Histopathology and Staging

Gallbladder cancers are aggressive tumors with a propensity for local invasion, lymphatic metastasis, and peritoneal dissemination. The overwhelming majority of these neoplasms are adenocarcinomas. Papillary subtype has been associated with a relatively better prognosis compared to mucinous and adenosquamous subtypes (132). The AJCC staging is based on the familiar TMN system. T stage is dependent on the depth of invasion relative to the gallbladder wall and adjacent organs. The wall of the gallbladder consists of a mucosa and lamina propria, a thin muscular layer, perimuscular connective tissue, and a serosa. However, it should be noted that the gallbladder wall lacks a serosal covering along its border with the liver and the perimuscular connective tissue is continuous with the liver connective tissue. T1 tumors are confined to the mucosa. T2 tumors have invaded up to but not through the serosa. T3 tumors have penetrated the serosa and directly invaded an adjacent organ. This most likely involves local invasion into the liver and is limited to <2 cm in extent. T4 tumors are those that invade >2 cm into the liver or involve two or more adjacent organs via direct extension. The T-staging of gallbladder cancers is particularly important in postcholecystectomy patients, since depth of invasion dictates treatment recommendations and outcome. In considering N stage, at least three nodes must be evaluable to be considered adequate nodal staging. Nodal disease is classified as N0 for the absence of tumor within at least three resected lymph nodes. N1 disease is assigned to any positive cystic duct node or hepatoduodenal ligament nodes. N2 disease includes malignancy within celiac, superior mesenteric, or peripancreatic nodes. Metastatic

FIGURE 6 Axial CT images of a porcelain gallbladder. Note the marked, circumferential calcification of the gallbladder wall (A) and the intrahepatic biliary ductal dilatation (B). This patient had a gallbladder cancer arising in the setting of a porcelain gallbladder, which had progressed to involve the common hepatic duct. Abbreviation: CT, computed tomography.

FIGURE 6 Axial CT images of a porcelain gallbladder. Note the marked, circumferential calcification of the gallbladder wall (A) and the intrahepatic biliary ductal dilatation (B). This patient had a gallbladder cancer arising in the setting of a porcelain gallbladder, which had progressed to involve the common hepatic duct. Abbreviation: CT, computed tomography.

disease refers to distant metastasis. It should be noted that most of the studies cited in this chapter refer to the TMN staging as outlined in the fifth edition system. These staging systems are designed to have the widest applicability in the multimodality treatment of gallbladder cancer. Changes made in the sixth edition are based on resectability. Stages I and II represent respectable disease versus unresectable disease, and stages III and IV represent locally unre-sectable and metastatic disease, respectively. The AJCC sixth edition restaging may allow for better stratification when constructing clinical trials.

The presence of jaundice is a relatively common (see below) and ominous associated finding in patients with gallbladder cancer. Given the proximity of the gallbladder with the major extrahepatic biliary ductal structures, concomitant biliary involvement should not be surprising and can take the form of direct extension or metastatic disease to the hepatoduodenal ligament. The typical finding is obstruction of the distal common hepatic duct or proximal common bile duct, although involvement at the hepatic duct confluence or at the ampullary level may be seen. Coexisting jaundice generally implies advanced disease that is beyond resectability. In an analysis of 240 patients with gallbladder cancer over a seven-year period, Hawkins et al. reported the presence of jaundice in 82 (34%), of which only 6 (7%) had disease amenable to a complete resection, and all of these patients had either recurred or died of disease by two years. Additionally, the median survival in jaundiced patients was 6 months compared to 16 months in patients presenting without jaundice (133).

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