Publications by authors named "Andreas Becker"

237 Publications

Influence of Biopsy Gleason Score on the Risk of Lymph Node Invasion in Patients With Intermediate-Risk Prostate Cancer Undergoing Radical Prostatectomy.

Front Surg 2021 9;8:759070. Epub 2021 Dec 9.

Department of Urology, University Hospital Frankfurt, Frankfurt, Germany.

To analyze the influence of biopsy Gleason score on the risk for lymph node invasion (LNI) during pelvic lymph node dissection (PLND) in patients undergoing radical prostatectomy (RP) for intermediate-risk prostate cancer (PCa). We retrospectively analyzed 684 patients, who underwent RP between 2014 and June 2020 due to PCa. Univariable and multivariable logistic regression, as well as binary regression tree models were used to assess the risk of positive LNI and evaluate the need of PLND in men with intermediate-risk PCa. Of the 672 eligible patients with RP, 80 (11.9%) men harbored low-risk, 32 (4.8%) intermediate-risk with international society of urologic pathologists grade (ISUP) 1 (IR-ISUP1), 215 (32.0%) intermediate-risk with ISUP 2 (IR-ISUP2), 99 (14.7%) intermediate-risk with ISUP 3 (IR-ISUP3), and 246 (36.6%) high-risk PCa. Proportions of LNI were 0, 3.1, 3.7, 5.1, and 24.0% for low-risk, IR-ISUP1, IR-ISUP 2, IR-ISUP-3, and high-risk PCa, respectively ( < 0.001). In multivariable analyses, after adjustment for patient and surgical characteristics, IR-ISUP1 [hazard ratio (HR) 0.10, = 0.03], IR-ISUP2 (HR 0.09, < 0.001), and IR-ISUP3 (HR 0.18, < 0.001) were independent predictors for lower risk of LNI, compared with men with high-risk PCa disease. The international society of urologic pathologists grade significantly influence the risk of LNI in patients with intermediate- risk PCa. The risk of LNI only exceeds 5% in men with IR-ISUP3 PCa. In consequence, the need for PLND in selected patients with IR-ISUP 1 or IR-ISUP2 PCa should be critically discussed.
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http://dx.doi.org/10.3389/fsurg.2021.759070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8695544PMC
December 2021

Social and Nonsocial Autism Symptom Domains in Children and Adolescents with Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder: Insights into Their Symptomatological Interplay.

Psychopathology 2021 Dec 17:1-9. Epub 2021 Dec 17.

Department of Child and Adolescent Psychiatry, Faculty of Medicine, TU Dresden, Dresden, Germany.

Introduction: Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) share overlapping symptomatology, particularly with regard to social impairments (including peer relationship difficulties), and they frequently co-occur. However, the nature of their co-occurrence remains unclear. Therefore, the current study aimed to examine the nature of the transdiagnostic link between ASD and ADHD from a symptomatological point of view measured with the Autism Diagnostic Observation Schedule (ADOS Module 3) and the Autism Diagnostic Interview-Revised (ADI-R).

Methods: We analyzed the social and nonsocial ASD symptom domain scores from both diagnostic instruments in 4 clinically referred groups (i.e., ASD, ADHD, ASD + ADHD, and no psychiatric diagnosis) without other co-occurring mental disorders using a two-by-two full-factorial MANOVA design with the factors ASD (yes/no) and ADHD (yes/no).

Results: We found no ASD by ADHD interaction effects across all symptom domain scores of ADOS and ADI-R, except for ADOS imagination/creativity. There were only main effects of the factor ASD but no main effects of ADHD. Follow-up contrasts showed that exclusively, ASD had an impact on the measured symptomatology in case of co-occurring ASD + ADHD.

Conclusion: Overall, the results support an additive model of the symptomatology across areas of communication, social interaction, and stereotyped behaviors and restricted interests in case of the co-occurrence of ASD and ADHD when assessed with ADOS/ADI-R. Thus, one can assume that the phenotypic overlap of ASD + ADHD may be less complicated than suspected - at least with regard to ASD symptomatology - and that in the presence of ADHD, ASD symptomatology is generally well measurable with best-practice diagnostic instruments.
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http://dx.doi.org/10.1159/000520957DOI Listing
December 2021

Contemporary Trends and Efficacy of Pelvic Lymph Node Dissection at Radical Cystectomy for Urothelial and Variant Histology Carcinoma of the Urinary Bladder.

Clin Genitourin Cancer 2021 Nov 5. Epub 2021 Nov 5.

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada.

Objective: To test 1) contemporary pelvic lymph node dissection (PLND) trends at radical cystectomy (RC) in variant histology bladder cancer (VHBC) patients and urothelial carcinoma of the urinary bladder (UCUB), as well as 2) to test the effect of PLND extent on cancer specific mortality (CSM) after RC.

Methods: Within the Surveillance, Epidemiology and End Results Registry (SEER, 2004-2016), we identified non-metastatic stage T or T VHBC and UCUB patients, who underwent RC. CSM and lymph node invasion (LNI) rates were stratified according to PLND extent, as well as coded continuously in multivariate Cox and logistic regression models.

Results: Of 19,020 patients, 1736 (9.1%) were coded as having VHBC (46.9% squamous cell carcinoma, 22.5% adenocarcinoma, 18.9% neuroendocrine carcinoma, 11.7% not otherwise specified) vs 17,284 (90.9%) UCUB. PLND was performed in 80.1 of VHBC vs. 83.5% UCUB patients. In both histological groups, PLND rates increased over time (70.9-89.6% and 76.2%-90.1%, both P < .01). PLND extent did not significantly affect CSM in stage T or T VHBC patients. Conversely, PLND extent was associated with lower CSM in T, as well as in T UCUB patients, which was confirmed in multivariate Cox analyses (Hazard ratio [HR] 0.99, P < .001). Rates of LNI increased with extent of PLND in logistic regression analyses in stage T VHBC (Odds ratio [OR] 1.01, P = .001), stage T UCUB (OR 1.01, P < .001) and T UCUB (OR 1.01, P < .001), but not in stage T VHBC (OR 1.01, P = .3).

Conclusion: PLND rates do not differ between VHBC and UCUB patients. A potential survival benefit related to more extensive PLND is operational in UCUB patients, but not in VHBC patients.
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http://dx.doi.org/10.1016/j.clgc.2021.10.010DOI Listing
November 2021

Correlation of Urine Loss after Catheter Removal and Early Continence in Men Undergoing Radical Prostatectomy.

Curr Oncol 2021 Nov 15;28(6):4738-4747. Epub 2021 Nov 15.

Department of Urology, University Hospital Frankfurt, Goethe University Frankfurt am Main, 60323 Frankfurt am Main, Germany.

Background: To determine the correlation between urine loss in PAD-test after catheter removal, and early urinary continence (UC) in RP treated patients.

Methods: Urine loss was measured by using a standardized, validated PAD-test within 24 h after removal of the transurethral catheter, and was grouped as a loss of <1, 1-10, 11-50, and >50 g of urine, respectively. Early UC (median: 3 months) was defined as the usage of no or one safety-pad. Uni- and multivariable logistic regression models tested the correlation between PAD-test results and early UC. Covariates consisted of age, BMI, nerve-sparing approach, prostate volume, and extraprostatic extension of tumor.

Results: From 01/2018 to 03/2021, 100 patients undergoing RP with data available for a PAD-test and early UC were retrospectively identified. Ultimately, 24%, 47%, 15%, and 14% of patients had a loss of urine <1 g, 1-10 g, 11-50 g, and >50 g in PAD-test, respectively. Additionally, 59% of patients reported to be continent. In multivariable logistic regression models, urine loss in PAD-test predicted early UC (OR: 0.21 vs. 0.09 vs. 0.03; for urine loss 1-10 g vs. 11-50 g vs. >50 g, Ref: <1 g; all < 0.05).

Conclusions: Urine loss after catheter removal strongly correlated with early continence as well as a severity in urinary incontinence.
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http://dx.doi.org/10.3390/curroncol28060399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8628712PMC
November 2021

Using thrombocytopenia modeling to investigate the mechanisms underlying platelet depletion induced by pan-proteasome inhibitors.

CPT Pharmacometrics Syst Pharmacol 2021 Nov 29. Epub 2021 Nov 29.

Translational Medicine, Quantitative Pharmacology, The Healthcare Business of Merck KGaA, Darmstadt, Germany.

Pan-proteasome inhibitors (pPIs) significantly improve outcomes in patients with multiple myeloma; however, their indiscriminate inhibition of multiple proteasome and immunoproteasome subunits causes diverse toxicities, including thrombocytopenia. We investigated the mechanisms underlying the platelet depletion induced by the pPIs bortezomib, carfilzomib, and ixazomib. An established thrombocytopenia model was adapted for each compound (bortezomib, ixazomib, and carfilzomib) to compare the following two pharmacodynamic mechanisms: a reversible inhibition of new progenitor cell formation (the myelosuppression model) and a reversible effect on the function of megakaryocytes to bud new platelets (platelet formation model). Bortezomib, ixazomib, and carfilzomib plasma concentration profiles and platelet counts were extracted from the literature. Pharmacokinetic (PK) and thrombocytopenia models were developed to predict the PK of these drugs and to describe their effects on proliferating cells and platelet budding. The PK models reproduced the exposure of the three compounds at steady state well compared with those reported in the literature. Both the platelet formation and myelosuppression models seemed able to describe the platelet depletion caused by bortezomib, ixazomib, and carfilzomib. Estimated structural parameters in the myelosuppression model were in the range of the values reported in the literature, whereas the mean transit time estimated with the platelet formation model was 3-fold to 10-fold higher than the highest reported value. The model of drug-induced myelosuppression yielded estimates of structural parameters in the range of those previously reported. The platelet formation model captured the temporal variation reported in clinical studies.
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http://dx.doi.org/10.1002/psp4.12743DOI Listing
November 2021

Cancer-specific mortality after radical prostatectomy vs external beam radiotherapy in high-risk Hispanic/Latino prostate cancer patients.

Int Urol Nephrol 2022 Jan 16;54(1):81-87. Epub 2021 Nov 16.

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, QC, Canada.

Purpose: To test for differences in cancer-specific mortality (CSM) rates in Hispanic/Latino prostate cancer patients according to treatment type, radical prostatectomy (RP) vs external beam radiotherapy (EBRT).

Methods: Within the Surveillance, Epidemiology, and End Results database (2010-2016), we identified 2290 NCCN (National Comprehensive Cancer Network) high-risk (HR) Hispanic/Latino prostate cancer patients. Of those, 893 (39.0%) were treated with RP vs 1397 (61.0%) with EBRT. First, cumulative incidence plots and competing risks regression models tested for CSM differences after adjustment for other cause mortality (OCM). Second, cumulative incidence plots and competing risks regression models were refitted after 1:1 propensity score matching (according to age, PSA, biopsy Gleason score, cT-stage, cN-stage).

Results: In NCCN HR patients, 5-year CSM rates for RP vs EBRT were 2.4 vs 4.7%, yielding a multivariable hazard ratio of 0.37 (95% CI 0.19-0.73, p = 0.004) favoring RP. However, after propensity score matching, the hazard ratio of 0.54 was no longer statistically significant (95% CI 0.21-1.39, p = 0.2).

Conclusion: Without the use of strictest adjustment for population differences, NCCN high-risk Hispanic/Latino prostate cancer patients appear to benefit more of RP than EBRT. However, after strictest adjustment for baseline patient and tumor characteristics between RP and EBRT cohorts, the apparent CSM benefit of RP is no longer statistically significant. In consequence, in Hispanic/Latino NCCN high-risk patients, either treatment modality results in similar CSM outcome.
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http://dx.doi.org/10.1007/s11255-021-03055-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8732979PMC
January 2022

Differential BET Bromodomain Inhibition by Dihydropteridinone and Pyrimidodiazepinone Kinase Inhibitors.

J Med Chem 2021 11 28;64(21):15772-15786. Epub 2021 Oct 28.

Drug Discovery Department, Moffitt Cancer Center, Tampa, Florida 33612, United States.

BRD4 and other members of the bromodomain and extraterminal (BET) family of proteins are promising epigenetic targets for the development of novel therapeutics. Among the reported BRD4 inhibitors are dihydropteridinones and benzopyrimidodiazepinones originally designed to target the kinases PLK1, ERK5, and LRRK2. While these kinase inhibitors were identified as BRD4 inhibitors, little is known about their binding potential and structural details of interaction with the other BET bromodomains. We comprehensively characterized a series of known and newly identified dual BRD4-kinase inhibitors against all eight individual BET bromodomains. A detailed analysis of 23 novel cocrystal structures of BET-kinase inhibitor complexes in combination with direct binding assays and cell signaling studies revealed significant differences in molecular shape complementarity and inhibitory potential. Collectively, the data offer new insights into the action of kinase inhibitors across BET bromodomains, which may aid the development of drugs to inhibit certain BET proteins and kinases differentially.
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http://dx.doi.org/10.1021/acs.jmedchem.1c01096DOI Listing
November 2021

The Effect of 10 Most Common Nonurological Primary Cancers on Survival in Men With Secondary Prostate Cancer.

Front Oncol 2021 6;11:754996. Epub 2021 Oct 6.

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, QC, Canada.

Background: This study aims to test the effect of the 10 most common nonurological primary cancers (skin, rectal, colon, lymphoma, leukemia, pancreas, stomach, esophagus, liver, lung) on overall mortality (OM) after secondary prostate cancer (PCa).

Material And Methods: Within the Surveillance, Epidemiology, and End Results (SEER) database, patients with 10 most common primary cancers and concomitant secondary PCa (diagnosed 2004-2016) were identified and were matched in 1:4 fashion (age, year at diagnosis, race/ethnicity, treatment type, TNM stage) with primary PCa controls. OM was compared between secondary and primary PCa patients and was stratified according to primary cancer type, as well as according to time interval between primary cancer secondary PCa diagnoses.

Results: We identified 24,848 secondary PCa patients (skin,  = 3,871; rectal,  = 798; colon,  = 3,665; lymphoma,  = 2,583; leukemia,  = 1,102; pancreatic,  = 118; stomach,  = 361; esophagus,  = 219; liver,  = 160; lung,  = 1,328) 531,732 primary PCa patients. Secondary PCa characteristics were less favorable than those of primary PCa patients (PSA and grade), and smaller proportions of secondary PCa patients received active treatment. After 1:4 matching, all secondary PCa exhibited worse OM than primary PCa patients. Finally, subgroup analyses showed that the survival disadvantage of secondary PCa patients decreased with longer time interval since primary cancer diagnosis and subsequent secondary PCa.

Conclusion: Patients with secondary PCa are diagnosed with less favorable PSA and grade. Even after matching for PCa characteristics, secondary PCa patients still exhibit worse survival. However, the survival disadvantage is attenuated, when secondary PCa diagnosis is made after longer time interval, since primary cancer diagnosis.
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http://dx.doi.org/10.3389/fonc.2021.754996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8526938PMC
October 2021

Survival rates with external beam radiation therapy in newly diagnosed elderly metastatic prostate cancer patients.

Prostate 2022 Jan 11;82(1):78-85. Epub 2021 Oct 11.

Division of Urology, Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada.

Background: The survival benefit of primary external beam radiation therapy (EBRT) has never been formally tested in elderly men who were newly diagnosed with metastatic prostate cancer (mPCa). We hypothesized that elderly patients may not benefit of EBRT to the extent as younger newly diagnosed mPCa patients, due to shorter life expectancy.

Methods: We relied on Surveillance, Epidemiology and End Results (2004-2016) to identify elderly newly diagnosed mPCa patients, aged >75 years. Kaplan-Meier, univariable and multivariable Cox regression models, as well as Competing Risks Regression models tested the effect of EBRT versus no EBRT on overall mortality (OM) and cancer-specific mortality (CSM).

Results: Of 6556 patients, 1105 received EBRT (16.9%). M1b stage was predominant in both EBRT (n = 823; 74.5%) and no EBRT (n = 3908; 71.7%, p = 0.06) groups, followed by M1c (n = 211; 19.1% vs. n = 1042; 19.1%, p = 1) and M1a (n = 29; 2.6% vs. n = 268; 4.9%, p < 0.01). Median overall survival (OS) was 23 months for EBRT and 23 months for no EBRT (hazard ratio [HR]: 0.97, p = 0.6). Similarly, median cancer-specific survival (CSS) was 29 months for EBRT versus 30 months for no EBRT (HR: 1.04, p = 0.4). After additional multivariable adjustment, EBRT was not associated with lower OM or lower CSM in the entire cohort, as well as after stratification for M1b and M1c substages.

Conclusions: In elderly men who were newly diagnosed with mPCa, EBRT does not affect OS or CSS. In consequence, our findings question the added value of local EBRT in elderly newly diagnosed mPCa patients.
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http://dx.doi.org/10.1002/pros.24249DOI Listing
January 2022

The Impact of Preoperative Double-J Stent on Perioperative Complications, Recurrence, and Quality of Life in Adult Patients Undergoing Pyeloplasty.

Urol Int 2021 Oct 1:1-8. Epub 2021 Oct 1.

Department of Urology, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt, Germany.

Purpose: This study aimed to evaluate the impact of preoperative double-J stent (DJ) in pyeloplasty patients on perioperative complications, recurrence, and quality of life (QoL).

Methods: Pyeloplasties due to ureteropelvic junction obstructions between January 2010 and December 2020 were consecutively identified. A standardized follow-up questionnaire was used. Tabulation was made according to preoperative DJ versus no DJ. Subgroup analyses addressed primary robotic pyeloplasties.

Results: Of 95 pyeloplasty patients, 62% received a preoperative DJ. Patients with preoperative DJ exhibited higher rates of Clavien-Dindo (CD) 2 (22 vs. 11%) complications, but not of CD3 (8.5 vs. 8.3%, p = 0.5). After a median follow-up of 61 months, 9 patients exhibited a recurrence, of whom 7 had a preoperative DJ. In QoL assessment, comparable findings were made between patients with and without preoperative DJ. In robotic pyeloplasty patients (n = 73), patients with preoperative DJ (58%, n = 42) experienced higher CD3 complication rates, compared to patients without preoperative DJ (12 vs. 6.5%). Moreover, higher rates of recurrences were observed in preoperative DJ patients (12 vs. 3.2%).

Conclusion: In a contemporary pyeloplasty cohort, the midterm success rate was good with 91%. Our findings suggest that preoperative DJ is associated with higher recurrence rates. However, QoL did not differ between patients with and without preoperative DJ.
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http://dx.doi.org/10.1159/000519481DOI Listing
October 2021

Catheterization Does Not Improve Course of Disease in Female Patients with Acute Cystitis or Pyelonephritis: Retrospective Analysis of >300 In-Hospital Treated Patients.

Urol Int 2021 18;105(11-12):1104-1112. Epub 2021 Aug 18.

Department of Urology, University Hospital Frankfurt, Frankfurt, Germany.

Purpose: Females with in-hospital treatment for acute cystitis (AC) or pyelonephritis may benefit from catheterization at admission.

Methods: All female patients with AC or pyelonephritis requiring in-hospital treatment at University Hospital Frankfurt (2004-2019) were retrospectively analyzed. Logistic regression models were used to predict the catheter value.

Results: Of 310 female patients, 40% harbored AC versus 60% pyelonephritis, of whom 62% and 74% received a catheter at admission: C-reactive protein (CRP) and white blood count (WBC) were significantly elevated in AC and pyelonephritis catheter versus no catheter patients (both p < 0.05). Time to CRP and WBC nadir did not differ between the AC catheter versus no catheter group (both p > 0.05). Conversely, time to CRP nadir was prolonged in pyelonephritis catheter patients. AC and pyelonephritis catheter patients exhibited a prolonged antibiotic treatment and length of stay (LOS, both p < 0.05). In multivariable analyses, CRP >5 ng/mL was a predictor for receiving a catheter in all patients. In AC, a positive urine culture and fever predicted, respectively, prolonged LOS or antibiotic treatment (all p < 0.05).

Conclusion: Risk factors exist with regard to receiving a catheter and prolonged antibiotic treatment or LOS in females with AC or pyelonephritis. A catheter may not accelerate recovery or WBC nadir.
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http://dx.doi.org/10.1159/000518066DOI Listing
August 2021

Feasibility and outcome of radical prostatectomy following inductive neoadjuvant therapy in patients with suspicion of rectal infiltration.

Urol Oncol 2021 Aug 26. Epub 2021 Aug 26.

Department of Urology, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt am Main, Germany.

Objective: To determine the feasibility and outcome of radical prostatectomy (RP) following neoadjuvant therapy (NAT) in patients with initial inoperable, rectum-infiltrating cT4 prostate cancer (PCa).

Methods: From 01/2018 to 12/2020, 26 patients with clinical (DRE) or radiographical (mpMRI) suspicion of rectum infiltrating PCa at diagnosis and NAT prior to RP were retrospectively identified from our prospective institutional database. Two patients were still inoperable after NAT. Downsizing was administered for at least 20 weeks and RP was performed after excluding ongoing rectal infiltration.

Results: At diagnosis, median PSA was 42.5 ng/ml (IQR: 23.0-66.1). Inductive NAT consisted of androgen deprivation therapy (ADT) in combination with chemotherapy (n = 9) or without chemotherapy (n = 14). Median preoperative PSA was 0.93 ng/ml (IQR: 0.24-0.40). Median time from NAT to RP was 6 months (IQR: 5-7). Two patients were still inoperable after NAT. Of 24 patients undergoing RP, abortion of surgery due to inoperability was observed in 2 patients (8.4%), demonstrating a total failure rate of NAT in 4 out of 26 patients (15.4%). One patient suffered a rectal injury with consecutive colostomy (4.2%). No Clavien-Dindo complication Grade IV or V were observed. Urinary continence was achieved in 16 patients (84.2%). Sufficient erection for sexual intercourse was present in 2 patients (10.5%). All patients received adjuvant ADT with or without radiation therapy. Median PSA at 13 months was 0.08 ng/ml (IQR: 0.01-0.74).

Conclusion: RP of initially rectum infiltrating PCa is feasible and safe after inductive NAT, however complications rates tend to be higher compared to standard RP.
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http://dx.doi.org/10.1016/j.urolonc.2021.07.028DOI Listing
August 2021

Impact of comorbidities on acute kidney injury and renal function impairment after partial and radical tumor nephrectomy.

Scand J Urol 2021 Oct 24;55(5):377-382. Epub 2021 Aug 24.

Department of Urology, University Medical Center Göttingen, Göttingen, Germany.

Background: To test for the impact of patient comorbidities and medical risk factors on kidney function after partial (PN) or radical nephrectomy (RN) in renal cell carcinoma (RCC) patients with normal preoperative renal function.

Materials And Methods: From January 2011 to December 2014, 195 consecutive RCC patients with a preoperative estimated glomerular filtration rate (eGFR) > 60 ml/min/1.73 m underwent PN or RN. Stratification was performed according to postoperative acute kidney injury (AKI) vs. no AKI. Moreover, logistic regression models tested for risk factors predicting postoperative AKI and subsequent new-onset chronic kidney disease (eGFR < 60 or < 45 ml/min/1.73 m).

Results: Of all eligible patients, 127 (65.1%) exhibited AKI. AKI patients underwent more frequently RN (44.9 vs. 13.2% PN) and harbored more often preoperative diabetes (17.3 vs. 5.9% no diabetes), hypertension (46.5 vs. 23.5% no hypertension) and larger median tumor size (4.5 vs. 2.5 cm, all  < 0.05) than non-AKI patients. Moreover, after median follow-up of 14 months, 18.9% of AKI patients exhibited an eGFR < 60 ml/min/1.73 m vs. 7.4% non-AKI patients ( = 0.01). In multivariable models, hypertension and RN were risk factors for postoperative AKI (both  < 0.01). Age > 60 years and RN as well as preoperative diabetes were risk factors for postoperative eGFR < 60 or < 45 ml/min/1.73 m (all  < 0.05), respectively.

Conclusions: Postoperative AKI is a non-negligible event especially after RN that can be further triggered by comorbidities such as diabetes and hypertension. Comorbidities should be considered in clinical decision-making for RCC surgery and patients need to be counseled about the increased risk of consecutive renal function impairment.
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http://dx.doi.org/10.1080/21681805.2021.1948916DOI Listing
October 2021

Anesthetic Technique (Spinal vs. General Anesthesia) in Holmium Laser Enucleation of the Prostate: Retrospective Analysis of Procedural and Functional Outcomes among 1,159 Patients.

Urol Int 2021 Aug 17:1-8. Epub 2021 Aug 17.

Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Objective: The aim of the study was to compare procedural efficacy, early and late functional outcomes in holmium laser enucleation of the prostate (HoLEP) under spinal anesthesia (SA) versus general anesthesia (GA).

Methods: We retrospectively reviewed patients undergoing HoLEP at our institution between 2012 and 2017. Standard pre-, peri-, and postoperative characteristics were compared according to anesthetic technique. Multivariable logistic regression analyses (MVAs) were employed to study the impact of SA on procedural efficacy and postoperative complications.

Results: Our study cohort consisted of 1,159 patients, of whom 374 (32%) underwent HoLEP under SA. While a medical history of any anticoagulation/antiplatelet therapy except low-dose acetylsalicylic acid was significantly more common among patients undergoing GA (16% vs. 10%, p = 0.001), no other significant differences in preoperative characteristics were noted including age, body mass index, American Society of Anesthesiologists Classification (ASA), prostate size, or International Prostate Symptom Score (IPSS), and quality of life scores. Patients under SA exhibited shorter times of enucleation 42 min (interquartile range [IQR]:27-59 vs. 45 min [IQR: 31-68], p = 0.002), and combined time of enucleation/morcellation/coagulation (57 min [IQR: 38-85] vs. 64 min [IQR: 43-93], p = 0.002), as well as fewer complications (Clavien-Dindo ≥3) (12 [3.2%] vs. 55 [7%], p = 0.013). These associations were confirmed in MVA. Patients did not differ significantly with regard to early micturition including post-void residual volume and maximum flow-rate improvement. At a median follow-up of 33 months (IQR: 32-44), patients with SA had a lower IPSS score (median 3 [IQR: 1-6] vs. 4 [IQR: 2-7], p = 0.039). However, no significant differences were observed with respect to any urinary incontinence, urge symptoms, and postoperative pain.

Conclusion: In this large retrospective series, HoLEP under SA was a safe and efficacious procedure with comparable early and long-term functional outcomes.
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http://dx.doi.org/10.1159/000517542DOI Listing
August 2021

Influence of Tumor Burden on Serum Prostate-Specific Antigen in Prostate Cancer Patients Undergoing Radical Prostatectomy.

Front Oncol 2021 29;11:656444. Epub 2021 Jul 29.

Department of Urology, University Hospital Frankfurt, Frankfurt am Main, Germany.

Objective: We aimed to assess the correlation between serum prostate-specific antigen (PSA) and tumor burden in prostate cancer (PCa) patients undergoing radical prostatectomy (RP), because estimation of tumor burden is of high value, e.g., in men undergoing RP or with biochemical recurrence after RP.

Patients And Methods: From January 2019 to June 2020, 179 consecutive PCa patients after RP with information on tumor and prostate weight were retrospectively identified from our prospective institutional RP database. Patients with preoperative systemic therapy (n=19), metastases (cM1, n=5), and locally progressed PCa (pT4 or pN1, n=50) were excluded from analyses. Histopathological features, including total weight of the prostate and specific tumor weight, were recorded by specialized uro-pathologists. Linear regression models were performed to evaluate the effect of PSA on tumor burden, measured by tumor weight after adjustment for patient and tumor characteristics.

Results: Overall, median preoperative PSA was 7.0 ng/ml (interquartile range [IQR]: 5.41-10) and median age at surgery was 66 years (IQR: 61-71). Median prostate weight was 34 g (IQR: 26-46) and median tumor weight was 3.7 g (IQR: 1.8-7.1), respectively. In multivariable linear regression analysis after adjustment for patients and tumor characteristics, a significant, positive correlation could be detected between preoperative PSA and tumor weight (coefficient [coef.]: 0.37, CI: 0.15-0.6, p=0.001), indicating a robust increase in PSA of almost 0.4 ng/ml per 1g tumor weight.

Conclusion: Preoperative PSA was significantly correlated with tumor weight in PCa patients undergoing RP, with an increase in PSA of almost 0.4 ng/ml per 1 g tumor weight. This might help to estimate both tumor burden before undergoing RP and in case of biochemical recurrence.
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http://dx.doi.org/10.3389/fonc.2021.656444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358926PMC
July 2021

Median time to progression with TKI-based therapy after failure of immuno-oncology therapy in metastatic kidney cancer: A systematic review and meta-analysis.

Eur J Cancer 2021 09 12;155:245-255. Epub 2021 Aug 12.

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada.

Background: The efficacy of tyrosine kinase inhibitor (TKI)-based therapy after previous immuno-oncology therapy (IO) failure has been addressed before. However, summary efficacy estimates have never been generated in these reports. We addressed this void.

Material And Methods: We systematically examined TKI efficacy after IO-failure and generated weighted median progression-free survival (PFS) estimates for Pazopanib, Axitinib, Cabozantinib, Sunitinib. A systematic review according to PRISMA was conducted. PubMed and abstracts were queried. Only studies proving median PFS were included. Weighted medians were computed for each TKI alternative.

Results: Of 245 articles, nine eligible studies were included in the current study with 952 analysed patients. Weighted PFS medians after any previous IO-based therapy were respectively 13.7 (range from 4.6 to 24.4), 8.1 (range from 4.7 to 13.2), 8.5 (range from 4.7 to 15.2) and 6.9 months (range from 2.9 to 11.6) for Pazopanib, Axitinib, Cabozantinib, Sunitinib. Specific second-line weighted PFS median was 14.8 months (range from 5.6 to 24.4), 10.1 months (range from 6.4 to 13.2), 8.7 months (range from 4.7 to 15.2) and 6.0 months (range from 2.9 to 8.0) for Pazopanib, Axitinib, Cabozantinib, Sunitinib, respectively, after first-line IO.

Conclusion: Pazopanib results in the longest weighted median PFS, after previous IO-failure, regardless of treatment line, as well as in specific second-line, post-first-line IO failure settings. Pending novel studies, Pazopanib appears to represent the most promising treatment option after prior IO.
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http://dx.doi.org/10.1016/j.ejca.2021.07.014DOI Listing
September 2021

[Reality of care of colorectal cancer in the State of Brandenburg : With special consideration of the number of hospital cases and certification as a colorectal cancer center].

Chirurg 2021 Aug 10. Epub 2021 Aug 10.

Medizinische Hochschule Brandenburg Theodor Fontane, Hochstraße 29, 14770, Brandenburg, Deutschland.

Analysis of the quality of care for colorectal cancer is an essential foundation for further development and is based on the comparison of the goals set and the actual quality of care. This publication presents the reality of care in the State of Brandenburg covering the complete spectrum of treating clinics based on the data of the clinical cancer register. This study analyzed the number of resected and examined lymph nodes, the quality of total mesorectal excision (TME), the residual tumor (R0) resection rate and the proportion of adjuvant therapy of colon cancer in Union internationale contre le cancer (UICC) stage III depending on the operation quota of hospitals and the certification as bowel cancer center according to Onkozert. Apart from the R status, the analyses showed no differences in the qualitative operation data from the clinical cancer register depending on the hospital volume.
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http://dx.doi.org/10.1007/s00104-021-01468-9DOI Listing
August 2021

Regional differences in patient age and prostate cancer characteristics and rates of treatment modalities in favorable and unfavorable intermediate risk prostate cancer across United States SEER registries.

Cancer Epidemiol 2021 10 5;74:101994. Epub 2021 Aug 5.

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada.

Background: Intermediate risk (IR) prostate cancer (PCa) is a highly heterogeneous entity and can be distinguished into favorable and unfavorable IR PCa according to biopsy, PSA and cT-stage characteristics. These differences may translate into differences in treatment type.

Methods: We tested for differences in PCa tumor characteristics and differences in active treatment rates (radical prostatectomy [RP], external beam radiotherapy [EBRT]) according to Surveillance, Epidemiology and End Results (SEER) registry (2010-2015) in favorable and unfavorable IR PCa. Data were stratified according to individual SEER registries. Further analyses additionally adjusted for PCa baseline characteristics (PSA, cT stage, biopsy Gleason group grading [GGG], percentage of positive biopsy cores).

Results: Tabulations according to SEER registries showed that, in favorable IR vs. unfavorable IR, the rates of RP and EBRT respectively ranged from 30.0 to 54.3% vs. 30.3-55.5 % and 8.3-44.7 % vs. 11.5-45.5 %. Differences in age and baseline PCa tumor characteristics also existed in both favorable and unfavorable IR across SEER registries. After adjustment for those baseline patient and PCa characteristics (PSA, cT stage, GGG, percentage of positive biopsy cores), RP and EBRT rates exhibited virtually no residual differences across individual SEER registries, in both favorable (36.0-41.0 % and 26.8-28.1 %) and unfavorable IR PCa (39.2-42.0% and 31.1-33.5 %).

Conclusion: Important differences may be identified in treatment rates within the examined 18 SEER registries in favorable and in unfavorable IR PCa. However, the observed differences are virtually entirely explained by differences in baseline PCa characteristics.
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http://dx.doi.org/10.1016/j.canep.2021.101994DOI Listing
October 2021

Nomogram Predicting Downgrading in National Comprehensive Cancer Network High-risk Prostate Cancer Patients Treated with Radical Prostatectomy.

Eur Urol Focus 2021 Jul 29. Epub 2021 Jul 29.

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada.

Background: Some high-risk prostate cancer (PCa) patients may show more favorable Gleason pattern at radical prostatectomy (RP) than at biopsy.

Objective: To test whether downgrading could be predicted accurately.

Design, Setting, And Participants: Within the Surveillance, Epidemiology and End Results database (2010-2016), 6690 National Comprehensive Cancer Network (NCCN) high-risk PCa patients were identified.

Outcome Measurements And Statistical Analyses: We randomly split the overall cohort between development and validation cohorts (both n = 3345, 50%). Multivariable logistic regression models used biopsy Gleason, prostate-specific antigen, number of positive prostate biopsy cores, and cT stage to predict downgrading. Accuracy, calibration, and decision curve analysis (DCA) tested the model in the external validation cohort.

Results And Limitations: Of 6690 patients, 50.3% were downgraded at RP, and of 2315 patients with any biopsy pattern 5, 44.1% were downgraded to RP Gleason pattern ≤4 + 4. Downgrading rates were highest in biopsy Gleason pattern 5 + 5 (84.1%) and lowest in 3 + 4 (4.0%). In the validation cohort, the logistic regression model-derived nomogram predicted downgrading with 71.0% accuracy, with marginal departures (±3.3%) from ideal predictions in calibration. In DCA, a net benefit throughout all threshold probabilities was recorded, relative to treat-all or treat-none strategies and an algorithm based on an average downgrading rate of 50.3%. All steps were repeated in the subgroup with any biopsy Gleason pattern 5, to predict RP Gleason pattern ≤4 + 4. Here, a second nomogram (n = 2315) yielded 68.0% accuracy, maximal departures from ideal prediction of ±5.7%, and virtually the same DCA pattern as the main nomogram.

Conclusions: Downgrading affects half of all high-risk PCa patients. Its presence may be predicted accurately and may help with better treatment planning.

Patient Summary: Downgrading occurs in every second high-risk prostate cancer patients. The nomograms developed by us can predict these probabilities accurately.
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http://dx.doi.org/10.1016/j.euf.2021.07.008DOI Listing
July 2021

Design of the UWB Positioning System Simulator for LOS/NLOS Environments.

Sensors (Basel) 2021 Jul 12;21(14). Epub 2021 Jul 12.

Faculty of Information Technology, University of Applied Science and Arts, Sonnenstr. 96, 44139 Dortmund, Germany.

UWB is a rapidly developing technology characterised by high positioning accuracy, additional data transferability, and communication security. Low costs and energy demand makes it a system that meets the requirements of smart cities (e.g., smart mobility). The analysis of the positioning accuracy of moving objects requires a ground truth. For the UWB system, it should have an accuracy of the order of millimetres. The generated data can be used to minimize the cost and time needed to perform field tests. However, there is no UWB simulators which can consider the variable characteristics of operation along with distance to reflect the operation of real systems. This article presents a 2D UWB simulator for outdoor open-air areas with obstacles and a method of analysing data from the real UWB system under line-of-sight (LOS) and non-line-of-sight conditions. Data are recorded at predefined outdoor reference distances, and by fitting normal distributions to this data and modelling the impact of position changes the real UWB system can be simulated and it makes it possible to create virtual measurements for other locations. Furthermore, the presented method of describing the path using time-dependent equations and obstacles using a set of inequalities allows for reconstructing the real test scenario with moving tags with high accuracy.
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http://dx.doi.org/10.3390/s21144757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8309887PMC
July 2021

Cystatin C predicts renal function impairment after partial or radical tumor nephrectomy.

Int Urol Nephrol 2021 Oct 16;53(10):2041-2049. Epub 2021 Jul 16.

Department of Urology, University Medical Center Göttingen, Göttingen, Germany.

Purpose: To test the value of preoperative and postoperative cystatin C (CysC) as a predictor on kidney function after partial (PN) or radical nephrectomy (RN) in renal cell carcinoma (RCC) patients with normal preoperative renal function.

Methods: From 01/2011 to 12/2014, 195 consecutive RCC patients with a preoperative estimated glomerular filtration rate (eGFR) > 60 ml/min/1.73m underwent surgical RCC treatment with either PN or RN. Logistic and linear regression models tested for the effect of CysC as a predictor of new-onset chronic kidney disease in follow-up (eGFR < 60 ml/min/1.73m). Moreover, postoperative CysC and creatinine values were compared for kidney function estimation.

Results: Of 195 patients, 129 (66.2%) underwent PN. In postoperative and in follow-up setting (median 14 months, IQR 10-20), rates of eGFR < 60 ml/min/1.73m were 55.9 and 30.2%. In multivariable logistic regression models, preoperative CysC [odds ratio (OR): 18.3] and RN (OR: 13.5) were independent predictors for a reduced eGFR < 60 ml/min/1.73m in follow-up (both p < 0.01), while creatinine was not. In multivariable linear regression models, a difference of the preoperative CysC level of 0.1 mg/dl estimated an eGFR decline in follow-up of about 5.8 ml/min/1.73m. Finally, we observed a plateau of postoperative creatinine values in the range of 1.2-1.3 mg/dl, when graphically depicted vs. postoperative CysC values ('creatinine blind area').

Conclusion: Preoperative CysC predicts renal function impairment following RCC surgery. Furthermore, CysC might be superior to creatinine for renal function monitoring in the early postoperative setting.
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http://dx.doi.org/10.1007/s11255-021-02957-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8463386PMC
October 2021

Immunohistochemistry for Prostate Biopsy-Impact on Histological Prostate Cancer Diagnoses and Clinical Decision Making.

Curr Oncol 2021 06 9;28(3):2123-2133. Epub 2021 Jun 9.

Department of Urology, University Hospital Frankfurt, Goethe University Frankfurt, 60590 Frankfurt, Germany.

Background: To test the value of immunohistochemistry (IHC) staining in prostate biopsies for changes in biopsy results and its impact on treatment decision-making.

Methods: Between January 2017-June 2020, all patients undergoing prostate biopsies were identified and evaluated regarding additional IHC staining for diagnostic purpose. Final pathologic results after radical prostatectomy (RP) were analyzed regarding the effect of IHC at biopsy.

Results: Of 606 biopsies, 350 (58.7%) received additional IHC staining. Of those, prostate cancer (PCa) was found in 208 patients (59.4%); while in 142 patients (40.6%), PCa could be ruled out through IHC. IHC patients harbored significantly more often Gleason 6 in biopsy ( < 0.01) and less suspicious baseline characteristics than patients without IHC. Of 185 patients with positive IHC and PCa detection, IHC led to a change in biopsy results in 81 (43.8%) patients. Of these patients with changes in biopsy results due to IHC, 42 (51.9%) underwent RP with 59.5% harboring ≥pT3 and/or Gleason 7-10.

Conclusions: Patients with IHC stains had less suspicious characteristics than patients without IHC. Moreover, in patients with positive IHC and PCa detection, a change in biopsy results was observed in >40%. Patients with changes in biopsy results partly underwent RP, in which 60% harbored significant PCa.
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http://dx.doi.org/10.3390/curroncol28030197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293248PMC
June 2021

Dysregulation profile (DP) as a transdiagnostic psychopathological factor in clinically referred children - comparisons between disorders and latent structure.

Nord J Psychiatry 2022 Jan 15;76(1):71-79. Epub 2021 Jun 15.

Department of Child and Adolescent Psychiatry and Psychotherapy, University Medical Center of Goettingen, Goettingen, Germany.

Background: Dysregulation Profile (DP) describes the psychopathological construct of concurrent impairments in the ability to regulate emotion, behaviour, and cognition measured by the Child Behaviour Checklist (CBCL). Such transdiagnostic dimensions of psychopathology play an important role in addition to core symptoms of psychiatric diagnosis in clinical practice. Evaluation of DP in children with different mental disorders may improve our understanding and treatment of both contents.

Methods: 911 clinically referred children between 6 and 18years were investigated. The sample consisted of five 'pure' disorders groups, that is, tic disorder (TIC), anxiety disorder, obsessive compulsive disorder, depression, Attention Deficit Hyperactivity Disorder (ADHD), and two comorbid disorder group, that is, ADHD + TIC and ADHD + oppositional defiant disorder (ODD). DP level and latent structure were compared across groups.

Results: The rate of severe/abnormal dysregulation rates varied from 15% to 44% when the 210 cut-off was used, and 5% to 18% when stringent cut-off was used (i.e. ≥70 on all DP-subscales). The most affected population were children with comorbid ADHD with ODD/TIC, while least were those with TIC only. Five different latent phenotypes of DP were found.

Conclusion: DP above clinical cut-off level widely exists in clinically referred children in parallel to core symptoms of their diagnosis, especially among children with comorbidities. During clinical assessment it would be worth to clarify the role of DP-related problems within the general psychosocial impairment of the patient to improve a personalized approach.
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http://dx.doi.org/10.1080/08039488.2021.1936167DOI Listing
January 2022

Environment Mapping Using Sensor Fusion of 2D Laser Scanner and 3D Ultrasonic Sensor for a Real Mobile Robot.

Sensors (Basel) 2021 May 4;21(9). Epub 2021 May 4.

Department of Electronics, Electrical Engineering and Microelectronics, Silesian University of Technology, Akademicka 16, 44-100 Gliwice, Poland.

Mapping the environment is necessary for navigation, planning and manipulation. In this paper, a fusion framework (as data-in-decision-out) is introduced for a 2D LIDAR and a 3D ultrasonic sensor to achieve three-dimensional mapping without expensive 3D LiDAR scanner or visual processing. Two sensor models are proposed for the two sensors used for map updating. Furthermore, 2D/3D map representations are discussed for our fusion approach. We also compare different probabilistic fusion methods and discuss criterias for choosing appropriate methods. Experiments are carried out with a real ground robot platform in an indoor environment. The 2D and 3D map results demonstrate that our approach is able to show the surrounding in more details. Sensor fusion provides a better estimation of the environment and the ego-pose whilst lowering the necessary resources. This gives the robot's perception of the environment more information by using only one additional low-cost 3D ultrasonic sensor. This is especially important for robust and light-weight robots with limited resources.
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http://dx.doi.org/10.3390/s21093184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124335PMC
May 2021

Correlation of MRI-Lesion Targeted Biopsy vs. Systematic Biopsy Gleason Score with Final Pathological Gleason Score after Radical Prostatectomy.

Diagnostics (Basel) 2021 May 15;11(5). Epub 2021 May 15.

Department of Urology, University Hospital Frankfurt, University Frankfurt, 60590 Frankfurt, Germany.

Background: The impact of MRI-lesion targeted (TB) and systematic biopsy (SB) Gleason score (GS) as a predictor for final pathological GS still remains unclear.

Methods: All patients with TB + SB, and subsequent radical prostatectomy (RP) between 01/2014-12/2020 were analyzed. Rank correlation coefficient predicted concordance with pathological GS for patients' TB and SB GS, as well as for the combined effect of SB + TB.

Results: Of 159 eligible patients, 77% were biopsy naïve. For SB taken in addition to TB, a Spearman's correlation of +0.33 was observed regarding final GS. Rates of concordance, upgrading, and downgrading were 37.1, 37.1 and 25.8%, respectively. For TB, a +0.52 correlation was computed regarding final GS. Rates of concordance, upgrading and downgrading for TB biopsy GS were 45.9, 33.3, and 20.8%, respectively. For the combination of SB + TB, a correlation of +0.59 was observed. Rates of concordance, upgrading and downgrading were 49.7, 15.1 and 35.2%, respectively. The combined effect of SB + TB resulted in a lower upgrading rate, relative to TB and SB (both < 0.001), but a higher downgrading rate, relative to TB ( < 0.01).

Conclusions: GS obtained from TB provided higher concordance and lower upgrading and downgrading rates, relative to SB GS with regard to final pathology. The combined effect of SB + TB led to the highest concordance rate and the lowest upgrading rate.
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http://dx.doi.org/10.3390/diagnostics11050882DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155831PMC
May 2021

Radical Cystectomy vs. Multimodality Treatment in T2N0M0 Bladder Cancer: A Population-based, Age-matched Analysis.

Clin Genitourin Cancer 2021 08 8;19(4):e264-e271. Epub 2021 Apr 8.

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada.

Background: Controversy still exists regarding efficacy of multimodality treatment (MMT) vs. radical cystectomy (RC) for urothelial carcinoma of the urinary bladder (UCUB).

Methods: Within the SEER database (2004-2016), we retrospectively identified patients with stage T2N0M0 UCUB. Competing risks regression (CRR) tested cancer-specific mortality (CSM) and adjusted for other-cause mortality after MMT vs. RC. Exact matching for age was applied. Subgroup analyses focused on differences in chemotherapy or lymph node dissection rates. In sensitivity analyses, we accounted for 40% understaging rate in patients who underwent MMT.

Results: Of 9862 patients with TNM UCUB, 2675 (27.1%) underwent MMT vs. 5751 (58.3%) RC vs. 1436 (14.6%) radiotherapy (RT) without chemotherapy. MMT rate increased (annually +3.0%, P < .01) and MMT patient age was significantly higher (median 77 years) than RC patient age (68 years). In exact age-matched analyses, 10-year CSM rates were 44.3% vs. 25.9% for MMT vs. RC (multivariate hazard ratio [HR] 0.48); 44.1% vs. 22.8% for MMT vs. RC with chemotherapy (HR 0.43); 40.5% vs. 31.1% for MMT vs. RC without lymph node dissection (HR 0.66), and 55.6% vs. 27.3% for RT without chemotherapy vs. RC (HR 0.37, all P < .001). Sensitivity analyses that addressed understaging of patients who underwent MMT resulted in virtually the same CSM rates.

Conclusion: In patents with TNM, MMT or even more so RT alone may be associated with higher CSM than RC, even in exact age-matched multivariate CRR analyses, which adjust for other-cause mortality. In consequence, patients with T2 UCUB should be informed of this possible CSM disadvantage outside of highly specialized centers.
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http://dx.doi.org/10.1016/j.clgc.2021.03.010DOI Listing
August 2021

Impact of Time to Castration Resistance on Survival in Metastatic Hormone Sensitive Prostate Cancer Patients in the Era of Combination Therapies.

Front Oncol 2021 23;11:659135. Epub 2021 Apr 23.

Department of Urology, University Hospital Frankfurt, Goethe University Frankfurt am Main, Frankfurt, Germany.

Background: To evaluate the impact of time to castration resistance (TTCR) in metastatic hormone-sensitive prostate cancer (mHSPC) patients on overall survival (OS) in the era of combination therapies for mHSPC.

Material And Methods: Of 213 mHSPC patients diagnosed between 01/2013-12/2020 who subsequently developed metastatic castration resistant prostate cancer (mCRPC), 204 eligible patients were analyzed after having applied exclusion criteria. mHSPC patients were classified into TTCR <12, 12-18, 18-24, and >24 months and analyzed regarding OS. Moreover, further OS analyses were performed after having developed mCRPC status according to TTCR. Logistic regression models predicted the value of TTCR on OS.

Results: Median follow-up was 34 months. Among 204 mHSPC patients, 41.2% harbored TTCR <12 months, 18.1% for 12-18 months, 15.2% for 18-24 months, and 25.5% for >24 months. Median age was 67 years and median PSA at prostate cancer diagnosis was 61 ng/ml. No differences in patient characteristics were observed (all p>0.05). According to OS, TTCR <12 months patients had the worst OS, followed by TTCR 12-18 months, 18-24 months, and >24 months, in that order (p<0.001). After multivariable adjustment, a 4.07-, 3.31-, and 6.40-fold higher mortality was observed for TTCR 18-24 months, 12-18 months, and <12 months patients, relative to TTCR >24 months (all p<0.05). Conversely, OS after development of mCRPC was not influenced by TTCR stratification (all p>0.05).

Conclusion: Patients with TTCR <12 months are at the highest OS disadvantage in mHSPC. This OS disadvantage persisted even after multivariable adjustment. Interestingly, TTCR stratified analyses did not influence OS in mCRPC patients.
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http://dx.doi.org/10.3389/fonc.2021.659135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103198PMC
April 2021

The Influence of Martensitic Intercalations in Magnetic Shape Memory NiCoMnAl Multilayered Films.

Entropy (Basel) 2021 Apr 14;23(4). Epub 2021 Apr 14.

Faculty of Physics, Bielefeld University, P.O. Box 100131, 33501 Bielefeld, Germany.

Hysteresis and transformation behavior were studied in epitaxial NiCoMnAl magnetic shape memory alloy thin films with varying number martensitic intercalations (MIs) placed in between. MIs consists of a different NiCoMnAl composition with a martensitic transformation occurring at much higher temperature than the host composition. With increasing number of intercalations, we find a decrease in hysteresis width from 17 K to 10 K. For a large difference in the layers thicknesses this is accompanied by a larger amount of residual austenite. If the thicknesses become comparable, strain coupling between them dominates the transformation process, which manifests in a shift of the hysteresis to higher temperatures, splitting of the hysteresis in sub hysteresis and a decrease in residual austenite to almost 0%. A long-range ordering of martensite and austenite regions in the shape of a 3D checker board pattern is formed at almost equal thicknesses.
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http://dx.doi.org/10.3390/e23040462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069775PMC
April 2021

Headache Is Associated with Low Systolic Blood Pressure and Psychosocial Problems in German Adolescents: Results from the Population-Based German KiGGS Study.

J Clin Med 2021 Apr 3;10(7). Epub 2021 Apr 3.

Clinic for Psychosomatic Medicine and Psychotherapy, University Medical Center Göttingen (UMG), Waldweg 33, D-37075 Göttingen, Germany.

Studies have reported controversial results on the relationship between headache and blood pressure. The aim of this post hoc study was twofold: first, to further investigate this relationship and, second, to assess the impact of psychosocial factors on this association in a population-based study of German children and adolescents. The analysis was conducted on study participants aged between 11 and 17 years ( = 5221, weighted from the total study cohort) from the nationwide German Health Interview and Examination Survey for Children and Adolescents (KiGGS). Health-related quality of life was assessed by self- and parent-rated German-language KINDL-R questionnaires (Children's Quality of Life Questionnaire), while mental problems were analyzed using the Strengths and Difficulties Questionnaire (SDQ). Our findings confirmed that blood pressure was significantly lower in adolescents reporting episodes of headache than in those without headache (114.0 ± 10.2 mmHg vs. 115.5 ± 11.0 mmHg, < 0.001). Logistic regression models adjusted to sex, age, body mass index, contraceptive use, and serum magnesium concentration demonstrated that headache was significantly associated with self-rated KINDL-R (Exp(B) = 0.96, 95% confidence interval (95% Cl) = 0.96-0.97, < 0.001), parent-rated KINDL-R (Exp(B) = 0.97, 95% CI = 0.96-0.98, < 0.001), as well as self-rated SDQ (Exp(B) = 1.08, 95% CI = 1.07-1.10, < 0.001), and parent-rated SDQ (Exp(B) = 1.05, 95% CI = 1.04-1.06, < 0.001). There was evidence that quality of life and mental problems mediated the effect of blood pressure on headache, as revealed by mediation models. Our results from the nationwide, representative KiGGS survey showed that low blood pressure is a significant predictor of headache, independent of quality of life and mental problems. However, these psychosocial factors may mediate the effect of blood pressure on headache in a still unknown manner.
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http://dx.doi.org/10.3390/jcm10071492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038357PMC
April 2021

Salvage Radical Prostatectomy: Baseline Prostate Cancer Characteristics and Survival Across SEER Registries.

Clin Genitourin Cancer 2021 08 19;19(4):e255-e263. Epub 2021 Mar 19.

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada.

Objective: To test for baseline prostate cancer characteristics and survival differences after salvage radical prostatectomy (SRP) across 18 Surveillance, Epidemiology and End Results (SEER) registries from 2004 to 2016.

Methods: We tabulated prostate-specific antigen (PSA), cT stage, age, and SRP rates across individual SEER registries. Kaplan-Meier and competing risks regression methodologies depicted cancer-specific mortality and other cause mortality. Finally, overall mortality was compared with predicted life expectancy.

Results: Overall, 428 SRP patients (2004-2016) were identified in the SEER database. Median follow-up duration was 74 months (interquartile range [IQR], 31-114). The median age at diagnosis was 68 years (IQR, 61-73 years) with a median PSA at diagnosis of 8.8 ng/mL (IQR, 5.4-18.6 ng/mL) and 10% cT3-4 stage (0%-23.8%). Variability existed across individual SEER registries regarding age, PSA, cT stage, and annual number of SRPs (0-17), as well as cumulative numbers of SRPs (7-73) between 2004 and 2016. At 10 years, cancer-specific mortality was 23.2% vs. other cause mortality 19.3%. Finally, SRP patients exhibited higher 10-year overall mortality (43.3%) than predicted by life tables (31.8%).

Conclusion: SRP is rarely performed. In most SEER registries, SRP use is very occasional. More than 2 average annual SRPs were reported in only 5 of all registries. Nonetheless, across all registries, SRP patients showed marginal to moderate differences in PSA, cT stage, and age at diagnosis. However, at 10 years of follow-up, 1 of 5 SRP patients died of other causes and observed overall mortality was higher than expected (36%).
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http://dx.doi.org/10.1016/j.clgc.2021.03.015DOI Listing
August 2021
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