DEveloping Tests for Endometrial Cancer deTection (DETECT): protocol for a diagnostic accuracy study of urine and vaginal samples for the detection of endometrial cancer by cytology in women with postmenopausal bleeding.

From Europe PMC via Jisc Publications RouterHistory: ppub 2021-07-01, epub 2021-07-28Publication status: PublishedFunder: Wellcome TrustFunder: Department of Health; Grant(s): NIHR300650Funder: Cancer Research UK; Grant(s): C147/A25254IntroductionPostmenopausal bleeding (PMB), the red flag symptom for endometrial cancer, triggers urgent investigation by transvaginal ultrasound scan, hysteroscopy and/or endometrial biopsy. These investigations are costly, invasive and often painful or distressing for women. In a pilot study, we found that voided urine and non-invasive vaginal samples from women with endometrial cancer contain malignant cells that can be identified by cytology. The aim of the DEveloping Tests for Endometrial Cancer deTection (DETECT) Study is to determine the diagnostic test accuracy of urine and vaginal cytology for endometrial cancer detection in women with PMB.Methods and analysisThis is a multicentre diagnostic accuracy study of women referred to secondary care with PMB. Eligible women will be asked to provide a self-collected voided urine sample and a vaginal sample collected with a Delphi screener before routine clinical procedures. Pairs of specialist cytologists, blinded to participant cancer status, will assess and classify samples independently, with differences settled by consensus review or involving a third cytologist. Results will be compared with clinical outcomes from standard diagnostic tests. A sample size of 2000 women will have 80% power to establish a sensitivity of vaginal samples for endometrial cancer detection by cytology of ≥85%±7%, assuming 5% endometrial cancer prevalence. The primary objective is to determine the diagnostic accuracy of urogenital samples for endometrial cancer detection by cytology. Secondary objectives include the acceptability of urine and vaginal sampling to women.Ethics and disseminationThis study has been approved by the North West-Greater Manchester West Research Ethics Committee (16/NW/0660) and the Health Research Authority. Results will be disseminated through publication in peer-reviewed scientific journals, presentation at conferences and via charity websites.Trial registration numberISRCTN58863784

Synchronous uterine and bladder cancers detected in urine and vaginal samples by cytology

From Wiley via Jisc Publications RouterHistory: received 2021-10-16, accepted 2021-11-02, pub-electronic 2021-11-16Article version: VoRPublication status: PublishedFunder: Medical Research Council; Id: http://dx.doi.org/10.13039/501100007155; Grant(s): MR/M018431/1Funder: National Institute for Health Research; Id: http://dx.doi.org/10.13039/501100000272; Grant(s): DRF‐2018‐11‐ST2‐054, IS‐BRC‐1215‐20007, NIHR‐CS‐012‐009Abstract: Novel diagnostics for uterine cancer are urgently needed to reduce the burden of invasive testing for the majority of healthy women with postmenopausal bleeding. We have previously shown that uterine cancer cells can be detected by cytology in urine and vaginal samples with high diagnostic accuracy. Here, we demonstrate its potential to distinguish malignant cells of different aetiologies in the same urogenital biofluid sample according to their distinctive morphology and immunoprofiles. Synchronous tumours of the urogenital tract are uncommon but can cause diagnostic confusion, delays and poor outcomes. A 79‐year‐old woman presented to accident and emergency with postmenopausal bleeding. Voided urine and Delphi screener‐collected vaginal samples were assessed by cytology and immunocytochemistry. Two malignant cell populations with distinct morphology and immunophenotypes consistent with synchronous uterine and urothelial tumours were identified. Subsequent routine diagnostics confirmed concurrent uterine carcinosarcoma and high‐grade urothelial carcinoma of the bladder. This case demonstrates that cytology and adjunctive immunocytochemistry can simultaneously identify and phenotype cancers of different aetiologies from a single urogenital biofluid sample. This can help rationalise diagnostic pathways in complex, unusual cases of dual urogenital primaries

Unsatisfactory rates vary between cervical cytology samples prepared using ThinPrep and SurePath platforms: a review and meta-analysis

Article deposited according to the BMJ Group policy for BMJ Open: http:// group.bmj.com/group/rights-licensing/permissions/authorreprints, August 21, 2012.YesFunding provided by the Open Access Authors Fund

MCM-2 CELL BASED ASSAY IS A SENSITIVE AND SPECIFIC TEST FOR RISK STRATIFICATION OF BLADDER CANCER PATIENTS.

INTRODUCTION AND OBJECTIVESCystoscopy remains the gold standard in the investigation of haematuria and follow up of patients diagnosed with the urothelial carcinoma (UC) of the bladder. There has been extensive research into identifying urinary markers with the aim of improving diagnostic accuracy. Minichromosome maintenance 2 protein (MCM2) is a marker of cell proliferation and ectopic expression is a characteristic feature of malignancy and pre-malignancy.Here we evaluate diagnostic accuracy of MCM2 in diagnosis and surveillance of UC.METHODSA feasibility study was conducted on 176 patients and healthy volunteers from 3 centres in the UK from Cystoscopic Surveillance (CS) and Gross Haematuria (GH) clinics. The verification set comprised 149 volunteers. SurePath platform was used to process the urine cytology samples. Immunocytochemical analysis of MCM2 was performed as a marker for presence of UC. Feasibility data sets were used to determine MCM2 threshold for GH and CS counts using the optimised Youden’s Index (J) and optimal sensitivity, establishing conditions such that there was a zero false negative rate. Cut-off values were used to determine sensitivity, specificity, PPV and NPV.RESULTSUsing optimised J-approach, the feasibility sets for GH and CS samples yielded cut-offs of 130 and 81 MCM2 stained cells per slide respectively.The zero false negative approach yielded cut-offs of 44 and 13 MCM2 stained cells for GH and CS patients respectively.Optimised J cut-off yielded sensitivities of 81% in CS group in feasibility and 92.3% in validation with specificities of 80.3 and 94.1% respectively. Corresponding NPV and PPVs ranged from 94.2-96% and 73.9-75.0%. GH sensitivity by optimised J was 87.5 in feasibility and 70.8% in validation sets. Specificities were 92.6 and 95.8% respectively. NPVs were 97.7 and 76.7%, PPVs were 77.8 and 94.4%. Using zero false negative level for cut-off yielded sensitivities close to 100% across all sets, albeit with a concomitant loss of specificity.CONCLUSIONSMCM2 is a reliable non-invasive test, potentially useful in diagnosis of primary and recurrent UC. MCM2 may be used to stratify cases where there is no likelihood of disease i.e. zero false negatives, thus avoiding invasive intervention. In this setting false positives are acceptable as the intervention occurs anyway: the stratification aims to reduce intervention for a large subset of true negatives, resulting in huge health economic benefits plus reduction to morbidity and discomfort associated with flexible cystosco