Presentación inusual de coriocarcinoma metastásico a hígado y pulmón: un reporte de caso / Unusual presentation of metastatic choriocarcinoma to liver and lung: a case report

La enfermedad trofoblástica gestacional (ETG) es un trastorno proliferativo del trofoblasto. Incluye la mola hidatidiforme, el coriocarcinoma, la mola invasiva, el tumor trofoblástico del lecho placentario y el tumor trofoblástico epitelioide. Las últimas cuatro hacen parte de la neoplasia trofoblástica gestacional, que agrupa menos del 1% de todos los tumores ginecológicos. La incidencia de la ETG puede variar, siendo aproximadamente de 1 a 3 de cada 1.000 embarazos en América del Norte y Europa. El coriocarcinoma es la forma más agresiva por su rápida invasión vascular y compromiso metastásico. Sin embargo, es un tumor muy quimiosensible con una alta tasa de respuestas y posibilidad de curación superior al 90%. Se presenta el caso de una paciente de 40 años quien ingresó al servicio de urgencias por disnea súbita secundaria a tromboembolia pulmonar y posteriormente tras el inicio de anticoagulación presentó hemoperitoneo debido a lesiones hepáticas metastásicas de un coriocarcinoma, además de compromiso metastásico pulmonar. Se presenta este caso por ser una patología poco frecuente, agresiva y con presentaciones inusuales, con el fin de mostrar la importancia de un diagnóstico y tratamiento oportuno.

Gestational trophoblastic disease (GTD) is a condition in which the trophoblast, a layer of cells surrounding the embryo, develops abnormally. GTD includes both pre-malignant and malignant pathologies, such as hydatidiform mole, choriocarcinoma, invasive mole, placental site trophoblastic tumor, and epithelioid trophoblastic tumor. Although GTD is rare, it affects about 1 to 3 out of every 1,000 pregnancies in North America and Europe. Choriocarcinoma is the most aggressive form of GTD, as it can quickly invade blood vessels and metastasize to other parts of the body. However, it is highly responsive to chemotherapy, with a cure rate of over 90%. In this case, a 40-year-old patient presented to the emergency department with sudden dyspnea due to pulmonary embolism. After starting anticoagulation therapy, she developed hemoperitoneum due to the spread of choriocarcinoma to her liver, as well as pulmonary metastases. This case is noteworthy because of its unusual presentation and aggressive nature, underscoring the importance of early diagnosis and treatment.

Caracterización de enfermedad trofoblástica gestacional en el Hospital de Talca, 2013-2022 / Characterization of gestational trophoblastic disease at Hospital de Talca, 2013-2022

Introducción: La enfermedad trofoblástica gestacional (ETG) corresponde al espectro de lesiones proliferativas del tejido trofoblástico placentario. Presenta una incidencia mundial variable; en Chile no existen estudios nacionales, por lo que las cifras se deben extrapolar de estudios extranjeros. Objetivo: Caracterizar clínica y epidemiológicamente a las pacientes diagnosticadas con embarazo molar en el periodo 2013-2022 en el Hospital Regional de Talca (HRT). Método: Estudio observacional transversal, se consideró el recuento total de pacientes de la base de datos del Servicio de Onco-Ginecología (n = 100) y la cantidad de embarazos ocurridos entre 2013-2022 en el HRT. Resultados: La edad promedio de presentación fue de 32 años, obteniéndose una incidencia de ETG de 2,1 casos por cada 1.000 embarazos. El 54% de los casos corresponde a mola parcial. Los principales síntomas fueron metrorragia (67%) y dolor abdominal (40%). El principal tratamiento efectuado fue aspiración uterina (92%). En el 48% de los casos se sospechó la ETG con la clínica previo al diagnóstico por biopsia y solo en un 13% únicamente con estudio ecográfico. Conclusiones: Es necesario realizar más investigaciones nacionales que permitan recopilar información actualizada sobre ETG, sobre todo por la variabilidad clínica de la enfermedad, que hace difícil su sospecha diagnóstica.

Introduction: Gestational trophoblastic disease (GTO) corresponds to the spectrum of proliferative lesions of placental trophoblastic tissue. It has a variable global incidence; in Chile there are no national studies so it must be extrapolated from foreign studies. Objective: To clinically and epidemiologically characterize patients diagnosed with molar pregnancy in the period 2013-2022, at the Talca Regional Hospital (HRT). Method: Cross-sectional observational study, the total count of patients from the Onco-Gynecology Service database (n = 100) and the number of pregnancies that occurred between 2013-2022 in the HRT were considered. Results: The average age of presentation was 32 years, obtaining an incidence of GTO of 2.1 cases per 1000 pregnancies; 54% of cases correspond to partial mole. The main symptoms were metrorrhagia (67%) and abdominal pain (40%). The main treatment performed was uterine aspiration (92%). In 48% of the cases, GTO was suspected with clinical symptoms prior to diagnosis by biopsy, and only 13% with an ultrasound study alone. Conclusions: It is necessary to carry out more national research to collect updated information on GTO, especially due to the clinical variability of the disease that makes its diagnostic suspicion difficult.

Correlation of uterine artery Doppler flow velocimetry and β-human chorionic gonadotropin levels during postmolar evacuation surveillance: A pilot study in a tertiary hospital / Philippine Journal of Obstetrics and Gynecology

Background@#During postmolar evacuation surveillance, beta-human chorionic gonadotropin (β-hCG) regression levels can predict invasive disease while Doppler ultrasound can assess in vivo tumor neovascularization and quantify uterine blood supply. As an ancillary tool to β-hCG monitoring, ultrasound can detect the early presence of viable trophoblastic tissues and identify patients at risk of developing postmolar gestational trophoblastic Neoplasia (PMGTN). @*Objective@#The objective of this study was to correlate uterine artery Doppler ultrasound with β-hCG levels during pre- and postmolar evacuation surveillance among patients with complete mole.@*Materials and Methods@#A cohort of patients with sonographic diagnosis of complete hydatidiform mole and managed with suction curettage in the same institution were prospectively followed up after evacuation. The pre- and postmolar evacuation surveillance period was at days 1, 7, 14, 21, 28, and 35. Monitoring of serum β-hCG levels was based on the standard regression curve. For Doppler ultrasound parameters, monitoring of the systolic/diastolic (S/D) ratio, pulsatility index (PI), resistance index (RI), and peak systolic velocity (PSV) was based on its relationship with its serum β-hCG levels. The ultrasound images generated were archived and reviewed by the authors. Descriptive and inferential statistics were utilized to analyze median differences. For the correlation of uterine artery Doppler flow parameters, analysis for the test of difference used Pearson correlation and multiple linear regression analysis for the odds ratio.@*Results@#Sixteen of the 23 enrolled patients completed the protocol (16 of 23, 69.50%). A majority had spontaneous remission (13; 81%) while 3 cases (19%) presented increasing and plateauing β-hCG levels. The pre- and post evacuation median β-hCG levels showed a significant decrease (P = 0.001). As post evacuation β-hCG levels decreased, PSV also decreased (r = 0.478, P = 0.061) while Doppler parameters, RI, PI, and S/D ratio increased. However, when post evacuation β-hCG levels rose or plateaued, Doppler parameters decreased. These changes had statistical correlation (all P < 0.05). Moreover, the magnitude of the relationship for β-hCG and Doppler parameters was moderate and ranged from 0.524 to 0.581. Among the Doppler parameters, the S/D ratio and RI of the right uterine artery strongly predicted a rise in β-hCG levels. The odds ratio of predicting increased β-hCG levels and risk of gestational trophoblastic neoplasia by the right S/D ratio were − 2683.67 (confidence interval [CI] = −271.692–5095.655; P = 0.034) and by the right RI − 66,193.34 (CI = −161,818.107–29,431.433; P = 0.046). Notably, Doppler parameter changes appeared early at day 14 up to day 35 and before the appearance of abnormal β-hCG regression patterns.@*Conclusion@#There is a strong correlation between uterine artery Doppler flow changes and β-hCG levels during postmolar evacuation surveillance. The inverse relationship of the S/D ratio, PI and RI, and β-hCG regression patterns confirms spontaneous remission of the disease. For patients with abnormal β-hCG patterns, this relationship is altered. The Doppler changes become erratic, unpredictable, and significantly decreased. These changes were detected as early as 2 weeks post evacuation. Thus, the use of ultrasound as an adjunct to β-hCG post evacuation surveillance can predict abnormal β-hCG regression patterns and identify patients at risk of developing postmolar gestational trophoblastic neoplasia (PMGTN).

Choriocarcinoma presenting as late postpartum hemorrhage in a 21-year-old primipara / Philippine Journal of Obstetrics and Gynecology

Introduction@#Obstetrical hemorrhage remains to be one of the most common causes of maternal morbidity and mortality. Postpartum hemorrhage occurs after delivery and is usually secondary to uterine atony, genital tract lacerations, and retained placental fragments.@*Case@#A case of a 21-year old, primipara, presented with profuse vaginal bleeding and hemoptysis at 3 weeks' postpartum. A clinical diagnosis of gestational trophoblastic neoplasia was established after an elevated serum beta human chorionic gonadotropin was obtained and an intrauterine mass was seen on ultrasonography, including metastasis to the lungs and liver seen through imaging studies.@*Discussion@#Chemotherapy with etoposide, methotrexate, actinomycin D, cyclophosphamide and oncovin (EMACO) is the mainstay treatment for Stage IV disease. However, complications such as hemorrhage and tumor rupture are best managed surgically. Although rare, a diagnosis of choriocarcinoma should be considered in patients with persistent bleeding after a normal pregnancy to institute proper management and avoid associated complications of tumor progression.

The effects of induction chemotherapy in the management of ultra high-risk gestational trophoblastic neoplasia

Objectives@#This study aimed to determine the clinical outcomes of ultra high-risk gestational trophoblastic neoplasia (GTN) patients managed with and without induction chemotherapy in the Division of Trophoblastic Diseases, Department of Obstetrics and Gynecology, Philippine General Hospital.@*Methods@#Clinical and demographic data were collected retrospectively from ultra high-risk GTN patients admitted in the Division of Trophoblastic Diseases, Department of Obstetrics and Gynecology, Philippine General Hospital from January 2015 to December 2021. Rate of remission and early death of those who received induction chemotherapy were compared to those who did not.@*Results@#A total of 21 patients with ultra high-risk GTN were included in the study, nine of whom underwent induction chemotherapy while 12 had no induction chemotherapy and was given the standard EMACO regimen. There was no significant difference in the rate of early death as well as the rate and time to achieve remission between those who received induction chemotherapy compared to those who were immediately started on EMACO.@*Conclusion@#A firm conclusion cannot be drawn from the results considering the small population included in the study. Further studies with larger sample size and prospective study design are recommended.

Chemo-resistant gestational trophoblastic neoplasia and the use of immunotherapy: A case report and review of literature

@#This is the first reported case of the use of immunotherapy in chemo-resistant Gestational Trophoblastic Neoplasia (GTN) in the country. A 41-year-old, Gravida 4 Para 3 (3013) with a diagnosis of GTN, Stage III: WHO risk score of 13 (Choriocarcinoma) was initially managed with 10 cycles of multiple agent Etoposide, Methotrexate, Actinomycin D- Cyclophosphomide and Vincristine (EMACO) and 19 cycles of Etoposide, Cisplatin- Etoposide Methotrexate and Actinomycin D (EP-EMA). With continuous rise in beta human chorionic gonadotropin (ßhCG) levels, the patient was referred to a Trophoblastic Disease Center where there was note of tumor progression to the brain. She was started on third-line salvage chemotherapy of Paclitaxel and Carboplatin (PC) with concomitant whole brain irradiation completing three cycles after which chemoresistance was again diagnosed with increasing hCG titers and increase in the number and size of the pulmonary masses which were deemed unresectable. Immunotherapy was started with Pembrolizumab showing a good response with marked fall in ßhCG levels. The onset of immune-related adverse events (irAEs) caused a marked delay in subsequent cycles of immunotherapy. With management of the irAEs, two more cycles of Pembrolizumab with fifty percent dose reduction were given with corresponding drop in ßhCG levels. However, the patient subsequently developed gram-negative septicemia with possible hematologic malignancy and finally succumbed to massive pulmonary embolism. The case highlights the importance of prompt diagnosis and referral to a Trophoblastic Disease Center and the use of immunotherapy in chemo-resistant GTN.

Geographical Health District and Distance Traveled Influence on Clinical Status at Admission of Patients with Gestational Trophoblastic Disease / A influência do distrito de saúde e da distância viajada sobre o estado clínico na apresentação de pacientes com doença trofoblástica gestacional

Abstract Objective To assess the potential relationship of clinical status upon admission and distance traveled from geographical health district in women with gestational trophoblastic disease (GTD). Methods This is a cross-sectional study including women with GTD from the 17 health districts from the São Paulo state (I-XVII), Brazil, referred to the Botucatu Trophoblastic Disease Center (specialized center, district VI), between 1990 and 2018. At admission, hydatidiform mole was assessed according to the risk score system of Berkowitz et al. Gestational trophoblastic neoplasia was evaluated using the International Federation of Gynecology and Obstetrics / World Health Organization (FIGO/WHO) staging/risk score. Data on demographics, clinical status and distance traveled were collected. Multiple regression analyses were performed. Results This study included 366 women (335 hydatidiform mole, 31 gestational trophoblastic neoplasia). The clinical status at admission and distance traveled significantly differed between the specialized center district and other districts. Patients referred from health districts IX (β = 2.38 [0.87-3.88], p = 0.002) and XVI (β = 0.78 [0.02-1.55], p = 0.045) had higher hydatidiform mole scores than those from the specialized center district. Gestational trophoblastic neoplasia patients from district XVI showed a 3.32 increase in FIGO risk scores compared with those from the specialized center area (β = 3.32, 95% CI = 0.78-5.87, p = 0.010). Distance traveled by patients from districts IX (200km) and XVI (203.5km) was significantly longer than that traveled by patients from the specialized center district (76km). Conclusion Patients from health districts outside the specialized center area had higher risk scores for both hydatidiform mole and gestational trophoblastic neoplasia at admission. Long distances (>80 km) seemed to adversely influence gestational trophoblastic disease clinical status at admission, indicating barriers to accessing specialized centers.

Resumo Objetivo Avaliar a possível relação entre estado clínico na apresentação e distância percorrida a partir do distrito de saúde em mulheres com doença trofoblástica gestacional. Métodos Estudo transversal incluindo mulheres com doença trofoblástica gestacional dos 17 distritos de saúde do estado de São Paulo (I-XVII), Brasil, encaminhadas ao Centro de Doenças Trofoblásticas de Botucatu (distrito VI), entre 1990 e 2018. Na admissão, avaliaram-se mola hidatiforme pelo sistema de pontuação de risco de Berkowitz et al. e neoplasia trofoblástica gestacional pelo escore de risco/estadiamento Federação Internacional de Ginecologia e Obstetrícia / Organização Mundial da Saúde (FIGO/OMS). Coletaram-se dados demográficos, clínicos e distância percorrida e análises de regressão múltipla foram realizadas. Resultados Este estudo incluiu 366 mulheres (335 mola hidatiforme, 31 neoplasia trofoblástica gestacional). O estado clínico na apresentação e distância percorrida diferiram significativamente entre o centro especializado e demais distritos. Nas pacientes encaminhadas pelos distritos IX (β = 2,38 [0,87-3,88], p = 0,002) e XVI (β = 0,78 [0,02-1,55], p = 0,045), os escores de mola hidatiforme foram maiores que no centro especializado. As pacientes com neoplasia trofoblástica gestacional do distrito XVI apresentaram escores FIGO 3,32 vezes maior que no centro especializado (β = 3,32, 95% CI = 0,78-5,87, p = 0,010). A distância percorrida pelas pacientes dos distritos IX (200km) e XVI (203,5km) foi significativamente maior do que a percorrida pelas pacientes do centro especializado (76km). Conclusão Pacientes de distritos de saúde fora da cobertura do centro especializado apresentaram escores de risco mais alto para mola hidatiforme e para neoplasia trofoblástica gestacional na admissão. Longas distâncias (>80 km) pareceram influenciar negativamente o estado clínico da doença trofoblástica gestacional na apresentação, indicando barreiras no acesso a centros especializados.

Acesso a um serviço de saúde público especializado: experiência no centro de referência de doença trofoblástica gestacional do Hospital São Paulo / Accessing a specialized public health service: the São Paulo Hospital reference center for gestational trophoblastic diseases

Objetivo: Analisar a trajetória das mulheres com doença trofoblástica gestacional (DTG) até o Centro de Referência de Doença Trofoblástica Gestacional do Hospital São Paulo (CRDTG-HSP), identificando as portas de entrada ao serviço e as dificuldades que elas enfrentaram desde o diagnóstico. Métodos: Estudo de caso transversal exploratório, descritivo-analítico, com abordagem quali-quantitativa, que incluiu pacientes atendidas no período de 2015 a 2018. A coleta dos dados se deu por meio de um questionário on-line e de uma entrevista com roteiro semiestruturado. Resultados: Entre 96 pacientes, 40,63% (n = 39) tiveram acesso ao CRDTG-HSP por encaminhamento entre médicos, 31,25% (n = 30), pela página do Facebook da Associação Brasileira de Doença Trofoblástica Gestacional e 10,42% (n = 10), por meio da central de regulação de vagas do estado de São Paulo (CROSS), das quais 28,2%, 73% e 30%, respectivamente, possuíam assistência privada, na qual receberam tratamento inicial. As 12 entrevistadas relataram dificuldades, tais como a percepção da falta de preparo médico no manejo e comunicação da doença, o desconhecimento da sua situação de saúde mesmo após procedimentos cirúrgicos, a exposição a conversas inapropriadas entre médicos sobre o seu caso e o recebimento de encaminhamento sem explicação esclarecedora sobre seu quadro clínico. Por fim, as pacientes avaliaram positivamente a utilização de e-mail e WhatsApp como facilitadores no atendimento no CRDTG-HSP. Conclusão: O acesso ao CRDTG-HSP ocorreu minoritariamente pela CROSS e, mesmo tendo assistência privada, pacientes migraram para atendimento no centro especializado. Além disso, as pacientes tiveram percepção de falta de preparo médico no atendimento da DTG fora do CRDTG.(AU)

Objective: To understand and elaborate the trajectories of women with gestational trophoblastic disease from the initial entry to the healthcare system to follow-up at a public tertiary reference center. Methods: This exploratory, descriptive-analytical, cross-sectional case study included patients from 2015 to 2018. The data collected through online questionnaires and semi-structured interviews were analyzed via quantitative and qualitative approaches. Statistical analysis was performed using Pearson's chi-square test at 5% significance using software R version 4.0.2. The test power for the sample was calculated using G*power software version 3.1.9.6. Results: Overall, 96 patients completed the questionnaire. Only 10(10.42%) patients reached the reference center through the official channel, Sao Paulo State Vacancy Regulation Center, while 39(40.63%) patients through referral from physicians, and 30(31.25%) patients through the Brazilian Association of Gestational Trophoblastic Disease's Facebook fan page. Overall, 36 patients (37.5%) had private insurance and 73% of patients who reached the reference center via Facebook had private insurance. Twelve participants were interviewed and reported barriers, such as difficulties in understanding their health issues prior to arrival at the reference center, lack of professional knowledge about the disease, poor communication, and exposure to inappropriate conversations. They positively evaluated the reference center, the interaction was facilitated using email and WhatsApp. Conclusion: Although appropriate public care for these women exists, the flow from the diagnosis to specialized treatment remains unclear for both professionals and patients. The participants perceived that communication and physicians' expertise were inadequate.(AU)

Precision medicine in gestational trophoblastic disease / Philippine Journal of Obstetrics and Gynecology

@#Precision medicine is a form of medicine that utilizes information about a person’s own genes to prevent, diagnose, or treat disease. In trophoblastic disease, precision medicine is important for accurate diagnosis, risk stratification, prognostication, and management. Immunohistochemistry, particularly p57kip2, has become an important ancillary procedure for the accurate identification of complete hydatidiform mole (HM). Molecular genotyping, on the other hand, is now considered the gold standard for the accurate classification of HM. Both tests are important for prognostication and the determination of the appropriate follow‑up plan. For gestational trophoblastic neoplasia, immunohistochemical markers can confirm the histologic diagnosis of its various types. Molecular genotyping differentiates gestational from nongestational tumors with overlapping histology and allows for precise identification of the index or causative pregnancy of a choriocarcinoma.

Comparison of beta‑human chorionic gonadotropin‑based prognostic models on the clinical outcomes of gestational trophoblastic disease patients in the Philippines / Philippine Journal of Obstetrics and Gynecology

Objective@#Despite the widespread use and measurement of beta‑human chorionic gonadotropin (β‑HCG) among hydatidiform mole (HM) patients, models derived from this biomarker to predict the remission or postmolar gestational trophoblastic neoplasia (GTN) rarely perform well. The study aimed to generate cutoff points for postevacuation β‑HCG levels and evaluate their performance among women with complete molar pregnancies@*Methods@#A retrospective cohort study composed of women with complete HM underwent bivariate procedures comparing characteristics between the comparison groups. Cut points using Liu’s and Youden’s indices were estimated, and their performance was evaluated using receiver operating characteristic curve analysis. Cox regression to compare time‑to‑progression across these proposed β‑HCG cutoffs was also performed.@*Results@#The incidence of postmolar GTN among the 155 women in the study was 15.5% (95% confidence interval: 10.2%–22.2%). Postevacuation HCG levels had a better prediction of disease status than preevacuation and HCG ratio models (χ2 : 163.07, P < 0.01). A cutoff at 508 mIU/mL the 3rd‑week postevacuation (area under the curve [AUC]: 0.89, sensitivity: 87.5%, specificity: 90.1%) was comparable with the 185 mIU/mL cutoff at the 5th‑week postevacuation (AUC: 0.89, sensitivity: 91.7%, specificity: 87%). The hazards ratio of postmolar GTN was 29.74 (8.53–103.71) and 39.89 (8.82–180.38) for the 3rd and 5th weeks HCG after evacuation adjusting for clinically relevant variables@*Conclusion@#The first 3rd‑ and 5th‑week postevacuation levels of β‑HCG demonstrated potential in predicting postmolar GTN. However, further refinement and adjustment for clinically relevant risk factors are still needed.

The use of uterine artery Doppler studies as predictors for postmolar gestational trophoblastic neoplasia / Philippine Journal of Obstetrics and Gynecology

Background@#Gestational trophoblastic neoplasia (GTN) is considered one of the most curable malignancies, especially when diagnosis and treatment are commenced early. Identifying predictors for the development of GTN will enable prompt management equating to an excellent prognosis.@*Objectives@#The objectives of this study were to determine the validity of uterine artery Doppler parameters (UADPs) as predictors for postmolar GTN, compare UADP values before and after evacuation, determine cutoff values and relationship with beta‑human chorionic gonadotropin (hCG) levels.@*Materials and methods@#This was a prospective cohort study, which included histopathologically confirmed hydatidiform mole (HM) patients who underwent suction curettage. UADPs (pulsatility index (PI), resistive index, and systolic/diastolic [S/D] ratio) were measured preevacuation, 4 weeks postevacuation, and 6 weeks postevacuation. Patients were followed up to determine whether they will develop postmolar GTN or not.@*Results@#A total of 31 HM patients were admitted during the study period, 84% (26/31) of whom underwent suction curettage. Of these, 92% (24/26) had histopathology of complete HM and were recruited. However, only 17 patients followed up and completed the study. Results showed that there was an increasing trend of the UADP from preevacuation to 6 weeks postevacuation and the trend between those with and without postmolar GTN was statistically significant. There was also an inverse relationship between the UADP and baseline β‑hCG values. UADP showed lower values among patients who developed postmolar GTN compared to those who did not. The cutoff values recommended by the area under curve (AUC) that can be a possible predictor were 4th‑week right PI of 2.14 (AUC = 0.71) and right S/D ratio of 2.60 (AUC = 0.73) and 6th‑week left PI of 2.80 (AUC = 0.70) and right PI of 2.53 (AUC = 0.74).@*Conclusion@#Neoangiogenesis, a hallmark of malignancy, is correlated with invasive disease and will show increased myometrial vascularization with lower uterine artery indices. Doppler ultrasound may be a useful tool for postmolar follow‑up and GTN diagnosis. However, the small sample size in this study is a limitation and a larger multicenter study is recommended.

Association of ultrasound morphological features with serum β subunit human chorionic gonadotrophin and histopathology among sonologically diagnosed cases of gestational trophoblastic neoplasia in a tertiary hospital / Philippine Journal of Obstetrics and Gynecology

Background@#Gestational trophoblastic neoplasia (GTN) presents as vascular mass of varying morphology on ultrasound and confirmed through quantitative serum β subunit human chorionic gonadotrophin (β‑hCG). In regions with limited access to β‑hCG, ultrasound plays a crucial role in the initial diagnosis for timely management.@*Objectives@#This study aimed to investigate the associations between ultrasound vascular morphologic features, serum β‑hCG levels, and histopathology in GTN cases.@*Methodology@#A cross‑sectional review was conducted on 113 cases with ultrasound impression of GTN over an 8‑year period. The patient data were extracted from case records, and ultrasound images were categorized based on the distinct features. Associations with β‑hCG levels and histopathology were analyzed using the Chi‑square test and Mann–Whitney U‑test. Statistical significance was set at P < 0.05.@*Results@#A significant association was observed between ultrasound category and serum β‑hCG (P < 0.0001). The compact and diffuse types were more prevalent with β‑hCG levels between 104 to <105 mIU/mL, while the lacunar type was common among patients with ≥105 mIU/mL. However, there was no significant association between ultrasound categories and mean β‑hCG levels. Regarding histopathology, the lacunar type was more common in invasive moles, whereas the compact and diffuse types tended to be seen with choriocarcinoma, although these were not statistically significant (P = 0.182).@*Conclusions@#Morphologic types of GTN by gray scale and Doppler ultrasound vary across the different levels of serum β‑hCG and may suggest the histopathological diagnosis. This study provides valuable insights into the ultrasonographic characteristics of GTN, which can aid in its diagnosis and management.

Bizarre presentation of choriocarcinoma: A case report / Philippine Journal of Obstetrics and Gynecology

@#Choriocarcinoma is a malignant subtype of gestational trophoblastic disease that follows any type of pregnancy. It is characterized by rapid hematogenous spread to multiple organs, associated with high human chorionic gonadotropin levels with good response to chemotherapy. We present the case of a 31‑year‑old Filipina who initially presented with severe headaches and blurring of vision 3 years after an unremarkable term pregnancy. The transvaginal ultrasound was normal. After a series of diagnostic tests, the initial working impression was a primary brain tumor with metastases to the lungs, adrenal, kidney, and vulva. Emergency craniotomy was done due to deteriorating status secondary to an intracranial hemorrhage. The histopathology report showed choriocarcinoma. Chemotherapy using Etoposide‑Methotrexate‑Actinomycin D‑Cyclophosphamide‑Vincristine with high‑dose methotrexate and concomitant whole‑brain irradiation was then instituted with good response. This case highlights the importance of having a high index of suspicion for gestational trophoblastic neoplasia to prevent the performance of unnecessary procedures, leading to a delay in diagnosis and the institution of the appropriate treatment.

Gestational trophoblastic neoplasia coexisting with cervical carcinoma: A case report / Philippine Journal of Obstetrics and Gynecology

@#Gestational trophoblastic neoplasia (GTN) with a concurrent cervical malignancy is very rare, making the case both a diagnostic dilemma and a therapeutic challenge. Currently, there has only been one reported case worldwide. We present a case of GTN Stage I:11 with non‑keratinizing squamous cell carcinoma of the cervix Stage II‑B. Initial treatment, in the form of chemotherapy, was directed toward the GTN, as this appeared to be the more aggressive disease. Surgery was not feasible during diagnosis due to the cervical carcinoma. However, the GTN proved resistant to chemotherapy due to the increasing beta human chorionic gonadotropin titers. An attempt to decrease the size of the cervix for surgery to be possible through chemoradiation was instituted, but due to complications and tumor progression to the lungs, she succumbed to the malignancy.

Exaggerated placental site gestational trophoblastic disease: A case report / Philippine Journal of Obstetrics and Gynecology

@#Gestational trophoblastic diseases (GTDs) represent a unique group of lesions with an abnormal proliferation of trophoblasts. GTD can be divided into molar lesions and nonmolar lesions. Partial and complete hydatidiform moles and invasive moles are under molar lesions, whereas non‑molar lesions include choriocarcinomas and lesions that are derived from intermediate trophoblasts (ITs). These IT can be from the implantation site (exaggerated placental site [EPS] and placental site trophoblastic tumor) or from the chorionic type (placental site nodule and epithelioid trophoblastic tumor). EPS is a relatively uncommon form of GTD. It is a challenging condition for clinicians to diagnose because of the limited number of reported cases. From 1990 to April 2022, there were only 25 case reports published internationally, and this is the first local case report. Implantation site ITs (ISITs) are difficult to distinguish histologically. Immunohistochemical staining such as Ki‑67 can improve diagnostic accuracy by differentiating ISIT. Ki 67 will show staining of <1% in EPS. This is the case of a 25‑year‑old patient, G6P5 (5005), who experienced vaginal bleeding associated with pelvic and hypogastric pain after 13 weeks of missed menses. She was diagnosed with a molar pregnancy and underwent an emergency total abdominal hysterectomy with bilateral salpingectomy due to severe uterine bleeding. Histopathologic studies in this case showed diffuse and infiltrative growth of atypical monomorphic ITs arranged in sheets and cords, infiltrating and separating myometrial fibers. The uterine blood vessel wall was replaced with fibrinoid deposition, with areas of hemorrhages and necrosis. There were also chorionic villi. The histopathological findings revealed GTD arising from ITs, specifically EPS. This article describes the clinical presentation, diagnostic procedure, and management, together with histopathological observations and a review of related literature, of this rare GTD.

Metastatic placental site trophoblastic tumor with pelvic arteriovenous malformation: A case report / Philippine Journal of Obstetrics and Gynecology

@#Placental site trophoblastic tumor (PSTT) with uterine arteriovenous malformation (AVM) is a rare and potentially catastrophic occurrence. A high index of suspicion and immunohistochemistry secured the diagnosis. The use of appropriate imaging modalities led to the identification of the extent of the disease. Sequential planned management from neoadjuvant intensive chemotherapy, bilateral uterine artery embolization, and laparotomy, and coordinated among different medical disciplines resulted to a successful definitive treatment. Due to its relatively chemoresistant nature, hysterectomy is the mainstay of treatment. Adjuvant platinum-based intensive chemotherapy has been shown to improve overall survival in patients with metastatic disease and those with poor prognostic factors. This case of PSTT with a typical clinical profile was noteworthy due to the development of a significant AVM, a rare complication of PSTT. This case report included a review of treatment experiences as well as peculiarities that set PSTT apart from the more common gestational trophoblastic diseases.

O papel da ultrassonografia na doença trofoblástica gestacional / The role of ultrasonography in gestational trophoblastic disease

A doença trofoblástica gestacional (DTG) agrupa um conjunto de anomalias do desenvolvimento trofoblástico, que incluem formas clínicas benignas como a mola hidatiforme completa e parcial, o nódulo do sítio placentário atípico e o sítio trofoblástico exagerado, e malignas, caracterizando a neoplasia trofoblástica gestacional (NTG). De modo geral, seu diagnóstico precoce antecipa complicações clínicas que podem estar associadas a near miss obstétrico. Diante da suspeição clínica, é a ultrassonografia (US) precoce o exame de escolha pa ra o diagnóstico, associado à dosagem sérica de gonadotrofina coriônica humana, capaz de minimizar a ocorrência de complicações clínicas associadas à gravidez molar. Nos casos de NTG, é a US também de grande valia para estadiamento, avaliação de prognóstico e acompanhamento da mulher tratada para DTG. Este estudo faz uma revisão sobre o papel da US na DTG, sendo importante para familiarizar os tocoginecologistas com essa doença e salientar o papel da US consoante as melhores práticas clínicas.(AU)

Gestational trophoblastic disease (GTD) includes a set of trophoblastic developmental anomalies, which include benign forms such as complete and partial hydatidiform mole, atypical placental site nodule and exaggerated trophoblastic site, and malignant forms, characterizing gestational trophoblastic neoplasia (GTN). In general, its early diagnosis anticipates clinical complications that could be associated with obstetric near miss. In view of clinical suspicion, early ultrasonography (US) and serum levels of human chorionic gonadotropin are the best diagnostic screening techniques, able to minimizing the occurrence of medical complications associated with molar pregnancy. In cases of GTN, US is also of great value for staging, assessment of prognosis and follow-up of women treated for GTN. This study reviews the role of US in GTD, being important to familiarize tocogynecologists with this disease and highlight the role of US according to best clinical practices to minimize the morbidity of these patients and maximize the remission rates of this disease.(AU)

Clinical Presentation, Treatment Outcomes, and Resistance-related Factors in South American Women with Low-risk Postmolar Gestational Trophoblastic Neoplasia / Apresentação clínica, resultados do tratamento e fatores relacionados à resistência em mulheres sul-americanas com neoplasia trofoblástica gestacional pós-molar de baixo risco

Abstract Objective There are few multinational studies on gestational trophoblastic neoplasia (GTN) treatment outcomes in South America. The purpose of this study was to assess the clinical presentation, treatment outcomes, and factors associated with chemoresistance in low-risk postmolar GTN treated with first-line single-agent chemotherapy in three South American centers. Methods Multicentric, historical cohort study including women with International Federation of Gynecology and Obstetrics (FIGO)-staged low-risk postmolar GTN attending centers in Argentina, Brazil, and Colombia between 1990 and 2014. Data were obtained on patient characteristics, disease presentation, and treatment response. Logistic regression was used to assess the relationship between clinical factors and resistance to first-line single-agent treatment. A multivariate analysis of the clinical factors significant in univariate analysis was performed. Results A total of 163 women with low-risk GTN were included in the analysis. The overall rate of complete response to first-line chemotherapy was 80% (130/163). The rates of complete response to methotrexate or actinomycin-D as first-line treatment, and actinomycin-D as second-line treatment postmethotrexate failure were 79% (125/157), 83% (⅚), and 70% (23/33), respectively. Switching to second-line treatment due to chemoresistance occurred in 20.2% of cases (33/163). The multivariate analysis demonstrated that patients with a 5 to 6 FIGO risk score were 4.2-fold more likely to develop resistance to first-line single-agent treatment (p= 0.019). Conclusion 1) At presentation, most women showed clinical characteristics favorable to a good outcome, 2) the overall rate of sustained complete remission after first-line single-agent treatment was comparable to that observed in developed countries, 3) a FIGO risk score of 5 or 6 is associated with development of resistance to first-line single-agent chemotherapy.

Resumo Objetivo Existem poucos estudos multinacionais sobre os resultados do tratamento da neoplasia trofoblástica gestacional (NTG) na América do Sul. O objetivo deste estudo foi avaliar a apresentação clínica, os resultados do tratamento e os fatores associados a casos de quimiorresistência em NTG pós-molar de baixo risco tratados com quimioterapia de agente único de primeira linha em três centros sul-americanos. Métodos Estudo multicêntrico de coorte histórica incluindo mulheres com NTG pós-molar de baixo risco com estadiamento International Federation of Gynecology and Obstetrics (FIGO) em centros de atendimento na Argentina, Brasil e Colômbia entre 1990 e 2014. Foram obtidos dados sobre as características do paciente, apresentação da doença e resposta ao tratamento. A regressão logística foi usada para avaliar a relação entre fatores clínicos e resistência ao tratamento de primeira linha com agente único. Foi realizada uma análise multivariada dos fatores clínicos significativos na análise univariada. Resultados Cento e sessenta e três mulheres com NTG de baixo risco foram incluídas na análise. A taxa global de resposta completa à quimioterapia de primeira linha foi de 80% (130/163). As taxas de resposta completa ao metotrexato ou actinomicina-D como tratamento de primeira linha e actinomicina-D como tratamento de segunda linha após falha do metotrexato foram 79% (125/157), 83% (⅚) e 70% (23/33), respectivamente. A mudança para o tratamento de segunda linha por quimiorresistência ocorreu em 20,2% dos casos (33/163). A análise multivariada demonstrou que pacientes com pontuação de risco FIGO de 5 a 6 foram 4,2 vezes mais propensos a desenvolver resistência ao tratamento com agente único de primeira linha (p= 0,019). Conclusão 1) Na apresentação, a maioria das mulheres demonstrou características clínicas favoráveis a um bom resultado, 2) a taxa geral de remissão completa sustentada após o tratamento de primeira linha com agente único foi comparável à de países desenvolvidos, 3) um escore de risco FIGO de 5 ou 6 está associado ao desenvolvimento de resistência à quimioterapia de agente único de primeira linha.

Emotional and Clinical Aspects Observed in Women with Gestational Trophoblastic Disease: A Multidisciplinary Action / Aspectos emocionais e clínicos observados em mulheres com doença trofoblástica gestacional: Uma ação multidisciplinar

Abstract Objective To evaluate the emotional and clinical aspects observed in women with gestational trophoblastic disease (GTD) followed-up in a reference center (RC) by a multidisciplinary team. Methods Retrospective cohort study of the clinical records of 186 women with GTD and of the emotional aspects (EA) observed in these women by a teamof psychologists and reported by the 389 support groups conducted from 2014 to 2018. Results The women were young (mean age: 31.2 years), 47% had no living child, 60% had planned the pregnancy, and 50% participated in two or more SG. Most women (n=137; 73.6%) reached spontaneous remission ofmolar gestation in a median time of 10 weeks and had a total follow-up time of seven months. In the group of 49 women (26.3%) who progressed to gestational trophoblastic neoplasia (GTN), time to remission after chemotherapy was 18 weeks, and total follow-up time was 36 months. EA included different levels of anxiety and depression,more evident in 9.1% of the women; these symptoms tended to occur more frequently in women older than 40 years (p=0.067), less educated (p=0.054), and whose disease progressed to GTN (p=0.018), as well as in those who had to undergo multi-agent chemotherapy (p=0.028) or hysterectomy (p=0.001) adjuvant to clinical treatment. Conclusion This study found several EA in association with all types of GTD. It also highlights the importance of specialized care only found in a RC, essential to support the recovery of the mental health of these women.

Resumo Objetivo Avaliar aspectos emocionais e clínicos observados em mulheres com doença trofoblástica gestacional (DTG) acompanhadas em um centro de referência (CR), por equipe multiprofissional. Método Estudo de coorte retrospectivo nos prontuários clínicos de 186 mulheres comDTG, e dos aspectos emocionais (AE) observados nessas mulheres pela equipe de psicólogas e registrados nos 389 grupos de apoio (GAs), ocorridos de 2014 a 2018. Resultados As pacientes eram jovens (idade média 31,2 anos), 47% sem filhos vivos, 60% tinham desejado ou planejado esta gravidez e 50% delas participaram de dois ou mais GAs. A maioria (n=137-73,6%) apresentou remissão espontânea da gestação molar com mediana de 10 semanas e um tempo total de seguimento de 7 meses. Quarenta e nove mulheres (26,3%) evoluíram para neoplasia trofoblástica gestacional (NTG); amediana para atingir a remissão após tratamento comquimioterapia foi de 19 semanas e o tempo total de seguimento foi de 36 meses. Os AE incluíram variados graus de ansiedade e depressão, mais evidentes em 9,1% das nossas pacientes; tais AE tenderam a ocorrer mais em mulheres com idade acima de 40 anos (p=0,067), com menor escolaridade (p=0,054), com evolução para NTG (p=0,018), e nas que necessitaram de tratamento quimioterápico com regime de múltiplos agentes (p=0,028), ou de histerectomia complementar ao tratamento clínico (p=0,001). Conclusão Este estudo mostrou presença de vários AE associados em todos os tipos de DTG. Destaca tambéma importância de umatendimento psicológico especializado, somente encontrado nos CR, que é essencial para ajudar na recuperação da saúde mental dessas mulheres.

Evaluation and simplification of risk factors in FIGO 2000 scoring system for gestational trophoblastic neoplasia: a 19-year retrospective analysis / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

OBJECTIVES@#The International Federation of Gynecology and Obstetrics (FIGO) 2000 scoring system classifies gestational trophoblastic neoplasia (GTN) patients into low- and high-risk groups, so that single- or multi-agent chemotherapy can be administered accordingly. However, a number of FIGO-defined low-risk patients still exhibit resistance to single-agent regimens, and the risk factors currently adopted in the FIGO scoring system possess inequable values for predicting single-agent chemoresistance. The purpose of this study is therefore to evaluate the efficacy of risk factors in predicting single-agent chemoresistance and explore the feasibility of simplifying the FIGO 2000 scoring system for GTN.@*METHODS@#The clinical data of 578 GTN patients who received chemotherapy between January 2000 and December 2018 were retrospectively reviewed. Univariate and multivariate logistic regression analyses were carried out to identify risk factors associated with single-agent chemoresistance in low-risk GTN patients. Then, simplified models were built and compared with the original FIGO 2000 scoring system.@*RESULTS@#Among the eight FIGO risk factors, the univariate and multivariate analyses identified that pretreatment serum human chorionic gonadotropin (hCG) level and interval from antecedent pregnancy were consistently independent predictors for both first-line and subsequent single-agent chemoresistance. The simplified model with two independent factors showed a better performance in predicting single-agent chemoresistance than the model with the other four non-independent factors. However, the addition of other co-factors did improve the efficiency. Overall, simplified models can achieve favorable performance, but the original FIGO 2000 prognostic system still features the highest discrimination.@*CONCLUSIONS@#Pretreatment serum hCG level and interval from antecedent pregnancy were independent predictors for both first-line and subsequent single-agent chemoresistance, and they had greater weight than other non-independent factors in predicting single-agent chemoresistance. The simplified model composed of certain selected factors is a promising alternative to the original FIGO 2000 prognostic system, and it shows comparable performance.