Scleroderma Renal Crisis: Clues From the Physical Exam.

Scleroderma renal crisis (SRC) is a rare, life-threatening complication of systemic sclerosis (SSc) and can sometimes be the first manifestation of the disease.1 A 56-year-old female presented with acute encephalopathy requiring intubation and a systolic blood pressure of 230 mmHg; no information was available about her medical history.

Perineural Invasion and Risk of Lethal Prostate Cancer.

Background: Prostate cancer has a propensity to invade and grow along nerves, a phenomenon called perineural invasion (PNI). Recent studies suggest that the presence of PNI in prostate cancer has been associated with cancer aggressiveness.Methods: We investigated the association between PNI and lethal prostate cancer in untreated and treated prostate cancer cohorts: the Swedish Watchful Waiting Cohort of 615 men who underwent watchful waiting, and the U.S. Health Professionals Follow-Up Study of 849 men treated with radical prostatectomy. One pathologist performed a standardized histopathologic review assessing PNI and Gleason grade. Patients were followed from diagnosis until metastasis or death.Results: The prevalence of PNI was 7% and 44% in the untreated and treated cohorts, respectively. PNI was more common in high Gleason grade tumors in both cohorts. PNI was associated with enhanced tumor angiogenesis, but not tumor proliferation or apoptosis. In the Swedish study, PNI was associated with lethal prostate cancer [OR 7.4; 95% confidence interval (CI), 3.6-16.6; P < 0.001]. A positive, although not statistically significant, association persisted after adjustment for age, Gleason grade, and tumor volume (OR 1.9; 95% CI, 0.8-5.1; P = 0.17). In the U.S. study, PNI predicted lethal prostate cancer independent of clinical factors (HR 1.8; 95% CI, 1.0, 3.3; P =0.04).Conclusions: These data support the hypothesis that perineural invasion creates a microenvironment that promotes cancer aggressiveness.Impact: Our findings suggest that PNI should be a standardized component of histopathologic review, and highlights a mechanism underlying prostate cancer metastasis. Cancer Epidemiol Biomarkers Prev; 26(5); 719-26. ©2017 AACR.

Selenium- or Vitamin E-Related Gene Variants, Interaction with Supplementation, and Risk of High-Grade Prostate Cancer in SELECT.

BACKGROUND: Epidemiologic studies and secondary analyses of randomized trials supported the hypothesis that selenium and vitamin E lower prostate cancer risk. However, the Selenium and Vitamin E Cancer Prevention Trial (SELECT) showed no benefit of either supplement. Genetic variants involved in selenium or vitamin E metabolism or transport may underlie the complex associations of selenium and vitamin E. METHODS: We undertook a case-cohort study of SELECT participants randomized to placebo, selenium, or vitamin E. The subcohort included 1,434 men; our primary outcome was high-grade prostate cancer (N = 278 cases, Gleason 7 or higher cancer). We used weighted Cox regression to examine the association between SNPs and high-grade prostate cancer risk. To assess effect modification, we created interaction terms between randomization arm and genotype and calculated log likelihood statistics. RESULTS: We noted statistically significant (P < 0.05) interactions between selenium assignment, SNPs in CAT, SOD2, PRDX6, SOD3, and TXNRD2, and high-grade prostate cancer risk. Statistically significant SNPs that modified the association of vitamin E assignment and high-grade prostate cancer included SEC14L2, SOD1, and TTPA In the placebo arm, several SNPs, hypothesized to interact with supplement assignment and risk of high-grade prostate cancer, were also directly associated with outcome. CONCLUSION: Variants in selenium and vitamin E metabolism/transport genes may influence risk of overall and high-grade prostate cancer, and may modify an individual man's response to vitamin E or selenium supplementation with regards to these risks. IMPACT: The effect of selenium or vitamin E supplementation on high-grade prostate cancer risk may vary by genotype. Cancer Epidemiol Biomarkers Prev; 25(7); 1050-8. ©2016 AACR.

The Initial Management and Endoscopic Outcomes of Dyspepsia in a Low-Risk Patient Population.

BACKGROUND AND AIMS: Dyspepsia is frequently encountered by primary care providers (PCP) and gastroenterologists (GI). While esophagogastroduodenoscopy (EGD) may be useful, current guidelines suggest a proton pump inhibitor (PPI) trial and H. pylori (HP) test-and-treat before EGD for low-risk patients. This study aimed to evaluate pre-EGD management and endoscopic outcomes in this population. METHODS: This was a retrospective cohort study of low-risk dyspepsia patients (age ≤55, no alarm features) undergoing EGD at an ambulatory endoscopy center from January 2011 to March 2012. Adherences to initial management guidelines (PPI trial and HP test-and-treat strategy before EGD) were compared between PCP and GI. Endoscopic and pathologic outcomes were assessed for all patients. Statistical analyses were performed using Chi-squared test (categorical variables) and Student's t test (continuous variables). This study received IRB approval (2011P001715). RESULTS: A total of 309 low-risk patients underwent EGD for dyspepsia. Only 202 (65.4 %) had HP testing, and 220 (71.2 %) were trialed on any dose/length PPI pre-EGD, with no differences between PCP and GI. PPI exposure was similar between groups for all dose/duration except for trials ≥8 weeks of any dose (46.9 % GI vs 34.3 % PCP, p = 0.03) and high dose (32 % GI vs 18.7 % PCP, p = 0.01). Overall, only 178 (57.6 %) patients had both HP testing and any PPI exposure pre-EGD (56.6 % GI vs 59 % PCP, p = 0.73). Significant pathology was rare, with gastritis (46.6 %) and HP (17.2 %) being most common. No malignancy was found. CONCLUSIONS: A significant proportion of low-risk dyspepsia patients did not receive any PPI trial or HP testing before EGD. Within this population, significant finding on EGD was rare, supporting the current noninvasive initial management guidelines for dyspepsia.