Satoshi Sobue

Th1/Th2 cytokine profiles and their relationship to clinical features in patients with chronic hepatitis C virus infection

Purpose. An imbalance in helper T-cell type 1 (Th1) and type 2 (Th2) cytokines is suggested to play an important role in the pathogenesis of chronic viral infections, but this issue is not resolved in patients with hepatitis C virus (HCV) infection. The aim of this study was to clarify the relationship between the balance of Th1 and Th2 cytokines and liver damage. Methods. We investigated cytokine levels in the peripheral blood and liver tissue of patients with chronic HCV infection (n = 59) by three different methods; we used flow cytometry to detect intracellular cytokines, and we measured cytokine titers in sera and in the supernatants of lymphocyte cultures with enzyme-linked immunosorbent assays (ELISAs). Results. In both CD4+ and CD8+ cells, interferon (IFN) γ-producing cell populations increased, while there was no difference in interleukin (IL)-10 production, indicating a shift to a Th1 cytokine profile with the progression of liver disease. With respect to the ratio of IFN-γ to IL-10, a correlation was found in CD4+ cells between peripheral blood and liver tissue (r = 0.98; P = 0.0011). Th1 cytokine was predominant in intrahepatic CD4+ cells, while it was predominant in peripheral blood CD8+ cells. Conclusions. These findings indicate a correlation between dominant Th1 response and disease activity and progression. In addition, we suggest that intrahepatic CD4+ T cells play a pathogenetic role in the hepatic injury of HCV infection.

The efficacy of transcatheter arterial embolization as the first‐choice treatment after failure of endoscopic hemostasis and endoscopic treatment resistance factors

Aim:  The aim of this retrospective study was to evaluate the efficacy of transcatheter arterial embolization (TAE) as the first‐choice treatment in patients with bleeding peptic ulcer after the failure of endoscopic hemostasis. An additional objective was to clarify endoscopic treatment resistance factors.

Efficacy of famotidine and omeprazole in healing symptoms of non-erosive gastro-oesophageal reflux disease: randomized-controlled study of gastro-oesophageal reflux disease

Background : The epidemiology and pathophysiology of non‐erosive gastro‐oesophageal reflux disease differs from erosive gastro‐oesophageal reflux disease. There is a possibility that non‐erosive gastro‐oesophageal reflux disease treatment requires a different regimen/approach but it is not yet acknowledged.

Efficacy of Contrast-enhanced Computed Tomography for the Treatment Strategy of Colonic Diverticular Bleeding.

OBJECTIVE Diverticular bleeding is the most common cause of acute lower gastrointestinal bleeding, and its incidence has recently increased. However, the treatment strategy of diverticular bleeding has not yet been established. The aim of the study was to investigate the efficacy of contrast-enhanced computed tomography (CECT) to determine the indication for urgent colonoscopy to achieve hemostasis. METHODS A total of 124 patients diagnosed with diverticular bleeding between 2012 and 2013 in our hospital were analyzed. The clinical behavior, factors related to detecting bleeding diverticula, and risk factors for early rebleeding of diverticular bleeding were evaluated. RESULTS Clinical behavior: Bleeding diverticula were identified in 23 of 124 (19%) patients and most of them (16/23; 70%) were located in the ascending colon. Hemostasis was achieved in all 23 cases, however, six (26%) developed early rebleeding. Factors for detecting bleeding diverticula: In patients in whom extravasation was detected using CECT, the endoscopic detection rate of bleeding diverticula was 60% (12/20), while bleeding diverticula were detected in only 31% (11/35) of patients in whom extravasation was not detected using CECT (p<0.05). The interval between the first hematochezia and colonoscopy in which the bleeding point was detected by colonoscopy (median 23.5 hours) was shorter than that in which bleeding diverticula were not detected (median 43.6 hours) (p<0.01). Risk factors for short term rebleeding: Using a univariate analysis, atherosclerotic comorbidity, anti-inflammatory drugs including low-dose aspirin, antithrombotic agents, vital signs on admission, hemoglobin level on hospitalization, and extravasation on CECT were not found to be significant risk factors. CONCLUSION The finding of extravasation on CECT is the most important factor for identifying and treating bleeding diverticula by colonoscopy. In such cases, urgent colonoscopy is recommended.

Clinical factors related to long-term administration of sorafenib in patients with hepatocellular carcinoma.

Background Sorafenib has been approved in the indication of unresectable hepatocellular carcinoma, but there are many cases in which administration of the drug is discontinued due to severe side effects. In this study, we compared the characteristics of patients who continued and discontinued sorafenib. Methods Ninety-six patients (75 men and 21 women) were initiated on sorafenib from July 2009 through September 2011. The patient characteristics of interest included gender, age, etiology, Child-Pugh classification, treatment history and frequency, and levels of α-fetoprotein, des- gamma-carboxy prothrombin, aspartate amino acid transferase, and alanine aminotransferase. Duration of administration of sorafenib and reasons for its discontinuation were compared. Results Median overall survival was 11.8 months. Discontinuation of sorafenib within 90 days was identified as an independent prognostic factor for overall survival on multivariate analysis (P < 0.0001). Transarterial chemoembolization performed six times or more (P = 0.013) was also identified as an independent factor contributing to discontinuation of sorafenib within 90 days in multivariate analysis. Patients who received sorafenib for ≥90 days had significantly longer overall survival than those who discontinued it (P < 0.0001). Conclusion Prolonged treatment with sorafenib is an important factor in achieving extended overall survival. We recommend starting sorafenib before latent liver damage has occurred as a result of too many transarterial chemoembolization procedures.

Helicobacter pylori eradication decreases the expression of glycosylphosphatidylinositol-anchored complement regulators, decay-accelerating factor and homologous restriction factor 20, in human gastric epithelium.

Background: It has previously been reported that there is a strong correlation between the expression of glycosylphosphatidylinositol (GPI)‐anchored complement membrane inhibitor in gastric epithelium and the severity of inflammation of gastric mucosa. To investigate the regulation of complement activity in gastric epithelium during Helicobacter pylori (H. pylori)‐associated gastritis, the expression of GPI‐anchored complement membrane inhibitors, decay‐accelerating factor (DAF) and 20‐kDa homologous restriction factor 20 (HRF20), and membrane cofactor protein (MCP), which is a transmembrane protein, were evaluated after removal of the H. pylori stimulus. Furthermore, the expression of the complement fragment, C3c, was also investigated.

Hepatitis G virus infection in patients with alcoholic liver disease

The recently discovered hepatitis G virus (HGV) is believed to be a single-stranded RNA virus belonging to the Flaviviridae family, similar to hepatitis C virus (HCV), but much remains to be learned about its characteristics and clinical manifestations. Although it has been suggested that alcohol intake might have an effect on liver pathology by promoting the proliferation of HCV, the association between HGV infection and alcohol intake is yet to be elucidated. In the present study, we investigated the prevalence of HGV-RNA and HCV-RNA in 63 patients with alcoholic liver disease, and studied the effects of alcohol on the progression of hepatic damage in HGV-RNA positive patients. Among these 63 patients, 9 (14%) were HGV-RNA-positive and 37 (59%) were HCV-RNA-positive. Seven (78%) of the nine HGV-RNA positive patients were also infected with HCV. The patients showed no significant differences of clinical features in relation to the presence or absence of HGV infection. There were also no differences of liver histology among HCV-RNA-positive patients with or without HGV-RNA. The two patients infected with HGV alone had alcoholic hepatitis and nonspecific reactive hepatitis, respectively. In this study, alcohol seemed to have little influence on the progression of the liver histology in HGV-RNA-positive patients.

The Successful Treatment of Sodium Polystyrene Sulfonate-induced Enteritis Diagnosed by Small Bowel Endoscopy

Sodium polystyrene sulfonate (SPS: KayexalateⓇ) is an ion-exchange resin used to treat hyperkalemia in patients with chronic kidney disease. It is known that this resin sometimes causes colonic necrosis and perforation, but there are few reports about small bowel necrosis associated with SPS. We herein report the case of a patient who developed SPS-induced small bowel necrosis, which was diagnosed based on the examination of a small bowel endoscopic biopsy specimen. The SPS-induced small bowel necrosis was resistant to conservative treatment including the cessation of SPS, and finally required surgical bowel resection.

Long-term Outcomes of One Stage Surgery Using Transanal Colorectal Tube for Acute Colorectal Obstruction of Stage II/III Distal Colon Cancer

Purpose Since oncological outcomes of transanal colorectal tube (TCT) placement, an endoscopic treatment for colorectal cancer (CRC) with acute colorectal obstruction (ACO), remain unknown, this study analyzed long-term outcomes of TCT placement for stage II/III CRC with ACO. Materials and Methods Data were retrospectively reviewed from consecutive patients with distal stage II/III CRC who underwent surgery between January 2007 and December 2011 at two Japanese hospitals. One hospital conducted emergency surgery and the other performed TCT placement as the standard treatment for all CRCs with ACO. Propensity score (PS) matching was used to adjust baseline characteristics between two groups. Results Among 754 patients with distal stage II/III CRC, 680 did not have ACO (non-ACO group) and 74 had ACO (ACO group). The PS matching between both hospitals identified 234 pairs in the non-ACO group and 23 pairs in the ACO group. In the non-ACO group, the surgical quality was equivalent between the two institutions, with no significant differences in overall survival (OS) and disease-free survival (DFS). In the ACO group, the rate of primary resection/anastomosis was higher in the TCT group than in the surgery group (87.0% vs. 26.1%, p < 0.001). No significant differences were noted between the surgery and the TCT groups in OS (5-year OS, 61.9% vs. 51.5%; p=0.490) and DFS (5-year DFS, 45.9% vs. 38.3%; p=0.658). Conclusion TCT placement can achieve similar long-term outcomes to emergency surgery, with a high rate of primary resection/anastomosis for distal stage II/III colon cancer with ACO.