恶性滋养细胞肿瘤的诊断

恶性滋养细胞肿瘤的诊断重庆医科大学附属一院（６３００４２）卞度宏四川省肿瘤医院（６１００４１）张国楠恶性滋养细胞肿瘤有非妊娠性和妊娠性之分，前者称原发性绒毛膜癌，本文从略。而妊娠恶性滋养细胞肿瘤系源自下一代的滋养细胞，为继发于妊娠的半异体肿瘤，较为常...     

妊娠滋养细胞肿瘤nm23H1和PCNA的表达及其临床意义

目的 观察ｎｍ２３Ｈ１表达与妊娠滋养细胞肿瘤转移及细胞地殖状态的关系，并观察化疗对滋养细胞肿瘤细胞增殖状态的影响。方法 采用免疫组化方法检测４８例妊娠滋养细胞肿瘤手术标本、１０全恶性循环葡萄胎和１０例正常早孕绒毛组织刮宫标本中ｎｍ２３Ｈ１和ＰＣＮＡ的表达。结果 正常早孕绒毛或葡萄胎的ｎｍ２３Ｈ１，表达较妊娠滋养细胞肿瘤强（Ｐ〈０．０１），妊娠滋养细胞肿瘤中侵蚀性葡萄胎较绒癌强（Ｐ，０．０５），ＷＯ     

妊娠滋养细胞疾病／肿瘤合并妊娠

滋养细胞疾病／肿瘤与妊娠同时合并在临床上较为少见或罕见，它可分为完全性葡萄胎合并妊娠，部分性葡萄胎合并妊娠．绒癌合并妊娠和胎盘部位滋养细胞肿瘤合并妊娠四种情况。     

妊娠滋养细胞肿瘤（疾病）保留生育功能的治疗

妊娠滋养细胞疾病是一系列的疾病，包括葡萄胎、侵蚀性葡萄胎（简称侵葡）、绒毛膜癌（简称绒癌）和胎盘部位滋养细胞肿瘤（简称ＰＳＴＴ）。除葡萄胎外，后三者又统称妊娠滋养细胞肿瘤。葡萄胎约有１４．５％～２０％可恶变为滋养细胞肿瘤，这类疾病大多发生在生育年龄的...     

妊娠滋养细胞肿瘤的病理

妊娠滋养细胞肿瘤的病理浙江医科大学妇产科医院（３１０００６）赵承洛妊娠滋养细胞肿瘤（ｇｅｓｔａｔｉｏｎａｌｔｒｏｐｈｏｂｌａｓｔｉｃｔｕｍｏｒ，ＧＴＴ）具有胚胎绒毛滋养细胞的一些生理特性，如向母体组织血管浸润，放逐的绒毛滋养细胞可在母体血管内游走，因...     

妊娠滋养细胞肿瘤靶向及免疫治疗进展

妊娠滋养细胞肿瘤是与妊娠相关的唯一一种可能通过化疗治愈的妇科恶性肿瘤。妊娠滋养细胞肿瘤对化疗极其敏感,但是也有部分患者出现耐药。近年来,随着基础研究的深入,免疫治疗和靶向治疗逐渐成为研究的热点,本文就免疫治疗和靶向治疗在妊娠滋养细胞肿瘤中的临床应用作一综述。     

妊娠滋养细胞肿瘤保留生育功能治疗的研究进展

妊娠滋养细胞肿瘤（gestational trophoblastic neoplasms，GTN）包括侵蚀性葡萄胎、绒毛膜癌、胎盘部位滋养细胞肿瘤和上皮样滋养细胞肿瘤。GTN多发生于育龄妇女，因此治疗的同时保留患者生育功能尤为重要。本文阐述了保留生育功能治疗GTN的方法，如全身静脉化疗或动脉插管化疗、动脉栓塞治疗、保守性手术等，并总结保留生育功能治疗后的妊娠结局研究进展。     

妊娠滋养细胞疾病表皮生长因子受体表达的研究

研究表皮生长因子受体在妊娠滋养细胞疾病中的组织定位和表达,探讨ＥＣＦＲ与妊娠滋养细胞疾病的关系。方法采用单克隆抗体ＳＰ免疫组化技术测定３１例葡萄主４２例妊娠滋养细胞肿瘤中ＥＧＦＲ的表达情况。     

妊娠滋养细胞肿瘤中cyclin D1和CDK4的表达及意义

目的：探讨细胞周期素D1(cyclindepemlent kinas，cyclin D1)和细胞周期依赖激酶4(cyclin-depemlent kINASE 4，CDK4)在妊娠滋养细胞肿瘤发生、发展中的作用。方法：采用免疫组化SP法检测cyclin D1、CDK4在妊娠滋养细胞疾病中的表达。结果：cyclin D1在葡萄胎、侵蚀性葡萄胎和绒毛膜癌组织中的阳性表达率分别为20％、72．22％和88．89％，CKD4的阳性表达率分别为16．67％、61．11％和72．22％，妊娠滋养细胞肿瘤组与葡萄胎比较，cyclin D1和CDK4的表达率明显增高，差异有统计学意义，P<O．01；在妊娠滋养细胞肿瘤中，cyclin D1和CDK4的表达成正相关，r=5．675，P=O．017；妊娠滋养细胞肿瘤Ⅰ～Ⅱ期、Ⅲ～Ⅳ期组织中，cyclin D1的阳性表达率分别为70％和93．75％，CDK4的阳性表达率分别为50％和87．5％，随肿瘤临床期别的增加，cyclin D1和CDK4的表达率逐渐升高。结论：cyclin D1和CDK4在妊娠滋养细胞疾病中过度表达，并与其发生和发展有关。     

妊娠滋养细胞肿瘤子宫病灶大出血的处理

妊娠滋养细胞肿瘤因肿瘤细胞具有亲血管性，极易因肿瘤侵袭血管而发生子宫病灶大出血。子宫病灶大出血较凶险，但保守治疗难以奏效，处理上比较棘手，其中放射介入动脉栓塞术、手术治疗为常用的两种方法。本文对妊娠滋养细胞肿瘤子宫病灶大出血的放射介入动脉栓塞术和手术治疗的应用效果、注意事项及出血处理后的治疗研究进展进行阐述。     

Characterization of antigenic components from circulating immune complexes in patients with gestational trophoblastic neoplasia

The authors have studied serial circulating immune complex (CIC) levels in 15 patients with gestational trophoblastic neoplasia (GTN) for several reasons. Gestational trophoblastic neoplasia can easily be followed from presentation to remission, and CIC changes can be compared with changes in human chorionic gonadotropin (HCG) which is a specific and quantitative marker of trophoblastic tumor load. Twelve patients with hydatidiform molar pregnancy presented with normal CIC levels (255 delta OD450 +/- 97, mean SE [standard error]) as measured by our antigen nonspecific polyethylene glycol (PEG) turbidity assay. Only after reduction in tumor load as monitored by a fall in HCG did CIC rise. In contrast, three patients with choriocarcinoma presented with significantly elevated CIC levels (513 delta OD450 +/- 147, P less than 0.05 compared to normals) which slowly declined in parallel with HCG levels following evacuation and chemotherapy. Sera at peak PEG-CIC from three patients with molar pregnancy or choriocarcinoma were precipitated with 3.75% polyethylene glycol to concentrate circulating immune complexes. Circulating immune complex levels were fractionated on Sephadex G-200 in an acid buffer (pH = 2.8). An identifiable antigenic component of the CIC in both diseases was found to be paternal HLA antigen. This was demonstrated by the ability of the latest eluting CIC fraction to inhibit paternal lymphocyte lysis using anti-HLA antisera against the husband's HLA tissue type. In each case, this fraction contained no immunoglobulin or beta-2 microglobulin and was antigenically crossreactive with only one of the husband's HLA haplotypes. The authors believe the PEG-CIC assay has allowed them to define the kinetics of host humoral response in GTN, and has provided a method for recovering immunogenic tumor-associated antigens from these complexes which may apply to other solid tumors.     

Circulating immune complex levels in patients with gestational trophoblastic neoplasia

The clinical course, human chorionic gonadotropin (HCG) levels, and serial circulating immune complex (CIC) levels in 21 patients with gestational trophoblastic neoplasia (GTN) were correlated for the evaluation of the relationship between CIC levels and trophoblastic tumor burden. CIC levels were normal in 18 of 21 patients at the time of presentation, and 2 of 3 patients who presented with elevated CIC levels had significant comorbid disease (toxemia and hepatitis). Nine patients were followed into gonadotropin remission, and all 9 developed an increase in CIC levels at the time of remission. It was concluded that CIC, at least as measured by two antigen-nonspecific techniques, is generally not elevated at initial presentation in the patient with GTN; this lack of an elevation is probably due to marked tumor antigen excess. Thus the in vivo importance of CIC as a "blocker" of host antitumor response at this stage is doubtful. After effective treatment as HCG levels return to normal, the demonstrated elevation in serial levels of CIC may reflect a return of adequate host immune response at a time of minimal tumor burden.     

化疗联合手术治疗耐药性妊娠滋养细胞肿瘤的临床分析

目的 探究化疗联合手术治疗耐药性妊娠滋养细胞肿瘤(Gestational trophoblastic neoplasia,GTN)患者的临床效果。方法 选择耐药的高危型GTN患者76例,随机分为对照组和研究组,各38例;对照组使用足叶乙甙+甲氨蝶呤+放线菌素D/足叶乙甙,顺铂(etoposide,methotrexate,and actinomycin-D/etoposide and cisplatin,EMA/EP)方案化疗,研究组使用化疗联合手术治疗的方法治疗;比较两组的治疗效果、预后、外周血林白细胞亚群以及不良反应发生情况。结果 治疗6个月后研究组的客观缓解率(Objective response rate,ORR)高于对照组,差异具有统计学意义(P=0.024);研究组的耐药率和复发率低于对照组(P＜0.05);治疗前两组血清人绒毛膜促性腺激素(Human chorionic gonadotropin,HCG)差异无统计学意义,治疗后两组HCG水平均降低(P＜0.001),治疗后6个月、12个月和末次随访研究组的血清HCG水平低于对照组(P＜0.001);治疗前两组外周血T细胞亚群水平差异无统计学意义,而治疗6个月后均有不同程度的改善;研究组的CD3⁺、CD4⁺和CD4⁺/CD8⁺T细胞高于对照组(P＜0.001);研究组的中性粒细胞减少、血红蛋白降低、恶心呕吐、脱发的发生率则低于对照组(P＜0.05)。结论 对于一线耐药的高危GTN患者,化疗联合手术治疗具有更好的治疗效果,并可有效改善机体免疫水平,降低不良反应的发生。     

Gestational trophoblastic neoplasia

As a result of modern diagnostic and therapeutic techniques, nearly 100 percent of patients with GTN can be cured of a disease thay only a few years ago had a high death rate. To achieve this, skillful mixing of chemotherapy, surgery, and irradiation, as well as supportive therapy, are necessary. Understanding and utilizing the HCG assay to monitor disease status is vital. With this approach, essentially all of these patients should survive, many to have successful future pregnancies.     

Identification of material with paternal HLA antigen immunoreactivity from purported circulating immune complexes in patients with gestational trophoblastic neoplasia

Circulating immune complex(es) (CIC) have been shown to rise progressively only when patients with hydatidiform molar pregnancy enter gonadotropin-documented remission. The CIC in 3 patients with gestational trophoblastic neoplasia (GTN)--1 with hydatidiform mole and 2 with choriocarcinoma--were characterized. Their clinical course was monitored by serial antigen-nonspecific polyethylene glycol (PEG) 6000-CIC assay and simultaneous human chorionic gonadotropin (HCG) assay from presentation until sustained gonadotropin-documented remission. As serial HCG progressively decreased to normal following surgical or chemotherapeutic reduction in tumor burden, PEG-CIC concurrently rose. Serum obtained at or near peak PEG-CIC levels was precipitated by 3.75% PEG 6000 and fractionated by column chromatography on Sephadex G-200 (exclusion limit, greater than 600,000 mol wt) in glycine-HCl and 1 M NaCl buffer at pH 2.8. None of the 5 elution fractions obtained from the 3 patients contained HCG or anti-HCG activity. However, in the hydatidiform molar patient, fractions 1 through 3 (mol wt greater than 67,000--and containing immunoglobulin) were shown to competitively inhibit complement-dependent antibody lysis on 1 of 4 paternal HLA haplotype (AW32) targets. In 2 of the 3 patients studied, low-molecular-weight fractions (not containing immunoglobulin) significantly inhibited reference anti-HLA binding of antisera directed against only 1 of 4 paternal HLA haplotypes. The immunospecificity of this inhibition was confirmed by criss-cross control assays in which elution fractions obtained from both of these patients were tested for inhibition of lymphocytolysis of both sets of paternal lymphocytes. None of these fractions were immunoreactive to maternal HLA haplotypes. Further analysis of serum from the hydatidiform molar patient revealed that no free complement-fixing antibody against paternal antigens could be found by conventional screening assays in unfractionated patient sera. Three of 4 paternal HLA antigens or non-complement-fixing anti-HLA immunoglobulin was detected in unfractionated pretreatment, treatment, and remission sera of the hydatidiform molar patient. Only in this patient's remission sera was unbound AW32 antigen or non-complement-fixing anti-AW32 antibody detected. These data demonstrate the successful characterization of at least 1 specific antigen fractionated from a tumor-associated immune complex. The implication that some patients with GTN may recognize and react to immunogenic paternal HLA antigens as part of their successful response to therapy for trophoblastic tumor is discussed.     

Human Chorionic Gonadotropin (hCG) Regression Curve for Predicting Response to EMA/CO (Etoposide,Methotrexate, Actinomycin D,Cyclophosphamide and Vincristine) Regimen in Gestational Trophoblastic Neoplasia

Background: An hCG regression curve has been used to predict the natural history and response tochemotherapy in gestational trophoblastic disease. We constructed hCG regression curves in high-risk gestationaltrophoblastic neoplasia (GTN) treated with EMA/CO and identified an optimal hCG level to detect EMA/COresistance in GTN. Materials and Methods: Eighty-one women with GTN treated with EMA/CO were classifiedas primary high-risk GTN (n = 65) and single agent-resistance GTN (n = 16). The hCG levels prior to each courseof chemotherapy were plotted in the 10th, 50th, and 90th percentiles to construct the hCG regression curves.Diagnostic performance was evaluated for an optimal cut-off value. Results: The median hCG levels were 264,482mIU/mL mIU/mL and 495.5 mIU/mL mIU/mL for primary high-risk GTN and single agent-resistance GTN,respectively. The 50th percentile of the hCG level in primary high-risk GTN and single agent-resistance turnedto normal before the 4th and the 2nd course of chemotherapy, respectively. The 90th percentile of the hCG levelin primary high-risk GTN and single agent-resistance turned to normal before the 9th and the 2nd course ofchemotherapy, respectively. The hCG level of ≥ 118.6 mIU/mL mIU/mL at the 5thcourse of EMA/CO predictedthe EMA/CO resistance in primary high-risk GTN patients with a sensitivity of 85.7% and a specificity of 100%.Conclusion: EMA/CO resistance in primary high-risk GTN can be predicted by using an hCG regression curvein combination with the cut-off value of 118.6 mIU/mL at the 5thcourse of chemotherapy.     

Gestational trophoblastic neoplasia

Gestational trophoblastic neoplasia (GTN) is one of the most curable malignancies because of the intrinsic sensitivity of the tumor to certain antineoplastic agents, effective sensitive assays for human chorionic gonadotropin (hCG), and identification of high‐risk factors that permit individualized treatment. Chemotherapy is the main modality of treatment in patients with GTN. The cure rate in patients with low‐risk GTN is 100%, and is estimated to exceed 80% in patients with high‐risk GTN. Management of GTN is based on staging (anatomical involvement staging) and scoring. Patients with persistent GTN and stage I or score ≤ 6 (low risk) should be managed with single agent chemotherapy (methotraxate or actinomycin), but patients with stage IV or score ≥ 7 (high risk) need combination chemotherapy. Gestational trophoblastic neoplasia is radiosensitive, because radiation has hemostatic and tumorocidal effect on GTN. Therefore, radiotherapy can be used in treatment of some patients with brain hepatic metastasis or in patients where chemotherapy is not possible due to medical problems. Surgery can be used in patients who are resistant to chemotherapy or in hemorrhagic cases. Surgical resection of the tumor is the main form of therapy for placental site trophoblastic tumor. This surgery consists of a hysterectomy for the majority of patients as the disease is confined to the uterus.     

Surgical management of chemotherapy-resistant gestational trophoblastic neoplasia

Gestational trophoblastic neoplasia (GTN) are a broad spectrum of placental lesions. Chemotherapy is the primary treatment for GTN and the vast majority of women with GTN are cured with their initial chemotherapy treatment. However, some patients become chemotherapy-resistant and fail to achieve a complete remission following initial chemotherapy and need salvage chemotherapy. A small minority of patients are still unresponsive to salvage multidrug chemotherapy. Currently, adjuvant surgical procedures could be excellent adjuncts to salvage chemotherapy in removing known foci of chemotherapy-resistant disease in selected patients with persistent GTN. This article will review the surgical management of chemotherapy-resistant GTN, focusing on the relevant indication of surgery, factors affecting efficacy and the use of surgical procedures in selected patients.     

Advances in immunotherapy and molecular targeted therapy of gestational trophoblastic tumor: current practice and future perspectives

Gestational trophoblastic neoplasia (GTN) is a rare pregnancy-related gynecological malignancy caused by abnormal proliferation of placental trophoblastic cells. It can invade the uterine muscle layer and metastasize early, more common in women of childbearing age. GTN is invasive and can destroy surrounding tissues and blood vessels, causing massive bleeding in uterus and metastatic sites (such as lung, liver, brain, etc.) through blood transfer. Chemotherapy is the main treatment for GTN, and the disease is extremely sensitive to chemotherapy and can be cured by chemotherapy. However, in clinical practice, a large number of patients have failed chemotherapy or even multiple treatments due to drug resistance, recurrence or metastasis of special sites. Therefore, how to individually select the initial chemotherapy regimen and reduce the occurrence of drug resistance is the key to the treatment of high-risk GTN. With the remarkable efficacy of immunotherapy in endometrial cancer, cervical cancer and other diseases, the research on GTN has been further deepened. Therefore, this review discusses the mechanism, methods and efficacy of GTN immunotherapy and molecular targeted therapy, in order to provide new ideas for the diagnosis and treatment of GTN.