i Swallowing Outcomes Following Primary Surgical Resection and Primary Free Flap Reconstruction for Oral and Oropharyngeal Squamous Cell Carcinomas: A Systematic Review of Quantitative Evidence Stephen Shih-Teng Kao Master of Clinical Science Joanna Briggs Institute Faculty of Health Sciences The University of Adelaide Australia October 2015
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i
Swallowing Outcomes Following Primary Surgical
Resection and Primary Free Flap Reconstruction
for Oral and Oropharyngeal Squamous Cell
Carcinomas: A Systematic Review of Quantitative
Evidence
Stephen Shih-Teng Kao
Master of Clinical Science
Joanna Briggs Institute
Faculty of Health Sciences
The University of Adelaide
Australia
October 2015
ii
Abstract
Background
Dysphagia is still a treatment related morbidity as organ preservation does not always
translate into function preservation despite advances in treatment modalities. The purpose of
this systematic review is to review the swallowing outcomes of patients with oral or
oropharyngeal squamous cell carcinoma following primary surgery with primary free flap
reconstruction with or without adjuvant therapy.
Objectives
The objective of this systematic review is to investigate swallowing outcomes following primary
surgical resection and free flap reconstruction for the treatment of patients with oral and
oropharyngeal squamous cell carcinoma. Dysphagia was evaluated with the use of objective
investigations (Videofluoroscopic swallowing studies, Fibreoptic endoscopic evaluations of
swallowing, Manometry, Gastrostomy dependency, Tracheostomy dependency) and
subjective questionnaires (MD Anderson Dysphagia Inventory, University of Washington
Quality of Life Questionnaire, Functional Oral Intake Score).
Inclusion criteria
This review considered studies which included patients with oral or oropharyngeal squamous
cell carcinoma treated with primary surgical resection and primary surgical reconstruction with
or without adjuvant therapy. Swallowing evaluation was conducted at six months or greater
after curative therapy. Objective outcome measures included gastrostomy dependency,
tracheostomy dependency, penetration-aspiration rates, oral and pharyngeal transit times or
pharyngeal pressure readings measured with either videofluoroscopic swallowing studies or
fibreoptic endoscopic evaluations of swallowing or manometry. Subjective outcomes were
measured with the MD Anderson Dysphagia inventory, University Washington Quality of Life
Questionnaire or Functional Oral Intake Scale.
Methods
A comprehensive search strategy was undertaken across MEDLINE, CINAHL, Embase, and
Scopus. Papers retrieved were assessed by two independent reviewers regarding study
design, study population, interventions, outcome measures, results and conclusions for each
article. Data extracted and analyzed for descriptive studies and findings presented in narrative
form.
iii
Results
15 studies were included in the systematic review, which consisted of eight cohort studies and
seven cases series. Postoperative radiotherapy was associated with worse swallowing
outcomes. Swallowing outcomes following the use of radial forearm free flap and anterolateral
thigh flap were inconclusive. Resections of the oropharynx demonstrated poorer swallowing
outcomes compared with oral cavity resections.
Conclusion
Radiotherapy has been demonstrated to be detrimental to swallowing function following
surgical resection and primary free flap reconstruction. Furthermore, swallowing function was
shown to improve with the use of free flap reconstruction compared with primary closure for
large tumor resections. From these results, a protocol for the identification of patients at low
or high risk of developing dysphagia has been proposed. There is, however, a lack of high
quality primary research regarding swallowing outcomes following primary surgery with
primary free flap reconstruction for oral and oropharyngeal squamous cell carcinoma.
iv
Acknowledgements
I would like to thank my supervisors, Dr Micah Peters and Dr Eng Ooi for their
guidance, feedback and support in completing the Thesis.
I would also like to acknowledge Maureen Bell, research librarian, for helping me
develop a comprehensive search strategy and Dr Sabapathy Krishnan my secondary
reviewer.
I would like to thank Doris, Huei-Jong and Wen-I for their unconditional love and
support. Furthermore, I would like to thank my four sisters (Jennifer, Alice, Rebecca
None of the studies included in this review evaluated swallowing outcomes utilizing
manometry or functional oral intake scale.
Surgery alone Vs. Surgery and Adjuvant Therapy
Shin was the only study to directly compare the MDADI scores of patients treated with surgery
alone against surgery with adjuvant therapy. They found postoperative RT to be associated
with poorer MDADI scores.9 They inferred tongue shrinkage following radiotherapy resulted in
decreased coordinated tongue movements, thus impairing swallowing efficiency. The studies
published by Winter and Li consisted of patients treated predominately with surgery and
adjuvant therapy.107, 108 Although there was no direct comparison regarding the effects of
postoperative RT, they both correlated postoperative RT with lower UW-QoL scores. Farace
was the only study to include patients treated with primary surgery alone, and found no
patients suffered from with aspiration at six months (Table 8).5 As they employed
nasoendoscopy for the measurement of OTT, results were not comparable to the other
included studies. Although the majority of included studies did not directly investigate the
effects of postoperative RT, poorer swallowing outcomes were inferred to be secondary to RT.
18, 102
34
Radial Forearm Free Flap Vs. Anterolateral Thig Flap
Radial forearm free flaps were utilized in 12 of the included studies.3-8, 18, 102, 106, 109 Chien found
improved muscular function with the thin pliable RFFF due to its smaller bulk compared with
the ALTF. However, overall they found no significant difference between the various flaps4
Five of the included studies solely utilized the RFFF and found its thin pliable attributes allow
it to integrate well with the oral cavity and oropharynx, thus leading to improved swallowing
outcomes. 3, 7, 8, 18, 106 Farace compared the RFFF and ALTF in the reconstruction of oral
defects and found no significant differences regarding functional outcomes.5 They suggested
the use of ALTF for intraoral reconstructions due to decreased donor site morbidity. Longo
also favored the ALTF due to lower donor site morbidity with reliable revascularization without
sacrificing the radial artery.17 They found the only drawback of the ALTF to be the large amount
of bulk potentially affecting movement of the neotongue, however, thinning was achievable
with careful dissection of the suprafascial plane.
Oral Cavity Vs. Oropharynx
Oropharyngeal resections lead to worse swallowing outcomes compared with oral cavity.
Resections of the soft palate in combination with the BOT had the most swallowing
complications including penetration and aspiration. 3 Resections of the soft palate, tongue
base, pharyngeal walls typically required reconstruction to decrease risk of strictures. 18
Tongue and FOM had poorer outcomes compared to buccal region. 108 Tracheostomy
dependency occurred in two patients in the included studies, of which both underwent
resections involving their oropharynx (Table 10).4, 18
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Chapter 4: Discussion
4.1. Overview of findings
Treatment modalities for oral and oropharyngeal squamous cell carcinomas have improved
oncological outcomes over recent years, with goals now aimed at improving functional
outcomes, such as swallowing. Numerous studies have investigated swallowing outcomes
following treatment of head and neck cancers. However, due to the complexity and multitude
of processes involved in deglutition, there is currently no standardized approach to the
assessment of swallowing. Postoperative deglutition function is a vital aspect in a patient's
quality of life, and thus a thorough and systematic approach must be applied in the evaluation
of these patients.
This systematic review sought to retrieve and synthesize the best available evidence on the
swallowing function of patients with oral or oropharyngeal squamous cell carcinoma treated
with primary surgery with primary free flap reconstruction with or without adjuvant therapy. A
total of eight cohort studies3-8, 17, 18 and seven case-series9, 102, 105-109 met the inclusion criteria
and methodological quality, were included in this review. There was a large variation in
methodological design and reporting of results in the included studies. Despite the lack of high
quality randomized data currently available, the included studies are a representative sample
of the current available literature. Large amounts of heterogeneity existed between these
published studies, thus causing difficulty in pooling of results for meta-analysis. The studies
included in this review evaluated patients with squamous cell carcinoma of varying sub-sites
of the oral cavity and oropharynx. The swallowing outcomes of varying sub-sites were typically
combined together due to the small population numbers available. This lead to decreased
validity in studies as differing sub-sites contributed to deglutition more than others. The
included studies also consisted of patients with varying stages of disease, ranging from T1 to
T4 and stage II to IV. This factor further added to the confounding biases commonly present
in surgical studies, as it is well established patients requiring larger resections will have poorer
swallowing outcomes.7, 111 In addition, differing surgical access techniques such as
mandibulotomies and peroral access have vastly different swallowing outcomes. Invasive
mandibulotomies involve disruption of the oral and pharyngeal anatomy and physiology,
typically leading to poorer outcomes. Lastly, preferences between surgeons and institutions
played a large role in functional outcomes. Therefore, findings in this study were presented in
narrative form due to the heterogeneity present in this review.
36
The included studies in this review have associated a dose-dependent relationship between
postoperative radiotherapy and worsening swallowing function. Shin was the only article to
specifically review this relationship, and found a significant decrease in MDADI score following
radiotherapy.9 Shin attributed this worsening swallowing function to excessive reconstructed
tissue shrinkage secondary to RT.9 Furthermore, two studies found no improvement in
swallowing function between six and twelve months following surgery and adjuvant RT.3, 7
Their findings were similar to the results from Pauloski, who also found minimal improvement
in swallowing function after RT.112 These findings suggest decreased healing ability in
combination with fibrosis, causing impaired swallowing function at six months following RT. In
addition, late complications of RT consisting of subcutaneous fibrosis, trismus and salivary
gland dysfunction all have a cumulative and detrimental impact on swallowing function.
Although this study did not focus specifically on these complications, the presence of these
effects is evidenced by prolonged gastrostomy dependency and increased transit times. The
findings from this review are further supported by other published reviews demonstrating
improved swallowing outcomes with surgery alone compared with surgery and adjuvant
CRT.46, 48 Moncrieff et al found evidence to support the use of primary surgery alone for the
treatment of T1 and T2 oropharyngeal SCC, thus avoiding the side effects of adjuvant RT.38
They recommended postoperative RT for local control of high-risk primaries or regional control
of bulky cervical metastases. Despite the great debate regarding optimal treatment of oral and
oropharyngeal SCC, the above findings demonstrate a potential for primary surgery-alone for
a select group of patients, thus sparing the effects of RT for these patients. Evidence from this
systematic review support the development of a protocol for the identification of patients at
high and low risk of developing post-treatment swallowing dysfunction. Furthermore, these
stratified patients should be monitored closely with a standardized swallowing protocol. This
proposed protocol will lead to improved understanding of dysphagia and better counseling for
patients preoperatively.
Currently published literature show promising results encouraging the use of swallowing
exercises to decrease the incidence of post-treatment dysphagia.113, 114 115-117 Scherpenhuizen
found statistically significant increased interincisal opening in patients who utilized jaw-
mobilizing device compared with no exercise.113 Furthermore, two randomized control trials
have found swallowing exercise programs associated with superior muscle maintenance and
functional swallowing ability.114, 115 MRI studies in the Carnaby-Mann study demonstrated
maintenance of muscle characteristics following swallowing exercises.115 They proposed the
“pharyngocise” protocol may be associated with decreased inflammatory changes following
treatment with CRT. Furthermore, Carroll and Kulbersh found pre-treatment swallowing
exercises to be correlated with improved swallowing function post-CRT.116, 117 These results
37
show promising results for the use of swallowing exercises pre- and during treatment for
patients undergoing CRT. These results, however, need to be validated with further research.
Microvascular free flap reconstructions have been employed in the reconstruction of surgical
defects as they allow for wider resection margins and are able to improve swallowing
outcomes by restoring tissue bulk.18, 118, 119 Hsiao found primary closure of the defect resulted
in a small mobile tongue which lacked volume and lead to ineffective deglutition.119 Flap
selection is dependent on the size and location of the defect, however, donor site morbidity
must be taken into account. Donor sites are associated with the potential of increased pain,
delayed wound healing and unsightly scars. All these factors need to be taken into account
prior to surgical resection and reconstruction. The majority of the cases included in this study
utilized RFFF, however, a small number of studies also employed the ALTF, RMF, VRAM and
LDF in their reconstructions. Farace and Longo suggested the use of the ALTF for
reconstruction, due to lower rates of donor site morbidity.5, 17 These findings are supported by
published literature favoring the use of ALTF due to its versatility, presence of abundant
perforating vessels and bulk for head and neck reconstructions.120 Systematic review
published by Lam, similarly found difficulty in concluding the ideal free flap for optimal
functional outcomes.74 Due to the heterogeneity involved in the studies, there is no clear
consensus on the efficacy of RFFF over ALTF for the reconstruction of oral or oropharyngeal
defects. Graft choice is largely dependent on the defect size as well as surgeon preference.
Compared with primary closure, microvascular reconstruction has been demonstrated to
improve deglutition.119 Hsiao was able to demonstrate the additional bulk was necessary to
close the dead space in the oral cavity, and allow for sufficient tongue to soft palate
contraction.109 Keiner recommended primary closure only for T1 tumors, as opposition of
adjacent mucosa in larger resections is not always possible.18 They also found scar tissue
formation, particularly in the oropharynx, lead to narrowing of the digestive tract. McConnel
found small resections of the oral or base of tongue demonstrated nil improvement in
swallowing efficiency between primary closure and flap repair.121 In larger resections, free
flaps have demonstrated versatility in being able to repair surgical defects without tethering
the tongue to surrounding structures.122, 123 Despite advances in microvascular reconstruction,
some studies demonstrated pharyngeal bolus transit time to be increased with no recovery to
preoperative function.3, 124 Lam found when tumor resection was limited to either oral tongue
or BOT, good functional outcome can be obtained through immediate free flap
reconstruction.74
38
Due to the complexity of swallowing and lack of standardization in its assessment, this
systematic review chose a combination of validated objective and subjective assessments to
evaluate swallowing function. Aspiration was noted to be a commonly utilized measure of
dysphagia among studies, with its detection via VFSS or nasoendoscopy. Penetration-
aspiration scale is a validated tool in quantifying the severity of penetration or aspiration, which
was only utilized in two studies.3, 7 The rate of aspiration was variable among studies, as
differing consistencies of food boluses were employed. The presence of aspiration is an
important factor to consider with regards to dysphagia, as it has the potential to lead to life-
threatening lower respiratory tract infections. The presence of persistent aspiration and
dysphagia results in the insertion of gastrostomy tubes and tracheostomies in some patients.
However, the presence of pneumonia was not utilized as an outcome of dysphagia as there
is great difficulty in ascertaining if the infection was secondary to aspiration or another cause.
Gastrostomy tubes were employed when there was a persistence of aspiration, severe
odynophagia, dysphagia or unable to maintain adequate nutrition. The included studies
showed a low rate of gastrostomy dependency, with removal typically prior to 12 months
following surgery. Other published systematic reviews similarly found variable rates of
gastrostomy dependency, ranging up to 75%.75 Haddock et al105 was the only study to
prophylactically insert gastrostomy tubes prior to treatment. Prophylactic gastrostomy tube
placement is practiced in some institutions with the goal of maintaining nutrition, avoiding
interruptions in treatment and improving tolerance and response to CRT.125-127 However,
studies have associated early gastrostomy tube insertion to be associated with long term
dysphagia and decreased quality of life, likely secondary to disuse muscle atrophy and
fibrosis.43, 128 Swallowing exercises have been employed in the treatment regime to reduce the
effects of CRT, with promising results. 114, 115 The presence of gastrostomy tubes as a marker
for dysphagia may be influenced by other factors, such as anxiety or lack of education involved
with the use of gastrostomy tubes.129 Therefore, it is important to utilize gastrostomy
dependency in conjunction with other assessment tools.
Tracheostomy dependency is not a commonly utilized measure of dysphagia in current
literature. It, however, plays a large role in swallowing function due to its potential to distort
pharyngeal anatomy and physiology when in situ. Tracheostomies are commonly conducted
in head and neck cancer cases involving large resections, as it allows for a definitive airway.
This was mentioned in six of the included studies.4, 6, 7, 17, 105, 106 Tracheostomy dependency
was low and occurred only in patients who underwent oropharyngeal resections, due to
recurrent aspiration or need for frequent pulmonary toileting. Thus tracheostomy dependency
is not only a marker for dysphagia, but is also a source of dysphagia. Despite the majority of
39
included studies in this systematic review performing mandibulotomies, the tracheostomy
dependency rates were similar to rates following transoral robotic surgery.48
Bolus transit time is an effective and versatile method of evaluating swallowing function. The
included studies measured a combination of oral, oropharyngeal and pharyngeal transit times.
Despite the lack of standardization in the measurement of bolus transit time, all studies based
their procedure on the study published by Lazarus and colleagues.130 The consistency used
varied between liquid and pudding in included studies, thus causing great difficulty in drawing
conclusions from the results. Due to its use in conjunction the VFSS, the movement of
anatomical structures can be assessed during the same procedure. However, due to the vastly
differing measures of movement in pharyngeal structures available, this was not used in the
review.
Manometry is a gold standard for the assessment of esophageal motility disorders, however,
is technically demanding and requires experienced and specialized staff. Manometry is
typically used in the investigation of dysphagia, however, is only performed when diagnosis
has not been achieved with other forms of investigations. The complexity of this procedure
causes difficulty in access to this form of investigation, thus it is the likely reason none of the
included studies utilized manometry as an evaluation method of swallowing function.
However, studies have demonstrated the important role of impedance manometry as an
alternative non-radiological method in the assessment of oropharyngeal swallowing
disorders.131
Subjective questionnaires are integral to the evaluation of dysphagia in patients following
cancer therapy. It provides clinicians with important information regarding the patient's
perception of their physical and emotional state. Therefore, it is extremely important to
combine both objective and subjective methods for a more holistic management regime. The
MD Anderson Dysphagia Inventory (MDADI) and University Washington Quality of Life
Questionnaire (UW-QoL) have both been validated for use in head and neck cancer patients.
The included studies that utilized subjective questionnaires showed similar scores among the
patients treated. Interestingly, Kendall and colleagues demonstrated a lack of correlation in
quality of life and physiological functioning.132 It is important to consider the questionnaires
measure the patient's emotional response to their disease and different aspects of their life.
This association between objective and subjective evaluations require further research.
Swallowing evaluation is an integral component in the management of patients following
treatment of head and neck malignancy. Due to the complexity of dysphagia, there is not a
40
standardized protocol for post-treatment swallowing evaluation. A wide range of assessment
tools is currently available to clinicians, ranging from subjective questionnaires to bedside
nasoendoscopy to videofluoroscopy in the radiology suites. Despite these advances in
assessments available, there is a lack of published literature investigating swallowing in a
standardized manner. There is a need for a well-designed prospective longitudinal cohort
study to assist furthering our knowledge on post-treatment swallowing outcomes. VFSS and
FEES should be utilized routinely in the evaluation of dysphagia, as they are able to provide
large amounts of information regarding deglutition. Detection of aspiration is paramount in
decreasing rates of aspiration pneumonia, thus improving quality of life. Ideally, the evaluation
of aspiration with the use of the validated penetration-aspiration scale allows quantitative
grading. Due to the late toxicities following the CRT, more studies are required to evaluate
long term swallowing outcomes greater than one to two years. Studies should aim to include
both objective investigations with subjective questionnaires for a more holistic approach. A
standardized protocol for the measurement of transit time and movement of pharyngeal
structures should be developed and validated, thus allowing for in-depth investigation of
changes following treatment with CRT.
4.2. Limitations to the study
The search strategy for this systematic review was limited to studies published in English.
Therefore, studies published in languages other than English may have added to the findings
in this review. Furthermore, there was a lack of high quality studies due to the nature of the
topic. Improvements in methodology and reporting of data is required for future studies.
Primary studies should include clearly documented inclusion and exclusion criteria with
surgical resection and reconstruction techniques clearly described. Patients with malignancies
of similar stage should be grouped together. Additionally, results from swallowing evaluations
should be clearly documented.
4.3. Implications for practice
This review included studies of varying methodological quality by the critical appraisal process.
Due to the nature of this topic, high quality evidence is currently limited. Interpretation of the
findings provide credible evidence useful in clinical practice with the potential to produce useful
strategies in identifying patients at high risk of developing dysphagia post-treatment, and in
turn have appropriate swallowing evaluations and follow up. A number of recommendations
for practice have been developed based upon the results of this review which have been
graded using the JBI approach. Grades of Recommendation are used to assist healthcare
professionals when implementing evidence into practice.
41
The JBI Levels of Evidence and Grades of Recommendations is based on the JBI "FAME
Model" of feasibility, appropriateness, meaningfulness and effectiveness.133 Grade A
recommendations are considered "strong" recommendations, whereas, Grade B
recommendations, are considered "weak" recommendations for a health management
strategy. Due to the quality of included studies and current available literature, the
recommendations from this review are Grade B.
Based upon the findings from this systematic review, it can be recommended that patients
receiving treatment for their oral and oropharyngeal squamous cell carcinoma are identified
early by using a validated screening protocol that stratifies patients into low and high risk of
developing post-treatment dysphagia. A draft protocol for dysphagia risk stratification for the
assessment of patients diagnosed with oral and oropharyngeal squamous cell carcinomas
was developed (Appendix VII). Such a protocol will also be able to be used to facilitate
counselling for patients with regard to their likelihood of experiencing post-treatment
dysphagia. The proposed protocol contains the following recommendations for practice:
Low risk patients with early stage malignancy (T1 and T2) with no evidence of regional or
distant metastases, may benefit with less dysphagia from surgery-alone without
radiotherapy to the primary tumor. (Grade B)
Larger resections involving combinations of the BOT, oral tongue and soft palate with the
addition of RT following resection would be deemed higher risk to be associated with long-
term dysphagia. (Grade B)
Preoperatively, all patients require evaluation with FEES and subjective questionnaires.
(Grade B)
Postoperatively, patients should be closely monitored with quality of life questionnaires
and routine FEES to evaluate for aspiration, with use the aspiration-penetration scale.
(grade B)
Patients deemed higher risk will require closer monitoring with the use of VFSS pre- and
postoperatively. (Grade B)
4.4. Implications for research
There was a lack of high level evidence in the area of swallowing outcomes following primary
surgery and primary free flap reconstruction. Due to ethical concerns, no high quality
randomized control trials have been published. The only available literature on this topic are
cohort and case-series studies. These studies require clearly defined inclusion and exclusion
criteria with detailed descriptions of surgical techniques and adjuvant therapies involved.
42
Furthermore, different stages and sub-sites of cancer must ideally be stratified separately to
decrease confounding factors. All these elements must be addressed to produce a high quality
study. A standardized protocol of swallowing function is required, consisting of both objective
and subjective assessments. Subjective assessments such as the MDADI and UW-QoL are
both validated questionnaires that should be routinely utilized. These subjective findings
should be utilized with findings from objective investigations for a holistic approach. The
reporting of these outcomes must be standardized and detailed for it to be used in a meta-
analysis. The use of the dysphagia risk stratification protocol is recommended to be used in
clinical practice. Patients stratified into the low and high risk groups should be followed
prospectively, monitored with both objective and subjective swallowing evaluations. The long
term outcomes of these patients should be documented clearly, and will assist in validating
the effectiveness of this protocol. A prospective multi-centered approach would be a preferred
method of performing a high quality study.
4.5. Conclusion
Swallowing function is a fundamental component in the management of patients following
treatment of head and neck malignancy. Due to the intricacy of swallowing, there is yet to be
a standardized protocol for post-treatment dysphagia evaluation. A vast array of objective and
subjective assessment tools are currently available, however, there is still a lack of published
literature investigating swallowing in a standardized manner.
This systematic review has retrieved and collated the best available evidence in the literature
on swallowing outcomes following primary surgical resection with primary free flap
reconstruction. Results have found that postoperative radiotherapy has been demonstrated to
adversely affect swallowing outcomes. Furthermore, there is currently no consensus regarding
swallowing outcomes between the use of radial forearm free flaps and anterolateral thigh flaps,
both appear to be efficacious. Lastly, primary free flap reconstruction has been demonstrated
to have improved swallowing outcomes compared with primary closure.
There is a need for a well-designed prospective longitudinal cohort study to assist furthering
our knowledge on post-treatment swallowing outcomes. Furthermore, long term studies are
required to review late toxicities following CRT. Studies should aim to combine both objective
investigations with subjective questionnaires for a more holistic approach. A standardized
protocol for identifying low and high risk patients with corresponding swallowing evaluations
has been proposed.
43
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50
Appendix I: Search Strategy
The following PubMed logic grid was adapted and utilized for all included databases searched,
with search limits consisting of only English and Human studies.
Oral or Oropharyngeal SCC Dysphagia Primary Free Flap Reconstruction
oropharyngeal neoplasms[mh] OR
deglutition
disorders[mh:noexp] OR surgical flaps[mh] OR
oropharyngeal neoplasm*[tw] OR
deglutition disorder*[tw]
OR free tissue flaps[mh] OR
oropharyngeal squamous cell
carcinoma*[tw] OR dysphagi*[tw] OR surgical flap*[tw] OR
oropharyngeal SCC[tw] OR swallow*[tw] OR tissue flap*[tw] OR
oropharyngeal cancer*[tw] OR deglutition[tw] free flap*[tw] OR
oropharyngeal carcinoma[tw] OR tissue graft*[tw] OR
oropharyngeal tumo*[tw] OR microvascular reconstruction*[tw] OR
oropharynx cancer*[tw] OR microsurgical free flap[tw] OR
oropharynx neoplasm*[tw] OR recontruct*[tw]
oropharynx carcinoma*[tw] OR
oropharynx tumo*[tw] OR
oropharynx squamous cell
carcinoma*[tw] OR
oropharynx SCC[tw] OR
mouth neoplasms[mh] OR
mouth neoplasm*[tw] OR
mouth cancer*[tw] OR
mouth carcinoma*[tw] OR
mouth tumo*[tw] OR
mouth SCC[tw] OR
mouth squamous cell carcinoma*[tw]
OR
oral neoplasm*[tw] OR
oral cancer*[tw] OR
oral carcinoma*[tw] OR
oral tumo*[tw] OR
51
oral SCC[tw] OR
oral squamous cell carcinoma*[tw] OR
oral cavity neoplasm*[tw] OR
oral cavity cancer*[tw] OR
oral cavity carcinoma*[tw] OR
oral cavity tumo*[tw] OR
oral cavity SCC[tw] OR
oral cavity squamous cell
carcinoma*[tw] OR
intraoral neoplasm*[tw] OR
intraoral cancer*[tw] OR
intraoral carcinoma*[tw] OR
intraoral tumo*[tw] OR
intraoral SCC[tw] OR
intraoral squamous cell carcinoma*[tw]
Pubmed searched 26/03/2015 => 241
- Search limits: English, Humans
(((oropharyngeal neoplasms[mh] OR oropharyngeal neoplasm*[tw] OR oropharyngeal
squamous cell carcinoma*[tw] OR oropharyngeal SCC[tw] OR oropharyngeal cancer*[tw] OR
oropharyngeal carcinoma[tw] OR oropharyngeal tumo*[tw] OR oropharynx cancer*[tw] OR
oropharynx neoplasm*[tw] OR oropharynx carcinoma*[tw] OR oropharynx tumo*[tw] OR
oropharynx squamous cell carcinoma*[tw] OR oropharynx SCC[tw] OR mouth neoplasms[mh]
OR mouth neoplasm*[tw] OR mouth cancer*[tw] OR mouth carcinoma*[tw] OR mouth
tumo*[tw] OR mouth SCC[tw] OR mouth squamous cell carcinoma*[tw] OR oral neoplasm*[tw]
OR oral cancer*[tw] OR oral carcinoma*[tw] OR oral tumo*[tw] OR oral SCC[tw] OR oral
squamous cell carcinoma*[tw] OR oral cavity neoplasm*[tw] OR oral cavity cancer*[tw] OR
oral cavity carcinoma*[tw] OR oral cavity tumo*[tw] OR oral cavity SCC[tw] OR oral cavity
squamous cell carcinoma*[tw] OR intraoral neoplasm*[tw] OR intraoral cancer*[tw] OR
intraoral carcinoma*[tw] OR intraoral tumo*[tw] OR intraoral SCC[tw] OR intraoral squamous
cell carcinoma*[tw])) AND (deglutition disorders[mh:noexp] OR deglutition disorder*[tw] OR
dysphagi*[tw] OR swallow*[tw] OR deglutition[tw])) AND (surgical flaps[mh] OR free tissue
flaps[mh] OR surgical flap*[tw] OR tissue flap*[tw] OR free flap*[tw] OR tissue graft*[tw] OR
microvascular reconstruction*[tw] OR microsurgical free flap[tw] OR recontruct*[tw])
52
Embase searched 26/03/2015 => 120
- Search limits: English, Humans
(oropharynx tumor'/syn OR 'oropharynx tumor'/exp OR 'oropharynx cancer':ab,ti OR
'oropharynx cancers':ab,ti OR 'oropharynx carcinoma':ab,ti OR 'oropharynx
carcinomas':ab,ti OR 'oropharynx neoplasm':ab,ti OR 'oropharynx neoplasms':ab,ti OR
'oropharynx tumor':ab,ti OR 'oropharynx tumors':ab,ti OR 'oropharynx tumour':ab,ti OR
'oropharynx tumours':ab,ti OR 'oropharynx squamous cell carcinoma':ab,ti OR
'oropharynx squamous cell carcinomas':ab,ti OR 'oropharynx scc':ab,ti OR
'oropharyngeal cancer':ab,ti OR 'oropharyngeal cancers':ab,ti OR 'oropharyngeal
carcinoma':ab,ti OR 'oropharyngeal carcinomas':ab,ti OR 'oropharyngeal
neoplasm':ab,ti OR 'oropharyngeal neoplasms':ab,ti OR 'oropharyngeal tumor':ab,ti OR
'oropharyngeal tumors':ab,ti OR 'oropharyngeal tumour':ab,ti OR 'oropharyngeal
tumours':ab,ti OR 'oropharyngeal squamous cell carcinoma':ab,ti OR 'oropharyngeal
squamous cell carcinomas':ab,ti OR 'oropharyngeal scc':ab,ti OR 'mouth tumor'/syn OR
'mouth tumor'/exp OR 'mouth tumour':ab,ti OR 'mouth tumours':ab,ti OR 'mouth
tumor':ab,ti OR 'mouth tumors':ab,ti OR 'mouth neoplasm':ab,ti OR 'mouth
neoplasms':ab,ti OR 'mouth cancer':ab,ti OR 'mouth cancers':ab,ti OR 'mouth
carcinoma':ab,ti OR 'mouth carcinomas':ab,ti OR 'mouth scc':ab,ti OR 'mouth squamous
cell carcinoma':ab,ti OR 'mouth squamous cell carcinomas':ab,ti OR 'oral tumour':ab,ti
OR 'oral tumours':ab,ti OR 'oral tumor':ab,ti OR 'oral tumors':ab,ti OR 'oral
neoplasm':ab,ti OR 'oral neoplasms':ab,ti OR 'oral cancer':ab,ti OR 'oral cancers':ab,ti OR
'oral carcinoma':ab,ti OR 'oral carcinomas':ab,ti OR 'oral scc':ab,ti OR 'oral squamous
cell carcinoma':ab,ti OR 'oral squamous cell carcinomas':ab,ti OR 'oral cavity
tumour':ab,ti OR 'oral cavity tumours':ab,ti OR 'oral cavity tumor':ab,ti OR 'oral cavity
tumors':ab,ti OR 'oral cavity neoplasm':ab,ti OR 'oral cavity neoplasms':ab,ti OR 'oral
cavity cancer':ab,ti OR 'oral cavity cancers':ab,ti OR 'oral cavity carcinoma':ab,ti OR 'oral
cavity carcinomas':ab,ti OR 'oral cavity scc':ab,ti OR 'oral cavity squamous cell
carcinoma':ab,ti OR 'oral cavity squamous cell carcinomas':ab,ti OR 'intraoral
tumour':ab,ti OR 'intraoral tumours':ab,ti OR 'intraoral tumor':ab,ti OR 'intraoral
tumors':ab,ti OR 'intraoral neoplasm':ab,ti OR 'intraoral neoplasms':ab,ti OR 'intraoral
cancer':ab,ti OR 'intraoral cancers':ab,ti OR 'intraoral carcinoma':ab,ti OR 'intraoral
carcinomas':ab,ti OR 'intraoral scc':ab,ti OR 'intraoral squamous cell carcinoma':ab,ti OR
'intraoral squamous cell carcinomas':ab,ti) AND (dysphagi*:de,ab,ti OR 'deglutition
disorder':ab,ti OR 'deglutition disorders':ab,ti OR swallow*:ab,ti OR deglutition:ab,ti) AND
('free tissue graft':de,ab,ti OR 'free tissue graft'/syn OR 'surgical flap':ab,ti OR 'surgical
flaps':ab,ti OR 'free flap':ab,ti OR 'free flaps':ab,ti OR 'tissue graft':ab,ti OR 'tissue
grafts':ab,ti OR 'tissue flap':ab,ti OR 'tissue flaps':ab,ti OR 'microvascular
53
reconstruction':ab,ti OR 'microsurgical free flap':ab,ti OR 'microsurgical free flaps':ab,ti
OR recontruct:de,ab,ti)
CINAHL Searched 26/03/2015 =>12
- Search limits: English, Humans
(MH pharyngeal squamous cell carcinoma* OR AB oropharyngeal squamous cell carcinoma*
OR TI oropharyngeal neoplasm* OR AB oropharyngeal neoplasm* OR TI oropharyngeal
cancer* OR AB oropharyngeal cancer* OR TI oropharyngeal carcinoma* OR AB
oropharyngeal carcinoma* OR TI oropharyngeal tumo* OR AB oropharyngeal tumo* OR TI
oropharynx SCC OR AB oropharynx SCC OR TI oropharynx squamous cell carcinoma* OR
AB oropharynx squamous cell carcinoma* OR TI oropharynx neoplasm* OR AB oropharynx
neoplasm* OR TI oropharynx cancer* OR AB oropharynx cancer* OR TI oropharynx
carcinoma* OR AB oropharynx carcinoma* OR TI oropharynx tumo* OR AB oropharynx tumo*
MH mouth neoplasms OR TI mouth neoplas* OR AB mouth neoplas* OR TI mouth cancer*
OR AB mouth cancer* OR TI mouth carcinoma* OR AB mouth carcinoma* OR TI mouth tumo*
OR AB mouth tumo* OR TI mouth SCC OR AB mouth SCC OR TI mouth squamous cell
carcinoma* OR AB mouth squamous cell carcinoma* OR TI oral neoplas* OR AB oral neoplas*
OR TI oral cancer* OR AB oral cancer* OR TI oral carcinoma* OR AB oral carcinoma* OR TI
oral tumo* OR AB oral tumo* OR TI oral SCC OR AB oral SCC OR TI oral squamous cell
carcinoma* OR AB oral squamous cell carcinoma* OR TI oral cavity neoplas* OR AB oral
cavity neoplas* OR TI oral cavity cancer* OR AB oral cavity cancer* OR TI oral cavity
carcinoma* OR AB oral cavity carcinoma* OR TI oral cavity tumo* OR AB oral cavity tumo*
OR TI oral cavity SCC OR AB oral cavity SCC OR TI oral cavity squamous cell carcinoma*
OR AB oral cavity squamous cell carcinoma* OR TI intraoral neoplas* OR AB intraoral
neoplas* OR TI intraoral cancer* OR AB intraoral cancer* OR TI intraoral carcinoma* OR AB
intraoral carcinoma* OR TI intraoral tumo* OR AB intraoral tumo* OR TI intraoral SCC OR AB
intraoral SCC OR TI intraoral squamous cell carcinoma* OR AB intraoral squamous cell
carcinoma* ) AND ( MH deglutition disorder OR TI deglutition disorder* OR AB deglutition
disorder* OR TI swallow* OR AB swallow* OR TI deglutition OR AB deglutition OR TI
dysphagi* OR AB dysphagi* ) AND ( MH surgical flaps OR TI sugical flap* OR AB surgical
flap* OR TI free tissue flap* OR AB free tissue flap* OR TI tissue flap* OR AB tissue flap* OR
TI free flap* OR AB free flap* OR TI tissue graft* OR AB tissue graft* OR TI microvascular
reconstruction* OR AB microvascular reconstruction* OR TI microsurgical free flap* OR
microsurgical free flap* OR TI recontruct* OR AB recontruct* )
54
Appendix II: Critical Appraisal Instruments
55
56
57
Appendix III: Data Extraction Instruments
58
Appendix IV: Authors Contacted
Archontaki M, Athanasiou A, Stavrianos SD, Korkolis DP, Faratzis G, Papadopoulou F, et al. Functional results
of speech and swallowing after oral microvascular free flap reconstruction. Eur Arch Otorhinolaryngol.
2010;267(11):1771-7.
Barata LF, De Carvalho GB, Carrara-De Angelis E, De Faria JCM, Kowalski LP. Swallowing, speech and quality
of life in patients undergoing resection of soft palate. Eur Arch Otorhinolaryngol. 2013;270(1):305-12.
Brown JS, Rogers SN, Lowe D. A comparison of tongue and soft palate squamous cell carcinoma treated by
primary surgery in terms of survival and quality of life outcomes. Int J Oral Maxillofac Surg. 2006;35(3):208-14.
Brown L, Rieger JM, Harris J, Seikaly H. A longitudinal study of functional outcomes after surgical resection and
microvascular reconstruction for oral cancer: tongue mobility and swallowing function. Journal of Oral &
Maxillofacial Surgery (02782391). 2010;68(11):2690-700.
Gabr EM, Kobayashi MR, Salibian AH, Armstrong WB, Sundine M, Calvert JW, et al. Oromandibular
reconstruction with vascularized free flaps: A review of 50 cases. Microsurgery. 2004;24(5):374-7.
Gabr EM, Kobayashi MR, Salibian AH, Armstrong WB, Sundine M, Calvert JW, et al. Role of ulnar forearm free
flap in oromandibular reconstruction. Microsurgery. 2004;24(4):285-8.
Kalavrezos N, Cotrufo S, Govender R, Rogers P, Pirgousis P, Balasundram S, et al. Factors affecting swallow
outcome following treatment for advanced oral and oropharyngeal malignancies. Head Neck. 2014;36(1):47-54.
Li W, Li R, Safdar J, Huang S, Xu Z, Tan X, et al. Modified visor approach applied to total or subtotal
glossectomy and reconstruction: avoidance of lip splitting and mandibulotomy and cutting off mental nerve.
Tumour Biol. 2014;35(8):7847-52.
Lv M, Shen Y, Li J, Zhang C, Zhu H, Sun J. Immediate reconstruction of soft palate defects after ablative surgery
and evaluation of postoperative function: an analysis of 45 consecutive patients. J Oral Maxillofac Surg.
2014;72(7):1397-406.
Markkanen-Leppanen M, Isotalo E, Makitie AA, Rorarius E, Asko-Seljavaara S, Pessi T, et al. Swallowing after
free-flap reconstruction in patients with oral and pharyngeal cancer. Oral Oncol. 2006;42(5):501-9.
Navach V, Zurlo V, Calabrese L, Massaro MA, Bruschini R, Giugliano G, et al. Total glossectomy with
preservation of the larynx: oncological and functional results. Br J Oral Maxillofac Surg. 2013;51(3):217-23.
Pierre CS, Dassonville O, Chamorey E, Poissonnet G, Riss JC, Ettaiche M, et al. Long-term functional outcomes
and quality of life after oncologic surgery and microvascular reconstruction in patients with oral or oropharyngeal
cancer. ActaOtolaryngol. 2014;134(10):1086-93.
Vega C, Leon X, Cervelli D, Pons G, Lopez S, Fernandez M, et al. Total or subtotal glossectomy with
microsurgical reconstruction: functional and oncological results. Microsurgery. 2011;31(7):517-23.
Villaret AB, Cappiello J, Piazza C, Pedruzzi B, Nicolai P. Quality of life in patients treated for cancer of the oral
cavity requiring reconstruction: a prospective study. ActaOtorhinolaryngol Ital. 2008;28(3):120-5.
Zafereo ME, Weber RS, Lewin JS, Roberts DB, Hanasono MM. Complications and functional outcomes following
complex oropharyngeal reconstruction. Head Neck. 2010;32(8):1003-11.
Zuydam AC, Lowe D, Brown JS, Vaughan ED, Rogers SN. Predictors of speech and swallowing function
following primary surgery for oral and oropharyngeal cancer. ClinOtolaryngol. 2005;30(5):428-37.
59
Appendix V: Included Studies
Author Method Population Site Stage Type of Resection Flap Outcome
Measures
Time of
Assessment
(Months)
Adjuvant
Therapy
Borggreven3 Prospective
Cohort 54
Oral tongue,
FOM, BOT,
Tonsil, Soft
palate
II, III,
IV
Paramedian mandibular
swing for access
Composite resection with
microvascular soft tissue
transfer
RFFF
Oral and
pharyngeal
transit time
Aspiration (PAS)
6, 12 RT
Chien4 Prospective
Cohort 29
Oral tongue,
BOT T3, T4
Partial or total glossectomy
via mandibulotomy
RFFF
ALTF
Tracheostomy
Dependency
G-tube
Dependency
Aspiration
12 CRT
Farace5 Prospective
Cohort 20 Oral cavity T2, T3
Intraoral soft tissue ablation:
Hemiglossectomy, anterior
pavement ablation
RFFF
ALTF Aspiration 6 Unclear
Haddock105 Retrospective
Case-series 8 Oral tongue III, IV Subtotal or total glossectomy VRAM
Tracheostomy
Dependency
G-tube
Dependency
Aspiration
12 RT
Hartl102 Prospective
Case-series 5
Oral tongue,
BOT IV Subtotal or total glossectomy
RFFF
LDF
RMF
Aspiration 18-83 RT
Hsiao109 Prospective
Case-series 4 Oral tongue T2, T3
Hemiglossectomy +
Mandibulotomy RFFF Oral transit time 6 CRT
60
Keiner18 Prospective
Cohort 150
Oral cavity,
Oropharynx
T2, T3,
T4
Tumor resection through
transoral or lateral
pharyngotomy approach
RFFF
Tracheostomy
Dependency
Aspiration
8-15 RT
Li108 Retrospective
Case-series 51
Oral tongue,
FOM, Gum,
Buccal mucosa
T1, T2,
T3, T4 Unclear ALTF UW-QoL 12-84 CRT
Longo17 Prospective
Cohort 13 Oral tongue T3, T4
Anterior total mobile tongue
resection, subtotal tongue
resection
ALTF
Oral transit time
Tracheostomy
dependency
18 RT
Moerman106 Prospective
Case-series 4
Tonsil, Soft
palate, Lateral
pharyngeal wall
T2, T3 WLE of lateral pharyngeal
wall, RMT, Soft palate RFFF
Tracheostomy
Dependency 8-21 RT
O'Connell6 Prospective
Cohort 20
BOT, Lateral
pharyngeal
wall, Soft palate
III, IV
Lip-splitting incision and
presymphyseal
mandibulotomy
RFFF
Tracheostomy
Dependency
G-tube
dependency
Aspiration (PAS)
12 CRT
Rieger7 Prospective
Cohort 32
BOT, Lateral
pharyngeal
wall, Soft palate
T1, T2,
T3, T4
Lip-splitting incision and
presymphyseal
mandibulotomy
RFFF
Tracheostomy
Dependency
G-tube
dependency
Aspiration (PAS)
Oral and
pharyngeal
transit time
Preoperatively,
1, 6 , 12 CRT
Seikaly8 Prospective
Cohort 18
BOT, Lateral
pharyngeal
wall, Soft palate
III, IV
Oropharynx resection, lip split
incision and parasymphyseal
mandibulotomy
RFFF
G-tube
dependency
Aspiration
1, 6, 9, 12 RT
61
Shin9 Retrospective
Case-series 31 Oral tongue T1, T2
Partial glossectomy
performed through peroral
approach, pull through or
paramedian mandibulotomy
RFFF MDADI 21-91 RT
Winter107 Prospective
Case-series 6 BOT III, IV
Resection of tongue base
with mandibulotomy, per oral
resection or lingual release
RFFF,
RMF UW-QOL 9-56 RT
BOT: Base of tongue; FOM: Floor of mouth; RMT: Retromolar trigone; WLE: Wide local excision; RFFF: Radial forearm free flap; ALFT: Anterolateral thigh