Search

Introduction/Background Uncertainty remains regarding management of twin pregnancies comprising complete hydatidiform mole (CHM) and healthy co-twin. In 1998, we reported that continuing such pregnancies results in a 38% chance of a healthy baby, no maternal deaths or increased risk of malignancy requiring chemotherapy. However, other studies suggest a higher risk of malignancy and maternal mortality if such pregnancies are not terminated. Here, we re-examine this controversial issue in a new, larger national cohort. Methodology The UK hydatidiform mole databases were screened to identify all twin pregnancies with central pathology review confirming CHM and normal co-twin between 1998 and 2018. Data on rates of termination, spontaneous miscarriage, pregnancy complications, successful deliveries and need for chemotherapy were collected. Results 153 new patients had a confirmed CHM and healthy co-twin. Fifty electively terminated their pregnancy before 14 weeks. 103 continued beyond 14 weeks but 28 subsequently electively terminated, leaving 75 patients who continued their pregnancy. Their outcomes included: 11 terminations Conclusion Although malignancy risk is slightly greater following CHM and healthy co-twin than in singleton molar pregnancies, the risk does not increase with progression of pregnancy beyond the first trimester. Early termination is not necessary, and the likelihood of a healthy baby appears to be greater than previously reported. Disclosure MJS wishes to acknowledge support from the Imperial National Institute for Health Biomedical Research Centre and Cancer Research UK Imperial Experimental Cancer Medicine Centre. NJS is partly supported by an NIHR Senior Investigator award. JCR has nothing to disclose. IN has nothing to disclose. RAF has nothing to disclose. DS has nothing to disclose. JE has nothing to disclose. MW has nothing to disclose. PMS has nothing to disclose. NS has nothing to disclose. BWH has nothing to disclose. JT has nothing to disclose.

The national registration and treatment service for molar pregnancies in the UK allows for the collection of accurate data on this relatively rare diagnosis. In England and Wales, between 2000 and 2009, 5,793 patients with complete moles and 7,790 with partial moles were registered, compared with a total of 8,242,511 conceptions. The overall molar pregnancy incidence was 1 for every 607 conceptions (complete mole 1:1,423; partial mole 1:1,058), but with major variations with age. For complete moles, the risk varied from < 1:1,000 for ages 18-40, to 1:156 for women aged 45 and 1:8 for those aged 50 and above. The overall risk of requiring chemotherapy after a complete mole was 13.6% and 1.1% for partial mole, while the risk of a further molar pregnancy in the next conception was 1:68 but each of these figures have considerable variations with age. These modern statistics on molar pregnancy risks and outcomes should be of value to clinicians and their patients, while discussing this rare diagnosis.

Objective To determine whether oestradiol or follicle-stimulating hormone (FSH) measured prior to treatment could improve the predictive value of the risk score used to determine treatment in cases of persistent gestational trophoblastic disease (GTD). Design Prospective observational study. Setting Tertiary referral centre for GTD. Population All women referred to Weston Park Hospital, Sheffield, with GTD between 1st January 1996 and 31st December 2000. Methods Blood was taken prior to the initiation of treatment to measure oestradiol and FSH. The results were analysed with respect to the time taken for the β-hCG to return to normal. Main outcome measures Time taken to reach a normal β-hCG. Results Data on 118 women were collected. Three women died of GTD during follow up. Using Cox's proportional hazards regression analysis, division of the risk scores into high and low risk groups (≤7, >7) demonstrated a significant difference with regard to the length of time taken to reach a normal β-hCG level (hazard ratio 0.32; 95% CI: 0.18, 0.57) comparing high risk relative to low risk. However, addition of neither oestradiol nor FSH to the Cox regression analysis produced a significant hazard ratio (Ln oestradiol, 0.95; FSH 0.99). Division of the patients' risk scores into three groups of low (0–4), intermediate (5–7) and high (>7) risk groups produced similar results. Conclusions The measurement of neither oestradiol nor FSH appears to improve the prediction of outcome in persistent GTD when added to the risk score.

To evaluate the role of second (and third) uterine evacuation in the management of persistent gestational trophoblastic disease (GTD).This was an observational study of all cases registered over a 10-year period at the Trophoblastic Disease Centre at Weston Park Hospital, Sheffield. Five hundred and forty-four of 4050 women registered during 1991-2000 underwent a second uterine evacuation following a presumptive diagnosis of persistent GTD. The reason for evacuation, hCG level prior to the procedure, histological appearances of evacuated products and the clinical outcome (in terms of the need for chemotherapy) were determined.After a second uterine evacuation 368 patients (68%) completed the follow-up programme without further evidence of persistent disease or need for chemotherapy. If the diagnosis of persistent GTD was confirmed solely on the basis of elevated hCG levels then 171 of 282 (60%) patients did not require chemotherapy. Chemotherapy was more likely where there was histological evidence of persistent trophoblastic disease and where the urinary hCG was1500 IU/L at the time of the repeat evacuation. Twenty-eight of 60 patients (46%) undergoing a third evacuation required chemotherapy.Second uterine evacuation can be a useful therapeutic option for patients with presumed persistent trophoblastic disease not mandating immediate chemotherapy, particularly where the hCG level is1500 IU/L. Patients with documented persistent trophoblastic disease on histological examination of the second evacuation sample are more likely to require chemotherapy. Third evacuation is not now recommended.

Objective To determine the incidence and trends of gestational trophoblastic disease in the Asian population of Northern England and North Wales. Design A prospective observational study. Setting Trophoblastic Screening and Treatment Centre, Weston Park Hospital. Population A total of 3660 women registered with gestational trophoblastic disease between 1991 and 1999. Main outcome measures 1. The incidence of gestational trophoblastic disease in Asian and non-Asian population. 2. Trend in incidence over study period. Results Three hundred and twenty-two Asian patients were registered. The incidence of gestational trophoblastic disease in the northern part of England and Wales averaged 1 per 714 live births. The incidence of gestational trophoblastic disease in the Asian population was 1.95 times higher than in the non-Asian population (1 per 387 live births vs 1 per 752 live births). There was an excess of molar pregnancies in the extreme maternal age groups; the incidence in these women was twice as high as in the whole reproductive cohort. The ratio of partial to complete hydatidiform mole increased from 0.9 in the lower age to 2.6 in the older age group. There appeared to be a slowly rising trend in the incidence of gestational trophoblastic disease; the increase was higher in the Asian than in the non-Asian population. The ratio of partial to complete moles increased with age in both populations. Conclusions Asian women are at increased risk of having molar pregnancies. Molar pregnancies are more common at the extremes of reproductive age. The setting up of regional or national registration centres has helped to provide more accurate estimates of the true incidence of the disease.

Background: Gestational trophoblastic disease (GTD) is a rare complication of pregnancy, ranging from molar pregnancy to choriocarcinoma. Patients with persistent disease require treatment with chemotherapy. For the vast majority, prognosis is excellent. Occasionally, GTD is complicated by hyperthyroidism, which may require treatment. This is thought to occur due to molecular mimicry between human chorionic gonadotrophin (HCG) and thyroid-stimulating hormone (TSH), and hence cross-reactivity with the TSH receptor. Hyperthyroidism usually resolves as the GTD is successfully treated and correspondingly HCG levels normalise.\ud \ud Methods: This paper reviews cases of GTD treated over a 5-year period at one of the three UK centres and identifies the prevalence of hyperthyroidism in this population. Four cases with clinical hyperthyroidism are discussed.\ud \ud Results: On review of the 196 patients with gestational trophoblastic neoplasia treated with chemotherapy in Sheffield since 2005, 14 (7%) had biochemical hyperthyroidism. Of these, four had evidence of clinical hyperthyroidism.\ud \ud Conclusion: Concomitant biochemical thyroid disease in patients with GTD is relatively common, and measurement of thyroid function in patients with persistent GTD is, therefore, important. The development of hyperthyroidism is largely influenced by the level of HCG and disease burden, and usually settles with treatment of the persistent GTD. However, rarely the thyroid stimulation can have potentially life-threatening consequences.

To evaluate the Sheffield Trophoblastic Tumour Centre protocol for central nervous system (CNS) involvement in high-risk patients with gestational trophoblastic neoplasia (GTN) and determine the impact of brain imaging and lumbar puncture (LP) results on subsequent clinical care.The trophoblastic tumor database was searched for patients fitting any of the following criteria registered between January 1, 1988, and December 31, 2008: hCG levels50,000 IU/L, high risk,or = 2 for metastases. Placental site trophoblastic tumors (PSTTs) were excluded, and all patients with signs or symptoms suggestive of CNS involvement were investigated. Patients were to have computed tomography (CT) scan of the head and, if not contraindicated, LP to determine the ratio of cerebrospinal fluid to blood hCG level.A total of 154 patients metor = 1 of the defined criteria for CNS investigation. In 7 patients there was evidence of CNS involvement on CT. Only 2 cases had no clinical evidence of CNS disease-both had very-high-risk choriocarcinoma. No diagnosis of CNS disease was made on LP alone.We propose that in the absence of neurologic symptoms or signs, only patients with choriocarcinoma need be screened. Magnetic resonance imaging head scan is preferred as the most sensitive and safe technology available.

Objective To study the effect of a change in disease scoring systems on the management of patients with gestational trophoblastic neoplasia (GTN) in our supra-regional treatment centre. Methods We reviewed disease characteristics and treatment outcomes in 632 GTN patients managed at our centre from 1973 to 2006. Two disease scoring systems were used sequentially, the Sheffield modification of the Charing Cross Scoring System (SCCSS) before 2000, and the revised FIGO/modified WHO system (FIGO 2000) thereafter. Results Using the SCCSS 573 (90.7%) patients were classified as low risk (LR) and 59 (9.3%) as high risk (HR). With FIGO 2000, 587 (92.9%) were LR and 45 (7.1%) HR. For LR patients, the complete response (CR) to first line single agent chemotherapy was 77% before 2000 and 61.6% from 2000 to 2006. For HR patients, the CR rates with first line chemotherapy were 79.5% and 75% respectively. The higher threshold for assigning a patient as HR using FIGO 2000 had an impact on the success of treatment; only 7/19 patients (37%) who were scored 6 by FIGO 2000, and thus treated as LR with methotrexate/folinic acid, achieved a CR. Conclusion In our experience, the revised FIGO/modified WHO scoring system has down scored some patients who would have been considered as high risk with the previous scoring system. A trend to lower CR with first line chemotherapy and an increase in the need for second line chemotherapy was seen.

To determine the clinical presentation and outcome of postpartum choriocarcinoma.Case note review of patients with choriocarcinoma treated at the Sheffield Trophoblastic Disease Centre.Thirty-five patients were identified between 1977 and 2005. Mean age was 27 years (range, 21-37). Thirty-three patients complained of persistent postpartum hemorrhage, and in 3 cases there were other symptoms. Two patients presented with nongynecologic symptoms. Mean time until diagnosis was 7 weeks postpartum (range, 0-60), with a mean delay from onset of symptoms to treatment of 7 weeks (maximum, 19). Twenty patients had metastatic disease, but this did not correlate with delay in diagnosis. The mean International Federation of Gynecology and Obstetrics score was 10. Multidrug regimens were used in most patients; however, 8 low-risk patients had a complete response with methotrexate alone. The mean survival was 7.8 years (range, 1-21). Two patients died from disease.Postpartum choriocarcinoma presents mainly with vaginal bleeding, and there is often a delay in diagnosis despite being under the care of gynecologists. In the small numbers that present with nongynecologic symptoms there is a rapid awareness of the possibility of gestational trophoblastic neoplasia; nevertheless, the outcome may be fatal, especially in the presence of symptomatic brain metastases.

Objective. To describe the clinical features, treatment and outcome of all consecutive patients with placental site trophoblastic tumour (PSTT) treated at the Sheffield Trophoblast Centre and to compare these findings to other reports. Method. All cases of PSTT on the Sheffield Trophoblastic Tumour Centre database from 1984 to 2004 were reviewed. Data obtained included age at diagnosis, antecedent pregnancy (AP), interval from antecedent pregnancy until diagnosis, presenting features, presenting serum human chorionic gonadotrophin hormone (hCG) level, number and sites of metastases, treatment received, outcome and follow-up. Results. Seventeen patients with PSTT were identified from the database which incorporates a total of 7489 cases of trophoblastic disease. Fourteen (70.6%) were more than 30 years old at presentation; 5 were over 40. The median interval from pregnancy to diagnosis was 18 months (range 6 months to 22 years). The outcome of antecedent pregnancy was a female in 11 out of the 13 patients where the sex was known. Eleven (70.6%) of patients presented with irregular vaginal bleeding, with or without a preceding period of amenorrhoea. All 8 patients with non-metastatic (Stage I) disease were alive and well after hysterectomy (6), chemotherapy alone (1) or hysterectomy and chemotherapy (1) whereas only 4 of 9 patients with metastatic (Stage III/IV) disease were alive and well after treatment with chemotherapy and hysterectomy. Conclusion. PSTT is rare and accounts for 0.23% cases of gestational trophoblastic disease referred to this centre. It has a variety of presenting features and its course is unpredictable. Metastatic involvement and antecedent pregnancy interval greater than 4 years are poor prognostic factors. Hysterectomy is the primary mode of treatment in the majority of cases. However, chemotherapy can still play a major role when curative surgery is not feasible.

This study evaluated the immunogenicity and reactogenicity of a group C meningococcal conjugate vaccine (MenC) compared with a group A+C meningococcal polysaccharide vaccine (MenPS) in healthy adolescents. Subjects were randomised to receive one dose of either MenC (n=92) or MenPS (n=90). Group C meningococcal IgG antibody concentrations and bactericidal titres were higher in the MenC group than the MenPS group at 1 month (22.8 U/ml vs 4.0 U/ml, p

To describe the evolution of a highly regarded and unique model of multidisciplinary care providing support, monitoring, and treatment for all gestational trophoblastic disease (GTD) patients referred to Sheffield Trophoblastic Disease Centre, 1 of the 3 United Kingdom (UK) supraregional GTD centers.The UK GTD service was first established in 1973 and since its inception has centralized care for GTD patients and played a leading international role in developing therapies, management protocols, and biomarker assays with good outcomes for patients. The service preceded recent trends towards centralization for rare cancers in the U.K. In Sheffield the GTD team has evolved to become a true multidisciplinary team with a strong nursing component, which is set to expand in the future.Centralization of care for GTD in the U.K. has been directly associated with the impressive results the service has achieved, with high cure rates (98-100%) and low (5-8%) chemotherapy rates. The addition of GTD nurse specialists has been beneficial to patients as they provide a communication link between patients and their clinicians and ensure that information, support, and advice is available for all GTD patients, both in hospital and at home.The UK GTD service is an internationally renowned, multidisciplinary organization. The service achieves impressive clinical results and now features a strong nursing component. The addition of nurse specialists has enabled the team to offer both clinical and psychological care and means that specialist advice is available for patients and healthcare professionals involved in giving care to this patient group.