Histological alterations in cavernous tissue after radical prostatectomy.

PURPOSE: Radical prostatectomy often results in erectile dysfunction because of lesions to the erectile nerves. In this study we evaluated histomorphological alterations in cavernous smooth muscle and collagen content after radical prostatectomy. MATERIALS AND METHODS: A total of 19 patients between 57 and 69 years old with prostate adenocarcinoma and normal erectile function, as reported and validated by RigiScan (UroHealth Systems, Laguna Niguel, California) testing, underwent corpora cavernosa biopsy in the operating room before radical prostatectomy, and 2 and 12 months after surgery. No patient underwent hormone therapy before or after surgery and none was diabetic. Elastic fibers (manual counting), muscle specific actin (immunostaining) and collagen content (computerized morphometric imaging) were measured in the 3 biopsies. RESULTS: In all cases the first postoperative histological assessment revealed some disorganization. Trabecular elastic fibers (p <0.0003) and smooth muscle fibers were decreased and collagen content was significantly increased (p <0.0003) compared with preoperative biopsies. One year after surgery elastic fibers (p <0.0003) and smooth muscle fibers were decreased and collagen content was significantly increased (p <0.0003) compared with the first postoperative biopsy. Moreover, organized collagen and trabecular protocollagen deposits were increased. CONCLUSIONS: Progressive fibrosis in the corpora cavernosa after radical prostatectomy probably results from denervation and/or an ischemic process, which is caused in turn by the ligation of anomalous pudendal artery branches or of venous plexuses that drain to or from the corpora cavernosa. Fibrosis and the subsequent loss in elasticity and function of erectile tissue probably together cause erectile dysfunction.

Association between vitamin D receptor gene polymorphisms and fasting idiopathic hypercalciuria in recurrent stone-forming patients.

OBJECTIVES: To investigate the association between fasting idiopathic hypercalciuria (IHc), defined as IHc in the fasting state associated with normal parathyroid function, and ApaI, BsmI, and FokI polymorphisms of the vitamin D receptor (VDR) gene in 159 hypercalciuric recurrent stone formers. IHc contributes to the formation of calcium kidney stones in more than one half of reported cases. METHODS: We examined 62 patients with fasting IHc (24 women, mean age 42.8 +/- 11.1 years, body mass index 25.7 +/- 4.8 kg/m2), 97 patients with absorptive IHc (41 women, mean age 43.5 +/- 10.8 years, body mass index 26.1 +/- 4.4 kg/m2), and 124 healthy control subjects (52 women, mean age 41.9 +/- 10.4 years, body mass index 25.4 +/- 5.1 kg/m2) without a history of nephrolithiasis and without IHc. The bone mass density and VDR genotype and haplotype frequencies were determined in the studied populations. RESULTS: A reduced bone mass density was observed in fasting IHc patients compared with absorptive IHc patients (P = 0.009) and control subjects (P = 0.006). The prevalence of ApaI and BsmI VDR genotypes and alleles in patients with fasting IHc was significantly different statistically (P <0.05) from that observed in patients with absorptive IHc and control subjects, and the ba haplotype was overrepresented in these patients. No statistically significant difference in the distribution of FokI VDR genotypes and alleles was found between the studied groups. CONCLUSIONS: Our results suggest a genetic association between 3' VDR alleles, fasting IHc, and reduced bone mass density in patients with recurrent stone formation.

The relationship of 3' vitamin D receptor haplotypes to urinary supersaturation of calcium oxalate salts and to age at onset and familial prevalence of nephrolithiasis.

BACKGROUND: Idiopathic hypercalciuria (IHc) and idiopathic hypocitraturia are frequently associated with calcium nephrolithiasis. We investigated the relationship of vitamin D receptor (VDR) polymorphisms (BsmI, TaqI and FokI) to urinary supersaturation of calcium oxalate salts in recurrent calcium oxalate stone formers with IHc and the clinical relevance of this relationship. METHODS: The study included 110 Caucasian stone formers with IHc and 127 unrelated healthy controls without history of nephrolithiasis. Age at onset of nephrolithiasis, familial history score (FHS) and the ion activity product of calcium oxalate salts in urine (AP(CaOx)) were tabulated. BsmI, TaqI and FokI VDR polymorphisms were evaluated in all participants. RESULTS: Patients and controls were classified as homozygous (bbTT and BBtt) or heterozygous in relation to BsmI and TaqI polymorphisms. Compared with BBtt patients, bbTT homozygous stone formers showed lower citrate excretion (1.91+/-0.89 vs 3.46+/-1.39 mmol/24 h, P = 0.004) and higher AP(CaOx) (2.02+/-0.51 vs 1.53+/-0.53, P = 0.006). Among controls, there were similar differences in citrate excretion and AP(CaOx) between the two groups, but they were not statistically significant. Compared with BBtt, bbTT patients showed lower mean age at onset of nephrolithiasis (29.7+/-12.1 vs 38.1+/-12.7 years, P = 0.008) and higher values of FHS (2.45+/-1.9 vs 0.83+/-0.7, P = 0.006). Similar results were obtained for individual BsmI and TaqI alleles. The analysis of FokI alleles was not informative. CONCLUSIONS: Recurrent calcium oxalate stone formers with IHc and the bT VDR haplotype have more aggressive kidney stone diseases as indicated by a higher familial incidence and lower mean age at onset. This clinical severity is associated with the higher urinary supersaturation of calcium oxalate salts and abnormalities of renal citrate handling.