Hirohisa Machida

Small Bowel Injury by Low-Dose Enteric-Coated Aspirin and Treatment With Misoprostol: A Pilot Study

BACKGROUND & AIMS With capsule endoscopy, the ulcerogenic effect of low-dose enteric-coated aspirin on the small bowel and the therapeutic effect of misoprostol on intestinal injury were evaluated. METHODS Eleven patients who developed gastric ulcers while undergoing low-dose enteric-coated aspirin therapy were enrolled. They continued aspirin therapy while taking proton pump inhibitors (PPIs) for 8 weeks to heal the gastric ulcers. Then misoprostol 200 microg 4 times a day was administered instead of PPIs for 8 weeks. When the patients could not tolerate misoprostol as a result of side effects, they received another 8 weeks of PPI therapy. RESULTS Capsule endoscopy performed after 8 weeks of PPI treatment identified red spots and mucosal breaks in 100% (11/11) and 90.9% (10/11) of patients, respectively. In 7 patients who completed the study protocol, misoprostol significantly decreased the median number of red spots and mucosal breaks, with complete disappearance of mucosal breaks in 4 patients. Intestinal lesions tended not to heal in 3 patients who discontinued misoprostol. CONCLUSIONS Low-dose enteric-coated aspirin frequently damages the small intestine, and misoprostol is effective in the treatment of aspirin-induced enteropathy.

A prospective, single-blind trial comparing wireless capsule endoscopy and double-balloon enteroscopy in patients with obscure gastrointestinal bleeding

BackgroundWireless capsule endoscopy (CE) and double-balloon enteroscopy (DBE) are new methods enabling diagnostic endoscopy of the entire small intestine. However, which of the two is superior is unclear. We therefore prospectively compared the clinical efficacy of CE and DBE.MethodsWe prospectively examined 32 patients with obscure gastrointestinal bleeding. CE preceded DBE by 1–7 days, and all patients underwent DBE twice, by antegrade and retrograde approaches, to evaluate the entire small intestine. Physicians evaluating the results of CE and DBE were blind to the results of the other method. We evaluated diagnosis, diagnostic yield of the two methods, and clinical outcomes.ResultsCE revealed abnormal findings in 29 (90.6%) of 32 patients. CE definitively or probably detected the sources of bleeding in 23 (71.9%) of the 32 patients, including angioectasias (eight), erosions (seven), ulcers (five), tumor (one), and hemorrhagic polyps (two). DBE definitely or probably detected the sources of bleeding in 21 (65.6%) of the 32 patients, including angioectasias (seven), erosions (four), ulcers (five), tumor (one), hemorrhagic polyps (two) and diverticula (two). CE yielded more abnormal findings than DBE (CE 90.6%, DBE 65.6%) (P = 0.032), although there were no significant differences in diagnostic yield between the methods. We were able to perform additional treatment or biopsy with DBE in 13 patients, including coagulation therapy (ten), endoscopic mucosal resection (one), biopsy (seven), and extraction of retained CE (two).ConclusionsOur results demonstrate the superiority of CE in detecting abnormal lesions, and the superiority of DBE in endoscopic management.

Narrow-band imaging (NBI) magnifying endoscopic classification of colorectal tumors proposed by the Japan NBI Expert Team.

Many clinical studies on narrow‐band imaging (NBI) magnifying endoscopy classifications advocated so far in Japan (Sano, Hiroshima, Showa, and Jikei classifications) have reported the usefulness of NBI magnifying endoscopy for qualitative and quantitative diagnosis of colorectal lesions. However, discussions at professional meetings have raised issues such as: (i) the presence of multiple terms for the same or similar findings; (ii) the necessity of including surface patterns in magnifying endoscopic classifications; and (iii) differences in the NBI findings in elevated and superficial lesions. To resolve these problems, the Japan NBI Expert Team (JNET) was constituted with the aim of establishing a universal NBI magnifying endoscopic classification for colorectal tumors (JNET classification) in 2011. Consensus was reached on this classification using the modified Delphi method, and this classification was proposed in June 2014. The JNET classification consists of four categories of vessel and surface pattern (i.e. Types 1, 2A, 2B, and 3). Types 1, 2A, 2B, and 3 are correlated with the histopathological findings of hyperplastic polyp/sessile serrated polyp (SSP), low‐grade intramucosal neoplasia, high‐grade intramucosal neoplasia/shallow submucosal invasive cancer, and deep submucosal invasive cancer, respectively.

Efficacy of magnifying chromoendoscopy for the differential diagnosis of colorectal lesions

Magnifying chromoendoscopy is an exciting new tool and offers detailed analysis of the morphological architecture of mucosal crypt orifices. In this review, we principally show the efficacy of magnifying chromoendoscopy for the differential diagnosis of colorectal lesions such as prediction between non‐neoplastic lesions and neoplastic ones, and distinction between endoscopically treatable early invasive cancers and untreatable cancers based on a review of the literature and our experience at two National Cancer Centers in Japan. Overall diagnostic accuracy by conventional view, chromoendoscopy and chromoendoscopy with magnification ranged from 68% to 83%, 82% to 92%, and 80% to 96%, respectively, and diagnostic accuracy of accessing the stage of early colorectal cancer using magnifying colonoscopy was over 85%. Although the reliability depends on the skill in magnifying observation, widespread applications of the magnification technique could influence the indications for biopsy sampling during colonoscopy and the indication for mucosectomy. Moreover, the new detailed images seen with magnifying chromoendoscopy are the beginning of a new period in which new optical developments, such as narrow band imaging system, endocytoscopy system, and laser‐scanning confocal microscopy, will allow a unique look at glandular and cellular structures.

NBI magnifying endoscopic classification of colorectal tumors proposed by the Japan NBI Expert Team (JNET)

Many clinical studies on narrow‐band imaging (NBI) magnifying endoscopy classifications advocated so far in Japan (Sano, Hiroshima, Showa, and Jikei classifications) have reported the usefulness of NBI magnifying endoscopy for qualitative and quantitative diagnosis of colorectal lesions. However, discussions at professional meetings have raised issues such as: (i) the presence of multiple terms for the same or similar findings; (ii) the necessity of including surface patterns in magnifying endoscopic classifications; and (iii) differences in the NBI findings in elevated and superficial lesions. To resolve these problems, the Japan NBI Expert Team (JNET) was constituted with the aim of establishing a universal NBI magnifying endoscopic classification for colorectal tumors (JNET classification) in 2011. Consensus was reached on this classification using the modified Delphi method, and this classification was proposed in June 2014. The JNET classification consists of four categories of vessel and surface pattern (i.e. Types 1, 2A, 2B, and 3). Types 1, 2A, 2B, and 3 are correlated with the histopathological findings of hyperplastic polyp/sessile serrated polyp (SSP), low‐grade intramucosal neoplasia, high‐grade intramucosal neoplasia/shallow submucosal invasive cancer, and deep submucosal invasive cancer, respectively.

Evaluation of Small Bowel Injury in Patients with Rheumatoid Arthritis by Capsule Endoscopy: Effects of Anti-Rheumatoid Arthritis Drugs

Background and Aim: The medical treatment of rheumatoid arthritis (RA) includes nonsteroidal anti-inflammatory drugs (NSAIDs), low-dose corticosteroids, and disease-modifying antirheumatic drugs (DMARDs). We evaluated the incidence of small bowel injury in RA patients who were taking anti-RA drugs with or without concomitant NSAIDs by capsule endoscopy. Methods: A total of 28 RA patients who took low-dose corticosteroids and/or DMARDs for more than 1 year were enrolled. Results: The incidence of red spots did not differ between the 2 groups: 14 of 16 patients (87.5%) in the NSAID group and 11 of 12 patients (91.7%) in the non-NSAID group. In contrast, the incidence of mucosal breaks was significantly higher in the NSAID group than in the non-NSAID group: mucosal breaks were detected in 13 of 16 patients (81.3%) and 4 of 12 patients (33.3%) in the NSAID and non-NSAID groups, respectively. In the NSAID group, mucosal breaks developed in users of preferential cyclooxygenase-2 inhibitors at a frequency similar to that in users of traditional NSAIDs. Conclusion: Patients taking anti-RA drugs may have an increased frequency of small bowel injury regardless of NSAID use, and NSAID use may be associated with an increased incidence of severe small bowel injury.

Usefulness of Non-Magnifying Narrow-Band Imaging in Screening of Early Esophageal Squamous Cell Carcinoma: A Prospective Comparative Study Using Propensity Score Matching

OBJECTIVES:The usefulness of non-magnifying endoscopy with narrow-band imaging (NBI; NM-NBI) in the screening of early esophageal squamous cell carcinoma (SCC) and high-grade intraepithelial neoplasia (HGIN) remains unclear. Here, we aimed to compare NM-NBI and chromoendoscopy with iodine staining (CE-Iodine) in terms of the diagnostic performance, and to evaluate the usefulness of NM-NBI in detecting early esophageal SCC.METHODS:We prospectively enrolled 202 consecutive patients (male/female=180/22; median age, 67 years) with high-risk factors for esophageal SCC. All patients received endoscopic examination with NM-NBI and CE-Iodine to screen for early esophageal SCC or HGIN. We conducted the examinations sequentially, and calculated the accuracy, sensitivity, and specificity through a per-lesion-based analysis. A propensity score matching analysis was performed to reduce the effects of selection bias, and we compared the respective outcomes according to NM-NBI and CE-Iodine after matching.RESULTS:The accuracy, sensitivity, and specificity of NM-NBI were 77.0, 88.3, and 75.2%, respectively, and those for unstained areas by CE-Iodine were 68.0, 94.2, and 64.0, respectively. The accuracy and specificity of NM-NBI were superior to those of CE-Iodine (P=0.03 and P=0.01, respectively). However, the sensitivity did not significantly differ between NM-NBI and CE-Iodine (P=0.67). The accuracy and specificity of NM-NBI before matching were superior to those of CE-Iodine after matching (P=0.04 and P=0.03).CONCLUSIONS:NM-NBI was useful and reliable for the diagnosis of esophageal SCC and can be a promising screening strategy for early esophageal SCC.

ENDOSCOPIC MUCOSAL RESECTION AND SUBMUCOSAL DISSECTION METHOD FOR LARGE COLORECTAL TUMORS

The goal of endoscopic mucosal resection (EMR) is to allow the endoscopist to obtain tissue or resect lesions not previously amenable to standard biopsy or excisional techniques and to remove malignant lesions without open surgery. In this article, we describe the results of conventional EMR and EMR using an insulation‐tipped (IT) electrosurgical knife (submucosal dissection method) for large colorectal mucosal neoplasms and discuss the problems and future prospects of these procedures. At present, conventional EMR is much more feasible than EMR using IT‐knife from the perspectives of time, money, complication, and organ preservation. However, larger lesions tend to be resected in a piecemeal fashion; and it is difficult to confirm whether EMR has been complete. For accurate histopathological assessment of the resected specimen en bloc EMR is desirable although further experience is needed to establish its safety and efficacy. Further improvements of in EMR with special knife techniques are required to simply and safely remove large colorectal neoplasms.

High Mobility Group Box 1 Promotes Small Intestinal Damage Induced by Nonsteroidal Anti-Inflammatory Drugs through Toll-Like Receptor 4

Release of high mobility group box 1 (HMGB1) from damaged cells, which is involved in many types of tissue injuries, activates inflammatory pathways by stimulating multiple receptors, including Toll-like receptor 2 (TLR2), TLR4, and receptor for advanced glycation end-products (RAGE). Our objective was to determine the role of HMGB1 in nonsteroidal anti-inflammatory drug (NSAID)-induced damage of the small intestine. Oral indomethacin (10 mg/kg) induced damage to the small intestine and was associated with increases in intestinal HMGB1 expression and serum HMGB1 levels. In wild-type mice, recombinant human HMGB1 aggravated indomethacin-induced small intestinal damage; enhanced the mRNA expression levels of tumor necrosis factor α (TNF-α), monocyte chemotactic protein 1, and KC; activated nuclear factor kappa B; and stimulated phosphorylation of the mitogen-activated protein kinases p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK). In contrast, blocking HMGB1 action with neutralizing antibodies prevented damage and inhibited both inflammatory cytokine overexpression and activation of these intracellular signaling pathways. TLR2-knockout (KO) and RAGE-KO mice exhibited high sensitivities to indomethacin-induced damage, similar to wild-type mice, whereas TLR4-KO mice exhibited less severe intestinal damage and lower levels of TNF-α mRNA expression. Exogenous HMGB1 aggravated the damage in TLR2- and RAGE-KO mice but did not affect the damage in TLR4-KO mice. Thus, our results suggest that HMGB1 promotes NSAID-induced small intestinal damage through TLR4-dependent signaling pathways.

Reduction of 15‐hydroxyprostaglandin dehydrogenase expression is an independent predictor of poor survival associated with enhanced cell proliferation in gastric adenocarcinoma

Prostaglandin (PG) E2 promotes gastrointestinal carcinogenesis and tumor progression. We determined the correlations between pattern of expression of 15‐hydroxyprostaglandin dehydrogenase (15‐PGDH), a catabolic enzyme for biological inactivation of PGE2, in gastric adenocarcinoma and various clinicopathological factors and patient outcome in an attempt to elucidate its biological significance. In 35 of 71 cases of gastric adenocarcinoma, expression of 15‐PGDH protein was reduced in tumor tissues. Multivariate analysis revealed reduction of 15‐PGDH expression to be an independent predictor of poor survival. The proportion of Ki67‐positive cells in 15‐PGDH‐negative adenocarcinoma was higher than that in 15‐PGDH‐positive adenocarcinoma. No differences were found in clinicopathological parameters between patients with cyclooxygenase‐2 (COX‐2)‐positive tumors and those with COX‐2 negative tumors. In an in vitro study, use of specific siRNA to silence 15‐PGDH or a specific inhibitor of 15‐PGDH enhanced cell proliferation in the gastric cancer cell line AGS, which expresses 15‐PGDH. These findings suggest that reduction of 15‐PGDH is an independent predictor of poor survival associated with enhancement of cell proliferation in gastric adenocarcinoma. (Cancer Sci 2009)