Giovanni Caruana

Safety and tolerability of local treatment with iloprost, a prostacyclin analogue, in patients with Peyronie's disease: a phase I study

Study Type – Therapy (case series)

Sexual dysfunctions after transurethral resection of the prostate (TURP): Evidence from a retrospective study on 264 patients

OBJECTIVES Benign prostatic hyperplasia (BPH) and sexual dysfunctions are diseases with a high prevalence in aged men. Several studies have found a link between BPH and LUTS resulting from deterioration in sexual function in men aged 50 years and older for whom TURP is considered the gold standard. The impact of TURP on sexual functions still remain uncertain, nor is it clear what pathophysiological mechanism underlying the emergence of new episodes of Erectile Dysfunction (ED) following TURP in patients with normal sexual function before surgery, while retrograde ejaculation and ejaculate volume reduction represent a clear side effect; derived from BPH treatment. The aim of this study was to retrospectively evaluate the effects of transurethral resection of the prostate (TURP) on sexual function in patients operated in the period 2008-2012 at the Department of Urology of the University Hospital P. Giaccone, and at Villa Sofia-Cervello Hospital- Palermo. Secondary objective was to reconnect the sample data to interventional practice and international standards. MATERIALS AND METHODS The retrospective longitudinal study was conducted on 264 of the 287 recruitable patients, aged between 50 and 85 years, suffering from BPH who underwent to TURP in the period 2008-2012. Telephone interviews were conducted and the International Index of Erectile Function (IIEF) was administered to assess sexual function. Patients enrolled were asked to respond to the test by referring at first to their sexual status in the period before surgery and subsequently to the state of their sexual function after treatment so as to obtain, for each patient, a pre- and post-TURP questionnaire in order to get comparisons that corresponding to reality and to avoid overestimation of the dysfunctional phenomenon. RESULTS In the pre-TURP, the 94.32% of the sample reported being sexually active, with good erectile function in 41.3% of cases, ED mild/moderate in 51.5% and complete ED in 1, 5% of cases; good libido in 62.9% of cases, lack of libido in 31.4% of cases and absent in 5.7% of cases (the latter data corresponded to patients not sexually active); to be sexually satisfied in 29.5% of cases, slightly dissatisfied in 11, 7% of cases, moderately in 35.3% of cases, dissatisfied and very dissatisfied in 23.5% of cases (of which 17.8% sexually active and 5.7% non-active). In the post-TURP 89.4% of the sample reported being sexually active, with good erectile function in 39.1% of cases, DE mild/moderate in 46.9% and complete DE in 4% of cases; good libido in 53.8% of cases, lack of libido in 33.7% of cases and absent in 13.5% of cases (including 1.9% of sexually active and 10.6% of non-active); to be sexually satisfied in 29.5% of cases, slightly dissatisfied in 9.5% of cases, moderately in 35.3% of cases, dissatisfied and very dissatisfied in 17.8% of cases (of which 14.8% sexually active and 10.6% inactive). Retrograde ejaculation was referred in 47.8% of those sexually active after TURP (42.8% if we consider the whole sample). CONCLUSIONS TURP had no negative impact on erectile function in contrast to ejaculatory function. Of the 109 patients with good erectile function in pre-TURP, 5.8% reported a worsening of erectile function after TURP. Among the 136 patients with ED moderate/mild pre-TURP 3.7% reported a worsening in the post-TURP, 16.2% reported an improvement, while 9.5% stopped any sexual activity. In 3.7% of the cases a complete ED was reported after TURP, while a decline of libido and sexual satisfaction was detected in all patients with worsening of sexual function. Retrograde ejaculation was observed in 48% of those sexually active after TURP. Particular attention has to be paid to the psychological aspects, both before surgery and in the postoperative period, which may become an important factor in the decline of sexual activity.

Cytokine gene expression in the tunica albuginea of patients with Peyronie’s disease. Pilot study with a control group

Introduction and objective Cytokines may be involved in the pathogenesis of Peyronies disease (PD). In this case, biological drugs, acting on specific cytokines, could be adopted in the pharmacological treatment of the disease. Materials and Methods Twenty PD patients and 8 patients affected by congenital recurvatum penis (control group) who underwent corporoplasty were enrolled in the study Histological examination and measurement by Real Time PCR of the expression of the encoding genes for IL-2, IL-4, IL-6, IL-10, IL-13, TGF-β, TNF-α and IFN-γ were performed on the removed tunica albuginea (TA). For the normalization of data GAPDH (glucerldehyde-3fosfatehydrogenase) and GUSB (β-glucuronidase), housekeeping genes were used. The analysis of the data was performed using the comparative method of ΔCt. The results were reported with the Fold of induction (FOI) method. Results The histological exams of TA showed only fibrous tissue without cavernous tissue. The analysis of gene expression of IL-6, IL-10, IFN-γ and TGF-β1 showed in all samples very low levels. The levels were lower in PD patients although the differences were not statistically significant. An exception was represented by TGF-β that showed a higher level in PD patients, although not statistically significant. The expression of IL-4, IL-13 and TNF-α was undetectable. Conclusions The expressions of cytokines in TA of PD patients compared to those of the controls do not show any significant difference. A bias of our study is that the groups were not age-matched. This is a bias already present in similar experiences and due to the different pathogenesis of the diseases. Cytokines promoting inflammation resulted undetectable and do not seem to be involved in PD pathogenesis. The higher level of TGF-β, a pro-fibrotic cytokine, detected in PD could explain the presence of fibrotic tissue. Presently, there is no data suggesting a possible role of biological drugs in PD.

Mitomycin C from birth to adulthood.

Mitomycin C (MMC) intravesical therapy for “superficial” papillary bladder tumors was firstly introduced in the early seventies with promising results. In the following years, several pharmacokinetic studies investigated its mechanism of action to optimize the intravesical administration. Numerous studies confirmed thereafter both the ablative and the prophylactic efficacy and the low toxicity of MMC when intravesically given. In 1984, a complete response rate of 42% in 60 patients not responsive to thiotepa was reported with intravesical MMC at the dose of 40 mg diluted in 40 ml for 8 weeks. In the following decades, many large randomized studies showed the benefit of intravesical prophylaxis with MMC versus transurethral resection (TUR) alone. Since 2002, the role of adjuvant intravesical chemotherapy and of an early MMC instillation in preventing recurrence compared with TUR alone has been confirmed by large meta-analyses and stated by the European Association of Urology (EAU) guidelines. The need for further intravesical chemotherapy after the early instillation in patients at intermediate-high risk of recurrence has been proved by several trials. Although intravesical Bacillus Calmette-Guerìn (BCG) is considered the best choice for high-risk patients and MMC for the low-risk group, both MMC and BCG can be given to prevent recurrence in intermediate-risk patients. However, the higher efficacy of BCG over MMC is evident only if maintenance regimen is administered. Despite its proven efficacy, immediate intravesical MMC is not yet fully entered in common clinical practice and efforts should be made by the urologists to optimize its adoption.

The clinical value of PSA increase during intravesical adjuvant therapy for nonmuscle-invasive bladder cancer

Introduction Prostatic Specific Antigen (PSA), Bacillus Calmette-Guerin (BCG) increase after intravesical BCG has been reported. The need of prostate biopsy in these patients is object of debate. The aim of our study was to evaluate the effect of intravesical therapy on PSA after transurethral resection (TUR) of nonmuscle-invasive bladder cancer (NMIBC). Materials and methods Patients undergoing intravesical chemotherapy or immunotherapy for NMIBC were entered. PSA was measured before TUR, before the first and after the sixth instillation, 30 and 90 days after the last instillation. Patients with PSA ≥4 ng/ml or palpable prostate nodule were excluded. Results Out of 130 patients, 105 were evaluable. PSA increase (mean: 7.15 ng/ml) was detected after TUR and before intravesical therapy in 14 patients (13.3%). Of the remaining 91 patients, 65 (71.4%) received chemotherapy and 26 (28.6%) BCG. Median PSA before and during therapy was 1.80 and 1.97 ng/ml, with a 36% median increase in 66 patients (72.5%) (p = 0.13). No statistically significant difference emerged between chemotherapy and BCG (p = 0.22). PSA higher than 4 ng/ml was detected in six (6.3%) and two (2.1%) patients after chemotherapy and BCG, respectively, and was no more evident at 90 days. Discussion PSA increase due to intravesical therapy is rare and usually not clinically significant. PSA rising above 4 ng/ml during intravesical treatment was evident only in 8% of patients. PSA before TUR should be available and considered as the basal value. Elevated PSA detected during therapy should be monitored and biopsy proposed only if persisting more than 3 months after the end.

Compliance to therapy with Dapoxetine in patients affected by Premature Ejaculation

Introduction Premature ejaculation (PE) is a sexual dysfunction with high prevalence. According to some reports, it is present in about 20-30% of the male population. Since 2009 PE has been treated with a novel inhibitor of serotonin re-uptake, Dapoxetine, which has been reported to be specifically active for PE. Materials and Methods 59 patients have been selected among the patients affected by PE observed at the outpatient department of Urology and Andrology of the “Paolo Giaccone” University Policlinic Hospital of Palermo. Diagnosis was confirmed unequivocally in all patients, who were suitable for drug treatment and accepted to participate in the study. They were divided in 2 groups: one receiving Dapoxetine (41 patients), another (18 patients) receiving Citalopram. Patients were followed up by telephone at monthly intervals, in order to compare compliance, efficacy and side effects. Results Compliance to treatment was obtained in 56% of patients treated with Dapoxetine and in 61% of those treated with Citalopram. In the Dapoxetine group side effects were reported in 14.6% versus 38.4% in the Citalopram group. Benefit from the treatment was reported in 82% and 69.2%, respectively.

Evidence of intimal tear in type A intramural hematoma of the aorta: A case series

Highlights • We report two cases of type A intramural hematoma of the aorta.• We found radiological and intraoperative evidence of an intimal tear.• This finding supports the hypotesis that IMH belong to “aortic dissection” disease.

The “serpent sign” in hydatid disease

The ‘‘serpent sign’’ is a radiological finding of Echinococcus infections and refers to discrete, curvilinear structures found within a complex hydatid cyst [1]. These structures represent the laminated membranes of the endocyst detached from the pericyst, resulting in intracystic floating membranes that mimic the appearance of a serpent (Fig. 1). The typical hydatid cyst is composed of three layers:

The “caput medusae” sign in portal hypertension

The ‘‘caput medusae’’ sign is a clinical and radiological finding, which can be detected in patients with severe portal hypertension. It describes engorged paraumbilical veins radiating from the umbilicus within the adipose tissue of the anterior abdominal wall, creating portosystemic anastomoses [1]. This sign takes its name from Medusa, the mythological gorgon of Greek mythology, generally described as a winged human female with living venomous snakes in place of hair (Fig. 1). She instantly turned anyone to stone who looked upon her hideous face, until she was beheaded by the hero Perseus, who used her severed head as a weapon, literally petrifying his enemy [2]. The ‘‘caput medusae’’ sign results from reopening of paraumbilical veins that shunt blood from portal vein into systemic circulation (mainly through connections with epigastric veins). Paraumbilical veins appear as multiple serpentine structures, usually remaining asymptomatic, so that they may be discovered incidentally on abdominal imaging performed in cirrhotic patients [1]. However, several cases of hemorrhage from recanalized paraumbilical veins were described in literature [3]. The ‘‘caput medusae’’ sign is most commonly detected during clinical examination of patients with advanced cirrhosis. However, tortuous collaterals around the umbilicus can be classically described on abdominal ultrasound, CT or MRI during evaluation of patients with portal hypertension of any origin (Fig. 2) [1, 4].

The “bouquet of flowers” appearance in medullary sponge kidney

The ‘‘bouquet of flowers’’ appearance is a radiological finding described for the intravenous pyelography (IVP) diagnosis of medullary sponge kidney (MSK). It refers to contrast pooling in dilated tubular structures in renal papillae, giving a striated pattern to the renal medulla, which resembles a ‘‘bouquet of flowers’’ (Fig. 1) [1]. MSK is an uncommon congenital condition, which occurs in about 0.5-1% of the general population and 8.5% of patients with nephrolithiasis, characterized by cystic dilation of the terminal collecting ducts in renal pyramids, resulting in a sponge-like appearance of the medulla [2]. It may affect one or both kidneys, usually remaining asymptomatic, so that its finding is incidental on abdominal imaging performed for other indications [3]. However, MSK is also known to represent a risk factor for urinary tract infections, hematuria, nephrolithiasis, nephrocalcinosis, and renal acidification defects [2]. Congenital disorders associated with MSK include Ehlers–Danlos syndrome, Caroli’s disease, and Beckwith–Wiedemann syndrome [1]. Traditionally, IVP was widely used for the diagnosis of MSK, and it has generally been considered the gold standard imaging technique, due to its higher spatial resolution for papillary/calyceal detail compared with single-slice CT imaging. Nowadays, multidetector CT urography, combined with 3D reconstructions of images obtained during the excretory phase (Fig. 2), provide