Matteo Vittori

Complications of Extracorporeal Shock Wave Lithotripsy for Urinary Stones: To Know and to Manage Them–A Review

To identify the possible complications after extracorporeal shock wave lithotripsy (SWL) and to suggest how to manage them, the significant literature concerning SWL treatment and complications was analyzed and reviewed. Complications after SWL are mainly connected to the formation and passage of fragments, infections, the effects on renal and nonrenal tissues, and the effects on kidney function. Each of these complications can be prevented adopting appropriate measures, such as the respect of the contraindications and the recognition and the correction of concomitant diseases or infection, and using the SWL in the most efficient and safe way, tailoring the treatment to the single case. In conclusion, SWL is an efficient and relatively noninvasive treatment for urinary stones. However, as with any other type of therapy, some contraindications and potential complications do exist. The strictness in following the first could really limit the onset and danger of the appearance of others, which however must be fully known so that every possible preventive measure be implemented.

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.

Patient-reported outcomes in men with lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) treated with intraprostatic OnabotulinumtoxinA: 3-month results of a prospective single-armed cohort study

Study Type – Therapy (prospective cohort)

Role of SOCS3 evaluated by immunohistochemical analysis in a cohort of patients affected by prostate cancer: preliminary results

Background Chronic inflammation may play a role in prostate carcinogenesis. Molecular alterations of the Suppressor of Cytokine Signaling (SOCS)-3 can contribute to explain the pleiotropic role of interleukin (IL)-6 in this type of cancer. Recently, the methylation of SOCS3 gene has been demonstrated to cause the non-expression of the protein, being involved in the pathogenesis of prostate cancer (PC) and identifying a subset of aggressive tumors. We evaluated the expression of SOCS3 protein in patients (pt) with bioptically-diagnosed PC by immunohistochemical analysis, which is easier to perform, cheaper and more reproducible compared to DNA analysis. Methods We analyzed the protein expression of SOCS3 by immunohistochemistry in 44 patients (pt) with PC diagnosed after biopsy. Slides were incubated with monoclonal antibody SOCS3 (1E4, 1.5 μg/mL; Abnova, Taiwan). The SOCS3 staining intensity was evaluated by two pathologists (FP and LML) in three different ways: positive (+), negative (-) and weak (+/-). Colonic mucosa was used as positive control. 36/44 patients underwent radical prostatectomy (RP). Results Biopsy Gleason score (Gs) was: <7 in 8 pt, 7 in 33 pt (3 + 4 pattern in 21 pt, 4 + 3 pattern in 12 pt), >7 in 3 pt. 8/8 (100%) pt with Gs <7 and 7/33 (21%) with Gs 7 were SOCS+. 15/33 (45%) pt with Gs 7 and 3/3 (100%) pt with Gs >7 were negative. In 11/33 pt (33%) Gs 7 a weak intensity was found so they were classified as SOCS3 +/-. 25/36 (69%) patients who underwent RP were SOCS3– (15 pt with Gs 7(3 + 4), 7 pt with Gs 7(4 + 3), 3 pt with Gs 8) and 11/36 (30%) SOCS3+ (8 pt with Gs 6 and 3 pt with Gs 7(3 + 4)) (Tab 2). 12/25 (48%) SOCS3– pt had an organ-confined disease (≤pT2), whereas 13/25 (52%) had an extra prostatic neoplasm (5 pT3a (one was N+), 6 pT3b, 1 pT4). All SOCS3+ patients (8/8 (100%)) had an organ-confined disease. 3/3 (100%) SOCS3+/- pt had an extra prostatic neoplasm (>pT2). Conclusions SOCS3– pt turned out to have a more aggressive disease compared with SOCS3+. In particular, also SOCS3+/- patients seemed to have an aggressive behavior. The non-expression of SOCS3 protein may identify PC with more aggressive behavior and can be evaluated with immunohystochemical analysis, which is a relatively easy and cheap procedure in clinical practice. These results, if confirmed by a wider population and a longer follow-up, may encourage the research on the use of this molecular family as a prognostic marker and a target for therapy with demethylating agents.

OnabotulinumtoxinA injection therapy in men with LUTS due to primary bladder‐neck dysfunction: Objective and patient‐reported outcomes

To determine efficacy and safety of OnabotulinumtoxinA (BoNT‐A) injection therapy in medically refractory patients with lower urinary tract symptoms (LUTS) due to primary bladder‐neck dysfunction (PBND).

High-intensity focused ultrasound in prostate cancer: Today's outcomes and tomorrow's perspectives

Abstract High-intensity focused ultrasound (HIFU) is a minimally invasive therapy applied for prostate cancer that capitalizes on the coagulation necrosis that occurs at temperatures greater than 60°C. Owing to a lack of long-term follow-up data the procedure is still considered experimental treatment. As primary therapy, HIFU is indicated in patients aged ≥70 years with clinical organ-confined disease, although it has also been used, with encouraging results, as first line salvage therapy after definitive treatment, and in locally advanced (T3–4) and non-metastatic hormone-resistant prostate cancer. Morbidity associated with this treatment method appears to be low and includes urinary retention (1–9%), urethral stricture (4–14%), incontinence (1–15%), erectile dysfunction (13–53%) and rectourethral fistulae (0–3%). The risk of complications increases with repeated treatments. A few studies have recently been published on HIFU as focal therapy. HIFU technology can be enhanced using means such as ultrasound microbubble contrast agents for assessment of therapy efficacy, magnetic resonance imaging to guide the enhancement of heat rate, and localized drug and gene delivery.

Intraprostatic botulinum toxin type “A” injection in patients with benign prostatic hyperplasia and unsatisfactory response to medical therapy: A randomized, double‐blind, controlled trial using urodynamic evaluation

The injection of botulinum neurotoxin A (BTA) into the prostate represents a minimally invasive treatment in patients with lower urinary tract symptoms (LUTS) associated to benign prostatic hyperplasia (BPH). We evaluated the effectiveness of BTA in treating patients with BPH unresponsive to combined medical therapy (CMT), using urodynamic investigations.

Focal surgery in testis cancer: current state of the art

Radical orchiectomy is the standard treatment of testicular neoplasia causing androgen insufficiency, infertility and psychological stress. Focal surgery allows the preservation of fertility, endocrine function and integrity of the genital anatomy, with preservation of the image of the male body. The EAU guidelines suggest focal surgery in case of synchronous bilateral tumours, metachronous contralateral tumours, tumour in solitary testis with normal pre-operative testosterone levels, when the tumour volume is less than 30% of the testicular volume. There are two focal surgical techniques: tumorectomy and polar resection, followed by biopsies and frozen section of the resection bed. In case of benign tumours, the treatment is often curative. In case of malignancy, carcinoma in situ is frequently found in the surrounding tissues. Adjuvant treatment with chemotherapy or radiotherapy is performed with a fair success rate. These adjuvant treatments reduce or delete the functional benefits achieved by conservative surgery. The evidence of the literature suggests that focal surgery is a valid option for all patients with testicular tumours that are not palpable and small sized, with the advantage of avoiding unnecessary radical orchiectomy in most of cases. Therefore, the selection criteria for focal surgery are the mass size (less than 25 mm) and a safety distance of the tumor from the rete testis, in order to preserve testicular vascularization. A close follow-up with ultrasound, testicular markers and radiological examinations is mandatory in case of germ cell neoplasia treated conservatively in patients with indications for conservative surgery.

99mTc-MAG3 diuretic renography in assessment of obstructive uropathy. The new test F+10sp: a step ahead in the differential diagnosis

Background Dilation of the renal pelvis is a problem Urologists have often to deal with. One of the key aspects is to clear if the dilation is the consequence of an obstruction to the outflow or a simple anatomic variant. Aim of this study was to compare two diuretic renographic procedures, F-15 vs the new procedure F+10SP (Seated Position) in a group of hydronephrotic patients, in order to increase the accuracy in the differential diagnosis between non-obstructive and obstructive dilation. Materials and Methods 34 Patients (14 male, 20 female, 18–71 yrs range), 27 pts having an unilateral hydronephrosis and 7 pts a bilateral hydronephrosis diagnosed by ultrasound, were enclosed in the study. They were subjected to two 99mTc-MAG3 diuretic renography with furosemide consecutively, with different modalities: 1) 40 mg of furosemide were administered IV to patient in supine position 15 minutes before tracer injection (Test F-15, by English); 2) the new procedure: 20 mg of furosemide were administered IV to patient in Seated Position (SP), 10 minutes after tracer injection during dynamic acquisition (Test F+10 SP). The average interval between the two tests was 7 days. Two different physicians analyzed all the tests. The results were classified as: non-obstruction (only F+10SP can distinguish between normal and dilated without obstruction), obstruction, equivocal and not applicable. Results Among the 68 renal units (RU) included in the analysis, the F+10SP test showed normal findings in 21 RU (30,8%), dilation without obstruction in 21 RU (30,8%), obstruction in 25 RU (36.8%) and equivocal result in 1 RU. The F-15 renography showed non-obstructive results in 35 RU (51.5%), obstruction in 20 RU (29.4%) and equivocal findings in 11 RU (16.1%); the test was not applicable in 2 RU (2.9%) due to insufficient renal function. Side effects reported for the F-15 renogram were hypotension in 1 patient, renal colic in 3 patients, bladder filling in 13 patients, disruption because of voiding in 4 patients. No complications were observed during or after the F+10SP renography. The 20 RU diagnosed with obstruction at the F-15 test were considered obstructed also at the F+10SP test. Conclusions The “equivocal” test rate lowered from 16% for the F-15 test to less than 1.5% for the new F+10 SP test. The F+10SP procedure is easy, well tolerated, time saving and seems to be a more reliable tool in assessment of obstructive uropathy in adults.

Positive surgical margins in nephron sparing surgery for renal cell carcinoma

Nephron sparing surgery (NSS) with a minimal tumor-free margin is considered the cornerstone in the contemporary management of renal cell carcinoma (RCC) stage T1. The aim of this study is to review incidence, predictive risk factors, clinical significance and oncologic outcomes of positive surgical margins (PSM) in NSS. English articles published before March 2014 have been searched in MEdliNE databank. PSM are present in 0-7% of patients in all surgical approaches considered. Some predictive factors, such as tumor size, localization, and histology have been identified in the past. Other topics concerning surgical technique and approach are discussed. The majority of patients with PSM do not experience disease recurrence and PSM impact on overall survival and cancer-specific survival seems to be irrelevant. These results lead to more conservative clinical strategies. However, an active surveillance is mandatory for all patients with PSM and especially for those with high risk disease. Generalization of these results is limited by the low level of evidence of available studies. Further efforts are necessary to avoid PSM intraoperatively and to provide prospective information in order to standardize the postoperative management.