Carcinogenesis of malignant lesions of the gall bladder. The impact of chronic inflammation and gallstones

Abstract

Gallbladder carcinoma is an uncommon but highly malignant tumor with a poor 5-year survival rate. The presence of gallstones is a well-established risk factor for gallbladder carcinoma, and the risk seems to correlate with stone size. Metaplastic changes of the gallbladder epithelium present in chronic cholecystitis may be a premalignant lesion. Solitary polyps with a size of greater than 1 cm are recognized as a predisposing factor for gallbladder carcinoma when their characteristics are echopenic, sessile, and high cell density. Endoscopic ultrasound is the most useful technique to detect the early changes of malignancy in polyps. Anomalous junction of pancreaticobiliary ducts (AJPBD) without a choledochal cyst and porcelain gallbladder is an additional risk factor for gallbladder malignancy. At the molecular level, it has been proposed that chronic inflammation of the gallbladder may lead to the loss of p53 gene heterozygosity and excessive expression of p53 protein. Furthermore, a proposed mechanism underlying the high risk of gallbladder carcinoma in patients with AJPBD is that chronic reflux of pancreatic juice causes intestinal metaplasia, hyperplasia, and dysplasia with the mutation of p53 and K-ras. In contrast, the causal relationship between porcelain gallbladder and malignancy is yet to be established. In this article, recognition of risk factors for gallbladder carcinoma was summarized with special attention to gallstones and chronic inflammation.