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1.
Gynecol Oncol ; 172: 47-53, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36934478

RESUMO

OBJECTIVES: Gestational Trophoblastic Neoplasia (GTN) is a rare group of malignant placental-related tumours requiring systemic anti-cancer treatment. Leptomeningeal disease (LMD) related to GTN is not well reported with no consensus in optimal treatment. We offer recommendations for management of these patients. METHODS: We discuss five patients with GTN who presented with features of LMD and were diagnosed with gadolinium-enhanced MRI brain, all of whom received low dose induction etoposide-cisplatin (EP) followed by either EP-etoposide, methotrexate (CNS) and actinomycin-D (EMA) or EMA(CNS)-cyclophosphamide and vincristine (CO). RESULTS: Four out of the five patients additionally received intrathecal methotrexate. Four patients had complete hCG response to first line multi-agent chemotherapy, one patient required second line paclitaxel, cisplatin alternating with paclitaxel, etoposide (TP/TE), where paclitaxel was substituted with nab-paclitaxel due to anaphylaxis, followed by hysterectomy. One of the four initial complete hCG responders relapsed in the lung requiring further systemic treatment with subsequent lobectomy. Patient reported outcomes indicate persistent neurological symptoms are mild and do not affect functionality and quality of life. CONCLUSION: With a follow-up range of 2-6 years, all five patients remain cured demonstrating excellent survival outcomes with the avoidance of whole-brain radiotherapy in all cases.


Assuntos
Cisplatino , Doença Trofoblástica Gestacional , Gravidez , Humanos , Feminino , Etoposídeo , Metotrexato , Qualidade de Vida , Placenta/patologia , Doença Trofoblástica Gestacional/terapia , Doença Trofoblástica Gestacional/tratamento farmacológico , Dactinomicina , Ciclofosfamida , Vincristina , Paclitaxel/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos Retrospectivos
2.
BJOG ; 127(10): 1260-1267, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32279427

RESUMO

OBJECTIVE: To establish the prevalence of high-grade cervical intraepithelial neoplasia (CIN2+) in women referred to colposcopy with persistent high-risk human papillomavirus (hrHPV) cytology-negative screening sample according to hrHPV genotype, age at referral and colposcopic performance. DESIGN: Prospective cohort study. SETTING: Single colposcopy clinic linked to a population-based screening programme. POPULATION: Women referred with persistent hrHPV cytology-negative routine screening samples. METHODS: Prospective study with descriptive statistics from a single colposcopy unit between June 2014 and July 2019. MAIN OUTCOME MEASURES: Prevalence of hrHPV genotypes and CIN2+, positive predictive value for colposcopic impression, and inadequate colposcopic examinations. RESULTS: A total of 3107 women were referred. Prevalence of CIN2+ was highest for persistent HPV16 infections (10.7%) compared with HPV18 (3.6%) or HPVO (4.7%). Prevalence of CIN2+ declined with age (25-34 years 14.2% to 55-64 years 1.1%) whereas the percentage of women with an inadequate colposcopic examination increased (25-34 years 0.9% to 55-64 years 29.5%). High-grade colposcopic impression fell over time during the study from 16.1 to 5.1%. The positive predictive value for colposcopic impression of CIN2+ was affected by hrHPV genotype (57.3% for HPV16 versus 32.1% for nonHPV16). The adjunctive use of electrical impedance spectroscopy detected an extra 42 cases of CIN2+, which was irrespective of hrHPV genotype. CONCLUSIONS: Primary hrHPV cervical screening increases detection of CIN2+; however, low specificity results in more women being referred to colposcopy with a low prevalence of CIN2+. Colposcopy performs poorly in some groups, particularly with HPVO infections and women over 50 years of age. An appropriate threshold for referral to colposcopy in primary hrHPV screening has not been established. TWEETABLE ABSTRACT: Low prevalence of CIN2+ in HPV-positive negative cytology samples. HPV genotype, age and prevalence of CIN2+ affect colposcopic performance.


Assuntos
Colposcopia/normas , Infecções por Papillomavirus/epidemiologia , Displasia do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Adulto , Fatores Etários , Colposcopia/estatística & dados numéricos , Feminino , Humanos , Programas de Rastreamento/estatística & dados numéricos , Pessoa de Meia-Idade , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Prevalência , Estudos Prospectivos , Sensibilidade e Especificidade , Neoplasias do Colo do Útero/diagnóstico , Adulto Jovem , Displasia do Colo do Útero/diagnóstico
3.
BJOG ; 127(9): 1102-1107, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32146729

RESUMO

OBJECTIVE: To investigate the demographics, natural history and treatment outcomes of non-molar gestational choriocarcinoma. DESIGN: A retrospective national population-based study. SETTING: UK 1995-2015. POPULATION: A total of 234 women with a diagnosis of gestational choriocarcinoma, in the absence of a prior molar pregnancy, managed at the UKs two gestational trophoblast centres in London and Sheffield. METHODS: Retrospective review of the patient's demographic and clinical data. Comparison with contemporary UK birth and pregnancy statistics. MAIN OUTCOMES: Incidence statistics for non-molar choriocarcinoma across the maternal age groups. Cure rates for patients by FIGO prognostic score group. RESULTS: Over the 21-year study period, there were 234 cases of non-molar gestational choriocarcinoma, giving an incidence of 1:66 775 relative to live births and 1:84 226 to viable pregnancies. For women aged under 20, the incidence relative to viable pregnancies was 1:223 494, for ages 30-34, 1:80 227, and for ages 40-45, 1:41 718. Treatment outcomes indicated an overall 94.4% cure rate. Divided by FIGO prognostic groups, the cure rates were low-risk group 100%, high-risk group 96% and ultra-high-risk group 80.5%. CONCLUSIONS: Non-molar gestational choriocarcinoma is a very rare diagnosis with little prior detailed information on the demographics and natural history. The data in this study give age-related incidence data based on a large national population study. The results also demonstrated the widely varying natural history of this rare malignancy and the marked correlation of disease incidence with rising maternal age. TWEETABLE ABSTRACT: National gestational choriocarcinoma database indicates a close association between increasing maternal age and incidence.


Assuntos
Coriocarcinoma/epidemiologia , Neoplasias Uterinas/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Coriocarcinoma/complicações , Coriocarcinoma/secundário , Coriocarcinoma/terapia , Feminino , Número de Gestações , Humanos , Incidência , Nascido Vivo/epidemiologia , Idade Materna , Pessoa de Meia-Idade , Gravidez , Complicações Neoplásicas na Gravidez/epidemiologia , Complicações Neoplásicas na Gravidez/patologia , Complicações Neoplásicas na Gravidez/terapia , Prognóstico , Fatores de Risco , Resultado do Tratamento , Reino Unido/epidemiologia , Hemorragia Uterina/etiologia , Neoplasias Uterinas/complicações , Neoplasias Uterinas/patologia , Neoplasias Uterinas/terapia , Adulto Jovem
4.
J Electr Bioimpedance ; 11(1): 81-86, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33584907

RESUMO

OBJECTIVE: Colposcopy can be used with Electrical Impedance Spectroscopy (EIS) as an adjunct, to assess the presence of High Grade Cervical Intra-epithelial Neoplasia (CIN2+). This analysis of longitudinal data has used the results from women with a negative colposcopy, in order to see if the initial (index) EIS results were able to predict the women who subsequently developed CIN2+. A further objective was to investigate what tissue structural changes might be reflected in the electrical impedance spectra. METHODS: 847 patients were referred with low grade cytologly. EIS measurements were made around the transformation zone of the cervix during colposcopy. Every EIS spectrum was matched to a template representing CIN2+ and the result was positive if the match exceeded a probability index threshold. The colposcopic impression was also recorded. All the women who developed biopsy proven CIN2+ within three years of the index colposcopy were identified. RESULTS: The median follow-up was 30.5 months. Where both CI and EIS were initially positive, there was an increased prevalence (8.13%) of CIN2+ developing as opposed to 3.45% in the remaining patients (p=0.0159). In addition, if three or more EIS spectra were positive there was a higher prevalence (9.62% as opposed to 3.56% p=0.0132) of CIN2+ at three years. The index spectra recorded from the women who developed CIN2+ showed EIS changes consistent with increases in the extracellular volume and in cell size inhomogeneity. CONCLUSION: EIS does offer prognostic information on the risk of CIN2+ developing over the three-year period following the EIS measurements. The changes in EIS spectra are consistent with an increase in cell size diversity as pre-malignancy develops. These changes may be a consequence of increased genetic diversity as neoplasia develops.

6.
Eur J Cancer ; 109: 162-171, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30731277

RESUMO

OBJECTIVE: The objective of the study was to evaluate the effect of high-dose chemotherapy (HDC) with peripheral blood stem cell support (PBSCS) on survival of patients with gestational trophoblastic neoplasia (GTN) with either refractory choriocarcinomas or a poor-prognosis placental site/epithelioid trophoblastic tumours (PSTT/ETTs). METHODS: Databases of two referral centres for gestational trophoblastic disease were searched, and 32 patients treated with HDC between 1994 and 2015 were identified. Tissue samples were retrieved for genetic evaluation. Cox regression analyses were performed to identify possible predictors of overall survival (OS). RESULTS: HDC induced a sustained complete response in 7 patients. Overall, 41% (13/32) of the patients remained disease free after HDC with or without additional treatment. Patients who survived had much lower human chorionic gonadotropin (hCG) values (all ≤12 IU/L) before and after HDC than those who died of disease. Univariable Cox regression analysis demonstrated that hCG >12 IU/L before or after HDC, International Federation of Gynaecology and Obstetrics (FIGO) stage II-IV and presence of metastases at the time of diagnosis were significantly associated with adverse OS. However, only hCG values before HDC remained significant in a multivariable model (p < 0.001). Five of 11 (45%) patients with PSTT/ETT presenting ≥48 months after antecedent pregnancy and 6 of 14 (43%) patients with refractory choriocarcinoma were in remission. Three treatment-related deaths occurred. CONCLUSIONS: Despite 3 treatment-induced deaths, HDC with PBSCS appears to be active in salvaging selected patients with poor-prognosis PSTT/ETTs and refractory choriocarcinomas. Low hCG values before HDC seems a beneficial predictor of OS and may suggest that HDC acts more like a consolidation therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença Trofoblástica Gestacional/terapia , Transplante de Células-Tronco de Sangue Periférico/mortalidade , Complicações Neoplásicas na Gravidez/terapia , Adulto , Terapia Combinada , Feminino , Seguimentos , Doença Trofoblástica Gestacional/patologia , Humanos , Pessoa de Meia-Idade , Gravidez , Complicações Neoplásicas na Gravidez/patologia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
7.
Eur J Obstet Gynecol Reprod Biol ; 234: 117-119, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30684876

RESUMO

OBJECTIVE: To determine whether post-pregnancy human chorionic gonadotrophin screening after previous hydatidiform mole identifies patients with recurrent gestational trophoblastic disease. STUDY DESIGN: A retrospective evaluation of 9315 patients who underwent post-pregnancy screening from 2000 to 2009, as part of the National Gestational Trophoblastic Disease Service in the UK. RESULTS: Patients with previous hydatidiform mole, who had human chorionic gonadotrophin screening after one or more subsequent pregnancies, were identified (n = 9315). Of these, 8630 patients had an initial hydatidiform mole that did not require chemotherapy. In 12,329 subsequent pregnancy events, screening with human chorionic gonadotrophin identified 3 cases of gestational trophoblastic neoplasm. The remaining 685 patients developed gestational trophoblastic neoplasm, following their initial hydatidiform mole and required chemotherapy. In this group there were 1012 further pregnancy events, human chorionic gonadotrophin screening identified 3 patients with gestational trophoblastic neoplasm. The overall recurrence rate was 6 in 13,341 events (risk 1: 2227). The rate was 3 in 12,329 (risk 1:4110) for HM that did not require chemotherapy and 3 in 1012 (1:337) for previously treated gestational trophoblastic neoplasm. All 6 patients with recurrent disease were successfully treated with chemotherapy. CONCLUSION: Routine post-pregnancy human chorionic gonadotrophin screening may be safely discontinued in patients with one previous uncomplicated hydatidiform mole.


Assuntos
Gonadotropina Coriônica/sangue , Doença Trofoblástica Gestacional/diagnóstico , Mola Hidatiforme/sangue , Recidiva Local de Neoplasia/diagnóstico , Neoplasias Uterinas/sangue , Adulto , Feminino , Doença Trofoblástica Gestacional/etiologia , Humanos , Mola Hidatiforme/complicações , Recidiva Local de Neoplasia/etiologia , Período Pós-Parto/sangue , Gravidez , Estudos Retrospectivos , Fatores de Risco , Neoplasias Uterinas/complicações
8.
Gynecol Oncol ; 152(2): 361-367, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30473257

RESUMO

OBJECTIVE: Epithelioid Trophoblastic Tumor (ETT) is an extremely rare form of Gestational Trophoblastic Neoplasia (GTN). Knowledge on prognostic factors and optimal management is limited. We identified prognostic factors, optimal treatment, and outcome from the world's largest case series of patients with ETT. METHODS: Patients were selected from the international Placental Site Trophoblastic Tumor (PSTT) and ETT database. Fifty-four patients diagnosed with ETT or mixed PSTT/ETT between 2001 and 2016 were included. Cox regression analysis was used to identify prognostic factors for overall survival (OS). RESULTS: Forty-five patients with ETT and 9 patients with PSTT/ETT were included. Thirty-six patients had FIGO stage I and 18 had stages II-IV disease. Patients were treated with surgery (n = 23), chemotherapy (n = 6), or a combination of surgery and chemotherapy (n = 25). In total, 39 patients survived, including 22 patients with complete sustained hCG remission for at least 1 year. Patients treated with surgery as first line treatment had early-stage disease and all survived. Most patients treated with chemotherapy with or without surgery had FIGO stages II-IV disease (55%). They underwent multiple lines of chemotherapy. Eleven of them did not survive. Interval since antecedent pregnancy and FIGO stage were prognostic factors of OS (p = 0.012; p = 0.023 respectively). CONCLUSIONS: Advanced-stage disease and an interval of ≥48 months since the antecedent pregnancy are poor prognostic factors of ETT. Surgery seems adequate for early-stage disease with a shorter interval. Advanced-stage disease requires a combination of treatment modalities. Because of its rarity, ETT should be treated in a centre with experience in GTN.


Assuntos
Neoplasias Trofoblásticas/diagnóstico , Neoplasias Trofoblásticas/terapia , Adulto , Bases de Dados Factuais , Células Epitelioides/patologia , Feminino , Humanos , Estadiamento de Neoplasias , Prognóstico , Neoplasias Trofoblásticas/patologia
9.
Cytopathology ; 29(2): 133-142, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29350424

RESUMO

INTRODUCTION: Primary HPV screening will be implemented into the English Cervical Screening Programme by 2019. Its impact upon women referred to colposcopy, with negative cytology but persistently positive high-risk HPV (hrHPV), remains unreported from UK Sentinel sites. HPV primary screening was introduced in Sheffield, UK in April 2013; this paper reports its impact on the service. METHODS: A retrospective cohort study was performed from June 2014 to July 2016 at the Jessop Wing Colposcopy Unit, Sheffield. UK. Data were obtained from the pathology and colposcopy databases and cross-referenced with case-notes and pathology results for women referred with persistently positive hrHPV, cytology negative samples. Patient demographics, hrHPV genotype, biopsy rates, histological diagnoses, management, and outcomes were collected and baseline statistics performed. RESULTS: During the study 1076 women were seen. Most frequent hrHPV genotypes were: hrHPV other, 41%; and HPV16, 33%. The majority (72%) were found to have normal colposcopy; 28% had an abnormal colposcopic assessment (11% low-grade; 11% high-grade; 6% inadequate). The majority were discharged (83%) and only 5% underwent LLETZ. No cancers were detected. High-grade cervical intraepithelial neoplasia (CIN) was found in 7%; overall risk of CIN2 was 1/29; 1/30 for CIN3. Presence of HPV16 was associated with a significantly higher risk of high-grade CIN; 1/9. CONCLUSION: This is the first study to report results for women referred to colposcopy with cytology negative, persistently positive hrHPV. Disease prevalence is low, although women with HPV16 have a significantly higher likelihood of high-grade disease compared to other HPV subtypes.


Assuntos
Genótipo , Papillomaviridae/genética , Infecções por Papillomavirus , Displasia do Colo do Útero , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Prevalência , Estudos Retrospectivos , Displasia do Colo do Útero/epidemiologia , Displasia do Colo do Útero/genética , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/virologia
10.
J Gynecol Obstet Hum Reprod ; 46(9): 669-673, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28866125

RESUMO

OBJECTIVES: To determine the efficacy of colposcopy plus ZedScan, which measures changes in tissue electrical impedance, for detecting intraepithelial high-grade lesions compared to colposcopy alone. METHODS: A prospective study conducted at a university hospital colposcopy clinic. Patients referred following abnormal cervical cytology or colposcopic follow up were examined by colposcopy plus ZedScan to assess the cervix. The results of ZedScan directed and colposcopically directed biopsies were compared. RESULTS: Ninety-one patients were included in this study. The median age was 33 years. Eighty (88%) were referred with abnormal cytology; LSIL 45%, ASCUS 27%, ACS-H 8%, HSIL 7%, AGC 1% and 12% follow-up postconisation or colposcopic follow up. Colposcopy alone detected 18 high-grade lesions with 64 women undergoing biopsy with a total of 115 biopsies being taken with a sensitivity of 60% and NPV estimated at 81.7%. ZedScan with colposcopy increased the detection of high-grade lesions by 47.3%, identifying 27 high-grade lesions and one case of invasive cancer. Sensitivity was 93.1% and NPV estimated at 91.3%. A combination of normal colposcopy practice and ZedScan had a sensitivity and NPV of 100%. CONCLUSION: ZedScan used in conjunction with the colposcopy improves sensitivity in detecting high-grade lesions at the expense of a moderate increase in the number of biopsies.


Assuntos
Carcinoma de Células Escamosas/diagnóstico , Colposcopia/métodos , Espectroscopia Dielétrica , Neoplasias do Colo do Útero/diagnóstico , Adulto , Biópsia , Carcinoma de Células Escamosas/patologia , Colo do Útero/diagnóstico por imagem , Colo do Útero/patologia , Citodiagnóstico , Detecção Precoce de Câncer/métodos , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Valor Preditivo dos Testes , Prognóstico , Neoplasias do Colo do Útero/patologia , Adulto Jovem
11.
Cytopathology ; 28(5): 407-412, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28752640

RESUMO

BACKGROUND: The Jessop Wing Colposcopy Unit identified that between 1st April 2014 and 31st March 2015 the number of women referred with high-grade dyskaryosis and the number of women undergoing treatment increased by 21% and 19%, respectively. There was concern that referral and treatment rates were increasing because we were now seeing women, previously discharged to routine recall with prior low-grade cytology hrHPV positive, re-enter the system for their second round of screening. The aim of this study was to assess the reasons for our significant increase in referral and treatment rates. METHODS: A retrospective cohort study performed between 1st April 2012 and 30th June 2015 at the Jessop Wing Colposcopy Unit, Sheffield, UK. RESULTS: During the study period, 1765 women underwent large loop excision of the transformation zone (LLETZ), of whom 1517 were referred with high-grade dyskaryosis. Fifty-six (4%) women undergoing treatment; and four untreated high-grade referrals were seen in the previous 3-5 years with low-grade cytology hrHPV positive and discharged to routine recall. There were no cases of invasive disease in the previously discharged groups. There was, however, a significantly higher likelihood of a negative LLETZ (P=.0066) in those women previously discharged to routine recall, and lower rates of CIN2 or worse identified. CONCLUSION: Prior discharge to routine recall does not have any major influence on treatment rates or high-grade referrals. The finding of no invasive disease; lower rates of CIN2 or worse; and a significantly higher likelihood of a negative LLETZ in those women previously discharged to routine recall is reassuring and further reinforces the safety of HPV triage pathways.


Assuntos
Colposcopia , Citodiagnóstico , Infecções por Papillomavirus/diagnóstico , Displasia do Colo do Útero/diagnóstico , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/cirurgia , Infecções por Papillomavirus/virologia , Gravidez , Resultado do Tratamento , Triagem , Esfregaço Vaginal , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/cirurgia , Displasia do Colo do Útero/virologia
12.
Cancer Treat Rev ; 56: 47-57, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28482228

RESUMO

The classification system for Gestational trophoblastic neoplasia (GTN) has proved a controversial topic for over 100years. Numerous systems simultaneously existed in different countries, with three main rival classifications gaining popularity, namely histological, anatomical and clinical prognostic systems. Until 2000, prior to the combination of the FIGO and WHO classifications, there was no worldwide consensus on the optimal classification system, largely due to a lack of high quality data proving the merit of one system over another. Remarkably, a validated, prospectively tested classification system is yet to be conducted. Over time, increasing criticisms have emerged regarding the currently adopted combined FIGO/WHO classification system, and its ability to identify patients most likely to develop primary chemotherapy resistance or disease relapse. This is particularly pertinent for patients with low-risk disease, whereby one in three patients are resistant to first line therapy, rising to four out of five women who score 5 or 6. This review aims to examine the historical basis of the GTN classification systems and critically appraise the evidence on which they were based. This culminates in a critique of the current FIGO/WHO prognostic system and discussion surrounding clinical preference versus evidence based practice.


Assuntos
Doença Trofoblástica Gestacional/classificação , Resistencia a Medicamentos Antineoplásicos , Feminino , Doença Trofoblástica Gestacional/tratamento farmacológico , Doença Trofoblástica Gestacional/patologia , Humanos , Gravidez
13.
Gynecol Oncol ; 143(3): 565-570, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27756557

RESUMO

OBJECTIVE: To evaluate the outcome of patients treated with second-line chemotherapy for methotrexate-resistant low-risk GTN at the Sheffield Centre, UK between 2001 and 2015, including the novel use of single-agent carboplatin as a strategy to reduce exposure to combination chemotherapy. METHODS: 392 low-risk GTN patients were treated with first-line methotrexate. The selection of chemotherapy regimen following methotrexate-resistance depended on the volume of residual disease as indicated by the serum hCG value at the time, with patients switching to either single-agent dactinomycin at an hCG level<150IU/L from 2001-2010 and <300IU/L since 2010, or to combination treatment with etoposide/dactinomycin (EA) above these thresholds. In order to reduce exposure to more toxic combination chemotherapy regimens, our treatment policy was revised in 2011, with the recommendation of single-agent carboplatin as an alternative to EA at hCG levels >300IU/L. RESULTS: 136 (35%) of 392 received second-line chemotherapy following methotrexate-resistance. 59 patients received single-agent dactinomycin with 53 (90%) patients achieving complete hCG response, 3 patients requiring combination chemotherapy or surgery, and 3 patients subsequently spontaneously resolving. 56 patients received EA chemotherapy with hCG complete response in 50 (89%) patients, and the remaining 6 patients were cured with further multi-agent chemotherapy or surgery. With carboplatin, 17/21 (81%) achieved an overall complete hCG response rate, with 4 patients requiring third-line EA. Carboplatin was well tolerated with no significant alopecia; myelosuppression was the most significant toxicity. Overall survival for all patients was 100%. CONCLUSION: These data show the continued excellent outcomes for methotrexate-resistant low-risk patients treated with single-agent dactinomycin or EA. Our experience with carboplatin is promising and provides an alternative regimen for methotrexate-resistant low-risk disease that avoids alopecia and in-patient treatment.


Assuntos
Antineoplásicos/uso terapêutico , Carboplatina/uso terapêutico , Dactinomicina/uso terapêutico , Doença Trofoblástica Gestacional/tratamento farmacológico , Neoplasias Uterinas/tratamento farmacológico , Adulto , Gonadotropina Coriônica/sangue , Resistencia a Medicamentos Antineoplásicos , Feminino , Doença Trofoblástica Gestacional/sangue , Humanos , Metotrexato , Neoplasia Residual , Gravidez , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Neoplasias Uterinas/sangue , Adulto Jovem
14.
BJOG ; 123(7): 1175-81, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26774079

RESUMO

OBJECTIVE: To determine the outcome of women with persistently raised but falling human chorionic gonadotrophin (hCG) levels 6 months after surgical evacuation of a molar pregnancy. DESIGN: An 11-year retrospective review. SETTING: The United Kingdom supra-regional trophoblastic disease treatment centres at Weston Park Hospital (Sheffield) and Charing Cross Hospital (London). POPULATION: Women with raised but falling serum human chorionic gonadotrophin (hCG) levels 6 months after evacuation of a molar pregnancy. METHODS: Retrospective case note review of eligible women identified by the electronic databases held at each supra-regional centre. MAIN OUTCOME MEASURES: The proportion of women that attain normal hCG levels spontaneously without chemotherapy. In addition, rates of gestational trophoblastic neoplasia (GTN), drug resistance, disease relapse and overall survival are reported. RESULTS: Thirty-five women with molar pregnancy and raised but falling serum hCG levels continued surveillance 6 months after evacuation. Levels of hCG in 30 of the patients (86%) fell to normal levels spontaneously. One woman defaulted follow up prior to hCG normalisation (3%) and the remaining four women (11%) were treated with chemotherapy due to a plateau or rise in serum hCG levels indicating GTN. All treated women were successfully salvaged by either first (n = 1) or second line (n = 2) chemotherapy or found to have persistently raised low level hCG of uncertain clinical relevance (n = 1). No women developed relapsed disease and overall survival was 100%. CONCLUSIONS: Women with a molar pregnancy and a raised but falling hCG level beyond 6 months from uterine evacuation can be safely observed with regular hCG monitoring and can usually avoid potentially toxic chemotherapy. TWEETABLE ABSTRACT: Women with treated molar pregnancy may avoid chemotherapy if 6-month hCG levels are raised but falling.


Assuntos
Mola Hidatiforme/cirurgia , Neoplasias Uterinas/cirurgia , Adulto , Antineoplásicos/uso terapêutico , Gonadotropina Coriônica/metabolismo , Feminino , Humanos , Mola Hidatiforme/tratamento farmacológico , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Regressão Neoplásica Espontânea , Gravidez , Terapia de Salvação/métodos , Neoplasias Uterinas/tratamento farmacológico , Adulto Jovem
15.
Cytopathology ; 27(3): 210-7, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26415635

RESUMO

OBJECTIVE: This study looks at the importance of large loop excision of the transformation zone (LLETZ) excision margins and residual cervical intraepithelial neoplasia (CIN) in women undertaking high-risk human papillomavirus (hrHPV) test of cure (TOC). METHODS: A retrospective cohort study with interval analysis performed June 2007 and June 2012 on all women undertaking treatment for CIN and subsequent hrHPV TOC 6 months post LLETZ. RESULTS: Final analysis group comprised 2093 women treated by LLETZ (1396 completely excised; 697 incompletely excised). 298 out of 1794 women (13%) were hrHPV positive at TOC. Thirty-six women who failed TOC and attended colposcopy had residual CIN. No statistically significant difference existed between the completely and incompletely excised groups with regards to the detection of residual CIN at 6 months post-treatment. There was no correlation of margins of excision with hrHPV status at TOC. The overall cure rate at TOC was 98%. CONCLUSIONS: TOC pathways recommend subsequent follow-up in primary care. This study identified no safety issues with TOC pathways. We can no longer assess histological failure rates at 12 months; we, therefore, recommend that this measure of treatment failure be redefined for post TOC women. It seems time to question the benefits of routine excision margins reporting, in the absence of invasion, for treated CIN. Future reporting needs to be reconsidered by the Royal College of Pathologists.


Assuntos
Colo do Útero/patologia , Margens de Excisão , Infecções por Papillomavirus/diagnóstico , Displasia do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adulto , Idoso , Colo do Útero/cirurgia , Colposcopia , Citodiagnóstico , Feminino , Humanos , Pessoa de Meia-Idade , Teste de Papanicolaou , Papillomaviridae , Gravidez , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia , Adulto Jovem , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/cirurgia
16.
J Obstet Gynaecol ; 36(3): 380-5, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26648096

RESUMO

This national audit assessed whether UK specialist vulval clinics adhere to the British Society of Vulval Diseases (BSSVD) document 'Standards of care for women with vulval conditions' published in 2013 and benchmarked clinician attitudes towards nurse practitioners in vulval services. Audit standards were based on the BSSVD guidance. All BSSVD and British Society for Colposcopy and Cervical Pathology or BSCCP members were surveyed via two electronic questionnaires. Results demonstrate that the majority of specialist vulval clinics in the UK are non-compliant with the standards set out for specialist vulval services. The majority of clinicians would support the introduction of clinical nurse specialists to vulval services, but there is need for development of a national training programme. In conclusion, significant improvements are required in provision of patient information, guidelines, access to multidisciplinary services, multidisciplinary team or MDT processes and data recording in UK specialist vulval services.


Assuntos
Atitude do Pessoal de Saúde , Profissionais de Enfermagem , Doenças da Vulva/terapia , Feminino , Humanos , Auditoria Médica/estatística & dados numéricos , Padrão de Cuidado , Reino Unido
17.
Cytopathology ; 26(6): 381-7, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25412857

RESUMO

OBJECTIVE: When the Sheffield screening laboratory changed the high-risk human papillomavirus (hrHPV) platforms from hybrid capture 2(®) (HC2; Digene Ltd) and to cobas 4800(®) (Roche) an unexpected and substantial increase in the number of cytology-negative/hrHPV-positive test-of-cure (ToC) samples after large loop excision of the transformation zone (LLETZ) was noted. We explore the potential reasons for these increased rates and discuss the implications this may have on the English NHS cervical screening programme (CSP). METHODS: A retrospective cohort study with interval analysis between June 2007 and June 2012. RESULTS: ToC was performed on 1530 women with HC2 and 396 with cobas 4800: 95.1% and 92.4% of women had negative cytology at ToC in the HC2 and cobas4800 testing period, respectively. Of these 13.9% and 27.8% tested positive for hrHPV in the HC2 and cobas 4800 group, respectively (P = <0.0001). No clinically significant increase in the number of cases of cervical intraepithelial neolpasia (CIN) was detected by the cobas4800 test in spite of doubling the number of cytology-negative/hrHPV-positive ToC samples. CONCLUSIONS: As far as we are aware, this is the first study reporting potential differences between different HPV platforms currently available in the English programme. The immediate impact of this increase in rates of hrHPV detection with cobas4800 is an increased number of colposcopy referrals to our service. The NHSCSP needs to assess whether this increase is acceptable and, if not, whether specific HPV platforms more suited to screening in a ToC scenario should be recommended.


Assuntos
Colo do Útero/patologia , DNA Viral/isolamento & purificação , Eletrocirurgia , Hibridização de Ácido Nucleico , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/patologia , Displasia do Colo do Útero/patologia , Neoplasias do Colo do Útero/patologia , Adolescente , Adulto , Idoso , Colo do Útero/cirurgia , Estudos de Coortes , Colposcopia , Detecção Precoce de Câncer , Inglaterra , Reações Falso-Negativas , Feminino , Humanos , Pessoa de Meia-Idade , Dados de Sequência Molecular , Infecções por Papillomavirus/diagnóstico , Estudos Retrospectivos , Sensibilidade e Especificidade , Neoplasias do Colo do Útero/diagnóstico , Adulto Jovem , Displasia do Colo do Útero/diagnóstico
18.
Gynecol Oncol ; 136(2): 258-63, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25542400

RESUMO

OBJECTIVE: To determine whether single agent chemotherapy with intramuscular methotrexate 50mg administered on days 1, 3, 5, and 7 and oral folinic acid 15mg administered on days 2, 4, 6, and 8 in 2 weekly cycles (IM MTX/FA) is an effective treatment regimen for patients with low risk gestational choriocarcinoma. METHOD: Electronic databases were searched to identify patients with gestational choriocarcinoma at the Sheffield and Charing Cross supra-regional trophoblastic disease centres from January 2000 to December 2011. Clinical notes of low risk patients with FIGO score 0-6 were retrospectively reviewed to assess treatment outcomes and subsequent relapse. RESULTS: 65 patients were identified with low risk choriocarcinoma. Serum hCG levels normalised in 24 patients without the requirement of chemotherapy (19 with histological confirmation, 4 highly suspicious histology and 1 clinical diagnosis). Of 23 patients with histologically confirmed choriocarcinoma, 8 (35%) had a sustained complete response to IM MTX/FA and did not relapse. Both patients with FIGO score 6, and 1 patient with FIGO stage III metastatic disease developed resistance to IM MTX/FA and required further treatment. Despite the development of drug resistance or relapse all patients were successfully salvaged by subsequent treatments. CONCLUSIONS: Not all patients with low risk choriocarcinoma that have had primary intervention prior to staging, such as surgical resection or uterine evacuation will require chemotherapy, providing hCG levels continue to decline to normal. Low risk (FIGO 0-5) patients should initially receive IM MTX/FA due to its low toxicity, outpatient administration and reasonable efficacy. Patients with FIGO score 6 or FIGO stage III disease should make an informed choice between IM MTX/FA and combination chemotherapy.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Coriocarcinoma/tratamento farmacológico , Doença Trofoblástica Gestacional/tratamento farmacológico , Metotrexato/uso terapêutico , Adulto , Coriocarcinoma/sangue , Gonadotropina Coriônica/sangue , Feminino , Doença Trofoblástica Gestacional/sangue , Humanos , Gravidez , Estudos Retrospectivos , Fatores de Risco , Reino Unido
19.
J Obstet Gynaecol ; 33(5): 479-83, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23815201

RESUMO

Extramammary Paget's disease (EMPD) is a rare intraepidermal adenocarcinoma that can affect the vulval skin. Surgical excision is the gold-standard treatment, however, recurrence rates are high and extensive excisions can produce long-lasting cosmetic and functional defects. We describe one of the largest case series to-date (n = 6) on the use of topical 5% imiquimod cream as a novel treatment option and discuss our experiences. With the addition of our six cases to the literature, there are now 29 documented cases of vulval EMPD treated with 5% imiquimod cream. Of these, 50% of primary disease cases and 73% of recurrent primary disease cases have achieved clinical resolution with 5% imiquimod therapy alone. These findings suggest that imiquimod provides a viable alternative to surgical excision for vulval EMPD. However, we acknowledge that this is a simple retrospective analysis and that treatment scheduling and follow-up needs investigation in a trial setting.


Assuntos
Aminoquinolinas/administração & dosagem , Antineoplásicos/administração & dosagem , Doença de Paget Extramamária/tratamento farmacológico , Neoplasias Vulvares/tratamento farmacológico , Administração Cutânea , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios/administração & dosagem , Clobetasol/administração & dosagem , Clobetasol/análogos & derivados , Feminino , Humanos , Imiquimode , Pessoa de Meia-Idade
20.
Eur J Cancer ; 49(15): 3184-90, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23870384

RESUMO

BACKGROUND: 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. PATIENTS AND METHODS: 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 15 mg 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. RESULTS: 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 >100,000 iu/l compared to an hCG level of <100,000 iu/l (84% versus 34% p ≤ 0.0001). All patients were eventually cured with chemotherapy or surgical salvage. CONCLUSIONS: Patients with low risk GTN that have a FIGO/WHO score of 6 or hCG level of >100,000 iu/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.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença Trofoblástica Gestacional/tratamento farmacológico , Administração Oral , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Feminino , Doença Trofoblástica Gestacional/patologia , Humanos , Injeções Intramusculares , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Gravidez , Estudos Retrospectivos , Resultado do Tratamento
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