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Supplementary Table 3: Multivariable Linear Regressions between Log Continous Serum and Tissue Hormones Stratified by Gleason Score

Supplementary Table 2: Reproducibility of average tissue hormone assays by zone and overall from a pilot study of 30 men recruited at George Washington University Medical Center that included a total of 171 prostate biopsies.

Supplementary Table 1: Reproducibility of serum and tissue hormone assays used for the main analysis

Supplementary Table 4: Multivariable Linear Regressions between Log Continous Serum and Tissue Hormones Stratified by Race

Supplementary Table 5: Multivariable Linear Regressions between Log Continous Serum and Tissue Hormones Stratified by Median Age at Blood Draw

Background: Sex hormones have been implicated in prostate carcinogenesis, yet epidemiologic studies have not provided substantiating evidence. We tested the hypothesis that circulating concentrations of sex steroid hormones reflect intraprostatic concentrations using serum and adjacent microscopically verified benign prostate tissue from prostate cancer cases.Methods: Incident localized prostate cancer cases scheduled for surgery were invited to participate. Consented participants completed surveys, and provided resected tissues and blood. Histologic assessment of the ends of fresh frozen tissue confirmed adjacent microscopically verified benign pathology. Sex steroid hormones in sera and tissues were extracted, chromatographically separated, and then quantitated by radioimmunoassays. Linear regression was used to account for variations in intraprostatic hormone concentrations by age, body mass index, race, and study site, and subsequently to assess relationships with serum hormone concentrations. Gleason score (from adjacent tumor tissue), race, and age were assessed as potential effect modifiers.Results: Circulating sex steroid hormone concentrations had low-to-moderate correlations with, and explained small proportions of variations in, intraprostatic sex steroid hormone concentrations. Androstane-3α,17β-diol glucuronide (3α-diol G) explained the highest variance of tissue concentrations of 3α-diol G (linear regression r2 = 0.21), followed by serum testosterone and tissue dihydrotestosterone (r2 = 0.10), and then serum estrone and tissue estrone (r2 = 0.09). There was no effect modification by Gleason score, race, or age.Conclusions: Circulating concentrations of sex steroid hormones are poor surrogate measures of the intraprostatic hormonal milieu.Impact: The high exposure misclassification provided by circulating sex steroid hormone concentrations for intraprostatic levels may partly explain the lack of any consistent association of circulating hormones with prostate cancer risk. Cancer Epidemiol Biomarkers Prev; 26(11); 1660–6. ©2017 AACR.

Background: Sex hormones have been implicated in prostate carcinogenesis, yet epidemiologic studies have not provided substantiating evidence. We tested the hypothesis that circulating concentrations of sex steroid hormones reflect intraprostatic concentrations using serum and adjacent microscopically verified benign prostate tissue from prostate cancer cases. Methods: Incident localized prostate cancer cases scheduled for surgery were invited to participate. Consented participants completed surveys, and provided resected tissues and blood. Histologic assessment of the ends of fresh frozen tissue confirmed adjacent microscopically verified benign pathology. Sex steroid hormones in sera and tissues were extracted, chromatographically separated, and then quantitated by radioimmunoassays. Linear regression was used to account for variations in intraprostatic hormone concentrations by age, body mass index, race, and study site, and subsequently to assess relationships with serum hormone concentrations. Gleason score (from adjacent tumor tissue), race, and age were assessed as potential effect modifiers. Results: Circulating sex steroid hormone concentrations had low-to-moderate correlations with, and explained small proportions of variations in, intraprostatic sex steroid hormone concentrations. Androstane-3α,17β-diol glucuronide (3α-diol G) explained the highest variance of tissue concentrations of 3α-diol G (linear regression r2 = 0.21), followed by serum testosterone and tissue dihydrotestosterone (r2 = 0.10), and then serum estrone and tissue estrone (r2 = 0.09). There was no effect modification by Gleason score, race, or age. Conclusions: Circulating concentrations of sex steroid hormones are poor surrogate measures of the intraprostatic hormonal milieu. Impact: The high exposure misclassification provided by circulating sex steroid hormone concentrations for intraprostatic levels may partly explain the lack of any consistent association of circulating hormones with prostate cancer risk. Cancer Epidemiol Biomarkers Prev; 26(11); 1660–6. ©2017 AACR.

BACKGROUND Prospective cohort studies of circulating sex steroid hormones and prostate cancer risk have not provided a consistent association, despite evidence from animal and clinical studies. However, studies using male pattern baldness as a proxy of early-life or cumulative androgen exposure have reported significant associations with aggressive and fatal prostate cancer risk. Given that androgens underlie the development of patterned hair loss and chest hair, we assessed whether these two dermatological characteristics were associated with circulating and intraprostatic concentrations of sex steroid hormones among men diagnosed with localized prostate cancer. METHODS We included 248 prostate cancer patients from the NCI Prostate Tissue Study, who answered surveys and provided a pre-treatment blood sample as well as fresh frozen adjacent normal prostate tissue. Male pattern baldness and chest hair density were assessed by trained nurses before surgery. General linear models estimated geometric means and 95% confidence intervals (95%CIs) of each hormone variable by dermatological phenotype with adjustment for potential confounding variables. Subgroup analyses were performed by Gleason score (

The case definition for inflammatory breast cancer (IBC) is controversial. The American Joint Committee on Cancer defines IBC as redness, warmth and edema involving at least half the breast. The SEER program relies on a pathologic finding of dermal lymphatic invasion and recently added those with clinical involvement of more than 3/4 of the breast. We established a registry to collect information and specimens from IBC patients to clarify the epidemiology and biology of these tumors. The goals of this report are to suggest improvements regarding case definitions and provide data on the variety of presentations relevant to early diagnosis.

Following an appendectomy, surgeons define appendicitis, for treatment and billing purposes, into one of four categories: normal appendix, acute appendicitis, gangrenous appendicitis, and perforated appendicitis. Treatment of appendicitis is predicated upon classification at the time of visual inspection. Further, this classification often plays a role in the assessment of hospital outcomes. The currently accepted classification system is based solely upon intraoperative surgeon opinion and not objective data. Inconsistent surgeon grading of the severity of appendicitis may have implications in both management and outcomes.The aim of this study was to assess the interobserver variation among surgeons in grading of the inflammatory severity of acute appendicitis as recognized on visual findings at operation.A cross-sectional study design. 110 surgeons, and surgical residents were randomly selected. Surgeons were shown images of intraoperative appendicitis and were asked to evaluate the severity of the appendicitis (i.e., normal, inflamed, gangrenous, and perforated). Demographic information regarding the type of practice, hospital setting, and the number of encounters with patients with acute appendicitis were assessed. An Intraclass Correlation Coefficient score, represented by R, was calculated to assess interobserver reliability in grading the inflammatory severity of acute appendicitis. The two-way analysis of variance procedure for multivariate analysis was used for this calculation.The study group consisted of 100 surgeons, 62 practicing surgeons, and 48 surgical trainees. Overall, 79% of the surgeons treated predominantly adults with appendicitis, 18% treated primarily children, and 3% treated both children and adults. Hospital practices included university hospitals (47%), community hospitals (33%), children's hospitals (14%), and others (6%). Overall, there was poor agreement among surgeons in assessing the severity of appendicitis. Among all attending surgeons, the agreement of defining an image as to whether it was perforated or not was 27% (R4 = 0.27). Completion of a general surgery residency did improve the interobserver agreement, when compared with trainees.There is poor agreement among surgeons in describing the severity of appendicitis. Treatment protocols based on more accurate assessment and categorization could potentially lead to more favorable, cost-effective outcomes. Further, studies determining efficacy in the diagnosis and treatment of appendicitis should consider observer variability. Future work must attempt to define critical objective assessment points, such as visible discontinuity of the appendix or fecal soilage, to assure a better correlation of findings with prognosis.

Marjorie K Mau1, Karynna Asao2, Jimmy Efird3, Erin Saito, Robert Ratner4, Muhannad Hafi4, Todd Seto51Department of Native Hawaiian Health; 3Biostatistics and Data Management Facility; 5Department of Medicine, John A. Burns School of Medicine, University of Hawai’i at Manoa; 2Claremont College; 4Medstar Research InstituteObjective: Heart failure (HF), a long term outcome of chronic methamphetamine use (MU), occurs more frequently in racial and ethnic minority populations at high risk for cardiovascular disparities. This study examined the association of socio-demographic and clinical risk factors with MU among heart failure patients who are Native Hawaiians (NH) or other Pacific Island peoples (PIP).Design/Setting/Patient population: Cross-sectional study of NHs and PIPs with advanced heart failure enrolled in the Malama Pu’uwai Study, a randomized control trial to test an educational intervention to reduce re-hospitalization and/or death. A total of 82 participants were enrolled between 6/1/06 to 12/31/07 and met the following eligibility criteria: 1) self-identified NH or PIP, 2) Left ventricular systolic ejection fraction ≤45%, 3) Age of 21 years or older. Data were analyzed by odds ratios (OR), 95% confidence intervals (CI), and multiple logistic regression analysis.Main outcome measure: Methamphetamine use.Results: Twenty-two percent of HF participants were identified as being current or prior methamphetamine users. Younger age and non-married status (combined never married or divorced/separated) were independently associated with MU after adjustment for sex, education, and other co-morbidities associated with HF (ie, age >50 years, OR = 0.16, 95% CI, 0.03–0.84; non-married status combined as never married OR = 8.5, CI, 1.5–47; divorced/separated OR = 11, CI 1.8–75).Conclusions: Risk factors associated with MU in NH and PIPs with heart failure include: younger age and being divorced/separated or never married. Health care providers should be aware of MU as a contributing factor in the approach and treatment of HF in NHs and PIPs.Keywords: Native Hawaiian and other Pacific Islander, ethnic minority, methamphetamine use, heart failure