A multiparametric magnetic resonance imaging-based virtual reality surgical navigation tool for robotic-assisted radical prostatectomy.

OBJECTIVE: Increased computational power and improved visualization hardware have generated more opportunities for virtual reality (VR) applications in healthcare. In this study, we test the feasibility of a VR-assisted surgical navigation system for robotic-assisted radical prostatectomy. MATERIAL AND METHODS: The prostate, all magnetic resonance imaging (MRI) visible tumors, and important anatomic structures like the neurovascular bundles, seminal vesicles, bladder, and rectum were contoured on a multiparametric MRI using an in-house segmentation software. Three-dimensional (3-D) VR models were rendered and evaluated in a side room of the operating room. While interacting with the VR platform, a real-time stereo video capture of the in situ prostate was obtained to render a second 3-D model. The MRI-based model was then overlaid on the real-time model by using an automated alignment algorithm. RESULTS: Ten patients were included in this study. All MRI-based VR models were examined by surgeons immediately prior to surgery and at important steps where visualization of the tumors and their proximity to surrounding anatomic structures were critical. This was mainly during the preparation of the prostatic pedicles, neurovascular plexus, the apex, and bladder neck. All participants found the system useful, especially for tumors with locally aggressive growth patterns. For small and centrally located tumors, the system was not considered beneficial due to lack of integration into the robotic console. A fully integrated system with real-time overlays within the robotic stereo viewer was found to be the ideal scenario. CONCLUSION: We deployed a preliminary VR-assisted surgical navigation tool for robotic-assisted radical prostatectomies.

Successful Treatment of Estrogen Excess in Primary Bilateral Macronodular Adrenocortical Hyperplasia with Leuprolide Acetate.

Primary bilateral macronodular adrenocortical hyperplasia (PBMAH) is an uncommon cause of adrenal Cushing syndrome (CS) in which cortisol and occasionally other steroid hormones can be secreted under the influence of aberrantly expressed G-protein coupled receptors (GPCRs) in the adrenal cortex. We describe the unique case of a 64-year-old postmenopausal female with PBMAH whose adrenal lesions expressed luteinizing hormone receptors (LHr). She presented initially with CS and underwent right adrenalectomy; a few years later she presented with macromastia and mastodynia, possibly due to estrogen excess from her remaining left adrenocortical masses. Testing before and after treatment with quarterly leuprolide acetate therapy and immunohistochemistry on tissue and targeted sequencing of the genes of interest were performed. Tissue from the patient's right adrenal was tested for P450 aromatase (CYP19A1) and LHr expression; both were expressed throughout the hyperplastic cortex, although expression was more intense in the adenomatous areas. Targeted sequencing revealed a pathogenic PDE11A mutation, as well as variants in the ARMC5 and INHA genes. PDE11A expression was decreased in the adenoma but there was no loss of heterozygosity for the PDE11A locus. Because of the clinical presentation and LHr expression, quarterly leuprolide acetate therapy was started. Shortly after initiation of therapy, the patient reported decreased breast size and pain; she remains well controlled to date, after 10 years of treatment. This is the first description of a patient with PBMAH presenting with severe macromastia and mastodynia from what appears to be excess estrogen production from her adrenal tumor. The patient had a long-lasting response to chronic leuprolide acetate treatment, showing that drug therapy exploiting the aberrant receptor expression in PBMAH is possible even in the absence of cortisol overproduction.

The glycolytic shift in fumarate-hydratase-deficient kidney cancer lowers AMPK levels, increases anabolic propensities and lowers cellular iron levels.

Inactivation of the TCA cycle enzyme, fumarate hydratase (FH), drives a metabolic shift to aerobic glycolysis in FH-deficient kidney tumors and cell lines from patients with hereditary leiomyomatosis renal cell cancer (HLRCC), resulting in decreased levels of AMP-activated kinase (AMPK) and p53 tumor suppressor, and activation of the anabolic factors, acetyl-CoA carboxylase and ribosomal protein S6. Reduced AMPK levels lead to diminished expression of the DMT1 iron transporter, and the resulting cytosolic iron deficiency activates the iron regulatory proteins, IRP1 and IRP2, and increases expression of the hypoxia inducible factor HIF-1α, but not HIF-2α. Silencing of HIF-1α or activation of AMPK diminishes invasive activities, indicating that alterations of HIF-1α and AMPK contribute to the oncogenic growth of FH-deficient cells.