Trophoblastic Disease Research Articles

The role of single-dose prophylactic methotrexate in the prevention of post-molar gestational trophoblastic neoplasia in patients with high-risk molar pregnancy.

Prophylactic chemotherapy (PC) has been suggested to be effective in prevention of post molar gestational trophoblastic neoplasia (PGTN) in patients with high-risk molar pregnancies. The goal of this study is to assess the efficacy of single dose methotrexate as PC in terms of spontaneous remission, time to remission, and progression to PGTN. Patients with molar pregnancy were recruited to the study and underwent cervical dilation and suction curettage. Patients who had pathologically proven complete hydatidiform mole were evaluated with abdominal ultrasonography to confirm complete evacuation and absence of remnants. These patients were allocated to two groups: group one received Methotrexate 50mg/m2 via intramuscular injection, while group two did not. PGTN was defined according to the 2018 FIGO criteria. For patients with confirmed PGTN, the following variables were recorded: occurrence of metastasis, resistance to first-line chemotherapy and time to βHCG level normalization. Eighty patients were enrolled to the study, of which 22 cases (27.5%) received PC. It was found that PC with MTX did not significantly influence spontaneous remission (18 (81.8%) Vs 37 (63.7%), p value: 0.12) or time to remission (57 ± 22.5 Vs 61.24 ± 21.78 days, p value: 0.46) in high-risk molar pregnancies. Moreover, among patients in PC group and control group, 4 cases (18.2%) and 21 patients (36.3%) progressed to PGNT, respectively (p value: 0.12). Although patients in PC group tended to be diagnosed in lower stages compared to patients in control group, this difference was insignificance (p value: 0.95). Among patients who developed to PGTN, PC did not reduce the frequency of metastatic disease, resistance to first-line chemotherapy, or the time interval to serum βHCG level normalization (all p values > 0.05). This study suggests that a single-dose MTX as PC may not be an effective therapeutic option for preventing PGTN in patients with high-risk molar pregnancy.

Successful pregnancy outcome following selective uterine artery embolization in a case of perforating gestational trophoblastic neoplasia

Gestational trophoblastic neoplasia (GTN) includes a range of premalignant and malignant disorders of trophoblastic tissue. Invasive mole can present as a surgical emergency with rapidly progressive and highly vascular trophoblasts causing uterine perforation. Often hysterectomy is resorted to as a life-saving measure but in women desirous of future fertility, other options should be considered. We present the case of a nulliparous woman who presented with hemoperitoneum following perforating GTN. She was pale with stable vitals. Serum beta hCG at presentation was 98,156IU/L. Ultrasound pelvis revealed a highly vascular heterogenous hypoechoic mass of 5.8cm×5.5cm×6.5cm in the region of fundus and anterior myometrium showing significant internal and peripheral vascularity and displacing endometrium posteriorly. Ultrasound guided tap revealed hemoperitoneum. We decided for uterine artery embolization following clinical stabilization of the patient followed by chemotherapy. Figure 1 shows CT angiography done prior to uterine artery embolization. She conceived spontaneously two years later and was followed up closely in antenatal period. She was induced at 38 completed weeks due to oligohydramnios and decreased fetal movements and vaginally delivered a healthy baby with no postnatal complications. Fertility sparing procedures should be considered as a first possible option in selective cases. Multidisciplinary approach in high-risk cases is a key to optimal outcome.

Severe uterine haemorrhagic complications from gestational trophoblastic neoplasia

Severe uterine haemorrhagic complications from gestational trophoblastic neoplasia

Multiplying Meanings of Pregnancy Through Personal Accounts of Gestational Trophoblastic Disease

In cultures where reproduction is highly medicalised, pregnancy is often understood in terms of foetal development and an anticipated baby. This is connected to a wider privileging of the ‘foetal subject’ in these settings, which has had implications for reproductive autonomy. In this article, I disrupt dominant understandings of pregnancy by engaging with qualitative accounts of gestational trophoblastic disease. This rare condition can entail experiences of pregnancy without foetal development, allowing for scholarly attention to the wider biological, affective and relational constituents of this corporeal event. In this article, I pay particular attention to the ‘pregnancy hormone’ human chorionic gonadotropin (hCG), which in the context of gestational trophoblastic disease becomes a biomarker for disease. My research extends feminist science studies perspectives destabilising understandings of maternal and foetal bodies as bounded and distinct entities. The article de-centres foetal development as the most significant consequence of conception and enriches feminist discussions of reproductive politics.

Epithelioid trophoblastic tumor in male patients with germ cell tumor: A clinicopathologic analysis of five cases

Epithelioid trophoblastic tumor (ETT) is an extremely rare chorionic-type neoplasm in the testis, with only seven cases reported in the literature. Here, we report five cases of testicular ETT from a single institution, constituting the largest series of this rare tumor to date. The patients had a mean age of 44 years (range, 20–68 years). Four patients had a previous history of testicular germ cell tumor (GCT) treated with chemotherapy, and they developed ETT in metastatic sites in a mean of 11 years (range, 3–15 years) after the initial diagnosis of testicular GCT. Only one patient had ETT in the testis. Three patients had a normal serum beta–human chorionic gonadotropin (β-hCG) level, and two patients had a level that was slightly elevated, but far below that typically seen in patients with choriocarcinoma. ETT was characterized by a proliferation of intermediate trophoblastic cells with abundant eosinophilic cytoplasm, and the tumors frequently had coagulative necrosis with eosinophilic debris, mimicking keratinizing squamous cell carcinoma. The trophoblastic phenotype of ETT was supported by its immunoreactivity for trophoblastic markers, including GATA-3 (3 of 3 cases tested), α-inhibin (3/4), p63 (3/5), and β-hCG (3/4). ETT was also positive for cytokeratin (4/4) and GCT marker SALL4 (3/3). Despite surgery and chemotherapy, two patients died of disease 17 months after ETT diagnosis, and three patients were alive with metastatic disease at a mean of 20 months (range, 15–28 months). Our results demonstrate that ETT may be an aggressive disease associated with distinct pathologic features and poor clinical outcome.

Gestational Trophoblastic Tumours: Experience of the Oncology Department of the Moulay Ismail Military Hospital in Meknes (10 Cases)

Gestational trophoblastic tumors (GTTs) are the malignant forms of gestational trophoblastic diseases. They always follow a pregnancy, most often molar. The diagnosis of GTT is based on an abnormal course of HCG (chorionic gonadotropin hormone) and/or signs of ultrasound invasion and/or histological confirmation. We report a retrospective series of 10 cases of GTT collected at the Medical Oncology Department of the Moulay Ismail Military Hospital in Meknes over an 8-year period from January 2012 to January 2020. The analysis of our series led to the conclusion that: The average age of onsetis 42 years. 90% of our patients were pauciparic. The causal pregnancy was in 90% of the cases a molar pregnancy. The extension assessment was mainly based on the TAP CT identifying the lung as the main metastatic site in 40% of cases. 5 patients (50% of cases) underwent hysterectomy with post operative chemotherapy. 60% of our patients were classified as low risk according to the FIGO score and received methotrexate mono-chemotherapy. 4 patients were classified as high-risk and were treated with poly chemotherapy, the main protocol of which was EMA-CO. All our patients benefited from clinical and biological monitoring, before each chemotherapy session; then weekly and monthly after negativation, up to 12 months in case of good prognosis GTT, and up to 18 months in case of bad prognosis GTT. One case of MTX relapse (the case of IPTT) was reported and for which a 2nd line CMT with a favourable evolution was indicated. This study allowed us to analyze the cure rate, which was 100% for patients who were treated and had completed their monitoring.

Association of gestational trophoblastic disease with subsequent development of non-trophoblastic cancer.

To evaluate the association between gestational trophoblastic disease and the subsequent risk of developing non-trophoblastic cancer. We conducted a retrospective cohort study of 3084 women with gestational trophoblastic disease and 1 415 812 women with obstetric deliveries in Quebec, Canada, between 1989 and 2021. The main exposure was gestational trophoblastic disease, including hydatidiform moles, invasive moles, and gestational choriocarcinoma. The outcome was development of non-trophoblastic cancer during 33 years of follow-up. We measured the association of gestational trophoblastic disease with non-trophoblastic cancer using adjusted hazard ratios (HR) and 95% confidence intervals (CI), and tested whether associations were stronger for certain types of cancer or cancers with later onset. The incidence of non-trophoblastic cancer was greater for women with invasive moles (47.1/10 000 person-years) and gestational choriocarcinoma (59.3/10 000 person-years) than hydatidiform moles (18.4/10 000 person-years) and no gestational trophoblastic disease (22.4/10 000 person-years). Gestational choriocarcinoma (HR 2.33, 95% CI: 1.35-4.01; P = 0.002) and invasive moles (HR 1.97, 95% CI: 1.06-3.65; P = 0.033) were associated with an elevated risk of non-trophoblastic cancer compared with no gestational trophoblastic disease, while hydatidiform moles were not. Gestational choriocarcinoma and invasive moles were mainly associated with gynecologic cancer. However, risk of cancer was limited to the short-term period after pregnancy and became similar to no gestational trophoblastic disease by the end of follow-up. While invasive moles and gestational choriocarcinoma appear to be associated with the subsequent development of non-trophoblastic cancer, the absolute risk is small and limited to the short-term.

Pathologic findings of the placenta and clinical implications - recommendations for placental examination.

The placenta is a unique and complex organ that combines the circulatory systems of two or more individuals within a single dynamic organ with a set, short lifespan. A diverse spectrum of disorders, including infections as well as metabolic, genetic, circulatory, and maturation defects, may affect its function. Pathology investigation of the placenta is key for identifying several pathogenic processes in both the mother and the foetus. Aberrant placentation, maternal and foetal vascular compromise, infection, inflammatory immunologic conditions, and disorders of maturation are elements of newly proposed classification schemes. The clinical impact of placental examination consists of diagnosing maternal and foetal disease, identifying the potential for recurrence, correlating clinical pathological findings with distinct morphologic features, and identifying the aetiology responsible for growth restriction or foetal death. Gestational trophoblastic disease occurs more frequently in the first trimester; however, in very rare cases, it can affect the term or third-trimester placenta. The application of reproducible nomenclature is expected to facilitate progress in the diagnosis and treatment of obstetric and foetal disorders with placental manifestation. Therefore, this review aims to facilitate communication between obstetricians, neonatologists, and pathologists involved in this diagnostic process.

Multifocal Hemorrhagic Choriocarcinoma With Diffuse Pancreatic FDG Uptake on 18F-FDG PET/CT.

Choriocarcinoma is a rare and highly malignant trophoblastic tumor. We present a case involving a 30-year-old woman with abdominal pain, hemoptysis, and elevated serum amylase levels. Initial clinical suspicion included acute pancreatitis. Noncontrast and contrast-enhanced CT revealed hemorrhagic and hypervascular lesions in the lungs, pancreas, liver, and kidneys. 18F-FDG PET/CT showed diffuse pancreatic enlargement with increased FDG uptake (SUVmax, 5.3), consistent with malignancy. Histopathology confirmed choriocarcinoma with elevated HCG levels. Following chemotherapy, HCG levels declined, indicating a positive therapeutic response. 18F-FDG PET/CT effectively detected choriocarcinoma and assessed its systemic involvement.

Metastatic Intracranial Choriocarcinoma in the Absence of a Primary Lesion: A Case Report

AbstractIntracranial choriocarcinoma is a rare and aggressive neoplasm characterized by the proliferation of trophoblastic tissue. Although choriocarcinoma most commonly arises in the uterus as a component of gestational trophoblastic neoplasia, instances of intracranial choriocarcinoma are exceptionally uncommon. We report a case of intracranial choriocarcinoma without any evidence of a tumor elsewhere. A 25-year-old woman presented with a history of 1 month of evolution with right frontal hemicranial headache, followed by visual disturbances, otalgia, and diplopia. On neurological examination, she was conscious, cooperative, and well-oriented; a grade 1 bilateral papilledema, left homonymous hemianopsia, and sixth cranial nerve paresis, with diplopia, were detected. Neuroimaging showed a right parieto-occipital lesion with features mimicking an atypical meningioma. After surgical resection, a diagnosis of choriocarcinoma was issued. Primary intracranial choriocarcinomas are typically located in the sellar and pineal regions. The occurrence of this tumor within the occipital lobe suggested metastasis; however, a primary tumor in the thoracic or abdominal organs was not observed and a delayed metastasis was considered. This case highlights the diagnostic challenges associated with intracranial choriocarcinoma.

7617 Two Cases of Severe Beta-hCG-Mediated Hyperthyroidism with Gestational Trophoblastic Disease

Abstract Disclosure: A. Morvant: None. M. Mashayekhi: None. Introduction: Hyperthyroidism is most commonly caused by Graves’ disease and toxic nodules and affects 2.5% of the world’s population. Hyperthyroidism due to elevations in beta-hCG (b-hCG), which has thyroid-stimulating activity due to homology with TSH, is a rare process that requires high clinical suspicion. We present two cases of hyperthyroidism caused by severely elevated b-hCG due to gestational trophoblastic disease (GTD), with rapid resolution of hyperthyroidism after treatment of the underlying conditions. Clinical Cases Case 1: A 35-year-old at 28-weeks gestation presented with dyspnea, palpitations, and 6-pound weight loss over the prior month. Labs revealed b-hCG 5.2 million (0-5 mIU/mL), TSH <0.015 (0.35-3.6 mcU/mL), and free T4 2.42 (0.7-1.37 ng/dL). Imaging revealed extensive pulmonary lesions concerning for metastatic disease and a 2.4 cm ovarian mass. Due to worsening respiratory distress and the need to start chemotherapy urgently, she underwent Cesarean section to deliver the viable infant and take out the ovarian mass. Pathology confirmed choriocarcinoma. Methimazole was started post-operatively, and she started chemotherapy. Labs after cycle one of chemotherapy showed b-hCG 1.3 million, TSH <0.015, and free T4 1.46. The methimazole dose was decreased and ultimately stopped as free T4 levels decreased with subsequent chemotherapy cycles. After three cycles, labs showed b-hCG 4,652, TSH 1.55, and free T4 0.68. She was discharged without thyroid-targeting therapy. Case 2: A 33-year-old woman at 12-weeks gestation presented with nausea, vomiting, and 10-pound weight loss over 1 month. Labs showed TSH <0.015, free T4 2.39, and total T3 351 (58-160 ng/dL), which were thought to be due to hyperemesis gravidarum. Two months later she presented with vaginal bleeding and imaging showed an enlarged placenta with a moth-eaten appearance and theca lutein cysts concerning for partial molar pregnancy. Beta-hCG level was 3.3 million, TSH <0.015, free T4 1.76, and total T3 289. She underwent dilation and evacuation and pathology confirmed partial hydatidiform mole. Beta-hCG level decreased to 1.8 million and free T4 normalized after surgery, with b-hCG 3,300, normal TSH, and normal total T3 one month later. Conclusion: These cases highlight the importance of considering possible GTD when evaluating a patient with hyperthyroidism, particularly in women of childbearing age and cases of early pregnancy when the degree of hyperthyroidism seems out of proportion to that expected. Clinicians should consider checking a b-hCG level in consultation with an obstetrician when indicated. Treatment is aimed at the GTD and can yield rapid resolution of hyperthyroidism.

FcγR3A polymorphism influences natural killer cell activation and response to anti-PD-L1 (avelumab) in gestational trophoblastic neoplasia

BackgroundLow-risk gestational trophoblastic neoplasia (GTN) are currently receiving monochemotherapy as first-line therapy. In the case of a resistance, a second-line mono- or polychemotherapy is proposed. As an alternative to these toxic and historic chemotherapy agents, the efficacy of the anti-PD-L1 monoclonal antibody (avelumab) was assessed in the TROPHIMMUN phase II trial Cohort A. Avelumab yielded a 53% cure rate with an acceptable tolerance profile, including normal further pregnancy and delivery. Beyond the blockade of PD-1/PD-L1 interactions, avelumab effect could rely on the induction of antibody-dependent cell-mediated cytotoxicity (ADCC) mediated by FcγR3A-expressing natural killer (NK) cells. ObjectiveThis translational study aimed at testing whether ADCC is involved in avelumab efficacy on GTN and if FcγR3A affinity polymorphism could help predicting the response to avelumab in GTN. Study DesignThe expression of PD-L1 by the tumor and the phenotype of NK cells infiltrating GTN were verified by performing transcriptomic and proteomic analyses. Then, JEG-3 choriocarcinoma cells were cocultured with human NK cells in presence and absence of avelumab. The impact of FcγR3A functional polymorphism was assessed on the activation status of NK cells and the viability of JEG-3 choriocarcinoma cells. Finally, the data from TROPHIMMUN trial were reanalyzed to determine the impact of the FcγR3A polymorphism of patients on their response to avelumab. ResultsWe confirmed that FcγR3A+ NK cells infiltrated PD-L1-expressing GTN. In vitro, avelumab-coated JEG-3 choriocarcinoma cells induced NK cell activation, which promoted the destruction of JEG-3 cells. NK cell activation was abolished when the Fc portion of avelumab was removed, demonstrating the importance of Fcγ receptor in this process. Using this model of ADCC, we demonstrated that high-affinity FcγR3A polymorphism on NK cells was associated with better in vitro response to avelumab. In line with this result, patients from the TROPHIMMUN trial homozygous for the high affinity FcγR3A polymorphism had better clinical response to avelumab. ConclusionsOur work demonstrates that ADCC contributes to the therapeutic effect of avelumab in GTN and that the individual patient response is impacted by the FcγR3A polymorphism. The FcγR3A polymorphism could be used as a biomarker to identify patients diagnosed with monochemoresistant GTN who are most likely to respond to avelumab.

B-312 Overcoming Challenges in Reporting High ß-hCG Results In Cancer Patients: A Tertiary Cancer Institute Experience

Abstract Background Serum ß-hCG is levels are a useful marker for diagnosis of Gestational Trophoblastic Disease as well as germ cell tumours of the ovary and testicle. However, values ranging from 50,000 - 1,00,000 mIU/ml are commonly seen in malignancies which are beyond the linearity of the most methods used in routine practice. This poses a great challenge to laboratory professionals while reporting for this test as serial monitoring of ß-hCG values is essential for ascertaining the effectiveness of treatment and progression of disease in oncology patients. The aim of this study was to develop a protocol for reporting beyond linearity values of serum ß-hCG in our laboratory with comparison of the same on two analysers with different linearity. Methods One hundred and fifty serum samples for ß-hCG received from patients with trophoblastic as well as germ cell tumours over a period of three months from October 2023 to December 2023 were processed by Chemiluminescence Immunoassay (CLIA) method on Atellica IM (Siemens Healthineers) and Alinity-i (Abbott Healthcare) immunoassay analysers simultaneously. The linearity for Atellica IM is 0 -1000mIU/ml and same for Alinity-i is 0- 15,000 mIU/ml as reported by the manufacturer. The protocol followed for samples processed on Atellica IM was as follows with 50 samples in each group. For values of ß-hCG less than 500 mIU/ml, we repeat tested samples with 1:10 dilution in case any instrument flags were observed in the report. For values between 500-1000 mIU/ml, samples were repeat tested with 1:50 dilution. For values reported as >1000 mIU/ml, samples were repeat tested with 1:5000 dilutions. For Alinity-i, samples with values higher than 15,000 mIU/ml were processed with a dilution of 1:10. For all results with instrument flags, the dilution protocol was followed. Diluent provided by the manufacturer was used for all sample dilution processes. The values obtained on both analysers were compared statistically for correlation using linear regression analysis and coefficient of correlation (R) was calculated. Results The serum ß-hCG values observed ranged from 102 mIU/ml to 187,000 mIU/ml. Linear regression analysis for all groups showed good correlation. For serum ß-hCG values < 500 mIU/ml; between 500-1000 mIU/ml and >1000 mIU/ml coefficient of correlation was observed as R=0.9987, 0.9936 and 0.9713 respectively. Conclusions Good correlation was observed between values of serum ß-hCG obtained by dilution protocol on Atellica IM and Alinity-i analysers. The protocol developed by our laboratory to report beyond linearity sample results on Atellica IM can be a very useful tool in oncology patients where high values of beta HCG are expected and serial monitoring of values is essential.

Analysis of Fertility Prognosis and Risk Factors in Patients Post-Gestational Trophoblastic Disease.

To retrospectively analyze the fertility outcomes and prognosis of gestational trophoblastic disease (GTD) patients, providing a basis for targeted fertility guidance and counseling. 82 GTD patients of childbearing age who received treatment at the Obstetrics and Gynecology Department of Lanzhou University First Hospital from January 2016 to January 2023 were stratified into re-pregnancy (n = 20) and non-re-pregnancy (n = 33) cohorts based on their pregnancy outcomes. The impacts of various factors on pregnancy outcomes were subsequently evaluated, encompassing the rates of subsequent pregnancies, live births, miscarriages, ectopic pregnancies, and ongoing pregnancies. Finally, logistics regression model was employed to analyze the risk factors affecting re-pregnancy in GTD patients. The study delineated those patients with different GTD pathologies had varying re-pregnancy rates (mole, erosive mole and choriocarcinoma accounted for 66.04%, 30.19% and 3.77%, respectively). Treatment predominantly involved uterine curettage, with fewer cases receiving chemotherapy alone or in conjunction with curettage accounted for 67.92%, 5.66%, and 26.42%, respectively. The average chemotherapy frequency was 4.59 ± 2.43 sessions, and a majority sought reproductive counseling. Re-pregnancy occurred in 37.74% of patients. The live birth rate was 65.00%, with miscarriage and ectopic pregnancy rates at 25.00% and 5.00% respectively. Logistic regression analysis pinpointed the absence of pre-pregnancy counseling as a significant independent risk factor for re-pregnancy in GTD patients (p < 0.05). While chemotherapy may influence ovarian function, with the majority of patients desiring children post-recovery, pregnancy rates remain high. Fertility counseling significantly enhances re-pregnancy success rates in GTD survivors, emphasizing its recommendation for those aiming to conceive post-recovery.

Trophoblastic disease and choriocarcinoma

Gestational trophoblastic disease (GTD) is a group of diseases associated with pregnancies that demonstrate abnormal development of trophoblastic cells. GTD includes hydatidiform moles (HM) that may continue to further develop into gestational trophoblastic neoplasms (GTN), such as choriocarcinoma (CC). Gestational CC is a malignant mass development that may arise from HM, from other (normal) pregnancies or from other gestational events (such as ectopic pregnancies). The aim of this review is to outline current understating of the genetics and epigenetics of GTD and gestational CC and the link between the two diseases.

Differential diagnosis of non-molar gestational trophoblastic neoplasia with ectopic pregnancy by clinical-pathological features.

This study was presented to investigate the clinical-pathological characteristics of gestational trophoblastic neoplasia (GTN) following non-molar pregnancy and differentiated with ectopic pregnancy (EP). The clinical data of 83 patients who were admitted for suspected GTN after non-molar pregnancy at the Women's Hospital School of Medicine Zhejiang University from January 2015 to September 2022 were selected for analysis. In total, 41 cases were confirmed non-molar GTN, including 31 choriocarcinoma, 9 PSTT (placental site trophoblastic tumor), and 1 ETT (epithelioid trophoblastic tumor), while 42 cases were confirmed EP. Compared with ectopic pregnancy, non-molar GTN patients had lower levels of serum progesterone compared with EP (3.81nmol/L vs 17.70nmol/L, P = 0.001). Based on the ultrasound, the thickness of the endometrium was thinner in patients with non-molar GTN compared with EP (0.565cm vs 0.70cm, P = 0.018). By histopathologic examination, the endothelium of non-molar GTN showed less decidual-like changes compared with EP (64.3% vs 14.6%, P = 0.001). A combination of serum progesterone levels, endometrium thickness, and histopathologic features of the endometrium can help to differentiate non-molar GTN and EP. Surgeries including hysteroscopy with curettage and/or laparoscopy are needed.

Methotrexate: Use in the Post Dobbs v. Jackson Era.

Methotrexate is one of the most frequently used medications for the treatment of rheumatic diseases. Although initially developed for use as chemotherapy for both solid and hematologic malignancies, it was used as early as the 1960s with success for rheumatoid arthritis (RA) and psoriatic arthritis, ultimately being approved by the US Food and Drug Administration for the treatment of RA in 1988. Beyond RA and psoriatic arthritis, methotrexate is used in the treatment of systemic lupus erythematosus, idiopathic inflammatory myopathies, and other inflammatory conditions. Methotrexate is cytotoxic to the trophoblast and has been used to treat both ectopic pregnancy and gestational trophoblastic neoplasia, leading to studies in the early 1990s that showed it was effective and safe for early abortion in combination with prostaglandin E1 analog misoprostol. Methotrexate is also a teratogen, causing serious birth defects in 6%-10% of patients taking it while pregnant. Additionally, women are more likely to be affected by both RA at SLE, as compared with males, thus worsening the burden of these adverse effects. Both methotrexate's history of use as an abortifacient and its teratogenic properties make its use more complicated in the current era of abortion policy in the United States following the Dobbs v. Jackson Women's Health Organization ruling. Recently published data suggest that this ruling has affected both provider perspectives and patient experiences as it relates to methotrexate use. In the post-Dobbs era, the role of the rheumatologist as it relates to patients' sexual and reproductive health is likely to expand.

Predicting monotherapy resistance risk in patients with low-risk gestational trophoblastic neoplasia: integration of the systemic immune-inflammation index and the prognostic nutritional index.

Currently, there are no reliable indicators for the early identification of patients with low-risk gestational trophoblastic neoplasia (GTN) who develop resistance to monotherapy. This study aimed to evaluate the effectiveness of combining the Systemic Immune-Inflammation Index (SII) and Prognostic Nutritional Index (PNI) in detecting early resistance to monotherapy in patients with low-risk GTN. This retrospective study included 91 patients with low-risk GTN who received initial monotherapy at Fujian Maternal and Child Health Hospital between 2013 and 2021. The SII and PNI before chemotherapy were calculated from prechemotherapy peripheral blood samples, with cut-off values determined by receiver operating characteristic (ROC) curves. The SII-PNI score ranged from 0 to 2 points and was categorized as follows: a score of 2 points indicated a high SII (≥467.02) and a low PNI (≤51.35); a score of 1 point indicated either a high SII or a low PNI; and a score of 0 points indicated neither a high SII nor a low PNI. Ninety-one patients with low-risk GTN underwent monotherapy, 19 of whom developed resistance, whereas the remaining 72 did not. The SII was significantly greater in chemotherapy-resistant patients than in non-resistant patients (P=0.04), whereas the PNI was markedly lower in chemotherapy-resistant patients (P=0.002). Univariate analysis revealed that cut-off values of 467.02 for the SII (P=0.04) and 51.35 for the PNI (P=0.024) were associated with chemotherapy resistance in patients with low-risk GTN. As the SII-PNI score increased, the proportion of chemotherapy-resistant patients increased (P<0.001), and the time for human chorionic gonadotropin (hCG) normalization correspondingly increased (P<0.001). Multivariate logistic regression analysis indicated that a high SII-PNI score is an independent risk factor for chemotherapy resistance in patients with low-risk GTN (P=0.001). A high SII and low PNI are linked to chemotherapy resistance in patients with low-risk GTN. The pretreatment SII-PNI score is a key indicator for predicting the sensitivity of patients with low-risk GTN to single-agent chemotherapy, aiding in the early identification of individuals at high risk of resistance.

Machine learning-driven survival prediction in gestational trophoblastic neoplasms: a focus on PSTT and ETT prognosis.

The clinicopathological characteristics and prognosis of placental site trophoblastic tumor (PSTT) and epithelioid trophoblastic tumor (ETT) have not been well summarized. Consequently, we conducted the largest to date series of samples of both types and employed machine learning (ML) to assess treatment effectiveness and develop accurate prognostic models for patients with GTN. Gestational choriocarcinoma (GCC) was used as the control group to show the clinical features of PTSS and ETT. The Surveillance, Epidemiology, and End Results (SEER) database provided the data used for this study's analysis. To identify the prognostic variables, we conducted Cox regression analysis and constructed prognostic models using five ML algorithms to predict the 5-year survival. A validation method incorporating the area under the curve (AUC) of the receiver operating characteristic (ROC) curve was used to validate the accuracy and reliability of the ML models. We also investigated the role of multiple therapeutic options using the Kaplan-Meier survival analysis. The study population comprised 725 patients. Among them, 139 patients had ETT, 107 had PSTT, and 479 had GCC. There were no significant differences in survival between the different tumor groups. Multivariate Cox regression analysis revealed that metastasis was a significant prognostic factor for GCC, while older age and radiotherapy were significant prognostic factors for PTSS and ETT. ML models revealed that the Gradient Boosting classifier accurately predicted the outcomes, followed by the random forest classifier, K-Nearest Neighbors, Logistic Regression, and multilayer perceptron models. The most significant contributing factors were tumor size, year of diagnosis, age, and race. Our study provides a method for treatment and prognostic assessment of patients with GTN. The ML we developed can be used as a convenient individualized tool to facilitate clinical decision making.

A comprehensive diagnostic approach to differentiate intrauterine arteriovenous malformation in cases of enhanced myometrial vascularity.

The differentiation between conditions such as uterine arteriovenous malformation, pseudoaneurysm, gestational trophoblastic disease, and retained trophoblastic tissue can be challenging. Ultrasound imaging and Doppler interrogation are the primary diagnostic tools to assess cases of enhanced myometrial vascularity and differentiate intrauterine vascular anomalies. However, some cases remain of difficult differentiation. This study aims to analyze suspected cases and describe their diagnostic management and outcomes. We reviewed post-abortion cases that underwent pelvic transvaginal U/S imaging and Doppler examinations due to suspected uterine vascular anomalies. CT scans were performed in cases in which ultrasound did not reach a diagnosis. Simple follow-up, medical or surgical therapy, or embolization of uterine arteries were performed according to the final diagnosis. From 2015 to 2022, we retrieved from electronic ultrasound records 22 cases of suspected vascular malformations. In eight cases, first-line U/S at admission excluded the suspected anomaly.In Five ofthe remaining 14 patients, uterine vascular anomalies were excluded upon a second-level U/S based on angio-Doppler imaging and Doppler peak velocity interrogation. Nine cases underwent CT scan, and a digital angiography and embolization were performed in eight of these cases, of whom only two had a documented uterine arteriovenous malformation. Our triage proved that only two out of 22 suspected cases had a uterine arteriovenous malformation. This diagnosis is frequently misused in clinical practice. Our data confirm that enhanced myometrial vascularity should be used to encompass the spectrum of possible differential diagnosis. A precise step-by-step diagnostic method is of paramount importance to prevent unnecessary interventions.