Proteomic Analysis of Prostate Cancer FFPE Samples Reveals Markers of Disease Progression and Aggressiveness.

Prostate cancer (PCa) is the second most common cancer in men. Diagnosis and risk assessment are widely based on serum Prostate Specific Antigen (PSA) and biopsy, which might not represent the exact degree of PCa risk. Towards the discovery of biomarkers for better patient stratification, we performed proteomic analysis of Formalin Fixed Paraffin Embedded (FFPE) prostate tissue specimens using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Comparative analysis of 86 PCa samples among grade groups 1-5 identified 301 significantly altered proteins. Additional analysis based on biochemical recurrence (BCR; BCR+ n = 14, BCR- n = 51) revealed 197 significantly altered proteins that indicate disease persistence. Filtering the overlapping proteins of these analyses, seven proteins (NPM1, UQCRH, HSPA9, MRPL3, VCAN, SERBP1, HSPE1) had increased expression in advanced grades and in BCR+/BCR- and may play a critical role in PCa aggressiveness. Notably, all seven proteins were significantly associated with progression in Prostate Cancer Transcriptome Atles (PCTA) and NPM1NPM1, UQCRH, and VCAN were further validated in The Cancer Genome Atlas (TCGA), where they were upregulated in BCR+/BCR-. UQCRH levels were also associated with poorer 5-year survival. Our study provides valuable insights into the key regulators of PCa progression and aggressiveness. The seven selected proteins could be used for the development of risk assessment tools.

Reed Miller Nesbit: Broadening the Horizon of Genitourinary Surgery.

Nesbit has made his name synonymous with transurethral prostate resection and attained eminence by popularizing his technique, although his lifetime achievements and contributions reach many aspects of genitourinary surgery and pediatric urology. We believe our history article will bring memories back to more senior urologists, allow the youngsters to recall a true innovator and versatile surgeon, and appeal to a broad audience such as the readership of Surgical Innovation Journal.

Total Osseous Calcification of the Prostate Gland.

Prostatic calculi are commonly seen in older men as their incidence increases with age. They are associated with prostate hypertrophy, chronic inflammation of the gland, prostate cancer, and rarely with other pathological conditions such as granulomatous diseases. Although typical small in size, they can seldom become giant and replace the entire prostate gland with only few cases reported in literature. We present one such rare case of a young male who presented to the emergency department with clinical manifestations of sepsis and no relevant past medical history. The patient was ultimately treated with open simple retropubic prostatectomy as a surgical stone extraction method.

Laparoscopic and Robotic Management of Ureteral Stricture in Adults.

BACKGROUND/AIM: The aim of this review was to provide an update on the status of minimal invasive treatment of ureteral stricture either with a laparoscopic or robotic surgery. MATERIALS AND METHODS: Eligible studies, published until November 2019 were retrieved through Medline, Cochrane and Pubmed databases. Predetermined inclusion and exclusion criteria were used as selection method for data synthesis and acquisition. The study was performed in accordance with the PRISMA statement. RESULTS: A total of 19 retrospective studies met the inclusion criteria. All of them demonstrated the safety, feasibility and success of both laparoscopic and robotic ureteral reconstruction. Individual case series or cumulative comparison analysis of the available studies showed at least equivalent success rates and a trend favoring laparoscopic and robotic groups in terms of estimated blood loss and length of hospital stay to the detriment of longer operative times and possibly higher cost. CONCLUSION: Current evidence suggests the effectiveness, safety and increasing incorporation of minimally invasive techniques for complex stricture repair and reconstruction.

Prostatosymphyseal Fistula After Photoselective Vaporization of the Prostate: A Very Rare Complication of a Transurethral Surgery.

Prostatosymphyseal fistula (PSF) is a very rare complication described after transurethral surgery of the prostate including photoselective vaporization of the prostate (PVP) with GreenLightΤΜ laser (Boston Scientific, Marlborough, MA). Sporadic cases have also been reported in the literature as side effects of pelvic radiation therapy. We present a 65-year-old male patient who underwent PVP as an elective procedure for the treatment of severe lower urinary tract symptoms. The primary management after the diagnosis of the fistula was conservative but as this did not result in an expected improvement, the patient underwent radical prostatectomy as a last resort. PSF formation is the result of the communication between the anterior capsule of the prostate and the bladder neck via pubic symphysis and the surrounding tissues. This condition often leads to either urinoma formation or osteitis pubis. In the majority of cases, treatment options are complex surgical reconstruction using flaps or grafts, radical prostatectomy or urinary diversion as an ultimate solution. The rarity of the complication and the accompanied atypical signs and symptoms warrant a low threshold for suspicion so as to diagnose the event early and provide the appropriate treatment.

Proteomics Analysis of Formalin Fixed Paraffin Embedded Tissues in the Investigation of Prostate Cancer.

Prostate cancer (PCa) is one of the leading causes of death in men worldwide. The molecular features, associated with the onset and progression of the disease, are under vigorous investigation. Formalin-fixed paraffin-embedded (FFPE) tissues are valuable resources for large-scale studies; however, their application in proteomics is limited due to protein cross-linking. In this study, the adjustment of a protocol for the proteomic analysis of FFPE tissues was performed which was followed by a pilot application on FFPE PCa clinical samples to investigate whether the optimized protocol can provide biologically relevant data for the investigation of PCa. For the optimization, FFPE mouse tissues were processed using seven protein extraction protocols including combinations of homogenization methods (beads, sonication, boiling) and buffers (SDS based and urea-thiourea based). The proteome extraction efficacy was then evaluated based on protein identifications and reproducibility using SDS electrophoresis and high resolution LC-MS/MS analysis. Comparison between the FFPE and matched fresh frozen (FF) tissues, using an optimized protocol involving protein extraction with an SDS-based buffer following beads homogenization and boiling, showed a substantial overlap in protein identifications with a strong correlation in relative abundances (rs = 0.819, p < 0.001). Next, FFPE tissues (3 sections, 15 µm each per sample) from 10 patients with PCa corresponding to tumor (GS = 6 or GS ≥ 8) and adjacent benign regions were processed with the optimized protocol. Extracted proteins were analyzed by GeLC-MS/MS followed by statistical and bioinformatics analysis. Proteins significantly deregulated between PCa GS ≥ 8 and PCa GS = 6 represented extracellular matrix organization, gluconeogenesis, and phosphorylation pathways. Proteins deregulated between cancerous and adjacent benign tissues, reflected increased translation, peptide synthesis, and protein metabolism in the former, which is consistent with the literature. In conclusion, the results support the relevance of the proteomic findings in the context of PCa and the reliability of the optimized protocol for proteomics analysis of FFPE material.

First case of complete bladder duplication in the coronal plane with concomitant duplication of the urethra in an adult male.

Duplication of the lower urinary tract is a very rare congenital anomaly which is diagnosed either at birth or during early childhood. These rare malformations are most of the times accompanied by other concomitant anomalies and are therefore diagnosed immediately after birth. In some even rarer cases there are no concomitant anomalies and symptoms thus leading to a diagnosis later in childhood. This is the first case in the literature of complete bladder duplication in the coronal plane with concomitant duplication of the urethra and no other associated anomalies in a 52-year-old male who remained asymptomatic and therefore undiagnosed for more than 5 decades.