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.

[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.

[Continence and pelvic floor centers-Meaningful certification requirements?] / Kontinenz- und Beckenbodenzentren ­ sinnvolle Zertifizierungsvorgaben?

As a consequence of the demographic change, the prevalence of female and male bladder and bowel dysfunction, functional pelvic floor disorders and pelvic organ prolapse are steadily increasing. Continence and pelvic floor centers are interdisciplinary facilities that focus on these functional disorders, including malformations, tumors and functional disorders resulting from neurogenic diseases, injuries or surgery. The affected patient clientele includes children, women, and men of all ages. The certification is carried out by the accredited certification company CERT iQ Certification Services. In addition to structural requirements, personal quality criteria are also implemented in the novel harmonized and standardized certification system. The assessment of treatment quality is also a component of the procedure, although it is currently limited to the midurethral sling tracer procedure for the treatment of female stress urinary incontinence. Regarding the other conservative and surgical treatment options for pelvic floor, bladder and bowel functional disorders, no quality of outcome has so far been recorded. Internationally recognized and validated questionnaires to assess preoperative and postoperative quality of life would be valuable tools to define the quality of treatment and outcome. Similarly, supplementary thresholds should be established for complication rates and quality of the success of treatment to identify centers with high expertise. In this context, it is crucial to consider the individual complexity of the patient groups and to distinguish between primary and recurrent interventions.

Continent Anal Urinary Diversion in Classic Bladder Exstrophy: 45-Year Experience.

OBJECTIVE: To evaluate the long-term outcomes in patients with classic bladder exstrophy and continent anal urinary diversion (CAD) for continence, upper urinary tract status, secondary malignancies, and sexual function. PATIENTS AND METHODS: The medical records of 82 exstrophy patients having undergone CAD in our department between 1970 and 2015 were reviewed. Patients were invited for follow-up examinations and asked to complete validated questionnaires relating to sexual function. RESULTS: Thirty-two of 57 eligible patients with a median follow-up of 23.9 years were included in the study. Ninety-seven percent of patients were fully continent during daytime. Upper urinary tract and renal function remained stable in 75% and 87%, respectively. Five patients developed secondary malignancies originating from the rectal reservoir. Forty-one percent received prophylactic alkaline substitution. Sexual function as measured by the Female Sexual Function Index and the International Index on Erectile Function was negatively affected in all domains in both genders. Eighty-six percent of patients had a stable relationship and 35% were married. Five women conceived a total of 6 healthy children. Paternity rate was 40%. CONCLUSION: CAD constitutes an effective treatment option with acceptable long-term outcomes in exstrophy patients in whom all attempts at restoring the lower urinary tract have failed. Long-term follow-up of the upper urinary tract, assessment of acid-base balance, and endoscopy of the rectosigmoid reservoir are paramount for the safety of this type of management. Evaluation of sexual dysfunction should be an active part of follow-up.

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.

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.

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.

Concomitant Gleason Score ≥ 7 prostate cancer is an independent prognosticator for poor survival in nonmetastatic bladder cancer patients undergoing radical cystoprostatectomy.

PURPOSE: In bladder cancer (BCa) patients undergoing radical cystoprostatectomy (RCPx), concomitant prostate cancer (PCa) is a common finding. Up to now there is no clear evidence to suggest that concomitant PCa is a predictor of outcome in these patients. Aim of this study was to assess incidence and clinicopathologic characteristics of concomitant PCa in RCPx specimen and correlate it to survival parameters from a single-centre material over two decades. METHODS: All men who had undergone RCPx for BCa at our institution between 1994 and 2013 were included in this study. Clinicopathologic parameters for BCa and PCa were evaluated and correlated with outcome parameters. Survival analysis was performed for the subgroup of nonmetastatic organ-confined BCa to evaluate the role of concomitant Gleason Score (GS) ≥7 PCa. RESULTS: Of 945 men who had undergone RCPx for BCa, concomitant PCa was present in 237 patients (25.1 %). There was a significant increase in PCa incidence from 18.9 to 32.3 % between 1994 and 2013 (p = 0.009). Concomitant PCa represented a more aggressive phenotype at the end of the study (p = 0.037). In nonmetastatic organ-confined BCa, concomitant GS ≥7 PCa (HR 3.09; p = 0.0001) and age > 68 (HR 1.80; p = 0.0004) were independent negative predictors for overall survival. CONCLUSIONS: Concomitant PCa in RCPx specimen of BCa patients is a common finding. The incidence of concomitant PCa has significantly increased within 2 decades, presenting a more aggressive phenotype. Age and in particular concomitant GS ≥7 PCa are independent prognosticators for poor survival in patients with nonmetastatic organ-confined BCa.

Self-adjuvanted mRNA vaccination in advanced prostate cancer patients: a first-in-man phase I/IIa study.

BACKGROUND: CV9103 is a prostate-cancer vaccine containing self-adjuvanted mRNA (RNActive®) encoding the antigens PSA, PSCA, PSMA, and STEAP1. This phase I/IIa study evaluated safety and immunogenicity of CV9103 in patients with advanced castration-resistant prostate-cancer. METHODS: 44 Patients received up to 5 intra-dermal vaccinations. Three dose levels of total mRNA were tested in Phase I in cohorts of 3-6 patients to determine a recommended dose. In phase II, 32 additional patients were treated at the recommended dose. The primary endpoint was safety and tolerability, the secondary endpoint was induction of antigen specific immune responses monitored at baseline and at weeks 5, 9 and 17. RESULTS: The most frequent adverse events were grade 1/2 injection site erythema, injection site reactions, fatigue, pyrexia, chills and influenza-like illness. Possibly treatment related urinary retention occurred in 3 patients. The recommended dose was 1280 µg. A total of 26/33 evaluable patients treated at 1280 µg developed an immune response, directed against multiple antigens in 15 out of 33 patients. One patient showed a confirmed PSA response. In the subgroup of 36 metastatic patients, the Kaplan-Meier estimate of median overall survival was 31.4 months [95 % CI: 21.2; n.a]. CONCLUSIONS: The self-adjuvanted RNActive® vaccine CV9103 was well tolerated and immunogenic. The technology is a versatile, fast and cost-effective platform allowing for creation of vaccines. The follow-up vaccine CV9104 including the additional antigens prostatic acid phosphatase (PAP) and Muc1 is currently being tested in a randomized phase IIb trial to assess the clinical benefit induced by this new vaccination approach. TRIAL REGISTRATION: EU Clinical Trials Register: EudraCT number 2008-003967-37, registered 27 Jan 2009.

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.

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.

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.

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.

Functional analysis of elective nephron-sparing surgery vs radical nephrectomy for renal tumors larger than 4 cm.

OBJECTIVE: To preserve renal function, nephron sparing surgery (NSS) for renal tumors should be performed. Little is known about perioperative morbidity and long-term functional outcome of patients after elective NSS compared with radical nephrectomy (RN) in renal tumors >4 cm. MATERIALS AND METHODS: Eight-hundred twenty-nine patients were treated with either RN (n = 641) or NSS (n = 188) for renal tumors >4 cm. After pairing the cohort for age, grading, TNM, size, gender, and preoperative renal function and excluding patients with imperative indication and metastases, 247 patients remained for functional analysis. Serum creatinine (SCr) values were used to estimate glomerular filtration rate (eGFR) via Modification of Diet in Renal Disease. Chronic kidney disease (CKD) was defined as eGFR <60 mL/min/1.73 m(2) and regression analyses were used to identify clinical risk factors for CKD and perioperative complications stratified by the Clavien-Dindo score. RESULTS: The Charlson comorbidity index was similar between patients undergoing NSS (n = 101) and RN (n = 146) (P = .583). The complication rates did not differ significantly between both groups (P = .091). Age (OR 0.94, P = .009), ASA score 3+4 (OR 3.55, P = .004), RN (OR 10.75, P < .001), and preoperative eGFR (OR 1.06, P < .001) were independent risk factors for developing CKD postoperatively, whereas tumor size had no impact (OR 1.01, P = .245). Overall survival was comparable between the groups (P = .896). CONCLUSION: Although overall survival was similar, patients undergoing RN for renal tumors >4 cm had a significantly higher risk of developing CKD than patients treated with NSS. Complication rate did not differ significantly between both groups, even for tumors >7 cm. Our findings support elective NSS for tumors >4 cm, whenever NSS is technically feasible for maintaining renal function.

Short-term functional and oncologic outcomes of nephron-sparing surgery for renal tumours ≥ 7 cm.

BACKGROUND: Nephron-sparing surgery (NSS) for renal tumours preserves renal function and has become the standard approach for small renal tumours. Little is known about perioperative and oncologic outcomes of patients following NSS in renal tumours ≥ 7 cm in the presence of a healthy contralateral kidney. OBJECTIVE: To analyse oncologic outcomes and perioperative morbidity in patients treated by NSS for renal tumours ≥ 7 cm. DESIGN, SETTING, AND PARTICIPANTS: In total, 5767 patients were treated for renal tumours at two institutions from 1984 to 2009. In 91 patients, elective NSS was performed for renal tumours ≥ 7 cm. MEASUREMENTS: Complication rates were assessed in detail and stratified using the Clavien-Dindo score (CDS). Oncologic outcomes for overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Logistic regression analysis was used to identify clinical risk factors for complications and prognosticators that have an oncologic impact on OS. RESULTS AND LIMITATIONS: The median follow-up was 28 mo (range: 1-247 mo). Twenty-seven patients (29.6%) had perioperative complications and, of these, 89.1% had CDS grade 1 and 2. Twenty-seven percent of the 91 patients had benign lesions. Seven patients (10.6%) died from cancer-related causes. The 5- and 10-yr rates for OS, CSS, and PFS were 88% and 64%, 97% and 83%, and 91% and 78%, respectively. None of the analysed parameters had an impact on morbidity or OS in the univariate analysis. Limitations of this study were its retrospective nature and the relatively short follow-up period for oncologic outcome. CONCLUSIONS: NSS for renal tumours ≥ 7 cm can be performed with acceptable complication rates and with oncologic outcomes comparable to radical nephrectomy studies. Our findings support NSS whenever technically feasible to reduce the loss of renal function.