Natalia Leva

Higher rates of upgrading and upstaging in older patients undergoing radical prostatectomy and qualifying for active surveillance

To determine pathological and oncological outcomes of patients diagnosed with low‐risk prostate cancer in two age cohorts who underwent radical prostatectomy (RP) and qualified for active surveillance (AS) according to Prostate Cancer Research International: Active Surveillance (PRIAS) criteria, as AS for low‐risk prostate cancer represents an acceptable management strategy especially for older patients.

Group B Streptococcus colonization by HIV status in pregnant women: prevalence and risk factors.

OBJECTIVES To examine the prevalence of and risk factors for group B Streptococcus (GBS) colonization in an HIV-infected and uninfected pregnant population. METHODS We conducted a retrospective double cohort study comparing the prevalence of GBS colonization between 90 HIV-infected and 1947 uninfected women attending prenatal care at San Francisco General Hospital, an urban public hospital affiliated with the University of California, San Francisco. We investigated risk factors for GBS colonization, including age, ethnicity, obesity, diabetes, alcohol or illicit drug use, tobacco use, degree of immunosuppression, and infectious comorbidities. RESULTS In the multivariable analysis, HIV serostatus was not independently associated with GBS colonization (odds ratio [OR] 1.00, 95% confidence interval [CI] 0.62-1.62). Obesity (OR 1.53, 95% CI 1.13-2.07), white race (OR 1.89, 95% CI 1.30-2.75), and black race (OR 1.78, 95% CI 1.32-2.41) were independently associated with increased maternal GBS colonization. Among HIV-infected women, univariate analysis showed an association between GBS colonization and detectable HIV-1 plasma viral load at the time of rectovaginal culture (p<0.05). Mean CD4 lymphocyte count, infectious comorbidities, and HIV-1 plasma viral load at delivery were not associated with GBS colonization in HIV-infected pregnant women. CONCLUSIONS HIV-1 infection is not a risk factor for GBS colonization among an ethnically diverse pregnant population at San Francisco General Hospital, although our data suggest that among HIV-infected women, plasma HIV-1 viremia may be associated with GBS colonization. Interventions that diminish HIV-1 plasma viral load and, perhaps, genital tract shedding of HIV may be associated with a reduced risk of GBS colonization in future studies.

Comparison of surgical technique (Open vs. Laparoscopic) on pathological and long term functional outcomes following radical prostatectomy

BackgroundFew studies to date have directly compared outcomes of retropubic (RRP) and laparoscopic (LRP) radical prostatectomy. We investigated a single institution experience with RRP and LRP with respect to functional and pathological outcomes.Methods168 patients who underwent RRP were compared to 171 patients who underwent LRP at our institution. Pathological and functional outcomes including postoperative urinary incontinence and erectile dysfunction (ED) of the two cohorts were examined.ResultsPatients had bilateral, unilateral and no nerve sparing technique performed in 83.3%, 1.8% and 14.9% of cases for RRP and 23.4%, 22.8% and 53.8% of cases for LRP, respectively (p < 0.001). Overall positive surgical margin rates were 22.2% among patients who underwent RRP compared to 26.5% of patients who underwent LRP (p = 0.435). Based upon pads/day, urinary continence postoperatively was achieved in 83.2% and 82.8% for RRP and LRP, respectively (p = 0.872). Analysis on postoperative ED was limited due to lack of information on the preoperative erectile status. However, postoperatively there were no differences with respect to ED between the two cohorts (p = 0.151). Based on ICIQ-scores, surgeons with more experience had lower rates of postoperative incontinence irrespective of surgical technique (p = 0.001 and p < 0.001 for continuous and stratified data, respectively).ConclusionsRRP and LRP represent effective surgical approaches for the treatment of clinically localized prostate cancer. Pathological outcomes are excellent for both surgical techniques. Functional outcomes including postoperative urinary incontinence and ED are comparable between the cohorts. Surgeon experience is more relevant than surgical technique applied.

Time to viral load suppression in antiretroviral‐naive and ‐experienced HIV‐infected pregnant women on highly active antiretroviral therapy: implications for pregnant women presenting late in gestation

To compare time to achieve viral load <400 copies/ml and <1000 copies/ml in HIV‐infected antiretroviral (ARV) ‐naive versus ARV‐experienced pregnant women on highly active antiretroviral therapy (HAART).

Missed Opportunities to Decrease Radiation Exposure in Children with Renal Trauma

Purpose: Efforts have been made to reduce use of computerized tomography in children with blunt abdominal injury. Computerized tomography may be overused in pediatric patients with renal trauma. Materials and Methods: We performed a retrospective chart review of all renal trauma patients younger than 18 years old treated at 2 urban trauma centers from 2002 to 2016. We collected demographic and clinical characteristics, renal trauma grades, urological interventions, and timing and use of computerized tomography and renal ultrasound. Results: During the study period 145 patients presented with blunt renal trauma. During hospitalization 46 patients (32%) underwent repeat computerized tomography. About 20% of repeat computerized tomograms were performed less than 48 hours after the first scan. After controlling for center, isolated injury (yes/no), stent placement, age and surgical interventions (yes/no) patients who underwent delayed imaging on their first scan had decreased odds of undergoing a second computerized tomogram (adjusted OR 0.2, 95% CI 0.05–0.9, p = 0.04). Number needed to treat to prevent 1 repeat scan in high grade renal trauma patients was 3 (95% CI 2–4). Estimated sensitivity and specificity for ultrasound monitoring to detect an abnormality requiring urological intervention are 50% and 94%, respectively. Conclusions: Repeat computerized tomography in pediatric patients with renal trauma is common. Obtaining delayed imaging on the initial scan in patients with high grade renal trauma may prevent repeat scans. Renal ultrasound provides diagnostic usefulness in monitoring kidney injuries and should be considered before repeating computerized tomography.

Risk prediction models for biochemical recurrence after radical prostatectomy using prostate-specific antigen and Gleason score

Many computer models for predicting the risk of prostate cancer have been developed including for prediction of biochemical recurrence (BCR). However, models for individual BCR free probability at individual time-points after a BCR free period are rare. Follow-up data from 1656 patients who underwent laparoscopic radical prostatectomy (LRP) were used to develop an artificial neural network (ANN) to predict BCR and to compare it with a logistic regression (LR) model using clinical and pathologic parameters, prostate-specific antigen (PSA), margin status (R0/1), pathological stage (pT), and Gleason Score (GS). For individual BCR prediction at any given time after operation, additional ANN, and LR models were calculated every 6 months for up to 7.5 years of follow-up. The areas under the receiver operating characteristic (ROC) curve (AUC) for the ANN (0.754) and LR models (0.755) calculated immediately following LRP, were larger than that for GS (AUC: 0.715; P = 0.0015 and 0.001), pT or PSA (AUC: 0.619; P always <0.0001) alone. The GS predicted the BCR better than PSA (P = 0.0001), but there was no difference between the ANN and LR models (P = 0.39). Our ANN and LR models predicted individual BCR risk from radical prostatectomy for up to 10 years postoperative. ANN and LR models equally and significantly improved the prediction of BCR compared with PSA and GS alone. When the GS and ANN output values are combined, a more accurate BCR prediction is possible, especially in high-risk patients with GS ≥7.

MP48-10 VALIDATION OF NRF2 PATHWAY DYSREGULATION IN UROTHELIAL CARCINOMA

INTRODUCTION AND OBJECTIVES: Integrin signaling plays an important role in cellular proliferation and migration via interactions with extracellular matrix proteins. Prior studies indicate that integrin signaling facilitates tumor invasion and metastasis, and there are several ongoing clinical trials using agents that modulate this pathway. We recently identified clonal enrichment in mutations in the integrin cell surface interactions pathways in advanced urothelial carcinoma. An ideal strategy for investigating integrin signaling is via 3D organoid culture, maintaining intercellular interactions that replicate the epithelial microenvironment. We hypothesize that pharmacologic integrin signaling modulation will impair organoid growth in bladder cancer cells and demonstrate a therapeutic utility for this approach. METHODS: RT4 human bladder cancer cell line was used as well as a second cell line established from a patient-derived bladder cancer sample (PM748). Cells were grown in 3D organoid culture as previously described. For in vitro integrin modulation, defactinib, an orally-bioavailable selective inhibitor of focal adhesion kinase (FAK, a convergent and conserved enzyme activated by integrin ligand binding), was used. SDS-PAGE and immunoblotting were performed to show in vitro FAK inhibition. Single cell suspensions and organoids were plated in the presence of various concentrations of defactinib to determine the impact on organoid formation and regression. RESULTS: Defactinib caused a dose-dependent decrease in autophosphorylation of FAK for both cell lines, demonstrating effective FAK inhibition. 3D culture of single cells with defactinib produced a dose-dependent decrease in organoid size after 96 hours (mean size for DMSO only, 100nM, 1uM, and 10uM were 128um, 75um, 48um, and 26um, respectively; p<0.0001 versus DMSO for all dilutions). Established organoids showed a dose-dependent regression in size after 72 hours of defactinib exposure (mean size for DMSO, 100nM, 1uM, and 10uM were 225um, 96um, 70um, and 34um, respectively; p<0.0001 versus DMSO). Experiments utilizing Crispr-Cas9-mediated FAK knock-out as well as in vivo studies with FAK inhibitors in xenograft models are currently underway. CONCLUSIONS: Integrin modulation via FAK inhibition with defactinib causes both inhibition of organoid formation as well as regression of formed organoids, and the effects are seen at concentrations well below the cytotoxic range for the drug. This study suggests a utility for these agents in bladder cancer treatment.

Propensity Score Vergleich der verschiedenen radikalen Operationstechniken beim high risk Prostatakarzinom

INTRODUCTION The optimal surgical treatment of patients with a high risk prostate cancer (PCa) in terms of radical prostatectomy (RP) is still controversial: open retropubic RP (RRP), laparoscopic RP (LRP), or robot-assisted (RARP). We aimed to investigate the influence of the different surgical techniques on pathologic outcome and biochemical recurrence. PATIENTS AND METHODS A total of 805 patients with a high risk PCa (PSA >20 ng/mL, Gleason Score ≥8, or clinical stage ≥cT2c) were included. A comparison of 407 RRP patients with 398 minimally invasive cases (LRP+RARP) revealed significant confounders. Therefore all 110 RARP cases were propensity score (PS) matched 1:1 with LRP and RRP patients. PS included age, clinical stage, preoperative PSA, biopsy Gleason score, surgeons experience and application of a nerve sparing technique. Comparison of overall survival (OS) and recurrence-free survival (RFS) was done with the log rank test. Predictors of RFS were analyzed by means of Cox regression models. RESULTS Within the post-matching cohort of 330 patients a pathologic Gleason score < 7, = 7 and > 7 was found in 1.8, 55.5 and 42.7% for RARP, in 8.2, 36.4, 55.5% for LRP and in 0, 60.9 and 39.1% for RRP (p=0.004 for RARP vs. LRP and p=0.398 for RARP vs. RRP). Differences in histopathologic stages were not statistically significant. The overall positive surgical margin rate (PSM) as well as PSM for ≥ pT3 were not different. PSM among patients with pT2 was found in 15.7, 14.0 and 20.0% for RARP, LRP and RRP (statistically not significant). The respective mean 3-year RFS rates were 41.4, 77.9, 54.1% (p<0.0001 for RARP vs. LRP and p=0.686 for RARP vs. RRP). The mean 3-year OS was calculated as 95.4, 98.1 and 100% respectively (statistically not significant). CONCLUSION RARP for patients with a high risk PCa reveals similar pathologic and oncologic outcomes compared with LRP and RRP.