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Few studies have compared the long-term outcomes of endoscopic resection and surgery. The aim of this study was to compare the long-term outcomes of endoscopic resection with those of surgery for early gastric cancer (EGC). We reviewed prospectively collected data of patients who had undergone endoscopic resection (1,290 patients) or surgery (1,273 patients) for EGC. To reduce the effect of selection bias, we performed a propensity score-matching analysis between the two groups. The primary outcome was overall survival (OS). The secondary outcomes were disease-specific survival, disease-free survival (DFS), recurrence-free survival (RFS), occurrence of metachronous gastric cancer, treatment-related complications, length of hospital stay, and 30-day outcomes. The study was designed as a non-inferiority study and tested in an intention-to-treat analysis. In a propensity-matched analysis of 611 pairs, the 10-year OS proportion was 96.7% in the endoscopic resection group and 94.9% in the surgery group (P=0.120) (risk difference -1.8%, 95% confidence interval (CI) -4.04-0.44, Pnon-inferiority=0.014), which met the non-inferiority criterion. In contrast, the 10-year RFS proportion was 93.5% in the endoscopic resection group and 98.2% in the surgery group (P<0.001) (risk difference 4.7%, 95% CI 2.50-6.97, Pnon-inferiority=0.820), which did not meet the non-inferiority criterion, mainly because of metachronous recurrence in the endoscopic resection group. The rate of early complications was higher in the endoscopic resection group than in the surgery group (9.0 vs. 6.6%, P=0.024), whereas the rate of late complications was higher in the surgery group than in the endoscopic resection group (0.5 vs. 2.9%, P<0.001). In the multiple Cox regression analysis, patient's age, the comorbidity index, the performance index, sex, tumor morphology, and depth of invasion were predictors of OS in patients with EGC. Endoscopic resection might not be inferior to surgery with respect to OS in patients with EGC lesions that meet the absolute or expanded criteria. However, DFS, RFS, and metachronous RFS might be lower after endoscopic resection than after surgery.

Intestinal-type gastric carcinoma exhibits a multistep carcinogenic sequence from adenoma to carcinoma with a gradual increase in genomic alterations. But the roles of microRNAs (miRNA) in this multistage cascade are not fully explored. To identify differentially expressed miRNA (DEM) during early gastric carcinogenesis, we performed miRNA microarray profiling with 24 gastric cancers and precursor lesions (7 early gastric cancer [EGC], 3 adenomas with high-grade dysplasia, 4 adenomas with low-grade dysplasia, and 10 adjacent normal tissues). Alterations in the expression of 132 miRNA were detected; these were categorized into three groups based on their expression patterns. Of these, 42 miRNAs were aberrantly expressed in EGC. Five miRNA (miR-26a, miR-375, miR-574-3p, miR-145, and miR-15b) showed decreased expression since adenoma. Expression of two miRNA, miR-200C and miR-29a, was down-regulated in EGCs compared to normal mucosa or adenomas. Six miRNA (miR-601, miR-107, miR-18a, miR-370, miR-300, and miR-96) showed increased expression in gastric cancer compared to normal or adenoma samples. Five representative miRNAs were further validated with RT-qPCR in independent 77 samples. Taken together, these results suggest that the dysregulated miRNA show alterations at the early stages of gastric tumorigenesis and may be used as a candidate biomarker.

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. 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. 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 ( , , and ) and 2 miRNAs ( and ), 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). 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.

BackgroundGastric 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.MethodsThe 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.ResultsA 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).ConclusionThis simple RSS could be useful for predicting the malignancy potential of gastric GISTs and may aid preoperative clinical decision making to ensure optimal treatment.

Esophageal endoscopic submucosal dissection (ESD) can be a curative treatment for superficial esophageal squamous cell carcinoma (SESCC). However, it is unclear whether the development of metachronous recurrence after ESD may be explained based on several risk factors. This study aimed to assess the incidence and the risk factors of metachronous recurrence of SESCC after ESD. This retrospective analysis was conducted at Samsung Medical Center, Seoul, Korea, from April 2007 to May 2018. Two hundred and fifty-three SESCC patients treated with ESD were followed using surveillance endoscopy after the procedure. Risk factors for metachronous esophageal SCC were analyzed using the Kaplan-Meier method and Cox's proportional hazards model. Metachronous esophageal SCCs were found in 21 (8.3%) of the 253 patients. Six patients (2.4%) with extraesophageal recurrence such as lymph node metastasis confirmed by imaging were excluded from patients with metachronous recurrence and data were censored from the recurrence date. Univariate analysis revealed that the presence of many (>10) irregularly shaped multiform Lugol-voiding lesions (LVLs) around the main lesion, margin of the main LVL, and tumor differentiation were risk factors for the development of metachronous cancer. Multivariate analysis also revealed that many (>10) LVLs (hazard ratio [HR], 6.32; 95% confidence interval [CI], 1.62-24.72; p = 0.047) and unclear or spiculated margin of the main LVL (HR, 6.51; 95% CI, 1.44-29.42; p = 0.029) were associated with the risk of metachronous recurrence. Metachronous esophageal SCC develops in patients treated with ESD for SESCC. A risk assessment is important for surveillance before and after ESD for SESCC. Number of LVLs and tumor edge type are associated with an increased risk of metachronous cancer in SESCC. Patients will benefit from careful endoscopic surveillance when endoscopists pay attention to these tumor characteristics.

BackgroundThe 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.MethodsThis 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.ResultsPapillary 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.ConclusionsGiven 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.

Background/Objectives: The curability of endoscopic submucosal dissection (ESD) for early gastric lymphoepithelioma-like carcinoma (LELC) remains unclear, as this rare histological subtype is not well represented in current guidelines. We aimed to evaluate the clinicopathological features and outcomes of early gastric LELC following ESD. Methods: We retrospectively compared 51 patients with early gastric LELC and 8243 patients with well- or moderately differentiated (WD or MD) tubular adenocarcinoma who underwent ESD. Results: LELC was more frequently located in the proximal stomach than WD/MD adenocarcinoma (52.9% vs. 10.3%). The deep submucosal invasion rate was significantly higher in LELC (77.3% vs. 9.5%), whereas the lymphatic invasion rate was comparable between the two groups (5.7% vs. 9.2%). No LELC cases were diagnosed preoperatively using forceps biopsy. Despite the comparable en bloc with R0 and complete resection rates, the curative resection rate of LELC was significantly lower than that of WD/MD adenocarcinoma, primarily due to deep submucosal invasion. Post-ESD bleeding was more frequent in LELC (11.3% vs. 2.7%). During a mean follow-up of 38.1 months, no extra-gastric recurrence was observed in patients who did not undergo additional surgery, and no lymph node metastasis was detected among the 23 patients who underwent gastrectomy. No gastric cancer-specific deaths occurred in the study population during follow-up. Conclusions: Considering these favorable long-term outcomes despite a low curative resection rate, early gastric LELC fulfilling the conventional curative criteria of current guidelines can be regarded as having been curatively treated by ESD, particularly in patients with high surgical morbidity.

Background The clinicopathological features of mixed-type (MT) early gastric cancer (EGC) according to Lauren’s classification remain uninvestigated. This study aimed to clarify the clinicopathological features of MT EGC, particularly in relation to lymph node metastasis (LNM) and long-term survival. Methods This study included 5309 patients who underwent gastrectomy for EGC. The clinicopathological features, LNM, and long-term outcomes of patients with MT carcinomas were compared with those of patients with intestinal-type (IT) and diffuse-type (DT) cancers. Furthermore, we evaluated the predictors of LNM in each Lauren classification subgroup. Results Patients with MT carcinomas were likelier to have larger tumors, submucosal invasion, lymphovascular invasion, and LNM than those with IT or DT carcinomas. Multivariate logistic regression analysis revealed that the Lauren classification was a significant predictor of LNM ( P  < 0.001). The significant predictors of LNM in MT carcinomas were female sex, greater tumor size, presence of submucosal invasion, and lymphovascular invasion. However, the overall survival of patients with MT carcinoma was not significantly different from that of patients with IT or DT carcinomas ( P  = 0.104). Conclusions The presence of MT EGC carries a higher risk of LNM compared with the presence of IT or DT carcinomas. Therefore, MT carcinomas should be managed with gastrectomy that includes lymph node dissection instead of endoscopic resection.

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.

BackgroundWhen 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.ObjectiveThe aim of this study was to compare the long-term oncologic safety between primary surgery and delayed surgery after ER.MethodsPatients 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).ResultsAfter 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.ConclusionsThe 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.