PI3K/AKT pathway genetic alterations and dysregulation of expression in bladder cancer.

PURPOSE: To examine the involvement of specific components of the PI3K/AKT pathway in urinary bladder cancer development. METHODS: Samples from 65 tumors and 13 normal bladder tissues were collected. Genomic DNA isolation from snap-frozen and paraffin-embedded laser-microdissected tissues was followed by Sanger sequencing, whereas total RNA was purified for use in RT-PCR analyses. Immunohistochemistry was carried out on sections of paraffin-embedded biopsy material. RESULTS: Three pathogenic mutations (two missense and one frameshift) were identified in exon 20 of PIK3CA {c.3140A>G (p.His1047Arg), c.[3172A>T(;)3174C>T] (p.lle1058Phe), c.3203dupA (p.Asn1068Lysfs*5)} after laser capture microdissection, whereas PTEN mRNA expression was found to be downregulated in bladder cancer tissues compared to normal bladder urothelium. Upregulation of cytoplasmic and nuclear p-AKT expression was detected in low grade tumors, whereas in infiltrating carcinomas p-AKT was shown to be downregulated and confined to the cytoplasm. PTEN expression was weak and mainly cytoplasmic in superficial tumors, but stronger and nuclear in the infiltrating tumors. CONCLUSIONS: PI3K/AKT pathway activation is crucial for bladder cancer initiation and progression. In this context, PIK3CA, p-AKT and nuclear PTEN could be used along with other biomarkers for prognosis and selection of appropriate therapy in the clinical management of bladder cancer.

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.

Calcification of the vas deferens and seminal vesicles: a review.

INTRODUCTION: Calcification of the vas deferens and seminal vesicles is a rare condition of unknown incidence. It has been described in association with diabetes, hyperparathyroidism and genitourinary tuberculosis, amongst other conditions. Little is known about the clinical significance and management of this condition. We review the literature in an effort to find answers about an entity that is frequently appreciated as an incidental finding. MATERIALS AND METHODS: An electronic database search was performed (Medline) using the key words: vas deferens; seminal vesicles; calcification, alone or in combination. Articles were selected according to relevance and quality of evidence. RESULTS: The search included published manuscripts between 1960 and 2012. A total of 17 relevant publications were identified. The majority were written in the English language and mostly consisted of case presentations and reports of radiologic findings. CONCLUSION: Calcification of the vas deferens and seminal vesicles is a rare condition. However, it may be implicated in male factor infertility and symptoms from the urogenital tract. Treatment should be directed towards the underlying cause on an individual basis. It is unknown whether control of the primary process has any effects on the histopathological appearance of the ducts and/or their improvement of function.

Laparoscopic varicocelectomy in the management of chronic scrotal pain.

BACKGROUND AND OBJECTIVES: To evaluate the usefulness of laparoscopic varicocelectomy in the management of chronic scrotal pain. METHODS: Between 2009 and 2011, 48 patients in total were treated with laparoscopic varicocelectomy for dull scrotal pain that worsened with physical activity and was attributed to varicoceles. All patients were followed up at 3 and 6 months and biannually thereafter with a physical examination, visual analog scale score, and ultrasonographic scan in selected cases. RESULTS: The mean age was 38.2 years (range, 23-54 years). The mean follow-up period was 19.6 months (range, 6-26 months). Bilateral varicoceles were present in 7 patients (14.6%), and a unilateral varicocele was present in 41 (85.4%). The varicocele was grade 3 in 27 patients (56.3%), grade 2 in 20 (41.6%), and grade 1 in 1 (2.1%). The mean preoperative visual analog scale score was 4.8 on a scale from 0 to 10. The mean postoperative visual analog scale score at 3 months was 0.8. After the procedure, 42 patients (87.5%) had a significant improvement in the visual analog scale score (P<.001); 5 (10.4%) had symptom improvement, although it was not statistically significant; and 1 (2.1%) remained unchanged. During follow-up, we observed 5 recurrences (10.4%) whereas de novo hydrocele formation was identified in 4 individuals (8.3%). CONCLUSION: Laparoscopic varicocelectomy is efficient in the treatment of symptomatic varicoceles with a low complication rate. However, careful patient selection is necessary because it appears that individuals presenting with sharp, radiating testicular pain and/or a low-grade varicocele are less likely to benefit from this procedure.

Hyoscine N-butylbromide (Buscopan®) in the treatment of acute ureteral colic: what is the evidence?

OBJECTIVE: To investigate the evidence for the use of hyoscine N-butylbromide (HBB) in the treatment of acute renal colic. METHODS: A literature search was performed using the keywords 'hyoscine N-butylbromide', 'ureteral colic', 'spasmolytic', 'anticholinergic' and 'analgesia'. The articles were given the appropriate level of evidence according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence guidelines. RESULTS: The analgesic effect of HBB as monotherapy is inferior to that of opioids and/or non-steroidal anti-inflammatory drugs (NSAIDs). It does provide an analgesic and antispasmodic effect, but not as long-lasting as NSAIDs. HBB does not serve as an adjunct to opioids. Furthermore, it does not facilitate passage of ureteral stones and has no effect on expulsion rate. CONCLUSIONS: HBB is often used where urinary tract smooth muscle spasm is thought to be part of the pathophysiological process. According to the evidence, administration of HBB follows non-peer-reviewed protocols which are based on empiric recommendations. Its role is still unclear, as it appears to have no advantage when used as monotherapy over established forms of analgesia. There appears to be a time-dependent relation to pain reduction following parenteral administration, but this needs to be confirmed by more prospective randomized cohorts.

How to conduct a successful workshop: The trainees' perspective.

OBJECTIVES: To define the success of a medical workshop from the trainees' perspective, where a medical workshop is a scientific event with the aim of presenting updated knowledge and to teach medical skills to the participants. In surgical specialties, it contributes to the development and maintenance of surgical skills. METHODS: Medline was searched for the previous 4 months to identify articles with combinations of the keywords 'workshops', 'training', 'simulators', and 'virtual reality'. Further articles were obtained by manually searching the reference lists of identified papers. We also obtained information and critical aspects of view from other trainees. RESULTS: Based on 30 articles from the Medline search, and mostly from the trainees' perspective, we present the basic characteristics of a successful workshop. The objective of the workshop, appropriate faculty members and presenters, highly motivated participants, the use of simulators and evaluation sheets, the venue and the registration fees all have a major role in the success of a workshop. CONCLUSIONS: A successful workshop is that from which trainees have grasped most of the knowledge and skills imparted to them, with a positive progression reflected on their learning curve. Workshops are a current necessity and all efforts should be made to achieve the desired result from the trainees' perspective.

The use of a thermoexpandable metal alloy stent in the minimally invasive management of retroperitoneal fibrosis: a single center experience from the United kingdom.

PURPOSE: To review our experience with and the effectiveness of the ureteral Memokath 051 metallic stent for the minimally invasive management of retroperitoneal fibrosis (RPF). PATIENTS AND METHODS: We retrospectively reviewed the records of patients with RPF who were treated between April 2008 and February 2013. Success was defined as improvement of renal function and lack of complications after stent placement. Follow-up was at 6 weeks, 3 months, 6 months, and annually thereafter. RESULTS: A total of 14 patients were identified. The study included eight female and six male patients. Mean age was 60.2 years±8.4 standard deviation (SD). The majority of patients had idiopathic RPF (n=12, 85.7%). Stent placement was performed in 23 renal units in 14 patients, 9 (64.3%) of whom had bilateral disease. Ten (71.4%) patients had previously received medical treatment, while three (21.4%) presented with recurrent disease postureterolysis. The mean length of follow-up was 22.5 months (range 3-56 mos). Mean stricture length was 7.6 cm±6.2 SD on the right and 7.7 cm±5.1 SD (P=0.925) on the left. Patients tolerated the stents well with minimal discomfort. Ureteral obstruction was managed successfully in 78.6% of patients (n=11/14). All patients had improvement of renal function. CONCLUSIONS: To our knowledge, this is the first study using metal stents in patients with RPF. Retrograde placement of the ureteral Memokath 051 metal stent can be considered as a promising alternative for initial or salvage postureterolysis minimally invasive management of ureteral obstruction in RPF.

Thromboprophylaxis and bleeding diathesis in minimally invasive stone surgery.

With populations ageing and active treatment of urinary stones increasingly in demand, more patients with stones are presenting with an underlying bleeding disorder or need for regular thromboprophylaxis, by means of antiplatelet and other medication. A practical guide to thromboprophylaxis in the treatment of urinary tract lithiasis has not yet been established. Patients can be stratified according to levels of risk of arterial and venous thromboembolism, which influence the requirements for antiplatelet and anticoagulant medications, respectively. Patients should also be stratified according to their risk of bleeding. Consideration of the combined risks of bleeding and thromboembolism should determine the perioperative thromboprophylactic strategy. The choice of shockwave lithotripsy, percutaneous nephrolithotomy or ureteroscopy with laser lithotripsy for treatment of lithiasis should be determined with regard to these risks. Although ureteroscopy is the preferred method in high-risk patients, shockwave lithotripsy and percutaneous nephrolithotomy can be chosen when indicated, if appropriate guidelines are strictly followed.

Current status of minimally invasive endoscopic management of ureteric strictures.

Endourological techniques are used more often nowadays in the treatment of ureteric strictures of various etiologies. Advances in technology have provided new tools to the armamentarium of the endoscopic urological surgeon. Numerous studies exist that investigate the efficiency and safety of each of the therapeutic modalities available. In this review, we attempt to demonstrate the available and contemporary evidence supporting each minimally invasive modality in the management of ureteric strictures.

A self-expanding thermolabile nitinol stent as a minimally invasive treatment alternative for ureteral strictures in renal transplant patients.

BACKGROUND AND PURPOSE: Ureteral obstruction in renal transplant allografts secondary to strictures can pose a challenging problem. Its incidence is reported between 0.5% and 4.7%. Usually, open surgical repair is performed. We present a series of patients in whom a metal Memokath™ 051 stent has been used as a minimally invasive treatment alternative. METHODS: We analyzed our data on the use of thermo-expandable metallic Memokath 051 stents for ureteral strictures in renal transplant patients. RESULTS: Between 2003 and 2010, eight male kidney recipients with a mean age of 49 years and obstructed ureters after kidney transplantation were treated with ureteral Memokath insertion. In six patients, the obstruction was at the level of the anastomosis, and in two, at the pelviureteral junction. After a mean follow-up of 4 years, half of the stents are in situ providing a good graft function. The average indwelling time is 4 years. Spontaneous resolution of the stricture without the need for further stent insertion was seen in three patients after a mean indwelling time of 7.3 months. There was one treatment failure in a patient with an obstructed, dilated, and convoluted ureter that was unable to withhold the stent in situ. No perioperative complications were recorded in this series. The overall success rate was 87%. CONCLUSION: Ureteral stent placement with the Memokath 051 is a safe minimally invasive treatment alternative for ureteral strictures in renal transplant recipients.

The current role of percutaneous chemolysis in the management of urolithiasis: review and results.

The treatment of urolithiasis has changed dramatically over the past several decades. Novel technologies have led to new management protocols. Percutaneous chemolysis as a primary or adjuvant treatment for urinary tract stones has widely been neglected. We present our own experience with it and discuss it in the light of an extensive literature review. From a MEDLINE search on percutaneous chemolysis we evaluated the most important studies, a total of 58 articles, 43 case series and 15 review articles. In our unit between 2001 and 2011, 29 patients (mean age 62 years) with infectious staghorn calculi were treated with adjuvant percutaneous chemolysis post-percutaneous nephrolithotripsy. There were 17 women, with 10 complete and 14 partial staghorn stones (mean size 32 mm). Patients were generally deemed at high risk to undergo another procedure in the future. Suby G solution was used following an established protocol. Sixteen patients (55.1 %) were stone free after chemolysis, eight stones showed partial dissolution, half of them with so-called "insignificant" residual fragments <4 mm. Patients with residual stones underwent SWL. Mean follow-up was 5.25 years (1-11). One stone-free patient (6 %) and three of eight patients (37.5 %) with residual fragments post local chemolysis, developed new stones during follow-up. The often neglected percutaneous chemolysis represents a significant and effective.

Improving the durability of digital flexible ureteroscopes.

OBJECTIVE: To present the damage to digital flexible ureteroscopes after 1 year of use in a tertiary stone center and our strategy to reduce the damage. MATERIALS AND METHODS: Data regarding all procedures performed with 3 new digital flexible ureteroscopes (Olympus URF-V) were collected. We examined the conditions under which the damage occurred and retrieved the manufacturer's repair reports. Two study groups were created. Group 1 included all the procedures performed before the introduction of a set of guidelines for safe use of the digital flexible ureteroscopes and a stepwise credentialing process for new surgeons. Group 2 included all the procedures performed thereafter. RESULTS: A total of 141 procedures were performed in 122 patients. Five events of damage occurred in the first study group and were related to working in maximum deflection. In the second group only 3 events occurred. The damage affected the angulation system, working channel, or body shaft. No damage occurred to the imaging system of any ureteroscope. The changes that were made after the first 5 months of use resulted in a significant prolongation of the number of uses before damage occurred for every ureteroscope (10.6 vs 21.6 uses before damage, P = .035). CONCLUSION: The optical system of the new digital ureteroscopes is very durable; however, the overall longevity depends on the correct handling of their use. By following the proposed guidelines for safe use and with monitored training of new users, these instruments can have a significantly longer lifespan.

Colon perforation during percutaneous renal surgery: a 10-year experience in a single endourology centre.

The use of percutaneous renal surgery has been recently revolutionised with novel endourological instruments and techniques. However, the incidence, prevention and management of severe complications such as colon perforation still lack consensus. By presenting our 10-year experience, we would like to highlight the diagnosis and management of the rare complication of colon perforation.

Drugs for pain management in shock wave lithotripsy.

Objective. With this review, we provide a comprehensive overview of the main aspects and currently used drugs for analgesia in shockwave lithotripsy. Evidence Acquisition. We reviewed current literature, concentrating on newer articles and high-quality reviews in international journals. Results. No standardized protocols for pain control in SWL exist, although it is crucial for treatment outcome. General and spinal anaesthesia show excellent pain control but are only recommended for selected cases. The newer opioids and nonsteroidal anti-inflammatory drugs are able to deliver good analgesia. Interest in inhalation anaesthesia with nitrous oxide, local anaesthesia with deep infiltration of the tissue, and dermal anaesthesia with EMLA or DMSO has recently rekindled, showing good results in terms of pain control and a favourable side effect profile. Tamsulosin and paracetamol are further well-known drugs being currently investigated. Conclusion. Apart from classically used drugs like opioids and NSARs, medicaments like nitrous oxide, paracetamol, DMSA, or refined administration techniques for infiltration anaesthesia show a good effectiveness in pain control for SWL.

Expression of ERß and its co-regulators p300 and NCoR in human transitional cell bladder cancer.

OBJECTIVE: Several data support a possible role of estrogens in bladder carcinogenesis, mediated mainly through estrogen receptor-ß (ERß). We study the expression of ERß and its co-regulators p300 and nuclear co-repressor (NCoR) in patients with bladder cancer. PATIENTS AND METHODS: One hundred and eleven consecutive patients (74 males and 37 females), aged 23-90 years (mean 70 ± 10) diagnosed with transitional cell bladder cancer were included in this study. The control group consisted of 29 patients that underwent transurethral prostatectomy and consented to simultaneous bladder biopsies. Immunohistochemical studies took place on formalin-fixed, paraffin-embedded sections from the TUR (transurethral resection) specimens. We studied the expression of ERß, p300 and NCoR.χ(2) test was used to evaluate the relationship between the histological grade and ERß expression, grade and co-regulators expression and grade and gender. Spearman rank correlation coefficient (r) was used in order to estimate the direction and strength of correlations between histological grade and ERß-p300-NCoR expressions. The Cochran-Armitage test for trend was applied in order to examine possible trends across the ordered levels of histological grade. RESULTS: ERß was more frequently expressed in the nucleus of normal bladder epithelium compared to malignant bladder epithelium with statistical significant association (r = -0.25, p = 0.003). The p300 was expressed only in the nucleus of bladder cancer cells and a positive correlation between molecular expression and cancer progression was demonstrated (r = 0.55, p < 0.001). NCoR immunostaining was demonstrated in the nuclei of bladder cells. Nuclear staining was significantly higher in normal tissue than in cancer cells (r = -0.33, p < 0.001), with negative correlation. Furthermore, its expression in grade I tumors was significantly higher than in grade II (r = -0.46, p < 0.001) and grade III tumors (r = -0.51, p < 0.001). Thus, like ERß, NCoR expression in bladder epithelium decreased during cancer progression and loss of cell differentiation. There was no correlation between the levels of expression of the three proteins in normal bladder epithelium, but there was an inverse correlation between the nuclear expression of ERß and p300 in carcinomas (r = -3.88, p = 0.042). Statistical significant association was established when correlating ERß expression with NCoR expression (r = 0.273, p = 0.005), while co-regulators' nuclear expression did not correlate with each other (p > 0.05). CONCLUSIONS: In bladder carcinogenesis, we demonstrated inhibition in the expression of ERß and its co-repressor NCoR as well as increased expression of the co-activator p300.

Endourological management of ureteric strictures after kidney transplantation: Stenting the stent.

The incidence of ureteric obstruction after kidney transplantation is 3-12.4%, and the most common cause is ureteric stenosis. The standard treatment remains open surgical revision, but this is associated with significant morbidity and potential complications. By contrast, endourological approaches such as balloon dilatation of the ureter, ureterotomy or long-term ureteric stenting are minimally invasive treatment alternatives. Here we discuss the available minimally invasive treatment options to treat transplant ureteric strictures, with an emphasis on long-term stenting. Using an example patient, we describe the use of a long-term new-generation ureteric metal stent to treat a transplant ureter where a mesh wire stent had been placed 5 years previously. The mesh wire stent was heavily encrusted throughout, overgrown by urothelium and impossible to remove. Because the patient had several previous surgeries, we first considered endourological solutions. After re-canalising the ureter and mesh wire stent by a minimally invasive procedure, we inserted a Memokath® (PNN Medical, Kvistgaard, Denmark) through the embedded mesh wire stent. This illustrates a novel method for resolving the currently rare but existing problem of ureteric mesh wire stents becoming dysfunctional over time, and for treating complex transplant ureteric strictures.

Use of a long-term metal stent in complex uretero-ileal anastomotic stricture.

Uretero-ileal anastomotic stricture is a potentially serious late complication after ileal conduit formation, with a reported incidence of 3-9%. The standard management technique is open surgical revision of the anastomosis with reimplantation of the affected ureter. This is technically challenging and has potential significant morbidity for the patient. Advances in endourological techniques now offer a variety of less-invasive treatment options, like balloon dilatation or laser ureterotomy followed by stent insertion. What happens when such open and minimally invasive techniques fail? Recently, using a combined antegrade and retrograde approach, we inserted a novel, semi-permanent, dual-expansion thermo-expandable metallic alloy stent across a recurrent ileal-ureteric stricture. We describe the technique and potential advantages of this minimally invasive method. This minimally invasive treatment option is of interest, as in contrast to other stents, it does not require routine change, and is resistant to corrosion and urothelial ingrowth, hence ensuring ease of exchange or removal if required.