[Organoids for the advancement of intraoperative diagnostic procedures]. / Organoide zur Weiterentwicklung der intraoperativen Diagnostik.

In the context of cancer surgery, there is always a trade-off between oncological safety and preservation of function. This is especially true in pelvic surgery due to the close relationship to the pelvic floor muscles, blood supply and nerves. Currently, risk models, preoperative imaging, the surgeon's assessment, and the intraoperative frozen section serve as the basis for decision-making. New imaging techniques and standardization in frozen section have significantly improved this in recent years. However, limitations remain due to time delays as well as more difficult correct anatomical assignment in the follow-up. Alternative intraoperative techniques may overcome this limitation in the future. Patient-derived organoids have emerged as an important new research vehicle in recent years. They are based on tumor stem cells that, under special culture conditions, form three-dimensional replicas of the original tissue. This makes them ideally suited for testing individual system therapies but also as a validation technique for new intraoperative diagnostic procedures. The Research Training Group 2543/I, which is funded by the German Research Foundation, is researching the potential of new diagnostic methods in an interdisciplinary team regarding validation in addition to intraoperative frozen sections.

[BCG-induced (bacillus Calmette-Guérin) abdominal granulomatosis after occult bladder perforation]. / Intraabdominelle BCG-Granulomatose (Bacillus Calmette-Guérin) nach okkulter Blasenperforation.

We present the case of a 57-year-old man who developed an intraperitoneal bladder fistula with BCG-induced (bacillus Calmette-Guérin) abdominal granulomatosis after transurethral resection of a papillary non-muscle invasive bladder cancer and subsequent BCG-instillation therapy. The bladder fistula was eliminated surgically. The detection of Mycobacterium tuberculosis in the operative sample drawings as well as the histological detection of BCG-granuloma led to specific treatment and a report to the responsible health department.

Connection between traumatic frontal intracerebral hemorrhage and lower urinary tract symptoms.

OBJECTIVE: There have been no previous studies of urinary symptoms in patients with traumatic frontal intracerebral hemorrhage. The purpose of this work was to provide first insights into the potential role of traumatic frontal intracerebral hemorrhage in the development of urinary symptoms. This condition is known to cause compression in and around the prefrontal cortex, and we wanted to examine its effect on the micturition center. PATIENTS AND METHODS: Patients with voiding dysfunction (n = 176) were assessed for lower urinary tract symptoms using the International Prostate Symptom Score (IPSS). Out of 176 patients, 52 symptomatic patients with voiding difficulties underwent urodynamic testing. All patients with traumatic frontal intracerebral hemorrhage were treated at the University Medical Center Tuebingen, Germany, and the Azad University of Medical Sciences in Tehran, Iran, between 2017 and 2020. Lower urinary tract symptoms (LUTS) were documented in patients with compression of the frontal lobe due to local hemorrhage. All patients routinely performed Brain CT scans. Brain magnetic resonance (MRI) images of the patients with suspicion of diffuse axonal injuries were additionally performed. Out of 176 treated patients (median age of 49 years), 52 patients with voiding difficulties were evaluated. RESULTS: Urodynamic testing of 52 symptomatic patients revealed detrusor overactivity in 25 (48%), low-compliance bladder in 4 (7.7%), detrusor-sphincter dyssynergia in 20 (38%), and uninhibited sphincter relaxation in 11 patients (21%). There was no significant correlation between the volume of hemorrhage and urinary symptoms (p=0.203, Spearman q=0.726). Frontal intracerebral hemorrhage compressing the pre-frontal cortex influences the micturition center and is responsible for lower urinary tract symptoms. CONCLUSIONS: Hemorrhage of the right or left frontal lobe does have a direct relationship with incontinence which completely disappeared in 85% of the patients within 9 months.

The connection between frontal lobe brain tumors and lower urinary tract symptoms - Series of 347 patients.

OBJECTIVE: The present study aimed to provide an early insight into the effect of intra-axial frontal lobe tumors on the micturition center and its potential role in producing compression in and around the prefrontal cortex. PATIENTS AND METHODS: A total of 149 symptomatic patients were selected for urodynamic testing. The study sample included all patients with intra-axial frontal lobe tumors treated at two locations: the University Medical Center Tuebingen (Germany), and Azad University of Medical Sciences (Iran) between 2017 and 2020. Lower urinary tract symptoms (LUTS) were recorded in patients with frontal lobe compression due to local tumor growth. The symptomatic patients had brain magnetic resonance (MRI) images taken to examine for possible lesions. RESULTS: The treated patients (149 patients with a median age of 55 years) were evaluated using computer urodynamic investigation and voiding diaries. The results of urodynamic testing of 149 symptomatic patients showed detrusor over-activity in 82 (55%) patients, dyssynergia of detrusor-sphincter in 67 (45%) patients, uninhibited sphincter relaxation in 40 (27%) patients, and low-compliance bladder in 21 (14%) patients. There was no significant correlation found between tumor size and urinary symptoms (p = 0.103, Spearman q = 0.826). CONCLUSIONS: Frontal intra-axial tumors compressing and infiltrating the prefrontal cortex influence the micturition center and produce lower urinary tract symptoms. The tumors of the right frontal lobe were directly associated with incontinence, which was completely disappeared in 70% of the patients within 2 years.

Urethroplasty performed with an autologous urothelium-vegetated collagen fleece to treat urethral stricture in the minipig model.

INTRODUCTION AND OBJECTIVE: Tissue-engineered materials in urethral reconstructive surgeries are a promising field for innovative therapy. Collagen matrices increase stability of cell-based implants and can promote viability and proliferation of urothelial cells. In this study, a collagen type I-based cell carrier (CCC) with stratified multi-layer autologous urothelium was used for urethroplasty after induction of urethral stricture in eight minipigs. MATERIALS AND METHODS: Minipigs underwent surgical procedures to induce urethral stricture by thermocoagulation. Simultaneously, bladder tissue was harvested. Urothelial cells were expanded, labeled with PKH26 and seeded onto CCC in high density. 3 weeks after strictures were induced and verified by urethrography, minipigs underwent urethroplasty using the seeded CCC. Two animals were euthanized after 1, 2, 4, and 24 weeks. Urethras were histologically examined for integration and survival of seeded CCC. In vivo phenotype of multi-layered urothelium matrix constructs was characterized via immunofluorescence staining with pancytokeratin, CK20, p63, E-cadherin and ZO-1. RESULTS: Seeded CCCs showed excellent stability and suturability after manipulation and application. Transplanted cells were detected using positive PKH26 fluorescence up to 6 months after labeling. Urothelium matrix implants integrated well into the host tissue without sign of inflammation. Animals showed no sign of rejection or stricture recurrence (urethrography) at any time during experimental period. Immunofluorescence analysis confirmed epithelial phenotype, junction formation and differentiation after 2 weeks. CONCLUSION: CCC can be suitable for urologic reconstructive surgeries and represents a promising option for clinical application. Longer follow-up results are required to exclude re-occurrence of stricture reformation.

[Influence of immunomodulators on urological imaging]. / Einfluss von Immunmodulatoren auf die urologische Bildgebung.

BACKGROUND: Immune checkpoint inhibitors (ICI) have led to great advances in the therapy of metastatic renal cell and urothelial carcinoma. Currently ICI are approved for the first-line therapy of cisplatin-unfit patients (Atezolizumab, Pembrolizumab) and second-line therapy in patients with metastasized urothelial cancer (Atezolizumab, Nivolumab, Pembrolizumab). For the therapy of metastasized RCC, Nivolumab is approved as a second-line therapy and in combination with the CTLA­4 antibody Ipilimumab as a first-line therapy. OBJECTIVES: What does the optimized radiological follow-up and therapy response assessment for ICI, which differ in their pathways from common chemotherapeutics and anti-angiogenetic drugs, look like? What strategies are needed to meet the upcoming challenges concerning interpretation of the acquired images? METHODS: A systematic literature search was carried out for urothelial and renal cell carcinoma. RESULTS: Immune-related response criteria have been introduced to better characterize the imaging changes occurring under ICI, as monitoring response to immunotherapy still relies on RECIST. CONCLUSIONS: To properly identify and predict response after treatment with ICI, additional studies with long-term follow-ups are needed. Because of the growing use of ICI, radiologists and urologist should be familiar with common imaging findings (such as pseudo progress) under immunotherapy to correctly interpret these findings in daily routine.

First report of robot-assisted transperineal fusion versus off-target biopsy in patients undergoing repeat prostate biopsy.

PURPOSE: To clarify the value of targeted versus off-target biopsies in men with a suspicion of prostate cancer (PC) and a visible lesion in multi-parametric magnetic resonance imaging (mpMRI) using transperineal robot-assisted biopsy. METHODS: Fifty-five consecutive men with one non-palpable suspicious lesion in mpMRI after negative 12-core transrectal ultrasound-guided biopsy were enrolled in 2014-2015. Lesions were scored using the Prostate Imaging Reporting and Data System. A robot-assisted system was utilized to collect four robot-assisted targeted transperineal biopsy cores (RA-TB) within the lesion using mpMRI-TRUS elastic fusion. Untargeted transperineal 14-core biopsy was performed only outside the lesion (RA-UB). Histological grade was compared in biopsies and available prostatectomy specimens. RESULTS: Overall, 34 of 55 patients (62%) were diagnosed with PC based on biopsy. 85% of cancers were clinically significant PC (csPC) defined as GS ≥ 7. 85% of biopsy-proven cancers were detected with RA-TB alone. RA-UB identified only one additional patient with csPC and lead to upgrading in five biopsy cases (14.7%). Pathological evaluation of 14 prostatectomy specimens showed upgrading in 2 patients (14.3%), while all other patients were correctly classified by RA-TB without need of additional RA-UB. Mean procedure duration was 43 (±6) min, and only minor complications according to Clavien-Dindo were recorded during 30-day follow-up. CONCLUSIONS: This is the first report of transperineal robot-assisted elastic mpMRI-TRUS fusion biopsy. RA-TB of positive MR lesions enabled reliable detection of csPC, while RA-UB in MRI-negative regions is of minor importance.

Liposarcoma of the Spermatic Cord: Impact of Final Surgical Intervention--An Institutional Experience.

BACKGROUND: Paratesticular liposarcomas are almost always mistakenly diagnosed as inguinal hernias subsequently followed by inadequate operation. METHODS: 14 consecutive patients with paratesticular liposarcoma were retrospectively reviewed. Preoperative management was evaluated. Disease-free and overall survival were determined. RESULTS: In 11 patients primary and in 3 patients recurrent liposarcoma of the spermatic cord were diagnosed. Regarding primary treatment in primary surgical intervention resection was radical (R0) in 7 of 14 (50%) patients, marginal (R1) in 6 (43%) patients, and incomplete with macroscopic residual tumour (R2) in 1 (7%) patient. Primary treatment secondary surgical intervention was performed in 4 patients: resection was radical (R0) in 3 (75%) patients and marginal (R1) in 1 (25%) patient. Regarding secondary treatment in recurrent disease resection was marginal (R1) in 3 patients (100%). Final histologic margins were negative in 10 patients with primary disease (71%) and positive in 4 patients with subsequent recurrent disease. After radical resection disease-free survival rates at 3 years were 100%. Overall survival at 4.5 years (54 (18-180) months) was 64%. CONCLUSION: An incomplete first surgical step increases the number of positive margins leading to local recurrences and adverse prognoses. Aggressive surgery should be attempted to attain 3-dimensional negative margins.

[Urinary bladder injuries. Diagnosis and treatment]. / Harnblasenverletzungen. Diagnostik und Therapie.

BACKGROUND: Injuries of the urinary bladder can be associated with blunt and penetrating abdominal or pelvic trauma. In addition, they can be an iatrogenic complication in open, laparoscopic, and endoscopic urogenital or abdominal surgery. OBJECTIVES: The present article reviews relevant causes of bladder injuries and the subsequent diagnostic and treatment modalities.

[Cell-based therapy to treat stress urinary incontinence: which cell type at what cost?]. / Zellbasierte Therapie der Belastungsinkontinenz: Welche Zelle zu welchen Kosten?

In Germany, 6-8 million woman and men suffer urinary incontinence, which represents 12.5 % of the population. It is estimated that by the middle of this century, it will increase to almost 30 %. The primary reason will be primarily related to the aging population but also to patient awareness and seeking a solution. In addition to the cost which is covered by the health insurance, the patient will spend more than half a billion euro/year out-of-pocket, not to mention the social stigma associated with urinary incontinence. The current common treatment options are symptomatic but do not restore functionality. One option might be tissue engineering or stem cell therapy. This article describes the likelihood that this therapy will change the approach in treating stress urinary incontinence. Boundaries and legal aspects are highlighted as well as approximated cost. These treatment costs might be currently higher than the standard treatment options, but the investment to reduce these costs are paid indirectly by society.

[Stem cell therapy and tissue engineering in regenerative urology]. / Stammzelltherapie und "Tissue Engineering" in der regenerativen Urologie.

BACKGROUND: So far there is no clinically established, effective tissue engineering therapy for dysfunction or defects of the lower urinary tract. The concentration of experimental data, initial clinical studies and individual case reports underlines that stem cell treatment for bladder storage and voiding problems, erectile dysfunction and other urothelial defects of the lower urinary tract could close the gap between individualized therapy and potential biomedical applications. RESULTS: As a result of fundamental research work over the last decade a characterization of various stem cell populations and evaluation of different urological therapy options could be performed. Thereby, aspects of optimal administration, migration, secretion of bioactive factors and stage of differentiation of stem cells with respect to an improved efficiency of treatment were investigated. Because successful tissue regeneration depends on angiogenesis and innervation, particular attention was paid to these important factors. CONCLUSIONS: Various clinical indications for stem cell treatment and tissue reconstruction that may be required after radical prostatectomy, such as stress urinary incontinence, urethral reconstruction and erectile dysfunction have materialized and are currently being verified in preclinical studies and phase I trials.

Different surgical approaches for stress urinary incontinence in women.

Stress urinary incontinence (SUI) constitutes involuntary voiding as a consequence of rising intra-abdominal pressure caused by sphincter weakness. In recent years studies were published according to surgical SUI management evaluating and comparing therapy options and outcomes. Therapy options were evaluated using a Medline search, including only publications in English between 2000-2012. Key words used were: SUI, conservative and surgical treatment, midurethral sling, colposuspension. Surgical treatment options demonstrate significantly better results than conservative treatment. MUS demonstrate better subjective and objective cure rates than colposuspension; it is less invasive and more cost-effective. First line SUI therapy such as RP MUS and TVT seem to be favored when compared to transobturator techniques. Retropubic and transobturator MUS showed equivalent objective and subjective success rates. Open colposuspension is an effective treatment possibility for recurrent SUI after failed MUS. TVT, compared with other MUS, seems to show slightly better cure rates. but perioperative complications appear to be similar. Long-term results (>10 years) of repeated SUI surgery showed that the Burch procedure had the lowest 9-year cumulative incidence of repeat SUI surgery. Mini-sling techniques may be underestimated but long-time results are pending and closer monitoring of the adverse event profile must be carried out. MUS are first choice in the treatment of SUI, of which TVT, has the best cure rate. Colpussupension continues to have its place in recurrent SUI. The new mini-MUS needs a longer follow-up for final evaluation.

[Urinary incontinence in the elderly: what can and should be done?]. / Inkontinenz im Alter: Was kann und soll man tun?

The demographic development of society shows a clear increase in the elderly population in the coming decades, which will result in an increasing prevalence of urinary incontinence. Diagnosis and treatment of many patients is not carried out for a myriad of reasons and thus incontinence care is often inadequate. A detailed medical history is the basis of identification of the problem and underpins the effective diagnostic and therapeutic management of the problem. In this context, the algorithms based on the national and international guidelines and age-specific characteristics should be considered. The initial focus should be on conservative management. In a few cases of elderly patients, invasive diagnostics using urodynamics or cystoscopy might be indicated. The increased use of medication in the elderly both from an etiological and therapeutic point of view, especially in terms of drug/drug interactions requires special consideration. In particular cognitive impairment using pharmacological approaches should be avoided. Although incontinence surgery of the patient applies less often with increasing age it still plays a role in the appropriate selection of treatment.

Prostatic peripheral nerve distribution may impact the functional outcome of nerve-sparing prostatectomy.

PURPOSE: To study microscopic patterns of remaining peripheral nerves (PN) after nerve-sparing (NS) radical prostatectomy (RP) and possible consequences for nerve preparation. METHODS: Specimens from 27 patients (7 = non-NSRP, 20 = unilateral NS) were examined. Sections were investigated for PN content by immunoassaying. 120 whole-mounted slides were divided into four sectors, and extracapsular nerves were counted; the mean posterior/anterior ratio was calculated. Calculated ratios were correlated with the respective volumes of prostatic tissue (PV). After dividing the patient cohort into two subgroups, shared by the median value of the posterior/anterior nerve ratios, the absolute PN contents on the anterior surface of the NS sides were compared. RESULTS: Anatomical posterior nerve percentage in non-NS aspects ranged from 0.0-100.0 to 26.7-94.6% with a mean of 66.60 ± 25.4% and 68.83 ± 16.0% (>/<200 µm, respectively). Individual ratios from two nerve categories showed significant correlation (P < 0.008). Mean posterior ratios were 83.04/79.68 and 39.21/56.00, respectively. After unilateral NS, 3.17-fold (2.25 vs. 0.71 nerves, P = 0.05) and 2.26-fold (21.54 vs. 9.53, P = 0.08) nerve fibers were resected in the anterior area in comparison with type A. After unilateral NS, the variation impact on the anterior nerve content of the NS side could be demonstrated. CONCLUSIONS: The amounts of nerves localized on the anterior prostate after RP vary interindividually. Saving only a minor part of the anterior areas may have an impact on the quantity of excised nerves adjacent to the specimen and impair postoperative functional results. Especially for those patients without a major posterolateral bundle distribution, surgeons should adapt the procedure and start nerve preservation more anteriorly to maximize the probability of satisfactory postoperative functional results.

[Unconventional treatment procedures of the bladder in paraplegia and myelomeningocele]. / Behandlungsverfahren der Blase bei Querschnittlähmung und Myelomeningozele.

The established treatment of neurogenic lower urinary tract dysfunction (NLUTD) in patients with spinal cord injury (SCI) or meningomyelocele (MMC) is mainly conservative and is aimed at the lower urinary tract. For example, oral antimuscarinic medication is the standard treatment of neurogenic detrusor overactivity. Recently, however, treatment aiming directly or indirectly at the innervation of the urinary tract has gained increasing attention. Current evidence does not justify the use of nerve rerouting but the existing preliminary data are more promising for MMC patients than for those with SCI. Sacral neuromodulation is already a therapeutic option for incomplete SCI patients. Initial data from a pilot study indicate that in patients with complete SCI implementation in the spinal shock phase may prevent the development of NLUTD. Licensing of onabotulinum toxin A (Botox®) facilitated its clinical use for treating NLUTD but it is limited to the indication of neurogenic detrusor overactivity incontinence with a dosage of 200 IU. The mentioned unconventional treatments, although discussed controversially, are promising future treatment options for NLUTD.

[New treatment strategies for male lower urinary tract symptoms]. / Neue Behandlungskonzepte von Symptomen des unteren Harntraktes beim Mann.

For patients with lower urinary tract symptoms (LUTS), α1-adrenoreceptor inhibitors and 5-alpha reductase inhibitors as well as their combination are considered the gold standard. In addition, anticholinergic agents are being introduced as monotherapy or in combination with α1-adrenocepetor inhibitors for patients with predominant storage disorders. Phosphodiesterase 5 (PDE5) inhibitors are often the best option for patients with LUTS who also suffer from erectile dysfunction. Recently, novel treatment options have been presented and intraprostatic injection of various agents, such as botulinum toxin A, NX-1207 and PRX302 has shown promising initial results. In addition, innovative minimally invasive treatment options, such as UroLift® appear to be efficacious and safe in this patient cohort. Particular emphasis should be laid on patients with LUTS and concomitant sexual disorders.

Akt signalling parameters are different in oncocytomas compared to renal cell carcinoma.

PURPOSE: Renal oncocytomas are assigned as benign tumours, and their detailed molecular mechanism is poorly characterised. Activation of the PKB/Akt pathway is assumed to contribute to the pathogenesis and progression of malignant disease. For oncocytomas, hardly any data are available for Akt signalling parameters. Aim of the present work was to determine the alterations of Akt parameters PTEN, phosphorylated Akt (p-Akt) and p27(Kip1) in oncocytoma to better understand the dedifferentiation of renal tumours. METHODS: By tissue microarray analysis 15 oncocytoma, 18 clear cell renal cell carcinoma (ccRCC) and the corresponding benign tissue were investigated. Significant expression differences between PTEN, p-Akt and p27(Kip1) were determined by immunohistochemistry using One-way ANOVA with all pairs Tukey-Kramer as post hoc analyses. To investigate Akt parameter interactions in the oncocytoma, linear regression analyses were performed. RESULTS: Expression of all proteins was significantly different between the groups and in all groups the lowest for oncocytoma: PTEN: 32.9 ± 13.0 versus 75.5 ± 8.0 versus 123.7 ± 8.8; p < 0.001 for oncocytoma, benign parenchyma and ccRCC and 2.7 ± 1.2 versus 40.8 ± 9.5 versus 143.6 ± 12.2; p < 0.001 for p27(Kip1). p-Akt expression was significantly different between oncocytoma and ccRCC (67.3 ± 15.7 vs. 144.0 ± 26.6; p < 0.05). CONCLUSION: All three investigated parameters were the lowest in oncocytoma when compared to ccRCC. Expression of PTEN and p27(Kip1) seems to be exceedingly associated with malignant conditions of ccRCC. These findings might contribute to the understanding of tumorous signalling of the PKB/Akt axis in renal tumours.

[Second-line therapy of idiopathic detrusor overactivity. Sacral neuromodulation and botulinum toxin A]. / Second-line-Therapie der idiopathisch überaktiven Blase. Sakrale Neuromodulation und Botulinumtoxin A.

The syndrome of idiopathic overactive bladder (I-OAB) impairs quality of life for the affected individuals. Conservative treatment options such as antimuscarinics are not always effective, and resulting side effects can lead the patient to stop treatment. In recently years, minimally invasive and reversible sacral neuromodulation and botulinum toxin A have become available. Currently, the approved treatment option for I-OAB that is recommended by the International Consultation on Incontinence is sacral neuromodulation by InterStim therapy. This article gives an overview of the present clinical evidence on the effectiveness and reliability of these two treatment modalities as well as the current significance of sacral neuromodulation and botulinum toxin A for the second-line treatment of adult I-OAB.

[Treatment of female and male stress urinary incontinence. Current aspects]. / Therapie der Belastungsharninkontinenz bei Frau und Mann. Aktuelle Aspekte.

Treatment options for female and male stress urinary incontinence are continually being developed. In female patients, the effectiveness of suburethral slings has been demonstrated to be equal to classical retropubic Burch colposuspension. A minimally invasive procedure has been approximated through a stepwise enhancement of the retropubic approach, to the transobturator approach, and, finally, to the single-incision sling approach. As a result, surgical options with gender-specific differences have emerged; increasingly different sling systems have been established for male stress urinary incontinence. Further individualization of surgical incontinence treatment can be achieved based on adjustable sling devices. Thus, the use of bulking agents for stress urinary incontinence has been abandoned, and therapeutic options besides the artificial urinary sphincter are now available.