Faigel, Douglas O.

ABSTRACT Telemedicine is a broad term that encompasses all aspects of utilizing information and communication technologies to provide health services at distant sites. The primary goal of telementoring is the education and training of gastrointestinal (GI) endoscopists particularly in areas where there is a shortage of endoscopy trainers. Telementoring in GI endoscopy can help to provide teaching and skills training both in simulator‐based learning, and endoscopic skills training in the context of patient care. This position statement aims to outline the role of telementoring within GI endoscopy, offering a general model for the introduction and evaluation of a telementoring program that incorporates both simulators for junior trainees and skills training for practicing endoscopists. We hope to highlight its utility and implementation in remote locations. WEO recognizes that telementoring is valuable to expand access to high‐quality endoscopy training especially in parts of the world where there is a shortage of endoscopy trainers and this document can serve as a guide in the planning and implementation of telementoring programs.

INTRODUCTION: To report the prevalence and outcomes of unselected pancreatic cancer (PC) patients with pathogenic/likely pathogenic germline variants (PGVs) detected using a universal testing approach. METHODS: We undertook a prospective, multisite study of germline sequencing using a >80 gene next-generation sequencing platform among 250 patients with PC (not selected for age or family history of cancer) between April 1, 2018, and March 31, 2020. Demographic, tumor characteristics, and clinical outcomes were compared between PGV carriers and noncarriers. RESULTS: Of 250 patients, the mean age was 65 years (SD 8.7), 56% was male, 83.6% was White, and 65.6% had advanced disease (stages III and IV). PGVs were found in 15.2% (N = 38) of patients, and 2 patients had more than 1 PGV. Variants of uncertain significance were found in 44.4% (N = 111). Family history of cancer (odds ratio: 2.36, 95% confidence interval: 1.14–5.19, P = 0.025) was associated with a higher risk of PGV. In a median follow-up of 16.5 months, the median overall survival was 16.8 months in PGV carriers compared with 16.5 months in noncarriers (hazard ratio: 0.51, 95% confidence interval: 0.25–1.01, P = 0.05). Higher levels of carbohydrate antigen 19-9 and advanced disease stages (III and IV) were associated with worse outcomes in both groups. Overall, 68% of PGV carriers had mutations in homologous recombination repair genes, including BRCA1 , BRCA2 , PALB2 , ATM , CHEK2 , NBN , and RAD51C . DISCUSSION: Universal multigene panel testing in PC reveals that 1 in 6 patients are carriers of PGV. Multigene germline testing should be used to aid in treatment selection, prognostication, and familial cancer counseling.

4118 Background: Germline variations in cancer susceptibility genes have important implications on treatment and family counseling in pancreatic cancer (PC). We report the prevalence and clinical outcomes of unselected PC patients with pathogenic germline variants (PGV) detected using a universal testing approach. Methods: We undertook a prospective multi-site study of germline sequencing using an >80 gene next-generation sequencing platform among 250 PC patients (not selected for age or family cancer history) between April 1, 2018 and March 31, 2020. Demographic, tumor characteristics and clinical outcomes were compared between PGV carriers and non-carriers. Results: Of 250 patients, the mean age was 65 years (SD 8.7), 56% were male, 83.6% were white and 65.6% had advanced disease (Stage III and IV). PGV were found in 15.2% (N=38) of patients, two patients had more than one PGV. Variants of uncertain significance were found in 44.4% (N=111). Family history of cancer (OR 2.36, 95% CI: 1.14-5.19, p=0.025) was associated with a higher risk of PGV. In a median follow up of 16.5 months, median overall survival was 16.8 months in PGV carriers compared with 16.5 months in non-carriers (HR 0.51, 95 %CI, 0.25-1.01, p=0.05). Higher levels of CA 19-9 and advanced stages (III and IV) were associated with worse outcomes in both groups. Overall, 68% of PGV carriers had mutations in homologous recombination repair (HRR) genes, including BRCA1, BRCA2, PALB2, ATM, CHEK2, NBN, RAD51C. In 65% of HRR gene carrier’s systemic therapy with platinum was used. Conclusions: Universal multi-gene panel testing in pancreatic cancer reveals that 1 in 6 patients are carriers of PGV and is associated with improved survival. Multi-gene germline testing should be used to aid in treatment selection, prognostication, and familial cancer counseling. Distribution of the 40 PGV by penetrance status.[Table: see text]

Saturated fat breaks down less during sudden illnesses, resulting in lower monomer concentrations, and reducing disease severity.

Abstract Background Pancreatic cystic lesions (PCLs) are increasingly found on cross-sectional imaging, with the majority having a low risk for malignancy. The added value of fine-needle aspiration (FNA) in risk stratification remains unclear. We evaluated the impact of three FNA needles on diagnostic accuracy, clinical management, and the ability to accrue fluid for tumor markers. Methods A multicenter prospective trial randomized 250 patients with PCLs ≥ 13 mm 2:1:1 to 19G Flex, 19G, and 22G needles with crossover for repeated FNA procedures. Diagnostic accuracy was established at 2-year follow-up, with the final diagnosis from surgical histopathology or consensus diagnosis by experts based sequentially on clinical presentation, imaging, and aspirate analysis in blinded review. Results Enrolled patients (36 % symptomatic) had PCLs in the head (44 %), body (28 %), and tail (26 %). Percentage of cyst volume aspirated was 78 % (72 % – 84 %) for 19G Flex, 74 % (64 % – 84 %) for 22G, and 73 % (63 % – 83 %) for 19G (P = 0.84). Successful FNA was significantly higher for 19G Flex (89 % [82 % – 94 %]) and 22G (82 % [70 % – 90 %]) compared with 19G (75 % [63 % – 85 %]) (P = 0.02). Repeated FNA was required more frequently in head/uncinate lesions than in body and tail (P < 0.01). Diagnostic accuracy of the cyst aspirate was 84 % (73 % – 91 %) against histopathology at 2-year follow-up (n = 79), and 77 % (70 % – 83 %) against consensus diagnosis among nonsurgical cases (n = 171). Related serious adverse events occurred in 1.2 % (0.2 % – 3.5 %) of patients. Conclusions Our study results demonstrate a statistically significant difference among the three needles in the overall success rate for aspiration, but not in the percentage of cyst volume aspirated. Flexible needles may be particularly valuable in sampling cystic PCLs in the pancreatic head/uncinate process.

Abstract Purpose: Quiescin Sulfhydryl Oxidase 1 (QSOX1) is an enzyme over-expressed by tumor cells. Our group and others have shown that QSOX1 is involved in invasion and metastasis. We previously reported that a small molecule, SBI-183, inhibited the enzymatic activity of QSOX1 and suppressed tumor cell invasion in vitro and metastasis of MDA-MB-231 breast tumor cells in vivo. In our current work we tested SPX-009, an analog of SBI-183 with increased potency, to suppress invasion and metastasis in vitro and in vivo. Methods: Commercially available analogs for SBI-183 were screened in a cell-free fluorescent screening assay for the ability to inhibit QSOX1. Analog compounds that inhibited QSOX1 in a concentration-dependent manner were then tested for the ability to inhibit growth and invasion of triple negative breast cancer (TNBC) cells (MDA-MB-231), sarcomatoid kidney cancer cells (RCJ-41T2) and pancreatic adenocarcinoma cells (MIAPaCa2). MTT assays were used to measure the effect of the compounds on tumor growth. 2D invasion assays and 3D tumor spheroid assays were employed to measure the effect of the analogs on invasion. One potent analog (SPX-009) was evaluated for the ability to suppress tumor growth and metastasis in mice bearing MDA-MB-231-luc breast cancer orthotopic xenografts. Results: Three of 53 analogs inhibited the enzymatic activity of QSOX1 at levels similar to the parent compound. However, one of those compounds, SPX-009, suppressed invasion of breast, kidney and pancreas tumor cells in 2D and 3D invasion assays at &gt;10-fold lower concentrations than the parent compound (SBI-183). In a non-metastatic xenograft of kidney cancer SBI-183 suppressed primary kidney tumor growth by 51%, but in a metastatic xenograft breast cancer model (MDA-MB-231-luc TNBC), SBI-183 reduced lung metastasis by 76% compared to control. Human-mouse xenograft studies are ongoing with the more potent analog (SPX-009) and will also be presented. Conclusions: Chemical inhibitors of QSOX1 have a minor effect on tumor cell viability, but a major effect on tumor cell invasion in vitro and metastasis in vivo. This finding suggests that combining a QSOX1 inhibitor with a cytotoxic agent might provide a means to inhibit metastasis of cells that are resistant to cytotoxic agents. Citation Format: Amber Fifield, Thai H. Ho, Douglas O. Faigel, Sergei Svarovsky, Eduard Sergienko, Thomas C. Chung, Douglas F. Lake. Chemical inhibitors of quiescin sulfhydryl oxidase (QSOX1) suppress tumor invasion and metastasis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5323.