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.

Predictors for single-agent resistance in FIGO score 5 or 6 gestational trophoblastic neoplasia: a multicentre, retrospective, cohort study.

BACKGROUND: Patients with gestational trophoblastic neoplasia who have an International Federation of Gynaecology and Obstetrics (FIGO) risk score of 5 or 6 usually receive non-toxic single-agent chemotherapy as a first-line treatment. Previous studies suggest that only a third of patients have complete remission, with the remaining patients requiring toxic multiagent chemotherapy to attain remission. As stratification factors are unknown, some centres offer multiagent therapy upfront, resulting in overtreatment of many patients. We aimed to identify predictive factors for resistance to single-agent therapy to inform clinicians on which patients presenting with a FIGO score of 5 or 6 are likely to benefit from upfront multiagent chemotherapy. METHODS: We did a multicentre, retrospective, cohort study of patients with gestational trophoblastic neoplasia presenting with a FIGO score of 5 or 6, who received treatment at three gestational trophoblastic neoplasia reference centres in the UK, Brazil, and the USA between Jan 1, 1964, and Dec 31, 2018. All patients who had been followed up for at least 12 months after remission were included. Patients were excluded if they had received a non-standard single-agent treatment (eg, etoposide); had been given a previously established first-line multiagent chemotherapy regimen; or had incomplete data for our analyses. Patient data were retrieved from medical records. The primary outcome was the incidence of chemoresistance after first-line or second-line single-agent chemotherapy. Variables associated with chemoresistance to single-agent therapies were identified by logistic regression analysis. In patient subgroups defined by choriocarcinoma histology and metastatic disease status, we did bootstrap modelling to define thresholds of pretreatment human chorionic gonadotropin concentrations and identify groups of patients with a greater than 80% risk (ie, a positive predictive value [PPV] of 0·8) of resistance to single-agent chemotherapy. FINDINGS: Of 5025 patients with low-risk gestational trophoblastic neoplasia, we identified 431 patients with gestational trophoblastic neoplasia presenting with a FIGO risk score of 5 or 6. All patients were followed up for a minimum of 2 years. 141 (40%) of 351 patients developed resistance to single-agent treatments and required multiagent chemotherapy to achieve remission. Univariable and multivariable logistic regression revealed metastatic disease status (multivariable logistic regression analysis, odds ratio [OR] 1·9 [95% CI 1·1-3·2], p=0·018), choriocarcinoma histology (3·7 [1·9-7·4], p=0·0002), and pretreatment human chorionic gonadotropin concentration (2·8 [1·9-4·1], p<0·0001) as significant predictors of resistance to single-agent therapies. In patients with no metastatic disease and without choriocarcinoma, a pretreatment human chorionic gonadotropin concentration of 411 000 IU/L or higher yielded a PPV of 0·8, whereas in patients with either metastases or choriocarcinoma, a pretreatment human chorionic gonadotropin concentration of 149 000 IU/L or higher yielded the same PPV for resistance to single-agent therapy. INTERPRETATION: Approximately 60% of women with gestational trophoblastic neoplasia presenting with a FIGO risk score of 5 or 6 achieve remission with single-agent therapy; almost all remaining patients have complete remission with subsequent multiagent chemotherapy. Primary multiagent chemotherapy should only be given to patients with metastatic disease and choriocarcinoma, regardless of pretreatment human chorionic gonadotropin concentration, or to those defined by our new predictors. FUNDING: None. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

Epilepsia no período gravídico-puerperal / Epilepsy in puerperal-pregnancy period

A epilepsia, doença cerebral caracterizada pela predisposição à geração de crises epilépticas, representa a patologia neurológica grave mais frequente na gravidez. Quando não acompanhada corretamente, possui um acentuado nível de morbimortalidade materno-fetal, sendo especialmente relacionada a riscos de convulsão materna na gestação e malformações fetais. Este artigo discute o acompanhamento da gestante epiléptica, trazendo recomendações de cuidados no período pré-concepcional, manejo durante o pré-natal, condução do trabalho de parto, peculiaridades no puerpério e tratamento de crises convulsivas, quando necessário. Serão abordados tanto aspectos de tratamento farmacológico quanto de monitoramento e orientações gerais, com o objetivo de contribuir para um suporte mais abrangente e adequado a esse grupo mais vulnerável de pacientes sob o cuidado do médico ginecologista-obstetra e neurologista.(AU)

Epilepsy, which is a brain disease defined for a greater predisposition for epileptic crisis, represents the most frequent neurological pathology during pregnancy. Without proper monitoring it is related to high morbidity and mortality to both mother and baby, especially due to the risks of mother seizure during pregnancy and fetus malformation. This article discusses about health care giving and follow-up for the epileptic pregnant women, pointing recommendations for preconception care, prenatal management, labor conduct, peculiarities in puerperium and treatment of convulsive crisis when needed. There will be approached pharmacological and non-pharmacological aspects, such as follow up exams and general orientations, having as a goal to contribute to an more abrangent and proper support of this more vulnerable group of patients under the care responsibility of obstetrician-gynecologist ad neurologist doctors.(AU)

Outcomes in the management of high-risk gestational trophoblastic neoplasia in trophoblastic disease centers in South America.

BACKGROUND: South America has a higher incidence of gestational trophoblastic disease than North America or Europe, but whether this impacts chemotherapy outcomes is unclear. The purpose of this study was to evaluate outcomes among women with high-risk gestational trophoblastic neoplasia (GTN) treated at trophoblastic disease centers in developing South American countries. METHODS: This retrospective cohort study included patients with high-risk GTN treated in three trophoblastic disease centers in South America (Botucatu and Rio de Janeiro, Brazil, and Buenos Aires, Argentina) from January 1990 to December 2014. Data evaluated included demographics, clinical presentation, FIGO stage, WHO prognostic risk score, and treatment-related information. The primary treatment outcome was complete sustained remission by 18 months following completion of therapy or death. RESULTS: Among 1264 patients with GTN, 191 (15.1%) patients had high-risk GTN and 147 were eligible for the study. Complete sustained remission was ultimately achieved in 87.1% of cases overall, including 68.4% of ultra high-risk GTN (score ≥12). Early death (within 4 weeks of initiating therapy) was significantly associated with ultra high-risk GTN, occurring in 13.8% of these patients (p=0.003). By Cox's proportional hazards regression, factors most strongly related to death were non-molar antecedent pregnancy (RR 4.35, 95% CI 1.71 to 11.05), presence of liver, brain, or kidney metastases (RR 4.99, 95% CI 1.96 to 12.71), FIGO stage (RR 3.14, 95% CI 1.52 to 6.53), and an ultra-high-risk prognostic risk score (RR 7.86, 95% CI 2.99 to 20.71). Median follow-up after completion of chemotherapy was 4 years. Among patients followed to that timepoint, the probability of survival was 90% for patients with high-risk GTN (score 7-11) and 60% for patients with ultra-high-risk GTN (score ≥12). CONCLUSION: Trophoblastic disease centers in developing South American countries have achieved high remission rates in high-risk GTN, but early deaths remain an important problem, particularly in ultra-high-risk GTN.

Evaluation of uterine cervical cancer in pregnancy: A cross-sectional study.

OBJECTIVE: Evaluate the prevalence and the regression rate of cytological alteration in pregnant patients below the recommended age by the Brazilian Guidelines for the Screening of Uterine Cervical Cancer Guideline in the prenatal service of Maternidade Escola da Universidade Federal do Rio de Janeiro. STUDY DESIGN: We included the cytopathological exams of all pregnant patients that attended on the outpatient from January 2010 to May 2016. For the identification of the pregnant women, the Management and Integrated System and the Uterine Cervical Cancer Information System of the institution were used. We performed X2 test. The level of significance was 0.05. RESULTS: The study totaled 5825 cytopathological exams, of which 1822 were from pregnant patients ≤ 24 years of age. Only 4.06 % (74/1822) of altered results were found (p < 0.05). The most frequent change was low-grade squamous intraepithelial lesion with a prevalence of 1.92 % (35/1822) whereas high-grade squamous intraepithelial lesion had 0.16 % (3/1822). The regression rate in pregnant patients ≤24 years of age was 34,32 %. CONCLUSION: There was a low prevalence of cytological abnormalities in pregnant patients ≤ 24 years, low frequency of high-grade squamous intraepithelial lesion among the altered cytologies and a high spontaneous regression rate, therefore screening is not recommended before the age determined by the Brazilian Guideline.

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.

Protocolo de agendamento de cirurgias eletivas de uma maternidade escola: estudo metodológico / Protocol of scheduling of elective surgeries of a maternity school: a methodological study / Protocolo para programar las cirugías electivas en una maternidad escuela: estado metodológico

OBJETIVO: construir um protocolo de agendamento e o fluxo assistencial de programação de cirurgias eletivas para o Centro Obstétrico de uma maternidade. MÉTODO: pesquisa metodológica, descritiva, qualitativa, do tipo estudo de caso, operacionalizada em 2015 em uma maternidade do município do Rio de Janeiro. Empregou-se o Planejamento Estratégico Situacional proposto por Carlos Matus, a partir dos momentos explicativo, normativo, estratégico e tático-operacional. RESULTADOS: no momento explicativo procedeu-se com o diagnóstico da realidade de agendamentos do setor cirúrgico; no normativo foram propostas as estratégias de solução para o enfrentamento do problema; no estratégico construiu-se a viabilidade das estratégias de solução a partir de planos de ação; no tático-operacional foram operacionalizadas as ações: construção do protocolo e de um fluxograma de agendamento cirúrgico. CONCLUSÃO: acredita-se que esses instrumentos, que ainda precisam ser testados e validados no cenário do estudo, auxiliarão a gestão dos processos assistenciais do setor.

AIM: to construct a scheduling protocol and the assistance flow of elective surgeries to the Obstetric Center of a maternity ward. METHOD: this is a methodological, descriptive, qualitative research, of the case study type, operationalized in 2015 in a maternity hospital in the city of Rio de Janeiro. The Situational Strategic Planning proposed by Carlos Matus was used, starting from the explanatory, normative, strategic and tactical-operational moments. RESULTS: in the explanatory moment the diagnosis of the reality of scheduling of the surgical sector was performed; in the normative moment the strategies of solution to the confrontation of the problem were proposed; in the strategic moment the viability of the strategies of solution was constructed from action plans; in the tactical-operational moment the following actions were operationalized: construction of the protocol and a flow chart of surgical scheduling. CONCLUSION: it is believed that these instruments, which still need to be tested and validated in the study scenario, will help manage the healthcare processes of the sector.

OBJETIVO: construir un protocolo de programación y el flujo asistencial de programación de cirugías electivas para el Centro Obstétrico de una maternidad. MÉTODO: investigación metodológica, descriptiva, cualitativa, tipo estudio de caso, realizada en el 2015 en una maternidad del municipio de Rio de Janeiro. Se utilizó el Planeamiento Estratégico Situacional propuesto por Carlos Matus, a partir de los momentos explicativo, normativo, estratégico y táctico-operativo. RESULTADOS: en el momento explicativo se procedió con el diagnóstico de la realidad de la programación del sector quirúrgico; en el normativo se propusieron las estrategias de solución para enfrentar el problema; en el estratégico se construyó la viabilidad de las estrategias de solución a partir de planes de acción; en el táctico-operativo se realizaron las acciones: construcción del protocolo y de un diagrama de flujo de la programación quirúrgica. CONCLUSIÓN: se cree que esos instrumentos, que todavía necesitan probarse y validarse en el escenario del estudio, auxiliarán la gestión de los procesos asistenciales del sector.

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.

Epilepsia na gravidez / Epilepsy in pregnancy

As epilepsias constituem uma das mais frequentes condições neurológicas encontradas na gravidez, ocorrendo entre 0,5% e 1% das gestações. O risco de morte materna está aumentado em 10 vezes nas grávidas epilépticas. Na gestante, o diagnóstico adequado é fundamental, já que deve ser afastada a possibilidade de se tratar de crise de eclâmpsia, doença exclusiva do período gravídico-puerperal. A preocupação materna quanto aos efeitos adversos (malformações) das drogas antiepilépticas no bebê pode levar à descontinuação ou redução da dose do medicamento, aumentando o risco de convulsão ou de morte súbita e inesperada na epilepsia (SUDEP). Nesta revisão foi dada atenção única e exclusiva às recomendações do Royal College of Obstetricians and Gynaecologists.(AU)

Epilepsiy is one of the most frequent neurological conditions found in pregnancy, occurring in 0.5 to 1% of pregnancies. The maternal death risk is increased 10-fold in epileptic pregnancies. In pregnant women, its adequate diagnosis is essential, since eclampsia is a differential diagnosis, which is disease exclusive to the pregnancy-puerperal period. Maternal concerns about the adverse effects (malformations) of antiepileptic drugs in the infant may lead to the discontinuation or reduction of the drug dose, increasing the risk of seizure or sudden and unexpected death in epilepsy (SUDEP). In this review exclusive attention was given to the recommendations of the Royal College of Obstetricians and Gynecologists.(AU)

Trombocitopenia na gravidez / Thrombocytopenia in pregnant

A trombocitopenia na mulher grávida é diagnosticada frequentemente pelos obstetras porque a contagem de plaquetas está incluída nos exames de rotina no pré-natal. A trombocitopenia, definida como a contagem de plaquetas inferior a 150.000/mm3, é comum e ocorre em 7-12% das gestações. Algumas causas de trombocitopenia são graves desordens médicas com potencial para morbidade materna e fetal. Ao revés, outras condições, tais como trombocitopenia gestacional, são benignas e não acarretam riscos maternos ou fetais.(AU)

Thrombocytopenia in pregnant women is often diagnosed by obstetricians because platelet count is included in prenatal routine exams. Thrombocytopenia is defined as platelet count below 150,000 / mm3 is common and occurs in 7-12% of pregnancies. Some causes of thrombocytopenia are serious medical disorders with potential for maternal and fetal morbidity. Conversely, other conditions, such as gestational thrombocytopenia, are benign and do not cause maternal or fetal risks.(AU)

Obstrução do Trato Urinário Baixo Fetal / Fetal lower urinary tract obstruction

A obstrução do trato urinário baixo fetal (fetal lower urinary tract obstruction - LUTO) é uma patologia caracterizada por dilatação da bexiga e hidronefrose bilateral causada por obstrução do trato urinário inferior. Sua incidência é de 2,2 em cada 10.000 nascimentos. A etiologia da LUTO inclui a válvula da uretra posterior (VUP), atresia ou estenose uretral. O diagnóstico é feito por ultrassom, que mostra bexiga dilatada, com paredes espessas (megabexiga), e uretra posterior aumentada. O tratamento cirúrgico clássico (derivação vésico-amniótica guiada por ultrassom) estaria indicado quando o líquido amniótico normal começa a diminuir, com aumento da distensão vesical e da hidronefrose. O tratamento inclui a colocação de derivação vésico-amniótica guiado pelo ultrassom e fetoscópica com coagulação a laser. De acordo com a gravidade, a LUTO é classificada nos estágios 1,2 e 3.(AU)

The Fetal Lower Urinary Tract Obstruction (LUTO) is a spectrum of diseases characterized by bladder distension and bilateral hydronephrosis in consequence of the LUTO. The incidence is approximately 2.2 in 10,000 births and it is commonly diagnosed during the late first or early second trimester of pregnancy. The etiologies of LUTO include posterior urethral valves, urethral atresia and urethral stenosis. Complete bladder outlet obstruction (severe LUTO) is associated with high perinatal mortality due to pulmonary hypoplasia and severe renal impairment/damage. The prenatal intervention includes vesicoamniotic shunt placement guided by ultrasound and fetoscopic laser coagulation. It is suggested that LUTO patients could be categorized in three stages according to disease gravity: Stages 1, 2 and 3.(AU)

Uterine artery Doppler flow velocimetry parameters for predicting gestational trophoblastic neoplasia after complete hydatidiform mole, a prospective cohort study.

OBJECTIVES:: Doppler ultrasonography can be used to assess neoangiogenesis, a characteristic feature of postmolar gestational trophoblastic neoplasia. However, there is limited information on whether uterine artery Doppler flow velocimetry parameters can predict gestational trophoblastic neoplasia following a complete hydatidiform mole. The purpose of this study was as follows: 1) to compare uterine blood flow before and after complete mole evacuation between women who developed postmolar gestational trophoblastic neoplasia and those who achieved spontaneous remission, 2) to assess the usefulness of uterine Doppler parameters as predictors of postmolar gestational trophoblastic neoplasia and to determine the best parameters and cutoff values for predicting postmolar gestational trophoblastic neoplasia. METHODS:: This prospective cohort study included 246 patients with a complete mole who were treated at three different trophoblastic diseases centers between 2013 and 2014. The pulsatility index, resistivity index, and systolic/diastolic ratio were measured by Doppler flow velocimetry before and 4-6 weeks after molar evacuation. Statistical analysis was performed using Wilcoxon's test, logistic regression, and ROC analysis. RESULTS:: No differences in pre- and post-evacuation Doppler measurements were observed in patients who developed postmolar gestational trophoblastic neoplasia. In those with spontaneous remission, the pulsatility index and systolic/diastolic ratio were increased after evacuation. The pre- and post-evacuation pulsatility indices were significantly lower in patients with gestational trophoblastic neoplasia (odds ratio of 13.9-30.5). A pre-evacuation pulsatility index ≤1.38 (77% sensitivity and 82% specificity) and post-evacuation pulsatility index ≤1.77 (79% sensitivity and 86% specificity) were significantly predictive of gestational trophoblastic neoplasia. CONCLUSIONS:: Uterine Doppler flow velocimetry measurements, particularly pre- and post-molar evacuation pulsatility indices, can be useful for predicting postmolar gestational trophoblastic neoplasia.

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)

Uterine artery Doppler flow velocimetry parameters for predicting gestational trophoblastic neoplasia after complete hydatidiform mole, a prospective cohort study

OBJECTIVES: Doppler ultrasonography can be used to assess neoangiogenesis, a characteristic feature of postmolar gestational trophoblastic neoplasia. However, there is limited information on whether uterine artery Doppler flow velocimetry parameters can predict gestational trophoblastic neoplasia following a complete hydatidiform mole. The purpose of this study was as follows: 1) to compare uterine blood flow before and after complete mole evacuation between women who developed postmolar gestational trophoblastic neoplasia and those who achieved spontaneous remission, 2) to assess the usefulness of uterine Doppler parameters as predictors of postmolar gestational trophoblastic neoplasia and to determine the best parameters and cutoff values for predicting postmolar gestational trophoblastic neoplasia. METHODS: This prospective cohort study included 246 patients with a complete mole who were treated at three different trophoblastic diseases centers between 2013 and 2014. The pulsatility index, resistivity index, and systolic/diastolic ratio were measured by Doppler flow velocimetry before and 4-6 weeks after molar evacuation. Statistical analysis was performed using Wilcoxon’s test, logistic regression, and ROC analysis. RESULTS: No differences in pre- and post-evacuation Doppler measurements were observed in patients who developed postmolar gestational trophoblastic neoplasia. In those with spontaneous remission, the pulsatility index and systolic/diastolic ratio were increased after evacuation. The pre- and post-evacuation pulsatility indices were significantly lower in patients with gestational trophoblastic neoplasia (odds ratio of 13.9-30.5). A pre-evacuation pulsatility index ≤1.38 (77% sensitivity and 82% specificity) and post-evacuation pulsatility index ≤1.77 (79% sensitivity and 86% specificity) were significantly predictive of gestational trophoblastic neoplasia. CONCLUSIONS: Uterine Doppler flow velocimetry measurements, particularly pre- and post-molar evacuation pulsatility indices, can be useful for predicting postmolar gestational trophoblastic neoplasia.