Fluorescence imaging by means of Indocyanine green (ICG) has been applied to intraoperatively determine the perfusion of the anastomosis. The purpose of this Individual Participant Database meta-analysis was to assess the effectiveness in decreasing the incidence of anastomotic leak (AL) after rectal cancer surgery.
We searched PubMed, Embase, Cochrane Library and ClinicalTrial.gov, EU Clinical Trials and ISRCTN registries on September 1st, 2019. We considered eligible those studies comparing the assessment of anastomotic perfusion during rectal cancer surgery by intraoperative use of ICG fluorescence compared with standard practice. We defined as primary outcome the incidence of AL at 30 days after surgery. The studies were assessed for quality by means of the ROBINS-I and the Cochrane risk tools. We calculated odds ratios (ORs) using the Individual patient data analysis, restricted to rectal lesions, according to original treatment allocation.
The review of the literature and international registries produced 15 published studies and 5 ongoing trials, for 9 of which the authors accepted to share individual participant data. 314 patients from two randomized trials, 452 from three prospective series and 564 from 4 non-randomized studies were included. Fluorescence imaging significantly reduced the incidence of AL (OR 0.341; 95% CI 0.220–0.530; p < 0.001), independent of age, gender, BMI, tumour and anastomotic distance from the anal verge and neoadjuvant therapy. Also, overall morbidity and reintervention rate were positively influenced by the use of ICG.
The incidence of AL may be reduced when ICG fluorescence imaging is used to assess the perfusion of a colorectal anastomosis. Limitations relate to the consistent number of non-randomized studies included and their heterogeneity in defining and assessing AL. Ongoing large randomized studies will help to determine the exact role of routine ICG fluorescence imaging may decrease the incidence of AL in surgery for rectal cancer.
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Vallance A, Wexner S, Berho M, Cahill R, Coleman M, Haboubi N, Heald RJ, Kennedy RH, Moran B, Mortensen N, Motson RW, Novell R, O'Connell PR, Ris F, Rockall T, Senapati A, Windsor A, Jayne DG (2017) A collaborative review of the current concepts and challenges of anastomotic leaks in colorectal surgery. Colorectal Dis 19:O1–O12
McDermott FD, Heeney A, Kelly ME, Steele RJ, Carlson GL, Winter DC (2015) Systematic review of preoperative, intraoperative and postoperative risk factors for colorectal anastomotic leaks. Br J Surg 102:462–479
Phitayakorn R, Delaney CP, Reynolds HL, Champagne BJ, Heriot AG, Neary P, Senagore AJ, International Anastomotic Leak Study G (2008) Standardized algorithms for management of anastomotic leaks and related abdominal and pelvic abscesses after colorectal surgery. World J Surg 32:1147–1156
T Pinkney group TESoCc (2017) The relationship between method of anastomosis and anastomotic failure after right hemicolectomy and ileo-caecal resection: an international snapshot audit. Colorectal Dis. https://doi.org/10.1111/codi.13646
Arezzo A, Migliore M, Chiaro P, Arolfo S, Filippini C, Di Cuonzo D, Cirocchi R, Morino M (2019) The REAL (REctal Anastomotic Leak) score for prediction of anastomotic leak after rectal cancer surgery. Tech Coloproctol 23:649–663
Tiernan J, Cook A, Geh I, George B, Magill L, Northover J, Verjee A, Wheeler J, Fearnhead N (2014) Use of a modified Delphi approach to develop research priorities for the association of coloproctology of Great Britain and Ireland. Colorectal Dis 16:965–970
Chadi SA, Fingerhut A, Berho M, DeMeester SR, Fleshman JW, Hyman NH, Margolin DA, Martz JE, McLemore EC, Molena D, Newman MI, Rafferty JF, Safar B, Senagore AJ, Zmora O, Wexner SD (2016) Emerging trends in the etiology, prevention, and treatment of gastrointestinal anastomotic leakage. J Gastrointest Surg 20:2035–2051
Rutegard M, Rutegard J (2015) Anastomotic leakage in rectal cancer surgery: the role of blood perfusion. World J Gastrointest Surg 7:289–292
Vignali A, Gianotti L, Braga M, Radaelli G, Malvezzi L, Di Carlo V (2000) Altered microperfusion at the rectal stump is predictive for rectal anastomotic leak. Dis Colon Rectum 43:76–82
Blanco-Colino R, Espin-Basany E (2018) Intraoperative use of ICG fluorescence imaging to reduce the risk of anastomotic leakage in colorectal surgery: a systematic review and meta-analysis. Tech Coloproctol 22:15–23
Stewart LA, Clarke M, Rovers M, Riley RD, Simmonds M, Stewart G, Tierney JF (2015) Preferred reporting items for systematic review and meta-analyses of individual participant data: the PRISMA-IPD statement. JAMA 313:1657–1665
Kim JC, Lee JL, Yoon YS, Alotaibi AM, Kim J (2016) Utility of indocyanine-green fluorescent imaging during robot-assisted sphincter-saving surgery on rectal cancer patients. Int J Med Robot 12:710–717
Martin-Perez B, Otero-Piñeiro A, DeLacy-Oliver B, Pena-Lopez R, Arroyave MC, Fernandez-Hevia M, Lacy A (2017) Transanal total mesorectal excision for rectal cancer: assessment with indocyanine green. Surg Endosc Other Intervent Techn 31:S204
Moore C, Turner J, Naddell C, Okonkwo A, Childs E, Clark C (2016) Short term outcomes in laparoscopic colorectal surgery with and without the use of fluorescent angiography. Surg Endosc Other Intervent Tech 30:S347
Quartey B, Chinn B, Wilkins K, Notaro J, Alva S, Saleem A, Rampakakis E, Starker P (2016) Real time intraoperative assessment of colonic perfusion in colon and rectal surgery. Dis Colon Rectum 59:e339–e340
Ramphal W, Crolla RMPH, Gobardhan PD, Wijsman JH, Van Der Schelling GP, Schreinemakers JMJ (2017) Colorectal perfusion with indocyanine green in colonic resection performed in robotic surgery: reducing the risk of anastomotic leakage? Surg Endosc Other Intervent Tech 31:S4
Mizrahi I, Abu-Gazala M, Rickles A, Fernandez L, Petrucci A, Wolf J, Sands D, Wexner SD (2017) Indocyanine green fluorescence angiography for low anterior resection: results of a comparative cohort study. Colorectal Dis 19:37
Sterne JA, Hernan MA, Reeves BC, Savovic J, Berkman ND, Viswanathan M, Henry D, Altman DG, Ansari MT, Boutron I, Carpenter JR, Chan AW, Churchill R, Deeks JJ, Hrobjartsson A, Kirkham J, Juni P, Loke YK, Pigott TD, Ramsay CR, Regidor D, Rothstein HR, Sandhu L, Santaguida PL, Schunemann HJ, Shea B, Shrier I, Tugwell P, Turner L, Valentine JC, Waddington H, Waters E, Wells GA, Whiting PF, Higgins JP (2016) ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ 355:i4919
Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, Savovic J, Schulz KF, Weeks L, Sterne JA (2011) The cochrane collaboration's tool for assessing risk of bias in randomised trials. BMJ 343:d5928
Foo (2016) The impact of indocyanine green-enhanced fluorescence imaging on bowel transection in left-sided colorectal resection. https://ClinicalTrials.gov/show/NCT02669485
Hospital OU, Oulu Uo, District CFH, Hospital TU, Hospital TU, Helsinki HDo, Uusimaa, Hospital PTC, Seinäjoki Central Hospital S, Finland (2018) Indocyanine green fluorescence imaging in prevention of colorectal anastomotic leakage. https://ClinicalTrials.gov/show/NCT03602677
University A, Hospital AAU (2015) The Role of Indocyanine Green (ICG) Fluorescence imaging on anastomotic leak in robotic colorectal surgery. https://ClinicalTrials.gov/show/NCT02598414
University Hospital G, Kanker KOT (2019) Assessment of graft perfusion and oxygenation for improved outcome in esophageal cancer surgery. https://ClinicalTrials.gov/show/NCT03587532
Zhang Z, Hospital PUMC, Hospital BCY, Institute C, Hospital CAoMS, Hospital CPG, Hospital PUPs, Hospital BC, Hospital B, Xinhua Hospital SJTUSoM, Hospital R, Hospital R, University F, Hospital GPPs, Southern Medical University C, University FHoCM, University FHoJ, University TFAHwNM, Hospital FMUU, University FAHoCM, Shanghai General Hospital SJTUSoM, Hospital BF (2019) Perfusion outcomes with near infrared-indocyanine green imaging system in laparoscopic total mesorectal excision for mid- or low-rectal cancer. https://ClinicalTrials.gov/show/NCT04012645
Armstrong G, Croft J, Corrigan N, Brown JM, Goh V, Quirke P, Hulme C, Tolan D, Kirby A, Cahill R, O'Connell PR, Miskovic D, Coleman M, Jayne D (2018) IntAct: intra-operative fluorescence angiography to prevent anastomotic leak in rectal cancer surgery: a randomized controlled trial. Colorectal Dis 20:O226–o234
Rybakow (2017) A study of perfusion of colorectal anastomosis using FLuorescence AnGiography (FLAG-trial). https://ClinicalTrials.gov/show/NCT03390517
Boni L, Fingerhut A, Marzorati A, Rausei S, Dionigi G, Cassinotti E (2017) Indocyanine green fluorescence angiography during laparoscopic low anterior resection: results of a case-matched study. Surg Endosc Other Intervent Tech 31:1836–1840
Ciarleglio FA, Brolese A, Marcucci S, Valduga P, Beltempo P, Prezzi C, Bondioli P, Berlanda G (2017) Preliminary results on application of da vinci fluorescence imaging vision system with indocyanine green (ICG) in robotic colo rectal surgery. Surg Endosc Other Intervent Tech 31:S470
Jafari MD, Lee KH, Halabi WJ, Mills SD, Carmichael JC, Stamos MJ, Pigazzi A (2013) The use of indocyanine green fluorescence to assess anastomotic perfusion during robotic assisted laparoscopic rectal surgery. Surg Endosc 27:3003–3008
Keller D, Ibarra S, Flores JR, Haas EM (2016) Impact of fluorescence angiography on clinical and financial outcomes in colorectal surgery: A case matched series. Gastroenterology 150:S1242
Kin C, Vo H, Welton L, Welton M (2015) Equivocal effect of intraoperative fluorescence angiography on colorectal anastomotic leaks. Dis Colon Rectum 58:582–587
Kudszus S, Roesel C, Schachtrupp A, Hoer JJ (2010) Intraoperative laser fluorescence angiography in colorectal surgery: a noninvasive analysis to reduce the rate of anastomotic leakage. Langenbeck's Archiv Surg 395:1025–1030
Ris F, Liot E, Buchs NC, Kraus R, Ismael G, Belfontali V, Douissard J, Cunningham C, Lindsey I, Guy R, Jones O, George B, Morel P, Mortensen NJ, Hompes R, Cahill RA (2018) Multicentre phase II trial of near-infrared imaging in elective colorectal surgery. Br J Surg 105:1359–1367
Watanabe J, Ishibe A, Suwa Y, Suwa H, Ota M, Kunisaki C, Endo I (2019) Indocyanine green fluorescence imaging to reduce the risk of anastomotic leakage in laparoscopic low anterior resection for rectal cancer: a propensity score-matched cohort study. Surg Endosc 34:202
De Nardi P, Elmore U, Maggi G, Maggiore R, Boni L, Cassinotti E, Fumagalli U, Gardani M, De Pascale S, Parise P, Vignali A, Rosati R (2019) Intraoperative angiography with indocyanine green to assess anastomosis perfusion in patients undergoing laparoscopic colorectal resection: results of a multicenter randomized controlled trial. Surg Endosc 34:53
Diana M, Agnus V, Halvax P, Liu YY, Dallemagne B, Schlagowski AI, Geny B, Diemunsch P, Lindner V, Marescaux J (2015) Intraoperative fluorescence-based enhanced reality laparoscopic real-time imaging to assess bowel perfusion at the anastomotic site in an experimental model. Br J Surg 102:e169–176
Dr Alessio Pigazzi received research support from Novadaq, Inc and is a consultant for Intuitive Surgical. Alberto Arezzo, Marco Augusto Bonino, Frédéric Ris, Luigi Boni, Elisa Cassinotti, Dominic Chi Chung Foo, Nga Fan Shum, Alberto Brolese, Francesco Ciarleglio, Deborah S Keller, Riccardo Rosati, Paola De Nardi, Ugo Elmore, Uberto Fumagalli, Mehraneh Dorna Jafari, Evgeny Rybakov, Mikhail Alekseev, Jun Watanabe, Nereo Vettoretto, Roberto Cirocchi, Roberto Passera, Mario Morino declare that they have no conflict of interest.
Ethical approval is not needed as this study corresponds to a meta-analysis of studies already published.
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Arezzo, A., Bonino, M.A., Ris, F. et al. Intraoperative use of fluorescence with indocyanine green reduces anastomotic leak rates in rectal cancer surgery: an individual participant data analysis. Surg Endosc (2020). https://doi.org/10.1007/s00464-020-07735-w
- Anastomotic leak
- Rectal surgery
- Indocyanine green
- Fluorescence imaging
- Rectal cancer