• Eag and HERG potassium channels as novel therapeutic targets in cancer.

      Asher, Viren; Bali, Anish (2010-12)
      Voltage gated potassium channels have been extensively studied in relation to cancer. In this review, we will focus on the role of two potassium channels, Ether à-go-go (Eag), Human ether à-go-go related gene (HERG), in cancer and their potential therapeutic utility in the treatment of cancer. Eag and HERG are expressed in cancers of various organs and have been implicated in cell cycle progression and proliferation of cancer cells. Inhibition of these channels has been shown to reduce proliferation both in vitro and vivo studies identifying potassium channel modulators as putative inhibitors of tumour progression. Eag channels in view of their restricted expression in normal tissue may emerge as novel tumour biomarkers.
    • Synovial sarcoma of the vulva: a case report.

      Asher, Viren; Van Schalkwyk, Gerhard; Bali, Anish (2011-03)
      INTRODUCTION: Contrary to its name, synovial sarcoma does not arise from the synovial membrane but from multipotent stem cells and can present in any part of the body. Very few cases of vulval synovial sarcoma have been reported in the literature; we report on such a presentation. These tumors can present as painless lumps, which must be completely excised to give the best prognosis. Therefore the diagnosis of synovial sarcoma should always be kept in mind in the management of vulval masses, especially in young patients. CASE PRESENTATION: We report the case of a 28-year-old Caucasian woman with synovial sarcoma of the vulva. Complete excision was possible in this case. CONCLUSION: We have presented a rare case of synovial sarcoma of the vulva, which can be easily confused with lipoma of the vulva. The management of this tumor requires referral to a cancer centre, with a multidisciplinary approach.
    • Obstetric and neonatal outcomes for women with reversed and non-reversed type III female genital mutilation.

      Raouf, Sanaria (2011-05)
      OBJECTIVE: To record and compare obstetric and neonatal complication rates in women with reversed and non-reversed type III female genital mutilation (FGM). METHODS: A retrospective observational study comparing cesarean delivery rates and neonatal outcomes of primiparous and multiparous women who had or had not undergone reversal of FGM III. RESULTS: Of the 250 women, 230 (92%) had an FGM reversal. Of these, 50 (21.7%) were primiparous (cesarean delivery rate 17/50; 34%) and 180 (78.3%) were multiparous (cesarean delivery rate 28/180; 15.6%). Of the 20 women who had not had an FGM reversal, 7 (35%) were primiparous (cesarean delivery rate 5/7; 71.4%) and 13 (65%) were multiparous (cesarean delivery rate 7/13; 53.8%). The cesarean delivery rates for primiparae and multiparae were 32.9% and 25%, respectively. Multiparous women with FGM III reversal had a lower possibility of caesarean delivery compared with the hospital multiparous population (P=0.003) and multiparae who had not undergone FGM III reversal (P=0.007). There was no significant association between Apgar scores or blood loss at vaginal delivery and FGM reversal. CONCLUSION: Reversal of FGM III significantly reduced the increased risk of cesarean delivery seen with multiparae who have FGM III.
    • Preoperative serum albumin is an independent prognostic predictor of survival in ovarian cancer.

      Asher, Viren; Lee, Joanne; Bali, Anish (2011-07)
      Ovarian cancer is associated with high mortality due to asymptomatic nature of the disease and advance stage at presentation. In advanced stages, it is associated with cachexia and ascites leading to malnutrition. Nutritional status of a patient with cancer has been well known to be associated with survival and can be assessed by level of albumin in blood. Therefore, in this study, we sought to determine preoperative serum albumin as prognostic predictor of survival in patients with ovarian cancer. Preoperative serum albumin was determined in 235 patients undergoing surgery for ovarian cancer at Royal Derby Hospital. The prognostic predictive value of serum albumin, along with other prognostic markers was then analysed using univariate and multivariate analyses. Low serum albumin was associated with poor survival (P 35 g/l were associated with median survival of 43.2 months (95% CI 11.6-20.9). Serum albumin (P < 0.001) retained its significance as an independent predictor of poor survival on Cox's multivariate regression analysis along with Age (P < 0.001) and FIGO stage (P < 0.001). Serum albumin can be used as an independent prognostic predictor of survival in patients with ovarian cancer.
    • The relationship of ethnicity, maternal height and shoe size, and method of delivery.

      Okewole, I; Amer, Saad (2011-10)
      In a bid to determine the relationship of ethnicity, maternal height and shoe size as predictors of cephalopelvic disproportion, we conducted a prospective comparative study of primigravidas at term with singleton pregnancies, who had undergone spontaneous labour. A total of 208 primigravidas were studied; 151 (62.9%) achieved vaginal delivery and 57 (37.1%) had emergency caesarean section for failure-to-progress. We found a statistically significant positive correlation between maternal height and vaginal delivery (p = 0.04), but no correlation with maternal shoe size was found (p = 0.24). This study also showed that Caucasian women were significantly more than twice as likely to achieve vaginal delivery compared with Africans (p = 0.02). Maternal height of at least 162.5 cm, has a sensitivity of 74% and a specificity of 43% for predicting vaginal delivery. We concluded that the most predictive anthropometric measurement for vaginal delivery is maternal height.
    • Pelvic mass associated with raised CA 125 for benign condition: a case report.

      Asher, Viren (2012-04)
      BACKGROUND: Raised CA 125 with associated pelvic mass is highly suggestive of ovarian malignancy, but there are various other benign conditions that can be associated with pelvic mass and a raised CA 125. CASE PRESENTATION: We present a case of 19 year old, Caucasian British woman who presented initially with sudden onset right sided iliac fossa pain and on imaging was found to have 9.8 x 4.5 cm complex cystic mass in right adnexa with a raised CA 125 of 657, which was initially thought to be highly suspicious of cancer but was subsequently found to be due to pelvic inflammatory disease on histology. CONCLUSION: This case highlights the fact that though a pelvic mass with raised CA 125 is highly suggestive of malignancy, pelvic inflammatory disease should always be considered as a differential diagnosis especially in a young patient and a thorough sexual history and screening for pelvic infection should always be carried out in these patients.
    • A case of caesarean scar ectopic pregnancy-successful treatment with intra-amniotic methotrexate followed by a systemic course of intramuscular methotrexate

      Robertson, C; Pettipiece, L; Tamizian, Onnig; Allsop, J (2013-12)
      Case: A 34-year-old woman, G5 P2 was seen at the Royal Derby Hospital in early pregnancy. Previous deliveries were by emergency caesarean section, the first at 30 weeks of gestation for a ruptured uterus and the second at 34 weeks for placenta praevia. Ultrasound scan showed a live pregnancy of 6+1 weeks with the gestation sac deeply embedded in the caesarean section scar. Myometrium could not be seen on the outer surface of the uterus and the pregnancy was closely applied to the bladder wall. A complete pregnancy percreta through the old scar was diagnosed. Although asymptomatic, the patient was offered termination of the pregnancy and a review of the literature was undertaken to decide how to safely manage the case. The patient initially underwent uterine artery methotrexate infusion via femoral catheters and embolization, however this was unsuccessful and a fetal heart was still present 7 days following treatment. After further counselling, the patient underwent intra-amniotic methotrexate and intra-cardiac lignocaine into the pregnancy, followed by alternate day intra-muscular methotrexate over 1 week, with alternate day folic acid. The treatment was successful and the patient went home 8 days after the initial treatment with falling beta-hCG levels. Discussion: The diagnosis of a complete pregnancy percreta through an old scar highlighted considerable risks for this patient. These included severe retro-vesical bleeding that would most likely require surgical resolution with the loss of the uterus and possible bladder damage. A number of problems may have been encountered if the pregnancy had continued, for example, severe placental insufficiency due to abnormal vascular supply, very pre-term delivery or intra-uterine demise. There was the risk of retro- or intra-vesical severe haemorrhage, and the likelihood of caesarean hysterectomy with bladder involvement as well as the risk of maternal loss of life due to uncontrollable haemorrhage, particularly after 20 weeks of gestation.
    • An audit of outpatient hysteroscopy in Royal Derby Hospital

      Kolhe, Shilpa; Shittu, SA; Petipiece, L (2014-04)
      Introduction Hysteroscopy offers an extension of the gynaecologists' armamentarium as it improves the diagnostic accuracy and permits better treatment of abnormal intra-uterine conditions. All gynaecological units should provide dedicated outpatient hysteroscopy service as it is associated with clinical and economic benefits. The objective was to assess the compliance of our practice with the standards in the RCOG/BSGE guideline and to assess correlation between our hysteroscopic and histological findings. The auditable standards of the RCOG that were assessed include success rate and reasons for failures, rate of cervical dilatation, and percentage of women with written information leaflet and informed consent. Methods We retrospectively reviewed the medical notes of 114 patients who had hysteroscopy over 3 months period in Royal Derby Hospital. Data obtained were analysed using Microsoft excel software. Result The result showed that postmenopausal bleeding (48%) was the commonest indication for the referral to the outpatient clinic. Success rate was 90.4%. All the patients were given information leaflets prior to consent. Recommended vaginoscopy approach was used in 63.2%, cervical dilation was done in 15%. Success rate of outpatient polypectomy was 84.4%. Documentation was considered standard in 84.2% of patients. The correlation between histology and hysteroscopic findings was satisfactory with sensitivity of 100% and specificity of 75% for endometrial carcinoma. Hysteroscopy could not differentiate between endometrial hyperplasia and carcinoma. Where no sample was available for histology, hysteroscopy was significantly helpful. Conclusion We recommended expansion of the outpatient operative service to include endometrial ablation, sterilisation and removal of submucous fibroids and use of a standardised proforma for documentation of procedure in all patients. The audit revealed good compliance with guideline and that outpatient hysteroscopy service in the hospital was efficient. Hysteroscopy is invaluable where sample is not available for histology.
    • Prospective study of one-stop diagnostic and see-and-treat outpatient hysteroscopy service at Royal Derby Hospital

      Kolhe, Shilpa (2014-04)
      Introduction Abnormal uterine bleeding is the most common problem that a woman is referred with to a gynaecology clinic. This study evaluates the important role of a one-stop diagnostic, see-and-treat outpatient hysteroscopy service set up in an ambulatory gynaecology unit at Royal Derby Hospital. Methods This is a prospective study of 762 consecutive patients attending ambulatory hysteroscopy clinics. Ambulatory clinic included outpatient hysteroscopy (OPH) clinic, one-stop postmenopausal bleeding clinic and polyp treatment clinic. Results 323/762 (42.3%) patients were referred with postmenopausal bleeding (to one-stop PMB clinic); 148 (19.4%) with ultrasound diagnosis of endometrial polyp (to polyp treatment clinic); 262 (34%) with other menstrual disorders and other indications to other OPH clinics. Outpatient hysteroscopywas performedsuccessfully in 694 cases (success rate of 91%). In further 39 cases, OPH was attempted but abandoned due to cervical stenosis (n = 17), poor views (n = 10), severe vasovagal attack (n = 2) or patient discomfort (n = 10). OPH was performed using vaginoscopic approach in 60% cases. Among those with recorded BMI, 60 women attending OPH clinics had BMI over 40. 223 endometrial polyps and 37 cervical polyps were removed successfully in one-stop setting. Endometrial polyps were treated using either bipolar electrosurgical versapoint electrode (58%), mechanical hysteroscopic devices such as polyp snare or grasping forceps under direct vision (15.5%) or more recently miniature hysteroscopictruclearmorcellator (26.5%) enabling diagnosis and treatment of this common lesion in the same setting. Hysteroscopic retrieval of IUCD with lost threads was done in 100% cases (n = 22). Local anaesthetic was only required in 12% cases. In a patient satisfaction survey conducted in a random sample of 100 women, 94% said they were very satisfied or fairly satisfied with their OPH procedure and 89% reported pain scores of <2.9 on a visual analog scale (VAS) of 1-5. 59.7% (n = 455) seen in this one-stop clinic were reassured and discharged from the clinic with subsequent written notification of histology result; 31% (n = 234) had follow-up arranged for histology review either in oncology clinic if anticipated abnormal result or in general gynaecology clinic for any other reason to follow-up; 9.3% (n = 71) were added to waiting list for general anaesthetic procedure. Conclusion OPH is a safe, minimally invasive surgical procedure not only for diagnosis in women with abnormal uterine bleeding, but is also a feasible, cost-effective and patient-friendly way of treating the causes of abnormal bleeding in majority of cases in the same sitting.
    • Female adipocyte androgen synthesis and the effects of insulin

      Amer, Saad (2014-06)
      The metabolic syndrome is a cluster of metabolic disorders characterized by insulin resistance and hyperinsulinaemia, and its presence can increase the risk of cardiovascular disease significantly. The metabolic syndrome is associated with increased circulating androgen levels in women, which may originate from the ovaries and adrenal glands. Adipocytes are also able to synthesise steroid hormones, and this output has been hypothesised to increase with elevated insulin plasma concentrations. However, the contribution of the adipocytes to the circulating androgen levels in women with metabolic syndrome is limited and the effects of insulin are not fully understood. The aim of this study was to investigate the presence of steroid precursors and synthetic enzymes in human adipocyte biopsies as markers of possible adipocyte androgen synthesis. We examined pre and mature adipocytes taken from tissue biopsies of abdominal subcutaneous adipose tissue of participating women from the Department of Obstetrics and Gynaecology, of the Royal Derby Hospital. The results showed the potential for localised adipocyte androgen synthesis through the presence of the androgen precursor progesterone, as well as the steroid-converting enzyme 17α-hydroxylase. Furthermore, we found the controlled secretion of androstenedione in vitro and that insulin treatment caused levels to increase. Continued examination of a localised source of androgen production is therefore of clinical relevance due to its influence on adipocyte metabolism, its negative impact on female steroidogenic homeostasis, and the possible aggravation this may have when associated to obesity and obesity related metabolic abnormalities such as hyperinsulinaemia.
    • Enigma of urethral pain syndrome: why are there so many ascribed etiologies and therapeutic approaches?

      Chilaka, Victor; Okewole, I; Phillip, H (2014-06)
      Urethral pain syndrome has had several sobriquets, which have led to much confusion over the existence of this pathological condition and the useful options in the care of the afflicted patient. Our aim was to explore the proposed etiologies of this syndrome, and to provide a critical analysis of each proposed etiology and present a balanced argument on the plausibility of the proposed etiology and therapeutic approaches. We carried out an English language electronic search in the following databases: Medline, Embase, Amed, Cinahl, Pubmed, Cochrane Library, Trip Database and SUMSearch using the following search terms: urethral syndrome, urethral diseases, urethra, urologic diseases etiology/etiology, presentation, treatment, outcome, therapeutics and treatment from 1951 to 2011. In excess of 200 articles were recovered. With the clearly defined objectives of analyzing the proposed etiologies and therapeutic regimes, two author(s) (HP and IO) perused the abstracts of all the recovered articles, selecting those that addressed the etiologies and therapeutic approaches to treating the urethral pain syndrome. The number of articles was reduced to 25. The full text of all 25 articles were retrieved and reviewed. Through the present article, we hope to elucidate the most probable etiology of this condition whilst simultaneously, advance a logical explanation for the apparent success in the treatment of this condition using a range of different therapeutic modalities. We have carried out a narrative review, which we hope will reduce some of the confusion around this clinical entity by combining the known facts about the disease.
    • Heparin for assisted reproduction: summary of a Cochrane review.

      Jayaprakasan, Kanna (2015-01)
      It is suggested that heparin given in the peri-implantation period may improve clinical outcomes in women undergoing assisted reproduction techniques (ART). This systematic review evaluates the use of heparin in subfertile women undergoing ART.
    • "I'm 100% for it! I'm a convert!": women's experiences of a yoga programme during treatment for gynaecological cancer; an interpretative phenomenological analysis.

      Bali, Anish (2015-02)
      To explore patients' experiences of taking part in a yoga intervention while undergoing treatment for gynaecological cancer. Sixteen women (age range 31-79 years; mean age 60) participated in focus groups based on a semi-structured question schedule. Resulting discussions were audio-recorded, transcribed verbatim and analysed using interpretative phenomenological analysis (IPA). Royal Derby Hospital, UK. Patients took part in a 10-week course of Hatha yoga, where they participated in a one hour long class per week. Three themes emerged from the data: applying breathing techniques, engaging in the physicality of yoga and finding a community. The first theme was particularly important to the patients as they noted the breadth and applicability of the techniques in their day-to-day lives. The latter two themes reflect physical and social perspectives, which are established topics in the cancer and yoga literature and are contextualised here within the women's experiences of cancer treatment. The women's perceptions of the programme were generally positive, providing a previously unseen view of the patient experience of participating in a yoga intervention. The difference between the women's prior expectations and lived experiences is discussed.
    • Acute herpes simplex encephalitis in pregnancy.

      Dobson, Samuel; Muppala, H (2015-03)
    • Risk Algorithm Using Serial Biomarker Measurements Doubles the Number of Screen-Detected Cancers Compared With a Single-Threshold Rule in the United Kingdom Collaborative Trial of Ovarian Cancer Screening.

      Jenkins, Howard; Scott, Ian (2015-06)
      PURPOSE: Cancer screening strategies have commonly adopted single-biomarker thresholds to identify abnormality. We investigated the impact of serial biomarker change interpreted through a risk algorithm on cancer detection rates. PATIENTS AND METHODS: In the United Kingdom Collaborative Trial of Ovarian Cancer Screening, 46,237 women, age 50 years or older underwent incidence screening by using the multimodal strategy (MMS) in which annual serum cancer antigen 125 (CA-125) was interpreted with the risk of ovarian cancer algorithm (ROCA). Women were triaged by the ROCA: normal risk, returned to annual screening; intermediate risk, repeat CA-125; and elevated risk, repeat CA-125 and transvaginal ultrasound. Women with persistently increased risk were clinically evaluated. All participants were followed through national cancer and/or death registries. Performance characteristics of a single-threshold rule and the ROCA were compared by using receiver operating characteristic curves. RESULTS: After 296,911 women-years of annual incidence screening, 640 women underwent surgery. Of those, 133 had primary invasive epithelial ovarian or tubal cancers (iEOCs). In all, 22 interval iEOCs occurred within 1 year of screening, of which one was detected by ROCA but was managed conservatively after clinical assessment. The sensitivity and specificity of MMS for detection of iEOCs were 85.8% (95% CI, 79.3% to 90.9%) and 99.8% (95% CI, 99.8% to 99.8%), respectively, with 4.8 surgeries per iEOC. ROCA alone detected 87.1% (135 of 155) of the iEOCs. Using fixed CA-125 cutoffs at the last annual screen of more than 35, more than 30, and more than 22 U/mL would have identified 41.3% (64 of 155), 48.4% (75 of 155), and 66.5% (103 of 155), respectively. The area under the curve for ROCA (0.915) was significantly (P = .0027) higher than that for a single-threshold rule (0.869). CONCLUSION: Screening by using ROCA doubled the number of screen-detected iEOCs compared with a fixed cutoff. In the context of cancer screening, reliance on predefined single-threshold rules may result in biomarkers of value being discarded.
    • Setting up of ambulatory hysteroscopy service.

      Kolhe, Shilpa (2015-10)
      There is an obvious trend towards developing ambulatory procedures in gynaecology with ambulatory hysteroscopy as its mainstay. In the recent years, the fast pace of modern technological advances in gynaecologic endoscopy, and particularly in the field of hysteroscopy, have been both thrilling and spectacular. Despite this, the uptake of operative hysteroscopy in ambulatory settings has been relatively slow. There is some apprehension amongst gynaecologists to embark on therapeutic outpatient hysteroscopy, and an organisational change is required to alter the mindset. Although there are best practice guidelines for outpatient hysteroscopy, there are unresolved issues around adequate training and accreditation of future hysteroscopists. Virtual-reality simulation training for operative hysteroscopy has shown promising preliminary results, and it is being aggressively evaluated and validated. This review article is an attempt to provide a useful practical guide to all those who wish to implement ambulatory hysteroscopy services in their outpatient departments.
    • To assess whether anti-mullerian hormone varies between women of different race/ethnic backgrounds

      Nayini, Krishnaveni; Korrapati, Siva; Jayaprakasan, Kanna (2016)
      Introduction: Anti-Mullerian hormone, secreted by the granulosa cells in the ovary, is used as an estimate of ovarian reserve and to predict the ovarian response to ovarian stimulation during assisted conception treatments. Differences in serum AMH levels amongst various ethnic groups have been reported in the literature. The results from literature have been conflicting and not uniform as regards the population and ethnic groups studied. Ovarian reserve remains an important predictor of the success of fertility treatments, ethnic differences in AMH may contribute to the differences in outcome of these treatments. Methods: Observational cross-sectional study of 1215 patients who had levels measured between April 2009 to September 2014 at Royal Derby Hospital over a period of 5 years. Serum Anti-Mullerian hormone levels were compared amongst women from three different ethnic groups. Results: A total of 1215 women studied, 874 were Caucasians, 178 were Asians, 23 were Afro Caribbean's, 4 from mixed back ground and 128 of them have not stated their ethnicity. The data shows that Caucasians had high levels of Anti-Mullerian hormone compared to Asian and African women at younger age (up to 30 yrs). Caucasian women showed highest decline in Anti-Mullerian hormone levels compared to Asian and African women between 30-44yrs. African women had lowest Anti-Mullerian hormone levels throughout their reproductive period compared to Caucasians and Asians. Discussion / Conclusion: As age advances AMH levels decrease, the degree of age related AMH decline vary depending on ethnicity, cause of subfertility and type of subfertility. Ethnicity should be considered while interpreting AMH results. Improving our understanding of racial differences in ovarian reserve and their underlying causes may be essential for reproductive planning, improved treatment outcomes.
    • Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial.

      Jenkins, Howard (2016-03)
      BACKGROUND: Ovarian cancer has a poor prognosis, with just 40% of patients surviving 5 years. We designed this trial to establish the effect of early detection by screening on ovarian cancer mortality. METHODS: In this randomised controlled trial, we recruited postmenopausal women aged 50-74 years from 13 centres in National Health Service Trusts in England, Wales, and Northern Ireland. Exclusion criteria were previous bilateral oophorectomy or ovarian malignancy, increased risk of familial ovarian cancer, and active non-ovarian malignancy. The trial management system confirmed eligibility and randomly allocated participants in blocks of 32 using computer-generated random numbers to annual multimodal screening (MMS) with serum CA125 interpreted with use of the risk of ovarian cancer algorithm, annual transvaginal ultrasound screening (USS), or no screening, in a 1:1:2 ratio. The primary outcome was death due to ovarian cancer by Dec 31, 2014, comparing MMS and USS separately with no screening, ascertained by an outcomes committee masked to randomisation group. All analyses were by modified intention to screen, excluding the small number of women we discovered after randomisation to have a bilateral oophorectomy, have ovarian cancer, or had exited the registry before recruitment. Investigators and participants were aware of screening type. This trial is registered with ClinicalTrials.gov, number NCT00058032. FINDINGS: Between June 1, 2001, and Oct 21, 2005, we randomly allocated 202,638 women: 50,640 (25·0%) to MMS, 50,639 (25·0%) to USS, and 101,359 (50·0%) to no screening. 202,546 (>99·9%) women were eligible for analysis: 50,624 (>99·9%) women in the MMS group, 50,623 (>99·9%) in the USS group, and 101,299 (>99·9%) in the no screening group. Screening ended on Dec 31, 2011, and included 345,570 MMS and 327,775 USS annual screening episodes. At a median follow-up of 11·1 years (IQR 10·0-12·0), we diagnosed ovarian cancer in 1282 (0·6%) women: 338 (0·7%) in the MMS group, 314 (0·6%) in the USS group, and 630 (0·6%) in the no screening group. Of these women, 148 (0·29%) women in the MMS group, 154 (0·30%) in the USS group, and 347 (0·34%) in the no screening group had died of ovarian cancer. The primary analysis using a Cox proportional hazards model gave a mortality reduction over years 0-14 of 15% (95% CI -3 to 30; p=0·10) with MMS and 11% (-7 to 27; p=0·21) with USS. The Royston-Parmar flexible parametric model showed that in the MMS group, this mortality effect was made up of 8% (-20 to 31) in years 0-7 and 23% (1-46) in years 7-14, and in the USS group, of 2% (-27 to 26) in years 0-7 and 21% (-2 to 42) in years 7-14. A prespecified analysis of death from ovarian cancer of MMS versus no screening with exclusion of prevalent cases showed significantly different death rates (p=0·021), with an overall average mortality reduction of 20% (-2 to 40) and a reduction of 8% (-27 to 43) in years 0-7 and 28% (-3 to 49) in years 7-14 in favour of MMS.INTERPRETATION: Although the mortality reduction was not significant in the primary analysis, we noted a significant mortality reduction with MMS when prevalent cases were excluded. We noted encouraging evidence of a mortality reduction in years 7-14, but further follow-up is needed before firm conclusions can be reached on the efficacy and cost-effectiveness of ovarian cancer screening. FUNDING: Medical Research Council, Cancer Research UK, Department of Health, The Eve Appeal.
    • Patent foramen ovale as a cause of platypnea orthodeoxia syndrome presenting in pregnancy: A case report and review of the literature

      Dewick, Laura; Ashworth, J (2016-06)
      Background At 8 weeks into her third IVF pregnancy, a 40-yearold doctor presented to the Royal Derby Hospital with dyspnoea. Her breathing had worsened since the drainage of 5 litres of ascites from ovarian hyperstimulation syndrome 3 weeks prior. Her symptoms deteriorated and she was intermittently hospitalised from 28 weeks, as she was unable to sit upright without desaturating to 75% in air. This presentation was consistent with Platypnea-Orthodeoxia Syndrome (shortness of breath and arterial desaturation when upright which improves when supine). Investigations including chest X-ray, VQ scan, CTPA, Spirometry, Echo and ECG were normal. Bubble echo was initially normal, but when repeated 2 weeks later it demonstrated a right to left shunt consistent with a patent foramen ovale (PFO). She underwent a caesarean section at 35 weeks following which her symptoms resolved entirely. Objectives To establish the incidence of PFO in women of reproductive age, presenting symptoms, diagnostic tests and options for management. Methods Review of recent literature via a web based search. Results Patent Foramen Ovale is known to affect up to 1 in 3 adults based on autopsy findings from around 1000 'normal' hearts. The incidence in those aged under 30 years is 34.3%, falling to 25.4% in the over 40s. Size is known to increase with age. PFO affects men and women equally, with no difference in size between genders. It has long been recognised as a cause of unexplained stroke, particularly in those under 55, where the incidence is thought to rise to 56%. The vast majority of adults are asymptomatic, although it is occasionally associated with clinical syndromes including decompression syndrome in scuba divers, migraine (particularly with aura) and rarely with Platypnea-orthodeoxia syndrome. The diagnosis is made via Echocardiography, with trans-oesophageal echo considered the gold standard. In the UK use of 'bubble echo' has improved detection, as saline contrast is injected into a peripheral vein during the valsalva manoeuvre, following which bubbles can be seen crossing the septum. Management options include secondary prevention of paradoxical embolic stroke with anticoagulation, and percutaneous transcatheter closure. This method has now been developed for use in the second trimester to allow closure with minimal fetal radiation exposure. Conclusion Patent foramen ovale is a relatively common phenomenon in women of childbearing age and should therefore feature in the differential diagnosis of worsening shortness of breath in pregnancy, especially if positional
    • The impact of excision of benign nonendometriotic ovarian cysts on ovarian reserve: a systematic review.

      Amer, Saad (2016-08)
      BACKGROUND: Benign nonendometriotic ovarian cysts are very common and often require surgical excision. However, there has been a growing concern over the possible damaging effect of this surgery on ovarian reserve. OBJECTIVE: The aim of this metaanalysis was to investigate the impact of excision of benign nonendometriotic ovarian cysts on ovarian reserve as determined by serum anti-Müllerian hormone level. DATA SOURCES: MEDLINE, Scopus, ScienceDirect, and Embase were searched electronically. STUDY DESIGN: All prospective and retrospective cohort studies as well as randomized trials that analyzed changes of serum anti-Müllerian hormone concentrations after excision of benign nonendometriotic cysts were eligible. Twenty-five studies were identified, of which 10 were included in this analysis. DATA EXTRACTION: Two reviewers performed the data extraction independently. RESULTS: A pooled analysis of 367 patients showed a statistically significant decline in serum anti-Müllerian hormone concentration after ovarian cystectomy (weighted mean difference, -1.14 ng/mL; 95% confidence interval, -1.36 to -0.92; I(2) = 43%). Subgroup analysis including studies with a 3-month follow-up, studies using Gen II anti-Müllerian hormone assay and studies using IOT anti-Müllerian hormone assay improved heterogeneity and still showed significant postoperative decline of circulating anti-Müllerian hormone (weighted mean difference, -1.44 [95% confidence interval, -1.71 to -1.1; I(2) = 0%], -0.88 [95% confidence interval, -1.71 to -0.04; I(2) = 0%], and -1.56 [95% confidence interval, -2.44 to -0.69; I(2) = 22%], respectively). Sensitivity analysis including studies with low risk of bias and excluding studies with possible confounding factors still showed a significant decline in circulating anti-Müllerian hormone. CONCLUSION: Excision of benign nonendometriotic ovarian cyst(s) seems to result in a marked reduction of circulating anti-Müllerian hormone. It remains to be established whether this reflects a real compromise to ovarian reserve.