus A-P distance (in centimetres) is measured from the lower

edge of the pubic symphysis to the anorectal angle (Oversand et al., 2015). The

distance from anorectal angle to the horizontal reference line is measured from the

anorectal angle to a horizontal line drawn from pubic symphysis parallel to the

transducer surface (Raizada et al., 2010). Previous studies have found significant

correlations between the assessment of PFM strength by digital palpation and

objective 2D and 3D ultrasound parameters in urogynaecological patients (Albrich et

al., 2015) and healthy women (Volloyhaug, Morkved, Salvesen, & Salvesen, 2015).


60

Transperineal ultrasound has also been shown to be reliable to measure the PFM

function in male and female populations (Roll et al., 2015; Thompson et al., 2005).

3.3.2 Functional exercise capacity

Physical function is a measure of functional exercise capacity. There is no common

definition of physical function. According to the Patient-Reported Outcomes

Measurement Information System, physical function is defined as “the ability to carry

out various activities that require physical capability, ranging from self-care to

more-vigorous activities that require increasing degrees of mobility, strength, or

endurance" (Bruce et al., 2009). Physical function can be measured in many ways.

One of the most fundamental measures is functional exercise capacity (Evans, 2002).

Functional exercise capacity is the maximal performance in a given domain (Larson,

2007) and can be measured directly by determining the VO2peak or estimated from the

highest treadmill or cycle work rate achieved (Fleg et al., 2000). The VO2peak is the

one of the gold standard in the assessment of exercise tolerance (Vanhees et al., 2005)

and can be measured by the CPET with continuous gas exchange analysis during

incremental exercise (Steins Bisschop et al., 2012). However, laboratory-based testing

(i.e. CPET) usually requires an experienced technician and is complex, time

consuming and expensive (Jones, Eves, Haykowsky, Joy, & Douglas, 2008). Details

of the CPET procedure are described in Chapter 4. The 6MWT (Holland et al., 2014),

ISWT (Singh, Morgan, Scott, Walters, & Hardman, 1992), and ESWT (Revill,

Morgan, Singh, Williams, & Hardman, 1999) are commonly performed field walking

tests in clinical settings for functional exercise capacity as these tests are easy to

perform, time efficient, and require only portable equipment.

The 6MWT is a self-paced field walking test. Participants are asked to walk as far as

possible over a 30-meter course in 6 minutes as per published guidelines (American

Thoracic Society) (ATS Committee on Proficiency Standards for Clinical Pulmonary

Function Laboratories, 2002). The total distance walked in meters is documented.

Participant’s heart rate, oxygen saturation (SpO2), and perceived exertion and leg


61

fatigue are recorded before and after the test (Kendrick, Baxi, & Smith, 2000). The

6MWT is recommended to be performed on two occasions to account for a learning

effect and the best test result is used in analysis (Spencer, Alison, & McKeough, 2008;

Wu, Sanderson, & Bittner, 2003). In patients with cancer, the 6WMT is reliable (the

intraclass correlation coefficient [ICC] r = 0.93) and valid (CPET VO2peak r = 0.67)

(Schmidt et al., 2013). The 6MWT is well validated for patients with cardiac or

pulmonary disease (Fotheringham et al., 2015; Guazzi, Dickstein, Vicenzi, & Arena,

2009; Singh et al., 2014), and has been reported as a valid measure for patients post

colorectal surgery (Moriello, Mayo, Feldman, & Carli, 2008). The MCID has not

been reported specifically for patients with CRC, however in patients with coronary

artery disease who have undergone a cardiac rehabilitation program it is 25 meters

(Gremeaux et al., 2011), in patients with lung cancer (many following surgery) it is 22

meters to 42 meters (Granger, Holland, Gordon, & Denehy, 2015), and in patients

with respiratory disease it is 25 meters to 33 meters (Holland et al., 2014).

The ISWT is an externally-paced incremental field walking test (Singh et al., 1992).

The distance in meters that an individual can walk up and down a 10-meter course

paced according to an incremental walking speed dictated by an audio signal is

measured. The speed increases every minute, and the test finishes when the

participant is unable to maintain the required speed or limited by dyspnoea or a heart

rate >85% predicted maximum (Singh et al., 1992). Duplicate tests are completed to

account for the learning effect, and the best test result is used in analysis (McKeough,

Leung, & Alison, 2011; Singh et al., 2014). The MCID in the ISWT for patients

following cardiac rehabilitation is 70 meters (Houchen-Wolloff, Boyce, & Singh,

2015). The ISWT has been shown to have good reliability (ICC > 0.75) and strong

correlations with the VO2peak (r ≥ 0.70) in patients with various diseases, such as

COPD, chronic heart failure, cardiomyopathy, and cystic fibrosis, and in patients who

have undergone cardiovascular, abdominal, or lung cancer surgery (Parreira et al.,

2014). The ISWT has also been shown to be valid and reliable to assess maximal

exercise capacity in patients with advanced cancer (Booth & Adams, 2001; Parreira et

al., 2014).


62

The ESWT is an externally-paced field walking test of endurance capacity. It is

performed along the same course as the ISWT according to published guidelines

(Revill et al., 1999). The walking speed is pre-set at the pace equivalent to 85% of the

VO2peak calculated from the ISWT (Hill et al., 2012b). Patients are instructed to walk

for as long as possible until they are unable to maintain the required speed or became

breathless, and the endurance time in seconds is recorded. A single ESWT is

performed as no learning effect is reported for ESWT (McKeough et al., 2011; Ngai,

Spencer, Jones, & Alison, 2015). The ESWT has been shown to be valid in patients

with COPD (Revill et al., 1999) and very responsive to bronchodilation (Borel, Pepin,

Mahler, Nadreau, & Maltais, 2014) and pulmonary rehabilitation (Altenburg, de Greef,

ten Hacken, & Wempe, 2012; Eaton, Young, Nicol, & Kolbe, 2006).

3.3.3 Muscle strength

Hand held dynamometry for manual muscle testing is a common, simple

measurement of strength and has been used in many patient populations including

cancer. Hand-grip strength as an indicator of general muscle strength is measured

using the Jamar dynamometer (Lafayette Instrument Company, USA). The participant

is tested in the position recommended by the American Society for Hand Therapists

(Peolsson, Hedlund, & Oberg, 2001). Three measurements are made from both hands

of each participant and only the maximum values obtained from each hand are used

(Vaz, Thangam, Prabhu, & Shetty, 1996). Grip strength has been shown to be a

predictor of postoperative complications, mortality, and functional decline (Bohannon,

2001) and a strong predictor of all-cause death, cardiovascular death, and

cardiovascular disease (Leong et al., 2015). Hand-held dynamometry has been shown

to be a reliable, objective instrument for hand-grip strength (Mathiowetz, 2002;

Roberts et al., 2011). The MCID in grip strength is 5.0 kg and 6.2 kg for the affected

dominant and non-dominant sides in stroke respectively (Lang, Edwards, Birkenmeier,

& Dromerick, 2008) and 6.5 kg in patients treated for distal radius fracture (Kim, Park,

& Shin, 2014).


63

3.4 Summary of outcome measures chosen for the studies in this thesis

The first part of this chapter has summarised the outcome measures included in the

studies described in the second part of Chapter 3, Chapter 4, Chapter 5, Chapter 6,

and Chapter 7. The outcome measures are chosen from the previous CRC and pelvic

floor research studies to measure the wide range of dysfunction and symptoms which

are likely to present after surgery and respond to an intervention. There is a paucity of

literature available to guide selection of the outcome measures that would be valid

and applicable in the population undergoing CRC surgery or an oncology

rehabilitation following CRC surgery. Hence the validity and applicability of some

commonly used CROMs and PROMs were investigated and reported in the next

section of this chapter, as well as Chapter 4 and Chapter 7.

3.5 Validation study of the Australian Pelvic Floor Questionnaire in patients

following surgery for colorectal cancer

This study is currently in press:

Lin K-Y, Frawley H.C., Granger C.L., Denehy L. (2016). The APFQ is a valid

measure of pelvic floor symptoms in patients following surgery for colorectal cancer.

Neurourology and Urodynamics. Accepted (24/08/2016).

Author contributions for this chapter are the following: K-YL, HF, CG and LD

conceived the idea for the paper. K-YL, HF, CG and LD contributed to research

design. K-YL, HF and CG contributed to data acquisition. K-YL, HF, CG and LD

contributed to data analysis and interpretation. K-YL completed all statistical analyses.

K-YL wrote the first draft of the manuscript and managed manuscript submission. All

authors revised the paper and provided scientific input. All authors approved the final

version of the manuscript.


64

3.5.1 Introduction

This chapter will describe an analysis of data from two prospective studies to assess

the construct validity (Frost et al., 2007), and clinical utility (Mullins-Sweatt, Lengel,

& DeShong, 2016) of the bladder and bowel function domains of the APFQ compared

with two existing bladder and bowel questionnaires (i.e. ICIQ-UI SF and ICIQ-B) in

patients following surgery for CRC. Many symptom-specific or HRQoL

questionnaires (i.e. LAR Syndrome Score and EORTC QLQ-CR29) have been

developed and used to measure bladder and/or bowel dysfunction in patients with

CRC (Emmertsen & Laurberg, 2012; Whistance et al., 2009), however these measures

are either designed specifically for use in patients with rectal cancer or are lengthy

and time-consuming to complete. The APFQ is one of the few validated

questionnaires that integrates bladder, bowel, and sexual function as well as pelvic

organ prolapse symptoms (Baessler et al., 2009, 2010). Although the psychometric

properties of the APFQ have been previously established (Baessler et al., 2008, 2009,

2010), it has not been evaluated in a sample of patients with CRC. We hypothesized

that the bladder and bowel domains of the APFQ, which are less lengthy and more

symptom specific than the corresponding questions in the LAR Syndrome Score and

the EORTC QLQ-CR29, are also valid and applicable to patients with CRC.

This chapter contains content that is substantially unchanged from the content of the

paper which has been accepted for publication.

3.5.1.1 Study aims

Aim 1: To assess the construct validity, and clinical utility of the bladder and bowel

function domains of the APFQ compared with two existing bladder and bowel

questionnaires (i.e. ICIQ-UI SF and ICIQ-B) in patients following surgery for CRC.

Aim 2: To determine the predictors of post-operative bladder and bowel symptoms in

patients undergoing surgery for CRC


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3.5.2 Materials and Methods

Study design

This was an analysis of data from two ongoing prospective clinical studies at three

large hospitals in Melbourne Australia, two private and one public.

Study 1 is a prospective observational study to assess pelvic floor symptoms,

anorectal muscle function, functional outcomes, emotional distress, and HRQoL in

patients who undergo surgery for CRC. The study was approved by the Melbourne

Health Human Research Ethics Committee (HREC).

Study 2 is a prospective observational pre-post study to investigate the feasibility of a

general oncology rehabilitation program for patients following surgery for

abdomino-pelvic cancer (Australian New Zealand Clinical Trials Registry [ANZCTR]:

12614000580673). The study had ethics approval from Cabrini Hospital HREC.

Participants

Participants included patients who had undergone surgery for histologically

confirmed stage I-III CRC; had an Eastern Cooperative Oncology Group performance

status of between 0-2 (0 = fully active, 2 = up and about for 50% of a day); and had

sufficient English language skills to participate. Patients were excluded if they were

aged 86 and over, were pregnant or up to 12 months postpartum, or had severe

physical/psychiatric impairments. Data from all participants who were eligible from

the two ongoing prospective clinical studies and recruited between October 2013 and

August 2015 were used for analysis. Written informed consent was obtained from all

participants before completing the measurements.

Measures

Bladder and bowel symptoms were assessed using the bladder and bowel function

domains of the APFQ, ICIQ-UI SF, and ICIQ-B at six to eight weeks post-cancer

treatment.


66

The APFQ is an instrument consisting of 42 questions in 4 domains (bladder, bowel,

and sexual function and pelvic organ prolapse) (Baessler et al., 2009). The scores

within each domain are divided by the number of relevant questions and multiplied by

10; thus, the scores range from 0 to 10 for each domain, giving a maximum total score

of 40 (Baessler et al., 2009). We chose to focus on the bladder and bowel function

domains, which contain 15 and 12 questions respectively, and the maximum total

score for both bladder and bowel function domains combined is 20. A higher score

indicates more severe symptoms. The APFQ has been validated in groups of

urogynaecological patients (Baessler et al., 2009) and applied in broad populations

(Laterza, Schrutka, Umek, Albrich, & Koelbl, 2015; Yang, Lim, Rah, & Kim, 2012).

The ICIQ-UI SF was developed to evaluate the severity of urinary incontinence and

its impact on HRQoL. It consists of three scored items related to frequency and

amount of urinary incontinence and quality of life and a self-diagnostic item, not

scored. An overall ICIQ-UI SF score is calculated as the summation of the three

scored items and ranges from 0 to 21. Urinary incontinence is defined as either absent

(score 0) or present (score ≥ 1) on the ICIQ-UI SF (Avery et al., 2004). Higher score

indicates worse symptom severity or greater impact of symptoms on HRQoL. The

ICIQ-UI SF has been shown to have good psychometric properties in patients with

incontinence or other lower urinary tract symptoms and is suitable for use in clinical

practice and research (Avery et al., 2004).

The ICIQ-B is a non-gender-specific questionnaire developed to evaluate anal

incontinence symptoms and impact on quality of life and contains a total of 21

questions. Seventeen of 21 questions are scored and arranged in three domains: bowel

pattern (score range 1-21), bowel control (score range 0-28), and quality of life (score

range 0-26). Four unscored items include other bowel symptoms and sexual impact. A

five-point Likert scale is used for most questions to assess the presence or absence of

a symptom and its severity, followed by visual analogue scale of 0–10 to assess

associated bother (Cotterill et al., 2011). Higher scores indicate greater impairment or

symptoms (Cotterill et al., 2011). The ICIQ-B has been shown to be a


67

psychometrically robust instrument for use in patients with anal incontinence of

varying causes (Cotterill et al., 2011).

Statistical analysis

Statistical analysis was performed using SPSS Windows Version 22.0 (SPSS,

Chicago, IL, USA). Demographic and clinical outcome data of the participants were

analysed using descriptive statistics, such as mean and standard deviation (SD),

median and interquartile range (IQR), or number and percentage. The differences in

the participants’ characteristics between male and females were compared using the

independent t-test or Mann-Whitney U test for continuous variables, and χ2 test for

categorical variables. Pearson's correlation coefficients were used to examine the

bivariate relationships among the bladder domain of the APFQ and the total score of

ICIQ- UI SF, as well as the correlations between the bowel domain of the APFQ and

ICIQ-B subscales. The strength of the correlation was determined by the correlation

coefficient values (0.00–0.30 = negligible; 0.30–0.50 = low positive correlation; 0.50–

0.70 = moderate positive correlation; 0.70–0.90 = high positive correlation; and 0.90–

1.00 = very high positive correlation) (Zou, Tuncali, & Silverman, 2003).

The score of each instrument was categorized as symptomatic or asymptomatic using

a cut-off score of greater than or equal to 1, based on the cut-off value reported in

previous studies (Avery et al., 2004; Baessler et al., 2009). Kappa coefficients were

calculated to determine the agreement between questionnaires. A kappa value of less

than 0.40 was considered poor-to-fair agreement, 0.41-0.60 moderate agreement,

0.61-0.80 substantial agreement, and 0.81-1.00 almost perfect agreement (Landis &

Koch, 1977).

A Logistic regression model was applied to calculate the ORs to estimate whether

variables (age, level of tumour, and stage of cancer) identified by univariate analysis

(p-value < 0.20) (Table 3-1and Table 3-2) could predict the occurrence of

dichotomised bladder or bowel symptoms following CRC surgery. As this study was

an exploratory analysis, no power calculation was carried out. P values < 0.05 were

considered statistically significant.


68

3.5.3 Results

Participant characteristics

Data from 44 participants (25 males and 19 females) with a mean age of 64.8 years

(SD = 14.1, range 26-85 years) were collected from the two studies (Figure 3.1).

Eighty-two percent and 18% had a confirmed diagnosis of colon cancer and rectal

cancer respectively. Seventy-five percent had not undergone any adjuvant therapies at

the time of diagnosis. Thirty-six percent had bladder symptoms and 66% had bowel

symptoms as assessed using the APFQ bladder and bowel domains; conversely, 64%

did not have bladder symptoms and 34% did not have bowel symptoms six to eight

weeks following cancer treatment (Table 3-3). No statistically significant differences

were found in socio-demographic and clinical characteristics and the number of

participants being symptomatic (APFQ bladder and APFQ bowel ≥ 1) between male

and females. Table 3-4 shows the descriptive statistics for APFQ bladder and bowel

domains, total score of ICIQ-UI SF, and ICIQ-B subscales as well as the number of

participants with a score above the cut-off score of being symptomatic. No

statistically significant differences existed in the number of participants being

symptomatic as assessed using the APFQ, ICIQ-UI SF, and ICIQ-B between males

and females (Table 3-4). Age (p = 0.002) was significantly different between

participants with or without bladder symptoms (Table 3-1). However, no significant

differences were found in demographic and clinical variables between groups with or

without bowel symptoms (Table 3-2).


69

Table 3-1: Demographic and clinical variables in participants with and without bladder symptoms following surgery for colorectal cancer

Variables Total Males Females

Symptomatic

APFQ

bladder Score

≥ 1

Asymptomatic

APFQ bladder

Score < 1

p-value Symptomatic

APFQ

bladder Score

≥ 1

Asymptomatic

APFQ bladder

Score < 1

p-value Symptomatic

APFQ

bladder Score

≥ 1

Asymptomatic

APFQ bladder

Score < 1

p-value

Age, years

(mean±SD)a

73.3 ± 8.6 59.7 ± 15.1 0.002 71.6 ± 9.2 59.1 ± 14.4 0.023 76.0 ± 7.4 61.2±15.0 0.036

Genderb 0.565 - -

Male 10 (62.5) 15 (53.6) - - - - - -

Female 6 (37.5) 13 (46.4) - - - - - -

Level of

tumour, n

(%)b

0.941 1.00 0.943

Colon 13 (81.3) 23 (82.1) 8 (80.0) 12 (80.0) 5 (83.3) 11 (84.6)

Rectum 3 (18.8) 5 (17.9) 2 (20.0) 3 (20.0) 1 (16.7) 2 (15.4)

Adjuvant

treatment, n

(%)b

1.000 0.610 0.554

Yes 4 (25.0) 7 (25.0) 3 (30.0) 6 (40.0) 1 (16.7) 1 (7.7)

No 12 (75.0) 21 (75.0) 7 (70.0) 9 (60.0) 5 (83.3) 12 (92.3)

Length of

stay, days

(median,

IQR)c

8 (5.3 - 10.8) 7 (6.0 - 12.5) 0.802 8 (5.8 - 10.3) 8 (6.0 - 15.0) 0.696 6 (4.5 - 17.8) 6 (4.8 - 12.3) 1.000

Type of

surgery, n

(%)b

0.820 0.622 0.419


70

Resection of

colon

8 (50) 15 (53.6) 5 (50.0) 6 (40.0) 3 (50.0) 9 (69.2)

Resection of

rectum

8 (50) 13 (46.4) 5 (50.0) 9 (60.0) 3 (50.0) 4 (30.8)

Stage of

cancer, n

(%)b

0.397 0.106 0.765

I 7 (43.8) 8 (28.6) 5 (50.0) 2 (13.3) 2 (33.3) 6 (46.2)

II 6 (37.5) 8 (28.6) 3 (30.0) 4 (26.7) 3 (50.0) 4 (30.8)

II 3 (18.8) 10 (35.7) 2 (20.0) 8 (53.3) 1 (16.7) 2 (15.4)

Missing 0 (0) 2 (7.1) 0 (0) 1 (6.7) 0 (0) 1 (7.7) Abbreviations: APFQ, Australian Pelvic Floor Questionnaire; IQR, interquartile range; SD, standard deviation.

a Independent t test

b Chi-Square test

c Mann-Whitney U test


71

Table 3-2: Demographic and clinical variables in participants with and without bowel symptoms following surgery for colorectal cancer


Symptomati

c APFQ

bowel Score

≥ 1

Asymptomati

c

APFQ bowel

Score < 1

p-valu

e

Symptomati

c APFQ

bowel Score

≥ 1

Asymptomati

c

APFQ bowel

Score < 1

p-valu

e

Symptomati

c APFQ

bowel Score

≥ 1

Asymptomati

c

APFQ bowel

Score < 1

p-valu

e

Age, years

(mean±SD)a

67.3 ± 12.3 61.1 ± 17.4 0.204 66.2 ± 13.8 59.6 ± 13.8 0.278 67.7 ± 7.0 62.7 ± 21.9 0.494

Genderb 0.737 - -

Male 17 (58.6) 8 (53.3) - - - - - -

Female 12 (41.4) 7 (46.7) - - - - - -

Level of

tumour, n

(%)b

0.294 0.668 0.243

Colon 25 (86.2) 11 (73.3) 14 (82.4) 6 (75.0) 11 (91.7) 5 (71.4)

Rectum 4 (13.8) 4 (26.7) 3 (17.6) 2 (25.0) 1 (8.3) 2 (28.6)

Adjuvant

treatment, n

(%)b

0.582 0.915 0.253

Yes 8 (27.6) 3 (20) 6 (35.3) 3 (37.5) 2 (16.7) 0 (0)

No 21 (72.4) 12 (80) 11 (64.7) 5 (62.5) 10 (83.3) 7 (100)

Length of

stay, days

(median,

IQR)c

7 (6 - 11.3) 8 (5 - 13) 0.841 8 (6 - 11) 8.5 (6.5 -

13.5)

0.711 6 (5.5 - 13.5) 6 (4.0 - 13.0) 0.606

Type of

surgery, n

(%)b

0.592 0.653 0.678

Resection

of colon

16 (55.2) 7 (46.7) 8 (47.1) 3 (37.5) 8 (66.7) 4 (57.1)


72

Resection

of rectum

13 (44.8) 8 (53.3) 9 (52.9) 5 (62.5) 4 (33.3) 3 (42.9)

Stage of

cancer, n

(%)b

0.964 0.499 0.681

I 10 (34.5) 5 (33.3) 6 (35.3) 1 (12.5) 4 (33.3) 4 (57.1)

II 9 (31.0) 5 (33.3) 4 (23.5) 3 (37.5) 5 (41.7) 2 (28.6)

II 9 (31.0) 4 (26.7) 7 (41.2) 3 (37.5) 2 (16.7) 1 (14.3)

Missing 1 (3.4) 1 (6.7) 0 (0) 1 (12.5) 1 (8.3) 0 (0) Abbreviations: APFQ, Australian Pelvic Floor Questionnaire; IQR, interquartile range; SD, standard deviation.

a Independent t test

b Chi-Square test

c Mann-Whitney U test


73

Figure 3.1: Flow chart of the two studies

Study 1

Six weeks post-op assessment

(T2) (n = 17/20)

Six months post-op assessment (T3)

Data available for analysis: n = 44 Study 1: n = 17

Study 2: n = 27

Eligible (n = 20)

Lost to follow-up (n = 3)

o Unable to

contact n = 3

Study 2

Eligible (n = 27)

Consented to

“questionnaire” (n =

13)

Consented to

“rehabilitation” (n =

14)

8-week general oncology

rehabilitation program

Complete assessment/questionnairs post-intervention or at 2 months after

baseline assessment (T2)

Baseline assessment (T1) (six weeks post-op)

“Questionnaire” group (n = 13)

“Rehabilitation” group (n = 14)

Pre-operative assessment (T1) (n = 20)


74

Table 3-3: Characteristics of participants

Variables Total (n =

44)

Males (n = 25,

56.8%)

Females (n = 19,

43.2%)

Age, years (mean ± SD) 64.8 ± 14.1

(range 26 -

85)

64.1 ± 13.8 (range

30 - 84)

65.8 ± 14.7 (range 26

- 85)

Level of tumour, n (%)

Colon 36 (81.8) 20 (80) 16 (84.2)

Rectum 8 (18.2) 5 (20) 3 (15.8)

Adjuvant treatment, n

(%)

Preoperative

chemoradiotherapy

2 (4.5) 2 (8) 0 (0)

Postoperative

chemotherapy

8 (18.2) 7 (28) 1 (5.3)

Preoperative

chemoradiotherapy +

postoperative

chemotherapy

1 (2.3) 0 (0) 1 (5.3)

No adjuvant therapies 33 (75.0) 16 (64) 17 (89.5)

Length of stay, days

(median, IQR)

7.0 (6.0 -

11.5)

8.0 (6.0 - 11.0) 6.0 (5.0 - 12.8)

Type of surgery, n (%)

Right hemicolectomy 16 (36.4) 7 (28) 9 (47.4)

Left hemicolectomy 2 (4.5) 2 (8) 0 (0)

Subtotal or total

colectomy

5 (11.4) 2 (8) 3 (15.8)

Abdominoperineal

resection/excision

1 (2.3) 1 (4) 0 (0)

High anterior resection 10 (22.7) 8 (32) 2 (10.5)

Ultra-low anterior

resection

10 (22.7) 5 (20) 5 (26.3)

Stage of cancer, n (%)

I 15 (34.1

)

7 (28) 8 (42.1)

IIA 11 (25.0) 7 (28) 4 (21.1)

IIB 2 (4.5) 2 (10.5)

IIC 1 (2.3) 1 (5.3)

IIIA 7 (15.9) 7 (28)

IIIB 4 (9.1) 2 (8) 2 (10.5)

IIIC 2 (4.5) 1 (4) 1 (5.3)

Missing 2 (4.5) 1 (4) 1 (5.3)

Symptomatic, n (%)

Bladder (APFQ bladder

≥ 1)

16 (36.4) 10 (40.0) 6 (31.6)

Bowel (APFQ bowel ≥

1)

29 (65.9) 17 (68.0) 12 (63.2)

Abbreviation: IQR, interquartile range; SD, standard deviation; APFQ, Australian Pelvic Floor

Questionnaire.


75

Table 3-4: Severity of bladder and bowel symptoms

Variables Total (n = 44) Males (n = 25) Females (n = 19)

Median

(IQR)

Score ≥

1, n (%)

Median

(IQR)

Score ≥

1, n (%)

Median

(IQR)

Score ≥

1, n (%)

Bladder

symptoms

APFQ

bladder

0.56 (0.22

- 1.33)

16 (36.4) 0.67 (0.22

– 1.33)

10 (40) 0.44 (0.22

- 1.33)

6 (31.6)

ICIQ-UI

SF Total

(total n=31;

males

n=17;

females

n=14)

0.00 (0.00

- 1.00)

8 (25.8) 0.00 (0.00

- 0.00)

3 (17.6) 0.00 (0.00

- 1.50)

5 (35.7)

Bowel

symptoms

APFQ

bowel

1.47 (0.59

- 2.28)

29 (65.9) 1.47 (0.44

- 2.65)

17 (68) 1.47 (0.59

- 1.77)

12 (63.2)

ICIQ-B

Bowel

pattern

5.50 (4.00

- 7.00)

39 (88.6) 6.00 (4.50

- 9.50)

22 (88) 4.00 (3.00

- 7.00)

17 (89.5)

ICIQ-B

Bowel

control

1.00 (0.00

- 5.50)

27 (61.4) 2.00 (0.00

- 6.50)

16 (64) 1.00 (0.00

- 3.00)

11 (57.9)

ICIQ-B

Quality of

life

1.00 (0.00

- 4.00)

27 (61.4) 1.00 (0.00

- 6.00)

16 (64) 1.00 (0.00

- 4.00)

11 (57.9)

Abbreviations: APFQ, Australian Pelvic Floor Questionnaire; ICIQ-B, International Consultation on

Incontinence Questionnaire-Bowel Module; ICIQ-UI SF, International Consultation on Incontinence

Questionnaire Short Form Questionnaire for urinary incontinence; IQR, interquartile range.

Correlations

The correlation coefficients between the APFQ and ICIQ-UI SF or ICIQ-B in this

cohort / study are given in Table 3-5 (total cohort), Table 3-6 (males) and Table 3-7

(females). In the total cohort, moderate correlations were observed between the APFQ

bladder domain and the ICIQ-UI SF total score (r = 0.74), and the APFQ bowel

domain and all ICIQ-B subscales (range r = 0.69-0.78), which support good

convergent validity of APFQ in patients following CRC surgery (Table 3-5). Gender

subgroup analyses yielded similar results. In males, the APFQ bladder domain was

significantly and moderately correlated with the total ICIQ-UI SF score (r = 0.71) and

APFQ bowel domain with all ICIQ-B subscales (range r = 0.69-0.79) (Table 3-6). In


76

females, the APFQ bladder domain and ICIQ-UI SF showed a significant and high

positive correlation (Table 3-7). Nonetheless, APFQ bladder domain was also

moderately correlated with ICIQ-B bowel control (r = 0.80) and weakly correlated

with ICIQ-B quality of life (r = 0.51). The APFQ bowel domain showed moderate

correlations with ICIQ-B subscales - bowel pattern, bowel control, and quality of life

in females (Table 3-7). The three ICIQ-B subscales significantly correlated with each

other in the total cohort and both sexes.

Table 3-5: Correlations between AFPQ bladder and bowel domains, ICIQ-UI SF and

ICIQ-B in total cohort (n=44)

APFQ

Bladder

ICIQ-UI

SF Total

APFQ

Bowel

ICIQ-B

Bowel

pattern

ICIQ-B

Bowel control

ICIQ-B Quality

of life

APFQ

Bladder - 0.74** 0.35* 0.14 0.45** 0.23

ICIQ-UI SF

Total 0.74** - 0.29 0.05 0.39* 0.20

APFQ Bowel 0.35* 0.29 - 0.78** 0.69** 0.77**

ICIQ-B

Bowel pattern 0.14 0.05 0.78** - 0.62** 0.78**

ICIQ-B

Bowel control 0.45** 0.39* 0.69** 0.62** - 0.67**

ICIQ-B

Quality of life 0.23

0.20 0.77** 0.78** 0.67** -



Questionnaire Short Form Questionnaire for urinary incontinence.

**p < 0.01 level (2-tailed)

*p < 0.05 level (2-tailed)

N = 44 for all correlations except the ICIQ-UI SF total (N = 31).


77

Table 3-6: Correlations between AFPQ bladder and bowel domains, ICIQ-UI SF, and

ICIQ-B in males (n = 25)

APFQ

Bladder

ICIQ-UI

SF Total

APFQ

Bowel

ICIQ-B

Bowel

pattern

ICIQ-B

Bowel

control

ICIQ-B

Quality of

life

APFQ Bladder - 0.71** 0.40 0.11 0.16 0.04

ICIQ-UI SF

Total 0.71** - 0.42 0.09 0.11 0.14

APFQ Bowel 0.40 0.42 - 0.79** 0.69** 0.78**

ICIQ-B Bowel

pattern 0.11 0.09 0.79** - 0.74** 0.76**

ICIQ-B Bowel

control 0.16 0.11 0.69** 0.74** - 0.62**

ICIQ-B Quality

of life 0.04 0.14 0.78** 0.76** 0.62** -




** p < 0.01 level (2-tailed)


Table 3-7: Correlations between AFPQ bladder and bowel domains, ICIQ-B, and

ICIQ-UI SF in females (n = 19)

APFQ

Bladder

ICIQ-UI

SF Total

APFQ

Bowel

ICIQ-B

Bowel

pattern

ICIQ-B

Bowel

control

ICIQ-B

Quality of

life

APFQ Bladder - 0.83** 0.30 0.19 0.80** 0.51*

ICIQ-UI SF

Total

0.83** - 0.23 0.05 0.80** 0.36

APFQ Bowel 0.30 0.23 - 0.75** 0.70** 0.77**

ICIQ-B Bowel

pattern

0.19 0.05 0.75** - 0.47* 0.82**

ICIQ-B Bowel

control

0.80** 0.80** 0.70** 0.47* - 0.75**

ICIQ-B Quality

of life

0.51* 0.36 0.77** 0.82** 0.75** -




**p < 0.01 level (2-tailed)

*p < 0.05 level (2-tailed)



78

Agreement

The results for agreement were similar to the correlation analysis: moderate level of

agreement between APFQ bladder domain and ICIQ-UI SF with a kappa coefficient

value of 0.56 in males and 0.51 in females. The agreement between APFQ bowel

domain and ICIQ-B subscales was low to moderate with a range of kappa values from

0.34 to 0.56 (Table 3-8). All agreements were statistically significant, except the

kappa values in females (p = 0.05).

Table 3-8: Agreement between AFPQ bladder and bowel domains, ICIQ-B, and

ICIQ-UI SF for symptomatic participants

Total Males Females

APFQ

domains

Comparison Kappa p value Kappa p value Kappa p value

Bladder

function

ICIQ-UI SF 0.53 0.003 0.56 0.01 0.51 0.05

Bowel

function

ICIQ-B

Bowel

pattern

0.40 0.001 0.45 0.007 0.34 0.05

ICIQ-B

Bowel

control

0.51 0.001 0.56 0.005 0.45 0.05

ICIQ-B

Quality of

life

0.51 0.001 0.56 0.005 0.45 0.05




Predictors

The logistic regression analysis showed that the significant predictors for bladder

symptoms were increase in age per year in males (p = 0.03) and females (p = 0.045)

and stage of cancer in males: a diagnosis of stage III CRC (26.5 OR: 95% CI 1.29 to

543.65; p = 0.03) predicted bladder symptoms in males following CRC surgery

(Table 3-9).


79

Table 3-9: Association between demographic and clinical variables and bladder and bowel symptoms in participants following surgery for

colorectal cancer

Abbreviations: 95% CI, 95% Confidence Interval.


Bladder symptoms Bowel symptoms Bladder symptoms Bowel symptoms Bladder symptoms Bowel symptoms

Odds

Ratio

(95%

CI)

p-value Odds

Ratio

(95%

CI)

p-value Odds

Ratio

(95% CI)

p-value Odds

Ratio

(95%

CI)

p-value Odds

Ratio

(95%

CI)

p-value Odds

Ratio

(95%

CI)

p-value

Age 0.88

(0.80 -

0.96)

0.006 0.97

(0.92 -

1.01)

0.14 0.85 (0.74

- 0.98)

0.03 0.96

(0.89 -

1.03)

0.22 0.80

(0.64 -

1.00)

0.045 0.97

(0.88 -

1.06)

0.45

Level of

tumour

Colon 1 1 - 1 - 1 - 1 - 1 -

Rectum 0.41

(0.05 -

3.30)

0.40 1.48

(0.27 -

8.11)

0.65 0.67 (0.01

- 36.02)

0.84 0.64

(0.05 -

8.96)

0.74 0.78

(0.01 -

47.54)

0.91 4.06

(0.18 -

91.35)

0.38

Stage of

cancer

Stage I 1 1 - 1 - 1 - 1 - 1 -

Stage II 2.05

(0.32 -

13.14)

0.45 1.18

(0.24 -

5.77)

0.84 5.13 (0.11

- 230.55)

0.40 3.87

(0.24 -

62.47)

0.34 0.71

(0.03 -

16.40)

0.83 0.72

(0.07 -

8.06)

0.79

Stage III 2.83

(0.42 -

19.10

)

0.29 0.78

(0.15 -

4.08)

0.77 26.47

(1.29 -

543.65)

0.03 2.70

(0.21 -

34.61)

0.45 0.02

(0.00 -

4.77)

0.16 0.22

(0.01 -

7.04)

0.39


80

3.5.4 Discussion

This exploratory analysis showed moderate correlations between the bladder and

bowel function domains of APFQ and the ICIQ-UI SF and ICIQ-B in patients

following surgery for CRC surgery. The positive associations observed with the

bladder and bowel function domains of APFQ and the other two symptom severity

questionnaires support the construct validity of the APFQ. The results of this study

suggest that the APFQ may be valid in the CRC population, and also that its utility

can be generalized beyond female CRC populations.

In the original validation for the APFQ, the bladder function domain score was

validated against the short version of the Urogenital Distress Inventory (UDI) in

females with pelvic floor disorders (Baessler et al., 2009), and the authors found a

significant correlation with the UDI score (Spearman’s rho 0.80; p < 0.001). The

findings of our study using a smaller cohort of males and females following surgery

for CRC suggested a significant and similar correlation of the APFQ bladder function

domain in comparison to the ICIQ-UI SF scores (total: r = 0.74; p < 0.01; male: r =

0.71; p < 0.01; female: r= 0.83; p < 0.01). The slightly lower correlation in males may

be accounted for by a relatively lower prevalence of urinary symptoms among the

majority of the males than females in the CRC populations (Lange & de Velde, 2010).

Baessler et al. validated the bowel function domain of the APFQ against the Heaton’s

bowel questionnaire, and found a high correlation between the two questionnaires

(Spearman’s rho 0.81-0.92, p < 0.001) (Baessler et al., 2009). Although the

correlations in our findings were lower (r = 0.69 - 0.78 in total cohort; r = 0.69 – 0.79

in males; r = 0.70 - 0.77 in females), it should be noted that our study may not be

directly comparable with the study by Baessler et al. due to the population differences

(Baessler et al., 2009). The inclusion of male participants and the effects of cancer and

cancer treatment (surgery, RT, CT) on bladder and bowel function in patients with

CRC (Bernard, Ouellet, Moffet, Roy, & Dumoulin, 2015; Lange et al., 2008) may

affect the comparisons.


81

Nevertheless, the moderate correlations between APFQ, ICIQ-UI SF, and ICIQ-B in

our study suggested that these questionnaires measure similar constructs in the CRC

population. Although a combination of different self-reported questionnaires on

bladder and bowel symptoms are often used in research studies to obtain a

comprehensive understanding of a patient’s condition, these are likely to be too

time-consuming and burdensome for patients and clinicians in a clinical practice

setting. The use of one questionnaire (i.e. APFQ) which is applicable to male and

female CRC populations and evaluates both bladder and bowel domains instead of

two separate questionnaires (i.e. ICIQ-UI SF and ICIQ-B) can reduce participant

burden in both research and clinical settings.

In this study, the APFQ bladder domain was significantly correlated not only with

ICIQ-UI SF total score but also with some ICIQ-B subscales in the female cohort.

One possible explanation is that urinary and faecal incontinence are not only highly

prevalent but also co-existing among women in the community (Botlero, Bell,

Urquhart, & Davis, 2011; Malykhina, Wyndaele, Andersson, De Wachter, &

Dmochowski, 2012); therefore, preoperative bladder and bowel dysfunction may

influence post-operative function (Lange et al., 2008). Nevertheless, further

evaluation is required to determine the prevalence and the impact of preoperative

bladder and bowel dysfunction in females who are scheduled to undergo CRC

surgery.

With a score of greater than or equal to one as the cut-off value for symptomatic

participants, the APFQ bladder domain had a moderate agreement with ICIQ-UI SF,

and low to moderate agreement was found between APFQ bowel domain and ICIQ-B.

A cut-off score of one was chosen based on previous validation study (Avery et al.,

2004). However, it is important to note that no cut-off values have been established

for APFQ and ICIQ-B. All of the correlations and agreements should be interpreted

with caution due to the possible over- or under-estimation of the number of

symptomatic participants and the small sample size. More research is warranted to

establish the sensitivity, specificity, and positive and negative predictive values of the

APFQ in a cancer population.


82

Our exploratory results revealed that age and stage III cancer had the potential to

predict the severity of male post-operative bladder symptoms using the APFQ bladder

domain following CRC surgery. The finding of this study on cancer stage as a

predictor of male bladder symptoms concurs with a previous study (Morino et al.,

2009), which reported that tumour stage and distance from the anal verge were

independently associated with postoperative bladder function in males. However,

Morino et al. found that age did not significantly affect bladder function (Morino et al.,

2009), which was in contrast to the finding of our study. This may be due to the

different types of surgery and the age range of the participants in the two studies.

Moreover, previous studies demonstrated that aging might be related to deterioration

in bladder function in community-dwelling men and women (Madersbacher et al.,

1998). As the preoperative bladder function was not available, our findings on the

association between age and postoperative bladder function could reflect a natural

history of bladder dysfunction and need to be confirmed with further studies.

This study has some limitations. First, as this study was a retrospective analysis of

two prospective studies, a selection bias must be considered. Second, other potential

confounding factors that may have an impact on post-operative bladder and bowel

symptoms, such as pre-operative bladder and bowel function (Fish & Temple, 2014;

Lange et al., 2008), history of childbirth and hormonal status of the female

participants (Daniels et al., 2006; Fish & Temple, 2014), were not addressed in the

study due to the lack of available pre-operative data. Moreover, given the small

sample size, it was difficult to conduct subgroup analyses to investigate the validity of

APFQ in patients who have undergone surgery for rectal cancer versus colon cancer

and those who have undergone adjuvant therapies versus no adjuvant therapies. Due

to a higher percentage of participants treated for colon cancer (82%) compared to

18% of participants with rectal cancer in our study, the findings of this study may not

be generalized to all CRC population. Lastly, the ICIQ-UI SF and ICIQ-B do not

include all bladder and bowel symptoms that could affect a patient following CRC

surgery. Despite the inherent differences between the three questionnaires and the

limitations, the relationships observed in this study were in the direction hypothesized.

This work has clinical implications for health care professionals working with the

CRC population. In view of reducing the burden for patient, researcher and clinician,


83

the APFQ would be a potentially appropriate and easy to administer instrument to

measure the severity of bladder and bowel symptoms in patients following surgery for

CRC.

3.5.5 Summary

The APFQ is moderately correlated with the ICIQ-UI SF and ICIQ-B and appears to

be a useful instrument for clinical and research use. Age may be a potential predictor

for bladder symptoms in patients following surgery for CRC. While stage III cancer

might impact upon post-operative bladder symptoms in males, more robust and

prospective studies are needed to fully understand the roles of clinical and surgical

variables as predictors of bladder and bowel symptoms in patients following CRC

surgery. Further research using larger cohorts is warranted to evaluate additional

psychometric properties including sensitivity and specificity of the APFQ in CRC to

further demonstrate the utility of the instrument within this population.

The measurement instruments described in this chapter were utilised in Study 3, 4, 5,

6, and 7 in this thesis. In the following chapter, the validity of three most commonly

used field walking tests utilized to measure functional exercise capacity was explored

to assist in choosing the most appropriate alternatives to laboratory based CPET for

use in the studies within this thesis and in clinical practice.


84

Chapter 4. How should functional exercise capacity be measured in colorectal

cancer? a pilot validation study

This study was published in 2016:

Lin K-Y, Denehy L, Frawley H.C., Dimitriadis T, Martin J, Parry S, Irving L,

Granger C.L. How should functional exercise capacity be measured in colorectal

cancer? a pilot validation study. Jacobs Journal of Physiotherapy and Exercise.

2016;2(2): 017.

Author contributions for this chapter are the following: K-YL, LD, HF, SP and CG

conceived the idea for the paper. K-YL, LD, HF and CG contributed to research

design. K-YL, TD, JM, LI and CG contributed to data acquisition. K-YL, LD, HF and

CG contributed to data analysis and interpretation. K-YL completed all statistical

analyses. K-YL wrote the first draft of the manuscript and managed manuscript

submission. All authors revised the paper and provided scientific input. All authors

approved the final version of the manuscript.

This study was supported by grant funding from the Pat Cosh Trust, Victoria,

Australia.

4.1 Introduction

This chapter will describe a prospective observational cohort pilot study undertaken to

explore the criterion validity, construct validity and clinical applicability of three field

walking tests to measure functional exercise capacity in patients who had undergone

treatment for CRC. Functional exercise capacity is an important marker in CRC

particularly given its close relationship to surgical outcomes and survival (Mayo et al.,

2011; Meyerhardt, Giovannucci et al., 2006; Meyerhardt, Heseltine et al., 2006;

Rodriguez, Hawkins, Berkowitz, & Li, 2015). It is commonly measured for risk

stratification to determine if patients are fit for surgery or radical treatment (Reilly,

1997) and is also an important common target for exercise and physiotherapy

interventions. As such a simple, inexpensive, feasible and valid measure of functional

exercise capacity is important for use in clinical practice. Field walking tests are


85

walking tests performed to measure functional exercise capacity in a clinical and

non-laboratory setting. The three most commonly used tests are the 6MWT (2002),

ISWT, and ESWT (Singh et al., 1992). However, the validity of these tests as

measures of functional exercise capacity in CRC is not well understood. As the

validity of an instrument or test is purpose-, setting- and population-specific

(Jerosch-Herold, 2005; Portney & Watkins, 2009; Talmage & Rasher, 1981), it is

important to assess the applicability and validity of these measures with respect to the

characteristics of the CRC population.


paper which has been accepted for publication.

4.1.1 Study aims and hypotheses

Aim1: To explore the criterion validity of three field walking tests (6MWT, ISWT

and ESWT) against the gold standard test (laboratory CPET) to measure functional

exercise capacity in patients who had undergone treatment for CRC

Hypothesis 1: All three field walking tests would be moderately and positively

correlated with VO2peak measured by CPET

Aim 2: To investigate the relationships of 6MWT, ISWT, ESWT, and CPET to

patient-reported physical function, respiratory function, hand grip strength, and

HRQoL, and to determine the clinical applicability and practicality of the tests

Hypothesis 2: The 6MWT, ISWT, ESWT, and CPET would be moderately correlated

with patient-reported physical function, respiratory function, hand grip strength, and

HRQoL.

4.2 Materials and Methods


86

4.2.1 Study design, setting and participants

This prospective observational cohort pilot study was conducted at a tertiary

metropolitan hospital in Melbourne, Australia from May 2014 to February 2016. The

study was approved by the Melbourne Health HREC, and written informed consent

was obtained from all participants. A copy of the HREC approval letter (HREC

2013.052) from Melbourne Health is included in Appendix 4.1. This study was

conducted and is reported according to the Strengthening the Reporting of

Observational Studies in Epidemiology (STROBE) guidelines (von Elm, Altman,

Pocock, Gotzsche, & Vandenbroucke, 2007). Participants were eligible for the study

if they had histologically confirmed diagnosis of CRC; received treatment (surgery,

CT, and/or RT) within the past six months; and had an Eastern Cooperate Oncology

Group Performance Status (ECOG-PS) score of 0–2. Exclusion criteria included

co-morbidity preventing exercise testing; insufficient English language skills to

participate; and a contraindication to CPET as recommended by the American

Thoracic Society (ATS & ACCP, 2003).

4.2.2 Procedure

Ten participants were recruited from the colorectal outpatient clinics between May

2014 and August 2015, and tested within six months of their last treatment (surgery,

CT and/or RT). Each participant completed the 6MWT, ISWT, ESWT, CPET,

hand-grip strength test, and study questionnaires on the same day. The order of testing

was managed pragmatically. Participants rested for at least one hour before CPET. In

between field walking tests, participants were given a minimum of 15 minutes rest to

ensure they had recovered (assessed by return to resting heart rate and resting Borg

score [+/- 1]) prior to completing the next test. No treatment occurred in between

tests.

4.2.3 Measures


87

Socio-demographic and medical variables were collected. Participants were asked if

they had any limitations to walking. The ECOG-PS was used to measure participants’

physical function (Oken et al., 1982).

Field walking tests

Six minute walk test (6MWT)

The 6MWT, a self-paced field walking test, was performed according to the published

American Thoracic Society guidelines (2002). Participants were asked to walk as far

as possible over a 30-meter course in 6 minutes. The total distance walked in meters

(m) was documented. The 6MWT was performed on two occasions to account for the

learning effect, and the best test result was used in analyses (Spencer et al., 2008; Wu

et al., 2003). In patients with cancer, the 6WMT is a reliable measure (intraclass

correlation coefficient [ICC] r = 0.93) (Schmidt et al., 2013).

Incremental Shuttle Walk Test (ISWT) (Department of Respiratory Medicine,

Glenfield Hospital, Leicester, UK)

The ISWT, an externally-paced incremental field walking test, was performed around

a 10-meter course according to published guidelines (Singh et al., 1992). Participants

were asked to pace according to an incremental walking speed dictated by an audio

signal, and the distance in meters was measured. The test speed increased every

minute, and the test finished when the participant was unable to maintain the required

speed or limited by dyspnoea or a heart rate >85% predicted maximum (Singh et al.,

1992). The ISWT was performed twice to account for the learning effect and the best

test result was used in analyses (McKeough et al., 2011; Singh et al., 2014). A

previous systematic review has reported good reliability (ICC > 0.75) in patients with

various diseases, such as COPD, chronic heart failure, cardiomyopathy, and cystic

fibrosis, and patients who have undergone cardiovascular, abdominal, or lung cancer

surgery (Parreira et al., 2014).


88

Endurance Shuttle Walk Test (ESWT) (Department of Respiratory Medicine,

Glenfield Hospital, Leicester, UK)

The ESWT, an externally-paced field walking test of endurance capacity, was

performed along the same course as the ISWT (Revill et al., 1999) and performed

according to published guidelines (Revill et al., 1999). The walking speed was pre-set

at the pace equivalent to 85% of the calculated VO2peak from the ISWT (Hill et al.,

2012b). Participants were instructed to walk for as long as possible until they were

unable to maintain the required speed or became breathless, and the endurance time in

seconds was recorded. The cut-off time was 20 minutes, but patients were unaware of

the time limit. A single ESWT was performed as no learning effect is reported for

ESWT (McKeough et al., 2011; Ngai et al., 2015).

Laboratory-based exercise test

Cardiopulmonary Exercise Testing (CPET)

Cardiopulmonary Exercise Testing was performed to determine VO2peak using a

Sensormedics Vmax Encore, 229D (Sensormedics, Yorba Linda, Ca, USA) exercise

system and a Ergoline Via Sprint 150P cycle ergometer (Lindenstrabe 5, 72475 Bitz,

Germany) (ATS & ACCP, 2003). The test started with two minutes of rest followed

by cycling with the workload increments selected using the equations from Jones

(Jones, 1988), and the test continued to the point of symptom-limitation (Datta,

Normandin, & ZuWallack, 2015). Heart rate, blood pressure, and SpO2 were

monitored with a 12-lead electrocardiogram using a GE Cardiosoft Version 6.51

electrocardiography system (GE Healthcare, GE Marquette Medical Systems, 8200

West Tower Ave, Milwaukee, WI 53223. USA), a sphygmomanometer, and a pulse

oximeter throughout the test and during recovery. The CPET data were calculated by

averaging the results every 30 seconds, and the percentage of predicted VO2peak was

calculated according to normative equations by Jones (Jones, 1988). Maximal patient

effort was indicated by evidence of exhaustion, attaining predicted maximal heart rate,

and attaining predicted minute ventilation (Datta et al., 2015).


89

Throughout the field walking tests and laboratory-based exercise test, patient safety

was monitored. Before and after the test, participants’ heart rate and SpO2 were

recorded with a portable pulse monitor (Datex-Ohmeda TuffSat handheld pulse

oximeter [Fairfield, CT, USA]). Dyspnoea and leg fatigue were measured with the

Modified Borg Scale (10-point scale, with 0 as ‘nothing at all’ and 10 as ‘maximal’

breathing difficulty or leg fatigue) (Kendrick et al., 2000). Participant stability

between tests was assessed by the differences in the pre-test Borg scores. The time

and number of assessors required to conduct each test, and any adverse events were

recorded.

Additional measures

Hand-grip strength was measured using a Jamar hydraulic hand-grip dynamometer

(Roberts et al., 2011). The participant was tested in the position recommended by the

American Society for Hand Therapists (Peolsson et al., 2001), and the best of three

measures was taken. Health-related quality of life was evaluated by the European

Organization for the Research and Treatment of Cancer questionnaire and CRC

module (EORTC QLQ-C30 and QLQ-CR29). All scale/single item measures range in

score from 0-100. A high score on the functional and the global quality of life scale

represents a high level of functioning and high quality of life, while a high score on

the symptom scale represents a high level of symptomatology (Aaronson et al., 1993;

Whistance et al., 2009).

A standardized data collection sheet and a questionnaire booklet were used (Appendix

4.2).

4.2.4 Statistical analyses

Data analyses were performed using the SPSS Windows Version 22.0 (SPSS,

Chicago, IL, USA). Data were assessed for normality and homoscedasticity (equality

of variance) using the Shapiro-Wilk test, and bivariate scotterplot, residual plot, and

Levene’s tests, respectively (Exposito-Ruiz, Perez-Vicente, & Rivas-Ruiz, 2010;


90

Ghasemi & Zahediasl, 2012). Descriptive statistics, such as mean and SD and number

and percentage were used to summarise data. Participant exercise stability was

assessed by comparing Borg dyspnoea scores and Borg leg fatigue scores before each

test (6MWT x 2, ISWT x 2, ESWT and CPET) using paired t-tests. Pearson’s

correlation coefficients were calculated between 6MWT distance (meters), ISWT

distance (meters), ESWT time (seconds) and CPET VO2peak (ml∙kg-1∙min-1) to assess

criterion validity (Norman, 2010). Construct validity was examined by investigating

the relationships between field walking tests, CPET, respiratory function, physical

function (ECOG-PS), hand-grip strength, and HRQoL physical function and global

health domain scores using Pearson's correlation coefficients. The strength of the

correlation was determined by the correlation coefficient values (0.00–0.30 =

negligible; 0.30–0.50 = low positive correlation; 0.50–0.70 = moderate positive

correlation; 0.70–0.90 = high positive correlation; and 0.90–1.00 = very high positive

correlation) (Mukaka, 2012; Zou et al., 2003). The relationships between the CPET

and field walking tests were further analysed using simple linear regression with the

CPET VO2peak as the dependent variable, and 6MWT distance, ISWT distance or

ESWT time as the independent variables. The differences in the test results between

participants with or without self-rated walking limitations (to determine discriminant

validity) were compared using the independent t-test. The test floor and ceiling effects

were calculated as the percentage of participants scoring at the lowest [6MWT = 0 m,

ISWT= 0 m, ESWT= 0 s] or the highest [ISWT = 1020 m, ESWT = 1200 s] possible

results, respectively. The level of significance was set at p < 0.05.

4.3 Results

A total of 103 patients were screened between July 2013 and August 2015. Thirty-five

(n = 35/103) were eligible and approached (Figure 4.1). Twenty-five patients declined

to participate; the consent rate was 29% (n = 10/35). The main reasons for decline

were “not interested” 24 % (n = 6/25) and “initially agreed but failed to attend” 20 %

(n = 5/25). A total of 10 patients with CRC were enrolled in the study (Figure 4.1).

The mean age of the study cohort was 56.2 ± 15.5 years, and 70% were female.

Socio-demographic and medical variables including age, sex, BMI, social situation,

education, and employment status, cancer stage, treatment type/status, smoking


91

history, and comorbidities measured with the simplified Colinet comorbidity score

(Colinet et al., 2005) of the enrolled participants are shown in Table 4-1. Table 4-2

presents the test results.

Figure 4.1: STROBE flow chart of the study

Consented (n = 10)

Assessed for eligibility (n = 103)

Analysed

6-minute walk test (n = 10)

Incremental shuttle walk test (n = 10)

Endurance shuttle walk test (n =10)

CPET (n =10)

1. Excluded (n = 68)

o Insufficient English language skills (n = 9)

o Extensive skeletal / visceral metastases (n

= 12)

o Not colorectal cancer (n = 7)

o Co-morbidity preventing exercise test (n =

12)

o Stage IV disease post-surgery (n = 2)

o Diceased (n = 1)

o Currently receiving chemotherapy (n = 3)

o Medically unsafe to participate in CPET (n =

6)

o Unable to contact (n = 4)

o Past inclusion date (n = 12)

2. Declined (n = 25), reasons:

o Travel (n = 3)

o Not interested (n = 6)

o Work commitments (n = 4)

o Time commitments (n = 3)

o Fatigue (n = 1)

o Patient reported they are too unwell (n = 3)

o Initially agreed but failed to attend (n = 5)

Completed testing session 1 (n = 10)

Completed testing session 2 (n = 10)


92

Table 4-1: Medical and social demographics (n = 10)

Variables Mean ± SD or n (%)

Age, years 56.2 ± 15.5

Sex, female:male 7 (70) : 3 (30)

Body mass index, kg/m2 24.6 ± 4.5

Colinet comorbidity score 1.2 ± 2.4

Smoking status

Never smoker 4 (40)

Ex-smoker 6 (60)

Cancer site

Colon 3 (30)

Rectum 7 (70)

Cancer stage

Stage I 3 (30)

Stage II 2 (20)

Stage III 5 (50)

Adjuvant treatment

Chemotherapy and radiotherapy 3 (30)

Chemotherapy only 5 (50)

No adjuvant treatment 2 (20)

Type of colorectal surgery

Colectomy 3 (30)

Anterior resection 5 (50)

Abdomino-perineal excision of rectum 2 (20)

Time since operation, days 271.6 ± 92.3

ECOG-PS, patient rated

Fully active 6 (60)

Walking but only light work 4 (40)

Self-reported limitation to walking 3 (30)

Use of a gait aid 1(10)

Physical activity levels

Sedentary (0 min/week) 1 (10)

Insufficient (1–149 min/week) 7 (70)

Sufficient (150+ min/week) 2 (20)

Time spent watching television, hours/day 3.9 ± 3.4

Social situation

Home with family 7 (70)

Home alone, independent 1 (10)

Home with supports 1 (10)

Nursing home-high level care 1 (10)

Employment status

Working full time 2 (20)

Working part time 1 (10)

Sick leave/leave of absence-temporary 1 (10)

Retired 5 (50)

Home duties 1 (10)

Highest level of education

Some primary schooling 1 (10)

Some secondary or high school 3 (30)


93

Completed secondary or high school 3 (30)

Some university 1 (10)

Completed Bachelor’s degree 2 (20) Abbreviations: %, percent; ECOG-PS, Eastern Cooperate Oncology Group - Performance status; n,

number; SD, standard deviation.

Table 4-2: Test results

Variables Mean ± SD

Field walking tests

6MWT distance, m 545.0 ± 115.2

ISWT distance, m 580.0 ± 217.7

ISWT predicted VO2peak, ml/kg/min 18.7 ± 5.4

ESWT time, seconds 698.0 ± 318.1

ESWT level, completed 13.9 ± 4.3

CPET – resting

Heart rate, beats/min 81.3 ± 14.7

Systolic blood pressure, mmHg 117.5 ± 11.8

Diastolic blood pressure, mmHg 74.0 ± 8.1

Oxygen saturation, % 97.2 ± 1.4

CPET - peak

Heart rate, beats/min 158.3 ± 22.3

Systolic blood pressure, mmHg 153.0 ± 15.1

Diastolic blood pressure, mmHg 78.0 ± 10.3

Oxygen saturation, % 96.4 ± 1.8

VO2peak, ml/kg/min 22.8 ± 6.5

VO2peak, ml/kg/min, % predicted 82.1 ± 19.7

VO2peak, L/min 1.5 ± 0.5

VO2peak, L/min, % predicted 72.0 ± 16.7

VE, L/min 66.9 ± 20.5

Work 104.0 ± 41.0

Respiratory function

FEV1, litres 2.6 ± 0.8

FEV1 % predicted 109.8 ± 17.2

FVC, litres 3.4 ± 1.2

FVC, % predicted 120.6 ± 17.1

Dominant hand-grip strength, kilograms

Female 10.3 ± 9.0

Male 23.3 ± 6.1

HRQoL

Global quality of life domain 75.0 ± 21.5

Physical function domain 90.7 ± 16.7 Abbreviations: %, percent; 6MWT, six-minute walk test; CPET, cardiopulmonary exercise test; ESWT,

endurance shuttle walk test; ISWT, incremental shuttle walk test; SD, standard deviation; VO2peak, peak

oxygen consumption; FEV1, Forced expiratory volume in 1 second; FVC, Forced vital capacity;

HRQoL, health-related quality of life.


94

Participant stability between tests

In the pre-test phase, no significant difference was found in the Borg leg fatigue

scores between each test (p > 0.05), and the mean differences between each pre-test

Borg scores were within +/- 1 (Table 4-7), suggesting patients had returned to

baseline before proceeding with the subsequent test. The pre-test Borg dyspnoea score

was also not significantly different between first and second 6MWT (p > 0.05).

However, there was a significant difference in the pre-test Borg dyspnoea score

between first and second ISWT (mean difference [95 % CI] = -0.35 [-0.69 - -0.01]

points, p = 0.045) although this difference is not considered to be clinically significant

(Crisafulli & Clini, 2010).

Criterion validity

The associations between VO2peak obtained by CPET and distance walked in the

6MWT and ISWT were significant (R2=0.68, p = 0.003; R2=0.65, p = 0.005) (Figure

4.2). No significant association was found between ESWT time and CPET VO2peak

(R2=0.36, p = 0.07) (Figure 4.2). Although a strong relationship was found between

ISWT predicted VO2peak and CPET VO2peak (ml∙kg-1∙min-1) (R2=0.65, p = 0.005, data

not in Table), the ISWT tended to under-predict VO2peak in comparison to VO2peak

measured using CPET (Table 4-2).


95

A

B


96

C

Figure 4.2: Relationship between 6MWT distance (A), ISWT distance (B), and ESWT

time (C) with CPET VO2peak.

Construct validity

The distance walked in the 6MWT was significantly correlated with ISWT (r = 0.93,

p < 0.001) (Table 4-3) and the HRQoL physical function domain score (r = 0.90, p <

0.01) (Table 4-5). High correlation also existed between the ISWT and HRQoL

physical function domain score (r=0.84, p = 0.01) (Table 4-5). No significant

correlations were found between ESWT time and other field walking test results,

respiratory function, physical function, hand-grip strength, and HRQoL. The CPET

VO2peak significantly correlated with respiratory function (FVC and FEV1) (Table 4-4)

and dominant hand-grip strength, and correlated moderately with HRQoL physical

function domain score (Table 4-5).


97

Table 4-3: Pearson’s correlations between CPET VO2peak and 6MWT distance,

ISWT distance, and ESWT time (N = 10)

6MWT

distance, m

ISWT

distance, m

ESWT time,

seconds

CPET VO2peak,

ml/kg/min

6MWT distance, m - 0.93** 0.53 0.82**

ISWT distance, m - 0.49 0.81**

ESWT time,

seconds - 0.60

CPET VO2peak,

ml/kg/min -

Abbreviations: 6MWT, six-minute walk test; CPET, cardiopulmonary exercise test; ESWT, endurance

shuttle walk test; ISWT, incremental shuttle walk test; VO2peak, peak oxygen consumption.

** p < 0.01 level (2-tailed).


time, CPET VO2peak and respiratory function

6MWT

Distance, m

ISWT Distance,

m

ESWT time,

seconds

CPET

VO2peak,

ml/kg/min

FVC, litres 0.36 0.31 0.22 0.70*

FEV1, litres 0.45 0.45 0.41 0.75*

FEV1/FVC 0.17 0.30 0.45 -0.07 Abbreviations: FEV1, Forced expiratory volume in 1 second; FVC, Forced vital capacity; 6MWT,

six-minute walk test; CPET, cardiopulmonary exercise test; ESWT, endurance shuttle walk test; ISWT,

incremental shuttle walk test; VO2peak, peak oxygen consumption.

*p < 0.05 level (2-tailed).


time, and CPET VO2peak and ECOG-PS, HRQoL physical function and global health

domain scores, and hand-grip strength

6MWT

Distance, m

ISWT

Distance, m

ESWT time,

seconds

CPET VO2peak,

ml/kg/min

Dominant hand grip

strength, kg

0.50 0.60 0.32 0.82**

HRQoL Global quality

of life domain

0.15 0.13 -0.44 -0.23

HRQoL Physical

function domain

0.90** 0.84** 0.29 0.64*

ECOG-PS -0.61 -0.58 0.09 -0.33 Abbreviations: 6MWT, six-minute walk test; CPET, cardiopulmonary exercise test; ESWT, endurance

shuttle walk test; ISWT, incremental shuttle walk test; VO2peak, peak oxygen consumption; ECOG-PS,

Eastern Cooperate Oncology Group - Performance status; HRQoL, health-related quality of life.

* Correlation is significant at the 0.05 level (2-tailed).

** Correlation is significant at the 0.01 level (2-tailed).


98

Discriminant validity is shown in Table 4-6. There was a significant difference in the

ESWT time (p = 0.04) when the cohort was dichotomized on the basis of self-rated

walking limitation into participants with and without walking limitation. The mean

difference [95% CI] was significant between participants with or without self-rated

walking limitations on the ESWT time (mean difference = -431.43 seconds, p = 0.04)

(Table 4-6).

Table 4-6: Discriminant validity: Difference between participants with or without

self-rated walking limitations in all walking tests

Tests Participants with

walking limitation

(mean ± SD)

Participants

without walking

limitation (mean ±

SD)

Mean

difference

[95%CI]

p-value

6MWT

distance, m

532.67 ± 104.33 550.29 ± 127.18 17.62 [-176.31

- 211.55]

0.84

ISWT

distance, m

553.33 ± 176.73 591.43 ± 245.32 38 .10

[-328.05 -

404.25 ]

0.82

ESWT time,

seconds

1000.00 ± 346.41 568.57 ± 215.92 -431.43

[-837.03 -

25.83 ]

0.04

CPET VO2peak,

ml/kg/min

22.93 ± 9.41 22.71 ± 5.76 -0.22 [-11.13 -

10.69 ]

0.96

Abbreviations: 6MWT, six-minute walk test; CPET, cardiopulmonary exercise test; ESWT, endurance

shuttle walk test; ISWT, incremental shuttle walk test; VO2peak, peak oxygen consumption; SD,

standard deviation; CI, confidence interval.

Clinical applicability

6MWT

No floor effect was observed in the 6MWT. The 6MWT distance ranged from

270-654 meters. From pre- to post-6MWT, there were statistically significant

increases in dyspnoea (mean difference [95 % CI] = 2.0 [1.1-2.8] points, p = 0.001)

and leg fatigue (mean difference [95 % CI] = 1.8 [0.5-3.0] points, p = 0.01) (Table

4-7). The mean ± SD time required to perform one individual 6MWT (including

set-up and instruction) was 8.5 ± 2.4 minutes.


99

ISWT

No floor or ceiling effects were observed in the ISWT. The ISWT distance ranged

from 110-890 meters, and the predicted VO2peak from this test ranged from 6.9-26.4

ml∙kg-1∙min-1. Significant increases were found from pre-ISWT dyspnoea and leg

fatigue to post-ISWT dyspnoea (p < 0.0005) and leg fatigue (p = 0.001) (Table 4-7).

The mean ± SD time required to perform one individual ISWT was 10.6 ± 3.5

minutes.

ESWT

Although no floor effect was seen in the ESWT, a ceiling effect was found with 70 %

(n = 7/10) of participants reaching the end of the test (1200 seconds). The ESWT time

ranged from 220-1200 seconds. The ESWT was performed on the ESWT tape levels

ranging from 3–16. From pre- to post-ESWT, there were statistically significant

increases in dyspnoea (mean difference [95 % CI] = 2.6 [1.7-3.5] points, p < 0.0005)

and leg fatigue (mean difference [95 % CI] = 2.3 [1.1-3.4], p = 0.002) (Table 4-7).

The mean ± SD time required to perform the ESWT was 13.1 ± 4.9 minutes.

CPET

In comparison, the time required to perform the CPET was 48.1 ± 9.4 minutes. No

adverse events were observed during the CPET. The increase in dyspnoea and leg

fatigue from pre- to post-CPET were mean difference [95 % CI] 5.0 [3.7-6.3] points

(p < 0.0005) and 5.4 [3.3-7.6] points (p < 0.0005) respectively (Table 4-7). Only one

assessor was required to perform the field walking tests, whereas the CPET required

two to three assessors.


100

Table 4-7: Changes in BORG scores with each test

Test Pre-test

mean ± SD

Post-test

mean ± SD

Mean difference

[95%CI]

p-value

Dyspnoea

6MWT 0.4 ± 0.7 2.4 ± 1.4 2.0 [1.1 - 2.8] 0.001

ISWT 0.4 ± 0.4 3.1 ± 1.0 2.8 [2.1 - 3.4] < 0.0005

ESWT 0.6 ± 0.4 3.2 ± 1.4 2.6 [1.7 - 3.5] < 0.0005

CPET 0.8 ± 1.6 5.8 ± 1.5 5.0 [3.7 - 6.3] < 0.0005

Leg fatigue

6MWT 0.8 ± 1.2 2.6 ± 1.3 1.8 [0.5 - 3.0] 0.010

ISWT 0.7 ± 0.8 3.1 ± 1.9 2.4 [1.4 - 3.4] 0.001

ESWT 0.9 ± 0.5 3.2 ± 1.8 2.3 [1.1 - 3.4] 0.002

CPET 0.5 ± 1.0 5.9 ± 2.8 5.4 [3.3 - 7.4] < 0.0005 Abbreviations: 6MWT, six-minute walk test; CPET, cardiopulmonary exercise test; ESWT, endurance

shuttle walk test; ISWT, incremental shuttle walk test; SD, standard deviation; CI, confidence interval.

4.4 Discussion

This is the first study to explore the association of three common field walking tests

with CPET, the gold standard measure of functional exercise capacity, in patients with

CRC. Our results demonstrate significant relationships between the distance walked

in both the 6MWT and the ISWT and the VO2peak achieved on the CPET. This result

corresponds to findings reported in previous studies in patients with mixed cancer

diagnoses (26% CRC) (Schmidt et al., 2013), operable lung cancer (Win et al., 2006),

and non-small cell lung cancer (Granger, Denehy et al., 2015), and suggests that

6MWT and ISWT are both valid tests for assessing functional exercise capacity in

patients with CRC. As well as the similarity of our findings with previous studies in

cancer populations (Granger, Denehy et al., 2015; Schmidt et al., 2013; Win et al.,

2006), the criterion validity of the 6MWT and ISWT in our study is also comparable

to the studies in patients with COPD (Hill et al., 2012a; Luxton, Alison, Wu, &

Mackey, 2008), pulmonary arterial hypertension (Mainguy et al., 2014), and obesity

(Di Thommazo-Luporini et al., 2015). Therefore, both 6MWT and ISWT are useful

tests for the evaluation of functional exercise capacity in cancer and non- cancer

populations. Given the broad applicability and simplicity of 6MWT and ISWT, our

study adds further evidence to support their use by physiotherapists in the clinical and

research settings worldwide. There was no significant relationship between ESWT

and CPET. This could be expected since CPET is a test of exercise response involving


101

cardiorespiratory, musculoskeletal, neuropsychological, and haematological systems

(ATS & ACCP, 2003), while ESWT measures physical endurance only. Further, there

was a large ceiling effect (70%) for the ESWT (Witham, Sugden, Sumukadas,

Dryburgh, & McMurdo, 2012) and these findings indicate that the ESWT is not an

appropriate alternative to CPET and limited for use in this cohort. Therefore, our

finding, which showed a significant difference in the ESWT time between participants

with or without walking limitation, should be interpreted with caution. Further studies

with larger sample size are warranted to confirm this.

Although VO2peak measured by CPET is the gold standard for cardiorespiratory fitness

(ATS & ACCP, 2003), it is not commonly measured in CRC; whereas, despite lack of

proven validity to date, 6MWT is the most commonly used field walking test in CRC

research (Gillis et al., 2015; Lee et al., 2015; Li et al., 2013; Tomruk, Karadibak,

Yavuzsen, & Akman, 2015). Our results showed that compared to CPET, 6MWT and

ISWT required less time to complete (less than 15 minutes), fewer personnel to

conduct the test (only one assessor needed), and were safe for the patients. The

6MWT and ISWT may be useful and simpler alternatives to CPET in terms of the

time, costs and the equipment required in a clinical setting.

Furthermore, the 6MWT and ISWT measure a similar construct to each other as

shown by the high correlation between them. Nevertheless, use of CPET provides

more accurate physiological data and would be needed in some settings. For example,

preoperative use of CPET allows identification of patients with CRC at high risk of

requiring postoperative critical care unit admission (Chan, Pathak, Smart, Batchelor,

& Daniels, 2015). Moreover, our findings showed that VO2peak was moderately to

highly correlated to respiratory function, dominant hand-grip strength, and HRQoL

physical function domain, which is consistent with previous studies in population with

cardiopulmonary disease (Hager & Hess, 2005; Kato, Rodgers, Stickland, & Haennel,

2012; Tzani et al., 2010).

The results of this exploratory study demonstrate a significant relationship between

6MWT and ISWT, with the physical function domain of the EORTC QLQ-C30,

suggesting that greater functional exercise capacity is associated with better


102

self-reported physical function. Our findings are in line with previous studies, which

found significant correlations between 6MWT distance and HRQoL physical

well-being in CRC survivors (Lee et al., 2015), and ISWT distance and physical

functioning domain of the Short Form-36 health survey in patients with heart disease

(Costa et al., 2014). As the primary goal of physiotherapy is frequently to assist

patients to restore normal function or maximise residual function in order to prevent

limitations in activities of daily living in the long term (Higgs, Refshauge, & Ellis,

2001), our findings support physiotherapists to confidently use 6MWT and ISWT in

their assessment of function in CRC population in clinical practice. Although not

assessed in our study, the 6MWT and ISWT are known to be sensitive and responsive

to physiotherapy intervention in cardiorespiratory diseases (Bellet, Adams, & Morris,

2012; Fotheringham et al., 2015; Lee et al., 2015; Taylor, Frost, Taylor, & Barker,

2001); therefore, we hypothesize this may be the case in CRC. Further studies are

needed to investigate this. The results of our study may also inform future studies to

examine the effects of a physiotherapy program (e.g. a cardiopulmonary rehabilitation

program) in patients following surgery for CRC (Hubbard et al., 2016).

Physical function measured with ECOG-PS has been found to be the only predictor of

functional exercise capacity assessed by 6MWT in patients with CRC (Tomruk et al.,

2015). Eastern Cooperate Oncology Group Performance Status is frequently used by

clinicians to determine eligibility for treatment and prognosis of various types of

cancer (Correa et al., 2012; Sargent et al., 2009; Suh, Leblanc, Shelby, Samsa, &

Abernethy, 2011). However, our findings showed that there was no significant

relationship between ECOG-PS and field walking tests, or CPET measures, which

suggests that ECOG-PS is not interchangeable with these tests. Therefore, field

walking tests or CPET are needed for accurate assessment of functional exercise

capacity. Furthermore, it should be noted that the ECOG-PS was patient-rated in our

study; whereas, it has often been scored by clinicians in clinical practice and research

trials (Atkinson et al., 2015). The lack of congruency between patient-rated and

physician-rated ECOG-PS has been documented in the literature (Ando et al., 2001;

Dajczman et al., 2008). As better performance status at diagnosis is related to better

survival in patients with CRC (Eker et al., 2015), the relationships between ECOG-PS


103

and functional exercise capacity in CRC should be clearly elucidated by future studies

with a larger sample size

Our study is strengthened by robust methodology performed following STROBE

guidelines (von Elm et al., 2007), conduct of testing over a full day (ensuring patients

are stable) and the assessment of participant stability between each test. In addition,

tests were performed according to published guidelines (ATS & ACCP, 2003; 2002;

Miller et al., 2005; Revill et al., 1999; Singh et al., 1992). As an exploratory study, the

small sample size is our primary limitation. A larger trial is warranted to confirm the

validity of the field walking tests in CRC. Moreover, there were more females and

patients who had undergone treatment for rectal cancer in our study, which affects the

generalizability of our findings. Due to the lack of randomisation of the testing order,

an order bias must be considered, however we assessed stability between tests to

account for this. Although rest periods were provided between tests, there was a small

statistically significant difference in pre-ISWT Borg dyspnoea between the first and

second ISWT; this may have impacted upon the test results.

Despite the limitations, this preliminary evidence has clinical implications for health

care professionals working with the CRC population. In view of reducing the burden

for patient, researcher and clinician, the 6MWT and ISWT would be potentially valid,

feasible, and applicable to measure the functional exercise capacity in patients with

CRC. Our results also provide a rationale for using the field walking tests in future

studies in CRC, and inform further exploration into the potential effectiveness of

post-operative cardiopulmonary rehabilitation in this population.

4.5 Summary

The 6MWT and ISWT appear to be feasible alternative tests to CPET in the

evaluation of functional exercise capacity in patients with CRC. The distances walked

in both the 6MWT and ISWT are significantly associated with CPET VO2peak and

highly-correlated with HRQoL physical function domain. Both 6MWT and ISWT are

simple, quick and safe to perform; and do not have a floor or ceiling effect in CRC

population. However, the small sample size limits the interpretation of our results,


104

hence further studies involving larger sample sizes are required to confirm the

findings of this pilot study.

As the findings of this study demonstrated that 6MWT is a valid test for functional

exercise capacity in patients with CRC, it was used to measure changes in functional

exercise capacity before and after an oncology rehabilitation program in Study 4. The

next chapter describes changes in pelvic floor symptoms, physical activity levels,

psychological status and HRQoL in patients with CRC from pre- to six months

post-operatively.

Chapter 5. Pelvic floor symptoms, physical and psychological outcomes of patients following surgery

for colorectal cancer

105

Chapter 5. Pelvic floor symptoms, physical and psychological outcomes of

patients following surgery for colorectal cancer

This study is under review for publication:

Lin K-Y, Denehy L, Frawley H.C., Wilson L, Granger C.L. (2016). Pelvic floor

symptoms, physical and psychological outcomes of patients following surgery for

colorectal cancer. Physiotherapy Theory and Practice. Under review. Submitted

September 2016.

Author contributions for this chapter are the following: K-YL, LD, HF and CG

conceived the idea for the paper. K-YL, LD, HF and CG contributed to research

design. K-YL, LW and CG contributed to data acquisition. K-YL, LD, HF and CG


CG obtained project funding. K-YL wrote the first draft of the manuscript and

managed manuscript submission. All authors revised the paper and provided scientific

input. All authors approved the submitted version of the manuscript.

This study was supported by grant funding (GIA-00038-2014) from the Royal

Melbourne Hospital Home Lottery Research Grant in Aid - Allied Health, Victoria,

Australia.

5.1 Introduction

This chapter will describe a prospective observational study to prospectively assess

pelvic floor symptoms and physical and psychological outcomes in patients before

and up to six months after surgery for CRC. Despite the high prevalence of pelvic

floor symptoms in the community and in patients before and following rectal cancer

surgery (Bregendahl, Emmertsen, Lous, & Laurberg, 2013; Contin et al., 2014; John

et al., 2011; Maris et al., 2013; Murata, Brown, Raval, & Phang, 2008; Scheer et al.,

2011), only two small studies have shown that patients with colon cancer also suffer

from pelvic floor dysfunction following surgery (Phipps et al., 2008; Tomoda &

Furusawa, 1985). Furthermore, limited evidence is available regarding change of

pelvic floor symptoms (bladder, bowel, and sexual symptoms) and functional



106

outcomes over time in CRC patients. As we seek to improve survivorship outcomes

for this population, it is important to understand the natural history of changes in

pelvic floor symptoms in patients who have undergone CRC surgery including any

potential natural recovery of physical and psychological status, in order to inform

clinical practice and research studies.


paper which is currently under review with the Physiotherapy Theory and Practice

journal.


Primary aim

Aim 1: To prospectively assess pelvic floor symptoms in patients before and up to six

months after surgery for CRC.

Hypothesis 1: There would be deterioration in pelvic floor symptoms 6 months after

CRC surgery compared to pre-operative status.

Secondary aim

Aim 2: To assess PA levels, psychological outcomes, and HRQoL in patients before

and up to six months after surgery.

Hypothesis 2: There would be deterioration in PA levels, HRQoL and increased

anxiety and depression 6 months after CRC surgery compared to pre-operative status.


5.2.1 Study design and participants



107

This was a prospective observational study. Participants were eligible if they had

histologically confirmed stage I-III CRC and were undergoing CRC surgery. Patients

were excluded if they required a permanent ostomy, had insufficient English language

skills to participate, or had severe physical/psychiatric impairments. Participants were

recruited through Royal Melbourne Hospital and Melbourne Private Hospital between

October 2013 and August 2015. Potentially eligible patients were identified by the

treating surgeons or colorectal liaison nurse, who asked patients for their permission

to be contacted by a member of the research team. The researcher explained the study

and invited patients to participate. Written informed consent was obtained from all

participants. The study was approved by the Melbourne Health and Melbourne Private

Hospital HREC (number 2013.199) (Appendix 5.1).

5.2.2 Outcome measures

Outcomes were evaluated before and 6 months after surgery. In a subset of

participants (n=17), measures were also performed 6 weeks after surgery, to compare

the short-and medium-term changes in outcome measures over time. A questionnaire

booklet (Appendix 5.2) was given to participants at each time-point.

Pelvic floor symptoms

Pelvic floor symptoms were assessed using the APFQ (Baessler et al., 2010), ICIQ-B

(Cotterill et al., 2011) and ICIQ-UI SF (Avery et al., 2004). The APFQ is a valid and

reliable instrument consisting of 42 questions across 4 domains (bladder, bowel, and

sexual function and pelvic organ prolapse) (Baessler et al.). Scores within each

domain are divided by the number of relevant questions and multiplied by 10; thus,

the scores range from 0 to 10 for each domain, giving a maximum total score of 40

(higher scores represent worse severity/symptoms) (Baessler et al., 2009). ICIQ-B

was used in addition to APFQ to obtain more comprehensive evaluation of bowel

symptoms. ICIQ-B is a validated non-gender-specific questionnaire developed to

evaluate anal incontinence symptoms and impact on HRQoL. The ICIQ-B contains a

total of 21 questions, 17 of which are scored and form 3 domains: bowel pattern

(score range 1-21), bowel control (score range 0-28), and HRQoL (score range 0-26).



108

Four unscored items include other bowel symptoms and sexual impact (Cotterill et al.,

2011). Higher scores on the ICIQ-B represent worse bowel symptoms. As the APFQ

has only been validated in female populations (Baessler et al., 2010), the ICIQ-UI SF,

a validated non-gender-specific questionnaires, was introduced later in the study to

evaluate urinary incontinence symptoms. The ICIQ-UI SF consists of three scored

items related to frequency and amount of urinary incontinence and HRQoL and a

self-diagnostic item, which is not scored. An overall ICIQ-UI SF score is calculated

as the summation of the three scored items. Urinary incontinence is defined as either

absent (score 0) or present (score ≥ 1) on the ICIQ-UI SF (Avery et al., 2004).

Physical activity levels

The short form version of the IPAQ-SF was used to assess PA levels over the

previous 7 days. This self-report questionnaire measures frequency (days per week)

and duration (minutes per day) of PA (vigorous, moderate, and walking) and has

acceptable reliability and validity (Craig et al., 2003). The total IPAQ score in

MET-minutes per week is the summation of walking (3.3 MET), moderate activity

(4.0 MET), and vigorous (8.0 MET) activity minutes per week. Total IPAQ scores are

classified as “low” (not meeting the criteria for moderate-intensity and

vigorous-intensity activity categories), “moderate” (achieving at least 600

MET-minutes/week) and “high” (achieving at least 3000 MET-minutes/week) (IPAQ

Research Committee, 2005).

Psychological outcomes

Anxiety and depression were screened with the 14-item HADS, which is composed of

an anxiety subscale and a depression subscale. Each subscale is scored from 0 to 21.

The HADS has high internal consistency in patient populations including cancer

(Zigmond & Snaith, 1983).

Health-related quality of life



109

Health-related quality of life was evaluated by the EORTC QLQ-C30 and the

QLQ-CR29. As a supplement to EORTC QLQ-C30, QLQ-CR29 consists of 29

questions assessing the CRC-specific functional and symptom scales, such as,

gastrointestinal symptoms, pain, problems with micturition, symptoms with/without

stoma, and sexual function. All scale/single item measures of EORTC QLQ-C30 and

QLQ-CR29 range in score from 0-100. Higher scores on the functional and the global

quality of life scales represents higher level of functioning and higher HRQoL, while

higher scores on the symptom scales represents a higher levels of symptomatology.

The EORTC QLQ-C30 and QLQ-CR29 have good validity and reliability (Aaronson

et al., 1993; Whistance et al., 2009).

Socio-demographic and medical variables were collected including age; sex; BMI;

social situation; education, employment, marital, smoking and hormonal status

(female only); cancer stage; treatment type/status; length of in-patient stay; and the

ECOG-PS (Oken et al., 1982).

5.2.3 Statistical analysis

Data analyses were performed using the Statistical Package for Social Sciences

version 20.0 for Windows. Data were assessed for normality using

Kolmogorov-Smirnov (Ghasemi & Zahediasl, 2012). Descriptive statistics, such as

mean and SD, and number and percentage were used to summarize data. Paired-t tests

were used to compare changes in outcomes of interest before and 6 months after

surgery. A subgroup analysis (n=17) using repeated measures analysis of variance

(ANOVA) with Bonferroni post hoc comparisons was performed to compare changes

in outcome variables over three assessment time points (before surgery, 6-week after

surgery, and 6-month after surgery). All analyses were tested with a significance level

of p < 0.05. Data were also compared with published population norms for APFQ

(Baessler et al., 2009), ICIQ-UI SF (Osuga, Okamura, Ando, & Shimokata, 2013),

IPAQ (Tomioka, Iwamoto, Saeki, & Okamoto, 2011), HADS (Crawford, Henry,

Crombie, & Taylor, 2001) and EORTC QLQ-C30 (Hinz, Singer, & Brahler, 2014).



110

Sample size requirement was estimated from a previous study (Baessler et al., 2009).

Twenty-three participants were needed for a mean change (SD) of 1.0 ± 1.7 in the

bowel domain score of the APFQ with a power of 0.8 and alpha 0.05 (Hozo,

Djulbegovic, & Hozo, 2005). Allowing for 30% attrition, a total of 30 participants

was sought.

5.3 Results

One hundred and twenty-three patients were assessed for eligibility over the 22 month

recruitment period, 56 patients were ineligible and 56 were approached. The consent

rate was 53.6%. The main reasons for decline were “inability to read/write English”

31 % (n = 8/26) and “too busy” 27 % (n = 7/26). A total of 30 patients with CRC were

recruited (Figure 5.1).

Demographic characteristics are shown in Table 5-1. Fifty-three percent were males,

and 67% and 33% had a diagnosis of colon cancer and rectal cancer respectively.

Thirteen percent of the cohort received chemoradiotherapy before surgery, and 50%

received CT after surgery. The most common types of surgery were right

hemicolectomy (30%), HAR (27%), and ultra-low anterior resection (27%) (Table

5-1). None of the participants were referred to the local continence service or exercise

rehabilitation programs following surgery.



111

Figure 5.1: Flow of patients throughout the study

Total recruited (n =30)


Six weeks post-op assessment (T2): (n = 17/20)

Six months post-op assessment (T3): (n =

25/30)

Data available for analysis:

T1: n = 30

T2: n = 17

T3: n = 25

Excluded (Total = 93):

1. Ineligible (n = 56):

o Permanent stoma (n = 3)

o Stage IV (n = 30)

o Inability to read/write English (n = 19)

o Physical / cognitive impairment (n = 4)

2. Eligible but not recruited (n = 37):


o Inability to read/write English (n = 8)

o Too busy (n = 7)

o Too unwell (n = 1)


o Do not want to disclose personal information (n

= 2)

o Missed (n = 11)

Pre-operative assessment (T1):

(n = 30)

Lost to follow-up: (n = 3)

o Unable to contact n = 3

Lost to follow-up: (n = 5)

o Deceased n = 1

o Unable to contact

n = 4

Agreed to short term (6-week) follow-up assessment (n = 20)



112

Table 5-1: Demographic and medical data at baseline (n = 30)

Variables Mean ± SD or

n (%)

Age (mean, SD) 56.0 (15.2)

Sex

Female 14 (46.7%)

Male 16 (53.3%)

BMI (mean, SD)

Total 28.4 (5.9)

Female 28.0 (5.7)

Male 28.7 (6.4)

Level of tumour

Colon 20 (66.7%)

Rectum 10 (33.3%)

Cancer stage

I 6 (20%)

II 11 (36.7%)

III 10 (33.3%)

Recurrent cancer 2 (6.7%)

Missing 1 (3.3%)

Neo- / adjuvant treatments

Pre-operative

Chemotherapy and

radiotherapy

4 (13.3%)

No neoadjuvant therapy 26 (86.7%)

Post-operative

Chemotherapy 15 (50%)

No adjuvant therapy 14 (46.7%)

Missing 1 (3.3%)

Length of in-patient stay

(days) (median, IQR)

8.0 (5-15)

Type of surgery

Right hemicolectomy 9 (30%)

Subtotal or total colectomy 3 (10%)

Abdominoperineal

resection/excision

2 (6.7%)

High anterior resection 8 (26.7%)

Ultra-low anterior

resection

8 (26.7%)

Social situation

Home alone, independent 9 (30%)

Home with family 19 (63.3%)

Home with supports 2 (6.7%)

Employment status

Working full time 13 (43.3%)

Not employed/taking time

off work

3 (10%)

Retired 7 (23.3%)

Home duty 5 (16.7%)



113

Studying 1 (3.3%)

Other 1 (3.3%)

Education

No formal schooling 1 (3.3%)

High school or less 11 (36.7%)

Some college or university 11 (36.7%)

Completed Bachelor’s

degree

5 (16.7%)

Completed Masters or PhD

degree

1 (3.3%)

Other 1 (3.3%)

Smoking status

Never smoked 17 (56.7%)

Ex-smoker 9 (30%)

Missing 4 (13.3%)

ECOG performance status

Fully active 20 (66.7%)

Walking, but only can do

light work

8 (26.7%)

Rest in bed LESS than half

the day, do not work but

can care for self

2 (6.7%)

Hormonal status (n = 14)

Menstruating regularly 3 (21.4%)

Post-menopausal 11 (78.6%) Abbreviation: IQR, interquartile range; SD, standard deviation; n, number; %, percent; ECOG, The

Eastern Cooperative Oncology Group; PhD, Doctor of Philosophy.

The outcomes of the study population and the published normative values – to act as a

reference point – are shown in Tables 5-2 and 5-4. Table 5-3 reports the number of

participants categorized according to level of severity of bladder and bowel symptoms

and PA, which are the first three major outcomes of interest.

Chapter 5. Pelvic floor symptoms, physical and psychological outcomes of patients following surgery for colorectal cancer

114

Table 5-2: Pelvic floor symptoms, physical activity levels, and psychological outcomes

Community values T1 (n = 30)

(mean, SD)

T2 (n = 17)

(mean, SD)

T3 (n = 25)

(mean, SD)

Repeated

Measure

ANOVA (n =

17): p-value

T1-T3 mean

difference (n =

25)

Paired t-test (n

= 25): p-value

APFQ Bladder

(scale: 0 – 10) a

0.6 (0 – 4.7)

(Baessler et al., 2009)

0.99 (1.24) 0.56 (0.72) 0.83 (1.16) 0.54 -0.08 (0.65) 0.55

APFQ Bowel

(scale: 0 – 10) a

0.6 (0 – 7.3)


1.63 (1.58) 0.92 (0.88) 0.99 (1.07) 0.48 -0.31 (1.26) 0.24

APFQ Prolapse

(scale: 0 – 10) a

0 (0 – 3.3)

(Baessler et al.,

2009)

0.43 (1.16),

n = 14

0.30 (0.68),

n = 9

0.05 (0.18),

n = 14

0.47 -0.38 (1.00),

n = 14

0.18

APFQ Sexual

(scale: 0 – 10) a

1.4 (0 – 5.7)

(Baessler et al.,

2009)

0.41 (1.05) ,

n = 14

0.11 (0.21) ,

n = 9

0.14 (0.35),

n = 14

0.76 -0.27 (1.07),

n = 14

0.36

APFQ Total

(scale: 0 – 40) a

3.4 (0 – 15.0)


3.24 (4.15) ,

n = 14

1.93 (1.23) ,

n = 9

1.81 (1.93),

n = 14

0.23 -1.43 (2.58),

n = 14

0.06

ICIQ-B Bowel

Pattern (scale: 1

– 21) a

NA 5.70 (2.68) 5.75 (2.96) 5.74 (2.79) 0.71 0.11 (2.71) 0.87

ICIQ-B Bowel

Control (scale: 0

– 28) a

NA 4.03 (5.72) 2.67 (4.25) 2.47 (2.55) 0.62 -0.84 (3.69) 0.33

ICIQ-B Quality

of life (scale: 0

– 26) a

NA 4.53 (6.54) 4.17 (6.75) 4.16 (6.66) 0.44 0.79 (4.98) 0.50

ICIQ-UI SF 0.35 (1.39) (Osuga 0.65 (1.90), 0.40 (1.30), 0.82 (1.63), 0.63 -0.31 (2.32), n = 0.64


115

Total (scale: 0 –

21) a et al., 2013) n = 17 n = 15 n = 17 13

IPAQ Vigorous

(MET-mins/wee

k) b

NA 2350.35

(6474.40)

437.65

(1430.56)

460.00

(1134.35)

0.50 -375.65

(4265.61)

0.68

IPAQ Moderate

(MET-mins/wee

k) b

NA 912.41

(2495.36)

516.47

(1214.83)

980.87

(2713.01)

0.21 782.73

(2621.52)

0.18

IPAQ Walking

(MET-mins/wee

k) b

NA 1186.78

(1940.01)

1136.56

(1599.61)

1103.85

(2115.88)

0.87 56.83 (2161.45) 0.91

IPAQ Total

(MET-mins/wee

k) b

Men: 2160.9

(1180.6, 4108.7)

Women:

1452.2

(724.5, 2686.8)

(Tomioka et al., 2011)

3180.11

(5928.35)

2090.68

(3448.06)

2480.05

(4783.54)

0.48 146.83

(2551.75)

0.81

HADS Anxiety

(scale: 0 – 21) a

6.14 (3.76)

(Crawford et al., 2001)

6.17 (3.56) 5.47 (3.36) 4.72 (3.67) 0.20 -1.25 (3.33) 0.08

HADS

Depression

(scale: 0 – 21) a

3.68 (3.07)

(Crawford et al., 2001)

3.35 (2.55) 4.24 (4.05) 3.80 (3.43) 0.33 0.50 (2.86) 0.40

Abbreviation: T1, Time-point 1 (baseline); T2, Time-point 2 (6 weeks after surgery); T3, Time-point 3 (6 months after surgery); ANOVA, Analysis of variance; APFQ,

Australian Pelvic Floor Questionnaire; ICIQ-B, International Consultation on Incontinence Questionnaire-Bowel Module; ICIQ-UI SF, International Consultation on

Incontinence Questionnaire Short Form Questionnaire for urinary incontinence; IPAQ, International Physical Activity Questionnaire; MET, metabolic equivalent;

HADS, Hospital Anxiety and Depression Scale; SD, standard deviation; NA, not available.

A Higher score indicates worse severity/symptoms

b Higher score indicates higher physical activity levels



116

Table 5-3: Number of participants categorized according to level of severity of

bladder and bowel symptoms and physical activity, n (%)

Variables T1 (n = 30)

n (%)

T2 (n = 17)

n (%)

T3 (n = 25)

n (%)

Symptomatic-bladdera

APFQ bladder score ≥

1

11 (36.7%) 3 (17.6%) 6 (24.0%)

ICIQ-UI SF Total ≥ 1 2 (11.8%), n = 17 2 (13.33%), n =

15

4 (23.5%), n = 17

Symptomatic-bowela

APFQ bowel score ≥ 1 18 (60.0%) 8 (47.1%) 11 (44.0%)

ICIQ-B bowel pattern

≥ 1

29 (96.7%) 12 (70.6%) 18 (72.2%)

ICIQ-B bowel control

≥ 1

18 (60.0%) 8 (47.1%) 13 (52.0%)

ICIQ-B quality of life

≥ 1

19 (63.3%) 10 (58.8%) 11 (44.0%)

IPAQ-Totalb

Low 11 (42.3%) 8 (47.1%) 9 (47.4%)

Moderate: at least 600

MET-min/week

8 (30.8%) 5 (29.4%) 6 (31.6%)

High: at least 3000

MET-min/week

7 (26.9%) 4 (23.5%) 4 (21.1%)

Abbreviation: T1, Time-point 1 (baseline); T2, Time-point 2 (6 weeks after surgery); T3, Time-point 3

(6 months after surgery); APFQ, Australian Pelvic Floor Questionnaire; ICIQ-B, International

Consultation on Incontinence Questionnaire-Bowel Module; ICIQ-UI SF, International Consultation on

Incontinence Questionnaire Short Form Questionnaire for urinary incontinence; IPAQ, International

Physical Activity Questionnaire; MET, metabolic equivalent; n, number; %, percent.

A Higher score indicates worse severity/symptoms

b Higher score indicates higher physical activity levels


There were no statistically significant changes in the bladder (APFQ bladder domain

and ICIQ-UI SF) or bowel symptom scores (APFQ bowel domain and ICIQ-B) from

pre-operatively to 6-month post-operatively (Table 5-2). Changes in symptom status

are shown in Table 5-3. Prior to surgery, 37% of the participants had an APFQ

bladder score ≥ 1 and were thus classified as ‘symptomatic’. Six months after surgery,

this had declined to 24% (p > 0.05). In contrast to the APFQ results, the percentage of

participants who were symptomatic on the ICIQ-UI SF doubled (12% to 24%) from

pre-operatively to 6 months post-operatively, however this change was

non-significant (p > 0.05). Furthermore, as the ICIQ-UI SF was introduced later in the

study, there were a smaller number of participants compared to the APFQ. The



117

percentage of participants with bowel symptoms measured using APFQ decreased

from 60% pre-operatively to 44% of the participants 6 months after surgery (p >

0.05).

Psychological outcomes and PA levels

No significant changes were found in the HADS anxiety and depression scores and

PA levels assessed with the IPAQ from pre- to 6 months post-surgery (Table 5-2).

The percentage of participants engaged in low PA levels increased slightly from

42.3% pre-operatively to 47.4% at 6 months post-operatively (Table 5-3).


The results of the changes in HRQoL scores over time are shown in Table 5-4. Six

months after surgery, patients had significantly less abdominal pain (mean difference

[SD] = -15.3 ± 31.1, p = 0.02) compared to pre-operative levels. However hair loss

(mean difference = 20.8 ± 30.8, p = 0.003) and faecal incontinence (mean difference

= 15.3 ± 32.6, p = 0.03) were significantly worse. The changes in anxiety, hair loss,

symptoms of peri-anal skin soreness, abdominal pain, faecal incontinence, stool

frequency, and embarrassment by bowel movement exceeded the minimal clinically

meaningful differences on the EORTC (≥ 10 points) (Osoba et al., 1998).

5.3.1 Subgroup analysis over three assessment time points (before surgery,

6-week after surgery, and 6-month after surgery)

From pre-operatively to 6 weeks post-operatively, the EORTC QLQ C-30 role

functioning (performing work or hobbies) (Figure 5.2) and QLQ-CR29 hair loss were

significantly worse; whereas, the QLQ-CR29 anxiety and urinary frequency were

significantly improved (Table 5-4). From 6 weeks to 6 months after surgery, the

anxiety and urinary frequency as measured with QLQ-CR29 were significantly worse;

the EORTC QLQ C-30 emotional functioning and QLQ-CR29 blood and mucus in

stool improved significantly (Table 5-4).



118

Figure 5.2: Bar graph showing mean scores of role functioning for pre-and

post-operative assessments

0

20

40

60

80

100

120

Pre-surgery 6 weeks post-surgery 6 months post-surgery

QLQ

-C3

0 r

ole

fu

nct

ion

ing

sco

re

Time-point


119

Table 5-4: Health-related quality of life outcomes

Community

value (Hinz et

al., 2014)

T1 (n=30)

(mean,

SD)

T2 (n=17)

(mean, SD)

T3 (n=25)

(mean, SD)

Repeated

Measure

ANOVA

p-value

(n=17)

Post-hoc T1-T3

mean

difference

(n=25)

Paired

t-test

p-valu

e

(n=25)

EORTC QLQ C-30

Global QoLa 75.0 (19.6) 65.81

(23.08)

59.80

(25.21)

63.67

(26.01)

0.65 NA -3.82

(29.89)

0.54

Physical functioninga 92.2 (15.1) 82.99

(21.72)

72.94

(22.17)

80.00

(20.46)

0.08 NA -1.39

(16.33)

0.68

Role functioning a 90.4 (20.2) 77.01

(31.63)

54.90

(30.48)

76.00

(28.50)

0.01 T1-T2 :

p=0.007

T2-T3 : p

=0.074

T1-T3 : p

=1.000

-4.86

(28.01)

0.40

Emotional functioning a 83.5 (19.7) 75.00

(26.07)

72.55

(21.60)

84.33

(17.73)

0.04 T1-T2:

p=1.000

T2-T3:

p=0.046

T1-T3:

p=0.183

9.38

(26.62)

0.10

Cognitive functioninga 93.5 (14.5) 80.46

(27.48)

83.33

(25.00)

86.67

(18.63)

0.66 NA 3.47

(24.07)

0.49

Social functioning a 93.4 (17.2) 79.31

(27.33)

63.73

(26.51)

74.00

(28.09)

0.19 NA -7.64

(30.29)

0.23

Fatigueb 15.5 (21.6) 36.78

(30.15)

39.87

(23.91)

32.00

(24.91)

0.54 NA -5.56

(31.77)

0.40


120

Nausea and vomitingb 2.2 (8.9) 8.62

(15.82)

15.69

(26.66)

14.00

(20.23)

0.54 NA 6.25

(24.48)

0.22

Painb 16.7 (24.2) 21.26

(31.46)

28.43

(28.11)

18.00

(24.96)

0.28 NA -2.78

(30.56)

0.66

Dyspnoeab 7.5 (19.3) 17.24

(27.63)

9.80

(15.66)

18.67

(25.60)

0.34 NA 0.00

(29.49)

1.00

Insomniab 12.4 (23.3) 25.29

(36.36)

25.49

(34.42)

25.33

(30.85)

0.72 NA 2.78

(33.93)

0.69

Appetite lossb 3.8 (13.3) 22.99

(25.36)

25.49

(34.42)

14.67

(23.73)

0.59 NA -4.17

(28.34)

0.48

Constipationb 2.2 (10.3) 14.94

(27.58)

7.84

(18.74)

10.67

(20.91)

0.53 NA -2.78

(37.96)

0.72

Diarrhoeab 2.5 (11.6) 19.54

(26.00)

11.77

(26.20)

12.00

(21.26)

0.64 NA -5.56

(27.22)

0.33

Financial difficultiesb 4.8 (16.6) 21.84

(27.13)

29.41

(38.88)

28.00

(34.26)

0.12 NA 8.33

(26.47)

0.14

QLQ-CR29

Body imagea NA 86.97

(15.73)

77.78

(21.52)

78.24

(24.40)

0.06 NA -7.87

(18.96)

0.05

Anxietya NA 47.13

(30.23)

90.20

(25.72)

59.72

(25.97)

<0.001 T1-T2:

p=0.001

T2-T3:

p=0.042

T1-T3:

p=0.391

11.11

(32.10)

0.10

Weighta NA 77.01

(23.74)

66.67

(23.57)

69.44

(27.66)

0.96 NA -5.56

(34.98)

0.45

Urinary frequencyb NA 31.61 0.98 29.17 <0.001 T1-T2: -3.47 0.44


121

(23.29) (14.99) (21.00) p=0.001

T2-T3:

p=0.003

T1-T3:

p=0.793

(21.41)

Blood and mucus in

stoolb NA 12.64

(21.20)

7.84

(10.40)

2.08

(7.47)

0.02 T1-T2:

p=1.000

T2-T3:

p=0.042

T1-T3:

p=0.070

-8.33

(20.26)

0.06

Stool frequencyb NA 15.52

(29.19)

33.33

(39.97)

31.16

(31.90)

0.11 NA 15.22

(42.32)

0.10

Urinary incontinenceb NA 5.75

(17.97)

11.77

(16.42)

4.17

(14.95)

0.09 NA -1.39

(15.48)

0.66

Dysuriab NA 5.75

(15.61)

5.88

(17.62)

1.39

(6.80)

0.19 NA -4.17

(17.89)

0.27

Abdominal painb NA 26.44

(31.34)

1.96

(8.08)

11.11

(21.23)

0.10 NA -15.28

(31.05)

0.02

Buttock painb NA 11.49

(18.42)

7.84

(14.57)

11.11

(23.40)

1.00 NA 2.78

(23.91)

0.58

Bloatingb NA 24.14

(28.03)

5.88

(13.10)

15.28

(19.61)

0.21 NA -5.56

(32.11)

0.41

Dry mouthb NA 24.14

(30.73)

1.96

(8.08)

18.06

(19.61)

0.02 T1-T2:

p=0.067

T2-T3:

p=0.166

T1-T3:

p=0.086

-8.33

(22.52)

0.08


122

Hair lossb NA 0.00

(0.00)

19.61

(26.51)

20.83

(30.79)

0.02 T1-T2:

p=0.022

T2-T3:

p=1.000

T1-T3:

p=0.059

20.83

(30.79)

0.003

Tasteb NA 9.20

(17.59)

1.96

(8.08)

18.06

(25.97)

0.08 NA 9.72

(25.02)

0.07

Faecal incontinenceb NA -2.30

(17.66)

15.69

(33.58)

5.56

(23.40)

0.04 T1-T2:

p=0.059

T2-T3:

p=0.414

T1-T3:

p=0.783

15.28

(32.57)

0.03

Sore skinb NA 2.30

(25.09)

0.00

(16.67)

18.06

(32.57)

0.37 NA 16.67

(39.32)

0.05

Embarrassmentb NA -2.30

(19.78)

5.88

(24.25)

14.49

(35.99)

0.52 NA 15.94

(37.43)

0.05

Abbreviation: T1, Time-point 1 (baseline); T2, Time-point 2 (6 weeks after surgery); T3, Time-point 3 (6 months after surgery); ANOVA, Analysis of variance; NA,

not available; EORTC QLQ C-30, the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire; QLQ-CR29, the European

Organization for Research and Treatment of Cancer Quality of Life-colorectal cancer module; QoL, quality of life.

A Higher score indicates better functioning

b Higher score indicates higher level of symptoms



123

5.4 Discussion

To our knowledge, this is the first study assessing pelvic floor symptoms, physical

and psychological outcomes of Australian patients following surgery for CRC. Our

study showed that compared to pre-operative levels, clinically meaningful deficits

appeared with respect to stool frequency, hair loss, faecal incontinence, symptoms of

peri-anal skin soreness, and bowel embarrassment measured with HRQoL instrument

up to six months after CRC surgery. Due to the growing number of patients

undergoing CRC surgery, our results have significant clinical implications for the

supportive care and survivorship management of patients with CRC and provide

evidence to inform expectations about the course of recovery. Although overall

physical and psychological function may be recovered within 6 months following

surgery, patients still experience significant bowel symptoms for up to 6 months.

Pelvic floor muscle training has been shown to be associated with improvements in

pelvic floor dysfunction in patients following surgery for CRC (Lin, Granger, Denehy,

& Frawley, 2015) and other cancer populations with pelvic floor problems (Yang et

al., 2012). Our findings highlight the importance of the emerging field of survivorship

care in CRC and inform future research to evaluate the effects of PFM training plus or

minus pre-or post-operative general oncology rehabilitation programs in improving

recovery, bowel symptoms, and general health in patients with CRC. Oncology

rehabilitation is a growing area of physiotherapy practice and one that warrants

continued research.

In contrast to the incidence of post-operative bladder, bowel, and sexual dysfunction

observed in other studies (Nikoletti et al., 2008; Perera et al., 2008), no significant

changes were found in pelvic floor symptoms as measured by APFQ, ICIQ-B,

ICIQ-UI SF six weeks and six months after surgery in our study. This may be due to

the fact that our study included a higher percentage of patients treated for colon

cancer compared to patients with rectal cancer (ratio 2:1) and that the majority of our

participants (86.7%) did not receive CT and/or RT before surgery. It is recognized

that pelvic floor dysfunction is more prevalent and severe in patients with rectal

cancer than patients with colon cancer as the more distal tumour level and level of

anastomosis increase the risk of injury to the autonomic nerves, pelvic floor, and anal



124

sphincter (Brown, Fenech, & McLeod, 2008; Fish & Temple, 2014). Pre-and

post-operative chemoradiotherapy has also been shown to have detrimental effects on

PFM function and symptoms (Bernard et al., 2015); however, only 13% of

participants in our study received preoperative chemoradiotherapy and half of the

cohort received post-operative CT. As expected the pre-operative bladder and bowel

symptoms of our cohort were higher than that of the community population (Baessler

et al., 2009; Osuga et al., 2013). Six months after surgery, the severity of some pelvic

floor symptoms (i.e. APFQ bladder and bowel domains and ICIQ-UI SF) remained

higher than the community values. As ICIQ-B is a relatively new questionnaire, there

are no published community data; hence, a comparison of our study cohort with the

community on ICIQ-B was not possible. Future studies are required to elucidate the

effects of surgery and/or adjuvant therapy on pelvic floor symptoms to improve our

understanding of this important issue.

As evidence has shown that low HRQoL scores are a risk-factor for poor survival in

older patients with CRC (Fournier et al., 2016), HRQoL has become an important

outcome measure for clinical research in CRC. We found that most of the EROTC

QLQ-C30 functioning domains returned to pre-operative level six months

post-operatively, however scores were still lower compared with community data

(Hinz et al., 2014). Our findings are similar to previous studies (Tsunoda, Nakao,

Hiratsuka, Tsunoda, & Kusano, 2007; Wilson & Alexander, 2008). Despite the

recovery of anxiety and abdominal pain by 6 months following CRC surgery, our

study showed that participants still suffered from hair loss and several bowel

symptoms, such as stool frequency, faecal incontinence, peri-anal skin soreness and

embarrassment by bowel movements 6 months following surgery. Bailey et al.

(Bailey et al., 2015) reported similar results in a group of long-term CRC survivors.

Although a previous study has indicated that the QLQ-CR29 is a useful questionnaire

in evaluating patients with rectal cancer who have undergone curative surgery (Peng

et al., 2011), more studies are warranted to evaluate the CRC-specific HRQoL

measured using QLQ-CR29 in patients with colon cancer.

While no significant differences were found in the bowel domains of the APFQ and

ICIQ-B subscales before and after CRC surgery, statistically and clinically worse



125

faecal incontinence measured using QLQ-CR29 was found at 6 months following

surgery. Our finding is in contrast to the previous study by Chen et al. (Chen, Wiltink

et al., 2015), which found an association between bowel dysfunction, measured using

a bowel dysfunction-specific questionnaire and HRQoL measured using the EORTC

QLQ-C30 and QLQ-CR29. However, it should be noted that our results are not

directly comparable to that of Chen et al. due to the different pelvic floor symptom

questionnaires used and the higher proportion of patients with colon cancer were

included in our study. Moreover, different items of the questionnaires may also

account for the discrepancy in our findings on bowel symptoms given that the faecal

incontinence subscale in the QLQ-CR29 consists of only one question on stool

leakage; whereas, the APFQ and ICIQ-B provide a summed score of questions such

as defecation frequency, bowel consistency, faecal urgency, flatus incontinence in

additional to faecal incontinence. While the bowel function domain of APFQ may be

valid in patients with CRC as shown in Study 1 (Chapter 3), no universally accepted

questionnaire to measure CRC-specific bowel symptoms (e.g. peri-rectal bleeding and

abdominal pain) in CRC populations has been established. As bowel symptoms are

the common side-effects of CRC treatment (Fish & Temple, 2014), future studies are

required to investigate the optimal bowel-specific instrument that is valid and

applicable for patients with CRC.

In contrast to prior research which found patients with CRC reduced their

participation in strenuous-intensity PA during adjuvant therapy, and spent greater

time in mild intensity PA after treatment (Chung et al., 2013); we found no significant

changes in PA levels before and after CRC surgery. As the percentage of participants

with moderate PA levels was similar before and 6 months after surgery (31% and

32%), this suggests that participants may not have received advice or encouragement

from health care professionals to engage in regular PA following CRC surgery (Lynch,

Owen, Hawkes, & Aitken, 2010). Overall we found corresponding low levels of PA

in our cohort both before and after surgery. Physical activity is very important for

patients with CRC and is associated with improvements in physical fitness (Cramer et

al., 2013) and HRQoL (Otto et al., 2015). Physical activity may also influence

survival and a previous meta-analysis estimated that each 10 MET-hour per week

increase in PA (equivalent to at least 150 minutes/week of moderate intensity PA)



126

after diagnosis was associated with 28% (95% CI = 11–36%) lower risk of mortality

among CRC survivors (Schmid & Leitzmann, 2014). Therefore our results suggest

patients following surgery for CRC should be either referred to physiotherapy or

exercise rehabilitation programs, or encouraged to engage in regular PA by their

treating physician (Fisher, Smith, & Wardle, 2016) as part of usual care.

This is the first study investigating pelvic floor symptoms, PA levels, psychological

outcomes and HRQoL in Australian patients who have undergone surgery for colon or

rectal cancer in a prospective study design. As mentioned previously, few studies

have evaluated pelvic floors symptoms in patients following surgery for colon cancer.

With a higher proportion of patients with colon cancer in our study, more information

is added to current literature about physical and psychological outcomes of this

patient group. There are several limitations in our study. The primary limitation of

this study is that the small sample size makes it difficult to conduct subgroup analyses

in patients with rectal cancer versus colon cancer or surgery only versus surgery plus

neo-adjuvant / adjuvant therapy. It is possible that different treatment regimens may

have an effect on patient symptoms and patterns of change in PA levels (Granger,

Parry, Edbrooke, & Denehy, 2016). Moreover, the findings of this study may not be

generalized to all CRC populations due to the possible selection bias and potential

confounders (i.e. comorbidities of patients) which were not collected. Although

participants were not referred to a continence service from the hospital, it is not

known if the participants received treatment from private clinics. Despite these

limitations, our findings inform future research to design appropriate interventions or

rehabilitation programs to treat the distressing bowel symptoms in patients post-CRC

surgery, as optimal bowel management following CRC surgery has not been

addressed in clinical pathway or guidelines (El-Shami et al., 2015).

5.5 Summary

Patients undergoing surgery for CRC experience worsened bowel symptoms

including incontinence from pre- to six months post-surgery. However, bladder and

sexual function, PA levels, and depression were unchanged. The findings of a higher

percentage of participants with persistent low PA levels and worse bowel symptoms



127

after CRC surgery compared to pre-operative levels indicate the need for healthcare

professionals to provide information about the benefits of increasing PA levels and

access to the continence service specialist for bowel management when required at

patient post-operative follow-ups. The next chapter describes a pilot non-randomized

quasi-control trial conducted in Australia, which provided a general oncology

rehabilitation program to patients following CRC surgery in attempt to address some

of these un-met patient needs.

Chapter 6. A multidisciplinary rehabilitation program for patients following surgery for

colorectal cancer

128

Chapter 6. A general oncology rehabilitation program for patients following

surgery for colorectal cancer – a pilot study

6.1 Introduction

Oncology rehabilitation is a rapidly growing area of cancer management to mitigate

the symptoms and side effects caused by cancer and its treatment. Patients with CRC

often experience impaired physical function, malnutrition and psychosocial sequelae

of cancer and cancer treatment (Daudt, Cosby, Dennis, Payeur, & Nurullah, 2012;

Medeiros et al., 2010), which are associated with poor HRQoL in patients following

CRC treatment (Gupta et al., 2006). To address the physical, psychological, and social

challenges and needs of patients after cancer treatment, many oncology rehabilitation

programs which combine physical and psychosocial interventions have been

developed and assessed in various cancer populations (Dingman et al., 2008;

Hanssens et al., 2011; Spruit, Janssen, Willemsen, Hochstenbag, & Wouters, 2006).

Guidelines by Rock et al. (2012) have also addressed cancer survivors’ concerns

regarding food choices, dietary supplements and PA (Rock et al., 2012). However, a

recent study on utilization of supportive care after primary treatment for CRC has

reported that only 4.6 % of CRC survivors participated in an oncology rehabilitation

program consisting of physical exercise and psycho-education following CRC surgery

(Holla, van de Poll-Franse, Huijgens, Mols, & Dekker, 2016) and the clinical changes

after utilization of supportive care were not measured. Therefore, the effects of a

general oncology rehabilitation program including disciplines such as physiotherapy,

exercise physiology, dietetics, and psychology on physical and psychosocial

symptoms have not yet been evaluated specifically in patients with CRC.

Physical interventions including exercise therapy are one of the most common

components of oncology rehabilitation with solid evidence for efficacy (Gudbergsson

et al., 2015). Exercise training is recommended by the American College of Sports

Medicine as safe and effective in improving physical functioning, HRQoL, and

cancer-related fatigue in cancer survivors both during and after cancer treatment

(Schmitz et al., 2010). In addition, evidence is emerging regarding the positive effect


colorectal cancer

129

of PA on cancer recurrence and survival in several tumour streams (Rock et al., 2012).

Increases in PA after CRC diagnosis are found to be associated with reduced risk of

CRC recurrence and mortality (Van Blarigan & Meyerhardt, 2015; Vrieling &

Kampman, 2010).

Current evidence for the effectiveness of exercise training specifically in CRC

survivors is emerging. A recent systematic review and meta-analysis of five RCTs

with a total of 238 patients with CRC found strong evidence for short-term

improvements of physical fitness in patients after exercise interventions compared

with controls (Cramer et al., 2013). However, the effects of exercise on HRQoL and

the long-term effects of exercise interventions were inconclusive due to the small

number of trials (Cramer et al., 2013). No well-designed trials have been published

since those included in the Cramer systematic review. Although the health care and

cancer care systems may be different across countries, the recommendations on PA

for cancer and non-cancer populations in the international guidelines are very similar

(Rock et al., 2012; World Health Organization, 2010). Therefore, the American

Cancer Society Guidelines, which recommend cancer survivors engage in regular PA

for at least 150 minutes per week and muscle strengthening activities at least 2 days

per week (Rock et al., 2012), are likely to be applicable for other countries and were

implemented in this study. As the feasibility of implementing an exercise program for

patients with CRC has not been reported, the feasibility of implementing the

American Cancer Society guidelines in the oncology rehabilitation program was the

primary aim of this study with view to implementing the program as a clinical service

for patients with CRC should the pilot study be successful.


Primary aim

Aim 1: To investigate the feasibility of implementing a general oncology

rehabilitation program for patients following surgery for CRC.


colorectal cancer

130

Hypothesis 1: The general oncology rehabilitation program will be a safe and feasible

therapy option for patients following surgery for CRC.

Secondary aims

Aim 2: To explore changes in functional exercise capacity, muscle strength,

psychological outcome, level of PA, self-efficacy, pelvic floor symptoms, and

HRQoL in patients before and after a general oncology rehabilitation program.

Hypothesis 2: Physical and psychological variables will show a trend towards

improvement following an 8-week general oncology rehabilitation program.

Aim 3: To investigate changes in psychological outcomes, level of PA, self-efficacy,

pelvic floor symptoms, and HRQoL between a ‘rehabilitation’ group and a

‘questionnaire’ only (quasi-control) group 8 weeks after the baseline assessment.

Hypothesis 3: The ‘rehabilitation’ group will show a trend towards improvement in

physical and psychological variables compared to the ‘questionnaire’ group.

6.2 Methods

This was a pilot non-randomized quasi-control study. This study is reported according

to the Transparent Reporting of Evaluations with Nonrandomized Designs (TREND)

statement (Des Jarlais, Lyles, Crepaz, & Group, 2004).

6.2.1 Participants

Inclusion/exclusion criteria

Patients were eligible if they had undergone surgery for histologically confirmed,

stage I-III CRC; had an Eastern Cooperative Oncology Group performance status of

between 0-2 (0 = fully active to 2 = up and about for 50% of a day); and had sufficient

English language skills to participate. Patients were excluded if they were aged 86 and


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over (von Gruenigen et al., 2012), were pregnant or up to 12 months postpartum, had

physical / psychiatric impairments that prevented participation in the exercise

programs, presence of other malignancies or had already been involved in a

rehabilitation program in the prior 12 months.

Recruitment and data collection

Potentially eligible patients were identified by the treating surgeons or ward / practice

nurses at Cabrini Hospital, Victoria, Australia. The surgeons provided the research

team with the patient details of interested eligible patients. An invitation letter and

summary information about the study was then posted from the surgeon’s rooms or

the research team 6 weeks after the cessation of patients’ surgical and medical

treatments. A follow-up telephone contact was made directly by the research team

approximately seven days after the study summary information had been posted, or

after the surgeon signified he had referred the patient to the study, in order to establish

if the information had been received; assess the patient’s interest and eligibility; and

make arrangements to post or email the Participant Information and Consent Form.

Once the patient had provided consent to participate, an appointment time for baseline

assessment was made. Eligible patients were recruited consecutively, and an 8-week

group-based education and exercise rehabilitation program was offered.

If patients were interested to participate in the study but declined to attend the

rehabilitation program due to distance or other factors, they were invited to complete

the postal questionnaires only and were used as a ‘quasi-control’ group in this study.

The outcome measures were obtained at baseline (time-point 1 [T1]) and immediately

post-intervention or at 8-weeks following baseline (time-point 2 [T2]). The study was

approved by the Cabrini HREC (Melbourne, Australia) (Appendix 6.1). All

participants provided signed informed consent. The protocol was registered with the

Australian and New Zealand Clinical Trial Registry (ACTRN12614000580673).


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6.2.2 Intervention

The general oncology rehabilitation program consisted of an 8-week multidisciplinary

education and exercise program. Over the 8 week program, the education components

included 1-hour nutritional advice and management provided by a dietician; 1-hour

exercise education regarding the importance of exercise to well-being, bladder and

bowel advice, and adherence to exercise provided by a physiotherapist; 3-hour action

planning for PA and implementation of exercise provided by an exercise physiologist;

and 3-hour stress management and behavioural change techniques provided by a

psychologist. The exercise component was informed by the PA guidelines for cancer

survivors by Rock et al. (Rock et al., 2012), and consisted of a moderate intensity,

combined aerobic and resistance training program jointly supervised by a

physiotherapist and exercise physiologist. The exercise program was individualised

for patients based on the results of their baseline outcome measures. The intervention

was provided twice weekly, and each session lasted approximately one hour. Verbal

cueing was provided during exercise classes to encourage PFM activation prior to an

anticipated rise in intra-abdominal pressure (the technique is called the ‘knack’)

(Miller, Ashton-Miller, & DeLancey, 1998). In addition, participants were provided

with an “Exercises for home” sheet which included instructions and photo

demonstrations for major muscle group’s resistance training to be performed at home

(Appendix 6.2). To encourage adherence to the exercise program, participants were

instructed to record the number of steps taken daily with a simple “fit bit” pedometer

(Fitbit ZipTM), plus record weekly home-based exercise to supplement the supervised

sessions, in an exercise diary (Appendix 6.3).

6.2.3 Outcomes

Socio-demographic and medical variables were recorded including age; sex; BMI;

social situation; education, employment status; marital status; level of tumour; cancer

stage; treatment type/status; length of in-patient stay after surgery; time since

operation; surgical history; and distance of home from hospital. Clinical outcomes

were evaluated by a physiotherapist who was involved in the program before and

immediately after the intervention or at 8-week follow-up (Appendix 6.4).


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Primary outcome measure

Feasibility

Feasibility measures included referral, recruitment, attendance, adherence,

withdrawals, and adverse events. Referral is the number of patients referred to the

program during the recruitment time. Recruitment rate is defined as the number of

participants consented divided by those eligible. Attendance is measured by the

number of sessions attended out of 16. Adherence was monitored through exercise

diaries completed by the participants and the reasons for not attending an exercise

session were assessed immediately after absence from a session. To be considered as

adherent to the international PA guidelines, the participants were required to do at

least 150 minutes of moderate intensity (BORG Scale ≥ 13) (Muyor, 2013) exercise

and at least two strength training sessions per week. Withdrawals during the study

period were tracked. Any adverse events were assessed and recorded by the

physiotherapist and exercise physiologist during or following intervention and

assessment (Stevinson & Fox, 2006).

Secondary outcome measures

Physical Activity

Self-reported level of PA was assessed using the short form version of the IPAQ-SF.

This is a detailed self-report questionnaire which measures frequency and duration of

several types of activity (strenuous, moderate, and mild) over the previous seven days,

and has acceptable reliability and validity (Craig et al., 2003). The total IPAQ in

MET-minutes per week is the sum of walking (3.3 MET), moderate activity (4.0

MET), and vigorous activity (8.0 MET) minutes per week (Craig et al., 2003).

Functional exercise capacity

Six-minute walk test


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Functional exercise capacity was assessed using the six-minute walk distance (ATS

Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories,

2002). As per the published American Thoracic Society guideline (ATS Committee

on Proficiency Standards for Clinical Pulmonary Function Laboratories, 2002),

participants were asked to follow standardized instructions and walk as far as possible

over a 30-meter course in 6 minutes. The distance covered in meters was documented.

The 6MWT was performed on two occasions to account for the learning effect, and

the best test result was used in analysis (Spencer et al., 2008; Wu et al., 2003). The

6WMT is a reliable measure (intraclass correlation coefficient [ICC] r = 0.93) in

patients with cancer (Schmidt et al., 2013), and reflects functional exercise required

for daily physical activities (ATS Committee on Proficiency Standards for Clinical

Pulmonary Function Laboratories, 2002).

Muscle strength

Muscle strength was assessed using handgrip dynamometry. As an indicator of

general muscle strength, hand-grip strength has been shown to be a predictor of

postoperative complications, mortality, and functional decline (Bohannon, 2001).

Hand-held dynamometry is a common, simple measurement of strength and has been

used in many patient populations including cancer (Trutschnigg et al., 2008).

Hand-grip strength was measured using the Jamar dynamometer (Lafayette

Instrument Company, USA) (Roberts et al., 2011). The participant was tested in the

position recommended by the American Society for Hand Therapists, and the best

value of the three measures was used for analysis (Peolsson et al., 2001). Hand-grip

dynamometry is a reliable instrument for assessing hand-grip strength (Mathiowetz,

2002; Roberts et al., 2011).

Psychological outcomes

Psychological outcomes were assessed with the 14-item HADS, which is composed of

an anxiety subscale and a depression subscale. Each subscale is scored from 0 to 21.


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135

As a screening instrument for emotional distress in patients with cancer (Vodermaier

& Millman, 2011), scores of 0–7 on the HADS represent a non-case of anxiety and

depression, 8–10 indicates a possible case, and 11–21 indicates a probable case

(Zigmond & Snaith, 1983). The HADS has demonstrated high internal consistency in

patient populations including cancer (Zigmond & Snaith, 1983).


Health-related quality of life was assessed by the EORTC QLQ-C30 and QLQ-CR29.

The EORTC QLQ-C30 comprises 30 items assessing functional aspects and

symptoms of HRQoL. As a supplement to EORTC QLQ-C30, QLQ-CR29 consists of

29 questions assessing the CRC-specific functional and symptom scales, such as

gastrointestinal symptoms, pain, problems with micturition, symptoms with/without

stoma, and sexual function. In the questionnaires, all scale/single item measures range

in score from 0-100. Higher scores on the functional and the global quality of life

scales represent higher level of functioning and higher HRQoL, while higher scores

on the symptom scales represent higher (worse) levels of symptomatology. The

EORTC QLQ-C30 and QLQ-CR29 have been shown to have good validity and

reliability properties (Aaronson et al., 1993; Whistance et al., 2009).

Self-efficacy

Self-efficacy for exercise and nutrition was assessed using the PES and NES

subscales of the Health-Specific Self-Efficacy Scale developed by Schwarzer R. and

Renner B (Schwarzer & Renner, 2005). Each subscale consists of 5 items, which are

scored on a 4-point Likert-type scale (1 = very uncertain, 2 = rather uncertain, 3 =

rather certain, and 4 = very certain). The total score of each subscale is the sum of the

responses to the 5 items ranging from 5-20. Higher scores indicate higher

self-efficacy. The Health-Specific Self Efficacy Scale has satisfactory psychometric

properties (Schwarzer & Renner, 2005), and is widely used in patients with chronic

diseases (Clarke, 2009).



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Pelvic floor symptoms were assessed using the APFQ (Baessler et al., 2009) and the

ICIQ-B (Cotterill et al., 2011). The APFQ is a validated, reliable, reproducible, and

sensitive to change instrument consisting of 42 questions in four domains (bladder,

bowel, pelvic organ prolapse and sexual function). The scores within each domain are

divided by the number of relevant questions and multiplied by 10; thus, the scores

range from 0-10 for each domain, giving a maximum total score of 40, and higher

scores represent worse symptoms (Baessler et al., 2009). Although the APFQ has only

been validated in female populations (Baessler et al., 2010), the questions in the

bladder and bowel domains may be applicable to males. Hence, only the bladder and

bowel domains of the APFQ were used and included in the data analysis. The ICIQ-B

was used in addition to the APFQ to obtain more comprehensive evaluation of bowel

symptoms. The ICIQ-B is a validated non-gender-specific questionnaire developed to

evaluate anal incontinence symptoms and impact on HRQoL. The ICIQ-B contains a

total of 21 questions; 17 of which are scored and arranged in 3 domains: bowel

pattern (score range 1-21), bowel control (score range 0-28), and HRQoL (score range

0-26). Four unscored items include other bowel symptoms and sexual impact. Higher

scores on the ICIQ-B represent worse bowel symptoms (Cotterill et al., 2011).

Global response change score

Participants’ self-perception of change in their overall pelvic floor symptoms and

fitness were assessed using a global rating of change scale. Global rating of change

scales are commonly used in clinical research to quantify a patient’s overall

improvement or deterioration over time (Kamper, Maher, & Mackay, 2009).

The global rating of change asks participants two single questions:

1: “How do your pelvic floor symptoms / control now, compare to your pelvic floor

symptoms / control at the start of the study?”

2: “How does your fitness now, compare to your fitness at the start of the study?”

Answers are rated on a 7-point Likert response scale (1 = Very much improved

through to 7 = Very much worse) (de Morton, Davidson, & Keating, 2010).


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6.2.4 Sample size

This was a pilot feasibility of guideline implementation study; therefore, it was not

powered to identify statistically significant changes before and after the rehabilitation

program. However, it has been recommended that a minimum of 10 participants per

group be considered for pilot feasibility studies (Hertzog, 2008; Julious, 2005). The

results of this study may assist to determine the sample size for future trials to explore

clinical efficacy and efficiency.

6.2.5 Statistical Methods

Data were analysed using the Statistical Package for Social Sciences, version 20.0 for

Windows. Descriptive statistics, such as mean and SD, and number and percentage

were used to summarize data. Data were assessed for normality using

Kolmogorov-Smirnov (Ghasemi & Zahediasl, 2012). The baseline data of the two

groups were compared using independent t-tests for continuous variables, and

chi-squared test for categorical variables. Paired-t tests were used to compare changes

in outcomes within each group before and after the oncology rehabilitation program.

Changes to each measure across time (group by time interaction) were assessed with

repeated measures analysis of covariance (ANCOVA) adjusted for any statistically

significant differences between groups on outcomes at baseline. All analyses were

tested with a significance level of p < 0.05.

6.3 Results

6.3.1 Participant flow

Figure 6.1 shows the flow of participants through the study. One-hundred and

twenty-two participants were assessed for eligibility between July 2014 and August

2015. The main reasons for ineligibility were age (age > 85) (n = 19) and advanced

cancer stage (stage IV) (n = 7). Seventy-three (59.8%) potentially eligible patients

were approached. Seventeen (23.3%) were unable to be contacted. The two main


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138

reasons for eligible patients declining to participate in the study were ‘too busy’ (n =

10) and ‘not interested’ (n = 8). Thirteen out of the 27 participants (48%) declined

specifically to participate in rehabilitation program but agreed to participate in the

postal questionnaires, hence the consent rate to the questionnaire group was 17.8% (n

= 13/73) and the consent rate to the rehabilitation program was 19.2% (n = 14/73),

giving a combined consent rate of 37% (n = 27/73). Two participants in the

rehabilitation group and three in the questionnaire group did not complete the study

(three were unable to be contacted at follow-up, one withdrew after the first session,

and one started CT before the first session) (Figure 6.1). The drop-out rate was 14.3%

for the rehabilitation group and 23.1% for the questionnaire group.


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Figure 6.1: Patient flow through the study

Total recruited (n = 27)


Not assessed for eligibility (Total =287):

o Missed (n = 180)

o On active treatment (n = 107)

Excluded (Total = 95):

1. Ineligible as assessed by surgeons (n =

49)

o Permanent stoma (n =2) o Stage IV (n = 7)

o Stage 0 (n = 5)

o Distance as barrier (n = 3) o Past inclusion date (n = 5)

o Local excision (n = 2)

o Unknown (n = 6)

o Surgeon considered patient “too old”

to undertake rehab program (n = 19)

2. Eligible but not recruited (n = 46)

o Not interested (n = 8) o Inability to read/write English (n = 2)

o Too busy/ Time demands of training

sessions (n = 10) o Transport/distance (n = 3)

o Felt “too old” to udertake rehab

program (n = 3) o Self-report already meeting exercise

guideline (n = 2)


o Too unwell (n = 1)

Consented to “questionnaire”

(n = 13)

Complete questionnaires at 2

months (T2) (n =10)

Consented to

“rehabilitation” (n = 14)

Complete assessment

post-intervention (T2) (n= 12)


n =10


n = 12

Lost to follow-up (n = 2)

o Discontinued intervention and

withdrew from study (n = 1)

o Chemotherapy started after baseline assessment (n = 1)

Lost to follow-up

(n = 3)

o Unable to

contact (n =

3)

Potentially eligible patients identified from

hospital database (n = 409)


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6.3.2 Recruitment

Eligible participants were recruited between July 2014 and August 2015 and the

follow-up period finished in October 2015.

6.3.3 Baseline Data and Baseline Equivalence

The baseline demographics and medical characteristics of the participants are

presented in Table 6-1. The mean (SD) age of the combined cohort was 70.4 ± 9.3

years, and 64% were male. Eighteen out of 22 participants (82%) had a diagnosis of

colon cancer. Fifty-five percent of the participants had undergone colectomy, and nine

(41%) participants had received adjuvant treatment (CT and RT) before and/or after

surgery (Table 6-1). There were no statistically significant differences in participant

characteristics between the rehabilitation and questionnaire groups at baseline except

the time since operation (Table 6-1).


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Table 6-1: Demographic and medical data at baseline

Variables Rehabilitation Group

n = 12 (54.5%)

Questionnaire Group

n = 10 (45.5%)

P-value

Age (mean,

SD)a

70.3 (5.6) 70.5 (12.8) 0.96

Sexb 0.23

Female 3 (25.0%) 5 (50.0%)

Male 9 (75.0%) 5 (50.0%)

BMI (mean,

SD)

26.4 (3.8) - -

Female 27.8 (3.9)

Male 25.9 (3.9)

Level of

tumourb

0.84

Colon 10 (83.3%) 8 (80.0%)

Rectum 2 (16.7%) 2 (20.0%)

Cancer stageb 0.32

I 4 (33.3%) 4 (40.0%)

II 0 (0%) 3 (30.0%)

IIA 1 (2.3%) 0 (0%)

IIB 1 (8.3%) 0 (0%)

III 3 (25.0%) 1 (10.0%)

IIIA 1 (8.3%) 0 (0%)

IIIB 2 (16.7%) 1 (10.0%)

Missing 0 (0.0%) 1 (10.0%)

Adjuvant

treatmentsb

0.30

pre-operative

chemotherapy

+ radiotherapy

2 (16.7%) 0 (0%)

post-operative

chemotherapy

4 (33.3%) 2 (20.0%)

pre-operative

chemotherapy+

radiotherapy +

post-operative

chemotherapy

1 (8.3%) 0 (0%)

no adjuvant

therapies

5 (41.7%) 7 (70.0%)

Missing 0 (0%) 1 (10.0%)

Length of

in-patient stay

(days) (mean,

SD)a

8.7 (3.0) 8.8 (5.7) 0.95

Time since

operation

(days) (mean,

SD)a

197.1 (113.1) 99.3 (73.9) 0.03


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Type of

surgeryb

0.11

right

hemicolectomy

4 (33.3%) 4 (40.0%)

left

hemicolectomy

2 (16.7%) 0 (0%)

Subtotal or

total colectomy

0 (0%) 2 (20.0%)

high anterior

resection

1 (8.3%) 3 (30.0%)

ultra-low

anterior

resection

5 (41.7%) 1 (10.0%)

Social

situationb

0.43

home alone,

independent

1 (8.3%) 2 (20.0%)

home with

family

11 (91.7%) 8 (80.0%)

Employment

statusb

0.69

working full

time

3 (25.0%) 3 (30.0%)

working part

time or as a

casual

2 (16.7%) 1 (10.0%)

retired 6 (50.0%) 5 (50.0%)

retired, home

duty

0 (0%) 1 (10.0%)

other 1 (8.3%) 0 (0%)

Marital statusb 0.42

living with

partner

1 (8.3%) 3 (30.0%)

married for

first time

7 (58.3%) 6 (60.0%)

remarried 2 (16.7%) 0 (0%)

divorced 1 (8.3%) 0 (0%)

widowed 1 (8.3%) 1 (10.0%)

Educationb 0.76

some

secondary or

high school

1 (8.3%) 2 (20.0%)

completed

secondary or

high school

0 (0%) 1 (10.0%)

some trade,

community or

TAFE college

0 (0%) 1 (10.0%)

completed

trade,

1 (8.3%) 1 (10.0%)


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community,

TAFE college

some

university

2 (16.7%) 1 (10.0%)

completed

Bachelor’s

degree

4 (33.3%) 3 (30.0%)

completed

Masters or

PhD degree

2 (16.7%) 1 (10.0%)

other 1 (8.3%) 0 (0%)

diploma 1 (8.3%) 0 (0%)

Surgical

historyb

-

bladder 1 (8.3%) 1 (10.0%)

gynaecological 2 (16.7%) 2 (20.0%)

bowel 4 (33.3%) 8 (80.0%)

anal 1 (8.3%) 0 (0%)

kidney 0 (0%) 0 (0%)

back 1 (8.3%) 0 (0%)

other 7 (58.3%) 4 (40.0%)

Distance from

Cabrinib

0.19

0 – 10km 11 (91.7%) 6 (60.0%)

10 – 20km 1 (8.3%) 3 (30.0%)

20km + 0 (0%) 1 (10.0%) Abbreviations: SD, standard deviation; n, number; %, percent; BMI, body mass index; TAFE,

Technical and further education; PhD, Doctor of Philosophy.

a Independent-t test

b Chi-square

6.3.4 Primary outcomes

Feasibility

The referral and withdrawal are detailed in 6.3.1. Seventy-three of 409 potentially

eligible patients identified from the hospital database were approached. The consent

rate to the rehabilitation group and the questionnaire group were 19.2% and 17.8%

respectively. The withdrawal rate was 14.3% for the rehabilitation group and 23.1%

for the questionnaire group. The attendance rate to the program was 95%. Reasons for

missing exercise sessions included severe hay-fever and work commitments. Seven

out of 12 participants (58.3%) completed all 16 sessions, and all (100%) participants

attended more than 85% of sessions. Two participants reported adverse events during


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the intervention period and none of the events were related to the participation in the

study (one described anal discomfort with bloody discharge on sitting and one

reported cardiac problems followed by low haemoglobin levels). These two

participants were advised to seek advice from their general practitioner and colorectal

surgeon before returning to classes. No serious adverse events attributable to the study

occurred.

Half of the participants in the rehabilitation group (6/12) completed and returned the

exercise diary after the completion of the rehabilitation program. Table 6-2 shows the

exercise adherence (exercise diary). The average daily steps collected from the Fitbit

pedometer, ranged from 8020 steps to 9788 steps (average of 8 weeks = 8773 steps)

and 50% to 83% (average of 8 weeks = 55%) of participants met the recommended

PA guidelines of 150 minutes moderate-intensity PA plus 2 strengthening sessions per

week during the intervention period.


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Table 6-2: Adherence: Exercise diary, mean (SD) or n (%)

Week Number of

steps/day,

mean (SD)

Met Cardio

Duration

Guideline

(150min/wk)

Met Cardio

Intensity Guideline

(moderate or Borg

13)

Met

Strength

Guideline

(≧ 2

sessions/wk)

Met All

Guideline

1 8282.6

(3223.5); n =

6

5/6 (83.3%) 6/6 (100%) 6/6 (100%) 5/6

(83.3%)

2 9218.3

(3915.9); n =

6

5/6 (83.3%) 5/6 (83.3%) 6/6 (100%) 4/6

(66.7%)

3 9787.8

(2832.3); n =

5

5/6 (83.3%) 5/6 (83.3%) 6/6 (100%) 4/6

(66.7%)

4 8020.2

(3034.4); n =

6

4/6 (66.7%) 5/6 (83.3%) 6/6 (100%) 3/6

(50.0%)

5 8085.2

(3376.7); n =

6

4/6 (66.7%) 5/6 (83.3%) 6/6 (100%) 3/6

(50.0%)

6 8240.2

(3462.4); n =

6

4/6 (66.7%) 5/6 (83.3%) 6/6 (100%) 3/6

(50.0%)

7 9699.9

(3442.7); n =

6

4/6 (66.7%) 5/6 (83.3%) 6/6 (100%) 3/6

(50.0%)

8 8361.9

(3825.8); n =

6

4/6 (66.7%) 5/6 (83.3%) 6/6 (100%) 3/6

(50.0%)

Overall

average

8773.4 71.4% 83.3% 100% 54.8%

6.3.5 Secondary outcomes

Change over time in the rehabilitation group

No significant differences were found in the PA levels from baseline to

post-intervention in the rehabilitation group (Table 6-3). Functional exercise capacity

was assessed in the rehabilitation group only, and the change in 6MWT distance was

not statistically significant immediately post-intervention (Table 6-3). However, the


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mean difference from baseline to post intervention (27.3 m – improvement) was

greater than the MCID of 25 meters (Gremeaux et al., 2011).

Hand-grip strength was measured in the rehabilitation group only and did not change

significantly in either males or females following the intervention (Table 6-3). The

symptoms of depression (p = 0.01), APFQ bladder domain (p = 0.03), APFQ bowel

domain (p = 0.01), ICIQ-B bowel pattern domain (p = 0.03), ICIQ-B bowel control

domain (p = 0.02), and ICIQ-B quality of life (p = 0.02) were significantly improved

following the intervention (Table 6-3). Table 6-4 shows the results of HRQoL

outcomes. Global quality of life (p = 0.02), fatigue (p = 0.01), diarrhoea (p = 0.046),

dry mouth (p = 0.04), and urinary frequency (p = 0.02) were significantly improved

following the intervention.


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Table 6-3: Outcomes: baseline to post-intervention

Variables Rehabilitation group Questionnaire group Between

group

ANCOV

A p

value**

T1

(mean,

SD)

T2

(mean,

SD)

Mean

differenc

e

(mean,

SD)

[95% CI]

Within-group

:

paired-t

p-value

T1

(mean,

SD)

T2

(mean,

SD)

Mean

differenc

e

(mean,

SD)

[95% CI]

Within-group

:

paired-t

p-value

6MWT Distance

(metres)

514.2

(78.1);

n = 12

541.4

(73.4);

n = 12

27.3

(59.0)

[-10.2 -

64.7]

0.14 - - - - -

Hand-grip

strength -

Dominant hand

(kg)

34.3

(11.0);

n = 12

34.8

(11.3);

n = 12

0.5 (3.4)

[-1.7 -

2.7]

0.62 - - - - -

Female 20.0

(4.0);

n = 3

20.7

(1.2);

n = 3

0.7 (3.1)

[-6.9 -

8.3]

0.74 - - - - -

Male 39.1

(7.8);

n = 9

39.6

(8.60);

n = 9

0.4 (3.7)

[-2.4 -

3.3]

0.73 - - - - -

APFQ Bladder

(scale: 0 － 10)a

1.4

(1.0);

n = 12

(1.3);

n = 12

-0.3 (0.4)

[-0.6 -

-0.05]

0.03 0.7

(0.6);

n = 10

1.0 (0.6);

n = 10

0.2 (0.5)

[-0.1 -

0.6]

0.15 0.009

APFQ Bowel

(scale: 0 － 10)a

2.4

(1.4);

n = 12

1.6

(0.7);

n = 12

-0.8 (0.9)

[-1.4 -

0.2]

0.01 1.5

(0.7);

n = 10

1.5 (0.6);

n = 10

0 (0.7)

[-0.5 -

0.5]

1.00 0.51

ICIQ-B Bowel

Pattern (scale: 1

－ 21)a

8.4

(4.8);

n = 12

6.1

(2.5);

n = 12

-2.3 (3.3)

[-4.4 -

-0.3]

0.03 7.1

(3.2);

n = 10

6.6 (2.5);

n = 10

-0.5 (2.0)

[-1.9 -

0.9]

0.45 0.59


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ICIQ-B Bowel

Control (scale: 0

－ 28)a

6.9

(6.7);

n = 12

4.5

(5.3);

n = 12

-2.4 (2.9)

[-4.3 -

-0.6]

0.02 2.5

(2.8);

n = 10

2.9 (2.7);

n = 10

0.4 (1.7)

[-0.8 -

1.6]

0.48 0.32

ICIQ-B Quality

of life (scale: 0

－ 26)a

7.9

(9.2);

n = 12

5.3

(7.4);

n = 12

-2.7 (3.5)

[-4.9 -

-0.4]

0.02 4.2

(6.0);

n = 10

4.3 (6.5);

n = 10

0.1 (1.8)

[-1.2 -

1.4]

0.86 0.21

IPAQ Vigorous

(MET-mins/week

)

495.3

(930.8);

n = 12

613.3

(743.5);

n = 12

118.0

(964.9)

[-495.1 -

731.1]

0.68 3128.0

(5026.7)

;

n = 10

4068.0

(6909.8) ;

n = 10

940.0

(3970.5)

[-1900.3 -

3780.3]

0.47 0.79

IPAQ Moderate

(MET-mins/week

)

370.7

(891.2);

n = 12

600.0

(503.9);

n = 12

229.3

(846.5)

[-308.5 -

767.1]

0.37 1426.7

(2237.3)

;

n = 9

1704.0

(4163.8);

n = 10

466.7

(4808.4)

[-3229.4 -

4162.7]

0.78 0.91

IPAQ Walking

(MET-mins/week

)

1208.4

(1482.8)

;

n = 12

1604.6

(2299.1)

;

n = 12

396.3

(2786.6)

[-1374.2 -

2166.8]

0.63 1184.3

(1693.7)

;

n = 9

727.8

(877.1);

n = 9

-456.5

(2100.8)

[-2071.3 -

1158.3]

0.53 0.92

IPAQ Total

(MET-mins/week

)

2074.4

(2835.2)

;

n = 12

2818.0

(2401.8)

;

n = 12

743.6

(3494.3)

[-1476.6 -

2963.8]

0.48 6006.6

(8836.3)

;

n = 9

7061.2

(10318.7)

;

n = 9

1054.6

(7828.4)

[-4962.8 -

7072.0]

0.70 0.88

HADS Anxiety

(scale: 0 － 21)a

4.3

(3.7);

n = 12

4.0

(3.6);

n = 12

-0.3 (1.4)

[-1.2 -

0.6]

0.44 4.9

(3.1);

n = 9

4.8 (4.0);

n = 9

-1.0 (2.1)

[-2.7 -

0.7]

0.21 0.45

HADS

Depression

(scale: 0 － 21)a

3.3

(2.2);

n = 12

2.0

(1.4);

n = 12

-1.3 (1.4)

[-2.2 -

-0.3]

0.01 2.2

(2.0);

n = 9

2.3 (2.1);

n = 9

0 (1.4)

[-1.2 -

1.2]

1.00 0.12

Self efficacy -

Nutrition (scale: 5

－ 20)b

16.8

(2.6);

n=12

18.1

(2.3);

n=12

1.3 (2.2)

[-0.1-2.7]

0.06 15.4

(5.6);

n = 10

15.4

(4.3);

n = 9

-1.2 (2.9)

[-3.4 -

1.0]

0.24 0.10


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Self efficacy -

Physical exercise

(scale: 5 － 20)b

16.0

(3.1);

n = 12

15.3

(2.5);

n = 12

-0.8 (3.3)

[-2.8 -

1.3]

0.44 15.3

(3.7);

n = 10

15.1

(3.6);

n = 9

-0.1 (2.7)

[-2.2 -

2.0]

0.91 0.94

Abbreviations: T1, time-point 1 (baseline); T2, time-point 2 (post-intervention or 8 weeks following baseline); ANCOVA, Analysis of covariance; ANOVA,

Analysis of variance; APFQ, Australian Pelvic Floor Questionnaire; ICIQ-B, International Consultation on Incontinence Questionnaire-Bowel Module; ICIQ-UI

SF, International Consultation on Incontinence Questionnaire Short Form Questionnaire for urinary incontinence; IPAQ, International Physical Activity

Questionnaire; MET, metabolic equivalent; HADS, Hospital Anxiety and Depression Scale; SD, standard deviation; 6MWT, six minute walk test; kg, kilograms;

min, minutes; EORTC QLQ C-30, the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire; QLQ-CR29, the European

Organization for Research and Treatment of Cancer Quality of Life-colorectal cancer module.

**Adjusted for time since operation and baseline EORTC QLQ-CR29 flatulence domain.

a Higher score indicates worse severity/symptoms

b Higher score indicates higher self-efficacy


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Table 6-4: Health-related quality of life outcomes

Variables Rehabilitation group Questionnaire group Between

group

ANCOVA

p value**

T1

(mean, SD)

T2

(mean, SD)

Mean

difference

(mean, SD)

Within-gr

oup:

paired-t

p-value

T1

(mean, SD)

T2

(mean, SD)

Mean

difference

(mean, SD)

Within-gr

oup:

paired-t

p-value

EORTC QLQ

C-30

Global QoL (scale:

0 – 100) a*

73.6 (16.6);

n=12

81.9 (11.7);

n=12

8.3 (10.1)

[1.9-14.7] 0.02 86.7 (9.0);

n=10

81.5 (23.9);

n=9

-3.7 (23.2)

[-21.6-14.2]

0.65 0.16

Physical

functioning (scale:

0 – 100) a *

81.1 (17.9);

n=12

87.2 (12.2);

n=12

6.1 (20.4)

[-6.8-19.1]

0.32 95.3 (4.5);

n=10

92.6 (9.1);

n=9

-3.0 (10.1)

[-10.7-4.8]

0.40 0.59

Role functioning

(scale: 0 – 100) a

80.6 (30.0);

n=12

83.3 (21.3);

n=12

2.8 (30.0)

[-16.3-21.8]

0.75 95.0 (8.1);

n=10

96.3 (11.1);

n=9

1.9 (15.5)

[-10.0-13.7]

0.73 0.77

Emotional

functioning (scale:

0 – 100) a

84.0 (10.9);

n=12

83.3 (12.8);

n=12

-0.7 (11.5)

[-8.0-6.6]

0.84 80.8 (17.1);

n=10

75.9 (15.8);

n=9

-3.7 (11.9)

[-12.8-5.4]

0.38 0.11

Cognitive

functioning (scale:

0 – 100) a

81.9 (16.6);

n=12

88.9 (14.8);

n=12

6.9 (19.4)

[-5.4-19.3]

0.24 86.7 (10.5);

n=10

90.7 (12.1);

n=9

3.7 (13.9)

[-7.0-14.4]

0.45 0.85

Social functioning

(scale: 0 – 100) a *

77.8 (20.5);

n=12

91.7 (13.3);

n=12

13.9 (23.4)

[-1.0-28.8]

0.06 95.0 (8.1);

n=10

98.1 (5.6);

n=9

1.9 (5.6)

[-2.4-6.1]

0.35 0.63

Fatigue (scale: 0 –

100) b *

38.9 (19.8);

n=12

21.3 (15.3);

n=12

-17.6 (19.2)

[-29.8- -5.4] 0.01 18.9 (12.9);

n=10

12.3 (8.7);

n=9

-8.6 (12.1)

[-18.0-0.7]

0.07 0.20

Nausea and

vomiting (scale: 0

– 100) b

1.4 (4.8);

n=12

1.4 (4.8);

n=12

0 (7.1)

[-4.5-4.5]

1.00 3.3 (7.0);

n=10

0 (0);

n=9

-3.7 (7.3)

[-9.4-1.9]

0.17 0.19


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Pain (scale: 0 –

100) b

9.7 (28.8);

n=12

6.9 (16.6);

n=12

-2.8 (34.0)

[-24.4-18.8]

0.78 10.0 (11.7);

n=10

7.4 (12.1);

n=9

-3.7 (18.2)

[-17.7-10.3]

0.56 0.51

Dyspnoea (scale: 0

– 100) b

19.4 (26.4);

n=12

11.1 (16.4);

n=12

-8.3 (15.1)

[-17.9-1.2]

0.08 6.7 (14.1);

n=10

7.4 (14.7);

n=9

0 (23.6)

[-18.1-18.1]

1.00 0.54

Insomnia (scale: 0

– 100) b

33.3 (31.8);

n=12

36.1 (26.4);

n=12

2.8 (26.4)

[-14.0-19.6]

0.72 20.0 (28.1);

n=10

22.2 (23.6);

n=9

0 (28.9)

[-22.2-22.2]

1.00 0.55

Appetite loss

(scale: 0 – 100) b

2.8 (9.6);

n=12

0 (0);

n=12

-2.8 (9.6)

[-8.9-3.3]

0.34 6.7 (21.1);

n=10

0 (0);

n=12

-7.4 (22.2)

[-24.5-9.7]

0.35 0.71

Constipation

(scale: 0 – 100) b

2.8 (9.6);

n=12

5.6 (13.0);

n=12

2.8 (9.6)

[-3.3-8.9]

0.34 16.7 (23.6);

n=10

3.7 (11.1);

n=9

-11.1 (16.7)

[-23.9-1.7]

0.08 0.09

Diarrhoea (scale: 0

– 100) b

25.0 (32.2);

n=12

5.6 (19.2);

n=12

-19.4 (30.0)

[-38.5- -0.4] 0.046 23.3 (16.1);

n=10

11.1 (16.7);

n=9

-11.1 (16.7)

[-23.9-1.7]

0.08 0.92

Financial

difficulties (scale:

0 – 100) b

11.1 (21.7);

n=12

8.3 (15.1);

n=12

-2.8 (9.6)

[-8.9-3.3]

0.34 6.7 (14.1);

n=10

7.4 (14.7);

n=9

0 (16.7)

[-12.8-12.8]

1.00 0.57

QLQ-CR29

Body Image (scale:

0 – 100) a

86.1 (10.7);

n=12

85.2 (11.9);

n=12

-0.93 (10.0)

[-7.3-5.4]

0.75 87.8 (11.0);

n=10

92.6 (14.7);

n=9

3.7 (12.4)

[-5.8-13.3]

0.40 0.81

Anxiety (scale: 0 –

100) a

72.2(19.2);

n=12

75.0 (20.7);

n=12

2.8 (17.2)

[-8.1-13.7]

0.59 66.7 (22.2);

n=10

63.0 (20.0);

n=9

-3.7 (26.1)

[-23.7-16.3]

0.68 0.52

Weight (scale: 0 –

100) a

69.4 (30.0);

n=12

72.2 (19.2);

n=12

2.8 (33.2)

[-18.3-23.9]

0.78 66.7 (27.2);

n=10

77.8 (33.3);

n=9

11.1 (28.9)

[-11.1-33.3]

0.28 0.81

Urinary frequency

(scale: 0 – 100) b

40.3 (24.1);

n=12

22.2(25.0);

n=12

-18.1 (23.0)

[-32.7- -3.5] 0.02 25.0 (19.6);

n=10

25.9 (20.6);

n=9

- - 0.048

Blood and mucus

in stool (scale: 0 –

100) b

1.4 (4.8);

n=12

4.2 (10.4);

n=12

2.8(6.5)

[-1.3-6.9]

0.17 3.3 (10.5);

n=10

5.6 (11.8);

n=9

1.9 (5.6)

[-2.4-6.1]

0.35 0.49

Stool frequency

(scale: 0 – 100) b

33.3(29.3);

n=12

30.6(21.1);

n=12

-2.8 (34.0)

[-24.4-18.8]

0.78 11.7 (34.3);

n=10

14.8 (30.6);

n=9

7.4 (38.3)

[-22.0-36.8]

0.58 0.38

Urinary 5.6(13.0); 11.1 (21.7); 5.6 (13.0) 0.17 6.7 (14.1); 3.7 (11.1); -3.7 (11.1) 0.35 0.09


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incontinence

(scale: 0 – 100) b

n=12 n=12 [-2.7-13.8] n=10 n=9 [-12.2-4.8]

Dysuria (scale: 0 –

100) b

0 (0);

n=12

0 (0);

n=12

0 (0)

- 0 (0);

n=10

3.7 (11.1);

n=9

3.7 (11.1)

[-4.8-12.2]

0.35 0.02

Abdominal pain

(scale: 0 – 100) b *

0 (0);

n=12

0 (0);

n=12

0 (0)

- 13.3 (17.2);

n=10

7.4 (14.7);

n=9

-7.4 (27.8)

[-28.8-13.9]

0.45 0.60

Buttock pain

(scale: 0 – 100) b

8.3 (20.7);

n=12

11.1 (16.4);

n=12

2.8 (26.4)

[-14.0-19.6]

0.72 6.7 (14.1);

n=10

3.7 (11.1);

n=9

-3.7 (20.0)

[-19.1-11.7]

0.59 0.78

Bloating (scale: 0 –

100) b

19.4 (22.3);

n=12

8.3 (15.1);

n=12

-11.1 (29.6)

[-29.9-7.7]

0.22 13.3 (17.2);

n=10

14.8 (17.6);

n=9

0 (16.7)

[-12.8-12.8]

1 0.28

Dry mouth (scale:

0 – 100) b

16.7 (22.5);

n=12

5.6 (13.0);

n=12

-11.1 (16.4)

[-21.5- -0.7] 0.04 3.3 (10.5);

n=10

7.4 (14.7);

n=9

7.4 (14.7)

[-3.9-18.7]

0.17 0.10

Hair loss (scale: 0

– 100) b

13.9(17.2);

n=12

8.3 (15.1);

n=12

-5.6 (19.2)

[-17.8-6.7]

0.34 3.3 (10.5);

n=10

3.7 (11.1);

n=9

0 (16.7)

[-12.8-12.8]

1 0.38

Taste (scale: 0 –

100) b

8.3 (15.1);

n=12

5.6 (13.0);

n=12

-2.8 (17.2)

[-13.7-8.1]

0.59 3.3 (10.5);

n=10

3.7 (11.1);

n=9

0 (16.7)

[-12.8-12.8]

1 0.79

Flatulence (scale: 0

– 100) b *

38.9 (23.9);

n=12

30.6 (26.4);

n=12

-8.3 (20.7)

[-21.5-4.8]

0.19 3.3 (29.2);

n=10

14.8 (33.8);

n=9

14.8 (37.7)

[-14.1-43.8]

0.27 0.87

Faecal

incontinence

(scale: 0 – 100) b

13.9 (22.3);

n=12

11.1 (16.4);

n=12

-2.8 (17.2)

[-13.7-8.1]

0.59 -10.0

(16.1);

n=10

0 (23.6);

n=9

11.1 (28.9)

[-11.1-33.3]

0.28 0.96

Sore skin (scale: 0

– 100) b

25.0(35.2);

n=12

19.4 (30.0);

n=12

-5.6 (23.9)

[-20.8-9.6]

0.44 -6.7 (21.1);

n=10

-3.7 (20.0);

n=9

3.7 (26.1)

[-16.3-23.7]

0.68 0.40

Embarrassment

(scale: 0 – 100) b

11.1 (21.7);

n=12

5.6(13.0);

n=12

-5.6 (23.9)

[-20.8-9.6]

0.44 -10 (16.1);

n=10

3.7 (30.9);

n=9

14.8 (37.7)

[-14.1-43.8]

0.27 0.85

Impotence (scale:

0 – 100) b

25.0 (49.5);

n=12

22.2 (47.8);

n=12

-2. 8 (26.4)

[-19.6-14.0]

0.72 -3.3 (42.9);

n=10

-8.3 (46.3);

n=8

-8.3 (23.6)

[-28.0-11.4]

0.35 0.48

Dyspareunia

(scale: 0 – 100) b

-27.3

(20.1);

n=11

-33.3 (0);

n=11

-6.1 (20.1)

[-19.6-7.4]

0.34 -23.3

(22.5);

n=9

-14.8

(24.2);

n=9

7.4 (22.2)

[-9.7-24.5]

0.35 0.35


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153

Abbreviations: T1, time-point 1 (baseline); T2, time-point 2 (post-intervention or 8 weeks following baseline); ANCOVA, Analysis of covariance; ANOVA, Analysis of

variance; EORTC QLQ C-30, the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire; QLQ-CR29, the European

Organization for Research and Treatment of Cancer Quality of Life-colorectal cancer module; QoL, quality of life.

*p < 0.05 at baseline. Baseline EORTC QLQ-30 quality of life domain (p = 0.038), physical functioning domain (p = 0.02), social functioning

domain (p = 0.018), and fatigue domain (p = 0.013), and QLQ-CR29 abdominal pain domain (p = 0.037) and flatulence domain (p = 0.005)

**Adjusted for time since operation and baseline EORTC QLQ-CR29 flatulence domain.

a Higher score indicates better functioning

b Higher score indicates higher level of symptoms


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154

Comparison between the rehabilitation group and the questionnaire group

An ANCOVA adjusted for time since operation and baseline EORTC QLQ-CR29

flatulence domain showed significant group by time interaction in APFQ bladder

domain (p = 0.009). Global quality of life, physical functioning, social functioning,

fatigue, abdominal pain, and flatulence were significantly different (p < 0.05) between

the rehabilitation group and the questionnaire group at baseline. Significant group by

time interaction after controlling for time since operation and baseline EORTC

QLQ-CR29 flatulence was found in urinary frequency (p = 0.048) and dysuria (p =

0.02) as measured using QLQ-CR29. Table 6-5 summarizes participants’ global rate

of change at T2 compared with baseline. The proportion of participants who reported

better fitness was higher in the rehabilitation group (50%) than the questionnaire

group (10%).

Table 6-5: Global rate of change immediately post-intervention or 8 weeks following

baseline

Rehabilitation Group

n = 12

Questionnaire

Group n = 10

Global rate of change score-fitness, n

(%)

Much better 5 (41.7%) 3 (30.0%)

Better 6 (50.0%) 1 (10.0%)

A little better 1 (8.3%) 1 (10.0%)

No change 0 (0%) 4 (40.0%)

Missing 0 (0%) 1 (10.0%)

Global rate of change score-pelvic floor

symptoms, n (%)

Much better 2 (16.7%) 1 (10.0%)

Better 3 (25.0%) 2 (20.0%)

A little better 0 (0%) 1 (10.0%)

No change 7 (58.3%) 3 (30.0%)

A little worse 0 (0%) 1 (10.0%)

Missing 0 (0%) 2 (20.0%) Abbreviations: n, number; %, percent.

6.4 Discussion

This prospective pilot study aimed to investigate the feasibility of implementing a

general oncology rehabilitation program in CRC and to obtain preliminary data on


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155

patient outcomes before and after the rehabilitation program. Although the consent

rate was low (37% to the study and 19% to the rehabilitation program), the adherence

to the supervised exercise component of the rehabilitation program was excellent and

the drop-out rate was low. Additionally, significant differences were noted in bladder

symptoms including urinary frequency and dysuria between the rehabilitation group

and the questionnaire group over the 8-week intervention period. Significant

within-group improvements were also observed in bladder and bowel symptoms,

symptoms of depression, and HRQoL in the rehabilitation group, and no within-group

improvements were observed in the questionnaire group. These results demonstrate

that such an oncology rehabilitation program is potentially feasible in patients

following surgery for CRC and may improve important health outcomes.

Feasibility

Although other literature reports that rehabilitation programs are of interest to CRC

survivors (McGowan et al., 2013), recruitment was challenging in this study and

slower than anticipated; only 14 participants (19.2% of the eligible pool) were

enrolled over the 13 months recruitment period. A previous study has shown that

patients with CRC are less willing to participate in clinical research than patients with

prostate or breast cancer (Snyder et al., 2009). Symptoms related to CRC and its

treatments (e.g. fatigue), age, and mobility-related comorbidities (e.g. impaired

mobility) are some of the perceived barriers to PA in CRC reported in the literature

(Fisher et al., 2016) and may be a potential explanation for the low recruitment rate.

However, as fatigue is prevalent among cancer survivors of many tumour streams

(Kuhnt et al., 2009), future studies should determine the potential barriers to clinical

research participation among patients with CRC specifically. Despite the low

recruitment rate, the consent rate was higher in our study than in large intervention

trials in cancer survivors (11.1%) (Adams et al., 2015). Future studies should examine

the predictors of CRC patients' willingness to participate in rehabilitation program by

undertaking a barriers and enablers analysis and specific qualitative evaluation to

inform future recruitment strategies and programs which will be of interest to

potential participants.


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156

Adherence to the supervised exercise sessions was excellent, with a 95% attendance

rate and 100% of participants attended more than 85% of the rehabilitation sessions.

These findings are similar to a previous exercise intervention study in CRC survivors

that reported 90.7% adherence to a 12-week exercise intervention consisting of two

combined aerobic and resistance training sessions and one aerobic only session per

week, and 93% completed more than 80% of training sessions (Sellar et al., 2014).

The drop-out rate in our study (14.3%) was within the range of 3%-28% reported in

previous exercise or PA intervention research (Devin et al., 2015) that included

patients with CRC (Grimmett, Simon, Lawson, & Wardle, 2015). One participant in

the rehabilitation group became ineligible after the baseline assessment due to the

start of CT, giving our study a drop-out rate of 8% once the rehabilitation program

had commenced. Although the low drop-out rate and excellent adherence may be the

result of a recruitment bias, it also suggests that the program was acceptable to this

cohort.

Physical and psychological outcomes

The present study found no significant changes in the clinical outcome measures (i.e.

functional exercise capacity and muscle strength) after the oncology rehabilitation

program. Our finding on functional exercise capacity is in line with a previous study

in CRC that reported no significant change in functional exercise capacity as

measured with a cycle ergometer following 12 sessions of moderate-intensity exercise

training program, which was published after our study had commenced (Devin et al.,

2015). Moreover, participants in our study had relatively high functional exercise

capacity (514 meters) at baseline, which is comparable to that of the age-matched

community population (ranging 510-574 meters) (Tveter, Dagfinrud, Moseng, &

Holm, 2014). Therefore, the rehabilitation program may have had limited scope to

effect a significant change in functional exercise capacity, due to a ceiling effect of

the 6MWT. As previous studies in cardiac rehabilitation have shown that patients

with high baseline exercise capacity have less relative improvement in exercise

capacity than patients with low baseline exercise capacity following a rehabilitation

and exercise training program (Lavie & Milani, 1994) and that high initial fitness is

related to reduced training effect (Pierson, Miller, & Herbert, 2004), future research


colorectal cancer

157

investigating the effects of an exercise intervention in CRC should consider recruiting

participants with lower functional exercise capacity at baseline.

In addition to the relatively high baseline functional exercise capacity, participants in

the rehabilitation group also had a high average daily step count (> 8,000 steps/day),

which was comparable to the published data for community dwelling populations

(Aoyagi, Park, Watanabe, Park, & Shephard, 2009; Dwyer et al., 2015). One study

has suggested that the program exercise intensity could be set higher than that

recommended for the general population in order to improve functional exercise

capacity for physically active individuals (Azevedo et al., 2011). Although a

systematic review has demonstrated that moderate-intensity aerobic exercise is

effective in reducing fatigue and improving endurance in cancer survivors (Dennett,

Peiris, Shields, Prendergast, & Taylor, 2016), none of the studies included in that

review focused solely on patients with CRC. Devin et al. suggested that high-intensity

exercise training is more effective than current PA recommendations

(moderate-intensity exercise) in improving functional exercise capacity in CRC

survivors (Devin et al., 2015). Nevertheless, clinical improvement was observed in

the 6MWT distance in our study, which suggests that a moderate-intensity aerobic

and resistance training program may have a clinical effect on functional exercise

capacity. Although the 6MWT MCID has not yet been published specifically for

patients with CRC following a general oncology rehabilitation program, the mean

difference of the 6MWT distance (27.2 meters) was greater than the MCID of 25

meters as reported among coronary artery disease patients following cardiac

rehabilitation (Gremeaux et al., 2011).

Despite the fact that the baseline muscle strength of our study cohort (20kg in female

and 39kg in male) was lower than that of the community (26kg in female and 42kg in

male) (Leong et al., 2016), no significant change was found in dominant hand-grip

strength after intervention. Our finding is in contrast to the study by Sellar et al.,

which provided an exercise intervention with longer duration (12 weeks) and higher

frequency (3 sessions per week) and found significant improvements in upper and

lower body muscle strength (Sellar et al., 2014). Future studies should examine the


colorectal cancer

158

dose-response relationships between exercise intensity / frequency and muscle

strength.

A number of secondary outcomes in the rehabilitation group changed significantly

after the oncology rehabilitation program in the present study. Significant

improvements were observed in the APFQ bladder and bowel domains and all ICIQ-B

domains in the rehabilitation group following intervention. Significant between-group

difference was also observed in the APFQ bladder domain following intervention.

This suggests that in addition to numerous health benefits, general exercise may have

positive effects on pelvic floor symptoms in patients following surgery for CRC. The

physiotherapist and exercise physiologist who supervised the exercises sessions

provided PFM ‘cueing’ during exertional manoeuvres, which may have increased the

contractility of the PFMs and therefore improved bladder control. In addition, it has

been hypothesized that the increase in intra-abdominal pressure occurring during

general movements may lead to the co-contraction of the PFMs (Bø, 2004b). Most of

the current literature has examined the effect of targeted PFM training/exercise on

pelvic floor symptoms in non-cancer populations (Norton & Cody, 2012; Starr et al.,

2013). A recent systematic review evaluated the effects of PFM training for bowel

dysfunction in patients who have undergone surgery for CRC and found that PFM

training may improve the patient-reported measures of bowel function and the

HRQoL of CRC patients following surgery (Lin et al., 2015). Although

cross-sectional studies have reported that mild to moderate PA appeared to decrease

both the odds of having urinary and faecal incontinence in older women (Nygaard &

Shaw, 2016), the effects of general exercise on pelvic floor symptoms remains

unknown. Our exploratory findings add important information to the current literature

and provide a foundation for future studies to compare general exercise interventions

with greater statistical power to specific PFM training on detecting pelvic floor

symptom changes.

An alternative explanation for the observed improvement in the APFQ bladder

domain score could be as a result of one of the education sessions, which included a

brief description on the role of the PFMs in bladder and bowel function; this session

may have had an impact on participants’ awareness of bladder and bowel symptoms


colorectal cancer

159

and encouraged them to adhere to good bladder and bowel habits, or seek further

advice; neither of these outcomes were measured during our study. Moreover, as

participants in our study were not stratified according to the severity of pelvic floor

symptoms at baseline, future studies are required to allow subgroup analysis.

Despite the significant improvement found in bladder and bowel symptoms in the

rehabilitation group, no improvement in PA levels, symptoms of anxiety or

self-efficacy was observed; this concurs with findings from previous studies in mixed

cancer and CRC populations (Devin et al., 2015; Hanssens et al., 2011; Ligibel et al.,

2012). No differences in PA levels and self-efficacy between the rehabilitation and

questionnaire groups at T2 in our study suggest the possibility of natural recovery

over time in these domains. Moreover, some of the participants in the questionnaire

group might have been highly motivated to change exercise behaviour after surgery

and had resumed self-initiated normal daily activity and work; hence, they declined

the rehabilitation program as perhaps they believed that they were already active

enough, which has been reported in previous studies as one of the perceived barriers

to PA in patients with CRC (Appleton, Goodlad, Irvine, Poole, & Wall, 2013; Bhalla

et al., 2014; Lynch et al., 2010; Mizuno, Kakuta, Ono, Kato, & Inoue, 2007). While

anxiety did not change after the intervention, significant improvement in symptoms of

depression as assessed by the HADS was noted in the rehabilitation group. Similar

observations with regard to changes in depression but not anxiety have been made by

Midtgaard et al. who provided a 6-week supervised, group-based multimodal exercise

in cancer patients undergoing CT (Midtgaard et al., 2011). Nevertheless, the anxiety

score showed a trend towards a decrease in the rehabilitation group in our study. One

possible explanation for the discrepancy in the results between the anxiety and

depression is that the intensity of the rehabilitation program was insufficient to cause

changes in the anxiety, whereas the mechanism of effect of exercise on depression

may be due to the release of monoamine neurotransmitters (i.e. serotonin, dopamine,

and norepinephrine) and endorphins during aerobic exercise and the social support

network built during group exercise sessions (Brown et al., 2012; Makino et al., 2015;

North, McCullagh, & Tran, 1990).


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160

A previous meta-analysis reported no exercise intervention effect on HRQoL in CRC

(Cramer et al., 2013). However, we found significant changes in global quality of life,

diarrhoea, and urinary frequency following the oncology rehabilitation program, and

between-group differences for urinary frequency and dysuria. Diarrhoea and urinary

frequency improved after the oncology rehabilitation program, which is congruent

with the decreases in bladder and bowel symptoms as measured with the APFQ and

ICIQ-B. The improvement in HRQoL following the oncology rehabilitation program

may be due to the changes in bladder and bowel symptoms as a significant association

between bowel and bowel dysfunction and HRQoL following CRC surgery has been

reported (Juul et al., 2014; Vironen et al., 2006). Previous research has shown that

depression has a strong impact on the global quality of life of patients; therefore, the

change in global quality of life in our study may be attributable to the improvement in

symptoms of depression (Tsunoda et al., 2005).

This is the first study investing the feasibility of implementing a general oncology

rehabilitation program in patients following surgery for CRC. The low drop-out rate,

excellent program adherence, and patient-perceived improvement in fitness as

measured with global rating of change indicate that this rehabilitation program is

acceptable to the population. The low consent rate needs further investigation using

qualitative research in order to improve this aspect of feasibility in future research.

Nonetheless, the pilot nature (non-powered), small sample size, lack of a true control

(comparison) group, lack of adjustment for multiple testing and possible selection bias

are the strongest limitations of the study. Although participants were not randomized

to the two groups in our study, the questionnaire group functioned as a quasi-control

group given there were no significant differences in demographic and medical

characteristics except the time since operation (a covariate adjusted in this study)

between both groups. However, the between-group comparisons need to be

interpreted with caution due to the non-randomized design of the study. The results of

this study cannot be generalized for all patients with CRC, as the percentage of male

participants (75%) and patients who had a diagnosis of colon cancer (83%) are higher

than those reported in the population data (55% males and 66% colon cancer)

(Australian Institute of Health and Welfare, 2015a, 2015b). The 12 participants in the

rehabilitation group may have represented a group of highly motivated patients. It is


colorectal cancer

161

unknown whether motivation played a role in the improvements of the outcomes as

we did not measure this construct. Furthermore, it was impossible to determine

whether the improvements observed in the rehabilitation group were from the

education components, exercise components, the effect of time, or a combination. The

study is further limited by the lack of long-term follow-up data available by the time

the data analysis was carried out for this thesis. A prospective RCT is needed to

determine the long-term effect of an oncology rehabilitation program for CRC.

6.5 Summary

An oncology rehabilitation program which includes implementation of international

PA guidelines may be feasible and potentially beneficial for improving bladder

symptoms including urinary frequency and dysuria in patients who complete a

rehabilitation program. Moreover, general oncology rehabilitation may positively

impact on bladder and bowel symptoms, depression and HRQoL in patients with CRC.

Despite the limitations (small sample size, pilot nature, lack of a true control group

[selection bias]), this pilot study adds valuable evidence to current literature in

oncology care and informs clinicians of the feasibility and potential clinical benefits

of general oncology rehabilitation, which could be considered as a useful component

in the standard care for patient with CRC. Fully powered RCTs are warranted to

determine the optimal exercise dosage to improve functional exercise capacity in

patients with CRC and to examine the effects of general exercise compared with PFM

training on pelvic floor outcomes in this population. The next chapter further

describes changes in pelvic floor outcomes in an opportunistic sample of volunteers

within the oncology rehabilitation program.

Chapter 7. Pelvic floor outcomes in patients who have undergone general rehabilitation following

surgery for colorectal cancer

162

Chapter 7. Pelvic floor outcomes in patients who have undergone general

oncology rehabilitation following surgery for colorectal cancer: a pilot study

This study is under review for publication:

Lin K-Y, Denehy L, Granger C.L., Frawley H.C. (2016). Pelvic floor outcomes in

patients who have undergone general rehabilitation following surgery for colorectal

cancer: a pilot study. Physiotherapy Theory and Practice. Under review. Submitted

December 2016.

Author contributions for this chapter are the following: K-YL, LD, CG and HF

conceived the idea for the paper. K-YL, LD, CG and HF contributed to research

design. K-YL and HF contributed to data acquisition. K-YL, LD, CG and HF


HF obtained project funding. K-YL wrote the first draft of the manuscript and

managed manuscript submission. All authors revised the paper and provided scientific

input. All authors approved the submitted version of the manuscript.

This study was supported by grant funding (Cabrini Foundation seed funding) from

the Cabrini Institute, Cabrini Health, Victoria, Australia.

7.1 Introduction

This chapter will describe a nested study to explore changes and differences between

bladder and bowel outcomes in patients who have undergone a general oncology

rehabilitation program compared with a questionnaire-only group following surgery

for CRC. Specific PFM training has been used routinely for treatment of incontinence

in clinical practice (Bø & Herbert, 2013). However, there is a paucity of evidence on

changes in pelvic floor outcomes (muscle function, bladder, bowel, and sexual

dysfunction) in patients with CRC following general oncology rehabilitation which

does not include specific PFM training. As general fitness training is considered to be

in the ‘development’ phase for treatment of pelvic floor outcomes (Bø & Herbert,

2013), the present study documents prospective changes in pelvic floor outcomes over

time in an opportunistic sample of volunteers undertaking a general oncology



163

rehabilitation program following CRC surgery. This study is reported according to the

TREND statement (Des Jarlais et al., 2004).


paper which is currently under review with the Neurourology and Urodynamics

journal.

7.1.1 Study aims

Aim 1: To explore changes and differences between bladder and bowel outcomes in

patients who have undergone a general oncology rehabilitation program compared

with a questionnaire only group following surgery for CRC

Aim 2: To investigate the correlation between different PFM clinical outcome

measures

Aim 3: To assess the association between PFM clinical outcome measures and

severity of pelvic floor symptoms


7.2.1 Participants

This study was conducted between July 2014 to February 2016 as part of a larger

prospective study evaluating the feasibility of a general oncology rehabilitation

program for patients following surgery for abdomino-pelvic cancer. In this nested

study, patients were eligible if they had undergone surgery for histologically

confirmed stage I-III CRC; had an Eastern Cooperative Oncology Group performance

status of between 0-2 (0 = fully active, 2 = up and about for 50% of a day) and

sufficient English language skills to participate. Patients were excluded if they were

aged 86 and over, were pregnant or up to 12 months postpartum, had a permanent

ostomy, had severe physical/psychiatric impairments that prevented participation in



164

the exercise programs, presence of other malignancies or had received post-operative

supervised exercise or rehabilitation similar to the program in this study in the

preceding 12 months. Participants with CRC from a non-intervention group who only

completed questionnaires in the main study were matched by gender and level of

cancer and used as a comparison control group in this study. The study was approved

by the institutional HREC (Appendix 7.1), and all participants provided written

informed consent.

7.2.2 Interventions

The general oncology rehabilitation program consisted of an 8-week multidisciplinary

education and exercise program. The education component included 1-hour of

nutritional advice and management provided by a dietician; 1-hour of exercise

education regarding the importance of exercise to well-being, bladder and bowel

advice, and adherence to exercise provided by a physiotherapist; 3-hours of action

planning for PA and implementation of exercise provided by an exercise physiologist;

and 3-hours of stress management and coping strategies provided by a psychologist.

The exercise component consisted of a moderate intensity aerobic and resistance

training program which was supervised by a physiotherapist and exercise physiologist,

and included PFM ‘cueing’ to encourage PFM activation prior to rises in

intra-abdominal pressure which may be caused by breath holding and/or straining

during strenuous exercise. The exercise program was individualised for patients based

on the results of their baseline outcome measures. The intervention was provided

twice weekly, and each session lasted approximately one hour.

7.2.3 Outcomes

All participants in the PFM measurement study were assessed for anorectal/PFM

function in addition to measures taken for participation in the pre-post study. These

included functional exercise capacity (6MWT); self-reported level of PA (IPAQ-SF);

muscle strength; psychological status; cancer specific HRQoL; global rating of

change; pelvic floor symptoms (APFQ (Baessler et al., 2009), ICIQ-B (Cotterill et al.,

2011) and ICIQ-UI SF (Reis et al., 2010)). The measurements were taken at baseline



165

(time-point 1), immediately post-rehabilitation (time-point 2), and at 6 months

following baseline (time-point 3). The bladder and bowel symptom data (i.e. APFQ

and ICIQ-B) of participants who completed only the questionnaires (collected at three

assessment time-points) were used for matched control data. Specific PFM function

measures for this nested study are described below. Data were collected by a trained

physiotherapist.

Digital rectal examination

For this measure, participants were asked to lie in the left lateral position. The

examination was performed by inserting a lubricated, gloved index finger into the

rectum to assess the resting sphincter tone and the strength of the puborectalis and

external anal sphincter (EAS) squeeze (Talley, 2008). Participants were asked to

perform three maximal contractions of external sphincter and puborectalis, and the

strongest contraction (MVC) was recorded. Squeeze pressure or MVC was scored

using the ICS scale as “absent”, “weak”, “moderate” or “strong” (Messelink et al.,

2005). If no correct contractions were obtained, the squeeze pressure was recorded as

absent. Digital rectal examination has been shown to be reliable for the assessment of

anal sphincter strength (Kaushal & Goldner, 1991).

Anorectal manometry

After DRE, anorectal pressure was measured at rest and at MVC using a Peritron

9300A manometer (Cardio-Design, Australia), which consists of an anal probe

connected to an electronic device that shows the values of contraction in cmH2O. For

anorectal manometry measurement, examination position was the same as for DRE.

Before insertion, the Peritron was zeroed. The lubricated, covered anal sensor was

then inserted until the sensor cuff rested at the anus. Participants were asked to relax

for 10 seconds during which the resting pressure (lowest value) was recorded. Then

the participants were asked to squeeze around the sensor and hold the contraction for

30 seconds. The MVC was obtained by subtracting the lowest value obtained during

the 10-second rest from the highest pressure achieved during the first 3 seconds of the

30-second squeeze. Area under curve (cmH2O-30sec) was calculated as the sum of



166

squeeze values measured in 30 seconds. The Peritron has been found to have

satisfactory correlation (r = 0.8) with standard manometry equipment (Simpson et al.,

2006).

Transperineal ultrasound

Transperineal ultrasound was performed using a GE Voluson-e System (GE Medical

System) with a 4D transducer RAB4-8RS (4-8MHz). Participants were tested in the

supine position with hips and knees flexed to 60 degrees. The lubricated,

sheath-covered transducer was placed on the perineum. A 2-dimensional image of the

pelvic floor was visualized with a field of view of 70 degrees in the sagittal plane.

Anorectal angle (in degrees) (Raizada et al., 2010), levator hiatus A-P distance (in

centimetres) (Oversand et al., 2015), and distance from anorectal angle to the

horizontal reference line (a horizontal line drawn from pubic symphysis parallel to the

transducer surface) (in centimetres) (Raizada et al., 2010) were measured at rest and

during PFM contraction (Figure 7.1). Participants were asked to perform three

repetitions of MVCs lasting 3 seconds each, with a 3-second rest in between. The best

of the three measures (the one with the most cranial displacement) was used for

analysis (Braekken et al., 2008). The difference in measurements between MVC and

rest was calculated for levator hiatus A-P distance, anorectal angle and distance from

anorectal angle to horizontal line (Volloyhaug et al., 2015). Transperineal ultrasound

has been shown to be useful and reliable in the clinical assessment of PFM function

(Thompson et al., 2005).

A standardized data collection sheet was used to record data output (Appendix 7.2).



167

Figure 7.1: Pelvic floor measures in the sagittal plane

Participants were asked to complete a 3-day bladder diary and a 7-day bowel diary

(Abrams et al., 2010). The times of micturition and voided volumes, leakage episodes,

fluid intake, and degree of urgency were documented using the bladder diary. A

bowel diary was used to record bowel movements with the time of day, stool

consistency using the Bristol Stool Form Scale (O'Donnell et al., 1990), time spent at

toilet, presence of straining, soiling episodes, pad usage and use of medications to

assist with bowel movements.

7.2.4 Statistical Methods

Data were analysed using the Statistical Package for Social Sciences, version 20.0 for

Windows. Descriptive statistics, such as mean and SD and number and percentage

were used to summarise data. Data were assessed for normality using the

Shapiro-Wilk test (Ghasemi & Zahediasl, 2012). Changes in pelvic floor symptom

scores and bladder and bowel diary variables over time in the rehabilitation group

were assessed with repeated measures ANOVA comparing different assessment

time-points. Further analyses were conducted to compare changes in bladder and

bowel symptoms over three-assessment time points between participants in the PFM

measurement study and 10 control participants matched for gender and level of

Anorectal angle

Anorectal angle to horizontal Levator hiatus A-P direction



168

tumour using repeated measures ANOVA. Spearman’s rank correlation coefficient

rho was used to evaluate the correlations between the clinical outcome variables. The

strength of the correlation was determined by the correlation coefficient values (0.00–

0.30 = negligible; 0.30–0.50 = low positive correlation; 0.50–0.70 = moderate

positive correlation; 0.70–0.90 = high positive correlation; and 0.90–1.00 = very high

positive correlation) (Zou et al., 2003). The relationships between the clinical

measures of PFM function (anorectal manometry and TPUS) and pelvic floor

symptoms were analysed using simple linear regression with the pelvic floor

symptom scores as the dependent variable, and clinical outcome parameters as the

independent variables. All analyses were tested with a significance level of p < 0.05.

The PFM clinical outcomes are presented separately for male and female due to the

anatomical sex differences in pelvic floor structures (Seike et al., 2009).

7.3 Results

7.3.1 Participant flow and recruitment

A total of 20 participants in the pre-post study were screened between July 2014 and

August 2015. Seventeen were eligible and invited to participate in the PFM nested

measurement study (Figure 7.2). Seven of seventeen declined with a reason of ‘not

interested’ (71.4%) or ‘time demands of appointment’ (28.6%). Ten patients who

participated in the rehabilitation program agreed to undertake PFM measurements.

The consent rate was 58.8% (10/17). All participants completed 6-month follow-up

assessments.



169

Figure 7.2: Flow chart of the study

Consented (n = 10)


Analyzed

Digital rectal examination (n = 9)

Anorectal manometry (n = 9)

Transperineal ultrasound (n =10)

Bladder diary (n = 7)

Bowel diary (n = 7)

Excluded (n = 10)

1. Ineligible as assessed by investigators (n

= 3)

o Not colorectal cancer (n = 3)

2. Declined (n = 7), reasons:


o Time demands of appointment (n = 2)

Completed baseline assessment (T1) (n = 10)

Complete assessment post-intervention (T2) (n = 10)

Complete assessment at 6-month follow-up (T3) (n = 10)



170

7.3.2 Baseline Data and Baseline Equivalence

Baseline Data and Baseline Equivalence

Participant demographics are shown in Table 7-1. Seven of 10 participants were

males and the mean (SD) age of the total cohort was 70.0 ± 6.2 years. Seventy percent

of participants had a diagnosis of colon cancer, and 30% had rectal cancer. All

participants had undergone surgery for CRC (50% hemicolectomy and 50% anterior

resection), and six participants had received adjuvant treatment (CT and/or RT) before

and/or after surgery. Of the 10 participants, six had prior pelvic/pelvic floor surgery

(i.e. bladder, gynaecological, bowel, and/or anal surgery). There were no significant

differences in participant characteristics or baseline bladder and bowel symptom

scores between participants in the rehabilitation group and the questionnaire group

(Table 7-1).



171

Table 7-1: Participant demographics and clinical characteristics

Variables Rehabilitation group (n=10) Questionnaire

group (n=10)

P-value

Total

(n=10)

Mean ± SD

or n (%)

Male (n=7)

Mean ± SD

or n (%)

Female

(n=3)

Mean ± SD

or n (%)

Age, yeara 70.0 ± 6.2 69.3 ± 5.6 71.7 ± 8.6 69.00 ± 12.8 0.828

BMI, kg/m2 26.3 ± 4.2 25.7 ± 4.4 27.8 ± 3.9 NA NA

Level of

tumourb

1.000

Colon 7 (70%) 6 (85.7%) 1 (33.3%) 7 (70%)

Rectum 3 (30%) 1 (14.3%) 2 (66.7%) 3 (30%)

Cancer stageb 0.112

I 3 (30%) 2 (28.6%) 1 (33.3%) 3 (30%)

IIA 1 (10%) 1 (14.3%) 0 (0%) 3 (30%)

IIB 1 (10%) 0 (0%) 1 (33.3%) 0 (0%)

IIIA 3 (30%) 3 (42.9%) 0 (0%) 2 (20%)

IIIB 2 (20%) 1 (14.3%) 1 (33.3%) 1 (10%)

Missing 0 (0%) 0 (0%) 0 (0%) 1 (10%)

Adjuvant

treatmentsb

0.264

Pre-operative

CT + RT

2 (20%) 2 (28.6%) 0 (0%) 0 (0%)

Post-operativ

e CT

3 (30%) 3 (42.9%) 0 (0%) 2 (20%)

Pre-operative

CT + RT +

post-operativ

e CT

1 (1%) 0 (0%) 1 (33.3%) 0 (0%)

No adjuvant

therapies

4 (40%) 2 (28.6%) 2 (66.7%) 7 (70%)

Missing 0 (0%) 0 (0%) 0 (0%) 1 (10%)

Length of

in-patient

stay (days)a

8.1 ± 2.9 7.9 ± 1.5 8.7 ± 5.5 8.6 ± 5.7 0.807

Time since

operation

(days)a

169.0 ± 97.1 169.3 ±

84.3

168.3 ±

145.4

126.8 ± 85.3 0.316

Type of

surgeryb

0.236

Right

hemicolecto

my

3 (30%) 2 (28.6%) 1 (33.3%) 3 (30%)

Left

hemicolecto

my

2 (20%) 2 (28.6%) 0 (0%) 0 (0%)

Subtotal or

total

0 (0%) 0 (0%) 0 (0%) 1 (10%)



172

colectomy

HAR 1 (10%) 1 (14.3%) 0 (0%) 4 (40%)

LAR 2 (20%) 1 (14.3%) 1 (33.3%) 0 (0%)

ULAR 2 (20%) 1 (14.3%) 1 (33.3%) 2 (20%)

Pelvic/pelvic

floor surgical

historyb

0.176

Bladder

surgery

0 (0%) 0 (0%) 0 (0%) 1 (10%)

Gynaecologi

cal surgery

2 (20%) 0 (0%) 2 (66.7%) 0 (0%)

Bowel

surgery

2 (20%) 1 (14.3%) 1 (33.3%) 5 (50%)

Anal surgery 1 (10%) 1 (14.3%) 0 (0%) 0 (0%)

Gynaecologi

cal + bowel

surgery

0 (0%) 0 (0%) 0 (0%) 2 (20%)

Bladder +

bowel

surgery

1 (10%) 1 (14.3%) 0 (0%) 0 (0%)

No pelvic

floor surgical

history

4 (40%) 4 (57.1%) 0 (0%) 2 (20%)

Abbreviations: SD, standard deviation; BMI, body mass index; n, number; NA, not applicable; CT,

chemotherapy; RT, radiotherapy; HAR, high anterior resection; LAR, low anterior resection; ULAR,

ultra-low anterior resection. a Independent-t test b Chi-square

7.3.3 Outcomes

Pelvic floor muscle function (n = 10)

The results of PFM clinical assessment are presented in Table 7-2, Figure 7.3 – 7.4.

PFM MVC values measured with anorectal pressure manometry increased

immediately post-rehabilitation and were sustained at 6-month follow-up, in both

males (T1 = 147.64 cmH2O; T2 = 158.51 cmH2O; T3 = 167.29 cmH2O) and females

(T1 = 21.45 cmH2O; T2 = 42.20 cmH2O; T3 = 48.48 cmH2O). In males and females,

changes in levator hiatus A-P distance (sagittal plane), anorectal angle, and distance

from anorectal angle to horizontal line between MVC and rest increased immediately

post-rehabilitation, and all, except change in female anorectal angle, declined below

baseline or post-rehabilitation values at 6-month follow-up.



173

Table 7-2: Results of pelvic floor muscle clinical assessment in rehabilitation group

PFM variables T1 T2 T3

DIGITAL ASSESSMENT

EAS (ICS Grade) [n (%)]

Male (n=7)

Weak 1 (14.3%) 1 (14.3%) 1 (14.3%)

Moderate 4 (57.1%) 5 (71.4%) 5 (71.4%)

Strong 2 (28.6%) 0 (0%) 0 (0%)

missing 0 (0%) 1 (14.3%) 1 (14.3%)

Female (n=3)

Weak 2 (66.7%) 2 (66.7%) 1 (33.3%)

Moderate 1 (33.3%) 1 (33.3%) 2 (66.7%)

Strong 0 (0%) 0 (0%) 0 (0%)

missing 0 (0%) 0 (0%) 0 (0%)

Puborectalis (ICS Grade) [n

(%)]

Male (n=7)

Weak 1 (14.3%) 1 (14.3%) 0 (0%)

Moderate 6 (85.7%) 5 (71.4%) 6 (85.7%)

Strong 0 (0%) 0 (0%) 0 (0%)

missing 0 (0%) 1 (14.3%) 1 (14.3%)

Female (n=3)

Weak 2 (66.7%) 2 (66.7%) 0 (0%)

Moderate 1 (33.3%) 1 (33.3%) 3 (100%)

Strong 0 (0%) 0 (0%) 0 (0%)

missing 0 (0%) 0 (0%) 0 (0%)

MANOMETRY

Resting pressure, cmH2O

(mean ± SD)

Male (n=5) 60.83 (14.88) 54.46 (27.00) 51.91 (6.55)

Female (n=3) 62.28 (23.39) 63.69 (13.53) 50.35 (19.92)

MVC, cmH2O (mean ± SD)

Male (n=5) 147.64

(62.48)

158.51 (61.10) 167.29 (57.08)

Female (n=3) 21.45 (3.93) 42.20 (17.95) 48.48 (19.08)

Area under curve, cmH2O

-30sec (mean ± SD)

Male (n=5) 38440.50

(6169.70)

38386.10

(10112.36)

40718.44

(6362.75)

Female (n=3) 18117.35

(4121.24)

23635.16

(1040.59)

23187.10

(10333.05)

TRANSPERINEAL

ULTRASOUND

Distance levator hiatus (sagittal

plane) A-P direction at rest, cm

(mean ± SD)

Male (n=7) 4.81 (0.81) 5.61 (0.54) 5.48 (1.23)

Female (n=3) 5.46 (0.36) 5.74 (0.48) 5.58 (0.58)



174

Distance levator hiatus (sagittal

plane) A-P direction at MVC,

cm (mean ± SD)

Male (n=7) 4.22 (0.92) 4.97 (0.81) 5.32 (1.19)

Female (n=3) 5.14 (0.35) 4.92 (0.50) 5.07 (0.33)

Change in distance levator

hiatus (sagittal plane) A-P

direction, cm (mean ± SD)

(resting value – contraction

value)

Male (n=7) 0.59 (0.53) 0.63 (0.45) 0.16 (0.74)

Female (n=3) 0.32 (0.70) 0.82 (0.61) 0.50 (0.64)

Anorectal angle at rest, degree

(mean ± SD)

Male (n=7) 121.63 (5.33) 119.62 (10.16) 120.66 (10.09)

Female (n=3) 127.29 (7.38) 134.18 (7.84) 124.36 (9.43)

Anorectal angle at MVC,

degree (mean ± SD)

Male (n=7) 122.46 (7.55) 119.49 (8.97) 122.26 (7.00)

Female (n=3) 133.20 (1.03) 127.27 (11.17) 112.28 (9.62)

Change in anorectal angle,

degree (mean ± SD) (resting

value – contraction value)

Male (n=7) -2.84 (10.44) 0.13(12.92) -1.60 (14.64)

Female (n=3) 0.98 (8.47) 6.91 (18.86) 12.07 (6.69)

Distance from anorectal angle

to horizontal, cm at rest (mean

± SD)

Male (n=7) 2.06 (1.20) 2.57 (1.18) 2.00 (0.56)

Female (n=3) 2.23 (0.31) 2.43 (0.38) 2.58 (0.90)

Distance from anorectal angle

to horizontal, cm at MVC

(mean ± SD)

Male (n=7) 2.27 (0.75) 2.54 (1.17) 2.64 (0.73)

Female (n=3) 2.09 (0.19) 2.23 (0.61) 3.11 (0.35)

Change in distance from

anorectal angle to horizontal,

cm (mean ± SD) (resting value

– contraction value)

Male (n=7) -0.21 (0.96) 0.03 (1.10) -0.63 (0.50)

Female (n=3) 0.14 (0.13) 0.20 (0.25) -0.52 (1.22) Abbreviation: EAS, external anal sphincter; ICS, International Continence Society; T1, time-point 1

(baseline); T2, time-point 2 (immediately post-rehabilitation program); T3, time-point 3 (6 months

follow-up); n, number; %, percent; PFM, pelvic floor muscle; cmH2O, centimetre of water; A-P,

anterior-posterior; SD, standard deviation; MVC, maximum voluntary contraction.



175

Figure 7.3: Change in raw scores of anorectal manometry variables over time for

participants with CRC

Resting pressure

0

10

20

30

40

50

60

70

80

90

100

T1 T2 T3

Time point

Resti

ng

pre

ssu

re,

cm

H2O

PFM02

PFM03

PFM04

PFM05

PFM06

PFM08

PFM09

PFM10

PFM11

MVC

0

50

100

150

200

250

300

T1 T2 T3

Time point

MV

C,

cm

H2O

PFM02

PFM03

PFM04

PFM05

PFM06

PFM08

PFM09

PFM10

PFM11

Area under curve

0

10000

20000

30000

40000

50000

60000

T1 T2 T3

Time point

Are

a u

nd

er

cu

rve,

cm

H2O

-30sec

PFM02

PFM03

PFM04

PFM05

PFM06

PFM08

PFM09

PFM10

PFM11



176

Distance levator hiatus (sagittal plane) A-P direction at rest

0.0

1.0

2.0

3.0

4.0

5.0

6.0

7.0

8.0

T1 T2 T3

Time point

Dis

tan

ce l

evato

r h

iatu

s (

sag

itta

l p

lan

e)

A-

P d

irecti

on

at

rest,

cm

PFM01

PFM02

PFM03

PFM04

PFM05

PFM06

PFM08

PFM09

PFM10

PFM11

Distance levator hiatus (sagittal plane) A-P direction at MVC

0.0

1.0

2.0

3.0

4.0

5.0

6.0

7.0

T1 T2 T3

Time point

Dis

tan

ce l

evato

r h

iatu

s (

sag

itta

l p

lan

e)

A-

P d

irecti

on

at

MV

C,

cm

PFM01

PFM02

PFM03

PFM04

PFM05

PFM06

PFM08

PFM09

PFM10

PFM11

Change in distance levator hiatus (sagittal plane) A-P direction

-1.50

-1.00

-0.50

0.00

0.50

1.00

1.50

2.00

T1 T2 T3

Time point

Ch

an

ge i

n d

ista

nce l

evato

r h

iatu

s

(sag

itta

l p

lan

e)

A-P

dir

ecti

on

, cm

PFM01

PFM02

PFM03

PFM04

PFM05

PFM06

PFM08

PFM09

PFM10

PFM11



177

Anorectal angle at rest

0.0

20.0

40.0

60.0

80.0

100.0

120.0

140.0

160.0

T1 T2 T3

Time point

An

ore

cta

l an

gle

at

rest,

deg

ree PFM01

PFM02

PFM03

PFM04

PFM05

PFM06

PFM08

PFM09

PFM10

PFM11

Anorectal angle at MVC

0.0

20.0

40.0

60.0

80.0

100.0

120.0

140.0

160.0

T1 T2 T3

Time point

An

ore

cta

l an

gle

at

MV

C,

deg

ree PFM01

PFM02

PFM03

PFM04

PFM05

PFM06

PFM08

PFM09

PFM10

PFM11

Change in anorectal angle

-30.00

-20.00

-10.00

0.00

10.00

20.00

30.00

40.00

T1 T2 T3

Time point

Ch

an

ge i

n a

no

recta

l an

gle

, d

eg

ree PFM01

PFM02

PFM03

PFM04

PFM05

PFM06

PFM08

PFM09

PFM10

PFM11



178

Figure 7.4: Change in raw scores of ultrasound variables over time for participants

with CRC.

Distance anorectal angle to horizontal at rest

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

T1 T2 T3

Time point

Dis

tan

ce a

no

recta

l an

gle

to

ho

rizo

nta

l,

cm

at

rest

PFM01

PFM02

PFM03

PFM04

PFM05

PFM06

PFM08

PFM09

PFM10

PFM11

Distance anorectal angle to horizontal at MVC

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

T1 T2 T3

Time point

Dis

tan

ce a

no

recta

l an

gle

to

ho

rizo

nta

l,

cm

at

MV

C

PFM01

PFM02

PFM03

PFM04

PFM05

PFM06

PFM08

PFM09

PFM10

PFM11

Change in distance anorectal angle to horizontal

-2.50

-2.00

-1.50

-1.00

-0.50

0.00

0.50

1.00

1.50

2.00

2.50

T1 T2 T3

Time point

Ch

an

ge i

n d

ista

nce a

no

recta

l an

gle

to

ho

rizo

nta

l, c

m

PFM01

PFM02

PFM03

PFM04

PFM05

PFM06

PFM08

PFM09

PFM10

PFM11



179

Pelvic floor symptoms and signs (n = 10)

In the total cohort (male and female combined) of the rehabilitation group, there was a

statistically significant effect of time on mean APFQ bowel domain score, F (2,18) =

3.97, p = 0.037. Similarly, improvements noted in ICIQ-B bowel control domain

following rehabilitation were sustained at 6-month follow-up (p = 0.026) (Table 7-3

and Figure 7.5). No significant changes were observed in relation to the objective

measures of pelvic floor symptoms from bladder and bowel diaries except the average

24-hour voided volume, which increased significantly immediately post-rehabilitation

and was maintained at 6-month follow-up (p = 0.024) in the total cohort (Table 7-4

and Table 7-5).

APFQ bladder domain

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

T1 T2 T3

Time point

AP

FQ

bla

dd

er

do

main

sco

re

PFM01

PFM02

PFM03

PFM04

PFM05

PFM06

PFM08

PFM09

PFM10

PFM11

APFQ bowel domain

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

T1 T2 T3

Time point

AP

FQ

bo

wel

do

main

sco

re

PFM01

PFM02

PFM03

PFM04

PFM05

PFM06

PFM08

PFM09

PFM10

PFM11



180

Figure 7.5: Change in raw scores of bladder and bowel symptoms over time for

participants with CRC.

ICIQ-B bowel pattern

0.0

2.0

4.0

6.0

8.0

10.0

12.0

14.0

16.0

18.0

20.0

T1 T2 T3

Time point

ICIQ

-B b

ow

el

patt

ern

sco

re

PFM01

PFM02

PFM03

PFM04

PFM05

PFM06

PFM08

PFM09

PFM10

PFM11

ICIQ-B bowel control

0.0

2.0

4.0

6.0

8.0

10.0

12.0

14.0

16.0

18.0

20.0

T1 T2 T3

Time point

ICIQ

-B b

ow

el

co

ntr

ol

sco

re

PFM01

PFM02

PFM03

PFM04

PFM05

PFM06

PFM08

PFM09

PFM10

PFM11

ICIQ-B quality of life

0.0

5.0

10.0

15.0

20.0

25.0

T1 T2 T3

Time point

ICIQ

-B q

uali

ty o

f li

fe s

co

re

PFM01

PFM02

PFM03

PFM04

PFM05

PFM06

PFM08

PFM09

PFM10

PFM11

Chapter 7. Pelvic floor outcomes in patients who have undergone general rehabilitation following surgery for colorectal cancer

181

Table 7-3: Pelvic floor symptom scores

n Rehabilitation group Questionnaire group Between-

group p

value T1

(mean ±

SD)

T2

(mean ±

SD)

T3

(mean ±

SD)

Repeated

Measure

ANOVA

p-value

T1

(mean ±

SD)

T2

(mean ±

SD)

T3

(mean ±

SD)

Repeated

Measure

ANOVA

p-value

APFQ Bladder (scale: 0 – 10)a

Total 10 1.36

(1.13)

1.09 (1.38) 1.02 (1.11) 0.477 0.71

(0.59)

0.92

(0.59)

0.83

(0.44)

0.728 0.410

Male 7 1.30

(1.16)

0.92 (1.19) 0.86 (0.76) 0.469 0.64

(0.55)

0.98

(0.75)

0.61

(0.38)

0.720

Female 3 1.48

(1.26)

1.48 (1.99) 1.41 (1.86) - 0.89

(0.77)

0.82

(0.26)

1.11

(0.38)

-

APFQ Bowel (scale: 0 – 10)a

Total 10 2.27

(1.49)

1.50 (0.78) 1.94 (1.29) 0.037 1.77

(0.89)

1.47

(0.61)

1.47

(0.42)

0.621 0.330

Male 7 2.10

(1.55)

1.35 (0.90) 1.64 (1.34) 0.055 1.68

(1.04)

1.12

(0.44)

1.25

(0.37)

0.595

Female 3 2.65

(1.56)

1.86 (0.17) 2.65 (1.06) - 1.96

(0.45)

2.06

(0.29)

1.77

(0.29)

-

ICIQ-B Bowel Pattern (scale: 1 – 21)a

Total 10 8.20

(4.77)

6.30

(2.71)

6.50 (2.99) 0.075 7.20

(3.46)

6.13

(2.23)

6.43

(3.15)

0.663 0.467

Male 7 7.86

(3.58)

6.43 (2.82) 6.86 (3.13) 0.208 7.29

(3.86)

5.60

(1.14)

6.50

(3.70)

0.564

Female 3 9.00

(7.94)

6.00 (3.00) 5.67 (3.06) - 7.00

(3.00)

7.00

(3.61)

6.33

(3.06)

-

ICIQ-B Bowel Control (scale: 0 – 28)a


182

Total 10 7.40

(6.96)

4.90 (5.67) 4.70 (4.74) 0.026 4.00

(5.03)

2.75

(2.76)

3.14

(3.72)

0.719 0.099

Male 7 6.43

(6.75)

5.00 (6.51) 4.71 (5.02) 0.153 4.00

(5.80)

2.20

(2.77)

2.75

(4.19)

0.880

Female 3 9.67

(8.38)

4.67 (4.16) 4.67 (5.03) - 4.00

(3.61)

3.67

(3.06)

3.67

(3.79)

-

ICIQ-B Quality of Life (scale: 0 – 21)a

Total 10 8.00

(10.03)

6.20 (7.81) 5.90 (7.98) 0.213 4.00

(5.94)

4.13

(7.24)

4.57

(5.06)

0.992 0.398

Male 7 6.43

(10.03)

4.86 (7.84) 4.14 (6.49) 0.370 2.86

(3.93)

2.20

(4.38)

3.75

(5.68)

0.401

Female 3 11.67

(11.06)

9.33 (8.33) 10.00

(11.14)

- 6.67

(9.87)

7.33

(10.97)

5.67

(5.03)

-

Abbreviation: n, number of participants; T1, time-point 1 (baseline); T2, time-point 2 (immediately post-rehabilitation program); T3, time-point 3 (6 months

follow-up); ANOVA, Analysis of variance; APFQ, Australian Pelvic Floor Questionnaire; ICIQ-B, International Consultation on Incontinence Questionnaire-Bowel

Module. a Higher score indicates worse severity/symptoms



183

Table 7-4: Bladder diary results in rehabilitation group

Bladder diary variables T1 (mean ±

SD)

T2 (mean ±

SD)

T3 (mean ±

SD)

Repeated

Measure

ANOVA

p-value

Number of voids per 24hr

Total (n=7) 7.62 (2.40) 9.04 (1.42) 8.62 (0.97) 0.436

Male (n=4) 7.22 (2.68) 9.13 (1.79) 8.84 (1.10) -

Female (n=3) 8.56 (1.54) 8.89 (0.77) 8.33 (0.88) -

Frequency of diurnal voiding

per 24hr

Total (n=7) 6.12 (1.95) 7.42 (1.31) 6.86 (0.88) 0.238

Male (n=4) 5.74 (2.03) 7.40 (1.64) 6.67 (0.98) -

Female (n=3) 7.00 (1.76) 7.44 (0.77) 7.11 (0.84) -

Frequency of nocturnal

voiding per 24hr

Total (n=7) 1.50 (0.67) 1.63 (0.57) 1.76 (0.88) 0.512

Male (n=4) 1.48 (0.79) 1.73 (0.49) 2.17 (1.00) -

Female (n=3) 1.55 (0.39) 1.44 (0.77) 1.22 (0.19) -

Voided volume per 24hr, ml

Total (n=7) 1671.17

(452.71)

1973.13

(563.29)

2158.86

(674.55)

0.024

Male (n=4) 1682.86

(463.27)

1943.33

(482.66)

2192.50

(632.08)

-

Female (n=3) 1643.89

(526.12)

2022.78

(799.19)

2114.00

(872.06)

-

Volume ml of drinks per 24hr

Total (n=7) 2055.89

(734.18)

2171.46

(740.49)

2052.29

(770.41)

0.746

Male (n=4) 2203.00

(560.50)

2242.33

(679.33)

2193.59

(826.76

-

Female (n=3) 1761.67

(1084.40)

2053.34

(981.15)

1863.89

(813.70)

-

Frequency of urgency per

24hr

Total (n=7) 2.73 (2.59) 3.21 (3.12) 3.52 (3.42) 0.385

Male (n=4) 2.43 (2.50) 1.87 (2.81) 2.83 (4.26) -

Female (n=3) 3.44 (3.20) 5.44 (2.50) 4.44 (2.37) -

Leakage episodes per 24hr

Total (n=7) 0.17 (0.36) 0.25 (0.59) 0.24 (0.63) 1.000

Male (n=4) 0.10 (0.25) 0.07 (0.15) 0.00 (0.00) -

Female (n=3) 0.33 (0.58) 0.56 (0.96) 0.56 (0.96) - Abbreviation: T1, time-point 1 (baseline); T2, time-point 2 (immediately post-rehabilitation program);

T3, time-point 3 (6 months follow-up); ANOVA, Analysis of variance; ml, millilitre; SD, standard

deviation; hr, hour.



184

Table 7-5: Bowel diary results in rehabilitation group

Bowel diary

variables

T1 (mean ± SD)

T2 (mean ± SD) T3 (mean ±

SD)

Repeated

Measure

ANOVA

p-value

Number of bowel

motions per 24hr

Total (n=7) 2.70 (1.62) 2.78 (1.35) 1.90 (0.68) 0.151

Male (n=4) 2.85 (1.80) 2.65 (1.70) 1.72 (0.65) -

Female (n=3) 2.33 (1.34) 3.00 (0.67) 2.14 (0.78) -

Frequency of bowel

urgency per 24hr

Total (n=7) 0.57 (0.90) 0.59 (0.74) 0.81 (1.19) 0.283

Male (n=4) 0.53 (1.05) 0.68 (0.93) 0.68 (1.26) -

Female (n=3) 0.67 (0.58) 0.45 (0.39) 1.00 (1.32) -

Time spent at toilet

per 24hr, minutes

Total (n=7) 15.63 (13.18) 19.87 (17.80) 15.82 (8.64) 0.135

Male (n=4) 19.13 (14.41) 23.79 (21.78) 18.45 (6.86) -

Female (n=3) 7.44 (3.86) 13.33 (7.64) 12.31 (11.00) -

Frequency of

straining per 24hr

Total (n=7) 0.56 (1.10) 1.14 (1.58) 0.31 (0.40) 0.418

Male (n=4) 0.51 (1.24) 0.88 (1.74) 0.10 (0.07) -

Female (n=3) 0.67 (0.88) 1.56 (1.50) 0.58 (0.52) -

Soiling episodes per

24hr

Total (n=7) 0.28 (0.39) 0.08 (0.24) 0.48 (0.95) 0.244

Male (n=4) 0.31 (0.41) 0.13 (0.30) 0.22 (0.43) -

Female (n=3) 0.22 (0.39) 0.00 (0.00) 0.83 (1.44) -

Number of pad used

per 24hr

Total (n=7) 0.47 (1.17) 0.42 (1.18) 0.43 (0.93) 0.343

Male (n=4) 0.14 (0.38) 0.67 (1.49) 0.00 (0.00) -

Female (n=3) 1.22 (2.12) 0.00 (0.00) 1.00 (1.32) -

Frequency of use of

bowel medication per

24hr

Total (n=7) 0.17 (0.53) 0.38 (0.70) 0.14 (0.38) 0.397

Male (n=4) 0.00 (0.00) 0.27 (0.59) 0.00 (0.00) -

Female (n=3) 0.56 (0.96) 0.56 (0.96) 0.33 (0.58) - Abbreviation: T1, time-point 1 (baseline); T2, time-point 2 (immediately post-rehabilitation program);

T3, time-point 3 (6 months follow-up); ANOVA, Analysis of variance; SD, standard deviation; hr,

hour.



185

Comparison with the matched control (n = 20)

Further analyses showed no significant changes in PROMs (i.e. APFQ bladder and

bowel domains and ICIQ-B domains) between three time-points in the matched

control group (Table 7-3). However, a trend of difference was noted in ICIQ-B bowel

control between groups over time (p = 0.099).

Correlations between different PFM clinical outcome measures (n = 10)

Statistically significant moderate correlations for PFM strength were found between

MVC measured by anorectal pressure manometry and DRE measured muscle strength

of the EAS immediately post-rehabilitation (Spearman’s rho 0.73, p < 0.05). Change

in distance from anorectal angle to horizontal line between MVC and rest measured

by TPUS was also significantly and positively moderately correlated with DRE

measured muscle strength of the EAS at 6-month follow-up (Spearman’s rho 0.73, p <

0.05) (Table 7-6 , Table 7-7, and Table 7-8).



186

Table 7-6: Pelvic floor muscle strength of rehabilitation group Spearman’s correlation

at baseline (n = 9)

Spearman's rho EAS

(ICS

scale)

Puborectalis

(ICS scale)

MVC,

cmH2O

Change in

distance

levator

hiatus,

cm

Change in

anorectal

angle,

degree

Change in

distance

from

anorectal

angle to

horizontal,

cm

DIGITAL

ASSESSMENT

EAS (ICS scale) - 0.54 0.54 -0.03 -0.53 0.36

Puborectalis (ICS

scale)

- 0.55 -0.57 -0.34 -0.11

MANOMETRY

MVC, cmH2O - -0.17 -0.22 -0.43

TRANSPERINEAL

ULTRASOUND

Change in distance

levator hiatus, cm

- 0.46 0.13

Change in anorectal

angle, degree

- -0.35

Change in distance

from anorectal angle to

horizontal, cm

-

Abbreviation: EAS, external anal sphincter; ICS, International Continence Society; cmH2O, centimetre

of water; MVC, maximum voluntary contraction.



187

Table 7-7: Pelvic floor muscle strength Spearman’s correlation immediately post-

rehabilitation program (n = 9)

Spearman's rho EAS (ICS

scale)

Puborectalis

(ICS scale)

MVC,

cmH2O

Change in

distance

levator

hiatus, cm

Change in

anorectal

angle,

degree

Change in

distance

from

anorectal

angle to

horizontal,

cm

DIGITAL

ASSESSMENT

EAS (ICS scale) - 0.00 0.73* -0.32 -0.46 -0.27

Puborectalis (ICS

scale)

- 0.37 0.18 0.27 -0.27

MANOMETRY

MVC, cmH2O - -0.29 -0.30 -0.30

TRANSPERINEAL

ULTRASOUND

Change in distance

levator hiatus, cm

- 0.55 0.55

Change in anorectal

angle, degree

- -0.02

Change in distance

from anorectal angle

to horizontal, cm

-



*Correlation is significant at the 0.05 level (2-tailed).



188

Table 7-8: Pelvic floor muscle strength Spearman’s correlation at 6 months follow-up

(n = 8)

Spearman's rho EAS (ICS

scale)

MVC,

cmH2O

Change in

distance

levator

hiatus, cm

Change in

anorectal

angle,

degree

Change in

distance from

anorectal angle

to horizontal,

cm

DIGITAL

ASSESSMENT

EAS (ICS scale) - 0.13 0.10 -0.10 0.73*

MANOMETRY

MVC, cmH2O - 0.24 -0.45 -0.28

TRANSPERINEAL

ULTRASOUND

Change in distance

levator hiatus, cm

- 0.25 0.18

Change in anorectal

angle, degree

- 0.60

Change in distance

from anorectal angle to

horizontal, cm

-



*Correlation is significant at the 0.05 level (2-tailed).

Associations between PFM clinical outcome measures and pelvic floor symptoms (n

= 10)

Linear regression analysis showed that clinical outcome measures (anorectal pressure

manometry and TPUS) were not significantly associated with pelvic floor symptoms

(APFQ bladder and bowel domains and ICIQ-B) at any assessment time-point (Table

7-9).


189

Table 7-9: Linear regression analyses examining the relationship between different clinical measures of PFM function and severity of

pelvic floor symptoms

Independent

variables

Dependent variables Baseline Immediately

post-intervention

6 months follow-up

Β

(regre

ssion

coeffi

cients)

95% CI P-Valu

e

Β

(regre

ssion

coeffi

cients)

95% CI P-Valu

e

Β

(regre

ssion

coeffi

cients

)

95% CI P-Valu

e

Anorectal

manometry - MVC,

cmH2O

APFQ Bladder 0.32 -0.01-0.02 0.400 0.05 -0.02-0.02 0.892 -0.51 -0.02-0.0

1

0.199

APFQ Bowel -0.28 -0.02-0.01 0.466 -0.37 -0.01-0.01 0.322 -0.66 -0.02-0.0

01

0.073

ICIQ-B Bowel

Pattern

-0.21 -0.07-0.04 0.585 -0.34 -0.04-0.02 0.365 -0.17 -0.05-0.0

3

0.696

ICIQ-B Bowel

Control

-0.55 -0.11-0.02 0.123 -0.56 -0.10-0.01 0.114 -0.40 -0.08-0.0

3

0.327

ICIQ-B Quality of

Life

-0.49 -0.16-0.04 0.181 -0.62 -0.14-0.01 0.077 -0.50 -0.14-0.0

4

0.210

Ultrasound -

Change in distance

levator hiatus

(sagittal plane) A-P

direction, cm

APFQ Bladder -0.81 -2.31-0.69 0.246 -0.91 -3.14-1.33 0.377 -0.38 -1.65-0.8

9

0.509

APFQ Bowel -0.90 -2.94-1.14 0.340 -0.29 -1.59-1.02 0.628 0.33 -1.17-1.8

3

0.622

ICIQ-B Bowel

Pattern

-4.01 -10.15-2.1

4

0.171 2.10 -2.20-6.39 0.293 -0.23 -3.75-3.2

8

0.884

ICIQ-B Bowel -1.19 -11.28-8.9 0.793 1.92 -7.62-11.4 0.655 -0.39 -5.96-5.1 0.876


190

Control 1 6 8

ICIQ-B Quality of

Life

-6.14 -19.87-7.5

8

0.332 7.51 -4.34-19.3

5

0.182 -0.06 -9.45-9.3

3

0.989

Ultrasound -

Change in anorectal

angle, degree

APFQ Bladder -0.03 -0.12-0.06 0.456 -0.04 -0.11-0.04 0.315 0.01 -0.06-0.0

7

0.809

APFQ Bowel 0.04 -0.09-0.16 0.533 -0.01 -0.05-0.04 0.746 0.03 -0.05-0.1

0

0.419

ICIQ-B Bowel

Pattern

0.13 -0.26-0.52 0.464 0.06 -0.09-0.21 0.373 -0.01 -0.19-0.1

6

0.864

ICIQ-B Bowel

Control

0.14 -0.45-0.72 0.605 -0.06 -0.38-0.26 0.683 0.06 -0.21-0.3

3

0.615

ICIQ-B Quality of

Life

0.14 -0.70-0.99 0.704 0.04 -0.41-0.49 0.839 0.10 -0.36-0.5

6

0.624

Ultrasound -

Change in distance

anorectal angle to

horizontal, cm

APFQ Bladder -0.52 -1.58-0.55 0.294 -0.41 -1.60-0.79 0.456 0.53 -0.67-1.7

4

0.338

APFQ Bowel 0.48 -0.98-1.94 0.471 0.15 -0.53-0.84 0.619 -0.38 -1.84-1.0

9

0.568

ICIQ-B Bowel

Pattern

2.20 -2.33-6.72 0.295 0.75 -1.61-3.10 0.486 -1.26 -4.56-2.0

4

0.403

ICIQ-B Bowel

Control

4.11 -2.14-10.3

6

0.168 3.88 -0.10-7.86 0.055 -2.08 -7.29-3.1

3

0.383

ICIQ-B Quality of

Life

5.04 -4.32-14.3

9

0.249 4.65 -1.25-10.5

5

0.107 -3.90 -12.56-4.

76

0.330

Abbreviation: PFM, pelvic floor muscle; B, beta coefficient; CI, confidence interval; MVC, Maximum voluntary contraction; cmH2O, centimetre of water; A-P,

anterior-posterior; APFQ, Australian Pelvic Floor Questionnaire; ICIQ-B, International Consultation on Incontinence Questionnaire-Bowel Module.



191

7.4 Discussion

This is the first study to explore changes in PFM clinical measures and bladder and

bowel symptom outcomes in patients following a general oncology rehabilitation

program compared with a matched control group post–CRC surgery. The findings

showed significant improvements in patient-reported bowel symptoms immediately

post-rehabilitation and the improvements were maintained 6 months following

baseline. Significant correlations were found between muscle strength of the EAS

measured by DRE and MVC measured with anorectal pressure manometry, and DRE

and change in distance from anorectal angle to horizontal line between MVC and rest

measured using TPUS. No associations were found between clinical outcome

measures and patient-reported pelvic floor symptoms.

Despite the small numbers in male and female groups, our data showed maintenance

of the improvement in MVC measured by anorectal pressure manometry in males and

females immediately post-rehabilitation and at 6-month follow-up. A previous study

has shown a similar improvement in maximum squeeze pressure after a specific PFM

rehabilitation training program including electrical stimulation and biofeedback in

patients with faecal incontinence and defecation disorders following rectal cancer

surgery (Kuo et al., 2015), however we investigated changes in pelvic floor outcomes

following a general oncology rehabilitation program without specific PFM training. It

should be noted that the mean MVC value of our male cohort at baseline

(147.6cmH2O) was comparable to the MVC reading of 100-150 cmH2O reported as

normal in the Peritron Handbook (Cardio Design, 2016), while that of our female

cohort (21.45 cmH2O) was lower than the mean squeeze pressure 49 (range 7–91)

cmH2O reported by Ryhammer et al. in 75 women with no known anorectal disease

(Ryhammer, Laurberg, & Sorensen, 1997). Nevertheless, the mean MVC value of our

female cohort was closer to the mean maximum anal pressure of 24 cmH2O measured

using Peritron in patients with faecal incontinence (Simpson et al., 2006).

Furthermore, the difference in the baseline MVC values between male and female

was significant, however this accords with results from previous studies (Li, Yang,

Xu, Zhang, & Zhang, 2013; Ozgen et al., 2015). Randomized controlled trials with



192

subgroup analysis by sex are warranted to further explore the effects of general

exercise on anorectal pressure in patients following surgery for CRC.

In our study, the change in levator hiatus A-P distance and distance from anorectal

angle to horizontal line from rest to MVC increased in both males and females

post-rehabilitation. The mean values of change in levator hiatus A-P distance and

distance from anorectal angle to horizontal line from rest to MVC in females at

baseline (0.3 cm and 0.1 cm) were lower in our study compared to previous studies in

healthy women (Volloyhaug et al., 2015) and urogynaecologic patients (Albrich et al.,

2015), and the change in distance from anorectal angle to horizontal line in

nulliparous asymptomatic women (Raizada et al., 2010). The lower values in our

study may be due to the damage to the PFM structure and function caused by CRC

surgery and adjuvant therapy (Bernard et al., 2015; Hirano et al., 2011) as levator

trauma has been shown to be associated with reduced contractile function (Guzman

Rojas, Wong, Shek, & Dietz, 2014). However, there is scant knowledge on the

changes in levator hiatus and distance from anorectal angle to horizontal following

general exercise for CRC, and no strong conclusion can be drawn from our study due

to its small sample size.

Our study showed that both males and females had large anorectal angles at rest

ranging from 119.6 degree to 134.2 degree at three time-points. The widened

anorectal angle may be due to the damage to the puborectalis muscle caused by CRC

surgery (Hirano et al., 2011). Although an obtuse anorectal angle at rest suggests

weakening and increased laxity of the PFMs (Yang, Partanen, Farin, & Soimakallio,

1995), the clinical significance of the anorectal angle as an indicator of pelvic floor

dysfunction is uncertain. The normal values of anorectal angle at rest vary widely in

the literature, ranging from 60 degree to 114 degree (Pittman, Benson, & Sumners,

1990) and the findings of asymptomatic and symptomatic individuals may overlap

(Schreyer et al., 2012). Moreover, Pittman et al. have reported that patients who had

partial incontinence with an abnormally large anorectal angle were able to

compensate with normal sphincter pressures (Pittman et al., 1990). Despite the

increase in change in anorectal angle in both males and females from rest to MVC



193

post-rehabilitation, the improvements noted in PFM strength and MVC as measured

by DRE and anorectal manometry post-rehabilitation suggested a compensation by

non-injured muscle fibres of anal sphincters and puborectalis (Hilde et al., 2013).

Nevertheless, more studies are needed to further explore PFM function in the CRC

population.

As discrepancy often exists between clinicians’ assessment of patients’ outcomes and

the degree of bother perceived by patients (Avery et al., 2007), PROMs (severity of

symptoms) represent the most important clinical outcomes from a patient perspective

(Kelleher et al., 2013). Our findings of significant improvements in APFQ bowel

domain and ICIQ-B bowel control in the rehabilitation group and no changes in the

‘matched control’ group suggest that general exercise with the components we

provided, may have beneficial effects on bowel symptoms in patients following

surgery for CRC. A trend of difference in ICIQ-B bowel control was observed

between groups over time. With such a small group of participants in our study, this

finding is encouraging and supports the potential positive effect of a general exercise

program as we provided, on bowel symptoms. Nevertheless, a specific PFM training

program may provide a stronger effect, and this requires investigation.

Despite the observed improvements in bowel symptoms and MVC values measured

with anorectal manometry post-rehabilitation, no significant associations were found

between these measures. This finding concurs with that of Wasserberg et al. (2011)

who noted no correlation between squeeze pressures and bowel symptoms in a group

of patients with faecal incontinence (Wasserberg, Mazaheri, Petrone, Tulchinsky, &

Kaufman, 2011). Moreover, our finding is consistent with two previous studies, which

reported no significant relationships between subjective and clinical outcomes

following biofeedback treatment in patients with faecal incontinence (Norton,

Chelvanayagam, Wilson-Barnett, Redfern, & Kamm, 2003) and in patients with

faecal incontinence after surgery for CRC (Allgayer, Dietrich, Rohde, Koch, &

Tuschhoff, 2005). However, we acknowledge that our study was exploratory (not

powered). Further studies are required to identify the predictive values of clinical

measures on severity of bladder and bowel symptoms in patients with CRC.



194

Our study showed that MVC as measured by DRE of the EAS is significantly

correlated with MVC values measured by anorectal manometry immediately

post-rehabilitation, and with ultrasound findings at 6-months follow-up. However, the

findings should be read with caution due to the small size of our study. Moreover, our

findings are unable to be compared directly with previous studies (Dobben et al., 2007;

Favetta, Amato, Interisano, & Pescatori, 1996), due to differences in study

populations, equipment used, and study purposes. The lack of studies that have

examined relationships between DRE, anorectal pressure manometry (Peritron) and

TPUS following surgery for CRC justifies the importance of this pilot study. Despite

the exploratory nature of our study, the high correlations between DRE, anorectal

pressure manometry and TPUS suggest that DRE, which is relatively simple and

inexpensive, may be useful for the assessment of PFM strength in a CRC population

if more sophisticated equipment (i.e. anorectal manometry and ultrasound) is not

readily available in clinical practice. However, further studies are warranted to

determine the optimum measurement instrument for PFM assessment following

surgery for CRC.

There are a number of limitations to this study. As a prospective observational

pre-post pilot study, the nature of the study does not allow us to establish a causal

effect of the changes in the outcomes of interest. Another limitation was the relatively

low consent rate (58.8%), which indicates that there may have been a selection bias in

terms of the patients who agreed to be in this nested PFM measurement study. The

researcher who performed the clinical assessments was aware of participants’ medical

history; hence, information bias must be considered. However, our findings add

valuable information to the current literature as the majority of research in this field

has focused on rectal cancer only. Moreover, given the small sample of female

participants in this study, it was difficult to account for the potential confounding

factors that may have an impact on pelvic floor function and symptoms, such as

history of childbirth and hormonal status (Fish & Temple, 2014). The effects of the

cancer treatment (RT and CT) on the outcomes of interest are unknown. Participants

included in this study were not stratified according to the presence of bladder and/or

bowel symptoms prior to enrolment; hence, pre-existing symptoms may have

impacted upon the pelvic floor outcomes following the rehabilitation program.



195

Although PFM training was not provided as part of the rehabilitation program, the

program included advice on bladder and bowel habits, and verbal cueing during

exercise classes to encourage PFM activation prior to rises in intra-abdominal

pressure. Therefore it is unknown whether it was the general exercise component or

other components of the rehabilitation program which impacted on the pelvic floor

outcomes.

Despite the limitations, this is the first exploratory study investigating changes in

pelvic floor outcomes in patients with CRC who have undergone an oncology

rehabilitation program following surgery. Our findings provide a foundation for future

studies to evaluate the effects of general exercise compared with PFM training on

pelvic floor outcomes in patients with CRC.

7.5 Summary

From this exploratory analysis, patient-reported bowel symptoms improved after a

general oncology rehabilitation program in patients following surgery for CRC.

Moreover, it seems that there is a strong positive correlation between DRE and

anorectal pressure manometry following oncology rehabilitation, and DRE and TPUS

at 6-month follow-up. Further studies with larger sample sizes are needed to establish

the optimal outcome measure for pelvic floor outcomes in a CRC population. The

results of this pilot study provide useful information for future studies such as RCTs

to investigate the long-term effect of general oncology rehabilitations and or PFM

specific training programs on pelvic floor outcomes in patients with CRC. The role of

specific PFM training (as opposed to general oncology rehabilitation) in the CRC

population has been studied and the next chapter describes a systematic review of the

published studies to date.

Chapter 8. Pelvic floor muscle training for bowel dysfunction following colorectal cancer surgery: a

systematic review

196

Chapter 8. Pelvic floor muscle training for bowel dysfunction following

colorectal cancer surgery: a systematic review

This systematic review was published in 2015 (Appendix 8.1):

Lin KY, Granger C, Denehy L, Frawley H. Pelvic floor muscle training for bowel

dysfunction following colorectal cancer surgery: a systematic review. Neurourology

and Urodynamics. 2015;34(8):703-12.

Author contributions for this chapter are the following: K-YL, CG, LD and HF

conceived the idea for the paper. K-YL and CG performed the literature search and

quality assessment. K-YL wrote the first draft of the manuscript, managed manuscript

submission and subsequent reviews. All authors revised the paper and provided

scientific input. All authors approved the final version of the manuscript.

8.1 Introduction

This chapter will describe a systematic review undertaken to systematically

investigate the effect of PFM training on bowel dysfunction in patients after surgery

for CRC. Despite the publication of a previous systematic review evaluating the

conservative therapies such as pelvic floor re-education and colonic irrigation on

anorectal function in patients undergoing rectal resection for cancer and non-cancer

diagnoses (Maris, Devreese, D'Hoore, Penninckx, & Staes, 2013), this was the first

systematic review published investigating the benefit of PFM training in patients

specially with CRC. This systematic review was conducted according to the Preferred

Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

This chapter has the same content as that in the published systematic review. The new

recently published articles which were not included in the published manuscript are

briefly summarised at the end of the chapter.


systematic review

197

8.2 Review aim

To identify, evaluate and synthesize the evidence examining the effectiveness of PFM

training on bowel dysfunction in patients who have undergone CRC surgery.

8.3 Methods

No protocol for this review has been registered or published (Moher, Liberati, Tetzlaff,

& Altman, 2009).

8.3.1 Literature search

Electronic databases, MEDLINE (1950-2014), CINAHL (1982-2014), EMBASE

(1980-2014), Scopus (1823-2014), PsycINFO (1806-2014), Web of Science

(1970-2014), Cochrane Library (2014), and Physiotherapy Evidence Database

(1999-2014) were searched in March 2014 by one reviewer (K-YL) using different

combinations of the following terms: pelvic floor muscle training; rehabilitation;

physical therapy modalities; biofeedback psychology; pelvic floor exercise; kegel;

biofeedback; bowel function; defecation; faecal incontinence; gastrointestinal

function; total mesorectal excision; sphincter-saving surgery; anterior resection; APR;

colectomy; colorectal surgery; sphincter-preserving surgery; colorectal neoplasms;

rectal neoplasms; colonic neoplasms. An example of search strategy is presented in

Appendix 8.2. Electronic databases were accessed via The University of Melbourne,

Australia, with the last search run on 10 March 2014. No restrictions on the

publication date were imposed. The search was limited to articles written in English.

The reference lists of identified articles were also hand searched.

8.3.2 Selection criteria

Studies were eligible if they met the following inclusion criteria:

Types of studies


systematic review

198

Quantitative study designs including RCTs, cohort studies and case series were

eligible for inclusion. Case studies with only one participant were not eligible. Only

studies published in a peer reviewed journal were eligible.

Types of participants

Participants of any age, who had undergone surgery for colon or rectal cancer, were

eligible to be included in this review. Colorectal cancer was defined as cancer that

forms in the tissues of the colon or the rectum, and participants with any stage of CRC

were eligible (National Cancer Institute, 2014). Given the limited number of studies

available on this topic, we included studies with mixed cohorts of participants with

cancer and non-cancer diagnoses who had undergone colorectal surgery; for inclusion,

we required at least 50% of the participants in the study to have CRC, or data to be

reported separately for the cancer participants.

Types of intervention

Studies which included PFM training with or without biofeedback were eligible. This

included all types of visual, sensory, or auditory biofeedback. According to the 5th

ICI, PFM training (also known as Kegel exercise training) for treating faecal

incontinence involves the contraction of PFM including the EAS and puborectalis

(Bliss et al., 2013). For the purpose of this review, PFM training /Kegel exercise and

anal sphincter exercise will be considered together with the use of biofeedback for the

purpose of PFM strengthening (PFM training combined with anal canal pressure or

intra-anal electromyograph feedback device), sensory training (introducing a

balloon-tipped catheter into the rectum), or coordination training (employing a

pressure transducer to provide simultaneous feedback in intra-rectal and intra-anal

pressure during PFM contraction) made explicit (Bliss et al., 2013; Heymen &

Kuijpers, 2007). Studies that used solely electrical stimulation were not eligible for

inclusion.

Types of outcomes


systematic review

199

Studies were eligible for inclusion if their primary outcome was bowel function

measured by a patient-reported outcome measure (such as a bowel diary,

questionnaire, patient report) or anal manometry.

8.3.3 Screening of papers

Two reviewers (K-YL and CG) independently assessed studies based on titles and

abstracts for inclusion. Full texts of potentially relevant studies were retrieved and

reviewed by the two reviewers to evaluate the eligibility. Disagreements were able to

be resolved by a third independent reviewer (HF) although this was not required.

Authors were contacted by e-mail if more information was needed to screen an article

(this occurred on one occasion).

8.3.4 Risk of bias

As non-randomized studies were the primary study design found, the risk of bias was

assessed by the two independent reviewers using the Newcastle-Ottawa Scale (NOS)

for non-randomized studies. A third review was available if any disagreements arose

between the two reviewers (although this was not required), and a consensus

score/point was assigned after discussion. Studies were also ranked on the National

Health and Medical Research Council Hierarchy of Evidence Scale (National Health

Medical Research Council, 2009). The scoring criteria used for synthesis of bias risk

of included studies were reported as “poor” to “excellent” based on the score

calculated in the NOS.

The NOS, a valid and reliable instrument, evaluates the risk of bias of studies based

on participant selection, comparability of study groups, and the assessment of

exposure (case-control studies) or outcome (cohort studies) (Wells et al., 2005). There

are a total of eight items for both case-control studies and cohort studies. A point can

be given to each item except the items in the category of comparability in which a

maximum of 2 points can be obtained (Wells et al., 2005). A total of 7 to 9 points


systematic review

200

indicates high methodological quality (low risk of bias), a total of 4 to 6 indicates

moderate quality, and points below 4 indicate low quality (high risk of bias) (Suthar,

Granich, Mermin, & Van Rie).

8.3.5 Data extraction

An electronic data collection form was specifically developed and utilised. Data were

extracted from the included studies by one reviewer (K-YL) and crossed-checked by a

second independent reviewer (CG). Disagreements were resolved through discussion

or with the use of a third reviewer (HF). Data items extracted from the included

studies included the first author’s name; year published; number of participants;

gender; age; type of surgery; adjuvant therapy; type, duration, frequency, and length

of intervention program; and results of reviewed studies.

Statistics

Kappa statistics and percentage agreement were calculated to establish agreement

between reviewers for study selection and risk of bias using SPSS for Windows

statistical software package (SPSS Inc., Version 21, Chicago, IL) (Landis & Koch,

1977). Values of kappa greater than 0.8 reflect “excellent” agreement (Higgins &

Green, 2011). Mean and variance of pre- and post- intervention assessments were

obtained directly from the study results or calculated using the following equations

when not reported (Hozo et al., 2005; Moore, McCabe, & Craig, 2010):

Standard deviation = Range / 4

Standard deviation = Standard error of the mean (square root of the number of

samples).

8.4 Results

8.4.1 Search strategy and study selection


systematic review

201

Study selection

A total of 51 studies were identified following the electronic database search, and an

additional four studies were identified though searching reference lists. After

exclusion of duplicate records and assessment of titles and abstracts, 10 studies met

inclusion criteria and were further assessed with full text. The author of one

potentially eligible study (Chiang, Yeh, & Wang, 1997) was contacted to clarify

whether the study had included any participants with CRC; the study was

subsequently excluded because the diagnosis of participants was unknown. The study

of Hwang et al. was excluded because only three of the fourteen participants (21%) in

their study had a diagnosis of rectal cancer (Hwang et al., 2005). After assessment of

the eligibility of full-text articles, eight studies were finally included for review.

Figure 8.1 shows the flow diagram of study selection. Kappa statistics for agreement

between the two independent reviewers on title/abstracts and full text were 0.94

(percentage agreement, 98.0%) and 1.000 (percentage agreement, 100%), respectively

(Landis & Koch, 1977).


systematic review

202

Figure 8.1: PRISMA flow diagram of study selection process.

Iden

tifi

cati

on

S

creen

ing

E

lig

ibil

ity

In

clu

ded

Full-text articles assessed

for eligibility by

independent reviewers

(K-YL, CG) (n=10)

Total records (n=55)

Records after duplicate

removed and screened by

independent reviewers (KYL,

CG) (n=51)

Duplicate records (n=4)

Records excluded (n=41)

Review articles: 3

Not colorectal cancer: 1

Not PFM training/biofeedback

after surgery: 35

Conference abstract: 2

Studies included in

qualitative synthesis (n=8)

Records identified through

database searching (n=51):

MEDLINE (n=29), PEDro (n=0),

Scopus (n=4), CINAHL (n=2),

Cochrane library (n=3), EMBASE

(n=11), Web of Science (n=2), and

PsycINFO (n=0)

Additional records

identified through

reference list searching

(n=4)

Records excluded (n=2)

Not colorectal cancer: 1

< 50% participants with

colorectal cancer: 1

Studies included in

quantitative synthesis

(meta-analysis) (n=0)


systematic review

203

8.4.2 Study and participant characteristics

Study characteristics

Methods

No RCTs were found. Six prospective non-randomized studies (Bartlett, Sloots,

Nowak, & Ho, 2011; Ho, Chiang, Tan, & Low, 1996; Ho & Tan, 1997; Laforest et al.,

2012; Liu, Chen, & Lee, 2011; Pucciani, Ringressi, Redditi, Masi, & Giani, 2008) and

two retrospective review studies (Allgayer et al., 2005; Kim et al., 2011) were

included (Table 8-1).

Participants’ characteristics

The characteristics of the participants are presented in Table 8-2. A total of 374

participants were included in the studies. Six of eight studies reported data on cancer

patients only (Allgayer et al., 2005; Bartlett et al., 2011; Kim et al., 2011; Laforest et

al., 2012; Liu et al., 2011; Pucciani et al., 2008). The remaining two studies (Ho et al.,

1996; Ho & Tan, 1997) included 54% (7/13) and 91% (10/11) cancer patients,

respectively. The mean (SD) age of the participants across all studies ranged from

55.0 (11.3) to 67.0 (8.8) years. Of the eight studies, two included patients who had

undergone LAR (Allgayer et al., 2005; Ho & Tan, 1997), three following

sphincter-saving surgery (Kim et al., 2011; Laforest et al., 2012; Liu et al., 2011), and

three receiving mixed types of surgery (Bartlett et al., 2011; Ho et al., 1996; Pucciani

et al., 2008). Of the three studies with mixed types of surgery, one included patients

who had undergone colectomy for colon cancer (Bartlett et al., 2011). The majority of

studies (75%) included participants who had undergone CT and/or RT (Allgayer et al.,

2005; Ho et al., 1996; Ho & Tan, 1997; Kim et al., 2011; Laforest et al., 2012;

Pucciani et al., 2008).

Chapter 8. Pelvic floor muscle training for bowel dysfunction following colorectal cancer surgery: a systematic review

204

Table 8-1: Risk of bias in reviewed observational trials using the Newcastle-Ottawa Scale

Auth

or

and

year

Count

ry

Design NOS score

Selection (0 - 4)

Comparability

(0 - 2)

Outcome (0 - 3)

Total

(0 - 9)

NHM

RC

grade

of

evide

nce

1)

Represent

ativeness

of the

exposed

cohort

2)

Selection

of the

non

exposed

cohort

3)

Ascert

ainme

nt of

expos

ure

4)

Demonst

ration

that

outcome

of

interest

was not

present

at start of

study

1)

Comparability

of cohorts on

the basis of the

design or

analysis

1)

Assessm

ent of

outcome

2) Was

follow-

up long

enough

for

outcom

es to

occur

3)

Adeq

uacy

of

follow

up of

cohort

s

Allga

yer et

al.

2005

Germ

any

Prospect

ive case

series

* - - * * * - * 5 IV

Bartl

ett et

al.

2011

Austra

lia

Retrospe

ctive

case

series

* - - - - * - * 3 IV

Ho et

al.

1996

Singa

pore

Prospect

ive case

series

* - * * - * - * 5 IV

Ho et Singa Prospect * - * * * * - * 6 IV


205

al.

1997

pore ive case

series

Kim

et al.

2011

Korea Retrospe

ctive

case

series

* - - * - * - * 4 IV

Selection (0-4)

Comparability

(0-2)

Outcome (0-3)

1) Is the

case

definition

adequate?

2)

Represen

tativenes

s of the

cases

3)

Select

ion of

Contr

ols

4)

Definitio

n of

Controls

1)

Comparability

of cases and

controls on the

basis of the

design or

analysis

1)

Ascertai

nment of

exposure

2)

Same

method

of

ascertai

nment

for

cases

and

control

3)

Non-

Respo

nse

rate

Lafor

est et

al.

Franc

e

Prospect

ive case

control

* - * * * * - * * 7 III-2

Liu

et al.

2011

Taiwa

n

Prospect

ive

cohort

* * * * - - * - 5 III-2

Pucci

ani et

al.

2008

Italy Prospect

ive

cohort

* * - - - - * * 4 III-2

Abbreviation: NOS, Newcastle-Ottawa Scale; NHMRC, National Health and Medical Research Council, Australia.

(*) Criteria satisfied.

(-) Criteria not satisfied, high risk of bias.


206

Table 8-2: Participants in reviewed studies

Author and year Number of

participants, (n) %

Gender, M/F Mean age, year ± SD Type of surgery, (n)

%

Adjuvant

therapy, (n) %

Symptoms at

baseline

Prospective

non-randomized

trials

Allgayer et al.,

2005

95

Irradiated patients

(41) 43.2%

Non-irradiated

patients (54) 56.8%

Irradiated:

28/13

Non-irradiated:

33/21

Irradiated: 58.5 ±

11.3* (range: 31.0 -

76.0)

Non-irradiated: 67.0

± 8.8* (range:

48.0-83.0)

Low anterior

resection (95) 100%

Post-op RT

(41) 43.2%

Faecal

incontinence

Ho et al., 1996 13

10/3 62.1 ± 16.6* Anterior resection

(7) 53.8%

Total colectomy (6)

46.2%

Post-op RT

(4) 30.8%

Frequent

bowel

movement

and / episode

of

incontinence

Ho et al., 1997 11

Incontinence (6)

54.5%

Constipation (5)

45.5%

5/6 64.8 ± 10.9* Low anterior

resection (11) 100%

Post-op RT

(2) 18.2%

Incontinence

or

constipation

Laforest et al.,

2012

46

Rehabilitation

group (22) 47.8%

Control group (24)

52.2%

Rehabilitation:

11/11

Control: 15/9

Rehabilitation: 55.0 ±

11.3* (range: 33.0 -

78.0)

Control: 60.0 ± 11.3*

(range: 35.0 - 80.0)

Laparoscopic

sphincter-saving

TME (46) 100%

Pre-op RCT

(32) 69.6%

Not specified

Liu et al., 2011 22

Exercise group (11)

Exercise: 4/7

Non-exercise:

Exercise: 55.3 ± 14.3

(range: 27.0 - 82.0)

Anal sphincter

preserving surgery

NR Frequent

defecation


207

50.0%

Non-exercise group

(11) 50.0%

8/3 Non-exercise: 65.7 ±

8.7 (range: 45.0 -

73.0)

(22) 100% and faecal

incontinence

Pucciani et al.,

2008

98

Incontinent patients

(88) 89.8%

Healthy control

(10) 10.2%

Patients: 34/54

Healthy

control: 4/6

Patients: 59.6 ± 6.8*

(range: 46.0 - 73.0)

Healthy control: 57.4

± 6.3* (range: 44.0 -

69.0)

Low anterior rectal

resection (69) 78.4%

Straight coloanal

anastomosis (19)

21.5%

Pre-op RT

(19) 21.6%

Post-op RT

(34) 38.6%

Incontinence

Retrospective

studies

Bartlett et al.,

2011

19 10/9 64.1 (95% CI: 47.0 -

81.3)

Anterior resection

(3) 15.8%

Ultra-low anterior

resection (10) 52.6%

Segmental

colectomy (2)

10.5%

Proctocolectomy (4)

21.1%

NR Bowel

dysfunction

Kim et al., 2011 70 49/21 58.1 ± 10.1 (range:

31.0 - 79.0)

Sphincter-saving

surgery with TME

(70) 100%

Pre-op RT

(30) 42.9%

Post-op RT

(19) 27.1%

Pre-op CT (1)

1.4%

Post-op CT

(25) 35.7%

Pre-op plus

post-op CT

(31) 44.3%

Anterior

resection

syndrome

Abbreviations: M, male; F, female; post-op, postoperative; pre-op, preoperative; RT, radiotherapy; CT, chemotherapy; RCT, radiochemotherapy; TME, total

mesorectal excision; NR, not reported; CI, confidence interval.


208

* Value calculated (not reported in original study)


systematic review

209

Intervention

The types, duration, and frequency of PFM training programs varied among all

studies (Table 8-3). One study used PFM training without biofeedback (Liu et al.,

2011). Six of eight studies provided PFM training with different types of biofeedback:

EMG biofeedback for strengthening (Allgayer et al., 2005); manometric pressure

biofeedback for coordination training (Bartlett et al., 2011; Ho et al., 1996; Ho & Tan,

1997; Laforest et al., 2012); and manometric biofeedback for coordination training,

sensory training, and strength training (Kim et al., 2011). One study used a

multimodal rehabilitative program including PFM training with manometric

biofeedback for strengthening (Pucciani et al., 2008). Length of intervention ranged

from three weeks to 20 months. The frequency of outpatient sessions ranged from

daily to once weekly, and that of home-based sessions ranged from 3-4 times daily to

once daily. In most studies, home practice was encouraged via a formal protocol

(Allgayer et al., 2005; Bartlett et al., 2011; Kim et al., 2011; Liu et al., 2011; Pucciani

et al., 2008) or with general encouragement (Ho et al., 1996; Ho & Tan, 1997).


210

Table 8-3: Intervention programs in reviewed studies

Author and year Intervention

program

Duration (min) Frequency (per

week)

Length Total number

of sessions

Home practice

(Y/N)

Prospective

non-randomized

trials

Allgayer et al.,

2005

Outpatient intensive

PFM training with

intra-anal EMG

biofeedback for

strengthening in

addition to routine

rehabilitation

program

(information,

psychological

support, and light

aerobic exercise)

30 - 40 (PFM

training)

Daily 3 weeks NR Y, PFM training

with biofeedback,

1-hour daily

Ho et al., 1996 Outpatient PFM

training using

manometric

pressure

biofeedback for

coordination

training

60 1 NR 4 Y, encouraged

Ho et al., 1997 Outpatient PFM

training using

manometric

pressure

biofeedback for

60 1 NR 4 Y, encouraged


211

coordination

training

Laforest et al.,

2012

Outpatient PFM

training using

manometric

pressure

biofeedback for

coordination

training

60 1 NR 15 NR

Liu et al., 2011 Home-based PFM

training and 4 ways

to strengthen pelvic

muscles (raising low

back while lying in

bed, standing with

back against a wall,

standing on tiptoes

with support of

chair back, and

holding a rubber

ball between legs)

10 21 - 28 (3 - 4/day) Mean 20.0 (SD

4.7) months

Range: 12.0 - 29.0

months

NR Y, PFM training

Pucciani et al.,

2008

Multimodal

rehabilitative

program *

(pelviperineal

kinesitherapy

[outpatient], PFM

training with

manometric

biofeedback for

strengthening

[home-based],

20 (PFM

training with

biofeedback)

2 (pelviperineal

kinesitherapy)

14 (PFM training

with biofeedback,

2/day)

14 (volumetric

rehabilitation,

2/day)

Daily

(electrostimulation)

4 weeks (PFM

training with

biofeedback)

12 weeks

(electrostimulation)

7

(pelviperineal

kinesitherapy)

Y, PFM training

with biofeedback

and

electrostimulation


212

volumetric

rehabilitation

[home-based], and

electrostimulation

[home-based])

Retrospective

studies

Bartlett et al.,

2011

Outpatient PFM

training using

manometric

pressure

biofeedback for

coordination

training

60 - 90 Daily Mean 7 weeks 4 - 5 Y, individually

prescribed

regimen of

relaxation,

muscle squeezes

and evacuation

techniques, daily,

4 weeks

Kim et al., 2011 Outpatient PFM

training with

manometric

biofeedback for

coordination

training, sensory

training, and

strength training.

NR 1 10 weeks NR Y, not specified

Abbreviation: EMG, electromyography; Y, yes; N, no; NR, not reported; PRS, perineal rectosigmoidectomy; JP, J pouch.

*Each rehabilitative technique was provided based on participant’s manometric reports. Only twelve participants followed all four rehabilitative techniques.


systematic review

213

Outcome measures

All included studies evaluated patient-reported measures of bowel function in terms

of stool frequency, incontinence episodes, and severity of faecal incontinence. Seven

of eight studies assessed stool frequency using a bowel diary Ho et al., 1996; Ho &

Tan, 1997), patient report (Kim et al., 2011; Liu et al., 2011; Pucciani et al., 2008), or

gastrointestinal questionnaires (Laforest et al., 2012). Three studies used a bowel

diary (Bartlett et al., 2011; Ho et al., 1996; Ho & Tan, 1997) to assess number of

incontinence episodes. Five studies included severity of faecal incontinence as a

patient-reported outcome (Allgayer et al., 2005; Bartlett et al., 2011; Kim et al., 2011;

Laforest et al., 2012; Pucciani et al., 2008). However, different faecal incontinence

severity scales including Modified Cleveland Incontinence Score (MCIS) (Allgayer et

al., 2005) and Wexner Incontinence Scale (WIS) (Bartlett et al., 2011; Kim et al.,

2011; Laforest et al., 2012; Pucciani et al., 2008) were used. In addition to the

patient-reported measures of bowel function, six studies used anorectal manometry to

measure anorectal physiological function (Allgayer et al., 2005; Bartlett et al., 2011;

Ho et al., 1996; Ho & Tan, 1997; Kim et al., 2011; Pucciani et al., 2008). Three

studies examined HRQoL after CRC surgery (Bartlett et al., 2011; Laforest et al.,

2012; Liu et al., 2011). The HRQoL was measured by the Functional Assessment of

Cancer Therapy – Colorectal (FACT-C) questionnaire (studies n = 1) (Liu et al.,

2011), Short Form 36 questionnaire (SF-36) (studies n = 1) (Laforest et al., 2012), and

Rockwood Faecal Incontinence Quality of Life Scale (FIQL) (studies n = 2) (Bartlett

et al., 2011; Laforest et al., 2012).

Risk of bias and Level of Evidence

Risk of bias of studies is presented in Table 8-1. The agreement using kappa statistics

between the two independent reviewers on risk of bias assessed using the NOS was

0.972 (percentage agreement, 98.6%). Minor disagreements were resolved with

consensus on 100% of occasions, and on all occasions, scores between reviewers

deviated by only one point. The results of risk of bias assessment showed a mean total

score of 4.9 (SD 1.2, range 3 to 7). Although most criteria within participant selection


systematic review

214

and outcome measure categories were satisfied, the majority of studies were limited

by lack of a non-exposed cohort, lack of independent blinded assessment, and/or

inadequate longer-term follow-up (Allgayer et al., 2005; Bartlett et al., 2011; Ho et al.,

1996; Ho & Tan, 1997; Kim et al., 2011; Laforest et al., 2012; Liu et al., 2011;

Pucciani et al., 2008). Five studies also scored 0 points (out of possible two points) in

the category of comparability of study group (Bartlett et al., 2011; Ho et al., 1996;

Kim et al., 2011; Liu et al., 2011; Pucciani et al., 2008). At best, the level of evidence

was III-2 (range III-2 to IV) (Table 8-1).

8.4.3 Effects of pelvic floor muscle training in patients following colorectal cancer

surgery

Outcomes

Patient-reported outcomes measures

Study results on patient-reported measures of bowel function are presented in Table

8-4. Six studies showed improvement in stool frequency after intervention (Bartlett et

al., 2011; Ho et al., 1996; Ho & Tan, 1997; Kim et al., 2011; Laforest et al., 2012;

Pucciani et al., 2008), and four were statistically significant (p < 0.05) (Bartlett et al.,

2011; Ho et al., 1996; Kim et al., 2011; Laforest et al., 2012). Liu et al. reported no

significant differences in stool frequency between intervention and control groups

after home-based PFM training (Liu et al., 2011). Only one study reported the

long-term follow-up results of stool frequency, which increased at two years after the

final treatment session (Bartlett et al., 2011). Of the three studies that assessed

incontinence episodes, two showed a significant decrease in incontinence episodes (p

< 0.05) after PFM training using manometric biofeedback (Ho et al., 1996; Ho & Tan,

1997). Bartlett et al. reported no significant difference in incontinence episodes after

PFM training using manometric pressure biofeedback (Bartlett et al., 2011).


215

Table 8-4: Results: patient-reported bowel function pre- and post-intervention

Author and year n Measure Pre-intervention

Mean ± SD

Post-intervention

Mean ± SD

p-value

Daily stool frequency

Bartlett et al., 2011 19 Patient bowel

diary

Median 5.0 (IQR

2.9 - 8.6)

Median 2.9 (IQR 1.9

- 4.4)

0.003

Ho et al., 1996

Anterior resection 7 Patient bowel

diary

8.7 ± 5.6* 4.6 ± 3.2* < 0.050

Total colectomy 6 Patient bowel

diary

6.2 ± 5.1* 3.3 ± 3.9* < 0.050

Ho et al., 1997

Incontinence 6 Patient bowel

diary

37.3 ± 31.1* (per

week)

14.4 ± 5.6* (per

week)

NS

Constipation 5 Patient bowel

diary

3.0 ± 1.1* (per

week)

8.9 ± 3.6* (per week) < 0.050

Kim et al., 2011

faecal incontinence 58 Patient report 10.1 ± 4.4 6.3 ± 3.4 < 0.001

incomplete evacuation 8 Patient report 4.1 ± 2.7 3.6 ± 2.5 0.321

frequent defecation 4 Patient report 8.3 ± 2.1 3.5 ± 0.6 0.019

All 70 Patient report 9.4 ± 4.5 5.8 ± 3.3 < 0.001

Laforest et al., 2012

Rehabilitation 22 Gastrointestinal

standardized

questionnaire

NR 2.6 ± 1.3 0.025 (between group)

Control 24 Gastrointestinal

standardized

questionnaire

NR 4.0 ± 2.3 NR


216

Pucciani et al., 2008

Low anterior rectal

resection

69 Patient report 2.9 ± 0.7 1.8 ± 0.6 NS

Straight coloanal

anastomosis

19 Patient report 4.4 ± 0.8 3.4 ± 0.7 NS

Daily incontinence

episodes

Bartlett et al., 2011 19 Patient bowel

diary

Median 1.0 (IQR

0 - 6.5) per week

Median 0.5 (IQR 0 -

3.0) per week

0.183

Ho et al., 1996

Anterior resection 7 Patient bowel

diary

2.7 ± 2.1* 0.4 ± 0.5* < 0.050

Total colectomy 6 Patient bowel

diary

2.4 ± 2.2* 0.5 ± 2.5* < 0.050

Ho et al., 1997

Incontinence 6 Patient bowel

diary

14.8 ± 10.0* (per

week)

1.8 ± 2.0 * (per week) < 0.050

Constipation 5 Patient bowel

diary

NR NR NR

Severity of faecal

incontinence

Allgayer et al., 2005

Irradiated 41 MCIS

questionnaire

7.4 ± 2.2 9.3 ± 2.5 < 0.001

Non-irradiated 54 MCIS

questionnaire

8.6 ± 2.8 11.5 ± 2.6 < 0.001

Bartlett et al., 2011 19 Wexner

Incontinence

Scale

Median 9.0 (IQR

7.0 - 12.0)

Median 6.0 (IQR 3.0

- 8.0)

0.001

Kim et al., 2011

faecal incontinence 58 Wexner 13.6 ± 5.0 8.7 ± 6.0 < 0.001


217

Incontinence

Scale

incomplete evacuation 8 Wexner

Incontinence

Scale

8.7 ± 6.7 7.0 ± 6.5 0.086

frequent defecation 4 Wexner

Incontinence

Scale

12.7 ± 3.2 5.3 ± 3.8 0.170

All 70 Wexner

Incontinence

Scale

13.0 ± 5.2 8.4 ± 6.0 < 0.001

Laforest et al., 2012

Rehabilitation 22 Wexner

Incontinence

Scale

NR 8.3 ± 3.9 0.100 (between group)

Control 24 Wexner

Incontinence

Scale

NR 9.9 ± 3.0* NR

Pucciani et al., 2008

Low anterior rectal

resection

69 Wexner

Incontinence

Scale

11.8 ± 5.1 6.4 ± 3.7 < 0.050

Straight coloanal

anastomosis

19 Wexner

Incontinence

Scale

12.5 ± 4.5 5.8 ± 3.6 < 0.020

All 88 Wexner

Incontinence

Scale

12.3 ± 5.3 4.9 ± 3.9 < 0.030

Abbreviation: n, number of participants; IQR, inter-quartile range; NS, not significant; NR, not reported; MCIS, Modified Cleveland Incontinence Score.

* Value calculated (not reported in original study)


systematic review

218

Five studies used MCIS or WIS to measure severity of faecal incontinence (Allgayer

et al., 2005; Bartlett et al., 2011; Kim et al., 2011; Laforest et al., 2012; Pucciani et al.,

2008). A higher score on MCIS indicates better continence; whereas a higher WIS

score indicates worse continence. In the study by Allgayer et al., the MCIS

significantly increased (p < 0.001) indicating improved incontinence in 95

participants after a 3-week intensive PFM training (Allgayer et al., 2005). The results

of studies using WIS also showed a significant improvement in severity of faecal

incontinence after intervention (p < 0.05) (Bartlett et al., 2011; Kim et al., 2011;

Pucciani et al., 2008), except for Laforest et al., who reported no significant difference

in WIS score between intervention and control groups (Laforest et al., 2012). Two

studies demonstrated conflicting long-term follow-up results of severity of faecal

incontinence (Allgayer et al., 2005; Bartlett et al., 2011). One study reported

maintenance of effects of PFM training with intra-anal EMG biofeedback after 1 year

(Allgayer et al., 2005), and the other study reported increased severity at 2 years

following last treatment session of PFM training using manometric biofeedback,

although the severity remained better than at baseline (Bartlett et al., 2011).

Manometric measures

Six studies used anorectal manometry to measure anorectal physiological function

(Allgayer et al., 2005; Bartlett et al., 2011; Ho et al., 1996; Ho & Tan, 1997; Kim et

al., 2011; Pucciani et al., 2008). The majority reported no significant differences in

mean resting pressure (Allgayer et al., 2005; Bartlett et al., 2011; Ho et al., 1996; Ho

& Tan, 1997; Pucciani et al., 2008), maximum squeeze pressure (Allgayer et al., 2005;

Bartlett et al., 2011; Ho et al., 1996; Ho & Tan, 1997; Pucciani et al., 2008), maximal

tolerable volume (Bartlett et al., 2011; Ho et al., 1996; Ho & Tan, 1997; Pucciani et

al., 2008), volume at initial sensation (Allgayer et al., 2005; Bartlett et al., 2011; Ho et

al., 1996; Ho & Tan, 1997; Pucciani et al., 2008), physiological length (Allgayer et al.,

2005; Ho et al., 1996; Ho & Tan, 1997), and compliance (Ho et al., 1996; Ho & Tan,

1997) in patients after intervention. Only one study by Kim et al. showed significant

differences in mean resting pressure (p = 0.01), maximum squeeze pressure (p =


systematic review

219

0.006), and maximum tolerable volume (p = 0.003) in patients with anterior resection

after PFM training with manometric biofeedback (Kim et al., 2011).

Health-related quality of life (HRQoL)

Three studies examined HRQoL after CRC surgery (Bartlett et al., 2011; Laforest et

al., 2012; Liu et al., 2011). Two studies demonstrated significant improvement in

some domains of HRQoL (Bartlett et al., 2011; Laforest et al., 2012), and one found a

significant difference in total score of HRQoL (p = 0.038) measured using FACT-C

after intervention (Liu et al., 2011). Although not statistically significant, Bartlett et al.

reported further improvement in FIQL scores from the final session at two-year

follow-up.

8.5 Discussion

The aim of our review was to systematically evaluate the evidence for the effect of

PFM training on bowel dysfunction in patients who have undergone CRC surgery. No

RCTs were identified in this review, which reflects the urgent need for RCTs in this

field to provide high levels of evidence to direct PFM training for patients suffering

from this highly distressing problem. Despite the paucity of RCTs and the inherent

methodological shortcomings of the included observational studies, this systematic

review found that PFM training may improve the patient-reported measures of bowel

function and the HRQoL of colon as well as rectal cancer patients following surgery.

The findings in this review are in line with a previous systematic review on treatment

options for improving anorectal function after rectal surgery for patients with or

without cancer (Maris et al., 2013). The previous review examined fifteen studies,

which included heterogeneous treatment options, such as pelvic floor re-education

(seven out of fifteen studies), colonic irrigation, and sacral nerve stimulation.

Although the review reported beneficial effects of conservative therapies on anorectal

function after rectal resection, the papers reviewed were of limited methodological

quality with heterogeneous patient populations, such as patients with rectal cancer,

cervical cancer, and undefined pathology (Maris et al., 2013).


systematic review

220

The findings of our systematic review on specific bowel cancer populations are

consistent with the 5th ICI, which recommends PFM training as an early intervention

in the treatment of faecal incontinence in general adult populations (Bliss et al., 2013).

The results of the present study demonstrate a modest reduction in stool frequency

and incontinence episodes measured by patient bowel diary or patient report after

PFM training. However, most studies that showed significant effects were

underpowered with small numbers of participants or used a retrospective study design;

hence, it is possible that the positive effects of PFM training on patient-reported

measure of bowel function are the results of natural recovery or the Hawthorne effect

(McCarney et al., 2007). Furthermore, the effectiveness of PFM training for the

severity of incontinence in CRC patients after surgery in this study was consistent

with the result of the systematic review conducted by Maris et al. (Maris et al., 2013);

however, our study found that PFM training may be beneficial to certain patient

populations - CRC patients. Only two studies included in our review had evaluated

whether the improvements in the patient-reported measures of bowel function were

maintained over time, and the results were conflicting. Randomized controlled trials

with longitudinal follow-ups are urgently needed to investigate if the long-term

effects of PFM training for patients after CRC surgery are maintained.

In contrast to the beneficial effects of PFM training on the patient-reported measures

of bowel function, all studies except one retrospective study reported no significant

changes in manometric measures following interventions (Allgayer et al., 2005;

Bartlett et al., 2011; Ho et al., 1996; Ho & Tan, 1997; Pucciani et al., 2008). The

inconsistent findings between patient-reported measures and objective manometric

measures of bowel function were consistent with previous studies, which

demonstrated no correlation between anorectal manometry and severity of faecal

incontinence (Lam, Mulder, & Felt-Bersma, 2012; Zutshi, Salcedo, Hammel, & Hull,

2010) or patients’ perception of relief (Deutekom et al., 2005). This may be due to the

multifactorial aetiology of bowel dysfunction or insufficient intensity of PFM training

to achieve a physiological effect. Further mechanistic studies are required to explain

the relationship between changes in symptoms and physiologic measures.


systematic review

221

The findings on HRQoL after PFM training in our review were consistent with

previous studies (Bols et al., 2012; Heymen et al., 2009). As bowel dysfunction may

be the factor that most disturbs patients and impacts their HRQoL after CRC surgery

(Vironen et al., 2006), future studies aimed at investigating the effects of PFM

training on bowel dysfunction in patients with CRC should include HRQoL outcome

measures.

The majority of studies in this review provided PFM training with biofeedback

(Allgayer et al., 2005; Bartlett et al., 2011; Ho et al., 1996; Ho & Tan, 1997; Kim et

al., 2011; Laforest et al., 2012; Pucciani et al., 2008). Only one study focused on PFM

training alone (Liu et al., 2011). Although PFM training is recommended as a

treatment for patients with faecal incontinence (Bliss et al., 2013), a Cochrane review

reported that addition of biofeedback to PFM training may enhance the outcome of

treatment compared to PFM training alone in patients with faecal incontinence after

other conservative managements has failed (Norton & Cody, 2012). Due to limited

number of identified trials in this review, there is not enough evidence to comment on

the effect of PFM training alone and to suggest which modality of biofeedback is

optimal for bowel dysfunction after CRC surgery.

As a dose-response relationship exists in all forms of exercise training, the outcomes

of PFM training may be affected by the duration of treatment and the frequency of

supervision by the therapist (Bø et al., 1990; Bø, 2004a). It is possible that the positive

treatment effects of PFM training on patient-reported measures of bowel function in

this review may be due to the adequate treatment dosage. However, as no significant

changes were found in manometric measures after PFM training, an effective training

dosage for physiological parameters of anorectal function needs to be determined in

future studies. Although home practice was encouraged in most studies (Allgayer et

al., 2005; Bartlett et al., 2011; Ho et al., 1996; Ho & Tan, 1997; Kim et al., 2011;

Pucciani et al., 2008), the content and treatment dosage (frequency and duration) of

the home program were only specified in four studies (Allgayer et al., 2005; Bartlett

et al., 2011; Liu et al., 2011; Pucciani et al., 2008). The adherence to training sessions

and adverse events were not reported by any of the studies included in this review.


systematic review

222

Randomized controlled trials are needed to develop and to investigate the optimal

training regimens and home practice for bowel dysfunction in patient who have

undergone CRC surgery.

Our systematic review adds to a previous systematic review (Maris et al., 2013) in

several ways: the inclusion of two additional studies published in 2011 (Bartlett et al.,

2011; Liu et al., 2011), the inclusion of colon as well as rectal cancer populations, and

a focus on PFM training as the primary intervention. In contrast to the prior review,

we excluded case studies due to the high potential for bias in this study design and

studies which had less than 50% of participants with CRC in order to maintain the

homogeneity of the target population.

8.5.1 Study limitations

The primary limitation is that all studies included were non-randomized observational

studies with small numbers of participants and with the findings predominantly

presented as within-group comparisons. However, according to the ClincalTrials.gov

and the ANZCTR, there are three RCTs currently in progress examining the effect of

PFM training, with or without biofeedback, for patients with rectal cancer, which will

add to the evidence base in the future. This systematic review is further limited by the

moderate methodological quality of the studies and the inclusion of articles published

in English only, which may have led to selection bias. Further limitations include

heterogeneous PFM training interventions program with regards to types of PFM

training, frequency, intensity and duration and few evidence for the long-term effects

of PFM training on bowel dysfunction after CRC surgery.

8.6 Summary

The paucity and limited methodological quality of the evidence does not allow a

robust conclusion to be drawn in support of PFM training in the treatment of bowel

dysfunction of patients following colon or rectal cancer surgery. However, promising

findings from non-randomized studies, suggest that PFM training may be effective in


systematic review

223

improving the patient-reported measures of bowel function and the HRQoL of

patients who have undergone colon or rectal cancer surgery. This intervention can be

viewed as being in the ‘development phase’ of research (Bø & Herbert, 2013; Craig et

al., 2013). Accordingly, the results and the conclusion of this systematic review

should be read with caution due to the lack of RCTs; lack of studies with long-term

follow-up; and the heterogeneity of methodological quality and PFM training

protocols in included studies. Well-designed RCTs with long-term follow-up are

urgently required to provide guidance for clinicians caring for this population in

clinical practice.

8.7 Additional papers published since the systematic review was undertaken

An additional search was run on 17th June 2016 and only two papers were relevant

and retrieved. One is a systematic review, which was published after our systematic

review was accepted for publication. This systematic review by Visser et al. (Visser,

Te Riele, Boerma, van Ramshorst, & van Westreenen, 2014) evaluated the

effectiveness of pelvic floor rehabilitation in improving functional outcome after

sphincter-preserving surgery for rectal cancer and included five studies (Allgayer et

al., 2005; Kim et al., 2011; Laforest et al., 2012; Liu et al., 2011; Pucciani et al., 2008),

which were also included in our systematic review. Although Visser’s systematic

review was limited to patients with rectal cancer, the same conclusion was drawn

(PFM training may be useful in improving continence, stool frequency and HRQoL

for rectal cancer population) (Visser et al., 2014). Only one original article, which met

our inclusion criteria, has been published since our systematic review was published.

This original article is briefly summarised in next section.

8.7.1 Summary of additional study

Kuo and colleagues (Kuo et al., 2015) conducted a prospective observational study to

assess the efficacy and benefits of pelvic rehabilitation programs in terms of

functional outcomes and quality of life for 32 patients with faecal incontinence and

defecation disorders after sphincter saving surgery (a rectal cancer surgery). The


systematic review

224

pelvic rehabilitation programs, which included electrical stimulation and biofeedback,

were conducted in an outpatient hospital setting and performed 2 to 3 times per week

for 4-6 weeks of electrical stimulation and 4-6 weeks of biofeedback. The outpatient

PFM training using manometric pressure biofeedback for coordination training and

sensory training was conducted after completion of electrical stimulation sessions.

Participants with a mean age of 56.5 years (53% males; 78% received neoadjuvant

chemoradiotherapy) experienced significant improvements in maximum squeeze

pressure measured with anorectal manometry (p = 0.014), mean stool frequency per

24h (p < 0.001), use of antidiarrhoeal medications (p < 0.001), stool fragmentation (p

= 0.016), and Wexner Incontinence score (p < 0.001) from pre to post intervention.

Results of this additional study provides further support to the findings of our

systematic review published in 2015 which concluded that pelvic rehabilitation

programs which include electrical stimulation and biofeedback are effective in

improving bowel function and quality of life for patients undergoing sphincter-saving

rectal cancer resection. The additional search shows that the number of studies

investigating the role of PFM training in the management of bowel function following

CRC surgery is slowing emerging. Due to the lack of RCTs, significant gaps still

remain in the literature. Furthermore, the majority of studies to date do not include a

control group; hence, the findings on the improvement in bowel function and HRQoL

following PFM training intervention programs in CRC must be interpreted with

caution. Nevertheless, attention has been drawn to this emerging field of supportive

care in CRC as several RCTs are in progress, which should improve the strength of

evidence in the coming years. The next chapter will provide summary of findings,

strengths and limitations of research design, recommendations and future directions of

CRC research.

Chapter 9. Conclusion and future directions

225


9.1 Overview of main findings

Patients with CRC often experience significant morbidity including distressing

symptoms (anxiety, depression, and bowel, bladder and sexual dysfunction), poor

functional exercise capacity, low levels of PA, and decreased HRQoL following

cancer treatment. The findings in this thesis have demonstrated that:

The APFQ is a valid measurement instrument for use in evaluating bladder

and bowel symptoms in the CRC population.

Age (older) and advanced cancer stage have the potential to predict the

severity of post-operative bladder symptoms in CRC.

The 6MWT and ISWT are valid measures of functional exercise capacity in

patients with CRC.

Patients with CRC experience worsening bowel symptoms, including

incontinence, from pre- to six months post-surgery. They also have low PA

levels both before and after surgery.

Implementation of a general oncology rehabilitation program incorporating the

international PA guidelines is feasible in CRC and associated with

improvements in bladder and bowel symptoms, depression and HRQoL.

Digital rectal examination is positively correlated with both anorectal pressure

manometry and transperineal ultrasound following oncology rehabilitation and

at 6-month follow-up.

Pelvic floor muscle training for patients following surgery for CRC is

associated with improvements in bowel function and HRQoL (level of

evidence III-2 to IV).

In Australia, current clinical pathways or service for patients with CRC do not involve

referral to an oncology rehabilitation program or specific PFM training intervention

following surgery despite the fact that patients have significant unmet needs related to

symptom control and low PA levels. The findings of this thesis support the need for


226

routine general oncology rehabilitation programs and PFM training to be offered to

patients in attempt to improve their bladder and bowel symptoms, minimise

symptoms of depression, maximise HRQoL and promote increases in PA levels. The

findings of this thesis also support the use of the APFQ, 6MWT and ISWT as

measurement instruments for use in the CRC population in research and clinical

practice.

9.2 Strengths and limitations of the present research

The mains strengths of this thesis are (1) highlighting the important issue of uptake

and adherence to exercise guidelines within the CRC population; (2) providing novel

findings on the changes in bladder and bowel symptoms and PFM clinical outcomes

in patients following a general oncology rehabilitation program; (3) identifying

promising outcomes regarding patient benefit from PFM training; (4) confirming the

significant bowel symptoms and inactivity in Australian patients with CRC, which are

comparable with international data; and (5) providing new findings on the validity and

applicability of measurement instruments for functional exercise capacity and pelvic

floor symptoms in patients following CRC surgery.

The limitations of each study have been outlined in the corresponding thesis chapters.

The major limitation is the small sample size making it difficult to conduct subgroup

analyses and generalize results. The pilot or exploratory nature (not powered) of all

studies and the lack of a true control (comparison) group in Study 4 and Study 5 limit

the ability to draw definitive conclusions. However, with a high proportion of patients

with colon cancer included in our studies, our findings add valuable information to the

current literature as the majority of research in this field has focused on rectal cancer

only.

9.3 Future directions

Colorectal cancer is the third most prevalent cancer worldwide, with more than 3.5

millions of CRC survivors (Ferlay et al., 2013). The number of patients living in the

community with CRC or as survivors is steadily increasing. Minimising disease


227

burden and maximizing patient function and HRQoL are of upmost important to this

large patient population.

As the number of CRC survivors continues to grow (Miller et al., 2016), survivorship

care including oncology rehabilitation for CRC has become a major area of interest

(Jorgensen, Young, & Solomon, 2015). According to the American Cancer Society

CRC survivorship care guidelines (El-Shami et al., 2015), the evidence (level I) is

strong for clinicians to recommend PA to their patients, and to refer on to specialists

for psychosocial support and or rehabilitation as needed. An important question

remains regarding the impact of exercise training on survival in CRC. There is a small

amount of evidence on the association between PA levels and CRC survival

(Meyerhardt et al., 2006; Heseltine et al., 2006), however the effects of a general

oncology rehabilitation program on survival remain unknown. Well-designed RCTs

with long-term follow-up are urgently required to provide guidance for clinicians

caring for CRC populations in clinical practice. A search of the clinical trial registry

databases (ClinicalTrials.gov and the Australian and New Zealand Clinical Trials

Registry) showed that several RCTs on exercise interventions for survival in patients

with CRC are currently in progress, which will add new evidence to this emerging

field of CRC oncology rehabilitation in the near future. If conclusions can be found,

such that participation in rehabilitation is associated with prolong life, this will change

current referral pathways.

In addition, further work is required to determine if there are specific subgroups

within the CRC population (i.e. low functional exercise capacity or PA levels or high

levels of comorbidity at baseline) who are more likely to respond to exercise

interventions and develop a risk classification system to determine who is at greatest

need (Dittus et al., 2015).

Despite the strong evidence for PA and reduced sedentary time, there is limited

evidence (level III) for optimal management of bowel problems in CRC (El-Shami et

al., 2015). Although our findings in Study 4 and Study 6 add to the evidence by

showing that an oncology rehabilitation program or PFM training with or without

biofeedback may be beneficial for bladder and bowel symptoms, Study 4 is a pilot


228

non-randomized quasi-control study and Study 6 is a systematic review including

nonrandomized observational studies with small numbers of participants. There were

no RCTs identified in the systematic review reflecting a need for higher levels of

evidence in this field to direct general oncology rehabilitation or PFM training for

patients suffering from the highly distressing bowel problems following CRC surgery.

However, according to the ClincalTrials.gov and the ANZCTR, there are RCTs

currently in progress examining the effect of PFM training with or without

biofeedback for patients with CRC, which will provide valuable evidence regarding

the role of PFM training in CRC rehabilitation. If the efficacy of the PFM training is

established, best practice for CRC rehabilitation may be developed and the referral

pathways and clinical service delivery for this population may change.

Across the cancer care continuum (Taplin et al., 2012), there are three phases

post-cancer diagnosis (i.e. pretreatment, treatment, and survivorship/end of life)

(Courneya & Friedenreich, 2007). Cancer prehabilitation is part of the cancer care

continuum that occurs between cancer diagnosis and the beginning of primary

treatment and provides interventions to promote physical and psychological health

and to reduce the incidence and/or severity of future impairments (Silver, Baima, &

Mayer, 2013). Research is emerging to investigate the impact of prehabilitation on

functional recovery in patients undergoing CRC surgery (Bruns et al., 2016; Gillis et

al., 2014; Li et al., 2013). A systematic review by Bruns et al.(Bruns et al., 2016)

identified five studies with moderate methodological quality and showed that

prehabilitation can improve physical condition (walking distance and respiratory

endurance) in patients aged over 60 years undergoing CRC surgery. However, no

studies have included PFM training as a component of the prehabilitation program

(Bruns et al., 2016). Although there is emerging evidence (Kim et al., 2015; Kye, Kim,

Kim, Yoo, & Cho, 2016) for the role of PFM training with biofeedback during the

temporary stoma period on bowel function in patients with CRC following stomal

closure, the results are contradictory with one study showing no effect of PFM

training on preventing bowel dysfunction after temporary stoma reversal (Kye et al.,

2016) and one reporting improvements in bowel symptoms 12 months after ileostomy

closure (Kim et al., 2015). As bowel symptoms are common in patients following


229

CRC treatment, future studies should focus on the prevention of deterioration in

bowel symptoms following CRC surgery and determine the optimal timing of the

PFM training.

As the majority of participants in Study 4 felt that the general oncology rehabilitation

program was beneficial, future RCTs should consider investigating the

implementation and translations of such rehabilitation program to other pelvic cancers

(i.e. urological and gynaecological cancers).

“Excellent to take me from loss to confidence in how to manage my body. Great

opportunity to share issues relating to cancer with others. Valuable information and a

good time frame to learn new habits.” (Participant A)

“The entire program is well run and extremely beneficial. It should be compulsory for

all cancer patients!! I am very pleased I did it and grateful for what it taught me. All

the presenters were highly qualified, patient and caring. Quietly motivating!”

(Participant B)

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230

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Appendix 4.1

282

Appendices

Appendix 4.1 Ethics Approval Documentation (Study 2)

Appendix 4.2

283

Appendix 4.2 Data collection sheets (Study 2)

VALIDATION OF EXERCISE TESTS TO BE USED WITH PATIENTS WITH

LUNG AND COLORECTAL CANCER

HREC 2013.052

Version 2

DATA COLLECTION SHEET

Participant trial number: ___________

Date of consent: ___________

Recruitment therapist: ___________

MEDICAL DEMOGRAPHICS

Please circle the number or tick the box (to be completed from the medical history)

Age ___________

Gender 1 = male 2 = female

Cancer type 1 = lung cancer 2 = colorectal cancer

Lung cancer histological

type

1 = squamous 2 = adenocarcinoma

3 = large cell

5 = not lung cancer

4 = other: ___________

Colorectal cancer

histological type

1 = medullary carcinoma 2 = adenocarcinoma

3 = mucinous (colloid)

adenocarcinoma

5 = squamous cell (epidermoid)

carcinoma

7 = small cell (oat cell)

carcinoma

9 = not colorectal cancer

4 = signet-ring cell carcinoma

6 = adenosquamous carcinoma

8 = undifferentiated carcinoma

10 = other: ___________

TNM stage of cancer (lung

and colorectal)

1 = stage IA includes: T1a/bN0M0

2 = stage IB includes: T2aN0M0

3 = stage IIA includes: T2bN0M0; T1a/bN1M0; T2aN1M0

4 = stage IIB Includes: T2bN1M0; T3N0M0

5 = stage IIIA Includes: T1a/bN2M0; T2a/bN2M0; T3N1/2M0;

T4N0/1M0

6 = stage IIIB Includes: Any T N3 MO; T4 any N M0

Appendix 4.2

284

7 = stage IV Includes: Any M1

Australian

Clinicopathological

colorectal cancer stage

(ACPS)

1 = ACPS A

2 = ACPS B

3 = ACPS C

4 = ACPS D


Date of cancer diagnosis ____/____/ 201_

Date cancer treatment commenced ____/____/ 201_

Date cancer treatment concluded ____/____/ 201_

Type of chemotherapy or

radiotherapy

1 = chemo + radio 2 = radio palliative < 5 fractions

3 = radio HD (radical) 4 = chemo only

5 = no chemo or radio 6 = other

Date of surgery ____/____/ 201_

Length of hospital stay: ___________

(in days – inc day admitted and day discharge)

Type of thoracic surgery 1 = lobectomy

2 = pneumonectomy

3 = segmentectomy

4 = wedge resection

5 = other: ___________

6 = not lung cancer

Type of colorectal surgery 1 = colectomy

2 = anterior resection

3 = abdominal perineal excision of rectum

4 = other: ___________


Appendix 4.2

285

Colinet comorbidity Score

total score

= (please add up scores on right)

TOBACCO CONSUMPTION

– lifelong consumption of at least 100 cigs

7 points

DIABETES MELLITUS

– treated with oral hypoglycaemic or insulin

5 points

RENAL INSUFFICIENCY

– creatine clearance lower than 60ml

4 points

RESPIRATORY

– 1 or more of the following:

history of TB, PE or pneumonia, asthma, pul embolism, chronic COPD,

(FEV1) <1.5l

1 point

CARDIOVASCULAR

– 1 or more of the following:

congestive HF, ischemic cardiomyopathy +/- MI, severe cardiopathy, arrhythmia requiring chronic tx, hx of cerobascular disease, hypertension

or peripheral vascular disease

1 point

NEOPLASTIC

– Previous Hx of cancer excluding; basal cell carcinoma of the skin and in

situ carcinoma of the cervix.

1 point

ALCOHOLISM –

> 80g (4-7 sd) per day Men > 40g (2-4 sd) per day Women

1 point

Appendix 4.2

286

SOCIAL DEMOGRAPHICS

Please circle the number or tick the box (to be completed with participant)

Which of the following best describes your social situation?

1. a

)

Home alone, independent

2. b

)

Home with family

3. c

)

Home with supports

4. d

)

Retirement village

5. e

)

Nursing home - low level care

6. f

)

Nursing home - high level care

7. i

)

Other: ___________

Which of the following best describes your current employment status?

1. Working full time

2. Working part time

3. Sick leave/ leave of absence – temporary

4. Sick leave/ leave of absence – permanent

5. Not employed/ taking time off work

6. Retired

7. Home duties

8. Studying

9. Other: ___________

Which of the following best describes your smoking status?

1. Never smoked

2. Quit smoking longer than 8 weeks ago

3. Current smoker

How many years have you/ did you smoked for? __________

How many packets per day on average do you / did you smoke? ___________

Appendix 4.2

287

What is the highest level of formal education that you obtained?

1. No formal schooling

2. Some primary schooling

3. Finished primary schooling

4. Some secondary or high school

5. Completed secondary or high school

6. Some trade, community or TAFE college

7. Completed trade, community, TAFE college

8. Some university

9. Completed Bachelor’s degree

10. Completed Masters or PhD degree

11. Other

Have you experienced any unexpected weight loss within the last 12 months?

1. No

2. Yes, if so roughly how many kg___________

How active are you?

0. Fully active

1. Walking, but only can do light work

2. Rest in bed LESS than half the day, do not work

but can care for self

3. Rest in bed MORE than half the day, and only

partially cares for self

4. Bedridden

Do you have any limitations to walking as far as you need to?

1. No

2. Yes, if so

How far can you walk on average?__________meters

Appendix 4.2

288

Do you need an aid to walk with?

1. No

2. Walking stick outdoors only

3. Walking stick

4. Walking frame

5. Other

In the last week, have you gone for a walk outside for more than 10 minutes? For example, this

could be walking the dog, walking to the shops or walking for exercise. This does not include

walking you do as part of your job or walking when you are doing the gardening?

1. No

2. Yes

If so:

How many times in the last week _____________days

On average for how long at one time __________minutes

How many hours did you watch television or videos in the last week?

= average_______________ hours per

day

Appendix 4.2

289

SIX MINUTE WALK TEST RECORDING SHEET (accessed from the Pulmonary Rehabilitation Toolkit http://www.pulmonaryrehab.com.au)

Walk 1 Walk 2

Time:___________ Time:___________

Bronchodilator/time since last dose:______ Bronchodilator/time since last

dose:___

BP

__/__

mmH

g

SupplementalOx

ygen

____l/min

Gait Aid

_________

__

BP

__/__

mmH

g

SupplementalOx

ygen

____l/min

Gait Aid

_________

___

Time (mins) SpO2

(%)

Dyspnoea

(Borg)

Rests Time

(mins)

SpO2

(%)

Dyspnoea

(Borg)

Rests

Rest Rest

1 1

2

2

3

3

4

4

5

5

6 6

Recovery 1 Recovery

1

Distance (m):________________ Distance (m):______________

Limiting factor to the test: Limiting factor to the test:

SOB Low SpO2 SOB Low SpO2

Leg fatigue Other: Leg fatigue Other:

Reason for test non-completion:

Patient deceased Patient lost to follow up

Patient refused Patient confusion

Other: ______________________

Appendix 4.2

290

INCREMENTAL SHUTTLE WALKING TEST RECORDING SHEET (accessed from the Pulmonary Rehabilitation Toolkit http://www.pulmonaryrehab.com.au)

Age: Predicted HRmax (220-age):

Walk 1 Walk 2

Time:___________ Time:___________

Bronchodilator/time since last dose:______ Bronchodilator/time since last dose:___

BP

__/__

mmH

g

SupplementalOx

ygen

____l/min

Gait Aid

_________

__

BP

__/__

mmH

g

SupplementalOx

ygen

____l/min

Gait Aid

_________

___

Time

mins

SpO2 HR Dyspnoea Time

mins

SpO2 HR Dyspnoea

Rest Rest

1 1

2 2

3 3

4 4

5

5

6 6

7 7

8 8

9 9

10 10

11 11

12 12

Recovery 1

Recovery

1

2 2

Number of shuttles completed: _______ Number of shuttles completed:

______

Distance (number of shuttles x 10):_____ Distance (m): _______


SOB Low SpO2 SOB Low SpO2

Leg fatigue Other: Leg fatigue Other:

Appendix 4.2

291

Tick shuttles completed during test:

Clinical notes for using the recording sheet:

You do not need to record SpO2%, heart rate and dyspnoea every minute but there is

space on the table above if you wish to.

The box diagram above is designed to make sure you don’t lose track of the number

of shuttles completed. Tick a box each time the patient reaches a cone.

Level 1

Level 2

Level 3

Level 4

Level 5

Level 6

Level 7

Level 8

Level 9

Level 10

Level 11

Level 12

Level 13

Level 14

Level 15

Level 16

Level 1

Level 2

Level 3

Level 4

Level 5

Level 6

Level 7

Level 8

Level 9

Level 10

Level 11

Level 12

Level 13

Level 14

Level 15

Level 16

Appendix 4.2

292

ENDURANCE SHUTTLE WALKING TEST RECORDING SHEET (accessed from the Pulmonary Rehabilitation Toolkit http://www.pulmonaryrehab.com.au)

Therapist initials______________

Number and grade/classification of therapists taken to complete assessment:______

START time for this test:______END time for this test:______Test duration (min)___

Gait aid___________ BP________________

ESWT level:_____________

Time

mins

SpO2 (%) HR Rests Dyspnoea (Borg) Leg fatigue

(Borg)

Rest

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

Appendix 4.2

293

20

Test end

Recovery 1

Time for HR to recover to

resting level (min

Total time walked: ______ (this excludes the 90second warm up)

Limiting factor to the test:

SOB Low SpO2 Leg fatigue

Other:

Appendix 4.2

294

BODY COMPOSITION RECORDING SHEET

Participants with a permanent pacemaker or defibrillator must be excluded

from this test

Arm circumference __________cm (non dominant arm, measure midpoint between AC shoulder joint and olecranon while arm is resting by side )

Calf circumference __________cm (widest part around calf )

Height: ___________cm

Weight: ___________kg

Total body water: ____________L _________%

Extracellular fluid: ____________L _________%

Intracellular fluid: ____________L _________%

Fat free mass: ____________kg _________%

Fat mass: ____________kg _________%

BMI: ___________kg/m2

Ri: ___________

Re: ___________

Rinf: ___________

Appendix 4.2

295

EORTC QLQ-C30 (Version 3)

We are interested in some things about you and your health. Please answer all of the questions

yourself by circling the number that best applies to you. There are no "right" or "wrong"

answers. The information that you provide will remain strictly confidential.

Not

at all

A

Little

Quite

a bit

Very

much

1 Do you have any trouble doing strenuous activities,

like carrying a heavy shopping bag or a suitcase?

1 2 3 4

2 Do you have any trouble taking a long walk? 1 2 3 4

3 Do you have any trouble taking a short walk outside

of the house?

1 2 3 4

4 Do you need to stay in bed or a chair during the day? 1 2 3 4

5 Do you need help with eating, dressing, washing

yourself or using the toilet?

1 2 3 4

During the past week: Not

at all

A

Little

Quite

a bit

Very

much

6 Were you limited in doing either your work or other

daily activities?

1 2 3 4

7 Were you limited in pursuing your hobbies or other

leisure time activities?

1 2 3 4

8 Were you short of breath? 1 2 3 4

9 Have you had pain? 1 2 3 4

10 Did you need to rest? 1 2 3 4

11 Have you had trouble sleeping? 1 2 3 4

12 Have you felt weak? 1 2 3 4

13 Have you lacked appetite? 1 2 3 4

14 Have you felt nauseated? 1 2 3 4

15 Have you vomited? 1 2 3 4

Appendix 4.2

296

During the past week: Not at

all

A

Little

Quite

a bit

Very

much

16 Have you been constipated? 1 2 3 4

17 Have you had diarrhea? 1 2 3 4

18 Were you tired? 1 2 3 4

19 Did pain interfere with your daily activities? 1 2 3 4

20 Have you had difficulty in concentrating on things,

like reading a newspaper or watching television?

1 2 3 4

21 Did you feel tense? 1 2 3 4

22 Did you worry? 1 2 3 4

23 Did you feel irritable? 1 2 3 4

24 Did you feel depressed? 1 2 3 4

25 Have you had difficulty remembering things? 1 2 3 4

26 Has your physical condition or medical treatment

interfered with your family life?

1 2 3 4


interfered with your social activities?

1 2 3 4


caused you financial difficulties?

1 2 3 4

For the following questions please circle the number between 1 and 7 that best applies

to you

29 How would you rate your overall health during the past week?

1 2 3 4 5 6 7

Very poor Excellent

30 How would you rate your overall quality of life during the past week?

1 2 3 4 5 6 7

Very poor Excellent

Appendix 4.2

297

EORTC QLQ-CR29 (COLORECTAL

MODULE)


all

A

Littl

e

Quite

a bit

Very

much

31 Did you urinate frequently during the day? 1 2 3 4

32 Did you urinate frequently during the night? 1 2 3 4

33 Have you had any unintentional release (leakage)

of urine?

1 2 3 4

34 Did you have pain when you urinated? 1 2 3 4

35 Did you have abdominal pain? 1 2 3 4

36 Did you have pain in your buttock/anal/rectum? 1 2 3 4

37 Did you have a bloated feeling in your abdomen? 1 2 3 4

38 Have you had blood in your stools? 1 2 3 4

39 Have you had mucus in your stools? 1 2 3 4

40 Did you have a dry mouth? 1 2 3 4

41 Have you lost hair as a result of your treatment? 1 2 3 4

42 Have you had problems with your sense of taste?

1 2 3 4


all

A

Littl

e

Quite

a bit

Very

much

43 Were you worried about your health in the future? 1 2 3 4

44 Have you worried about your weight?

1 2 3 4

45 Have you felt less physically attractive as a result

of your disease or treatment?

1 2 3 4

46 Have you been feeling less feminine / masculine as

a result of your disease or treatment?

1 2 3 4

47 Have you been dissatisfied with your body?

1 2 3 4

48 Do you have a stoma bag (colostomy/ileostomy)?

(please circle the correct answer)

yes no

Appendix 4.2

298


all

A

Littl

e

Quite

a bit

Very

much

Answer these questions ONLY IF YOU HAVE A STOMA BAG, if not please continue

below:

49 Have you had unintentional release of

gas/flatulence from your stoma bag?

1 2 3 4

50 Have you had leakage of stools from your stoma

bag?

1 2 3 4

51 Have you had sore skin around your stoma?

1 2 3 4

52 Did frequent bag changes occur during the day?

1 2 3 4

53 Did frequent bag changes occur during the night?

1 2 3 4

54 Did you feel embarrassed because of your stoma?

1 2 3 4

55 Did you have problems caring for your stoma?

1 2 3 4

Answer these questions ONLY IF YOU DO NOT HAVE A STOMA BAG:


gas/flatulence from your back passage?

1 2 3 4

50 Have you had leakage of stools from your back

passage?

1 2 3 4

51 Have you had sore skin around your anal area?

1 2 3 4

52 Did frequent bowel movements occur during the

day?

1 2 3 4

53 Did frequent bowel movements occur during the

night?

1 2 3 4

54 Did you feel embarrassed because of your bowel

movement?

1 2 3 4

Appendix 4.2

299

During the past 4 weeks: Not at

all

A

Little

Quite

a bit

Very

muc

h

For men only:

56 To what extent were you interested in sex? 1 2 3 4

57 Did you have difficulty getting or maintaining an

erection?

1 2 3 4

For women only:


59 Did you have any pain or discomfort during

intercourse?

1 2 3 4

Appendix 4.2

300

Australian Pelvic Floor Questionnaire

Please tick your most appropriate answer.

Consider your experiences during the last months.

Note: If you are a male, please skip ‘Prolapse Section’ and ‘Sexual Function Section’

Bladder Section

Q1 How many times do you pass

urine in the day?

[ ] up to 7

[ ] between 8 – 10

[ ] between 11 – 15

[ ] > 15

Q2 How many times do you get

up at night to pass urine?

[ ] 0 – 1

[ ] 2

[ ] 3

[ ] > 3

Q3 Do you wet the bed before

you wake up at night?

[ ] never

[ ] occasionally (< 1 x week)

[ ] frequently (≥ 1 x week)

[ ] always (every night)

Q4 Do you need to rush or hurry

to pass urine when you get the

urge?

[ ] never



[ ] daily

Q5 Does urine leak when you

rush or hurry to the toilet? Do you

not make it in time?

[ ] never



[ ] daily

Q6 Do you leak with coughing,

sneezing, laughing or exercising?

[ ] never

[ ] occasionally (< 1/week)

[ ] frequently ( 1/week)

[ ] daily

Q7 Is your urinary stream (urine

flow) weak, prolonged or slow?

[ ] never



[ ] daily

Q8 Do you have a feeling of

incomplete bladder emptying?

[ ] never



[ ] daily

Q9 Do you need to strain to

empty your bladder?

[ ] never



[ ] daily

Q10 Do you have to wear pads

because of urinary leakage?

[ ] none – never

[ ] as a precaution

[ ] with exercise/during a cold

[ ] daily

Q11 Do you limit your fluid

intake to decrease urinary

leakage?

[ ] never

[ ] before going out

[ ] moderately

[ ] always

Q 12 Do you have frequent

bladder infections?

[ ] no

[ ] 1 – 3 per year

[ ] 4 – 12 per year

[ ] > 1 per month

Q13 Do you have pain in your

bladder or urethra when you

empty your bladder?

[ ] never



[ ] daily

Q 14 Does urine leakage affect

your routine activities (recreation,

socializing, sleeping, shopping

etc.)?

[ ] not at all

[ ] slightly

[ ] moderately

[ ] greatly

Q 15 How much does your

bladder problem bother you?

[ ] not at all

[ ] slightly

[ ] moderately

[ ] greatly

Bowel Section

Q 16 How often do you usually

open your bowels?

[ ] every other day or daily

[ ] less than every 3 days

[ ] less than once per week

[ ] more than once a day

Q 17 What is the consistency of

your usual stool?

[ ] soft

[ ] firm

[ ] hard (pebbles)

[ ] watery

[ ] variable

Q 18 Do you have to strain a lot

to empty your bowels?

[ ] never



[ ] daily

Q 19 Do you use laxatives to

empty your bowels?

[ ] never



[ ] daily

Q 20 Do you feel constipated?

[ ] never



[ ] daily

Q 21 When you get wind or

flatus, can you control it or does

wind leak?

[ ] never



[ ] daily

Appendix 4.2

301

Q 22 Do you get an

overwhelming sense of urgency to

empty your bowels?

[ ] never



[ ] daily

Q 23 Do you leak watery stool

when you don’t mean to?

[ ] never



[ ] daily

Q 24 Do you leak normal stool


[ ] never



[ ] daily

Q 25 Do you have the feeling of

incomplete bowel emptying?

[ ] never



[ ] daily

Q 26 Do you have to use finger

pressure to help empty your

bowels?

[ ] never



[ ] daily

Q 27 How much does your bowel

problem bother you?

[ ] not at all

[ ] slightly

[ ] moderately

[ ] greatly

Prolapse Section (women only)

Q 28 Do you have a sensation of

tissue protrusion or a lump or

bulging in your vagina?

[ ] never



[ ] daily

Q 29 Do you experience vaginal

pressure or heaviness or a

dragging sensation?

[ ] never



[ ] daily

Q 30 Do you have to push your

prolapse back in order to empty

your bladder?

[ ] never



[ ] daily


prolapse back to empty your

bowels?

[ ] never



[ ] daily


prolapse problem bother you?

[ ] not at all

[ ] slightly

[ ] moderately

[ ] greatly

Sexual Function Section (women only)

Q 33 Are you sexually active?

[ ] no

[ ] < 1 x week

[ ] 1 x week

[ ] daily or most days

If you are not sexually active,

please answer Q34 and Q42 only.

Q 34 If you are not sexually

active, please tell us why:

[ ] I do not have a partner

[ ] I am not interested

[ ] my partner is unable

[ ] vaginal dryness

[ ] too painful

[ ] embarrassment due to

bladder, bowel or prolapse

[ ] other reasons:

Q 35 Do you have sufficient

natural vaginal lubrication during

intercourse?

[ ] yes

[ ] no

Q 36 During intercourse vaginal

sensation is:

[ ] normal / pleasant

[ ] minimal

[ ] painful

[ ] none

Q 37 Do you feel that your

vagina is too loose or lax?

[ ] never

[ ] occasionally

[ ] frequently

[ ] always

Q 38 Do you feel that your vagina

is too tight?

[ ] never

[ ] occasionally

[ ] frequently

[ ] always

Q 39 Do you experience pain with

sexual intercourse?

[ ] never

[ ] occasionally

[ ] frequently

[ ] always

Q 40 Where does the pain

during intercourse occur?

[ ] not applicable, I do not

have pain

[ ] at the entrance to the

vagina

[ ] deep inside, in the pelvis

[ ] both at the entrance and in

the pelvis

Q 41 Do you leak urine during

sexual intercourse?

[ ] never

[ ] occasionally

[ ] frequently

[ ] always

Q 42 How much do these sexual issues bother you?

[ ] not applicable, I do not have a problem

[ ] not at all

Appendix 4.2

302

[ ] slightly

[ ] moderately

[ ] greatly

Appendix 4.2

303

INTERNATIONAL CONSULTATION ON INCONTINENCE

QUESTIONNAIRE-BOWELS

Many people experience bowel accidents or bowel leakages. We would be grateful if

you could answer the following questions, thinking about how you have been over the

PAST THREE MONTHS

Bowel pattern

3 On average how many times do you open your bowels in 24 hours?

(Tick one box for ‘usual’ and tick one box for ‘at worst’)

(a) (b)

Usual At worst

less than once 1 1

one to three times 2 2

three to ten times 3 3

ten or more times 4 4

(c) How much does this bother you?

Please ring a number between 0 (not at all) and 10 (a great deal)

0 1 2 3 4 5 6 7 8 9 10

not at all a great deal

4 How often do you open your bowels during the night from going to bed to

sleep until you get up in the morning? (Tick one box)

(a)

never 0

once 1

twice 2

three times 3

four or more times 4

(b) How much does this bother you?


0 1 2 3 4 5 6 7 8 9 10


Appendix 4.2

304

5 Do you have to rush to the toilet when you need to open your bowels?

(Tick one box)

(a)

never 0

rarely 1

some of the time 2

most of the time 3

always 4



0 1 2 3 4 5 6 7 8 9 10


6 Do you use medications (tablets or liquids) to stop you opening your

bowels? (Tick one box)

(a)

never 0

less than once a month 1

less than once a week 2

less than once a day 3

about once a day 4

several times a day 5



0 1 2 3 4 5 6 7 8 9 10


Appendix 4.2

305

7

Do you experience pain/soreness around your back passage? (Tick one box)

(a)

never 0

rarely 1

some of the time 2

most of the time 3

always 4



0 1 2 3 4 5 6 7 8 9 10


Bowel pattern score: sum scores 3a - 7a

Bowel control

8 Do you experience any staining of your underwear or need to wear pads

because of your bowels? (Tick one box)

(a)

never 0




everyday 4



0 1 2 3 4 5 6 7 8 9 10


Appendix 4.2

306

9 Are you able to control watery or loose stool leaking from your back

passage? (Tick one box)

(a)

always 0

most of the time 1

some of the time 2

rarely 3

never 4



0 1 2 3 4 5 6 7 8 9 10


10 Are you able to control accidental loss of formed or solid stool from your

back passage? (Tick one box)

(a)

always 0

most of the time 1

some of the time 2

rarely 3

never 4



0 1 2 3 4 5 6 7 8 9 10


Appendix 4.2

307

11 Are you able to control wind (flatus) escaping from your back passage?

(Tick one box)

(a)

always 0

most of the time 1

some of the time 2

rarely 3

never 4



0 1 2 3 4 5 6 7 8 9 10


12 Are you able to control mucus (discharge) leaking from your back

passage?

(Tick one box)

(a)

always 0

most of the time 1

some of the time 2

rarely 3

never 4



0 1 2 3 4 5 6 7 8 9 10


Appendix 4.2

308

13 Do you have bowel accidents when you have no need to open your bowels?

(Tick one box)

(a)

never 0

rarely 1

some of the time 2

most of the time 3

always 4



0 1 2 3 4 5 6 7 8 9 10


14 Are your bowel accidents or leakages unpredictable? (Tick one box)

(a)

never 0

rarely 1

some of the time 2

most of the time 3

always 4



0 1 2 3 4 5 6 7 8 9 10


Bowel control score: sum scores 8a – 14a

Appendix 4.2

309

Other bowel symptoms

15 Using the pictures please indicate how your bowel movements are most

of the time? (Tick all boxes that apply)

(a)

separate hard lumps like nuts (hard to pass) 1

sausage-shaped but lumpy 2

like a sausage but with cracks on its surface 3

like a sausage or snake – smooth and soft 4

soft blobs with clear cut edges (easy to pass) 5

fluffy pieces with ragged edges, a mushy stool 6

watery, no solid pieces 7



0 1 2 3 4 5 6 7 8 9 10


16 Do you need to strain to open your bowels? (Tick one box)

Appendix 4.2

310

17 Is the possibility of having a bowel accident on your mind? (Tick one box)

(a)

never 0

rarely 1

some of the time 2

most of the time 3

always 4



0 1 2 3 4 5 6 7 8 9 10


Sexual impact

(a)

never 0

rarely 1

some of the time 2

most of the time 3

always 4



0 1 2 3 4 5 6 7 8 9 10


Appendix 4.2

311

18 Do you restrict your sexual activities because of your bowels? (Tick one

box)

(a)

never 0

rarely 1

some of the time 2

most of the time 3

always 4

not applicable 5



0 1 2 3 4 5 6 7 8 9 10


Quality of life

19 Do your bowels cause you to feel embarrassed? (Tick one box)

(a)

never 0

rarely 1

some of the time 2

most of the time 3

always 4



0 1 2 3 4 5 6 7 8 9 10


20 Do your bowels cause you to make sure you know where toilets are?

Appendix 4.2

312

(Tick one box)

(a)

never 0

rarely 1

some of the time 2

most of the time 3

always 4



0 1 2 3 4 5 6 7 8 9 10


21 Do your bowels cause you to make plans according to your bowels?

(Tick one box)

(a)

never 0

rarely 1

some of the time 2

most of the time 3

always 4



0 1 2 3 4 5 6 7 8 9 10


22 Do your bowels cause you to stay home more often than you would like?

Appendix 4.2

313

(Tick one box)

(a)

never 0

rarely 1

some of the time 2

most of the time 3

always 4



0 1 2 3 4 5 6 7 8 9 10


23. Overall, how much do your bowels interfere with your everyday life?


0 1 2 3 4 5 6 7 8 9 10


Quality of life score: sum scores 19a -23

24

Please use the space below to describe any worries you have about

bowel accidents or leakages, what you think may have caused your

bowel accidents or leakages, or anything else you think we should

know.

Appendix 5.1

314


Appendix 5.1

315

Appendix 5.1

316

Appendix 5.1

317

Appendix 5.1

318

Appendix 5.2

319

Appendix 5.2 Data collection sheets (Study 3)

DEMOGRAPHICS

(Please circle number or tick box)

DEMOGRAPHICS

Date of birth

(ddmmyear)

Age (year)

Gender 1 = Male 2 = Female

Height (cm)

Weight (kg) T1 T2 T3

Smoking

status

1 = Never smoked 2 = Ex smoker 3 = Current smoker

Number of years

smoked

Number of packets/day

MEDICAL HISTORY

Medical conditions Charlson Comorbidity Index

assigned weights

� Myocardial Infarction 1

� Congestive heart failure

� Peripheral vascular disease

� Cerebrovascular disease

� Dementia

� Chronic obstructive pulmonary disease

� Connective tissue disease

� Peptic ulcer disease

� Mild liver disease

� Diabetes

� Hemiplegia 2

� Moderately severe renal disease

� Diabetes with end-organ damage

� Any tumour (within last 5 years)

� Lymphoma

� Leukaemia

� Moderately severe liver disease 3

� Metastatic solid tumour 6

� AIDS

SURGICAL HISTORY

Past surgical history Date (ddmmyear)

�1. bladder surgery (e.g. colposuspension/sling etc)

�2. gynaecological surgery (e.g. hysterectomy / prolapse repair)

�3. bowel surgery (e.g. rectal prolapse / bowel incontinence)

�4. anal surgery (e.g. haemorrhoids / anal fissures repair)

�5. kidney surgery

�6. back surgery

�7. other surgery __________________________

Appendix 5.2

320

ONCOLOGY

Histology T1

Stage of

colorectal

cancer

1 = Stage I includes: T1-T2, N0, M0 (Dukes A)

2 = Stage IIA includes: T3, N0, M0 (Dukes B)

3 = Stage IIB includes: T4a, N0, M0 (Dukes B)

4 = Stage IIC includes: T4b, N0, M0 (Dukes B)

5 = Stage IIIA includes: T1-T2, N1, M0; T1, N2a, M0

(Dukes C)

6 = Stage IIIB includes: T3-T4a, N1, M0; T2-T3, N2a,

M0; T1-T2, N2b, M0 (Dukes C)

7 = Stage IIIC includes: T4a, N2a, M0; T3-T4a, N2b,

M0; T4b, N1-N2, M0 (Dukes C)

8 = Metastases

9 = Recurrent cancer

Level of

tumour

� Colon

� Rectum

Adjuvant

treatments

T1 T2

1 = preoperative chemo + radio 1 = postoperative chemo +

radio

2 = preoperative chemo 2 = postoperative chemo

3 = preoperative radio 3 = postoperative radio

4 = no adjuvant therapies 4 = no adjuvant therapies Date of

adjuvant

treatments

commenced

(ddmmyear)

Date of

adjuvant

treatments

concluded

(ddmmyear)

SURGICAL TREATMENT

Date of admission

(ddmmyear)

Date of surgery

(ddmmyear)

Date of discharge

(ddmmyear)

Type of surgery 1 = right hemicolectomy

2 = left hemicolectomy

3 = transverse colectomy

4 = sigmoid colectomy

5 = subtotal or total colectomy

6 = proctocolectomy

7 = abdominoperineal resection/excision

8 = high anterior resection

9 = ultra-low anterior resection

Level of anastomosis

Type of anastomosis 1 = J pouch

2 = straight coloanal anastomosis

Stoma 1= Yes

Appendix 5.2

321

2 = No

Reason for stoma

Date of closure of ostomy

(ddmmyear)

Appendix 5.2

322

PARTICIPANT QUESTIONNAIRE BOOKLET

TIME POINT

Pre-operation (T1)

6 weeks post operation (T2)

6 months post operation (T2/T3)

`

Appendix 5.2

323

BACKGROUND INFORMATION

The information you provide will remain strictly confidential.

1. Which of the following best describes your social situation? (Please tick whichever

applies)

1. Home alone, independent �

2. Home with family �

3. Home with supports �

4. Retirement village �

5. Nursing home – low level care �

6. Nursing home – high level care �

7. Other _______________ �

2. Which of the following best describes your current employment status? (Please tick

whichever applies)

1. Working full time �

2. Working part time or as a casual �

3. Sick leave/ leave of absence – temporary �

4. Sick leave/ leave of absence – permanent �

5. Not employed/ taking time off work �

6. Retired �

7. Home duties �

8. Studying �

9. Other _______________ �

3. What is your marital status? (Please tick whichever applies)

1. single �

2. in a steady relationship �

3. living with partner �

4. married for first time �

5. remarried �

6. separated �

7. divorced �

8. widowed �

9. Other _______________ �

Appendix 5.2

324

4. What is the highest level of formal education that you obtained? (Please tick

whichever applies)

1. No formal schooling �

2. Some primary schooling �

3. Finished primary schooling �

4. Some secondary or high school �

5. Completed secondary or high school �

6. Some trade, community or TAFE college �

7. Completed trade, community, TAFE college �

8. Some university �

9. Completed Bachelor’s degree �

10. Completed Masters or PhD degree �

11. Other ________________________ �

5. How active are you?

0. Fully active �

1. Walking, but only can do light work �

2. Rest in bed LESS than half the day, do not work but

can care for self

�

3. Rest in bed MORE than half the day, and only

partially cares for self �

4. Bedridden �

Appendix 5.2

325

MEDICAL INFORMATION

Please complete the following questions (where relevant) regarding your medical

history. The information you provide will remain strictly confidential.

1. Current medications: (Please tick your current medications if you can, or bring

them with you to your next appointment, we will complete this question for you)

1. Iron or calcium supplements �

2. Diuretics (water pills) �

3. Drugs to reduce bladder urgency (e.g. anticholinergics) �

4. Drugs for depression �

5. Drugs for strong pain (e.g. Narcotic agents) �

6. Drugs for inflammation or mild to moderate pain (e.g. NSAIDs) �

7. Drugs for blood pressure (e.g. Isoptin, Norvasc, Clonidine,

Propanolol) �

8. Psychiatric medicine (e.g. Clozapine) �

9. Drugs for allergy symptoms (e.g. cough/cold medicines,

Promethazine) �

10. Drugs for lung disease (e.g. Clonidine, Salbutamol, Metroprolol) �

11. Antacids containing aluminum or calcium �

12. Drugs for high levels of cholesterol (e.g. Questran Lite, clifibrate) �

13. Drugs provide relief for diarrhoea �

14. Drugs for hear and blood vessel diseases (e.g. methyldopa, digoxin,

quinidine, propanolol, ACE inhibitors)

�

15. Drugs for stomach and bowel diseases (e.g. overuse laxatives,

lactulose, antacids (Mg) H2 antagonists, proton pump inhibitors,

olsalazine, misoprostol)

�

16. Drugs for bones and muscles disease (e.g. colchicine, indomethacin,

auranofin, naproxen, phenylbutazone, mefanamic acid)

�

17. Drugs for brain and spinal cord disease (e.g. anticholinergic agents,

levadopa, alprozolam, lithium, fluxetine, donepezil, amantidine)

�

18. Drugs for diabetes (e.g. oral hypoglycaemic agents) �

19 Drugs for reduced level of thyroid hormone (e.g. thyroxine) �

20. Drugs for infection (e.g. antibiotics, antimetabolites) �

21. Other __________________________ �

Note: If you are male, please skip Questions 2 and 3.

2. Obstetric (females only): (Please tick whichever applies)

Appendix 5.2

326

1. Having given birth two or more times �

2. Age < 25 years at first delivery �

3. Age ≥ 30 years at first delivery �

4. Epidural in labour �

5. Prolonged active 2nd stage (≥ 1hour) �

6. Forceps / ventouse delivery �

7. Large baby ≥ 4.5kg �

8. Third-forth degree sphincter rupture during birth �

9. Single drainage by catheter ≥ 800ml �

10. Shoulder dystocia �

11. Persistent occipito-posterior position �

3. Hormonal status (females only): are you currently

1. Menstruating regularly �

2. Peri-menopausal (time from the onset of menopausal

symptoms [some or all of symptoms such as irregular

periods, hot flushes, night sweats or sleep disturbance]

to the last menstrual period)

�

3. Post menopausal (not experiencing a menstrual bleed

for a minimum of 12 months)

�


Please tick your most appropriate answer, based on your experiences in the last

month.

Note: If you are male, please skip ‘Prolapse Section’ and ‘Sexual Function Section’

Bladder section

Q1 How many times do you pass

urine in the day?

[ ] up to 7

[ ] between 8 – 10

[ ] between 11 – 15

[ ] > 15



[ ] 0 – 1

[ ] 2

[ ] 3

[ ] > 3



[ ] never




Q4 Do you need to rush or hurry

to pass urine when you get the

urge?

[ ] never



[ ] daily


rush or hurry to the toilet? Do you

not make it in time?

[ ] never



[ ] daily


sneezing, laughing or exercising?

[ ] never



[ ] daily



[ ] never



[ ] daily



[ ] never



[ ] daily


empty your bladder?

[ ] never



[ ] daily






bladder infections?

Appendix 5.2

327

[ ] none – never

[ ] as a precaution

[ ] with exercise/during a cold

[ ] daily

leakage?

[ ] never


[ ] moderately

[ ] always

[ ] no

[ ] 1 – 3 per year

[ ] 4 – 12 per year

[ ] > 1 per month



empty your bladder?

[ ] never



[ ] daily


your routine activities (recreation,

socializing, sleeping, shopping

etc.)?

[ ] not at all

[ ] slightly

[ ] moderately

[ ] greatly



[ ] not at all

[ ] slightly

[ ] moderately

[ ] greatly

Bowel Section


open your bowels?





Q 17 What is the consistency of

your usual stool?

[ ] soft

[ ] firm

[ ] hard (pebbles)

[ ] watery

[ ] variable

Q 18 Do you have to strain a lot to

empty your bowels?

[ ] never



[ ] daily


empty your bowels?

[ ] never



[ ] daily


[ ] never



[ ] daily

Q 21 When you get wind or flatus,

can you control it or does wind

leak?

[ ] never



[ ] daily

Q 22 Do you get an

overwhelming sense of urgency


[ ] never



[ ] daily



[ ] never



[ ] daily



[ ] never



[ ] daily



[ ] never



[ ] daily

Q 26 Do you have to use finger

pressure to help empty your

bowels?

[ ] never



[ ] daily

Q 27 How much does your bowel

problem bother you?

[ ] not at all

[ ] slightly

[ ] moderately

[ ] greatly

Prolapse section (females only)

Q 28 Do you have a sensation of

tissue protrusion or a lump or


[ ] never



[ ] daily



dragging sensation?

[ ] never



[ ] daily



your bladder?

[ ] never



[ ] daily



bowels?

[ ] never



[ ] daily



[ ] not at all

[ ] slightly

[ ] moderately

[ ] greatly

Sexual Function Section (females only)

Appendix 5.2

328


[ ] no

[ ] < 1 x week

[ ] 1 x week



please answer Q34 and Q42 only.






[ ] vaginal dryness

[ ] too painful



[ ] other reasons:


natural vaginal lubrication during

intercourse?

[ ] yes

[ ] no


sensation is:


[ ] minimal

[ ] painful

[ ] none


is too loose or lax?

[ ] never

[ ] occasionally

[ ] frequently

[ ] always


is too tight?

[ ] never

[ ] occasionally

[ ] frequently

[ ] always

Q 39 Do you experience pain

with sexual intercourse?

[ ] never

[ ] occasionally

[ ] frequently

[ ] always

Q 40 Where does the pain during

intercourse occur?

[ ] not applicable, I do not have

pain

[ ] at the entrance to the vagina



the pelvis


sexual intercourse?

[ ] never

[ ] occasionally

[ ] frequently

[ ] always



[ ] not at all

[ ] slightly

[ ] moderately

[ ] greatly

Appendix 5.2

329



Many people experience bowel accidents or bowel leakages. We are trying to find out

how many people experience these symptoms and how much this bothers them. We

would be grateful if you could answer the following questions, thinking about how

you have been over the PAST THREE MONTHS.

1 Please write in your

date of birth:

DAY MONTH YEAR

2 Are you (tick

one):

Female Male

Bowel pattern



(a) (b)

Usual At worst

less than once 1

1

one to three times 2 2

three to ten times 3 3

ten or more times 4 4



0 1 2 3 4 5 6 7 8 9 10




(a)

never 0

once 1

twice 2

three times 3

four or more times 4



0 1 2 3 4 5 6 7 8 9 10


Appendix 5.2

330


(Tick one box)

(a)

never 0

rarely 1

some of the time 2

most of the time 3

always 4



0 1 2 3 4 5 6 7 8 9 10




(a)

never 0




about once a day 4

several times a day 5



0 1 2 3 4 5 6 7 8 9 10


Appendix 5.2

331

7

Do you experience pain/soreness around your back passage? (Tick one

box)

(a)

never 0

rarely 1

some of the time 2

most of the time 3

always 4



0 1 2 3 4 5 6 7 8 9 10


Bowel pattern score: sum scores 3a - 7a

Bowel control



(a)

never 0




everyday 4



0 1 2 3 4 5 6 7 8 9 10


Appendix 5.2

332



(a)

always 0

most of the time 1

some of the time 2

rarely 3

never 4



0 1 2 3 4 5 6 7 8 9 10




(a)

always 0

most of the time 1

some of the time 2

rarely 3

never 4



0 1 2 3 4 5 6 7 8 9 10



(Tick one box)

(a)

always 0

most of the time 1

some of the time 2

rarely 3

never 4



0 1 2 3 4 5 6 7 8 9 10


Appendix 5.2

333


passage?

(Tick one box)

(a)

always 0

most of the time 1

some of the time 2

rarely 3

never 4



0 1 2 3 4 5 6 7 8 9 10


13 Do you have bowel accidents when you have no need to open your

bowels?

(Tick one box)

(a)

never 0

rarely 1

some of the time 2

most of the time 3

always 4



0 1 2 3 4 5 6 7 8 9 10



(a)

never 0

rarely 1

some of the time 2

most of the time 3

always 4



0 1 2 3 4 5 6 7 8 9 10


Appendix 5.2

334

Bowel control score: sum scores 8a – 14a


15 Using the pictures please indicate how your bowel movements are most of

the time? (Tick all boxes that apply)

(a)

separate hard lumps like nuts (hard to pass) 1

sausage-shaped but lumpy 2

like a sausage but with cracks on its surface 3

like a sausage or snake – smooth and soft 4

soft blobs with clear cut edges (easy to pass) 5

fluffy pieces with ragged edges, a mushy stool 6

watery, no solid pieces 7



0 1 2 3 4 5 6 7 8 9 10



(a)

never 0

rarely 1

some of the time 2

most of the time 3

always 4



0 1 2 3 4 5 6 7 8 9 10


Appendix 5.2

335

17 Is the possibility of having a bowel accident on your mind? (Tick one

box)

(a)

never 0

rarely 1

some of the time 2

most of the time 3

always 4



0 1 2 3 4 5 6 7 8 9 10


Sexual impact


box)

(a)

never 0

rarely 1

some of the time 2

most of the time 3

always 4

not applicable 5



0 1 2 3 4 5 6 7 8 9 10


Quality of life


(a)

never 0

rarely 1

some of the time 2

most of the time 3

always 4



0 1 2 3 4 5 6 7 8 9 10


Appendix 5.2

336


(Tick one box)

(a)

never 0

rarely 1

some of the time 2

most of the time 3

always 4



0 1 2 3 4 5 6 7 8 9 10



(Tick one box)

(a)

never 0

rarely 1

some of the time 2

most of the time 3

always 4



0 1 2 3 4 5 6 7 8 9 10



(Tick one box)

(a)

never 0

rarely 1

some of the time 2

most of the time 3

always 4



0 1 2 3 4 5 6 7 8 9 10


Appendix 5.2

337



0 1 2 3 4 5 6 7 8 9 10


Quality of life score: sum scores 19a -23

24

Please use the space below to describe any worries you have about bowel

accidents or leakages, what you think may have caused your bowel

accidents or leakages, or anything else you think we should know.

Thank you very much for answering these questions.

Appendix 5.2

338

ICIQ-UI SF

Many people leak urine some of the time. We are trying to find out how many people

leak urine, and how much this bothers them. We would be grateful if you could

answer the following questions, thinking about how you have been, on average, over

the PAST FOUR WEEKS.

1 How often do you leak urine? (Tick one box)

never

about once a week or less often

two or three times a week

about once a day

several times a day

all the time

2 We would like to know how much urine you think leaks.

How much urine do you usually leak (whether you wear protection or

not)?

(Tick one box)

none

a small amount

a moderate amount

a large amount

3 Overall, how much does leaking urine interfere with your everyday life?


0 1 2 3 4 5 6 7 8 9 10


4 When does urine leak? (Please tick all that apply to you)

never – urine does not leak

leaks before you can get to the toilet leaks when you cough or sneeze leaks when you are asleep leaks when you are physically active/exercising leaks when you have finished urinating and are dressed leaks for no obvious reason

leaks all the time

Thank you very much for answering these questions.

Appendix 5.2

339

INTERNATIONAL PHYSICAL ACTIVITY QUESTIONNAIRE

We are interested in finding out about the kinds of physical activities that people do as

part of their everyday lives. The questions will ask you about the time you spent

being physically active in the last 7 days. Please answer each question even if you

do not consider yourself to be an active person. Please think about the activities you

do at work, as part of your house and yard work, to get from place to place, and in

your spare time for recreation, exercise or sport.

Think about all the vigorous activities that you did in the last 7 days. Vigorous

physical activities refer to activities that take hard physical effort and make you

breathe much harder than normal. Think only about those physical activities that

you did for at least 10 minutes at a time.

1. During the last 7 days, on how many days did you do vigorous physical

activities like heavy lifting, digging, aerobics, or fast bicycling?

_____ days per week

No vigorous physical activities Skip to question 3

2. How much time did you usually spend doing vigorous physical activities on

one of those days?

_____ hours per day

_____ minutes per day

Don’t know/Not sure

Think about all the moderate activities that you did in the last 7 days. Moderate

activities refer to activities that take moderate physical effort and make you breathe

somewhat harder than normal. Think only about those physical activities that you

did for at least 10 minutes at a time.

3. During the last 7 days, on how many days did you do moderate physical

activities like carrying light loads, bicycling at a regular pace, or doubles

tennis? Do not include walking.

_____ days per week

No moderate physical activities Skip to question 5

4. How much time did you usually spend doing moderate physical activities on

one of those days?

_____ hours per day



Appendix 5.2

340

Think about the time you spent walking in the last 7 days. This includes at work

and at home, walking to travel from place to place, and any other walking that you

have done solely for recreation, sport, exercise, or leisure.

5. During the last 7 days, on how many days did you walk for at least 10

minutes at a time?

_____ days per week

No walking Skip to question 7

6. How much time did you usually spend walking on one of those days?

_____ hours per day



The last question is about the time you spent sitting on weekdays during the last 7

days. Include time spent at work, at home, while doing course work and during

leisure time. This may include time spent sitting at a desk, visiting friends, reading,

or sitting or lying down to watch television.

7. During the last 7 days, how much time did you spend sitting on a week day?

_____ hours per day



Appendix 5.2

341

Hospital Anxiety and Depression Scale

This questionnaire is designed to help us to know how you have been feeling. Read each item

below. Circle the number that best describes how you have been feeling in the past week. Do

not take too long over your replies. Your immediate reaction to each item will probably be

more accurate than a long, thought-out response.

A

I feel tense or 'wound up':

Most of the time 3

A lot of the time 2

From time to time, occasionally 1

Not at all 0

D

I still enjoy the things I used to enjoy:

Definitely as much 0

Not quite so much 1

Only a little 2

Hardly at all 3

A

I get a sort of frightened feeling as if something awful is about to

happen:

Very definitely and quite badly 3

Yes, but not too badly 2

A little, but it doesn't worry me 1

Not at all 0

D

I can laugh and see the funny side of things:

As much as I always could 0

Not quite so much now 1

Definitely not so much now 2

Not at all 3

A

Worrying thoughts go through my mind:

A great deal of the time 3

A lot of the time 2

From time to time, but not too often 1

Only occasionally 0

D

I feel cheerful:

Not at all 3

Not often 2

Sometimes 1

Most of the time 0

Appendix 5.2

342

A

I can sit at ease and feel relaxed:

Definitely 0

Usually 1

Not Often 2

Not at all 3

D

I feel as if I am slowed down:

Nearly all the time 3

Very often 2

Sometimes 1

Not at all 0

A

I get a sort of frightened feeling like 'butterflies' in the stomach:

Not at all 0

Occasionally 1

Quite Often 2

Very Often 3

D

I have lost interest in my appearance:

Definitely 3

I don't take as much care as I should 2

I may not take quite as much care 1

I take just as much care as ever 0

A

I feel restless as I have to be on the move:

Very much indeed 3

Quite a lot 2

Not very much 1

Not at all 0

D

I look forward with enjoyment to things:

As much as I ever did 0

Rather less than I used to 1

Definitely less than I used to 2

Hardly at all 3

A

I get sudden feelings of panic:

Very often indeed 3

Quite often 2

Not very often 1

Not at all 0

D

I can enjoy a good book or radio or TV program:

Often 0

Sometimes 1

Not often 2

Very seldom 3

Appendix 5.2

343

EORTC QLQ-C30 (VERSION 3)

We are interested in some things about you and your health. Please answer all of the

questions yourself by circling the number that best applies to you. There are no "right" or "wrong" answers. The information that you provide will remain strictly

confidential.

Not at A Quite Very

All Little a Bit Much 1. Do you have any trouble doing strenuous activities,

like carrying a heavy shopping bag or a suitcase? 1 2 3 4

2. Do you have any trouble taking a long walk? 1 2 3 4

3. Do you have any trouble taking a short walk outside of the

house? 1 2 3 4

4. Do you need to stay in bed or a chair during the day? 1 2 3 4

5. Do you need help with eating, dressing, washing yourself or using the toilet? 1 2 3 4

During the past week: Not at A Quite Very All Little a Bit Much 6. Were you limited in doing either your work or other daily

activities? 1 2 3 4 7. Were you limited in pursuing your hobbies or other

leisure time activities?

1

2

3 4

8. Were you short of breath?

1

2

3 4

9. Have you had pain?

1

2

3 4

10. Did you need to rest?

1

2

3 4

11. Have you had trouble sleeping?

1

2

3 4

12. Have you felt weak?

1

2

3 4

13. Have you lacked appetite?

1

2

3 4

14. Have you felt nauseated?

1

2

3 4

15. Have you vomited?

1

2

3 4

16. Have you been constipated?

1

2

3 4

Appendix 5.2

344

During the past week: Not at A Quite Very All Little a Bit Much

17. Have you had diarrhoea? 1 2 3 4

18. Were you tired? 1 2 3 4

19. Did pain interfere with your daily activities? 1 2 3 4

20. Have you had difficulty in concentrating on things, like reading a newspaper or watching television? 1 2 3 4

21. Did you feel tense? 1 2 3 4

22. Did you worry? 1 2 3 4

23. Did you feel irritable? 1 2 3 4

24. Did you feel depressed? 1 2 3 4

25. Have you had difficulty remembering things? 1 2 3 4

26. Has your physical condition or medical treatment interfered with your family life? 1 2 3 4

27. Has your physical condition or medical treatment interfered with your social activities? 1 2 3 4

28. Has your physical condition or medical treatment caused you financial difficulties? 1 2 3 4

For the following questions please circle the

number between 1 and 7 that

best applies to you

29. How would you rate your overall health during the past week?

1 2 3 4 5 6 7

Very poor Excellent

30. How would you rate your overall quality of life during the past week?

1 2 3 4 5 6 7

Very poor Excellent © Copyright 1995 EORTC Quality of Life Group. All rights reserved. Version 3.0

Appendix 5.2

345

EORTC QLQ-CR 29

Patients sometimes report that they have the following symptoms or problems. Please

indicate the extent to which you have experienced these symptoms or problems during

the past week. Please answer by circling the number that best applies to you.


at

All

A

Little Quite

a Bit Very

Much

31. Did you urinate frequently during the day? 1 2 3 4

32. Did you urinate frequently during the night? 1 2 3 4

33. Have you had any unintentional release (leakage) of urine? 1 2 3 4

34. Did you have pain when you urinated? 1 2 3 4

35. Did you have abdominal pain? 1 2 3 4

36. Did you have pain in your buttocks/anal area/rectum? 1 2 3 4

37. Did you have a bloated feeling in your abdomen? 1 2 3 4

38. Have you had blood in your stools? 1 2 3 4

39. Have you had mucus in your stools? 1 2 3 4

40. Did you have a dry mouth? 1 2 3 4

41. Have you lost hair as a result of your treatment? 1 2 3 4

42. Have you had problems with your sense of taste? 1 2 3 4


All A

Little Quite

a Bit Very

Much

43. Were you worried about your health in the

future? 1 2 3 4

44. Have you worried about your weight? 1 2 3 4

45. Have you felt physically less attractive as a

result of your disease or treatment?

1

2

3

4

46. Have you been feeling less feminine/masculine as a


1

2

3

4

47. Have you been dissatisfied with your body? 1 2 3 4

48. Do you have a stoma bag

(colostomy/ileostomy)? (please circle the correct

answer)

Yes

No

Please go on to the next page

Appendix 5.2

346


All A

Little Quite

a Bit

Very

Much

Answer these questions ONLY IF YOU HAVE A STOMA BAG, if not please continue

below:

49. Have you had unintentional release of gas/flatulence from your stoma bag? 1 2 3 4

50. Have you had leakage of stools from your stoma bag? 1 2 3 4

51. Have you had sore skin around your stoma? 1 2 3 4

52. Did frequent bag changes occur during the day? 1 2 3 4

53. Did frequent bag changes occur during the night? 1 2 3 4

54. Did you feel embarrassed because of your stoma? 1 2 3 4

55. Did you have problems caring for your stoma? 1 2 3 4


49. Have you had unintentional release of gas/flatulence

from your back passage?

1

2

3

4

50. Have you had leakage of stools from your back

passage? 1 2 3 4

51. Have you had sore skin around your anal area? 1 2 3 4

52. Did frequent bowel movements occur during the day? 1 2 3 4

53. Did frequent bowel movements occur during the

night? 1 2 3 4

54. Did you feel embarrassed because of your bowel

movement? 1 2 3 4

During the past 4 weeks:

Not

at

All

A

Little

Quite

a Bit

Very

Much

For men only:

56. To what extent were you interested in sex? 1 2 3 4

57. Did you have difficulty getting or maintaining an erection? 1 2 3 4

For women only:

58. To what extent were you interested in sex? 1 2 3 4

59. Did you have pain or discomfort during intercourse? 1 2 3 4

This is the end of the questionnaire, thank you for participating.

Appendix 6.1

347


Appendix 6.1

348

Appendix 6.1

349

Appendix 6.2

350

Appendix 6.2 “Exercise for home” sheet (Study 4)

Exercises for Home Description of Exercise Picture

1. BICEP CURLS

Sitting on a stool/chair or

fitball, place the theraband

underneath your feet and hold

in your hands.

Keep your band tight enough

to create resistance when you

pull it.

Keep elbows close to your

side.

Bent at the elbow bringing

your hands closer to your

shoulder. Whilst doing this

contract your pelvic floor

muscles, think about pulling

them up away from the seat.

Then slowly lower the band

and your hands towards your

leg. Relax your pelvic floor

completely.

2. CHARIOT PULLS

In the same starting position

as bicep curls above. Arms

stay straight at the elbow.

Gently pull arms past hips, at

the same time try and contract

your pelvic floor muscles.

Then slowly release your

arms and pelvic floor.

As you pull the band gently

draw your belly button

towards your spine. Sit tall.

Appendix 6.2

351

3. SHOULDER

STABILITY

Sitting on the ball/stool or

standing if preferred.

Band is in hands at short

distance (approx 5cm).

Elbows bent to right angle

and tucked in at side.

Palms facing each other.

Pull the band by pulling hands

away from each other, keep

elbows still. Gently release.

Description of Exercise Picture 4. FORWARD RAISE

Sitting on fitball/stool. Place

band around back at bra level

and then hold each side in

each hand at the front.

Pull band out and forwards

from chest level.

Gently and slowly release.

Keep drawing in your lower

tummy muscles to engage

your core and also think about

engaging your pelvic floor.

Appendix 6.2

352

5. LEG TO BACK

Tie band around sturdy table

leg or pole. Loop band around

ankle. Gentle pull leg straight

back, moving from the hip,

not the knee.

The slowly release leg back to

start position.

6. LEG TO SIDE

Same as 5. This time stand

side on to pole/band

attachment point.

Gently pull leg to the side,

keeping toes pointing to the

front. Then slowly release

back to starting position.

7. SQUATS

Standing with your feet hip

width apart, engage your

pelvic floor muscles as you

squat down as if sitting on a

chair. Ensure your knees

don’t cover your toes as you

go down, make sure you can

see your toes! Then slowly

come back up to standing and

then relax your pelvic floor

muscles.

You can also do this against

the wall with a fitball in the

small of your back.

Appendix 6.2

353

8. HEEL RAISES

Standing with your feet hip

width apart, lift your heels up

off the ground then slowly

lower. If you want to advance

this exercise try it on one leg.

Use a chair in-front or wall

for balance.

Think about staying tall and

not letting your heels fall

towards the floor, lower

gradually.

Appendix 6.3

354

Appendix 6.3 Exercise diary (Study 4)

WEEK 1 Example Date (aim for 5

sessions per week

of cardiovascular

exercise and 2 of

strengthening)

30/3/15 WEEKLY

STATS

Office

Use

No. of steps (aim

for 10,000)

10,000 steps

Exercise type

(Cardio)

e.g.

Cycle/walk/swim

Walk

N/A

Time spent

exercising(minutes)

(aim for 150

minutes per week)

60mins

mins

Intensity of

Cardio (see back

page for BORG

Scale– aim for 13)

13

N/A

Strengthening

exercises (eg.

Theraband,

weights) Yes/No

(aim for 2 sessions

per week)

*Theraband

program handout

can be used

Yes

No of

sessions

achieved:

0 / 1 / 2

WEEK 2

Date WEEKLY

STATS

Office

Use

No. of steps steps

Exercise type

(Cardio)

N/A

Time spent

exercising(minutes)

mins

Intensity of

Cardio (see back

page for BORG

Scale)

N/A

Strengthening

exercises (e.g.

Theraband,

weights) Yes/No

No of

sessions

achieved:

0 / 1 / 2

Appendix 6.3

355

WEEK 3

Date WEEKLY

STATS

Office

Use

No. of steps steps

Exercise type

(Cardio)

N/A

Time spent

exercising(minutes)

mins

Intensity of

Cardio (see back

page for BORG

Scale)

N/A

Strengthening

exercises (e.g.

Theraband,

weights) Yes/No

No of

sessions

achieved:

0 / 1 / 2

WEEK 4

Date WEEKLY

STATS

Office

Use

No. of steps steps

Exercise type

(Cardio)

N/A

Time spent

exercising(minutes)

mins

Intensity of

Cardio (see back

page for BORG

Scale)

N/A

Strengthening

exercises (e.g.

Theraband,

weights) Yes/No

No of

sessions

achieved:

0 / 1 / 2

WEEK 5

Date WEEKLY

STATS

Office

Use

No. of steps steps

Exercise type

(Cardio)

N/A

Time spent

exercising(minutes)

mins

Intensity of

Cardio (see back

page for BORG

Scale)

N/A

Strengthening

exercises (e.g.

Theraband,

weights) Yes/No

No of

sessions

achieved:

0 / 1 / 2

Appendix 6.3

356

WEEK 6

Date WEEKLY

STATS

Office

Use

No. of steps steps

Exercise type

(Cardio)

N/A

Time spent

exercising(minutes)

mins

Intensity of

Cardio (see back

page for BORG

Scale)

N/A

Strengthening

exercises (e.g.

Theraband,

weights) Yes/No

No of

sessions

achieved:

0 / 1 / 2

WEEK 7

Date WEEKLY

STATS

Office

Use

No. of steps steps

Exercise type

(Cardio)

N/A

Time spent

exercising(minutes)

mins

Intensity of

Cardio (see back

page for BORG

Scale)

N/A

Strengthening

exercises (e.g.

Theraband,

weights) Yes/No

No of

sessions

achieved:

0 / 1 / 2

WEEK 8

Date WEEKLY

STATS

Office

Use

No. of steps steps

Exercise type

(Cardio)

N/A

Time spent

exercising(minutes)

mins

Intensity of

Cardio (see back

page for BORG

Scale)

N/A

Strengthening

exercises (e.g.

Theraband,

weights) Yes/No

No of

sessions

achieved:

0 / 1 / 2

Appendix 6.3

357

BORG Scale

Appendix 6.4

358

Appendix 6.4 Data Collection Sheets (Study 4)

DEMOGRAPHICS

(Please circle number or tick box)

DEMOGRAPHICS

Date of birth

(ddmmyear)

Age (year)

Gender 1 = Male 2 = Female

Height (cm)

Weight (kg) T1 T2 T3

Smoking status 1 = Never smoked 2 = Ex smoker 3 = Current smoker

Number of years

smoked

Number of packets/day

MEDICAL HISTORY

Medical conditions Charlson Comorbidity Index

assigned weights

� Myocardial Infarction 1

� Congestive heart failure

� Peripheral vascular disease

� Cerebrovascular disease

� Dementia

� Chronic obstructive pulmonary disease

� Connective tissue disease

� Peptic ulcer disease

� Mild liver disease

� Diabetes

� Hemiplegia 2

� Moderately severe renal disease

� Diabetes with end-organ damage

� Any tumour (within last 5 years)

� Lymphoma

� Leukaemia

� Moderately severe liver disease 3

� Metastatic solid tumour 6

� AIDS

ONCOLOGY

Histology T1 T2 T3

Stage of cancer 1 = Stage I 1 1

2 = Stage IA 2 2

3 = Stage IA1 3 3

4 = Stage IA2 4 4

5 = Stage IB 5 5

6 = Stage IB1 6 6

7 = Stage IB2 7 7

8 = Stage II 8 8

9 = Stage IIA 9 9

10 = Stage IIA1 10 10

11 = Stage IIA2 11 11

Appendix 6.4

359

12 = Stage IIB 12 12

13 = Stage IIC 13 13

14 = Stage III 14 14

15 = Stage IIIA 15 15

16 = Stage IIIB 16 16

17 = Stage IIIC 17 17

18 = Metastases 18 18

19 = Recurrent cancer 19 19

Level of tumour � 1 Colon � 2 Rectum � 3 Prostate � 4 Bladder

� 5 Uterus � 6 Ovary � 7 Cervix � 8 Fallopian tube � 9

Placenta

Adjuvant

treatments

1 = preoperative chemo + radio

2 = preoperative chemo

3 = preoperative radio

4 = postoperative chemo + radio

5 = postoperative chemo

6 = postoperative radio

7= no adjuvant therapies Date of adjuvant

treatments

commenced

(ddmmyear)

Date of adjuvant

treatments

concluded

(ddmmyear)

SURGICAL TREATMENT

Date of admission

(ddmmyear)

Date of surgery (ddmmyear)

Date of discharge

(ddmmyear)

Type of surgery 1 = right hemicolectomy

2 = left hemicolectomy

3 = transverse colectomy

4 = sigmoid colectomy

5 = subtotal or total colectomy

6 = proctocolectomy

7 = abdominoperineal resection/excision

8 = high anterior resection

9 = ultra-low anterior resection

10 = hysterectomy

11 = laparotomy

12 = Salpingo-oophorectomy

13 = radical prostatectomy

14 = nephrectomy

15 = orchidectomy

16 = total excision of bladder

Appendix 6.4

360

SIX MINUTE WALK TEST RECORDING SHEET

Time Point (please tick the box):

Baseline (T1)

Immediately post-Physiotherapy intervention (T2)

Follow up at 6 months after baseline (T3)

Walk 1 Walk 2

Time:___________ Time:___________

Weight

_____kg

Height

______cm

Waist circumference

_______cm

Time

(mins)

Dyspnoea

(Borg)

Leg

fatigue

(Borg)

HR SpO2 Time

(mins)

Dyspnoea

(Borg)

Leg

fatigue

(Borg)

HR SpO2

Rest Rest

1 1

2 2

3 3

4 4

5

5

6

6

Recovery

1

Recovery

1

Distance (m):________________ Distance (m):_____________


1. SOB 1. SOB

2. Leg fatigue 2. Leg fatigue

3. Other: _______________ 3. Other:_______________

Appendix 6.4

361

HAND-GRIP STRENGTH RECORDING SHEETS


Baseline (T1)

Immediately post-Physiotherapy intervention (T2)

Follow up at 6 months after baseline (T3)

Dominant Hand

Right Left

HAND-GRIP STRENGTH

RIGHT LEFT

1

(kg)

2

(kg)

3

(kg)

1

(kg)

2

(kg)

3

(kg)

Appendix 6.4

362

FOR OFFICE USE ONLY ID number:

Date:

Oncology Rehabilitation Research Project

for patients following surgery for pelvic cancer

PARTICIPANT QUESTIONNAIRE

BOOKLET (colorectal cancer)

We would be very grateful if you could complete and bring this questionnaire

booklet with you to your appointment.

Thank you for taking the time to help us with our research.

Appendix 6.4

363

Please start here

Date questionnaire filled in (dd/mm/yyyy): _ _ / _ _ / 2 0 1 _

Your date of birth (dd/mm/yyyy): _ _ / _ _ / 1 9 _ _

Sex: [ ] Male [ ] Female

BACKGROUND INFORMATION

The information you provide will remain strictly confidential.

1. Which of the following best describes your social situation? (Please tick whichever

applies)

1. Home alone, independent �

2. Home with family �

3. Home with supports �

4. Retirement village �

5. Nursing home – low level care �

6. Nursing home – high level care �

7. Other (please specify)_______________ �

2. Which of the following best describes your current employment status? (Please tick

whichever applies)

1. Working full time �

2. Working part time or as a casual �

3. Sick leave/ leave of absence – temporary �

4. Sick leave/ leave of absence – permanent �

5. Not employed/ taking time off work �

6. Retired �

7. Home duties �

8. Studying �

9. Other (please specify)_______________ �

Appendix 6.4

364

3. What is your marital status? (Please tick whichever applies)

1. single �

2. in a steady relationship �

3. living with partner �

4. married for first time �

5. remarried �

6. separated �

7. divorced �

8. widowed �

9. Other (please specify) _______________ �

4. What is the highest level of formal education that you have obtained? (Please tick

whichever applies)

1. No formal schooling �

2. Some primary schooling �

3. Finished primary schooling �

4. Some secondary or high school �

5. Completed secondary or high school �

6. Some trade, community or TAFE college �

7. Completed trade, community, TAFE college �

8. Some university �

9. Completed Bachelor’s degree �

10. Completed Masters or PhD degree �

11. Other (please specify)____________________ �

Appendix 6.4

365

MEDICAL INFORMATION

Please complete the following questions (where relevant) regarding your medical

history. The information you provide will remain strictly confidential.

1. Current medications: (Please list your current medications if you can, or bring them

with you to your appointment so that we can assist you to complete this question)

Medication Dosage

2. Surgical history: (Please tick, circle details and enter dates where applicable)

Past surgical history Date (ddmmyear)

1. bladder surgery (e.g. colposuspension / sling etc)

2. gynaecological surgery (e.g. hysterectomy /

prolapse repair)

3. bowel surgery (e.g. rectal prolapse / bowel

incontinence)

4. anal surgery (e.g. haemorrhoids / anal fissures

repair)

5. kidney surgery

6. back surgery

7. other surgery (please specify)

_______________________________________

Note: If you are male, please skip Questions 3 and 4.

Appendix 6.4

366

3. Birth history (females only): (Please tick and answer whichever applies)

If you have not given birth before, please tick here □ and go to question 3

1. Have given birth:

How many times? _______________ �

2. A history of bladder or bowel problems before your first

baby was born �

3. Age ≥ 35 years at first childbirth �

4. Epidural in any labor �

5. Prolonged (≥ 1hour) 2nd stage of labour (any labour) �

6. Forceps / ventouse (vacuum extraction) childbirth (any

childbirth) �

7. Large baby ≥ 4kg (any baby) �

8. Severe tear (third or fourth degree tear) during birth (any

birth) �

4. Hormonal status (females only): are you currently

1. Menstruating regularly �

2. Peri-menopausal (time from the onset of menopausal

symptoms [some or all of symptoms such as irregular

periods, hot flushes, night sweats or sleep disturbance]

to the last menstrual period)

�

3. Post menopausal (not experienced a menstrual bleed

for a minimum of 12 months)

�

Appendix 6.4

367


Please tick your most appropriate answer, based on your experiences in the last

month.

Note: If you are male, please skip ‘Prolapse Section’ and ‘Sexual Function Section’

Bladder Section

Q1 How many times do you

pass urine in the day?

[ ] up to 7

[ ] between 8 – 10

[ ] between 11 – 15

[ ] > 15



[ ] 0 – 1

[ ] 2

[ ] 3

[ ] > 3



[ ] never




Q4 Do you need to rush or

hurry to pass urine when you get

the urge?

[ ] never



[ ] daily


rush or hurry to the toilet? Do

you not make it in time?

[ ] never



[ ] daily


sneezing, laughing or

exercising?

[ ] never



[ ] daily



[ ] never



[ ] daily



[ ] never



[ ] daily


empty your bladder?

[ ] never



[ ] daily



[ ] none – never

[ ] as a precaution

[ ] with exercise/during a

cold

[ ] daily



leakage?

[ ] never


[ ] moderately

[ ] always


bladder infections?

[ ] no

[ ] 1 – 3 per year

[ ] 4 – 12 per year

[ ] > 1 per month



empty your bladder?

[ ] never



[ ] daily


your routine activities

(recreation, socializing,

sleeping, shopping etc.)?

[ ] not at all

[ ] slightly

[ ] moderately

[ ] greatly



[ ] not at all

[ ] slightly

[ ] moderately

[ ] greatly

Bowel Section


open your bowels?





Q 17 What is the consistency

of your usual stool?

[ ] soft

[ ] firm

[ ] hard (pebbles)

[ ] watery

[ ] variable

Q 18 Do you have to strain a lot


[ ] never



[ ] daily


empty your bowels?

[ ] never



[ ] daily


[ ] never

[ ] occasionally (< 1 x

week)


[ ] daily

Q 21 When you get wind or

flatus, can you control it or does

wind leak?

[ ] never



[ ] daily

Appendix 6.4

368

Q 22 Do you get an

overwhelming sense of urgency to

empty your bowels?

[ ] never



[ ] daily



[ ] never


week)


[ ] daily



[ ] never



[ ] daily



[ ] never



[ ] daily

Q 26 Do you have to use

finger pressure to help empty

your bowels?

[ ] never


week)


[ ] daily


bowel problem bother you?

[ ] not at all

[ ] slightly

[ ] moderately

[ ] greatly

Prolapse Section (females only)

Q 28 Do you have a sensation

of tissue protrusion or a lump or


[ ] never



[ ] daily



dragging sensation?

[ ] never



[ ] daily



your bladder?

[ ] never



[ ] daily



bowels?

[ ] never



[ ] daily



[ ] not at all

[ ] slightly

[ ] moderately

[ ] greatly

Sexual Function Section (females only)


[ ] no

[ ] < 1 x week

[ ] 1 x week



please answer Q34 and Q42

only.






[ ] vaginal dryness

[ ] too painful



[ ] other reasons:


natural vaginal lubrication

during intercourse?

[ ] yes

[ ] no


sensation is:


[ ] minimal

[ ] painful

[ ] none


vagina is too loose or lax?

[ ] never

[ ] occasionally

[ ] frequently

[ ] always


vagina is too tight?

[ ] never

[ ] occasionally

[ ] frequently

[ ] always

Q 39 Do you experience pain

with sexual intercourse?

[ ] never

[ ] occasionally

[ ] frequently

[ ] always

Q 40 Where does the pain

during intercourse occur?

[ ] not applicable, I do not

have pain

[ ] at the entrance to the

vagina



sexual intercourse?

[ ] never

[ ] occasionally

[ ] frequently

[ ] always

Appendix 6.4

369


the pelvis



[ ] not at all

[ ] slightly

[ ] moderately

[ ] greatly

Appendix 6.4

370



Many people experience bowel accidents or bowel leakages. We are trying to find out how

many people experience these symptoms and how much this bothers them. We would be

grateful if you could answer the following questions, thinking about how you have been over

the PAST THREE MONTHS.

Bowel pattern



(a) (b)

Usual At worst

less than once

one to three times

three to ten times

ten or more times



0 1 2 3 4 5 6 7 8 9 10




(a)

never

once

twice

three times

four or more times



0 1 2 3 4 5 6 7 8 9 10


Appendix 6.4

371


(Tick one box)

(a)

never

rarely

some of the time

most of the time

always



0 1 2 3 4 5 6 7 8 9 10




(a)

never

less than once a month

less than once a week

less than once a day

about once a day

several times a day



0 1 2 3 4 5 6 7 8 9 10


7

Do you experience pain/soreness around your back passage? (Tick one

box)

(a)

never

rarely

some of the time

most of the time

always



0 1 2 3 4 5 6 7 8 9 10


Appendix 6.4

372

Bowel control



(a)

never

less than once a month

less than once a week

less than once a day

everyday



0 1 2 3 4 5 6 7 8 9 10




(a)

always

most of the time

some of the time

rarely

never



0 1 2 3 4 5 6 7 8 9 10




(a)

always

most of the time

some of the time

rarely

never



0 1 2 3 4 5 6 7 8 9 10


Appendix 6.4

373


(Tick one box)

(a)

always

most of the time

some of the time

rarely

never



0 1 2 3 4 5 6 7 8 9 10



passage?

(Tick one box)

(a)

always

most of the time

some of the time

rarely

never



0 1 2 3 4 5 6 7 8 9 10


13 Do you have bowel accidents when you have no need to open your

bowels?

(Tick one box)

(a)

never

rarely

some of the time

most of the time

always



0 1 2 3 4 5 6 7 8 9 10


Appendix 6.4

374


(a)

never

rarely

some of the time

most of the time

always



0 1 2 3 4 5 6 7 8 9 10



15 Using the pictures please indicate how your bowel movements are most of

the time? (Tick all boxes that apply)

(a)

separate hard lumps like nuts (hard to pass)

sausage-shaped but lumpy

like a sausage but with cracks on its surface

like a sausage or snake – smooth and soft

soft blobs with clear cut edges (easy to pass)

fluffy pieces with ragged edges, a mushy stool

watery, no solid pieces



0 1 2 3 4 5 6 7 8 9 10


Appendix 6.4

375


(a)

never

rarely

some of the time

most of the time

always



0 1 2 3 4 5 6 7 8 9 10


17 Is the possibility of having a bowel accident on your mind? (Tick one box)

(a)

never

rarely

some of the time

most of the time

always



0 1 2 3 4 5 6 7 8 9 10


Sexual impact


box)

(a)

never

rarely

some of the time

most of the time

always

not applicable



0 1 2 3 4 5 6 7 8 9 10


Appendix 6.4

376

Quality of life


(a)

never

rarely

some of the time

most of the time

always



0 1 2 3 4 5 6 7 8 9 10



(Tick one box)

(a)

never

rarely

some of the time

most of the time

always



0 1 2 3 4 5 6 7 8 9 10



(Tick one box)

(a)

never

rarely

some of the time

most of the time

always



0 1 2 3 4 5 6 7 8 9 10


Appendix 6.4

377


(Tick one box)

(a)

never

rarely

some of the time

most of the time

always



0 1 2 3 4 5 6 7 8 9 10




0 1 2 3 4 5 6 7 8 9 10


24

Please use the space below to describe any worries you have about bowel

accidents or leakages, what you think may have caused your bowel

accidents or leakages, or anything else you think we should know.

Appendix 6.4

378

International Consultation on Incontinence Questionnaire - Urinary

Many people leak urine some of the time. We are trying to find out how many people leak

urine, and how much this bothers them. We would be grateful if you could answer the

following questions, thinking about how you have been, on average, over the PAST FOUR

WEEKS.

1 How often do you leak urine? (Tick one box)

never

about once a week or less often

two or three times a week

about once a day

several times a day

all the time

2 We would like to know how much urine you think leaks.

How much urine do you usually leak (whether you wear protection or

not)?

(Tick one box)

none

a small amount

a moderate amount

a large amount

3 Overall, how much does leaking urine interfere with your everyday life?


0 1 2 3 4 5 6 7 8 9 10


4 When does urine leak? (Please tick all that apply to you)

never – urine does not leak

leaks before you can get to the toilet leaks when you cough or sneeze leaks when you are asleep leaks when you are physically active/exercising leaks when you have finished urinating and are dressed leaks for no obvious reason

leaks all the time

Appendix 6.4

379

INTERNATIONAL PHYSICAL ACTIVITY QUESTIONNAIRE We are interested in finding out about the kinds of physical activities that people do as part of their

everyday lives. The questions will ask you about the time you spent being physically active in the

last 7 days. Please answer each question even if you do not consider yourself to be an active person.

Please think about the activities you do at work, as part of your house and yard work, to get from place

to place, and in your spare time for recreation, exercise or sport.

Think about all the vigorous activities that you did in the last 7 days. Vigorous

physical activities refer to activities that take hard physical effort and make you

breathe much harder than normal. Think only about those physical activities that

you did for at least 10 minutes at a time.

1. During the last 7 days, on how many days did you do vigorous physical

activities like heavy lifting, digging, aerobics, or fast bicycling?

_____ days per week

No vigorous physical activities Skip to question 3

2. How much time did you usually spend doing vigorous physical activities on

one of those days?

_____ hours per day



Think about all the moderate activities that you did in the last 7 days. Moderate

activities refer to activities that take moderate physical effort and make you breathe

somewhat harder than normal. Think only about those physical activities that you

did for at least 10 minutes at a time.

3. During the last 7 days, on how many days did you do moderate physical

activities like carrying light loads, bicycling at a regular pace, or doubles

tennis? Do not include walking.

_____ days per week

No moderate physical activities Skip to question 5

4. How much time did you usually spend doing moderate physical activities on

one of those days?

_____ hours per day



Appendix 6.4

380

Think about the time you spent walking in the last 7 days. This includes at work

and at home, walking to travel from place to place, and any other walking that you

have done solely for recreation, sport, exercise, or leisure.

5. During the last 7 days, on how many days did you walk for at least 10

minutes at a time?

_____ days per week

No walking Skip to question 7

8. How much time did you usually spend walking on one of those days?

_____ hours per day



The last question is about the time you spent sitting on weekdays during the last 7

days. Include time spent at work, at home, while doing course work and during

leisure time. This may include time spent sitting at a desk, visiting friends, reading,

or sitting or lying down to watch television.

9. During the last 7 days, how much time did you spend sitting on a week day?

_____ hours per day



Appendix 6.4

381

Hospital Anxiety and Depression Scale

This questionnaire is designed to help us to know how you have been feeling. Read

each item below. Circle the number that best describes how you have been feeling in

the past week. Do not take too long over your replies. Your immediate reaction to

each item will probably be more accurate than a long, thought-out response.

A

I feel tense or 'wound up':

Most of the time 3

A lot of the time 2

From time to time, occasionally 1

Not at all 0

D

I still enjoy the things I used to enjoy:

Definitely as much 0

Not quite so much 1

Only a little 2

Hardly at all 3

A

I get a sort of frightened feeling as if something awful is about to

happen:

Very definitely and quite badly 3

Yes, but not too badly 2

A little, but it doesn't worry me 1

Not at all 0

D

I can laugh and see the funny side of things:

As much as I always could 0

Not quite so much now 1

Definitely not so much now 2

Not at all 3

A

Worrying thoughts go through my mind:

A great deal of the time 3

A lot of the time 2

From time to time, but not too often 1

Only occasionally 0

D

I feel cheerful:

Not at all 3

Not often 2

Sometimes 1

Most of the time 0

Appendix 6.4

382

A

I can sit at ease and feel relaxed:

Definitely 0

Usually 1

Not Often 2

Not at all 3

D

I feel as if I am slowed down:

Nearly all the time 3

Very often 2

Sometimes 1

Not at all 0

A

I get a sort of frightened feeling like 'butterflies' in the stomach:

Not at all 0

Occasionally 1

Quite Often 2

Very Often 3

D

I have lost interest in my appearance:

Definitely 3

I don't take as much care as I should 2

I may not take quite as much care 1

I take just as much care as ever 0

A

I feel restless as I have to be on the move:

Very much indeed 3

Quite a lot 2

Not very much 1

Not at all 0

D

I look forward with enjoyment to things:

As much as I ever did 0

Rather less than I used to 1

Definitely less than I used to 2

Hardly at all 3

A

I get sudden feelings of panic:

Very often indeed 3

Quite often 2

Not very often 1

Not at all 0

D

I can enjoy a good book or radio or TV program:

Often 0

Sometimes 1

Not often 2

Very seldom 3

Appendix 6.4

383

EORTC QLQ-C30 (Version 3)

We are interested in some things about you and your health. Please answer all of the

questions yourself by circling the number that best applies to you. There are no "right"

or "wrong" answers. The information that you provide will remain strictly confidential.

Not

at all

A

Little

Quite

a bit

Very

much

1 Do you have any trouble doing strenuous

activities, like carrying a heavy shopping bag or

a suitcase?

1 2 3 4

2 Do you have any trouble taking a long walk? 1 2 3 4

3 Do you have any trouble taking a short walk

outside of the house?

1 2 3 4

4 Do you need to stay in bed or a chair during the

day?

1 2 3 4

5 Do you need help with eating, dressing,

washing yourself or using the toilet?

1 2 3 4


at all

A

Little

Quite

a bit

Very

much

6 Were you limited in doing either your work or

other daily activities?

1 2 3 4

7 Were you limited in pursuing your hobbies or

other leisure time activities?

1 2 3 4

8 Were you short of breath? 1 2 3 4

9 Have you had pain? 1 2 3 4

10 Did you need to rest? 1 2 3 4

11 Have you had trouble sleeping? 1 2 3 4

12 Have you felt weak? 1 2 3 4

13 Have you lacked appetite? 1 2 3 4

14 Have you felt nauseated? 1 2 3 4

15 Have you vomited? 1 2 3 4

Appendix 6.4

384


at all

A

Little

Quite

a bit

Very

much

16 Have you been constipated? 1 2 3 4

17 Have you had diarrhea? 1 2 3 4

18 Were you tired? 1 2 3 4

19 Did pain interfere with your daily activities? 1 2 3 4

20 Have you had difficulty in concentrating on

things, like reading a newspaper or watching

television?

1 2 3 4

21 Did you feel tense? 1 2 3 4

22 Did you worry? 1 2 3 4

23 Did you feel irritable? 1 2 3 4

24 Did you feel depressed? 1 2 3 4

25 Have you had difficulty remembering things? 1 2 3 4

26 Has your physical condition or medical

treatment interfered with your family life?

1 2 3 4


treatment interfered with your social activities?

1 2 3 4


treatment caused you financial difficulties?

1 2 3 4

For the following questions please circle the number between 1 and 7 that best

applies to you

29 How would you rate your overall health during the past week?

1 2 3 4 5 6 7

Very poor Excellent

30 How would you rate your overall quality of life during the past week?

1 2 3 4 5 6 7

Very poor Excellent

Appendix 6.4

385

EORTC QLQ-CR29


at all

A

Little

Quite

a bit

Very

much

31 Did you urinate frequently during the day? 1 2 3 4

32 Did you urinate frequently during the night? 1 2 3 4

33 Have you had any unintentional release

(leakage) of urine?

1 2 3 4

34 Did you have pain when you urinated? 1 2 3 4

35 Did you have abdominal pain? 1 2 3 4

36 Did you have pain in your buttock/anal/rectum? 1 2 3 4

37 Did you have a bloated feeling in your

abdomen?

1 2 3 4

38 Have you had blood in your stools? 1 2 3 4

39 Have you had mucus in your stools? 1 2 3 4

40 Did you have a dry mouth? 1 2 3 4

41 Have you lost hair as a result of your treatment? 1 2 3 4

42 Have you had problems with your sense of

taste?

1 2 3 4


at all

A

Little

Quite

a bit

Very

much

43 Were you worried about your health in the

future?

1 2 3 4

44 Have you worried about your weight?

1 2 3 4

45 Have you felt less physically attractive as a


1 2 3 4

46 Have you been feeling less feminine /

masculine as a result of your disease or

treatment?

1 2 3 4

47 Have you been dissatisfied with your body?

1 2 3 4

48 Do you have a stoma bag (colostomy /

ileostomy)? (please circle the correct answer)

yes no

Appendix 6.4

386


at all

A

Little

Quite

a bit

Very

much

Answer these questions ONLY IF YOU HAVE A STOMA BAG, if not please

continue below:


gas/flatulence from your stoma bag?

1 2 3 4

50 Have you had leakage of stools from your stoma

bag?

1 2 3 4

51 Have you had sore skin around your stoma?

1 2 3 4

52 Did frequent bag changes occur during the day?

1 2 3 4

53 Did frequent bag changes occur during the

night?

1 2 3 4

54 Did you feel embarrassed because of your

stoma?

1 2 3 4

55 Did you have problems caring for your stoma?

1 2 3 4



gas/flatulence from your back passage?

1 2 3 4

50 Have you had leakage of stools from your back

passage?

1 2 3 4

51 Have you had sore skin around your anal area?

1 2 3 4

52 Did frequent bowel movements occur during

the day?

1 2 3 4

53 Did frequent bowel movements occur during

the night?

1 2 3 4

54 Did you feel embarrassed because of your

bowel movement?

1 2 3 4

During the past 4 weeks: Not

at all

A

Little

Quite

a bit

Very

much

For men only:


57 Did you have difficulty getting or maintaining

an erection?

1 2 3 4

Appendix 6.4

387

For women only:


59 Did you have any pain or discomfort during

intercourse?

1 2 3 4

Appendix 6.4

388

SELF-EFFICACY SCALES

Self-efficacy is a measure of your personal belief, or confidence to succeed with your

goals to adopt and maintain a healthy lifestyle.

Please answer by circling the number that best applies to you.

1. The Nutrition Self-Efficacy Scale

“How certain are you that you could overcome the following barriers”

I can manage to stick to healthy foods, … Very

uncertain

Rather

uncertain

Rather

certain

Very

certain

1 …even if I need a long time to develop

the necessary routines.

1 2 3 4

2 …even if I have to try several times until

it works.

1 2 3 4

3 …even if I have to rethink my entire way

of nutrition.

1 2 3 4

4 …even if I do not receive a great deal of

support from others when making my

first attempts.

1 2 3 4

5 …even if I have to make a detailed plan. 1 2 3 4

2. The Physical Exercise Self-Efficacy Scale

“How certain are you that you could overcome the following barriers”

I can manage to carry out my exercise

intentions, …

Very

uncertain

Rather

uncertain

Rather

certain

Very

certain

1 …even when I have worries and

problems.

1 2 3 4

2 …even if I feel depressed. 1 2 3 4

3 …even when I feel tense. 1 2 3 4

4 …even when I am tired. 1 2 3 4

5 …even when I am busy. 1 2 3 4

Schwarzer, R. and B. Renner. Health-specific self-efficacy scales. 2005; Available from:

http://userpage.fu-berlin.de/health/healself.pdf.

Appendix 6.4

389

GLOBAL RATING OF CHANGE

Please circle the number/response that best applies to you, for each question.

1: “How does your fitness now, compare to your fitness at the start of the study?”

1 2 3 4 5 6 7

Much

better

Better A little

better

No change A little

worse

Worse Much

worse

2: “How do your pelvic floor symptoms / control now, compare to your pelvic floor

symptoms / control at the start of the study?”

1 2 3 4 5 6 7

Much

better

Better A little

better

No change A little

worse

Worse Much

worse

This is the end of the questionnaire booklet, thank you for very much for answering

these questions.

PLEASE BRING THIS QUESTIONNAIRE BOOKLET TO YOUR ASSESSMENT

APPOINTMENT.

Appendix 7.1

390


Appendix 7.1

391

Appendix 7.1

392

Appendix 7.1

393

Appendix 7.1

394

Appendix 7.2

395

Appendix 7.2 Data Collection Sheets (Study 5)


� Baseline (T1)

� Immediately post-Physiotherapy intervention (T2)

� Follow up at 6 months after baseline (T3)

DIGITAL ASSESSMENT

Latex allergy �1.Yes �2. No

Gel allergy �1.Yes �2. No

Verbal consent �1.Yes �2. No

1. OBSERVATION

a. Perianal condition 1. soiling �2. scarring �3.tags

�4.haemorrhoids

�5. prolapse 6. fissure � 7. excoriation 8.

other_____

b. Voluntary pelvic floor muscle contraction �1. Absent �2. Present

If absent, anorectal reflex 1. Absent �2. Present

If incorrect, correct after � 1st try � 2nd try � 3rd try

�still incorrect after 3 tries

2. DIGITAL PALPATION

Appropriate to perform digital palpation: �1.Yes � 2. No.

If No: �1. Recent anal surgery or trauma (< 6 weeks)

�2. Recent radiotherapy

�3. Acute pain related to active haemorrhoids/fissures etc

�4. Active inflammatory conditions

�5. Obvious bleeding

�6. Current infection

�7. other________________________________

a. IAS Resting Pressure �1. Increased �2. Normal �3. Reduced

b. Pain: �1.Yes �2. No

3. MUSCLE TESTING (3 x 3 sec reps, only 1 is MVC)

a. EAS

ICS Grade �1. Absent �2. Weak �3. Mod �4. Strong

b. Puborectalis

ICS Grade �1. Absent �2. Weak �3. Mod �4. Strong

c. Relaxation �1. Absent �2. Partial �3. Full

ANORECTAL AND PELVIC FLOOR MUSCLE TEST

Appendix 7.2

396

MANOMETRY

Appropriate to perform manometry: �1.Yes � 2. No.

If No: �1. current infection / pain

�2. swollen and painful haemorrhoid

�3. fissure

�4. excoriation / rash / erythema

�5. wound

�6. no voluntary squeeze observed

�7. other________________________________


1. a. 1 x 30 SEC MVC.

Resting pressure upon insertion (cm H2O)

Peak

Average

Gradient

Area under curve

b. Decision to discontinue due to poor technique

If yes, how many seconds:_______________

Reasons:

�1. Altered respiratory pattern

�2. Excessive use of external obliques

�3. Rectus abdominus activity

�4. Gluteal/adductor activity

�5. Other______________

TRANSPERINEAL ULTRASOUND


Variable

condition

Variable description Value

1. Rest a. distance levator hiatus (sagittal plane) A-P

direction (cm)

b. AR angle (degree)

c. distance AR angle to horizontal (cm)

2. Voluntary

contraction

1. 3 sec MVC

a. distance levator hiatus (sagittal plane) A-P

direction (cm)

b. AR angle (degree)

c. distance AR angle to horizontal (cm)

2. attempted 60 sec sustained contraction at

maximum: time to start of decay (from maximum

elevation) (seconds)

� If symptomatic, refer to the surgeon: date________________

Appendix 7.2

397

Bladder Diary (24 Hours)

Please complete this diary everyday for three days and post it back to us.

On the chart please record:

1. When you get out of bed in the morning, show this on the diary by writing ‘GOT

OUT OF BED’.

2. During the day please enter at the correct time the drinks you have during the day,

e.g. 8.00am – two cups of coffee (total 400 ml).

3. The time you pass your urine, e.g. 7.30am. Do this every time you pass urine

throughout the day and night.

4. Each time you pass urine, collect the urine in a measuring device and record the

amount (in unit) next to the time you passed the urine, eg.1.30pm/320cc.

5. Each time you pass your urine, please write down how urgent was the need to pass

urine:

‘O’ means it was not urgent. ‘+’ means I had to go within 10 minutes.

‘++’ means I had to stop what I was doing and go to the toilet.

6. If you leak urine, show this by writing a ‘W’ on the diary at the time you leaked.

7. If you leak, please add ‘P’ if you have to change a pad and ‘C’ if you have to

change your underclothes or even outer clothes. So if you leak and need to change

a pad, please write ‘WP’ at the time you leaked.

8. If you leak, please write in the column called ‘Comments’ whether you leaked a

small amount or a large amount and what you were doing when you leaked, e.g.

‘leaked small amount when I sneezed three times’.

9. Each time you change a pad or change clothes, please write in the ‘Comments’

column.

10. When you go to bed at the end of the day show it on the diary - write ‘Bed-time’.

Sample Time of day

Covers rising

time through to

bedtime, plus

during the night

Drinks

Types of

fluids (coffee,

tea, water,etc)

and how

much

Urine

Volume

Passed

Urgency Leakage

episodes

Circumstances/Comments

Morning

Got out of bed

7:15 am

- 200 o - -

11:30 am 10:00 am one

cup of coffee

400ml

275 ++ W Leaked small amount when

I sneezed three times. Wet

pants

Appendix 7.2

398

Time of day

Covers rising

time through to

bedtime, plus

during the night

Drinks

Types of

fluids (coffee,

tea, water,etc)

and how

much

Urine

Volume

Passed

Urgency Leakage

episodes


Morning

Got out of

bed…………..am

Breakfast ……...

am

Lunch ….….. pm

Afternoon

Evening

Dinner ……….

pm

Bed-time .……...

pm

During the night

Appendix 7.2

399

Time of day

Covers rising

time through to

bedtime, plus

during the night

Drinks

Types of

fluids (coffee,

tea, water,etc)

and how

much

Urine

Volume

Passed

Urgency Leakage

episodes


Morning

Got out of

bed…………..am

Breakfast ………

am

Lunch ….….. pm

Afternoon

Evening

Dinner ……….

Pm

Bed-time .………

pm

During the night

Appendix 7.2

400

Time of day

Covers rising

time through to

bedtime, plus

during the night

Drinks

Types of

fluids (coffee,

tea, water,etc)

and how

much

Urine

Volume

Passed

Urgency Leakage

episodes


Morning

Got out of

bed…………..am

Breakfast ……...

am

Lunch ….….. pm

Afternoon

Evening

Dinner ……….

pm

Bed-time .……...

pm

During the night

Appendix 7.2

401

BOWEL DIARY

Please fill out the chart below each day for seven days and post it back to us.

Sample: Date

& time

(dd/m

m/year

)

Urgency

(Yes/No)

If you

have to

rush to

toilet for

bowel

motion

Stool

Consistenc

y (see the

Bristol

Stool Form

Scale

attached)

Time

spent

at

toilet

Bowel

straini

ng

(Yes/

No)

Leakage/s

oiling or

bowel

accident

(Yes/No)

Use

of

pad

(Yes/

No)

Commen

t (e.g.

pain,

blood, or

certain

food

causing

bowel

problem)

Bowel

medicati

on

(medicati

on, fibre

suppleme

nts,

and/or

laxatives)

26/08/

2013

7.30am

Y Type 7 10

minute

s

N Y Y - -

30/08/

2013

8.00pm

N Type 2 20

minute

s

Y N N pain Coloxyl

with

Senna x 2

01/09/

2013

8.00pm

N Type 3 15

minute

s

N N N - -

Appendix 7.2

402

Reference: Heaton, K W & Lewis, S J 1997, 'Stool form scale as a useful guide to intestinal transit time'. Scandinavian Journal of

Gastroenterology, vol.32, no.9, pp.920 - 924. Retrieved on 2/3/2007.

Appendix 7.2

403

Date

& time

(dd/m

m/year

)

Urgency

(Yes/No)

If you

have to

rush to

toilet for

bowel

motion

Stool

Consistenc

y (see the

Bristol

Stool Form

Scale

attached)

Tim

e

spe

nt

at

toile

t

Bowel

straini

ng

(Yes/N

o)

Leakage/so

iling or

bowel

accident

(Yes/No)

Use of

pad

(Yes/N

o)

Comme

nt (e.g.

pain,

blood, or

certain

food

causing

bowel

problem)

Bowel

medicati

on

(medicati

on, fibre

suppleme

nts,

and/or

laxatives)

Appendix 8.1

404

Appendix 8.1 Systematic review article

Appendix 8.1

405

Appendix 8.1

406

Appendix 8.1

407

Appendix 8.1

408

Appendix 8.1

409

Appendix 8.1

410

Appendix 8.1

411

Appendix 8.1

412

Appendix 8.1

413

Appendix 8.2

414

Appendix 8.2 Example of search strategy

MEDLINE was searched using the Web of Knowledge interface on 10/03/2014 for

the period 1950 to March 2014

1. MeSH Heading:exp=(Rehabilitation) (141786)

2. MeSH Heading:exp=(Physical Therapy Modalities) (119321)

3. MeSH Heading=(Biofeedback Psychology) (6093)

4. Topic=(pelvic floor muscle training) (628)

5. Topic=(pelvic floor exercise) (1123)

6. Topic=(kegel) (122)

7. Topic=(biofeedback) (7821)

8. MeSH Heading:exp=(Defecation) (5501)

9. MeSH Heading:exp=(Fecal Incontinence) (7570)

10. Topic=(bowel function) (10987)

11. Topic=(gastrointestinal function) (21721)

12. Topic=(total mesorectal excision) (1477)

13. Topic=(sphincter-saving surgery) (516)

14. Topic=(anterior resection) (10805)

15. Topic=(Abdominoperineal resection) (2345)

16. MeSH Heading:exp=(Colectomy) (14382)

17. MeSH Heading:exp=(Colorectal Surgery) (1907)

18. Topic=(sphincter-preserving surgery) (465)

19. MeSH Heading:exp=(Colorectal Neoplasms) (141,110)

20. MeSH Heading:exp=(Rectal Neoplasms) (36,511)

21. MeSH Heading:exp=(Colonic Neoplasms) (65,271)

Appendix 8.2

415

22. 1 OR 2 OR 3 OR 4 OR 5 OR 6 OR 7 (235,136)

23. 8 OR 9 OR 10 OR 11 (41,226)

24. 12 OR 13 OR 14 OR 15 OR 16 OR 17 OR 18 (29,296)

25. 19 OR 20 OR 21 (141,110)

26. 22 AND 23 AND 24 AND 25 (35)

Refined by English (29)

Minerva Access is the Institutional Repository of The University of Melbourne

Author/s:Lin, Kuan-Yin

Title:Physical function in patients following surgery for colorectal cancer

Date:2016

Persistent Link:http://hdl.handle.net/11343/123734

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http://hdl.handle.net/11343/123734

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