Efficacy of Tegoprazan in Patients With Functional Dyspepsia: A Prospective, Multicenter, Single-arm Study.

Background/Aims: Acid-suppressive drugs, such as proton pump inhibitors (PPIs), are treatment options for functional dyspepsia (FD). However, the efficacy of potassium-competitive acid blockers (P-CABs) in treating FD has not yet been established. This prospective multicenter clinical trial-based study aimed to assess the efficacy and safety of tegoprazan as a P-CAB treatment in patients with FD. Methods: FD was diagnosed using the Rome IV criteria. All patients received tegoprazan 50 mg once daily for 8 weeks. Dyspeptic symptoms were assessed using a dyspepsia symptom questionnaire (5-point Likert scale, Nepean Dyspepsia Index-Korean (NDI-K), and gastroesophageal reflux disease-health-related quality of life (GERD-HRQL). The main outcome was satisfactory symptom relief rates at 8 weeks. Results: In this study, from the initial screening of 209 patients, 173 were included in the per-protocol set analysis. Satisfactory symptom relief rates at 8 and 4 weeks were 86.7% and 74.6%, respectively. In addition, the NDI-K and GERD-HRQL scores significantly improved at 8 and 4 weeks compared with the baseline scores. The efficacy of tegoprazan was not influenced by the FD subtype or Helicobacter pylori status. In patients with overlapping FD and GERD, there was a greater improvement in the NDI-K and GERD-HRQL scores than in patients with FD symptoms only. No serious drug-related adverse events occurred during this study. Conclusion: Tegoprazan (50 mg) administered once daily provided satisfactory symptom relief for FD.

Expression of Immunoglobulin G4 in Eosinophilic Esophagitis.

Background: Eosinophilic esophagitis (EoE) is a disease that has been subcategorized into two endoscopic phenotypes: inflammatory and fibrostenotic. Moreover, studies have shown a link between EoE and immunoglobulin G4 (IgG4), a subclass of the immunoglobulin G (IgG) antibody. In this study, we aimed to evaluate the relationship between histologic IgG4 expression and endoscopic phenotypes in patients with EoE. Methods: This case-control study included patients diagnosed with EoE (n = 19) and patients with non-obstructive dysphagia without abnormal findings as controls (NOD; n = 12). The EoE group was further divided into three subgroups based on endoscopic phenotype: inflammatory, fibrostenotic, or combined. Retrospective examination of endoscopic findings and pathological slides was performed to analyze IgG4 staining. Results: Histological analysis revealed a significant difference in IgG4 cell count (15.00 vs. 0.58, p = 0.003) and eosinophil cell count (84.67 vs. 0.08, p < 0.001) between the EoE and NOD groups. Symptom manifestation and blood test results were similar across all three endoscopic EoE phenotypes. However, histological analysis revealed a significant difference in IgG4 cell count between the inflammatory, fibrostenotic, and combined phenotypes (4.13 vs. 17.6 vs. 59.7, p = 0.030). Conclusions: IgG4 expression was higher in EoE patients than in those with NOD, the highest being in the combined phenotype subgroup. These findings emphasize the important role of endoscopic and histological examination in diagnosing EoE and the need for further research in this area.

The Effect of Tegoprazan on the Treatment of Endoscopic Resection-Induced Artificial Ulcers: A Multicenter, Randomized, Active-Controlled Study.

Background/Aims: : Tegoprazan is a novel potassium-competitive acid blocker that has beneficial effects on acid-related disorders such as gastroesophageal reflux and peptic ulcer diseases. This study aimed to validate the effect of tegoprazan on endoscopic submucosal dissection (ESD)-induced artificial ulcers. Methods: : Patients from 16 centers in Korea who underwent ESD for gastric neoplasia were enrolled. After ESD, pantoprazole was administered intravenously for 48 hours. The patients were randomly allocated to either the tegoprazan or esomeprazole group. Tegoprazan 50 mg or esomeprazole 40 mg were administered for 4 weeks, after which gastroscopic evaluation was performed. If the artificial ulcer had not healed, the same dose of tegoprazan or esomeprazole was administered for an additional 4 weeks, and a gastroscopic evaluation was performed. Results: : One hundred sixty patients were enrolled in this study. The healing rates of artificial ulcers at 4 weeks were 30.3% (23/76) and 22.1% (15/68) in the tegoprazan and esomeprazole groups, respectively (p=0.006). At 8 weeks after ESD, the cumulative ulcer healing rates were 73.7% (56/76) and 77.9% (53/68) in the tegoprazan and esomeprazole groups, respectively (p=0.210). Delayed bleeding occurred in two patients in the tegoprazan group (2.6%) and in one patient in the esomeprazole group (1.5%). Other adverse events were negligible in both groups. Conclusions: : Tegoprazan showed similar effects on post-ESD artificial ulcer healing in comparison with esomeprazole.

Clinical Trial: Efficacy of Mosapride Controlled-release and Nortriptyline in Patients With Functional Dyspepsia: A Multicenter, Double-placebo, Double-blinded, Randomized Controlled, Parallel Clinical Study.

Background/Aims: Prokinetic agents and neuromodulators are among the treatment options for functional dyspepsia (FD), but their comparative efficacy is unclear. We aimed to compare the efficacy of mosapride controlled-release (CR) and nortriptyline in patients with FD after 4 weeks of treatment. Methods: Participants with FD were randomly assigned (1:1) to receive mosapride CR (mosapride CR 15 mg and nortriptyline placebo) or nortriptyline (mosapride CR placebo and nortriptyline 10 mg) in double-placebo, double-blinded, randomized controlled, parallel clinical study. The primary endpoint was defined as the proportion of patients with overall dyspepsia improvement after 4 weeks treatment. The secondary endpoints were changes in individual symptom scores, anxiety, depression, and quality of life. Results: One hundred nine participants were recruited and assessed for eligibility, and 54 in the mosapride CR group and 50 in the nortriptyline group were included in the modified intention-to-treat protocol. The rate of overall dyspepsia improvement was similar between groups (53.7% vs 54.0%, P = 0.976). There was no difference in the efficacy of mosapride CR and nortriptyline in a subgroup analysis by FD subtype (59.3% vs 52.5% in postprandial distress syndrome, P = 0.615; 44.4% vs 40.0% in epigastric pain syndrome, P = > 0.999; 50.0% vs 59.1% in overlap, P = 0.565; respectively). Both treatments significantly improved anxiety, depression, and quality of life from baseline. Conclusion: Mosapride CR and nortriptyline showed similar efficacy in patients with FD regardless of the subtype. Both treatments could be equally helpful for improving quality of life and psychological well-being while also relieving dyspepsia.

Potential risk of proton pump inhibitors for Parkinson's disease: A nationwide nested case-control study.

Proton pump inhibitor (PPI) use is a potential risk factor for neurodegenerative disease development; however, its role in Parkinson's disease (PD) remains unclear. This study aimed to investigate the association between PPI use and PD risk. A total of 31,326 patients with newly diagnosed PD were matches by age, sex, body mass index, diabetes, and hypertension with 125,304 controls at a ratio of 1:4. The data were collected from the Korean National Health Insurance Services Database from January 2010 to December 2019. Cumulative defined daily doses of PPIs were extracted from treatment claims. We examined the association between PPI use and PD risk using conditional logistic regression. To prevent protopathic bias, we excluded patients diagnosed with PD within a 1-year lag period after PPI exposure. We applied 2- and 3-year lag periods for sensitivity analysis. PPI use was associated with an increased risk of PD when a 1-year lag period was applied between PPI exposure and PD development (adjusted odds ratio, 1.10; 95% confidence interval, 1.07-1.13). A significant positive dose-response relationship existed between the cumulative defined daily doses of PPIs and PD development (P<0.001). Similar results were obtained for the 2- or 3-year lag periods. The association did not vary based on gender. Older age, a higher Charlson Comorbidity Index score, no alcohol consumption, and a non-smoking status were associated with a significantly increased PD risk with PPI use. We observed an association between PPI use and PD risk, although long-term follow-up studies are necessary to verify this association.

On-demand Versus Continuous Maintenance Treatment With a Proton Pump Inhibitor for Mild Gastroesophageal Reflux Disease: A Prospective Randomized Multicenter Study.

Background/Aims: It remains unclear which maintenance treatment modality is most appropriate for mild gastroesophageal reflux disease (GERD). We aimed to compare on-demand treatment with continuous treatment using a proton pump inhibitor (PPI) in the maintenance treatment for patients with non-erosive GERD or mild erosive esophagitis. Methods: Patients whose GERD symptoms improved after 4 weeks of standard dose PPI treatment were prospectively enrolled at 25 hospitals. Subsequently, the enrolled patients were randomly assigned to either an on-demand or a continuous maintenance treatment group, and followed in an 8-week interval for up to 24 weeks. Results: A total of 304 patients were randomized to maintenance treatment (continuous, n = 151 vs on-demand, n = 153). The primary outcome, the overall proportion of unwillingness to continue the assigned maintenance treatment modality, failed to confirm the non-inferiority of on-demand treatment (45.9%) compared to continuous treatment (36.1%). Compared with the on-demand group, the GERD symptom and health-related quality of life scores significantly more improved and the overall satisfaction score was significantly higher in the continuous treatment group, particularly at week 8 and week 16 of maintenance treatment. Work impairment scores were not different in the 2 groups, but the prescription cost was less in the on-demand group. Serum gastrin levels significantly elevated in the continuous treatment group, but not in the on-demand group. Conclusions: Continuous treatment seems to be more appropriate for the initial maintenance treatment of non-erosive GERD or mild erosive esophagitis than on-demand treatment. Stepping down to on-demand treatment needs to be considered after a sufficient period of continuous treatment.

Real-world Prescription Patterns and Patient Satisfaction Regarding Maintenance Therapy of Gastroesophageal Reflux Disease: An Observational, Cross-sectional, Multicenter Study.

Background/Aims: Gastroesophageal reflux disease (GERD) is a common chronic gastrointestinal disorder that typically requires long-term maintenance therapy. However, little is known about patient preferences and satisfaction and real-world prescription patterns regarding maintenance therapy for GERD. Methods: This observational, cross-sectional, multicenter study involved patients from 18 referral hospitals in Korea. We surveyed patients who had been prescribed proton pump inhibitors (PPIs) for GERD for at least 90 days with a minimum follow-up duration of 1 year. The main outcome was overall patient satisfaction with different maintenance therapy modalities. Results: A total of 197 patients were enrolled. Overall patient satisfaction, patient preferences, and GERD health-related quality of life scores did not significantly differ among the maintenance therapy modality groups. However, the on-demand therapy group experienced a significantly longer disease duration than the continuous therapy group. The continuous therapy group demonstrated a lower level of awareness of potential adverse effects associated with PPIs than the on-demand therapy group but received higher doses of PPIs than the on-demand therapy group. The prescribed doses of PPIs also varied based on the phenotype of GERD, with higher doses prescribed for non-erosive reflux disease than erosive reflux disease. Conclusion: Although overall patient satisfaction did not significantly differ among the different PPI maintenance therapy modality groups, awareness of potential adverse effects was significantly different between the on-demand and continuous therapy groups.

Risk of gastric cancer among long-term proton pump inhibitor users: a population-based cohort study.

PURPOSE: To elucidate whether long-term proton pump inhibitor (PPI) users have an increased gastric cancer (GC) risk. METHODS: We searched the 2009-2019 Korean National Health Insurance Services Database for patients aged > 40 years who claimed for Helicobacter pylori eradication (HPE) during 2009-2014. The GC incidence following a PPI exposure of > 180 cumulative defined daily dose (cDDD) and that following an exposure of < 180 cDDD were compared. The outcome was GC development at least 1 year following HPE. A propensity score (PS)-matched dataset was used for analysis within the same quartiles of the follow-up duration. Additionally, dose-response associations were assessed, and the mortality rates were compared between long-term PPI users and non-users. RESULTS: After PS matching, 144,091 pairs of PPI users and non-users were analyzed. During a median follow-up of 8.3 (interquartile range, 6.8-9.6) years, 1053 and 948 GC cases in PPI users and non-users, respectively, were identified, with the GC incidence (95% confidence interval (CI)) being 0.90 (0.85-0.96) and 0.81 (0.76-0.86) per 1000 person-years, respectively. The adjusted hazard ratio (aHR) for GC with PPI use was 1.15 (95% CI, 1.06-1.25). Among PPI users, patients in the highest tertile for annual PPI dose showed higher GC development than those in the lowest tertile (aHR (95% CI): 3.87 (3.25-4.60)). GC-related mortality did not differ significantly between PPI users and non-users. CONCLUSION: In this nationwide analysis in Korea, where the GC prevalence is high, long-term PPI use after HPE showed a significant increase in GC, with a positive dose-response relationship.

Proton pump inhibitor use and the risk of metachronous gastric cancer after H. pylori eradication in patients who underwent endoscopic resection for gastric neoplasms: A population-based cohort study.

BACKGROUND: The association between proton pump inhibitors (PPI) use and gastric cancer remains controversial. AIMS: To investigate the impact of long-term PPI use on metachronous gastric cancer after Helicobacter pylori eradication in high-risk patients who underwent endoscopic resection of gastric neoplasms. METHODS: Using the Korean National Health Insurance Services database, we identified 1836 PPI users and 12,218 non-users among patients who received H. pylori eradication therapy after endoscopic resection for gastric neoplasms between 2009 and 2014. We then compared the incidence of metachronous gastric cancer between the PPI user and non-user groups. We conducted sensitivity analysis using various time lags and propensity score-matched analysis to ensure the robustness of the results. RESULTS: After a median follow-up of 7.3 years, the incidence of metachronous gastric cancer was significantly higher in the PPI user group than in the non-user group, with a crude hazard ratio of 6.20 (95% confidence interval, 5.78-6.65). After adjustment, PPI use was associated with the development of metachronous gastric cancer, with an adjusted hazard ratio of 5.51 (95% confidence interval, 5.12-5.92). The PPI user group was categorised into three subgroups according to the cumulative PPI dose; the increased risk of metachronous gastric cancer remained significant regardless of the PPI dose. Moreover, these results remained robust after applying various time lags and propensity score-matched analyses. CONCLUSIONS: Long-term PPI use is associated with an increased risk of metachronous gastric cancer in patients who undergo H. pylori eradication therapy after endoscopic resection of gastric neoplasms.

Risk of all-cause and cause-specific mortality associated with immune-mediated inflammatory diseases in Korea.

Objective: Immune-mediated inflammatory disease (IMID) is associated with an increased risk of mortality. It is unclear whether the higher mortality is attributable to the IMIDs themselves or to the higher prevalence of comorbidities in IMIDs. We aimed to investigate whether IMIDs per se confer a higher risk of mortality. Methods: From the Korean National Health Insurance Service-National Sample Cohort database, this population-based cohort study included 25,736 patients newly diagnosed with IMIDs between January 2007 and December 2017, and 128,680 individuals without IMIDs who were matched for age, sex, income, hypertension, type 2 diabetes, dyslipidemia, and the Charlson comorbidity index. All individuals were retrospectively observed through December 31, 2019. The outcomes included all-cause and cause-specific mortalities. Adjustments for age, sex, and comorbidities were performed using multivariable Cox proportional hazard regression analyses, and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) for the outcomes were estimated. Results: The adjusted risk of all-cause mortality was significantly lower in patients with IMIDs than that in those without (aHR, 0.890; 95% CI, 0.841-0.942). Regarding cause-specific mortality, cancer-specific (aHR, 0.788; 95% CI, 0.712-0.872) and cardiovascular disease-specific (aHR, 0.798; 95% CI, 0.701-0.908) mortalities were the two causes of death that showed significantly lower risks in patients with IMIDs. A similar trend was observed when organ based IMIDs were analyzed separately (i.e., gut, joint, and skin IMIDs). Conclusion: After adjusting for comorbidities, IMIDs were associated with a lower risk of all-cause mortality compared to those without IMIDs. This was attributable to the lower risks of cancer-and cardiovascular disease-specific mortalities.

Role of endoscopy in patients with achalasia.

Achalasia is an esophageal motility disorder characterized by impaired lower esophageal sphincter relaxation and peristalsis of the esophageal body. With the increasing prevalence of achalasia, interest in the role of endoscopy in its diagnosis, treatment, and monitoring is also growing. The major diagnostic modalities for achalasia include high-resolution manometry, esophagogastroduodenoscopy, and barium esophagography. Endoscopic assessment is important for early diagnosis to rule out diseases that mimic achalasia symptoms, such as pseudo-achalasia, esophageal cancer, esophageal webs, and eosinophilic esophagitis. The major endoscopic characteristics suggestive of achalasia include a widened esophageal lumen and food residue in the esophagus. Once diagnosed, achalasia can be treated either endoscopically or surgically. The preference for endoscopic treatment is increasing owing to its minimal invasiveness. Botulinum toxins, pneumatic balloon dilation, and peroral endoscopic myotomy (POEM) are important endoscopic treatments. Previous studies have demonstrated excellent treatment outcomes for POEM, with >95% improvement in dysphagia, making POEM the mainstay treatment option for achalasia. Several studies have reported an increased risk of esophageal cancer in patients with achalasia. However, routine endoscopic surveillance remains controversial owing to the lack of sufficient data. Further studies on surveillance methods and duration are warranted to establish concordant guidelines for the endoscopic surveillance of achalasia.

Association of immune-mediated inflammatory diseases with depression and anxiety in patients with type 2 diabetes: A nationwide population-based study.

Objective: Patients with type 2 diabetes (T2DM) are at a high risk of developing depression and anxiety. To better stratify the risk, we aimed to assess whether the presence of immune-mediated inflammatory diseases (IMIDs) confers a higher risk of depression and anxiety in these patients. Methods: Patients with T2DM without prior depression or anxiety who underwent national health examination between 2009 and 2012 (n = 1,612,705) were enrolled from the nationwide health check-up data from Korean National Health Insurance Service. The outcome events were incident depression and anxiety, defined as International Classification of Diseases, 10th Revision codes F32-F33 and F40-F41, respectively. Multivariable Cox proportional hazard regression analyses were conducted to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) according to the existence of IMIDs. Results: Over an average follow-up time of 6.4 years, existence of gut IMIDs was associated with a higher risk of depression (aHR: 1.28 [95% CI: 1.08-1.53]) and anxiety (1.22 [1.06-1.42]). Existence of joint IMIDs was associated with a higher risk of depression (1.34 [1.31-1.37]) and anxiety (1.31 [1.29-1.34]). Existence of skin IMID was associated with a higher risk of depression (1.18 [1.14-1.23]) and anxiety (1.13 [1.09-1.16]). The effect sizes of IMIDs on depression and anxiety were larger in those with ≥ 2 IMIDs (1.42 [1.19-1.69] and 1.49 [1.29-1.72], respectively) than in those with one IMID (1.30 [1.27-1.32] and 1.26 [1.24-1.28], respectively). Conclusion: In patients with T2DM, presence of IMIDs was associated with a higher risk of depression and anxiety. More stringent attention and screening for anxiety and depression should be encouraged in patients with T2DM and comorbid IMIDs due to clinical implications of psychological distress on patient-reported outcomes and prognosis.

Nomogram for pre-procedural prediction of non-curative endoscopic resection in patients with early gastric cancer.

BACKGROUND: Non-curative resection (non-CR) after endoscopic submucosal dissection (ESD) requires additional surgery due to the possibility of lymph node metastasis (LNM). Therefore, it is important to accurately predict the risk of non-CR to avoid unnecessary preoperative procedures. Thus, we aimed to develop and verify a nomogram to predict the risk of non-CR prior to ESD. METHODS: Patients who underwent ESD for early gastric cancer (EGC) were divided into CR and non-CR groups based on the present ESD criteria. The pre-procedural factors, such as endoscopic features, radiologic findings, and pathology of the lesion, were compared between the groups to identify the risk factors associated with non-CR. A nomogram was developed using multivariate analysis, and its predictive value was assessed using an external validation group. RESULTS: Among 824 patients, 682 were curative (82.7%) and 142 were non-curative (17.3%). By comparing two groups, endoscopic features including redness, whitish mucosal change, fold convergence, and large lesion size; histologic features such as moderately or poorly differentiated or signet ring cell carcinoma; and abnormal CT findings including non-specific lymph node enlargement and fold thickening were identified as significant predictors of non-CR. The nomogram was developed based on these predictors and showed good predictive performance in the external validation, with an area under the curve of 0.87. CONCLUSIONS: We developed a nomogram to predict the risk of non-CR prior to ESD. These predictive factors in addition to the existing ESD criteria can help provide the best treatment option for patients with EGC.

Relieving Anxiety Through Virtual Reality Prior to Endoscopic Procedures.

PURPOSE: Endoscopic procedures can cause anxiety, which can lead to more uncomfortable, difficult, and incomplete procedures, in addition to greater use of sedative medication. Here, we investigate whether exposing patients to virtual reality (VR) prior to endoscopic procedures can reduce their anxiety levels. MATERIALS AND METHODS: Forty patients at Gangnam Severance Hospital were enrolled and divided into the VR group and the control group. Patients in the VR group were exposed to VR prior to their procedure to alleviate anxiety. The primary data outcomes were State-Trait Anxiety Inventory (STAI), pain score, satisfaction with sedation, and satisfaction with the procedure. RESULTS: The mean STAI-state and STAI-trait did not differ significantly between the control group and the VR group. While defining a high anxiety STAI score as ≥45 in an STAI-state, the proportion of patients with high anxiety at baseline was 35% and increased to 50% prior to the procedure in the control group. However, in the VR group, the proportion of patients with high anxiety at baseline was 60% and decreased to 50% prior to the procedure. The proportion changes of patients with high anxiety in the STAI-state exhibited a significant difference between the control and VR groups (p=0.007). Furthermore, patients' satisfaction with sedation was significantly greater in the VR group compared to the control group (p=0.017). CONCLUSION: VR exposure may relieve patients' anxiety levels prior to endoscopic procedures, but further well-designed placebo-controlled studies are needed. VR, an inexpensive, easily available, and non-invasive method, also improved the satisfaction with sedation of endoscopic procedures.

Triglyceride-glucose index is associated with gastroesophageal reflux disease and erosive reflux disease: a health checkup cohort study.

The triglyceride-glucose (TyG) index was proposed as a useful marker of metabolic syndrome. Insulin resistance, the main mechanism underlying metabolic syndrome, is related to gastroesophageal reflux disease (GERD). This study aimed to elucidate the association between the TyG index and GERD/erosive reflux disease (ERD). We retrospectively reviewed the electronic medical records of patients who underwent gastroduodenoscopy at a checkup center. The calculation of TyG index used following formula: ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). We divided the patients into four groups according to the TyG index quartile (Q). We evaluated the relationship between the alteration of the TyG index and GERD in patients who received health checkups two times. Among the 52,605 enrolled patients, 3073 (5.8%) and 434 (0.8%) were diagnosed with GERD and ERD, respectively. The odds ratios (ORs) for GERD in the TyG index progressively increased across quartiles (P < 0.001): Q2 (OR = 2.477), Q3 (OR = 3.013), and Q4 (OR = 4.027) compared with Q1, which was used as a reference, respectively. Those for ERD also progressively increased across quartiles (P < 0.001): Q2 (OR = 4.264), Q3 (OR = 4.841), and Q4 (OR = 7.390) compared with Q1, respectively. Moreover, the degree of TyG index increase during the first and second tests in the GERD group was more prominent than in the control group (P = 0.001). In conclusion, the higher TyG index was significantly associated with GERD. The TyG index may be a novel predictive biomarker of GERD and ERD.

An Optimal Artificial Intelligence System for Real-Time Endoscopic Prediction of Invasion Depth in Early Gastric Cancer.

We previously constructed a VGG-16 based artificial intelligence (AI) model (image classifier [IC]) to predict the invasion depth in early gastric cancer (EGC) using endoscopic static images. However, images cannot capture the spatio-temporal information available during real-time endoscopy-the AI trained on static images could not estimate invasion depth accurately and reliably. Thus, we constructed a video classifier [VC] using videos for real-time depth prediction in EGC. We built a VC by attaching sequential layers to the last convolutional layer of IC v2, using video clips. We computed the standard deviation (SD) of output probabilities for a video clip and the sensitivities in the manner of frame units to observe consistency. The sensitivity, specificity, and accuracy of IC v2 for static images were 82.5%, 82.9%, and 82.7%, respectively. However, for video clips, the sensitivity, specificity, and accuracy of IC v2 were 33.6%, 85.5%, and 56.6%, respectively. The VC performed better analysis of the videos, with a sensitivity of 82.3%, a specificity of 85.8%, and an accuracy of 83.7%. Furthermore, the mean SD was lower for the VC than IC v2 (0.096 vs. 0.289). The AI model developed utilizing videos can predict invasion depth in EGC more precisely and consistently than image-trained models, and is more appropriate for real-world situations.

Machine Learning Improves the Prediction Rate of Non-Curative Resection of Endoscopic Submucosal Dissection in Patients with Early Gastric Cancer.

Non-curative resection (NCR) of early gastric cancer (EGC) after endoscopic submucosal dissection (ESD) can increase the burden of additional treatment and medical expenses. We aimed to develop a machine-learning (ML)-based NCR prediction model for EGC prior to ESD. We obtained data from 4927 patients with EGC who underwent ESD between January 2006 and February 2020. Ten clinicopathological characteristics were selected using extreme gradient boosting (XGBoost) and were used to develop a ML-based model. Dataset was divided into the training and internal validation sets and verified using an external validation set. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC) were evaluated. The performance of each model was compared by using the Delong test. A total of 1100 (22.1%) patients were identified as being treated non-curatively with ESD. Seven ML-based NCR prediction models were developed. The performance of NCR prediction was highest in the XGBoost model (AUROC, 0.851; 95% confidence interval, 0.837-0.864). When we compared the prediction performance by the Delong test, XGBoost (p = 0.02) and support vector machine (p = 0.02) models showed a significantly higher performance among the NCR prediction models. We developed an ML model capable of accurately predicting the NCR of EGC before ESD. This ML model can provide useful information for decision-making regarding the appropriate treatment of EGC before ESD.

Effects of immune-mediated inflammatory diseases on cardiovascular diseases in patients with type 2 diabetes: a nationwide population-based study.

Both type 2 diabetes and immune-mediated inflammatory diseases (IMIDs), such as Crohn's disease (CD), ulcerative colitis, rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriasis (PsO) are risk factors of cardiovascular disease. Whether presence of IMIDs in patients with type 2 diabetes increases their cardiovascular risk remains unclear. We aimed to investigate the risk of cardiovascular morbidity and mortality in patients with type 2 diabetes and IMIDs. Patients with type 2 diabetes without cardiovascular disease were retrospectively enrolled from nationwide data provided by the Korean National Health Insurance Service. The primary outcome was cardiovascular mortality, and the secondary outcomes were myocardial infarction (MI), stroke, and all-cause mortality. Inverse probability of treatment weighting (IPTW)-adjusted Cox proportional hazard regression analysis was performed to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for each IMID. Overall 2,263,853 patients with type 2 diabetes were analyzed. CD was associated with a significantly higher risk of stroke (IPTW-adjusted HR: 1.877 [95%CI 1.046, 3.367]). UC was associated with a significantly higher risk of MI (1.462 [1.051, 2.032]). RA was associated with a significantly higher risk of cardiovascular mortality (2.156 [1.769, 2.627]), MI (1.958 [1.683, 2.278]), stroke (1.605 [1.396, 1.845]), and all-cause mortality (2.013 [1.849, 2.192]). AS was associated with a significantly higher risk of MI (1.624 [1.164, 2.266]), stroke (2.266 [1.782, 2.882]), and all-cause mortality (1.344 [1.089, 1.658]). PsO was associated with a significantly higher risk of MI (1.146 [1.055, 1.246]), stroke (1.123 [1.046, 1.205]) and all-cause mortality (1.115 [1.062, 1.171]). In patients with type 2 diabetes, concomitant IMIDs increase the risk of cardiovascular morbidity and mortality. Vigilant surveillance for cardiovascular disease is needed in patients with type 2 diabetes and IMIDs.

SFRP4 and CDX1 Are Predictive Genes for Extragastric Recurrence of Early Gastric Cancer after Curative Resection.

Extragastric recurrence of early gastric cancer (EGC) after curative resection is rare, but prognosis has been poor in previous reports. Recently, single patient classifier (SPC) genes, such as secreted frizzled-related protein 4 (SFRP4) and caudal-type homeobox 1 (CDX1), were associated with prognosis and chemotherapy response in stage II-III gastric cancer. The aim of our study is, therefore, to elucidate predictive factors for extragastric recurrence of EGC after curative resection, including with the expression of SPC genes. We retrospectively reviewed electronic medical records of 1974 patients who underwent endoscopic or surgical curative resection for EGC. We analyzed clinicopathological characteristics to determine predictive factors for extragastric recurrence. Total RNA was extracted from formalin-fixed, paraffin-embedded (FFPE) tumor tissue and amplified by real-time reverse transcription polymerase chain reaction to evaluate expression of SPC genes. Overall incidences of extragastric recurrence were 0.9%. In multivariate analysis, submucosal invasion (odds ratio [OR] = 6.351, p = 0.032) and N3 staging (OR = 171.512, p = 0.012) were independent predictive factors for extragastric recurrence. Mean expression of SFRP4 in extragastric recurrence (-2.8 ± 1.3) was significantly higher than in the control group (-4.3 ± 1.6) (p = 0.047). Moreover, mean expression of CDX1 in extragastric recurrence (-4.6 ± 2.0) was significantly lower than in the control group (-2.4 ± 1.8) (p = 0.025). Submucosal invasion and metastasis of more than seven lymph nodes were independent predictive factors for extragastric recurrence. In addition, SFRP4 and CDX1 may be novel predictive markers for extragastric recurrence of EGC after curative resection.

Effect of Drinking Warm Water on Esophageal Preparation Before Peroral Endoscopic Myotomy in Patients With Achalasia.

Background/Aims: Food retention, which is a characteristic observed in patients with achalasia, can interfere with peroral endoscopic myotomy (POEM). However, there is no established guideline for esophageal preparation for POEM. A previous study has shown that drinking warm water may reduce the lower esophageal sphincter pressure in patients with achalasia. This study aims to evaluate the possibility of proper preparation of POEM by instructing the patient to drink warm water. Methods: The warm water preparation was performed in 29 patients with achalasia who underwent POEM. The patients drank 1 L of warm water (60oC) the night before POEM. We evaluated the esophageal clearness and determined the preparation quality. Twentynine patients were prospectively recruited and compared to control group. The control cohort comprised achalasia patients whose endoscopic image was available from the achalasia database of our institution. A 1:2 propensity score-matched control cohort was established from the database of achalasia subjects (n = 155) to compare the outcome of the preparation. Results: In the warm water preparation group, only 1 patient (3.4%) had some solid retention, but it did not interfere with the POEM procedure. The grade of clearness (P = 0.016) and quality of preparation (P < 0.001) were significantly better in the warm water preparation group than in the matched control group. There was no any adverse event at all related to warm water preparation protocol. Conclusions: Drinking warm water dramatically reduces esophageal food retention and significantly improves the quality of esophageal preparation. This simple protocol is quite useful, safe, and cost-effective in the preparation of achalasia patients for POEM.