New concepts of reconstructive techniques with human amniotic membrane in pelvic floor surgery

1. SUMMARY Due to the aging of society and the growing number of oncology cases, there is a need for new and efficient reconstruction techniques in urology. Native tissue is often not available or can be in bad condition after multimodal treatments with surgery and radio-chemotherapy. Various methods and materials have been developed to date to replace the damaged tissues. The possible indications embrace the partial or complete replacement of the ureter, bladder or urethra, repair of complex fistulas and protection of anastomoses. One of the strongest tissues in the human body and one with multiple growth factors, human amniotic membrane (HAM) could serve as a potential graft in reconstructive urology. Amniotic tissue can be easily harvested during Caesarean sections and is therefore broadly available. However, by now its application is limited to cornea replacement and burn therapy. Therefore, our first aim was to develop a manufacturer-independent, standardized in vitro process for the preparation of amnion grafts. In this line, we planned to develop a sterilization and storage technique for frozen and dried HAM with a preserved extracellular matrix. As a next step, we employed an in vivo xenologous model to test previously constructed multilayer HAM grafts and to investigate the capacity to repair small defects in the rat bladder and intestinal tract. HAM provided a durable graft with good functional and histological results for bladder grafting. The initial inflammatory reaction decreased, with no signs of degradation observed over six weeks of follow-up and only subtle signs of graft rejection detected. However, HAM was not suitable for intestinal reconstruction due to an increased rate of adhesions. Next, by following the steps in the Innovation, Development, Exploration, Assessment and Long-term Study for Devices (IDEAL-D) system of surgical innovation, we defined possible human indications. The first-inhuman stage of innovation involved clinical cases of complex fistulas, a vesico-vaginal fistula and a chronic wound with an entero-cutaneous fistula, which were treated successfully with HAM allografts. Based on the promising clinical data, further directions could be planned, targeting ureteral reconstruction or the protection of urethra anastomoses

UBC®Rapid Test for detection of carcinoma in situ for bladder cancer

UBC®Rapid Test is a test that detects fragments of cytokeratins 8 and 18 in urine. We present results of a multicentre study measuring UBC®Rapid Test in bladder cancer patients and healthy controls with focus on carcinoma in situ (CIS) and high-grade bladder cancer. From our study with N = 452 patients, we made a stratified sub-analysis for carcinoma in situ of the urinary bladder. Clinical urine samples were used from 87 patients with tumours of the urinary bladder (23 carcinoma in situ, 23 non-muscle-invasive low-grade tumours, 21 non-muscle-invasive high-grade tumours and 20 muscle-invasive high-grade tumours) and from 22 healthy controls. The cut-off value was defined at 10.0 µg/L. Urine samples were analysed by the UBC®Rapid Test point-of-care system (concile Omega 100 POC reader). Pathological levels of UBC Rapid Test in urine are higher in patients with bladder cancer in comparison to the control group (p < 0.001). Sensitivity was calculated at 86.9% for carcinoma in situ, 30.4% for non-muscle-invasive low-grade bladder cancer, 71.4% for nonmuscle-invasive high grade bladder cancer and 60% for muscle-invasive high-grade bladder cancer, and specificity was 90.9%. The area under the curve of the quantitative UBC®Rapid Test using the optimal threshold obtained by receiveroperated curve analysis was 0.75. Pathological values of UBC®Rapid Test in urine are higher in patients with high-grade bladder cancer in comparison to low-grade tumours and the healthy control group. UBC®Rapid Test has potential to be more sensitive and specific urinary protein biomarker for accurate detection of high-grade patients and could be added especially in the diagnostics for carcinoma in situ and non-muscle-invasive high-grade tumours of urinary bladder cancer

Thermoelectric properties of high quality nanostructured Ge:Mn thin films

We report on the elaboration of germanium manganese nanostructured thin films and the measurement of their thermoelectric properties. We investigate the growth of Ge:Mn layers along with a thorough structural characterization of this materials at the nanoscale. The room temperature thermoelectric properties of these layers containing spherical inclusions are discussed regarding their potential as a model of "electron crystal phonon glass material". We show that the thermal conductivity can be decreased by a factor of 30, even if the electronic properties can be conserved as in the bulk. The thermoelectric performance ZT of such material is as high as 0.15 making them a promising thermoelectric p-type material for Ge related application

Federal Regulation

Introduction Infected wounds are difficult to treat and there are no standardized protocols. Presentation of case We report a case of infected postoperative wound and entero-cutaneous fistula in a 83 years-old woman. An innovative treatment protocol for Human amniotic membrane (HAM)-assisted dressing of infected wound as the Idea Stage following the IDEAL recommendations is presented. The development of amnion preparation and the involved treatment steps are described. No adverse events and no graft rejection have been detected. Discussion Favorable results confirm the technical simplicity, safety and efficacy of this procedure. HAM has been shown to promote wound healing and to have antibacterial characteristics, which was supported by the presented case. Conclusion We are able to report a successful treatment of an infected wound caused by entero-cutaneous fistula with HAM dressing. Following the IDEAL recommendations, consecutive prospective cohort trials are justified

Safety and Outcome of Modified Laparoscopic Bilateral Sacropexy

Sacropexy is a generally applied treatment of prolapse, yet there are known possible complications of it. An essential need exists for better alloplastic materials. Methods. Between April 2013 and June 2014, we performed a modified laparoscopic bilateral sacropexy (MLBS) in 10 patients using a MRI-visible PVDF mesh implant. Selected patients had prolapse POP-Q stages II-III and concomitant OAB. We studied surgery-related morbidity, anatomical and functional outcome, and mesh-visibility in MRI. Mean follow-up was 7.4 months. Results. Concomitant colporrhaphy was conducted in 1/10 patients. Anatomical success was defined as POP-Q stage 0-I. Apical success rate was 100% and remained stable. A recurrent cystocele was seen in 1/10 patients during follow-up without need for intervention. Out of 6 (6/10) patients with preoperative SUI, 5/6 were healed and 1/6 persisted. De-novo SUI was seen in 1/10 patients. Complications requiring a relaparoscopy were seen in 2/10 patients. 8/10 patients with OAB were relieved postoperatively. The first in- human magnetic resonance visualization of a prolapse mesh implant was performed and showed good quality of visualization. Conclusion. MLBS is a feasible and safe procedure with favorable anatomical and functional outcome and good concomitant healing rates of SUI and OAB. Prospective data and larger samples are required

Protocol for a Randomized Phase II Trial for Mesh Optimization by Autologous Plasma Coating in Prolapse Repair: IDEAL Stage 3

Introduction: Mesh-related complications especially after vaginal implantation have raised awareness lately because of severe adverse reactions and legal aspects. About 20% of patients suffer from complications after mesh insertion in the anterior vaginal wall. Autologous plasma coating of meshes prior to implantation has shown potential to improve the biocompatibility of meshes in vivo and in vitro. This innovative approach has been developed according to the IDEAL recommendations for surgical innovations. The method has still to be assessed at stage 3 accordingly. Methods: A protocol is developed for a prospective single-blinded randomized controlled phase II trial for biocompatibility optimization of anterior vaginal meshes for prolapse repair by autologous plasma coating versus non-coated meshes. Results: The protocol aims at fulfilling the requirements for stage 3 (assessment) according to IDEAL. Eligible for inclusion are women with primary cystocele, requiring a surgical procedure, suitable for randomization, and willing to be randomized. Participants will be followed up by postal questionnaires (6 months post surgery and 12 months post randomization) and will also be reviewed in clinic 12 and 24 months post surgery. Primary endpoint is the assessment of mesh-related complications following the Clavien–Dindo classifications. QoL, sexual function assessment, efficacy, and validation of an already developed long-term register are considered secondary endpoints. To afford a calculated 10% reduction of postoperative complications through plasma-coated meshes vs. non-coated meshes at 1-year follow-up, a total 214 women in each arm will be necessary to achieve 80% power at a significance level of 5%. Conclusion: The protocol for this randomized clinical trial represents the conditions to assess the surgical innovation of plasma coating of meshes in order to improve the meshes’ biocompatibility at stage 3 according to the IDEAL recommendations. © 2017 Springer Healthcar

Nomograms including the UBC® Rapid test to detect primary bladder cancer based on a multicentre dataset

Objectives: To evaluate the clinical utility of the urinary bladder cancer antigen test UBC Rapid for the diagnosis of bladder cancer (BC) and to develop and validate nomograms to identify patients at high risk of primary BC. Patients and Methods: Data from 1787 patients from 13 participating centres, who were tested between 2012 and 2020, including 763 patients with BC, were analysed. Urine samples were analysed with the UBC Rapid test. The nomograms were developed using data from 320 patients and externally validated using data from 274 patients. The diagnostic accuracy of the UBC Rapid test was evaluated using receiver-operating characteristic curve analysis. Brier scores and calibration curves were chosen for the validation. Biopsy-proven BC was predicted using multivariate logistic regression. Results: The sensitivity, specificity, and area under the curve for the UBC Rapid test were 46.4%, 75.5% and 0.61 (95% confidence interval [CI] 0.58–0.64) for low-grade (LG) BC, and 70.5%, 75.5% and 0.73 (95% CI 0.70–0.76) for high-grade (HG) BC, respectively. Age, UBC Rapid test results, smoking status and haematuria were identified as independent predictors of primary BC. After external validation, nomograms based on these predictors resulted in areas under the curve of 0.79 (95% CI 0.72–0.87) and 0.95 (95% CI: 0.92–0.98) for predicting LG-BC and HG-BC, respectively, showing excellent calibration associated with a higher net benefit than the UBC Rapid test alone for low and medium risk levels in decision curve analysis. The R Shiny app allows the results to be explored interactively and can be accessed at www.blucab-index.net. Conclusion: The UBC Rapid test alone has limited clinical utility for predicting the presence of BC. However, its combined use with BC risk factors including age, smoking status and haematuria provides a fast, highly accurate and non-invasive tool for screening patients for primary LG-BC and especially primary HG-BC

Functional Recovery after the Application of Amniotic Tissues and Methylene Blue during Radical Prostatectomy—A Pilot Study

Amniotic tissues and methylene blue (MB) provide the ability for neuroregeneration, and MB enables intraoperative neurostaining. We first combined the techniques to explore a neuroprotective effect on early functional outcomes in a retrospective proof-of-concept trial of 14 patients undergoing radical prostatectomy (RP). The patients were followed up at a median of 13 months, and the continence and potency rates were reported. Early recovery of continence was found after three months. No effect on potency was detected. The findings indicate the feasibility of this tissue-engineering strategy, and justify prospective comparative studies

Prostatic sarcoma of the Ewing family in a 33-year-old male – A case report and review of the literature

Ewing sarcoma is the second most common primary bone tumor seen in children and adolescents, typically presenting between 10 and 20 years of age. Extraosseous sarcomas of the Ewing family in adults are rare. We report a manifestation of this tumor entity in the periprostatic tissue of a 33-year-old male and discuss our treatment approach. Transrectal biopsy is a feasible and simple diagnostic tool for unclear pelvic masses. Multi-modal therapy and central registries are needed to gain knowledge of rare pelvic tumors like Ewing sarcoma. Keywords: Ewing sarcoma, Pelvic neoplasms, Adult, Surgery, Chemotherapy, Prostat