Giorgio Mazzon

Immunohistochemical evaluation of androgen receptor and nerve structure density in human prepuce from patients with persistent sexual side effects after finasteride use for androgenetic alopecia

Finasteride is an inhibitor of 5-α-reductase used against male androgenetic alopecia (AGA). Reported side effects of finasteride comprise sexual dysfunction including erectile dysfunction, male infertility, and loss of libido. Recently these effects were described as persistent in some subjects. Molecular events inducing persistent adverse sexual symptoms are unexplored. This study was designed as a retrospective case-control study to assess if androgen receptor (AR) and nerve density in foreskin prepuce specimens were associated with persistent sexual side effects including loss of sensitivity in the genital area due to former finasteride use against AGA. Cases were 8 males (aged 29–43 years) reporting sexual side effects including loss of penis sensitivity over 6 months after discontinuation of finasteride who were interviewed and clinically visited. After informed consent they were invited to undergo a small excision of skin from prepuce. Controls were 11 otherwise healthy matched men (aged 23–49 years) who undergone circumcision for phimosis, and who never took finasteride or analogues. Differences in AR expression and nerve density in different portions of dermal prepuce were evaluated in the 2 groups. Density of nuclear AR in stromal and epithelial cells was higher in cases (mean 40.0%, and 80.6% of positive cells, respectively) than controls (mean 23.4%, and 65.0% of positive cells, respectively), P = 0.023 and P = 0.043, respectively. Conversely, percentage of vessel smooth muscle cells positive for AR and density of nerves were similar in the 2 groups. The ratio of AR positive stromal cells % to serum testosterone concentrations was 2-fold higher in cases than in controls (P = 0.001). Our findings revealed that modulation of local AR levels might be implicated in long-term side effects of finasteride use. This provides the first evidence of a molecular objective difference between patients with long-term adverse sexual effects after finasteride use versus drug untreated healthy controls in certain tissues.

Role of US in acute scrotal pain

BackgroundThe acute scrotum is a common emergency department (ED) presentation and can be defined as any condition of the scrotum or intrascrotal contents requiring emergent medical or surgical intervention. Although rarely fatal, acute scrotal pathology can result in testicle infarction and necrosis, testicular atrophy, infertility, and significant morbidity.MethodsScrotal US is best performed with a linear 7.5- to 12-MHz transducer. In addition to imaging in the longitudinal and transverse planes, it is helpful to obtain simultaneous images of both testes for comparison. Color Doppler is used to evaluate for abnormalities of flow and to differentiate vascular from nonvascular lesions. Attention to appropriate color Doppler settings to optimize detection of slow flow is critical.ResultsThe evaluation of acute scrotal pain can be challenging for the clinician initially examining and triaging the patient. Acute scrotal conditions due to traumatic, infectious, vascular, or neoplastic etiologies can all present with pain as the initial complaint. Additionally, the laboratory and physical examination findings in such conditions may overlap; this, coupled with potential patient guarding and lack of collaboration, may result in a limited, non-specific physical examination. Therefore, scrotal ultrasound has emerged to play a central role in the evaluation of the patient presenting with acute scrotal pain.ConclusionsIn conclusion, we are firmly convinced that a scrotal ultrasound should always be performed in the presence of acute scrotal pain. Moreover, urologist should be able to perform a scrotal ultrasound but, if imaging does not supply a clear diagnosis, surgical exploration is still mandatory.

A pharmacogenetic survey of androgen receptor (CAG)n and (GGN)n polymorphisms in patients experiencing long term side effects after finasteride discontinuation

Finasteride is a steroid 5-alpha-reductase inhibitor, approved for the treatment of androgenetic alopecia (AGA) and benign prostate hyperplasia. In some patients the treatment is associated with adverse side effects that could become persistent after therapy discontinuation, resulting in the so-called post-finasteride syndrome (PFS). A pharmacogenetic component in the response to finasteride treatment was previously demonstrated. Two polymorphisms (CAG) rs4045402 and (GGN) rs3138869 in the gene encoding for the androgen receptor (AR) have been hypothesized to play a role in finasteride sensitivity. We aimed to compare the rs4045402 and rs3138869 polymorphisms prevalence in a group of 69 selected subjects (AGA+PFS) that used finasteride to treat alopecia and developed persistent side effects, with that in a group of 91 untreated subjects with AGA (AGA), and a group of 76 untreated subjects without AGA (NO-AGA). The rs4045402 and rs3138869 polymorphisms extreme-lengths alleles were more frequent among AGA+PFS (odds ratio, 5.88; 95% CI, 1.87-18.52) and AGA subjects (odds ratio, 3.55; 95% CI, 1.13-11.21) than among NO-AGA subjects, probably reflecting the genetic predisposing factors for AGA development. In conclusion, we described a predictive effect of the less common repeats’ length CAG-rs4045402 and GGN-rs3138869 on AGA development. Prospective trials are required to confirm our findings also in other ethnicities, and to highlight possible further pharmacogenetic predictive markers of susceptibility to adverse effects.

Neovaginal prolapse in male-to-female transsexuals: an 18-year-long experience.

Neovaginal prolapse is a rare and distressing complication after male-to-female sexual reassignment surgery. We retrospectively analysed the prevalence of partial and total neo-vaginal prolapses after sexual reassignment surgery in our institute. During the years, two different techniques have been adopted with the aim of fixing the neovaginal cylinder. In the first, two absorbable sutures are placed at the top of the penoscrotal cylinder and fixed to the Denonvilliers fascia. In the second, two additional sutures are added from the posterior/midpoint of the flap to the prerectal fascia. We enrolled 282 consecutive transsexual patients. 65 (23.04%) out of the 282 were treated with the first technique and the following 217 (76.96%) with the last technique. In the first technique, 1 case (1.53%) of total prolapse and 7 cases (10.76%) of partial prolapse were observed, while in the other 217 patients treated with the second technique only 9 cases of partial prolapse were observed (4.14%) and no cases of total prolapse. All prolapses occurred within 6 months from the procedure. In our experience, the use of 4 stitches and a more proximal positioning of the sutures to fix the penoscrotal apex with the Denonvilliers fascia guarantees a lower risk of prolapse.

Varicocele treatment: A 2-centers comparison between non microsurgical open correction, laparoscopic approach and retrograde percutaneous sclerotization on 463 cases

OBJECTIVES To determine whether there are differences in sperm parameters improvement after different varicocele correction techniques. To determine the role of age in sperm parameters improvement. METHODS 2 different European centers collected pre- and postoperative sperm parameters of patients undergoing varicocele correction. Among 463 evaluated patients, 367 were included. Patients were divided in procedure-related and age-related groups. Ivanissevich inguinal open surgical procedure (OS), lymphatic-sparing laparoscopic approach (LSL) and retrograde percutaneous transfemoral sclerotization (RPS) were performed. As outcome measurements sperm count (millions/mL, SC) and percentage of mobile sperms were analyzed. Univariate and multivariate regression between the defined groups; bivariate regression analysis between age and sperm count and motility. RESULTS Number of patients: OS 78; LSL 85; RPS 204. Mean age 30.2 (SD 6.83); postoperative SC increased from 18.2 to 30.1 (CI 95% 27.3-32.9; p < 0,001); motility from 25.6 to 32.56% (30.9-34.2; p < 0.001). OS: SC varied from 16.9 to 18.2 (p < 0.001); sperm motility from 29% to 33% (p < 0.001). LSL: SC from 15.5 to 17.2 (p < 0.001); motility from 27 to 31% (p < 0.001). RPS: SC from 18.9 to 36.2 (p < 0.001); motility from 24% to 32% (p < 0.001). Univariate and multivariate analysis confirmed the significant difference of SC variation in RPS, compared to the other groups (p < 0.001). No significance between LSL and OS (p = 0.826). No significant differences regarding motility (p = 0.8). CONCLUSIONS Varicocele correction is confirmed useful in improving sperm parameters; sclerotization technique leads to a better sperm improvement compared to other studied procedures; improvement in seminal parameters is not affected by age of the patients treated.

Anatomy of the Scrotum

An adequate knowledge of normal anatomy of the scrotum and its content is mandatory to identify the structures during imaging evaluation, and to understand their modifications when pathologies occur. In this chapter anatomy of the scrotal wall, testis, and cord will be described with particular emphasis to the structures that are clinically relevant and can be better recognized at ultrasound and other imaging modalities.

Surgical Therapy: Forearm Free Flap Phalloplasty

Since its first description more than 20 years ago, phalloplasty using a free sensate flap is commonly considered as the gold standard for phallic reconstruction in female-to-male (FTM) transsexuals. Surgeons performing this procedure have to face different patient’s needs, including a good cosmetic result, a good rigidity, a tactile sensitivity and voiding while standing. The procedure may include the reconstruction of the urethra. Different techniques have been adopted during decades. Free flaps from nearly all parts of the body were described for penile reconstruction, but after an initial and euphoric phase, more recent publications of larger series of patients revealed a restriction to only two favourite donor sites: forearm flaps and fibula flaps.

It's not always varicocele: A strange case of Zinner syndrome

A 42-year-old man presented with a huge varicocele. The patient was completely asymptomatic and he did not complain of dysuria, perineal discomfort, or ejaculatory pain. During the visit, the mass mimicked a varicocele and during the Valsalva maneuver a reflux was documented by colour Doppler ultrasound and an abdominal ultrasound revealed an agenesis of the right kidney and a 4.5-cm diameter intra-prostatic cyst. An abdominal and pelvis magnetic resonance imaging was then performed, which confirmed the right renal agenesis, with an epididymal enlargement in the body and tail. This is a unique case of Zinner syndrome in which the patient presented with a paratesticular mass mimicking a varicocele.

MP22-19 PERI-OPERATIVE OUTCOMES OF PERCUTANEOUS STONE SURGERY IN PATIENTS WITH URINARY DIVERSIONS.

volume (V) of each stone, calculated by a special software of CT or by approximation calculation by urologists. After insertion of a ureteral access sheath, Videoscope (FlexXC Storz, Germany) was introduced into the sheath manually. Then the scope was connected to the Roboflex in sterile condition and the time for this procedure had been recorded. Ergonomic chair of Roboflex can be adjusted in a comfortable position, according to the user. Deflection can be performed by manipulating the right handle similar to standart fURS. Precise deflection provided from the thumb wheel on the console. The rotation and forward and backward movement can be controlled by left handle. Fragments smaller than four fold of the laser fiber (means approx. 1 mm) were left for spontaneous passage. The fragmentation time recorded and the Fragmented Volume /per minute was calculated. At the end of the procedures, ureteral j stents were placed whenever indicated. RESULTS: Mean Stone Volume was 1620 cubic mm (98-10600 cubic mm). Mean connection time to the Roboflex was 2 min. Stones were located in upper, middle and lower calices, and renal pelvis. Fragmentation Efficiency (FE) evaluated by fragmentation volume/per minute was 36 and 25 cubic mm /min for manual and robotic fURS respectively, but it increased to 33 cubic mm/min after 42 case. With some improvements of Roboflex FE was increased to 53 cubic mm/min. Stone-free status including fragments up to 2mm as controlled with xray on day 1 was achieved in all cases. We analyzed the CT controls after 1st and 3rd months. Fever not exceeding one day was seen in 2 patients. CONCLUSIONS: Robot assisted fURS using Roboflex has been detected as a safe and efficient treatment method. It offers performing the procedure out of radiation exposure area while sitting. The operative results are also acceptable compared to the literature of manual fURS stone treatment.

Clinical Evaluation of Scrotal Disease

The basic approach to the urological patient is still dependent on taking a complete history and an appropriate physical examination. A well-taken history frequently is sufficient to determine the correct diagnosis. Symptoms which have to be researched with attention are, in particular, pain, and sexual dysfunction. Physical examination should be performed conscientiously. Complete evaluation requires inspection of the breast, testis, vas deferens, and epididymis. In this chapter, those urologic symptoms and clinical signs which are apt to be brought to the physician’s attention would be discussed.