Esophageal adenocarcinoma (EAC) ranks sixth in cancer mortality in the world and its incidence has risen dramatically in the western population over the last decades. Data presented herein strongly suggest that Notch signaling is critical for EAC and underlies resistance to chemotherapy. We present evidence that Notch signaling drives a cancer stem cell phenotype by regulating genes that establish stemness. Using patient derived xenograft models we demonstrate that inhibition of Notch by gamma-secretase inhibitors (GSI) is efficacious in downsizing tumor growth. Moreover, we demonstrate that Notch activity in a patient’s EUS-derived biopsy might predict outcome to chemotherapy. Therefore, this study provides a proof of concept that inhibition of Notch activity will have efficacy in treating EAC, offering a rationale to lay the foundation for a clinical trial to evaluate the efficacy of GSI in EAC treatment.
PURPOSE National guidelines recommend sentinel lymph node biopsy (SLNB) be offered to patients with > 10% likelihood of sentinel lymph node (SLN) positivity. On the other hand, guidelines do not recommend SLNB for patients with T1a tumors without high-risk features who have < 5% likelihood of a positive SLN. However, the decision to perform SLNB is less certain for patients with higher-risk T1 melanomas in which a positive node is expected 5%-10% of the time. We hypothesized that integrating clinicopathologic features with the 31-gene expression profile (31-GEP) score using advanced artificial intelligence techniques would provide more precise SLN risk prediction. METHODS An integrated 31-GEP (i31-GEP) neural network algorithm incorporating clinicopathologic features with the continuous 31-GEP score was developed using a previously reported patient cohort (n = 1,398) and validated using an independent cohort (n = 1,674). RESULTS Compared with other covariates in the i31-GEP, the continuous 31-GEP score had the largest likelihood ratio (G2 = 91.3, P < .001) for predicting SLN positivity. The i31-GEP demonstrated high concordance between predicted and observed SLN positivity rates (linear regression slope = 0.999). The i31-GEP increased the percentage of patients with T1-T4 tumors predicted to have < 5% SLN-positive likelihood from 8.5% to 27.7% with a negative predictive value of 98%. Importantly, for patients with T1 tumors originally classified with a likelihood of SLN positivity of 5%-10%, the i31-GEP reclassified 63% of cases as having < 5% or > 10% likelihood of positive SLN, for a more precise, personalized, and clinically actionable SLN-positive likelihood estimate. CONCLUSION These data suggest the i31-GEP could reduce the number of SLNBs performed by identifying patients with likelihood under the 5% threshold for performance of SLNB and improve the yield of positive SLNBs by identifying patients more likely to have a positive SLNB.
Postoperative mortality, morbidity, and length of stay in octogenarians are comparable to younger patients, while the overall survival is worse. With appropriate patient selection, good outcomes can be accomplished in octogenarians undergoing esophagectomy for cancer.
Anastomotic leak (AL) is one of the most serious complications after gastrointestinal surgery. All patients aged 16 years or older who underwent a surgery with single intestinal anastomosis at Morristown Medical Center from January 2006 to June 2008 were entered into a prospective database. To compare the rate of AL, patients were divided into the following surgery-related groups: 1) stapled versus hand-sewn, 2) small bowel versus large bowel, 3) right versus left colon, 4) emergent versus elective, 5) laparoscopic versus converted (laparoscopic to open) versus open, 6) inflammatory bowel disease versus non inflammatory bowel disease, and 7) diverticulitis versus nondiverticulitis. We also looked for surgical site infection, estimated intraoperative blood loss, blood transfusion, comorbidities, preoperative chemotherapy, radiation, and anticoagulation treatment. The overall rate of AL was 3.8 per cent. Mortality rate was higher among patients with ALs (13.3%) versus patients with no AL (1.7%). Open surgery had greater risk of AL than laparoscopic operations. Surgical site infection and intraoperative blood transfusions were also associated with significantly higher rates of AL. Operations involving the left colon had greater risk of AL when compared with those of the right colon, sigmoid, and rectum. Prior chemotherapy, anticoagulation, and intraoperative blood loss all increased the AL rates. In conclusion, we identified several significant risk factors for ALs. This knowledge should help us better understand and prevent this serious complication, which has significant morbidity and mortality rates.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.