Xenogenic Application of Human Placenta-Derived Mesenchymal Stromal Cells in a Porcine Large Animal Model.

In animal models, cell therapies for different diseases or injuries have been very successful. Preclinical studies with cells aiming at a stroke, heart attack, and other emergency situations were promising but sometimes failed translation in clinical situations. We, therefore, investigated if human placenta-derived mesenchymal stromal cells can be injected in pigs without provoking rejection to serve as a xenogenic transplantation model to bridge preclinical animal studies to more promising future preclinical studies. Male human placenta-derived mesenchymal stromal cells were isolated, expanded, and characterized by flow cytometry, in vitro differentiation, and quantitative reverse-transcription polymerase chain reaction to prove their nature. Such cells were injected into the sphincter muscle of the urethrae of female pigs under visual control by cystoscopy employing a Williams needle. The animals were observed over 7 days of follow-up. Reactions of the host to the xenogeneic cells were explored by monitoring body temperature, and inflammatory markers including IL-1ß, CRP, and haptoglobin in blood. After sacrifice on day 7, infiltration of inflammatory cells in the tissue targeted was investigated by histology and immunofluorescence. DNA of injected human cells was detected by PCR. Upon injection in vascularized porcine tissue, human placenta-derived mesenchymal stromal cells were tolerated, and systemic inflammatory parameters were not elevated. DNA of injected cells was detected in situ 7 days after injection, and moderate local infiltration of inflammatory cells was observed. The therapeutic potential of human placenta-derived mesenchymal stromal cells can be explored in porcine large animal models of injury or disease. This seems a promising strategy to explore technologies for cell injections in infarcted hearts or small organs and tissues in therapeutically relevant amounts requiring large animal models to yield meaningful outcomes.

Production of Proliferation- and Differentiation-Competent Porcine Myoblasts for Preclinical Studies in a Porcine Large Animal Model of Muscular Insufficiency.

Muscular insufficiency is observed in many conditions after injury, chronic inflammation, and especially in elderly populations. Causative cell therapies for muscle deficiencies are not state of the art. Animal models to study the therapy efficacy are, therefore, needed. We developed an improved protocol to produce myoblasts suitable for pre-clinical muscle therapy studies in a large animal model. Myoblasts were isolated from the striated muscle, expanded by employing five different protocols, and characterized on transcript and protein expression levels to determine procedures that yielded optimized regeneration-competent myoblasts and multi-nucleated myotubes. We report that swine skeletal myoblasts proliferated well under improved conditions without signs of cellular senescence, and expressed significant levels of myogenic markers including Pax7, MyoD1, Myf5, MyoG, Des, Myf6, CD56 (p ≤ 0.05 each). Upon terminal differentiation, myoblasts ceased proliferation and generated multi-nucleated myotubes. Injection of such myoblasts into the urethral sphincter complex of pigs with sphincter muscle insufficiency yielded an enhanced functional regeneration of this muscle (81.54% of initial level) when compared to the spontaneous regeneration in the sham controls without myoblast injection (67.03% of initial level). We conclude that the optimized production of porcine myoblasts yields cells that seem suitable for preclinical studies of cell therapy in a porcine large animal model of muscle insufficiency.

Hemangioma of the Urinary Bladder: A Brief Narrative Review of Their Diagnosis, Histology, and Treatment Options.

BACKGROUND: Hemangioma of the urinary bladder is a rare benign tumor. Although benign, their presenting symptoms are alarming for both patients and doctors, and their rarity makes them challenging to correctly diagnosis and treat. This review paper summarizes current knowledge about hemangioma of the urinary bladder, treatment options, and follow-up modalities. SUMMARY: After the kidney, the bladder is the second most common location of hemangiomas in the urinary tract. There is painless gross hematuria on clinical presentation once the lesion has eroded the urothelium. Magnetic resonance imaging (MRI) has been reported to be valuable in diagnosing soft-tissue hemangiomas. Cystoscopic findings of a sessile, blue, multilocular mass suggest hemangioma. Most tumors are solitary, smaller than 3 cm, and have smooth or irregular surfaces. Histologically, lesions comprise numerous proliferative capillaries with thin-walled, dilated, blood-filled vessels lined with flattened endothelium. The treatment of patients with hemangioma has been controversial. It depends on the tumor size and the degree of penetration. The prognosis of these tumors is excellent. KEY MESSAGES: Despite the widespread use of MRI, CT, and endoscopy in evaluating hematuria, hemangioma remains one of the rarest bladder tumors. Moreover, only a histological examination can confirm the diagnosis. Transurethral resection, fulguration, and YAG laser ablation are standard treatments for small tumors. In terms of follow-up, cystoscopy after 6 months of treatment helps assess recurrence. In addition, MRI is a practical, noninvasive technique for follow-up of small hemangiomas.

Female Hyperplastic PSA-Positive Prostate Tissue in the Bladder Neck.

INTRODUCTION: We report a rare case of Skene's gland hyperplasia where the serum prostate-specific antigen (PSA) level was measurable. CASE PRESENTATION: The patient was a 91-year-old woman with a suspected bladder mass at the bladder trigone. Cystoscopy revealed a suspected lesion and an obstructed anterior bladder neck with a large mass located from a "7 o'clock" to "11 o'clock" area. The photodynamic diagnosis was negative. Transurethral subtotal resection of the mass was performed. The serum PSA level at the third postoperative day was 0.08 ng/mL. Postoperative cystography showed no contrast media extravasation. Thus, histopathology revealed massive adenomyomatous hyperplasia of the Skene's gland, as well as nondysplastic urothelium and glandular and squamous epithelium. Immunohistochemistry showed strong PSA and NKX3.1 positivity, confirming the diagnosis of "female prostate." FISH analysis showed only green signals that confirm an XX karyotype. In follow-up to 17 months, there was no disease recurrence or need for a urinary catheter. CONCLUSION: Effective therapeutic strategies for these lesions are unknown due to the absence of reported cases. Given the patient's age, we assumed that bladder neck resection by transurethral resection with a controlled level of serum PSA would be a suitable therapeutic approach.

Cell Therapy by Mesenchymal Stromal Cells Versus Myoblasts in a Pig Model of Urinary Incontinence.

The leading cause of stress urinary incontinence (SUI) in women is the urethral sphincter muscle deficiency caused by mechanical stress during pregnancy and vaginal delivery. In men, prostate cancer surgery and injury of local nerves and muscles are associated with incontinence. Current treatment often fails to satisfy the patient's needs. Cell therapy may improve the situation. We therefore investigated the regeneration potential of cells in ameliorating sphincter muscle deficiency and UI in a large animal model. Urethral sphincter deficiency was induced surgically in gilts by electrocautery and balloon dilatation. Adipose tissue-derived stromal cells (ADSCs) and myoblasts from Musculus semitendinosus were isolated from male littermates, expanded, characterized in depth for expression of marker genes and in vitro differentiation, and labeled. The cells were injected into the deficient sphincter complex of the incontinent female littermates. Incontinent gilts receiving no cell therapy served as controls. Sphincter deficiency and functional regeneration were recorded by monitoring the urethral wall pressure during follow-up by two independent methods. Cells injected were detected in vivo during follow-up by transurethral fluorimetry, ex vivo by fluorescence imaging, and in cryosections of tissues targeted by immunofluorescence and by polymerase chain reaction of the sex-determining region Y (SRY) gene. Partial spontaneous regeneration of sphincter muscle function was recorded in control gilts, but the sphincter function remained significantly below levels measured before induction of incontinence (67.03% ± 14.00%, n = 6, p < 0.05). Injection of myoblasts yielded an improved sphincter regeneration within 5 weeks of follow-up but did not reach significance compared to control gilts (81.54% ± 25.40%, n = 5). A significant and full recovery of the urethral sphincter function was observed upon injection of ADSCs within 5 weeks of follow-up (100.4% ± 23.13%, n = 6, p < 0.05). Injection of stromal cells provoked slightly stronger infiltration of CD45pos leukocytes compared to myoblasts injections and controls. The data of this exploratory study indicate that ADSCs inherit a significant potential to regenerate the function of the urethral sphincter muscle.

Regulation of Immune Checkpoint Antigen CD276 (B7-H3) on Human Placenta-Derived Mesenchymal Stromal Cells in GMP-Compliant Cell Culture Media.

Therapies utilizing autologous mesenchymal cell delivery are being investigated as anti-inflammatory and regenerative treatments for a broad spectrum of age-related diseases, as well as various chronic and acute pathological conditions. Easily available allogeneic full-term human placenta mesenchymal stromal cells (pMSCs) were used as a potential pro-regenerative, cell-based therapy in degenerative diseases, which could be applied also to elderly individuals. To explore the potential of allogeneic pMSCs transplantation for pro-regenerative applications, such cells were isolated from five different term-placentas, obtained from the dissected maternal, endometrial (mpMSCs), and fetal chorion tissues (fpMSCs), respectively. The proliferation rate of the cells in the culture, as well as their shape, in vitro differentiation potential, and the expression of mesenchymal lineage and stem cell markers, were investigated. Moreover, we studied the expression of immune checkpoint antigen CD276 as a possible modulation of the rejection of transplanted non-HLA-matched homologous or even xeno-transplanted pMSCs. The expression of the cell surface markers was also explored in parallel in the cryosections of the relevant intact placenta tissue samples. The expansion of pMSCs in a clinical-grade medium complemented with 5% human platelet lysate and 5% human serum induced a significant expression of CD276 when compared to mpMSCs expanded in a commercial medium. We suggest that the expansion of mpMSCs, especially in a medium containing platelet lysate, elevated the expression of the immune-regulatory cell surface marker CD276. This may contribute to the immune tolerance towards allogeneic pMSC transplantations in clinical situations and even in xenogenic animal models of human diseases. The endurance of the injected comparably young human-term pMSCs may promote prolonged effects in clinical applications employing non-HLA-matched allogeneic cell therapy for various degenerative disorders, especially in aged adults.

Stress Urinary Incontinence: An Unsolved Clinical Challenge.

Stress urinary incontinence is still a frequent problem for women and men, which leads to pronounced impairment of the quality of life and withdrawal from the social environment. Modern diagnostics and therapy improved the situation for individuals affected. But there are still limits, including the correct diagnosis of incontinence and its pathophysiology, as well as the therapeutic algorithms. In most cases, patients are treated with a first-line regimen of drugs, possibly in combination with specific exercises and electrophysiological stimulation. When conservative options are exhausted, minimally invasive surgical therapies are indicated. However, standard surgeries, especially the application of implants, do not pursue any causal therapy. Non-absorbable meshes and ligaments have fallen into disrepute due to complications. In numerous countries, classic techniques such as colposuspension have been revived to avoid implants. Except for tapes in the treatment of stress urinary incontinence in women, the literature on randomized controlled studies is insufficient. This review provides an update on pharmacological and surgical treatment options for stress urinary incontinence; it highlights limitations and formulates wishes for the future from a clinical perspective.

A Protocol for Organoids from the Urine of Bladder Cancer Patients.

This study investigates the feasibility of establishing urine-derived tumor organoids from bladder cancer (BC) patients as an alternative to tissue-derived organoids. BC is one of the most common cancers worldwide and current diagnostic methods involve invasive procedures. Here, we investigated the potential of using urine samples, which contain exfoliated tumor cells, to generate urine-derived BC organoids (uBCOs). Urine samples from 29 BC patients were collected and cells were isolated and cultured in a three-dimensional matrix. The establishment and primary expansion of uBCOs were successful in 83% of the specimens investigated. The culturing efficiency of uBCOs was comparable to cancer tissue-derived organoids. Immunohistochemistry and immunofluorescence to characterize the uBCOs exhibited similar expressions of BC markers compared to the parental tumor. These findings suggest that urine-derived BC organoids hold promise as a non-invasive tool for studying BC and evaluating therapeutic responses. This approach could potentially minimize the need for invasive procedures and provide a platform for personalized drug screening. Further research in this area may lead to improved diagnostic and treatment strategies for BC patients.

Effects of Scaffolds on Urine- and Urothelial Carcinoma Tissue-Derived Organoids from Bladder Cancer Patients.

Organoids are three-dimensional constructs generated by placing cells in scaffolds to facilitate the growth of cultures with cell-cell and cell-matrix interactions close to the in vivo situation. Organoids may contain different types of cells, including cancer cells, progenitor cells, or differentiated cells. As distinct culture conditions have significant effects on cell metabolism, we explored the expansion of cells and expression of marker genes in bladder cancer cells expanded in two different common scaffolds. The cells were seeded in basement membrane extract (BME; s.c., Matrigel®) or in a cellulose-derived hydrogel (GrowDex®, GD) and cultured. The size of organoids and expression of marker genes were studied. We discovered that BME facilitated the growth of significantly larger organoids of cancer cell line RT112 (p < 0.05), cells from a solid tumor (p < 0.001), and a voiding urine sample (p < 0.001). Expression of proliferation marker Ki76, transcription factor TP63, cytokeratin CK20, and cell surface marker CD24 clearly differed in these different tumor cells upon expansion in BME when compared to cells in GD. We conclude that the choice of scaffold utilized for the generation of organoids has an impact not only on cell growth and organoid size but also on protein expression. The disadvantages of batch-to-batch-variations of BME must be balanced with the phenotypic bias observed with GD scaffolds when standardizing organoid cultures for clinical diagnoses.

How [18F]-FDG-PET/CT Affects Clinical Management of Patients with Germ Cell Tumors in the Real World.

OBJECTIVE: The aim of this study was to evaluate the impact of PET/CT on clinical management of patients with germ cell tumors (GCTs) conducted in a real-world setting, including avoidance of invasive procedures, additional diagnostic imaging, and changes in treatment. METHODS: Patients with GCTs were prospectively enrolled into a PET/CT registry study between May 2013 and April 2021. Intended patient management prior and after PET/CT was documented using standardized questionnaires. Changes in oncologic staging and clinical management after PET/CT were recorded, including planned treatment and planned additional diagnostics. RESULTS: Forty-three male patients with GCTs were included consecutively in this study. After PET/CT, oncologic staging changed in 22/43 patients (51%), with upstaging in seven cases (16%), downstaging in ten cases (23%), and cancer relapse in five cases (11%). The number of patients with intended curative treatment remained stable, while a considerable change in intended therapeutic intervention was noted after PET/CT, with an increase in planned chemotherapy from three to eleven patients and a decrease in planned surgical resection from eleven to two patients. In addition, PET/CT contributed to preventing patients from intended invasive procedures including biopsy and surgery in 8/43 (19%) cases and from additional diagnostic procedures in 25 (58%) cases. CONCLUSION: With the use of FDG-PET/CT as a tool to guide patient management in GCTs, we observed a notable impact on clinical staging and a consequent reduction in the need for additional invasive and diagnostic procedures. These findings are expected to be even more consequential in the future as treatment modalities improve and the life expectancy of GCT patients further increases. KEY POINTS: PET/CT considerably influences the clinical stage of GCT patients. PET/CT has remarkable influence on the choice of therapeutic interventions and reduces additional diagnostic procedures.

A Peritoneal Purse-String Suture Prevents Symptomatic Lymphoceles in Retzius-Sparing Robot-Assisted Radical Prostatectomy.

BACKGROUND: The retzius-sparing approach for robotic-assisted radical prostatectomy (RARP) has been increasingly adopted. Symptomatic lymphoceles are a widespread complication of RARP with pelvic lymph node dissection. Here, we present a new technique, the peritoneal purse-string suture (PPSS), that seems to reduce the rate of symptomatic lymphoceles following retzius-sparing RARP with extended pelvic lymph node dissection (ePLND). METHODS: The radical prostatectomy and bilateral lymphadenectomy are performed through three separate peritoneal openings. The PPSS uses a single suture in a way similar to a purse-string suture; the openings of both lymphadenectomy fields are widened, and the rectovesical opening from the prostatectomy is simultaneously closed. This report retrospectively evaluates the perioperative and postoperative outcomes of two consecutive patient cohorts undergoing RARP with ePLND by a single surgeon between May 2015 and June 2019, one cohort prior to introducing PPSS as control (n = 145) and the other after introducing PPSS (n = 91). RESULTS: The two study groups were comparable on baseline characteristics, except ASA. There were no Clavien-Dindo grade IV-V complications, and comparable rates of grade I-III complications. The difference in postoperative lymphocele formation was 22% in PPSS versus 27% in the control group (p = 0.33). The rate of symptomatic lymphoceles was significantly lower in the PPSS group (3% vs. 10%, p = 0.047). CONCLUSION: The PPSS is a feasible procedure that reduces symptomatic lymphoceles in patients undergoing RARP with a retzius-sparing approach.

Uterine allograft removal by total laparoscopic hysterectomy after successful cesarean delivery in a living-donor uterus recipient with uterovaginal agenesis (MRKHS).

PURPOSE: To limit the burden of long-term immunosuppression (IS) after uterus transplantation (UTx), removal of the uterine allograft is indicated after maximum two pregnancies. Hitherto this has required graft hysterectomy by laparotomy. Our objective was to demonstrate, as a proof of concept, the feasibility of less traumatic transplantectomy by total laparoscopic hysterectomy (TLH). PATIENT: A 37-year-old woman with uterovaginal agenesis due to Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) who had undergone neovaginoplasty at age 19 years prior to living-donor (LD) UTx in 10/2019 at age 35 years gave birth to a healthy boy by primary cesarean section in 06/2021. During pregnancy, she developed impaired renal function, with bilateral hydronephrosis, necessitating early allograft removal in 09/2021 to prevent chronic kidney disease, particularly during a potential second pregnancy. METHODS: Transplantectomy by TLH essentially followed standard TLH procedures. We paid meticulous attention to removing as much donor tissue as possible to prevent postoperative complications from residual donor tissue after stopping IS, as well as long-term vascular damage. RESULTS: TLH was performed successfully without the need to convert to open surgery. Surgical time was 90 min with minimal blood loss. No major complications occurred intra- or postoperatively and during the subsequent 9-month follow-up period. Kidney function normalized. CONCLUSIONS: To our knowledge, we report the first successful TLH-based removal of a uterine allograft in a primipara after LD UTx, thus demonstrating the feasibility of TLH in uterus recipients with MRKHS.

Urinary Tract Tumor Organoids Reveal Eminent Differences in Drug Sensitivities When Compared to 2-Dimensional Culture Systems.

Generation of organoids from urinary tract tumor samples was pioneered a few years ago. We generated organoids from two upper tract urothelial carcinomas and from one bladder cancer sample, and confirmed the expression of cytokeratins as urothelial antigens, vimentin as a mesenchymal marker, and fibroblast growth factor receptor 3 by immunohistochemistry. We investigated the dose response curves of two novel components, venetoclax versus S63845, in comparison to the clinical standard cisplatin in organoids in comparison to the corresponding two-dimensional cultures. Normal urothelial cells and tumor lines RT4 and HT1197 served as controls. We report that upper tract urothelial carcinoma cells and bladder cancer cells in two-dimensional cultures yielded clearly different sensitivities towards venetoclax, S63845, and cisplatin. Two-dimensional cultures were more sensitive at low drug concentrations, while organoids yielded higher drug efficacies at higher doses. In some two-dimensional cell viability experiments, colorimetric assays yielded different IC50 toxicity levels when compared to chemiluminescence assays. Organoids exhibited distinct sensitivities towards cisplatin and to a somewhat lesser extent towards venetoclax or S63845, respectively, and significantly different sensitivities towards the three drugs investigated when compared to the corresponding two-dimensional cultures. We conclude that organoids maintained inter-individual sensitivities towards venetoclax, S63845, and cisplatin. The preclinical models and test systems employed may bias the results of cytotoxicity studies.

CD24: A Marker for an Extended Expansion Potential of Urothelial Cancer Cell Organoids In Vitro?

BACKGROUND: Bladder cancer is the most cost-intensive cancer due to high recurrence rates and long follow-up times. Bladder cancer organoids were considered interesting tools for investigating better methods for the detection and treatment of this cancer. METHODS: Organoids were generated from urothelial carcinoma tissue samples, then expanded and characterized; the expression of immune modulatory antigens and tumor stem cells markers CD24 and CD44 was explored in early (P ≤ 3) and later (P ≥ 5) passages (P) by immunofluorescence and by quantitative PCR of cDNA. The expression of these factors was investigated in the corresponding cancer tissue samples by immunohistochemistry. RESULTS: The expression of the PD-L1 was detected on some but not all organoids. CD276 and CD47 were observed on organoids in all passages investigated. Organoids growing beyond passage 8 expressed both CD24 and CD44 at elevated levels in early and late cultures. Organoids proliferating to the eighth passage initially expressed both CD24 and CD44, but lost CD24 expression over time, while CD44 remained. Organoids growing only up to the 6th passage failed to express CD24 but expressed CD44. CONCLUSIONS: The data indicate that the expression of CD24 in urothelial cancer cell organoids may serve as an indicator for the prolonged proliferation potential of the cells.

Elevated Expression of the Immune Checkpoint Ligand CD276 (B7-H3) in Urothelial Carcinoma Cell Lines Correlates Negatively with the Cell Proliferation.

The cell surface molecule CD276 (B7-H3) is an immune checkpoint antigen. The elevated expression of CD276 on tumors contributes to the suppression of anti-tumor T-cell responses and correlates with poor prognosis. METHODS: The expression of CD276 was explored in vitro on eight urothelial carcinoma cell lines (UM-UC) in comparison to eight normal urothelial cells (NUCs) by RT-qPCR, Western blotting, and flow cytometry. Cell proliferation was enumerated over consecutive passages. The expression of cancer stem cell markers CD24 and CD44, cytokeratins, and vimentin was investigated by immunofluorescence. The expression of CD276 in bladder tumor samples and metastases was explored by immunohistochemistry. RESULTS: Expression of CD276 on cell surfaces was elevated on UM-UCs when compared to NUCs. In UM-UCs, CD276 transcripts correlated moderately positive with CD276 protein expression (ρ = 0.660) and strongly positive with CD276 surface-expression (ρ = 0.810). CD276 mRNA expression (ρ = -0.475) and CD276 protein expression (ρ = -0.417) had a significant negative correlation with proliferation, while a significant correlation between proliferation and cell surface expression was not observed in UM-UCs. CONCLUSION: The expression of CD276 on UM-UC bladder tumor cell surfaces is elevated. Slow proliferating UM-UC cells express more CD276 mRNA and protein than fast proliferating cells. In patients, slow proliferating CD276high tumor (stem) cells may evade immune surveillance. However, cancer therapy targeting CD276 may be effective in the treatment of slow proliferating tumor cells.

Replacing Needle Injection by a Novel Waterjet Technology Grants Improved Muscle Cell Delivery in Target Tissues.

Current regimen to treat patients suffering from stress urinary incontinence often seems not to yield satisfactory improvement or may come with severe side effects. To overcome these hurdles, preclinical studies and clinical feasibility studies explored the potential of cell therapies successfully and raised high hopes for better outcome. However, other studies were rather disappointing. We therefore developed a novel cell injection technology to deliver viable cells in the urethral sphincter complex by waterjet instead of using injection needles. We hypothesized that the risk of tissue injury and loss of cells could be reduced by a needle-free injection technology. Muscle-derived cells were obtained from young male piglets and characterized. Upon expansion and fluorescent labeling, cells were injected into cadaveric tissue samples by either waterjet or injection needle. In other experiments, labeled cells were injected by waterjet in the urethra of living pigs and incubated for up to 7 days of follow-up. The analyses documented that the cells injected by waterjet in vitro were viable and proliferated well. Upon injection in live animals, cells appeared undamaged, showed defined cellular somata with distinct nuclei, and contained intact chromosomal DNA. Most importantly, by in vivo waterjet injections, a significantly wider cell distribution was observed when compared with needle injections (P < .05, n ≥ 12 samples). The success rates of waterjet cell application in living animals were significantly higher (≥95%, n = 24) when compared with needle injections, and the injection depth of cells in the urethra could be adapted to the need by adjusting waterjet pressures. We conclude that the novel waterjet technology injects viable muscle cells in tissues at distinct and predetermined depth depending on the injection pressure employed. After waterjet injection, loss of cells by full penetration or injury of the tissue targeted was reduced significantly in comparison with our previous studies employing needle injections.

Robotic-assisted plate osteosynthesis of the anterior pelvic ring and acetabulum: an anatomical feasibility study.

Pelvic ring injuries or acetabular fractures present a challenge to trauma surgeons. Recently, endoscopic dissection techniques for visualization of the anterior pelvic ring and acetabulum have been presented. Robotic-assisted surgical systems offer advantages in terms of improved visualization and easier instrument handling. The aim of this pilot anatomic study was to verify the feasibility of robotic-assisted plate osteosynthesis on the anterior pelvic ring and acetabulum. The experiment was performed on a human whole body specimen. The DaVinci system with standard instruments as used in RARP was used. After docking the system, the anterior pelvic ring was first prepared as previously described for the endoscopic techniques. This was followed by dissection of both acetabula analogous to pelvic lymphadenectomy as performed during RARP. After the dissection was performed along the pelvic brim up to the iliosacral joint, the complete anterior column of the acetabulum including quadrilateral surface and incisura ischiadica major could be visualized. Finally, robotic-assisted endoscopic plate osteosynthesis was performed on the symphysis and anterior acetabular column as previously described in the endoscopic techniques. Robotic-assisted plate osteosynthesis of the anterior pelvic ring and acetabulum is feasible with the available robotic-assisted systems. Due to the excellent freedom of movement of the robotic arms, combined with the magnifying 3D visualization of the system, highly accurate preparation of the situs in preparation for plate osteosynthesis can be performed. The question of reduction of dislocated fractures remains open and is the subject of further investigation. Compared with conventional laparoscopy, robotic-assisted preparation nevertheless appears to offer an advantage in view of the complexity of the operation.

A retrospective analysis of perioperative complications associated with retropubic tension-free vaginal tape in 960 women.

PURPOSE: The purpose is to analyse perioperative complications associated with the retropubic tension-free vaginal tape (TVT) procedure and their management. METHODS: This retrospective, monocentric cohort study included 960 women after retropubic TVT procedure performed by one surgeon from 2011 to 2016. Complications were identified up to 6 weeks after the procedure, divided into specific and general complications and classified based on the Clavien-Dindo (CD) Classification. A visit 6 weeks after the surgical procedure was attended by all patients. RESULTS: 77 complications, of which 74 occurred postoperatively and 3 intraoperatively, affecting 72 (7.5%) out of 960 women. Urinary retention and voiding problems were the most common complication. The mean age of women suffering complications was 3.4 years higher in comparison to the mean age of women without complications (p = 0.036). The Body Mass Index (BMI) of the group of women with perioperative complications had an average BMI which was 0.5 kg/m2 lower than the average BMI of the women without complications. 22 (12.8%) out of 172 women with recurrent stress incontinence had postoperative complications, of which 21 were related to the TVT. CONCLUSION: The retropubic TVT is a surgical procedure associated with a low number of perioperative complications, even in the group of elderly and overweight women, as well as in cases of recurrent stress incontinence.

Robotic Transrectal Computed Tomographic Ultrasound with Artificial Neural Network Analysis: First Validation and Comparison with MRI-Guided Biopsies and Radical Prostatectomy.

INTRODUCTION: There is still a lack of availability of high-quality multiparametric magnetic resonance imaging (mpMRI) interpreted by experienced uro-radiologists to rule out clinically significant PC (csPC). Consequently, we developed a new imaging method based on computed tomographic ultrasound (US) supported by artificial neural network analysis (ANNA). METHODS: Two hundred and two consecutive patients with visible mpMRI lesions were scanned and recorded by robotic CT-US during mpMRI-TRUS biopsy. Only significant index lesions (ISUP ≥2) verified by whole-mount pathology were retrospectively analyzed. Their visibility was reevaluated by 2 blinded investigators by grayscale US and ANNA. RESULTS: In the cohort, csPC was detected in 105 cases (52%) by mpMRI-TRUS biopsy. Whole-mount histology was available in 44 cases (36%). In this subgroup, mean PSA level was 8.6 ng/mL, mean prostate volume was 33 cm3, and mean tumor volume was 0.5 cm3. Median PI-RADS and ISUP of index lesions were 4 and 3, respectively. Index lesions were visible in grayscale US and ANNA in 25 cases (57%) and 30 cases (68%), respectively. Combining CT-US-ANNA, we detected index lesions in 35 patients (80%). CONCLUSIONS: The first results of multiparametric CT-US-ANNA imaging showed promising detection rates in patients with csPC. US imaging with ANNA has the potential to complement PC diagnosis.