Dabigatran-induced esophagitis: The prevalence and endoscopic characteristics.

BACKGROUND AND AIM: There have been some descriptions of dabigatran-induced esophagitis in the literature. The aim of this study was to examine the prevalence and endoscopic characteristics of the disease. METHODS: We reviewed the endoscopic database and medical records of 91 patients with dabigatran internal use who underwent upper gastrointestinal endoscopy. The frequency of dabigatran-induced esophagitis and its endoscopic findings were retrospectively analyzed. In addition, the clinical characteristics were compared between patients with dabigatran-induced esophagitis and those without the disease. RESULTS: Dabigatran-induced esophagitis was found in 19 of 91 (20.9%) patients. Of the 19 patients with the esophagitis, 18 (94.7%) showed longitudinally sloughing epithelial casts in the mid and/or lower esophagus, which may be characteristic endoscopic findings of this disease. Symptomatic patients were more frequent in patients with dabigatran-induced esophagitis (68.4%) than those without (37.5%, P = 0.02). Other factors including age, gender, coexistence of hiatal hernia, gastroesophageal reflux disease, or concomitant other medications did not differ between the two groups. CONCLUSIONS: Dabigatran causes the esophageal mucosal injury in approximately 20% of patients. Longitudinally sloughing casts in the distal esophagus are characteristic of dabigatran-induced esophagitis.

Serial changes of serum cytokines in Crohn's disease following treatment with adalimumab.

BACKGROUND/AIMS: We examined serum cytokine levels in Crohn's disease (CD) patients before and after Adalimumab (ADA) treatment. METHODOLOGY: A total of 24 patients with CD were enrolled (4 colonic type, 6 ileal type, 14 ileo-colonic type). Patients were divided into two groups according to disease duration. Patients were given ADA (160 mg at week 0 and 80 mg at week 2), followed by maintenance therapy (40 mg every other week). Serum levels of 17 cytokines were simultaneously determined using a Bio-Plex suspension array system before, 4 and 8 weeks after ADA treatment. Serum CRP levels were also measured before, 4 and 8 weeks after treatment. RESULTS: IL-6 and MCP-1 levels were significantly decreased in all CD patients and in the ileo-colonic type 8 weeks after ADA treatment compared to before treatment (P <0.05). MCP-1 levels were significantly decreased 8 weeks after treatment compared to pre-treatment samples if disease onset occurred longer than 8 years. A significant correlation was noted between CRP and IL-6 levels. CONCLUSIONS: The reduction of IL-6 and MCP-1 would be an important role for the improvement of inflammation after ADA treatment in CD which might be associated with disease types and disease duration,

Long-term outcomes of endoscopic submucosal dissection for early gastric cancer: a single-center retrospective study.

BACKGROUND: The aim of the present study was to examine the safety and efficacy of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) based on the long-term outcomes. PATIENTS AND METHODS: From June 2002 to March 2007, ESD was carried out in 472 cases and 570 lesions of EGC. Post-surgical cases and status-unknown cases were excluded. The following long-term outcomes were examined in 438 patients who were reliably followed up for at least 5 years after treatment (range: 5 years [60 months] to 9 years, 9 months [117 months]): local recurrence, metachronous recurrences, and the survival rate. RESULTS: The overall en bloc resection rate was 97.7% for all lesions treated by ESD. The median procedure time was 47.0 min (range 8-345 min). The incidence of positive horizontal andvertical margins was 3.7% and 3.4%, respectively. The incidence of perforation and postoperative bleeding was 5.3% and 4.3%, respectively. There were no deaths related to ESD. Local recurrence was observed in five patients (1.1%), and metachronous recurrences in 7.8% of the patients. The post-treatment 5-year survival was 83.1%. There were no deaths as a result of gastric cancer associated with sites treated by ESD. CONCLUSION: ESD can be considered a standard treatment for EGC based on its expanded indications and low incidences of local recurrence and lymph node metastasis.

The effect of granulocyte and monocyte adsorptive apheresis on serum cytokine levels in patients with ulcerative colitis.

BACKGROUND: Granulocyte and monocyte adsorptive apheresis (GMA) with an Adacolumn has been reported to be effective as induction therapy in ulcerative colitis (UC). However, the effects of GMA on serial changes in cytokine levels have not been well characterized. We therefore, investigated cytokine levels in UC patients before and after treatment with GMA. A total of 16 patients with active UC, 10 men, and six women, mean age, 42.6 years were included. Fourteen patients had total colitis and two patients had left-sided colitis. The study included nine patients with a chronic intermittent course, six with a chronic continuous course and one with a single episode. The duration of each GMA session was 60 min at a flow rate of 30 mL/min as per study protocol. Serum levels of 17 cytokines were determined simultaneously using a Bio-Plex suspension array system before and after treatment with GMA. Serum interleukin (IL)-10 and macrophage inflammatory protein-1ß levels were increased significantly in UC patients after GMA treatment compared to pre-treatment levels (P < 0.05). In particular, GMA treatment caused a significant increase in serum IL-10 levels compared to pre-treatment in patients with total colitis or with a chronic intermittent UC course. In conclusion, this investigation showed that GMA was associated with a marked increase in serum level of the anti-inflammatory cytokine, IL-10. The rise in circulating IL-10 is interesting, and potentially a significant factor in the efficacy of GMA in patients with inflammatory bowel diseases.

Serial changes in cytokine expression in irritable bowel syndrome patients following treatment with calcium polycarbophil.

BACKGROUND/AIMS: Calcium polycarbophil improves abdominal symptoms in patients with irritable bowel syndrome (IBS). We examined cytokine expression in IBS patients before and after administration of calcium polycarbophil. METHODOLOGY: A total of 24 IBS patients (13 diarrhea type, 11 constipation type; median age, 55 years) were enrolled. Serum levels of high sensitive C-reactive protein (CRP) and 17 cytokines (interleukin [IL]-1ß, -2, -4, 5, -6, -7, -8, -10, -12, -13 and -17; tumor necrosis factor-a [TNF-a]; interferon [IFN]-?; granulocyte colony-stimulating factor [G-CSF]; granulocyte macrophage colony-stimulating factor [GM-CSF]; macrophage inflammatory protein [MIP]-1ß; and macrophage chemo-attractant protein [MCP-1]) were simultaneously determined using a Bio-Plex suspension array system before and 12 weeks after administration of calcium polycarbophil 1,500-3,000mg/day. RESULTS: Serum MCP-1 levels in diarrhea type IBS patients were significantly higher than those in constipation type patients (p<0.05). In IBS patients, no significant changes in serum cytokine levels were observed following calcium polycarbophil administration. In constipation type patients, serum high sensitive CRP levels were significantly lower after treatment than before treatment. CONCLUSIONS: Decreases in serum high sensitive CRP levels following calcium polycarbophil treatment may be involved in the relief of abdominal symptoms in IBS patients; diarrhea type IBS is characterized by increased MCP-1 expression.

Effects of proton pump inhibitors in patients with laryngopharyngeal reflux disease.

BACKGROUND/AIMS: The effect of proton pump inhibitors (PPIs) on the health-related quality of life (HRQoL) of patients with laryngopharyngeal reflux disease (LPRD) is not well known. Our aim was to assess the HRQoL before and after administration of a PPI in patients with LPRD. METHODOLOGY: A total of 27 LPRD patients (14 women, 13 men; mean age 54 years) were enrolled. We determined the HRQoL using three different inquiry systems: 1) Frequency Scale for the Symptoms of GERD (FSSG); 2) the 36 item short form of the Medical Outcome Study Questionnaire (SF-36); and 3) the Gastrointestinal Symptom Rating Scale (GSRS). The HRQoL was determined at baseline and after eight weeks of treatment with lansoprazole at a dose of 30mg once daily or rabeprazole at a dose of 10mg once daily. RESULTS: After administration of the PPI, the FSSG, the SF-36 general health scale and mental health scale, GSRS reflux syndrome score, abdominal pain syndrome score and the indigestion syndrome score were significantly improved compared to baseline pretreatment scores (p<0.05). CONCLUSIONS: PPI therapy would be useful for the treatment of LPRD.

Usefulness of endoscopic treatment for duodenal adenoma.

In recent years, due to the increasing prevalence of upper gastrointestinal endoscopy, there have been an increasing number of reports on duodenal adenoma and early stage cancer. However, endoscopic techniques for the resection of duodenal adenomas are difficult, due to the anatomical features of the duodenum, and the long distance to the lesion. There have only been a few reports on the use of endoscopic techniques for duodenal adenomas compared to those focused on the stomach and large intestine. For duodenal adenomas, we used a conventional endoscope for lesions proximal to the major duodenal papilla, and a short-type double balloon endoscope for lesions distal to the papilla. The en-bloc resection rate was 93.8%. There was only one case of microperforation. Endoscopic manipulation is considered difficult in the deep areas of the duodenum, but double balloon endoscopy enabled stable manipulation and successful resection of the tumor in the majority of cases.

Individualized Mutation Detection in Circulating Tumor DNA for Monitoring Colorectal Tumor Burden Using a Cancer-Associated Gene Sequencing Panel.

BACKGROUND: Circulating tumor DNA (ctDNA) carries information on tumor burden. However, the mutation spectrum is different among tumors. This study was designed to examine the utility of ctDNA for monitoring tumor burden based on an individual mutation profile. METHODOLOGY: DNA was extracted from a total of 176 samples, including pre- and post-operational plasma, primary tumors, and peripheral blood mononuclear cells (PBMC), from 44 individuals with colorectal tumor who underwent curative resection of colorectal tumors, as well as nine healthy individuals. Using a panel of 50 cancer-associated genes, tumor-unique mutations were identified by comparing the single nucleotide variants (SNVs) from tumors and PBMCs with an Ion PGM sequencer. A group of the tumor-unique mutations from individual tumors were designated as individual marker mutations (MMs) to trace tumor burden by ctDNA using droplet digital PCR (ddPCR). From these experiments, three major objectives were assessed: (a) Tumor-unique mutations; (b) mutation spectrum of a tumor; and (c) changes in allele frequency of the MMs in ctDNA after curative resection of the tumor. RESULTS: A total of 128 gene point mutations were identified in 27 colorectal tumors. Twenty-six genes were mutated in at least 1 sample, while 14 genes were found to be mutated in only 1 sample, respectively. An average of 2.7 genes were mutated per tumor. Subsequently, 24 MMs were selected from SNVs for tumor burden monitoring. Among the MMs found by ddPCR with > 0.1% variant allele frequency in plasma DNA, 100% (8 out of 8) exhibited a decrease in post-operation ctDNA, whereas none of the 16 MMs found by ddPCR with < 0.1% variant allele frequency in plasma DNA showed a decrease. CONCLUSIONS: This panel of 50 cancer-associated genes appeared to be sufficient to identify individual, tumor-unique, mutated ctDNA markers in cancer patients. The MMs showed the clinical utility in monitoring curatively-treated colorectal tumor burden if the allele frequency of MMs in plasma DNA is above 0.1%.

Colonic transit, bowel movements, stool form, and abdominal pain in irritable bowel syndrome by treatments with calcium polycarbophil.

BACKGROUND/AIMS: Calcium polycarbophil improves abdominal symptoms in patients with irritable bowel syndrome (IBS). We examined colonic transit times in IBS patients both before and after administration of calcium polycarbophil, and clarified the correlations among colonic transit, bowel movements, stool form and abdominal pain. METHODOLOGY: A total of 26 IBS patients (14 diarrhea-predominant type, 12 constipation-predominant type) with a median age of 51 yr were enrolled. Before administration of calcium polycarbophil, mean colonic transit times were calculated from the number of radiopaque markers in the colon. Bowel movements, the stool form scale score and abdominal pain were also measured. After oral administration of calcium polycarbophil for 8 weeks, the transit times were again measured. RESULTS: In diarrhea type, the mean colonic transit time increased, bowel movements decreased in frequency, the stool form scale score decreased, and the abdominal pain appeared to be diminished after treatment (p<0.05). In constipation type, mean colonic transit time decreased, bowel movements increased in frequency, the stool form scale score increased, the abdominal pain appeared to be diminished after treatment (p<0.05). Colonic transit times were highly correlated with stool form or bowel movements. Stool form was also highly correlated with bowel movements before and after treatment. Abdominal pain was significantly correlated with colonic transit before treatment. CONCLUSIONS: Calcium polycarbophil is useful in improving colonic transit, bowel movements, stool form and abdominal pain in both types of IBS. Improvement in colonic transit might relieve abdominal pain in IBS patients.

Unusual Manifestation of Gastric Helicobacter pylori Infection.

Infection with Helicobacter pylori (HP) is common in many parts of the world. While most patients are asymptomatic, it causes peptic ulcer disease and malignancy in some of them. Other rare conditions have occasionally been reported in association with this infection. We report a case of hypertrophic gastropathy caused by HP in a 52-year-old asymptomatic patient. He was found to have marked enlargement of the gastric mucosal folds on radiological imaging and endoscopy. A gastric mucosal biopsy showed HP colonization associated with neutrophilic inflammation. After exclusion of neoplasia, other infections and infiltrative disorders, HP was thought to be the cause of the gastric fold hypertrophy. The patient responded well to HP eradication therapy, with normalization of the gastric mucosal folds. HP infection should be considered in the differential diagnosis of hypertrophic gastropathy and treated accordingly.

Colonic mucosa-associated lymphoid tissue lymphoma.

Colonic mucosa-associated lymphoid tissue (MALT) lymphomas are rare and a definitive treatment has not been established. Solitary or multiple, elevated or polypoid lesions are the usual appearances of MALT lymphoma in the colon and sometimes the surface may reveal abnormal vascularity. In this paper we report our experience with four cases of colonic MALT lymphoma and review the relevant literature. The first patient had a smooth elevated lesion in the rectum and histopathologic examination of the biopsy from the lesion showed centrocyte-like cells infiltrating the lamina propria. Endoscopic ultrasonography (EUS) revealed thickening of the submucosa and muscularis propria. The patient underwent radiation therapy, and 9 months later a repeat colonoscopy showed complete resolution of the lesion. In case 2, colonoscopy showed a polyp in the cecum; the biopsy was diagnostic of MALT lymphoma. EUS detected a hypoechoic lesion confined to the mucosal layer of the colonic wall. The patient underwent endoscopic mucosal resection of the lesion and after 6 years of follow-up there was no evidence of recurrence. The third patient had a sessile elevated lesion in the sigmoid colon for which she underwent sigmoidectomy. Pathological examination of the surgical specimen was suggestive of MALT lymphoma. The last patient had a smooth elevated lesion in the rectum and magnification endoscopy showed irregular vascular pattern. The patient underwent endoscopic submucosal dissection, and biopsy examination showed the tumor to be MALT lymphoma. Although rare, awareness of MALT lymphoma of the colon is important to evaluate the patient appropriately and to plan further management.

Usefulness of double-balloon endoscopy in the postoperative gastrointestinal tract.

Background. The small intestine has been considered to be a highly difficult organ to visualize in imaging examinations due to its anatomical location compared with the stomach and the colon. In recent years, many imaging modalities have become available, such as CT enterography, MR enterography, capsule endoscopy (CE), and double-balloon endoscopy (DBE). Patients and Methods. DBE was performed in the postoperative intestines of 91 patients (128 DBE examinations) at Iwate Medical University between 2004 and 2010. There were 61 male and 30 female patients, and their mean age was 69.7 years (range: 30-80 years). Results. A total of 124 DBE examinations were performed with endoscope insertion into the reconstructed intestines. The endoscope reached the blind end in 115 of 124 examinations, (92.7%). There were 17 patients with obscure gastrointestinal bleeding in whom 30 DBE examinations were performed. The bleeding site was identified in 12 patients (70.6%). Nine patients underwent endoscopic treatment. Hemostasis was achieved in all patients. Conclusion. DBE is very useful modality for the assessment and application of endotherapy to areas of the small bowel which have been altered by surgery.

Peripheral Blood CD64 Levels Decrease in Crohn's Disease following Granulocyte and Monocyte Adsorptive Apheresis.

Granulocyte and monocyte adsorptive apheresis (GMA) is reportedly useful as induction therapy for Crohn's disease (CD). However, the effects of GMA on CD64 have not been well characterized. We report here our assessment of CD64 expression on neutrophils before and after treatment with GMA in two patients with CD. The severity of CD was assessed with the CD activity index (CDAI). The duration of each GMA session was 60 min at a flow rate of 30 ml/min as per protocol. CD64 expression on neutrophils was measured by analyzing whole blood with a FACScan flow cytometer. In case 1, CD64 levels after each session of GMA tended to decrease compared to pretreatment levels, whereas in case 2, CD64 levels dropped significantly after treatment. The CDAI decreased after GMA in both cases 1 and 2. A significant correlation was noted between CDAI scores and CD64 levels in both cases. In conclusion, GMA reduced blood CD64 levels, which would be an important factor for the decrease of CDAI scores.

Appropriate cut-off value of 13C-urea breath test after eradication of Helicobacter pylori infection in Japan.

BACKGROUND AND AIM: A cut-off value of 2.5 per thousand for the 13C-urea breath test (UBT) is recommended in Japanese persons, based on the result of a multicenter trial in patients prior to treatment for eradication of Helicobacter pylori. The cut-off value of 2.5 per thousand has also been used in the assessment of eradication after treatment. The 6-8-week evaluation after treatment is recommended in the guidelines of the Japanese Society of Gastroenterology. The present study aimed to prospectively re-assess the cut-off value of the 13C-UBT at 6 weeks after treatment by using the results obtained at 6 months as an indication of true positive or true negative H. pylori infection status. METHODS: One hundred and ninety patients who were positive for H. pylori underwent eradication treatment, and 177 patients of these patients who were assessed as having true positive or true negative H. pylori status at 6 months after treatment were evaluated in this study. Eradication was assessed by 13C-UBT, culture, and histology at 6 weeks and at 6 months after treatment, and the cut-off value of 13C-UBT at 6 weeks was re-assessed. RESULTS: A cut-off value of 3.5 per thousand. at 6 weeks after treatment showed 97.2% diagnostic accuracy, while a cut-off value of 2.5 per thousand at 6 weeks showed 96.0% diagnostic accuracy. For a 3.5 per thousand cut-off value, only five patients were positive by 13C-UBT and were negative by culture and histology at 6 weeks, and three patients were true positive and two were false positive by the 13C-UBT at 6 months. CONCLUSION: A cut-off value of 3.5 per thousand for the 13C-UBT is recommended at 6 weeks after eradication treatment in Japanese persons.