Ken-ichi Tarumi

GI involvement in Henoch-Schönlein purpura

BACKGROUND The diagnosis of Henoch-Schönlein purpura is difficult, especially when abdominal symptoms precede cutaneous lesions. The aim of this study was to determine the distribution of GI involvement in Henoch-Schönlein purpura. METHODS Endoscopic or radiographic findings throughout the entire GI tract were retrospectively reviewed for 7 patients with Henoch-Schönlein purpura. Histopathologic findings were analyzed and correlated with findings at EGD and colonoscopy. OBSERVATIONS The duodenum and small intestine were most frequently involved (6 patients, each site). Contrast radiography of the small intestine demonstrated thickened mucosal folds or small barium flecks. Findings at EGD were multiple irregular ulcers, mucosal redness and petechiae in the duodenum. In 4 patients, the second part of the duodenum was predominantly affected. Ulcerating lesions accompanied by hematoma-like protrusions were detected in 4 patients in whom leukocytoclastic vasculitis was proven histopathologically. CONCLUSIONS EGD appears to have the greatest diagnostic utility in patients suspected to have Henoch-Schönlein purpura with GI involvement.

Upper gastrointestinal ulcer in Japanese patients taking low-dose aspirin

BackgroundThere are few studies on the association of the risks of upper gastrointestinal (GI) ulcer induced by aspirin combined with other medicines. We investigated the association between peptic ulcer and clinical parameters, including Helicobacter pylori infection and combinations of medicines.MethodsPatients taking 100 mg aspirin for cardiovascular diseases who were planning to undergo endoscopy were enrolled. Serum H. pylori IgG antibody was measured.ResultsA total of 305 patients were enrolled, and 38 patients (12.4%) had ulcer lesions. Sex, smoking, drinking, body mass index, endoscopic findings for gastric atrophy (open type), or presence of H. pylori were not significantly associated with ulcer lesions. Cotreatment with anticoagulants [ticlopidine, 34.2% vs. 21.3%; adjusted odds ratio (OR), 3.1; 95% confidence interval (CI), 1.4–7.1; ticlopidine plus warfarin, 13.2% vs. 3.7%; adjusted OR, 4.4; 95% CI, 1.3–15], proton pump inhibitor (PPI 5.3% vs. 34.8%; adjusted OR, 0.10; 95% CI, 0.02–0.43), and antihypertensive medicine were significantly associated with peptic ulcer. Among antihypertensive medicines, AT1 receptor blocker and angiotensin-converting enzyme (ACE) inhibitor tended to be associated with upper GI ulcer.ConclusionsPPI was superior to H2-receptor antagonist for prevention of peptic ulcer, and cotreatment with AT1 receptor blocker or ACE inhibitor seemed to reduce peptic ulcer among patients taking low-dose aspirin.

Aspirin-induced peptic ulcer and genetic polymorphisms.

There are a few studies of the association between genetic polymorphisms and the risks of acetylsalicylic acid (aspirin)‐induced ulcer or its complications. Two single nucleotide polymorphisms (SNP) of cyclooxygenase‐1 (COX‐1), A‐842G and C50T, exhibited increased sensitivity to aspirin and had lower prostaglandin synthesis capacity, lacking statistical significance in the association with bleeding peptic ulcer. A recent Japanese study indicated that the number of COX‐1‐1676T alleles was a significant risk factor for peptic ulcer in users of non‐steroidal anti‐inflammatory drugs (NSAIDs). There are some genetic polymorphisms for aspirin resistance, such as platelet membrane glycoproteins, thromboxane A2 (TXA2) receptor, platelet activating factor acetylhydrolase and coagulation factor XIII; however, data on the frequency of gastrointestinal (GI) events in these variants are lacking. Carrying the CYP2C9 variants is reported a significantly increased risk of non‐aspirin NSAID‐related GI bleeding. The polymorphisms of interleukin‐1β (IL‐1β) and tumor necrosis factor‐α (TNF‐α) have been associated with development of peptic ulcer or gastric cancer. In a recent investigation, carriage of the IL‐1β‐511 T allele was significantly associated with peptic ulcer among low‐dose aspirin users. Hypoacidity in corpus gastritis related to polymorphisms of pro‐inflammatory cytokines seems to reduce NSAIDs or aspirin‐related injury. Data on which polymorphisms are significant risk factors for GI events in aspirin users are still lacking and further large‐scale clinical studies are required.

Safety of gastrointestinal endoscopic biopsy in patients taking antithrombotics

Current Japanese gastrointestinal (GI) endoscopic guidelines permit endoscopic biopsy without cessation of antiplatelet agents and warfarin in patients with a therapeutic range of prothrombin time–international normalized ratio (PT‐INR) levels, although the evidence levels are low. We evaluated the safety of endoscopic biopsy in patients currently taking antithrombotics.

Evaluation of RAPID® 5 Access software for examination of capsule endoscopies and reading of the capsule by an endoscopy nurse

BackgroundSince capsule endoscopy (CE) is time consuming, one possible cost-effective strategy could be the use of an expert endoscopic assistant and available software to select images. Aims were to examine the clinical utility of RAPID® 5 Access software and find the optimum setting mode for reading. We also evaluated whether a nurse could preview the CE video and detect significant lesions accurately.MethodsThe capsule images in 14 volunteers with known mucosal injury induced by low dose aspirin and in 30 patients who were known to have a variety of significant lesions were selected. Using three setting modes of RAPID® 5 Access software, the detection rate and reading time for CE images by two well-trained physicians and one expert nurse were compared.ResultsThere was no significant difference in detection rate among the three readers. The detection rate using Quickview RAPID® 5 Access was significantly higher than that using RAPID® Reader version 4.1. Comparison among the three modes of RAPID® 5 Access showed that auto mode as well as displaying a single image at 12 fps was superior in the detection rate of denuded redness, while its reading time was longer compared to the other modes. Some significant lesions were not detected by using Quickview and Quadview modes.ConclusionsRAPID® 5 Access improves diagnostic yield, reducing reading time; however, it is still unacceptable because of the diagnostic miss rate and may be useful as an ancillary reading tool. Developing further improved software and training expert assistants for reading capsule images are necessary.

Combination of low-dose aspirin and thienopyridine exacerbates small bowel injury.

Abstract Objective. Antithrombotics is increasingly being used for cardiovascular prevention. In more recent studies, small bowel injury and enteropathy associated with low-dose aspirin are increasingly being recognized. Aim of this study was to evaluate small bowel injury using video capsule endoscopy (VCE) in obscure gastrointestinal bleeding (OGIB) patients taking low-dose aspirin including other antithrombotics. Material and methods. This is a retrospective review of chronic users of antithrombotics who underwent VCE for suspected small bowel bleeding. Small bowel mucosal injury was evaluated using VCE findings. Results. Fifty-four OGIB patients (36 men and 18 women, mean age 72.4 years) underwent VCE from January 2007 to May 2009. Twenty-two patients were taking 100 mg of enteric-coated aspirin (aspirin group), 8 taking thienopyridine, (ticlopidine or clopidogrel, thienopyridine group), 13 taking aspirin combined with thienopyridine (combined group), and 11 taking warfarin (warfarin group). The mucosal injury, especially ulcers were most frequently detected in the combined group (46.2%, p = 0.01) among the four groups. The median number of redness lesions in the combined group was the highest among the four groups and was significantly higher than that in the warfarin group. The lesions of redness or small erosions in the aspirin and the combined groups tended to exist in the proximal part of small bowel. Conclusions. Combination of low-dose aspirin therapy and thienopyridine may exacerbate small bowel injury, and the preventive strategies should be established.

Long-Term Outcome after Double-Balloon Endoscopy in Patients with Obscure Gastrointestinal Bleeding

Background and Aims: There are limited data concerning the clinical outcome of patients with obscure gastrointestinal bleeding (OGIB) after double-balloon endoscopy (DBE). The aim of the present study was to evaluate the long-term outcome of patients with OGIB after DBE. Patients and Methods: Eighty-seven consecutive patients with OGIB (47 men and 40 women; mean age 65.3 years) underwent DBE between July 2006 and December 2009. The criteria for assessment included documented iron deficiency anemia/occult or obscure small intestinal bleeding, and overt small intestinal bleeding. They were followed for a mean period of 41.4 months after DBE, and were divided into two groups according to their outcome, that is a good clinical course group (GC group) and a poor clinical course group (PC group). The clinical characteristics associated with rebleeding after DBE were analyzed by comparison of these two groups. Results: The source of bleeding was identified in 40 patients (46.0%) and endoscopic treatment was required in 21 of them (52.5%). The most frequent source of bleeding was ulcers/erosions (18.4%). During the follow-up period, 39 patients (44.8%) experienced bleeding and/or persistent iron deficiency anemia after DBE, while 48 patients did not. There were no significant differences of clinical characteristics between the two groups. However, there were more patients with diverticular bleeding in the GC group than the PC group, and there were significantly more patients with treatable small intestinal tumors/polyps in the GC group. There were also more patients with normal DBE findings in the GC group. Conclusion: This study demonstrated that the rebleeding rate after DBE varies depending on the source of bleeding.

Expression of Sonic hedgehog (SHH) and CDX2 in the columnar epithelium of the lower oesophagus

BACKGROUND Decreases in Sonic hedgehog (SHH) and CDX2 expression are associated with atrophy and intestinal metaplasia in the gastric mucosa. The pathogenesis of development of Barretts oesophagus is still unclear. OBJECTIVE To examine the gene expression of CDX2 and SHH and their signalling pathways in the columnar epithelium and the association with endoscopic appearance, gastric pH or bile acids. SUBJECTS/METHODS Sixty-three patients with metaplastic columnar epithelium of the lower oesophagus were studied. Whole biopsy specimens and microdissected tissues were examined for messenger RNA. RESULTS BMP4 expression was significantly higher in patients with tubular mucosal patterns of columnar epithelium visualised by Narrow Band Imaging with magnification. The expression of SHH was significantly lower and that of CDX2 was higher in the goblet columnar epithelium than in non-goblet columnar epithelium. CDX2 expression was significantly higher in the patients with hypoacidity than in the others. BMP4 and PTCH1 expression was significantly higher in the group with higher concentrations of deoxycholic acid than in the group with lower concentrations. CONCLUSIONS SHH might be the initial factor inducing columnar metaplasia, and subsequent or simultaneous BMP4 stimuli might induce the CDX2 expression that causes goblet-cell metaplasia.

Analysis of small-bowel capsule endoscopy reading by using Quickview mode: training assistants for reading may produce a high diagnostic yield and save time for physicians.

Goal: The aim was to investigate the clinical utility of RAPID Access 6.5 Quickview software and to evaluate whether preview of the capsule endoscopy video by a trained nurse could detect significant lesions accurately compared with endoscopists. Background: As reading capsule endoscopy is time consuming, one possible cost-effective strategy could be the use of trained nonphysicians or newly available software to preread and identify potentially important capsule images. Study: The 100 capsule images of a variety of significant lesions from 87 patients were investigated. The minimum percentages for settings of sensitivity that could pick up the selected images and the detection rate for significant lesions by a well-trained nurse, two endoscopists with limited experience in reading, and one well-trained physician were examined. Results: The frequency of the selected lesions picked up by Quickview mode using percentages for sensitivity settings of 5%, 15%, 25%, and 35% were 61%, 74%, 93%, and 98%, respectively. The percentages for sensitivity significantly correlated (r=0.78, P<0.001) with the reading time. The detection rate by the nurse or the well-trained physician was significantly higher than that by the physician with limited capsule experience (87% and 84.1% vs. 62.7%; P<0.01). The clinical use of Quickview at 25% did not significantly improve the detection rate. Conclusions: Quickview mode can reduce reading time but has an unacceptably miss rate for potentially important lesions. Use of a trained nonphysician assistant can reduce physician’s time and improve diagnostic yield.

Association of SLCO1B1*1b with peptic ulcer amongst Japanese patients taking low-dose aspirin

BACKGROUND In the recent case-control study, we showed an inverse association between peptic ulcer and angiotensin type 1 receptor (AT1R) blockers (ARBs) or HMG-Co A reductase inhibitors (statins). The aim was to evaluate whether the genotypes of uptake and efflux transporters of ARBs and statins relate to the presence of peptic ulcer and/or ulcer bleeding associated with aspirin use. METHODS Patients taking 100mg of enteric-coated aspirin for cardiovascular diseases who also participated in endoscopic surveillance were studied. SLCO1B, ABCC2, ABCG2, and MDR1 genotypes were determined by PCR or PCR-RFLP. RESULTS 492 patients enrolled including 78 with peptic ulcer. The frequencies of the SLCO1B1 521TT genotype were significantly higher in the ulcer group (p=0.006) compared to the controls. After adjustment for significant factors, the SLCO1B1 1b haplotype was significantly associated with peptic ulcer (OR, 3.64; 95% CI, 1.81-7.29). CONCLUSIONS SLCO1B1 1b haplotype may identify patients at increased risk for aspirin-induced peptic ulcer.