Comparing biweekly single-dose actinomycin D with multiday methotrexate therapy for low-risk gestational trophoblastic neoplasia (FIGO Score 0-4): study protocol for a prospective, multicentre, randomized trial.

BACKGROUND: Single-agent chemotherapy using methotrexate or actinomycin D is the first-line treatment for patients with low-risk gestational trophoblastic neoplasia. Various methotrexate-based and actinomycin D-based single-agent regimens can be used. However, there is insufficient evidence to determine the superior regimen. To guide doctors in selecting a single-agent chemotherapy regimen for patients with low-risk gestational trophoblastic neoplasia, we will compare two regimens. METHODS: We will conduct a multicentre, randomized, prospective clinical trial. Selected low-risk gestational trophoblastic neoplasia patients (FIGO score 0-4) will be randomized 1:1 to a biweekly single-dose actinomycin D group or a multiday methotrexate therapy group. The actinomycin D group will receive IV pulse actinomycin D (1.25 mg/m2) every 14 days, and the methotrexate group will receive methotrexate (50 mg) intramuscularly on days 1, 3, 5, and 7 (4 doses per cycle) and leucovorin (15 mg) intramuscularly on days 2, 4, 6, and 8. This process will be repeated every 14 days. The primary endpoints will include the complete remission rate by single-agent therapy and the overall complete remission rate. The secondary endpoints will include the duration needed to achieve complete remission after single-agent chemotherapy, number of courses needed to achieve complete remission after single-agent chemotherapy, incidence and severity of adverse effects, effects on menstrual conditions and ovarian function based on the anti-Mullerian hormone level, and patient-reported quality of life. DISCUSSION: Previous clinical trials comparing biweekly single-dose actinomycin D with multiday methotrexate therapy for treating low-risk gestational trophoblastic neoplasia patients failed to meet the expected case number. Through this multicentre study, the complete remission ratio and efficacy difference between biweekly single-dose actinomycin D and multiday methotrexate therapy will be obtained. This study will also provide the basis for formulating a preferred regimen for treating patients with low-risk gestational trophoblastic neoplasia. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04562558, Registered on 13 September 2020 (Protocol version 2020-9-24, version 1.0).

Combining serum peptide signatures with International Federation of Gynecology and Obstetrics (FIGO) risk score to predict the outcomes of patients with gestational trophoblastic neoplasia (GTN) after first-line chemotherapy.

Background: Gestational trophoblastic neoplasia (GTN) is a group of clinically rare tumors that develop in the uterus from placental tissue. Currently, its satisfactory curability derives from the timely and accurately classification and refined management for patients. This study aimed to discover biomarkers that could predict the outcomes of GTN patients after first-line chemotherapy. Methods: A total of 65 GTN patients were included in the study. Patients were divided into the good or poor outcome group and the clinical characteristics of the patients in the two groups were compared. Furthermore, the serum peptide profiles of all patients were uncovered by using weak cation exchange magnetic beads and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Feature peaks were identified by three machine learning algorithms and then models were constructed and compared using five machine learning methods. Additionally, liquid chromatography mass spectrometry was used to identify the feature peptides. Results: Multivariate logistic regression analysis showed that the International Federation of Gynecology and Obstetrics (FIGO) risk score was associated with poor outcomes. Eight feature peaks (m/z =1287, 2042, 2862, 2932, 2950, 3240, 3277 and 6626) were selected for model construction and validation by the three algorithms. Based on the panel combining FIGO risk score and peptide serum signatures, the neural network (nnet) model showed promising performance in both the training (AUC=0.9635) and validation (AUC=0.8788) cohorts. Peaks at m/z 2042, 2862, 2932, 3240 were identified as the partial sequences of transthyretin, fibrinogen alpha chain (FGA), beta-globin and FGA, respectively. Conclusion: We combined FIGO risk score and serum peptide signatures using the nnet method to construct the model which can accurately predict outcome of GTN patients after first-line chemotherapy. With this model, patients can be further classified and managed, and those with poor predicted outcomes can be given more attention for developing treatment failure.

The impact of pulmonary metastases on therapeutic response and prognosis in malignant gestational trophoblastic neoplasia patients: a retrospective cohort study.

AIM: The lung is the most common site of metastasis for gestational trophoblastic neoplasia (GTN). However, the level of influence of lung metastases on the prognosis of GTN and the degree to which lung metastases are considered in assessments of disease treatment options are unclear. Moreover, it is unclear which characteristics of lung metastases impact the disease. In this study, we evaluated the influence of lung metastases on the clinical course of GTN and identified lung imaging characteristics that impact treatment outcomes. METHODS: A retrospective cohort study was conducted on GTN patients treated at Peking Union Medical College Hospital between 2002 and 2018. The baseline characteristics, first-line treatment outcomes and final outcomes of patients with lung metastases (Group 1) and those without lung metastases (Group 2) were compared. RESULTS: The emergence of resistance occurred significantly more frequently in Group 1 (n = 994) than in Group 2 (n = 570) (19.52% versus 14.56%, p = 0.019), and the death rate was higher in Group 1 (0.91% versus 0%, p = 0.031). Among the patients treated with multi-agent chemotherapy, the rate of resistance and the number of treatment courses were significantly higher in Group 1 than in Group 2 (p = 0.002 and < 0.001, respectively). The lung imaging characteristics that impacted prognosis included the number of nodules, whether there were multiple nodules or a single nodule, and the number of nodules sized >1 cm. Multivariate analysis showed that a nodule measuring ≥1.8 cm was an independent risk factor for first-line treatment resistance and recurrence. CONCLUSION: Although pulmonary metastases do not affect overall survival in GTN patients, the presence of lung metastases before treatment is associated with increased risk of disease recurrence and resistance to first-line multidrug chemotherapy, especially when pulmonary nodules are larger than 1.8 cm. CLINICAL TRIAL REGISTRATION: N.A.

Reproductive outcomes after floxuridine-based regimens for gestational trophoblastic neoplasia: A retrospective cohort study in a national referral center in China.

OBJECTIVE: To analyze the reproductive outcomes of gestational trophoblastic neoplasia (GTN) patients who were cured only by floxuridine-based regimens. METHODS: This was a retrospective analysis of 464 patients who were treated with only floxuridine-based regimens at Peking Union Medical College Hospital between January 2002 and December 2013 and retained their reproductive ability. Their reproductive outcomes were analyzed. The factors affecting pregnancy intention were identified by logistic regression. RESULTS: Of the 464 patients (average age, 28.0 ± 5.7 years; median follow-up = 85 months), the livebirth rate was 72.2%, while the rates of spontaneous abortion, induced abortion and ectopic pregnancy were 9.2% (n = 41), 8.7% (n = 39) and 1.8% (n = 8), respectively. The GTN recurrence rate was 2.1%. The time from chemotherapy completion to first conception in the induced abortion group was significantly shorter than those in spontaneous abortion, full-term/premature, and ectopic pregnancy groups (P ≤ 0.001, <0.001, =0.015, respectively). The logistic analysis showed that the age at onset of GTN (OR = 0.899, 95% CI 0.851-0.951, P < 0.001), parity at onset of GTN (parity = 1, OR = 0.123, 95% CI 0.068-0.225, P < 0.001; parity = 2-3, OR = 0.058, 95% CI 0.014-0.232, P < 0.001) and interval from the index pregnancy to chemotherapy were independent factors affecting pregnancy intention. Among the 36 pregnancies occurring within 12 months postchemotherapy, only one choriocarcinoma occurred, and 20 culminated in induced abortions (55.6%). CONCLUSIONS: After floxuridine-based chemotherapy, the pregnancy rate of GTN patients after fertility-preserving treatment is comparable to that of the normal population. Pregnancy losses within one year after chemotherapy completion are mainly caused by induced abortion.

Pulmonary deportation of hydatidiform mole: a 12-year, single tertiary center experience in China.

BACKGROUND: Pulmonary deportation of hydatidiform mole is an exceedingly rare entity. The underlying mechanisms and proper management strategies remain unclear based on sporadic case reports over the past six decades. This study aimed to investigate the clinical features and rational treatment of patients with benign molar pregnancies with pulmonary deportation based on our experience. METHODS: Medical records of 20 cases of hydatidiform mole with pulmonary deportation were retrospectively reviewed at Peking Union Medical College Hospital from November 2006 to May 2019. The detailed information of all patients was recorded and analyzed. Patients were divided into different groups according to their characteristics and Mann-Whitney U test was used to compare the duration to achieve a normal ß-human chorionic gonadotrophin (ß-hCG) level after the first evacuation among groups. RESULTS: Initial pulmonary computed tomography scans showed suspected bilateral, left and right chest deportation of hydatidiform mole in 12, four, and four patients, respectively, with the maximum nodular diameter ranging from 0.6 to 1.2 cm. Ten patients achieved lesion resolution while the remaining ten patients achieved decreases in the size of their pulmonary lesions. The median duration to achieve a normal ß-hCG level after the first evacuation was 15.5 (13.0, 21.9) weeks. There was no significant difference in the duration to achieve a normal ß-hCG level after the first evacuation between two groups based on age (≥40 years vs. < 40 years: 15.8 [12.2, 21.5] weeks vs. 15.5 [12.9, 23.0] weeks, Z = 0.094, P = 0.925), type of antecedent mole (partial mole vs. complete mole: 15.2 [12.5, 27.4] weeks vs. 15.9 [12.9, 21.5] weeks, Z = 0.165, P = 0.869), distribution of pulmonary nodules (bilateral lungs vs. unilateral lung: 15.2 [12.8, 22.5] weeks vs. 15.9 [13.2, 22.2] weeks, Z = 0.386, P = 0.700), maximum size of pulmonary nodules (>0.5 cm vs. ≤0.5 cm: 13.0 [11.3, 17.2] weeks vs. 16.0 [14.5, 23.8] weeks, Z = 1.815, P = 0.070), and number of uterine evacuations (once vs. twice or three times: 15.0 [13.0, 16.3] weeks vs. 16.0 [12.8, 23.9] weeks, Z = 0.832, P = 0.405). The post-molar cohort was followed up for 17 to 139 months, and no gestational trophoblastic neoplasia was observed. CONCLUSIONS: No surgeries other than uterine evacuation and no chemotherapy regimens are recommended for such patients if they achieve satisfactory decreases in the level of hCG and gradual decrease or disappearance of pulmonary deportation nodules. Patients should be informed about the necessity of long-term follow-up. More collaborative international studies on this exceedingly rare condition may guide decisions regarding optimal management strategies.

Evaluation and suggestions for improving the FIGO 2000 staging criteria for gestational trophoblastic neoplasia: A ten-year review of 1420 patients.

BACKGROUND: To re-evaluate the efficacy of the prognostic factors currently employed in the treatment of malignant gestational trophoblastic neoplasia. METHODS: Clinical data from the Gestational Trophoblastic Disease (GTD) Center at Peking Union Medical Hospital (PUMCH) collected between January 2002 and December 2013 were retrospectively analyzed. Univariate and multivariate analyses of prognostic factors were performed using the Cox proportional hazards model. A new hazard ratio (HR)-based prognostic scoring scale was established and compared with the original scoring system. RESULTS: In total, 1420 cases were included in the study (median follow-up=40months, overall complete remission (CR) rate=95.8%, relapse rate=7.1%, mortality rate=5.5%, median disease-free survival (DFS)=36months). Low-risk (0-6 points) and high-risk (≥6 points) patients exhibited CR rates of 99.8% (915/917) and 88.5% (445/503) and mortality rates of 0.3% and 15.1% (P<0.001), respectively. Univariate and multivariate analyses showed that age, pretreatment serum levels of human chorionic gonadotropin beta-subunit (ß-hCG) and maximum tumor diameter were not independent prognostic risk factors. Antecedent pregnancy, the interval from the index pregnancy, the number of metastases and a history of failed chemotherapy treatments were independent prognostic risk factors. By modifying the scoring system based on the variables identified in a Cox analysis, we significantly increased the area under the receiver operating characteristics (ROC) curve. CONCLUSION: Though effective, the accuracy of the International Federation of Gynecology and Obstetrics (FIGO) 2000 Trophoblastic Neoplasia Staging System requires improvement. Irrelevant prognostic factors should be removed, and the weights of other factors should be adjusted appropriately.

Combination chemotherapy regimen with floxuridine, dactinomycin, etoposide, and vincristine as primary treatment for gestational trophoblastic neoplasia.

OBJECTIVE: To evaluate the combination chemotherapy regimen with floxuridine, dactinomycin, etoposide, and vincristine (FAEV) as primary treatment for gestational trophoblastic neoplasia (GTN). METHODS: Clinical data and outcome of the patients with GTN from 1 January 2004 to 31 December 2009 were retrospectively reviewed. Totally 38 eligible patients had received at least one cycle of FAEV chemotherapy as primary treatment. The primary end points were response rate and toxicity of FAEV regimen. RESULTS: Totally 38 patients and 205 cycles of FAEV chemotherapy were included. Twenty-eight of these patients (73.6%) achieved serologic complete remission (SCR). Regimens were changed in 10 patients because of 5 with no response and 5 with intolerable toxicity. The most serious adverse events were greater than or equal to grade 3 neutropenia (31.6%), febrile neutropenia (7.9%), and greater than or equal to grade 3 thrombocytopenia (5.3%). During the follow-up, none relapsed. CONCLUSION: FAEV is an effective regimen with manageable toxicity for patients with GTN as primary treatment, especially for patients with non-metastatic low or high risk GTN.

Clinical analysis of 13 males with primary choriocarcinoma and review of the literature.

OBJECTIVE: To analyze the management and prognosis of primary choriocarcinoma (PCC) in male patients. METHODS: The clinical records of males with PCC who were treated at Peking Union Medical College Hospital between 1990 and 2012 were analyzed retrospectively. The literature regarding this clinical condition was also reviewed. RESULTS: The median survival interval of the 13 patients treated at Peking Union Medical College Hospital was 54 months (range, 6-115 months), and the 1- and 3-year survival rates were 53.8% and 43.1%, respectively. All patients were treated with surgery; 12 were treated with combined chemotherapy. After including 100 cases found in the literature, for a total of 113 patients, the median survival interval was 10 months (range, 6.4-13.6 months). The testis was the most common primary site (36.2%). Most patients (70.9%) had metastatic lesions at diagnosis. Univariate and multivariate analyses revealed that longer median overall survival was significantly associated with patient age <34 years old (48 months vs 10 months, odds ratio [OR] =0.47, P=0.029), the presence of other histological components (54 months vs 11 months, OR =0.54, P=0.011), and combined chemotherapy and surgical treatments (14 months vs 2.5 months, OR =0.18, P=0.002). CONCLUSION: PCC is an extremely rare disease among men, and its prognosis is much worse than that of gestational choriocarcinoma. The complete resection of the primary site and metastases followed by chemotherapy seems to provide patients with the best chance at survival. Furthermore, additional chemotherapy cycles might facilitate better progress.

Preoperative neutrophil-lymphocyte and platelet-lymphocyte ratios as independent predictors of cervical stromal involvement in surgically treated endometrioid adenocarcinoma.

BACKGROUND: The purpose of this study was to evaluate the relationship between preoperative inflammatory markers (neutrophil-lymphocyte ratio and platelet-lymphocyte ratio) and cervical stromal involvement in patients with endometrioid adenocarcinoma. METHODS: We studied 318 patients with endometrioid adenocarcinoma who underwent comprehensive surgical staging. We used univariate and multivariate analyses of cervical stromal involvement and receiver-operating curves to calculate optimal cutoff values for neutrophil-lymphocyte and platelet-lymphocyte ratios to predict cervical stromal involvement. RESULTS: The presence of cervical stromal involvement was associated with neutrophil-lymphocyte ratio and platelet-lymphocyte ratio (P = 0.009 and P = 0.031, respectively). Multivariate analysis showed that higher neutrophil-lymphocyte and platelet-lymphocyte ratios independently predicted cervical stromal involvement (odds ratio 3.10, 95% confidence interval 1.10-8.76, P = 0.032, and odds ratio 5.27, 95% confidence interval 1.94-14.35, P = 0.001, respectively). At a threshold of 2.01, the neutrophil-lymphocyte ratio was 71.0% sensitive and 63.8% specific for stromal involvement; at a 172.24 threshold, the platelet-lymphocyte ratio was 48.4% sensitive and 88.9% specific. CONCLUSION: Preoperative neutrophil-lymphocyte and platelet-lymphocyte ratios can help identify the risk of cervical stromal involvement in patients with endometrial cancer. Evaluating these ratios may help select patients who should be particularly watched and tested for cervical stromal involvement.

[Role of endoplasmic reticulum protein folding molecular chaperones in floxuridine-resistance choriocarcinoma JeG-3/FUDRA cell line].

OBJECTIVE: To investigate changes of protein expression profiles between human choriocarcinoma JeG-3 cell line and its floxuridine (FUDR)-resistant sub-line. METHODS: The differentially expressed proteins were identified by using two dimension difference gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) approaches. Gene ontology (GO) analysis and Pathway analysis were used to screen the candidate proteins. The levels of the proteins in chemo-resistant sub-lines were validated by western blot. Ribonucleic acid interference (RNAi) was used to knockdown the expression of calreticulin (CALR) and (or) protein disulfide-isomerase A3 (PDIA3) respectively. RESULTS: Forty-six proteins spots were found to be significantly different in spot intensity by statistical analysis between chemo-resistance sub-line and parent cell line, of which 31 proteins were identified by MALDI-TOF-MS. Comparing to the parent cell lines, three endoplasmic reticulum (ER) protein folding molecular chaperones: CALR, PDIA3 and 78 000 glucose-regulated protein (GRP78) screened out were increased significantly in floxuridine-resistant sub-line and were verified by western blot. The resistance index decreased by knockdown the CALR and/or PDIA3 expression in FUDR-resistant sub-line 76.3% (36.7 ± 2.0 vs. 8.7 ± 3.1, P < 0.05) and 51.4% (36.7 ± 2.0 vs. 17.8 ± 1.2, P < 0.05) respectively. CONCLUSION: These ER protein folding molecular chaperones, CALR, PDIA3 and GRP78, may involved in the mechanism of FUDR-resistance choriocarcinoma.

[Effects of pre-chemotherapy hemoglobin and platelet levels in patients with stage Ib2-IIb cervical cancer treated with neoadjuvant chemotherapy followed by radical hysterectomy].

OBJECTIVE: To investigate the role of pre-chemotherapy hemoglobin and platelet levels in the effect of chemotherapy and prognostic outcome in patients with International Federation of Gynecology and Obstetrics (FIGO) stage Ib2-IIb cervical cancer treated with neoadjuvant chemotherapy followed by radical hysterectomy. METHODS: From January 1999 to December 2010, 111 patients with FIGO stage Ib2-IIb who underwent chemosurgical treatment at the department of obstetrics and gynecology in Peking Union Medical College Hospital were reviewed. The median age of patients was 42 years (range: 21 - 68 years). The median level of prechemotherapy hemoglobin and platelet levels was 127 g/L and 266 × 10(9)/L, respectively. Chemotherapy response was evaluated according to the WHO criteria, including complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). Patients who achieved CR or PR were defined as responder. Rates of clinical response were compared with the clinical-pathological variables using chi-square test. Multiple logistic regression was carried out to evaluate the relationship among the probability of achieving an optimal clinical response and the variables. The log-rank test was used to compare the homogeneity of progression-free survival and overall survival functions across strata defined by categories of prognostic variables. The Cox proportional hazard model was used to assess the significance of potential prognostic factors for progression-free survival and overall survival. RESULTS: All patients received one to three cycles of chemotherapy. After the neoadjuvant chemotherapy, 9 patients achieved CR, 77 patients PR, 23 patients SD, 2 patients PD. The overall response rate was 77.5% (86/111). By univariate analysis, the clinical response rate was associated with tumor grade (P = 0.026), deep cervical stromal invasion (P = 0.029) and positive lymph nodes (P = 0.048). By multiple logistic regression, deep cervical stromal invasion (P = 0.015) and positive lymph nodes (P = 0.031) were independent predictors of optimal clinical response. By log-rank test, 5-year overall survival rate and 5-year progression-free survival rate were associated with lymph nodes metastases status and lymphovascular invasion (P = 0.000), but not with hemoglobin and platelet levels (P > 0.05). By Cox regression model, lymph nodes metastases status and lymph-vascular space involvement (P < 0.01) were independently prognostic factors of 5-year overall survival rate and 5-year progression-free survival rate. CONCLUSION: Pretreatment hemoglobin and platelet levels were neither predictors of clinical response to chemotherapy nor prognostic factors.

Treatment of respiratory failure in metastatic pulmonary choriocarcinoma: an experience at Peking Union Medical College Hospital, China.

BACKGROUND: Respiratory failure caused by metastatic pulmonary choriocarcinoma usually develops rapidly and is associated with a high mortality. The clinical management strategy is important in choriocarcinoma patients with acute respiratory failure. The objective of this study was to evaluate the clinical characteristics, treatment outcome and potential risk factors in patients with acute respiratory failure from metastatic pulmonary choriocarcinoma. METHODS: Sixteen patients with acute respiratory failure from pulmonary metastases choriocarcinoma were enrolled and treated at Peking Union Medical College Hospital from 1995 to 2010. Clinical characteristics, causes of pulmonary failure, treatment profiles and outcomes were analyzed retrospectively. RESULTS: The presence of respiratory infection or hemorrhage was associated with acute respiratory failure in patients with metastatic choriocarcinoma. Fifteen (93.8%) patients presented with pulmonary infection, 8 (50.0%) patients with pulmonary hemorrhage. All patients were treated with face mask or mechanical ventilation. Fourteen (87.5%) patients received initial chemotherapy at a low dosage or with modified regimens, with a median of 2 cycles (range 1 to 4). Seven patients achieved a complete remission (CR), two had a partial remission. Six CR patients remained alive with a median follow-up of 59 months (range 16 to 120). Seven patients developed progressive diseases and subsequently died. CONCLUSIONS: Respiratory infection and hemorrhage were associated with acute respiratory failure in metastatic pulmonary choriocarcinoma. The initial administration of gentle chemotherapy regimens, accompanied with mechanical ventilation, is feasible and effective in attenuating respiratory failure in patients with metastatic pulmonary choriocarcinoma.

[Clinical analysis of 15 cases of malignant ovarian germ cell tumors with lung metastasis].

OBJECTIVE: To investigate the clinical characteristics, diagnosis, treatment and prognosis of malignant ovarian germ cell tumors (MOGCT) with lung metastasis. METHODS: Fifteen patients of MOGCT with lung metastasis treated in Peking Union Medical College Hospital from Jan. 1982 to Dec. 2010 was retrospectively analyzed. RESULTS: (1) Clinical characteristics: the average onset age of these 15 patients is (23 ± 11) years old (6 - 48 years). The majority of these patients presented with abdominal pain (8/15) or irregular vaginal bleeding (4/15) as their initial symptoms. The primary tumor located in the left ovary in 8 cases, right ovary in 6 cases, and both sides in only 1 case. Metastatic lesions were confined to the lung in 12 patients, while the other 3 patients were found to have multi-site distant metastasis. (2) DIAGNOSIS:all 15 cases included 9 pure non-gestational ovarian choriocarcinoma (NGOC), 3 MOGCT containing choriocarcinoma component (one mature teratoma with choriocarcinoma component, one endodermal sinus tumor with embryonal carcinoma and choriocarcinoma components, one choriocarcinoma with dysgerminoma component), 2 embryonal carcinoma, one immature teratoma. Only one patient in these 15 cases was correctly diagnosed before surgery. (3) Time of lung metastasis:of 12 MOGCT with choriocarcinoma component, 11 patients were found to have lung metastasis in the course of their primary treatment, only 1 had lung metastasis 2 months after the synthetic treatment finished. Three MOGCT patients without choriocarcinoma component were all found to have lung metastasis when tumor relapsed in the advanced stages of the disease. (4) TREATMENT:all 15 patients received multi-agent chemotherapy combined with surgery. The mean courses of chemotherapy for these patients were 16 courses (5 - 43 courses). (5) PROGNOSIS: of these 15 cases, complete remission was obtained in 10 patients of NGOC or mixed ovarian germ cell tumors with choriocarcinoma component, 3 patients (one NGOC, one endodermal carcinoma and one immature teratoma, respectively) died in the course of treatment as result of tumor progression, 2 progressed cases (one NGOC and one endodermal carcinoma respectively) abandoning therapy were lost to follow up. CONCLUSIONS: MOGCT with lung metastasis are more often to found in NGOC patients. These patients could obtain high complete remission rate after standard multi-agent chemotherapy combined with surgery. The prognosis of MOGCT with lung metastasis containing choriocarcinoma component are better than that of those without containing choriocarcinoma component.

[Analysis of prophylactic chemotherapy outcome and clinical characteristics in patients of high-risk hydatidiform mole].

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 ß-hCG in two groups were 469 144 U/L and 768 044 U/L respectively, and median days needed for ß-hCG declining to normal (≤ 2 U/L) at the first time were 71 and 120 days respectively, which were both significantly different between two groups. Analyzed with receiver operating characteristics (ROC), the level of serum ß-hCG could be a predictor for prognosis. Choosing 750,000 U/L as the cut-off value, we could expect the serum ß-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 ß-hCG reached 750 000 U/L so as to reduce therapy duration and prevent relevant chemoresistance.

[Factors associated with quality of life in survivors of gestational trophoblastic neoplasm after chemotherapy].

OBJECTIVE: To measure the quality of life (QoL) of gestational trophoblastic neoplasia (GTN) survivors after chemotherapy by using a self-invented scale, and to explore the factors associated with QoL. METHODS: The design of questionnaire was based on a series of internationally valid QoL scales, which was tested by epidemiology and showed good reliability and validity. A total of 100 survivors of GTN patients from Peking Union Medical College Hospital participated in this survey from December 2008 to May 2009. RESULTS: Patients with disease-free more than three months after chemotherapy enjoys a good QoL, while only 16% (16/100) of survivors feel general overall QoL, but no one feels bad QoL. As refer to sexual function, more than half of these patients (70%, 70/100) satisfied with their sexual life, while there were still 47% (47/100) and 45% (45/100) of the patients complaining of decreased sexual desire and dryness of vagina. 66% (66/100) of the GTN survivors expressed depression, and 50% (50/100) of patients complained anxiety, which were potential factors influencing QoL of GTN survivors. Relevant analysis explored the possible predictors of QoL for GTN patients, including physical function (r = 0.609, P < 0.01), sexual function (r = 0.473, P < 0.01), and social psychology (r = 0.294, P < 0.01). CONCLUSIONS: GTN survivors have an overall good QoL after chemotherapy, the possible predictors of QoL for GTN patients include physical function, sexual function and social psychology. The sexual dysfunctions mostly present with short of sexual desire and dryness of vagina. Fear of recurrence may be a potential factor influencing QoL a long term after remission.

[Genetic genesis of choriocarcinoma].

OBJECTIVE: To distinguish choriocarcinoma from gestational or non-gestational choriocarcinoma and also identify the causative pregnancy of gestational choriocarcinoma by the genetic origin through molecular genetic analysis. METHODS: Twelve patients with choriocarcinoma, who had experienced surgery prior to chemotherapy were enrolled in this study. All 12 cases were diagnosed pathologically as choriocarcinoma. Peripheral venous blood samples and formalin-fixed paraffin-embedded blocks of choriocarcinoma tissue microdissected from haematoxylin and eosin-stained sections of tissue by microdissection method were available from the patient and (or) her husband. DNA was then prepared from the couples' blood samples and choriocarcinoma tissue by using standard techniques. PCR amplification and fluorescent microsatellite genotyping were performed by using DNA from the couples and captured choriocarcinoma tissues. The genetic contributions to the choriocarcinoma tissue were determined by comparing the fragments of genes from the choriocarcinoma tissue to those from blood samples of the couples. RESULTS: The primary lesion was ovary in 7 cases, but only 4 of them had the maternal contribution, indicating a non-gestational origin; the other three were gestational choriocarcinoma. The primary lesion was uterus in 5 cases, which were all gestational choriocarcinoma confirmed by genetic analyses. The causative pregnancies of the 8 cases with gestational choriocarcinoma were identified as androgenetic complete hydatidiform mole (AnCHM) in six cases and normal pregnancies in two cases, respectively. CONCLUSION: Microsatellite polymorphism analysis is a molecular approach for distinguishing the non-gestational choriocarcinoma from the gestational one, and also be used to identify the causative pregnancy of gestational choriocarcinoma.

[Mullerian adenosarcoma of the uterus: A clinicopathologic analysis of 9 cases].

OBJECTIVE: To investigate the clinicopathologic features, diagnosis, treatment and prognosis of uterine mullerian adenosarcoma. METHODS: The clinicopathological data of 9 cases of uterine mullerian adenosarcoma in PUMC hospital from January 2003 to February 2009 were retrospectively analyzed. RESULTS: There were 6 uterine endometrial adenosarcomas and 3 cervical adenosarcomas. The main clinical manifestations were abnormal vaginal bleeding and pelvic pain. Physical examination showed cervical/vaginal mass, enlarged uterus or pelvic mass. The adenosarcoma was characterized by benign or atypical-appearing neoplastic glands within a sarcomatous stroma. This stroma could appear as periglandular cuffs or intraglandular polypoid projections of increased cellular structure. The primary diagnostic rate was 66.7% and the most common clinical stage was stage I (7/9). All patients received surgical treatment and seven had postoperative chemotherapy, radiotherapy or hormone therapy. Conservation of unilateral ovary or bilateral ovaries was performed in 5 cases. Three patients underwent local excision, which resulted in the preservation of reproductive function. During the follow-up, 2 cases of uterine endometrial adenosarcoma recurred. One patient of clinical stage III containing sarcomatous overgrowth died from recurrence 13 months after surgery. The other one recurred 2 years after local excision of the tumor in the uterine cavity and she remained healthy since hysterectomy. CONCLUSION: Uterine mullerian adenosarcoma is a rare tumor without specific clinical symptoms and signs. The diagnosis depends on pathomorphologic examination. The tumors show low malignant potential and the vast majority are at early stage. Surgical excision is the main treatment strategy with a good prognosis in the early stage disease with complete removal of tumors. The prognosis is poor in advanced adenosarcoma with sarcomatous overgrowth. Due to the relatively high rate of recurrence, long-term follow-up is recommended.

Clinical analysis of 21 cases of nongestational ovarian choriocarcinoma.

INTRODUCTION: The objective of the study was to investigate the clinical characters, diagnosis, treatment, and prognosis of nongestational ovarian choriocarcinoma. METHODS: A retrospective analysis was done on 21 patients with nongestational ovarian choriocarcinoma treated in Peking Union Medical College Hospital from January 1985 to October 2008. All patients' conditions were diagnosed by histopathologic examination; in 3 of them, the diagnosis was confirmed by DNA polymorphism analysis at 12 short tandem repeat loci. RESULTS: Correct diagnosis was achieved in only 3 patients before initial treatment. All patients received standard multiple-drug combined chemotherapy and underwent an operation. The mean number of chemotherapy courses for each patient was 10. Of the 21 patients, 16 achieved complete remission, and 4 obtained partial remission; 1 died. In a median follow-up of 71.4 months, the 5-year overall survival rate was 79.4%. CONCLUSIONS: The early diagnosis of nongestational ovarian choriocarcinoma is expected to be improved. DNA polymorphism analysis is a useful tool in determining the origin of ovarian choriocarcinoma. The prognosis is optimistic if managed with standard multiple-drug chemotherapy combined with surgical treatment.