侵蚀性葡萄胎转移的相关因素及疗效分析

目的:探讨侵蚀性葡萄胎(IHM)发生转移的相关因素及对其疗效进行对比分析。方法:回顾性分析2012年6月至2018年3月重庆医科大学附属第一医院收治的IHM 50例患者的临床资料,其中发生转移的24例(肺转移22例,阴道转移2例)为转移组,未见明确转移征象的26例为未转移组,对两组患者的相关临床特点进行Logistic多因素回归分析。并对其疗程、临床疗效、预后等资料进行对比研究。结果:①Logistic多因素回归分析示:停经距第1次清宫时间长、合并卵巢黄素化囊肿为IHM转移的独立危险因素(OR>1,P<0.05),而伴有假孕症状为IHM转移的保护性因素(OR<1,P<0.05)。②两组治疗情况比较,转移组开始治疗距血β-hCG转阴时间(70.00±21.07天)长于未转移组(57.27±16.75天),差异有统计学意义(P<0.05),而两组行化疗次数及全子宫切除术、近期治愈、近期好转、再次妊娠、复发的比例比较,差异均无统计学意义(P>0.05)。两组近期未治愈共9例患者均为未按时返院化疗。结论:一旦考虑诊断葡萄胎,应尽早行清宫术,以减少IHM转移的发生。合并卵巢黄素化囊肿的IHM患者需警惕是否有转移。在治疗时需严密监测血β-hCG水平的变化。IHM即使发生转移,经过规范的治疗仍能达到满意疗效。     

多囊性肾脏发育不良胎儿的遗传学检测及妊娠结局分析

目的:评估预防性子宫切除对40岁以上葡萄胎患者恶变为妊娠滋养细胞肿瘤(GTN)的治疗效果。方法:回顾性分析南京医科大学附属妇产医院2012年1月至2020年5月期间收治40岁以上葡萄胎患者共78例,其中预防性子宫切除患者40例、期待治疗患者38例,对相关临床资料进行分析。结果:预防性子宫切除组葡萄胎恶变率(37.5%)与期待治疗组(50.0%)比较,差异无统计学意义((印)P(正)>0.05);恶变组的平均停经时间(10.92±3.65周)较治愈组(8.36±4.35周)长,差异有统计学意义((印)P(正)<0.05);期待治疗后GTN化疗前血β-hCG数值、化疗疗程及耐药率较预防性子宫切除后GTN高,差异有统计学意义((印)P(正)<0.05)。结论:对于40岁以上的葡萄胎患者,预防性子宫切除可以提高GTN的早期诊断率,降低化疗量,且无增加转移病灶的风险,可以作为有效的治疗策略。     

侵蚀性葡萄胎阴道转移一例

一、病例摘要患者22岁,因"停经3个月余,葡萄胎清宫术后5周,阴道大量出血1h"于2012年5月26日16:55急诊收入北京大学人民医院。患者平素月经规律,末次月经2012年2月10日,孕1产0。停经30余天查血绒毛膜促性腺激素(hCG)升高,停经2个月时出现少量阴道出血,外院B超诊断"宫腔内异常回声,葡萄胎不除外"行清宫术,术后阴道出血淋漓不尽,定期复查血β-hCG,术后1个     

有恶变高危因素的葡萄胎患者预防性化疗的结局及临床特点分析

目的 分析有恶变高危因素的葡萄胎患者行预防性化疗的结局及临床特点.方法 回顾性分析2005年1月至2008年1月间在北京协和医院妇产科行清宫术后病理检查诊断为葡萄胎,并因具有高危因素而行预防性化疗的患者共23例,预防性化疗方案为单药化疗,如出现单药耐药即诊断为预防性化疗失败,葡萄胎患者发生了恶变,随后给予双药或多药联合方案化疗.其中,预防性化疗成功11例(成功组),失败12例(失败组),比较两组患者的临床特点及预防性化疗结局.结果 成功组和失败组患者的中位年龄分别为33.1和30.0岁,中位停经时间分别为12.3和12.1周,子宫增大至相应停经周数4周以上者分别为4/11和4/12,单侧卵巢囊肿直径≥6cm或有双侧卵巢囊肿者分别为1/11和4/12,以上指标两组间分别比较,差异均无统计学意义(P＞0.05).成功组与失败组清宫术前血清β-hCG的中位水平分别为469 144和768 044 U/L,开始治疗至首次血清β-hCG水平降到正常水平(正常≤2 U/L)的中位治疗时间分别为71和120 d,两组分别比较,差异均有统计学意义(P＜0.05,P＜0.01).受试者工作特征(ROC)曲线分析显示,血清β-hCG水平可作为提示预后的指标;以750 000 U/L作为截距值,其特异度为91%,敏感度为58%.结论 对于血清β-hCG水平高于750 000 U/L的葡萄胎患者,需要进行预防性化疗,最好直接采用双药或多药联合方案的化疗,以利于缩短治疗时间及预防耐药.

Abstract：

Objective To analyze prophylactic chemotherapy outcome and clinical characteristics in patients of high-risk hydatidiform mole. Methods Twenty-three patients who were diagnosed as high-risk hydatidiform mole and undergone prophylactic chemotherapy in our hospital were retrospectively analyzed.After prophylactic chemotherapy, 11 patients didn't develop to gestational trophoblastic neoplasia (GTN),while the other 12 patients developed to GTN and needed a regimen change to combination chemotherapy.The clinical characteristics of these patients and outcome of prophylactic chemotherapy were compared between two groups. Results There was no significant difference between the two groups on patients' age,weeks of delayed menses, enlarged uterine size excessive for gestational age, and incidence of theca-lutein cysts of ovaries. However,the median levels of pre-evacuation serum β-hCG in two groups were 469 144 U/L and 768 044 U/L respectively, and median days needed for β-hCG declining to normal(≤2U/L) at the first time were 71 and 120 days respectively, which were both significantly different between two groups.Analyzed with receiver operating charactristic(ROC), the level of serum β-hCG could be a predictor for prognosis. Choosing 750 000 U/L as the cut-off value, we could expect the serum β-hCG to have a specificity of 91% and a sensitivity of 58% to predict whether prophylactic chemotherapy will be successful.Conclusions For those patients who have to receive prophylactic chemotherapy because of risk factors and unavailable hCG assessments for follow-up, it's better to use double-agent or combination chemotherapy if the level of serum β-hCG reached 750 000 U/L so as to reduce therapy duration and prevent relevant chemoresistance.     

剖宫产术后子宫瘢痕部位妊娠96例临床分析

目的 探讨剖宫产术后子宫瘢痕部位妊娠(CSP)的临床表现、诊断依据、治疗方法和卫生经济学特点.方法 回顾性分析复旦大学附属妇产科医院2005年1月至2008年12月收治的96例CSP患者的临床资料,按不同治疗方法分为A组33例,行甲氨蝶呤(MTX)50 mg/m2静脉滴注,其中18例MTX静脉治疗后5～10 d内行清宫术(MTX+清宫);15例先行清宫术,术后每48小时复查1次血人绒毛膜促性腺激素β亚单位(β-hCG)水平,3次均下降不足30%者,再用MTX 50 mg/m2静脉滴注治疗(清宫+MTX).B组60例,行MTX双侧子宫动脉介入栓塞治疗,每侧子宫动脉注入MTX 100 mg,术后2 d内行清宫术.C组3例,行子宫病灶切除术.比较各组出血量(M)、病灶直径(-x±s)、治疗前血β-hCG水平(M)、病灶距子宫浆膜层≤3mm的例数、病灶血流阻力指数(RI)≤0.5的例数、治疗费用(-x±s)、住院时间(-x±s)的差异,并分析出血量与病灶直径和血β-hCG水平的相关性.结果 (1)临床指标:出血量:A组MTX+清宫者为20 ml、清宫+MTX者为10 ml,B组为12 ml,C组为200ml,C组与A、B组比较,差异有统计学意义(P＜0.01);病灶直径:A组MTX+清宫者为(16±8)mm、清宫+MTX者为(23±15)mm,B组为(30±14)mm,显著高于A组MTX+清宫者,差异有统计学意义(P＜0.01),C组为(52±7)mm,3组分别比较,差异均有统计学意义(P＜0.01);治疗前血β-hCG水平:A组MTX+清宫者为21 592 U/L、清宫+MTX者为979 U/L,两者比较,差异有统计学意义(P＜0.05),B组为11 312 U/L,C组为101 U/L,C组与A、B组比较,差异均有统计学意义(P＜0.05);病灶血流RI0.5共28例,其中A组8例(24%,8/33)、B组18例(30%,18/60),C组2例(2/3),C组高于其他两组,差异有统计学意义(P＜0.05);病灶距子宫浆膜层≤3 mm共23例:A组2例(6%,2/33),B组21例(35%,21/60),C组0例,B组高于其他两组,差异也有统计学意义(P＜0.05);治疗费用:A组MTX+清宫者为(5578±3679)元、清宫+MTX者为(5346±2765)元,两者比较,差异无统计学意义(P＞0.05),B组为(7860±2104)元,C组为(5004±421)元,B组高于A、C组,差异有统计学意义(P＜0.05);住院时间:A组MTX+清宫者为(15±8)d、清宫+MTX者为(19±14)d,B组为(16±10)d,C组为(17±8)d,各组比较,差异均无统计学意义(P＞0.05).(2)相关性:出血量与子宫病灶直径(r=0.31,P＜0.05)以及治疗前血β-hCG水平(r=0.35,P＜0.05)均呈正相关关系.结论 MTX静脉治疗、动脉介入栓塞治疗和子宫病灶切除术用于治疗CSP,如应用恰当都能取得良好效果;病灶大、血β-hCG水平高、病灶距浆膜层近或子宫病灶血液供应丰富时,可选择MTX子宫动脉介入栓塞+清宫术治疗,但费用较高.     

妊娠滋养细胞肿瘤治疗后肺内阴影持续存在患者的预后分析

目的 分析妊娠滋养细胞肿瘤肺转移患者经规范治疗后,血人绒毛膜促性腺激素13亚单位（13．hCG）水平降至正常,但肺内阴影持续存在患者的预后。方法 1985年1月至2004年1月间北京协和医院共收治了妊娠滋养细胞肿瘤患者1130例,其中获得完全缓解（CR）患者901例,获得部分缓解（PR）患者187例。901例CR患者中合并肺转移者463例;187例PR患者中152例经规范化疗后血β-hCG水平降至正常,但肺内转移灶未完全吸收而带瘤出院随诊。本研究对上述152例肺内带瘤出院患者的临床资料进行回顾性分析,并分别与同期出院的901例CR患者以及合并肺转移的463例CR患者的预后进行比较。结果 152例患者均接受了规范的多疗程多药联合化疗1．30个疗程（平均3．6个疗程）后血β-hCG水平降至正常,然后又接受了0—8个疗程（平均3．7个疗程）的巩固化疗而带瘤出院。152例肺内带瘤出院患者中,除17例患者未随诊外,其余135例患者均定期随诊,随诊时间为14—110个月。其中,83例患者随诊期间肺内阴影没有明显变化;46例患者肺内阴影消失或缩小;6例（均为绒毛膜癌）患者在停药6—8个月后血β-hCG水平升高,病情进展。152例肺内带瘤出院患者的病情进展率为3．9％（6／152）,分别与901例CR患者的复发率[3．4％（31／901）]以及463例合并肺转移CR患者的复发率[2．2％（10／463）]比较,差异均无统计学意义（P〉0．05）。结论 妊娠滋养细胞肿瘤肺转移患者经规范治疗后血β-hCG水平降至正常,再经过2．4个疗程的巩固化疗后其肺内阴影不再继续缩小或消失者,多为肺内转移灶坏死或局部纤维化,可以认为其为CR。但出院后应密切随诊,尤其是停药6个月左右的绒毛膜癌患者。     

绒癌和侵蚀性葡萄胎患者化疗后一年内妊娠结局的分析

目的　探讨绒癌和侵蚀性葡萄胎患者多疗程化学治疗（ 化疗） 后,１ 年内妊娠的结局。方法　分析绒癌和侵蚀性葡萄胎患者化疗后在１ 年内妊娠的２２ 例发生异常妊娠、废胎率的情况及其与化疗停药的间隔的关系。结果　２２ 例中,足月分娩９ 例,废胎６ 例,废胎率为２７．３％ 。其中停止化疗半年内妊娠者废胎率高于半年以上者（ Ｐ＜ ０．０５）。患者发生产后绒癌１ 例,发生重复性葡萄胎１ 例,此２ 例均发生在停药５ 个月内妊娠。结论　绒癌和侵蚀性葡萄胎经化疗保留子宫是可行的。但多疗程化疗后,妊娠不宜太早,应至少避孕半年,最好避孕１ 年。     

恶性滋养细胞肿瘤肺转移患者肺叶切除术指征的探讨

目的探讨肺叶切除术治疗恶性滋养细胞肿瘤肺转移患者的手术指征。方法通过医院病案数据库,调用1990—2003年北京协和医院收治的629例Ⅲ~Ⅳ期恶性滋养细胞肿瘤患者的治疗记录,收集肺转移行肺叶切除术的患者及化疗后血人绒毛膜促性腺激素β亚单位(βhCG)降至正常(<2IU/L)后肺内带瘤随诊的患者,对符合入选条件的95例患者的临床病理资料进行回顾性分析。结果侵蚀性葡萄胎肺转移患者41例中,行肺叶切除术者6例,病理检查病灶全为坏死结节;化疗后血βhCG正常后肺内带瘤随诊者35例,随诊6个月~11年,病情均稳定。绒毛膜癌肺转移患者54例中,行肺叶切除术者29例,其中病理检查病灶为出血坏死组织、无活性肿瘤细胞者(定为病理阴性)17例,病灶内仍有活性肿瘤细胞残留者(定为病理阳性)12例;化疗后血βhCG正常未手术的带瘤随诊者25例,其中病情进展5例,病情稳定20例。绒毛膜癌肺叶切除术后病理阳性及带瘤随诊病情进展患者在年龄、临床分期、末次妊娠性质等方面与肺叶切除术后病理阴性及带瘤随诊病情稳定患者比较,差异无统计学意义(P>005);但两者血βhCG从10IU/L降到2IU/L以下所需的化疗疗程数及总疗程数比较,前者却明显多于后者(P=001,P=0001)。结论侵蚀性葡萄胎肺转移可经化疗治愈,化疗后未完全消失的肺部阴影可随诊观察。     

经阴道彩色多普勒技术对侵蚀性葡萄胎的临床应用价值

葡萄胎清宫以后,能否早期发现病变侵蚀子宫肌壁,为提高治愈率重要环节之一。本文应用经阴道彩色多普勒超声(TVCD)检查葡萄胎患者,以探讨TVCD对侵蚀性葡萄胎的早期诊断、判断化疗效果、预测病变转归方面的临床应用价值。 资料和方法 一、研究对象 选择我院1996年10月～2000年12月间住院和门诊侵蚀性葡萄胎83例患者,平均年龄32.5岁(20～45岁)。所有病例每次化疗前后均行TVCD及胸片检查,并测血β-     

葡萄胎患者清宫化疗后再次妊娠适宜时间的探讨

目的 :探讨葡萄胎患者清宫、预防性化疗后再次妊娠的适宜时间。方法 :为1988年 1月至 1995年 1月住院的葡萄胎患者制定系统化治疗方案 ,出院后定期随访 ,根据清宫后再次妊娠的时间分为 3组 ,分别观察对母婴健康的影响。结果 :清宫后 7～ 2 4个月妊娠者与清宫后超过 2 4个月妊娠者母婴健康情况差异无显著性 (P >0 .0 5 )。结论 :葡萄胎患者治疗后 ,β HCG降至正常水平 ,持续半年 ,又无异常临床表现 ,希望妊娠者可解除避孕措施。     

Role of plasma nitric oxide in complete hydatidiform mole

PURPOSE OF INVESTIGATION: This prospective study aimed to evaluate any relationship between development of complete hydatidiform mole and plasma levels of nitric oxide (a biologically active mediator derived from L-arginine), and human chorionic gonadotropin beta (beta-hCG; a metabolite involved in trophoblast production). METHODS: Levels of plasma nitric oxide and beta-hCG were measured in 38 patients with complete hydatidiform mole pregnancies, and nitric oxide levels were measured in 31 women with normal pregnancies who formed the control group. RESULTS: For patients compared with controls, mean plasma concentrations of nitric oxide were significantly higher (35.84 vs 29.54 microM; p < 0.001) and significantly associated with increased risk of hydatidiform mole (odds ratio 1.0105, 95% confidence interval 1.0034-1.0176). No significant relationship was found between plasma levels of nitric oxide and beta-hCG in the patient group. CONCLUSION: In patients with complete hydatidiform mole compared with controls, plasma nitric oxide levels were found to be significantly higher and associated with increased molar risk.     

Partial mole with lung metastases and multiple abnormalities of the fetus

The authors report on a patient with partial mole, multiple malformations and lung metastases requiring chemotherapy. This case shows that the partial hydatidiform mole must therefore be carefully monitored by serial beta-hCG titres following evacuation to ensure the achievement of complete sustained remission.     

Overdiagnosis of complete and partial hydatidiform mole in tubal ectopic pregnancies.

Partial or complete hydatidiform mole (HM) affects approximately 1 in 500 to 1,000 pregnancies. Previous small series suggest that histopathologic diagnosis of HM may be difficult in tubal ectopic pregnancies. The histopathology database of a regional Trophoblastic Disease Unit was searched to identify cases with a referral diagnosis of tubal HM, and the histopathologic findings were reviewed. During the study period (1986-2004 inclusive), there were 132 cases. After central review by specialist histopathologists, the final diagnosis was ectopic partial mole in two, ectopic complete mole in five, and ectopic hydatidiform mole (not otherwise specified) in one. The final diagnosis of definite hydatidiform mole was made in eight (6%) cases, significantly less than in referred uterine curettage specimens, in which approximately 90% have a confirmatory diagnosis of HM (Z = 12.9; p < 0.0001). No cases in this series developed persistent gestational trophoblastic disease, the human chorionic gonadotropin concentration spontaneously returning to normal. Ectopic pregnancies, where managed surgically, should be submitted for histopathologic examination; however, the pathologist should be aware that the degree of extravillus trophoblastic proliferation may appear more florid compared with evacuated uterine products of conception. Molar pregnancy should only be diagnosed when strict criteria regarding morphologic abnormalities previously described in uterine evacuation material are applied.     

Gestational trophoblastic diseases: the ratio of choriogonadotropin to specific pregnancy protein, hCG/SP1, provides useful diagnostic and prognostic evidence

Serum levels of human chorionic gonadotropin (hCG), specific pregnancy protein (SP1), and hPL were measured in 675 samples from women with uneventful pregnancy, and serially from the time of presentation in 125 patients with hydatidiform mole (HM), 43 with invasive mole (IM), and 34 with choriocarcinoma (CC). In HM serum levels of hCG and SP1 declined steadily from presentation to remission; when gestational age at the time of molar evacuation was shorter than 11 weeks, hCG declined to the normal range later than SP1 (57% patients), and when the age was longer--at the same rate as SP1 (26% patients) or earlier (17% patients). Serum levels of either marker were higher in IM than in HM and tended to increase, and in CC were either lower or higher than in IM. Treatment was followed by parallel decline of either marker, although SP1 declined to the normal range later than hCG in 12% of patients with IM and in 10% with CC. The hCG/SP1 ratios in normal pregnancy declined exponentially between the beginning and 23rd week of gestation and stayed level thereafter. The ratios calculated for the gestational age at the time of initial evacuation of the uterus or delivery were close to those of normal pregnancy in 80%, slightly increased in 20% of patients with spontaneously regressing HM, and markedly increased in 70% of patients with IM and in 74% of patients with CC. The ratios tended to increase during chemotherapy. An increase in the hCG/SP1 ratio seemed to be a characteristic sign of malignant change when compared with this ratio in normal pregnancy and hydatidiform mole. Determination of SP1 for monitoring therapy seemed redundant, and hPL assay was useful for discrimination between relapse and pregnancy.     

Serum relaxin in patients with hydatidiform mole

Human chorionic gonadotropin (hCG) is considered to be one of the factors that regulates relaxin secretion in humans. However, the secretory pattern of relaxin has not been evaluated in pregnancy complicated by hydatidiform mole, where circulating hCG levels are higher than in normal pregnancy. In the present study, relaxin, progesterone, and hCG levels were determined by radioimmunoassay in patients with hydatidiform mole before and after evacuation of the mole. Serum immunoreactive relaxin and progesterone levels in patients with hydatidiform mole were similar to those in normal women at corresponding weeks of pregnancy before evacuation of the mole, though hCG levels were significantly higher. The fall of relaxin levels after evacuation of the mole was slower than that of hCG or progesterone. This finding may reflect a continued stimulation of the corpus luteum by lower, but still effective, hCG levels persisting after evacuation of the mole. An extraluteal source of relaxin cannot be excluded.     

Diagnostic reliability of simultaneous measurements of beta human chorionic gonadotropin and pregnancy-specific beta-1-glycoprotein in serum of patients with trophoblastic disease

Serum levels for beta-human chorionic gonadotropin (beta-hCG) and pregnancy-specific beta 1-glycoprotein (SP1) in patients with trophoblastic disease were measured by radioimmunoassay and enzyme-linked immunosorbent assay. The beta-hCG:SP1 ratios were below 1.0 in all 22 cases of complete hydatidiform mole and in 8 of 9 cases of partial hydatidiform mole. Two (10.5%) of 19 cases of invasive mole involving metastasis had ratios that rose above 1.0 during chemotherapy. Ratios ranged from 1.6 to 29 in 11 of 15 cases of choriocarcinoma before chemotherapy. The remaining 4 cases, diagnosed within 3 months of antecedent pregnancy, had ratios below 0.99. Thus, the difference between choriocarcinoma and nonchoriocarcinoma beta-hCG:SP1 ratios may be due to trophoblastic differentiation based on the developmental stage and with trophoblast age, or due to the mass and potential activity of trophoblastic cells.     

MMP-7与MMP-26在葡萄胎组织中的表达及临床意义

目的:检测MMP-7、MMP-26在正常早孕绒毛和葡萄胎组织中的表达,为研究葡萄胎的发生与临床诊治提供依据。方法:通过免疫组化SABC法检测20例葡萄胎及10例正常早孕绒毛组织中MMP-7、MMP-26表达,对结果进行统计学分析。结果:MMP-7在正常早孕绒毛组和葡萄胎组中的表达阳性率分别为60%和45%,差异无统计学意义;MMP-26在正常早孕绒毛组和葡萄胎组表达阳性率分别为90%和45.1%,差异具有统计学意义。MMP-7、MMP-26的表达与葡萄胎恶变高危因素无统计学相关性。结论:MMP-26可能与葡萄胎的发生有关;MMP-7与葡萄胎发生的关系有待进一步研究。     

Telomerase activity in complete hydatidiform mole.

OBJECTIVE: To investigate whether telomerase is activated in complete hydatidiform mole and whether it could predict the development of persistent gestational trophoblastic tumors (GTTs). STUDY DESIGN: For this prospective study, 21 patients with complete hydatidiform mole were recruited. Molar tissue was obtained for telomerase activity measurement using the telomeric repeat amplification protocol assay. Patients' clinical characteristics, telomerase activity and subsequent clinical outcome were analyzed. RESULTS: Telomerase activity was detected in 12 cases (57.1%) with varied intensity. Two of four patients who had telomerase activity, uterine size larger than expected and preevacuation serum beta-human chorionic gonadotropin (beta-hCG) levels > 10(6) mIU/mL developed persistent GTT. CONCLUSION: Telomerase activity is detectable in some complete hydatidiform moles and might be useful for predicting persistent GTT when combined with uterine size and preevacuation serum beta-hCG level.     

20年前后两组葡萄胎恶变患者的对比分析

目的 了解葡萄胎恶变后有关临床经过。方法 对我院1973年1月-1978年3月收治的151例(前期组)与1994年1月～1998年12月收治的132例(后期组)葡萄胎恶变病例进行回顾性的对比分析。结果 年龄<30岁者两组分别为57.4％和78.8%,>40岁者所占比例降低;首次妊娠为葡萄胎恶变者百分率增高,已生育一胎再次患本病者比例下降;前、后期患者职业均以农民为主,分别为90.3％和74.2％;阴道不规则出血者明显减少,入院时子宫增大比例降低,卵巢黄素囊肿发生率降低,分别为52.98％和26.5％;发生恶变距确诊葡萄胎之时间,前、后期两组相仿,大多在葡萄胎后半年之内发生恶变;转移部位均以肺、阴道为最多,CT可提高诊断肺转移正确性;恶变者主要采用化疗,子宫切除者逐渐减少。结论 对葡萄胎的早期诊断和规范化治疗可减少葡萄胎恶变率。