Gestational trophoblastic disease: pictorial review

Ultrasound is the modality of choice for evaluating normal or abnormal first trimester pregnancy. Sonography can usually provide a specific diagnosis in abnormal first trimester bleeding. When the sonographic appearance is correlated with the clinical presentation, accurate diagnosis is possible in most cases of gestational trophoblastic disease (GTD). Partial or complete hydatidiform moles can be diagnosed in early gestation. However certain cases will be missed if the curettage material is not sent for pathologic examination. Sometimes molar pregnancies have very unusual sonographic appearances. Sonography and Doppler imaging are helpful in diagnosing gestational trophoblastic disease, in determining whether invasive disease is present, in detecting recurrent disease, and in following the effectiveness of chemotherapy. This pictorial essay describes the pathogenesis, epidemiology, and sonographic spectrum of gestational trophoblastic disease.     

晚期滋养细胞肿瘤转移灶声像图特征

目的探讨晚期滋养细胞肿瘤转移灶的彩色多普勒声像图特征。方法回顾性分析6例滋养细胞肿瘤患者临床、血清β-hCG检测结果及其转移灶的彩色多普勒与频谱多普勒超声声像图特征。结果6例中1例绒毛膜癌（继发于流产后）彩色多普勒超声见结肠转移灶：5例侵蚀性葡萄胎（葡萄胎清除术后1-3个月发生）彩色多普勒超声检查除子宫肌壁病变外盆侧壁网状转移灶2例、腹腔转移灶1例、右肾转移灶1例,结肠转移灶1例。绒毛膜癌和侵蚀性葡萄胎子宫肌壁病变及转移灶的声像图特征雷同。彩色多普勒显示血流丰富,五彩缤纷状．多普勒流速曲线呈高流速低阻力型,阻力指数范围0．42±0．04。6例中1例绒毛膜癌结肠转移灶手术切除。其余均化疗治愈。结论彩色多普勒超声检查能即时发现晚期滋养细胞肿瘤转移灶。     

水泡状胎块中p57KIP2的表达及其意义

【目的】分析水泡状胎块中p57KIP2的表达情况,探讨其在水泡状胎块诊断及鉴别诊断中的作用和价值。【方法】采用免疫组化方法检测p57KIP2在39例完全性水泡状胎块（CHM）、33例部分性水泡状胎块（PHM）中的表达,同时选取10例正常绒毛组织作为对照组。【结果】p57KIP2在CHM组中的表达明显低于对照组和PHM组,p57KIP2在CHM组和PHM组中的表达具有显著差异（P〈0．01）。【结论】p57KIP2可以作为CHM、PHM鉴别诊断的重要参考指标。     

完全性葡萄胎与部分性葡萄胎P57KIP2表达分析

目的：检测P57KIP2在完全性葡萄胎（CHM）和部分性葡萄胎（PHM）中的表达差异。方法：对比分析33例CHM和32例PHM中P57KIP2蛋白免疫组化阳性表达率。结果：P57KIP2在CHM中表达阳性比例为0（0/33）,在PHM中,P57KIP2阳性表达比例为84.4%（27/32）,CHM与PHM的P57KIP2阳性表达率差异有统计学意义（P〈0.01）。结论：P57KIP2免疫组化染色能够帮助鉴别诊断CHM和PHM,提高诊断准确率。     

妊娠滋养细胞疾病误诊为异位妊娠三例临床分析及文献复习

目的探讨误诊为异位妊娠的妊娠滋养细胞疾病(gestational trophoblastic disease, GTD)患者的临床特点、诊治方法、误诊原因及防范措施。方法回顾性分析曾诊断异位妊娠、经术后病理检查确诊的GTD 3例临床资料。结果本组2例因急腹症就诊,经常规查体、超声及血人绒毛膜促性腺激素(HCG)和尿妊娠试验初诊为异位妊娠,经手术后病理检查确诊为输卵管绒毛膜癌和输卵管侵蚀性葡萄胎各1例;1例因下腹痛、自测尿妊娠试验阳性、突然晕倒诊断为异位妊娠,行左侧输卵管切除术后出现恶心呕吐、盆腔积血、血压升高,取手术标本病理会诊修正诊断为输卵管侵蚀性葡萄胎。3例确诊后经标准联合化疗治愈。结论特殊部位的GTD早期临床表现不典型,类似异位妊娠时易误诊,通过手术获取病理组织送检,重视监测血HCG变化,可避免延误诊治。     

彩色多普勒超声诊断滋养细胞肿瘤盆腹腔转移灶

目的探讨滋养细胞肿瘤盆腹腔转移灶的彩色多普勒超声特征。方法对13例滋养细胞肿瘤患者（绒毛膜癌4例，侵蚀性葡萄胎9例）盆腹腔转移灶的彩色多普勒及频谱多普勒超声特征及其临床血清β-hCG检测情况进行回顾性分析。结果13冽滋养细胞肿瘤中4冽绒毛膜癌彩色多普勒超声显示盆腹腔转移灶（2例宫旁转移灶、1例结肠壁转移灶、1例宫旁血窦），其中3例伴血清β-hCG升高；9例葡萄胎清除术后1～3个月发生侵蚀性葡萄胎，彩色多普勒超声均显示子宫肌壁病变及盆腹腔转移灶（宫旁血窦3例、盆侧壁网状转移2例，实性病灶中宫旁转移1例、腹腔转移1例、右肾转移1例，结肠壁转移1例），9例均伴血清β-hCG升高。13例中绒毛膜癌或侵蚀性葡萄胎患者的盆腹腔转移灶与其子宫或卵巢病灶的声像图表现极其相似，以网状结构（3例）、血窦（4例）及实性转移灶（盆腹腔转移灶6例）为特征；彩色多普勒超声显示血流丰富，频谱阻力指数范围0．34±0．07，与侵蚀子宫肌壁病变一样呈高速低阻血流。12例盆腹腔转移灶经手术或化疗取得效果后均消失，1例侵蚀性葡萄胎化疗后右肾转移灶未完全消退。结论彩色多普勒超声检查对发现子宫以外的滋养细胞肿瘤盆、腹腔转移灶有重要作用。     

良性葡萄胎恶变时间的探讨

回顾１９６３～１９９２年我院１３２例末次妊娠为葡萄胎且经病理确诊的恶性滋养细胞肿瘤病例，并探讨葡萄胎恶变成恶性葡萄胎（恶葡）或绒毛膜上皮细胞癌（绒癌）的时间相关性。结果，距葡萄胎妊娠结束时间在６月以内、６～１２月、１２月以上确诊的绒癌分别占同期病例的９／８０、１４／１７、３４／３５，提示绒癌发生与距葡萄胎妊娠结束时间呈正相关。我们认为，在未获得病理证实的情况下，对于葡萄胎排出后６月之内发病的恶性滋养细胞肿瘤，临床应诊断为恶葡，６月以上者则应诊为绒癌。     

The accuracy of first trimester ultrasound in the diagnosis of hydatidiform mole.

OBJECTIVE: Previous studies have examined ultrasound findings in histopathologically confirmed cases of hydatidiform mole. The aim of this study was to assess the first-trimester ultrasonographic findings in all women suspected of having hydatidiform mole on ultrasound and those subsequently diagnosed with hydatidiform mole after histological examination of removed products of conception after surgical evacuation of the uterus. The aim was to obtain a true sensitivity and positive predictive value for ultrasound in the diagnosis of hydatidiform mole. METHODS: A retrospective analysis was performed of all cases of sonographically suspected hydatidiform mole and histologically proven hydatidiform mole presenting to the Early Pregnancy Unit of an inner city hospital over a 4-year period. The sensitivity and positive predictive value (PPV) of ultrasound in the detection of histologically proven hydatidiform mole was calculated. RESULTS: The study group consisted of 90 women; 56 were suspected of having hydatidiform mole on ultrasound, and of these 27 (48%) had hydatidiform mole confirmed after histopathological examination of the products of conception, while no changes suggestive of hydatidiform mole were present in the other 29 cases. Overall, 61 women had hydatidiform mole confirmed on histology-41 (67%) partial hydatidiform moles (PHM) and 20 (33%) complete hydatidiform moles (CHM). The ultrasound findings in the 34 cases not suspected of hydatidiform mole were an empty sac in 8/34 (24%) women and a delayed miscarriage in the other 26/34 (76%). The overall sensitivity and positive predictive value for the ultrasound diagnosis of hydatidiform mole was 44% and 48%, respectively. For PHMs the respective values were 20% and 22% and for CHMs they were 95% and 40%. CONCLUSION: Ultrasonography is more reliable for diagnosing CHMs than for PHMs. Overall, the sensitivity of ultrasound for accurately predicting hydatidiform mole is 44%, and one in two women with an abnormal scan will have the disease confirmed on histology.     

Clinicopathologic profile of gestational trophoblastic disease

Much debate exists on factors predicting the development of persistent gestational trophoblastic disease (pGTD). Diagnosis is still limited by following persistently elevated or rising postevacutation beta-human chorionic gonadotropin (beta-hCG) titers. The aim of the present work was to evaluate the hypothesis that the presence of c-erbB-2 oncogene amplification and expression, in combination with parameters such as DNA-content and karyotype of the sex chromosomes, confer an increased risk of developing pGTD. Clinicopathological characteristics were evaluated in 36 cases of gestational trophoblastic diseases (GTD) and analyzed for c-erbB-2 amplification and protein p185 expression using differential polymerase chain reaction (DPCR) and immunohistochemical (IHC) techniques. The DNA-content was determined by image analysis on Feulgen stained nuclear cell preparations and karyotyping for XY chromosomes was performed by fluorescence in situ hybridization (FISH). The data was correlated with histopathological characteristics of GTD. Seventy-five percent (n = 27) of the examined cases showed spontaneous regression after evacuation, including 2 patients who received additional chemotherapy. Twenty-five percent (n = 9) resulted in a persistent or metastatic disease. The median time between antecedent pregnancy and GTD was 45.4 months. Complete remission was achieved in all patients with pGTD after administration of chemotherapeutic agents or adjuvant surgical procedures. Cases with cerbB-2 amplification and expression in combination with DNA hyperploidy showed higher proliferation and more aggressive behavior (2 complete hydatidiform moles with lung and liver metastases, 2 invasive moles and 1 choriocarcinoma). XY karyotype was evident in the choriocarcinoma and in 2 complete hydatidiform moles with advanced stage and DNA hyperploidy. From these results we conclude that c-erbB-2 amplification and/or protein expression in combination with DNA-content show a significant correlation with the proliferative and aggressive potential of GTD, suggesting their combined use as a possible marker for pGTD.     

P57、P63和Ki-67在水肿性绒毛中的鉴别诊断意义

目的探讨P57、P63和Ki-67在水肿性绒毛中的表达及其意义。方法利用免疫组织化学技术检测23例部分性水泡状胎块（partialhydatidiformmoles,PHM）、20例完全性水泡状胎块（completehydatidiformmoles,CHM）及13例早期水肿性流产的活检组织进行检查。结果P57在完全性水泡状胎块中不表达（19／20）或仅微弱表达（1／20）;相反,在所有的部分性水泡状胎块中,细胞滋养层细胞及绒毛间质细胞均表达P57（23／23）,且13例呈中等至强阳性表达;在大部分水肿性流产中,P57均表达（11／13）。P57在CHM与PHM、CHM与HA之间的表达差异均有统计学意义（P〈0．01）。Ki-67在水泡状胎块中的表达明显高于水肿性流产（P〈0．05）。无论是阳性细胞数量还是阳性程度,P63在三种病变中的表达均无明显差异。结论P57和Ki-67在水肿性绒毛中的表达与其临床分型显著相关,运用免疫组织化学染色的方法,联合检测P57和Kb67对鉴别不同类型的水肿性绒毛具有临床意义。P63在水肿性绒毛中的作用尚待进一步研究。     

彩色多普勒血流显像在滋养细胞瘤中的临床应用

采用彩色多普勒血流显像（ＣＤＦＩ）技术对２５例正常人和５０例滋养细胞肿瘤患者的子宫血流循环情况进行观察，患者中良性组（葡萄胎）２０例，恶性组３０例（侵蚀性１８例；绒癌１２例）。结果显示：１．良恶性组的子宫动脉ＲＩ值较正常人为低，显示了子宫循环低阻的特点；２．恶性组３０例中有２７例（９０％）见子宫肌层内呈灶状分布的五彩血流丰富区，其内ＲＩ值全部＜０．４，而正常人及良性组肌层内未见血流显示；３．动态观察，化疗有效可见肌层内局灶性血流丰富区范围渐缩小，直至消失。据此认为：利用ＣＤＦＩ来鉴别良恶性滋养细胞肿瘤及观察化疗的效果是一个很有价值的方法。     

护理干预对减轻侵蚀性葡萄胎化疗病人不良反应的影响

[目的]探讨护理干预预防和减轻侵蚀性葡萄胎病人化疗时的不良反应。[方法]将2006年10月—2007年11月80例侵蚀性葡萄胎病人随机分为对照组和干预组,对照组给予常规护理,干预组在常规护理的基础上进行相关疾病的护理干预。[结果]干预组病人化疗后发生恶心、呕吐的病人明显减少,焦虑程度明显减轻,两组比较差异有统计学意义(P<0.05)。[结论]护理干预可以减轻侵蚀性葡萄胎化疗时病人的焦虑情绪,减轻恶心、呕吐的症状,提高病人的生活质量。     

护理干预对减轻侵蚀性葡萄胎化疗病人不良反应的影响

[目的]探讨护理干预预防和减轻侵蚀性葡萄胎病人化疗时的不良反应。[方法]将2006年10月-2007年11月80例侵蚀性葡萄胎病人随机分为对照组和干预组,对照组给予常规护理,干预组在常规护理的基础上进行相关疾病的护理干预。[结果]干预组病人化疗后发生恶心、呕吐的病人明显减少,焦虑程度明显减轻,两组比较差异有统计学意义（P〈0．05）。[结论]护理干预可以减轻侵蚀性葡萄胎化疗时病人的焦虑情绪,减轻恶心、呕吐的症状,提高病人的生活质量。     

Trophoblastic disease with coexistent fetus: a sonographic and clinical spectrum.

The sonographic and clinical spectrum of coexistent live fetus and trophoblastic disease is illustrated and discussed. Two patients with a single placenta with trophoblastic change and one patient with two placentas, one normal and one with a hydatidiform mole, are described. The clinical and sonographic abnormalities in all three patients were characteristic. In the two patients with single placenta, the histologic findings were minimal. The clinical and sonographic presentations of coexistent mole and fetus are described and etiology is discussed. The implication of the lack of histologic confirmation of hydatidiform mole suggests a spectrum of findings in trophoblastic disease.     

Promoter hypermethylation of multiple genes in hydatidiform mole and choriocarcinoma

The methylation status of genes in hydatidiform mole and choriocarcinoma and its significance is relatively unexplored. We investigated the methylation status of the promoter regions of six genes, p16, HIC-1, TIMP3, GSTP1, death-associated protein kinase (DAPK), and E-cadherin in 54 hydatidiform moles, five choriocarcinomas, and 10 first trimester placenta by methylation-specific polymerase chain reaction (PCR). Immunohistochemical expression of p16, TIMP3, and E-cadherin, and quantitative real-time RT-PCR of p16 was also performed. Among the six genes examined, the promoter region of four genes (E-cadherin, HIC-1, p16, TIMP3) in choriocarcinoma and three genes (E-cadherin, HIC-1, p16) in hydatidiform mole exhibited aberrant methylation whereas none was hypermethylated in normal placenta. There was a significant correlation between methylation and reduced expression of p16, E-cadherin, and TIMP3 (P < 0.001). Fifteen of the 54 patients with hydatidiform mole developed gestational trophoblastic neoplasia requiring chemotherapy. Promoter hypermethylation of p16 alone, or combined with E-cadherin, was significantly correlated to such development (P = 0.001, 0.0005, respectively). Hypermethylation of multiple genes, especially p16, might be related to the subsequent development of gestational trophoblastic neoplasia.     

基质金属蛋白酶及其组织抑制剂与滋养细胞侵袭性生长关系的研究

目的了解基质金属蛋白酶（MMPs）和组织抑制剂（TIMPs）在滋养细胞中的定位及其在不同滋养细胞病变中的表达和相互调节作用.方法采用免疫组化方法检测MMP-2、MMP-9和TMP-1、TIMP-2在绒毛膜癌、侵袭性水泡状胎块、水泡状胎块、胎盘植入和超常反应胎盘部位等病变以及胎盘着床部位中的表达.结果MMP-2、9和TIMP-1、2主要在中间滋养细胞和合体滋养细胞表达.滋养细胞在胎盘着床部位仅表达MMP-2;超常反应胎盘部位和胎盘植入不但表达MMP-2,而且多数病例MMP-9（＋）,但阳性强度弱,TIMP-1和TIMP-2（-）;水泡状胎块较强表达MMP-2,伴持续性滋养细胞疾病MMP-9和TIMP-1、2（＋）;侵袭性水泡状胎块和绒毛膜癌MMP-2和MMP-9表达明显增强,TIMP-1和TIMP-2多数（＋）.结论在病理性妊娠中MMP-9活性增强可导致滋养细胞发生过度浸润.MMP-9的过度表达和TIMP-1、2的轻微增加,可能共同增强了肿瘤细胞的侵袭能力.     

中医食疗对侵蚀性葡萄胎化疗患者的影响

目的 探讨中医食疗对侵蚀性葡萄胎化疗患者的影响.方法 对侵蚀性葡萄胎行化疗患者80例,按住院号码的单双号随机分为干预组和对照组各40例,对照组接受常规的评估、健康教育及饮食指导,干预组在对照组基础上给予中医食疗,观察两组患者化疗不同时间血象及所出现化疗不良反应的情况.结果 干预组与对照组的白细胞、中性粒细胞比例、红细胞计数、血红蛋白、红细胞压积、血小板计数在化疗前1～2 d比较差异无统计学意义(P＞0.05),但在化疗结束第1周及第2周两组患者比较,干预组各血象指标明显比对照组好,差异有统计学意义(P＜0.05);干预组化疗出现的恶心、呕吐、口腔黏膜炎、腹泻、腹痛不良反应较对照组明显减少,差异有统计学意义(P＜0.05).结论 中医食疗应用于侵蚀性葡萄胎化疗患者能显著提高其外周血象恢复,并减少化疗所致不良反应的发生.     

The diagnostic implications of routine ultrasound examination in histologically confirmed early molar pregnancies.

OBJECTIVE: Early ultrasound examination is being used increasingly in the diagnosis of molar pregnancy. The aim of this study was to examine the diagnostic implications of routine ultrasound examination for histologically confirmed molar pregnancies. METHODS: This was a retrospective review of sonographic and histological findings in a series of consecutive cases referred to the National Trophoblastic Disease Surveillance Centre with suspected molar pregnancies. In 194 cases referred to the center over a 6-month period in whom results of a preceding ultrasound examination were documented, review of ultrasound findings and final histological diagnosis was carried out. RESULTS: There were 155 cases with a reviewed histological diagnosis of complete or partial hydatidiform mole. In 131 (67%) cases, the sonographic diagnosis was that of a missed miscarriage/anembryonic pregnancy with no documented suspicion of molar pregnancy, referral being on the basis of histological examination of products of conception. In 63 cases, ultrasound examination suggested molar pregnancy; in 53 (84%) of these, the diagnosis of molar pregnancy was correct. Overall, 37 of 64 (58%) complete moles had sonographic evidence of molar pregnancy compared to 16 of 91 (17%) partial moles. Of 155 histologically confirmed complete or partial hydatidiform moles, only 53 (34%) were suspected as molar sonographically. CONCLUSION: The majority of cases of molar pregnancy now present as missed miscarriage/anembryonic pregnancy sonographically, highlighting the importance of histological examination to diagnose gestational trophoblastic disease.     

恶性滋养细胞肿瘤的彩色多普勒血流图分型及其临床意义

应用彩色多普勒超声对30例恶性滋养细胞肿瘤的血管形态学改变进行了观察及分型，对其峰值血流速度及阻力指数进行了测定，定量测量血β-HCG水平监测化疗反应，23例葡萄股清宫术后恢复正常患者作为对照组。结果表明：①滋养细胞肿瘤血流图分为三型：弥漫型、血窦型、及实质型；②11例获病理诊断，包括1例弥漫型及5例血窦型结果为恶性葡萄胎，4例实质型，3例为绒毛膜癌，1例为化疗后变性坏死物；③不同类型血流阁与血β-HCG、子宫血流动力学改变及对化疗的反应相关性好。     

经阴道彩色多普勒超声对葡萄胎的诊断探讨

目的探讨经阴道彩色多普勒超声对葡萄胎的诊断价值。方法对本院近3年来37例患者经清宫和病理证实为葡萄胎的二维超声图像及彩色多普勒超声进行回顾性分析。结果37例患者中经阴道彩色多普勒超声诊断32例,准确率87%,误诊5例,误诊率13%。结论经阴道彩色多普勒超声诊断葡萄胎具有重要的临床价值。