Masatake Kuroha

Impact of a transparent hood on the performance of total colonoscopy : a randomized controlled trial

BACKGROUND Clinical demand for total colonoscopy (TCS) is increasing. Improvement of the cecal intubation rate and shortening of the examination time would expand the capacity for TCS. OBJECTIVE To assess the efficacy of a transparent hood attached to the tip of a colonoscope for cecal intubation in TCS. DESIGN Prospective, randomized, controlled study. SETTING Single tertiary-referral center. INTERVENTIONS TCS. MAIN OUTCOME MEASUREMENTS Cecal intubation time and rate, complications, patient discomfort, and detection rate of colonic polyps. METHODS Patients who were to undergo screening and/or surveillance TCS for colorectal cancer were invited to participate in the study. Cecal intubation time and rate, complications, patient discomfort, and detection rate of colonic polyps were evaluated. RESULTS A total of 592 patients enrolled in this study were randomly allocated to the hood group and no-hood group. The mean (SD) cecal intubation time in the hood group and the no-hood group was 10.2 +/- 12.5 minutes and 13.4 +/- 15.8 minutes, respectively (P = .0241). The effect of its use was more prominent in the expert endoscopists group compared with those with moderate experience. The cecal intubation rate and the detection rate of small polyps in the 2 groups were similar. The grade of patient discomfort was significantly lower in the hood group. No complications were encountered with the use of the hood. CONCLUSIONS Use of a transparent hood on the tip of a colonoscope shortened the time required for cecal intubation and decreased patient discomfort; such use was more effective among experts in shortening the examination time.

Erratum to: FCGR3A-158 polymorphism influences the biological response to infliximab in Crohn’s disease through affecting the ADCC activity

An association between FCGR3A-158 V/F polymorphism and biological responses to infliximab has been reported in Crohn’s disease (CD) in Western countries. However, little is known about the mechanism by which gene polymorphism affects the responses to infliximab. The aims of this study were to confirm the association in Japanese CD patients and to reveal the effect of gene polymorphism on biological responses to infliximab. Japanese CD patients were examined retrospectively at weeks 8 and 30. Clinical and biological responses were assessed by the Crohn’s disease activity index and C-reactive protein levels, respectively. The infliximab-binding affinity of natural killer (NK) cells from FCGR3A-158 V/V, V/F and F/F donors was examined. Infliximab-mediated antibody-dependent cell-mediated cytotoxicity (ADCC) activities were also determined using transmembrane TNF-α-expressing Jurkat T cells as target cells and peripheral blood mononuclear cells (PBMCs) from V/V, V/F and F/F donors as effector cells. Biological responses at week 8 were statistically higher in V/V patients, whereas no significant differences were observed in either clinical responses at weeks 8 and 30 or biological responses at week 30 among the three genotypes. NK cells and PBMCs from V/V patients also showed higher infliximab-binding affinity and infliximab-mediated ADCC activity, respectively. Our results suggest that FCGR3A-158 polymorphism is a predicting factor of biological responses to infliximab in the early phases. FCGR3A-158 polymorphism was also found to affect the infliximab-binding affinity of NK cells and infliximab-mediated ADCC activity in vitro, suggesting that an effect on ADCC activity influences biological responses to infliximab in CD patients.

Modulation of endoplasmic reticulum (ER) stress-induced autophagy by C/EBP homologous protein (CHOP) and inositol-requiring enzyme 1α (IRE1α) in human colon cancer cells.

To explore the relationship between UPR and autophagy in intestinal epithelial cells, we investigated whether autophagy was induced by endoplasmic reticulum (ER) stress in colon cancer cell lines. We demonstrated that autophagy was induced by ER stress in HT29, SW480, and Caco-2 cells. In these cells, inositol-requiring enzyme1α (IRE1α) and C/EBP homologous protein (CHOP) were involved in the ER stress-autophagy pathway, and CHOP was a regulator of IRE1α protein expression. Our findings suggest that CHOP promotes IRE1α and autophagy especially in ER stress conditions. This study will provide important insights into the disclosure of the ER stress-autophagy pathway.

Life-event stress induced by the Great East Japan Earthquake was associated with relapse in ulcerative colitis but not Crohn's disease: a retrospective cohort study

Objective Stress is thought to be one of the triggers of relapses in patients with inflammatory bowel disease (IBD). We examined the rate of relapse in IBD patients before and after the Great East Japan Earthquake. Design A retrospective cohort study. Settings 13 hospitals in Japan. Participants 546 ulcerative colitis (UC) and 357 Crohns disease (CD) patients who received outpatient and inpatient care at 13 hospitals located in the area that were seriously damaged by the earthquake. Data on patients clinical characteristics, disease activity and deleterious effects of the earthquake were obtained from questionnaires and hospital records. Primary outcome We evaluated the relapse rate (from inactive to active) across two consecutive months before and two consecutive months after the earthquake. In this study, we defined ‘active’ as conditions with a partial Mayo score=2 or more (UC) or a Harvey-Bradshaw index=6 or more (CD). Results Among the UC patients, disease was active in 167 patients and inactive in 379 patients before the earthquake. After the earthquake, the activity scores increased significantly (p<0.0001). A total of 86 patients relapsed (relapse rate=15.8%). The relapse rate was about twice that of the corresponding period in the previous year. Among the CD patients, 86 patients had active disease and 271 had inactive disease before the earthquake. After the earthquake, the activity indices changed little. A total of 25 patients experienced a relapse (relapse rate=7%). The relapse rate did not differ from that of the corresponding period in the previous year. Multivariate analyses revealed that UC, changes in dietary oral intake and anxiety about family finances were associated with the relapse. Conclusions Life-event stress induced by the Great East Japan Earthquake was associated with relapse in UC but not CD.

MicroRNA-320 family is downregulated in colorectal adenoma and affects tumor proliferation by targeting CDK6.

AIM To investigate the microRNA (miRNA) expression during histological progression from colorectal normal mucosa through adenoma to carcinoma within a lesion. METHODS Using microarray, the sequential changes in miRNA expression profiles were compared in colonic lesions from matched samples; histologically, non-neoplastic mucosa, adenoma, and submucosal invasive carcinoma were microdissected from a tissue sample. Cell proliferation assay was performed to observe the effect of miRNA, and its target genes were predicted using bioinformatics approaches and the expression profile of SW480 transfected with the miRNA mimics. mRNA and protein levels of the target gene in colon cancer cell lines with a mimic control or miRNA mimics were measured using qRT-PCR and Western blotting. The expression levels of miRNA and target gene in colorectal tissue samples were also measured. RESULTS Microarray analysis identified that the miR-320 family, including miR-320a, miR-320b, miR-320c, miR-320d and miR-320e, were differentially expressed in adenoma and submucosal invasive carcinoma. The miR-320 family, which inhibits cell proliferation, is frequently downregulated in colorectal adenoma and submucosal invasive carcinoma tissues. Seven genes including CDK6 were identified to be common in the results of gene expression array and bioinformatics analyses performed to find the target gene of the miR-320 family. We confirmed that mRNA and protein levels of CDK6 were significantly suppressed in colon cancer cell lines with miR-320 family mimics. CDK6 expression was found to increase from non-neoplastic mucosa through adenoma to submucosal invasive carcinoma tissues and showed an inverse correlation with miR-320 family expression. CONCLUSION MiR-320 family affects colorectal tumor proliferation by targeting CDK6, plays important role in its growth, and is considered to be a biomarker for its early detection.

A Comparison of Short- and Long-Term Therapeutic Outcomes of Infliximab- versus Tacrolimus-Based Strategies for Steroid-Refractory Ulcerative Colitis

Background/Aims. Antitumor necrosis factor antibodies and calcineurin inhibitors have shown good therapeutic efficacy for steroid-refractory ulcerative colitis (UC). Although some studies have compared the efficacy of infliximab (IFX) and cyclosporin A, there are no published studies comparing IFX and tacrolimus (Tac). This study aimed to compare therapeutic efficacies between IFX- and Tac-based strategies for steroid-refractory UC. Methods. Between July 2009 and August 2013, 95 patients with steroid-refractory UC received either IFX (n = 48) or Tac (n = 47) in our hospital. In the IFX group, the patients continued to receive maintenance treatment with IFX. In the Tac group, patients discontinued Tac treatment up to 3 months and subsequently received thiopurine. We retrospectively compared the therapeutic outcomes between the groups. Results. There was no significant difference in the colectomy-free rate, clinical remission rate, and clinical response rate at 2 months between the groups. However, relapse-free survival was significantly higher in the IFX group than in the Tac group (p < 0.001; log-rank test). The proportions of serious adverse events did not differ between the groups. Conclusion. The findings of our study showed that IFX and Tac have similar short-term therapeutic efficacy for steroid-refractory UC. Maintenance treatment with IFX, however, yields better long-term outcomes than Tac-thiopurine bridging treatment.

Long-tube insertion with the ropeway method facilitated by a guidewire placed by transnasal ultrathin endoscopy for bowel obstruction: a prospective, randomized, controlled trial

BACKGROUND It is often difficult to insert a long intestinal tube in the small bowel of patients with bowel obstruction, and it often results in long procedure time and severe patient distress. OBJECTIVE To assess the usefulness of the ropeway method by using a guidewire placed with the assistance of transnasal ultrathin endoscopy in long-tube insertion for patients with bowel obstruction. DESIGN Prospective, randomized, controlled, single-center study. PATIENTS AND INTERVENTIONS Thirty-four consecutive patients with bowel obstruction requiring decompression participated in the study and were randomized to the insertion of a long tube with the ropeway method (ILTR) group (ie, insertion along an endoscopically placed guidewire that was passed through only the distal 4 cm of the tube) or insertion by a conventional method group (C group). MAIN OUTCOME MEASUREMENTS The time required for the procedure (main), success rate, x-ray exposure time, and intensity of patient distress measured with a visual analog scale of 1 to 5 (better to worse). RESULTS The mean (+/- standard deviation) duration of the procedure in the successful cases in the ILTR group and the C group was 16.1 +/- 5.6 minutes and 26.4 +/- 13.8 minutes, respectively (P = .010). The success rate was 100% in the ILTR group and 88% in the C group (P = .48). The mean (+/- standard deviation) x-ray exposure time and intensity of patient distress were, respectively, 16.4 +/- 8.7 minutes and 33.2 +/- 12.3 minutes (P < .001) and 2.6 +/- 0.7 and 3.7 +/- 1.2 (P = .016). LIMITATIONS Single-center study and small sample size to evaluate overall safety. CONCLUSIONS Long-tube insertion for bowel obstruction with the ropeway method facilitated by transnasal ultrathin endoscopy was superior to conventional fluoroscopic placement with regard to overall procedure success, time required, and patient comfort.

De novo Crohn's disease following orthotopic liver transplantation: a case report and literature review.

The development of de novo Crohns disease (CD) after orthotopic liver transplantation (OLT) is rare, possibly due to the continuous use of immunosuppressive treatment. Although several cases of CD following OLT have been reported worldwide, there are currently so such cases in Japan. We herein report the case of a patient who newly developed CD after undergoing OLT for congenital biliary atresia. The patient subsequently underwent ileocecal resection and has since maintained clinical remission. This is the first report of this condition in Japan. We also review the literature concerning cases of de novo inflammatory bowel disease (IBD) developing after OLT, and discuss the causes of and role of immunosuppressive agents in treating IBD.

ATP-binding cassette subfamily B member 1 1236C/T polymorphism significantly affects the therapeutic outcome of tacrolimus in patients with refractory ulcerative colitis

Tacrolimus is now considered to be one of the main therapeutic options for refractory ulcerative colitis. Both cytochrome P‐450 3A5 (CYP3A5) and ATP‐binding cassette subfamily B member 1 (ABCB1) associated with tacrolimus metabolism are known to have several genetic polymorphisms. However, it remains controversial whether these polymorphisms affect the therapeutic efficacy for ulcerative colitis. We aimed to investigate the influence of both CYP3A5 and ABCB1 polymorphisms on the efficacy of tacrolimus in ulcerative colitis treatment under the tight dose‐adjusting strategy.

Two Cases of Diffuse Duodenitis Associated with Ulcerative Colitis

The upper gastrointestinal tract is not generally considered a target organ in ulcerative colitis (UC). However, several cases showing upper gastrointestinal involvement in UC have been reported. In this report, we present 2 rare cases of diffuse duodenitis accompanying pancolonic UC. Case patient 1 was a 44-year-old man who developed diffuse duodenitis shortly after colectomy and was successfully treated with mesalazine. Case patient 2 was a 25-year-old woman who developed diffuse duodenitis under a steroid-free condition and was successfully treated with prednisolone. The 2 patients had Helicobacter pylori-negative duodenitis that resembled colonic lesions of UC in both the endoscopic and histological findings. No evidence of Crohns disease was found in these cases. We diagnosed both cases as typical UC-associated diffuse duodenitis. The occurrence of gastrointestinal involvement in UC has been attracting attention because such lesions could potentially open a new window for studying the etiology and pathogenesis of UC. Further studies involving a large number of patients are needed to clarify whether the upper gastrointestinal tract is a target organ in UC.