The majority of cancer patients respond poorly to either vaccine or checkpoint blockade, and even to the combination of both. They are often resistant to high doses of radiation therapy as well. We examined prognostic markers of immune cell infiltration in pancreatic cancer. Patients with low CD8+ T cell infiltration and high PD-L1 expression (CD8+ TloPD-L1hi) experienced poor outcomes. We developed a mouse tumor fragment model with a trackable model antigen (SIYRYYGL or SIY) to mimic CD8+ TloPD-L1hi cancers. Tumors arising from fragments contained few T cells, even after vaccination. Fragment tumors responded poorly to PD-L1 blockade, SIY vaccination or radiation individually. By contrast, local ionizing radiation coupled with vaccination increased CD8+ T cell infiltration that was associated with upregulation of CXCL10 and CCL5 chemokines in the tumor, but demonstrated modest inhibition of tumor growth. The addition of an anti-PD-L1 antibody enhanced the effector function of tumor-infiltrating T cells, leading to significantly improved tumor regression and increased survival compared to vaccination and radiation. These results indicate that sequential combination of radiation, vaccination and checkpoint blockade converts non-T cell-inflamed cancers to T cell-inflamed cancers, and mediates regression of established pancreatic tumors with an initial CD8+ TloPD-L1hi phenotype. This study has opened a new strategy for shifting “cold” to hot tumors that will respond to immunotherapy.

The suspension of elective operations in March 2020 to prepare for the COVID-19 surge posed significant challenges to resident education. To mitigate the potential negative effects of COVID-19 on surgical education, it is important to quantify how the pandemic influenced resident operative volume.OBJECTIVE To examine the association of the pandemic with general surgical residents' operative experience by postgraduate year (PGY) and case type and to evaluate if certain institutional characteristics were associated with a greater decline in surgical volume.

Background: Sarcopenia has been associated with increased adverse outcomes after major abdominal surgery. Sarcopenia defined as decreased muscle volume or increased fatty infiltration may be a proxy for frailty. In conjunction with other preoperative clinical risk factors, radiographic measures of sarcopenia using both muscle size and density may enhance prediction of outcomes after pancreaticoduodenectomy (PD) for malignancy. Methods: Preoperative computed tomography (CT) scans of patients undergoing PD for malignancy were analyzed from a prospective pancreatic surgery database. Sarcopenia was assessed both manually and with a semi-automated technique by measuring the total psoas area index (TPAI) and average Hounsfield units (HU) at the L3 lumbar level to estimate psoas muscle volume and density, respectively. Adjusting for known pre-operative risk factors, preoperative sarcopenia measurements were analyzed relative to perioperative outcomes. Results: Sarcopenia assessments of 116 subjects demonstrated good correlation between the semiautomated and the manual techniques (P<0.0001). Lower TPAI (OR 0.34, P=0.009) and HU (OR 0.84, P=0.002) measurements were predictive of discharge to skilled nursing facility (SNF), but not major complications, length of stay, readmissions or recurrence on univariate analysis. Lower TPAI was protective against the risk of organ/space surgical site infection (SSI) including pancreatic fistula (OR 3.12, P=0.019).On multivariate analysis, the semi-automated measurements of TPAI and HU remained as independent predictors of organ/space SSI including pancreatic fistula (OR 4.23, P=0.014) and discharge to SNF (OR 0.79, P=0.019) respectively. Conclusions: When combined with preoperative clinical assessments in patients with pancreatic malignancy, semi-automated sarcopenia metrics are a simple, reproducible method that may enhance prediction of outcomes after PD and help guide clinical management.

Objective: Single-center studies have demonstrated that resection of cavity shave margins (CSM) halves the rate of positive margins and re-excision in breast cancer patients undergoing partial mastectomy (PM). We sought to determine if these findings were externally generalizable across practice settings. Methods: In this multicenter randomized controlled trial occurring in 9 centers across the United States, stage 0–III breast cancer patients undergoing PM were randomly assigned to either have resection of CSM (“shave” group) or not (“no shave” group). Randomization occurred intraoperatively, after the surgeon had completed their standard PM. Primary outcome measures were positive margin and re-excision rates. Results: Between July 28, 2016 and April 13, 2018, 400 patients were enrolled in this trial. Four patients (2 in each arm) did not meet inclusion criteria after randomization, leaving 396 patients for analysis: 196 in the “shave” group and 200 to the “no shave” group. Median patient age was 65 years (range; 29–94). Groups were well matched at baseline for demographic and clinicopathologic factors. Prior to randomization, positive margin rates were similar in the “shave” and “no shave” groups (76/196 (38.8%) vs. 72/200 (36.0%), respectively, P = 0.604). After randomization, those in the “shave” group were significantly less likely than those in the “no shave” group to have positive margins (19/196 (9.7%) vs. 72/200 (36.0%), P < 0.001), and to require re-excision or mastectomy for margin clearance (17/196 (8.7%) vs. 47/200 (23.5%), P < 0.001). Conclusion: Resection of CSM significantly reduces positive margin and re-excision rates in patients undergoing PM.