Shusuke Morizono

Short-term intensive treatment for donors with hepatic steatosis in living-donor liver transplantation.

Background. The use of steatotic livers is associated with increased primary nonfunction in liver transplantation. To reduce the risk of liver injury, we applied a short-term combination therapy of diet, exercise and drugs for 11 living-donor liver transplantation (LDLT) candidates with steatosis. Methods. Subjects were treated with a protein-rich (1000 kcal/day) diet, exercise (600 kcal/day), and bezafibrate (400 mg/day) for 2–8 weeks. Results. The treatment significantly improved macrovesicular steatosis (30±4% vs. 12±2% [mean±SEM], P= 0.0028). Body weight and BMI were significantly reduced (73.7±3.2 kg vs. 66.9±2.9 kg, P=0.0033, 26.4±0.7 kg/m2 vs. 24.1±0.8 kg/m2, P=0.0033). The treatment completely normalized liver function tests and lipid metabolism. Seven treated liver grafts (left lobe) were transplanted to the recipients. We compared transplanted graft function and resected liver function of donors using parameters such as peak total bilirubin, prothrombin time at postoperative day 3, and peak alanine aminotransferase between treated liver (n=7) and donor liver without hepatic steotosis (n=37). The transplanted grafts showed good liver functions, and there was no difference between them with respect to functional parameters. The treated donors also showed good liver functions, and no significant differences in functional parameters. Conclusions. The results of this study indicate that our short-term treatment effectively reduced steatosis and contributed to safer LDLT. Our findings also suggest that even severely steatotic livers can be used for LDLT grafting subsequent to our short-term treatment regimen.

Effect of IL-4 and IL-13 on collagen production in cultured LI90 human hepatic stellate cells

Background: Recently, it has been reported that interleukin 4 (IL‐4) and 13 (IL‐13) directly activate fibroblasts and promote fibrosis. In the process of hepatic fibrosis, the effects of these cytokines on hepatic stellate cells (HSCs) are not well known.

A multi-step, incremental expansion method for radio frequency ablation: Optimization of the procedure to prevent increases in intra-tumor pressure and to reduce the ablation time

Abstract: Background/Aims: Radio frequency ablation (RFA) has been accepted clinically as a useful local treatment for hepatocellular carcinoma (HCC). However, intra‐hepatic recurrence after RFA has been reported. We initially hypothesized that recurrence was attributable to increases in intra‐tumor pressure during RFA, and we subsequently measured the pressure and optimized the procedure.

Evaluation of liver parenchymal pressure and portal endothelium damage during radio frequency ablation in an in vivo porcine model

Abstract: Background/Aims: We previously developed a multi‐step, incremental expansion method (multi‐step method) for radio frequency ablation (RFA) in vitro, which prevented increases in pressure and reduced the ablation time as compared with other methods. In this study, we evaluated liver parenchymal pressure and portal endothelium damage during RFA with different devices and protocols in an in vivo porcine model.

Comparison of tissue pressure and ablation time between the LeVeen and cool-tip needle methods

BackgroundRadio frequency ablation (RFA) has been accepted clinically as a useful local treatment for hepatocellular carcinoma (HCC). However, intrahepatic recurrence after RFA has been reported which might be attributable to increase in intra-tumor pressure during RFA. To reduce the pressure and ablation time, we developed a novel method of RFA, a multi-step method in which a LeVeen needle, an expansion-type electrode, is incrementally and stepwise expanded. We compared the maximal pressure during ablation and the total ablation time among the multi-step method, single-step method (a standard single-step full expansion with a LeVeen needle), and the method with a cool-tip electrode. Finally, we performed a preliminary comparison of the ablation times for these methods in HCC cases.ResultsA block of pig liver sealed in a rigid plastic case was used as a model of an HCC tumor with a capsule. The multi-step method with the LeVeen electrode resulted in the lowest pressure as compared with the single-step or cool-tip methods. There was no significant difference in the ablation time between the multi-step and cool-tip ablation methods, although the single-step methods had longer ablation times than the other ablation procedures. In HCC cases, the multi-step method had a significantly shorter ablation time than the single-step or cool-tip methods.ConclusionWe demonstrated that the multi-step method was useful to reduce the ablation time and to suppress the increase in pressure. The multi-step method using a LeVeen needle may be a clinically applicable procedure for RFA.

Decreased portal flow volume increases the area of necrosis caused by radio frequency ablation in pigs.

Background/aims: Although radio frequency ablation (RFA) has been widely accepted as an effective treatment for hepatocellular carcinoma (HCC), severe complications are not uncommon. Major complications seem to occur as a result of over‐ablation beyond the intended area. As most patients with HCC have underlying cirrhosis, we speculated that decreased portal flow might cause the necrosis associated with RFA. To confirm this hypothesis, we examined the area of necrosis resulting from RFA under varying conditions of portal flow in a porcine model.

Case report: RCAS1, a useful serum marker to predict the recurrence of cancer: Two cases of cholangiocarcinoma and pancreatic cancer

A tumor-associated antigen recognized by 22-1-1 antibody, which was established against the human uterine carcinoma cell line SiSo, was cloned as type II transmembrane protein and designated RCAS1 (1–3). As a result of functional in vitro assays, it has been suggested that the antigen can induce apoptosis on activated immune cells (1). RCAS1 expression has been immunohistochemically demonstrated in various kinds of cancer, and we also reported that the antigen was present in cancer cells of cholangiocarcinoma and pancreatic carcinoma (4, 5). Because RCAS1 also exists in soluble form, we developed an ELISA system to measure serum values of RCAS1 and reported that serum RCAS1 levels were elevated in patients with pancreaticobiliary cancers (5, 6). Therefore, we have suggested that serum RCAS1 is useful as a tumor marker for cancers of bile duct and pancreas and is able to predict relapse. We report here on two patients who had undergone curative operations for primary cancers, cholangiocarcinoma and pancreatic carcinoma, in whom RCAS1 was able to predict relapse several months before its actual detection.

Clinical significance of urinary N1,N12-diacetylspermine levels in patients with hepatocellular carcinoma.

BACKGROUND/AIM N1,N12-diacetylspermine (DiAcSpm), a diacetylpolyamine which was recently identified in urine, appeared to be a useful tumor marker for urogenital cancers. Here we examined the clinical significance of urinary DiAcSpm as a tumor marker for hepatocellular carcinoma (HCC). METHODS Urine samples were collected from patients with HCC and benign liver diseases. Urinary levels of DiAcSpm were measured by ELISA, which was newly developed in order to analyze large numbers of samples. RESULTS The appropriate threshold value was set at 325 nM/g x creatinine. The sensitivity of the DiAcSpm assay for HCC was 65.5% and the specificity calculated between HCC and liver cirrhosis was 76.0%. The percentage of DiAcSpm-positive HCC patients was similar to that for AFP or PIVKA-II. At more advanced clinical stages, the positive percentage of these three markers increased but the DiAcSpm levels appeared to move independently of AFP and PIVKA-II. In HCC patients, the DiAcSpm levels reflected the progression of disease or the effect of treatment. CONCLUSIONS DiAcSpm levels were found to reflect the severity, activity or viability of HCC. Urinary DiAcSpm can therefore be considered one of the useful indexes for patients with HCC.

Composite small cell and mucinous carcinoma originating from the intrahepatic bile duct: report of a case

The biliary tract is a very rare site for the occurrence of extrapulmonary small cell carcinoma. A 68-year-old Japanese female was being followed up for autoimmune hepatitis, and was referred to our hospital because segmental intrahepatic bile duct dilation was found on routine imaging studies, suggesting intrahepatic cholangiocarcinoma. She underwent left lobectomy of the liver and concomitant resection of the caudate lobe. Microscopic examination of the explanted liver showed a primary composite tumor comprising small cell and mucinous carcinomas that originated in the intrahepatic bile duct. Further immunohistochemical studies, including cytokeratin-19 and chromogranin-A staining, showed the two cellular components of the tumor to have similar characteristics. The amphicrine properties indicated that the tumor had a monoclonal origin but with biphenotypic differentiation, which was responsible for the histogenesis of this tumor.

The prognostic role of lactate dehydrogenase serum levels in patients with hepatocellular carcinoma who are treated with sorafenib: the influence of liver fibrosis

BACKGROUND Serum lactate dehydrogenase (LDH) levels could be a prognostic factor for sorafenib-treated patients with several types of solid tumor because it reflects hypoxic circumstances in aggressive tumors. For hepatocellular carcinoma (HCC), however, the prognostic role of LDH has been controversial. Liver fibrosis can potentially cause hypoxia in the liver, which has not been previously studied in the patients with advanced HCC. Thus, we aimed to analyze the prognostic role of LDH based on the degree of fibrosis. METHODS Eighty-nine consecutive patients with HCC (Child-Pugh class A) who were treated using sorafenib were enrolled into this study. Pretreatment characteristics and changes in hepatic functional tests based on early response to sorafenib and serum LDH levels were analyzed. The degree of fibrosis was estimated using the aspartate aminotransferase (AST) to platelet ratio index (APRI), and the tumor response was evaluated after 3 months of sorafenib treatment. RESULTS Overall, five patients discontinued sorafenib within 4 weeks. For the other 84 patients, those with progressive disease (PD) had significantly high pretreatment LDH levels, which correlated with the APRI score but not with the tumor stage. Multivariate logistic analysis revealed that older age and lower pretreatment LDH levels were independent prognostic factors for a better response to sorafenib. In patients who discontinued sorafenib early, three experienced acute liver failure accompanied with an increase in serum LDH. CONCLUSIONS We demonstrated that baseline serum LDH levels in HCC patients were affected by liver fibrosis but not by the tumor stage, and these LDH levels could be a marker for early response to sorafenib. A marked increase in serum LDH levels during sorafenib administration might also indicate subsequent acute liver failure. Close observation of serum LDH levels before and during sorafenib treatment could be useful in managing treatment of patients receiving this therapy.