Safety and immunogenicity of novel 5T4 viral vectored vaccination regimens in early stage prostate cancer: a phase I clinical trial.

BACKGROUND: Prostate cancer (PCa) has been under investigation as a target for antigen-specific immunotherapies in metastatic disease settings for the last two decades leading to a licensure of the first therapeutic cancer vaccine, Sipuleucel-T, in 2010. However, neither Sipuleucel-T nor other experimental PCa vaccines that emerged later induce strong T-cell immunity. METHODS: In this first-in-man study, VANCE, we evaluated a novel vaccination platform based on two replication-deficient viruses, chimpanzee adenovirus (ChAd) and MVA (Modified Vaccinia Ankara), targeting the oncofetal self-antigen 5T4 in early stage PCa. Forty patients, either newly diagnosed with early-stage PCa and scheduled for radical prostatectomy or patients with stable disease on an active surveillance protocol, were recruited to the study to assess the vaccine safety and T-cell immunogenicity. Secondary and exploratory endpoints included immune infiltration into the prostate, prostate-specific antigen (PSA) change, and assessment of phenotype and functionality of antigen-specific T cells. RESULTS: The vaccine had an excellent safety profile. Vaccination-induced 5T4-specific T-cell responses were measured in blood by ex vivo IFN-γ ELISpot and were detected in the majority of patients with a mean level in responders of 198 spot-forming cells per million peripheral blood mononuclear cells. Flow cytometry analysis demonstrated the presence of both CD8+ and CD4+ polyfunctional 5T4-specific T cells in the circulation. 5T4-reactive tumor-infiltrating lymphocytes were isolated from post-treatment prostate tissue. Some of the patients had a transient PSA rise 2-8 weeks following vaccination, possibly indicating an inflammatory response in the target organ. CONCLUSIONS: An excellent safety profile and T-cell responses elicited in the circulation and also detected in the prostate gland support the evaluation of the ChAdOx1-MVA 5T4 vaccine in efficacy trials. It remains to be seen if this vaccination strategy generates immune responses of sufficient magnitude to mediate clinical efficacy and whether it can be effective in late-stage PCa settings, as a monotherapy in advanced disease or as part of multi-modality PCa therapy. To address these questions, the phase I/II trial, ADVANCE, is currently recruiting patients with intermediate-risk PCa, and patients with advanced metastatic castration-resistant PCa, to receive this vaccine in combination with nivolumab. TRIAL REGISTRATION: The trial was registered with the U.S. National Institutes of Health (NIH) Clinical Trials Registry (ClinicalTrials.gov identifier NCT02390063).

Improving Staging in Bladder Cancer: The Increasing Role of Multiparametric Magnetic Resonance Imaging.

CONTEXT: In bladder cancer (BCa) patients, accurate local and regional tumor staging is required when planning treatment. Clinical understaging frequently occurs and leads to undertreatment of the disease, with a negative impact on survival. An improvement in staging accuracy could be attained by advances in imaging. Magnetic resonance imaging (MRI) is currently the best imaging technique for locoregional staging for several malignancies because of its superior soft tissue contrast resolution with the advantage of avoiding exposure to ionizing radiation. Important improvements in MRI technology have led to the introduction of multiparametric MRI (mpMRI), which combines anatomic and functional evaluation. OBJECTIVE: To review the fundamentals of mpMRI in BCa and to provide a contemporary overview of the available data on the role of this emerging imaging technology. EVIDENCE ACQUISITION: A nonsystematic literature search using the Medline and Cochrane Library databases was performed up to March 2016. Additional articles were retrieved by cross-matching references of selected articles. Only articles reporting complete data with regard to image acquisition protocols, locoregional staging, monitoring response to therapy, and detection of locoregional recurrence after primary treatment in BCa patients were selected. EVIDENCE SYNTHESIS: Standardization of acquisition and reporting protocols for bladder mpMRI is paramount. Combining anatomic and functional sequences improves the accuracy of local tumor staging compared with conventional imaging alone. Diffusion-weighted imaging may distinguish BCa type and grade. Functional sequences are capable of monitoring response to chemotherapy and radiation therapy. Diffusion-weighted imaging enhanced by lymphotropic nanoparticles showed high accuracy in pelvic lymph node staging compared with conventional cross-sectional imaging. CONCLUSIONS: In BCa patients, mpMRI appears a promising tool for accurate locoregional staging, predicting tumor aggressiveness and monitoring response to therapy. Further large-scale studies are needed to confirm these findings. PATIENT SUMMARY: Better imaging through improved technology will improve outcomes in bladder cancer patients. We reviewed the emerging use of multiparametric magnetic resonance imaging for staging and monitoring bladder cancer. Multiparametric magnetic resonance imaging appears more accurate than current methods for local and nodal staging and monitoring tumor response to treatment, but requires further investigation.

MINI PCNL in a pediatric population.

PURPOSE: We report our initial experience of MINI percutaneous nephrolithotomy (PCNL) in a pediatric population using a miniature nephroscope through a 16F metal access sheath. METHODS: All pediatric patients who underwent PCNL from August 2007 to September 2010 using a 14F miniature nephroscope through a 16F metal access sheath for renal stone extraction were evaluated. Patients' demographic details, procedural information, and posttreatment outcomes were prospectively documented. RESULTS: A total of 23 MINI PCNLs were performed on 23 kidneys of 12 patients whose ages ranged from 1.6 to 14.6 years. The median stone burden was 3.44 cm(2), and there were 11 "Staghorn" stones. The procedure was primary via a single puncture in 19 kidneys and secondary using a preexisting nephrostomy tract in 4 kidneys. Access was successful in all primary and two secondary cases, for a total of success rate of 91.3 %. Stones were fragmented using a Holmium laser and/or lithoclast, and fragments were irrigated or sequentially removed by various stone grasping devices. The mean procedural X-ray screening time and total stone extraction period were 4.5 and 109.4 min, respectively. The primary stone free rate was 83.6 %, which increased to 90.5 % after treating the residual fragments. Postoperative hydrothorax developed in one patient, which required a chest drain. Symptoms of chest infection and positive urine culture were detected in one and two patients, respectively. CONCLUSIONS: Our initial experience supports previous reports that MINI PCNL is safe and effective for the management of renal stones in children.

Unenhanced CT for the evaluation of acute ureteric colic: the essential pictorial guide.

Acute ureteric colic is a common emergency, often dealt with by the emergency physician or general practitioner and referred on to the urologist. Unenhanced CT of the kidneys, ureters and bladder (CTKUB) is the 'gold standard' imaging investigation for establishing a diagnosis and guiding management. An appreciation of the CTKUB signs, which support or refute a diagnosis of ureteric colic, is highly valuable to the clinician when making a urological referral, and to the urologist, who must make appropriate management plans. All salient diagnostic and supportive features of ureteric colic are carefully illustrated, as are important radiological mimics, with the objectives of educating and informing the non-radiologist. Ready access to the picture archive and communication system (PACS) allows all specialists involved to interpret the radiological report with the benefit of images. A stone within the ureter may not always be readily apparent. Soft tissue rim sign around a calcific focus is an important indicator of a ureteric stone, whereas a comet tail sign suggests a phlebolith (a calcified venous thrombosis), a radiological mimic of a ureteric stone. Numerous secondary signs of ureteric obstruction may be present including hydronephrosis and perinephric stranding, and can help to confirm the diagnosis. The relative diagnostic weighting of signs is discussed, and a checklist is provided to assist with interpretation. Unexpected alternative radiological diagnoses are also illustrated, which may have significant management consequences necessitating specialist referral.

Forgotten indwelling stent in a transplanted kidney: a case report.

INTRODUCTION: Forgotten or retained ureteric stents are a well-recognised phenomenon with the potential to cause a range of complications, the most dangerous of which is obstructive nephropathy. These risks are potentially devastating when the patient has a single functioning transplanted kidney. Here we describe the case of a renal transplantation patient with a forgotten ureteric stent of 10 years, who presented with irritative bladder symptoms and was successfully managed using a multimodal urological approach with specialist advice on antibiotic prophylaxis. To the best of our knowledge this is the longest documented time period for a forgotten ureteric stent in a transplantation patient and is unusual in that obstructive nephropathy did not occur. * CASE PRESENTATION: A 32-year-old man with a history of end stage renal failure of unknown aetiology received a cadaveric renal transplant in 1995. An indwelling JJ stent was placed at the time of transplant to protect the vesicoureteric anastomosis. The patient made an unremarkable recovery and initially attended regular follow up in the renal transplant clinic. He was subsequently lost to transplant clinic follow up. In 2005 at the age of 42 he was referred to a nephrologist with irritative bladder symptoms. Renal tract imaging with ultrasound and a plain film demonstrated a retained encrusted ureteric stent. * CONCLUSION: The removal of a retained encrusted ureteric stent always provides a urological challenge. This case demonstrates that multimodal treatment involving a combination of endourological and percutaneous techniques can be employed with success even when the patient has a heavily encrusted stent for a single functioning transplanted kidney. Involvement of a microbiologist to advise on prophylactic antibiotics is deemed especially useful, as the immunosuppressed transplant patient is at particular risk of sepsis secondary to bacteraemia as a result of the endoscopic manipulation of the colonised encrusted stent. This case also provides further evidence to highlight the potential benefits of a stent registry.