Evaluation of FRAX® score use in Maltese osteoporosis management guidelines

Objectives: Recent years have brought a shift towards evidence-based fracture risk engines. Fracture Risk Assessment Tool (FRAX®) is one such diagnostic tool used to evaluate the ten-year probability of osteoporotic fracture risk. The aim of this study was to evaluate the Maltese FRAX® score-based osteoporosis management guidelines and identify the suitability of using such a risk factor engine-based protocol. Study design: Data from 702 patients presenting for bone mineral density (BMD) estimation in 2010- 2011 were collected. In this period, local guidelines were devised but not yet put into practice so all referred patients underwent BMD estimation. These patients were below 65 years of age and above the minimum age for FRAX® use: 40 years. Data included Age, Weight, Height, BMI and the presence of any risk factor components of the FRAX® score tool. BMD was assessed using Norland/Hologic densitometers. FRAX® scores (excluding BMD) for each patient were calculated using the online tool www.shef.ac.uk/FRAX as accessed in 2014. The resulting major osteoporotic fracture risk was compared to age-specific assessment thresholds as set by Kanis et al. (2013). Thus the appropriateness (or otherwise) of densitometry measurements as dictated by local guidelines was determined. Main outcome measures: The main outcome measures in this study were the femoral neck and vertebral body BMD. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of using the FRAX®-based guidelines in under 65 year olds were calculated. Results: Local guidelines for managing <65 year olds were found to have a PPV of 11.26% and a NPV of 94.38 % Conclusion: FRAX®-guided local guidelines are well suited at excluding non-osteoporotic patients (False omission rate of 5.62 %). Positive likelihood ratio for the protocol was found to be 1.27. This means that 1 in every 8.8 patients that would have been referred for BMD estimation were actually osteoporotic.peer-reviewe

Optimal gestational age for delivery in uncomplicated dichorionic twin pregnancies : a population-based study

Objectives: To identify the optimal gestational age for delivery in uncomplicated dichorionic twin pregnancies. Study Design: A retrospective analysis of gestational age-specific neonatal morbidity and mortality data was performed for 254 uncomplicated dichorionic twin pregnancies. Outcome measures included 1st and 5th minute Apgar scores, NICU admission, RDS, TTN, sepsis, seizure, hyperbilirubinemia, hypoglycaemia, neonatal length of hospital stay, birthweight and overall outcome. After correcting for confounding variables by regression analysis, adverse variable trends were assessed in each of the gestational-age- at-birth groups. Results: A significant drop in the incidence of LBW, RDS, TTN and hypoglycaemia, accompanied with the lowest NICU admission rate and neonatal length of hospital stay occurred concordantly at 38 completed weeks of gestation. The incidence of severe hyperbilirubinemia requiring phototherapy decreased significantly by 36 weeks. No correlation was found between advancing gestation and foetal, perinatal or neonatal mortality. Conclusion: Elective delivery in uncomplicated dichorionic twin pregnancies should be delayed until at least 38 completed weeks of gestation as this significantly reduces neonatal morbidity with no impact on mortality.peer-reviewe

Assessing the see-and-treat approach for the management of high-grade squamous intraepithelial cervical lesions

Objectives: To assess local histological outcomes in patients with HSIL cytology results on cervical smears, in both the see-and-treat and three-step approach. Study Design: A retrospective analysis of patients with HSIL on cervical cytology was performed, obtaining an 83 patient cohort. The histological result following the primary investigation (colposcopic-directed biopsy or excisional procedure) was noted for each patient together with their demographic variables and HPV status. Results: Of 83 patients with HSIL cytology on cervical smear, 43 underwent LLETZ as a primary procedure, while 40 patients underwent a colposcopic-directed biopsy. There was no statistically significant difference in terms of dermographics and HPV status between the two groups. In those patients who had LLETZ as a primary procedure, 29 had CIN2+ on histology. On the other hand, following colposcopic-directed biopsies, 17 resulted in CIN2+ on histology. Conclusion: The conventional approach within our local setting potentially has inferior sensitivity in picking up CIN2+ lesions when compared to the see-and-treat approach. On the other hand, primary excisional procedures were associated with an overtreatment rate of at least 20.9%, subjecting patients to unnecessary risks. Local improvement of colposcopic skill will aid to reduce this overtreatment rate and missed lesions at biopsy.peer-reviewe

Omentectomy in endometrial cancer : an evidence-based insight

Omentectomy is the surgical removal of the omentum. It is a routine component of staging surgery for confirmed or suspected ovarian carcinoma; however there is currently no consensus regarding omentectomy in surgery performed for endometrial cancer. Additionally, the extent of omental resection in patients without macroscopic deposits is unclear. A systematic search of PubMed MEDLINE resources was performed using the MeSH terms ‘endometrium’ ‘uterus’ ‘omentum’ ‘surgery’ ‘neoplasms’, and ‘neoplasm metastasis’. The authors conducted a literature review of articles published through January 2016 to summarize the current evidence analyzing omental assessment in endometrial cancer and the repercussions its involvement could have on patient management and prognosis. Metastasis to the omentum is a significant finding in endometrial cancer cases as it indicates upstaging to Stage IV-B (FIGO 2009). Assessment for omental spread helps indicate whether neoplastic deposits are spread beyond the conventional radiotherapy field and assist decision-taking with regards to platinum therapy. Macroscopic assessment of the omentum at the time of abdominal surgery for endometrial carcinoma has been shown to be highly sensitive and specific, and thus advisable. Omental biopsies and histopathological examination are more likely to affect management planning in cases at high-risk of upstaging, these being poorly differentiated tumors (Grade 2 and above), non-endometroid cytologies, cases with > 50% myometrial invasion, or cervical or adnexal involvement of the tumor. Total omentectomy and thorough histological assessment is superior with regards to detection of neoplastic spread however presents a significant strain on hospital laboratory services. Maximal surgical cytoreduction including omentectomy has been shown to improve overall survival in Stage 3 or 4 patients with good performance status.peer-reviewe

Charting the endometrial cancer care pathway : a baseline audit

Introduction: Longer waiting times from diagnosis to surgical resection have been found to negatively impact the overall survival and quality of life of women with endometrial cancer. The Cancer Care Pathway Directorate adopted the UK National Waiting Times Monitoring Dataset Guidance, to improve the timeliness of services along the cancer care pathway. From this, three key targets were identified: 1) Maximum 14-day wait from urgent GP referral for suspected cancer to first outpatient attendance (operational standard of 93%), 2) Maximum 31-day wait from decision to treat to first definitive treatment (operational standard of 96%), and 3) Maximum 62-day wait from urgent GP referral for suspected cancer to first treatment (operational standard of 85%). The aim of this baseline audit was to chart the time-frames of the various stages in the endometrial cancer pathway of patients diagnosed with this disease between 2015 and 2016 to assess for and identify delays in referral, investigation and care. -- Methods: A tool was developed following consultation with key stakeholders. Data protection clearance was obtained. Patient medical and oncology files, hospital databases, and MDT documentation for confirmed endometrial cancer cases were reviewed between September 2017 – March 2018. -- Results: A total of 101 endometrial cancer cases were included in the audit. The proportion of cases which met the 14-day, 31-day and 62-day wait KPIs operational standards were 39.1%, 81.2% and 17.2% respectively. -- Conclusion: The endometrial cancer care pathway timeframes did not meet the KPIs operational standards. Fast-track coordinators and nurse navigators could improve continuity and coordination of patient care.peer-reviewe

Clomifene citrate or low-dose FSH for the first-line treatment of infertile women with anovulation associated with polycystic ovary syndrome : a prospective randomized multinational study

BACKGROUND: Clomifene citrate (CC) is accepted as the first-line method for ovulation induction (OI) in patients with polycystic ovary syndrome (PCOS) associated with infertility owing to anovulation. Low-dose FSH has been reserved for women failing to conceive with CC. In this RCT, we tested the hypothesis that pregnancy rate (PR) and live birth rates (LBR) are higher after OI with low-dose FSH than with CC as first-line treatment. METHODS: Infertile women (<40 years old) with PCOS-related anovulation, without prior OI treatment, attending 10 centres in Europe/South America were randomized to OI with either CC (50-150 mg/day for 5 days) or FSH (starting dose 50 IU) for up to three treatment cycles. The primary outcome was clinical PR. RESULTS: Patients (n = 302) were randomized to OI with FSH (n = 132 women; 288 cycles) or CC (n = 123; 310 cycles). Per protocol analysis revealed that reproductive outcome was superior after OI with FSH than with CC with respect to PR per first cycle [30 versus 14.6%, respectively, 95 confidence interval (CI) 5.3-25.8, P = 0.003], PR per woman, (58 versus 44% of women, 95% CI 1.5-25.8, P = 0.03), LBR per woman (52 versus 39%, 95% CI 0.4-24.6, P = 0.04), cumulative PR (52.1 versus 41.2%, P = 0.021) and cumulative LBR (47.4 versus 36.9%, P = 0.031), within three cycles of OI. CONCLUSIONS: Pregnancies and live births are achieved more effectively and faster after OI with low-dose FSH than with CC. This result has to be balanced by convenience and cost in favour of CC. FSH may be an appropriate first-line treatment for some women with PCOS and anovulatory infertility, particularly older patients.peer-reviewe

Ovarian granulosa cell tumor : a clinicopathological series

Introduction: Granulosa cell tumours (GCT) are uncommon neoplasms, accounting for 2-5% of all ovarian carcinomas. The pathogenesis of these tumours is characterised by differentiation towards the follicular granulosa cell. However, the exact cell of origin is disputed, with the granulosa cell, thecal cell or fibroblast having been proposed as putative progenitors. A granulosa stem-cell has been described, which has also been suggested as a cell of origin. Approximately 65% of patients are postmenopausal at the time of diagnosis and, in these patients, the morphology of the tumour conforms to the so-called adult-type GCT. A minority of tumours, however, present at a younger age, and these tumours typically exhibit juvenile-type GCT morphology. However, this is by no means a pathological dogma and both tumour forms have been described at any age. This case series includes all cases of ovarian GCT diagnosed at Mater Dei Hospital, Malta, between 2008 and 2016. GCT cases were identified through the hospital histopathological records after the appropriate data protection clearance. This case series aims to showcase the variable natural history and presenting features of juvenile-type and adult-type GCTs, while emphasising the need for indefinite long-term follow up protocols.peer-reviewe

Mismatch repair protein expression defects in endometrioid endometrial adenocarcinoma

Objectives: Endometrioid endometrial carcinoma (EEC) is the sentinel cancer in over half female patients with heritable mismatch repair (MMR) mutations as part of Lynch syndrome. Immunohistochemical testing for tumoural MMR-protein expression is the primary screening test identifying cases potentially harbouring familial cancer syndrome-related mutations and is also a predictive biomarker for immune-checkpoint blockade response.Methods: Following Data Protection and Ethical clearance by the University of Malta, 200 EEC cases were retrospectively identified and categorized into three arms: 151 cases above age 50 at diagnosis, 49 cases at or below age 50 at diagnosis and 30 controls with benign endometrial tissue sampling. H&E case slides were re-examined by an independent pathologist to confirm the diagnosis and identify the block best representing the tumour. Four new slides per case were recut and immunohistochemistry performed for MLH1, PMS2, MSH2, and MSH6 proteins. Protein expression was analysed semiquantitatively using Allred scoring.Results: 31% of the overall EEC cases were deficient for one or more MMR-proteins. Dual loss of the MLH1-PMS2 protein heterodimer was the most common deficiency, occurring in 24.5% of cases. Loss of MSH2-MSH6 protein expression represented 3.2% of MMR-deficient cases. Well differentiated tumours had a 76.5% proficiency rate as opposed to grade 2/3 disease with 53.2% and 52.9% proficiency rate respectively. There was no significant difference in MMR status when age 50 was used as a hypothetical testing threshold. After correcting for tumour grade, MLH1 and PMS2 expression was shown to be negatively correlated with age-at-diagnosis while MSH6 expression was positively correlated.Conclusion: Reflex MMR proficiency testing of all EEC cases is advisable, as using age 50 as a testing threshold would have missed 82.3% of MMR deficient cases. Prospective evidence is required to clarify the role semi-quantitative scoring plays in MMR status interpretation and patient management in the ever-evolving field of targeted therapeutics.peer-reviewe

GYNOCARE Update: Modern Strategies to Improve Diagnosis and Treatment of Rare Gynecologic Tumors—Current Challenges and Future Directions

More than 50% of all gynecologic tumors can be classified as rare (defined as an incidence of ≤6 per 100, 000 women) and usually have a poor prognosis owing to delayed diagnosis and treatment. In contrast to almost all other common solid tumors, the treatment of rare gynecologic tumors (RGT) is often based on retrospective studies, expert opinion, or extrapolation from other tumor sites with similar histology, leading to difficulty in developing guidelines for clinical practice. Currently, gynecologic cancer research, due to distinct scientific and technological challenges, is lagging behind. Moreover, the overall efforts for addressing these challenges are fragmented across different European countries and indeed, worldwide. The GYNOCARE, COST Action CA18117 (European Network for Gynecological Rare Cancer Research) programme aims to address these challenges by creating a unique network between key stakeholders covering distinct domains from concept to cure: basic research on RGT, biobanking, bridging with industry, and setting up the legal and regulatory requirements for international innovative clinical trials. On this basis, members of this COST Action, (Working Group 1, “Basic and Translational Research on Rare Gynecological Cancer”) have decided to focus their future efforts on the development of new approaches to improve the diagnosis and treatment of RGT. Here, we provide a brief overview of the current state of-the-art and describe the goals of this COST Action and its future challenges with the aim to stimulate discussion and promote synergy across scientists engaged in the fight against this rare cancer worldwide

The First Post-Kepler Brightness Dips of KIC 8462852

We present a photometric detection of the first brightness dips of the unique variable star KIC 8462852 since the end of the Kepler space mission in 2013 May. Our regular photometric surveillance started in 2015 October, and a sequence of dipping began in 2017 May continuing on through the end of 2017, when the star was no longer visible from Earth. We distinguish four main 1%-2.5% dips, named Elsie, Celeste, Skara Brae, and Angkor, which persist on timescales from several days to weeks. Our main results so far are as follows: (i) there are no apparent changes of the stellar spectrum or polarization during the dips and (ii) the multiband photometry of the dips shows differential reddening favoring non-gray extinction. Therefore, our data are inconsistent with dip models that invoke optically thick material, but rather they are in-line with predictions for an occulter consisting primarily of ordinary dust, where much of the material must be optically thin with a size scale ≪1 μm, and may also be consistent with models invoking variations intrinsic to the stellar photosphere. Notably, our data do not place constraints on the color of the longer-term secular dimming, which may be caused by independent processes, or probe different regimes of a single process