First Comparison of Retroperitoneal Versus Transperitoneal Robot-Assisted Nephroureterectomy with Bladder Cuff: A Single Center Study.

INTRODUCTION: After recent presentation of the first complete robot-assisted retroperitoneal nephroureterectomy with bladder cuff (RRNU) for patients with upper tract urothelial cancer (UTUC), we aimed to compare this new surgical technique with robot-assisted transperitoneal nephroureterectomy (TRNU) representing the current standard of care. METHODS: Robot-assisted nephroureterectomies (NUs) were retrospectively analyzed and compared based on two groups: transperitoneal versus retroperitoneal approach. Baseline data were collected for patient demographics, tumor characteristics, intra- (EAUiaiC) and postoperative (Clavien-Dindo) complications, and perioperative variables. Tumor characteristics included grade of malignancy, clinical stage, and surgical margin status. Short-term follow-up data including 30-day readmission rates were collected. Statistical analyses were performed assuming a significant p-value of < 0.05. RESULTS: The analysis includes perioperative patient data after proven UTUC of 24 TRNU versus 12 RRNU (mean age: 70 versus 71 years; BMI: 25.9 versus 26.1 kg/m2; CCI score ≥ 4: 83% versus 75%; ASA score ≥ 3: 37% vs 33%). Intraoperative (16.4% vs 0%, p = 0.35) and postoperative (25% vs 12.5%, p = 0.64) complications demonstrated no significant discrepancy. Notably, RRNU demonstrated significantly shorter surgery time (p < 0.05) and length of stay (p < 0.05). There was no significant difference in histopathological tumor characteristics, whereas significantly more lymph nodes were removed through RRNU (11.0±3.3 vs. 6.4±5.1, p < 0.05). Finally, no statistical difference was shown in short-term follow-up. CONCLUSION: We report the first head-to-head comparison between RRNU and TRNU. RRNU proves to be a safe and feasible approach which appears to be non-inferior to TRNU. RRNU expands the spectrum of minimally invasive treatment options, particularly for patients with major previous abdominal surgery.

First completely robot-assisted retroperitoneal nephroureterectomy with bladder cuff: a step-by-step technique.

INTRODUCTION: While various surgical techniques have been reported for open and minimally invasive treatment of upper tract urothelial cancer (UTUC), the procedure of robot-assisted nephroureterectomy (NU) with bladder cuff has never been reported using only retroperitoneum without entering abdominal cavity. We developed a novel port placement and technique allowing to perform robot-assisted NU by a unique retroperitoneal approach. METHODS: Between February and June 2021 patients with history of UTUC were treated by robot-assisted NU completely restricted to retroperitoneal space using a singular trocar placement and a two-step docking without relocation of the surgical robot. Patient characteristics, perioperative outcomes and short-term follow-up were prospectively analyzed. RESULTS: The analysis included five patients [median age: 73 years; BMI: 27.2 kg/m2; Charlson comorbidity index 5]. All five patients had UTUC with a mean tumor size of 3.02 cm (range 0.9-6.0). UTUC was localized to distal ureter in two and to kidney in three cases. No positive surgical margins were noted for all patients with UTUC [1 low-grade and 4 high-grade]. Retroperitoneal lymphadenectomy in three patients did not reveal positive nodes. No intraoperative adverse events exceeding EAUiaiC classification ≥ 2 were observed, while median EBL was 150 ml (IQR 100-250). No patient experienced postoperative complications exceeding Clavien-Dindo classification ≥ 3a. Median hospital stay was 5.4d without any 30-d readmission. CONCLUSION: We demonstrate safety and feasibility of the first entire robot-assisted retroperitoneal nephroureterectomy (RRNU) with bladder cuff. This surgical technique is easily reproducible, while surgical outcomes are similar to other established techniques.

Robot-assisted simple prostatectomy versus open simple prostatectomy: a single-center comparison.

PURPOSE: Open simple prostatectomy (OSP) is a standard surgical technique for patients with benign prostatic hyperplasia with prostate size larger than 80 ml. As a minimally invasive approach, robot-assisted simple prostatectomy (RASP) emerged as a feasible surgical alternative. Currently, there are no definite recommendations for the standard use of RASP. Therefore, we aimed at investigating various clinical outcomes comparing RASP with OSP. METHODS: In this retrospective single-center study, we evaluated clinical data from 103 RASP and 31 OSP patients. Both cohorts were compared regarding different clinical characteristics with and without propensity score matching. To detect independent predictive factors for clinical outcomes, multivariate logistic regression analysis was performed. RESULTS: Robot-assisted simple prostatectomy patients demonstrated a lower estimated blood loss and need for postoperative blood transfusions as well as less postoperative complications. OSP had a shorter operative time (125 min vs. 182 min) longer hospital stay (11 days vs. 9 days) and longer time to catheter removal (8 days vs. 6 days). In the multivariate analysis, RASP was identified as an independent predictor for longer operative time, lower estimated blood loss, shorter length of hospital stay, shorter time to catheter removal, less postoperative complications and blood transfusions. CONCLUSION: Robot-assisted simple prostatectomy is a safe alternative to OSP with less perioperative and postoperative morbidity. Whether OSP (shorter operative time) or RASP (shorter length of hospital stay) has a more favorable economic impact depends on the particular conditions of different health care systems. Further prospective comparative research is warranted to define the value of RASP in the current surgical management of benign prostatic hyperplasia.

OLEOGEL-S10 TO ACCELERATE HEALING OF DONOR SITES: MONOCENTRIC RESULTS OF PHASE III CLINICAL TRIAL.

MATERIAL AND METHODS: Oleogel-S10, an ointment containing betulin-rich triterpene dry extract from birch bark was tested in an open, blindly evaluated, prospective, controlled, randomized multicentre study to improve wound healing in donor sites. The primary endpoint was time to wound closure, and secondary endpoints were scar related measurements at the time of wound closure, and 3 and 12 months after wound closure (POSAS, laser speckle contrast analysis, viscoelastic analysis). RESULTS: We report the results from a single centre (Department of Burns and Reconstructive Surgery, University Hospital Brno) of this phase III clinical trial. A total of 32 patients (25 men and 7 women) were included with the mean patient age of 41.8 years (SD, ±11.66). The mean extent of patients donor sites in the study was 56.77cm2 (SD, ±20.39). Median healing time of the verum group (Oleogel-S10) was 7 days (95% Confidence Interval 7-8 days) and for controls 8 days (95% CI 7-10 days). Comparison of POSAS data from the verum group revealed significantly lower values at all three time points as compared to the controls. Perfusion of scars of the verum group reached on average of 115 perfusion units at the end of treatment; the average was 69.8 perfusion units at the 3-month follow-up and 50.2 perfusion units at the 12-month follow-up. Control sites displayed significantly higher values at all time points (122.2 perfusion units, 73.9 perfusion units, 52.2 perfusion units). Significant differences were detected in the skins viscoelastic properties, with sites treated with Oleogel-S10 displaying more favourable values. CONCLUSION: In our results, we demonstrate the significant effectiveness of Oleogel-S10 in donor sites healingKeywords: Donor site, Triterpenes, Oleogel-S10, wound closure.

The hydrodynamic basis of the vacuum cleaner effect in continuous-flow PCNL instruments: an empiric approach and mathematical model.

PURPOSE: Passive removal of stone fragments in the irrigation stream is one of the characteristics in continuous-flow PCNL instruments. So far the physical principle of this so-called vacuum cleaner effect has not been fully understood yet. The aim of the study was to empirically prove the existence of the vacuum cleaner effect and to develop a physical hypothesis and generate a mathematical model for this phenomenon. METHODS: In an empiric approach, common low-pressure PCNL instruments and conventional PCNL sheaths were tested using an in vitro model. Flow characteristics were visualized by coloring of irrigation fluid. Influence of irrigation pressure, sheath diameter, sheath design, nephroscope design and position of the nephroscope was assessed. Experiments were digitally recorded for further slow-motion analysis to deduce a physical model. RESULTS: In each tested nephroscope design, we could observe the vacuum cleaner effect. Increase in irrigation pressure and reduction in cross section of sheath sustained the effect. Slow-motion analysis of colored flow revealed a synergism of two effects causing suction and transportation of the stone. For the first time, our model showed a flow reversal in the sheath as an integral part of the origin of the stone transportation during vacuum cleaner effect. The application of Bernoulli's equation provided the explanation of these effects and confirmed our experimental results. CONCLUSIONS: We widen the understanding of PCNL with a conclusive physical model, which explains fluid mechanics of the vacuum cleaner effect.

Impact of primary resistance to front-line targeted therapy in metastatic renal cell carcinoma on subsequent immune-checkpoint-inhibition.

INTRODUCTION: Synergistic effects have been discussed for tyrosine kinase (TKI) and immune checkpoint inhibitors (ICI). Primary resistance to TKI might disturb subsequent ICI effectiveness. The objective was to investigate, if primary resistance to 1st line TKI monotherapy predicts response to ICI in subsequent therapy lines and impacts overall survival (OS) in advanced renal cell carcinoma (aRCC). MATERIALS AND METHODS: Retrospectively, aRCC patients which received front-line TKI from 2016 to 2019 were analyzed for the outcomes primary resistance (1LR), response to sequential ICI therapy, progression free survival (PFS) and overall survival (OS). Kaplan-Meier-estimates, Cox proportional hazards and logistic regression were used. RESULTS: Primary resistance to front-line TKI was observed in 27 (53%) of 51 patients. Groups with disease control (DC) and 1st line TKI resistance (1LR) were not different at baseline with regard to clinicopathological features. Median duration on 1st line therapy was significantly shorter in the 1LR (5.1 months) than in the DC (14.7 months) group (p = 0.01). Sequential therapy was started in 21 (75%) and 12 (52%) patients of 1LR and DC groups using nivolumab in 16 (76%) vs. 11 (92%) cases (p > 0.05). Logistic regression revealed that 1LR status, neutrophil-to-lymphocyte ratio < 3, IMDC favorable prognosis and clear cell histology had no significant impact on responsiveness to ICI in subsequent therapy lines. Cox proportional hazards demonstrated no significant association of 1LR status with PFS and OS in patients who received subsequent ICI treatment. CONCLUSION: Primary TKI resistance of aRCC was neither significantly associated with responsiveness to ICI during sequential therapy nor with PFS and OS. This adds the evidence for ICI based sequential therapy in primary TKI resistant aRCC.

[Report template from the German Society of Urology and the German Radiological Society for standardized, structured reporting of native computed tomography scans in the diagnosis of urinary stones]. / Befundvorlage der Deutschen Gesellschaft für Urologie e. V. und der Deutschen Röntgengesellschaft zur standardisierten strukturierten Befundung von nativen Computertomographien in der Harnsteindiagnostik.

Standardized structured radiological reporting (SSRB) has been promoted in recent years. The aims of SSRB include that reports be complete, clear, understandable, and stringent. Repetitions or superfluous content should be avoided. In addition, there are advantages in the presentation of chronological sequences, tracking and correlations with structured findings from other disciplines and also the use of artificial intelligence (AI)-based methods. The development of the presented template for SSRB of native computed tomography for urinary stones followed the "process for the creation of quality-assured and consensus-based report templates as well as subsequent continuous quality control and updating" proposed by the German Radiological Society (DRG). This includes several stages of drafts, consensus meetings and further developments. The final version was published on the DRG website ( www.befundung.drg.de ). The template will be checked annually by the steering group and adjusted as necessary. The template contains 6 organ domains (e.g., right kidney) for which entries can be made for a total of 21 different items, mostly with selection windows. If "no evidence of stones" is selected for an organ in the first query, the query automatically jumps to the next organ, so that the processing can be processed very quickly despite the potentially high total number of individual queries for all organs. The German, European, and North American Radiological Societies perceive the establishment of a standardized structured diagnosis of tomographic imaging methods not only in oncological radiology as one of the current central tasks. With the present template for the description of computed tomographic findings for urinary stone diagnostics, we are presenting the first version of a urological template. Further templates for urological diseases are to follow.

Assessment of a novel smartglass-based point-of-care fusion approach for mixed reality-assisted targeted prostate biopsy: A pilot proof-of-concept study.

Purpose: While several biopsy techniques and platforms for magnetic resonance imaging (MRI)-guided targeted biopsy of the prostate have been established, none of them has proven definite superiority. Augmented and virtual reality (mixed reality) smartglasses have emerged as an innovative technology to support image-guidance and optimize accuracy during medical interventions. We aimed to investigate the benefits of smartglasses for MRI-guided mixed reality-assisted cognitive targeted biopsy of the prostate. Methods: For prospectively collected patients with suspect prostate PIRADS lesions, multiparametric MRI was uploaded to a smartglass (Microsoft® Hololens I), and smartglass-assisted targeted biopsy (SMART TB) of the prostate was executed by generation of a cognitive fusion technology at the point-of-care. Detection rates of prostate cancer (PCA) were compared between SMART TB and 12-core systematic biopsy. Assessment of SMART-TB was executed by the two performing surgeons based on 10 domains on a 10-point scale ranging from bad (1) to excellent (10). Results: SMART TB and systematic biopsy of the prostate were performed for 10 patients with a total of 17 suspect PIRADS lesions (PIRADS 3, n = 6; PIRADS 4, n = 6; PIRADS 5, n = 5). PCA detection rate per core was significant (p < 0.05) higher for SMART TB (47%) than for systematic biopsy (19%). Likelihood for PCA according to each core of a PIRADS lesion (17%, PIRADS 3; 58%, PIRADS 4; 67%, PIRADS 5) demonstrated convenient accuracy. Feasibility scores for SMART TB were high for practicality (10), multitasking (10), execution speed (9), comfort (8), improvement of surgery (8) and image quality (8), medium for physical stress (6) and device handling (6) and low for device weight (5) and battery autonomy (4). Conclusion: SMART TB has the potential to increase accuracy for PCA detection and might enhance cognitive MRI-guided targeted prostate biopsy in the future.

Monitoring of the responsiveness to noxious stimuli during anaesthesia with propofol and remifentanil by using RIII reflex threshold and bispectral index.

BACKGROUND: Movement responses are an important indicator of noxious perception in the unconscious state. To allow for a continual monitoring of the responsiveness to noxious stimuli during general anaesthesia, surrogate parameters are needed. Here we compare the performance of the bispectral index (BIS) and the RIII threshold in predicting reactions to noxious stimuli during anaesthesia with propofol and remifentanil. METHODS: Twenty male volunteers were included. The first 10 subjects received constant concentrations of propofol while remifentanil concentrations were increased stepwise. The other 10 subjects each received high propofol concentrations combined with different low remifentanil concentrations and also low propofol concentrations combined with different high remifentanil concentrations. In all subjects, the reactions to an 80 mA 30 s tetanic stimulus were tested every 5 min. BIS and RIII threshold were recorded continually in all subjects. RESULTS: Nineteen subjects completed the study. The population prediction probability for reactions to the noxious stimuli amounted to 0.86 for the BIS and to 0.84 for the RIII threshold in the first 10 subjects (P>0.05, PKDMACRO). In the other nine subjects, the prediction probabilities amounted to 0.64 for the BIS and to 0.77 for the RIII threshold (P<0.05, PKDMACRO). All population prediction probability values differed significantly from 0.5 (P<0.01, PKDMACRO). CONCLUSIONS: RIII threshold and BIS are both influenced dose-dependently by remifentanil at those concentrations that suppress reactions to noxious stimuli. The susceptibility of the parameters to remifentanil concentration seems to be of a similar quality. Under different ratios of propofol and remifentanil concentrations, the RIII threshold correlates with non-responsiveness better than the BIS.

Unsuccessful therapy of combined mycotic infection in a severely burned patient: a case study.

Patients with burn trauma are always in danger of contracting an infection. Although invasive mycotic infections are not as frequent as bacterial infections, high mortality and in many cases difficult diagnostics pose a serious threat not only for neutropenic patients. In more extensive burns the status is further complicated by specifically compromised immunity. The most frequent species of micromycetes isolated in burn patients are Candida spp. and Aspergillus spp. Zygomycetes represents a relatively uncommon isolation worldwide (up to 2% of all fungi. We present a case study of a young patient with 82% TBSA (total body surface area) burns, where we isolated simultaneously 3 different types of micromycetes (Aspergillus fumigatus, Fusarium sp., Absidia sp.). Mycotic infection is understood primarily as a complication in neutropenic patients and, after prophylactic antibiotic and antimycotic administration, in extensive burn trauma patients. The case ended with the death of the patient due to severe sepsis caused by the multiresistant strain Pseudomonas aeruginosa.

[Current concepts on the pathogenesis of urinary stones]. / Aktuelle Konzepte zur Pathogenese von Harnsteinen.

The process of kidney stone formation is complex and still not completely understood. Supersaturation and crystallization are the main drivers for the etiopathogenesis of uric acid, xanthine and cystine stones but this physicochemical concept fails to adequately explain the formation of calcium-based nephrolithiasis, which represents the majority of kidney stones. Contemporary concepts of the pathogenesis of calcium-based nephrolithiasis focus on a nidus-associated stone formation of calcium-based nephrolithiasis on Randall's plaques or on plugs of Bellini's duct. Randall's plaques originate from the interaction of interstitial calcium supersaturation in the renal papilla, vascular and interstitial inflammatory processes and mineral deposits of calcifying nanoparticles on the basal membrane of the thin ascending branch of the loop of Henle; however, plugs of Bellini's duct are assumed to be caused by mineral deposits on the wall of the collecting ducts. Aggregation and overgrowth are influenced by the interaction of matrix proteins with calcium supersaturated urine, by an imbalance between promoters and inhibitors of stone formation in the calyceal urine. Current research has elucidated many factors contributing to stone formation by revealing novel insights into the physiology of nephron and papilla, by analyzing vascular, inflammatory and calcifying processes in the renal medulla, by examining the proteome, the microbiome, promoters and inhibitors of stone formation in the urine and by conducting the first genome-wide association studies; however, more future research is mandatory to fill the gap of knowledge and hopefully, to obtain novel prophylactic, therapeutic and metaphylactic tools beyond the current state of knowledge.

Nitric oxide controls oscillatory activity in thalamocortical neurons.

Nitric oxide (NO) is considered a diffusible messenger involved in neuronal communication, although the post-synaptic target cells of NO action and the associated biological function in the CNS are still a matter of controversy. Within the discrete pattern of NO-synthesizing neurons in the brain, NO synthase is specifically colocalized with the cholinergic brain stem-thalamic system, which is thought to regulate the state-dependent activity of the thalamocortical circuit. Here we report evidence indicating that the release of NO onto thalamocortical neurons results in an alteration in voltage dependence of the hyperpolarization-activated cation conductance, probably mediated via the cGMP system. NO selectively dampens oscillatory neuronal activity, indicating a rapidly diffusing signaling mechanism that controls the functional state of the thalamocortical network.

[Watchful waiting and active surveillance of small renal masses]. / "Watchful waiting" und aktive Überwachung kleiner Nierentumoren.

The incidence of small renal masses ≤4 cm is increasing due to the widespread use of cross-sectional imaging. The majority of these represent indolent forms, but the risk for developing metastases is reported in up to 6% of patients. Particularly in old and comorbid patients surgery might be harmful overtreatment. Thus, there is an increasing demand to establish oncologically safe active surveillance protocols. Radiographic or biopsy-based biological markers to appropriately designate candidates for active surveillance are currently the focus of research.

[Standard surgery for small renal masses (<4 cm)]. / Standardoperationen bei kleinen Nierentumoren (<4 cm).

BACKGROUND: Several new treatment strategies have emerged in the treatment of small renal masses (<4 cm in diameter). Active surveillance and ablative techniques have been introduced but it remains unclear which patients will benefit the most from these new treatment options. A surgical approach remains standard of care. In recent decades, radical nephrectomy has been replaced by nephron-sparing surgery for the management of small renal masses. RESULTS: In addition to the open partial nephrectomy, which is considered the standard approach, the number of surgeries performed using minimally invasive techniques is increasing. Recent data show that there might be some benefits such as less blood loss. The disadvantages shown by laparoscopic partial nephrectomy such as prolonged warm ischemia, longer operation times, and postoperative renal impairment might be negligible for the robotic approach. Therefore, current guidelines allow these approaches in addition to open partial nephrectomy if sufficient surgical expertise is given.

Clinical outcomes and costs of reusable and single-use flexible ureterorenoscopes: a prospective cohort study.

The purpose of this study is to analyze clinical outcomes and costs of single-use flexible ureterorenoscopes in comparison with reusable flexible ureterorenoscopes in a tertiary referral center. Prospectively, 68 flexible ureterorenoscopies utilizing reusable (Flex-X2S, Flex-XC, Karl Storz) and 68 applying single-use flexible ureterorenoscopes (LithoVue, Boston Scientific) were collected. Clinical outcome parameters such as overall success rate, complication rates according to Clavien-Dindo, operation time and radiation exposure time were measured. Cost analysis was based on purchase costs and recurrent costs for repair and reprocessing divided by number of procedures. In each group 68 procedures were available for evaluation. In 91% of reusable and 88% of single-use ureterorenoscopies stone disease was treated with a mean stone burden of 101 ± 226 and 90 ± 244 mm2 and lower pole involvement in 47 and 41%, respectively (p > 0.05). Comparing clinical outcomes of reusable vs. single-use instruments revealed no significant difference for overall success rates (81 vs. 87%), stone-free rates (82 vs. 85%), operation time (76.2 ± 46.8 vs. 76.8 ± 40.2 min), radiation exposure time (3.83 ± 3.15 vs. 3.93 ± 4.43 min) and complication rates (7 vs. 17%) (p > 0.05). A wide range of repair and purchase costs resulted in total to $1212-$1743 per procedure for reusable ureterorenoscopy whereas price of single-use ureterorenoscopy was $1300-$3180 per procedure. The current work provided evidence for equal clinical effectiveness of reusable and single-use flexible ureterorenoscopes. Partially overlapping ranges of costs for single-use and reusable scopes stress the importance to precisely know the expenses and caseload when negotiating purchase prices, repair prices and warranty conditions.

From novice to expert: analyzing the learning curve for MRI-transrectal ultrasonography fusion-guided transrectal prostate biopsy.

PURPOSE: To investigate the learning curve of a novice in MRI/TRUS software fusion biopsy and to compare his results with the expert standard at our institution. METHODS: Overall 126 MRI/TRUS fusion-guided transrectal biopsies were performed using an electromagnetic tracking ultrasonography platform. The learning progress of the novice was evaluated comparing his initial 42 procedures (group A) with his following 42 (group B). The institution's expert standard (group C), which was compared to the novice's groups, was defined by the expert's experience of 42 MRI/TRUS fusion biopsies. Primary learning curve parameters were targeted biopsy detection quotient and biopsy time. RESULTS: Overall detection of prostate cancer was 64% (27/42), 62% (26/42) and 62% (26/42) in groups A, B and C, respectively. The median target biopsy detection quotient significantly increased (p = 0.04) in group B (0.75, interquartile range (IQR) 0.25-1.0) compared to group A. (0.33, IQR 0.2-0.5). Group C revealed a median detection quotient of 0.5 (IQR 0.25-0.76) that did not differ significantly from the novice's groups (p = 0.2). Median biopsy time was significantly higher in group A (45 min, IQR 33-50 min) compared to groups B (25 min, IQR 23-29 min) and C (24 min, IQR 16-46 min) (p < 0.01). CONCLUSIONS: The present study revealed the individual learning curve of a novice in MRI/TRUS fusion biopsy and demonstrated significant learning progress regarding targeted biopsy detection quotient and biopsy time.

TuBaFrost 3: regulatory and ethical issues on the exchange of residual tissue for research across Europe.

The regulatory regimes for research with residual tissue and accompanying data differ widely between countries in the European Union (EU): from specific consent to opt-out or even no consent at all. This could greatly hamper research where the exchange of tissue and accompanying data has become the gold standard, like in TubaFrost. Instead of adhering to international guidelines, which have a democratic deficit, or an attempt for a new set of possible harmonising rules, TubaFrost chose to create a coordinating rule: if tissue may legitimately be used for a certain kind of research in the country where it was taken and under whose jurisdiction the patient falls, it may also be used for such research in the country where it is sent to in the context of a scientific program even if in that other country other regulations would apply for research with residual tissue taken from patients under their jurisdiction. This coordinating rule has a sound basis in EU law in general and will solve the problems related to diverging national regulatory regimes in the case of cross national research with residual tissue.