A Novel PD-L1 Antibody Promotes Antitumor Function of Peripheral Cytotoxic Lymphocytes after Radical Nephrectomy in Patients with Renal Cell Carcinoma.

The intrinsic and acquired resistance to PD-1/PD-L1 immune checkpoint blockade is an important challenge for patients and clinicians because no reliable tool has been developed to predict individualized response to immunotherapy. In this study, we demonstrate the translational relevance of an ex vivo functional assay that measures the tumor cell killing ability of patient-derived CD8 T and NK cells (referred to as "cytotoxic lymphocytes," or CLs) isolated from the peripheral blood of patients with renal cell carcinoma. Patient-derived PBMCs were isolated before and after nephrectomy from patients with renal cell carcinoma. We compared the efficacy of U.S. Food and Drug Administration (FDA)-approved PD-1/PD-L1 inhibitors (pembrolizumab, nivolumab, atezolizumab) and a newly developed PD-L1 inhibitor (H1A Ab) in eliciting cytotoxic function. CL activity was improved at 3 mo after radical nephrectomy compared with baseline, and it was associated with higher circulating levels of tumor-reactive effector CD8 T cells (CD11ahighCX3CR1+GZMB+). Treatment of PBMCs with FDA-approved PD-1/PD-L1 inhibitors enhanced tumor cell killing activity of CLs, but a differential response was observed at the individual-patient level. H1A demonstrated superior efficacy in promoting CL activity compared with FDA-approved PD-1/PD-L1 inhibitors. PBMC immunophenotyping by mass cytometry revealed enrichment of effector CD8 T and NK cells in H1A-treated PBMCs and immunosuppressive regulatory T cells in atezolizumab-treated samples. Our study lays the ground for future investigation of the therapeutic value of H1A as a next-generation immune checkpoint inhibitor and the potential of measuring CTL activity in PBMCs as a tool to predict individual response to immune checkpoint inhibitors in patients with advanced renal cell carcinoma.

Value of 3-Tesla multiparametric magnetic resonance imaging and targeted biopsy for improved risk stratification in patients considered for active surveillance.

OBJECTIVE: To evaluate the role of multiparametric magnetic resonance imaging (mpMRI) of the prostate and transrectal ultrasonography guided biopsy (TRUS-Bx) with visual estimation in early risk stratification of patients with prostate cancer on active surveillance (AS). PATIENTS AND METHODS: Patients with low-risk, low-grade, localised prostate cancer were prospectively enrolled and submitted to a 3-T 16-channel cardiac surface coil mpMRI of the prostate and confirmatory biopsy (CBx), which included a standard biopsy (SBx) and visual estimation-guided TRUS-Bx. Cancer-suspicious regions were defined using Prostate Imaging Reporting and Data System (PI-RADS) scores. Reclassification occurred if CBx confirmed the presence of a Gleason score ≥7, greater than three positive fragments, or ≥50% involvement of any core. The performance of mpMRI for the prediction of CBx results was assessed. Univariate and multivariate logistic regressions were performed to study relationships between age, prostate-specific antigen (PSA) level, PSA density (PSAD), number of positive cores in the initial biopsy, and mpMRI grade on CBx reclassification. Our report is consistent with the Standards of Reporting for MRI-targeted Biopsy Studies (START) guidelines. RESULTS: In all, 105 patients were available for analysis in the study. From this cohort, 42 (40%) had PI-RADS 1, 2, or 3 lesions and 63 (60%) had only grade 4 or 5 lesions. Overall, 87 patients underwent visual estimation TRUS-Bx. Reclassification among patients with PI-RADS 1, 2, 3, 4, and 5 was 0%, 23.1%, 9.1%, 74.5%, and 100%, respectively. Overall, mpMRI sensitivity, specificity, positive predictive value, and negative predictive value for disease reclassification were 92.5%, 76%, 81%, and 90.5%, respectively. In the multivariate analysis, only PSAD and mpMRI remained significant for reclassification (P < 0.05). In the cross-tabulation, SBx would have missed 15 significant cases detected by targeted biopsy, but SBx did detect five cases of significant cancer not detected by targeted biopsy alone. CONCLUSION: Multiparametric magnetic resonance imaging is a significant tool for predicting cancer severity reclassification on CBx among AS candidates. The reclassification rate on CBx is particularly high in the group of patients who have PI-RADS grades 4 or 5 lesions. Despite the usefulness of visual-guided biopsy, it still remains highly recommended to retrieve standard fragments during CBx in order to avoid missing significant tumours.

A prognostic model for survival after palliative urinary diversion for malignant ureteric obstruction: a prospective study of 208 patients.

OBJECTIVE: To identify factors associated with survival after palliative urinary diversion (UD) for patients with malignant ureteric obstruction (MUO) and create a risk-stratification model for treatment decisions. PATIENTS AND METHODS: We prospectively collected clinical and laboratory data for patients who underwent palliative UD by ureteric stenting or percutaneous nephrostomy (PCN) between 1 January 2009 and 1 November 2011 in two tertiary care university hospitals, with a minimum 6-month follow-up. Inclusion criteria were age >18 years and MUO confirmed by computed tomography, ultrasonography or magnetic resonance imaging. Factors related to poor prognosis were identified by Cox univariable and multivariable regression analyses, and a risk stratification model was created by Kaplan-Meier survival estimates at 1, 6 and 12 months, and log-rank tests. RESULTS: The median (range) survival was 144 (0-1084) days for the 208 patients included after UD (58 ureteric stenting, 150 PCN); 164 patients died, 44 (21.2%) during hospitalisation. Overall survival did not differ by UD type (P = 0.216). The number of events related to malignancy (≥4) and Eastern Cooperative Oncology Group (ECOG) index (≥2) were associated with short survival on multivariable analysis. These two risk factors were used to divide patients into three groups by survival type: favourable (no factors), intermediate (one factor) and unfavourable (two factors). The median survival at 1, 6, and 12 months was 94.4%, 57.3% and 44.9% in the favourable group; 78.0%, 36.3%, and 15.5% in the intermediate group; and 46.4%, 14.3%, and 7.1% in the unfavourable group (P < 0.001). CONCLUSIONS: Our stratification model may be useful to determine whether UD is indicated for patients with MUO.

Optimal Approach to Small Unilateral Testicular Nodules-Can We Reliably Predict Tumor Histology Based on Size?

INTRODUCTION: We evaluated primary testicular tumor characteristics associated with nongerm cell tumor histology and potential appropriateness for testis sparing surgery in selected patients from our institution. METHODS: We retrospectively reviewed medical records of patients undergoing surgery for testicular masses between 2003 and 2015. We included patients with unilateral testicular tumors, normal preoperative serum tumor markers and no preoperative evidence of metastatic spread. Demographic and clinical information were extracted. The primary outcome studied was tumor pathology, germ cell tumor histology vs nongerm cell histology. We compared patients in these cohorts based on the testicular tumor size. RESULTS: A total of 48 patients met study criteria, 18 (37.5%) of whom had a final pathology consistent with nongerm cell histology. In general, the median tumor size was less in the nongerm cell group (11 mm vs 27 mm, p=0.001). Tumor size less than 2 cm was associated with increased likelihood of nongerm cell histology (p=0.003) with 61.9% of those with tumors less than 2 cm harboring nongerm cell tumors and therefore likely appropriate for organ-sparing surgery. A receiver operating characteristic analysis demonstrated a maximum sensitivity and specificity for selecting masses with normal tumor markers as having nongerm cell histology at a size cutoff of 18 mm. CONCLUSIONS: It appears that a majority of patients with localized small testicular masses and nonelevated tumor markers will have nongerm cell histology, which makes them potentially eligible for testicular sparing surgery at centers with expertise in intraoperative frozen section analysis.

Is a safety guidewire needed for retrograde ureteroscopy?

INTRODUCTION: It is generally advised to have a safety guidewire (SGW) present during ureteroscopy (URS) to manage possible complications. However, it increases the strenght needed to insert and retract the endoscope during the procedure, and, currently, there is a lack of solid data supporting the need for SGW in all procedures. We reviewed the literature about SGW utilization during URS. METHOD: A review of the literature was conducted through April 2017 using PubMed, Ovid, and The Cochrane Library databases to identify relevant studies. The primary outcome was to report stone-free rates, feasibility, contraindications to and complications of performing intrarenal retrograde flexible and semi-rigid URS without the use of a SGW. RESULTS: Six studies were identified and selected for this review, and overall they included 1,886 patients where either semi-rigid or flexible URS was performed without the use of a SGW for the treatment of urinary calculi disease. Only one study reported stone-free rates with or without SGW at 77.1 and 85.9%, respectively (p=0.001). None of the studies showed increased rates of complications in the absence of SGW and one of them showed more post-endoscopic ureteral stenosis whenever SGW was routinely used. All studies recommended utilization of SGW in complicated cases, such as ureteral stones associated with significant edema, ureteral stricture, abnormal anatomy or difficult visualization. CONCLUSION: Our review showed a lack of relevant data supporting the use of SGW during retrograde URS. A well-designed prospective randomized trial is in order.

Laparoscopic Versus Percutaneous Cryoablation of Small Renal Mass: Systematic Review and Cumulative Analysis of Comparative Studies.

The objective of this study was to compare the surgical, oncological, and functional outcomes of laparoscopic and percutaneous cryoablation for the treatment of small renal masses. A systematic review of the literature was performed through March 2016 using PubMed, Scopus, and Ovid databases. Article selection proceeded according to the search strategy on the basis of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. Only studies that compared laparoscopic and percutaneous kidney cryoablation were included in the meta-analysis. Eleven retrospective comparative studies were identified and selected for the analysis, including 1725 cases: 804 (46.6%) percutaneous and 921 (53.4%) laparoscopic cryoablations. Percutaneous cryoablation was performed more frequently for posterior tumors (P < .001), whereas laparoscopy was more common for endophytic lesions (P = .01). The length of follow-up was longer for laparoscopy (P < .001). Percutaneous cryoablation was associated with a significantly shorter hospital stay (P < .001). A lower likelihood of residual disease was recorded for laparoscopic (P = .003), whereas tumor recurrence rate favored percutaneous cryoablation (P = .02). The 2 procedures were similar for recurrence-free survival (P = .08), and overall survival (P = .51). No significant difference was found in postoperative estimated glomerular filtration rate (P = .78). Laparoscopic and percutaneous kidney cryoablation offer similar favorable oncological outcomes with minimal effect on renal function. The percutaneous access can offer shorter hospital stay and faster recovery, which can be appealing in an era of cost restraint.

Is a safety guidewire needed for retrograde ureteroscopy? / Fio guia de segurança é necessário na ureteroscopia?

Summary Introduction: It is generally advised to have a safety guidewire (SGW) present during ureteroscopy (URS) to manage possible complications. However, it increases the strenght needed to insert and retract the endoscope during the procedure, and, currently, there is a lack of solid data supporting the need for SGW in all procedures. We reviewed the literature about SGW utilization during URS. Method: A review of the literature was conducted through April 2017 using PubMed, Ovid, and The Cochrane Library databases to identify relevant studies. The primary outcome was to report stone-free rates, feasibility, contraindications to and complications of performing intrarenal retrograde flexible and semi-rigid URS without the use of a SGW. Results: Six studies were identified and selected for this review, and overall they included 1,886 patients where either semi-rigid or flexible URS was performed without the use of a SGW for the treatment of urinary calculi disease. Only one study reported stone-free rates with or without SGW at 77.1 and 85.9%, respectively (p=0.001). None of the studies showed increased rates of complications in the absence of SGW and one of them showed more post-endoscopic ureteral stenosis whenever SGW was routinely used. All studies recommended utilization of SGW in complicated cases, such as ureteral stones associated with significant edema, ureteral stricture, abnormal anatomy or difficult visualization. Conclusion: Our review showed a lack of relevant data supporting the use of SGW during retrograde URS. A well-designed prospective randomized trial is in order.

Resumo Introdução: O uso de fio guia de segurança (FGS) costuma ser recomendado para a realização de ureteroscopia para prevenir e solucionar complicações durante o procedimento. Seu uso, porém, aumenta a força necessária para manipular o aparelho endoscópico dentro da luz ureteral e, atualmente, existe uma carência de dados consistentes que indiquem o uso do FGS em todos os procedimentos. Método: Uma revisão da literatura foi realizada em abril de 2017 utilizando as ferramentas PubMed, Ovid e The Cochrane Library para identificar estudos relevantes. O desfecho primário da análise foi reportar taxas de resolução dos cálculos, viabilidade, contraindicações e complicações relacionadas ao não uso do FGS. Resultados: Seis estudos foram incluídos na análise, totalizando 1.886 pacientes, nos quais foi realizada ureteroscopia semirrígida ou flexível sem o uso do FGS no tratamento de cálculos renais ou ureterais. Somente um estudo relatou taxa livre de cálculos com ou sem FGS, sendo 77,1 e 85,9%, respectivamente (p=0.001). Todos os estudos mostraram não haver aumento da taxa de complicação na ausência do FGS e um deles relatou aumento de estenose ureteral pós-endoscopia no grupo que utilizou o FGS. Todos os estudos recomendam o uso do FGS em casos complicados, como cálculos ureterais associados a edema de mucosa, estenose ureteral, anomalias anatômicas ou dificuldade de visualização do cálculo. Conclusão: Nossa revisão mostrou que faltam dados relevantes para justificar o uso do FGS durante a ureteroscopia.