The pathophysiology of Peyronie’s disease

OBJECTIVE: To review the contemporary knowledge of the pathophysiology of Peyronie’s disease (PD). METHODS: Medline was searched for papers published in English from 2000 to March 2013, using the keywords ‘Peyronie’s disease’ and ‘pathophysiology’. RESULTS: More than 300 relevant articles were identified for the purpose of this review. Unfortunately only a few studies had a high level of evidence, and the remaining studies were not controlled in their design. Many theories have been proposed to explain the cause of PD, but the true pathogenesis of PD remains an enigma. Identifying particular growth factors and the specific genes responsible for the induction of PD have been the ultimate goal of research over the past several decades. This would provide the means to devise a possible gene therapy for this devastating condition. We discuss present controversies and new discoveries related to the pathophysiology of this condition. CONCLUSION: PD is one of the most puzzling diseases in urology. The pathogenesis remains uncertain and there is still controversy about the best management. The pathogenesis of PD has been explored in animal models, cell cultures and clinical trials, but the results have led to further questions. New research on the aetiology and pathogenesis of PD is needed, and which will hopefully improve the understanding and management for patients with this frustrating disease

Histopathologic and clinical comparison of recurrent and non-recurrent urethral stricture disease treated by reconstructive surgery

BACKGROUND: Urethral stricture is a relatively frequent problem often requiring multiple surgical interventions. The objective of this study was to compare the clinicopathologic features of urethral resections from patients who underwent open end-to-end anastomotic urethroplasty and later recurred compared to those who did not. METHODS: A retrospective review of the pathology files identified 36 consecutive patients who underwent urethroplasty. The histopathological analysis included evaluation of the inflammatory infiltrate based on the predominant (>50%) cell type: lymphocyte-rich, neutrophil-rich, plasma cell-rich, and mixed; length and thickness of the fibrous plaque; and the cellularity of the fibrous plaque: cellular (>40 stroma nuclei/HPF) or paucicellular (<40 stroma nuclei/high power field). RESULTS: Ten (28%) patients recurred, and 26 (72%) did not. There was no significant difference between recurrent and non-recurrent cases in age, race, comorbidities, location of the stricture, and etiology. All patients with recurrent strictures showed dense paucicellular fibrotic plaques (10/10; 100%), while this was seen in 14/26 (53.8%) non-recurrent cases (P=0.01). Only one patient with cellular fibrosis showed recurrence during follow-up. The log-rank test shows that time to recurrence is significantly shorter in patients with paucicellular fibrosis compared to those with cellular fibrosis (P=0.036). The inflammation consisted of a mixed population of CD3(+) T-lymphocytes, CD20(+) B-lymphocytes, and CD68(+) histiocytes, and there was no difference in the composition of the inflammation between groups. All cases with plasma cell-rich infiltrate showed normal IgG4:IgG. CONCLUSIONS: Our study supports reporting cellularity of the fibrous plaque as a potential predictor of outcome in patients undergoing reconstructive urethroplasty. Patients with paucicellular fibrosis are at increased risk of recurrence

Beneficial Effect Of The Nitric Oxide Donor Compound 3-(1,3-dioxoisoindolin-2-yl) Benzyl Nitrate On Dysregulated Phosphodiesterase 5, Nadph Oxidase, And Nitrosative Stress In The Sickle Cell Mouse Penis: Implication For Priapism Treatment

Patients with sickle cell disease (SCD) display priapism, and dysregulated nitric oxide (NO) pathway may contribute to this condition. However, current therapies offered for the prevention of priapism in SCD are few. The 3-(1,3-dioxoisoindolin-2-yl)benzyl nitrate (compound 4C) was synthesized through molecular hybridization of hydroxyurea and thalidomide, which displays an NO-donor property. This study aimed to evaluate the effects of compound 4C on functional and molecular alterations of erectile function in murine models that display low NO bioavailability, SCD transgenic mice, and endothelial NO synthase and neuronal NO synthase double gene-deficient (dNOS2/) mice, focusing on the dysregulated NO-cGMP-phosphodiesterase type 5 (PDE5) pathway and oxidative stress in erectile tissue. Wild-type, SCD, and dNOS-/- mice were treated with compound 4C (100 μmol/kg/d, 3 weeks). Intracavernosal pressure in anesthetized mice was evaluated. Corpus cavernosum tissue was dissected free and mounted in organ baths. SCD and dNOS-/- mice displayed a priapism phenotype, which was reversed by compound 4C treatment. Increased corpus cavernosum relaxant responses to acetylcholine and electrical-field stimulation were reduced by 4C in SCD mice. Likewise, increased sodium nitroprusside-induced relaxant responses were reduced by 4C in cavernosal tissue from SCD and dNOS-/- mice. Compound 4C reversed PDE5 protein expression and reduced protein expressions of reactive oxygen species markers, NADPH oxidase subunit gp91phox, and 3-nitrotyrosine in penises from SCD and dNOS-/- mice. In conclusion, 3-week therapy with the NO donor 4C reversed the priapism in murine models that display lower NO bioavailability. NO donor compounds may constitute an additional strategy to prevent priapism in SCD. © 2016 by The American Society for Pharmacology and Experimental Therapeutics.3592230237R01DK067223, NIDDK, National Institute of Diabetes and Digestive and Kidney DiseasesNIH, National Institutes of Healt