SUMMARYBackgrounds: Neuroendocrine neoplasms in hepatobiliary organs are very rare, but several cases of

This study evaluated the usefulness of cone-beam computed tomography (CBCT) during ultraselective transcatheter arterial chemoembolization (TACE) for hepatocellular carcinomas (HCC) that could not be demonstrated on angiography. Twenty-eight patients with 33 angiographically occult tumors (mean diameter 1.3 +/- 0.3 cm) were enrolled in the study. The ability of CBCT during arterial portography (CBCTAP), during hepatic arteriography (CBCTHA), and after iodized oil injection (LipCBCT) to detect HCC lesions was retrospectively analyzed. The technical success of TACE was divided into three grades: complete (the embolized area included the entire tumor with at least a 5-mm wide margin), adequate (the embolized area included the entire tumor but without a 5-mm wide margin in parts), and incomplete (the embolized area did not include the entire tumor) according to computed axial tomographic (CAT) images obtained 1 week after TACE. Local tumor progression was also evaluated. CBCTAP, CBCTHA, and LipCBCT detected HCC lesions in 93.9% (31 of 33), 96.7% (29 of 30), and 100% (29 of 29) of patients, respectively. A single branch was embolized in 28 tumors, and 2 branches were embolized in five tumors. Twenty-seven tumors (81.8%) were classed as complete, and 6 (18.2%) were classed as adequate. None of the tumors were classed as incomplete. Twenty-five tumors (75.8%) had not recurred during 12.0 +/- 6.2 months. Eight tumors (24.2%), 5 (18.5%) of 27 complete success and 3 (50%) of 6 adequate success, recurred during 10.1 +/- 6.2 months. CBCT during TACE is useful in detecting and treating small HCC lesions that cannot not be demonstrated on angiography.

BACKGROUND: Similar to the pancreatic intraepithelial neoplasia (PanIN)-pancreatic carcinoma sequence model, intrahepatic cholangiocarcinoma (ICC) also reportedly follows a stepwise carcinogenesis process through the a precursor lesion: biliary intraepithelial neoplasia (BilIN). For this study, the authors investigated the status of v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) and GNAS complex locus (GNAS) mutations and tumor protein 53 (p53) overexpression in the stepwise process of cholangiocarcinogenesis. METHODS: Thirty patients with hepatolithiasis were surveyed, and their lesions were categorized as follows: non-neoplastic large bile duct (LBD) (n ¼ 12), peribiliary gland (PBG) (n ¼ 9), BilIN-1 (low-grade dysplasia; n ¼ 12), BilIN-2 (high-grade dysplasia; n ¼ 16), and BilIN-3 (noninvasive or in situ carcinoma; n ¼ 10). KRAS mutation at codons 12 and 13 and GNAS mutations at codons 601 and 602 were analyzed using genomic DNA extracted from isolated lesions by laser capture microdissection. Immunohistochemical expression of p53 also was evaluated in BilIN lesions, ICCs, and extrahepatic cholangiocarcinomas (ExCCs). RESULTS: A prevalence of KRAS mutations was identified in patients with ICC (31.5%), BilIN-3 (30%), and BilIN-2 (43.8%) compared with BilIN-1 (25%). Furthermore, KRAS mutations were detected in LBD lesions (41.7%) and PBG lesions (44.4%), and these mutations were observed with greater frequency in patients who had BilIN with KRAS mutations. GNAS mutations were not identified in any of the ICCs or other lesions examined. The overexpression of p53 was not identified in BilIN lesions and was less frequent in ICCs (18.2%) compared with ExCCs (38.1%) and gallbladder carcinomas (61.5%). CONCLUSIONS: KRAS mutations, which were present in approximately 33% of BilIN lesions, occurred as an early molecular event during the progression of BilIN to ICC, whereas p53 overexpression was identified as a late molecular event. Furthermore, the current results indicted that BilIN also may arise from LBD and PBG lesions in patients who have hepatolithiasis with KRAS mutations.

1IgG4 reactions consisting of marked infiltration by immunoglobulin G4 (IgG4)-positive plasma cells in affected organs is found in cancer patients as well as patients with IgG4-related diseases. Notably, extrahepatic cholangiocarcinomas accompanying marked IgG4 reactions clinicopathologically mimic IgG4-related sclerosing cholangitis. The regulatory cytokine interleukin (IL)-10 is thought to induce the differentiation of IgG4-positive cells. In this study, to clarify the mechanism of the IgG4 reaction in extrahepatic cholangiocarcinoma, we investigated nonprofessional antigen-presenting cells (APCs) generating IL-10-producing regulatory T cells (anergy T cells) and Foxp3-positive regulatory cells producing IL-10. Immunohistochemistry targeting IgG4, HLA-DR, CD80, CD86, and Foxp3 was performed using 54 cholangiocarcinoma specimens from 24 patients with gallbladder cancer, 22 patients with common bile duct cancer, and eight patients with cancer of the Papilla of Vater. Moreover, a molecular analysis of Foxp3 and IL-10 was performed using a cultured human cholangiocarcinoma cell line. Consequently, 43% of the cholangiocarcinomas were found to be abundant in IgG4. Those expressing HLA-DR but lacking costimulatory molecules (CD80 and CD86) and those expressing Foxp3 detected by an antibody recognizing the N terminus accounted for 54% and 39% of cases, respectively. Moreover, the number of IgG4-positive cells was larger in these cases than in other groups. In cultured cells, the presence of a splicing variant of Foxp3 messenger RNA and the expression of IL-10 were demonstrated. Conclusion: Extrahepatic cholangiocarcinoma is often accompanied by significant infiltration of IgG4-positive cells. Cholangiocarcinoma cells could play the role of nonprofessional APCs and Foxp3-positive regulatory cells, inducing IgG4 reactions via the production of IL-10 indirectly and directly, respectively. (HEPATOLOGY 2012;56:157-164) B iliary tract cancers can be anatomically divided into intrahepatic and extrahepatic cholangiocarcinomas, the latter including hepatic hilar cancer, common bile duct cancer, gallbladder cancer, and cancer of the Papilla of Vater. The biological behavior and carcinogenesis of each cancer differ, but the histology of most biliary tract cancers is the same as that of ordinary adenocarcinomas. In addition to neoplastic lesions, several types of cholangitis causing biliary stenosis are important in the differential diagnosis of biliary diseases. Particularly, primary sclerosing cholangitis and a complication of immunoglobulin G4 (IgG4)-related systemic diseases, IgG4-related sclerosing cholangitis, clinicopathologically mimic extrahepatic cholangiocarcinomas.IgG4 is a minor immunoglobulin subtype composing 3%-6% of all the IgG circulating in adults, 1 but is important for a systemic disorder, IgG4-related disease, that features elevated serum IgG4 levels and abundant

No abstract