Search

Background: Patients with inflammatory bowel diseases (IBD) can develop extraintestinal manifestations (EIMs) during the disease course, which sometimes impact their quality of life. Objectives: This study aimed to clarify the prevalence and types of EIMs using a hospital-based IBD cohort in Japan. Methods: A patient cohort with IBD was established in 2019, as participated by 15 hospitals in Chiba Prefecture of Japan. Using this cohort, the prevalence and types of EIMs, which are defined based on previous reports and the Japanese guidelines, were investigated. Results: This cohort enrolled 728 patients, including 542 ulcerative colitis (UC) and 186 Crohn’s disease (CD). Of these patients with IBD, 10.0% were identified with one or more EIMs (57 (10.5%) with UC and 16 (8.6%) with CD). Arthropathy and arthritis were the most common EIM in 23 (4.2%) patients with UC, followed by primary sclerosing cholangitis (PSC) (2.6%). Arthropathy and arthritis were also the most common in patients with CD, but no cases of PSC were observed. EIMs were more frequently observed in patients with IBD treated by specialists than in those treated by non-specialists (12.7% vs. 5.5%, p = 0.011). The incidence of EIMs in patients with IBD was not significantly different over time. Conclusions: The prevalence and types of EIMs in our hospital-based cohort in Japan did not significantly differ from those reported in previous or Western studies. However, the incidence might be underestimated due to the limited ability of non-IBD specialists to discover and describe EIMs in patients with IBD.

This study aimed to investigate the lesion and endoscopist factors associated with unintentional endoscopic piecemeal mucosal resection (uniEPMR) of colorectal lesions ≥ 10 mm. uniEPMR was defined from the medical record as anything other than a preoperatively planned EPMR. Factors leading to uniEPMR were identified by retrospective univariate and multivariate analyses of lesions ≥ 10 mm (adenoma and carcinoma) that were treated with endoscopic mucosal resection (EMR) at three hospitals. Additionally, a questionnaire survey was conducted to determine the number of cases treated by each endoscopist. A learning curve (LC) was created for each lesion size based on the number of experienced cases and the percentage of uniEPMR. Of 2557 lesions, 327 lesions underwent uniEPMR. Multivariate analysis showed that lesion diameter ≥ 30 mm (odds ratio 11.83, 95% confidence interval 6.80–20.60, p

Background and Aims The application of underwater EMR (UEMR) for nonpolypoid superficial nonampullary duodenal epithelial tumors (SNADETs) has not been comprehensively assessed. Therefore, the current study aimed to validate the efficacy of UEMR versus conventional EMR and cap-assisted EMR (EMRC) for SNADETs measuring ≤20 mm. Methods We retrospectively analyzed patients with sporadic nonpolypoid SNADETs measuring ≤20 mm undergoing EMR, EMRC, or UEMR at Chiba University Hospital between May 2004 and October 2020 (EMR, 21 patients and 23 SNADETs; UEMR, 60 patients and 61 SNADETs; EMRC, 45 patients and 48 SNADETs). A weighted logistic regression analysis was performed to analyze outcomes. Univariate and multivariate logistic regression models were used to identify the predictors of RX/1 and piecemeal resection. The recurrence rate of lesions observed ≥12 months after resection was assessed. Results Both UEMR and EMRC had a significantly higher R0 resection rate than EMR. UEMR had significantly lower multiple resection and postbleeding rates than EMR. Only 1 patient (2.1%) who underwent EMRC experienced intraoperative and postoperative perforation. EMR was involved in RX/1 and piecemeal resection. The recurrence rates of EMR, UEMR, and EMRC were 4.3%, 2.0%, and 6.3%, respectively. Conclusions UEMR had significantly higher R0 resection and lower postbleeding rates than EMR. Moreover, it was safer than EMRC and was associated with a lower incidence of recurrences. The significant results of the retrospective analysis suggest a randomized controlled study with adequate numbers needs to be conducted to confirm the superior efficacy of UEMR before it is recommended for primary treatment option for SNADETs measuring ≤20 mm.

BACKGROUND AND AIM The effectiveness of cold snare polypectomy (CSP) for superficial non-ampullary duodenal epithelial tumors (SNADETs) regarding long-term outcomes is not fully clarified. This study aimed to investigate long-term outcomes of CSP for SNADETs. METHODS Patients diagnosed with sporadic SNADETs and treated with CSP at Chiba University Hospital between March 2015 and May 2018 were retrospectively analyzed. Long-term outcomes, short-term outcomes, and adverse events were investigated. RESULTS In total, 35 patients with 46 lesions were included. The en-bloc resection rate was 97.8%. Thirty-seven lesions (80.4%) were diagnosed as adenomatous. The R0 resection rate for adenomatous lesions was 70.3%. Follow-up investigations more than 12 months after CSP were completed for 35 adenomatous lesions (94.6%). The median observation period after CSP was 48 months. One patient whose observation period was only 3 months died from chronic heart failure with cardiac sarcoidosis 6 months after CSP. No patient died from SNADETs. The relapse-free survival rate at 12 months after CSP was 97.1%. One recurrence (2.7%) was observed 12 months after CSP. We removed the recurrence lesion with CSP and cold forceps polypectomy. No new recurrence occurred within the observation period. No perforation or post-operative bleeding occurred for CSP. CONCLUSIONS Cold snare polypectomy for diminutive and small SNADETs is a safe and useful procedure with a high en-bloc resection rate and long-term local control capability.

The genetic characteristics of Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) in the Japanese population is unclear. This study aims to investigate the genetic characteristics from nondysplastic BE (NDBE) to early EAC in Japan. Clinical information was collected. Moreover, the genetic profile of NDBE without concurrent dysplasia, early EAC, and surrounding BE were also investigated using endoscopic biopsy samples and formalin-fixed, paraffin-embedded specimens from Japanese patients by targeted next-generation sequencing. Immunohistochemical staining for p53 was also performed for EAC lesions. Targeted NGS was performed for 33 cases with 77 specimens. No significant difference exists in the NDBE group between the number of putative drivers per lesion in the short-segment Barrett’s esophagus (SSBE) and long-segment Barrett’s esophagus (LSBE) [0 (range, 0–1) vs. 0 (range, 0–1). p = 1.00]. TP53 putative drivers were found in two patients (16.7%) with nondysplastic SSBE. TP53 was the majority of putative drivers in both BE adjacent to EAC and EAC, accounting for 66.7% and 66.7%, respectively. More putative drivers per lesion were found in the EAC than in the NDBE group [1 (range, 0–3) vs. 0 (range, 0–1). p TP53 in the Japanese early EAC were similar to those in western countries. However, TP53 putative drivers were detected even in Japanese patients with nondysplastic SSBE. This is significant because such nondysplastic SSBE might have higher risk of progressing to high-grade dysplasia or EAC. The risks of progression may not be underestimated and appropriate follow-ups may be necessary even in patients with SSBE.Trial registration: This study was registered at the University Hospital Medical Information Network (UMIN000034247).

A patient experienced gastric fundic gland-type hyperplastic polyps, consisting of foveolar epithelium and parietal cells, complicated with chronic bleeding due to long-term treatment with vonoprazan. The patient had progressive anemia, probably caused by bleeding from the polyps. After switching from vonoprazan to a histamine-2 (H2) receptor antagonist, the polyps markedly shrank and the anemia improved. Vonoprazan can produce reversible hyperplastic polyps and anemia. In case of anemia in patients receiving long-term vonoprazan, it is important to consider drug cessation or change to an H2 blocker.

Somatic mutations including the background mucosa in patients with Lugol‐voiding lesions (LVLs) are still not well known. The aim of this study was to evaluate the somatic mutations of the background mucosa in patients with LVLs (Squamous cell carcinoma (SCC), intraepithelial neoplasia (IN), and hyperplasia). Twenty‐five patients with LVLs (9 with SCC, 6 with IN, and 10 with hyperplasia) were included. A targeted sequence was performed for LVLs and background mucosa using an esophageal cancer panel. Each mutation was checked whether it was oncogenic or not concerning OncoKB. In LVLs, TP53 was the most dominant mutation (80%). Furthermore, 72% of TP53 mutations was putative drivers. In background mucosa, NOTCH1 was the most dominant mutation (88%) and TP53 was the second most dominant mutation (48%). Furthermore, 73% of TP53 mutations and 8% of NOTCH1 mutations were putative drivers. Putative driver mutations of TP53 had significantly higher allele frequency (AF) in SCC than in IN and hyperplasia. Conversely, putative driver mutations of NOTCH1 did not have a significant accumulation of AF in the progression of carcinogenesis. Furthermore, in SCC, AF of TP53 mutations was significantly higher in LVLs than in background mucosa, but not in IN and hyperplasia. Regarding NOTCH1, a significant difference was not observed between LVLs and background mucosa in each group. The background mucosa in patients with LVLs already had putative driver mutations such as TP53 and NOTCH1. Of these two genes, TP53 mutation could be the main target gene of carcinogenesis in esophageal SCC. Clinical Trials registry: UMIN000034247., The background mucosa in patients with LVLs already has accumulated gene mutations. Notably, many putative driver mutations were confirmed in TP53 and NOTCH1. The TP53 could be the main target gene of the carcinogenesis in esophageal SCC; this mutation was also found in the background mucosa in high‐risk patients.

Endoscopic treatment is recommended for low-grade dysplasia (LGD), high-grade dysplasia (HGD), and colorectal cancer (CRC) with submucosal (SM) invasion 1000 μm. However, diagnosis of invasion depth requires experience and is often difficult. This study developed and evaluated a novel computer-aided diagnosis (CAD) system to determine whether endoscopic treatment is appropriate for colorectal lesions using only white-light endoscopy (WLE).We extracted 3442 images from 1035 consecutive colorectal lesions (105 LGDs, 377 HGDs, 107 CRCs with SM 1000 μm, 146 CRCs with SM ≥1000 μm, and 300 advanced CRCs). All images were WLE, nonmagnified, and nonstained. We developed a novel CAD system using 2751 images; the remaining 691 images were evaluated by the CAD system as a test set. The capability of the CAD system to distinguish endoscopically treatable lesions and untreatable lesions was assessed and compared with the results from 2 trainees and 2 experts.The CAD system distinguished endoscopically treatable from untreatable lesions with 96.7% sensitivity, 75.0% specificity, and 90.3% accuracy. These values were significantly higher than those from trainees (92.1%, 67.6%, and 84.9%; P .01, .01, and .01, respectively) and were comparable with those from experts (96.5%, 72.5%, and 89.4%, respectively). Trainees assisted by the CAD system demonstrated a diagnostic capability comparable with that of experts.The CAD system had good diagnostic capability for making treatment decisions for colorectal lesions. This system may enable a more convenient and accurate diagnosis using only WLE.

Barrett’s esophagus (BE) is a precursor of esophageal adenocarcinoma (EAC). Therefore, an accurate diagnosis of BE is important for the subsequent follow-up and early detection of EAC. However, the definitions of BE have not been standardized worldwide; columnar-lined epithelium (CLE) without intestinal metaplasia (IM) and/or 1 cm (Group A) and those without IM and/or

Salivary pepsin measurement has been reported to be useful for diagnosing gastroesophageal reflux disease (GERD). This study aimed to clarify the usefulness of salivary pepsin measurement in patients with proton pump inhibitor (PPI)-refractory GERD symptoms without erosive esophagitis.One hundred and two patients were included. Over seven days after terminating PPI treatment, all patients underwent a 24-h pH-impedance test and salivary pepsin measurement. In patients whose main symptoms included laryngopharyngeal symptoms, a hypopharyngeal multichannel intraluminal impedance (HMII) test was performed, whereas in other patients, a conventional combined multichannel intraluminal impedance-pH (MII-pH) test was performed. In the HMII tests, patients were divided into abnormal proximal exposure (APE) and non-APE groups. Salivary pepsin concentrations were compared according to acid exposure time (AET) values and were also compared between the APE and non-APE groups.The median salivary pepsin concentration in patients with AET 6% was significantly higher than that in patients with AET ≤ 6% (345.0 [170.0-469.3] ng/mL vs. 120.0 [97.0-290.1] ng/mL, p 0.01). The sensitivity, specificity, positive predictive value, and negative predictive value of a positive test ( 109 ng/mL) to diagnose patients with AET 6% were 75.0%, 51.3%, 32.1%, and 86.9%, respectively. There was no significant difference between concentrations in the APE group and concentrations in the non-APE group.In patients with PPI-refractory nonerosive reflux disease, salivary pepsin measurement may help diagnose patients who have conclusive evidence of reflux, whereas it is not adequate for identifying patients with APE.

Objective: To gain better understanding of the effects of biologics, we evaluated clinical outcomes in patients with moderate to severe exacerbations of ulcerative colitis (UC).Methods: This retrospective, multicenter study retrieved the entire clinical courses of UC patients who began treatments between 2004 and 2018. All exacerbations and clinical parameters, including treatment details for exacerbations and both remission and re-exacerbation dates, were identified during the observation period. Two different endpoints, the cumulative incidence rates of surgical resection and re-exacerbation, were evaluated separately in moderate to severe exacerbation events.Results: Among 1401 patients, 1626 exacerbation events were determined according to a partial Mayo score (remission: 7). During the observation period, as administration rates of biologics increased, both surgical resection and hospitalization rates decreased, for 959 moderate to severe exacerbation events. We confirmed that biologics significantly reduced the cumulative re-exacerbation rate in moderate to severe exacerbation events during the study period compared with suboptimal therapies (a 0.507-fold decrease risk according to COX regression analysis, P P = 0.606).Conclusions: Biologics may improve remission duration, but these agents had no significant impact in reducing the risk of surgical resection in moderate to severe active UC.

Anti-tumor necrosis factor (TNF)α antibody (ATA) and biologics/molecular targeted agents with other mechanisms (non-ATA) are currently available for refractory ulcerative colitis (UC). However, the knowledge about optimal drug selection after the initial treatment with ATA failure is lacking. This study assessed whether the response to the initial ATA could be a basis for selecting subsequent agents in UC patients.Ulcerative colitis patients treated with ATA or non-ATA as the subsequent biologic after the failure of initial ATA were retrospectively analyzed. The efficacy at 14 weeks was examined according to the response to initial ATA.Of 163 patients treated with the first ATA, the efficacy of subsequent ATA and non-ATA was evaluated in 63 and 36, respectively. Remission and response to subsequent-line therapy, regardless of ATA or non-ATA, were lower in patients with primary nonresponse (PNR) to initial ATA than in patients with efficacy to initial ATA (33.3% vs 69.2%, P 0.01). In patients with PNR to initial ATA, the remission rate with subsequent ATA was significantly lower than with subsequent non-ATA (4.3% vs 26.3%, P = 0.04). In patients who showed efficacy to initial ATA, the remission rate with subsequent ATA was also lower than that with subsequent non-ATA (30.6% vs 56.3%, P = 0.08). PNR with initial ATA was the predictor of PNR to subsequent ATA (odds ratio: 5.62, 95% confidence interval: 1.50-21.7).Non-ATA may be suitable in UC patients as the subsequent biologics regardless of the outcome of the first ATA.

The appropriate selection of endoscopic resection for relatively small superficial nonampullary duodenal adenomas (SNADAs) considering recurrence is not completely clarified. Therefore, this study investigated endoscopic resection utility (EMR, underwater EMR [UEMR], and cap-assisted EMR [EMRC]) for SNADAs from the viewpoint of recurrence and short-term outcomes.We retrospectively analyzed patients with sporadic SNADAs who underwent EMR, UEMR, and EMRC at Chiba University Hospital between May 2004 and March 2020 and were observed for ≥12 months after endoscopic resection (EMR, 34 patients, 36 lesions; UEMR, 54 patients, 55 lesions; and EMRC, 45 patients, 48 lesions). Outcomes were evaluated using weighted logistic regression analysis. The logistic regression analysis was weighted using propensity scores.EMRC showed significantly higher en-bloc and R0 resection rates than EMR. All techniques were equally safe. Only 1 case each of intraoperative perforation and postoperative perforation (in 2 different patients) occurred, which were associated with EMRC. UEMR resulted in higher R0 resection and lower postbleeding rates than EMR. Moreover, patients who underwent UEMR showed no perforation. Median observation period per lesion after endoscopic resection was 84 months (range, 16-199) for patients who underwent EMR, 25 months (range, 12-60) for patients who underwent UEMR, and 63 months (range, 12-180) for patients who underwent EMRC. No significant difference was observed between EMR versus UEMR and between EMR versus EMRC in terms of recurrence (odds ratio, .20 [95% confidence interval, .01-2.86; P = .24] and .78 [95% confidence interval, .09-6.84; P = .82], respectively).Recurrence risk was not different for EMR, UEMR, and EMRC. Therefore, UEMR, a simple and safe procedure, could be the first choice for relatively small SNADAs. With larger prospective studies, UEMR data may turn out to be more robust, corroborating it as the endoscopic modality of choice for certain SNADAs.

This study aimed to prevent missing gastric cancer and point out low-quality images by developing a double-check support system (DCSS) for esophagogastroduodenoscopy (EGD) still images using artificial intelligence. We extracted 12,977 still EGD images from 855 cases with cancer [821 with early gastric carcinoma (EGC) and 34 malignant lymphoma (ML)] and developed a lesion detection system using 10,994 images. The remaining images were used as a test dataset. Additional validation was performed using a new dataset containing 50 EGC and 1,200 non-GC images by comparing the interpretation of ten endoscopists (five trainees and five experts). Furthermore, we developed another system to detect low-quality images, which are not suitable for diagnosis, using 2198 images. In the validation of 1983 images from the 124 cancer cases, the DCSS diagnosed cancer with a sensitivity of 89.2%, positive predictive value (PPV) of 93.3%, and an accuracy of 83.3%. EGC was detected in 93.2% and ML in 92.5% of cases. Comparing with the endoscopists, sensitivity was significantly higher in the DCSS, and the average diagnostic time was significantly shorter using the DCSS than that by the trainees. The sensitivity, specificity, PPV, and accuracy in detecting low-quality images were 65.8%, 93.1%, 79.6%, and 85.2% for “Blur” and 57.8%, 91.7%, 82.2%, and 78.1% for “Mucus adhesion,” respectively. The DCSS showed excellent capability in detecting lesions and pointing out low-quality images.

BACKGROUND AND AIM Cold snare polypectomy (CSP) is a safe treatment for colorectal adenomas. However, the R0 resection rate is not sufficiently high because of inadequate resection of muscularis mucosa. We hypothesized that CSP in an underwater environment could improve this procedure by helping to safely achieve resection containing the muscularis mucosa. We have named this procedure underwater cold snare polypectomy (UCSP). We aimed to investigate the efficacy and safety of UCSP for colorectal adenomas. METHODS Between May 2017 and April 2018, patients diagnosed with colorectal adenomas

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

The infliximab biosimilar CT-P13 was the first biosimilar drug targeting tumor necrosis factor-α. However, its efficacy and safety in real-world clinical situations have remained insufficient. Therefore, we aimed to verify the efficacy and safety of CT-P13 in bio-naïve patients with Crohn’s disease. This retrospective multicenter study compared the remission rate at week 54 between patients with Crohn’s disease treated with originator infliximab or CT-P13. Endoscopic and laboratory findings were assessed in both groups. A total of 184 (156 originator and 28 CT-P13) patients were analyzed. Of these, 138 originator users and 19 biosimilar users completed 54-week administration. The clinical remission rates in patients taking originator infliximab of CT-P13 at week 54 were 92.5% and 100%, respectively. The endoscopic scores of each group significantly decreased from baseline at week 54 in both groups, and the mucosal healing rate at week 54 was 53% and 64%, respectively. Laboratory data significantly improved from baseline to week 14 and 54 in both groups. Adverse events were observed more frequently in the CT-P13 group ( 25% vs. 4.5%, p = 0.0015). The efficacy of CT-P13 were comparable with those of originator infliximab in bio-naïve patients with Crohn’s disease evaluated by clinical, endoscopic, and laboratory findings.

In 2020, Olympus Medical Systems Corporation introduced the Texture and Color Enhancement Imaging (TXI) as a new image-enhanced endoscopy. This study aimed to evaluate the visibility of neoplasms and mucosal atrophy in the upper gastrointestinal tract through TXI. We evaluated 72 and 60 images of 12 gastric neoplasms and 20 gastric atrophic/nonatrophic mucosa, respectively. The visibility of gastric mucosal atrophy and gastric neoplasm was assessed by six endoscopists using a previously reported visibility scale (1 = poor to 4 = excellent). Color differences between gastric mucosal atrophy and nonatrophic mucosa and between gastric neoplasm and adjacent areas were assessed using the International Commission on Illumination L*a*b* color space system. The visibility of mucosal atrophy and gastric neoplasm was significantly improved in TXI mode 1 compared with that in white-light imaging (WLI) (visibility score: 3.8 ± 0.5 vs. 2.8 ± 0.9, p p p

Barrett's esophagus (BE) is a precursor of esophageal adenocarcinoma (EAC). Therefore, an accurate diagnosis of BE is important for the subsequent follow-up and early detection of EAC. However, the definitions of BE have not been standardized worldwide; columnar-lined epithelium (CLE) without intestinal metaplasia (IM) and/or 1 cm is not diagnosed as BE in most countries. This study aimed to clarify the malignant potential of CLE without IM and/or 1 cm genetically.A total of 96 consecutive patients (including nine patients with EAC) who had CLE were examined. Biopsies for CLE were conducted, and patients were divided into those with IM and 1 cm (Group A) and those without IM and/or 1 cm (Group B). Malignant potential was assessed using immunochemical staining for p53. Moreover, causative genes were examined using next-generation sequencing (NGS) on ten patients without Helicobacter pylori infection and without atrophic gastritis.Of the 96 patients, 66 were in Group B. The proportion of carcinoma/dysplasia in Group A was significantly higher than that in Group B (26.7% in Group A and 1.5% in Group B; p 0.01). However, one EAC patient was found in Group B. In the immunostaining study for non-EAC patients, an abnormal expression of p53 was not observed in Group A, whereas p53 loss was observed in three patients (4.6%) in Group B. In the NGS study, a TP53 mutation was found in Group B.CLE without IM and/or 1 cm has malignant potential. This result suggests that patients with CLE as well as BE need follow-up.