Correlation between penile cuff test and pressure-flow study in patients candidates for trans-urethral resection of prostate.

BACKGROUND: Aim of this study was to make a comparison between penile cuff test (PCT) and standard pressure-flow study (PFS) in the preoperative evaluation of patients candidates for trans-urethral resection of prostate (TURP) for benign prostatic obstruction (BPO). METHODS: We enrolled male patients with lower urinary tract symptoms candidates for TURP. Each of them underwent a PCT and a subsequent PFS. A statistical analysis was performed: sensitivity (SE), specificity (SP), positive predictive value (PPV), negative predictive value (NPV), likelihood ratio and ratio of corrected classified were calculated. Fisher exact test was used to evaluate relationships between PCT and maximal urine flow (Qmax): a p-value < 0.05 was considered statistically significant. RESULTS: We enrolled 48 consecutive patients. Overall, at PCT 31 patients were diagnosed as obstructed and 17 patients as unobstructed. At the subsequent PFS, 21 out of 31 patients diagnosed as obstructed at PCT were confirmed to be obstructed; one was diagnosed as unobstructed; the remaining 9 patients appeared as equivocal. Concerning the 17 patients unobstructed at PCT, all of them were confirmed not to be obstructed at PFS, with 10 equivocal and 7 unobstructed. The rate of correctly classified patients at PCT was 79% (95%-CI 65%-90%). About detecting obstructed patients, PCT showed a SE of 100% and a SP of 63%. The PPV was 68%, while the NPV was 100%. CONCLUSIONS: PCT can be an efficient tool in evaluating patients candidates for TURP. In particular, it showed good reliability in ruling out BPO because of its high NPV, with a high rate of correctly classified patients overall. Further studies on a huger number of patients are needed, including post-operative follow-up as well.

Percutaneous Tibial Nerve Stimulation (PTNS) efficacy in the treatment of lower urinary tract dysfunctions: a systematic review.

BACKGROUND: Percutaneous Tibial Nerve Stimulation (PTNS) has been proposed for the treatment of overactive bladder syndrome (OAB), non-obstructive urinary retention (NOUR), neurogenic bladder, paediatric voiding dysfunction and chronic pelvic pain/painful bladder syndrome (CPP/PBS). Despite a number of publications produced in the last ten years, the role of PTNS in urinary tract dysfunctions remains unclear. A systematic review of the papers on PTNS has been performed with the aim to better clarify potentialities and limits of this technique in the treatment of OAB syndrome and in other above mentioned urological conditions. METHODS: A literature search using MEDLINE and ISI web was performed. Search terms used were "tibial nerve" and each of the already mentioned conditions, with no time limits. An evaluation of level of evidence for each paper was performed. RESULTS: PTNS was found to be effective in 37-100% of patients with OAB, in 41-100% of patients with NOUR and in up to 100% of patients with CPP/PBS, children with OAB/dysfunctional voiding and patients with neurogenic pathologies. No major complications have been reported.Randomized controlled trials are available only for OAB (4 studies) and CPP/PBS (2 studies). Level 1 evidence of PTNS efficacy for OAB is available. Promising results, to be confirmed by randomized controlled studies, have been obtained in the remaining indications considered. CONCLUSIONS: PTNS is an effective and safe option to treat OAB patients. Further studies are needed to assess the role of PTNS in the remaining indications and to evaluate the long term durability of the treatment. Further research is needed to address several unanswered questions about PTNS.

Type-4 Phosphodiesterase (PDE4) Blockade Reduces NETosis in Cystic Fibrosis.

Neutrophilic inflammation is a key determinant of cystic fibrosis (CF) lung disease. Neutrophil-derived free DNA, released in the form of extracellular traps (NETs), significantly correlates with impaired lung function in patients with CF, underlying their pathogenetic role in CF lung disease. Thus, specific approaches to control NETosis of neutrophils migrated into the lungs may be clinically relevant in CF. We investigated the efficacy of phosphodiesterase (PDE) type-4 inhibitors, in vitro, on NET release by neutrophils from healthy volunteers and individuals with CF, and in vivo, on NET accumulation and lung inflammation in mice infected with Pseudomonas aeruginosa. PDE4 blockade curbed endotoxin-induced NET production and preserved cellular integrity and apoptosis in neutrophils, from healthy subjects and patients with CF, challenged with endotoxin, in vitro. The pharmacological effects of PDE4 inhibitors were significantly more evident on CF neutrophils. In a mouse model of Pseudomonas aeruginosa chronic infection, aerosol treatment with roflumilast, a selective PDE4 inhibitor, gave a significant reduction in free DNA in the BALF. This was accompanied by reduced citrullination of histone H3 in neutrophils migrated into the airways. Roflumilast-treated mice showed a significant improvement in weight recovery. Our study provides the first evidence that PDE4 blockade controls NETosis in vitro and in vivo, in CF-relevant models. Since selective PDE4 inhibitors have been recently approved for the treatment of COPD and psoriasis, our present results encourage clinical trials to test the efficacy of this class of drugs in CF.

Clear Cell carcinoma of the urinary bladder, A case report: Surgical and oncological management.

INTRODUCTION: Bladder cancer is a condition characterized by a broad spectrum of histological variants and clinical courses. The morphological description of histological variants is becoming increasingly important. The 75% of cases of these cancers are classified as pure urothelial carcinoma, while the remaining 25% is represented by other histological variants. The clear cell carcinoma is part of urothelial group and is a very rare entity. Oncological outcomes of this variant are still uncertain, but seems to be worst than for patiens with pure urothelial carcinoma. Moreover it seems to metastasize more easily to the lymph nodes. CASE REPORT: We present a case of a Caucasian 73 year old woman who, after an episode of gross hematuria, underwent an ultrasound of the urinary system, a cystoscopy and a total body computed tomography (CT) which confirmed the presence of a bladder neoformation. A transurethral resection of the bladder (TURB) was performed: the result of the histological examination was "poorly differentiated clear cell carcinoma". Given the rarity of histological characterization, we required a PET CT scan for more accurate staging, at which a suspected right pelvic lymph node was detected. We proposed a radical cystectomy with hysteroannessiectomy and extended lymphadenectomy. During the pre-hospitalization process, the patient developed anuria, with acute renal failure and bilateral hydronephrosis, which required the placement of bilateral nephrostomies; we performed the planned surgical procedure and the histological exam confirmed: high grade urothelial carcinoma with a high percentage (more than 70%) of clear cell carcinoma, with a strong local aggression and lymphnode metastates. We referred the patient to the oncologist who suggested a treatment plan within an immunotherapy based clinical trial and cisplatin. CONCLUSIONS: The morphological description of histological variants in bladder cancer is gaining increasing importance, especially for infiltrating and aggressive forms. The clear cell carcinoma is a very rare entity part of the urothelial group; they would seem more aggressive forms with an early lymph node involvement. This evidence is confirmed by the clinical case described, in which we have seen a large local aggression with an involvement of the lymph nodes of the right side of the pelvis of the pre-sacral ones. In these cases, the multimodal approach is crucial.

Safety and efficacy of retroperitoneal sutureless zero ischemia laparoscopic partial nephrectomy for low nephrometry score masses.

OBJECTIVES: To evaluate oncological feasibility and oncological and functional results of retroperitoneal sutureless zero ischemia laparoscopic partial nephrectomy (LPN). PATIENTS AND METHODS: Patients with posterior renal masses with low nephrometry score (RENAL ≤ 7) treated who underwent retroperitoneal sutureless zero ischemia.in a single center from January 2016 to November 2017. Clinical, surgical and pathological data were prospectively collected. Complications were reported according to the modified Clavien classification. RESULTS: Retroperitoneal sutureless zero ischemia laparoscopic partial nephrectomy was performed on 15 patients. The indication for nephron-sparing surgery was elective in 11 (73%) patients and imperative in 4 (27%). Median RENAL score was 5 (IQR: 5-7), median tumor diameter 25 mm (IQR: 20-35). In 11 cases, the tumor was located polar (85%), and in 2 cases hilar (15%). There were no intraoperative complications. No cases were converted to radical nephrectomy, and in no case parenchyma suture was necessary. Median operative time was 90 min (IQR:40-150), in no case clamping of the renal artery was necessary, median hospital stay was 4 days, median estimated blood loss (EBL) was 310 (180-500) ml. Pathological analysis showed renal cell carcinoma in 11 patients (85%), 9 (60%) staged T1a and 2 (13%) T1b. In 4 (27%) an oncocytoma was found. There were no positive surgical margins. One patient developed a major postoperative complication (postoperative renal bleeding requiring super-selective embolization). Trifecta rate was 93%. CONCLUSIONS: Sutureless retroperitoneal zero ischemia LPN for the treatment of low-complexity posterior renal masses showed to be safe and feasible. Longer follow-up and higher numbers of patients are, however, warranted to draw definitive conclusions on functional outcomes.

De novo synthesis of cyclooxygenase-1 counteracts the suppression of platelet thromboxane biosynthesis by aspirin.

Aspirin affords cardioprotection through the acetylation of serine529 in human cyclooxygenase-1 (COX-1) of anucleated platelets, inducing a permanent defect in thromboxane A2 (TXA2)-dependent platelet function. However, heterogeneity of COX-1 suppression by aspirin has been detected in cardiovascular disease and may contribute to failure to prevent clinical events. The recent recognized capacity of platelets to make proteins de novo paves the way to identify new mechanisms involved in the variable response to aspirin. We found that in washed human platelets, the complete suppression of TXA2 biosynthesis by aspirin, in vitro, recovered in response to thrombin and fibrinogen in a time-dependent fashion (at 0.5 and 24 hours, TXB2 averaged 0.1+/-0.03 and 3+/-0.8 ng/mL; in the presence of arachidonic acid [10 micromol/L], it was 2+/-0.7 and 25+/-7 ng/mL, respectively), and it was blocked by translational inhibitors, by rapamycin, and by inhibitors of phosphatidylinositol 3-kinase. The results that COX-1 mRNA was readily detected in resting platelets and that [35S]-methionine was incorporated into COX-1 protein after stimulation strongly support the occurrence of de novo COX-1 synthesis in platelets. This process may interfere with the complete and persistent suppression of TXA2 biosynthesis by aspirin necessary for cardioprotection.

Aspirin protects striatal dopaminergic neurons from neurotoxin-induced degeneration: an in vivo microdialysis study.

The effect of aspirin on dopaminergic neuronal damage induced by in vivo infusion of 1-methyl-4-phenylpiridinium iodide (MPP(+)) and 6-hydroxydopamine (6-OHDA) was studied in rats, using microdialysis. Rat striata were perfused with 1 mM MPP(+) or 6-OHDA for 10 min, causing peak levels of dopamine (DA) in the dialytic fluid, after 40 min. After 24 h, 1 mM MPP(+) was perfused again for 10 min and DA levels measured in the dialytic fluid, as an index of neuronal cell integrity. Pretreatment with Aspidol (lysine acetylsalicylate), 180 mg/kg i.p., 1 h before MPP(+) or 6-OHDA perfusion, did not modify DA extracellular output, on day 1, but restored MPP(+)-induced DA release on day 2, indicating a neuroprotective effect of Aspidol. Conversion of 0.5 mM 4-hydroxybenzoic acid (4-HBA) to 3,4-dihydroxybenzoic acid (3,4-DHBA) was measured as an index of reactive oxygen species (ROS). 6-OHDA, but not MPP(+), significantly enhanced 3,4-DHBA levels in the perfusion fluid. Aspidol (180 mg/kg, i.p.) reduced 6-OHDA-dependent increase of 3,4-DHBA levels. Meloxicam (50 mg/kg, i.p.), a specific cyclooxygenase-2 (COX-2) inhibitor, was ineffective against both neurotoxins. These data suggest that the protective effect of aspirin is due to different mechanisms of action according to the neurotoxin used, and it is independent from COX-2 inhibition.