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Objective: To analyze the clinical characters and prognosis of postpartum choriocarcinoma., Methods: Retrospective analysis of 103 patients diagnosed with postpartum choriocarcinoma in Peking Union Medical College Hospital between 1985 and 2005 was performed., Results: In a total of 103 cases of postpartum choriocarcinoma treated with multiagent cytotoxic chemotherapy and combined modality therapy, 92 patients (89.3%) achieved a complete remission while 2 patients had a partial remission, and 9 patients died. Regarding 25 cases with chemorefractory choriocarcinoma and 4 relapsed cases, 18 and 3 cases achieved a complete remission respectively. According to the new International Federation of Gynecology and Obstetrics (FIGO) 2000 staging and risk factor scoring system, 17 cases were at FIGO stage I, 8 cases at stage II, 56 cases at stage III, and 22 cases at stage IV. Complete remission was achieved in 100%, 8/8, 95% and 64% respectively. Thirty-five cases in low risk group had FIGO scores < or = 6, and all achieved a complete remission. Of 68 cases in high risk group with FIGO scores > or = 7, 57 (84%) of them obtained a complete remission. There were significant differences in the two groups (P < 0.05)., Conclusion: Postpartum choriocarcinoma could have an increasing probability of cure with early diagnosis and the use of modern multiagent cytotoxic chemotherapy and combined modality therapy.

Objective: To investigate the clinical characteristics, management and prognosis of gestational trophoblastic disease in women aged 50 years or more., Methods: Thirty-eight cases of gestational trophoblastic disease in women aged 50 years or more, who were treated in Peking Union Medical College Hospital between 1992 and 2002, were reviewed retrospectively., Results: The median age was 52 years (range from 50 to 58 years). The lesions included 5 hydatidiform moles (13%), 19 invasive moles (50%), 12 choriocarcinomas (32%) and 2 placenta site trophoblastic tumors (5%). All of 38 cases presented with abnormal vaginal bleeding. Twenty-three cases of hydatidiform moles were diagnosed at their first visit to the hospital, and 15 of them received prophylactic chemotherapy, of whom 10 progressed to invasive mole, 3 developed lung metastasis. All of the other 8 cases without prophylactic chemotherapy progressed to malignant changes with metastasis of lung. The use of prophylactic chemotherapy reduced the incidence of subsequent metastasis. All of 38 cases received chemotherapy. Thirty-two cases underwent hysterectomy, complete remission was achieved in 91% of patients; complete remission was achieved in 2 of 6 patients without hysterectomy., Conclusions: The diagnosis of pregnancy and pregnancy-related disease should be considered in the elderly women presenting with abnormal vaginal bleeding. Once gestational trophoblastic disease in women aged 50 years or more is diagnosed, chemotherapy should be given as soon as possible. Hysterectomy is frequently required to improve the prognosis of gestational trophoblastic disease in the elderly women.

Objective: To investigate the indication of lung lobectomy in patients of malignant trophoblastic tumor with lung metastasis., Methods: Data on a total of 629 cases of malignant trophoblastic tumor of stage III-IV in Peking Union Medical College Hospital from 1990 to 2003 were reviewed. Ninety-five cases including those that underwent lung lobectomy and cases with normal level of serum human chorionic gonadotropin-beta subunit (beta-hCG, < 2 IU/L) and residual pulmonary nodules after chemotherapy were selected and studied., Results: Lung lobectomies were performed on six cases of invasive mole with lung metastasis and the pathological results were all necrotic nodules;another 35 cases of invasive mole with normal level of serum beta-hCG but residual pulmonary nodules after chemotherapy have been followed up for 6 months to 11 years and all were stable of diseases (SD). Lung lobectomies were performed on 29 cases of choriocarcinoma with lung metastasis. Among them, there were 17 cases whose pathological results were hemorrhage and necrotic tissue without trophoblastic cells (negative pathological results), while trophoblastic cells could still be detected in 12 cases of resected lung specimens (positive pathological results). Twenty-five cases of choriocarcinoma with normal serum beta-hCG but residual pulmonary nodules after chemotherapy were followed up, five cases had progress of disease (PD) and 20 were SD. There were no significant differences of age, stage and the last pregnancy between the positive and negative pathological results, SD and PD groups, respectively. However, the number of chemotherapeutic courses for decreasing beta-hCG from 10 IU/L to 2 IU/L and the total courses in the group of positive pathological results and PD group were significantly more than that of negative pathological results group and SD group (P = 0.01, P = 0.001)., Conclusions: For invasive mole, lung metastasis can be successfully treated by chemotherapy alone. Patients with residual pulmonary nodules but normal serum beta-hCG after chemotherapy can be followed up and spared lung lobectomy. For choriocarcinoma, slowly decreasing of beta-hCG from 10 IU/L to 2 IU/L is a high risk for chemoresistance, and it is an indication for thoracotomy. Progression of disease after multiple chemotherapy courses should be treated with lung lobectomy.

Objective: To assess malignant trophoblastic neoplasia with the standards of the clinical stage and prognostic factor scoring system., Methods: Through assessing the high-risk factors except clinical stages for 223 patients before treatment according to International Federation of Gynecology and Obstetrics (FIGO) scoring system published in 2000, appropriate treatments were selected for the different patients., Results: Forty-three of 78 cases of choriocarcinomas were with high-risk factors, the other 35 cases were with low-risk factors; 7 of 145 cases of invasive moles were with high-risk factors and the others were with low-risk factors. The primary chemotherapy principle was that one agent was used for those patients with low-risk factors and two or multiple-agents were used for those patients with high-risk factors. Among all patients, the one-year, three-year and five-year survival rates were 98.6%, 98.1% and 97.1% respectively. No patient died of drug toxicity or complication., Conclusion: Selection of treatment approaches according to the prognostic assessment of malignant trophoblastic neoplasia could lead to promising survival rate with no uncurable complication and toxic effects.

Objective: To identify the molecular components involved in acquired methotrexate-resistance of human choriocarcinoma., Methods: Methotrexate-resistant cell line (JAR/MTX) was derived from JAR cell line by exposed to intervally and progressively increasing higher concentration of MTX. cDNA microarray analyses of JAR/MTX and its parental cell line JAR were performed., Results: JAR/MTX was established after one year with stable resistance. Its resistant index to MTX was 7.3. Nine genes were differential expressed between JAR/MTX and JAR cells. INSR, SLC1A3, SAT, HBB, and FLJ12443 were underexpressed and HS1, TXNRD1, TAGLN2, and EEF2 were overexpressed in JAR/MTX cells., Conclusion: The cDNA microarray system showed that several alterations of gene expression were present in acquired methotrexate-resistance of human choriocarcinoma.

Objective: To establish a methotrexate (MTX)-resistant choriocarcinoma cell line and to determine its biologic characteristics., Methods: MTX-resistant cell line (JAR/MTX) was derived from human choriocarcinoma cell line JAR by exposed to intermittently and progressively increasing concentration of MTX. Drug sensitivity was detected by MTT; P-gp GST-Pi and PCNA expressions were detected by immunohistochemistry. Cell apoptosis was detected by flow cytometry (FCM) with PI/Annexin V stain. Growth rates and human chorionic gonadotropin (HCG) production were also measured., Results: JAR/MTX cell line was established with stable MTX-resistance (resistance index to MTX was 7.3) and cross-resistant to TAX and VCR. Growthrate of JAR/MTX was lower than that of parent cell line JAR. Expression level of PCNA in JAR/MTX was lower than that in JAR (3.09+/-0.42 compared with 3.72+/-0.35, P<0.05), while GST-pi expression was higher. No statistical difference of P-gp expression existed between two cell lines. JAR/MTX secreted more HCG than JAR every 10(5) cells secreted (95.7+/-5.4 compared with 41.3+/-2.8)mIU after 48 h(P<0.01). The flow cytometry showed that the spontaneous and MTX induced apoptosis in JAR/MTX was significantly lower than that in JAR P<0.05., Conclusion: JAR/MTX cell line presented stable resistant to MTX and cross-resistant to TAX and VCR, which might sever as a model in study of drug resistance in choriocarcinoma.

Objective: To analyse the efficacy of the floxuridine (FUDR)-containing regime (single agent or in combination) in the treatment of gestational trophoblastic tumor., Methods: Seventy-four patients with gestational trophoblastic tumors (GTT), 47 invasive mole and 27 choriocarcinoma, were treated with FUDR-containing regime. The clinical staging of the disease were: 33 cases of stage I, 3 cases of stage II, 31 cases of stage IIIa, 6 cases of stage IIIb, and 1 case of stage IV., Results: The cure rate of FUDR-containing regime in the treatment of GTT was 91.9% (68 out of 74 cases). Twenty-one out of these 74 patients showed drug resistant to 5-FU-containing or MTX-containing regime and were cured after they changed to the FUDR-containing regime. All 7 patients of advanced stage (> or = III b) got cured. The major adverse event of FUDR-containing regime was myelodepression and gastrointestinal toxicity: III-IV degree granulopenia 26%, III-IV thrombopenia 6.2%, III degree vomiting 57.1%, and III degree diarrhea 4.3%., Conclusion: FUDR-containing regime is efficient for the treatment of GTT, even for those with advanced stage or drug-resistant disease.

Objective: To investigate the efficacy and toxicity of methotrexate (MTX) give intravenously in the primary treatment of gestational trophoblastic tumor (GTT)., Methods: A total of 37 patients with low-risk GTT was primarily treated by single MTX in Women's Hospital, School of Medicine, Zhejiang University. Data on the patients' age, clinical stage, WHO classification criteria, antecedent pregnancy, presenting level of human chorionic gonadotropin, courses of chemotherapy required to achieve complete remission, and toxicity related to chemotherapy treatments were collected., Results: Thirty-seven patients with low-risk GTT totally received 137 cycles of MTX between Oct. 1999 and Sep. 2002, 34 patients (91.9%) achieved complete remission. Twenty-nine patients received multiple courses of MTX, complete remission was induced in 26 patients (89.7%). The complete response rates of I stage and III stage were 100.0% and 70.0% (P = 0.03) respectively in patients who were received multiple courses of MTX. However, eight patients received single course of chemotherapy, 7 patients achieved complete remission, and 1 achieved complete remission after another additional course of MTX was conducted. Grade III side effects (WHO criteria) only appeared in 7 courses (5.1%) during MTX treatment. Follow-up data showed that only one patient with single course of chemotherapy relapsed after 6 months., Conclusion: Single MTX chemotherapy may be effective and well tolerated for low-risk GTT.

Objective: To explore the risk of pregnancy in patients conceived within one year after successful chemotherapy for gestational trophoblastic tumor., Methods: 22 patients conceived within one year after chemotherapy were followed up and analysed about abnormal pregnant result, wastage rate and the time of interval between chemotherapy and pregnancy., Results: Among 22 cases, 9 cases were full term birth, 6 cases were wastage. The wastage rate was 27.3%. The wastage rate of these patients conceived within half a year was higher than one year (P < 0.05). 1 repeated hydatidiform mole and one post term choriocarcinoma occurred in 22 patients. They both were conceived within 5 months after chemotherapy., Conclusions: Preservation of fertility is feasible in patients suffering from choriocarcimona and invasive mole. But these patients should practise contraception at least half a year after chemotherapy, and it's better to advise patients to take contraception for one year.

Objective: To evaluate the response rate and toxicity of etopside, methotrexate, kengshengmycin, cyclophosphamide and vincristine (EMA/CO) regimen for women with chemorefractory gestational trophoblastic tumour., Methods: Fifty-one patients with chemorefractory gestational trophoblastic tumour were treated by EMA/CO regimen. Operative excision and (or) selective arterial infusion as adjuncts to chemotherapy were performed in a selected subset of patients. The response and toxicity were assessed after treatment., Results: Fifty-one patients received 352 cycles of the study regimen. The median number of courses for each patient was 6.9. Thirty-three cases (64.7%) achieved a complete remission while 14 patients (27.5%) had a partial remission, 4 cases showed nonresponse. Two (6.7%) of 30 complete responders developed recurrences. The main complications for EMA/CO chemotherapy were myelosuppression and gastrointestinal symptoms., Conclusion: The EMA/CO regimen is an effective treatment for chemorefractory gestational trophoblastic tumour, and the chemotherapeutic results can be further improved while combined with arterial infusion chemotherapy and surgery in the selected patients.

Objective: To evaluate the effectiveness, side effects and long term result of combination protocol of 5-fluorouracil (5-FU) and nitrocaphane (AT1258) on patients with malignant trophoblastic tumor., Methods: The chart and follow up data of 166 patients treated from 1979 to 1988 in Liaoning Province Tumor Hospital were reviewed. 136 invasive mole and 30 choriocarcinoma were treated by a 5-FU and AT1258 combined protocol. Their immediate treatment results, side effects and long-term follow-ups were retrospectively analysed., Results: The complete remission rate of invasion mole was 100.0% and choriocarcinoma 86.7%. The accumulative 5 and 10 year's survival rate for invasive mole were 100.0% and 99.3%, while 85.8% and 85.8% for choriocarcinoma. None of this group died of side effects or complication., Conclusion: 5-FU and AT1258 combination chemotherapy may be a protocol of choice in the treatment of malignant trophoblastic tumor.

Objective: In order to save the life of the patients with drug-resistant choriocarcinoma due to improper treatment, selective arterial catheterization was used., Methods: All the 71 cases were treated with systemic chemotherapy together with pelvic selective arterial chemotherapy. 5 of them had arterial chemotherapy plus arterial embolization for hemorrhage. In 13 patients who had lung metastasis, intraarterial injection of methotrexate (MTX) through bronchial arterial was added., Results: 55 of 71 (77.8%) achieved complete remission and 10 (14.1%) had partial remission. One patient failed to follow-up. 5 died of various causes during hospitalization. On Follow-up 12 had survived for more than 5 years with no signs of recurrence. 2 of them had childbirth after recovery., Conclusion: Systemic intravenous infusion chemotherapy in combination with arterial chemotherapy is useful for drug-resistant choriocarcinoma. In patients with intraperitoneal hemorrhage caused by tumor rupture, selective arterial embolization should be used as emergency treatment to effectively control the bleeding, in order that patients will have a chance for further chemotherapy.

Through catheter on uterine artery digital subtractive angiography (DSA) intraarterial infusion of chemotherapeutic agents for the treatment of malignant trophoblastic diseases can raise local drug concentration, improve therapeutic results and reduce general side-effects. But mural thrombosis, a possible complication of intra arterial catheterization, should not be overlooked. This study reports 2 cases of mural thrombosis complication in selective pelvic artery catheterization for chemotherapy. The incidence, relevant factors to its occurrence such as technique of catheterization and the duration of catheter retention, as well as measures of prevention and treatment of mural thrombosis are discussed together with review of literature. With regards to prevention of mural thrombosis, stress is being laid on the importance of the technique of catheterization. Preliminary comments on the problem of heparin administration as a preventive measure of mural thrombosis are made.

Among one hundred and eighteen cases of malignant trophoblastic tumor with pulmonary metastasis treated by chemotherapy, residual shadow on the X-ray films was seen in 18 (15%). Strict long follow-up observation of blood HCG and X-ray film indicated that the residual shadow spontaneously resorbed in 11 cases giving a survival of 3-5 years. The residual shadow showed no change in 1 case. Recurrence developed and repeated chemotherapy showed no response in 3. For the other 3, they were treated with lobectomy or local radiotherapy, 2 of whom survived for over 3 years and 1 died of mediastinal metastasis. The results suggest that the residual shadow can be resorbed with time in the majority of cases. Repeated Chemotherapy is undesirable.

From Jan. 1979 to Nov. 1987, 38 patients with invasive mole and 5 patients of choriocarcinoma were primarily treated with methotrexate and citrovorum factor (MTX-CF) rescue. Thirty-two patients had non-metastatic disease (stage I) and 11 had metastatic disease (stage IIA in 5 cases, stage IIB in 3 cases and stage IIIA in 3 cases). Complete remission was achieved in 28 (87.5%) of 32 patients with non-metastatic disease and in 9 (81.8%) of 11 patients with metastatic disease. Six patients with MTX-CF resistant tumors subsequently achieved complete remission with intravenous infusion of KSM and/or AT 1258. All patients were followed up periodically, 22 of them have been followed up for over 2 years, the longest duration of follow-up being 7 years. Seven of the 14 patients with preserved uterus became pregnant after recovery. All children grew up normally.