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Gallbladder Cancer Gallbladder Cancer—Current Management Options Aslam Ejaz, MD, 1 Teviah Sachs, MD, MPH, 2 Ihab R Kamel, MD, PhD 3 and Timothy M Pawlik, MD, MPH, PhD 4 1. Research Fellow in Surgical Oncology, Division of Surgical Oncology, Department of Surgery; 2. Clinical Fellow in Surgical Oncology, Division of Surgical Oncology, Department of Surgery; 3. Professor of Radiology, Department of Radiology; 4. Chief, Division of Surgical Oncology; Professor of Surgery and Oncology; John L Cameron Professor of Alimentary Tract Surgery, Department of Surgery, Johns Hopkins Hospital, Baltimore, Maryland, US Abstract Carcinoma of the gallbladder is an aggressive disease, often with a poor prognosis. Although the incidence has remained relatively stable over the past decade, an increase in laparoscopic cholecystectomy has resulted in a increase in cases detected at earlier stages offering an opportunity for better prognosis. Diagnostic techniques including ultrasound (US), endoscopic US (EUS), computed tomography (CT) with multiplanar reconstruction, magnetic resonance imaging (MRI), positron emission tomography (PET), and diagnostic laparoscopy have evolved. Surgical resection to negative microscopic margins with lymphadenectomy offers the only chance for long-term survival. Adjuvant chemotherapy and radiation may be indicated in a subset of patients, and data have suggested a beneficial effect on overall survival. A multidisciplinary approach is required for the optimal management of this complex disease. Keywords Gallbladder cancer, biliary tract cancer Disclosure: The authors have no conflicts of interest to declare. Received: July 24, 2013 Accepted: August 20, 2013 Citation: Oncology & Hematology Review (US), 2013;9(2):102–8 Correspondence: Timothy M Pawlik, MD, MPH, PhD, Chief, Division of Surgical Oncology, Professor of Surgery and Oncology, John L Cameron Professor of Alimentary Tract Surgery, Department of Surgery, Blalock 688, 600 N Wolfe Street, Baltimore, MD 21287, US. E: In 1777, Maximilian de Stoll, a Viennese surgeon published the first credited description of gallbladder cancer. Over two centuries later, gallbladder cancer remains a difficult disease with a dismal prognosis for those patients with advanced disease. Historically described as an extrahepatic biliary cancer, gallbladder cancer is now regarded as a distinct disease from other biliary cancers. Despite its relative infrequency, it is the most common cancer of the biliary system. With the advent of laparoscopic cholecystectomy the incidence of early-stage gallbladder cancer has increased, though it is not uncommon for gallbladder cancer to present as advanced disease. As such, it is a challenge for patients and clinicians alike. Here we review the epidemiology, diagnostic techniques, surgical management, adjuvant therapy, and future clinical targets for gallbladder cancer. Incidence/Epidemiology Gallbladder cancer is the fifth most common gastrointestinal malignancy in the US and the most common cancer of the biliary system. 1 It has an incidence of approximately one to two per 100,000 people, with approximately five to six thousand new cases per year, as estimated by the Surveillance, Epidemiology and End Results (SEER) database. While showing a small decrease in overall incidence over the past 10 years, the incidence in younger populations is growing. Socioeconomic status and access to cholecystectomy have been shown to relate to the incidence gallbladder cancer. 2 Its incidence is higher in South American countries, especially Chile, and in populations where cholelithiasis is prevalent. 3,4 The incidence 102 of gallbladder cancer is increasing in China and other countries where westernization of diet and increasing obesity are thought to play a role. 5,6 Between 10 and 15 % of the adult US population is affected by cholelithiasis— the number one risk factor for all biliary cancers—and over 750,000 cholecystectomies are performed annually in the US. 7 This has led to an increase in incidentally detected gallbladder cancers, of which approximately 80 % are stage I or II. 8 It has been estimated that gallbladder cancer found incidentally after cholecystectomy occurs in 0.2–2.9 % of cases, representing anywhere from 40 to 70 % of all gallbladder cancer diagnoses. 9,10 Demographics A number of demographic variables play a role in gallbladder cancer. Females have a 40 to 60  % higher incidence of gallbladder cancer than men. 7 Race and ethnicity also play a role, with incidence highest in Caucasian Hispanics and Native Americans, and lowest in non-Hispanic Caucasians and African Americans. The incidence of gallbladder cancer also increases with age, with mean diagnosis in the seventh decade of life. 11 Risk Factors Chronic inflammation of the gallbladder is the most identifiable cause for development of gallbladder cancer. 3 While this is most often due to cholelithiasis, any disease process that causes chronic inflammation of the gallbladder will increase the risk for gallbladder cancer. While other extrahepatic biliary cancers are associated with pigmented stones, © Tou c h M E d ica l ME d ia 2013