Junjun Yang

Diagnosis and management of uterine arteriovenous fistulas with massive vaginal bleeding

To study the clinical manifestations, diagnosis, management, and prognosis of uterine arteriovenous fistulas with massive vaginal bleeding.

The switch from ER stress-induced apoptosis to autophagy via ROS-mediated JNK/p62 signals: A survival mechanism in methotrexate-resistant choriocarcinoma cells.

BACKGROUND Human choriocarcinoma, a highly curable solid tumour, is exceptionally sensitive to methotrexate-based chemotherapy at the metastatic stage. The present study aimed to investigate the molecular basis for this resistance to methotrexate therapy occurs in some cases, and these patients subsequently die from progressive and advanced disease. METHODS The autophagy and apoptotic activity regulated by PERK/ATF4 axis in methotrexate-resistant JEG-3 and parental cells were evaluated with western blotting and chromatin immunoprecipitation (ChIP). The regulatory relationships among the reactive oxygen species (ROS), JNK/p62 axis, PERK/ATF4-mediated apoptosis and autophagy were assessed with western blotting, RT-PCR, fluorescence-activated cell sorting as well as ChIP. RESULTS The decreased apoptosis in methotrexate-resistant JEG-3 cells was observed with an up-regulation of protective autophagy, suggesting a switch from apoptosis to autophagy, which was regulated via the PERK/ATF4 pathway under condition of endoplasmic reticulum (ER) stress. Further experiments demonstrated that this cell death switch was regulated by ROS-mediated JNK/p62 pathway and subsequently lead to the resistance of choriocarcinoma cells to methotrexate treatment. CONCLUSIONS This study provides evidence to explain a survival mechanism of the switch from ER stress-induced apoptosis to autophagy via ROS-mediated JNK/p62 signals in methotrexate-resistant choriocarcinoma cells and may implicate the chemotherapy of methotrexate resistance in choriocarcinoma.

Emergency craniotomy in patients with intracranial metastatic gestational trophoblastic tumor

To study the diagnosis, management and prognosis of intracranial metastases of gestational trophoblastic tumor (GTT) patients who had emergency craniotomy.

Placental site trophoblastic tumor: A review of 108 cases and their implications for prognosis and treatment

OBJECTIVE To identify important prognostic factors and optimized treatment strategies through the analysis of the clinical and pathological characteristics of placental site trophoblastic tumor. METHODS 108 patients with PSTT registered in two GTD centers or in six tertiary hospitals in China were analyzed retrospectively between the years 1998 and 2013. The computerized database of clinical and pathological reports was reviewed on this patient group. The data were subsequently analyzed retrospectively using SPSS software. RESULTS Among 3581 patients with GTNs treated in GTD centers or in the tertiary hospitals between 1998 and 2013, 108 cases were histologically confirmed PSTT (3%). Only seven deaths and eleven relapse cases were observed. All seven of the deaths were disease related, due to chemotherapy-resistant or relapsed. 23 patients who received fertility preservation treatment did not experience poor outcome or high risk of relapse. In 71 patients with International Federation of Gynecology and Obstetrics (FIGO) stage I disease, the use of adjuvant chemotherapy following surgery (n=49) or not (n=22) made no significant difference in relapse rate (P=0.303) or survival (P=0.782). Univariate analysis revealed the interval between antecedent pregnancy and onset of PSTT, stage, prognosis score, and necrosis as significant predictors of poor survival but only stage remained significant on multivariate analysis. CONCLUSIONS Patients with FIGO stage IV disease demonstrate the most critical risk indicator of PSTT in the current study. Preservation of fertility is considered in highly-selected patients with localized tumor; and surgery without chemotherapy is recommended as first line treatment for patients with stage I who are at low-risk.

Analysis of the prognosis and related factors for patients with stage IV gestational trophoblastic neoplasia.

Objective This study aimed to investigate and analyze the treatments and prognoses of patients with stage IV gestational trophoblastic neoplasia (GTN). Methods Between January 1990 and January 2010, 105 patients with stage IV GTN were treated in our hospital (Peking Union Medical College Hospital). A retrospective study is presented herein to report the prognoses of these patients and to statistically analyze the risk factors that affected the prognoses of patients with stage IV GTN. Results After the treatments, of the 105 patients, 71 (67.6%) patients achieved complete remission, 15 (14.3%) patients exhibited partial remission, and 19 (18.1%) patients exhibited progression of the disease. In total, of the 105 patients, 30 (28.6%) patients died. Our statistical analyses have revealed that a previously failed multidrug chemotherapy history, multiorgan metastasis concomitant with renal metastasis, and surgical intervention all affected the prognoses of patients with stage IV GTN. In addition, patients with stage IV GTN with International Federation of Gynecology and Obstetrics scores below 12 were relatively more likely to obtain complete remission. Conclusions Multidrug, multiroute chemotherapy, assisted by surgery when necessary, is the predominant strategy for patients with stage IV GTN. Fluorouracil-based multidrug chemotherapy can produce good outcomes for patients with stage IV GTN who were treated primarily. Adequate attention should be given to patients who have previously failed multidrug chemotherapy, have experienced multiorgan metastasis concomitant with renal metastasis, or have International Federation of Gynecology and Obstetrics scores of more than 12.

The landscape of alternative splicing in cervical squamous cell carcinoma.

Background Alternative splicing (AS) is a key regulatory mechanism in protein synthesis and proteome diversity. In this study, we identified alternative splicing events in four pairs of cervical squamous cell carcinoma (CSCC) and adjacent nontumor tissues using RNA sequencing. Methods The transcripts of the four paired samples were thoroughly analyzed by RNA sequencing. SpliceMap software was used to detect the splicing junctions. Kyoto Encyclopedia of Genes and Genomes pathway analysis was conducted to detect the alternative spliced genes-related signal pathways. The alternative spliced genes were validated by reverse transcription-polymerase chain reaction (RT-PCR). Results There were 35 common alternative spliced genes in the four CSCC samples; they were novel and CSCC specific. Sixteen pathways were significantly enriched (P<0.05). One novel 5′AS site in the KLHDC7B gene, encoding kelch domain-containing 7B, and an exon-skipping site in the SYCP2 gene, encoding synaptonemal complex 2, were validated by RT-PCR. The KLHDC7B gene with 5′AS was found in 67.5% (27/40) of CSCC samples and was significantly related with cellular differentiation and tumor size. The exon-skipping site of the SYCP2 gene was found in 35.0% (14/40) of CSCC samples and was significantly related with depth of cervical invasion. Conclusion The KLHDC7B and the SYCP2 genes with alternative spliced events might be involved in the development and progression of CSCC and could be used as biomarkers in the diagnosis and prognosis of CSCC.

Fertility-sparing uterine lesion resection for young women with gestational trophoblastic neoplasias: single institution experience.

Purpose To evaluate the oncological safety and pregnant outcomes of fertility-sparing uterine lesion resection in treating gestational trophoblastic neoplasias. Results After the treatment of surgery and chemotherapy, all the patients achieved complete remission. With a median follow-up time of 44 months (range, 6-188), 3 patients (3.85%) relapsed within 3-26 months. Multivariate analysis showed that tumor size was the independent risk factor of recurrence and the cutoff value was 4.2cm. Among 37 patients who attempted to conceive, 31 achieved clinical pregnancy. The rate of pregnancy and live birth were 83.8% and 77.4%. Uterine rupture did not occurred no matter in cesarean section or vaginal delivery. No congenital abnormalities were reported among the live births. Methods From January 1995 to December 2014, 78 patients with gestational trophoblastic neoplasias who underwent fertility-sparing uterine lesion resection at Peking Union Medical College Hospital were reviewed. The complete remission rate, fertility rate, pregnant outcomes and risk factors of recurrence were analyzed. Conclusions Fertility-sparing uterine lesion resection might be considered as a safe and reasonable alternative for high-selected young women to remove uterine lesion in the treatment of gestational trophoblastic neoplasias.

Primary treatment of stage IV gestational trophoblastic neoplasia with floxuridine, dactinomycin, etoposide and vincristine (FAEV): A report based on our 10-year clinical experiences

OBJECTIVE To evaluate the efficacy and toxicity profile of floxuridine, dactinomycin, etoposide and vincristine (FAEV) regimen as primary treatment in stage IV gestational trophoblastic neoplasia (GTN). METHODS From 2004 to 2014, FAEV was given to 30 stage IV GTNs as the primary treatment (at least two cycles) in Peking Union Medical College Hospital. Remission/resistance/recurrence rate, the cause of treatment failure, and the toxicity profile were analyzed. RESULTS A total of 190cycles of FAEV were administered to 30 patients; the median number of the cycles was 6 (range 3-11). The median follow up was 52.3months (range 8-120). Of all the patients received FAEV primarily, 24 achieved complete remission after only received FAEV, with no recurrence; 6 patients later switched to EMA-CO treatment due to FAEV resistance. Among the 6 patients, 2 died of progressive disease after multiple lines of chemotherapy, the other 4 achieved complete remission after second-line or third-line chemotherapy and 1 of them relapsed 15months later. FAEV was well tolerated. No one died from toxicity. Severe grade 4 neutropenia and thrombocytopenia were noted in 8 (26.7%) and 2 (6.7%) cases. No secondary malignancy was observed with follow-ups from 8 to120 months. Patients treated with FAEV showed good reproductive outcomes. CONCLUSIONS FAEV regimen might be considered as an alternative to other chemotherapy regimen in the primary treatment of stage IV GTN, where it had a high rate of remission and a tolerable toxicity.

Identification and treatment of gestational trophoblastic neoplasia located in the cesarean scar

To identify the clinical characteristics of, and the diagnostic and therapeutic strategies for, gestational trophoblastic neoplasia (GTN) located in the cesarean scar.

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 (β-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.