Exploring Neuroprotective Effects of Topical Brimonidine in Experimental Diabetic Retinopathy.

BACKGROUND/AIM: Diabetic retinopathy is a leading cause of blindness worldwide, characterized by neurovascular dysfunction. This study aimed to investigate the impact of brimonidine, a selective adrenoceptor agonist, on diabetic retinal neurodegeneration, recognizing the critical role of neurodegeneration in diabetic retinopathy. MATERIALS AND METHODS: Streptozotocin-induced diabetes was established in adult male Sprague-Dawley rats to mimic diabetic retinopathy. Rats, except non-diabetic control rats, received topical applications of 0.15% brimonidine tartrate (treatment group) or balanced salt solution (diabetic control group) twice daily following diabetes induction. Each group comprised six randomly assigned animals. Retinal samples were analyzed using immunofluorescence staining, apoptosis assay, and western blot. RESULTS: Topical brimonidine treatment reduced apoptosis of retinal ganglion cells at 8 weeks after induction of diabetes (p<0.05). Glial activation induced by diabetes was reduced by brimonidine treatment. Immunoblot and immunofluorescence assay revealed that the decrease in phospho- protein kinase B (AKT) level resulting from diabetes was also attenuated by brimonidine (p<0.05). Furthermore, brimonidine alleviated the decrease in anti-apoptotic proteins [BCL2 apoptosis regulator (BCL2) and BCL-xl] induced by diabetes (p<0.05). Elevation of phospho-p38 mitogen-activated protein kinase (p38MAPK) and p53 in diabetic rats were reduced by brimonidine (p<0.05). Additionally, brimonidine treatment attenuated the upregulation of the pro-apoptotic molecule BCL-2 associated X in retinas of diabetic rats (p<0.05). CONCLUSION: These findings suggest that topical brimonidine treatment may protect retinal ganglion cells in experimental diabetes by modulating the AKT pathway and reducing pro-apoptotic p38MAPK levels. This presents a potential neuroprotective approach in diabetes, offering the advantage of localized treatment without the added burden of oral medication.

Motion-Accommodating Dual-Layer Hydrogel Dressing to Deliver Adipose-Derived Stem Cells to Wounds.

BACKGROUND: Current dressing materials cannot secure a cell survival-promoting wound environment for stem cell delivery due to insufficient assimilation to skin motion. The authors developed a novel motion-accommodating dual-layer hydrogel dressing for stem cell delivery into such wounds. METHODS: Dorsal hand skin movement was evaluated to determine the potential range of deformation for a dressing. The outer hydrogel (OH) was fabricated with an alginate-acrylamide double-network hydrogel with a covalently cross-linked elastomer coat. The tough adhesive consisted of a chitosan-based bridging polymer and coupling reagents. OH material properties and adhesiveness on porcine skin were measured. An oxidized alginate-based inner hydrogel (IH) containing human adipose-derived stem cells (ASCs) was evaluated for cell-supporting and cell-releasing properties. The OH's function as a secondary dressing, and dual-layer hydrogel cell delivery potential in wounds were assessed in a rodent model. RESULTS: The dual-layer hydrogel consisted of OH and IH. The OH target range of deformation was up to 25% strain. The OH adhered to porcine skin, and showed significantly higher adhesion energy than common secondary dressings and endured 900 flexion-extension cycles without detachment. OH showed a similar moisture vapor transmission rate as moisture-retentive dressings. IH maintained embedded cell survival for three days with significant cell release on the contacting surface. OH showed less fibrotic wound healing than other secondary dressings in vivo. The dual-layer hydrogel successfully delivered ASCs into open wounds of nude mice (13 ± 3 cells/HPF). CONCLUSIONS: The novel dual-layer hydrogel can accommodate patient movement and deliver ASCs into the wound bed by securing the wound microenvironment.

A Modified eCura System to Stratify the Risk of Lymph Node Metastasis in Undifferentiated-Type Early Gastric Cancer After Endoscopic Resection.

PURPOSE: The original eCura system was designed to stratify the risk of lymph node metastasis (LNM) after endoscopic resection (ER) in patients with early gastric cancer (EGC). We assessed the effectiveness of a modified eCura system for reflecting the characteristics of undifferentiated-type (UD)-EGC. MATERIALS AND METHODS: Six hundred thirty-four patients who underwent non-curative ER for UD-EGC and received either additional surgery (radical surgery group; n=270) or no further treatment (no additional treatment group; n=364) from 18 institutions between 2005 and 2015 were retrospectively included in this study. The eCuraU system assigned 1 point each for tumors >20 mm in size, ulceration, positive vertical margin, and submucosal invasion <500 µm; 2 points for submucosal invasion ≥500 µm; and 3 points for lymphovascular invasion. RESULTS: LNM rates in the radical surgery group were 1.1%, 5.4%, and 13.3% for the low- (0-1 point), intermediate- (2-3 points), and high-risk (4-8 points), respectively (P-for-trend<0.001). The eCuraU system showed a significantly higher probability of identifying patients with LNM as high-risk than the eCura system (66.7% vs. 22.2%; McNemar P<0.001). In the no additional treatment group, overall survival (93.4%, 87.2%, and 67.6% at 5 years) and cancer-specific survival (99.6%, 98.9%, and 92.9% at 5 years) differed significantly among the low-, intermediate-, and high-risk categories, respectively (both P<0.001). In the high-risk category, surgery outperformed no treatment in terms of overall mortality (hazard ratio, 3.26; P=0.015). CONCLUSIONS: The eCuraU system stratified the risk of LNM in patients with UD-EGC after ER. It is strongly recommended that high-risk patients undergo additional surgery.

Wnt/ß-catenin pathway is a key signaling pathway to trastuzumab resistance in gastric cancer cells.

BACKGROUND: Trastuzumab is the only approved target agent for the first-line treatment of human epidermal growth factor receptor-2 (HER-2) positive gastric cancer; however, trastuzumab resistance is a major problem in clinical practice. To comprehend the mechanism of trastuzumab resistance, we focused on the Wnt/ß-catenin signaling pathway and its influence on the phenotypes and behavior of trastuzumab-resistant gastric cancer cells. METHODS: Trastuzumab-resistant NCI-N87R cells were established in vitro from the human gastric cancer cell line NCI-N87 by dose-escalating repeated trastuzumab treatment. We investigated the phenotypes of NCI-N87R cells, including Wnt signaling pathway activity. Gastric cancer organoid cells were incubated with complete medium and Wnt3a-depletion medium, and their resistance to trastuzumab was compared. RESULTS: NCI-N87R exhibited stemness and epithelial-mesenchymal transition (EMT)-like phenotypes, along with decreased levels of the epithelial marker E-cadherin and increased levels of the mesenchymal markers Vimentin and Snail along with an increased Wnt signaling pathway activity. When gastric cancer cells were incubated in Wnt3a-conditioned medium. Wnt signaling pathway activity and resistance to trastuzumab increased. Gastric cancer patient-derived organoids incubated in Wnt3a-depletion medium were more susceptible to dose-dependent inhibition of cell viability by trastuzumab than those incubated in complete medium. CONCLUSIONS: Trastuzumab-resistant gastric cancer cells exhibited EMT-like phenotype, and trastuzumab resistance was promoted by the Wnt/ß-catenin signaling pathway. The Wnt/ß-catenin pathway is a key signaling pathway for trastuzumab resistance in gastric cancer cells.

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.

External Validation of the eCura System for Undifferentiated-Type Early Gastric Cancer with Noncurative Endoscopic Resection.

Background/Aims: The eCura system, a scoring model for stratifying the lymph node metastasis risk after noncurative endoscopic resection for early gastric cancer (EGC), has been internally validated, primarily for differentiated-type EGC. We aimed to externally validate this model for undifferentiated-type EGC. Methods: This multicenter, retrospective cohort study included 634 patients who underwent additional surgery (radical surgery group, n=270) or were followed up without additional treatment (no additional treatment group, n=364) after noncurative endoscopic resection for undifferentiated-type EGC between 2005 and 2015. The lymph node metastasis and survival rates were compared according to the risk categories. Results: For the radical surgery group, the lymph node metastasis rates were 2.6%, 10.9%, and 14.8% for the low-, intermediate-, and high-risk eCura categories, respectively (p for trend=0.003). For the low-, intermediate-, and high-risk categories in the no additional treatment group, the overall survival (92.7%, 68.9%, and 80.0% at 5 years, respectively, p<0.001) and cancer-specific survival rates (99.7%, 94.7%, and 80.0% at 5 years, respectively, p<0.001) differed significantly. In the multivariate analysis, the hazard ratios (95% confidence interval) in the no additional treatment group relative to the radical surgery group were 3.18 (1.41 to 7.17; p=0.005) for overall mortality and 2.60 (0.46 to 14.66; p=0.280) for cancer-specific mortality in the intermediate-to-high risk category. No such differences were noted in the low-risk category. Conclusions: The eCura system can be applied to undifferentiated-type EGC. Close follow-up without additional treatment might be considered for low-risk patients, while additional surgery is recommended for intermediate- and high-risk patients.

Risk of Metabolic Syndrome and Fatty Liver Diseases in Gastric Cancer Survivors: A Propensity Score-Matched Analysis.

Background/Aims: To investigate the risk of metabolic syndrome and fatty liver diseases in gastric cancer survivors compared to non-cancer subjects. Methods: The data from the health screening registry of the Gangnam Severance Hospital from 2014-2019 was used. Ninety-one gastric cancer survivors and a propensity-score-matching 445 non-cancer subjects were analyzed. Gastric cancer survivors were divided into those with surgical treatment (OpGC, n=66) and non-surgical treatment (non-OpGC, n=25). Metabolic syndrome, fatty liver by ultrasonography, and metabolic dysfunction-associated fatty liver disease (MAFLD) were assessed. Results: Metabolic syndrome was in 15.4% of gastric cancer survivors (OpGC; 13.6%, non-OpGC; 20.0%). Fatty liver by ultrasonography was in 35.2% in gastric cancer survivors (OpGC; 30.3%, non-OpGC: 48.0%). MAFLD was in 27.5% of gastric cancer survivor (OpGC; 21.2%, non-OpGC; 44.0%). After adjusting for age, sex, smoking, and alcohol, the risk of metabolic syndrome was lower in OpGC than in non-cancer subjects (OR, 0.372; 95% CI, 0.176-0.786, p=0.010). After adjusting, OpGC showed lower risks of fatty liver by ultrasonography (OR, 0.545; 95% CI, 0.306-0.970, p=0.039) and MAFLD (OR, 0.375; 95% CI, 0.197-0.711, p=0.003) than did non-cancer subjects. There were no significant differences in the risks of metabolic syndrome and fatty liver diseases between non-OpGC and non-cancer subjects. Conclusions: OpGC showed lower risks of metabolic syndrome, fatty liver by ultrasonography, and MAFLD than non-cancer subjects, but there were no significant differences in the risks between non-OpGC and non-cancer subjects. Further studies on metabolic syndrome and fatty liver diseases in gastric cancer survivors are warranted.

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.

Association of Waist Circumference with the Risk of Inflammatory Bowel Disease: a Nationwide Cohort Study of 10 Million Individuals in Korea.

BACKGROUND AND AIMS: Metabolic syndrome may share the pathophysiology of adipose tissue dysregulation and inadequate immune response with inflammatory bowel disease [IBD]. We determined the association of abdominal obesity [AO] with the risk of developing IBD. METHODS: We conducted a nationwide population-based cohort study using the Korean National Health Insurance Services database. A total of 10 082 568 participants of the 2009 national health screening programme were enrolled. Newly diagnosed Crohn's disease [CD] and ulcerative colitis [UC] were identified using the International Classification of Diseases 10th Revision and specialized national codes for rare intractable diseases. Waist circumference [WC] was classified into six groups and compared with the reference values of 85.0-89.9 cm for men and 80.0-84.9 cm for women. AO was defined as a WC of ≥90 cm for men and ≥85 cm for women. RESULTS: During a median follow-up of 9.3 years, the incidence rates of CD and UC were 2.11 and 8.40 per 100 000 person-years, respectively. After adjustment for age, sex, lifestyle behaviours, income and body mass index [BMI], the increase in baseline WC was significantly associated with the risk of developing CD, but not UC, compared to the references. The risk of developing CD in subjects with AO increased significantly compared to those without AO [adjusted hazard ratio, 1.40; 95% confidence interval, 1.21-1.61], regardless of obesity based on BMI. CONCLUSIONS: Individuals with AO bore an increased risk of developing CD proportional to WC, but not UC, suggesting that visceral adiposity is related to the pathophysiology of CD.

Randomized controlled trial to evaluate the efficacy and safety of fexuprazan compared with esomeprazole in erosive esophagitis.

BACKGROUND: Fexuprazan, a novel potassium-competitive acid blocker, reversibly suppresses the K+/H+-ATPase enzyme in proton pumps within gastric parietal cells. Fexuprazan's suppression of gastric acid was maintained in healthy individuals for 24 h in a dose-dependent manner. AIM: To compare fexuprazan to esomeprazole and establish its efficacy and safety in patients with erosive esophagitis (EE). METHODS: Korean adult patients with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg or esomeprazole 40 mg once daily for eight weeks. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy at week 8. The secondary endpoints included the healing rate of EE at week 4, symptom response, and quality of life assessment. Safety profiles and serum gastrin levels were compared between the groups. RESULTS: Of the 263 randomized, 218 completed the study per protocol (fexuprazan 40 mg, n = 107; esomeprazole 40 mg, n = 111). Fexuprazan was non-inferior to esomeprazole regarding the healing rate at week 8 [99.1% (106/107) vs 99.1% (110/111)]. There were no between-group differences in the EE healing rate at week 4 [90.3% (93/103) vs 88.5% (92/104)], symptom responses, and quality of life assessments. Additionally, serum gastrin levels at weeks 4 and 8 and drug-related side effects did not significantly differ between the groups. CONCLUSION: Fexuprazan 40 mg is non-inferior to esomeprazole 40 mg in EE healing at week 8. We suggest that fexuprazan is an alternative promising treatment option to PPIs for patients with EE.

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.

Comparison of long-term outcomes of endoscopic submucosal dissection and surgery for undifferentiated-type early gastric cancer meeting the expanded criteria: a systematic review and meta-analysis.

BACKGROUND: There have been concerns over the long-term outcomes of endoscopic submucosal dissection (ESD) for undifferentiated-type early gastric cancer (UD EGC). We aimed to compare the long-term outcomes of ESD and surgery for patients with UD EGC. METHODS: We searched PubMed, Embase, and Cochrane Library databases through March 2021 to identify studies that compared the long-term outcomes of ESD and surgery for UD EGC meeting expanded criteria for curative resection. The risk of bias was assessed with the Cochrane tool for non-randomized studies. The risk ratio (RR) was estimated using a fixed-effect model. RESULTS: Overall, 1863 patients from five retrospective cohort studies, including 908 patients with propensity score matching (PSM), were eligible for meta-analysis. ESD was associated with inferior overall survival (OS) compared to surgery in the overall cohort (RR 2.11; 95% CI 1.26-3.55) but not in the PSM cohort (RR 1.18; 95% CI 0.60-2.32). In the PSM cohort, ESD had a lower disease-free survival (DFS) (RR 2.49; 95% CI 1.42-4.35) and higher recurrence (RR 12.61; 95% CI 3.43-46.37), gastric recurrence (RR 11.25; 95% CI 3.06-41.40), and extragastric recurrence (RR 4.23; 95% CI 0.47-37.93). Recurrence outcomes were similar between the overall and PSM cohorts. Disease-specific survival was not significantly different between the two groups in both the overall and PSM cohorts. CONCLUSION: Although OS after curative ESD for UD EGC was not different from that after surgery in the PSM cohort, DFS and recurrence were inferior after ESD. Limitations included a lack of randomized trials. Further prospective studies comparing the long-term outcomes of ESD and surgery for UD EGC are needed (PROSPERO CRD 42021237097).

Association between triglyceride-glucose index and gastric carcinogenesis: a health checkup cohort study.

BACKGROUND: We aimed to investigate the association between the triglyceride-glucose (TyG) index and gastric carcinogenesis, including precancerous conditions such as dysplasia, atrophic gastritis, and intestinal metaplasia. METHODS: Patients who received an upper endoscopic assessment at a medical center were included. The enrolled patients were divided into four categories according to their TyG index quartile (Q). To evaluate the relationship between increase of TyG index and gastric cancer, we analyzed the patients who received a health checkup twice. Moreover, receiver-operating characteristic curve analysis was used to establish cut-off value of the TyG index for gastric cancer. RESULTS: Of 127,564 enrolled patients, 43,525 (34.1%) and 186 (0.1%) were diagnosed with precancerous conditions and gastric cancer, respectively. The odds ratios (ORs) of precancerous conditions given TyG index progressively increased across quartiles: using Q1 as the reference: Q2 (OR = 1.403, P < 0.001), Q3 (OR = 1.646, P < 0.001), and Q4 (OR = 1.656, P < 0.001). The ORs of gastric cancer also increased according to the quartiles: Q2 (OR = 1.619, P = 0.045), Q3 (OR = 2.180, P = 0.004), and Q4 (OR = 2.363, P = 0.001). Moreover, the increase in TyG index between baseline and follow-up tests was more significant in gastric cancer group than in control group (P = 0.001). The optimal cut-off value for predicting gastric cancer was 9.73. CONCLUSIONS: The TyG index may be a novel predictive biomarker for gastric carcinogenesis. Notably, increase in the TyG index is significantly associated with gastric cancer.