Uterine leiomyomatosis in adolescents and young adults (AYAs) may represent a narrow phenotypic variant of FH tumour predisposition syndrome.

FH Tumour Predisposition Syndrome, also known as Hereditary Leiomyomatosis and renal cell cancer (HLRCC), or Reed Syndrome, is an autosomal dominant condition clinically characterized by multiple cutaneous leiomyomas, multiple early-onset uterine leiomyomas and early-onset renal cell cancer. Here we report a young female with FH Tumour Predisposition Syndrome with no clinical features except early-onset uterine leiomyomas. Whilst there is a significant history of uterine leiomyomas in her family, there is no history of cutaneous leiomyomas or renal cell cancer (RCC). Uterine leiomyomatosis in young adults may represent a narrow phenotypic variant of FH Tumour Predisposition Syndrome. It is important that young women who present with multiple leiomyomata or leiomyomata with atypical features are referred for molecular genetic testing.

Developing Core Outcome Sets (COS) and Core Outcome Measures Sets (COMS) in Cosmetic Gynecological Interventions: Protocol for a Development and Usability Study.

BACKGROUND: Studies evaluating cosmetic gynecological interventions have followed variable methodology and reported a diversity of outcomes. Such variations limit the comparability of studies and the value of research-based evidence. The development of core outcome sets (COS) and core outcome measures sets (COMS) would help address these issues, ensuring a minimum of outcomes important to all stakeholders, primarily women requesting or having experienced cosmetic gynecological interventions. OBJECTIVE: This protocol describes the methods used in developing a COS and COMS for cosmetic gynecological interventions. METHODS: An international steering group within CHORUS, including health care professionals, researchers, and women with experience in cosmetic gynecological interventions from 4 continents, will guide the development of COS and COMS. Potential outcome measures and outcomes will be identified through comprehensive literature reviews. These potential COS and COMS will be entered into an international, multi-perspective web-based Delphi survey where Delphi participants judge which domains will be core. A priori thresholds for consensus will get established before each Delphi round. The Delphi survey results will be evaluated quantitatively and qualitatively in subsequent stakeholder group consensus meetings in the process of establishing "core" outcomes. RESULTS: Dissemination and implementation of the resulting COS and COMS within an international context will be promoted and reviewed. CONCLUSIONS: This protocol presents the steps in developing a COS and COMS for cosmetic gynecological interventions. Embedding the COS and COMS for cosmetic gynecological interventions within future clinical trials, systematic reviews, and practice guidelines could contribute to enhancing the value of research and improving overall patient care. TRIAL REGISTRATION: Core Outcome Measures in Effectiveness Trials (COMET) 1592; https://tinyurl.com/n8faysuh. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/28032.

Type II or type III radical hysterectomy compared to chemoradiotherapy as a primary intervention for stage IB2 cervical cancer.

BACKGROUND: Cervical cancer is the fourth most common cancer in women, with 528,000 estimated new cases globally in 2012. A large majority (around 85%) of the disease burden occurs in low- and middle-income countries (LMICs), where it accounts for almost 12% of all female cancers. Treatment of stage IB2 cervical cancers, which sit between early and advanced disease, is controversial. Some centres prefer to treat these cancers by radical hysterectomy, with chemoradiotherapy reserved for those at high risk of recurrence. In the UK, we treat stage IB2 cervical cancers mainly with chemoradiotherapy, based on the rationale that a high percentage will have risk factors necessitating chemoradiotherapy postsurgery. There has been no systematic review to determine the best possible evidence in managing these cancers. OBJECTIVES: To determine if primary surgery for stage IB2 cervical cancer (type II or type III radical hysterectomy with lymphadenectomy) improves survival compared to primary chemoradiotherapy.To determine if primary surgery combined with postoperative adjuvant chemoradiotherapy, for stage IB2 cervical cancer increases patient morbidity in the management of stage IB2 cervical cancer compared to primary chemoradiotherapy. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 3), MEDLINE via Ovid (1946 to April week 2, 2018) and Embase via Ovid (1980 to 2018 week 16). We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies up to April 2018. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs), quasi-RCTs or non-randomised studies (NRSs) comparing surgery to chemoradiotherapy in stage IB2 cervical cancers. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed whether potentially relevant studies met the inclusion criteria, abstracted data, assessed risk of bias and analysed data using standard methodological procedures expected by Cochrane. MAIN RESULTS: We identified 4968 records from the literature searches, but we did not identify any RCTs that compared primary surgery with chemoradiotherapy in stage IB2 cervical cancer.We found one NRS comparing surgery to chemoradiotherapy in IB2 and IIA2 cervical cancers which met the inclusion criteria. However, we were unable to obtain data for stage IB2 cancers only and considered the findings very uncertain due to a high risk of selection bias. AUTHORS' CONCLUSIONS: There is an absence of high-certainty evidence on the relative benefits and harms of primary radical hysterectomy versus primary chemoradiotherapy for stage IB2 cervical cancer. More research is needed on the different treatment options in stage IB2 cervical cancer, particularly with respect to survival, adverse effects, and quality of life to facilitate informed decision-making and individualised care.

Role of Systematic Lymphadenectomy to Tailor Adjuvant Therapy in Early Endometrial Cancer.

OBJECTIVE: The long-standing protocol at our center for apparent stage I and II endometrial cancers comprises hysterectomy and bilateral salpingo-oophorectomy without lymphadenectomy. Adjuvant treatment is based in line with Postoperative Radiation Therapy in Endometrial Carcinoma 1 protocol. Our aim was to quantify the number of patients who would avoid external beam radiation therapy (EBRT) in our institution if we adopted a protocol of lymphadenectomy to tailor adjuvant EBRT and its impact on cost and quality of life. DESIGN: Retrospective case-cohort study. SETTING: Gynecological oncology center. METHODS: All endometrial cancers treated from 2007 to 2012 were included. The European Organization for Research and Treatment of Cancer (EORTC) quality of life (QLQ-30) and endometrial cancer specific (EN-24) questionnaires were used to measure the quality of life. The NHS tariff for EBRT, VBT and lymphadenectomy were obtained from our Trust's contract with the local commissioning groups. MAIN OUTCOME MEASURES: Quality of life and cost. RESULTS: Systematic pelvic lymphadenectomy in early endometrial cancers of all grades would avoid EBRT in 23.3% of patients, and if performed for grade 2 and 3 cancers, 39.5% of patients would avoid EBRT. The global health scores were significantly lower, and pain scores were considerably higher in patients who received EBRT. Performing systematic lymphadenectomy and tailored adjuvant therapy in grade 2 and 3 endometrial cancers would save £134,691 and for all grades save £37,161 for every 100 patients treated with early endometrial cancer. CONCLUSION: Systematic lymphadenectomy with tailored adjuvant therapy may offer better QoL with reduced cost to NHS without a reduction in overall survival.

Paget's Disease of the Vulva: A Review of 20 Years' Experience.

BACKGROUND: Extramammary Paget's disease is a rare condition, and the vulva is a common site for it to occur. Despite this, there is a paucity of literature on Paget's disease of the vulva (VPD). A Cochrane meta-analysis could not draw any conclusions on interventions in VPD. Our aim was to review our practice and improve further management of VPD in our center. METHODS: We reviewed all the cases presented to Leeds Gynaecological Oncology Centre between 1988 and 2016. All cases identified in this interval were followed up until April 2016. All case notes and electronic patient data were retrieved to collate the data. RESULTS: We identified 18 cases of VPD. The median age at presentation was 76.9 years. Primary surgery was used in 18 cases. Eight patients had wide local excision with graft reconstruction. Ten women had wide local excision with primary reconstruction. Margins were negative in 27% of the excisions. Sixty percent of patients with clear surgical margins had a recurrence, and 69% of patients with positive margins had a recurrence; there was no statistical difference between the 2 groups for recurrence (P > 0.05). Fifty-eight percent of patients who had recurrence had coexisting malignancy. Logistic regression showed no correlation of recurrence rates due to either age, margin status, or coexisting malignancies. CONCLUSIONS: Paget's disease of the vulva is a rare condition. Our experience indicates that most cases may be amenable to surgical treatment at first presentation. Negative margin status does not reduce the chance of recurrence, and hence patients should be under follow-up for life. The benefit of radical surgery in the absence of reduced recurrences, based on margin status, is questionable. Radiotherapy and imiquimod are options for extensive lesions or recurrent settings. Coexisting malignancies are associated with VPD.

Traumatic Neuroma After Hysterectomy and Bilateral Salpingo-Oophorectomy: A Rare Cause of Post Hysterectomy Pelvic Pain.

The cause of posthysterectomy pain is frequently undiagnosed, and a presumed diagnosis of adhesions is made. Surgical division of adhesions often fails to alleviate the pain. As a result, posthysterectomy pain is seldom investigated despite being associated with a significant deterioration in the quality of life. We report a case of posthysterectomy bilateral neuroma of the autonomic nerves to the ovary that leads to significant pelvic pain. Excision of these neuromas resulted in complete resolution of pelvic pain and significant improvement in the quality of life. This interesting observation does not support the widespread use of laparoscopy for posthysterectomy pain but should be considered in patients with pain that occurs at an interval after hysterectomy who have had no pelvic pain preceding the hysterectomy.

Venous thromboembolism at time of diagnosis of ovarian cancer: Survival differs in symptomatic and asymptomatic cases.

OBJECTIVES: To determine the impact on survival of symptomatic and asymptomatic venous thromboembolism (VTE) at time of diagnosis of primary ovarian malignancy. MATERIALS AND METHODS: The clinical records of 397 consecutive cases of primary ovarian malignancy were studied. Clinical, pathological and survival data were obtained. RESULTS AND CONCLUSIONS: Of 397 cases, 19 (4.8%) were found to have VTE at diagnosis, of which 63.2% (n=12) were asymptomatic. VTE was significantly associated with reduced overall median survival (28 vs. 45 months, p=0.004). Decreased survival was associated with symptomatic VTE compared to patients with asymptomatic VTE (21 vs. 36 months, p=0.02) whose survival was similar to that of patients without VTE. Decreased survival remained significant in symptomatic patients after controlling for stage of disease at diagnosis, cytoreductive status and adjuvant chemotherapy use. Overall these data suggest for the first time that symptomatic but not asymptomatic VTE prior to primary treatment of ovarian cancer is an independent adverse prognostic factor.

Patient-reported outcome measures for follow-up after gynaecological cancer treatment.

BACKGROUND: Cancer is a leading cause of death worldwide. Gynaecologic cancer treatment is known to have the potential for a major impact on quality of life (QoL). Patient-reported outcome measures (PROMs) is an umbrella term that covers a range of potential types of measurement but is used specifically to refer to self reports by the patient of their health and well-being. Use of QoL and cancer-specific questionnaires as alternatives to follow-up may have immense psychological benefit to the patient and cost benefit to the healthcare system. OBJECTIVES: To evaluate the effectiveness of PROMs as an alternative to routine follow-up of women after treatment for gynaecological cancers to identify recurrences, affect overall survival and assess psychological benefit. SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Group Trials Register, MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) up to November 2012. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of review articles. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs) and non-RCTs with concurrent comparison groups (of adequate quality that used statistical adjustment for baseline case mix using multivariable analyses) that compared PROMs or QoL questionnaires versus traditional follow-up with multiple visits to the hospital in women after treatment for gynaecological cancers. Studies that involved women completing PROMs at intervals and submitting results for assessment by their cancer care team or structured interviews of women during their follow-up were included in the analysis. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed whether potentially relevant studies met the inclusion criteria. We found no studies and therefore analysed no data. MAIN RESULTS: The search strategy identified 2524 unique references, of which all were excluded. AUTHORS' CONCLUSIONS: We found no evidence to make an informed decision about PROMs for follow-up after gynaecological cancer. Ideally, RCTs which are multicentre or multinational or both, or well-designed non-randomised studies are needed that use multivariable analysis to adjust for baseline imbalances, to compare follow-up strategies and improve current knowledge.

Microvascular remodelling in preeclampsia: quantifying capillary rarefaction accurately and independently predicts preeclampsia.

BACKGROUND: Preeclampsia is a major cause of maternal and neonatal mortality and morbidity. The incidence of preeclampsia seems to be rising because of increased prevalence of predisposing disorders, such as essential hypertension, diabetes, and obesity, and there is increasing evidence to suggest widespread microcirculatory abnormalities before the onset of preeclampsia. We hypothesized that quantifying capillary rarefaction could be helpful in the clinical prediction of preeclampsia. METHODS: We measured skin capillary density according to a well-validated protocol at 5 consecutive predetermined visits in 322 consecutive white women, of whom 16 subjects developed preeclampsia. RESULTS: We found that structural capillary rarefaction at 20-24 weeks of gestation yielded a sensitivity of 0.87 with a specificity of 0.50 at the cutoff of 2 capillaries/field with the area under the curve of the receiver operating characteristic value of 0.70, whereas capillary rarefaction at 27-32 weeks of gestation yielded a sensitivity of 0.75 and a higher specificity of 0.77 at the cutoff of 8 capillaries/field with area under the curve of the receiver operating characteristic value of 0.82. Combining capillary rarefaction with uterine artery Doppler pulsatility index increased the sensitivity and specificity of the prediction. Multivariable analysis shows that the odds of preeclampsia are increased in women with previous history of preeclampsia or chronic hypertension and in those with increased uterine artery Doppler pulsatility index, but the most powerful and independent predictor of preeclampsia was capillary rarefaction at 27-32 weeks. CONCLUSIONS: Quantifying structural rarefaction of skin capillaries in pregnancy is a potentially useful clinical marker for the prediction of preeclampsia.

Structural capillary rarefaction and the onset of preeclampsia.

OBJECTIVE: To estimate if reduced capillary density (ie, capillary rarefaction) precedes the onset of preeclampsia and if it could play a role in its pathogenesis. Capillary rarefaction is a consistent finding in essential hypertension. METHODS: In this longitudinal cohort study, we recruited 322 consecutive white women, of whom 305 women completed the study. We used intravital video microscopy to measure basal (ie, functional) and maximal (ie, structural) skin capillary densities according to a well-validated protocol and measured plasma angiogenic and antiangiogenic factors. Women were studied at five consecutive predetermined visits. RESULTS: Preeclampsia occurred in 16 women (mean onset at 35.6±4.8 weeks of gestation), 272 women had normal pregnancies, eight had hypertension, and nine pregnancies were complicated by intrauterine growth restriction. In women with a normal pregnancy, significant reduction in maximal capillary density occurred at 27-32 weeks but had resolved by the puerperium. In contrast, in women who later developed preeclampsia, structural rarefaction was greater and occurred earlier at 20-24 weeks of gestation and persisted into the puerperium. We also found that the change in soluble Endoglin from 11-16 weeks of gestation to 27-32 weeks of gestation was significantly correlated with the change in structural capillary density. CONCLUSION: Significant structural capillary rarefaction precedes the onset of preeclampsia and could play a role in its pathogenesis. LEVEL OF EVIDENCE: II.

Capillary remodelling in normal pregnancy: Can it mediate the progressive but reversible rise in blood pressure? Novel insights into cardiovascular adaptation in pregnancy.

OBJECTIVE: To conduct a longitudinal study of skin capillary density changes throughout normal pregnancy and correlate them to changes in blood pressure. DESIGN: Prospective, longitudinal cohort study. SETTING: London teaching hospital. STUDY DESIGN: Two hundred and twenty-five Caucasian, Primigravid women with singleton pregnancy, normotensive throughout pregnancy, and with normal pregnancy outcomes. We used intra-vital video microscopy to measure basal (i.e. functional) and maximal (i.e. structural) skin capillary density (CD) according to a well-validated protocol. The subjects were studied at baseline (11-16weeks gestation) and at four consecutive visits (20-24weeks, 27-32weeks, 34-38weeks, and 5-15weeks postpartum). Blood pressure measurements were taken during the same visits. RESULTS: We found that normal pregnancy was associated with progressive capillary rarefaction, with the overall trend in the fall in both functional and structural CD being statistically significant (p<0.001). The fall in CD was a remarkable mirror image to a progressive rise in systolic and diastolic blood pressures, there being a significant correlation between systolic blood pressure and structural CD. Postpartum measurements of both CD and blood pressure were similar to base line levels. CONCLUSIONS: Progressive capillary rarefaction is a normal accompaniment of human pregnancy that may mediate the progressive rise in systolic and diastolic pressures. Both the CD and blood pressure changes are reversible, returning to baseline in the puerperium.

Mid-trimester blood pressure drop in normal pregnancy: myth or reality?

BACKGROUND: Current dogma states that there is a mid-trimester fall in blood pressure (BP) in uncomplicated pregnancy. In the early stages of a longitudinal study of microcirculatory changes in pregnancy, we noted an absence of this mid-trimester fall. METHOD: We prospectively studied this phenomenon in all our subsequent recruits. From a total of 326 women, 255 primigravid white women normotensive at booking and after delivery were studied. Serial BP measurements were taken under controlled conditions through to 38 weeks gestation. BP measurements by midwives were extracted from the case notes of 51 women within this cohort and analysed to validate the results. SBP progressively increased from the first trimester through to 38 weeks gestation. RESULTS: The increase from baseline at 13 weeks was significant when compared with measurements at 22 weeks [mean difference: 2.8 mmHg; 95% (confidence interval) CI 1.9-3.7], 28 weeks (mean difference: 5.0 mmHg; 95% CI 3.5-6.5) and 36 weeks (mean difference: 7.7 mmHg; 95% CI 6.2-9.1). DBP showed a nonsignificant dip at 22 weeks (mean difference: -0.12 mmHg; 95% CI -0.92 to 0.68), a nonsignificant increase at 28 weeks (mean difference: 2.0 mmHg; 95% CI 0.80-3.2) and a significant increase at 36 weeks (mean difference: 6.0; 95% CI 4.6-7.3). In the validation cohort, the SBP (P=0.0001) and DBP showed an increasing trend (P=0.0001). CONCLUSION: BP measured under controlled conditions showed a progressive rise in pregnancy, with no significant mid-trimester drop. The findings were replicated in the routine antenatal clinic measurements.

Tubal ectopic pregnancy: diagnosis and management.

Ectopic pregnancy is the gynaecological emergency par excellence and remains the leading cause of pregnancy-related first trimester deaths in the UK. Its prevalence continues to rise because of increases in the incidence of the risk factors predisposing to ectopic pregnancy. Classically, the diagnosis is based on a history of pelvic pain associated with amenorrhoea, a positive pregnancy test with or without slight vaginal bleeding. While the immediate differential diagnosis includes threatened or inevitable miscarriage, the likelihood of ectopic pregnancy is increased if transvaginal sonography (TVS) reveals an empty uterine cavity, and is confirmed if an adnexal mass with or without an embryo is seen. However, the diagnosis is often not that simple, especially when the patient presents early, has minimal pain, is haemodynamically stable, and TVS shows an empty uterus but no obvious adnexal mass. This could then be an early intrauterine pregnancy, or could indeed be an ectopic-a diagnosis of pregnancy of unknown location is made while additional investigations are made. The latter usually include serial measurements of serum beta human chorionic gonadotrophin (beta-hCG) and repeat TVS. Changes in beta-hCG levels in normal, failing and ectopic pregnancy are now reasonably well characterised, and at early stages of presentation where the risk of rupture of an ectopic are minimal, the patient can often be managed as an outpatient while the diagnosis is pursued. In the patient who presents with pain and haemodynamic instability, the diagnosis is often obvious, and the management is immediate laparotomy. However, in modern gynaecological practice in the developed world the vast majority of ectopic pregnancies present early, and the general consensus is that laparoscopic management offers both economic and aesthetic advantages, and should be used whenever possible. Salpingectomy (excision of the fallopian tube containing the ectopic) is performed if the contra-lateral tube is healthy, while salpingotomy (linear incision made in the fallopian tube with removal of ectopic pregnancy and conservation of tube) is performed if the contra-lateral tube is unhealthy. Medical therapy using methotrexate given systemically or injected directly into the ectopic pregnancy is an option occasionally used with good results. There appear to be no major differences in subsequent fertility outcomes, or risk of recurrence of ectopic pregnancy, between the surgical or medical treatments. Although the rates of ectopic pregnancy are not falling in the developed world, mortality and morbidity are falling mainly due to early and improving diagnostic and treatment modalities. Mass screening and treatment of Chlamydia in the young, sexually active populations, and education regarding risk factors, may in future result in a reduction in the rates. Lack of resource mean that the picture may remain dismal for some time to come in the developing world, but the development of basic protocols, improved training and the infusion of basic resources may go a long way to improving the situation.

Secondary abdominal appendicular ectopic pregnancy.

Although the case fatality rate for ectopic pregnancies has decreased to 0.08% in industrialized countries, it still represents 3.8% of maternal mortality in the United States alone. In developing countries, the case fatality rate varies from 3% to 27%. Laparoscopic management of tubal pregnancies is now the standard form of treatment where this technology is available. Abdominal pregnancies are rare, and secondary implantation of tubal ectopic pregnancies is the most common cause of abdominal gestations. We present an interesting case of secondary implantation of a tubal ectopic pregnancy to highlight the appendix as a possible secondary implantation site after a tubal ectopic pregnancy.

Umbilical cord rupture: a case report and review of literature.

The umbilical cord acts as a mechanical conduit between the fetus and placenta, allowing movement of water and nutrient substances between the fetal circulation and the amniotic fluid. Complications can occur antenatally or intranatally and are usually acute events that require immediate delivery to prevent intrauterine death. Even though the majority of the cord complications are unpreventable, significant improvement in perinatal mortality and morbidity can be achieved if such an event can be predicted. Umbilical cord rupture is not uncommon, but significantly underreported. We present an unusual cause of umbilical cord rupture and a review of literature.

The single unit transfusion in post partum hemorrhage: A new perspective.

Every year, about 210 million women become pregnant. Postpartum hemorrhage (PPH) is one of the major complications of pregnancy, accounting for 14 million cases annually. Of these, it is estimated that around 140,000 women die, resulting in a case fatality rate of 1%. PPH is defined by WHO as a blood loss > or = 500 mls. Most instances of PPH occur suddenly and without warning even in women without any of the known risks for this condition. If women do not receive timely medical treatment, as is often the case in many parts of the world, death can occur within two hours. The chance of receiving a safe blood transfusion as part of the therapy for PPH varies enormously from country to country, depending on whether a safe blood transfusion program has been set up as a part of the national health policy. The increasing realization of the potential deleterious effects of blood transfusion, including exposure to HIV and other viral agents, has changed the practices that were previously acceptable for the transfusion of blood, as has the recent recognition of specific patients who will benefit from a single unit of blood. In countries with limited resources, where a majority of women have anemia at the onset of their pregnancies, the slightest deviation from normality during labor and/or delivery leading to excessive hemorrhage can put a women's life at risk. In these instances, the patient needs urgent resuscitation, stabilization and transfer to a nearby center. Available blood, preferably typed cross matched and screened for infections, should be given until the patient receives specific treatment. This is especially true in bled- out obstetrics patients, where one unit may make the difference between a near death state and the possibility of slow recovery and survival.