Takenari Nakata

CONCOMITANT CAUDATE LOBE RESECTION AS AN OPTION FOR DONOR HEPATECTOMY IN ADULT LIVING RELATED LIVER TRANSPLANTATION

In this article, we describe a successful adult living related partial liver transplantation (LRLT) using the left lobe with the left-side caudate lobe (the Spiegel lobe and the left side of the paracaval portion). The size of the donors left lobe was 29% of the recipients standard liver volume and did not seem to meet our criteria for adult-to-adult LRLT. However, the donor had a thick left-side caudate lobe. The estimated volume of the left lobe with the left-side caudate lobe was 32%, which met our criteria for the adult recipient. The recipients CT scan on day 87 after transplantation showed the preserved blood flow and no biliary congestion in the left-side caudate lobe, which suggests maintenance of lobe function. This procedure may be an option for adult-to-adult LRLT in which the donor has a thick left-side caudate lobe.

Predictive factors for intrahepatic cholangiocarcinoma recurrence in the liver following surgery

BackgroundWe performed hepatectomy without lymph node (LN) dissection for intrahepatic cholangiocarcinoma (ICC) limited to the peripheral region of the liver, and hepatectomy with extrahepatic bile duct resection and regional LN dissection for any types of ICC extending to the hepatic hilum. Surgical outcomes were evaluated to elucidate the prognostic factors that influence patient survival with respect to intrahepatic recurrence.MethodsForty-one patients underwent resection of ICC with no macroscopic evidence of residual cancer.ResultsSignificant risk factors for poorer survival included preoperative jaundice (P = 0.0115), serum CA19-9 levels >37 U/ml (P = 0.0089), tumor diameter >4.5 cm (P = 0.017), ICC extending to the hepatic hilum (P = 0.0065), mass-forming with periductal-infiltrating type (P = 0.003), poorly differentiated adenocarcinoma, portal vein involvement (P = 0.0785), LN metastasis at initial hepatectomy (P < 0.0001), and positive surgical margin (P = 0.023). Intrahepatic recurrence, which was the predominant manner of recurrence, was detected in 20 patients (74.1%). Patients with intrahepatic recurrence had a significantly high incidence of high serum CA19-9 levels (>37 U/ml; P = 0.0006), preoperative jaundice (P = 0.0262), ICC extended to the hepatic hilum (P = 0.0349), large tumors (>4.5 cm; P = 0.0351), portal vein involvement (P = 0.0423), and LN metastasis at initial hepatectomy (P = 0.009) compared with disease-free patients. The multiple logistic regression analysis revealed that preoperative CA19-9 elevation and obstructive jaundice influenced intrahepatic recurrence of ICC.ConclusionsAlthough LN metastasis is a significant prognostic factor, the most obvious recurrence pattern after surgery was intrahepatic recurrence, which could be predicted preoperatively by a combination of elevated serum CA19-9 levels and manifestation of obstructive jaundice.

Disease recurrence patterns after R0 resection of hilar cholangiocarcinoma

There is little information regarding the clinical behaviour of hilar cholangiocarcinoma after curative resection.

Prognostic impact of anatomical resection on early and late intrahepatic recurrence in patients with hepatocellular carcinoma

BACKGROUND/PURPOSE Little has been addressed regarding the impact of the type of resection, which can be anatomical or nonanatomical, for patients with hepatocellular carcinoma (HCC), from the viewpoint of early (< or =2-year) and late (>2-year) intrahepatic recurrence. The aim of the present study was to investigate this issue. METHODS Between 1990 and 2004, we performed 365 potentially curative liver resections. Among these, 233 patients with a solitary tumor were the subjects of this study. They were classified into two groups: anatomical resection (n = 106) and nonanatomical resection (n = 127). We evaluated the following outcomes: (1) early and late recurrence rates; (2) topography of the recurrent tumors; and (3) risk factors for early recurrence. RESULTS The early recurrence rate after anatomical resection was significantly lower than that after nonanatomical resection: recurrence rates at 1 and 2 years were 13.8% and 29.8%, respectively, in the former group; while they were 22.6% and 46.3%, respectively, in the latter group (P = 0.01; log-rank test). However, late recurrence rates were similar in the two groups (P = 0.36). Local recurrence was observed in 25 of the 89 patients with intrahepatic recurrence after nonanatomical resection (28%), whereas it was observed in 3 of the 64 patients with intrahepatic recurrence after anatomical resection (5%), showing a significantly lower local recurrence rate in the anatomical resection group (P = 0.0002). Cox multivariate analysis identified the type of resection employed as one of the variables contributing to early HCC recurrence (nonanatomical resection: hazard ratio, 1.84; 95% confidence interval [CI], 1.01-3.37). CONCLUSIONS Anatomical resection would be a more appropriate strategy than nonanatomical resection for preventing early intrahepatic recurrence in patients with solitary HCC. However, the type of resection has no significant influence on late recurrence.

Efficacy of preoperative endoscopic nasobiliary drainage for hilar cholangiocarcinoma

BACKGROUND/PURPOSE Although percutaneous transhepatic biliary drainage has previously been recommended as a primary preoperative step, endoscopic nasobiliary drainage (ENBD) is prevalent as an alternative procedure. Few reports assess the efficacy and safety of ENBD in a substantial patient cohort. METHODS Of 116 patients with hilar cholangiocarcinoma who underwent surgery, 62 (43 men and 19 women, median age 69 years) underwent preoperative ENBD. After classification of lesions according to Bismuth-Corlette (B-C) criteria, we evaluated efficacy and safety with respect to B-C type. RESULTS Patients were classified as B-C types I (n = 5), II (n = 21), IIIa (n = 23), IIIb (n = 5), and IV (n = 8). Preoperative single ENBD was effective in 46/62 patients (74%) including 5/5 (100%) B-C type I, 20/21 (94%) type II, 16/23 (70%) type IIIa, 4/5 (80%) type IIIb, and 1/8 (13%) type IV. Sixteen cases (26%) required additional drainages with ENBD or endoscopic biliary stenting (EBS) in 8/16 (50%), and with PTBD in 8/16 (50%). Mild acute pancreatitis (n = 1, 2%), segmental cholangitis (n = 2, 3%), and acute cholangitis with catheter obstruction (n = 7, 11%) occurred with ENBD. CONCLUSIONS Preoperative single ENBD in the future remnant lobe is effective treatment for B-C type I-III hilar cholangiocarcinoma. Preoperative ENBD was rarely complicated with segmental cholangitis.

Primary Liver Carcinoma Exhibiting Dual Hepatocellular-Biliary Epithelial Differentiations Associated With Citrin Deficiency : A Case Report

We report a 50-year-old male patient with primary liver carcinoma exhibiting dual hepatocellular and biliary epithelial differentiations associated with citrin deficiency (asymptomatic adult-onset type II citrullinemia, CTLN2). Although so far 14 CTLN2 patients with hepatocellular carcinoma have been reported, this report describes a unique case of liver carcinoma showing the features of both hepatocellular and cholangiocellular carcinoma. In addition to the clinical data of the 14 patients reported previously, the findings in our patient suggest that the citrin deficiency might be one of the key disorders causing hepatocellular carcinoma especially at younger ages and can also play an important role in hepatocarcinogenesis of the hepatic progenitor cells, which have the bipotential to differentiate into both hepatocytes and cholangiocytes.

Clinical and pathological features of primary carcinoma of the cystic duct

BACKGROUND According to Farrars criteria, a tumor restricted to the cystic duct is defined as cystic duct carcinoma, but this definition excludes advanced carcinoma originating from the cystic duct. PATIENTS AND METHODS For the purpose of this study, primary cystic duct carcinoma was defined as a tumor originating from the cystic duct. We investigated the clinicopathological features of 15 cystic duct carcinomas, including 13 that did not fit Farrars criteria, and compared them with those of 52 cases of gallbladder carcinoma and 161 cases of extrahepatic bile duct carcinoma. RESULTS The incidence of primary cystic duct carcinoma was 6.6% among all malignant biliary tumors. The main symptom was jaundice in 67% of cases. The operative procedures employed ranged from cholecystectomy to hepatopancreatoduodenectomy. The cases of cystic duct carcinoma and bile duct carcinoma showed a high frequency of perineural infiltration. The overall 5-year survival rate of the 15 patients was 40%. CONCLUSION Patients with advanced cystic duct carcinoma show a high frequency of jaundice and perineural infiltration. Our data suggest that cystic duct carcinoma may be considered a distinct subgroup of gallbladder carcinoma. Radical surgery is necessary for potentially curative resection in patients with advanced cystic duct carcinoma.

Role of bone marrow cells in the development of pancreatic fibrosis in a rat model of pancreatitis induced by a choline-deficient/ethionine-supplemented diet

Bone marrow cell (BMC)-derived myofibroblast-like cells have been reported in various organs, including the pancreas. However, the contribution of these cells to pancreatic fibrosis has not been fully discussed. The present study examined the possible involvement of pancreatic stellate cells (PSCs) originating from BMCs in the development of pancreatic fibrosis in a clinically relevant rat model of acute pancreatitis induced by a choline-deficient/ethionine-supplemented (CDE) diet. BMCs from female transgenic mice ubiquitously expressing green fluorescent protein (GFP) were transplanted into lethally irradiated male rats. Once chimerism was established, acute pancreatitis was induced by a CDE diet. Chronological changes in the number of PSCs originating from the donor BMCs were examined using double immunofluorescence for GFP and markers for PSCs, such as desmin and alpha smooth muscle actin (αSMA), 1, 3 and 8 weeks after the initiation of CDE feeding. We also used immunohistochemical staining to evaluate whether the PSCs from the BMCs produce growth factors, such as platelet-derived growth factor (PDGF) and transforming growth factor (TGF) β1. The percentage of BMC-derived activated PSCs increased significantly, peaking after 1 week of CDE treatment (accounting for 23.3±0.9% of the total population of activated PSCs) and then decreasing. These cells produced both PDGF and TGFβ1 during the early stage of pancreatic fibrosis. Our results suggest that PSCs originating from BMCs contribute mainly to the early stage of pancreatic injury, at least in part, by producing growth factors in a rat CDE diet-induced pancreatitis model.

Isolation and characterization of portal branch ligation-stimulated Hmga2-positive bipotent hepatic progenitor cells.

Hepatic stem/progenitor cells are one of several cell sources that show promise for restoration of liver mass and function. Although hepatic progenitor cells (HPCs), including oval cells, are induced by administration of certain hepatotoxins in experimental animals, such a strategy would be inappropriate in a clinical setting. Here, we investigated the possibility of isolating HPCs in a portal branch-ligated liver model without administration of any chemical agents. A non-parenchymal cell fraction was prepared from the portal branch-ligated or non-ligated lobe, and seeded onto plates coated with laminin. Most of the cells died, but a small number were able to proliferate. These proliferating cells were cloned as portal branch ligation-stimulated hepatic cells (PBLHCs) by the limiting dilution method. The PBLHCs expressed cytokeratin19, albumin, and Hmga2. The PBLHCs exhibited metabolic functions such as detoxification of ammonium ions and synthesis of urea on Matrigel-coated plates in the presence of oncostatin M. In Matrigel mixed with type I collagen, the PBLHCs became rearranged into cystic and tubular structures. Immunohistochemical staining demonstrated the presence of Hmga2-positive cells around the interlobular bile ducts in the portal branch-ligated liver lobes. In conclusion, successful isolation of bipotent hepatic progenitor cell clones, PBLHCs, from the portal branch-ligated liver lobes of mice provides the possibility of future clinical application of portal vein ligation to induce hepatic progenitor cells.

Hepatectomy preserving drainage veins of the posterior section for liver malignancy invading the right hepatic vein: an alternative to right hepatectomy.

BACKGROUND Although a right hepatectomy (RH) traditionally has been performed for liver tumors infiltrating the main trunk of the right hepatic vein (RHV), the presence of drainage veins of the posterior section (DVPS) beside the RHV provides a chance to preserve their draining area even if the main trunk of the RHV is removed. METHODS Since 2005, we systematically have performed DVPS-preserving hepatectomies whenever possible. In the present study, we describe our experience treating 12 consecutive patients who underwent this procedure. RESULTS We performed the following types of liver resections concomitant with the main trunk of the RHV without packed red cell transfusion, liver failure, or 90-day mortality: extended right anterior sectionectomy in 2 patients, extended segmentectomy 7 in 3, extended segmentectomy 8 in 2, and partial resection of segment 7 in 2 and segment 8 in 3. Postoperative morbidity was observed in 4 (33%) cases, all of which had pleural effusion requiring a tap. A free resection margin was obtained in all patients. CONCLUSIONS This procedure could be a useful alternative to RH, providing a chance for radical liver resection with minimal parenchymal sacrifice in selected patients with DVPS.