Faculty Bibliography

OBJECTIVE: To generate a high-resolution map of periprostatic somatic nerves. Periprostatic nerves are at risk of injury during radical prostatectomy; this study aimed to establish the location of somatic nerves with respect to the prostate and the neurovascular bundle. MATERIALS AND METHODS: Hemiprostates from patients in whom a wide local excision was performed were evaluated. Representative sections from the base, midzone, and apex of the prostate were stained with Masson's trichrome and antineuronal nitric oxide synthase antibodies, to identify myelinated and parasympathetic nerves, respectively. Somatic nerves were identified as neuronal nitric oxide synthase negative myelinated nerves. Stained slides were scanned (40x objective) for digital analysis. Location of nerves was described with reference to 6 equal sectors per hemiprostate. RESULTS: Somatic nerves account for almost 5% of all nerve fibers in the periprostatic tissue. This study found a mean somatic nerve count of 5.83, 5.25, and 3.67 at the level of the prostate base, midzone, and apex, respectively. These nerves are most frequently located either anteriorly or in the region of the neurovascular bundle (posterolateral). CONCLUSION: Somatic nerves in the periprostatic region are at risk of injury during radical prostatectomy. Further research is required to clarify their functional relevance.

Smokers develop metastatic prostate cancer more frequently than nonsmokers, suggesting that a tobacco-derived factor is driving metastatic progression. To identify smoking-induced alterations in human prostate cancer, we analyzed gene and protein expression patterns in tumors collected from current, past, and never smokers. By this route, we elucidated a distinct pattern of molecular alterations characterized by an immune and inflammation signature in tumors from current smokers that were either attenuated or absent in past and never smokers. Specifically, this signature included elevated immunoglobulin expression by tumor-infiltrating B cells, NF-kappaB activation, and increased chemokine expression. In an alternate approach to characterize smoking-induced oncogenic alterations, we also explored the effects of nicotine in human prostate cancer cells and prostate cancer-prone TRAMP mice. These investigations showed that nicotine increased glutamine consumption and invasiveness of cancer cells in vitro and accelerated metastatic progression in tumor-bearing TRAMP mice. Overall, our findings suggest that nicotine is sufficient to induce a phenotype resembling the epidemiology of smoking-associated prostate cancer progression, illuminating a novel candidate driver underlying metastatic prostate cancer in current smokers. Cancer Res; 76(5); 1055-65. (c)2015 AACR.

We describe flexible ureteroscopy-directed retrograde nephrostomy access using a puncture wire to achieve renal access. This is a natural extension of modern retrograde intrarenal surgical techniques and a modernization of the original Lawson technique for retrograde nephrostomy tract creation. In appropriately selected patients, this approach is safe and permits reduced radiation exposure. We believe this technique is easy to learn and may overcome the difficult learning curve of antegrade nephrostomy techniques faced by urologists who have not undergone subspecialty training in endourology.

We previously reported that miR-1 is among the most consistently down-regulated miRs in primary human prostate tumors. In this follow-up study, we further corroborated this finding in an independent data set and made the novel observation that miR-1 expression is further reduced in distant metastasis and is a candidate predictor of disease recurrence. Moreover, we performed in vitro experiments to explore the tumor suppressor function of miR-1. Cell-based assays showed that miR-1 is epigenetically silenced in human prostate cancer. Overexpression of miR-1 in these cells led to growth inhibition and down-regulation of genes in pathways regulating cell cycle progression, mitosis, DNA replication/repair and actin dynamics. This observation was further corroborated with protein expression analysis and 3'-UTR-based reporter assays, indicating that genes in these pathways are either direct or indirect targets of miR-1. A gene set enrichment analysis revealed that the miR-1-mediated tumor suppressor effects are globally similar to those of histone deacetylase inhibitors. Lastly, we obtained preliminary evidence that miR-1 alters the cellular organization of F-actin and inhibits tumor cell invasion and filipodia formation. In conclusion, our findings indicate that miR-1 acts as a tumor suppressor in prostate cancer by influencing multiple cancer-related processes and by inhibiting cell proliferation and motility.

OBJECTIVE: * To describe six steps for haemostasis and collecting system closure ('six degrees of haemostasis') that are reproducible and that minimize the two most concerning complications of laparoscopic partial nephrectomy: haemorrhage and urine leakage. METHODS: * A retrospective study of 23 consecutive laparoscopic partial nephrectomy cases performed by a single surgeon between 2005 and 2008 using the 'six degrees of haemostasis' was carried out. RESULTS: * There were no cases of intraoperative, postoperative or delayed bleeding. * There were no cases of urine leakage. CONCLUSION: * The 'six degrees of haemostasis' technique for laparoscopic partial nephrectomy described in the present study provides a reliable and reproducible method to reassure the surgeon of haemostasis and provide a decreased risk of urine leakage.