NeuroSAFE in radical prostatectomy increases the rate of nerve-sparing surgery without affecting oncological outcome.

OBJECTIVES: To investigate the impact of intra-operative neurovascular structure-adjacent frozen-section examination (NeuroSAFE) on the rate of nerve-sparing surgery (NSS) and oncological outcome in a large radical prostatectomy (RP) cohort. PATIENTS AND METHODS: Between January 2016 and December 2020, 1756 prostate cancer patients underwent robot-assisted RP, of whom 959 (55%) underwent this with NeuroSAFE and 797 (45%) without (control cohort). In cases where NeuroSAFE showed tumour in the margin, a secondary resection was performed. The effect of NeuroSAFE on NSS and positive surgical margin (PSM) status was analysed using logistic regression. Cox regression was used to identify predictors of biochemical recurrence-free survival (BCRFS). RESULTS AND LIMITATIONS: Patients in the NeuroSAFE cohort had a higher tumour grade (P < 0.001) and clinical stage (P < 0.001) than those in the control cohort. NeuroSAFE enabled more frequent NSS for both pT2 (93% vs 76%; P < 0.001) and pT3 disease (83% vs 55%; P < 0.001). In adjusted analysis, NeuroSAFE resulted in more frequent unilateral (odds ratio [OR] 3.90, 95% confidence interval (CI) 2.90-5.30; P < 0.001) and bilateral (OR 5.22, 95% CI 3.90-6.98; P < 0.001) NSS. While the PSM rate decreased from 51% to 42% in patients with pT3 stage disease (P = 0.031), NeuroSAFE was not an independent predictor of PSM status (OR 0.85, 95% CI 0.68-1.06; P = 0.2) in the entire cohort. Patients who underwent NeuroSAFE had better BCRFS compared to the control cohort (hazard ratio 0.62, 95% CI 0.45-0.84; P = 0.002). This study is limited by its comparison with a historical cohort and lack of functional outcomes. CONCLUSIONS: NeuroSAFE enables more unilateral and bilateral NSS without negatively affecting surgical margin status and biochemical recurrence. This validation study provides a comprehensive overview of the implementation, evaluation and intra-operative decision making associated with NeuroSAFE in clinical practice.

Intraoperative assessment and reporting of radical prostatectomy specimens to guide nerve-sparing surgery in prostate cancer patients (NeuroSAFE).

AIMS: Radical prostatectomy for prostate cancer is frequently complicated by urinary incontinence and erectile dysfunction. Nerve-sparing surgery reduces the risk of postoperative complications and can be optimised by the use of intraoperative frozen sections of the adjacent neurovascular structure (NeuroSAFE). The aims of this study were to evaluate the pathological outcomes of the NeuroSAFE technique and to develop a comprehensive algorithm for intraoperative clinical decision-making. METHODS AND RESULTS: Between September 2018 and May 2019, 491 NeuroSAFE procedures were performed in 258 patients undergoing radical prostatectomy; 74 of 491 (15.1%) NeuroSAFE specimens had positive surgical margins. As compared with the corresponding paraffin sections, NeuroSAFE had a positive predictive value and negative predictive value of 85.1% and 95.4%, respectively. In 72.2% of secondary neurovascular bundle resections prompted by a NeuroSAFE positive surgical margin, no tumour was present. These cases more often had a positive surgical margin of ≤1 mm (48.7% versus 20.0%; P = 0.001) and only one positive slide (69.2% versus 33.3%; P = 0.008). None of the nine patients with Gleason pattern 3 at the surgical margin, a positive surgical margin length of ≤1 mm and one positive slide had tumour in the secondary resection. CONCLUSIONS: This study provides a systematic reporting template for pathological intraoperative NeuroSAFE evaluation, supporting intraoperative clinical decision-making and comparison between prostate cancer operation centres.

[A 37-year-old woman with anogenital warts]. / Een 37-jarige vrouw met anogenitale wratten.

A 37-year-old woman, who had been suffering from Crohn's disease since twenty-two years, visited our dermatology outpatient clinic with complaints of wart-like lesions in the vulvar and perianal regions. On physical examination, nodules, plaques and tumours were seen. Histological examination showed features compatible with Crohn's disease. The diagnosis metastatic Crohn's disease was made.

Transient hyperproliferation of a transgenic human epidermis expressing hepatocyte growth factor.

Hepatocyte growth factor (HGF) is a fibroblast-derived protein that affects the growth, motility, and differentiation of epithelial cells including epidermal keratinocytes. To investigate the role of HGF in cutaneous biology and to explore the possibility of using it in a tissue engineering approach, we used retroviral-mediated gene transfer to introduce the gene encoding human HGF into diploid human keratinocytes. Modified cells synthesized and secreted significant levels of HGF in vitro and the proliferation of keratinocytes expressing HGF was enhanced compared with control unmodified cells. To investigate the effects of HGF in vivo, we grafted modified keratinocytes expressing HGF onto athymic mice using acellular dermis as a substrate. When compared with controls, HGF-expressing keratinocytes formed a hyperproliferative epidermis. The epidermis was thicker, had more cells per length of basement membrane, and had increased numbers of Ki-67-positive proliferating cells, many of which were suprabasal in location. Hyperproliferation subsided and the epidermis was equivalent to controls by 2 weeks, a time frame that coincides with healing of the graft. Transient hyperproliferation may be linked to the loss of factors present in the wound that activate HGF. These data suggest that genetically modified skin substitutes secreting HGF may have applications in wound closure and the promotion of wound healing.