Expression of epidermal growth factor and its receptor in gestational trophoblastic diseases

Objective: To determine whether epidermal growth factor (EGF) and its receptor have any possible correlation with etiology of gestational trophoblastic diseases. Methods: Avidin-biotin immunoperoxidase techniques with polyclonal antibodies against EGF, EGFR were used to examine 53 cases of GTD, including complete hydatidiform mole(16),invasive mole(20),gestational choriocarcinoma(17).Results:EGF was mainly localized on syncytiotrophoblasts (ST), and was found less on cytotrophoblasts. Cytologic localization of EGFR showed the similar results. The positive rate of EGF and EGFR were 0.625, 0.813 in hydatidiform mole, 0.405, 0.450 in invasive mole and 0.118, 0.235 in gestational choriocarcinoma. There was significant difference of EGF or EGFR among hydatidiform mole group and other groups, respectively (P<0.05). Conclusion:The cellular levels of EGF and EGFR decreased gradually in the development of GTD. It implied that the autocrine and paracrine mechanism may play an important role on the proliferation and differentiation of trophoblast cells and the disorder of the system may lead to GTD malignant transformation.

Illness Perception in Gestational Trophoblastic Disease Patients: How Mental Representations Affect Anxiety, Depression, and Infertility-Related Stress

Gestational Trophoblastic Disease encompasses a group of pregnancy-related disorders that derive from the placenta. Taking Leventhal’s Common Sense Model as a starting point, this study aims to investigate how illness perception could influence patients’ psychological adaptation to these rare diseases. Thirty-seven women completed: the Illness Perception Questionnaire-Revised, the Beck Depression Inventory Short Form, the State-Trait Anxiety Inventory, and the Fertility Problem Inventory. Results show that the perception of severe illness consequences significantly predicts the level of anxiety patients reported at the time of questionnaire completion. Furthermore, mental representations of illness present a significant association with infertility-related stress. Specifically, the belief in the efficacy of the treatment results in fewer feelings of discomfort and isolation from family and social context due to infertility-related problems. Since patients’ illness perception was found to have a specific impact on both anxiety and infertility-related stress, this variable should be considered in the planning of a clinical intervention.

The Role of Ultrasound in the Diagnosis and Management of Trophoblastic Diseases (TMD) at the University Teaching Hospital Yalgado Ouedraogo (UTH-YO) of Ouagadougou

Objective: To describe the place of ultrasound in the diagnosis and management of Gestational Trophoblastic Diseases (GTD) at the Ouagadougou UTH-YO, Ouagadougou, Burkina Faso. Materials and Patients: It was a prospective and descriptive study over a 3-year period from 1 January 2015 to 31 December 2017. It took place in the gynecology and obstetrics department of at the University Teaching Hospital Yalgado Ouedraogo (UTH-YO) of Ouagadougou. Monitoring was based on clinical examination data, ultrasound and kinetics of β-gestational chorionic hormone (GCH) levels. Results: During the study period, we recorded 34 cases of trophoblastic diseases. The average age of the patients was 35 years with extremes of 22 and 52 years. Physical examination revealed a uterus larger than gestational age in 17 patients (56.67%) of cases. Eight (26.67%) patients were asymptomatic. The initial mean β-GCH was 453,747.8 IU/l with extremes of 5903 IU/l and 1,890,000 IU/l. Ultrasound was used to evoke the diagnosis in 23 patients, that to say 76.67% of the cases. Ultrasound identified 10 complete mole cases, 20 partial mole cases. For the 3 cases of invasive mole, pelvic ultrasound revealed heterogeneous intrauterine multi-vesicular images. In a case of choriocarcinoma, ultrasound found an enlarged uterus with a poorly limited intracavitary heterogeneous fundic image. Conclusion: This short series shows the central role of ultrasound in the diagnosis and follow-up of gestational trophoblastic diseases. Indeed, the sensitivity of ultrasound is excellent in the early diagnosis of complete moles. Ultrasonography remains a good examination choice for the diagnosis of gestational trophoblastic tumors despite their great polymorphism. The place of ultrasound in prognostic evaluation and treatment monitoring deserves to be studied by more important series.

A rare cause for gestational trophoblastic neoplasia: Placental site trophoblastic tumor

Placental site trophoblastic tumor is a rare sub-group of gestational trophoblastic neoplasia. There is a wide clinical spectrum of presentation and behaviour ranging from a benign condition to an aggressive disease with a fatal outcome. We report a case of placental site trophoblastic tumor in 23-year-old women with irregular vaginal bleeding during postpartum lactation period. In addition to persistent low level β-hCG titers, ultrasound examination revealed a suspicious low-echoic area in the myometrium consistent with gestational trophoblastic disease. After histopathological examination of the specimen achieved by ultrasound-guided dilatation and curettage of the uterus, the placental site trophoblastic tumor diagnosis was made and subsequently total abdominal hysterectomy was performed. The patient had an uneventful recovery, and no recurrence was detected for 40 months in the follow-up period.

Gestational Trophoblastic Neoplasia: Clinical and Therapeutic Profile in Madagascar

Gestational trophoblastic disease (GTD) develops from abnormal cellular proliferation of trophoblasts following fertilization. This includes complete and partial hydatidiform mole (HM) and gestational trophoblastic neoplasia (GTN). The aim of this study was to report the epidemiological, clinical and therapeutic profile of gestational trophoblastic neoplasia (GTN) over period of ten years in the department of Oncology Radiotherapy at the University Hospital Joseph Ravoahangy Andrianavalona (HJRA) Antananarivo Madagascar. Medical records of women diagnosed with GTD in the department of Oncology Radiotherapy at HJRA from January 1st, 2007 to September 2017 were retrospectively reviewed. Only patients with the FIGO diagnosis GTN were included, while those with the histological diagnosis of hydatidiform mole (HM), also sometimes classified as GTD, were not included in this study. Also excluded were all cases with incomplete or missing data. Twenty four patients were included. Median age of patients at the time of diagnosis was 37 years (range 18 - 60). Most patients developed GTN following molar pregnancy (75%), had disease duration from antecedent pregnancy of less than 6 months (58.20%), and had the pre-treatment hCG level more than 10,000 IU/L (58.27%). At diagnosis, 14 patients (58.33%) had localized disease (M0). Most common metastatic sites at initial diagnosis were the liver and brain (20.83%). After a median follow-up from initial diagnosis of six months (range 1 - 24), 58.33% were lost to follow up. This represented an increase in the percentage of patients lost to follow up prior to completion of therapy, when compared with our previous results for an earlier time period. GTN in Malagasy woman displays an aggressive clinic profile. Finding ways to increase treatment compliance provides the best way to minimize recurrences of this potentially deadly disease.

Updates in the Diagnosis of Gestational Trophoblast Disease

GTD (Gestational Trophoblastic Disease) is a pathology that encompasses benign and malignant clinical forms, affects women of childbearing age, has a variable incidence and is more frequent in developing or underdeveloped countries, colliding with the economic barrier. The frequent absence of clear protocols and guidelines for the correct diagnosis of the pathology results in inadequate classification, imprecise treatment and failed post-therapeutic observation, increasing the risk of relapses, morbidity and mortality. The present study aims to point out updated national and international practice protocols of diagnosis of GTD, through an integrative review. Seven articles were selected and it was observed that the main international reference centers are agreed with the management suggested by the IFGO (International Federation of Gynecology and Obstetrics), being the conduct in the Hydatidiform Mole (HM): evacuation by suction and curettage under ultrasound guidance, followed by hCG monitoring every 1 - 2 weeks until normalized (usually one month for Partial Hydatidiform Mole six months for Complete Hydatidiform Mole and one year for Gestational Trophoblastic Neoplasia). Unfortunately, regarding the diagnosis of MH, the guidelines of some countries show the absence or difficulty of access to the karyotype test and ploid p57 or pelvic ultrasound accompanying the uterine curettage, contrary to what is proposed by the IFGO guideline. Establishing and complying with consistent guidelines can improve patient care, with early diagnosis of the pathology and its complications, reducing the rate of recurrence, morbidity and mortality, especially in less developed countries.

人绒毛膜促性腺激素持续性低水平升高误诊分析

目的分析人绒毛膜促性腺激素(hCG)持续性低水平升高误诊原因及防范措施。方法回顾性分析2022年5月—2023年12月收治的2例初诊误诊的hCG持续性低水平升高临床资料。结果1例因停经伴血hCG值升高4月余,化疗后未见血hCG值下降就诊;1例因人工流产后50 d,异常子宫出血4 d就诊。超声检查1例提示无异常,1例发现宫腔异常回声及子宫肌层低阻回声。1例初诊为妊娠滋养细胞疾病(GTD)予甲氨蝶呤联合甲酰四氢叶酸方案化疗2个周期;1例初诊为子宫动静脉瘘+妊娠物残留,予子宫动脉造影联合宫腔镜诊断性刮宫。1例化疗后未见血hCG值下降;1例造影结果阴性,宫内物病理检查未见妊娠物。2例均确诊为原发性hCG持续性低水平升高,未予特殊处理。结论hCG持续性低水平升高临床少见、表现不典型,若未行血尿hCG检查、性激素检查或未仔细分辨超声图像特征,极易与滋养细胞疾病等混淆。接诊医生应提高本病警惕性,加强对本病的认识,对有停经史、异常子宫出血者应及早行血尿hCG、超声及磁共振检查,仔细询问病史,必要时纳入性激素全套及卵巢功能检测以明确诊断。

MRI联合血β-HCG鉴别诊断妊娠滋养细胞疾病与病理结果一致性分析

目的分析MRI联合血β-绒毛膜促性腺激素(β-HCG)鉴别诊断妊娠滋养细胞疾病(GTD)与病理结果的一致性。方法回顾性分析2021年1月至2023年6月郑州市中心医院收治的89例GTD患者的临床资料,比较不同性质GTD患者MRI表现特征及血清β-HCG水平,以组织病理结果为金标准,采用受试者工作特性(ROC)曲线及卡帕(Kappa)值分析MRI联合血β-HCG检测的鉴别诊断价值及一致性。结果恶性GTD患者的血β-HCG水平为(20384.66±317.00)mU/mL,明显高于良性GTD的(840.66±257.33)mU/mL,差异有统计学意义(P<0.05);MRI联合血β-HCG鉴别诊断恶性GTD的灵敏度、阳性预测值(98.55%、100.00%)明显高于MRI(84.06%、90.00%)和血β-HCG(68.12%、40.00%),两者联合诊断的特异度、阴性预测值(100.00%、95.24%)明显高于血β-HCG(79.66%、26.67%),差异均有统计学意义(P<0.05);绘制ROC曲线显示,MRI联合血β-HCG鉴别诊断GTD的AUC为0.993,大于MRI、血β-HCG的0.870、0.541(P<0.05);MRI联合血β-HCG鉴别诊断GTD与病理结果一致性为94.38%,Kappa值为0.830(95%CI:0.623~1.036)。结论MRI联合血β-HCG水平检测与病理结果存在较高的一致性,其联合检测可显著提高GTD鉴别诊断准确性,有助于临床制定有效治疗方案。

宫颈妊娠误诊一例并文献复习

目的了解宫颈妊娠的相关临床诊治经过以减少宫颈妊娠的误诊。方法报道一例宫颈妊娠患者的诊治情况并进行分析,反思诊治经过,总结经验,以提高临床医生对血HCG极高的宫颈妊娠的防范意识。结果本例患者行经腹腔镜全子宫及双附件切除术,术后病理确诊宫颈妊娠,预后良好,未见严重并发症的发生。结论宫颈妊娠临床少见且症状不典型,与难免流产、不全流产、先兆流产、滋养细胞肿瘤等鉴别困难,加强认识、提高诊治水平,做到早发现、早诊断、早治疗,改善患者的预后。

EXPRESSION OF P53 PROTEIN AND PROLIFERATING CELL NUCLEAR ANTIGEN IN HUMAN GESTATION TROPHOBLASTIC DISEASE

To study the relationship between p53 protein, proliferating cell nuclear antigen (PCNA) expression and benign or malignant gestational trophoblastic disease (MGTD). Methods: The histotomic sections of 48 patients with gestational trophoblastic disease and 24 patients of normal chorionic villi were stained using immunohistochemistry. The monoclonal antibodies were used to determine p53 protein and PCNA. Results: The frequency of p53 and PCNA positive expression were significantly different among the chorionic villi of normal pregnancy, hydratidiform mole (HM) and MGTD. But neither p53 nor PCNA has any relation with the clinical staging or metastasis of MGTD. Conclusion: Both P53 and PCNA are valuable in diagnosis of human gestational trophoblastic disease.

Management of Gestational Trophoblast Disease: A Review Integrative National and International Guidelines

GTD (Gestational Trophoblastic Disease) is a pathology that encompasses benign and malignant clinical forms, affects women of childbearing age, has a variable incidence and is more frequent in developing or underdeveloped countries, colliding with the economic barrier. The frequent absence of clear protocols and guidelines for the correct diagnosis and treatment of the aforementioned pathology results in inadequate risk classification, imprecise treatment and failed post-therapeutic observation, increasing the risk of relapses, morbidity and mortality. The present study aims to compare the different national and international guidelines in the management of GTD, through an integrative review. Nine articles were selected and it was observed that the main international reference centers are agreed with the management suggested by the IFGO (International Federation of Gynecology and Obstetrics), being the conduct in the Hydatidiform Mole (HM): evacuation by suction and curettage under ultrasound guidance, followed by hCG monitoring every 1 - 2 weeks until normalized;in low-risk GTN (Gestational Trophoblastic Neoplasm): chemotherapy with methotrexate or actinomycin D, in high-risk: EMA/CO protocol, in ultra-high-risk EMA/PE, methotrexate with radiotherapy for brain metastases. All medical societies recommend the registration of these patients in GTD screening centers, endorse the use of the IFGO scoring system (2000) and recommend the surgical management of placental site trophoblastic or epithelioid tumors, as chemotherapy is less effective in these cases. The controversies are in the proper follow-up after the treatment of HM, use of ultrasound to evacuate the uterus, administration of anti-D immunoglobulin, time of oxytocin infusion and rescue regimens that can be used in cases of resistant or recurrent GTN. Establishing and complying with consistent guidelines can improve patient care, with early diagnosis of the pathology and its complications, reducing the rate of recurrence, morbidity and mortality, especially in less developed countries.

完全性葡萄胎与胎儿共存一例并文献复习

葡萄胎与胎儿共存(hydatidiform mole and co-existing fetus,HMCF)是产科的罕见疾病,包括完全性葡萄胎与胎儿共存(complete hydatidiform mole with co-existing fetus,CHMCF)和部分性葡萄胎与胎儿共存(partial hydatidiform mole with co-existing fetus,PHMCF)。报道1例CHMCF病例通过妊娠期连续监测甲状腺功能、人绒毛膜促性腺激素和胎儿状况妊娠至37周,剖宫产分娩一活婴。CHMCF是一种临床罕见的高风险疾病,妊娠期应联合超声、磁共振成像和染色体核型分析仔细鉴别诊断,并在有产前诊断和妇科肿瘤中心的机构严密监测妊娠、分娩及产后随访。

妊娠滋养细胞疾病组织中HIF-1α、ANG-1及p53蛋白水平变化及预测葡萄胎恶变

目的:分析妊娠滋养细胞疾病组织中缺氧诱导因子-1a(HIF-1α)、血管生成素-1(ANG-1)及p53蛋白水平变化及对葡萄胎恶变的预测效能。方法:收集2018年1月-2021年1月本院诊治的妊娠滋养细胞疾病患者88例为病例组,正常早孕流产接受刮宫治疗患者88例为对照组,比较绒毛组织中HIF-1α、ANG-1及p53蛋白水平并分析对葡萄胎恶变的预测效能。结果:病例组HIF-1α、ANG-1及p53蛋白相对表达水平均高于对照组,且在病例组中绒毛膜癌、侵袭性葡萄胎、葡萄胎绒毛组织上述指标水平有差异(均P<0.05)。3项指标联合检测诊断绒毛膜癌、侵袭性葡萄胎特异度(58.1%、54.8%)高于单独指标检测。通过受试者工作特征曲线分析,HIF-1α、ANG-1及p53诊断侵袭性葡萄胎和绒毛膜癌的曲线下面积分别为0.909、0.998,诊断临界值分别为1.88、2.91、2.61,2.89、3.77、3.30。结论:妊娠滋养细胞疾病组织中HIF-1α、ANG-1及p53蛋白水平发生异常变化,联合检测对葡萄胎恶变有一定预测价值。

双胎妊娠之一完全性葡萄胎伴肺转移1例并文献复习

葡萄胎可分为完全性葡萄胎及部分性葡萄胎。完全性葡萄胎偶发于双胎妊娠,其合并的另一胎为正常活胎。本文通过简要介绍珠海市妇幼保健院1例双胎妊娠之一为完全性葡萄胎伴肺部转移,并回顾相关文献,复习近年来妊娠合并葡萄胎的研究现状,旨在为临床工作提供参考。

TGF-β1对人早孕滋养层细胞和绒毛膜癌JAR细胞增殖的影响及其意义

目的:研究转化生长因子-β1(TGF-β1)对人早孕滋养层细胞和人绒毛膜癌JAR细胞增殖的影响,探讨TGF-β1在人妊娠滋养细胞疾病发病机制中的作用和意义。方法:分别用细胞计数法、MTT比色法研究TGF-β1对两种细胞增殖活性的影响。结果:随着TGF-β1浓度的增高,TGF-β1抑制人正常早孕滋养层细胞的增殖作用加大;在一定的浓度范围内,以浓度依赖性和时间依赖性的方式促进JAR细胞的增殖,提示TGF-β1在良性滋养细胞疾病的恶变中可能有促进作用。结论:TGF-β1具双重作用,既抑制人正常早孕滋养层细胞的增殖,又在一定浓度范围内以浓度依赖性和时间依赖性的方式促进恶性滋养细胞JAR细胞系的增殖。

血管生成素在妊娠滋养细胞疾病中表达的临床意义探讨

目的:通过检测血管生成素(ANG)在人正常早孕绒毛组织、葡萄胎及妊娠滋养细胞肿瘤中表达的差异性,探讨ANG在妊娠滋养细胞疾病(GTD)表达的意义。方法:采用免疫组化(En Vision)法检测人正常早孕绒毛组织28例、葡萄胎组织26例、妊娠滋养细胞肿瘤组织14例(其中侵蚀性葡萄胎1例、绒毛膜癌12例、胎盘部位滋养细胞肿瘤1例)中ANG蛋白的表达以及定位情况。结果:ANG蛋白在人正常早孕绒毛组织、葡萄胎及妊娠滋养细胞肿瘤组织中均有表达且主要定位于细胞质和细胞膜、少量表达于细胞核;ANG阳性表达率葡萄胎组(100.0%)高于正常早孕绒毛组(60.7%)(P<0.05)和妊娠滋养细胞肿瘤组(85.7%)(P<0.05),妊娠滋养细胞肿瘤组高于正常早孕绒毛组(P<0.05)。在妊娠滋养细胞肿瘤中,ANG阳性表达率在年龄≥40岁组(83.3%)高于年龄<40岁组(75.0%)(P<0.05);临床分期晚期组(Ⅲ、Ⅳ期)(88.9%)高于早期组(Ⅰ期、Ⅱ期)(80.0%)(P<0.05);FIGO预后评分高危组(87.5%)高于低危组(83.3%)(P<0.05)。结论:ANG在GTD组织中的表达明显高于在正常早孕绒毛组织,且在妊娠滋养细胞肿瘤晚期、高危患者表达增高,表明ANG的过表达可能参与了GTD的发生过程。

妊娠滋养细胞疾病的MRI诊断及病理对照

目的:探讨妊娠滋养细胞疾病(GTD)的MRI表现及与病理改变的相关性,旨在提高对本病的认识。方法:回顾性分析21例妊娠滋养细胞疾病患者的MRI表现、病理资料、手术所见及临床资料。结果:21例中葡萄胎9例,主要MRI表现为子宫体积增大,宫腔内有葡萄状或蜂窝状囊泡影,病变包膜完整;其中8例行增强扫描,显示囊泡无明显强化,7例囊泡间分隔较均匀强化,1例分隔强化欠均匀。侵袭性葡萄胎及绒毛膜癌各6例,MRI检查示宫体扩大,腔内蜂窝状或囊实性异常信号影,分隔杂乱;包膜不完整,侵犯肌层;3例合并病变内出血;12例宫腔内或肌层内血管增粗、增多;11例子宫周围血管增多、纡曲;其中5例行增强扫描,显示肿瘤内分隔及实性部分强化,囊性部分无明显强化,2例病变内有片状强化。结论:妊娠滋养细胞疾病的MRI表现具有一定特征性,MRI能较好地显示病变的内部结构、明确肿瘤范围,结合临床病史及实验室检查可以作出诊断,并可在早期提示病变的良恶性,从而指导临床制订治疗方案。

滋养细胞疾病15例误诊分析

目的:探讨滋养细胞疾病的正确诊断及鉴别诊断。方法:回顾分析2000年1月至2004年7月收治的将滋养细胞疾病误诊为其它疾病8例及将其它疾病误诊为滋养细胞疾病7例的临床资料。结果:滋养细胞疾病8例误诊为异位妊娠5例,不全流产2例,子宫肌瘤1例;误诊为滋养细胞疾病的7例中异位妊娠4例,早孕合并阔韧带肌瘤、动静脉瘘及不全流产各1例。结论:滋养细胞疾病的正确诊断应该结合病史,HCG监测,影像学检查,刮宫等综合考虑,对难以诊断的患者不能盲目化疗,可以通过腹腔镜或开腹手术以明确诊断。

错配修复基因启动子甲基化和蛋白表达在葡萄胎的发生及恶变中的作用

目的探讨错配修复基因hMLH1和hMSH2启动子甲基化和蛋白表达在葡萄胎的发生及恶变中的作用。方法用甲基化敏感性核酸内切酶HpaⅡ酶切-PCR法,分析正常早孕人流绒毛、部分性葡萄胎(PM)、完全性葡萄胎(CM)和侵蚀性葡萄胎(IM)hMLH1和hMSH2启动子甲基化情况;免疫组化检测hMLH1和hMSH2原位蛋白表达。结果在正常早孕绒毛、PM、CM和IM组织中,hMLH1和hMSH2均表达于细胞滋养细胞,合体滋养细胞大多表达阴性,极少数为弱阳性。正常早孕绒毛组织均未发现hMLH1和hMSH2启动子甲基化,而hMLH1和hMSH2表达全部阳性,阳性率为100%,与PM、CM组织相比,启动子甲基化和蛋白表达均存在显著性差异(P<0.05)。IM中hMLH1和hMSH2启动子甲基化发生率分别为80.0%(12/15)和73.3%(11/15),与PM、CM相比无显著性差异(P>0.05);IMhMLH1蛋白表达阳性率为54.5%(6/11),与PM、CM相比无显著性差异(P>0.05);而hMSH2蛋白表达阳性率为36.4%(4/11),明显弱于CM,两者比较有显著性差异(P=0.044)。CM和IM组织中hMSH2启动子甲基化与其蛋白表达间存在相关性(P值分别=0.001和0.039)。结论hMLH1和hMSH2的高表达对正常细胞滋养细胞基因组的稳定性起着重要的作用;hMLH1和hMSH2启动子甲基化的发生和蛋白表达的缺失参与了葡萄胎的发生。

妊娠滋养细胞疾病与“二胎”妊娠

随着"二胎"政策全面实施,瘢痕子宫、高龄产妇带来了很多妇科和产科的难题。在重视和应对产科挑战的同时,我们应该同样重视"二胎"妊娠带来的妇科问题,其中葡萄胎发病率升高,可能继发妊娠滋养细胞肿瘤,及妊娠滋养细胞肿瘤患者治疗后的二胎问题,都是目前关注的热点。本文围绕妊娠滋养细胞疾病与"二胎"妊娠的问题,阐述了年龄与妊娠滋养细胞疾病发生发展的关系,化疗对妊娠滋养细胞肿瘤患者卵巢功能的影响,化疗过程中卵巢功能的保护,及治疗后再次妊娠的时机及预后等问题。