Gallbladder Cancer: The Recent Progress

Dear Colleagues, 

Gallbladder cancer (GBC) is an aggressive malignancy of the biliary tract and is associated with a poor prognosis (~10% overall 5-year survival). Therefore, early detecting GBC in its initial stage offers patients their best chance of cure, but identification of high-risk patients and appropriate surveillance methods are still controversial.

Worldwide occurrence of GBC is <2/100,000 and rates of incidental diagnosis of laparoscopic cholecystectomy range from 0.28 to 2.10%. GBC predominantly affects elderly patients, mean age being 65 years, and females were more often affected, GBC shows a marked geographical variation in its incidence, with the highest incidences being observed in Chile, India, Pakistan, and Ecuador, while relatively low incidence is noted in many Western countries, except for Latin American and Native American individuals. Low, but still increased risk is seen in Eastern Europe, Israel, and Japan.

Most important risk factor for GBC is chronic cholecystitis, with cholelithiasis: >80% of GBC are associated with gallstone and porcelain gallbladder increases risk. Other risk factors include infections with liver flukes and Salmonella spp., primary sclerosing cholangitis, anatomic anomalies of biliary tree, and gastrointestinal polyposis syndrome.

Multiple histopathologic subtypes of GBC are recognized by the WHO: biliary type is most the common morphology with variants, including mucinous adenocarcinoma, clear cell carcinoma, poorly cohesive carcinoma with or without signet-ring cells, adenosquamous and squamous cell carcinoma, and intestinal-type adenocarcinoma. Common molecular alterations of GBC are mutations (CDKN2A, CDKN2B, ARID1A, PIK3CA, TP53, K-RAS), amplification (ERBB2), microsatellite instability, and promoter methylation of CDKN2A.

GBC can arise from either a pathway involving metaplasia or dysplasia or one in which there is a pre-existing adenoma. In addition, number of genetic alterations have been identified in the pre-invasive and invasive stages of GBC. However, exact carcinogenesis/pathogenesis of GBC remains unknown.

Surgical treatment is the most certain method for the radical cure of GBC, and accurate staging of invasive GBC is essential to determine prognosis and treatment. In addition, chemotherapy, molecular targeted therapy, and radiotherapy are also important for the patients who are difficult to cure with surgery. Moreover, pathological diagnosis using EUS-guided tissue acquisition (EUS-TA) is sometimes needed, and specimens surgically resected or obtained by EUS-TA are also used for genome profiling. Gene therapies are currently spreading, as well as conventional chemotherapy and radiotherapy in the patients with unresectable and recurrence cases, and therefore molecular/genetic diagnosis of entire specimens of GBC is important.

This Special Issue, entitled "Gallbladder Cancer: The Recent Progress", welcomes the latest articles about GBC pathogenesis, gene genetics, diagnosis, surgical treatment, chemotherapy, radiotherapy, and endotherapy, including comprehensive review articles regarding update of GBC. We also welcome the contribution of the challenging works on the subjects listed in the Keywords.

Dr. Keisuke Iwata
Prof. Dr. Takuji Tanaka
Guest Editors

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• gallbladder cancer
• epidemiology
• geographic distribution
• pathogenesis
• molecular pathology
• precursor lesion
• risk factor
• early detection
• incidental gallbladder cancer
• surveillance for high-risk group
• imaging diagnosis
• EUS-TA
• chemotherapy
• radiotherapy
• surgical treatment
• robotic surgery
• neoadjuvant therapy
• genome profiling
• liquid biopsy
• therapy
• biomarkers
• targeting molecular therapy
• biliary drainage