Precancerous nature of intestinal metaplasia with increased chance of conversion and accelerated DNA methylation.

OBJECTIVE: The presence of intestinal metaplasia (IM) is a risk factor for gastric cancer. However, it is still controversial whether IM itself is precancerous or paracancerous. Here, we aimed to explore the precancerous nature of IM by analysing epigenetic alterations. DESIGN: Genome-wide DNA methylation analysis was conducted by EPIC BeadArray using IM crypts isolated by Alcian blue staining. Chromatin immunoprecipitation sequencing for H3K27ac and single-cell assay for transposase-accessible chromatin by sequencing were conducted using IM mucosa. NOS2 was induced using Tet-on gene expression system in normal cells. RESULTS: IM crypts had a methylation profile unique from non-IM crypts, showing extensive DNA hypermethylation in promoter CpG islands, including those of tumour-suppressor genes. Also, the IM-specific methylation profile, namely epigenetic footprint, was present in a fraction of gastric cancers with a higher frequency than expected, and suggested to be associated with good overall survival. IM organoids had remarkably high NOS2 expression, and NOS2 induction in normal cells led to accelerated induction of aberrant DNA methylation, namely epigenetic instability, by increasing DNA methyltransferase activity. IM mucosa showed dynamic enhancer reprogramming, including the regions involved in higher NOS2 expression. NOS2 had open chromatin in IM cells but not in gastric cells, and IM cells had frequent closed chromatin of tumour-suppressor genes, indicating their methylation-silencing. NOS2 expression in IM-derived organoids was upregulated by interleukin-17A, a cytokine secreted by extracellular bacterial infection. CONCLUSIONS: IM cells were considered to have a precancerous nature potentially with an increased chance of converting into cancer cells, and an accelerated DNA methylation induction due to abnormal NOS2 expression.

Fundic gland polyps related to diverse aetiologies show subtle morphological differences: a multicentre retrospective study.

AIMS: Fundic gland polyps (FGPs) comprise 66% of all gastric polyps. Although they are usually non-syndromic, they may be associated with various syndromes, including familial adenomatous polyposis (FAP) or gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS). We aimed to evaluate how histological features relate to distinct FGP subtypes. METHODS AND RESULTS: We performed a retrospective analysis of 118 FGPs from 109 patients for the architecture of fundic glands, microcyst lining, parietal cell hyperplasia and surface foveolar epithelial changes. Age, gender and history of FAP or GAPPS were collected. Based on combinations of histological features, three distinct patterns (A, B and C) of FGPs were delineated and correlated to the aetiologies. Non-syndromic FGPs were well-formed polyps composed of disordered fundic glands with intermediate-sized microcysts typically lined by a mixture of oxyntic and mucin-secreting cells (73%). Parietal cell hyperplasia (80%) and foveolar surface hyperplasia (78%) were common. FAP-associated cases demonstrated small microcysts that were predominantly lined by fundic epithelium (77%), with limited parietal cell hyperplasia (27%); foveolar hyperplasia was uncommon. GAPPS-related polyps were the largest, with prominent, mucin-secreting epithelium-lined microcysts (73%). Hyperproliferative aberrant pits were universally present, whereas parietal cell hyperplasia was uncommon. Pattern A was identified in most non-syndromic FGPs (74%) and in a minority of FAP-related FGPs (26%). The majority (82%) of FAP-related FGPs showed pattern B, but only 18% of non-syndromic FGPs did. Pattern C consisted exclusively of GAPPS-associated polyps. CONCLUSIONS: We conclude that, although FGPs share similar histomorphology, subtle differences exist between polyps of different aetiology. In the appropriate clinical setting, the recognition of these variations may help to consider syndromic aetiologies.

Potential association of eEF1A dimethylation at lysine 55 in the basal area of Helicobacter pylori-eradicated gastric mucosa with the risk of gastric cancer: a retrospective observational study.

BACKGROUND: Although eradication therapy for chronic Helicobacter pylori (H. pylori) reduces the risk of gastric cancer (GC), its effectiveness is not complete. Therefore, it is also critically important to identifying those patients who remain at high risk after H. pylori eradication therapy. Accumulation of protein methylation is strongly implicated in cancer, and recent study showed that dimethylation of eEF1A lysine 55 (eEF1AK55me2) promotes carcinogenesis in vivo. We aimed to investigate the relationship between eEF1A dimethylation and H. pylori status, efficacy of eradication therapy, and GC risk in H. pylori-eradicated mucosa, and to reveal the potential downstream molecules of eEF1A dimethylation. METHODS: Records of 115 patients (11 H. pylori-negative, 29 H. pylori-positive, 75 post-eradication patients) who underwent upper gastrointestinal endoscopy were retrospectively reviewed. The eEF1A dimethyl level was evaluated in each functional cell type of gastric mucosa by immunofluorescent staining. We also investigated the relationship between eEF1AK55me2 downregulation by CRISPR/Cas9 mediated deletion of Mettl13, which is known as a dimethyltransferase of eEF1AK55me2. RESULTS: The level of eEF1A dimethylation significantly increased in the surface and basal areas of H. pylori-positive mucosa compared with the negative mucosa (surface, p = 0.0031; basal, p = 0.0036, respectively). The eEF1A dimethyl-levels in the surface area were significantly reduced by eradication therapy (p = 0.005), but those in the basal area were maintained even after eradication therapy. Multivariate analysis revealed that high dimethylation of eEF1A in the basal area of the mucosa was the independent factor related to GC incidence (odds ratio = 3.6611, 95% confidence interval = 1.0350-12.949, p = 0.0441). We also showed the relationship between eEF1A dimethylation and expressions of reprogramming factors, Oct4 and Nanog, by immunohistochemistry and in vitro genome editing experiments. CONCLUSIONS: The results indicated that H. pylori infection induced eEF1A dimethylation in gastric mucosa. The accumulation of dimethyl-eEF1A in the basal area of the mucosa might contribute to GC risk via regulation of reprograming factors in H. pylori eradicated-gastric mucosa.

Prediction of tissue origin of adenocarcinomas in the esophagogastric junction by DNA methylation.

BACKGROUND: Prediction of tissue origin of esophagogastric junction (EGJ) adenocarcinomas can be important for therapeutic decision, but no molecular marker is available. Here, we aimed to develop such a marker taking advantage of tissue-specific profiles of DNA methylation. METHODS: DNA methylation profiles of gastric adenocarcinomas (GACs) were obtained by an Infinium HumanMethylation450 BeadChip array, and those of esophageal adenocarcinoma (EACs) were obtained from the TCGA database. DNA from formalin-fixed paraffin-embedded (FFPE) samples was analyzed by bisulfite pyrosequencing. RESULTS: In the screening set, 51 of 145,841 CpG sites in CpG islands were methylated at significantly higher levels in 30 GACs compared to those in 30 EACs. Among them, SLC46A3 and cg09177106 were unmethylated in all the 30 EACs. Predictive powers of these two markers were successfully confirmed in an independent validation set (18 GACs and 18 EACs) (SLC46A3, sensitivity = 77.8%, specificity = 100%; cg09177106, sensitivity = 83.3%, specificity = 94.4%), and could be applied to FFPE samples (37 GACs and 18 EACs) (SLC46A3, P = 0.0001; cg09177106, P = 0.0028). On the other hand, EAC-specific markers informative in the FFPE samples could not be isolated. Using these GAC-specific markers, nine of 46 (19.6%) TCGA EGJ adenocarcinomas were predicted to be GACs. CONCLUSIONS: Two GAC-specific markers, SLC46A3 and cg09177106, had a high specificity for identifying the tissue origin of EGJ adenocarcinoma.

Analysis of long-term serological and histological changes after eradication of Helicobacter pylori.

Stratification of gastric cancer risk by measuring serological biomarkers is useful for screening of gastric cancer. However, this method has problem such as overlooking past infected patients. We aimed to evaluate the association between Helicobacter pylori infection status and serological biomarkers. We divided 5,268 patients according to Helicobacter pylori infection status and past infected patients were divided into 12 groups according to time elapsed since eradication. We analyzed mean serum H. pylori immunoglobulin G antibody, pepsinogen titers, histological and endoscopic atrophy score of each group. Mean H. pylori immunoglobulin G antibody showed a decreasing tendency, there was no significant difference from the uninfected group at 11 years after eradication (p = 0.19). PGI, PGII decreased in short term after eradication. However, both PGI and PGII gradually increased as long-term changes after eradication, became comparable to those in the uninfected group (p = 0.41, p = 0.37, respectively). Histological atrophy improved gradually, became equivalent to uninfected group. Endoscopic atrophy score did not improve for long term after eradication. In conclusion, patients with long term after eradication reach the uninfected condition serologically, histologically. Endoscopic assessment of gastric mucosal atrophy may be useful for accurate assessment of gastric cancer risk.

Gastric mucosal changes, and sex differences therein, after Helicobacter pylori eradication: A long-term prospective follow-up study.

BACKGROUND AND AIM: Improvement of atrophic gastritis and intestinal metaplasia (IM) is considered to reduce the gastric cancer risk, but whether it can be achieved by H. pylori eradication (HPE) remains controversial. To evaluate the effect of HPE, we observed the gastric mucosa for up to17 years after HPE and sex differences in gastric mucosa. METHODS: In total, 172 patients (94 males, 78 females) with HPE were enrolled. Annual histological evaluations were performed for up to 17 years. The grades of mononuclear cells, neutrophils, atrophy, IM in the antrum and corpus were evaluated using the updated Sydney system. RESULTS: Relative to the pre-HPE period, atrophy had improved significantly 1 year after HPE in the antrum (1.50 ± 0.75 vs. 1.21 ± 1.25, P < 0.01) and corpus (0.59 ± 0.75 vs. 0.18 ± 0.52, P < 0.05). IM showed no significant change during 17 years after HPE at either biopsy site. Atrophy scores did not differ significantly between males and females. IM scores were significantly higher in males than in females before eradication (antrum, 0.67 ± 0.94 vs. 0.44 ± 0.77, P = 0.003, corpus, 0.20 ± 0.62 vs. 0.047 ± 0.21, P = 0.0027) and at most observation timepoints. CONCLUSIONS: During 17 years after HPE, atrophy, but not IM, improved significantly at the greater curvatures of the antrum and corpus. IM was significantly more severe in males than in females. Careful follow-up after HPE based on sex differences in gastric mucosal characteristics is important.

Development of Pancreatic Acinar Cell Metaplasia During Gastric Repair in a Rat Duodenal Contents Reflux Model.

BACKGROUND: We previously reported the development of pancreatic acinar cell metaplasia (PACM) in the glandular stomach of a duodenal contents reflux model (reflux model). AIMS: We aimed to investigate the characteristics and histogenesis of PACM using a reflux model. METHODS: A reflux model was created using 8-week-old male Wistar rats, which were killed up to 30 weeks postoperatively. Histological examination was performed to analyze the glandular stomach-jejunal anastomosis. Furthermore, electron microscopic images of PACM samples were compared with pancreatic and gastric glands removed from rats that had not undergone surgery. Immunostaining for α-amylase, HIK1083, TFF2, and Ki-67 was performed, and double fluorescent staining was carried out using antibodies against α-amylase and HIK1083, or α-amylase and TFF2. RESULTS: In all reflux model rats, PACM was observed proximal to the glandular stomach-jejunal anastomosis, surrounded by pseudopyloric metaplasia. The number of chief cells was decreased in the deep part of the gland, where PACM occurred. Electron microscopy showed that PACM cells had greater numbers of rough endoplasmic reticulum tubules than chief cells, and exhibited pancreatic acinar cell morphology. Upon immunochemical staining, the regenerative foveolar epithelium and part of the pseudopyloric glands stained strongly positive for TFF2, whereas PACM cells were only weakly positive. Double fluorescent staining identified early lesions of PACM in the neck, which were double positive for α-amylase and TFF2, but negative for HIK1083. CONCLUSIONS: PACM could be induced by duodenal contents reflux. PACM originates from stem cells located in the neck of oxyntic glands during gastric mucosal regeneration.

Immunohistochemical differences in gastric mucosal damage between nodular and non-nodular gastritis caused by Helicobacter pylori infection.

In this study, the level of cell damage were analyzed immuno-histochemically to clarify the association between nodular gastritis and undifferentiated gastric cancer. Thirty patients of nodular gastritis were enrolled as the nodular gastritis group. Thirty patients of non-nodular gastritis were enrolled as the control group. They were evaluated according to the updated Sydney system and used for immunohistochemical staining (p53, Ki-67, E-cadherin, and 8-OHdG). The scores based on the updated Sydney system were significantly higher in the nodular group than in the non-nodular group for histologically assessed inflammation and activity in the gastric corpus (1.91 ±â€„0.77 vs 1.58 ±â€„0.60, p = 0.049, 0.83 ±â€„0.81 vs 0.44 ±â€„0.64, p = 0.032). On immunostaining, the detection of E-cadherin was lower in the nodular group for both the antrum (1.0 ±â€„0.62 vs 1.47 ±â€„0.85, p = 0.047) and the corpus (1.16 ±â€„0.81 vs 1.48 ±â€„0.71, p = 0.043) and the p53 labeling index of the gastric corpus was higher in the nodular group than in the non-nodular group (3.06 ±â€„1.94 vs 2.03 ±â€„1.99, p = 0.015). Nodular gastritis showed significant severe inflammation and immunohistochemical cell damage compared with non-nodular gastritis. These findings may play an important role in the oncogenesis of undifferentiated gastric cancer in nodular gastritis.

Influence of acotiamide on 13C-urea breath test for Helicobacter pylori diagnosis.

The Helicobacter pylori infection and functional dyspepsia are often coexisted. The effect of acotiamide, a drug for functional dyspepsia, on the result of Helicobacter pylori diagnosis has yet to be studied. We evaluated the influence of acotiamide on the results of Helicobacter pylori diagnosis in the 13C-urea breath test. Twenty patients with Helicobacter pylori-positive functional dyspepsia were treated with 100 mg of acotiamide three times a day for two weeks. Changes in 13C-urea breath test were investigated before and after administration, and two weeks after administration as the follow-up period. The 13C-urea breath test and the medical questionnaire of modified frequency scale for the symptoms of gastroesophageal reflux disease were conducted at every period. Nineteen patients were included for analysis. No patients showed negative in 13C-urea breath test at Weeks 2 and 4. On the symptom scale, dyspepsia and total scores decreased from Week 0 to Week 2 and increased from Week 2 to Week 4, and the improvement rates of the dyspepsia score at Week 2 was 63%. In conclusion, we confirmed that acotiamide is unlikely to influence the result of 13C-urea breath test and it may improve the symptoms of functional dyspepsia during Helicobacter pylori eradication treatment.

Histological analysis of fundic gland polyps secondary to PPI therapy.

AIMS: The aim of this study was to clarify the histopathological features of fundic gland polyps (FGPs) in patients treated with proton pump inhibitors (PPIs) and to investigate the mechanism of enlargement of FGPs after PPI treatment. METHODS AND RESULTS: A total of 196 biopsy specimens of FGPs, which consisted of 87 FGPs in patients treated with PPIs (PPI group) and 109 FGPs in patients treated without PPIs (non-PPI group) were compared histologically using haematoxylin and eosin staining, Ki67 immunohistochemistry and multiplex immunohistochemical stain with Ki67, MUC5AC and MUC6. The significant histological features of FGPs in the PPI group were: larger size of dilated fundic gland cysts, larger number of foveolar and mixture type fundic gland cysts, foveolar cell hyperplasia, parietal cell protrusion, mononuclear cell infiltration and a higher percentage of Ki67-positive cells in the deeper layers of the glands. Multiplex immunohistochemical stain showed that Ki67-positive cells were also positive for MUC5AC, and the Ki67-positive rate was significantly higher in MUC5AC-positive cells of the PPI group than of the non-PPI group. Gene mutations of ß-catenin were found in only 9.7% of FGPs in the PPI group. CONCLUSIONS: Enlargement of fundic gland cysts due to foveolar cell proliferation and parietal cell protrusion might promote the enlargement of FGPs in patients treated with PPIs. ß-catenin gene mutations might not be associated with these histological changes of FGPs after PPI treatment.

No transformation of a fundic gland polyp with dysplasia into invasive carcinoma after 14 years of follow-up in a proton pump inhibitor-treated patient: A case report.

A fundic gland polyp (FGP) is a common gastric polyp. Intraepithelial neoplasia in FGPs, referred to as FGP with dysplasia, is often seen in patients with familial adenomatous polyposis (FAP). In sporadic FGPs, low-grade dysplasia (LGD) is rare, and high-grade dysplasia (HGD) or carcinoma arising from sporadic FGPs is extremely rare. Because of this rarity, the prognosis and appropriate management of these lesions have not been clarified. In the present case, a sporadic FGP with LGD did not develop into invasive carcinoma, but contained foci of HGD 14 years after diagnosis. The biopsy specimen of the polyp taken at the first esophagogastroduodenoscopy 15 years earlier was diagnosed as FGP without dysplasia. At the second histological examination, LGD was found. Because the polyp increased in size during proton pump inhibitor therapy for 14 years, endoscopic mucosal resection was performed. The pathological diagnosis of the resected specimen was FGP with HGD mixed in LGD, with no invasive carcinoma. Dysplasia in FGPs might have less malignant potential regardless of dysplasia or size.

A case of an intractable duodenal ulcer associated with a pancreatic arteriovenous malformation.

A 62-year-old man with epigastralgia was referred to our hospital for the evaluation of an intractable duodenal ulcer, which did not improve following proton pump inhibitor treatment. An upper gastrointestinal endoscopy revealed that the base of the ulcer was gray-white in color with conspicuous fibrosis tissue, unlike the appearance of common ulcers. A contrast-enhanced abdominal CT scan and angiography revealed tortuous and dilated vascular structures in the pancreatic head. This was diagnosed as a pancreatic arteriovenous malformation. We suggest that the intractable duodenal ulcer was caused by the pancreatic arteriovenous malformation. Therefore, we performed a pancreaticoduodenectomy. Pancreatic arteriovenous malformations should be considered as one of the causes of treatment-resistant duodenal ulcers.

Ocular Behçet's disease is less complicated with allergic disorders. A nationwide survey in Japan.

OBJECTIVES: Behçet's disease (BD) is a systemic inflammatory disorder polarised to the Th1 and Th17 immune systems. Allergic diseases are polarised to the Th2 immune system. The aim of the present study is to investigate the prevalence of allergic diseases in patients who have BD. METHODS: The study involved a large-scale interview survey of Japanese patients with BD at 21 institutes of ophthalmology; 353 patients (255 males and 98 females) were recruited for this study. We analysed the history of allergic diseases such as atopic dermatitis (AD), allergic rhinitis (AR), bronchial asthma (BA) and drug/food allergies (FA). RESULTS: Oral aphthous ulcers, ocular lesions, skin lesions, genital ulcers, arthritis, neurological lesions, intestinal lesions, deep vein thrombosis and epididymitis were reported in 95.8%, 98.6%, 72.5%, 44.8%, 13.9%, 6.8%, 6.2%, 3.7% and 1.4% of the patients, respectively. It was also reported that 73 patients (20.7%) had histories of allergic diseases: AD (5 cases, 1.4%), AR (36 cases, 10.2%), BA (19 cases, 5.4%) and FA (30 cases, 8.5%). This percentage was significantly lower than in a survey that Japan's Ministry of Health, Labour and Welfare conducted for healthy population (47.6%) (odds ratio = 0.29, 95% confidence interval = 0.22-0.38, p=4.9×10-22). Frequencies of posterior/pan-uveitis, relatively severe ocular findings, and visual prognosis were not affected by a history of allergic diseases in BD. CONCLUSIONS: Patients with BD had fewer complications from allergic diseases than did the entire population of Japan.

Tapeworm Infection Diagnosed after Campylobacter jejuni-induced Enteritis.

A 35-year-old man with fever and diarrhea visited our hospital because of white string-like fecal excretion. Based on a morphological examination of the excreted object, a Diphyllobothrium infection was suspected. Additionally, Gram staining of a fecal sample revealed Campylobacter infection. After the intraduodenal administration of meglumine/diatrizoate sodium, the tapeworm was excreted. A polymerase chain reaction-based DNA sequence analysis demonstrated that the tapeworm excreted in this case was Diphyllobothrium nihonkaiensis. This report presents a rare case of coinfection with Diphyllobothrium nihonkaiensis and Campylobacter jejuni. Therefore, it is important to consider the coexistence of other intestinal infections when diagnosing parasitic infections in patients with fever.

Severe induction of aberrant DNA methylation by nodular gastritis in adults.

BACKGROUND: Nodular gastritis (NG) is characterized by marked antral lymphoid follicle formation, and is a strong risk factor for diffuse-type gastric cancer in adults. However, it is unknown whether aberrant DNA methylation, which is induced by atrophic gastritis (AG) and is a risk for gastric cancer, is induced by NG. Here, we analyzed methylation induction by NG. METHODS: Gastric mucosal samples were obtained from non-cancerous antral tissues of 16 NG and 20 AG patients with gastric cancer and 5 NG and 6 AG patients without, all age- and gender-matched. Genome-wide methylation analysis and expression analysis were conducted by a BeadChip array and RNA-sequencing, respectively. RESULTS: Clustering analysis of non-cancerous antral tissues of NG and AG patients with gastric cancer was conducted using methylation levels of 585 promoter CpG islands (CGIs) of methylation-resistant genes, and a large fraction of NG samples formed a cluster with strong methylation induction. Promoter CGIs of CDH1 and DAPK1 tumor-suppressor genes were more methylated in NG than in AG. Notably, methylation levels of these genes were also higher in the antrum of NG patients without cancer. Genes related to lymphoid follicle formation, such as CXCL13/CXCR5 and CXCL12/CXCR4, had higher expression in NG, and genes involved in DNA demethylation TET2 and IDH1, had only half the expression in NG. CONCLUSIONS: Severe aberrant methylation, involving multiple tumor-suppressor genes, was induced in the gastric antrum and body of patients with NG, in accordance with their high gastric cancer risk.

Characterization of residual cancer by comparison of a pair of organoids established from a patient with esophageal squamous cell carcinoma before and after neoadjuvant chemotherapy.

Neoadjuvant chemotherapy (NAC) followed by surgery is a standard approach for management of locally advanced esophageal squamous cell carcinoma (ESCC). Patients who do not respond well to NAC have a poor prognosis. Despite extensive research, the mechanisms of chemoresistance in ESCC remain largely unknown. Here, we established paired tumor organoids-designated as PreNAC-O and PostNAC-O-from one ESCC patient before and after NAC, respectively. Although the two organoids did not exhibit significant differences in proliferation, morphology or drug sensitivity in vitro, the tumorigenicity of PostNAC-O in vivo was significantly higher than that of PreNAC-O. Xenografts from PreNAC-O tended to exhibit keratinization, while those from PostNAC-O displayed conspicuous necrotic areas. The tumorigenicity of PostNAC-O xenografts during the chemotherapy was comparable to that of PreNAC-O without treatment. Furthermore, the gene expression profiles of the xenografts suggested that expression of genes involved in the EMT and/or hypoxia response might be related to the tumorigenicity of PostNAC-O. Our data suggested that the tumorigenicity of residual cancer had been enhanced, outweighing the effects of chemotherapy, rather than being attributable to intrinsic chemoresistance. Further studies are required to clarify the extent to which residual cancers share a common mechanism similar to that revealed here.

Comparison of the improvement in gastric mucosal tissue after Helicobacter pylori eradication between young and elderly people.

BACKGROUND AND STUDY AIMS: Helicobacter pylori (H. pylori) infection has been clearly shown to be a cause of gastric cancer, and the incidence of gastric cancer has been shown to decrease with eradication. However, few reports have described the utility of eradication therapy in elderly people. Thus, an investigation focusing on how much actual histological improvement is obtained with eradication therapy in elderly people was conducted. PATIENTS AND METHODS: This was a retrospective study conducted using medical information of patients diagnosed with H. pylori-associated gastritis and who underwent eradication therapy. The histological improvement was assessed based on changes in the atrophy and intestinal metaplasia scores of the Updated Sydney system from before to after eradication. We investigated the rates of histological improvement in atrophy and intestinal metaplasia one year after and long term more than five years after H. pylori eradication in an elderly group and a younger group. RESULTS: This study included 221 patients (elderly group 123, younger group 98). In histological atrophy, higher rates of improvement were seen in the corpus than in the antrum, and the rates of cure in the antrum were lower in elderly group than in younger group (p = 0.0282). With regard to intestinal metaplasia, the rates of improvement in the antrum were lower in elderly group than in younger. In long term observation, although the rates of cure in the antrum were lower in elderly, improvements were seen in atrophy scores in most of the patients and intestinal metaplasia scores in about half of patients. CONCLUSION: Though there is more obvious improvement in the gastric mucosa when H. pylori eradication therapy is performed at a young age, some mucosal improvement can be expected in about half of patients after eradication, even in elderly people.

Usefulness of AI-Equipped Endoscopy for Detecting Colorectal Adenoma during Colonoscopy Screening: Confirm That Colon Neoplasm Finely Can Be Identified by AI without Overlooking Study (Confidential Study).

In the present prospective case series study, we investigated the lesion-detection ability of an AI-equipped colonoscopy as an addition to colonoscopy (CS) screening. Participants were 100 patients aged ≥20 years who had not undergone CS at the study site in the last 3 years and passed the exclusion criteria. CS procedures were conducted using conventional white light imaging and computer-aided detection (CADe). Adenoma detection rate (ADR; number of individuals with at least one adenoma detected) was compared between the conventional group and the CADe group. Of the 170 lesions identified, the ADR of the CADe group was significantly higher than the ADR of the conventional group (69% vs. 61%, p = 0.008). For the expert endoscopists, although ADR did not differ significantly, the mean number of detected adenomas per procedure (MAP) was significantly higher in the CADe group than in the conventional group (1.7 vs. 1.45, p = 0.034). For non-expert endoscopists, ADR and MAP were significantly higher in the CADe group than in the conventional group (ADR 69.5% vs. 56.6%, p = 0.016; MAP 1.66 vs. 1.11, p < 0.001). These results indicate that the CADe function in CS screening has a positive effect on adenoma detection, especially for non-experts.

Acute Cholecystitis Associated with Eosinophilic Granulomatosis with Polyangiitis That Responded to Glucocorticoid Therapy.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic disorder characterized by tissue eosinophilic infiltration and vasculitis. Although EGPA causes multiple organ damage, it causes cholecystitis less frequently. We herein report a case of acute cholecystitis associated with EGPA in which successful treatment with glucocorticoid therapy allowed surgery to be avoided. EGPA can present as acute cholecystitis. It is important not to overlook acute cholecystitis associated with EGPA in patients with abdominal pain with peripheral eosinophilia. Furthermore, in cases of mild cholecystitis associated with EGPA that are diagnosed preoperatively, cholecystectomy might be avoided with conservative glucocorticoid treatment.

Tocilizumab-induced mucosal injury in the terminal ileum mimicking intestinal Behçet's disease: A case report.

RATIONALE: Tocilizumab, a humanized anti-interleukin-6 (IL-6) receptor monoclonal antibody, is used for the treatment of adult-onset Still disease (AOSD). Despite its efficacy in many clinical situations, concerns have been raised regarding intestinal mucosal injury in patients receiving tocilizumab. PATIENT CONCERNS: A 64-year-old woman with a history of AOSD was admitted to our hospital with hematochezia. She had AOSD for 15 years and underwent treatment with biweekly tocilizumab 9 months prior to admission. Colonoscopy revealed a large punched-out ulcer in the terminal ileum. On pathological evaluation, nonspecific enteritis with lymphocytes and eosinophils were seen. Based on the location and shape of the lesion, we suspected intestinal Behçet's disease. However, the ulcer reduced in size over time by discontinuation of tocilizumab without additional drug treatment, indicating that it was a drug-induced ulcer. DIAGNOSIS: The patient was diagnosed with tocilizumab-induced small intestinal ulcer. INTERVENTIONS: The patient treated with the discontinuation of tocilizumab. OUTCOMES: The discontinuation of tocilizumab resulted in ulcer scarring. There was no recurrence of hematochezia. LESSONS: Tocilizumab can cause deep ulcerative lesions in the terminal ileum, which may resemble intestinal Behçet's disease. It is important to continuously monitor abdominal symptoms during tocilizumab therapy and aggressively perform colonoscopy when hematochezia or abdominal pain is observed.