Giampaolo Siena

A Randomized, Placebo-Controlled Study to Assess Safety and Efficacy of Vardenafil 10 mg and Tamsulosin 0.4 mg vs. Tamsulosin 0.4 mg Alone in the Treatment of Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia

INTRODUCTION Safety and efficacy of tamsulosin and vardenafil are well established: however, there is no report regarding combined therapy with these drugs for lower urinary tract symptoms (LUTSs) secondary to benign prostatic hyperplasia (BPH). AIM To compare the safety and efficacy of tamsulosin 0.4 mg/day vs. tamsulosin 0.4 mg/day plus vardenafil 10 mg/day in patients with LUTS/BPH in a randomized trial with 12-week follow-up. METHODS We conducted a randomized, double-blind, placebo-controlled study on 60 men with persistent storage LUTS after 2-week run-in with tamsulosin. MAIN OUTCOME MEASURES International Prostate Symptom Score (IPSS), IPSS-bother, International Index of Erectile Function, Version 5 (IIEF-5) and Over Active Bladder questionnaire (OAB-q) scores, uroflowmetry data (Qmax, Qave), and postvoiding residual urine were recorded after run-in (baseline), and 2 and 12 weeks after treatment. Differences between vardenafil and placebo at different times were calculated with unpaired samples t-test. Between-group differences in change from baseline to 2 and 12 weeks were evaluated with analysis of variance. RESULTS We found a between-group significant difference from baseline to 12 weeks in the following: (i) Qmax (placebo: +0.07, vardenafil: +2.56, P = 0.034); (ii) Qave (placebo: -0.15, vardenafil: +1.02, P = 0.031); (iii) irritative-IPSS subscores (placebo: -1.67, vardenafil: -3.11, P = 0.039); and (iv) IIEF (placebo: +0.06, vardenafil: +2.61, P = 0.030). No patient reported any serious (grade ≥ 2) adverse event (AE). There were no differences in the incidence of common, treatment-related AEs between men undergoing combined therapy or tamsulosin alone. CONCLUSIONS The combination of tamsulosin and vardenafil for 12 weeks was well tolerated and more effective to improve both LUTS and erectile function, as compared with tamsulosin alone. Further studies are needed to assess the role of combined therapy of phosphodiesterase type 5 inhibitors and alpha blockers in treating LUTS/BPH.

Pathological characteristics and prognostic effect of peritumoral capsule penetration in renal cell carcinoma after tumor enucleation

OBJECTIVE To evaluate the pathological characteristics of peritumoral capsule (PC) and the prognostic effect of capsule penetration on tumor recurrence in patients treated with tumor enucleation for clinically intracapsular renal cell carcinomas (RCCs). METHODS AND MATERIALS PC status was analyzed in 304 consecutive patients with single intracapsular RCC. Degree and side of capsule penetration if present were evaluated. Mean (median, range) follow-up was 49 months (46, 25-69). Local recurrence rate, progression-free survival (PFS), and cancer-specific survival were the main outcomes. Statistical analyses included the Kaplan-Meier method, log-rank test, and univariate and multivariate Cox regression models. RESULTS Overall, 51% of RCCs had intact PC and free from neoplastic invasion (PC-), 34.9% had capsular penetration on the parenchymal side (PCK), and 14.1% had tumor invasion on the perirenal fat tissue side (PCF). None of the patients had positive surgical margins. The 5-year PFS rates for tumors PC-, PCK, and PCF were 97.5%, 96.7%, and 77.1%, respectively (P<0.0001). The multivariate Cox model showed PCF to be the sole significant independent predictor of PFS, whereas patients who had PCK did not present a significant increased risk in developing recurrence. CONCLUSIONS Tumor enucleation is an oncologically safe nephron-sparing surgery technique. PCF is a significant and independent predictor of tumor recurrence in patients with clinically intracapsular RCCs scheduled for nephron-sparing surgery. PCK does not predict the risk of recurrence.

Local recurrence after tumour enucleation for renal cell carcinoma with no ablation of the tumour bed: results of a prospective single‐centre study

Study Type – Therapy (individual cohort) 
Level of Evidence 2b

Simple enucleation for the treatment of highly complex renal tumors: Perioperative, functional and oncological results.

AIM To assess the role of simple enucleation (SE) for the treatment of highly complex renal tumors. METHODS Overall, 96 Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) classification score 10 to 13 renal tumors were treated with SE at our institution. All conventional perioperative variables, surgical, functional and oncological results were gathered in a prospectively maintained database. Survival curves were generated using a Kaplan-Meier method. Univariate analysis assessed the outcome differences. RESULTS Mean (± 1s.d.) clinical tumor diameter was 4.8 (± 1.6 cm). 70.8% of patients had ≥ cT1b stage. The PADUA score was recorded as 10, 11, 12 and 13 in 57.3%, 29.2%, 11.5%, and 2.1% of tumors respectively. Overall, 76 patients were treated with an open approach and 20 robotically. Mean warm ischemia time (WIT) was 19.2 min, and WIT greater than 25 min occurred in 14.6% of cases. Positive surgical margin (PSM) rate was 3.6% and trifecta was achieved in 64.3% of patients. Postoperative surgical complications occurred in 24% of patients, with 14.6% Clavien-Dindo grade 1-2, 8.3% grade 3, and 1% grade 4. Five-year cancer specific survival (CSS), recurrent free survival (RFS), and overall survival (OS) rates resulted 96.1%, 90.8% and 88.0%, respectively. Overall, 4.2% of patients experienced progressive disease. At follow-up, the mean decrease of eGFR from preoperative value was 13.9 ml/min. This was not significantly correlated with PADUA score (p = 0.69). The surgical approach was neither a predictor of Trifecta outcome, nor of postoperative complications, WIT > 25 min or PSM rate. CONCLUSIONS SE is an effective treatment for highly-complex renal tumors, with a potential key role to widen the NSS (nephron sparing surgery) indications according to guidelines.

Elective segmental ureterectomy for transitional cell carcinoma of the ureter: long-term follow-up in a series of 73 patients

Study Type – Therapy (outcome)

Morbidity of tumour enucleation for renal cell carcinoma (RCC): results of a single‐centre prospective study

Study Type – Therapy (case series) Level of Evidence 4

Robotic-assisted partial nephrectomy: the next gold standard for the treatment of intracapsular renal tumors.

Based on the GLOBOCAN 2008 estimates, published in 2011, over 110,000 new kidney cancer cases are expected in 2011, and will account for approximately 43,000 deaths among men from developed countries [1]. Due to increased utilization of diagnostic imaging for evaluation of patients with abdominal symptoms, small renal masses are being diagnosed with greater frequency, and over the last three decades a stage migration has been observed, with an overall decreasing size of stage I renal cell carcinoma (RCC) at diagnosis [2]. Data from the National Cancer Database over the 12-year period between 1993 and 2004 showed an increase in stage I disease and a decrease in stage II, III and IV disease (p ≤ 0.001). The size of stage I tumors also decreased from a mean of 4.1 cm in 1993 to 3.6 cm in 2003 [3]. In patients who have incidental detection of a renal tumor, there is, on average, a lower pathological stage and grade at diagnosis, which correlates with a significantly increased 5-year cancer-specific survival (CSS) as opposed to patients with symptomatic RCC [4]. Indeed, Jemal et al. report that the 5-year survival rate of patients diagnosed with kidney cancer has progressively increased from 51% in the mid1970s to 69% in the past decade [5], and Kane et al. showed a 3.3% increased CSS for patients diagnosed in 1998 compared with patients diagnosed in 1993 [3]. The increased diagnosis of small renal tumors has led to a concurrent rise in rates of surgical intervention and to an augmented interest in the various techniques of nephron-sparing surgery (NSS) [6]. In this scenario, renal preservation has been progressively prioritized, as approximately 26% of patients have impaired renal function prior to undergoing either NSS or radical nephrectomy (RN) and RN is a recognized independent risk factor in the development of chronic kidney disease postoperatively, cardiovascular events and overall mortality [7]. Weight et al. reviewed data of 1004 patients with clinical T1b renal masses undergoing NSS (n = 524) or RN (n = 480). Those patients undergoing RN lost significantly more renal function than those undergoing NSS. The average excess loss of renal function observed with RN was associated with a 25% (95% CI: 3–73) increased risk of cardiac death and 17% (95% CI: 12–27) increased risk of death from any cause on multivariate ana lysis [8]. Therefore, NSS is an attractive option and several studies have shown its oncological efficacy compared with RN. A dimensional cutoff is still a matter of discussion, but according to the European guidelines NSS should be performed whenever technically feasible in case of intracapsular RCCs up to 7 cm in diameter (T1a/b stage) [9]. Data Expert Rev. Anticancer Ther. 11(12), 1779–1782 (2011)

Robotic vs open simple enucleation for the treatment of T1a-T1b renal cell carcinoma: a single center matched-pair comparison.

OBJECTIVE To compare surgical, pathological, short-term functional data, and complications of endoscopic robotic-assisted simple enucleation (ERASE) and open simple enucleation (OSE). METHODS We undertook matched-pair analysis (age, tumor size, and preoperative aspects and dimensions used for an anatomical [PADUA] score) of 392 patients treated with simple enucleation (SE) for T1a-T1b renal tumors in our department, including 160 patients in the OSE group and 80 in the ERASE group. Perioperative outcomes were compared with univariate analysis. Variables associated with warm ischemia time (WIT) >25 minutes, complications, and postoperative acute kidney dysfunction (AKD) were assessed with multivariate analysis. RESULTS The groups were comparable in body mass index (BMI), comorbidity, and preoperative renal function. In the ERASE vs the OSE group, no significant differences resulted regarding WIT (18.5 vs 16.4 minutes, P = .5), complications, transfusion rate, reoperation rate for Clavien grade ≥ 3 complications, and positive surgical margin rate (2.9% vs 2.1%, P = .63). In elective patients, no significant difference resulted in variation of estimated glomerular filtration rate from baseline (8.5 vs 13.9 mL/min, P = .17) and AKD. In the ERASE group, the clamping of renal pedicle was used with a lower frequency (P <.0001), with lower estimated blood loss (EBL), longer operative time, and a 1-day shorter hospitalization (P = .001). On the multivariate analysis, the surgical approach was not independently associated with WIT >25 minutes, postoperative complications, and AKD. CONCLUSION The ERASE is a feasible technique with a positive surgical margin rate comparable to OSE; it showed WIT and complication rates similar to the open approach, along with the advantages of mini-invasivity.

Robot-assisted Kidney Transplantation: The European Experience

BACKGROUND Robot-assisted kidney transplantation (RAKT) has recently been introduced to reduce the morbidity of open kidney transplantation (KT). OBJECTIVE To evaluate perioperative and early postoperative RAKT outcomes. DESIGN, SETTING AND PARTICIPANTS This was a multicenter prospective observational study of 120 patients who underwent RAKT, predominantly with a living donor kidney, in eight European institutions between July 2015 and May 2017, with minimum follow-up of 1 mo. The robot-assisted surgical steps were transperitoneal dissection of the external iliac vessels, venous/arterial anastomosis, graft retroperitonealization, and ureterovesical anastomosis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Descriptive analysis of surgical data and their correlations with functional outcomes. RESULTS AND LIMITATIONS The median operative and vascular suture time was 250 and 38min, respectively. The median estimated blood loss was 150ml. No major intraoperative complications occurred, although two patients needed open conversion. The median postoperative estimated glomerular filtration rate was 21.2, 45.0, 52.6, and 58.0ml/min on postoperative day 1, 3, 7, and 30, respectively. Both early and late graft function were not related to overall operating time or rewarming time. Five cases of delayed graft function (4.2%) were reported. One case (0.8%) of wound infection, three cases (2.5%) of ileus, and four cases of bleeding (3.3%; three of which required blood transfusion), managed conservatively, were observed. One case (0.8%) of deep venous thrombosis, one case (0.8%) of lymphocele, and three cases (2.5%) of transplantectomy due to massive arterial thrombosis were recorded. In five cases (4.2%), surgical exploration was performed for intraperitoneal hematoma. Limitations of the study include selection bias, the lack of an open control group, and failure to report on patient cosmetic satisfaction. CONCLUSIONS When performed by surgeons with robotic and KT experience, RAKT is safe and reproducible in selected cases and yields excellent graft function. PATIENT SUMMARY We present the largest reported series on robot-assisted kidney transplantation. Use of a robotic technique can yield low complication rates, rapid recovery, and excellent graft function. Further investigations need to confirm our promising data.

Neurotensin Branched Peptide as a Tumor-Targeting Agent for Human Bladder Cancer

Despite recent advances in multimodal therapy, bladder cancer still ranks ninth in worldwide cancer incidence. New molecules which might improve early diagnosis and therapeutic efficiency for tumors of such high epidemiological impact therefore have very high priority. In the present study, the tetrabranched neurotensin peptide NT4 was conjugated with functional units for cancer-cell imaging or therapy and was tested on bladder cancer cell lines and specimens from bladder cancer surgical resections, in order to evaluate its potential for targeted personalized therapy of bladder cancer. Fluorophore-conjugated NT4 distinguished healthy and cancer tissues with good statistical significance (P < 0.05). NT4 conjugated to methotrexate or gemcitabine was cytotoxic for human bladder cancer cell lines at micromolar concentrations. Their selectivity for bladder cancer tissue and capacity to carry tracers or drugs make NT4 peptides candidate tumor targeting agents for tracing cancer cells and for personalized therapy of human bladder cancer.