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.

Role of small intestinal bacterial overgrowth in severe small intestinal damage in chronic non-steroidal anti-inflammatory drug users.

OBJECTIVE. Enteric bacteria play a significant role in the pathogenesis of non-steroidal anti-inflammatory drug (NSAID)-induced small intestinal damage. However, the association between small intestinal bacterial overgrowth (SIBO) and NSAID-induced small intestinal damage remains unclear. The aim of the study was to examine the association between SIBO and the presence of NSAID-induced severe small intestinal damage or its symptoms in chronic NSAID users. MATERIALS AND METHODS. Forty-three patients who had been using NSAIDs for over 3 months were enrolled. They were examined by capsule endoscopy and a lactulose hydrogen breath test (LHBT). We defined severe small intestinal damage as the presence of more than four small erosions or large erosions/ulcers. The LHBT result was considered positive if there was an increase in the level of breath hydrogen gas of >20 ppm above baseline. RESULTS. Out of 43 patients, 22 (51%) had severe small intestinal damage. The LHBT was positive in 5 of 21 patients (24%) without severe small intestinal damage and in 13 of 21 patients (59%) with severe small intestinal damage. Multiple logistic regression analysis showed that an LHBT-positive result was significantly associated with increased odds ratio for severe small intestinal damage (OR, 6.54; 95% CI, 1.40-30.50). There was no significant difference in the presence of symptoms between the LHBT-positive and LHBT-negative patients with severe small intestinal damage. CONCLUSION. SIBO might have a role in the development of severe small intestinal damage in chronic NSAID users.

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.

Endoscopic radial incision and cutting method for refractory esophageal stricture after endoscopic submucosal dissection of superficial esophageal carcinoma.

A 59-year-old woman and a 69-year-old man had esophageal strictures that were refractory to over 10 therapeutic attempts with endoscopic balloon dilation (EBD) after endoscopic submucosal dissections (ESD) for superficial esophageal carcinoma (SEC). The strictured lesions in both patients improved remarkably with a new endoscopic modality (endoscopic radial incision and cutting [ERIC]), which was carried out one to three times, and stricture recurrence was not noted throughout the follow-up period. ERIC is a safe and efficient method for treating refractory strictures after EBD caused by ESD for SEC.

Internal hypoechoic feature by EUS as a possible predictive marker for the enlargement potential of gastric GI stromal tumors.

BACKGROUND: There is no clinical predictor for the enlargement potential of gastric GI stromal tumors (GISTs) during the follow-up observation period. OBJECTIVE: The aim of our study was to identify predictive markers for the enlargement potential of gastric GISTs on the basis of various endosonographic features determined at the initial examination. DESIGN: Single-center retrospective analysis. SETTING: Academic university hospital in Japan. PATIENTS: All patients (n = 74) with histologically diagnosed GISTs in the stomach underwent EUS. INTERVENTION: EUS. MAIN OUTCOME MEASUREMENTS: We analyzed the following endoscopic and EUS features: mucosal ulceration, irregular shape, irregular border, heterogeneity, internal hyperechoic spot, hypoechoic area, and anechoic area of gastric GISTs in 3 groups according to tumor size. Furthermore, we compared the characteristics between increased growth and unchanged growth of GISTs, that were defined on the basis of the novel tumor growth index: changes in tumor volume/follow-up interval (days between initial EUS and second EUS) (mm(3)/day). RESULTS: The presence of heterogeneity (P = .016) and anechoic area (P = .003) was significantly highest in the group with the largest tumor size. The increased growth group had a higher presence of hypoechoic area than did the unchanged growth group (84.2% vs 51.9%, P = .023). Multivariate analysis showed that the presence of a hypoechoic area was an enlargement-associated factor (odds ratio 5.38; 95% confidence interval 1.19-24.39; P = .029). LIMITATIONS: Retrospective design of the study. CONCLUSIONS: The internal hypoechoic area determined by EUS may be a predictor for the enlargement potential of gastric GISTs.

Pathogenesis of proton-pump inhibitor-refractory non-erosive reflux disease according to multichannel intraluminal impedance-pH monitoring.

BACKGROUND AND AIM: Proton-pump inhibitor (PPI) therapy is the first-line treatment for gastroesophageal reflux disease; however, there are some reports of PPI failure in cases of non-erosive reflux disease (NERD). Among the pathogenic factors associated with PPI-refractory NERD, reflux other than acid reflux can not be detected by conventional pH monitoring. The purpose of this study was to clarify the usefulness of multichannel intraluminal impedance-pH (MII-pH) monitoring for PPI-refractory NERD patients and examine the pathogenesis. METHODS: We used MII-pH monitoring to examine 29 PPI-refractory NERD patients on PPI treatment. Reflux parameters, symptom index (SI: positive if ≥ 50%), and proximal migration were analyzed. The acidity of the reflux was divided into acid (nadir pH ≤ 4) and non-acid (nadir pH > 4). Subjects were classified into reflux-related disease (abnormal reflux parameters or positive SI) and non-reflux-related disease (normal reflux parameters and negative SI). RESULTS: Of the 29 subjects, 21 were diagnosed with reflux-related disease, including 6 with acid reflux type and 15 with non-acid reflux type, and 8 were diagnosed with non-reflux-related disease. Of the total 1816 liquid reflux episodes, 834 showed proximal migration, which was more common in symptomatic reflux than in asymptomatic reflux. CONCLUSIONS: MII-pH monitoring could distinguish reflux-related disease (especially non-acid type) from PPI-refractory NERD. Proximal migration was associated with symptomatic reflux in PPI-refractory NERD patients.

High prevalence of gastroesophageal reflux symptoms in patients with non-alcoholic fatty liver disease associated with serum levels of triglyceride and cholesterol but not simple visceral obesity.

BACKGROUND/AIMS: Visceral obesity is commonly involved in the pathogenesis of gastroesophageal reflux disease (GERD) and non-alcoholic fatty liver disease (NAFLD). However, other characteristic factors different from visceral obesity are associated with the pathogenesis of NAFLD. We investigated the prevalence of GERD symptoms in patients with NAFLD and its associated risk factors. METHODS: NAFLD (n = 96) and controls (n = 139) were enrolled in this study. GERD symptoms were evaluated by using a frequency scale for the symptoms of GERD. RESULTS: GERD symptom score and its prevalence rate were higher in the NAFLD group (7.4 ± 0.7, 37%) than those seen in the control groups (4.5 ± 0.4, 20%), which was independent of sex, age, and body mass index (BMI). GERD symptoms were correlated with insulin resistance (r = 0.167, p = 0.011), total cholesterol (T-CHO) (r = 0.138, p = 0.034), triglyceride (TG) (r = 0.178, p = 0.006), or immunoreactive insulin (r = 0.173, p = 0.008) but not BMI (r = 0.089, p = 0.175). GERD symptoms of the NAFLD group were significantly severer in the higher group of T-CHO and TG levels than those in the lower group. Multivariate analysis proved that risk factors related to GERD symptoms were TG (OR 3.96, 95% CI 1.31-11.9) and T-CHO (OR 3.39, 95% CI 1.11-10.3). CONCLUSION: The severity and prevalence of GERD symptoms in patients with NAFLD were high, which was associated with serum levels of TG and T-CHO but not BMI.

Dysregulated upregulation of T-cell immunoglobulin and mucin domain-3 on mucosal T helper 1 cells in patients with Crohn's disease.

OBJECTIVE: T-cell immunoglobulin and mucin domain-3 (TIM-3) is a unique cell surface molecule expressed on T helper 1 (Th1) cells. Engagement of TIM-3 by ligand galectin-9 leads to dampened Th1 immunity. We investigated TIM-3 and galectin-9 expression in inflammatory bowel disease (IBD) patients and in healthy controls, and evaluated the immune role of the TIM-3 pathway in Crohn's disease (CD) pathogenesis. MATERIAL AND METHODS: We used flow cytometry to investigate TIM-3 expression on mononuclear cells isolated from the intestinal mucosa and peripheral blood cells of patients with IBD and healthy controls. We also evaluated galectin-9 mRNA expression on endoscopically obtained intestinal mucosal cells. RESULTS: TIM-3 was constitutively expressed on Th cells isolated from the intestinal mucosa of IBD patients and healthy controls. While we observed low TIM-3 expression on Th cells isolated from peripheral blood mononuclear cells (PBMCs), high TIM-3 expression was induced by Th1 stimulation. The level of TIM-3 expression on Th cells isolated from intestinal mucosa and stimulated PBMCs was significantly lower in CD patients than in healthy controls. CONCLUSIONS: Our data show that TIM-3 upregulation on Th1 cells is dysregulated in patients with CD. Low TIM-3 expression on Th1 cells may provide a clue toward resolution of the inflammation associated with chronic inflammatory disease. These findings should contribute to develop understanding of CD pathogenesis.

Gastrointestinal bleeding after percutaneous coronary intervention.

Percutaneous coronary intervention (PCI) is now performed in a wide range of patients with coronary artery disease. Complications of PCI include in-stent re-stenosis and in-stent thrombosis. According to the recent 2005 guidelines of the American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions, dual antiplatelet therapy with low-dose aspirin and thienopyridine derivatives such as ticlopidine and clopidogrel should be used in patients who have undergone PCI. A serious complication of dual antiplatelet therapy is bleeding, most of which arise from the gastrointestinal (GI) tract. In this article we review published studies about GI bleeding in patients who have undergone PCI. The prevalence of GI bleeding in patients who are administered dual antiplatelet therapy following PCI is approximately 2%, and GI bleeding after PCI is associated with increased morbidity, mortality, duration of hospitalization and cost. Advanced age, a history of peptic ulcer disease, co-administration of non-steroidal anti-inflammatory drugs, co-administration of anticoagulants, and physiological stress are considered to be the major risk factors for GI bleeding in patients undergoing antiplatelet therapy following PCI. Recent clinical and experimental studies indicate that administration of low-dose aspirin may also increase the risk of adverse events in the small intestine. Although some prophylactic strategies such as proton-pump inhibitor, H2 receptor antagonist and eradication of Helicobacter pylori are proposed, there are few randomized controlled trials assessing the best strategy for the prevention of GI bleeding after PCI. Further extensive studies are required to ascertain the beneficial effect of prophylactic agents for dual antiplatelet therapy following PCI.

Gastrointestinal endoscopic practice during COVID-19 pandemic: a multi-institutional survey.

Introduction. An on-going coronavirus disease 2019 (COVID-19) has become a challenge all over the world. Since an endoscopy unit and its staff are at potentially high risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we conducted a survey for the management of the gastrointestinal endoscopic practice, personal protective equipment (PPE), and risk assessment for COVID-19 during the pandemic at multiple facilities.Methods. The 11-item survey questionnaire was sent to representative respondent of Department of Gastroenterology, Osaka City University Hospital, and its 19 related facilities.Results. A total of 18 facilities submitted valid responses and a total of 373 health care professionals (HCPs) participated. All facilities (18/18: 100%) were screening patients at risk for SARS-CoV-2 infection before endoscopy. During the pandemic, we found that the total volume of endoscopic procedures decreased by 44%. Eleven facilities (11/18: 61%) followed recommendations of the Japan Gastroenterological Endoscopy Society (JGES); consequently, about 35%-50% of esophagogastroduodenoscopy and colonoscopy were canceled. Mask (surgical mask or N95 mask), face shield/goggle, gloves (one or two sets), and gown (with long or short sleeves) were being used by endoscopists, nurses, endoscopy technicians, and endoscope cleaning staff in all the facilities (18/18: 100%). SARS-CoV-2 infection risk assessment of HCPs was conducted daily in all the facilities (18/18: 100%), resulting in no subsequent SARS-CoV-2 infection in HCPs.Conclusion. COVID-19 has had a dramatic impact on the gastrointestinal endoscopic practice. The recommendations of the JGES were appropriate as preventive measures for the SARSCoV-2 infection in the endoscopy unit and its staff.

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

Prostaglandin (PG) E(2) 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 PGE(2), 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.

Leptin promotes gastric ulcer healing via upregulation of vascular endothelial growth factor.

BACKGROUND AND AIM: Leptin, a key hormone in regulation of food intake and energy expenditure, exerts pleiotropic cytokine-like biological effects. Its role in gastric ulcer healing is unclear. In this study, we investigated the role of leptin in gastric ulcer healing. METHODS: Experimental gastric ulcer was induced by focal serosal application of acetic acid in leptin-deficient ob/ob mice and wild-type mice. Healing of gastric ulcer and angiogenesis in the ulcer tissue was evaluated. RESULTS: Gastric ulcer healing was delayed in ob/ob mice compared with that in wild-type mice. The impairment of ulcer healing observed in ob/ob mice was characterized by reduced expression of vascular endothelial growth factor (VEGF) and impairment of angiogenesis. Systemic administration of leptin to ob/ob mice reversed the impairment of gastric ulcer healing; this reversal was accompanied by an increase in VEGF expression and angiogenesis. Although mRNA for leptin was not expressed in normal gastric mucosa and not induced in ulcerous tissue, leptin receptor expression was markedly upregulated in gastric epithelial cells at ulcer margins, and was colocalized with VEGF. CONCLUSION: These findings suggest that leptin promotes gastric ulcer healing by induction of angiogenesis in the granular tissue of ulcers via upregulation of VEGF expression.

[Gastric ulcer in the elderly: general concept and clinical features].

The total number of elderly persons with gastric ulcers in Japan is increasing with an improvement in the average life expectancy. So far, gastric ulcer in elderly persons is considered proximal gastric ulcer due to corpus-predominant atrophic gastritis. However, the clinical features of the disease will change with a decrease in the number of persons with Helicobacter pylori infection. On the other hand, the numbers of persons with gastric ulcers associated with aging-related diseases and those with gastric ulcers induced by drugs such as nonsteroidal anti-inflammatory drugs and aspirin are increasing. Even recently, there have been no changes in the mortality of patients with severe gastric ulcers. Management based on pathological conditions of gastric ulcers in the elderly persons is required.

Probiotic Lactobacillus casei strain Shirota prevents indomethacin-induced small intestinal injury: involvement of lactic acid.

Inflammatory responses triggered by activation of the lipopolysaccharide (LPS)/Toll-like receptor (TLR) 4 signaling pathway are a key mechanism in nonsteroidal anti-inflammatory drug-induced enteropathy. The aim of this study was to investigate the probiotic effect of Lactobacillus casei strain Shirota (LcS) on indomethacin-induced small intestinal injury. Rats pretreated with viable LcS or heat-killed LcS once or once daily for a week were administered indomethacin by gavage to induce injury. Anti-inflammatory effects of L-lactic acid (1-15 mM) were evaluated in vitro by use of THP-1 cells. One-week treatment with viable LcS prevented indomethacin-induced intestinal injury with increase in the concentration of lactic acid in small intestinal content and inhibited increases in myeloperoxidase activity and expression of mRNA for tumor necrosis factor-alpha (TNF-alpha) while affecting neither TLR4 expression nor the number of gram-negative bacteria in intestinal content, whereas neither heat-killed LcS nor a single dose of viable LcS inhibited intestinal injury. Prevention of this injury was also observed in rats given l-lactic acid in drinking water. Both L-lactic acid and LcS culture supernatant containing 10 mM lactic acid inhibited NF-kappaB activation and increases in TNF-alpha mRNA expression and TNF-alpha protein secretion in THP-1 cells treated with LPS. Western blot analyses showed that both L-lactic acid and LcS culture supernatants suppressed phosphorylation and degradation of I-kappaB-alpha induced by LPS without affecting expression of TLR4. These findings suggest that LcS exhibits a prophylactic effect on indomethacin-induced enteropathy by suppressing the LPS/TLR4 signaling pathway and that this probiotic effect of LcS may be mediated by L-lactic acid.

Anti-inflammatory effects of IL-17A on Helicobacter pylori-induced gastritis.

Helicobacter pylori-induced immune responses are skewed toward a T helper (Th) 1 phenotype. IL-17-producing Th17 cells have recently been discovered, and we examined the role of IL-17A in H. pylori-induced gastritis. Six months after inoculation with H. pylori, the mice received an intraperitoneal injection of recombinant IL-17A, anti-IL-17A antibody or irrelevant IgG(2a) for 3days. H. pylori infection markedly increased mRNA for IL-17A. Double immunofluorescence studies showed that IL-17A proteins were expressed on CD4(+) T cells, macrophages, and dendritic cells. H. pylori infection elevated mRNAs for IL-12, IFN-gamma, and TNF-alpha with increase in myeloperoxidase activity, whereas it did not affect mRNAs for IL-4 and IL-5. Neutralization of IL-17A elevated mRNAs for IFN-gamma and TNF-alpha, and myeloperoxidase activity, whereas recombinant IL-17A had a tendency to reduce these parameters. In conclusion, IL-17A exerts anti-inflammatory effects on H. pylori-induced gastritis through suppression of Th1 differentiation.

Predictive factors of worsening of esophageal varices after balloon-occluded retrograde transvenous obliteration in patients with gastric varices.

OBJECTIVES: Although balloon-occluded retrograde transvenous obliteration (B-RTO) is useful for management of gastric varices, worsening of esophageal varices (EV) is the most important complication of B-RTO. The predictive factors of worsening of EV have not been evaluated in detail. This study was designed to evaluate the role of endoscopic color Doppler ultrasonography (ECDUS) in the detection of possible risk factors for worsening of EV after B-RTO. METHODS: A total of 39 cirrhotic patients with high-risk gastric varices successfully treated by B-RTO were included in this study. All patients underwent ECDUS before B-RTO to measure hemodynamic parameters of gastric varices and regular endoscopic follow-up after B-RTO to detect worsening of EV. The risk factors were analyzed by Cox's proportional hazards regression. RESULTS: Worsening of EV was found in 24 (61.5%) patients. The presence of esophageal varices before B-RTO and a lower degree of liver dysfunction (Child-Pugh class B) were statistically independent risk factors for worsening of EV after B-RTO (hazard ratio, HR, 5.81, 95% confidence interval, CI, 1.71-19.77 and HR 2.92, 95% CI: 1.21-7, respectively). High resistance index (> or =0.24), measured by ECDUS, is also an independent risk factor for worsening of EV after B-RTO (HR 4.06, 95% CI: 1.14-14.38) and increase in resistance index is associated with worsening of EV (P for trend=0.028). CONCLUSIONS: The presence of EV, higher Child-Pugh class, and higher resistance index assessed by ECDUS before B-RTO were significant risk factors for worsening of EV after B-RTO.

Prevalence of mid-gastrointestinal bleeding in patients with acute overt gastrointestinal bleeding: multi-center experience with 1,044 consecutive patients.

BACKGROUND: Video capsule endoscopy (VCE) and double-balloon enteroscopy (DBE) enable the detection of small intestinal lesions. AIM: To examine causes of acute overt gastrointestinal (GI) bleeding and the prevalence of mid-GI bleeding, defined as small intestinal bleeding from the ampulla of Vater to the terminal ileum, in a multi-center experience in Japan in the VCE/DBE era. METHODS: Data were collected retrospectively from consecutive patients with acute overt GI bleeding in ten participating hospitals. All patients were examined by esophagogastroduodenoscopy and/or colonoscopy. When the source of bleeding was not identified after these procedures, patients suspected to have mid-GI bleeding were referred to our hospital and VCE/DBE was performed to determine the source of bleeding. RESULTS: Of the 1044 patients with acute overt GI bleeding, 524 (50.2%) patients were diagnosed with upper GI bleeding, 442 (42.3%) with lower GI bleeding, and 13 (1.2%) with mid-GI bleeding. Gastric ulcer was the most common cause of bleeding (20.4%). Among cases of mid-GI bleeding, ulcers were found in 4 (30.8%) patients, erosions in 3 (23.1%), angiodysplasia in 3 (23.1%), submucosal tumor in 2 (15.4%), and hemangioma in one (7.7%). Seven lesions were located in the jejunum, 5 in the ileum, and one in both the jejunum and ileum. Analysis of age-related cause showed that the prevalence of mid-GI bleeding among younger patients under 40 years of age was higher (5%) than in other age groups (1-2%). CONCLUSION: mid-GI bleeding is rare among Japanese patients with acute overt GI bleeding.

Lansoprazole, a Proton Pump Inhibitor, Suppresses Production of Tumor Necrosis Factor-alpha and Interleukin-1beta Induced by Lipopolysaccharide and Helicobacter Pylori Bacterial Components in Human Monocytic Cells via Inhibition of Activation of Nuclear Factor-kappaB and Extracellular Signal-Regulated Kinase.

Pathogenic bacterial components play critical roles in initiation of gastrointestinal inflammation via activation of intracellular signaling pathways which induce proinflammatory cytokines such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta. Lansoprazole (LANSO), a proton pump inhibitor, has been widely used for the treatment of peptic ulcers and reflux esophagitis due to its potent acid-suppressive effect. It has also been reported to have anti-inflammatory effects. In this study we investigated the effects of LANSO on the production of TNF-alpha and IL-1beta induced by lipopolysaccharide (LPS) and Helicobacter pylori water-soluble extract (HpWE) in the human monocytic cell line (THP-1). LANSO (100 microM) significantly reduced mRNA expression and production of TNF-alpha and IL-1beta by THP-1 cells stimulated by LPS and HpWE. LANSO inhibited phosphorylation and degradation of inhibitory factor kappaB-alpha (IkappaB-alpha) and phosphorylation of extracellular signal-regulated kinase (ERK) induced by LPS and HpWE in THP-1 cells. These findings suggest that LANSO exerts anti-inflammatory effects by suppressing induction of TNF-alpha and IL-1beta via inhibition of nuclear factor (NF)-kappaB and ERK activation.

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.

Usefulness of double-balloon endoscopy in the diagnosis of malignant small-bowel tumors.

BACKGROUND & AIMS: Double-balloon endoscopy (DBE) enables endoscopic and histopathologic diagnosis of malignant small-bowel tumors (MSBT). This study examined the clinical features of patients with MSBT and evaluated the usefulness of DBE in the diagnosis of MSBT. METHODS: We retrospectively examined consecutive DBE studies of 358 patients who underwent DBE in our hospital between December 2003 and October 2007 because of suspected or established small-bowel disease. RESULTS: Fourteen patients with MSBT were diagnosed by DBE. The most common type was primary adenocarcinoma (8 patients), followed by metastatic carcinoma (3 patients) and malignant lymphoma (3 patients). Half of these patients presented with obscure gastrointestinal bleeding (OGIB). Histopathologic diagnosis was obtained in 11 of 14 patients. CONCLUSIONS: Of 180 patients with OGIB, MSBT accounted for only 3.9%, however, 50% of patients with MSBT presented with OGIB. OGIB is an important clinical feature of small-bowel malignancy, which can be diagnosed by DBE.