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With the aging of the population and rising incidence of thromboembolic events, the usage of antiplatelet agents is also increasing. There are few reports yet on the management of antiplatelet agents for patients undergoing colorectal endoscopic submucosal dissection (ESD).The aim of this study is to evaluate whether continued administration of antiplatelet agents is associated with an increased rate of delayed bleeding after colorectal ESD.A total of 1022 colorectal neoplasms in 927 patients were dissected at Yokohama City University Hospital and its three affiliate hospitals between July 2012 and June 2017. We included the data of 919 lesions in the final analysis. The lesions were divided into three groups: the no-antiplatelet group (783 neoplasms), the withdrawal group (110 neoplasms), and the continuation group (26 neoplasms).Among the 919 lesions, bleeding events occurred in a total of 31 (3.37%). The rate of bleeding after ESD was 3.3% (26/783), 4.5% (5/110), and 0% (0/26), respectively. There were no significant differences in the rate of bleeding after ESD among the three groups (the withdrawal group vs. the no-antiplatelet group, the continuation group vs. the no-antiplatelet group, and the withdrawal group vs. the continuation group).Continued administration of antiplatelet agents is not associated with any increase in the risk of delayed bleeding after colorectal ESD. Prospective, randomized studies are necessary to determine whether treatment with antiplatelet agents must be interrupted prior to colorectal ESD in patients who are at a high risk of thromboembolic events.

Endoscopic submucosal dissection (ESD) for early-stage colorectal cancer (CRC) has become a common and useful treatment. Although sarcopenia has been identified as an independent risk factor for complications after surgery for CRC, whether sarcopenia is also an independent risk factor for complications after colorectal ESD remains to be clarified. The aim of this study was to compare the outcomes of colorectal ESD in patients with and those without sarcopenia. This is a retrospective cohort study. A total of 334 patients underwent colorectal ESD for 361 neoplasms at Hiratsuka City Hospital from March 2012 to October 2018. The neoplasms were divided into two groups depending on the presence or absence of sarcopenia in the patients. Overall, 334 patients underwent colorectal ESD for 361 neoplasms during the study period. We excluded 90 patients (90 neoplasms), and 244 patients (277 neoplasms) were included in the final analysis (134 from the sarcopenia group, 137 from the non-sarcopenia group). The en-bloc resection rate was high and was not significantly different between the sarcopenia group [126/134 (94.1%)] and the non-sarcopenia group [133/137 (97.1%)], P = 0.1778). The rate of perforation and the rate of delayed bleeding were not significantly different between the sarcopenia group and the non-sarcopenia group [6/134 (4.5%) vs. 9/137 (6.6%), P = 0.314, 4/134 (3%) vs. 6/137 (4.4%), P = 0.3885, respectively]. The presence of sarcopenia did not influence the rate of complications after ESD. Colorectal ESD is safe and effective even in patients with sarcopenia. Prospective multicenter studies are necessary to confirm our results.

Background/Aims The aim of this study was to examine the convenience of the quality of life and utility evaluation survey technology (QUEST) questionnaire and the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG) questionnaire as self-assessment diagnostic instrument. Methods This was a two-way crossover study conducted over 6 weeks from September 2010 to November 2010. The subjects were 60 consecutive patients admitted to the Hiratsuka city hospital with a gastrointestinal condition, regardless of the coexistence of heartburn. They were assigned to fill in both the QUEST and FSSG questionnaires in random order. We analyzed the time taken to complete the questionnaires, whether subjects asked any questions as they filled in the questionnaire, and the questionnaire scores. Results Comparison of the QUEST and the FSSG revealed significant differences in the completion time (196.5 vs. 97.5 seconds, respectively; P < 0.0001) and in whether subjects asked any questions (37 vs. 15 subjects, respectively; P < 0.0001). Completion time in QUEST scores of ≥ 4 was lower than < 4 (170.5 vs. 214.0 seconds, respectively; P = 0.022), and the QUEST score was significantly higher without questions than with question (3 vs. 1 points, respectively; P = 0.025). Conclusions This study revealed that the FSSG questionnaire may be easier for Japanese subjects to complete than the QUEST questionnaire.

Aim In this multicenter, randomized trial, we evaluated the effectiveness of meloxicam – a non-steroidal anti-inflammatory drug – as an adjuvant for enhancing antiviral efficacy and preventing neutropenia during the treatment of patients with genotype 1 chronic hepatitis C using peginterferon and ribavirin. Methods A total of 60 patients were randomly assigned, in a 1:1 ratio, to either the meloxicam or the control group after stratification by neutrophil count. Both groups received weekly peginterferon-α-2a (180 μg) and a weight-based dose of ribavirin for 48 weeks. The meloxicam group received meloxicam (10 mg/day) for the first 8 weeks after initiation of treatment. Results Through intent-to-treat analysis, we found that the sustained virological response rate in the meloxicam group (19/30, 63.3%) was significantly higher than in the control group (11/30, 36.7%, P

Aim: The optimal ribavirin dose in the treatment of patients infected with hepatitis C virus (HCV) genotype 2 remains to be elucidated. We aimed to seek the optimal ribavirin dose required for this genotype in a randomized trial. Methods: We compared the efficacy and tolerability of the 24-week peginterferon α-2b (1.5 µg/kg/week) therapy in combination with a weight-based higher dose (600–1000 mg) and lower dose (400–800 mg) of ribavirin for genotype 2 patients. Noninferior margin was set at 10%. Results: A total of 120 patients were randomized to a higher-dose or a lower-dose group. Sustained virological response (SVR) by intention-to-treat analysis was achieved in 47/58 (81.0%, 90% confidential interval [CI]: 72.6–89.5) patients in the higher-dose group and 41/60 (68.3%, 90% CI: 58.5–78.2) patients in the lower-dose group (difference, −12.7%; 90% CI, −25.7 to 0.3). Relapse rates were 10% and 21.6% in the higher-dose and the lower-dose groups, respectively. Multiple logistic regression analysis showed that ribavirin dose/kg body weight was the only significant predictor of SVR (≥9.5 mg/kg per day vs

BACKGROUND/AIMS The effects of Histamine-2 receptor antagonists and proton pump inhibitors on the gastrointestinal motility have not yet been sufficiently investigated. The aim of this study was to determine the effects of intravenous bolus administration of famotidine and omeprazole on the rate of gastric emptying using the continuous (13)C breath test (BreathID system, Exalenz Bioscience Ltd, Israel). METHODS Twelve healthy male volunteers participated in this randomized, 3-way crossover study. After fasting overnight, the subjects were randomly assigned to receive 20 mg of famotidine, 20 mg of omeprazole or 20 mL of saline alone by intravenous bolus injection before a test meal (200 kcal per 200 mL, containing 100 mg of (13)C-acetate). Gastric emptying was monitored for 4 hours after the ingestion of test meal by the (13)C-acetic acid breath test performed using the BreathID system. RESULTS No significant differences in the calculated parameters, namely, the T(1/2), T(lag), GEC, β and κ, were observed among the 3 test conditions. CONCLUSIONS The study revealed that intravenous administration of gastric acid suppressant drugs had no significant influence on the rate of gastric emptying in comparison with that of saline alone as a placebo. Our results indicating the absence of any effect of either famotidine or omeprazole on accelerating the rate of gastric emptying suggest that both medications can be administered safely to patients suffering from hemorrhagic peptic ulcers who need to be kept nil by mouth from the viewpoint of possible acceleration of gastrointestinal motility in the clinical setting.

肝細胞癌に対するラジオ波焼灼療法（以下RFA）後に，肝内に多発性に再発する症例が報告されている．我々は同区域多発再発した肝細胞癌に対し体幹部定位放射線治療（以下SBRT）を施行し，著効した症例を経験したので報告する．症例は77歳男性．2002年1月に肝S6の腫瘤を認めた．同年2月に腫瘍生検を施行しNASH（非アルコール性脂肪肝炎）に合併した肝細胞癌と診断，同年3月にRFAを施行した．2004年9月に肝S6に同区域多発再発病変が認められたため，線量35 Gy/5回/1週間にてSBRTを施行した．SBRT後，CTにて再発病変は消失し，PIVKA-IIも262 mAU/mlから29 mAU/mlと正常に復した．多発性の再発病変も病巣範囲がある程度限局していれば，SBRTによりコントロール可能となることもあり，本症例を通じRFA後の同区域多発再発病変に対してSBRTは検討すべき治療法の一つであることが示唆された．

AIM: To investigate the efficacy and toxicity of hypofractionated stereotactic radiotherapy for the treatment of patients presenting with hepatocellular carcinoma (HCC) in a single institutional setting. METHODS: Sixteen patients who presented with solitary HCC, including two patients with a tumor thrombus of the portal veins, were treated with stereotactic radiotherapy with or without transarterial chemoembolization. The criteria for stereotactic radiotherapy were existence of technical difficulties for other ablation therapies, inoperable disease or refusal to undergo surgery, tumor staged as Grade A or B according to the Child-Pugh classification, and solitary tumor distant from the gastrointestinal tract and kidney with a tumor volume

We have isolated two stable human bcl-2 transfected cell lines, HCC-T-bcl and PLC-bcl, that were derived from the transfection of two human hepatocellular carcinoma cell lines (HCC-T and PLC/PRF/5, respectively) with a plasmid vector containing recombinant bcl-2 (pCAGGS-bcl).) Cell lines transfected with the plasmid alone (pCAGGS-neo) were also established as controls (HCC-T-neo and PLC-neo). HCC-T-neo and PLC-neo were sensitive to doxorubicin-induced apoptosis, as defined by morphological observation. Although HCC-T-neo expressed endogenous Bcl-2, the sensitivity of HCC-T-neo to doxorubicin-induced cytotoxicity was similar to that of PLC-neo, which does not express endogenous Bcl-2. In contrast, both HCC-T-bcl and PLC-bcl were more resistant to doxorubicin-induced cytotoxicity. Although these bcl-2 transfectants were resistant to the drug-induced apoptosis, Bcl-2 overexpression did not affect doxorubicin-induced growth suppression. These results suggest that the overexpression of Bcl-2 renders human HCC cells resistant to doxorubicin-induced cytotoxicity.

To investigate the effects of T-helper cytokines on Kupffer cells (KCs), the effects of interferon-gamma (IFN-gamma; Th1 cytokine) and interleukin-4 (IL-4; Th2 cytokine) on KC morphology and their role in modulating the growth of hepatic stellate cells (HSCs) were examined. Fluorescence microscopic and electron microscopic data demonstrated that IL-4 transforms rat KCs into multinucleated giant cells (MGCs) in vitro. This transformation was inhibited by the addition of anti-ICAM-1 and anti-CD18 monoclonal antibodies. In addition, IL-4-induced KC transformation was suppressed by the presence of IFN-gamma. The formation of mouse hepatic MGCs was also demonstrated in vivo by the intraperitoneal injection of recombinant mouse IL-4. Although the presence of MGCs was found in all five out of five livers from IL-4-treated Th2-dominant BALB/c mice, but it was in only two out of five livers from IL-4-treated Th1-dominant C57BL/6 mice. In addition, fewer MGCs were found in the liver of C57BL/6 mice. In contrast, IFN-gamma treatment did not form hepatic MGCs in mice at all. The growth of HSCs in vitro was significantly increased by the addition of culture supernatant from lipopolysaccharide-stimulated rat KCs. Pretreatment of the KCs with either IFN-gamma or IL-4 further enhanced the growth stimulation. These results suggest that IFN-gamma and IL-4 affect KC morphology differently, but that both Th1 and Th2 cytokines play a similar role in the modulation of HSC growth by Kupffer cells in the presence of lipopolysaccharide.

Effects of interleukin-4 (IL-4) and interferon-γ (IFN-γ) on rat Kupffer cell (KC) functions were investigated. Lipopolysaccharide (LPS)-stimulated KCs pretreated with IL-4 produced much more prostaglandin E 2 than those pretreated with IFN-γ. In contrast, LPS-stimulated KCs pretreated with IFN-γ produced much more tumor necrosis factor-α, and nitrate and nitrite than those pretreated with IL-4. Different morphologic changes were induced after the culture with each cytokine; transformation of KCs into multinucleated giant cells with IL-4 was especially noted. These results suggest that IFN-γ and IL-4, produced by different subsets of T-helper lymphocytes, differently induce KC into specific morphology, and change KC response to endotoxins, possibly resulting in a modulation of hepatic inflammation.

We have reported the Keio multicenter randomized trial of interferon-a2b treatment for chronic hepatitis C, hypothesizing that disappearance of serum hepatitis C virus (HCV) ribonucleic acid (RNA) during the first 2 days by one dose administration of interferon is a predictive factor of final response to the high-dose interferon treatment. In this study we quantified HCV RNA by multicyclic reverse transcription-polymerase chain reaction in the stored sera of the same patients with our previous study. The multivariate analysis confirmed that the pretreatment HCV RNA levels and HCV genotype were significantly correlated with the response to the 6-month course interferon treatment. Although the relationship between decreased HCV RNA titers within the first 2 days after one dose administration of interferon and the efficacy of the therapy was not obtained, the cases in which HCV RNA disappeared within 2 days significantly responded to the 6-month course treatment (73.7% vs 12.5% in other cases, p

A gene encoding the variable regions of the heavy and light chains of a mouse monoclonal antibody designated H2, which specifically reacts with human liver cells, was cloned into a phagemid vector. The clone of the variable region was designed to be expressed as a separate protein, the structure of which is the same as that of the mouse antibody. The cloned phage protein specifically reacted with anti-idiotypic antibodies produced in rabbits against the original mouse antibody, and this reaction was specifically blocked by the original antibody. The soluble protein, expressed as a fusion protein, was detected as a single 30-kd band on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and specifically bound to an anti-H2 idiotypic antibody as determined by Western blot analysis. Sera of patients with various diseases were assayed for antibodies to anti-H2 by sandwich enzyme-linked immunosorbent assay (ELISA). Only sera from patients with chronic liver disease reacted strongly. This binding was specifically blocked by the cloned soluble protein. The nucleotide sequences of the variable regions were determined by the dideoxy chain-termination method, and the sequences were approximately 95% identical to those of other mouse immunoglobulins. These findings suggest that a human antibody with the same idiotype as a mouse monoclonal antibody that reacts with human liver cells, can be detected in patients with chronic liver disease, suggesting that autoimmunity may be partly responsible for these diseases.

A combined preparation of liver extract and flavin adenin dinucleotide (FAD) (Adelavin) has been widely used in patients with chronic liver diseases in Japan. One milliliter of this agent contains 15 microliters of phenol-soluble phase of liver nucleic acid fraction and 10 mg of FAD. To examine the advantages of using this preparation in the elimination of hepatitis C virus (HCV) from patients with chronic hepatitis (CH)-C receiving interferon (IFN), 2 ml of this preparation was intravenously (n = 9) or intramuscularly (n = 8) administered daily for 5 days before 6 million units of IFN-alpha was intramuscularly injected once. Before and 48 hours after the injection of IFN, serum ALT, 2'5'-oligoadenylate synthetase (2'5-AS) activity, and HCV RNA levels were measured. The daily administration of this preparation alone for 5 days did not significantly change serum ALT, 2'5-AS activities, and HCV RNA levels. The 2'5-AS activities were significantly increased by IFN after the intravenous injection of this preparation (p0.01), while an injection of IFN alone of this dose did not change its activities (n = 10). HCV RNA levels were significantly decreased by IFN only after the administration of the preparation (intramuscular, p0.01; intravenous, p0.01). The effect of intravenous injection of this preparation was also elicited in patients with HCV genotype II and with HCV more than 10(5) copies/ml. These results suggest that this preparation may enhance the 2'5-AS production by IFN as a result of the increase in mitochondrial adenosin triphosphate production and may be a potent agent to enhance the anti-viral efficacy of IFN in patients with CH-C.

Rat Kupffer cell (KC)-mediated cytotoxicity against both the syngeneic hepatoma cell line AH70 and hepatocytes was evaluated by changes in mitochondrial function, and the possible role of ICAM-1/CD18 in the interaction between the cells was studied. Rhodamine 123 fluorescence, a marker of the mitochondrial membrane potential, decreased in AH70 cells after co-culture with CK, while that in hepatocytes was unchanged by co-culture. This decrease was blocked by anti-ICAM-1 anti-CD18 and the inhibition of nitric oxide synthesis. Cytometric studies demonstrated that ICAM-1 expression on AH70 cells increased after addition of IFN-gamma, IL-1beta, tumor necrosis factor (TNF)-alpha or KC, while in hepatocytes ICAM-1 was not increased. Anti-ICAM-1 pretreatment inhibited the increase in ICAM-1 expression and the decrease in rhodamine 123 fluorescence on AH70 cells after co-culture with KC. CD18 on KC was increased only after co-culture with AH70. TNF-alpha but not IFN-gamma was detected in the supernatant of co-culture between KC and AH70 cells, and this production was partially inhibited by anti-ICAM-1 and anti-CD18. The activity of inducible nitric oxide synthase in Kupffer cells and the levels of nitrites and nitrates in the co-culture supernatant increased over time, and this increase was attenuated either by addition of NO synthesis inhibitors, anti-ICAM-1 or anti-CD18. These results indicate that the rat KC causes mitochondrial dysfunction in cancer cells via the production of NO and cell-to-cell adhesion via ICAM-1/CD18 has an important role in this cytotoxic process.

ADH/GPT比が高値を示した成人発症Still病(AOSD)の2例を報告する.症例1は30歳女性.39℃台の弛張熱,発疹および関節痛を主訴に当院を受診.GOT 133IU/l, GPT 417IU/l, LDH 514IU/lと肝機能障害が認められ入院した.ADH/GPT比が高値を示し,さらに急性期の肝生検像で,中心静脈周囲に限局した肝細胞壊死が確認された.症例2は重症肝障害および播種性血管内血液凝固症を合併した44歳女性.ADH/GPT比が高値を示した.いずれの症例も副腎皮質ステロイド薬が著効し軽快した.これらAOSD 2例における肝障害の主座は中心静脈領域であることが示され,さらに血清ADH活性測定は肝障害の鑑別にも有用と考えられた.

In this multicenter, randomized trial, we evaluated the effectiveness of meloxicam - a non-steroidal anti-inflammatory drug - as an adjuvant for enhancing antiviral efficacy and preventing neutropenia during the treatment of patients with genotype 1 chronic hepatitis C using peginterferon and ribavirin.A total of 60 patients were randomly assigned, in a 1:1 ratio, to either the meloxicam or the control group after stratification by neutrophil count. Both groups received weekly peginterferon-α-2a (180 μg) and a weight-based dose of ribavirin for 48 weeks. The meloxicam group received meloxicam (10 mg/day) for the first 8 weeks after initiation of treatment.Through intent-to-treat analysis, we found that the sustained virological response rate in the meloxicam group (19/30, 63.3%) was significantly higher than in the control group (11/30, 36.7%, P 0.05). The relapse rate was more than twice as high (45%) in the control group than in the meloxicam group (19.0%); however, this difference was not statistically significant. The rate of neutrophil decrease, calculated by dividing the lowest value observed during the first 8 weeks by pretreatment count, was significantly smaller in the meloxicam group (55.1 ± 14.3%) than in the control group (62.3 ± 9.6%, P 0.05).Meloxicam enhanced antiviral efficacy and reduced the decline in neutrophil counts for the peginterferon and ribavirin treatment of genotype 1 chronic hepatitis C. This drug could be a reasonable adjuvant for the treatment of patients with chronic hepatitis C. The present study including a small number of patients warrants larger clinical trials.

The optimal ribavirin dose in the treatment of patients infected with hepatitis C virus (HCV) genotype 2 remains to be elucidated. We aimed to seek the optimal ribavirin dose required for this genotype in a randomized trial. We compared the efficacy and tolerability of the 24-week peginterferon α-2b (1.5 µg/kg/week) therapy in combination with a weight-based higher dose (600-1000 mg) and lower dose (400-800 mg) of ribavirin for genotype 2 patients. Noninferior margin was set at 10%. A total of 120 patients were randomized to a higher-dose or a lower-dose group. Sustained virological response (SVR) by intention-to-treat analysis was achieved in 47/58 (81.0%, 90% confidential interval [CI]: 72.6-89.5) patients in the higher-dose group and 41/60 (68.3%, 90% CI: 58.5-78.2) patients in the lower-dose group (difference, -12.7%; 90% CI, -25.7 to 0.3). Relapse rates were 10% and 21.6% in the higher-dose and the lower-dose groups, respectively. Multiple logistic regression analysis showed that ribavirin dose/kg body weight was the only significant predictor of SVR (≥9.5 mg/kg per day vs9.5 mg/kg per day; odds ratio = 3.34; 95% CI, 1.41-7.92; P = 0.006). Twenty-one (36.2%) in the higher-dose group required ribavirin dose reduction because of anemia, whereas seven patients (11.7%) did in the lower-dose group (P 0.01). Three of the higher-dose group and two of the lower-dose group required premature termination of therapy. Weight-based lower-dose ribavirin regimen was not equivalent to the higher-dose counterpart in the treatment of HCV genotype 2. We discourage treating these patients with low-dose ribavirin regimens. The peginterferon therapy in combination with ribavirin at a weight-based higher dose (600-1000 mg) remains the standard-of-care treatment for this genotype.

Mucosal prolapse syndrome (MPS) has been recognized as a chronic benign inflammatory disorder, characterized mainly by rectal mucosal prolapse. Disorders representing this condition include solitary rectal ulcer syndrome (SRUS), rectal prolapse, proctitis cystica profunda, and inflammatory cap polyps. The gross appearance of rectal MPS can be occasionally misinterpreted as rectal cancer. In contrast, there have been a few reports of colorectal cancer originating from prolapsed mucosa. Herein, we report a case of MPS associated with two independent rectal cancers extending into the submucosal layer. We speculate that long-standing MPS may increase the risk of malignant transformation.

The aim of this study was to determine whether oral Itopride hydrochloride (itopride) intake might have any effect on the rate of gastric emptying, using a novel non-invasive technique for measuring the rate of gastric emptying, namely, the continuous real time 13C breath test (BreathID system: Exalenz Bioscience Ltd., Israel).Eight healthy male volunteers participated in this randomized, two-way crossover study. The subjects fasted overnight and were randomly assigned to receive 50mg itopride following a test meal (200 kcal per 200mL, containing 100mg 13C acetate), or the test meal alone. Under both conditions, gastric emptying was monitored for 4 hours after administration of the test meal by the 13C-acetic acid breath test performed continually using the BreathID system. Using Oridion Research Software (beta version), the time required for emptying of 50% of the labeled meal (T 1/2), the analog to the scintigraphy lag time for 10% emptying of the labeled meal (T lag), the gastric emptying coefficient (GEC), and the regression-estimated constants (beta and kappa) were calculated. The parameters measured under the two conditions were compared using the Wilcoxon's signed-rank test.No significant differences in the calculated parameters, namely, the T 1/2, T lag, GEC, beta or kappa, were observed between the two test conditions, namely, administration of a test meal+itopride and administration of the test meal alone.The present study revealed that postprandial itopride intake had no significant influence on the rate of gastric emptying. Recently, several studies have shown that itopride may be effective in the treatment of patients with functional dyspepsia. Our results suggest that the efficacy of itopride in patients with functional dyspepsia may be based on its effect of improving functions other than the rate of gastric emptying, such as the activities at neuronal sites, brain-gut correlation, visceral hypersensitivity, gastric accommodation and distension-induced adaptation.

Low-dose aspirin is widely used for the prevention of cardiovascular and cerebrovascular diseases. However, administration of low-dose aspirin is associated with an increased risk of upper gastrointestinal complications, such as upper gastrointestinal erosions, ulcers and bleeding. The aim of this study was to clarify the prevalence and various clinical factors of upper gastrointestinal complications associated with low-dose aspirin treatment.A total of 1213 patients taking low-dose aspirin were evaluated with upper endoscopic examinations. We studied retrospectively the incidence of and risk factors for upper gastrointestinal complications associated with low-dose aspirin use.Of the 1213 patients taking low-dose aspirin, 598 patients and 72 patients were found to have gastroduodenal erosions (57.3%) and peptic ulcers (5.9%), respectively. Of these 72 peptic ulcers, 27 were diagnosed as hemorrhagic ulcers. Previous ulcer history was identified as a risk factor for peptic ulcer and upper gastrointestinal bleeding during low-dose aspirin therapy. Upper gastrointestinal symptoms and no use of gastroprotective agents were also identified as risk factors for peptic ulcers. In this study, the use of a histamine-2 receptor antagonist was indicated as a protective factor for peptic ulcers.Low-dose aspirin therapy is associated with an increased risk of developing upper gastrointestinal complications. Administration of a histamine-2 receptor antagonist was effective for the prevention of low-dose aspirin induced peptic ulcers.

Peginterferon (PEG-IFN) and ribavirin (RBV) combination treatment for patients with chronic hepatitis C (CHC), infected by genotype-1 hepatitis C virus with high viral loads, results in a sustained viral response (SVR) in ~50%. However, a trend of decreasing SVR in the older patients has been reported. In the present study, we verified this trend of treatment efficacy in older patients using the propensity score (PS).We conducted a survey of 327 patients with CHC (genotype 1 and high viral loads) who were treated with PEG-IFN and RBV for 48 weeks. The SVR rate was compared between patients =60 and60 years of age. Because backgrounds of these patients differed considerably, we verified this efficacy between the older (n = 102) and younger (n = 102) patients matched for gender, body weight, platelets (PLT), and red blood cell (RBC) counts using PS.The total SVR rate was 42.9% (161/327); this rate decreased with increasing age and was lower in the older patients (≥60 years: 41.5%,60 years: 54.3%, P = 0.0245). Moreover, younger age was a significant factor for SVR. After correction by PS, the SVR in older patients remained significantly lower (≥60 years: 43.1%,60 years: 57.8%, P = 0.0497). In addition, RBC counts and hemoglobin (Hgb) concentrations, as well as RBV adherence in the older patients, decreased with this treatment, although there were no significant differences in pretreatment RBC and Hgb levels.The analysis using PS indicated that RBV adherence in the older patients decreased even if they did not have lower pretreatment RBC and Hgb levels.

We analyzed the clinical efficacy of pre-operative combination chemotherapy using docetaxel, cisplatin and S-1 for advanced gastric cancer. Four patients were enrolled and staging laparoscopy was performed. Patients received intravenous docetaxel and cisplatin (35 mg/m2) on day 1 and 15, and oral S-1 80 mg/m2 on day 1-14 every 4 weeks. Two patients received two courses of chemotherapy and two patients received three courses of chemotherapy. Neutropenia of more than grade 3 was found in 3 cases. All cases were PR on preoperative imaging. Curative operation was performed on three cases. Histological anti-tumor effect was judged to be grade 2 in 1 case and grade 1a in 3 cases. In the postoperative period, all patients received S-1-based adjuvant chemotherapy. The combination chemotherapy using docetaxel, cisplatin and S-1 plus operation was a candidate for the standard treatment strategy for advanced gastric cancer.

they are usually asymptomatic, several complications have been reported. A 78-year-old man was admitted to our hospital with high-grade fever (39.6°C) and jaundice. His laboratory data showed liver dysfunction and elevations of the white blood cell count and serum C-reactive protein concentration. Abdominal ultrasonography demonstrated dilated biliary ducts. Abdominal computed tomography (CT) revealed a diverticulum in the second part of the duodenum (●" Fig. 1). We suspected obstructive cholangitis. Endoscopic retrograde cholangiography (ERC) was performed. Gastrointestinal endoscopy revealed a periampullary diverticulum occupied by a yellow stone (●" Fig. 2). ERC showed no abnormalities (●" Fig. 3). Therefore, we made a diagnosis of biliary tract obstruction caused by an enterolith in the periampullary duodenal diverticulum. We performed successful endoscopic removal of the enterolith (●" Fig. 4). The extracted enterolith was oval-shaped, yellowish in color, measured approximately 3 cm in diameter, and had a hard outer rim with an irregular surface (●" Fig. 5). Separate layers within the wall were appreciated and there was no evidence of any nidus, such as a fruit pit. Infrared absorption spectrophotometry showed that the enterolith consisted mainly of deoxycholic acid (●" Fig. 6). Duodenal diverticula are commonly encountered and are generally regarded as clinically insignificant entities. They can, however, sometimes produce serious complications, including diverticulitis, perforation, hemorrhage, biliary and/or pancreatic obstruction, partial duodenal obstruction, fistula formation with adjacent organs, diarrhea secondary to blind loop syndrome, and enterolith formation [1]. Enterolith formation is known to occur within regions of stasis, such as Meckel’s diverticulum or a blind loop, or as a result of stricture due to Crohn’s disease or tuberculosis. Duodenal diverticula may also represent such a region of stasis [2]. In conclusion, we performed successful endoscopic removal of an enterolith in a duodenal diverticulum. Obstructive cholangitis caused by an enterolith in a periampullary diverticulum is rare, but is an important entity for endoscopists.

The aim of this study was to clarify the prevalence and various clinical factors of upper gastrointestinal bleeding (UGIB) associated with low-dose aspirin (LDA) treatment.There were 6,807 patients who were under treatment with LDA at our hospital between January 2003 and November 2007. They had kept taking the LDA or started treatment in the study period and kept taking the whole period of observation. Esophagogastroduodenoscopy (EGD) was performed 453 patients of these patients, and 71 were diagnosed as LDA-associated UGIB. We examined the prevalence and various clinical factors of UGIB associated with LDA treatment.The occurrence rate of UGIB was 0.209 UGIB per 100 patient-years at least. The multivariate odds ratio of LDA-associated UGIB was 3.318 (95% confidence interval (CI) 1.650-6.671, p = 0.0008) for a history of peptic ulcer, 0.086 (95% CI: 0.011-0.652, p = 0.0176) for the use of a proton pump inhibitor (PPI) with LDA, and 0.253 (95% CI: 0.113-0.569, p = 0.0009) for the use of a histamine type 2 receptor antagonist (H2RA) with LDA.Our results suggest that a history of peptic ulcer significantly increases the risk of LDA-associated UGIB. Regular use of a PPI or a H2RA effectively decreases the risk.

To clarify the impact of adherence, we treated 122 genotype 1 high viral titer chronic hepatitis C patients with pegylated interferon (peg-IFN) and ribavirin for 48 weeks at nine referral hospitals, and evaluated the prognostic factors with a focus on the adherence to the treatment. This study included 68 (55.7%) treatment-naïve patients and 54 (44.3%) patients who did not respond to the previous treatment. Multivariate analysis revealed adherence to peg-IFN and ribavirin as the only significant predictor. Sustained virological response (SVR) rate was 72.2%, 19.0%, and 27.3% in patients given ≥80%, 60%–80%, and

A highly sensitive second-generation hepatitis C virus (HCV) core antigen assay has recently been developed. We compared viral disappearance and first-phase kinetics between commercially available core antigen (Ag) assays, Lumipulse Ortho HCV Ag (Lumipulse-Ag), and a quantitative HCV RNA PCR assay, Cobas Amplicor HCV Monitor test, version 2 (Amplicor M), to estimate the predictive benefit of a sustained viral response (SVR) and non-SVR in 44 genotype 1b patients treated with interferon (IFN) and ribavirin. HCV core Ag negativity could predict SVR on day 1 (sensitivity = 100%, specificity = 85.0%, accuracy = 86.4%), whereas RNA negativity could predict SVR on day 7 (sensitivity = 100%, specificity = 87.2%, accuracy = 88.6%). None of the patients who had detectable serum core Ag or RNA on day 14 achieved SVR (specificity = 100%). The predictive accuracy on day 14 was higher by RNA negativity (93.2%) than that by core Ag negativity (75.0%). The combined predictive criterion of both viral load decline during the first 24 h and basal viral load was also predictive for SVR; the sensitivities of Lumipulse-Ag and Amplicor-M were 45.5 and 47.6%, respectively, and the specificity was 100%. Amplicor-M had better predictive accuracy than Lumipulse-Ag in 2-week disappearance tests because it had better sensitivity. On the other hand, estimates of kinetic parameters were similar regardless of the detection method. Although the correlations between Lumipulse-Ag and Amplicor-M were good both before and 24 h after IFN administration, HCV core Ag seemed to be relatively lower 24 h after IFN administration than before administration. Lumipulse-Ag seems to be useful for detecting the HCV concentration during IFN therapy; however, we still need to understand the characteristics of the assay.

We studied hepatic stellate cell proliferation in vitro. Peripheral blood mononuclear cells (PBMC) from patients with chronic active hepatitis C (CAH) and liver cirrhosis (LC) were cultured for 24h in the presence or absence of Escherichia coli lipopolysaccharides (LPS). Hepatic stellate cell proliferation induced by the culture supernatants was measured, and interleukin-1 (IL-1) and IL-6 levels in the culture supernatants were quantified. Culture supernatants of LPS-stimulated PBMC from LC patients induced rat hepatic stellate cell proliferation by almost 2.8-fold (stimulation index, 2.83 +/- 1.41) compared with when the cells were cultured without addition of PBMC culture supernatants. Production of IL-1beta was significantly higher in the culture supernatants of both CAH and LC patients than in those of ten healthy controls (P < 0.01 and P < 0.05, respectively). But there was no significant correlation between IL-1 production and the induction of hepatic stellate cell proliferation by the culture supernatants. Although there were no significant differences in IL-6 production by LPS-stimulated PBMC among healthy controls and CAH and LC patients, we observed a significant correlation between IL-6 production and the induction of hepatic stellate cell proliferation in the culture supernatants of LC patients. Rat hepatic stellate cells themselves produced IL-6, and treatment with IL-6 antisense oligodeoxynucleotides suppressed the cell proliferation, suggesting that IL-6 is an autocrine growth factor for hepatic stellate cells. The addition of human recombinant IL-6 (hrIL-6) augmented rat hepatic stellate cell proliferation, indicating that excessive IL-6 may further facilitate cell proliferation. These findings suggest that a cytokine cascade including IL-6 may participate in hepatic stellate cell proliferation in LC patients when they are exposed to endotoxin.

Human E-cadherin is a homophilic cell adhesion molecule and its expression is well preserved in normal human hepatocytes; a decrease in its expression has been observed in poorly differentiated hepatocellular carcinoma cells. We examined the alteration of E-cadherin and catenin expressions caused by differentiation inducers in human hepatocellular carcinoma cells. Hepatocellular carcinoma cell lines, HCC-T and HCC-M, were cultured with all-trans retinoic acid (ATRA), dexamethasone (DEX), sodium butyrate, and interferon-alpha. E-cadherin expression was only up-regulated by butyrate and interferon-alpha (IFN-alpha) in both cell lines, studied by means of fluorescence immunostaining and flow cytometry. The localization of E-cadherin staining was shown at their cell membrane. According to the increase in E-cadherin expression, beta-catenin expression appeared at the cell membrane of both cell lines when treated with butyrate and IFN-alpha. Such an appearance was not observed when cells were treated with ATRA and DEX. Western blotting showed that alpha- and y-catenin expression was not changed, while only the expression of beta-catenin increased. Beta-catenin oncogenic activation as a result of amino acid substitutions or interstitial deletions within or including parts of exon 3, which has been demonstrated recently, was not detected in these cell lines by direct deoxyribonucleic acid sequencing. These results suggest that the expression and interaction between E-cadherin and wild-type beta-catenin are potentially modulated by butyrate and IFN-alpha, and that these two agents are potent inhibitors of hepatocellular carcinoma cell invasion and metastasis.

Background Spontaneous rupture is rare complication of hepatocellular carcinoma (HCC) with high mortality rate in cirrhotic cases. The aim of this study was to determine the factors influencing prognosis in cases of spontaneously ruptured HCC and to investigate the outcomes of the treatments employed, especially transcatheter arterial embolization (TAE). Methods A retrospective multicenter study was conducted in 48 cirrhotic patients with spontaneous rupture of HCC. Conservative treatment was employed in 32 patients (ConT group) and TAE was performed in 16 patients (TAE group). Results The median survival time (MST) in the ConT group was only 13.1 days and the survival rate was extremely poor: 59.4% at 7 days, 37.5% at 14 days, and 6.3% at 30 days. On the other hand, the MST in the TAE group was 244.8 days and the survival rate was 87.5% at 1 month, 56.3% at 3 months, 23.4% at 12 months, and 15.6% at 24 months. According to the results of univariate analyses, factors associated with poor hepatic function and poor suitability for TAE was important determinants of short-term death (less than 3 weeks) among the patients (p < 0.05). On the other hand, among the patients in whom initial TAE was successfully performed (n = 15), a multivariate analysis showed that a maximum tumor size not exceeding 7 cm was the only independent factor determining long-term survival (p = 0.0130). Conclusion Despite the inherent limitations of this retrospective study, TAE appears to be a useful treatment strategy for cirrhotic patients with spontaneous HCC rupture, as it yielded a longer survival period compared with conservative treatment in patients with ruptured HCC. Among the patients with ruptured HCC in whom initial TAE was successfully performed, the maximum tumor size was an important factor influencing survival.