Masayoshi Nagahama

Characteristics of Hepatocellular Carcinoma in Patients with Negative Virus Markers: Clinicopathologic Study of Resected Tumors

n= 11), hepatitis C virus antibody positive (HC, n= 21), and non-BC (both HbsAg and HCVAb negative, n= 12). Seven patients were excluded from the study because of operative death (n= 3), a history of alcohol abuse (n= 3), or the presence of dual positive HB and HC virus markers (n= 1). The data were analyzed by either an analysis of variance (ANOVA) or a contingency table. The age of the non-BC patients was higher (63.0 ± 4.1, ± SE) than that of HB patients (54.0 ± 3.2, p < 0.05) but was identical to that of the HC group (62.0 ± 1.8). Among the preoperative laboratory data, the serum glutamic oxaloacetate and glutamate pyruvate transaminoses (GOT, GPT) levels were statistically lower in the non-BC patients (32.8 ± 4.8 and 28.0 ± 4.4 IU/L, respectively) than in the HB and HC patients. The pathologic features of the resected specimens in the non-BC patients showed more invasive growth than in specimens from the HB or HC patients. The clinical stages (defined based on the criteria of the Japanese Association of Hepatocellular Carcinoma) were also more advanced in the non-BC patients than in the other groups. Postoperative survival time showed no significant difference among the groups. In conclusion, the non-BC patients had comparatively greater invasive growth and more advanced clinical stages than the HB and HC patients, despite the absence of liver cirrhosis, and so demonstrated the same poor survival data as observed in the HB and HC patients.

Improved hepatic microcirculation by human soluble urinary thrombomodulin in the xeno-perfused porcine liver

Purpose. Both the protein C/thrombomodulin system and the heparin/anti-thrombin III system are major physiological anticoagulant systems, which may also play a major role in preserving the hepatic microcirculation in xenogeneic liver transplantation. To compensate for the functional incompatibilities of the porcine thrombomodulin (TM)-cofactor activity beyond species for human thrombin, soluble human TM protein was tested in xenogeneic perfusion of the porcine liver. Materials and Methods. The livers were harvested from adult female pigs and perfused through the portal vein (PV) and hepatic artery (HA) for 2 hr, with fresh human blood in group 1 (n=5), fresh porcine blood (10 units/ml) in group 2 (n=5), and fresh human blood with TM (50,000 units/1.5 l) in group 3 (n=5). The tissue PO2 level, tissue blood flow, PV and HA pressures were all continuously monitored. Circulating perfusate and liver tissue samples were periodically obtained for blood chemistry and histologic analyses. Results. The activated protein C (aPC) level was significantly elevated in the TM-treated group 3 (47.5%±3.5% at preperfusion and 51%±2.8% after 120 min of perfusion) in comparison to group 1 (32.3%±7.2% and 35.3±12.0%). The hepatocyte enzyme release of aspartate aminotransferase (AST) was suppressed significantly more in group 3 (238.2±107 IU/l), than in group 1 (672.3±160 IU/l) at 2 hr after reperfusion. In group 3, the tissue PO2 levels and tissue blood flow also remained significantly higher throughout the perfusion. The platelet counts in the perfusate remained significantly higher in group 3 (37.1% to 74.3% of the preperfusion level) than in group 1 (4.4% to 14.7%), after 0 to 80 min of perfusion. According to the histologic findings, the degree of interlobular hemorrhaging and congestion decreased remarkably more in group 3 than in group 1. Conclusion. These findings thus indicated that soluble thrombomodulin protein extracted from human urine remarkably improved hepatic microcirculation in the xenoperfused porcine liver. The thrombomodulin/protein C system might, thus, play an important role in restoring the physiological anticoagulant system in the xenoperfused porcine liver.

Limitations of Exogenous L-Arginine in Exerting a Cytoprotective Effect on Hepatic Ischemia/Reperfusion Injury

Abstract: To test whether or not the L -arginine/nitric oxide (NO) pathway induces a protective effect, we investigated the effect of exogenous L -arginine on hepatic ischemia/reperfusion (I/R) injury, using ex vivo perfusion of the isolated rat liver. The rat liver was removed and preserved in cold saline for 60 min, followed by 120 min of reperfusion with oxygenated perfusate at 37°C. Either 600 mg/kg of L -arginine (groups 1 and 4), D -arginine (group 2), N G -nitro- L -arginine methyl ester ( L -NAME) (group 3), or saline (group 5) were administered through the portal vein starting from 5 min before reperfusion to 5 min after reperfusion. In group 4, 600 mg/kg of L -NAME was preadministered at 10 min prior to the administration of L -arginine. The intrahepatic nitric oxide (NO) levels showed only a temporal elevation (227% ± 70% of the pre-reperfusion levels at 5 min) after reperfusion in group 1. Pretreatment with L -NAME suppressed the elevation of the NO levels immediately after reperfusion in group 4. The lactate dehydrogenase release to the effluent perfusate significantly decreased and the histological findings showed that the sinusoidal damage observed after reperfusion was mitigated in group 1 more than in the other groups. These results thus suggest that exogenous L -arginine produced a relatively small amount of NO and therefore resulted in a slight decrease of hepatic I/R injury.

Adenovirus-mediated gene transfer of triple human complement regulating proteins (DAF, MCP and CD59) in the xenogeneic porcine-to-human transplantation model

In this study, the adenovirus-mediated gene transfer of triple human complement regulating proteins was investigated in xenogeneic pig liver perfusion. The porcine liver was perfused in situ at 4 °C under a pump-driven veno-venous shunt of the portal vein and inferior vena cava, with 5 to 15×1011 plaque-forming units (pfu) of adenovirus vector (group 1: AxCALacZ; 2: AxCACD59; 3: AxCACD59 + AxCADAF; 4: AxCACD59 + AxCADAF + AxCAMCP) for 1 h (for each, n=3). The livers were harvested 24 h after gene transfer and then were reperfused ex-vivo with fresh human blood for 2 h. In immunohistochemical staining, each complement regulating protein (CRP) showed a distribution similar to that of the LacZ expression. The C3 levels in the perfusate were also maintained at higher levels in group 4 from 60 to 120 min after reperfusion (C3: 85% to 95% of the initial level) than in groups 1 to 3 (C3: 80% to 90% of the initial level) from 60 to 120 min after reperfusion. The complement deposition on the porcine liver [C3, membrane attack component (MAC)] decreased significantly more in group 4 than in groups 1 to 3. In conclusion, the adenovirus-mediated multiple gene transfer of human CRPs (hCRPs) was found to effectively suppress the complement activation in xenogeneic pig liver perfusion.

Enteritis Cystica Profunda Presenting as Ileoileal Intussusception in a Child: Report of a Case

We report the case of a 3-month-old male infant with small bowel intussusception caused by enteritis cystica profunda (ECP). The baby was admitted because he was refusing to feed, and was passing “redcurrant jelly” -like stools. A palpable mass was identified, and abdominal ultrasonography showed a mass with a lumen and lumen appearance. We performed laparotomy and resected the segment of bowel containing the mass. The resected segment had enteritis cystica profunda, which was considered to have precipitated the intussusception. A review of the English medical literature revealed only three other cases of children with similar symptoms in the last 30 years.

CT of internal hernia through a defect of the perirectal fossa

We report a case of internal hernia due to a peritoneal defect of the perirectal fossa. This condition is extremely rare and has been reported in the literature only once. This is the first independent case report. CT findings as well as the differential diagnosis of the condition are discussed.

Adenovirus-mediated gene transfer of triple human complement regulating proteins (DAF, MCP and CD59) in the xenogeneic porcine-to-human transplantation model. Part I: in vitro assays using porcine aortic endothelial cells.

We assessed whether the adenovirus-mediated gene transfer of triple human complement regulating proteins (hCRPs) to the porcine aortic endothelium (PAE), could possibly exert a synergistic effect to inhibit human complement activation. Adenovirus vectors, encoding E.Coli β-galactosidase (AxCALacZ), human membrane cofactor protein (MCP) (AxCAMCP), decay-accelerating factor (DAF) (AxCADAF), and CD59 (AxCACD59) were produced by the COS-TPC method. AxCALacZ was transfected to porcine aortic endothelium cells (PAECs) under various multiplicities of infection (MOI) to determine the efficiency of adenovirus-mediated gene transfer by 5-bromo-4-chloro-3-indolyl β-D-galactopyranoside (X-gal) staining. The mRNA expressions of transfected CRPs were examined by reverse transcriptase-polymerase chain reaction (RT-PCR). Cellular damage to the PAEC was assessed by an MTT assay. PAEC was most efficiently transfected with the LacZ gene at 103 MOI/60-min incubation time (89.1%). In all samples transfected with the CRP gene, the corresponding mRNAs were detected in the RT-PCR. In the MTT assay, PAECs co-cultured with 20% human serum, showed the highest cellular viability after gene transfer of triple CRPs (117.7%), when compared with those of marker LacZ, single or double CRPs. The adenovirus-mediated multiple gene transfer of CRPs may thus be an efficient method for suppressing complement activation in the porcine-to-human model of hyperacute rejection.

Colonic stricture with filiform polyposis in Crohn's disease

A 41-year-old man with a 5-year history of Crohns disease presented with abdominal distention, right lower quadrant pain and weight loss for 4 weeks. On physical examination, the abdomen was distended with right lower quadrant tenderness. Plain radiograph of the abdomen disclosed marked dilation of the ascending colon due to a stricture at the hepatic flexure and intraluminal polypoid filling defects that suggested the presence of postinflammatory polyps (figure 1). Colonoscopy failed to disclose the precise cause …

Pneumatosis intestinalis and hepatic portal venous gas in Crohn's disease.

Dear Sir, A 44-year-old man with a 16-year history of ileal-colonic Crohns disease (CD) presented with acute onset severe abdominal pain and vomiting. On examination, he was febrile and a distended and generalized tender abdomen was noted with signs of peritoneal irritation. Laboratory tests revealed increased white blood cell count of 12,500/mm3. The other laboratory values were within normal range. Computed tomography (CT) scan disclosed pneumoperitoneum and dilated loops of the small …

Clinical implications of quantitative pathological and immunohistochemical markers for lymph node metastasis in esophageal cancer patients based on preoperative treatment status

BackgroundWhether the prognostic abilities of markers of lymphatic spread are affected by preoperative chemotherapy or chemoradiotherapy for esophageal cancer has not been clarified. The purpose of this study was to determine significant prognostic predictors related to lymphatic spread in potentially curable esophageal cancer according to preoperative treatment status.MethodsThe prognostic significance of quantitative pathological and immunohistochemical markers of lymphatic spread was determined in 80 esophageal cancer patients undergoing R0 resection with or without preoperative treatment.ResultsUnivariate analysis revealed that the presence or absence of immunohistochemical nodal micrometastasis (iNM), number of pathological nodal metastases (pNM) and iNM, and the ratios of pNM and iNM to removed nodes were significant prognostic predictors in patients undergoing esophagectomy without preoperative treatment. In contrast, only the presence or absence of pNM, number of pNM, and pNM ratio were significant prognostic indicators in patients undergoing esophagectomy after preoperative treatment. Multivariate analysis revealed that the number of iNM, a novel prognostic indicator found in the present study, was the only independent prognostic predictor in the former patients, whereas the number of pNM was the only independent prognostic predictor in the latter patients.ConclusionsIn esophageal cancer, the prognostic values of factors related to lymphatic spread depend on the patient’s preoperative treatment status. Two or more pNM indicated poor prognosis after esophagectomy in patients undergoing preoperative treatment for advanced disease. However, 2 or more iNM indicated poor prognosis after esophagectomy in patients undergoing upfront esophagectomy for less advanced disease.