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A 69-year-old man diagnosed as having gallbladder cancer with liver invasion and metastasis to Couinaud's hepatic segment 8 (S8) was referred to our hospital. Because of the presence of liver metastasis, gemcitabine administration was chosen. Although gemcitabine was effective for the liver metastasis, his serum carcinoembryonic antigen (CEA) level had gradually increased after 12 cycles of gemcitabine administration. There was no distant metastasis other than the liver metastasis (manageable with gemcitabine) on detailed radiological examination. Therefore, we performed surgery for the primary lesion, after obtaining informed consent. Pathological examination demonstrated viable cancer cells with necrosis and fibrosis in the gallbladder, and fibrosis without viable cancer cells in the induration in liver S8. Gemcitabine was re-administered as postoperative adjuvant chemotherapy. Twenty months after the surgery, there was no sign of recurrence. In selected patients, gemcitabine treatment may be effective against gallbladder cancer with metastasis.

Lack of effective adjuvant therapy against advanced extrahepatic biliary tract carcinoma (BTC) requires that new therapeutic methods, such as molecular targeted therapy, be developed. The mitogen-activated protein kinase (MAPK) and Akt signaling pathways, which activate cell proliferation and suppress apoptosis, respectively, may function as important targets for such therapies. The aim of this study was to examine the expression patterns of phosphorylated MAPK (p-MAPK) and phosphorylated Akt (p-Akt) proteins in BTC cell lines and clinical specimens. Expression of p-MAPK and p-Akt proteins in four human BTC cell lines and in frozen sections of 20 advanced extrahepatic BTC specimens was analyzed by Western blotting. Thirty formalin-fixed BTC specimens were immunohistochemically stained for p-MAPK and p-Akt using labeled streptavidin–biotin conjugates. Expression of p-MAPK was observed in three of four (75%) BTC cell lines, whereas no expression of p-Akt was observed. Twenty-three of 30 formalin-fixed specimens stained positive for p-MAPK (77%), whereas only 47% stained positively for p-Akt. Expression of p-MAPK relative to that of p-Akt was also seen more frequently in the frozen specimens. The results of this study suggest that MAPK is activated more frequently than Akt in extrahepatic biliary tract carcinoma.

A 67-year-old woman was referred to our hospital for investigation of epigastric discomfort. Computed tomography (CT) showed dilatation of the intrahepatic bile duct in the left lobe of the liver, endoscopic cholangiography showed complete stenosis of the left main branch of intrahepatic bile duct, and CT during angiography showed decreased portal blood flow to segment 3 of the liver. Based on these findings, we suspected intrahepatic cholangiocarcinoma and performed left lobectomy of the liver. However, pathological examination revealed fibrosis and infiltration of inflammatory lymphoid cells around the stenotic bile duct and periportal area, without any evidence of malignancy. Since these findings were compatible with sclerosing cholangitis and the patient did not have a disorder that would cause secondary sclerosing cholangitis, the final diagnosis was primary sclerosing cholangitis (PSC). It is difficult to distinguish segmental PSC from cholangiocarcinoma; thus we think surgical resection is an appropriate therapeutic and diagnostic procedure for segmental intrahepatic bile duct stenosis.