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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.

Although colorectal cancer (CRC) is considered one of the most preventable cancers, no non-invasive, accurate diagnostic tool to screen CRC exists. We explored the potential of urine nuclear magnetic resonance (NMR) metabolomics as a diagnostic tool for early detection of CRC, focusing on advanced adenoma and stage 0 CRC. Urine metabolomics profiles from patients with colorectal neoplasia (CRN; 36 advanced adenomas and 56 CRCs at various stages, n = 92) and healthy controls (normal, n = 156) were analyzed by NMR spectroscopy. Healthy and CRN groups were statistically discriminated using orthogonal projections to latent structure discriminant analysis (OPLS-DA). The class prediction model was validated by three-fold cross-validation. The advanced adenoma and stage 0 CRC were grouped together as pre-invasive CRN. The OPLS-DA score plot showed statistically significant discrimination between pre-invasive CRN as well as advanced CRC and healthy controls with a Q2 value of 0.746. In the prediction validation study, the sensitivity and specificity for diagnosing pre-invasive CRN were 96.2% and 95%, respectively. The grades predicted by the OPLS-DA model showed that the areas under the curve were 0.823 for taurine, 0.783 for alanine, and 0.842 for 3-aminoisobutyrate. In multiple receiver operating characteristics curve analyses, taurine, alanine, and 3-aminoisobutyrate were good discriminators for CRC patients. NMR-based urine metabolomics profiles significantly and accurately discriminate patients with pre-invasive CRN as well as advanced CRC from healthy individuals. Urine-NMR metabolomics has potential as a screening tool for accurate diagnosis of pre-invasive CRN.

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.

Background Previous studies have suggested a link between Helicobacter pylori ( H. pylori ) infection and nonalcoholic fatty liver disease (NAFLD), yet large-scale longitudinal studies are lacking to elucidate this association. Methods A cohort study of 17,028 adults without NAFLD 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 NAFLD development. Fatty liver was diagnosed by ultrasonography. Results During the 83,130 person-years follow-up, participants with H. pylori infection had a higher rate of incident NAFLD than those who were uninfected. In a multivariable model adjusted for age, sex, body mass index, smoking status, alcohol intake, regular exercise, year of screening exam, and education level, the hazard ratio (HR) for NAFLD development in participants with H. pylori infection compared to those without infection was 1.21 [95% confidence interval (CI), 1.10–1.34]. The association persisted after further adjustment for metabolic variables, inflammatory marker, and liver enzymes. The association between H. pylori and NAFLD was still evident in an analysis using fatty liver index as a surrogate marker of NAFLD. In addition, the association between H. pylori infection and incident NAFLD did not differ across clinically relevant subgroups evaluated. Conclusions H. pylori infection was significantly associated with the development of NAFLD, independent of metabolic and inflammatory risk factors. H. pylori infection may play a pathophysiologic role in NAFLD development, indicating that H. pylori eradication might play a role in reducing the risk of NAFLD.

Despite the benefits from adjuvant chemotherapy or chemoradiotherapy, approximately one-third of stage II gastric cancer (GC) patients developed recurrences. The aim of this study was to develop and validate a prognostic algorithm for gastric cancer (GCPS) that can robustly identify high-risk group for recurrence among stage II patients. A multi-step gene expression profiling study was conducted. First, a microarray gene expression profiling of archived paraffin-embedded tumor blocks was used to identify candidate prognostic genes (N=432). Second, a focused gene expression assay including prognostic genes was used to develop a robust clinical assay (GCPS) in stage II patients from the same cohort (N=186). Third, a predefined cut off for the GCPS was validated using an independent stage II cohort (N=216). The GCPS was validated in another set with stage II GC who underwent surgery without adjuvant treatment (N=300). GCPS was developed by summing the product of Cox regression coefficients and normalized expression levels of 8 genes (LAMP5, CDC25B, CDK1, CLIP4, LTB4R2, MATN3, NOX4, TFDP1). A prospectively defined cut-point for GCPS classified 22.7% of validation cohort treated with chemoradiotherapy (N=216) as high-risk group with 5-year recurrence rate of 58.6% compared to 85.4% in the low risk group (hazard ratio for recurrence=3.16, p=0.00004). GCPS also identified high-risk group among stage II patients treated with surgery only (hazard ratio=1.77, p=0.0053).

Gastric cancer is the second most common cause of death from cancer in Asia. Although surgery is the standard treatment for this disease, early detection and treatment is the only way to reduce mortality. This Review summarises the epidemiology of gastric cancer, and the evidence for, and current practices of, screening in Asia. Few Asian countries have implemented a national screening programme for gastric cancer; most have adopted opportunistic screening of high-risk individuals only. Although screening by endoscopy seems to be the most accurate method for detection of gastric cancer, the availability of endoscopic instruments and expertise for mass screening remains questionable—even in developed countries such as Japan. Therefore, barium studies or serum-pepsinogen testing are sometimes used as the initial screening tool in some countries, and patients with abnormal results are screened by endoscopy. Despite the strong link between infection with Helicobacter pylori and gastric cancer, more data are needed to define the role of its eradication in the prevention of gastric cancer in Asia. At present, there is a paucity of quality data from Asia to lend support for screening for gastric cancer.

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 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.

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.