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Early gastric cancers (EGCs) of the elevated type or with submucosal invasion are easily found by routine endoscopy. However, most early cancers are challenging to detect because of subtle morphological or color differences from surrounding atrophic mucosa and intestinal metaplasia. Linked color imaging (LCI) enhances mucosal color difference, making it easier to detect EGCs. The aim of this study is to clarify the advantages and possible disadvantages of LCI for screening for obscure EGC.A total of 665 malignant gastric lesions resected using endoscopic submucosal dissection between January 2015 and April 2018 were retrospectively reviewed. Obviously detectable lesions were not included in the main analysis when determining the target lesion. White light imaging (WLI)/LCI images of 508 endoscopically obscure malignant lesions were included in the final analysis and evaluated by three non-expert and three expert endoscopists using visibility scores for detection and extent.The detection visibility scores using LCI were significantly higher than those using WLI regardless of lesion characteristics including location, size, histological type, depth of invasion, and Helicobacter pylori status. The detection score improved in 46.4% cases and deteriorated in 4.9% when the modality changed from WLI to LCI. A mixed-effects multivariate logistic regression analysis showed that use of LCI (odds ratio [OR] 2.57), elevated type (OR 1.92), invasion to submucosa (OR 2.18) were significantly associated with improved visibility of EGC.Linked color imaging significantly improves visibility of EGC regardless of differences in lesion morphology, histology, location, depth of invasion, and H. pylori status compared to conventional WLI.

Video Video 1 Anatomical feature of duodenum for successfull duodenal ESD

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 tim...

Video Video 1 Demonstration of gastric endoscopic submucosal dissection using the pocket-creation method at the angle along the lesser curvature and fornix.

Sessile serrated adenomas/polyps (SSA/Ps), recently called sessile serrated lesions, have a neoplastic pathway in the large intestine and are treated as lesions with malignant potential. There are a few reports of traditional serrated adenomas in the duodenum but no reports of duodenal SSA/Ps. A 66-year-old man underwent screening upper gastrointestinal endoscopy and was found to have a white elevated lesion in the second portion of the duodenum. Magnifying blue laser imaging showed various sized villous-like structures with dilated crypt openings in the white surface mucosa, similar to a SSA/P. Based on these images, a duodenal adenoma was suspected at the time of endoscopic resection. Pathological findings of the resected specimen showed a saw-tooth structure corresponding to basal crypt dilatation and branching with mucus and positive immunostaining for MUC6 and MUC2, similar to a colonic SSA/P. MUC5AC did not stain the glandular crypt cells. KRAS mutation was detected. Immunohistochemical expression of Annexin A10 was clearly identified in the lesion. Although not all of molecular biological features were satisfied, these findings were similar to a colonic SSA/P which has malignant potential. This is the first report of a duodenal SSA/P which should be considered when evaluating elevated duodenal lesions.

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.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).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 (A continued increase in gastrin levels was not found during long-term vonoprazan therapy. Severe gastric atrophy is a significant risk factor for hypergastrinemia.

Sedation in gastroenterological endoscopy has become an important medical option in routine clinical care. Here, the Japan Gastroenterological Endoscopy Society and the Japanese Society of Anesthesiologists together provide the revised "Guidelines for sedation in gastroenterological endoscopy" as a second edition to address on-site clinical questions and issues raised for safe examination and treatment using sedated endoscopy. Twenty clinical questions were determined and the strength of recommendation and evidence quality (strength) were expressed according to the "MINDS Manual for Guideline Development 2017." We were able to release up-to-date statements related to clinical questions and current issues relevant to sedation in gastroenterological endoscopy (henceforth, "endoscopy"). There are few reports from Japan in this field (e.g., meta-analyses), and many aspects have been based only on a specialist consensus. In the current scenario, benzodiazepine drugs primarily used for sedation during gastroenterological endoscopy are not approved by national health insurance in Japan, and investigations regarding expense-related disadvantages have not been conducted. Furthermore, including the perspective of beneficiaries (i.e., patients and citizens) during the creation of clinical guidelines should be considered. These guidelines are standardized based on up-to-date evidence quality (strength) and supports on-site clinical decision-making by patients and medical staff. Therefore, these guidelines need to be flexible with regard to the wishes, age, complications, and social conditions of the patient, as well as the conditions of the facility and discretion of the physician.

Background and study aims Resecting large colorectal sessile tumors using endoscopic submucosal dissection (ESD) is challenging because of severe submucosal fibrosis. Previously, we reported that ESD strategy using the pocket-creation method (PCM) is useful for large colorectal sessile tumors, but there are no large studies reporting the effectiveness and safety of the PCM for resection of large colorectal sessile tumors. Patients and methods This was a retrospective review of 90 large colorectal sessile tumors in 89 patients who underwent ESD in our institution. Large colorectal sessile tumors were defined as polypoid lesions 20 mm or more in diameter. We divided them into PCM (n = 40) and conventional method (CM) groups (n = 50). The primary outcome measure was en bloc resection. The inverse-probability-treatment weighting (IPTW) approach was used to adjust for selection bias. Results Both PCM and CM achieved high en bloc resection (100 % vs. 94 %, non-adjusted P = 0.25, IPTW-adjusted P = 0.19) and R0 resection rates (88 % vs. 78 %, non-adjusted P = 0.28, IPTW-adjusted P = 0.27). When PCM was used, the rate of pathologically negative vertical margins was significantly greater than with the CM (IPTW-adjusted P = 0.045). The dissection time was significantly shorter (IPTW-adjusted P = 0.025) and dissection speed faster (IPTW-adjusted P = 0.013) using the PCM than when the CM was used. There was no significant difference in the incidence of adverse events (intraprocedural perforation and delayed bleeding, IPTW-adjusted P = 0.68). Conclusion Although en bloc resection and R0 resection rates were similar, PCM significantly increased the rate of negative vertical margins with rapid dissection for treatment of large colorectal sessile tumors.

Highlights • Gastric extremely well-differentiated adenocarcinoma (EWDA) is a rare type of gastric adenocarcinoma. • It is very difficult to preoperatively diagnose gastric EWDA presenting as an elevated lesion appearing like a submucosal tumor. • This is the first report of a gastric EWDA appearing like a submucosal tumor diagnosed by preoperative endoscopic submucosal dissection., Introduction Gastric adenocarcinomas with low grade atypia may be difficult to diagnose as gastric cancer by preoperative biopsy. We report an extremely well-differentiated adenocarcinoma (EWDA) of the stomach which appeared like a submucosal tumor diagnosed by preoperative endoscopic submucosal dissection. Presentation of case A 70-year-old male was referred with a 3-month history of a submucosal-appearing lesion in the gastric wall found on endoscopy. Biopsies of the lesion were performed and were inconclusive for neoplasia. Endoscopic ultrasonography showed a low echoic tumor growing into the fourth layer of the gastric wall. It was difficult to identify the tumor by repeat biopsy. Endoscopic submucosal dissection of the lesion was performed and revealed adenocarcinoma, and laparoscopic total gastrectomy was performed. Histopathologic evaluation showed that the tumor was stage IIA (T3N0M0). There is no recurrence 12 months after resection. Discussion Gastric EWDAs are rare lesions, accounting for 0.6% of all gastric cancers. It is difficult to diagnose gastric EWDA especially if it appears like a submucosal tumor. This lesion was finally diagnosed by endoscopic submucosal dissection. Conclusion Endoscopic submucosal dissection may facilitate establishing the preoperative diagnosis of a tumor thought to be a gastric EWDA based on its endoscopic appearance and pathological findings.

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 (P0.001). 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.

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 aims Early gastric cancer (EGC) lesions are often subtle and endoscopically poorly visible. The aim of this study is to evaluate the additive effect of linked color imaging (LCI) next to white-light endoscopy (WLE) for identification of EGC, when assessed by expert and non-expert endoscopists. Methods Forty EGC cases were visualized in corresponding WLE and LCI images. Endoscopists evaluated the cases in 3 assessment phases: Phase 1: WLE images only; Phase 2: LCI images only; Phase 3: WLE and LCI images side-to-side. First, 3 expert endoscopists delineated all cases. A high level of agreement between the expert delineations corresponded with a high AND/OR ratio. Subsequently, 62 non-experts indicated their preferred biopsy location. Outcomes of the study are as follows: (1) difference in expert AND/OR ratio; (2) accuracy of biopsy placement by non-expert endoscopists; and (3) preference of imaging modality by non-expert endoscopists. Results Quantitative agreement between experts increased significantly when LCI was available (0.58 vs. 0.46, p = 0.007). This increase was more apparent for the more challenging cases (0.21 vs. 0.47, p p p Conclusion The addition of LCI next to WLE improves visualization of EGC. Experts reach higher consensus on discrimination between neoplasia and inflammation when using LCI. Non-experts improve their targeted biopsy placement with the use of LCI. LCI therefore appears to be a useful tool for identification of EGC. Graphical abstract

Background/Aims: The long-term outcomes of patients after cessation of acotiamide therapy in patients with functional dyspepsia remains unclear. The aim of this study is to investigate the timing and predictors of recurrence of dyspepsia symptoms after cessation of acotiamide therapy for functional dyspepsia. Methods: Seventy patients treated with acotiamide for functional dyspepsia who then ceased treatment were enrolled. Changes in dyspepsia symptoms were evaluated using the Izumo scale, a self-reporting questionnaire of abdominal symptom-related quality of life. Patients were subclassified into epigastric pain, postprandial distress, and overlapped types. Results: The mean follow-up after cessation of acotiamide was 1.9 years. After cessation of acotiamide, 39 patients (56%) had recurrence. Kaplan-Meier analysis revealed a recurrence-free rate of 51% at 1 year. Predictors of recurrence evaluated with a Cox proportional hazards model showed that overlapped-type dyspepsia and consultation with the treating physician before cessation were identified as significant positive and negative predictors, respectively (p < 0.05). The resumption of acotiamide significantly decreased the score for dyspepsia symptoms at 1 month. Conclusions: Dyspepsia symptoms recur about one year after cessation of acotiamide therapy. Patients with overlapped-type dyspepsia should be carefully followed after cessation. Patients should consult their treating physician before stopping acotiamide.

Conventional endoscopy often misses early gastric cancers with minimal red discoloration because they cannot be distinguished from inflamed mucosa. We treated a patient with a small early gastric cancer that was difficult to diagnose using conventional endoscopy. Conventional endoscopy using a small-caliber endoscope showed only subtle red discoloration of the gastric mucosa. However, blue laser imaging showed a clearly discolored area measuring 10 mm in diameter around the red lesion, which was distinct from the surrounding inflamed mucosa. Irregular vessels on the tumor surface (suspicious for early gastric cancer) were observed even with small-caliber endoscopy. Biopsy revealed a well-moderately differentiated tubular adenocarcinoma, and endoscopic submucosal dissection was performed. Histopathological examination of the specimen confirmed well-moderately differentiated adenocarcinoma localized to the mucosa with slight depression compared to the surrounding mucosa, consistent with the endoscopic findings. This small early gastric cancer became clearly visible with blue laser imaging using small-caliber endoscopy.

Early detection and resection of neoplastic lesions are key objectives to diminish colorectal cancer mortality. Resection of superficial colorectal neoplasms, cold snare polypectomy, endoscopic mucosal resection, and endoscopic submucosal dissection have all been developed and used worldwide. The pocket-creation method facilitates the resection of tumors in difficult and routine locations. Early detection is the most important first step to maximize the benefits of recent advancements in endoscopic techniques. However, the detection of small, flat-shaped, or faded color lesions remains difficult. Linked color imaging, a novel multi-light technology, facilitates the recognition of minor differences in tissue by enhancing the color contrast between early colorectal neoplasms and surrounding normal mucosa in a bright field of view. The most striking feature of linked color imaging is its ability to display the color of early neoplastic lesions as distinct from inflammatory changes, both of which have similar “redness” when viewed using white light imaging. To increase the detection rate of neoplasms, linked color imaging should be used from the outset for endoscopic observation. Early detection of superficial colorectal tumors can result in decreased mortality from colorectal cancer and maintain a good quality of life for patients.

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 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.

Background: Duodenal ulcers are classified into bulbar and post-bulbar ulcers. The aim of this study is to compare the long-term outcomes of patients with post-bulbar ulcer bleeding and those with bulbar ulcer bleeding. Methods: A total of 272 patients with hemorrhagic duodenal ulcers requiring hospitalization were included. Their medical records were retrospectively reviewed. Results: All patients were categorized as bulbar or post-bulbar bleeding ulcer groups. The post-bulbar ulcer group had more patients of advanced age, concurrent malignancy, diabetes mellitus, hypertension, cirrhosis, and chronic kidney disease undergoing hemodialysis. We performed long-term follow-up for an average of 2.6 years. The mortality rate during the follow-up period in the post-bulbar ulcer group was significantly higher than that in the bulbar ulcer group (p < 0.001). The PNED score was a better predictor of 30-day mortality compared to the complete Rockall score and the Glasgow-Blatchford Score. Predictors of mortality were evaluated using a Cox proportional hazards regression model. In multivariate analysis, post-bulbar ulcer, concurrent malignancy, cirrhosis, antiplatelet/anticoagulant use, and transfusion were significant predictors of mortality. Conclusions: Patients with post-bulbar ulcers have a poorer prognosis than those with bulbar ulcers. After the diagnosis of hemorrhagic post-bulbar duodenal ulcer, close follow-up is necessary.

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.