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Figure 1.
PRISMA Diagram
PRISMA Diagram

The flowchart shows the literature search and study selection process according to the PRISMA guidelines.

Figure 2.
Forest Plots of the Primary Outcomes
Forest Plots of the Primary Outcomes

Circumferential resection margin involvement was defined as 1 mm or less. Noncomplete mesorectal excision included incomplete or nearly complete resections. Risk ratios (RRs) and 95% CIs were calculated using the random-effects Mantel-Haenszel method. LRR indicates laparoscopic rectal resection; ORR, open rectal resection. Different size markers indicate weight.

Figure 3.
Forest Plots of Secondary Outcomes
Forest Plots of Secondary Outcomes

Risk ratios (RRs) and 95% CIs were calculated using the random-effects Mantel-Haenszel method. Mean difference data and 95% CIs were calculated using random-effects inverse variance weighting. LRR indicates laparoscopic rectal resection; ORR, open rectal resection. Different size markers indicate weight.

Table.  
Summary of the Included Randomized Clinical Trials
Summary of the Included Randomized Clinical Trials
1.
Siegel  R, Ma  J, Zou  Z, Jemal  A.  Cancer statistics, 2014.  CA Cancer J Clin. 2014;64(1):9-29.PubMedGoogle ScholarCrossref
2.
Ferlay  J, Soerjomataram  I, Dikshit  R,  et al.  Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012.  Int J Cancer. 2015;136(5):E359-E386.PubMedGoogle ScholarCrossref
3.
Ferlay  J, Steliarova-Foucher  E, Lortet-Tieulent  J,  et al.  Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012.  Eur J Cancer. 2013;49(6):1374-1403.PubMedGoogle ScholarCrossref
4.
American Cancer Society. Cancer facts and figures 2014. Atlanta, GA: American Cancer Society; 2014. http://www.cancer.org/acs/groups/content/@research/documents/webcontent/acspc-042151.pdf. Accessed July 2016.
5.
De Caluwé  L, Van Nieuwenhove  Y, Ceelen  WP.  Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer.  Cochrane Database Syst Rev. 2013;(2):CD006041.PubMedGoogle Scholar
6.
Quirke  P, Steele  R, Monson  J,  et al; MRC CR07/NCIC-CTG CO16 Trial Investigators; NCRI Colorectal Cancer Study Group.  Effect of the plane of surgery achieved on local recurrence in patients with operable rectal cancer: a prospective study using data from the MRC CR07 and NCIC-CTG CO16 randomised clinical trial.  Lancet. 2009;373(9666):821-828.PubMedGoogle ScholarCrossref
7.
Kusters  M, Marijnen  CA, van de Velde  CJ,  et al.  Patterns of local recurrence in rectal cancer; a study of the Dutch TME trial.  Eur J Surg Oncol. 2010;36(5):470-476.PubMedGoogle ScholarCrossref
8.
Nagtegaal  ID, Quirke  P.  What is the role for the circumferential margin in the modern treatment of rectal cancer?  J Clin Oncol. 2008;26(2):303-312.PubMedGoogle ScholarCrossref
9.
Birbeck  KF, Macklin  CP, Tiffin  NJ,  et al.  Rates of circumferential resection margin involvement vary between surgeons and predict outcomes in rectal cancer surgery.  Ann Surg. 2002;235(4):449-457.PubMedGoogle ScholarCrossref
10.
García-Granero  E, Faiz  O, Muñoz  E,  et al.  Macroscopic assessment of mesorectal excision in rectal cancer: a useful tool for improving quality control in a multidisciplinary team.  Cancer. 2009;115(15):3400-3411.PubMedGoogle ScholarCrossref
11.
Trakarnsanga  A, Gonen  M, Shia  J,  et al.  What is the significance of the circumferential margin in locally advanced rectal cancer after neoadjuvant chemoradiotherapy?  Ann Surg Oncol. 2013;20(4):1179-1184.PubMedGoogle ScholarCrossref
12.
Augestad  KM, Lindsetmo  RO, Reynolds  H,  et al.  International trends in surgical treatment of rectal cancer.  Am J Surg. 2011;201(3):353-357.PubMedGoogle ScholarCrossref
13.
van der Pas  MH, Haglind  E, Cuesta  MA,  et al; COlorectal cancer Laparoscopic or Open Resection II (COLOR II) Study Group.  Laparoscopic versus open surgery for rectal cancer (COLOR II): short-term outcomes of a randomised, phase 3 trial.  Lancet Oncol. 2013;14(3):210-218.PubMedGoogle ScholarCrossref
14.
Kang  SB, Park  JW, Jeong  SY,  et al.  Open versus laparoscopic surgery for mid or low rectal cancer after neoadjuvant chemoradiotherapy (COREAN trial): short-term outcomes of an open-label randomised controlled trial.  Lancet Oncol. 2010;11(7):637-645.PubMedGoogle ScholarCrossref
15.
Guillou  PJ, Quirke  P, Thorpe  H,  et al; MRC CLASICC Trial Group.  Short-term endpoints of conventional versus laparoscopic-assisted surgery in patients with colorectal cancer (MRC CLASICC trial): multicentre, randomised controlled trial.  Lancet. 2005;365(9472):1718-1726.PubMedGoogle ScholarCrossref
16.
Zhao  JK, Chen  NZ, Zheng  JB, He  S, Sun  XJ.  Laparoscopic versus open surgery for rectal cancer: Results of a systematic review and meta-analysis on clinical efficacy.  Mol Clin Oncol. 2014;2(6):1097-1102.PubMedGoogle Scholar
17.
Vennix  S, Pelzers  L, Bouvy  N,  et al.  Laparoscopic versus open total mesorectal excision for rectal cancer.  Cochrane Database Syst Rev. 2014;(4):CD005200.PubMedGoogle Scholar
18.
Xiong  B, Ma  L, Zhang  C.  Laparoscopic versus open total mesorectal excision for middle and low rectal cancer: a meta-analysis of results of randomized controlled trials.  J Laparoendosc Adv Surg Tech A. 2012;22(7):674-684.PubMedGoogle ScholarCrossref
19.
Arezzo  A, Passera  R, Salvai  A,  et al.  Laparoscopy for rectal cancer is oncologically adequate: a systematic review and meta-analysis of the literature.  Surg Endosc. 2015;29(2):334-348.PubMedGoogle ScholarCrossref
20.
Fleshman  J, Branda  M, Sargent  DJ,  et al.  Effect of laparoscopic-assisted resection vs open resection of stage II or III rectal cancer on pathologic outcomes: the ACOSOG Z6051 randomized clinical trial.  JAMA. 2015;314(13):1346-1355.PubMedGoogle ScholarCrossref
21.
Stevenson  AR, Solomon  MJ, Lumley  JW,  et al; ALaCaRT Investigators.  Effect of laparoscopic-assisted resection vs open resection on pathological outcomes in rectal cancer: the ALaCaRT randomized clinical trial.  JAMA. 2015;314(13):1356-1363.PubMedGoogle ScholarCrossref
22.
Moher  D, Liberati  A, Tetzlaff  J, Altman  DG, Group  P; PRISMA Group.  Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.  Int J Surg. 2010;8(5):336-341.PubMedGoogle ScholarCrossref
23.
Nagtegaal  ID, van de Velde  CJ, van der Worp  E, Kapiteijn  E, Quirke  P, van Krieken  JH; Cooperative Clinical Investigators of the Dutch Colorectal Cancer Group.  Macroscopic evaluation of rectal cancer resection specimen: clinical significance of the pathologist in quality control.  J Clin Oncol. 2002;20(7):1729-1734.PubMedGoogle ScholarCrossref
24.
Higgins  JP, Altman  DG, Gøtzsche  PC,  et al; Cochrane Bias Methods Group; Cochrane Statistical Methods Group.  The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials.  BMJ. 2011;343:d5928.PubMedGoogle ScholarCrossref
25.
Guyatt  GH, Oxman  AD, Vist  GE,  et al; GRADE Working Group.  GRADE: an emerging consensus on rating quality of evidence and strength of recommendations.  BMJ. 2008;336(7650):924-926.PubMedGoogle ScholarCrossref
26.
Hozo  SP, Djulbegovic  B, Hozo  I.  Estimating the mean and variance from the median, range, and the size of a sample.  BMC Med Res Methodol. 2005;5:13.PubMedGoogle ScholarCrossref
27.
Higgins  JP, Green  S, eds. The Cochrane Handbook for Systematic Reviews of Interventions, Version 5.1.0. http://handbook.cochrane.org. Updated March 2011. Accessed January 7, 2017.
28.
Harbour  R, Miller  J.  A new system for grading recommendations in evidence based guidelines.  BMJ. 2001;323(7308):334-336.PubMedGoogle ScholarCrossref
29.
Higgins  JP, Thompson  SG, Deeks  JJ, Altman  DG.  Measuring inconsistency in meta-analyses.  BMJ. 2003;327(7414):557-560.PubMedGoogle ScholarCrossref
30.
Ng  SS, Lee  JF, Yiu  RY,  et al.  Laparoscopic-assisted versus open total mesorectal excision with anal sphincter preservation for mid and low rectal cancer: a prospective, randomized trial.  Surg Endosc. 2014;28(1):297-306.PubMedGoogle ScholarCrossref
31.
Liang  X, Hou  S, Liu  H,  et al.  Effectiveness and safety of laparoscopic resection versus open surgery in patients with rectal cancer: a randomized, controlled trial from China.  J Laparoendosc Adv Surg Tech A. 2011;21(5):381-385.PubMedGoogle ScholarCrossref
32.
Liu  FL, Lin  JJ, Ye  F, Teng  LS.  Hand-assisted laparoscopic surgery versus the open approach in curative resection of rectal cancer.  J Int Med Res. 2010;38(3):916-922.PubMedGoogle ScholarCrossref
33.
Ng  SS, Leung  KL, Lee  JF, Yiu  RY, Li  JC, Hon  SS.  Long-term morbidity and oncologic outcomes of laparoscopic-assisted anterior resection for upper rectal cancer: ten-year results of a prospective, randomized trial.  Dis Colon Rectum. 2009;52(4):558-566.PubMedGoogle ScholarCrossref
34.
Luján  J, Valero  G, Hernandez  Q, Sanchez  A, Frutos  MD, Parrilla  P.  Randomized clinical trial comparing laparoscopic and open surgery in patients with rectal cancer.  Br J Surg. 2009;96(9):982-989.PubMedGoogle ScholarCrossref
35.
Ng  SS, Leung  KL, Lee  JF,  et al.  Laparoscopic-assisted versus open abdominoperineal resection for low rectal cancer: a prospective randomized trial.  Ann Surg Oncol. 2008;15(9):2418-2425.PubMedGoogle ScholarCrossref
36.
Pechlivanides  G, Gouvas  N, Tsiaoussis  J,  et al.  Lymph node clearance after total mesorectal excision for rectal cancer: laparoscopic versus open approach.  Dig Dis. 2007;25(1):94-99.PubMedGoogle ScholarCrossref
37.
Braga  M, Frasson  M, Vignali  A, Zuliani  W, Capretti  G, Di Carlo  V.  Laparoscopic resection in rectal cancer patients: outcome and cost-benefit analysis.  Dis Colon Rectum. 2007;50(4):464-471.PubMedGoogle ScholarCrossref
38.
Araujo  SE, da Silva eSousa  AH  Jr, de Campos  FG,  et al.  Conventional approach x laparoscopic abdominoperineal resection for rectal cancer treatment after neoadjuvant chemoradiation: results of a prospective randomized trial.  Rev Hosp Clin Fac Med Sao Paulo. 2003;58(3):133-140.PubMedGoogle Scholar
39.
Parfitt  JR, Driman  DK.  The total mesorectal excision specimen for rectal cancer: a review of its pathological assessment.  J Clin Pathol. 2007;60(8):849-855.PubMedGoogle ScholarCrossref
40.
Dworak  O, Keilholz  L, Hoffmann  A.  Pathological features of rectal cancer after preoperative radiochemotherapy.  Int J Colorectal Dis. 1997;12(1):19-23.PubMedGoogle ScholarCrossref
41.
Al-Sukhni  E, Attwood  K, Gabriel  E, Nurkin  SJ.  Predictors of circumferential resection margin involvement in surgically resected rectal cancer: a retrospective review of 23,464 patients in the US National Cancer Database.  Int J Surg. 2016;28:112-117.PubMedGoogle ScholarCrossref
42.
Martijnse  IS, Dudink  RL, West  NP,  et al.  Focus on extralevator perineal dissection in supine position for low rectal cancer has led to better quality of surgery and oncologic outcome.  Ann Surg Oncol. 2012;19(3):786-793.PubMedGoogle ScholarCrossref
43.
West  NP, Finan  PJ, Anderin  C, Lindholm  J, Holm  T, Quirke  P.  Evidence of the oncologic superiority of cylindrical abdominoperineal excision for low rectal cancer.  J Clin Oncol. 2008;26(21):3517-3522.PubMedGoogle ScholarCrossref
44.
Nagtegaal  ID, Marijnen  CA, Kranenbarg  EK, van de Velde  CJ, van Krieken  JH; Pathology Review Committee; Cooperative Clinical Investigators.  Circumferential margin involvement is still an important predictor of local recurrence in rectal carcinoma: not one millimeter but two millimeters is the limit.  Am J Surg Pathol. 2002;26(3):350-357.PubMedGoogle ScholarCrossref
45.
Tilney  HS, Rasheed  S, Northover  JM, Tekkis  PP.  The influence of circumferential resection margins on long-term outcomes following rectal cancer surgery.  Dis Colon Rectum. 2009;52(10):1723-1729.PubMedGoogle ScholarCrossref
46.
de’Angelis  N, Lizzi  V, Azoulay  D, Brunetti  F.  Robotic vs laparoscopic right colectomy for colon cancer: analysis of the initial simultaneous learning curve of a surgical fellow.  J Laparoendosc Adv Surg Tech A. 2016;26(11):882-892.PubMedGoogle ScholarCrossref
47.
Ahmed  J, Nasir  M, Flashman  K, Khan  J, Parvaiz  A.  Totally robotic rectal resection: an experience of the first 100 consecutive cases.  Int J Colorectal Dis. 2016;31(4):869-876.PubMedGoogle ScholarCrossref
48.
de’Angelis  N, Portigliotti  L, Azoulay  D, Brunetti  F.  Robotic surgery: a step forward in the wide spread of minimally invasive colorectal surgery.  J Minim Access Surg. 2015;11(4):285-286.PubMedGoogle ScholarCrossref
49.
de’Angelis  N, Portigliotti  L, Brunetti  F.  Robot-assisted rectal cancer surgery deserves a fair trial.  Colorectal Dis. 2015;17(9):824-825.PubMedGoogle ScholarCrossref
50.
Araujo  SE, Seid  VE, Klajner  S.  Robotic surgery for rectal cancer: current immediate clinical and oncological outcomes.  World J Gastroenterol. 2014;20(39):14359-14370.PubMedGoogle ScholarCrossref
51.
Baik  SH, Ko  YT, Kang  CM,  et al.  Robotic tumor-specific mesorectal excision of rectal cancer: short-term outcome of a pilot randomized trial.  Surg Endosc. 2008;22(7):1601-1608.PubMedGoogle ScholarCrossref
52.
Collinson  FJ, Jayne  DG, Pigazzi  A,  et al.  An international, multicentre, prospective, randomised, controlled, unblinded, parallel-group trial of robotic-assisted versus standard laparoscopic surgery for the curative treatment of rectal cancer.  Int J Colorectal Dis. 2012;27(2):233-241.PubMedGoogle ScholarCrossref
53.
de’Angelis  N, Portigliotti  L, Azoulay  D, Brunetti  F.  Transanal total mesorectal excision for rectal cancer: a single center experience and systematic review of the literature.  Langenbecks Arch Surg. 2015;400(8):945-959.PubMedGoogle ScholarCrossref
54.
Deijen  CL, Velthuis  S, Tsai  A,  et al.  COLOR III: a multicenter randomized clinical trial comparing transanal TME vs laparoscopic TME for mid and low rectal cancer.  Surg Endosc. 2016;30(8):3210-3215.PubMedGoogle ScholarCrossref
Original Investigation
April 19, 2017

Pathologic Outcomes of Laparoscopic vs Open Mesorectal Excision for Rectal CancerA Systematic Review and Meta-analysis

Author Affiliations
  • 1Department of Digestive, Hepatobiliary Surgery and Liver Transplantation, Henri Mondor University Hospital, Assistance Publique–Hôpitaux de Paris (AP-HP), Université Paris Est–Créteil, Créteil, France
  • 2Department of General and Digestive Surgery, Hospital Universitario Doctor Peset, Valencia, Spain
  • 3Rothschild Hospital, AP-HP, Université Paris 7, Paris, France
 

Copyright 2017 American Medical Association. All Rights Reserved.

JAMA Surg. 2017;152(4):e165665. doi:10.1001/jamasurg.2016.5665
Key Points

Question  What are the pathologic outcomes of laparoscopic rectal resection compared with open rectal resection for rectal cancer?

Finding  Based on this systematic review and meta-analysis of 14 randomized clinical trials, the risk of achieving a noncomplete (incomplete or nearly complete) mesorectal excision is significantly higher in patients undergoing laparoscopic compared with open rectal resections.

Meaning  These pathologic findings challenge the oncologic safety of laparoscopy for the treatment of rectal cancer.

Abstract

Importance  Rectal resection with mesorectal excision is the mainstay treatment for rectal cancer.

Objective  To review and analyze the evidence concerning the pathologic outcomes of laparoscopic (LRR) vs open (ORR) rectal resection for rectal cancer.

Data Sources  The Cochrane Central Register of Controlled Trials, MEDLINE (through PubMed), EMBASE, Scopus databases, and clinicaltrials.gov were searched for randomized clinical trials (RCTs) comparing LRR vs ORR.

Study Selection  Only RCTs published in English from January 1, 1995, to June 30, 2016, that compared LRR with ORR for histologically proven rectal cancer in adult patients and reported pathologic outcomes (eg, positive circumferential resection margin, and complete mesorectal excision) were eligible for inclusion. Of 369 records screened, 14 RCTs were selected for the qualitative and quantitative analyses.

Data Extraction and Synthesis  Two independent reviewers performed the study selection and quality assessment. Random-effects models were used to summarize the risk ratio (RR) and mean differences.

Main Outcomes and Measures  The rate of positive circumferential resection margin (CRM), defined as 1 mm or less from the closest tumor to the cut edge of the tissue, and the quality of mesorectal excision (complete, nearly complete, or incomplete).

Results  The meta-analysis included 14 unique RCTs with 4034 unique patients. Of 2989 patients undergoing rectal resection, a positive CRM was found in 135 (7.9%) of 1697 patients undergoing LRR and 79 (6.1%) of 1292 patients undergoing ORR (RR, 1.17; 95% CI, 0.89-1.53; P = .26; I2 = 0%) in 9 studies. A noncomplete (nearly complete and incomplete) mesorectal excision was reported in 179 (13.2%) of 1354 patients undergoing LRR and 104 (10.4%) of 998 patients undergoing ORR (RR, 1.31; 95% CI, 1.05-1.64; P = .02; I2 = 0%) in 5 studies. The distal resection margin involvement (RR, 1.12; 95% CI, 0.34-3.67; P = .86), the mean number of lymph nodes retrieved (mean difference, 0.05; 95% CI, −0.77 to 0.86; P = .91), the mean distance to the distal margin (mean difference, 0.01 cm; 95% CI, −0.12 to 0.15 cm; P = .87), and the mean distance to radial margins (mean difference, −0.67 mm; 95% CI, −2.16 to 0.83 mm; P = .38) were not significantly different between LRR and ORR. The risk for bias was assessed as low in 10 studies, high in 3, and unknown in 1. The overall quality of the evidence emerging from the literature was rated as high.

Conclusions and Relevance  Based on the available evidence, the risk for achieving a noncomplete mesorectal excision is significantly higher in patients undergoing LRR compared with ORR. These findings question the oncologic safety of laparoscopy for the treatment of rectal cancer. However, long-term results of the ongoing RCTs are awaited to assess whether these pathologic results have an effect on disease-free and overall patient survival.

Introduction

Colorectal cancers are the third most common malignant tumors worldwide.1-3 In particular, rectal cancers constitute one-third of these tumors and account for nearly 40 000 new cases per year in the United States.4

The mainstay treatment for rectal cancer remains surgical resection, for which outcomes have markedly improved during the last 20 years, mostly owing to the introduction of total mesorectal excision (TME). This surgical technique demonstrated reductions in tumor recurrence because the radial spread of cancer cells is resected entirely with the complete removal of the mesorectal tissues. Radiotherapy and chemotherapy also have major roles in the management of locally advanced rectal cancer.5

In the era of TME, the accuracy and safety of mesorectal dissection and the achievement of free resection margins are considered the most important pathologic outcomes used to measure the quality of surgery. Indeed, negative circumferential resection margin (CRM) and complete TME are associated with lower local and distal recurrence rates and better long-term survival.6-10 A recent study of a cohort of 563 patients with locally advanced rectal cancer who were treated with neoadjuvant chemoradiotherapy and surgery found that the 5-year local recurrence-free survival was 66% in patients with a CRM of 1 mm or less and 98% in patients with a CRM of greater than 1 mm.11 In another recent study evaluating achievement of complete mesorectal excision, the estimated 3-year local recurrence rate was 4% for complete, 7% for nearly complete, and 13% for incomplete mesorectal excision.6

Although minimally invasive rectal excision has been regarded as one of the most complex operations in the field of colorectal surgery, laparoscopy is a widespread technique performed by more than 70% of experienced colorectal surgeons worldwide and more than 80% in the United States.12 Large randomized clinical trials (RCTs) showed that laparoscopic TME is associated with less blood loss, earlier return of bowel movement, and shorter length of hospital stay compared with open surgery.13-15 These short-term benefits of laparoscopy were confirmed in previous meta-analyses,16-19 which found no difference in terms of overall survival, disease-free survival, and pathologic outcomes between the laparoscopic and open approaches.19 Thus, evidence appears to support laparoscopic TME as a valuable, safe, and feasible alternative to open TME, but the 2 most recent RCTs20,21 (not included in the previously published meta-analyses) found contradictory results and opened the existing conclusions to debate.

In this study, we conducted a new systematic review and meta-analysis of RCTs comparing laparoscopic rectal resection (LRR) vs open rectal resection (ORR) to evaluate the pathologic outcomes of surgery in light of the most recent evidence on the topic. We investigated whether any differences are found in terms of CRM involvement (≤1 mm) and achievement of a complete mesorectal excision between LRR and ORR for rectal cancer.

Methods
Study Design and Inclusion Criteria

This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statements checklist.22 The eligibility and selection criteria were defined before initiating the data search to ensure the proper identification of all eligible studies. Only RCTs on rectal cancer that compared LRR and ORR and reported at least 1 of the outcomes of interest were retrieved and analyzed. No trial duration limitation was applied. Prospective nonrandomized studies, retrospective studies, case reports, reviews, commentaries, and conference abstracts were not considered. Moreover, articles reporting the results of surgical teams during their learning curve for LRR were also discarded. The study methods and analyses were reviewed to ensure the respect of the ethical principles for biomedical research.

By applying the PICO (Problem/Population, Intervention, Comparison, and Outcome) framework, we defined study selection criteria. Participants included adult patients with histologically proven rectal cancer requiring surgical resection. Interventions consisted of LRR (including laparoscopic-assisted) and ORR (ie, TME or partial mesorectal excision). Studies were included independently of the surgical technique (eg, abdominoperineal resection or anterior resection) and the performance of a primary anastomosis. In all included studies, LRR was compared with ORR. Primary outcome measures consisted of the rate of positive CRM (defined as ≤1 mm from the closest tumor to the cut edge of the tissue) and the rate of complete mesorectal excision, as classified by Nagtegaal et al23 (ie, achievement of intact mesorectum with only minor irregularities of a smooth mesorectal surface with no defects deeper than 5 mm and no coning toward the distal margin of the specimen). The secondary outcomes included the distance of the free radial margin (in millimeters), the rate of positive distal margins, the distance to the distal margin (in centimeters), and the total number of lymph nodes retrieved.

Literature Search Strategy

A literature search was performed of the Cochrane Central Register of Controlled Trials, MEDLINE (through PubMed), EMBASE, and Scopus databases. Specific research equations were formulated for each database using the following keywords and/or MeSH terms: rectal/colorectal cancer/carcinoma, treatment, therapy, management, surgery, laparoscopy/laparoscopic surgery, open surgery/laparotomy, and randomized trial/trial. Moreover, the reference lists of the eligible studies and relevant review articles were cross-checked to identify additional pertinent studies. The clinicaltrials.gov registry was also searched to look for any possible ongoing RCT for which results might be published in the near future. We retrieved articles published in English from January 1, 1995, to June 30, 2016, that met the selection criteria.

Study Selection and Quality Assessment

The title and abstract of the retrieved studies were independently and blindly screened for relevance according to the CONSORT Statement 2010 for RCTs (http://www.consort-statement.org) by 2 reviewers (A.M.-P. and N.de’A.). To enhance sensitivity, records were removed only if both reviewers excluded the record at the title and abstract screening level. Subsequently, both reviewers performed a full-text analysis of the selected articles. Both reviewers independently assessed the risk for bias using the Cochrane tool for assessing risk for bias, as described in the Cochrane Handbook for Systematic Reviews of Interventions.24 In addition, the Grading of Recommendations Assessment Development and Evaluation (GRADE) system was used to grade the body of evidence emerging from this study.25 All disagreements between the 2 reviewers in the selection and evaluation processes were resolved by discussion with a third reviewer (F.B.).

Data Extraction and Analysis

Data from the included studies were processed for the qualitative and quantitative analyses. For binary outcome data, the risk ratio (RR) and 95% CIs were estimated using the Mantel-Haenszel method; a RR of less than 1.00 favored laparoscopy. For continuous data, the mean differences and 95% CIs were estimated using inverse variance weighting. Outcome measures (mean [SD] and median [interquartile range] values) were extracted for each surgical treatment. If necessary and possible, outcome variables were calculated based on the data available in the individual selected studies. If the SE was provided instead of the SD, the SD was calculated based on the sample size (SE = SD/√N). The 95% CI was then calculated as SE × 1.96 (upper boundary) and SE × −1.96 (lower boundary). In studies in which the mean or SD was not reported, these values were estimated from the median, range (interquartile range), or P value.26,27 Heterogeneity was assessed by the I2 statistic,24,28,29 and values of 25%, 50%, and 75% were considered low, moderate, and high, respectively.24,29 The pooled estimates of the mean differences were calculated using random-effects models to take into account potential interstudy heterogeneity and to adopt a more conservative approach. Then, the robustness of the results and the potential sources of heterogeneity were explored by performing sensitivity analyses. The pooled effect was considered significant if P < .05. The meta-analysis was performed using RevMan software (version 5.3; Cochrane Collaboration).

Results
Literature Search and Selection

Overall, the combined search identified 6205 articles, of which 5836 were rejected based on the title and abstract evaluation. The remaining 369 articles underwent full-text evaluation, and 355 were excluded. No additional study was identified through manual search, cross-check of reference lists, or search of clinicaltrials.gov. Fourteen unique RCTs were found eligible and were evaluated for the qualitative and quantitative analyses. The PRISMA diagram of the literature search and the study selection process is shown in Figure 1.

Study Characteristics

The 14 selected studies were published from May 2003 through October 2015. They included patients who underwent surgery from September 1993 through November 2014. Overall, these studies analyzed a total of 4034 unique patients undergoing LRR or ORR (Table). The LRR group included 2265 patients with a mean (SD) age of 63.3 (4.6) years, and 1272 (56.2%) were male; 293 of 2230 patients (13.1%) required conversion from an LRR to ORR. The ORR group included 1769 patients with a mean (SD) age of 62.5 (3.9) years, and 1033 (58.4%) were male.

Primary Outcomes

Nine studies reported the rate of CRM involvement by considering CRM as positive when 1 mm or less.13-15,20,21,30,33-35 Data from Braga et al37 were not included in the meta-analysis owing to the lack of a precise definition of CRM involvement. The pooled data from the RCTs found positive CRM in 135 (7.9%) of 1697 patients who underwent LRR and in 79 (6.1%) of 1292 patients who underwent ORR; the RR was 1.17 (95% CI, 0.89-1.53; P = .26) with no heterogeneity (I2 = 0%) (Figure 2A).

Five studies13,14,20,21,30 reported the rate of complete mesorectal excision. A noncomplete mesorectal excision (nearly complete or incomplete) was observed in 179 (13.2%) of 1354 patients who underwent LRR and in 104 (10.4%) of 998 patients who underwent ORR; the RR was 1.31 (95% CI, 1.05-1.64; P = .02) with no heterogeneity (I2 = 0%) (Figure 2B). The sensitivity analysis showed no difference between random- and fixed-effects models. Moreover, confirmatory results were observed when performing a subgroup analysis by including only the 4 major multicentric RCTs.13,14,20,21

Secondary Outcomes

The rate of positive distal margins was reported in 4 studies only.20,21,34,37 Two of these studies reported no involvement in the LRR and ORR groups.34,37 Positivity of distal margins was reported in 6 (0.9%) of 662 patients who underwent LRR and in 5 (0.8%) of 645 patients who underwent ORR (P = .86) (Figure 3A). Similarly, no significant difference was observed between LRR and ORR for the distance to the distal margin,13,14,20,21 the distance to the radial margin,13,14,20,21,31,32 or the number of lymph nodes harvested13,14,20,30-38 (Figure 3B-D). The distal resection margin involvement (RR, 1.12; 95% CI, 0.34-3.67; P = .86) was not different between LRR and ORR (Figure 3A). Similarly, the mean difference in the distance to the radial margin was −0.67 mm (95% CI, −2.16 to 0.83 mm; P = .38; heterogeneity, I2 = 74%) (Figure 3B); the mean difference in the distance to the distal margin was 0.01 cm (95% CI, −0.12 to 0.15 cm; P = .87; heterogeneity, I2 = 36%) (Figure 3C); and the mean difference in the number of lymph nodes harvested was 0.05 (95% CI, −0.77 to 0.86; P = .91; heterogeneity, I2 = 60%) (Figure 3D) without significant differences between LRR and ORR.The sensitivity analyses performed confirmed the results of the main analysis.

Study Quality Assessment

The assessment of study quality and the risk for bias is shown in the eFigure in the Supplement. Overall, 10 studies were classified at a low risk,13-15,20,21,30,33-35,37 1 at an unknown risk,31 and 3 at a high risk for bias.32,36,38 By applying the GRADE system, the quality of the evidence was rated as high for 10 studies13-15,20,21,30,33-35,37 and as moderate for the remaining 4 studies.31,32,36,38

Discussion

The present systematic review and meta-analysis focusing on the pathologic outcomes of laparoscopic resections for rectal cancer demonstrates that the rate of noncomplete mesorectal excision is significantly higher in patients undergoing LRR than for patients undergoing ORR. Moreover, no benefit compared with open surgery has been observed in terms of CRM involvement rates and all other pathologic variables investigated after LRR.

The completeness of the mesorectal resection is a valuable item to assess the oncologic safety of rectal surgery and a predictor of tumor recurrence in the pelvis.6,10,39 Indeed, the violation of the peritonealized posterior surface of the mesorectum was an important risk factor for local recurrence in patients with negative CRM. As can be observed in this meta-analysis, pooled data from the included RCTs showed a significantly higher rate of complete mesorectal excision in ORR (894 of 998 [89.6%]) compared with LRR (1175 of 1354 [86.8%]). These findings are based on 5 studies,13,14,20,21,30 among which the 4 most recent and largest multicentric RCTs specifically focused on the surgical and pathologic outcomes of LRR (ie, the COLOR II [Colorectal Cancer Laparoscopic or Open Resection II],13 COREAN [Comparison of Open vs Laparoscopic Surgery for Mid and Low Rectal Cancer After Neoadjuvant Chemoradiotherapy],14 ALACART [Australasian Laparoscopic Cancer of the Rectum],21 and ACOSOG Z6051 [Laparoscopic-Assisted Resection or Open Resection in Treating Patients With Rectal Cancer]20 studies). Conversely, the rate of positive CRM (defined as ≤1 mm) was found to be similar between LRR and ORR based on 9 RCTs.13-15,20,21,30,33-35 Among these studies, only the COLOR II and COREAN trials show a slight, although statistically nonsignificant, benefit in terms of CRM involvement for the laparoscopic approach. However, the COLOR II trial,13 which reported rates of CRM involvement of 7.3% in the LRR group and 8.7% in the ORR group, had a remarkably high proportion of missing CRM data (12% in the laparoscopic group and 8% in the open group). The COREAN study14 showed a lower rate of positive CRM in patients undergoing LRR (2.9%) compared with ORR (4.1%), but this trial included only patients who received preoperative chemoradiotherapy; a careful reading of the article discloses that major pathologic responses (grades 3 and 4)40 and the rate of T0 to T1 findings in the final pathologic report were higher in the LRR group than in the ORR group (43.7% vs 27.0% and 31.7% vs 18.2%, respectively). Thus, the LRR group included more patients with better responses to neoadjuvant therapies and less viable tumors, which can drastically affect CRM involvement.41

Achieving negative CRM is challenging in clinical practice, with a rate of CRM positivity reaching 15% of TME despite optimal cylindrical or extralevator resections42,43; achieving this might be even harder with laparoscopy. However, the cutoff value for defining positive CRM is still under debate, with the threshold of 1 mm or less as the most frequently used in the literature. Nevertheless, some investigators proposed 2 mm or less rather than 1 mm or less to define a positive CRM—a potential source of confusion and heterogeneity in the literature.44,45

The 2 most recent multicenter RCTs that specifically focused on the pathologic outcomes of surgery20,21 used a composite variable, including complete mesorectal excision23 and negative radial and distal margins (both >1 mm) to assess the oncologic efficacy of LRR and ORR. The proposed composite outcome represents a stricter and more precise variable to assess the pathologic adequacy of the surgical resection compared with the CRM or TME quality taken separately, although the validity and usefulness of the composite outcome as a prognostic factor must be confirmed with the long-term results. The ACOSOG Z6501 and ALACART trials had a noninferiority design for the LRR vs ORR approaches and reached the same conclusion. Compared with open surgery, the noninferiority of laparoscopic surgery for successful resection was not established; thus, the authors did not support the routine use of laparoscopy in patients with rectal cancer.20,21 The present meta-analysis is in accordance with these recent findings and in contrast with previous ones.17-19 Indeed, a meta-analysis based on 8 RCTs and 19 prospective and retrospective studies published in 201519 showed no differences in terms of oncologic safety between the LRR and ORR approaches, but as previously mentioned, the 3 most recent RCTs published20,21,30 were not included. What remains to be assessed are the outcomes of surgery according to the tumor location (eg, low, middle, and high rectal cancer), tumor stage, and type of surgical procedure (eg, low anterior resection, abdominoperineal resection). Based on the available literature, we could not ascertain reliable data about the effect of these factors on the pathologic outcomes of the surgical approach. However, reading future studies focused on particular subsets of tumor or surgical settings would be of interest to explore all applications of laparoscopy in the broad spectrum of rectal cancers.

In the past, the improvement of pelvic visualization provided by laparoscopy was expected to result in better pathologic outcomes. However, as can be observed in the present meta-analysis, the rate of complete mesorectal excision for LRR was lower than that for ORR. A possible explanation would be that conventional laparoscopic instruments can be highly challenging to use and jeopardize the achievement of the best plane of dissection for complete mesorectal removal, especially in the narrow or irradiated pelvis. From this perspective, mesorectal excision might be one of the interventions in which robotic methods could have an important role in contemporary digestive surgery.46-49 The remote control, along with the placement of wristed instruments in line with pelvic walls, allows the surgeon to perform the rectal resection much more ergonomically. A recent systematic review including 1776 patients who underwent robotic surgery for rectal cancer50 showed a rate of CRM positivity ranging from 0% to 7.5%. However, evidence is lacking; only a small-sized RCT has been published comparing the outcomes of robotic vs laparoscopic surgery, and that RCT shows a significantly shorter length of hospital stay in the robotic group.51 The results of the ROLARR (Robotic vs Laparoscopic Resection for Rectal Cancer) trial,52 awaited in the near future, will probably help to elucidate the role of robotic surgery for rectal cancer treatment.

Alternatively, rectal cancer can be approached by transanal TME.53 The COLOR III study54 was designed to compare transanal TME and laparoscopic TME for middle and low rectal cancers. This trial is just at the recruitment phase, although the investigators expect that transanal TME would be superior to laparoscopic TME in terms of oncologic outcomes.54

Limitations

The present meta-analysis relies solely on RCTs; this type of study is considered to provide the best level of evidence. However, potential bias cannot be completely ruled out. For instance, the protocols of neoadjuvant chemoradiotherapy were not standardized among all of the included studies; various surgical procedures (eg, anterior resections, abdominoperineal amputations, hand-assisted minimally invasive surgery) were performed in different proportions in the included RCTs; missing data about positive distal margins and missing definitions of resection margin involvement were observed.20,21 Despite these limitations, the robustness and consistency of the results were supported by the sensitivity analyses and the low heterogeneity observed. Moreover, the overall level of evidence emerging from the literature was judged as high.

Conclusions

Based on the available data pooled from the most recent RCTs, the complete mesorectal excision rate is significantly higher in patients undergoing ORR than LRR for rectal cancer. No differences between the 2 surgical approaches were observed for CRM involvement and the other pathologic outcomes. These findings dampen enthusiasm in support of laparoscopy as an oncologically safe approach for the treatment of rectal cancer. However, the long-term results of the ongoing RCTs are awaited to provide a definitive response to the question of whether these results have an influence on disease-free and overall patient survival.

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Article Information

Corresponding Author: Nicola de’Angelis, MD, PhD, Department of Digestive, Hepatobiliary Surgery and Liver Transplantation, Henri Mondor University Hospital, Assistance Publique–Hôpitaux de Paris, Université Paris Est–Créteil, 51 Avenue du Maréchal de Lattre de Tassigny, 94010 Créteil, France (nic.deangelis@yahoo.it).

Accepted for Publication: November 24, 2016.

Published Online: February 8, 2017. doi:10.1001/jamasurg.2016.5665

Author Contributions: Dr Martínez-Pérez had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: All authors.

Acquisition, analysis, or interpretation of data: Martínez-Pérez, de’Angelis.

Drafting of the manuscript: Martínez-Pérez, Carra, Brunetti.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Martínez-Pérez, Carra, de’Angelis.

Administrative, technical, or material support: de’Angelis.

Study supervision: Brunetti, de’Angelis.

Conflict of Interest Disclosures: None reported.

References
1.
Siegel  R, Ma  J, Zou  Z, Jemal  A.  Cancer statistics, 2014.  CA Cancer J Clin. 2014;64(1):9-29.PubMedGoogle ScholarCrossref
2.
Ferlay  J, Soerjomataram  I, Dikshit  R,  et al.  Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012.  Int J Cancer. 2015;136(5):E359-E386.PubMedGoogle ScholarCrossref
3.
Ferlay  J, Steliarova-Foucher  E, Lortet-Tieulent  J,  et al.  Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012.  Eur J Cancer. 2013;49(6):1374-1403.PubMedGoogle ScholarCrossref
4.
American Cancer Society. Cancer facts and figures 2014. Atlanta, GA: American Cancer Society; 2014. http://www.cancer.org/acs/groups/content/@research/documents/webcontent/acspc-042151.pdf. Accessed July 2016.
5.
De Caluwé  L, Van Nieuwenhove  Y, Ceelen  WP.  Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer.  Cochrane Database Syst Rev. 2013;(2):CD006041.PubMedGoogle Scholar
6.
Quirke  P, Steele  R, Monson  J,  et al; MRC CR07/NCIC-CTG CO16 Trial Investigators; NCRI Colorectal Cancer Study Group.  Effect of the plane of surgery achieved on local recurrence in patients with operable rectal cancer: a prospective study using data from the MRC CR07 and NCIC-CTG CO16 randomised clinical trial.  Lancet. 2009;373(9666):821-828.PubMedGoogle ScholarCrossref
7.
Kusters  M, Marijnen  CA, van de Velde  CJ,  et al.  Patterns of local recurrence in rectal cancer; a study of the Dutch TME trial.  Eur J Surg Oncol. 2010;36(5):470-476.PubMedGoogle ScholarCrossref
8.
Nagtegaal  ID, Quirke  P.  What is the role for the circumferential margin in the modern treatment of rectal cancer?  J Clin Oncol. 2008;26(2):303-312.PubMedGoogle ScholarCrossref
9.
Birbeck  KF, Macklin  CP, Tiffin  NJ,  et al.  Rates of circumferential resection margin involvement vary between surgeons and predict outcomes in rectal cancer surgery.  Ann Surg. 2002;235(4):449-457.PubMedGoogle ScholarCrossref
10.
García-Granero  E, Faiz  O, Muñoz  E,  et al.  Macroscopic assessment of mesorectal excision in rectal cancer: a useful tool for improving quality control in a multidisciplinary team.  Cancer. 2009;115(15):3400-3411.PubMedGoogle ScholarCrossref
11.
Trakarnsanga  A, Gonen  M, Shia  J,  et al.  What is the significance of the circumferential margin in locally advanced rectal cancer after neoadjuvant chemoradiotherapy?  Ann Surg Oncol. 2013;20(4):1179-1184.PubMedGoogle ScholarCrossref
12.
Augestad  KM, Lindsetmo  RO, Reynolds  H,  et al.  International trends in surgical treatment of rectal cancer.  Am J Surg. 2011;201(3):353-357.PubMedGoogle ScholarCrossref
13.
van der Pas  MH, Haglind  E, Cuesta  MA,  et al; COlorectal cancer Laparoscopic or Open Resection II (COLOR II) Study Group.  Laparoscopic versus open surgery for rectal cancer (COLOR II): short-term outcomes of a randomised, phase 3 trial.  Lancet Oncol. 2013;14(3):210-218.PubMedGoogle ScholarCrossref
14.
Kang  SB, Park  JW, Jeong  SY,  et al.  Open versus laparoscopic surgery for mid or low rectal cancer after neoadjuvant chemoradiotherapy (COREAN trial): short-term outcomes of an open-label randomised controlled trial.  Lancet Oncol. 2010;11(7):637-645.PubMedGoogle ScholarCrossref
15.
Guillou  PJ, Quirke  P, Thorpe  H,  et al; MRC CLASICC Trial Group.  Short-term endpoints of conventional versus laparoscopic-assisted surgery in patients with colorectal cancer (MRC CLASICC trial): multicentre, randomised controlled trial.  Lancet. 2005;365(9472):1718-1726.PubMedGoogle ScholarCrossref
16.
Zhao  JK, Chen  NZ, Zheng  JB, He  S, Sun  XJ.  Laparoscopic versus open surgery for rectal cancer: Results of a systematic review and meta-analysis on clinical efficacy.  Mol Clin Oncol. 2014;2(6):1097-1102.PubMedGoogle Scholar
17.
Vennix  S, Pelzers  L, Bouvy  N,  et al.  Laparoscopic versus open total mesorectal excision for rectal cancer.  Cochrane Database Syst Rev. 2014;(4):CD005200.PubMedGoogle Scholar
18.
Xiong  B, Ma  L, Zhang  C.  Laparoscopic versus open total mesorectal excision for middle and low rectal cancer: a meta-analysis of results of randomized controlled trials.  J Laparoendosc Adv Surg Tech A. 2012;22(7):674-684.PubMedGoogle ScholarCrossref
19.
Arezzo  A, Passera  R, Salvai  A,  et al.  Laparoscopy for rectal cancer is oncologically adequate: a systematic review and meta-analysis of the literature.  Surg Endosc. 2015;29(2):334-348.PubMedGoogle ScholarCrossref
20.
Fleshman  J, Branda  M, Sargent  DJ,  et al.  Effect of laparoscopic-assisted resection vs open resection of stage II or III rectal cancer on pathologic outcomes: the ACOSOG Z6051 randomized clinical trial.  JAMA. 2015;314(13):1346-1355.PubMedGoogle ScholarCrossref
21.
Stevenson  AR, Solomon  MJ, Lumley  JW,  et al; ALaCaRT Investigators.  Effect of laparoscopic-assisted resection vs open resection on pathological outcomes in rectal cancer: the ALaCaRT randomized clinical trial.  JAMA. 2015;314(13):1356-1363.PubMedGoogle ScholarCrossref
22.
Moher  D, Liberati  A, Tetzlaff  J, Altman  DG, Group  P; PRISMA Group.  Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.  Int J Surg. 2010;8(5):336-341.PubMedGoogle ScholarCrossref
23.
Nagtegaal  ID, van de Velde  CJ, van der Worp  E, Kapiteijn  E, Quirke  P, van Krieken  JH; Cooperative Clinical Investigators of the Dutch Colorectal Cancer Group.  Macroscopic evaluation of rectal cancer resection specimen: clinical significance of the pathologist in quality control.  J Clin Oncol. 2002;20(7):1729-1734.PubMedGoogle ScholarCrossref
24.
Higgins  JP, Altman  DG, Gøtzsche  PC,  et al; Cochrane Bias Methods Group; Cochrane Statistical Methods Group.  The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials.  BMJ. 2011;343:d5928.PubMedGoogle ScholarCrossref
25.
Guyatt  GH, Oxman  AD, Vist  GE,  et al; GRADE Working Group.  GRADE: an emerging consensus on rating quality of evidence and strength of recommendations.  BMJ. 2008;336(7650):924-926.PubMedGoogle ScholarCrossref
26.
Hozo  SP, Djulbegovic  B, Hozo  I.  Estimating the mean and variance from the median, range, and the size of a sample.  BMC Med Res Methodol. 2005;5:13.PubMedGoogle ScholarCrossref
27.
Higgins  JP, Green  S, eds. The Cochrane Handbook for Systematic Reviews of Interventions, Version 5.1.0. http://handbook.cochrane.org. Updated March 2011. Accessed January 7, 2017.
28.
Harbour  R, Miller  J.  A new system for grading recommendations in evidence based guidelines.  BMJ. 2001;323(7308):334-336.PubMedGoogle ScholarCrossref
29.
Higgins  JP, Thompson  SG, Deeks  JJ, Altman  DG.  Measuring inconsistency in meta-analyses.  BMJ. 2003;327(7414):557-560.PubMedGoogle ScholarCrossref
30.
Ng  SS, Lee  JF, Yiu  RY,  et al.  Laparoscopic-assisted versus open total mesorectal excision with anal sphincter preservation for mid and low rectal cancer: a prospective, randomized trial.  Surg Endosc. 2014;28(1):297-306.PubMedGoogle ScholarCrossref
31.
Liang  X, Hou  S, Liu  H,  et al.  Effectiveness and safety of laparoscopic resection versus open surgery in patients with rectal cancer: a randomized, controlled trial from China.  J Laparoendosc Adv Surg Tech A. 2011;21(5):381-385.PubMedGoogle ScholarCrossref
32.
Liu  FL, Lin  JJ, Ye  F, Teng  LS.  Hand-assisted laparoscopic surgery versus the open approach in curative resection of rectal cancer.  J Int Med Res. 2010;38(3):916-922.PubMedGoogle ScholarCrossref
33.
Ng  SS, Leung  KL, Lee  JF, Yiu  RY, Li  JC, Hon  SS.  Long-term morbidity and oncologic outcomes of laparoscopic-assisted anterior resection for upper rectal cancer: ten-year results of a prospective, randomized trial.  Dis Colon Rectum. 2009;52(4):558-566.PubMedGoogle ScholarCrossref
34.
Luján  J, Valero  G, Hernandez  Q, Sanchez  A, Frutos  MD, Parrilla  P.  Randomized clinical trial comparing laparoscopic and open surgery in patients with rectal cancer.  Br J Surg. 2009;96(9):982-989.PubMedGoogle ScholarCrossref
35.
Ng  SS, Leung  KL, Lee  JF,  et al.  Laparoscopic-assisted versus open abdominoperineal resection for low rectal cancer: a prospective randomized trial.  Ann Surg Oncol. 2008;15(9):2418-2425.PubMedGoogle ScholarCrossref
36.
Pechlivanides  G, Gouvas  N, Tsiaoussis  J,  et al.  Lymph node clearance after total mesorectal excision for rectal cancer: laparoscopic versus open approach.  Dig Dis. 2007;25(1):94-99.PubMedGoogle ScholarCrossref
37.
Braga  M, Frasson  M, Vignali  A, Zuliani  W, Capretti  G, Di Carlo  V.  Laparoscopic resection in rectal cancer patients: outcome and cost-benefit analysis.  Dis Colon Rectum. 2007;50(4):464-471.PubMedGoogle ScholarCrossref
38.
Araujo  SE, da Silva eSousa  AH  Jr, de Campos  FG,  et al.  Conventional approach x laparoscopic abdominoperineal resection for rectal cancer treatment after neoadjuvant chemoradiation: results of a prospective randomized trial.  Rev Hosp Clin Fac Med Sao Paulo. 2003;58(3):133-140.PubMedGoogle Scholar
39.
Parfitt  JR, Driman  DK.  The total mesorectal excision specimen for rectal cancer: a review of its pathological assessment.  J Clin Pathol. 2007;60(8):849-855.PubMedGoogle ScholarCrossref
40.
Dworak  O, Keilholz  L, Hoffmann  A.  Pathological features of rectal cancer after preoperative radiochemotherapy.  Int J Colorectal Dis. 1997;12(1):19-23.PubMedGoogle ScholarCrossref
41.
Al-Sukhni  E, Attwood  K, Gabriel  E, Nurkin  SJ.  Predictors of circumferential resection margin involvement in surgically resected rectal cancer: a retrospective review of 23,464 patients in the US National Cancer Database.  Int J Surg. 2016;28:112-117.PubMedGoogle ScholarCrossref
42.
Martijnse  IS, Dudink  RL, West  NP,  et al.  Focus on extralevator perineal dissection in supine position for low rectal cancer has led to better quality of surgery and oncologic outcome.  Ann Surg Oncol. 2012;19(3):786-793.PubMedGoogle ScholarCrossref
43.
West  NP, Finan  PJ, Anderin  C, Lindholm  J, Holm  T, Quirke  P.  Evidence of the oncologic superiority of cylindrical abdominoperineal excision for low rectal cancer.  J Clin Oncol. 2008;26(21):3517-3522.PubMedGoogle ScholarCrossref
44.
Nagtegaal  ID, Marijnen  CA, Kranenbarg  EK, van de Velde  CJ, van Krieken  JH; Pathology Review Committee; Cooperative Clinical Investigators.  Circumferential margin involvement is still an important predictor of local recurrence in rectal carcinoma: not one millimeter but two millimeters is the limit.  Am J Surg Pathol. 2002;26(3):350-357.PubMedGoogle ScholarCrossref
45.
Tilney  HS, Rasheed  S, Northover  JM, Tekkis  PP.  The influence of circumferential resection margins on long-term outcomes following rectal cancer surgery.  Dis Colon Rectum. 2009;52(10):1723-1729.PubMedGoogle ScholarCrossref
46.
de’Angelis  N, Lizzi  V, Azoulay  D, Brunetti  F.  Robotic vs laparoscopic right colectomy for colon cancer: analysis of the initial simultaneous learning curve of a surgical fellow.  J Laparoendosc Adv Surg Tech A. 2016;26(11):882-892.PubMedGoogle ScholarCrossref
47.
Ahmed  J, Nasir  M, Flashman  K, Khan  J, Parvaiz  A.  Totally robotic rectal resection: an experience of the first 100 consecutive cases.  Int J Colorectal Dis. 2016;31(4):869-876.PubMedGoogle ScholarCrossref
48.
de’Angelis  N, Portigliotti  L, Azoulay  D, Brunetti  F.  Robotic surgery: a step forward in the wide spread of minimally invasive colorectal surgery.  J Minim Access Surg. 2015;11(4):285-286.PubMedGoogle ScholarCrossref
49.
de’Angelis  N, Portigliotti  L, Brunetti  F.  Robot-assisted rectal cancer surgery deserves a fair trial.  Colorectal Dis. 2015;17(9):824-825.PubMedGoogle ScholarCrossref
50.
Araujo  SE, Seid  VE, Klajner  S.  Robotic surgery for rectal cancer: current immediate clinical and oncological outcomes.  World J Gastroenterol. 2014;20(39):14359-14370.PubMedGoogle ScholarCrossref
51.
Baik  SH, Ko  YT, Kang  CM,  et al.  Robotic tumor-specific mesorectal excision of rectal cancer: short-term outcome of a pilot randomized trial.  Surg Endosc. 2008;22(7):1601-1608.PubMedGoogle ScholarCrossref
52.
Collinson  FJ, Jayne  DG, Pigazzi  A,  et al.  An international, multicentre, prospective, randomised, controlled, unblinded, parallel-group trial of robotic-assisted versus standard laparoscopic surgery for the curative treatment of rectal cancer.  Int J Colorectal Dis. 2012;27(2):233-241.PubMedGoogle ScholarCrossref
53.
de’Angelis  N, Portigliotti  L, Azoulay  D, Brunetti  F.  Transanal total mesorectal excision for rectal cancer: a single center experience and systematic review of the literature.  Langenbecks Arch Surg. 2015;400(8):945-959.PubMedGoogle ScholarCrossref
54.
Deijen  CL, Velthuis  S, Tsai  A,  et al.  COLOR III: a multicenter randomized clinical trial comparing transanal TME vs laparoscopic TME for mid and low rectal cancer.  Surg Endosc. 2016;30(8):3210-3215.PubMedGoogle ScholarCrossref
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