Immunotherapy in the treatment of chemoresistant gestational trophoblastic neoplasia - systematic review with a presentation of the first 4 Brazilian cases

Abstract Objective To evaluate the efficacy of immunotherapy for GTN treatment after methotrexate-resistance or in cases of multiresistant disease, through a systematic review, as well as to present the first 4 Brazilian cases of immunotherapy for GTN treatment. Methods Three independent researchers searched five electronic databases (EMBASE, LILACS, Medline, CENTRAL and Web of Science), for relevant articles up to February/2023 (PROSPERO CRD42023401453). The quality assessment was performed using the Newcastle Ottawa scale for case series and case reports. The primary outcome of this study was the occurrence of complete remission. The presentation of the case reports was approved by the Institutional Review Board. Results Of the 4 cases presented, the first was a low-risk GTN with methotrexate resistance unsuccessfully treated with avelumab, which achieved remission with sequential multiagent chemotherapy. The remaining 3 cases were high-risk multiagent-resistant GTN that were successfully treated with pembrolizumab, among which there were two subsequent gestations, one of them with normal pregnancy and healthy conceptus. Regarding the systematic review, 12 studies were included, only one of them on avelumab, showing a 46.7% complete remission rate. The remaining 11 studies were on pembrolizumab, showing an 86.7% complete remission rate, regardless of tumor histology. Both immunotherapies showed good tolerability, with two healthy pregnancies being recorded: one after avelumb and another after pembrolizumab. Conclusion Immunotherapy showed effectiveness for GTN treatment and may be especially useful in cases of high-risk disease, where pembrolizumab achieves a high therapeutic response, regardless of the histological type, and despite prior chemoresistance to multiple lines of treatment.

Neutrophil/lymphocyte ratio and other blood cell component counts are not associated with the development of postmolar gestational trophoblastic neoplasia.

OBJECTIVE: To relate preevacuation platelet count and leukogram findings, especially neutrophil/lymphocyte ratios (NLR) and platelet/lymphocyte ratios with the occurrence of gestational trophoblastic neoplasia (GTN) after complete hydatidiform mole (CHM) among Brazilian women. METHODS: Retrospective cohort study of patients with CHM followed at Rio de Janeiro Federal University, from January/2015-December/2020. Before molar evacuation, all patients underwent a medical evaluation, complete blood count and hCG measurement, in addition to other routine preoperative tests. The primary outcome was the occurrence of postmolar GTN. RESULTS: From 827 cases of CHM treated initially at the Reference Center, 696 (84.15%) had spontaneous remission and 131 (15.85%) developed postmolar GTN. Using optimal cut-offs from receiver operating characteristic curves and multivariable logistic regression adjusted for the possible confounding variables of age and preevacuation hCG level (already known to be associated with the development of GTN) we found that ≥2 medical complications at presentation (aOR: 1.96, CI 95%: 1.29-2.98, p<0.001) and preevacuation hCG ≥100,000 IU/L (aOR: 2.16, CI 95%: 1.32-3.52, p<0.001) were significantly associated with postmolar GTN after CHM. However, no blood count profile findings were able to predict progression from CHM to GTN. CONCLUSION: Although blood count is a widely available test, being a low-cost test and mandatory before molar evacuation, and prognostic for outcome in other neoplasms, its findings were not able to predict the occurrence of GTN after CHM. In contrast, the occurrence of medical complications at presentation and higher preevacuation hCG levels were significantly associated with postmolar GTN and may be useful to guide individualized clinical decisions in post-molar follow-up and treatment of these patients.

Fragmentos da história da cesariana / Fragments of the caesarean history

Relatos da operação cesariana permeiam a saga da humanidade e ilustram a historia da Medicina. Figura em diversas civilizações primevas, feita entre babilônicos, romanos e hindus. Chegou até nós alternado uma historia trágica de morte, até sua banalização nos dias atuais, sempre cercada por polêmicas apaixonadas, essa cirurgia figura entre as mais realizadas em todo o mundo...(AU)

Reports of cesarean section permeate the saga of humanity and illustrate the history of Medicine. It figured in several ancient civilizations, reported between Babylonians, Romans and Hindus. It has come to us altenadoting a tragic death story, until its banalization in the present day, always surround by passionate polemics, this surgery is one of the most performed in the world...(AU)

Challenges in the diagnosis and treatment of gestational trophoblastic neoplasia worldwide.

Gestational trophoblastic neoplasia (GTN) is a rare tumor that originates from pregnancy that includes invasive mole, choriocarcinoma (CCA), placental site trophoblastic tumor and epithelioid trophoblastic tumor (PSTT/ETT). GTN presents different degrees of proliferation, invasion and dissemination, but, if treated in reference centers, has high cure rates, even in multi-metastatic cases. The diagnosis of GTN following a hydatidiform molar pregnancy is made according to the International Federation of Gynecology and Obstetrics (FIGO) 2000 criteria: four or more plateaued human chorionic gonadotropin (hCG) concentrations over three weeks; rise in hCG for three consecutive weekly measurements over at least a period of 2 weeks or more; and an elevated but falling hCG concentrations six or more months after molar evacuation. However, the latter reason for treatment is no longer used by many centers. In addition, GTN is diagnosed with a pathological diagnosis of CCA or PSTT/ETT. For staging after a molar pregnancy, FIGO recommends pelvic-transvaginal Doppler ultrasound and chest X-ray. In cases of pulmonary metastases with more than 1 cm, the screening should be complemented with chest computed tomography and brain magnetic resonance image. Single agent chemotherapy, usually Methotrexate (MTX) or Actinomycin-D (Act-D), can cure about 70% of patients with FIGO/World Health Organization (WHO) prognosis risk score ≤ 6 (low risk), reserving multiple agent chemotherapy, such as EMA/CO (Etoposide, MTX, Act-D, Cyclophosphamide and Oncovin) for cases with FIGO/WHO prognosis risk score ≥ 7 (high risk) that is often metastatic. Best overall cure rates for low and high risk disease is close to 100% and > 95%, respectively. The management of PSTT/ETT differs and cure rates tend to be a bit lower. The early diagnosis of this disease and the appropriate treatment avoid maternal death, allow the healing and maintenance of the reproductive potential of these women.

How do maternal factors impact preeclampsia prediction in Brazilian population?

Objective: To evaluate the impacts of maternal risk factors described by the Fetal Medicine Foundation's 2012 algorithm (FMF2012) in a Brazilian population. Methods: All singleton pregnancies submitted to first-trimester preeclampsia (PE) screening using the FMF2012 algorithm were considered for study inclusion. Maternal factors, recorded via a patient questionnaire, were described and compared between PE outcome groups. A Gaussian regression model was derived to measure the effects of maternal factors, and to identify factors that contributed significantly (p < .05) to the alteration of gestational age at delivery, in pregnancies with PE. Results: Of the 1934 cases considered for study inclusion, the final sample consisted of 1531 cases. The sample included 120 (7.8%) cases of PE, of which 26 (1.7%) were preterm PE (PE < 37 weeks) and 11 (0.72%) were early PE (PE < 34 weeks). The PE rate did not differ according to ethnicity, smoking, family history of PE, or use of assisted reproductive technology. Significant differences (p < .05) between the normal and PE groups in maternal age, maternal weight, previous history of PE, chronic hypertension, and types 1 and 2 diabetes were detected. Conclusions: The significance and magnitude of associations of maternal factors in our sample differed from those incorporated in the FMF2012 model, implying the need to derive a fitted model for our population.

Manual Compared With Electric Vacuum Aspiration for Treatment of Molar Pregnancy.

OBJECTIVE: To evaluate uterine evacuation of patients with molar pregnancy, comparing manual with electric vacuum aspiration. METHODS: This is a retrospective cohort study of patients with molar pregnancy followed at the Rio de Janeiro Trophoblastic Disease Center from January 2007 to December 2016. The individual primary study outcomes were incomplete uterine evacuation, uterine perforation, development of uterine synechia, and development of postmolar gestational trophoblastic neoplasia. Secondary endpoints were other features of the perioperative outcomes (operative time, rate of transfusion, hemoglobin change, length of stay) and the clinical course of neoplasia (Prognostic Risk Score, presence of metastases, time to remission, and need for multiagent chemotherapy). RESULTS: Among 1,727 patients with molar pregnancy, 1,206 underwent electric vacuum aspiration and 521 underwent manual vacuum aspiration. After human chorionic gonadotropin normalization, patients with benign molar pregnancy were followed for 6 months and patients treated for gestational trophoblastic neoplasia were followed for 12 months. Baseline risk factors for gestational trophoblastic neoplasia and demographic features were similar between the treatment groups. Uterine synechia developed less frequently after manual vacuum aspiration than after electric vacuum aspiration, 6 of 521 vs 63 of 1,206 (adjusted odds ratio [OR] 0.21, 95% CI 0.09-0.49), despite no differences in the occurrence of incomplete uterine evacuation, 65 of 521 vs 161 of 1,206 (adjusted OR 0.93, 95% CI 0.69-1.27), development of postmolar gestational trophoblastic neoplasia, 90 of 521 vs 171 of 1,206 (adjusted OR 1.26, 95% CI 0.96-1.67), or the need for multiagent chemotherapy, 22 of 521 vs 41 of 1,206 (adjusted OR 0.81, 95% CI 0.73-1.28). CONCLUSION: Manual vacuum aspiration appears to be similar to electric vacuum aspiration for treatment of molar pregnancy and may be associated with less development of uterine synechia.

Assistance flowchart for pain management in a Neonatal Intensive Care Unit / Flujograma asistencial para manejo del dolor en Unidad de Terapia Intensiva Neonatal / Fluxograma assistencial para manejo da dor em Unidade de Terapia Intensiva Neonatal

ABSTRACT Objective: To describe and discuss the process of developing a flowchart collectively constructed by the health team of a Neonatal Intensive Care Unit for the management of neonatal pain. Method: This is a descriptive and an exploratory study with a qualitative approach that used Problem-Based Learning as a theoretical-methodological framework in the process of developing the assistance flowchart for the management of neonatal pain. Results: Based on this methodology, there was training in service and the discussion of key points of pain management by the health team, which served as input for the construction of the flowchart. Final considerations: The assistance flowchart for pain management, based on scientific evidence, provided means to facilitate the decision-making of the health team regarding the pain of the newborn. It is suggested to use the flowchart frequently to promote the permanent education of the team and identify possible points to be adjusted.

RESUMEN Objetivo: Describir y discutir el proceso de desarrollo de un diagrama de flujo construido colectivamente por el equipo de salud de una Unidad de Terapia Intensiva Neonatal para el manejo del dolor neonatal. Método: Se trata de un estudio descriptivo, exploratorio, con un abordaje cualitativo que utilizó el Aprendizaje Basado en Problemas como referencial teórico-metodológico en el proceso de desarrollo del diagrama de flujo asistencial del manejo del dolor neonatal. Resultados: A partir de esta metodología ocurrió una capacitación en servicio y la discusión de puntos claves del manejo del dolor por el equipo de salud, los cuales sirvieron de subsidios para la construcción del diagrama de flujo. Consideraciones finales: El flujograma asistencial del manejo del dolor, construido a partir de evidencias científicas, proporcionó medios para facilitar la toma de decisión del equipo de salud frente al dolor del recién nacido. Se sugiere la aplicación del diagrama de flujo con frecuencia para promover la educación permanente del equipo e identificar posibles puntos a ser ajustados.

RESUMO Objetivo: Descrever e discutir o processo de desenvolvimento de um fluxograma construído coletivamente pela equipe de saúde de uma Unidade de Terapia Intensiva Neonatal para o manejo da dor neonatal. Método: Trata-se de um estudo descritivo, exploratório, com abordagem qualitativa que usou a Aprendizagem Baseada em Problemas como referencial teórico-metodológico no processo de desenvolvimento do fluxograma assistencial do manejo da dor neonatal. Resultados: A partir desta metodologia ocorreu uma capacitação em serviço e a discussão de pontos chaves do manejo da dor pela equipe de saúde, que serviram de subsídios para construção do fluxograma. Considerações finais: O fluxograma assistencial do manejo da dor, construído a partir de evidências científicas, forneceu meios para facilitar a tomada de decisão da equipe de saúde frente à dor do recém-nascido. Sugere-se a aplicação do fluxograma com frequência para promover a educação permanente da equipe e identificar possíveis pontos a serem ajustados.

Papel da Apoptose em Obstetrícia / Role of Apoptosis in Obstetrics

Apoptose, ou morte celular programada, é um mecanismo fisiológico universal entre mamíferos que regula o equilíbrio entre proliferação e morte celular a fim de manter a homeostase tecidual. Nesse processo, a apoptose poderá ser iniciada intrinsicamente por via mitocondrial ou, extrinsecamente, mediada por sinalização via receptor de morte ou em resposta a elementos exógenos como citocinas e processos não excludentes, complementares e com ativação cruzada. As moléculas envolvidas no controle das vias de ativação da apoptose são as proteínas anti, pró-apoptóticas e caspases. Esse fenômeno biológico, além de desempenhar um papel importante no controle de diversos processos vitais, está associado a inúmeras complicações da gravidez como toxemia, crescimento intrauterino restrito, parto pré-termo, diabetes gestacional, abortamento, gravidez ectópica e a transformação maligna da mola hidatiforme. No denominador comum dessas doenças está o desconhecimento de sua etiopatogenia e o desenvolvimento/funcionamento placentário anormal. Compreender todas essas alterações deverá interessar não apenas ao pesquisador dessas moléstias, mas também aos clínicos que tratam essas doenças no intuito de se incorporar novas tecnologias na rotina médica e na melhoria das perspectivas prognósticas e terapêuticas dentro da obstetrícia.(AU)

Apoptosis, or programmed cell death, is a universal physiological mechanism in mammals, which regulates the balance between cell proliferation and death in order to maintain tissue homeostasis. In this process, apoptosis can be initiated intrinsically or extrinsically by mitochondrial pathway, mediated by death receptor signaling or in response to exogenous factors such as cytokines and processes not mutually exclusive, complementary and cross-activation. The molecules involved in the control of apoptosis activation pathways are anti and pro-apoptotic proteins as well as caspases. This biological phenomenon, besides play an important role in the control of many vital processes, is associated with many complications of pregnancy such as toxemia, intrauterine growth, preterm birth, gestational diabetes, miscarriage, ectopic pregnancy and malignant in transformation hydatiform mole. The common denominator of these diseases is the lack of knowledge about its pathogenesis and development/abnormal placental function. Understand all these changes should interest not only to the researchers, but also for clinicians who treat these diseases in order to incorporate new technologies in the medical routine and in improving prognostic and therapeutic perspectives in obstetrics.(AU)

A twin pregnancy with a hydatidiform mole and a coexisting live fetus: prenatal diagnosis, treatment, and follow-up.

Twin molar pregnancy with a hydatidiform mole and a coexisting live fetus is a rare form of gestational trophoblastic disease associated with an increased risk of obstetric complications and poor perinatal outcome. Prenatal diagnosis is essential for couple counseling and follow-up in Tertiary Reference Centers. Magnetic resonance imaging is important for the diagnostic differentiation of placental mesenchymal dysplasia and exclusion of myometrial invasion. Here we present a case of twin molar pregnancy with a hydatidiform mole and a coexisting live fetus diagnosed at gestational week 14 using two-dimensional (2D) and three-dimensional (3D) ultrasound and magnetic resonance imaging. We also describe the obstetric management and postmolar follow-up.

Clinical and radiological correlations in patients with gestational trophoblastic disease.

Gestational trophoblastic disease is an abnormality of pregnancy that encompasses a group of diseases that differ from each other in their propensity for regression, invasion, metastasis, and recurrence. In the past, it was common for patients with molar pregnancy to present with marked symptoms: copious bleeding; theca lutein cysts; uterus larger than appropriate for gestational age; early preeclampsia; hyperemesis gravidarum; and hyperthyroidism. Currently, with early diagnosis made by ultrasound, most patients are diagnosed while the disease is still in the asymptomatic phase. In cases of progression to trophoblastic neoplasia, staging-typically with Doppler flow studies of the pelvis and chest X-ray, although occasionally with computed tomography or magnetic resonance imaging-is critical to the choice of an appropriate antineoplastic therapy regimen. Because it is an unusual and serious disease that affects women of reproductive age, as well as because its appropriate treatment results in high cure rates, it is crucial that radiologists be familiar with gestational trophoblastic disease, in order to facilitate its early diagnosis and to ensure appropriate follow-up imaging.

Doença trofoblástica gestacional é anomalia da gravidez que engloba um grupo de doenças derivadas do trofoblasto, diferentes entre si na propensão para regressão, invasão, metástase e recidiva. No passado, era comum a paciente portadora de gravidez molar apresentar sintomas exuberantes: hemorragia copiosa, cistos tecaluteínicos, útero aumentado para a idade gestacional, pré-eclâmpsia precoce, hiperêmese e hipertireoidismo. Atualmente, com o diagnóstico precoce feito pela ultrassonografia, a maioria das pacientes é diagnosticada ainda na fase assintomática. Nos casos em que há progressão para neoplasia trofoblástica gestacional, o estadiamento feito com a dopplerfluxometria pélvica e a radiografia de tórax, eventualmente com a tomografia computadorizada e a ressonância magnética, é fundamental na avaliação da escolha do tratamento antineoplásico. Por ser uma doença incomum e grave, que acomete mulheres no menacme, mas cujo tratamento adequado determina elevadas taxas de cura, é fundamental que os radiologistas estejam familiarizados com essa entidade clínica, a fim de auxiliar no diagnóstico precoce e promover seu correto acompanhamento imaginológico.

Clinical and radiological correlations in patients with gestational trophoblastic disease / Correlações clinicorradiológicas em pacientes com doença trofoblástica gestacional

Abstract Gestational trophoblastic disease is an abnormality of pregnancy that encompasses a group of diseases that differ from each other in their propensity for regression, invasion, metastasis, and recurrence. In the past, it was common for patients with molar pregnancy to present with marked symptoms: copious bleeding; theca lutein cysts; uterus larger than appropriate for gestational age; early preeclampsia; hyperemesis gravidarum; and hyperthyroidism. Currently, with early diagnosis made by ultrasound, most patients are diagnosed while the disease is still in the asymptomatic phase. In cases of progression to trophoblastic neoplasia, staging-typically with Doppler flow studies of the pelvis and chest X-ray, although occasionally with computed tomography or magnetic resonance imaging-is critical to the choice of an appropriate antineoplastic therapy regimen. Because it is an unusual and serious disease that affects women of reproductive age, as well as because its appropriate treatment results in high cure rates, it is crucial that radiologists be familiar with gestational trophoblastic disease, in order to facilitate its early diagnosis and to ensure appropriate follow-up imaging.

Resumo Doença trofoblástica gestacional é anomalia da gravidez que engloba um grupo de doenças derivadas do trofoblasto, diferentes entre si na propensão para regressão, invasão, metástase e recidiva. No passado, era comum a paciente portadora de gravidez molar apresentar sintomas exuberantes: hemorragia copiosa, cistos tecaluteínicos, útero aumentado para a idade gestacional, pré-eclâmpsia precoce, hiperêmese e hipertireoidismo. Atualmente, com o diagnóstico precoce feito pela ultrassonografia, a maioria das pacientes é diagnosticada ainda na fase assintomática. Nos casos em que há progressão para neoplasia trofoblástica gestacional, o estadiamento feito com a dopplerfluxometria pélvica e a radiografia de tórax, eventualmente com a tomografia computadorizada e a ressonância magnética, é fundamental na avaliação da escolha do tratamento antineoplásico. Por ser uma doença incomum e grave, que acomete mulheres no menacme, mas cujo tratamento adequado determina elevadas taxas de cura, é fundamental que os radiologistas estejam familiarizados com essa entidade clínica, a fim de auxiliar no diagnóstico precoce e promover seu correto acompanhamento imaginológico.

Cesarean section by maternal request / Cesariana a pedido materno

ABSTRACT Cesarean section by maternal request is the one performed on a pregnant woman without medical indication and without contraindication to vaginal delivery. There is great controversy over requested cesarean section. Potential risks include complications in subsequent pregnancies, such as uterine rupture, placenta previa and accreta. Potential benefits of requested cesareans include a lower risk of postpartum hemorrhage in the first cesarean and fewer surgical complications compared with vaginal delivery. Cesarean section by request should never be performed before 39 weeks.

RESUMO A cesariana a pedido materno é aquela realizada em uma gestante sem indicações médicas e sem contraindicação para tentativa do parto vaginal. Existe grande controvérsia sobre a realização da cesariana a pedido. Riscos potenciais da cesariana a pedido incluem complicações em gravidezes subsequentes, tais como: rotura uterina, placenta prévia e acretismo. Potenciais benefícios da cesariana a pedido englobam um menor risco de hemorragia pós-parto na primeira cesariana e menos complicações cirúrgicas quando comparada ao parto vaginal. A cesariana a pedido jamais deve ser realizada antes de 39 semanas.

Changing Trends in the Clinical Presentation and Management of Complete Hydatidiform Mole Among Brazilian Women.

OBJECTIVE: The aim of the study was to evaluate potential changes in the clinical, diagnostic, and therapeutic parameters of complete hydatidiform mole in the last 25 years in Brazil. METHODS: A retrospective cohort study was conducted involving the analysis of 2163 medical records of patients diagnosed with complete hydatidiform mole who received treatment at the Rio de Janeiro Reference Center for Gestational Trophoblastic Disease between January 1988 and December 2012. For the statistical analysis of the natural history of the patients with complete molar pregnancies, time series were evaluated using the Cox-Stuart test and adjusted by linear regression models. RESULTS: A downward linear temporal trend was observed for gestational age of complete hydatidiform mole at diagnosis, which is also reflected in the reduced occurrence of vaginal bleeding, hyperemesis and pre-eclampsia. We also observed an increase in the use of uterine vacuum aspiration to treat molar pregnancy. Although the duration of postmolar follow-up was found to decline, this was not accompanied by any alteration in the time to remission of the disease or its progression to gestational trophoblastic neoplasia. CONCLUSIONS: Early diagnosis of complete hydatidiform mole has altered the natural history of molar pregnancy, especially with a reduction in classical clinical symptoms. However, early diagnosis has not resulted in a reduction in the development of gestational trophoblastic neoplasia, a dilemma that still challenges professionals working with gestational trophoblastic disease.

Atualização no diagnóstico e tratamento da gravidez molar / Update on the diagnosis and treatment of molar pregnancy

A doença trofoblástica gestacional (DTG) é um termo aplicado a um grupo de tumores relacionados à gestação, caracterizado por entidades clínicas benignas (mola hidatiforme ? MH) e malignas (neoplasia trofoblástica gestacional ? NTG). Os principais desafios para o tratamento das pacientes com MH abrangem o diagnóstico precoce, esvaziamento uterino imediato e seguimento pós-molar regular com dosagem sérica de hCG, melhorando assim o prognóstico das pacientes, sua qualidade de vida e resultados reprodutivos. A atualização das estratégias diagnósticas e terapêuticas envolvidas no tratamento da DTG, foco deste trabalho, tem por objetivo melhorar esse cenário, contribuindo para o maior conhecimento sobre o assunto.

The gestational trophoblastic disease (GTD) is a term applied to a group of pregnancy related tumors, characterized by benign clinical entities (hydatidiform mole ? HM) and malignant ones (gestational trophoblastic neoplasia ? GTN). The main challenges for treatment of patients with HM include early diagnosis, immediate uterine evacuation and systematic post-molar follow-up with seric dosage of hCG, improving the prognosis of patients, their quality of life and reproductive outcomes. The focus of the present paper is the update of diagnostic and therapeutic strategies involved in the treatment of GTD aiming to improve this scenario to enhance the knowledge on the subject.

Alterações hepáticas da gravidez / Liver disorders in pregnancy

A gestação é um período de significativas modificações no organismo materno, que objetivam promover a homeostase do binômio materno-fetal. Sob o ponto de vista hepático, demais das alterações conspícuas à gravidez, deve o obstetra detectar precocemente anomalias envolvendo o fígado, que complicam até 3% das gestações e são responsáveis por elevada mortalidade materna e perinatal. Por outro lado, certas doenças hepáticas têm sua história natural modificada quando ocorrem durante a gestação, demandando cuidados especiais de uma equipe multidisciplinar que envolva o obstetra e o hepatologista. Este artigo revisa as modificações fisiológicas do sistema hepático na gravidez, assim como suas alterações hepáticas mais prevalentes no Brasil. O objetivo é auxiliar e fornecer orientações ao obstetra e guiar o melhor cuidado das pacientes a fim de prevenir e reduzir as complicações hepáticas na gravidez.(AU)

Pregnancy is a period of significant changes in the mother's organism aimed at promoting the mother-fetus homeostasis. From the hepatic standpoint, the obstetrician should detect early the abnormalities attacking the liver, which complicates up to 3% of pregnancies and are responsible for high rates of maternal and perinatal mortality. On the other hand, some liver diseases have their natural evolution changed when they occur during the pregnancy, requiring special care of a multidisciplinary team involving obstetrician and hepatologist specialists. This study presents the physiological changes of the hepatic system during pregnancy, as well as the most prevalent pregnancy hepatic disorders occurring in Brazil. It aims to help the obstetrician and guide the best patient care to prevent and reduce hepatic complications in pregnancy.(AU)

[Gestational trophoblastic neoplasia after spontaneous normalization of human chorionic gonadotropin in patient with partial hydatidiform mole]. / Neoplasia trofoblástica gestacional após normalização espontânea da gonadotrofina coriônica humana em paciente com mola hidatiforme parcial.

We report here a case of gestational trophoblastic neoplasia after spontaneous normalization of human chorionic gonadotropin in a patient with a partial hydatidiform mole. This is the second occurrence of this event to be reported and the first one with proven immunohistochemical evidence. Besides showing the treatment for this pregnancy complication, this case report discusses the possibility of reducing the duration of post-molar follow-up, as well as strategies for early recognition of gestational trophoblastic neoplasia after spontaneous remission of molar pregnancy.

Neoplasia trofoblástica gestacional após normalização espontânea da gonadotrofina coriônica humana em paciente com mola hidatiforme parcial / Gestational trophoblastic neoplasia after spontaneous normalization of human chorionic gonadotropin in patient with partial hydatidiform mole

Neste relato, é apresentado um caso de neoplasia trofoblástica gestacional após normalização espontânea de gonadotrofina coriônica humana em paciente com mola hidatiforme parcial. Trata-se da segunda ocorrência publicada desse evento e a primeira em que há comprovação imuno-histoquímica. No bojo dessa apresentação, ademais de mostrar o tratamento para essa intercorrência da gravidez, discute-se a possibilidade de redução da duração do seguimento pós-molar, assim como estratégias para o precoce reconhecimento da neoplasia trofoblástica gestacional após a remissão espontânea da gravidez molar.

We report here a case of gestational trophoblastic neoplasia after spontaneous normalization of human chorionic gonadotropin in a patient with a partial hydatidiform mole. This is the second occurrence of this event to be reported and the first one with proven immunohistochemical evidence. Besides showing the treatment for this pregnancy complication, this case report discusses the possibility of reducing the duration of post-molar follow-up, as well as strategies for early recognition of gestational trophoblastic neoplasia after spontaneous remission of molar pregnancy.

Mola hidatiforme parcial recorrente evoluindo para neoplasia trofoblástica gestacional / Recurrent partial hydatidiform mole evolving to gestational trophoblastic neoplasia

Mola hidatiforme parcial recorrente é evento em que há repetição da mola hidatiforme parcial. Há cerca de 100 casos relatados na literatura e dúvida se essa entidade pode evolver para neoplasia trofoblástica gestacional pós-molar. Apresenta-se relato de caso de paciente com recorrência de mola hidatiforme parcial em que houve aumento de embriopatia, bem como transformação maligna da mola parcial recorrente. Empregou-se quimioterapia com Methotrexate para induzir cura. Não obstante seja ocorrência rara, a importância deste relato encontra-se na evidência de neoplasia trofoblástica gestacional em recorrência de mola hidatiforme parcial, determinando vigilância hormonal rigorosa para detectar a malignização desses blastomas.

Recurrent partial hydatidiform mole is an event of repetitive partial hydatidiform mole. It has been reported around 100 cases in the literature and it is still unclear if this entity can evolve to postmolar gestational trophoblastic neoplasia. In this report, it is presented a case of recurrent partial hydatidiform mole with an increase in embriologic alterations, as well as malignization of recurrent partial hydatidiform mole. Chemotherapy with Methotrexate regimen was used to induce remission. Although rare, the importance of this report relies on the evidence of gestational trophoblastic neoplasia in recurrent partial hydatidiform mole, demanding straight hormonal surveillance to detect malignization of these tumors.

Complicações clínicas da gravidez molar / Clinical complications of hydatidiform mole

A gravidez molar, espectro benigno da doença trofoblástica gestacional, representa uma complicação obstétrica da primeira metade da gestação. De maneira geral, cursa com sintomatologia exuberante: hemorragia, útero aumento para a idade gestacional, cistose ovariana e pré-eclâmpsia precoce; chegando mesmo a graves situações clínicas de hipertireoidismo e insuficiência respiratória.Todavia, devido ao diagnóstico precoce da mola hidatiforme, ainda no primeiro trimestre, mercê da ultrassonografia, houve uma importante redução na ocorrência desses sintomas; contribuindo para que a condução desses casos excepcionais ficasse confinada aos Centros de Referência. É objetivo desse artigo apresentar ao obstetra brasileiro uma revisão das complicações clínicas da gravidez molar, atualizando-o no diagnóstico precoce e tratamento dessas condições clínicas que podem ser potencialmente ameaçadoras à vida da gestante e de seu concepto.(AU)

The molar pregnancy, in the benign gestational trophoblastic disease spectrum, represents an obstetric complication of first half of gestation. In general, runs with exuberant symptoms: bleeding, uterus increase for gestational age, ovarian cistose and early preeclampsia; even serious clinical situations of hyperthyroidism and respiratory failure. However, due to the early diagnosis of hydatidiform mole, still in the first trimester, through ultrasound, there was a significant reduction in the occurrence of these symptoms; contributing so that the conduct of these exceptional cases could be confined to the centers of reference. The purpose of this article is to present to the Brazilian obstetrician a review of clinical complications of molar pregnancy, updating it in the early diagnosis and treatment of clinical conditions that can be potentially threatening to the life of the pregnant woman and her fetus.(AU)