The Evidence Paradox of the Effectiveness between the Paediatric and Adult Stone-Forming Population: A Narrative Review.

AIM/OBJECTIVE: To identify trends in the evidence base regarding the effectiveness of using α-blockers in children versus adults and compare outcomes. METHODS: A literature search up using the key words including urolithiasis/renal/ureteric stone in children/paediatric population, medical expulsive treatment (MET), α-blocker/alfuzosin/tamsulosin/doxazosin. Included were randomized or controlled clinical trials in paediatric stone formers (aged ≤18 years). Outcome measures for assessment included the overall stone expulsion rate, expulsion time, the number of pain episodes and adverse drug effects and/or reactions. Further comparison of efficacy levels using respective studies from the adult population was performed in order to identify trends, similarities and differences. RESULTS: A total of 8,259 articles were identified. Full text evaluation was possible for 28 articles. Although the picture is clearer in the paediatric group, the lack of reproducible results in adults certainly poses serious questions about data collection, analysis and interpretation in each individual study. The apparent paradox is due to the methodological differences between studies. CONCLUSION: The effectiveness of α-blockers and other medication as MET needs to be studied in multi-institutional, double-blind, placebo-controlled studies that would aim to prove superiority to placebo in contemporary clinical situations, with realistic end points and standardized outcome measure determination.

Current treatment of pelvic organ prolapse correlated with chronic pelvic pain, bladder and bowel dysfunction.

PURPOSE OF REVIEW: The purpose of this review is to critically analyze the relationship between symptoms of abnormal emptying of the bladder, urgency, pelvic pain, anorectal dysfunction and pelvic organ prolapse (POP) and to present evidence in order to show how many of the above mentioned symptoms can be cured or substantially improved by repair of specific pelvic ligaments. RECENT FINDINGS: In this review, we provide evidence to show how often these dysfunctions occur and how they can be cured in 42-94% by appropriate pelvic floor surgery in the longer term, up to 2 years. Laxity in ligaments and/or vaginal membrane due to damaged connective tissue may prevent the normal opening and closure mechanism of urethra and anus, because muscles need finite lengths to contract properly. Hypermobility of the apex can irritate the pelvic plexus causing chronic pelvic pain. In consequence, dysfunctions as abnormal emptying of the bladder, urgency, pelvic pain, fecal incontinence and obstructed defecation can occur in women with different degrees of POP. SUMMARY: In conclusion, it has to be recognized that women bothered by these symptoms should be examined for POP and appropriately advised for possibility of cure by pelvic floor surgery after careful selection. VIDEO ABSTRACT.

Renal Pseudoaneurysm after Flexible Ureterorenoscopy - An Unusual Complication.

Pseudoaneurysm following flexible ureterorenoscopy has not been reported so far. The etiology remains unclear as high intra-renal pressure, direct laser damage and damage through stiff guidewire puncture had all been avoided. We like to share this case to make urologists aware of this unusual complication and discuss possible causes and therapeutic approaches.

Current Trends in Urolithiasis Treatment in Various European Health Systems.

OBJECTIVE: In spite of readily available evidence-based guidelines on urolithiasis treatment, practical applications of treatments vary from country to country, or even within countries. The choice of treatment depends not only on the evidence, but often on general non-medical decision factors such as infrastructure, expertise, trends, patient demands, industry drive and reimbursement levels. In turn, many of these factors are interdependent and a result of the individual National Health System. METHOD: In an attempt to get a crude picture of trends and practices in stone treatment across Europe, a group of well-renowned international experts in the field were asked to reply to a set of standard questions relating to stone treatments, health systems and adherence to guidelines (level of evidence D = expert opinion). RESULTS: The above-mentioned interdependencies showed a varying picture in different countries. Overall, there is a trend away from lithotripsy and toward ureterorenoscopy. However, the choice of treatment is largely dependent on the affordability of infrastructure. Urologists may make choices based on the national reimbursement system, too. CONCLUSION: Without claiming to represent a scientifically sound study, this survey represents an interesting insight into a representative cross-section of European urological current practices and trends in urolithiasis treatment.

Acceptance of mixed scientific and clinical activities in a sub-speciality urology meeting.

Basic urolithiasis research into the causes for stone formation has been stagnating for a long time. Emergence of effective stone treatment modalities has shifted the public and clinicians' focus away from basic research towards symptomatic treatment solutions. This has occurred in spite of urolithiasis being a highly recurrent disease with an enormous socio-economic impact warranting a prophylactic and recurrence-preventing approach. An integrated, multidisciplinary translational platform has been developed in the form of urolithiasis meetings bringing together urologists, radiologists, nephrologists, basic scientists, dieticians and other stake holders interested in stone disease, for an exchange of knowledge, mutual education and understanding, and professional networking. Traditionally, such combined meetings are split into sessions addressing the specific interests of clinicians and scientists. At the recent Experts in Stone Disease Symposium we devised and implemented a program which mixed clinical and basic science activities throughout. We interviewed delegates between sessions regarding their acceptance of this novel concept using a standardized questionnaire. Sessions were well-attended, alleviating our initial anxiety that delegates would not appreciate a "no-choice" program. Of the 74 delegates who were interviewed, 60 (81%) were urologists, and 14 (19%) were non-urologists such as nephrologists, dieticians, and students. This is representative of the overall distribution of delegates at the conference. 71% felt that a closer co-operation and understanding between clinicians and scientists will ultimately benefit both groups, as well as patients; 95% found the mixed session approach beneficial, with half appreciating it as very good and innovative; 94% believed that they had derived useful learnings from the "other side"; 94% found that such mixed sessions are useful for their future work and understanding of the urolithiasis field as a whole; 94% agreed that mixed meetings of this type are useful in enhancing networking between the different stake holders in urolithiasis treatment and research. Finally, 85% would like to visit future mixed session meetings, and 89% would encourage their juniors to attend, too. Not only was a platform created to facilitate multidisciplinary exchange and networking, but delegates from several different backgrounds were encouraged to attend presentations in disciplines other than their own. The results of our survey confirm an overwhelmingly positive acceptance of this integrated multidisciplinary concept for stone meetings. As such, we are encouraged to continue with this concept in future conferences.

Accuracy of HistoScanning™ for the prediction of a negative surgical margin in patients undergoing radical prostatectomy.

OBJECTIVE: To assess the accuracy of HistoScanning™ (HS) as a visualization tool for preoperative treatment planning for nerve-sparing (NS) radical prostatectomy (RP). PATIENTS AND METHODS: A retrospective study was carried out on 80 patients with prostate cancer undergoing RP from October 2009 to December 2009. All patients underwent a HS procedure 1 day before surgery. Frozen sections (FSs) were performed on each latero-posterior side of the prostate to assess for the presence of cancer. On the HS analysis, the region corresponding to that removed at FS was assessed for suspicious lesions. The size of suspicious lesions within this volume was compared with the FS histopathological analysis. RESULTS: HS results corresponded to a 93% probability of having a negative surgical margin in the FSs. The presence of a HS volume ≥0.2 mL in a specific side was associated with a 3.7 times increased risk of a positive surgical margin at FS. CONCLUSIONS: HS has the potential to assist in the planning of NSRP. Larger, multicentre studies need to be performed for validation of these encouraging results.

High DGK-α and disabled MAPK pathways cause dysfunction of human tumor-infiltrating CD8+ T cells that is reversible by pharmacologic intervention.

CD8(+) tumor-infiltrating T cells (CD8-TILs) are found in many types of tumors including human renal cell carcinoma. However, tumor rejection rarely occurs, suggesting limited functional activity in the tumor microenvironment. In this study, we document that CD8-TILs are unresponsive to CD3 stimulation, showing neither lytic activity, nor lytic granule exocytosis, nor IFN-γ production. Mechanistically, no deficits in TCR proximal signaling molecules (lymphocyte-specific protein tyrosine kinase, phospholipase Cγ) were identified. In contrast, distal TCR signaling was suppressed, as T cells of TILs showed strongly reduced steady-state phosphorylation of the MAPK ERK and were unable to increase phosphorylation of ERK and JNK as well as AKT and AKT client proteins (IκB, GSK3) after stimulation. These deficits were tumor-specific as they were not observed in CD8(+) T cells infiltrating non-tumor kidney areas (CD8(+) non-tumor kidney-infiltrating lymphocytes; CD8-NILs). Diacylglycerol kinase-α (DGK-α) was more highly expressed in CD8-TILs compared with that in CD8-NILs, and its inhibition improved ERK phosphorylation and lytic granule exocytosis. Cultivation of TILs in low-dose IL-2 reduced DGK-α protein levels, increased steady-state phosphorylation of ERK, improved stimulation-induced phosphorylation of ERK and AKT, and allowed more CD8-TILs to degranulate and to produce IFN-γ. Additionally, the protein level of the AKT client molecule p27kip, an inhibitory cell cycle protein, was reduced, whereas cyclin E, which promotes G1-S phase transition, was increased. These results indicate that the tumor-inflicted deficits of TILs are reversible. DGK-α inhibition and provision of IL-2 signals could be strategies to recruit the natural CD8(+) T cells to the anti-tumor response and may help prevent inactivation of adoptively transferred T cells thereby improving therapeutic efficacy.