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Background and aim: Complement receptor type 1 (CR1] is a transmembrane protein, and human erythrocyte CR1 (E-CR1) is involved in the transport of circulating immune complexes (IC] from the circulation [...]

Objective Although Barrett's adenocarcinoma (BA) remains a minor disease in Japan, its incidence has been gradually increasing. We analyzed the characteristics of BA in Japanese populations. Methods We retrospectively reviewed medical records and analyzed the clinicopathological differences between short-segment Barrett's esophagus (SSBE) and long-segment Barrett's esophagus (LSBE), as well as metastasis. Local recurrence and metachronous lesions were analyzed only in patients who underwent endoscopic resection (ER). Patients Consecutive patients who had pathological T1 BAs resected by ER or surgery from January 2003 to December 2017. Results A total of 168 patients were analyzed, including 139 with SSBE and 29 with LSBE. In total, 67% of the SSBE lesions and 32% of the LSBE lesions were located between 0 and 3 o'clock (p=0.0014). No patients who achieved pathological margin-free resection (pR0) and 17% of patients who did not achieve pR0 experienced local recurrence (p=0.0131). None of the patients without lymphovascular involvement, a poorly differentiated component, lesion size of >30 mm, and submucosal invasion of >500 μm experienced metastasis. The 5-year cumulative incidence rate of metachronous BA after ER was 0% in patients with SSBE and 40% in patients with LSBE (p=0.0005). Conclusion Superficial BA was likely to be detected at the right anterior wall of SSBE in the Japanese population. The risk for metachronous BA after ER was high in Japanese patients with LSBE, as in Western patients.

Background and Aim: Although oral mesalamine is the first-choice drug for treating mild-to-moderate ulcerative colitis (UC), some patients show symptoms of intolerance, including exacerbation of diarrhea and abdominal pain. The present study clarified the current state and clinical courses of patients with mesalamine intolerance., Methods: Patients who were diagnosed with UC and administered oral mesalamine at eight hospitals in Japan with a follow-up period exceeding 1 year were analyzed., Results: Sixty-seven (11%) of 633 patients showed intolerance to at least one formulation of oral mesalamine. The frequency of mesalamine intolerance has increased in recent years, rising from 5.3% in 2007-2010 to 9.1% in 2011-2013 and 16.2% in 2014-2016. The most common complications were the exacerbation of diarrhea (n = 29), a fever (n = 25), and abdominal pain (n = 22). Readministration of mesalamine/sulfasalazine was attempted in 43 patients, mostly with other types of formulation of mesalamine, and more than half of these patients proved to be tolerant. The risk factors for mesalamine intolerance were female gender (odds ratio [OR] = 1.83; 95% confidence interval [CI], 1.08-3.12), age < 60 years old (OR = 2.82; CI, 1.19-8.33), and pancolitis (OR = 2.09; 95% CI, 1.23-3.60). There were no significant differences in the use of anti-tumor necrosis factor-α agents, colectomy, or steroid-free remission at the last visit between patients with and without mesalamine intolerance., Conclusions: Mesalamine intolerance is not rare, and its frequency has been increasing recently. The prognosis of patients with mesalamine intolerance did not differ significantly from that of those without intolerance., (© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Objective Gastric endoscopic submucosal dissection (ESD) under heparin replacement (HR) of warfarin reportedly has a high risk of delayed bleeding (24-57%). It is possible that the delayed bleeding risk may have changed over the years. We evaluated the current risk of delayed bleeding after gastric ESD under HR of anticoagulant agents. Methods We retrospectively reviewed the delayed bleeding rate and analyzed the risk factors for delayed bleeding. Patients Consecutive patients who underwent gastric ESD under HR of anticoagulant agents from July 2015 to June 2017. Results A total of 32 patients with a solitary early gastric cancer and taking anticoagulant agents were analyzed, including 24 patients on warfarin (the warfarin group) and 8 patients on direct oral anticoagulants (the DOAC group). Three (9.4%) patients experienced delayed bleeding: three (12.5%) patients in the warfarin group and no patients in the DOAC group. Continued aspirin treatment was identified to be a risk factor of delayed bleeding (p=0.01). Conclusion Careful management may be required for patients undergoing gastric ESD under continued aspirin treatment in addition to HR of anticoagulant agents; although the delayed bleeding risk after gastric ESD under HR of anticoagulant agents might have decreased over the years.

Background and Aim: Bleeding is an inevitable and often severe complication after endoscopic sphincterotomy (EST). We aimed to investigate the factors associated with post-EST bleeding in patients treated with anticoagulants., Methods: The data of patients who underwent EST at 15 hospitals between July 2015 and June 2017 were extracted. We investigated the incidence of post-EST bleeding and risk factors for bleeding in patients treated with anticoagulants., Results: One hundred forty-nine patients undergoing EST who met the inclusion criteria were included in this study. The total-EST bleeding (bleeding occurring during or after EST) rate did not differ between the heparin replacement (8.0%, 6/75) and continuation (16.6%, 2/12; P = 0.37) groups of warfarin users. The total-EST-bleeding rate in the heparin replacement group (12.9%, 4/31) was significantly higher than that in the continuation group (0%, 0/31; P = 0.016) in direct oral anticoagulant (DOAC) users. The rate of total-EST bleeding with continuation of DOAC (0%, 0/31) was significantly lower with continuation of warfarin (16.6%, 2/12; P = 0.021). During-EST bleeding (bleeding occurring during EST) (P = 0.0083) and precut (P = 0.033) were significant risk factors for post-EST bleeding in all 149 patients. Heparin replacement was only a significant risk factor for total-EST bleeding (P = 0.033) in DOAC users., Conclusion: Heparin replacement was a significant risk factor for post-EST bleeding in DOAC users; however, there was no significant difference between the bleeding rate of heparin replacement and that of continuation groups in patients taking warfarin. During EST and precut were significant risk factors for post-EST bleeding in all patients treated with anticoagulants., (© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aim: Although previous studies compared the efficacy of infliximab (IFX) versus adalimumab (ADA) as the first-line biologics for Crohn's disease (CD), the difference in long-term prognosis based on which biologic was used first has scarcely been reported. In particular, the clinical courses after loss of response (LOR) of the first-line biologics are largely unknown., Methods: A multicenter, retrospective study was performed. Disease courses of biologic-naïve CD patients who were started on IFX or ADA treatment were evaluated, even after LOR of the initial biologics., Results: In total, 263 CD patients were eligible for analysis, 183 were treated with IFX first, and 80 were treated with ADA first. The median observation period was 64.2 months. The cumulative steroid-free remission rates and surgery-free rates did not differ significantly between the patients treated with IFX first and those treated with ADA first (log-rank test P = 0.42 and P = 0.74, respectively). In addition, no significant difference was observed in the rate of occurrence of events associated with ineffectiveness (modification of anti-tumor necrosis factor treatment including intensification, switch, discontinuation, or surgery) between the patient groups (log-rank test P = 0.62). The patients treated with IFX first were likely to discontinue the agent due to adverse events, whereas those treated with ADA first were likely to discontinue due to treatment failure or LOR., Conclusions: No significant difference was observed in the long-term prognosis between biologic-naïve patients with CD who were started treatment with IFX first and ADA first., (© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Aim: In 1990, an epidemiological survey by ship in some Japanese islands revealed high prevalence of hepatitis viruses and human T cell leukemia virus (HTLV). A second prevalence study of these viruses were accomplished in 2018, 28 years after initial survey. Analysis of these studies provide insights about strategies of elimination of hepatitis viruses at remote areas., Materials and Methods: In 2018, prevalence of hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), and HTLV was checked in 305 subjects in the islands those covered in 1990's survey. Hepatitis A virus was checked by the presence of anti-HAV IgG in sera; HBV was affirmed when hepatitis B surface antigen (HBsAg) in sera. Hepatitis C virus infection was evaluated by the presence of antibody to HCV (anti-HCV) and infection with HTLV was estimated by immunoassay. The methodology of assessment of different hepatitis viruses were optimized on the basis of present scientific knowhow., Results: In 1990, the prevalence of HAV (presence of anti-HAV), HBV (presence of HBsAg), HCV (positivity for anti-HCV), and HTLV was found in 79.3%, 11.1%, 2.2%, and 3.3% of apparently health subjects of the islands, respectively. The prevalence of HAV, HBV, HCV, and HTLV was 47.9%, 4.6%, 1.0%, and 3.0%, respectively, in 2018. A shift of age of infected persons tilted towards right as the days progressed., Conclusion: The study indicates a scenario of elimination of hepatitis viruses in Japan as lower trends of prevalence of HAV, HBV, and HCV have been recorded in 2018 compared with 1990, mainly by preventive measures. The most notable finding is that there are almost no new case below the age of 40 years, indicating an effective containment measure against these viruses., How to Cite This Article: Akao T, Onji M, Kawasaki K, et al . Surveillance of Hepatitis Viruses in Several Small Islands of Japan by Ship: A Public Health Approach for Elimination of Hepatitis Viruses by 2030. Euroasian J Hepato-Gastroenterol 2019;9(2):57-62., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2019; Jaypee Brothers Medical Publishers (P) Ltd.)

Aim: The aim of the study was to assess the implication of Zonulin, a mediator protein synthesized by intestine and the liver,in patients with chronic liver diseases., Materials and Methods: Twenty-six patients with chronic liver diseases due to hepatitis C virus (HCV) and hepatitis B virus (HBV) were enrolled in this study. Out of total 26 patients, 17 were diagnosed as chronic hepatitis (CH) and 9 were patients with liver cirrhosis (LC). Twenty-four of these patients were infected with hepatitis C virus (HCV) and the rest two by hepatitis B virus (HBV). The study was conducted at Saiseikai-Imabari Hospital, Imabari, Ehime, Japan. Serum levels of Zonulin along with different parameters of liver function test were measured in all patients and comparative analyses were accomplished., Results: The serum levels of Zonulin were significantly lower in CH patients compared to controls (p<0.001). Also, the levels of Zonulin were significantly lower in patients with LC compared to CH and normal controls (p<0.001). Further analysis revealed that serum Zonulin was significantly lower in patients with LC having ascites than those without ascites (p <0.05). There was a significant correlation of serum levels of Zonulin with platelet count, cholinesterase, and albumin in patients with chronic liver diseases., Discussion: Decreased levels of Zonulin may be related to impaired production of this mediator in the diseased liver. It will be tempting to assess the regulation of Zonulin in the liver, a production site of the mediator., Abbreviations: LC: Liver cirrhosis, CH: Chronic hepatitis, HCV: Hepatitis C virus, HBV: Hepatitis B virus, LGS: Leaky gut syndrome How to cite this article: Akao T, Morita A, Onji M, Miyake T, Watanabe R, Uehara T, Kawasaki K, Miyaike J, Oomoto M. Low Serum Levels of Zonulin in Patients with HCV-Infected Chronic Liver Diseases. Euroasian J Hepatogastroenterol, 2018;8(2):112-115., Competing Interests: Source of support: Nil Conflict of interest: None

A 76-year-old male had a solitary submucosal tumor-like lesion in the sigmoid colon originating from tuberculosis. The lesion, up to 1 cm in diameter, was found incidentally during a routine colonoscopy, which revealed a protuberant submucosal growth with a shallow depression of the overlying mucosa in the center of the tumor. Histologically, the endoscopic biopsy revealed caseating granulomas and infiltration of Langhans giant cells and epithelioid cells, consistent with tuberculosis, were also observed. Five reports of similar lesions from colon tuberculosis were found in a literature review, including the present case. In all cases, the submucosal tumor-like lesions which originated from tuberculosis were small and in an active stage of tuberculosis. Five cases of submucosal tumor-like lesions from gastric tuberculosis were also reported, with characteristics very similar to those of the lesions from colon tuberculosis. Therefore, we propose that lesions originating from tuberculosis should be included in the differential diagnosis of submucosal tumor-like lesions in the colon and stomach.

Background: Although the outcomes of pancreatic cancer have been improved by gemcitabine, the changes in its characteristics and long-term outcomes within the gemcitabine era remain unclear. This study was conducted to identify clinical characteristics of pancreatic cancer patients within the gemcitabine era., Methods: A retrospective chart review was performed at 10 centers for 1,248 consecutive patients who were ever considered to have a diagnosis of pancreatic cancer between 2001 and 2010. Data collected included demographics, diagnosis date, clinical stage, treatment, and outcome 1,082 patients met the inclusion criteria and were analyzed further. The chi-square test, Student's t-test, and Mann-Whitney U-test were used for statistical analysis. Outcomes were analyzed using the Kaplan-Meier method and Cox proportional hazards regression. Differences in survival analyses were determined using the log-rank test., Results: The distribution of clinical stages was: I, 2.2% II, 3.4% III, 13% IVa, 27% and IVb, 55%. Chemotherapy alone was administered to 42% of patients and 17% underwent resection. The 1-, 3-, and 5-year survival rates were 39%, 13%, and 6.9%, respectively. The median survival time was 257 days, but differed considerably among treatments and clinical stages. Demographics, distribution of clinical stage, and cause of death did not differ between groups A (2001-2005, n=406) and B (2006-2010, n=676). However, group B included more patients who underwent chemotherapy (P<0.0001) and fewer treated with best supportive care (P=0.0004), mirroring improvements in this group's long-term outcomes (P=0.0063). Finally, factors associated with long-term outcomes derived from multivariate analysis were clinical stage (P<0.0001), location of the tumor (P=0.0294) and treatments (surgery, chemotherapy) (<0.0001)., Conclusions: Long-term outcomes in pancreatic cancer has improved even within the gemcitabine era, suggesting the importance of offering chemotherapy to patients previously only considered for best supportive care. Most patients are still diagnosed at an advanced stage, making clinical strategy development for diagnosing pancreatic cancer at earlier stages essential.

Background: A few reports suggest that the emergence of double balloon endoscopy (DBE) has likely changed the clinical picture of small bowel tumors (SBTs)., Aim: To further clarify the characteristics of SBTs detected by DBE., Methods: A retrospective chart review was conducted in 227 patients who had undergone DBE., Results: The SBT group contained more symptomatic patients than the non-SBT group (90% vs. 49%, P<0.0005) with a significantly higher rate of gastrointestinal symptoms at presentation (72% vs. 33%, P<0.005). Twenty patients (8.8%) were eventually diagnosed with SBT, and their indications for DBE were obscure gastrointestinal bleeding (n=5), abdominal pain (n=5), abdominal fullness (n=5), vomiting (n=2), and diarrhea (n=1). Tumors were located in the jejunum in 14 patients (70%) and in the ileum in 6 (30%). A final histological diagnosis was assigned to all 20 patients: primary adenocarcinoma (n=8, 40%), malignant lymphoma (n=5, 25%), metastatic cancer (n=4, 20%), gastrointestinal stromal tumor (n=1, 5%), carcinoid tumor (n=1, 5%) and inflammatory fibroid polyp (n=1, 5%). Stenosis or ulceration were the most frequently observed endoscopic findings (n=13, 65%). All primary adenocarcinomas and three of four (75%) metastatic cancers showed stenosis or ulceration. Three of five (60%) malignant lymphomas showed multiple lymphomatous polyps. All patients but one underwent surgical resection or chemotherapy or both., Conclusion: DBE is a safe and useful procedure that enables a precise diagnosis of SBTs.

Background/aims: Although enteral nutrition therapy has been highlighted as maintenance therapy for Crohn's disease, few reports have investigated the impact of enteral nutrition on the health-related quality of life of Crohn's disease patients., Methodology: We cross-sectionally evaluated the effect of multiple clinical factors including enteral nutrition on the health-related quality of life of Crohn's disease patients focusing on patient disease duration using the Inflammatory Bowel Disease Questionnaire., Results: Of all 126 patients examined, 95 patients were receiving enteral nutrition. Multiple linear regression analysis using 18 clinical parameters revealed that disease activity was a dominant factor that affected the health-related quality of life of Crohn's disease patients, and that enteral nutrition was also an independent factor that improved the Inflammatory Bowel Disease Questionnaire total score, bowel symptoms, and systemic symptoms for patients with a disease duration of 10 years or more (P = 0.0090, 0.0033, and 0.016, respectively)., Conclusions: Enteral nutrition improved the health-related quality of life of Crohn's disease patients with long-term disease duration. Thus, enteral nutrition should be recommended as one of the options for maintenance therapy for Crohn's disease.

Background/aims: Despite appropriate medical treatment, a large part of CD patients undergo surgery. In this study, we aimed to identify the risk factors and indications for first surgery in CD patients., Methodology: The clinical records of 289 consecutive Japanese CD patients treated at 23 hospitals between January 1981 and August 2003 were reviewed. Clinical factors, including gender, age at onset, year at onset, and disease extent were examined, in order to identify the risk factors for first surgery. In addition, indications for first surgery were investigated, and stratified by these risk factors., Results: A total of 113 (39%) patients underwent surgery at least once. Female gender (RR, 1.62; 95% CI, 1.09-2.41), and disease affecting the ileum (RR, 2.06; 95% CI, 1.20-3.53) were identified as the independent risk factors for surgery. In addition, female CD patients were more likely to undergo first surgery due to the indication of perforation than male patients (25% vs. 6%, p=0.006). Recent clinical and demographic changes of Japanese CD patients, such as increases in female and aged patients, did not affect the surgical risk factors and indications., Conclusions: Female CD patients should be consulted with special attention to the high risk of surgery due to perforation.

Purpose: Despite progress in medical treatment for ulcerative colitis, a considerable fraction of ulcerative colitis patients undergo colectomy. We analyzed the clinical variables of ulcerative colitis patients and determined the risk factors and indications for colectomy., Methods: The clinical records of 981 consecutive Japanese patients with ulcerative colitis were reviewed both retrospectively and prospectively., Results: Of 981 patients with ulcerative colitis, 85 patients underwent colectomy. Multivariate analysis indicated that male gender (risk ratio, 2.16; 95 percent confidence interval, 1.37-3.42), onset year during and after 2000 (risk ratio, 2.85; 95 percent confidence interval, 1.31-6.22), severe disease activity (risk ratio, 2; 95 percent confidence interval, 1.15-3.48), corticosteroid resistance (risk ratio, 7.05; 95 percent confidence interval, 4.29-11.59), and complications because of corticosteroid administration (risk ratio, 3.55; 95 percent confidence interval, 2.08-6.06) were significant risk factors for colectomy. In patients with disease duration of more than five years, only corticosteroid resistance and complications because of corticosteroid were significant risk factors for colectomy. When we stratified indications for colectomy for the 85 cases via patient disease duration, massive hemorrhage was a relatively frequent cause of colectomy in patients with a disease duration of less than five years (P = 0.091). On the other hand, colon dysplasia or cancer was a major cause for colectomy in patients with a disease duration of more than ten years (P = 0.0001)., Conclusions: In ulcerative colitis patients, the risk factors and indications for colectomy were different according to the patient's clinical background. Our findings may help to predict patients with ulcerative colitis who have a high risk for colectomy.

The aim of this work was to determine whether intratumour contents of thymidine phosphorylase (TP), which converts 5'-deoxy-5-fluorouridine (5'-DFUR) to 5-fluorouracil, and dihydropyrimidine dehydrogenase (DPD), which degrades 5-fluorouracil to inactive molecules, could be useful in predicting the response of patients with metastatic gastric cancer to chemotherapy using 5'-DFUR. Endoscopic biopsy specimens for the measurement of TP and DPD were obtained from the primary lesions before the start of combination chemotherapy, in which 5'-DFUR, cisplatin and mitomycin C were administered. TP and DPD were measured by enzyme-linked immunosorbent assays after the objective responses to chemotherapy had been confirmed. Twenty five patients were enrolled in this study and data for 22 patients in whom responses were confirmed were analysed. The median levels (ranges) of TP and DPD were 80 (4.9-360) and 44 (15-82) U/mg protein, respectively. The median value (range) of TP to DPD ratios was 1.9 (0.25-5.1). Eight patients with a complete or partial response to chemotherapy had significantly higher TP to DPD ratios than did the remaining patients with stable or progressive disease (P = 0.014). When a cut-off level of TP to DPD ratio was defined as the median value, the high-ratio group (n = 11) showed a significantly higher response rate (64% vs. 9.1%, P = 0.024) than the low-ratio group (n = 11). Overall survival of the high-ratio group was significantly longer than that of the low-ratio group (the median survival time; 300 days vs. 183 days, P = 0.047). The efficacy of 5'-DFUR could be optimised by preselecting patients with high TP/ DPD ratios in their tumour tissues, and this would be applicable to the treatment with capecitabine.

Background: 2',5'-Oligoadenylate synthetases (2-5AS) are type I interferon (IFN)-induced proteins with antiviral capacity. Three major forms of 2-5AS with distinct enzymatic activities have been described in IFN-treated human cells. We measured distinct forms of 2-5AS mRNA to analyze the relationship with its enzymatic activity and response to IFN therapy in chronic hepatitis C., Methods: We established a method to quantify p40/p46 and p69/p71 forms of 2-5AS mRNA by use of reverse transcription followed by competitive PCR. The 2-5AS mRNA concentrations were measured in peripheral blood mononuclear cells from 40 patients with chronic hepatitis C and 28 control individuals., Results: Reconstitution experiments and comparison with Northern blot analyses revealed that our method accurately and linearly quantified 2-5AS mRNA. 2-5AS mRNA concentrations and 2-5AS enzymatic activity were correlated (P <0.03). Our data demonstrated a correlation in 2-5AS mRNA between p40/p46 and p69/p71 (P <0.02), indicating a similar regulation of the expression of these genes. Our data also demonstrated that pretreatment concentrations of 2-5AS mRNA correlated with responses to IFN therapy in chronic hepatitis C., Conclusions: Our method for measuring 2-5AS mRNA concentrations could provide an important marker for selecting patients for IFN therapy and may be useful for the development of more effective therapeutic strategies for chronic hepatitis C.

It has been documented that the serum complement activities measured by hemolytic assay (CH50) are decreased after storage of sera at a low temperature in some patients with chronic hepatitis C. However, the mechanism of this phenomenon has not been identified yet. Here, we tried to elucidate factors involved in the cold activation of complement (CAC). To clarify what pathway is activated in CAC, we measured complement cleavage products after cold storage of sera. C4d increased significantly after 12 h-storage at cold temperatures in 5 CAC (+) sera compared with 5 CAC (-) (P < 0.01) and 3 control sera (P < 0.05), while Bb did not increase in any of the groups. In order to determine whether IgG or IgG complex is necessary for CAC, 8 CAC (+) sera were incubated with Protein G Sepharose gel beads, and all of them retained hemolytic activities to some extent after cold storage. Column chromatography through Superose 6HR of CAC-positive serum identified the fractions containing molecules that induced CAC in normal serum, which were depleted by treatment with protein G Sepharose. In conclusion, CAC in hepatitis C seems to occur via a classical or lectin pathway, and the IgG complex produced in hepatitis C virus infection may be an important factor in inducing CAC, a common extrahepatic manifestation of hepatitis C.