Efficacy and safety of biosimilar infliximab in bio-naïve patients with Crohn's disease.

BACKGROUND AND STUDY AIMS: The infliximab biosimilar CT-P13 was the first biosimilar drug targeting tumor necrosis factor-α. However, its efficacy and safety in real-world clinical situations have remained insufficient. Therefore, we aimed to verify the efficacy and safety of CT-P13 in bio-naïve patients with Crohn's disease. PATIENTS AND METHODS: This retrospective multicenter study compared the remission rate at week 54 between patients with Crohn's disease who were treated with originator infliximab or CT-P13. Endoscopic and laboratory findings were assessed in both groups. A total of 184 (156 originator and 28 CT-P13) patients were analyzed. Of these, 138 originator users and 19 biosimilar users completed 54-week administration. RESULTS: The clinical remission rates in patients taking originator infliximab of CT-P13 at week 54 were 92.5 % and 100 %, respectively. The endoscopic scores of each group significantly decreased from baseline at week 54 in both groups, and the mucosal healing rate at week 54 was 53 % and 64 %, respectively. Laboratory data including C-reactive protein, serum albumin, and hemoglobin significantly improved from baseline to week 14 and 54 in both groups. Adverse events were observed more frequently in the CT-P13 group (25 % vs. 4.5 %, p = 0.0015), but severe adverse events were rare in both groups. CONCLUSION: The efficacy and safety of CT-P13 were comparable with those of originator infliximab in bio-naïve patients with Crohn's disease evaluated by clinical, endoscopic, and laboratory findings. This study establishes the needed groundwork for the development of a strategy for treatment with biologics in patients with Crohn's disease.

The long-term effect of biologics in patients with ulcerative colitis emerging from a large Japanese cohort.

To gain a better understanding of the effects of biologics, we evaluated clinical outcomes in patients with moderate to severe exacerbations of ulcerative colitis (UC). This retrospective, multicenter study retrieved the entire clinical courses of UC patients who began treatments between 2004 and 2018. All exacerbations and clinical parameters, including treatment details for exacerbations and both remission and re-exacerbation dates, were identified during the observation period. Two different endpoints, the cumulative incidence rates of surgical resection and re-exacerbation, were evaluated separately in moderate to severe exacerbation events. Among 1401 patients, 1626 exacerbation events were determined according to a partial Mayo score (remission: < 2, mild: 2-4, moderate: 5-7, and severe: > 7). During the observation period, as administration rates of biologics increased, both surgical resection and hospitalization rates decreased, for 959 moderate to severe exacerbation events. We confirmed that biologics significantly reduced the cumulative re-exacerbation rate in moderate to severe exacerbation events during the study period compared with suboptimal therapies (a 0.507-fold decreased risk according to COX regression analysis, P < 0.001). However, they had not enough impact in reducing the cumulative incidence rate of surgical resection in moderate to severe exacerbation events that were corticosteroid-refractory or dependent (a 0.878-fold decreased risk according to COX regression analysis, P = 0.606). Biologics may improve remission duration, but these agents had no significant impact in reducing the risk of surgical resection in moderate to severe active UC.

Berberine for prevention of dementia associated with diabetes and its comorbidities: A systematic review.

BACKGROUND: A growing number of epidemiological studies indicate that metabolic syndrome (MetS) and its associated features play a key role in the development of certain degenerative brain disorders, including Alzheimer's disease and vascular dementia. Produced by several different medicinal plants, berberine is a bioactive alkaloid with a wide range of pharmacological effects, including antidiabetic effects. However, it is not clear whether berberine could prevent the development of dementia in association with diabetes. OBJECTIVE: To give an overview of the therapeutic potential of berberine as a treatment for dementia associated with diabetes. SEARCH STRATEGY: Database searches A and B were conducted using PubMed and ScienceDirect. In search A, studies on berberine's antidementia activities were identified using "berberine" and "dementia" as search terms. In search B, recent studies on berberine's effects on diabetes were surveyed using "berberine" and "diabetes" as search terms. INCLUSION CRITERIA: Clinical and preclinical studies that investigated berberine's effects associated with MetS and cognitive dysfunction were included. DATA EXTRACTION AND ANALYSIS: Data from studies were extracted by one author, and checked by a second; quality assessments were performed independently by two authors. RESULTS: In search A, 61 articles were identified, and 22 original research articles were selected. In search B, 458 articles were identified, of which 101 were deemed relevant and selected. Three duplicates were removed, and a total of 120 articles were reviewed for this study. The results demonstrate that berberine exerts beneficial effects directly in the brain: enhancing cholinergic neurotransmission, improving cerebral blood flow, protecting neurons from inflammation, limiting hyperphosphorylation of tau and facilitating ß-amyloid peptide clearance. In addition, evidence is growing that berberine is effective against diabetes and associated disorders, such as atherosclerosis, cardiomyopathy, hypertension, hepatic steatosis, diabetic nephropathy, gut dysbiosis, retinopathy and neuropathy, suggesting indirect benefits for the prevention of dementia. CONCLUSION: Berberine could impede the development of dementia via multiple mechanisms: preventing brain damages and enhancing cognition directly in the brain, and indirectly through alleviating risk factors such as metabolic dysfunction, and cardiovascular, kidney and liver diseases. This study provided evidence to support the value of berberine in the prevention of dementia associated with MetS.

Anti-MAdCAM-1 antibody (PF-00547659) for active refractory Crohn's disease in Japanese and Korean patients: the OPERA study.

BACKGROUND/AIMS: PF-00547659 is a monoclonal antibody against human mucosal addressin cell adhesion molecule-1 (MAdCAM-1) that prevents the binding of α4ß7+ lymphocytes to MAdCAM-expressing sites in the gastrointestinal tract with high affinity and selectivity, and is being developed for the treatment of Crohn's disease (CD). METHODS: OPERA is a randomized, multicenter, double-blind, placebo-controlled study to investigate the efficacy, safety, and pharmacokinetics of PF-00547659 following subcutaneous administration in subjects with active CD, a history of failure or intolerance to anti-tumor necrosis factor and/or immunosuppressants, high-sensitivity C-reactive protein > 3.0 mg/L, and ulcers on colonoscopy. The primary endpoint was Crohn's Disease Activity Index-70 response at week 8 or 12. Subpopulation analyses for Asian subjects were performed as some differences are observed in genetics and clinical phenotypes in Asian CD patients compared with Western patients. RESULTS: In this study, 265 CD subjects were randomized, with a subpopulation of 21 subjects (8 Japanese and 13 Korean) defined as the Asian population. In the overall and Asian populations; PF-00547659 was pharmacologically active as evidenced by soluble MAdCAM and circulating ß7+ central memory CD4+ T-lymphocytes, although no clear evidence of efficacy was observed in any clinical endpoints; pharmacokinetics of PF-00547659 in the Asian subpopulation was generally comparable to the overall population; and the safety profile of PF-00547659 appeared acceptable up to 12 weeks of treatment. CONCLUSIONS: In the overall and Asian populations, efficacy of PF-00547659 could not be demonstrated using any clinical endpoints compared with placebo. Pharmacokinetics and safety of PF-00547659 were generally comparable. Further studies with larger numbers of patients are required to confirm our results. (Trial Registration Number: NCT01276509).

Renal Dysfunction is a Risk Factor of Death after Gastric Endoscopic Submucosal Dissection in Elderly Patients Aged ≥80 Years.

Introduction: Endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) is well accepted. However, its adaptation for elderly patients is unclear. This study aimed to investigate the prognosis and long-term outcomes of ESD for EGC in elderly patients aged ≥80 years by comparing their findings to the findings of patients aged <80 years. Materials and Methods: The study included 533 patients (632 lesions). The patients were divided into an elderly group (age, ≥80 years; 108 patients; 128 lesions; mean age, 83.4 ± 2.7 years) and a nonelderly group (age, <80 years; 425 patients; 504 lesions; mean age, 69.6 ± 7.9 years). We compared patient and lesion characteristics, overall survival (OS), and disease-specific survival (DSS) between the 2 groups retrospectively. Multivariate analysis was performed to clarify the risk factors of death after ESD. Results: The rate of curative resection and adverse events was not significantly different between the groups. The mean survival time periods with regard to OS/DSS in the elderly and nonelderly groups were 75.8 ± 5.9 and 122.8 ± 2.6 months (P < 0.05)/120.0 ± 3.0 and 136.4 ± 0.6 months (not significant), respectively. In the elderly group, eGFR <30 ml/min/1.73 m2 was an independent risk factor of death (hazard ratio = 5.32; 95% confidence interval = 1.39-20.5; P=0.015). Conclusion: ESD for EGC can be performed safely and can achieve high curability with good prognosis in elderly patients aged ≥80 years. After ESD, close attention should be paid to elderly patients with severe chronic kidney disease.

Immunomodulator-associated Epstein-Barr virus-positive mucocutaneous ulcer in a patient with refractory Crohn's disease.

Epstein-Barr virus (EBV)-positive mucocutaneous ulcer is a B-cell lymphoproliferative disorder occurring in elderly or iatrogenic immunocompromised patients. We report a 27-year-old male patient with Crohn's disease (CD) who developed immunomodulator-associated lymphoproliferative disorder. The patient was diagnosed with CD at the age of 17 and was treated with maintenance therapy including high-dose infliximab and azathioprine. When he was admitted to our hospital with a diagnosis of intestinal obstruction, his abdominal computed tomography findings showed not only colonic wall thickening and narrowing of the descending colon but also multiple liver tumor lesions. His ileus symptom improved with conservative therapy, and a pathological evaluation of the tissue biopsy specimens from the descending colon and liver lesions indicated a morphological diagnosis of EBV-positive diffuse large B-cell lymphoma. This was a case of iatrogenic immunodeficiency-associated lymphoproliferative disorder due to an immunomodulator. The treatment was initiated with chemotherapy, but he died of disease progression 10 months after the diagnosis of lymphoma. Although cases of lymphoproliferative disorder due to treatment modalities used for CD are rare in Japan, an increase in the risk of lymphoproliferative diseases should be considered in patients with CD treated with immunomodulatory agents.

Long-Term Prognosis of Patients with Obscure Gastrointestinal Bleeding: A Retrospective Cohort Study.

AIMS: We evaluated the long-term prognosis of patients with obscure gastrointestinal bleeding (OGIB) who underwent capsule endoscopy (CE). METHODS: In our hospital, 429 patients underwent CE between November 2007 and March 2012. Among them, 259 patients underwent CE as the first examination for OGIB and were then followed at 77 clinics and hospitals. The clinical characteristics were investigated, including age, gender, overt/occult bleeding, the use of antithrombotic drugs and NSAIDs, complications (liver cirrhosis and hemodialysis), and CE. We asked the medical institutions for their survival data as of August 2017 (> 5 years after CE). RESULTS: The prognoses of 240 patients (92.6%) were analyzed. The average follow-up period was 55.7 (1-115) months. During the follow-up period, 57 patients (23.8%) died and the survival rates were 90.5% at 1 year, 81.7% at 3 years, and 74.7% at 5 years. Age 65 years or older and liver cirrhosis were predictive factors for a poor prognosis. Rebleeding occurred in 42 patients (17.9%) and small bowel cancer and gastrointestinal stromal tumor were found at 12 and 21 months after CE, respectively. CONCLUSIONS: Patients with OGIB showed a poor prognosis, especially those who were elderly or who had liver cirrhosis.

Comparison of a novel predictor of venous thromboembolic complications in inflammatory bowel disease with current predictors.

BACKGROUND AND AIM: Venous thromboembolism (VTE) is a common complication of inflammatory bowel disease (IBD). The aim of the present study was to identify predictors of VTE in hospitalized patients with IBD. METHODS: Patients with IBD who were hospitalized from February 2015 to March 2016 at the Chiba University Hospital were included. VTE was detected using enhanced computed tomography, and VTE onset within 2 months after admission was assessed. Predictors of VTE onset were investigated with clinical factors during hospitalization. Availability of the Caprini risk assessment model and Padua prediction score at the time of admission was also assessed. RESULTS: Seventy-two patients with IBD were hospitalized, and central venous catheters were placed in 43 of the 72 patients. During the observation period, VTE occurred in six patients (8.3%); however, none died as a result of the condition. Cox proportional hazards regression analysis identified D-dimer values on admission as a risk factor that was highly associated with VTE onset (hazard ratio = 1.590; 95% confidence interval, 1.132-2.233; P = 0.007) and significantly predicted the occurrence of VTE using the receiver operating characteristic curve (P = 0.005, area under the curve = 0.893). However, Caprini risk assessment model and Padua prediction scores were not useful tools for predicting VTE onset in patients with IBD. CONCLUSION: In hospitalized patients with IBD, D-dimer values were highly associated with VTE onset. Therefore, measurement of D-dimer values on admission is critical for the management of thromboembolic complications in patients with IBD.

Clinical characteristics and outcomes of primary sclerosing cholangitis and ulcerative colitis in Japanese patients.

BACKGROUND: In Western countries, most patients with primary sclerosing cholangitis (PSC) have concurrent ulcerative colitis (UC). The number of patients with UC in East Asia has increased markedly over the past two decades. However, current clinical features of PSC and of PSC associated with UC (PSC-UC) have not yet been clarified in East Asia, particularly in Japan. We aimed to reveal the clinical courses and associations with UC in Japanese patients with PSC from the mutual viewpoint of PSC and UC. METHODS: We retrospectively retrieved medical records of patients with PSC (69) and UC (1242) who were diagnosed at Chiba University Hospital between June 1991 and August 2017. RESULTS: In the present cohort, 37 patients had PSC-UC; the cumulative risks of PSC in patients with UC and of UC in patients with PSC were 3.0% and 53.6%, respectively. We confirmed similar distinctive results by a Japanese nationwide survey, noting that younger patients with PSC had a notably high possibility of association with UC. From the viewpoint of the UC cohort, the occurrence of right-sided disease was significantly higher in patients with PSC-UC than in those with UC (16.2% vs. 4.2%, P = 0.003). Pancolitis was more commonly observed in PSC-UC, and proctits/left-sided colitis was less commonly found in patients with UC. The number of patients with young-onset PSC-UC may be increasing similar to an increase in patients with UC in Japan. CONCLUSIONS: In our cohort, the comorbidity rate of PSC-UC was higher than that obtained in previous reports. The incidence of PSC-UC and UC may increase in the future in East Asia, particularly in Japan.

Investigation of novel biomarkers for predicting the clinical course in patients with ulcerative colitis.

BACKGROUND: The clinical course of ulcerative colitis (UC) is characterized by repeated episodes of relapse and remission. We hypothesized that biomarkers that help distinguish refractory UC patients who are in remission using strong anti-immunotherapy could contribute in preventing the overuse of corticosteroids for treatment. Here, we clarified novel autoantibodies for UC patients in remission as clinical indicators to distinguish between refractory and non-refractory UC. METHODS: Antigen proteins recognized by serum antibodies of patients with UC in remission were screened using the protein array method. To validate the results, AlphaLISA was used to analyze the serum antibody titers with candidate protein antigens. Serum samples from 101 healthy controls, 121 patients with UC, and 39 patients with Crohn's disease were analyzed. RESULTS: Of 66 candidate protein antigens screened by ProtoArray™, six were selected for this study. The serum titers of anti-poly ADP-ribose glycohydrolase (PARG), anti-transcription elongation factor A protein-like 1, and anti-proline-rich 13 (PRR13) antibodies were significantly higher in patients with UC than in healthy controls. Anti-PARG and anti-PRR13 antibody titers were significantly higher in patients with refractory UC than in patients with non-refractory UC. There were no significant differences in any antibody titer between the active and remission phases. CONCLUSIONS: The serum titers of anti-PARG, anti-transcription elongation factor A protein-like 1, and anti-PRR13 antibodies were elevated in patients with UC. Anti-PARG and anti-PRR13 antibody titers may be novel clinical indicators for detecting refractory UC in patients in remission.

Real-time Endoscopy-Guided Measurement of Rectal Mucosal Admittance Is a Novel and Safe Method for Predicting Ulcerative Colitis Relapse.

Background: There are known associations between inflammatory bowel disease (IBD) and changes in mucosal paracellular permeability. We recently developed a novel catheter that can measure mucosal admittance (MA). Methods: Patients with ulcerative colitis (UC) in clinical remission underwent real-time MA measurement during colonoscopy between June 2014 and July 2015 and were prospectively followed. MA measures were taken from normal-appearing mucosa using the Tissue Conductance Meter (TCM). We examined relationships between mucosal admittance, clinical parameters at the time of MA measurement, and disease relapse during the follow-up period using the Cox proportional hazards model. Results: We measured baseline MA in 54 patients with UC during remission, with no complications. Of these, 23 patients relapsed during the subsequent follow-up period, at a median of 25.8 ± 7.6 months. Rectal MA was the only predictor of disease relapse in multivariate analysis (P = 0.027). The optimal rectal MA cutoff value for relapse was 781.0 (area under the receiver operating characteristic curve, 0.712), and in patients who showed lower than normal cutoff values, there was a significantly higher likelihood of relapse compared with other patients (log-rank test, P < 0.001). Conclusions: High rectal MA measured by TCM is associated with long-term sustained remission. Real-time rectal MA measurement using a novel endoscopy-guided catheter could be a safe and useful means of predicting prognosis for patients with UC in remission.

Long-Term Outcome of Endoscopic Balloon Dilatation for Strictures in Patients with Crohn's Disease.

BACKGROUND/AIMS: Endoscopic balloon dilatation (EBD) is an alternative to surgery for strictures in patients with Crohn's disease (CD). The aim of the present study was to clarify the efficacy and safety of EBD for strictures in patients with CD. METHODS: Twenty-six patients with CD who underwent EBD for strictures from August 2008 to November 2015 were followed up after dilatation. Short-term success was defined as the disappearance of obstructive symptoms after technically adequate dilatation was achieved. The short-term success rate of EBD, safety profile of EBD, and cumulative surgery-free and redilatation-free rates were analyzed. RESULTS: Sixty-five EBDs were performed for CD patients in the follow-up period. The short-term success rate was 100% (26/26), and no complications were encountered during this study. Two (7.7%) patients underwent surgery during the observation period. The cumulative surgery-free rate after the initial EBD was 90.3% at both 2 and 3 years. The cumulative redilatation-free rate after the initial EBD was 52.1% at 2 years and 39.1% at 3 years. CONCLUSION: EBD for strictures secondary to CD provides not only short-term success but also long-term efficacy. Although a high redilatation rate is one of the clinical problems of this procedure, EBD is an effective therapy for avoiding intestinal recession in CD -stricture.

Residual adenoma after cold snare polypectomy for small colorectal adenomas: a prospective clinical study.

BACKGROUND: Endoscopic resection of all colonic adenomas prevents the occurrence of colon cancer and death. The European Society of Gastrointestinal Endoscopy Clinical Guideline recommends resection of all polyps predicted to be adenomas and cold snare polypectomy (CSP) for removal of adenomas ≤ 9 mm on the basis of safety; however, it also states that this recommendation lacks adequate evidence of efficacy. The residual adenoma rate after resection is an important indicator of efficacy, but there have been no reports showing this prospectively. Therefore, we aimed to investigate the residual adenoma rate after CSP of small colonic polyps. METHODS: Between March 2015 and April 2017, patients who were endoscopically diagnosed with colorectal adenomas < 9 mm underwent CSP, the site being marked with endoscopic clips. Patients with pathologically confirmed adenomas underwent follow-up colonoscopy 3 weeks after CSP and any post-CSP scars were biopsied. The primary endpoint was the presence of pathological residual adenoma 3 weeks after CSP. RESULTS: Overall, 126 lesions in 39 patients were removed and 125 (99.2 %) were resected en bloc using CSP. Pathologically, 111 lesions (88.1 %) were confirmed as adenomas (4.2 ± 1.5 mm), with 36 of these (32.4 %) determined to be R0 resections. No complications were observed. All 37 patients with pathologically confirmed adenomas underwent follow-up colonoscopy, and 102 of 111 scars were detected in 33 patients. One pathological residual adenoma (0.98 %, 95 % confidence interval 0.02 % - 5.3 %) was identified. CONCLUSIONS: CSP appears to be an effective treatment for diminutive and small colorectal adenomas, with a low residual adenoma rate.

Development of intestinal M cells and follicle-associated epithelium is regulated by TRAF6-mediated NF-κB signaling.

M cells are located in the follicle-associated epithelium (FAE) that covers Peyer's patches (PPs) and are responsible for the uptake of intestinal antigens. The differentiation of M cells is initiated by receptor activator of NF-κB. However, the intracellular pathways involved in M cell differentiation are still elusive. In this study, we demonstrate that the NF-κB pathway activated by RANK is essential for M cell differentiation using in vitro organoid culture. Overexpression of NF-κB transcription factors enhances the expression of M cell-associated molecules but is not sufficient to complete M cell differentiation. Furthermore, we evaluated the requirement for tumor necrosis factor receptor-associated factor 6 (TRAF6). Conditional deletion of TRAF6 in the intestinal epithelium causes a complete loss of M cells in PPs, resulting in impaired antigen uptake into PPs. In addition, the expression of FAE-associated genes is almost silenced in TRAF6-deficient mice. This study thus demonstrates the crucial role of TRAF6-mediated NF-κB signaling in the development of M cells and FAE.

A Prospective Study of Eosinophilic Esophagitis and the Expression of Tight Junction Proteins in Patients with Gastroesophageal Reflux Disease Symptoms.

BACKGROUND/AIMS: Eosinophilic esophagitis (EoE) is often erroneously diagnosed as gastroesophageal reflux disease (GERD). The aim of this study is to investigate the prevalence of EoE and the expression of tight junction (TJ) proteins in patients with GERD symptoms. METHODS: One hundred patients with GERD symptoms and 10 healthy controls were prospectively studied. Sixty-two patients had symptoms refractory to proton pump inhibitors (PPI). All patients underwent esophageal biopsy. Patients were diagnosed with EoE if the number of eosinophil granulocytes per high-power field was ≥15. Immunohistochemical analysis of TJ proteins (claudin-1, claudin-4, occludin, and zonula occludin-1 [ZO-1]) was performed. RESULTS: EoE was diagnosed in six of 100 patients (6%) with GERD symptoms and in six patients (9.7%) of 62 patients with PPI-refractory GERD. Only one had typical EoE endoscopic findings. The proportion of ZO-1-positive cells was significantly lower in the lower than in the middle esophagus (56.0%±14.0% vs 66.0%±11.5%, p＜0.05). There were no significant correlations between TJ protein expression and GERD symptoms. CONCLUSIONS: The prevalence of EoE among patients with PPI-refractory GERD is approximately 10%. Regardless of endoscopic findings, esophageal biopsy is crucial in diagnosing EoE. The disruption of ZO-1 expression in the lower esophagus is significantly associated with GERD symptoms.

Endoscopic-Guided Measurement of Mucosal Admittance can Discriminate Gastroesophageal Reflux Disease from Functional Heartburn.

OBJECTIVES: A novel catheter that can measure mucosal admittance (MA), the inverse of impedance, was developed recently. In this pilot study, we aimed to clarify the usefulness of measuring MA for diagnosing gastroesophageal reflux disease (GERD). METHODS: We conducted two prospective studies. In the first study, esophageal MA was evaluated in 120 participants (24 with erosive esophagitis, 82 with heartburn but non-erosive esophagitis, and 14 healthy volunteers) and compared with the endoscopic findings. In the second study, multichannel intraluminal impedance combined with pH (MII-pH) tests was conducted followed by an MA measurement in 33 patients with non-erosive esophagitis and proton pump inhibitor (PPI)-refractory heartburn. Based on the MII-pH test results, patients were divided into GERD or functional heartburn (FH). MA was compared between the GERD and FH groups and also compared with the baseline impedance (BI) and acid exposure time (AET). RESULTS: Median MA at the distal esophagus was significantly higher in patients with erosive esophagitis compared with that in patients with non-erosive esophagitis and healthy volunteers (46.8, 13.1 and 6.5, respectively, P<0.01). In patients with PPI-refractory heartburn, the median MA at the distal esophagus was significantly higher in patients with GERD than those with FH (19.3 vs. 7.2, P<0.05). There was a negative correlation between MA and BI, and a positive correlation between MA and AET at the distal esophagus (r=-0.46 and r=0.53, P<0.05). CONCLUSIONS: Real-time measurement of MA is useful to distinguish GERD from non-GERD.

Cold polypectomy for duodenal adenomas: a prospective clinical trial.

Background and study aims Endoscopic resection is effective in treating nonampullary duodenal adenomas but has a high incidence of complications. Cold polypectomy, including cold forceps polypectomy (CFP) and cold snare polypectomy (CSP), is safe and effective in treating colorectal polyps. However, its utility in sporadic nonampullary duodenal adenomas has not been investigated. The purpose of this prospective study was to examine the safety and efficacy of cold polypectomy for sporadic nonampullary duodenal adenomas. Patients and methods Between March 2015 and June 2016, patients who were endoscopically diagnosed with sporadic nonampullary duodenal adenomas up to 6 mm underwent cold polypectomy. Patients with pathologically confirmed adenomas underwent endoscopic biopsy 3 months after resection. The main outcomes of interest were incomplete resection and complications. Results Overall, 39 lesions in 30 patients were removed via cold polypectomy (CFP, 9 lesions in 8 patients; CSP, 30 lesions in 22 patients). Seven of 9 (77.8 %) and 29 of 30 (96.7 %) lesions were removed en bloc via CFP and CSP, respectively. Pathologically, 34 of the 39 lesions (87.2 %) were confirmed as adenomas, and their mean size was 3.9 ±â€Š1.2 mm (range 2 - 6 mm). Of the 34 adenomas, 20 (58.8 %) were R0 resection lesions, of which 3 of 9 (33.3 %) and 17 of 25 (68.0 %) had undergone CFP and CSP, respectively. No delayed bleeding or intraprocedural/delayed perforation was observed. All 30 patients with the 34 pathologically confirmed adenomas underwent upper gastrointestinal endoscopy 3 months after cold polypectomy, and no morphological or pathological recurrence was identified. Conclusions In this small study, cold polypectomy appeared to be safe and effective in treating diminutive and small sporadic nonampullary duodenal adenomas.(Clinical trial registration number: UMIN000016829).

Endoscopy-Guided Evaluation of Duodenal Mucosal Permeability in Functional Dyspepsia.

OBJECTIVES: The pathophysiology of functional dyspepsia (FD) is not fully understood. Impaired duodenal mucosal integrity characterized by increased mucosal permeability and/or low-grade inflammation was reported as potentially important etiologies. We aimed to determine the utility of a recently developed simple catheterization method to measure mucosal admittance (MA), the inverse of mucosal impedance, for evaluation of duodenal mucosal permeability in patients with FD. METHODS: We conducted two prospective studies. In the first study, duodenal MA of 23 subjects was determined by catheterization during upper endoscopy, and transepithelial electrical resistance (TEER) of duodenal biopsy samples in Ussing chambers was measured to assess the correlation between MA and TEER. In the second study, duodenal MA of 21 patients with FD fulfilling the Rome III criteria was compared with that of 23 healthy subjects. RESULTS: The mean MA and TEER values were 367.5±134.7 and 24.5±3.7 Ω cm2, respectively. There was a significant negative correlation between MA and TEER (r=-0.67, P=0.0004, Pearson's correlation coefficient). The mean MA in patients with FD was significantly higher than that in healthy subjects (455.7±137.3 vs. 352.1±66.9, P=0.002, unpaired t-test). No procedure-related complications were present. CONCLUSIONS: We demonstrated the presence of increased duodenal mucosal permeability in patients with FD by MA measurement using a simple catheterization method during upper endoscopy.

The Effect of Ineffective Esophageal Motility on Gastroesophageal Reflux Disease.

BACKGROUND/AIMS: Ineffective esophageal motility (IEM) is the most common gastrointestinal motility disorder. Studies have reported that IEM is related to gastroesophageal reflux disease (GERD). However, the relationship between IEM and GERD remains uncertain. This study aims to clarify this relationship retrospectively. METHODS: We analyzed 195 subjects who underwent high-resolution manometry between January 2011 and September 2016. Of these subjects, 72 had normal esophageal motility (NEM) and 26 had IEM. We investigated differences in the clinical characteristics, severity and duration of GERD symptoms, and comorbid extra-esophageal symptoms of the subjects. Comorbid extra-esophageal symptoms were assessed with the Gastrointestinal Symptom Rating Scale questionnaire. Investigation-defined GERD was diagnosed when erosive esophagitis or abnormal multichannel intraluminal impedance was present. RESULTS: We found no significant difference in the prevalence of IEM between patients with and without GERD (37.5 and 21.1%, respectively; p = 0.174). There were no differences in age, gender, body mass index, presence of hiatal hernia, or duration of GERD between the groups. Compared to patients with NEM, those with IEM were significantly less likely to have comorbid extra-esophageal symptoms (p < 0.05). CONCLUSION: There is no association between IEM and GERD.

Mesenteric findings of CT enterography are well correlated with the endoscopic severity of Crohn's disease.

BACKGROUND: Maintenance of mucosal healing is a primary goal when treating Crohn's disease (CD). Endoscopy is the most precise method for the assessment of mucosal healing, but is considered overly invasive for patients with CD. In contrast, CT enterography (CTE) is less invasive, but little is known about the correlation between mucosal status and CTE parameters. METHODS: We recruited CD patients who underwent CTE and double balloon endoscopy (DBE) on the same day at our hospital between 2012 and 2014. CTE parameters evaluated included bowel-wall thickening, mural hyperenhancement, mural stratification (target sign), submucosal fat deposition, mesenteric hypervascularity (comb sign), increased fat density, mesenteric fibrofatty proliferation, enlarged mesenteric lymph nodes, and stenosis/sacculation. Endoscopic findings were evaluated using the Simple Endoscopic Score for Crohn's Disease (SES-CD). CTE parameters that were predictive of higher values in the SES-CD were extracted statistically. RESULTS: Forty-one patients were recruited, from which 191 intestinal segments were evaluated. Spearman's rank correlation coefficients showed that the majority of CTE values exhibited mild to moderate correlations with SES-CD values. Notably, multiple ordinal logistic regression analysis demonstrated that CTE findings obtained from the mesenteric area, such as mesenteric hypervascularity (comb sign) and enlarged mesenteric lymph nodes, were more critical predictors of endoscopic mucosal ulceration than those obtained from the bowel wall. CONCLUSIONS: This study was the first of its kind to assess correlations between CTE values and SES-CD values. Mesenteric findings of CTE, rather than mural findings, were highly correlated with the endoscopically evaluated severity of ulceration.