Solifenacin in the Elderly: Results of an Observational Study Measuring Efficacy, Tolerability and Cognitive Effects.

INTRODUCTION: The study aimed to evaluate the efficacy and safety of solifenacin in older patients with overactive bladder (OAB). MATERIALS AND METHODS: Observational data on patients aged ≥70 years and the prescribed flexible dose of solifenacin for OAB were collected at 294 offices of German general practitioners. Baseline and week 12 data included type and severity of OAB symptoms, adverse events, quality of life, and change in cognitive function per Mini Mental State Examination (MMSE). RESULTS: Mean age of 774 patients was 78 ± 6 years. A decrease was observed in all OAB symptoms including a reduction of urinary urgency and micturition, each by 4 episodes per 24 h. No change in mean MMSE scores was apparent at week 12. Adverse events and treatment discontinuations were low at 5.8 and 0.5%, respectively. CONCLUSION: Solifenacin was well-tolerated while OAB symptoms declined at week 12. No relevant effect of solifenacin on cognitive function was observed in this elderly population.

Treatment of cT1a Renal Tumours in Germany: A Nationwide Survey.

OBJECTIVE: To identify clinical parameters influencing German urologists treating cT1a renal tumours, we performed a nationwide survey among members of the German urological associations (DGU and BDU). MATERIAL AND METHODS: In spring 2012, DGU and BDU members were invited to complete our survey. For 8 cases and 3 index patients, participants were asked about their preferred treatment. Multivariate analyses were used to identify significant parameters leading the responders to favour radical nephrectomy (RN) over nephron sparing surgery (NSS) as well as active surveillance (AS) over invasive treatment. RESULTS: Three hundred six (7.4%) forms were included in our analysis. In patients with larger tumours (4 vs. 2 cm, OR 3.16), endophytic growth (endophytic vs. exophytic, OR 2.70), hilar tumour location (perihilar vs. polar, OR 14.37), normal renal function (normal vs. decreased, OR 1.92) and elderly patients (elderly vs. young, OR 2.14) RN was preferred. Based on decreased renal function (decreased vs. normal, OR 12.74), elderly (elderly vs. young, OR 14.31) and hilar tumour location (perihilar vs. polar, OR 2.14), 77.2% of respondents recommended AS for selected patients. Treating physician factors had no influence on the treatment preference. CONCLUSIONS: Elderly patients with small tumours and impaired renal function were candidates for AS. Younger patients mainly underwent NSS. However, when the tumours' location was endophytic or hilar, RN was recommended.

Incidence of Cardiovascular Events after Nephrectomy - A Single Centre, Matched Pair Analysis between Donor and Tumour Nephrectomy in a Long Term Follow-Up.

INTRODUCTION: The study aimed to compare the incidence of cardiovascular events (CVEs) after donor nephrectomy (DN) and radical tumor nephrectomy (RN), according to an estimated glomerular filtration rate (eGFR), were evaluated over time. MATERIALS AND METHODS: Follow-up was collected for DN who underwent surgery from 1998 to 2007 for CVE and renal function. All DN were matched for age to patients treated by RN or adenoma enucleation (control group), who were eligible for DN. eGFR was estimated using the Cockgroft-Gould formula. Patients with preoperative comorbidities were excluded. RESULTS: Thirty DN (median age 48.9 years) were included with a median follow-up of 138.5 months (interquartile range 119-159). No significant differences in patients' characteristics were found preoperatively (p > 0.5). Four out of 30 DN developed a CVE (3 myocardial infarctions (MI), 1 stroke), 2 of 30 patients in the control group (both MI) and 8 of 30 RN patients (6 MI, 2 strokes, p > 0.05). Arterial hypertension developed in 14 DN (46.7%), in 12 (40%) after RN and in 15 controls. The CVE occurred after a median time of 68 months (5-231) and were related to a drop of ∼30% in the eGFR irrespective of the group. CONCLUSION: Decline of renal function after nephrectomy is the main risk factor for CVE. Close monitoring of renal function and new onset hypertension is warranted.

Bone scintigraphy predicts bisphosphonate-induced osteonecrosis of the jaw (BRONJ) in patients with metastatic castration-resistant prostate cancer (mCRPC).

OBJECTIVES: The aim of this study was to evaluate the role of bone scintigraphy (BS) in early prediction of clinically asymptomatic bisphosphonate (BP)-related osteonecrosis of the jaws (BRONJ) in patients with metastatic castration-resistant prostate cancer (mCRPC). MATERIAL AND METHODS: BS of mCRPC patients treated with BP was evaluated for pathologic tracer uptake of the jaws in BS suspicious for BRONJ. Results were compared to development of clinically evident BRONJ. Sensitivity, specificity and predictive values of BS for the detection of BRONJ as well as time from beginning of BP therapy to pathologic tracer uptake in BS and time from pathologic tracer uptake in BS to clinically evident BRONJ were determined. RESULTS: Thirty BP-treated patients were included. Nine patients (30%) had pathologic BS lesions of the jaws. Six patients (20%) developed BRONJ. Sensitivity and specificity of BS for BRONJ prediction were 67 and 79%. Median time from the start of BP treatment to pathologic tracer uptake in BS was 28 months (range 10-33) and from pathologic tracer uptake in BS to clinically evident BRONJ 6.5 months (range 2-19). Pathologic tracer uptake in BS was significantly more often observed in patients who developed BRONJ compared to patients who did not (p = 0.049; OR 7.6). CONCLUSIONS: Patients with pathologic tracer uptake in the jaws in BS significantly more often develop BRONJ. An unsuspicious BS is predictive for absence of BRONJ in the future. CLINICAL RELEVANCE: We conclude that when BS has been performed, it should not only be used to assess tumour stage and treatment response but also to check for pathologic tracer uptake in the jaws in BS to detect BRONJ at an early stage in mCRPC patients receiving bisphosphonates.

Bone Metastasis in Renal Cell Carcinoma is Preprogrammed in the Primary Tumor and Caused by AKT and Integrin α5 Signaling.

PURPOSE: Bone metastasis develops in 30% of all patients with renal cell carcinoma. We elucidated the mechanisms that lead to and predict bone metastasis of renal cell carcinoma. MATERIALS AND METHODS: Nine renal cell carcinoma primary cell lines and 30 renal cell carcinoma tissue specimens (normal and tumor tissue) were collected from 3 patients with no metastasis and 10 with lung or bone metastasis within 5 years after nephrectomy. Cell migration was analyzed in a Boyden chamber and proliferation was assessed by bromodeoxyuridine incorporation. Adhesion to fibronectin, and collagen I and IV was determined after cell staining. The expression and/or activity of cellular signaling molecules was quantified by Western blot. RESULTS: Compared to renal cell carcinoma cells from patients without metastasis, the migration of cells from patients with bone metastasis was enhanced 13.5-fold (p = 0.034), and adhesion to fibronectin and collagen I was enhanced 5.8-fold and 6.1-fold (p = 0.002 and 0.014, respectively). In general proliferation was decreased in metastasizing cells. In accordance with these results we detected higher activity of AKT (p = 0.011) and FAK (p = 0.054), higher integrin α5 expression (p = 0.052) and lower PTEN expression in primary cells from patients with bone metastasis compared to nonmetastasizing cells. An almost similarly altered expression pattern was also observed in the renal cell carcinoma tissue specimens and the normal renal tissue of patients with bone metastasis. CONCLUSIONS: We describe evidence that molecular predispositions determine the potential for bone metastasis to develop in renal cell carcinoma, which may serve as prognostic markers after initial tumor detection.

Pancreatic Fistulae after Urologic Surgery - A Single Centre Experience.

INTRODUCTION: To evaluate incidence, symptoms and management of postoperative pancreatic fistula (POPF) after urologic surgery based on our experience. MATERIAL AND METHODS: Database was searched for clinically evident POPF after urologic surgery between 1998 and 2014. Fistulae were graded using the POPF classification. Clinical course of every POPF patient was evaluated. RESULTS: During this time, 3,200 surgeries for renal, adrenal and retroperitoneal pathologies were performed. Twelve POPF occurred postoperatively in this series. Eight fistulae were POPF grade A, 3 POPF grade B and one POPF grade C. POPF became clinically evident after a median of 3 days (IQR 2-3). In all POPF grade A/B patients, secretion from the pancreatic fistula completely subsided under conservative therapy. In one POPF grade C patient with positive surgical margins of urothelial cancer, conservative treatment failed and the patient died due to POPF-related sepsis. CONCLUSIONS: POPF is a rare complication after urologic surgery. Conservative therapy is the first choice of treatment and will be successful in the majority of cases. Pancreatic fistula after surgery of recurrent malignancy may have a poor outcome.

High calcium concentration in bones promotes bone metastasis in renal cell carcinomas expressing calcium-sensing receptor.

BACKGROUND: The prognosis for renal cell carcinoma (RCC) is related to a high rate of metastasis, including 30% of bone metastasis. Characteristic for bone tissue is a high concentration of calcium ions. In this study, we show a promoting effect of an enhanced extracellular calcium concentration on mechanisms of bone metastasis via the calcium-sensing receptor (CaSR) and its downstream signaling molecules. METHODS: Our analyses were performed using 33 (11/category) matched specimens of normal and tumor tissue and 9 (3/category) primary cells derived from RCC patients of the 3 categories: non-metastasized, metastasized into the lung and metastasized into bones during a five-year period after nephrectomy. Expression of CaSR was determined by RT-PCR, Western blot analyses and flow cytometry, respectively. Cells were treated by calcium and the CaSR inhibitor NPS 2143. Cell migration was measured in a Boyden chamber with calcium (10 µM) as chemotaxin and proliferation by BrdU incorporation. The activity of intracellular signaling mediators was quantified by a phospho-kinase array and Western blot. RESULTS: The expression of CaSR was highest in specimens and cells of patients with bone metastases. Calcium treatment induced an increased migration (19-fold) and proliferation (2.3-fold) exclusively in RCC cells from patients with bone metastases. The CaSR inhibitor NPS 2143 elucidated the role of CaSR on the calcium-dependent effects. After treatment with calcium, the activity of AKT, PLCγ-1, p38α and JNK was clearly enhanced and PTEN expression was almost completely abolished in bone metastasizing RCC cells. CONCLUSIONS: Our results indicate a promoting effect of extracellular calcium on cell migration and proliferation of bone metastasizing RCC cells via highly expressed CaSR and its downstream signaling pathways. Consequently, CaSR may be regarded as a new prognostic marker predicting RCC bone metastasis.

Efficacy and tolerability of solifenacin in men with overactive bladder: results of an observational study.

PURPOSE: To evaluate the efficacy and safety of solifenacin for the treatment of OAB in men. METHODS: This prospective observational study, reflective of actual practice patterns, was conducted in men older than 18 years who were prescribed solifenacin for the treatment of OAB symptoms. Men with suspected bladder outlet obstruction were excluded. The primary efficacy measure was change in OAB symptoms after 12 weeks of solifenacin. Also assessed were changes in severity of urinary urgency, IPSS, quality of life, cognitive function, and adverse events. Data were analyzed using descriptive methods. RESULTS: A total of 799 men recruited at 251 centers, average age 67 years (range 27-92), received solifenacin 5 mg or 10 mg/day. Mean episodes of urinary urgency, frequency, and nocturia decreased by 4.4, 3.6, and 1.4 episodes/24 h, respectively. As per IPSS, severe urinary symptoms were reported by 20.4 % at baseline versus by 2.3 % at week 12. Both voiding and storage symptoms showed improvement. Patient-reported general health condition was excellent/good for 39 % at baseline increasing to 76 % at week 12. Adverse event rate was 5.5 %, and discontinuation of solifenacin due to an event was 1.6 %. No change in post-void residual urine volume was experienced in 80%, while an increase of ≥50 mL was observed in 2.2 %; no cases of acute urinary retention occurred. Baseline mean MMSE was 27.5 points versus 27.9 points at week 12. CONCLUSIONS: Solifenacin reduced all OAB symptoms, was well tolerated, and had no apparent effect on post-void residual urine volume. Cognitive function was unaltered in this population of older men with OAB.

[Botulinum toxin A for idiopathic overactive bladder in women]. / Botulinumtoxin A bei idiopathischer Blasenüberaktivität (iOAB) der Frau.

Following a description of the historic evolution of botulinum toxin A detrusor injections for neurogenic and nonneurogenic bladder overactivity, which was mainly driven by German-speaking countries, the terminological revolution of 2002 and the influence on design and outcomes of upcoming approval studies for the indication overactive bladder (OAB) are examined. OnabotulinumtoxinA (100 IU) for second-line treatment of OAB received European approval in 2013. Phase IV observational studies concerning therapeutic persistence and adherence with onabotulinumtoxinA are analyzed and compared with therapeutic alternatives. Predictors of treatment success and complications are identified and compared to the required preinterventional diagnostic effort. Since onabotulinumtoxinA and sacral neuromodulation (SNM) are competing for second-line OAB treatment, both options are compared with regard to differential indications, effectivity, durability and patient adherence. Gender-specific causes of urgency and urge incontinence in women are differentiated from the diagnosis of OAB and require priority treatment. On the basis of diagnostic examination results, an algorithm for invasive second-line treatment of OAB is presented, since overly liberal utilization of onabotulinumtoxinA in therapy-naive OAB patients has not proven superiority over oral antimuscarinergic standard therapy, which can only be explained by improper patient selection.

Treatment efficacy and outcomes using a third generation shockwave lithotripter.

OBJECTIVES: To evaluate the clinical efficiency of a third generation electromagnetic shock wave lithotripter, the Lithoskop(®) (Siemens, Erlangen, Germany), regarding outcomes, stone disintegration, retreatment and complication rates. To compare the results of the Lithoskop with other currently available systems and the reference standard lithotripter, the HM-3 (Dornier MedTech Europe GmbH, Wessling, Germany). PATIENTS AND METHODS: We analysed the data from 183 patients, including 13 children, undergoing extracorporeal shock wave lithotripsy (ESWL) for renal and ureteric calculi collected from a prospectively populated database. Outcomes were assessed by plain abdominal film of kidney, ureter and bladder and renal ultrasonography for radiopaque and computerized tomography for radiolucent stones 1 day after treatment and after 3 months. We analysed stone size and location before and after treatment, stone disintegration rate, retreatment rate, stone-free and residual fragment rates after 3 months, along with auxiliary procedures and complications. RESULTS: The mean (range) patient age was 48.6 (1.3-81.4) years, including 13 children with a mean (range) age of 8.4 (1.3-16.7) years, and 77% of the patients were male. In all, 46% of the calculi were localized in the kidney and 54% in the ureter. Renal stones were localized in the upper, middle and lower calyx and in the renal pelvis in 9, 29, 30 and 32% of patients, respectively. Ureteric stones were localized in the upper, mid- and distal ureter in 29, 19 and 52% of patients, respectively. The median (range) stone size before ESWL was 10 (4-25) mm in the kidney and 8 (4-28) mm in the ureteric calculi. The overall stone-free rate after 3 months was 91% (88% for renal and 93% for ureteric calculi); the mean number of sessions to achieve these rates was 1.3. Stone-free rates and the required number of sessions were determined only by stone size. In 7.1% of the patients (n = 13) post-interventional auxiliary procedures were necessary. We observed one perirenal haematoma as a major complication (0.5%), but this did not require any further therapy. CONCLUSIONS: Clinical stone-free rates with the Lithoskop are high and similar to those of other available systems, including the reference standard HM-3 lithotripter. Retreatment and complication rates are low, supporting the use of ESWL as first-line therapy for urinary calculi <10 mm, independent of stone location.

Intraoperative monitoring of bladder and internal anal sphincter innervation: a predictor of erectile function following low anterior rectal resection for rectal cancer? Results of a prospective clinical study.

BACKGROUND: The objective was to investigate whether two-dimensional intraoperative neuromonitoring (IONM) of pelvic autonomic nerves has the potential to predict erectile function (EF) following surgery for rectal cancer. METHODS: A consecutive series of 17 sexually active male rectal cancer patients undergoing IONM-based nerve-sparing low anterior rectal resection were evaluated prospectively. IONM was performed by electric stimulation of the pelvic splanchnic nerves with concomitant electromyography of the internal anal sphincter and cystomanometry. Sexual function was assessed using a validated questionnaire. RESULTS: The degree of agreement between electromyography-based and cystomanometry-based IONM with postoperative EF was moderate and good (κ = 0.43 and κ = 0.66). Combined assessment yielded the best agreement (κ = 0.76) with sensitivity of 90%, specificity of 86%, positive predictive value of 90%, negative predictive value of 86%, and overall accuracy of 88%, respectively, in terms of prediction of postoperative EF. CONCLUSION: The method may be suitable to predict male EF following rectal resection.

[Vaginal laser therapy-myths and facts]. / Vaginale Lasertherapie ­ Mythen und Fakten.

The current guideline "Female Urinary Incontinence" of the working group of scientific medical professional associations (AWMF) comprises a recommendation about the optional use of vaginal laser therapy in patients with mild to moderate stress urinary incontinence (SUI). Since to date there is no corresponding recommendation within the European Association of Urology (EAU) guidelines, the scientific evidence of the AWMF recommendation is evaluated. On the basis of limited data, both available laser systems (Erbium:YAG and CO2) seem to work equivalently in patients with mild SUI. The problematic comparability of studies with different definitions of incontinence, severity classifications, outcome parameters, and consideration of diverse etiological aspects is addressed. After thorough consideration of the available prognosticator research, a profile of an ideal laser candidate is developed for proper patient selection. This profile includes younger age, normal body mass index, sufficient estrogenization status, pure stress urinary incontinence due to urethral hypermobility, and urine loss of < 8 g during a 1 h pad test.

Urinary Incontinence and Pelvic Organ Prolapse in Women.

BACKGROUND: Pelvic floor disorders are common, especially in pregnancy and after delivery, in the postmenopausal period, and old age, and they can significantly impact on the patient's quality of life. METHODS: This narrative review is based on publications retrieved by a selective search of the literature, with special consideration to original articles and AWMF guidelines. RESULTS: Pelvic floor physiotherapy (evidence level [EL] 1), the use of pessaries (EL2), and local estrogen therapy can help alleviate stress/urge urinary incontinence and other symptoms of urogenital prolapse. Physiotherapy can reduce urinary incontinence by 62% during pregnancy and by 29% 3-6 months post partum. Anticholinergic and ß-sympathomimetic drugs are indicated for the treatment of an overactive bladder with or without urinary urge incontinence (EL1). For patients with stress urinary incontinence, selective serotonin-noradrenaline reuptake inhibitors can be prescribed (EL1). The tension-free tape is the current standard of surgical treatment (EL1); in an observational follow-up study, 87.2% of patients were satisfied with the outcome 17 years after surgery. Fascial reconstruction techniques are indicated for the treatment of primary pelvic organ prolapse, and mesh-based surgical procedures for recurrences and severe prolapse (EL1). CONCLUSION: Urogynecological symptoms should be specifically asked about by physicians of all relevant specialties; if present, they should be treated conservatively at first. Structured surgical techniques with and without mesh are available for the treatment of urinary incontinence and pelvic organ prolapse. Preventive measures against pelvic floor dysfunction should be offered during pregnancy and post partum.

Diagnosis and Therapy of Female Urinary Incontinence. Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry No. 015/091, January 2022): Part 2 with Recommendations on Interventional/Surgical Therapy of Overactive Bladder, Surgical Treatment of Stress Urinary Incontinence and Diagnosis and Therapy of Iatrogenic Urogenital Fistula.

Aim This completely revised interdisciplinary S2k-guideline on the diagnosis, therapy, and follow-up care of female patients with urinary incontinence (AWMF registry number: 015-091) was published in December 2021. This guideline combines and summarizes earlier guidelines such as "Female stress urinary incontinence," "Female urge incontinence" and "Use of Ultrasonography in Urogynecological Diagnostics" for the first time. The guideline was coordinated by the German Society for Gynecology and Obstetrics (Deutsche Gesellschaft für Gynäkologie und Geburtshilfe, DGGG) and the Working Group for Urogynecology and Plastic Pelvic Floor Reconstruction (Arbeitsgemeinschaft für Urogynäkologie und plastische Beckenbodenrekonstruktion e. V., AGUB). Methods This S2k-guideline was developed using a structured consensus process involving representative members from different medical specialties and was commissioned by the Guidelines Commission of the DGGG, OEGGG and SGGG. The guideline is based on the current version of the guideline "Urinary Incontinence in Adults" published by the European Association of Urology (EAU). Country-specific items associated with the respective healthcare systems in Germany, Austria and Switzerland were also incorporated. Recommendations The short version of this guideline consists of recommendations and statements on the surgical treatment of female patients with stress urinary incontinence and urge incontinence. Specific solutions for the diagnostic workup and treatment of uncomplicated and complicated urinary incontinence are discussed. The diagnostics and surgical treatment of iatrogenic urogenital fistula are presented.

Diagnosis and Therapy of Female Urinary Incontinence. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry No. 015/091, January 2022): Part 1 with Recommendations on Diagnostics and Conservative and Medical Treatment.

Aim This completely revised interdisciplinary S2k-guideline on the diagnosis, therapy, and follow-up care of female patients with urinary incontinence (AWMF registry number: 015-091) was published in December 2021. This guideline combines and summarizes earlier guidelines such as "Female stress urinary incontinence," "Female urge incontinence" and "Use of Ultrasonography in Urogynecological Diagnostics" for the first time. The guideline was coordinated by the German Society for Gynecology and Obstetrics (Deutsche Gesellschaft für Gynäkologie und Geburtshilfe, DGGG) and the Working Group for Urogynecology and Plastic Pelvic Floor Reconstruction (Arbeitsgemeinschaft für Urogynäkologie und plastische Beckenbodenrekonstruktion e. V., AGUB). Methods This S2k-guideline was developed using a structured consensus process involving representative members from different medical specialties and was commissioned by the Guidelines Commission of the DGGG, OEGGG and SGGG. The guideline is based on the current version of the guideline "Urinary Incontinence in Adults" published by the European Association of Urology (EAU). Country-specific items associated with the respective healthcare systems in Germany, Austria and Switzerland were also incorporated. Recommendations The short version of this guideline consists of recommendations and statements on the epidemiology, etiology, classification, symptoms, diagnostics, and treatment of female patients with urinary incontinence. Specific solutions for the diagnostic workup and appropriate conservative and medical therapies for uncomplicated and complication urinary incontinence are discussed.

Deregulation of E2-EPF ubiquitin carrier protein in papillary renal cell carcinoma.

Molecular pathways associated with pathogenesis of sporadic papillary renal cell carcinoma (PRCC), the second most common form of kidney cancer, are poorly understood. We analyzed primary tumor specimens from 35 PRCC patients treated by nephrectomy via gene expression analysis and tissue microarrays constructed from an additional 57 paraffin-embedded PRCC samples via immunohistochemistry. Gene products were validated and further studied by Western blot analyses using primary PRCC tumor samples and established renal cell carcinoma cell lines, and potential associations with pathologic variables and survival in 27 patients with follow-up information were determined. We show that the expression of E2-EPF ubiquitin carrier protein, which targets the principal negative regulator of hypoxia-inducible factor (HIF), von Hippel-Lindau protein, for proteasome-dependent degradation, is markedly elevated in the majority of PRCC tumors exhibiting increased HIF1α expression, and is associated with poor prognosis. In addition, we identified multiple hypoxia-responsive elements within the E2-EPF promoter, and for the first time we demonstrated that E2-EPF is a hypoxia-inducible gene directly regulated via HIF1. These findings reveal deregulation of the oxygen-sensing pathway impinging on the positive feedback mechanism of HIF1-mediated regulation of E2-EPF in PRCC.

Early vs delayed radical cystectomy for 'high-risk' carcinoma not invading bladder muscle: delay of cystectomy reduces cancer-specific survival.

OBJECTIVE: •To analyze the impact of a delayed radical cystectomy (rCx) and clinical variables on cancer-specific survival (CSS) in patients presenting 'high-risk' carcinoma not invading bladder muscle (nmiBCA). PATIENTS AND METHODS: •Between 1989 and 2006, 278 patients who presented 'high-risk' nmiBCA finally underwent rCx in our institution. •CSS was correlated with clinical variables such as the number of transurethral resections of the bladder (TURBs), interval between first TURB and rCx, adjuvant therapies, tumour upstaging at rCx, tumour stage and lymph node (LN) status. RESULTS: •The overall 5- and 10-year CSS was 82% and 76%, respectively. Significant correlations were found between the 5-year CSS and categorized number of TURBs (≤2 vs >2: 88% vs 71%; P= 0.001), interval between first TURB and rCx (≤4 months vs >4 months: 86% vs 77%; P= 0.04), adjuvant therapies (no vs yes: 86% vs 66%; P= 0.001), tumour upstaging at rCx (no vs yes: 89% vs 67%; P < 0.001), tumour stage at rCx (bladder confined vs non-confined: 88% vs 56%; P < 0.001) and LN status (no vs yes: 88% vs 36%; P < 0.001). •Multivariate analysis identified categorized number of TURBs (hazard ratio, HR, 0.14; 95% CI, 0.07-0.44; P < 0.001), categorized interval between first TURB and rCx (HR, 3.27; 95% CI, 1.24-8.59; P= 0.017), LN status (HR, 0.13; 95% CI, 0.06-0.26; P < 0.001) and tumour stage at rCx (HR, 0.49; 95% CI, 0.26-0.92; P= 0.03) as independent risk factors for CSS. CONCLUSION: •Delay of rCx in 'high-risk' nmiBCA deteriorates CSS and should be avoided. The number of TURBs and the interval between first TURB and rCx are causative factors for delayed rCx and are independently correlated with CSS.

Intraoperative peripheral frozen sections do not significantly affect prognosis after nerve-sparing radical prostatectomy for prostate cancer.

OBJECTIVE: • To determine the value of systematic intraoperative peripheral frozen sections (FS) with or without extended resection during nerve-sparing radical prostatectomy for prediction of biochemical recurrence (BCR) compared with inked surgical margins. PATIENTS AND METHODS: • Between 1999 and 2003, in a prospective study, multiple peripheral FS (median 14; range 5-20) were taken from the urethral stump, circumferentially from the bladder neck, and from the lateral pedicles in 200 consecutive bilateral nerve-sparing radical prostatectomies for clinically localized prostate cancer by a single surgeon. • Patients with stage pT3b or more and/or positive lymph nodes were excluded. • Of the 188 patients, 178 (94.7%) were followed over a median of 82 months (62-124). • BCR, defined as prostate-specific antigen (PSA) ≥ 0.2 ng/mL, was related to status of both, inked specimen margins and FS. RESULTS: • Of all 188 prostatectomy specimens, 49 (26.1%) had positive surgical margins (PSM); these were found posterolaterally in 15 (30.6%), apically in 13 (26.5%), basally in 10 (20.4%) and at multiple sites in 11 (22.4%) specimens. • Intraoperative peripheral FS were positive in 19 (10.7%) patients, including 6.2% at urethral stump, 3.3% at lateral pedicles and 1.1% at bladder neck. • In organ-confined disease, BCR-free survival was 93.3% (111/119) for patients with negative surgical margins (NSM) and 72% (18/25) for patients with PSM (inked specimen), but negative peripheral FS (P < 0.001). • Five- and 10-year BCR-free survival for NSM was 94.9% and 92.8%, for PSM with negative peripheral FS it was 75.3% and 70.6%, and for PSM with positive peripheral FS it was 62.5% and 62.5%, respectively. CONCLUSIONS: • Frozen section biopsies of peripheral resection margins during nerve-sparing radical prostatectomy are not reliable in predicting PSM. • Intraoperative achievement of a locally disease-free status, as monitored by negative circumferential intraoperative FS of peripheral margins, is not associated with a statistically significant BCR-free survival benefit compared with patients with negative surgical margins on the prostatectomy specimen. • Based on these findings, we do not recommend a routine of systematically taking intraoperative FS biopsies during nerve-sparing radical prostatectomy.

Confocal laser endomicroscopy for the diagnosis of urothelial bladder neoplasia: a technology of the future?

OBJECTIVE: To evaluate bladder urothelium by confocal laser endomicroscopy (CLE) and correlate microscopic findings with standard histopathology. PATIENTS AND METHODS: Fresh bladder urothelium tissue specimens were topically stained with acriflavine for instantaneous microscopic imaging. A single-line laser in a handheld CLE probe delivered an excitation wavelength of 488 nm providing a high resolution of 0.7 µm and an adjustable imaging depth of 0-250 µm. Resection specimens of 18 patients were investigated with 1000-fold magnification and ex vivo findings were compared with targeted histopathology (haematoxylin and eosin staining). RESULTS: Typical tumour growth patterns such as altered nuclear to cytoplasmic ratio, pseudopapillar tissue stratification and neoangiogenesis were readily visible. Nuclear and subnuclear architecture of healthy bladder tissue could be discriminated against neoplastic tissue. CONCLUSIONS: In addition to white light cystoscopy, CLE is a promising novel tool for the in vivo microscopic visualization of bladder cancer; first results of the present study show its potential to define microscopic characteristics of bladder cancer tissue. Further in vivo studies are necessary to determine sensitivity and specificity of the technique.

Perioperative morbidity and renal function in young and elderly patients undergoing elective nephron-sparing surgery or radical nephrectomy for renal tumours larger than 4 cm.

OBJECTIVE: To analyse renal function, perioperative morbidity and overall survival (OS) in patients aged <55 years compared with patients aged > 65 years treated by radical nephrectomy (RN) or elective nephron-sparing surgery (NSS) for renal tumours > 4 cm. PATIENTS AND METHODS: From our database, we identified 829 patients with renal tumours > 4 cm treated by either RN (n = 641) or NSS (n= 188) at our institution between 1981 and 2007. After excluding patients with imperative indication and metastases, we identified retrospectively 81 patients aged < 55 years (young patients) and 85 patients aged > 65 years (elderly patients) treated for renal tumours > 4 cm. In all, 36 and 33 patients underwent NSS and 45 and 52 patients underwent RN in the young and elderly group, respectively. Preoperative and periodically postoperative serum creatinin values were used to estimate glomerular filtration rate (GFR). Chronic kidney disease (CKD) was defined as GFR < 60 mL/min/1.73 m². Clinical characteristics, complications and renal function were compared between age groups and surgical approaches, and OS was estimated using the Kaplan-Meier method. RESULTS: The median (range) tumour size in young patients was larger compared with that of elderly patients, i.e. 6 (4.2-14.0) cm vs 5 (4.2-16.0) cm, with P < 0.001 considered to be statistically significant. The complication rates did not differ between the age groups (P = 0.656) or between NSS and RN in young (P = 0.095) or elderly patients (P = 0.277). Chronic kidney disease after RN or NSS occurred in 31.1% and 15.5% for young patients, respectively and in 50.9% and 24.2% in elderly patients, respectively, until last available follow-up which was obtained after a median (range) of 5.69 (0.1-19.2) years for young patients and 5.48 (0.8-18.1) years for elderly patients. Overall survival did not significantly differ between NSS vs RN in young (P = 0.655) and elderly patients (P = 0.058). CONCLUSION: Our findings suggest that performing NSS for tumours > 4 cm when feasible in young and carefully selected elderly patients is more beneficial for maintaining long-term renal function. Regardless of age, patients undergoing RN for renal tumours > 4 cm developed more new onsets of CKD than patients treated by elective NSS. The complication rate did not differ between the age groups or between types of surgery.