The association among enterobacterial flora, dietary factors, and prognosis in patients with ulcerative colitis.

The role of enterobacterial flora in the onset and progression of inflammatory bowel diseases is a topic of considerable interest. Here, we assessed the association among enterobacterial flora, dietary factors, and ulcerative colitis (UC) progression. Forty-six patients with UC who were diagnosed as being in remission were enrolled. We collected each patient's stool sample one or two days before diagnostic colonoscopy. After colonoscopy, we observed the patients for one year and then retrospectively divided them into two groups: remission (n = 39) and relapse (n = 7) groups, depending on whether the relapse occurred during the follow-up period, and analyzed the relationship among patient characteristics, dietary factors, enterobacterial flora, and UC relapse. Overall, there were no significant differences in bacterial community populations between the remission and relapse groups, except that the order Lactobacillales was detected at a significantly higher rate in the relapse than in the remission group (100% vs 71.4%, p<0.05). Vitamin C intake was significantly higher in the remission than in the relapse group (p<0.05). Although there were no obvious differences in enterobacterial flora between the remission and relapse groups, there was a relationship among enterobacterial flora, diet, and UC progression. Given that the enterobacterial flora was only analyzed at the initiation of the study, we conclude that in future analyses, enterobacterial flora should be sampled at numerous time points to examine its role in UC progression. Further long-term longitudinal studies examining enterobacterial flora, dietary factors, and UC progression are also required.

Convenient Method of Measuring Baseline Impedance for Distinguishing Patients with Functional Heartburn from those with Proton Pump Inhibitor-Resistant Endoscopic Negative Reflux Disease.

BACKGROUND: Combined 24-h intraesophageal pH-multichannel intraluminal impedance (24MII-pH) used for assessing gastroesophageal reflux disease by measuring baseline impedance (BI) requires a 24-h measuring period. In the present study, we developed a quick method of measuring BI and evaluated its usefulness in classifying patients with proton pump inhibitor (PPI)-refractory non-erosive reflux diseases (NERD) as having functional heartburn (FH) or endoscopic-negative reflux disease (ENRD). METHODS: Ninety-one NERD patients without esophageal motility disorder underwent 24MII-pH monitoring while on a PPI. The measurements of the mean nocturnal BI (MNBI) and short MNBI were assessed at 3 times (at about 1: 00, 2: 00, and 3: 00 am) for 10 min and 30 s respectively. The measurement of the simple mean BI (MBI) was performed once 30 s at about 11: 00 am. RESULTS: Ninety-one patients were divided into 2 groups: 59 with ENRD and 32 with FH. The cutoff, specificity, and sensitivity for distinguishing patients with FH were as follows: MNBI, 2,874.1 Ω, 72%, and 72%; short MNBI, 2,857.6 Ω, 74%, and 84%; and simple MBI, 2,874.1 Ω, 86%, and 78% respectively. CONCLUSION: Measuring the simple MBI is a quick method and is useful for distinguishing patients with FH from those in a cohort with PPI-refractory NERD.

Characteristics and Predictive Factor of Helicobacter pylori-Associated Functional Dyspepsia in Japanese Patients.

BACKGROUND/AIM: Helicobacter pylori (HP) eradication therapy was first recommended as pharmacotherapy for functional dyspepsia (FD). However, the mechanism and effect of eradication on FD symptom improvement have not been fully investigated. This study aimed to investigate the pathology of patients with HP-associated FD, and predictive factors for HP-associated FD. METHODS: Ninety-seven patients with chronic gastritis caused by HP infection were divided into the group with FD symptoms and the group -without FD symptoms. Patient backgrounds, QOL, gastric mucosal atrophy severity, and serum pepsinogen (PG) value were compared between the 2 groups. Twelve months after eradication, those factors were evaluated between HP-associated FD and HP-non-associated FD, and predictive factors of HP-associated FD were analyzed. RESULTS: The FD-positive group existed in 45 (46.3%) out of 97 patients. Twelve months after eradication, there were 34 patients (75.6%) in the HP-associated FD. The mean PG I value in the HP-associated FD was significantly lower than that in the HP-non-associated FD, while the PG II values in the HP-associated FD tended to be lower than those in the HP-non-associated FD. QOL in the HP-associated FD significantly improved after HP eradication. On multivariate logistic regression analysis, it was found that PG II value was a significant predictive factor for FD symptom improvement in the HP-associated FD. CONCLUSION: HP eradication is an effective initial therapy for FD. PG II value is considered a predictive factor for FD symptom improvement through HP eradication.

Impact of Comorbid Irritable Bowel Syndrome on Treatment Outcome in Non-Erosive Reflux Disease on Long-Term Proton Pump Inhibitor in Japan.

BACKGROUND/AIMS: Irritable bowel syndrome (IBS) frequently coexists with non-erosive reflux disease (NERD). Efficacy of long-term proton pump inhibitor (PPI) treatment on NERD with or without IBS is controversial. The impact of comorbid IBS in NERD on quality of life (QOL) remains uncertain. We verified the hypothesis that NERD patients with IBS symptoms demonstrated poor responses to long-term PPI treatments, deteriorated QOL, and high frequency of psychological deviations in Japan. METHODS: In all, 141 NERD patients who had been taking PPIs for more than 6 months were enrolled and analyzed. Patient profiles were assessed by GerdQ, IBS Severity Index (IBSSI-J)/Gastrointestinal Symptoms Rating Scale (GSRS)/SF-8, and Hospital Anxiety and Depression Scale (HADS). RESULTS: IBS existed in 37 out of 141 NERD patients. Patients with IBS (the positive-IBS group) demonstrated significantly higher frequencies of extant reflux symptoms than those without IBS (64.9 vs. 40.4%). In the positive-IBS group, 40.5% were classified as middle grade by IBSSI-J. The SF-8 and GSRS scores in this group were significantly lower than those without IBS (the negative-IBS group). Prevalence of depression and anxiety by HADS in the positive-IBS group was significantly higher than that in the negative-IBS group. CONCLUSION: These results proved the hypothesis that considering comorbid IBS among NERD patients on long-term PPI seems recommended in Japan.

Urgent colonoscopy is not necessary in case of colonic diverticular bleeding without extravasation on contrast-enhanced computed tomography.

BACKGROUND AND AIMS: Acute lower gastrointestinal bleeding (ALGIB) increase with age and the administration of antiplatelet drugs. Colonic diverticular bleeding (CDB) is the most common cause of ALGIB, and endoscopic hemostasis is an effective treatment for massive CDB. But in patients without extravasation on contrast-enhanced computed tomography (CECT), the efficacy of urgent colonoscopy (UCS) is controversial from the point of the clinical course, including rebleeding rate. We aimed to establish a potential strategy including UCS for CDB patients without extravasation on CECT. PATIENTS AND METHODS: Patients from two centers treated for CDB without extravasation on CECT between July 2014 and July 2019 were retrospectively identified (n = 282). Seventy-four underwent UCS, and 208 received conservative management. We conducted two analyses. The first analysis investigates the risk factors of rebleeding rate within 5 days after administration (very early rebleeding), and no UCS (NUCS) was not the independent factor of the very early rebleeding. The second analysis is whether UCS positively influenced the clinical course after hospitalization. RESULTS: The prevalence of very early rebleeding and early rebleeding (6-30 days from admission), patients requiring blood transfusion within 0-5 days and 6-30 days post-admission, and duration of hospitalization were examined as clinical course factors between UCS and NUCS group. There was no significant difference between the UCS and non-UCS groups in the clinical course factors. UCS for the CDB patients without extravasation was not improved rebleeding rate and clinical course. CONCLUSIONS: UCS is not necessary in case ofCDB patient without extravasation on CECT.

A Vonoprazan, Clarithromycin, and Metronidazole Regimen as Helicobacter pylori Eradication Therapy for Patients with Penicillin Allergy in Light of Clarithromycin Resistance.

Objective Vonoprazan (VPZ), clarithromycin (CAM), metronidazole (MNZ) and VPZ, MNZ, and sitafloxacin (STFX) regimen are all established Helicobacter pylori eradication therapies for patients with penicillin allergy in Japan. However, no study has assessed the efficacy of a VPZ, CAM, and MNZ (VCM) regimen in patients with clarithromycin resistance (CAM-R). We therefore assessed the efficacy of a VCM regimen for treating H. pylori infection in patients with CAM-R and penicillin allergy. Methods Fifty-three patients with penicillin allergy who received H. pylori eradication therapy were retrospectively analyzed. Eight patients received a 7-day proton-pump inhibitor, CAM, and MNZ (PCM) regimen; 35 patients [11 CAM-R, and 10 with clarithromycin sensitivity (CAM-S)] received 7-day VCM regimens; and 10 patients received 7-day VPZ, MNZ, and STFX (VMS) regimens. A 13C-urea breath test was used to determine eradication. The efficacy of eradication was evaluated via both intention-to-treat (ITT) and per-protocol (PP) analyses. Results According to ITT and PP analyses, eradication rates (ERs) with PCM, VCM, and VMS therapies were 50.0% and 50.0%, 94.3% and 100%, and 90% and 90%, respectively. Treatment was successful in all patients with CAM-S. For patients with CAM-R, treatment was successful in 10 patients, and 1 patient discontinued treatment owing to an adverse event. According to ITT and PP analyses, ERs were 90.9% and 100% in CAM-R, and were 100% and 100% in CAM-S, respectively. Conclusion The VCM regimen for H. pylori eradication may be a viable candidate therapy for patients with penicillin allergy, regardless of CAM-R.

Effects of acotiamide on functional dyspepsia patients with heartburn who failed proton pump inhibitor treatment in Japanese patients: A randomized, double-blind, placebo-controlled crossover study.

BACKGROUND: Functional dyspepsia (FD) and non-erosive reflux disease (NERD) are gastrointestinal disorders that often overlap. In this randomized, double-blind, placebo-controlled crossover study, the effects of adding acotiamide to treatment with proton pump inhibitors (PPI) were investigated in FD patients with heartburn who failed PPI treatment, corresponding to PPI-resistant NERD. METHODS: The subjects included 16 FD patients with heartburn who failed PPI treatment, and they were administered acotiamide or a placebo for 28 days. After suspending medication for 28 days, the trial drug and placebo were crossed over and administered for 28 days. Before the study began and after each administration period, high-resolution impedance manometry (HRiM) was performed, and the modified frequency scale for the symptoms of gastroesophageal reflux disease (FSSG) questionnaire was administered. KEY RESULTS: Postprandial fullness in the FD assessment and all modified FSSG items were significantly lower in the acotiamide group than in the placebo group. Esophagogastric junction pressure was significantly higher in the acotiamide group. The distal contractile integral (DCI) pressure and the highest DCI pressure both increased significantly in the acotiamide group. Moreover, in the acotiamide group, the frequency of abnormal primary peristalsis decreased to normal levels; complete bolus transit (CBT), an indicator of esophageal clearance, increased; and CBT time decreased. CONCLUSIONS & INFERENCES: Acotiamide was considered to improve upper gastrointestinal functions not only in the stomach but also in the esophagus. Adding acotiamide to PPI therapy appears to improve upper abdominal symptoms in FD patients with heartburn who failed PPI treatment.

Markedly Effective Steroid Treatment of Three Patients with Allergy-related Jackhammer Esophagus.

We experienced marked efficacy with steroid treatment of three patients with jackhammer esophagus (JHE). An esophageal biopsy revealed eosinophilic esophagitis (EoE) in two patients. One of the patients without EoE had eosinophilia and an increased serum immunoglobulin E level, and endoscopic ultrasonography revealed thickening of the esophageal muscularis propria. Esophageal manometry was used to diagnose all cases of JHE. Treatment consisted of steroid administration, which improved the symptoms and resolved the esophageal muscularis propria thickening in all patients. The esophageal manometry findings also normalized following treatment. Allergic diseases, including EoE, were assumed to have caused JHE.

Gastric schwannoma with high accumulation on fluorodeoxyglucose-positron emission tomography resected by non-exposed endoscopic wall-inversion surgery.

Gastric schwannoma is a relatively rare tumor arising from Auerbach plexus in the muscle layer of the gastric wall, and constitutes 0.1% to 0.2% of all gastric tumors and 5% of benign non-epithelium-related gastric tumors. We report the case of a 49-year-old woman in whom upper gastrointestinal endoscopy revealed an approximately 2-cm submucosal tumor on the anterior wall of the fornix of the stomach. Contrast-enhanced computed tomography revealed a homogeneously enhanced lesion (~ 17 mm) in the upper third of the stomach as well as a lesion (~ 25 mm) on the left kidney that was strongly enhanced in the early phase. An 18F-fluorodeoxyglucose positron emission tomography scan revealed high accumulation that is characteristic of gastric tumors. The possibility of malignancy was not completely excluded, and the gastric tumor was resected by non-exposed endoscopic wall-inversion surgery. The patient was discharged with a good prognosis 5 days after surgery. In conclusion, non-exposed endoscopic wall-inversion surgery is a minimally invasive and effective method for resecting small gastric submucosal tumors (diameters < 3 cm) for which preoperative diagnosis is difficult.

Esophageal Leiomyosarcoma Diagnosed by Endoscopic Ultrasound-guided Fine-needle Aspiration Biopsy and Cured with Surgical Resection.

Esophageal leiomyosarcomas are rare. We herein present the case of an 82-year-old patient who underwent upper gastrointestinal endoscopy, which revealed a submucosal tumor of 30 mm in diameter that was in contact with the esophagus. Endoscopic ultrasound-guided fine needle aspiration biopsy was performed and the histopathological findings indicated esophageal leiomyosarcoma. Surgical resection was performed. On histopathological examination, the tumor was found to consist of spindle cells with deep chromatin nuclei. The tumor was finally diagnosed as esophageal leiomyosarcoma. We were able to diagnose early-stage esophageal leiomyosarcoma using endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA). EUS-FNA is mostly recommended as a diagnostic tool for esophageal submucosal tumors.

A Small Bowel Ulcer due to Clopidogrel with Cytomegalovirus Enteritis Diagnosed by Capsule and Double-Balloon Endoscopy.

We report the first case of small bowel ulcers due to clopidogrel in a 74-year-old man. He presented with diarrhea and melena after having been taking low-dose aspirin (LDA) and clopidogrel. There was no evidence of bleeding in the stomach, duodenum, or colon. Capsule endoscopy showed multiple ulcers and erosions in the small intestine. Double-balloon endoscopy revealed multiple ulcers throughout the ileum. Examination of the biopsy specimen showed cytomegalovirus infection. His LDA was discontinued and he was prescribed ganciclovir. However, the small bowel ulcers were aggravated. Therefore, clopidogrel was discontinued. The small bowel ulcers subsequently healed completely, forming scars.

A Novel Potassium-Competitive Acid Blocker Improves the Efficacy of Clarithromycin-containing 7-day Triple Therapy against Helicobacter pylori.

BACKGROUND AND AIMS: In Japan, 7-day triple therapy for Helicobacter pylori including clarithromycin (CAM) was approved in 2000. However, antibiotic resistance subsequently reduced this rate to an unacceptable level (70%). Vonoprazan, an orally bioavailable potassium-competitive acid blocker (P-CAB), was approved in Japan in 2014. This could improve eradication rates by increasing the intragastric pH, thus increasing bacterial antibiotic susceptibility. This study compared the efficacy of 7-day triple therapies that included CAM and vonoprazan or proton pump inhibitor (PPI). METHODS: We prospectively analyzed H. pylori eradication rates in 146 patients receiving 7-day triple therapy containing P-CAB (April 2015 to September 2015), and in a retrospective cohort of 1,305 patients who received 7-day triple therapy containing a PPI (April 2011 to September 2015). RESULTS: H. pylori was eradicated in a significantly higher number of P-CAB-treated patients (89.7% [131/146]) than PPI-treated patients (73.9% [965/1305]; p < 0.05). The eradication rates in P-CAB-treated CAM-sensitive and CAM-resistant bacteria were 100% (44/44) and 87.5% (28/32), respectively, which were significantly higher than the corresponding rates in PPI-treated patients (88.0% [22/25] and 53.8% [7/13], p < 0.05). CONCLUSION: P-CAB improved the efficacy of CAM-containing 7-day triple therapy and would be a valuable first-line treatment for H. pylori infection.

The Influence of Snare Size on the Utility and Safety of Cold Snare Polypectomy for the Removal of Colonic Polyps in Japanese Patients.

BACKGROUND: Cold snare polypectomy (CSP) has been recently reported to be useful for the removal of small colonic polyps. However, the relationship between the histologically complete resection rate and snare size used during CSP has not been reported. Our aim was to assess the utility of CSP. METHODS: We analyzed the histologically complete resection rates and the frequency of complications for 175 colon polyps removed by CSP. Moreover, we examined the histologically complete resection rate associated with different snare sizes used during CSP. RESULTS: There was no significant difference in the histologically complete resection rate between endoscopic mucosal resection (EMR) (60.9%) and CSP (53.1%). There were also no significant differences in the frequency of complications including perforation and postoperative bleeding between EMR (perforation: none; postoperative bleeding: two patients) and CSP (perforation: none; postoperative bleeding: none). Histological examination revealed that the complete resection rate of CSP using a short snare (61.6%) was significantly higher than that of CSP using a long snare (44.9%; P < 0.05). There were no significant differences in the frequency of complications between CSP using the short snare and that using the long snare. CONCLUSIONS: CSP is a safe, useful method for the removal of colonic polyps. CSP using the short snare improved the histologically complete resection rates compared to the long snare. Future studies to further assess the utility of CSP are required.

Clinical risk factors for delayed bleeding after endoscopic submucosal dissection for colorectal tumors in Japanese patients.

BACKGROUND: Endoscopic submucosal dissection (ESD) is a curative, standard therapy for colorectal neoplasms. Some studies have investigated the risk factors for perforation during colorectal ESD. However, few studies have assessed the risk factors for delayed bleeding after colorectal ESD. We studied patients undergoing ESD for colorectal epithelial neoplasms to identify the risk factors for post-ESD bleeding. PATIENTS AND METHODS: We studied 124 consecutive patients undergoing ESD for colorectal epithelial neoplasms. To identify risk factors for delayed bleeding post-ESD, recurrent bleeding post-ESD was compared with patient-related and tumor-related factors. RESULTS: Delayed bleeding after ESD occurred in 10 (8.1%) lesions of 124 colorectal tumors, and the median time from the end of ESD to the onset of bleeding was 18.5 h. Delayed bleeding was significantly higher in tumors located in rectums than in colons (P=0.021), and the number of occurrences of arterial bleeding during ESD was significantly higher in the delayed bleeding group than in the nondelayed bleeding group (P=0.002). The procedure time was significantly longer in the delayed bleeding group than in the nondelayed bleeding group (P=0.012). On multivariate logistic regression analysis, tumor location (odds ratio, 10.13; 95% confidence interval, 1.18-87.03; P=0.035) and three or more occurrences of arterial bleeding during ESD (odds ratio, 6.86; 95% confidence interval, 1.13-41.5; P=0.036) were significant independent risk factors for delayed bleeding. CONCLUSION: The presence of lesions in the rectum and three or more arterial bleeding occurrences during ESD were risk factors for post-ESD bleeding. Patients with these risk factors should be followed up carefully after ESD for colorectal epithelial neoplasms.

A case of early gastric cancer arising from gastritis cystica profunda treated by endoscopic submucosal dissection.

Gastritis cystica profunda (GCP) consists of hyperplasia and cystic dilatation of the gastric glands extending into the submucosa. It occurs in the residual stomach post surgery and in the unoperated stomach. GCP is considered a benign lesion, but there is controversy about its malignant potential. We report a case of early gastric cancer arising from GCP treated by endoscopic submucosal dissection (ESD) in a 55-year-old unoperated man. Upper gastrointestinal endoscopy revealed a 15-mm diameter submucosal tumor (SMT) in the upper corpus of the stomach. The surface had angiotelectasia and slight depression covered with normal mucosa. Neither ulceration nor erosion was seen. Narrow-band imaging endoscopy showed no abnormalities suggesting gastric cancer. Endoscopic ultrasonography visualized the internally low-echoic SMT, harboring tiny cystic lesions, mainly within the second and third layers of the gastric wall. The SMT was removed by ESD to avoid retention and allow for comprehensive diagnosis. It was diagnosed as GCP with partial well-differentiated adenocarcinoma without involvement of the lateral and deep margins, lymphatic invasion, vascular invasion and perineural invasion. The gastric epithelium comprised normal mucosa without dysplasia. ESD seems to be useful for the diagnosis of SMT, including GCP harboring gastric cancer, and avoids unnecessary surgical procedures.

A Case of Thrombotic Thrombocytopenia Purpura Associated with Systemic Lupus Erythematosus: Diagnostic Utility of ADAMTS-13 Activity.

Thrombotic thrombocytopenia purpura (TTP) caused by a deficiency in ADAMTS-13 activity is considered to involve a subset of thrombotic microangiopathy (TMA). Although concept of TTP is included under the umbrella of TMA, discrimination of TTP from TMA is occasionally difficult in an autoimmune disorder. Herein, we report a case with TTP associated with systemic lupus erythematosus (SLE). In this case, it was difficult to discriminate TTP from TMA and the measurement of ADAMTS-13 activity was useful for obtaining an accurate diagnosis. SLE patients having thrombocytopenia in complication with anemia should be considered a monitoring of ADAMTS-13 activity even though the patients lacked symptoms of TTP related to the microvascular coagulation.