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Recent epidemiological studies suggested that proton pump inhibitor (PPI) use was associated with an increased risk of biliary tract cancer (BTC), however, confounders were not adequately controlled. Our study aimed to evaluate PPI use and subsequent risk of BTC and its subtypes in three well‐established cohorts. We conducted a pooled analysis of the subjects free of cancers in UK Biobank (n = 463 643), Nurses' Health Study (NHS, n = 80 235) and NHS II (n = 95 869). Propensity score weighted Cox models were used to estimate marginal HRs of PPIs use on BTC risk, accounting for potential confounders. We documented 284 BTC cases in UK Biobank (median follow‐up: 7.6 years), and 91 cases in NHS and NHS II cohorts (median follow‐up: 15.8 years). In UK biobank, PPI users had a 96% higher risk of BTC compared to nonusers in crude model (HR 1.96, 95% CI 1.44‐2.66), but the effect was attenuated to null after adjusting for potential confounders (HR 0.95, 95% CI 0.60‐1.49). PPI use was not associated with risk of BTC in the pooled analysis of three cohorts (HR 0.93, 95% CI 0.60‐1.43). We also observed no associations between PPI use with risk of intrahepatic (HR 1.00, 95% CI 0.49‐2.04), extrahepatic bile duct (HR 1.09, 95% CI 0.52‐2.27) and gallbladder cancers (HR 0.66, 95% CI 0.26‐1.66) in UK Biobank. In summary, regular use of PPIs was not associated with the risk of BTC and its subtypes. [ABSTRACT FROM AUTHOR]

Introduction and objectives: Gallbladder disease is a common disease with high prevalence. Majority of gallbladder disease is due to gallstone. Though genetics are believed to play a role in its pathogenesis, the contribution of environmental pressures in early life to the development of this disease in adulthood has not been ever investigated. This study aimed to clarify the risk of maternal smoking exposure in association with gallbladder disease in adulthood. The interaction of maternal smoking and own smoking during adulthood on this association was studied as well. Patients and methods: A total of 286,731 eligible participants from the UK Biobank population-based cohort were included. Multivariable Cox regression analysis were used to examine the HR and 95% CI with adjustment for covariates. Result: During a median of 8.8 years follow-up, 7110 incident cases of gallbladder disease including 6800 (95.6%) gallstone were identified. Maternal smoking was associated with increased risk of incident total gallbladder disease (HR = 1.13; 95%CI: 1.06 - 1.21; P = 0.0002) as well as gallstones (HR = 1.13; 95%CI: 1.06 -1.21; P = 0.0003) in adulthood. Compared with those who were neither exposed to maternal smoking nor own smoking, subjects adherence to no smoking during adulthood but having maternal smoking exposure still had increased risk of total gallbladder disease (HR = 1.21; 95%CI: 1.1-1.34, P=0.0001) and gallstones (HR = 1.21; 95%CI: 1.1-1.35, P=0.0001). Conclusion: The present study using large prospective cohort data from UK Biobank, for the first time, demonstrated maternal smoking exposure bringing elevated risk of incident total gallbladder disease/gallstone in adulthood. [ABSTRACT FROM AUTHOR]

Background: Advanced biliary tract cancer has a poor prognosis. Cisplatin and gemcitabine is the standard first-line chemotherapy regimen, but no robust evidence is available for second-line chemotherapy. The aim of this study was to determine the benefit derived from second-line FOLFOX (folinic acid, fluorouracil, and oxaliplatin) chemotherapy in advanced biliary tract cancer.Methods: The ABC-06 clinical trial was a phase 3, open-label, randomised trial done in 20 sites with expertise in managing biliary tract cancer across the UK. Adult patients (aged ≥18 years) who had histologically or cytologically verified locally advanced or metastatic biliary tract cancer (including cholangiocarcinoma and gallbladder or ampullary carcinoma) with documented radiological disease progression to first-line cisplatin and gemcitabine chemotherapy and an Eastern Cooperative Oncology Group performance status of 0-1 were randomly assigned (1:1) centrally to active symptom control (ASC) and FOLFOX or ASC alone. FOLFOX chemotherapy was administered intravenously every 2 weeks for a maximum of 12 cycles (oxaliplatin 85 mg/m2, L-folinic acid 175 mg [or folinic acid 350 mg], fluorouracil 400 mg/m2 [bolus], and fluorouracil 2400 mg/m2 as a 46-h continuous intravenous infusion). Randomisation was done following a minimisation algorithm using platinum sensitivity, serum albumin concentration, and stage as stratification factors. The primary endpoint was overall survival, assessed in the intention-to-treat population. Safety was also assessed in the intention-to-treat population. The study is complete and the final results are reported. This trial is registered with ClinicalTrials.gov, NCT01926236, and EudraCT, 2013-001812-30.Findings: Between March 27, 2014, and Jan 4, 2018, 162 patients were enrolled and randomly assigned to ASC plus FOLFOX (n=81) or ASC alone (n=81). Median follow-up was 21·7 months (IQR 17·2-30·8). Overall survival was significantly longer in the ASC plus FOLFOX group than in the ASC alone group, with a median overall survival of 6·2 months (95% CI 5·4-7·6) in the ASC plus FOLFOX group versus 5·3 months (4·1-5·8) in the ASC alone group (adjusted hazard ratio 0·69 [95% CI 0·50-0·97]; p=0·031). The overall survival rate in the ASC alone group was 35·5% (95% CI 25·2-46·0) at 6 months and 11·4% (5·6-19·5) at 12 months, compared with 50·6% (39·3-60·9) at 6 months and 25·9% (17·0-35·8) at 12 months in the ASC plus FOLFOX group. Grade 3-5 adverse events were reported in 42 (52%) of 81 patients in the ASC alone group and 56 (69%) of 81 patients in the ASC plus FOLFOX group, including three chemotherapy-related deaths (one each due to infection, acute kidney injury, and febrile neutropenia). The most frequently reported grade 3-5 FOLFOX-related adverse events were neutropenia (ten [12%] patients), fatigue or lethargy (nine [11%] patients), and infection (eight [10%] patients).Interpretation: The addition of FOLFOX to ASC improved median overall survival in patients with advanced biliary tract cancer after progression on cisplatin and gemcitabine, with a clinically meaningful increase in 6-month and 12-month overall survival rates. To our knowledge, this trial is the first prospective, randomised study providing reliable, high-quality evidence to allow an informed discussion with patients of the potential benefits and risks from second-line FOLFOX chemotherapy in advanced biliary tract cancer. Based on these findings, FOLFOX should become standard-of-care chemotherapy in second-line treatment for advanced biliary tract cancer and the reference regimen for further clinical trials.Funding: Cancer Research UK, StandUpToCancer, AMMF (The UK Cholangiocarcinoma Charity), and The Christie Charity, with additional funding from The Cholangiocarcinoma Foundation and the Conquer Cancer Foundation Young Investigator Award for translational research. [ABSTRACT FROM AUTHOR]

Cystic fibrosis (CF) carriers carrying one defective copy of a CFTR germline mutation are common in the general population. A recent study reported associations of CF carriers with risk for cancers of digestive organs and pancreatic cancer. In the current study, we assessed associations of CFTR F508del carriers with the risk for 54 types of cancers in the UK Biobank, a large population‐based study. In Caucasians, compared to the carrier rate of 3.15% (12 357/392274) in noncancer subjects, the rate was significantly higher in cancer patients overall (2621/79619 = 3.29%), especially in patients with colorectal cancer (247/6667 = 3.70%), cancers of gallbladder and biliary tract (21/351 = 5.98%), thyroid cancer (30/665 = 4.51%) and unspecified non‐Hodgkin's lymphoma (74/1805 = 4.10%), all P ≤.05. In contrast, the carrier rate in patients with cancers of lung and bronchus was significantly lower (89/3463 = 2.57%), P =.05. The association of CFTR F508del carriers with these types of cancer remained significant after adjusting for respective cancer‐specific risk factors. For pancreatic cancer, although a higher carrier rate (38/1004 = 3.78%) was found in patients with this cancer, the difference was not statistically significant (P =.26). This null association was unlikely due to lack of statistical power; the large sample size of our study had >80% power, at a significance level of.05, to detect an association of >1.5‐fold increased risk. In conclusion, the identified associations of CFTR F508del carriers with multiple types of cancer may have potential biological and clinical implications if confirmed in independent study populations. What's new? Cystic fibrosis (CF) carriers have only one defective copy of the CFTR gene. While this means that carriers do not develop CF, they may be at increased risk of CF‐related conditions, including cancer. Here, using data from the population‐based UK Biobank study, the authors investigated potential associations between CFTR F508del, the most common CFTR mutation, and risk of 54 cancer types. The CFTR F508del carrier rate was found to be significantly elevated in several types of cancer, including colorectal and gallbladder/biliary tract cancers, thyroid cancer, and unspecified non‐Hodgkin's lymphoma. The findings may be relevant for risk stratification among CF carriers. [ABSTRACT FROM AUTHOR]

Background: Adiposity is a strong risk factor for cancer incidence and mortality. However, most of the evidence available has focused on body mass index (BMI) as a marker of adiposity. There is limited evidence on relationships of cancer with other adiposity markers, and if these associations are linear or not. The aim of this study was to investigate the associations of six adiposity markers with incidence and mortality from 24 cancers by accounting for potential non-linear associations.Methods: A total of 437,393 participants (53.8% women; mean age 56.3 years) from the UK Biobank prospective cohort study were included in this study. The median follow-up was 8.8 years (interquartile range 7.9 to 9.6) for mortality and 9.3 years (IQR 8.6 to 9.9) for cancer incidence. Adiposity-related exposures were BMI, body fat percentage, waist-hip ratio, waist-height ratio, and waist and hip circumference. Incidence and mortality of 24 cancers sites were the outcomes. Cox proportional hazard models were used with each of the exposure variables fitted separately on penalised cubic splines.Results: During follow-up, 47,882 individuals developed cancer and 11,265 died due to cancer during the follow-up period. All adiposity markers had similar associations with overall cancer incidence. BMI was associated with a higher incidence of 10 cancers (stomach cardia (hazard ratio per 1 SD increment 1.35, (95% CI 1.23; 1.47)), gallbladder (1.33 (1.12; 1.58)), liver (1.27 (1.19; 1.36)), kidney (1.26 (1.20; 1.33)), pancreas (1.12 (1.06; 1.19)), bladder (1.09 (1.04; 1.14)), colorectal (1.10 (1.06; 1.13)), endometrial (1.73 (1.65; 1.82)), uterine (1.68 (1.60; 1.75)), and breast cancer (1.08 (1.05; 1.11))) and overall cancer (1.03 (1.02; 1.04)). All these associations were linear except for breast cancer in postmenopausal women. Similar results were observed when other markers of central and overall adiposity were used. For mortality, nine cancer sites were linearly associated with BMI and eight with waist circumference and body fat percentage.Conclusion: Adiposity, regardless of the marker used, was associated with an increased risk in 10 cancer sites. [ABSTRACT FROM AUTHOR]

Gallbladder cancer is rare but associated with significant morbidity and mortality necessitating the early identification of premalignant and malignant lesions to improve overall prognosis. Despite limited evidence regarding the effectiveness of transabdominal ultrasound (US) in the detection of gallbladder polyps, it plays a key role in current European guidelines. The aim of this study was to investigate gallbladder polyp prevalence in a western European population and assess the diagnostic accuracy of transabdominal US. Data from patients who underwent cholecystectomy for US detected gallbladder polypoid lesions at four hospitals in Ireland and the United Kingdom between 2010 and 2018 were retrospectively collected. Patient demographics, ultrasonographic, and histopathologic findings were analyzed. A total of 134 patients underwent cholecystectomy for US-detected gallbladder polyps. After histopathologic examination, pseudopolyps were found in 75 (56%) specimens with dysplastic or malignant polyps seen in only six (4.5%) specimens. Mean size for neoplastic polyps was 33 mm. The positive predictive value for US in detecting neoplastic polyps in this study was 4.5%, which is significantly lower than the 10%-15% reported previously. Although the prevalence of neoplastic polyps in this study is higher than in the previous literature, the distribution of pseudopolyps and true polyps is as expected. With all malignant polyps being >10 mm in diameter, these findings support the current size thresholds stated in European guidelines. The poor diagnostic accuracy of US demonstrated may have led to significant number of patients undergoing unnecessary surgical intervention, further supporting the argument for improved strategies for the investigation of gallbladder polyps. [ABSTRACT FROM AUTHOR]

Objectives: To identify MRI features that are helpful for the differentiation of gallbladder neuroendocrine tumors (GB-NETs) from gallbladder adenocarcinomas (GB-ADCs) and to evaluate their prognostic values.Methods: Between January 2008 and December 2018, we retrospectively enrolled patients who underwent MRI for GB malignancy. Two radiologists independently assessed the MRI findings and reached a consensus. Significant MRI features, which distinguish GB-NETs from GB-ADCs, were identified. Cox regression analyses were performed to find MRI features that were prognostic for overall survival.Results: There were 63 patients with GB-NETs (n = 21) and GB-ADCs (n = 42). Compared with GB-ADCs, GB-NETs more frequently demonstrated the following MRI features: well-defined margins, intact overlying mucosa, and thick rim contrast enhancement and/or diffusion restriction (ps < 0.001). Liver metastases were more common and demonstrated thick rim contrast enhancement and diffusion restriction in GB-NETs (ps < 0.001). Lymph node (LN) metastasis showed thick rim diffusion restriction more often in GB-NETs than in GB-ADCs (p = 0.009). On quantitative analysis, the sizes of the GB mass and metastatic LNs in GB-NETs were larger than those in GB-ADCs (p = 0.002 and p = 0.010, respectively). The ratio of apparent diffusion coefficient values between the lesion and the spleen was lower in the GB mass, liver metastases, and LN metastases of GB-NETs than those of GB-ADCs (p < 0.001, p = 0.017, and p < 0.001, respectively). Survival analysis revealed that a large metastatic LN (hazard ratio 1.737; 95% confidence interval, 1.112-2.712) was the only poor prognostic factor (p = 0.015).Conclusion: Several MRI features aided in differentiating between GB-NETs and GB-ADCs. A large metastatic LN was associated with poor survival.Key Points: • Compared with gallbladder adenocarcinomas (GB-ADCs), neuroendocrine tumors (GB-NETs) and their metastases to the liver and lymph nodes more frequently demonstrated a thick rim appearance on contrast-enhanced MRI and diffusion-weighted images. • The ratio of apparent diffusion coefficient values between the lesion and the spleen was significantly lower for the primary mass, liver metastases, and lymph node metastases of GB-NETs than for those of GB-ADCs. • A large metastatic lymph node was the only poor prognostic factor for overall survival in patients with GB-NETs and GB-ADCs. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the clinicopathological features and prognosis of gallbladder neuroendocrine carcinoma (GB-NEC). Patients and Methods: Fifteen patients with GB-NEC and 171 patients with gallbladder adenocarcinoma (GB-ADC) treated in two tertiary medical centers between 2009 and 2015 were included. The clinicopathological features and prognostic risk factors of GB-NEC were analyzed retrospectively. A propensity score matching in a 1:2 ratio was used to compare the prognosis of GB-NEC and GB-ADC. Results: For patients with GB-NEC, the median age of patients was 58.4 years (range 26– 75), with a M:F ratio of 7:8. Based on 2010 WHO classification, ten cases were pathologically confirmed as NECs and five cases as MANECs. For TNM staging, eleven patients were stage III or above; while for Nevin staging, seven patients were stage IV or above. The 1-, 2-, and  3-year overall survival (OS) of GB-NEC were 60.0%, 38.8% and 31.1%, respectively, and the median survival time was 20.4 months. Patients with lymph node metastasis had significantly shorter survival than those without (OS: 10.4 vs 26.0 months, p< 0.05). Accordingly, patients of Nevin stage III had better OS than those of Nevin stage IV (p< 0.05), but other potential risk factors including gender, age, clinical symptoms, TNM stage, histopathologic subtype and treatment showed no significance. After the propensity score matching, the baseline variables had no significant difference between 15 patients with GB-NEC and 30 patients with GB-ADC, survival analysis showed GB-NEC had worse prognosis (3-year overall survival rate: 31.1% vs 63.8%, p< 0.01). Conclusion: Nevin staging helps classify patients of GB-NEC with different prognosis and the lymph node metastasis is a strong negative prognostic factor for OS. The propensity score analysis revealed even with the similar stage and treatment, GB-NEC still had worse OS than GB-ADC. [ABSTRACT FROM AUTHOR]

Primary hepatobiliary cancer incidence in the UK is rising and survival rates are low. Surgery is the main curative option for these cancers, but multimodality therapies are expanding. The aim of our original study was to determine trends in survival, over an 8-year period, of patients treated for primary hepatobiliary cancers at our tertiary referral Centre. Patients treated for the most common types of primary hepatobiliary cancers, namely Hepatocellular carcinoma (HCC), Cholangiocarcinoma and Gallbladder cancer between January 2009 and December 2016 were retrospectively analysed from a prospective database linked to UK Hospital Episode Statistics data. A total of 1536 patients with primary hepatobiliary cancers were assessed and treatment plans formulated at our supra-regional specialist Hepatobiliary MDT. The primary hepatobiliary cancers treated were HCC (n = 836), Cholangiocarcinoma (n = 516), and Gallbladder cancer (n = 184). Survival for all the 3 cancers was significantly better with curative treatment. Overall median survival times were 350, 180, and 150 days respectively for HCC, Cholangiocarcinoma and Gallbladder cancer. Excluding best supportive care patients, the respective survival figures were 900, 600, and 400 days. Survival for HCC patients improved over time and was significantly increased in the final 3 years of the study (p ≤ 0.011 for all). Cholangiocarcinoma and Gallbladder cancer survivals were poor and did not change significantly over time. HCC outcome has improved in association with expanded multimodal therapies. Survivals for cholangiocarcinoma and gallbladder cancer remain poor in parallel with limited expansion of multimodal therapies highlighting an unmet therapeutic need for biliary tract cancers. [ABSTRACT FROM AUTHOR]

Background: Despite improvements in multidisciplinary management, patients with biliary tract cancer have a poor outcome. Only 20% of patients are eligible for surgical resection with curative intent, with 5-year overall survival of less than 10% for all patients. To our knowledge, no studies have described a benefit of adjuvant therapy. We aimed to determine whether adjuvant capecitabine improved overall survival compared with observation following surgery for biliary tract cancer.Methods: This randomised, controlled, multicentre, phase 3 study was done across 44 specialist hepatopancreatobiliary centres in the UK. Eligible patients were aged 18 years or older and had histologically confirmed cholangiocarcinoma or muscle-invasive gallbladder cancer who had undergone a macroscopically complete resection (which includes liver resection, pancreatic resection, or, less commonly, both) with curative intent, and an Eastern Cooperative Oncology Group performance status of less than 2. Patients who had not completely recovered from previous surgery or who had previous chemotherapy or radiotherapy for biliary tract cancer were also excluded. Patients were randomly assigned 1:1 to receive oral capecitabine (1250 mg/m2 twice daily on days 1-14 of a 21-day cycle, for eight cycles) or observation commencing within 16 weeks of surgery. Treatment was not masked, and allocation concealment was achieved with a computerised minimisation algorithm that stratified patients by surgical centre, site of disease, resection status, and performance status. The primary outcome was overall survival. As prespecified, analyses were done by intention to treat and per protocol. This study is registered with EudraCT, number 2005-003318-13.Findings: Between March 15, 2006, and Dec 4, 2014, 447 patients were enrolled; 223 patients with biliary tract cancer resected with curative intent were randomly assigned to the capecitabine group and 224 to the observation group. The data cutoff for this analysis was March 6, 2017. The median follow-up for all patients was 60 months (IQR 37-60). In the intention-to-treat analysis, median overall survival was 51·1 months (95% CI 34·6-59·1) in the capecitabine group compared with 36·4 months (29·7-44·5) in the observation group (adjusted hazard ratio [HR] 0·81, 95% CI 0·63-1·04; p=0·097). In a protocol-specified sensitivity analysis, adjusting for minimisation factors and nodal status, grade, and gender, the overall survival HR was 0·71 (95% CI 0·55-0·92; p=0·010). In the prespecified per-protocol analysis (210 patients in the capecitabine group and 220 in the observation group), median overall survival was 53 months (95% CI 40 to not reached) in the capecitabine group and 36 months (30-44) in the observation group (adjusted HR 0·75, 95% CI 0·58-0·97; p=0·028). In the intention-to-treat analysis, median recurrence-free survival was 24·4 months (95% CI 18·6-35·9) in the capecitabine group and 17·5 months (12·0-23·8) in the observation group. In the per-protocol analysis, median recurrence-free survival was 25·9 months (95% CI 19·8-46·3) in the capecitabine group and 17·4 months (12·0-23·7) in the observation group. Adverse events were measured in the capecitabine group only, and of the 213 patients who received at least one cycle, 94 (44%) had at least one grade 3 toxicity, the most frequent of which were hand-foot syndrome in 43 (20%) patients, diarrhoea in 16 (8%) patients, and fatigue in 16 (8%) patients. One (<1%) patient had grade 4 cardiac ischaemia or infarction. Serious adverse events were observed in 47 (21%) of 223 patients in the capecitabine group and 22 (10%) of 224 patients in the observation group. No deaths were deemed to be treatment related.Interpretation: Although this study did not meet its primary endpoint of improving overall survival in the intention-to-treat population, the prespecified sensitivity and per-protocol analyses suggest that capecitabine can improve overall survival in patients with resected biliary tract cancer when used as adjuvant chemotherapy following surgery and could be considered as standard of care. Furthermore, the safety profile is manageable, supporting the use of capecitabine in this setting.Funding: Cancer Research UK and Roche. [ABSTRACT FROM AUTHOR]

Background: We assessed the activity of gemcitabine (G) and cisplatin/gemcitabine (C/G) in patients with locally advanced (LA) or metastatic (M) (advanced) biliary cancers (ABC) for whom there is no standard chemotherapy.Methods: Patients, aged > or =18 years, with pathologically confirmed ABC, Karnofsky performance (KP) > or =60, and adequate haematological, hepatic and renal function were randomised to G 1000 mg m(-2) on D1, 8, 15 q28d (Arm A) or C 25 mg m(-2) followed by G 1000 mg m(-2) D1, 8 q21d (Arm B) for up to 6 months or disease progression.Results: In total, 86 patients (A/B, n=44/42) were randomised between February 2002 and May 2004. Median age (64/62.5 years), KP, primary tumour site, earlier surgery, indwelling biliary stent and disease stage (LA: 25/38%) are comparable between treatment arms. Grade 3-4 toxicity included (A/B, % patients) anaemia (4.5/2.4), leukopenia (6.8/4.8), neutropenia (13.6/14.3), thrombocytopenia (9.1/11.9), lethargy (9.1/28.6), nausea/vomiting (0/7.1) and anorexia (2.3/4.8). Responses (WHO criteria, % of evaluable patients: A n=31 vs B n=36): no CRs; PR 22.6 vs 27.8%; SD 35.5 vs 47.1% for a tumour control rate (CR+PR+SD) of 58.0 vs 75.0%. The median TTP and 6-month progression-free survival (PFS) (the primary end point) were greater in the C/G arm (4.0 vs 8.0 months and 45.5 vs 57.1% in arms A and B, respectively).Conclusion: Both regimens seem active in ABC. C/G is associated with an improved tumour control rate, TTP and 6-month PFS. The study has been extended (ABC-02 study) and powered to determine the effect on overall survival and the quality of life. [ABSTRACT FROM AUTHOR]

Introduction Unsuspected Gall bladder carcinoma (UGBC) is erroneously leveled as incidental carcinoma gallbladder. An attempted radical surgery later is not possible in sizable number of cases as the tumor is either disseminated or locally unresectable at laparotomy. Purpose of this report was to study the preoperative imaging and to predict the presence of residual disease from retrospective analysis of prospectively maintained database. Materials and Methods The study comprises of retrospective analysis of 16 patients of UGBC out of 84 patients of Gallbladder carcinoma (GBC) admitted from 2011 to 2016. Ultrasound (USG) abdomen and intraoperative findings prior to initial cholecystectomy were studied. The clinical evaluation and CECT± FDGPET scan was performed in all as a protocol to stage the tumor prior to definitive surgery. Resectable patients were subjected to laparotomy. Results Laparoscopic cholecystectomy was performed in 7, open in 6 and in three patients; laparoscopy was converted to open cholecystectomy. All but one patient were operated outside. The median time from cholecystectomy to attempted radical surgery was 7 weeks (5 days-4.5 months). All patients were referred with histopathological report for further surgery, out of these 6 had persistent pain, 2 had postoperative jaundice and 4 patients had severe anorexia and weight loss. 81.25% (13/16) patients presented with their ultrasound report prior to cholecystectomy. 43.75% patients (7/16) had features of uncomplicated cholelithiasis (normal gallbladder wall thickness, single or multiple stones or mucocele) and suspicious clinical features of malignancy were reported in 56.25% (9/16) cases prior to cholecystectomy. On staging CT, 68.75% (11/16) had gall bladder wall thickening (asymmetrical=6) with or without associated periportal lymphnodes and loss of interphase with adjoining liver. 85.71% (6/7) patients with uncomplicated cholelithiasis reported on preoperative U/S underwent R0 resections and 4 of them had no evidence of residual diseases in resected specimen while remaining 3 patients had e/o resectable residual or recurrent GB mass. Surgery could not be contemplated in 1 patient due to locally unresectable disease. 44.45% (4/9) patients with suspicious U/S findings underwent R0 resections. All of them had residual/ recurrent diseases without or with GB fossa mass. The remaining 5 patients (55.55%), could not undergo surgery (distant metastasis=3, locally unresectable disease=2) Conclusions: The incidental GBC masquerading as uncomplicated cholelithiasis on U/S can later develop GB mass in 42.8% cases (3/7). The incidence of finding GB mass increases to 100% (8/15) in presence of suspicious lesions on U/S. Intra operative frozen calot's triangle, duodenal adhesions and thickened GB wall should raise the suspicion of tumor. The study reinforces alertness and calls for high index of suspicion of GBC on U/S in patients undergoing cholecystectomy in endemic region and recommends further investigations in cases of suspicious lesions on U/S prior to cholecystectomy. [ABSTRACT FROM AUTHOR]