Formalised consensus of the European Organisation for Treatment of Trophoblastic Diseases on management of gestational trophoblastic diseases

Gestational trophoblastic disease (GTD) is a spectrum of cellular proliferations arising from trophoblast. Their invasive and metastatic potential sometimes requires chemotherapy and/or surgery. Current management is generally associated with favourable prognosis. Therefore, treatments must be chosen according to the desire for further childbearing of each patient. The European Organisation for Treatment of Trophoblastic Diseases (EOTTD) is dedicated to optimise diagnosis, treatment, follow-up and research in GTD by bringing together knowledge of clinicians and researchers from 29 countries working in the field of GTD in Europe. This study assessed the level of agreement among an expert panel of the EOTTD in order to rationalise the management of patients in Europe. The RAND/UCLA Appropriateness Method was used to combine the best available scientific evidence with the collective judgment of experts to yield a statement regarding the appropriateness of performing a procedure at the level of patient-specific symptoms, medical history and test results. There was an agreement for 54 statements while the experts showed a disagreement for two statements. As there is little evidence from randomised trials on which to base recommendations about management of GTD, many of these recommendations are based on expert opinion derived from changes in management fact that have improved outcomes from nearly 100% fatality to nearly 100% cure rates. However, a large agreement among experts is invaluable to the individual clinician who is struggling to decide whether a fertility-sparing treatment of hydatidiform mole or a low-risk GTN can be chosen and how it must be conducted.     

Immunohistochemical analysis of c-erbB-2, Bcl-2, p53, p21WAF1/Cip1, p63 and Ki-67 expression in hydatidiform moles

Hydatidiform moles (HM) are characterized by an abnormal proliferating trophoblast with a potential for a malignant transformation. Similar to other human tumors, trophoblastic pathogenesis is likely a multistep process involving several molecular and genetic alterations. The study was performed to investigate the expression patterns of c-erbB-2 and Bcl-2 oncoproteins, p53, p21^WAF1/CIP1 and p63 tumor suppressor proteins and Ki-67 cell proliferation marker in HM.We conducted a retrospective study of 220 gestational products, including 39 hydropic abortions (HA), 41 partial HM (PHM) and 140 complete HM (CHM). The expression of c-erbB-2, Bcl-2, p53, p21^WAF1/CIP1, p63 and Ki-67 was investigated by immunohistochemistry on archival tissues. c-erbB-2 expression was observed in three PHM and 10 CHM. Bcl-2 immunostaining was significantly higher in PHM (61%) and CHM (70.7%) compared with HA (7.7%, p?=? 0.001 and p?<? 0.0001, respectively). p53 expression was stronger in CHM (73.6%) compared with PHM (24.4%, p < 0.0001) and HA (12.8%, p < 0.0001). p21^WAF1/CIP1 staining was observed as well in molar and non-molar gestations (p?>? 0.05). p63 immunoexpression was significantly described in CHM (85.7%) and PHM (78%) compared with HA (10.2%, p < 0.0001 and p = 0.0001, respectively). Ki-67 was significantly expressed in CHM (72.1%) compared with HA (46.2%, p = 0.005).Altered expression of Bcl-2, p53, p63 and Ki-67 reflects the HM pathological development. Immunohistochemical analysis is beneficial to recognize the HM molecular and pathogenic mechanisms. Furthermore, it could serve as a useful adjunct to conventional methods for refining HM diagnosis.     

Sonographic and Doppler imaging in the diagnosis and treatment of gestational trophoblastic disease: a 12-year experience.

OBJECTIVE: To evaluate the clinical utility of sonography with Doppler examination in the diagnosis and treatment of gestational trophoblastic disease (GTD). METHODS: A retrospective analysis of 355 cases of GTD seen over a 12-year period in 2 large university referral hospitals in China was performed. Clinical appearances, sonographic findings, Doppler waveforms, and patient outcomes were reviewed. Sonographic and Doppler examinations were performed to diagnose the presence of molar tissue, detect invasive disease, assess disease recurrence, and monitor the efficacy of chemotherapy. Doppler waveforms of 13 patients with normal early pregnancies were also examined for comparison. RESULTS: Of the 355 patients with GTD, 106 had a classic hydatidiform mole (CHM), 33 had a partial hydatidiform mole (PHM), 184 had an invasive hydatidiform mole (IHM), and 32 had choriocarcinoma. Sonography showed abnormal molar tissue confined to the endometrial cavity in all cases of CHM. In cases of IHM and choriocarcinoma, soft tissue invasion and cystic vascular spaces within the myometrium were shown. Cases of PHM had a thickened, hydropic placenta with a concomitant fetus. Doppler waveforms showed resistive indices of 0.55 (SD, 0.06) for CHM, 0.56 (SD, 0.04) for PHM, 0.28 (SD, 0.06) for IHM, 0.25 (SD, 0.05) for choriocarcinoma, and 0.66 (SD, 0.04) for normal pregnancies. The abnormal sonographic and Doppler findings in invasive disease resolved when chemotherapy was successful. CONCLUSIONS: Sonography and Doppler imaging were helpful in diagnosing GTD, in determining whether invasive disease was present, in detecting recurrence of disease, and in following the effectiveness of chemotherapy.     

Treating gestational trophoblastic disease

Importance of the field: Gestational trophoblastic disease is one of the few human malignancies that is curable, even in advanced stages of the disease. However, appropriate management and follow-up are essential components in curing this disease.

Areas covered in this review: Observational, retrospective and prospective studies evaluating the efficacy of medical and surgical management of gestational trophoblastic disease were analyzed to provide a comprehensive review of current and new treatment modalities. We searched PubMed, Medline and the Library of Congress from January 1965 to January 2010.

What the reader will gain: The reader will obtain information on how to classify gestational trophoblastic neoplasia (GTN) into low- and high-risk groups, as well as learn the medical and surgical management of low- and high-risk GTN and recurrent GTN. The effectiveness of treatment regimens and subsequent fertility is also reviewed.

Take home message: GTN is highly responsive to chemotherapy. However, surgery is an important adjunct in select cases. Even in advanced-stage or recurrent disease, cure can be achieved and fertility preserved.     

NS mRNA表达检测对恶性葡萄胎的诊断意义

目的：探讨Nucleostemin基因（NS mRNA）表达检测对恶性葡萄胎的诊断意义。方法研究对象分为四组，A组为正常足月产孕妇，100例，采集羊水脱落细胞；B组为药物流产孕妇，100例，排除其他疾病，采集流产的胚胎绒毛组织； C组为良性葡萄胎患者，20例，采集葡萄胎组织和羊水脱落细胞；D组为恶性葡萄胎患者，19例，采集葡萄胎组织和羊水脱落细胞。采用Real-time PCR方法检测四组标本中Nucleostemin mRNA的表达水平。结果羊水脱落细胞和胚胎组织中Nucleostemin mRNA表达水平和阳性率以D组最高，C组次之。在羊水脱落细胞和胚胎组织中检测Nucleostemin mRNA，对于诊断恶性葡萄胎，敏感性、特异性和准确度均较好。结论 Nucleostemin基因高表达可能在葡萄胎的发生发展中起重要用，羊水脱落细胞和胚胎组织中Nucleostemin mRNA的检测有望成为恶性葡萄胎诊断的辅助指标。     

米非司酮抑制葡萄胎血管内皮生长因子与微血管密度生成及其对临床预后的影响

目的通过研究米非司酮治疗葡萄胎前后血管内皮生长因子(VEGF)及微血管密度(MVD)的改变,探讨米非司酮对滋养细胞肿瘤组织微血管生成的影响,寻求妊娠滋养细胞肿瘤治疗新途径。方法应用免疫组织化学方法染色检测32例葡萄胎组织的VEGF表达及MVD的改变;以正常早孕人工流产胚胎组织30例作为对照组。选取葡萄胎组织VEGF阳性表达病例11例,给予米非司酮治疗,1周后再次清宫,取组织重复染色,观察VEGF染色及MVD情况,分析米非司酮治疗对葡萄胎组织VEGF及MVD的影响。结果葡萄胎组织VEGF表达阳性率为34.4%,高于正常早孕人工流产胚胎组织的6.7%,VEGF阳性表达区多位于滋养细胞增生区或向正常组织浸润的边缘。米非司酮治疗前、后MVD值分别为43.03±10.11和21.32±8.03,差异有统计学意义(P<0.05)。全部治疗病例随访13～37个月,无一例进展成侵蚀性葡萄胎。结论葡萄胎组织VEGF高表达可能与肿瘤性滋养细胞的浸润性有关,米非司酮对葡萄胎组织新生血管形成具有抑制作用,对预后未见不良影响。     

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。