Assessing the Use of BotulinumtoxinA for Hyperactive Urinary Tract Dysfunction a Decade after Approval: A Single-Blind Study to Evaluate the Reduction in Pain in OnabotulinumtoxinA Detrusor Injection Using Different Injection Needles.

Overactive bladder (OAB) has a significant impact on the quality of life; thus, it requires treatment that can be adhered to over a long period without undue side effects. The current treatment which uses an anticholinergic or ß-3 agonist may fail to improve symptoms and has side effects, leading to high discontinuation rates. OnabotulinumtoxinA (OnabotA) detrusor injection has been approved for idiopathic OAB as a second-line treatment with good effectiveness and tolerability. This study used a visual analog scale (VAS) to assess the impact of the type of needle used for OnabotA detrusor injections under local anesthesia on the pain levels after each injection. This study included 68 female patients. We used three different needles with thicknesses ranging from 22 to 27 gauge, lengths between 4 and 5 mm, and different cuts. The sensation of pain was rated at each standardized injection location. Regardless of the needle used, the patients' perceptions of pain at the beginning of the procedure were rated as being less than the subsequent injections. Most pain sensations were rated as low to moderate. The mean pain sensation on the VAS was 2.5 ± 0.3 overall, i.e., for all patients and needles used. Statistically significant differences in pain sensation were rated only at some locations of the bladder (on the back wall and the right side of the bladder). The single needles averaged the following pain scores: 2.8 ± 0.3 for needle A (20 G, 4 mm), 2.1 ± 0.3 for needle B (27 G, 5 mm), and 2.6 ± 0.4 for needle C (20 G, 4 mm, sharp cut 15°). The 27-gauge needle caused significantly less pain, and it had no negative impact due to its length, which was 1 mm longer than the other needles. Thus, the needle thickness was a decisive factor in the patients' perceptions of pain.

CEA (CEACAM5) expression is common in muscle-invasive urothelial carcinoma of the bladder but unrelated to the disease course.

Objectives: Carcinoembryonic antigen (CEA) is a cell surface glycoprotein that represents a promising therapeutic target. Serum measurement of shedded CEA can be utilized for monitoring of cancer patients. Material and Methods: To evaluate the potential clinical significance of CEA expression in urothelial bladder neoplasms, CEA was analysed by immunohistochemistry in more than 2500 urothelial bladder carcinomas in a tissue microarray format. Results: CEA staining was largely absent in normal urothelial cells but was observed in 30.4% of urothelial bladder carcinomas including 406 (16.7%) with weak, 140 (5.8%) with moderate, and 192 (7.9%) with strong staining. CEA positivity occurred in 10.9% of 411 pTaG2 low-grade, 32.0% of 178 pTaG2 high-grade, and 43.0% of 93 pTaG3 tumours (p < 0.0001). In 1335 pT2-4 carcinomas, CEA positivity (34.1%) was lower than in pTaG3 tumours. Within pT2-4 carcinomas, CEA staining was unrelated to pT, pN, grade, L-status, V-status, overall survival, recurrence free survival, and cancer specific survival (p > 0.25). Conclusion: CEA increases markedly with grade progression in pTa tumours, and expression occurs in a significant fraction of pT2-4 urothelial bladder carcinomas. The high rate of CEA positivity in pT2-4 carcinomas offers the opportunity of using CEA serum measurement for monitoring the clinical course of these cancers. Moreover, CEA positive urothelial carcinomas are candidates for a treatment by targeted anti-CEA drugs.

The Feasibility of Practical Training in Minimally Invasive Surgery at Medical School-A Prospective Study on the Pelvitrainer.

Background and Objectives: The acquisition of practical skills at medical school is an important part of the multidimensional education program of future physicians. However, medical schools throughout the world have been slow in incorporating practical skills in their curriculum. Therefore, the aims of the present prospective study were (a) to demonstrate the feasibility of such surgical training, (b) to objectify its benefit in medical education, and (c) to investigate the impact of such training on subsequent career choices. Material and Methods: We introduced a two-day laparoscopy course on the pelvitrainer as part of the curriculum of the gynecological internship of fifth year medical students from 2019 to 2020. The results of the students' training were matched to those of surgeons who completed the same curriculum in a professional postgraduate laparoscopy course from 2017 to 2020 in a comparative study design. Additionally, we performed a questionnaire-based evaluation of the impact of the course on medical education and subsequent career choices directly before and after completing the course. Results: A total of 261 medical students and 206 physicians completed the training program. At baseline, the students performed significantly more poorly than physicians in a median of three of four exercises (p < 0.001). However, this evened out in the final runs, during which students performed more poorly than physicians only in one exercise and even better than physicians in one. The general integration of surgical training in medical school curricula was rated very low (12.4% on the VAS, IQR 3-16%) despite the high demand for such training. In the survey, the course was deemed very beneficial for medical education (median VAS 80.7%, IQR 73-98%), but did not appear to influence the students' subsequent career preferences. Conclusions: The acquisition of practical surgical skills during medical school is significantly under-represented in many medical faculties. The benefits of such training, as demonstrated in our study, would improve the education of future physicians.

The Allium Ureteral Stent for the Treatment of Ureteral Complications Following Renal Transplantation-A Single-Center, Single-Surgeon Series.

Ureteral complications such as urinary leak, ureteral necrosis or ureteral stenosis are common complications after renal transplantation with major short- and long-term issues, including graft impairment and graft loss. At present, there is no agreement on the optimal management of ureteral complications. The aim of the current study was to evaluate the safety and efficacy of the self-expanding, large-caliber Allium ureteral stent in patients with ureteral complications following renal transplantation. In this retrospective study, the electronic database of Charité University Hospital was screened for patients receiving the self-expandable Allium ureteral stent in the transplant ureter after kidney transplantation between January 2016 and March 2022. Descriptive statistics were used to describe the outcomes. There were six men and four women with a median age of 61 years (interquartile range, 55 to 68 years). Nine out of 10 patients had ureteric stenosis, which was diagnosed at a median of two years (interquartile range 10 months to 9 years) following renal transplantation. The median operating time was 49 min (interquartile range, 30 to 60 min). Endoscopic Allium stent placement was successful in all patients with ureteric stenosis. The median length of stay in the hospital was four days (interquartile range 2 to 7 days). Only one patient (#5) had a postoperative grade IIIb Clavien-Dindo complication. Patients had follow-ups every 3 months with ultrasound and serum creatinine. Dislocation of the Allium stent was seen in four patients; all occurred within three months. Ultimately, three patients required ureteric re-implantation, two of which had early dislocation of the stent. Six patients are managed with a permanent Allium stent. The median dwell time was 11 months (interquartile range 3 to 20 months) and maximum dwell time was 23 months. The overall success rate was 60% (6 out of 10). According to our data, the Allium stent represents a safe and minimally invasive option with a success rate of 60%. It might, therefore, represent an alternative to DJ stents, nephrostomies or immediate re-implantation. As all dislocations occurred within three months, frequent early postoperative follow-up is required.

Loss of TROP2 and epithelial cell adhesion molecule expression is linked to grade progression in pTa but unrelated to disease outcome in pT2-4 urothelial bladder carcinomas.

Introduction: Trophoblast cell surface antigen 2 (TROP2; EpCAM2) is a transmembrane glycoprotein which is closely related to EpCAM (EpCAM; EpCAM1). Both proteins share partial overlapping functions in epithelial development and EpCAM expression but have not been comparatively analyzed together in bladder carcinomas. TROP2 constitutes the target for the antibody-drug conjugate Sacituzumab govitecan (SG; TrodelvyTM) which has been approved for treatment of metastatic urothelial carcinoma by the United States Food and Drug administration (FDA) irrespective of its TROP2 expression status. Methods: To evaluate the potential clinical significance of subtle differences in TROP2 and EpCAM expression in urothelial bladder cancer, both proteins were analyzed by multiplex fluorescence immunohistochemistry in combination with a deep-learning based algorithm for automated cell detection on more than 2,700 urothelial bladder carcinomas in a tissue microarray (TMA) format. Results: The staining pattern of TROP2 and EpCAM were highly similar. For both proteins, the staining intensity gradually decreased from pTa G2 low grade (TROP2: 68.8±36.1; EpCAM: 21.5±11.7) to pTa G2 high grade (64.6±38.0; 19.3±12.2) and pTa G3 (52.1±38.7; 16.0±13.0, p<0.001 each). In pT2-4 carcinomas, the average TROP2 and EpCAM staining intensity was intermediate (61.8±40.9; 18.3±12.3). For both proteins, this was significantly lower than in pTa G2 low grade (p<0.001 each) but also higher than in pTa G3 tumors (p=0.022 for TROP2, p=0.071 for EpCAM). Within pT2-4 carcinomas, the TROP2 and EpCAM staining level was unrelated to pT, grade, UICC-category, and overall or tumor-specific patient survival. The ratio TROP2/EpCAM was unrelated to malignant phenotype and patient prognosis. Conclusion: Our data show that TROP2 and EpCAM expression is common and highly interrelated in urothelial neoplasms. Despite of a progressive loss of TROP2/EpCAM during tumor cell dedifferentiation in pTa tumors, the lack of associations with clinicopathological parameters in pT2-4 cancer argues against a major cancer driving role of both proteins for the progression of urothelial neoplasms.

Mode of delivery of women with Swyer syndrome in a German case series.

OBJECTIVES: For women with Swyer Syndrome, a 46,XY gonadal dysgenesis, full term pregnancies are possible after oocyte donation. According to literature, mode of delivery is almost always by Caesarean section for various reasons. Medical indications are multiple pregnancies and related complications, preeclampsia, an androgynous shaped pelvis and failed induction of labor. Elective Caesarean sections were performed based on maternal request and medical recommendation. METHODS: Following careful examination and shared decision making, we planned a spontaneous delivery with a patient with Swyer syndrome and tested the different hypotheses regarding anatomical and functional features according to literature. In addition, deliveries of women with Swyer Syndrome were analyzed in a German multicenter case series. RESULTS: A total of seven women with Swyer syndrome with a total of 10 pregnancies were identified, who later gave birth to twelve live-born children. Seven out of 10 births were performed by elective and non-elective Caesarean section, three births took place vaginally. CONCLUSIONS: In summary, the risk of Caesarean section delivery has increased, but spontaneous delivery can be attempted in the event of inconspicuous findings.

Endovascular and open surgical options in the treatment of uretero-arterial fistulas.

OBJECTIVE: To report and analyze the indications and results of endovascular and open surgical treatment for uretero-arterial fistula. METHODS: We retrospectively reviewed the clinical data of 25 consecutive patients with uretero-arterial fistulas admitted to our hospital from 2011 to 2020. Endpoints were technical success, freedom from open conversion, stent-graft/graft-related complications, and 30-day and one-year mortality. RESULTS: The study included 25 patients (68% female, n = 17) with 27 uretero-arterial fistulas by bilateral pathologies in two patients. The mean age was 61 ± 11 years (range 35-80). The most common predisposing factors for uretero-arterial fistula were history of pelvic operations for malignancy in 21 patients (84%), radiotherapy in 21 patients (84%), previous pelvic vascular bypass in 2 patients (8%), and iliac aneurysms in 2 patients (8%). On average, the period between the primary pelvic surgery and the diagnosis of uretero-arterial fistulas was 46 months (range 7-255). Twenty patients (80%) underwent endovascular treatment of the uretero-arterial fistulas. The primary technical success of the endovascular treatment was 95%, and the freedom from open conversion was 40% at six months and 30% at one year. Thirteen uretero-arterial fistulas (48%) underwent delayed open conversion due to recurrent bleeding in six cases (46%), stent-graft infection in three cases (23%), or pelvic abscess in four cases (31%). Primary open surgery was applied for five (20%) patients. After a mean follow-up of 34 months, early (<30 days) mortality was 8% (2/25), one-year mortality 16% (4/25), and overall mortality was 24% (6/25). CONCLUSIONS: Uretero-arterial fistula is a late complication of prior pelvic surgery, radiation, and indwelling ureteral stents. Endovascular treatment remains an effective and less invasive modality in controlling the related life-threatening arterial bleeding of the uretero-arterial fistula. Open surgical treatment is still required for patients with local sepsis, previously failed endovascular treatment or infected stent-grafts.

Nerve Sparing Radical Hysterectomy: Short-Term Oncologic, Surgical, and Functional Outcomes.

There is an obvious prevalence of disparity in opinions concerning the technique of nerve-sparing radical hysterectomy and its application, despite agreement on the need to spare the pelvic autonomic nerve system during such a radical operation. Understanding the precise three-dimensional anatomy of paracolpium and its close anatomical relationship to the components of the pelvic autonomic nervous system is the key in performing the nerve-sparing radical hysterectomy. A total of 42 consecutive patients with primary cervical cancers, who were operated upon in our institution between January 2017 and June 2019, were analyzed, concerning surgical, urinary functional, and short-term oncologic outcomes. Two thirds of the patients had locally advanced tumors (T > 40 mm or pT ≥ IIA2) with a median tumor size of 44.1 mm. The nerve-sparing radical hysterectomy was combined with the complete recovery of bladder function in 90% of patients directly after surgery and in 97% of patients in the first 2 weeks. The recurrence rate in a median follow-up time of 18 months was 9.5%. The nerve-sparing radical hysterectomy approach, which depends on the comprehensive understanding of the precise entire anatomy of paracolpium, was found to be feasible and applicable, even in locally advanced tumors, with good functional results and convincing short-term oncologic outcomes.

Iatrogenic endometriosis following apical pelvic organ prolapse surgery: a case report.

BACKGROUND: Iatrogenic endometriosis is the presence of endometrial glands and stroma out of the uterus following certain surgical interventions. The rate of iatrogenic endometriosis after gynecologic surgeries due to benign uterine disease is 1-2%. Laparoscopic supracervical hysterectomy is also a part of frequently used surgical treatment of apical pelvic organ prolapse, which is followed by sacrocervicopexy. However, there are no data about iatrogenic endometriosis after apical prolapse surgery in the current literature. Herein, we present a case report of a patient diagnosed with de novo endometriosis 1 year after laparoscopic supracervical hysterectomy and sacrocervicopexy. CASE PRESENTATION: A 46-year-old parous Slavic woman who underwent laparoscopic supracervical hysterectomy and sacrocervicopexy secondary to grade 3 symptomatic apical prolapse 1 year earlier was admitted to the same clinic with pelvic pain that had started 6 months following surgery. Deep vaginal palpation was painful. Transvaginal ultrasonography revealed an area with hypervascularization on the sacral promontory. She was scheduled for diagnostic laparoscopy. A 2 × 2-cm solid, wine-colored, hypervascular hemorrhagic lesion was seen on the sacral promontory. The lesion and the peritoneal layer behind it were totally excised. The patient was discharged on the first postoperative day, without any complications. Pathologic examination revealed foci of endometriosis comprising endometrial glands and stroma within the connective tissue, along with hemosiderin-laden macrophages. The symptoms of the patient resolved after the surgery, and no further adjuvant treatment was needed. CONCLUSION: Although the rate of iatrogenic endometriosis is low after laparoscopic supracervical hysterectomy and sacrocervicopexy, the possibility of the occurrence of iatrogenic endometriosis should be discussed with patients who are diagnosed with apical prolapse to determine the type of surgical intervention. Iatrogenic endometriosis should be kept in mind for differential diagnosis in case of pain after laparoscopic supracervical hysterectomy and sacrocervicopexy.

The addition of a sagittal image fusion improves the prostate cancer detection in a sensor-based MRI /ultrasound fusion guided targeted biopsy.

BACKGROUND: To explore the diagnostic benefit of an additional image fusion of the sagittal plane in addition to the standard axial image fusion, using a sensor-based MRI/US fusion platform. METHODS: During July 2013 and September 2015, 251 patients with at least one suspicious lesion on mpMRI (rated by PI-RADS) were included into the analysis. All patients underwent MRI/US targeted biopsy (TB) in combination with a 10 core systematic prostate biopsy (SB). All biopsies were performed on a sensor-based fusion system. Group A included 162 men who received TB by an axial MRI/US image fusion. Group B comprised 89 men in whom the TB was performed with an additional sagittal image fusion. RESULTS: The median age in group A was 67 years (IQR 61-72) and in group B 68 years (IQR 60-71). The median PSA level in group A was 8.10 ng/ml (IQR 6.05-14) and in group B 8.59 ng/ml (IQR 5.65-12.32). In group A the proportion of patients with a suspicious digital rectal examination (DRE) (14 vs. 29%, p = 0.007) and the proportion of primary biopsies (33 vs 46%, p = 0.046) were significantly lower. The rate of PI-RADS 3 lesions were overrepresented in group A compared to group B (19 vs. 9%; p = 0.044). Classified according to PI-RADS 3, 4 and 5, the detection rates of TB were 42, 48, 75% in group A and 25, 74, 90% in group B. The rate of PCa with a Gleason score ≥7 missed by TB was 33% (18 cases) in group A and 9% (5 cases) in group B; p-value 0.072. An explorative multivariate binary logistic regression analysis revealed that PI-RADS, a suspicious DRE and performing an additional sagittal image fusion were significant predictors for PCa detection in TB. 9 PCa were only detected by TB with sagittal fusion (sTB) and sTB identified 10 additional clinically significant PCa (Gleason ≥7). CONCLUSION: Performing an additional sagittal image fusion besides the standard axial fusion appears to improve the accuracy of the sensor-based MRI/US fusion platform.

The detection of significant prostate cancer is correlated with the Prostate Imaging Reporting and Data System (PI-RADS) in MRI/transrectal ultrasound fusion biopsy.

PURPOSE: To evaluate the performance of real-time MRI/ultrasound (MRI/US) fusion-guided targeted biopsy (TB) in men with primary and repeat biopsies and correlate the prostate cancer detection rate (CDR) with the PI-RADS score. METHODS: Analysis included 408 consecutive men with primary and prior negative biopsies who underwent TB and 10-core random biopsy (RB) between January 2012 and January 2015. TB was performed with a real-time MRI/US fusion platform with sensor-based registration. Clinically significant PCa was defined as Gleason score (GS) ≥ 7 or GS 6 with maximal cancer core length ≥ 4 mm for TB and according to Epstein criteria for RB. RESULTS: The overall CDR was 56 % (227/408). The CDR for primary biopsy was 74 % (60/81) and 57 % (67/117), 49 % (62/126), 45 % (38/84) for patients with 1, 2 and ≥ 3 prior negative biopsies. CDRs correlated with PI-RADS 2/3/4/5 were 16 % (5/32), 26 % (29/113), 62 % (94/152) and 89 % (99/111), respectively. The rates of significant tumors in relation to PI-RADS 2/3/4/5 were 60 % (3/5), 66 % (19/29), 74 % (70/94), 95 % (94/99). In 139 (61 %) cases with radical prostatectomy (RP), the rates of ≥ pT3 tumors in correlation with PI-RADS 4 and 5 were 20 % (11/56) and 49 % (32/65). PI-RADS constituted the strongest predictor of significant PCa detection (p < 0.007). CONCLUSIONS: Real-time MRI/US fusion-guided TB combined with RB improved PCa detection in patients with primary and repeat biopsies. The CDR was strongly correlated with a rising PI-RADS score, values of 4 and 5 increasing the detection of clinically significant tumors and leading to a higher histological stage after RP.

Novel low-cost prostate resection trainer-description and preliminary evaluation.

BACKGROUND: Transurethral resection of the prostate (TURP) is a challenging operation for residents with limited endoscopic experience. A number of virtual TURP simulators have been validated in the past. This study is the first description and preliminary evaluation of a non-virtual, low-cost TURP trainer as a teaching tool for residents in urology. METHODS: Dr K. Forke's prostatic resection trainer (PRT; LS 10-2/S, Samed GmbH, Dresden, Germany) was tested during the surgical training of a resident. Under the supervision of an experienced senior surgeon, three aspects were examined: the resection trainer's approximation to reality, the ease of instruction, and the potential capability to improve surgeons' psychomotor abilities with regard to the three-dimensional (3D) guidance of the instrument. The improvement in resection speed (RS) of residents with no PRT training (control group) was also compared to the results of the PRT-trained resident. RESULTS: During the PRT training, the resident displayed clear improvement in resection quality (RQ) and a 27% increase in RS (p = 0.03). In the post-training stage, the PRT-trained resident showed a more constant progress rate, to a maximum RS of 0.37 g/min (35% increase; p = 0.01), whereas the control group displayed varied RS learning curves. Composed of a synthetic material, which can be resected by standard instruments, the trainer offers a haptical experience that is particularly realistic and may provide an increased learning rate. CONCLUSION: From the findings, we conclude that this novel PRT is suitable for daily use and offers an effective and more affordable alternative to virtual simulators. Further validation studies will follow and new fields of application will be tested.

MRI morphology of the levator ani muscle, endopelvic fascia, and urethra in women with stress urinary incontinence.

OBJECTIVE: To evaluate pathomorphologic changes of the levator ani muscle, endopelvic fascia, and urethra in women with stress urinary incontinence (SUI) by MRI. STUDY DESIGN: Fifty-four women with SUI were examined by MRI (1.5T): body phased-array coil, axial and coronal proton-density-weighted sequences. RESULTS: The urethral sphincter muscle showed a reduced thickness of its posterior portion (37%), an omega shape (13%) or higher signal intensity (50%); its abnormal configuration was associated with an increased signal intensity in 70% (p=0.001). The levator ani muscle comprised an unilateral loss of substance in 30%, a higher signal intensity in 28%, and altered origin in 19%. Central defects of the endopelvic fascia were present in 39% (n=21), lateral defects in 46%. There was a significant association between loss of the symphyseal concavity of the anterior vaginal wall and lateral fascial defects (p=0.001) and levator ani changes (p=0.016). CONCLUSION: MRI yields findings supporting current theories on the pathogenesis of SUI.