Recent Submissions

  • The Role of NLRP3 Inflammasome in Obesity and PCOS—A Systematic Review and Meta-Analysis

    Atalah Alenezi, Salih; Snell, Lindsay; Aboeldalyl, Shaimaa; Amer, Saad
    Inflammasomes have recently been implicated in the pathogenesis of several chronic inflammatory disorders, such as diabetes and obesity. The aim of this meta-analysis was to investigate the possible role of the NLRP3 inflammasome in obesity and polycystic ovarian syndrome (PCOS). A comprehensive search of electronic databases was conducted to identify studies investigating NLRP3 its related components (Caspase 1, ASC and IL-1β) in adipose tissue and/or blood from obese individuals compared to non-obese controls. Another search was conducted for studies investigating NLRP3 in PCOS women and animal models. The ssearched databases included Medline, EMBASE, Cochrane Library, PubMed,, the EU Clinical Trials Register and the WHO International Clinical Trials Register. The quality and risk of bias for the included articles were assessed using the modified Newcastle–Ottawa scale. Data were extracted and pooled using RevMan software for the calculation of the standardized mean difference (SMD) and 95% confidence interval (CI). Twelve eligible studies were included in the obesity systematic review and nine in the PCOS review. Of the obesity studies, nine (n = 270) were included in the meta-analysis, which showed a significantly higher adipose tissue NLRP3 gene expression in obese (n = 186) versus non-obese (n = 84) participants (SMD 1.07; 95% CI, 0.27, 1.87). Pooled analysis of adipose tissue IL-1β data from four studies showed significantly higher IL-1β gene expression levels in adipose tissue from 88 obese participants versus 39 non-obese controls (SMD 0.56; 95% CI, 0.13, 0.99). Meta-analysis of adipose tissue ASC data from four studies showed a significantly higher level in obese (n = 109) versus non-obese (n = 42) individuals (SMD 0.91, 95% CI, 0.30, 1.52). Of the nine PCOS articles, three were human (n = 185) and six were animal studies utilizing PCOS rat/mouse models. All studies apart from one article consistently showed upregulated NLRP3 and its components in PCOS women and animal models. In conclusion, obesity and PCOS seem to be associated with upregulated expression of NLRP3 inflammasome components. Further research is required to validate these findings and to elucidate the role of NLRP3 in obesity and PCOS.
  • Fifteen-minute consultation: Approach to the infant with stridor and suspected laryngomalacia.

    Whittaker, Rachel
    Stridor in an infant is a significant clinical sign; the primary objectives are to ensure that the airway is safe and to arrange timely, appropriate management. A structured history, examination and targeted investigations will determine the cause and guide care. Laryngomalacia is the most common cause of stridor in an infant. The stridor tends to start shortly after birth, classically presenting as a positional stridor in the first month, which gradually resolves before 12-18 months of age in mild cases. There is a wide spectrum of severity; few require surgical intervention. This article will outline how the infant is appropriately assessed and managed.
  • Prediction of Surgical Outcome in Advanced Ovarian Cancer by Imaging and Laparoscopy: A Narrative Review.

    Indrielle-Kelly, T (2023-03)
    Maximal-effort upfront or interval debulking surgery is the recommended approach for advanced-stage ovarian cancer. The role of diagnostic imaging is to provide a systematic and structured report on tumour dissemination with emphasis on key sites for resectability. Imaging methods, such as pelvic and abdominal ultrasound, contrast-enhanced computed tomography, whole-body diffusion-weighted magnetic resonance imaging and positron emission tomography, yield high diagnostic performance for diagnosing bulky disease, but they are less accurate for depicting small-volume carcinomatosis, which may lead to unnecessary explorative laparotomies. Diagnostic laparoscopy, on the other hand, may directly visualize intraperitoneal involvement but has limitations in detecting tumours beyond the gastrosplenic ligament, in the lesser sac, mesenteric root or in the retroperitoneum. Laparoscopy has its place in combination with imaging in cases where ima-ging results regarding resectability are unclear. Different imaging models predicting tumour resectability have been developed as an adjunctional objective tool. Incorporating results from tumour quantitative analyses (e.g., radiomics), preoperative biopsies and biomarkers into predictive models may allow for more precise selection of patients eligible for extensive surgery. This review will discuss the ability of imaging and laparoscopy to predict non-resectable disease in patients with advanced ovarian cancer.
  • Correlation of IVF outcomes and number of oocytes retrieved: a UK retrospective longitudinal observational study of 172 341 non-donor cycles.

    Jayaprakasan, Kanna
    OBJECTIVE: How do numbers of oocytes retrieved per In vitro fertilisation (IVF) cycle impact on the live birth rate (LBR) and multiple gestation pregnancy (MGP) rates? DESIGN: Retrospective observational longitudinal study. SETTING: UK IVF clinics. POPULATION: Non-donor IVF patients. MAIN OUTCOME MEASURES: LBR per IVF cycle and MGP levels against number of oocytes retrieved into subgroups: 0, 1-5, 6-15, 16-25, 26-49 oocytes and 50+ oocytes. Relative risk (RR) and 95% CIs were calculated for each group against the intermediate responder with '6-15 oocytes collected'. RESULTS: From 172 341 attempted fresh oocyte retrieval cycles, the oocyte retrieved was: 0 in 10 148 (5.9%) cycles from 9439 patients; 1-5 oocytes in 42 574 cycles (24.7%); 6-15 oocytes in 91 797 cycles (53.3%); 16-25 oocytes in 23 794 cycles (13.8%); 26-49 oocytes in 3970 cycles (2.3%); ≥50 oocytes in 58 cycles (0.033%). The LBRs for the 1-5, 6-15, 16-25 and 26-49 subgroups of oocytes retrieved were 17.2%, 32.4%, 35.3% and 18.7%, respectively. The RR (95% CI) of live birth in comparison to the intermediate group (6-15) for 1-5, 16-25 and 26-49 groups was 0.53 (0.52 to 0.54), 1.09 (1.07 to 1.11) and 0.58 (0.54 to 0.62), respectively. The corresponding MGP rates and RR were 9.2%, 11.0%, 11.4% and 11.3%, respectively and 0.83 (0.77 to 0.90), 1.04 (0.97 to 1.11) and 1.03 (0.84 to 1.26), respectively. CONCLUSION: There was only limited benefit in LBR beyond the 6-15 oocyte group going to the 16-25 oocytes group, after which there was significant decline in LBR. The MGP risk was lower in 1-5 group.
  • Chronic ectopic pregnancy presenting as a suspected tubo-ovarian abscess: a diagnostic dilemma.

    Alao, A; Dasgupta, J; Biswas, Bivas
    Though there is no definite agreement on diagnostic criteria or definition of chronic ectopic pregnancy (CEP), it could be deemed to be a variant of pregnancy of unknown location with non-specific clinical signs and symptoms. This was a case of a para 2+2 who presented with lower abdominal pain and bleeding per vaginum, and initial ultrasound was suggestive of a tubo-ovarian abscess/mass. With a further MRI scan and a diagnostic laparoscopy, she was found to have a CEP and had a laparoscopic salpingectomy for management. The diagnosis of CEP could be quite challenging as a result of the protracted symptoms, often negative/low serum B-HCG and ultrasound features mimicking a pelvic mass. A high index of suspicion is needed, and an MRI scan and diagnostic laparoscopy often aid in diagnosis and management.
  • FARGO-360: a multi-disciplinary survey of practice and perspectives on provision of care for patients with frailty presenting with gynecological cancers in the UK and Ireland.

    Addley, Susan
    OBJECTIVES: Frailty has been associated with worse cancer-related outcomes for people with gynecological cancers. However, the lack of clear guidance on how to assess and modify frailty prior to instigating active treatments has the potential to lead to large variations in practice and outcomes. This study aimed to evaluate current practice and perspectives of healthcare practitioners on the provision of care for patients with frailty and a gynecological cancer. METHODS: Data were collected via a questionnaire-based survey distributed by the Audit and Research in Gynecological Oncology (ARGO) collaborative to healthcare professionals who identified as working with patients with gynecological malignancies in the United Kingdom (UK) or Ireland. Study data were collected using REDCap software hosted at the University of Manchester. Responses were collected over a 16 week period between January and April 2021. RESULTS: A total of 206 healthcare professionals (30 anesthetists (14.6%), 30 pre-operative nurses (14.6%), 51 surgeons (24.8%), 34 cancer specialist nurses (16.5%), 21 medical/clinical oncologists (10.2%), 25 physiotherapists/occupational therapists (12.1%) and 15 dieticians (7.3%)) completed the survey. The respondents worked at 19 hospital trusts across the UK and Ireland. Frailty scoring was not routinely performed in 63% of care settings, yet the majority of practitioners reported modifying their practice when providing and deciding on care for patients with frailty. Only 16% of organizations surveyed had a dedicated pathway for assessment and management of patients with frailty. A total of 37% of respondents reported access to prehabilitation services, 79% to enhanced recovery, and 27% to community rehabilitation teams. CONCLUSION: Practitioners from all groups surveyed considered that appropriate training, dedicated pathways for optimization, frailty specific performance indicators and evidence that frailty scoring had an impact on clinical outcomes and patient experience could all help to improve care for frail patients.
  • The prevalence of hyperprolactinaemia in subfertile ovulatory women and its impact on fertility treatment outcome.

    Amer, Saad; Jayaprakasan, Kanna
    Subtle hyperprolactinaemia is not an uncommon finding in ovulatory subfertile women. The objective of this study is to evaluate the prevalence of hyperprolactinaemia in subfertile ovulatory and oligo-anovulatory women, and to determine if hyperprolactinaemia influences fertility treatment outcome. All women (n = 1010) who attended the fertility clinic of a UK tertiary hospital during 2015-2019 were included. Out of 804 eligible women analysed, 575 women (71.5%) were ovulatory and 229 (28.5%) were oligo-anovulatory. Prevalence of hyperprolactinaemia was higher in the ovulatory group than in the oligo-anovulatory group (26.8% vs. 14.4%; OR: 2.2; 95% confidence interval (CI): 1.4-3.2). On sub-group analysis, the prevalence of mild, moderate and severe hyperprolactinaemia was 23.0%, 3.7% and 0.2% in ovulatory women and 11.8%, 1.7% and 0.9% in oligo-anovulatory women. Mild hyperprolactinaemia was found to be more prevalent in the ovulatory group (OR: 2.2; 95%CI: 1.4-3.5). Ongoing pregnancy/livebirth rates were similar between hyperprolactinaemic and normoprolactinaemic women (42.8% vs. 46.7%). Hyperprolactinaemia did not have an impact on ongoing pregnancy/livebirth rates in both ovulatory and oligo-anovulatory women (OR:0.8; 95%CI: 0.5-1.1; OR: 1.2; 95%CI: 0.6-2.5, respectively). Hyperprolactinaemia is prevalent among ovulatory women, although most had mildly raised clinically insignificant levels. Elevated prolactin levels in ovulatory women do not seem to impact on pregnancy outcome. Impact StatementWhat is already known on this subject? Prolactin has been linked to ovulation and fertility. Prolactin testing is not generally recommended for subfertile women with regular menstrual cycles, which is a surrogate marker of ovulation. However, some clinicians, particularly in the general practice, still perform prolactin test as part of baseline endocrine profile.What do the results of this study add? Prevalence of hyperprolactinaemia in subfertile ovulatory women was 26.8% (154/575), of which 86% (132/154) were mild. Further, the livebirth/ongoing pregnancy rates were similar between hyperprolactinaemic and normoprolactinaemic women. Prolactin being a sensitive hormone, responsive to even minimal stress and its high levels not influencing clinical pregnancy outcome, prolactin measurement is not needed in women having regular menstrual cycles.What are the implications of these findings for clinical practice and/or further research? Hyperprolactinaemia was not uncommon in ovulatory women, although most had mildly elevated levels. Hyperprolactinaemia did not have any impact on fertility treatment outcome. Serum prolactin should not be tested in ovulating women, as mild elevations are commonly present and have no clinical significance.
  • Global inequality in sub-fertility treatment needs safer, cost effective, evidence-based and economically viable choices for patients and stakeholders.

    Jayaprakasan, Kanna (2022-01)
    The global increase in subfertility diagnosis and treatments and the rise of private equity investors concentrating on high profits based on in vitro fertilisation (IVF) treatments raise profound societal and economic questions for stakeholders and patients. The question remains as to whose benefits will ultimately be greater when promoting high margins treatment options resulting from cross-border mergers and acquisitions of IVF clinics.This paper covers wide-ranging issues from the erroneously constructed UK National Institute for Health and Care Excellence's (NICE) guidelines on treatment choices, the cost-effectiveness of treatments, the promotion of IVF, and add-ons where evidence remains minimal, the commercial size of the fertility industry. Investment in improving intrauterine insemination (IUI) success rates has understandably been avoided for its short-term impact on the IVF industry. However, IUI efficiency would cut across many of the global subfertility treatment economic and access problems while allowing stakeholder, feepaying, and patients financial savings will likely allow for more funded IVF cycles in acutely deserving cases. The recommendations will help expand choices for globally economically challenged patients' and services while enhancing an ethical and moral dimension towards fertility treatment choices for patients and stakeholders.
  • Dehydroepiandrosterone (DHEA) role in enhancement and maintenance of implantation (DREAM): randomised double-blind placebo-controlled trial-study protocol.

    Jayaprakasan, Kanna (BMJ, 2021)
    INTRODUCTION: Dehydroepiandrosterone (DHEA) is an important precursor of androgen and has been studied and researched extensively for improving the various outcome measures of ovarian stimulation in women with advanced age or poor ovarian response. Androgens also play an important role in the enhancement of endometrial and decidual function by regulating both the transcriptome and secretome of the endometrial stromal cells and have a positive effect on various factors like insulin-like growth factor binding protein 1, homeobox genes (HOXA10, HOXA11), secreted phosphoprotein 1, prolactin which are necessary for implantation. It is well-known that the circulating 'precursor pool' of DHEA declines with age more so in poor ovarian reserve patients and exogenous supplementation may be beneficial in such cases. This double-blinded randomised controlled trial (RCT) aims to test the hypothesis whether transient targeted supplementation of DHEA as an adjuvant to progesterone in frozen embryo transfer (FET) cycles, for women with low serum testosterone, helps in improving live birth rate. METHODS AND ANALYSIS: This study is planned as a double-blinded, placebo-controlled randomised trial and the sample size, calculated for the primary outcome measure-live birth rate, is 140. All participants will be having a flexible antagonist protocol for controlled ovarian stimulation and an elective freeze-all policy for the embryos as per the hospital protocol after written informed consent. For FET, the endometrium will be prepared by hormone replacement treatment protocol. During the FET cycle, the intervention group will be receiving DHEA 25 mg two times a day for 15 days from the day of starting progesterone supplementation and the control group will be receiving a placebo. ETHICS AND DISSEMINATION: The approval of the study was granted by the Clinical Trials Registry-India and the Institutional Ethical Committee of CRAFT Hospital and Research Center. All participants will provide written informed consent before being randomised into allocated treatment groups. The results will be disseminated to doctors and patients through conference presentations, peer-reviewed publications, social media and patient information booklets. TRIAL REGISTRATION NUMBERS: CTRI/2020/06/025918; ECR/1044/Inst/KL/2018.
  • Serum Albumin as a Predictor of Survival after Interval Debulking Surgery for Advanced Ovarian Cancer (AOC): A Retrospective Study

    Phillips, A (2020-10)
    Objective: To investigate the impact of serum albumin (at diagnosis and pre-operatively) on survival in patients undergoing cytoreductive surgery for advanced ovarian cancer(AOC) and whether improvement in albumin achieved following neoadjuvant chemotherapy (NACT) affects overall survival (OS). Methods: Outcomes of 441 patients who underwent cytoreduction for AOC were reviewed. Albumin was recorded at diagnosis and pre-operatively. Further analysis was performed if patients were hypoalbuminaemic at diagnosis.Analysis was stratified according to whether the patientreceived primary debulking surgery (PDS) or interval debulking surgery (IDS) and if their albumin was corrected. Results: 308 patients had a serum albumin level at diagnosis and 400 patients had a pre-operative albumin available for analysis. For patients with an albumin at diagnosis ≤ 35g/L and ≥36 g/L, median OS was 31.5 (95% CI 23.5-39.5) and 50.4 (95% CI 38.9-61.9) months respectively (P = 0.003). Followingmultivariate analysis (MVA), albumin at diagnosis remained statistically significant as an independent marker for survival, even after adjusting for cytoreductive outcome, stage and grade(p = 0.04, Hazard ratio 1.38, 95% CI 1.01-1.89). Hypoalbuminaemic patients at diagnosis achieved complete cytoreduction in 53% of cases.For PDS patients, median OS was 19.7 months (95% CI 11.5-27.9). For IDS patients, median OS was 27.9 months (n = 1).IDS patients with a corrected albumin had a median OS of 42.9 months (95% CI 31.5-54.3) (p > 0.05). Conclusion: Hypoalbuminaemia at diagnosis is a poor prognostic factor in AOC. Normalization of serum albumin after NACT is a potential predictor of survival.
  • Skene’s Gland Derivatives in the Female Genital Tract and Cervical Adenoid Basal Carcinoma are Consistently Positive With Prostatic Marker NKX3.1

    Hawari, Rand; Fernandes, Larissa (2020-10)
    Cervical ectopic prostatic tissue and vaginal tubulosquamous polyp are rare lesions which exhibit variable, and often focal, immunohistochemical expression with traditional prostatic markers [prostate-specific antigen and prostatic acid phosphatase (PSAP)]. These lesions are thought to arise from periurethral Skene’s glands, the female equivalent of prostatic glands in the male. Adenoid basal carcinoma is a rare and indolent cervical neoplasm. Expression of the prostatic marker NKX3.1 in ectopic prostatic tissue and tubulosquamous polyp has been reported but no studies have examined immunoreactivity with this marker in adenoid basal carcinoma. We stained 19 cases [adenoid basal carcinoma (n=6), cervical ectopic prostatic tissue (n=11), and vaginal tubulosquamous polyp (n=3); 1 case contained both adenoid basal carcinoma and ectopic prostatic tissue] with NKX3.1. In all cases, the glandular component of these lesions exhibited diffuse nuclear immunoreactivity while normal endocervical glands were negative. Prostate-specific antigen was positive in 4 of 9 and 0 of 3 cases of ectopic prostatic tissue and tubulosquamous polyp, respectively, while PSAP was positive in 3 of 4 and 2 of 2 cases of ectopic prostatic tissue and tubulosquamous polyp respectively; 3 of 5 cases of adenoid basal carcinoma tested were focally positive with PSAP and all 5 were negative with prostate-specific antigen. While the specificity of NKX3.1 should be investigated in future studies, positivity with this marker may be useful in diagnosing these uncommon lesions. NKX3.1 appears a more sensitive marker of ectopic prostatic tissue and tubulosquamous polyp than traditional prostatic markers and positive staining provides further support that these lesions exhibit “prostatic” differentiation and are of Skene’s gland origin. NKX3.1 and PSAP positivity in adenoid basal carcinoma raises the possibility of an association with benign glandular lesions exhibiting prostatic differentiation and we critically discuss the possible association.
  • Observational retrospective study of UK national success, risks and costs for 319,105 IVF/ICSI and 30,669 IUI treatment cycles.

    Jayaprakasan, Kanna (2020-03)
    OBJECTIVE: To compare success rates, associated risks and cost-effectiveness between intrauterine insemination (IUI) and in vitro fertilisation (IVF). DESIGN: Retrospective observational study. SETTING: The UK from 2012 to 2016. PARTICIPANTS: Data from Human Fertilisation and Embryology Authority's freedom of information request for 2012-2016 for IVF/ICSI (intracytoplasmic sperm injection)and IUI as practiced in 319 105 IVF/ICSI and 30 669 IUI cycles. Direct-cost calculations for maternal and neonatal expenditure per live birth (LB) was constructed using the cost of multiple birth model, with inflation-adjusted Bank of England index-linked data. A second direct-cost analysis evaluating the incremental cost-effective ratio (ICER) was modelled using the 2016 national mean (baseline) IVF and IUI success rates. OUTCOME MEASURES: LB, risks from IVF and IUI, and costs to gain 1 LB. RESULTS: This largest comprehensive analysis integrating success, risks and costs at a national level shows IUI is safer and more cost-effective than IVF treatment.IVF LB/cycle success was significantly better than IUI at 11.49% (p<0.001) but the IUI success is much closer to IVF at 2.35:1, than previously considered. IVF remains a significant source of multiple gestation pregnancy (MGP) compared with IUI (RR (Relative Risk): 1.45 (1.31 to 1.60), p<0.001) as was the rate of twins (RR: 1.58, p<0.001).In 2016, IVF maternal and neonatal cost was £115 082 017 compared with £2 940 196 for IUI and this MGP-related perinatal cost is absorbed by the National Health Services. At baseline tariffs and success rates IUI was £42 558 cheaper than IVF to deliver 1LB with enhanced benefits with small improvements in IUI. Reliable levels of IVF-related MGP, OHSS (ovarian hyperstimulation syndrome), fetal reductions and terminations are revealed. CONCLUSION: IUI success rates are much closer to IVF than previously reported, more cost-effective in delivering 1 LB, and associated with lower risk of complications for maternal and neonatal complications. It is prudent to offer IUI before IVF nationally.
  • The impact of uterine artery embolization on ovarian reserve: A systematic review and meta-analysis.

    El-Shamy, Tarek; Amer, Saad; Mohamed, Ahmed; James, Cathryn; Jayaprakasan, Kanna (2020-01)
    INTRODUCTION: Uterine artery embolization (UAE) has been gaining increasing popularity as an effective and minimally invasive treatment for uterine fibroids. However, there has been growing concern over the risk of unintended embolization of the utero-ovarian circulation, leading to reduction of ovarian blood supply with subsequent impairment of ovarian reserve. The purpose of this study was to investigate the impact of UAE on circulating anti-Müllerian hormone (AMH) and other markers of ovarian reserve. MATERIAL AND METHODS: This meta-analysis included all published cohort, cross-sectional and case-control studies, as well as randomized trials that investigated the impact of UAE on circulating AMH. Data sources included MEDLINE, EMBASE, Dynamed Plus, ScienceDirect, TRIP database, and the Cochrane Library from January 2000 to June 2019. All identified articles were screened, and articles were selected based on the inclusion and exclusion criteria. AMH and other data were extracted from the eligible articles and entered into RevMan software to calculate the weighted mean difference between pre- and post-embolization values. PROSPERO registration number: CRD42017082615. RESULTS: This review included 3 cohort and 3 case-control studies (n = 353). The duration of follow up after UAE ranged between 3 and 12 months. Overall pooled analysis of all studies showed no significant effect of UAE on serum AMH levels (weighted mean difference -0.58 ng/mL; 95% CI -1.5 to 0.36, I2 = 95%). Subgroup analysis according to age of participants (under and over 40 years) and according to follow-up duration (3, 6 and 12 months) showed no significant change in post-embolization circulating AMH. Pooled analysis of serum follicle-stimulating hormone (FSH) concentrations (4 studies, n = 248) revealed no statistically significant change after UAE (weighted mean difference 4.32; 95% CI -0.53 to 9.17; I2 = 95%). Analysis of 2 studies (n = 62) measuring antral follicle count showed a significant decline at 3-month follow up (weighted mean difference -3.28; 95% CI -5.62 to -0.93; I2 = 94%). CONCLUSIONS: Uterine artery embolization for uterine fibroids does not seem to affect ovarian reserve as measured by serum concentrations of AMH and FSH.
  • The test accuracy of antenatal ultrasound definitions of fetal macrosomia to predict birth injury: A systematic review.

    Robinson, R (2020-03)
    OBJECTIVES: To determine which ultrasound measurement for predicted fetal macrosomia most accurately predicts adverse delivery and neonatal outcomes. STUDY DESIGN: Four biomedical databases searched for studies published after 1966. Randomised trials or observational studies of women with singleton pregnancies, resulting in a term birth who have undergone an index test of interest measured and recorded as predicted fetal macrosomia ≥28 weeks. Adverse outcomes of interest included shoulder dystocia, brachial plexus injury (BPI) and Caesarean section. RESULTS: Twenty-five observational studies (13,285 participants) were included. For BPI, the only significant positive association was found for Abdominal Circumference (AC) to Head Circumference (HC) difference > 50 mm (OR 7.2, 95 % CI 1.8-29). Shoulder dystocia was significantly associated with abdominal diameter (AD) minus biparietal diameter (BPD) ≥ 2.6 cm (OR 4.2, 95 % CI 2.3-7.5, PPV 11 %) and AC > 90th centile (OR 2.3, 95 % CI 1.3-4.0, PPV 8.6 %) and an estimated fetal weight (EFW) > 4000 g (OR 2.1 95 %CI 1.0-4.1, PPV 7.2 %). CONCLUSIONS: Estimated fetal weight is the most widely used ultrasound marker to predict fetal macrosomia in the UK. This study suggests other markers have a higher positive predictive value for adverse outcomes associated with fetal macrosomia.
  • Does sites of recurrence impact survival in secondary cytoreduction surgery for recurrent epithelial ovarian cancer?

    Phillips, A (2020-01)
    Outcomes of secondary cytoreduction surgery (SCS) were evaluated for morbidity, progression free survival (PFS) and overall survival (OS) and factors influencing results were explored. Retrospective analysis of all cases of SCS for epithelial ovarian cancer (EOC) was performed from October 2010 to December 2017. 62 patients were prospectively identified as candidates for SCS and 57 underwent SCS. 20(35%) patients required bowel resection/s, 24(42%) had nodal resections and 11(19%) had extensive upper abdominal surgery. 51(89%) achieved complete cytoreduction. After a median follow-up of 30 months (range 9-95 months), median PFS was 32 months (CI 17-76 months) and median OS has not reached. Seventeen patients have died and 32 have progressed. Three patients had Clavien-Dindo grade-3 and two had grade-4 morbidity. Patients who had multi-site recurrence had shorter median PFS (p = 0.04) and patients who required bowel resections had blower median OS (p = 0.009) compared to rest of the cohort.IMPACT STATEMENT What is already known on this subject? Retrospective studies have confirmed survival advantage for recurrence in epithelial ovarian cancer and recommend SCS for carefully selected patients. This finding is being evaluated in randomised control trials currently.What do the results of this study add? This study presents excellent results for survival outcomes after SCS and highlights importance of careful selection of patients with a goal to achieve complete cytoreduction. In addition, for the first time in literature, this study also explores various factors that may influence results and finds that there are no differences in survival outcomes whether these patients had early stage or advanced stage disease earlier. Patients who have multisite recurrence tend to have shorter PFS but no difference were noted for overall survival. Patients who have recurrence in bowels necessitating resection/s have a shorter median OS compared to rest of cohorts, however, still achieving a good survival time. What are the implications of these findings for clinical practice and/or further research? These findings will raise awareness for the clinicians and patients while discussing surgical outcomes and would set an achievable standard to improve cancer services. The pattern of recurrence and associated outcomes also point towards difference in biological nature of recurrent disease and could provide an opportunity for scientists to study the biological makeup of these recurrent tumours.
  • Ultrasound guidance in reproductive surgery.

    Jayaprakasan, Kanna (2019-08)
    Ultrasound plays a key role in diagnosis and guidance in reproductive medicine and surgery. In the field of reproductive surgery, some of the interventions, especially intrauterine procedures, are regularly conducted without imaging guidance but instead performed based on clinical skills and experience alone. Operative real-time US provides concurrent visualisation of the structures, contents and planes and operating instruments and, therefore, has the potential to improve efficacy and safety of the operative interventions. Ultrasound should be used in our operating theatres more often to guide various intrauterine procedures to reduce the intra-operative risks and complications including uterine perforations and visceral injury. The use of ultrasound necessitates an additional assistant experienced in ultrasound in the theatre, but regular use of ultrasound improves the training opportunities of the trainees and clinicians.
  • The strength of evidence supporting luteal phase progestogen after assisted reproduction: A systematic review with reference to trial registration and pre-specified endpoints.

    Jayaprakasan, Kanna (2019-12)
    OBJECTIVE: To measure the potential for outcome switching and selective reporting, in trials of luteal phase progestogen in assisted reproduction. STUDY DESIGN: Trials identified through Medline and Embase in August 2017 using the MeSH term "assisted reproductive technology, luteal phase support" and associated text words. Randomised controlled trials (RCTs) comparing progestogen of any type, dose, and route of administration, with placebo or no treatment as luteal phase support in subfertile women undergoing in vitro fertilization (IVF) or intrauterine insemination (IUI). Eight trials after IVF and eleven after IUI, involving 1040 and 2764 participants respectively, were included. RESULTS: None of the eight trials of progestogen therapy after IVF had been registered. Only 5/11 trials of progestogen after IUI had been registered, and only two of these prospectively. One of these had a registered primary outcome of "pregnancy sac plus heartbeat", but reported "pregnancy sac alone"; we judged this as an altered primary outcome. Three other trial had a registered primary outcome of "clinical pregnancy undefined" and reported "intra or extra-uterine pregnancy with a heartbeat"; we judged this alteration as minimal. That trial was negative. Overall, 26 different outcomes had been reported by the various trials. The three outcomes reported most often were pregnancy undefined (9/19), miscarriage (11/19) and clinical pregnancy (9/19). This suggests considerable potential for selective outcome reporting or outcome switching. CONCLUSION: Apart from one negative trial, none of the evidence on luteal phase progestogen after assisted reproduction comes from prospectively registered trials: a slender reed indeed.
  • Socioeconomic differences impact overall survival in advanced ovarian cancer (AOC) prior to achievement of standard therapy.

    Phillips, A (2019-08)
    PURPOSE: Survival difference between socioeconomic groups with ovarian cancer has persisted in the United Kingdom despite efforts to reduce disparities in care. Our aim was to delineate critical episodes in the patient journey, where deprivation has most impact on survival. METHODS: A retrospective review of 834 patients with advanced ovarian cancer (AOC) between 16/8/07-16/2/17 at a large cancer centre serving one of the most deprived areas of the UK. Using the Index of Multiple Deprivation (IMD), patients were categorised into five groups. RESULTS: Surgery was more common in less deprived patients (p < 0.00001). Across IMD groups, there were no differences in complete (R0) cytoreduction rate (r = 0.18, p > 0.05), age, or comorbidity. The R0/total cohort rate increased with increasing IMD group (p < 0.0001). Patients refusing any intervention belonged exclusively to the three most deprived groups; 5/7 patients who refused surgery belonged to the most deprived IMD group. Overall survival in the total patient group was less in IMD group 1-2 compared to 9-10 (p = 0.002). On multivariate analysis, IMD group was not an independent predictor of survival (p > 0.05). CONCLUSIONS: Socioeconomic differences in survival manifest in patients not receiving surgical treatment for AOC and are not purely explained by comorbidity, age, stage, or histological factors.
  • Practical Guidance for Measuring and Reporting Surgical Margins in Vulvar Cancer

    Van Schalkwyk, Gerhard (2019-08)
    Surgical resection with free surgical margins is the cornerstone of successful primary treatment of vulvar squamous cell carcinoma (VSCC). In general reexcision is recommended when the minimum peripheral surgical margin (MPSM) is <8 mm microscopically. Pathologists are, therefore, required to report the minimum distance from the tumor to the surgical margin. Currently, there are no guidelines on how to make this measurement, as this is often considered straightforward. However, during the 2018 Annual Meeting of the British Association of Gynaecological Pathologists (BAGP), a discussion on this topic revealed a variety of opinions with regard to reporting and method of measuring margin clearance in VSCC specimens. Given the need for uniformity and the lack of guidance in the literature, we initiated an online survey in order to deliver a consensus-based definition of peripheral surgical margins in VSCC resections. The survey included questions and representative diagrams of peripheral margin measurements. In total, 57 pathologists participated in this survey. On the basis of consensus results, we propose to define MPSM in VSCC as the minimum distance from the peripheral edge of the invasive tumor nests toward the inked peripheral surgical margin reported in millimeters. This MPSM measurement should run through tissue and preferably be measured in a straight line. Along with MPSM, other relevant measurements such as depth of invasion or tumor thickness and distance to deep margins should be reported. This manuscript provides guidance to the practicing pathologist in measuring MPSM in VSCC resection specimens, in order to promote uniformity in measuring and reporting.

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