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Surgical outcomes of gallbladder cancer: the OMEGA retrospective, multicentre, international cohort study

Balakrishnan, A. ; Andersson, B. LU orcid and Adsay, V. (2023) In EClinicalMedicine 59.
Abstract
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... (More)
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. © 2023 The Author(s) (Less)
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keywords
Cholangiocarcinoma, Gallbladder cancer, Liver resection, Surgical outcomes, antineoplastic agent, adjuvant chemotherapy, adjuvant therapy, adult, aged, Article, cancer prognosis, cancer staging, cancer surgery, cancer survival, cholecystectomy, cohort analysis, controlled study, disease association, extrahepatic bile duct, female, follow up, gallbladder cancer, hepatectomy, high income country, human, human tissue, liver histology, low income country, major clinical study, male, middle income country, morbidity, mortality, outcome assessment, overall survival, recurrence free survival, regression analysis, retrospective study, treatment outcome, wedge resection
in
EClinicalMedicine
volume
59
article number
101951
publisher
Lancet Publishing Group
external identifiers
  • scopus:85152300811
  • pmid:37125405
ISSN
2589-5370
DOI
10.1016/j.eclinm.2023.101951
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English
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yes
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Number of authors = 255 EID = 85152300811 Article no = 101951 Affiliation = Balakrishnan, A., Department of HPB Surgery, Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge, CB2 0QQ, United Kingdom Affiliation = Zivanovic, M. Affiliation = The OMEGA Study Investigators
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0d5f755e-6ed0-417f-9538-eda4b44064ac
date added to LUP
2023-11-06 13:42:45
date last changed
2023-11-07 03:00:07
@article{0d5f755e-6ed0-417f-9538-eda4b44064ac,
  abstract     = {{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 &lt; 0.0010), resection of additional organs (OR 2.22 [1.62–3.02], p &lt; 0.0010) and major hepatectomy (OR 3.81 [2.55–5.73], p &lt; 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. © 2023 The Author(s)}},
  author       = {{Balakrishnan, A. and Andersson, B. and Adsay, V.}},
  issn         = {{2589-5370}},
  keywords     = {{Cholangiocarcinoma; Gallbladder cancer; Liver resection; Surgical outcomes; antineoplastic agent; adjuvant chemotherapy; adjuvant therapy; adult; aged; Article; cancer prognosis; cancer staging; cancer surgery; cancer survival; cholecystectomy; cohort analysis; controlled study; disease association; extrahepatic bile duct; female; follow up; gallbladder cancer; hepatectomy; high income country; human; human tissue; liver histology; low income country; major clinical study; male; middle income country; morbidity; mortality; outcome assessment; overall survival; recurrence free survival; regression analysis; retrospective study; treatment outcome; wedge resection}},
  language     = {{eng}},
  publisher    = {{Lancet Publishing Group}},
  series       = {{EClinicalMedicine}},
  title        = {{Surgical outcomes of gallbladder cancer: the OMEGA retrospective, multicentre, international cohort study}},
  url          = {{http://dx.doi.org/10.1016/j.eclinm.2023.101951}},
  doi          = {{10.1016/j.eclinm.2023.101951}},
  volume       = {{59}},
  year         = {{2023}},
}