大澤 博之

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/AIMS: Underwater endoscopic mucosal resection (UEMR) is the standard resection method for superficial non-ampullary duodenal tumors (SNADETs). We developed a novel UEMR technique that creates an anchor by protruding the distal fold with a saline injection (UEMR-A). The aim of this study was to clarify the usefulness of UEMR-A compared to conventional UEMR (UEMR-C). METHODS: This retrospective observational study included patients who underwent UEMR for SNADETs. RESULTS: A total of 141 patients were included and divided into UEMR-A (n=54) and UEMR-C (n=87) groups. Lesion resection was performed significantly more frequently by an expert endoscopist in the UEMR-C group compared to the UEMR-A group (p<0.001). The procedure time for UEMR-A was significantly shorter than that for UEMR-C (p=0.018), despite the additional time required for submucosal injection. The R0 resection rate was significantly higher in the UEMR-A group than in the UEMR-C group (p=0.004). The horizontal margins were significantly clearer in the UEMR-A group than in the UEMR-C group (p=0.018). Multivariate analysis revealed that the use of UEMR-A was the only significant positive factor for R0 resection. CONCLUSIONS: The UEMR-A technique for SNADETs appears to improve R0 resection rates and reduce procedure times compared to the UEMR-C technique.

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 main therapeutic modality of early upper gastrointestinal neoplasms has shifted from surgery to endoscopic therapy. The role of endoscopy has also expanded not only for more accurate diagnosis of neoplasms but also for the determination of extent and depth of neoplasms with a combination of multiple electronically modified images acquired with image-enhanced endoscopy (IEE) for assessing the feasibility of endoscopic treatment. SUMMARY: These IEE with or without magnifying endoscopy including narrow-band imaging, blue laser imaging, and linked color imaging (LCI) using narrow-band light have greatly changed the diagnosis for upper gastrointestinal neoplasms. These modalities produce high color contrast between cancer and surrounding mucosa at distant views and clear visualization of surface and vessels at close-up observations. LCI shows purple color of intestinal metaplasia (IM) distinct from other inflammatory gastric mucosae and facilitates the recognition of early gastric cancers often surrounded by IM. Recently, ultrathin endoscopy has provided high-resolution images similar to standard-caliber endoscopy. In addition, these advanced IEEs that integrate computer-assisted artificial intelligence systems are marked and will improve our diagnostic performance for neoplasia in the future. KEY MESSAGE: New IEE with sufficient brightness and color contrast has increasingly been used based on accumulated evidence for early and accurate detection of neoplastic lesions. We provide recent articles relevant to endoscopic diagnosis with IEE on esophageal, gastric, and duodenal neoplasms. Endoscopic equipment that integrates artificial intelligence support system is now being introduced into routine clinical use and is expected to enhance early detection of neoplastic lesions.

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.

The pink color sign in iodine unstained areas is useful to differentiate esophageal squamous cell carcinoma (ESCC) from other lesions. However, some ESCCs have obscure color findings which affect the ability of endoscopists to differentiate these lesions and determine the resection line. Using white light imaging (WLI), linked color imaging (LCI) and blue laser imaging (BLI), 40 early ESCCs were retrospectively evaluated using images before and after iodine staining. Visibility scores for ESCC by expert and non-expert endoscopists were compared using these three modalities and color differences measured for malignant lesions and surrounding mucosa. BLI had the highest score and color difference without iodine staining. Each determination with iodine was much higher than without iodine regardless of the modality. With iodine, ESCC mainly appeared pink, purple and green using WLI, LCI and BLI, respectively and visibility scores determined by non-experts and experts were significantly higher for LCI (both p < 0.001) and BLI (p = 0.018 and p < 0.001) than for WLI. The score with LCI was significantly higher than with BLI among non-experts (p = 0.035). With iodine, the color difference using LCI was twice that with WLI and one with BLI was significantly larger than with WLI (p < 0.001). These greater tendencies were found regardless of location, depth of cancer or intensity of pink color using WLI. In conclusion, areas of ESCC unstained by iodine were easily recognized using LCI and BLI. Visibility of these lesions is excellent even by non-expert endoscopists, suggesting that this method is useful to diagnose ESCC and determine the resection line.

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.

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.

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 < 0.001). Non-experts placed the biopsy mark more accurately with LCI (82.3% vs. 87.2%, p < 0.001). Again this increase was more profound for the more challenging cases (70.4% vs. 83.4%, p < 0.001). Non-experts indicated to prefer LCI over WLE. 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.

Background and study aims  Ultrathin endoscopy causes a minimal gag reflex and has minimal effects on cardiopulmonary function. Linked color imaging (LCI) is useful for detection of malignancies in the digestive tract. The aim of this study was to clarify whether LCI with ultrathin endoscopy facilitates detection of early gastric cancer (EGC) despite its lower resolution compared with high-resolution white light imaging (WLI) with standard endoscopy. Patients and methods  This was a retrospective analysis with prospectively collected video, including consecutive 166 cases of EGC or gastric atrophy alone. Ninety seconds of screening video was collected using standard and ultrathin endoscopes with both WLI and LCI for each case. Three expert endoscopists assessed each video and the sensitivity of detecting EGC calculated. Color difference calculations were performed. Results  Sensitivities using ultrathin WLI, ultrathin LCI, standard WLI, and standard LCI for the identification of cancer were 66.0 %, 80.3 %, 69.9 %, and 84.0 %, respectively. The color difference between malignant lesions and surrounding mucosa with ultrathin LCI and standard LCI were significantly higher than using ultrathin WLI or standard WLI, supported subjectively by the visibility score. Ultrathin LCI color difference and visibility score were significantly higher than standard WLI. Conclusions  LCI with a low-resolution ultrathin endoscope is superior to WLI with a high-resolution standard endoscope for gastric cancer screening. This suggests that the high color contrast between EGC and the surrounding mucosa is more important than high-resolution images.

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: 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.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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: A novel potassium-competitive acid blocker, vonoprazan (VPZ), improves first-line Helicobacter pylori eradication success. The aim of this systematic review is to clarify the effectiveness and safety of second-line H. pylori eradication therapy comparing VPZ and proton pump inhibitor (PPI)-based regimens. METHODS: Medline (PubMed), EMBASE, Web of Science, Cochrane Library, and the Japan Medical Abstract Society Database were searched. RESULTS: We selected 16 studies for quantitative review. Forest plot analysis showed significant superiority of VPZ over PPI-based regimens in overall second-line H. pylori eradication success (OR 1.51, 95% CI 1.27-1.81, p < 0.001). Forest plots from 2 studies with propensity score matched analysis showed significant superiority of VPZ over PPI-based regimens (OR 3.09, 95% CI 1.71-5.58, p < 0.001). The remaining 14 studies with per-protocol analysis and the full analysis set also showed significant superiority (OR 1.40, 95% CI 1.16-1.69, p < 0.001). Regarding adverse events, Forest plot analysis did not show a significant difference between the 2 regimens (OR 0.88, 95% CI 0.58-1.32, p = 0.53). CONCLUSIONS: A VPZ-based regimen has significant superiority over a PPI-based regimen for second-line H. pylori eradication therapy. A VPZ-based second-line H. pylori eradication regimen can be the first choice.

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.

A 62-year-old man with a flat early esophageal cancer was referred for endoscopic treatment. White light imaging revealed a pale red lesion, whereas linked color imaging (LCI) and blue laser imaging (BLI) yielded purple and brown images, respectively. Iodine staining demonstrated a large unstained area with a homogenous but very weak pink-color sign. This area appeared more clearly as purple and green on LCI and BLI, respectively; however, a different colored portion was observed at the 4 o'clock position inside the iodineunstained area. Histopathology findings of the resected specimen revealed squamous intraepithelial neoplasia at the 4 o'clock position and an esophageal squamous cell carcinoma in the remaining iodine-unstained area. LCI and BLI combined with iodine staining produce characteristic images that overcomes the pink-color sign, reflecting the histological features of a flat esophageal neoplasm. This new method is useful for detailed evaluation of early flat squamous cell neoplasms.

BACKGROUND: Linked color imaging (LCI) increases the visibility of early gastric cancers, which may be associated with characteristic findings including background purple mucosae. These lesions are found in areas of chronic gastritis and surrounding mucosa. The aim of this study is to objectively characterize these lesions by color differences and color component values using LCI. METHODS: Fifty-two patients with early gastric cancer were enrolled. Color differences were calculated prospectively in malignant lesions and adjacent mucosa and compared with histological findings in resected specimens. Color component values of L*, a*, and b* were compared between purple and non-purple mucosae in areas of chronic gastritis. Based on histological findings, the accuracy of identifying gastric intestinal metaplasia was calculated. RESULTS: Cancers and surrounding mucosa in 74% of lesions had similar colors using white light imaging (WLI), whereas purple mucosa surrounded part or all of cancers appearing orange-red, orange or orange-white using LCI. Greater color differences were seen using LCI compared to WLI, including flat-type cancers, leading to higher contrast. The surrounding purple mucosa corresponded histologically to intestinal metaplasia, facilitating the identification of malignant lesions. Forty lesions (83%) with purple mucosa and eight lesions (17%) with non-purple mucosa in areas of chronic gastritis were diagnosed as intestinal metaplasia by biopsy (83% accuracy). Color component values of purple mucosa differ significantly from those of non-purple mucosae. CONCLUSIONS: LCI images have higher color contrast between early gastric cancers and surrounding mucosa compared to WLI. A characteristic purple color around gastric cancers using LCI represents intestinal metaplasia.

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.

In routine upper and lower gastrointestinal endoscopy, overlooking neoplastic lesions is inevitable even for well-trained endoscopists. Various methods have been reported to improve the detection of gastrointestinal neoplasms including chromoendoscopy, special endoscopes, and processor and image enhanced technologies. Equipment-based image enhanced endoscopy (e-IEE) using narrow band imaging (NBI) and blue laser imaging (BLI) is useful to characterize known lesions with magnification at a close-up view. However, they are not useful for the early detection of superficial, pale neoplasms, or both because of the weak image at a distant view in a wide lumen such as the stomach or colon. Linked color imaging (LCI) is a novel pre- and post-processing technology developed by Fujifilm Corporation that has sufficient brightness to illuminate a wide lumen. LCI delineates early gastric cancers as orange-red and intestinal metaplasia as purple. LCI improves the adenoma detection rate in the colon and decreases the polyp miss rate. LCI contributes to the detection of superficial lesions throughout the gastrointestinal tract by enhancing the color contrast between the neoplasm and the surrounding mucosa. LCI can distinguish them by their specific color allocation based mainly on the distribution of capillaries. The authors believe that moving forward, LCI should be used in routine upper and lower gastrointestinal endoscopy.

OBJECTIVE: The novel potassium-competitive acid blocker, vonoprazan, provides rapid and effective acid suppression. The aim of this study is to evaluate the long-term outcomes of patients with symptomatic gastroesophageal reflux disease (GERD) treated with vonoprazan. METHODS: This retrospective cohort study included 55 patients with symptomatic GERD treated with vonoprazan who have been followed for more than one year. The effectiveness of vonoprazan on gastrointestinal symptoms was evaluated using the Izumo scale, a self-reported questionnaire reflecting quality of life related to various abdominal symptoms. RESULTS: These 55 patients with symptomatic GERD had non-erosive reflux disease (n = 30) or erosive esophagitis (n = 25). Vonoprazan (10 mg) for one month improved GERD symptoms in 89% (responders) and the improvement was maintained at one year in 82% without additional treatment. One-year maintenance therapy resulted in sustained resolution of GERD symptoms in 47%. Of the 49 responders, nine patients had relapse of GERD symptoms and dose escalation of vonoprazan improved the symptoms in six patients. Postprandial distress and the presence of erosive esophagitis before starting vonoprazan were identified as significant negative and positive predictors of sustained resolution of GERD symptoms for one year, respectively. Epigastric pain, postprandial distress, constipation and diarrhea were significantly improved at one-month and maintained at one year. After one-year of treatment, the endoscopic healing rate of erosive esophagitis was 95%. CONCLUSION: One-year treatment with vonoprazan significantly improves GERD symptoms and endoscopic healing of erosive esophagitis is satisfactory. The long-term use of vonoprazan is effective and useful to control GERD.

Vonoprazan-based regimens have improved the rate of successful Helicobacter pylori (H. pylori) eradication, but it has not reached 100%. The aim of this study is to clarify significant predictors of successful H. pylori eradication using a vonoprazan-based regimen. In this retrospective cohort study, 174 patients who underwent primary H. pylori eradication therapy were included. All patients underwent esophagogastroduodenoscopy before treatment. The vonoprazan-based regimen includes amoxicillin 750 mg, clarithromycin 200 mg and vonoprazan 20 mg twice daily for one week. Pre-treatment with a proton pump inhibitor (PPI) was defined as continued PPI use for more than four weeks prior to eradication therapy. The rates of successful eradication were 83% (145/174) in intention-to-treat analysis and 85% (145/171) in per-protocol analysis. Predictors of successful eradication among 171 patients were evaluated in per-protocol analysis. In univariate analysis, male gender was a significant positive predictor of successful eradication (odds ratio [OR] 3.813, 95% confidence interval [CI] 1.363-10.663, p = 0.010) and pre-treatment with PPIs was a negative predictor (OR 0.193, 95%CI 0.076-0.485, p < 0.001). In multivariate analysis, male gender remained a positive predictor (OR 3.826, 95%CI 1.317-11.116, p = 0.013), and pre-treatment with PPIs (OR 0.232, 95%CI 0.087-0.615, p = 0.003) remained a negative predictor. In conclusion, pre-treatment with PPIs before eradication therapy decreases the rate of successful eradication. Therefore, it may be desirable to discontinue pre-treatment with PPIs prior to eradication therapy, because of the potential to improve the rate of successful eradication.

BACKGROUND/AIMS: A submucosal cushion of sodium hyaluronate facilitates gastric and colorectal endoscopic submucosal dissection (ESD). However, few studies have evaluated the utility of sodium hyaluronate for ESD of esophageal lesions. The aim of this study is to evaluate the utility and safety of sodium hyaluronate for ESD of superficial esophageal squamous cell neoplasms (ESCN). MATERIAL AND METHODS: We retrospectively reviewed 111 ESCN in 86 patients treated by ESD between September 2007 and April 2013. There were four double cancers, with 107 ESD procedures analyzed. RESULTS: The en bloc resection rate was 99% (106/107). The R0 resection rate was 93% (99/107). Of 106 specimens resected en bloc, four specimens had a positive horizontal margin, two specimens had non-assessable horizontal margins and one specimen had non-assessable horizontal and vertical margins. One patient with a non-assessable horizontal margin developed local recurrence seven months later, treated by repeat ESD. Delayed bleeding occurred in two procedures (2%), and intra-procedural perforation occurred in four (4%). None required operative repair. Endoscopy trainees performed 33 of 107 (31%) ESD procedures. Post-ESD stenosis requiring dilation occurred following five procedures (5%). CONCLUSIONS: Sodium hyaluronate for ESD of ESCN achieves a high R0 resection rate with a low rate of adverse events.

BACKGROUND AND AIMS: Long-term outcomes in patients with functional dyspepsia remain elusive. Acotiamide, a prokinetic drug, has been available in Japan since 2013. The aim of this study was to assess long-term outcomes in patients with functional dyspepsia treated with acotiamide. METHODS: We retrospectively reviewed 79 consecutive patients with functional dyspepsia whose symptoms improved with acotiamide therapy and who were followed for more than one year. All patients underwent esophagogastroduodenoscopy prior to acotiamide therapy. The mean follow-up was 1.9 (range, 1.0-3.3) years. We assessed the patients' symptom severity using the Izumo scale, which reflects changes in various abdominal symptoms. RESULTS: At one year, dyspepsia symptoms recurred in 25% (20/79) of the patients. In multivariate analysis, severe dyspepsia was significantly associated with increased recurrence (odds ratio [OR] 15.04, 95% confidence interval [CI] 1.73-130.47, p=0.013). Continued use of acotiamide for one year diminished the recurrence of dyspepsia symptoms significantly (OR 0.16, 95%CI 0.04-0.61, p=0.006). The influence of these significant predictors on long-term outcomes was analyzed using the Kaplan-Meier method. Patients with severe dyspepsia before starting acotiamide had significantly more recurrences than those with mild symptoms (p=0.004, log-rank test). Patients who continued acotiamide therapy throughout the follow-up period had significantly fewer recurrences than those who stopped therapy (p<0.001). CONCLUSIONS: Over the long-term, patients with functional dyspepsia have a considerable rate of recurrence of dyspepsia. Severe dyspepsia before treatment increases the recurrence rates, while adherence to an acotiamide therapeutic regimen decreases recurrence rate.

Gastroesophageal reflux disease (GERD) is commonly treated by primary care physicians. Although proton pump inhibitors (PPI) have been the mainstay of GERD treatment for two decades, in some patients GERD is refractory to standard dose PPI for more than eight weeks and is referred to as PPI-resistant GERD. Vonoprazan, a novel competitive acid blocker, became available in Japan for the treatment of patients with GERD, and has greater acid inhibition than existing PPIs. The aim of the present study was to determine the effect of vonoprazan 10 mg daily on PPI-resistant GERD. We retrospectively reviewed 24 patients with PPI-resistant GERD treated with vonoprazan 10 mg daily. The Izumo scale was used to evaluate the effect of vonoprazan before and one month after treatment, which reflects quality of life related to gastrointestinal symptoms. The overall rates of improvement and resolution of GERD symptoms were 88% (21/24) and 42% (10/24), respectively, and the score was significantly decreased (before 5.8±1.7, at one month 1.9±1.9, P<0.001). To evaluate the influence of esophageal erosions despite prior PPI treatment, the patients were divided into erosive (n=6) and non-erosive groups (n=18). Vonoprazan achieved 100% (6/6) improvement in the erosive group and 83% (15/18) in the non-erosive group. Patients in the erosive group had a significantly higher rate of resolution than in the non-erosive group [83% (5/6) vs 28% (5/18), P=0.017]. No adverse events occurred. Other GI symptoms in patients with PPI-resistant GERD were evaluated. The scores for epigastric pain, postprandial distress, constipation and diarrhea were unchanged during the treatment period. In conclusion, vonoprazan 10 mg daily is effective for the treatment of patients with PPI-resistant GERD. Vonoprazan resolves GERD symptoms in patients with erosions more than in those without erosions. This is the first report on the effect of vonoprazan 10 mg on PPI-resistant GERD.

The effect of acotiamide on gastrointestinal symptoms is undefined. The aim of this study is to evaluate the effect of acotiamide on abdominal symptoms in patients with functional dyspepsia. We retrospectively reviewed 51 patients treated with acotiamide. We evaluated patient quality of life using the Izumo scale that detects changes in quality of life caused by abdominal symptoms. Acotiamide ameliorated the symptoms of functional dyspepsia at one and three months (improved: 61% vs 80%, p=0.029 and resolved: 17% vs 33%, p=0.069). We then evaluated the effect of acotiamide on epigastric pain syndrome (EPS) (n=33) and postprandial distress syndrome (PDS) (n=41). Acotiamide treatment showed an early effect on rates of improvement (63%) and resolution (42%) of EPS symptoms at one month, maintained up to three months (69% and 39%, respectively). Both rates of improvement and resolution of PDS symptoms showed a significant increase from one month to three months (56% vs 78%, p=0.021 and 17% vs 46%, p=0.004, respectively). The severity of functional dyspepsia symptoms before treatment was significantly associated with failed resolution of functional dyspepsia symptoms (p=0.013). Acotiamide improves and resolves EPS symptoms as well as PDS symptoms. PDS symptoms take longer to resolve than EPS symptoms. J. Med. Invest. 63: 230-235, August, 2016.