Effect of the Laparoscopic Approach in Reducing Postoperative Severe Complications Following Hepatectomy for Colorectal Liver Metastases

Postoperative Complications Clinical Trial

— METALAP  

Official title:

Effect of the Laparoscopic Approach in Reducing Postoperative Severe Complications Following Hepatectomy for Colorectal Liver Metastases: Prospective, Randomized, Controlled Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04163887
• Other study ID #: DIG-03-2019
• Status: Recruiting
• Phase: N/A
• Start date: January 27, 2021
• Est. completion date: January 27, 2026

Study information

• Verified date: February 2022
• Source: Institut Mutualiste Montsouris
• Contact: Caroline RIX
• Phone: +33 156616371
• Email: caroline.rix[@]imm.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objective of this study is to demonstrate the superiority of the laparoscopic approach over the open approach in the resection of colorectal liver metastases, by examining the reduction of postoperative complications (including mortality), measured using the Comprehensive Complication Index (CCI) within 90 days of the procedure or regardless of the date during the hospital stay.

Description:

While laparotomy is still the standard approach of resectable colorectal liver mestastases, its associated morbidity remains non-negligible with reported mortality and complications rates ranging from 2 to 8% and 30 to 70%, respectively (1). Besides the underlying liver disease together with the comorbidities of the patients, this high morbidity is also related to the type of surgical approach. Since less than 15% of liver resections are currently performed using the laparoscopic approach in France, a trial showing the superiority of the laparoscopic approach in comparison to the open approach for patients with colorectal liver metastases qualifying for both approaches would allow improving management of patients, reducing the length of stay, maybe decreasing the global cost and changing current practices on a national scale.

In order to demonstrate the superiority of the laparoscopic approach over the laparotomy approach, patients with colorectal hepatic metastasis will be randomly assigned to either the laparoscopy or laparotomy groups. Post-operative complications (including mortality) will be measured using the Comprehensive Complication Index (CCI) within 90 days postoperatively or at any time during hospitalization. The participation time for each patient in the study is 3 years, the patient will be followed at 1, 3, 6, 9, 9, 12, 15, 18, 21, 24, 30 and 36 months.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 340
• Est. completion date: January 27, 2026
• Est. primary completion date: April 27, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Presenting with colorectal liver metastases requiring liver resection ± concomitant radiofrequency ablation.

• Qualifying for both a laparoscopic approach and an open approach.

• Informed written consent.

• Affiliated to health insurance regimen.

Exclusion Criteria:

• Hybrid liver resection (including both laparoscopic and open resection).

• Liver resection requiring an associated vascular or biliary reconstruction.

• Contraindication to surgery.

• Contraindication to laparoscopy (pneumoperitoneum).

• ASA (American Society of Anesthesiologists) score IV or V or life expectancy < 3 months.

• Poor comprehension of French language or cognitive impairment

• Pregnancy or breastfeeding.

• Patient under guardianship or unable to give consent

• People particularly protected by French law.

Related Conditions & MeSH terms

• Liver Metastasis Colon Cancer
• Liver Neoplasms
• Neoplasm Metastasis
• Postoperative Complications

Intervention

Procedure:
• hepatectomy
Resection colorectal liver metastases using a laparoscopic approach or an open approach.

Locations

Country	Name	City	State
France	CHU Amiens Picardie	Amiens
France	Hôpital Côte de Nacre - Chu Caen	Caen
France	CHU Estaing	Clermont-Ferrand
France	Hôpital Beaujon	Clichy
France	CHU Henri Mondor	Créteil
France	CHU de Grenoble	Grenoble
France	Hôpital Claude Huriez	Lille
France	HCL - Hôpital Croix Rousse	Lyon
France	CHU de Marseille Hôpital de Timone	Marseille
France	l'Institut Paoli Calmettes	Marseille
France	CHU de Montpellier	Montpellier
France	CHU de Nancy - Hôpitaux Brabois	Nancy
France	Hôpital Cochin	Paris
France	Hôpital La pitié Salpêtrière	Paris
France	Institut Mutualiste Montsouris	Paris
France	CHU de Reims	Reims
France	Hôpital Charles Nicolle	Rouen
France	CHU de Strasbourg - Nouvel Hôpital Civil	Strasbourg
France	CHU Rangueil	Toulouse
France	Hôpital Trousseau	Tours
France	Hôpital Paul Brousse	Villejuif

Sponsors (3)

Lead Sponsor	Collaborator
Institut Mutualiste Montsouris	Ministry of Health, France, National Cancer Institute, France

Country where clinical trial is conducted

France, 

References & Publications (60)

Adam R, Pascal G, Azoulay D, Tanaka K, Castaing D, Bismuth H. Liver resection for colorectal metastases: the third hepatectomy. Ann Surg. 2003 Dec;238(6):871-83; discussion 883-4. — View Citation

Allard MA, Cunha AS, Gayet B, Adam R, Goere D, Bachellier P, Azoulay D, Ayav A, Navarro F, Pessaux P; Colorectal Liver Metastases-French Study Group. Early and Long-term Oncological Outcomes After Laparoscopic Resection for Colorectal Liver Metastases: A Propensity Score-based Analysis. Ann Surg. 2015 Nov;262(5):794-802. doi: 10.1097/SLA.0000000000001475. — View Citation

Balzan S, Belghiti J, Farges O, Ogata S, Sauvanet A, Delefosse D, Durand F. The "50-50 criteria" on postoperative day 5: an accurate predictor of liver failure and death after hepatectomy. Ann Surg. 2005 Dec;242(6):824-8, discussion 828-9. — View Citation

Beppu T, Wakabayashi G, Hasegawa K, Gotohda N, Mizuguchi T, Takahashi Y, Hirokawa F, Taniai N, Watanabe M, Katou M, Nagano H, Honda G, Baba H, Kokudo N, Konishi M, Hirata K, Yamamoto M, Uchiyama K, Uchida E, Kusachi S, Kubota K, Mori M, Takahashi K, Kikuchi K, Miyata H, Takahara T, Nakamura M, Kaneko H, Yamaue H, Miyazaki M, Takada T. Long-term and perioperative outcomes of laparoscopic versus open liver resection for colorectal liver metastases with propensity score matching: a multi-institutional Japanese study. J Hepatobiliary Pancreat Sci. 2015 Oct;22(10):711-20. doi: 10.1002/jhbp.261. Epub 2015 May 21. — View Citation

Blazeby JM, Fayers P, Conroy T, Sezer O, Ramage J, Rees M; European Organization for Research Treatment of Cancer (EORTC) Quality of Life Group. Validation of the European Organization for Research and Treatment of Cancer QLQ-LMC21 questionnaire for assessment of patient-reported outcomes during treatment of colorectal liver metastases. Br J Surg. 2009 Mar;96(3):291-8. doi: 10.1002/bjs.6471. — View Citation

Bonjer HJ, Deijen CL, Haglind E; COLOR II Study Group. A Randomized Trial of Laparoscopic versus Open Surgery for Rectal Cancer. N Engl J Med. 2015 Jul 9;373(2):194. doi: 10.1056/NEJMc1505367. — View Citation

Cannon RM, Scoggins CR, Callender GG, McMasters KM, Martin RC 2nd. Laparoscopic versus open resection of hepatic colorectal metastases. Surgery. 2012 Oct;152(4):567-73; discussion 573-4. doi: 10.1016/j.surg.2012.07.013. Epub 2012 Sep 1. — View Citation

Castaing D, Vibert E, Ricca L, Azoulay D, Adam R, Gayet B. Oncologic results of laparoscopic versus open hepatectomy for colorectal liver metastases in two specialized centers. Ann Surg. 2009 Nov;250(5):849-55. doi: 10.1097/SLA.0b013e3181bcaf63. — View Citation

Cauchy F, Fuks D, Nomi T, Schwarz L, Barbier L, Dokmak S, Scatton O, Belghiti J, Soubrane O, Gayet B. Risk factors and consequences of conversion in laparoscopic major liver resection. Br J Surg. 2015 Jun;102(7):785-95. doi: 10.1002/bjs.9806. Epub 2015 Apr 2. — View Citation

Cipriani F, Rawashdeh M, Stanton L, Armstrong T, Takhar A, Pearce NW, Primrose J, Abu Hilal M. Propensity score-based analysis of outcomes of laparoscopic versus open liver resection for colorectal metastases. Br J Surg. 2016 Oct;103(11):1504-12. doi: 10.1002/bjs.10211. Epub 2016 Aug 3. — View Citation

Ciria R, Cherqui D, Geller DA, Briceno J, Wakabayashi G. Comparative Short-term Benefits of Laparoscopic Liver Resection: 9000 Cases and Climbing. Ann Surg. 2016 Apr;263(4):761-77. doi: 10.1097/SLA.0000000000001413. Review. — View Citation

Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004 Aug;240(2):205-13. — View Citation

Elshamy M, Takahashi H, Akyuz M, Yazici P, Yigitbas H, Hammad AY, Aucejo FN, Quintini C, Fung J, Berber E. Evolution of a laparoscopic liver resection program: an analysis of 203 cases. Surg Endosc. 2017 Oct;31(10):4150-4155. doi: 10.1007/s00464-017-5468-2. Epub 2017 Mar 31. — View Citation

Farges O, Goutte N, Bendersky N, Falissard B; ACHBT-French Hepatectomy Study Group. Incidence and risks of liver resection: an all-inclusive French nationwide study. Ann Surg. 2012 Nov;256(5):697-704; discussion 704-5. doi: 10.1097/SLA.0b013e31827241d5. — View Citation

Fretland ÅA, Dagenborg VJ, Bjørnelv GMW, Kazaryan AM, Kristiansen R, Fagerland MW, Hausken J, Tønnessen TI, Abildgaard A, Barkhatov L, Yaqub S, Røsok BI, Bjørnbeth BA, Andersen MH, Flatmark K, Aas E, Edwin B. Laparoscopic Versus Open Resection for Colorectal Liver Metastases: The OSLO-COMET Randomized Controlled Trial. Ann Surg. 2018 Feb;267(2):199-207. doi: 10.1097/SLA.0000000000002353. — View Citation

Fretland AA, Sokolov A, Postriganova N, Kazaryan AM, Pischke SE, Nilsson PH, Rognes IN, Bjornbeth BA, Fagerland MW, Mollnes TE, Edwin B. Inflammatory Response After Laparoscopic Versus Open Resection of Colorectal Liver Metastases: Data From the Oslo-CoMet Trial. Medicine (Baltimore). 2015 Oct;94(42):e1786. doi: 10.1097/MD.0000000000001786. Erratum in: Medicine (Baltimore). 2016 Mar;95(10):e367e. — View Citation

Fuks D, Cauchy F, Ftériche S, Nomi T, Schwarz L, Dokmak S, Scatton O, Fusco G, Belghiti J, Gayet B, Soubrane O. Laparoscopy Decreases Pulmonary Complications in Patients Undergoing Major Liver Resection: A Propensity Score Analysis. Ann Surg. 2016 Feb;263(2):353-61. doi: 10.1097/SLA.0000000000001140. — View Citation

Gigot JF, Glineur D, Santiago Azagra J, Goergen M, Ceuterick M, Morino M, Etienne J, Marescaux J, Mutter D, van Krunckelsven L, Descottes B, Valleix D, Lachachi F, Bertrand C, Mansvelt B, Hubens G, Saey JP, Schockmel R; Hepatobiliary and Pancreatic Section of the Royal Belgian Society of Surgery and the Belgian Group for Endoscopic Surgery. Laparoscopic liver resection for malignant liver tumors: preliminary results of a multicenter European study. Ann Surg. 2002 Jul;236(1):90-7. — View Citation

Gilg S, Sparrelid E, Isaksson B, Lundell L, Nowak G, Strömberg C. Mortality-related risk factors and long-term survival after 4460 liver resections in Sweden-a population-based study. Langenbecks Arch Surg. 2017 Feb;402(1):105-113. doi: 10.1007/s00423-016-1512-2. Epub 2016 Oct 1. — View Citation

Graham JW, Olchowski AE, Gilreath TD. How many imputations are really needed? Some practical clarifications of multiple imputation theory. Prev Sci. 2007 Sep;8(3):206-13. Epub 2007 Jun 5. — View Citation

Hallet J, Sa Cunha A, Cherqui D, Gayet B, Goéré D, Bachellier P, Laurent A, Fuks D, Navarro F, Pessaux P; French Colorectal Liver Metastases Working Group, Association Française de Chirurgie. Laparoscopic Compared to Open Repeat Hepatectomy for Colorectal Liver Metastases: a Multi-institutional Propensity-Matched Analysis of Short- and Long-Term Outcomes. World J Surg. 2017 Dec;41(12):3189-3198. doi: 10.1007/s00268-017-4119-z. — View Citation

Hasegawa Y, Nitta H, Sasaki A, Takahara T, Itabashi H, Katagiri H, Otsuka K, Nishizuka S, Wakabayashi G. Long-term outcomes of laparoscopic versus open liver resection for liver metastases from colorectal cancer: A comparative analysis of 168 consecutive cases at a single center. Surgery. 2015 Jun;157(6):1065-72. doi: 10.1016/j.surg.2015.01.017. Epub 2015 Mar 16. — View Citation

Horan TC, Gaynes RP, Martone WJ, Jarvis WR, Emori TG. CDC definitions of nosocomial surgical site infections, 1992: a modification of CDC definitions of surgical wound infections. Am J Infect Control. 1992 Oct;20(5):271-4. — View Citation

Ishizawa T, Hasegawa K, Kokudo N, Sano K, Imamura H, Beck Y, Sugawara Y, Makuuchi M. Risk factors and management of ascites after liver resection to treat hepatocellular carcinoma. Arch Surg. 2009 Jan;144(1):46-51. doi: 10.1001/archsurg.2008.511. — View Citation

Karagkounis G, Akyuz M, Guerron AD, Yazici P, Aucejo FN, Quintini C, Miller CM, Vogt DP, Fung JJ, Berber E. Perioperative and oncologic outcomes of minimally invasive liver resection for colorectal metastases: A case-control study of 130 patients. Surgery. 2016 Oct;160(4):1097-1103. doi: 10.1016/j.surg.2016.04.043. Epub 2016 Jul 30. — View Citation

Karakousis GC, Singer S, Zheng J, Gonen M, Coit D, DeMatteo RP, Strong VE. Laparoscopic versus open gastric resections for primary gastrointestinal stromal tumors (GISTs): a size-matched comparison. Ann Surg Oncol. 2011 Jun;18(6):1599-605. doi: 10.1245/s10434-010-1517-y. Epub 2011 Jan 5. — View Citation

Kazaryan AM, Marangos IP, Røsok BI, Rosseland AR, Villanger O, Fosse E, Mathisen O, Edwin B. Laparoscopic resection of colorectal liver metastases: surgical and long-term oncologic outcome. Ann Surg. 2010 Dec;252(6):1005-12. doi: 10.1097/SLA.0b013e3181f66954. — View Citation

Koch M, Garden OJ, Padbury R, Rahbari NN, Adam R, Capussotti L, Fan ST, Yokoyama Y, Crawford M, Makuuchi M, Christophi C, Banting S, Brooke-Smith M, Usatoff V, Nagino M, Maddern G, Hugh TJ, Vauthey JN, Greig P, Rees M, Nimura Y, Figueras J, DeMatteo RP, Büchler MW, Weitz J. Bile leakage after hepatobiliary and pancreatic surgery: a definition and grading of severity by the International Study Group of Liver Surgery. Surgery. 2011 May;149(5):680-8. doi: 10.1016/j.surg.2010.12.002. Epub 2011 Feb 12. — View Citation

Komatsu S, Scatton O, Goumard C, Sepulveda A, Brustia R, Perdigao F, Soubrane O. Development Process and Technical Aspects of Laparoscopic Hepatectomy: Learning Curve Based on 15 Years of Experience. J Am Coll Surg. 2017 May;224(5):841-850. doi: 10.1016/j.jamcollsurg.2016.12.037. Epub 2017 Jan 20. — View Citation

Lawrence VA, Cornell JE, Smetana GW; American College of Physicians. Strategies to reduce postoperative pulmonary complications after noncardiothoracic surgery: systematic review for the American College of Physicians. Ann Intern Med. 2006 Apr 18;144(8):596-608. Review. — View Citation

Makabe K, Nitta H, Takahara T, Hasegawa Y, Kanno S, Nishizuka S, Sasaki A, Wakabayashi G. Efficacy of occlusion of hepatic artery and risk of carbon dioxide gas embolism during laparoscopic hepatectomy in a pig model. J Hepatobiliary Pancreat Sci. 2014 Aug;21(8):592-8. doi: 10.1002/jhbp.103. Epub 2014 Apr 21. — View Citation

Manfredi S, Lepage C, Hatem C, Coatmeur O, Faivre J, Bouvier AM. Epidemiology and management of liver metastases from colorectal cancer. Ann Surg. 2006 Aug;244(2):254-9. — View Citation

Martínez-Cecilia D, Cipriani F, Shelat V, Ratti F, Tranchart H, Barkhatov L, Tomassini F, Montalti R, Halls M, Troisi RI, Dagher I, Aldrighetti L, Edwin B, Abu Hilal M. Laparoscopic Versus Open Liver Resection for Colorectal Metastases in Elderly and Octogenarian Patients: A Multicenter Propensity Score Based Analysis of Short- and Long-term Outcomes. Ann Surg. 2017 Jun;265(6):1192-1200. doi: 10.1097/SLA.0000000000002147. — View Citation

Montalti R, Berardi G, Laurent S, Sebastiani S, Ferdinande L, Libbrecht LJ, Smeets P, Brescia A, Rogiers X, de Hemptinne B, Geboes K, Troisi RI. Laparoscopic liver resection compared to open approach in patients with colorectal liver metastases improves further resectability: Oncological outcomes of a case-control matched-pairs analysis. Eur J Surg Oncol. 2014 May;40(5):536-544. doi: 10.1016/j.ejso.2014.01.005. Epub 2014 Feb 2. — View Citation

Nachmany I, Pencovich N, Zohar N, Ben-Yehuda A, Binyamin C, Goykhman Y, Lubezky N, Nakache R, Klausner JM. Laparoscopic versus open liver resection for metastatic colorectal cancer. Eur J Surg Oncol. 2015 Dec;41(12):1615-20. doi: 10.1016/j.ejso.2015.09.014. Epub 2015 Sep 30. — View Citation

Nobili C, Marzano E, Oussoultzoglou E, Rosso E, Addeo P, Bachellier P, Jaeck D, Pessaux P. Multivariate analysis of risk factors for pulmonary complications after hepatic resection. Ann Surg. 2012 Mar;255(3):540-50. doi: 10.1097/SLA.0b013e3182485857. — View Citation

Nomi T, Fuks D, Ogiso S, Nakajima Y, Louvet C, Gayet B. Second and Third Laparoscopic Liver Resection for Patients With Recurrent Colorectal Liver Metastases. Ann Surg. 2016 May;263(5):e68-72. doi: 10.1097/SLA.0000000000001528. — View Citation

Okunrintemi V, Gani F, Pawlik TM. National Trends in Postoperative Outcomes and Cost Comparing Minimally Invasive Versus Open Liver and Pancreatic Surgery. J Gastrointest Surg. 2016 Nov;20(11):1836-1843. Epub 2016 Sep 9. — View Citation

Pham TH, Perry KA, Dolan JP, Schipper P, Sukumar M, Sheppard BC, Hunter JG. Comparison of perioperative outcomes after combined thoracoscopic-laparoscopic esophagectomy and open Ivor-Lewis esophagectomy. Am J Surg. 2010 May;199(5):594-8. doi: 10.1016/j.amjsurg.2010.01.005. — View Citation

Polignano FM, Quyn AJ, Sanjay P, Henderson NA, Tait IS. Totally laparoscopic strategies for the management of colorectal cancer with synchronous liver metastasis. Surg Endosc. 2012 Sep;26(9):2571-8. doi: 10.1007/s00464-012-2235-2. Epub 2012 Mar 22. — View Citation

Power DG, Kemeny NE. Role of adjuvant therapy after resection of colorectal cancer liver metastases. J Clin Oncol. 2010 May 1;28(13):2300-9. doi: 10.1200/JCO.2009.26.9340. Epub 2010 Apr 5. Review. — View Citation

Qiu J, Chen S, Pankaj P, Wu H. Laparoscopic hepatectomy is associated with considerably less morbidity and a long-term survival similar to that of the open procedure in patients with hepatic colorectal metastases. Surg Laparosc Endosc Percutan Tech. 2014 Dec;24(6):517-22. doi: 10.1097/SLE.0b013e31829cec2b. — View Citation

Rahbari NN, Garden OJ, Padbury R, Maddern G, Koch M, Hugh TJ, Fan ST, Nimura Y, Figueras J, Vauthey JN, Rees M, Adam R, Dematteo RP, Greig P, Usatoff V, Banting S, Nagino M, Capussotti L, Yokoyama Y, Brooke-Smith M, Crawford M, Christophi C, Makuuchi M, Büchler MW, Weitz J. Post-hepatectomy haemorrhage: a definition and grading by the International Study Group of Liver Surgery (ISGLS). HPB (Oxford). 2011 Aug;13(8):528-35. doi: 10.1111/j.1477-2574.2011.00319.x. Epub 2011 Jun 7. Review. — View Citation

Ratti F, Catena M, Di Palo S, Staudacher C, Aldrighetti L. Impact of totally laparoscopic combined management of colorectal cancer with synchronous hepatic metastases on severity of complications: a propensity-score-based analysis. Surg Endosc. 2016 Nov;30(11):4934-4945. Epub 2016 Mar 4. — View Citation

Schiffman SC, Kim KH, Tsung A, Marsh JW, Geller DA. Laparoscopic versus open liver resection for metastatic colorectal cancer: a metaanalysis of 610 patients. Surgery. 2015 Feb;157(2):211-22. doi: 10.1016/j.surg.2014.08.036. Epub 2014 Oct 1. — View Citation

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015 Jan-Feb;65(1):5-29. doi: 10.3322/caac.21254. Epub 2015 Jan 5. — View Citation

Slankamenac K, Nederlof N, Pessaux P, de Jonge J, Wijnhoven BP, Breitenstein S, Oberkofler CE, Graf R, Puhan MA, Clavien PA. The comprehensive complication index: a novel and more sensitive endpoint for assessing outcome and reducing sample size in randomized controlled trials. Ann Surg. 2014 Nov;260(5):757-62; discussion 762-3. doi: 10.1097/SLA.0000000000000948. — View Citation

Soubrane O, Schwarz L, Cauchy F, Perotto LO, Brustia R, Bernard D, Scatton O. A Conceptual Technique for Laparoscopic Right Hepatectomy Based on Facts and Oncologic Principles: The Caudal Approach. Ann Surg. 2015 Jun;261(6):1226-31. doi: 10.1097/SLA.0000000000000737. — View Citation

Tohme S, Goswami J, Han K, Chidi AP, Geller DA, Reddy S, Gleisner A, Tsung A. Minimally Invasive Resection of Colorectal Cancer Liver Metastases Leads to an Earlier Initiation of Chemotherapy Compared to Open Surgery. J Gastrointest Surg. 2015 Dec;19(12):2199-206. doi: 10.1007/s11605-015-2962-5. Epub 2015 Oct 5. — View Citation

Topal H, Tiek J, Aerts R, Topal B. Outcome of laparoscopic major liver resection for colorectal metastases. Surg Endosc. 2012 Sep;26(9):2451-5. doi: 10.1007/s00464-012-2209-4. Epub 2012 Feb 23. — View Citation

Tranchart H, Dagher I. Laparoscopic liver resection: a review. J Visc Surg. 2014 Apr;151(2):107-15. doi: 10.1016/j.jviscsurg.2013.10.003. Epub 2013 Dec 22. Review. — View Citation

Tranchart H, Fuks D, Vigano L, Ferretti S, Paye F, Wakabayashi G, Ferrero A, Gayet B, Dagher I. Laparoscopic simultaneous resection of colorectal primary tumor and liver metastases: a propensity score matching analysis. Surg Endosc. 2016 May;30(5):1853-62. doi: 10.1007/s00464-015-4467-4. Epub 2015 Aug 15. — View Citation

Untereiner X, Cagniet A, Memeo R, Tzedakis S, Piardi T, Severac F, Mutter D, Kianmanesh R, Marescaux J, Sommacale D, Pessaux P. Laparoscopic hepatectomy versus open hepatectomy for colorectal cancer liver metastases: comparative study with propensity score matching. Hepatobiliary Surg Nutr. 2016 Aug;5(4):290-9. doi: 10.21037/hbsn.2015.12.06. — View Citation

Van Ness P. The concept of risk in biomedical research involving human subjects. Bioethics. 2001 Aug;15(4):364-70. — View Citation

Vanounou T, Steel JL, Nguyen KT, Tsung A, Marsh JW, Geller DA, Gamblin TC. Comparing the clinical and economic impact of laparoscopic versus open liver resection. Ann Surg Oncol. 2010 Apr;17(4):998-1009. doi: 10.1245/s10434-009-0839-0. Epub 2009 Dec 22. — View Citation

Veenhof AA, Vlug MS, van der Pas MH, Sietses C, van der Peet DL, de Lange-de Klerk ES, Bonjer HJ, Bemelman WA, Cuesta MA. Surgical stress response and postoperative immune function after laparoscopy or open surgery with fast track or standard perioperative care: a randomized trial. Ann Surg. 2012 Feb;255(2):216-21. doi: 10.1097/SLA.0b013e31824336e2. — View Citation

Vigano L, Laurent A, Tayar C, Tomatis M, Ponti A, Cherqui D. The learning curve in laparoscopic liver resection: improved feasibility and reproducibility. Ann Surg. 2009 Nov;250(5):772-82. doi: 10.1097/SLA.0b013e3181bd93b2. — View Citation

Wakabayashi G, Cherqui D, Geller DA, Han HS, Kaneko H, Buell JF. Laparoscopic hepatectomy is theoretically better than open hepatectomy: preparing for the 2nd International Consensus Conference on Laparoscopic Liver Resection. J Hepatobiliary Pancreat Sci. 2014 Oct;21(10):723-31. doi: 10.1002/jhbp.139. Epub 2014 Aug 5. — View Citation

Wong-Lun-Hing EM, van Dam RM, van Breukelen GJ, Tanis PJ, Ratti F, van Hillegersberg R, Slooter GD, de Wilt JH, Liem MS, de Boer MT, Klaase JM, Neumann UP, Aldrighetti LA, Dejong CH; ORANGE II Collaborative Group. Randomized clinical trial of open versus laparoscopic left lateral hepatic sectionectomy within an enhanced recovery after surgery programme (ORANGE II study). Br J Surg. 2017 Apr;104(5):525-535. doi: 10.1002/bjs.10438. Epub 2017 Jan 31. — View Citation

Wu WC, Smith TS, Henderson WG, Eaton CB, Poses RM, Uttley G, Mor V, Sharma SC, Vezeridis M, Khuri SF, Friedmann PD. Operative blood loss, blood transfusion, and 30-day mortality in older patients after major noncardiac surgery. Ann Surg. 2010 Jul;252(1):11-7. doi: 10.1097/SLA.0b013e3181e3e43f. — View Citation

* Note: There are 60 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of overall complications using the comprehensive complication Index (CCI)	CCI is calculated using the burden of postoperative complications weighted with a measure of the severity according to the widely accepted Dindo-Clavien classification of postoperative complications and a dedicated CCI calculator.	Within 90 days postoperatively or at any time during hospitalization.
Secondary	Proportion of patients presenting severe postoperative complications	Proportion of patients presenting severe postoperative complications rate as defined by the Clavien-Dindo classification = grade 3 (including mortality) between patients treated with laparoscopic liver resection and those treated with open liver surgery	Within 90 days postoperatively or at any time during hospitalization.
Secondary	Rate of conversion from laparoscopy liver resection to open liver surgery	Conversion is defined as the requirement for laparotomy at any time of the procedure with the exception of the extraction of the resected specimen. Specific data regarding conversion will be noticed from the operative reports. These included the reasons for conversion, the timing of conversion and the type of conversion.	during surgery.
Secondary	Length of hospital stay	Length of hospital stay and occurrence of unplanned readmission after discharge,assessed by hospitalization reports	Within 90 days postoperatively or at any time during hospitalization.
Secondary	Delay of recovery before resuming professional activities.	Delay of recovery before resuming professional activities assessed by PQRS (Postoperative Quality Recovery Scale) including nociceptive domain, emotional domain, cognition domain and day-to-day activities at D-1, D1, D7, D30 and D90.	Within 90 days postoperatively
Secondary	Postoperative quality of life using quality of life questionnaries.	Patient-reported outcome measures were assessed with the validated European Organisation for Research and Treatment of Cancer (EORTC) score questionnaire, EORTC Quality of Life Questionnaire (QLQ) -C30 (version 3.0), and the module dedicated to colorectal liver metastases (EORTC QLQ-LMC21). EQ5D-5L is a standardised measure of health status that provides a simple descriptive profile and a single index value suitable for the economic evaluation of health. It will be used to calculate the QALYs of each enrolled patient, by valuing health.	At the inclusion (before surgery), at 1 month postintervention, 3 months, 6 months and then every 6 months during 3 years.
Secondary	Health economics analysis	A cost-effectiveness study will be performed and completed by a cost-utility analysis to identify the efficient therapeutic strategy (laparoscopic approach) ompared to the reference (open surgery).; Only direct costs will be considered for treatments, management of side effects, medical transports, rehabilitation procedures and medical consultations.; Out of hospital resources are valued from the Social Health Insurance (SHI) tariffs and hospital stays the Diagnosis-Related group (DRG) tariff taking into account additional daily fixed prices for ICU stay, if any.	During the full participation period (3 years).
Secondary	Oncologic quality of the resection using the pathological report.	Mean surgical margin widths (in millimeters). Percentages of microscopically complete (R0), microscopically incomplete (R1) and macroscopically incomplete (R2) resections as stated in the pathological report.	During surgery
Secondary	Disease-free and overall survival at 3 years.	Percentage of patients with intrahepatic or extrahepatic recurrence three years after the operation.; Median disease-free survival time (in months).; Percentage of patients who died at 1, 2 and 3 years after the procedure.; Median overall survival time (in months).	During the full participation period (3 years).