The objective of this study was to clarify the patterns of recurrence and prognosis after resection of intraductal papillary mucinous tumors (IPMTs). Fourteen patients with IPMT were reviewed histologically; intraductal papillary adenocarcinoma was present in 12 cases and intraductal papillary adenoma in 2. Six patients were alive with no evidence of disease. Two patients died from other causes. Six patients had recurrences. The median survival time was 46 months. In the six recurrent cases, the median postoperative disease-free interval was 38 months. Four patients died of recurrence, and the median survival time after recurrence was 6 months. The major site of recurrence was the remnant pancreas. The other sites were the liver in two cases, peritoneum in two, and local in one. These results suggest the multicentric or metachronous oncogenesis of IPMT. Because of the low frequency of lymph node metastases, an operation to preserve pancreatic function may be recommended, especially for localized tumors such as the branch type. It is important to avoid an incomplete resection using intraoperative pancreatoscopy and ultrasonography. Long-term follow-up after surgery is necessary even for a curative resection. We should perform total pancreatectomy for recurrences without distant metastases.

Hepatocellular carcinoma (HCC) is one of the most common malignancies in areas with endemic hepatitis virus infections, 1,2 which strongly suggests that hepatitis virus-related damage to the hepatocytes could contribute to HCC development. We demonstrated that the activity of hepatitis in chronic liver disease closely correlated with the intrahepatic recurrence after the operation of HCC. 3 Although the immunological mechanism in chronic hepatitis virus infection has not been clearly defined, it has been assumed that T-cellmediated cytotoxicity is responsible for the hepatocyte injury. In fact, the messenger RNA of the inflammatory cytokines, such as interferon gamma (IFN-␥) and interleukin-2, was preferentially detected in patients with increased hepatitis activity using reverse-transcriptase polymerase chain reaction (RT-PCR) in liver tissue. 4 Because HCC develops in chronic liver disease in which the host immune responses take place to excess, the escape from T-cell-mediated cytotoxicity is thought to be an essential role in the development and outgrowth of HCC.IFN-␥ is produced by activated T lymphocytes and naturalkiller cells, and plays an important role in the host defense mechanism by exerting antiviral, antiproliferative, immunoregulatory, and proinflammatory activities. 5-7 IFN-␥ exerts its pleiotrophic biological effects by transcriptional regulation of the expression of numerous genes, such as major histocompatibility complex (MHC) class I, FcrRI, and Fas through interaction with a specific cell membrane receptor (IFN-␥ receptor [IFN-␥-R]). 6,[8][9][10][11][12][13][14] Although the hepatocytes in the normal liver express weak or no IFN-␥-R, those in acute and chronic liver diseases up-regulated the expression of IFN-␥-R, and this up-regulation might play a partial role in the immunoregulatory action of IFN-␥ during liver inflammation. 15 Kaplan et al. demonstrated that IFN-␥-R ␣-chain knock-out mice developed tumors more rapidly and frequently than did the wild-type controls when bred onto a background deficient in the p53 tumor-suppressor gene, as well as when treated with the chemical carcinogen, 3-methylcolanthrene. 16 They proposed the concept that the actions of IFN-␥ on the tumor cells serve an extrinsic tumor-suppressor mechanism in immunocompetent hosts. Accordingly, blocking the signal transduction of IFN-␥ in HCC might contribute to escape from host immune surveillance in chronic liver disease in which many infiltrating lymphocytes produce IFN-␥. However, it is unclear how HCC blocks the signal transduction of IFN-␥. We examined the degree of tumor infiltration of IFN-␥-positive lymphocytes and the expression of IFN-␥-R, and IFN-␥-inducible genes, such as MHC class I and Fas, in HCC and investigated whether the modulation of IFN-␥-R expression was one of the mechanisms blocking the signal transducAbbreviations: HCC, hepatocellular carcinoma; IFN-␥, interferon gamma; RT-PCR, reverse-transcriptase polymerase chain reaction; MHC, major histocompatibility complex; IFN-␥-R, IFN-␥ receptor; AFP,...

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The cause of hemophilia is deficiency of coagulation factor VIII production in the liver, which can be cured by liver transplantation. Because the hepatic function of hemophilia patients is quite normal except for production of factor VIII, auxiliary partial orthotopic liver transplantation (APOLT) is beneficial in that patient survival is secured by preserving native liver even in the event of graft loss. However, it is not known whether the graft of APOLT would be enough to cure hemophilia. We evaluated the efficacy and feasibility of APOLT for hemophilia in a canine hemophilia A model that we established. Partial left liver graft was taken from the normal donor (blood factor VIII activity > 60%). The graft was transplanted to the hemophilia beagle dog (blood factor VIII activity < 5%) after resection of the left lobe preserving native right lobe. Changes in time of blood factor VIII activity and liver function parameters were observed after APOLT. APOLT and perioperative hemostatic management were successfully performed. The blood factor VIII activity increased to 30% after APOLT, and was sustained at least 6 weeks throughout the observation period without symptoms of bleeding. The result demonstrated sustained production of factor VIII in the hemophilia recipient after APOLT. Transplantation of approximately one third of whole liver resulted in cure of hemophilia. In conclusion, it is suggested that APOLT would be feasible as a curative treatment of hemophilia A to improve quality of life of the patients. (Liver Transpl 2005;11:579-584.)