Gaetano Gulino

Extracorporeal shockwave lithotripsy in pediatrics

Since its introduction in 1980, extracorporeal shockwave lithotripsy (SWL) has become the first therapeutic option in most cases of upper-tract urolithiasis, and the technique has been used for pediatric renal stones since the first report of success in 1986. Lithotripter effectiveness depends on the power expressed at the focal point. Closely correlated with the power is the pain produced by the shockwaves. By reducing the dimensions of the focus, it becomes possible to treat the patient without anesthesia or analgesia but at the cost of a higher re-treatment rate. Older children often tolerate SWL under intravenous sedation, and minimal anesthesia is applicable for most patients treated with second- and third-generation lithotripters. Ureteral stenting before SWL has been controversial. Current data suggest that preoperative stent placement should be reserved for a few specific cases. Stone-free rates in pediatric SWL exceed 70% at 3 months, with the rate reaching 100% in many series. Even the low-birth-weight infant can be treated with a stone-free as high as 100%. How can one explain the good results? Possible explanations include the lesser length of the childs ureter, which partially compensates for the narrower lumen. Moreover, the pediatric ureter is more elastic and distensible, which facilitates passage of stone fragments and prevents impaction. Another factor is shockwave reproduction in the body: there is a 10% to 20% damping of shockwave energy as it travels through 6 cm of body tissue, so the small body volume of the child allows the shockwaves to be transmitted with little loss of energy. There are several concerns regarding the possible detrimental effect of shockwaves on growing kidneys. Various renal injures have been documented with all type of lithotripters. On the other hand, several studies have not shown adverse effects. In general, SWL is considered to be the method of choice for managing the majority of urinary stones in children of all ages. Re-treatments improve the stone-free rate, often raising it to 100%. Among the predictors of success, stone size seems to be the most important. In the absence of guidelines, selecting the appropriate treatment modality for each child requires planning and depends on instrument availability and local expertise.

Efficacy of an assisted low-intensity programme of perioperative pelvic floor muscle training in improving the recovery of continence after radical prostatectomy: a randomized controlled trial

Study Type – Therapy (RCT)

Imaging in prostate cancer diagnosis: present role and future perspectives

Prostate cancer (PCa) remains a major health concern for the male population. Detection and primary diagnosis of PCa are based on digital rectal examination, serum prostate-specific antigen levels, and transrectal ultrasound (TRUS)-guided random biopsy. Moreover, the gold standard for detecting PCa, systematic biopsy, lacks sensitivity as well as grading accuracy. This review summarizes recent developments of ultrasonography modalities and functional magnetic resonance imaging (MRI) in the diagnosis of PCa. A comparison between the different methods is presented, including their clinical value and usefulness. It is concluded that innovative ultrasound techniques (including ultrasound contrast agents, 3-D and 4-D sonography, elastography and harmonic sonography) promise benefits in comparison to standard TRUS to accurately diagnose PCa. Promising advances have been made in the detection of PCa with multiparametric MRI. The combination of conventional and functional MRI techniques (including diffusion-weighted imaging, dynamic contrast-enhanced MRI, and MR spectroscopy) can provide information for differentiating PCa from noncancerous tissue and can be used for MRI-guided biopsies, especially in patients with persistent elevation of serum prostate-specific antigen and previous negative TRUS-guided biopsies. However, functional MRI technique and MRI-guided biopsy remain expensive and complex tools presenting inherent challenges.

Paraneoplastic Syndromes in Patients with Urological Malignancies

Introduction: Paraneoplastic syndromes (PNS) may represent the main clinical problem in cancer patients; however, the knowledge of their clinical aspect remains quite poor among urologists. Objective: To provide urologists with an overview on main clinical aspects of PNS that have been reported to be associated to urological cancers. Methods: Literature search of peer-reviewed papers published by July 2008. Results: All genitourinary tumors can cause a PNS, and renal cell carcinoma is the most frequent urological malignancy involved. Prostate cancer is the second urological tumor associated with PNS which, conversely, are uncommon in bladder cancer and rare in testicular cancer. Tumor neuroendocrine differentiation is involved in most endocrine PNS. Neurologic PNS are very uncommon but may dominate the clinical picture and need a high suspicion index to be recognized. Important advances have been made on radionuclide scan methods in order to detect the primary tumor. The most effective treatment strategy is always represented by the radical therapy of the underlying cancer, but specific therapeutic options are sometimes available. Conclusions: Endocrine PNS are frequently associated with urological cancers, especially renal and prostate carcinoma. PNS have been rarely reported in association with cancers of bladder, urethra and testicle.

Discovery history and clinical development of mirabegron for the treatment of overactive bladder and urinary incontinence

Introduction: Overactive bladder (OAB) and urinary incontinence, although not life-threatening, are very bothersome chronic health conditions. The limitations of current pharmacological treatment urge the need for novel drugs with alternative mechanisms of action. Huge efforts in this area of research led to the synthesis of several selective and potent β3-adrenoceptor agonists that gained relevance through research during the late 80s and 90s. Mirabegron was the first compound of this new class of drugs that showed preclinical efficacy in several models of storage bladder dysfunction, together with a favorable human pharmacological profile. Having passed the proof-of-concept stage, an extensive clinical development and pharmacology program was performed during the last 10 years, involving > 10,000 individuals, before mirabegron was granted marketing approval. Areas covered: In this case history, the authors review the milestones in mirabegrons discovery based on a systematic literature review. Expert opinion: Thanks to its tolerability and safety/efficacy balance, mirabegron has potential to fill a need for new treatment options for OAB, and paves the way for further development of a completely new class of drugs aimed to treat this condition. However, the exact role of mirabegron in clinical practice has yet to be defined. Further studies are needed in order to clarify, together with post-launch information, critical safety issues and cost-effectiveness in head-to-head comparison with current standard treatments.

Imaging of Renal Cell Carcinoma: State of the Art and Recent Advances

Background and Aim: Renal cell carcinoma (RCC) is the 13th most common cancer worldwide and accounts for 4% of all adult malignancies. Herein the state of the art and recent advances in cross-sectional radiological imaging applied to RCC are reviewed, including ultrasonography, computed tomography, magnetic resonance imaging, and positron emission tomography. Methods: Literature search of peer-reviewed papers published by October 2010. Results: In front of more conventional and widespread imaging tools, such as ultrasonography and computed tomography, an array of newer and attractive radiological modalities are under investigation and show promise to improve our ability to noninvasively detect renal tumors and its recurrences, accurately assess the extent of the disease, and reliably evaluate treatment response, particularly in the era of antiangiogenetic therapy. Conclusions: Recent major advances in radiological imaging techniques have considerably improved our ability to diagnose, stage and follow-up RCC. Further studies are needed to evaluate the potential of most recent and still investigational imaging tools.

PATIENT SELECTION CRITERIA IN THE SURGICAL TREATMENT OF VENO-OCCLUSIVE DYSFUNCTION

PURPOSE We evaluated short and long-term results of simple and complex venous surgery in patients with veno-occlusive dysfunction unresponsive to maximum recommended doses of intracavernous alprostadil, who were selected with newly developed diagnostic indicators. MATERIALS AND METHODS A total of 23 impotent men with a mean age of 41 years (range 20 to 50) underwent complex penile venous surgery. Only patients fulfilling at least 3 criteria were included in study. The criteria were mild cavernous leak assessed by cavernosometry (grades 1 and 2), more than 30% cavernous smooth muscle tissue (histomorphometric analysis), normal analogical corpus cavernosum electromyography recordings according to international standards, cavernosal oxygen tension greater than 65 mm. Hg at erection and age younger than 50 years. RESULTS Of 23 patients 17 (74%) had normal erections within a year after surgery, and 5 of them (29%) complained of recurrent erectile dysfunction. At long-term followup 6 of 12 patients had spontaneous erections. CONCLUSIONS Careful selection with advanced diagnostic techniques should be mandatory before performing venous surgery in patients with high degree veno-occlusive dysfunction as the only alternatives are major therapeutical solutions.

Peyronie’s Disease: Lights and Shadows

Peyronie’s disease (PD) is characterized by the onset of fibrous plaque inside the tunica albuginea of the penile corpora cavernosa that can cause pain and bending during the erection, making intercourse difficult or impossible. Evidence of the literature supports the autoimmune etiology of PD and suggests genetic and familiar conditions, penile traumatisms, and a history of genital tract diseases as risk factors, but no definitive conclusions arise about the pathogenesis of the disease. Few randomized trials demonstrated that medical therapies, such as vitamin E, colchicine, potassium aminobenzoate, tamoxifen, and injection therapy with verapamil, can stabilize the acute phase of the disease. Extracorporeal shock wave therapy and iontophoresis cannot be considered first-line or gold standard therapies. Satisfactory results have been published with the Nesbit operation in large series with low-stage disease, whereas plication procedures have shown significant relapse rates. A high incidence of long-term penile retractions has been reported in high-stage disease treated with plaque incision and simple graft insertion. Malleable, soft, or inflatable prostheses combined with graft implantation have given the best results in terms of penile straightening and lengthening and patient satisfaction. In conclusion, the etiopathogenesis of PD is not yet clearly understood, no medical therapy is fully effective, and surgery remains the gold standard in patients with severe deformity and/or erectile dysfunction.

Sexual outcomes after organ potency-sparing surgery and glans reconstruction in patients with penile carcinoma.

Introduction: Radical surgery is the “gold standard” for treatment of invasive penile carcinoma but very poor aesthetic, functional and psychological outcomes have been reported. Our purpose was to assess the impact of organ potency-sparing surgery in locally confined carcinoma of the penis. Materials and Methods: We evaluated retrospectively 42 patients with early penile cancer (Ta,T1,T2), treated with glandulectomy and glanduloplasty with urethral mucosa and sparing of cavernosal apexes, or glandulectomy and limited apical resection in cases of Stage T2. Sexual function, ejaculation and libido were evaluated with an IIEF-15 questionnaire before the appearance of neoplasia (about three months before the surgery) and six months after surgery. Quality of life was evaluated by the Bigelow-Young questionnaire. The scores relating to two weeks prior to the surgery have been compared to those obtained six months after surgery. The statistical analysis was conducted using t-Student for repeated measures and analysis of variance. Results: Six months after surgery 73% of patients reported spontaneous rigid erections, 60% coital activity while 76% of the group treated with urethral glanduloplasty reported normal ejaculation and orgasm, regained an average of 35 days after surgery. The average IIEF-15 scores reported in the entire series in the domains of erection, libido and coital activity of the pre-cancer period were not statistically different than those recorded six months after surgery. In the group treated with glandular reconstruction, pre-and postoperative IIEF-15 mean scores related to ejaculation and orgasm domains were not significantly different. Mean scores of Bigelow-Young questionnaires related to sexual pleasure, familial, social and professional relationships showed significant improvement after surgery. Conclusions: Potency sparing-sparing surgical treatments have a positive impact on a wide spectrum of the patients life including family relationships, and social and working conditions.

Corpus cavernosum electromyography (CC-EMG): A new technique in the diagnostic work-up of impotence

We have studied cavernous electrical activity in 42 subjects, healthy volunteer controls and groups of impotent, patients using a nonspecific electromyographic device (PICO-MENFIS) and a specific one, the SPACE-recorder 7500 designed to achieve electric recordings from the corpora cavernosa. In all of the patients, we detected under basal conditions a mean amplitude of 583±323 μV, a mean duration of 4.9±7 s,a mean polyphasicity of 3.5±1.4. It should be emphasized that a significant reduction of potential amplitudes was recorded after pharmacological stimulation in both the controls and the impotent patients. The healthy controls showed amplitudes significantly higher than the impotent patients after radical cystectomy (715±141 μV versus 381±227 μV, p<0.01).The patients after a “nerve-sparing” radical cystectomy with a mean amplitude similar to the controls (500–700 μV) reacted well to the intracavernous drugs in a high percentage of cases.In our experience, CC-EMG seems to be a reliable method which can pinpoint directly lesions to the cavernous smooth muscle and penile autonomic nerves. It has also been able to assess the effects of stress, anxiety and pain on the erectile mechanisms.