Difference between revisions of "Talk:Abnormal Development - Hydatidiform Mole"
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===Serum Human Chorionic Gonadotropin Normogram for the Detection of Gestational Trophoblastic Neoplasia===
===Serum Human Chorionic Gonadotropin Normogram for the Detection of Gestational Trophoblastic Neoplasia===
Revision as of 19:48, 25 July 2017
Establishment and characterization of cell lines derived from complete hydatidiform mole
Int J Mol Med. 2017 Jul 14. doi: 10.3892/ijmm.2017.3067. [Epub ahead of print]
Yamamoto E1, Niimi K1, Kiyono T2, Yamamoto T3, Nishino K1, Nakamura K1, Kotani T1, Kajiyama H1, Shibata K1, Kikkawa F1.
Gestational trophoblastic diseases (GTDs) are a group of diseases characterized by abnormal cellular proliferation of atypical trophoblasts. A hydatidiform mole is an abnormal pregnancy caused by genetic fertilization disorders, and it can be classified as a complete hydatidiform mole (CHM) or a partial hydatidiform mole. The aim of this study was to establish cell lines from CHMs and to characterize the cells for future studies concerning GTD. HMol1-2C, HMol1-3B, HMol1-8 and HMol3-1B were established from primary cultures of CHM explants following the introduction of different combinations of genes including human telomerase reverse transcriptase (hTERT), a mutant form of CDK (CDK4R24C), cyclin D1, p53C234, MYC and HRAS. HMol1-2C, HMol1-3B, and HMol3-1B were confirmed to originate from trophoblasts of androgenic, homozygous CHMs. These three cell lines exhibited low human chorionic gonadotropin secretion, low migration and invasion abilities, and the potential to differentiate into syncytiotrophoblastic cells via forskolin treatment. These results suggest that these cells exhibit characteristics of trophoblastic cells, especially cytotrophoblastic cells. HMol1-8 was found to consist of diploid cells and originated from maternal cells, suggesting that they were derived from decidual cells. In conclusion, we successfully established three cell lines from CHMs by introduction of hTERT and other genes. Analysis revealed that the genetic origin of each cell line was identical with that of the original molar tissue, and the cell lines exhibited characteristics of trophoblastic cells, which are similar to undifferentiated cytotrophoblasts. PMID: 28713902 DOI: 10.3892/ijmm.2017.3067
Serum Human Chorionic Gonadotropin Normogram for the Detection of Gestational Trophoblastic Neoplasia
Int J Gynecol Cancer. 2017 May 12. doi: 10.1097/IGC.0000000000000966. [Epub ahead of print]
Eysbouts Y1, Brouwer R, Ottevanger P, Massuger L, Sweep F, Thomas C, van Herwaarden A.
OBJECTIVE: The aim of this study was to develop a serum human chorionic gonadotropin (hCG) normogram for both uneventful complete and partial hydatidiform moles in the first-trimester ultrasound era. METHODS: An hCG normogram for both complete and partial hydatidiform moles was constructed, based on 639 patients with uneventful serum hCG regression after evacuation between 1990 and 2014. Serum hCG was measured by an in-house-developed radioimmunoassay, detecting both intact hCG and free β-subunit. It has been in use for all serum measurements sent to the Dutch Central Registry for Hydatidiform Moles since 1977. RESULTS: Since introduction of routine first-trimester ultrasonography, lower pre-evacuation and follow-up serum hCG concentrations were observed. When compared with complete hydatidiform moles, patients with a partial hydatidiform mole had significantly lower pre-evacuation serum hCG concentration (median, 4400 and 875 ng/mL, respectively; P < 0.001) and earlier hCG normalization (median, 7 and 6 weeks, respectively; P < 0.001) but higher gestational age (mean, 11.5 and 13.0 weeks, respectively; P < 0.001). For both complete and partial hydatidiform moles, 95% of patients reached normal serum hCG concentrations within 14 weeks after evacuation. CONCLUSIONS: A normogram for the detection of gestational trophoblastic neoplasia was developed for complete and partial hydatidiform moles. Although interesting from a scientific perspective, the small divergence in hCG regression between complete and partial hydatidiform moles will be of little importance in clinical practice, as actual differences in regression will encompass only days. To promote clarity and unity in daily practice, we therefore propose a combined normogram to be used as a reference guideline for follow-up after evacuation of a hydatidiform mole. This normogram will be compliant with patients in today's clinical practice.
PMID 28498241 DOI: 10.1097/IGC.0000000000000966
Gestational Trophoblastic Disease: Clinical and Imaging Features
Radiographics. 2017 Mar-Apr;37(2):681-700. doi: 10.1148/rg.2017160140.
Shaaban AM1, Rezvani M1, Haroun RR1, Kennedy AM1, Elsayes KM1, Olpin JD1, Salama ME1, Foster BR1, Menias CO1.
Gestational trophoblastic disease (GTD) is a spectrum of both benign and malignant gestational tumors, including hydatidiform mole (complete and partial), invasive mole, choriocarcinoma, placental site trophoblastic tumor, and epithelioid trophoblastic tumor. The latter four entities are referred to as gestational trophoblastic neoplasia (GTN). These conditions are aggressive with a propensity to widely metastasize. GTN can result in significant morbidity and mortality if left untreated. Early diagnosis of GTD is essential for prompt and successful management while preserving fertility. Initial diagnosis of GTD is based on a multifactorial approach consisting of clinical features, serial quantitative human chorionic gonadotropin (β-hCG) titers, and imaging findings. Ultrasonography (US) is the modality of choice for initial diagnosis of complete hydatidiform mole and can provide an invaluable means of local surveillance after treatment. The performance of US in diagnosing all molar pregnancies is surprisingly poor, predominantly due to the difficulty in differentiating partial hydatidiform mole from nonmolar abortion and retained products of conception. While GTN after a molar pregnancy is usually diagnosed with serial β-hCG titers, imaging plays an important role in evaluation of local extent of disease and systemic surveillance. Imaging also plays a crucial role in detection and management of complications, such as uterine and pulmonary arteriovenous fistulas. Familiarity with the pathogenesis, classification, imaging features, and treatment of these tumors can aid in radiologic diagnosis and guide appropriate management. ©RSNA, 2017.
PMID 28287945 DOI: 10.1148/rg.2017160140
Radiographically occult pulmonary metastases from gestational trophoblastic neoplasia
Radiol Case Rep. 2017 Feb 10;12(2):292-294. doi: 10.1016/j.radcr.2017.01.007. eCollection 2017 Jun.
Hong T1, Hills E1, Aguinaga MDP1.
Gestational trophoblastic neoplasia (GTN) is a spectrum of diseases including partial and complete hydatidiform moles, placental site trophoblastic tumor, and choriocarcinoma. One of the most important considerations is recognition of the possibility of GTN after molar pregnancy or even normal pregnancy. It is common practice to use chest x-ray for the detection of pulmonary metastasis. Computed tomography imaging of the lungs is ordered if lung lesions are noted on chest x-rays. However, understanding the limitations of chest x-rays is important for detecting smaller pulmonary lesions. We present a patient with GTN and pulmonary metastasis after having received 2 negative chest x-rays. KEYWORDS: Gestational trophoblastic neoplasia; Molar pregnancy; Pulmonary metastasis PMID 28491173 PMCID: PMC5417626 DOI: 10.1016/j.radcr.2017.01.007
Risk of recurrent molar pregnancies following complete and partial hydatidiform moles
Hum Reprod. 2015 Jul 22. pii: dev169. [Epub ahead of print]
Eagles N1, Sebire NJ2, Short D1, Savage PM1, Seckl MJ3, Fisher RA4.
STUDY QUESTION: What is the risk of further molar pregnancies for women with one or more hydatidiform moles (HM) in relation to molar subtype. SUMMARY ANSWER: Women with a complete hydatidiform mole (CM) have a 1 in 100 and 1 in 4 risk of further CM after one or two consecutive CM, respectively, while women with a partial hydatidiform mole (PM) have only a small increase in risk for further molar pregnancies. WHAT IS KNOWN ALREADY: Women with a molar pregnancy have an increased risk of further HM. A small subgroup of women with recurrent HM has an autosomal recessive condition, familial recurrent hydatidiform moles (FRHM), that predisposes them to molar pregnancies. STUDY DESIGN, SIZE, DURATION: A retrospective study of subsequent pregnancies in 16 000 women registered at a centralized referral centre, with a CM or PM, between 1990 and 2009. PARTICIPANTS/MATERIALS, SETTING, METHODS: One hundred and sixty-six women with two or more molar pregnancies were identified from electronic records and patient notes. Histopathological features of all molar tissue were reviewed in these cases and genotyping performed where diagnosis was not possible on the basis of histopathological features alone. In addition, genotyping of molar tissue was performed in all cases of women with three or more CM to establish whether the tissue was diploid and biparental or androgenetic. MAIN RESULTS AND THE ROLE OF CHANCE: This study confirms an increased recurrence risk of ∼1% for a second molar pregnancy and in addition that this risk is associated with CM rather than PM. The data further indicate that the risk of a third HM is associated almost exclusively with CM and enabled an estimate that 1 in 640 women registered with a CM has the rare condition FRHM. The study also found that there was no significant difference between the risk of developing gestational trophoblastic neoplasia (GTN) for typical sporadic CM and the diploid biparental CM associated with FRHM (GTN; proportion difference 0.05, Z = 0.87, P = 0.29). LIMITATIONS, REASONS FOR CAUTION: While pathology was reviewed for all women with two or more molar pregnancies, not all cases registered underwent central review particularly those women registered in the early 1990s. It is therefore possible that the total number of CM and PM may differ slightly from that stated. While women were followed for a minimum of 5 years, it is possible that some women may subsequently have further molar pregnancies that will not have been included in the present study. WIDER IMPLICATIONS OF THE FINDINGS: This is the largest study to date on recurrence for molar pregnancies, and as such provides the most detailed information so far regarding the risk of further molar pregnancies for women with a PM or CM. Furthermore, the data provide new insights into the incidence of the rare autosomal recessive condition, FRHM, important information for counselling women with molar pregnancies. STUDY FUNDING/COMPETING INTERESTS: No competing interests declared. No funding was obtained for this study. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: email@example.com. KEYWORDS: NLRP7; complete hydatidiform mole; gestational trophoblastic neoplasia; partial hydatidiform mole; recurrent hydatidiform moles PMID 26202916
NLRP7, Involved in Hydatidiform Molar Pregnancy (HYDM1), Interacts with the Transcriptional Repressor ZBTB16
PLoS One. 2015 Jun 29;10(6):e0130416. doi: 10.1371/journal.pone.0130416.
Singer H1, Biswas A1, Nuesgen N1, Oldenburg J1, El-Maarri O1.
Mutations in the maternal effect gene NLRP7 cause biparental hydatidiform mole (HYDM1). HYDM1 is characterized by abnormal growth of placenta and lack of proper embryonic development. The molar tissues are characterized by abnormal methylation patterns at differentially methylated regions (DMRs) of imprinted genes. It is not known whether this occurs before or after fertilization, but the high specificity of this defect to the maternal allele indicates a possible maternal germ line-specific effect. To better understand the unknown molecular mechanism leading to HYDM1, we performed a yeast two-hybrid screen against an ovarian library using NLRP7 as bait. We identified the transcriptional repressor ZBTB16 as an interacting protein of NLRP7 and verified this interaction in mammalian cells by immunoprecipitation and confocal microscopy. Native protein analysis detected NLRP7 and ZBTB16 in a 480kD protein complex and both proteins co-localize in the cytoplasm in juxtanuclear aggregates. HYDM1-causing mutations in NLRP7 did not show altered patterns of interaction with ZBTB16. Hence, the biological significance of the NLRP7-ZBTB16 interaction remains to be revealed. However, a clear effect of harvesting ZBTB16 to the cytoplasm when the NLRP7 protein is overexpressed may be linked to the pathology of the molar pregnancy disease.
Two cases of complete hydatidiform mole and coexistent live fetus
J Prenat Med. 2013 Jan;7(1):1-4.
Vimercati A, de Gennaro AC, Cobuzzi I, Grasso S, Abruzzese M, Fascilla FD, Cormio G, Selvaggi L. Source Obstetrics, Gynaecology and Neonatology, University of Bari, Bari, Italy.
The aim of this study was to report the clinical features, management, and outcome of complete hydatidiform mole with a coexisting viable fetus. Two cases are reported. In both cases ultrasound examination demonstrated a normally growing live fetus alongside a normal placenta and an additional intrauterine echogenic mass with features of hydatidiform mole. The hCG levels were significantly increased and fetal karyotypes were normal. A cesarean section performed at 28 weeks' gestation in the first case and at 26 weeks' gestation in the second one resulted in the delivery of live normal infant and two adjoining placentas in both cases. Microscopic examination of the abnormal placentas confirmed complete hydatidiform mole. The babies did well and serial maternal serum hCG levels showed a declining trend and were undetectable by a few months after delivery. Continuation of a twin pregnancy with complete hydatidiform mole (CHMF) is an acceptable option. There is, although, an increased risk of developing maternal and fetal complications. Close surveillance of an ongoing pregnancy is compulsory to detect potential early signs of complications. KEYWORDS: complete hydatidiform mole, gestational trophoblastic disease, twin pregnancy
Minimally-aggressive gestational trophoblastic neoplasms
Gynecol Oncol. 2012 Apr;125(1):145-50. Epub 2011 Dec 22.
Cole LA. Abstract INTRODUCTION: We have previously defined a new syndrome "Minimally-aggressive gestational trophoblastic neoplasms" in which choriocarcinoma or persistent hydatidiform mole has a minimal growth rate and becomes chemorefractory. Previously we described a new treatment protocol, waiting for hCG rise to >3000 mIU/ml and disease becomes more advanced, then using combination chemotherapy. Initially we found this treatment successful in 8 of 8 cases, here we find this protocol appropriate in a further 16 cases. Initially we used hyperglycosylated hCG, a limited availability test, to identify this syndrome. Here we propose also using hCG doubling rate to detect this syndrome. METHODS: Minimally aggressive gestational trophoblastic disease can be detected by chemotherapy resistance or low hyperglycosylated hCG, <40% of total hCG. It can also be identified by hCG doubling rate, with doubling time greater than 2weeks. RESULTS: Nineteen new cases were identified as having minimally aggressive gestational trophoblastic disease by hyperglycosylated hCG and by hCG doubling test. All were recommended to hold off further chemotherapy until hCG >3000mIU/ml. One case died prior to the start of the study, one case withdrew because of a lung nodule and one withdrew refusing the suggested combination chemotherapy. The remaining 16 women were all successfully treated. DISCUSSION: A total of 8 plus 16 or 24 of 24 women were successfully treated using the proposed protocol, holding back on chemotherapy until hCG >3000mIU/ml. Copyright © 2011 Elsevier Inc. All rights reserved.
Chemotherapy and human chorionic gonadotropin concentrations 6 months after uterine evacuation of molar pregnancy: a retrospective cohort study
Lancet. 2012 Jan 14;379(9811):130-5. Epub 2011 Nov 28.
Agarwal R, Teoh S, Short D, Harvey R, Savage PM, Seckl MJ. Source Imperial College London, London, UK. Abstract BACKGROUND: Indications for chemotherapy in gestational trophoblastic disease include raised human chorionic gonadotropin (hCG) concentrations 6 months after uterine evacuation of hydatidiform mole, even when values are falling. We aimed to establish whether chemotherapy is always necessary in these patients. METHODS: We retrospectively identified women registered between January, 1993, and May, 2008, at Charing Cross Hospital, London, UK, who had persistently high hCG concentrations 6 months after evacuation of hydatidiform mole. Rates of hCG normalisation, relapse, and death were assessed in patients continued under surveillance and those who received chemotherapy after 6 months. We postulated that a surveillance policy would be clinically acceptable if hCG values returned to normal in 75% of patients or more. FINDINGS: 76 (<1%) of 13,960 patients with hydatidiform moles had persistently high hCG concentrations of more than 5 IU/L 6 months after evacuation. 66 (87%) patients continued under surveillance and hCG values spontaneously returned to normal without chemotherapy in 65 (98%) of these patients. Values in one patient did not become normal because of chronic renal failure, but she remains healthy. Ten patients received chemotherapy, and hCG concentrations returned to normal in eight (80%) of these individuals (surveillance vs chemotherapy groups p=0·044) and remained slightly high (6-11 IU/L) in two without any associated clinical problems off treatment. We noted no significant differences between individuals in the surveillance and chemotherapy groups, apart from lower median hCG concentrations 6 months after evacuation in those under surveillance than in those given chemotherapy (13 IU/L, range 5-887, vs 157 IU/L, range 6-6438; p=0·004). Overall, there were no deaths in this series. INTERPRETATION: A surveillance policy seems to be clinically acceptable in patients with low and declining concentrations of hCG 6 months after evacuation of hydatidiform mole. FUNDING: National Commissioning Group, Imperial Experimental Cancer Medicine Centre, Imperial Biomedical Research Centre, and Cancer Research UK. Copyright © 2012 Elsevier Ltd. All rights reserved. Comment in Lancet. 2012 Jan 14;379(9811):98-100.
Management of molar pregnancy
J Prenat Med. 2009 Jan;3(1):15-7.
Cavaliere A1, Ermito S, Dinatale A, Pedata R. Author information Abstract Gestational Trophoblastic Disease (GTD) originates from placental tissue and is among the rare human tumors that can be cured even in the presence of widespread metastases. GTD include a spectrum of interrelated tumors including complete and partial hydatidiform mole, invasive mole, choriocarcinoma, and placental site trophoblastic tumor, that have different propensities for local invasion and spread. Although most GTD develop after a mole, they can follow any antecedent pregnancy.Transvaginal ultrasound, routinary dosage of beta-hCG and current approaches to chemotherapy, let most women with malignant gestational trophoblastic disease to be cured and their reproductive function preserved. KEYWORDS: chemotherapy; gestational trophoblastic disease; human chorionic gonadotropin PMID: 22439034 PMCID: PMC3279094