Multicenter feasibility study of bowel preparation with castor oil for colon capsule endoscopy.

BACKGROUND AND AIM: Extensive use of laxatives and incomplete excretion rates are problematic for colon capsule endoscopy (CCE). The aim of the present study was to determine the effectiveness of castor oil as a booster. METHODS: At four Japanese hospitals, 319 examinees undergoing CCE were enrolled retrospectively. Before and after the introduction of castor oil, other preparation reagents were unchanged. RESULTS: Of 319 examinees who underwent CCE, 152 and 167 examinees took regimens with castor oil (between November 2013 and June 2016) and without castor oil (between October 2015 and September 2017), respectively. Capsule excretion rates within its battery life in the groups with and without castor oil were 97% and 81%, respectively (P < 0.0001). Multivariate analysis showed that ages younger than 65 years (adjusted odds ratio [OR], 3.00; P = 0.0048), male gender (adjusted OR, 3.20; P = 0.0051), and use of castor oil (adjusted OR, 6.29; P = 0.0003) were predictors of capsule excretion within its battery life. Small bowel transit time was shorter and total volume of lavage and fluid intake was lower with castor oil than without (P = 0.0154 and 0.0013, respectively). Overall adequate cleansing level ratios with and without castor oil were 74% and 83%, respectively (P = 0.0713). Per-examinee sensitivity for polyps ≥6 mm with and without castor oil was 83% and 85%, respectively, with specificities of 80% and 78%, respectively. CONCLUSION: Bowel preparation with castor oil was effective for improving capsule excretion rate and reducing liquid loading.

Novel findings of capsule endoscopy and double-balloon enteroscopy in a case of eosinophilic gastroenteritis.

Eosinophilic gastroenteritis is a rare disease with unknown cause. It is characterized by marked eosinophilic infiltration in the gastrointestinal tract. There are few reports that include detailed endoscopic findings of eosinophilic gastroenteritis in the small intestine. A 48-year-old man complaining of abdominal pain was admitted to our hospital. A complete blood count showed eosinophilia, and ascites showed eosinophilia. Abdominal computed tomography indicated dilation, wall thickening of the small intestine, and ascites. Capsule endoscopy revealed stenosis, dilation, edematous mucosa, and aperistalsis in the upper jejunum, together with circumferential ulcerated lesions and ulcer scars in the ileum. Double-balloon enteroscopy revealed a 10-cm segmental mucosal edema and stenosis in the ileum. In one segment, there were several circumferential ulcerated lesions. These lesions included both small round ulcers and large ulcers with redness and mucosal edema. Histological examination revealed infiltration of eosinophils into biopsy specimens of the ileum. The patient was diagnosed with eosinophilic gastroenteritis. The patient recovered after rehydration therapy. After 9 months, capsule endoscopy revealed no ulcers or edema. In this report, we describe the findings of capsule endoscopy and double-balloon enteroscopy in a case of eosinophilic gastroenteritis.

Successful endoscopic injection sclerotherapy of high-risk gastroesophageal varices in a cirrhotic patient with hemophilia A.

A 68-year-old man with hemophilia A and liver cirrhosis caused by hepatitis C virus was referred to our hospital to receive prophylactic endoscopic treatment for gastroesophageal varices (GOV). He had large, tense, and winding esophageal varices (EV) with cherry red spots extending down to lesser curve, predicting the likelihood of bleeding. Esophageal endoscopic injection sclerotherapy (EIS) was performed with a total 15 mL of 5% ethanolamine oleate with iopamidol (EOI). Radiographic imaging during EIS demonstrated that 5% EOI reached the afferent vein of the varices. He was administered sufficient factor VIII concentrate before and after EIS to prevent massive bleeding from the varices. Seven days after EIS, upper gastrointestinal endoscopy (UGIE) showed that the varices were eradicated almost completely. Eighteen months after EIS, the varices continued to diminish. We report a successful case of safe and effective EIS for GOV in a high-risk cirrhotic patient with hemophilia A.

Tissue factor pathway inhibitor 2 (TFPI2) is frequently silenced by aberrant promoter hypermethylation in gastric cancer.

Aberrant methylation of promoter CpG islands is associated with transcriptional inactivation of tumor-suppressor genes in cancer. TFPI2, a Kunitz-type serine proteinase inhibitor, has been identified as a putative tumor-suppressor gene from genome-wide screening for aberrant methylation, using a microarray combined with the methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-aza-dCyd) in various types of tumors. We assessed the methylation status of TFPI2 and investigated its expression pattern in human primary gastric cancer (GC) tissues and in GC cell lines. Hypermethylation of the promoter CpG island, which was observed in more or less all of GC cell lines, was prevalent in a high proportion of primary GC tissues (15/18, or 83%), compared with noncancerous (4/18, or 22%) or normal (0/3, or 0%) stomach tissues, and expression of TFPI2 mRNA was reduced in 7 of the 17 primary GC tissues (41%). Moreover, immunohistochemical analyses showed decreased levels of TFPI-2 protein, compared with adjacent noncancerous tissues in 8 of the 20 primary GC tissues examined (40%). TFPI2 mRNA expression was restored in gene-silenced GC cells after treatment with 5-aza-dCyd. Aberrant methylation of TFPI2 promoter CpG island occurred not only in GC cells but also in primary GC tissues at a high frequency, suggesting that epigenetic silencing of TFPI2 may contribute to gastric carcinogenesis.

Epigenetic silencing of RELN in gastric cancer.

RELN (Reelin) is an extracellular glycoprotein that plays a critical role in neuronal migration. Here we show that the RELN gene is frequently silenced in gastric cancers (GCs) by aberrant promoter hypermethylation. Although RELN was strongly expressed in non-tumor gastric epithelia, its expression was weak, or absent, in GC cell lines and primary GC tumors. Absence of RELN expression significantly correlated with a more advanced stage of GC. Methylation of the RELN promoter was frequently found in GC cell lines and in primary GC tumors. These findings suggest that disruption of the RELN pathway may be involved in gastric carcinogenesis.

MELD score, child-pugh score, and decreased albumin as risk factors for gastric variceal bleeding.

BACKGROUND/AIMS: Ruptured esophagogastric varices are commonly associated with bleeding in patients with portal hypertension. However, the prediction of esophageal variceal bleeding is not matched by means of predicting gastric variceal bleeding. The present study aim is to elucidate risk factors for gastric variceal bleeding. METHODOLOGY: Twelve patients with gastric variceal bleeding and 18 patients receiving preventive treatment for gastric varices were included in the study. RESULTS: The Child-Pugh (8.0 +/- 0.9 vs. 5.5 +/- 0.3; p = 0.0025) and Model for end-stage liver disease (MELD) (10.6 +/- 2.7 vs. 4.0 +/- 0.9; p = 0.0095) scores were significantly higher for patients with bleeding than for those receiving preventive treatment. Serum albumin concentration was significantly lower in bleeding than in preventive treatment cases, as determined by univariate (2.9 +/- 0.2 vs. 3.7 +/- 0.1 mg/dL; p < 0.0001) and multivariate analyses of serological data (odds ratio, 0.02, 95% confidence interval, 0.001-0.479; p = 0.0144). CONCLUSIONS: The Child-Pugh and MELD scores were significantly higher for patients with gastric variceal bleeding than for those receiving preventive treatment, and multivariate analysis revealed that serum albumin was significantly lower in patients with gastric variceal bleeding. Control of serum albumin is important in preventing gastric variceal bleeding.

Comparison of endoscopic findings with symptom assessment systems (FSSG and QUEST) for gastroesophageal reflux disease in Japanese centres.

BACKGROUND AND AIM: We compared endoscopic findings of the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG), a written questionnaire developed in Japan, to that for the questionnaire for the diagnosis of reflux esophagitis (QUEST) for the diagnosis of reflux esophagitis. METHODS: We registered 475 patients with untreated symptoms of upper abdominal pain (male/female: 252/223, average age 52.4 +/- 17.8 years). Subjects were assessed first with the FSSG and QUEST questionnaires, then by endoscopy, before allocation to a gastric ulcer (GU), duodenal ulcer (DU), gastroesophageal reflux disease (GERD) or functional dyspepsia (FD) group. RESULTS: On the basis of the endoscopic findings the diagnoses for the 475 subjects were as follows: FD 52.2%, DU 7.6%, GU 7.8%, and GERD 32.4% (Grade M 10.1%, Grade A + B 20.2%, Grade C + D 2.3%). There was no difference between the FSSG and QUEST in sensitivity, specificity or accuracy for any condition. The FSSG score rose with increasing endoscopic severity of GERD, but there was no correlation between the QUEST score and endoscopic severity. The FSSG total score was inferior to QUEST in terms of distinguishing GERD from other conditions, but when only the questions relating to reflux symptoms were used, the FSSG was able to distinguish GERD from other conditions as well as QUEST. CONCLUSIONS: The FSSG score reflects the severity of the endoscopic findings of GERD.

ERK5 is a target for gene amplification at 17p11 and promotes cell growth in hepatocellular carcinoma by regulating mitotic entry.

Using high-density oligonucleotide microarrays, we investigated DNA copy-number aberrations in cell lines derived from hepatocellular carcinomas (HCCs) and detected a novel amplification at 17p11. To identify the target of amplification at 17p11, we defined the extent of the amplicon and examined HCC cell lines for expression of all seven genes in the 750-kb commonly amplified region. Mitogen-activated protein kinase (MAPK) 7, which encodes extracellular-regulated protein kinase (ERK) 5, was overexpressed in cell lines in which the gene was amplified. An increase in MAPK7 copy number was detected in 35 of 66 primary HCC tumors. Downregulation of MAPK7 by small interfering RNA suppressed the growth of SNU449 cells, the HCC cell line with the greatest amplification and overexpression of MAPK7. ERK5, phosphorylated during the G2/M phases of the cell cycle, regulated entry into mitosis in SNU449 cells. In conclusion, our results suggest that MAPK7 is likely the target of 17p11 amplification and that the ERK5 protein product of MAPK7 promotes the growth of HCC cells by regulating mitotic entry.

Sildenafil, an inhibitor of phosphodiesterase subtype 5, prevents indomethacin-induced small-intestinal ulceration in rats via a NO/cGMP-dependent mechanism.

We examined the effect of sildenafil, an inhibitor of phosphodiesterase subtype 5, that catalyzes hydrolysis of 3',5'-cyclic guanosine monophosphate (cGMP), on indomethacin-induced small-intestinal ulceration in rats and investigated the mechanism of this action, especially in relation to endogenous nitric oxide (NO). Animals without fasting were given indomethacin (10 mg/kg) s.c. and then killed 24 h later. Indomethacin produced hemorrhagic lesions in the small intestine, accompanied by a promotion of enterobacterial invasion and the expression of inducible NO synthase (iNOS) as well as myeloperoxidase (MPO) activity in the mucosa. Sildenafil (3-20 mg/kg), given p.o. 30 min before indomethacin, dose-dependently reduced the severity of these lesions, with concomitant suppression of the increase in MPO activity, iNOS expression and bacterial invasion. These effects were attenuated by the prior administration of the nonselective NOS inhibitor, N (G)-nitro-L-arginine methyl ester, in an L-arginine-reversible manner. Indomethacin also decreased the secretion of mucus and fluid (enteropooling) and enhanced intestinal motility, but these responses were all prevented by the prior administration of sildenafil. Likewise, pretreatment of the animals with NOR-3, a NO donor, also reversed the functional changes caused by indomethacin, followed by suppression of bacterial invasion and iNOS expression, and prevented the development of intestinal lesions. These results suggest that sildenafil prevents indomethacin-induced small-intestinal ulceration in rats, via a NO/cGMP-dependent mechanism, and this effect is functionally associated with an increase in the secretion of mucus/fluid and a decrease of hypermotility, resulting in the suppression of bacterial invasion and iNOS expression following indomethacin treatment.

Clostridium difficile-associated diarrhea with hematochezia is associated with ulcer formation.

OBJECTIVE: Clostridium difficile-associated diarrhea (CDAD) is a well-known iatrogenic infection with typical endoscopic features including pseudomembranes and intervening normal mucosa. Clinically, diarrhea frequently occurs, but occurrence of hematochezia is rare. The objective of this study was to investigate the background and endoscopic features of CDAD patients with hematochezia. MATERIAL AND METHODS: The endoscopic and clinical findings in 12 patients who showed evidence of C. difficile toxin A and who underwent colonoscopy between April 2002 and July 2007 were investigated retrospectively. RESULTS: Eight patients were diagnosed as having CDAD and 4 patients had a diagnosis of ulcerative colitis. Six of the patients with CDAD presented with hematochezia, and 4 of them were diagnosed with hematological malignancies and received anticancer chemotherapy. Colonic ulcer was demonstrated in all CDAD patients with hematochezia, and bleeding from the ulcer was endoscopically confirmed in all of them. CONCLUSIONS: CDAD accompanied by hematochezia is closely associated with ulcer formation. Ulcers are thought to occur during recovery from nadir after anticancer treatment, and white blood cells appear to be essential for their formation. Physicians should therefore pay close attention to the occurrence of colonic ulcer, especially in patients with CDAD during recovery from nadir.

Dual role of nitric oxide in gastric hypersecretion in the distended stomach: inhibition of acid secretion and stimulation of pepsinongen secretion.

AIMS: We investigate the role of nitric oxide (NO) in the hypersecretion of acid and pepsinogen induced by stomach distension. MAIN METHOD: The rat stomach was distended by instillation of saline through an acute fistula under urethane anesthesia. KEY FINDINGS: Both secretions of acid and pepsinogen were increased by the distension depending on the volume of saline introduced, and responses were attenuated by bilateral cervical vagotomy or prior administration of atropine. N(G)-nitro-l-arginine methyl ester (L-NAME) had a dual effect on these responses, causing an increase in the acid response and a decrease in the pepsin response, both in an l-arginine-sensitive manner. Distension of the stomach increased the luminal NO release; this response was suppressed by vagotomy and L-NAME. Intragastric application of FK409, a NO donor, dose-dependently increased pepsinogen secretion while decreasing acid secretion in the stomach without distension. However, serosal application of both FK409 and 8-bromo-guanosine cyclic 3', 5'-monophosphate (8-Br-cGMP) stimulated the secretion of pepsinogen in isolated mouse stomachs in vitro. The stimulatory effect of FK409 on pepsinogen secretion was totally abolished by LY83583, a guanylate cyclase inhibitor. SIGNIFICANCE: Distension of the stomach increases both acid and pepsinogen secretion through a vagal-cholinergic pathway in addition to the luminal release of NO, and NO affects these responses in opposite ways, suppressing the acid response while enhancing the pepsin response, both mediated by a guanylate cyclase/cGMP pathway.

Alteration of the expression profiles of acidic mucin, sialytransferase, and sulfotransferases in the intestinal epithelium of rats infected with the nematode Nippostrongylus brasiliensis.

Acidic mucins such as sialomucin and sulfomucin produced by intestinal epithelial cells have been implicated in the protection of the mucosa from pathogens. In the present study, we analyzed the alteration of acidic mucins in the jejunum of euthymic and athymic rats infected with the nematode Nippostrongylus brasiliensis using alcian blue staining and a high iron-diamine method. The numbers of sialomucin+ goblet cells increased markedly 7 and 10 days post-infection and decreased gradually thereafter in euthymic rats, while athymic rats did not show sialomucin+ goblet cell hyperplasia at least until 28 days post-infection, suggesting that sialomucin production might be regulated by thymus-derived T cells. On the other hand, the numbers of sulfomucin+ goblet cells increased markedly 28 days post-infection in both euthymic and athymic rats despite the fact that sulfomucin+ goblet cell numbers in uninfected athymic rats were significantly smaller than in euthymic rats. Real-time polymerase chain reaction studies on the gene transcription levels of O-glycan sulfotransferases Gal3ST1, Gal3ST2, Gal3ST3, and Gal3ST4 in the jejunal epithelium increased gradually toward day 28 post-infection in euthymic and athymic rats. These results suggest that the production of sulfomucin and expression of Gal3STs are inducible by nematode infection without the activation of thymus-derived T cells.

Acute pancreatitis from mumps re-infection in adulthood. A case report.

CONTEXT: Acute pancreatitis is a complication of mumps which mainly affects children who then usually acquire permanent immunity. We present the case of a woman with acute pancreatitis caused by mumps re-infection in adulthood. CASE REPORT: A 34-year-old woman developed mild acute pancreatitis caused by re-infection with mumps, as confirmed serologically by enzyme-linked immunosorbent assays mumps-specific IgM and IgG. Acute pancreatitis was indicated by the elevation of amylase and other pancreatic enzymes such as lipase and elastase-1 as well as by swelling of the pancreatic head visualized by abdominal computed tomography. The abdominal symptoms were resolved soon after the administration of a pancreatic enzyme inhibitor. As the swelling of the right and left parotids decreased, serum amylase levels also gradually normalized. CONCLUSION: We believe that this is the first reported case of acute pancreatitis caused by mumps re-infection in an adult. Such re-infection should be considered a possible though rare cause of acute pancreatitis in adulthood.

Levels of interleukin-18 are markedly increased in Helicobacter pylori-infected gastric mucosa among patients with specific IL18 genotypes.

BACKGROUND: The cellular immune response in gastric mucosa infected with Helicobacter pylori is proposed to be predominantly of the T helper cell type 1 type. METHODS: Interleukin (IL)-18, IL-12, and interferon (IFN)-gamma levels were measured in gastric mucosal biopsy specimens by reverse-transcription polymerase chain reaction (PCR) and by enzyme-linked immunosorbent assay; IL18 polymorphisms were determined by PCR. RESULTS: Biopsy specimens from 128 patients (56 with nonulcer dyspepsia, 28 with gastric ulcers, 28 with duodenal ulcers, and 16 with gastric cancer) were examined; 96 patients had H. pylori infection. IL-18 levels were markedly up-regulated in mucosa infected with H. pylori (P < .001), whereas IL-12 and IFN-gamma levels were independent of H. pylori status. IL-18 levels correlated with IFN-gamma levels only in infected patients (R = 0.31 to R = 0.51). IL-18 levels were the determining factor for monocyte infiltration in H. pylori-infected mucosa (P < .001). H. pylori-infected patients displaying IL18 -607C/C and -137G/G had higher IL-18 levels than did those with other genotypes and were more likely to experience treatment failure. CONCLUSION: H. pylori infection induces IL-18 in the gastric mucosa. H. pylori-infected patients with IL18 -607C/C and -137G/G have higher IL-18 levels, which causes severe gastric inflammation. IL18 genotype might be a marker for predicting the effects of eradication therapy.

Clear cell adenocarcinoma of the colon: a case report and review of literature.

A primary clear cell adenocarcinoma of the colon is a rare oncologic entity. We herein report a case of such a tumor of the sigmoid colon in a 71-year-old woman who was successfully treated by an endoscopic polypectomy in our hospital. We also reviewed the published reports regarding cases of primary clear cell tumors in the colon.

[A case of adult-onset type II citrullinemia having a liver histology of nonalcoholic steatohepatitis (NASH)].

A 47-year man was hospitalized to our hospital because of consciousness disturbance. He had been abnormally fond of soy bean products since childhood. His plasma levels of ammonia and citrulline were elevated, and we suspected of adult-onset type II citrullinemia (CTLN2). Gene examination demonstrated abnormality in the SLC25A13 gene, confirming CTLN2. Serum levels of hepatobiliary enzymes were increased and his liver biopsy revealed nonalcoholic steatohepatitis. Although we considered that living donor liver transplantation was suitable for the treatment, unfortunately, there was no appropriate donor candidate in his family. He has received conservative treatments, showing a symptom-free course.

IL-17 is involved in Helicobacter pylori-induced gastric inflammatory responses in a mouse model.

BACKGROUND: Helicobacter pylori (H. pylori) is the major cause of chronic active gastritis and peptic ulcer disease. Recent studies have shown that H. pylori produces various cytokines that are related to neutrophil or mononuclear cell accumulation. Interleukin-17 (IL-17) is the founding member of an emerging family of inflammatory cytokines whose biological activities remain incompletely defined. In this study, the contributions of IL-17 to the induction of gastric inflammation and to the protection from H. pylori infection were investigated using IL-17 gene-knockout (IL-17(-/-)) mice. MATERIALS AND METHODS: IL-17(-/-)and wild-type C57BL/6 mice were challenged with H. pylori CPY2052 (2 x 10(8) CFU/mL) and the histological and microbiological evaluation were carried out at specified times. IL-17 and myeloperoxidase (MPO) protein levels in tissues were assayed in duplicate using ELISA kits. RESULTS: In wild-type mice, IL-17 was undetected at baseline; however, the protein expression of IL-17 was induced after infection with H. pylori. A severe infiltration of neutrophils appeared in the submucosa and the lamina propria in wild-type mice. In contrast, the degree of neutrophil infiltration in IL-17(-/-) mice was significantly lower than that in wild-type mice. Although wild-type mice infected with H. pylori showed drastically higher MPO activity compared with uninfected wild-type mice, any significant increase in the enzyme activity was not revealed in infected IL-17(-/-) mice. The number of H. pylori colonized in the stomach of IL-17(-/-) mice was significantly lower than that of wild-type mice from 1 to 6 months after infection. CONCLUSIONS: These results suggest that IL-17 may play an important role in the inflammatory response to the H. pylori infection and ultimately influence the outcome of the H. pylori-associated disease.