Functional Outcome and Safety of Endoscopic Treatment Options for Benign Prostatic Obstruction (BPO) in Patients ≥ 75 Years of Age.

Background: The selection of suitable patients for the surgical treatment of benign prostatic obstruction (BPO) is a challenge in persons ≥75 years of age. Methods: After a systematic literature search of PubMed, 22 articles were included in this review. Clinical and functional parameters were evaluated statistically. Results: The mean age of the patients was ≥79 years. The mean duration of postoperative catheterization ranged between 2 (d) (ThuLEP, thulium laser enucleation of the prostate) and 4.4 days (TURP, transurethral resection of the prostate). Complication rates ranged between 6% (HoLAP, holmium laser ablation of the prostate) and 34% (PVP, photoselective vaporization of the prostate); the maximum rate of severe complications was 4% (TURP). The mean postoperative maximal urinary flow (Qmax) in mL/sec. ranged between 12.9 mL/sec. (HoLAP) and 19.8 mL/sec (Hol-TUIP, holmium laser transurethral incision of the prostate). The mean quality of life (QoL) score fell from 4.7 ± 0.9 to 1.8 ± 0.7 (HoLEP), from 4.1 ± 0.4 to 1.9 ± 0.8 (PVP), from 5.1 ± 0.2 to 2.1 ± 0.2 (TURP), and from 4 to 1 (ThuVEP, thulium laser vapoenucleation of the prostate). Pearson's correlation coefficient (r) revealed a positive linear correlation between age and inferior functional outcome (higher postoperative International Prostate Symptom Score (IPSS) [r = 0.4175]), higher overall complication rates (r = 0.5432), and blood transfusions (r = 0.4474) across all surgical techniques. Conclusions: This meta-analysis provides the summary estimates for perioperative and postoperative functional outcome and safety of endoscopic treatment options for BPO in patients ≥ 75 years of age. Of particular importance is that all surgical techniques significantly improve the postoperative quality of life of patients in this age group compared to their preoperative quality of life.

A Peritoneal Purse-String Suture Prevents Symptomatic Lymphoceles in Retzius-Sparing Robot-Assisted Radical Prostatectomy.

BACKGROUND: The retzius-sparing approach for robotic-assisted radical prostatectomy (RARP) has been increasingly adopted. Symptomatic lymphoceles are a widespread complication of RARP with pelvic lymph node dissection. Here, we present a new technique, the peritoneal purse-string suture (PPSS), that seems to reduce the rate of symptomatic lymphoceles following retzius-sparing RARP with extended pelvic lymph node dissection (ePLND). METHODS: The radical prostatectomy and bilateral lymphadenectomy are performed through three separate peritoneal openings. The PPSS uses a single suture in a way similar to a purse-string suture; the openings of both lymphadenectomy fields are widened, and the rectovesical opening from the prostatectomy is simultaneously closed. This report retrospectively evaluates the perioperative and postoperative outcomes of two consecutive patient cohorts undergoing RARP with ePLND by a single surgeon between May 2015 and June 2019, one cohort prior to introducing PPSS as control (n = 145) and the other after introducing PPSS (n = 91). RESULTS: The two study groups were comparable on baseline characteristics, except ASA. There were no Clavien-Dindo grade IV-V complications, and comparable rates of grade I-III complications. The difference in postoperative lymphocele formation was 22% in PPSS versus 27% in the control group (p = 0.33). The rate of symptomatic lymphoceles was significantly lower in the PPSS group (3% vs. 10%, p = 0.047). CONCLUSION: The PPSS is a feasible procedure that reduces symptomatic lymphoceles in patients undergoing RARP with a retzius-sparing approach.

Membranous NECTIN-4 Expression Frequently Decreases during Metastatic Spread of Urothelial Carcinoma and Is Associated with Enfortumab Vedotin Resistance.

PURPOSE: The antibody-drug conjugate enfortumab vedotin (EV) releases a cytotoxic agent into tumor cells via binding to the membrane receptor NECTIN-4. EV was recently approved for patients with metastatic urothelial carcinoma (mUC) without prior assessment of the tumor receptor status as ubiquitous NECTIN-4 expression is assumed. Our objective was to determine the prevalence of membranous NECTIN-4 protein expression in primary tumors (PRIM) and patient-matched distant metastases (MET). EXPERIMENTAL DESIGN: Membranous NECTIN-4 protein expression was measured (H-score) by IHC in PRIM and corresponding MET (N = 137) and in a multicenter EV-treated cohort (N = 47). Progression-free survival (PFS) after initiation of EV treatment was assessed for the NECTIN-4-negative/weak (H-score 0-99) versus moderate/strong (H-score 100-300) subgroup. The specificity of the NECTIN-4 IHC staining protocol was validated by establishing CRISPR-Cas9-induced polyclonal NECTIN-4 knockouts. RESULTS: In our cohort, membranous NECTIN-4 expression significantly decreased during metastatic spread (Wilcoxon matched pairs P < 0.001; median H-score = 40; interquartile range, 0-140), with 39.4% of MET lacking membranous NECTIN-4 expression. In our multicenter EV cohort, absence or weak membranous NECTIN-4 expression (34.0% of the cohort) was associated with a significantly shortened PFS on EV (log-rank P < 0.001). CONCLUSIONS: Membranous NECTIN-4 expression is frequently decreased or absent in mUC tissue. Of note, the clinical benefit of EV strongly depends on membranous NECTIN-4 expression. Thus, our results are of highest clinical relevance and argue for a critical reconsideration of the current practice and suggest that the NECTIN-4 receptor status should be determined (ideally in a metastatic/progressive lesion) before initiation of EV. See related commentary by Aggen et al., p. 1377.

The Antimicrobial Resistance (AMR) Rates of Uropathogens in a Rural Western African Area-A Retrospective Single-Center Study from Kpando, Ghana.

Little is known about the antimicrobial resistance (AMR) status of uropathogens in Western Africa. We performed a retrospective evaluation of urine cultures collected from the rural Margret Marquart Catholic Hospital, Kpando, Ghana during the time period from October 2019−December 2021. Urine samples from 348 patients (median age 40 years, 52.6% male) were examined. Of these, 125 (35.9%) showed either fungal or bacterial growth, including Escherichia coli in 48 (38.4%), Candida species (spp.) in 29 (23.2%), Klebsiella spp. in 27 (21.6%), Proteus spp. in 12 (9.6%), Citrobacter spp. in 10 (8.0%), Salmonella spp. in 4 (3.2%), Staphylococcus spp. in 3 (2.4%), and Pseudomonas spp. in 2 (1.6%) cases. Two bacterial spp. were detected in 7 samples (5.6%). Antibiotic susceptibility testing showed resistance to a mean 8.6 out of 11 tested antibiotics per patient. Significant predictors (p < 0.05) of bacterial growth were age (OR 1.03), female sex (OR 3.84), and the number of pus cells (OR 1.05) and epithelial cells (OR 1.07) in urine microscopy. We observed an alarmingly high AMR rate among the uropathogens detected, even to reserve antibiotics. A similar resistance profile can be expected in West African patients living in high-income countries. These observations warrant the implementation of restrictive antibiotic protocols, together with the expansion of urine culture testing capacities, improvement of documentation and reporting of AMR rates, and continued research and development of new antibiotic therapies in order to stem the progression of AMR in this West African region.

[Patient-derived microtumors : Potential for therapeutic response prediction-a case study]. / Patientenabgeleitete Mikrotumoren : Eine Möglichkeit der Vorhersage des medikamentösen Therapieansprechens ­ ein Fallbericht.

BACKGROUND: In view of continued development of new oncological approaches, there is a high demand for personalized tumor therapy. However, fast and effective functional platforms for the prediction of individual patient response to drug therapy are largely unavailable. Various promising approaches have already been described for three-dimensional cell culture models, which represent cellular complexity and almost identical structures of the original tumor tissue. OBJECTIVES: Based on a case report, we show the capability and results of a novel test system using patient-derived microtumors (PDMs) and autologous tumor-infiltrating lymphocytes (TILs) for the prediction of response to cancer therapy. METHODS: We established PDMs and TILs from primary tumor tissue of a renal cell carcinoma metastasis. Using immunohistochemistry and multiplex florescence-activated cell sorting (FACS ) analyses, the PDMs and TILs were characterized regarding to histology and immunophenotype. Tumor-specific cytotoxicity of standard of care and investigational compounds were assessed. The results were compared to the patient's individual in vivo response to therapy. CONCLUSION: The cytotoxicity assay of PDMs and TILs showed a significant therapeutic response (p = 0.0004) to therapy with a programmed cell death protein 1 (PD-1) inhibitor and lenvatinib compared to the control. The in vitro results correlated positively with the in vivo data. In the future, patient-derived models could predict response to cancer therapy and may help to optimize treatment decision-making.

The Diagnostic Value of the Added MR Imaging of the Scrotum in the Preoperative Workup of Sonographically Indeterminate Testicular Lesions-A Retrospective Multicenter Analysis.

BACKGROUND: The purpose of this study was to retrospectively analyze the diagnostic accuracy of magnetic resonance imaging (MRI) examinations of the scrotum in comparison with standard ultrasound (US) and histopathology. METHODS: A retrospective multi-center analysis of MRI examinations of the scrotum performed between 06/2008 and 04/2021 was conducted. RESULTS: A total of n = 113 patients were included. A total of 53 histopathologies were available, with 52.8% malignant and 50.9% benign findings. Related to histopathology, imaging was true negative, false negative, false positive, and true positive in 4.1%, 2.1%, 25.0% and 37.5% for standard ultrasound (US) and 9.1%, 1.8%, 25.5% and 43.6% for MRI. Sensitivity, specificity, positive predictive value and negative predictive value were 94.7%, 20.0%, 36.0% and 88.9% for US and 85.7%, 72.8%, 52.1% and 93.7% for MRI, respectively. Benign lesions were significantly smaller than malignant ones in standard US (p = 0.001), histopathology (p = 0.001) and MRI (p = 0.004). The size of malignant tumors did not differ significantly between histopathology and standard US (0.72) and between histopathology and MRI (p = 0.88). CONCLUSIONS: MRI shows good sensitivity and specificity for the estimation of testicular tumors in this collective. Benign lesions are significantly smaller than malignant ones. Both MRI and US can estimate the size of malignant tumors adequately.

Versatility and clinical effectiveness of a synthetic sealing hemostatic patch as alternative to parenchyma suturing in laparoscopic partial nephrectomy.

BACKGROUND: Improvements in laparoscopic partial nephrectomy (LPN) in order to minimize perioperative warm ischemia time (WIT), complications, and consequently patient outcome are desirable. Veriset™ is a ready-to-use hemostatic patch of absorbable oxidized cellulose and hydrogel components that has earlier been implemented in vascular and hepatic surgery. We report our experience using this device in LPN. METHODS: Patients with a solitary malignant renal mass suspicious for renal cancer underwent LPN with either the use of Veriset™ hemostatic patch (n = 40) or conventional suture technique (n = 40). Patient characteristics, operation time and WIT, postoperative course and complications were recorded retrospectively. Tumor complexity was calculated according to the R.E.N.A.L. score. Outcome was determined according to the "trifecta" criteria (negative surgical margin, WIT < 25 min, no complications within 30 days). RESULTS: No significant differences with regard to clinical parameters and median R.E.N.A.L. score (6) were observed between both groups. Operation time (mean 127.1 min vs. 162. 8 min; p = 0.001) and WIT were both lower in the Veriset™ group (14.6 min vs. 20.6 min; p = 0.01). No differences in surgical margins (p = 0.602) and overall complication rates at 30 (p = 0.599) and 90 days (p = 0.611) postoperatively were noticed. The surgical outcome according to "trifecta" was achieved in 65% of patients using Veriset™ and in 57.5% of patients by suture closure, respectively. CONCLUSION: The hemostatic Veriset™ patch can successfully be implemented in LPN. Handling and application appear favorable, thereby reducing operation time and WIT. The present results suggest that the device may represent an alternative to parenchyma suturing in LPN.

Robotic Transrectal Computed Tomographic Ultrasound with Artificial Neural Network Analysis: First Validation and Comparison with MRI-Guided Biopsies and Radical Prostatectomy.

INTRODUCTION: There is still a lack of availability of high-quality multiparametric magnetic resonance imaging (mpMRI) interpreted by experienced uro-radiologists to rule out clinically significant PC (csPC). Consequently, we developed a new imaging method based on computed tomographic ultrasound (US) supported by artificial neural network analysis (ANNA). METHODS: Two hundred and two consecutive patients with visible mpMRI lesions were scanned and recorded by robotic CT-US during mpMRI-TRUS biopsy. Only significant index lesions (ISUP ≥2) verified by whole-mount pathology were retrospectively analyzed. Their visibility was reevaluated by 2 blinded investigators by grayscale US and ANNA. RESULTS: In the cohort, csPC was detected in 105 cases (52%) by mpMRI-TRUS biopsy. Whole-mount histology was available in 44 cases (36%). In this subgroup, mean PSA level was 8.6 ng/mL, mean prostate volume was 33 cm3, and mean tumor volume was 0.5 cm3. Median PI-RADS and ISUP of index lesions were 4 and 3, respectively. Index lesions were visible in grayscale US and ANNA in 25 cases (57%) and 30 cases (68%), respectively. Combining CT-US-ANNA, we detected index lesions in 35 patients (80%). CONCLUSIONS: The first results of multiparametric CT-US-ANNA imaging showed promising detection rates in patients with csPC. US imaging with ANNA has the potential to complement PC diagnosis.

Oncological validation of bone turnover markers c-terminal telopeptide of type I collagen (1CTP) and peptides n-terminal propeptide of type I procollagen (P1NP) in patients with prostate cancer and bone metastases.

BACKGROUND: Bone formation markers c-terminal telopeptide of type I collagen (1CTP) and peptides n-terminal propeptide of type I procollagen (P1NP) were reported to be increased in patients with prostate cancer (PC) and bone metastases. The objective of the presented study was to investigate the utility of serum 1CTP and P1NP values in the diagnosis of bone metastases and in predicting oncological outcome in patients with PC. METHODS: In total, serum samples of 186 patients were included retrospectively including 53 (28.50%) benign prostatic hyperplasia (BPH) patients and 133 (71.50%) PC-patients. The group of patients with PC consisted of 58 patients with non-metastatic PC (cM0) (43.61%) and 70 (52.63%) patients with bone metastases (cM1b). Serum 1CTP and P1NP were measured by radioimmunoassay (RIA). Results were compared to clinical variables including oncologic follow-up data by univariate and multivariate analyses. RESULTS: Median 1CTP concentrations were significantly higher in patients with PC compared to the BPH group [5.08 (range, 1.73-158.00) vs. 4.00 (range, 2.18-34.19) µg/L, P=0.019]. However, no significant difference of P1NP levels could be shown for these groups. With median values of 6.04 (1.73-158.00) and 3.91 µg/L (2.04-34.51) for 1CTP and 48.60 (9.12-1,074.37) and 33.90 (8.72-149.30) for P1NP both markers were altered in cM1b patients compared to cM0 patients (P=0.001 each). Furthermore, cancer-specific survival (CSS) and overall survival (OS) were significantly shorter in cM1b patients with higher 1CTP concentrations (P=0.037 and P=0.019, respectively), whereas no associations of P1NP and outcomes were observed. CONCLUSIONS: The present study confirms that increased levels of 1CTP and P1NP concentrations are associated with presence of metastatic disease in the bone. Moreover, these markers are able to predict clinical course in PC patients with bone metastases. The potential use of these markers for treatment selection in advanced PC remains to be determined.

Preexisting and Post-COVID-19 Immune Responses to SARS-CoV-2 in Patients with Cancer.

Patients with cancer, in particular patients with hematologic malignancies, are at increased risk for critical illness upon COVID-19. We here assessed antibody as well as CD4+ and CD8+ T-cell responses in unexposed and SARS-CoV-2-infected patients with cancer to characterize SARS-CoV-2 immunity and to identify immunologic parameters contributing to COVID-19 outcome. Unexposed patients with hematologic malignancies presented with reduced prevalence of preexisting SARS-CoV-2 cross-reactive CD4+ T-cell responses and signs of T-cell exhaustion compared with patients with solid tumors and healthy volunteers. Whereas SARS-CoV-2 antibody responses did not differ between patients with COVID-19 and cancer and healthy volunteers, intensity, expandability, and diversity of SARS-CoV-2 T-cell responses were profoundly reduced in patients with cancer, and the latter associated with a severe course of COVID-19. This identifies impaired SARS-CoV-2 T-cell immunity as a potential determinant for dismal outcome of COVID-19 in patients with cancer. SIGNIFICANCE: This first comprehensive analysis of SARS-CoV-2 immune responses in patients with cancer reports on the potential implications of impaired SARS-CoV-2 T-cell responses for understanding pathophysiology and predicting severity of COVID-19, which in turn might allow for the development of therapeutic measures and vaccines for this vulnerable patient population.See related commentary by Salomé and Horowitz, p. 1877.This article is highlighted in the In This Issue feature, p. 1861.