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.

Recent steroid use and the relapse risk in ulcerative colitis patients with endoscopic healing.

BACKGROUND: Endoscopic healing (EH) is a therapeutic target in ulcerative colitis (UC). However, even patients who have achieved EH relapse frequently. AIMS: To investigate the association between recent steroid use and relapse risk in UC patients with EH. METHODS: This multi-centre cohort study included 1212 UC patients with confirmed EH (Mayo endoscopic subscore ≤1). We excluded patients with current systemic steroid use or history of advanced therapy. We divided patients into a recent steroid group (last systemic steroid use within 1 year; n = 59) and a non-recent or steroid-naïve group (n = 1153). We followed the patients for 2 years to evaluate relapse, defined as induction of systemic steroids or advanced therapy. We used logistic regression to estimate the odds ratio (OR) of relapse. RESULTS: Relapse occurred in 28.8% of the recent steroid group and 5.6% of the non-recent/steroid-naïve group (multi-variable-adjusted OR 5.53 [95% CI 2.85-10.7]). The risk of relapse decreased with time since the last steroid use: 28.8% for less than 1 year after steroid therapy, 22.9% for 1 year, 16.0% for 2 years and 7.9% beyond 3 years, approaching 4.0% in steroid-naïve patients. (ptrend <0.001). CONCLUSIONS: Even for patients with UC who achieved EH, the risk of relapse remains high following recent steroid therapy. Physicians need to consider the duration since last steroid use to stratify the relapse risk in UC patients with EH.

Symptomatic duodenal intramural hematoma caused by weight training: a report of two cases.

Symptoms of traumatic duodenal intramural hematoma, a rare disease caused by trauma, blood disease, or antithrombotic therapy, can include abdominal pain. Case 1 is that of a 35-year-old man at a gym who dropped a 100 kg barbell on his abdomen. It was diagnosed as a duodenal obstruction caused by a traumatic intestinal wall hematoma. In Case 2, a 16-year-old male adolescent performing deadlift training at a gym had subsequent abdominal pain. It was diagnosed as intestinal wall hematoma. Both patients improved with conservative treatment. Malignancy is sometimes suspected from imaging findings. Detailed patient history and imaging studies can avoid unnecessary surgery.

Role of advanced endoscopy in the management of inflammatory digestive diseases (pancreas and biliary tract).

The progress of endoscopic diagnosis and treatment for inflammatory diseases of the biliary tract and pancreas have been remarkable. Endoscopic ultrasonography (EUS) and EUS-elastography are used for the diagnosis of early chronic pancreatitis and evaluation of endocrine and exocrine function in chronic pancreatitis. Notably, extracorporeal shock wave lithotripsy and electrohydraulic shock wave lithotripsy have improved the endoscopic stone removal rate in patients for whom pancreatic stone removal is difficult. Studies have reported the use of self-expanding metal stents for stent placement for pancreatic duct stenosis and EUS-guided pancreatic drainage for refractory pancreatic duct strictures. Furthermore, EUS-guided drainage using a double-pigtailed plastic stent has been performed for the management of symptomatic pancreatic fluid collection after acute pancreatitis. Recently, lumen-apposing metal stents have led to advances in the treatment of walled-off necrosis after acute pancreatitis. EUS-guided biliary drainage is an alternative to refractory endoscopic biliary drainage and percutaneous transhepatic biliary drainage for the treatment of acute cholangitis. The placement of an inside stent followed by switching to uncovered self-expanding metal stents in difficult-to-treat cases has been proposed for acute cholangitis by malignant biliary obstruction. Endoscopic transpapillary gallbladder drainage is an alternative to percutaneous transhepatic gallbladder drainage for severe and some cases of moderate acute cholecystitis. EUS-guided gallbladder drainage has been reported as an alternative to percutaneous transhepatic gallbladder drainage and endoscopic transpapillary gallbladder drainage. However, it is important to understand the advantages and disadvantages of each drainage method and select the optimal drainage method for each case.

Risk Factors for Developing Metachronous Superficial Gastric Epithelial Neoplasms after Endoscopic Submucosal Dissection.

Background: Although endoscopic submucosal dissection (ESD) provides a high rate of curative resection, the remaining gastric mucosa after ESD is at risk for metachronous superficial gastric epithelial neoplasms (MSGENs). It leaves room for risk factors for developing MSGENs after ESD. This study aimed to identify clinicopathological risk factors for the occurrence of MSGENs, and to evaluate the association of Helicobacter pylori (H. pylori) with the MSGENs. Methods: We conducted a retrospective cohort study including 369 patients with 382 lesions that underwent ESD for adenoma/early gastric cancer. Results: Twenty-seven MSGENs occurred. The subjects were divided into MSGEN and not-MSGEN groups. There was a significantly higher frequency of histological intestinal metaplasia (HIM) and initial neoplasm location in the upper or middle parts (INUM) in the MSGEN group. The HIM and INUM groups had a significantly higher cumulative incidence of MSGENs. We compared 27 patients from the MSGEN group and 27 patients from the not-MSGEN group that were matched to the MSGEN group for variables including HIM and INUM. There was a significantly higher frequency of the spontaneous disappearance of H. pylori in the MSGEN group. Conclusions: HIM, INUM, and the spontaneous disappearance of H. pylori may be clinicopathological risk factors for developing MSGENs after ESD.

Acute Pancreatitis Leading to the Diagnosis of Presymptomatic Crohn's Disease: A Pediatric Case Report.

A 14-year-old boy presented with fever and abdominal pain and was diagnosed with acute pancreatitis based on computed tomography findings. The patient had neither diarrhea nor bloody stool but was diagnosed with microcytic anemia. Endoscopic examination revealed a cobblestone pattern and longitudinal ulcer scars in the jejunum. However, no abnormal findings were observed in the ileum or colon. Endoscopic ultrasound-guided fine-needle aspiration was performed from pancreatic body-tail. Pathological examination revealed no evidence of autoimmune pancreatitis (AIP). It was unclear from pathological examination whether idiopathic pancreatitis had self-limitedly improved or whether it was AIP localized to the pancreatic head. The patient was diagnosed with asymptomatic small-bowel Crohn's disease (CD), which may have been two unrelated events of acute pancreatitis. Acute pancreatitis may precede a diagnosis of inflammatory bowel disease. CD with only jejunal involvement (Montreal classification L4) is extremely rare, and we were able to diagnose it early.

Risk Factors for Stoma Outlet Obstruction after Proctocolectomy for Ulcerative Colitis.

Objectives: Stoma outlet obstruction (SOO) occurs with an incidence of approximately 40% after proctocolectomy for Ulcerative colitis (UC) with diverting ileostomy. This study aimed to identify the risk factors for SOO after proctocolectomy with diverting ileostomy for patients with UC. Methods: We reviewed the data of 68 patients with UC who underwent proctocolectomy and diverting ileostomy between April 2006 and September 2021. These cases were analyzed on the basis of clinicopathological and anatomical factors. SOO was defined as small bowel obstruction displaying symptoms of intestinal obstruction, such as abdominal distention, abdominal pain, insertion of a tube through the stoma. Results: The study included 38 (56%) men and 30 (44%) women with a median age of 42 years (range, 21-80). SOO categorized as at least Clavien-Dindo grade II occurred in 11 (16%) patients. Six patients required earlier stoma closure than scheduled. Compared with patients without SOO, patients with SOO had a significantly higher total steroid dose from the onset of UC to surgery (p = 0.02), a small amount of intraabdominal fat (p = 0.04), and a higher rate of laparoscopic surgery (p < 0.01). Conclusions: A high preoperative steroid dose, a small amount of intraabdominal fat and laparoscopic surgery were identified as risk factors for SOO. Early detection and treatment for SOO are important for patients at risk.

White Blood Cell Counts and Future Relapse in Ulcerative Colitis under Low-Dose Thiopurine Treatment in Real-World Practice: A 3-Year Japanese Multi-Center Retrospective Cohort Study.

Introduction: Whether white blood cell (WBC) counts are predictors for the effectiveness of thiopurine treatment in ulcerative colitis (UC) has been inconclusive in previous studies with small sample sizes. We investigated the association between WBC counts and future relapses in UC patients in a large-scale multi-center study. Methods: This retrospective cohort study enrolled a total of 723 UC patients in remission from 33 hospitals and followed up for 3 years. Relapse was defined as a need for treatment intensification. The risk of relapse was compared among patients with the baseline WBC counts <3,000/µL (N = 31), 3,000-4,000/µL (N = 167), 4,000-5,000/µL (N = 241), and ≥5,000/µL (N = 284) using a Cox regression model analysis. Moreover, exploratory analyses were conducted to identify other factors predicting relapse. Results: During a median follow-up period of 1,095 (interquartile range, 1,032-1,119) days, relapse occurred in 17.2% (125/723). In a crude analysis, WBC counts were not associated with relapse; hazard ratios (HRs) (95% confidence interval [CI]) were 1.50 (0.74-3.06), 1.02 (0.66-1.59), and 0.67 (0.43-1.05) in WBC <3,000/µL, 3,000-4,000/µL, and 4,000-5,000/µL groups, respectively (WBC ≥5,000/µL group, as reference). Multivariable-adjusted analyses showed similar results; HRs (95% CI) were 1.21 (0.59-2.49), 1.08 (0.69-1.69), and 0.69 (0.44-1.07), in <3,000/µL, 3,000-4,000/µL, and 4,000-5,000/µL groups, respectively. In the exploratory analyses, thiopurine use <1 year and a mean corpuscular volume <90 fL were predictors for relapse. Discussion/Conclusion: WBC counts were not predictors for future relapses in patients with UC treated with thiopurine as a maintenance therapy.

Hereditary Diffuse Gastric Cancer Treated by Prophylactic Total Gastrectomy.

We herein report a rare case of hereditary diffuse gastric cancer in a Japanese man. A 41-year-old man underwent esophagogastroduodenoscopy which revealed a small gastric erosion. Biopsy specimens showed signet ring cell carcinoma, and endoscopic submucosal dissection was performed. The patient's elder sister had died of gastric cancer at 38 years old. Considering the family history, a genetic test was conducted and revealed a CDH1 germline mutation. Although no carcinomatous lesion was detected endoscopically, prophylactic total gastrectomy was performed. The resection specimen showed seven microlesions of signet ring cell carcinoma confined to the lamina propria mucosae.

Investigating COVID-19 Pandemic Effects on Acute Pancreatitis Development-From the Perspective of Alcohol Sales (Consumption) in a Japanese Regional Hospital.

[Aim and Background] People's lifestyles changed considerably due to the coronavirus disease 2019 (COVID-19) pandemic. The number of patients with acute pancreatitis (AP) can be expected to decrease as alcohol consumption decreases. This study was conducted to assess COVID-19 pandemic effects on AP patients in a Japanese regional hospital. [Methods] Based on the first and second states of emergency declarations in Tochigi Prefecture, the survey periods were set as follows: period A, 16 April-14 May; period B, 15 May-13 January; period C, 14 January-7 February; and period D, 8 February-15 April. Using data acquired in 2017, 2018, 2019, and 2020, we retrospectively reviewed the number of patients admitted to our hospital with a diagnosis of AP, and their clinical characteristics. [Results] According to a National Tax Agency survey, the average alcohol sales per adult in Tochigi Prefecture were 71.3 L in 2017 before the pandemic, and 64.0 L in 2021 under the pandemic. The number of AP patients in 2020 was 38% lower than in 2017. Comparing 2017 with 2020, the number of alcoholic AP patients was lower in 2020 (p = 0.007). [Conclusions] The findings suggest that COVID-19-pandemic-related lifestyle changes contributed to the decrease in AP patients.

Proposal and Validation of New Diagnostic Criteria for Diagnostic Weights of Endoultrasonographic Findings for Early Chronic Pancreatitis.

[Background and study aim] A commonly applied method for diagnosing chronic pancreatitis (CP) uses endoscopic ultrasonography (EUS), assigning weights to each EUS diagnostic finding. It is the Rosemont classification (RC). In 2019, to improve EUS diagnostic specificity, Japanese diagnostic criteria for early chronic pancreatitis (ECP) were revised. Nevertheless, the criteria use no weighting of EUS diagnostic findings, as the RC does. This study was undertaken to propose diagnostic criteria that would weight each EUS finding of ECP and that would be more specific than the RC. [Methods] By EUS of the pancreas, 773 patients underwent detailed observation from January 2018 to March 2019 at our institution. An expert finalized all cases when patients were diagnosed. Using data from the medical records, 97 consecutive patients with EUS diagnostic findings of ECP based on the Japanese diagnostic criteria of ECP2009 (JDCECP2009) were selected. The definition under the RC of "Indeterminate for CP" was equivalent to ECP. Each case was diagnosed using (1) JDCECP2009 and (2) the Japanese diagnostic criteria of ECP2019 (JDCECP2019). Moreover, the four diagnostic EUS findings in JDCECP2019 were applied to the RC, weighted (modified-JDCECP2019), and subsequently compared with the earlier diagnostic criteria. As Modified-JDCECP2019, we suggested (3) RC-A-the current four items scored related to the RC, and (4) RC-B-the five items scored by dividing lobularity with and without honeycombing. [Results] Diagnoses produced based on each criterion were normal: ECP = (1) 20:77, (2) 46:51, (3) 52:42, and (4) 60:35. [Conclusions] Modified-JDCECP2019 may provide EUS diagnoses for ECP with higher specificity.

A case in which the tip of a plastic stent placed to prevent recurrence of walled-off necrosis penetrated the bile duct and formed a stent-stone complex.

A woman in her 60s underwent endoscopic sphincterotomy for choledocholithiasis. Unfortunately, post-endoscopic retrograde cholangiopancreatography pancreatitis occurred. In addition, huge walled-off necrosis (WON) appeared as a late complication. For the infected WON, endoscopic ultrasound-guided fistuloplasty and endoscopic necrosectomy were performed, and a double pigtail plastic stent (PS) (7Fr, 7 cm) was placed to prevent a recurrence. Plain computed tomography conducted two years later showed that the stent implanted for WON had deviated. The distal end of the stent was found to have migrated into the bile duct. In addition, common bile duct stones with stents as nuclei were observed. Upon performing endoscopic retrograde cholangiography, it was revealed that the stent tip perforated the distal bile duct just above the papilla. After removal of the stent using grasping forceps, we made an incision between the duodenal - bile duct fistula and bile duct orifice using a sphincterotome. Then, the stone was removed by a balloon catheter. Although such late adverse events are rare occurrences, placement of long-term PS after treatment of WON should be followed up regularly with imaging examination, and if there is no recurrence for several months, removal of the PS at that point may be considered.

Guide Wire Selection (Straight vs. Angled) in Endoscopic Retrograde Cholangiopancreatography Using a Normal Contrast Catheter Performed by a Trainee: A Single-Center Prospective Randomized Controlled Cross-Over Study.

INTRODUCTION: Wire-guided cannulation (WGC) during endoscopic retrograde cholangiopancreatography (ERCP) is a selective biliary cannulation technique aimed at improving the successful selective biliary cannulation rate and reducing the rate of post-ERCP pancreatitis (PEP) incidence. This study aimed to evaluate the effectiveness of angled-tip guidewires (AGW) vs. straight-tip guidewires (SGW) for biliary cannulation via WGC by a trainee. METHODS: We conducted a prospective, single-center, open-labeled, randomized, and controlled trial. Fifty-seven patients were enrolled in this study and assigned randomly to two groups (Group A to S and Group S to A). In this study, we started selective biliary cannulation via WGC with an AGW or an SGW for 7 min. If cannulation was unsuccessful, the other guidewire was used, and cannulation was continued for another 7 min (cross-over method). RESULTS: The selective biliary cannulation success rate over 14 min was significantly higher with an AGW compared with an SGW over 14 min (57.8% vs. 34.3%, p = 0.04) and for the second 7-min segment (36.4% vs. 0%, p = 0.04). No significant difference was found for adverse events such as pancreatitis between the two guidewires. CONCLUSIONS: Our results suggest that an AGW is recommended for WGC performed by a trainee.

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.

Natural History of Small Gastric Subepithelial Lesions Less than 20 mm: A Multicenter Retrospective Observational Study (NUTSHELL20 Study).

BACKGROUND AND AIM: Small gastric subepithelial lesions (SELs) are sometimes encountered in daily esophagogastroduodenoscopy (EGD) practice, but whether once-annual or twice-annual endoscopy can provide sufficient follow-up remains unclear. Because follow-up based on small-SEL characteristics is important, this study clarified the natural history of gastric SELs less than 20 mm. METHODS: This retrospective multicenter observation study conducted at 24 Japanese hospitals during April 2000 to March 2020 examined small gastric SELs of ≤20 mm diameter. The primary outcome was the rate of size increase of those SELs detected using EGD, with growth times assessed irrespective of SEL pathological diagnoses. RESULTS: We examined 824 cases with tumors of 1-5 mm diameter in 298 (36.2%) cases, 6-10 mm in 344 (41.7%) cases, 11-15 mm in 112 (13.6%) cases, and 16-20 mm in 70 (8.50%) cases. An increase of small gastric SELs was observed in 70/824 patients (8.5%). The SELs larger than 6 mm increased, even after 10 years. No-change and increasing groups had no significantly different malignant findings at diagnosis. In cases of gastrointestinal stromal tumors (GISTs), internal cystic change in endoscopic ultrasound (EUS) is a risk factor for an increased tumor size. The predictive tumor growth cutoff size at initial diagnosis was 13.5 mm. CONCLUSIONS: Small gastric SELs less than 20 mm have an approximately 8.5% chance of increase. Predictive markers for GIST growth are tumor size ≥13.5 mm and internal cystic change in EUS.

Size reduction of gastric fundic gland polyposis by de-escalation of acid-suppressive therapy.

The patient, a 73-year-old woman, had been taking acid-suppressive therapy for refractory reflux esophagitis for 10 years. A potassium-competitive acid blocker was administered to strengthen acid-suppressive therapy for worsening symptoms of gastroesophageal reflux disease. Esophagogastroduodenoscopy showed an increase in the number and size of fundic gland polyposis (FGPs). When acid-suppressive therapy was changed from potassium-competitive acid blocker to proton pump inhibitor, the FGPs showed reduced size 1 year later. Furthermore, when acid-suppressive therapy was changed from proton pump inhibitor to histamine-2 receptor antagonist, FGPs were even smaller after 1 and 2 years. The patient, who had no flare-up of gastroesophageal reflux disease symptoms, continues to be treated medically with histamine-2 receptor antagonist. This case report describes changes in endoscopic findings of a patient with FGPs caused by acid-suppressive therapy for refractory gastroesophageal reflux disease.

A case of obstructive jaundice caused by metastasis of breast cancer to the intra/extrahepatic bile duct.

A 38-year-old woman was admitted to our hospital for a detailed examination of jaundice. Three years before, she had undergone a right total mastectomy and axillary lymph node dissection of her right breast because of cancer. Histopathological evaluation revealed invasive ductal carcinoma. Postoperatively, because multiple bone metastases were found, she underwent chemoradiotherapy. Endoscopic retrograde cholangiopancreatography was performed, which revealed widespread multiple stenoses with a smooth surface from the intrahepatic to the extrahepatic bile duct. A transpapillary biliary biopsy was performed. Histopathological examination revealed adenocarcinoma extending into the subepithelium of the bile duct. The obtained cancer cells were similar to those of the earlier invasive breast cancer. This rare case demonstrates bile duct metastasis of breast cancer with specific endoscopic retrograde cholangiopancreatography findings.

Diagnosing chronic pancreatitis by endoscopic ultrasound assessing the association between ultrasound and pathological findings: A narrative review.

Endoscopic ultrasound (EUS) is widely recognized for its non-invasiveness and for its usefulness in chronic pancreatitis (CP) diagnosis, including early CP. Although it is desirable to obtain a definitive diagnosis of CP by tissue sampling with EUS-guided fine needle aspiration, histopathological changes in CP are heterogeneous in terms of the extent and the distribution of lesions. Therefore, histopathological diagnosis of appropriate tissue sampling by EUS-fine needle aspiration is expected to be difficult. Furthermore, it is virtually impossible to match EUS images with pathological sections, making direct contrast between EUS findings and pathology difficult. This narrative review presents a discussion of the diagnosis of CP/early CP by EUS, particularly assessing the association between ultrasound and pathological findings. Recently, the histological corroboration and correlation of EUS findings related to CP have been clarified by surgical specimens, including those obtained from animal studies. Furthermore, remarkable advances have occurred in the objective and quantitative diagnosis of pancreatic fibrosis by EUS-elastography. Future technological advances in EUS are expected to improve the accuracy of diagnosis of pancreatic fibrosis at earlier stages.

Advanced Endoscopy for Benign Esophageal Disease: A Review Focused on Non-Erosive Reflux Disease and Eosinophilic Esophagitis.

Advanced endoscopy (AVE) techniques include image-enhanced endoscopy methods, such as narrow-band imaging (NBI), and types of microscopic endoscopy, such as endocytoscopy. In the esophagus, AVE first showed diagnostic utility in the diagnosis of superficial esophageal cancer and was then applied to inflammatory disease. This review focuses on non-erosive reflux disease (NERD) and eosinophilic esophagitis (EoE), which sometimes show no abnormal findings on standard white light endoscopy alone. Studies have demonstrated that advanced endoscopy, including NBI magnification endoscopy and endocytoscopy, improved the diagnostic performance of white-light endoscopy alone for NERD and EoE. In this review, we explain why advanced endoscopy is needed for the diagnosis of these esophageal inflammatory diseases, summarize the study results, and discuss future perspectives.