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1.
Support Care Cancer ; 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477972

RESUMO

OBJECTIVES: To explore men's onset and burden of lower limb lymphedema (LLL) after radical prostatectomy (RP) with pelvic lymph node dissection (PLND). PATIENTS AND METHODS: A cross-sectional survey-based study was conducted nation-wide and web-based in Germany. Part 1 included 15 multidisciplinary compiled questions with three questions from the Short Form 12 Health Survey (SF-12) and the WHO activity recommendation and part 2 included the validated German Lymph-ICF-Questionnaire (Lymph-ICF-LL). Subgroup comparisons and simple regression analyses were used to identify factors associated with therapy and burden of LLL, followed by multiple regression analyses to explain variance in impairment in the patients' daily life. RESULTS: Fifty-four patients completed the survey. Median time of LLL-onset was reported with 2.0 (0.5-9.75) months after RP. Nineteen patients (35.2%) reported bilateral lymphedema, 28 (51.9%) the use of individually fitted compression stockings (CS), 25 (46.3%) of manual lymphatic drainage (LD), and 26 (48.1%) complete regression. The Lymph-ICF-LL revealed a higher total burden for patients with an active LLL compared to complete regression (total score: 25.5 vs. 11.9, p = 0.01) especially for "physical function" (28.3 vs. 12.9, p < 0.01) and "mental function" (26.2 vs. 6.7, p < 0.01). In multiple linear regression analysis, a higher BMI (ß = 0.28), lower subjective general health (ß = -0.48), and active lymphedema (ß = 0.28) were significant predictors of higher reported impairments in the Lymph-ICF-LL, accounting for 45.4% of variance. CONCLUSION: Men with LLL after RP with PLND report a significant burden in daily life. Basic therapy needs to be offered early. Postoperative onset of LLL is variable, which should be considered when assessing complications after RP.

2.
Radiologe ; 61(9): 829-838, 2021 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-34251481

RESUMO

CLINICAL/METHODOLOGICAL ISSUE: Multiparametric magnetic resonance imaging (mpMRI) of the prostate plays a crucial role in the diagnosis and local staging of primary prostate cancer. STANDARD RADIOLOGICAL METHODS: Image-guided biopsy techniques such as MRI-ultrasound fusion not only allow guidance for targeted tissue sampling of index lesions for diagnostic confirmation, but also improve the detection of clinically significant prostate cancer. METHODOLOGICAL INNOVATIONS: Minimally invasive, focal therapies of localized prostate cancer complement the treatment spectrum, especially for low- and intermediate-risk patients. PERFORMANCE: In patients of low and intermediate risk, MR-guided, minimally invasive therapies could enable local tumor control, improved functional outcomes and possible subsequent therapy escalation. Further study results related to multimodal approaches and the application of artificial intelligence (AI) by machine and deep learning algorithms will help to leverage the full potential of focal therapies for prostate cancer in the upcoming era of precision medicine. ACHIEVEMENTS: Completion of ongoing randomized trials comparing each minimally invasive therapy approach with established whole-gland procedures is needed before minimally invasive therapies can be implemented into existing treatment guidelines. PRACTICAL RECOMMENDATIONS: This review article highlights minimally invasive therapies of prostate cancer and the key role of mpMRI for planning and conducting these therapies.


Assuntos
Inteligência Artificial , Neoplasias da Próstata , Humanos , Biópsia Guiada por Imagem , Imageamento por Ressonância Magnética , Masculino , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/cirurgia
3.
Urology ; 2021 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-34153367

RESUMO

OBJECTIVE: To examine the disease-specific survival(DSS) after checkpoint inhibitor(CPI) therapy based on FGFR alterations and FGFR mRNA expression levels in patients with metastatic urothelial cancer(mUCa) within a multi-center cohort. METHODS: Within a cohort of 72 patients with mUCa from five academic centers in Germany FGFR alterations, as well as FGFR1-4 mRNA expression levels in tumor samples from the primary tumor or metastatic sites. Spearman rank correlations, logistic regression, as well as Kaplan-Meier survival analyses and univariate Cox proportional hazards regression models were employed to examine the impact of different FGFR patterns on the DSS after CPI treatment. RESULTS: FGFR3 mutations or gene fusions (gene alterations) were detected in 16.9% of all samples. Patients with or without FGFR3 gene alterations did not show different oncological outcomes undergoing CPI treatment. Low expression of FGFR2 mRNA alone, as well as the combination of either low FGFR2mRNA expression and FGFR3 gene alteration or high FGFR3mRNA expression (P = 0.027), identified a subgroup of patients with unfavorable outcomes, comprising 40% of the total cohort. This trend was also observed in univariate Cox proportional hazards regression analysis(FGFR3 gene alteration: Hazard ratio(HR) 5.33, 95%Confidence interval(CI)1.76-15.0, P = 0.004; FGFR3mRNA expression:HR 3.04, 95%CI 1.40-7.13, P = 0.005). CONCLUSION: Assessment of FGFR mRNA expression identified a high-risk subgroup of patients with mUCa. These patients showing overexpression of FGFR3 mRNA were found to have unfavorable DSS after CPI treatment. Using this approach may be suitable for identifying a patient population with poor response to CPI treatment, which may benefit from early FGFR inhibition.

4.
Urol Oncol ; 39(8): 499.e1-499.e8, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34134925

RESUMO

BACKGROUND: The cell surface interleukin 22 (IL-22) receptor complex is mainly expressed in epithelial and tissue cells like pancreatitis cells. Recent studies described that IL-22R was overexpressed in malignant diseases and was associated with a poor overall survival (OS). The role of IL-22RA1 gene expression in muscle invasive bladder cancer (MIBC) has not been investigated, yet. OBJECTIVES: The aim of this study was to analyze the role of IL-22RA1 gene expression in patients with MIBC. METHODS: In a cohort of 114 patients with MIBC who underwent radical cystectomy, IL-22RA1 gene expression was analyzed with qRT-PCR and correlated with clinical parameters. Furthermore, Kaplan-Meier and Cox regression analysis were performed. For validation, an in silico dataset (TCGA 2017, n=407) was reanalyzed. RESULTS: IL-22RA1 gene expression was independent of clinicopathological parameters like age (P=0.2681), T stage (P=0.2130), nodal status (P=0.3238) and lymph vascular invasion (LVI, P=0.5860) in patients with MIBC. A high expression of IL-22RA1 was associated with a shorter OS (P=0.0040) and disease-specific survival (P=0.0385). Furthermore, a shorter disease-free survival (DFS) was also associated with a high expression of IL-22RA1 (P=0.0102). In the multivariable analysis, IL-22RA1 expression was an independent prognostic predictors regarding OS (P=0.0096, HR=0.48). In the TCGA cohort, IL-22RA1 expression was independent regarding to OS and DFS. CONCLUSION: A high IL-22RA1 gene expression was associated with worse outcome. Furthermore, IL-22RA1 represented an independent predictor regarding OS in our cohort and therefore might be used for risk stratification in patients with MIBC.

5.
Eur Urol Focus ; 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33840611

RESUMO

CONTEXT: Holmium (HoLEP) and thulium laser enucleation of the prostate (ThuLEP) are the two methods most commonly applied for endoscopic enucleation of the prostate. It remains unclear which of the two is superior in terms of outcome and complications. OBJECTIVE: To compare perioperative and functional outcomes between HoLEP and ThuLEP. EVIDENCE ACQUISITION: A systematic review and meta-analysis were performed according to the recommendations of the Cochrane Collaboration and in line with the PRISMA criteria. A comprehensive database search including MEDLINE, Web of Science, CINAHL, ClinicalTrials.gov, and CENTRAL was conducted according to the PICO criteria. Only randomized controlled trials (RCTs) were considered. All review steps were conducted by two independent reviewers. Risk of bias was assessed using the revised Cochrane tool for RCTs. EVIDENCE SYNTHESIS: The search identified 556 studies, of which four were eligible for qualitative and quantitative analysis, reporting on a total of 579 patients with follow-up of up to 18 months. No significant differences in operating time, enucleation weight, catheterization time, or hospital stay were observed between ThuLEP and HoLEP. The decrease in hemoglobin was significantly lower for ThuLEP (mean difference -0.54 g/dl, 95% confidence interval [CI] -0.93 to -0.15; p < 0.001), but with low certainty of evidence. Transient urinary incontinence was more common for HoLEP (odds ratio 0.56, 95% CI 0.32-0.99; p = 0.045), again with low certainty of evidence. Furthermore, no significant differences were observed for other complications or for functional measures and symptom scores. CONCLUSIONS: ThuLEP and HoLEP offer comparable improvement in symptoms and postoperative voiding parameters. Both procedures are safe and major complications are rare. ThuLEP showed minor advantages for blood loss and the incidence of transient incontinence. This should be interpreted with caution owing to the low certainty of evidence. Therefore, treatment choice should be based on surgeon expertise and local conditions. PATIENT SUMMARY: We reviewed four clinical trials that compared holmium and thulium lasers for treatment to reduce the size of the prostate gland. Our review assessed outcomes and complications. We found that both laser techniques are safe and suitable for reducing symptoms due to an enlarged prostate. Blood loss and short-lasting urinary incontinence were slightly lower after thulium compared to holmium laser treatment.

6.
Int J Mol Sci ; 22(8)2021 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-33919527

RESUMO

BACKGROUND: Perioperative cisplatin-based chemotherapy (CBC) can improve the outcome of patients with muscle-invasive bladder cancer (MIBC), but it is still to be defined which patients benefit. Mutations in DNA damage response genes (DDRG) can predict the response to CBC. The value of DDRG expression as a marker of CBC treatment effect remains unclear. MATERIAL AND METHODS: RNA expression of the nine key DDRG (BCL2, BRCA1, BRCA2, ERCC2, ERCC6, FOXM1, RAD50, RAD51, and RAD52) was assessed by qRT-PCR in a cohort of 61 MICB patients (median age 66 y, 48 males, 13 females) who underwent radical cystectomy in a tertiary care center. The results were validated in the The Cancer Genome Atlas (TCGA) cohort of MIBC (n = 383). Gene expression was correlated with disease-free survival (DFS) and overall survival (OS). Subgroup analyses were performed in patients who received adjuvant cisplatin-based chemotherapy (ACBC) (Mannheim n = 20 and TCGA n = 75). RESULTS: Low expression of RAD52 was associated with low DFS in both the Mannheim and the TCGA cohorts (Mannheim: p = 0.039; TCGA: p = 0.017). This was especially apparent in subgroups treated with ACBC (Mannheim: p = 0.0059; TCGA: p = 0.012). Several other genes showed an influence on DFS in the Mannheim cohort (BRCA2, ERCC2, FOXM1) where low expression was associated with poor DFS (p < 0.05 for all). This finding was not fully supported by the data in the TCGA cohort, where high expression of FOXM1 and BRCA2 correlated with poor DFS. CONCLUSION: Low expression of RAD52 correlated with decreased DFS in the Mannheim and the TCGA cohort. This effect was especially pronounced in the subset of patients who received ACBC, making it a promising indicator for response to ACBC on the level of gene expression.


Assuntos
Antineoplásicos/uso terapêutico , Cisplatino/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína BRCA1/genética , Proteína BRCA1/metabolismo , Proteína BRCA2/genética , Proteína BRCA2/metabolismo , Biomarcadores Tumorais , Quimioterapia Adjuvante , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/genética , Feminino , Proteína Forkhead Box M1/genética , Proteína Forkhead Box M1/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/prevenção & controle , Neoplasias da Bexiga Urinária/genética
7.
Z Evid Fortbild Qual Gesundhwes ; 162: 63-69, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33824094

RESUMO

INTRODUCTION: Scientific evidence in medicine is based on data generated from research. Recently, the number of scientifically active physicians has decreased, which has led to the development of the Clinician Scientist Programs. To better structure and focus the research of young physicians, we aimed to investigate the impact of collaborations and other factors on the quality and output of scientific publications. METHODS: The abstracts of three annual congresses of the German Society of Urology were systematically analysed regarding content, collaborations, and study design. Full-text publications and journals were identified through a MEDLINE® search. Impact factors (IFs) were identified using Journal Citation Reports™. To identify factors which predict publication and IFs, χ2 and Wilcoxon rank-sum tests were used. Uni- and multivariable logistic regression analyses were performed to assess the best model for publication success for an abstract as well as the achievement of a high IF. RESULTS: 1,074 abstracts were reviewed. The publication rate of subsequent peer-reviewed full-text publications was 52.5%. Collaborations with at least one institution (odds ratio (OR) 2.02, 95% confidence interval (CI) 1.48-2.76, p <0.0001), statistical analysis (OR 1.92, 95% CI 1.41-2.60, p <0.0001), study design (prospective vs. retrospective: OR 1.43, 95% CI 1.06-1.93, p=0.021), and national collaborations (OR 1.43, 95% CI 1.04-1.98, p=0.029) increased the likelihood of publication in a peer-reviewed journal in a multivariable logistic regression analysis. Experimental design (OR 2.77, 95% CI 1.32-5.84, p=0.007), international collaborations (OR 2.26, 95% CI 1.23-4.15, p=0.009), oncologic topics (OR 1.94, 95% CI 1.23-3.07, p=0.005), prostate disease (OR 1.75, 95% CI 1.08-2.84, p=0.023), and statistical analysis (OR 1.68, 95% CI 1.06-2.64, p=0.026) were associated with a higher IF. CONCLUSION: Abstracts resulting from collaborative research projects had a higher likelihood of subsequent full-text publication and a higher IF. More full-text publications were reported when abstracts included a statistical analysis. Hence, intensive networking (e. g. at congresses and workshops) of researching physicians as well as statistical/biometrical classes could be key factors to improve academic success.


Assuntos
Sucesso Acadêmico , Médicos , Indexação e Redação de Resumos , Alemanha , Humanos , Masculino , Estudos Prospectivos , Editoração , Estudos Retrospectivos , Sociedades Médicas
8.
World J Urol ; 39(10): 3747-3754, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33881557

RESUMO

PURPOSE: Due to the tissue preserving approach of focal therapy (FT), local cancer relapse can occur. Uncertainty exists regarding triggers and outcome of salvage strategies. METHODS: Patients with biopsy-proven prostate cancer (PCa) after FT for localized PCa from 2011 to 2020 at eight tertiary referral hospitals in Germany that underwent salvage radical prostatectomy (S-RP), salvage radiotherapy (S-RT) or active surveillance (AS) were reported. Prostate specific antigen (PSA) changes, suspicious lesions on mpMRI and histopathological findings on biopsy were analyzed. A multivariable regression model was created for adverse pathological findings (APF) at S-RP specimen. Kaplan-Meier curves were generated to determine oncological outcomes. RESULTS: A total of 90 men were included. Cancer relapse after FT was detected at a median of 12 months (IQR 9-16). Of 50 men initially under AS 13 received S-RP or S-RT. In total, 44 men underwent S-RP and 13 S-RT. At cancer relapse 17 men (38.6%) in the S-RP group [S-RT n = 4 (30.8%); AS n = 3 (6%)] had ISUP > 2. APF (pT ≥ 3, ISUP ≥ 3, pN + or R1) were observed in 23 men (52.3%). A higher ISUP on biopsy was associated with APF [p = 0.006 (HR 2.32, 97.5% CI 1.35-4.59)] on univariable analysis. Progression-free survival was 80.4% after S-RP and 100% after S-RT at 3 years. Secondary therapy-free survival was 41.7% at 3 years in men undergoing AS. Metastasis-free survival was 80% at 5 years for the whole cohort. CONCLUSION: With early detection of cancer relapse after FT S-RP and S-RT provide sufficient oncologic control at short to intermediate follow-up. After AS, a high secondary-therapy rate was observed.

9.
Urolithiasis ; 49(3): 269-279, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33388823

RESUMO

The Clavien-Dindo Classification (CDC) lacks a combined score of multiple complications in one patient. The comprehensive complication index (CCI) circumvents this problem making it a valuable instrument to optimize quality control. We aimed to introduce and validate CCI in the treatment of urolithiasis. 60 day postoperative complications of 327 consecutive patients undergoing percutaneous nephrolitholapaxy (PNL) and ureterorenoscopy (URS) between 2017 and 2019 were retrospectively assessed and graded according to CDC. CCI was calculated for each patient. Overall morbidity scores of CCI and CDC were compared. Correlation analyses between the two scores and length of hospital stay (LOS) were performed. A multivariate analysis was performed to identify predictive factors for complications. Sample size calculation for an imaginary clinical trial was compared between CCI and CDC. A significant difference in overall morbidity between CCI and CDC was revealed for PNL (p < 0.001) and URS (p = 0.001). There was no statistically significant difference in comparing correlations between cumulative CCI and LOS versus non-cumulative CDC and LOS for both cohorts. Operating time > 90 min, maximum stone size, positive preoperative urine culture and PNL type (p < 0.001) were predictive factors for postoperative complications in PNL, while urine culture (p = 0.02) was for URS. Sample size calculation based on CCI resulted in a significant reduction of required patients for PNL (- 48%) and URS (- 84%) compared to CDC. CCI could successfully be validated in endourological stone treatment with the advantage of assessing complications in their entirety compared to CDC. CCI can significantly reduce the required sample size in future clinical trials.


Assuntos
Litotripsia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Controle de Qualidade , Ureteroscopia/efeitos adversos , Urolitíase/cirurgia , Adulto , Idoso , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Litotripsia/métodos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Resultado do Tratamento
10.
J Endourol ; 35(4): 444-450, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32935562

RESUMO

Purpose: Focal therapy (FT) became a frequently discussed treatment strategy of localized prostate cancer (PCa), but the acceptance and evaluation of FT by practicing urologists are still unclear. Methods: A 25-item anonymized online questionnaire (SurveyMonkey®) was compiled by the German Society of Residents in Urology Academics Prostate Cancer Working Group and sent to the members of the German association of Urology. Logistic regression analysis was performed to determine parameters for suggestion FT. Results: Two hundred ten urologists (median age 49 years) participated, from which 72% stated PCa as their main treatment focus. Ninety-nine percent of urologists were aware of and 54% wanted to improve their knowledge about FT. Sixty-five percent do not treat PCa with FT. FT is seen as an alternative to active surveillance and radiotherapy/radical prostatectomy by 66% and 37%, respectively. Regarding FT treatment strategies, 35% and 45% would treat all or all significant PCa foci, respectively, whereas 19% would treat mainly the index foci. Currently, 27% believe that FT will be an option as standard treatment in future, but 48% would not suggest FT to their patients, owing to an absence of evidence and insufficient diagnostic tools for proper patient selection today. Suggesting FT to patients is associated with self-performing FT (odds ratio [OR] 2.88, 95% confidence interval [CI] 1.31-6.31) and believing in FT as a standard treatment in future (OR 9.05, 95% CI 6.68-22.30) (both p < 0.01). Conclusion: FT has currently no wide acceptance in German practicing urologists, mainly attributable to an absence of evidence for FT superiority compared to standard treatments.


Assuntos
Neoplasias da Próstata , Urologistas , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Prostatectomia , Neoplasias da Próstata/cirurgia
11.
World J Urol ; 39(4): 1121-1129, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32533247

RESUMO

PURPOSE: Focal therapies (FTs) are investigated within prospective studies on selected patients treated for localized prostate cancer (PCa). Benefits are preservation of genitourinary function and reduced complications, but follow-up is elaborate and is associated with uncertainty as cancer-free survival appears to be lower compared to standard radical treatments. The aim of this study was to analyse patient-reported acceptance of FT and evaluate factors associated with treatment decision regret. METHODS: 52 patients who received focal high-intensity focused ultrasound for low- to intermediate-risk PCa between 2014 and 2019 within two prospective trials were eligible for a survey regarding PCa-related treatment regret and quality-of-life (Clark's scale) and the following potential predictors: sociodemographic variables, Charlson Comorbidity Index, subjective aging (AARC-10 SF), and general health-related quality-of-life (SF-12). Cancer persistence/recurrence (multiparametric MRI and fusion biopsy after 12 months) and functional outcomes (EPIC-26 UI/UIO/S) data were also included in this study. RESULTS: The overall survey response rate was 92.3% (48/52 patients). Median follow-up was 38 months (interquartile range = 25-50 months). In total, ten patients (20.8%) reported treatment decision regret. In univariable analyses, a clinically meaningful increase in urinary incontinence showed a significant association (OR 4.43; 95% CI 0.99-20.53; p = 0.049) with regret. Cancer recurrence (OR 12.31; 95% CI 1.78-159.26; p = 0.023) and general health worry as a domain of Clark's scale (OR 1.07; 95% CI 1.03-1.14; p < 0.01) were predictors of regret in a multivariable logistic regression model (AUC = 0.892). CONCLUSION: Acceptance of FT is comparable to standard treatments. Extensive follow-up including regular PSA testing does not cause additional regret but careful patient selection and information before FT is crucial.

12.
J Endourol ; 35(4): 490-496, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33222525

RESUMO

Purpose: To evaluate the Comprehensive Complication Index (CCI) for reporting complications in lower urinary tract transurethral procedures and compare it with the Clavien-Dindo classification (CDC). Materials and Methods: A total of 450 consecutive patients were included into the analyses [150 each of transurethral resection of bladder tumors (TURBT), transurethral resection of the prostate (TURP), and transurethral enucleation of the prostate using Tm:YAG, (ThuLEP)]. Complications were assessed according to the modified CDC. The CCI was calculated using a freely accessible online tool. Descriptive statistics and correlation analyses were applied to quantify operational differences and length of stay (LOS) between CDC and CCI. Sample size calculations for hypothetical clinical trials were contrasted for CDC and CCI application. Results: Overall n = 150 patients with complications (33.3%) within the first 60 days after operation were identified. Of these, n = 125 (83.4%) were minor complications up to CDC grade IIIa. Of patients with complications, n = 57 patients (12.6%) experienced more than one complication. Here, the cumulative CCI led to an upgrade of at least one CDC grade in 33 patients. Hence, in 22.0% of cases, the highest CDC grade underestimated the degree of complications. CCI showed higher correlation with LOS compared with CDC (all r > 0.2, all p-values ≤0.0001). Using CCI instead of CDC for sample calculation resulted in a strong reduction of the required number of patients for all three interventions (percentage of patient number decrease: -93.2% for TURBT, -71.8% for TURP, and -81.1% for ThuLEP). Conclusion: The CCI gives a more precise interpretation of the postinterventional complications of TURBT, TURP, and ThuLEP. CCI application may reduce the required sample size for clinical trials and will relieve their recruitment in the future.


Assuntos
Ressecção Transuretral da Próstata , Sistema Urinário , Cistectomia , Humanos , Masculino , Complicações Pós-Operatórias/etiologia , Índice de Gravidade de Doença
13.
Cancers (Basel) ; 12(7)2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32630787

RESUMO

Radiomics is an emerging field of image analysis with potential applications in patient risk stratification. This study developed and evaluated machine learning models using quantitative radiomic features extracted from multiparametric magnetic resonance imaging (mpMRI) to detect and classify prostate cancer (PCa). In total, 191 patients that underwent prostatic mpMRI and combined targeted and systematic fusion biopsy were retrospectively included. Segmentations of the whole prostate glands and index lesions were performed manually in apparent diffusion coefficient (ADC) maps and T2-weighted MRI. Radiomic features were extracted from regions corresponding to the whole prostate gland and index lesion. The best performing combination of feature setup and classifier was selected to compare its predictive ability of the radiologist's evaluation (PI-RADS), mean ADC, prostate specific antigen density (PSAD) and digital rectal examination (DRE) using receiver operating characteristic (ROC) analysis. Models were evaluated using repeated 5-fold cross-validation and a separate independent test cohort. In the test cohort, an ensemble model combining a radiomics model, with models for PI-RADS, PSAD and DRE achieved high predictive AUCs for the differentiation of (i) malignant from benign prostatic lesions (AUC = 0.889) and of (ii) clinically significant (csPCa) from clinically insignificant PCa (cisPCa) (AUC = 0.844). Our combined model was numerically superior to PI-RADS for cancer detection (AUC = 0.779; p = 0.054) as well as for clinical significance prediction (AUC = 0.688; p = 0.209) and showed a significantly better performance compared to mADC for csPCa prediction (AUC = 0.571; p = 0.022). In our study, radiomics accurately characterizes prostatic index lesions and shows performance comparable to radiologists for PCa characterization. Quantitative image data represent a potential biomarker, which, when combined with PI-RADS, PSAD and DRE, predicts csPCa more accurately than mADC. Prognostic machine learning models could assist in csPCa detection and patient selection for MRI-guided biopsy.

14.
Int J Mol Sci ; 21(12)2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32575490

RESUMO

Current outcome prediction markers for localized prostate cancer (PCa) are insufficient. The impact of the lipid-modifying Sphingomyelin Phosphodiesterase Acid Like 3B (SMPDL3B) in PCa is unknown. Two cohorts of patients with PCa who underwent radical prostatectomy (n = 40, n = 56) and benign prostate hyperplasia (BPH) controls (n = 8, n = 11) were profiled for SMPDL3B expression with qRT-PCR. Publicly available PCa cohorts (Memorial Sloane Kettering Cancer Centre (MSKCC; n = 131, n = 29 controls) and The Cancer Genome Atlas (TCGA; n = 497, n = 53 controls)) served for validation. SMPDL3B's impact on proliferation and migration was analyzed in PC3 cells by siRNA knockdown. In both cohorts, a Gleason score and T stage independent significant overexpression of SMPDL3B was seen in PCa compared to BPH (p < 0.001 each). A lower expression of SMPDL3B was associated with a shorter overall survival (OS) (p = 0.005) in long term follow-up. A SMPDL3B overexpression in PCa tissue was confirmed in the validation cohorts (p < 0.001 each). In the TCGA patients with low SMPDL3B expression, biochemical recurrence-free survival (p = 0.011) and progression-free interval (p < 0.001) were shorter. Knockdown of SMPDL3B impaired PC3 cell migration but not proliferation (p = 0.0081). In summary, SMPLD3B is highly overexpressed in PCa tissue, is inversely associated with localized PCa prognosis, and impairs PCa cell migration.


Assuntos
Biomarcadores Tumorais/genética , Regulação para Baixo , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Esfingomielina Fosfodiesterase/genética , Estudos de Casos e Controles , Movimento Celular , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Gradação de Tumores , Estadiamento de Neoplasias , Células PC-3 , Prognóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Análise de Sobrevida , Resultado do Tratamento
15.
Urol Int ; 104(5-6): 378-385, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32396911

RESUMO

INTRODUCTION: Urinary tract infections (UTI) represent the most frequent complications after transrectal focal ablation of prostate cancer. Single-shot antibiotic prophylaxis for prevention has not yet been described. METHODS: In this cohort study of patients who received a high-intensity focused ultrasound (HIFU) ablation of prostate cancer within a registered prospective single-arm trial, we analyzed posttreatment UTI (≤30 days after HIFU) related to perioperative antibiotic management in an exploratory analysis: single-shot prophylaxis or targeted treatment for bacteriuria. Potential risk factors associated with UTI were evaluated by uni- and multivariate regression analyses. RESULTS: In total, 55 patients were eligible for analysis. Of these, 76.4% received antibiotic single-shot prophylaxis. UTI occurred in 10.7% of all patients, 5.4% developed fever, 3.6% required hospitalization. An antibiotic single-shot prophylaxis helped to protect 90.5% of men from infectious complications. Estimated effects indicate that a longer posttreatment catheterization (OR 3.38, 95% CI 0.47-27.08) and larger ablation volume (OR 4.85, 95% CI 0.61-107.49) might be associated with the highest risk for UTI after treatment. CONCLUSION: Single-shot antibiotic prophylaxis compared to a targeted antibiotic treatment showed a similar effectivity to prevent patients from infectious complications and should be considered as an element of antibiotic stewardship. Further research on risk factors and antibiotic strategies is required.


Assuntos
Antibacterianos/administração & dosagem , Antibioticoprofilaxia/métodos , Complicações Pós-Operatórias/prevenção & controle , Neoplasias da Próstata/cirurgia , Ultrassom Focalizado Transretal de Alta Intensidade , Infecções Urinárias/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Estudos de Viabilidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reto
16.
Eur Urol Focus ; 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33877047

RESUMO

BACKGROUND: Focal therapy (FT) with its favorable side-effect profile represents an option between active surveillance and traditional whole-gland treatment in localized prostate cancer (PCa). Consensus statements recommend eligibility criteria based on magnetic resonance imaging (MRI)-targeted and systematic combination biopsy. OBJECTIVE: To estimate the future potential of FT by analyzing the number of men eligible for FT among all men with biopsy-proven PCa and to judge the potential of different energy sources. DESIGN, SETTING, AND PARTICIPANTS: Consensus criteria on FT were analyzed. Patients with biopsy-proven PCa from six tertiary referral hospitals and one outpatient practice in Germany had received a software-based combination biopsy. Men with Prostate Imaging Reporting and Data System (PI-RADS) ≥3 lesions based on PI-RADS v2 were included. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patients were analyzed for potential treatment by FT and hemiablation. MRI lesions were mapped according to prostatic zones. RESULTS AND LIMITATIONS: In total, 2371 patients were analyzed. According to consensus criteria (biopsy-proven unifocal lesion of International Society of Urological Pathology [ISUP] grade group ≤2, prostate-specific antigen [PSA] ≤15ng/mL, and life expectancy >10yr), 303 patients (12.8%; ISUP 1: n=148 [6.2%]; ISUP 2: n=155 [6.5%]) were potential candidates for FT. A maximum PSA level of <10ng/mL would exclude further 60 (2.5%) of these men. The eligibility for hemiablation is slightly higher (16.2%). Unifocal lesions (n=288) were equally distributed within the prostate (anteriorly [31%], apically [29%], and dorsally [36%]). CONCLUSIONS: With adherence to consensus statements, only a minority of PCa patients present as potential candidates for FT. Distribution of tumor localization suggests the need for different energy modalities to warrant an optimal FT treatment. PATIENT SUMMARY: We analyzed how many men who receive a magnetic resonance imaging-targeted and systematic prostate biopsy are candidates for the experimental focal therapy of the prostate. When following expert recommendations, only a small number of men are potential candidates for this alternative treatment.

17.
Urol Oncol ; 37(10): 678-687, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31375340

RESUMO

OBJECTIVES: To assess if a multiparametric magnetic resonance imaging (mpMRI)-targeted biopsy (TB) strategy is precise enough to replace systematic biopsies (SB) among men with different biopsy indications since an imaging-based pathway to guide indication and targeted prostate biopsy is currently under debate. MATERIALS AND METHODS: Retrospective analysis was performed of 594 patients with one or more lesions according to Prostate Imaging and Reporting Data System (PI-RADS) receiving a consecutive TB and SB for one of the 3 indications: primary cancer suspicion (51.7%), persistent cancer suspicion after prior negative biopsy (35.4%), or control of a confirmed cancer (12.9%). Detection rates for overall cancer (CaP) and clinically significant cancer (csCaP, Gleason Score ≥3+4) were compared between TB and SB and to a combined approach for all patients and within the subgroups. Characteristics of cancers missed by one biopsy strategy were analyzed. RESULTS: TB detected less CaP (302 vs. 366, P < 0.001) and csCaP (204 vs. 210 patients, P = 0.409) compared to SB except for men with prior negative biopsies (65 vs. 64 csCaP, P = 0.363). Cancer detection by TB or SB was independent of cancer localization and imaging characteristics. Combined TB and SB outperformed the single approaches for CaP and csCaP detection in each subgroup. CONCLUSIONS: A single mpMRI and TB approach leads to a substantial number of missed CaP and csCaP across biopsies with different indications. Ongoing improvements of imaging, reading standardization, and biopsy techniques are required before replacing SB.


Assuntos
Biópsia Guiada por Imagem/métodos , Imagem por Ressonância Magnética Intervencionista/métodos , Próstata/cirurgia , Neoplasias da Próstata/cirurgia , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Próstata/patologia , Neoplasias da Próstata/patologia , Estudos Retrospectivos
18.
Sci Rep ; 9(1): 3048, 2019 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-30816191

RESUMO

Avoiding hyperthermia entails considerable metabolic costs for endotherms. Such costs increase in warm conditions, when endotherms may trade food intake for cooler areas to avoid heat stress and maximize their energy balance. The need to reduce heat stress may involve the adoption of tactics affecting space use and foraging behaviour, which are important to understand and predict the effects of climate change and inform conservation. We used resource selection models to examine the behavioural response to heat stress in the Alpine ibex (Capra ibex), a cold-adapted endotherm particularly prone to overheating. Ibex avoided heat stress by selecting the space based on the maximum daily temperature rather than moving hourly to 'surf the heat wave', which minimised movement costs but prevented optimal foraging. By integrating these findings with new climate forecasts, we predict that rising temperatures will force mountain ungulates to move upward and overcrowd thermal refugia with reduced carrying capacity. Our approach helps in identifying priority areas for the conservation of mountain species.


Assuntos
Migração Animal/fisiologia , Animais Selvagens/fisiologia , Aquecimento Global , Resposta ao Choque Térmico/fisiologia , Ruminantes/fisiologia , Aclimatação/fisiologia , Animais , Conservação dos Recursos Naturais , Monitorização de Parâmetros Ecológicos/estatística & dados numéricos , Metabolismo Energético/fisiologia , Previsões , Temperatura Alta , Locomoção/fisiologia , Masculino , Estações do Ano , Análise Espaço-Temporal
19.
Clin Genitourin Cancer ; 17(2): 145-153.e5, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30709785

RESUMO

BACKGROUND: Prostate cancer with neuroendocrine differentiation (NEPCA) shares similarities in tumor biology with small-cell lung cancer. While immunotherapies were successfully tested in small-cell lung cancer, and programmed death ligand 1 (PD-L1) expression arises as an essential predictive biomarker, the local immune status in NEPCA is still poorly described. PATIENTS AND METHODS: Paraffin-embedded tissue samples of 39 patients (7 adenocarcinomas with neuroendocrine differentiation [ACA NED], 20 small-cell neuroendocrine carcinomas, 2 well-differentiated neuroendocrine tumors of NEPCA, and 10 adenocarcinoma liver metastases) were examined retrospectively by immunohistochemistry of chromogranin A (CGA), CD56, synaptophysin (SYN), CD3, and PD-L1. Laser capture microdissection was used for neuroendocrine hot-spot evaluation for additional real-time reverse transcription-quantitative PCR analysis (PD-L1, CGA, CD56, SYN, GRP, ASCL1, and DLK1). RESULTS: PD-L1 immunohistochemistry expression in NEPCA was observed by assay E1L3N in 5 (20.8%) of 24 samples, but not by assay 22c3. Gene expression of PD-L1 could be evaluated in 18 (62%) of 29 samples. Nine (69%) of 13 prostate specimens and 2 (40%) of 5 liver metastases were positive for PD-L1. In ACA NED 4 (80%) of 5 and in small-cell neuroendocrine carcinomas 6 (50%) of 12 specimens were positive for PD-L1. Tumor-infiltrating lymphocytes ≥ 10% were observed in 9 (37.5%) of 24 specimens. Low ASCL1 expression was observed in liver metastases. CONCLUSION: These data identify molecular PD-L1 features in NEPCA. The predictive role of PD-L1 status and tumor-infiltrating lymphocytes in NEPCA remains to be established.


Assuntos
Antígeno B7-H1/genética , Neoplasias Hepáticas/imunologia , Linfócitos do Interstício Tumoral/imunologia , Tumores Neuroendócrinos/imunologia , Neoplasias da Próstata/genética , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Microdissecção e Captura a Laser , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/genética , Prognóstico , Neoplasias da Próstata/imunologia , Estudos Retrospectivos
20.
Sci Rep ; 9(1): 2334, 2019 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-30787370

RESUMO

Although it is well known that mean annual rainfall (MAR) and rainfall seasonality have a key role in influencing the distribution of tree and grass cover in African tropical grassy biomes (TGBs), the impact of intra-seasonal rainfall variability on these distributions is less agreed upon. Since the prevalent mechanisms determining biome occurrence and distribution change with MAR, this research investigates the role of intra-seasonal rainfall variability for three different MAR ranges, assessing satellite data on grass and tree cover, rainfall and fire intervals at a sub-continental scale in sub-Saharan Africa. For MAR below 630 mm y-1, rainfall frequency had a positive relationship with grass cover; this relationship however became mostly negative at intermediate MAR (630-1200 mm y-1), where tree cover correspondingly mostly increased with rainfall frequency. In humid TGBs, tree cover decreased with rainfall intensity. Overall, intra-seasonal rainfall variability plays a role in determining vegetation cover, especially in mesic TGBs, where the relative dominance of trees and grasses has previously been largely unexplained. Importantly, the direction of the effect of intra-seasonal variability changes with MAR. Given the predicted increases in rainfall intensity in Africa as a consequence of climate change, the effects on TGBs are thus likely to vary depending on the MAR levels.


Assuntos
Ecossistema , Poaceae/fisiologia , Chuva , Estações do Ano , Árvores/fisiologia , Clima Tropical , África ao Sul do Saara , Modelos Lineares
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