Introduction: After demonstrating their efficacy in metastatic urothelial cancer (UC), immune checkpoint inhibitors (ICI) are currently being tested in the neoadjuvant setting before radical cystectomy. In this systematic review, we analyze current available data and ongoing trials exploring the efficacy and safety of ICI neoadjuvant therapy in UC.
Evidence acquisition: A systematic search was performed including the combination of the following words: (["neoadjuvant" AND "immunotherapy"] AND ["bladder" AND "cancer"]). Three search engines (PubMed, Embase®, and Web of Science) were queried up to January 1, 2020. Study selection followed the PRISMA guidelines. After screening, 9 articles and abstracts fully compatible with the PICOS were included in the systematic review.
Evidence synthesis: The PURE-01 trial showed a 37% complete response (pT0) after neoadjuvant pembrolizumab. In the ABACUS trial, atezolizumab determined a complete response in 31% of patients. In both trials, an increased expression of PD-1 or PD-L1 was associated to an improved response to ICI. Moreover, ICI are well tolerated with grade III-IV adverse events in 6% of cases. In the PURE-01 trial, radical cystectomy after neoadjuvant ICI presents a similar complication rate compared to neoadjuvant chemotherapy, with fever (N.= 35, 52%) and ileus (N. = 21, 31%) being the most common postoperative complications. Numerous trials are currently recruiting to test ICI in the neoadjuvant setting, either alone, in combination immunotherapy or with chemotherapy.
Conclusions: Pembrolizumab and atezolizumab single agent demonstrated favorable results for ICI in the neoadjuvant setting. Patients with a higher tumor expression of PD-L1 appear to experience a higher response to ICI, although the adequate biomarker remains to be identified. Radical cystectomy appears to be safe after ICI treatment. The results of the currently ongoing prospective trial are awaited with impatience by the uro-oncologic community.
Introduction: Chronic obstruction and stones formation are common in pelvic ectopic kidney (PEK), and stone treatment in such conditions can be challenging. Aim of this systematic review was to examine all the available active treatment modalities for PEK stones in order to critically appraise their advantages and limitations.
Evidence acquisition: A search on Medline, Embase, and the Cochrane Library databases was performed to identify literature focused on the active treatment of PEK stones. Original articles, case report and case series were included in the search. The systematic review was conducted in accordance to the PRISMA checklist. The study period went from inception of databases to October 2019.
Evidence synthesis: Of the 256 articles identified, 23 met the inclusion criteria. 334 patients were included in the studies and 119 had stones in PEK. Five patients were treated with SWL, 40 with ureterorenoscopy, 37 with percutaneous nephrolithotomy both by ultrasound/X-Ray or lap-assisted puncture, and 37 with minimally invasive laparoscopic or robot assisted pyelolithotomy. Overall, stone free rate after first treatment was higher in minimally invasive laparoscopic or robot assisted pyelolithotomy (97.2%) compared to percutaneous nephrolithotomy (84.96%) and ureterorenoscopy studies (65.94%). The higher complication rate was reported in percutaneous nephrolithotomy not lap-assisted (33.3%).
Conclusions: The choice of the approach depends on different factors such as stone size, density and location in accordance with upper urinary tract alterations, kidney anatomy and operator experience. The choice of a retrograde, percutaneous or lap/robot approach should be carefully selected evaluating upper urinary tract anatomy and stone features.
Background: Renal cell carcinoma still represents 2-3% of all tumors but its mortality is decreased in the last decades due to the early detection of small masses and to the innovative surgical techniques. The aim of our study was to evaluate safety and feasibility of clampless and sutureless laparoscopic partial nephrectomy (CSLPN) in terms of intra- and postoperative functional results, complication rate and oncological outcome.
Methods: We evaluated patients undergoing CSLPN between July 2013 and December 2019. Inclusion criteria were single, organ confined tumor with size ≤4 cm, intraparenchymal depth ≤1.5 cm, renal nephrometry score between 4 and 6 and no close contact with the collecting system.
Results: Overall, 62 patients underwent CSLPN. Mean operative time was 105 minutes, mean intraoperative blood loss was 165 mL. Mean drain time and hospital stay were respectively 2.5 and 4.2 days. Mean 24 hours hemoglobin (Hb) decrease was 2.5 g/dL. No significative variations are described in pre- and postoperative renal function. Twelve patients had postoperative complications. At a median follow-up of 38.5 months all the patients are alive and disease free.
Conclusions: Different techniques have been proposed to reduce warm ischemia time (WIT). In our experience we found many benefits in an off-clamp procedure: it gives an ischemia-related advantage, reduces the overall operating time, eliminates the risks associated with the isolation of hilar vessels. In conclusion CSLPN is a safe and effective procedure for selected renal masses; it does not increase complication rate and offers excellent functional and oncological outcomes.
Introduction: The pathophysiology and management of male patients with lower urinary tract symptoms (LUTS) is still a matter of debate. In the past few years, the urothelium and the urinary microbiota represented important areas of research to improve the understanding and management of these patients. Aim of the present review was to summarize the available data on the urothelium and the microbiota related to male LUTS.
Evidence acquisition: A National Center for Biotechnology Information (NCBI) PubMed search for relevant articles published between January 2000 and December 2019 was performed using the medical subjects heading "urothelium," "microbioma," "microbiota," "urobioma," "urobiota," "benign prostatic hyperplasia," "benign prostatic enlargement," "lower urinary tract symptoms," "lower urinary tract dysfunction," "men," "male," "overactive bladder," "receptors." Exclusion criteria included: animal studies and studies on muscarinic and adrenergic pathways.
Evidence synthesis: The urothelium has been recently evaluated in humans to evaluate new possible markers and pathways. New possible targets for the treatment of male LUTS include the neural growth factor, the cannabinoid, the vanilloid and the ATP pathways. However, studies in humans are still needed to elucidate the exact role of these pathways in the management of male patients with LUTS. The available evidence on the urinary microbioma in male is poor. Standing to the available, urinary microbioma is evident in healthy urine in males. Moreover, the urinary microbioma varies depending on the method of collection, sexually transmitted disease status, inflammation and urinary symptoms. A possible role of probiotics in the management of LUTS in women has been proposed and may have a role in male patients as well.
Conclusions: The urothelium and the urinary microbiota are still poorly studied in men with LUTS. Most of the evidence and the hypothesis on the relationship between urothelium/urinary microbiota and LUTS comes from animal/in-vitro evidence while clinical trials are lacking. These pathways seem interesting even in LUTS pathogenesis in men but their possible role as a new therapeutic target is still an open debate.