Multicenter epidemiological survey of pneumatosis intestinalis in Japan.

BACKGROUND: Pneumatosis intestinalis (PI) is a rare condition characterized by gas collection in the intestinal wall. We aimed to determine the etiology and affected segments associated with complications, treatment, and outcome. METHODS: We conducted a multicenter epidemiological survey using a standardized data collection sheet in Japan. Complicating PI was defined as strangulation or bowel necrosis, bowel obstruction, adynamic ileus, sepsis, shock, and massive gastrointestinal bleeding requiring blood transfusion. RESULTS: We enrolled 167 patients from 48 facilities. Multivariate analysis revealed that older age (adjusted OR, 1.05 and 95% confidence intervals [CI], 1.02-1.09, P = 0.0053) and chronic kidney disease (adjusted OR, 13.19 and 95% CI 1.04-167.62, P = 0.0468) were independent predictors of the small-bowel-involved type. Complicating PI was associated with the small-bowel-involved combined type (adjusted OR, 27.02 and 95% CI 4.80-152.01, P = 0.0002), the small-bowel-only type (adjusted OR, 3.94 and 95% CI 1.02-15.27, P = 0.0472), and symptomatic PI (adjusted OR, 16.24 and 95% CI 1.82-145.24, P = 0.0126). Oxygen therapy was performed in patients with a past history of bowel obstruction (adjusted OR, 13.77 and 95% CI 1.31-144.56, P = 0.0288) and surgery was performed in patients with complicating PI (adjusted OR, 8.93 and 95% CI 1.10-72.78, P = 0.0408). Antihypertensives (adjusted OR, 12.28 and 95% CI 1.07-140.79, P = 0.0439) and complicating PI (adjusted OR, 11.77 and 95% CI 1.053-131.526; P = 0.0453) were associated with exacerbation of PI. The complicating PI was the only indicator of death (adjusted OR, 14.40 and 95% CI 1.09-189.48, P = 0.0425). DISCUSSION: Small-bowel-involved type and symptomatic PI were associated with complications which were indicators of poor prognosis.

Early Intervention with Infliximab Prevents Reoperation in Crohn's Disease: A Single-Center Retrospective Analysis.

BACKGROUND/AIMS: We aimed to evaluate the prognostic factors that can aid in the prevention of first and second surgeries in patients with Crohn's disease (CD). METHODS: The clinical records of 115 patients with CD whose disease onset was between January 1987 and July 2012 were retrospectively investigated. The cumulative rate of bowel resection for CD-related intestinal manifestations following onset until the first surgery and the cumulative rate of reoperation following the first to second surgeries were estimated using the Kaplan-Meier method, and the relationship to each factor was statistically analyzed using the log-rank test. The background factors that influenced the cumulative rate of the first surgery and reoperation were evaluated using univariate and multivariate analyses. RESULTS: The cumulative bowel resection rate was significantly higher in patients with ileocolitis-type CD (p = 0.0018) and in those with CD with smoking habits (p = 0.0315). And the cumulative reoperation rate was significantly higher in patients with ileocolitis-type CD (p = 0.0161) and those without early intervention with infliximab (p = 0.0161). CONCLUSIONS: Ileocolitis-type CD and smoking habit might be initiating factors for bowel resection due to CD-related intestinal manifestations. Early intervention with infliximab likely prevents reoperation for CD recurrence.

Anal cushion lifting method is a novel radical management strategy for hemorrhoids that does not involve excision or cause postoperative anal complications.

AIM: To describe the anal cushion lifting (ACL) method with preliminary clinical results. METHODS: Between January to September 2007, 127 patients who received ACL method for hemorrhoid was investigated with informed consent. In this study, three surgeons who specialized in anorectal surgery performed the procedures. Patients with grade two or more severe hemorrhoids according to Goligher's classification were considered to be indicated for surgery. The patients were given the choice to undergo either the ACL method or the ligation and excision method. ACL method is an original technique for managing hemorrhoids without excision. After dissecting the anal cushion from the internal sphincter muscle, the anal cushion was lifted to oral side and ligated at the proper position. Clinical characteristics and outcomes of patients were recorded including complications after surgery. RESULTS: A total of 127 patients were enrolled. Their median age was 42 (19-84) years, and 74.8% were female. In addition, more than 99% of the patients had grade 3 or worse hemorrhoids. The median follow-up period was 26 (0-88) mo, and the median operative time was 15 (4-30) min. After surgery, analgesics were used for a median period of three days (0-21). Pain control was achieved using extra-oral analgesic drugs, although some patients required intravenous injections of analgesic drugs. The median duration of the patients' postoperative hospital stay was 7 (2-13) d. A total of 10 complications (7.9%) occurred. Bleeding was observed in one patient and was successfully controlled with manual compression. Urinary retention occurred in 6 patients, but it disappeared spontaneously in all cases. Recurrent hemorrhoids developed in 3 patients after 36, 47, and 61 mo, respectively. No anal stenosis or persistent anal pain occurred. CONCLUSION: We consider that the ACL method might be better than all other current methods for managing hemorrhoids.

Safety of gastrointestinal endoscopic biopsy in patients taking antithrombotics.

BACKGROUND AND AIM: 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. METHODS: Consecutive patients receiving antithrombotics who underwent GI endoscopy from August 2012 to August 2013 were enrolled. Adverse events and endoscopic hemostasis after biopsy were evaluated. PT-INR level was measured in patients taking warfarin the day before endoscopy. RESULTS: Among 7939 patients undergoing endoscopy, 1034 patients (13.0%, 706 men and 328 women, average age 72.8 years) were receiving antithrombotics. Antithrombotics included aspirin (44.8%), warfarin (34.7%), thienopyridine (16.1%), cilostazol (10.3%), dabigatran (4.8%) etc. PT-INR levels in patients taking warfarin were >3.0 in 13 patients (4.3%), between 2.5 and 3.0 in 18 patients (6.0%), <2.5 in 269 patients (89.7%). Two hundred and six patients received endoscopic biopsy while taking aspirin (51.2%), warfarin (22.8%), and thienopyridine (13.6%). Endoscopic hemostasis was required in three patients after endoscopic biopsy (spraying thrombin in two patients, spraying thrombin and clipping in one patient). There were no major complications. The incidence of endoscopic hemostasis after biopsy in patients without antithrombotic cessation was not significantly different than in the controls not taking antithrombotics (1.5% vs 0.98%, P = 0.51). CONCLUSION: Endoscopic biopsy did not increase the bleeding risk despite not stopping antithrombotics prior to biopsy even among patients taking warfarin whose PT-INR was within the therapeutic range.

[Relationship between visceral fat and development of colorectal neoplasms using computed tomographic colonography and adipocytokine levels].

We evaluated the relationship between colorectal neoplasms and visceral obesity using computed tomographic colonography and adipocytokine levels. We included 123 patients and classified them into four groups as per computed tomographic colonography: no lesion (NL; n=40), adenomatous polyp (polyp; n=41), early colorectal cancer (eCRC; n=21), and advanced CRC (aCRC; n=21). We also measured the patients' serum metabolic markers and adipocytokine levels. The visceral adiposity index in the polyp and eCRC groups was significantly higher than that in the NL group. Visceral obesity is an important risk factor for the development of colonic polyps. Computed tomographic colonography could be a useful examination technique not only for diagnosis of colorectal neoplasms but also for simultaneous evaluation of visceral obesity.

Clinical relevance of patency capsule combined with abdominal ultrasonography to detect small bowel strictures.

BACKGROUND: PillCam patency capsule (PC) is a novel and radiofrequency identification tag-free device that remains intact in the gastrointestinal tract for 30-33 h after ingestion and then disintegrates. The aim of this study was to determine the clinical relevance of PC combined with abdominal ultrasonography as a reliable indicator of functional patency. PATIENTS AND METHODS: The study was prospective and PillCam PC was administered to consecutive patients with known or suspected small bowel strictures. PC was verified if it was excreted intact in 33 h after administration. Following excretion failure and radiograph detection in the pelvic cavity, ultrasonography was used to detect the PC in relation to the stricture. RESULTS: The participants were 52 patients with known or suspected small bowel strictures (58% women, mean age 51 years, including 32 with or suspected Crohn's disease). Twenty-two patients (42.3%) retrieved PC in the stool within 33 h after ingestion. Radiograph identified the four PCs in the colon and eight were not observed. Ultrasonography precisely judged all 17 PCs retained including six PCs at the proximal side of small bowel stricture in the patients considered ineligible for capsule endoscopy (CE). In all eligible patients, CE passed through the small intestine without incident. CONCLUSION: PillCam PC combined with ultrasonography before CE appears to be a reliable indicator of functional patency to predict and minimize the risk of impaction in suspected or even known cases with small bowel stricture.

Application of fecal hemoglobin-haptoglobin complex testing for small bowel lesions.

OBJECTIVE: Fecal hemoglobin-haptoglobin (Hb-Hpt) complex testing is theoretically superior to immunochemical fecal occult blood test detecting human hemoglobin (Hb), as Hb-Hpt is more stable compared to Hb during passage through the gastrointestinal (GI) tract. The aim was to examine the role of fecal Hb-Hpt complex testing in predicting small bowel lesions detected by video capsule endoscopy (VCE). MATERIALS AND METHODS: Stools from patients undergoing small bowel VCE for obscure GI bleeding (OGIB) without ongoing overt bleeding were included. Two stool specimens were obtained on different days just before VCE to measure Hb-Hpt complex by ELISA and Hb by latex agglutination turbidimetric immunoassay. RESULTS: Seventy-six patients (39 men and 37 women, average age 66 years) with suspected small bowel lesions entered. Median Hb-Hpt complex and Hb levels were significantly higher (p<0.001) in those with small bowel lesions compared to those without. Using the suitable cutoff points (Hb>0 ng/ml and Hb-Hpt complex>5 ng/ml), the sensitivity and specificity of the Hb-Hpt complex test to predict small bowel lesions were 71.4% and 73.3%, and those of the Hb test were 61.2% and 89.3%. Small bowel lesions were found in 58.3% with only Hb-Hpt complex positive results (15.8% of total subjects) compared to 83.3% when both were positive (55.3% of total). CONCLUSIONS: Measuring fecal Hb-Hpt complex in addition to Hb may be useful to predict the presence of small bowel lesions in patients with OGIB.

S100A expression and interleukin-10 polymorphisms are associated with ulcerative colitis and diarrhea predominant irritable bowel syndrome.

BACKGROUND: Both ulcerative colitis (UC) and diarrhea-predominant irritable bowel syndrome (IBS-D) are associated with alterations in enteric serotonin (5-HT) signaling. AIMS: The purpose of this study was to compare the rectal and sigmoid colonic mucosal expression of S100A proteins and functional polymorphisms of the 5-HT transporter (5HTT) and interleukin-10 genes in patients with IBS-D or UC with healthy controls. METHODS: mRNA expression of S100 proteins was measured in sigmoid and rectal biopsies and in rectal epithelium isolated by laser-captured microdissection. Leucocyte DNA was analyzed by PCR-based reaction fragment length polymorphisms and direct sequencing. Clinical symptoms were assessed by the self-rating depression scale and by the gastrointestinal symptom rating scale. RESULTS: Fifty patients with IBS-D, 56 with UC and 50 healthy controls were studied. Colonic mucosal expression of S100A8 and S100A9 in UC was significantly higher than in IBS or controls and correlated with the UC disease activity index (r = 0.65, p < 0.001). S100A10 expression in the rectal epithelium of the IBS patients was significantly higher (0.643 vs. 0.402, p = 0.01) than in controls and correlated with the SDS scores (r = 0.41, p = 0.002). The frequency of IL10-819 CC genotype was significantly higher in IBS-D (10.7 vs. 0 %, p = 0.047) and UC (16 vs. 0 %, p = 0.007) than that in controls. CONCLUSION: Overexpression of S100A10 in the rectum may play a role in IBS as it is involved in modulating 5-HT1B receptors. The IL10-819 CC is a candidate genotype for both IBS and UC in Japanese.

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.

An evaluation of the performance of a novel stick-type kit for rapid detection of Helicobacter pylori antibodies in urine.

BACKGROUND: ODK-0702 is a stick-type urinary Helicobacter pylori (H. pylori) antibodies detection kit, developed to improve the original housing type urinary H. pylori antibodies detection kit "RAPIRUN H. pylori Antibody". This stick-type kit is designed for the efficient daily medical practice at hospital or clinic, public or school health checkup, to detect H. pylori infection. The aim of this study was to evaluate the performance and correlation of this kit with the original kit and the ELISA kit. METHODS: Control kits were "RAPIRUN H. pylori Antibody" (Kit A) and "URINELISA H. pylori Antibody" (Kit B). Urine samples were obtained from 249 subjects scheduled for upper endoscopy, 99 subjects suspected of having upper gastrointestinal disease, and 150 subjects receiving health checkups. Rates of agreement in results between ODK-0702 and the control kits were investigated. RESULTS: High agreement rates of 98.4% (245/249) and 88.8% (221/249) were found between ODK-0702 and the kits, Kit A and B, respectively. In patients, the agreement rates of ODK-0702 as compared to Kit A and B were 99.0% (98/99) and 88.9% (88/99), respectively. In control subjects, the agreement rates of ODK-0702 as compared to Kit A and B were 98.0% (147/150) and 88.7% (133/150), respectively. CONCLUSIONS: ODK-0702 enabled rapid testing within 15 minutes and showed equivalent performance as control kits, being clinically very useful in the diagnosis of H. pylori infection.

Changes of upper gastrointestinal symptoms and endoscopic findings in Japan over 25 years.

BACKGROUND AND AIMS: In Japan, the prevalence of Helicobacter pylori infection has decreased recently, but there has been little longitudinal research on the changes of symptoms and endoscopic findings over many years. The aim of this study was to evaluate the changes in endoscopic findings and symptoms over time in patients undergoing upper gastrointestinal endoscopy for assessment of upper abdominal symptoms. METHODS: Over a period of 25 years, between 1981 and 2005, we performed three investigations (1981-2, 1990-1 and 2004-5) on the symptoms and endoscopic findings of patients undergoing endoscopy at Kawasaki Medical School Hospital for the assessment of upper abdominal symptoms. RESULTS: The most common complaint for all ages was "discomfort and/or pain". Over time, the percentage of patients complaining of "heartburn" increased almost 5-fold. With respect to endoscopic findings, the prevalence of peptic ulcers decreased, whereas the detection of no abnormalities and the detection of erosive esophagitis increased. CONCLUSION: In the future in Japan, there will be fewer patients with peptic ulcers and more patients with gastro-esophageal reflux disease or dyspeptic patients who display no endoscopic abnormal findings.

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

BACKGROUND: Since 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. METHODS: The 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. RESULTS: There 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. CONCLUSIONS: RAPID(®) 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.

Renin-angiotensin system associated with risk of upper GI mucosal injury induced by low dose aspirin: renin angiotensin system genes' polymorphism.

BACKGROUND: We have previously shown that co-treatment of angiotensin type 1 receptor (AT1R) blocker (ARB) or angiotensin converting enzyme (ACE) inhibitor seem to reduce peptic ulcer among patients taking low dose aspirin. It is reported that a series of renin-angiotensin system (RAS) gene polymorphisms significantly influence the rate of the gene transcription. AIM: The aim of this study was to examine the genotypes of RAS genes related to the risk of peptic ulcer and ulcer bleeding among patients taking low dose aspirin. METHODS: Patients taking 100 mg of aspirin who were planning to undergo endoscopy for surveillance or who had history of recent upper GI ulcer bleeding were included. ACE (Ins/Del), angiotensinogen (AGT; G-217A, A-20C, A-6G, T174 M, M235T), and AT1R (T-713G, C-521T, A1166C) genotypes were determined by PCR or PCR-RFLP. RESULTS: Four hundred twenty-five patients were enrolled including 68 patients with peptic ulcer and 20 patients with ulcer bleeding. Co-treatment of ARB was significantly associated with peptic ulcer and ulcer bleeding. AGT-20 CC (adjusted OR 4.94, 95% CI 1.21-20.2) was significantly associated with ulcer bleeding. The CC genotype of AT1R-521 was significantly associated with peptic ulcer only in the subgroup taking neither ACE inhibitor nor ARB. CONCLUSIONS: Co-treatment of ARB reduces peptic ulcer and bleeding among patients taking low dose aspirin. RAS may play an important role in the development of upper GI mucosal injury induced by low dose aspirin.

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

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.

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 Barrett's 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.

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.

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-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) have been associated with development of peptic ulcer or gastric cancer. In a recent investigation, carriage of the IL-1beta-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.

Rectal mucosal prolapse syndrome as an unusual gastrointestinal manifestation of Sjögren's syndrome: a case report.

INTRODUCTION: Rectal mucosal prolapse syndrome, histologically characterized by fibromuscular obliteration in the lamina propria, hyperplastic glands and thickened muscularis mucosa, causes rectal bleeding. Sjögren's syndrome is an autoimmune exocrinopathy that chiefly destroys the salivary and lacrimal glands by lympho-plasmacytic infiltration. Although various gastrointestinal manifestations have been reported in patients with Sjögren's syndrome, there have not been to our knowledge any case reports to date of rectal mucosal prolapse syndrome in association with Sjögren's syndrome. CASE PRESENTATION: A 68-year-old Japanese woman with Sjögren's syndrome and long-term constipation consulted our hospital because of rectal bleeding. Because of dysphagia and xerostomia, she had consistently refused recommendations to take oral medicines including cathartics. Therefore, she frequently strained excessively during defecation. Colonoscopy and radiological examinations disclosed eroded flat protrusions of the rectum. Microscopic examination demonstrated inflamed mucosa with elongated tortuous glands and fibromuscular obliteration. Based on these findings, a diagnosis of rectal mucosal prolapse syndrome was made. Prohibition of straining during defecation and sulfasalazine suppository use were effective. CONCLUSION: This case highlights the importance of defecation control in patients with Sjögren's syndrome. In the case presented, rectal mucosal prolapse syndrome following long-term excessive straining during defecation caused rectal bleeding. Clinicians should consider rectal mucosal prolapse syndrome as a gastrointestinal manifestation of Sjögren's syndrome.

The preventive factors for aspirin-induced peptic ulcer: aspirin ulcer and corpus atrophy.

PURPOSE: Interleukin-1beta (IL-1beta) polymorphisms are associated with peptic ulcer and atrophic gastritis. This study aimed to examine effects of corpus atrophy and the genotypes of genes related to peptic ulcer, including IL-1beta, on risk of aspirin ulcer. METHODS: 232 patients taking 100 mg of aspirin for cardiovascular diseases, of whom 40 had peptic ulcer, were enrolled. IL1beta, interleukin-1 receptor antagonist (IL-1RN), tumor necrosis factor (TNF)-alpha, cyclooxygenase (COX)-1, cytochrome p450 2C9 (CYP2C9), UDP-glucuronosyltransferase (UGT1A6) genotypes were determined, and serum pepsinogen levels were measured. RESULTS: The polymorphisms of IL-1beta-511/-31 were significantly associated with peptic ulcer, but other genotypes were not. Serum pepsinogen I and II levels and I/II ratio were significantly higher in the ulcer group than in the non-ulcer group. Taking PPI [adjusted odds ratio (OR), 0.09; 95% confidence interval (CI), 0.02-0.39], pepsinogen I of less than 50 ng/ml (OR, 0.24; 95% CI, 0.10-0.56) and IL-1beta-511 T carrier (OR, 0.42; 95% CI, 0.18-0.93) were significantly associated with peptic ulcer. CONCLUSIONS: Hypoacidity related to corpus atrophy as well as taking PPI seems to be preventively associated with development of peptic ulcer among low dose aspirin users.