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Background: Recent studies have indicated that the incidence of esophageal cancer has declined in the past decade in the U.S. However, trends in the incidence and survival have not been thoroughly examined. Methods: Data from 46 063 patients with esophageal cancer between 1973 and 2015 were collected from the Surveillance, Epidemiology, and End Results database. The trends in the age-adjusted incidence and survival were analyzed using joinpoint regression models. Results: The age-adjusted incidence of esophageal cancer increased from 5.55 to 7.44 per 100 000 person-years between 1973 and 2004. Later, it decreased at an annual percentage change of 1.23%. In the last 40 years, the strong male predominance increased slightly. Importantly, the percentage of patients with localized stage of squamous cell cancer decreased. It was observed that the incidence of esophageal squamous cell carcinoma declined since 1986, while the incidence of esophageal adenocarcinoma sharply increased since 1973 and surpassed the rate of squamous cell cancer, mainly due to the increase in the incidence among men. Consistently, the estimated 40-year limited-duration prevalence of esophageal adenocarcinoma was higher than that of esophageal squamous cell carcinoma. Additionally, we observed a modest but significant improvement in survival during the study period. Conclusion: The incidence of esophageal squamous cell carcinoma has decreased significantly over the past four decades in the U.S., while the incidence of adenocarcinoma has increased, particularly among men. Overall, the longterm survival of patients with esophageal cancer is poor but it has improved over the past decades, especially for the localized disease. Key pointsSignificant findings of the study The incidence of esophageal cancer has decreased at an annual percentage change of 1.23% since 2004. The incidence of esophageal adenocarcinoma has sharply increased since 1973 and surpassed the rate of squamous cell cancer, mainly due to the increase in the incidence among men. What this study adds There has been a shift in the prevalence of esophageal cancer histological subtypes over the past decades in the U.S. We found that the incidence of esophageal squamous cell carcinoma has continued to decrease, while the esophageal adenocarcinoma rate has continued to increase.

BackgroundMinimally invasive esophagectomy (MIE) was shown to be effective in reducing the morbidity and was adopted increasingly. The robot-assisted minimally invasive esophagectomy (RAMIE) remains in the initial stage of application. This study evaluated its safety and feasibility by comparing short-term outcomes of RAMIE and video-assisted minimally invasive esophagectomy (VAMIE).MethodsBetween March 2016 and December 2017, 115 consecutive patients underwent RAMIE or VAMIE at our institute. The baseline characteristics, pathological data and short-term outcomes of these two group patients were collected and compared. RAMIE patients were propensity score matched with VAMIE patients for a more accurate comparison.ResultsMatching based on propensity scores produced 27 patients in each group. After propensity score matching (PSM), the baseline characteristics between the two groups were comparable. The operation time in RAMIE group was significantly longer than that in VAMIE group (349 and 294 min, respectively; P < 0.001). The blood loss volume in RAMIE group was less than that in VAMIE group (119 and 158 ml, respectively), but with no statistically significant difference (P = 0.062). There was no significant difference between the two groups with respect to the mean number of dissected lymph nodes (20 and 19, respectively; P = 0.420), postoperative hospital stay (13.8 and 12.7 days, respectively; P = 0.548), the rate of overall complications (37.0 and 33.3%, respectively; P = 0.776) and the rates of detailed complications between the two groups.ConclusionsThe short-term outcomes of RAMIE is comparable to VAMIE, demonstrating safety and feasibility of RAMIE.

Oxaliplatin resistance undermines its curative effects on cancer and usually leads to local recurrence. The oxidative stress induced DNA damage repair response is an important mechanism for inducing oxaliplatin resistance by activating autophagy. ELISA is used to detect target genes expression. TMT-based quantitative proteomic analysis was used to investigate the potential mechanisms involved in NORAD interactions based on GO analysis. Transwell assays and apoptosis flow cytometry were used for biological function analysis. CCK-8 was used to calculate IC50 and resistance index (RI) values. Dual-luciferase reporter gene assay, RIP and ChIP assays, and RNA pull-down were used to detect the interaction. Autophagy flux was evaluated using electron microscope and western blotting. Oxidative stress was enhanced by oxaliplatin; and oxaliplatin resistance gastric cancer cell showed lower oxidative stress. TMT labeling showed that NORAD may regulate autophagy flux. NORAD was highly expressed in oxaliplatin-resistant tissues. In vitro experiments indicate that NORAD knockdown decreases the RI (Resistance Index). Oxaliplatin induces oxidative stress and upregulates the expression of NORAD. SGC-7901 shows enhanced oxidative stress than oxaliplatin-resistant cells (SGC-7901-R). NORAD, activated by H3K27ac and CREBBP, enhanced the autophagy flux in SGC-7901-R to suppress the oxidative stress. NORAD binds to miR-433-3p and thereby stabilize the ATG5- ATG12 complex. Our findings illustrate that NORAD, activated by the oxidative stress, can positively regulate ATG5 and ATG12 and enhance the autophagy flux by sponging miR-433-3p. NORAD may be a potential biomarker for predicting oxaliplatin resistance and mediating oxidative stress, and provides therapeutic targets for reversing oxaliplatin resistance.

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