Risk factors for postgastric endoscopic submucosal dissection bleeding in direct oral anticoagulant users.

OBJECTIVES: Bleeding after endoscopic submucosal dissection (ESD) for gastric tumors in patients taking antithrombotic drugs, in particular direct oral anticoagulants (DOACs), remains unresolved; therefore, we evaluated the risk factors for post-ESD bleeding and drug differences in patients taking DOACs. METHODS: We included 278 patients taking antithrombotic drugs who underwent gastric ESD between January 2017 and March 2022. Antithrombotic drugs were withdrawn following the 2017 guidelines (Appendix on anticoagulants including DOACs). To further clarify differences in antithrombotic agents' effects, the peri-cancerous mucosa in the resected specimen was pathologically evaluated according to the Updated Sydney System. Multivariate analysis was performed to assess the risk of post-ESD bleeding. RESULTS: The incidence of post-ESD bleeding in patients taking DOACs was 19.6% (10/51). Among patients taking antithrombotic drugs, DOACs were identified as a possible factor involved in post-ESD bleeding (odds ratio [OR] 4.92). Among patients taking DOACs, possible factors included resection length diameter ≥30 mm (OR 3.72), presence of neutrophil infiltration (OR 2.71), lesions occurring in the lower third of stomach (OR 2.34), and preoperative antiplatelet use (OR 2.22). Post-ESD bleeding by DOAC type was 25.0% of patients (4/16) receiving apixaban, in 20.0% (3/15) receiving edoxaban, in 21.4% (3/14) receiving rivaroxaban, and in none of those receiving dabigatran. CONCLUSIONS: The administration of DOACs was shown to be a possible factor involved in post-ESD bleeding, and risk factors for patients taking DOACs included neutrophil infiltration. The pharmacological differences in the effects of DOACs contributing to bleeding in gastric ulcers suggest comparatively less bleeding with dabigatran after ESD.

[Cystic duct carcinoma in a patient with a history of cholecystectomy: a case report].

An 83-year-old Japanese man who underwent cholecystectomy for cholecystolithiasis 17 years ago visited our hospital owing to epigastric pain. He was initially diagnosed with choledocholithiasis and acute cholangitis following white blood cell, C-reactive protein, total bilirubin, alkaline phosphatase, and γ-glutamyltranspeptidase level elevations along with common bile duct stones on computed tomography (CT). Moreover, CT, magnetic resonance imaging, endoscopic retrograde cholangiography (ERC), and endoscopic ultrasonography (EUS) also revealed a 2-cm-diameter mass arising from the remnant cystic duct. The cytology of the bile at the time of ERC was not conclusive. However, EUS-assisted fine needle aspiration (EUS-FNA) of the mass confirmed the diagnosis of adenocarcinoma of the remnant cystic duct. The patient underwent extrahepatic bile duct resection. Cystic duct carcinoma following cholecystectomy is rare. We report a case diagnosed by EUS-FNA.

Dasatinib-induced colitis: clinical, endoscopic and histological findings.

BACKGROUND: Dasatinib, a second-generation tyrosine kinase inhibitor, is widely used in patients with haematological malignancies. The main side effects of dasatinib are myelosuppression and pleural effusion; however, colitis, such as haemorrhagic colitis and cytomegalovirus (CMV) colitis, have been reported as rare side effects. There are only a few studies conducted on dasatinib-induced colitis. AIMS: This study aimed to clarify the clinical, endoscopic and pathological features of dasatinib-induced colitis. METHODS: This retrospective study included 51 consecutive patients who received dasatinib therapy between June 2009 and July 2020. Dasatinib-induced colitis was defined as the presence of colitis symptoms, exclusion of other diseases that could cause colitis, and improvement in symptoms after dasatinib withdrawal or dose reduction. CMV positivity was determined based on the positive result of CMV immunostaining. RESULTS: Dasatinib-induced colitis was diagnosed in nine of 51 patients (17.6%), and most of the symptoms were mild diarrhoea and bloody stools. The endoscopic findings were characterised by loss of vascular pattern (100%) and multiple small erosions (83.3%) which were mainly found in the transverse and descending colon. In a patient who underwent follow-up colonoscopy once a year while taking dasatinib, endoscopic findings changed from initial erythematous spots to multiple erosions, and finally to multiple small round elevations with erosion on the top that disappeared after discontinuation of dasatinib. Anti-CMV therapy was administered to one patient, but the treatment failed. All patients with dasatinib-induced colitis were cured after the discontinuation of dasatinib. CONCLUSION: Physicians should consider CMV reactivation to manage dasatinib-induced colitis.

Anti-proteinase 3 antineutrophil cytoplasmic antibody reflects disease activity and predicts the response to steroid therapy in ulcerative colitis.

BACKGROUND: Serum anti-proteinase 3 antineutrophil cytoplasmic antibody (PR3-ANCA) is a disease-specific antibody against granulomatosis with polyangiitis. PR3-ANCA is a useful serological marker for disease severity in ulcerative colitis (UC). The purpose of this study was to investigate whether PR3-ANCA levels could also predict the success of induction therapy and to compare its performance against other markers, including serum CRP and fecal hemoglobin. METHODS: This was a multicenter retrospective study. In total, 159 patients with active-phase UC underwent colonoscopy. Disease activity was measured using the Mayo endoscopic subscore (MES). PR3-ANCA positivity and the response to induction therapy, either 5-aminosalicylic acid or steroid, were assessed. PR3-ANCA, CRP, and fecal hemoglobin were measured during the active phase, and during clinical remission. RESULTS: Eighty-five (53.5%) of 159 patients with active UC were positive for PR3-ANCA. PR3-ANCA titers were significantly higher in the group of patients with MES 3 compared to patients with MES 1 (P = 0.002) or MES 2 (P = 0.035). Steroid therapy was administered to 56 patients with a median partial Mayo score of 7 (5-9), which is equivalent to moderate-to-severe disease activity. PR3-ANCA positivity of non-responders to steroid therapy was significantly higher than that of responders (71.9% vs, 41.7%, P = 0.030), whereas CRP and fecal hemoglobin were not predictive of steroid response. Multivariate analysis demonstrated that PR3-ANCA positivity was associated with non-response to steroid therapy (odds ratio 5.19; 95% confidence interval, 1.54-17.5; P = 0.008). Of the 37 patients treated to clinical remission who were also positive for PR3-ANCA during the active phase, 27 had an MES of ≥ 1, and 10 patients had an MES of 0. In clinical remission, the proportion of patients with MES 0 in 17 patients whose PR3-ANCA became negative was significantly higher than that in 20 patients whose PR3-ANCA remained positive (47.1% vs. 10.0%, P = 0.023). CONCLUSIONS: PR3-ANCA not only serves as a marker of disease activity, but also predicts the failure of steroid therapy in moderate-to-severe UC. TRIAL REGISTRATION: This study was retrospectively registered in the UMIN Clinical Trials Registry System (000039174) on January 16, 2020.

[A case report of Legionella pneumonia in a patient with ulcerative colitis undergoing remission maintenance using azathioprine].

A 67-year-old man was diagnosed with ulcerative colitis one year ago. Remission was induced via the oral administration of prednisolone and azathioprine;prednisolone was gradually reduced and discontinued. He maintained remission with azathioprine but developed fever and general malaise and visited the Kagawa Prefectural Central Hospital. Chest radiography and a urinary antigen test revealed Legionella pneumonia. His symptoms reduced immediately after the initiation of levofloxacin. Azathioprine suppresses cellular immunity and may increase the risk of Legionella pneumonia.

Long-term outcomes of patients with Crohn's disease who received infliximab or adalimumab as the first-line biologics.

BACKGROUND AND AIM: Although previous studies compared the efficacy of infliximab (IFX) versus adalimumab (ADA) as the first-line biologics for Crohn's disease (CD), the difference in long-term prognosis based on which biologic was used first has scarcely been reported. In particular, the clinical courses after loss of response (LOR) of the first-line biologics are largely unknown. METHODS: A multicenter, retrospective study was performed. Disease courses of biologic-naïve CD patients who were started on IFX or ADA treatment were evaluated, even after LOR of the initial biologics. RESULTS: In total, 263 CD patients were eligible for analysis, 183 were treated with IFX first, and 80 were treated with ADA first. The median observation period was 64.2 months. The cumulative steroid-free remission rates and surgery-free rates did not differ significantly between the patients treated with IFX first and those treated with ADA first (log-rank test P = 0.42 and P = 0.74, respectively). In addition, no significant difference was observed in the rate of occurrence of events associated with ineffectiveness (modification of anti-tumor necrosis factor treatment including intensification, switch, discontinuation, or surgery) between the patient groups (log-rank test P = 0.62). The patients treated with IFX first were likely to discontinue the agent due to adverse events, whereas those treated with ADA first were likely to discontinue due to treatment failure or LOR. CONCLUSIONS: No significant difference was observed in the long-term prognosis between biologic-naïve patients with CD who were started treatment with IFX first and ADA first.

[A case of small intestinal ulcer caused by non-steroidal anti-inflammatory drugs patch].

A ring-shaped ulcer was observed in the ileum of a 70-year-old male patient with capsule endoscopy of the small intestine performed for detailed investigation of black stools and iron deficiency anemia. Non-steroidal anti-inflammatory drugs (NSAIDs) use in patch form was considered as the etiology. The NSAIDs patches were discontinued, and protective therapy for small intestinal mucosa was initiated. The anemia improved;however, ileus originating from the site of the ulcer required surgical resection. The resected specimen showed no specific pathological findings. Based on the clinical findings, the patient was diagnosed with NSAIDs-induced small intestinal ulcer. The use of NSAIDs patches should be considered as a potential cause of injury to gastrointestinal mucosa.

Bleeding in patients who underwent scheduled second-look endoscopy 5 days after endoscopic submucosal dissection for gastric lesions.

BACKGROUND: Bleeding after endoscopic submucosal dissection (ESD) in antithrombotic drug users is still one of the important issues to be solved. We performed scheduled second-look endoscopy (SLE) 5 days after ESD, when the resumption of antithrombotic agents is assumed to have achieved a steady state, rather than on the day after ESD. We investigated bleeding incidence and the status of ulcers. METHODS: A total of 299 lesions in 299 patients subjected to ESD for gastric neoplasms were enrolled. A double dose of proton pump inhibitors was administered after ESD. SLE was planned 5 days after ESD. Post-ESD bleeding occurring before SLE was defined as early phase post-ESD bleeding, whereas bleeding after SLE was defined as later phase post-ESD bleeding. Forrest IIa and IIb ulcers are defined as high-risk ulcers requiring prophylactic hemostasis. We investigated risk factors for post-ESD bleeding, particularly focusing on the use of antithrombotic agents and the presence of high-risk ulcers requiring prophylactic hemostasis during SLE. RESULTS: Under a double dose of proton pump inhibitors, early phase post-ESD bleeding occurred in 2.3% of non-users (5/218) and 6.2% of users of antithrombotic agents (5/81). High-risk ulcers were found in 19.0% of the cases during scheduled SLE (55/289). Later phase bleeding occurred in 5.5% of cases [2.8% of non-users (6/213) and 13.2% of users of antithrombotic agents (10/76)]. Cox regression analysis revealed that the risk factor for post-ESD bleeding was antithrombotic treatment (HR: 3.56; 95% CI: 1.63-8.02, p = 0.002) alone. Among patients with high-risk ulcers, a statistically significant increase in bleeding was observed in the later phase in patients under antithrombotic therapy, compared to those not receiving any antithrombotic agents (p = 0.001). CONCLUSIONS: Antithrombotic treatment is a risk factor for post-ESD bleeding despite SLE being scheduled 5 days after ESD. Later phase post-ESD bleeding was observed in 13.2% of the patients under antithrombotic treatment even after prophylactic hemostasis for high-risk ulcers. TRIAL REGISTRATION: This study was registered in the UMIN Clinical Trials Registry System ( 000023306 ). Retrospectively registered on 23rd July 2016.

Oxidative stress controlling agents are effective for small intestinal injuries induced by non-steroidal anti-inflammatory drugs.

BACKGROUND AND AIM: Video-capsule endoscopy (VCE) has shown that intestinal ulcers are common in non-steroidal anti-inflammatory drugs (NSAIDs) users, although the mechanisms and management have not been clearly defined. To explore the contribution of oxidative stress and potential of anti-oxidants for NSAIDs-induced intestinal ulcers, we assessed human serum oxidative stress balance and the effect of anti-oxidants using a mouse model. METHODS: A total of 30 NSAIDs users (17 aspirin and 13 non-aspirin users) received VCE. Serum reactive oxygen metabolite (d-ROM) and antioxidative OXY-adsorbent test (OXY) were measured. The indomethacin (IND)-induced mouse intestinal ulcer model was used to assess the effect of anti-oxidants. Eight-week-old mice were divided into four groups; control diet and diet including IND (N group), IND and L-carnitine (NC group), and IND and vitamin E (NE group). RESULTS: Serum OXY levels among non-aspirin users were lower in the mucosal injuries positive group than the negative group (P < 0.05). In the mouse models, the degree of mucosal injuries was lower in NC and NE than N (P < 0.01). Serum d-ROM levels were lower in NC and NE than N (P < 0.01), and OXY levels were higher in NC than N and NE (P < 0.01). The degeneration of intestinal mitochondria was mild in NC and NE. The serum KC/CXCL-1 level and hepatic expression of the anti-oxidant molecule Gpx4 were lower in NC than N. CONCLUSIONS: Non-aspirin NSAID-induced intestinal ulcers are related to decreased anti-oxidative stress function. Anti-oxidants, especially L-carnitine, are good candidates for intestinal ulcers.

Sprouty-Related Ena/Vasodilator-Stimulated Phosphoprotein Homology 1-Domain-Containing Protein-2 Critically Regulates Influenza A Virus-Induced Pneumonia.

OBJECTIVES: Influenza A virus causes acute respiratory infections that induce annual epidemics and occasional pandemics. Although a number of studies indicated that the virus-induced intracellular signaling events are important in combating influenza virus infection, the mechanism how specific molecule plays a critical role among various intracellular signaling events remains unknown. Raf/MEK/extracellular signal-regulated kinase cascade is one of the key signaling pathways during influenza virus infection, and the Sprouty-related Ena/vasodilator-stimulated phosphoprotein homology 1-domain-containing protein has recently been identified as a negative regulator of Raf-dependent extracellular signal-regulated kinase activation. Here, we examined the role of Raf/MEK/extracellular signal-regulated kinase cascade through sprouty-related Ena/vasodilator-stimulated phosphoprotein homology 1-domain-containing protein in influenza A viral infection because the expression of sprouty-related Ena/vasodilator-stimulated phosphoprotein homology 1-domain-containing protein was significantly enhanced in human influenza viral-induced pneumonia autopsy samples. DESIGN: Prospective animal trial. SETTING: Research laboratory. SUBJECTS: Wild-type and sprouty-related Ena/vasodilator-stimulated phosphoprotein homology 1-domain-containing protein-2 knockout mice inoculated with influenza A. INTERVENTIONS: Wild-type or sprouty-related Ena/vasodilator-stimulated phosphoprotein homology 1-domain-containing protein-2 knockout mice were infected by intranasal inoculation of influenza A (A/PR/8). An equal volume of phosphate-buffered saline was inoculated intranasally into mock-infected mice. MEASUREMENTS AND MAIN RESULTS: Influenza A infection of sprouty-related Ena/vasodilator-stimulated phosphoprotein homology 1-domain-containing protein-2 knockout mice led to higher mortality with greater viral load, excessive inflammation, and enhanced cytokine production than wild-type mice. Administration of MEK inhibitor, U0126, improved mortality and reduced both viral load and cytokine levels. Furthermore, bone marrow chimeras indicated that influenza A-induced lung pathology was most severe when sprouty-related Ena/vasodilator-stimulated phosphoprotein homology 1-domain-containing protein-2 expression was lacking in nonimmune cell populations. Furthermore, microarray analysis revealed knockdown of sprouty-related Ena/vasodilator-stimulated phosphoprotein homology 1-domain-containing protein-2 led to enhanced phosphatidylinositol 3-kinase signaling pathway, resulting that viral clearance was regulated by sprouty-related Ena/vasodilator-stimulated phosphoprotein homology 1-domain-containing protein-2 expression through the phosphatidylinositol 3-kinase signaling pathway in murine lung epithelial cells. CONCLUSIONS: These data support an important function of sprouty-related Ena/vasodilator-stimulated phosphoprotein homology 1-domain-containing protein-2 in controlling influenza virus-induced pneumonia and viral replication. Sprouty-related Ena/vasodilator-stimulated phosphoprotein homology 1-domain-containing protein-2 may be a novel therapeutic target for controlling the immune response against influenza influenza A virus infection.

The earliest trough concentration predicts the dose of tacrolimus required for remission induction therapy in ulcerative colitis patients.

BACKGROUND: Oral tacrolimus therapy is effective for refractory ulcerative colitis (UC), but dose adjustment according to the trough concentrations which varies largely among individuals, is required. This study aimed to identify factors to predict the tacrolimus dose required for achieving the target trough level for remission induction of UC. METHODS: Forty-seven consecutive UC patients who were treated with tacrolimus were retrospectively analyzed. Tacrolimus doses were adjusted every 2 or 3 days to achieve trough concentrations of 10-15 ng/mL. The dose required for reaching the target trough level was analyzed based on disease characteristics, course of trough concentrations, and gene polymorphism related to tacrolimus metabolism. RESULTS: Median daily dose of tacrolimus required for achieving the target trough level was 0.19 (0.07-0.42) mg/kg, and patients were divided into high or low dose group (< 0.2 mg/kg or > 0.2 mg/kg). The value of initial trough concentration/starting dose was higher in the low dose group than in the high dose group (1.35 ng/mL/mg vs. 0.78 ng/mL/mg, p < 0.0001). Although presence of CYP3A5 *1 was more frequently observed in the high dose group, initial trough concentration was the only significant factor for determining requirement of high dose of tacrolimus (OR = 28.0, 95% confidence interval 3.20 - 631). CONCLUSIONS: The most practical predictor of the dose required for achieving the target trough concentration was the trough concentration measured 2 or 3 days after starting tacrolimus therapy. Our findings would make tarcolimus administration for UC safer, easier and more effective.

Real-world NUDT15 genotyping and thiopurine treatment optimization in inflammatory bowel disease: a multicenter study.

BACKGROUND: This study evaluated the effectiveness of NUDT15 codon 139 genotyping in optimizing thiopurine treatment for inflammatory bowel disease (IBD) in Japan, using real-world data, and aimed to establish genotype-based treatment strategies. METHODS: A retrospective analysis of 4628 IBD patients who underwent NUDT15 codon 139 genotyping was conducted. This study assessed the purpose of the genotyping test and subsequent prescriptions following the obtained results. Outcomes were compared between the Genotyping group (thiopurine with genotyping test) and Non-genotyping group (thiopurine without genotyping test). Risk factors for adverse events (AEs) were analyzed by genotype and prior genotyping status. RESULTS: Genotyping test for medical purposes showed no significant difference in thiopurine induction rates between Arg/Arg and Arg/Cys genotypes, but nine Arg/Cys patients opted out of thiopurine treatment. In the Genotyping group, Arg/Arg patients received higher initial doses than the Non-genotyping group, while Arg/Cys patients received lower ones (median 25 mg/day). Fewer AEs occurred in the Genotyping group because of their lower incidence in Arg/Cys cases. Starting with < 25 mg/day of AZA reduced AEs in Arg/Cys patients, while Arg/Arg patients had better retention rates when maintaining ≥ 75 mg AZA. Nausea and liver injury correlated with thiopurine formulation but not dosage. pH-dependent mesalamine reduced leukopenia risk in mesalamine users. CONCLUSIONS: NUDT15 codon 139 genotyping effectively reduces thiopurine-induced AEs and improves treatment retention rates in IBD patients after genotype-based dose adjustments. This study provides data-driven treatment strategies based on genotype and identifies risk factors for specific AEs, contributing to a refined thiopurine treatment approach.

Predictive Factors for Efficacy of Oral Tacrolimus Induction Therapy in Moderate to Severe Ulcerative Colitis Patients: Large Multicenter Retrospective Cohort Study.

BACKGROUND: Tacrolimus (TAC), a calcineurin inhibitor, is used for remission induction therapy in patients with moderate to severe ulcerative colitis (UC), with short-term efficacy and related predictive factors shown in previous cohort studies. However, most studies reported data for only a limited number of patients enrolled from a single center. We performed a large multicenter retrospective cohort study to identify factors related to prediction of clinical remission in UC patients treated with oral TAC. METHODS: The medical records of patients with moderate to severe UC treated with oral TAC as induction therapy at 7 institutions between April 2009 and March 2017 were retrospectively reviewed. RESULTS: A total of 216 patients who received TAC for induction were analyzed, of whom 123 (56.9%) showed clinical remission at week 12. Logistic regression analysis indicated that previous or current use of antitumor necrosis factor (TNF)-α antibodies (odds ratio [OR], 0.259; P = .006), and concomitant treatment with 5-aminosalicylate (5-ASA) at the baseline (OR, 0.268; P = .005) were independent predictive factors correlated with failure of clinical remission, whereas higher levels of C-reactive protein (OR, 1.124; P = .014) predicted achievement of clinical remission. CONCLUSIONS: Results of this multicenter study clearly indicate the efficacy of TAC induction therapy for patients with moderate to severe UC. Notably, previous or current use of anti-TNF-α antibodies was associated with poor achievement of clinical remission by week 12.

Anxiety and behavioral changes in Japanese patients with inflammatory bowel disease due to COVID-19 pandemic: a national survey.

BACKGROUND: Given the increasing health concerns for patients with inflammatory bowel disease (IBD), amidst the COVID-19 pandemic, we investigated the impact of the pandemic on the anxiety and behavioral changes in Japanese patients with IBD. METHODS: We analyzed 3032 questionnaires from patients with IBD, aged 16 years or older visiting 30 hospitals and 1 clinic between March 2020 and June 2021. The primary outcome was the score of the anxiety experienced by patients with IBD during the pandemic. RESULTS: Participants reported a median age of 44 years; 43.3% of the patients were women. Moreover, 60.6% and 39.4% were diagnosed with ulcerative colitis and Crohn's disease, respectively, with a median disease duration of 10 years. Participants indicated an average of disease-related anxiety score of 5.1 ± 2.5 on a ten-point scale, with a tendency to increase, 1 month after the number of infected persons per population increased. The top three causes for anxiety were the risk of contracting COVID-19 during hospital visits, SARS-CoV-2 infection due to IBD, and infection by IBD medication. Factors associated with anxiety were gender (women), being a homemaker, hospital visit timings, mode of transportation (train), use of immunosuppressive drugs, and nutritional therapy. Most patients continued attending their scheduled hospital visits, taking their medications, experienced the need for a family doctor, and sought guidance and information regarding COVID-19 from primary doctors, television, and Internet news. CONCLUSIONS: Patients with IBD experienced moderate disease-related anxiety due to the pandemic and should be proactively informed about infectious diseases to relieve their anxiety.

Safety and efficacy of capsule endoscopy for patients with newly diagnosed Crohn's disease: A multicenter retrospective study.

Crohn's disease (CD) is a chronic inflammatory disease that develops at a young age and frequently leads to intestinal resection. Capsule endoscopy (CE) can directly and non-invasively inspect the entire small bowel mucosa. We suspected that CE could be a good diagnostic tool for detecting CD in young patients. The aim of this study was to investigate the safety and efficacy of CE in patients with newly diagnosed CD and to evaluate the CE findings, especially in the upper small bowel of young patients. We retrospectively investigated 32 patients with newly diagnosed CD from 5 institutions. Patient characteristics, clinical course, and characteristics of CE findings were analyzed. The total small intestine observation rate was 93%, and the retention rate was 3% (1/32). No abnormality was identified by ileocolonoscopy in 46% (15/32), and transition of small bowel lesions (TSL) was found in 35% (12/34) of the patients. The frequency of longitudinal ulcers and cobblestones in the upper small intestine was significantly higher in younger patients (≤20 years). Moreover, positive findings in the upper small intestine were predominantly observed in younger patients (≤20 years). CE for patients with newly diagnosed CD was safe and useful, especially for the detection of upper small bowel lesions in young patients.

Clinicopathological Characteristics of Superficial Barrett's Adenocarcinoma in a Japanese Population: A Retrospective, Multicenter Study.

Objective Although Barrett's adenocarcinoma (BA) remains a minor disease in Japan, its incidence has been gradually increasing. We analyzed the characteristics of BA in Japanese populations. Methods We retrospectively reviewed medical records and analyzed the clinicopathological differences between short-segment Barrett's esophagus (SSBE) and long-segment Barrett's esophagus (LSBE), as well as metastasis. Local recurrence and metachronous lesions were analyzed only in patients who underwent endoscopic resection (ER). Patients Consecutive patients who had pathological T1 BAs resected by ER or surgery from January 2003 to December 2017. Results A total of 168 patients were analyzed, including 139 with SSBE and 29 with LSBE. In total, 67% of the SSBE lesions and 32% of the LSBE lesions were located between 0 and 3 o'clock (p=0.0014). No patients who achieved pathological margin-free resection (pR0) and 17% of patients who did not achieve pR0 experienced local recurrence (p=0.0131). None of the patients without lymphovascular involvement, a poorly differentiated component, lesion size of >30 mm, and submucosal invasion of >500 µm experienced metastasis. The 5-year cumulative incidence rate of metachronous BA after ER was 0% in patients with SSBE and 40% in patients with LSBE (p=0.0005). Conclusion Superficial BA was likely to be detected at the right anterior wall of SSBE in the Japanese population. The risk for metachronous BA after ER was high in Japanese patients with LSBE, as in Western patients.

Comparison of Nonesophageal Eosinophilic Gastrointestinal Disorders with Eosinophilic Esophagitis: A Nationwide Survey.

BACKGROUND: Eosinophilic esophagitis (EoE) has increased rapidly and has been well characterized. However, no nationwide survey has been conducted regarding non-esophageal eosinophilic gastrointestinal disorders (non-EoE EGIDs), and they remain poorly understood. OBJECTIVE: To compare the clinical features and natural histories of non-EoE EGIDs and EoE by using the same questionnaire, for all ages. METHODS: We conducted a nationwide hospital-based survey of patients who visited hospitals from January 2013 through December 2017. We randomly selected 10,000 hospitals that perform endoscopy. We analyzed the demographics, symptoms, gastrointestinal histology, treatments, and natural histories of EoE and non-EoE EGIDs. RESULTS: A total of 2906 hospitals responded to the questionnaire. We identified 1542 patients and obtained detailed data for 786 patients, consisting of 39% EoE and 61% non-EoE EGIDs. The clinical characteristics were analyzed for patients who met the "definite" criteria that excluded comorbidities. Non-EoE EGIDs showed no gender difference, whereas EoE was male-predominant. Tissue eosinophilia was often seen in the small intestine (62%) and stomach (49%). The frequency of hypoproteinemia was high (27%) in childhood. Children also had more serious symptoms and complications than adults: restriction of daily life activity (P = .009), failure to grow/weight loss (P = .008), and surgery (P = .01). For both diseases, the most common natural history was the continuous type: 66% (95% confidence interval [CI]: 58-74) in EoE and 64% (95% CI: 55-72) in non-EoE EGIDs. CONCLUSIONS: The percentage of persistent patients with non-EoE EGIDs was almost the same as those with EoE. Complications were more frequent in children than in adults.

Neuroendocrine carcinoma arising from Barrett's esophageal adenocarcinoma: a case report.

Neuroendocrine carcinoma in Barrett's esophagus is rare and its developmental mechanisms remain unclear. Neuroendocrine carcinoma arising in Barrett's esophagus with adenocarcinoma was detected at an early stage and resected by endoscopic submucosal dissection. Detailed pathological examination revealed that the neuroendocrine carcinoma originated via differentiation of the preexisting adenocarcinoma. A 79-year-old man presented with a flat protruding lesion in the esophagogastric junction. Esophagogastroduodenoscopy revealed a red flat 10-mm protruding lesion in the Barrett's epithelium and a shallow depression at the distal end. Narrow band imaging with magnification showed that the blood vessels in the protrusion were dilated and meandered irregularly, while those in the depression were small and did not form a network; the blood vessels were missing in some parts of the depression. Well-differentiated adenocarcinoma was diagnosed after analysis of the biopsy specimen of the protrusion, and endoscopic submucosal dissection was performed. The pathological diagnosis was neuroendocrine carcinoma with an adenocarcinoma component.

Observer agreement for the diagnosis of intestinal acute graft-vs.-host disease based on the presence of villous atrophy in the terminal ileum.

Intestinal graft-vs.-host disease (GVHD) is a serious complication of allo-hematopoietic stem cell transplantation (allo-HSCT). Villous atrophy in the terminal ileum is considered a useful diagnostic indicator for GVHD. However, the inter- and intra-observer agreement regarding the ileocolonoscopic findings indicative of acute intestinal GVHD, i.e., villous atrophy in the terminal ileum, are currently insufficient in multiple institutions. Thus, the present study aimed to investigate the incidence of villous atrophy in the terminal ileum to diagnose acute intestinal GVHD and determine the inter- and intra-observer agreement regarding this result for experienced endoscopists from multiple institutions. Consecutive patients who underwent allo-HSCT were referred to our institution between May 2008 and September 2015. A total of 54 patients underwent total ileocolonoscopy after allo-HSCT due to suspected intestinal acute GVHD. Subsequently, three observers from different institutions evaluated the cases for the presence of villous atrophy in the terminal ileum. In this study, the pathology results were a gold standard to evaluate the predictive value of ileocolonoscopy detection. Definitive pathological and non-pathological GVHD was diagnosed in 22 and 32 cases, respectively. The results of examining whether villous atrophy could predict GVHD were as follows. For three observers (A, B and C), the sensitivity of villous atrophy in the terminal ileum was 86.4, 77.3 and 79.2%, respectively, whereas the specificity was 62.5, 62.5 and 86.7%, respectively. The positive predictive value (PPV) and negative predictive value (NPV) of villous atrophy for GVHD were as follows: The PPV of appearance was 61.3, 58.6 and 82.6%, respectively, whereas the NPV was 87.0, 80.0 and 83.9%, respectively. Kappa coefficients for the inter-observer reliability were 0.85, 0.63 and 0.63 for observers A and B, A and C, and B and C, respectively. The intra-observer kappa coefficient was 0.88 for observer A, 0.73 for observer B and 0.75 for observer C. A substantial observer agreement was achieved for the analysis of villous atrophy in the terminal ileum and the agreement for the predictive histological diagnosis was also excellent. Based on the results of the present study, identification of villous atrophy in the terminal ileum was a clinically effective diagnostic parameter, even if different endoscopists were involved in the diagnosis at multiple institutions. The present study was registered as a trial with the University Hospital Medical Information Network (UMIN; registration no. UMIN000025390).