Koji Hashimoto

The impact of preoperative serum C‐reactive protein on the prognosis of patients with hepatocellular carcinoma

The authors evaluated the significance of the preoperative serum C‐reactive protein (CRP) level as a prognostic indicator in patients with hepatocellular carcinoma (HCC).

Small Graft for Living Donor Liver Transplantation

ObjectiveTo evaluate the impact of graft size on recipients in living donor liver transplantation (LDLT) to establish a clinical guideline for the minimum requirement. Summary Background DataAlthough the minimum graft size required for LDLT has been reported to be 30% to 40% of graft volume (GV)/standard liver volume (SLV), the safety limit of the graft size was unknown. MethodsA total of 33 cases of LDLT, excluding auxiliary transplantation, were reviewed with a minimum observation period of 4 months. The 33 patients were divided into three groups according to GV/SLV: medium-size graft group, small-size graft group, and extra-small graft group. The effect of GV/SLV on graft function, graft regeneration, and survival was evaluated. ResultsThe overall patient survival rate was 94% at a mean follow-up of 15 months with a minimum observation period of 4 months. There were no statistically significant differences in postoperative bilirubin clearance, alanine aminotransferase, prothrombin time, and frequency of postoperative complications among the three groups. One week after transplantation, the regeneration rate (GV at 1 week/harvested GV) in the extra-small and small groups was significantly higher than that of the medium group. The graft and patient survival rates were both 100% in the extra-small group, 75% and 88% in the small group, and 90% and 95% in the medium group. ConclusionsSmall-for-size grafts less than 30% of SLV can be used with careful intraoperative and postoperative management until the grafts regenerate.

SLAM (CD150)-Independent Measles Virus Entry as Revealed by Recombinant Virus Expressing Green Fluorescent Protein

ABSTRACT Wild-type measles virus (MV) strains use human signaling lymphocyte activation molecule (SLAM) as a cellular receptor, while vaccine strains such as the Edmonston strain can use both SLAM and CD46 as receptors. Although the expression of SLAM is restricted to cells of the immune system (lymphocytes, dendritic cells, and monocytes), histopathological studies with humans and experimentally infected monkeys have shown that MV also infects SLAM-negative cells, including epithelial, endothelial, and neuronal cells. In an attempt to explain these findings, we produced the enhanced green fluorescent protein (EGFP)-expressing recombinant MV (IC323-EGFP) based on the wild-type IC-B strain. IC323-EGFP showed almost the same growth kinetics as the parental recombinant MV and produced large syncytia exhibiting green autofluorescence in SLAM-positive cells. Interestingly, all SLAM-negative cell lines examined also showed green autofluorescence after infection with IC323-EGFP, although the virus hardly spread from the originally infected individual cells and thus did not induce syncytia. When the number of EGFP-expressing cells after infection was taken as an indicator, the infectivities of IC323-EGFP for SLAM-negative cells were 2 to 3 logs lower than those for SLAM-positive cells. Anti-MV hemagglutinin antibody or fusion block peptide, but not anti-CD46 antibody, blocked IC323-EGFP infection of SLAM-negative cells. This infection occurred under conditions in which entry via endocytosis was inhibited. These results indicate that MV can infect a variety of cells, albeit with a low efficiency, by using an as yet unidentified receptor(s) other than SLAM or CD46, in part explaining the observed MV infection of SLAM-negative cells in vivo.

Use of steatotic graft in living-donor liver transplantation.

Background. The degree of fatty infiltration in hepatic grafts is known to be an important risk factor for primary graft nonfunction in cadaveric liver transplantation. However, the effect of hepatic steatosis in living-donor liver transplantation (LDLT) has not yet been well defined. In this study, we evaluated the impact that the degree of hepatic graft steatosis has on the outcome of LDLT. Methods. Sixty consecutive donors and recipients who underwent LDLT between October 1996 and August 2001 at Kyushu University Hospital were the subjects of this study. The pathologic findings of the prereperfusion biopsy of the graft were classified into the following three groups according to the degree of macrovesicular steatosis: None (n=23), 0% steatosis; Mild (n=23), 0% to 20% steatosis; and Moderate (n=6), 20% to 50% steatosis. Liver function tests including total bilirubin (at postoperative day [POD] 7), the peak alanine aminotransferase (ALT) and prothrombin time (at POD 3), and both patient and graft survival were compared among the groups. Furthermore, we also compared the donor parameters including the peak ALT and total bilirubin (at POD 3) and the operative time, blood loss, and length of hospital stay after surgery. Results. The 1-year patient and graft survival were comparable among the groups. The peak ALT was significantly higher in the Moderate group (606±641 IU/L) than in the None (290±190 IU/L) and Mild (376±296 IU/L) groups. Total bilirubin (POD 7) and prothrombin time (POD 3) were comparable among the groups. The donor parameters were comparable among the groups except for the fact that the donor body weight of the Mild and Moderate groups were significantly heavier (P <0.0001) than that of the None group. Conclusions. In conclusion, the use of a fatty liver graft up to the moderate level can be justified in LDLT, even though ischemia-reperfusion injury tends to be severe in such grafts.

Mortality of Intra-Abdominal Desmoid Tumors in Patients With Familial Adenomatous Polyposis A Single Center Review of 154 Patients

Introduction:Intra-abdominal desmoid tumors are one of the leading causes of death in patients with familial adenomatous polyposis. Their behavior is unpredictable and their biology is poorly understood, accounting for the lack of a standardized medical and surgical approach. The aim of this study was to evaluate the mortality rate of patients with intra-abdominal desmoid tumors and to identify prognostic factors for the evolution of the disease. Materials and Methods:A total of 154 patients with intra-abdominal desmoid tumors were included in the study. Each tumor was staged and each patient was categorized according to the stage of their most advanced tumor. Mortality was analyzed and the univariate risk factors associated with survival were included in a multivariable Cox regression model. A scoring system was derived from the multivariate analysis to refine outcomes within stages. Results:Five-year survival of patients with stage I, II, III, and IV intra-abdominal desmoid tumor were 95%, 100%, 89%, and 76% respectively (P < 0.001). Severe pain/narcotic dependency, tumor size larger than 10 cm, and need for total parenteral nutrition were shown to further define survival within stages. Five-year survival rate of stage IV patient with all of the above-mentioned risk factors was only 53%. Conclusions:Our study confirmed the validity of the staging system to predict mortality in patients with intra-abdominal desmoid tumors and identified additional risk factors able to better define the risk of death within each stage. Risk stratification is crucial in directing patients with advanced disease and poor prognosis to the most appropriate medical and surgical options.

The PPARγ Ligand, 15d-PGJ2, Attenuates the Severity of Cerulein-Induced Acute Pancreatitis

Introduction The prostaglandin D2 metabolite, 15d-PGJ2, a potent natural ligand for peroxisome proliferator–activated receptor &ggr; (PPAR&ggr;), exerts antiinflammatory effects by inhibiting the induction of inflammatory response genes and NF-&kgr;B-dependent transcription. Aim To determine whether 15d-PGJ2 decreases the severity of secretagogue-induced acute pancreatitis (AP) and to assess cellular mechanisms contributing to these effects. Methodology Swiss Webster mice were injected with either saline or cerulein (50 &mgr;g/kg) hourly for 8 hours and received either 15d-PGJ2 (2 mg/kg) or vehicle 1 hour before and 4 hours after induction of AP. Results Treatment with 15d-PGJ2 significantly attenuated AP, as determined by histologic assessment of edema, vacuolization, inflammation, and necrosis. This attenuation was associated with decreased cyclooxygenase-2 (COX-2) and intercellular adhesion molecule-1 (ICAM-1) expression and decreased serum and pancreatic IL-6 levels. Treatment with 15d-PGJ2 markedly inhibited NF-&kgr;B DNA-binding activity, and, moreover, this decreased activity was associated with a concomitant inhibition of I&kgr;B protein degradation. Conclusion Our findings demonstrate that 15d-PGJ2 attenuates the severity of AP most likely through the inhibition of COX-2 expression, IL-6 production, and NF-&kgr;B activation. Ligands specific for PPAR&ggr; may represent novel and effective means of clinical therapy for AP.

Occlusion and subsequent re-canalization in early duodenal development of human embryos: integrated organogenesis and histogenesis through a possible epithelial-mesenchymal interaction.

Histogenesis of the duodenum, especially changes in the epithelium in relation to temporal occlusion and re-canalization of the lumen, was investigated by light microscopy together with morphometric analysis, as well as by scanning and transmission electron microscopy of 133 externally normal human embryos ranging from Carnegie stage 12 to 23. A series of morphogenetic events passed the duodenum in a cranio-caudal (proximo-distal) wave like fashion during the period examined. They included: (1) a decrease in the caliber and area of the lumen, (2) ’occlusion’ of the lumen, (3) vacuole formation, (4) ’re-canalization’ and villi formation. The only exemption to this rule was that, in the upper part of the duodenum, the lumen was not obliterated in the embryos examined. Morphometric analyses revealed that both the area of the epithelium and the number of epithelial cells decreased during the ’occlusion’ phase. This result suggests that, unlike the classical view, epithelial cell proliferation does not play an important role in occluding the lumen, but the predominant morphogenetic event during this phase is convergence of the epithelial cells to elongate the duodenum. Apoptosis, contrary to some classical views, decreased during the ’re-canalization’ phase, and it appeared to be involved in the formation of the small lumens in the epithelial ’plug’ and in villi formation, but not in enlarging the secondary lumens. The secondary small lumens in the occluded lumen were frequently formed near the border between the central ’plug’ and peripheral basal cells on the basement membrane. This and other findings of concentric differentiation in both the epithelial and mesenchymal layers suggested a possible control mechanism by the epithelium-mesenchymal interaction on human duodenal morphogenesis and histogenesis. The present electron microscopic observations also provided details on the mechanisms involved in the enlargement of the secondary lumen and differentiation of villi. The implications of these findings to duodenal anomalies are also discussed.

Beneficial effects of 3-dimensional visualization on hepatic vein reconstruction in living donor liver transplantation using right lobe graft.

BACKGROUNDnRecently, virtual operation planning and navigation systems have been introduced in the field of neurosurgery and orthopedic surgery. We report here the beneficial effects of 3-dimensional (3D) visualization on hepatic venous reconstruction in living donor liver transplantation (LDLT) using right lobe graft.nnnMETHODSn3D-image reconstruction of the liver was rendered with 3-mm slices of helical computed tomography (CT) data using zioM900 (Zio Software Inc., Tokyo, Japan). To understand the anatomy of the donors vessels and design an operation plan, a picture of the vessels in and around the liver was reconstructed.nnnRESULTSnThe 3D image demonstrated two short hepatic veins next to the inferior right hepatic vein (IRHV) as well as a large IRHV. The 3D image showed a more precise diameter of the right hepatic vein (RHV) and the IRHV and a more accurate distance between the two hepatic veins than did images measured by 2-dimensional CT. This preoperative information allowed the donor surgeon to dissect the inferior vena cava (IVC) and hepatic veins with reduced blood loss because of reduced risk of injury to the blood vessels. The 3D image revealed that both the RHV and the IRHV branched off at the same angle from the cylindrical IVC. Preoperative planning based on this information secured smooth anastomosis.nnnCONCLUSIONSn3D visualization is useful for hepatic venous reconstruction of the recipient as well as for donor surgery in LDLT using right lobe graft.

Correlation between TGF-β1 and p21 (WAF1/CIP1) expression and prognosis in resectable invasive ductal carcinoma of the pancreas

Transforming growth factor-β1 (TGF-β1) inhibits the growth of a variety of epithelial cells; however, in many types of tumors it loses its inhibitory effect. p21(WAF1/CIP1), one of the cyclin-dependent kinase (Cdk) inhibitors induced by TGF-β1, is considered a downstream effector of the growth-inhibitory function of TGF-β1. We assessed the clinicopathologic significance of TGF-β1 and p21 expression in resectable invasive ductal carcinoma (IDC) of the pancreas. Immunohistochemical examination of the expression of TGF-β1 and p21 in 62 patients revealed positive expression of TGF-β1 in 28 (45%) and of p21 in 25 (40%) of the 62 patients, and a significant correlation between the two expressions. The survival curve of patients with TGF-β1(+) tumors was significantly higher than that of patients with TGF-β1(−) tumors; p21(+) patients showed a higher survival curve than did p21(−) patients, but the difference was not statistically significant. Simultaneous analysis of TGF-β1 and p21 expression showed that the patients with TGF-β1(+)/p21(+) tumors had a significantly better prognosis than the others. Multivariate analysis showed that TGF-β1 was a significantly low risk factor for death due to IDC. The concurrent evaluation of TGF-β1 and p21 expression would be an effective tool in the prediction of the prognosis of patients with pancreatic cancer.

A Simulation-Based Soft Error Estimation Methodology for Computer Systems

This paper proposes a simulation-based soft error estimation methodology for computer systems. Accumulating soft error rates (SERs) of all memories in a computer system results in pessimistic soft error estimation. This is because memory cells are used spatially and temporally and not all soft errors in them make the computer system faulty. Our soft-error estimation methodology considers the locations and the timings of soft errors occurring at every level of memory hierarchy and estimates the soft errors of the whole system using instruction-set simulation. Our experiment demonstrates that the reliability of computer systems depends on not only SERs of memories but also the behavior of software running on the systems