Antônio Braga

Neoadjuvant chemotherapy with carboplatin and paclitaxel in pregnant women with advanced stage cervical cancer: Maternal and perinatal outcomes

Cervical cancer is the third most common cancer in Brazil. Although rare, its diagnosis during pregnancy represents a great challenge for the medical team and the patient. The objective of this study was to evaluate the maternal and perinatal outcomes of pregnant women who underwent neoadjuvant chemotherapy with carboplatin and paclitaxel for advanced stage cervical cancer. This was a descriptive, retrospective study that included pregnant women with advanced stage cervical cancer (IB3 a IIIC1) who were treated at our center over 12 years. These patients received neoadjuvant chemotherapy with carboplatin plus paclitaxel during pregnancy to prevent disease progression. Tumor shrinkage of at least 50 % was observed in four patients, while the disease remained stable in three others. There was one case of fetal death without apparent cause at 29 weeks, but all other mothers were discharged from the hospital at the same time as their healthy newborns. Chemotherapy with carboplatin and paclitaxel administered to pregnant women with advanced stage cervical cancer (IB3 - IIIC1) may have prevented disease progression without worsening neonatal outcomes.

Serum hCG levels in the prediction of molar pregnancy below 11 weeks of gestational age

The aim of this study was to evaluate the serum hCG level in the differential diagnosis between non-molar miscarriage and complete hydatidiform mole in16,435 mUI/mL at 6-7 weeks, hCG>64,911 mUI/mL at 8-9 weeks, and hCG >126,278 mUI/mL at 10-11 weeks were most prevalent on complete hydatidiform mole diagnosis. On the contrary, hCG<30,000 mUI/mL at 10-11 weeks was most prevalent in non-molar miscarriage diagnosis.

Atypical placental site nodule detected via hysteroscopy – first case report from Brazil

Atypical placental site nodule (APSN) is a rare form of gestational trophoblastic disease (GTD) originating from the proliferation of intermediate trophoblasts, with uncertain clinical behavior. It is considered a potential precursor to rare forms of gestational trophoblastic neoplasia (GTN), such as placental site trophoblastic tumor (PSTT) and epithelioid trophoblastic tumor (ETT). This report describes the first Brazilian case of APSN diagnosed via hysteroscopy in a 43-year-old woman following miscarriage. Histopathological analysis revealed a circumscribed, hyalinized aggregate of intermediate trophoblasts with nuclear atypia, positive immunostaining for PLAP and p63, and a Ki-67 index &gt; 5%. The patient declined hysterectomy, opting for conservative management with close monitoring. After 12 months of follow-up, no progression was observed. This case emphasizes the diagnostic challenges of APSN, given its subtle presentation and overlap with benign placental site nodules or even PSTT/ETT. Hysteroscopy proved valuable for both diagnosis and fertility-preserving management. Although hysterectomy remains the definitive treatment in many cases, individualized approaches balancing oncologic safety and reproductive goals are increasingly considered. Long-term clinical vigilance is essential, as APSN may precede aggressive GTN forms. Multicenter studies and registries are urgently needed to establish evidence-based guidelines for the diagnosis, treatment, and follow-up of this rare lesion, improving patient outcomes in these uncommon forms of GTD. Key words: atypical placental site nodule – gestational trophoblastic disease – gestational trophoblastic neoplasia – placental site trophoblastic tumor – epithelioid trophoblastic tumor

Human epidermal growth factor receptor 2 and proliferation Ki-67 biomarkers using a tissue microarray to refine the histopathological subtyping of hydatidiform moles: Limitations and prognostic value

The morphology-based differential diagnosis of Hydatidiform Mole (HM) of the Complete (CHM) and Partial (PHM) types is challenging because of earlier diagnosis of HM owing to the universal application of ultrasound during antenatal care. HMs may present with amplified oncogenes or other gene mutations, resulting in recurrent or neoplastic disease. The cell proliferation markers Ki-67 and HER2 may contribute to the final HM subtype and prognosis. Much is known about the basic mechanisms of HM development; however, other molecular diagnostic and predictive markers need to be investigated. This was an ambispective anatomopathological study of 108 HMs cases. A tissue microarray was used for Ki-67 or HER2 immunostaining analysis. Associations between immunomarker scores and postmolar Gestational Trophoblastic Neoplasia (GTN) were analyzed via Fisher's exact and linear-by-linear association tests. A statistically significant trend toward increased Ki-67 immunostaining in CHM samples was observed. Seventeen HM patients developed GTN, of whom 6 (35 %) had a Ki-67 score of 3+ and 9 (53 %) had Ki-67 score of 2+. Two (12 %) HM patients had a HER2 score of 3+, and 4 (23 %) HM patients had a HER2 score of 2+, of whom 2 (12 %) patients exhibited oncogene amplification by FISH HER2. Ki-67 and HER2 markers may be useful for the diagnosis and prediction of HM development, providing alternative targeted therapies. This study needs to be interpreted with caution due to its small sample size, high sample exclusion rate, and the absence of significant associations between biomarkers and clinical outcomes.

Analysis of the epidemiologic, clinical, laboratory, ultrasonographic, and anatomopathological profile of women with hydatidiform mole at two referral centers in Northeastern Brazil

Objective: To determine the profile of women undergoing uterine evacuation for suspected hydatidiform mole (HM) according to their clinical, laboratory, ultrasound, and anatomopathological characteristics at two referral centers in Northeastern Brazil. Methods: Retrospective cohort study was performed in two referral centers between October 2016 and December 2022 with women undergoing uterine evacuation for suspected HM. Socio-demographic characteristics, clinics, biochemistry, ultrasound, anatomopathology, and outcome were evaluated. Results: A total of 507 women were admitted with clinical suspicion of gestational trophoblastic disease, of which 334 were confirmed, with 107 being in Center-1 and 227 being in Center-2. Mean distance between the referral center and the patient‘s home was 88 km. Mean age of the women was 27 ± 9 years, with a predominance of 19 to 39 years (72%), and approximately 60% of the cases were diagnosed ≤ 12 weeks of gestation. Vaginal bleeding was observed in 79% of women. Transvaginal ultrasound showed a typical appearance in 90% of the examinations. The macroscopic aspect was described as a vesicle in 70% of cases. Uterine evacuation was mainly performed by uterine curettage (43%). The majority of women had no complications (69%). The outcome considered to be remission was achieved in 37.1% of cases, but 38.9% abandoned follow-up, and 9% did not start follow-up after hospital discharge. Conclusion: The distance traveled by women to the referral centers was significant, but the majority of women had no complications. Remission was observed in 37.1% of women, but there was a high abandonment rate of 38.9%. Key words: hydatidiform mole – clinics – ultrasound – anatomopathology – outcomes

Pembrolizumab in gestational trophoblastic neoplasia: Systematic review and meta-analysis with sub-group analysis of potential prognostic factors

To assess the performance of pembrolizumab for the treatment of Gestational Trophoblastic Neoplasia (GTN). The Medical Subject Headings related to immunotherapy/pembrolizumab and GTN were used alone or in combination to retrieve relevant articles. The authors searched in EMBASE, MEDLINE/PubMed, Elsevier's Scopus, and Web of Science until November/2024. The authors included any randomized controlled trials, cohort studies, case series, and case reports focusing on pembrolizumab treatment in GTN. Meta-analysis of proportions was carried out employing a random-effects model. The meta-analysis employed the inverse variance method, with the arcsine link function for the analysis of proportional data. All analyses were performed using Stata 18. For all analyses, a p-value < 0.05 indicated statistical significance. This study was registered on PROSPERO (CRD42023493329). A total of 550 studies were identified after a literature search among which 15 original studies were included in the systematic review and in the meta-analysis. Pembrolizumab induced complete sustained remission in 71.59% (95% CI 53.27‒84.78%; I Pembrolizumab seems an effective treatment for patients with high-risk GTN with chemoresistant or relapsed disease, including cases of PSTT/ETT, notwithstanding patient age, time to initiate immunotherapy and whether or not it was associated with chemotherapy.

Chemotherapy is not needed when complete evacuation of gestational choriocarcinoma leads to hCG normalization

The standard treatment for gestational choriocarcinoma is chemotherapy. To describe the risk of recurrence with expectant management of gestational choriocarcinoma that has reached a normal human chorionic gonadotropin level after tumor removal without adjuvant chemotherapy. A retrospective multicenter international cohort study was conducted from 1981 to 2017 involving 11 gestational trophoblastic disease reference centers with patient's follow-up extended until 2023. Clinical and biological data of included patients were extracted from each center's database. The inclusion criteria were i) histological diagnosis of gestational choriocarcinoma in any kind of placental tissue retrieved, ii) spontaneous normalization of human chorionic gonadotropin level following choriocarcinoma retrieval, iii) patient did not receive any oncological treatment for the choriocarcinoma, iv) and at least 6 months of follow-up after the first human chorionic gonadotropin level normalization. Among 80 patients with retrieved gestational choriocarcinoma and whose human chorionic gonadotropin level normalized without any other oncological therapy, none had a recurrence of choriocarcinoma after a median follow-up of 50 months. The median interval between choriocarcinoma excision and human chorionic gonadotropin level normalization was 48 days. The International Federation of Gynecology and Obstetrics/World Health Organization risk score was ≤6 in 93.7% of the cases. This multicenter international study reports that selected patients with gestational choriocarcinoma managed in gestational trophoblastic disease reference centers did not experience any relapse when the initial tumor evacuation is followed by human chorionic gonadotropin level normalization without any additional treatment. Expectant management may be a safe approach for highly selected patients.