UROLOGIC LAPAROENDOSCOPIC SINGLE-SITE SURGERY (LESS)- MULTIINSTITUTIONAL ANALYSIS OF RISK FACTORS FO

The Journal of Urology

UROLOGIC LAPAROENDOSCOPIC SINGLE-SITE SURGERY (LESS): MULTI-INSTITUTIONAL ANALYSIS OF RISK FACTORS FOR CONVERSIONS AND

POSTOPERATIVE COMPLICATIONS--Manuscript Draft--

Manuscript Number: JU-11-1768R1

Full Title: UROLOGIC LAPAROENDOSCOPIC SINGLE-SITE SURGERY (LESS): MULTI-INSTITUTIONAL ANALYSIS OF RISK FACTORS FOR CONVERSIONS ANDPOSTOPERATIVE COMPLICATIONS

Article Type: Adult Urology Article

Keywords: Conversions, Complications, Laparoendoscopic single-site surgery, Multi-institutional,Single port laparoscopy, LESS, scarless surgery, urology

Corresponding Author: Riccardo Autorino, MD, PhD, FEBUSecond University of NaplesNaples, NA ITALY

Corresponding Author SecondaryInformation:

Corresponding Author's Institution: Second University of Naples

Corresponding Author's SecondaryInstitution:

First Author: Riccardo Autorino, MD, PhD, FEBU

First Author Secondary Information:

All Authors: Riccardo Autorino, MD, PhD, FEBU

All Authors Secondary Information:

Manuscript Region of Origin: USA

Abstract: Purpose. To analyze the incidence of and the risk factors for complications andconversions in a large contemporary series of patients undergoing urologic LESS.Methods. Study cohort consisted of consecutive patients treated with LESS betweenAugust 2007 and December 2010 at 20 institutions. Logistic regression model wasused for the following analyses: risk of conversion; risk of postoperative complicationsof any grade and of high grade only.Results. One thousand one hundred and sixty three cases were included in theanalysis. Intraoperative complications occurred in 3.3% of cases. The overallconversion rate was 19.6% with 14.6%, 4% and 1.1% converted to "reduced port"laparoscopy, conventional laparoscopy/robotic and open surgery, respectively. Onmultivariable analysis, the factors resulting to be significantly associated with risk ofconversion were oncologic surgical indication (p=0.02), pelvic surgery (p<0.001),robotic approach (p<0.001), high difficulty score (p=0.004), extended OR time(p=0.03), and the occurrence of an intraoperative complication (p=0.001). A total of 120postoperative complications occurred in 109 patients (9.4%) with major ones in just2.4% of the entire cohort. Reconstructive procedure (p=0.03), high difficulty score(p=0.002) and extended OR time (p=0.02) were identified as predictors of high gradecomplications.Conclusions. Urologic LESS can be performed with low complication rates, resemblingthose observed in laparoscopic series. The conversion rates suggest that earlyadopters of the technique have adhered to the principles of careful patient selectionand safety. Besides facilitating future comparisons across institutions, this analysis canbe useful in counseling patients regarding the current risks of urologic LESS.

Suggested Reviewers:

Opposed Reviewers:

Response to Reviewers: Reviewer #1:

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• Abstract: Only the first sentence is supported by the data presented. The ideabrought out in the second sentence should be further developed in the discussion sothat the novice to LESS would clearly know what types of patients give the highestchance of success.We tried to further stress this in the discussion (page 12): “…this analysis is likely toprovide some guidance to the urologist novice to LESS about what cases to start with”.• Methods: If the data are retrospective, then how reliable is the scoring of technicaldifficulty for procedures as mentioned in paragraph 2 of the outcomes section? This islikely meaningless as no one can really remember this unless it was gathered inprospective fashion.As stated in the discussion section, when addressing study limitations (page 11), thisanalysis carries all the drawbacks of a retrospective design. Based on your remark, wenow briefly mention this intrinsic limitation affects also the adopted scoring system(page 12): “Besides the quality of the data collection itself, the retrospective designintrinsically affected other aspects of the study methodology, including the difficultyscale used to score the procedures. This could have been much more reliable in thesetting of a prospective study”.• How did you account for patients that had surgery at a large center and did notfollowup at that center for the complication. How did you devise the cut point for youranalysis?We do not have this specific information. Every center was asked to provide thefollowup data. But we cannot provide at this time specific information about how, whereand by who were these patients followed. Again, this is another drawback that is strictlyrelated to the retrospective study design.• Results: Would be ideal to report the range for each variable presented. Nice to seethe multivariate analysis with this work.As specified in the statistical section (page 5): “Continuous variables were reported asmean (standard deviation) and categorical variables as frequency (percent)”. Thus,standard deviation (rather than range) has been used as measure of variability.• Discussion: Please further stress the patient selection piece as this appears importantand you believe that it contributed to lower complications. I think so as well so thiswould be the opportunity to help guide the urologist considering LESS on what casesand types of patient to start with. Hate to see someone read this and have their firstLESS case be an endophytic partial nephrectomy.Thanks. Based on your recommendation, this has been further stressed (page 12).

Reviewer #2:• The authors have put together a well written multi-institutional retrospective report onLESS that covers multiple different procedures. The attempt to identify risk factors thatmay increase the risk of conversion to another technique in this population is laudable.I think there is inherent biases and risk in lumping such broad categories of surgeriestogether, and this impacts the relevance of the results and conclusions. It is well knownthat each particular surgery is different and has its own inherent risks identified. Iunderstand the broader goal of trying to determine the risk of a technique such asLESS, but the small numbers make this endeavor extremely difficult. I think for thesedata to be meaningful it must be put in context to allow the reader to draw comparisonsto their experiences.We understand your concerns and criticisms. Of course, this study carries its owndrawbacks, as pointed out in the last part of the discussion section. Still, we believe itprovides some meaningful insights about the downsides of urologic LESS.• Methods: I am unclear how individual were recruited or selected to participate. Wasthere a requirement of how many articles they had published or how many cases theydid? I think it is critical to document the experience and qualifications of thoseparticipating detailing their surgical background and number of cases.Most of the surgeons/institutions worldwide that have been reporting LESS series(either in PubMed or at meetings) over the last five years have been contacted. Someof them chose not to participate. Of course, in this process, personal contacts andpreviously established connections between the institution leading the project(Cleveland Clinic) and the others played a role. Overall, almost all the names that yousee as co-authors of this paper are easily recognizable based on their records ofpublications the field.• There was no standardization among 20 institutions with different people performingthe same procedure these differences must be documented or explored to determinewhat was similar and what was different. Was the same instrumentation used for a

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LESS partial nephrectomy at one institution as another? Was there the same surgicalexperience? Were all these US patients or were some from Europe or other centerswere differences in the healthcare system can influence results?In the methods section (page 4-5) it is stated that: “Each group performed theprocedures according to its own protocols, entry criteria and techniques”. Now, weagree this can be regarded, on one side, as a drawback of the study. On the otherside, one of the key features of this study is actually to be able to provide “real life” dataoutside the constraints of a formally controlled study.• The technical difficulty scale is extremely arbitrary. What may be a "5" at one placemay be only a "3" at another with greater experience. Ideally this would be acentralized blinded assessment by one or two individuals reviewing past medicalhistory, imaging and operative tapes.This point was also raised by reviewer 1. We fully understand that this scale is arbitraryand not validated. As stated in the discussion section, when addressing studylimitations (page 11), this analysis carries all the drawbacks of a retrospective design.Based on your remark, we now briefly mention this intrinsic limitation affects also theadopted scoring system (page 12): “Besides the quality of the data collection itself, theretrospective design intrinsically affected other aspects of the study methodology,including the difficulty scale used to score the procedures”.• Why did you use estimated blood loss instead of looking at hemoglobin or hemotocritchanges? Again this is an arbitrary measure with no standardization and prone toobservational biases.The estimated blood loss is a widely used parameter when reporting surgicaloutcomes. Besides its limitations and imperfections, it can still be considered asurrogate measure of blood loss.• I wonder about the reduced port laparoscopy being only if ancillary instrumentsgreater than or equal to 5 mm? So if a 2mm or needlescopic instrument or port wasused it was not considered reduced port laparoscopy or conversion it was stillconsidered LESS?This point is clearly defined in the methods (page 5): “…and the use of ancillaryneedlescopic/mini-laparoscopic ports, which is still considered LESS.8 Addition of oneextra >5 mm trocar was considered as conversion to reduced port laparoscopy,whereas conversion from LESS to laparoscopic surgery was defined as unplannedinstallation of more than one trocar to complete the procedure”.• How was follow up to 90 determined at all facilities, phone interviews, survey? Werethe patients contacted or only included if they contacted that particular surgeon orinstitution?As also told to the reviewer 1, we do not have this specific information. Every centerwas asked to provide the followup data. But we cannot provide at this time specificinformation about how, where and by who were these patients followed. Again, this isanother drawback that is strictly related to the retrospective study design.• Results: Again I would want to know if these hospitalization rates reflect US or worldwide health systems which have different rules for in patient hospital stays.Correct. Different health care systems are involved here, each with its own regulationsand policies.• It is critical to put this information into context, I almost think you need a table ofparticipating institutions, how many cases they contributed, and what the experience isof the contributing surgeon. I don't think it is enough to say "experienced laparoscopicsurgeons" as the reader has no idea what this designation means. Looking at thenumbers there were about 58 cases per institution over 3 years, or 19 cases perinstitution per year - that is important contextual information to help gage theimplications of the presented data.We respectfully disagree this information would add significantly. The reader shouldlook at this analysis, by taking into account the relevant information provided and thelimitations already pointed out in the text.• It seems that the risks for conversions in highly selected, relatively young, healthypopulation are significant for oncologic procedures, when it is pelvic surgery, when therobot is used, and when the OR time is long and the cases are perceived as difficult bythe surgeon. Without context this tells me that LESS is not ready for universal adoptionand that urologist should beware of the potential pitfalls. I have a hard time discerningthe true impact or value to the reader of this report.We respectfully disagree with this opinion. Certainly, LESS is not universal, not forevery patient, every disease, or every surgeon. Careful patient selection is of outmostimportance. As stated in the conclusions of the present manuscript, “Besides

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facilitating future comparisons across institutions, this analysis can be useful inidentifying modifiable risk factors and ultimately in counseling patients regarding thecurrent risks of urologic LESS”. We are confident when saying that our analysis can beregarded as another landmark in the field. Not the most important one, but a majorone. Presented here is an unrestricted overview of complications and conversions inurologic LESS worldwide. With the remarkable feature of using a central reportingsystem, allowing a standardized reporting, the readers are offered a picture of whathas been done up to 2010 in different institutions world wide in a variety of settings andhealth care systems.

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Cleveland, November 2011

William D. Steers, M.D.

Editor

Anthonh J. Schaeffer, M.D.

Associate Editor

THE JOURNAL OF UROLOGY

RE: JU-11-1768. UROLOGIC LAPAROENDOSCOPIC SINGLE-SITE SURGERY (LESS):

MULTI-INSTITUTIONAL ANALYSIS OF RISK FACTORS FOR CONVERSIONS AND

POSTOPERATIVE COMPLICATIONS

Dear Editors,

We thank you once again for having considered our manuscript and we truly thank the reviewers for

their constructive comments.

Please find enclosed the revised version of the paper including the changes that have been “tracked”.

Also please find below our point-by-point reply to the reviewers.

The entire manuscript was also refined to comply with the word count limitation.

We hope you might find our manuscript now suitable for publication.

Regarding the tables 4 to 8, we elect to post them on The Journal's website at a charge of $79/page.

Warmest regards.

On behalf of all the authors,

Riccardo Autorino, MD

Jihad H. Kaouk, MD

Cover Letter

Reviewer #1:

Abstract: Only the first sentence is supported by the data presented. The idea brought out in

the second sentence should be further developed in the discussion so that the novice to LESS

would clearly know what types of patients give the highest chance of success.

We tried to further stress this in the discussion (page 12): “…this analysis is likely to

provide some guidance to the urologist novice to LESS about what cases to start with”.

Methods: If the data are retrospective, then how reliable is the scoring of technical difficulty

for procedures as mentioned in paragraph 2 of the outcomes section? This is likely

meaningless as no one can really remember this unless it was gathered in prospective

fashion.

As stated in the discussion section, when addressing study limitations (page 11), this

analysis carries all the drawbacks of a retrospective design. Based on your remark, we

now briefly mention this intrinsic limitation affects also the adopted scoring system

(page 12): “Besides the quality of the data collection itself, the retrospective design

intrinsically affected other aspects of the study methodology, including the difficulty

scale used to score the procedures. This could have been much more reliable in the

setting of a prospective study”.

How did you account for patients that had surgery at a large center and did not followup at

that center for the complication. How did you devise the cut point for your analysis?

We do not have this specific information. Every center was asked to provide the

followup data. But we cannot provide at this time specific information about how,

where and by who were these patients followed. Again, this is another drawback that is

strictly related to the retrospective study design.

Results: Would be ideal to report the range for each variable presented. Nice to see the

multivariate analysis with this work.

As specified in the statistical section (page 5): “Continuous variables were reported as

mean (standard deviation) and categorical variables as frequency (percent)”. Thus,

standard deviation (rather than range) has been used as measure of variability.

Discussion: Please further stress the patient selection piece as this appears important and

you believe that it contributed to lower complications. I think so as well so this would be the

opportunity to help guide the urologist considering LESS on what cases and types of patient

to start with. Hate to see someone read this and have their first LESS case be an endophytic

partial nephrectomy.

Thanks. Based on your recommendation, this has been further stressed (page 12).

Reviewer #2:

The authors have put together a well written multi-institutional retrospective report on LESS

that covers multiple different procedures. The attempt to identify risk factors that may

increase the risk of conversion to another technique in this population is laudable. I think

there is inherent biases and risk in lumping such broad categories of surgeries together, and

this impacts the relevance of the results and conclusions. It is well known that each particular

surgery is different and has its own inherent risks identified. I understand the broader goal of

trying to determine the risk of a technique such as LESS, but the small numbers make this

endeavor extremely difficult. I think for these data to be meaningful it must be put in context

to allow the reader to draw comparisons to their experiences.

We understand your concerns and criticisms. Of course, this study carries its own

drawbacks, as pointed out in the last part of the discussion section. Still, we believe it

provides some meaningful insights about the downsides of urologic LESS.

Methods: I am unclear how individual were recruited or selected to participate. Was there a

requirement of how many articles they had published or how many cases they did? I think it

is critical to document the experience and qualifications of those participating detailing their

surgical background and number of cases.

Most of the surgeons/institutions worldwide that have been reporting LESS series

(either in PubMed or at meetings) over the last five years have been contacted. Some of

them chose not to participate. Of course, in this process, personal contacts and

previously established connections between the institution leading the project

(Cleveland Clinic) and the others played a role. Overall, almost all the names that you

see as co-authors of this paper are easily recognizable based on their records of

publications the field.

There was no standardization among 20 institutions with different people performing the

same procedure these differences must be documented or explored to determine what was

similar and what was different. Was the same instrumentation used for a LESS partial

nephrectomy at one institution as another? Was there the same surgical experience? Were all

these US patients or were some from Europe or other centers were differences in the

healthcare system can influence results?

In the methods section (page 4-5) it is stated that: “Each group performed the

procedures according to its own protocols, entry criteria and techniques”. Now, we

agree this can be regarded, on one side, as a drawback of the study. On the other side,

one of the key features of this study is actually to be able to provide “real life” data

outside the constraints of a formally controlled study.

The technical difficulty scale is extremely arbitrary. What may be a "5" at one place may be

only a "3" at another with greater experience. Ideally this would be a centralized blinded

assessment by one or two individuals reviewing past medical history, imaging and operative

tapes.

This point was also raised by reviewer 1. We fully understand that this scale is arbitrary

and not validated. As stated in the discussion section, when addressing study limitations

(page 11), this analysis carries all the drawbacks of a retrospective design. Based on

your remark, we now briefly mention this intrinsic limitation affects also the adopted

scoring system (page 12): “Besides the quality of the data collection itself, the

retrospective design intrinsically affected other aspects of the study methodology,

including the difficulty scale used to score the procedures”.

Why did you use estimated blood loss instead of looking at hemoglobin or hemotocrit

changes? Again this is an arbitrary measure with no standardization and prone to

observational biases.

The estimated blood loss is a widely used parameter when reporting surgical outcomes.

Besides its limitations and imperfections, it can still be considered a surrogate measure

of blood loss.

I wonder about the reduced port laparoscopy being only if ancillary instruments greater than

or equal to 5 mm? So if a 2mm or needlescopic instrument or port was used it was not

considered reduced port laparoscopy or conversion it was still considered LESS?

This point is clearly defined in the methods (page 5): “…and the use of ancillary

needlescopic/mini-laparoscopic ports, which is still considered LESS.8 Addition of one

extra >5 mm trocar was considered as conversion to reduced port laparoscopy, whereas

conversion from LESS to laparoscopic surgery was defined as unplanned installation of

more than one trocar to complete the procedure”.

How was follow up to 90 determined at all facilities, phone interviews, survey? Were the

patients contacted or only included if they contacted that particular surgeon or institution?

As also told to the reviewer 1, we do not have this specific information. Every center was

asked to provide the followup data. But we cannot provide at this time specific

information about how, where and by who were these patients followed. Again, this is

another drawback that is strictly related to the retrospective study design.

Results: Again I would want to know if these hospitalization rates reflect US or world wide

health systems which have different rules for in patient hospital stays.

Correct. Different health care systems are involved here, each with its own regulations

and policies.

It is critical to put this information into context, I almost think you need a table of

participating institutions, how many cases they contributed, and what the experience is of the

contributing surgeon. I don't think it is enough to say "experienced laparoscopic surgeons"

as the reader has no idea what this designation means. Looking at the numbers there were

about 58 cases per institution over 3 years, or 19 cases per institution per year - that is

important contextual information to help gage the implications of the presented data.

We respectfully disagree this information would add significantly. The reader should

look at this analysis, by taking into account the relevant information provided and the

limitations already pointed out in the text.

It seems that the risks for conversions in highly selected, relatively young, healthy population

are significant for oncologic procedures, when it is pelvic surgery, when the robot is used,

and when the OR time is long and the cases are perceived as difficult by the surgeon. Without

context this tells me that LESS is not ready for universal adoption and that urologist should

beware of the potential pitfalls. I have a hard time discerning the true impact or value to the

reader of this report.

We respectfully disagree with this opinion. Certainly, LESS is not universal, not for

every patient, every disease, or every surgeon. Careful patient selection is of outmost

importance. As stated in the conclusions of the present manuscript, “Besides facilitating

future comparisons across institutions, this analysis can be useful in identifying

modifiable risk factors and ultimately in counseling patients regarding the current risks

of urologic LESS”. We are confident when saying that our analysis can be regarded as

another landmark in the field. Not the most important one, but a major one. Presented

here is an unrestricted overview of complications and conversions in urologic LESS

worldwide. With the remarkable feature of using a central reporting system, allowing a

standardized reporting, the readers are offered a picture of what has been done up to

2010 in different institutions world wide in a variety of settings and health care systems.

1

UROLOGIC LAPAROENDOSCOPIC SINGLE-SITE SURGERY (LESS): 1

MULTI-INSTITUTIONAL ANALYSIS OF RISK FACTORS FOR 2

CONVERSIONS AND POSTOPERATIVE COMPLICATIONS 3

4

Riccardo Autorino, Jihad H. Kaouk, Rachid Yakoubi, Koon Ho Rha, Robert J. Stein, 5

Wesley M. White, Jens-Uwe Stolzenburg, Luca Cindolo, Evangelos Liatsikos, 6

Soroush Rais-Bahrami, Alessandro Volpe, Deok Hyun Han, Ithaar H. Derweesh, 7

Seung Wook Lee, Aly M. Abdel-Karim, Anibal Branco, Francesco Greco, Mohamad Allaf, 8

Rene Sotelo, Panagiotis Kallidonis, Byong Chang Jeong, Sara Best, Wassim Bazzi, 9

Phillip Pierorazio, Salah Elsalmy, Abhay Rane, Woong Kyu Han, Bo Yang, Luigi Schips, 10

Wilson R. Molina, Paolo Fornara, Carlo Terrone, Camilo Giedelman, Joo Yong Lee, 11

Sebastien Crouzet, Georges-Pascal Haber, Lee Richstone, Sun Yinghao, Fernando J. Kim, 12

Jeffrey A. Cadeddu 13

14

From Glickman Urological & Kidney Institute, Cleveland Clinic, Cleveland, OH, USA (RA, JHK, RY, 15

RJS, GPH); Dept of Urology, Yonsei University College of Medicine, Seoul, South Korea (KHR, WKH, 16

JYL); Urology Cancer Center, University of Tennessee Medical Center, Knoxville, TN, USA (WMW); 17

Dept of Urology, University of Leipzig, Leipzig, Germany (JUS); Urology Unit, S. Pio da Pietralcina 18

Hospital, Vasto, Italy (LC, LS); Department of Urology, University of Patras, School of Medicine, Patras, 19

Greece (EL, PK); Smith Institute for Urology, The Hofstra-North Shore-LIJ School of Medicine, New 20

Hyde Park, NY, USA (LR, SRB); Department of Urology, University of Eastern Piedmont, Maggiore della 21

Carità Hospital, Novara, Italy (AV, CT); Department of Urology, Samsung Medical Center, 22

Sungkyunkwan University School of Medicine, Seoul, South Korea (DHH, BCJ); Division of Urology, 23

University of California San Diego, La Jolla, CA, USA (ID, WB); Department of Urology, Hanyang 24

University College of Medicine, Seoul, South Korea (SWL); Department of Urology, Alexandria 25

University, Alexandria, Egypt (AMAK, SE); Dept of Urology, Cruz Vermelha Hospital, Curitiba, Parana, 26

Brazil (AB); Dept of Urology and Kidney Transplantation, Martin-Luther-University, Halle/Saale, 27

Germany (FG, PF); James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, 28

Baltimore, MD, USA (MA, PP); Unidad de Urología, Instituto Médico La Floresta, Venezuela (RS, CG); 29

Deparment of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA (SB, JAC); 30

Dept of Urology, East Surrey Hospital, Redhill, Surrey, UK (AR); Dept of Urology, Changhai Hospital, 31

Shanghai, China (BY, SY); Denver Health Medical Center, University of Colorado Health Science Center, 32

Denver, CO, USA (WM, FJK); Service d'Urologie et chirurgie de la transplantation, Hôpital Edouard-33

Herriot, Lyon, France 34

35

*Manuscript (Submit in MS Word; include Title Page and Abstract; Tables and Figures should NOT be included but attached separately)

2

Corresponding author: Riccardo Autorino, MD, PhD - Glickman Urological and Kidney 1

Institute, Cleveland Clinic, Cleveland, OH, USA - Email: [email protected]; [email protected] 2

3

Word count: 2499 4

Abstract word count: 250 5

6

Running head: Conversions and complications of urologic LESS 7

8

Key words: Conversions; Complications; Laparoendoscopic single-site surgery; Multi-9

institutional; Single port laparoscopy; LESS; scarless surgery; urology 10

11

3

Abstract 1

Purpose. To analyze the incidence of and the risk factors for complications and 2

conversions in a large contemporary series of patients undergoing urologic LESS. 3

Methods. Study cohort consisted of consecutive patients treated with LESS 4

between August 2007 and December 2010 at 21 institutions. Logistic regression model 5

was used for the following analyses: risk of conversion; risk of postoperative 6

complications of any grade and of high grade only. 7

Results. One thousand one hundred and sixty three cases were included in the 8

analysis. Intraoperative complications occurred in 3.3% of cases. The overall conversion 9

rate was 19.6% with 14.6%, 4% and 1.1% converted to “reduced port” laparoscopy, 10

conventional laparoscopy/robotic and open surgery, respectively. On multivariable 11

analysis, the factors resulting to be significantly associated with risk of conversion were 12

oncologic surgical indication (p=0.02), pelvic surgery (p<0.001), robotic approach 13

(p<0.001), high difficulty score (p=0.004), extended OR time (p=0.03), and the 14

occurrence of an intraoperative complication (p=0.001). A total of 120 postoperative 15

complications occurred in 109 patients (9.4%) with major ones in just 2.4% of the entire 16

cohort. Reconstructive procedure (p=0.03), high difficulty score (p=0.002) and extended 17

OR time (p=0.02) were identified as predictors of high grade complications. 18

Conclusions. Urologic LESS can be performed with low complication rates, 19

resembling those observed in laparoscopic series. The conversion rates suggest that early 20

adopters of the technique have adhered to the principles of careful patient selection and 21

safety. Besides facilitating future comparisons across institutions, this analysis can be 22

useful in counseling patients regarding the current risks of urologic LESS. 23

24

25

4

Introduction 1

LESS has been increasingly reported in the urologic literature over the last few 2

years.1 Comparative studies have suggested that LESS is at least comparable to standard 3

laparoscopy.2, 3

However, despite a steady adoption worldwide for a wide range of 4

surgical indications,4 the actual role of LESS remains to be determined.

5 5

Similarly to what has been done for laparoscopy,6 LESS needs to be scrutinized 6

for the risk of complications. This becomes even more imperative as LESS is technically 7

more challenging due to its inherent ergonomic limitations. Although conversion cannot 8

be regarded as a complication itself, it nevertheless constitutes an important factor when 9

fully counseling patients regarding the potential risks/benefits of any given procedure.7 In 10

general, the potential for complications and the risk for conversion should be 11

appropriately low for LESS to be offered as a reasonable alternative to more established 12

techniques.8

13

To date, limited data have been reported specifically analyzing the occurrence of 14

complications and need for conversions during LESS.9-12

15

This multi-institutional project was initiated as a collaborative effort with the 16

purpose of reporting the contemporary practice of LESS at centers pioneering the 17

development of this technique in urology worldwide.4 The aim of the present study is to 18

analyze the incidence of and the risk factors for complications and conversions in a large 19

contemporary series of patients undergoing urologic LESS. 20

21

Methods 22

Study design 23

The study cohort consisted of consecutive patients treated with LESS between 24

August 2007 and December 2010 at 21 participating institutions. Groups at medical 25

centers worldwide with reported experience in urologic LESS were identified by 26

searching available literature and invited to participate in the study. Each group 27

performed the procedures according to its own protocols, entry criteria and techniques. 28

All patients were consented specifically for LESS. Raw data without any identifier were 29

retrospectively collected and gathered into a standardized datasheet. 30

Outcomes 31

5

Demographic data were accrued including age, gender, race, BMI, past history of 1

previous abdominal/pelvic surgery, ASA score, co-morbidities, and indication for LESS. 2

Procedures were categorized as “extirpative/ablative” or “reconstructive” and as 3

“upper urinary tract” or “pelvic”. Moreover they were scored by degree of technical 4

difficulty according to a scale adapted from the European Scoring System for 5

laparoscopic urologic surgery.4, 13

6

The following outcome parameters were analyzed: operative time, estimated 7

blood loss, intraoperative adverse events, transfusions, length of stay, and VAPS at 8

discharge. 9

Relevant operative data related to the surgical procedure were recorded, including 10

access technique (single-port or single-incision/single-site), access site (umbilical or 11

extra-umbilical), approach (transperitoneal or retroperitoneal), use of the da Vinci™ 12

robot, type of single-port device, and the use of ancillary needlescopic/mini-laparoscopic 13

ports, which is still considered LESS.8 Addition of one extra >5 mm trocar was 14

considered as conversion to reduced port laparoscopy, whereas conversion from LESS to 15

laparoscopic surgery was defined as unplanned installation of more than one trocar. 16

Conversion to open surgery was defined as creation of an unplanned abdominal incision. 17

Postoperative complications were graded according to the standardized Clavien-18

Dindo system.14

Both medical and surgical complications occurring within 90 days after 19

surgery were captured, including inpatient stay as well as in the outpatient setting. 20

Statistical analysis 21

Continuous variables were reported as mean (standard deviation) and categorical 22

variables as frequency (percent). A logistic regression model was used for the univariable 23

and multivariable analysis. Three different risk analyses were conducted: risk of 24

conversion (to any of the following: reduced port laparoscopy, standard laparoscopy, 25

open surgery); risk of postoperative complications of any grade and of high grade 26

(Clavien 3–5) complications only. Variables with a p value of <0.2 on univariable 27

analysis were selected for multivariable analysis. For the high-grade complications, only 28

univariable analysis was performed due to the small number of events. 29

Analyzed variables included: gender, age at surgery (<60 years and ≥ 60 years), 30

BMI (<30 kg/m2 and ≥ 30 kg/m

2), prior abdominal or pelvic surgery, ASA score (0-2 and 31

6

>2), presence of any co-morbidity, indication, surgical site (upper tract vs pelvic), access 1

site (umbilical vs extraumbilical), surgical approach (transperitoneal vs 2

retro/extraperitoneal), type of surgery (extirpative vs recontructive), use of the robotic 3

approach, procedure difficulty score (≤2 and ≥ 3), OR time (<3h and ≥ 3h), EBL ( 4

<100ml and ≥ 100 ml), and the presence of intra-operative complication. For statistical 5

analysis of risk factors in cases with more than a single complication only the highest 6

grade was considered. 7

A two-sided p < 0.05 was considered statistically significant. All statistical 8

analyses were carried out using Statistical Package for Social Sciences version 16.0 9

(SPSS Inc, Chicago, IL, USA). 10

11

Results 12

Patients and procedures 13

Overall, 1163 cases were included in the analysis (Table 1). Procedures were 14

mostly of an extirpative type (83.4%), and largely targeted the upper urinary tract 15

(85.6%). A single port technique applied via transperitoneal access was preferentially 16

adopted and the umbilicus was the most common site of access. In 12.3% of cases the 17

daVinci™ robotic platform was used. 18

Outcomes 19

Overall, mean operative room time was 155.8 (75.8) minutes and mean estimated 20

blood loss was 141 (271.5) mL. Intraoperative complications occurred in 3.3% of cases. 21

The overall conversion rate was 19.6% with 14.6%, 4% and 1.1% converted to “reduced 22

port” laparoscopy, conventional laparoscopy/robotic and open surgery, respectively. 23

Mean hospital stay was 3.5 (2.6) days with a mean VAPS at discharge of 1.5 (1.4) (Table 24

2). Conversions and complications for the most commonly performed procedures are 25

summarized in table 3. 26

Predictors of conversion (Table 4) 27

Univariable analysis demonstrated that female gender (p=0.01), oncologic 28

surgical indication (p<0.001), pelvic surgery (p<0.001), extra/retroperitoneal approach 29

(p=0.01), reconstructive procedure (p=0.003), robotic approach (p<0.001), high 30

procedure score (p<0.001), extended OR time (p<0.001), higher EBL (p<0.001) and the 31

7

occurrence of an intraoperative complication (p=0.001) were potential risk factors for 1

conversion. 2

On multivariable analysis, the only factors still resulting to be significantly 3

associated with a risk of conversion were: oncologic indication (p=0.02), pelvic surgery 4

(p<0.001), robotic approach (p<0.001), high procedure score (p=0.004), extended OR 5

time (p=0.03), and occurrence of intraoperative complication (p=0.001). 6

Analysis of postoperative complications 7

A total of 120 complications occurred in 109 patients (9.4% of the entire series). 8

As is outlined in table 2, the majority of patients experienced minor (grade 1 and 2) 9

complications with major (grade 3 and 4) ones occurring only in 2.4% of the entire cohort 10

(28/1163). There was no case of multiple-organ dysfunction (grade 4b) or death (grade 11

5). Thirty-eight different types of complications were recorded and grouped into 10 12

categories (Table 5). The most common complication categories were infectious (1.9%), 13

hemorragic (1.9%), gastrointestinal (1.8%) and genitourinary (1.7%). The most common 14

events were: ileus and transfusions due to bleeding. 15

Predictors of postoperative complications 16

Univariable analysis to evaluate predictors of any grade of complications 17

identified female gender (p=0.04), extended OR time (p=0.04) and occurrence of 18

intraoperative complication (p=0.003) as significant. At multivariable analysis female 19

gender (p=0.03) and occurrence of intraoperative complication (p=0.002) remained 20

statistically significant, whereas higher ASA score (p=0.11), reconstructive procedure 21

(p=0.17) and extended OR time trended towards significance (Table 6). 22

Regarding high grade complications only, univariable analysis identified 23

reconstructive procedure (p=0.03), high procedure score (p=0.002) and extended OR time 24

(p=0.02) as significant predictors with robotic approach (p=0.14) and higher EBL 25

(p=0.12) trending towards significance (Table 7). 26

27

Discussion 28

Until recently, only three large series of urologic LESS had been reported.15-17

29

White et al described in 2009 a single institution experience with the first 100 LESS 30

urologic procedures.15

Six patients required conversion to standard laparoscopy with no 31

8

patients requiring conversion to open surgery. The overall complication rate was 11%. A 1

bi-center experience with 100 LESS procedures was reported by Desai et al.16

The 2

addition of one or more ports was needed in six cases, and conversion to open surgery 3

was necessary in four cases. The overall conversion rate was 10% with one death 4

following simple prostatectomy. The overall complication rate was 14%. Choi et al 5

reported a cumulative experience with 171 patients undergoing LESS.17

Intraoperative 6

complications occurred in seven cases (4.1%), and postoperative complications occurred 7

in nine cases (5.3%). Conversion to mini-incision open surgery occurred in seven (4.1%) 8

cases. 9

Our group has recently reported a detailed analysis of the initial series of more 10

than 1000 LESS cases from different urologic institutions worldwide.4 The present report 11

illustrates another analysis from the same group of investigators by focusing on the 12

complications and conversions of urologic LESS. 13

Complication rates are broadly considered as surrogates of surgical competency. 14

Accurate reporting of complications is important for preoperative counseling, for 15

identifying modifiable risk factors to reduce complication rates, and for clinical trial 16

design. Even if complications and conversions have been reported in several series of 17

specific LESS procedures,1 few studies have specifically addressed the issue with LESS 18

overall as a technique. 19

Irwin et al reported a study looking at complication and conversion rates in 125 20

upper tract urologic LESS procedures from six institutions.9 Conversion to laparoscopy 21

was necessary in 7 patients (5.6%), and no patients required open conversion. 22

Complications occurred in 15.2%. The authors concluded that LESS appears to be 23

associated with higher rates of complications compared to mature laparoscopic series, but 24

conversions occur infrequently as a reflection of stringent patient selection. Limitations 25

of that study included the inability to standardize LESS patient-selection criteria, 26

instrumentation, and surgical technique as well as the lack of available complete data 27

from a control group for comparison. These limitations can be also encountered in our 28

analysis and are directly linked to its retrospective nature. Moreover, besides describing 29

the events occurring in their series, the authors did not provide a risk analysis. This was 30

more recently done by Greco et al who looked at risk factors for complications in a multi-31

9

institutional series of LESS for upper urinary tract diseases.12

The overall complication 1

rate in this series was 17% %, including conversions to open surgery accounted for as a 2

complication. Multivariable analysis showed that a higher ASA score and malignant 3

disease at pathology represented risk factors for complications. The authors concluded 4

that surgeons approaching LESS should start with benign diseases in low-surgical-risk 5

patients. 6

Best et al reviewed their initial series of LESS pyeloplasties, focusing on the 30-7

day complication rate. Seven patients (25%) experienced complications, 71% of them 8

being in the first ten cases. The authors concluded that LESS pyeloplasty is a technically 9

challenging procedure even for an experienced laparoscopic surgeon.9 Ramasamy et al. 10

compared postoperative complications of LESS and standard laparoscopic living donor 11

nephrectomy using a standardized complication reporting system.18

At 30 days there was 12

no difference in the overall complication rate between the two groups (7.1% vs 7.9%, p 13

>0.05). Multivariable binary logistic regression analysis revealed that estimated blood 14

loss was the only predictor of fewer complications.11

15

The present study is unique for two main reasons. It is performed on the largest 16

LESS series ever reported, including both upper tract and pelvic surgical procedures and 17

it provides for the first time an analysis of risk factors for both complications and 18

conversions. 19

We found an overall conversion rate of 19.7%, of which 14.6%, 4% and 1.1% 20

underwent conversion to “reduced port” laparoscopy, conventional laparoscopy and open 21

surgery, respectively. At multivariable analysis, significant factors increasing the 22

likelihood of any type of conversion included oncologic surgical indication, pelvic 23

surgery, use of robotic assistance, high procedure difficulty score, extended OR time, and 24

occurrence of intraoperative complication. Arguably, these factors are somehow 25

associated. Procedures with a higher degree of difficulty naturally require more operative 26

time. Likewise, the robotic operating platform is often employed in inherently more 27

challenging cases.18

LESS pelvic surgery has been already recognized as highly 28

challenging, and this is likely related to ergonomic considerations. As expected, the 29

occurrence of an intraoperative complication was associated with increased risk of 30

conversion. This indirectly suggests that surgeons embraced the concept that “patient 31

10

safety comes first”. And this becomes clearer when looking at the conversions for the 1

most commonly performed procedures (Table 3). Not surprisingly, partial nephrectomy 2

is by far the procedure which is more likely to be not completed as LESS. Others, each 3

for different specific issues, still represent a challenge for the surgeon embarking in 4

LESS: donor nephrectomy, because of donor safety,18

pyeloplasty, because of the need 5

for precise suturing,20

and adrenalectomy, because of anatomical topography of the 6

adrenal gland.21

7

Overall, postoperative complications were detected in 9.4% of cases with the vast 8

majority of these complications being low grade. As previously mentioned ,22

the 9

spectrum of complications for LESS would be expected to be identical to those of 10

laparoscopic surgery in addition to LESS-specific issues related to access, instruments 11

used, and limited dexterity and triangulation. When looking at the specifics of 12

complications in our series they seem to resemble those of reported laparoscopic series.23-

13

28 Statistically significant associations between the occurrence of a complication of any 14

grade were noted on multivariable analysis only for female gender and occurrence of an 15

intraoperative complication, whereas higher ASA score, reconstructive nature of the 16

procedure and extended OR time trended towards, but did not reach, statistical 17

significance. 18

Interestingly, significant factors partially differed when considering only high 19

grade complications, which represent those having a more significant clinical impact on 20

the postoperative course. In this regard, univariable analysis identified reconstructive 21

procedure, high procedure difficulty score and extended OR time as significant 22

predictors. Again, not surprisingly, the more challenging the procedure, and this 23

especially applies for those requiring suturing, the more a certain LESS technique is 24

likely to deviate from a regular postoperative course. 25

Martin et al established a list of 10 critical elements that should be included when 26

reporting surgical complications.29

The aim was to provide a more accurate and 27

comprehensive representation of surgical morbidity and to allow reliable comparisons of 28

the outcomes among different institutions, surgeons, or surgical techniques. Despite the 29

availability of such a standardized reporting methodology, it has been noted that this 30

remains underused in urologic literature.30

Notably, Martin criteria have been applied in 31

11

our analysis, including the use of a grading system to objectively measure the severity of 1

each complication. 2

The present study carries a few limitations. First, it is a retrospective study and, as 3

such, may not thoroughly capture all conversions/complications. Even if data had been 4

prospectively collected by most of the centers, biases related to the retrospective design 5

remain. Moreover, the data presented herein do not reflect total complications but rather 6

complications occurring within a defined time period after surgery. Besides the quality of 7

the data collection, the retrospective design intrinsically affected other aspects of the 8

study methodology, including the difficulty scale used to score the procedures. 9

Second, our series represents the outcomes of surgeons with an extensive 10

laparoscopic background. As such, the results may not be representative of those obtained 11

by less experienced urologists. That being stated, these same skilled surgeons were in 12

their learning curve and still in a phase of standardization of the procedures. 13

Nevertheless, this analysis is likely to provide some guidance to the urologist novice to 14

LESS about what cases to start with. 15

Third, a comparative analysis with standard laparoscopy and potentially to other 16

available scarless options, remains to be undertaken. However, when putting our findings 17

into perspective with reported large series of urologic laparoscopy, LESS appears to 18

compare favorably in terms of conversions and complications (Table 8)

22-27,31,32. 19

20

Conclusions 21

The present large multi-institutional analysis comprehensively details conversions 22

and complications of urologic LESS. In accordance with previous observations, our 23

present findings show that urologic LESS can be performed with low complication rates 24

in experienced hands, resembling those observed in major reported laparoscopic series. 25

The conversion rates suggest that early adopters of the technique have adhered to the 26

principles of careful patient selection and safety in this early phase of the development of 27

LESS. Besides facilitating future comparisons across institutions, this analysis can be 28

useful in identifying modifiable risk factors and ultimately in counseling patients 29

regarding the current risks of urologic LESS. 30

12

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1

LIST OF ABBREVIATIONS 1

- Laparo-endoscopic single-site surgery (LESS) 2

- Body Mass index (BMI) 3

- American Society of Anesthesiology (ASA) 4

- Visual analogue pain score (VAPS) 5

- Estimated blood loss (EBL) 6

- Operative Room (OR) 7

*Key of Definitions for Abbreviations (only include abbreviations used 3 times or more in manuscript)

Table 1. Overview of study population, procedures and techniques

LESS technique, n (%)

Single port

Single site

902 (77.7)

258 (22.3)

Surgical approach, n (%)

Transperitoneal

Retro/Extraperitoneal

1082 (93)

81 (7)

Access site, n (%)

Umbilical

Extraumbilical

1044 (90.5)

109 (9.5)

Legends: BMI=Body Mass Index; ASA=American Society of Anesthesiology;

LESS=Laparoendoscopic Single Site Surgery

Patients, no. 1163

Age, year, mean (SD) 51.5 (16.6)

BMI, kg/m2, mean (SD) 25.4 (6.6)

BMI, n (%)

<30

≥30

981 (86)

160 (14)

ASA score, n (%)

1 or 2

3 or 4

994 (86)

162 (14)

Comorbidity, n (%) Absent

Present

573 (49.6)

583 (50.4)

Prior Abdominal/Pelvic Surgery, n (%) Absent

Present

833 (73.3)

304 (26.7)

Surgical indication, n (%)

Non Oncologic

Oncologic

647 (55.7)

515 (44.3)

Type of Surgery, n (%)

Extirpative/ablative

Reconstructive

970 (83.4)

193 (16.6)

Procedure Score, n (%)

1 or 2

≥3

636 (56.5)

489 (43.5)

Surgery site, n (%)

Pelvic

Upper

168 (14.4)

995 (85.6)

Robotic approach, n (%)

No

Yes

1020 (87.7)

143 (12.3)

Tables

Table 2. Main outcomes

ORT, min, mean (SD) 155.8 (75.8)

EBL, ml, mean (SD) 141 (271.5)

Intraoperative complication, n (%) Absent

Present

1125 (96.7)

38 (3.3)

Conversion*, n (%)

Reduced port

Standard Lap

Open

Overall

170 (14.6)

47 (4)

13 (1.1)

230 (19.7)

LOS, days, mean (SD) 3.49 (2.6)

VAPS at discharge°, mean (SD) 1.53 (1.4)

Patients with post-operative complication^, n (%)

Grade 1

Grade 2

Grade 3

Grade 4

Overall

37 (33.9)

44 (40.4)

23 (21.1)

5 (4.6)

109

Legends: ORT=Operative room time; EBL=estimated blood loss; LOS=length of stay;

VAPS=Visual analog pain score

*Conversion to reduced port in case of only one 5 or 12 mm port added; conversion to

laparoscopy if more than 1 port added.

°scale 1 to 10

^In case of patients with >1 complications, the one with highest grade is considered here.

Table 3. Conversions and complications for the most commonly performed (>50

cases) LESS procedures

Procedure

Cases,

n

Conversions, n (%) Intraoperative

complications,

n (%)

Postoperative

complications, n

(%)

Reduced

port

Laparoscopy Open Overall All

Grades

Grade

3-4

Radical nephrectomy 220 17 (7.7) 6 (2.7) 1 (0.5) 24 (10.9) 7 (3.2) 20 (9.1) 4 (1.8)

Simple nephrectomy 147 13 (8.8) 8 (5.4) 2 (1.4) 23 (15.6) 5 (3.4) 14 (9.5) 3 (2)

Partial nephrectomy 133 70 (52.6) 9 (6.8) 2 (1.5) 81 (60.9) 6 (4.5) 13 (9.8) 4 (3)

Renal cyst decortication 128 0 (0) 2 (1.6) 0 (0) 2 (1.6) 2 (1.6) 9 (7.1) 0 (0)

Pyeloplasty 95 4 (4.2) 9 (9.5) 0 (0) 13 (13.7) 2 (2.1) 17 (17.9) 9 (9.5)

Donor nephrectomy 61 8 (13.1) 5 (8.2) 0 (0) 13 (21.3) 1 (1.6) 5 (8.2) 2 (2)

Adrenalectomy 55 7 (12.7) 6 (10.9) 0 (0) 13 (23.6) 7 (12.7) 2 (3.6) 0 (0)

Ureterolithothomy 55 0 (0) 0 (0) 3 (5.5) 3 (5.5) 1 (1.8) 5 (9.1) 0 (0)

Varicocelectomy 54 1 (1.9) 0 (0) 0 (0) 1 (1.9) 0 (0) 5 (9.3) 0 (0)

Table 4. Univariable and multivariable analysis for the risk of conversion

Variables Pts without

conversion

(n=933)

Pts with

conversion

(n=230)

Univariable analysis Multivariable analysis

OR (95% CI) p

value

OR (95% CI) p

value

Age, y, n (%)

<60

≥60

617 (66.3)

313 (33.7)

155 (67.4)

75 (32.6)

0.95 (0.70, 1.29)

0.76

Gender, n (%)

Male

Female

471 (50.5)

462 (49.5)

136 (59.1)

94 (40.9)

0.70 (0.52, 0.94)

0.01

0.71 (0.49, 1.04)

0.07

Co-morbidity, n (%)

Absent

Present

463 (49.9)

464 (50.1)

110 (48)

119 (52)

1.07 (0.80, 1.44)

0.6

ASA score, n (%)

1 or 2

3 or 4

795 (85.8)

132 (14.2)

199 (86.9)

30 (13.1)

0.90 (0.59, 1.39)

0.65

BMI, kg/m2, n (%)

<30

≥30

788 (86.3)

125 (13.7)

193 (84.6)

35 (15.4)

1.14 (0.76, 1.71)

0.51

Prior Surgery, n (%)

Absent

Present

668 (73.5)

241 (26.5)

165 (72.4)

63 (27.6)

1.05 (0.76, 1.46)

0.73

Indication, n (%)

Non Oncologic

Oncologic

587 (62.9)

346 (37.1)

68 (29.7)

161 (70.3)

4.01 (2.93, 5.49)

<0.001

1.68 (1.08, 2.62)

0.02

Surgical site, n (%)

Upper

Pelvic

779 (83.5)

154 (16.5)

216 (93.9)

14 (6.1)

0.32 (0.18, 0.57)

<0.001

0.12 (0.05, 0.26)

<0.001

Access site, n (%)

Umbilical

Extraumbilical

835 (90.5)

88 (9.5)

209 (90.9)

21 (9.1)

0.95 (0.57, 1.57)

0.85

Approach, n (%)

Transperitoneal

Retro/Extraperitoneal

859 (92.1)

74 (7.9)

223 (97)

7 (3)

0.36 (0.16, 0.80)

0.01

0.67 (0.27, 1.69)

0.4

Surgery, n (%)

Extirpative/ablative

Recontructive

763 (81.8)

170 (18.2)

207 (90)

23 (10)

0.49 (0.31, 0.79)

0.003

0.76 (0.39, 1.45)

0.41

Robotic, n (%)

No

Yes

880 (94.3)

53 (5.7)

140 (60.9)

90 (39.1)

10.67 (7.27, 15.66)

<0.001

8.93 (5.29, 15.07)

<0.001

Procedure score, n

(%)

1 or 2

≥3

560 (62.3)

339 (37.7)

76 (33.6)

150 (66.4)

3.26 (2.39, 4.43)

<0.001

1.79 (1.19, 2.69)

0.004

ORT, hours, n (%)

<3

≥3

608 (67.9)

287 (32.1)

99 (45.2)

120 (54.8)

2.56 (1.90, 3.46)

<0.001

1.52 (1.02, 2.25)

0.03

EBL, ml, n (%)

<100

≥100

528 (58.3)

377 (41.7)

75 (34.6)

142 (65.4)

2.65 (1.94, 3.61)

<0.001

1.27 (0.86, 1.88)

0.22

Intra-op.

complication, n (%)

Absent

Present

911 (97.6)

22 (2.4)

214 (93)

16 (7)

3.09 (1.59, 5.99)

0.001

3.56 (1.67, 7.56)

0.001

Legend: ASA=American Society of Anesthesiology; BMI=Body Mass Index; ORT=Operative room time; EBL=estimated blood loss

Table 5. Summary of postoperative complications

Category (% of total) Complication (n=120) Frequency

Infectious (1.9%; n= 22)

Urinary tract infection 8

Sepsis 3

Fever* 9

Pelvic abscess 1

Perirenal abscess 1

Bleeding (1.9%; n= 23)

Bleeding 6

Transfusion** 14

Perirenal hematoma 3

Gastrointestinal (1.8%; n= 21)

Ileus° 17

Constipation°° 1

Acute gastritis 1

Bowel obstruction with resection 1

Recto-urethral Fistula 1

Genitourinary (1.7%; n = 20)

Acute renal failure^ 5

Urine leak 3

Urinoma^^ 2

Ureteral obstruction 3

Ureteral stenosis 1

Urethral stenosis 1

Hematuria 2

Clot Retention 1

Ureteral stent migration 2

Wound (1.3%; n=16)

Wound infection 5

Wound hematoma 2

Wound seroma 1

Wound dehiscence 4

Hernia 4

Thrombo-embolic (0.4%; n= 5)

Deep Venus Thrombosis 3

Pulmonary embolism 2

Pulmonary (0.1%; n= 2)

Pneumonia 1

Pleural edema 1

Neurological (0.1%; n=2)

Stroke 1

Syncope 1

Musculo-skeletical (0.1%; n= 2)

Ankle swelling 1

Deltoid muscle neuropraxia 1

Others (0.6%; n = 7)

Retained sponge 1

Fluid collection 2

Pain 4

n=number of patients within that category; patients experiencing complications in different categories

counted more than once.

Definition of complications: *>38°C for >2 days with unexplained origin; **In absence of symptoms,

postoperative transfusion usually indicated for Hb level <8 g/l; °defined as post operative nausea or

vomiting associated with abdominal distension requiring cessation of oral intake and intravenous fluid

support and/or nasogastric tube placement; °°defined as inability to have a bowel movement with no signs

of ileus or small bowel obstruction; ^Postoperative serum creatinine >1.5mg/dl in a patient with normal

preoperative serum creatinine; ^^Evidence of extravasation on imaging or fluid collection consistent with a

urinoma or drain fluid creatinine >1.5 mg/dl.

Table 6. Univariable and multivariable analysis for incidence of any complication

Legends: ASA=American Society of Anesthesiology; BMI=Body Mass Index; ORT=Operative room time; EBL=estimated blood loss

Variables

Pts without

complication

(n=1053)

Pts with

complication

(n=109)

Univariable analysis Multivariable analysis

OR (95% CI) p

value

OR (95% CI) p

value

Age, years, n (%)

<60

≥60

701 (66.8)

349 (33.2)

71 (65.1)

38 (34.9)

0.93 (0.61, 1.40)

0.73

Gender, n (%)

Male

Female

494 (46.9)

559 (53.1)

62 (56.9)

47 (43.1)

1.49 (1.00, 2.22)

0.04

1.54 (1.02, 2.33)

0.03

Co-morbidity, n (%)

Absent

Present

514 (49.1)

532 (50.9)

59 (54.1)

50 (45.9)

0.81 (0.55, 1.21)

0.32

ASA score, n (%)

1 or 2

3 or 4

904 (86.4)

142 (13.6)

89 (81.7)

20 (18.3)

1.43 (0.85, 2.39 )

0.17

1.53 (0.90, 2.61)

0.11

BMI, kg/m2

<30

≥30

888 (86)

145 (14)

92 (86)

15 (14)

0.99 (0.56, 1.77)

0.99

Prior Surgery, n (%)

Absent

Present

753 (73.1)

277 (26.9)

79 (74.5)

27 (25.5)

0.92 (0.85, 1.46)

0.75

Indication, n (%)

Non Oncologic

Oncologic

584 (55.5)

468 (44.5)

62 (56.9)

47 (43.1)

0.94 (0.63, 1.40)

0.78

Surgical site, n (%)

Upper

Pelvic

900 (85.5)

153 (14.5)

94 (86.2)

15 (13.8)

0.93 (0.53, 1.66)

0.82

Access site, n (%)

Umbilical

Extraumbilical

947 (90.6)

98 (9.4)

96 (89.7)

11 (10.3)

0.90 (0.40, 2.02)

0.76

Approach, n (%)

Trans

Retro/Extra

979 (93)

74 (7)

102 (93.6)

7 (6.4)

1.10 (0.57, 2.13)

0.81

Type of Surgery, n (%)

Extirpative/ablative

Recontructive

884 (84)

169 (16)

85 (78)

24 (22)

1.47 (0.91, 2.39)

0.11

1.43 (0.85, 2.41)

0.17

Robotic, n (%)

No

Yes

920 (87.4)

133 (12.6)

99 (90.8)

10 (9.2)

0.69 (0.35, 1.37)

0.29

Procedure score, n (%)

1 or 2

≥3

580 (56.6)

440 (43.1)

56 (53.3)

49 (46.7)

1.15 (0.77, 1.72)

0.48

ORT, hours

<3

≥3

649 (64.4)

358 (35.6)

58 (54.7)

48 (45.3)

1.50 (1.00, 2.24)

0.04

1.39 (0.92, 2.10)

0.11

EBL, ml

<100

≥100

548 (54.1)

465 (45.9)

55 (50.5)

54 (49.5)

1.15 (0.77, 1.71)

0.46

Intra-operative complication, n (%)

Absent

Present

1024 (97.2)

29 (2.6)

100 (91.7)

9 (8.3)

3.17 (1.46, 6.90)

0.003

3.34 (1.51, 7.35)

0.002

Table 7. Univariable analysis for incidence of high grade complication

Legends: ASA=American Society of Anesthesiology; BMI=Body Mass Index; ORT=Operative room time;

EBL=estimated blood loss

Variables Pts with

grade 0–2

complications

(n=1135)

Patients with

grade 3–4

complications

(n=28)

Univariable analysis

OR (95% CI) p value

Age, years, n (%)

<60

≥60

753 (66.5)

379 (33.5)

19 (67.9)

9 (32.1)

0.94 (0.42, 2.10)

0.88

Gender, n (%)

Male

Female

595 (52.4)

540 (47.6)

12 (42.9)

16 (57.1)

1.46 (0.68, 3.13)

0.31

Co-morbidity, n (%)

Absent

Present

558 (49.5)

570 (50.5)

15 (53.6)

13 (46.4)

0.84 (0.40, 1.79)

0.66

ASA score, n (%)

1 or 2

3 or 4

972 (86.2)

156 (13.8)

22 (78.6)

6 (21.4)

1.69 (0.67, 4.25)

0.25

BMI, kg/m2, n (%)

<30

≥30

959 (86.1)

155 (13.9)

22 (81.5)

5 (18.5)

1.40 (0.52, 3.76)

0.49

Prior Surgery, n (%)

Absent

Present

815 (73.5)

294 (26.5)

18 (64.3)

10 (35.7)

1.54 (0.70, 3.37)

0.28

Indication, n (%)

Non Oncologic

Oncologic

633 (55.8)

501 (44.2)

14 (50)

14 (50)

1.26 (0.59, 2.67)

0.54

Surgical site, n (%)

Upper

Pelvic

971 (85.6)

164 (14.4)

24 (85.7)

4 (14.3)

0.98 (0.33, 2.88)

0.98

Access site, n (%)

Umbilical

Extraumbilical

1017 (90.4)

108 (9.6)

27 (96.4)

1 (3.6)

0.34 (0.04, 2.59)

0.3

Approach, n (%)

Transperitoneal

Retro/Extraperitoneal

1055 (93)

80 (7)

27 (96.4)

1 (3.6)

0.48 (0.06, 3.64)

0.48

Type of Surgery, n (%)

Extirpative/ablative

Reconstructive

951 (83.8)

184 (16.2)

19 (67.9)

9 (32.1)

2.44 (1.09, 5.49)

0.03

Robotic, n (%)

No

Yes

998 (87.9)

137 (12.1)

22 (78.6)

6 (21.4)

1.98 (0.79, 4.98)

0.14

Procedure score, n (%)

1 or 2

≥3

629 (57.3)

469 (42.7)

7 (25.9)

20 (74.1)

3.83 (1.60, 9.13)

0.002

ORT, hours, n (%)

<3

≥3

699 (64.2)

390 (35.8)

8 (32)

17 (68)

3.80 (1.62, 8, 90)

0.002

EBL, ml, n (%)

<100 ml

≥100 ml

592 (54.1)

502 (45.9)

11 (39.3)

17 (60.7)

1.82 (0.84, 3.92)

0.12

Intra-op. complication, n (%)

Absent

Present

1099 (96.8)

36 (3.2)

26 (92.9)

2 (7.1)

2.34 (0.53, 10.27 )

0.25

Table 8. Conversions and complications in large (>1000 cases) LESS and laparoscopy series in urology

Reference Technique Time

frame

Setting Cases,

n

Intraop. complications,

n (%)

Postop. complications,

n (%)

Conversions,

n (%)

Inoue LS 1991-2009 Single institution 1017 37 (3.6) 111 (10.9) 20 (1.9)^

Fehlenkamp LS 1992-1998 Multi-institutional 2407 107 (4.4) na

Vallencien LS 1992-2001 Single institution 1311 34 (3.6) 250 (19) (1.2)

Permpongkosol LS 1993-2005 Single institution 2775 130 (4.7) 484 (17.4) 74 (2.7)^

Richstone LS 1993-2005 Single institution 2128 na na 68 (3.2)^

Soulie LS 1994-2000 Multi-institutional 1075 15 (1.4) 60 (5.6) 23 (2.1)^

Rowley LS+HALS 1996-2009 Single institution 1592 na na 20 (1.3)^

Colombo LS 1997-2006 Single institution 1867 67 (3.5) 166 (8.9) 18 (0.9)^

Present study LESS 2007-2010 Multi-institutional 1163 38 (3.3) 109 (9.3) 60 (5.1)*

Legend: LS=Laparoscopic surgery; HALS=Hand assisted Laparoscopic surgery; LESS=Laparoendoscopic single site surgery

^to open surgery

*to laparoscopic or open surgery

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