Residents and patients benefit from surgical simulation on a live porcine model, could we consider it as ethical?

INTRODUCTION: The objective was to evaluate, by self-questionnaire, the feeling of participants in surgical training sessions on a live porcine model. METHODS: A computerized questionnaire (GoogleForm ©) was sent to the members of the French Association of Urologists-in-Training (AFUF) (fellows and residents). Only questionnaires from Urologists-in-training who had participated in surgical training sessions were included. The sessions consisted of performing surgeries such as laparoscopic nephrectomies or laparoscopic cystectomies. RESULTS: Overall, 198 met the inclusion criteria. A total of 36.4% (72/198) of the participants were fellows and 63.6% (126/198) were residents. According to the participants, the main interest of sessions was to be able to train for emergency situations. A total of 79.8% (158/198) of the participants wanted surgical simulation to become compulsory. To their opinion, the main advantage of surgical simulation on a live porcine model was: technical progress in 87.4% (173/198) of cases. A total of 13.1% (26/198) of the participants found it was unethical to perform the first technical procedures on live animal models. A total of 65.7% (130/198) of the participants considered that there is currently no system of substitution. CONCLUSION: For the participants, surgical training on a live porcine model allows technical progress while training for serious emergency situations. Surgeons and patients could benefit from this risk-free mock surgical scenario. LEVEL OF EVIDENCE: 3.

Educational program in onco-urology for young urologists: What are their needs?

PURPOSE: The emergence of new communication media such as digital contents are progressively replacing more traditional medias in the field of educational programs. Our purpose was to assess urologist in training aspirations regarding urological education. METHODS: Members of a national urologist in training association were sent an anonymous online questionnaire regarding their medical formation in the field of urology. Responders interest for urological sub-specialty or education support (new tools and traditional support) were evaluated through a 5-point Likert scale. RESULTS: Overall, 109 young urologists (26%) responded to the survey. Most of the respondents worked during their training in an academic hospital (n=89, 82%). The three favorite tools for training chosen by the responders were: videos, workshop or masterclass, and podcasts (responders very interested were respectively n=64 (58.7%), n=50 (45.9%), and n=49 (45%)). E-mail newsletters were reported as the less useful educational tool by participants (n=38, 34.9%). Participants were very interested in improving their surgical skills and their radiological knowledge. Responders who were the most attracted by PCa were much more looking to improve their systemic treatment and radiological knowledges. CONCLUSIONS: Urologic-oncology was a priority regarding education for urologists in training. A majority of participants expressed a lack in their surgical education, revealing a reduced OR access and underlining utilization of new tools such as simulation. New digital contents such as social media or podcast achieved high interest for the participants, instead of more traditional media. There is a need that educational content evolve and uses new digital media. LEVEL OF EVIDENCE: 3.

COVID19 pandemic impacts on anxiety of French urologist in training: Outcomes from a national survey.

INTRODUCTION: The COVID-19 outbreak in France is disturbing our health system. Urologists in training who are already known to have burnout, are in the front line to face this disease. The aim of our study was to assess the psychological impact of COVID-19 pandemic on young French urologists in training. MATERIAL AND METHODS: A self-administered anonymous questionnaire evaluating the pandemic added stress, and its negative impact on work and training quality, was e-mailed to the members of the French Association of Urologists in Training (AFUF). The association includes all French junior and senior residents. The survey lasted 3 days. Multivariable analyses using logistic regression was performed to identify the predictive factors. RESULTS: Two hundred and seventy-five (55.5%) of the 495 AFUF members responded to the questionnaire. More than 90% of responders felt more stressed by the pandemic. Fellows and senior residents were more likely to feel that the crisis had an important impact on their work quality (OR=1.76, IC95=[1.01-3.13]), even more when COVID 19 patients were present in their department (OR=2.31, IC95=[1.20-4.65]). Past medical history of respiratory disease (OR=2.57, IC95=[1.31-5.98]) and taking in charge COVID19 patients (OR=1.85, IC95=[0.98-3.59]) were additional risk factors. CONCLUSION: COVID19 pandemic has a negative impact on young French urologists in training and on their work and training quality. Managing their psychosocial well-being during this time is as important as managing their physical health. LEVEL OF EVIDENCE: 3.

[Venous thromboembolism and urological cancer: Epidemiology and therapeutically management]. / Maladie thromboembolique veineuse et cancers urologiques : épidémiologie et prise en charge thérapeutique.

INTRODUCTION: Active cancer is a risk factor in the occurrence of venous thromboembolism (VTE). This is the second cause of death for these patients. In onco-urology, some cancers are associated with an increased risk of VTE. The aim of this study was to propose a focus of epidemiology and VTE therapy management. MATERIAL AND METHODS: A systematic analysis of the PubMed® database was performed through the PRISMA methodology using the followings keywords : "neoplasm", "venous thromboembolism", "prophylaxis", "pulmonary embolism", "urology". The original papers were included with a priority on: meta-analyzes, literature reviews, randomized controlled trials and good-level proof cohort studies. Only publications in English or French have been selected. RESULTS: The incidence of VTE was more important in case of renal carcinomas (3.5%/year). When surgery was proposed cystectomy was the riskiest procedure (2.6 to 11.6% VTE). Chemotherapy alone was an important risk factor increasing by a factor of six the occurrence of VTE. Hormonotherapy also increased this risk by induced hypogonadism. The curative treatment for VTE associated with cancers has to be performed through the injection of low molecular weight heparin. The implantation of a prophylactic treatment was not systematic among patients diagnosed with urological cancer. CONCLUSION: The understanding of mechanisms associated with the occurrence of VTE among these patients has enabled to improve patient management, especially those suffering from urological cancer. Undeniably, frequency of VTE is probably underestimated by urologists during clinical practice.

Isolated continent cystostomy on neurologic native bladder: Functional results.

INTRODUCTION: Continent cutaneous urinary diversion (CCUD) is proposed to patients suffering from chronic neurologic retention and undergoing intermittent self-catheterization (ISC). In case of neurogenic detrusor overactivity (NDO), augmentation enterocystoplasty is often required. The aim was to identify the prevalence of urinary stomal and/or urethral leakage in patients who had not undergone enlargement. METHODS: Monocentric, retrospective study of patients who underwent CCUD surgery in a neuro-urological context. Mitrofanoff's, Monti's or Casale's channels were performed. Patients selected had an underactive, stable, or stabilized bladder under adjuvant therapy with proper cystomanometric capacity. Prior or concomitant enterocystoplasty were excluded. Failure was defined as the occurrence of clinical leakage whatever it is through urinary stomal, or urethral. Urodynamic parameters were also reported. RESULTS: Thirty-one patients underwent surgery. Nine women had a concomitant bladder neck sling and 1 urethral closure. The mean follow-up was 7 years. 8/31 (26%) had stomal leakage and 9 urethral leakage (29%). Five spinal cord injured patients (n=14) had stomal leakage (36%) and 6 urethral leakage (43%). Of the 25 postoperative urodynamic parameters, cystomanometric bladder capacity was 419mL (vs. 514mL) and 2 additional patients had de novo NDO (9 vs. 7). DISCUSSION: The morbidity of augmentation enterocystoplasty is weighed against the presence of a well-controlled bladder preoperatively. Our study shows the appearance of leakage in some patients despite a well-balanced bladder, a decrease in mean cystomanometric capacity and an increase in the rate of NDO postoperatively. Good selection criteria for an isolated CCUD should be carefully revised and defined. LEVEL OF EVIDENCE: Grade C - retrospective study.

Generation of coherent 19- and 38-nm radiation at a free-electron laser directly seeded at 38 nm.

Initiating the gain process in a free-electron laser (FEL) from an external highly coherent source of radiation is a promising way to improve the pulse properties such as temporal coherence and synchronization performance in time-resolved pump-probe experiments at FEL facilities, but this so-called "seeding" suffers from the lack of adequate sources at short wavelengths. We report on the first successful seeding at a wavelength as short as 38.2 nm, resulting in GW-level, coherent FEL radiation pulses at this wavelength as well as significant second harmonic emission at 19.1 nm. The external seed pulses are about 1 order of magnitude shorter compared to previous experiments allowing an ultimate time resolution for the investigation of dynamic processes enabling breakthroughs in ultrafast science with FELs. The seeding pulse is the 21st harmonic of an 800-nm, 15-fs (rms) laser pulse generated in an argon medium. Methods for finding the overlap of seed pulses with electron bunches in spatial, longitudinal, and spectral dimensions are discussed and results are presented. The experiment was conducted at FLASH, the FEL user facility at DESY in Hamburg, Germany.

Electron bunch timing with femtosecond precision in a superconducting free-electron laser.

High-gain free-electron lasers (FELs) are capable of generating femtosecond x-ray pulses with peak brilliances many orders of magnitude higher than at other existing x-ray sources. In order to fully exploit the opportunities offered by these femtosecond light pulses in time-resolved experiments, an unprecedented synchronization accuracy is required. In this Letter, we distributed the pulse train of a mode-locked fiber laser with femtosecond stability to different locations in the linear accelerator of the soft x-ray FEL FLASH. A novel electro-optic detection scheme was applied to measure the electron bunch arrival time with an as yet unrivaled precision of 6 fs (rms). With two beam-based feedback systems we succeeded in stabilizing both the arrival time and the electron bunch compression process within two magnetic chicanes, yielding a significant reduction of the FEL pulse energy jitter.

Compact single-shot electro-optic detection system for THz pulses with femtosecond time resolution at MHz repetition rates.

Electro-optical detection has proven to be a valuable technique to study temporal profiles of THz pulses with pulse durations down to femtoseconds. As the Coulomb field around a relativistic electron bunch resembles the current profile, electro-optical detection can be exploited for non-invasive bunch length measurements at accelerators. We have developed a very compact and robust electro-optical detection system based on spectral decoding for single-shot longitudinal bunch profile monitoring at the European X-ray Free Electron Laser (XFEL) for electron bunch lengths down to 200 fs (rms). Apart from the GaP crystal and the corresponding laser optics at the electron beamline, all components are housed in 19 in. chassis for rack mount and remote operation inside the accelerator tunnel. An advanced laser synchronization scheme based on radio-frequency down-conversion has been developed for locking a custom-made Yb-fiber laser to the radio-frequency of the European XFEL accelerator. In order to cope with the high bunch repetition rate of the superconducting accelerator, a novel linear array detector has been employed for spectral measurements of the Yb-fiber laser pulses at frame rates of up to 2.26 MHz. In this paper, we describe all sub-systems of the electro-optical detection system as well as the measurement procedure in detail and discuss the first measurement results of longitudinal bunch profiles of around 400 fs (rms) with an arrival-time jitter of 35 fs (rms).

Long-term stable microwave signal extraction from mode-locked lasers.

Long-term synchronization between two 10.225 GHz microwave signals at +10 dBm power level, locked to a 44.26 MHz repetition rate passively mode-locked fiber laser, is demonstrated using balanced optical-microwave phase detectors. The out-of-loop measurement result shows 12.8 fs relative timing jitter integrated from 10 Hz to 10 MHz. Long-term timing drift measurement shows 48 fs maximum deviation over one hour, mainly limited by drift of the out-of-loop characterization setup itself. To the best of our knowledge, this is the first time to demonstrate long-term (>1 hour) 3 mrad-level phase stability of a 10.225 GHz microwave signal extracted from a mode-locked laser.

Amplification of the c-myc oncogene during progression of radiation-induced rat skin tumors.

Evaluation of a large panel of radiation-induced rat skin tumors of diverse size and histological type revealed a correlation between c-myc copy number and tumor size. Both the frequency and degree of c-myc gene amplification were increased in large compared to small carcinomas, but none of the sarcomas examined showed c-myc amplification. Serial biopsies of individual tumors exhibited similar trends of increasing c-myc copy number in later biopsies. In one regressing tumor, the c-myc gene copy number paralleled the growth rate of the tumor during growth and regression. The average time required from tumor appearance to significant gene amplification was close to the average period between tumor appearance and the onset of rapid growth. The data suggest that, rather than being a target gene for the direct early effects of ionizing radiation, c-myc functions as a late-stage progression-related oncogene in this model system.

Towards (99m)Tc-based imaging agents with effective doxorubicin mimetics: a molecular and cellular study.

Doxorubicin is a clinical benchmark drug, which is applied in the treatment of numerous cancers. Known for its accumulation in the nucleus and ability to intercalate into DNA, it targets quickly dividing i.e. hypermitotic cells. Through this mechanism, it could be an ideal structural motif for a new class of imaging agents, given that the new entity approximates the in vitro profile of the parent drug. Here we describe design, synthesis and biological activity of a small array of Doxorubicin-metalloconjugates (M = (99m)Tc, Re). We demonstrate that the conjugates preferably accumulate in the nuclear compartment, tightly bind to DNA and retain an appreciable cytotoxicity. Moreover, the Re conjugates effectively act as inhibitors of the human Topoisomerase II enzyme, which is the widely accepted mechanism of action of the parent drug. Since the conjugates effectively mimic the in vitro behavior of native Doxorubicin, the (99m)Tc compounds are prospective imaging agents.

Her-2/neu and urokinase-type plasminogen activator and its inhibitor in breast cancer.

PURPOSE: Recent studies suggest that HER-2/neu specifically promotes the invasive capacity of tumor cells by up-regulating secretion of the proteolytic enzyme, urokinase-type plasminogen activator (uPA), or its inhibitor, plasminogen activator inhibitor-1 (PAI-1), in colon and gastric cancer. It was the purpose of this study to: (a) evaluate the association between HER-2/neu and uPA and PAI-1 expression in a large primary breast cancer cohort; (b) perform the first multivariate analysis, including HER-2/neu, uPA, and PAI-1 in breast cancer; and (c) define the effect of HER-2/neu overexpression on uPA and PAI-1 expression in breast cancer cells. EXPERIMENTAL DESIGN: HER-2/neu, uPA, and PAI-1 were measured as continuous variables by ELISA in primary breast cancer tissue extracts from 587 patients with clinical follow-up and analyzed for correlations with clinical outcome. Furthermore, a full-length human HER-2/neu cDNA was introduced into five human breast cancer cell lines to define the effects of HER-2/neu overexpression on uPA and PAI-1 expression. In addition, we tested whether HER-2/neu antibodies could reverse any given alteration of uPA and PAI-1 levels. RESULTS: Our findings indicate a weak positive association between HER-2/neu and uPA (r = 0.147; P < 0.001) and no association between HER-2/neu and PAI-1 (r = 0.07; P = 0.085). HER-2/neu overexpression (> or =400 fmol/mg) and high levels of uPA/PAI-1 (> or =5.5 ng/mg and/or > or =14 ng/mg, respectively) were significantly associated with shorter disease-free survival (DFS; P < 0.001 and P = 0.003) and metastasis-free survival (MFS; P = 0.015 and P < 0.001). Multivariate analysis revealed prognostic independence between HER-2/neu and the uPA/PAI-1 axis for DFS and MFS. Both uPA and PAI-1 had no significant discriminatory effect among HER-2/neu-positive patients for DFS. The prognostic value of HER-2/neu overexpression for MFS, however, was significantly enhanced by elevated uPA expression (P = 0.053). Stable transfection of the HER-2/neu gene into multiple human breast cancer cell lines resulted in consistent down-regulation of uPA or PAI-1 expression. In addition, anti-HER-2/neu antibodies did not significantly affect uPA or PAI-1 expression in human cancer cell lines naturally overexpressing HER-2/neu. CONCLUSIONS: The present findings suggest that the invasive phenotype elicited by HER-2/neu overexpression in breast cancer is not a direct effect of uPA or PAI-1 expression. HER-2/neu and the uPA/PAI-1 axis have been shown to affect the invasive capacity of breast cancer independently. Determination of uPA can provide significant additional prognostic information for MFS in HER-2/neu-positive and -negative patients.

(99m)Tc radiolabelling of Fe3O4-Au core-shell and Au-Fe3O4 dumbbell-like nanoparticles.

The development of nanoparticle-based dual-modality probes for magnetic resonance imaging (MRI) and positron emission tomography (PET) or single photon emission computed tomography (SPECT) is increasingly growing in importance. One of the most commonly used radionuclides for clinical SPECT imaging is (99m)Tc and the labelling of Fe3O4 nanoparticles with (99m)Tc was shown to be a successful strategy to obtain dual-modality imaging agents. In this work, we focus on gold containing magnetic nanomaterials. The radiolabelling of magnetic Fe3O4-Au core-shell and Fe3O4-Au dumbbell-like nanoparticles with the [(99m)Tc(CO)3](+) fragment is described. The key elements for this (99m)Tc labelling approach are novel coating ligands, consisting of an anchor for the Au surface, a polyethylene glycol linker and a strong chelator for the [(99m)Tc(CO)3](+) moiety.

Femtosecond all-optical synchronization of an X-ray free-electron laser.

Many advanced applications of X-ray free-electron lasers require pulse durations and time resolutions of only a few femtoseconds. To generate these pulses and to apply them in time-resolved experiments, synchronization techniques that can simultaneously lock all independent components, including all accelerator modules and all external optical lasers, to better than the delivered free-electron laser pulse duration, are needed. Here we achieve all-optical synchronization at the soft X-ray free-electron laser FLASH and demonstrate facility-wide timing to better than 30 fs r.m.s. for 90 fs X-ray photon pulses. Crucially, our analysis indicates that the performance of this optical synchronization is limited primarily by the free-electron laser pulse duration, and should naturally scale to the sub-10 femtosecond level with shorter X-ray pulses.

Amplification of the c-myc oncogene in radiation-induced rat skin tumors as a function of linear energy transfer and dose.

The c-myc oncogene was previously shown to be amplified in large, later-stage carcinomas of the rat skin induced by 0.8-MeV electrons. In a panel of 70 tumors induced by neon ions (45 keV/microns), c-myc amplification was rare, and in contrast to the data for tumors induced by low-linear-energy transfer (LET) (0.3 keV/microns) radiation, showed no correlation with tumor size, growth period, or time, but was associated with radiation dose. The tissue specificity for c-myc amplification seen in tumors induced by electrons was not seen in tumors induced by neon ions. These results suggest that quite distinct molecular mechanisms operate even in late stages of carcinogenesis that depend on the LET of the inducing radiation. Furthermore, the results suggest that c-myc amplification observed in tumors induced by low-LET radiation is not a general property of rat skin carcinomas, but is linked mechanistically to the inducing radiation, even though it is not detectable until many months after exposure and tumor appearance.

Rare activation of ras oncogenes in radiation induced rat skin tumors.

We examined a large panel of radiation induced rat skin tumors for activation of the H- or K-ras oncogenes. Using oligonucleotide hybridization analysis of tumor DNA we found that only 1 out of 96 tumors tested had an activated K-ras gene, and none of the 78 tumors examined for H-ras mutations were positive. Tumors were induced by high and low LET, and included lesions of various sizes and histologic type. DNA sequencing of tumors and NIH3T3 transfectants from a previous study gave results consistent with a rare occurence of ras activation in this system.

[Diagram for the prognosis of cephalo-pelvic disproportions. Application in 300 cases of pelvic contraction]. / Diagramme pour le pronostic des disproportions céphalo-pelviennes. Application à 300 observations de rétrécissements pelviens

The authors using the information obtained by X-ray pelvimetry and ultrasound cephalometry in 300 cases of contracted pelves, suggest a diagram of cephalo-pelvic disproportion that can be used in the great majority of cases of contracted pelves. It is not applicable to those where there is significant deformation of the middle strait or an abnormality of presentation. It is divided into three zones: 1. A superior zone, favourable, into which the majority (60%) of cases of contracted pelvis fit. The risk of a serious dystocia during delivery is so small (less than 2%) that it can be considered scarcely different from those found in women with a normal pelvis. 2. An intermediate zone into which 24% of cases of contracted pelvis fit where the prognosis is uncertain. The labour should be considered as an "at risk" labour and a trial of labour conducted. 3. A lower zone into which 16% of the cases fit and which consists of two categories: --those in which the biparietal diameter is equal to or less than 90 mm. Prophylactic caesarean section should be avoided in these cases where disproportion is rare and where there is a risk of delivering a premature infant: and --those more numerous (9 out of 10) where the biparietal diameter is more than 90 mm and where, unless there is a clinically definitely favourable prognosis, it is justifiable to carry out prophylactic caesarean section. If this line is followed: one can avoid a large number of trials of labour, all of which are inconvenient and some of which are dangerous for the child; few unnecessary caesarean sections are carried out.

[Spinal metastasis from ovarian granulosa cell tumor--after 23 years]. / Granulosasejtes ováriumtumor spinális metastasisa--23 év után.

On admission, the 63-year-old patient suffered from spinal chord compression at the level of D. IV. vertebra. 23 years earlier she had undergone a total uterus exstirpation for ovarian tumor, with bilateral adnexectomy. The microcellular granular cell tumor potentially regarded as malignant, gave a spinal metastasis after 23 years of "dormancy". Half a year after the second spinal surgery, the growth again reached compression-size, requiring reoperation. On discussing the case, the authors also deal with the clinical signs of ovarian tumors as well as their prognosis and treatment modalities.

Circadian variation of rectal sensitivity and gastrointestinal peptides in healthy volunteers.

The aim of our study was to identify diurnal variation of perception of rectal distension and the release of gastroenteropancreatic hormones. In 12 healthy male volunteers (25 years, range 22-32), a rectal balloon distension was performed. Rectal perception thresholds (minimal, urge and pain) and rectal compliance were double-measured with a computer-controlled barostat at seven standardized time points during the day (from 16.00 to 14.00 hours the following day). Blood samples were taken 30 min before and after each rectal distension procedure to determine plasma levels of cholecystokinin (CCK), pancreatic polypeptide (PP) and motilin. Sensory thresholds for urge and pain varied significantly with the time of day, with higher threshold levels in the evening than in the morning hours. Bowel wall compliance showed as well-significant variance at pain threshold and was higher during daytime than in the evening or at night. In contrast to motilin, release of CCK and PP also showed a significant variation depending on daytime. Perception of rectal distension stimuli as well as compliance was independent of intake of food and peptide hormone levels, but CCK and PP levels increased with food, and PP levels decreased with rectal distension. Significant differences in the perception of rectal distension stimuli for urge and pain depending on daytime were found, but the release of gastrointestinal peptides seemed not to be involved. This circadian variation needs to be taken into account in patients and volunteer studies.

DNA fingerprinting analysis of radiation-induced rat skin tumors.

DNA fingerprinting analysis was performed on rat skin tumors induced by high linear energy transfer neon ion radiation. Most of these tumors (13/15) showed DNA-fingerprint variability between independently isolated tumors from the same animal. These changes include multiple band shifts and extra bands. Comparisons of DNA fingerprints were also made on successive biopsy samples from the same tumor. Each of 3 neon-induced tumors and 2 of 8 electron (low LET) induced tumors showed progressive loss of amplified sequences, gain of amplified sequences, deletions, band shifts, and the appearance of extra bands in progressive biopsies. These results provide evidence for LET-specific effects on genomic instability in radiation-induced rat skin tumors.