A 10-year retrospective single-center study of alpha-fetoprotein and beta-human chorionic gonadotropin in Romanian children with (para)gonadal tumors and cysts

Objectives Malignant tumor is a top-ranking cause of pediatric (>1-year) mortality in America and Europe. Among pediatric tumors, germ cell tumors (GCT) and gonadal tumors rank fourth (6%) by the Surveillance, Epidemiology, and End Results (SEER) program (seer.cancer.gov). Continuous research on tumor markers harnesses their full potential in tumor detection and management. We evaluated the effectiveness of beta-human chorionic gonadotropin (β-hCG) and Alpha-fetoprotein (AFP) in Romanian children with (para)gonadal tumors and cysts, determining their accuracy in detecting malignancy, tumor-type, stage, complications, prognosis, and treatment response. Methods A 10-year retrospective study of AFP and β-hCG in 134 children with cysts and (para)gonadal tumors aged one month to 17 years was performed. Results AFP/β-hCG was unelevated in patients with cysts and nonmalignant tumors. Forty-eight/86 patients (43 GCT and 5 non-GCT) with malignant tumors had elevated AFP/β-hCG, 3/48 patients had recurrences, and 25/48 had mixed-GCT (68% had elevated AFP + β-hCG). All 30 patients with Yolk sac tumors (YST) or their components had elevated AFP. Area under the curve, sensitivity and specificity for GCT were: AFP + β-hCG- 0.828, 67.2%, 100%; AFP- 0.813, 64.1%, 100%; and β-hCG- 0.664, 32.8%, 100%. Two patients whose AFP/β-hCG levels remained elevated died. Common mixed-GCT components were YST-80% and embryonal carcinoma-72%. Thirty of 34 metastasis cases were GCT, with 26/34 patients having elevated AFP/β-hCG. Conclusions AFP/β-hCG detects malignant GCT and can determine tumor-type. GCT patients with markedly elevated AFP + β-hCG had poor prognosis, especially if recurrence or metastasis was present. Recurrence is unrelated to elevated AFP/β-hCG. The tumor components and quantity present determine AFP/β-hCG values in mixed-GCT.

A Rare Case of Epithelioid Trophoblastic Tumor Presenting as Hematoma of a Caesarean Scar in the Lower Uterine Segment

Epitheliod trophoblastic tumor (ETT) account for only 1–2% of all the cases of gestational trophoblastic neoplasia (GTN), with a reported mortality rate of 10–24%. ETT is derived from chorionic type intermediate trophoblastic cells, which appears to be the reason for the only slightly elevated βhCG levels in these patients. We present a case of a 42-year-old patient who was admitted to the clinic eight months after Caesarean delivery, for irregular vaginal bleed with normal values of beta-human chorionic gonadotropin (βhCG). A 6 × 5 cm hematoma was evacuated from the isthmic uterine segment during the operation, and the histopathological exam of the tissue surrounding the hematoma revealed ETT. There were no metastatic lesions on the thoracal, abdominal, and pelvic CT. The second ultrasonographic exam revealed tumefaction of 5 cm at the site from the previous surgical procedure. Color Doppler imaging revealed no central nor peripheral blood flow. The patient underwent a total abdominal hysterectomy with bilateral adnexectomy without adjuvant chemotherapy. This appears to be one of the shortest intervals from the anteceded gestational event until the diagnosis of this tumor, along with the absence of the significant ultrasonographic feature of the ETT-peripheral Doppler signal pattern. We underline that, even with normal values of βhCG, irregular vaginal bleeding following the antecedent gestational event should always arouse suspicion of GTN.

Unmasking of Gitelman Syndrome during Pregnancy in an Adolescent with Thyrotoxic Crisis

Background. Gitelman syndrome (GS) is an inherited salt-losing renal tubulopathy characterized by hypokalemic metabolic alkalosis with hypomagnesemia and hypocalciuria. Patients can be asymptomatic until late adolescence or adulthood, and hence may be discovered incidentally during presentation with other illnesses. GS has been described in association with thyroid disorders and should be considered in patients with hyperthyroidism and persistent hypokalemia, especially in those with associated hypomagnesemia and hypocalciuria. Case summary. In this report, we describe an 18-year-old female who presented with hyperemesis gravidarum and thyrotoxicosis, and was incidentally found to have GS, confirmed by the sequence analysis of SLC12A3. Conclusions. Thyroid dysfunctions, such as hypothyroidism, thyrotoxicosis, and thyroid nodules, may develop during pregnancy. A structural homology between the beta-human chorionic gonadotropin and thyroid stimulating hormone molecules, as well as their receptors is probably the basis for the transient thyrotoxicosis crisis during pregnancy. Since hyperemesis in pregnancy can also lead to hypokalemia and alkalosis, a high index of suspicion for GS during pregnancy is required for timely diagnosis and management.

Dual extrauterine ectopic pregnancy: double management

A 30-year-old nulliparous woman was referred with suspected left ovarian ectopic pregnancy. She had undergone laparoscopic left salpingectomy for ruptured tubal ectopic pregnancy 3 weeks earlier, following treatment with medications for ovulation induction. Sonological examination revealed a left ovarian ectopic pregnancy corresponding to 8 0/7 weeks with cardiac activity. She underwent ultrasound-guided intrasac therapy with intrasac instillation of 3 mEq of potassium chloride followed by 50 mg of methotrexate. She was followed with weekly measurements of serum beta human Chorionic Gonadotropin (hCG) which returned to baseline after 65 days of the intrasac therapy. This case not only highlights the need for continued follow-up of the serum beta hCG after definitive management of an ectopic pregnancy in cases with multiple ovulations, but also the option of medical management in cases of advanced ovarian ectopic pregnancy. It also accentuates the necessity for adequate counselling to avoid conception in a multiple ovulation cycle.

Role of Maternal Uterine Artery Doppler Versus Serum β-hCG During the First Trimester in the Prediction of Preeclampsia and IUGR

Objective: Preeclampsia accounts for 15% of maternal deaths and may cause fetal morbidity and mortality. The aim of this research was to evaluate the efficacy of maternal uterine artery Doppler versus serum beta-human chorionic gonadotropin (β-hCG), during the first trimester, in predicting preeclampsia and intrauterine growth restriction (IUGR). Materials and Methods: In a convenient sample of 388 pregnant women, uterine artery resistive index (RI) and pulsatility index (PI) were assessed, and serum β-hCG level was measured at 11 to 13 weeks of gestation. The patients’ maternal blood pressure and fetal growth were monitored. Results: The patients with preeclampsia (n = 58) showed a significant uterine RI and PI increase with a significant β-hCG decrease compared with the normotensive patients (n = 330). The specificity of uterine PI and RI to predict preeclampsia and IUGR is higher than that of β-hCG. However, the sensitivity of combined diagnostic tools is higher than the singular use of these diagnostic tests. Conclusion: Uterine artery Doppler may be better than serum β-hCG in predicting preeclampsia and IUGR. However, combined diagnostic techniques may be better to screen at-risk patients.

Cesarean scar pregnancy treatment: a case series

Background Cesarean scar pregnancy is a complicated and potentially life-threatening type of ectopic pregnancy. This study reports two women with cesarean scar pregnancy who were successfully treated with systemic methotrexate administration, and two other women who needed local re-administration of methotrexate after systemic injection. Case presentation Four Iranian pregnant women aged 29–34 years who were between 5 to 7 gestational weeks with cesarean scar pregnancy diagnosis are described. After a single dose of systemic methotrexate injection, the level of serum beta-human chorionic gonadotropin decreased in two of the women, while fetal activity was observed in the other two women. In the latter patients, methotrexate was injected under transvaginal ultrasound guidance into the gestational sac. As a result, the serum beta-human chorionic gonadotropin level first increased and then decreased in these patients. During the follow-up period, all the patients were stable and no complications were observed. Serum beta-human chorionic gonadotropin levels reached the non-pregnancy range from 4 to 9 weeks after treatment. Conclusion When diagnosed at early gestation, cesarean scar pregnancy can be treated successfully with methotrexate administration alone. The clinicians should be aware that the beta-human chorionic gonadotropin level may initially increase after methotrexate injection in some patients. However, the final outcome will be promising if the patients remain stable.

Primary Ovarian Choriocarcinoma: Rare Entity

Background. Primary pure ovarian choriocarcinoma is a rare aggressive tumor which can be nongestational arising from germ cells or gestational origin. Preoperative diagnosis of extrauterine choriocarcinoma is challenging due to nonspecific clinical presentation. Case Presentation. This article reports primary ovarian choriocarcinoma, likely gestational in a 25-year-old para 2 woman presenting with lower abdominal pain and swelling of two-week duration. Diagnosis was suspected by serum beta-human chorionic gonadotropin and confirmed histologically after surgery. Postoperatively, she was managed with multiple courses of chemotherapy using a bleomycin, etoposide, and cisplatin regimen, and the treatment was effective. Conclusion. In patients with adnexal mass presenting with nonspecific symptoms especially with high Doppler blood flow of the mass on ultrasound evaluation, serum beta-human chorionic gonadotropin determination is recommended before laparotomy. In setups where the genomic test is not available, histological and clinical effort to differentiate gestational versus nongestational choriocarcinoma is useful for specific management decision.

The Relationship Between First-Trimester Aneuploidy Markers and Birth Weight

OBJECTIVE: We aimed to determine the relationship between the first-trimester aneuploidy screeningma and the predicted weight at birth: Small for gestational age and large for gestational age. STUDY DESIGN: 594 low-risk pregnant women with a singleton pregnancy, who underwent first-trimester aneuploidy screening by measuring nuchal translucency, maternal serum free beta-human chorionic gonadotropin, and pregnancy-associated plasma protein-A were included in the study. Those weighing above the 3rd percentile and below the 10th percentile were defined as small for gestational age, and those over the 90th percentile were defined as large for gestational age. RESULTS: A total of 594 pregnant women were enrolled. The mean maternal age of the studied group was 28.8±5.5 years. Low maternal serum pregnancy-associated plasma protein-A levels and decreased nuchal translucency measurements were associated with the small for gestational age newborn (p<0.001 and p=0.001, respectively). There is a significant correlation with large for gestational age for newborns only with an increase in maternal serum pregnancy-associated plasma protein-A levels (p=0.001). beta-human chorionic gonadotropin levels were not associated with the birth weight (p=0.735). CONCLUSION: Maternal serum pregnancy-associated plasma protein-A levels, one of the markers in first-trimester aneuploidy screening, can be used in the prediction of small for gestational age and large for gestational age However, due to its low correlation, it is not a suitable screening test for clinical practice.

Placental Passage of Humulone and Protopine in an Ex Vivo Human Perfusion System

The placental passage of humulone and protopine was investigated with a human ex vivo placental perfusion model. The model was first validated with diazepam and citalopram, 2 compounds known to cross the placental barrier, and antipyrine as a positive control. All compounds were quantified by partially validated U(H)PLC-MS/MS bioanalytical methods. Only a small portion of humulone initially present in the maternal circuit reached the fetal circuit. The humulone concentration in the maternal circuit rapidly decreased, likely due to metabolization in the placenta. Protopine was transferred from the maternal to the fetal circuit, with a steady-state reached after 90 min. None of the study compounds affected placental viability or functionality, as glucose consumption, lactate production, beta-human chorionic gonadotropin, and leptin release remained constant. Histopathological evaluation of all placental specimens showed unremarkable, age-appropriate parenchymal maturation with no pathologic findings.