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BACKGROUND.: Although the outcome of liver transplant patients with hepatocellular carcinoma (HCC) has improved with the introduction of strict criteria, tumor recurrence still remains a significant problem. Sphingosine-1-phosphate (S1P) is a phospholipid mediator that can induce diverse cellular responses, such as proliferation, migration, adhesion, and cell-rounding, in cancer cells. We investigated whether FTY720, a S1P analog, suppresses tumor recurrence after experimental liver transplantation in a rat HCC model. METHODS.: HCC-bearing rats were subjected to orthotropic liver transplantation. HCC cells were analyzed for cell migration, proliferation, and S1P receptors. RESULTS.: FTY720 induced the down-regulation of the S1P-1 receptor of HCC cells and suppressed both cancer cell migration and proliferation. FTY720 also suppressed mitogen-activated protein kinase phosphorylation. The suppression of tumor recurrence after liver transplantation and a significant prolongation of survival were observed in the FTY720-treated rats, in comparison with FTY720-untreated rats. CONCLUSION.: FTY720 suppresses the invasiveness and proliferation of HCC through a down-regulating S1P-1 receptor to suppress the recurrence of HCC after liver transplantation; FTY720 may be used as a new antimetastatic agent for the prevention of tumor recurrence after liver transplantation.

Summary Currently, patients are prescribed lifelong treatment with hepatitis B immunoglobulin (HBIg) after liver transplantation (LT) for hepatitis B virus (HBV)-related diseases in order to prevent reinfection with HBV. Active immunization with an HBV vaccine would be a preferable alternative; however, the immunosuppressive environment in LT recipients is believed to elicit a poor response to vaccination. Minimizing the exposure of the HBV-infected LT recipients to immunosuppressants would be beneficial in inducing adaptive immunity against HBV by vaccination. In this study, in addition to efforts to minimize immunosuppression, prophylaxis with HBV vaccination combined with continuous HBIg administration was performed in 17 LT recipients who had undergone transplantation attributable to HBV-related diseases. During the observation period, the overall response rate to HBV vaccination was 64.7%. The immune status of the recipients was evaluated by a mixed lymphocyte reaction assay in response to allostimulation. Patients showing a donor-specific hyporesponse with a well-maintained response to the third-party stimulus always achieved a sustained immune response to the vaccine, whereas patients showing a hyporesponse to both the donor and the third-party stimulus were unable to do so. Thus, inducing an anti-donor-specific immunosuppressive status by minimizing immunosuppression should enable post-transplant HBV vaccination to be a promising prophylactic strategy.

Biliary stricture remains a significant cause of morbidity after liver transplantation. We performed duct-to-duct biliary anastomosis by using an absorbable stent tube with a diameter equal to that of pig common bile duct as an internal stent. The stent tube was constructed using a synthetic biodegradable material-a lactic glycolic acid and epsilon-caprolactone copolymer. Three pigs were alive without cholestasis for 180 d; however, 1 pig died on the 65th postoperative d, and autopsy revealed no cholestasis or biliary sledge in the biliary stent tube. The 3 pigs were euthanized for histological examinations 180 d after surgery; the biliary stent tube was completely absorbed by this time. These experimental results showed the good patency of the absorbable biliary stent tube. In the future, the absorbable biliary stent tube is expected to be clinically developed as a biliary stent for biliary anastomosis, which may protect the biliary anastomotic stricture.

Background. Congestion in the right paramedian sector of a right liver graft without a middle hepatic vein (MHV) may lead to graft dysfunction. To solve this problem, we have developed a technique for reconstructing the MHV tributaries of the right liver grafts by using the preserved recipient's native MHV trunk. Methods. Between 2005 and 2007, among 34 right liver graft liver transplant patients with significant MHV tributaries (>5 mm in diameter), 21 patients underwent right liver graft living-donor liver transplantation: draining MHV tributaries with recipient's native MHV trunk. We evaluated the patency of the reconstructed MHV tributaries, graft regeneration, and graft survival. Results. The 3-month patency rates of the reconstructed V8 and V5 were 92% and 76%, respectively. The 1-year survival rate and the regeneration index of the right paramedian sector 6 months after transplantation were higher in patients with reconstructed MHV tributaries than that for patients without reconstructed MHV tributaries. Conclusion. The use of the recipient's MHV trunk for the reconstruction of the MHV tributaries of the right liver grafts is considered to be a valuable and a feasible strategy in right liver graft living-donor liver transplantation.

The purpose of the study was to compare the abilities of the JIS and modified JIS (m-JIS) scores to predict survival after hepatectomy for hepatocellular carcinoma (HCC).Data for patients who underwent hepatectomy for HCC at Hiroshima University Hospital between 1986 and 2006 were included. The overall survival and disease-free survival were calculated by the Kaplan-Meier method, and differences between groups were tested by the log-rank test. The statistics of the Akaike information criterion (AIC) were used to show the more appropriate model.A total of 626 patients were included (male/female, 468/158; mean age, 63.4+/-9.6 years; Child-Pugh class A/B, 524/102; liver damage grade A/B/C, 356/261/9). Mean survival and disease-free survival were 8.04+/-0.39 and 4.69+/-0.32 years, respectively. There was a significant difference in the overall survival rate between JIS scores 1 and 2, and 2 and 3 (P0.05), but not between scores 0 and 1, or 3 and 4 (P0.05). Except between m-JIS scores 0 and 1, there was excellent discriminatory ability in overall survival rate between other consecutive groups. Concerning disease-free survival, a significant difference was found only between JIS scores 1 and 2. However, the disease-free survival rate could be well differentiated between m-JIS scores 1 and 2, and 3 and 4. The m-JIS score had a higher discriminatory ability, indicated by a linear trend analysis, and a higher homogeneity likelihood ratio, and lower AIC statistics, than the original JIS score in predicting both overall and disease-free survival.The modified-JIS scoring system using liver damage grade is better than the original JIS scoring system in predicting survival after hepatectomy for HCC in Japan.

Splenic artery steal syndrome (SASS) has only recently been recognized as a potential threat to transplanted livers. We report a case of SASS with progressive liver dysfunction that developed after living donor right lobe liver transplantation. SASS suspected by serial pre- and postoperative computed tomographic (CT) scans was diagnosed by celiac trunk angiography. It was successfully salvaged by splenic artery embolization. In this case, serial examinations of CT scans were useful to diagnose SASS. This case showed that portal hyperperfusion injury is a cause of liver graft dysfunction in SASS. The splenic artery embolization technique is a safe procedure that can be applied to treat such injury.

Tumor recurrence after liver transplantation still remains a significant problem in patients with hepatocellular carcinoma. The small GTPase Rho/Rho-associated kinase (ROCK) pathway is involved in the motility and invasiveness of cancer cells. We investigated whether tacrolimus activated the Rho/ROCK signal pathway to promote the invasiveness of rat hepatocellular carcinoma cells. We also investigated whether the ROCK inhibitor Y-27632 suppressed tumor recurrence after experimental liver transplantation in a rat hepatocellular carcinoma model. Orthotopic liver transplantation was performed in hepatocellular carcinoma cell line McA-RH7777-bearing rats. Tacrolimus was administered to liver transplant rats and these rats were divided into two groups: the Y-27632-treated (10 mg/kg, for 28 days) group and the Y-27632-untreated group. Tacrolimus enhanced the cancer cell migration and stimulated phosphorylation of the myosin light chain (MLC), a downstream effector of Rho/ROCK signaling. Y-27632 suppressed the cancer cell migration and tacrolimus-induced MLC phosphorylation. Suppression of tumor recurrence after liver transplantation and significant prolongation of survival were observed in the Y-27632-treated rats in comparison with theY-27632-untreated rats. Tacrolimus stimulates the Rho/ROCK signal pathway to enhance the invasiveness of hepatocellular carcinoma, and the ROCK inhibitor Y-27632 can be used as a new antimetastatic agent for the prevention of tumor recurrence after liver transplantation.

症例は33歳の男性. 発熱と腹痛を主訴に来院した. 腹部CT検査にて腸間膜脂肪織に脂肪濃度上昇が見られた. 腸間膜脂肪織炎を疑うも, 確定診断の目的にて開腹手術を行った. 術中, 腸間膜脂肪織炎と判断し, 肥厚した腸間膜およびリンパ節の生検および腹腔ドレナージを行い閉腹した. 病理組織学的にも腸間膜脂肪織炎との診断であった. 術後, 抗生剤投与にても炎症所見遷延したため, 第7病日より10mg/日のステロイド投与を開始し速やかな炎症反応の改善を認めた. 腸間膜脂肪織炎は原因不明のまれな非特異性炎症性疾患であり, 確立した治療法はない. 今回, 我々は低用量のステロイド投与が有効であったと思われる1例を経験したので文献的考察を加え報告する.

Background: Splenectomy is gaining increasing importance for cirrhotic patients with hypersplenism. However, its safety and efficacy for patients with chronic liver disease remain unclear. Methods: We retrospectively examined the medical records of 38 consecutive cirrhotic patients who underwent splenectomy or simultaneous hepatectomy and splenectomy for hepatocellular carcinoma. Results: White blood cell and platelet counts significantly increased 3 months after splenectomy. Serum levels of total bilirubin and prothrombin time significantly improved 1 year after splenectomy. Interferon therapy was administered to 25 patients after splenectomy. A sustained viral response was achieved in 8 patients (42%). The total incidence of portal or splenic vein thrombosis (PSVT) detected by postoperative dynamic computed tomography was 13/38 (34.2%). Multivariate analysis revealed preoperative spleen volume (SV) to be the sole independent predictor of postoperative PSVT. Receiver-operator characteristic curve analysis showed that a cut-off SV of 450 ml corresponded to a sensitivity of 85% and a specificity of 56%. Conclusions: Splenectomy improved the liver function and facilitated effective interferon therapy in cirrhotic patients with hypersplenism, although preoperative SV was frequently associated with postoperative PSVT.

A 62-year-old man underwent right hepatectomy with resection of the middle hepatic vein trunk for metastatic liver cancers. Serious congestion of the caudal area of segment 4 occurred just after dividing the middle hepatic vein trunk. The reconstruction of the venous tributary from the caudal area of segment 4 to the inferior vena cava was performed using a saphenous vein graft of 11 cm in length. The congestion of the corresponding area improved just after the accomplishment of reconstruction, and the patient's postoperative course was uneventful. Serious congestion of the remnant liver observed in this case would occur rarely in the usual setting, because the stagnant blood flows backward to the portal branches or the intrahepatic venous anastomoses. In this case, the middle hepatic artery had been occluded by a steel coil for the treatment. Consequently, the occlusion of the middle hepatic artery have resulted in the serious congestion, because the portal branches to the caudal area of segment 4 were inflow vessels, not outflow ones, after division of the middle hepatic vein trunk. This is the first report on serious congestion of the caudal area of segment 4 and reconstruction of the venous tributary.

Although antiviral prophylaxis with the combined high-dose hepatitis B immunoglobulin (HBIg) and lamivudine therapy has effectively reduced post-liver transplantation recurrence of hepatitis B virus infection, its use is limited by cost and availability.Fourteen living-donor liver transplant patients were performed with the mean follow-up of the 23 months (range, 5 to 58 months). We examined the effectiveness of prophylaxis against recurrence of hepatitis B with much lower dose of HBIg. HBIg (10000 IU/day) was two or three times intra- and postoperatively administered and then the serum titers of HBIg was maintained at more than 100 IU/mL.Although two patients were preoperatively HBV-DNA positive (DNA concentrations were 4.4 and 4.7 LGE, respectively) by a transcription-mediated amplification assay (TMA) method, all 14 patients postoperatively became HBV-DNA-negative and HBsAg-negative.Our protocol of the combination low-dose HBIg and lamivudine therapy prevents the recurrence of hepatitis B and is likely to be more cost-effective than high-dose HBIg regimens. Further study is needed to develop the combination therapy of the optimal dose of HBIg and lamivudine.