RESUMO
OBJECTIVE: To examine the prevalence and prognostic role of tumor microenvironment (TME) markers in uterine carcinosarcoma (UCS) through immunohistochemical characterization. METHODS: The internal database of our institution was queried out for women with UCS who underwent surgery and thereafter postoperative chemotherapy with carboplatin and paclitaxel between January 2012 and December 2017. Tissue microarrays containing surgical samples of UCS from 57 women were assessed by immunohistochemistry for CD3, CD4, CD8, FOXP3, PD-1, PD-L1, and PD-L2. RESULTS: The mean age was 65.3 years (range, 49 to 79 years). For the epithelial component (E), CD3_E and CD4_E were highly expressed in 38 (66.7%) and in 40 (70.1%) patients, respectively, and were significantly associated with more advanced stages (p = 0.038 and p = 0.025, respectively). CD8_E was highly expressed in 42 (73.7%) patients, FOXP3_E 16 (28.1%), PD-1_E 35 (61.4%), PD-L1_E 27 (47.4%) and PD-L2_E 39 (68.4%). For the sarcomatous component (S), the prevalence of high expression was: CD3_S 6 (10.5%), CD4_S 20 (35.1%), CD8_S 44 (77.2%), FOXP3_S 8 (14%), PD-1_S 14 (24.6%), PD-L1_S 14 (24.6%) and PD-L2_S 8 (14%). By multivariate analysis, the CD8/FOXP3_S ratio (p = 0.026), CD4_E (p = 0.010), PD-L1_E (p = 0.013) and PD-L1_S (p = 0.008) markers significantly influenced progression-free survival. CD4/FOXP3_S ratio (p = 0.043), PD-1_E (p = 0.011), PD-L1_E (p = 0.036) and PD-L1_S (p = 0.028) had a significant association with overall survival. CONCLUSION: Some differences in UCS clinical outcomes may be due to the subtype of TILs and PD-1/PD-L1 axis immune checkpoint signaling.
Assuntos
Carcinossarcoma/imunologia , Carcinossarcoma/mortalidade , Linfócitos do Interstício Tumoral/metabolismo , Neoplasias Uterinas/imunologia , Neoplasias Uterinas/mortalidade , Idoso , Antineoplásicos/uso terapêutico , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/imunologia , Carboplatina/uso terapêutico , Carcinossarcoma/sangue , Feminino , Regulação Neoplásica da Expressão Gênica/imunologia , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Paclitaxel/uso terapêutico , Prevalência , Prognóstico , Receptor de Morte Celular Programada 1/metabolismo , Transdução de Sinais/imunologia , Microambiente Tumoral/imunologia , Neoplasias Uterinas/sangueRESUMO
OBJECTIVE: To compare the effect of high-dose vitamin A (HD Vit-A) use during postmolar follow-up of patients with low and plateauing (L&P) serum human chorionic gonadotropin (hCG) levels, from the moment serum hCG plateaued (P-hCG) to the first normal serum hCG value (< 5 IU/L). METHODS: The present retrospective series case study compared two nonconcurrent cohorts of patients. Control group (CG): 34 patients with L&P serum hCG levels who underwent expectant management for 6 months after uterine evacuation, from 1992 to 2010; study group (SG): 32 patients in similar conditions who received 200,000 IU of Vit-A daily, from the identification of a P-hCG level to the first normal hCG value or the diagnosis of progression to gestational trophoblastic neoplasia (GTN), from 2011 to 2017. The present study was approved by the Ethics Committee of the institution where it was conducted. RESULTS: In both groups, the prevalence of persistent L&P serum hCG levels was < 5%. In the SG, hCG levels at plateau were higher (CG = 85.5 versus SG = 195 IU/L; p = 0.028), the rate of postmolar GTN was lower (CG = 29.4% versus SG = 6.3%, p = 0.034) and follow-up was shorter (CG = 14 versus SG = 10 months, p < 0.001). During GTN follow-up, there were no differences in GTN staging or treatment aggressiveness in both groups. High-dose Vit-A use did not have any relevant toxic effect. There were no GTN relapses or deaths. CONCLUSION: The limited use of HD Vit-A seems to have a safe and significant effect on the treatment of postmolar patients with L&P serum hCG levels and may decrease the development of postmolar GTN in this population.
OBJETIVO: Comparar o efeito de alta dose de vitamina A (VitA) no seguimento pós-molar de pacientes com gonadotrofina coriônica humana (hCG) sérica apresentando valores baixos e em platô (L&P). MéTODOS: Estudo retrospectivo de série de casos comparando duas coortes não simultâneas. Grupo controle (CG): 34 pacientes com títulos de hCG sérico L&P submetidos a manejo expectante por 6 meses após o esvaziamento uterino, de 1992 a 2010; Grupo de Estudo (SG): de 2011 a 2017, 32 pacientes em condições semelhantes de hCG receberam Vit-A na dose de 200.000 IU por dia, do momento da identificação do hCG em platô ate o primeiro hCG normal ou diagnóstico de progressão para neoplasia trofoblástica gestacional (NTG). O presente estudo foi aprovado pelo Comitê de Ética da Instituição na qual foi desenvolvido. RESULTADOS: Em ambos os grupos, a prevalência de hCG L&P foi < 5%. No SG, os níveis de hCG em platô foram maiores (CG = 85.5 versus SG = 195 IU/L; p = 0,028), e foram significantemente menores tanto a prevalência de NTG pós-molar (CG = 29.4% versus SG = 6.3%, p = 0,034) como o tempo de seguimento (CG = 14 versus SG = 10 meses, p < 0.001). Na evolução para NTG não houve diferença no estadiamento da International Federation of Gynecology and Obstetrics (FIGO, na sigla em inglês) ou na agressividade do tratamento. Com altas doses de Vit-A não houve qualquer efeito tóxico relevante. Não houve casos de recidiva de NTG ou de óbito. CONCLUSãO: O uso limitado de altas doses de Vit-A parace ser seguro e apresenta efeitos significativos na evolução de pacientes em controle pós-molar com títulos de hCG sérico L&P, e pode diminuir o desenvolvimento de NTG pós-molar nessa população.
Assuntos
Gonadotropina Coriônica/sangue , Mola Hidatiforme/sangue , Neoplasias Uterinas/sangue , Vitamina A/uso terapêutico , Adolescente , Adulto , Biomarcadores Tumorais/sangue , Feminino , Doença Trofoblástica Gestacional/prevenção & controle , Humanos , Pessoa de Meia-Idade , Gravidez , Estudos Retrospectivos , Resultado do Tratamento , Vitamina A/administração & dosagem , Adulto JovemRESUMO
Abstract Objective To compare the effect of high-dose vitamin A (HD Vit-A) use during postmolar follow-up of patients with low and plateauing (L&P) serum human chorionic gonadotropin (hCG) levels, from the moment serum hCG plateaued (P-hCG) to the first normal serum hCG value (< 5IU/L). Methods The present retrospective series case study compared two nonconcurrent cohorts of patients. Control group (CG): 34 patients with L&P serum hCG levels who underwent expectant management for 6 months after uterine evacuation, from 1992 to 2010; study group (SG): 32 patients in similar conditions who received 200,000 IU of Vit-A daily, from the identification of a P-hCG level to the first normal hCG value or the diagnosis of progression to gestational trophoblastic neoplasia (GTN), from 2011 to 2017. The present study was approved by the Ethics Committee of the institution where it was conducted. Results In both groups, the prevalence of persistent L&P serum hCG levels was < 5%. In the SG, hCG levels at plateau were higher (CG = 85.5 versus SG = 195 IU/L; p = 0.028), the rate of postmolar GTN was lower (CG = 29.4% versus SG = 6.3%, p = 0.034) and follow-up was shorter (CG = 14 versus SG = 10 months, p < 0.001). During GTN follow-up, there were no differences in GTN staging or treatment aggressiveness in both groups. High-dose Vit-A use did not have any relevant toxic effect. There were no GTN relapses or deaths. Conclusion The limited use of HD Vit-A seems to have a safe and significant effect on the treatment of postmolar patients with L&P serum hCG levels and may decrease the development of postmolar GTN in this population.
Resumo Objetivo Comparar o efeito de alta dose de vitamina A (VitA) no seguimento pósmolar de pacientes com gonadotrofina coriônica humana (hCG) sérica apresentando valoresbaixoseem platô(L&P). Métodos Estudo retrospectivo de série de casos comparando duas coortes não simultâneas. Grupo controle (CG): 34 pacientes com títulos de hCG sérico L&P submetidos a manejo expectante por 6 meses após o esvaziamento uterino, de 1992 a 2010; Grupo de Estudo (SG): de 2011 a 2017, 32 pacientes em condições semelhantes de hCG receberam Vit-A na dose de 200.000 IU por dia, do momento da identificação dohCG em platôate o primeirohCG normaloudiagnóstico de progressão para neoplasia trofoblástica gestacional (NTG). O presente estudo foi aprovado pelo Comitê de Ética da Instituição na qual foi desenvolvido. Resultados Em ambososgrupos, aprevalência de hCGL&P foi < 5%. No SG, os níveis de hCGemplatô forammaiores (CG = 85.5 versus SG = 195 IU/L; p = 0,028), e foram significantemente menores tanto a prevalência de NTG pós-molar (CG = 29.4% versus SG = 6.3%, p = 0,034) como o tempo de seguimento (CG = 14 versus SG = 10 meses, p < 0.001). Na evolução para NTG não houve diferença no estadiamento da Interna tional Federation of Gynecology and Obstetrics (FIGO, na sigla em inglês) ou na agressividade do tratamento. Com altas doses de Vit-A não houve qualquer efeito tóxico relevante. Não houve casos de recidiva de NTG ou de óbito. Conclusão O uso limitado de altas doses de Vit-A parace ser seguro e apresenta efeitos significativos na evolução de pacientes em controle pós-molar com títulos de hCG sérico L&P, e pode diminuir o desenvolvimento de NTG pós-molar nessa população.
Assuntos
Humanos , Feminino , Gravidez , Adolescente , Adulto , Adulto Jovem , Neoplasias Uterinas/sangue , Vitamina A/uso terapêutico , Mola Hidatiforme/sangue , Gonadotropina Coriônica/sangue , Vitamina A/administração & dosagem , Biomarcadores Tumorais/sangue , Estudos Retrospectivos , Resultado do Tratamento , Doença Trofoblástica Gestacional/prevenção & controle , Pessoa de Meia-IdadeRESUMO
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.
Assuntos
Aborto Induzido/estatística & dados numéricos , Mola Hidatiforme/epidemiologia , Complicações Neoplásicas na Gravidez/epidemiologia , Gravidez de Gêmeos , Neoplasias Uterinas/epidemiologia , Aborto Espontâneo/epidemiologia , Adolescente , Adulto , Brasil/epidemiologia , Gonadotropina Coriônica/sangue , Estudos de Coortes , Feminino , Morte Fetal , Humanos , Mola Hidatiforme/sangue , Hipertireoidismo/epidemiologia , Nascido Vivo/epidemiologia , New England/epidemiologia , América do Norte , Pré-Eclâmpsia/epidemiologia , Gravidez , Complicações Neoplásicas na Gravidez/sangue , Gravidez Múltipla , Nascimento Prematuro/epidemiologia , Síndrome do Desconforto Respiratório/epidemiologia , Estudos Retrospectivos , América do Sul , Hemorragia Uterina/epidemiologia , Neoplasias Uterinas/sangue , Adulto JovemRESUMO
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 6months 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 6months 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 8months; p=0.001), had a greater interval between uterine evacuation and initiating chemotherapy (8 versus 6months; 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 6months after evacuation. Instead, we pursue close hormonal and radiological surveillance as the best strategy for these patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Gonadotropina Coriônica/sangue , Mola Hidatiforme/tratamento farmacológico , Neoplasias Uterinas/tratamento farmacológico , Curetagem a Vácuo , Conduta Expectante , Adolescente , Adulto , Brasil , Estudos de Casos e Controles , Quimioterapia Adjuvante , Estudos de Coortes , Ciclofosfamida/administração & dosagem , Dactinomicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Doença Trofoblástica Gestacional , Humanos , Mola Hidatiforme/sangue , Mola Hidatiforme/patologia , Leucovorina/administração & dosagem , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Gravidez , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias Uterinas/sangue , Neoplasias Uterinas/patologia , Vincristina/administração & dosagem , Adulto JovemRESUMO
OBJECTIVE: To report on the Brazilian Association of Gestational Trophoblastic Disease's (GTD) formation of a network of regional care at specialized centers for women with GTD. 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.
Assuntos
Atenção à Saúde/organização & administração , Países em Desenvolvimento , Doença Trofoblástica Gestacional/terapia , Ginecologia/estatística & dados numéricos , Obstetrícia/estatística & dados numéricos , Centros de Atenção Terciária/estatística & dados numéricos , Neoplasias Uterinas/terapia , Adulto , Brasil , Gonadotropina Coriônica/sangue , Feminino , Doença Trofoblástica Gestacional/sangue , Ginecologia/organização & administração , Humanos , Perda de Seguimento , Pessoa de Meia-Idade , Obstetrícia/organização & administração , Médicos/estatística & dados numéricos , Gravidez , Especialização , Inquéritos e Questionários , Centros de Atenção Terciária/organização & administração , Neoplasias Uterinas/sangueRESUMO
OBJECTIVE: To re-evaluate the safety of hormonal contraceptives (HC) after uterine evacuation of complete hydatidiform mole (CHM). DESIGN: Historical database review. SETTING: Charing Cross Hospital Gestational Trophoblastic Disease Centre, London, United Kingdom. POPULATION: Two thousand four hundred and twenty-three women with CHM of whom 154 commenced HC while their human chorionic gonadotropin (hCG) was still elevated, followed between 2003 and 2012. METHODS: We compared time to hCG remission between HC users and nonusers. The relationship between HC use and gestational trophoblastic neoplasia (GTN) development was assessed. The relationship between HC use and a high International Federation of Gynecology and Obstetrics (FIGO) risk score was determined. MAIN OUTCOME MEASURES: Time to hCG remission, risk of developing postmolar GTN and proportion of women with high FIGO risk score. RESULTS: No relationship was observed between HC use with mean time to hCG remission (HC users versus non-users: 12 weeks in both, P = 0.19), GTN development (HC users versus non-users: 20.1 and 16.7%, P = 0.26) or high-risk FIGO score (HC users versus nonusers: 0% and 8%, P = 0.15). Moreover, no association between HC and GTN development was found, even when an age-adjusted model was used (OR = 1.37, 95% CI 0.91-2.08, P = 0.13). CONCLUSIONS: The use of current HC is not associated with development of postmolar GTN or delayed time to hCG remission. Therefore, HC can be safely used to prevent a new conception following CHM regardless of hCG level. TWEETABLE ABSTRACT: Non-concurrent cohort study to re-evaluate the safety of low dose HCs after uterine evacuation of CHM.
Assuntos
Anticoncepcionais Orais Hormonais/uso terapêutico , Doença Trofoblástica Gestacional/epidemiologia , Mola Hidatiforme/cirurgia , Neoplasias Uterinas/cirurgia , Adolescente , Adulto , Gonadotropina Coriônica/sangue , Bases de Dados Factuais , Feminino , Humanos , Mola Hidatiforme/sangue , Pessoa de Meia-Idade , Razão de Chances , Gravidez , Estudos Retrospectivos , Fatores de Risco , Reino Unido/epidemiologia , Neoplasias Uterinas/sangue , Adulto JovemRESUMO
BACKGROUND: The etiology of uterine leiomyomatosis is multifactorial and it is unknown if a relation between anti-Müllerian hormone (hormona anti-mülleriana) and uterine leiomyomatosis exists. OBJECTIVE: To determine the differences of hormona anti-mülleriana levels in women with and without uterine leiomyomatosis. METHODS: 60 women were studied (30 with and 30 without uterine leiomyomatosis). The diagnosis was confirmed by histopathology. Both groups were paired by age and in all them serum levels of hormona antimülleriana were measured using ELISA, also estradiol and progesterone serum levels were determined. hormona anti-mülleriana-RII immunohistochemistry was done in healthy myometrium and in leiomyomas. RESULTS: The mean age between the groups didn't show statistical difference (41.8 +/- 5.6 years vs. 41.4 +/- 5.7 years). Also no differences were found in weight, height and body mass index. Serum levels of hormona antimülleriana were lower in those with leiomyomatosis [0.21 (0-10.4) ng/ml vs. 1.83 (0-6.38) ng/ml, p < 0.005]. No statistical differences were found in estradiol and progesterone serum levels between the groups. The hormona antimülleriana receptor was no expressed neither in the healthy myometrium nor in the leiomyomas. CONCLUSIONS: Women with leiomyomatosis had lower hormona antimülleriana levels. More studies are needed to determine if a relation exists between hormona antimülleriana and uterine leiomyomas.
Assuntos
Hormônio Antimülleriano/sangue , Leiomioma/sangue , Neoplasias Uterinas/sangue , Adulto , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Estradiol/sangue , Feminino , Humanos , Leiomioma/patologia , Pessoa de Meia-Idade , Progesterona/sangue , Receptores de Peptídeos/metabolismo , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Neoplasias Uterinas/patologiaRESUMO
The cytochrome P-450 1A1 (CYPA1A) gene plays an important role in the metabolization of estrogen and is therefore a candidate marker for fibroids. In a case-control study, we were unable to demonstrate any association between MSP I CYP1A1 polymorphism and the risk of leiomyoma in Brazilian women.
Assuntos
Citocromo P-450 CYP1A1/genética , Desoxirribonuclease HpaII , Leiomioma/genética , Polimorfismo de Fragmento de Restrição/fisiologia , Neoplasias Uterinas/genética , Adulto , Brasil , Estudos de Casos e Controles , Citocromo P-450 CYP1A1/fisiologia , Desoxirribonuclease HpaII/metabolismo , Estradiol/sangue , Estradiol/farmacocinética , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Leiomioma/sangue , Leiomioma/metabolismo , Taxa de Depuração Metabólica/genética , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição/genética , Fatores de Risco , Neoplasias Uterinas/sangue , Neoplasias Uterinas/metabolismoRESUMO
Gestational trophoblastic disease has been reported to be responsive to chemotherapy, with a 90% cure rate. Several factors place patients at high risk of experiencing treatment failure with single agent chemotherapy. Choriocarcinoma following term pregnancy is very rare and associated with a poor prognosis and a mortality rate of 33-40%. We present a rare case of cutaneous metastasis of choriocarcinoma to the left third digit.