Effect of Neoadjuvant Chemotherapy on Tumor-Infiltrating Lymphocytes in Resectable Gastric Cancer: Analysis from a Western Academic Center.

Tumor-infiltrating lymphocytes (TILs) are an emerging biomarker predictive of response to immunotherapy across a spectrum of solid organ malignancies. The characterization of TILs in gastric cancer (GC) treated with contemporary, multiagent neoadjuvant chemotherapy (NAC) is understudied. In this retrospective investigation, we analyzed the degree of infiltration, phenotype, and spatial distribution of TILs via immunohistochemistry within resected GC specimens treated with or without NAC at a Western center. We hypothesized that NAC executes immunostimulatory roles, as evidenced by an increased number of anti-tumor TILs in the tumor microenvironment. We found significantly elevated levels of conventional and memory CD8+ T cells, as well as total TILs (CD4+, CD8+, Treg, B cells), within chemotherapy-treated tumors compared with chemotherapy-naïve specimens. We also revealed important associations between survival and pathologic responses with enhanced TIL infiltration. Taken together, our findings advocate for an immunostimulatory role of chemotherapy and underscore the potential synergistic effect of combining chemotherapy with immunotherapy in resectable gastric cancer.

Immune Landscape of Epstein-Barr Virus-Associated Gastric Cancer: Analysis From a Western Academic Institution.

INTRODUCTION: Epstein-Barr virus-associated gastric cancer (EBVaGC) may be a meaningful biomarker for potential benefit from immunotherapy. Further investigation is needed to characterize the immune landscape of EBVaGC. We assessed our institutional frequency of surgically treated EBVaGC and analyzed the immunologic biomarker profile and tumor-infiltrating lymphocyte (TIL) phenotypes of a series of EBVaGC compared to non-EBVaGC cases. METHODS: Available tissue samples from all patients with biopsy-confirmed gastric adenocarcinoma who underwent resection with curative intent from 2012 to 2020 at our institution were collected. In situ hybridization was used to assess EBV status; multiplex immunohistochemistry was performed to assess mismatch repair status, Programmed Death-Ligand 1 (PD-L1) expression, and phenotypic characterization of TILs. RESULTS: Sixty-eight samples were included in this study. EBVaGC was present in 3/68 (4%) patients. Among all patients, 27/68 (40%) had positive PD-L1 expression; two of three (67%) EBVaGC patients exhibited positive PD-L1 expression. Compared to non-EBVaGC, EBV-positive tumors showed 5-fold to 10-fold higher density of TILs in both tumor and stroma and substantially elevated CD8+ T cell to Tregulatory cell ratio. The memory subtypes of CD8+ and CD4+ T cells were upregulated in EBVaGC tumors and stromal tissue compared to non-EBVaGC. CONCLUSIONS: The incidence of surgically resected EBVaGC at our center was 4%. EBVaGC tumors harbor elevated levels of TILs, including memory subtypes, within both tumor and tumor-related stroma. Robust TIL presence and upregulated PD-L1 positivity in EBVaGC may portend promising responses to immunotherapy agents. Further investigation into routine EBV testing and TIL phenotype of patients with gastric cancer to predict response to immunotherapy may be warranted.

The Effect of Laparoscopic Gastric Ischemic Preconditioning Prior to Esophagectomy on Anastomotic Stricture Rate and Comparison with Esophagectomy-Alone Controls.

BACKGROUND: Benign anastomotic stricture is a recognized complication following esophagectomy. Laparoscopic gastric ischemic preconditioning (LGIP) prior to esophagectomy has been associated with decreased anastomotic leak rates; however, its effect on stricture and the need for subsequent endoscopic intervention is not well studied. METHODS: This was a case-control study at an academic medical center using consecutive patients undergoing oncologic esophagectomies (July 2012-July 2022). Our institution initiated an LGIP protocol on 1 January 2021. The primary outcome was the occurrence of stricture within 1 year of esophagectomy, while secondary outcomes were stricture severity and frequency of interventions within the 6 months following stricture. Bivariable comparisons were performed using Chi-square, Fisher's exact, or Mann-Whitney U tests. Multivariable regression controlling for confounders was performed to generate risk-adjust odds ratios and to identify the independent effect of LGIP. RESULTS: Of 253 esophagectomies, 42 (16.6%) underwent LGIP prior to esophagectomy. There were 45 (17.7%) anastomotic strictures requiring endoscopic intervention, including three patients who underwent LGIP and 42 who did not. Median time to stricture was 144 days. Those who underwent LGIP were significantly less likely to develop anastomotic stricture (7.1% vs. 19.9%; p = 0.048). After controlling for confounders, this difference was no longer significant (odds ratio 0.46, 95% confidence interval 0.14-1.82; p = 0.29). Of those who developed stricture, there was a trend toward less severe strictures and decreased need for endoscopic dilation in the LGIP group (all p < 0.20). CONCLUSION: LGIP may reduce the rate and severity of symptomatic anastomotic stricture following esophagectomy. A multi-institutional trial evaluating the effect of LGIP on stricture and other anastomotic complications is warranted.

Hazards of surgical smoke from electrocautery: A critical review of the data.

INTRODUCTION: Concerns have been voiced regarding the possibility of health risks to the operating room personnel from exposure to surgical smoke generated from electrocautery. METHODS: Ovid Medline was queried using search terms "surgical smoke", "electrosurgery," "smoke evacuator". The NIOSH Health Hazard Evaluations Database was searched using terms, "hospital", "operating room", "Ames", "mutagen", and "salmonella". RESULTS: Levels of pollutants in the breathable airspace within the operating room have been repeatedly shown to be very low. Absolute counts of particulate matter in the operating room are low when compared to other environments. The possibility for virus transmission with electrocautery in the operating room is unknown. CONCLUSIONS: The risks related to the exposure to electrocautery surgical smoke have been overstated. Rigid mandates requiring smoke evacuators in all situations are not justified at this time.