Adriano Fregonesi

Erectile dysfunction and hormonal imbalance in morbidly obese male is reversed after gastric bypass surgery: a prospective randomized controlled trial

The effects of weight loss on erectile function and hormones have not been well studied. The aim of this study was to measure the degree to which sexual function and in particular erectile function and hormonal environment change after substantial weight loss, surgically and non-surgically induced in the morbidly obese male in a prospective randomized long-term controlled trial. Furthermore, how surgery makes a difference when treating morbidly obese men was envisaged in this context. We prospectively studied 20 morbidly obese men for 24 months, divided into two groups: group A included 10 patients who underwent life style modifications (exercise and diet) for 4 months and subsequently gastric bypass, and another 10 patients in group B were kept on weekly follow-up. None of the men were taking phosphodiesterase type-5 inhibitors. All patients underwent International Index of Erectile Function (IIEF)-5 questionnaire, serum oestradiol, prolactin (PRL), luteinizing (LH) and follicle-stimulating (FSH) hormones, free and total testosterone (FT and TT) at baseline (time 0), surgery - 4 months latter baseline (time 1) and final evaluation - 24 months (time 2). From times 0 to 1, group A presented a mean body mass index (BMI) reduction of 12.6 (p < 0.0001), whereas group B, 2.1 (p > 0.05). The BMI reductions between times 0 and 2 were 24.7 (p < 0.0001) and 0.7 (p > 0.05) for groups A and B respectively. BMI average between the two groups was similar at time 0 (p = 0.2142), and different at times 1 (p = 0.0033) and 2 (p < 0.0006). Increase in IIEF-5 score (p = 0.0469), TT (p = 0.0349) and FSH levels (p = 0.0025), and reduction in PRL level (p < 0.0001) were observed in group A from times 0 to 2 and 1 to 2. There were no changes from times 0 to 1. Comparing groups A and B at time 2, IIEF-5, TT and FT increased significantly in group A (p = 0.0224, 0.0043 and 0.0149 respectively). Surgery-induced weight loss increased erectile function quality measured by IIEF-5 questionnaire, increased TT, FT and FSH and reduced PRL levels. The hormonal impact verified could justify the improvement in erectile function. Lifestyle modifications impacted BMI without hormonal or sexual impact in morbidly obese. New studies are warranted in the field to support our data.

Bariatric Surgery Does not Interfere With Sperm Quality—A Preliminary Long-Term Study

Purpose: Positive impact of weight loss on sexual function and hormones has been demonstrated, and male fertility in this scenario is to be better defined. We evaluated the impact of lifestyle modifications and gastric bypass on sperm quality. Methods: We prospectively studied 20 morbidly obese men during 24 months, randomized for intervention: lifestyle modifications (exercise and diet) for 4 months and subsequently gastric bypass (n = 10); and control: follow-up (n = 10). All patients underwent International Index of Erectile Function (IIEF-5) questionnaire, serum estradiol, prolactin (PRL), luteinizing and follicle-stimulating hormones (LH and FSH), free and total testosterones (FT and TT) and semen analysis at baseline (time 0), surgery 4 months later baseline (time 1) and final evaluation 24 months (time 2). Results: Intervention group presented significant reduction in body mass index (BMI) at times 1 and 2, compared to control. There were no significant differences among sperm parameters between groups at times 0, 1, and 2 and among times 0, 1, and 2 in each group. Increases in IIEF-5 score (P = .0469), TT (P = .0349), and FSH (P = .0025) and reduction in PRL (P < .0001) were observed in the intervention group from times 0 to 2 and 1 to 2. Comparing groups at time 2, IIEF-5, TT, and FT increased significantly in the intervention group (P = .0224, P = .0043, and P = .0149, respectively). Conclusions: Surgery-induced massive weight loss does not interfere with sperm quality, while it increased the quality of sexual function, TT, FT and FSH and reduced PRL. Lifestyle modifications impacted merely the BMI. New studies are warranted, mostly considering birth rate as primary end point and including infertile men.

Nitric oxide release from human corpus cavernosum induced by a purified scorpion toxin.

OBJECTIVES To investigate the effects of a purified scorpion toxin (Ts3) on human corpus cavernosum (HCC) in vitro. Scorpion venoms cause a massive release of neurotransmitters that contribute to the clinical symptoms resulting from envenomation. METHODS HCC strips were mounted in organ baths containing Krebs solution. After equilibration, the tissues were precontracted with phenylephrine (10 micromol/L). The relaxations caused by Ts3 (30 nmol/L) were compared with those induced by electrical field stimulation (1 to 20 Hz) and nitric oxide (NO, 1 to 100 micromol/L). RESULTS The addition of Ts3 evoked long-lasting relaxations of precontracted HCC strips, and exogenously applied NO and electrical field stimulation caused short-lived responses. The NO synthesis inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME; 100 micromol/L) reduced by 87% +/- 2% the Ts3-induced relaxations; this inhibition was reversed by pretreating the tissues with L-arginine (1 mmol/L). The relaxant responses mediated by Ts3 were blocked to a similar degree by the soluble guanylyl cyclase inhibitor 1H-[1,2,4] oxadiazolo [4,3,-alquinoxalin-1-one] (10 micromol/L). In contrast, the addition of the phosphodiesterase type 5 inhibitor sildenafil (0.1 micromol/L) significantly enhanced Ts3-evoked relaxations by 78% +/- 4%. The sodium channel blocker tetrodotoxin (1 micromol/L) completely blocked the relaxant responses elicited by both Ts3 and electrical field stimulation, without significantly affecting those elicited by NO. CONCLUSIONS The results indicate that Ts3 relaxes the HCC through the release of NO from nitrergic nerves. The elucidation of this mechanism is useful for the development of new therapeutic strategies to treat priapism after scorpion envenomation or to modulate sodium channel activity in the case of penile dysfunction.

Challenges on percutaneous nephrolithotomy in pregnancy: Supine position approach through ultrasound guidance

Urolithiasis in pregnancy represents a major diagnostic and therapeutic challenge to the obstetrician, urologist, radiologist and anesthetist. It is a cause of major concern, considering the potential adverse effects of radiation exposure and of any invasive surgical procedure and anesthesia on the mother and fetus. Fortunately, with conservative management, 70-80% of symptomatic calculi pass spontaneously with no sequel. However, fever, infection, uncontrolled pain and progressive hydronephrosis are indications for surgical intervention when retrograde placements of a ureteral stent or a percutaneous nephrostomy tube are the most traditional options. The recent technological advances in stone fragmentation devices and the administration of safe anesthesia have forced clinicians to embark on more definitive stone management techniques in pregnancy. Ureteroscopy is considered the first definitive treatment of obstructive ureteral calculi during all trimesters of pregnancy, but also has limitations. Although generally avoided during pregnancy, percutaneous nephrolithotomy can be a good treatment choice in selected patients.

Vascular Modifications of the Clitoris Induced by Topic Nitric Oxide Donor Gel—Preliminary Study

INTRODUCTION The clitoral blood flow increase is dependent of nitric oxide (NO) and it occurs due to sexual arousal. Female sexual disorder mechanisms are poorly understood and NO therapeutic role in this scenario is to be determined. AIM To assess topic NO donor S-nitrosoglutationa (GSNO) gel-100 µM effect on clitoral blood flow in healthy women. METHODS Forty healthy women were double-blinded randomized for Group 1, GSNO gel, n=20 and Group 2, placebo gel, n=20. All patients underwent Doppler ultrasound test in the clitoral artery. Hemodynamic analysis consisted of: systolic peak speed, diastolic speed, and vase resistance rate. Ten random patients were analyzed regarding sexual function after two double-blinded placebo and NO donor gel periods of 30 days. MAIN OUTCOME MEASURES To consider female sexual dysfunction treatment through local NO-dependent pathway. RESULTS Mean age was 31 years (20-39) and mean female sexual function index score 31.5 (26-34). Group 1: The mean and standard deviation baseline and 15 minutes after the application of the GSNO gel systolic (11.7±2.1 cm/second to 15.9±2.4 cm/second) and diastolic speeds (2.7±0.3 cm/second to 4.2±0.4 cm/second) and resistance (0.71±0.04 to 1.38±0.06) were significantly increased (P=0.002) (P=0.043), and (P=0.005), respectively. No local or systemic adverse effect was observed in women or in their sexual partners and the sexual function presented a slightly insignificant improvement (P=0.065), although eight of 10 women could subjectively identify the GSNO gel as the preferred and most pleasant between both tried. Group 2 presented no significant differences at baseline and 15 minutes after the application of the placebo gel, P>0.05. CONCLUSION The topic GSNO gel increased significantly the clitoral blood flow and could be considered therapeutically in selected cases of female sexual dysfunction warranting further investigation.

Comparative Relaxing Effects of Sildenafil, Vardenafil, and Tadalafil in Human Corpus Cavernosum: Contribution of Endogenous Nitric Oxide Release

OBJECTIVES To compare the direct relaxant activity of sildenafil, vardenafil, and tadalafil in the human corpus cavernosum (HCC) and to investigate their modulatory effects on nitric oxide (NO)-mediated responses. Phosphodiesterase (PDE)-5 inhibitors cause cavernosal smooth muscle relaxation and penile erection. METHODS HCC strips were mounted in 10-mL organ baths containing Krebs solution and connected to force-displacement transducers. The changes in isometric force were recorded using the Powerlab 400 data acquisition system. Corporeal smooth muscle was precontracted submaximally with phenylephrine (10 micromol/L). RESULTS All PDE-5 inhibitors tested (0.001-10 micromol/L) relaxed phenylephrine-precontracted HCC with similar values of potency in a concentration-dependent manner. However, the maximal relaxations induced by tadalafil (83% +/- 4%) were significantly lower compared with sildenafil (107% +/- 5%) and vardenafil (111% +/- 3%). The NO synthesis inhibitor N-nitro-l-arginine methyl ester (100 micromol/L) caused significant rightward shifts in the concentration-response curves for sildenafil (4.0-fold), vardenafil (4.6-fold), and tadalafil (3.2-fold) in HCC tissue. The guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10 micromol/L) also produced similar rightward shifts for these PDE-5 inhibitors. The cavernosal relaxations evoked by either acetylcholine or the NO donor glyceryl trinitrate were markedly potentiated by sildenafil, vardenafil, and tadalafil (0.1 micromol/L each). All PDE-5 inhibitors significantly increased the duration of electrical field stimulation-induced relaxations (8 Hz). CONCLUSIONS Our findings have shown that sildenafil, vardenafil, and tadalafil relax HCC tissues in a concentration-dependent manner, but the maximal relaxation obtained with tadalafil was significantly lower than that obtained with sildenafil and vardenafil. Moreover, the PDE-5 inhibitors interacted with endogenous and exogenous NO, amplifying its HCC relaxation.

Validation of Portuguese version of Quality of Erection Questionnaire (QEQ) and comparison to International Index of Erectile Function (IIEF) and RAND 36-Item Health Survey

Purpose To validate the Quality of Erection Questionnaire (QEQ) considering Brazilian social-cultural aspects. Materials and Methods To determine equivalence between the Portuguese and the English QEQ versions, the Portuguese version was back-translated by two professors who are native English speakers. After language equivalence had been determined, urologists considered the QEQ Portuguese version suitable. Men with self-reported erectile dysfunction (ED) and infertile men who had a stable sexual relationship for at least 6 months were invited to answer the QEQ, the International Index of Erectile Function (IIEF) and the RAND 36-Item Health Survey (RAND-36). The questionnaires were presented together and answered without help in a private room. Internal consistency (Cronbach’s α), test-retest reliability (Spearman), convergent validity (Spearman correlation) coefficients and known-groups validity (the ability of the QEQ Portuguese version to differentiate erectile dysfunction severity groups) were assessed. Results We recruited 197 men (167 ED patients and 30 non-ED patients), mean age of 53.3 and median of 55.5 years (23-82 years). The Portuguese version of the QEQ had high internal consistency (Cronbach α=0.93), high stability between test and retest (ICC 0.83, with IC 95%: 0.76-0.88, p<0.001) and Spearman correlation coefficient r=0.82 (p<0.001), which demonstrated the high correlation between the QEQ and IIEF results. The correlations between the QEQ and RAND-36 were significantly low in ED (r=0.20, p=0.01) and non-ED patients (r=0.37, p=0.04). Conclusion The QEQ Portuguese version presented good psychometric properties and high convergent validity in relation to IIEF. The low correlations between the QEQ and the RAND-36, as well as between the IIEF and the RAND-36 indicated IIEF and QEQ specificity, which may have resulted from the patients’ psychological adaptations that minimized the impact of ED on Quality of Life (QoL) and reestablished the well-being feeling.

Strategies for transfusion-free radical retropubic prostatectomy in Jehovah's witnesses

OBJECTIVES While radical retropubic prostatectomy carries significant potential for blood loss requiring transfusion, Jehovahs Witnesses do not permit the use of allogeneic blood products. This study presents strategies for transfusion-free radical retropubic prostatectomy for prostate cancer treatment in Jehovahs Witnesses patients. METHODS From March 1998 to May 2009, 25 Jehovahs Witnesses patients diagnosed with prostate cancer underwent radical prostatectomy and bilateral iliac and obturatory lymphadenectomy. Preoperative hemoglobin boost utilizing erythropoietin aiming hemoglobin over 14 g/dL, normovolemic hemodilution and availability of cell salvage machine were provided for blood loss management. RESULTS The mean age was 62 (43 to 70) years and the mean hospitalization time was 3.5 (3 to 7) days. Mean intra-operative bleeding was 430 (+/-120) ml and the mean pre- and post-operative hemoglobin (measured before discharge) was 15.1 (+/-0.8) and 11.7 (+/-2.3) g/dL, respectively. There was no need for cell salvage machine or transfusion. The lowest hemoglobin was 5.7 g/dL due to post-operative bladder neck bleeding, which responded to twenty days of office based erythropoietin subcutaneously on alternate days reaching 12 g/dL hemoglobin. There was no complication related to non-transfusion. CONCLUSIONS The proposed techniques were essential for maximum reduction of the need for transfusions without increasing complications. Further studies are needed to introduce these methods in all cases of radical retropubic prostatectomy regarding the benefits in lowering costs and risks related to transfusion.

Liquid silicone used for esthetic purposes as a potentiator for occurrence of post-radiotherapy genital lymphedema: case report.

CONTEXT: Lymphedema consists of extracellular fluid retention caused by lymphatic obstruction. In chronic forms, fat and fibrous tissue accumulation is observed. Genital lymphedema is a rare condition in developed countries and may have primary or acquired etiology. It generally leads to urinary, sexual and social impairment. Clinical treatment usually has low effectiveness, and surgical resection is frequently indicated. CASE REPORT: We report a case of a male-to-female transgender patient who was referred for treatment of chronic genital lymphedema. She had a history of pelvic radiotherapy to treat anal cancer and of liquid silicone injections to the buttock and thigh regions for esthetic purposes. Radiological examinations showed signs both of tissue infiltration by liquid silicone and of granulomas, lymphadenopathy and lymphedema. Surgical treatment was performed on the area affected, in which lymphedematous tissue was excised from the scrotum while preserving the penis and testicles, with satisfactory results. Histopathological examination showed alterations compatible with tissue infiltration by exogenous material, along with chronic lymphedema. CONCLUSION: Genital lymphedema may be caused by an association of lesions due to liquid silicone injections and radiotherapy in the pelvic region. Cancer treatment decisions for patients who previously underwent liquid silicone injection should take this information into account, since it may represent a risk factor for radiotherapy complications.

(99m) T c-DTPA Study to Validate an Experimental Model of Ureteral Obstruction in Rabbits: Preliminary Results.

Objective. To create a ureteral obstruction experimental model that can be proved through 99mTc-DTPA renal scintigraphy and histopathological studies, without causing total renal function loss. Materials and Methods. Ten New Zealand white rabbits were submitted to a surgical experiment to create a model of unilateral obstruction to urinary flow. Surgery procedure provided unilateral ureteral obstruction (left kidney) to urinary flow and posteriorly was evaluated by 99mTc-DTPA renal scintigraphy and histopathological study. 99mTc-DTPA renal study was performed to detect and quantify signs of obstruction and to evaluate renal function. Statistical analysis was performed through the Student t-test with a significance level of P<0.05. Results. Nine of the ten rabbits presented left renal unit obstruction and one nonobstructive on the 99mTc-DTPA and histopathological studies. All the right renal units, which were not submitted to surgical procedure, were nonobstructed by the studies. There was a general agreement between scintigraphy and histopathological results in both groups. Conclusion. The experimental model promoted the creation of ureteral obstruction in rabbits, confirmed by nuclear medicine scintigraphy and histopathology, and could be used in further studies to better understand urinary obstruction.