Koichi Kimura

New scoring system for prediction of microvascular invasion in patients with hepatocellular carcinoma

The microvascular invasion of cancer cells (mvi) is a good prognostic factor after hepatic resection (HR) and liver transplantation for hepatocellular carcinoma (HCC). This study aimed to predict mvi in patients with HCC.

The causes, risk factors, and outcomes of early relaparotomy after living-donor liver transplantation

Background Although early relaparotomy of the recipient after living-donor liver transplantation (LDLT) is a significant event, its causes, risk factors, and outcomes are still unclear. Methods A retrospective analysis of 284 cases of adult-to-adult LDLT was performed. Results The incidence of early relaparotomy of the recipient was 9.2% (n=26). The reasons for relaparotomy were divided into three groups: postoperative bleeding (n=11, 42.3%), insufficient portal venous flow (n=5, 19.2%), and other (n=10, 38.5%). The 6-month graft survival rates of patients in the early laparotomy and nonlaparotomy groups were 61.5% and 88.4%, respectively (P<0.0001). Patients with postoperative bleeding experienced a significantly higher mortality rate (54.6%) than those with other reasons for early relaparotomy (13.3%; P=0.0231). Multivariate analysis showed that a model for end-stage liver disease score of greater than 20 (odds ratio [OR], 9.06; P=0.0434) and an operative blood loss of greater than 15 L (OR, 9.06; P=0.0434) were significant risk factors for graft loss after early relaparotomy. In patients with patent major shunt vessels (>1 cm in diameter, n=31), portal venous flow of less than 1.0 L/min at the end of surgery was a significant risk factor for early relaparotomy to ligate the remaining shunt vessels (OR, 50.5; P=0.0188). Conclusions Early relaparotomy of the recipient is significantly associated with poor graft survival after LDLT. Massive intraoperative blood loss and high model for end-stage liver disease score were associated with poor graft survival in the relaparotomy group.

Selection of a right posterior sector graft for living donor liver transplantation

Right posterior sector (RPS) grafts have been used to overcome graft size discrepancies, the major concern of living donor liver transplantation. Previous studies have reported the volumetry‐based selection of RPS grafts without anatomical exclusion. We reviewed our data and established selection criteria for RPS grafts. The procurement of RPS grafts [conventional (n = 3) and extended (n = 5)] was performed for 8 of 429 recipients at our center. Extended RPS grafts contained the drainage area of the right hepatic vein. The mean graft weight (GW) according to 3‐dimensional computed tomography volumetry was 488 g, and the GW/standard liver weight (SLW) ratio was 42.6%. The mean actual GW was 437 g, and the GW/SLW ratio was 38.4%. One donor exhibited standard bifurcation of the right portal vein (PV) and the left PV, and 2 donors exhibited trifurcation of the left PV, the right anterior portal vein (APV), and the posterior PV. The remaining 5 donors exhibited APV branching from the left PV, which is the most suitable anatomy for RPS grafts. Two recipients died of sepsis or small‐for‐size graft syndrome. One underwent retransplantation because of an intractable bile leak and fibrosing cholestatic hepatitis. Intractable bile duct (BD) stenosis developed in 4 of the 6 survivors. In conclusion, with the significant complications and potential concerns associated with RPS grafts, these grafts should be used very rarely and with extreme caution. Donors with the standard bifurcation of the PV and the posterior BD running through the dorsal side of the posterior PV are not suitable candidates for RPS grafts. Extended RPS graft procurement is recommended for easier parenchymal transection. Liver Transpl 20:1089–1096, 2014.

Ischemia-Reperfusion Injury in Fatty Liver Is Mediated by Activated NADPH Oxidase 2 in Rats.

Background Liver ischemia-reperfusion (I/R) injury is a severe complication of liver surgery, and steatosis is a risk factor for liver damage. Reactive oxygen species generated by nicotinamide adenine dinucleotide phosphate oxidase (NOX) contribute to liver dysfunction. Here we examined the role of NOX in I/R injury of fatty livers. Methods Rats were fed a methionine and choline-deficient diet to induce a fatty liver. Rats then underwent surgically induced partial hepatic ischemia followed by reperfusion. Results The overall survival rate after I/R was lower in rats with fatty livers than with normal livers (P < 0.01). Necrotic area and the concentrations of 8-hydroxy-2′-deoxyguanosine (8-OHdG), TNF&agr;, and IL-6 were higher in fatty liver tissue than in normal liver tissue (P < 0.01). The number of p47phox-positive cells was significantly higher in fatty liver tissue than in normal liver tissue after reperfusion and peaked 24 hours after reperfusion. The number of TLR-4 positive cells was significantly higher in fatty liver tissue than in normal liver tissue after reperfusion and peaked 4 and 24 hours after reperfusion coupled with a decreased number of high-mobility group box 1–positive hepatocytes. Apocynin significantly improved the survival rate, necrotic area, and concentrations of 8-hydroxy-2′-deoxyguanosine, TNF&agr;, and IL-6 (P < 0.01). The protective effect of apocynin on fatty livers was greater than on normal livers. Conclusions Ischemia-reperfusion injury was associated with increased high-mobility group box 1, TLR4, and NOX2. Inhibition of NOX activity improved oxidative stress and may prevent I/R injury in fatty liver.

Correlation Between Portal Vein Anatomy and Bile Duct Variation in 407 Living Liver Donors

Our aim was to determine whether variant bile duct (BD) anatomy is associated with portal vein (PV) and/or hepatic artery (HA) anatomy. We examined the associations between BD anatomy and PV and/or HA anatomy in 407 living donor transplantation donors. We also examined whether the right posterior BD (RPBD) course was associated with the PV and/or HA anatomy. Variant PV, HA and BD anatomies were found in 11%, 25% and 25%, respectively, of 407 donors enrolled in this study. The presence of a variant BD was more frequently associated with a variant PV than with a normal PV (61% vs. 20%, p < 0.0001). By contrast, the presence of a variant HA was not associated with a variant BD. A supraportal RPBD was found in 357 donors (88%) and an infraportal RPBD was found in 50 donors (12%). An infraportal RPBD was significantly more common in donors with a variant PV than in donors with a normal PV (30% vs. 10%, p = 0.0004). Variant PV, but not variant HA, anatomies were frequently associated with variant BD anatomy. Additionally, an infraportal RPBD was more common in donors with a variant PV than in donors with a normal PV.

Clinical significance of gastrointestinal bleeding after living donor liver transplantation

The clinical presentations of gastrointestinal bleeding (GIB) occurring after living donor liver transplantation (LDLT) have not been fully described. We performed a retrospective analysis of 297 LDLT cases. Nineteen patients (6.4%) experienced GIB after LDLT. The etiology of GIB included bleeding at the jejunojejunostomy following hepaticojejunostomy (n = 13), peptic ulcer disease (n = 2), portal hypertensive gastropathy (n = 2), and other causes (n = 2). Hemostasis was achieved in 13 patients (68.4%) by endoscopic (n = 3), surgical (n = 1), or supportive treatments (n = 15), but not in the other six patients. Graft dysfunction (P < 0.001), hepaticojejunostomy (P = 0.01), portal vein pressure at the end of surgery >20 mmHg (P = 0.002), and operative blood loss >10 L (P = 0.004) were risk factors. One‐year graft survival rate was significantly lower in patients with GIB than in patients without GIB (P < 0.001). The inhospital mortality rate was 52.6% for patients with GIB, 75.0% for patients with graft dysfunction, and 14.3% for patients without graft dysfunction (P = 0.028). Despite its infrequency after LDLT, GIB has strong correlation with graft dysfunction and inhospital mortality.

Graft selection strategy in adult‐to‐adult living donor liver transplantation: When both hemiliver grafts meet volumetric criteria

To ensure donor safety in living donor liver transplantation (LDLT), the left and caudate lobe (LL) is the preferred graft choice. However, patient prognosis may still be poor even if graft volume (GV) selection criteria are met. Our aim was to evaluate the effects of right lobe (RL) donation when the LL graft selection criteria are met. Consecutive donors (n = 135) with preoperative LL graft volumetric GV/standard liver volume (SLV) of ≥35% and RL remnant of ≥35% were retrospectively studied. Patients were divided into 2 groups: LL graft and RL graft. Recipients body surface area (BSA), Model for End‐Stage Liver Disease (MELD) score, and the donors age were higher in the RL group. The donors BSA and preoperative volumetric GV/SLV of the LL graft were smaller in the RL group. The predicted score (calculated using data for graft size, donor age, MELD score, and the presence of portosystemic shunt, which correlated well with graft function and with 6‐month graft survival) of the RL group, was significantly lower if the LL graft were used, but using the actual RL graft improved the score equal to that of the LL group. Six‐month and 12‐month graft survival rates did not differ between the 2 groups. In patients with a poor prognosis, a larger RL graft improved the predicted score and survival was equal to that of patients who received LL grafts. In conclusion, graft selection by GV, donor age, and recipient MELD score improves outcomes in LDLT. Liver Transplantation 22 914–922 2016 AASLD

Application of Postoperative Model for End-Stage Liver Disease Scoring System for Evaluating Liver Graft Function After Living Donor Liver Transplantation

BACKGROUND The Model for End-Stage Liver Disease (MELD) score has been validated to predict the mortality rate of patients with various chronic liver diseases on the waiting list for liver transplantation (LT). The aim of this study was to assess the value of the postoperative MELD scoring system as an early postoperative predictor of outcome in patients undergoing living donor LT (LDLT). METHODS A retrospective analysis of 217 adult-to-adult LDLT patients was performed. The values of the MELD score on various postoperative days (PODs) as predictors of graft loss within 6 months after LDLT were examined by calculating the areas under the receiver operating characteristic (AUROC) curves. The 6-months graft survival rates were compared between patients with (n = 22) and without (n = 195) graft loss. Univariate and multivariate analyses were performed to identify the factors associated with mortality. RESULTS The MELD score on POD2 was a predictor of graft loss, with an AUROC c-statistic of 0.779, a specificity of 79.5%, and a sensitivity of 68.2% at optimal cutoff, whereas the preoperative MELD score c-statistic was 0.605 with 44.6% sensitivity. Multivariate analyses for postoperative mortality revealed MELD-POD2 ≥19 (odds ratio, 5.601; 95% confidence interval [CI], 1.395-4.508; P = .0009) as an independent predictor of short-term graft loss following LDLT, in addition to preoperative hospitalization status. Later MELD POD scores were also predictive of graft loss. CONCLUSIONS The early postoperative MELD scoring system is feasible as an index for prediction of postoperative mortality following LDLT.

Functional Remnant Liver Assessment Predicts Liver-Related Morbidity After Hepatic Resection In Patients With Hepatocellular Carcinoma.

We aimed to evaluate whether functional assessment of the future remnant liver is a predictor of postoperative morbidity after hepatic resection in patients with hepatocellular carcinoma (HCC).

Global, cancer-specific microRNA cluster hypomethylation was functionally associated with the development of non-B non-C hepatocellular carcinoma

BackgroundWhile hepatitis B and C viral infection have been suppressed, non-B non-C hepatocellular carcinoma (NBNC-HCC) is considered to be rising in incidence terms in some developed countries where prevalence of those viral infections among HCC patients had been very high (such as Japan, Korea, and Italy). To elucidate critical molecular changes in NBNC-HCC, we integrated three large datasets relating to comprehensive array-based analysis of genome-wide DNA methylation (N = 43 pairs) and mRNA/miRNA expression (N = 15, and 24 pairs, respectively) via statistical modeling.ResultsHierarchical clustering of DNA methylation in miRNA coding regions clearly distinguished NBNC-HCC tissue samples from relevant background tissues, revealing a remarkable tumor-specific hypomethylation cluster. In addition, miRNA clusters were extremely hypomethylated in tumor samples (median methylation change for non-clustered miRNAs: -2.3%, clustered miRNAs: -24.6%). The proportion of CpGs hypomethylated in more than 90% of the samples was 55.9% of all CpGs within miRNA clusters, and the peak methylation level was drastically shifted from 84% to 39%. Following statistical adjustment, the difference in methylation levels within miRNA coding regions was positively associated with their expression change. Receiver operating characteristic (ROC) analysis revealed a great discriminatory ability in respect to cluster-miRNA methylation. Moreover, miRNA methylation change was negatively correlated with corresponding target gene expression amongst conserved and highly matched miRNA sites.ConclusionsWe observed a drastic negative shift of methylation levels in miRNA cluster regions. Changes in methylation status of miRNAs were more indicative of target gene expression and pathological diagnosis than respective miRNA expression changes, suggesting the importance of genome-wide miRNA methylation for tumor development. Our study dynamically summarized global miRNA hypomethylation and its genome-wide scale consequence in NBNC-HCC.