LAWRENCE HSU LIN
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/57 - Laboratório de Fisiologia Obstétrica, Hospital das Clínicas, Faculdade de Medicina
LIM/57 - Laboratório de Fisiologia Obstétrica, Hospital das Clínicas, Faculdade de Medicina
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- Is Doppler ultrasound useful for evaluating gestational trophoblastic disease?(2015) LIN, Lawrence H.; BERNARDES, Lisandra S.; HASE, Eliane A.; FUSHIDA, Koji; FRANCISCO, Rossana P. V.Doppler ultrasound is a non-invasive method for evaluating vascularization and is widely used in clinical practice. Gestational trophoblastic neoplasia includes a group of highly vascularized malignancies derived from placental cells. This review summarizes data found in the literature regarding the applications of Doppler ultrasound in managing patients with gestational trophoblastic neoplasia. The PubMed/Medline, Web of Science, Cochrane and LILACS databases were searched for articles published in English until 2014 using the following keywords: ""Gestational trophoblastic disease AND Ultrasonography, Doppler."" Twenty-eight articles met the inclusion criteria and were separated into the 4 following groups according to the aim of the study. (1) Doppler ultrasound does not seem to be capable of differentiating partial from complete moles, but it might be useful when evaluating pregnancies in which a complete mole coexists with a normal fetus. (2) There is controversy in the role of uterine artery Doppler velocimetry in the prediction of development of gestational trophoblastic neoplasia. (3) Doppler ultrasound is a useful tool in the diagnosis of gestational trophoblastic neoplasia because abnormal myometrial vascularization and lower uterine artery Doppler indices seem to be correlated with invasive disease. (4) Lower uterine artery Doppler indices in the diagnosis of gestational trophoblastic neoplasia are associated with methotrexate resistance and might play a role in prognosis. CONCLUSION: Several studies support the importance of Doppler ultrasound in the management of patients with gestational trophoblastic neoplasia, particularly the role of Doppler velocimetry in the prediction of trophoblastic neoplasia and the chemoresistance of trophoblastic tumors. Doppler findings should be used as ancillary tools, along with human chorionic gonadotropin assessment, in the diagnosis of gestational trophoblastic neoplasia.
- Multiple pregnancies with complete mole and coexisting normal fetus in North and South America: A retrospective multicenter cohort and literature review(2017) LIN, Lawrence H.; MAESTA, Izildinha; BRAGA, Antonio; SUN, Sue Y.; FUSHIDA, Koji; FRANCISCO, Rossana P. V.; ELIAS, Kevin M.; HOROWITZ, Neil; GOLDSTEIN, Donald P.; BERKOWITZ, Ross S.Objective. To determine the clinical characteristics of multiple gestation with complete mole and coexisting fetus (CHMCF) in North and South America. Methods. Retrospective non-concurrent cohorts compromised of CHMCF from New England Trophoblastic Disease Center (NETDC) (1966-2015) and four Brazilian Trophoblastic Disease Centers (BTDC) (1990-2015). Results. From a total of 12,455 cases of gestational trophoblastic disease seen, 72 CHMCF were identified. Clinical characteristics were similar between BTDC (n = 46) and NETDC (n = 13) from 1990 to 2015, apart from a much higher frequency of potentially life-threatening conditions in Brazil (p = 0.046). There were no significant changes in the clinical presentation or outcomes over the past 5 decades in NETDC (13 cases in 1966-1989 vs 13 cases in 1990-2015). Ten pregnancies were electively terminated and 35 cases resulted in viable live births (60% of 60 continued pregnancies). The overall rate of gestational trophoblastic neoplasia (GTN) was 46%; the cases which progressed to GTN presented with higher chorionic gonadotropin levels (p = 0.026) and higher frequency of termination of pregnancy due to medical complications (p = 0.006) when compared to those with spontaneous remission. Conclusions. The main regional difference in CHMCF presentation is related to a higher rate of potentially life threatening conditions in South America. Sixty percent of the expectantly managed CHMCF delivered a viable infant, and the overall rate of GTN in this study was 46%. Elective termination of pregnancy did not influence the risk for GTN; however the need for termination due to complications and higher hCG levels were associated with development of GTN in CHMCF.
article 3 Citação(ões) na Scopus Management of Symptomatic Uterine Arteriovenous Malformations After Gestational Trophoblastic Disease The Brazilian Experience and Possible Role for Depot Medroxyprogesterone Acetate and Tranexamic Acid Treatment(2018) BRAGA, Antonio; LIMA, Lana; PARENTE, Raphael Camara Medeiros; CELESTE, Roger Keller; REZENDE FILHO, Jorge de; AMIM JUNIOR, Joffre; MAESTA, Izildinha; SUN, Sue Yazaki; UBERTI, Elza; LIN, Lawrence; MADI, Jose Mauro; VIGGIANO, Mauricio; ELIAS, Kevin M.; HOROWITZ, Neil S.; BERKOWITZ, Ross S.OBJECTIVE: To identify predictive variables of heavy vaginal bleeding from uterine arteriovenous malformation (uAVM) after gestational trophoblastic disease (GTD) and review outcomes with different treatment strategies. STUDY DESIGN: This is a retrospective study of patients with uAVM presenting with vaginal bleeding after postmolar follow-up or treatment for postmolar gestational trophoblastic neoplasia, with normal hCG levels for at least 6 or 12 months, respectively, followed at 9 Brazilian GTD reference centers, from January 2004-January 2016. Patients were treated preferentially with uterine artery embolization (UAE), but when UAE was not available, depot medroxyprogesterone acetate and tranexamic acid (DMPA + TA) was offered. RESULTS: The incidence of symptomatic uAVM after GTD was 0.6% (39/6,129). Risk factors associated with class III-IV hemorrhage included number of previous curettages (aRR 4.23, 95% CI 1.36-13.1, p=0.013), uterine artery index of resistance <= 0.32 (aRR 35.2, 95% CI 3.58-347.5, p=0.002), and uterine artery peak systolic velocity >= 78.7 cm/s (aRR 10.7, 95% CI 1.15-100.6, p=0.037). Patients with class I-II hemorrhage treated with DMPA + TA had a higher rate of uAVM resolution (N=14/16 [87.5%]) versus UAE (N=4/8 [50%], p=0.033). Patients with class III-IV hemorrhage were 87% less likely to have successful treatment with DMPA + TA compared to class I-II hemorrhage (cRR 0.13, 95% CI 0.02-0.83, p=0.013). CONCLUSION: Although UAE is preferred for cases of heavy vaginal bleeding, there may be a role for DMPA + TA in the management of less severe bleeding complications.- Fetal-Maternal Hemorrhage in First-Trimester Intrauterine Hematoma(2021) NARCISO, Thaisa A. R. M.; HOSHIDA, Mara S.; COSTA, Priscilla R.; NIQUIRILO, Andrea; BIANCOLIN, Sckarlet E.; LIN, Lawrence H.; FRANCISCO, Rossana P. V.; BRIZOT, Maria L.Objective: The objective of this study was to compare the frequency and percentage of fetal hemoglobin (HbF%) by flow cytometry of (1) first-trimester asymptomatic patients with intrauterine hematoma (IUH), (2) first-trimester pregnant patients with vaginal bleeding (VB), and (3) first-trimester asymptomatic pregnant women without hematoma. Methods: Prospective study involving pregnant women in the first trimester of pregnancy. Patients with ultrasound findings of asymptomatic hematoma and with VB were paired with asymptomatic pregnant women of same gestational age without hematoma (control group [CG]). Maternal blood HbF% was evaluated by flow cytometry. The groups were compared in terms of circulating fetal hemoglobin and HbF%. Results: Sixty-six patients were selected, 22 with hematoma, 17 with bleeding, and 27 in the CG. Fetal hemoglobin was detected in 15 patients with hematoma (68.2%) and 13 with bleeding (76.5%) and in 20 of the control (74.1%) (p = 0.830). The mean HbF% of each group was 0.054, 0.012, and 0.042 for hematoma, bleeding, and control, respectively, and differences were not significant (p = 0.141). There was a moderate negative correlation between the volume of hematoma and HbF% (r(Spearman) = -0.527; p = 0.012). Conclusions: The fetal-maternal hemorrhage expressed by Hbf% in first-trimester pregnancies did not seem to differ between patients with and without ultrasound findings of IUH.
- Is chemotherapy necessary for patients with molar pregnancy and human chorionic gonadotropin serum levels raised but falling at 6 months after uterine evacuation?(2016) BRAGA, Antonio; TORRES, Berenice; BURLA, Marcelo; MAESTA, Izildinha; SUN, Sue Yazaki; LIN, Lawrence; MADI, Jose Mauro; UBERTI, Elza; VIGGIANO, Mauricio; ELIAS, Kevin M.; BERKOWITZ, Ross S.Objective. To compare the outcomes of Brazilian patients with molar pregnancy who continue human chorionic gonadotropin (hCG) surveillance with those treated with chemotherapy when hCG was still positive, but falling at 6 months after uterine evacuation. Methods. Retrospective chart review of 12,526 patients with hydatidiform mole treated at one of nine Brazilian reference centers from January 1990 to May 2016. Results. At 6 months from uterine evacuation', 96 (0.8%) patients had hCG levels raised but falling. In 15/96 (15.6%) patients, chemotherapy was initiated immediately per FIGO 2000 criteria, while 81/96 (84.4%) patients were managed expectantly. Among the latter, 65/81 (80.2%) achieved spontaneous remission and 16 (19.8%) developed postmolar gestational trophoblastic neoplasia (GTN). Patients who received chemotherapy following expectant management required more time for remission (11 versus 8 months; p = 0.001), had a greater interval between uterine evacuation and initiating chemotherapy (8 versus 6 months; p < 0.001), and presented with a median WHO/FIGO risk score higher than women treated according to FIGO 2000 criteria (4 versus 2, p = 0.04), but there were no significant differences in the need for multiagent treatment regimens (1/15 versus 3/16 patients, p = 0.60). None of the women relapsed, and no deaths occurred in either group. Conclusion. In order to avoid unnecessary exposure of women to chemotherapy, we no longer follow the FIGO 2000 recommendation to treat all patients with molar pregnancy and hCG raised but falling at 6 months after evacuation. Instead, we pursue close hormonal and radiological surveillance as the best strategy for these patients.
- Is chemotherapy always necessary for patients with nonmetastatic gestational trophoblastic neoplasia with histopathological diagnosis of choriocarcinoma?(2018) BRAGA, Antonio; CAMPOS, Vanessa; REZENDE FILHO, Jorge; LIN, Lawrence H.; SUN, Sue Yazaki; SOUZA, Christiani Bisinoto de; SILVA, Rita de Cassia Alves Ferreira da; LEAL, Elaine Azevedo Soares; SILVEIRA, Eduardo; MAESTA, Izildinha; MADI, Jose Mauro; UBERTI, Elza H.; VIGGIANO, Mauricio; ELIAS, Kevin M.; HOROWITZ, Neil; BERKOWITZ, Ross S.Objective. To evaluate expectant management versus immediate chemotherapy following pathological diagnosis of gestational choriocarcinoma (GCC) in patients with nonmetastatic disease. Methods. Multicenter retrospective cohort that included patients with histological diagnosis of GCC with nonmetastatic disease followed at one of thirteen Brazilian referral centers for gestational trophoblastic disease from January 2000 to December 2016. Results. Among 3191 patients with gestational trophoblastic neoplasia, 199 patients with nonmetastatic GCC were identified. Chemotherapy was initiated immediately in 152 (76.4%) patients per FIGO 2000 guideline, while 47 (23.6%) were managed expectantly. Both groups presented with similar characteristics and outcomes. All patients (n = 12) who had normal human chorionic gonadotropin (hCG) in the first 2-3 weeks of expectant management achieved complete sustained remission with no chemotherapy. Only 44.7% (21 patients) of patients who were expectantly managed needed to receive chemotherapy due to plateauing or rising hCG level in the first 2-3 weeks of follow up. The outcome of patients receiving chemotherapy after initial expectant management was similar to those who received chemotherapy immediately after the diagnosis in terms of need for multi-agent chemotherapy or number of cycles of chemotherapy. There was no case of relapse or death in either group. Logistic regression analysis showed that age >= 40 years and hCG >= 92,428 IU/L at GCC diagnosis were risk factors for needing chemotherapy after initial expectant management of nonmetastatic GCC. Conclusion. In order to avoid exposing patients unnecessarily to chemotherapy, close surveillance of women with pathological diagnosis of nonmetastatic GCC seems to be a safe practice, particularly for those who have a normal hCG at the time of diagnosis. If confirmed by other studies, the FIGO guidelines may need to be revised.
- Pregnancy outcomes after chemotherapy for trophoblastic neoplasia(2016) GARCIA, MILA TREMENTOSA; LIN, LAWRENCE HSU; FUSHIDA, KOJI; FRANCISCO, ROSSANA PULCINELI VIEIRA; ZUGAIB, MARCELOSUMMARY Introduction The successful development of chemotherapy enabled a fertilitysparing treatment for patients with trophoblastic neoplasia. After disease remission, the outcome of a subsequent pregnancy becomes a great concern for these women. Objective To analyze existing studies in the literature that describe the reproductive outcomes of patients with trophoblastic neoplasia treated with chemotherapy. Method Systematic review was performed searching for articles on Medline/ Pubmed, Lilacs and Cochrane Library databases, using the terms “gestational trophoblastic disease” and “pregnancy outcome”. Results A total of 18 articles were included. No evidence of decreased fertility after chemotherapy for trophoblastic neoplasia was observed. The abortion rates in patients who conceived within 6 months after chemotherapy was higher compared to those who waited longer. Some studies showed increased rates of stillbirth and repeat hydatidiform moles. Only one work showed increased congenital abnormalities. Conclusion The pregnancies conceived after chemotherapy for trophoblastic neoplasia should be followed with clinical surveillance due to higher rates of some pregnancy complications. However, studies in the literature provide reassuring data about reproductive outcomes of these patients.
- Impact of clinical characteristics on human chorionic gonadotropin regression after molar pregnancy(2021) GOCKLEY, Allison A.; LIN, Lawrence H.; DAVIS, Michelle; MELAMED, Alexander; RIZZO, Anthony; SUN, Sue Yazaki; ELIAS, Kevin; GOLDSTEIN, Donald P.; BERKOWITZ, Ross S.; HOROWITZ, Neil S.OBJECTIVES: This study aimed to determine the effects of age, race/ethnicity, body mass index, and contraception on human chorionic gonadotropin (hCG) regression following the evacuation of a molar pregnancy. METHODS: This was a retrospective cohort study of 277 patients with molar pregnancies between January 1, 1994 and December 31, 2015. The rate of hCG regression was estimated using mixed-effects linear regression models on daily log-transformed serum hCG levels after evacuation. RESULTS: There were no differences in hCG half-lives among age (p=0.13) or race/ethnicity (p=0.16) groups. Women with obesity and hormonal contraceptive use demonstrated faster hCG regression than their counterparts (3.2 versus. 3.7 days, p=0.02 and 3.4 versus. 4.0 days, p=0.002, respectively). CONCLUSION: Age and race/ethnicity were not associated with hCG regression rates. Hormonal contraceptive use and obesity were associated with shorter hCG half-lives, but with unlikely clinical significance. It is important to understand whether the clinical characteristics of patients may influence the hCG regression curve, as it has been proposed as a way to predict the risk of gestational trophoblastic neoplasia.
- Imaging in Gestational Trophoblastic Disease(2019) LIN, Lawrence Hsu; POLIZIO, Rodrigo; FUSHIDA, Koji; FRANCISCO, Rossana Pulcineli VieiraGestational trophoblastic disease (GTD) is a spectrum of disorders characterized by abnormal trophoblastic proliferation. GTD includes benign conditions such as hydatidiform moles and malignant diseases that are referred as gestational trophoblastic neoplasia (GTN). Ultrasound plays a central role in the diagnosis of patients with hydatidiform mole. Other imaging modalities are useful in molar pregnancy, mainly for evaluating pulmonary complications and atypical presentation of hydatidiform mole. GTN typically arises after 20% of molar pregnancies but can uncommonly occur after nonmolar gestations. After uterine evacuation, serial human chorionic gonadotropin levels are evaluated in patients for early detection of GTN. Once GTN is suspected, Doppler ultrasound is the primary tool to confirm the diagnosis; however, magnetic resonance imaging can also help in selected cases. Metastatic disease workup can involve various modalities, including ultrasound, X-ray, computed tomography, magnetic resonance imaging and positron emission tomography/computed tomography. In this article, we review the main imaging modalities used to evaluate patients with GTD.
- Loss of Selenoprotein Iodothyronine Deiodinase 3 Expression Correlates with Progression of Complete Hydatidiform Mole to Gestational Trophoblastic Neoplasia(2021) LAURENT, Jessica D. St; LIN, Lawrence H.; OWEN, David M.; MAESTA, Izildinha; CASTANEDA, Arnold; HASSELBLATT, Kathleen T.; GOLDSTEIN, Donald P.; HOROWITZ, Neil S.; BERKOWITZ, Ross S.; ELIAS, Kevin M.To investigate if differences in imprinting at tropho-microRNA (miRNA) genomic clusters can distinguish between pre-gestational trophoblastic neoplasia cases (pre-GTN) and benign complete hydatidiform mole (CHM) cases at the time of initial uterine evacuation. miRNA sequencing was performed on frozen tissue from 39 CHM cases including 9 GTN cases. DIO3, DLK1, RTL1, and MEG 3 mRNA levels were assessed by qRT-PCR. Protein abundance was assessed by Western blot for DIO3, DLK1, and RTL1. qRT-PCR and Western blot were performed for selenoproteins and markers of oxidative stress. Immunohistochemistry (IHC) was performed for DIO3 on an independent validation set of clinical samples (n = 42) and compared to normal placenta controls across gestational ages. Relative expression of the 14q32 miRNA cluster was lower in pre-GTN cases. There were no differences in protein abundance of DLK1 or RTL1. Notably, there was lower protein expression of DIO3 in pre-GTN cases (5-fold, p < 0.03). There were no differences in mRNA levels of DIO3, DLK1, RTL1 or MEG 3. mRNA levels were higher in all CHM cases compared to normal placenta. IHC showed syncytiotrophoblast-specific DIO3 immunostaining in benign CHM cases and normal placenta, while pre-GTN cases of CHM lacked DIO3 expression. We describe two new biomarkers of pre-GTN CHM cases: decreased 14q32 miRNA expression and loss of DIO3 expression by IHC. Differences in imprinting between benign CHM and pre-GTN cases may provide insight into the fundamental development of CHM.