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

Gallbladder carcinoma is an uncommon but highly malignant tumor with a poor 5-year survival rate. The presence of gallstones is a well-established ris k factor for gallbladder carcinoma, and the risk seems to correlate with st one size. Metaplastic changes of the gallbladder epithelium present in chro nic cholecystitis may be a premalignant lesion. Solitary polyps with a size of greater than 1 cm are recognized as a predisposing factor for gallbladd er carcinoma when their characteristics are echopenic. sessile, and high ce ll density. Endoscopic ultrasound is the most useful technique to detect th e early changes of malignancy in polyps. Anomalous junction of pancreaticob iliary ducts (AJPBD) without a choledochal cyst and porcelain gallbladder i s an additional risk factor for gallbladder malignancy. At the molecular le vel, 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 gal lbladder carcinoma in patients with AJPBD is that chronic reflux of pancrea tic juice causes intestinal metaplasia, hyperplasia, and dysplasia with the mutation of p53 and K-ras. In contrast, the causal relationship between po rcelain gallbladder and malignancy is yet to be established. In this articl e, recognition of risk factors for gallbladder carcinoma was summarized wit h special attention to gallstones and chronic inflammation.