林 芳和

Gastric mucosal changes associated with long-term potassium-competitive acid blocker and proton pump inhibitor (PPI) therapy may raise concern. In contrast to that for PPIs, the evidence concerning the safety of long-term potassium-competitive acid blocker use is scant. Vonoprazan (VPZ) is a representative potassium-competitive acid blocker released in Japan in 2015. In order to shed some comparative light regarding the outcomes of gastric mucosal lesions associated with a long-term acid blockade, we have reviewed six representative gastric mucosal lesions: fundic gland polyps, gastric hyperplastic polyps, multiple white and flat elevated lesions, cobblestone-like gastric mucosal changes, gastric black spots, and stardust gastric mucosal changes. For these mucosal lesions, we have evaluated the association with the type of acid blockade, patient gender, Helicobacter pylori infection status, the degree of gastric atrophy, and serum gastrin levels. There is no concrete evidence to support a significant relationship between VPZ/PPI use and the development of neuroendocrine tumors. Current data also shows that the risk of gastric mucosal changes is similar for long-term VPZ and PPI use. Serum hypergastrinemia is not correlated with the development of some gastric mucosal lesions. Therefore, serum gastrin level is unhelpful for risk estimation and for decision-making relating to the cessation of these drugs in routine clinical practice. Given the confounding potential neoplastic risk relating to H. pylori infection, this should be eradicated before VPZ/PPI therapy is commenced. The evidence to date does not support the cessation of clinically appropriate VPZ/PPI therapy solely because of the presence of these associated gastric mucosal lesions.

Background and study aims Diagnostic performance of a computer-aided diagnosis (CAD) system for deep submucosally invasive (T1b) colorectal cancer was excellent, but the "regions of interest" (ROI) within images are not obvious. Class activation mapping (CAM) enables identification of the ROI that CAD utilizes for diagnosis. The purpose of this study was a quantitative investigation of the difference between CAD and endoscopists. Patients and methods Endoscopic images collected for validation of a previous study were used, including histologically proven T1b colorectal cancers (n = 82; morphology: flat 36, polypoid 46; median maximum diameter 20 mm, interquartile range 15-25 mm; histological subtype: papillary 5, well 51, moderate 24, poor 2; location: proximal colon 26, distal colon 27, rectum 29). Application of CAM was limited to one white light endoscopic image (per lesion) to demonstrate findings of T1b cancers. The CAM images were generated from the weights of the previously fine-tuned ResNet50. Two expert endoscopists depicted the ROI in identical images. Concordance of the ROI was rated by intersection over union (IoU) analysis. Results Pixel counts of ROIs were significantly lower using 165K[x103] [108K-227K] than by endoscopists (300K [208K-440K]; P < 0.0001) and median [interquartile] of the IoU was 0.198 [0.024-0.349]. IoU was significantly higher in correctly identified lesions (n = 54, 0.213 [0.116-0.364]) than incorrect ones (n=28, 0.070 [0.000-0.2750, P = 0.033). Concusions IoU was larger in correctly diagnosed T1b colorectal cancers. Optimal annotation of the ROI may be the key to improving diagnostic sensitivity of CAD for T1b colorectal cancers.

BACKGROUND: Gastroesophageal reflux disease (GERD) symptoms frequently recur after cessation of acid blockers. The presence of a hiatal hernia may worsen GERD symptoms and increase the risk of esophageal malignancy. The aim of this study is to clarify the timing and predictors for recurrence of GERD symptoms after cessation of vonoprazan (VPZ) therapy. METHODS: A retrospective observational study involved 86 patients who underwent cessation of VPZ therapy for symptomatic GERD. Collated data from medical record review included the endoscopic findings and Izumo scale score. RESULTS: The mean duration of continuous VPZ therapy before cessation was 7.9 months. GERD symptoms requiring the resumption of VPZ therapy recurred in 66 of 86 patients (77%). Kaplan-Meier analysis showed that overall recurrence-free rates at 6 months, one and two years after VPZ cessation were 44%, 32% and 23%, respectively. Alcohol use, the presence of a hiatal hernia and long-term therapy for more than six months were identified as significant positive predictors for symptomatic recurrence. Notably, hiatal hernia had the highest hazard ratio in both univariate and multivariate analyses. The recurrence-free rate in patients with a hiatal hernia was much lower at 6 months than in patients without a hiatal hernia (15% and 51%, respectively p = 0.002). After the symptomatic recurrence, GERD symptoms improved significantly after one-month VPZ therapy. CONCLUSION: The rate of symptomatic recurrence after VPZ cessation in patients with GERD is considerable. Cessation of acid suppression therapy should be cautious in patients with both a hiatal hernia and GERD.

Background The pocket-creation method (PCM) has been developed to overcome technical difficulties associated with endoscopic submucosal dissection (ESD), nevertheless, opening of the pocket could still be technically challenging. We developed a novel technique named the PCM with single clip traction (PCM-CT), which utilizes a general-purpose reopenable clip as a traction device to maintain stability during the procedure. To date, no prospective study has compared the efficacy between PCM-CT and the PCM. The aim of this study is to investigate the effectiveness of PCM-CT compared to the PCM in a randomized controlled trial. Methods This randomized controlled clinical trial was conducted at four Japanese institutions. Patients with superficial colorectal neoplastic lesions were included following Japanese guidelines for colorectal cancer. Seven moderately experienced endoscopists performed the ESD procedures using either PCM-CT or PCM. Results A total of 100 patients were enrolled in this study. PCM-CT procedure achieved significant faster dissection speed and reduced the procedure time and pocket-opening time compared to the PCM (27.0±14.5 vs 21.4±10.8 mm2/min, 95% confidence interval (CI) [0.5, 10.7], p=0.031, 64.8±47.6 vs 81.8±57.9 min, 95% CI [-38.2, 4.3], p=0.116, 30.0±28.9 vs 37.8±33.0 min, 95% CI [-20.2, 4.6], p=0.217). En-bloc resection and R0 resection rates were not significantly different between the two groups (100% vs 100%, p=1.000, 100% vs 96%, p=0.495). No significant differences were observed in adverse events between the two groups. Conclusion ESD facilitated by the novel PCM-CT appears to be significantly faster. Additionally, both PCM-CT and PCM achieved high R0 resection rate.

BACKGROUND AND AIMS: Acid suppression improves dyspepsia symptoms but the efficacy of vonoprazan for functional dyspepsia remains unclear. The aim of this study is to evaluate the effectiveness of vonoprazan therapy for functional dyspepsia without heartburn. METHODS: Patients receiving vonoprazan 10 mg once daily or acotiamide 100 mg three times daily for more than one month were included and retrospectively reviewed. Functional dyspepsia was diagnosed based on the ROME IV criteria. Patients with heartburn were excluded. Eighty-five patients were divided into vonoprazan (n=48) and acotiamide (n=37) groups. RESULTS: There were no significant differences at baseline between the vonoprazan and acotiamide groups. The functional dyspepsia score significantly improved in both groups (p<0.001). The degree of score reduction (55% vs 59%, p=0.559) and the resolution rates (21% vs 30%, p=0.345) were similar. Epigastric pain and postprandial distress scores were significantly improved in both groups, and the degree of improvement of each score was similar. Constipation and diarrhea scores were significantly improved in both groups, and the degree of improvement similar. CONCLUSION: These preliminary results suggest that vonoprazan is effective for the treatment of functional dyspepsia without heartburn in the short-term, with results similar to acotiamide therapy.

BACKGROUND AND AIMS: Differentiation of colorectal cancers with deep submucosal invasion (T1b) from colorectal cancers with superficial invasion (T1a) or no invasion (Tis) is not straightforward. This study aimed to develop a computer aided diagnosis system (CADx) to establish the diagnosis of early-stage cancers using non-magnified endoscopic white light images alone. METHODS: A total of 1513 lesions (Tis 1074, T1a 145, T1b 294) in 5108 images were collected from 1470 patients at ten academic hospitals and assigned to training and testing datasets (3:1). The ResNet-50 network was used as the backbone to extract features from images. Over sampling and focal loss were used to compensate class imbalance of invasive stage. Diagnostic performance was assessed using the testing dataset including 403 CRCs with 1392 images. Two experts and two trainees read the identical testing dataset. RESULTS: At 90% cutoff for per lesion score, CADx showed the highest specificity of 94.4% [95% confidence interval: 91.3 - 96.6], with 59.8% [48.3 - 70.4] sensitivity and 87.3% [83.7 - 90.4] accuracy. The area under the characteristic curve was 85.1% [79.9 - 90.4] for CADx, 88.2% [83.7 - 92.8] for expert 1, 85.9% [80.9 - 90.9] for expert 2, 77.0% [71.5 - 82.4] for trainee 1 (vs. CADx: p=0.0076), and 66.2% [60.6 - 71.9] for trainee 2 (p<0.0001). The function was also confirmed on nine short videos. CONCLUSION: CADx developed with endoscopic white light images showed excellent per lesion specificity and accuracy for T1b lesion diagnosis, equivalent to experts and superior to trainees. (UMIN000037053) (249 =<250 words).

Background and study aims  Underwater endoscopic mucosal resection (UEMR) does not always result in en bloc resection of large colorectal lesions. The aim of this study was to demonstrate the feasibility of en bloc resection with progressive polyp contraction with underwater endoscopic mucosal resection (PP-CUE) of large, superficial colorectal lesions. The advantage of PP-CUE is to enable resection of a superficial non-polypoid lesion that is larger than the snare diameter. Patients and methods  Eleven consecutive lesions in ten patients who underwent UEMR with PP-CUE of large superficial colorectal lesions (20 mm or greater) were included. Results  The median lesion diameter was 24 mm (interquartile range [IQR], 20-24 mm). All lesions were larger than the 15-mm rotatable snare that was used. Median procedure time and PP-CUE time were 11 minutes (IQR, 8.5-12.3) and 2.3 minutes (IQR, 1.9-3.4), respectively. Pathological diagnoses of resected specimens included six adenomas, three sessile serrated lesions, and two slightly invasive submucosal carcinomas. En bloc and R0 resection rates were both 91 % (10/11). No adverse events occurred. Conclusions  PP-CUE is useful to resect superficial non-polypoid colorectal lesions 20 to 25 mm in diameter in an en bloc fashion.

PURPOSE: Computer-aided diagnosis systems for polyp characterization are commercially available but cannot recognize subtypes of sessile lesions. This study aimed to develop a computer-aided diagnosis system to characterize polyps using non-magnified white-light endoscopic images. METHODS: A total of 2249 non-magnified white-light images from 1030 lesions including 534 tubular adenomas, 225 sessile serrated adenoma/polyps, and 271 hyperplastic polyps in the proximal colon were consecutively extracted from an image library and divided into training and testing datasets (4:1), based on the date of colonoscopy. Using ResNet-50 networks, we developed a classifier (1) to differentiate adenomas from serrated lesions, and another classifier (2) to differentiate sessile serrated adenoma/polyps from hyperplastic polyps. Diagnostic performance was assessed using the testing dataset. The computer-aided diagnosis system generated a probability score for each image, and a probability score for each lesion was calculated as the weighted mean with a log10-transformation. Two experts (E1, E2) read the identical testing dataset with a probability score. RESULTS: The area under the curve of classifier (1) for adenomas was equivalent to E1 and superior to E2 (classifier 86%, E1 86%, E2 69%; classifier vs. E2, p < 0.001). In contrast, the area under the curve of classifier (2) for sessile serrated adenoma/polyps was inferior to both experts (classifier 55%, E1 68%, E2 79%; classifier vs. E2, p < 0.001). CONCLUSION: The classifier (1) developed using white-light images alone compares favorably with experts in differentiating adenomas from serrated lesions. However, the classifier (2) to identify sessile serrated adenoma/polyps is inferior to experts.

BACKGROUND: Long-term acid suppression during vonoprazan therapy causes hypergastrinemia which may induce gastric mucosal changes such as fundic gland and hyperplastic polyps. The aim of this study is to clarify the long-term changes in serum gastrin levels and risk factors for hypergastrinemia. METHODS: From July 2016 to April 2020, 48 patients receiving vonoprazan 10 mg once daily for more than one year were reviewed. Serum gastrin level was evaluated by radioimmunoassay in a fasting condition (reference range 37-172 pg/ml). RESULTS: The baseline median gastrin level was 100 (range, 54-415) pg/ml. The gastrin level over 4 years was 700-1200 pg/ml, which plateaued at 1.5 years. Multivariate analysis revealed factors associated with gastrin levels 12 months after starting vonoprazan and identified severe gastric atrophy as a significant positive risk factor (p = .046). The gastrin level over 4 years in patients with severe gastric atrophy and no atrophy was approximately 900-1500 and 500-1000 pg/ml, respectively. Female gender was also identified as a positive factor, although it was not statistically significant (p = .087). The gastrin level over 4 years in females was approximately 900-1300 pg/ml, greater than in males (500-900 pg/ml). CONCLUSION: A continued increase in gastrin levels was not found during long-term vonoprazan therapy. Severe gastric atrophy is a significant risk factor for hypergastrinemia.

OBJECTIVES: In light emitting diode (LED) and LASER colonoscopy, linked color imaging (LCI) superiority to white light imaging (WLI) for polyp detection is shown separately. We analyzed the non-inferiority of LCI between LED and LASER colonoscopy and that of WLI. METHODS: We prospectively observed lesions with WLI and LCI using LED and LASER colonoscopy from January 2021 to August 2021. All images were evaluated randomly by 12 endoscopists (six non-experts and six experts in three institutions) using the polyp visibility score; 4 (excellent), 3 (good), 2 (fair) and 1 (poor). The comparison score (LED better/similar/LASER better) for redness and brightness was evaluated for WLI and LCI pictures of each lesion. RESULTS: Finally, 63 lesions were evaluated, and the mean polyp size was 24.5±13.4 mm. Histopathology revealed 13 serrated lesions and 50 adenomatous/cancerous lesions. The mean polyp visibility scores of LCI pictures were significantly higher than those of WLI in LED (3.35±0.85 vs. 3.08±0.91, p<0.001) and LASER (3.40±1.71 vs. 3.05±0.97, p<0.001) group, and the non-inferiority of LCI pictures between LED and LASER was significant (p<0.001). The comparison scores revealed that the evaluation of redness and brightness (LED better/similar/LASER better) were 26.8%/40.1%/33.1% and 43.5%/43.5%/13.0% for LCI pictures (p<0.001) and 20.6%/44.3%/35.1% and 60.3%/31.7%/8.0% for WLI pictures (p<0.001), respectively. CONCLUSIONS: The non-inferiority of polyp visibility with WLI and LCI in LED and LASER colonoscopy is shown. WLI and LCI of LED tended to be brighter and less reddish than those of LASER.

The safety of long-term proton pump inhibitor (PPI) and vonoprazan (VPZ) use is a relatively recent concern. Gastric mucosal redness was reported as a VPZ-associated lesion in a previous study. The aim of this study was to investigate the prevalence and risk factors for gastric mucosal redness. Between December 2020 and November 2021, 1,101 patients who underwent esophagogastroduodenoscopy were reviewed. The cohort was divided into four groups: Control (n=580), histamine-2 receptor antagonist (H2RA) (n=65), PPI (n=146) and VPZ groups (n=310). Gastric mucosal redness was present in 48/1,101 patients (4%). The prevalence in controls, H2RA, PPI and VPZ groups was 1.9% (11/580), 1.5% (1/65), 6.2% (9/146) and 8.7% (27/310), respectively. Both the PPI and VPZ groups had a significantly higher prevalence of gastric mucosal redness compared with the control group (P<0.001). In the multivariate analysis, PPI and VPZ use were significantly associated with gastric mucosal redness. Fundic gland polyps, gastric hyperplastic polyps, multiple white and flat elevated lesions, cobblestone-like mucosa, and stardust gastric mucosa were also significantly associated with PPI and VPZ use in the multivariate analysis. Back-to-back analysis showed that gastric mucosal redness was not seen before starting PPI/VPZ in most patients. The duration of treatment with VPZ was investigated to determine if it affected the prevalence of gastric mucosal redness. There were no significant differences in treatment duration among patients with and without gastric mucosal redness (mean ± standard deviation: 3.0±1.5 vs. 2.5±1.4 years, P=0.077). In conclusion, the prevalence of gastric mucosal redness was low but was associated with PPI and VPZ use.

<jats:sec><jats:title>Background and aims</jats:title><jats:p>The standard treatment for stage T1b colorectal cancers with 1,000µm or greater submucosal invasion is surgical resection. However, the risk of lymph node metastases is only 1-2% when excluding risk factors for metastases other than depth of submucosal invasion. The number of elderly patients with significant comorbidities is increasing with societal aging in Japan. Therefore, local endoscopic resection of T1b colorectal cancers needs more consideration in the future. We previously showed that the pocket-creation method (PCM) for endoscopic submucosal dissection (ESD) is useful regardless of the morphology, including large sessile tumors with submucosal fibrosis, or location of the colorectal tumor. However, some T1b colorectal cancers have pathologically positive margins even when using the PCM. We retrospectively investigated the causes of failure to achieve negative vertical margins.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We retrospectively analyzed 953 colorectal tumors in 886 patients resected with the PCM. Finally, 65 pathological T1b colorectal cancers after <jats:italic>en bloc</jats:italic> resection were included in this study. ESD specimens and recorded procedure videos of T1b cancer resections with pathologically positive vertical margins were reviewed.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The 65 cancers were divided into positive vertical margin (VM+ group) and negative vertical margin (VM- group) groups with 10 [10/65 (15%)] and 55 [55/65 (85%)] patients in each group, respectively. There was a significant difference in the rate of submucosal fibrosis (P=0.012) and dissection speed (P=0.044). There were no significant differences between the two groups in other regards. When verifying 8/10 available videos in the VM+ group, endoscopic technical factors led to positive vertical margins in five patients, and essential pathological factors of ESD led to positive vertical margins in the other three. Six of these eight patients underwent additional surgical resection. No residual tumor was identified in six T1b cancers. None of these six resected specimens contained lymph node metastases on pathological examination.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>The PCM resulted in a high rate of negative-vertical-margin resections. The PCM resulted in complete resection of T1b cancers when examining additional surgical specimens. ESD using the PCM is a viable option for the endoscopic treatment of T1b colorectal cancers.</jats:p></jats:sec>

BACKGROUND: This is the first report from a multicenter prospective cohort study of colorectal neuroendocrine tumor (NET), the C-NET STUDY, conducted to assess the long-term outcomes of the enrolled patients. This report aimed to elucidate the clinicopathological features of the enrolled patients and lesions. METHODS: Colorectal NET patients aged 20-74 years were consecutively enrolled and followed up at 50 institutions. The baseline characteristics and clinicopathological findings at enrollment and treatment were assessed. RESULTS: A total of 495 patients with 500 colorectal NETs were included. The median patient age was 54 years, and 85.3% were asymptomatic. The most frequent lesion location was the lower rectum (88.0%); 99.4% of the lesions were clinically diagnosed to be devoid of metastatic findings, and 95.4% were treated with endoscopic resection. Lesions < 10 mm comprised 87.0% of the total, 96.6% had not invaded the muscularis propria, and 92.6% were classified as WHO NET grade 1. Positive lymphovascular involvement was found in 29.2% of the lesions. Its prevalence was high even in small NETs with immunohistochemical/special staining for pathological assessment (26.4% and 40.9% in lesions sized < 5 mm and 5-9 mm, respectively). Among 70 patients who underwent radical surgery primarily or secondarily, 18 showed positive lymph node metastasis. CONCLUSIONS: The characteristics of real-world colorectal NET patients and lesions are elucidated. The high positivity of lymphovascular involvement in small NETs highlights the necessity of assessing the clinical significance of positive lymphovascular involvement based on long-term outcomes, which will be examined in later stages of the C-NET STUDY. TRIAL REGISTRATION NUMBER: UMIN000025215.

Background and study aims  Endoscopic submucosal dissection (ESD) is a standard method for minimally invasive resection of superficial gastrointestinal tumors. The pocket creation method (PCM) facilitates ESD regardless of location in the gastrointestinal tract. The aim of this systematic review and meta-analysis is to evaluate the effectiveness and safety of ESD for superficial neoplasms in the upper and lower gastrointestinal tract comparing the PCM to the non-PCM. Methods  Randomized controlled, prospective, and retrospective studies comparing the PCM with the non-PCM were included. Outcomes included en bloc resection, R0 resection, dissection speed, delayed bleeding and perforation. Pooled odds ratios (ORs) with 95 % confidence intervals (CIs) using the Mantel-Haenszel random effect model were documented. Results  Eight studies including gastric, duodenal, and colorectal ESD were included. The en bloc resection rate was significantly higher in the PCM group than the non-PCM group (OR 3.87, 95 %CI 1.24-12.10 P  = 0.020). The R0 resection rate was significantly higher in the PCM group than the non-PCM group (OR 2.46, 95 %CI 1.14-5.30, P  = 0.020). The dissection speed was significantly faster in the PCM group than the non-PCM group (mean difference 3.13, 95 % CI 1.35-4.91, P  < 0.001). The rate of delayed bleeding was similar in the two groups (OR 1.13, 95 %CI 0.60-2.15, P =  0.700). The rate of perforation was significantly lower in the PCM group than the non-PCM group (OR 0.34, 95 %CI 0.15-0.76, P =  0.009). Conclusions  The PCM facilitates high-quality, fast and safe colorectal ESD. Further studies are needed regarding the utility of PCM in ESD of the upper gastrointestinal tract.

Endoscopic submucosal dissection (ESD) is rapidly becoming the standard treatment for superficial gastrointestinal tumors because ESD can achieve complete local resection facilitating thorough pathological examination of the resected specimen. The pocket-creation method (PCM) has been established to perform safe and reliable ESD obtaining a high-quality pathological specimen. A minimal mucosal incision using PCM minimizes leakage of submucosally injected solution, which results in prolonged mucosal elevation. A limited-space submucosal pocket created using PCM makes the endoscope tip stable. A conical cap, small-caliber-tip transparent (ST) hood is used when performing PCM. The submucosa can be cut along the ideal dissection line just above the muscularis with minimal thermal damage because the tip of the ST hood produces both traction and countertraction to stretch the submucosal tissue in the pocket. PCM is recommended as the standard strategy not only for colorectal ESD but also for upper-gastrointestinal ESD. It is expected that the use of traction techniques will make PCM easier to perform.

Background and Study Aims: The resection strategy for rectal neuroendocrine tumors (NET) < 10 mm is not uniform. We compared the utility of underwater endoscopic mucosal resection (UEMR) to endoscopic submucosal resection with a ligation device (ESMR-L) to resect rectal NETs. Patients and Methods: Patients with rectal NET < 10 mm treated with UEMR or ESMR-L were included. Their medical records were retrospectively reviewed. Results: Thirty-two patients were divided into a UEMR group (n = 7) and an ESMR-L group (n = 25). Histopathological diagnosis of NET by biopsy was known before resection in 43% (3/7) in the UEMR group and 68% (17/25) in the ESMR-L group, (p = 0.379). UEMR was performed on an outpatient basis for all patients, and 92% of ESMR-L (23/25) were performed as inpatient procedures (p < 0.001). The procedure time was significantly shorter in the UEMR group than in the ESMR-L group [median (IQR), min, 6 (5-8) vs. 12 (9-14), p = 0.002]. En bloc resection and R0 resection rates were 100% in both groups. Pathological evaluations were predominantly NET G1 in both groups (UEMR: 7/7, 100% and ESMR-L: 23/25, 92%). Two patients in the ESMR-L group developed delayed bleeding, controlled by endoscopic hemostasis. Device costs were significantly higher in the ESMR-L group than the UEMR group by approximately US$180 [median (IQR), $90.45 (83.64-108.41) vs. $274.73 (265.86-292.45), P < 0.001]. Conclusion: UEMR results in similar resection quality with shorter procedure time and lower costs compared to ESMR-L. We recommend UEMR for the resection of rectal NET < 10 mm.

BACKGROUND: Helicobacter pylori (H. pylori) eradication success increases the incidence of erosive esophagitis by normalization of gastric acid secretion. The aim of this study is to clarify predictors and timing for the development of symptomatic gastroesophageal reflux disease (GERD) after successful H. pylori eradication based on long-term follow-up. METHODS: From April 2014 to October 2020, 330 patients with H. pylori infections treated with a standard triple-drug regimen were enrolled, and their records retrospectively reviewed. Development of symptomatic GERD was defined as requiring proton pump inhibitor or vonoprazan therapy to treat symptoms. RESULTS: The mean follow-up period was 2.8 years, and symptomatic GERD developed in 41 (12%) patients during the study period. Overall rates of GERD-symptom free patients at 6 months, 1, and 2 years after eradication were 97%, 93%, and 89%, respectively. We evaluated predictors for the development of symptomatic GERD using a Cox proportional hazards regression model. In multivariate analysis, being a current smoker, having functional dyspepsia, hiatal hernia, and severe gastric atrophy were identified as significant predictive factors. The GERD domain score in the Izumo scale was significantly decreased 1 month after vonoprazan therapy consistent with effective treatment of symptomatic GERD. CONCLUSIONS: The rate of development of symptomatic GERD after successful H. pylori eradication is low over long-term follow-up and is easily controlled by vonoprazan therapy. However, patients with smoking habits, functional dyspepsia, hiatal hernia, or severe gastric atrophy should be followed carefully after eradication.

Background and study aims  Endoscopic submucosal dissection (ESD) of superficial gastric lesions involving the pyloric ring is difficult. The pocket-creation method (PCM) with a small-caliber-tip transparent hood can overcome this difficulty by compressing the pyloric sphincter applying both traction and counter-traction. The aim of this study is to clarify the usefulness of the PCM for ESD of superficial gastric neoplasms involving the pyloric ring compared to the conventional method (CM). Patients and methods  From October 2006 to August 2019, 66 gastric lesions requiring duodenal submucosal dissection beyond the pyloric ring in 66 patients were resected. The CM was mainly performed in the first period (CM group, n = 46) and the PCM in the second period (PCM group, n = 20). We retrospectively reviewed their medical records. Results  Although no significant differences were observed in en bloc resection rates between the two groups, the PCM group had a significantly higher R0 resection rate than the CM group ( P  = 0.047). There were no holes in resected specimens in the PCM group while three specimens in the CM group had a hole. The dissection speed in the PCM group tended to be higher than in the CM group, although it did not reach statistical significance ( P  = 0.148). No significant differences were observed for the incidence of adverse events. Conclusions  This is the first study reporting the advantages of the PCM over the CM for ESD of gastric lesions involving the pyloric ring. We believe that the PCM is an effective strategy to compress the pyloric sphincter and facilitates R0 resection.

Background and study aims  The pocket-creation method (PCM) facilitates dissection of the central part of a tumor. We previously developed the PCM with clip traction (PCM-CT) to facilitate opening the mucosal pocket, which otherwise could become cumbersome. In the present study, we aimed to examine the feasibility of PCM-CT for colorectal endoscopic submucosal dissection (ESD). Patients and methods  PCM-CT was performed on 30 patients with early colorectal tumors from October 2019 to April 2020. PCM-CT allows efficient opening of the mucosal pocket by using the PCM to dissect the center of the lesion and then apply traction with a single clip after making a circumferential mucosal incision. Results  The median specimen major axis length, ESD time, ESD speed, and en bloc resection rate were 48 mm, 84 minutes, 20 mm 2 /min, and 100 % (30/30), respectively. The success rates for the traction clip and median single-clip-traction time were 100 % (30/30) and 1.5 minutes, respectively. Conclusions  Colorectal ESD using PCM-CT is a simple and promising method.

Superficial colonic neoplasms sometimes extend into a diverticulum. Conventional endoscopic mucosal resection of these lesions is considered challenging because colonic diverticula do not have a muscularis propria and are deeply inverted. Even if the solution is carefully injected below the mucosa at the bottom of the diverticulum, the mucosa is rarely elevated from the diverticular orifice, and it is usually just narrowed. Although endoscopic submucosal dissection or full-thickness resection with an over-the-scope clip device enables the complete resection of these lesions, it is still challenging, time consuming and expensive. Underwater endoscopic mucosal resection without submucosal injection (UEMR) is an innovative technique enabling en bloc resection of superficial colon lesions. We report three patients with colon adenomas extending into a diverticulum treated with successful UEMR. UEMR enabled rapid and safe en bloc resection of colon lesions extending into a diverticulum.

Vonoprazan, a novel potassium-competitive acid blocker, results in greater inhibition of gastric acid secretion than proton pump inhibitors (PPI). The aim of this study was to assess the long-term outcomes of patients with PPI-resistant gastroesophageal reflux disease (GERD) treated with vonoprazan. The medical records of patients with symptomatic GERD treated with vonoprazan for 1 year were retrospectively reviewed. Changes in abdominal symptoms were assessed using the Izumo scale, a self-reported questionnaire which is useful in evaluating the symptoms of GERD, epigastric pain, postprandial distress, constipation and diarrhea, and is commonly used in routine clinical practice. A total of 30 patients were included and stratified into a non-erosive (n=22) and erosive group (n=8). At baseline, postprandial distress symptoms were significantly greater in the non-erosive group compared with the erosive group (P=0.013). Even with vonoprazan therapy, symptoms of GERD in the non-erosive group were refractory compared with the erosive group, and required additional treatment in a larger proportion of patients (45 vs. 13%). GERD symptoms in the non-erosive group significantly improved from baseline and remained better after 1 year of vonoprazan therapy, similar to the erosive group. In addition, vonoprazan improved epigastric pain and postprandial distress symptoms in the non-erosive group, and 1 year of vonoprazan therapy did not aggravate constipation or diarrhea. In conclusion, 1 year of vonoprazan therapy improves GERD symptoms in patients with PPI-resistant GERD.

Background and Aims: We previously showed that the performance of artificial intelligence (AI) in diagnosing deep (≥1mm) submucosally invasive (T1b) colorectal cancer was relatively good after training with non-magnified white light images (sensitivity 80%, specificity 87%). However, the "region of interest" (ROI) within the image that was responsible for the AI diagnosis is a black box. Recently, the class activation mapping (CAM) technique has been developed, enabling identification of the ROI within the image that AI utilized for making the diagnosis. In this study, we aimed to investigate features of the ROI selected by AI using CAM and clarify the similarities and differences between AI and endoscopists. Methods: We selected endoscopic digital images that were used for training or validation of our AI system in our previous study, comprising histologically proven T1b colorectal cancers (n= 114, 0-Is 69, 0-IIa 39, 0-IIc 6; maximum diameter 16.5±13.4mm). The application of CAM was limited to a maximum of two images per lesion from which T1b cancer was diagnosed. The CAM images were generated on ResNet50, and the ROI defined by AI was depicted in red. Two expert colonoscopists rated characteristics of the ROI following discussion. The outcome measures were concordance of the ROI defined by AI with the ROI defined by expert endoscopists, and endoscopic features analyzed by AI, including color (red or non-red), surface morphology (depressed, flat, protruding), presence of bleeding, and fold convergence. Concordance of the ROI defined by AI and the ROI that was defined by expert endoscopists was rated by concordance area and classified into excellent (≥75%), fair (≥25% <75%) and poor (<25%). Results: CAM images were successfully generated for all 226 images. The level of concordance between the ROI defined by AI and the ROI that was defined by expert endoscopists was excellent in 39%, fair in 34% and poor in 27%. In images showing poor concordance, the ROI defined by AI was distant from the T1b cancer. After excluding lesions with poor concordance, the vast majority (91%) of the ROI defined by AI was concordant with the ROI containing endoscopists' identification of red color, and a small proportion (21%) of the ROI defined by AI revealed bleeding. Among the lesions detected by AI, the surface morphology was depressed in 39% , flat in 5% and protruding in 57%. Fold convergence was observed in 34% of the ROI defined by AI. Conclusions: Most of the ROIs identified by AI were concordant with ROIs defined by experienced endoscopists, although AI may diagnose T1b colorectal cancer using different features of the ROI. Since a quarter of ROIs were present within normal mucosa, annotation of the image that the image should be reviewed by expert endoscopists may improve the diagnostic accuracy of AI for T1b colorectal cancer.

Background and study aims  Colorectal cancers (CRC) with deep submucosal invasion (T1b) could be metastatic lesions. However, endoscopic images of T1b CRC resemble those of mucosal CRCs (Tis) or with superficial invasion (T1a). The aim of this study was to develop an automatic computer-aided diagnosis (CAD) system to identify T1b CRC based on plain endoscopic images. Patients and methods  In two hospitals, 1839 non-magnified plain endoscopic images from 313 CRCs (Tis 134, T1a 46, T1b 56, beyond T1b 37) with sessile morphology were extracted for training. A CAD system was trained with the data augmented by rotation, saturation, resizing and exposure adjustment. Diagnostic performance was assessed using another dataset including 44 CRCs (Tis 23, T1b 21) from a third hospital. CAD generated a probability level for T1b diagnosis for each image, and > 95 % of probability level was defined as T1b. Lesions with at least one image with a probability level > 0.95 were regarded as T1b. Primary outcome is specificity. Six physicians separately read the same testing dataset. Results  Specificity was 87 % (95 % confidence interval: 66-97) for CAD, 100 % (85-100) for Expert 1, 96 % (78-100) for Expert 2, 61 % (39-80) for both gastroenterology trainees, 48 % (27-69) for Novice 1 and 22 % (7-44) for Novice 2. Significant differences were observed between CAD and both novices ( P  = 0.013, P  = 0.0003). Other diagnostic values of CAD were slightly lower than of the two experts. Conclusions  Specificity of CAD was superior to novices and possibly to gastroenterology trainees but slightly inferior to experts.