Gallbladder cancer: epidemiology and outcome
Gallbladder cancer, though generally considered rare, is the most common malignancy of the biliary tract, accounting for 80%–95% of biliary tract cancers. An early diagnosis is essential as this malignancy progresses silently with a late diagnosis, often proving fatal. Its carcinogenesis follows a progression through a metaplasia–dysplasia–carcinoma sequence. This comprehensive review focuses on and explores the risks, management, and outcomes for primary gallbladder carcinoma. Epidemiological studies have identified striking geographic and ethnic disparities – inordinately high occurrence in American Indians, elevated in Southeast Asia, yet quite low elsewhere in the Americas and the world. Age, female sex, congenital biliary tract anomalies, and a genetic predisposition represent important risk factors that are immutable. Environmental triggers play a critical role in eliciting cancer developing in the gallbladder, best exemplified by cholelithiasis and chronic inflammation from biliary tract and parasitic infections. Mortality rates closely follow incidence; those countries with the highest prevalence of gallstones experience the greatest mortality from gallbladder cancer. Vague symptoms often delay the diagnosis of gallbladder cancer, contributing to its overall progression and poor outcome. Surgery represents the only potential for cure. Some individuals are fortunate to be incidentally found to have gallbladder cancer at the time of cholecystectomy being performed for cholelithiasis. Such an early diagnosis is imperative as a late presentation connotes advanced staging, nodal involvement, and possible recurrence following attempted resection. Overall mean survival is a mere 6 months, while 5-year survival rate is only 5%. The dismal prognosis, in part, relates to the gallbladder lacking a serosal layer adjacent to the liver, enabling hepatic invasion and metastatic progression. Improved imaging modalities are helping to diagnose patients at an earlier stage. The last decade has witnessed improved outcomes as aggressive surgical management and preoperative adjuvant therapy has helped prolong survival in patients with gallbladder cancer. In the future, the development of potential diagnostic markers for disease will yield screening opportunities for those at risk either with ethnic susceptibility or known anatomic anomalies of the biliary tract. Meanwhile, clarification of the value of prophylactic cholecystectomy should provide an opportunity for secondary prevention. Primary prevention will arrive once the predictive biomarkers and environmental risk factors are more clearly identified.
Gallbladder cancer (GC) is a relatively rare but highly lethal neoplasm. We review the epidemiology, etiology, pathology, symptoms, diagnosis, staging, treatment, and prognosis of GC.
A Pubmed database search between 1971 and February 2007 was performed. All abstracts were reviewed and articles with GC obtained; further references were extracted by hand-searching the bibliography. The database search was done in the English language.
The accurate etiology of GC remains unclear, while the symptoms associated with primary GC are not specific. Treatment with radical cholecystectomy is curative but possible in only 10% to 30% of patients. For patients whose cancer is an incidental finding on pathologic review, re-resection is indicated, where feasible, for all disease except T1a. Patients with advanced disease should receive palliative treatment. Laparoscopic cholecystectomy is contraindicated in the presence of GC.
Prognosis generally is extremely poor. Improvements in the outcome of surgical resection have caused this approach to be re-evaluated, while the role of chemotherapy and radiotherapy remains controversial.
Gallbladder cancer worldwide: Geographical distribution and risk factors
Gallbladder cancer is a relatively rare neoplasm that shows, however, high incidence rates in certain world populations. The interplay of genetic susceptibility, lifestyle factors and infections in gallbladder carcinogenesis is still poorly understood. Age-adjusted rates were calculated by cancer registry-based data. Epidemiological studies on gallbladder cancer were selected through searches of literature, and relative risks were abstracted for major risk factors. The highest gallbladder cancer incidence rates worldwide were reported for women in Delhi, India (21.5/100,000), South Karachi, Pakistan (13.8/100,000) and Quito, Ecuador (12.9/100,000). High incidence was found in Korea and Japan and some central and eastern European countries. Female-to-male incidence ratios were generally around 3, but ranged from 1 in Far East Asia to over 5 in Spain and Colombia. History of gallstones was the strongest risk factor for gallbladder cancer, with a pooled relative risk (RR) of 4.9 [95% confidence interval (CI): 3.3–7.4]. Consistent associations were also present with obesity, multiparity and chronic infections like Salmonella typhi and S. paratyphi [pooled RR 4.8 (95% CI: 1.4–17.3)] and Helicobacter bilis and H. pylori [pooled RR 4.3 (95% CI: 2.1–8.8)]. Differences in incidence ratios point to variations in gallbladder cancer aetiology in different populations. Diagnosis of gallstones and removal of gallbladder currently represent the keystone to gallbladder cancer prevention, but interventions able to prevent obesity, cholecystitis and gallstone formation should be assessed.
Gemcitabine and Carboplatin in Inoperable, Loco-Regionally Advanced and Metastatic Gallbladder Cancer- A Study from Northern Indian Cancer Institute
Aims: The primary objective of this study was to determine the response rates of the gemcitabine and carboplatin combination chemotherapy in treatment naïve patients with inoperable gall bladder cancer. The secondary objectives were to evaluate the toxicity, progression free survival (PFS), and overall survival (OS).
Methodology: Treatment naïve patients with histologically proven inoperable gall bladder cancer treated with gemcitabine and carboplatin chemotherapy between February 2011 and December 2014 were included in this study. The dose of gemcitabine was 1 gm/m2 on day 1 and 8, and carboplatin [target AUC (area under the concentration versus time curve in mg/ml) of 5] on day 1, in a 21 day cycle. CT scan was used for response assessment.
Results: There were 32 men and 92 women with a median age of 59 years (range 26-75 years). Of the 124 patients, 9 (7.3%) patients achieved a complete response and 54 (43.5%) patients achieved a partial response for an overall response rate of 50.8%. The median PFS was 4.6 months [95% confidence interval (CI) 4–5.5 months], with 1-year survival rate of 20.2%. Common toxicity criteria (CTC) grade 3 anaemia was seen in 6 (4.8%) patients. Grade 3 and 4 neutropenia was observed in 11 (8.9%) and 4 (3.2%) patients respectively, whereas 9 (7.3%) patients experienced Grade 3 thrombocytopenia.
Conclusion: The combination of gemcitabine and carboplatin is active in advanced gall bladder carcinoma with mild toxicity.
Squamous Cell Carcinoma of Gallbladder – An Uncommon Presentation
A 51-year-old male patient presented with pain in the upper right quadrant of abdomen since two months, associated with weight loss and fever. Contrast enhanced computed tomography abdomen revealed gallbladder with wall thickening which was asymmetric and heterogeneous at junction of body. An initial diagnosis of cholecystitis with element of cholangitis and abnormal wall thickening with multiple tiny calculi was considered. Open radical cholecystectomy was done. Microscopic and immunohistochemical findings established the diagnosis of moderately differentiated squamous cell carcinoma of the gallbladder. Adjuvant chemotherapy regimen consisting of paclitaxel 175 mg/m2 and carboplatin AUC 6 was given three weekly for six cycles in the present case. Six months after treatment completion, patient is on regular follow up and disease free on clinical and radiological examination.
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 Gourgiotis, S., Kocher, H.M., Solaini, L., Yarollahi, A., Tsiambas, E. and Salemis, N.S., 2008. Gallbladder cancer. The American Journal of Surgery, 196(2), pp.252-264.
 Randi, G., Franceschi, S. and La Vecchia, C., 2006. Gallbladder cancer worldwide: geographical distribution and risk factors. International journal of cancer, 118(7), pp.1591-1602.
 Talwar, V., Raina, S., Goel, V. and Doval, D.C., 2017. Gemcitabine and carboplatin in inoperable, loco-regionally advanced and metastatic gallbladder cancer-A study from Northern Indian Cancer Institute. Journal of Advances in Medicine and Medical Research, pp.1-7.
 Gupta, V., Kaur, P., Khurana, A., Chauhan, A.K. and Parmar, P., 2016. Squamous Cell Carcinoma of Gallbladder–An Uncommon Presentation. International Journal of TROPICAL DISEASE & Health, pp.1-4.