Risk factors for postoperative bleeding and early death in percutaneous endoscopic gastrostomy: A multicenter retrospective study.

BACKGROUND AND AIM: Comprehensive reports on the risk factors for bleeding and early death after percutaneous endoscopic gastrostomy (PEG) are limited. In this multicenter study, we retrospectively investigated the risk factors for bleeding and early death after PEG. METHODS: Patients (n = 1234) who underwent PEG between 2015 and 2020 at Osaka Medical and Pharmaceutical University and its affiliated hospitals (11 institutions in total) were evaluated for postoperative bleeding and early death (within 60 days) after PEG according to patient characteristics, construction method, medical history, medications, preoperative hematological findings, and perioperative adverse events. Multivariate logistic regression was performed to identify independent predictors of bleeding and early death after PEG. RESULTS: The risk factors for bleeding after PEG were PEG tube insertion using the modified introducer method (odds ratio [OR], 4.37; P = 0.0003), low platelet count (OR, 0.99; P = 0.014), antiplatelet therapy (OR, 2.11; P = 0.036), and heparinization (OR, 4.50; P = 0.007). Risk factors for early death were low body mass index (BMI) (OR, 0.89; P = 0.015), low serum albumin levels (OR, 0.50; P = 0.035), and comorbidity of active cancer (OR, 4.03; P < 0.0001). There was no significant association between bleeding and early death after PEG. CONCLUSIONS: We identified several risk factors for bleeding and early death after PEG. Risk factors for bleeding were PEG tube insertion using the modified introducer method, low platelet count, antiplatelet therapy, and heparinization. Risk factors for early death were low BMI, low serum albumin levels, and comorbidity of active cancer.

Preventive effect of ecabet sodium on low-dose aspirin-induced small intestinal mucosal injury: a randomized, double-blind, pilot study.

BACKGROUND: We aimed to investigate how high-dose ecabet sodium affects low-dose aspirin-induced small intestinal mucosal injury in healthy volunteers. METHODS: Healthy volunteers were enrolled randomly into one of two groups with the following drug regimens for 2 weeks: group A, low-dose aspirin once per day and group B, low-dose aspirin and 4.0 g of ecabet sodium. Small bowel capsule endoscopy was performed before and 2 weeks after low-dose aspirin administration. RESULTS: A significant difference was found in the median number [range] of small intestinal lesions between baseline and two weeks after low-dose aspirin administration in group A (baseline: 1 [0-5], after: 5 [1-11]; p = 0.0059) but not in group B (baseline: 0.5 [0-9], after: 3 [0-23]; p = 0.0586). In group B, although the median number [range] of lesions in the first tertile of the small intestine did not increase two weeks after low-dose aspirin administration (baseline: 0 [0-4], after: 1.5 [0-8]; p = 0.2969), the number of lesions in the second and third tertiles of the small intestine increased significantly (baseline: 0 [0-5], after: 2 [0-15]; p = 0.0469). CONCLUSIONS: Ecabet sodium had a preventive effect on low-dose aspirin-induced small intestinal mucosal injury in the upper part of the small intestine. TRIAL REGISTRATION: ISRCTN 99322160 , 01/10/2018.

Investigation of small intestinal lesions in dialysis patients using capsule endoscopy.

INTRODUCTION: Although gastrointestinal hemorrhage is an important complication for dialysis patients, the details of many points remain unclear with regard to small intestinal lesions. METHODS: Capsule endoscopy was performed in fecal occult blood-positive dialysis (n =16) and non-dialysis (n = 20) patients after upper and lower gastrointestinal endoscopies failed to reveal hemorrhagic lesions. FINDINGS: Erosive lesions were observed in 50.0% (8/16) and 25.0% (5/20) of the dialysis and non-dialysis groups, respectively. Vascular lesions were observed in 62.5% (10/16) and 25.0% (5/20), respectively. Vascular lesions were observed at a significantly higher rate in the dialysis patients (P = 0.041), but no significant difference was noted in erosive lesions (P = 0.188). Of patients taking proton pump inhibitor (PPI), Non-Steroidal Anti-Inflammatory Drugs, and antiplatelet drugs, only oral PPI administration was associated with vascular lesions (P = 0.02). DISCUSSION: In dialysis patients, vascular lesions are the most common among small intestinal lesions, suggesting that they may have caused previously unexplained gastrointestinal hemorrhage in dialysis patients. It was also suggested that the frequent use of PPI may be a cause of small intestinal lesions.

Effect of egualen sodium hydrate on small-intestinal mucosal damage induced by low-dose aspirin: a prospective randomized clinical trial.

Low-dose aspirin, which is widely used to reduce the risk of cardio- and cerebrovascular thrombosis, often induces gastroenteropathy by increasing the permeability of the mucosa. However, therapeutic strategies for patients with low-dose aspirin-induced small intestinal injury have not been determined. We evaluated the preventative effect of egualen sodium hydrate, a gastro-protective agent that suppresses indomethacin-induced small-intestinal damage in rats, against small-intestinal mucosal damage induced by low-dose aspirin in healthy adult male volunteers. Participants were randomly allocated to receive aspirin 100 mg/kg daily (control group, n = 10) or aspirin 100 mg/kg plus egualen sodium 30 mg daily (egualen sodium group, n = 10). Small intestinal mucosal injury was evaluated by capsule endoscopy two weeks after initiation of drug administration. Fecal analyses (occult blood test, immunochemical test, transferrin measurement and calprotectin measurement) were carried out before and after treatment. Egualen sodium significantly suppressed the total number of small intestinal injuries detected by capsule endoscopy and the positive ratio for the fecal occult blood test. Daily use of 30 mg of egualen sodium showed a preventative effect on low-dose aspirin-induced small intestinal injury. Since acid suppression therapy was reported to exacerbate NSAIDs-induced enteropathy via dysbiosis, egualen sodium may be useful for patients treated with low-dose aspirin.

Therapy of gastroesophageal reflux disease and functional dyspepsia overlaps with symptoms after usual-dose proton pump inhibitor: Acotiamide plus usual-dose proton pump inhibitor versus double-dose proton pump inhibitor.

BACKGROUND AND AIM: Gastroesophageal reflux disease (GERD) and functional dyspepsia (FD) often coexist or overlap. In this study, the efficacy of acotiamide in combination with a standard dose of rabeprazole for GERD and FD was compared with that of a double dose of rabeprazole. METHODS: Patients with overlap between GERD and FD experiencing heartburn and epigastric fullness symptoms after standard-dose proton pump inhibitor (PPI) for ≥ 8 weeks were randomized into two groups and received either acotiamide 300 mg/day + rabeprazole 10 mg/day or rabeprazole 20 mg/day for 4 weeks. Efficacy was assessed by reductions in symptom scores using the Izumo scale questionnaire and modified F-scale questionnaire. RESULTS: As the primary endpoint, three upper gastrointestinal symptoms (heartburn, epigastralgia, and epigastric fullness) were reduced by ≥ 50% in 40.8% and 46.9% of patients in the combination and PPI double-dose groups, respectively, with no significant difference between the two groups. Essentially similar results were obtained for the modified F-scale questionnaire. No serious adverse events were noted. CONCLUSIONS: Acotiamide 300 mg/day in combination with rabeprazole 10 mg/day or rabeprazole 20 mg/day relieved symptoms in patients with overlap between GERD and FD experiencing heartburn and epigastric fullness symptoms after standard-dose PPI for ≥ 8 weeks, and the efficacies did not differ between the two treatments. The combination therapy may be an alternative option for persistent symptoms in these patients.

A case of adenocarcinoma developed in the small intestine with chronic strongyloidiasis.

We experienced a case of intestinal strongyloidiasis complicated by jejunal carcinoma. A Japanese male in his 50s, who has a 7-year medical history of duodenal ulcers, complained of loss of appetite, nausea, vomiting and diarrhea. Computed tomography and gastroduodenal endoscopic examination revealed a stenosis of the duodenum. To remove the stenosis, gastric bypass surgery was performed. The pathological diagnosis of the resected jejunum was strongyloidiasis and well-differentiated adenocarcinoma with subserosal invasion and vascular infiltration. After administration of Ivermectin, Strongyloides stercoralis was not found in any biopsies or in the specimens of the intestine, which were resected due to cancer recurrence 2 years later. There are three possibilities for the reason of coexistence of S. stercoralis and adenocarcinoma: S. stercoralis caused the adenocarcinoma, S. stercoralis moved to the carcinoma, or just coincidence. Although it is difficult to prove a causal relationship between S. stercoralis and adenocarcinoma, this is the first report of adenocarcinoma developed in the jejunum with chronic strongyloidiasis. The number of nematode infections, including strongyloidiasis, is decreasing in Japan, although not worldwide. Therefore, it should be considered in patients with prolonged intestinal ulcers.

Determination of the adequate dosage of rebamipide, a gastric mucoprotective drug, to prevent low-dose aspirin-induced gastrointestinal mucosal injury.

Small intestinal mucosal injury caused by low-dose aspirin is a common cause of obscure gastrointestinal bleeding. We aimed to investigate the protective effects and optimal dose of rebamipide for low-dose aspirin-induced gastrointestinal mucosal injury. In this prospective randomized trial, 45 healthy volunteers (aged 20-65 years) were included and divided into three groups. The groups received enteric-coated aspirin 100 mg (low-dose aspirin) plus omeprazole 10 mg (Group A: proton pump inhibitor group), low-dose aspirin plus rebamipide 300 mg (Group B: standard-dose group), or low-dose aspirin plus rebamipide 900 mg (Group C: high-dose group). Esophagogastroduodenoscopy and video capsule endoscopy were performed, and the fecal occult blood reaction and fecal calprotectin levels were measured before and two weeks after drug administration. Although the fecal calprotectin levels increased significantly in Group A, they did not increase in Groups B and C. The esophagogastroduodenoscopic and video capsule endoscopic findings and the fecal occult blood test findings did not differ significantly among the three groups. In conclusion, standard-dose rebamipide is sufficient for preventing mucosal injury of the small intestine induced by low-dose aspirin, indicating that high-dose rebamipide is not necessary.

Blue mode imaging may improve the detection and visualization of small-bowel lesions: A capsule endoscopy study.

BACKGROUND/AIMS: Diagnostic miss rate and time consumption are the two challenging limitations of small-bowel capsule endoscopy (SBCE). In this study, we aimed to know whether using of the blue mode (BM) combined with QuickView (QV) at a high reviewing speed could influence SBCE interpretation and accuracy. MATERIALS AND METHODS: Seventy CE procedures were totally reviewed in four different ways; (1) using the conventional white light, (2) using the BM, [on a viewing speed at 10 frames per second (fps)], (3) using white light, and (4) using the BM (on a viewing speed at 20 fps). In study A, the results of (1) were compared with those of (2), and in study B, the results of (3) and (4) were separately compared with those of (1). RESULTS: In study A, the total number of the vascular (P < 0.001) and the inflammatory lesions (P = 0.005) detected by BM was significantly higher than that detected by the white light. No lesion was found using the white light that was not detected by the BM. Moreover, the BM highly improved the image quality of all the vascular lesions and the erythematous ones from the nonvascular lesions. In study B, the total number of only the vascular lesions, detected by the BM on a rapid speed of viewing at 20 fps was significantly higher than that detected by the white light (P = 0.035). However, the true miss rate for the BM was 4%. CONCLUSION: BM imaging is a new method that improved the detection and visualization of the vascular and erythematous nonvascular lesions of SB as compared with the conventional white light imaging. Using of the BM at a slow viewing speed, markedly reduced the diagnostic miss rate of CE.

What Kind of Capsule Endoscope Is Suitable for a Controllable Self-Propelling Capsule Endoscope? Experimental Study Using a Porcine Stomach Model for Clinical Application (with Videos).

BACKGROUND: We have been developing the Self-Propelling Capsule Endoscope (SPCE) that allows for controllability from outside of the body and real-time observation. What kind of capsule endoscope (CE) is suitable for a controllable SPCE is unclear and a very critical point for clinical application. We compared observing ability of three kinds of SPCEs with different viewing angles and frame rates. METHODS: Eleven buttons were sewed in an excised porcine stomach. Four examiners controlled the SPCE using PillCamSB2, -ESO2, and -COLON2 (Given Imaging Ltd., Israel), for 10 minutes each with the aim of detecting as many buttons and examining them as closely as possible. The ability to find lesions was assessed based on the number of detected buttons. The SPCE-performance score (SPS) was used to evaluate the ability to examine the lesions in detail. RESULTS: The SPCE-ESO2, -COLON2, and -SB2 detected 11 [interquartile range (IQR): 0], 10.5 (IQR, 0.5), and 8 (IQR, 1.0) buttons, respectively. The SPCE-ESO2 and -COLON2 had a significantly better ability to detect lesions than the -SB2 (p < 0.05). The SPCE-ESO2, -COLON2, and -SB2 had significantly different SPS values of 22 (IQR, 0), 16.5 (IQR, 1.5), and 14 (IQR, 1.0), respectively (p < 0.05 for all comparisons; SPCE-SB2 vs. -ESO2, -SB2 vs. -COLON2, and -ESO2 vs. -COLON2). CONCLUSIONS: PillCamESO2 is most suitable in different three CEs for SPCE for examining lesions in detail of the stomach.

Current Topics of Strategy of NSAID-Induced Small Intestinal Lesions.

Small intestinal mucosal injuries have been recently recognized as common complications associated with non-steroidal anti-inflammatory drugs (NSAIDs) because video capsule endoscopy and balloon enteroscopy are now available for the detection of small intestinal lesions. Small intestinal injury occurs not in an acid-dependent mechanism but by various factors such as enteric bacteria, bile acids, prostaglandin (PG) deficiency and topical factors (abnormal intestinal mucosal permeability, mitochondrial dysfunction, reactive oxygen species, endoplasmic reticulum stress and so on), and there is no well-established prophylactic approach. Several experimental and clinical studies found the effectiveness of some of the mucoprotective drugs, PG analogs, but not that of acid suppressants. Considering the effect of proton pump inhibitors (PPIs) for upper gastrointestinal (GI) disease and in the small intestine, the following 2 kinds of strategies against NSAID-induced GI injuries may be recommended. In patients with a high risk of upper GI disease (peptic ulcer etc.), simultaneous administration of a PPI (for upper GI disease) and a mucoprotective drug (for small intestine) is needed to prevent NSAID-induced GI injury. In other cases, an effective mucoprotective drug is enough for the protection of the entire digestive tract, that is, starting from the esophagus to the small intestine. These strategies may fulfill both economical and curative effects.

Effect of long-term proton pump inhibitor therapy and healing effect of irsogladine on nonsteroidal anti-inflammatory drug-induced small-intestinal lesions in healthy volunteers.

This study assessed time-course changes of the small intestinal lesions during long-term treatment with diclofenac sodium plus omeprazole and the effects of irsogladine on such lesions. Thirty two healthy volunteers were treated with diclofenac sodium (75 mg/day) plus omeprazole (10 mg/day) for 6 weeks, with irsogladine (4 mg/day) added from weeks 6 to 10 (Group A) or with diclofenac sodium plus irsogladine for 6 weeks (Group B). Five volunteers received diclofenac sodium plus omeprazole for 10 weeks (Group C). Subjects underwent capsule endoscopy at each time. In Group A, the number of lesions remarkably increased at week 2, but the worse was not found at week 6 compared with week 2, whereas no exacerbation of lesions was observed in Group B. Additional treatment with irsogladine from weeks 6 to 10 in Group A significantly decreased the number of lesions at weeks 10 compared with Group C. In Group C, no significant change in lesions was observed since weeks 2. In conclusions, a PPI did not prevent the occurrence of small intestinal damage. However such lesions were not aggravated since weeks 2. These suggested mucosal adaptation may occur in the small intestine. Irsogladine was effective in both preventing and healing such lesions.

Evaluation of the clinical efficacy of colon capsule endoscopy in the detection of lesions of the colon: prospective, multicenter, open study.

BACKGROUND: Colon capsule endoscopy (CCE) is a new procedure for colon imaging. Limited information is available regarding visualization of flat colon lesions and patient acceptability in Japan. OBJECTIVE: The aims of this study were to evaluate the sensitivity of CCE in detecting polyps and other lesions compared with optical colonoscopy (OC) and to evaluate its safety and acceptability in a cohort of Japanese patients. DESIGN: A prospective, open-label, clinical study in Japan. SETTING: Multicenter. PATIENTS: Patients referred for OC because of personal history of polyps ≥6 mm or any other colon lesion that required endoscopic or surgical treatment. INTERVENTIONS: CCE followed by therapeutic colonoscopy. MAIN OUTCOME MEASUREMENTS: The primary endpoint was per-patient sensitivity of CCE in detecting significant colon lesion. The secondary endpoints were CCE safety and patient acceptability. RESULTS: Sixty-six of the 72 patients enrolled in the study were evaluated for efficacy. The per-patient sensitivity was 94% (95% confidence interval [CI], 88.2%-99.7%). The per-polyp sensitivity was 86.6% (95% CI, 81.3%-91.9%) when pathology-confirmed polyps were considered true positives. There were no adverse events related to CCE, and the acceptability of CCE was high. LIMITATIONS: All patients had previously confirmed colon lesions, which may have falsely elevated the sensitivity of CCE. CONCLUSION: CCE had a high sensitivity for detecting significant colon lesions. CCE was safe and had a high level of patient acceptability. ( CLINICAL TRIAL REGISTRATION NUMBER: University Hospital Medical Information Network, UMIN000007258.).

The effects of a TGR5 agonist and a dipeptidyl peptidase IV inhibitor on dextran sulfate sodium-induced colitis in mice.

BACKGROUND AND AIM: Luminal nutrients stimulate enteroendocrine L cells to release gut hormones, including intestinotrophic glucagon-like peptide-2 (GLP-2). Because L cells express the bile acid receptor TGR5 and dipeptidyl peptidase-IV (DPPIV) rapidly degrades GLPs, we hypothesized that luminal TGR5 activation may attenuate intestinal injury via GLP-2 release, which is enhanced by DPPIV inhibition. METHODS: Intestinal injury was induced in mice by administration of dextran sulfate sodium (DSS) in drinking water (free access to water containing 5% DSS for 7 days). The selective TGR5 agonist betulinic acid (BTA) and the DPPIV inhibitor sitagliptin phosphate monohydrate (STG) were administered orally for 7 days. Male C57BL/6 mice (6-7 weeks old) were divided into five groups: normal control group, disease control group, BTA low group (drinking water containing 15 mg/L BTA), BTA high group (50 mg/L BTA), and BTA high + STG (3 mg/kg, i.g.) group. RESULTS: The selective TGR5 agonist BTA dose-dependently suppressed disease activity index and mRNA expression of the pro-inflammatory cytokines interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α in the colon. Nevertheless, STG administration had little additive effect on BTA-induced protection. Fibroblast activation protein mRNA expression, but not expression of other DPP family members, was increased in the colon of DSS-treated mice with increased mucosal DPPIV. Co-administration of the selective GLP-2 antagonist GLP-2 (3-33) reversed the effect of BTA. CONCLUSION: The selective TGR5 agonist BTA ameliorated DSS-induced colitis in mice via the GLP-2 pathway with no effect of DPPIV inhibition, suggesting that other DPP enzymatic activity is involved in GLP-2 degradation.

Geranylgeranylacetone, a gastromucoprotective drug, protects against NSAID-induced esophageal, gastroduodenal and small intestinal mucosal injury in healthy subjects: A prospective randomized study involving a comparison with famotidine.

OBJECTIVE: A treatment strategy to inhibit nonsteroidal anti-inflammatory drug (NSAID)-induced small intestinal lesions has not yet been established. To clarify whether monotherapy with a gastromucoprotective drug, geranylgeranylacetone (GGA), inhibits NSAID-induced acute mucosal injury of the upper digestive tract and small intestine. METHODS: A prospective, randomized, comparative study. All procedures were performed at Osaka Medical College. The subjects, thirty healthy adult volunteers, were randomly divided into two groups. In the NSAID-GGA group, 75 mg/day of diclofenac sodium and 150 mg/day of GGA were orally administered for two weeks. In the NSAID-FAM group, 75 mg/day of diclofenac sodium and 20 mg/day of famotidine (FAM) were orally administered for two weeks. esophagogastroduodenoscopy (EGD) and video capsule endoscopy (VCE) were performed before and two weeks after drug administration. In addition, we measured fecal occult blood reactions and the fecal calprotectin levels. RESULTS: No significant differences were observed between the groups in the mean increase in esophageal/gastroduodenal lesions. The mean increases in the scores in the NSAID-FAM group (NSAID-GGA group) of small bowel lesions were as follows: erythema: 1.93 ± 0.67 (0.30 ± 0.60), erosions: 1.13 ± 0.54 (0.38 ± 0.35), ulcers: 0.73 ± 0.33 (0.07 ± 0.07) and edema: 0.53 ± 0.44 (0.07 ± 0.07). The scores for erythema and ulcers were significantly lower in the NSAID-GGA group than in the NSAID-FAM group (p=0.032 and 0.0165, respectively). CONCLUSION: We compared the prophylactic effects of a mucoprotective drug, GGA, and an H2RA, famotidine, on mucosal injury involving the esophagus to the small intestine related to the two-week oral administration of diclofenac sodium in healthy volunteers. In the upper digestive tract, the prophylactic effects were similar between the two drugs. However, in the small intestine, GGA more markedly inhibited the development of lesions compared to famotidine.

Preventive effect of irsogladine or omeprazole on non-steroidal anti-inflammatory drug-induced esophagitis, peptic ulcers, and small intestinal lesions in humans, a prospective randomized controlled study.

BACKGROUND: Proton-pump inhibitors such as omeprazole are a standard treatment to prevent non-steroidal anti-inflammatory drug-induced upper gastrointestinal mucosal injuries. However, it is unclear which drugs may protect against all NSAID-induced digestive-tract injuries. Here, we compare the efficacy of the gastromucoprotective drug irsogladine with omeprazole in preventing NSAID-induced esophagitis, peptic ulcers, and small-intestinal mucosal injury in healthy subjects. METHODS: Thirty-two healthy volunteers were assigned to an irsogladine group (Group I; n = 16) receiving diclofenac sodium 75 mg and irsogladine 4 mg daily for 14 days, or an omeprazole group (Group O; n = 16) receiving diclofenac sodium 75 mg and omeprazole 10 mg daily for 14 days. Esophagitis and peptic ulcers were evaluated by esophagogastroduodenoscopy and small-intestinal injuries by capsule endoscopy, fecal calprotectin, and fecal occult blood before and after treatment. RESULTS: There was no significant difference between Group I and Group O with respect to the change in lesion score in the esophagus, stomach, and duodenum before and after treatment.NSAID treatment significantly increased the number of small intestinal mucosal breaks per subject by capsule endoscopic evaluation, from a basal level of 0.1 ± 0.3 up to 1.9 ± 2.0 lesions in Group O (p = 0.0002). In contrast, there were no significant changes in the mean number of mucosal breaks before and after co-treatment in Group I (0.3 ± 0.8 to 0.5 ± 0.7, p = 0.62), and the between-group difference was significant (p = 0.0040). Fecal calprotectin concentration, when the concentration before treatment was defined as 1, was significantly increased both in Group O (from 1.0 ± 0.0 to 18.1 ± 37.1, p = 0.0002) and Group I (from 1.0 ± 0.0 to 6.0 ± 11.1, p = 0.0280); the degree of increase in Group O was significantly higher compared with that in Group I (p<0.05). In addition, fecal occult blood levels increased significantly in Group O (p = 0.0018), but there was no change in Group I (p = 1.0), and the between-group difference was significant (p = 0.0031). CONCLUSION: Irsogladine protected against NSAID-induced mucosal injuries throughout the gastrointestinal tract, from esophagus to small intestine, significantly better than omeprazole. TRIAL REGISTRATION: This study was registered in the UMIN Clinical Trials Registry (Registry ID number; UMIN000008114).

Clinical effects of adalimumab treatment with concomitant azathioprine in Japanese Crohn's disease patients.

AIM: To assess adalimumab's efficacy with concomitant azathioprine (AZA) for induction and maintenance of clinical remission in Japanese Crohn's disease (CD) patients. METHODS: This retrospective, observational, single-center study enrolled 28 consecutive CD patients treated with adalimumab (ADA). Mean age and mean disease duration were 38.1 ± 11.8 years and 11.8 ± 10.1 years, respectively. The baseline mean Crohn's disease activity index (CDAI) and C-reactive protein were 177.8 ± 82.0 and 0.70 ± 0.83 mg/dL, respectively. Twelve of these patients also received a concomitant stable dose of AZA. ADA was subcutaneously administered: 160 mg at week 0, 80 mg at week 2, followed by 40 mg every other week. Clinical response and remission rates were assessed via CDAI and C-reactive protein for 24 wk. RESULTS: The mean CDAI at weeks 2, 4, 8, and 24 was 124.4, 120.2, 123.6, and 135.1, respectively. The CDAI was significantly decreased at weeks 2 and 4 with ADA and was significantly suppressed at 24 wk with ADA/AZA. Overall clinical remission rates at weeks 4 and 24 were 66.7% and 63.2%, respectively. Although no statistically significant difference in C-reactive protein was demonstrated, ADA with AZA resulted in a greater statistically significant improvement in CDAI at 24 wk, compared to ADA alone. CONCLUSION: Scheduled ADA with concomitant AZA may be more effective for clinical remission achievement at 24 wk in Japanese Crohn's disease patients.

Endoscopic and histopathological evaluation of collagenous colitis.

Collagenous colitis (CC) is a well-known cause of chronic non-bloody diarrhea, especially in elderly women. CC is characterized histopathologically by an increase in the thickness of the subepithelial collagen layer to at least 10 µm, epithelial damage, and chronic inflammation of the lamina propria. Generally, the colonic mucosa in CC is macroscopically normal, although minor, non-specific abnormalities may be found. Due to the recent advancement of endoscopic and diagnostic technologies, however, microscopic mucosal abnormalities and specific longitudinal linear lacerations of the mucosa characteristic of CC have been identified. The association of CC with non-steroidal anti-inflammatory drugs and proton pump inhibitors has also been reported. Since definitive diagnosis of CC has to rely on pathologically documented collagen bands and mononuclear infiltration, the efficiency and precision of colonic biopsy need to be improved. Of the 29 CC patients that we have encountered at our institution, it was in 15 of 29 cases that the endoscopic finding that we performed a biopsy on was apparent. Our comparison of the endoscopic and histopathological findings of CC in the 15 patients showed that the mucosa frequently appeared coarse and nodular on the surface of the mucosa, which was also significantly thicker in collagen bands, demonstrating a strong correlation between collagen band formation and CC. Also, the coarse and nodular surface of the mucosa was most frequently seen affecting the proximal colon. The results suggest that endoscopic observation and biopsy of the proximal colon, where a coarse and nodular surface of the mucosa is often found, may be useful for confirmation of the diagnosis in patients with suspected CC.

Simvastatin attenuates intestinal fibrosis independent of the anti-inflammatory effect by promoting fibroblast/myofibroblast apoptosis in the regeneration/healing process from TNBS-induced colitis.

BACKGROUND: Intestinal deformity and stenosis are induced by fibrosis during the process healing of intestinal chronic inflammation in inflammatory bowel disease (IBD). Potent anti-inflammatory treatment of patients with Crohn's disease (CD) may induce fibrous stenosis, and this is often difficult to treat in clinical practice. Therefore, it is necessary to develop a treatment strategy that concomitantly exhibits repair/regenerative and anti-fibrotic effects, in addition to the current anti-inflammatory effect, for the treatment of inflammatory bowel diseases. However, the relationship between the course of inflammatory activity and the healing process and fibrogenesis has not been elucidated; although the complex involvement of various factors in the mechanism of biological fibrosis has been investigated. Simvastatin (SIMV), an HMG-CoA reductase inhibitor, exhibits anti-inflammatory and anti-fibrotic effects. The current study established a model of the regeneration/healing process from TNBS-induced colitis and investigated the anti-inflammatory and anti-fibrotic effects of SIMV. SUBJECTS AND METHODS: Four groups of TNBS-induced colitis model were prepared using male SJL/J mice: A: Normal control group, B: control group, and C and D: treatment groups. The mucosal healing process was classified into three phases (an early phase: inflammation period, a mid-phase: regeneration promoting period, and a late phase: regeneration-converging period), and inflammation, the expression of fibrosis-related growth factors, and induction of apoptosis of fibrosis-related cells were compared in each period. RESULTS: (1) The clinical findings showed that SIMV showed anti-inflammatory effects with body weight gain and improvement of epithelial injury in the late phase. Histological (macroscopic/microscopic) improvement was noted in the mid- and late phases. The inflammatory cytokine (TNF-α) level significantly decreased in the mid- and late phases in the high-dose treatment group. (2) SIMV also had anti-fibrotic effects characterized by a dose-dependent decrease in the level of a fibrosis-related growth factor (CTGF) in the early and mid-phases, irrespective of inflammation or changes in the TGF-ß(1) level. Dose-dependent induction of apoptosis was noted in both fibroblasts and myofibroblasts from a relatively early stage. CONCLUSIONS: The results suggested that SIMV induces anti-fibrotic activity that is not directly involved in the anti-inflammatory effect from a relatively early stage the healing process of TNBS-induced colitis.

R-etodolac induces E-cadherin and suppresses colitis-related mouse colon tumorigenesis.

Colorectal cancer is one of the most serious complications of ulcerative colitis (UC), and the risk of UC-associated neoplasia increases as the region and duration of the disease increase. Selective cyclooxygenase (COX)-2 inhibitors effectively diminish carcinogenesis in a murine UC model. However, this may exacerbate colitis. The selective COX-2 inhibitor etodolac is marketed as a racemic mixture of the R- and S-enantiomers. The biochemical and pharmacological effects of etodolac are caused by the S-enantiomer, while the R-enantiomer lacks COX-inhibitory activity. In this study, we evaluated the effect of R-etodolac on colitis-related mouse colon tumorigenesis. The mice received 1,2-dimethlhydrazine (DMH), and then chronic colitis was induced by administration of two cycles of DSS (each cycle: 3% DSS for 7 days followed by distilled water for 14 days). The mice were sacrificed 28 days after the completion of both cycles. Mice were divided into the following groups: group A served as a disease control; group B received a low (2-mg/kg) dose of R-etodolac every 3 days during the entire period; group C received a high (10-mg/kg) dose of R-etodolac on the same schedule as group B; and group D served as a normal control. Administration of R-etodolac decreased the disease activity index during the DSS administration cycle. The mean number of tumors was 17.8, 15.2, 6.0, and 0 in groups A-D, respectively. In group C, R-etodolac significantly suppressed the occurrence of neoplasia (p<0.05). Although R-etodolac treatment did not affect COX-2 expression, it significantly enhanced expression of E-cadherin in both neoplastic lesions and background mucosa (i.e., lesion-free colon). Thus, administration of R-etodolac exerts a suppressive effect on the development of neoplasia in a murine model of DSS-induced colitis without exacerbation of the colitis. These results suggest that R-etodolac could be useful in the prevention of UC-associated neoplasia.

In vivo trial of a driving system for a self-propelling capsule endoscope using a magnetic field (with video).

BACKGROUND: A capsule endoscope does not allow the examiner to observe a lesion from the desired direction in real time. OBJECTIVE: To develop a driving system for a self-propelling capsule endoscope (SPCE) by using a magnetic field. SETTING: Experimental endoscopic study in a live dog model. DESIGN AND INTERVENTIONS: A microactuator was developed with the aim of remote-control operation. We developed a driving system for SPCE by attaching a capsule endoscope to this medical microactuator and performed the following experiments. (1) We operated this SPCE by remote control in the stomach of a dog under sedation and obtained endoscopic images using a real-time monitoring system only. (2) We placed a hemostatic clip on the gastric mucosa and recorded images of this clip with the SPCE. (3) We also placed clips at 2 other sites in the stomach and asked the SPCE operator, who was unaware of the location of the clips, to identify the site, number, and color of the clips. MAIN OUTCOME MEASUREMENTS: Evaluation of performance of a driving system for SPCE. RESULTS: The operator was able to obtain endoscopic images with the SPCE in the stomach of a dog in vivo, in any desired direction, by remote control. SPCE produced clear images of the clips placed in the stomach. The operator was able to easily identify the site, number, and color of the clips. LIMITATIONS: Animal model. CONCLUSIONS: Our trial suggests the possibility of clinical application of the driving system for an SPCE using a magnetic field.