Gestational Trophoblastic Tumor
Gestational trophoblastic tumours (GTT) are a rare group of diseases in which the tissues formed in the uterus following conception grow abnormally to form a tumour. Most GTTs are benign (not cancer) and do not spread, but some types can become malignant (cancer) and spread to nearby tissues or distant parts of the body. There are three main types of gestational trophoblastic tumours: (i) hydatidiform mole (aslo known as molar pregnancy) - this is where the sperm and egg have joined but the tissues formed develop into a cyst; and (ii) choriocarcinoma - this can begin from a hydatidiform mole or from tissue that remains in the uterus following the delivery of a baby; (iii) placental-site trophoblastic disease - this is very rare and starts in the area of the uterus where the placenta was attached.
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MeSH term: Gestational Trophoblastic Disease
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Allelic Characterization of IGF2 and H19 Gene Polymorphisms in Molar Tissues.
Asian Pac J Cancer Prev. 2016; 17(9):4405-4408 [PubMed] Related Publications
MATERIALS AND METHODS: Forty-nine specimens of molar tissues as well as 100 control normal placental tissues, delivered on the same days, were collected. Polymerase chain reaction (PCR) with restriction fragment length polymorphism (RFLP) on 2% agarose gel electrophoresis was conducted to determine the allelic distribution. The ApaI polymorphism within exon 9 of IGF2 and the RsaI polymorphism within exon 5 of H19 were employed to identify the allelic distribution of the IGF2 and H19 genes, respectively. Then the data for these genes in the molar and normal placenta tissues were compared.
RESULTS: The allelic distribution of IGF2 genes found in molar tissue were 21 (42.9%) aa (undigested), 10 (20.4%) ab (heterozygous) and 18 (36.7%) bb (digested), while in normal placenta tissue the values were 22 (22%) aa, 51 (51%) ab, and 27 (27%) bb. The allelic distribution of H19 in molar tissues was 8 (16.2%) aa (undigested), 8 (16.3%) ab (heterozygous) and 33 (67.4%) bb (digested) and in normal placental tissue was 16 (16%) aa, 36 (36%) ab and 48 (48%) bb in normal placenta tissue. These results were significantly different with P values of 0.001 and 0.037 for the allelic distribution of IGF2 and H19, respectively.
CONCLUSIONS: Molar tissues showed significant differences of allelic distribution of IGF2 and H19 from normal placenta tissues.
Treatment Outcomes of Gestational Trophoblastic Neoplasia in King Chulalongkorn Memorial Hospital over Two Decades.
J Reprod Med. 2016 May-Jun; 61(5-6):238-42 [PubMed] Related Publications
STUDY DESIGN: This retrospective study recruited all GTN patients who were treated at King Chulalongkorn Memorial Hospital during the period January 1994-December 2013. Clinical data were collected. Statistical analyses were performed, with p values < 0.05 considered statistically significant.
RESULTS: There were 183 GTN cases during the study period, resulting in an incidence of 1.03 cases per 1,000 deliveries. Fifty-five cases (30.1%) were diagnosed as GTN following nonmolar pregnancy, and 128 cases were identified as postmolar GTN. A total of 113 cases were diagnosed as stage I, 12 as stage II, 40 as stage III, and 17 as stage IV; 125 cases (68.3%) were clas- sified as low risk, and 57 cases (31.1%) as high risk. Actinomycin D was the most frequently used first-line single-agent chemotherapy (98 cases), and VAC regimen was the most frequently used combination chemotherapy (24 cases). EMACO regimen was the most frequently used second-line chemotherapy (11 cases). The median number of chemotherapy courses was 4.5 courses in the first decade and 6 courses in the second decade of our study (p = 0.005). Median duration of treatment was 72 days (range, 7-491 days). Overall remission rate was 82.6%, with rates of 76% in the first decade and 90.8% in the second decade of the study (p=0.03).
CONCLUSION: Incidence of high-risk GTN increased over the course of the study period at our national referral hospital. Improvement in patient outcomes was observed, being directly associated with improved targeted chemotherapy regimens.
Evolution of a Teenage and Young Adult Service, in Sheffield, U.K., for Patients with Gestational Trophoblastic Neoplasia.
J Reprod Med. 2016 May-Jun; 61(5-6):235-7 [PubMed] Related Publications
BACKGROUND: Since its opening in 2002 the TYA unit has demonstrated its effectiveness and ability to care for GTN patients, offering additional emotional assessment and meeting the specific needs that many young GTN patients have. Patients using the TYA unit were identified from the Centre's databases, and individual records were scrutinized for demographics, clinical presentation, barriers to care, compliance, and specific needs.
RESULTS: Of the 121 GTN patients who have utilized the facilities, there were 94 complete moles, 11 choriocarcinomas, 3 placental site trophoblastic tumors, 1 twin molar pregnancy, and 4 with persistent unexplained hCG elevation. Presenting with a complicated social background was identified as a barrier to care in 8 patients. In addition to patients, 40 relatives and 12 infants have also utilized the facilities. A total of 33% of patients and carers had social work input and/or refer-ral to psychology services.
CONCLUSION: The bespoke service and care offered to TYA patients is appropriate and should be considered the gold standard for young patients, enabling them to cope with their unique challenges during diagnosis and treatment.
Comparison of Cost-Effectiveness Between Actinomycin D Versus Methotrexate-Folinic Acid in the Treatment of Low-Risk Gestational Trophoblastic Neoplasia.
J Reprod Med. 2016 May-Jun; 61(5-6):230-4 [PubMed] Related Publications
STUDY DESIGN: A comparative cost-effectiveness analysis was performed from a societal perspective. A decision tree model was developed comparing 2 alternative treatment options: initial 5-day Act-D and 8-day MTX-FA. Treatment would be switched to another regimen in case of resistance. The outcome of interest is number of days to remission. Clinical data was obtained from our previous study in which Act-D demonstrated 100% remission rates as compared to 73.6% for MTX-FA. Cost of treatment data, which includes chemotherapeutics, accessory medications, laboratory tests, and hospital fees, was obtained from a university hospital. Patient-related travel cost and opportunity cost due to absence from work were also included. All costs were calculated to 2015 base year.
RESULT: Costs per treatment cycle were $308.01 and $227.20 US dollars (USD) for 5-day Act-D and 8-day MTX-FA, respectively. Expected time toward treatment completion for Act-D was 12.6 days shorter than for MTX-FA. Expected costs toward remission for initial treatment with Act-D and MTX-FA were $1,078.04 and $1,064.56 USD, respectively, i.e., an incremental cost effectiveness ratio (ICER) of $1.07 USD/day of earlier treatment completion. After sensitivity analysis, remission rate of lower than 72% would make initial treatment with MTX-FA more expensive than with Act-D.
CONCLUSION: Treatment costs of low-risk GTN are almost equal between the 2 treatment options with different time to remission. Initial treatment with MTX-FA is slightly less expensive, but there is longer time to remission. The ICER of initial treatment with Act-D over MTX-FA is $1.07 USD/day of earlier treatment completion.
Centralized Coordination of Decentralized Assistance for Patients with Gestational Trophoblastic Disease in Brazil: A Viable Strategy for Developing Countries.
J Reprod Med. 2016 May-Jun; 61(5-6):224-9 [PubMed] Related Publications
STUDY DESIGN: We developed a questionnaire composed of 15 questions, which was sent by email to the 38 Brazilian GTD Reference Center (BGTDRC) Directors who are members of the Brazilian Association of GTD, in order to characterize the professionals involved in the care of patients with GTD and the type of assistance provided.
RESULTS: The Directors of the BGTDRCs are usually specialists in Gynecology and Obstetrics (97%), with a median experience of a decade in treating women with GTD. The BGTDRCs are linked to university hospitals in 75% of centers and provide completely free medical care in 87%. However, 52% of centers do not perform chemotherapy in their reference center, and patients are referred elsewhere for chemotherapy. Despite some difficulties, the rate of patients lost to follow-up before human chorionic gonadotropin remission is 9%, and the GTD mortality rate is 0.9%.
CONCLUSION: Due to large regional disparities, the BGTDRCs are not uniformly organized. However, under the coordination of the Brazilian Association of GTD there is now strong communication and collaboration among reference centers, which has significantly advanced both patient care and research into the management of these diseases.
Comparison Between Pathological Diagnosis and Cytogenetic Diagnosis by Short Tandem Repeat Polymorphism Analysis of Suspected Molar Pregnancies.
J Reprod Med. 2016 May-Jun; 61(5-6):219-23 [PubMed] Related Publications
STUDY DESIGN: Patients were recruited for the molecular diagnostic study of suspected molar pregnancy at Chiba University Hospital between 2007 and 2011. Gynecologists performed macroscopic diagnoses immediately after the evacuation. Pathological diagnoses were then made by pathologists in routine bases without performing p57Kip2 immunostaining. Molecular cytogenetic diagnosis was performed via short tandem repeat (STR) polymorphism analysis. Androgenetic, biparental triploid, and biparental diploid villous tissues determined on STR polymorphism analysis were classified as complete hydatidiform mole (CHM), partial hydatidiform mole (PHM), and abortion, respectively.
RESULTS: A total of 86 patients were enrolled. The number of CHMs, PHMs, and abortions on cytogenetic diagnoses were 64, 9, and 13, respectively. The concordance rate between macroscopic and cytogenetic diagnoses was 85% (CHM: 56, PHM: 4, and abortions: 13). The concordance rate between histopathological and cytogenetic diagnoses was 87% (CHM: 59, PHM: 5, and abortions: 10). The complete agreement rate among the 3 categories was 78% (CHM: 55, PHM: 3, and abortions: 10).
CONCLUSION: Neither macroscopic nor histopathological diagnoses were perfect, but both were quite accurate in a single trophoblastic center.
Maternal Near Miss According to World Health Organization Classification Among Women with a Hydatidiform Mole: Experience at the New England Trophoblastic Disease Center, 1994-2013.
J Reprod Med. 2016 May-Jun; 61(5-6):210-4 [PubMed] Related Publications
STUDY DESIGN: This study included patients with molar pregnancy at the NETDC between 1994 and 2013. Clinical and pathologic reports were reviewed. PLTC and MNM criteria and maternal deaths were searched in medical records using the World Health Organization criteria and classification.
RESULTS: We identified 375 patients with molar pregnancy and no patient developed a MNM or maternal death. Only 6 (1.6%) had PLTCs (hemorrhage with hemodynamic instability, severe preeclampsia, respiratory distress, blood transfusion, and ICU admission).
CONCLUSION: We observed a low rate of PLTC and no cases of MNMs or maternal deaths related to molar pregnancy, likely due to earlier diagnosis at the NETDC in recent years.
Anti-Müllerian Hormone in Patients Treated with Chemotherapy for Gestational Trophoblastic Neoplasia Does Not Predict Short-Term Fertility.
J Reprod Med. 2016 May-Jun; 61(5-6):205-9 [PubMed] Related Publications
STUDY DESIGN: The GTN database of our national referral center was screened from 2008-2012 for patients undergoing AMH testing, and subsequent fertility outcomes were reviewed.
RESULTS: Of 470 treated patients, 3 underwent AMH testing for evaluation of potential subfertility 4-13 months following multiagent chemotherapy, with levels rangingfrom 0.07-4.62 pmol/L. All 3 were counseled by independent fertility specialists of the low probability of subsequent conception but went on to initiate spontaneously conceived pregnancies within 2-9 months, resulting in healthy infants.
CONCLUSION: Low serum AMH is not a reliable predictor of reduced short-term fertility postchemotherapy for GTN and should be interpreted with caution when counseling patients in this setting.
The Role of Surgery in the Management of Gestational Trophoblastic Neoplasia The Hungarian Experience.
J Reprod Med. 2016 May-Jun; 61(5-6):197-204 [PubMed] Related Publications
STUDY DESIGN: Between January 1, 1977, and December 31, 2014, 371 patients with low-risk GTN and 190 patients with high-risk GTN were treated with chemotherapy, surgical interventions, or both. The indications for hysterectomy included excision of large uterine tumor masses, uterine hemorrhage or sepsis, or a drug-resistant uterine focus. Metastases were excised due to the presence of drug-resistant foci or complications of disease such as hemorrhage.
RESULTS: Over the period of 1977-2014 74 hysterectomies, 15 resections of vaginal metastases, 3 omentectomies, 13 adnexectomies, 9 lung resections, I nephrectomy, 1 lung resection and nephrectomy, and 2 craniotomies were performed among our patients. While hysterectomy was performed in 51 (26.8%) of 190 high-risk patients, hysterectomy was performed in only 23 (6.2%) of 371 low-risk patients (p < 0.01). From 1977-2006 metastases were resected in 18.3% (26/142) and from 2007-2014 in 16.7% (8/48) of high-risk patients.
CONCLUSION: In our center surgery, particularly in the form of hysterectomy, still plays a valuable role in the management of both low- and high-risk GTN.
Follow-Up After Molar Pregnancy Evacuation: Feasibility of Using Semi-Quantitative Urine Pregnancy Tests.
J Reprod Med. 2016 May-Jun; 61(5-6):192-6 [PubMed] Related Publications
STUDY DESIGN: A retrospective review of complete hydatidiform moles at a safety-net hospital from 2003-2013 was performed. hCG curves were used to extrapolate expected SQPT results over timefor a resolving hydatidiform mole.
RESULTS: Of 61 complete moles, 37 had an uncomplicated hCG decline and at least 4 serum hCG results. All of those patients had hCG < 10,000 mIU/mL within 15 days, < 2,000 within 64 days, < 500 within 70 days (92.2% within 1 month), < 100 within 89 days (90% within 2 months), and < 25 within 152 days (95.2% within 3 months). After reaching levels < 25, hCG rose only in cases of new pregnancies.
CONCLUSION: Based on this retrospective analysis, SQPT monitoring could have avoided 90% of blood draws while still flagging all patients with subsequent postmolar GTN within 45 days by limiting blood draws to (1) patients with SQPT levels of > 10,000, > 500, and >100 mIU/mL at 15, 30, and 45 days, respectively, (2) hCG > 25 after 60 days, or (3) increasing SQPT levels.
Timing of Referral to the New England Trophoblastic Disease Center: Does Referral with Molar Pregnancy Versus Postmolar Gestational Trophoblastic Neoplasia Affect Outcomes?
J Reprod Med. 2016 May-Jun; 61(5-6):187-91 [PubMed] Related Publications
STUDY DESIGN: The records of the New England Trophoblastic Disease Center (NETDC) were queried for all patients with molar pregnancy or PMGTN from 1993-2013. Retrospective chart review was performed to extract relevant clinical and demographic data. Parametric and nonparametric tests were utilized to compare variables.
RESULTS: From 1993-2013, 429 women with molar disease were evaluated at the NETDC. Of those, 68% were referred with molar pregnancy and 32% were referred with PMGTN. Comparing women with PMGTN who were referred with a molar pregnancy versus referred with PMGTN, the women were of equivalent stage and World Health Organization (WHO) score. Additionally, referral with molar pregnancy or PMGTN did not associate with time to persistence, time to remission, or number of lines of chemotherapy administered.
CONCLUSION: In this trophoblastic disease specialty center in the United States, referral at the time of PMGTN as opposed to at diagnosis of molar pregnancy did not appear to affect the stage or WHO score at diagnosis, the need for multiple chemotherapy lines, or time to remission.
Utilization of Chromogenic In Situ Hybridization to Assess Ploidy in the Diagnosis of Hydatidiform Mole.
Am J Clin Pathol. 2016; 146(1):125-31 [PubMed] Related Publications
METHODS: CISH using probes to chromosomes 17 and 10 was performed on 20 POC cases with known cytogenetics to establish a reference percentage. This was then used to classify a randomized set of abnormal and normal cases.
RESULTS: An abnormal CISH cutoff of greater than 7% was established. All abnormal cases (six triploid and three tetraploid), 11 "normal" (46, XX or XY or undetectable abnormalities), and one trisomy 10 were all correctly classified by the assay.
CONCLUSIONS: CISH is a useful ancillary technique for the diagnosis of molar pregnancy. Its greater accessibility and ability to score even rare placental tissue in a background of maternal tissue offer advantages over other methods.
Immunohistochemical Expression and Clinical Significance of Wnt11 and BCL2A1 in Complete Moles.
Anal Quant Cytopathol Histpathol. 2016; 38(2):79-86 [PubMed] Related Publications
STUDY DESIGN: The expression of Wnt11 and BCL2A1 in 84 complete moles and 30 normal first-trimester villi were detected by Envision immunohistochemistry. Quantitative evaluation according to color deconvolution and immunoreactive score was performed. Data was analyzed using Kruskal-Wallis test, Pearson test, and ROC curve.
RESULTS: Of 84 complete moles, 14 developed to post-molar gestational trophoblastic neoplasia, and the others regressed spontaneously. Both proteins showed cytoplasmic pattern, whereas the DAB wt% of BCL2A1 and Wnt11 expression was highest in moles that developed to GTN, gradually reduced in spontaneously regressed moles and normal villi (all p < 0.01). We considered a 23.17% cutoff valuefor Wnt11 DAB wt% and 16.31% for BCL2A1 DAB wt% to assess molar progression to GTN. There was positive correlation between expressions of the 2 proteins (r = 0.403).
CONCLUSION: Our findings demonstrated immunohistochemical expression of Wnt11 and BCL2A1 in complete moles and normal villi. Both proteins may be included as part of an immunohistochemical panel to identify postmolar outcome when other trophoblastic markers yield ambiguous results.
Prognosis of Patients with Gestational Trophoblastic Neoplasia and Obstetric Outcomes of Those Conceiving After Chemotherapy.
Anticancer Res. 2016; 36(7):3477-82 [PubMed] Related Publications
PATIENTS AND METHODS: Sixty-six patients had diagnosis of hydatiform mole on curettage and 18 developed GTN. Two patients were referred with pathological diagnosis of GTN. Chemotherapy was tailored according to International Federation of Gynecology and Obstetrics risk scoring system.
RESULTS: All patients with GTN but one, were recovered by chemotherapy and had no evidence of disease after a median follow-up of 80 months. Only the patient with epithelioid trophoblastic tumor died of disease. Seven out of the eight women who tried to conceive after chemotherapy became pregnant. Ten conceptions occurred, resulting in no molar pregnancy, three miscarriages and seven term-live healthy births (70.0%). All seven babies showed normal development and growth after a median follow-up of 38 months.
CONCLUSION: The prognosis of women with GTN is very good, and obstetric outcomes of those who conceive after chemotherapy are similar to those of the general population.
Spontaneous renal hemorrhage caused by invasive mole: a case report.
Eur J Gynaecol Oncol. 2016; 37(3):417-9 [PubMed] Related Publications
CONCLUSION: Post-operational pathological examination revealed trophoblasts within the lesions present in uterine fundus and the residue images of a few trophoblasts present in the left renal mass.
Diginyc partial hydatidiform mole with increased fetal nuchal translucency and ovarian hyperstimulation syndrome.
Clin Exp Obstet Gynecol. 2016; 43(3):467-9 [PubMed] Related Publications
CASE REPORT: A case of diginyc partial HM at 12 weeks of gestational age was referred to the present center of prenatal diagnosis. The patient showed ovarian hyperstimulation syndrome. At ultrasonography, increased fetal nuchal translucency (NT) with fetal anomaly was evident, without sonographic signs of placental mole. Pregnancy was terminated with legal abortion.
RESULTS: Partial HM (PHM) was suspected by ultrasonographic fetal markers with ovarian hyperstimulation syndrome, but the diagnosis was performed only with fluorescent in situ hybridization. In particular fetal NT appeared increased also in diginyc mole.
CONCLUSION: In order to improve the detection rate of PHM, routine histological examinations may be associated to fluorescent in situ hybridization in all cases of fetal anomalies.
Evaluation of sialic acid levels in patients with hydatidiform mole: a preliminary study.
Clin Exp Obstet Gynecol. 2016; 43(3):414-6 [PubMed] Related Publications
MATERIALS AND METHODS: A total of 114 women were enrolled in this study. Patients were divided into three groups including HM (Group 1, n = 34), control group including non-pregnant healthy patients (Group 2, n = 42), and another control group including healthy pregnant patients within 12 weeks of gestation (Group 3, n = 38). Serum-free SA levels were measured.
RESULTS: There was a statistically significant difference in serum-free SA levels among the groups (p ≤ 0.001). Patients with HM had significantly higher levels compared to the control groups.
CONCLUSION: The present study results showed that there was a significant correlation between HM and serum SA level.
First-line chemotherapy in low-risk gestational trophoblastic neoplasia.
Cochrane Database Syst Rev. 2016; (6):CD007102 [PubMed] Related Publications
OBJECTIVES: To determine the efficacy and safety of first-line chemotherapy in the treatment of low-risk GTN.
SEARCH METHODS: We electronically searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase in September 2008, February 2012, and January 2016. In addition, we searched online trial registers for protocols and ongoing trials.
SELECTION CRITERIA: For the original review, we included randomised controlled trials (RCTs), quasi-RCTs and non-RCTs that compared first-line chemotherapy for the treatment of low-risk GTN. For this updated versions of the review, we included only RCTs.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion and extracted data to a pre-designed data extraction form. Meta-analysis was performed using the random-effects model.
MAIN RESULTS: We included seven RCTs (667 women) in this updated review. Most studies were at a low or moderate risk of bias and all compared methotrexate with actinomycin D. Three studies compared weekly intramuscular (IM) methotrexate with bi-weekly pulsed intravenous (IV) actinomycin D (393 women), one study compared five-day IM methotrexate with bi-weekly pulsed IV actinomycin D (75 women), one study compared eight-day IM methotrexate-folinic acid (MTX-FA) with five-day IV actinomycin D (49 women), and one study compared eight-day IM MTX-FA with bi-weekly pulsed IV actinomycin D. One study contributed no data. Moderate-certainty evidence indicates that actinomycin D is probably more likely to lead to primary cure than methotrexate (risk ratio (RR) 0.65, 95% confidence interval (CI) 0.57 to 0.75; six trials, 577 participants; I(2) = 26%), and first-line methotrexate treatment is probably more likely to fail than actinomycin D treatment (RR 3.55, 95% CI 1.81 to 6.95; six trials, 577 participants; I(2) = 61%; moderate-certainty evidence) Low-certainty evidence suggests that there may be little or no difference between methotrexate and actinomycin D treatment with respect to nausea (four studies, 466 women; RR 0.61, 95% CI 0.29 to 1.26) or any of the other individual side-effects reported, although data for all of these outcomes were insufficient and too inconsistent to be conclusive. Low-certainty evidence suggests that there may be little or no difference in the risk of severe adverse events (SAEs) between the groups overall (five studies, 515 women; RR 0.35, 95% CI 0.08 to 1.66; I² = 60%); however, the direction of effect favours methotrexate and more evidence is needed. Furthermore, evidence from subgroup analyses suggests that actinomycin D may be associated with a greater risk of SAEs than methotrexate (low-certainty evidence). We found no evidence on the effect of these treatments on future fertility.
AUTHORS' CONCLUSIONS: Actinomycin D is probably more likely to achieve a primary cure in women with low-risk GTN, and less likely to result in treatment failure, than a methotrexate regimen. There may be little or no difference between the pulsed actinomycin D regimen and the methotrexate regimen with regard to side-effects. However, actinomycin D may be associated with a greater risk of severe adverse events (SAEs) than a methotrexate regimen. Higher-certainty evidence is still needed on treating low-risk GTN and the four ongoing trials are likely to make a significant contribution to this field. Given the variety of treatment regimens, findings from these trials could facilitate a network meta-analysis in the next version of this review to help women and clinicians determine the best treatment options for low-risk GTN.
A 10-Year Clinical Experience of Gestational Trophoblastic Disease at Rajavithi Hospital, 2001-2010.
J Med Assoc Thai. 2016; 99 Suppl 2:S17-27 [PubMed] Related Publications
OBJECTIVE: To analyze the clinical characteristics, incidence and treatment outcomes of GTD at Rajavithi Hospital.
MATERIAL AND METHOD: Medical records of women diagnosed with GTD at Rajavithi Hospital from January 1, 2001 to December 31, 2010 were retrospectively reviewed. Disease diagnosis, treatment and follow-up data were analyzed.
RESULTS: A total of 329 cases of GTD were reviewed. HM was diagnosed in 167 patients (incidence 2.32 per 1,000 deliveries); 26 patients were lost to follow-up; and 49 of the remaining 141 patients (34.8%) developed post-molar GTN. In multivariable analysis, uterus >16 week size and pre-treatment human chorionic gonadotropin (hCG) level >250,000 mIU/mL were the significant risk factors for developing post-molar GTN. Of 162 patients with GTN (incidence 2.25 per 1,000 deliveries), 15 patients were lost to follow-up, and 116 patients, 29 patients and 2 patients were classified as having low-risk GTN, high-risk GTN and placental site trophoblastic disease respectively. The overall survival rate in the low-risk group was 100% whereas in the high-risk group it was 86.2%. A modified WHO prognostic score of more than five was the significant risk factor for developing resistant GTN.
CONCLUSION: GTD treatment at Rajavithi Hospital showed excellent clinical outcomes. Uterus >16 weeks size and pre- treatment hCG > 250,000 mIU/mL were the significant risk factors for developing post-molar GTN in HM patients. Classifying GTN patients into low- and high-risk groups was useful in planning treatment and counseling.
E-Cadherin, CD44v6, and Insulin-Like Growth Factor-II mRNA-Binding Protein 3 Expressions in Different Stages of Hydatidiform Moles.
J Biochem Mol Toxicol. 2016; 30(9):455-61 [PubMed] Related Publications
Role of P57KIP2 Immunohistochemical Expression in Histological Diagnosis of Hydatidiform Moles.
Asian Pac J Cancer Prev. 2016; 17(4):2061-6 [PubMed] Related Publications
MATERIALS AND METHODS: Hydatidiform mole patients at King Chulalongkorn Memorial Hospital between January 1999 and December 2011 were recruited. Two gynecologic pathologists reviewed histopathologic slides to confirm diagnosis. Formalin-fixed, paraffin-embedded tissue sections were stained using a bstandard immunostaining system with monoclonal antibodies against P57KIP2 protein. Correlations among pathological features, immunohistochemical expression and clinical data were analyzed.
RESULTS: One hundred and twenty-seven hydatidiform mole patients were enrolled. After consensus review, 97 cases were diagnosed as complet (CHM) and 30 cases as partial (PHM). Discordance between the first and final H and E diagnoses was found in 19 cases (14.9%, k= 0.578). Significant pathological features to classify the type of hydatidiform mole are central cisterns, trophoblastic proliferation, trophoblastic atypia, two populations of villi, fetal vessels and scalloped borders. After performing immunohistochemistry for P57KIP2, 107 cases were P57KIP2 negative and 20 cases positive. Discordant diagnoses between final H and E diagnosis and P57KIP2 immunohistochemistry was identified in 12 cases (9.4%). Sensitivity of final H and E diagnosis for CHM was 89.7%; specificity was 95.0%. PHM sensitivity and specificity of final H and E diagnosis was 95.0% and 89.7%, respectively.
CONCLUSIONS: Histopathological diagnosis alone has certain limitations in accurately defining types of hydatidiform mole; P57KIP2 immunohistochemistry is practical and can be a useful adjunct to histopathology to distinguish CHM from non-CHM.
Gestational trophoblastic disease in a Greenlandic Inuit: diagnosis and treatment in a remote area.
BMJ Case Rep. 2016; 2016 [PubMed] Related Publications
Mental Representations of Illness in Patients with Gestational Trophoblastic Disease: How Do Patients Perceive Their Condition?
PLoS One. 2016; 11(4):e0153869 [PubMed] Free Access to Full Article Related Publications
METHODS: Thirty-one women diagnosed with Gestational Trophoblastic Disease in a hospital in Italy were asked to complete the Illness Perception Questionnaire-Revised to measure the following: illness Identity, illness opinions and causes of Gestational Trophoblastic Disease.
RESULTS: High mean scores were observed in the Emotional representations and Treatment control subscales. A significant difference emerged between hydatidiform mole patients and those with gestational trophoblastic neoplasia on the Identity subscale. A significant correlation emerged between "time since diagnosis" and the Treatment control subscale.
DISCUSSION: This study is the first to investigate illness perception in Gestational Trophoblastic Disease. From a clinical perspective the results highlight the need for multidisciplinary support programs to promote a more realistic illness perception.
Conservative Chemotherapy in Gestational Trophoblastic Disease: Experience With Etoposide, Methotrexate, and Dactinomycin Chemotherapy.
Int J Gynecol Cancer. 2016; 26(4):790-5 [PubMed] Related Publications
METHODS: The medical records of 58 patients who received EMA chemotherapy in groups A, B, and C in the 2000 to 2012 period at St Mary's Hospital were examined. Clinical characteristics, chemotherapy responses, causes of treatment failure, and cases of drug toxicity were analyzed retrospectively.
RESULTS: Treatment with the EMA regimen resulted in primary remission in 52 (96%) of 54 patients and resistance in 2 of the patients (3%). In the resistance group, one belonged to group B and was treated with etoposide, MTX, and actinomycin D with cyclophosphamide and vincristine (EMA-EP) and the other belonged to group A and died of refractory disease. World Health Organization (WHO) grade 4 leukocytopenia and thrombocytopenia with the EMA regimen occurred in 6% and 0.4% of the cycles, respectively; the other toxic effects were acceptable and manageable. Median cycles of EMA chemotherapy during the treatment were 7, 8, and 8 in groups A, B, and C, respectively. There was some reduction in total chemo cycle and toxicity, as compared with a previously reported study using the alternative cyclophosphamide and vincristine regimen. Among the EMA treated patients, 1 patient with a second malignancy of breast cancer was documented. In addition, 5 child births for the treated patients were recorded during the follow-up period of mostly 10 years.
CONCLUSIONS: The EMA chemotherapy seemed to reduce treatment duration and the relapse rate without increasing the adverse effects in patients with MTX resistance and low-risk GTD, but having confirmed metastatic lesions. Although this study had some limitations regarding the high-risk GTD, our findings will provide a basis for the use of EMA chemotherapy when cyclophosphamide and vincristine is contraindicated due to toxicity.
Outcomes of Metastatic Gestational Trophoblastic Neoplasia: Fourteen Year Experience from a Northern Thailand Tertiary Care Center.
Asian Pac J Cancer Prev. 2016; 17(3):1357-62 [PubMed] Related Publications
Recurrent vomiting in a woman due to miscarriage: think out of the box.
BMJ Case Rep. 2016; 2016 [PubMed] Related Publications
Management of gestational trophoblastic disease: a survey of New Zealand O&G practice.
N Z Med J. 2016; 129(1431):38-45 [PubMed] Related Publications
METHOD: An electronic survey approved by the RANZCOG Continues Professional Development Committee was distributed amongst registered O&G Specialists currently working in New Zealand. Data were analysed using Microsoft Excel 2011. Frequency distributions were used to determine the percentage of participants responding to the listed alternatives for each question.
RESULTS: There were 234 potential responders, but only 68 complete questionnaires were received and available for analysis. The diagnosis of GTD requires histopathological analysis of pregnancy tissue, however only 79.7% of participants request this test routinely. Sixty-five percent of Fellows thought that a number of molar pregnancies can be missed with increasing proportion of medically-managed miscarriages, reliance on ultrasound and appearance of the tissue being contributing factors. Sixty-six percent of specialists were directly involved in the management of patients with GTD to various degrees. Follow-up responsibilities were divided between designated O&G specialists (52.3%), specialised gynaecology clinics (29.2%), acute assessment units (13.8%), nurse specialists (12%), O&G registrars (10.8%), GPs (6.2%), and others (6.2%). NZGCG guidelines were used by the majority of responders (54.8%), followed by local (29%) and RCOG (27.4%) guidelines. Seventy-two percent of specialists felt that some form of centralisation in the management of GTD is needed.
CONCLUSION: In spite of the low response rate, our research demonstrates existing practice heterogeneity at every level of care. It also confirms that there is a desire for some form of centralisation in diagnosis and management of GTD, and a definite need for data collection in the form of a national register.
False Negative Urine Pregnancy Testing with Complete Molar Pregnancy: An Example of the Hook Effect.
S D Med. 2016; 69(2):55-7 [PubMed] Related Publications
CASE PRESENTATION: A 49-year-old Caucasian female with past medical history pertinent for deep vein thrombosis, ovarian cysts, and osteopenia presented to her internist with report of irregular uterine bleeding for the preceding three months, accompanied by complaints of abdominal bloating, night sweats, and constipation. The patient stated she had completed two negative qualitative urine pregnancy tests and had been seen by both gynecology and gastroenterology, with recommendations to start supplemental estrogen for her symptoms and begin additional fiber intake for irritable bowel syndrome, respectively. Despite negative urine beta-hCG, a quantitative serum beta-hCG was obtained and revealed a level greater than 200,000 international units (IU). The patient was referred to gynecologic oncology and an open abdominal hysterectomy with preservation of her ovaries was performed. Histopathologic examination showed a complete hydatiform mole with no evidence of invasion.
CONCLUSION: The case highlights the importance of clinical judgment in modern medicine, where biochemical methods and imaging modalities have become main stays in diagnosis. As mentioned, there are ways to reduce the incidence of the hook effect, but with added time and cost. Clinicians need to consider the possibility of the hook effect for instances where the clinical picture points to a disease entity despite negative test results. Delaying diagnoses, as illustrated with GTD, has the potential to cause significant morbidity and mortality.
Expression patterns of ERVWE1/Syncytin-1 and other placentally expressed human endogenous retroviruses along the malignant transformation process of hydatidiform moles.
Placenta. 2016; 39:116-24 [PubMed] Related Publications
METHODS: Syncytin-1 glycoprotein was localized by immunohistochemistry in hydatidiform moles, gestational trophoblastic neoplasia and control placentas. The transcription levels of its locus ERVWE1, its interaction partners (hASCT1, hASCT2, TLR4 and DC-SIGN) and two loci (ERVFRDE1 and ERV3) involved the expression of other placental envelopes were assessed by real-time PCR.
RESULTS: Syncytin-1 glycoprotein was expressed in syncytiotrophoblast of hydatidiform moles with an apical enhancement when compared with normal placentas. Moles with further malignant transformation had a higher staining intensity of Syncytin-1 surface unit C-terminus but the transcription level of its locus ERVWE1 was not different from that of moles with further remission and normal placentas. hASCT1 and TLR4, showed lower transcription levels in complete moles when compared to normal placentas. ERVWE1, ERVFRDE1 and ERV3 transcription was down-regulated in hydatidiform moles and gestational trophoblastic neoplasia.
CONCLUSIONS: Variations of Syncytin-1 protein localization and down-regulation of hASCT1 and TLR4 transcription are likely to reflect altered functions of Syncytin-1 in the premalignant context of complete moles. The reduced transcription in gestational trophoblastic diseases of ERVWE1, ERVFRDE1 and ERV3, which expression during normal pregnancy is differentially regulated by promoter region methylation, suggest a joint dysregulation mechanism in malignant context.
Circulating Cell Free DNA in the Diagnosis of Trophoblastic Tumors.
EBioMedicine. 2016; 4:146-52 [PubMed] Free Access to Full Article Related Publications