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AimTo examine the effects of specialist reporting on error rates in prostate core biopsy diagnosis.MethodBiopsies were reported by eight specialist uropathologists over 3 years. New cancer diagnoses were double-reported and all biopsies were reviewed for the multidisciplinary team (MDT) meeting. Diagnostic alterations were recorded in supplementary reports and error rates were compared with a decade previously.Results2600 biopsies were reported. 64.1% contained adenocarcinoma, a 19.7% increase. The false-positive error rate had reduced from 0.4% to 0.06%. The false-negative error rate had increased from 1.5% to 1.8%, but represented fewer absolute errors due to increased cancer incidence.ConclusionsSpecialisation and double-reporting have reduced false-positive errors. MDT review of negative cores continues to identify a very low number of false-negative errors. Our data represents a ‘gold standard’ for prostate biopsy diagnostic error rates. Increased use of MRI-targeted biopsies may alter error rates and their future clinical significance.

An increasing volume of prostate biopsies and a worldwide shortage of urological pathologists puts a strain on pathology departments. Additionally, the high intra-observer and inter-observer variability in grading can result in overtreatment and undertreatment of prostate cancer. To alleviate these problems, we aimed to develop an artificial intelligence (AI) system with clinically acceptable accuracy for prostate cancer detection, localisation, and Gleason grading. We digitised 6682 slides from needle core biopsies from 976 randomly selected participants aged 50–69 in the Swedish prospective and population-based STHLM3 diagnostic study done between May 28, 2012, and Dec 30, 2014 (ISRCTN84445406), and another 271 from 93 men from outside the study. The resulting images were used to train deep neural networks for assessment of prostate biopsies. The networks were evaluated by predicting the presence, extent, and Gleason grade of malignant tissue for an independent test dataset comprising 1631 biopsies from 246 men from STHLM3 and an external validation dataset of 330 biopsies from 73 men. We also evaluated grading performance on 87 biopsies individually graded by 23 experienced urological pathologists from the International Society of Urological Pathology. We assessed discriminatory performance by receiver operating characteristics and tumour extent predictions by correlating predicted cancer length against measurements by the reporting pathologist. We quantified the concordance between grades assigned by the AI system and the expert urological pathologists using Cohen's kappa. The AI achieved an area under the receiver operating characteristics curve of 0·997 (95% CI 0·994–0·999) for distinguishing between benign (n=910) and malignant (n=721) biopsy cores on the independent test dataset and 0·986 (0·972–0·996) on the external validation dataset (benign n=108, malignant n=222). The correlation between cancer length predicted by the AI and assigned by the reporting pathologist was 0·96 (95% CI 0·95–0·97) for the independent test dataset and 0·87 (0·84–0·90) for the external validation dataset. For assigning Gleason grades, the AI achieved a mean pairwise kappa of 0·62, which was within the range of the corresponding values for the expert pathologists (0·60–0·73). An AI system can be trained to detect and grade cancer in prostate needle biopsy samples at a ranking comparable to that of international experts in prostate pathology. Clinical application could reduce pathology workload by reducing the assessment of benign biopsies and by automating the task of measuring cancer length in positive biopsy cores. An AI system with expert-level grading performance might contribute a second opinion, aid in standardising grading, and provide pathology expertise in parts of the world where it does not exist. Swedish Research Council, Swedish Cancer Society, Swedish eScience Research Center, EIT Health.

Normal migrating cells exhibit contact inhibition of locomotion (CIL) when meeting a neighbouring cell, but metastatic cancer cells lose this inhibition. Interactions btween ephrin and ephrin receptors are now shown to underlie CIL in migrating cells. Metastatic cancer cells typically fail to halt migration on contact with non-cancer cells. This invasiveness is in contrast to normal mesenchymal cells that retract on contact with another cell. Why cancer cells are defective in contact inhibition of locomotion is not understood. Here, we analyse the dynamics of prostate cancer cell lines co-cultured with fibroblasts, and demonstrate that a combinatorial code of Eph receptor activation dictates whether cell migration will be contact inhibited. The unimpeded migration of metastatic PC-3 cells towards fibroblasts is dependent on activation of EphB3 and EphB4 by ephrin-B2, which we show activates Cdc42 and cell migration. Knockdown of EphB3 and EphB4 restores contact inhibition of locomotion to PC-3 cells. Conversely, homotypic collisions between two cancer cells results in contact inhibition of locomotion, mediated by EphA–Rho–Rho kinase (ROCK) signalling. Thus, the migration of cancer cells can switch from restrained to invasive, depending on the Eph-receptor profile of the cancer cell and the reciprocal ephrin ligands expressed by neighbouring cells.

Sparing the periprostatic neurovascular bundles during robot-assisted radical prostatectomy (RARP) improves postoperative erectile function and early urinary continence recovery. The NeuroSAFE technique, a standardised frozen section analysis, enables accurate real-time detection of positive surgical margins during nerve-sparing, increasing the likelihood of successful nerve preservation. However, the impact of the technique on patient outcomes remains uncertain. We aimed to assess the effect of NeuroSAFE-guided RARP versus standard RARP on erectile function and urinary continence. NeuroSAFE PROOF was a multicentre, patient-blinded, randomised, controlled phase 3 trial done at five National Health Service hospitals in the UK. Key eligibility criteria were a diagnosis of non-metastatic prostate cancer deemed suitable to undergo RARP, good erectile function (defined as a score of ≥22 on the first 5 items of the International Index of Erectile Function [IIEF]) without medical erectile function assistance, and no previous prostate cancer treatment. No age limits were applied. Participants were randomly assigned (1:1) to standard RARP or NeuroSAFE-guided RARP using block randomisation, stratified by site. Masking of participants to allocation was maintained throughout, but patients were informed of their nerve-sparing status after the operation. Due to the nature of the intervention, operating teams were aware of treatment group. Nerve-sparing was guided by a preoperative plan in the standard RARP group and by intraoperative NeuroSAFE assessment in the NeuroSAFE group. The primary outcome was erectile function at 12 months, assessed using the IIEF-5 score, in the modified intention-to-treat population, which included all randomly assigned participants who had surgery. Secondary endpoints were urinary continence scores at 3 and 6 months, evaluated using the International Consultation on Incontinence Questionnaire (ICIQ), and the erectile function domain of the IIEF (IIEF-6) scores at 12 months. The trial is registered at ClinicalTrials.gov, NCT03317990. Between Jan 6, 2019, and Dec 6, 2022, 407 patients were recruited, of whom 381 had surgery (190 participants in the NeuroSAFE group and 191 participants in the standard RARP group), and were included in the modified intention-to-treat population. Data for the primary outcome (IIEF-5 score at 12 months) were available for 344 participants (173 in the NeuroSAFE group and 171 participants in the standard RARP group). Median follow-up was 12·3 months (IQR 11·8–12·7). At 12 months, the mean IIEF-5 score was 12·7 (SD 8·0) in the NeuroSAFE group versus 9·7 (7·5) in the standard RARP group (adjusted mean difference 3·18 [95% CI 1·62 to 4·75]; p<0·0001). At 3 months, the ICIQ score was significantly lower in the NeuroSAFE group than the standard RARP group (adjusted mean difference –1·41 [95% CI –2·42 to –0·41]; p=0·006). At 6 months, no significant difference in ICIQ score was observed between groups (adjusted mean difference –0·37 [95% CI –1·35 to 0·62]; p=0·46). At 12 months, the mean IIEF-6 score was higher in the NeuroSAFE group than in the standard RARP group (15·3 [SD 9·7] vs 11·5 [SD 9·0]; adjusted mean difference 3·92 [95% CI 2·01 to 5·83]; p<0·0001). Serious adverse events occurred in six (3%) of 190 patients in the NeuroSAFE group, and and in five (3%) of 191 patients in the standard RARP group. All adverse events were postoperative complications; no serious adverse events or deaths were attributed to the study intervention. The use of NeuroSAFE to guide nerve-sparing during RARP improves patient-reported IIEF-5 scores at 12 months and short-term urinary continence. The erectile function benefit is enhanced in patients who would not otherwise have undergone bilateral nerve-sparing by standard practice. National Institute of Healthcare Research, JP Moulton Charitable Foundation, UCLH Charity, St Peters Trust, and Rosetrees Trust.

AimTo determine how clinicians use data in contemporary prostate biopsy reports.MethodsA survey was circulated to members of the British Association of Urological Surgeons and the British Uro-oncology Group.ResultsResponses were received from 114 respondents (88 urologists, 26 oncologists). Ninety-seven (94%) use the number of positive cores from each side and 43 (42%) use the % number of positive cores. When determining the number and percentage of positive cores, 72 (71%) would not differentiate between targeted and non-targeted samples. If multiple Gleason Scores (GS) were included in a report, 77 (78%) would use the worst GS even if present in a core with very little tumour, 12% would use the global GS and 10% the GS in the core most involved by tumour. Fifty-five (55%) either never or rarely used perineural invasion for patient management.ConclusionsThe number of positive cores is an important parameter for patient management but may be difficult to determine in the laboratory due to core fragmentation so the biopsy taker must indicate the number of biopsies obtained. Multiple biopsies taken from a single site are often interpreted by clinicians as separate cores when determining the number of positive cores so pathologists should also report the number of sites positive. Clinicians have a non-uniform approach to the interpretation of multiple GS in prostate biopsy reports so we recommend that pathologists also include a single ‘bottom-line’ GS for each case to direct the clinician’s treatment decision.

The International Collaboration on Cancer Reporting (ICCR) was formed in 2011 to harmonise the datasets, protocols and checklists for pathological reporting of various cancers and develop internationally agreed upon, evidence-based datasets. A dataset for prostate cancer in radical prostatectomy specimens was developed in 2011–2012 as part of a pilot project; however, it required substantial revision following the ISUP Consensus Conference on Gleason Grading in 2014, the publication of the World Health Organisation (WHO) Classification of Tumours of the Urinary System and Male Genital Organs in 2016, and the 8th edition of the Tumour-Node-Metastasis (TNM) staging system in late 2016. This article presents the up-to-date, evidence-based ICCR dataset and associated commentary for reporting prostate cancer in radical prostatectomy specimens. PubMed and Google search engines were used to review the published literature on the subject, and the dataset was developed in line with the previously published ICCR framework for the development of cancer datasets. Substantial changes have been incorporated into the second edition of the ICCR prostate cancer (radical prostatectomy) dataset. These include revisions to prostate cancer grading, reporting of intraductal carcinoma of prostate and surgical margins, among others. Up-to-date cancer datasets underpin structured reporting and facilitate the production of consistent and accurate pathological data for patient care as well as comparisons between different cohorts and populations internationally.

Background Robotic radical prostatectomy (RARP) is a first-line curative treatment option for localized prostate cancer. Postoperative erectile dysfunction and urinary incontinence are common associated adverse side effects that can negatively impact patients’ quality of life. Preserving the lateral neurovascular bundles (NS) during RARP improves functional outcomes. However, selecting men for NS may be difficult when there is concern about incurring in positive surgical margin (PSM) which in turn risks adverse oncological outcomes. The NeuroSAFE technique (intra-operative frozen section examination of the neurovascular structure adjacent prostate margin) can provide real-time pathological consult to promote optimal NS whilst avoiding PSM. Methods NeuroSAFE PROOF is a single-blinded, multi-centre, randomised controlled trial (RCT) in which men are randomly allocated 1:1 to either NeuroSAFE RARP or standard RARP. Men electing for RARP as primary treatment, who are continent and have good baseline erectile function (EF), defined by International Index of Erectile Function (IIEF-5) score > 21, are eligible. NS in the intervention arm is guided by the NeuroSAFE technique. NS in the standard arm is based on standard of care, i.e. a pre-operative image-based planning meeting, patient-specific clinical information, and digital rectal examination. The primary outcome is assessment of EF at 12 months. The primary endpoint is the proportion of men who achieve IIEF-5 score ≥ 21. A sample size of 404 was calculated to give a power of 90% to detect a difference of 14% between groups based on a feasibility study. Oncological outcomes are continuously monitored by an independent Data Monitoring Committee. Key secondary outcomes include urinary continence at 3 months assessed by the international consultation on incontinence questionnaire, rate of biochemical recurrence, EF recovery at 24 months, and difference in quality of life. Discussion NeuroSAFE PROOF is the first RCT of intra-operative frozen section during radical prostatectomy in the world. It is properly powered to evaluate a difference in the recovery of EF for men undergoing RARP assessed by patient-reported outcome measures. It will provide evidence to guide the use of the NeuroSAFE technique around the world. Trial registration NCT03317990 (23 October 2017). Regional Ethics Committee; reference 17/LO/1978.

Abstract Introduction: Reactive angioendotheliomatosis (RAE) is a rare, benign, angioproliferative disorder with poorly understood aetiopathogenesis. It is characterised by vascular occlusion that occurs in patients with coexistent systemic or autoimmune disease. Case Presentation: A 60-year-old female presented with an 8-week history of a painful, non-healing, and non-traumatic ulcer on the left thigh. Her past medical history included smoking, peripheral vascular disease (PVD) and previously treated rectal squamous cell carcinoma. The diagnosis of pyoderma gangrenosum with superimposed cellulitis was considered and treatment with oral antibiotics was initiated. Following failure to improve, a biopsy was undertaken leading to the diagnosis of RAE. The patient was referred for urgent consideration of surgical correction of PVD, but was deemed unsuitable for surgical treatment due to a poor performance status. The patient was treated with conservative measures, but her condition rapidly deteriorated and she passed away a few weeks later. Conclusion: RAE is notorious for mimicking a wide spectrum of diseases. It is an important differential diagnosis to consider in patients with non-healing ulceration and underlying systemic or autoimmune disorders. Our case raises awareness of this rare condition and the mortality that it carries if left untreated. In an attempt to reverse disease progression and mortality, we urge clinicians to attempt surgical correction of PVD even when faced with multiple comorbidities and poor performance status.

Introduction: Mycobacterium marinum was first described in humans in 1954, known to infect fish species and contaminate water and fish products. Inoculation to humans occurs through injured skin resulting in the formation of a solitary nodule known as “fish tank granuloma.” Disseminated infections have been reported in the immunocompromised and can present with extracutaneous manifestations such as arthritis and osteomyelitis. Nonaquatic transmission has not been previously reported. Case Presentation: A 63‐year‐old lady with rheumatoid arthritis and bronchiectasis was referred to dermatology with widespread soft dermal plaques, pustules, erosions, and necrotic wounds. Multiple bacterial and viral swabs were negative. A biopsy was performed that showed a neutrophilic dermatosis suggestive of Sweet’s Syndrome. The patient initially improved with prednisolone, but subsequently deteriorated with a worsening rash, joint pains, and neutropenic sepsis. Repeat biopsies eventually revealed abundant acid‐fast bacilli, later confirmed to be Mycobacterium marinum . Our patient had no history of exposure to aquatic organisms but had previously cared for an inland bearded dragon with an unknown illness. Although infection with M. marinum has been reported in reptiles, cases of nonaquatic zoonotic transmission have not been described in the literature. Conclusion: Mycobacterium marinum infection should be considered in patients with indicative clinical and histological features, especially in the immunocompromised, even in the absence of an obvious aquatic source of infection. Awareness of this entity could lead to earlier diagnoses and reduced morbidity and mortality.