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. methotrexateresistance disease review EMBASE, EMBASE (EMBASE LILACS Medline Science, Science , Science) February2023 February 2023 February/202 PROSPERO CRD42023401453. CRD42023401453 CRD . CRD42023401453) Board presented lowrisk low risk avelumab chemotherapy highrisk multiagentresistant resistant gestations conceptus 1 included 467 46 7 46.7 rate 867 86 86.7 histology tolerability recorded response type February202 202 February/20 CRD4202340145 46. 8 86. February20 20 February/2 CRD420234014 February2 2 February/ CRD42023401 CRD4202340 CRD420234 CRD42023 CRD4202 CRD420 CRD42 CRD4

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.

RESUMO Doença trofoblástica gestacional inclui um grupo interrelacionado de doenças originadas do tecido placentário, com tendências distintas de invasão local e metástase. A alta sensibilidade das dosagens seriadas de gonadotrofina coriônica humana aliada aos avanços do tratamento quimioterápico tornou a neoplasia trofoblástica gestacional, curável, na maioria das vezes, através da quimioterapia. No entanto, a cirurgia permanece ainda, da maior importância na condução de pacientes com doença trofoblástica gestacional, melhorando seu prognóstico. A cirurgia é necessária no controle de complicações da doença, tais como hemorragia, e em casos de neoplasia resistente/recidivada. Esta revisão discute as indicações e o papel das intervenções cirúrgicas durante o manejo de mulheres com gravidez molar e neoplasia trofoblástica gestacional.

ABSTRACT The Gestational Trophoblastic Disease includes an interrelated group of diseases originating from placental tissue, with distinct behaviors concerning local invasion and metastasis. The high sensitivity of the serial dosages of human chorionic gonadotrophin, combined with advances in chemotherapy treatment, have made gestational trophoblastic neoplasia curable, most often through chemotherapy. However, surgery remains of major importance in the management of patients with gestational trophoblastic disease, improving their prognosis. Surgery is necessary in the control of the disease's complications, such as hemorrhage, and in cases of resistant/relapsed neoplasia. This review discusses the indications and the role of surgical interventions in the management of women with molar pregnancy and gestational trophoblastic neoplasia.

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.

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 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.

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.

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.

OBJETIVO: Avaliar a função endotelial em pacientes com fatores de risco para aterosclerose pela dilatação fluxo-mediada da artéria braquial (DILA) e complexo médio-intimal (CMI) das artérias carótida e braquial. MATERIAIS E MÉTODOS: Estudo transversal, caso controle, no qual foi avaliada a função endotelial pelo DILA e CMI das artérias carótida e braquial e presença ou não de fatores de risco para aterosclerose, em 112 pacientes assim distribuídos: mulheres com fatores de risco (n = 49), mulheres grupo controle (n = 24), homens com fatores de risco (n = 21) e homens grupo controle (n = 18). RESULTADOS: O DILA esteve comprometido significativamente no grupo fator de risco, quando comparado ao controle, independente do sexo: em mulheres, 15,2 × 25,3 (p < 0,01); em homens, 11,8 × 16,8 (p < 0,02). Já o CMI, tanto na braquial quanto na carótida, não foi significativo, independente do sexo: braquial em mulheres, 0,3 × 0,3 (p < 0,06); braquial em homens, 0,36 × 0,23 (p < 0,07); carótida em mulheres, 0,6 × 0,4 (p < 0,07); carótida em homens, 0,85 × 0,38 (p < 0,08). Utilizou-se como índice de significância p < 0,05. CONCLUSÃO: O DILA foi eficiente para atestar comprometimento endotelial em população de risco para aterosclerose

OBJECTIVE: To evaluate endothelial function in patients with risk factors for atherosclerosis by measuring brachial artery flow-mediated dilatation (BAFMD) and intima-media thickness (IMT) of carotid and brachial arteries. MATERIALS AND METHODS: A cross-sectional, case-control study in which endothelial function was evaluated by measurement of BAFMD and IMT of carotid and brachial arteries and presence or absence of risk factors in 112 patients distributed as follows: women with risk factors (n = 49), women control group (n = 24), men with risk factors (n = 21), men control group (n = 18). RESULTS: BAFMD was significantly compromised in the group with risk factors as compared with the control group, regardless of sex: in women, 15.2 × 25.3 (p < 0.01); in men, 11.8 × 16.8 (p < 0.02). On the other hand, IMT was not significant both for the carotid and brachial arteries, regardless of sex: brachial artery in women, 0.3 × 0.3 (p < 0.06); brachial artery in men, 0.36 × 0.23 (p < 0.07); carotid artery in women, 0.6 × 0.4 (p < 0.07); carotid artery in men, 0.85 × 0.38 (p < 0.08). The significance level was set at 5% (p < 0.05). CONCLUSION: Measurement of BAFMD was effective for detecting endothelial impairment in a population with risk factors for atherosclerosis

OBJETIVO: Medir o comprimento do colo uterino, utilizando a ultrassonografia transvaginal, em pacientes com quadro clínico compatível com ameaça de parto pré-termo, e correlacionar a medida do colo uterino, em cada caso, com a interrupção espontânea da gravidez dentro de sete dias. MATERIAIS E MÉTODOS: Foram realizados exames ultrassonográficos em 72 pacientes com quadro clínico compatível com ameaça de parto pré-termo. RESULTADOS: A sensibilidade do exame foi de 90,5%, a especificidade, de 98%, o valor preditivo positivo, de 95%, e o valor preditivo negativo, de 96%. A análise foi realizada utilizando-se a medida de 15 mm de comprimento do colo uterino como valor preditivo do parto pré-termo. CONCLUSÃO: Parece ser possível prever o parto pré-termo em pacientes com colo uterino menor que 15 mm. Tal observação poderá trazer contribuição para a administração mais oportuna de corticoides, com o intuito de acelerar a maturidade pulmonar fetal.

OBJECTIVE: To measure the uterine cervical length by using transvaginal ultrasonography in patients with clinical signs compatible with preterm labor threat, and correlating each individual measurement with spontaneous pregnancy interruption within seven days. MATERIALS AND METHODS: Sonographic examinations were performed in 72 patients with clinical signs compatible with preterm labor threat. RESULTS: Sensitivity was 90.5%, specificity, 98%, positive predictive value, 95%, and negative predictive value, 96%. A standard uterine cervix length of 15 mm was considered as a predictive value for preterm labor. CONCLUSION: It seems to be possible to foresee preterm delivery in patients whose cervical length is < 15 mm. Such observation could contribute to a timely corticosteroid administration to accelerate fetal lung maturity.

OBJETIVO: Avaliar a função endotelial em pacientes com artrite reumatóide, pela dilatação fluxo-mediada da artéria braquial. MATERIAIS E MÉTODOS: Sessenta e oito pacientes, sendo 32 com artrite reumatóide e 36 do grupo controle, foram avaliadas pela dilatação fluxo-mediada da artéria braquial (método ultra-sonográfico, no modo B, de avaliação de risco cardiovascular). Em um segundo tempo, foi avaliada a correlação entre a dilatação fluxo-mediada da artéria braquial, a proteína C reativa e o tempo de doença em pacientes com artrite reumatóide. RESULTADOS: A dilatação fluxo-mediada da artéria braquial na artrite reumatóide foi igual a 5,6 ± 9,69% e no grupo controle foi igual a 23,24 ± 5,65%, diferença estatisticamente significante (p < 0,00001). A proteína C-reativa teve resultado de 4,8 ± 9,1 mg/l. A correlação entre a idade, a dilatação fluxo-mediada da artéria braquial e a proteína C reativa nas pacientes com artrite reumatóide não mostrou resultado estatisticamente significante. CONCLUSÃO: Mulheres com artrite reumatóide apresentam importante disfunção endotelial quando comparadas com mulheres normais.

OBJECTIVE: To evaluate the endothelial function in patients with rheumatoid arthritis by means of brachial artery flow-mediated vasodilation. MATERIALS AND METHODS: Sixty-eight patients, 32 with rheumatoid arthritis and 36 in the control group, underwent brachial artery flow-mediated dilatation (B-mode ultrasound for evaluating cardiovascular risk). Afterwards, the correlation among brachial artery flow-mediated vasodilation, C-reactive protein, and disease duration in patients with rheumatoid arthritis was evaluated. RESULTS: The brachial artery flow-mediated dilatation of the brachial artery in rheumatoid arthritis corresponded to 5.6 ± 9.69%, and in the control group, to 23.24 ± 5.65%, with a statistically significant difference (p < 0.00001). C-reactive protein result was 4.8 ± 9.1 mg/l. The correlation among age, brachial artery flow-mediated dilatation, and C-reactive protein in patients with rheumatoid arthritis has not shown a statistically significant result. CONCLUSION: Women with rheumatoid arthritis present a significant endothelial dysfunction when compared with normal women.