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Thesis (MMed)--Stellenbosch University, 2012. / ENGLISH ABSTRACT: Objective: The aim of the study was to determine whether Beta-hCG levels at various time intervals during the follow-up period after primary treatment of molar pregnancies could be used to predict progression of the disease later, in an attempt to shorten the period of surveillance. Furthermore an assessment of the demographic details and risk factors for the development of persistent trophoblastic disease was examined. Levels of compliance to the current surveillance protocol were evaluated. Method: A retrospective analysis of all patients diagnosed with molar pregnancies at Tygerberg Hospital, Cape Town from January 2000 to December 2010. Results: Among the 120 patients, 13 (19.7%) of complete moles and 10 (20%) of partial moles developed persistent trophoblastic disease. There was no statistical significance of the demographic data when comparing the two types of moles. 66% of complete and 50% of partial moles were lost to follow-up within the first six months of surveillance. A potential Beta-hCG cut-off value of 148mIU/ml at week 6 offered a sensitivity of 0.89 and specificity of 0.88 that surveillance could be terminated. Conclusions: Patient compliance is a limiting factor in the evaluation of molar pregnancy surveillance. However, based on our results, the suggestion that termination of surveillance after primary evacuation could occur at 6 weeks if the Beta-hCG level was 148 mIU/ml or lower remains undecided, and it is our opinion that higher sensitivities and specificities are required. Further research is needed to solidify this claim. The acquisition of demographic information of our population remains a priority, in order for more informed decisions to be made. / AFRIKAANSE OPSOMMING: Doel: Die doel van die studie was om te bepaal of Beta-mCG vlakke of verskillende intervalle, gedurende die opvolg periode na primêre behandeling van mola swangerskappe gebruik kan word om siekte progressie te voorspel, en sodoende die tydperk van opvolg te verminder. Verder was die demografiese besonderhede en risiko faktore vir die ontwikkeling van persisterende trofoblastiese siekte ondersoek. Die nakoming tot die huidige toesighouding protokol was geevalueer. Metode: ‘n Retrospektiewe analise van al die pasiënte wat gediagnoseer is met ‘n mola swangerskap by Tygerberg Hospitaal, Kaapstad vanaf Januarie 2000 tot Desember 2010. Resultate: Van die 120 pasiënte het 13 (19.7%) van die volledige molas en 10 (20%) van die gedeeltelike molas persisterende trofoblastiese siekte ontwikkel. Daar was geen statistiese belang in die demografiese data, wanneer die twee tipe molas met mekaar vergelyk is nie. 66% van die volledige en 50% van die gedeeltelike molas was verlore met opvolg binne die eerste ses maande van opvolg. ‘n Potensiële Beta-mCG afsnywaarde van 148mIU/ml op ses weke het ‘n sensitiwiteit van 0.89 en spesifisiteit van 0.88 gewys dat toesighouding getermineer kan word. Opsomming: Pasiënt nakoming is ‘n beperkende faktor in die opvolg van mola swangerskappe. Alhoewel, gebaseer op ons resultate, ons kan voorstel dat terminasie van “surveillance/toesighouding” na primêre lediging, kan plaasvind op 6 weke indien die Beta-mCG vlak 148mIU/ml of minder is, bly dit onbeslis. Dit is ons opinie dat hoër vlakke van sensitiwiteit en spesifisiteit nodig is. Verdere navorsing is nodig om hierdie voorstelling te staaf. Die invordering van demografiese inligting van ons populasie bly ‘n prioriteit, om sodoende meer ingeligte besluite te neem.

Preeclampsia and molar pregnancy are two devastating placental pathologies characterized by an immature proliferative trophoblast phenotype accompanied by excessive cell death. It is therefore of paramount importance to study the regulation of cell fate in the placenta, to gain a further understanding of the mechanisms that contribute to these diseases. In this dissertation we report that during normal placental development and in preeclampsia, Matador (Mtd), a pro-apoptotic member of the Bcl-2 family, has a dual function in regulating trophoblast cell proliferation and death. Importantly, we reveal a novel role of Mtd-L in promoting cyclin E1 expression and cell cycle progression. Of clinical importance, we also identify that both cyclin E1 and the CDK inhibitor p27, are increased in severe early onset preeclampsia. However, the inhibitory function of p27 in this pathology may be hampered due to its increased phosphorylation at Ser10, resulting in its nuclear export. Of equal importance, data presented demonstrate that placentae from severe early onset preeclampsia display a molecular profile distinct from late onset preeclampsia or intrauterine growth restricted pregnancies. In the final data chapter we demonstrate that Mtd is highly expressed in molar tissue, where it localizes to both apoptotic and proliferative cells. Our data suggests that an abundance of Mtd and cyclin E1 in conjunction with the low level of p27 may contribute to the hyperproliferative nature of the disorder. The body of work in this dissertation uncovers novel insights into the regulation of trophoblast cell fate. Importantly, the impact of Mtd on cyclin E1 to promote G1-S transition is a novel mechanism found to regulate trophoblast cell proliferation in normal and pathological placentation. Equally important is our identification of molecular differences between placental pathologies that may help to differentiate early and late onset preeclampsia, IUGR and molar pregnancy.

Preeclampsia and molar pregnancy are two devastating placental pathologies characterized by an immature proliferative trophoblast phenotype accompanied by excessive cell death. It is therefore of paramount importance to study the regulation of cell fate in the placenta, to gain a further understanding of the mechanisms that contribute to these diseases. In this dissertation we report that during normal placental development and in preeclampsia, Matador (Mtd), a pro-apoptotic member of the Bcl-2 family, has a dual function in regulating trophoblast cell proliferation and death. Importantly, we reveal a novel role of Mtd-L in promoting cyclin E1 expression and cell cycle progression. Of clinical importance, we also identify that both cyclin E1 and the CDK inhibitor p27, are increased in severe early onset preeclampsia. However, the inhibitory function of p27 in this pathology may be hampered due to its increased phosphorylation at Ser10, resulting in its nuclear export. Of equal importance, data presented demonstrate that placentae from severe early onset preeclampsia display a molecular profile distinct from late onset preeclampsia or intrauterine growth restricted pregnancies. In the final data chapter we demonstrate that Mtd is highly expressed in molar tissue, where it localizes to both apoptotic and proliferative cells. Our data suggests that an abundance of Mtd and cyclin E1 in conjunction with the low level of p27 may contribute to the hyperproliferative nature of the disorder. The body of work in this dissertation uncovers novel insights into the regulation of trophoblast cell fate. Importantly, the impact of Mtd on cyclin E1 to promote G1-S transition is a novel mechanism found to regulate trophoblast cell proliferation in normal and pathological placentation. Equally important is our identification of molecular differences between placental pathologies that may help to differentiate early and late onset preeclampsia, IUGR and molar pregnancy.

Orientador: Izildinha Maestá / Resumo: Objetivo. Avaliar a influência da contracepção hormonal (HC) no desenvolvimento da agressividade clínica da neoplasia trofoblástica gestacional (NTG) e no tempo para normalização da gonadotrofina coriônica humana (hCG). Desenho do estudo. Coorte retrospectiva. Local do estudo. Centro de Doença Trofoblástica Gestacional do Rio de Janeiro. Pacientes. Pacientes diagnosticadas com gravidez molar. Intervenção. Comparação entre mulheres usuárias de HC ou métodos de barreira (BM) durante todo o acompanhamento da GTD. Desfecho primário. Ocorrência de GTN pós-molar e intervalo para a normalização dos níveis de hCG. Resultados. O uso de HC não influenciou a ocorrência de GTN pós-molar (Odds ratio ajustada - ORa: 0.66, 95% CI: 0.24-1,12, p=0.060), a despeito do tipo de HC utilizada: progesterona isolada (ORa: 0,54, 95% CI: 0.29-1,01, p=0.060) ou contracepção hormonal oral combinada (COC) (ORa: 0.50, 95% CI: 0.27-1.01, p=0.060) ou com diferentes dosagens etinilestradiol, 15mcg (ORa: 1,33, 95% CI: 0.79-2,24, p=0.288), 20mcg (ORa: 1.02, 95% CI: 0.64-1.65, p=0.901), 30mcg (ORa: 1.17, 95%CI: 0.78-1,75, p=0.437) ou 35mcg (ORa: 0.77, 95%CI: 0.42-1,39, p=0.386).O tempo para normalização de hCG ≥ 10 semanas (ORa: 0.58, 95% CI: 0.43-1.08, p=0.071) ou tempo de remissão após quimioterapia ≥ 14 semanas (ORa: 0.60, 95% CI: 0.43-1.09, p=0.067) não diferiram significativamente entre os usuários de HC quando comparadas aos pacientes que utilizam BM, ao controlar outros fatores de risco usando regressão ... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Objective. To evaluate the influence of hormonal contraception (HC) on the development and clinical aggressiveness of gestational trophoblastic neoplasia (GTN) and the time for normalization of human chorionic gonadotrophin (hCG) levels. Study design. Retrospective cohort. Setting. Rio de Janeiro Trophoblastic Disease Center. Patient(s). Women diagnosed with molar pregnancy. Intervention(s). Comparison between users of HC or barrier methods (BM) during the postmolar follow-up or postmolar GTN treatment. Main Outcome Measure(s). Occurrence of post-molar GTN and the time for hCG levels normalization. Result(s). The use of HC did not significantly influence the occurrence of postmolar GTN (ORa: 0.66, 95% CI: 0.24-1.12, p=0.060), despite different formulations: progesteroneonly (ORa: 0.54, 95% CI: 0.29-1.01, p=0.060) or combined oral contraception (COC) (ORa: 0.50, 95% CI: 0.27-1.01, p=0.60) or with different dosages of ethinyl estradiol: 15 mcg (ORa, 1.33, 95% CI 0.79-2.24, p=0.288), 20 mcg (ORa: 1.02, 95% CI: 0.64-1.65, p=0.901), 30 mcg (ORa: 1.17, 95% CI: 0.78-1.75, p=0.437) or 35 mcg (ORa: 0.77, 95% CI: 0.42-1.39, p=0.386). The time to hCG normalization ≥ 10 weeks (ORa: 0.58, 95% CI: 0.43-1.08, p=0.071) or the time to remission after chemotherapy ≥ 14 weeks (ORa: 0.60, 95% CI: 0.43-1.09, p=0.067) did not significantly differ among HC users when compared to patients using BM, when controlling for other risk factors using multivariate logistic regression. Conclusion(s). The use... (Complete abstract click electronic access below) / Doutor

Orientador: Izildinha Maestá / Coorientador: Marilza Vieira Cunha Rudge / Coorientador: Rafael Cortés-Charry / Banca: Antônio Rodrigues Braga Neto / Banca: Jurandyr Moreira de Andrade / Resumo: Avaliar o prognóstico da mola hidatiforme (MH) e tratamento da neoplasia trofoblástica gestacional (NTG) pós-molar acompanhadas no Centro de Referência para Doenças Trofoblásticas (CDT) versus outras instituições (OI). Estudo de coorte que incluiu 270 pacientes com MH (204 pacientes acompanhas do CDT-Botucatu, onde essa investigação está sendo realizada, e 66 pacientes inicialmente acompanhadas em OI). Todas as pacientes foram registradas no banco de dados do CDT-Botucatu (Universidade Estadual Paulista, Brasil) entre janeiro de 1990 e dezembro de 2009. O prognóstico da MH, bem como as características da NTG e seu desfecho foram analisados e comparados de acordo com o local de seguimento pós-molar. As seguintes variáveis de confundimento foram incluídas: idade (anos), número de gestação, paridade, número de abortamentos, e o tipo de MH (Completa/Parcial). O desfecho da NTG pós-molar consoante o local de seguimento pós-molar foi comparado utilizando-se o teste de Mann-Whitney, teste do Qui-Quadrado ou teste Exato de Fisher. NTG pós-molar ocorreu em 34 (34/204=16,7%) das pacientes que foram acompanhadas no CDT, e em 27 (27/66=40,9%) daquelas que realizaram o seguimento em OI. Pacientes que foram seguidas no CDT cursaram com características de NTG com melhor prognóstico, tais como: menor índice de metástases (5,8% versus 48%,p=0,003), menor mediana do escore FIGO 2000 [2,00 (1,00; 3,00) versus 4,00 (2,00; 7,00), p=0,003] e início mais precoce da quimioterapia em semanas [7,0 (6,0; 10,0) versus 10,0 (7,0; 16,0), p=0,04]. NTG de alto-risco não foi observada em nenhuma paciente submetida ao EUCDT, ocorrendo em 29% daquelas que foram acompanhadas em OI (p<0,001). Quimioterapia com múltiplos agentes para o tratamento da NTG pós-molar foi necessária em dois casos... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: To review treatment results of gestational trophoblastic neoplasia (GTN) after hydatidiform mole (HM) evacuation at a referral center (ERC) versus HM evacuation at other institutions (EOI). This cohort study included 270 patients undergoing HM evacuation (204 at the study referral center and 66 at other institutions). All patients were registered in the database of Botucatu Trophoblastic Diseases Center (São Paulo State University, Brazil) between January 1990 and December 2009. GTN characteristics and outcomes were analyzed and compared according to HM evacuation setting. The confounding variables assessed included age (years), number of gestations, parity, number of abortions, and HM type (Complete/Partial). Post-molar GTN outcomes according to HM evacuation setting were compared using Mann-Whitney's test, Chi-square test, or Fisher's exact test. Post-molar GTN occurred in 34 (34/204=16.7%) patients undergoing HM evacuation at the referral center, and in 27 (27/66=40.9%) of those undergoing HM evacuation in other institutions. Patients undergoing HM ERC showed GTN characteristics indicative of better prognosis such as: lower metastasis rate (5.8% versus 48%, p=0.003), lower median FIGO 2000 score [2.00 (1.00; 3.00) versus 4.00 (2.00; 7.00), p=0.003], and earlier chemotherapy onset in weeks [7.0 (6.0; 10.0) versus 10.0 (7.0; 16.0), p=0.04]. High-risk post-molar GTN was observed in no patient undergoing HM ERC, and in 29% of those undergoing HM EOI (p<0.001). Multi-agent chemotherapy for the treatment of post-molar GTN was required in two cases of HM evacuation at the referral center (5.9%) and in eight cases of HM EOI (29.6%) (p=0.017). Median time interval between chemotherapy onset and hCG. normalization in weeks was shorter among patients undergoing HM ERC [9.00 (6.25; 12.0) versus... (Complete abstract click electronic access below) / Mestre

Submitted by RENAN ROCHA SOARES null (rrsoaresmed@bol.com.br) on 2016-04-27T16:57:55Z No. of bitstreams: 1 Tese Doutorado Renan Soares.pdf: 1390332 bytes, checksum: 5a3cf50c9899dc57629c6f4a978b7127 (MD5) / Approved for entry into archive by Felipe Augusto Arakaki (arakaki@reitoria.unesp.br) on 2016-04-29T21:00:38Z (GMT) No. of bitstreams: 1 soares_rr_dr_bot.pdf: 1390332 bytes, checksum: 5a3cf50c9899dc57629c6f4a978b7127 (MD5) / Made available in DSpace on 2016-04-29T21:00:38Z (GMT). No. of bitstreams: 1 soares_rr_dr_bot.pdf: 1390332 bytes, checksum: 5a3cf50c9899dc57629c6f4a978b7127 (MD5) Previous issue date: 2016-02-29 / Apesar de 10 a 34% das pacientes com gravidez molar serem adolescentes, a influencia da idade precoce na apresentação clínica e no risco de desenvolvimento de neoplasia trofoblástica gestacional pós-molar (GTN) ainda é incerto. Objetivos. Comparar a apresentação clínica da mola hidatiforme completa (MHC) e os fatores de risco associados com o desenvolvimento de NTG entre adolescentes da América do Norte e América do Sul. Métodos. Estudo de coorte não concorrente incluindo adolescentes (< 20 anos) com MHC tratadas em centro da América do Norte (New England Trophoblastic Disease Center, Universidade de Harvard, Estados Unidos) entre 1973-2009, e centros da América do Sul (Centro de Doença Trofoblástica de Botucatu – Universidade Estadual Paulista, Unesp, Brazil; Unidade Trofoblástica da Universidade Central da Venezuela e Maternidad Concepción Palácios de Caracas, Venezuela), entre 1990-2009. Dados clínicos das pacientes coletados foram idade, idade gestacional ao diagnóstico, tamanho do útero, hCG pré-esvaziamento, presença de cistos tecaluteínicos, anemia, sangramento vaginal, pré-eclampsia e hiperemese. As participantes do estudo foram alocadas em dois grupos de adolescentes: América do Norte (AN, n = 195) e América do Sul (AS, n = 231). Resultados. Na apresentação, anemia (AS = 48% vs AN = 15%; p <0,001), hiperemese (AS = 14% vs AN = 6%; p = 0,003), e hCG sérico elevado (AS = 229591 mUI / mL vs AN = 14000 mUI / mL; p <0,001) foram mais frequentes na AS que AN. Na AS, pré-eclâmpsia [AS: OR = 4,33 (1,37-13,65) vs AN: OR = 0,34 (0,04-2,86)], tamanho do útero> idade gestacional [AS: OR = 2,50 (1,26-4,94) vs AN: OR = 1,69 ( 0,87-3,26)]; e cistos> 6 cm [AS: OR = 2,25 (0,80-6,33) vs AN: OR = 1,43 (0,57-3,56)] tiveram maior impacto sobre o risco de desenvolver NTG pós-molar. Em contraste, apenas sangramento vaginal. [AS: OR = 1,37 (0,64-2,91) vs AN: OR = 2,79 (1,10-7, 06] influenciou risco de NTG na AN. Conclusões. Comparado à AN, MHC em adolescentes da AS mostraram complicações médicas mais frequentemente e fatores clínicos com maior impacto sobre o risco de desenvolvimento de NTG. / Although 10-34% of patients with molar pregnancy are adolescent, the influence of young age on the clinical presentation and risk of developing post-molar gestational trophoblastic neoplasia (GTN) is still unclear. Objectives. To compare complete hydatidiform mole (CHM) clinical presentation and risk factors associated with developing GTN between North American adolescents and South American counterparts. Methods. Non-concurrent cohort study including adolescents ( 20 years) with CHM referred to centers in North America (New England Trophoblastic Disease Center, Harvard University,USA) between 1973-2009, and South America (Botucatu Trophoblastic Disease Center-São Paulo State University-Unesp, Brazil; Trophoblastic Unit of Central University of Venezuela and Maternidad Concepcion Palacios of Caracas, Venezuela) between 1990-2009. Patient clinical data collected included age, gestational age at diagnosis, uterine size, pre-evacuation hCG, presence of theca lutein cysts, anemia, vaginal bleeding, preeclampsia, and hyperemesis. Study participants were allocated into two groups of adolescents: North American (NA,n=195) and South American (SA,n=231). Results. At presentation, anemia (SA=48% vs NA=15%;p<0.001), hyperemesis (SA=14% vs NA=6%;p=0.003), and elevated serum hCG (SA=229591 mUI/mL vs NA=14000 mUI/mL ; p<0.001) were more frequent in SA than in NA. In SA, preeclampsia (SA:OR=4.33(1.37-13.65) vs NA:OR=0.34(0.04- 2.86), uterine size>gestational age (SA:OR= 2.50(1.26-4.94) vs NA: OR=1.69(0.87- 3.26); and cysts > 6cm (SA: OR= 2.25(0.80-6.33) vs NA:OR=1.43(0.57-3.56) had greater impact on the risk of developing post-molar GTN. In contrast, only vaginal bleeding (SA:OR=1.37(0.64-2.91) vs NA: OR=2.79(1,10-7, 06) influenced GTN risk in NA. Conclusions. Compared to NA, CHM among SA adolescents showed medical complications more frequently, and clinical features with greater impact on risk of GTN development.

Submitted by PATRÍCIA RANGEL SOBRAL DANTAS null (patriciarsdantas@ig.com.br) on 2017-07-05T02:29:15Z No. of bitstreams: 1 TESE PRONTA em PDF.pdf: 809121 bytes, checksum: d03376387368a0bc2d16a2649bba87f0 (MD5) / Rejected by LUIZA DE MENEZES ROMANETTO (luizamenezes@reitoria.unesp.br), reason: Solicitamos que realize uma nova submissão seguindo as orientações abaixo: O título informado na folha de rosto do documento está diferente da capa e ficha catalográfica. Corrija esta informação no arquivo PDF e realize uma nova submissão contendo o arquivo correto. Agradecemos a compreensão. on 2017-07-11T19:01:44Z (GMT) / Submitted by PATRÍCIA RANGEL SOBRAL DANTAS Rangel Sobral dantas (patriciarsdantas@ig.com.br) on 2017-07-12T00:14:12Z No. of bitstreams: 1 TESE PRONTA (1) PDF CORRETA.pdf: 812835 bytes, checksum: 4b12a2f077a74d04c2b9f2e57b211263 (MD5) / Approved for entry into archive by LUIZA DE MENEZES ROMANETTO (luizamenezes@reitoria.unesp.br) on 2017-07-13T20:56:23Z (GMT) No. of bitstreams: 1 dantas_prs_dr_bot.pdf: 812835 bytes, checksum: 4b12a2f077a74d04c2b9f2e57b211263 (MD5) / Made available in DSpace on 2017-07-13T20:56:23Z (GMT). No. of bitstreams: 1 dantas_prs_dr_bot.pdf: 812835 bytes, checksum: 4b12a2f077a74d04c2b9f2e57b211263 (MD5) Previous issue date: 2017-05-29 / Objetivo. Avaliar a influência da contracepção hormonal (HC) no desenvolvimento da agressividade clínica da neoplasia trofoblástica gestacional (NTG) e no tempo para normalização da gonadotrofina coriônica humana (hCG). Desenho do estudo. Coorte retrospectiva. Local do estudo. Centro de Doença Trofoblástica Gestacional do Rio de Janeiro. Pacientes. Pacientes diagnosticadas com gravidez molar. Intervenção. Comparação entre mulheres usuárias de HC ou métodos de barreira (BM) durante todo o acompanhamento da GTD. Desfecho primário. Ocorrência de GTN pós-molar e intervalo para a normalização dos níveis de hCG. Resultados. O uso de HC não influenciou a ocorrência de GTN pós-molar (Odds ratio ajustada - ORa: 0.66, 95% CI: 0.24-1,12, p=0.060), a despeito do tipo de HC utilizada: progesterona isolada (ORa: 0,54, 95% CI: 0.29-1,01, p=0.060) ou contracepção hormonal oral combinada (COC) (ORa: 0.50, 95% CI: 0.27-1.01, p=0.060) ou com diferentes dosagens etinilestradiol, 15mcg (ORa: 1,33, 95% CI: 0.79-2,24, p=0.288), 20mcg (ORa: 1.02, 95% CI: 0.64-1.65, p=0.901), 30mcg (ORa: 1.17, 95%CI: 0.78-1,75, p=0.437) ou 35mcg (ORa: 0.77, 95%CI: 0.42-1,39, p=0.386).O tempo para normalização de hCG ≥ 10 semanas (ORa: 0.58, 95% CI: 0.43-1.08, p=0.071) ou tempo de remissão após quimioterapia ≥ 14 semanas (ORa: 0.60, 95% CI: 0.43-1.09, p=0.067) não diferiram significativamente entre os usuários de HC quando comparadas aos pacientes que utilizam BM, ao controlar outros fatores de risco usando regressão logística multivariada. O tempo de remissão após quimioterapia 14 semanasAdemais, foi significativamente menor o tempo para a remissão espontânea entre as usuárias de HC (9,3 versus 10,4 semanas, p<0,001), quando comparada às pacientes usuárias de BM, respectivamente. Conclusão. O uso de HC durante o seguimento pós-molar ou o tratamento pós-molar de NTG não parece aumentar o risco de NTG e não adiar a normalização dos níveis de hCG. / Objective. To evaluate the influence of hormonal contraception (HC) on the development and clinical aggressiveness of gestational trophoblastic neoplasia (GTN) and the time for normalization of human chorionic gonadotrophin (hCG) levels. Study design. Retrospective cohort. Setting. Rio de Janeiro Trophoblastic Disease Center. Patient(s). Women diagnosed with molar pregnancy. Intervention(s). Comparison between users of HC or barrier methods (BM) during the postmolar follow-up or postmolar GTN treatment. Main Outcome Measure(s). Occurrence of post-molar GTN and the time for hCG levels normalization. Result(s). The use of HC did not significantly influence the occurrence of postmolar GTN (ORa: 0.66, 95% CI: 0.24-1.12, p=0.060), despite different formulations: progesteroneonly (ORa: 0.54, 95% CI: 0.29-1.01, p=0.060) or combined oral contraception (COC) (ORa: 0.50, 95% CI: 0.27-1.01, p=0.60) or with different dosages of ethinyl estradiol: 15 mcg (ORa, 1.33, 95% CI 0.79-2.24, p=0.288), 20 mcg (ORa: 1.02, 95% CI: 0.64-1.65, p=0.901), 30 mcg (ORa: 1.17, 95% CI: 0.78-1.75, p=0.437) or 35 mcg (ORa: 0.77, 95% CI: 0.42-1.39, p=0.386). The time to hCG normalization ≥ 10 weeks (ORa: 0.58, 95% CI: 0.43-1.08, p=0.071) or the time to remission after chemotherapy ≥ 14 weeks (ORa: 0.60, 95% CI: 0.43-1.09, p=0.067) did not significantly differ among HC users when compared to patients using BM, when controlling for other risk factors using multivariate logistic regression. Conclusion(s). The use of HC during postmolar follow-up or postmolar GTN treatment does not seen to increase the risk of GTN and does not postpone normalization of hCG levels.

Orientador: Izildinha Maestá / Resumo: Apesar de 10 a 34% das pacientes com gravidez molar serem adolescentes,a influencia da idade precoce na apresentação clínica e no risco de desenvolvimento deneoplasia trofoblástica gestacional pós-molar (GTN) ainda é incerto. Objetivos.Comparar a apresentação clínica da mola hidatiforme completa (MHC) e os fatores derisco associados com o desenvolvimento de NTG entre adolescentes da América doNorte e América do Sul. Métodos. Estudo de coorte não concorrente incluindoadolescentes (< 20 anos) com MHC tratadas em centro da América do Norte (NewEngland Trophoblastic Disease Center, Universidade de Harvard, Estados Unidos) entre1973-2009, e centros da América do Sul (Centro de Doença Trofoblástica de Botucatu –Universidade Estadual Paulista, Unesp, Brazil; Unidade Trofoblástica da UniversidadeCentral da Venezuela e Maternidad Concepción Palácios de Caracas, Venezuela), entre1990-2009. Dados clínicos das pacientes coletados foram idade, idade gestacional aodiagnóstico, tamanho do útero, hCG pré-esvaziamento, presença de cistostecaluteínicos, anemia, sangramento vaginal, pré-eclampsia e hiperemese. Asparticipantes do estudo foram alocadas em dois grupos de adolescentes: América doNorte (AN, n = 195) e América do Sul (AS, n = 231). Resultados. Na apresentação,anemia (AS = 48% vs AN = 15%; p <0,001), hiperemese (AS = 14% vs AN = 6%; p =0,003), e hCG sérico elevado (AS = 229591 mUI / mL vs AN = 14000 mUI / mL; p<0,001) foram mais frequentes na AS que... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Although 10-34% of patients with molar pregnancy are adolescent, theinfluence of young age on the clinical presentation and risk of developing post-molargestational trophoblastic neoplasia (GTN) is still unclear. Objectives. To comparecomplete hydatidiform mole (CHM) clinical presentation and risk factors associatedwith developing GTN between North American adolescents and South Americancounterparts. Methods. Non-concurrent cohort study including adolescents ( 20 years)with CHM referred to centers in North America (New England Trophoblastic DiseaseCenter, Harvard University,USA) between 1973-2009, and South America (BotucatuTrophoblastic Disease Center-São Paulo State University-Unesp, Brazil; TrophoblasticUnit of Central University of Venezuela and Maternidad Concepcion Palacios ofCaracas, Venezuela) between 1990-2009. Patient clinical data collected included age,gestational age at diagnosis, uterine size, pre-evacuation hCG, presence of theca luteincysts, anemia, vaginal bleeding, preeclampsia, and hyperemesis. Study participants wereallocated into two groups of adolescents: North American (NA,n=195) and SouthAmerican (SA,n=231). Results. At presentation, anemia (SA=48% vsNA=15%;p<0.001), hyperemesis (SA=14% vs NA=6%;p=0.003), and elevated serumhCG (SA=229591 mUI/mL vs NA=14000 mUI/mL ; p<0.001) were more frequent inSA than in NA. In SA, preeclampsia (SA:OR=4.33(1.37-13.65) vs NA:OR=0.34(0.04-2.86), uterine size>gestational age (SA:OR= 2... (Complete abstract click electronic access below) / Doutor

Made available in DSpace on 2014-06-11T19:29:51Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-02-27Bitstream added on 2014-06-13T21:00:19Z : No. of bitstreams: 1 dantas_prs_me_botfm.pdf: 755908 bytes, checksum: 13b557cdff3e77e3ac4dd782fe68a76e (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Avaliar o prognóstico da mola hidatiforme (MH) e tratamento da neoplasia trofoblástica gestacional (NTG) pós-molar acompanhadas no Centro de Referência para Doenças Trofoblásticas (CDT) versus outras instituições (OI). Estudo de coorte que incluiu 270 pacientes com MH (204 pacientes acompanhas do CDT-Botucatu, onde essa investigação está sendo realizada, e 66 pacientes inicialmente acompanhadas em OI). Todas as pacientes foram registradas no banco de dados do CDT-Botucatu (Universidade Estadual Paulista, Brasil) entre janeiro de 1990 e dezembro de 2009. O prognóstico da MH, bem como as características da NTG e seu desfecho foram analisados e comparados de acordo com o local de seguimento pós-molar. As seguintes variáveis de confundimento foram incluídas: idade (anos), número de gestação, paridade, número de abortamentos, e o tipo de MH (Completa/Parcial). O desfecho da NTG pós-molar consoante o local de seguimento pós-molar foi comparado utilizando-se o teste de Mann-Whitney, teste do Qui-Quadrado ou teste Exato de Fisher. NTG pós-molar ocorreu em 34 (34/204=16,7%) das pacientes que foram acompanhadas no CDT, e em 27 (27/66=40,9%) daquelas que realizaram o seguimento em OI. Pacientes que foram seguidas no CDT cursaram com características de NTG com melhor prognóstico, tais como: menor índice de metástases (5,8% versus 48%,p=0,003), menor mediana do escore FIGO 2000 [2,00 (1,00; 3,00) versus 4,00 (2,00; 7,00), p=0,003] e início mais precoce da quimioterapia em semanas [7,0 (6,0; 10,0) versus 10,0 (7,0; 16,0), p=0,04]. NTG de alto-risco não foi observada em nenhuma paciente submetida ao EUCDT, ocorrendo em 29% daquelas que foram acompanhadas em OI (p<0,001). Quimioterapia com múltiplos agentes para o tratamento da NTG pós-molar foi necessária em dois casos... / To review treatment results of gestational trophoblastic neoplasia (GTN) after hydatidiform mole (HM) evacuation at a referral center (ERC) versus HM evacuation at other institutions (EOI). This cohort study included 270 patients undergoing HM evacuation (204 at the study referral center and 66 at other institutions). All patients were registered in the database of Botucatu Trophoblastic Diseases Center (São Paulo State University, Brazil) between January 1990 and December 2009. GTN characteristics and outcomes were analyzed and compared according to HM evacuation setting. The confounding variables assessed included age (years), number of gestations, parity, number of abortions, and HM type (Complete/Partial). Post-molar GTN outcomes according to HM evacuation setting were compared using Mann-Whitney’s test, Chi-square test, or Fisher’s exact test. Post-molar GTN occurred in 34 (34/204=16.7%) patients undergoing HM evacuation at the referral center, and in 27 (27/66=40.9%) of those undergoing HM evacuation in other institutions. Patients undergoing HM ERC showed GTN characteristics indicative of better prognosis such as: lower metastasis rate (5.8% versus 48%, p=0.003), lower median FIGO 2000 score [2.00 (1.00; 3.00) versus 4.00 (2.00; 7.00), p=0.003], and earlier chemotherapy onset in weeks [7.0 (6.0; 10.0) versus 10.0 (7.0; 16.0), p=0.04]. High-risk post-molar GTN was observed in no patient undergoing HM ERC, and in 29% of those undergoing HM EOI (p<0.001). Multi-agent chemotherapy for the treatment of post-molar GTN was required in two cases of HM evacuation at the referral center (5.9%) and in eight cases of HM EOI (29.6%) (p=0.017). Median time interval between chemotherapy onset and hCG. normalization in weeks was shorter among patients undergoing HM ERC [9.00 (6.25; 12.0) versus... (Complete abstract click electronic access below)