Maehara Y

Impact of des-gamma-carboxy prothrombin and tumor size on the recurrence of hepatocellular carcinoma after living donor liver transplantation.

Backgrounds. Because many patients who did not meet the Milan criteria have survived long after undergoing living donor liver transplantation (LDLT), extended criteria for recipient with hepatocellular carcinoma (HCC) are therefore considered to be necessary. Methods and Results. A total of 90 consecutive adult LDLT recipients with HCC between 1996 and 2007 were reviewed. The recurrence-free survival rates of all 90 patients were 86.0%, 81.3%, and 81.3% at 1, 3, and 5 years, respectively. Fourteen of 90 patients developed a recurrence of tumor after the LDLT. The tumor recurrences were diagnosed within 1 year after the LDLT in 11 (78.6%) patients. In a multivariate analysis, both the tumor size of less than 5 cm (P=0.0202) and the des-gamma-carboxy prothrombin (DCP) level of less than 300 mAU/mL (P=0.0001) were found to be favorable independent factors for the recurrence of HCC after LDLT. Therefore, the authors devised new selection criteria for HCC patients (a tumor size of <5 cm or a DCP of <300 mAU/mL). The 1-, 3-, and 5-year overall or recurrence-free survival rates of the 85 patients who met the new criteria were 92.3%, 85.9%, and 82.7%, or 90.5%, 87.0%, and 87.0%, respectively, which were significantly different from those of the five patients who did not meet the new criteria (P<0.0001). Conclusions. A combination of two factors, namely the tumor size and the DCP level, was found to be useful for expanding the selection of LDLT candidates for HCC.

Improved Results of a Surgical Resection for the Recurrence of Hepatocellular Carcinoma After Living Donor Liver Transplantation

PurposeThis study was designed to analyze the clinical outcomes of the recurrence of hepatocellular carcinoma (HCC) after living donor liver transplantation (LDLT) and to evaluate the efficacy of a surgical resection in treating such a recurrence.MethodsA total of 101 adult LDLT recipients with HCC between 1996 and 2007, including 17 who had recurrent HCC, were reviewed. The endpoints analyzed were survival from time of transplant and survival from time of recurrence. Recipient demographics, laboratory valuables, and tumor characteristics were analyzed. Any medical or surgical treatments that had been administered for any recurrence also were considered.ResultsThe mean duration until the initial recurrence after LDLT and the mean duration until death after the initial recurrence were 12.9xa0months and 12.0xa0months, respectively. A univariate analysis showed that gender, interferon therapy, early posttransplant tumor recurrence, and eligibility for a surgical resection all had a beneficial impact on survival from tumor recurrence. A surgical resection of tumor relapse was the most important variable in our study, and therefore the patients were divided into two groups: surgical therapy group (nxa0=xa09), and nonsurgical therapy group (nxa0=xa07). Interestingly, the overall survival rates of the surgical group were significantly better than those of the nonsurgical group and were similar to that of the patients without HCC recurrence.ConclusionsSurgical therapy might be useful for patients who experience a recurrence of HCC after LDLT to improve their outcome, when such treatment is available.

Living Donor Hepatectomies with Procedures to Prevent Biliary Complications

BACKGROUNDnBiliary complications in donor hepatectomies are still common, and occur in approximately 5% of the procedures.nnnSTUDY DESIGNnTo evaluate the usefulness of the management and surgical procedures to prevent the biliary complications in donor hepatectomies, a total of 343 donors were retrospectively studied. The clinical and surgical parameters of the donors and the postoperative biliary complications were evaluated.nnnRESULTSnFourteen donors had biliary complication (BC) during the follow-up period (4.1%). Donors were divided into 2 groups; donors without BC (non-BC group; n = 329) and donors with BC (BC group; n = 14). Mean peak level of total bilirubin, mean duration of hospital stay after surgery, and medical cost in the BC group were significantly higher than in the non-BC group (p < 0.01). As improved procedures to prevent the BC were established at 2005, including the use of a real-time cholangiography by the C-arm, a minimized dissection of the hepatic vessels, the meticulous closure of the bile duct, and/or the use of Pringle maneuver during the parenchymal transection, the donors were divided into 2 groups before and after these establishments (the early period, n = 173; the later period, n = 170). Refinements in the management and surgical procedures reduced the occurrence of biliary complications from 6.4% during the early period to 1.8% during the later period (p < 0.01), and no biliary complications in the last 69 consecutive donors were observed.nnnCONCLUSIONSnTechnical refinements described in this study might be useful to prevent the occurrence of biliary complications in a donor hepatectomy. It is particularly important to preserve the blood supply for the biliary tract of both the graft and the remnant liver.

Living Donor Liver Transplantation Using Dual Grafts from Two Donors: A Feasible Option to Overcome Small-for-Size Graft Problems?

Living donor liver transplantation (LDLT) between adults inevitably implies two potential risks associated with a small‐for‐size graft for the recipient and small remnant liver for the donor. To overcome these problems, LDLT using dual grafts from two independent donors can be a solution, in which sufficient graft volume can be obtained while preserving donor safety. We present a case of LDLT that was managed successfully by using right and left lobe dual grafts from two donors. The recipient was a large‐size male with hepatitis C cirrhosis complicated by multiple hepatocellular carcinomas (HCCs). The first donor donated a right lobe graft and the second donor donated a left lobe plus caudate lobe graft with the middle hepatic vein. Graft function was excellent throughout the course without evidence of small‐for‐size syndrome. In conclusion, LDLT using dual grafts can be justified in a selected case to avoid small‐for‐size graft problems without increasing independent donor risks.

The long-term outcomes of patients with hepatocellular carcinoma after living donor liver transplantation: a comparison of right and left lobe grafts

PurposeThe feasibility of living donor liver transplantation (LDLT) using left lobe (LL) grafts has been demonstrated. However, the long-term outcome of the hepatocellular carcinoma (HCC) patients with LL grafts has not been elucidated. The aim of this study was to analyze the long-term outcomes after LDLT for HCC according to the graft type.MethodsA retrospective analysis was performed evaluating the outcomes of LL graft recipients (nxa0=xa082) versus recipients of RL grafts (nxa0=xa046). The analysis endpoints were the overall and recurrence-free survival after LDLT. The demographics of both recipients and donors, and the tumor characteristics associated with the graft type were also analyzed.ResultsThe graft volume (436xa0±xa074xa0g), as well as the graft volume-standard liver volume rate (38.3xa0±xa06.2%) of the LL graft group were significantly decreased as compared to those of the RL graft group (569xa0±xa082xa0g, 46.3xa0±xa06.7%; pxa0<xa00.01). The 1-, 3-, 5- and 7-year overall survival rates of the LL graft group were 88.2, 80.2, 75.7 and 72.4%, respectively, which were not significantly different compared to those of the RL graft group (95.4, 87.3, 87.3 and 87.3%). The recurrence-free survival rates of the LL graft group (89.1% at 1xa0year, 78.8% at 3xa0years, 75.8% at 5xa0years and 70.3% at 7xa0years) were similar to those of the RL graft group (88.6, 88.6, 88.6 and 88.6%). The mean peak postoperative total bilirubin levels and duration of hospital stay after surgery for the LL grafting donors were significantly decreased as compared to those of the RL grafting donors (pxa0<xa00.01). The rate of severe complications (over Clavien’s IIIa) associated with LL graft procurement was 6.2%, which was lower than that in the RL graft group (15.6%).ConclusionsThe long-term outcomes in the HCC patients with LL grafts were similar to those of patients receiving RL grafts, and the outcomes of the donors of LL grafts were more favorable. Therefore, LL grafts should be considered when selecting LDLT for HCC to ensure donor safety.

Hepatobiliary and Pancreatic: Pregnancy induced hepatic veno-occlusive disease requiring liver transplantation

A 22 year old women, who had an uneventful pregnancy, labor and vaginal delivery to a full-term normal baby, presented to the local hospital with abdominal bloating and derranged liver function test 5 months post-partum. Computed tomography (CT) revealed massive ascites and occlusion of the hepatic vein by thrombus involving the hepatic vein and inferior vena cava (Fig. 1). There was no portal vein thrombosis, nor were there features of portal hypertension. Laparoscopic liver biopsy was performed, which revealed veno-occlusive disease (VOD) (Fig. 2) on histopathological examination. There was massive necrosis of the hepatocytes in zone 3, and obstruction of the centrilobular vein was observed without portal area involvement. The patient had no past or family history of thrombosis and no history of taking any medication having thrombogenic properties. Her liver function was normal at an employment-related medical examination 3 years previously. She received anticoagulation therapy using heparin but developed jaundice and refractory ascites. She was transferred to our hospital for living donor liver transplantation (LDLT). CT revealed shrinking thrombus in the inferior vena cava (Fig. 1b). Laboratory results included a white blood cell count of 6240 per μL and platelet count of 254 000 per μL. Prothrombin time international normalized ratio was 1.5. Total serum bilirubin was 2.5 mg/dL, direct bilirubin 0.6 mg/dL, albumin 2.2 g/dL, aspartate aminotransferase 64 U/L, alanine aminotransferase 104 U/L, alkaline phosphatase 283 U/L, and gamma-glutamyltranspeptidase 38 U/L. Antinuclear antibody was negative, and proteins C and S activity were 22% and 30%, respectively. The model for end-stage liver disease score was 14 points; the Child–Pugh score was 11. She underwent living donor related liver transplant from her father’s right hepatic lobe. Biliary reconstruction was performed by duct-to-duct right hepaticohepaticostomy. She received tacrolumus, mycophenolate and steroid for immunosuppresion after the transplant. Histopathological evaluation of the whole liver revealed VOD. Severe necrosis of hepatocytes in the centrilobular zones was observed in the resected liver (Fig. 2b). There was fibrous occlusion of the central hepatic vein, and the relatively large hepatic vein was slightly damaged with fibrous change of the endothelium (Fig. 2c). The patient was transferred to a community hospital 20 days after liver transplantation with no recurrence of VOD. Although chemotherapy, alcohol, oral contraceptives, toxic oil, herbal medicine, and irradiation have been reported as risk factors for VOD, cytoreductive therapy prior to hematopoietic stem cell transplantation has become the most important and frequent cause of VOD, with an incidence of up to 70%. There are, however, no reports of pregnancy induced VOD that requires liver transplantation. The mechanism of VOD is reported as endothelial injury in both sinusoids and small hepatic venules by a toxic agent, which induces sloughing and downstream occlusion of terminal hepatic venules. In this patient, the cause of VOD was unclear, and there were no risk factors such as exposure to hepatotoxic agents and no history of previous liver disease. Pregnancy and delivery were the only possible causes. Autoimmunity during pregnancy may be associated with VOD; however, her workup was negative for these factors. Liver transplantation may be an option in patients who have no malignancy and are not responding to medical therapy. There are some reports describing VOD after liver transplantation; the prognosis is severe with 63% (12 of 19 patients) mortality.

Prognostic Markers for Immunochemotherapy Using Tegafur-Uracil (UFT) and Protein-Bound Polysaccharide K (PSK)

AIM/BACKGROUNDnWe previously reported that PSK-induced lymphocyte blastogenesis reaction (PSK-stimulation index; PSK-SI) may be a prognostic marker for immunochemotherapy using PSK in gastrointestinal cancer patients. In this study we evaluated the usefulness of PSK-SI as a prognostic marker for PSK therapy at higher and lower serum immunosuppressive acidic protein (IAP) levels.nnnPATIENTS AND METHODSn98 gastric and 135 colorectal cancer patients were analyzed. PSK-SI and serum IAP levels were measured preoperatively. After operation, patients received UFT and PSK for two years.nnnRESULTSnThere were no differences between patients with higher and those with lower PSK-SI with respect to the clinicopathological factors. In patients with higher serum IAP levels (> or = 500 microg/ml), recurrence-free survival (RFS) and overall survival (OS) were apparently more favorable in the higher PSK-SI group (gastric cancer; > or = 1.75, colorectal cancer; > or = 2.1) than in lower PSK-SI group, although the differences were not significant.nnnCONCLUSIONnSerum IAP levels and PSK-SI may be useful markers for prediction of response to immunochemotherapy using PSK, although further studies are necessary.