Interval Advanced Gastric Cancer After Negative Endoscopy.

BACKGROUND & AIMS: Esophagogastroduodenoscopy (EGD) is effective in reducing gastric cancer mortality through detection of early-stage cancer in areas with a high prevalence of gastric cancer. Although the risk of post-endoscopy advanced gastric cancer (AGC) is low, interval AGC remains a concern. We investigated the characteristics and predictors of interval AGC after negative EGD. METHODS: We included 1257 patients with gastric cancer within 6 to 36 months of a "cancer-negative" index EGD between 2005 and 2021 at a tertiary university hospital in South Korea. Observation time on the index EGD was used as a quality indicator. We compared the clinical and endoscopic characteristics and quality indicators between interval AGC and screen-detected early gastric cancer (EGC). RESULTS: Within 6 to 36 months of negative EGD, 102 AGCs (8.1%) and 1155 EGCs (91.9%) were identified. The percentage of patients with shorter observation time (<3 minutes) in the index EGD was higher in the interval AGC group than in the detected EGC group (P = .002). A multivariable analysis comparing screen-detected EGD and interval AGC was adjusted for age, sex, family history of gastric cancer, H. pylori status, endoscopic findings, and endoscopy-related factors including gastric observation time and interval time. A shorter observation time (<3 minutes) (odds ratio, 2.27; 95% confidence interval, 1.20-4.30), and interval time >2 years (odds ratio, 1.84; 95% confidence interval, 1.04-3.24) were associated with an increased risk of interval AGC. CONCLUSION: A shorter observation time during index EGD is an important predictor of interval AGC. Further, withdrawal time longer than 3 minutes may be a quality indicator for screening EGD.

Effect of renal insufficiency on the short- and long-term outcomes of endoscopic submucosal dissection for early gastric cancer: Propensity score-matched analysis.

OBJECTIVES: It is unclear whether renal insufficiency (RI) itself is a risk factor for adverse outcomes after gastric endoscopic submucosal dissection (ESD). We aimed to evaluate the safety and efficacy of gastric ESD in patients with and without RI using propensity score-matching analysis. METHODS: In all, 4775 patients with 4775 early gastric cancer lesions undergoing ESD were analyzed. 1:1 propensity score-matching was performed between patients with and without RI using 12 variables. After matching, logistic regression and survival analyses were performed for short- and long-term outcomes of ESD, respectively. RESULTS: The matching yielded 188 pairs of patients with and without RI. In both univariable and multivariable analyses, the presence of RI was not significantly associated with postprocedural bleeding (unadjusted odds ratio 1.81, 95% confidence interval 0.74-4.42; adjusted odds ratio 1.86, 95% confidence interval 0.74-4.65, respectively). When RI patients were subclassified into patients with estimated glomerular filtration rate (eGFR) 30-59 mL/min/1.73 m2 and eGFR <30 mL/min/1.73 m2 , no significant differences in bleeding rates were found compared to their matched controls in both groups. Perforation, en bloc resection, en bloc and R0 resection, and curative resection rates of RI patients were 2.1%, 98.4%, 91.0%, and 78.2%, respectively, which were comparable to those of non-RI patients. During a median follow-up of 119 months, there was no difference in gastric cancer-specific survival between patients with and without RI (P = 0.143). CONCLUSION: The outcomes of ESD were comparable in patients with and without RI. Decreased renal function itself may not be a reason to keep patients with RI from receiving gastric ESD.

Clinical characteristics and treatment outcomes of primary malignant melanoma of esophagus: a single center experience.

BACKGROUND: Primary malignant melanoma of esophagus (PMME) is an extremely rare disease with poor prognosis. We aimed to determine the clinical characteristics and treatment outcomes of patients with PMME. METHODS: We retrospectively reviewed 17 patients diagnosed with PMME in Samsung Medical Center between 2000 and 2020 with median 34 months of follow-up. Survival outcomes were analyzed with Kaplan-Meier method. RESULTS: 15 patients (88.2%) were male and the most common presenting symptom was dysphagia (9/17, 52.9%). On endoscopy, tumors were mass-forming in 15 patients (88.2%) and diffusely infiltrative in two patients (11.8%). Lesions were melanotic in 13 patients (76.5%) and amelanotic in four patients (23.5%). The most common tumor location was lower esophagus (11/17, 64.7%). The disease was metastatic at the time of diagnosis in four patients (23.5%). As for treatment, 10 patients (58.8%) underwent surgery. In all 17 patients, the median overall survival was 10 months. In surgically treated patients, all patients experienced recurrence and the median disease-free survival was 4 months. There was no statistical difference in overall survival between patients with or without surgery. Patients with diffusely infiltrative tumor morphology had better overall survival compared to those with mass-forming tumor morphology (P = 0.048). Two patients who received immunotherapy as the first-line treatment without surgery showed overall survival of 34 and 18 months, respectively. CONCLUSIONS: As radical resection for patients with PMME does not guarantee favorable treatment outcomes, novel treatment strategy is required. Further large-scale studies are warranted to determine the efficacy of immunotherapy for patients with PMME.

A preoperative risk prediction model for high malignancy potential gastrointestinal stromal tumors of the stomach.

BACKGROUND: Gastric gastrointestinal stromal tumors (GISTs) exhibit various degrees of aggression and malignant potential. However, no systematic preoperative evaluation strategy to predict the malignancy potential of gastric GISTs has yet been developed. This study aimed to develop a reliable and easy-to-use preoperative risk-scoring model for predicting high malignancy potential (HMP) gastric GISTs. METHODS: The data of 542 patients with pathologically confirmed gastric GISTs who underwent resection were reviewed. Multivariate logistic regression analysis was used to identify significant predictors of HMP. The risk-scoring system (RSS) was based on the predictive factors for HMP, and its performance was validated using a split-sample approach. RESULTS: A total of 239 of 542 (44.1%) surgically resected gastric GISTs had HMP. Multivariate analysis demonstrated that tumor size, location, and surface changes were independent risk factors for HMP. Based on the accordant regression coefficients, the presence of surface ulceration was assigned 1 point. Tumor sizes of 4-6 cm and > 6 cm were assigned 2 and 5 points, respectively. Two points were assigned to cardia or fundus locations. A score of 3 points was the optimal cut-off value for HMP prediction. HMP were found in 19.8% and 82.7% of the low and high-risk groups of the RSS, respectively. The area under the receiver-operating characteristic curve for predicting HMP was 0.81 (95% confidence interval (CI) 0.75-0.86). Discrimination was good after validation (0.75, 95% CI 0.69-0.81). CONCLUSION: This simple RSS could be useful for predicting the malignancy potential of gastric GISTs and may aid preoperative clinical decision making to ensure optimal treatment.

Improvement of Biological Effects of Root-Filling Materials for Primary Teeth by Incorporating Sodium Iodide.

Therapeutic iodoform (CHI3) is commonly used as a root-filling material for primary teeth; however, the side effects of iodoform-containing materials, including early root resorption, have been reported. To overcome this problem, a water-soluble iodide (NaI)-incorporated root-filling material was developed. Calcium hydroxide, silicone oil, and NaI were incorporated in different weight proportions (30:30:X), and the resulting material was denoted DX (D5~D30), indicating the NaI content. As a control, iodoform instead of NaI was incorporated at a ratio of 30:30:30, and the material was denoted I30. The physicochemical (flow, film thickness, radiopacity, viscosity, water absorption, solubility, and ion releases) and biological (cytotoxicity, TRAP, ARS, and analysis of osteoclastic markers) properties were determined. The amount of iodine, sodium, and calcium ion releases and the pH were higher in D30 than I30, and the highest level of unknown extracted molecules was detected in I30. In the cell viability test, all groups except 100% D30 showed no cytotoxicity. In the 50% nontoxic extract, D30 showed decreased osteoclast formation compared with I30. In summary, NaI-incorporated materials showed adequate physicochemical properties and low osteoclast formation compared to their iodoform-counterpart. Thus, NaI-incorporated materials may be used as a substitute for iodoform-counterparts in root-filling materials after further (pre)clinical investigation.

Long-Term Safety of Delayed Surgery After Upfront Endoscopic Resection for Early Gastric Cancer: A Propensity Matched Study.

BACKGROUND: When non-curative resection is confirmed after endoscopic resection (ER) of early gastric cancer (EGC), delayed surgery is recommended because it provides favorable survival outcomes. Long-term outcome after surgery of EGC with or without previous ER has not been evaluated. OBJECTIVE: The aim of this study was to compare the long-term oncologic safety between primary surgery and delayed surgery after ER. METHODS: Patients who had undergone curative surgery (R0) for EGC were included and were divided into primary and delayed surgery groups. Primary surgery was defined as gastrectomy without ER for EGC, whereas delayed surgery was defined as additional curative gastrectomy due to non-curative resection after ER; an average delay of 21.5 days (range 1-195) was observed. Propensity score matching was performed. The primary outcome was overall survival (OS) and the secondary outcomes were cancer-specific survival (CSS) and disease-free survival (DFS). RESULTS: After propensity score matching, 1439 patients were included, of whom 1042 (72.4%) were in the primary surgery group and 397 (27.6%) were in the delayed surgery group. The OS (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.59-1.27; p = 0.459), CSS (HR 0.47, 95% CI 0.15-1.47; p = 0.196), and DFS (HR 0.54, 95% CI 0.15-1.90; p = 0.334) were not different. CONCLUSIONS: The long-term outcomes of delayed surgery after non-curative ER for EGC were non-inferior to primary surgery. Therefore, an attempt for ER of EGC that satisfies the absolute and expanded indication seems justified for preventing gastrectomy. In case of non-curative resection after ER, additional delayed surgery should be performed.

Eradication of Helicobacter pylori infection decreases risk for dyslipidemia: A cohort study.

BACKGROUND: Previous studies have suggested a relationship between Helicobacter pylori infection and dyslipidemia; however, large-scale longitudinal studies have not elucidated this association. This study assessed the longitudinal effects of H. pylori infection and eradication on lipid profiles in a large cohort. METHODS: This cohort study included 2,626 adults without dyslipidemia at baseline, who participated in a repeated, regular health-screening examination, which included upper gastrointestinal endoscopy, between January 2009 and December 2018. The primary outcome was incident dyslipidemia at follow-up. RESULTS: During the 10,324 person-years of follow-up, participants with persistent H. pylori infection had a higher incidence rate (130.5 per 1,000 person-years) of dyslipidemia than those whose infections had been successfully controlled (98.1 per 1,000 person-years). In a multivariable model adjusted for age, sex, waist circumference, smoking status, alcohol intake, and education level, the H. pylori eradication group was associated with a lower risk of dyslipidemia than the persistent group (HR, 0.85; 95% CI, 0.77-0.95; p = 0.004). The association persisted after further adjustment for baseline levels of low-density and high-density lipoprotein cholesterol (HR, 0.87; 95% CI, 0.79-0.97; p = 0.014). CONCLUSIONS: H. pylori infection may play a pathophysiologic role in the development of dyslipidemia, whereas H. pylori eradication might decrease the risk of dyslipidemia.

Cohort study of Helicobacter pylori infection and the risk of incident osteoporosis in women.

BACKGROUND AND AIM: Previous studies suggested an association between Helicobacter pylori infection and osteoporosis; however, large-scale longitudinal studies are lacking to elucidate this association. METHODS: A cohort study of 10 482 women without osteoporosis at baseline who participated in a repeated health-screening examination including an H. pylori-specific immunoglobulin G antibody test was conducted to evaluate the association between H. pylori and osteoporosis development. Osteoporosis was diagnosed using dual-energy X-ray absorptiometry. RESULTS: During the 77 515.3 person-years of follow-up, women with H. pylori infection had a higher rate of incident osteoporosis than those who were uninfected. In a multivariable model adjusted for age, body mass index (BMI), menopausal status, smoking status, regular exercise, comorbidities (including hypertension, diabetes mellitus, dyslipidemia, stroke, or ischemic heart disease), and concomitant medications, the hazard ratio (HR) for incident osteoporosis in women with H. pylori infection compared with that in women without infection was 1.23 (95% confidence interval [CI], 1.03-1.45). The association between H. pylori and osteopenia development was also evident. In the multivariable analysis, menopause (HR, 1.68; 95% CI, 1.31-2.16) and increasing age (HR, 1.07; 95% CI, 1.06-1.08) were identified as significant risk factors for osteoporosis, whereas higher BMI (HR, 0.84; 95% CI, 0.81-0.87) was a protective factor for the risk of osteoporosis. CONCLUSIONS: In this cohort study, H. pylori infection was associated with an increased risk of osteoporosis, independent of risk factors and confounding factors.

Proton pump inhibitors use and the risk of fatty liver disease: A nationwide cohort study.

BACKGROUND AND AIM: Proton pump inhibitor (PPI)-induced hypochondria can change the composition of the gut microbiota, inducing overgrowth of small bowel bacteria, which has been suggested to promote the development of fatty liver disease through the gut-liver axis. In this study, we aimed to investigate the association between PPI use and the risk of fatty liver disease. METHODS: A retrospective cohort study was conducted using the Korean National Health Insurance Service-National Sample Cohort, a nationwide population-based representative sample, from January 1, 2002, to December 31, 2015. PPI use was identified from treatment claims and considered as a time-varying variable. RESULTS: During 1 463 556 person-years of follow-up, 75 727 patients had at least one PPI prescription, and 3735 patients developed fatty liver disease. The hazard ratio for fatty liver disease comparing PPI users with non-PPI users was 1.68 (95% confidence interval, 1.61-1.75). When adjusted for multiple confounders, including age, sex, body mass index, smoking, alcohol intake, exercise, income level, and comorbidities, the association was still significant (hazard ratio, 1.50; 95% confidence interval, 1.44-1.57). After considering the amounts of PPIs stratified by cumulative defined daily dose, the dose-response effect was observed until 180 days. Subgroup analysis also revealed that PPI use was correlated to an increased risk of fatty liver disease. CONCLUSIONS: This current national wide cohort study suggests that PPI use was associated with an increased risk of fatty liver disease compared with non-use of PPIs. Clinicians should consider fatty liver as a potential risk when prescribing PPI.

Close Observation versus Additional Surgery after Noncurative Endoscopic Resection of Esophageal Squamous Cell Carcinoma.

INTRODUCTION: After noncurative endoscopic submucosal dissection (ESD) of superficial esophageal squamous cell carcinoma (SESCC), additional esophagectomy is generally recommended. However, considering its high mortality and morbidity, it is uncertain if additional surgery improves the clinical outcomes. This study aimed to compare the clinical outcomes between patients who were observed without additional treatment and those who underwent radical esophagectomy. METHODS: A total of 52 patients with SESCC who underwent complete but noncurative ESD from January 2008 to December 2016 at the Samsung Medical Center and Asan Medical Center in Korea were retrospectively analyzed. Clinicopathologic characteristics and oncologic outcomes were compared between the observation group (n = 23) and the additional surgery group (n = 29). RESULTS: During a mean follow-up of 34.4 and 41.7 months, respectively, the rates of death (observation vs. surgery, 17.4 vs. 10.3%; p = 0.686), recurrence (observation vs. surgery, 13 vs. 17.2%; p = 1.000), and disease-specific death (observation vs. surgery, 4.3 vs. 6.9%; p = 1.000) did not significantly differ between the 2 groups. The 3-year overall survival was 86.3 and 96.4%, respectively (p = 0.776). The 3-year recurrence-free survival (observation vs. surgery, 85.0 vs. 88.7%; p = 0.960) and disease-specific survival (observation vs. surgery, 95.2 vs. 96.4%; p = 0.564) also did not significantly differ. CONCLUSIONS: The clinical outcomes of close observation of noncuratively resected SESCC are comparable to those of additional surgery, at least in the midterm. The wait-and-see strategy could be a feasible management option after noncurative ESD of SESCC in selected patients.

Nomogram to predict lymph node metastasis in patients with early gastric cancer: a useful clinical tool to reduce gastrectomy after endoscopic resection.

BACKGROUND: The indications for endoscopic dissection have been expanded to improve the quality of life of patients with early gastric cancer (EGC). This study aimed to develop a nomogram to predict the status of lymph node metastasis with the aim of avoiding unnecessary gastrectomies. METHODS: We reviewed the clinicopathological data of 10 579 patients who underwent curative resection for EGC. The nomogram was developed by multivariate analysis and was evaluated by external validation. Overall, disease-free and recurrence-free survival were compared between the gastrectomy group of 6641 patients and the endoscopic dissection group of 999 patients to show the efficacy of the nomogram. RESULTS: Multivariate analyses revealed that age, tumor size, lymphatic invasion, depth of invasion, and histologic differentiation were all significant prognostic factors for lymph node metastasis. The nomogram had good discriminatory performance, with a concordance index of 0.846. This was supported by the external validation point of 0.813. For patients with low risk of lymph node metastasis on the nomogram (≤ 3 % of the provisional value in this study), the endoscopic dissection and gastrectomy groups had comparable rates of overall (P = 0.32), disease-free (P = 0.47), and recurrence-free (P = 0.09) survival. CONCLUSIONS: We developed and validated a nomogram that predicts the risk of lymph node metastasis in EGC based on a large database. This precision nomogram is useful to avoid unnecessary gastrectomy after endoscopic dissection, which may ultimately improve the quality of life of patients with EGC.

Outcomes of endoscopic submucosal dissection for intestinal-type adenocarcinoma with anastomosing glands of the stomach.

BACKGROUND AND AIM: Gastric intestinal-type adenocarcinoma with anastomosing glands (IAAG) is characterized by architectural abnormality with frequent anastomosing glands and low-grade cytologic atypia. Clinicopathologic features and long-term outcomes of endoscopic submucosal dissection (ESD) for IAAG remain unclear. METHODS: This study included 2828 patients who underwent ESD for early gastric cancers (EGCs) (78 IAAGs [2.6%] and 2893 well-differentiated [WD] or moderately differentiated [MD] EGCs [97.4%]). Clinicopathologic features and short-term and long-term outcomes of ESD for IAAG were reviewed and compared with those for WD or MD EGCs. RESULTS: Gastric IAAGs were larger and more likely to be confined to the lamina propria than WD or MD EGCs. Histological heterogeneity, flat or depressed lesion and lateral resection margin (LRM) involvement were observed with significantly higher frequencies in IAAGs than in WD or MD EGCs. En bloc with R0 resection and curative resection rates of IAAGs were 79.5% and 73.1%, respectively, and both were significantly lower than those of WD or MD EGCs (93.8% and 82.9%). LRM involvement accounted for 57.1% of the non-curative resection cases in gastric IAAGs. Half of IAAGs with LRM involvement had a crawling pattern at tumor periphery. Among patients undergoing curative ESD for IAAG, no recurrences occurred during a median 52 months of follow-up. No lymph node metastasis was found in any of IAAG patients undergoing additional surgery after ESD. CONCLUSIONS: Gastric IAAGs have distinct clinicopathologic features from WD or MD EGCs. Given the favorable long-term outcomes after curative resection, ESD can be indicated for early gastric IAAGs.

Feasibility of Endoscopic Resection in Early Gastric Cancer with Lymphovascular Invasion.

BACKGROUND: Lymphovascular invasion (LVI) is associated with the risk of lymph node metastasis (LNM) and poor survival in gastric cancer patients; however, it is unclear whether LVI is a non-curative criteria component in all patients. We evaluated the risk factors of LNM in LVI-positive early gastric cancer (EGC) patients and identified a subgroup with a negligible LNM risk to assess the feasibility of endoscopic resection in these patients. METHODS: The clinicopathologic and survival data of patients undergoing surgery for gastric cancer were reviewed; LVI-positive EGC patients were selected. Logistic regression analysis was used to test the associations of potential risk factors with LNM, and Kaplan-Meier analysis was used to compare survival curves. RESULTS: LVI was detected in 1243 (15.5%) patients. In the multivariate logistic analysis, larger tumor size (odds ratio [OR] 1.23, 95% confidence interval [CI] 1.16-1.31; p < 0.001), presence of ulcer (OR 1.80, 95% CI 1.15-2.82; p = 0.010), undifferentiated histology (OR 1.64, 95% CI 1.25-2.16; p < 0.001), submucosal invasion (OR 2.28, 95% CI 1.38-3.76; p = 0.001), middle (OR 2.12, 95% CI 1.26-3.55; p = 0.004) or lower third location (OR 2.28, 95% CI 1.32-3.60; p = 0.002), and younger age (OR 0.98, 95% CI 0.97-0.99; p = 0.002) independently predicted LNM in LVI-positive EGC patients. LVI-positive patients fulfilling the absolute endoscopic resection criteria did not have LNM and there was no significant difference in the overall (p = 0.928) and disease-specific survival (p = 0.821) between these patients and those with LVI-negative EGC. CONCLUSIONS: Additional surgery after endoscopic resection might be unnecessary in LVI-positive patients meeting the absolute criteria for endoscopic resection.

Online registry for nationwide database of Helicobacter pylori eradication in Korea: Correlation of antibiotic use density with eradication success.

BACKGROUND: The Helicobacter pylori eradication rate has decreased with increasing antibiotic resistance. We conducted a prospective, nationwide, multicenter registry study to monitor the real status of H. pylori eradication therapy and to investigate the association between eradication success and antibiotic use density in Korea. MATERIALS AND METHODS: We enrolled 9318 patients undergoing H. pylori eradication therapy from 37 hospitals through "on-line database registry" from October 2010 to July 2015. Demographic data, detection methods, treatment indications, regimens, durations, compliance, adverse events, and eradication results were collected. The use of all commercially available eradication antibiotics was analyzed through the Korean National Health Insurance data of the Health Insurance Review and Assessment Service. The defined daily dose of antibiotics was used to standardize drug use comparisons. RESULTS: Finally, 6738 patients were analyzed. The overall eradication rate of first-line therapy was 71.8%. The eradication success rates were 71.7%, 86.9%, and 74.0% for standard triple therapy for 7 days, quadruple therapy, and concomitant therapy, respectively. The eradication success rate in naive patients was higher than that in those who previously underwent H. pylori eradication. Eradication success was significantly associated with younger age, female sex, and high compliance. Regional differences in eradication rates were observed. The yearly use density of clarithromycin increased statistically in seven regions across the country from 2010 to 2015. The yearly use density of amoxicillin in the Gyeongsang and Chungcheong areas was significantly increased (P < .01), whereas that of other macrolides was significantly lower in the Gyeonggi area than in other areas (P = .01). The overall use of eradication antibiotics has increased while the eradication rate steadily decreased for 5 years. However, there was no significant correlation between antibiotic use density and eradication. CONCLUSION: There was no relationship between the eradication rate and antibiotic use density in Korea.

Physical Activity Protects Against the Risk of Erosive Esophagitis on the Basis of Body Mass Index.

GOAL: To determine whether physical activity lowers the risk for erosive esophagitis on the basis of body mass index (BMI). BACKGROUND: Although previous studies have shown that physical activity is closely associated with erosive esophagitis, these data may be confounded by obesity. STUDY: In this retrospective study, we included 182,409 patients who underwent an upper endoscopy and were diagnosed with erosive esophagitis. The impact of the amount and intensity of physical activity on the risk for erosive esophagitis was analyzed based on BMI groups. Subjects were classified into three BMI groups with equal numbers in each group. RESULTS: Overall, 10.3% (n=18,859) of patients were diagnosed with erosive esophagitis. After adjusting for confounding factors, a greater amount of exercise [lower tertile: odd ratio (OR), 0.86; 95% confidence interval (CI), 0.77-0.96; middle tertile: OR, 0.91; 95%, CI 0.84-1.00; upper tertile: OR, 0.79; 95% CI, 0.73-0.85) and increased exercise intensity (lower tertile, moderate: OR, 0.61; 95% CI, 0.52-0.71; vigorous: OR, 0.51; 95% CI, 0.44-0.58; middle tertile, moderate: OR, 0.62; 95% CI, 0.55-0.70; vigorous: OR, 0.58; 95% CI, 0.51-0.65; upper tertile, moderate: OR, 0.58; 95% CI, 0.53-0.65; vigorous: OR, 0.58; 95% CI, 0.53-0.64) was associated with a decreased risk for erosive esophagitis in all 3 BMI groups. In addition, we observed that increased physical activity intensity notably decreased the risk for erosive esophagitis in subjects performing lesser physical activity, but slightly decreased the risk for erosive esophagitis in subjects performing more physical activity. CONCLUSION: Physical activity is inversely associated with erosive esophagitis.

Endoscopic submucosal dissection for papillary adenocarcinoma of the stomach: low curative resection rate but favorable long-term outcomes after curative resection.

BACKGROUND: The previous studies demonstrated aggressive clinicopathologic features of papillary early gastric cancer (EGC). This raised concerns about the appropriateness of current Japanese guidelines that recommend the same endoscopic submucosal dissection (ESD) criteria for papillary EGC as for well-differentiated (WD) or moderately differentiated (MD) EGCs. METHODS: This study included 4140 patients who underwent ESD for differentiated-type EGC (87 papillary EGCs and 4259 WD or MD EGCs). The clinicopathologic characteristics and short- and long-term outcomes of ESD for papillary EGC were reviewed and compared with those for WD or MD EGC. RESULTS: Papillary EGCs were larger, and had higher lymphovascular and submucosal invasion rates than WD or MD EGCs. Lateral resection margin involvement and histological heterogeneity were found more frequently in papillary EGC than in WD or MD EGC. En bloc with R0 resection and curative resection rates of papillary EGC were 85.1 and 49.4%, respectively, and both were significantly lower than those of WD or MD EGC (93.0 and 82.2%). In mucosal cancers, curative resection rates of papillary EGC and WD or MD EGC were 72.5 and 93.7%, respectively. Among patients undergoing curative ESD for papillary EGC, no extra-gastric recurrences occurred during median 58 months of follow-up. Metachronous recurrence occurred in 5.2% of cases. CONCLUSIONS: Given the favorable long-term outcomes after curative resection, ESD might be indicated for papillary EGC according to the current Japanese guidelines. As papillary EGC has considerable lymphovascular and submucosal invasion rates, careful histological examination is required to accurately determine whether curative ESD is achieved.

Endoscopic vacuum therapy for postoperative esophageal leak.

BACKGROUND: Anastomotic leak is the most common and serious complication following esophagectomy. Endoscopic vacuum-assisted closure (EVAC) is a promising method for treating anastomotic leak. We aimed to evaluate the efficacy of EVAC and to identify factors associated with longer treatment duration for esophageal anastomotic leak following esophagectomy for cancer. METHODS: We retrospectively analyzed 20 esophageal cancer patients who had undergone EVAC for anastomotic leak after esophagectomy. The efficacy and success rates were evaluated and factors associated with longer treatment duration (≥ 21 days) were identified. RESULTS: All 20 patients were male. Of these, 10 (50.0%) received neoadjuvant treatment and 6 (30.0%) had one or more comorbidities. The median size of fistula opening was 1.75 cm. During a median of 14.5 days of EVAC treatment, a median of 5 interventions were performed. Treatment success was achieved in 19 patients (95.0%). Neoadjuvant treatment was significantly associated with longer EVAC treatment. There was a non-significant trend toward the need for longer treatment duration for a larger fistula opening size. CONCLUSIONS: EVAC treatment is a good non-surgical option for anastomotic leak following esophagectomy. Long duration of treatment is associated with neoadjuvant treatment and a large leakage opening.

Discovery and Validation of Salivary Extracellular RNA Biomarkers for Noninvasive Detection of Gastric Cancer.

BACKGROUND: Biomarkers are needed for noninvasive early detection of gastric cancer (GC). We investigated salivary extracellular RNA (exRNA) biomarkers as potential clinical evaluation tools for GC. METHODS: Unstimulated whole saliva samples were prospectively collected from 294 individuals (163 GC and 131 non-GC patients) who underwent endoscopic evaluation at the Samsung Medical Center in Korea. Salivary transcriptomes of 63 GC and 31 non-GC patients were profiled, and mRNA biomarker candidates were verified with reverse transcription quantitative real-time PCR (RT-qPCR). In parallel, microRNA (miRNA) biomarkers were profiled and verified with saliva samples from 10 GC and 10 non-GC patients. Candidate biomarkers were validated with RT-qPCR in an independent cohort of 100/100 saliva samples from GC and non-GC patients. Validated individual markers were configured into a best performance panel. RESULTS: We identified 30 mRNA and 15 miRNA candidates whose expression pattern associated with the presence of GC. Among them, 12 mRNA and 6 miRNA candidates were verified with the discovery cohort by RT-qPCR and further validated with the independent cohort (n = 200). The configured biomarker panel consisted of 3 mRNAs (SPINK7, PPL, and SEMA4B) and 2 miRNAs (MIR140-5p and MIR301a), which were all significantly down-regulated in the GC group, and yielded an area under the ROC curve (AUC) of 0.81 (95% CI, 0.72-0.89). When combined with demographic factors, the AUC of the biomarker panel reached 0.87 (95% CI, 0.80-0.93). CONCLUSIONS: We have discovered and validated a panel of salivary exRNA biomarkers with credible clinical performance for the detection of GC. Our study demonstrates the potential utility of salivary exRNA biomarkers in screening and risk assessment for GC.

Young Age and Risk of Lymph Node Metastasis in Differentiated Type Early Gastric Cancer.

BACKGROUND: Young patients with gastric cancer reportedly have a worse prognosis than older patients due to delayed diagnosis and more aggressive tumor behavior. However, it is unclear whether this applies to early gastric cancer (EGC), for which endoscopic resection is indicated. We investigated the association between age and lymph node metastasis (LNM). METHODS: We identified 4055 patients diagnosed with EGC of differentiated histology who underwent surgery. The association between age and LNM was examined using logistic regression for each T stage separately with adjustments for multiple covariates. We compared LNM rates for each of the Japanese Endoscopic Resection Guidelines criteria in younger (< 40 years) and older patients (40 years). RESULTS: The median number of lymph nodes examined was the same for T1a and T1b stages (n = 34). The median number of lymph nodes examined was not significantly different within T1a stage (P = 0.093), but within T1b stage, the number of lymph nodes examined was significantly different (P = 0.019). The highest number was between 50 and 59 years (median = 37), and the lowest number was in the 20 to 49 years and older than 70 age brackets (median = 34). LNM rate and age were not significantly associated within each stage (P values 0.269, 0.783 for T1a and T1b, respectively). Among patients fulfilling endoscopic resection criteria, the LNM rate in younger patients was lower than in older patients. CONCLUSIONS: In differentiated-type EGC, young age at diagnosis was not associated with LNM rate. Therefore, endoscopic resection criteria for early gastric cancer can be applied to younger patients.

Comparison of endoscopic submucosal dissection and surgery for superficial esophageal squamous cell carcinoma: a propensity score-matched analysis.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) has been widely accepted for treating superficial esophageal squamous cell carcinoma (SESCC). However, long-term outcomes of ESD and esophagectomy for SESCC have not been compared. We compared the clinical outcomes of ESD and esophagectomy in a matched cohort. METHODS: Patients who underwent ESD and esophagectomy for SESCC were included. We selected SESCCs without obvious submucosal invasion from the surgical database by reviewing endoscopic images. To minimize the effect of selection bias, propensity score matching was performed. Overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS), and metachronous RFS were compared between the 2 groups. Adverse event rates were also compared. RESULTS: In a matched cohort of 120 pairs, OS, DSS, and RFS were comparable between the 2 groups. The 5-year OS, DSS, and RFS rates were 93.9% versus 91.2%, 100% versus 97.4%, and 92.8% versus 95.3% for the ESD and esophagectomy groups, respectively. The metachronous RFS was worse in the ESD group than in the esophagectomy group (P = .004). The 5-year metachronous RFS rates were 90.3% versus 100% for the ESD and esophagectomy groups, respectively. The esophagectomy group showed a higher overall adverse event rate than the ESD group (55.5% vs 18.5%, P < .0001). In each subgroup of mucosal and submucosal cancer, OS, DSS, and RFS were also comparable between the 2 groups. CONCLUSIONS: ESD provides long-term outcomes comparable with esophagectomy in patients with SESCC without endoscopic evidence of obvious submucosal invasion. ESD should be considered as the first-line treatment for these patients.