Penile Autophotography Underestimates the Degree of Penile Curvature in Peyronie's Disease.

BACKGROUND: Penile curvature is the most debilitating symptom of Peyronie's disease (PD); the evaluation of the degree of angulation is essential for planning treatment strategy. However, the most used method of penile at-home autophotography (AHP) is associated with some potential pitfalls and discrepancies compared with different assessment methods. OBJECTIVE: To compare the degree of penile curvature quantified by AHP and in-office intracavernosal alprostadil injection (ICI) prior to therapy. DESIGN, SETTING, AND PARTICIPANTS: Data from 55 PD patients of a single tertiary referral center were analyzed. All patients provided standardized AHP of the erect phallus. Clinic-based assessment included ICI with curvature measurement and completion of the International Index of Erectile Function (IIEF-15). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The Wilcoxon and/or chi-square test was used to compare the degree of curvature obtained using AHP and ICI, and to evaluate whether erectile dysfunction was a predictor of a relevant difference of >10° in curvature assessment between AHP and ICI. RESULTS AND LIMITATIONS: Our study showed a significant (p < 0.001) difference in the degree of penile curvature between AHP (48° [38°; 55°]) and ICI (50° [40°; 65°]). Patients suffering from erectile dysfunction tend to have a higher difference in the degree of penile curvature between AHP and ICI than patients with good erectile function (p < 0.001). Our study is not devoid of limitations. First, we did not use Peyronie's Disease Questionnaire, as suggested by the European Association of Urology guidelines. Second, we did not evaluate inter- and intraobserver variations in the measurements. CONCLUSIONS: AHP tends to underestimate the extent of penile curvature compared to ICI. Erectile dysfunction is an independent predictor of measurement differences of >10° between AHP and ICI. PATIENT SUMMARY: It is necessary to evaluate the degree of penile curvature in Peyronie's disease prior to therapy decision. The at-home self-photography underestimates the real degree of penile curvature compared with an erection by in-office penile drug injection. Especially men suffering from erectile dysfunction carry the risk of a high difference in the measured degree of penile curvature, with a potential impact on the further treatment.

The ambiguous role of microRNA-205 and its clinical potential in pancreatic ductal adenocarcinoma.

PURPOSE: Early treatment of pancreatic ductal adenocarcinoma (PDAC) is significantly delayed due to the lack of liquid biopsy markers for early diagnosis at surgically resectable tumor stages. Recent studies suggest that microRNA-205 (miR-205) is involved in PDAC progression by post-transcriptional regulation of epithelial-to-mesenchymal transition (EMT). However, the clinical potential of miR-205 as diagnostic and prognostic marker remains undefined and its exact role in PDAC is still ambiguous. This retrospective study is a substantial contribution to this on-going scientific discussion. METHODS: Expression analysis of miR-205 and its molecular targets in PDAC cell lines (n = 5), human tissue (n = 73), and blood serum samples (n = 85) by qRT-PCR, tissue microarray immunohistochemistry, and western blot. Descriptive and explorative statistical analysis of miR-205's clinical potential for diagnosis and prognosis of PDAC. RESULTS: The expression of miR-205 differs more than 2000-fold (p < 0.001) between epithelial and mesenchymal-like human PDAC cell lines correlating with EMT-marker expression of E-cadherin, vimentin, fibronectin, and ZEB-1. Expression of miR-205 is significantly upregulated in carcinoma tissue (eightfold, p = 0.028) and serum (2.3-fold, p = 0.023) of PDAC patients compared to age-matched healthy controls. In our patient collective circulating miR-205 in combination with CA.19-9 outperforms the diagnostic accuracy of CA.19-9 alone with an AUC of 0.890 (p < 0.001), sensitivity of 0.867, and specificity of 0.933. Though non-significant, low expression of circulating miR-205 is more frequent in advanced tumor stages combined with a worse overall survival (6.9 vs. 11.9 months, p = 0.176). CONCLUSION: Besides its controversial role in carcinogenesis, miR-205 shows high potential as a solid and liquid biopsy marker in PDAC. This result is an urgent call for larger confirmatory multi-center studies.

Clinical Impact of Epithelial-to-Mesenchymal Transition Regulating MicroRNAs in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive carcinoma entities worldwide with early and rapid dissemination. Recently, we discussed the role of microRNAs as epigenetic regulators of Epithelial-to-Mesenchymal Transition (EMT) in PDAC. In this study, we investigated their value as diagnostic and prognostic markers in tissue and blood samples of 185 patients including PDAC, non-malignant pancreatic disorders, and age-matched healthy controls. Expression of the microRNA-200-family (microRNAs -141, -200a, -200b, -200c, -429) and microRNA-148a was significantly downregulated in tissue of PDAC Union internationale contre le cancer (UICC) Stage II. Correspondingly, stromal PDAC tissue showed strong expression of Fibronectin, Vimentin, and ZEB-1 (Zinc finger E-box-binding homeobox) versus low expression of E-cadherin. Transient transfection of microRNA-200b and microRNA-200c mimics resulted in the downregulation of their key target ZEB-1. Inversely, blood serum analyses of patients with PDAC UICC Stages II, III, and IV showed a significant over-expression of microRNA-200-family members, microRNA-148a, microRNA-10b, and microRNA-34a. Correspondingly, Enzyme-linked Immunosorbent Assay (ELISA) analyses revealed a significant over-expression of soluble E-cadherin in serum samples of PDAC patients versus healthy controls. The best diagnostic accuracy to distinguish between PDAC and non-PDAC in this patient collective could be achieved in tissue by microRNA-148a with an area under the receiver-operating-characteristic (ROC) curve (AUC) of 0.885 and in blood serum by a panel of microRNA-141, -200b, -200c, and CA.19-9 with an AUC of 0.890. Both diagnostic tools outreach the diagnostic performance of the currently most common diagnostic biomarker CA.19-9 (AUC of 0.834). Kaplan Meier survival analysis of this patient collective revealed an improved overall survival in PDAC patients with high expression of tissue-related microRNA-34a, -141, -200b, -200c, and -429. In conclusion, EMT-regulating microRNAs have great potential as liquid and solid biopsy markers in PDAC patients. Their prognostic and therapeutic benefits remain important tasks for future studies.