[Upper urinary tract urothelial cell carcinoma]. / Urothelkarzinom des oberen Harntrakts.

Upper urinary tract urothelial cell carcinoma (UTUC) is a rare entity. The incidence in Germany is approximately 2/100,000 with a ratio between women and men of 1:2.5. Most clinical signs are nonspecific, which is why early diagnosis is rarely successful. Computed tomography urography in combination with diagnostic ureterorenoscopy is currently the gold standard in the diagnostics of UTUC. Regarding surgical treatment, radical nephroureterectomy (RNU) with resection of a bladder cuff remains the method of choice, although the radical approach is developing towards laparoscopic/robotic or endourological procedures with preservation of kidney tissue. Due to the high recurrence rate (22-47%) of urothelial carcinoma inside the bladder, close follow-up after RNU is mandatory.

Preservation of the mesureter to reduce urinary complications: analysis of data from the observational Leipzig School MMR study.

OBJECTIVE: To evaluate the feasibility and effect of mesureteral preservation on urinary complications in the context of total mesometrial resection (TMMR), a surgical treatment for cervical cancer. DESIGN: Retrospective cohort study with historic control. SETTING: Single tertiary academic centre. POPULATION: Women older than 18 with primary cervical cancer staged FIGO IB1-IIB enrolled in the prospective Leipzig School MMR study and underwent total mesometrial resection (TMMR) without adjuvant radiation. METHOD: We retrospectively analysed 100 consecutive TMMR procedures which were performed for cancer of the uterine cervix and in which the mesureter was preserved (intervention group, 01/2014-06/2017). We compared this group with the previous 100 consecutive TMMRs, which were performed before the introduction of mesureteral preservation (control group, 09/2010-01/2014). MAIN OUTCOME MEASURES: The occurrence of urological and specifically ureteral complications. RESULTS: Mesureteral preservation was feasible and was associated with a significant decrease in ureteral complications (11% without mesureteral preservation versus 3% with mesureteral preservation, P = 0.049). Furthermore, we found a significant decrease in the number of postoperative percutaneous nephrostomies and re-operations (7% versus none, P = 0.014). There was also a trend towards a decrease in other urinary complications such as postoperative bladder atony and uretero-vaginal fistulas. CONCLUSION: The mesureter constitutes a convenient dissection plane enabling the preservation of lateral ureteral blood supply during TMMR. In our study, maintenance of mesureteral integrity was associated with a significant reduction in ureteral complications. Mesureteral preservation might also be useful in other types of pelvic surgeries that carry a high risk of ureteral damage. TWEETABLE ABSTRACT: Surgical preservation of the mesureter in cervical cancer patients was associated with a reduction in urinary complications.

[Robots in urology-an analysis of current and future devices]. / Der Roboter in der Urologie ­ eine Analyse aktueller und zukünftiger Gerätegenerationen.

The monopoly of robotic surgical devices of the last 15 years will end in 2019 when key patents of Intuitive Surgical expire. Thus, we can expect an interesting competitive situation in the coming years. Based on personal experience with robot-assisted surgery since 2001, we conducted a search of the current literature together with a search of relevant patents in this field. Finally, we visited the websites of manufacturers of existing and future robotic surgical devices with possible applications in urology. Such devices have to prove that they meet the high-quality standard of the current Da Vinci series (SI, X, XI). For this purpose, we propose to classify the main features of the different devices, such as type of console (closed/open), arrangement of robotic arms (single/multiple carts/attached to operating room table), type of three-dimensional videosystem (by mirror/ocular/using polarizing glasses) or degrees of freedom (DOF) of end effectors (5 vs. 7 DOF). In the meantime, there are also robotic systems used in endourology: Avicenna Roboflex® and the AquaBeam® system for robot-assisted aquablation therapy of the prostate. While Roboflex® improves the ergonomics of flexible ureteroscopy-similar to the Da Vinci robot, AquaBeam® may for the first time eliminate the surgeon, who might only be needed to manage severe postoperative bleeding.

[Anticorruption Act : A criminal proceedings prophylaxis for urologists]. / Antikorruptionsgesetz : Eine strafrechtliche Prophylaxe für den Urologen.

Since the introduction of the German Act to Combat Corruption in the Healthcare Sector concerns of fear and uncertainty are present. An elementary protection against criminal investigations can be achieved by complying with the physician professional law. Service contracts with the industry can be concluded if the interest in the service is reasonable and the payment is appropriate. There is a restrictive scale for clinical trials with already authorized products regarding any compensation granted which should correspond to the amount determined by the applicable elements of the German scale of medical fees (GOÄ). Invitations to academic training events can be accepted within an appropriate framework.

Live surgery: highly educational or harmful?

PURPOSE: Live surgery (LS) is considered a useful teaching opportunity. The benefits must be balanced with patient safety concerns. To evaluate the rate of complications of a series of urologic LS performed by experts during the Congress Challenge in Laparoscopy and Robotics (CILR). METHODS: We present a large, multi-institution, multi-surgeon database that derives from 12 CILR events, from 2004 to 2015 with a total of 224 cases. Radical prostatectomy (RP) was the most common procedure and a selection of complex cases was noted. The primary measure was postoperative complications and use of a Postoperative Morbidity Index (PMI) to allow quantitative weighing of postoperative complications. RESULTS: From 12 events, the number of cases increased from 11 in 2004 to 27 in 2015 and a total of 27 surgeons. Of 224 cases (164 laparoscopic and 60 robotic), there were 26 (11.6%) complications: 5 grade I, 5 grade II, 3 grade IIIa, 12 grade IIIb and 1 grade V, the latter from laparoscopic cystectomy. Analysis of PMI was 23 times higher from cystectomy compared to RP. CONCLUSIONS: In the setting of live surgery, the overall rate of complications is low considering the complexity of surgeries. The PMI is not higher in more complex procedures, whereas RP seems very safe.

Factors associated with non-participation and dropout among cancer patients in a cluster-randomised controlled trial.

We investigated the impact of demographic and disease related factors on non-participation and dropout in a cluster-randomised behavioural trial in cancer patients with measurements taken between hospitalisation and 6 months thereafter. The percentages of non-participation and dropout were documented at each time point. Factors considered to be potentially related with non-participation and dropout were as follows: age, sex, marital status, education, income, employment status, tumour site and stage of disease. Of 1,338 eligible patients, 24% declined participation at baseline. Non-participation was higher in older patients (Odds Ratio [OR] 2.1, CI: 0.6-0.9) and those with advanced disease (OR 2.0, CI: 0.1-1.3). Dropout by 6 months was 25%. Dropout was more frequent with increased age (OR 2.8, CI: 0.8-1.2), advanced disease (OR 3.0, CI: 1.0-1.2), being married (OR 2.4, CI 0.7-1.1) and less frequent with university education (OR 0.4, CI -1.3 to -0.8) and middle income (OR 0.4, CI -0.9 to -0.7). When planning clinical trials, it is important to be aware of patient groups at high risk of non-participation or dropout, for example older patients or those with advanced disease. Trial designs should consider their special needs to increase their rate of participation.

[Interstitial cystitis : Diagnosis and pharmacological and surgical therapy]. / Interstitielle Zystitis : Diagnostik, medikamentöse und operative Therapie.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic debilitating condition which generally has a severely negative impact on quality of life. An autoimmune genetic predisposition correlates with the theory of pathogenesis. Diagnosis requires history, diaries, physical examination, exclusion of other diseases, cystoscopy with or without hydrodistension and/or bladder biopsy. Novel biological markers are upcoming but not established. Behavioural, pharmacological oral and intravesical, interventional and surgical therapies with a wide range of reported success are available. A multimodal approach is recommended, although most of the therapeutic options lack a high degree of evidence.

[MRI/TRUS fusion-guided prostate biopsy : Value in the context of focal therapy]. / MRT/TRUS-fusionierte Biopsiesysteme : Stellenwert bei der fokalen Therapie des Prostatakarzinoms.

BACKGROUND: Several systems for MRI/TRUS fusion-guided biopsy of the prostate are commercially available. Many studies have shown superiority of fusion systems for tumor detection and diagnostic quality compared to random biopsy. The benefit of fusion systems in focal therapy of prostate cancer (PC) is less clear. OBJECTIVES: Critical considerations of fusion systems for planning and monitoring of focal therapy of PC were investigated. MATERIALS AND METHODS: A systematic literature review of available fusion systems for the period 2013-5/2016 was performed. A checklist of technical details, suitability for special anatomic situations and suitability for focal therapy was established by the German working group for focal therapy (Arbeitskreis fokale und Mikrotherapie). RESULTS: Eight fusion systems were considered (Artemis™, BioJet, BiopSee®, iSR´obot™ Mona Lisa, Hitachi HI-RVS, UroNav and Urostation®). Differences were found for biopsy mode (transrectal, perineal, both), fusion mode (elastic or rigid), navigation (image-based, electromagnetic sensor-based or mechanical sensor-based) and space requirements. DISCUSSION: Several consensus groups recommend fusion systems for focal therapy. Useful features are "needle tracking" and compatibility between fusion system and treatment device (available for Artemis™, BiopSee® and Urostation® with Focal One®; BiopSee®, Hitachi HI-RVS with NanoKnife®; BioJet, BiopSee® with cryoablation, brachytherapy). CONCLUSIONS: There are a few studies for treatment planning. However, studies on treatment monitoring after focal therapy are missing.

Morbidity and mortality after surgery for lower urinary tract symptoms: a study of 95 577 cases from a nationwide German health insurance database.

BACKGROUND: Little real-world data is available on the comparison of different methods in surgery for lower urinary tract symptoms due to benign prostatic obstruction in terms of complications. The objective was to evaluate the proportions of TURP, open prostatectomy (OP) and laser-based surgical approaches over time and to analyse the effect of approach on complication rates. METHODS: Using data of the German local healthcare funds (Allgemeine Ortskrankenkassen (AOK)), we identified 95 577 cases with a primary diagnosis of hyperplasia of prostate who received TURP, laser vaporisation (LVP), laser enucleation (LEP) of the prostate or OP between 2008 and 2013. Univariable logistic regression was used to analyse proportions of surgical approach over time, and the effect of surgical method on outcomes was analysed by means of multivariable logistic regression. RESULTS: The proportion of TURP decreased from 83.4% in 2008 to 78.7% in 2013 (P<0.001). Relative to TURP and adjusting for age, co-morbidities, AOK hospital volume, year of surgery and antithrombotic medication, OP had increased mortality (odds ratio (OR) 1.47, P<0.05), transfusions (OR 5.20, P<0.001) and adverse events (OR 2.17, P<0.001), and lower re-interventions for bleeding (OR 0.75, P<0.001) and long-term re-interventions (OR 0.55, P<0.001). LVP carried a lower risk of transfusions (OR 0.57, P<0.001) and re-interventions for bleeding (OR 0.76, P<0.001), but a higher risk of long-term re-interventions (OR 1.43, P<0.001). LEP had increased re-interventions for bleeding (OR 1.35, P<0.01). Complications were also dependent on age and co-morbidity. Limitations include the lack of clinical information and functional results. CONCLUSIONS: OP has the greatest risks of complication despite a low re-intervention rate. LVP demonstrated favourable results for transfusion and bleeding, but increased long-term re-interventions compared with TURP, while LEP showed increased re-interventions for bleeding. Findings support a careful indication and choice of method for surgery for LUTS, taking age and co-morbidities into account.

[Management of ureteral strictures and hydronephrosis]. / Management von Harnleiterstrikturen und Harnstauung.

Patients who develop hydronephrosis due to an acute cause often have colic-like pain but hydronephrosis secondary to a chronic cause is often asymptomatic. Ureteral obstruction can be due to a variety of intrinsic and extrinsic causes, such as trauma, radiation, iatrogenic injury, urolithiasis, malignancies and congenital causes. Management planning is dictated by the underlying cause, patient comorbidity and life expectancy. Malignant ureteral obstructions can be managed with segmental metal stents with advantages in the quality of life and provide an alternative to long-term treatment with a DJ stent. Endoscopic balloon dilatation and endoureterotomy are options for benign ureteral strictures up to 2 cm in length. For longer benign strictures there are a number of reconstructive techniques, which can also be performed by laparoscopic or robot-assisted approaches at specialized centers.

[Laparascopic radical prostatectomy]. / Laparoskopische radikale Prostatektomie.

BACKGROUND: Since its initial description 20 years ago, laparoscopic radical prostatectomy (LRP) is now a standard treatment option for localized prostate cancer. However, in recent years robot-assisted laparoscopic radical prostatectomy (RALP) has been gradually replacing LRP, despite high costs incurred with RALP. OBJECTIVES: The purpose of this work was to determine the oncological outcomes of LRP from selected series with a follow-up of around 10 years and to compare oncological and functional outcomes between LRP and RALP. MATERIAL AND METHODS: The outcomes of a case series of LRP with a median follow-up of at least 3 years were reviewed. In addition, the outcomes of comparative studies between LRP and RALP were reviewed. RESULTS: The first case series of LRP with follow-ups of 10 years after LRP are available and show favorable oncologic outcomes. Current data show that RALP offers superior functional results (recovery of erectile function) following bilateral nerve sparing when compared to LRP. CONCLUSION: The first review a few years ago showed comparable oncologic and functional outcomes between open prostatectomy, LRP, and RALP. Recent data from comparative studies show superiority of RALP over LRP for potency following bilateral nerve sparing. The potency outcomes between LRP and RALP are, however, similar following wide excision of both neurovascular bundles. Therefore, both treatment options can be recommended for the treatment of localized PC.

Circulating adipocyte fatty acid binding protein is increased in chronic and acute renal dysfunction.

BACKGROUND AND AIMS: The adipokine adipocyte fatty acid binding protein (AFABP) is positively associated with the development of the metabolic syndrome, diabetes mellitus, and cardiovascular disease. We hypothesized that AFABP also increases with deteriorating renal function. METHODS AND RESULTS: Serum AFABP levels were quantified by enzyme linked immunosorbent assay in 532 patients with chronic kidney disease (CKD) covering the whole spectrum of estimated glomerular filtration rate (eGFR) categories from G1 to G5 (study population 1). Furthermore, AFABP was measured in 32 patients before and within 30 h after elective unilateral nephrectomy, a model of acute kidney dysfunction (AKD) (study population 2). Moreover, circulating AFABP was investigated in rats undergoing bilateral nephrectomy (BNE) as compared to sham-operated animals. Median serum AFABP levels adjusted for age, gender, and body mass index significantly increased with increasing eGFR category (G1: 22.0 µg/l; G2: 34.6 µg/l; G3: 56.7 µg/l; G4: 95.2 µg/l; and G5: 173.9 µg/l). Furthermore, renal dysfunction remained positively associated with AFABP in multivariate analysis in this cohort. In patients undergoing unilateral nephrectomy, AFABP increased significantly after surgery (42.1 µg/l) as compared to pre-surgical values (29.3 µg/l). Furthermore, relative changes of post-to-pre-surgical AFABP levels were independently associated with relative changes of post-to-pre-surgical creatinine concentrations. After BNE in rats, AFABP increased significantly as compared to sham-operated animals. CONCLUSIONS: We show that AFABP is significantly elevated in CKD and AKD patients. Furthermore, measures of renal function are associated with circulating AFABP. Moreover, animal experiments indicate that AFABP levels strongly depend on renal function.

Psychological distress and adjustment to disease in patients before and after radical prostatectomy. Results of a prospective multi-centre study.

The aim of this prospective multi-centre study was to evaluate the level of psychological distress (PD) and adjustment to disease in patients who underwent radical prostatectomy. Furthermore, the impact of urinary incontinence and erectile dysfunction on PD was assessed. Anxiety, depression and PD were evaluated using the Hospital Anxiety and Depression Scale in 329 prostate cancer patients before surgery as well as 3, 6 and 12 months after surgery. These results were compared with those of a male German general population reference group. Adjustment to disease was assessed using the Perceived Adjustment to Chronic Illness Scale. Patients reported low levels of PD at all points of assessment similar to population norms of age-matched German men. Persistent PD was seen in about 8% of the patients and 20% had PD at least two of the measurement points. Relevant predictors for PD after surgery were urinary symptoms and baseline PD. Adjustment to disease was highest before surgery and had significantly reduced at 3 and 6 months after surgery. In general, men are resilient to the experience of localised prostate cancer and adjust well psychologically after surgery. However, between 8% and 20% of patients could possibly benefit from mental health support.

Value of endorectal magnetic resonance imaging at 3T for the local staging of prostate cancer.

PURPOSE: To assess the accuracy of endorectal 3 T magnetic resonance imaging (MRI) in detecting extracapsular extension (ECE) and seminal vesicle invasion (SVI) of prostate cancer (PCa). MATERIALS AND METHODS: 38 consecutive patients with biopsy-proven PCa underwent multiparametric endorectal MRI at 3 T prior to prostatectomy. Two readers (A with nine years of experience and B with four) used established criteria for ECE and SVI to diagnose the extent of local disease in six regions (apical, dorsolateral, basal; left and right each) with the highest chance of ECE. The standard of reference was provided by intraoperative frozen section analysis and prostatectomy specimens. RESULTS: Histopathology revealed ECE in 15 of the 222 regions (10 of 37 patients) and SVI in 8 of 74 potential regions (5 of 37 patients). The sensitivity, specificity, and accuracy in detecting ECE for reader A/B were 93%/67%, 92%/95% and 92%/93% per region and 90%/80%, 74%/82% and 78%/81% per patient, respectively. The corresponding values for the detection of SVI were 80%/100%, 96%/99% and 95%/97%, respectively. CONCLUSION: Endorectal 3 T MRI is a highly reliable noninvasive technique for the local staging of PCa. KEY POINTS: ► Endorectal 3 T MRI provided high accuracy for the local staging of prostate cancer. ► The sensitivity in detecting extracapsular tumor growth per patient was 80% or higher. ► The specificity in detecting extracapsular extension (pT3 stage) was good.

Weight loss surgery improves the metabolic status in an obese rat model but does not affect bladder fibrosis associated with high fat diet feeding.

BACKGROUND: Bladder dysfunction has one of the highest prevalences as a comorbidity of obesity in industrialized countries. The aetiopathogenesis of obesity-associated bladder dysfunction is still obscure, but there is growing evidence that general metabolic changes in obese patients may be in part responsible. As demonstrated recently, high fat diet (HFD) significantly alters the protein expression in the urinary bladder, activates multiple signalling pathways associated with cell survival and inflammation and ultimately provokes bladder fibrosis in an obese rat model. The study aimed to elucidate the role of matrix metalloproteases (MMPs) and their specific tissue inhibitors of metalloproteases (TIMPs) in obesity-related bladder extracellular matrix (ECM) remodelling and the effect of weight loss surgery via sleeve gastrectomy (SG) on phenotype and molecular parameters. METHODS: Twenty-four male Sprague-Dawley rats were used for (i) characterization of the HFD phenotype and (ii) evaluation of alterations following SG. Metabolic status, the degree of bladder fibrosis and tissue expression and activity of MMP2, MMP9, MMP14, TIMP1 and TIMP2 were analysed by immunohistochemistry, enzyme-linked immunosorbent assay and activity assays. Statistical differences were calculated by analysis of variance or independent Student's t-test. A P-value <0.05 was considered statistically significant. RESULTS: In HFD rats, we found significant alterations in lipid metabolism, fat mass, free fatty acid profile, insulin resistance and inflammatory markers. Voided volume was significantly decreased, and bladder showed marked fibrosis. MMPs and TIMPs were differentially regulated depending on animal status (controls, chow diet, HFD, and SG- and sham-operated animals) in both urothelium and detrusor smooth muscle. Although animal weight and most metabolic parameters were positively affected by SG, bladder fibrosis persisted. The limitations of this study were 1 month follow-up and lack of direct measurement of bladder function. CONCLUSIONS: Early diagnosis of the bladder dysfunction associated with obesity is essential to allow targeted early intervention, that is, before manifestation of potentially irreversible ECM fibrotic alterations.

Analysis of the pentafecta learning curve for laparoscopic radical prostatectomy.

PURPOSE: Laparoscopic radical prostatectomy (LRP) has a long learning curve; however, little is known about the pentafecta learning curve for LRP. We analysed the learning curve for a fellowship trained surgeon with regard to the pentafecta with up to 6-year follow-up. METHODS: A retrospective review was performed in 550 cases, by dividing these cases into 11 groups of 50 patients. Outcomes analysed were the following: (1) the pentafecta (complication rate, positive surgical margin (PSM) rate, continence, potency and biochemical recurrence); (2) operative time and blood loss; and (3) overall pentafecta attainment. RESULTS: The mean complication rate for the entire series was 9 %; this plateaued after 150 cases. The overall PSM rate for the series was 23.5 %, 16.3 % for pT2 and 40.5 % for pT3. PSM plateaued after 200 cases. Excluding the first 100 cases, the overall PSM rate for pT2 was 10.9 % and 37.8 % for pT3. The continence rate stabilised after approximately 250 cases. The rate of male sling/artificial urinary sphincter plateaued after 200 cases. The potency learning curve continues to improve after 250 cases of nerve-sparing (ns) endoscopic extraperitoneal radical prostatectomy (EERPE) as does the pentafecta learning curve which closely follows the pattern of the potency learning curve. The last group of nsEERPE achieved pentafecta in 63 %. CONCLUSION: This study shows multiple learning curves: an initial for peri-operative outcomes, then stabilisation of oncologic outcomes and the final for stabilisation of functional outcomes. In this series over 250 cases were required to achieve the learning curve.

[Photodynamic therapy of bladder cancer. A new option]. / Die photodynamische Therapie des Harnblasenkarzinoms. Eine neue Option.

BACKGROUND: Bladder cancer (BCa) is the third most common tumor in Germany. Currently, resection therapy for superficial BCa (Ta, CIS) includes photodynamic diagnostics (PDD) using HEXVIX® for improved assessment of tumor spread. Trials using these photosensitizers for photodynamic therapy (PDT) showed only limited success. Especially low tissue penetration due to short-wave excitation was a limiting factor. METHODS: This study which was funded by the German Research Foundation (DFG) examined the feasibility of the novel photosensitizer tetrahydroporphyrin-tetratosylate (THPTS) for PDT in a rat bladder cancer model. RESULTS: As THPTS is very effectively excitable at a near infrared wavelength of 760 nm it is within the so-called phototherapeutic window and allows tissue penetration of up to 15 mm. Thus THPTS can also be used for PDT of larger, solid tumors as was previously demonstrated for other tumor entities. Therefore, effective treatment of even muscle-invasive bladder cancer (≥T2) may become an option using THPTS. In this current study the effectiveness and safety of THPTS-PDT was examined in an orthotopic bladder cancer rat model.

[Proteome-based diagnostic and prognostic biomarkers of prostate cancer]. / Proteombasierte diagnostische und prognostische Biomarker beim Prostatakarzinom.

BACKGROUND: Due to comprehensive PSA screening, the incidence for prostate cancer (PCa) is rising. Therefore, there is an urgent need for improved PCa diagnostics and prognostic tools to differentiate between insignificant and aggressive, fast growing tumors. METHODS: With the proteome-based method presented here, we were able to distinguish PCa from BPH, chronic prostatitis and healthy controls with 83 % sensitivity and 67 % specificity. Furthermore, the methods discerned advanced PCa from local, organ-confined PCa in a group of patients with gleason score 7 (80 % sensitivity, 82 % specificity). RESULTS: Our proteomic approach is based on the analysis of low molecular weight polypeptides, identified as the endpoint of the naturally occuring liquefaction cascade in seminal plasma. For the first time using seminal plasma as a source, we analysed a complex network of interacting proteases and specific inhibitors, reflecting tumor biology specificity. Our diagnostic and prognostic tool is robust and easy to handle, and therefore it is well suitable for the laboratory and medical practice.