No abstract

Purpose: Aggressive variant prostate cancer (AVPC) represents a clinical subset distinguished by therapy resistance and poor prognosis, linked to combined losses of the tumor suppressor genes (TSG) PTEN, RB1, and TP53. Circulating tumor cells (CTC) provide a minimally invasive opportunity for identification and molecular characterization of AVPC. We aimed to evaluate the incidence and clinical significance of compound (2þ)TSG losses and genomic instability in prostate cancer CTC, and to expand the set genomic biomarkers relevant to AVPC.Experimental Design: Genomic analysis of chromosomal copy-number alterations (CNA) at single-cell resolution was performed in CTC from patients with and without AVPC before initiating chemotherapy with cabazitaxel or cabazitaxel and carboplatin. We evaluated associations between single-CTC genomics and clinical features, progression-free survival, and overall survival.Results: A total of 257 individual CTC were sequenced from 47 patients (1-22 CTC/patient). Twenty patients (42.6%) had concurrent 2þTSG losses in at least one CTC in association with poor survival and increased genomic instability, inferred by high large-scale transitions scores. Higher LST in CTC were independent of CTC enumerated, clinically more indicative of aggressive behavior than co-occurring TSG losses, and molecularly associated with gains in chromosomal regions including PTK2, Myc, and NCOA2; increased androgen receptor expression; and BRCA2 loss. In 57 patients with matched cell-free tumor DNA data, CTC were more frequently detectable and evaluable for CNA analysis (in 73.7% vs. 42.1%, respectively).Conclusions: Our findings suggest that genomic instability in CTC is a hallmark of advanced prostate cancer aggressiveness, and support single-CTC sequencing as a compelling tool to noninvasively characterize cancer heterogeneity.

Pseudomyogenic hemangioendothelioma (PMH) is a recently described, indolent vascular tumor that usually presents in the distal extremities. PMH typically has a multi-focal presentation and can involve several tissue planes including the dermis, subcutis, muscle, and bone. This soft tissue tumor predominantly affects men between 20 and 50 years of age. PMH tumors typically are resected but frequently recur locally; thus, more efficacious treatment options are needed. Herein, we report two cases of patients with PMH who were treated with systemic therapy. To the best of our knowledge, our report is the first to describe a response of PMH either to gemcitabine/taxane cytotoxic chemotherapy or to a mammalian target of rapamycin inhibitor. In the first case, a 45-year-old man with PMH of the right ilium was treated with gemcitabine plus docetaxel. Although chemotherapy was ultimately halted owing to gemcitabine-induced pulmonary toxicity, positron emission tomography-computer tomography scans taken after three cycles of gemcitabine plus docetaxel illustrated a noticeable response to the regimen. In the second case, a 22-year-old man with PMH of the right distal femur and metastases in the left ilium showed no response to gemcitabine plus docetaxel therapy, but underwent surgical resection after cisplatin and doxorubicin resulted in stable disease. DNA sequencing of his tumor revealed the presence of a tuberous sclerosis 1 (TSC1) mutation, so daily everolimus, which inhibits mammalian target of rapamycin, was started. Two months after beginning everolimus, the patient underwent magnetic resonance imaging of the pelvis, which revealed mild shrinkage of PMH metastases in the left iliac bone. Despite the apparent heterogeneity of response to gemcitabine/taxane chemotherapy in our two patients, these two cases indicate that gemcitabine/taxane and mammalian target of rapamycin inhibitor may serve as systemic treatment options for PMH and warrant further investigation.

Introduction:Shift Work Disorder (SWD) is a sleep disorder characterized by sleepiness and insomnia, which can be attributed to the person's work schedule. Awareness of the mechanisms behind shift work related health problems could be essential to schedule the shift work, employment routines, clinical treatment, and selection of employees.Objective:To assess the prevalence of SWD and to identify related health problems among nurses in a tertiary care hospital in Bangalore.Materials and Methods:We conducted a descriptive cross-sectional study in a tertiary care hospital in Bangalore between May and September 2014. Based on simple random sampling, 130 nurses were selected for the study. After obtaining written informed consent from the participants, structured interview schedule using Standard Shift Work Index and Bergen Shift Work Sleep Questionnaire (BSWSQ) was administered.Results:The mean age of the 130 nurses was 27.4 ± 2.64 years. The prevalence of SWD was found to be 43.07%. Headache, back pain, gastritis, and menstrual disorders were the most common complaints, which are found in 78 (60.0%), 75 (57.6%), 42 (32.3%), and 39 (30.0%) cases, respectively. Anxiety and depression was found in 23 (17.6%) and 31 (23.8%) individuals, respectively. We also found a significant association of SWD with increasing age, more number of nights worked in a year, and longer duration of working hours. According to the BSWSQ, 70 (53.8%) nurses were found to have sleep problems.Conclusion:A high prevalence of SWD symptoms calls for a focus on the antecedents of work related sleep problems and appropriate intervention, such as behavioral changes, clockwise rotating shifts, and treatment.