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BackgroundProstate 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.MethodsIn 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.ResultsThe 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.ConclusionsAn 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 registrationThe trial was registered with the U.S. National Institutes of Health (NIH) Clinical Trials Registry (ClinicalTrials.gov identifier NCT02390063).

Our initial experience supports previous reports that MINI PCNL is safe and effective for the management of renal stones in children.

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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.