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Background: Signal regulatory protein alpha (SIRPα), expressed in the macrophage membrane, inhibits phagocytosis of tumor cells via CD47/SIRPα interaction, which acts as an immune checkpoint factor in cancers. This study aimed to clarify the clinical significance of SIRPα expression in hepatocellular carcinoma (HCC)., Methods: This study analyzed SIRPα expression using RNA sequencing data of 372 HCC tissues from The Cancer Genome Atlas (TCGA) and immunohistochemical staining of our 189 HCC patient cohort. The correlation between SIRPα expression and clinicopathologic factors, patient survival, and intratumor infiltration of immune cells was investigated., Results: Overall survival (OS) was significantly poorer with high SIRPα expression than with low expression in both TCGA and our cohort. High SIRPα expression correlated with lower recurrence-free survival (RFS) in our cohort. High SIRPα expression was associated with higher rates of microvascular invasion and lower serum albumin levels and correlated with greater intratumor infiltration of CD68-positive macrophages and myeloid-derived suppressor cells (MDSCs). Multivariate analysis showed that SIRPα expression and high infiltration of CD8-positive T cells and MDSCs were predictive factors for both RFS and OS. Patients with high SIRPα expression and infiltration of CD8-positive T cells and MDSCs had significantly lower RFS and OS rates. In spatial transcriptomics sequencing, SIRPα expression was significantly correlated with CD163 expression., Conclusions: High SIRPα expression in HCC indicates poor prognosis, possibly by inhibiting macrophage phagocytosis of tumor cells, promoting MDSC infiltration and inducing antitumor immunity. Treatment alternatives using SIRPα blockage should be considered in HCC as inhibiting macrophage antitumor immunity and MDSCs., (© 2023. Society of Surgical Oncology.)

Background: Antiangiogenic tyrosine kinase inhibitors (TKIs) provide one of the few therapeutic options for effective treatment of hepatocellular carcinoma (HCC). However, patients with HCC often develop resistance toward antiangiogenic TKIs, and the underlying mechanisms are not understood. The aim of this study was to determine the mechanisms underlying antiangiogenic TKI resistance in HCC., Methods: We used an unbiased proteomic approach to define proteins that were responsible for the resistance to antiangiogenic TKIs in HCC patients. We evaluated the prognosis, therapeutic response, and serum insulin-like growth factor-binding protein-1 (IGFBP-1) levels of 31 lenvatinib-treated HCC patients. Based on the array of results, a retrospective clinical study and preclinical experiments using mouse and human hepatoma cells were conducted. Additionally, in vivo genetic and pharmacological gain- and loss-of-function experiments were performed., Results: In the patient cohort, IGFBP-1 was identified as the signaling molecule with the highest expression that was inversely associated with overall survival. Mechanistically, antiangiogenic TKI treatment markedly elevated tumor IGFBP-1 levels via the hypoxia-hypoxia inducible factor signaling. IGFBP-1 stimulated angiogenesis through activation of the integrin α5β1-focal adhesion kinase pathway. Consequently, loss of IGFBP-1 and integrin α5β1 by genetic and pharmacological approaches re-sensitized HCC to lenvatinib treatment., Conclusions: Together, our data shed light on mechanisms underlying acquired resistance of HCC to antiangiogenic TKIs. Antiangiogenic TKIs induced an increase of tumor IGFBP-1, which promoted angiogenesis through activating the IGFBP-1-integrin α5β1 pathway. These data bolster the application of a new therapeutic concept by combining antiangiogenic TKIs with IGFBP-1 inhibitors., (© 2023 The Authors. Cancer Communications published by John Wiley & Sons Australia, Ltd. on behalf of Sun Yat-sen University Cancer Center.)

Recurrence of hepatocellular carcinoma (HCC) after living donor liver transplant (LDLT) is an essential factor defining prognosis, and surgical resection is the only curative treatment. However, the factors that define whether surgical resection is possible remain unclear. Here, we compared resectable and unresectable HCC recurrence cases after LDLT and examined factors that determine whether surgical resection is possible. Resectable (n = 17) and unresectable (n = 14) groups among 264 patients who underwent LDLT for HCC from January 1999 to March 2020 were compared and examined for recurrence type, prognosis, and clinicopathologic factors. Overall survival after LDLT (median, 8.5 vs 1.7 years, P < .01) was significantly longer in the resectable group. In univariate analysis, female recipient rate, lymphocyte to monocyte ratio (LMR) ≥2.75, and tumor size ≤5.0 cm were significantly higher in the resectable group. Younger donors, lower Model for End-Stage Liver Disease scores, lower graft volume, and lower graft volume to standard liver volume ratio were evident in the resectable group. In multivariate analysis, female recipient rate (P = .0034) and LMR ≥2.75 (P = .0203) were independent predictive factors for resectable HCC recurrence after LDLT. Female recipient and LMR ≥2.75 before transplant could predict the surgically resectable type of HCC recurrence after LDLT., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: There is little evidence concerning survival after surgery in patients with hepatocellular carcinoma who have received lenvatinib treatment. The aim of this study was to evaluate whether post-lenvatinib surgical treatment in patients with hepatocellular carcinoma improves overall survival., Methods: The cohort of this retrospective study comprised 55 patients with hepatocellular carcinoma who had undergone lenvatinib treatment. We classified them into two groups according to post-lenvatinib surgical treatment status and compared clinicopathologic factors and prognosis between the two groups with the aim of identifying predictors of overall survival., Results: The median duration of lenvatinib administration was 5.8 months (range, 0.4-24.0 months). Twelve of the 55 patients underwent surgery after receiving lenvatinib. There was no significant difference in assessed clinicopathological factors between patients who did and did not undergo surgery after being treated with lenvatinib. Multivariate analysis revealed that older age was associated with a significantly worse overall survival (hazard ratio: 2.332; 95% confidence interval 1.062-5.168; P = 0.0369) and that surgery after treatment with lenvatinib achieved better overall survival than other forms of treatment (hazard ratio: 0.121; 95% confidence interval 0.016-0.901; P = 0.0393)., Conclusions: Surgical treatment after lenvatinib administration may be a useful therapeutic option for select patients with hepatocellular carcinoma., (© 2022. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Background: Expanding patient selection beyond the Milan criteria in living donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC) has long been a matter for debate. We have used the Kyushu University Criteria - maximum tumor diameter <5 cm or des-γ-carboxy prothrombin <300 mAU/ml - in LDLT for HCC since June 2007. The aim of the present study was to present the results of our prospective patient selection by Kyushu University Criteria and to confirm whether or not our criteria were justified., Methods: The entire study period was divided into the pre-Kyushu era (July 1999-May 2007) and the Kyushu era (June 2007-November 2014). Eighty-nine and 90 patients underwent LDLT for HCC in the pre-Kyushu era and the Kyushu era, respectively., Results: In the pre-Kyushu era, there were significant differences in recurrence-free and disease-specific survival between the beyond-Milan and the within-Milan patients. In the Kyushu era, however, the differences in recurrence-free and disease-specific survival between the beyond-Milan and the within-Milan patients disappeared. The 5-year overall patient survival in the Kyushu era was 89.4%., Conclusion: Our selection criteria enabled a considerable number of beyond-Milan patients to undergo LDLT without jeopardizing the recurrence-free, and disease-specific, and overall patient survival., (Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Refractory ascites is a serious post-hepatectomy complication in cirrhotic patients with hepatocellular carcinoma (HCC). In order to avoid this complication, surgeons should preserve as much liver parenchyma as possible in performing hepatectomy in such patients. However, we still occasionally encounter refractory ascites even after limited or small hepatectomy. The aim of this study was to identify risk factors for post-hepatectomy refractory ascites in cirrhotic patients, focusing on limited or small hepatectomy., Patients and Methods: The data of 73 cirrhotic patients with HCC who underwent limited or small hepatectomy were analyzed. Limited or small hepatectomy was defined as hepatectomy equal to or of less than subsegmentectomy. We compared the clinicopathological factors between patients with and without postoperative refractory ascites., Results: Fourteen cirrhotic patients suffered postoperative refractory ascites. Total cholesterol, duration of operation, duration of Pringle maneuver, resection of segment VII, intraoperative blood loss, and intraoperative blood transfusion were found to be significant risk factors for postoperative refractory ascites in univariate analyses. Multivariate analysis revealed that resection of segment VII was an independent risk factor., Conclusion: Resection of segment VII necessitates extensive dissection of the right triangular or coronary ligaments, which could explain that it was an independent risk factor for post-hepatectomy refractory ascites. Surgeons should avoid extensive dissection of these ligaments in order to avoid this detrimental complication., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

There are few reports about recurrence-related microRNAs (miRNAs) after liver transplantation (LT) for hepatocellular carcinoma (HCC). The purpose of this study was to identify novel recurrence-related miRNAs after living donor liver transplantation (LDLT) for HCC. First, we performed microarray analyses of samples from a liver with primary HCC, a liver that was noncancerous, and a liver that had recurrence-metastasis from 3 patients with posttransplant recurrence. Then we selected miRNAs with consistently altered expression in both primary HCC and recurrence as potential candidates of recurrence-related miRNAs. Expression of the miRNAs in HCC and noncancerous livers was assessed in 70 HCC patients who underwent LDLT. The target genes regulated by the recurrence-related miRNAs were identified. MicroRNA-18a (miR-18a) expression was increased, and microRNA-199a-5p (miR-199a-5p) expression was decreased in both primary HCC and recurrence. Increased miR-18a expression correlated with high levels of tumor markers, large tumor size, and a high recurrence rate. Decreased miR-199a-5p expression correlated with high levels of tumor markers, portal venous invasion, and a high recurrence rate. In HCC cells, miR-18a regulated the expression of tumor necrosis factor alpha-induced protein 3 (TNFAIP3), and miR-199a-5p regulated the expression of hypoxia-inducible factor 1 alpha (HIF1A), vascular endothelial growth factor A (VEGFA), insulin-like growth factor 1 receptor, and insulin-like growth factor 2. In conclusion, increased miR-18a levels and decreased miR-199a-5p levels are relevant to HCC recurrence after LDLT. MiR-18a and miR-199a-5p could be novel therapeutic targets of recurrent HCC after LDLT. Liver Transplantation 22 665-676 2016 AASLD., (© 2016 American Association for the Study of Liver Diseases.)

Background: Transecting cirrhotic liver in pure laparoscopic hepatectomy (PLH) is generally considered technically demanding. We have preferentially used BiClamp in PLH by fracturing liver parenchyma using this device. The aim of the current study was to retrospectively verify the efficacy of BiClamp-fracture method in transecting cirrhotic parenchyma., Methods: The medical records of 21 patients who underwent PLH using BiClamp-fracture method between April 2011 and September 2014 were examined. The patients were divided into the Nonstiff group (F0-F2, n=11) and the Stiff group (F3 and F4, n=10) and various surgical factors were compared between the groups., Results: The mean operation time, the mean intraoperative blood loss, and the mean postoperative hospital stay in the Stiff group were comparable with those in the Nonstiff group. There were no postoperative complications in both groups., Conclusion: BiClamp-fracture method was effective in transecting liver parenchyma irrespective of liver stiffness in PLH.

Background: Pure laparoscopic liver resection is technically difficult for tumors located in the dorsal anterior and posterior sectors. We have developed a maneuver to perform pure laparoscopic hepatectomy in the semiprone position which was developed for resecting tumors located in these areas., Methods: The medical records have been reviewed retrospectively in 30 patients who underwent laparoscopic liver resection in the semiprone position for carcinoma in the dorsal anterior or posterior sectors of the right liver between 2008 and 2011., Results: Seventeen liver tumors were primary liver tumors and 13 were colorectal metastases. Of the 30 patients, 11 (36.6 %) underwent major hepatectomy [right hemihepatectomy in 7 (23.3 %) and posterior sectionectomy in 4 (13.3 %)]. Anatomical minor resection, such as S6 or S7 segmentectomy, was performed in five patients (16.6 %). Five patients with liver metastasis underwent a simultaneous laparoscopic resection. There was no mortality, reoperation, or conversion to open procedures. There were no hepatectomy-related complications such as postoperative bleeding, bile leakage, or liver failure., Conclusions: Pure laparoscopic hepatectomy in the semiprone position for tumors present in the dorsal anterior and posterior sectors is feasible and safe. This method expands the indications for laparoscopic liver resection for tumors.

The outcome after surgical resection for intrahepatic cholangiocarcinoma has not been satisfactorily evaluated due to its malignant behavior. Surgical resection, however, has the potential to improve the prognosis and may allow surgeons to experience rare cases with long survival. This report presents the case of a patient who developed recurrence 9 years after resection of intrahepatic cholangiocarcinoma. A 76-year-old female was diagnosed to have intrahepatic cholangiocarcinoma and underwent an extended right posterior subsegmentectomy. The gross appearance showed a mass-forming type tumor. The histopathological examination revealed well to moderately differentiated adenocarcinoma associated with portal vein invasion. Subcutaneous metastasis in the head as the first sign of relapse was diagnosed 9 years after hepatectomy. The histopathological findings of the subcutaneous tumor were similar to those of the intrahepatic cholangiocarcinoma, thus suggesting metastasis from intrahepatic cholangiocarcinoma. Positron emission tomography with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose was useful for detecting multiple metastases. Long-term follow-up for more than 5 years is recommended because the present case shows that late recurrence of intrahepatic cholangiocarcinoma occurs even 5 years after resection.

Background: The effects of preoperative lipiodolization (LPD) for large hepatocellular carcinoma (HCC) are controversial., Methods: A retrospective review was undertaken for 137 patients with initial solitary resectable HCC ≥ 5 cm who underwent hepatic resection between 1995 and 2008. Forty-two patients underwent preoperative LPD, and clinical data and prognosis were compared to those of patients without preoperative LPD (n=95)., Results: Surgical results of the LPD group, such as surgical time, surgical blood loss, and the mortality and morbidity rate were statistically equal to those of the nonLPD group. The disease-free and overall survival of the LPD group were significantly better than those of the nonLPD group, and early tumor recurrence within 1-year of the LPD group was significantly lower than that of the nonLPD group. According to the multivariate analysis, the absence of preoperative LPD was an independent poor prognostic factor of patients with hepatic resection for HCC ≥ 5 cm., Conclusion: Preoperative LPD suppressed early tumor recurrence and improved patient survival after hepatic resection for HCC ≥ 5 cm., (Copyright © 2012 Wiley Periodicals, Inc.)

Purpose: The 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., Methods: A retrospective analysis was performed evaluating the outcomes of LL graft recipients (n = 82) versus recipients of RL grafts (n = 46). 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., Results: The graft volume (436 ± 74 g), as well as the graft volume-standard liver volume rate (38.3 ± 6.2%) of the LL graft group were significantly decreased as compared to those of the RL graft group (569 ± 82 g, 46.3 ± 6.7%; p < 0.01). 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 1 year, 78.8% at 3 years, 75.8% at 5 years and 70.3% at 7 years) 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 (p < 0.01). 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%)., Conclusions: The 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.

Objective: To clarify the predictive impact of expanded criteria for liver transplantation (LT) for patients with hepatocellular carcinoma (HCC) in 54 patients with HCC beyond the Milan criteria (MC) from a series of 109 consecutive living-related donor liver transplantation (LDLT) recipients with HCC., Methods: Among 54 patients with HCC exceeding the MC, the predictive values for HCC recurrence within expanded criteria comprising the UCSF, Tokyo, Kyoto, Kyushu University (based on the tumor size and des-gamma carboxy prothrombin level) and Up-to-seven criteria were compared using univariate and multivariate analyses. The histological characteristics of HCC were compared among these extended criteria., Results: All five criteria were significant predictors for recurrence-free survival after univariate analyses. The Kyushu University criteria were the most powerful predictive criteria for HCC recurrence after multivariate analyses. The incidence of microvascular invasion and poorly differentiated HCC was significantly higher in patients with HCC exceeding the Kyushu University criteria than in those with HCC within the criteria., Conclusions: Compared with the other expanded criteria, the Kyushu University criteria may be useful to eliminate LT candidates at very high risk of HCC recurrence. The Kyushu University criteria were useful to evaluate LT candidates with HCC., (© 2011 John Wiley & Sons A/S.)

Background: The object of the current study was to review the outcomes of hepatic resection for hepatocellular carcinoma (HCC) ≥ 10 cm., Methods: Between 1995 and 2007, fifty-three patients with HCC ≥ 10 cm underwent hepatic resection, and clinical data were compared to those of patients with non-surgical treatment (n = 12). Surgical results for HCC ≥ 10 cm were compared to those of patients with HCC < 10 cm (n = 412). The independent poor prognostic factors of the patients with HCC ≥ 10 cm were identified., Results: Overall survival was significantly better in patients with hepatic resection for HCC ≥ 10 cm than in those with non-surgical treatment (P < 0.01). Survival rates of patients with hepatic resection for HCC ≥ 10 cm were 35% at 5 years. Morbidity and mortality rate were statistically equal. The independent poor prognostic factors of patients with hepatic resection for HCC ≥ 10 cm were revealed: T4 status, macroscopic tumor thrombus in portal vein (VP+), and the use of intra-operative transfusion., Conclusion: Hepatic resections for HCC ≥ 10 cm are safe and efficacious. Minimizing intra-operative blood loss and the establishment of an effective systemic treatment for patients with HCC ≥ 10 cm in T4 appear to be critical., (Copyright © 2011 Wiley-Liss, Inc.)

Purpose: Diaphragmatic involvement is relatively uncommon in patients undergoing a hepatectomy for hepatocellular carcinoma (HCC). The aim of this study was to evaluate the short- and long-term surgical impacts of HCC with gross diaphragmatic involvement in patients undergoing an en bloc resection of the diaphragm., Methods: Between 1990 and 2007, 911 patients with HCC underwent a hepatectomy at our institution. Twenty-seven patients (3.0%) had had gross involvement of the diaphragm. Thirteen patients (1.4%) had undergone an en bloc resection of the diaphragm, and 14 (1.5%) had received only a blunt dissection. The short-term surgical impacts (surgical morbidity and mortality) and long-term surgical impacts (overall and disease-free survival) were compared between the groups., Results: In patients with an en bloc resection of the diaphragm as compared with those who received a blunt dissection, the values of total bilirubin and the indocyanine green retention rate at 15 min were significantly better (P < 0.01 and P = 0.04, respectively), and the rate of positivity for the hepatitis B antigen was significantly higher (P = 0.02). The positive rates of microscopic fibrocapsular invasion (P = 0.03), microscopic vascular invasion (P = 0.04), and Ki-67 immunostaining (P = 0.04) were significantly higher in patients with an en bloc resection of the diaphragm. There were no significant differences in the short-term and long-term surgical impacts between the groups., Conclusion: An en bloc resection of the diaphragm in patients with gross diaphragmatic involvement of HCC is therefore justified, since there are no significant differences in short- or long-term surgical impacts in comparison with the patients receiving blunt dissection.

Purpose: This 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., Methods: A 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., Results: The mean duration until the initial recurrence after LDLT and the mean duration until death after the initial recurrence were 12.9 months and 12.0 months, 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 (n = 9), and nonsurgical therapy group (n = 7). 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., Conclusions: Surgical therapy might be useful for patients who experience a recurrence of HCC after LDLT to improve their outcome, when such treatment is available.

Purpose: Lipiodol Ultra-Fluid (Lipiodol(®)), an oily contrast medium, is selectively retained in hepatocellular carcinoma (HCC) through hepatic arterial infusion. DDP-H (IA-call(®)) developed as a CDDP powder, and may be a possible chemotherapeutic agent with lipiodol. We carried out a phase I/II study of the lipiodolization using DPP-H in patients with unresectable HCC., Methods: Phase I and pharmacokinetic study: The dose-limiting toxicity (DLT), the maximum tolerance dose (MTD), and the recommended dose (RD) were determined using a modified Fibonacci scheme. The concentration-time profile of total platinum in plasma was analyzed. Phase II study: Thirty-five patients with unresectable HCC received lipiodolization using DDP-H under RD, and the efficacy and safety were assessed., Results: DLT was grade 3 vomiting at 40 mg/m(2). Therefore, MTD and RD were 35 mg/m(2). The peak of total platinum in plasma was over 1.0 μg/ml at 40 mg/m(2) at 30 min after infusion. Of the 35 patients, 16 (45.7%) demonstrated complete responses, and 4 (11.4%) demonstrated partial responses with an additional 9 patients (25.7%) having stable diseases, as assessed by RECIST. Grade 3 thrombocytopenia was found in 1 patient (2.9%), grade 2 hyperbilirubinemia was found in 2 patients (5.7%), and grade 2 vomiting was found in 4 patients (11.4%)., Conclusion: Lipiodolization using DDP-H at 35 mg/m(2) is effective and well tolerated in patients with unresectable HCC.

Background: Recently, local ablation therapy has been widely used for treatment of small hepatocellular carcinoma (HCC). The present study assessed the outcome of hepatic resection combined with intraoperative local ablation therapy in patients with multinodular HCCs., Methods: Forty-one patients with initial and multinodular HCCs underwent hepatic resection combined with intraoperative local ablation therapy. The mean maximum diameter of all tumors was 3.8 cm (range 2.1-16.0 cm), and the mean number of nodules was 3.2 (range 2-11). We evaluated the survival rates and assessed the prognostic factors associated with overall survival rates using Cox proportional hazard models., Results: Intraoperative local ablation therapy was completed in all patients with no evidence of residual viable tumor on the first postoperative computed tomography (CT) scan. The 3-, 5- and 7-year overall survival rates were 84.3%, 61.2%, and 61.2%, respectively. Patients with preoperative des-gamma carboxyprothrombin (DCP) level >300 mAU/ml showed significantly worse overall survival than those with DCP level 300 mAU/ml was a significant prognostic factor of long-term overall survival.

The occurrence of de novo hepatocellular carcinoma (HCC) after liver transplantation (LT) for advanced HCCs has been extremely limited. In this article, a case of de novo HCC in a liver graft with sustained hepatitis C virus clearance after living donor liver transplantation (LDLT) for multiple HCCs and hepatitis C cirrhosis is reported. The recipient was a 58-year-old female, and the left lobe living donor was the 30-year-old healthy daughter of the recipient. Three years after LDLT, the patient received 48 weeks of interferon treatment for recurrent hepatitis C with advanced fibrosis. The patient has shown successful viral clearance since then. However, an HCC was recognized in the liver graft during a follow-up computed tomography scan performed 6 years after LDLT, and it was surgically resected. To analyze its origin [either from the patient (metastatic) or from the living donor (de novo)], genotyping by microsatellite analysis of tissue and blood samples from the donor and recipient was performed, and it revealed that the HCC originated from the donor. To the best of our knowledge, this is the first report of de novo HCC in a liver graft with sustained hepatitis C virus clearance after LT for advanced HCCs and hepatitis C cirrhosis.

Objective: Microscopic portal vein invasion (PVI) by cancer cells is a poor prognostic factor after hepatic resection for hepatocellular carcinoma (HCC). The aim of this study is to predict PVI preoperatively in patients with HCC., Methods: We studied 46 hepatectomized patients who had HCC without any portal venous invasion detected during preoperative radiographic evaluation. We defined the portal perfusion defect area ratio (PPDAR) as the following: the quotient of the maximal portal perfusion defect area, on computed tomography during arterio-portography (CTAP) is divided by the maximal tumor area on magnetic resonance imaging (MRI) or CT., Results: The median PPDAR was 1.3 (mean 1.4 +/- 1.1; ranged from 0.7 to 5.8). The incidence of PVI was 4.5% in patients with a PPDAR <1.3, 35.7% in those with a PPDAR of 1.3-1.6, 70% in those with a PPDAR > or = 1.6 (P = 0.0005). When analyzing the preoperative value of different cut-off points for the PPDAR, the lowest P-value by Fisher's exact test was achieved when the PPDAR threshold was 1.6 (P = 0.0012). The sensitivity was 58%, and specificity was 91% with this cut-off value. On univariate analyses, factors that significantly correlated with PVI were PPDAR (P = 0.0012), serum levels of des-gamma-carboxy prothrombin (P = 0.033), and tumor size (P = 0.0126). On multivariate analysis, PPDAR was the only significant independent predictor of PVI., Conclusion: Our study shows that PPDAR is a new concept, which is useful in predicting PVI and that a value > or = 1.6 is predictive of PVI.

Background: Intrahepatic cholangiocarcinoma (ICC) is a primary adenocarcinoma of the liver arising from the intrahepatic bile duct. Hepatectomy with extensive lymph node dissection is the standard treatment for ICC., Patients and Methods: Sixty patients with ICC who underwent hepatectomy in our institution between 1986 and 2005 were investigated to determine prognostic factors and to evaluate the impact of surgical treatment for ICC using univariate and multivariate analyses., Results: The overall survival rate of the R0 resection group (n=43) was significantly higher than that of the R1/2 group (n=17). However, in patients with lymph node metastasis (n=24), R0 resection had no survival impact. According to multivariate analysis, the independent factors of poor prognosis were: the presence of lymph node metastasis, lymphatic invasion, poor differentiation and R1/2 resection., Conclusion: R0 resection can provide prolonged survival for patients with ICC. Patients with lymph node metastasis, lymphatic invasion, or poorly differentiated ICC have poor prognosis after operation and additional treatment, such as adjuvant chemotherapy, is recommended.