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.

Association Between Sense of Coherence, Disease-Specific Symptoms, and Health-Related Quality of Life Among Japanese Patients with Ulcerative Colitis: A Cross-Sectional Study.

INTRODUCTION: We examined the associations among disease-related symptoms, health-related quality of life (HRQOL), and sense of coherence (SOC) in Japanese patients with ulcerative colitis (UC). METHODS: This cross-sectional survey involved patients and physicians at 23 hospitals specializing in UC treatment in Japan (December 2019-December 2020). Multiple linear regression analysis was performed using scores on the Mental Health and General Health subscales of the Medical Outcomes Study 36-Item Short-Form Health Survey as outcomes and SOC as the main independent variable. Scores on the Inflammatory Bowel Disease Questionnaire (IBDQ) and Fecal Incontinence Quality of Life Scale (FIQL) were used to measure the effect of disease-related symptoms. The moderating effect of symptoms on the association between HRQOL and SOC was also tested. RESULTS: SOC was positively and independently associated with HRQOL (Mental Health: ß = 0.43, 95% confidence interval [CI] = 0.24-0.61, P < 0.001; General Health: ß = 0.41, 95% CI = 0.23-0.59, P < 0.001). The association of SOC with Mental Health scores did not differ by symptoms, whereas its association with General Health was attenuated by symptoms (interaction term of IBDQ by SOC: ß = -0.0082, 95% CI = -0.017 to 0.00064, P = 0.07; that of FIQL by SOC: ß = -0.0052, 95% CI = -0.011 to 0.0010, P = 0.10). CONCLUSIONS: SOC affected mental health independently, and its protective association with general health perception was affected by symptoms. Further research is required to determine the most effective use of SOC in interventions to improve HRQOL in patients with UC.

Trajectory analyses to identify persistently low responders to COVID-19 vaccination in patients with inflammatory bowel disease: a prospective multicentre controlled study, J-COMBAT.

BACKGROUND: The degree of immune response to COVID-19 vaccination in inflammatory bowel disease (IBD) patients based on actual changes in anti-SARS-CoV-2 antibody titres over time is unknown. METHODS: Data were prospectively acquired at four predetermined time points before and after two vaccine doses in a multicentre observational controlled study. The primary outcome was humoral immune response and vaccination safety in IBD patients. We performed trajectory analysis to identify the degree of immune response and associated factors in IBD patients compared with controls. RESULTS: Overall, 645 IBD patients and 199 control participants were analysed. At 3 months after the second vaccination, the seronegative proportions were 20.3% (combination of anti-tumour necrosis factor [TNF]α and thiopurine) and 70.0% (triple combination including steroids), despite that 80.0% receiving the triple combination therapy were seropositive at 4 weeks after the second vaccination. Trajectory analyses indicated three degrees of change in immune response over time in IBD patients: high (57.7%), medium (35.6%), and persistently low (6.7%). In the control group, there was only one degree, which corresponded with IBD high responders. Older age, combined anti-TNFα and thiopurine (odds ratio [OR], 37.68; 95% confidence interval [CI], 5.64-251.54), steroids (OR, 21.47; 95%CI, 5.47-84.26), and tofacitinib (OR, 10.66; 95%CI, 1.49-76.31) were factors associated with persistently low response. Allergy history (OR, 0.17; 95%CI, 0.04-0.68) was a negatively associated factor. Adverse reactions after the second vaccination were significantly fewer in IBD than controls (31.0% vs 59.8%; p < 0.001). CONCLUSIONS: Most IBD patients showed a sufficient immune response to COVID-19 vaccination regardless of clinical factors. Assessment of changes over time is essential to optimize COVID-19 vaccination, especially in persistently low responders.

Development of serological assays to identify Helicobacter suis and H. pylori infections.

Helicobacter suis, hosted by hogs, is the most prevalent gastric non-Helicobacter pylori Helicobacter species found in humans. Recent studies have suggested that H. suis infection has caused many cases of gastric disease, but the transmission route from hogs remains unclear. Diagnostic methods based on H. suis urease activity often yield negative results, and there is no reliable method for diagnosing H. suis infection in clinical practice without gastric biopsy specimens. This study presents the world's first use of whole-bacterial cell ELISA to simultaneously assess H. suis and H. pylori infections. The ELISAs showed high accuracy, with an area under the ROC curve of 0.96, 100% sensitivity, 92.6% specificity, 76.9% positive predictive value, and 100% negative predictive value for the H. suis test, and an area under the ROC curve of 0.92, 88.2% sensitivity, 87.5% specificity, 65.2% positive predictive value, and 96.6% negative predictive value for the H. pylori test.

Artificial intelligence model for analyzing colonic endoscopy images to detect changes associated with irritable bowel syndrome.

IBS is not considered to be an organic disease and usually shows no abnormality on lower gastrointestinal endoscopy, although biofilm formation, dysbiosis, and histological microinflammation have recently been reported in patients with IBS. In this study, we investigated whether an artificial intelligence (AI) colorectal image model can identify minute endoscopic changes, which cannot typically be detected by human investigators, that are associated with IBS. Study subjects were identified based on electronic medical records and categorized as IBS (Group I; n = 11), IBS with predominant constipation (IBS-C; Group C; n = 12), and IBS with predominant diarrhea (IBS-D; Group D; n = 12). The study subjects had no other diseases. Colonoscopy images from IBS patients and from asymptomatic healthy subjects (Group N; n = 88) were obtained. Google Cloud Platform AutoML Vision (single-label classification) was used to construct AI image models to calculate sensitivity, specificity, predictive value, and AUC. A total of 2479, 382, 538, and 484 images were randomly selected for Groups N, I, C and D, respectively. The AUC of the model discriminating between Group N and I was 0.95. Sensitivity, specificity, positive predictive value, and negative predictive value of Group I detection were 30.8%, 97.6%, 66.7%, and 90.2%, respectively. The overall AUC of the model discriminating between Groups N, C, and D was 0.83; sensitivity, specificity, and positive predictive value of Group N were 87.5%, 46.2%, and 79.9%, respectively. Using the image AI model, colonoscopy images of IBS could be discriminated from healthy subjects at AUC 0.95. Prospective studies are needed to further validate whether this externally validated model has similar diagnostic capabilities at other facilities and whether it can be used to determine treatment efficacy.

Colonic TRPV4 overexpression is related to constipation severity.

BACKGROUND: Chronic constipation is prevalent and involves both colon sensitivity and various changes in intestinal bacteria, particularly mucosa-associated microflora. Here we examined regulatory mechanisms of TRPV4 expression by co-culturing colon epithelial cell lines with intestinal bacteria and their derivatives. We also investigated TRPV4 expression in colon epithelium from patients with constipation. METHODS: Colon epithelial cell lines were co-cultured with various enterobacteria (bacterial components and supernatant), folate, LPS, or short chain fatty acids. TRPV4 expression levels and promoter DNA methylation were assessed using pyrosequencing, and microarray network analysis. For human samples, correlation coefficients were calculated and multiple regression analyses were used to examine the association between clinical background, rectal TRPV4 expression level and mucosa-associated microbiota. RESULTS: Co-culture of CCD841 cells with P. acnes, C. perfringens, or S. aureus transiently decreased TRPV4 expression but did not induce methylation. Co-culture with clinical isolates and standard strains of K. oxytoca, E. faecalis, or E. coli increased TRPV4 expression in CCD841 cells, and TRPV4 and TNF-alpha expression were increased by E. coli culture supernatants but not bacterial components. Although folate, LPS, IL-6, TNF-alpha, or SCFAs alone did not alter TRPV4 expression, TRPV4 expression following exposure to E. coli culture supernatants was inhibited by butyrate or TNF-alphaR1 inhibitor and increased by p38 inhibitor. Microarray network analysis showed activation of TNF-alpha, cytokines, and NOD signaling. TRPV4 expression was higher in constipated patients from the terminal ileum to the colorectum, and multiple regression analyses showed that low stool frequency, frequency of defecation aids, and duration were associated with TRPV4 expression. Meanwhile, incomplete defecation, time required to defecate, and number of defecation failures per 24 h were associated with increased E. faecalis frequency. CONCLUSIONS: Colon epithelium cells had increased TRPV4 expression upon co-culture with K. oxytoca, E. faecalis, or E. coli supernatants, as well as TNFα-stimulated TNFαR1 expression via a pathway other than p38. Butyrate treatment suppressed this increase. Epithelial TRPV4 expression was increased in constipated patients, suggesting that TRPV4 together with increased frequency of E. faecalis may be involved in the pathogenesis of various constipation symptoms.

Factors, Including Clinical Trial Eligibility, Associated with Induction of Third-Line Treatment for Advanced Gastric Cancer.

INTRODUCTION: Third-line chemotherapy has been suggested to improve survival in patients with gastric cancer. This study aimed to identify factors associated with the induction of third-line chemotherapy for advanced gastric cancer, focusing on patient eligibility for clinical trial. METHODS: We retrospectively analyzed 335 patients treated for unresectable or recurrent gastric cancer between April 2009 and May 2020. The patients were grouped into those that met the key eligibility criteria for clinical trial (136 patients, 40.6%) and those that did not (199 patients, 59.4%) before receiving first-line chemotherapy. RESULTS: The overall survival (OS) was 16.8 months (95% CI: 14.0-19.6) and 9.3 months (95% CI: 7.8-11.0) in the eligible and ineligible group, respectively. Multivariate analyses to identify the risk factors associated with the induction of third-line chemotherapy revealed ineligibility of clinical trial (OR 1.95; 95% CI: 1.15-3.31), number of metastatic sites (OR 1.99; 95% CI: 1.23-3.22), low albumin concentration (OR 2.24; 95% CI: 1.14-4.38), and a lack of complete or partial response to first-line treatment (OR 1.85; 95% CI: 1.05-3.26). Indeed, in responders to first-line treatment for ineligible patients, the median OS was 17.7 months (95% CI: 10.6-27.9), respectively. CONCLUSIONS: Treatment outcomes were different for those eligible for clinical trials and those who were not. However, this study suggested that patients who responded to first-line treatment have more favorable prognosis when treated with salvage chemotherapy, even if they were deemed ineligible for clinical trials.

Methylation silencing of ULK2 via epithelial-mesenchymal transition causes transformation to poorly differentiated gastric cancers.

BACKGROUND: Diffuse-type gastric cancers (DGC) typically have a poor prognosis related to their invasion and metastasis, in which the epithelial-mesenchymal transition (EMT) is the initiation step. ULK2 plays a role in the autophagy initiation, which might provide a survival advantage in cancer cells. Although knock-down of ULK2 reportedly induces autophagy and EMT in a lung cancer cell line, the mechanism of EMT via the down-regulation of ULK2, as well as its clinical significance, remains yet unclear. The present study, therefore, aims at clarifying this mechanism and its clinical significance in gastric cancers. METHODS: We examined ULK2 mRNA expression in gastric cancer tissues and normal gastric tissues of healthy people. The effects of knock-downed ULK2 were examined in two gastric cancer cells, which were investigated in terms of their gene expression changes by the mRNA microarray. RESULTS: ULK2 was strongly expressed in intestinal-type cancers but was scarcely expressed in DGC by immunohistochemical staining. Furthermore, we found that ULK2 was methylated in DGC and was unmethylated in corresponding adjacent normal tissues. Then, we validated whether knock-down of ULK2 could induce autophagy, cell migration, and EMT in NUGC3 and MKN45 cells. Using mRNA microarray analysis, we confirmed that knock-down of ULK2 changed expressions of oncogenic genes associated with cell migration and EMT. Autophagy inhibitor suppressed cell migration and EMT induced by knock-down of ULK2 in NUGC3 and MKN45. CONCLUSION: Methylation silencing of ULK2 could induce cell migration and EMT by means of autophagy induction, causing transformation to poorly differentiated cancers.

Bilateral Serous Retinal Detachment Associated with a Mitogen-activated Protein KinaseKinase Inhibitor in a Patient with BRAF-mutant Colorectal Cancer.

We herein report a 73-year-old woman with BRAF V600E-mutated colon cancer treated with encorafenib plus cetuximab with binimetinib as standard salvage therapy for patients with advanced colorectal cancer. She developed bilateral serous retinal detachment the next day, and the regimen was discontinued, resulting in complete resolution by the third day. Doublet therapy without binimetinib was initiated along with a weekly ophthalmologic examination for 10 weeks without recurrence of retinal detachment. Thus, binimetinib was presumed to have been the cause of the retinal detachment. This clinical course suggests the need for close monitoring of patients for vision impairment and close collaboration with ophthalmologists.

Protein-losing Enteropathy Complicated with Primary Intestinal Follicular Lymphoma.

Protein-losing enteropathy (PLE) is a rare syndrome characterized by hypoproteinemia due to gastrointestinal (GI) protein loss. Primary intestinal follicular lymphoma (PIFL), a specific variant of follicular lymphoma with essential only GI involvement, has not been reported as an etiology of PLE. We herein report a case of PLE complicated with PIFL that was successfully treated with rituximab, resulting in rapid improvement of PLE and a complete response of PIFL. Macroscopic findings of ulcerative lesions with diffuse involvement, which were precisely described by capsule and double-balloon enteroscopy at the diagnosis, also improved following the treatment. This case provides a clue suggesting factors that promote PLE in PIFL.

Intensive surveillance endoscopy for multiple gastrointestinal tumors in a patient with constitutional mismatch repair deficiency: case report.

BACKGROUND: Constitutional mismatch repair deficiency (CMMRD) is an extremely rare autosomal recessive hereditary disease characterized by the absence of mismatch repair gene activity from birth, which results in brain tumors, colonic polyposis, gastrointestinal cancers, and lymphomas later in life. An aggressive approach, including colectomy or proctocolectomy, is recommended for the treatment of colorectal cancer. Additionally, partial colectomy with subsequent endoscopic surveillance may be an alternative strategy due to poor patient's condition, although there is no evidence of surveillance endoscopy after partial colectomy for CMMRD. CASE PRESENTATION: A 13-year-old male patient with a history of T-lymphoblastic lymphoma underwent total gastrointestinal endoscopy, which revealed rectal cancer, colorectal polyposis, and duodenal adenoma. Differential diagnosis included constitutional mismatch repair deficiency according to its scoring system and microsatellite instability, and subsequent germline mutation testing for mismatch repair genes confirmed the diagnosis of constitutional mismatch repair deficiency based on a homozygous mutation in mutS homolog 6 (MSH6). The patient and his family refused colectomy due to the high risk of malignancies other than colorectal cancer, which could require radical surgery. Therefore, the patient underwent low anterior resection of the rectosigmoid colon for rectal cancer and intensive surveillance endoscopy for the remaining colon polyposis. During the 3-year period after initial surgery, 130 polyps were removed and the number of polyps gradually decreased during 6-months interval surveillance endoscopies, although only one polyp was diagnosed as invasive adenocarcinoma (pT1). CONCLUSIONS: Our experience of short surveillance endoscopy illustrates that this strategy might be one of options according to patient's condition.

Endoscopic Ultrasound-guided Fine Needle Aspiration for the Diagnosis of Duodenal Stenosis Due to Urothelial Carcinoma.

Upper tract urothelial carcinoma (UTUC) initially presents with hematuria and hydronephrosis. We report a case of UTUC presenting with initial findings of duodenal stenosis before the appearance of hydronephrosis. A 59-year-old man presented with upper abdominal symptoms on his initial visit. Esophagogastroduodenoscopy (EGD) revealed circumferential stenosis at the descending part of the duodenum. However, the underlying cause of duodenal stenosis was unknown as repeated histopathological examinations of endoscopic biopsy specimens showed no specific findings. We then performed endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of the thickened duodenal wall, and successfully diagnosed duodenal metastasis of UTUC. EUS-FNA is an effective diagnostic method in cases in which the cause of duodenal stenosis is unknown.

Small intestinal mucosal injury and its risk factors in patients with gastrointestinal cancer who developed complicated fluoropyrimidine-induced diarrhea.

BACKGROUND: Diarrhea is a common adverse event of fluoropyrimidine-based chemotherapy. However, limited data are available on the frequency and risk factors of complicated chemotherapy-induced diarrhea (CID) and small intestinal mucosal damage. In this current study, we aimed to determine the incidence of complicated CID and mucosal injury among patients with complicated CID receiving fluoropyrimidine via small bowel capsule endoscopy (CE) and determined baseline risk factors associated with complicated CID. METHODS: In total, 536 patients with advanced or recurrent gastrointestinal cancer who received fluoropyrimidine-based chemotherapy were retrospectively analyzed. Diarrhea was evaluated using the Common Terminology Criteria for Adverse Events version 4. Complicated CID was defined according to the American Society of Clinical Oncology guidelines. To evaluate small intestinal mucosal injury in patients with complicated CID, CE was performed. Multivariate analysis was performed to identify risk factors for complicated CID. RESULTS: Total number of 32 (6%) patients developed complicated CID. Complicating symptoms were noted in 25 (78%) patients, with cramping, vomiting, and sepsis being observed in 15 (60%), 8 (32%), and 3 (12%) patients, respectively. Among the 13 patients who underwent CE, 11 (85%) showed abnormal findings. Multivariate analysis revealed that oral fluoropyrimidine administration was a risk factor for complicated CID (odds ratio 2.95; 95% confidence interval 1.06-8.19). CONCLUSIONS: Despite the relatively low incidence of complicated CID, mucosal injury of small intestine was common in patients with complicated fluoropyrimidine-induced diarrhea and oral fluoropyrimidine was an independent risk factor.

Factors correlated with drug use for constipation: perspectives from the 2016 open Japanese National Database.

BACKGROUND: The prevalence of chronic constipation is increased in females and with age or environmental (low temperature), racial, socioeconomic, and habitual risk factors. The impact of low outside temperature on constipation drug use remains unclear. Here, we investigated risk factors for constipation drug use by evaluating data from the Japanese National Database. METHODS: This ecological study used the 2016 open Japanese National Database of health insurance claims (prescriptions) to acquire the number of health insurance prescription claims in all 47 prefectures for drugs to relieve constipation, antihypertensives, vasodilators, as well as medical check-ups and questionnaire responses. Internet survey on room temperatures in 2010 were also used. Pearson correlation coefficients (r) between the number of population-based prescriptions for each item were calculated and multiple linear regression analysis (MLR) was performed. RESULTS: Prescriptions for magnesium laxatives significantly correlated with aging (r = 0.58), vasodilators (r = 0.53), being female (r = 0.43), antihypertensives (r = 0.39), and inversely with eating ≤2 h before bedtime (r = - 0.37), total crime rate (r = - 0.33), insomnia (r = - 0.33), and population density (r = - 0.31). Stimulant laxatives (sennoside and picosulfate) were significantly correlated with antihypertensives (r = 0.79), aging (r = 0.69), vasodilators (r = 0.67), and being female (r = 0.56), and were inversely associated with average outside temperature (r = - 0.62), total crime rate (r = - 0.52), average income (r = - 0.51), and 30-min of vigorous exercise (r = - 0.44). Fecal interventions were significantly correlated with aging (r = 0.55) and female (r = 0.59), and inversely correlated with population density (r = - 0.41) and total crime rate (r = - 0.38). MLR analysis identified aging as the only significant risk factor for magnesium laxative use (partial slope [ß] = 1241.0). Female sex and antihypertensives were independent risk factors for stimulant laxative prescriptions (ß = 44,547.0 and 0.2) and average outside temperature and 30-min of vigorous exercise were independent preventive factors (ß = - 616.8 and - 219.1). CONCLUSION: We identified associations of magnesium laxatives with aging, stimulant laxatives with female sex, antihypertensives, low outside temperature and less 30 min of vigorous exercise.

TET repression and increased DNMT activity synergistically induce aberrant DNA methylation.

Chronic inflammation is deeply involved in various human disorders, such as cancer, neurodegenerative disorders, and metabolic disorders. Induction of epigenetic alterations, especially aberrant DNA methylation, is one of the major mechanisms, but how it is induced is still unclear. Here, we found that expression of TET genes, methylation erasers, was downregulated in inflamed mouse and human tissues, and that this was caused by upregulation of TET-targeting miRNAs such as MIR20A, MIR26B, and MIR29C, likely due to activation of NF-κB signaling downstream of IL-1ß and TNF-α. However, TET knockdown induced only mild aberrant methylation. Nitric oxide (NO), produced by NOS2, enhanced enzymatic activity of DNA methyltransferases (DNMTs), methylation writers, and NO exposure induced minimal aberrant methylation. In contrast, a combination of TET knockdown and NO exposure synergistically induced aberrant methylation, involving genomic regions not methylated by either alone. The results showed that a vicious combination of TET repression, due to NF-κB activation, and DNMT activation, due to NO production, is responsible for aberrant methylation induction in human tissues.

Management of Remnant or Recurrent Lesions after Endoscopic Papillectomy.

Endoscopic papillectomy (EP) for ampullary adenomas achieves cure rates ranging from 76% to 90%, and recurrence rates are as high as 33%. If remnant or recurrent lesions after prior EP are endoscopically visible and are not suspected of intraductal extension into the biliary or pancreatic duct, repeated snaring and cutting can be performed until all visible lesions are completely resected. However, endoscopic ablative therapies, particularly argon plasma coagulation, can be attempted for tiny or uncertain remnant and recurrent lesions. In addition, intraductal radiofrequency ablation has recently been attempted for residual intraductal lesions after EP at several institutions. Although still under investigation, it has shown some promise. It might be offered as an alternative to surgery, particularly in patients who are unfit for surgery or those who refuse to undergo surgery.

Distinct DNA methylation targets by aging and chronic inflammation: a pilot study using gastric mucosa infected with Helicobacter pylori.

BACKGROUND: Aberrant DNA methylation is induced by aging and chronic inflammation in normal tissues. The induction by inflammation is widely recognized as acceleration of age-related methylation. However, few studies addressed target genomic regions and the responsible factors in a genome-wide manner. Here, we analyzed methylation targets by aging and inflammation, taking advantage of the potent methylation induction in human gastric mucosa by Helicobacter pylori infection-triggered inflammation. RESULTS: DNA methylation microarray analysis of 482,421 CpG probes, grouped into 270,249 genomic blocks, revealed that high levels of methylation were induced in 44,461 (16.5%) genomic blocks by inflammation, even after correction of the influence of leukocyte infiltration. A total of 61.8% of the hypermethylation was acceleration of age-related methylation while 21.6% was specific to inflammation. Regions with H3K27me3 were frequently hypermethylated both by aging and inflammation. Basal methylation levels were essential for age-related hypermethylation while even regions with little basal methylation were hypermethylated by inflammation. When limited to promoter CpG islands, being a microRNA gene and high basal methylation levels strongly enhanced hypermethylation while H3K27me3 strongly enhanced inflammation-induced hypermethylation. Inflammation was capable of overriding active transcription. In young gastric mucosae, genes with high expression and frequent mutations in gastric cancers were more frequently methylated than in old ones. CONCLUSIONS: Methylation by inflammation was not simple acceleration of age-related methylation. Targets of aberrant DNA methylation were different between young and old gastric mucosae, and driver genes were preferentially methylated in young gastric mucosa.

[Severe interstitial lung disease after one cycle of nivolumab treatment in a patient with advanced gastric cancer].

Although nivolumab was previously reported to cause immune-related interstitial lung diseases (ILD), the detailed characteristics of ILD in gastric cancer are not fully understood. We herein present a rare case of a 66-year-old male with advanced gastric cancer who experienced acute-onset high-grade fever and dyspnea and diagnosed with early-onset ILD during the first cycle of nivolumab. Computed tomography revealed patchy infiltrative shadows and ground-glass opacities. No pathological bacteria were detected in the sputum or the bronchoalveolar lavage, and serous antigens for virus and beta-D-glucan were below the detection limit. These findings were consistent with nivolumab-induced organizing pneumonia. The steroid pulse therapy was effective for ILD, and the patient had complete radiological response, although he relapsed twice during the steroid tapering period.

Seven days triple therapy for eradication of Helicobacter pylori does not alter the disease activity of patients with inflammatory bowel disease.

BACKGROUND/AIMS: The influences of Helicobacter pylori eradication therapy on the disease course of inflammatory bowel disease (IBD) are still unclear. We therefore conducted a multicenter, retrospective cohort study to evaluate the safety of H. pylori eradication therapy for IBD patients. METHODS: IBD patients with H. pylori eradication from 2005 to 2015 (eradication group) and control patients (non-eradication group; 2 paired IBD patients without H. pylori eradication matched with each eradicated patient) were included. IBD exacerbation (increased/additional IBD drug or IBD-associated hospitalization/surgery) and disease improvement based on the physicians' global assessment were investigated at baseline, and at 2 and 6 months after eradication or observation. RESULTS: A total of 429 IBD (378 ulcerative colitis, 51 Crohn's disease) patients, comprising 144 patients in the eradication group and 285 patients in the non-eradication group, were enrolled at 25 institutions. IBD exacerbation was comparable between groups (eradication group: 8.3% at 2 months [odds ratio, 1.76; 95% confidence interval, 0.78-3.92; P=0.170], 11.8% at 6 months [odds ratio, 1.60; 95% confidence interval, 0.81-3.11; P=0.172]). Based on the physicians' global assessment at 2 months, none of the patients in the eradication group improved, whereas 3.2% of the patients in the non-eradication group improved (P=0.019). Multivariate analysis revealed that active disease at baseline, but not H. pylori eradication, was an independent factor for IBD exacerbation during 2 months' observation period. The overall eradication rate was 84.0%-comparable to previous reports in non-IBD patients. CONCLUSIONS: H. pylori eradication therapy does not alter the short-term disease activity of IBD.

Multiple Synchronous Sporadic Gastrointestinal Stromal Tumors in the Stomach and Jejunum.

A 77-year-old patient was admitted to our hospital for the further examination of melena. A computed tomography scan detected two submucosal tumors (SMTs) in the stomach and jejunum. Double-balloon endoscopy revealed the presence of a delle on the jejunal SMT, suggesting that the SMT was the origin of the gastrointestinal bleeding. Both tumors were surgically resected and subsequently diagnosed via histology as gastrointestinal stromal tumors (GISTs). Furthermore, the two GISTs had different mutations in the c-kit gene, suggesting that they were derived from different clonal origins. This report depicts an extremely rare case of multiple synchronous sporadic GISTs in the stomach and jejunum.