Lucio Dell'Atti

Silodosin versus tamsulosin as medical expulsive therapy for distal ureteral stones: a prospective randomized study.

Introduction The aim of this study was to compare the safety and efficacy of silodosin (8 mg) versus tamsulosin (0.4 mg) as a medical expulsive therapy for distal ureteral stones. Methods 136 patients (aged 18 years or older) had presented with renal colic, were diagnosed to have a single, unilateral, radiopaque, proximal ureteral stone (range 4–10 mm in size), and agreed to undergo conservative management. For a 3-week period, 68 patients per group were assigned to the following treatments: Group A (gA) received tamsulosin 0.4 mg once daily, and Group B (gB) received silodosin 8 mg once daily. The time to expulsion, analgesic use, follow-up, endoscopic treatment and adverse effects of drugs were noted. Results Considering all the patients enrolled (136), one patient in gA and two patients in gB were unable to continue the study because of orthostatic hypotension within a week from commencing the treatment. A total of 133 patients (gA: 67; gB: 66) were included in this study. A stone expulsion rate of 61.2% (41 out of 67 patients) was observed in gA, and 80.3% (53 out of 66) was observed in gB. gB showed a statistically relevant advantage in terms of stone expulsion rate (p: 0.003), as well as in terms of expulsion time (weeks) (p: 0.002). No severe complications were recorded in both groups. Four patients (10.2%; 4/39) in gA and ten patients (22.7%; 10/44) in gB experienced retrograde ejaculation (<0.002). Conclusion The patients treated with silodosin showed a significant increase in expulsion rate and a decrease in expulsion time of lower ureteral stones in our study.

Age: “a natural anesthetic” in pain perception during the transrectal ultrasound-guided prostate biopsy procedure

Introduction The purpose of this study was to evaluate how the age factor might influence the tolerance biopsy examination, and then choose the modality of a local or general anesthetic technique. Materials and Methods This study evaluated 248 consecutive patients undergoing transrectal ultrasound-guided prostate biopsy for the first time. Each patient was treated under local anesthesia with lidocaine spray (10gr/100ml). Patients were divided into two groups according to age: Group A) 112 with age range ≤65 years, Group B) 136 with age range >65 years. Our first aim was to obtain a schedule of 14 biopsy samples in both groups. After the procedure each patient was given a verbal numeric pain scale (VNS), which was designed with 0 representing absence of pain and 10 the maximum pain they perceived in life. Results The average pain assessed with VNS was around 4.2 (2–8) and 2.8 (0–6) for the patients in Group A and Group B, respectively. The two groups appeared to be homogeneous in terms of pain perception regarding PSA value and gland volume, and appeared to have different pain scores with regard to age. In fact, the first group of patients, with the same anesthetic technique used, perceived more intense pain sensations related to acute biopsy. Conclusions In conclusion, we can say that a local anesthetic in clinical practice in the course of prostate biopsy is more sensitive if performed in a person aged 65 years.

Differential expression of microRNA501‐5p affects the aggressiveness of clear cell renal carcinoma

Renal cell carcinoma is a common neoplasia of the adult kidney that accounts for about 3% of adult malignancies. Clear cell renal carcinoma is the most frequent subtype of kidney cancer and 20–40% of patients develop metastases. The absence of appropriate biomarkers complicates diagnosis and prognosis of this disease. In this regard, small noncoding RNAs (microRNAs), which are mutated in several neoplastic diseases including kidney carcinoma, may be optimal candidates as biomarkers for diagnosis and prognosis of this kind of cancer. Here we show that patients with clear cell kidney carcinoma that express low levels of miR501‐5p exhibited a good prognosis compared with patients with unchanged or high levels of this microRNA. Consistently, in kidney carcinoma cells the downregulation of miR501‐5p induced an increased caspase‐3 activity, p53 expression as well as decreased mTOR activation, leading to stimulation of the apoptotic pathway. Conversely, miR501‐5p upregulation enhanced the activity of mTOR and promoted both cell proliferation and survival. These biological processes occurred through p53 inactivation by proteasome degradation in a mechanism involving MDM2‐mediated p53 ubiquitination. Our results support a role for miR501‐5p in balancing apoptosis and cell survival in clear cell renal carcinoma. In particular, the downregulation of microRNA501‐5p promotes a good prognosis, while its upregulation contributes to a poor prognosis, in particular, if associated with p53 and MDM2 overexpression and mTOR activation. Thus, the expression of miR501‐5p is a possible biomarker for the prognosis of clear cell renal carcinoma.

MicroRNA501-5p induces p53 proteasome degradation through the activation of the mTOR/MDM2 pathway in ADPKD cells

Cell proliferation and apoptosis are typical hallmarks of autosomal dominant polycystic kidney disease (ADPKD) and cause the development of kidney cysts that lead to end‐stage renal disease (ESRD). Many factors, impaired by polycystin complex loss of function, may promote these biological processes, including cAMP, mTOR, and EGFR signaling pathways. In addition, microRNAs (miRs) may also regulate the ADPKD related signaling network and their dysregulation contributes to disease progression. However, the role of miRs in ADPKD pathogenesis has not been fully understood, but also the function of p53 is quite obscure, especially its regulatory contribution on cell proliferation and apoptosis. Here, we describe for the first time that miR501‐5p, upregulated in ADPKD cells and tissues, induces the activation of mTOR kinase by PTEN and TSC1 gene repression. The increased activity of mTOR kinase enhances the expression of E3 ubiquitin ligase MDM2 that in turn promotes p53 ubiquitination, leading to its degradation by proteasome machinery in a network involving p70S6K. Moreover, the overexpression of miR501‐5p stimulates cell proliferation in kidney cells by the inhibition of p53 function in a mechanism driven by mTOR signaling. In fact, the downregulation of this miR as well as the pharmacological treatment with proteasome and mTOR inhibitors in ADPKD cells reduces cell growth by the activation of apoptosis. Consequently, the stimulation of cell death in ADPKD cells may occur through the inhibition of mTOR/MDM2 signaling and the restoring of p53 function. The data presented here confirm that the impaired mTOR signaling plays an important role in ADPKD.

Feasibility and safety of laparoscopic nephrectomy in uremic patients with end-stage renal disease.

Introduction The purpose of this study was to analyse the feasibility and safety of laparoscopic radical nephrectomy (LRN) vs. open radical nephrectomy (ORN), in terms of perioperative and postoperative outcomes, in uremic patients. Methods Between September 2007 and December 2013, 19 patients with end-stage renal disease (ESRD), who underwent LRN or ORN for chronic pyelonephritis, renal calculi, hydronephrosis, renal tumors, complicated cyst, or associated polycystic kidney, were retrospectively analysed. All patients with complete preoperative clinical and intraoperative parameters, including age at surgery, gender, body mass index (BMI), American Society of Anesthesiologists (ASA) score, surgical technique, operation time, complications, were available for further analyses. The 30-day complication rate in both groups was retrospectively review and graded according to the modified Clavien System in five grades. Results Overall, nine (47.3%) vs. 10 (52.7%) patients underwent LRN vs. ORN, respectively. The mean ASA score (2.7 ± 0.8 vs. 2.9 ± 0.7) did not show statistically significant differences in both groups (p = 0.632). None of the patients in G1 was converted to open surgery for intraoperative complications or CO2 retention. The estimated blood loss was 223 ± 155 mL in G1 and 455 ± 134 mL in G2 (p<0.005). Both groups were comparable with regard to mean operation time. The mean hospital stay was 5.95 ± 1.85 days in G1 and 8.10 ± 1.67 days in G2 (p<0.001). Conclusions The present study revealed that laparoscopic surgery in uremic patients might be performed safely under the expertise of an experienced laparoscopic team. This surgical technique is a minimally invasive treatment, reduces blood loss, shortens postoperative hospital stay, minimizes wound pain, and encourages an earlier return to normal activity.

The impact of core length on prostate cancer diagnosis during a standard 14-core prostate biopsy scheme.

Introduction Even if many studies in the literature purposed to evaluate the improvement of the prostate biopsy (PBx), few studies assessed the diagnostic value of core length in PBx. In this study, we evaluated the length of needle cores sampled during transrectal PBx (TRUSBx) and its impact on cancer diagnosis in a standard 14-core scheme. Methods Medical records of 573 patients who underwent an initial TRUSBx with 14-cores scheme for suspicious prostate cancer (PCa) at our Department were reviewed. The PBx procedure and pathological evaluation were standardized. Cores lengths were compared in patients with versus without cancer, and were divided into group A and B, respectively. Statistical analysis was done to define an acceptable cut-off for biopsy length. Results The mean age of the entire cohort was 62.1 ± 7.2 years, while median total prostate-specific antigen (PSA) and prostate volume were 4.2 ng/ml and 44.7 ml, respectively. PCa was showed in 33.3% of patients. Mean core length in group A versus B was 11.9 ± 3.9 versus 11.1 ± 3.2 mm (p = 0.016). Thus, core lengths were significantly longer in patients with cancer. There were no statistically significant differences when we considered the whole length of cores sampled from the right lobe (p = 0.58) and left lobe (p = 0.34). Conclusions The cancer detection rates in cores may be increased by core length in PCa patients during a TRUSBx. Our results suggest a core length of greater than 11.8 mm as a cut-off for quality warranty.

[Use of 5-phosphodiesterase inhibitors in patients with LUTS secondary to BPH: our experience and review of the literature].

INTRODUCTIONnThe phosphodiesterase inhibitors are used in the treatment of ED and there are increasing data of effects of these drugs on bladder and urethral relaxation as well as of prostatic smooth muscles that may relief the symptoms of BPH. This study was conducted to evaluate the role of Tadalafil (a PDE-5 inhibitor) in combination with standard therapy for the treatment of BPH.nnnMATERIALS AND METHODSnIn this randomized clinical trial of 165 patients with obstructive and irritative urinary tract symptoms due to BPH, IPSS ≥8, Iief ≥11, Q-max from 5 mL/s to 15 mL/s and residual urine volume (RUV) <120 mL, there was indication for surgical intervention. These patients were randomly allocated in three groups. Each patient received a therapeutic treatment daily for 12 weeks. Group A received treatment with tamsulosin 0.4 mg and tadalafil 5 mg, Group B received a standard treatment with tamsulosin 0.4 mg for BPH and Group C received only one treatment with tadalafil 5 mg.nnnRESULTSnThere was no significant difference in terms of IPSS score, Qmax and RUV before treatment in the three groups tested. Analysis of the data shows that in patients treated with tamsulosin and tadalafil IPSS, IIEF and QoL were significantly improved in a different way than in the other two groups, while the Qmax and RUV did not show a significant change in the three groups, remaining almost constant.nnnCONCLUSIONSnThe PDE-5 inhibitor improves quality of life and urinary symptoms in patients with LUTS suggestive of BPH, but doesnt have any significant effect on Qmax and RUV.