EClinicalMedicine (May 2023)

Surgical outcomes of gallbladder cancer: the OMEGA retrospective, multicentre, international cohort studyResearch in context

  • Anita Balakrishnan,
  • Petros Barmpounakis,
  • Nikolaos Demiris,
  • Asif Jah,
  • Harry V.M. Spiers,
  • Shibojit Talukder,
  • Jack L. Martin,
  • Paul Gibbs,
  • Simon J.F. Harper,
  • Emmanuel L. Huguet,
  • Vasilis Kosmoliaptsis,
  • Siong S. Liau,
  • Raaj K. Praseedom,
  • Bristi Basu,
  • Xavier de Aretxabala,
  • Javier Lendoire,
  • Shishir Maithel,
  • Alejandro Branes,
  • Bodil Andersson,
  • Alejandro Serrablo,
  • Volkan Adsay,
  • Tomoyuki Abe,
  • Moh'd Abu Hilal,
  • Maria del Mar Achalandabaso Boira,
  • Mustapha Adham,
  • Mohamed Adam,
  • Maryam Ahmad,
  • Bilal Al-Sarireh,
  • Maite Albiol,
  • Nassir Alhaboob,
  • Adnan Alseidi,
  • Houssem Ammar,
  • Akshay Anand,
  • Bodil Andersson,
  • Pantelis Antonakis,
  • Veronica Araya,
  • Stanley W. Ashley,
  • Georgi Atanasov,
  • Fabio Ausania,
  • Ricardo Balestri,
  • Abhirup Banerjee,
  • Simon Banting,
  • Giedrius Barauskas,
  • Fabian Bartsch,
  • Andrea Belli,
  • Simona Beretta,
  • Frederik Berrevoet,
  • Gerardo Blanco Fernandez,
  • Louisa Bolm,
  • Mathieu Bonal,
  • Emre Bozkurt,
  • Andries E. Braat,
  • Luke Bradshaw,
  • Alejandro Branes,
  • Lyle Burdine,
  • Matthew Byrne,
  • Maria Caceres,
  • Maria Jesus Castro Santiago,
  • Benjamin Chan,
  • Lynn Chong,
  • Ahmet Çoker,
  • Maria Conde Rodriguez,
  • Daniel Croagh,
  • Alyn Crutchley,
  • Carmen Cutolo,
  • Mathieu D'Hondt,
  • Daniel D'Souza,
  • Freek Daams,
  • Raffaele Dalla Valle,
  • José Davide,
  • Mario de Bellis,
  • Marieke de Boer,
  • Celine de Meyere,
  • Philip de Reuver,
  • Matthew Dixon,
  • Panagiotis Dorovinis,
  • Gabriela Echeverría Bauer,
  • Maria Eduarda,
  • Hasan Eker,
  • Joris Erdmann,
  • Mert Erkan,
  • Evangelos Felekouras,
  • Emanuele Felli,
  • Eduardo Fernandes,
  • Eduardo Figueroa Rivera,
  • Andras Fulop,
  • Daniel Galun,
  • Michael Gerhards,
  • Poya Ghorbani,
  • Fabio Giannone,
  • Luis Gil,
  • Emmanouil Giorgakis,
  • Mario Giuffrida,
  • Felice Giuliante,
  • Ioannis Gkekas,
  • Miguel Gomez Bravo,
  • Bas Groot Koerkamp,
  • Oscar Guevara,
  • Alfredo Guglielmi,
  • Aiste Gulla,
  • Rahul Gupta,
  • Amit Gupta,
  • Marta Gutiérrez,
  • Abu Bakar Hafeez Bhatti,
  • Jeroen Hagendoorn,
  • Zain Hajee,
  • Abdul Rahman Hakeem,
  • Hytham Hamid,
  • Sayed Hassen,
  • Stefan Heinrich,
  • Ryota Higuchi,
  • Daniel Hoffman,
  • David Holroyd,
  • Daniel Hughes,
  • Arpad Ivanecz,
  • Satheesh Iype,
  • Isabel Jaen Torrejimeno,
  • Shantanu Joglekar,
  • Robert Jones,
  • Klaus Kaczirek,
  • Harsh Kanhere,
  • Ambareen Kausar,
  • Zhanyi Kee,
  • Jessica Keilson,
  • Jorg Kleef,
  • Johannes Klose,
  • Brett Knowles,
  • Jun Kit Koong,
  • Nagappan Kumar,
  • Supreeth Kunnuru,
  • Paleswan Joshi Lakhey,
  • Andrea Laurenzi,
  • Yeong Sing Lee,
  • Felipe Leon,
  • Voon Meng Leow,
  • Jean-Baptiste Lequeu,
  • Mickael Lesurtel,
  • Elisabeth Lo,
  • Stefan Löb,
  • Elizabeth Lockie,
  • Peter Lodge,
  • Dolores López Garnica,
  • Victor Lopez Lopez,
  • Linda Lundgren,
  • Nikolaos Machairas,
  • Dhiresh Maharjan,
  • Deep Malde,
  • Guillaume Martel,
  • Julie Martin,
  • Michele Mazzola,
  • Arianeb Mehrabi,
  • Ricardo Memeo,
  • Flavio Milana,
  • George Molina,
  • Leah Monette,
  • Haluk Morgul,
  • Dimitrios Moris,
  • Antonios Morsi-Yeroyannis,
  • Nicholas Mowbray,
  • Francesk Mulita,
  • Edoardo Maria Muttillo,
  • Malith Nandasena,
  • Pueya Rashid Nashidengo,
  • Arash Nickkholgh,
  • Colin Byron Noel,
  • Masayuki Ohtsuka,
  • Arturs Ozolins,
  • Sanjay Pandanaboyana,
  • Nikolaos Pararas,
  • Alessandro Parente,
  • June Peng,
  • Arkaitz Perfecto Valero,
  • Julie Perinel,
  • Konstatinos Perivoliotis,
  • Teresa Perra,
  • Patrick Pessaux,
  • Natalie Petruch,
  • Gaetano Piccolo,
  • Laszlo Piros,
  • Alberto Porcu,
  • Viswakumar Prabakaran,
  • Raj Prasad,
  • Mikel Prieto Calvo,
  • Florian Primavesi,
  • Eva Maria Pueyo Periz,
  • Alberto Quaglia,
  • Jose M. Ramia Angel,
  • Ashwin Rammohan,
  • Francisco Razionale,
  • Ricardo Robles Campos,
  • Manas Roy,
  • Sophie Rozwadowski,
  • Luis Ruffolo,
  • Natalia Ruiz,
  • Andrea Ruzzenante,
  • Lily Saadat,
  • Mohamed Amine Said,
  • Edoardo Saladino,
  • Gabriel Saliba,
  • Per Sandstrom,
  • Carlo Alberto Schena,
  • Anthony Scholer,
  • Cristoph Schwartz,
  • Lorenzo Serafini,
  • Pablo Serrano,
  • Deepak Sharma,
  • Aali Sheen,
  • Vishwanath Siddagangaiah,
  • Michael Silva,
  • Saurabh Singh,
  • Ajith Siriwardena,
  • Michal Skalski,
  • Mante Smig,
  • Faris Soliman,
  • Donzília Sousa Silva,
  • Ernesto Sparrelid,
  • Parthi Srinivasan,
  • Malin Sternby Eilard,
  • Oliver Strobel,
  • Urban Stupan,
  • Miguel Angel Suarez-Munoz,
  • Manisekar Subramaniam,
  • Teiichi Sugiura,
  • Robert Sutcliffe,
  • Hilko Swank,
  • Lillian Taylor,
  • Prabin Bikram Thapa,
  • Catherine The,
  • Asara Thepbunchonchai,
  • Caman Thieu,
  • Navneet Tiwari,
  • Guido Torzilli,
  • Chutwichai Tovikkai,
  • Blaz Trotovsek,
  • Savvas Tsaramanidis,
  • Georgios Tsoulfas,
  • Katsuhiko Uesaka,
  • Garzali Umar,
  • Lucio Urbani,
  • Michail Vailas,
  • Ronald van Dam,
  • Peter van de Boezem,
  • Stijn van Laarhoven,
  • Tomas Vanagas,
  • Mike Van Dooren,
  • Manon Viannet,
  • Luca Vigano,
  • Aarathi Vijayashanker,
  • Celia Villodre,
  • Toshifumi Wakai,
  • Aklile Workneh,
  • Li Xu,
  • Masakazu Yamamoto,
  • Zhiying Yang,
  • Robert Young,
  • Marko Zivanovic

Journal volume & issue
Vol. 59
p. 101951

Abstract

Read online

Summary: Background: Gallbladder cancer (GBC) is rare but aggressive. The extent of surgical intervention for different GBC stages is non-uniform, ranging from cholecystectomy alone to extended resections including major hepatectomy, resection of adjacent organs and routine extrahepatic bile duct resection (EBDR). Robust evidence here is lacking, however, and survival benefit poorly defined. This study assesses factors associated with recurrence-free survival (RFS), overall survival (OS) and morbidity and mortality following GBC surgery in high income countries (HIC) and low and middle income countries (LMIC). Methods: The multicentre, retrospective Operative Management of Gallbladder Cancer (OMEGA) cohort study included all patients who underwent GBC resection across 133 centres between 1st January 2010 and 31st December 2020. Regression analyses assessed factors associated with OS, RFS and morbidity. Findings: On multivariable analysis of all 3676 patients, wedge resection and segment IVb/V resection failed to improve RFS (HR 1.04 [0.84–1.29], p = 0.711 and HR 1.18 [0.95–1.46], p = 0.13 respectively) or OS (HR 0.96 [0.79–1.17], p = 0.67 and HR 1.48 [1.16–1.88], p = 0.49 respectively), while major hepatectomy was associated with worse RFS (HR 1.33 [1.02–1.74], p = 0.037) and OS (HR 1.26 [1.03–1.53], p = 0.022). Furthermore, EBDR (OR 2.86 [2.3–3.52], p < 0.0010), resection of additional organs (OR 2.22 [1.62–3.02], p < 0.0010) and major hepatectomy (OR 3.81 [2.55–5.73], p < 0.0010) were all associated with increased morbidity and mortality. Compared to LMIC, patients in HIC were associated with poorer RFS (HR 1.18 [1.02–1.37], p = 0.031) but not OS (HR 1.05 [0.91–1.22], p = 0.48). Adjuvant and neoadjuvant treatments were infrequently used. Interpretation: In this large, multicentre analysis of GBC surgical outcomes, liver resection was not conclusively associated with improved survival, and extended resections were associated with greater morbidity and mortality without oncological benefit. Aggressive upfront resections do not benefit higher stage GBC, and international collaborations are needed to develop evidence-based neoadjuvant and adjuvant treatment strategies to minimise surgical morbidity and prioritise prognostic benefit. Funding: Cambridge Hepatopancreatobiliary Department Research Fund.

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