Exposure to toxicants leads to cumulative molecular changes that overtime increase a subject’s risk of developing urothelial carcinoma (UC). To assess the impact of arsenic exposure at a time progressive manner, we developed and characterized a cell culture model and tested a panel of miRNAs in urine samples from arsenic exposed subjects, UC patients and controls. To prepare an in vitro model, we chronically exposed an immortalized normal human bladder cell line (HUC1) to arsenic. Growth of the HUC1 cells was increased in a time dependent manner after arsenic treatment and cellular morphology was changed. In soft agar assay, colonies were observed only in arsenic treated cells and the number of colonies gradually increased with longer periods of treatment. Similarly, invaded cells in invasion assay were observed only in arsenic treated cells. Withdrawal of arsenic treatment for 2.5 months did not reverse the tumorigenic properties of arsenic treated cells. Western blot analysis demonstrated decreased PTEN and increased AKT and mTOR in arsenic treated HUC1 cells. Levels of miR-200a, miR-200b, and miR-200c were down-regulated in arsenic exposed HUC1 cells by quantitative RT-PCR. Furthermore, in human urine, miR-200c and miR-205 were inversely associated with arsenic exposure (P=0.005 and 0.009, respectively). Expression of miR-205 discriminated cancer cases from controls with high sensitivity and specificity (AUC=0.845). Our study suggests that exposure to arsenic rapidly induces a multifaceted dedifferentiation program and miR-205 has potential to be used as a marker of arsenic exposure as well as a maker of early UC detection.

Key Points Question Is the timing of adjuvant therapy in resected pancreatic cancer associated with better survival? Findings This cohort study of 7548 patients with stage I to II pancreatic cancer in the National Cancer Database suggested improved survival when adjuvant therapy was initiated 28 to 59 days after surgery. Patients who recovered slowly from surgery still benefited from delayed adjuvant therapy initiated more than 12 weeks after the procedure compared with patients who received surgery alone. Meaning Shared decision-making between clinicians and patients is needed to individualize when to initiate adjuvant therapy based on patients’ postoperative recovery.

Chest wall boost (CWB) is a common practice in postmastectomy radiation therapy (PMRT) in the United States, where more than 65% of women receiving PMRT receive CWB. We studied 746 patients who received PMRT and reconstruction; 379 (51%) of them received Purpose: Giving an additional radiation dose to the incision or chest wall has been a practice, but it has never been studied in a randomized setting, and it might lead to inferior cosmetic outcomes. This study aims to evaluate whether delivery of a chest wall boost (CWB) to the mastectomy scar or chest wall is independently associated with reconstruction complications and to assess its disease control efficacy in the setting of breast reconstruction. Methods and Materials: We conducted a retrospective chart review of 746 patients with breast cancer who underwent mastectomy, breast reconstruction, and PMRT; all underwent treatment at our institution during 1997 to 2016. Various reconstruction techniques were used among this cohort including autologous reconstruction, singlestage direct-to-implant reconstruction, and 2-stage tissue expander implant. Cohorts were divided by administration of CWB. The primary objective was comparing the