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Publications (9)24.65 Total impact

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    ABSTRACT: Gestational trophoblastic neoplasia (GTN) persisting despite local treatment requires chemotherapy. In 2000, the revised International Federation of Gynaecology and Obstetrics (FIGO)/World Health Organisation (WHO) staging system was introduced, classifying patients as at 'low' or 'high' risk for resistance to single agent treatment. We have evaluated the complete response rates of patients with low risk GTN treated with 2 weekly intramuscular (IM) methotrexate 50mg four doses days 1, 3, 5, 7 and oral folinic acid 15mg days 2, 4, 6, 8 (MTX/FA). Patient data between January 2000 and December 2011 were collated and the relationships between FIGO/WHO risk score and outcomes evaluated. Two hundred and eighty nine patients were treated with single agent IM MTX/FA and assessed for treatment response. 29/36 (81%) patients with a FIGO/WHO total score of 6 developed resistance to MTX/FA compared with 87/253 (34%) patients with a score of 0-5 (p⩽0.0001). Significantly higher rates of resistance were found for patients with an hCG level of >100,000iu/l compared to an hCG level of <100,000iu/l (84% versus 34% p⩽0.0001). All patients were eventually cured with chemotherapy or surgical salvage. Patients with low risk GTN that have a FIGO/WHO score of 6 or hCG level of >100,000iu/l have high rates of resistance to MTX/FA and require further treatment. Revision of the FIGO/WHO scoring system may be appropriate to enable selection of more effective first line chemotherapy.
    European journal of cancer (Oxford, England: 1990) 07/2013; · 4.12 Impact Factor
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    ABSTRACT: 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.
    Journal of obstetrics and gynaecology: the journal of the Institute of Obstetrics and Gynaecology 05/2013; 33(4):406-11. · 0.43 Impact Factor
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    ABSTRACT: 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. 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. 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. 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.
    British Journal of Cancer 05/2011; 104(11):1665-9. · 5.08 Impact Factor
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    ABSTRACT: 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 levels > 50,000 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 met > or = 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.
    The Journal of reproductive medicine 01/2010; 55(7-8):301-4. · 0.75 Impact Factor
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    ABSTRACT: 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.
    The Journal of reproductive medicine 11/2006; 51(10):819-24. · 0.75 Impact Factor
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    ABSTRACT: 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). Prospective observational study. Tertiary referral centre for GTD. All women referred to Weston Park Hospital, Sheffield, with GTD between 1st January 1996 and 31st December 2000. 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 beta-hCG to return to normal. Time taken to reach a normal beta-hCG. 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 beta-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. The measurement of neither oestradiol nor FSH appears to improve the prediction of outcome in persistent GTD when added to the risk score.
    BJOG An International Journal of Obstetrics & Gynaecology 07/2005; 112(7):977-80. · 3.76 Impact Factor
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    ABSTRACT: The aim of the study was to record the incidence of treatment for infertility prior to development of gestational trophoblastic disease (GTD). A retrospective analysis was undertaken of 231 consecutive women receiving chemotherapy for persistent GTD at Weston Park Hospital, Sheffield, from 1991 to 2001. Three patients in this group had received treatment for infertility prior to their molar pregnancy. In a control group of 226 patients not requiring treatment for persistent GTD, four had had treatment for infertility just before their molar pregnancy, and in a further control group of 208 'normal' pregnancies, eight patients had had treatment for infertility prior to conception. We conclude that we can demonstrate no relationship between infertility treatment and subsequent development of GTD.
    Human Reproduction 03/2004; 19(2):365-7. · 4.67 Impact Factor
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    ABSTRACT: The aim of this study was to evaluate the efficacy and toxicity of low-dose methotrexate with folinic acid rescue in a large series of consecutively treated patients with low-risk persistent gestational trophoblastic disease. Between January 1987 and December 2000, 250 patients were treated with intramuscular methotrexate (50 mg on alternate days 1, 3, 5, 7) with folinic acid (7.5 mg orally on alternate days 2, 4, 6, 8) rescue. The overall complete response rate without recurrence was 72% for first-line treatment and 95% for those who required second-line chemotherapy. Eight women (3.2%) had recurrence following remission and two (0.8%) had new moles. Two women (0.8%) died of their disease giving an overall cure of 99%. Only 10 women (4%) experienced grade III/IV toxicity during the first course of treatment and 13 women (5.2%) subsequently. Toxicity included mucositis and stomatitis, pleuritic chest pain, thrombocytopenia, uterine bleeding, abdominal pain, liver function changes, rash and pericardial effusion. A total of 59 women (23.6%) required second-line chemotherapy; 48 women had methotrexate resistance, eight had methotrexate toxicity and an empirical decision to change therapy was made in three. In all, 11 women (4.4%) had a hysterectomy before, during or after treatment; 141 women (56.4%) became pregnant following treatment: in 128 (90.7%), the outcome was successful. Methotrexate with folinic acid rescue is an effective treatment for low-risk persistent trophoblastic disease. It has minimal severe toxicity, excellent cure rates and does not appear to affect fertility.
    British Journal of Cancer 01/2004; 89(12):2197-201. · 5.08 Impact Factor
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    ABSTRACT: Spontaneously occurring primary pneumothorax in the young is uncommon but well documented as a complication of primary or secondary lung malignancy. We report the case of a 24-year-old female patient with placental site trophoblastic tumour presenting as recurrent pneumothorax, despite initial surgery and chemotherapy. Later, despite further chemotherapy, she developed conjunctival metastasis. To the best of our knowledge, this is the first case of a placental site trophoblastic tumour metastasising to the conjunctiva to be reported in the literature. Clinicians should keep in mind the possibility of pneumothorax due to lung metastasis when no obvious primary lung disorder is apparent.