The NeuroSAFE frozen section technique during radical prostatectomy - Implementation and optimization of technical aspects in a routine pathology workflow.

BACKGROUND AND AIMS: In prostate cancer patients, application of the NeuroSAFE frozen section technique during radical prostatectomy has been shown to increase the rate of nerve sparing surgery and to improve functional outcome for the patients. The aim of this study is to report on technical and organizational optimization opportunities of the procedure. MATERIAL AND METHODS: All patients submitted to bilateral intraoperative frozen section from January 2018 until December 2020 (n = 452) were retrospectively analyzed and parameters such as turnaround time, staff situation in the laboratory and histologic properties of the tumors were assessed. RESULTS: The median turnaround time per case was 40.3 ( ± 10.5) min. In 2020 the average time needed from accessioning to diagnosis was 38.1 min. Multivariate linear regression suggested that the number of technical assistants/cryotomes (46.1 min vs. 39.13 min; p < 0.001), the place of microscopic examination (43.0 min vs. 38.7 min; p < 0.001) and the presence of a positive margin (38.0 vs. 44.0 min; p < 0.001) were significant influential factors. The turnaround time was independent of the uropathological expertize of the consultant (39.84 min vs. 40.7 min; p = 0.09), the tumor grade (42.3 vs 39.8 min; p = 0.493) and the presence of extraprostatic extension (44.0 vs 39.8 min; p = 0.099). CONCLUSION: The implementation of simple optimization measures in the workflow as well as structured training of all pathology staff involved in the examination leads to a significant increase in the efficiency of the examination while maintaining the same level of resources. The results could thus be a contribution to the broader application of the procedure.

Trial Participation is Not Associated with Better Biochemical Recurrence-free Survival in a Large Cohort of External Beam Radiotherapy-Treated Intermediate- and High-Risk Prostate Cancer Patients.

AIMS: There is a widespread belief that outcomes of cancer patients treated within clinical trials might not be representative of the outcomes obtained within standard clinical settings. We sought to investigate the effect of trial participation on biochemical recurrence (BCR) in localised, D'Amico intermediate- and high-risk prostate cancer patients treated with external beam radiotherapy (EBRT). MATERIALS AND METHODS: We relied on a study population treated with EBRT between January 2001 and January 2021 at a single tertiary care centre, stratified according to trial enrolment. Separate Kaplan-Meier and multivariable Cox regression models tested BCR-free survival at 60 months within intermediate- and high-risk EBRT patients, after adjustment for covariables. Additionally, the analyses were refitted after inverse probability treatment weighting was performed separately for both risk subgroups. RESULTS: Of 932 eligible patients, 635 (68%) and 297 (32%) had intermediate- and high-risk prostate cancer, respectively. Overall, 53% of patients were trial participants. BCR rates were 11 versus 5% (P = 0.27) and 12 versus 14% (P = 0.08) in trial participants versus non-participants for intermediate- and high-risk subgroups, respectively. Differences in patient and clinical characteristics were recorded. Trial participation status failed to reach predictor status in multivariable Cox regression models for BCR in both intermediate-risk (hazard ratio 1.34; 95% confidence interval 0.71-2.49; P = 0.4) and high-risk patients (hazard ratio 1.03; 95% confidence interval 0.45-2.34; P = 0.9). Virtually the same results were recorded in inverse probability treatment weighting cohorts. CONCLUSIONS: Relying on a large cohort of EBRT-treated intermediate- and high-risk patients, no BCR differences were recorded between trial participants and non-participants after accounting for confounders.

Learning curve and functional outcomes after laser enucleation of the prostate for benign prostate hyperplasia according to surgeon's caseload.

PURPOSE: To evaluate the impact of surgical caseload on safety, efficacy, and functional outcomes of laser enucleation of the prostate (LEP) applying a structured mentoring program. METHODS: Patient characteristics, perioperative data, and functional outcomes were analyzed descriptively. Linear and logistic regression models analyzed the effect of caseload on complications, functional outcomes and operative speed. Within the structured mentoring program a senior surgeon was present for the first 24 procedures completely, for partial steps in procedures 25-49, and as needed thereafter. RESULTS: A total of 677 patients from our prospective institutional database (2017-2022) were included for analysis. Of these, 84 (12%), 75 (11%), 82 (12%), 106 (16%), and 330 patients (49%) were operated by surgeons at (A) < 25, (B) 25-49, (C) 50-99, (D) 100-199, and (E) ≥ 200 procedures. Preoperative characteristics were balanced (all p > 0.05) except for prostate volume, which increased with caseload. There was no significant difference in change of IPSS, Quality of life, ICIQ, pad usage, peak urine flow, residual urine, and major complications (Group A: 8.3 to E: 7.6%, p = 0.2) depending on the caseload. Caseload was not associated (Odds ratio: 0.7-1.4, p > 0.2) with major complications in the multivariable logistic regression model. Only operating time was significantly shorter with increasing caseload in the multivariable analysis (111-55 min, beta 23.9-62.9, p < 0.001). CONCLUSION: With a structured mentoring program, the safety and efficacy of LEP can be ensured even during the learning curve with very good outcome quality. Only the operating time decreases significantly with increasing experience of the surgeon.

[Movember health care initiative 2019: prostate cancer screening at the University Hospital Frankfurt]. / Urologische Prostatakrebsvorsorge im Rahmen der Movember-Gesundheitsinitiative 2019 am Universitätsklinikum Frankfurt.

BACKGROUND: Men die earlier than women in Germany. Men also have impaired access to cancer screening compared to women. OBJECTIVES: Our Movember campaign 2019 at University Hospital Frankfurt (UKF) aimed at improving health care awareness in the context of prostate cancer checkup. MATERIALS AND METHODS: In November 2019, every male employee of the UKF with a minimum age of 45 yrs (or 40 yrs with a first degree relative with prostate cancer) was offered a free prostate cancer checkup. This checkup contained digital rectal examination (DRE), transrectal ultrasound and PSA (prostata-specific antigen) testing. RESULTS: Overall, 121/840 employees (14.4%) participated in the Movember campaign. A first degree relative with prostate cancer was reported in overall by 14% of the participants (n = 17). At least one prior prostate cancer check up had 33%. A total of 2.5% (n = 3) had one prior negative prostate biopsy. Median age was 54 yrs (interquartile range 50-58). Median PSA level was 0.9 ng/ml and median free-PSA 0.3 ng/ml. A suspicious DRE was found in 5% (n = 6). After stratification according to age (≤ 50 yrs vs. > 50 yrs), participants over 50 yrs had a significantly higher PSA level (1.0 ng/ml vs. 0.7 ng/ml, p < 0.01) and had more frequently at least one prior prostate cancer checkup in the past (42.0 vs. 12.1%, p < 0.01). All suspicious DREs were in the cohort > 50 yrs. Overall, 32.2% (n = 39) had at least a suspicious checkup. A total of 3.3% (n = 4) had suspicious PSA levels. 17.4% (n = 21) of the participants had a suspicious PSA ratio (< 20%) only. During follow-up, 6 prostate biopsies were performed, with the detection of one case of intermediate-risk prostate cancer (Gleason 3 + 4, pT3a, pPn1, pNx, R0). CONCLUSION: Overall, 121 employees participated in our Movember Prostate cancer checkup campaign with measurement of the PSA level. Suspicious results were recorded in 32.2%. One employee was diagnosed and successfully treated with an intermediate-risk prostate cancer.

[Metronomic chemotherapy with oral cyclophosphamide : An individual option for the metastatic castration-resistant prostate cancer patient?] / Metronomische Chemotherapie mit oralem Cyclophosphamid : Eine individuelle Option für den metastasierten kastrationsresistenten Prostatakarzinompatienten?

BACKGROUND: Multiple experimental approaches are meanwhile available for progressive metastatic castration resistant prostate cancer (mCRPC) patients after failure of guideline recommended therapy (i. e., chemotherapy and/or hormonal treatment). We evaluated the outcome of metronomic chemotherapy with cyclophosphamide (CY) in combination with low-dose prednisolone. MATERIALS AND METHODS: A total of 14 mCRPC-patients were treated with CY 50 mg/day (plus prednisolone 10 mg/day) between November 2012 and September 2017 after being resistant or unfit for chemotherapy and/or further hormonal treatment. Time to progression and overall survival (OS) were retrospectively determined by using Kaplan-Meier curves. RESULTS: Eight of 14 (57.1%) patients had undergone radical prostatectomy and 2 (14.3%) external beam radiation. All patients had at least three therapy lines and 50% had ≥5 mCRPC therapies. The median time from first diagnosis to mCRPC was 88 months; the median age was 78 years with a median baseline serum prostate-specific antigen (PSA) level of 341 ng/ml. With a median follow-up of 16.4 months, progression-free survival (PFS) was 71, 64, and 43% after 2, 4, and 6 months, respectively. Median OS was 8.1 months. No relevant adverse events occurred. CONCLUSION: Since CY is a well-tolerated medication with partially good clinical tumor control, it seems to be a convenient, individual treatment option in progressive mCRPC patients after failure of guideline recommended therapy.

[Radical prostatectomy in locally advanced prostate cancer]. / Radikale Prostatektomie beim klinisch lokal fortgeschrittenen Prostatakarzinom.

BACKGROUND: Due to an inverse stage migration, the proportion of patients with more aggressive and locally advanced prostate cancer (PCa) has increased over the last few years. The natural history in these patients shows a higher risk of local complications and worse oncologic outcome. OBJECTIVES: To analyze the impact of radical prostatectomy (RP) in patients with locally advanced PCa. MATERIALS AND METHODS: A review of the literature was performed using PubMed and MEDLINE databases focusing on articles addressing locally advanced PCa. RESULTS: Current guidelines recommend local therapy in patients with locally advanced PCa among other treatment options. Thereby no strong evidence favoring radiotherapy or RP is present. Compared to patients without local treatment, RP may improve oncologic outcome and decrease the risk of local complications. Due to more difficult surgery and an increased need of multimodal therapy, higher perioperative morbidity and worse functional outcomes compared to patients with localized PCa are reported. No reliable prospective data indicating a widespread use of neoadjuvant treatment exists. Indication for further adjuvant or salvage therapies depends on pathologic results and postoperative course. CONCLUSIONS: RP is one of the treatment options with good long-term results which can be offered to patients with locally advanced PCa. Nevertheless, patients need to be counselled especially about the worse postoperative functional outcome compared to patients with localized PCa.

Zonal NephRo Score: external validation for predicting complications after open partial nephrectomy.

PURPOSE: The aim of the study was to externally validate the Zonal NePhRO Score (ZNS) published in 2014 as latest and superior nephrometry score in terms of prediction of perioperative complications and outcome of open partial nephrectomies (OPNs). METHODS: We identified 200 consecutive patients who underwent OPN. Analysis of preoperative CT or MRI scans and retrospective analysis of the patients' clinical records were performed. Tumour complexity was stratified according to the ZNS into three categories: low (4-6), moderate (7-9) and high (10-12) complexity. Predictors for perioperative complications and surgical parameters were identified using univariate and multivariate logistic regression. RESULTS: Tumour complexity was graded in 19.8 % of the cases as low, in 50.3 % as moderate and in 29.9 % as high. In the multivariate analysis, ZNS was significantly associated with a higher complication rate (OR 1.25, 95 % CI 1.04-1.49, p = 0.014), longer ischaemia time (IT) (ß = 1.19, 95 % CI 0.33-2.05, p = 0.007), postoperative drop of estimated glomerular filtration rate (eGFR) (ß = -1.86, 95 % CI -3.71 to -0.01, p = 0.049) and opening of the collecting system (CS) (OR 1.72, 95 % CI 1.40-2.10, p < 0.001). In addition, age and body mass index were identified as independent predictors for complications (OR 1.03, 95 % CI 1.00-1.06, p = 0.043 and OR 1.08, 95 % CI 1.00-1.15, p = 0.031). CONCLUSION: The present study is the first external validation of the ZNS as a predictor of perioperative complications in patients undergoing OPN. A higher ZNS score was associated with a longer IT, a higher rate of opening the CS and drop of eGFR.

Open Partial Nephrectomy for High-Risk Renal Masses Is Associated with Renal Pseudoaneurysms: Assessment of a Severe Procedure-Related Complication.

OBJECTIVES: A symptomatic renal pseudoaneurysm (RPA) is a severe complication after open partial nephrectomy (OPN). The aim of our study was to assess incidence and risk factors for RPA formation. Furthermore, we present our management strategy. PATIENTS AND METHODS: Clinical records of consecutive patients undergoing OPN were assessed for surgical outcome and postoperative complications. Renal masses were risk stratified for tumor complexity according to the PADUA score. Uni- and multivariate analysis for symptomatic RPAs were performed using the t-tests and logistic regression. RESULTS: We identified 233 patients treated with OPN. Symptomatic RPAs were observed in 13 (5.6%) patients, on average 14 (4-42) days after surgery. Uni- and multivariate analysis identified tumor complexity to be an independent predictor for symptomatic RPAs (p = 0.004). There was a significant correlation between RPAs and transfusion and the duration of stay (p < 0.001 and p = 0.021). Symptomatic RPAs were diagnosed with CT scans and successfully treated with arterial embolization. DISCUSSION: Symptomatic RPAs are not uncommon after OPN for high-risk renal masses. A high nephrometry score is a predictor for this severe complication and may enable a risk-stratified followup. RPAs can successfully be located by CT angiography, which enables targeted angiographic treatment.

Gum acacia mitigates genetic damage in adenine-induced chronic renal failure in rats.

BACKGROUND: Subjects with chronic renal failure (CRF) exhibit oxidative genome damage, which may predispose to carcinogenesis, and Gum acacia (GumA) ameliorates this condition in humans and animals. We evaluated here renal DNA damage and urinary excretion of four nucleic acid oxidation adducts namely 8-oxoguanine (8-oxoGua), 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), 8-oxoguanosine (8-oxoGuo) and 8-hydroxy-2-deoxyguanisone (8-OHdg) in rats with adenine (ADE)-induced CRF with and without GumA treatment. MATERIALS AND METHODS: Twenty-four rats were divided into four equal groups and treated for 4 weeks. The first group was given normal food and water (control). The second group was given normal food and GumA (15% w/v) in drinking water. The third group was fed powder diet containing adenine (ADE) (0·75% w/w in feed). The fourth group was fed like in the third group, plus GumA in drinking water (15%, w/v). RESULTS: ADE feeding induced CRF (as measured by several physiological, biochemical and histological indices) and also caused a significant genetic damage and significant decreases in urinary 8-oxo Gua and 8-oxoGuo, but not in the other nucleic acids. However, concomitant GumA treatment reduced the level of genetic damage in kidney cells as detected by Comet assay and significantly reversed the effect of adenine on urinary 8-oxoGuo. CONCLUSIONS: Treatment with GumA is able to mitigate genetic damage in renal tissues of rats with ADE-induced CRF.

Influence of hepatitis C virus infection and high virus serum load on biliary complications in liver transplantation.

BACKGROUND: Biliary complications (BCs) and recurrent hepatitis C virus (HCV) infection are among the major causes of morbidity and graft loss following liver transplantation. The influence of HCV on BCs has not been definitely clarified. PATIENTS AND METHODS: We performed a retrospective cohort study to analyze risk factors and outcome of post orthotopic liver transplantation (OLT) BCs in 352 liver transplant recipients over 12 years in Munich, Germany (n = 84 with HCV; living donor and re-OLT were excluded). BCs diagnosed with imaging techniques and abnormal liver enzyme pattern, requiring an intervention, were considered. RESULTS: In a multivariate analysis, HCV serostatus and a high pre-and post-surgery HCV RNA serum load were independent risk factors for anastomotic strictures. HCV positivity and BCs alone did not alter graft loss. HCV-positive patients with BCs, however, had a significantly worse graft outcome (P = 0.02). Non-anastomotic strictures, bile leaks, and the number of interventions needed to treat bile leaks led to worse graft outcome in all patients. CONCLUSION: HCV positivity and a high HCV RNA serum load were risk factors for anastomotic strictures. BCs and HCV had an additive effect on graft loss.

Comparing acoustic radiation force impulse imaging to transient elastography to assess liver stiffness in healthy volunteers with and without valsalva manoeuvre.

PURPOSE: Acoustic Radiation Force Impulse Imaging (ARFI) is a new ultrasound elastography technology (Siemens ACUSON S2000 Virtual Touch™ Tissue Quantification), which is integrated in conventional ultrasound equipment. In preliminary studies, ARFI sheer wave speed (SWS) in liver tissue correlated well with transient elastography (TE) values and liver fibrosis stages. MATERIALS AND METHODS: Sixty-eight healthy male and female volunteers were measured with ARFI with two ultrasound tranducers, three measuring positions and during valsalva manoeuvre. A TE (FibroScan™, Echosens, France) was performed in 60 volunteers. RESULTS: Volunteers had a mean age of 28 years and a mean BMI of 22.3. There was no significant difference of ARFI SWS between the 4C1 and 4V1 ultrasound probes in either intercostal or abdominal approach to liver segment 8 but a higher variance of ARFI SWS with the 4V1/abdominal compared to the intercostal approach (p = 0.0368). The 4C1/intercostal approach had the highest success rates (97.2%), comparable to those of TE (97.18%). Left liver lobe measurements obtained both significantly higher ARFI SWS and value variance (p = 0.0016 and p = 0.0198) compared to 4C1/intercostal approach. Mean ARFI SWS was 1.19 m/s (range 0.77-1.63). Mean TE was 5.39 kPa (range 3.3-9.0 kPa). Valsalva manoeuvre did not significantly alter ARFI SWS and variance. Skin-liver distance significantly influenced ARFI SWS (p < 0.05), while age and gender did not. CONCLUSION: These results might constitute a first impression of the chances of ARFI SWS to assess liver stiffness, especially in patients with liver diseases due to increased venous pressure.

Controlling absorption of gamma radiation via nuclear level anticrossing.

A significant reduction of absorption for single gamma photons has been experimentally observed by studying Mössbauer spectra of 57Fe in a FeCO3 crystal. The experimental results have been explained in terms of a quantum interference effect involving nuclear level anticrossing due to the presence of a combined magnetic dipole and electric quadrupole interaction.

Electromagnetically induced transparency via adiabatic following of the nonabsorbing state.

It is shown that the adiabatic following of the dark, nonabsorbing state improves significantly the electromagnetically induced transparency performance and slows down the group velocity of the probe pulse. This concept can be used for fast selective gating of one pulse out of a pulse train.

Dynamics of a semiconductor laser array with delayed global coupling.

We study the dynamics of an array of single mode semiconductor lasers globally but weakly coupled by a common external feedback mirror and by nearest neighbor interactions. We seek to determine the conditions under which all lasers of the array are in phase, whether in a steady, periodic, quasiperiodic, or chaotic regime, in order to maximize the output far field intensity. We show that the delay may be a useful control parameter to achieve in-phase synchronization. For the in-phase steady state, there is a competition between a delay-induced Hopf bifurcation leading to an in-phase periodic regime and a delay-independent Hopf bifurcation leading to an antiphased periodic regime. Both regimes are described analytically and secondary Hopf bifurcations to quasiperiodic solutions are found. Close to the stable steady state, the array is described by a set of Kuramoto equations for the phases of the fields. Above the first Hopf bifurcation, these equations are generalized by the addition of second and third order time derivatives of the phases.

Instability in a laser-diode-pumped microchip Nd:YAG laser in a n-ary product scheme.

Dynamical instability, chaotic pulsations, and generalized bistability have been observed in a laser-diode-pumped microchip Nd:YAG laser operating in a double transition scheme in which lasing occurs on two transitions with overlapping gain profiles, F(3/2)(4)(2)? I(11/2)(4)(3) and F(3/2)(4)(1)? I(11/2)(4)(2), and simultaneously involves excited Nd atoms from different sublevels of the upper manifold. The modeling of the experimental results requires rate equations that include cross-gain coupling among oscillating modes that belong to different transitions whose population inversion densities are determined by the Boltzmann distribution.

Symmetry breaking and dynamical independence in a multimode laser

Multimode lasers display various behaviors caused by the asymmetry between the modes belonging to orthogonal polarizations. We discuss dynamical independence, clustering, and grouping in a solid state laser with intracavity second harmonic generation, and show that these effects result from unstable cycles lying within their invariant planes. These invariant planes are dynamically independent. The sequential or random itinerancy of limit unstable cycles lying within the invariant planes explains most of the effects caused by asymmetry.

Low frequency fluctuations in a multimode semiconductor laser with optical feedback.

We study a multimode semiconductor laser subject to a moderate optical feedback. The steady state is destabilized by either a simple Hopf bifurcation leading to in phase dynamics or by a degenerate Hopf bifurcation leading to antiphase dynamics. The degenerate bifurcation is also a source of multiple coexisting attractors. We show that a simple interpretation of the low frequency fluctuations in the multimode regime is provided by a chaotic itinerancy among the many coexisting unstable attractors produced by the degenerate Hopf bifurcation.

Global coupling with time delay in an array of semiconductor lasers

Synchronization due to a weak global coupling with time delay in a semiconductor laser array is investigated both in the cw and self-pulsing regimes. A generalized form of the Kuramoto phase equations is derived and discussed analytically. The time delay is shown to induce in-phase synchronization in all dynamical regimes. Another form of synchronization is found which leads to local extinction of self-pulsing in the array.

Phase-separation dynamics of circular domain walls in the degenerate optical parametric oscillator.

We study the dynamics of the formation of circular domain walls, which are large-intensity structures, in a degenerate optical parametric oscillator. We show that the mean-field and the propagation models predict the same increase in the domain size proportional to t(1/3) .

Multimode semiconductor laser with selective optical feedback.

We study a multimode semiconductor laser subject to moderate selective optical feedback. The steady state of the laser is destabilized by a Hopf bifurcation and exhibits a period-doubling route to chaos. We also show the existence of a heteroclinic connection between a saddle node and an unstable focus that can be associated with experimentally observed multimode low-frequency fluctuations. This heteroclinic connection coexists with a chaotic attractor resulting from the period-doubling process.