Citations

Abstract Objective: More than 5,000 premenopausal women are diagnosed with lung cancer annually in the United States. Limited data exist regarding the risk of treatment-related amenorrhea, a surrogate for infertility and early menopause, after systemic therapies for lung cancer. Methods: Premenopausal women diagnosed with lung cancer under age 50 were surveyed at diagnosis and annually thereafter about their menstrual status as a part of the Mayo Clinic Epidemiology and Genetics of Lung Cancer Research Program. Types of lung cancer-directed treatments were recorded, and frequencies of self-reported menopause at each survey were calculated. Results: A cohort of 182 premenopausal women were included in this study, with average age at lung cancer diagnosis 43 years (SD 6). Among the 85 patients who received chemotherapy, 64% self-reported that they had become menopausal within a year of diagnosis. Platinum salts were universally included in these chemotherapy regimens, and the majority of these women also received taxanes within 1 year of diagnosis. Only 15% of the 94 patients who did not receive systemic therapy within 1 year of diagnosis experienced self-reported menopause. Three patients received targeted therapy alone, two of whom remained premenopausal at the final qualifying survey, completed a median of 3 years after diagnosis. Conclusions: Chemotherapy for lung cancer patients appears to increase risk of early loss of menses in survivors.

Abstract Objective Genome-wide association studies (GWAS) identify associations of individual SNPs with cancer risk but usually only explain a fraction of the inherited variability. Pathway analysis of genetic variants has been shown for many disorders to be a powerful tool in discovering novel networks of susceptibility genes. Design We have conducted a large agnostic pathway-based meta-analysis of GWAS data using the summary-based adaptive rank truncated product (sARTP) method to identify novel gene sets and pathways associated with pancreatic ductal adenocarcinoma (PDA) in 9,040 cases and 12,495 controls. We performed expression quantitative trait loci (eQTL) analysis and functional annotation of the top SNPs in genes identified in PDA-associated gene sets and pathways. Results We identified 14 gene sets and pathways associated with PDA at FDR < 0.05. Five of the strongest signals (P-value ≤ 1.3x10-5 Bonferroni corrected) were in genes from KEGG maturity onset diabetes of the young, Reactome regulation of beta cell development, Biocarta role of epidermal growth factor (EGF) receptor transactivation by G-protein-coupled receptors in cardiac hypertrophy pathway, Nikolsky breast cancer chr17q11-q21 amplicon gene set, and Pujana ATM Pearson correlation coefficient (PCC) network gene set. We identified and validated rs876493 and three correlated SNPs (PGAP3) and rs3124737 (CASP7) as eQTLs in two normal derived pancreas tissue datasets. Conclusion Our agnostic gene set and pathway analysis integrated with functional annotation and eQTL analysis provides novel insight into genes and pathways that may be biologically relevant for risk of PDA. Citation Format: Naomi Walsh, Han Zhang, Paula L. Hyland, Qi Yang, Evelina Mocci, Mingfeng Zhang, Erica J. Childs, Zhaoming Wang, Stephen Chanock, Patricia Hartge, Robert Hoover, Peter Kraft, Donghui Li, Eric J. Jacobs, Gloria M. Petersen, Brian M. Wolpin, Harvey A. Risch, Laufey T. Amundadottir, Kai Yu, Alison P. Klein, Rachael Z. Stolzenberg-Solomon. Large pathway and gene set analysis of GWAS data identifies novel associations for pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 242.

AbstractBackgroundSeveral factors affect the level of difficulty of laparoscopic distal pancreatectomy (LDP). The purpose of this study was to develop a difficulty scoring (DS) system to quantify the degree of difficulty in LDP.MethodsWe collected clinical data for 80 patients who underwent LDP. A 10‐level difficulty index was developed and subcategorized into a three‐level difficulty index; 1–3 as low, 4–6 as intermediate, and 7–10 as high index. The automatic linear modeling (LINEAR) statistical tool was used to identify factors that significantly increase level of difficulty in LDP.ResultsThe operator's 10‐level DS concordance between the 10‐level DS by the reviewers, LINEAR index DS, and clinical index DS systems were analyzed, and the weighted Cohen's kappa statistic were at 0.869, 0.729, and 0.648, respectively, showing good to excellent inter‐rater agreement. We identified five factors significantly affecting level of difficulty in LDP; type of operation, resection line, proximity of tumor to major vessel, tumor extension to peripancreatic tissue, and left‐sided portal hypertension/splenomegaly.ConclusionsThis novel DS for LDP adequately quantified the degree of difficulty, and can be useful for selecting patients for LDP, in conjunction with fitness for surgery and prognosis.

AbstractBackgroundMinimally invasive distal pancreatectomy (MIDP) has gained in popularity recently. However, there is no consensus on whether to preserve the spleen or not. In this study, we compared MIDP outcomes between spleen‐preserving distal pancreatectomy (SPDP) and distal pancreatectomy with splenectomy (DPS); as well as outcomes between splenic vessel preservation (SVP) and Warshaw's technique (WT).MethodsA systematic search of PubMed (MEDLINE) and Cochrane Library was conducted and the reference lists of review articles were hand‐searched.ResultsFifteen relevant studies with 769 patients were selected for meta‐analyses of DPS and SPDP, while another 15 studies with 841 patients were used for the analysis between SVP and WT. Compared with the DPS group, SPDP patients had significantly lower incidences of infectious complications (P = 0.006) and pancreatic fistula (P = 0.002), shorter operative time (P < 0.001), and less blood loss (P = 0.01). Compared with WT, SVP patients had significantly lower incidences of splenic infarction (P < 0.001) and secondary splenectomy (P = 0.003). Subanalysis for laparoscopic surgery alone had similar results.ConclusionsBased on this study, SPDP has significantly superior outcomes compared to DPS. When a spleen is preserved, SVP has better outcomes over WT for reducing splenic complications.