A case of Wilson’s disease with characteristic laparoscopic findings

A 44-year-old male was pointed out liver function abnormality by medical check-up. Blood examination and computed tomography showed liver cirrhosis. Then, he was referred to our hospital for further examination. After blood test, viral markers revealed previous infection of hepatitis B virus (HBV). We estimated the etiology of his liver disease as previous HBV infection. On laparoscopic examination, his liver surface was nodular with mixed yellowish nodules and ash gray to copper-colored nodules in the diameter of 3–10 mm. There were large regenerative nodules in segments 3 and 4. Large regenerative nodules and irregular steatosis were contradictory to HBV-related liver cirrhosis, so then we supposed Wilson’s disease. The amount of copper excretion in the urine was 326.6 μg (>100 μg/24 h). After D-penicillamine administration, urinary copper excretion increased to 2151.5 μg/24 h. Though hepatic copper concentration was 174.5 μg/g wet tissue (>200 μg/g wet tissue), his laboratory data fulfilled the Leipzig diagnostic criteria proposed by EASL. Laparoscopic examination with liver biopsy has advantages to survey many disease-specific findings on liver surface and to obtain adequate liver sample. Laparoscopic examination is one of the effective procedures for diagnosing relatively rare liver disease like Wilson’s disease.     

Serum levels of soluble adhesion molecules as prognostic factors for acute liver failure

Background/Aims: In patients with septic shock, the degree of liver dysfunction is correlated with serum levels of soluble intercellular adhesion molecule (sICAM)-1. We aimed to assess the usefulness of serum levels of soluble adhesion molecules as prognostic factors for acute liver failure (ALF). Methods: Serum levels of soluble platelet endothelial cell adhesion molecule (sPECAM)-1, sICAM-3, soluble endothelial (sE) selectin, sICAM-1, soluble platelet selectin, and soluble vascular cell adhesion molecule-1 on admission were measured in 37 ALF patients and 34 healthy controls. Results: Twenty-two ALF patients (59%) reached to fatal outcomes. Serum levels of sPECAM-1, sICAM-3, sE-selectin and sICAM-1 were higher in ALF patients than healthy controls. In 37 ALF patients, by the multivariate logistic regression analysis, ratio of direct to total bilirubin (per 0.1 increase; OR 0.11, 95% CI 0.01-0.99), serum sPECAM-1 level (per 100 ng/ml increase; OR 4.37, 95% CI 1.23-15.5) and serum sICAM-1 level (per 100 ng/ml increase; OR 0.49, 95% CI 0.27-0.89) were associated with fatal outcomes. Using receiver operating characteristics curve, each area under the curve of serum sPECAM-1 and sICMA-1 levels as prognostic factors was 0.71 and 0.74, respectively. Conclusion: Serum sPECAM-1 and sICAM-1 levels may be useful for predicting the prognosis of ALF.     

Fulminant hepatitis: Who survives without liver transplantation?

Aim: In order to rescue more patients with fulminant hepatitis (FH) in a setting of the shortage of liver grafts, it is important not only to determine the suitable timing for liver transplantation (LT) but also to reduce avoidable operations for patients surviving without LT. This study aimed to identify prognostic parameters for survival without LT in FH patients. Methods: In 96 FH patients who did not receive LT, we examined prognostic parameters at the time of the diagnosis of FH, which were associated with patient's survival. Results: Fifty‐three patients (55%) were female. The median age was 48 years. At the time of the diagnosis of FH, hepatic coma grade was II in 63 patients (66%), III in 22 (23%) and IV in 11 (11%). Forty‐six patients (48%) were in a state of systemic inflammatory response syndrome (SIRS). Four parameters of age (<45 years), SIRS (no), direct bilirubin/total bilirubin ratio (>0.65), and total bilirubin (<12.0 mg/dL) were associated with patient's survival. Overall survival rate of eight patients ulfilling all four parameters were 88%. In 17 patients fulfilling any three parameters, 2‐week, 4‐week and overall survival rates were 82%, 77% and 71%, respectively. On the other hand, overall survival rate of 38 patients fulfilling any one parameter or none was less than 10%. Conclusions: Patients fulfilling all four parameters will be successfully treated without LT. In patients fulfilling any three parameters, intensive care including artificial liver support in expectation of hepatic regeneration during a few weeks may be possible.     

Discovery of Synthetic Leishmania Inhibitors by Screening of a 2‐Arylbenzothiophene Library

Tamoxifen has been shown to be active in vitro against Leishmania and effective in the treatment for leishmaniasis in murine models. Through the screening of a compound library of estrogen receptor modulator analogs, we identified the major characteristics required for antileishmanial activity. To overcome the difficulties presented by tamoxifen's propensity for E/Z isomerization, we used the 2‐arylbenzothiophene compound BTP as a more stable alternative. Directed screening of a small compound library based on BTP led to active compounds against Leishmania. Subsequent structure–activity data for the synthetic 2‐arylbenzothiophenes evaluated in this study indicate that optimal antileishmanial potency is dependent on the presence of two basic side chains. In addition, the primary structural features required for estrogen receptor binding, the phenols, are not required for inhibiting parasitic growth. Significantly, the most active antileishmanial benzothiophenes lack the pharmacophore for estrogen receptor activity and therefore address potential concerns about the undesirable effects of using selective estrogen receptor modulators in women and children with leishmaniasis. Three compounds selected from the screening have shown consistent activity against all species and stages of Leishmania in vitro although improvements in selectivity are needed. These compounds represent viable starting points for further optimization as antileishmanial agents.     

Prognostic model for hepatocellular carcinoma with time-dependent factors

The purpose of this study was to build a prognostic model of hepatocellular carcinoma (HCC) using time-dependent covariates to re-evaluate the prognosis at any stage of the disease. The subjects were consecutive HCC patients who were treated at our institute between 1995 and 2007. We constructed time-fixed and time-dependent prognostic models with a training group (n=336) and compared the prognostic abilities between conventional Cancer of the Liver Italian Program (CLIP) scores, Japan Integrated Staging (JIS) scores, an Okuda classification, and our prognostic models in the testing group (n=227) with the c-index. The time-dependent prognostic model consisted of main tumor size, tumor number, portal vein invasion, distant metastasis, alpha-fetoprotein, des-gamma-carboxy prothrombin (DCP), bilirubin, and albumin and the weighted scores were set for each factor depending on the hazard ratio for the prognosis. The prognostic index was determined by summing the scores. The c-index values for the CLIP scores, JIS scores, Okuda classification, and our time-dependent model were 0.741, 0.727, 0.609, and 0.870, respectively. These results indicate that our time-dependent model can estimate the prognosis of HCC more precisely than traditional time-fixed models and can be used to re-predict the prognosis of HCC.     

Efficacy of hepatic arterial infusion chemotherapy in combination with irradiation for advanced hepatocellular carcinoma with portal vein invasion

Background

The presence of portal vein tumor thrombosis (PVTT) is a poor prognostic factor for patients with hepatocellular carcinomas (HCC). The purpose of this study was to determine the treatment effect of irradiation in combination with hepatic arterial infusion chemotherapy (HAIC) for these patients.

Methods

We retrospectively examined the outcome of 67 HCC patients with PVTT of the main trunk or first branch who received HAIC alone or with concurrent irradiation for PVTT (CCRT).

Results

Thirty-four patients received HAIC, and 33 patients received CCRT. The time to progression (TTP) of PVTT in the CCRT group was significantly longer than in the HAIC group (p < 0.01), and the TTP of intrahepatic nodules in the CCRT group tended to be longer than in the HAIC group (p = 0.06). The objective response rates of intrahepatic nodules (52 vs. 18 %, p < 0.01) and PVTT (45 vs. 18 %, p = 0.01) were both significantly higher in the CCRT group than in the HAIC group, respectively. No significant difference in overall survival was found between the two groups (p = 0.14); however, the median survival time in the CCRT group was longer than that in the HAIC group (12.4 vs. 5.7 months, respectively).

Conclusions

CCRT might be a promising treatment for advanced-stage HCC with PVTT. CCRT prolonged the TTP of intrahepatic nodules and PVTT, and it improved the objective response rate of intrahepatic nodules and PVTT.

     

近红外荧光分子探针用于CT成像及术中导航

目的 制备近红外荧光分子探针,观察其用于增强CT成像及术中导航效果。方法 采用薄膜水化法制备载IR780和全氟溴辛烷(PFOB)的脂质体(IR780@LIP-PFOB),检测其基本理化性质,观察其用于增强体内、外CT成像的效果。以激光共聚焦显微镜和流式细胞仪观察4T1细胞对IR780@LIP-PFOB的摄取情况,以活体荧光成像检测IR780@LIP-PFOB在荷4T1瘤BALB/c小鼠体内的分布,通过冰冻切片观察IR780@LIP-PFOB在肿瘤区和周围非瘤组织的分布;以实时体视荧光成像系统评估IR780@LIP-PFOB用于术中导航的效能。结果 所获IR780@LIP-PFOB大小均匀,呈球形,平均粒径(262.80±117.60)nm,表面电位(－20.10±6.38)mV,IR780包封率为82.92%;用于小鼠体内、外CT可显著增强成像效果。IR780@LIP-PFOB可选择性聚集于4T1细胞周围并于肿瘤区富集,而非瘤组织中未见其明显聚集;用于术中导航可清晰辨识肿瘤组织及其边界。结论 成功制备的近红外荧光分子探针用于小鼠能增强CT成像效果,并支持术中导航。