TY - JOUR
T1 - Surgical outcomes of gallbladder cancer
T2 - the OMEGA retrospective, multicentre, international cohort study
AU - Balakrishnan, Anita
AU - Barmpounakis, Petros
AU - Demiris, Nikolaos
AU - Jah, Asif
AU - Spiers, Harry V. M.
AU - Talukder, Shibojit
AU - Martin, Jack L.
AU - Gibbs, Paul
AU - Harper, Simon J. F.
AU - Huguet, Emmanuel L.
AU - Kosmoliaptsis, Vasilis
AU - Liau, Siong S.
AU - Praseedom, Raaj K.
AU - Basu, Bristi
AU - de Aretxabala, Xavier
AU - Lendoire, Javier
AU - Maithel, Shishir
AU - The OMEGA Study Investigators
AU - Branes, Alejandro
AU - Andersson, Bodil
AU - Serrablo, Alejandro
AU - Adsay, Volkan
AU - Abe, Tomoyuki
AU - Abu Hilal, Moh'd
AU - Achalandabaso Boira, Maria del Mar
AU - Adham, Mustapha
AU - Adam, Mohamed
AU - Ahmad, Maryam
AU - Al-Sarireh, Bilal
AU - Albiol, Maite
AU - Alhaboob, Nassir
AU - Alseidi, Adnan
AU - Ammar, Houssem
AU - Anand, Akshay
AU - Antonakis, Pantelis
AU - Araya, Veronica
AU - Ashley, Stanley W.
AU - Atanasov, Georgi
AU - Ausania, Fabio
AU - Balestri, Ricardo
AU - Banerjee, Abhirup
AU - Banting, Simon
AU - Barauskas, Giedrius
AU - Bartsch, Fabian
AU - Belli, Andrea
AU - Daams, Freek
AU - de Boer, Marieke
AU - Eker, Hasan
AU - Erdmann, Joris
AU - Gerhards, Michael
AU - Swank, Hilko
N1 - Funding Information: We thank Ms Carrie Hooper and Dr Adam Duckworth for their help with this study, and Prof Robert Tasker for his contribution to this manuscript. Funding for the statistical analyses was provided by the Cambridge Hepatopancreatobiliary Department Research Fund . Funding Information: SM has the following interests: 1) Principal investigator of a clinical trial on intrahepatic cholangiocarcinoma funded by BMS/Celgene (grant funding provided to institution, no personal compensation) 2) Advisory board member at Astra Zeneca on management of hepatocellular carcinoma and 3) Scientific Medical Advisory Board member Cholangiocarcinoma Foundation. Publisher Copyright: © 2023 The Author(s)
PY - 2023/5/1
Y1 - 2023/5/1
N2 - 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.
AB - 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.
KW - Cholangiocarcinoma
KW - Gallbladder cancer
KW - Liver resection
KW - Surgical outcomes
UR - http://www.scopus.com/inward/record.url?scp=85152300811&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.eclinm.2023.101951
DO - https://doi.org/10.1016/j.eclinm.2023.101951
M3 - Article
C2 - 37125405
SN - 2589-5370
VL - 59
JO - EClinicalMedicine
JF - EClinicalMedicine
M1 - 101951
ER -