A case of acute autoimmune hepatitis presenting after incomplete-type CREST syndrome and chronic thyroiditis.

A 55-year-old woman was admitted to our hospital with acute hepatitis of unknown origin. She had a history of incomplete-type CREST (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) syndrome and chronic thyroiditis approximately 10 years earlier. Although she achieved spontaneous remission without treatment, she was re-admitted 18 months later due to recurrent liver dysfunction. Liver biopsy was performed as we strongly suspected autoimmune hepatitis despite her normal serum immunoglobulin G level. Liver biopsy findings were histologically compatible with autoimmune hepatitis, and administering prednisolone (30 mg/day) led to a prompt recovery of her liver dysfunction. No relapse occurred during the tapering of prednisolone to a maintenance dose of 5 mg/day. Here we report a rare case of autoimmune hepatitis in a patient with a history of incomplete-type CREST syndrome and chronic thyroiditis.

Clinical significance of autoantibodies to p53 protein in patients with autoimmune liver diseases.

BACKGROUND: Autoantibodies to p53 (anti-p53) are rarely present in the sera of patients with autoimmune diseases or the sera of patients with malignancies. OBJECTIVE: To examine the prevalence of anti-p53 in patients with autoimmune liver disease including autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), AIH/PBC overlap syndrome (AIH/PBC OS) and primary sclerosing cholangitis (PSC), and to determine the clinical significance of anti-p53 in autoimmune liver diseases. METHODS: Forty patients with AIH, 41 patients with PBC, eight patients with AIH/PBC OS and five patients with PSC were enrolled. Anti-p53 and antibodies to double-stranded DNA (anti-ds-DNA) were analyzed using commercially available ELISA kits. Demographic, laboratory and histological data were compared between the AIH groups seropositive and seronegative for anti-p53. RESULTS: Six of 40 (15.0%) patients with AIH and four of eight (50.0%) patients with AIH/PBC OS were positive for anti-p53. One of 41 (2.4%) patients with PBC was also positive for anti-p53, but all five patients with PSC were negative, indicating a significantly higher prevalence of anti-p53 in patients with AIH or AIH/PBC OS compared with patients with PBC. None of the AIH patients positive for anti-p53 progressed to hepatic failure or relapsed after immunosuppressive treatment. Titres of anti-ds-DNA in patients with AIH and AIH/PBC OS significantly correlated with titres of anti-p53 (r=0.511; P=0.0213). CONCLUSION: The emergence of anti-p53 is likely to be useful for discriminating AIH or AIH/PBC OS from PBC and helpful for predicting favourable prognoses in patients with AIH. DNA damage may trigger the production of anti-p53 in patients with AIH or AIH/PBC OS.

Clinical relevance of antibodies to cardiolipin in patients with chronic hepatitis C.

The significance of antibodies to cardiolipin (anti-CL) remains uncertain in patients with chronic hepatitis C (CH-C). The main purpose of this study was to elucidate the clinical characteristics of patients with CH-C seropositive for anti-CL. The prevalence of anti-CL and clinical parameters associated with anti-CL in those patients were examined. Six of the 45 (13%) patients with CH-C had anti-CL. However, none of these six CH-C patients fulfilled the criteria for antiphospholipid syndrome. Serum triglyceride and apolipoprotein B (ApoB) levels in CH-C patients with anti-CL were significantly higher than those in CH-C patients without anti-CL. Serum triglyceride levels positively correlated with serum ApoB levels. CH-C patients with anti-CL had significantly more progressive hepatic fibrosis than those without anti-CL. The degree of 8-hydroxy 2'-deoxyguanosine (8-OHdG) expression in the liver tissue was more severe in CH-C patients with anti-CL than in those without it. However, the emergence of anti-CL in CH-C patients was independent of insulin resistance, hepatic steatosis, and iron overload. These findings suggest that the emergence of anti-CL is associated with oxidative stress and that CH-C patients seropositive for anti-CL have clinical characteristics of hypertriglyceridemia, which derives from the facilitation of ApoB synthesis, and progressive hepatic fibrosis.

[A case of hemolytic uremic syndrome after adjuvant chemotherapy with gemcitabine in a patient with pancreatic cancer].

A 63-year-old man with Stage IVa pancreas tail cancer was admitted for a distal pancreatectomy and splenectomy; adjuvant chemotherapy with gemcitabine was also administered. The chemotherapy was terminated after 16 courses due to hemolytic anemia, thrombocytopenia and renal dysfunction. Plasma exchange was performed; however the patient's renal function was diminished, requiring chronic hemodialysis. Physicians should be cautious of hemolytic uremic syndrome as a possible adverse reaction to gemcitabine and be aware that tests are needed for its early detection.

Virulent strain of hepatitis E virus genotype 3, Japan.

Hepatitis E virus (HEV) genotype 3, which usually causes asymptomatic infection in Japan, induced severe hepatitis in 8 patients. To better understand genetic features of HEV associated with increased virulence, we determined the complete or near-complete nucleotide sequences of HEV from these 8 patients and from 5 swine infected with genotype 3 strain swJ19. Phylogenetic analysis showed that the isolates from the 8 patients and the 5 swine grouped separately from the other genotype 3 isolates to create a unique cluster, designated JIO. The human JIO-related viruses encoded 18 amino acids different from those of the other HEV genotype 3 strains. One substitution common to almost all human HEV strains in the JIO cluster was located in the helicase domain (V239A) and may be associated with increased virulence. A zoonotic origin of JIO-related viruses is suspected because the isolates from the 5 swine also possessed the signature V239A substitution in helicase.

Clinical characteristics of patients with hepatitis C virus-related chronic liver disease seropositive for anticentromere antibody.

The association between anticentromere antibody (ACA) and hepatitis C virus (HCV) infection remains unclear. We subjected eight patients with HCV-related chronic liver disease (CLD) seropositive for ACA to a battery of clinical and laboratory tests. The patient cohort was dominated by females, and four of the eight (50%) patients had a concomitant autoimmune disease. All of the patients had high titers of ACA (>or=1:320). The histological activity index scores in chronic hepatitis C (CH-C) patients with ACA were significantly higher than those in CH-C patients without antinuclear antibody (ANA) (12.8 +/- 1.8 vs. 8.3 +/- 4.5, P = 0.0372). The frequency of human leukocyte antigen (HLA) DR-8 in patients with HCV-related CLD seropositive for ACA was significantly higher than that in patients with CH-C seronegative for ANA (71 vs. 18%, P = 0.0108). These findings suggest that ACA is induced by chronic HCV infection in association with HLA DR-8, and that CH-C patients with ACA exhibit more severe hepatic fibrosis and inflammation than CH-C patients without ANA.

A combination therapy of ethanol injection and radiofrequency ablation under general anesthesia for the treatment of hepatocellular carcinoma.

AIM: To summarize the effects of laparoscopic ethanol injection and radiofrequency ablation (L-EI-RFA), thoracoscopic (T-EI-RFA) and open-surgery assisted EI-RFA (O-EI-RFA) under general anesthesia for the treatment of hepatocellular carcinoma (HCC). METHODS: Time-lag performance of RFA after ethanol injection (Time-lag PEI-RFA) was performed in all cases. The volume of coagulated necrosis and the applied energy for total and per unit volume coagulated necrosis were examined in the groups treated under general (group G) or local anesthesia (group L). RESULTS: The results showed that the total applied energy and the applied energy per unit volume of whole and marginal, coagulated necrosis were significantly larger in group G than those in the group L, resulting in a larger volume of coagulated necrosis in the group G. The rate of local tumor recurrence within one year was extremely low in group G. CONCLUSION: These results suggest that EI-RFA, under general anesthesia, may be effective for the treatment of HCC because a larger quantity of ethanol and energy could be applied during treatment under painfree condition for the patients.

Fibrosis Staging Using Direct Serum Biomarkers is Influenced by Hepatitis Activity Grading in Hepatitis C Virus Infection.

BACKGROUND: Chronic liver diseases (CLDs) generally progress from inflammation to fibrosis and finally to carcinogenesis. Staging of liver fibrosis progression is inevitable for the management of CLD patients. The purpose of this study was to compare the diagnostic abilities of Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA-M2BP), Enhanced liver fibrosis (ELF) score, Fibrosis-4 index, and AST to platelet ratio index (APRI) based on histopathological analysis of liver biopsy samples, from patients with positive Hepatitis C Virus (HCV) infection. METHODS: Japanese patients with HCV infection who underwent liver biopsy examinations were enrolled in this study. WFA-M2BP levels and ELF scores were calculated using preserved serum samples. The fibrosis staging and activity grading were assessed using a modified METAVIR score. RESULTS: A total of 122 patients were enrolled; the cohort included 27 patients with stage 1, 66 with stage 2, 20 with stage 3, and nine with stage 4 fibrosis. All four biomarkers distinguished stage 3 and stage 2 fibrosis. ROC curves revealed that all four fibrosis biomarkers presented AUC values greater than 0.8. Each of the four biomarkers in stage 2 was significantly different between the activity grade 1 and 2 groups. CONCLUSION: Fib-4 index and APRI were comparable with WFA-M2BP and ELF score in the diagnosis of advanced liver fibrosis in Japanese patients with HCV infection. All four biomarkers of liver fibrosis were influenced by histopathological activity grading, which implies that liver biopsy should be the gold standard to evaluate liver fibrosis staging even though several noninvasive biomarkers have been investigated well.

Identification of c-Yes expression in the nuclei of hepatocellular carcinoma cells: involvement in the early stages of hepatocarcinogenesis.

It is thought that the subcellular distribution of Src-family tyrosine kinases, including c-Yes binding to the cellular membrane, is membranous and/or cytoplasmic. c-Yes protein tyrosine kinase is known to be related to malignant transformation. However, the expression patterns of c-Yes in hepatocellular carcinoma (HCC) remains unknown. In the present study, we report that c-Yes is expressed not only in the membrane and cytoplasm, but also in the nuclei of cancer cells in some human HCC tissues and in a human HCC cell line. We examined the expression and localization of c-Yes in human HCC cell lines (HLE, HLF, PLC/PRF/5 and Hep 3B) by Western blotting and immunohistochemical analyses; we also examined the expression of c-Yes by immunohistochemistry and Western blotting in the tissues of various liver diseases, including 39 samples from HCC patients. We used an antibody array to detect proteins that bind to nuclear c-Yes in PLC/PRF/5 cell line. c-Yes was found to be expressed in the membranes and cytoplasm of HLE, HLF and Hep 3B HCC cells; it was also detected in the nuclei in addition to the membranes and cytoplasm of PLC/PRF/5 HCC cells. HCC with nuclear c-Yes was detected in 5 of 39 cases (13.0%), and nuclear c-Yes expression was not detected in normal, chronic hepatitis or cirrhotic livers. All HCCs with nuclear c-Yes expression were well-differentiated, small tumors at the early stages. In the PLC/PRF/5 cell line, the nuclear localization of c-Yes with cyclin-dependent kinase 1 was confirmed by a protein antibody array. In conclusion, nuclear c-Yes expression was found in cancer cells at the early stages of hepatocarcinogenesis, suggesting that nucleus-located c-Yes may be a useful marker to detect early-stage HCC.

Sequential assessment of the intrahepatic expression of epidermal growth factor and transforming growth factor-beta1 in hepatofibrogenesis of a rat cirrhosis model.

Responses of the liver to chronic injury include inflammation, regeneration and fibrosis, which finally lead to cirrhosis. The cause of liver cirrhosis appears to be impaired proliferative capability of hepatocytes caused by continuous hepatic damage, and subsequent accumulation of extracellular matrix produced by hepatic stellate cells (HSCs). Epidermal growth factor (EGF) and transforming growth factor-beta1 (TGF-beta1) play a crucial role in hepatocyte proliferation and hepatofibrogenesis, respectively. However, sequential analyses of the intrahepatic expression of EGF and TGF-beta1 in the course of cirrhosis development have not been examined fully. In the present study, liver cirrhosis was produced in rats by intraperitoneal administration of dimethylnitrosamine (DMN), and intrahepatic mRNA expression levels of proliferating cell nuclear antigen (PCNA), EGF and TGF-beta1 were quantitatively estimated by a real-time reverse transcription-polymerase chain reaction method. Histological and semiquantitative densitometric examination of liver sections revealed that the accumulation of extracellular matrix components was increased according to the period of DMN treatment. Histological examination of liver sections of rats treated with DMN for 4 and 6 weeks revealed pre-cirrhosis and cirrhosis, respectively. Intrahepatic mRNA expression levels of PCNA and EGF correlated well. Expression levels of both molecules were increased significantly during the course of cirrhosis development, but decreased significantly at the time of complete cirrhosis manifestation. In contrast, intrahepatic TGF-beta1 expression was increased significantly according to the period of DMN treatment, and reached a peak at the time of cirrhosis manifestation. These results suggest that proliferative capability of hepatocytes was impaired by continuous liver damage due, in part, to the decrease of a hepatocyte mitogen EGF, and that increased intrahepatic TGF-beta1 activated HSCs to retrieve space lost by hepatocyte destruction, resulting in complete cirrhosis manifestation.

Time-lag performance of radiofrequency ablation after percutaneous ethanol injection for the treatment of hepatocellular carcinoma.

We have previously reported that the combination therapy of percutaneous ethanol injection and radiofrequency ablation (PEI-RFA) was more effective than RFA alone to induce wider coagulated necrosis for the treatment of hepatocellular carcinoma (HCC). In the present study, the effect of time-lag performance of RFA after PEI was evaluated under the same ablation condition as PEI-RFA by analyzing the volume of coagulated necrosis, the energy requirement for ablation and the amount of ethanol injected into HCC. The comparative study between time-lag PEI-RFA and no time-lag PEI-RFA showed that the total energy requirement and the energy requirement per unit volume for whole and marginal coagulated necrosis were significantly smaller in the time-lag group than in the no time-lag PEI-RFA group. In time-lag PEI-RFA, the volume of coagulated necrosis induced positively correlated with the amount of ethanol injected into HCC as previously observed in PEI-RFA treatment. These results suggest that time-lag PEI-RFA can induce comparable coagulated necrosis with a smaller energy requirement than no time-lag PEI-RFA, and that time-lag PEI-RFA is likely to be less invasive than no time-lag PEI-RFA for inducing comparable coagulated necrosis. Thus, time-lag performance of RFA after PEI may make RFA treatment more effective and less invasive for the treatment of patients with HCC.

Relationship between the proliferative capability of hepatocytes and the intrahepatic expression of hepatocyte growth factor and c-Met in the course of cirrhosis development in rats.

Liver cirrhosis is the fatal end stage of various chronic liver diseases. One of the most important causes of liver cirrhosis appears to be an impaired proliferative capability of hepatocytes caused by continuous hepatic damage. Hepatocyte growth factor (HGF) and its specific receptor, c-Met, play a pivotal role in hepatocyte proliferation. However, the relationship between the proliferative capability of hepatocytes and the intrahepatic expression of HGF and c-Met during the course of cirrhosis development has not been studied fully. In the present study, liver cirrhosis was produced in rats by intraperitoneally administering dimethylnitrosamine (DMN) and intrahepatic expression levels of HGF and c-Met were quantitatively estimated using a real-time reverse transcription-polymerase chain reaction (RT-PCR) method. Histological examination of liver sections and biochemical estimation of serum levels of transaminase revealed that the degree of hepatocyte destruction was elevated gradually during cirrhosis development in the DMN-induced rat cirrhosis model. The proliferative capability of hepatocytes estimated immunohistochemically by proliferating cell nuclear antigen staining was markedly increased at an early stage of cirrhosis development. However, it was gradually decreased thereafter and suppressed substantially at the time of cirrhosis manifestation. Intrahepatic HGF expression was also increased significantly during the course of cirrhosis development but decreased significantly at the time of cirrhosis manifestation. Conversely, there was a tendency for the intrahepatic expression of c-Met to decrease from an early stage of cirrhosis development and intrahepatic c-Met expression was decreased significantly at the time of cirrhosis manifestation. These results suggest that the highly proliferative capability of hepatocytes at an early stage of cirrhosis development is induced by increased intrahepatic HGF expression. However, both HGF and c-Met expression levels in the liver are decreased significantly there-after. Accordingly, the proliferative capability of hepatocytes is severely impaired and extracellular matrix components are deposited to retrieve space lost by the destruction of hepatic parenchyma, resulting in the establishment of liver cirrhosis.

Usefulness of liver infiltrating CD86-positive mononuclear cells for diagnosis of autoimmune hepatitis.

AIM: Although the pathogenic mechanism underlying autoimmune hepatitis (AIH) remains unclear, the immune system is thought to be critical for the progression of the disease. Cellular immune responses may be linked to the hepatocellular damage in AIH. Recently, much attention has been focused on the critical functions of costimulatory molecules expressed on mononuclear cells in the generation of effective T cell-mediated immune responses. Analysis of costimulatory molecule expressed on mononuclear cells from the patients with AIH may give us insight into the pathogenic mechanism of hepatocellular damage in AIH. METHODS: Peripheral blood mononuclear cells (PBMC) were taken from the patients with AIH (34 cases) and healthy controls (25 cases). Liver infiltrating mononuclear cells (LIMCs) were taken from the patients with AIH (18 cases), the patient with chronic hepatitis C (CH-C) (13 cases) and the patients with fatty liver (2 cases). Using flow cytometry, the cells were analyzed for the expression of costimulatory molecules, such as CD80, CD86, and CD152 (CTLA-4). The results were compared with clinical data such as the level of gammaglobulin, histological grade, presence or absence of corticosteroids administration and the response to corticosteroids. RESULTS: The levels of CD80+, CD86+ and CD152+ PBMC were significantly reduced in the patients with AIH as compared with healthy controls. By contrast, those cells were significantly higher in LIMC than in PBMC of the patients with AIH. Especially, the level of CD86+ LIMC showed a marked increase irrespective of the degree of disease activity in the patients with AIH, although CD86+ cells were rarely present in PBMC. The levels of CD86+ cells were present in significantly higher frequency in patients with AIH than in the patients with CH-C. Furthermore, the patients with AIH with high levels of CD86+ LIMC showed good responses to corticosteroids, whereas 2 cases of AIH with low levels of CD86+ LIMC did not respond well. CONCLUSION: These results suggest that LIMC over-expressing costimulatory molecules such as CD80 and CD86 appears to play a role in the pathogenesis of AIH. Especially, CD86 molecule expressed on the LIMC may be useful for the diagnosis of AIH and for the prediction of the therapeutic effects of corticosteroids on AIH.

Antitumor effects of vitamins K1, K2 and K3 on hepatocellular carcinoma in vitro and in vivo.

A number of studies have shown that various K vitamins, specifically vitamins K2 and K3, possess antitumor activity on various types of rodent- and human-derived neoplastic cell lines. In the present study, we examined the antitumor effects of vitamins K1, K2 and K3 on PLC/PRF/5 human hepatocellular carcinoma (HCC) cells in vitro and in vivo. Furthermore, we examined the mechanisms of antitumor actions of these vitamins in vitro and in vivo. Although vitamin K1 did not inhibit proliferation of PLC/PRF/5 cells at a 90-microM concentration (the highest tested), vitamins K2 and K3 suppressed proliferation of the cells at concentrations of 90 and 9 microM, respectively. By flow cytometric analysis, it was shown that not only vitamin K1, but also vitamin K2 did not induce apoptosis or cell cycle arrest on PLC/PRF/5 cells. In contrast, vitamin K3 induced G1 arrest, but not apoptosis on PLC/PRF/5 cells. Subsequent in vivo study using subcutaneous HCC-bearing athymic nude mice demonstrated that both vitamins K2 and K3 markedly suppressed the growth of HCC tumors to similar extent. Protein expression of cyclin D1 and cyclin-dependent kinase 4 (Cdk4), but not p16INK4a Cdk inhibitor in the tumor was significantly reduced by vitamin K2 or K3 treatment, indicating that vitamins K2 and K3 may induce G1 arrest of cell cycle on PLC/PRF/5 cells in vivo. Taken collectively, vitamins K2 and K3 were able to induce potent antitumor effects on HCC in vitro and in vivo, at least in part, by inducing G1 arrest of the cell cycle. The results indicate that vitamins K2 and K3 may be useful agents for the treatment of patients with HCC.

Enhanced expression of p46 Shc in the nucleus and p52 Shc in the cytoplasm of human gastric cancer.

Shc protein is known to be related to cell proliferation and carcinogenesis. However, the involvement of Shc in gastric cancer remains unknown. In the present study, we examined the expression and localization of Shc in human gastric cancer and the adjacent normal mucosa by Western blotting and immunohistochemical analyses. Furthermore, the expression of Shc in a gastric cancer cell line, MKN 28, was also studied. p66 Shc was not detected at all in gastric cancer or the adjacent normal mucosa. In contrast, immunohistochemical and Western blot analyses revealed that p52 Shc was detected in the cytoplasmic fractions obtained from gastric normal mucosa and cancer, while p46 Shc expression was observed in the nuclear fractions from gastric normal mucosa and cancer. Furthermore, not only p52 Shc expression in the cytoplasm but also p46 Shc expression in the nucleus was much higher in gastric cancer than in the adjacent normal mucosa. Subsequent in vitro experiments with MKN 28 gastric cancer cells also revealed that p52 Shc was expressed solely in the cytoplasm and p46 Shc was solely in the nucleus. These results suggest that the enhancement of p46 Shc and p52 Shc expression may be related to the occurrence of gastric cancer. Furthermore, unlike p52 Shc, p46 Shc was shown to be expressed solely in the nucleus, suggesting that p46 Shc expressed in the nucleus may play an important role in gastric carcinogenesis.

Comparison study of the expressions of myristoylated alanine-rich C kinase substrate in hepatocellular carcinoma, liver cirrhosis, chronic hepatitis, and normal liver.

The myristoylated alanine-rich C kinase substrate (MARCKS) is a prominent substrate for protein kinase C (PKC) in a variety of cells. The aim of this study was not only to evaluate the expression and localization of MARCKS in various pathological liver tissues, including HCC, but also to analyze the difference in MARCKS expression between hepatitis virus-induced HCC and cirrhosis. The level of MARCKS and its phosphorylated proteins, as well as its localization, were determined using Western blot and/or immunohistochemistry in HCC and other pathological liver tissues. We also analyzed the change of MARCKS localization on the influence of MARCKS phosphorylation in the HLF cancer cell line by phosphorylation study. In addition, the relationship between MARCKS expression and proliferative activity was studied in HCC. In the immunohistochemical study, a very small amount of MARCKS protein was found along the contour of the hepatocellular membrane in normal liver and in cases of chronic hepatitis. MARCKS was up-regulated in liver cirrhosis tissue and was localized in the cytoplasm of hepatocytes. The expression of MARCKS was down-regulated in HCC tissues, as compared with non-tumorous liver cirrhosis tissues from the same patients. Furthermore, MARCKS was serine-phosphorylated in liver cirrhosis and HCC, and phosphorylated MARCKS was detected in a cytosolic fraction of these tissues. In a phosphorylation study using the HLF HCC cell line, MARCKS was displaced from the plasma membrane to the cytosol following the activation of protein kinase C (PKC) by phorbol 12-myristrate 13-acetate (PMA). Furthermore, the activity of cyclin D1 and cyclin E kinases was found to be higher in HCCs with low MARCKS expression than in HCCs with high MARCKS expression. These results suggest that up-regulation of MARCKS might be essential in the generation of cirrhotic nodules through chronic hepatitis from normal liver, and that the phosphorylation and/or down-regulation of MARCKS might play an important role in the development and progression of HCC from liver cirrhosis.

Estimation of the stent placement above the intact sphincter of Oddi against malignant bile duct obstruction.

BACKGROUND: In endoscopic biliary stenting against malignant biliary obstruction, stent blockage remains as an important problem. Stent blockage occurs as a result of bacterial adherence to the inner wall of the stent. We evaluated the stent placement above the intact sphincter of Oddi to retain the function of the sphincter of Oddi as a bacteriological barrier. METHODS: Sixteen patients with malignant biliary obstruction were assessed as the patients with the stent above the intact sphincter of Oddi. Sixteen patients with malignant biliary obstruction were assessed as the patients with the conventional stent placement across the sphincter of Oddi. Tannenbaum 10-Fr. stents were used in both the groups. RESULTS: The median patency periods of the stent were 255 days (25th to 75th percentiles, 212-454 days; range, 39-454 days) for the group of the stents placed above the sphincter of Oddi and 82 days (25th to 75th percentiles, 48-131 days; range, 22-196 days) for the group of the stents placed across the sphincter of Oddi, respectively, with significant difference (P = 0.0001). The occlusion rates of stents placed above and across the sphincter of Oddi were 37.5% and 93.8%, respectively, with significant difference (P = 0.0008). The dislocation rates of the stent were 0% and 6.3%, respectively (not significant). CONCLUSIONS: Placement of the stent above the intact sphincter of Oddi was associated with longer stent patency and lower occlusion rate.

Diffuse large B-cell primary gastric lymphoma treated successfully with the CD20 monoclonal antibody (rituximab): a case with severe liver dysfunction due to liver cirrhosis and hepatocellular carcinoma.

Primary gastric lymphoma is relatively rare in the scope of gastric malignancies. Here we report a case of diffuse large B-cell primary gastric lymphoma treated successfully with the CD20 monoclonal antibody, rituximab, alone. Because the patient had a complication of severe liver dysfunction due to hepatitis C virus induced-liver cirrhosis and hepatocellular carcinoma, it was difficult to treat the primary gastric lymphoma using standard therapy such as surgical resection and cocktail chemotherapy. Therefore, rituximab was administered to the patient, resulting in complete remission of the primary gastric lymphoma. This case indicates that monotherapy using only rituximab may be a promising option for the treatment of patients with diffuse large B-cell lymphoma accompanied by severe liver dysfunction.

Adenovirus-mediated gene transfer into rat livers: comparative study of retrograde intrabiliary and antegrade intraportal administration.

To examine the feasibility of liver-directed in vivo gene therapy, we administered recombinant adenoviruses carrying a reporter lacZ gene retrogradely into the common bile duct of rats, as well as antegradely into the portal vein. Transduction efficiency of the lacZ gene in the liver was estimated not only histochemically by X-gal staining, but also quantitatively by a chemiluminescent reporter gene assay. Retrograde infusion of adenoviruses into the common bile duct was shown to successfully induce transgene expression in the liver. Transduction efficiency induced by intrabiliary adenoviral administration was not significantly different from that induced by intraportal adenoviral administration. Although transgene expression induced not only by intraportal, but also by intrabiliary adenoviral administration was observed predominantly at periportal areas, a considerable number of cells expressing the transgene were detectable even in lobular and centrilobular areas. Mild infiltration of inflammatory cells into the liver and mild hyperplastic changes of hepatocytes were observed after intrabiliary and intraportal adenoviral administration. However, hepatic damage estimated pathologically was not substantial. Furthermore, although intrabiliary and intraportal adenoviral administration resulted in very mild elevation of liver-related serum biochemical parameters, apparent complications were not observed in any rats. Our results demonstrated in the present study suggest that retrograde administration of adenoviruses into the common bile duct can induce efficient transgene expression in the liver without causing severe adverse effects, supporting the feasibility of adenovirus-mediated gene transfer into the liver in clinical settings by means of endoscopic retrograde cholangiography.

Successful laparoscopic radiofrequency ablation of hepatocellular carcinoma adhered to the mesentery after transcatheter arterial embolization.

A 54-year-old male with hepatocellular carcinoma (HCC) underwent transcatheter arterial embolization (TAE) at a nearby hospital. He was then referred to our hospital for the purpose of additional treatment of HCC. Because TAE was not a complete therapy and HCC was growing and protruding from the left lobe of the liver, laparoscopic radio-frequency ablation (RFA) was chosen for the treatment of HCC. After inserting a laparoscope into the abdominal cavity, it was observed that HCC unexpectedly adhered to the mesentery as a result of TAE performed previously. After cutting off the adhered mesentery and removing it from the tumor, the combination therapy of percutaneous ethanol injection and RFA (PEI-RFA), developed at our department, was performed on the tumor. The tumor was successfully abrogated by PEI-RFA and the sufficient safety margin was confirmed by computed tomography after the treatment.