Exploration of Preliminary Objective Triage by Menopause Score and CA 125 Result Prior to Accelerating Fast-Track Booking for Suspected Ovarian Cancer-A Role for the Pathway Navigator?

The 28-days-to-diagnosis pathway is the current expected standard of care for women with symptoms of ovarian cancer in the UK. However, the anticipated conversion rate of symptoms to cancer is only 3%, and use of the pathway is increasing. A rapid triage at the moment of receipt of the referral might allow resources to be allocated more appropriately. In secondary care, multidisciplinary teams (MDTs) use the risk of malignancy index (RMI) score, (multiply menopausal status pre = 1 or post = 3 × ultrasound score = 0 - 3 × the CA 125 level), using a score of >200, to triage urgency and management in possible ovarian cancer cases. The most powerful determinant of the RMI score variables is CA 125 level, an objective number. Could a simple modification of the RMI score retain a high sensitivity for cancer whilst improving specificity and, consequently, decrease the morbidity of false-positive classification? To test this hypothesis, a retrospective evaluation of an ovarian two-week-wait telephone clinic of one consultant gynaecological oncologist was undertaken. Enquiry re menopause status was scored as one for pre- and three for postmenopausal or uncertain. CA 125 levels of >67 u/mL for premenopausal and >23 u/mL for postmenopausal women were used to precipitate urgent cross-sectional imaging requests and MDT opinions. These CA 125 cut thresholds were calculated using an assumption that the RMI imaging score, regardless of whether the result was available, could be three. We contemplate that women who did not exceed a provisional RMI score of >200 might be informed they are extremely unlikely to have cancer, removed from the malignancy tracker and appropriate follow-up arranged. One hundred and forty consecutive cases were analysed; 43% were deemed premenopausal and 57% postmenopausal. Twenty of the women had cancer, eighteen (90%) of whom had an RMI > 200. One hundred and twenty were benign, and only twenty-three (19%) classified as urgent cases in need of accelerated referral to imaging. In contrast, CA 125 > 35 u/mL, whilst retaining the sensitivity of 90%, misclassified 36 (30%) of the benign cases. It is possible that a telephone triage via a questionnaire determining menopausal status and the CA 125 result could offer a sensitivity for cancer of 90% and urgent expert review of under 20% of benign cases. This rapid initial telephone assessment could be presented by a trained pathway navigator, physician associate or nurse specialist. Substantial savings in NHS cancer services resources, anxieties all around and reduced patient morbidity may occur as a result.

Tumour Versus Germline BRCA Testing in Ovarian Cancer: A Single-Site Institution Experience in the United Kingdom.

The aim of this audit was to evaluate the usefulness and serviceability of testing for pathogenic mutations in BRCA1 or BRCA2 (BRCA1/2) genes in ovarian cancer (OC) patients. One hundred and thirty-five patients with more common histological sub-types of OC were retrospectively identified between 2011 and 2019. The fail rate of the molecular analysis was 7.4% (10/135). One hundred and twenty-five records were evaluated: 99 (79.2%) patients had wild-type BRCA (both somatic and germline); tumour BRCA1/2 (tBRCA1/2) pathogenic mutations were found in 20 (16%) patients with distribution between BRCA1 and BRCA2 being 40% and 60%, respectively; 13 (10.4%) patients with pathogenic variants had germline mutations; and tBRCA1/2 with variant of unknown significance (VUS), in the absence of pathogenic BRCA1 or BRCA2 variants, was detected in 6 (4.8%) patients. Our data show that expanding the molecular service to the routine first-tumour testing for patients with OC will potentially increase the detection rate of BRCA mutations, thereby providing early benefits of PARP inhibitors therapy. The tumour testing service should continue to be offered to newly diagnosed patients with high-grade epithelial cancers, including high-grade serous carcinoma, but also with carcinosarcomas and poorly-differentiated metastatic adenocarcinomas of unknown origin.

Endocervicoscopy and Biopsy to Detect Cervical Intraepithelial Squamous Neoplasia in Nonvisible Squamocolumnar Junction With Unsatisfactory Colposcopy: A Pilot Study.

The aim of this study was to investigate the practical utility of endocervicoscopy and targeted biopsy in high-risk human papilloma virus-positive women with abnormal squamous cells on cervical cytology and unsatisfactory colposcopy with nonvisible squamocolumnar junction. Seventy-seven high-risk human papilloma virus-positive patients with abnormal cervical cytology for squamous cells bearing type 3 transformation zone were enrolled. Endoscopic examination of the endocervical epithelium, with office-based continuous-flow hysteroscopy after application of acetic acid 5%, followed by targeted biopsies and consequent large loop excision of the transformation zone was carried out. Sensitivity, specificity, positive predictive value and negative predictive value of endocervicoscopy, and orientated biopsy were confronted with the results of large loop excision of the transformation zone (referral test). The sensitivity and specificity of endocervicoscopy and orientated biopsy for low-grade cervical intraepithelial neoplasia were 53% and 81%, respectively, while the sensitivity and specificity for high-grade cervical intraepithelial neoplasia were 64% and 47%, respectively. The positive predictive value for low-grade cervical intraepithelial neoplasia was 64% and for high-grade cervical intraepithelial neoplasia was 88%. The negative predictive value for low-grade cervical intraepithelial neoplasia was 87% and for high-grade cervical intraepithelial neoplasia was 41%. Endocervicoscopy is a safe, office-based technique. It is a reliable method to detect the transformation zone in patients with type 3 transformation zone and unsatisfactory colposcopy. It potentially allows target biopsy of the transformation zone but presents a relatively low specificity/negative predictive value to predict high-grade cervical intraepithelial neoplasia, thus negative biopsy results should be interpreted with caution.

A longitudinal analysis of parenting practices, couple satisfaction, and child behavior problems.

This longitudinal study examined the relationship between couple relationship satisfaction, parenting practices, parent depression, and child problem behaviors. The study participants (n = 148) were part of a larger experimental study that examined the effectiveness of a brief family-centered intervention, the Family Check-Up model. Regression analysis results indicated that our proposed model accounted for 38% of the variance in child problem behavior at Time 2, with child problem behavior and couple relationship satisfaction at child age 2 years each accounting for a significant portion of the variance in child problem behavior at age 3. Couple relationship satisfaction directly predicted child behavior problems over time. Clinical and research implications are discussed.

Prevention of tamoxifen induced endometrial polyps using a levonorgestrel releasing intrauterine system long-term follow-up of a randomised control trial.

OBJECTIVES: In a RCT, we have previously shown that the levonorgestrel intrauterine system (LNG-IUS, Mirena) produces a decidual response protecting the endometrium at one year follow-up. We here report on the long-term follow-up of this group of women, to test the hypothesis that a LNG-IUS could prevent the pro-proliferative uterine responses of tamoxifen for up to 4.5 years. METHODS: A randomised-controlled trial of postmenopausal women who had taken at least one year of adjuvant tamoxifen therapy. RESULTS: One hundred twenty-two women were recruited. Nine were found to be ineligible after randomisation. The average duration of follow-up was 26.25 months (IQR 14.5-36 months) in the surveillance group and 24.2 months (IQR 13.75-32.5 months) in the LNG-IUS group. Women with LNG-IUS in situ at the time of final assessment had decidualised endometrium, and no polyps. In the surveillance group new polyps arose in 8 cases. There were 3 new polyps in the group initially randomised to LNG-IUS, one in a patient who did not have the device inserted and 2 occurred in patients following the removal of the LNG-IUS. Univariate Cox proportional hazards regression models identified only endometrial thickness at trial entry as a statistically significant variable (HR 1.12, 95% CI 1.02 to 1.22, p=0.01) for the development of polyps. CONCLUSION: This study confirms that LNG-IUS induces benign endometrial changes and prevents endometrial polyps but only during its use in women taking tamoxifen. Endometrial thickness is a risk factor for the development of polyps.