Preoperative fibrinogen/CRP score predicts survival in upper urothelial tract carcinoma patients undergoing radical curative surgery

Purpose Upper tract urothelial carcinoma (UTUC) represents an often aggressive malignancy associated with poor prognosis. Therefore, finding reliable prognostic biomarkers in patients undergoing curative surgery for improved risk stratification is crucial. We evaluated the prognostic value of the Fibrinogen/C-reactive protein (FC)-score in a cohort of surgically treated UTUC patients. Methods 170 patients with radiologically and histologically verified UTUC who underwent radical curative surgery between 1990 and 2020, were included. The FC-score was calculated for each patient, with patients receiving 1 point each if Fibrinogen and/or CRP levels were elevated above the 25th or 75th percentile, respectively. Patients were divided into three subgroups according to their FC-score of 0, 1 or 2 point(s). Kaplan–Meier analysis, uni- and multivariable Cox proportional hazard models were implemented. We determined cancer-specific survival (CSS) as primary endpoint, whereas overall survival (OS) and recurrence-free survival (RFS) were considered secondary endpoints. Results High FC-score (2 points) was significantly associated with adverse histological features such as vascular invasion (OR = 4.08, 95%CI 1.18–14.15, p = .0027) and tumour necrosis (OR = 6.67, 95%CI 1.35–32.96, p = 0.020). Both, uni- and multivariable Cox proportional hazard models showed the FC-score as a significant predictor for CSS (univariable analysis: FC-score = 1: HR = 1.90, 95%CI 0.92–3.93, p = 0.085 | FC-score = 2: HR = 2.86, 95%CI 1.22–6.72, p = 0.016). Furthermore, in univariable analysis, patients with higher FC-score had significantly shorter OS (FC-score = 1: HR = 1.32, 95%CI 0.70–2.49, p = 0.387 | FC-score = 2: HR = 2.19, 95%CI 1.02–4.67, p = 0.043). However, this did not prevail in multivariable analysis. Conclusion The FC-score represents a novel potential biomarker in patients with UTUC undergoing radical curative surgery

Prognostic significance of pathologic lymph node invasion in metastatic renal cell carcinoma in the immunotherapy era

Background This study aimed to test the prognostic significance of pathologically confirmed lymph node invasion in metastatic renal cell carcinoma (mRCC) patients in this immunotherapy era. Methods Surgically treated mRCC patients were identified in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2018. Kaplan-Meier plots and multivariable Cox-regression models were fitted to test for differences in cancer-specific mortality (CSM) and overall mortality (OM) according to N stage (pN0 vs pN1 vs. pNx). Subgroup analyses addressing pN1 patients tested for CSM and OM differences according to postoperative systemic therapy status. Results Overall, 3149 surgically treated mRCC patients were identified. Of these patients, 443 (14%) were labeled as pN1, 812 (26%) as pN0, and 1894 (60%) as pNx. In Kaplan-Meier analyses, the median CSM-free survival was 15 months for pN1 versus 40 months for pN0 versus 35 months for pNx (P < 0.001). In multivariable Cox regression analyses, pN1 independently predicted higher CSM (hazard ratio [HR], 1.88; P < 0.01) and OM (HR, 1.95; P < 0.01) relative to pN0. In sensitivity analyses addressing pN1 patients, postoperative systemic therapy use independently predicted lower CSM (HR, 0.73; P < 0.01) and OM (HR, 0.71; P < 0.01). Conclusion Pathologically confirmed lymph node invasion independently predicted higher CSM and OM for surgically treated mRCC patients. For pN1 mRCC patients, use of postoperative systemic therapy was associated with lower CSM and OM. Consequently, N stage should be considered for individual patient counseling and clinical decision-making

Patterns of peripheral blood B-cell subtypes are associated with treatment response in patients treated with immune checkpoint inhibitors: a prospective longitudinal pan-cancer study

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized systemic anti-tumor treatments across different types of cancer. Nevertheless, predictive biomarkers regarding treatment response are not routinely established yet. Apart from T-lymphocytes, the humoral immunity of B-lymphocytes is studied to a substantially lesser extent in the respective setting. Thus, the aim of this study was to evaluate peripheral blood B-cell subtypes as potential predictors of ICI treatment response. METHODS: Thirty-nine cancer patients receiving ICI therapy were included into this prospective single-center cohort study. All had a first blood draw at the date before treatment initiation and a second at the time of first response evaluation (after 8-12 weeks). Seven different B-cell subtypes were quantified by fluorescence-activated cell sorting (FACS). Disease control- (DCR) and objective response rate (ORR) were co-primary study endpoints. RESULTS: Overall, DCR was 48.7% and ORR was 25.6%, respectively. At baseline, there was no significant association of any B-cell subtype with neither DCR nor ORR. At the first response evaluation, an increase in the frequency of CD21(-) B-cells was a statistically significant negative predictor of response, both regarding DCR (OR=0.05, 95%CI=0.00-0.67, p=0.024) and ORR (OR=0.09, 95%CI=0.01-0.96, p=0.046). An increase of the frequency of switched memory B-cells was significantly associated with reduced odds for DCR (OR=0.06, 95%CI=0.01-0.70, p=0.025). Patients with an increased frequency of naïve B-cells were more likely to benefit from ICI therapy as indicated by an improved DCR (OR=12.31, 95%CI=1.13-134.22, p=0.039). CONCLUSION: In this study, certain B-cell subpopulations were associated with ICI treatment response in various human cancer types

Regional differences in clear cell metastatic renal cell carcinoma patients across the USA

Purpose To test for regional differences in clear cell metastatic renal cell carcinoma (ccmRCC) patients across the USA. Methods The Surveillance, Epidemiology, and End Results (SEER) database (2000–2018) was used to tabulate patient (age at diagnosis, sex, race/ethnicity), tumor (N stage, sites of metastasis) and treatment characteristics (proportions of nephrectomy and systemic therapy), according to 12 SEER registries. Multinomial regression models, as well as multivariable Cox regression models, tested the overall mortality (OM) adjusting for those patient, tumor and treatment characteristics. Results In 9882 ccmRCC patients, registry-specific patient counts ranged from 4025 (41%) to 189 (2%). Differences across registries existed for sex (24–36% female), race/ethnicity (1–75% non-Caucasian), N stage (N1 25–35%, NX 3–13%), proportions of nephrectomy (44–63%) and systemic therapy (41–56%). Significant inter-registry differences remained after adjustment for proportions of nephrectomy (46–63%) and systemic therapy (35–56%). Unadjusted 5-year OM ranged from 73 to 85%. In multivariable analyses, three registries exhibited significantly higher OM (SEER registry 5: hazard ratio (HR) 1.20, p = 0.0001; SEER registry 7:HR 1.15, p = 0.008M SEER registry 10: HR 1.15, p = 0.04), relative to the largest reference registry (n = 4025). Conclusion Important regional differences including patient, tumor and treatment characteristics exist, when ccmRCC patients included in the SEER database are studied. Even after adjustment for these characteristics, important OM differences persisted, which may require more detailed analyses to further investigate these unexpected differences

Combining targeted and systematic prostate biopsy improves prostate cancer detection and correlation with the whole mount histopathology in biopsy naïve and previous negative biopsy patients

OBJECTIVE: Guidelines for previous negative biopsy (PNB) cohorts with a suspicion of prostate cancer (PCa) after positive multiparametric (mp) magnetic-resonance-imaging (MRI) often favour the fusion-guided targeted prostate-biopsy (TB) only approach for Prostate Imaging-Reporting and Data System (PI-RADS) ≥3 lesions. However, recommendations lack direct biopsy performance comparison within biopsy naïve (BN) vs. PNB patients and its prognostication of the whole mount pathology report (WMPR), respectively. We suppose, that the combination of TB and concomitant TRUS-systematic biopsy (SB) improves the PCa detection rate of PI-RADS 2, 3, 4 or 5 lesions and the International Society of Urological Pathology (ISUP)-grade predictability of the WMPR in BN- and PNB patients. METHODS: Patients with suspicious mpMRI, elevated prostate-specific-antigen and/or abnormal digital rectal examination were included. All PI-RADS reports were intramurally reviewed for biopsy planning. We compared the PI-RADS score substratified TB, SB or combined approach (TB/SB) associated BN- and PNB-PCa detection rate. Furthermore, we assessed the ISUP-grade variability between biopsy cores and the WMPR. RESULTS: According to BN (n = 499) vs. PNB (n = 314) patients, clinically significant (cs) PCa was detected more frequently by the TB/SB approach (62 vs. 43%) than with the TB (54 vs. 34%) or SB (57 vs. 34%) (all p < 0.0001) alone. Furthermore, we observed that the TB/SB strategy detects a significantly higher number of csPCa within PI-RADS 3, 4 or 5 reports, both in BN and PNB men. In contrast, applied biopsy techniques were equally effective to detect csPCa within PI-RADS 2 lesions. In case of csPCa diagnosis the TB approach was more often false-negative in PNB patients (BN 11% vs. PNB 19%; p = 0.02). The TB/SB technique showed in general significantly less upgrading, whereas a higher agreement was only observed for the total and BN patient cohort. CONCLUSION: Despite csPCa is more frequently found in BN patients, the TB/SB method always detected a significantly higher number of csPCa within PI-RADS 3, 4 or 5 reports of our BN and PNB group. The TB/SB strategy predicts the ISUP-grade best in the total and BN cohort and in general shows the lowest upgrading rates, emphasizing its value not only in BN but also PNB patients

Transurethrale Holmiumlaser Enukleation der Prostata (HoLEP) versus Transurethrale Elektroresektion der Prostata (TURP)

Ziele: Trotz ihrer signifikanten Morbidität stellt die transurethrale Resektion der Prostata (TURP) den gold standard dar für die instrumentelle Therapie der durch die benigne Prostatahyperplasie (BPH) bedingten Blasenauslassobstruktion. Mit dem Hochleistungs-Holmium: YAG Laser kann endoskopisch, in einer relativ blutungsarmen Weise, Prostatagewebe enukleiert werden. Wir verglichen die Technik der transurethralen Holmium-Laser-Enukleation der Prostata (HoLEP) mit der Standard-TURP bei der operativen Therapie von Prostataadenomen. Wir präsentieren die perioperativen Daten, die Kurz- und Langzeitergebnisse dieser randomisierten klinischen Studie. Material und Methoden: Insgesamt wurden 200 Patienten mit einer urodynamisch nachgewiesenen benignen Prostataobstruktion bei einem Prostatavolumen kleiner 100g im transrektalen Ultraschall in ein TURP- und HoLEP-Kollektiv randomisiert. Alle Patienten wurden präoperativ und postoperativ nach 1,6, 12, 18, 24 und 36 Monaten durch Erhebung des American Urological Association symptom score und Messung der maximalen Harnflussrate und des Restharns evaluiert. Die perioperativen Daten und die postoperativen Ergebnisse wurden verglichen. Alle Komplikationen wurden vermerkt. Ergebnisse: Bei der HoLEP waren die Katheterzeit, der Krankenhausaufenthalt und der Hämoglobinverlust signifikant geringer, jedoch die Operationszeit signifikant länger als bei der TURP. HoLEP und TURP führten zu signifikanter und anhaltender Verbesserung aller Miktionsparameter, wobei der Restharn bis einschließlich 36 Monate postoperativ in der HoLEP Gruppe signifikant geringer blieb. Auch die perioperative Morbidität war bei der HoLEP kleiner; Kontinenz, Potenz und Spätkomplikation waren in beiden Gruppen ähnlich. Schlussfolgerungen: HoLEP ist mindestens genauso effektiv wie TURP. HoLEP dauert länger, jedoch sind die perioperative Morbidität, Katheter- und Krankenhausdauer geringer. Beide Methoden zeigen befriedigende Langzeitergebnisse mit wenigen Spätkomplikationen. Dies bestätigt die Dauerhaftigkeit des Therapieerfolges dieser 2. Verfahren.Purpose: Transurethral electrocautery resection (TURP) is generally regarded as the gold standard surgical treatment for bladder outflow obstruction due to benign prostatic hyperplasia (BPH) despite its rather high morbidity. The high powered holmium: YAG laser can be used endoscopically to enucleate prostatic tissue in a relatively bloodless manner. The technique of transurethral holmium laser enucleation of the prostate (HoLEP) was compared to standard TURP for the surgical management of prostate adenomas. We present the perioperative data, short and long-term results of this randomized clinical trial. Materials and Methods: A total of 200 patients with urodynamic obstruction with a prostate less than 100 gm on transrectal ultrasound were randomized into 2 comparable groups and assigned to HoLEP or TURP. All patients were assessed preoperatively and followed prospectively 1, 6, 12, 18, 24, and 36 months postoperatively with an American Urological Association symptom score, peak urinary flow rate and post-void residual measurement. Perioperative data and postoperative outcome were compared. All complications were noted. Results: HoLEP was significantly superior to TURP in terms of catheter time, hospital stay and hemoglobin loss but operative time was significantly longer. HoLEP and TURP resulted in a significant and lasting improvement of all parameters with post-void residual volume still significantly better in the HoLEP group at the 36-month assessment. Perioperative morbidity was less in the HoLEP group; continence, potency and late complications were similar in both groups. Conclusion: HoLEP is at least as effective as TURP. HoLEP takes longer than TURP, but perioperative morbidtity, catheter time and hospital stay is less. Both treatments have satisfactory long term results with a low late complication rate. This confirms the durability of these 2 procedures

Management of Anterior Urethral Strictures in Adults: A Survey of Contemporary Practice in Germany

Introduction: Treatment methods of anterior urethral strictures in adults have undergone considerable changes in the recent past. Our goal was to determine national practice patterns among German urologists and to compare results with the results of prior international surveys. Methods: We conducted a survey on the management of urethral strictures among German urologists. Results: Eight hundred forty-five urologists, representing about 14.6% of German urologists, answered the survey. Most common procedures were direct vision internal urethrotomy (DVIU; 87.2%), blind internal urethrotomy (57.5%), dilatation (56.3%), ventral buccal mucosa graft urethroplasty (31.6%) and excision and primary anastomosis (28.9%). In case of a 3.5-cm bulbar stricture and in the case of a 1-cm bulbar stricture after 2 failed DVIUs, a consecutive urethroplasty was significantly more often favoured compared to transurethral treatment options (44.9 vs. 21.3% and 59.4 vs. 8.3%, both p < 0.001). Conclusion: Open urethral reconstruction reveals to be a more common method in practice nowadays. Adherence to recommended treatment algorithms improved in comparison to prior surveys

Human Tularemia Epididymo-Orchitis Caused by Francisella tularensis Subspecies holartica, Austria

A previously healthy man in Austria had tularemia epididymo-orchitis develop, leading to unilateral orchiectomy. Francisella tularensis subspecies holartica was detected by 16S rRNA gene sequencing analysis of inflamed granulomatous testicular tissue. Clinicians should suspect F. tularensis as a rare etiologic microorganism in epididymo-orchitis patients with relevant risk factors

Management of Anterior Urethral Strictures in Adults: A Survey of Contemporary Practice in Germany

Introduction: Treatment methods of anterior urethral strictures in adults have undergone considerable changes in the recent past. Our goal was to determine national practice patterns among German urologists and to compare results with the results of prior international surveys. Methods: We conducted a survey on the management of urethral strictures among German urologists. Results: Eight hundred forty-five urologists, representing about 14.6% of German urologists, answered the survey. Most common procedures were direct vision internal urethrotomy (DVIU; 87.2%), blind internal urethrotomy (57.5%), dilatation (56.3%), ventral buccal mucosa graft urethroplasty (31.6%) and excision and primary anastomosis (28.9%). In case of a 3.5-cm bulbar stricture and in the case of a 1-cm bulbar stricture after 2 failed DVIUs, a consecutive urethroplasty was significantly more often favoured compared to transurethral treatment options (44.9 vs. 21.3% and 59.4 vs. 8.3%, both p < 0.001). Conclusion: Open urethral reconstruction reveals to be a more common method in practice nowadays. Adherence to recommended treatment algorithms improved in comparison to prior surveys