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1.
Artigo em Inglês | MEDLINE | ID: mdl-37245506

RESUMO

BACKGROUND: Gestational trophoblastic disease comprises hydatidiform moles and a rare group of malignancies that derive from trophoblasts. Although there are typical morphological features that may distinguish hydatidiform moles from non-molar products of conception, such features are not always present, especially at early stages of pregnancy. Furthermore, mosaic/chimeric pregnancies and twin pregnancies make pathological diagnosis challenging while trophoblastic tumours can also pose diagnostic problems in terms of their gestational or non-gestational origin. OBJECTIVES: To show that ancillary genetic testing can be used to aid diagnosis and clinical management of GTD. METHODS: Each author identified cases where genetic testing, including short tandem repeat (STR) genotyping, ploidy analysis, next generation sequencing and immunostaining for p57, the product of the imprinted gene CDKN1C, facilitated accurate diagnosis and improved patient management. Representative cases were chosen to illustrate the value of ancillary genetic testing in different scenarios. OUTCOME: Genetic analysis of placental tissue can aid in determining the risk of developing gestational trophoblastic neoplasia, facilitating discrimination between low risk triploid (partial) and high risk androgenetic (complete) moles, discriminating between a hydatidiform mole twinned with a normal conceptus and a triploid conception and identification of androgenetic/biparental diploid mosaicism. STR genotyping of placental tissue and targeted gene sequencing of patients can identify women with an inherited predisposition to recurrent molar pregnancies. Genotyping can distinguish gestational from non-gestational trophoblastic tumours using tissue or circulating tumour DNA, and can also identify the causative pregnancy which is the key prognostic factor for placental site and epithelioid trophoblastic tumours. CONCLUSIONS AND OUTLOOK: STR genotyping and P57 immunostaining have been invaluable to the management of gestational trophoblastic disease in many situations. The use of next generation sequencing and of liquid biopsies are opening up new pathways for GTD diagnostics. Development of these techniques has the potential to identify novel biomarkers of GTD and further refine diagnosis.

2.
Gynecol Oncol ; 165(3): 420-427, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35483986

RESUMO

BACKGROUND: A combination of tumour size, differentiation grade and location may identify a group of vulvar squamous cell cancer (VSCC) patients with a very low risk of inguinal lymph node metastasis. We aim to examine these findings in a large national cohort of VSCC patients. MATERIALS AND METHODS: Population based prospective data on VSCC patients treated with vulvectomy and primary groin surgery was obtained from the Danish Gynaecological Cancer Database. Univariate chi-square and multivariate logistic regression analysis were used. Statistical tests were 2-sided. P-values of <0.05 were considered statistically significant. RESULTS: In all, 388 VSCC patients were identified. Of these 264 (63.3%) were node negative and 121 (36.7%) node positive. Increasing tumour size (diameter ≤ 2 cm vs. > 2 to 4 cm), grade (1 vs. 2-3) and location of tumour to clitoris were all associated with a significantly increased risk of inguinal lymph node metastasis OR 2.81(95% CI 1.52-5.20), OR 3.19 (95% CI 1.77-5.74) and OR 2.74 (95% CI 1.56-5.20), respectively. Previous vulvar disease was not associated with lymph node metastasis. No lymph node metastasis was demonstrated in patients with grade 1 tumours, tumour size less than 2 cm and located outside the clitoris area (n = 51). CONCLUSIONS: VSCC patients with grade 1 tumours, ≤ 2 cm and without clitoral involvement have a very low risk of inguinal lymph node metastasis. These patients may be spared inguinal lymph node staging to decrease operating time and peri- and postoperative morbidity in the future. However, studies validating our findings are needed.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Vulvares , Carcinoma de Células Escamosas/patologia , Feminino , Virilha/cirurgia , Humanos , Excisão de Linfonodo/efeitos adversos , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática/patologia , Estadiamento de Neoplasias , Estudos Prospectivos , Estudos Retrospectivos , Neoplasias Vulvares/patologia
3.
Gynecol Oncol ; 156(1): 124-130, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31711658

RESUMO

OBJECTIVE: The sentinel node (SN) procedure is adopted in selected patients with early-stage vulva cancer (VC) in Denmark. Due to the low incidence of VC, large population-based studies on the safety of SN outside multicenter clinical trials are lacking. The current study evaluated the risk of recurrence and survival in SN- negative VC patients. METHODS: Nationwide data was collected and registered prospectively in the Danish Gynecologic Cancer Database from January 2011 to July 2017. Patients with clinically stage IB-II unifocal vulva squamous cell carcinoma, tumor <4 cm and no clinically suspicious groin nodes or distant metastases, who underwent SN-procedure, were included. RESULTS: The SN-procedure was performed in 286 patients, of these 190 (66.4%) patients were SN-negative. Twenty-three of the 190 SN-negative patients (12.1%) had one or more recurrences during a median follow-up of 30 months (range 1-83). Four patients (2.1%) had an isolated groin recurrence identified from 5 to 17 months after primary surgery. Fourteen patients (7.4%) experienced a local recurrence in vulva, 1 patient (0.5%) had a recurrence in the vulva and the groin and 4 patients (2.1%) had distant recurrences. The 3-year overall (OS) and disease-specific survival (DSS) for SN-negative patients was 84% and 93%, respectively. The 3-year OS for patients with recurrent disease was 58%. CONCLUSIONS: This is the largest prospective nationwide study on SN-procedure in vulva cancer. The study confirms the safety of the SN-procedure in selected early-stage VC patients with a low isolated groin recurrence rate and a good DSS.


Assuntos
Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Biópsia de Linfonodo Sentinela/estatística & dados numéricos , Neoplasias Vulvares/mortalidade , Neoplasias Vulvares/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Dinamarca/epidemiologia , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Sistema de Registros , Linfonodo Sentinela/patologia , Biópsia de Linfonodo Sentinela/efeitos adversos , Biópsia de Linfonodo Sentinela/métodos
4.
Acta Oncol ; 55(2): 234-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26106854

RESUMO

BACKGROUND: Treatment of postmolar gestational trophoblastic neoplasia (GTN) is often stratified according to FIGO score using methotrexate (MTX) for low-risk patients and first-line multi-agent chemotherapy (e.g. EMA-CO) for high-risk patients. In contrast, oral MTX may be given as first-line therapy to all GTN patients regardless of risk group. The aim was to examine the efficacy of oral MTX and a response-adapted treatment policy, which has been used for three decades at Aarhus University Hospital (AUH). MATERIAL AND METHODS: Seventy-one consecutive postmolar GTN patients treated 1981-2011 were included. Data were obtained from medical records, using histopathology and human choriogonadotropin (hCG) to verify the diagnosis. All patients received oral MTX as first-line chemotherapy. Second- and third-line chemotherapy was given according to response. RESULTS: Sixty-four (90%) patients were retrospectively categorized as FIGO low-risk disease, whereas seven patients (10%) had high-risk disease. Complete response to first-line oral MTX chemotherapy was observed in 35/71 (49%) patients, while 62/71 (87%) had complete remission on MTX (first-line) and/or MTX plus dactinomycin (second-line), without the use of multi-agent therapy. Nine patients (13%) received third-line multi-agent chemotherapy, six low-risk (67%) and three high-risk (33%) patients. There were no recurrences and no patients died as a consequence of toxicity or disease. CONCLUSION: Fifty percent of all patients can be cured on oral MTX alone. By adding dactinomycin, about 90% are cured without use of multi-agent chemotherapy. The use of oral MTX as initial treatment can minimize the number of patients receiving multi-agent chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença Trofoblástica Gestacional/tratamento farmacológico , Metotrexato/administração & dosagem , Administração Oral , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Gonadotropina Coriônica/sangue , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Dactinomicina/administração & dosagem , Dactinomicina/uso terapêutico , Etoposídeo/administração & dosagem , Etoposídeo/uso terapêutico , Feminino , Seguimentos , Doença Trofoblástica Gestacional/patologia , Humanos , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Gravidez , Fatores de Risco , Resultado do Tratamento , Vincristina/administração & dosagem , Vincristina/uso terapêutico , Adulto Jovem
5.
Am J Obstet Gynecol ; 211(4): 370.e1-19, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24657790

RESUMO

OBJECTIVE: The purpose of this study was to analyze the correlation between the genetic constitution and the phenotype in triploid pregnancies. STUDY DESIGN: One hundred fifty-eight triploid pregnancies were identified in hospitals in Western Denmark from April 1986 to April 2010. Clinical data and karyotypes were collected retrospectively, and archived samples were retrieved. The parental origin of the genome, either double paternal contribution (PPM) or double maternal contribution (MMP) was determined by an analysis of methylation levels at imprinted sites. RESULTS: There were significantly more PPM than MMP cases (P < .01). In MMP cases, the possible karyotypes had similar frequencies, whereas, in PPM cases, 43% had the karyotype 69,XXX, 51% had the karyotype 69,XXY, and 6% had the karyotype 69,XYY. Molar phenotype was seen only in PPM cases. However, PPM cases with a nonmolar phenotype were also seen. For both parental genotypes, various fetal phenotypes were seen at autopsy. Levels of human chorionic gonadotropin in maternal serum were low in MMP cases and varying in PPM cases, some being as low as in the MMP cases. CONCLUSION: In a triploid pregnancy, suspicion of hydatidiform mole at ultrasound scanning, by macroscopic inspection of the evacuated tissue, at histology, or because of a high human chorionic gonadotropin in maternal serum level each predict the parental type PPM with a very high specificity. In contrast, the sensitivity of these observations was <100%.


Assuntos
Cariótipo Anormal , Fenótipo , Diagnóstico Pré-Natal , Triploidia , Biomarcadores/sangue , Gonadotropina Coriônica/sangue , Feminino , Genótipo , Humanos , Mola Hidatiforme/sangue , Mola Hidatiforme/diagnóstico , Mola Hidatiforme/genética , Cariotipagem , Gravidez , Estudos Retrospectivos , Neoplasias Uterinas/sangue , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/genética
6.
Hum Reprod ; 28(7): 2010-20, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23633551

RESUMO

STUDY QUESTION: How does tetraploidy develop in hydatidiform moles (HMs), and what is the frequency of the different origins? SUMMARY ANSWER: Most molar pregnancies with tetraploid cells appear to be produced by somatic endoreduplications, while a minority originate from a tetraploid zygote. The frequency of zygotic tetraploidy was estimated to be 0.7%. WHAT IS KNOWN ALREADY: The parental origin of the genome in tetraploid HMs has only been evaluated in a few cases, most showing three genome sets from the father (PPPM). Estimates of the proportion of HMs that are tetraploid vary between 2 and 28%. STUDY DESIGN, SIZE, DURATION: From 1986 to 2010, unfixed samples of clinically suspected molar pregnancies were forwarded to the Danish Mole Project. For this cohort study 442 samples fulfilled the following criteria for inclusion: macroscopic appearance of HM and ≥ 10 vesicular chorionic villi with a diameter of ≥ 1 mm. PARTICIPANTS/MATERIALS, SETTING, METHODS: Of 403 karyotyped samples, 21 cases disclosed ≥ 2 tetraploid metaphases. The 21 cases were scrutinized by karyotyping, flow cytometry (FC) and DNA-marker analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Among 20 HMs, 3 showed the genotype PPPM: one with the sex chromosomes XXYY and two with XXXY, indicating that they originated in tetraploid zygotes. In 14 androgenetic, one likely androgenetic and two mosaics, the tetraploid cells likely developed by endoreduplications of diploid cells. One case did not fulfil the histopathological criteria for HM. LIMITATIONS, REASONS FOR CAUTION: As an inclusion criterion was the macroscopic observation of vesicular chorionic villi, some non-molar hydropic placentas may have been included and some early moles may have been excluded. WIDER IMPLICATIONS OF THE FINDINGS: In future, studies to determine that an HM is tetraploid and discriminate cases of mosaicism and to deduce the origin of the tetraploidy must use the techniques of karyotyping, DNA-marker analysis and FC in combination.


Assuntos
Mola Hidatiforme/genética , Tetraploidia , Feminino , Citometria de Fluxo , Marcadores Genéticos , Genoma Humano , Genótipo , Humanos , Cariotipagem , Modelos Genéticos , Placenta/patologia , Gravidez
7.
Placenta ; 135: 7-15, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36889013

RESUMO

INTRODUCTION: Identifying hydatidiform moles (HMs) is crucial due to the risk of gestational trophoblastic neoplasia. When a HM is suspected on clinical findings, surgical termination is recommended. However, in a substantial fraction of the cases, the conceptus is actually a non-molar miscarriage. If distinction between molar and non-molar gestations could be obtained before termination, surgical intervention could be minimized. METHODS: Circulating gestational trophoblasts (cGTs) were isolated from blood from 15 consecutive women suspected of molar pregnancies in gestational week 6-13. The trophoblasts were individually sorted using fluorescence activated cell sorting. STR analysis targeting 24 loci was performed on DNA isolated from maternal and paternal leukocytes, chorionic villi, cGTs, and cfDNA. RESULTS: With a gestational age above 10 weeks, cGTs were isolated in 87% of the cases. Two androgenetic HMs, three triploid diandric HMs, and six conceptuses with diploid biparental genome were diagnosed using cGTs. The STR profiles in cGTs were identical to the profiles in DNA from chorionic villi. Eight of the 15 women suspected to have a HM prior to termination had a conceptus with a diploid biparental genome, and thus most likely a non-molar miscarriage. DISCUSSION: Genetic analysis of cGTs is superior to identify HMs, compared to analysis of cfDNA, as it is not hampered by the presence of maternal DNA. cGTs provide information about the full genome in single cells, facilitating estimation of ploidy. This may be a step towards differentiating HMs from non-HMs before termination.


Assuntos
Aborto Espontâneo , Doença Trofoblástica Gestacional , Mola Hidatiforme , Neoplasias Uterinas , Gravidez , Feminino , Humanos , Lactente , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/genética , Trofoblastos , Mola Hidatiforme/diagnóstico , Mola Hidatiforme/genética
8.
Cancers (Basel) ; 14(3)2022 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-35159119

RESUMO

Methotrexate (MTX) is frequently used as first-line treatment for low-risk gestational trophoblastic neoplasia (GTN). Intravenous and intramuscular (im) routes of administration are the most common methods, although oral administration is used by some Scandinavian centers. The primary aim of this study was to assess the impact of form of administration (im/oral) on resistance to methotrexate (MTX-R) treatment in low-risk GTN. Secondary aims were time to hCG normalization, rates of toxicity-induced treatment switch, and rates of complete remission and recurrence. In total, 170 women treated at Karolinska University Hospital in Sweden and Aarhus University Hospital in Denmark between 1994 and 2018 were included, of whom 107 were given im and 63 oral MTX. MTX-R developed in 35% and 54% in the im and oral groups, respectively (p = 0.01). There was no difference in days to hCG normalization (42 vs. 41 days, p = 0.50) for MTX-sensitive women. Toxicity-induced treatment switch was only seen in the im group. Complete remission was obtained in 99.1% and 100% (p = 0.44), and recurrence rate within one year was 2.8% and 1.6% (p = 0.29). The form of administration of MTX had a significant impact on development of MTX-R and treatment-associated toxicity, but does not affect rates of complete remission, recurrence or survival.

9.
Mol Genet Genomic Med ; 9(1): e1565, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33306861

RESUMO

BACKGROUND: In gestational trophoblastic disease, the prognosis is related to the genetic constitution. In some cases, taking a biopsy is contraindicated. METHODS: In a pregnant woman, ultrasound scanning suggested hydatidiform mole. To explore if the genetic constitution can be established without taking a biopsy (or terminating the pregnancy), cell-free DNA and circulating gestational trophoblasts were isolated from maternal blood before evacuation of the uterus. The evacuated tissue showed the morphology of a complete hydatidiform mole. Without prior whole-genome amplification, short tandem repeat analysis of 24 DNA markers was performed on the samples, and on DNA isolated from evacuated tissue, and from the blood of the patient and her partner. RESULTS: Identical genetic results were obtained in each of three circulating gestational trophoblasts and the evacuated tissue, showing that this conceptus had a diploid androgenetic nuclear genome. In contrast, analysis of cell-free DNA was less informative and less specific due to the inherent presence of cell-free DNA from the patient. CONCLUSION: Our results show that it is possible to isolate and analyze circulating gestational trophoblasts originating in a pregnancy without maternal nuclear genome. For diagnosing gestational trophoblastic diseases, genotyping circulating gestational trophoblasts appears to be superior to analysis of cell-free DNA.


Assuntos
Testes Genéticos/métodos , Mola Hidatiforme/genética , Células Neoplásicas Circulantes/metabolismo , Trofoblastos/metabolismo , Adulto , Células Cultivadas , Feminino , Humanos , Mola Hidatiforme/diagnóstico por imagem , Mola Hidatiforme/patologia , Células Neoplásicas Circulantes/patologia , Gravidez , Trofoblastos/patologia , Ultrassonografia Pré-Natal
10.
Ugeskr Laeger ; 181(34)2019 Aug 19.
Artigo em Da | MEDLINE | ID: mdl-31495360

RESUMO

This review summarises the current guidelines for vulva cancer in Denmark. Vulva cancer is a rare disease. The diagnosis is often delayed, which results in large tumours and regional spread. The most important prognostic factor is inguinal lymph node metastases. Staging and treatment is centralised to two hospitals. Primary treatment is wide local excision combined with removal of either inguinal sentinel nodes or lymphadenectomy. Treatment is associated with considerable morbidity, and supportive care is often necessary. Local curable recurrences are common. Relapses in the groin are associated with a poor prognosis. Thus, long term follow-up is essential. *) On behalf of Dansk Gynækologisk Cancer Gruppe for vulvacancer.


Assuntos
Neoplasias Vulvares , Dinamarca , Feminino , Seguimentos , Humanos , Excisão de Linfonodo , Linfonodos , Metástase Linfática , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Biópsia de Linfonodo Sentinela , Neoplasias Vulvares/diagnóstico , Neoplasias Vulvares/cirurgia
11.
Hum Reprod ; 23(9): 2031-5, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18556678

RESUMO

BACKGROUND: In twin pregnancies comprising a hydatidiform mole and a normal co-fetus, the ploidy of the mole is almost exclusively reported as diploid and very rarely as triploid. We aimed at understanding this unbalanced distribution of diploid and triploid moles in twin pregnancies by investigating the number of gametes involved. METHODS: Using polymorphic DNA markers, we compared the alleles of seven moles with those of the normal co-fetuses and deduced the number of oocytes and spermatozoa represented in each twin pregnancy. RESULTS: The genomes of all seven moles were androgenetic diploid; six moles were homozygous in all loci analyzed and one mole was heterozygous in several loci. In one homozygous mole, the paternal alleles were identical to those of the normal co-fetus in 13 non-linked informative microsatellite loci, indicating the involvement of one spermatozoon only, and thus of one oocyte only. Duplications of the paternal genome followed by abnormal cell division can explain this observation. In six moles, the paternal alleles were different from those of the normal co-fetus suggesting involvement of two (or more) spermatozoa. Overfertilization of one oocyte followed by abnormal cell division is a possibility. CONCLUSIONS: It is possible that twin pregnancies comprising a diploid mole and a normal co-fetus most often derive from one single oocyte fertilized with one or more spermatozoa. This can explain why diploid moles are far more frequent than triploid moles in twin pregnancies.


Assuntos
Diploide , Doenças em Gêmeos/genética , Mola Hidatiforme/genética , Neoplasias Uterinas/genética , Alelos , Doenças em Gêmeos/patologia , Feminino , Citometria de Fluxo , Ligação Genética , Genoma Humano , Humanos , Mola Hidatiforme/patologia , Hibridização in Situ Fluorescente , Cariotipagem , Masculino , Repetições de Microssatélites , Modelos Genéticos , Oócitos/crescimento & desenvolvimento , Oócitos/patologia , Polimorfismo Genético , Gravidez , Espermatozoides/patologia , Neoplasias Uterinas/patologia
12.
Am J Obstet Gynecol ; 197(1): 45.e1-5, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17618752

RESUMO

OBJECTIVE: This study was undertaken to evaluate the risk of persistent trophoblastic disease and obstetric complications related to a multiple pregnancy comprising a diploid hydatidiform mole and normal cofetus(es). STUDY DESIGN: From a database of 270 consecutively collected hydatidiform moles, 8 multiple and 154 singleton molar pregnancies were identified. Molar and fetal ploidy was determined, and data on clinical features and chemotherapy were collected. Differences between groups were assessed with Fisher's exact or Mann-Whitney test. RESULTS: The molar component in all 8 multiple pregnancies was diploid. Five patients with diploid mole and coexisting fetus pregnancy chose to terminate their pregnancy, 2 aborted spontaneously, and 1 patient delivered a healthy child. Two diploid mole and coexisting fetus pregnancies (25%) and 17% of the singleton molar pregnancies were followed by persistent trophoblastic disease (P = .63). CONCLUSION: The risk of persistent trophoblastic disease after a diploid mole with coexisting fetus pregnancy is similar to that after a singleton molar pregnancy, and expectant management instead of therapeutic abortion can be pursued.


Assuntos
Mola Hidatiforme/complicações , Complicações Neoplásicas na Gravidez , Gêmeos , Neoplasias Uterinas/complicações , Adulto , Diploide , Feminino , Idade Gestacional , Humanos , Gravidez , Estudos Retrospectivos , Fatores de Risco
13.
Obstet Gynecol ; 107(5): 1006-11, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16648403

RESUMO

OBJECTIVE: To search for predictive factors for low risk of persistent trophoblastic disease in patients with molar pregnancies. METHODS: A total of 270 consecutively collected, histologically confirmed hydatidiform moles were classified by ploidy using karyotyping and flow cytometry. The parental origin of the genome was determined by analysis of microsatellite polymorphisms. Data on clinical features and pathology reports were collected for each patient. RESULTS: The observed frequency of persistent trophoblastic disease in patients with triploid moles was 0 of 105, (95% confidence interval 0-2.8%), whereas 28 of 162 patients with diploid molar pregnancies developed persistent trophoblastic disease (P < .001). Patients with a diploid mole and an initial hCG level lower than 49,000 units per liter did not develop persistent trophoblastic disease (P = .03). CONCLUSION: The risk of persistent trophoblastic disease after a triploid mole is very low. By combining the present data with data from published studies with valid ploidy assessment, the frequency of persistent trophoblastic disease in patients with triploid moles is 0 of 196 (95% confidence interval 0-1.5%). We suggest that the surveillance program for patients with triploid molar pregnancies is shortened. Initial hCG less than 49,000 units per liter is a possible predictor of low risk of persistent trophoblastic disease in women with diploid molar pregnancies, but this observation needs confirmation in larger studies.


Assuntos
Mola Hidatiforme/etiologia , Regressão Neoplásica Espontânea , Neoplasias Uterinas/etiologia , Adulto , Gonadotropina Coriônica/sangue , Feminino , Genótipo , Humanos , Mola Hidatiforme/sangue , Mola Hidatiforme/patologia , Pessoa de Meia-Idade , Ploidias , Valor Preditivo dos Testes , Gravidez , Medição de Risco , Neoplasias Uterinas/sangue , Neoplasias Uterinas/patologia
14.
Medicine (Baltimore) ; 95(37): e4721, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27631219

RESUMO

BACKGROUND: This case report describes the use of analysis of cell-free DNA in the blood of a patient with a pregnancy with one live fetus and a choriocarcinoma diagnosed at 22 weeks of gestation. RESULTS: The result of the analysis of 16 microsatellite loci on 14 chromosomes in the cell-free DNA in plasma was consistent with the result of the analysis of a tumor biopsy indicating biparental diploid origin of the genome. The DNA markers were discordant with the markers of the placenta indicating two separate conceptions. CONCLUSION: Our results indicate that analysis of cell-free DNA in plasma allows determination of the origin of a choriocarcinoma without tissue biopsy, even in the presence of a co-existent pregnancy.


Assuntos
Coriocarcinoma/sangue , DNA/sangue , Adulto , Feminino , Humanos , Nascido Vivo , Gravidez
15.
Eur J Cancer ; 51(13): 1725-31, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26092638

RESUMO

Gestational trophoblastic disease (GTD) is a spectrum of cellular proliferations arising from trophoblast. Their invasive and metastatic potential sometimes requires chemotherapy and/or surgery. Current management is generally associated with favourable prognosis. Therefore, treatments must be chosen according to the desire for further childbearing of each patient. The European Organisation for Treatment of Trophoblastic Diseases (EOTTD) is dedicated to optimise diagnosis, treatment, follow-up and research in GTD by bringing together knowledge of clinicians and researchers from 29 countries working in the field of GTD in Europe. This study assessed the level of agreement among an expert panel of the EOTTD in order to rationalise the management of patients in Europe. The RAND/UCLA Appropriateness Method was used to combine the best available scientific evidence with the collective judgment of experts to yield a statement regarding the appropriateness of performing a procedure at the level of patient-specific symptoms, medical history and test results. There was an agreement for 54 statements while the experts showed a disagreement for two statements. As there is little evidence from randomised trials on which to base recommendations about management of GTD, many of these recommendations are based on expert opinion derived from changes in management fact that have improved outcomes from nearly 100% fatality to nearly 100% cure rates. However, a large agreement among experts is invaluable to the individual clinician who is struggling to decide whether a fertility-sparing treatment of hydatidiform mole or a low-risk GTN can be chosen and how it must be conducted.


Assuntos
Medicina Baseada em Evidências/normas , Doença Trofoblástica Gestacional/terapia , Oncologia/normas , Consenso , Comportamento Cooperativo , Técnica Delphi , Europa (Continente) , Feminino , Doença Trofoblástica Gestacional/diagnóstico , Humanos , Cooperação Internacional , Valor Preditivo dos Testes , Gravidez , Prognóstico
16.
PLoS One ; 10(11): e0142545, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26562155

RESUMO

Hydatidiform moles (HMs) are abnormal human pregnancies with vesicular chorionic villi, imposing two clinical challenges; miscarriage and a risk of gestational trophoblastic neoplasia (GTN). The parental type of most HMs are either diandric diploid (PP) or diandric triploid (PPM). We consecutively collected 154 triploid or near-triploid samples from conceptuses with vesicular chorionic villi. We used analysis of DNA markers and/or methylation sensitive-MLPA and collected data from registries and patients records. We performed whole genome SNP analysis of one case of twinning (PP+PM).In all 154 triploids or near-triploids we found two different paternal contributions to the genome (P1P2M). The ratios between the sex chromosomal constitutions XXX, XXY, and XYY were 5.7: 6.9: 1.0. No cases of GTN were observed. Our results corroborate that all triploid human conceptuses with vesicular chorionic villi have the parental type P1P2M. The sex chromosomal ratios suggest approximately equal frequencies of meiosis I and meiosis II errors with selection against the XYY conceptuses or a combination of dispermy, non-disjunction in meiosis I and meiosis II and selection against XYY conceptuses. Although single cases of GTN after a triploid HM have been reported, the results of this study combined with data from previous prospective studies estimate the risk of GTN after a triploid mole to 0% (95% CI: 0-1,4%).


Assuntos
Vilosidades Coriônicas/metabolismo , Mola Hidatiforme/genética , Aberrações dos Cromossomos Sexuais , Triploidia , Diploide , Feminino , Genoma Humano/genética , Genótipo , Humanos , Cariótipo , Cariotipagem , Masculino , Modelos Genéticos , Gravidez
17.
Dan Med J ; 62(11): A5082, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26522484

RESUMO

Hydatidiform mole is treated with surgical uterine evacuation with suction and blunt curettage (D). Medical uterine evacuation should not be used (C). On clinical suspicion of hydatidiform mole, one representative sample of the evacuated tissue is fixed for histopathologic investigation and one is forwarded unfixed for genetic analysis (D). Serum hCG is measured on suspicion of hydatidiform mole. At the time of the uterine evacuation, the initial hCG is measured (A). After a hydatidiform mole that is both triploid and partial, serum hCG is measured weekly until there are two consecutive undetectable values (< 1 or < 2), after which the patient can be discharged from follow-up (C). After a diploid hydatidiform mole, a complete mole, or a hydatidiform mole without valid ploidy determination, serum hCG is measured weekly until the value is undetectable (< 1 or < 2). If serum hCG is undetectable within 56 days after evacuation, the patient can be discharged from follow-up after an additional four monthly measurements. If serum hCG is first normalised after 56 days, the patient is follow-up with monthly serum hCG measurement for six months. Safe contraception should be used during the follow-up period (A). If hCG stagnates (less than 10% fall over three measurements), increases, or if hCG can be demonstrated for longer than 6 months, the patient by definition has persistent trophoblastic disease (PTD). A chest X-ray should be taken and a gynaecologic ultrasound scanning performed. The patient is referred to oncologic treatment (A). Uterine re-evacuation as a treatment for PTD can, in general, not be recommended because the rate of remission is low, and there is the risk of perforation of the uterus (C). In all following pregnancies, the woman is offered an early ultrasound scan, e.g. in gestational week eight (D). Eight weeks after termination of all future pregnancies, serum hCG is measured (D). In PTD and invasive hydatidiform mole, the primary treatment is MTX, either orally every third week or IV every week (B). In MTX-resistant PTD, IV act D is added (or replaces the MTX) (B). Third line chemotherapy is BEP or EP, alternatively EMA-CO (B). Choriocarcinoma is primarily treated with chemotherapy. Hysterectomy and/or resection of metastases are possible treatments (A). Placental site trophoblastic tumour (PSTT) and epithelioid trophoblastic tumour (ETT) are primarily treated with hysterectomy. In the case of disseminated disease, chemotherapy is considered (A). The risk of reoccurrence after trophoblastic disease treated with chemotherapy is approximately 3%. Most reoccurrences are seen within 12 months, and for this reason monitoring of hCG is recommended for one year, the first third months once or twice a month, thereafter every second to third month. Patients with PSTT and ETT are monitored with measurement of hCG throughout their lifetimes (C). In genetically verified twin pregnancy with hydatidiform mole and a living foetus, the pregnancy can continue if serum hCG is monitored and ultrasound scans regularly performed, and possible obstetric complications dealt with (C). In the case of recurrent hydatidiform mole and/or familial hydatidiform mole, patients should be referred to genetic workup and counselling (C). Women with a hereditary disposition to hydatidiform mole because of a mutation in NLRP7 should be informed of the possibility of becoming pregnant via egg donation (C).


Assuntos
Gonadotropina Coriônica/sangue , Doença Trofoblástica Gestacional/classificação , Doença Trofoblástica Gestacional/diagnóstico , Doença Trofoblástica Gestacional/terapia , Complicações Neoplásicas na Gravidez/terapia , Neoplasias Uterinas/terapia , Aconselhamento , Dinamarca , Feminino , Idade Gestacional , Humanos , Gravidez , Complicações Neoplásicas na Gravidez/diagnóstico , Fatores de Risco , Neoplasias Uterinas/diagnóstico
19.
Medicine (Baltimore) ; 94(44): e1776, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26554776

RESUMO

Hydatidiform mole is an abnormal human pregnancy characterized by the fetus being absent or nonviable, and the chorionic villi being vesicular and with trophoblastic hyperplasia. Most often, the mole phenotype is seen in conceptuses with an excess of paternally inherited genome set(s) relative to maternally inherited genome set(s), suggesting that the phenotype is caused by an excess of genome with a paternal imprinting pattern. However, it is unknown if correct parental origin of every imprinted gene is crucial for normal early differentiation or if abnormal parental imprinting of only one, or some, gene(s) can cause the mole phenotype.Two conceptuses included in the Danish Mole Project stood out since they presented with vesicular chorionic villi and without signs of fetal differentiation, and had apparently biparental diploid genomes, and no mutations in NLRP7 or KHDC3L were detected in the mothers. These conceptuses were subjected to a centralized histopathological revision and their genetic complements were scrutinized using fluorescence in situ hybridization, and DNA-marker and array comparative genomic hybridization analyses. Both conceptuses showed dysmorphic chorionic villi with some similarities to hydatidiform moles; however, no definite florid trophoblast hyperplasia was observed. Both conceptuses showed paternal hemizygosity of 11pter-11p15.4, most likely in nonmosaic state.Our findings suggest that the product of one (or a few) maternally expressed gene(s) on the tip of chromosome 11 is necessary for normal early embryonic differentiation. However, since the present two cases did not exhibit all features of hydatidiform moles, it is likely that abnormal parental imprinting of genes in other regions contribute to the phenotype of a hydatidiform mole.


Assuntos
DNA de Neoplasias/genética , Mola Hidatiforme/genética , Neoplasias Uterinas/genética , Hibridização Genômica Comparativa , Feminino , Impressão Genômica , Genótipo , Humanos , Hibridização in Situ Fluorescente , Fenótipo , Gravidez , Estudos Retrospectivos
20.
Ugeskr Laeger ; 165(11): 1130-2, 2003 Mar 10.
Artigo em Da | MEDLINE | ID: mdl-12677990

RESUMO

INTRODUCTION: The aim of this study was to examine how often information about the best way of giving birth after a primary caesarean section was given and to describe the frequency of repeated caesarean section. MATERIAL AND METHODS: Notifications of 108 women with primary caesarean section in the three-year period 1994-1996. RESULTS: Documentated information was given to 41%. A total of 43% had a repeated caesarean section, most frequently seen in the dystocia group (80%) as compared to the breech group (15%), which shows a significant difference, p < 0.01. CONCLUSION: This study shows that less than half of the women had been informed about future delivery following a primary caesarean section. The rate of repeated caesarean sections varies with the indication of the primary caesarean. Improved information is suggested in order to avoid that women desist from further pregnancies because of uncertainty.


Assuntos
Recesariana , Cesárea , Nascimento Vaginal Após Cesárea , Cesárea/efeitos adversos , Recesariana/estatística & dados numéricos , Serviços de Planejamento Familiar , Feminino , Humanos , Educação de Pacientes como Assunto/normas , Gravidez , Estudos Retrospectivos
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