Ulrich Wetterauer

CALCITONIN GENE-RELATED PEPTIDE: POSSIBLY NEUROTRANSMITTER CONTRIBUTES TO PENILE ERECTION IN MONKEYS

The distribution of calcitonin gene-related peptide (CGRP) immunoreactivity in the cavernous tissue and the erectile response to intracavernous injection of CGRP was investigated in 7 monkeys. Intracavernous CGRP increased cavernous arterial flow and induced cavernous smooth muscle relaxation and venous outflow occlusion. Intracavernous injection of CGRP antibody did not significantly change the erectile response to cavernous nerve stimulation. Histologic staining for CGRP immunoreactivity showed nerve fiber-like staining within the cavernous arterial wall and the cavernous smooth muscles. These data suggest that CGRP may contribute to penile erection in monkeys.

Retrograde Intrarenal Surgery in Treatment of Nephrolithiasis: Is a 100% Stone-Free Rate Achievable?

PURPOSEnTo achieve an almost 100% stone-free rate by means of further developing and standardizing the procedure.nnnPATIENTS AND METHODSn100 consecutive patients with single or multiple renal calculi were prospectively enrolled in the study. Flexible ureterorenoscopy was performed as a completely standardized operation by the same two experienced surgeons. Primary outcome was an endoscopic (immediate) stone-free status as determined by endoscopic inspection at the end of surgery. In cases of residual fragments, a reevaluation by CT was performed after 3 months.nnnRESULTSnThe endoscopic stone-free rate was 97%. In three patients with a cumulative stone size >20 mm, a completely stone-free status could not be achieved in the primary procedure. In these patients, a CT scan after 3 months showed complete clearance from all residual fragments in two; this translates into a primary (after one procedure) stone-free rate after 3 months of 99%. Medium cumulative stone size was 9.8 mm (4-40 mm); in 44 patients, multiple calculi were extracted. Forty-nine patients received a ureteral stent at the end of the operation; two patients had to have stent placement for new onset hydronephrosis and/or colicky pain or fever. Overall complication rate was 7%. Results are limited, because no routine CT scan was used to evaluate stone clearance.nnnCONCLUSIONnBy means of a standardized surgical approach and use of technical equipment of the newest generation, it is possible to achieve very high stone-free rates without compromising safety. This approach, however, necessitates use of considerable resources, both technical/surgical and financial.

Erectile Responses to Intracavernous Papaverine and Phentolamine: Comparison of Single and Combined Delivery

In a prospective study of 15 consecutive impotent patients we evaluated the erectile responses to intracavernous injections of standardized doses of papaverine and phentolamine alone and in combination. Of the 15 patients 13 achieved a full erection with the drug combination, whereas only 6 achieved a full erection with papaverine and 1 with phentolamine. Our results suggest an effective alternative to the use of papaverine alone, whose long-term sequelae have been shown to be deleterious.

The Effect of Venous Incompetence and Arterial Insufficiency on Erectile Function: An Animal Model

We designed an animal model to elucidate the effect of venous leakage and arterial insufficiency on erectile function. In 10 dogs, electrodes were implanted around the cavernous nerves for electroerection and blood flow in the internal pudendal artery was recorded. Venous leakage was mimicked by inserting needles of varying gauges (30 to 16G) into the corpus cavernosum and the erectile response to neurostimulation was recorded before and after the creation of the leak. The relationship between the size and the amount of the venous leakage, the changes in the intracavernous pressure (peak and drop), and the changes in the peak and maintenance arterial blood flow were documented. Arterial blood flow was then reduced by 25 and 50 per cent by means of a screw clamp on the terminal aorta. The erectile response to neurostimulation was again determined, with the same electrical parameters, first with reduced blood flow alone, then in combination with leakage of varying size. Our results showed that minor cavernous vein leakage in the presence of normal arterial flow and a healthy sinusoidal system had a minimal effect on erectile function owing to a compensatory increase in penile blood flow. However, when reduction of arterial blood flow was superimposed on venous leakage, even of a minor degree, the erectile response to neurostimulation was markedly impaired.

Comparison of (68)Ga-HBED-CC PSMA-PET/CT and multiparametric MRI for gross tumour volume detection in patients with primary prostate cancer based on slice by slice comparison with histopathology.

Purpose: The exact detection and delineation of the intraprostatic tumour burden is crucial for treatment planning in primary prostate cancer (PCa). We compared 68Ga-HBED-CC-PSMA PET/CT with multiparametric MRI (mpMRI) for diagnosis and tumour delineation in patients with primary PCa based on slice by slice correlation with histopathological reference material. Methodology: Seven patients with histopathologically proven primary PCa underwent 68Ga-HBED-CC-PSMA PET/CT and MRI followed by radical prostatectomy. Resected prostates were scanned by ex-vivo CT in a special localizer and prepared for histopathology. Invasive PCa was delineated on a HE stained histologic tissue slide and matched to ex-vivo CT to obtain gross tumor volume (GTV-)histo. Ex-vivo CT including GTV-histo and MRI data were matched to in-vivo CT(PET). Consensus contours based on MRI (GTV-MRI), PSMA PET (GTV-PET) or the combination of both (GTV-union/-intersection) were created. In each in-vivo CT slice the prostate was separated into 4 equal segments and sensitivity and specificity for PSMA PET and mpMRI were assessed by comparison with histological reference material. Furthermore, the spatial overlap between GTV-histo and GTV-PET/-MRI and the Sørensen-Dice coefficient (DSC) were calculated. In the case of multifocal PCa (4/7 patients), SUV values (PSMA PET) and ADC-values (diffusion weighted MRI) were obtained for each lesion. Results: PSMA PET and mpMRI detected PCa in all patients. GTV-histo was detected in 225 of 340 segments (66.2%). Sensitivity and specificity for GTV-PET, GTV-MRI, GTV-union and GTV-intersection were 75% and 87%, 70% and 82%, 82% and 67%, 55% and 99%, respectively. GTV-histo had on average the highest overlap with GTV-union (57±22%), which was significantly higher than overlap with GTV-MRI (p=0.016) and GTV-PET (p=0.016), respectively. The mean DSC for GTV-union, GTV-PET and GTV-MRI was 0.51 (±0.18), 0.45 (±0.17) and 0.48 (±0.19), respectively. In every patient with multifocal PCa there was one lesion which had both the highest SUV and the lowest ADC-value (mean and max). Conclusion: In a slice by slice analysis with histopathology, 68Ga-HBED-CC-PSMA PET/CT and mpMRI showed high sensitivity and specificity in detection of primary PCa. A combination of both methods performed even better in terms of sensitivity (GTV-union) and specificity (GTV-intersection). A moderate to good spatial overlap with GTV-histo was observed for PSMA PET/CT and mpMRI alone which was significantly improved by GTV-union. Further studies are warranted to analyse the impact of these preliminary findings for diagnostic (multimodal guided TRUS biopsy) and therapeutic (focal therapy) strategies in primary PCa.

Diagnostic Accuracy of Ga-68-HBED-CC-PSMA-Ligand-PET/CT before Salvage Lymph Node Dissection for Recurrent Prostate Cancer

Background: By targeting the prostate-specific membrane antigen (PSMA) on prostate cancer (PCa) cells PSMA-PET/CT shows great potential in locating the site of biochemical recurrence even at low PSA (Prostate-specific antigen)-levels. Accurate imaging of PCa recurrent lymph node metastases (LNM) is crucial for metastases directed therapies such as salvage-lymph node dissection (salvage-LND). Objective: To evaluate the diagnostic accuracy of PSMA-PET/CT for detection of affected lymph-node regions at salvage-LND for nodal recurrence of PCa. Design, setting and participants: 30 patients with the suspicion of exclusively nodal PCa-relapse after primary therapy underwent a template pelvic and/or retroperitoneal salvage-LND after whole body 68-Ga-PSMA-PET/CT. The diagnostic accuracy of PET/CT was evaluated in comparison to the histopathology of 965 resected lymph nodes (LN) dissected from 68 main regions (pelvic left/right, retroperitoneal) and 289 subregions (common iliac, external iliac, obturator, internal iliac, presacral, aortic-bifurcation, aortal, caval). LNM and tumor deposits in LNM were measured bidimensionally in the histopathology. PSMA-expression was analyzed by immunohistochemistry in LNM. Results: LNM were present in 11.4% of the resected LN (110/965) resulting in 45 positive main regions and 85 positive subregions. PET/CT was true positive in 41 main regions and 69 subregions. Three PET-negative main regions and 16 PET-negative subregions finally contained LNM, the majority of these false negative subregions (13/16) were in neighboring regions of true-positive subregions. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy were: main region-based 93.2%, 100%, 100%, 88.9% and 95.6%, subregion-based 81.2%, 99.5%, 98.6%, 92.7 and 94.1%. Median short diameters of tumor deposits in LNM resected from false-negative subregions (1.3 mm) were significantly smaller than in LNM removed from true-positive subregions (5.5 mm, p<0.0001). Based on anatomical subregions containing just one LNM, the necessary short diameter of tumor deposits in LNM required to reach a detection rate of 50% and 90% was estimated to be ≥ 2.3 mm and ≥ 4.5 mm, respectively. Conclusion: In men with biochemical PCa-relapse and positive PSMA-PET/CT, PET/CT detects metastatic affected anatomical regions with high accuracy at a main region and at a subregion-level. If the decision for salvage-LND is prompted by a positive PSMA-PET/CT, the size of metastases is crucial for accurate detection of affected regions. All LNM showed a clear PSMA-expression in the immunohistochemistry. Further studies need to investigate how to translate the high anatomical correlation observed between PET/CT and surgical findings into optimal approaches for target salvage-LND.

Prostatic urethral lift vs transurethral resection of the prostate: 2-year results of the BPH6 prospective, multicentre, randomized study

To compare prostatic urethral lift (PUL) with transurethral resection of the prostate (TURP) with regard to symptoms, recovery experience, sexual function, continence, safety, quality of life, sleep and overall patient perception.

Ultra-mini PCNL versus flexible ureteroscopy: a matched analysis of treatment costs (endoscopes and disposables) in patients with renal stones 10–20 mm

PurposeLatest publications state equal efficacy of a recently introduced new percutaneous technique (“ultra-mini PCNL”, UMP) and flexible ureteroscopy (fURS) in the treatment of medium-size urinary stones. Today we face challenges concerning cost-effectiveness and reduction of in-hospital length of stay. In this retrospective study, we compare clinical outcome parameters and costs of treatment (endoscopes and disposables) of both techniques.MethodsThirty patients treated by UMP at two tertiary university centres were matched to 30 fURS patients from previously recorded databases. Data analysis included operating time, length of stay, stone-free rates (SFR), complications (>Clavien II), ancillary procedures (presurgical ureteral stenting, secondary ureteral stenting or placement of a nephrostomy tube, secondary procedures) and costs for disposable materials and instruments (endoscopes, as calculated per procedure).ResultsWe found no significant differences in operating times (UMP vs. fURS: 121/102xa0min), hospital length of stay (2.3/2.0xa0days), SFR (84/87xa0%) and complications (7/7xa0%). Costs for disposable materials and endoscopes were 656 euro (UMP) and 1,160 euro (fURS) per procedure.ConclusionsUMP and fURS are both safe and effective in the treatment of medium-size urinary stones. Costs for endoscopes and disposable materials are significantly lower in UMP.

Automated Analysis of Urinary Stone Composition Using Raman Spectroscopy: Pilot Study for the Development of a Compact Portable System for Immediate Postoperative Ex Vivo Application

PURPOSEnWe evaluate a compact portable system for immediate automated postoperative exxa0vivo analysis of urinary stone composition using Raman spectroscopy. Analysis of urinary stone composition provides essential information for the treatment and metaphylaxis of urolithiasis. Currently infrared spectroscopy and x-ray diffraction are used for urinary stone analysis. However, these methods may require complex sample preparation and costly laboratory equipment. In contrast, Raman spectrometers could be a simple and quick strategy for immediate stone analysis.nnnMATERIALS AND METHODSnPure samples of 9 stone components and 159 human urinary calculi were analyzed by Raman spectroscopy using a microscope coupled system at 2 excitation wavelengths. Signal-to-noise ratio, peak positions and the distinctness of the acquired Raman spectra were analyzed and compared. Background fluorescence was removed mathematically. Corrected Raman spectra were used as a reference library for automated classification of native human urinary stones (50). The results were then compared to standard infrared spectroscopy.nnnRESULTSnSignal-to-noise ratio was superior at an excitation wavelength of 532xa0nm. An automated, computer based classifier was capable of matching spectra from patient samples with those of pure stone components. Consecutive analysis of 50 human stones demonstrated 100% sensitivity and specificity compared to infrared spectroscopy (for components with more than 25% of total composition).nnnCONCLUSIONSnOur pilot study indicates that Raman spectroscopy is a valid and reliable technique for determining urinary stone composition. Thus, we propose that the development of a compact and portable system based on Raman spectroscopy for immediate, postoperative stone analysis could represent an invaluable tool for the metaphylaxis of urolithiasis.

Single‑Incision Transumbilical Surgery (SITUS) versus Single‑Port Laparoscopic Surgery and conventional laparoscopic surgery: a prospective randomized comparative study of performance with novices in a dry laboratory

AbstractPurposenTo evaluate the Single-Incision Transumbilical Surgery (SITUS) technique as compared to an established laparoendoscopic single-site surgery (LESS) technique (Single-Port Laparoscopic Surgery, SPLS) and conventional laparoscopy (CLS) in a surgical simulator model.MethodsSixty-three medical students without previous laparoscopic experience were randomly assigned to one of the three groups (SITUS, SPLS and CLS). Subjects were asked to perform five standardized tasks of increasing difficulty adopted from the Fundamentals of Laparoscopic Surgery curriculum. Statistical evaluation included task completion times and accuracy.ResultsOverall performances of all tasks (except precision cutting) were significantly faster and of higher accuracy in the CLS and SITUS groups than in the SPLS group (pxa0=xa00.004 to pxa0<xa00.001). CLS and SITUS groups alone showed no significant difference in performance times and accuracy measurements for all tasks (pxa0=xa00.048 to pxa0=xa00.989).ConclusionsSITUS proved to be a simple, but highly effective technique to overcome restrictions of SPLS. In a surgical simulator model, novices were able to achieve task performances comparable to CLS and did significantly better than using a port-assisted LESS technique such as SPLS. The demonstrated advantages of SITUS may be attributed to a preservation of the basic principles of conventional laparoscopy, such as the use of straight instruments and an adequate degree of triangulation.