动脉栓塞治疗在妊娠滋养细胞肿瘤中的应用进展

妊娠滋养细胞肿瘤(gestational trophoblastic neoplasia,GTN)具有侵袭及破坏周围血管的特性,以血行转移为主,易出现子宫肌层及转移病灶大出血,危及患者生命安全。近年来随着放射介入技术的不断进展,动脉栓塞治疗越来越多地用于GTN,并作为急诊手术的替代方法治疗子宫病灶及转移病灶的出血,同时保留生育功能。GTN中子宫动静脉瘘存在重度出血的风险,彩色多普勒超声是筛查子宫动静脉瘘的首选方法,增强电子计算机断层扫描(CT)和磁共振成像(MRI)也具有较高的特异性,选择性盆腔动脉造影是明确诊断的金标准。良好的插管技术、精准的定位、栓塞剂的合理选用、剂量及速度的控制均不影响卵巢及生育功能,动脉栓塞为GTN患者尽早全身化疗提供时机。综述动脉栓塞治疗在GTN急性大出血和动静脉瘘的应用、栓塞剂的选择、栓塞术后对化疗和生育功能的影响及其并发症。     

复发性妊娠滋养细胞肿瘤的临床分析

目的:探讨复发性妊娠滋养细胞肿瘤(recurrent gestational trophoblastic neoplasia,recurrent GTN)的诊断方法与治疗措施。方法:回顾分析2000年6月～2009年6月浙江大学附属妇产科医院住院的复发性滋养细胞肿瘤21例患者的临床资料,并结合复习文献进行探讨。结果:在21例患者中,16例(76.2%)为单次复发,5例(23.8%)复发2次或者2次以上。复发的时间间隔分别为2个月～20年不等,其中12例(57.1%)在12个月内复发;9例(40.9%)在12个月后复发(其中4例在12～24个月复发)。16例为单次复发患者中13例直接采用EMA-CO化疗方案,10例经过3～7个疗程后达到血清学完全缓解(serologic comple teremission,SCR),2例效果不理想者采用EP-EMA化疗方案(1例辅以手术治疗)均在5个疗程后达到SCR,1例由于骨髓抑制严重,主动放弃治疗。5例多次复发患者中4例为2次复发,1例3次复发。4例2次复发的患者中,3例在第2次复发时采用EMA-CO化疗方案并在5～10个疗程后达到SCR,1例新发病灶切除术后放弃治疗。1例3次复发患者,3次治疗均达到SCR。21例患者中采用手术辅助治疗的有10例(47.6%),其中初次治疗时有5例(均为子宫切除),复发后7例[3例切除子宫,1例切除子宫病灶,2例切除转移病灶(2例初次治疗时切除子宫),1例分别切除转移病灶和子宫(2次复发,每次复发时手术)],切除子宫或者病灶后均得到不同程度的缓解。结论:以EMA为基础的联合化疗对复发性GTN患者有效,手术可作为复发性GTN的治疗辅助方式。     

高危妊娠滋养细胞肿瘤的治疗

高危妊娠滋养细胞肿瘤的治疗原则是联合化疗为主,手术、放疗、靶向和免疫等综合治疗为辅,总的来讲预后良好,但仍有患者因肿瘤复发耐药而死亡。文章对近年来高危妊娠滋养细胞肿瘤的治疗进展做一概述,为临床治疗提供参考。     

妊娠滋养细胞肿瘤46例临床分析

目的:分析妊娠滋养细胞肿瘤的临床特点及诊治经验,探讨其临床各期的治疗。方法:收集我院2000年1月至2007年6月收治的妊娠滋养细胞肿瘤46例患者的临床资料,分析其病史特点、发病规律、经化疗或化疗联合手术治疗后的临床转归。结果:46例中放弃治疗2例,44例患者经化疗或化疗结合手术治疗后完全恢复。其中绒毛膜癌11例,完全恢复11例,治愈7例,治愈率63.64%;侵蚀性葡萄胎33例,完全恢复33例,治愈22例,治愈率66.67%。结论:化疗是妊娠滋养细胞肿瘤主要的治疗方法。对有转移瘤破裂出血、不能确定诊断或对化疗耐药的患者,配合适当的手术治疗,疗效更佳。     

重视妊娠滋养细胞肿瘤的规范化治疗

妊娠滋养细胞肿瘤（gestational trophoblastic neoplasia,GTN）有着非常敏感和特异性的标志物——人绒毛膜促性腺激素（hCG）,且对化疗高度敏感,治愈率非常高［1］。低危GTN患者的总治愈率接近100%,高危患者的治愈率超过90%。     

妊娠滋养细胞肿瘤291例临床特征分析

目的:了解15年妊娠滋养细胞肿瘤(GTN)临床特征的变化趋势,以提高对本病的认识。方法:回顾性分析西安交通大学医学院第一附属医院1994年12月至2009年12月收治的291例GTN患者的临床资料,其中侵蚀性葡萄胎(IHM)221例及绒毛膜癌(CC)70例。以每5年为一个阶段分组,对其临床特征进行比较分析。结果:15年间IHM及CC的发生率无明显变化。IHM及CC患者的发病平均年龄在15年中均有所上升,2005～2009年组的年龄分布明显高于1994～1999年组和2000～2004年组(IHM:P=0.001,P=0.040;CC:P=0.050,P=0.015),特别是年龄>40岁患者,2005～2009年组所占比例也明显高于1994～1999年组和2000～2004年组(IHM:P=0.003,P=0.050;CC:P=0.040,P=0.010)。IHM及CC患者中无症状患者比例均有所上升;IHM患者间比较,差异有统计学意义(P=0.002,P=0.018,P=0.001),CC患者间比较,差异无统计学意义(P>0.05)。结论:近年来,GTN的发病年龄有增加趋势,特别是年龄>40岁患者明显增多;IHM中无症状患者比例上升。     

妊娠滋养细胞肿瘤患者保留生理功能的治疗

妊娠滋养细胞肿瘤以往均指侵蚀性葡萄胎和绒毛膜癌,自从对滋养细胞的分化进一步认识后,已知除细胞滋养细胞和合体滋养细胞外还有中间型滋养细胞.中间型滋养细胞中的种植部位中间型滋养细胞,部分可形成胎盘部位的滋养细胞肿瘤（PSTT）;绒毛膜型中间型滋养细胞,少数可形成上皮型滋养细胞肿瘤（ETT）.所以目前对妊娠滋养细胞肿瘤的认识,至少应该包括侵蚀性葡萄胎、绒毛膜癌、胎盘部位的滋养细胞肿瘤和上皮性滋养细胞肿瘤四种.有关对妊娠滋养细胞肿瘤保留生理功能的治疗也应包括上述四种类型的肿瘤,而保留生理功能应包括卵巢内分泌功能和生育功能,即对卵巢和子宫的保存及其能发挥功能问题.     

特殊病理类型妊娠滋养细胞肿瘤的治疗

特殊病理类型的妊娠滋养细胞肿瘤主要包括胎盘部位滋养细胞肿瘤（placental site trophoblastic tumour,PSTT）和上皮样滋养细胞肿瘤epithelioid trophoblastic tumour(ETT),属于中间型滋养细胞肿瘤。由于缺乏特异性的临床表现和敏感性的肿瘤标志物,诊断过程相对复杂。两者治疗主要以手术治疗为主,病灶局限于子宫时行子宫切除术,有子宫外转移或侵袭时,需同时切除可切除的病灶,根据预后不良因素制定辅助化疗方案。同时由于多数患者为育龄期妇女有保留生育功能的要求,对于病灶局限经过严格筛选的合适患者可以实施保留生育功能的治疗。PSTT和ETT对化疗敏感性均较差,化疗耐药仍然是预后不良的重要因素。由于发病率低,至今缺乏大样本的随机对照试验用于指导临床治疗,新的治疗方法如靶向治疗和免疫治疗等也在不断的探索中。     

妊娠滋养细胞肿瘤药物治疗研究进展

        妊娠滋养细胞肿瘤（gestational trophoblastic neoplasia,GTN）是一组与妊娠相关的恶性肿瘤,组织学上来源于胎盘滋养细胞,分为侵袭性葡萄胎（invasive mole,IM）、绒毛膜癌（choriocarcinoma,CC）、胎盘部位滋养细胞肿瘤（placental site trophoblastic tumour,PSTT）和上皮样滋养细胞肿瘤（epithelioid trophoblastic tumour ,ETT）。 浏览更多请关注本刊微信公众号及当期杂志。     

妊娠滋养细胞肿瘤的辅助治疗

妊娠滋养细胞肿瘤是一组来源于胎盘滋养细胞的疾病,包括侵蚀性葡萄胎、绒癌、胎盘部位滋养细胞肿瘤和上皮样滋养细胞肿瘤。前两者在临床上统称为妊娠滋养细胞肿瘤。总体来说,妊娠滋养细胞肿瘤     

恶性滋养细胞肿瘤的疗效和预后因素分析

目的:回顾分析1985年至2004年北京协和医院收治的恶性滋养细胞肿瘤患者的治疗和预后情况,并探讨影响其预后的相关因素。方法:1985年1月至2004年1月我院收治恶性滋养细胞肿瘤患者1 130例,其中侵蚀性葡萄胎(IM)患者614例,绒癌(CC)患者516例。其中高危患者325例,低危患者805例。回顾分析这些患者的治疗和预后,探讨影响预后的因素。结果:1 130例患者中903例(80.0%)获得完全缓解,187例(16.5%)获部分缓解,40例(3.5%)患者病情进展,64例患者(5.0%)在治疗中或病情缓解复发后死亡。CR患者中31例(3.4%)在停药后4个月~6年复发,共复发38例次。187例PR患者中155例患者(82.0%)经过化疗后β-hCG降至正常,但转移灶缩小至一定程度后未再有明显变化带瘤出院,其中17例患者未随诊,138例均定期随诊,其中84例随诊期间转移灶无明显变化,48例转移灶消失或缩小,此外6例(3.9%)绒癌患者在停药6~8个月后β-hCG升高,病情进展。通过统计学分析表明其与所有CR患者及合并肺转移的CR患者的预后之间均无明显的统计学差异(P>0.05)。随诊患者中139例患者停药后共妊娠159次,其中废胎率16.4%(26/159),葡萄胎率3.1%,胎儿畸形率1.6%(1/61)。结论:GTN患者经适时、规范的化疗多可治愈。对于高危和耐药的患者应采用多药联合及多途径方案化疗,对一些选择性病例同时辅助手术治疗,可提高治愈率。对于β-hCG正常后并经巩固化疗,转移灶不再变化的患者可认为是治愈而密切随诊。建议有生育要求的患者在停药1年后妊娠,并加强产前检查以预防发生异常妊娠。     

妊娠滋养细胞肿瘤的化疗

由于妊娠滋养细胞肿瘤(GTN)对化疗高度敏感,绒毛膜促性腺激素(HCG)可作为理想的肿瘤标志物,以及应用预后评分可使其治疗达到分层个体化,GTN成为了少数几个能通过化疗而达到治愈的肿瘤之一。文章介绍了近年来有关妊娠滋养细胞肿瘤化疗进展。     

妊娠滋养细胞肿瘤Ⅳ期患者的治疗和预后分析

目的 探讨和分析妊娠滋养细胞肿瘤Ⅳ期患者的治疗和预后.方法 1985年1月至2004年1月北京协和医院收治了妊娠滋养细胞肿瘤患者1130例,其中Ⅳ期患者92例,对这些患者的治疗及预后情况进行回顾性分析.结果 92例Ⅳ期患者中,有4例（4%）入院后尚未接受化疗即死亡,其余88例均接受了多药联合化疗,化疗方案采用以氟尿嘧啶为主的联合化疗方案,化疗途径主要是静脉途径以及动脉插管化疗;有32例（35%,32/92）患者在接受化疗的同时还予以手术治疗.92例患者经过治疗后33例获得完全缓解（CR）,37例部分缓解,22例病情进展.CR患者中3例复发.所有患者中共有33例死亡.92例患者中,70例患者有1个或2个脏器的转移,其中27例（39%,27/70）获得CR,20例（29%,20/70）死亡;出现3个脏器转移的17例患者中5例（29%,5/17）获得CR,10例（59%,10/17）死亡;≥4个脏器转移的5例患者中,1例获得CR,3例死亡.转移脏器数量的多少与患者的预后相关（P=0.034）,也与死亡相关（P=0.018）.结论 多药、多途径联合化疗辅助手术治疗是改善Ⅳ期患者预后的主要方法,对于不同脏器转移的治疗应该采用个体化方式.随着转移脏器数量的增加,缓解率明显降低.     

The prognosis of gestational trophoblastic neoplasia patient with residual lung tumor after completing treatment

OBJECTIVE: To analyze retrospectively the prognosis of gestational trophoblastic neoplasia (GTN) patients who achieved normal beta-hCG titer after completing treatment but remained with residual lung tumor. METHOD: A total of 1,130 GTN patients were hospitalized at Peking Union Medical College Hospital from January 1985 to January 2004. Among these patients, 901 achieved complete remission (CR); 152 achieved normal blood beta-hCG titer after the completion of treatment but remained with residual lung tumor (defined as partial remission). Retrospective analyses were carried out on the 152 patients. Statistical analysis was used to compare the recurrent rate of the CR patients with the progression rate of the 152 patients. RESULT: 17 of the 152 patients lost follow-up. Of the rest 135 patients followed up from 14 to 110 months, 83 showed no significant changes as to their residual tumors; 46 patients' residual tumors diminished or disappeared; and the other 6 patients got progression of disease (PD), with beta-hCG level going up 6-8 months after completing treatment. There is no significant statistical difference (P > 0.05) between the recurrent rate of the 901 CR patients and the progression rate of the 152 patients. There is also no significant statistical difference (P > 0.05) between the recurrent rate of the CR patients with lung metastasis and the progression rate of the 152 patients. CONCLUSION: After achieving normal beta-hCG titer, patients whose lung tumor stayed unchanged even following several additional courses of chemotherapy should be considered as CR patients. Follow-ups should be strictly carried out on these patients, especially at around 6 months after the completion of treatment, and particularly for high-risk and drug-resistant choriocarcinoma (CC) patients.     

Risk factors for gestational trophoblastic neoplasia

A case-control study to determine the gynecologic and reproductive risk factors for gestational trophoblastic neoplasia was conducted in the Baltimore Metropolitan Area. All cases (N = 190) that were pathologically diagnosed from 1975 to 1982 as hydatidiform mole, invasive mole, or choriocarcinoma were ascertained. Slides were independently reviewed by two pathologists. Cases were matched by age, race, and last menstrual period to controls who were delivered of normal pregnancies at term. In the analysis of medical record and interview data, factors found to be positively associated with gestational trophoblastic neoplasia included professional occupations (odds ratio = 2.56, p less than 0.0001), prior spontaneous abortions (odds ratio = 2.32, p = 0.02), and the mean number of months from the last pregnancy to the index pregnancy (cases = 35.9, controls = 28.2; p = 0.03). Factors found not to be associated with disease included contraceptive history, irradiation, ABO blood group, and smoking factors of the male partner. The findings suggest that gestational trophoblastic neoplasia may be part of a continuum of early (first-trimester) reproductive abnormalities.     

Poor-prognosis metastatic gestational trophoblastic neoplasia

Despite recent advances in therapy, patients with poor-prognosis metastatic GTN continue to present the clinician with challenging management problems. The optimal care for these patients is best delivered in centers specializing in the treatment of trophoblastic disease. Not only does the coordination of chronic aggressive multiagent chemotherapy, irradiation therapy, and surgical therapy require considerable expertise, but the proximity of a reliable and sensitive hCG assay aids in the rapid identification of the development of drug-resistant disease. Although recognition of the poor-prognosis group and the development of effective multiagent chemotherapy have increased the survival of these patients, progress in therapy for these patients will require continuing intensive efforts.     

Secondary chemotherapy for high-risk gestational trophoblastic neoplasia

OBJECTIVE: To determine the efficacy of secondary chemotherapy after failure of initial treatment for high-risk gestational trophoblastic neoplasia. METHODS: Twenty-six patients with high-risk gestational trophoblastic neoplasia based on WHO criteria who failed primary treatment or relapsed from remission and received secondary chemotherapy were identified from the records of the Brewer Trophoblastic Disease Center. Initial chemotherapy consisted of etoposide, high-dose methotrexate with folinic acid, actinomycin D, cyclophosphamide and vincristine (EMA-CO) in 10 patients and methotrexate/actinomycin D-based chemotherapy without etoposide in 16 patients. Secondary chemotherapy consisted mainly of platinum-etoposide combinations with methotrexate and actinomycin D (EMA-EP), bleomycin (BEP), or ifosfamide (VIP, ICE). Adjuvant surgery and radiotherapy were used in selected patients. Clinical response and survival as well as factors affecting survival were analyzed retrospectively. RESULTS: The overall survival has 61.5% (16/26). Of the 10 patients who failed primary treatment with EMA-CO, 9 (90%) had complete clinical responses to secondary chemotherapy with EMA-EP (3) or BEP (6), and 6 (60%) were placed into lasting remission. Of the 16 patients who failed primary treatment with methotrexate/actinomycin D-based chemotherapy without etoposide, 10 (63%) had complete clinical responses to BEP (8), VIP (1) and ICE (1), and 10 (63%) achieved long-term remission. Adjuvant surgical procedures were performed on 15 patients as a component of their therapy; eight (73%) of 11 patients who underwent hysterectomy, five (62%) of eight patients who had pulmonary resections, and one patient who had wedge resection of resistant choriocarcinoma from the uterus survived. Survival was significantly influenced by both hCG level at the start of secondary therapy and sites of metastases. CONCLUSION: Patients with persistent or recurrent high-risk gestational trophoblastic neoplasia who develop resistance to methotrexate-containing treatment protocols should be treated with drug combinations employing a platinum agent and etoposide with or without bleomycin or ifosfamide.     

化疗联合手术治疗高危型妊娠滋养细胞肿瘤25例分析

目的:分析高危型妊娠滋养细胞肿瘤治疗中手术的重要性。方法:收集我院自2000年1月～2010年8月间收治的高危型妊娠滋养细胞肿瘤患者的临床资料,分析其临床特点及手术联合化疗的临床转归。结果:25例中13例行次广泛子宫切除加双附件切除,2例行全子宫切除,其余10例分别行子宫病灶切除或子宫外转移灶切除术,除2例自动出院失访外,23例均获完全缓解,临床缓解率92%,平均化疗疗程5.8个。结论:在高危型妊娠滋养细胞肿瘤中应用强有力化疗的同时正确选择手术可有效地控制病情,减少化疗疗程,降低化疗副反应,提高治愈率。     

妊娠滋养细胞肿瘤患者的死亡原因及相关因素分析

目的探讨妊娠滋养细胞肿瘤患者的死亡原因及相关因素。方法自1985年1月至2004年1月,北京协和医院共收治妊娠滋养细胞肿瘤患者1130例,其中死亡患者64例,本研究对这些患者的死亡原因及相关因素进行回顾性分析。结果64例死亡患者中,初治失败死亡58例,缓解后复发死亡6例;初治失败死亡患者的主要死亡原因为多器官功能衰竭、颅内出血或合并脑疝形成、化疗副反应;缓解后复发死亡患者的死亡原因为复发后病情进展。对初治失败患者的死亡原因进行单因素和多因素分析发现,初治失败患者的死亡与末次妊娠终止至化疗开始的时间（OR=2．857,P〈0．01）、血人绒毛膜促性腺激素β亚单位（β-hCG）水平（P〈0．05）、临床病理类型（OR=3．635,P〈0．05）、临床分期（P〈0．05）以及器官转移数目（OR=2．201,P〈0．01）、耐药（OR=0．181,P〈0．01）有关。结论妊娠滋养细胞肿瘤治疗前应对患者进行正确评估,重视与死亡相关的各种高危因素,以进一步改善患者预后。