Susumu Eguchi

Comparison of the outcomes between an anatomical subsegmentectomy and a non-anatomical minor hepatectomy for single hepatocellular carcinomas based on a Japanese nationwide survey.

BACKGROUND Although a surgical resection is an important modality for the treatment of hepatocellular carcinoma (HCC), the impact of the operative method on both the patient survival and disease-free survival (DFS) still remains controversial. METHODS Using a nationwide Japanese database, 72,744 patients with HCC who underwent a curative liver resection between 1994 and 2001 were divided into two groups based on whether an anatomical subsegmentectomy (AS) or a non-anatomical minor hepatectomy (MH) was performed. A total of 5,781 patients with single HCCs were selected for the study and divided into 3 subgroups based on the size of the HCCs (less than 2 cm, 2 to 5 cm, and greater than 5 cm in diameter). An AS was performed for 2,267 patients while an MH was performed for 3,514 patients. RESULTS The overall DFS was significantly better after an AS (P = .0089). When the patients were stratified according to the size of the HCC, a better DFS was seen in the patients with HCC from 2 to 5 cm after an AS (P < .0005). Further stratification according to liver damage did not show any significant differences between an AS and an MH. CONCLUSION An AS is therefore recommended, especially when the size of HCC ranges from 2 to 5 cm.

Mutations of the p53 gene in the stool of patients with resectable colorectal cancer

This study was undertaken to evaluate whether genetic analysis in the stool can be useful for detecting malignant tumors in the colon and rectum. We searched for the possible presence of mutations in the p53 gene in the stool of patients with resectable colorectal cancer. Alterations in the p53 gene are the most frequent among mutant genes related to colorectal cancer.

Perioperative synbiotic treatment to prevent infectious complications in patients after elective living donor liver transplantation: a prospective randomized study

BACKGROUND Although the effect of synbiotic therapy using prebiotics and probiotics has been reported in hepatobiliary surgery, there are no reports of the effect on elective living-donor liver transplantation (LDLT). METHODS Fifty adult patients undergoing LDLT between September 2005 and June 2009 were randomized into a group receiving 2 days of preoperative and 2 weeks of postoperative synbiotic therapy (Bifidobacterium breve, Lactobacillus casei, and galactooligosaccharides [the BLO group]) and a group without synbiotic therapy (the control group). Postoperative infectious complications were recorded as well as fecal microflora before and after LDLT in each group. RESULTS Only 1 systemic infection occurred in the BLO group (4%), whereas the control group showed 6 infectious complications (24%), with 3 cases of sepsis and 3 urinary tract infections with Enterococcus spp (P = .033 vs BLO group). No other type of complication showed any difference between the groups. CONCLUSIONS Infectious complications after elective LDLT significantly decreased with the perioperative administration of synbiotic therapy.

Recurrence‐free survival more than 10 years after liver resection for hepatocellular carcinoma

High recurrence rates after liver resection with curative intent for hepatocellular carcinoma (HCC) remain a problem. The characterization of long‐term survivors without recurrence after liver resection may help improve the therapeutic strategy for HCC.

Differential effects of calcineurin inhibitors, tacrolimus and cyclosporin a, on interferon-induced antiviral protein in human hepatocyte cells†

The premise of our study is that selective inhibition of interferon (IFN) by calcineurin inhibitors contribute to the increased severity of hepatitis C virus (HCV) posttransplantation. Therefore, we examined the influence of calcineurin inhibitors in the human hepatocyte cell line on IFN‐α‐induced phosphorylation of Janus kinase (Jak) and signal transducers and activators of transcription (STAT), nuclear translocation of IFN‐stimulated gene factor 3 (ISGF‐3), IFN‐stimulated regulatory element (ISRE)‐contained promoter activity, and the expressions of antiviral proteins. Tacrolimus (Tac), but not cyclosporin A (CyA), had an inhibitory effect on IFN‐α‐induced double‐stranded ribonucleic acid (RNA)‐dependent protein kinase (PKR) in a dose‐dependent manner. STAT‐1 also acted in a similar fashion to PKR. IFN‐α combined with Tac attenuated the ISRE‐containing promoter gene activity as compared with IFN‐α alone. In contrast, its expression in pretreated CyA was slightly attenuated. In pretreated Tac, but not CyA, the levels of IFN‐α‐induced tyrosine phosphorylated STAT‐1 and ‐2 were clearly lower than those induced by IFN‐α alone. Tac and CyA did not decrease the IFN‐α‐induced JAK‐1 phosphorylation. The nuclear translocation rate of tyrosine phosphorylated STAT‐1 was inhibited by pretreatment of both Tac and CyA by western blotting and immunohistochemistry. In an HCV replicon system, pretreated Tac diminished the replication inhibitory effect of IFN‐α. In this study, we show that calcineurin inhibitors, especially Tac, are the negative regulators of IFN signaling in the hepatocyte; the greatest cause of such inhibition is the phosphorylation disturbance of STAT‐1, next to inhibition of the nuclear translocation of STAT‐1. In conclusion, disturbance of tyrosine phosphorylation of STAT‐1 resulted in diminished ISRE‐containing promoter activity and a decline in antiviral protein expression. Moreover, the replication of HCV was activated. This phenomenon is detrimental to IFN therapy after liver transplantation, and the selection of calcineurin inhibitors may warrant further discussion depending on the transplant situation. Liver Transpl 14:292–298, 2008.

Evolution of living donor liver transplantation over 10 years: experience of a single center.

PurposeTo evaluate the changes in living donor liver transplantations (LDLTs) over the last 10 years, we analyzed our experience of performing LDLT in a single center.MethodsWe performed 73 LDLTs over the 10 years between 1997 and 2007 in Nagasaki University Hospital, Japan.ResultsInitially, from 1997 to 2003, LDLT was performed for pediatric patients; then, between 2004 and 2007, adult-to-adult LDLT was introduced, primarily for hepatocellular carcinoma (HCC) in liver cirrhosis. We also began performing LDLTs for adults with ABO-incompatible blood type combination in the latter period. As the number of adult-to-adult LDLTs increased, left-sided grafts became fi rst choice for these patients. Survival rates were 88.3%, 77.2%, 70.2% at 1, 3, and 5 years, respectively. There was a relatively low incidence of arterial complications, and although the incidence of biliary complications was high initially, it decreased with experience. Likewise, the operative time, blood loss, and hospital stay after LDLT also improved remarkably.ConclusionOver the last 10 years the indications for, and operative techniques used in LDLT have changed dramatically, even in a single center in Japan.

Fetal rat hepatocytes: isolation, characterization, and transplantation in the Nagase analbuminemic rats.

BACKGROUND In contrast to adult hepatocytes, fetal hepatocytes (FH) are thought to be highly proliferative, less immunogenic, and resistant to cryopreservation and ischemic injury. These qualities could enhance FH engraftment, proliferation, and gene transfer requiring active DNA synthesis. METHODS Rat FH were obtained using the nonperfusion collagenase/DNase digestion method. Free and cultured cells were studied using electron microscopy, fluorescence-activated cell sorting, and Northern analysis using alpha-fetoprotein and albumin as markers of hepatocyte lineage. DNA synthetic activity was measured in quiescent and mitogen-stimulated fetal and adult hepatocytes by [3H]thymidine incorporation. Susceptibility of cultured FH to retrovirally mediated gene transfer was studied using an amphotropic retroviral vector carrying the Escherichia coli lac-Z gene. Nagase analbuminemic rats were used as recipients to study the effects of intraportal FH transplantation. Analysis of serum albumin was carried out by enzyme-linked immunosorbent assay. RESULTS In fetal liver, 87+/-2% of the cells showed morphological and molecular features of hepatocytes. DNA synthetic activity in nonstimulated cultured FH was 10 times greater than the maximal hepatocyte growth factor-driven response in adult rat hepatocytes. A total of 5-15% FH stained positive for X-gal; results of transduction in adult hepatocyte cultures were negative. In Nagase analbuminemic rat recipients, FH produced significant amounts of albumin only when a hepatic regenerative stimulus was applied. Immunohistochemistry confirmed presence of albumin-positive hepatocytes. CONCLUSIONS Fetal rat liver from the late gestation period is highly enriched with hepatocyte progenitors. They are highly proliferative and susceptible to retroviral transduction and can engraft and function in the adult rat liver if transplanted under a hepatic regenerative stimulus.

Significance of hepatitis B virus core‐related antigen and covalently closed circular DNA levels as markers of hepatitis B virus re‐infection after liver transplantation

Currently, hepatitis B virus (HBV) re‐infection after liver transplantation (LT) can be almost completely suppressed by the administration of HBV reverse transcriptase inhibitors and hepatitis B immunoglobulins. However, after transplantation, there is no indicator of HBV replication because tests for the serum hepatitis B surface antigen and HBV‐DNA are both negative. Therefore, the criteria for reducing and discontinuing these precautions are unclear. In this study, we examined the serum HBV core‐related antigen (HBcrAg) and intrahepatic covalently closed circular DNA (cccDNA) in order to determine if these could be useful markers for HBV re‐infection.

The risk factors and predictive factors for anastomotic leakage after resection for colorectal cancer: reappraisal of the literature

Anastomotic leakage is a serious complication that can occur after colorectal surgery. Several risk factors for anastomotic leakage have been reported based on the findings of prospective and retrospective studies, including patient characteristics, the use of neoadjuvant therapy, the tumor location, intraoperative events, etc. However, as these risk factors affect each other, the statistical results have differed in each study. In addition, differences in surgical methods, including laparoscopy versus laparotomy or stapling anastomosis versus handsewn anastomosis, may influence the incidence of anastomotic leakage. This mini-review summarizes the results of reported papers to clarify the current evidence of risk factors for anastomotic leakage.

[d-Ala2, d-Leu5] enkephalin (DADLE) protects liver against ischemia-reperfusion injury in the rat

BACKGROUND [D-Ala(2), D-Leu(5)] enkephalin (DADLE) is a synthetic delta class of opioid and is reported to induce hibernation as well as hibernation induction trigger (HIT) in the serum of hibernating mammals. DADLE and HIT have been demonstrated to protect the heart, lung, and jejunum against ischemia-reperfusion (I-R) injury. In the present study, we examined the effect of DADLE on I-R injury of the liver in rats. METHODS After administration of DADLE (DADLE group) or normal saline as a vehicle (Control group), partial hepatic ischemia was induced by occluding the vessels supplying 92% of the liver for 45 min, followed by declamping the vessels and resection of the non-ischemic lobe. After 120 min of reperfusion, serum glutamic-pyruvic transaminase (GPT), hyaluronic acid (HA) levels, and concentrations of malondialdehyde (MDA) of the liver tissue were measured. Additionally, bile output from the ischemic lobes was measured after reperfusion. RESULTS GPT levels were significantly lower in the DADLE group as compared to those of the Control group (P < 0.05), but the serum levels of HA were not different between the two groups. The concentrations of MDA of the liver tissue were significantly lower in the DADLE group than in the Control group (P < 0.01). The bile output after reperfusion was not significantly different between the two groups. CONCLUSIONS DADLE protects against I-R injury in hepatocytes, but not in the sinusoidal endothelial cells of the liver in rats. An anti-oxidative effect is suggested to be responsible for this effect.