The presence of hiatal hernia is a significant predictor for symptomatic recurrence after cessation of vonoprazan therapy for gastroesophageal reflux disease: a long-term observational study.

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.

Recent Progress of Image-Enhanced Endoscopy for Upper Gastrointestinal Neoplasia and Associated Lesions.

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.

Performance of an artificial intelligence-based diagnostic support tool for early gastric cancers: Retrospective study.

OBJECTIVES: Endoscopists' abilities to diagnose early gastric cancers (EGCs) vary, especially between specialists and nonspecialists. We developed an artificial intelligence (AI)-based diagnostic support tool "Tango" to differentiate EGCs and compared its performance with that of endoscopists. METHODS: The diagnostic performances of Tango and endoscopists (34 specialists, 42 nonspecialists) were compared using still images of 150 neoplastic and 165 non-neoplastic lesions. Neoplastic lesions included EGCs and adenomas. The primary outcome was to show the noninferiority of Tango (based on sensitivity) over specialists. The secondary outcomes were the noninferiority of Tango (based on accuracy) over specialists and the superiority of Tango (based on sensitivity and accuracy) over nonspecialists. The lower limit of the 95% confidence interval (CI) of the difference between Tango and the specialists for sensitivity was calculated, with >-10% defined as noninferiority and >0% defined as superiority in the primary outcome. The comparable differences between Tango and the endoscopists for each performance were calculated, with >10% defined as superiority and >0% defined as noninferiority in the secondary outcomes. RESULTS: Tango achieved superiority over the specialists based on sensitivity (84.7% vs. 65.8%, difference 18.9%, 95% CI 12.3-25.3%) and demonstrated noninferiority based on accuracy (70.8% vs. 67.4%). Tango achieved superiority over the nonspecialists based on sensitivity (84.7% vs. 51.0%) and accuracy (70.8% vs. 58.4%). CONCLUSIONS: The AI-based diagnostic support tool for EGCs demonstrated a robust performance and may be useful to reduce misdiagnosis.

Predictors and timing for the development of symptomatic gastroesophageal reflux disease after successful Helicobactor pylori eradication therapy.

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.

Long-term changes in serum gastrin levels during standard dose vonoprazan therapy.

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.

Long-Term Outcomes in Patients with Post-Bulbar Ulcer Bleeding Compared to Bulbar Ulcer Bleeding in the Duodenum.

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.

Linked color imaging improves identification of early gastric cancer lesions by expert and non-expert endoscopists.

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.

Usefulness of linked color imaging for the detection of obscure early gastric cancer: Multivariate analysis of 508 lesions.

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.

Effectiveness and Safety of Vonoprazan versus Proton Pump Inhibitors for Second-Line Helicobacter pylori Eradication Therapy: Systematic Review and Meta-Analysis.

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.

Timing and Predictors of Recurrence of Dyspepsia Symptoms after Cessation of Acotiamide Therapy for Functional Dyspepsia: A Long-Term Observational Study.

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.

Pulmonary melanocytic nevus - A case report with a mutation analysis of common driver oncogenes.

Nevi are benign melanocytic tumors, and some nevi are considered to develop into malignant melanomas. Most nevi arise in the skin, but nevi occasionally occur in the conjunctiva, esophageal mucosa, or at other sites. Pulmonary melanocytic nevi are extremely rare, and only one case has been reported in the literature. Here, we present a case of pulmonary melanocytic nevus, involving a BRAF gene mutation (V600E), and we discuss the potential significance of this condition as a precursor to pulmonary malignant melanoma.

Long-term outcomes of patients with symptomatic gastroesophageal reflux disease treated with vonoprazan.

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.

Esophageal endoscopic submucosal dissection using sodium hyaluronate is safe and effective.

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.

Clinical management of Helicobacter pylori--the Japanese perspective.

BACKGROUND: After the approval of health insurance coverage of eradication therapy for Helicobacter pylori-positive peptic ulcer disease (PUD) in 2000, comprehensive coverage for H. pylori infection itself was implemented in 2013. METHODS: We did a literature search using PubMed database on the management of H. pylori infection including indications, regimens, outcomes of current eradication therapies, trends of antibiotic resistance rates and proposed third-line rescue therapy in Japan. We also collected data on changes of eradication rates in our hospital by searching electronic medical records. RESULTS: After implementation of insurance coverage of eradication therapy for PUD, dramatic reduction of the number patients with PUD as well as spending on ulcer drug was documented. According to the current regulation, proton pump inhibitor (PPI)-based triple therapy with 2 antibiotics, amoxicillin (AMPC) plus clarithromycin, for 7 days is approved as the first-line therapy. After failure of the first-line therapy, PPI plus AMPC and metronidazole is authorized as the second line, which maintains an excellent eradication rate of over 90% in Japan. When these two therapies fail, a sitafloxacin-based therapy seems to be most promising among many rescue regimens. CONCLUSION: Comprehensive public health insurance coverage of H. pylori infection will promote eradication in Japanese people infected with H. pylori, whose risk of developing gastric cancer has been shown to be high. It also provides us a unique opportunity to study whether the broader indications can accelerate the reduction of gastric cancer in Japan in the same way we witnessed the reduction of PUD.

Present and future status of flexible spectral imaging color enhancement and blue laser imaging technology.

The usefulness of flexible spectral imaging color enhancement (FICE) has been reported for evaluating the esophagus, stomach, and small and large intestine. Higher contrast is shown between cancer and the surrounding mucosa in the esophagus and stomach and may facilitate the detection of gastric cancers missed by white light imaging alone. The surface patterns of gastric mucosa are clearly visualized in non-malignant areas but are irregular and blurred in malignant areas, leading to clear demarcation. Capsule endoscopy with FICE detects angiodysplasia and erosions of the small intestine. The surface and vascular pattern with FICE is useful for the differential diagnosis of colorectal polyps. However, FICE remains somewhat poor at visualizing mucosal microvasculature on a tumor surface. Narrow-band imaging (NBI) is dark in observing whole gastric mucosa and poor at visualizing mucosal microstructure. Blue laser imaging (BLI) has the potential to resolve these limitations. Narrow-band laser light combined with white light shows irregular microvessels on both differentiated and undifferentiated gastric cancer similar to those using NBI. In addition, irregular surface patterns including minute white zones are clearly seen on the uneven surface of differentiated lesions, resulting in exclusion of undifferentiated lesions. Using both distant and close-up views, a high contrast between green intestinal metaplasia and brown gastric cancer may lead to early detection of gastric cancers and determination of a demarcation line. BLI produces high-contrast images in esophageal cancer with clear vision of intrapapillary capillary loops and also predicts the histopathological diagnosis and depth of invasion in colorectal neoplasms.

A case of delayed bleeding of the chest wall after VATS treated with transcatheter arterial embolization.

We report a case of delayed bleeding after video-assisted thoracic surgery (VATS) that was successfully treated with transcatheter arterial embolization. An 81-year-old woman underwent a pleural biopsy via VATS for pleural dissemination of lung cancer. The postoperative course was good, but 8 days later she was hospitalized for swelling in the right axilla and was admitted to our hospital with a diagnosis of delayed postoperative hemorrhage. Gauze compression was performed, and the patient was discharged without exacerbation of hematoma. However, 4 days later, she was hospitalized for rapidly worsening swelling and pain. Chest computed tomography at the time of rebleeding showed an increase in the hematoma and extravasation in the peripheral right lateral thoracic artery. The patient was immediately treated with emergency angiography, and coil embolization was performed. After this treatment, the patient has done well and there has been no subsequent recurrence of bleeding.

Safety of Readministration of EGFR-TKI After Onset of Interstitial Lung Disease in Advanced EGFR-Mutated NSCLC: A Systematic Review and Meta-Analysis.

BACKGROUND: In patients with epidermal growth factor receptor (EGFR) mutated non-small-cell lung cancer (NSCLC), EGFR-tyrosine kinase inhibitor (TKI) interruption due to EGFR-TKI-induced interstitial lung disease (ILD) is a factor for shorter overall survival (OS). Several retrospective cohort studies have reported an OS-prolonging effect of the readministration of EGFR-TKIs. This study aimed to determine the safety of readministration of EGFR-TKIs after the onset of EGFR-TKI-induced ILD. METHODS: The PubMed, CINAHL, and Web of Science databases were systematically searched until May 30, 2023. The primary outcome was successful readministration of EGFR-TKIs after the onset of EGFR-TKI-induced ILD. RESULTS: A total of 690 patients were included in this meta-analysis. The initial EGFR-TKI-induced ILD rate was 13.6% (95% confidence interval [CI]:6.4-20.9). Readministration rate of EGFR-TKI after onset of EGFR-TKI-induced ILD was 40.2% (95% CI: 26.7-53.7). The successful readministration rate of EGFR-TKIs after onset of EGFR-TKI-induced ILD was 81.9% (95% CI: 73.8-90.0). Successful rate of EGFR-TKI readministration in patients with Grade 2 or higher adverse events post initial EGFR-TKI therapy was 76.1% (95% CI: 55.6-96.6). CONCLUSIONS: Although initial EGFR-TKI-induced ILD has a relatively high incidence, EGFR-TKI readministration after the onset of EGFR-TKI-induced ILD may be a viable treatment option.