Differences in Mucosal Permeability Among Patients With Ulcerative Colitis Classified Based on the Colonic Location and Disease Activity.

INTRODUCTION: Factors affecting mucosal permeability (MP) in ulcerative colitis (UC) are largely unknown. We aimed to investigate the difference in MP among patients with UC classified according to the colonic locations and to evaluate the correlations between local MP and endoscopic or histological activity of UC. METHODS: The transepithelial electrical resistance (TER), which is inversely proportional to permeability, of tissue samples from the mucosa of the ascending colon, descending colon, and rectum of patients with UC and healthy individuals (HIs) was measured by using the Ussing chamber. TERs were compared between patients with UC and HIs and evaluated according to colonic locations and disease activity of UC. RESULTS: Thirty-eight patients with UC and 12 HIs were included in this study. Both in HIs and patients with UC, MP tends to be higher in the anal side. TER in the ascending colon was significantly lower in patients with UC than in HIs (45.3 ± 9.0 Ω × cm 2 vs 53.5 ± 9.7 Ω × cm 2 , P = 0.01). The increased permeability in UC was observed also in the descending colon, only when the inflammation involved the location. A significant correlation between TER and endoscopic activity was found in the rectum only ( r = -0.49, P = 0.002). There were no significant correlations between TERs and UC histology. DISCUSSION: The MP in the colon differs according to the colonic location. The ascending colon among patients with UC showed disease-specific changes in MP, whereas the MP is increased in proportion to the endoscopic activity in the rectum.

Investigation of risk factors for metachronous recurrence in patients with early gastric adenocarcinoma by miRNA-mRNA integral profiling.

The mechanism of metachronous recurrence (MR) after performing endoscopic treatment for early gastric adenocarcinoma (GAC) and eradicating Helicobacter pylori (H. pylori) is unknown. To elucidate the mechanism and risk factors of MR, we analyzed gene expression at multiple locations of the gastric mucosa. We selected each five patients with MR and without MR (control), after early GAC treatment and eradication of H. pylori. Mucosal tissue was collected from four sites in the stomach of each patient as biopsy specimens for mRNA sequencing, gene set enrichment analysis, and microRNA (miRNA) sequencing. We also performed correlation analysis and target prediction on pathways. As a result, endoscopically, the MR group had more intestinal metaplasia and enlarged folds. A total of 384 mRNAs presented changes in expression and 31 gene sets were enriched in the MR group. Immune-related pathways were enriched in the entire stomach, and the IFN-α response had the highest enrichment score. Additionally, 32 miRNAs revealed changes in their expression. Correlation analysis and target prediction with genes in the gene set of IFN-α response revealed that 10 miRNA-mRNA pairs presented a significant correlation. Immune-related pathways with miRNAs in the gastric mucosa after H. pylori eradication may be a risk factor for MR.

Treatment strategy changes for inflammatory bowel diseases in biologic era: results from a multicenter cohort in Japan, Far East 1000.

Many molecular targeted agents, including biologics, have emerged for inflammatory bowel diseases (IBD), but their high prices have prevented their widespread use. This study aimed to reveal the changes in patient characteristics and the therapeutic strategies of IBD before and after the implementation of biologics in Japan, where the unique health insurance system allows patients with IBD and physicians to select drugs with minimum patient expenses. The analysis was performed using a prospective cohort, including IBD expert and nonexpert hospitals in Japan. In this study, patients were classified into two groups according to the year of diagnosis based on infliximab implementation as the prebiologic and biologic era groups. The characteristics of therapeutic strategies in both groups were evaluated using association analysis. This study analyzed 542 ulcerative colitis (UC) and 186 Crohn's disease (CD). The biologic era included 53.3% of patients with UC and 76.2% with CD, respectively. The age of UC (33.9 years vs. 38.8 years, P < 0.001) or CD diagnosis (24.3 years vs. 31.9 years, P < 0.001) was significantly higher in the biologic era group. The association analysis of patients with multiple drug usage histories revealed that patients in the prebiologic era group selected anti-tumor necrosis factor (TNF)-α agents, whereas those in the biologic era group preferred biologic agents with different mechanisms other than anti-TNF-α. In conclusion, this study demonstrated that both patient characteristics and treatment preferences in IBD have changed before and after biologic implementation.

Clinical Features Focusing on Extraintestinal Manifestations in Japanese Patients with Inflammatory Bowel Diseases: Far East 1000.

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.

Long-term course of gastric submucosal tumors: growth speed and size-increasing factors.

BACKGROUND AND AIMS: Gastric submucosal tumors (SMTs) are treated or monitored according to GI stromal tumor guidelines, but the adequacy of the guidelines has not been thoroughly examined. We investigated the long-term course of gastric SMTs to determine the validity of guideline-based follow-up methods and the factors contributing to their size increase. METHODS: This study included gastric SMTs diagnosed as GI mesenchymal tumors (GIMTs) by using EUS and followed up with EUS. The percentage and speed of GIMT enlargement and factors associated with the enlargement were investigated by using the Cox proportional hazards model. RESULTS: From January 1994 to May 2022, a total of 925 gastric SMTs were evaluated with EGD, and 231 SMTs were diagnosed as GIMTs. Of the 231 GIMTs, 145 were examined by EUS more than twice and were followed up for >6 months. The mean ± standard deviation follow-up period was 5.20 ± 4.04 years (range, 0.5-17.3 years), with 39 (26.9%) of 145 GIMTs increasing in size with a mean doubling time of 3.60 ± 3.37 years. A multivariate analysis of factors influencing tumor growth revealed that irregular extraluminal borders were an increasing factor (hazard ratio, 3.65; 95% confidence interval, 1.26-10.52), initial tumor size ≤9.5 mm (hazard ratio, .23; 95% confidence interval, 0.07-0.77) was a nonincreasing factor, and GIMTs with calcification (n = 13) did not increase in size. CONCLUSIONS: Tumor growth in gastric GIMTs <9.5 mm in diameter and/or with calcification is rare. Follow-up intervals for these lesions could be extended.

Magnified endoscopy with texture and color enhanced imaging with indigo carmine for superficial nonampullary duodenal tumor: a pilot study.

This pilot study aimed to investigate the utility of texture and color enhancement imaging (TXI) with magnified endoscopy (ME) for the preoperative diagnosis of superficial nonampullary duodenal epithelial tumors (SNADETs). We prospectively evaluated 12 SNADETs. The visibility for ME-TXI, ME with indigo carmine (ICME)-white-light imaging (WLI), ICME-TXI compared to ME-NBI (narrow-band imaging) was scored (+ 2 to - 2 ME-NBI was set as score 0) by 3 experts. Scores + 2 and + 1 were defined as improved visibility. The intra-observer and interobserver agreement for improved visibility of surface structure (SS) was evaluated. Sensitivity, specificity, and positive predictive value (PPV) for Vienna Classification (VCL) C4/5 associated with the preoperative diagnosis of ICME-TXI were analyzed. The SS visibility score of ICME-TXI was significantly higher than that of ME-NBI, ME-TXI, and ICME-WLI (P < 0.001 respectively). The kappa coefficients of reliability for intra-observer and interobserver agreement for the SS visibility improvement with ICME-TXI were 0.96, 1.00, 1.00 and 0.70, 0.96, 0.96 respectively. All endoscopists preferred ICME-TXI for visualizing SS mostly for all lesions. The sensitivity, specificity, and PPV (%) of ICME-TXI for VCL C4/5 were 80, 66.7, and 63.2, respectively. ICME-TXI facilitates the visibility of the SS of SNADETs and may contribute to their preoperative diagnosis.

Anti-TNFα antibody versus non-anti-TNFα molecular agents for ulcerative colitis patients who failed initial anti-TNFα therapy.

BACKGROUND AND AIM: 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. METHODS: 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. RESULTS: 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). CONCLUSION: Non-ATA may be suitable in UC patients as the subsequent biologics regardless of the outcome of the first ATA.

Long-term outcomes of cold snare polypectomy for superficial non-ampullary duodenal epithelial tumors.

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.

Development and evaluation of a double-check support system using artificial intelligence in endoscopic screening for gastric cancer.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: The DCSS showed excellent capability in detecting lesions and pointing out low-quality images.

Clinical Characteristics of Esophageal Motility Disorders in Patients With Heartburn.

BACKGROUND/AIMS: Esophageal motility disorders (EMDs) contribute to the pathophysiology of gastroesophageal reflux disease. However, the causes of EMDs and their impact on gastroesophageal reflux disease-associated symptoms remain unknown. This study aims to elucidate clinical features associated with various types of EMDs in patients with heartburn symptoms. METHODS: Of the 511 patients who underwent high-resolution manometry, 394 who were evaluated for heartburn symptoms were examined. Patients subjected to high-resolution manometry were classified into 4 groups: outflow obstruction group, hypermotility group, hypomotility group, and normal motility group. Symptoms were evaluated using 3 questionnaires. Patient characteristics and symptoms for each EMD type were compared with those of the normal motility group. RESULTS: Of the 394 patients, 193 (48.9%) were diagnosed with EMDs, including 71 with outflow obstruction, 15 with hypermotility, and 107 with hypomotility. The mean dysphagia score was significantly higher in each of the 3 EMD groups compared with those with normal motility. The mean acid reflux and dyspepsia scores were significantly lower in the outflow obstruction group (P < 0.05). The mean body mass index and median Brinkman index were significantly higher in the hypermotility group (P = 0.001 and P = 0.018, respectively), whereas the mean diarrhea and constipation scores were significantly lower in the hypomotility group (P < 0.05). CONCLUSIONS: The results of our study indicate that different EMDs have distinct characteristics. Cigarette smoking and high body mass index were associated with esophageal hypermotility. Assessment of the dysphagia symptom scores may help identify patients with EMDs.

Genetic profiles of Barrett's esophagus and esophageal adenocarcinoma in Japanese patients.

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 < 0.01]. The genetic variants of 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).

Efficacy of Texture and Color Enhancement Imaging in visualizing gastric mucosal atrophy and gastric neoplasms.

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 < 0.01 for mucosal atrophy; visibility score: 2.8 ± 1.0 vs. 2.0 ± 0.9, p < 0.01 for gastric neoplasm). Regarding gastric atrophic and nonatrophic mucosae, TXI mode 1 had a significantly greater color difference than WLI (color differences: 14.2 ± 8.0 vs. 8.7 ± 4.2, respectively, p < 0.01). TXI may be a useful observation modality in the endoscopic screening of the upper gastrointestinal tract.

The Efficacy of Linked Color Imaging in the Endoscopic Diagnosis of Barrett's Esophagus and Esophageal Adenocarcinoma.

BACKGROUND: The present study aimed to evaluate the efficacy of linked color imaging (LCI) in diagnosing Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). METHODS: A total of 112 and 12 consecutive patients with BE and EAC were analyzed. The visibility scores of BE and EAC ranging from 4 (excellent visibility) to 0 (not detectable) were evaluated by three trainees and three experts using white light imaging (WLI), LCI mode, and blue laser imaging bright (BLI-b) mode. In addition, L∗a∗b∗ color values and color differences (ΔE∗) were evaluated using the CIELAB color space system. RESULTS: The visibility score of the BE in LCI mode (2.94 ± 1.32) was significantly higher than those in WLI (2.46 ± 1.48) and BLI-b mode (2.35 ± 1.46) (p < 0.01). The color difference (ΔE∗) from the adjacent gastric mucosa in LCI mode (17.11 ± 8.53) was significantly higher than those in other modes (12.52 ± 9.37 in WLI and 11.96 ± 6.59 in BLI-b mode, p < 0.01). The visibility scores of EAC in LCI mode (2.56 ± 1.47) and BLI-b mode (2.51 ± 1.28) were significantly higher than that in WLI (1.64 ± 1.46) (p < 0.01). The color difference (ΔE∗) from the adjacent normal Barrett's mucosa in LCI mode (19.96 ± 7.97) was significantly higher than that in WLI (12.95 ± 11.86) (p = 0.03). CONCLUSION: The present findings suggest that LCI increases the visibility of BE and EAC and contributes to the improvement of the detection of these lesions.