Gallbladder cancer: a morphological and molecular update

Abstract

Gallbladder cancer (GBC) shows a marked geographical variation in its incidence, with the highest figures being seen in India and Chile and relatively low levels in many Western countries. Risk factors for its development include the presence of gallstones, infection and the presence of an anomalous pancreatobiliary ductal junction. It can arise from either a pathway involving metaplasia or dysplasia or one in which there is a pre-existing adenoma. The former is the more common and, because it is often not associated with a macroscopically recognizable lesion, leads to the recommendation that all gallbladders need to be examined microscopically. Accurate staging of invasive cancers is essential to determine prognosis and treatment, and this requires extensive tumour sampling. A number of genetic alterations have been identified in the preinvasive and invasive stages of GBC and they support the morphological evidence of there being two pathways by which tumours develop. Some of these genetic changes are associated with particular risk factors. For example, cases with anomalous pancreatobiliary ductal junction show a higher frequency of K-ras mutations. Some changes are associated with differences in prognosis. For example, cancers without expression of p21 but with expression for p27 have a better prognosis, whereas those that express c-erb-B2 have a worse one. Work has also been done on identifying clinical, imaging and other factors that indicate that patients have a higher risk of having GBC. This is particularly important in high-incidence areas in which GBC is a significant public health problem.

Hepatopancreatoduodenectomy-Lesson’s with 35 Patients over 10 Years

“…1,15,19,22,24 In the western hemisphere, very few groups are interested in reproducing this experience. So far, only Hemming et al 15 published a consisted report with HPD in the western countries.…”

“…22 Thus, due to the rich submucosal network of the infundibulum region, the tumors of this region are generally more aggressive, frequently present with advanced lymph node disease, hepatoduodenal ligament involvement and may mimic a hilar PseudoKlatskin cholangiocarcinoma. Tumors at the bottom of the gallbladder are more likely to be resected and their treatment should invariably comprise hepatic resection.…”

Seek and ye shall find: the importance of careful macroscopic examination and thorough sampling in 2522 cholecystectomy specimens

“…The two main morphological pathways to gallbladder carcinoma are through metaplasia and dysplasia in flat mucosa (the more common scenario), or arising within a macroscopically visible adenoma. There are certain differences at a molecular level between the pathways [6].…”

A genome-wide association study identifies SNP in DCC is associated with gallbladder cancer in the Japanese population

“…Only few somatic genetic changes including mutations in K-ras, TP53 and p16 Ink4 /CDKN2 as well as loss of heterozygosity at several chromosomal regions harboring known or putative tumor-suppressor genes have been reported in GCs. 5,7 Hence, identification of novel genetic factors associated with susceptibility to GC should provide new insights into pathogenesis and novel therapeutic interventions of GC. Here, we report a genome-wide association study (GWAS) that aims to identify genetic factors associated with GC susceptibility.…”

“…Only few somatic genetic changes including mutations in K-ras, TP53 and p16 Ink4 /CDKN2 as well as loss of heterozygosity at several chromosomal regions harboring known or putative tumor-suppressor genes have been reported in GCs. 5,7 Hence, identification of novel genetic factors associated with susceptibility to GC should …”