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Anderson K.S.,Arizona State University | Cunliffe H.E.,University of Otago | Klassen C.L.,Section of Surgical Oncology | Dueck A.C.,Section of Biostatistics | And 2 more authors.
Oncotarget | Year: 2015

We used DNA content flow cytometry followed by oligonucleotide array based comparative genomic hybridization to survey the genomes of 326 tumors, including 41 untreated surgically resected triple negative breast cancers (TNBC). A high level (log2ratio ≥1) 9p24 amplicon was found in TNBC (12/41), glioblastomas (2/44), and colon carcinomas (2/68). The shortest region of overlap for the amplicon targets 9p24.1 and includes the loci for PD-L1, PD-L2, and JAK2 (PDJ amplicon). In contrast this amplicon was absent in ER+ (0/8) and HER2+ (0/15) breast tumors, and in pancreatic ductal adenocarcinomas (0/150). The PDJ amplicon in TNBCs was correlated with clinical outcomes in group comparisons by two-sample t-tests for continuous variables and chi-squared tests for categorical variables. TNBC patients with the PDJ amplicon had a worse outcome with worse disease-free and overall survival. Quantitative RT-PCR confirmed that the PDJ amplicon in TNBC is associated with elevated expression of JAK2 and of the PD-1 ligands. These initial findings demonstrate that the PDJ amplicon is enriched in TNBC, targets signaling pathways that activate the PD-1 mediated immune checkpoint, and identifies patients with a poor prognosis. Source

Moreno-Aspitia A.,Mayo Medical School | Dueck A.C.,Section of Biostatistics | Perez E.A.,Mayo Medical School
Cancer | Year: 2013

BACKGROUND Data suggest that weight, and specifically body mass index (BMI), plays a role in breast cancer development and outcome. The authors hypothesized that there would be a correlation between BMI and clinical outcome in patients with early stage, human epidermal receptor 2 (HER2)-positive breast cancer enrolled in the N9831 adjuvant trial. METHODS Patients were grouped according to baseline BMI as follows: normal (BMI <25 kg/m2), overweight (BMI ≥25 kg/m2 and <30 kg/m2), and obese (BMI ≥30 kg/m2). Disease-free survival (DFS) was estimated using the Kaplan-Meier method. Comparisons between treatment arms A, B, and C (chemotherapy with or without trastuzumab) were performed using a stratified Cox proportional hazards model. RESULTS Analysis was completed on 3017 eligible patients. Obese patients were more likely to be older and postmenopausal (P <.0001 for both), to have larger tumors (P =.002), and to have positive lymph nodes (P =.004). In the pooled analysis cohort, differences in DFS among the BMI groups were statistically significant (5-year DFS rate: 82.5%, 78.6%, and 78.5% for normal weight, overweight, and obese women, respectively; log-rank P =.02). The adjusted hazard ratio comparing the DFS of overweight women with the DFS of normal women was 1.30 (95% confidence interval, 1.06-1.61); and, comparing the DFS of obese women with the DFS normal women, the adjusted hazard ratio was 1.31 (95% confidence interval, 1.07-1.59). There were no statistically significant differences in DFS by weight group for women within any trial arm. CONCLUSIONS Patients with early stage, HER2-positive breast cancer and normal BMI had a better 5-year DFS compared with overweight and obese women. The current results indicated that adjuvant trastuzumab improves clinical outcome regardless of BMI. © 2013 American Cancer Society. Source

Kennedy G.D.,Section of Colon and Rectal Surgery | Rajamanickam V.,Section of Biostatistics | Oconnor E.S.,Section of Colon and Rectal Surgery | Loconte N.K.,University of Wisconsin - Madison | And 3 more authors.
Annals of Surgery | Year: 2011

Objective: We have undertaken the current study to evaluate factors that correlate with postoperative complications in older patients undergoing surgery for colon cancer. Patients and Methods: The database of the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) from years 2005 to 2008 was accessed. Patients age 65 and older were included according to Current Procedural Terminology and International Classification of Disease-9 codes. Preoperative and operative variables were examined and postoperative complications assessed using a combination of univariate and multivariate statistical models. Propensity score matching was used to control for nonrandomization of the database. Results:: We found that patients undergoing laparoscopic (n = 2113) and open (n = 3801) surgery for the diagnosis of colon cancer were similar in age and gender. However, patients undergoing laparoscopic surgery were generally at lower risk for developing postoperative complications (16.1% vs. 25.4%, P < 0.005). Statistical models controlling for preoperative and operative variables demonstrated patients with elevated body mass index (odds ratio [OR] = 1.26), a history of chronic obstructive pulmonary disease (OR = 1.63), over age 85 (OR = 1.35), a surgery lasting longer than 4 hours (OR = 1.48), or having undergone an open operation (OR = 1.53) to have increased risk for developing postoperative complications. Propensity score match analysis confirmed these results. Conclusions: Identification of preoperative factors that predispose patients to postoperative complications could allow for the institution of protocols that may decrease these events. Furthermore, expanding the role of laparoscopy in the treatment of older patients with colon cancer may decrease rates of postoperative complications. Copyright © 2011 by Lippincott Williams & Wilkins. Source

Gomez V.,Mayo Medical School | Shahid M.W.,Mayo Medical School | Heckman M.G.,Section of Biostatistics | Crook J.E.,Section of Biostatistics | Wallace M.B.,Mayo Medical School
Diseases of the Colon and Rectum | Year: 2013

Background: Probe-based confocal laser endomicroscopy may allow a strategy of "diagnose, resect, and discard" for small nonadvanced adenomas, but there are concerns about discarding polyps with advanced histology. Objective: The aim of this study was to evaluate the potential use of probe-based confocal laser endomicroscopy to aid in distinguishing low-grade from advanced colon adenomas. Design: Six observers, blinded to histopathology, scored 5 adenoma features and an overall diagnosis and confidence level for the diagnosis. SETTING: This study was conducted at single, tertiary care referral center. PATIENTS: Patients undergoing screening and surveillance colonoscopies and for whom an adenomatous polyp was removed were included. Interventions: A sample of 27 advanced adenomas and 120 nonadvanced adenomas were used in the study. An initial classification system was created with 10 advanced and 10 nonadvanced adenomas. The remaining 127 adenomas were scored by each observer in the validation portion of the study. Main Outcome Measures: The primary outcome measured was the accurate classification of advanced and nonadvanced adenomas. Results: Overall, across all 6 observers, the sensitivity in correctly classifying advanced adenomas was 43%, the negative predictive value was 89%, the specificity was 71%, and the positive predictive value was 19%. No single feature or combination of features as seen with probe-based confocal laser endomicroscopy consistently identified advanced adenomas. Limitations: Classification criteria were developed subjectively, and there was limited observer experience with probe-based confocal laser endomicroscopy use. Conclusions: Our initial attempt at creating classification criteria for probe-based confocal laser endomicroscopy did not consistently distinguish advanced from nonadvanced adenomas and, therefore, is not useful in applying a "diagnose, resect, and discard" strategy. However, further refinement of our probe-based confocal laser endomicroscopy classification scheme in future studies has potential to accurately detect advanced histology in colorectal polyps. © 2013 The ASCRS. Source

Andersen A.-M.N.,Copenhagen University | Andersen P.K.,Section of Biostatistics | Olsen J.,University of Aarhus | Gronbaek M.,Center for Alcohol Research | And 2 more authors.
International Journal of Epidemiology | Year: 2012

Background: Controversies still exist regarding the existence of a 'safe' level of alcohol intake during pregnancy. The aim of this study was to assess the risk of fetal death (spontaneous abortion and stillbirth) according to maternal alcohol consumption in a large Danish pregnancy cohort. Methods: A cohort study carried out within the framework of the Danish National Birth Cohort. A total of the 92 719 participants enrolled in the Danish National Birth Cohort who provided information about lifestyle during first trimester of pregnancy were included in the study. Information about average weekly consumption of alcohol during pregnancy, smoking, coffee drinking, occupational status and reproductive history were obtained by means of computer-assisted telephone interviews. Pregnancy outcomes (spontaneous abortion, stillbirth, live birth and other pregnancy outcome) and gestational age at end of pregnancy were obtained through register linkage with the Civil Registration System and the National Discharge Registry. Data were analysed using Cox regression models, taking the varying gestational age at recruitment and time-dependent co-variables into account. Results: Fifty-five per cent of the participants abstained from alcohol drinking during pregnancy and only 2.2% reported four or more drinks per week. The adjusted hazard ratios for fetal death in first trimester were 1.66 [95% confidence interval (CI) 1.43-1.92] and 2.82 (95% CI 2.27-3.49) for women who reported 2-31/2 drinks per week and 4 or more drinks per week, respectively, and 1.57 (95% CI 1.30-1.90) and 1.73 (95% CI 1.24-2.41) for fetal death during pregnancy weeks 13-16. No increased risk was found for fetal death after 16 weeks of pregnancy. Conclusions: Even low amounts of alcohol consumption during early pregnancy increased the risk of spontaneous abortion substantially. The results indicate that the fetus is particularly susceptible to alcohol exposure early in pregnancy. Published by Oxford University Press on behalf of the International Epidemiological Association © The Author 2012; all rights reserved. Source

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