A preliminary study on a new model system to evaluate tumour-detection and tumour-purging protocols in ovarian cortex tissue intended for fertility preservation.

STUDY QUESTION: Is it possible to create a model system that mimics ovarian metastatic disease in order to devise new strategies to detect cancer cells and prevent cancer cell transmission via ovarian tissue autotransplantation in cancer survivors? SUMMARY ANSWER: Injection of bovine or human ovarian cortex fragments with cells from different cancer types led to the formation of proliferating tumour masses and newly formed small metastatic lesions. WHAT IS KNOWN ALREADY: Autotransplantation of ovarian tissue comes with the major concern of cancer cells possibly being present in the tissue. A model system to develop strategies aimed at enhancing the safety of ovarian tissue autotransplantation is currently lacking. STUDY DESIGN, SIZE, DURATION: The ability of injected human leukaemia, lymphoma, Ewing's sarcoma or breast cancer cells to proliferate and form tumour-like structures in bovine and human ovarian cortex tissue in vitro was assessed. The injected cells were from human cancer cell lines. After 4 days of culture, some tissue fragments were harvested for standard histological staining and immunohistochemical staining of tumour cell specific antigens and the Ki67 proliferation marker, while the remaining fragments were incubated for an additional 6 days (bovine tissue) or 3 days (human tissue) before analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Experiments were performed with ovarian tissue from women after prophylactic salpingo-oophorectomy. Bovine ovarian tissue was obtained at an abattoir. Glucose uptake during in vitro culture was monitored to quantify the viability of tissue. Tumour formation was assessed at Day 4 and Day 10 in bovine ovarian tissue and at Day 4 and Day 7 in human ovarian tissue, using histology and immunohistochemistry. MAIN RESULTS AND THE ROLE OF CHANCE: We found that bovine and human ovarian cortex tissue could be cultured for up to 10 and 7 days, respectively, without any loss of viability. Our preliminary results show that all cell lines tested were capable of forming proliferating tumours in ovarian cortex tissue in vitro. Lymphoma and breast cancer cells produced small metastases near the original lesions. LIMITATIONS, REASONS FOR CAUTION: The tumour model presented was based on the growth of human cancer cell lines in ovarian cortex tissue. It is unknown whether these cells behave differently from malignant cells derived from primary tumours. In addition, the human ovarian tissue was derived from women over 39 years of age, which is obviously considerably older than patients opting for ovarian tissue cryopreservation. WIDER IMPLICATIONS OF THE FINDINGS: Our model system will facilitate the development of procedures to detect cancer cells in, or purge cancer cells from, human ovarian tissue. STUDY FUNDING/COMPETING INTERESTS: Unconditional funding was received from the Radboud Institute for Health Sciences, KiKa Foundation and Merck Serono. There are no conflicts of interest to declare.

Efficacy of ovarian tissue cryopreservation in a major European center.

PURPOSE: To evaluate the effect of cryopreservation and thawing of ovarian tissue from oncological patients opting for fertility preservation on ovarian tissue viability. METHODS: In this prospective cohort study, the ovarian tissue viability before and after cryopreservation and thawing was measured for 25 newly diagnosed oncological patients who had their ovarian tissue cryopreserved. Outcome measures were follicle integrity (histology), follicle viability (Calcein viability assay), steroid hormone production (estradiol and progesterone production in vitro) and overall tissue viability (glucose uptake in vitro). This study was conducted at a Cryobank for storage of ovarian tissue in a university hospital. RESULTS: Cryopreserved/thawed ovarian tissue showed a decreased glucose uptake when compared to tissue that had not been cryopreserved. In addition, a diminished E2 and P4 production was observed after cryopreservation and thawing, despite the fact that numbers of viable follicles as determined by the Calcein viability assay were comparable. Histological examination revealed a higher percentage of degenerated follicles after cryopreservation and thawing. CONCLUSIONS: Ovarian tissue cryopreservation and thawing impairs the viability of ovarian tissue in oncological patients opting for fertility preservation.

[Implementation of the new collective agreement in 2021 in urological clinics : Expectations and reality]. / Umsetzung des neuen Tarifvertrags ab 2021 in urologischen Kliniken : Wunsch und Wirklichkeit.

The amendment to the collective agreement is intended to significantly improve the working conditions of physicians and includes longer-term duty scheduling, work on a maximum of two weekends per month, less overtime. Smaller hospitals often have problems implementing these requirements and have to make compromises. At least the overtime is now better paid-overall, an improvement in working conditions can only be achieved by increasing the number of staff, then better and more intensive training is also possible.

[Liability for chronic working time violations in medicine: when does the risk of fines and imprisonment loom?] / Haftung für chronische Arbeitszeitverstöße in der Medizin ­ wann drohen Bußgelder und Freiheitsstrafen?

Against the background of the changes in the collective bargaining agreement-for municipal hospitals in the version of January 1, 2021, and for university hospitals in the version of March 7, 2020-this article deals with the legal consequences of chronic violations of the German Working Hours Act in medicine, but especially in surgical specialties such as urology. It includes an overview of current law and sanctions for violations and highlights responsibilities as well as exceptions. It is important to clarify the distribution of responsibilities with regard to working hours in the institution concerned in order to avoid fines and, in the worst case, imprisonment. It should also be clear who is liable in specific cases for persistent working time violations. When changing duty models, it is important to bear in mind that this can lead to a considerable deterioration in the opportunities for further training and education of physicians, meaning that in the long term the compatibility of further training in line with working hours can only be achieved with sufficient staffing of the hospitals. In some cases, this is diametrically opposed to economic interests in the health care system and thus presents an almost insoluble dilemma. In the view of the working group, structural changes in the diagnosis-related group (DRG)-based inpatient sector are needed in the near future.

[Transurethral resection of bladder tumors (TURBT)]. / Transurethrale Resektion von Blasentumoren (TUR-B).

Transurethral resection of bladder tumors (TURBT) is the standard of care for the diagnostics and primary treatment of bladder tumors. These are removed by fragmentation using loop diathermy. The resection area is coagulated for hemostasis. An important aspect is always a complete resection with an adequate amount of detrusor muscle in the specimen. Postoperative intravesical instillation of single-shot chemotherapy has been proven to reduce recurrence rates. Methods for improved tumor visualization (particularly photodynamic diagnostics) are used to enhance tumor detection rates particularly in multifocal tumors or carcinoma in situ (CIS). Thus, recurrence and progression rates can be reduced. Depending on the histological examination of the TURBT specimen, follow-up treatment for non-muscle invasive bladder tumors are adjuvant instillation treatment using chemotherapy or Bacillus Calmette-Guérin (BCG), second look TURBT and early cystectomy or for muscle invasive bladder tumors, radical cystectomy or (oncologically subordinate) trimodal treatment with renewed TURBT, radiotherapy and chemotherapy are indicated. Possible complications of TURBT include bleeding with bladder tamponade, extraperitoneal or intraperitoneal bladder perforation and infections of the urogenital tract.

[Safety and efficacy of en bloc vs. conventional transurethral resection of bladder tumors: a meta-analysis and systematic review]. / Sicherheit und Effizienz der en bloc vs. konventionellen transurethralen Resektion von Blasentumoren: eine Metaanalyse und systematic Review.

BACKGROUND: En bloc tumor resection of bladder tumors (ERBT) is a novel alternative procedure to conventional resection of bladder tumor (cTURBT), which might help to address common problems of the standard method, such as inadequate detrusor muscle in specimens, high re-resection rates and high recurrence rates. OBJECTIVE: To analyze current data on ERBT in efficacy and safety compared to cTURBT. DATA SOURCES: PubMed. STUDY SELECTION: Two independent authors identified trials based on keywords and inclusion criteria. A third author was consulted in case of discrepancies. Screening keywords: ERBT, en bloc transurethral resection of bladder tumor, TURBT en bloc. A meta-analysis of 13 studies was performed. The effect size was estimated based on odds ratios and mean differences including their corresponding two-sided 95% confidence intervals. DATA SYNTHESIS: The analyzed studies comprised a homogenous collective in terms of tumor size, tumor multiplicity and tumor stage. Operation time did not significantly differ between the methods. Differences were observed in hospitalization and catheterization time in favor of ERBT. Reported complications did not show clear differences. There was significantly more detrusor muscle in the specimens in the ERBT group. No significant differences were found in recurrence up to 2 years of follow-up. CONCLUSION: ERBT is a safe alternative to conventional TURBT with promising features regarding effective resection of detrusor muscle. More standardized data on recurrence rates, different resection modalities and resection margin results are needed.

Glucose/lactate metabolism of cryopreserved intact bovine ovaries as a novel quantitative marker to assess tissue cryodamage.

For some patients, the autotransplantation of a cryopreserved-thawed intact ovary might be the best option to preserve their reproductive potential after fertility-threatening treatment. The best procedure to successfully cryopreserve a human ovary without inflicting a devastating level of cryodamage is to date unknown. To optimize this procedure, this study developed an assay to monitor the extent of cryodamage inflicted on bovine ovarian tissue by different cryopreservation protocols. The assay measures glucose and lactate metabolism of ovarian tissue fragments in vitro and determines the extent of cryodamage in cryopreserved ovaries. This study tested the cryoprotective effect of two different routes of administration of the cryoprotectant dimethylsulphoxide (DMSO). The cryoprotective effect was assessed in different tissue layers of the ovary, namely the cortex, the subcortex and the medulla. Submersion of intact ovaries in DMSO prior to freezing-thawing resulted in the complete protection of the glucose/lactate metabolism of the cortex, but not of the inner ovarian mass. Perfusion without simultaneous submersion, resulted in partial protection of cortex, subcortex and medulla, while the combination of submersion and perfusion conveyed the highest level of protection for all three ovarian tissue layers.

[Exacerbation of working conditions due to the economic pressures of hospitals : Mandatory staffing ratios for physicians?] / Verschärfung der Arbeitsbedingungen durch Kostendruck der Krankenhäuser : Verpflichtende Personalschlüssel für Ärzte?

BACKGROUND: In current hospital-based urological care, economic pressure and its influence on urological working and further training conditions are a main point of criticism among young urologists. Against the background of a growing need for young talent in our specialist discipline, there is an urgent need for action. With the introduction of the lower limits for nursing staff, there is now a threat of a reduction in the number of physicians with the aim of reducing costs for business reasons. OBJECTIVE: A mandatory staffing ratio is often mentioned to counteract the downsizing in German clinics. The role of the lower staffing limit is explained in the following article. MATERIALS AND METHODS: We have analyzed the current draft laws of the federal government, as well as position papers and statements from federal political representatives such as the Marburger Bund, Bundesverband Deutscher Urologen and the German Medical Association (Bundesärztekammer) since 2018. RESULTS AND CONCLUSION: The analysis of current developments in nursing policy shows that the first step is a needs-based assessment of personnel and subsequent financing in the clinic setting. With adequate staffing, as in the traffic light scheme of the German Medical Association, not only would clinics position themselves as attractive employers and training centers for large parts of the urological medical profession, but would also significantly improve working conditions, patient care and patient safety. Medical training must remain an essential part of everyday hospital life.

In vitro 17ß-oestradiol release as a marker for follicular survival in cryopreserved intact bovine ovaries.

Transplantation of cryopreserved intact ovaries from cancer patients is a technically challenging option for restoring fertility after sterilizing cancer therapy. In this paper we describe an assay based on 17ß-oestradiol (oestradiol) production, to monitor the functional damage sustained by the ovarian tissue during the freeze/thawing procedure. To this end, fresh bovine ovarian cortical biopsies were cultured in vitro for 7 days. As a control, the oestradiol release of biopsies that had sustained maximal cryodamage was analyzed. In addition the oestradiol release by cortical biopsies from two ME2SO perfused and cryopreserved intact ovaries was analyzed. Oestradiol production could be measured in culture supernatants, while oestradiol release of maximal cryo-damaged biopsies was at background levels. In vitro oestradiol release by cortical biopsies can be used as a functional marker for cryo-damage and indicates that our assay is suitable to optimize the cryopreservation procedure of intact ovaries.

[Analysis of European concepts for specialization training in urology with special consideration of intersectoral further education]. / Analyse von europäischen Weiterbildungskonzepten zum Facharzt für Urologie unter besonderer Berücksichtigung der intersektoralen Weiterbildung.

BACKGROUND: The aim of the study is to compare the German specialization training in urology with other European concepts, to analyze regional differences and to evaluate the development of the personnel structure in urology in German hospitals and private practices for the last 5 years. In addition, possibilities for financial funding of residents in the outpatient sector will be analyzed. MATERIALS AND METHODS: After analyzing the changes in the new Urology Specialization Training Regulations (Musterweiterbildungsordnung), the current urology training situation in Germany was evaluated in a European comparison. A trend analysis of the personnel structure in urology has been performed for recent years. Additionally, a possible intersectoral rotation concept was developed. Financial funding possibilities for urological residents were evaluated in a standardized telephone survey. RESULTS: Compared to other European countries, the exceptional position of German urology with its enormous spectrum becomes evident. In some states, there are already possibilities of financial support provided by regional Associations of Statutory Health Insurance Physicians (Krankenversicherung) for the training of urological residents in private practices. CONCLUSIONS: While the organization of specialization training is commonly nation based in other European countries, there is heterogeneity in Germany due to the sovereignty of the states. Due to the shift of many specialization training contents towards the outpatient sector, alliances between clinics and practices in the sense of intersectoral training will become more important in the future. Therefore, the use of already existing funds and-as a long-term objective-a nationwide access to such funding is desirable.

Eruption prediction aided by electronic tiltmeter data at mount st. Helens.

Telemetry from electronic tiltmeters in the crater at Mount St. Helens contributed to accurate predictions of all six effusive eruptions from June 1981 to August 1982. Tilting of the crater floor began several weeks before each eruption, accelerated sharply for several days, and then abruptly changed direction a few minutes to days before extrusion began. Each episode of uplift was caused by the intrusion of magma into the lava dome from a shallow source, causing the dome to inflate and eventually rupture. Release of magma pressure and increased surface loading by magma added to the dome combined to cause subsidence just prior to extrusion.

The Drift of Saturn's North Polar Spot Observed by the Hubble Space Telescope.

Polar projections of 50 images of Saturn at 889 nanometers and 25 images at 718 nanometers taken by the Hubble Space Telescope in November 1990, as well as 3 images at each wavelength taken in June 1991, have been examined. Among them, 31 show the north polar spot, which is associated with Saturn's polar hexagon, in locations suitable for measurement. In each image, planetocentric coordinates of the polar spot were determined, and the movement of the spot with respect to Saturn's system III rotation rate was studied. During the period of observation, the polar spot had first a short-term westward movement and then a long-term eastward drift. The rate of the long-term drift was -0.060 +/- 0.008 degrees per day with respect to system III, approximately 50 percent greater than previously determined from Voyager. The original 1980 and 1981 Voyager data were combined with the new Hubble images to form an 11-year base line. The eastward drift over the longer period was -0.0569 degrees per day. The long-term drift could be due to uncertainty in the standard value of the internal rotation period, which is 810.7939 +/- 0.148 degrees per 24-hour day. The short-term movement in November 1990 has a rate that is greater in magnitude but opposite in sign and probably represents a real, transient motion of the spot relative to the internal rotation system.

Infrared images of jupiter at 5-micrometer wavelength during the voyager 1 encounter.

A coordinated program to observe Jupiter at high spatial resolution in the 5-micrometer wavelength region was undertaken to support Voyager 1 imaging and infrared radiation experiment targeting. Jupiter was observed over a 5-month period from Palomar and Mauna Kea observatories. The frequency of observations allowed the selection of interesting areas for closer Voyager examination and also provided good short-term monitoring of variations in cloud morphology. Significant global changes in the 5-micrometer distribution are seen over this time period.

Toxicity testing of human assisted reproduction devices using the mouse embryo assay.

Systems to assess the toxicity of materials used in human assisted reproduction currently lack efficiency and/or sufficient discriminatory power. The development of 1-cell CBA/B6 F1 hybrid mouse embryos to blastocysts, expressed as blastocyst rate (BR), is used to measure toxicity. The embryos were divided into control and test groups, and were exposed to either control medium or to a potentially toxic test medium. Inferences on toxicity were based on differences in BR between the two groups. The mouse embryo assay followed a stratified (mouse), randomized (embryo), and balanced (equal number of embryos per group and per mouse) design. The number of embryos needed was calculated using power analysis. The basal BR of the hybrid strain was determined in a historical population. Sixty-nine mouse embryos per group were required to detect toxic materials with sufficient sensitivity and to account for the considerable inter-mouse variation in blastocyst development. Fifty-two samples, divided over batches of seven different products were tested before use in the study IVF centre and five of these were found to be toxic. This test system, presented as the Nijmegen mouse embryo assay (NMEA), can be used to detect embryo-toxic materials in daily IVF practice, and this report may provide a starting point for standardization.

[Workload, job satisfaction, Work Time Act-what is urology doing?] / Arbeitsbelastung, Arbeitszufriedenheit, Arbeitszeitgesetz ­ was macht die Urologie?

Due to demographic changes, the proportion of people requiring urological treatment will continue to rise. In order to better address this development, we need a well-trained and motivated urological medical community. Not only is continued education in urology an integral part of this, but it must also be embedded into future-oriented, flexible work-hour models, taking into account the German Work Time Act. Thus, in order to obtain a better assessment of the current situation of urological physicians undergoing specialist training, work -hour models currently used in urological clinics must be evaluated. This should allow conclusions to be drawn to find future-oriented solutions in order to do justice to the Future Offensive-Urology in 2025. Transparency, openness, and cooperation should be top priority between the DGU (German Association for Urology) working groups active in this field and the working groups of the BvDU (German Professional Association for Urologists).

[Quality instead of quantity improves medical education]. / Qualität statt Quantität verbessert die Weiterbildung.

Currently, continuing medical evaluation takes place in Germany-but not nationally or regularly, and without national standards. Therefore, comparisons between different clinics and trainers can currently not be drawn. Survey modes, such as those that have existed in Switzerland for decades, could provide a constructive basis in the assessment of the current continuing medical education of urology residents and subsequently facilitate the discussion on improvements. This requires constructive cooperation of all involved, without attributing the responsibility only to the educators. Models of rewarding good continuing education should also be found.

[The working time load of specialists and senior physicians in German urology-a critical assessment]. / Die Arbeitszeitbelastung von Fach- und Oberärzten in der deutschen Urologie ­ eine Bestandsaufnahme.

BACKGROUND: The working and continued training conditions of assistant physicians in urology in Germany have already been analyzed. But what about senior urologists in Germany? Under which conditions do they have to work? As far as we know no published data currently exist which illuminate the conditions of this special urological professional group, therefore, the results of this survey are presented. OBJECTIVE: To survey and evaluate the current working conditions of certified and senior urologists in Germany as comprehensively as possible. MATERIAL AND METHODS: The working group of employed physicians of the Professional Association of German Urologists (BvDU) carried out a survey within the framework of the urological senior physician forum 2016 and on-line via the e­mail distributor of the German Society for Urology (DGU). The questions involved the workload, working conditions and satisfaction, overtime performed, working hours and opt out regulations. RESULTS: A total of 176 senior physicians participated in the survey of which 88% were male and 12% female. In Germany there are 1125 senior physicians. The average age of the responders was 44.9 years. In more than 80% of the participants the average weekly working hours were over 50 h and 70% signed an opt out regulation. An association between an increasing job dissatisfaction above a working week over 55 h and an average attendance in on-call service over 4 h could be established. The number of on-call services had no influence on job satisfaction. A total of 43% (70 out of 162) of the participants stated that overtime hours were regularly forfeited and 12% (20 out of 162) that all overtime hours were forfeited. Approximately 30% of senior physicians in German urology were dissatisfied with the current working conditions in the present form. CONCLUSION: Based on the acquired data, adaptation and improvements in the working conditions of senior urologists are necessary in order to maintain the attractiveness of the occupational image and leading positions in German urology.

[Urological infections and antibiotic management in geriatric patients]. / Urologische Infektionen und Antibiotikamanagement bei geriatrischen Patienten.

Both the demographic shift and progress in medicine are resulting in an increasingly longer life expectancy. It is presumed that a mean age of 90 years will be achieved within the next decade in many countries. Thus, geriatric medicine, which is committed to the specific needs of older, often frail and frequently comorbid patients, is becoming increasingly more important. The prevalence of infections of the genitourinary tract increases with age, simultaneously, a critical and conscious use of antibiotics is required in terms of antimicrobial treatment. The intention of the present review is to make the reader aware of the specific characteristics of urinary tract infections and asymptomatic bacteriuria in the older patient population in terms of epidemiology, spectrum of pathogens and resistance as well as the indications for and performance of antimicrobial treatment.

Optimal perfusion of an intact ovary as a prerequisite for successful ovarian cryopreservation.

BACKGROUND: Cryopreservation and subsequent reimplantation of intact ovaries from cancer patients, offers potentially the best prognosis for restoring fertility after sterilizing cancer treatment. We used bovine ovaries as a model system to explore the perfusion procedure that is required for cryopreservation of intact ovaries. METHODS: The arteria ovarica was cannuled, and ovaries were flushed with Indian ink for 5 min. RESULTS: Successful perfusion of blood vessels was immediately visible macroscopically by a grey to black discoloration of the ovary and was confirmed microscopically, by examining tissue sections. There was no correlation between the time interval from removal of the ovary to the start of the perfusion, and success of perfusion. We determined the percentage of Indian ink-perfused vessels and scored blood vessels in four different size classes. The percentage of perfused vessels increased with an increase in vessel size. In a limited set of preliminary experiments with human ovaries, comparable results were obtained. CONCLUSIONS: Our results show that bovine ovaries are a suitable and adequate model system for optimizing the cryopreservation of human ovaries. As bovine are at least of comparable size to human ovaries, we expect that our results can be extrapolated to the human situation.

[Extracorporeal shock wave lithotripsy]. / Extrakorporale Stoßwellenlithotripsie.

Interventional treatment of stones essentially consists of three treatment modalities. Extracorporeal shockwave lithotripsy (ESWL), in addition to uterorenoscopy (URS) and percutaneous nephrolitholapaxy (PCNL) is an essential treatment pillar and is the only noninvasive therapy option for the treatment of urinary stones. After a long period of ESWL being the leading choice in stone treatment, the number of SWL interventions diminished in recent years in favor of the other two treatment modalities (URS and PCNL). This article describes the indications, surgical technique and management of complications of SWL.