UrethroNAV: the aetiology and extent of idiopathic urethral stricture in an Australian population.

Background: Lichen sclerosus (LS) is considered a causative factor in 10% of cases of idiopathic urethral stricture disease (IUSD), which is important for determining management strategies due to the underlying pathophysiology. Traditional excision urethroplasty may not be effective as inflammation often extends beyond the macroscopic stricture. This pilot study aims to answer two research questions: is LS an underlying cause of some idiopathic cause of strictures, and, if there is histological evidence suggesting predisposition of the surrounding tissue to strictures. Methods: Biopsies were taken from the stricture site as well as 1 and 2 cm proximal and distal in patients with IUSD. Histological features, including macroscopic and microscopic findings, were reported, including the presence of LS, hyperkeratosis, epidermal changes, lichenoid infiltrates, ulceration, scarring, and inflammation. Methylene blue was used to aid in locating damaged urothelium. Patients were prospectively followed up after urethroplasty. Results: From 109 urethroplasties performed between 2019 to 2022, 15 male patients were enrolled after meeting specific inclusion criteria. These criteria included a diagnosis of IUSD and the absence of any evidence of trauma, macroscopic inflammatory disease, or previous endoscopic instrumentation of the urethra. Patients had to be at least 16 years old and medically suitable for undergoing urethroplasty. The study was approved by the hospitals ethics committees. None had macroscopic evidence of LS. One patient had microscopic evidence of LS at the 2 cm proximal biopsy only. A total of 93% of patients had scarring proximal and distal to the stricture, while 20-40% had inflammatory change. The patient with microscopic LS and two inflammatory change patients had stricture recurrence after urethroplasty. Additionally, one patient with inflammatory changes was diagnosed with penile intraepithelial neoplasia (PeIN) and underwent partial penectomy. Conclusions: Findings suggest that an underlying cause of IUSD could be LS. Additionally, the pathophysiology may involve scarring and inflammation beyond the limits of the stricture with extension distal from the stricture site. Careful evaluation for concomitant urethral pathology should be considered in cases of inflammatory changes. These findings should be considered in the surgical management of IUSD and warrant further research into the role of routine biopsy and drug targets in USD.

Prognosis of Gleason score 8 prostatic adenocarcinoma in needle biopsies: a nationwide population-based study.

A 5-tier grouping of Gleason scores has recently been proposed. Studies have indicated prognostic heterogeneity within these groups. We assessed prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) for men diagnosed with Gleason score 3 + 5 = 8, 4 + 4 = 8 and 5 + 3 = 8 acinar adenocarcinoma on needle biopsy in a population-based national cohort. The Prostate Cancer data Base Sweden 5.0 was used for survival analysis with PCSM and ACM at 5 and 10 years as endpoints. Multivariable Cox regression models controlling for socioeconomic factors, stage and primary treatment type were used for PCSM and ACM. Among 199,620 men reported with prostate cancer in 2000-2020, 172,112 were diagnosed on needle biopsy. In 18,281 (11%), there was a Gleason score of 8 in needle biopsies, including a Gleason score of 3 + 5, 4 + 4 and 5 + 3 in 11%, 86% and 2.3%, respectively. The primary treatment was androgen deprivation therapy (55%), deferred treatment (8%), radical prostatectomy (16%) or radical radiotherapy (21%). PCSM in men with Gleason scores of 3 + 5, 4 + 4 and 5 + 3 at 5 years of follow-up was 0.10 (95% CI 0.09-0.12), 0.22 (0.22-0.23) and 0.32 (0.27-0.36), respectively, and at 10 years 0.19 (0.17-0.22), 0.34 (0.33-0.35) and 0.44 (0.39-0.49), respectively. There was a significantly higher PCSM after 5 and 10 years in men with Gleason score 5 + 3 cancers than in those with 4 + 4 and in Gleason score 4 + 4 cancers than in those with 3 + 5. Grouping of Gleason scores will eliminate the prognostic granularity of Gleason scoring, thus diminishing the prognostic significance of this proposed grading system.

Reinterpretation of prostate cancer pathology by Appl1, Sortilin and Syndecan-1 biomarkers.

The diagnosis of prostate cancer using histopathology is reliant on the accurate interpretation of prostate tissue sections. Current standards rely on the assessment of Haematoxylin and Eosin (H&E) staining, which can be difficult to interpret and introduce inter-observer variability. Here, we present a digital pathology atlas and online resource of prostate cancer tissue micrographs for both H&E and the reinterpretation of samples using a novel set of three biomarkers as an interactive tool, where clinicians and scientists can explore high resolution histopathology from various case studies. The digital pathology prostate cancer atlas when used in conjunction with the biomarkers, will assist pathologists to accurately grade prostate cancer tissue samples.