Clinicopathological prognostic factors for gallbladder carcinoma: a retrospective study

Abstract

Background: Gallbladder carcinoma (GBC) is an uncommon neoplasm with poor long-term survival. Worldwide the incidence rates vary according to geographic area. The multifactorial aetiology and the rarity of the disease limits the studies to improve outcomes in patients, since the treatment remains mostly surgical. The aim of this study was to identify clinicopathological prognostic factors for survival in patients with GBC submitted to surgery in our institution-a tertiary centre in Portugal. Also, to assess the expression of possible biomarkers (HER2, CD44 and ALDH1) in GBC, as well as the frequency of microsatellite instability (MSI) tumours.Methods: Clinicopathological characteristics of 41 consecutive patients that underwent surgical resection for GBC (2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015)(2016)(2017)(2018)(2019) at our hospital were retrospectively reviewed. Clinicopathological factors were assessed and an immunohistochemical (IHC) analysis was done. Microsatellite stability (MSS) was considered if there was maintenance of nuclear expression of MLH1, MSH2, MSH6 and PMS2. Human epidermal growth factor receptor 2 (HER2) expression was evaluated according to the rules applied for gastric cancer and expression of CD44 and ALH1 was evaluated in order to detect cancer stem cells (CSC). Survival analysis was conducted using Kaplan-Meier and Cox regression was used to find prognostic factors.Results: Incidence of GBC in our cohort of patients was 0.45%, most commonly affecting females. Median overall survival (OS) was 23 months with a 39.6% 5-year survival rate. Stage > II [hazard ratios (HR) =8.58; P=0.007], lymphovascular invasion (LVI) (HR =4.06; P=0.045) and hepatic resection (HR =0.288; P=0.034) independently influenced survival. HER2 positivity and high expression of CD44 or ADLH1 did not show significant influence in survival (P=0.649, P=0.868 and P=0.914, respectively), although HER2 and ALDH1 positive patients showed a tendency to a shorter OS, compared to negative patients. We found no relation between these biomarkers expression and disease stage. All analysed samples had MSS.Conclusions: GBC patients with a worse prognosis can be identified. The overexpression of HER2 could select patients for targeted therapy and prompt tissue sampling in unresectable patients.

"Analyzing Survival Predictors and Treatment Strategies in Gallbladder Cancer: A Comprehensive Survival Analysis Study": Single center experience over 10 years

“…Existing literature highlights signi cant survival disparities between node-negative and node-positive diseases, with 5-year survival rates ranging from 58% -77% for the former, in contrast to 0% − 45% for the latter [9]. Regional lymph node involvement is observed in 19-62% of T2 tumours and 75-85% of T3/T4 tumours, while N2 lymph node involvement is noted in 18-36% of T2 tumours and 42-71% of T3/T4 tumours [22,27]. Our study's ndings align closely with these previous reports, as the rate of lymph node positivity increased with higher pT stages: 0% in T1, 17% in T2, 54% in T3, and 100% in T4.…”

Effects of cytoreductive surgery combined with hyperthermic perfusion chemotherapy on prognosis of patients with advanced gallbladder cancer

“…During surgery, instruments may touch cancer cells at the margin, causing them to fall off and form an implantation metastasis[ 19 ]. Additionally, tumor dissection can sometimes increase intraperitoneal spread and growth of GC cells owing to their aggressive invasion and adhesion or growth variation.…”

“…The tumor stage, distant metastasis, and treatment plan were independent factors affecting prognosis. Many reports have suggested a correlation between tumor stage, distant metastasis, and prognosis in patients with advanced GC[ 19 , 25 , 26 ]. This study found that CRS combined with HIPEC improves the survival time, indicating that this combination is safe and effective.…”

TRIM37 promotes gallbladder cancer proliferation by activating the Wnt/β-catenin pathway via ubiquitination of Axin1

“…GBC is the most common cancer in the biliary tract characterized by high mortality rates, late diagnosis and poor clinical presentation [ 14 , 15 ]. Despite advances in GBC therapy, the prognosis for most patients remains dismal.…”