The PROFILE Feasibility Study: Targeted Screening of Men With a Family History of Prostate Cancer.

BACKGROUND: A better assessment of individualized prostate cancer (PrCa) risk is needed to improve screening. The use of the prostate-specific antigen (PSA) level for screening in the general population has limitations and is not currently advocated. Approximately 100 common single nucleotide polymorphisms (SNPs) have been identified that are associated with the risk of developing PrCa. The PROFILE pilot study explored the feasibility of using SNP profiling in men with a family history (FH) of PrCa to investigate the probability of detecting PrCa at prostate biopsy (PB). The primary aim of this pilot study was to determine the safety and feasibility of PrCa screening using transrectal ultrasound-guided PB with or without diffusion-weighted magnetic resonance imaging (DW-MRI) in men with a FH. A secondary aim was to evaluate the potential use of SNP profiling as a screening tool in this population. PATIENTS AND METHODS: A total of 100 men aged 40-69 years with a FH of PrCa underwent PB, regardless of their baseline PSA level. Polygenic risk scores (PRSs) were calculated for each participant using 71 common PrCa susceptibility alleles. We treated the disease outcome at PB as the outcome variable and evaluated its associations with the PRS, PSA level, and DW-MRI findings using univariate logistic regression. RESULTS: Of the 100 men, 25 were diagnosed with PrCa, of whom 12 (48%) had clinically significant disease. Four adverse events occurred and no deaths. The PSA level and age at study entry were associated with PrCa at PB (p = .00037 and p = .00004, respectively). CONCLUSION: The results of the present pilot study have demonstrated that PB is a feasible and safe method of PrCa screening in men with a FH, with a high proportion of PrCa identified requiring radical treatment. It is feasible to collect data on PrCa-risk SNPs to evaluate their combined effect as a potential screening tool. A larger prospective study powered to detect statistical associations is in progress. IMPLICATIONS FOR PRACTICE: Prostate biopsy is a feasible and safe approach to prostate cancer screening in men with a family history and detects a high proportion of prostate cancer that needs radical treatment. Calculating a polygenic risk score using prostate cancer risk single nucleotide polymorphisms could be a potential future screening tool for prostate cancer.

The use of high-resolution magnetic resonance imaging in the management of patients presenting with priapism.

OBJECTIVE: To investigate the use of magnetic resonance imaging (MRI) of the penis during an episode of priapism and assess the viability of the corpus cavernosum (CC) smooth muscle, as prolonged ischaemic priapism is associated with a high rate of long-term erectile dysfunction (ED), and the viability of CC smooth muscle influences the subsequent management in ischaemic priapism. PATIENTS AND METHODS: The study was set in a single centre based in a large university teaching hospital. We investigated the correlation of T2-weighted gadolinium- enhanced MRI with the histology from CC biopsies in the same patients. In all, 38 patients (mean age 42 years) presenting with priapism over a 3-year period had MRI of the penis. The scans were reported by two dedicated uro-radiologists who graded the MR images as showing viable or nonviable erectile tissue. One pathologist assessed the CC biopsies for necrosis. The findings were then correlated. Where no biopsies were taken a clinical follow-up was used to assess erectile function. RESULTS: In 23 patients undergoing both a CC biopsy and MRI, the sensitivity of MRI in predicting nonviable smooth muscle was 100%. In a further 10 patients MRI showed nonviable CC smooth muscle, but no biopsy was taken in these patients; on clinical follow-up all of these patients subsequently developed ED. In a further five patients the imaging showed viable smooth muscle and these patients subsequently maintained erectile function on clinical follow up. CONCLUSIONS: Penile MRI provides an accurate imaging method to assess smooth muscle viability in patients presenting with priapism.

Prostate cancer: diagnosis and staging.

Prostate cancer represents an increasing health burden. The past 20 years, with the introduction of prostate-specific antigen (PSA), has seen prostate cancer move increasingly from a condition that presented with locally advanced disease or metastases to one that is found upon screening. More is also known about the pathology of pre-malignant lesions. Diagnosis relies on trans-rectal ultrasound (TRUS) to obtain biopsies from throughout the prostate, but TRUS is not useful for staging. Imaging for staging, such as magnetic resonance imaging or computed tomography, still has a low accuracy compared with pathological specimens. Current techniques are also inaccurate in identifying lymph node and bony metastases. Nomograms have been developed from the PSA, Gleason score and clinical grading to help quantify the risk of extra-capsular extension in radical prostatectomy specimens. Improved clinical staging modalities are required for more reliable prediction of pathological stage and for monitoring of response to treatments.

Parasitic manifestation of testicular pain.

Genital filariasis is common in endemic areas of the world. However, filariasis cannot be eliminated from the differential diagnosis of scrotal swellings, as international travel is more frequent. We report a case in a patient in London, UK.

Laparoscopic pelvic lymph node dissection allows significantly more accurate staging in "high-risk" prostate cancer compared to MRI or CT.

OBJECTIVE: To compare the accuracy of lymph node staging using pelvic MRI or CT to that of laparoscopic pelvic lymph node dissection (LPLND) in prostate cancer patients prior to radical radiotherapy. MATERIAL AND METHODS: A total of 55 consecutive patients at high risk of locally advanced disease [prostate-specific antigen (PSA) > 10 ng/ml, Gleason score 7 or worse on biopsy, normal (99m) Tc bone scan] underwent either a pelvic MRI (n = 42) or CT (n = 13) scan and subsequent LPLND. Preoperative staging was compared to the histology of the lymph node specimens obtained. RESULTS: A total of 20/55 (36.4%) patients had pelvic lymph node metastases confirmed by LPLND. MRI identified three patients (27.3%) with pelvic lymph node metastases and missed eight (72.7%) whilst CT identified none of nine patients with pelvic lymph node metastases. The groups with histologically-positive and -negative nodes had similar mean ages (63 vs 65 years; p = 0.52), Gleason scores (6.8 vs 6.5; p = 0.41) and PSA levels (43.1 vs 31.4 ng/ml; p = 0.56). CONCLUSION: The presence or absence of lymph node metastases has critical implications for the prognosis and treatment of prostate cancer. In this study both MRI and CT missed many cases of lymph node metastases in "high-risk" patients. While a positive scan seems likely to indicate nodal metastases, the low sensitivity in high-risk patients seems unacceptable if treatment decisions are to be based on accurate staging, and LPLND offers an alternative.

Reduction of TSG101 protein has a negative impact on tumor cell growth.

TSG101 was defined originally as a tumor-suppressor gene, raising the expectation that absence of the encoded protein should lead to increased tumor cell growth and, perhaps, increased tumor cell aggressiveness. We have used the RNA interference (RNAi) technique to downregulate TSG101 in PC3 (prostate cancer) and MDA-MB-231 (breast cancer) cells. An approximately 85% selective downregulation at the protein level was achieved in both cell lines over a period of 12 days as detected by Western blotting. This treatment resulted in inhibition of tumor cell growth, with a decreased level of TSG101 causing partial cell cycle arrest at the G(1)/S boundary and a reduction in the rate at which cells passed from G(2) through mitosis and back into G(1). In both cell lines, the percentage of cells in S-phase was reduced significantly at day 4 after the TSG101 siRNA transfection (27% vs. 41% in MDA-MB-231 cells; 22% vs. 39% in PC3 cells). Additionally, RNAi-mediated downregulation of TSG101 reduced the colony formation capacities of both cancer cell lines. Rather more surprisingly, TSG101 downregulation affected the migratory activity of the MDA-MB-231 cells, independent of any effect on proliferation. Thus, in a Transwell assay, after 4-hr incubation, 36.0% of control MDA-MB-231 cells had migrated to the lower chamber vs. 7.3% of TSG101-downregulated cells (p < 0.001; scrambled control, 36.5%). These results show that the TSG101 gene does not comply with the usual characteristics of a tumor-suppressor gene; rather, its expression may be necessary for activities associated with aspects of tumor progression.