Renal cell carcinoma (RCC) is not a single disease, but several histologically defined cancers with different genetic drivers, clinical courses, and therapeutic responses. The current study evaluated 843 RCC from the three major histologic subtypes, including 488 clear cell RCC, 274 papillary RCC, and 81 chromophobe RCC. Comprehensive genomic and phenotypic analysis of the RCC subtypes reveals distinctive features of each subtype that provide the foundation for the development of subtype-specific therapeutic and management strategies for patients affected with these cancers. Somatic alteration of BAP1, PBRM1, and PTEN and altered metabolic pathways correlated with subtype-specific decreased survival, while CDKN2A alteration, increased DNA hypermethylation, and increases in the immune-related Th2 gene expression signature correlated with decreased survival within all major histologic subtypes. CIMP-RCC demonstrated an increased immune signature, and a uniform and distinct metabolic expression pattern identified a subset of metabolically divergent (MD) ChRCC that associated with extremely poor survival.

OBJECTIVE: To investigate the effectiveness and usability of automated procedural guidance during virtual temporal bone surgery. METHODS: Two randomised controlled trials were performed to evaluate the effectiveness, for medical students, of two presentation modalities of automated real-time procedural guidance in virtual reality simulation: full and step-by-step visual presentation of drillable areas. Presentation modality effectiveness was determined through a comparison of participants' dissection quality, evaluated by a blinded otologist, using a validated assessment scale. RESULTS: While the provision of automated guidance on procedure improved performance (full presentation, p = 0.03; step-by-step presentation, p < 0.001), usage of the two different presentation modalities was vastly different (full presentation, 3.73 per cent; step-by-step presentation, 60.40 per cent). CONCLUSION: Automated procedural guidance in virtual temporal bone surgery is effective in improving trainee performance. Step-by-step presentation of procedural guidance was engaging, and therefore more likely to be used by the participants.

Isotropic hyperelastic models have been used to determine the material properties of normal human cartilage, but there remains an incomplete understanding of how these properties may be altered by osteoarthritis. The aims of this study were to (1) measure the material constants of normal and osteoarthritic human knee cartilage using isotropic hyperelastic models; (2) determine whether the material constants correlate with histological measures of structure and/or cartilage tissue damage; and (3) quantify the abilities of two common isotropic hyperelastic material models, the neo-Hookean and Yeoh models, to describe articular cartilage contact force, area, and pressure. Small osteochondral specimens of normal and osteoarthritic condition were retrieved from human cadaveric knees and from the knees of patients undergoing total knee arthroplasty and tested in unconfined compression at loading rates and large strains representative of weight-bearing activity. Articular surface contact area and lateral deformation were measured concurrently and specimen-specific finite element models then were used to determine the hyperelastic material constants. Structural parameters were measured using histological techniques while the severity of cartilage damage was quantified using the OARSI grading scale. The hyperelastic material constants correlated significantly with OARSI grade, indicating that the mechanical properties of cartilage for large strains change with tissue damage. The measurements of contact area described anisotropy of the tissue constituting the superficial zone. The Yeoh model described contact force and pressure more accurately than the neo-Hookean model, whereas both models under-predicted contact area and poorly described the anisotropy of cartilage within the superficial zone. These results identify the limits by which isotropic hyperelastic material models may be used to describe cartilage contact variables. This study provides novel data for the mechanical properties of normal and osteoarthritic human articular cartilage and enhances our ability to model this tissue using simple isotropic hyperelastic materials.

Radical prostatectomy with preservation of the neurovascular bundles (NVB) is a treatment option for localised prostate cancer in selected patients. An interesting debate has developed about the precise technique used to preserve these nerves. The standard technique releases the NVB from the postero-lateral groove between the prostate and rectum. A new technique, dubbed the "veil of Aphrodite" technique, proposes a higher release of the lateral prostatic fascia on the presumption that cavernosal nerves exist in this area. We have reviewed the evidence for the anatomical basis of nerve-sparing radical prostatectomy, particularly with respect to the standard versus the "veil" technique of radical prostatectomy. Microdissections of the NVB in cadaveric specimens have confirmed the course of the cavernosal nerves in the postero-lateral groove between the prostate and rectum. Though studies have also demonstrated nerves higher in the lateral prostatic fascia, these are likely to innervate the prostate rather than the cavernosal tissues. Though excellent potency results have been reported for the "veil" technique from one institution, there is not sufficient anatomical evidence to support this technique over the standard technique of nerve-sparing radical prostatectomy.

We report the first case of salvage robotic-assisted laparoscopic radical prostatectomy (RALP) following failed primary high-intensity focussed ultrasound (HIFU) for localised carcinoma of the prostate. A 66-year-old male with a presenting prostate-specific antigen (PSA) of 5 ng/ml was diagnosed with T1c Gleason 3 + 4 prostate cancer. He underwent transurethral resection of the prostate and HIFU. His PSA dropped to 2.0 ng/ml and repeat biopsy revealed upgrading of his prostate cancer to Gleason 4 + 3. He was referred to us for a second opinion and, following discussion of his options, he underwent RALP. The total operative time was 159 min. There were no intra- or postoperative complications. He was discharged on postoperative day two and was fully continent 10 days following removal of his catheter. His PSA remained undetectable 6 months postoperatively. Salvage RALP was feasible in this case with good functional and short-term oncological outcomes for the patient.