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This study was carried out to clarify the clinicopathological features of hepatocellular carcinoma (HCC) arising in patients without viral infection and to confirm the influence of metabolic syndrome (MS) on characteristics in HCC patients.Two hundred and thirty-three hepatectomized HCC patients were enrolled. The status of the hepatitis viral infection was defined; non-B non-C (NBNC) (n = 15), negative for HBs-Ag, HBc-Ab or HCV-Ab; HBV (n = 70); HCV (n = 148). We compared clinicopathological features and surgical outcomes among three groups. Additionally, fifty-six HCC patients who were evaluated on coexistence of MS were divided into two groups and analyzed; MS (n = 16) and non-MS (n = 40) groups.In NBNC-patients, preoperative platelet counts and ICGR15 were significantly better compared to HCV-patients (21.8 x 10(4)/mm3 vs. 11.3 x 10(4)/mm3, 14.0% vs. 19.2%, p0.05). Body mass index was significantly higher in NBNC-patients (24.9 vs. 22.4, p0.05). Overall survival rates were significantly higher in NBNC-patients compared with HBV or HCV-patients (5 y: 87.5% vs. 48.8%, 42.9%, p0.05). For NBNC-patients there were significantly more patients in the MS group than in the non-MS group.HCC with MS included more NBNC-HCC than HBV or HCV related HCC. Aggressive hepatectomy contributed to the favorable outcome in NBNC-patients because of their better liver function.

After hepatic resection, delayed flatus and impaired bowel movement often cause problematic postoperative ileus. Kampo medicine, Dai-kenchu-to (DKT), is reported to have a various beneficial effects on bowel systems. The aim of this study was to prospectively evaluate effects of DKT after hepatic resection.Thirty-two patients who underwent hepatic resection between July 2007 and August 2008 in Tokushima University Hospital were prospectively divided into DKT group (n=16) and control group (n=16). In DKT group, 2.5 g of DKT was administered orally three times a day from postoperative day (POD) 1. Blood was examined on POD 1, 3, 5 and 7. Postoperative first flatus, bowel movement and full recovery of oral intake, hospital stays and complications were checked.In DKT group, levels of c-reactive protein and beta-(1-3)-D-glucan on POD 3 were significantly decreased (p0.05). Moreover, postoperative periods for the first flatus, bowel movement and the full recovery of oral intake were significantly shortened in DKT group (p0.05).DKT suppressed inflammatory reaction, stimulated bowel movement and improved oral intake after hepatic resection, which may decrease serious morbidity after hepatic resection.

The impact of pegylated-interferon (PEG-IFN) α-2b on liver regeneration has not yet been elucidated.Rats were divided into the following four groups: 70% hepatectomy (Hx); 70% Hx+PEG-IFN; 90% Hx and 90% Hx+PEG-IFN group (n=6 each). Rats were pretreated with subcutaneous of PEGIFN α-2b (1.5 μg/kg) administration 24 hours before Hx. Samples were taken 24, 48 and 72 hours after Hx and the following parameters were investigated: blood analysis (AST, WBC, PLT); liver weight to body weight ratio (Lw/Bw ratio); survival and PCNA labeling index (LI).In the 90% Hx model, there was no significant difference between the Hx+PEG-IFN group and the Hx alone group in blood analysis; AST after postoperative 24 hours (2511 vs. 2466 IU/L), WBC (1200 vs. 1290) and PLT (107 vs. 111 x 10⁴/mm³), in Lw/Bw ratio at postoperative 0, 24, 48, 72 hours, respectively (0.38, 0.60, 1.14, 1.69 vs. 0.37, 0.64, 1.12, 1.63), in postoperative survival (40% vs. 45%), and in PCNA LI at postoperative 0, 24, 48, 72 hours, respectively (10.4%, 16.8%, 14.6%, 12.8% vs. 10.0%, 17.1%, 15.6%, 13.7%). In the 70% Hx model, there was no significant difference between the Hx+PEG-IFN group and the Hx alone group for all parameters.Our data demonstrated that PEG-IFN α-2b did not affect liver regeneration and the early use of PEG-IFN α-2b would cause no problems after liver transplantation using partial grafts including living donor liver transplantation.

Background/aims Intrahepatic cholangiocarcinoma (IHCC) is known to be one of the most malignant tumors. Hypoxia-inducible factor-1 (HIF-1) is a transcription factor, which plays a central role in biologic processes under hypoxic conditions. The aim of this study was to elucidate the role of HIF-1 in IHCC. Methodology Thirty-five patients with IHCC who underwent hepatic resection were enrolled in this study. The expression of HIF-1a was determined immunohistochemically and the patients were divided into two groups: HIF-1a positive group (n=22) and HIF-1a negative group (n=13). Clinicopathological variables including prognosis were compared between the two groups. The prognostic factors were investigated by multivariate analysis using Cox's proportional hazard model. Results HIF-1a expression correlated significantly with higher stage, and tended to correlate with tumor diameter (>4cm), vessels infiltration and intrahepatic metastasis. The prognosis in HIF-1a positive group was poorer than that in HIF-1a negative group (5-year survival: 62.9% vs. 18.3%). Furthermore, HIF-1a positive expression was identified as an independent prognostic factor for both overall and disease free survival. Conclusions The findings suggested that the intratumoral HIF-1a regulated malignant behavior and was a new prognostic indicator of IHCC.

Selenoprotein P (SeP), a plasma protein, is considered to have a protective effect against various organ damages. We investigated whether addition of SeP to storage solution could attenuate cold ischemia/reperfusion injury (IRI) in rat liver transplantation.After 24 hrs cold preservation in either University of Wisconsin (UW) solution with or without SeP (1 micromol/L or 10 micromol/L), the liver was flushed with warm lactated Ringer's solution. Alanine aminotransferase (ALT) level in the venous effluent was measured. Orthotopic liver transplantation (OLTx) was then performed after the same preservation as above. Blood biochemical features and tissue lipid peroxide levels were measured after OLTx, and morphometric changes analyzed by hematoxylin and eosin, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) staining.ALT levels in effluent in the SeP 10 group were significantly lower than those in other groups. Serum aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were significantly decreased in the SeP 10 group. Histological examinations showed amelioration of sinusoidal damage in the SeP 10 group at 1 hr after OLTx. Percentages of necrotic areas and apoptotic sinusoidal endothelial cells were decreased in the SeP 10 group.The addition of SeP to UW solution attenuates injury in OLTx.

A clinicopathological analysis of a case with long-term survival after surgical resection for hepatocellular carcinoma (HCC) with massive bile duct tumor thrombus (BDTT) is presented. A 73-year-old female, who was hepatitis C antibody-positive, was referred to our hospital for jaundice. She had a history of small HCC in segment 4 of the liver, which was treated by percutaneous ethanol injection therapy 5 years previously. Contrast-enhanced magnetic resonance imaging detected the primary tumor in segment 4, and a BDTT in the common bile duct with dilatation of the intrahepatic bile duct. Percutaneous transhepatic cholangiography revealed a defect from the bilateral hepatic ducts to the middle part of the common bile duct. Left lobectomy of the liver with thrombectomy and local bile duct resection was performed. The patient has remained alive with no sign of recurrence for 5 years since the surgery. Here, we describe this case of HCC with BDTT showing long-term survival and the usefulness of curative surgical resection with removal of the tumor thrombus.

The postoperative survival rate is dependent on the invasive depth of the gallbladder carcinoma. When this carcinoma has invaded beyond the subserosal layer, lymph node and adjacent organ involvement is found in a large number of patients, and long-term survival cannot be achieved. The aim of this study is to establish a surgical strategy for advanced gallbladder carcinoma according to the invasive depth.A retrospective analysis was conducted of 44 patients with the gallblader carcinoma. The invasive depth was histologically defined by the Japanese Society of Biliary Surgery system as follows. (hinf0: within muscle layer, hinf1a: subserosal layer, hinf1b: hepatic infiltration within 5 mm, hinf2.3: hepatic infiltration more than 5 mm)Wedge resection of the gallbladder bed was performed in 5 cases, and in four of the five patients (80%), intrahepatic recurrence occurred within 6 months. S4a+S5 subsegmentectomy of the liver is performed in 11 cases (hinf0,1a/b:n=5, hinf2,3:n=6) and the postoperative survival rate was significantly better in cases of hinf0,1a/b (p0.05). In cases of hinf2,3 an extended hepatic lobectomy (n=5) tended to obtain a better survival rate, compared with S4a+S5 subsegmentectomy (n=6)(p=0.13).S4a+S5 subsegmentectomy of the liver is a standard operation for GB carcinoma with subserosal invasion.

Despite an adequate hepatic resection, theprognosis of the patients with hepatocellular carcinoma (HCC) that have macroscopic tumor thrombus in the portal vein has still been poor. The prognosis of those patients and was investigated the significance of postoperative adjuvant therapy was discussed in this study.Twenty five patients who had Vp2 or more portal invasion were included in this study. Those patients were retrospectively divided into 2 groups: the systemic interferon alpha, 5-Fluorouracil (FU) and cisplatin group (n = 10, IFN+ chemo group); and the no adjuvant therapy group (n = 15, control group).The overall survival rate was significantly higher in the IFN+chemo group compared with the control group. There was no significant difference between the 2 groups in regard to the disease-free survival rate. However, a difference in the recurrence pattern was observed between the 2 groups. In the IFN+chemo group, 3 of 6 patients with a recurrence had a single tumor in the remnant liver. While in the control group, 10 of 11 recurrent patients had either distant metastasis or multiple recurrences in the residual liver.Our new adjuvant systemic therapy including interferon alpha, 5FU and cisplatin for advanced HCC with macroscopic portal invasion is promising.

Pulse dye densitometry (PDD) using indocyanine-green (ICG) is a newly developed technique for monitoring cardiac output (CO), cardiac index (CI), circulating blood volume (BV) and ICG elimination rate (K-ICG). We measured hemodynamic changes during the perioperative period in patients undergoing digestive surgery to analyze relationships between hemodynamic changes and surgical procedures, blood loss, water balance and SIRS.Eighty-seven patients who underwent gastrectomy (n=46) and colectomy (n=41) without postoperative complications were enrolled in this study. The corresponding data from 15 patients who underwent laparoscopic cholecystectomy were used as controls. CO, CI, BV and K-ICG were measured by PDD before operation, on the first postoperative day (POD 1), POD 3, POD 7 and POD 14.In all patients, CO and CI increased significantly until POD 3 compared with preoperative levels. BV on POD 1 decreased significantly compared to the preoperative level. K-ICG increased significantly until POD 14. Laparoscopic cholecystectomy resulted in less surgical stress than gastrectomy or colectomy as measured by hemodynamic changes. There were minimal differences in hemodynamics between the gastrectomy and colectomy groups. There were significant negative correlations between intraoperative blood loss and the [POD 1: preoperative values] ratios for CO, CI, BV or K-ICG. There was no correlation between changes in water balance from operation to POD 1 and [POD 1: preoperative value] BV ratio.An increase in CO and decrease in BV were observed at the early operative stage, especially in patients with systemic inflammatory response syndrome (SIRS). Interestingly, hepatic artery flow volume (K-ICG) remained high until POD 14. It is important to minimize intraoperative blood loss, since it markedly affects postoperative hemodynamics.

Accurate monitoring of fluid balance in patients after surgery is a difficult task. Bioelectrical impedance analysis (BIA) is a safe and noninvasive method to measure extracellular water (ECW) and intracellular water (ICW) by passing a weak alternating current through the body. The purpose of the present study was to evaluate changes in body water compartments after gastroenterological surgery by BIA in relation to patient age, type of operation, postoperative complications and systemic inflammatory response syndrome (SIRS).Ninety-four patients undergoing digestive surgery in our department [laparoscopic cholecystectomy (n=9), gastrectomy (n= 23), colectomy (n=26), hepatectomy (n=29), pancreatoduodenectomy (n=4) and esophagectomy (n=3)] were enrolled in the study. Body fluids were measured by bioelectrical impedance analysis before and after surgery (one hour after operation and on postoperative days 1, 3, 7 and 14).Total body water (TBW) and ICW in all groups were significantly lower than preoperative values on day 14. Day 14 ECW in patients less than 70 years or age without postoperative SIRS or complications was significantly lower than the preoperative value. In contrast, ECW was not significantly different from the preoperative value in patients older than age 70 with postoperative SIRS. Additionally, ECW on day 14 was significantly higher than the preoperative value in patients with postoperative complications. When types of surgery were taken into consideration, day 14 TBW was significantly lower than preoperative value only in patients with gastrectomy and hepatectomy.Development of postoperative SIRS and complications resulted in an increase of ECW above its preoperative value. BIA is useful for detecting small changes in body composition following gastroenterological surgery, and provides a means for monitoring perioperative water balance.

Activin A is an autocrine inhibitor of cell growth in the liver. The biological activity of activin A is mediated by a heteromeric receptor complex. Follistatin (FS) binds to activin and inhibits its biological effects, and acts as a negative regulator of muscle cells. The role of activin receptors during liver regeneration following a hepatectomy has not been fully assessed. This study investigates the mechanism underlying how activin receptors regulate hepatocyte growth, and the effects of intravenous administration of FS during liver regeneration.The expression of both activins and activin receptors in the liver after a 70% partial hepatectomy (HT) was assessed by RT-PCR and immunohistochemistry. FS 315 or 288 was infused for different periods of time based on changes in hepatocyte activin receptor expression after HT.Activin receptor expression peaked between 48 and 72 hours after HT. 72 hours after HT, an injection of FS 315 resulted in a more potent stimulation of DNA synthesis and produced a greater increase in body weight compared with the control rats.The expression of activin receptors after peak DNA synthesis might be a key component in the downregulation of DNA synthesis. Intravenous administration of FS 315 might promote liver regeneration and have anabolic actions.

We report two cases that underwent extended left hepatic lobectomy combined with resection of the caudate lobe and extrahepatic bile duct only from the left side approach for hilar cholangiocarcinoma. The first case was a 54-year-old man and the second one was a 63-year-old man. Both patients had hilar cholangiocarcinoma with predominant left hepatic duct involvement and required resection and reconstruction of the right hepatic artery as well as left hepatic lobectomy. In both cases, the right hepatic lobe was never mobilized to protect the mechanical damage in the remnant liver and keep co-lateral blood supply route to the remnant liver from the diaphragm or retroperitoneum. Although arterial blood flow to the remnant right hepatic lobe was unfortunately insufficient after reconstruction of the right hepatic artery, the postoperative course was uneventful. The postoperative angiography showed co-lateral arterial blood supply to the right lobe via the subdiaphragmatic artery. In case of extended left hepatic lobectomy combined with resection of the caudate lobe and right hepatic artery, ipsilateral approach (approach only from the left side) is recommended.

Preoperative right portal vein embolization enhances remnant liver function following massive hepatectomy. Several studies have reported an increase in the volume of the left hepatic lobe after right portal vein embolization, but little information exists regarding heat shock protein induction in hepatocytes after right portal vein embolization. The objective of this study is to determine whether heat shock protein is induced in hepatocytes after right portal vein embolization in patients who underwent extended right hepatic lobectomy.Four patients with gallbladder cancer and one patient with intrahepatic cholangiocellular carcinoma who underwent extended right hepatic lobectomy combined with caudate lobectomy and resection of the extrahepatic bile duct after right portal vein embolization were enrolled in this study. Operation was performed 21-36 days after right portal vein embolization. At operation, small liver specimens were taken immediately after laparotomy from both the right anterior segment (embolized lobe) and lower part of the left medial segment (non-embolized lobe) and heat shock protein 70 was induction in these specimens was measured by Western blotting.Heat shock protein 70 was induced in the left lobe relative to the right lobe in four patients, three of whom had an uneventful postoperative course.This paper is the first report to show the induction of heat shock protein 70 in the non-embolized hepatic lobe after right portal vein embolization in the clinical cases.