Pelvic Exenteration for the Treatment of Locally Advanced Vulvar Cancer in South West Wales.

The treatment of locally advanced vulvar carcinoma (LAVC) represents a major challenge. We investigated the role of pelvic exenteration as a treatment of LAVC. Women who underwent pelvic exenteration for primary and recurrent LAVC in our centre between 2001 and 2019 were included. Among the 19 women included during the study period, 14 women (73.7%) had primary LAVC while 5 women (26.3%) had recurrent disease. Surgical resection margins were microscopically clear (R0) in 94.7% of patients-14/14 undergoing primary treatment and 4/5 undergoing treatment for recurrent disease. Complete closure of the wound was achieved in 100% of women, with no wound left to heal by secondary intention. Tumour size was a predictor of requiring myocutaneous flap reconstruction, with all tumours less than 40 mm undergoing primary closure, while almost all tumours 40 mm diameter or greater (14/15 women) required flap reconstruction (p = 0.001). The 30-day major morbidity rate was 42% and there was no perioperative death. The mean overall survival was 144.8 months (2-206 months), with 1-, 2- and 5-year survival rates of 89.5%, 75.1% and 66.7%, respectively. In our centre, a primary surgical approach to the management of LAVC has resulted in good survival outcomes with acceptable morbidity rates.

Establishing a national high fidelity cadaveric emergency urology simulation course to increase trainee preparedness for independent on-call practice: a prospective observational study.

BACKGROUND: Whilst competence in the management of a wide range of urological emergencies is a requirement for certification in urology, many conditions are uncommon and exposure during training may be limited. This prospective observational study sought to evaluate the feasibility and effectiveness of a standardised cadaveric emergency urology simulation course aimed at improving operative confidence and competence prior to independent on-call practice in the United Kingdom. METHODS: A two-day cadaveric emergency urology simulation course supported by the British Association of Urological Surgeons (BAUS) was implemented at two pilot centres. All delegates that undertook one of the initial series of courses were invited to complete online pre- and post-course questionnaires relating to prior operative experience, documented competence and perceived confidence in being able to perform specific emergency procedures independently. Primary outcome was a self-reported 'confidence score' selected from a linear numeric scale ranging from 1 (not at all confident to perform a given procedure independently) to 10 (fully confident). Statistical analysis was undertaken using SPSS Statistics for Mac Version 25 and the paired student's t-test used to compare mean pre- and post-course scores. RESULTS: One hundred and four delegates undertook the course during the study period. Of these, 85 (81.7%) completed the pre-course survey and 67 (64.4%) completed the post-course survey, with 61 (58.7%) completing both. The greatest proportion of respondents were Speciality Trainees in Urology of ST5 level or higher (equivalent of Resident/Fellows with 4 or more years of surgical training; n = 31, 36.5%). Delegates reported variable pre-course exposure, with most experience reported in loin approach to the kidney (median 10) and least in exploration and packing of a transurethral resection cavity and emergency nephrectomy (median 0). Following course completion, a statistically significant increase in confidence score was observed for each procedure, with the greatest increases seen for shunt for priapism (4.87 to 8.80, p < 0.001), ureteric reimplantation (3.52 to 7.33, p < 0.001) and primary ureteric anastomosis (3.90 to 7.49, p < 0.001). CONCLUSIONS: A standardised high fidelity cadaveric simulation course is feasible and significantly improves the confidence of trainees in performing a wide range of emergency procedures to which exposure is currently limited.

A role for STEAP2 in prostate cancer progression.

Prostate adenocarcinoma is the second most frequent cancer worldwide and is one of the leading causes of male cancer-related deaths. However, it varies greatly in its behaviour, from indolent non-progressive disease to metastatic cancers with high associated mortality. The aim of this study was to identify predictive biomarkers for patients with localised prostate tumours most likely to progress to aggressive disease, to facilitate future tailored clinical treatment and identify novel therapeutic targets. The expression of 602 genes was profiled using oligoarrays, across three prostate cancer cell lines: CA-HPV-10, LNCaP and PC3, qualitatively identifying several potential prognostic biomarkers. Of particular interest was six transmembrane epithelial antigen of the prostate (STEAP) 1 and STEAP 2 which was subsequently analysed further in prostate cancer tissue samples following optimisation of an RNA extraction method from laser captured cells isolated from formalin-fixed paraffin-embedded biopsy samples. Quantitative analysis of STEAP1 and 2 gene expression were statistically significantly associated with the metastatic cell lines DU145 and PC3 as compared to the normal prostate epithelial cell line, PNT2. This expression pattern was also mirrored at the protein level in the cells. Furthermore, STEAP2 up-regulation was observed within a small patient cohort and was associated with those that had locally advanced disease. Subsequent mechanistic studies in the PNT2 cell line demonstrated that an over-expression of STEAP2 resulted in these normal prostate cells gaining an ability to migrate and invade, suggesting that STEAP2 expression may be a crucial molecule in driving the invasive ability of prostate cancer cells.

Robotic or open radical cystectomy, which is safer? A systematic review and meta-analysis of comparative studies.

UNLABELLED: Robotic radical cystectomy (RRC) has been growing in popularity across the world as a treatment option for bladder cancer. OBJECTIVES: To compare early surgical outcomes for RRC and open radical cystectomy (ORC) with an emphasis on complications and postoperative mortality rates. EVIDENCE ACQUISITION: A literature review was conducted from 2000 to 2013, including studies comparing RRC and ORC. The main outcome measures analyzed were the complications and mortality rates, in addition to patient demographics, pathological parameters, operating time, estimated blood loss (EBL), transfusion rates, and type of urinary diversion. A meta-analysis was conducted. For continuous data, the Mantel-Haenszel chi-square test was used, and for dichotomous data, inverse variance was used and each expressed as risk ratio with 95% CI. RESULTS: In total, 748 patients were included, 461 patients in the robotic group and 287 patients in the open group (seven studies). There were no significant differences in the demographic parameters of the two groups, except for age (age: p=0.03). There was no difference in the number of muscle-invasive diseases: p=0.47. No difference in positive surgical margin rates (p=0.21). PRIMARY OUTCOMES: The overall (p=0.32) and lower grade (Clavien I-II) (p=0.10) complication rates between the two cohorts did not achieve statistical significance. The high-grade (Clavien III-IV) (p=0.007) complication rates in the ORC group were significantly higher. The mortality rate (Clavien V) was higher in the ORC group (2.2%) compared with the RRC group (0.35%) and this did achieve statistical significance on a meta-analysis (p=0.04). SECONDARY OUTCOMES: The EBL and transfusion rates were statistically significantly lower in the RRC cohort (p<0.00001). The operating time was statistically significantly higher in the RRC cohort (p<0.00001). There was no statistically significant difference in the margin positivity between the two cohorts (p=0.08). CONCLUSION: In early experience, RRC appears to be feasible and a safe alternative to the ORC. RRC appears to have lower high-grade complications and mortality rates compared with the open approach. Although these results are promising, the authors would suggest caution while interpreting these results due to concerns with methodological flaws in the included studies in this review.

Putative prognostic epithelial-to-mesenchymal transition biomarkers for aggressive prostate cancer.

Prostate cancer is the second most frequently diagnosed cancer worldwide and is the sixth leading cause of cancer deaths in men, yet it varies greatly in its aggressiveness. Currently, it is not possible to adequately differentiate between patients whose tumors will remain indolent and those patients whose disease will progress, resulting in unnecessary aggressive treatment. Consequently, there is an urgent need to identify markers of prostate cancer progression, invasiveness and metastasis to more accurately predict prognosis. The aim of this study was to assess the ability of key epithelial-to-mesenchymal transition molecules in identifying prostate cancer patients who are likely to develop aggressive tumors. Using 215 archival patient tissue samples, immunohistochemistry was applied to examine the expression and sub-cellular localization of E-Cadherin, Snail, Slug, Twist, Vimentin, BMP-2 and BMP-7. Of the seven markers assessed, a significantly increased expression of Snail protein was observed within the nucleus of prostate cancer cells and was strongly associated with increasing Gleason score and clinical stage. In addition, loss of E-Cadherin expression at the cellular membrane of prostate cancer cells was also significantly associated with increasing Gleason score, clinical stage, and additionally, a reduction in survival.