Objective:To investigate the therapeutic effect of programmed cell death receptor 1 (PD-1) inhibitor in drug-resistant recurrent gestational trophoblastic neoplasia (GTN).Methods:Clinicopathological features, previous treatments, PD-1 inhibitor treatment and prognosis of 8 patients with drug-resistant recurrent GTN treated with PD-1 inhibitor pembrolizumab， in Peking Union Medical College Hospital of Chinese Academy of Medical Sciences from August 2018 to June 2019 were collected and retrospectively analyzed.Results:(1) Clinicopathological features: the average age of onset of 8 GTN patients was 32.9 years old (31-39 years old); pathological types: choriocarcinoma in 7 cases, epithelioid trophoblastic tumor in 1 case. International Federation of Gynecology and Obstetrics (FIGO) stages: stage Ⅲ in 5 cases, stage Ⅳ in 3 cases; FIGO score: 4 patients with 7-12 points (high-risk group) and 4 patients with ≥13 points (ultra high-risk group). All the 8 patients had lung metastasis, 2 patients with brain metastasis, 1 patient with kidney and 1 patient with intestinal metastasis. (2) Previous treatments: ① Chemotherapy: 8 patients with GTN received an average of 21.1 courses (5-30 courses) of chemotherapy; the main route was systemic intravenous chemotherapy. One patient received intrathecal methotrexate chemotherapy due to brain metastasis. ② Surgery: 7 of 8 patients with GTN received surgical treatment, including 5 cases of pelvic surgury, 6 cases of pulmonary lobectomy and 1 case of right hemicolectomy. ③ Radiotherapy: 2 of 8 patients with GTN received radiotherapy, among which 1 patient received radiotherapy for lung for 8 times due to lung metastasis, and the other one received radiotherapy for lung, right sacroiliac joint and skull for a total of 22 times. (3) PD-1 inhibitor treatment: 8 patients with GTN received PD-1 inhibitor treatment with a mean course of 9 (2-12 courses). Six patients appeared Ⅰ-Ⅱ grade of immune related adverse events (AE), and no severe AE occurred. (4) Prognosis: after 2-3 courses of PD-1 inhibitor treatment, serum β-hCG level came to normalization in 4 patients. They were followed up for 2-7 months without any recurrence after 0-9 courses of consolidation treatment. One patient received 12 courses of PD-1 inhibitor treatment. The serum β-hCG level normalized after the 6th courses but increased 1 months later, and then received bevacizumab treatment due to the progression of the disease. The remaining 3 patients received other chemotherapy regiments due to disease progression during PD-1 inhibitor treatment.Conclusions:PD-1 could be used as a remedial treatment for drug-resistant recurrent GTN, with a high effective rate and relatively mild AE. However, more cases need to be accumulated clinically and efficacy should be comprehensively evaluated in combination with pathology and immunohistochemical examination.

Objective To summarize and analyze the clinical outcomes of gestational trophoblastic neoplasia (GTN) patients receiving primary treatment at Peking Union Medical College Hospital from 1985 to 2015,and investigate the changes in treatment efficacy between the first and the second 15 years.Methods Clinical data of GTN patient receiving primary chemotherapy at Peking Union Medical College Hospital from January 1985 to December 2015 were retrospectively analyzed.It further compared the therapeutic results and chemotherapy cycles given to GTN patients,according to International Federation of Gynecology and Obstetrics (FIGO,2000) prognostic score system,who were classified to different stages and low-or high-risk groups.Results In total,1 711 GTN patients were included in this study.Comparing the 1985-2000 group and the 2001-2015 group,the results showed that:(1) while the overall complete remission (CR) rate was 93.7％ (1 603/1 711),the CR rate of 2001-2015 group was significantly higher than that of 1985-2000 group [98.4％ (1 155/1 174) vs 83.4％ (448/537),x2=139.353,P＜0.01].This difference was significant between stage Ⅲ and Ⅳ patients,but nonexistent between stage Ⅰ and Ⅱ patients,including low-and high-risk groups.(2) The relapse rate of patients who had been in CR was 2.7％ (43/1 603),with no significant differences between the groups of 1985-2001 and 2001-2015 [3.6％ (16/448) vs 2.3％ (27/1 155),x2=6.867,P=0.142].(3) The overall mortality rate was 2.6％ (44/1 711),which significantly decreased in 2001-2015 group compared to 1985-2000 group [1.6％ (19/1 174) vs 4.7％ (25/537),x2=13.830,P＜0.01].This difference appeared only in high-risk patients with stage Ⅲ disease (x2=9.505,P＜0.01).(4) Fluorouracil was gradually replaced by floxridine in chemotherapy regimens.The total cycles of chemotherapy regimens given to low-risk patients with stage Ⅲ disease significantly decreased in 2001-2015 group,but no statistical difference was shown with patients at other stages.Moreover,the cycles of consolidation treatment were significantly reduced in patients with stage Ⅲ patients.Conclusions GTN patients could obtain satisfactory curative results after appropriate and standard treatment.Peking Union Medical College Hospital has achieved better curative effect in the latest 15 years than before.

Objective Using a questionnaire to evaluate different regimens of chemotherapy on ovarian function and quality of life of patients with gestational trophoblastic neoplasia (GTN).Methods At least 6 months after completion of chemotherapy,200 patients with GTN treated in Peking Union Medical College Hospital from January 2010 to June 2017 were randomly selected to fill up the questionnaire.The questionnaire items were included the patient's menstrual cycles,sexual life,gestational issues and common health.The patients were divided into 3 groups by chemotherapy regimens:actinomycin D (Act-D) group,floxuridine + Act-D + vincristine (FAV) or floxuridine + Act-D + etoposide + vincristine (FAEV) group (FAV-FAEV group),and etoposide + methotrexate + Act-D (EMA)/vincristine + cyclophosphamide (CO) or EMA/ etoposide + cisplatin (EP) group (EMA/CO-EMA/EP group).Chi-square test was used with a significance level of P-value less than 0.05.Results One hundred and seventy-three (86.5％,173/200) of the patients completed the questionnaire.Forty three point two percent (43.2％,19/44) in the EMA/CO-EMA/EP group had a normal menstrual cycle,which were significantly lower than those of Act-D group (84.6％,22/26) and FAV-FAEV group (71.2％,37/52;all P＜O.05).Amenorrhea rate was also significantly higher in EMA/CO-EMA/EP group (25.0％,11/44) than in Act-D group(0) and FAV-FAEV group (17.3％,9/52;all P＜0.05).The sexual life parameters were comparable among 3 groups.Ten out of thirty-two patients conceived after chemotherapy,2 had miscarriages and 8 had full-term delivery of healthy babies.The common health and labor capacity were significantly decreased after chemotherapy (all P＜0.05).Conclusions EMA/CO or EMA/EP regimen have a worse impact on ovarian function than Act-D and FAV or FAEV regimen.Gynecologic oncologist should be concerned about the ovarian function and quality of life of GTN patients.

Objective To discuss the effects of prophylactic chemotherapy on the outcomes and prognosis of invasive mole patients.Methods One hundred and fifteen invasive mole (IM) patients older than 40 years were registered in Peking Union Medical Collage Hospital.Eleven of them were treated with prophylactic chemotherapy before diagnosed as IM prophylactic chemotherapy group,while the other 104 cases received therapeutic chemotherapy after diagnosed as IM (non-prophylactic chemotherapy group).The general clinical data (including age,clinical stage,risk factor score),treatment,outcomes and relapse of patients were retrospectively compared between two groups.Results (1) The age of prophylactic chemotherapy group and non-prophylactic chemotherapy group were (47±5) versus (46±4) years old.Ratio of clinical stage Ⅰ-Ⅱ were 3/11 versus 29.8％ (31/104),clinical stage Ⅲ-Ⅳ were 8/11 versus 70.2％ (73/104).Ratio of risk factor score 0-6 were 11/11 versus 84.6％ (88/104),risk factor score ＞6 were 0 versus 15.4％(16/104).There were no significant statistical differences between two groups in age,clinical stage or risk factor score (all P＞0.05).(2) Treatment:the total chemotherapy courses between prophylactic chemotherapy group and non-prophylactic chemotherapy group (median 7 versus 5) were significantly different (Z=3.071,P=0.002).There were no significant statistical differences between two groups in the chemotherapy courses until negative conversion of β-hCG,consolidation chemotherapy courses,total therapeutic chemotherapy courses or ratio of hysterectomy (all P＞0.05).(3) Outcomes and relapse:between the prophylactic chemotherapy group and the non-prophylactic chemotherapy group,the complete remission rate were 11/11 versus 98.1％(102/104),the relapse rate were 0 versus 1.0％(1/102).There were no significant difference between the two groups in outcomes or relapse rate (P＞0.05).Conclusions Prophylactic chemotherapy does not substantially benefit the IM patients older than 40 years.Prophylactic chemotherapy may not significantly improve patients' prognosis,in which increased sample size is required in further study.

Objective To evaluate the value of laparoscopic surgery in the diagnosis of suspected gestational trophoblastic neoplasia (GTN) cases with uterine mass.Methods The clinical characteristics of patients underwent laparoscopic surgery for a suspected diagnosis of GTN with uterine mass in Peking Union Medical College Hospital from November 2009 to November 2014 were retrospectively reviewed and analyzed.GTN and other pregnant-related disease were definitely diagnosed by pathological findings.The prognoses of the GTN cases were also investigated.Results Sixty-two patients with a suspected diagnosis of GTN with uterine mass were studied.Among them,17 cases were definitely diagnosed as GTN,including 8 choriocarcinoma,5 invasive mole and 4 placental site trophoblastic tumor(PSTT).The other 45 cases were diagnosed as benign pregnancy-related diseases,including 29 cornual pregnancy,6 cesarean scar pregnancy,5 placenta accreta,4 intramural uterine pregnancy and 1 exaggerated placental site.There were no significantly differences between the two groups in average age,preoperative value or tendency of β-hCG,and location or size of lesions (P＞0.05).More GTN patients showed a history of hydatidiform mole [5/17 vs 4％ (2/45),P＞0.05],and more patients with benign pregnancy-related disease showed a history of cesarean section [38％ (17/45) vs 1/17,P＞0.05].No serious perioperative complication was found in these patients received laparoscopic surgery.All GTN patients achieved complete remission by chemotherapy later.Except for 1 case loss,no recurrence was found in 11 low-risk stage Ⅰ cases with an average follow-up period of 11-66 months,1 high-risk stage Ⅰ case with a follow-up period of 61 months and 4 cases PSTT with a follow-up period of 13-66 months.Conclusions There were some atypical GTN cases with uterine mass,which were difficult to be differentiated from benign pregnancy-related diseases according to the clinical characteristics.Laparoscopic surgery with a pathologic diagnosis could be an essential way with efficiency and safety.

Objective To analyze the treatment and prognosis of patients with gestational trophoblastic neoplasia with urinary system and adrenal glands metastasis.Methods The treatment and prognoses of 32 patients with gestational trophoblastic neoplasia with urinary system and adrenal glands metastasis from Dec.1990 to Dec.2010 at Peking Union Medical College Hospital,Chinese Academy of Medical Sciences were respectively reviewed.Results Treatment methods:all 32 patients received 9 courses(in average) of a multi-drug chemotherapy in our hospital (range 1-24 coures).Among them,3 patients with bladder metastasis received intravesical chemotherapy of fluorouracil.9 patients received surgical treatments in other hospital and 15 patients received surgical treatments while undergoing chemotherapy in our hospital.Treatment results:after the treatments,of the 32 patients,21 (66％) patients achieved complete remission,3(9％) exhibited partial remission and 8 (25％) progressed.Seven patients with renal metastasis achieved complete remission.Two patients with adrenal glands metastasis achieved complete remission.Nine patients with urinary bladder metastasis achieved complete remission.Seven patients with ureters metastasis achieved complete remission.Two (10％) of 21 patients with complete remission relapsed.Conclusions Multidrug and muhiroute chemotherapy is the main strategy for patients with gestational trophoblastic neoplasia with urinary system and adrenal glands metastasis.The prognoses of patients with renal or adrenal glands metastasis are much worse than those in patients with bladder and ureters metastasis because of concomitant multiogran metastasis.Adequate attention should be given to patients with renal or adrenal glands metastasis.Individual treatment,assisted by surgery when necessary,may be carried out for these patients to achieve a better outcome.

Objective To study the clinical features,differential diagnosis and treatment of caesarean scar pregnancy (CSP) with sonographic mass.Methods A retrospective analysis was performed on 39 patients of CSP with sonographic mass undergoing treatment in Peking Union Medical College Hospital from 2005 to 2012.14 cases with misdiagnosis of gestational trophoblastic neoplasm,among 4 cases were administered by chemotherapy with methotrexate (MTX),cisplatin,fluorouracil (5-FU) and dactinomycin.According to treatment methods,39 cases were divided into five groups: 3 cases in methotrexate,16 cases in dilation and curettage,15 cases in excision of CSP lesion via laparoscopy,6 cases in excision of CSP lesion via laparotomy,and 4 cases in transabdominal hysterectomy (TAH).Results (1)Clinical characteristics: the mean age was (33 ± 5) years old.Five patients had undergone two prior caesarean sections.The median interval from the last caesarean delivery to CSP was 4 years.Thirty-five cases presented vaginal bleeding or abnormal serum β-hCG level from 5 cases with medical abortion,9 cases with artificial abortion and 21 cases with dilation and curettage.The sonography showed cystic-solid or solid mass with mixed echoes in the lower segment of anterior uterine wall,surrounded by peritrophoblastic vasculature.(2) Treatment outcome: diagnosis of gestational trophoblastic neoplasm was suspected or made in 20 patients,four of whom were even treated by chemotherapy.MTX therapy was given to 3 patients,2 of whom were cured.Dilation and curettages were given to 16 patients,11 of whom were cured.8 patients underwent curettage with sonographic guidance after uterine artery embolism,and 8 patients with laparoscopic or hysteroscopic guidance.All of 15 patients underwent excision of CSP lesion via laparoscopy were cured.4 patients were treated by TAH.(3) Time of in hospital and operation:in laparoscopy group,the average hospitalization days were (3.5 ± 1.6) days,the average operation duration was (54 ± 16)minutes.In laparotomy group,the average hospitalization days were (9.7 ± 5.8) days,and the average surgical duration was (87 ± 15) minutes.It reached significant difference (P ＜ 0.05).Conclusions CSP with sonographic mass was the consequence of continued growth of residual pregnancy mass after incomplete abortion or curettage of CSP with gestation sac.The similar sonographic image might lead to misdiagnosis.Individual therapy was recommended.Excision of CSP lesion via laparoscopy might be the primary option for its advantages in differential diagnosis,caesarean scar defect repair and successful ratio.

Objective To approach the efficiency and feasibility of preserving the fertility for patients with placental site trophoblastic tumor ( PSTT ).Methods Totally 2 086 cases of gestational trophoblastic neoplasm ( GTN) patients registered in Peking Union Medical College Hospital between 1998 and 2013.Fifty-seven of them were PSTT patients , 40 cases of which suffered hysterectomy , the rest 17 PSTT patients who preserved their fertility were analyzed retrospectively.The computerized database of clinical and pathological reports was reviewed in this cohort.Results The clinical manifestation of PSTT was not specific compared to other types of GTN.The average age of the 17 patients was 29.5 years old (range 22-39 years).The most common antecedent pregnancy was term birth (8 cases), the others were spontaneous abortion in 4 case, artificial abortion in 3 cases and molar pregnancy in 2 cases.The baseline serum β-hCG was slightly elevated and 12 patients (12/15) were less than 1 000 U/L.In this cohort, nine of the patients were in stage Ⅰ, while the other eight cases were in stage Ⅲ .The patients suffered conservative surgery, including dilation and curettage of uterus in 7 cases, open abdomen uterine lesion excision in 4 cases, laparoscopic uterine lesion excision in 3 cases, hysteroscopic uterine lesion excision in 1 case, and pulmonary lobectomy in 2 cases.Two of the patients didn′t received chemotherapy , while the other 15 cases suffered combination chemotherapy.Compared with 40 patients who suffered hysterectomy during the same interval , fertility preservation group did not result in poor outcomes or high risk of relapse rate.Six subsequent pregnancies happened after the therapy , two of them were during their second-trimester, while four patients had healthy babies by vaginal delivery in two and cesarean section in two .The scar of the uterus was fairly well during the cesarean sections.Conclusions Reservation of fertility therapy could be considered in highly-selected patients for young women who strongly desired to preserve their fertility and with localized lesion.Exactitude follow-up after therapy should be recommended.Contraception should also be recommended for at least one year after the chemotherapy.Vaginal delivery could be an option for the future pregnancies.

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 Ⅰ b2 - Ⅱb cervical cancer treated with neoadjuvant chemotherapy followed by radical hysterectomy.Methods From January 1999 to December 2010,111 patients with FIGO stage Ⅰ b2 - Ⅱ b 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 ×109/L,respectively.Chemotherapy response was evaluated according to the WHO criteria,including complete response (CR),partial response (PR),arable disease (SD) and progressive disease (PD).Patients who achieved CR or PR were defined as responder.Rates of clinical response were compared with the clinicalpathological 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.

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.