Luca Villa

Pelvic/Retroperitoneal Salvage Lymph Node Dissection for Patients Treated With Radical Prostatectomy With Biochemical Recurrence and Nodal Recurrence Detected by [11C]Choline Positron Emission Tomography/Computed Tomography

BACKGROUND The management of patients with clinical recurrence of prostate cancer after radical prostatectomy (RP) remains challenging. OBJECTIVE To determine whether the removal of positive lymph nodes at [11C]choline positron emission tomography/computed tomography (PET/CT) scan may have an impact on the prognosis of patients with biochemical recurrence (BCR) and nodal recurrence after RP. DESIGN, SETTING, AND PARTICIPANTS Prospective analysis of 72 patients affected by BCR after RP associated with a nodal pathologic [11C]choline PET/CT scan. INTERVENTION Patients underwent salvage lymph node dissection (LND). MEASUREMENTS Biochemical response (BR) to treatment was defined as prostate-specific antigen (PSA) <0.2 ng/ml at 40 d after salvage LND. Kaplan-Meier and Cox regression analyses addressed time to and predictors of clinical recurrence (CR) after salvage LND, respectively. RESULTS AND LIMITATIONS Overall, 56.9% of patients achieved BR. Mean and median follow-up after LND were 39.4 and 39.8 mo, respectively. The 5-yr BCR-free survival rate was 19%. Preoperative PSA <4 ng/ml (hazard ratio [HR]: 0.12; p = 0.005), time to BCR <24 mo (HR: 7.52; p = 0.005), and negative lymph nodes at previous RP (HR: 0.19; p=0.04) represented independent predictors of BR. Overall, 5-yr CR-free and cancer-specific survival were 34% and 75%, respectively. At multivariable analyses, only PSA >4 ng/ml (HR: 2.13; p=0.03) and the presence of retroperitoneal uptake at PET/CT scan (HR=2.92; p=0.004) represented independent preoperative predictors of CR. Similarly, the presence of pathologic nodes in the retroperitoneum (HR: 2.78; p=0.02), higher number of positive lymph nodes (HR: 1.04; p=0.006), and complete BR to salvage LND (HR: 0.31; p=0.002) represented postoperative independent predictors of CR. Main limitations consisted of the lack of a control group and the heterogeneity of patients included in the analyses. CONCLUSIONS Salvage LND is feasible in patients with BCR after RP and nodal pathologic uptake at [11C]choline PET/CT scan. Biochemical response after surgery can be achieved in a consistent proportion of patients. Although most patients invariably progressed to BCR after surgery at longer follow-up, 35% of patients showed the absence of CR at 5 yr.

Current Standard Technique for Modern Flexible Ureteroscopy: Tips and Tricks

BACKGROUND Thanks to advancements in the endoscopic armamentarium, flexible ureteroscopy (fURS) has become a viable and attractive option for the treatment of renal stones because of its high stone-free rates (SFRs) and low morbidity. OBJECTIVE To describe our surgical technique for fURS, step-by-step, for the treatment of renal stones and to assess its effectiveness and safety. DESIGN, SETTING, AND PARTICIPANTS A retrospective analysis of 316 consecutive patients who underwent fURS for renal stones at our institution between March 2014 and September 2015 was performed. SURGICAL PROCEDURE Ureteroscopy and laser lithotripsy using a standardized technique with last-generation flexible ureteroscopes. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Clinical data were collected in a dedicated database. Intraoperative and postoperative outcomes were assessed. A descriptive statistical analysis was performed. RESULTS AND LIMITATIONS The mean overall stone size was 16.5 ± 7.9mm. Ureteral access sheath placement was possible in 287 patients (90.8%). At 1-mo follow-up, the overall primary SFR was 79.1%; the secondary and tertiary SFRs were 89.5% and 91.5%, respectively. The mean operative time was 72.6 ± 27.5min. The mean number of procedures was 1.27. Complications were reported in 92 patients (29.1%) overall, with Clavien grade 1 in 55 patients (17.4%), grade 2 in 30 patients (9.5%), grade 3 in 6 patients (1.9%), grade 4 in 1 patient (0.3%), and grade 5 in none. The main limitation of the study was the retrospective nature. CONCLUSIONS The fURS procedure is safe and effective for the treatment of renal stones. A staged procedure is necessary to achieve stone-free status with large calculi. PATIENT SUMMARY Flexible ureteroscopy is an effective treatment with low complication rates for the majority of renal stones. Both the modern highly technological armamentarium and surgical know-how should be available.

Kidney stone analysis: "Give me your stone, I will tell you who you are!".

IntroductionStone analysis is an important part in the evaluation of patients having stone disease. This could orientate the physician toward particular etiologies.Material and methodsChemical and physical methods are both used for analysis. Unfortunately, chemical methods often are inadequate to analyze accurately urinary calculi and could fail to detect some elements into the stone. Physical methods, in counterpart, are becoming more and more used in high-volume laboratories. The present manuscript will provide a review on analytic methods, and review all the information that should be included into an appropriate morpho-constitutional analysis.ConclusionThis report can supply an excellent summarization of the stone morphology and give the opportunity to find specific metabolic disorders and different lithogenic process into the same stone. Here, specific chemical types with their different crystalline phases are shown in connection with their different etiologies involved.

The Number of Cores Taken in Patients Diagnosed with a Single Microfocus at Initial Biopsy is a Major Predictor of Insignificant Prostate Cancer

PURPOSE Patients with a single microfocus of prostate cancer at initial biopsy represent the ideal candidates for active surveillance. We investigate whether the number of cores taken affects the concordance rate between microfocus of prostate cancer and the confirmation of a pathologically insignificant prostate cancer at radical prostatectomy. MATERIALS AND METHODS Data were analyzed from 233 patients with a single microfocus of prostate cancer at initial transrectal prostate biopsy (a single focus of Gleason 6 involving 5% or less of the core) subsequently treated with radical prostatectomy. The chi-square test, cubic spline analyses and logistic regression analyses were used to depict the relationship between the number of cores taken and the probability of confirming the presence of an indolent disease (pathologically confirmed insignificant prostate cancer defined as radical prostatectomy Gleason score 6 or less, tumor volume 0.5 ml or less and organ confined disease). RESULTS Overall 65 patients (27.9%) showed pathologically confirmed insignificant prostate cancer at radical prostatectomy. The rate of pathologically confirmed insignificant prostate cancer was 3.8%, 29.6% and 39.4% in patients who underwent biopsy of 12 or fewer cores, 13 to 18 cores and 19 or more cores, respectively (p <0.001). After adjusting for the available confounders, age (p = 0.04), number of cores taken (p <0.001) and prostate specific antigen density (p <0.02) were independent predictors of pathologically confirmed insignificant prostate cancer. CONCLUSIONS Of patients diagnosed with a single microfocus of prostate cancer the number of biopsy cores taken was a major independent predictor of having pathologically confirmed insignificant prostate cancer at radical prostatectomy. Therefore, when active surveillance is considered as a possible alternative in patients with microfocus of prostate cancer, the number of cores taken should be taken into account in decision making.

Naftopidil for the treatment of benign prostate hyperplasia: a systematic review

Abstract Objectives: The aim of the study was to systematically review the effects of the adrenoreceptor A1D antagonist naftopidil in the management of lower urinary tract symptoms (LUTS). Methods: A structured and comprehensive MEDLINE search was conducted for original articles, reviews, and metanalyses assessing the clinical pharmacology as well as the safety of naftopidil in the treatment of LUTS secondary to BPH. English-language publications dating from 1950 to 2013 were considered. Results: In the considered timeframe, 14 randomized clinical trials (RCT) were reported. Overall, the outcome measures assessed in the various reports included in the present review were changes from baseline in: International Prostate Symptom Score (IPSS), quality of life (QoL) score, maximum urinary flow rate (Qmax), residual volume (PVR), and adverse effects. Although additional well designed, worldwide, placebo-controlled and randomized studies are necessary to confirm the long-term outcomes of naftopidil pharmacotherapy, current data suggest that naftopidil administration in BPH patients provides comparable improvements in total IPSS, QoL, and urinary symptoms from baseline relative to 0.2 mg/d tamsulosin and 8 mg/d silodosin. However, improvements in Qmax are generally less with naftopidil than with tamsulosin. Reported adverse effects related to naftopidil administration are negligible and usually mild. Conclusion: It remains unknown whether the data reported on naftopidil in the Japanese population are applicable in symptomatic BPH patients from western countries given that: (1) no English-language clinical trials have compared naftopidil to placebo in Western countries; (2) all clinical trials available were carried out in Japan; (3) in the comparative studies with tamsulosin, the dose of this drug was lower than the recommended dose in Western countries; (4) no data from long-term clinical trials evaluating drug safety beyond 18 weeks.

Silodosin and tadalafil have synergistic inhibitory effects on nerve-mediated contractions of human and rat isolated prostates.

Lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH) are associated with erectile dysfunction. Alpha-1-adrenoceptor antagonists are effective drugs for treating symptomatic BPH. Clinical data show improvements in LUTS by phosphodiesterase 5 inhibitors. This study aimed to evaluate effects of silodosin, a highly selective α1A-adrenoceptor antagonist, alone or in combination with the phosphodiesterase 5 inhibitor tadalafil on contractions of isolated human and rat prostates. In organbath studies, effects of increasing concentrations of silodosin (1 nM-1 µM) and tadalafil (100 nM-100 µM) on contractions by electrical field stimulation or phenylephrine of human and rat prostate strip preparations were investigated. The combination silodosin and tadalafil reduced electrically-induced contractions of human prostate preparations better than single drugs alone. At any frequencies (1-32 Hz), inhibitory effects of combined therapy (P-values vs single drug) in human tissue were 26-42% (1 nM silodosin+100 nM tadalafil; P<0.05), 40-58% (10 nM silodosin+1 µM tadalafil; P<0.001-0.05), 56-67% (100 nM silodosin+10 µM tadalafil; P<0.01-0.05), and 33-55% (1 µM silodosin+100 µM tadalafil P<0.01-0.05). Similar findings were obtained in rat prostate preparations. In human and rat prostate tissue, the drug combination exerted similar inhibitory effect on phenylephrine contractions as silodosin alone. Silodosin plus tadalafil had greater potency than each drug alone to inhibit prostate contractions to electrical field stimulation but not to phenylephrine. This study supports the clinical application of a combination of an α1A-adrenoceptor antagonist and a phosphodiesterase 5 inhibitor for symptomatic BPH and suggests that the drug combination requires endogenous nerve-activity for optimal effect.

Confocal Laser Endomicroscopy in the Management of Endoscopically Treated Upper Urinary Tract Transitional Cell Carcinoma: Preliminary Data

PURPOSE To describe our initial experience with confocal laser endomicroscopy (CLE) for the evaluation and treatment of patients with upper urinary tract transitional cell carcinoma (UUT-TCC). MATERIALS AND METHODS Preliminary data were analyzed from 11 patients with suspicion of UUT-TCC scheduled for flexible ureteroscopy (f-URS) and consensual holmium-YAG laser tumor ablation. CLE was performed before endoscopic biopsy and laser photoablation of the suspected lesion using a 3F-diameter flexible probe UroFlex™ B (Cellvizio® system; Mauna Kea Technologies, Paris, France), which allows to obtain microscopic resolution imaging (3.5 μm), with a field of view of 325 μm and a depth of tissue imaging of 40 to 70 μm. Video sequences were analyzed offline and thereafter compared with histopathologic findings. RESULTS CLE technique was feasible and showed good quality imaging in all patients. Overall, the Cellvizio system provided reliable images of healthy urothelium when the probe was pointed toward normal tissue, showing umbrella cells on the surface and vessels in the lamina propria. Moreover, CLE displayed the characteristic features of high-density cellular aggregates and fibrovascular stalks in four patients with pathologically confirmed low-grade UUT-TCC. In the patient with pathologically confirmed high-grade UUT-TCC, more distorted microarchitecture and tortuous vessels were clearly recognized with CLE. CONCLUSIONS These preliminary data showed the feasibility of CLE technique when applied to the diagnosis of UUT-TCC. Further clinical studies are required to confirm CLE accuracy in distinguishing healthy urothelial tissue from malignant lesions, thus helping clinicians in targeting ureteroscopic biopsy and improving the conservative management of UUT-TCC patients.

The number of cores at first biopsy may suggest the need for a confirmatory biopsy in patients eligible for active surveillance-implication for clinical decision making in the real-life setting.

OBJECTIVE To assess whether the number of cores at first prostate biopsy affect pathologic findings at radical prostatectomy (RP) in potential candidates for active surveillance (AS). MATERIAL AND METHODS Two hundred seventy-five patients fulfilling Prostate Cancer Research International: Active Surveillance criteria (prostate-specific antigen level ≤ 10 ng/mL, prostate-specific antigen density <0.2 ng/mL/cm(3), number of positive cores ≤ 2, T1c-T2 clinical stage, Gleason score [GS] ≤ 6) underwent RP between 2005 and 2013 at a single institution. Patients were stratified into 3 groups according to different biopsy schemes (≤ 12 vs 13-18 vs ≥ 19 cores). Rates of pathologically confirmed insignificant prostate cancer (pIPCa; defined as RP GS ≤ 6, tumor volume ≤ 0.5 mL, and organ-confined disease) and unfavorable disease (UD, defined as non-organ-confined disease and/or pathologic GS ≥ 7) at RP were stratified according to the biopsy schemes. Logistic regression analyses tested the effect of preoperative variables in predicting pIPCa and UD at RP. RESULTS Of all, 23.3% and 33.4% patients harbored pIPCa and UD, respectively. pIPCa and UD were found in 15.7%, 32.1%, 25.3% (P = .04) and in 48.1%, 23.8%, 24.1% (P <.001) patients with ≤ 12, 13-18, ≥ 19 cores, respectively. At multivariate analyses, number of biopsy cores emerged as an independent predictor of both pIPCa (≤ 12 vs 13-18 cores: odds ratio [OR] = 2.34; P = .02) and UD (≤ 12 vs 13-18 cores: OR = 0.39; P <.01; ≤ 12 vs ≥ 19 cores: OR = 0.38; P <.01). CONCLUSION Among candidates for AS, number of biopsy cores emerged as an independent predictor of pIPCa and UD at RP. These findings would suggest that the extent of initial biopsy sampling should be considered when addressing patients to AS and before planning any surveillance strategies.

Immediate Nephroureterectomy or After Attempting Conservative Treatment, on Elective Indications, for Upper Urinary Tract Urothelial Carcinoma: Comparison of the Pathology Reports on a Retrospective Monocentric Study.

OBJECTIVE Conservative treatment (CT) with flexible ureteroscopy and laser ablation is an alternative to radical nephroureterectomy (RNU) for the treatment of the upper urinary tract urothelial carcinoma (UTUC). The purpose of this study was to compare the pathology results obtained after immediate RNU or after attempt of CT for elective indication. PATIENTS AND METHODS A retrospective study was conducted in a single tertiary center. All patients who had an RNU for urothelial carcinoma between 2007 and 2012 have been included. The patients were classified into two groups: group 1 is immediate RNU, and group 2 is RNU after CT (only elective indications). Preoperative data collected were as follows: age, sex, chronic kidney failure, radiological classification for cancer staging (TNM), tumor size, localization, and multifocal indication of CT. The pathological RNU data collected were tumor stage and grade. The T stage was divided into two groups (primary endpoint): pTa-T1-T2 and pT3-T4. The χ(2) test and Mann-Whitney was performed to compare the independent qualitative and quantitative variables, respectively. RESULTS A total of 51 patients were included (40 patients in the immediate RNU group and 11 patients in the delayed RNU group after CT). Patients in both groups had comparable characteristics regarding age, sex, location, T stage, and preoperative tumor grade. On final pathology, 23 tumors were classified as pTa-T1-T2 in the immediate RNU group compared with 6 in the delayed RNU group. Seventeen and five tumors were classified as T3 in group 1 and group 2, respectively. These results were not significantly different between both groups (p=0.866). The pathological RNU grade was not significantly different between the groups. CONCLUSION Within the limits of this retrospective study, the pathological RNU data showed no significant difference when RNU was done immediately or after CT for UTUC.

Do We Really Need to Wear Proper Eye Protection When Using Holmium:YAG Laser During Endourologic Procedures? Results from an Ex Vivo Animal Model on Pig Eyes.

PURPOSE We sought to evaluate the effect of holmium:yttrium-aluminum-garnet (Ho:YAG) laser exposure on ex vivo pig eyes and to test the protective action of different glasses in preventing eye lesions in case of accident. MATERIALS AND METHODS We pointed the tip of a Ho:YAG laser fiber from different distances (0, 3, 5, 8, 10, and 20 cm, respectively) toward the center of the pupil of the pig eye. The Ho:YAG laser was activated for 1 or 5 seconds at three different settings (0.5 J-20 Hz, 1 J-10 Hz, and 2 J-10 Hz, respectively). The experiment was repeated using laser safety glasses and eyeglasses. A total of 78 pig eyes were used. The effects of the Ho:YAG laser on pig eyes were assessed by histopathology. Comparable laser emission experiments were performed on thermal paper at different distances using different pulse energies. RESULTS Ho:YAG laser-induced corneal lesions were observed in unprotected eyes, ranging from superficial burning lesions to full-thickness necrotic areas, and were directly related to pulse energy and time of exposure and inversely related to the distance from the eye. When the laser was placed 5 cm or more, no corneal damage was observed regardless of the laser setting and the time of exposure. Similar distance/energy level relationships were observed on thermal paper. No damage was observed to the lens or the retina in any of the Ho-YAG laser-treated eyes or in any of the eyes protected by laser safety and eyeglasses. CONCLUSIONS Ho:YAG lasers can cause damage when set to high energy, but only to the cornea, from close distances (0-5 cm) and in the absence of eye protection. Eyeglasses are equally effective in preventing laser damage as laser safety glasses.