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Objective: To determine the predictive value of plasma soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF) ratio for detection of preeclampsia in elderly gravida at 16–18...

Background: Gestational trophoblastic neoplasia (GTN) can derive either from molar or non-molar pregnancy. Our primary objective is to compare clinical presentation and outcome of treatment of non-molar and post-molar GTN. Our secondary outcome is to evaluate and compare the prognostic factors of non-molar GTN compare to post-molar GTN in subgroup classification of GTN patients by stage and by low-risk and high-risk groups.Methods: Retrospective chart review of GTN patients treated from 2007 to 2016 was done. General characteristics, clinical data, treatment options and treatment outcomes were collected. The cases with missing significant data were excluded. Statistics analysis of the data was performed with SPSS version 22.0. Mean, mode, median and percent were used to present the data. Student t-test, Mann Whitney-U test and Kaplan Meier were used to analyze the data. The results were presented in Tables or graphs where appropriate. Results: Total of 71 GTN patients were recruited into the study. Fifty-one patients were post-molar GTN and 20 were non-molar GTN patients. The mean age of the patients was not different (p=0.25). Median duration from previous pregnancy and time to achieve remission were longer in non-molar GTN (292 days vs. 42 days and 163 vs. 64 days, respectively). Mortality rate of the non-molar GTN is higher that of the post-molar GTN (15% vs. 1.9%). Comparison of stage to stage showed no differences between the post-molar and the non-molar GTN. According to previous pregnancy type, post-abortion had higher resistant to treatment rate than post-term delivery.Conclusion: Non-molar GTN is different form post-molar GTN in several aspects, such as the duration from previous pregnancy, stage and score at diagnosis, treatment resistance and mortality rate. Comparison between the non-molar and post-molar GTN stage by stage and risk scores could not identify the difference between the two groups.

Introduction Protein expression in cells are associated with oncogenesis. This study aims to explore proteomic profiles and discover potential biomarkers that can predict malignant transformation of hydatidiform mole. Methods Retrospective analysis was done in 14 cases of remission hydatidiform mole and 14 cases of hydatidiform mole who later developed malignancy (GTN group). Molar tissues were retrieved from −70 °C frozen tissue. Subsequently, a large-scale proteomic analysis was performed to identify proteins and compare their abundance levels in the preserved molar tissues from these two groups using a dimethyl-labeling technique coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results A total of 2,153 proteins were identified from all samples. 22 and 10 proteins were significantly up-regulated and down-regulated, respectively, in the GTN group compared with the mole group. These altered proteins were found in several biological groups such as cell-cell adhesion, secreted proteins, and ribonucleoproteins. Several hormone-related proteins were among the most up-regulated proteins in the GTN group including choriogonadotropin subunit beta (β-hCG) and alpha (α-hCG), growth/differentiation factor 15, as well as both pregnancy-specific beta-1-glycoproteins 2 and 3. In contrast, protein S100-A11 and l -lactate dehydrogenase A chain, were down-regulated in molar tissue from most patients in the GTN group. Discussion This study identified a set of differentially expressed proteins in molar tissues that could potentially be further examined as predictive biomarkers for the malignant transformation of CHMs. A molar proteome database was constructed and can be accessible online at http://sysbio.chula.ac.th/Database/GTD_DB/Supplementary_Data.xlsx .

to evaluate the role of microsatellite genotyping in discordant results between morphologic examination and p57127 cases of hydatidiform mole who had morphologic examination and p57All controlled cases were confirmed PHM. Two cases of histologic CHM with positive p57Microsatellite genotyping is a high accuracy method for differential diagnosis from complete and partial hydatidiform moles. However, cost of microsatellite genotyping is still too high to use routinely. Therefore, selected use in discrepancy cases may be suitable.

Purpose To determine the significance of P57KIP2 immunohistochemistry expression in the histopathological diagnosis of hydatidiform mole. 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.

To evaluate changes in treatment outcomes and epidemiologic profiles of gestational trophoblastic neoplasia (GTN) patients over a 20-year period.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 values0.05 considered statistically significant.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).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.

BACKGROUND The incidence of hydatidiform mole (HM) differs among regions but has declined significantly over time. In Thailand, the initiation of universal health coverage in 2002 has resulted in a change of medical services countrywide. However, impacts of these policies on gestational trophoblastic disease (GTD) cases in Thailand have not been reported. This study aimed to find the incidence of hydatidiform mole (HM) in King Chulalongkorn Memorial Hospital (KCMH) from 1994-2013, comparing before and after the implementation of the universal coverage health policy. MATERIALS AND METHODS All cases of GTD in KCMH from 1994-2013 were reviewed from medical records. The incidence of HM, patient characteristics, treatment and remission rates were compared over two study decades between 1994-2003 and 2004-2013. RESULTS Hydatidiform mole cases decreased from 204 cases in the first decade to 111 cases in the seond decade. Overall incidence of HM was 1.70 per 1,000 deliveries. The incidence of HM in the first and second decades were 1.70 and 1.71 per 1,000 deliveries, respectively (p=0.65, 95%CI 1.54-1.88). Referred cases of nonmolar gestational trophoblastic neoplasia (GTN) increased from 12 (4.4%) to 23 (14.4%, p

To study the correlation between serum and urine hCG levels in gestational trophoblastic disease (GTD) patients with low hCG level. The correlation between serum hCG and results from urine pregnancy tests are evaluated along with quantitative measurement.In this prospective study, 86 cases of gestational trophoblastic disease patients with positive and low level of serum hCG (100 mIU/ml) were recruited. Quantitative serum hCG urine hCG and urine pregnancy test were performed. The correlation coefficients between serum and urine hCG were then analyzed by SPSS 16.0. Furthermore, the levels of serum hCG were compared to the results of the urine pregnancy test.From February 2006 to June 2008, 86 cases were recruited for this study. The correlation coefficient between serum and urine hCG levels in all cases was 0.44 (using Pearson correlation), p = 0.01. In subgroup analysis, the correlation coefficient between serum and urine hCG levels in chemosensitive gestational trophoblastic neoplasia (GTN) patients (n = 27) was 0.73, p ≤ 0.01. The correlation coefficient in chemoresistant GTN patients (n = 38) was 0.29, p = 0.07; and the correlation coefficient in hydatidiform mole patients (n = 21) was 0.47, p = 0.03. A urine pregnancy test was positive only in 10 of 86 specimens.The correlation coefficient between serum and urine hCG in GTD patients with low hCG level showed significant correlation. However, patients with chemoresistance had less correlation than those with chemosensitivity and hydatidiform mole. Urine pregnancy test had low correlation with urine hCG and was not useful in this group of patients.

Background Gestational trophoblastic neoplasia (GTN) is a malignant disease which occurs in women of reproductive age. Treatment of GTN has an excellent outcome and further pregnancies can be expected. However, data concerning quality of life in these cancer survivor patients are limited. This study aimed to assess quality of life in women who were diagnosed with GTN and remission after treatment, and to determine factors that may affect quality of life status. Materials and methods This cross sectional study was conducted from July 2013 to May 2014 in the Gestational Trophoblastic Disease Clinic, King Chulalongkorn Memorial Hospital, Bangkok, Thailand. Patients who were diagnosed GTN and complete remission were recruited. Data collection was accomplished by interview with two sets of questionnaires, one general covering demographic data and the other focusing on quality of life, the fourth version of Functional Assessment of Cancer Therapy (FACT-G). Descriptive statistics were used to determine general data and quality of life scores. Students t-test and one way ANOVA were used to compare between categorical and continuous data. Results Forty four patients were enrolled in this study. The overall mean quality of life score (FACT-G) was 98.2. The overall FACT-G score was not significantly correlated with age, education level, stage of disease, treatment modalities, and time interval from remission to enrollment. However, patients who needed further fertility showed significant lower FACT-G scores in the emotional well-being domain (p=0.02). Conclusions Overall quality of life scores in post-treatment gestational trophoblastic neoplasia patients are in the mild impairment range. Patients who desire fertility suffer lower quality of life in the emotional well-being domain.

Objective. To study the potential of long interspersed element-1 (LINE-1) methylation change in the prediction of postmolar gestational trophoblastic neoplasia (GTN).Methods. The LINE-1 methylation pattern from first trimester placenta, hydatidiform mole, and malignant trophoblast specimens were compared. Then, hydatidiform mole patients from 11999 to 2010 were classified into the following 2 groups: a remission group and a group that developed postmolar GTN. Specimens were prepared for a methylation study. The methylation levels and percentages of LINE-1 loci were evaluated for their sensitivity, specificity, and accuracy for the prediction of postmolar GTN.Results. First, 12 placentas, 38 moles, and 19 malignant trophoblast specimens were compared. The hydatidiform mole group had the highest LINE-1 methylation level (p= 0.003) and theuCuC of LINE-1 increased in the malignant trophoblast group (p≤ 0.001). One hundred forty-five hydatidiform mole patients were classified as 103 remission and 42 postmolar GTN patients. The %mCuC and %uCmC of LINE-1 showed the lowestpvalue for distinguishing between the two groups (p< 0.001). The combination of the pretreatmentβ-hCG level (≥100,000 mIU/mL) with the %mCuC and %uCmC, sensitivity, specificity, PPV, NPV, and accuracy modified the levels to 60.0%, 92.2%, 77.4%, 83.8%, and 82.3%, respectively.Conclusions. A reduction in the partial methylation of LINE-1 occurs early before the clinical appearance of malignant transformation. The %mCuC and %uCmC of LINE-1s may be promising markers for monitoring hydatidiform moles before progression to GTN.

Background: Gestational trophoblastic neoplasia (GTN) is a spectrum of disease with abnormal trophoblastic proliferation. Treatment is based on FIGO stage and WHO risk factor scores. Patients whose score is 12 or more are considered as at extremely high risk with a high likelihood of resistance to first line treatment. Optimal therapy is therefore controversial. Objective: This study was conducted in order to summarize the regimen used for extremely high risk or resistant GTN patients in our institution the in past 10 years. Materials and Methods: All the charts of GTN patients classified as extremely high risk, recurrent or resistant during 1 January 2002 to 31 December 2011 were reviewed. Criteria for diagnosis of GTN were also assessed to confirm the diagnosis. FIGO stage and WHO risk prognostic score were also re-calculated to ensure the accuracy of the information. Patient characteristics were reviewed in the aspects of age, weight, height, BMI, presenting symptoms, metastatic area, lesions, FIGO stage, WHO risk factor score, serum hCG level, treatment regimen, adjuvant treatments, side effects and response to treatment, including disease free survival. Results: Eight patients meeting the criteria of extremely high risk or resistant GTN were included in this review. Mean age was 33.6 years (SD= 13.5, range 17-53). Of the total, 3 were stage III (37.5%) and 5 were stage IV (62.5%). Mean duration from previous pregnancies to GTN was 17.6 months (SD 9.9). Mean serum hCG level was 864,589 mIU/ml (SD 98,151). Presenting symptoms of the patients were various such as hemoptysis, abdominal pain, headache, heavy vaginal bleeding and stroke. The most commonly used first line chemotherapeutic regimen in our institution was the VAC regimen which was given to 4 of 8 patients in this study. The most common second line chemotherapy was EMACO. Adjuvant radiation was given to most of the patients who had brain metastasis. Most of the patients have to delay chemotherapy for 1-2 weeks due to grade 2-3 leukopenia and require G-CSF to rescue from neutropenia. Five form 8 patients were still survived. Mean of disease free survival was 20.4 months. Two patients died of the disease, while another one patient died from sepsis of pressure sore wound. None of surviving patients developed recurrence of disease after complete treatment. Conclusions: In extremely high risk GTN patients, main treatment is multi-agent chemotherapy. In our institution, we usually use VAC as a first line treatment of high risk GTN, but since resistance is quite common, this may not suitable for extremely high risk GTN patients. The most commonly used second line multi-agent chemotherapy in our institution is EMA-CO. Adjuvant brain radiation was administered to most of the patients with brain metastasis in our institution. The survival rate is comparable to previous reviews. Our treatment demonstrated differences from other institutions but the survival is comparable. The limitation of this review is the number of cases is small due to rarity of the disease. Further trials or multicenter analyses may be considered.

To investigate the role of PTEN and MDM2 expression in hydatidiform mole in the prediction of postmolar gestational trophoblastic neoplasia (GTN).A total of 145 cases of hydatidiform mole were diagnosed at the King Chulalongkorn Memorial Hospital from 1999 to 2010. Patients were classified into 2 groups: spontaneous remission and patients with postmolar GTN. Clinicopathologic features and immunohistochemical staining by PTEN and MDM2 were reviewed. The results were analyzed in correlation to the clinical characteristics and outcomes.Of 145 recruited cases, 128 (88.3%) cases were complete hydatidiform mole (CHM) and 17 (11.7%) cases were partial hydatidiform mole (PHM). Postmolar GTN was clinically diagnosed in 42 cases (28.9%). The incidences of postmolar GTN following CHM and PHM were 29.7% and 23.5%, respectively. Mean age of the postmolar GTN group was significantly older than that of the remission group (31.2 vs. 27.8, p = 0.04). There was no significant difference of pathologic features between cases with remission and postmolar GTN. Immunoreactivity of PTEN and MDM2 were similarly present in trophoblastic cells of both CHM and PHM groups without significantly different patterns.Immunohistochemical expression of PTEN and MDM2 in hydatidiform mole cannot predict molar malignant transformation.

To determine the correlation between serum placental growth factor (PlGF) and human chorionic gonadotropin (hCG) in patients with gestational trophoblastic disease (GTD) and to compare serum levels of PlGF in patients with gestational trophoblastic neoplasia to those of patients with hydatidiform mole.Blood and urine samples were collected from GTD patients. Blood and urine levels for PlGF were processed and quantitated by enzyme-linked immunosorbent assay in parallel with serum levels for hCG. Correlation levels of serum PlGF and hCG were analyzed. Serum levels of PlGF and hCG were correlated with the clinical manifestations of GTD.The correlation between serum levels of PlGF and hCG was not linear (r = 0.274, p = 0.229). The median PlGF levels in benign and malignant groups were 24.0 and 38.3 pg/mL, respectively (p = 0.014). The median serum hCG levels in benign and malignant groups were 7,335.0 and 9,974.5 mlU/mL, respectively (p = 0.942). The linear correlation between urine and serum levels for PlGF was not detected (r = 0.064).Levels of correlation for serum PlGF and hCG in GTD patients were not linear. Median serum levels of PlGF between benign and malignant groups were significantly different. This suggests that there is a higher production of PlGF levels in patients with choriocarcinoma or malignant GTD.

To determine intrauterine pathology in patients with postmolar gestational trophoblastic neoplasia (GTN) and hydatidiform mole after suction curettage. Safety profiles of endometrial sampling in this setting are also evaluated.In this prospective study, 24 cases with persistent GTN or postevacuation hydatidiform mole were recruited. Endometrial pathology was evaluated by Endocell. Clinical characteristics, safety of the instrument and pathology results were analyzed.During August 2006 to July 2007, 15 cases with postmolar GTN and 9 cases of postevacuation mole were recruited. Of 15 cases of postmolar GTN, 2 (13%) showed molar tissue. All 9 cases of postevacuation hydatidiform mole showed benign endometrial tissue or normal trophoblast in endometrial sampling pathology. No patients in this study had severe vaginal bleeding or infection after endometrial sampling. Analysis of endometrial sampling pathology as a diagnostic test for GTN showed a sensitivity of 0.133 (95% CI 0.037-0.379).Endometrial sampling by Endocell is safe in patients with gestational trophoblastic disease. Although the pathology findings from endometrial sampling had low sensitivity in diagnosing GTN, we encourage a larger prospective trial to confirm this result.

Pregnancy in the broad ligament is a rare form of ectopic pregnancy, and one type of abdominal pregnancy. The diagnosis is seldom established before surgery. A 38-year-old, 11-week pregnant woman, gravida 3, para 2, presented with vaginal bleeding. She had undergone two cesarean sections 10 and 6 years earlier. Pregnancy in the right broad ligament was diagnosed from clinical and transvaginal ultrasonographic findings. Emergency laparotomy and excision of a pregnancy in the right broad ligament and right salpingectomy were performed. She was well at discharge and at the 6-week follow up. We suggest the use of clinical and ultrasonographic findings for the suspicion of pregnancy in the broad ligament.