Subunit Of Human Chorionic Gonadotropin Research Articles

Clinical Features and Treatment Outcomes in Patients with Extracranial Germ Cell Tumors: A Tertiary Centre Experience

Background: Germ cell tumors are histologically heterogeneous group of tumors with high cure rate if diagnosed early. The aim of study was to evaluate the extracranial germ cell tumors presenting to our institute with regards to gender, age, clinical presentation, pathology, management, acute toxicity and survival. Material and Methods: This retrospective study was conducted at Department of Radiation Oncology, All India Institute of Medical Sciences (AIIMS), Patna. Results: Total of 75 patients with germ cell tumor (GCT) were analysed. Distribution of males and females were 50.7% and 49.3% respectively. The median age of presentation of males and females was 31 years and 15 years respectively. At the time of presentation, 47.3% male and 16.2% of female patients had metastatic disease. The median alpha-fetoprotein (AFP), beta subunit of human chorionic gonadotropin (βHCG), and lactate dehydrogenase (LDH) were 112 ng/ml, 668 mIU/ml, and 550 U/L respectively. At median followup of 34 months, 32% of the patient developed recurrence. The median disease-free survival (DFS) and overall survival (OS) were 57 months and 71 months respectively. Multivariate analysis showed that the histological subtypes (p = 0.001) and risk groups (p = 0.029) were the independent prognostic factors for DFS, while metastatic status at presentation (p = 0.037), upfront surgical intervention (p =0.039), and histopathological subtypes (p = 0.009) were the independent prognostic factor for OS. Conclusion: GCT is primarily a disease of young and adolescents. Early diagnosis, well-orchestrated multidisciplinary management leads to favourable outcome and survival.

Evaluation of Maternal Serum sHLA-G Levels for Trisomy 18 Fetuses Screening at Second Trimester.

Human leukocyte antigen-G (HLA-G) has been widely acknowledged to play critical roles in fetal-maternal maintenance. However, the significance of using maternal serum sHLA-G to detect prenatal chromosomal abnormality has not been investigated. In China, prenatal screening using maternal α-fetoprotein (AFP), unconjugated estriol (uE3), and free β subunit human chorionic gonadotropin (β-hCG) in the second trimester has been widely applied. In this study, we evaluated the use of sHLA-G as a screening marker, compared with traditional second trimester prenatal screening. Serum samples from 1,019 singleton women in their second trimester were assessed. Among them, 139 infants were confirmed with trisomy 21 (T21) by karyotyping, 83 were confirmed with trisomy 18 (T18), and the remaining 797 infants had no abnormalities. The sHLA-G levels in maternal sera were significantly lower in pregnant women with T18 fetuses (median: 47.8 U/ml, range: 9.8–234.2 U/ml) and significantly higher in those with T21 fetuses (median: 125.7 U/ml, range: 28.7–831.7 U/ml), compared with the normal controls (median: 106.3 U/ml, range: 50.5–1136.4 U/ml) (p < 0.001). The risk values of the screening of T21 or T18 fetuses were assessed using mean and standard deviation log10 analyte multiples of median (MoM) which showed that the predictive values of sHLA-G were the same as free β-hCG, and superior to AFP and uE3 for T18 screening. Logistic regression analysis revealed that sHLA-G MoM was the highest risk factor associated with pregnant women carrying T18 fetuses [Exp(B): 171.26, 95% CI: 36.30–807.97, p < 0.001]. Receiver operating characteristic (ROC) analysis revealed that the area under ROC curve for sHLA-G MoM was 0.915 (95% CI, 0.871–0.959, p < 0.001), for AFP MoM was 0.796 (95% CI, 0.730–0.861, p < 0.001), for free β-hCG MoM was 0.881 (95% CI, 0.829–0.934, p < 0.001), and for uE3 MoM was 0.876 (95% CI, 0.828–0.923, p < 0.001) in the T18 group. sHLA-G MoM demonstrated the best sensitivity and negative predictive value. For the first time, our findings reveal that sHLA-G is a better second trimester screening marker for the detection of T18 fetuses and the combined application of sHLA-G with AFP, free β-hCG, and uE3 could improve clinical screening for T18 fetuses.

THYROTOXICOSIS IN PATIENTS WITH HYDATID MOLE

Mola Hydatidosa, juga sering disebut hamil anggur, merupakan kehamilan yang ditandai dengan perkembangan trofoblas yang tidak normal. Insiden mola hidatidosa per 1.000 kehamilan terjadi di Asia. Di Indonesia, pada tahun 2002 ditemukan kasus mola hidatidosa 1:123 kehamilan, dan pada tahun 2003 ditemukan kasus mola hidatidosa 1:245 kehamilan. Sedangkan hasil penelitian yang dilakukan di tempat yang sama pada tahun 2012–2013 diperoleh sebanyak 39 kasus mola hidatidosa yang didistribusi berdasarkan kelompok umur, paritas, pendidikan, dan kadar hemoglobin penderita. Hipertiroid Trofoblastik adalah kasus yang jarang tetapi dapat mengancam jiwa. Alfa subunit-human chorionic gonadotropin (HCG) menyerupai dengan alfa sub unit-thyroid stimulating hormon (TSH). Jika konsentrasi HCG meningkat pada waktu yang panjang, hal itu dapat meningkatkan kadar free T4 dan free T3. Pada pasien ini didapatkan pula terjadinya hipertensi mendadak, proteinuria 3+, ketonuria 3+, hematuria 3+, lekosituria 1+, bakteriuria yang kemungkinan dapat disebabkan oleh karena terjadinya suatu pre-eklampsia atau ISK pada pasien ini. Penyebab terjadinya pre-eklampsia pada kehamilan mola diperkirakan oleh karena berlebihannya kadar soluble fms-like tyrosine kinase 1 (sFlt1) di sirkulasi, protein anti-angiogenic endogen yang masuk ke sirkulasi ibu setelah diproduksi berlebihan di placenta.

PRIMARY MEDIASTINAL SEMINOMA FOUND ON EVALUATION FOR WEIGHT LOSS

SESSION TITLE: Medical Student/Resident Disorders of the Mediastinum Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Extragonadal germ cell tumors (GCTs) typically arise in midline locations such as mediastinum and retroperitoneum. They are formed either due to failure of primordial germ cells to migrate to the gonadal ridges [1] or reverse migration of the transformed germ cells in the testes [2]. Mediastinal seminomas are rare tumors constituting about 1/3rd of malignant mediastinal GCTs and 2-4 percent of mediastinal masses [3]. CASE PRESENTATION: A 55-year-old man with a history of active smoking (½ pack cigarettes per day), hepatitis C, bipolar disorder, prior alcohol/intravenous drug use (heroin and cocaine) presented with shortness of breath and 50-pound weight loss. Chest computed tomography (CT) revealed a 3.0 x 1.1 cm para-aortic lymph node. Positron emission tomography (PET/CT) scan showed hypermetabolic activity (maximum standardized uptake value of 10). Bronchoscopy with EBUS (endoscopic ultrasound) and mediastinoscopy were considered as methods to obtain tissue but discarded due to the location of the mass. He underwent a left Video-assisted thoracoscopic surgery (VATS) which showed seminoma. H&E (hematoxylin and eosin) slides revealed pale tumor cells with distinct nuclei and prominent central nucleoli in a background of lymphocytic infiltrate. The tumor cells stained positive for germ cell markers CD117, Oct 3/4 and Sall 4; but were negative for melanoma markers (Mart1a, S100), as well as CK20, CK7, Pancytokeratin, CD30, CD15, TTF1 and CDX2. DISCUSSION: Mediastinal seminomas occur mainly in men aged 20 to 40 years. They are typically slow growing and can be very bulky by the time they cause symptoms. Serum beta subunit of human chorionic gonadotropin (beta-hCG) is elevated in approximately one-third of patients. They do not produce alpha-fetoprotein (AFP). Ultrasound is advised in all cases to evaluate for any testicular primary. Seminomas are exquisitely sensitive to both cisplatin-based chemotherapy and radiotherapy (RT) but local control with surgery and RT only have modest success due to their typically later presentation. The commonly used chemotherapy regimens are 3 cycles of bleomycin/etoposide/cisplatin (BEP) or 4 cycles of etoposide/cisplatin (EP) (in patients who have previously received RT, who have underlying lung disease or age more than 50 years to avoid bleomycin lung toxicity). Long-term disease-free survival is achieved in roughly 90 percent of patients treated with chemotherapy. CONCLUSIONS: Primary mediastinal seminoma is a malignant extragonadal GCT most commonly found in the anterior mediastinum. Usually, young men in their 20-40s present with large 4-11cm anterior mediastinal masses which cause symptoms by compressing local structures. Or, as in our case, they are found incidentally. Surgery/RT can be considered but many patients present late so local control is not possible. However, these tumors respond well to chemotherapy with complete response rates of 90% Reference #1: Intracranial germ cell tumors: a comprehensive review of proposed embryologic derivation; Glenn OA, Barkovich AJ; Pediatr Neurosurg. 1996;24(5):242; PMID 8933567 Reference #2: Genetics and biology of adult human male germ cell tumors; Chaganti RS, Houldsworth J; Cancer Res. 2000;60(6):1475; PMID 10749107 Reference #3: Primary germ cell tumors of the mediastinum: II. Mediastinal seminomas--a clinicopathologic and immunohistochemical study of 120 cases; Moran CA, Suster S, Przygodzki RM, Koss MN; Cancer. 1997;80(4):691; PMID 9264352 DISCLOSURES: No relevant relationships by William Han, source=Web Response No relevant relationships by Sahib Singh, source=Web Response

SUN-523 Thyroid Storm: A Rare Presentation of HCG Producing Metastatic Choriocarcinoma

Background: The beta subunit of human Chorionic Gonadotropin (hCG) and TSH are very similar and hCG is known to weakly bind the TSH receptor. hCG induced hyperthyroidism has been previously reported as a rare paraneoplastic syndrome in non-seminomatous germ-cell tumors and usually presents with subclinical thyrotoxicosis. We present a noteworthy case of thyroid storm in a patient with hCG producing testicular Choriocarcinoma. Clinical case: A 19-year-old Hispanic man presented to an outside emergency department (ED) with one day of abdominal pain, nausea, recurrent emesis and subjective fever. He had presented to the same ED 9 days prior with similar symptoms which prompted contrasted CT Abdomen/Pelvis demonstrating hepatic masses and a large right testicular mass, suspicious for primary testicular malignancy. On return evaluation, he was noted to have tachycardia with HR 165, mild scleral icterus, tenderness to palpation of right upper quadrant, abdominal pain and a right scrotal mass (5x5 cm). CBC revealed; WBC 12.0 k/uL (n: 4-10.8), AST: 428 u/L (n: 3-34); ALT: 176 u/L (n: 15-41); total bilirubin: 6.3 mg/dL (n: 0.2-1.3), TSH <0.005 uIU/mL (n: 0.4-4.0) and FT4 5.02 ng/dL (n: 0.7-1.4). Clinical scenario was consistent with thyrotoxicosis concerning for thyroid storm (Burch-Wartofsky Point Scale: 50) requiring intensive care for which he was transferred to our institution. Thyroid US revealed increased thyroid vascularity without nodularity. Laboratory workup revealed negative TG Ab, Anti-TPO Ab, TRAb, and TSIG. Conversely, TBG was elevated at 31.2 mcg/ml (n: 13-30). Initial hCG level was obtained as 6,074. After re-testing with dilution was specifically requested, initial hCG was corrected to 6,760,713. Oncologic workup confirmed diagnosis of hCG producing testicular choriocarcinoma with liver and lung metastases. On admission, he was started on oral methimazole and propranolol as well as intravenous steroids which led to marked symptomatic improvement and normalization of FT4 to 1.37 allowing for discontinuation of antithyroid medication on 7th day of hospitalization. He completed 1 cycle of cisplatin/etoposide and experienced marked reduction of his hCG level to 951,460 which correlated with improvement of his TFTs and resolution of his hyperthyroid symptoms.Conclusion:A low threshold of suspicion should be maintained for the possibility of hyperthyroidism in patients with suspected testicular choriocarcinoma, particularly in the context of recent iodinated contrast imaging. If the clinical picture does not support a primary etiology of hyperthyroidism and hCG is not concordantly elevated, re-assessment of hCG by dilution should be considered as hCG assay is also subject to prozone (hook) effect. Hyperthyroidism should be actively managed and closely monitored as response to treatment can be rapid.

Результативность применения методов ВРТ для лечения бесплодия у мужчин 40 лет и старше с обструктивной азооспермией

to evaluate the efficacy of ART methods to treat infertility in men with obstructive azoospermia. The results of treatment of infertile couples using ART methods during the period from 2009 to 2017 were analyzed. A total of 18 married couples with obstructive azoospermia in men were included in the main group. The control group consisted of 59 married couples in which men had spermatozoa in the ejaculate. Both groups were comparable in age, concomitant gynecological pathology in female partner, protocols of superovulation, fertilization method, days of transfer and the number of transferred embryos into the uterine cavity. The results were evaluated by pregnancy rate (according to the results of determining the level of the -subunit of human chorionic gonadotropin), clinical pregnancy rate (according to the results of the first ultrasound), the number of birth and the number of living children. Pregnancy rate in the main group was 55.6%, compared to 35.6% in the control group (2 with Yeats correction = 1531, p=0.217), while clinical pregnancy rate was 44.4% and 32.2%, respectively (2with Yeats correction = 0.450, p=0.503). In the main group, there were 6 births and 8 children were born (4 with one fetus and 2 twin). In the control group, there were 14 births (2 with Yeats correction=0.168, p=0.683 in comparison with the main group) and 19 children were born (12 one fetus, 2 twins, 1 triplets). The high rates obtained in the main group can be explained by the fact that the obstructive azoospermia doesnt have such a pronounced negative influence on spermatozoa as a non-obstructive azoospermia, and, possibly, as severe oligozoospermia. Our data have convincingly established the efficiency of testicular biopsy for the treatment of infertility in men with azoospermia. In addition, spermatozoa obtained from these patients, are suitable for fertilization.

Twin pregnancies concieved by assisted reproduction - early prediction of preterm birth

Background/Aim. Twins conceived by assisted reproduction techniques (ART) are the most susceptible for perinatal complications. The aim of this study was to examine the role of prenatal noninvasive fetal screening of the first and second trimester in prediction of delivery time of ART conceived twins. Methods. Prospective cohort study of all ART conceived twin pregnancies was conducted at the Clinic for Obstetrics and Gynecology, Clinical Center of Serbia, during the period from January 1, 2016 to December 31, 2017. In the 12th gestational week (GW) twins crown-rump lenght (CRL) and thickness nuchal translucency (NT) were measured ultrasonographically. Moreover, serum levels of beta subunit of human chorionic gonadotropin (? hCG) and pregnancy-associated plasma protein A (PAPPA) were assessed. In the 17th GW twins biparietal diameter (BPD), abdominal circumference (AC) and femur length (FL) were determined ultrasonografically. Additionally, ? hCG, alphafetoprotein (AFP), estriol (E3) and inhibin (INH) were measured in mothers serum. The GW of delivery was noted for each pregnancy. Results. Study included 100 pregnant women with mean age 35.44 ? 5.82. In the examined sample of ART conceived twins significantly more (51%) were delivered in term (? 35 GW) (p = 0.001). Delivery time correlated negatively with NT and first trimester ? hCG serum levels, while it correlated positively with FL of the smaller twin, second trimester ? hCG, AFP and E3 concentrations. According to obtained model for prediction of delivery time in ART conceived twin pregnancies based on first trimester diagnostic tests the significant predictors were PAPPA and ? hCG in the 12th GW as well as NT of the first larger twin. Nevertheless, reliability (sensitivity 50%?75%, specificity 30%?40%) of these diagnostic tests was moderate. Conclusion. Prenatal noninvasive fetal screening of the first and second trimester (ultrasonography and laboratory testing) can be used for prediction of delivery time of ART conceived twins.

Significance of the routine first-trimester antenatal screening program for aneuploidy in the assessment of the risk of placenta accreta spectrum disorders.

Objective To select a group at high risk of placenta accreta spectrum disorders (PAS) based on the data of serum screening in the first trimester. Methods A retrospective analysis of 48 patients with abnormal placental location (AP), including placenta previa (PP) only (n = 23) and PP and PAS (n = 25), was performed. Additionally, the AP group was divided depending on the blood loss volume: not higher than 1000 mL (LBL) (n = 29) and higher than 1000 mL (HBL) (n = 19); diagnostic term of PAS by ultrasound, data pregnancy-associated plasma protein-A (РAРР-A) and free β subunit of human chorionic gonadotropin (free β-hCG) multiple of median (MоM) at 11+0-13+6 weeks of gestation were evaluated. Serological markers were compared with the data of 39 healthy pregnant women with scar after previous cesarean section and normal placental location (control). Results The mean gestation at diagnostic term of PAS was 29 weeks. PAPP-Р MоM [mean (M) ± standard deviation (SD)] was: in controls, 1.07 ± 0.47; in the AP group, 1.59 ± 0.24; in PP, 1.91 ± 1.52; in PAS, 1.30 ± 0.85; in LBL, 1.37 ± 1.20; in HBL, 1.91 ± 1.24. The difference between control/AP, control/PP, control/PAS, PP/PAS, control/LBL, control/HBL and LBL/HBL was Р = 0.256, 0.145, 0.640, 0.311, 0.954, 0.025 and 0.09, respectively. Free β-hCG MoM (M ± SD) was: in controls, 1.08 ± 0.69, in AP, 1.31 ± 0.96; in PP, 1.46 ± 0.19; in PAS, 1.16 ± 0.65; in LBL, 1.30 ± 0.06; in HBL, 1.32 ± 0.78. Comparison of free β-hCG AP with controls and between subgroups did not reveal a significant difference. Conclusion Underestimation of PAS risk factors in pregnant women with AP leads to late diagnostics of pathology only in the third trimester. The assessment of the РAРР-A level in the first trimester may be helpful for the early prognosis of pathological blood loss at delivery for pregnant women with AP and for forming the high-risk group for PAS.

Diagnosis of pregnancy based classification of embryo culture medium samples by infrared spectrometry and chemometrics

Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy coupled with chemometric procedures was utilized to examine embryo culture medium (ECM) samples in in vitro fertilization (IVF) to differentiate between positive and negative pregnancy.Principal component analysis (PCA) method was successfully applied to mid-IR spectra as outlier detection by application of Hotelling T2 statistic procedure. Unsupervised and supervised pattern recognition techniques, such as hierarchical agglomerative cluster algorithm (HACA), soft independent modeling of class analogy (SIMCA) as a linear supervised pattern recognition technique, binned nearest neighbors (BNN) as a local classifier and counter-propagation artificial neural networks (CP-ANN) as a non-linear technique were used in spectral data analysis for classification and differentiation. Also, the genetic algorithm (GA) as the variable reduction was employed to develop the diagnostic model.A total of 46 ECM samples were examined in the 3000–1000 cm−1 spectral region. Classification efficiency parameters including accuracy (ACC), error rates (ER), sensitivity (Sens), specificity (Spec) and non-error rate (NER) were calculated. Classification ACC of 92.00% and ER of 8.300% was acquired using GA-BNN algorithm, while GA-CP-ANN and GA-SIMCA algorithms provided 93.00% and 5.00% of ACC and ER for the test set, respectively. The results of this study presented that the GA-SIMCA and the GA-CP-ANN chemometric approaches using the infrared data, achieved acceptable results. Also, both of methods could provide the Sens rate of 100.00% and 91.00%, and the Spec rate of 91.00% and 100.00% for positive pregnancy samples (class 1) and negative ones (class 2) in prediction test, respectively.In general, the main advantages of the proposed method could be represented as a reliable, fast, simple, and accurate method for the classification and discrimination of the ECM samples based on their serum beta- subunit human chorionic gonadotropin (β-hCG) levels after embryo transfer (ET) about 15 days later.

Unusual Presentation of Metastatic Cervical Squamous Cell Carcinoma with Serum Positive Beta Human Chorionic Gonadotropin.

Abstract We present a case of a 30-year-old female who presented with one month of worsening dyspnea. On admission she was having pleuritic chest pain with associated cough and worsening dyspnea. CTA showed a moderate sized pleural effusion with two hypodensities noted in the liver. Patient received several thoracenteses and had abdominal distension that required paracentesis, which showed transudative fluid initially. There was a noted supraclavicular lymph node, however the patient refused lymph node biopsy. Retroperitoneal lymph node, which was seen on CT abdomen, was eventually biopsied which showed metastatic carcinoma with squamoid differentiation with unknown primary. Beta subunit of human chorionic gonadotropin (b-HCG) was rechecked for the biopsy and was mildly elevated to 33. The patient refused gynecological evaluation, pelvic ultrasound revealed a distended endometrial cavity with heterogeneous contents and a complex left adnexal cyst. Pelvic MRI noted a large cervical mass (4.6x4.5x3.8cm) with parametrial invasion. Subsequently her status declined, and she was intubated for hypoxic respiratory failure. Patient unfortunately passed away. Autopsy confirmed metastatic cervical cancer with significant tumor burden as evidence of &gt;80% of the liver with tumor. Although the patient’s pap smear previously did not culture for HPV, the lymph node biopsy stained positive with Pap stain and shown that the carcinoid cells were most affected by HPV. Later is was found that 3.5 years prior the patient had a Pap smear positive for low-grade squamous intraepithelial lesion however was lost to follow up. Although there have been studies that have examined cervical cancer and the intracellular expression of b-hCG, serum b-hCG is not known to be elevated in squamous cell carcinoma of the cervix. For women presenting with wide spread disease, gynecological malignancies should be ruled out regardless of age.

Tumor expression of human chorionic gonadotropin beta mRNA and prognosis of prostate cancer treated by radical prostatectomy

The beta subunit of human chorionic gonadotropin (hCGβ) is encoded by six genes (CGB) classified as type I and type II. CGB mRNA is produced in large amounts by trophoblastic tissues and in small amounts by several cancerous tissues including prostate cancer and by a few benign tissues, including the prostate. Quantitative reverse-transcription polymerase chain reaction (RT-qPCR) was used to study the expression levels of all CGB mRNAs together (total CGB mRNA) and the two types of CGB mRNA separately in non-cancerous (n = 74) and cancerous prostatic tissue obtained by radical prostatectomy (n = 193). RNA was isolated from formalin-fixed paraffin-embedded (FFPE) samples and mRNA levels of CGB were correlated with disease-specific survival. Total CGB mRNA concentrations were significantly lower (p < .0001) in cancerous than non-cancerous prostatic tissue. Separate analysis of type I CGB and type II CGB mRNA showed that both type I CGB (p < .0001) and type II CGB mRNA (p = .007) are lower in cancerous tissue than in non-cancerous tissue. Low type II CGB mRNA level in cancerous tissue was associated with shorter cancer-specific survival (p = .001) of prostate cancer patients treated by radical prostatectomy.

The value of an initial drop in human Chorionic gonadotropin levels in predicting a response to methotrexate in women with low-risk gestational trophoblastic neoplasia.

The early identification of patients who are being treated for low-risk gestational trophoblastic neoplasia (LRGTN) with single-agent chemotherapy, who are at high risk of developing chemoresistance, is of crucial importance. The aim of our research was to evaluate the pretreatment beta subunit of human chorionic gonadotropin (βhCG) concentration and its decrease after the administration of the first course of methotrexate (MTX) in predicting later chemo-resistance to single-agent chemotherapy. A total of 46 patients diagnosed with LRGTN treated with a 5-day methotrexate (MTX) regimen were retrospectively studied. 24 of the patients were successfully cured with only MTX therapy (MTX group). The disease was considered resistant in the remaining 22 patients who, after MTX therapy, required further chemotherapy with an EMA/CO regimen (EMA/CO group). To compare changes in the βhCG concentrations between the two courses of treatment (and the two groups), we calculated the percentage of decline. We determined the specificity and sensitivity of the initial βhCG level and its percentage decline, as a potential predictor of the need for a future EMA/CO regimen. For diagnostic purposes, βhCG levels were measured before the first and second administrations of MTX with a commercial ELISA kit. In the EMA/CO group, we found the initial βhCG level before the first MTX dose was higher (median = 6275 mIU/mL, range: 21.53-192.610.0 mIU/mL) than in the MTX group (median = 532 mIU/mL, range: 56.5 mIU/mL-360.397.0 mIU/mL) (p = 0.034, Mann-Whitney test). The percentage decreases in the βhCG values relative to the initial concentrations were higher in the MTX group (median decrease = 82.7%, range: from 13.3% to 99.9%) than in the EMA/CO group (median de- crease = 71.1%, range: from an increase of 56.1% to a decrease of 97.1%) (p = 0.0079, Mann-Whitney test). An analysis of the ROC curves implied optimal cutoff values for the initial βHCG (6054 IU, sensitivity = 55%, specificity = 86%) and the percentage change in βhCG levels (decrease by 76.5%, sensitivity = 72%, specificity = 71%). Women with initially higher βhCG levels have a greater risk of developing MTX chemo resistance. It would be advantageous to consider administering an EMA/CO regimen in women with LRGTN when their initial βhCG levels are greater than 6000.

Role of Surgery in the Management of Gestational Trophoblastic Neoplasia

Gestational trophoblastic neoplasia (GTN) is now one of the most curable gynaecologic malignancies owing to effective chemotherapy and sensitive tumour marker β hCG (beta subunit of human chorionic gonadotropin). The objective of this study was to evaluate the role of adjuvant surgical procedures in the management of GTN. A retrospective review was done of available records of all GTN cases managed at our regional cancer centre from 2009 to 2017. Thirteen out of 134 patients required some surgical intervention. The number of surgical procedures done was 15. Of a total of 134 patients, 13 (9.7%) patients required surgical intervention. Thirteen patients underwent 15 surgical procedures. Two patients had more than one surgery—hysterectomy and pulmonary resection. Seven surgical procedures were done for the control of haemorrhage—one emergency hysterectomy with bilateral internal iliac ligation, one internal iliac ligation, two internal iliac embolisation, two uterine artery embolisation, and vaginal sutures in one patient. Six surgeries were done in four patients for excision of chemoresistant disease—hysterectomy in two patients and hysterectomy and pulmonary resection in two patients. Hysterectomy with BPLND was done in a case of PSTT. Small bowel resection and anastomosis were done in one patient with intestinal obstruction. Though chemotherapy is the mainstay of treatment in GTN, surgery may be necessary as a life-saving procedure in case of haemorrhage or to achieve remission in chemoresistant disease. High-risk GTN cases must be managed at tertiary care centres under care of a multidisciplinary team.

The transgenic expression of the β-subunit of human chorionic gonadotropin influences the growth of implanted tumor cells.

The beta subunit of human chorionic gonadotropin (βhCG) is secreted by various tumors, and its presence associated with poor prognosis. Though exogenous hCG elicits the synthesis of molecules associated with angiogenesis, invasion, immune suppression and chemoresistance from responsive tumor cells in vitro, the influence of cell-extrinsic βhCG on tumorigenesis in vivo has not been adequately explored. Female C57BL/6−/− × FVBβhCG/− F1 transgenic mice demonstrated ovarian hyperplasia and pituitary adenomas; transcripts of hCG-driven, tumor-associated molecules were heightened in the pituitary. Upon the implantation of Lewis Lung Carcinoma cells (murine lung tumor cells derived from C57BL/6 mice) in transgenic mice, tumor incidence and volume were enhanced, and increased transcription and expression of hCG-driven, tumor-associated molecules was observed in excised tumors. While treatment of these mice with Cabergoline (a potent dopamine receptor agonist) had no significant effects, ovariectomy resulted in a reduction in the lag phase, accompanied by an increase in tumor incidence and volume upon Lewis Lung Carcinoma cell implantation. In tumors derived from Lewis Lung Carcinoma cell-implanted ovariectomized, transgenic mice, the transcription and expression of hCG-driven, tumor-associated molecules remained elevated and enhanced animal mortality was observed. Cell-extrinsic βhCG can therefore induce pro-tumorigenic effects in vivo (even on tumor lineages not part of the reproductive axis), with ovarian products mediating an ameliorating influence.

Optimization of regional median equations of prenatal screening markers for trisomy 21 in a Chinese population.

To establish gestational age-specific and body weight-specific mid-trimester normal median equations for the prenatal serum markers α-fetoprotein (AFP), free β subunit human chorionic gonadotropin (fβHCG), and unconjugated oestriol (uE3) for a Chinese population; to compare and replace the median equations built in LifeCycle software; to evaluate the effect of equations used for gestation correction on estimating risk in Down's syndrome, Edward's syndrome, and neural tube defect (NTD).A total of 353,065 cases of prenatal screening data of pregnant women were screened by 13 prenatal screening institutions in China. The local median equations of each institution and the large data were fitted by the least square regression, and then the difference was compared between large data equations and local median equations. The applicability of the localized median equations was evaluated by the determination coefficient. Based on the established median equations, multiples of median (MoM) of each values were calculated and compared with the latest Down's syndrome quality assurance support service (DQASS).There is no significant difference between the local median equations of each institution and the large sample median equations, which are various from LifeCycle built-in median equations. Besides, the determination coefficient of localized median equations are >0.99. 97.0% MoM medians obtained by using local median equations are consistent with latest standard of DQASS.The median established by large sample data represents the median level of a Chinese population, and can be used to replace the software built-in median equations to achieve better screening results.

B Subunit of Human Chorionic Gonadotropin Promotes Tumor Invasion and Predicts Poor Prognosis of Early-Stage Colorectal Cancer

Background/Aims: It is well established that many non-trophoblastic tumors secrete HCG (human chorionic gonadotropin) and that such secretion is correlated with the poor prognosis of tumor patients. This study aims to analyze the correlation between β-HCG expression and outcome of colorectal cancer (CRC) and understand its role in CRC pathology Methods: We detected the mRNA and protein expression of β-HCG in human CRC tissues with RT-qPCR and immunohistochemistry, and we compared the clinical-pathological characteristics, prognosis and progression between the β-HCG positive and negative groups. We also generated CRC cell lines with β-HCG over-expression as well as β-HCG stable knockout, and evaluated cell function and mechanism in vitro and in vivo. Results: Fifty out of 136 CRC patients (37%) expressed β-HCG at the invasive front. Clinical-pathological data showed that β-HCG was positively correlated with Dukes staging (P=0.031) and lymph node metastasis (P=0.012). Survival analysis suggested that the patients with high expression of β-HCG had poorer prognosis than those with low β-HCG expression (P=0.0289). β-HCG expression level was also positively correlated with tumor invasion in early-stage CRC patient tissues (P=0.0227). Additionally β-HCG promoted the migration and invasion of CRC in vitro and in vivo but had no effect on the proliferation of tumor cells. Conclusion: Our study demonstrated that β-HCG was ectopically expressed in the CRC patients and its high expression correlated with poor prognosis of early-stage CRC. Additionally it worked as an oncogene that promotes the migration and invasion of CRC by epithelial-mesenchymal transition (EMT).

Pulmonary Metastatic Choriocarcinoma in a Patient with Ectopic Pregnancy

Background & aim: Gestational trophoblastic tumor (GTT) most commonly follows a molar pregnancy. In fact, it can occur following gestational events such as induced or spontaneous abortion, ectopic pregnancy, and term pregnancy. Case report: In this study, we present the case of a patient with ectopic pregnancy who was treated with a single dose of methotrexate (MTX). The maximum titer of beta subunit of human chorionic gonadotropin (BHCG) was 402. Work up of occult metastatic GTT was carried out following MTX therapy, due to elevated BHCG titer. In the positron emission tomography (PET) scan, a 17-mm lesion was detected in the right lung and treated via thoracotomy resection and adjuvant chemotherapy. Within an 18-month follow up, the patient did not reveal any symptoms and the BHCG titer level did not increase. Conclusion: Findings of this study revealed that after MTX therapy for ectopic pregnancy patients need to be followed up. Moreover, lack of BHCG titer decline, even in low tittering after treatment with MTX, can be related to GTT tumors or inadequate treatment for ectopic pregnancy.

MicroRNA-371a-3p as informative biomarker for the follow-up of testicular germ cell cancer patients

Purposeα-fetoprotein (AFP) and human chorionic gonadotropin subunit beta (B-HCG) are informative serum biomarkers for the primary diagnosis and follow-up of testicular germ cell cancer (TGCC) patients. About 20% of TGCC patients with a non-seminoma (NS) and about 80% with a seminoma (SE) are, however, negative for these biomarkers. Embryonic stem cell microRNAs (miRs) may serve as promising alternative serum biomarkers. Here we investigated a retrospective series of serum samples from selected TGCC patients who developed a relapse in time to test the possible additional value of the serum-based ampTSmiR test compared to the conventional serum-based protein biomarkers for follow-up.MethodsWe investigated 261 retrospective serum samples of six selected fully evaluated TGCC patients with a proven relapse using the ampTSmiR test for miR-371a-3p, miR-373-3p, and miR-367-3p and compared the results to those of the conventional protein biomarkers.ResultsAt primary diagnosis, elevated serum B-HCG, AFP and LDH levels were found to be informative in 4/6, 3/6 and 3/6 patients, respectively. At primary diagnosis the levels of miR-371a-3p and miR-373-3p were elevated in 4/4, and miR-367-3p in 3/4 patients. For two cases no starting serum sample was available for retrospective miR analysis. Residual disease (overlooked by histopathological examination) was detected in one case by miR-371a-3p only. The miR-371a-3p level was increased in one patient two months before detection of an intracranial metastasis. B-HCG was informative in 3/4 and the ampTSmiR test in 4/4 patients with a relapse or residual disease. None of the biomarkers were informative for the detection of residual mature teratoma.ConclusionsThe ampTSmiR test is more sensitive than the conventional TGCC protein biomarkers for the detection of residual disease and relapse, excluding mature teratoma.

Analysis of Down syndrome failed to be diagnosed after prenatal screening: A multicenter study.

To analyze the characters of Down syndrome (DS) who failed to be diagnosed after prenatal screening and hope to be able to improve the programs of prenatal screening and reduce the missed diagnosis of DS. In this multicenter study, we collected the missed cases from 3 prenatal diagnosis centers and analyzed their characters. A total of 126 DS babies failed to be diagnosed after prenatal screening. Their mothers accepted the prenatal screening in second trimester. We collected the mothers’ blood and detected the levels of alpha-fetoprotein (AFP) and the free beta subunit of human chorionic gonadotropin (fβhCG) by time-resolved fluoroimmunoassay. The values were also presented as multiples of the median (MoM) and determined the risk of carrying a fetus with DS by Wallace LifeCycle Elipse analysis software. Compared with normal control group, the level of fβhCG and hCG MoM were dramatically increased, while AFP and AFP MoM were decreased. The area under the receiver-operating-characteristic curve of trisomy 21 was 0.8387 for hCG-MoM and AFP-MoM testing. The sensitivity, specificity, positive predictive value, and negative predictive value were 84.6%, 74.8%, 75.4%, and 83.6%, respectively. Meanwhile, the prediction mode was “0.39957 + 1.90897∗HCG-MOM −3.32713∗AFP-MOM”. It was worthwhile noting that the risk of 65.9% DS missed diagnosis group were higher than 1/1000, 92.9% higher than 1/3000. However, 72.5% cases in normal control group were lower than 1/3000. Only 9.2% mothers would be higher than the value of risk in 1/1000. The prediction mode of hCG MoM and AFP MoM might be able to help us reduce the missed diagnosis. It is also necessary to adjust more reasonable range of noninvasive prenatal testing with further clinical researches.

External Quality Assessment of First-Trimester Prenatal Biochemical Screening in China.

Free β subunit of human chorionic gonadotropin (free β-hCG) and pregnancy-associated plasma protein A (PAPP-A) are two important biomarkers in first-trimester prenatal screening. This study intended to reflect their analytical performance in clinical laboratories and main platforms of the 2015 External Quality Assessment (EQA) scheme for the first-trimester biochemical screening in China. Ten lyophilized EQA samples, divided into two sets and analyzed in two cycles 20151 and 20152, were distributed to each participant in 2015. Satisfactory performance was defined as scores more than 80 of acceptable results within the evaluation criterion of ± 30%. The robust coefficient of variability (CV) of each sample was calculated by analytes and mainstream platforms. The chi-square (2) test and the Mann-Whitney test were respectively used to compare the acceptable performance and the robust CV between two analytes, as well as two mainstream platforms. A total of 142 laboratories were enrolled in this EQA scheme. For free β-hCG and PAPP-A, the number of effective results were 1330 and 1355, respectively, and the overall acceptable rates of results were 95.11% and 92.32%, respectively. For cycle 20151 and 20152, the acceptable rates were respectively 92.59% and 96.19% for free β-hCG and 89.78% and 94.78% for PAPP-A. The 2 test showed acceptable performance differed significantly between the two analytes, as well as two platforms for PAPP-A. Significant difference of the robust CV in different analytes and platforms was demonstrated by Mann-Whitney test. Greater than 92% of results were acceptable. However, continuous improvement and further research of this EQA scheme is in process.