Background: Staging laparoscopy and peritoneal cytology can detect occult metastatic disease prior to treatment of gastric cancer. The yield of peritoneal staging in patients with early stage disease is lacking. We assess the yield of peritoneal staging in early stage gastric cancer and its impact on survival. Methods: Data were obtained from a prospective database of patients who underwent staging laparoscopy and peritoneal cytology for gastric cancer at our institution between July 1995 and July 2018. Clinical stage was determined by endoscopic ultrasound, and early stage was defined as cT1-2 and cN0. Rates of positive cytology and carcinomatosis at time of laparoscopy were obtained. Univariate analyses were used to compare groups, and Kaplan-Meier survival analyses were used to assess survival outcomes. Results: Eight hundred sixty-seven patients underwent staging laparoscopy and peritoneal cytology; 56 were defined as early stage. Age was 61 ± 12 years, 66.4% were male, and 62.3% were white. Of the patients with early stage disease, 17.9% had either gross carcinomatosis (10.7%) and/or positive peritoneal cytology (10.9%). All cases of peritoneal disease were in patients with cT2 disease. There were no differences in age, gender, or race based on peritoneal disease (all p > 0.05). The presence of carcinomatosis or positive cytology significantly affected overall survival (p < 0.001), regardless of clinical T or N stage. Conclusions: Peritoneal staging identifies metastatic disease in a significant number of patients with early stage disease. Given its poor prognosis and alternate therapy options, independent staging laparoscopy and peritoneal cytology should be considered in patients with early stage gastric adenocarcinoma.

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Background An opioid reduction education program to decrease discharge opioid prescriptions was initiated in our Department of Surgical Oncology. The study's aim was to measure the results and sustainability of these interventions 1 year later. Methods This prospective quality improvement project identified patients undergoing resection in five index tumor sites (peritoneal surface, sarcoma, stomach, pancreas, liver) at a high‐volume cancer center. Patients were grouped into pre‐education (PRE: July 2017–July 2018) and posteducation (POST: September 2018–July 2019) periods, before and after departmental education talks and videos in August 2018. Opioids were converted to oral morphine equivalents (OME) to compare the groups. Results Of 1168 evaluable patients (PRE 646, 55%; POST 522, 45%), the median last‐24‐h inpatient OME was 15 mg in PRE patients and 10 mg in POST patients (p < .001). Median discharge OME decreased from 200 mg in PRE to 100 mg in POST patients (p < .001). The frequency of patients with zero discharge opioids increased from 11% to 19% (p < .001). This discharge OME reduction amounted to 52,200 mg OME saved, or the equivalent of 6960 5‐mg oxycodone pills not disseminated. Conclusions A perioperative opioid reduction education program targeted to providers halved discharge OME, with sustained reductions 1 year later.

Objective: We compare neoadjuvant chemotherapy (CT) to neoadjuvant chemotherapy plus chemoradiation (CRT) for patients with gastric adenocarcinoma (GA). Summary of Background Data: The optimal neoadjuvant therapy regimen for resectable GA is not defined. Methods: Utilizing data from 2 high-volume cancer centers, we analyzed patients who underwent surgery for localized GA from 1/1/2000-12/31/2017. Standard CT regimens were used according to treatment period. We compared propensity matched cohorts based on age, sex, race, histology, and clinical stage. Results: Four-hundred five patients (age 62 ± 12 year, 58% male, 56% White) were analyzed. 231 (57%) received CRT and 174 (43%) received CT. Groups differed based on histopathologic characteristics including preoperative stage (p = 0.013). To control for these differences, propensity matched cohorts of 113 CT and 113 CRT patients were compared. CRT had similar frequencies of microscopically negative resections to CT (93% vs 91%, p = 0.81), but higher rates of complete pathologic response (15% vs 4%, p = 0.003) and lower pathologic stage (p = 0.002). Completion of intended perioperative therapy occurred in 63% of CT and 91% of CRT patients (p < 0.001). Median DFS was 45mo (95%CI: 20–70) in the CT group and 113mo (95%CI: 75–151) in the CRT group (p = 0.018). Median OS was 53mo (95%CI: 30–77) versus 120mo (95%CI: 101–138); p = 0.015. Conclusions: In this multi-institutional comparison of neoadjuvant CT and CRT for resectable GA, CRT is associated with higher rates of completed perioperative therapy, higher rates of complete pathologic response, lower pathologic stage, and improved survival. Level of Evidence: Level III

Rho GTPases mediate stromal-epithelial interactions that are important for mammary epithelial cell (MEC) morphogenesis. Increased extracellular matrix (ECM) deposition and reorganization affect MEC morphogenesis in a Rho GTPase-dependent manner. Although the effects of altered ECM on MEC morphogenesis have been described, how MECs regulate stromal deposition is not well understood. Previously, we showed that p190B RhoGAP overexpression disrupts mammary gland morphogenesis by inducing hyperbranching in association with stromal alterations. We therefore hypothesized that MEC overexpression of p190B regulates paracrine interactions to impact fibroblast activation. Using a combination of in vivo morphometric and immunohistochemical analyses and primary cell culture assays, we found that p190B overexpression in MECs activates fibroblasts leading to increased collagen, fibronectin, and laminin production and elevated expression of the collagen crosslinking enzyme lysyl oxidase. Phosphorylation of the TGF-β effector SMAD2 and expression of the TGF-β target gene αSma were increased in p190B-associated fibroblasts, suggesting that elevated TGF-β signaling promoted fibroblast activation. Mechanical tension and TGF-β cooperate to activate fibroblasts. Interestingly, active TGF-β was elevated in conditioned medium from p190B overexpressing MECs compared to control MECs, and p190B overexpressing MECs exhibited increased contractility in a collagen gel contraction assay. These data suggest that paracrine signaling from the p190B overexpressing MECs may activate TGF-β signaling in adjacent fibroblasts. In support of this, transfer of conditioned medium from p190B overexpressing MECs onto wildtype fibroblasts or co-culture of p190B overexpressing MECs with wildtype fibroblasts increased SMAD2 phosphorylation and mRNA expression of ECM genes in the fibroblasts when compared to fibroblasts treated with control CM or co-cultured with control MECs. The increased ECM gene expression and SMAD2 phosphorylation were blocked by treatment with a TGF-β receptor inhibitor. Taken together, these data suggest that p190B overexpression in the mammary epithelium induces fibroblast activation via elevated TGF-β paracrine signaling.

An oligometastatic cancer state was first postulated in the 1990s by Hellman and Weichselbaum and described limited metastatic spread to a single or few sites of disease. It was hypothesized that this metastatic entity falls along a continuum of the natural history of cancer progression from a localized primary tumor to widespread metastases. Support for oligometastatic non-small cell lung cancer (NSCLC) has since been provided by multiple retrospective studies and then prospective randomized trials demonstrating better survival in this patient population after aggressive consolidative treatment. However, the lack of a universal definition of oligometastatic NSCLC has hindered a comparison between different studies and prevented well-defined recommendations for local consolidative treatment in this patient population. Attempts have been made to establish a common definition for use in clinical management and for the identification of inclusion criteria for future trials. In this review, we seek to summarize the current definitions of oligometastatic NSCLC based on recent expert consensus statements, previous randomized trials, and current treatment guidelines and to highlight the continued variability in current practice.

Background and Objectives We sought to evaluate the impact of lymphovascular invasion (LVI) and perineural invasion (PNI) on survival outcomes in gastric cancer patients treated with preoperative therapy. Methods Patients with gastric cancer treated with preoperative therapy and potentially curative resection were stratified according to the presence of LVI, PNI, or both. Kaplan–Meier and Cox regression analyses were used to evaluate the impact on overall survival (OS) and disease‐free survival (DFS). Results The study included 281 patients, of whom 93 (33%) had LVI, 69 (25%) had PNI, 51 (18%) had both LVI and PNI, and 170 (61%) had neither. LVI and PNI were each associated with higher ypT and ypN categories and more positive lymph nodes (all p < .001), associations that were emphasized with both factors present. On multivariable analyses, ypN (p < .001) and concurrent LVI/PNI (hazard ratio [HR]: 2.62; 95% confidence interval [CI]: 1.55–4.45; p = .001) were predictive of OS and DFS (ypN: p < .001; both LVI/PNI: HR: 2.27; 95% CI: 1.34–3.82; p = .002). Conclusions Gastric cancer patients with concurrent LVI and PNI after preoperative therapy have more advanced disease and worse survival outcomes than patients with neither or only one of these factors.