Modelling the biodistribution of inhaled gold nanoparticles in rats with interspecies extrapolation to humans.

The increasing intentional and non-intentional exposure to nanoparticles (NPs) has raised the interest concerning their fate and biodistribution in the body of animals and humans after inhalation. In this context, Physiologically Based (pharmaco)Kinetic (PBK) modelling has emerged as an in silico approach that simulates the biodistribution kinetics of NPs in the body using mathematical equations. Due to restrictions in data availability, such models are first developed for rats or mice. In this work, we present the interspecies extrapolation of a PBK model initially developed for rats, in order to estimate the biodistribution of inhaled gold NPs (AuNPs) in humans. The extrapolation framework is validated by comparing the model results with experimental data from a clinical study performed on humans for inhaled AuNPs of two different sizes, namely 34 nm and 4 nm. The novelty of this work lies in the extrapolation of a PBK model for inhaled AuNPs to humans and comparison with clinical data. The extrapolated model is in good agreement with the experimental data, and provides insights for the mechanisms of inhaled AuNP translocation to the blood circulation, after inhalation. Finally, the biodistribution of the two sizes of AuNPs in the human body after 28 days post-exposure is estimated by the model and discussed.

Modeling of clearance, retention, and translocation of inhaled gold nanoparticles in rats.

Objective: The increasing exposure to gold nanoparticles (AuNPs), due to their wide range of applications, has led to the need for thorough understanding of their biodistribution, following exposure. The objective of this paper is to develop a PBK model in order to study the clearance, retention and translocation of inhaled gold nanoparticles in rats, providing a basis for the understanding of the absorption, distribution, metabolism and elimination (ADME) mechanisms of AuNPs in various organs.Materials and methods: A rat PBK computational model was developed, connected to a detailed respiratory model, including the olfactory, tracheobronchial, and alveolar regions. This model was coupled with a Multiple Path Particle Dosimetry (MPPD) model to appropriately simulate the exposure to AuNPs. Three existing in vivo experimental datasets from scientific literature for the biodistribution of inhaled AuNPs for different AuNP sizes and exposure scenarios were utilized for model calibration and validation.Results and Discussion: The model was calibrated using two individual datasets for nose only inhaled and intratracheally instilled AuNPs, while an independent dataset for nose only inhaled AuNPs was used as external validation. The overall fitting over the three datasets was proved acceptable as shown by the relevant statistical metrics. The influence of several physiological parameters is also studied via a sensitivity analysis, providing useful insights into the mechanisms of NP pharmacokinetics. The key aspects of the inhaled AuNPs biodistribution are discussed, revealing the key mechanisms for the AuNPs absorption routes, the AuNP uptake by secondary organs and the influence of the AuNP size on the translocation from the lungs to blood circulation.Conclusions: The model results together with the model sensitivity analysis clarified the key mechanisms for the inhaled AuNPs biodistribution to secondary organs. It was observed that nose-only inhaled AuNPs of smaller size can enter the blood circulation through secondary routes, such as absorption through the gastrointestinal (GI) lumen, showing that such translocations should not be underestimated in biodistribution modelling. Finally, the computational framework presented in this study can be used as a basis for a more wide investigation of inhaled nanoparticles biodistribution, including interspecies extrapolation of the resulting PBK model for the inhalation and subsequent biodistribution of AuNPs in humans.

Adherence to the EAU guideline recommendations for systemic chemotherapy in penile cancer: results of the E-PROPS study group survey.

OBJECTIVES: To validate the adherence of urologists to chemotherapy recommendations given in the EAU guidelines on PeCa. The European Association of Urology (EAU) guidelines on penile cancer (PeCa) are predominantly based on retrospective studies with low level of evidence. MATERIALS AND METHODS: A 14-item-survey addressing general issues of PeCa treatment was developed and sent to 45 European hospitals. 557 urologists participated in the survey of which 43.5%, 19.3%, and 37.2% were in-training, certified, and in leading positions, respectively. Median response rate among participating departments was 85.7% (IQR 75-94%). Three of 14 questions addressed clinical decisions on neoadjuvant, adjuvant, and palliative chemotherapy. Survey results were analyzed by bootstrap-adjusted multivariate logistic-regression-analysis to identify predictors for chemotherapy recommendations consistent with the guidelines. RESULTS: Neoadjuvant, adjuvant, and palliative chemotherapy was recommended according to EAU guidelines in 21%, 26%, and 48%, respectively. For neoadjuvant chemotherapy, urologists holding leading positions or performing chemotherapy were more likely to recommend guideline-consistent treatment (OR 1.85 and 1.92 with p(bootstrap) = 0.007 and 0.003, respectively). Supporting resources (i.e., guidelines, textbooks) were used by 23% of survey participants and significantly improved consistency between treatment recommendations and Guideline recommendations in all chemotherapy settings (p(bootstrap) = 0.010-0.001). Department size and university center status were no significant predictors for all three endpoints. CONCLUSIONS: In this study, we found a very low rate of adherence to the EAU guidelines on systemic treatment for PeCa. Further investigations are needed to clarify whether this missing adherence is a consequence of limited individual knowledge level or of the low grade of guideline recommendations.

EAU-ESMO consensus statements on the management of advanced and variant bladder cancer-an international collaborative multi-stakeholder effort: under the auspices of the EAU and ESMO Guidelines Committees†.

BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial. OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management. DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts before voting during a consensus conference. SETTING: Online Delphi survey and consensus conference. PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus). RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these, 33 (28%) statements achieved level 1 consensus and 49 (42%) statements achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease and the evolving role of checkpoint inhibitor therapy in metastatic disease. CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time where further evidence is available to guide our approach.

Laparoscopic radical nephrectomy with inferior vena cava thrombectomy: highlight of key surgical steps.

OBJECTIVE: Vascular involvement in the form of renal vein (RV) or inferior vena cava (IVC) thrombus can be seen in 4-10% of patients presented with RCC. In patients without presence of metastasis, surgical treatment in the form of radical nephrectomy remains the treatment of choice with 5-year survival rates of 45-70%. Open surgery is still the first treatment option of choice at the moment for RCC patients with IVC thrombus. MATERIALS AND METHODS: In our study, we are reporting a case of patient with RCC and level I IVC thrombus treated with laparoscopy. Our patient is a 72 years old man with underlying co-morbidity of hypertension and chronic kidney disease (CKD) presented with right-sided RCC. The CT scan done showed a large right renal upper pole tumor measuring 8.4x5.2cm with level I IVC thrombus (Figure-1). There were no regional lymphadenopathy and the staging scans were negative. RESULTS: The operative time was 124 minutes and blood loss was minimal. The patient was progressed to diet on POD 1 with bowel movement on POD 2. There was no significant change in the pre and post-operative glomerular filtration rate (GFR). The surgical drain was removed on POD2. The patient was discharged well on POD 5. There were no perioperative complications. The pathology was pT3bN0M0 Fuhrman grade II clear cell RCC. CONCLUSIONS: As a conclusion, laparoscopic radical nephrectomy and IVC thrombectomy is a complex and technically demanding surgery. With advancement of surgical skills as well as technology, more cases of minimally invasive laparoscopic radical nephrectomy and IVC thrombectomy can performed to improve the perioperative outcomes of carefully selected patients in a high volume center.

Impact of perioperative chemotherapy on survival in patients with advanced primary urethral cancer: results of the international collaboration on primary urethral carcinoma.

BACKGROUND: To investigate the impact of perioperative chemo(radio)therapy in advanced primary urethral carcinoma (PUC). PATIENTS AND METHODS: A series of 124 patients (86 men, 38 women) were diagnosed with and underwent surgery for PUC in 10 referral centers between 1993 and 2012. Kaplan-Meier analysis with log-rank testing was used to investigate the impact of perioperative chemo(radio)therapy on overall survival (OS). The median follow-up was 21 months (mean: 32 months; interquartile range: 5-48). RESULTS: Neoadjuvant chemotherapy (NAC), neoadjuvant chemoradiotherapy (N-CRT) plus adjuvant chemotherapy (ACH), and ACH was delivered in 12 (31%), 6 (15%) and 21 (54%) of these patients, respectively. Receipt of NAC/N-CRT was associated with clinically node-positive disease (cN+; P = 0.033) and lower utilization of cystectomy at surgery (P = 0.015). The objective response rate to NAC and N-CRT was 25% and 33%, respectively. The 3-year OS for patients with objective response to neoadjuvant treatment (complete/partial response) was 100% and 58.3% for those with stable or progressive disease (P = 0.30). Of the 26 patients staged ≥cT3 and/or cN+ disease, 16 (62%) received perioperative chemo(radio)therapy and 10 upfront surgery without perioperative chemotherapy (38%). The 3-year OS for this locally advanced subset of patients (≥cT3 and/or cN+) who received NAC (N = 5), N-CRT (N = 3), surgery-only (N = 10) and surgery plus ACH (N = 8) was 100%, 100%, 50% and 20%, respectively (P = 0.016). Among these 26 patients, receipt of neoadjuvant treatment was significantly associated with improved 3-year relapse-free survival (RFS) (P = 0.022) and OS (P = 0.022). Proximal tumor location correlated with inferior 3-year RFS and OS (P = 0.056/0.005). CONCLUSION: In this series, patients who received NAC/N-CRT for cT3 and/or cN+ PUC appeared to demonstrate improved survival compared with those who underwent upfront surgery with or without ACH.

Influence of age on false positive rates of urine-based tumor markers.

INTRODUCTION: Several influencing factors on false positive rates (FPRs) of urine-based tumor markers in the detection of urothelial cancer (UC) have been identified. We evaluated age as a possible influencing factor. METHODS: Urinary cytology (Cyt), UroVysion (FISH), ImmunoCyt (uCyt+) and NMP22 were determined in 1,554 patients suspicious for UC of the bladder before cystoscopy and in case of cancer detection before TURB. Additionally, upper urinary tract imaging was performed. Maker sensitivity, specificity and FPRs were evaluated in the entire cohort and in subgroups divided by age into <50, ≥ 50-70 and ≥ 70 years. Contingency tables and the Cochrane Armitage tests were used for statistical comparisons. RESULTS: UC was found in 377 and no UC in 1,177 (75 %) patients. A total of 336 patients were diagnosed with UC of the bladder and 41 with UC of the upper urinary tract. Overall sensitivity and specificity for Cyt were 82 and 82 %: for FISH, 73 and 79 % and for uCyt+, 79 and 75 %, respectively. For NMP22, regardless of the exclusion criteria they were 72 and 34 % and after exclusion of urinary tract infection (UTI) or prior to manipulation 46 and 86 %, respectively. Significantly higher FPRs were found with increasing age for Cyt (p = 0.001), a trend to higher FPRs for uCyt+ (p = 0.11) and almost no difference for FISH (p = 0.63). For NMP22, differences became significant after exclusion of patients with UTI or prior manipulation (p = 0.02). CONCLUSIONS: The results of the present study give evidence that false positive rates of Cyt and NMP22 increase with age indicating that age should be respected for their correct interpretation.

Cost effective laparoendoscopic single-site surgery with a reusable platform.

BACKGROUND AND OBJECTIVES: Many disposable platforms have been applied in laparoendoscopic single-site surgery (LESS). Besides technical issues, cost is one of the limiting factors for its widespread acceptance. The current study describes the first completely reusable LESS-platform. METHODS: We performed LESS-procedures in 52 patients including nephrectomy (18), adrenalectomy (2), partial nephrectomy (3), pyeloplasty (4), renal cyst ablation (4), pelvic lymphadenectomy (15), and lymphocele ablation (6). All procedures were conducted using a novel reusable single-port device (X-Cone, Karl-Storz) with a simplified set of instruments. We obtained perioperative and demographic data, including a visual analogue pain scale (VAS), and a complication reporting system based on Clavien grading. RESULTS: Mean age was 50.04 y. Conversion to standard laparoscopy was necessary in 3 cases and addition of a needlescopic instrument in 6 cases. There was no open conversion. Intra- and postoperative complications occurred in 3 (Clavien II in 2 and III in 1) cases. Mean operative time was 110, 90, and 89 min, and hospital stay was 4.9, 3.1, and 3.6 d for nephrectomy, pelvic lymphadenectomy, and pyeloplasty, respectively. Mean VAS was 2.13, 1.07, and 1.5 while blood loss was 81.3 mL, 25.67 mL, and 17.5 mL, respectively. Mean lymph node yield was 15 (range, 8 to 21). CONCLUSIONS: A completely reusable LESS-platform is applicable to various uses in urology, yielding favorable functional and cosmetic results. Reusable materials are useful to reduce the cost of LESS, further increasing its acceptance. LESS with a completely reusable platform is more cost effective than standard laparoscopy.

A structure-activity approach towards the toxicity assessment of multicomponent metal oxide nanomaterials.

The increase of human and environmental exposure to engineered nanomaterials (ENMs) due to the emergence of nanotechnology has raised concerns over their safety. The challenging nature of in vivo and in vitro toxicity assessment methods for ENMs, has led to emerging in silico techniques for ENM toxicity assessment, such as structure-activity relationship (SAR) models. Although such approaches have been extensively developed for the case of single-component nanomaterials, the case of multicomponent nanomaterials (MCNMs) has not been thoroughly addressed. In this paper, we present a SAR approach for the case metal and metal oxide MCNMs. The developed SAR framework is built using a dataset of 796 individual toxicity measurements for 340 different MCNMs, towards human cells, mammalian cells, and bacteria. The novelty of the approach lies in the multicomponent nature of the nanomaterials, as well as the size, diversity and heterogeneous nature of the dataset used. Furthermore, the approach used to calculate descriptors for surface loaded MCNMs, and the mechanistic insight provided by the model results can assist the understanding of MCNM toxicity. The developed models are able to correctly predict the toxic class of the MCNMs in the heterogeneous dataset, towards a wide range of human cells, mammalian cells and bacteria. Using the abovementioned approach, the principal toxicity pathways and mechanisms are identified, allowing a more holistic understanding of metal oxide MCNM toxicity.

Early sacral neuromodulation prevents urinary incontinence after complete spinal cord injury.

BACKGROUND: The study aim was to investigate potential influences on human nerves and pelvic organs through early implantation of bilateral sacral nerve modulators (SNMs) in complete spinal cord injury (SCI) patients during the acute bladder-areflexia phase. METHODS: Ten patients with neurologically-confirmed complete spinal cord lesions (SCLs) were provided with bilateral SNMs during the phase of atonic-detrusor muscle. Modulation was achieved by two electrodes implanted into each S(3)-foramen. Six patients declined and served as controls. The mean follow-up was 26.2 months. RESULTS: Videourodynamics (VU) confirmed detrusor acontractility, resulting in urinary continence as well as significant reductions in urinary tract infections (UTIs). Bowel movements did not require oral laxatives; additional preprogrammed parameters achieved erections for intercourse. INTERPRETATION: Early SNM implantation in SCI patients may revolutionize neurogenic lower urinary tract (LUT) dysfunction management; it prevented detrusor overactivity and urinary incontinence, ensured normal bladder capacity, reduced UTI rates, and improved bowel and erectile functionality without nerve damage. CONCLUSION: Future SCI investigations will be conducted to evaluate the potential benefits of even earlier SNM placement to progressively enhance pelvic organ functionality. This new approach may provide important clues required for assessing whether neuronal information is passed through the sympathetic trunk ganglion to the brain after complete SCI. Further investigations are needed to determine if functional magnetic resonance imaging (fMRI) might be helpful for analyzing changes in brain function in patients with SNMs and those taking antimuscarinics.

Long-term biochemical evaluation of the androgen receptor pathway in males with disorders of sex development.

PURPOSE: Disorders of sex (DSD) development represent a serious condition. Most of the underlying mechanisms remain unclear. Disturbances within the androgen receptor (AR) pathway frequently account for 46 XY-DSDs. The individual gender-related outcome often is unsatisfactory. We present a long-term AR gene-mutation-associated follow-up in a group of 46 XY-DSD patients. METHODS: Twenty patients (46 XY) who underwent genitoplasty in infancy or early childhood were retrospectively identified. Median follow-up after surgery was 16 years. All were undervirilized at initial presentation. Thirteen had female gender assignment, and 7 were raised as males. A genital skin biopsy and subsequent fibroblast cultures were done. The specific binding of dihydrotestosterone, the thermostability of the receptor hormone complex, and 5-α-reductase activity were measured. AR gene mutations were detected by direct sequencing. The individual outcome was correlated with specific AR mutations. RESULTS: AR point mutations were detected in 12, 7 were previously unknown. There was no specific androgen binding in 3, reduced affinity in 9, and normal binding in 8 patients. 5-α-Reductase activity was normal in 15, reduced in 4 and completely absent in 1 patient. CONCLUSIONS: Retrospective evaluation revealed previously unknown and established AR gene mutations being associated with a distinct long-term outcome. Identification of the molecular mechanisms causing DSD will likely improve timely diagnosis and therapy. Exact characterization of AR activation and function may offer a treatment modality in affected patients. These data may allow us to give prognostic estimations on the individual outcome adding objective criteria for gender assignment in 46 XY-DSD patients.

[Immuno-oncological therapeutic options in high-risk non-muscle invasive bladder cancer]. / Immunonkologische Therapieoptionen des nicht-muskelinvasiven Urothelkarzinoms.

High-risk nonmuscle invasive bladder cancer (HR NMIBC) is an immunological malignancy. The standard therapy for HR NMIBC is based on transurethral bladder tumor resection with adjuvant Bacillus Calmette Guérin (BCG) instillation therapy. To prevent progression in case of BCG-refractory disease, early radical cystectomy is considered the therapy of choice according to the German S3 guidelines. With the advent of checkpoint inhibitors for the treatment of metastatic urological malignancies, a novel option for bladder preservation has been introduced for the treatment of HR NMIBC. The currently available data do not allow a meaningful conclusion on the long-term efficacy of PD-(L)1 (programmed cell death [ligand] 1) inhibitors due to the relatively short duration of oncological follow-up. Yet, it can be expected that checkpoint inhibitors will change the treatment algorithm of HR NMIBC in the next few years. Promising studies have been initiated to test the combination of local and systemic immunomodulation in terms of response and toxicity.

[Molecular tumor board-urothelial cancer]. / Molekulares Tumorboard ­ Urothelkarzinom.

BACKGROUND: Molecular tumor boards (MTB) are becoming more common. There are several molecular alterations in urothelial cancer a molecular tumor board can potentially rely on. OBJECTIVES: The aim is to specify molecular alterations and their correlations with different clinical endpoints and to highlight potential questions addressed to a MTB for urothelial cancer. MATERIALS AND METHODS: Descriptive review of the literature based on PubMed. RESULTS: The landscape of molecular alterations in urothelial cancer is heterogeneous. Thus, recent biomarker research has been focusing on biomarker panels and classifiers instead of single biomarkers. Recently, molecular subtypes of urothelial cancer have been identified and correlated with different clinical endpoints. Furthermore, circulating tumor cells and tumor DNA are under investigation as potential biomarkers. In addition to treatment response and prognosis, molecular markers are also needed to improve clinical staging prior to radical cystectomy or for proper patient selection for neoadjuvant chemotherapy. Erdafitinib is the first targeted therapy (fibroblast growth factor receptor [FGFR] alteration) in urothelial cancer that was recently approved (in the USA). CONCLUSIONS: Due to the lack of external validation, none of the identified biomarkers is currently established in clinical routine. In addition, there is no single driver mutation in urothelial cancer that facilitates the development of biomarkers and targeted therapies.

[Cost-effectiveness analysis of blue light cystoscopy with hexylaminolevulinate in transurethral resection of the bladder]. / Kosten-Effektivitäts-Analyse zur Verwendung der Blaulichtzystoskopie mit Hexylaminolevulinat bei der transurethralen Resektion der Harnblase.

BACKGROUND: Photodynamic diagnosis using the optical imaging agent hexaminolevulinate (HAL, Hexvix®, Ipsen Pharma GmbH, Ettlingen, Germany) as an adjunct to white light cystoscopy (WLC) during the initial transurethral resection of bladder tumours (TURB) improves the detection rate of bladder cancer and leads to fewer recurrences. OBJECTIVES: A cost-effectiveness analysis was carried out in order to calculate the consequences for the German healthcare system. METHODS: We combined a short-term decision tree and a Markov model to evaluate outcomes over a long period of time. The alternatives investigated were HAL-assisted blue light cystoscopy (BLC) as adjunct to WLC (HAL + BLC/WLC) compared with WLC alone in patients undergoing TURB. RESULTS: HAL + BLC/WLC compared to WLC alone was associated with 0.07 incremental quality-adjusted life years (QALYs) and cost savings of 537 € per patient. CONCLUSION: HAL + BLC/WLC compared with WLC alone resulted in both cost savings and improved patient outcome rendering it the "dominant" strategy.

[Non-muscle-invasive high-grade bladder cancer]. / Das nicht-muskelinvasive High-grade-Harnblasenkarzinom.

BACKGROUND: Non-muscle-invasive bladder cancer with a low-grade differentiation represents a special challenge. METHOD: Although urine cytology is still the most reliable and effective urine-based marker and there are no substantial novel aspects in this field, photodynamic diagnostics have the most important value in transurethral resection of the bladder (TURB) of high-grade T1 tumors and new techniques, such as hybrid knife TURB are coming up. The histopathological assessment of T1 tumors can be supplemented by a description of the exact penetration depth, so-called substaging and the invasion pattern. RESULTS: Intravesicle therapy with Bacillus Calmette-Guèrin (BCG) represents the gold standard and a pillar of bladder-preserving therapy and should be planned as maintenance therapy for at least 1 year. With the right risk constellation cystectomy is a safe and proven concept for high-grade bladder cancer, even without proof of muscle invasion.

[Laparoscopic partial nephrectomy for renal tumors. Time for a new standard?]. / Laparoskopische Nierenteilresektion bei Nierentumoren. Zeit für einen neuen Standard?

PURPOSE: Our aim was to evaluate the laparoscopic partial nephrectomies (LPN) performed at our hospital and compare the results with those from other current studies on partial nephrectomy. PATIENTS AND METHODS: Between March 2006 and January 2014, 280 patients were treated with LPN in our hospital. We evaluated age, sex, and surgical parameters like operating time, warm ischemia time (WIT), hospital stay, complications, tumor staging, grading, and size RESULTS: The patients were 61.6±12.4 years old. The median operating time for LPN was 134±51 min. A total of 30% of the operations were treated using the zero ischemia technique. The WIT was 19.9±9.8 min. The WIT of the last 50 LPN performed was 13±7 min. Complications were documented in 15% of the LPNs. CONCLUSION: LPN is a curative treatment option for the renal cell carcinoma similar to open partial nephrectomy; however, laparoscopy is associated with lower morbidity.

[Treatment of invasive bladder cancer: robot-assisted radical cystectomy and intracorporeal urinary diversion]. / Therapie des invasiven Harnblasenkarzinoms : Roboterassistierte radikale Zystektomie und intrakorporale Harnableitung.

PURPOSE: Robot-assisted radical cystectomy (RARC) and intracorporeal urinary diversion are only performed in a few centers of excellence worldwide. Functional and oncologic outcomes are comparable. We report on our experience with RARC and intracorporeal diversion. PATIENTS AND METHODS: We retrospectively identified 86 RARCs in 72 men and 14 women (mean age 69.7 years). All patients underwent robot-assisted radical cystectomy and pelvic lymphadenectomy followed by intracorporeal urinary diversion using ileal conduit or neobladder. Of the 86 patients, 24 patients (28%) underwent intracorporeal ileal conduit and 62 patients (72%) underwent intracorporeal neobladder formation. A Studer pouch was created in all who underwent intracorporeal neobladder diversion. Cancer specific survival (CSS) and overall survival (OS) are reported. RESULTS: The mean operative time was 418.9 min (range 205-690 min) and blood loss was 380 ml (range 100-1000 ml). The mean hospital stay was 17.5 days (range 5-62 days). All the surgeries were completed with no open conversions. Minor complications (grade I and II) were reported in 23 patients, while major complications (grade III and above) were reported in 21 patients. The mean nodal yield was 20.3 (range 0-46). Positive margins were found in in 8%. The average follow-up was 31.5 months (range 3-52 months). Continence could be achieved in 88% of patients who received an intracorporeal neobladder. The cancer-specific survival (CSS) and overall survival (OS) were 80% and 70%, respectively. CONCLUSION: RARC with intracorporeal diversion seems to be safe and reproducible in tertiary centers with robotic expertise. Operative times are acceptable and complications as well as functional and oncologic outcomes are comparable. Further standardization of RARC with intracorporeal diversion may lead to a wider adoption of the approach.

[Complex residual tumors after chemotherapy of nonseminomatous germ cell tumors. Laparoscopic management - limits and chances]. / Komplexe Residualtumoren nach Chemotherapie bei nichtseminomatösen Keimzelltumoren. Laparoskopisches Management - Grenzen und Chancen.

PURPOSE: Laparoscopic retroperitoneal lymph node dissection (L-RPLND) is often required in patients with metastatic nonseminomatous germ cell tumors (NSGCT) and residual tumors after chemotherapy. Laparoscopy has become established as a safe procedure in the surgical management of these tumors. Due to the rapid development of laparoscopy, complex retroperitoneal and even intrathoracic residuals can also be treated in high volume centers. PATIENTS AND METHODS: This study included 21 retrospectively identified NSGCT and seminoma patients (mean age 29 years) with metastatic disease and clinical stage (CS) IIA-IIIB. A bilateral L-RPLND was performed in all male patients between 2009 and 2014. In 19 patients an infiltration of the great vessels was detected during surgery and vascular reconstruction was necessary. In 2 patients an intrathoracic residual 5.4 cm and 7 cm in size, respectively, was diagnosed during follow-up. Exclusion criteria for L-RPLND were positive tumor markers after chemotherapy, patients with local recurrence after previous open L-RPLND and patients with excessive vascular involvement. RESULTS: In this series no conversions to open surgery were necessary. The mean tumor size post-chemotherapy was 3.6 cm (range 1.5-9.7 cm). The mean measured blood loss was 294 ml (range 50-1000 ml). The mean hospitalization time was 6 days (range 3-9 days) and mean follow-up was 16 months (range 1-37 months). No complications higher than grade II (Clavien-Dindo classification) were registered in the immediate postoperative course. During the follow-up period no in-field recurrences were registered. CONCLUSION: The L-RPLND seems to be a safe alternative surgical procedure for certain complex residuals with vascular involvement after chemotherapy of testicular cancer. Bilateral L-RPLND is technically feasible and reproducible under guaranteed oncological principles. An infiltration of the great vessels and also intrathoracic residuals can be managed in selected patients without compromising the clinical and oncological course.

[Transurethral resection of bladder tumors: management of complications]. / Transurethrale Resektion der Harnblase: Komplikationsmanagement.

As a frequent endourological procedure, transurethral resection of bladder tumors (TURB) represents a major field of activity for urological surgeons. Although TURB represents an endoscopic training procedure for urology residents, there are clear requirements for the quality of the surgical procedure as such. The knowledge of possible complications and their management are essential for urologists active in the clinical field. Bleeding complications, bladder perforation, infections and injuries to the ureteral orifice are the most frequently observed complications. This article summarizes the essential risks and complications as well as the corresponding preventive and therapeutic measures.

[Elective organ and function preservation in ureter and renal pelvis tumors]. / Elektiver Organ- und Funktionserhalt beim Harnleiter- und Nierenbeckentumor.

With the technical innovations of smaller, flexible ureteroscopes, color-filtered imaging, and endoscopic laser technology, organ-preserving treatment for upper urinary tract transitional cell carcinoma has become feasible. While in the past, radical nephroureterectomy was the sole gold standard approach for the treatment of upper urinary tract tumors, the endoscopic approach is no longer restricted to only patients with the imperative indication of kidney preservation. Initial clinical results have demonstrated oncologic efficacy of endoscopic management or segmental ureteral resection. However, careful preoperative risk-assessment and close endoscopic follow-up are mandatory.