Salvatore Sansalone

The Role of Intrinsic Pathway in Apoptosis Activation and Progression in Peyronie's Disease

Peyronies disease (PD) is characterized with formation of fibrous plaques which result in penile deformity, pain, and erectile dysfunction. The aim of this study was to investigate the activation of the intrinsic apoptotic pathway in plaques from PD patients. Tunica albuginea from either PD or control patients was assessed for the expression of bax, bcl-2 and caspases 9 and 3 using immunohistochemistry and by measurement of apoptotic cells using TUNEL assay. Bax overexpression was observed in metaplastic bone tissue, in fibroblasts, and in myofibroblast of plaques from PD patients. Little or no bcl-2 immunostaining was detected in samples from either patients or controls. Caspase 3 immunostaining was very strong in fibrous tissue, in metaplasic bone osteocytes, and in primary ossification center osteoblasts. Moderate caspase 9 immunostaining was seen in fibrous cells plaques and in osteocytes and osteoblasts of primary ossification centers from PD patients. Control samples were negative for caspase 9 immunostaining. In PD patients the TUNEL immunoassay showed intense immunostaining of fibroblasts and myofibroblasts, the absence of apoptotic cells in metaplasic bone tissue and on the border between fibrous and metaplastic bone tissue. Apoptosis occurs in stabilized PD plaques and is partly induced by the intrinsic pathway.

One-sided anterior urethroplasty: a new dorsal onlay graft technique.

To investigate the feasibility, tolerability, safety and efficacy of using a new surgical technique for the repair of anterior urethral strictures to preserve vascular supply to the urethra and its entire muscular and neurogenic support.

Polyphenols: Key Issues Involved in Chemoprevention of Prostate Cancer

Prostate cancer is is the most common solid neoplasm and it is now recognized as one of the most important medical problems facing the male population. Due to its long latency and its identifiable preneoplastic lesions, prostate cancer is an ideal target tumor for chemoprevention. Different compounds are available and certainly polyphenols represent those with efficacy against prostate cancer. This review take a look at activity and properties of major polyphenolic substances, such as epigallocatechin-3-gallate, curcumin, resveratrol and the flavonoids quercetin and genistein. Although the current studies are limited, mechanisms of action of polyphenols added with the lack of side effects show a a start for future strategies in prostate chemoprevention.

Retrospective Descriptive Analysis of 1,176 Patients With Failed Hypospadias Repair

PURPOSE To our knowledge epidemiological data on the incidence of failed hypospadias repair and the number of patients seeking further surgical treatment remain unknown. We report an observational, descriptive survey of patients who were evaluated and treated for urethral stricture disease and/or penile defects after primary hypospadias repair. MATERIALS AND METHODS We performed a retrospective observational chart analysis of patients evaluated and treated for urethral stricture disease and/or penile defects at 2 tertiary European centers from January 1998 to December 2007. In each case we investigated the primary abnormal meatal site, the number of operations needed to repair primary hypospadias and complications of this primary repair. Patients were offered surgical repair for previous failed hypospadias treatment. After surgery evaluation was scheduled at 3, 6 and 9 months. Success was defined as a functional urethra without fistula, stricture or residual chordee and a cosmetically acceptable glanular meatus after the completion of all secondary procedures. RESULTS A total of 1,176 patients with a mean age of 31 years were evaluated and treated. To treat failed hypospadias repair 760 (64.6%) and 416 patients (35.4%) underwent 1-stage and staged repair, respectively. Mean followup was 60.4 months. Of 1,176 cases 1,036 (88.1%) were classified as successful and 140 (11.9%) were considered failures. CONCLUSIONS Failed hypospadias repair may be corrected by multiple and complex surgeries. Its effects are experienced during the lifetime of the patient and parents.

Ventral oral mucosal onlay graft urethroplasty in nontraumatic bulbar urethral strictures: surgical technique and multivariable analysis of results in 214 patients.

BACKGROUND The ventral oral mucosal onlay graft is suggested in proximal bulbar strictures where the thick spongiosum provides excellent support to the graft. Some technical steps used in this technique are currently under debate in the literature. OBJECTIVE To describe the surgical steps of this urethroplasty and investigate predictive factors of success using a multivariable logistic regression analysis. DESIGN, SETTING, AND PARTICIPANTS This is a descriptive observational retrospective study of 214 patients who underwent urethroplasty for bulbar urethral strictures between May 1999 and November 2010 in a single high-volume center. Study inclusion criteria were patients presenting nontraumatic bulbar urethral strictures ranging from 1.3 cm to 6.8 cm in length. Exclusion criteria were traumatic strictures, panurethral strictures, lichen sclerosus, and failed hypospadias repair. SURGICAL PROCEDURE The oral graft was placed on the ventral bulbar urethral surface and pushed as proximally as possible using dedicated instruments and surgical techniques. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary outcome measure was the objective result, defined as the absence of stricture recurrence at follow-up. The objective outcome was considered a failure when any postoperative instrumentation was needed. Multivariable logistic regression analysis was developed. All tests were two sided with a significance level set at 0.05. RESULTS AND LIMITATIONS Median follow-up was 54 mo. Of the 214 patients, 183 (85.5%) were successful and 31 (14.5%) were failures. The preoperative maximum flow rate (Qmax) was a significant predictor of surgical outcome (odds ratio: 1.352; p = 0.001). Age, length, and type of stenosis, and previous treatment were not significant predictors of surgical outcome (all p > 0.05). The limitation of our survey is the absence of a subjective evaluation or the use of specific tools, such as a questionnaire. CONCLUSIONS Ventral oral graft urethroplasty represents a valid option in nontraumatic bulbar strictures. Preoperative Qmax may be predictive of urethroplasty failure.

A geographic analysis of male urethral stricture aetiology and location.

The incidence of specific aetiologies of urethral stricture disease has been reported from a variety of series throughout the world. Most reported urethral stricture series are from single institutions or from a specific region of the world. We provide a multi‐centred series to compare aetiologic incidence between differing regional populations.

Musculocutaneous latissimus dorsi free transfer flap for total phalloplasty in children.

OBJECTIVE Total phalloplasty is rarely performed in children due to the mutilation involved and the dilemma concerning neophallic size in children. We present a musculocutaneous latissimus dorsi free transfer flap for total phalloplasty in children with difficult psychological problems. MATERIALS AND METHODS Total phalloplasty was performed in eight boys aged between 10 and 15 years. Indications were small penis after failed epispadias repair (4), micropenis (3) and intersexuality (1). A musculocutaneous latissimus dorsi free flap was harvested with thoracodorsal artery, vein and nerve. The flap was transferred to the pubic region and anastomosed to the femoral artery, saphenous vein and ilioinguinal nerve. Two-staged urethroplasty was performed in five patients using buccal mucosa, while in the remaining three a Mitrofanoff channel had been created previously. An inflatable penile prosthesis was implanted in two cases after puberty. RESULTS Follow-up was from 6 to 53 months (mean: 29 months). Penile size varied from 13 to 16 cm in length and from 10 to 12 cm in circumference. No flap necrosis, either partial or total, was noted. The donor site healed acceptably in four cases while in the remaining four moderate scarring occurred. Function of the penile prostheses is satisfactory. Psychological status is significantly improved in all children. CONCLUSION Phalloplasty in childhood is indicated to prevent profound psychological problems related to body dysmorphia. The musculocutaneous latissimus dorsi flap is a possible choice for phalloplasty in children that enables good neophallic size as in adults. We recommend this surgery to be performed before puberty to ensure optimal psychosexual pubertal development.

Prediction of Early and Late Complications after Oral Mucosal Graft Harvesting: Multivariable Analysis from a Cohort of 553 Consecutive Patients

PURPOSE We investigated the early and late complications after oral mucosal graft harvesting, and reported the independent predictors of outcome via multivariable analysis. MATERIALS AND METHODS We performed a retrospective descriptive study of 553 patients from whom an oral mucosa graft was harvested for urethroplasty from single or bilateral cheeks. Patients who underwent oral mucosa harvesting from the lip, the tongue or from the cheek and lip at the same time were excluded from analysis. The oral graft was harvested in an ovoid shape with closure of the wound. Postoperative early and late complications were investigated using a self-administered, nonvalidated, semiquantitative questionnaire. There were 6 questions on early complications, and 13 questions investigated late complications and patient satisfaction. RESULTS Descriptive statistics of categorical variables focused on frequencies and proportions. Univariable and multivariable analyses were used to predict early and late dissatisfaction of patients. Bleeding was reported in 3.4% of patients. Overall 53.2% of patients did not report any pain and 36.3% reported no swelling. Late complications analysis showed that 95.5% of patients declared that the surgical closure of the wound did not cause any difficulty in opening the mouth or problems with smiling (98.2%) and/or dry mouth (95.8%). Overall 98.2% of patients were satisfied with the procedure. Univariable and multivariable analyses revealed that bilateral graft harvesting was the only significant predictor of patient dissatisfaction (OR 2.85, p = 0.01 and OR 2.72, p = 0.02; respectively). CONCLUSIONS Harvesting the oral mucosa ovoid graft from a single cheek with closure of the wound is a safe procedure with high rates of patient satisfaction.

Histological Evidence of Urethral Involvement in Male Patients With Genital Lichen Sclerosus: A Preliminary Report

PURPOSE Using pathological examination we evaluated the involvement of lichen sclerosus in urethral strictures in men. MATERIALS AND METHODS We performed an observational, descriptive, retrospective study of patients treated for genital lichen sclerosus who had at least 1 biopsy positive for lichen sclerosus. Study exclusion criteria were malignant penile lesions, incomplete data on personal charts and biopsies negative for lichen sclerosus. Preoperative evaluation included clinical history, physical examination, urine culture, post-void residual urine measurement, uroflowmetry and urethrography. Biopsies were taken from the foreskin, penile skin, glans, urethral meatus, mucosa of the navicularis, and penile and bulbar urethra to confirm the lichen sclerosus diagnosis and spread of the disease through the urethra. Patients were classified into 5 groups by surgical procedure. RESULTS Included in the study were 99 patients with a median age of 46 years who were diagnosed with genital lichen sclerosus. Of 274 biopsies 234 (85.4%) were positive for lichen sclerosus. Group 1 included 39 patients who underwent circumcision, group 2 included 15 who underwent meatotomy, group 3 included 15 who underwent navicularis urethroplasty, group 4 included 17 who underwent penile urethroplasty and group 5 included 13 who underwent perineal urethrostomy. Lichen sclerosus was documented by histology in the meatus in 91.5% of cases, in the navicularis in 84.4% and in the penile urethra in 70.6%. All biopsies from the bulbar urethra were negative. CONCLUSIONS Involvement of lichen sclerosus through the navicularis and penile urethra was documented. No sign of lichen sclerosus was found in the bulbar urethra.

Penile length and girth restoration in severe Peyronie's disease using circular and longitudinal grafting

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