Retrospective Cohort Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 14, 2022; 28(18): 1996-2007
Published online May 14, 2022. doi: 10.3748/wjg.v28.i18.1996
Incidental gallbladder cancer diagnosis confers survival advantage irrespective of tumour stage and characteristics
Moath Alarabiyat, Syed Soulat Raza, John Isaac, Darius Mirza, Ravi Marudanayagam, Keith Roberts, Manuel Abradelo, David C Bartlett, Bobby V Dasari, Robert P Sutcliffe, Nikolaos A Chatzizacharias
Moath Alarabiyat, Syed Soulat Raza, John Isaac, Darius Mirza, Ravi Marudanayagam, Keith Roberts, Manuel Abradelo, David C Bartlett, Bobby V Dasari, Robert P Sutcliffe, HPB and Liver Transplant Unit, Queen Elizabeth Hospital, Birmingham B15 2GW, United Kingdom
Nikolaos A Chatzizacharias, Department of HPB and Liver Transplantation, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2TH, United Kingdom
Author contributions: Alarabiyat M and Raza SS are responsible for the data collection, statistical analysis, and wrote the manuscript; Alarabiyat M did the statistical analysis; Isaac J, Mirza DF, Marudanayagam R, Roberts K, Abradelo M, Bartlett DC, Dasari B, Sutcliffe BP are responsible for interpretation of data, manuscript revision and editing, approval of finalized version of the manuscript; Chatzizacharias N is responsible for developed research concept, writing, manuscript preparation, editing and review.
Institutional review board statement: The study was approved by the departmental ethics committee.
Informed consent statement: As this was an anonymised retrospective cohort study over a period of 12 years, individual consent forms were not required based on the policy of Queen Elizabeth Hospital and the UK on ethics and research.
Conflict-of-interest statement: The authors have no conflicts of interest to disclose.
Data sharing statement: The original dataset is anonymized and available upon request from the corresponding author at Nikolaos.chatzizacharias@uhb.nhs.net.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Nikolaos A Chatzizacharias, FACS, FRCS, MD, PhD, Surgeon, Department of HPB and Liver Transplantation, Queen Elizabeth Hospital, University Hospitals Birmingham, Third Floor, Nuffield House, Mindelsohn Way, Birmingham B15 2TH, United Kingdom. chatzizacharias@gmail.com
Received: November 13, 2021
Peer-review started: November 13, 2021
First decision: January 9, 2022
Revised: January 22, 2022
Accepted: March 26, 2022
Article in press: March 26, 2022
Published online: May 14, 2022
Processing time: 179 Days and 20.6 Hours
ARTICLE HIGHLIGHTS
Research background

Incidental gallbladder cancer (IGBC) represents 50%-60% of gallbladder cancer cases. Data are conflicting on the role of IGBC diagnosis in oncological outcomes. Some studies suggest that IGBC diagnosis does not affect outcomes, while others that overall survival (OS) is longer in these cases compared to non-incidental diagnosis (NIGBC). Furthermore, some studies reported early tumour stages and histopathologic characteristics as possible confounders, while others not.

Research motivation

GB cancer is an uncommon malignancy with poor survival. Data suggest whether the diagnosis is incidental or not may play a role in the oncological outcomes. Confirmation of this observation may lead in further research aiming to better identify the reasons and refining the treatment strategy based on the presenting diagnosis.

Research objectives

This study aimed to investigate the role of IGBC diagnosis on patients’ overall survival, especially after surgical treatment with curative intent.

Research methods

This is a retrospective analysis of all patient referrals with gallbladder cancer between 2008 and 2020 in a tertiary hepatobiliary centre. All patients had complete staging and were discussed in the multidisciplinary meeting prior to deciding on the treatment plan. Demographic, surgical and tumour variables were collected and compared between patients with IGBC and NIGBC using the appropriate statistical tests. Survival curves for OS and DFS were created using Kaplan-Meier method and compared with the log rank test. Risk analysis for independent predictors of OS and DFS was performed with univariable time to event analysis using the Cox proportional hazard model. Factors with a P value of < 0.200 were entered into a multivariable model and independent predictors (those with P < 0.05) were indentified. All statistical analysis was done using the software SPSS for Windows (Version 25.0, SPSS Inc., Chicago, IL, United States).

Research results

261 patients with GB cancer were included. Almost one-third pf patients had IGBC (91/261 patients) and two-thirds had NIGC. A total of 90/261 (34%) patients proceeded to have oncological resection. Metastatic disease was the most common reason for not having oncological resection. Patients with NIGBC were more likely to have advanced T stages of the disease and required more extensive resections than patients with IGBC. Survival analysis shows that patients with IGBC had better OS than patients with NIGBC in the whole cohort (29 vs 4 mo, P < 0.001), as well as in the non-surgical (14 vs 2 mo, P < 0.001) and surgical subgroups (29 vs 16.5 mo, P = 0.001). DFS was similarly better in patients with IGBC who underwent oncological resection (21.5 mo vs 8.5 mo, P = 0.007). After univariable and multivariable risk analysis, N stage, resection margin status and non-incidental diagnosis were identified as independent predictors of OS. N stage and resection margin status were also independent predictors of DFS. Within the limitations of a retrospective single centre study, our data suggest that difference in the oncological outcomes between the two groups cannot be solely explained by differences in pathologic or tumour features.

Research conclusions

Our study suggests that IGBC diagnosis may confer a survival advantage, including patients that received surgical treatment, independently of the pathological stage and tumour characteristics. Prospective studies are required to investigate the reasons behind this, including detailed pathological analysis and molecular gene expression.

Research perspectives

Published evidence is still contradicting. The theory that IGBC and NIGBC are two distinct variants of the same disease remains to be proven by detailed pathologic assessment and research in cancer molecular genetics.