Advanced ovarian yolk sac tumor: upfront surgery or neoadjuvant chemotherapy followed by interval debulking?

OBJECTIVE: To compare surgery and survival outcomes between neoadjuvant chemotherapy and primary debulking surgery in patients with advanced ovarian yolk sac tumor. METHODS: In this retrospective cohort analysis, patients with stage III to IV ovarian yolk sac tumor or mixed germ cell tumors containing yolk sac tumor elements, and who underwent surgery at Peking Union Medical College Hospital between January 2011 and December 2021, were identified. Patient characteristics, treatment, and survival data were analyzed between the two groups. RESULTS: A total of 40 patients were enrolled: 19 patients received neoadjuvant chemotherapy followed by interval surgery, and 21 patients were treated with primary debulking surgery. After neoadjuvant chemotherapy, the surgical conditions of patients were improved. All patients achieved cytoreduction to R0 or R1 at interval surgery. No statistical difference was found in 3-year disease-free survival and overall survival between the neoadjuvant chemotherapy group and the primary debulking surgery group (log rank p=0.4 and 0.94). Patients had less blood loss (328.4 vs 1285.7 mL, p=0.029), lower transfusion volume (1044.4 vs 3066.7 mL, p=0.011), and fewer peri-operative complications (15.8% vs 47.6%, p=0.032) at the interval debulking surgery after neoadjuvant chemotherapy compared with patients who underwent primary debulking surgery. CONCLUSION: For patients with advanced-stage ovarian yolk sac tumor, neoadjuvant chemotherapy followed by interval surgery is an alternative option, especially for those who cannot tolerate the primary debulking surgery because of high tumor burden and vulnerable status.

CDC50A might be a novel biomarker of epithelial ovarian cancer-initiating cells.

BACKGROUND: The aim of this work was to screen and validate biomarkers of ovarian cancer-initiating cells to detect the mechanisms of recurrence of epithelial ovarian cancer (EOC). METHODS: Stably labelled the amino acid in side population (SP) cells of epithelial ovarian cancer which were rich in cancer-initiating cells and non-SP cells with isotope in culture and differentially expressed cellular membrane proteins in SP cells were identified through proteomics technology. The new candidate biomarker was screened and validated through RT-PCR and western blot. Both in cell lines and primary EOC, cancer-initiating biofunctions of CDC50A positive cells were validated. Moreover, the characteristics of mesenchymal transition (EMT) was also detected and the correlation between the biomarker and clinical prognosis was observed. RESULTS: Through proteomics technology, candidate protein CDC50A was screened, and its significantly differential expression in SP cells was validated. CDC50A-positive cells from cell lines and primary ovarian cancer tissues were validated to show characteristics of cancer-initiating cells both in vitro and in vivo, including sphere-forming, self-renewal, differentiation, tumor metastasis and tumorigenicity in mice. The relationship between CDC50A-positive cells from primary tissues and tumour metastasis was confirmed based on their mesenchymal transition characteristics. Among 16 high-grade ovarian serous cancer patients, a high ratio of CDC50A-positive cells in primary tumours was correlated with a shorter platinum-free interval (p = 0.031, HR 0.260, 95% CI 0.77 ~ 0.885). CONCLUSION: CDC50A could be used to screen ovarian cancer-initiating cells and might be a new target to resolve tumour development in EOC patients.

Low-grade endometrial stromal sarcoma with intracaval or intracardiac extension: a retrospective study of eight cases.

PURPOSE: This study aimed to improve the knowledge of low-grade endometrial stromal sarcoma (LG-ESS) with intracaval or intracardiac extension and tried to identify the potential risk factors and optimal treatment method influencing prognosis. METHODS: We performed a retrospective review of eight LG-ESS patients with intracaval or intracardiac extension who underwent treatment at Peking Union Medical College Hospital between 2012 and 2020. RESULTS: The median age at diagnosis was 44 years, ranging from 28 to 56 years. Abnormal uterine bleeding was the most common intimal symptom (3/8), followed by low back discomfort (2/8), edema of the lower limbs (2/8), abdominal pain (1/8), and dyspnea (1/8). All patients underwent resection of the intravascular and extravascular portions of the tumor. Two patients were in stage IIIC, and six were in stage IVB. After surgery, four patients received adjuvant radiotherapy, of whom three also received letrozole. One patient was treated with letrozole alone, and one patient received medroxyprogesterone. The average follow-up time was 34.5 months, ranging from 6 to 98 months. No patients died or relapsed during the follow-up period. CONCLUSIONS: LG-ESS with intracaval or intracardiac extension is an uncommon type of tumor which is easily misdiagnosed and can only be diagnosed by histological evaluation after surgery. Complete tumoral excision followed by adjuvant therapy may benefit patient survival time. Long-term follow-up is essential due to the high rate of late recurrence.

Diagnosis and management of growing teratoma syndrome after ovarian immature teratoma: A single center experience.

OBJECTIVES: To evaluate the diagnostic, surgical, and oncological outcomes of patients with growing teratoma syndrome (GTS). METHODS: Patients diagnosed with ovarian immature teratoma (IMT) between 1980 and 2018 at Peking Union Medical College Hospital (PUMCH) were evaluated for the development of GTS. Their clinical characteristics, surgical and pathological data, and oncological outcomes were collected. RESULTS: Between 1980 and 2018, 175 cases of IMT were referred to PUMCH. Thirty-five patients subsequently developed GTS with a crude rate of approximately 20%. The median interval between the initial diagnosis of IMT and the first occurrence of GTS was 18.5 months (range, 6-78 months). Residual disease (P < 0.001) and gliomatosis peritonei (GP) at initial surgery (P = 0.023) were independent risk factors for GTS development. Fertility-sparing surgery for GTS was performed in 27 patients and four patients achieved five singleton pregnancies. The median follow-up time was 73 months (range, 11-401 months). Eleven patients developed at least one recurrence. Residual disease after GTS surgery was associated with GTS recurrence (P = 0.001). By the end of follow-up, 27 patients were alive without disease and the other eight patients were alive with disease. CONCLUSION: The presence of residual disease and GP at initial surgery are risk factors for GTS. Complete surgical resection is the cornerstone for treatment of GTS. The presence of residual disease after surgery for GTS is a risk factor for GTS recurrence. Fertility-sparing surgery should be performed because spontaneous pregnancy is possible. The overall prognosis of GTS is excellent.

Outcomes and prognostic factors of patients with recurrent and persistent malignant ovarian germ cell tumors.

OBJECTIVE: Due to the rarity of recurrent and persistent malignant ovarian germ cell tumors (MOGCTs), there is no standardized protocol for salvage therapy. This study aimed to investigate the outcomes and prognostic factors of patients with recurrent and persistent MOGCTs. METHODS: Clinical data for 59 patients with recurrent and persistent MOGCTs admitted to Peking Union Medical College Hospital from January 1, 2000, to April 30, 2018, were retrospectively analyzed. RESULTS: Twenty-one cases (35.6%) were recurrent, and 38 (64.4%) were persistent. Patient age ranged from 1 to 39 years, and disease stage was as follows: 33 stage I, 4 stage II, 21 stage III, and 1 stage IV. There were 19 immature teratomas, 26 yolk sac tumors, 1 dysgerminoma, and 13 mixed germ cell tumors. Regarding the primary surgery, fertility was preserved in 49 patients and not preserved in 10 patients. Among the patients who underwent fertility-preserving primary surgery, 40 had fertility preserved in the second operation, and 9 did not. In the mean follow-up of 52.6 months (range 2-279 months) after recurrence, 19 patients (32.2%) experienced a second relapse, and 16 (27.1%) died. The 5-year survival and progression-free survival rates after relapse were 70.0% and 67.0%, respectively. The optimal salvage surgery and chemotherapy regimen after relapse were independent prognostic factors (P < 0.05). CONCLUSIONS: The prognosis of recurrent and persistent MOGCTs was good after salvage therapy. The optimal salvage surgery and adjuvant standardized chemotherapy significantly impact patient prognosis. For young nulliparous patients, secondary fertility-sparing salvage therapy can be considered.

Analysis of oncologic and reproductive outcomes after fertility-sparing surgery in apparent stage I adult ovarian granulosa cell tumors.

OBJECTIVE: We evaluated the oncological and reproductive outcomes after fertility-sparing surgery (FSS) in patients with a stage I adult ovarian granulosa cell tumor (AGCT). METHODS: The medical records of patients aged <50 years with a stage I AGCT who underwent surgery between January 1983 and April 2017 were reviewed. Fertility-sparing surgery was defined as the preservation of the uterus and at least one adnexa. Outcomes were compared between groups who underwent FSS or radical surgery. Patients who had undergone FSS were contacted to gather reproductive outcomes and menstrual histories. RESULTS: A total of 113 patients who met the inclusion criteria were included: 61 had FSS while 52 underwent radical surgery. After a median follow-up of 99.2 months (range 20.2-394.3 months), 30 patients had recurrent disease (17 in the FSS group and 13 in the radical surgery group). Multivariate analysis showed no difference in disease-free survival between the groups who underwent FSS or radical surgery (P = 0.550). In patients who underwent FSS, incomplete staging was significantly associated with the risk of recurrence (P = 0.024). Of the 22 patients desiring pregnancy, 19 achieved 20 singleton pregnancies. The pregnancy rate was 86.4% and the live birth rate was 95%. CONCLUSIONS: FSS is an acceptable option for young patients who wish to preserve their fertility. Secondary surgical staging is an important treatment in patients with an unstaged AGCT. Reproductive outcomes are promising. Radical surgery might be delayed until recurrence, provided they are willing to undergo a prolonged follow-up.

Oncofertility in patients with stage I epithelial ovarian cancer: fertility-sparing surgery in young women of reproductive age.

BACKGROUND: Fertility-sparing surgery is indicated for patients with stage I epithelial ovarian cancers. We sought to evaluate the clinical outcomes and oncofertility in a cohort of patients of reproductive age with stage I epithelial ovarian cancer (EOC). METHODS: Overall, 108 patients of reproductive age (≤ 40 years) diagnosed with stage I EOC who were treated at Peking Union Medical College Hospital between 1999 and 2013 were included in the study. The Kaplan-Meier model and Cox regression analyses were used for the survival analysis. RESULTS: The type of surgery included fertility-sparing surgery (FSS) (48.1%) and radical surgery (RS) (51.9%). After a median follow-up of 83 months, we observed that grade 3 or clear-cell carcinoma was the only independent risk factor for disease-free survival and tumor-specific survival in the multivariate analysis. Patients with grade 3 or clear-cell carcinoma tended to be older than 30 years, have endometriosis, and undergo RS (p < 0.05). Fertility-sparing surgery did not affect disease-free survival or tumor-specific survival among patients of reproductive age with stage I EOC and among high-risk patients with stage IC2-3, grade 3, or clear-cell carcinoma. Thirty-four out of 52 (65.4%) FSS patients attempted to get pregnant. Twenty-eight (82.4%) achieved a successful pregnancy with a full-term delivery. CONCLUSIONS: Grade 3 or clear-cell carcinoma was the only independent risk factor for survival of patients of reproductive age with stage I EOC. FSS can be safely performed on patients of reproductive age with grade 1-2, stage I EOC. The safety of FSS for grade 3 and clear-cell carcinoma warrants further investigation.

Quantitative proteomic analysis of mitochondria from human ovarian cancer cells and their paclitaxel-resistant sublines.

Paclitaxel resistance is a major obstacle for the treatment of ovarian cancer. The chemoresistance mechanisms are partly related to the mitochondria. Identification of the relevant proteins in mitochondria will help in clarifying the possible mechanisms and in selecting effective chemotherapy for patients with paclitaxel resistance. In the present study, mitochondria from two paclitaxel-sensitive human ovarian cancer cell lines (SKOV3 and A2780) and their corresponding resistant cell lines (SKOV3-TR and A2780-TR) were isolated. Guanidine-modified acetyl-stable isotope labeling and liquid chromatography-hybrid linear ion trap Fourier-transform ion cyclotron resonance mass spectrometry (LC-FTICR MS) were performed to find the expressed differential proteins. Comparative proteomic analysis revealed eight differentially expressed proteins in the ovarian cancer cells and their paclitaxel-resistant sublines. Among them, mimitin and 14-3-3 ζ/δ were selected for further research. The effects of mimitin and 14-3-3 ζ/δ were explored using specific siRNA interference in ovarian cancer cell lines and immunohistochemistry in human tissue specimens. The downregulation of mimitin and 14-3-3 ζ/δ using specific siRNA in paclitaxel-resistant ovarian cancer cells led to an increase in the resistance index to paclitaxel. Multivariate analyses demonstrated that lower expression levels of the mimitin and 14-3-3 ζ/δ proteins were positively associated with shorter progression-free survival (PFS) and overall survival (OS) in patients with primary ovarian cancer (mimitin: PFS: P = 0.041, OS: P = 0.003; 14-3-3 ζ/δ: PFS: P = 0.031, OS: P = 0.011). Mimitin and 14-3-3 protein ζ/δ are potential markers of paclitaxel resistance and prognostic factors in ovarian cancer.

[Current status and outcomes of pelvic exenteration for recurrent cervical cancer: a systematic review].

OBJECTIVE: To evaluate the current status and outcomes of pelvic exenteration (PE) for recurrent cervical cancer. METHODS: The following electronic databases has been searched on recurrent cervical cancer management and treatment:Chinese Biological Medicine Disk (CBM), PubMed and Cochrane library. All retrieved studies had to fulfill the following inclusion criteria: cohort studies of recurrent cervical cancer, containing information of detailed patient and operation characteristics as well as the survival rate. Only publications in the English literature were included. All eligible literatures between Jan. 1990 and Aug. 2013 were assessed for quality. Relevant basic characteristics, complications, survival rate and prognostic factors were reviewed. RESULTS: There were eight trials involving 607 patients with cervical cancer received PE, including 515 cases with recurrent disease and 92 cases with primary disease. Four hundred and ninety patients had received total pelvic exenteration (TPE) operation, 103 underwent anterior pelvic exenteration (APE) and 14 received posterior pelvic exenteration (PPE). The 5-year overall survival rate for recurrent cervical cancer fluctuate from 26.7% to 56.0%. Complication rates were from 34.3% to 83.3% and the mortality rate was 1.2% (7/607). Among the relevant factors affecting survival time, resection margin status seemed to be the most important. CONCLUSION: Based on this systematic review, PE does help improve the survival of recurrent cervical cancer patients on the basis of strict selection of candidates.

[Clinical study on 68 cases with struma ovarii].

OBJECTIVE: To study the clinical features, treatment and prognosis of struma ovarii. METHODS: From January 1990 to January 2012, a total of 68 patients were diagnosed struma ovarii at the Department of Obstetrics and Gynecology, Peking Union Medical College Hospital. Clinical data of these patients were studied retrospectively. RESULTS: (1) Characteristics of patients: the median age of patients was 42 years old (17-81 years). Of those patients, 64 cases (94%) were diagnosed begin struma ovarii and 4 (6%) were malignant struma ovarii. (2) CLINICAL FEATURE: 32(47%, 32/68) patients were identified with pelvic mass by ultrasonic test, 28 cases(41%) had clinical abdominal pain, 8 (12%) touched a mass from abdominal wall. Preoperative CA(125) were tested in 54 patients, but only 8 cases (15%) had moderate elevation. All patients receive ultrasound examination, and 51 cases (75%) were mulitcystic lesions with many septi, 3 (4%) solid lesions and 14 (21%) solid-cystic tumors. The mean diameter of tumors was (8 ± 3) cm. Ascites was present in 4 (6%, 4/68) patients. Sixty-seven patients had unilateral lesions, and 1 patient had bilateral lesions. No patient had hyperthyroidism presentation. Nineteen cases underwent thyroid function test after operation, and the results were normal. (3) TREATMENT: all patients underwent surgical treatment. Among patients with begin struma ovarii, 25 cases underwent cystectomy, 15 cases unilateral, 2 bilateral salpingo-oophorectomy, 22 cases hysterectomy + unilateral or bilateral salpingo-oophorectomy. Four malignant struma ovarii, 1 patient underwent fertility-sparing staging surgery, 2 patients unilateral salpingo-oophorectomy, 1 case hysterectomy + bilateral salpingo-oophorectomy. Two patients received chemotherapy after surgery. (4) PROGNOSIS: all patients were followed up in Peking Union Medical College Hospital. The median follow-up time of benign struma ovarii was 5.4 years (6 months-21 years) and there were no recurrence. The median follow-up time of malignant struma ovarii was 11.5 years (9-20 years). Three cases had long-term recurrence at 2, 7 and 16 years respectively after surgery. They were received surgical treatment after recurrence and all were alive. Two cases were given by thyroidectomy and ¹³¹I treatment. CONCLUSIONS: Struma ovarii is a rare ovarian monodermal teratoma. Tumorectomy or salpingo-oophorectomy is the appropriate therapeutic treatment for benign struma ovarii. The incidence of malignant struma ovarii is low, and there are no standard treatments. Because of higher long-term recurrence rate, these patients need close follow-up.

[Oncologic and fertility outcomes of young patients with early stage of cervical cancer treated by vaginal radical trachelectomy].

OBJECTIVE: To evaluate the prognosis and fertility outcomes of patients with early stage of cervical cancer treated by vaginal radical trachelectomy (VRT) in combination with laparoscopic pelvic lymphadenectomy. METHODS: The surgical data, disease recurrences and fertility outcomes were analyzed retrospectively for 51 patients who received VRT in Peking Union Medical College Hospital from Dec. 2003 to Nov. 2013. RESULTS: Forty-eight patients succeeded in preserving fertility. The median age was 29 years. International Federation of Gynecology and Obstetrics (FIGO) stage: 5 cases Ia1 with lymph vascular space invasion (LVSI), 4 cases Ia2 and 39 cases in stage Ib1. Tumor size: 20 cases with no visible lesion, 20 cases with tumor size ≤ 2 cm, 8 cases with tumor size > 2 cm. Histological type: 42 cases with squamous carcinoma, 6 cases with adenocarcinoma or adeno-squamous carcinoma. The mean excised cervical length and parametrial width was (2.6 ± 0.6) cm and (1.9 ± 0.5) cm, respectively. Six recurrences (12%) were observed after following up for a mean duration of (35 ± 21) months. The recurrent rate in patients with tumor size > 2 cm was 3/8, which was significantly higher than that of the patients with tumor size ≤ 2 cm (8%, 3/40;P < 0.01). Of the 35 patients who desired to conceive after the surgery, 13 women had 17 pregnancies and the pregnant rate was 37% (13/35). Nine women obtained 10 healthy live birth babies. The fertility rate was 26% (9/35). CONCLUSIONS: VRT in combination with laparoscopic pelvic lymphadenectomy could preserve the fertility of patients with early stage of cervical cancer with acceptable oncologic and fertility outcomes. Tumor size ≤ 2 cm should be emphasized as the indication of VRT in considering of the higher recurrent rate in patients with tumor size > 2 cm.

Fertility-sparing surgery in children and adolescents with borderline ovarian tumors: a retrospective study.

OBJECTIVE: To describe the characteristics of children and adolescents with borderline ovarian tumors (BOTs) and evaluate the efficacy and safety of fertility-sparing surgery (FSS) in these patients. METHODS: Patients with BOTs younger than 20 years who underwent FSS were included in this study. RESULTS: A total of 34 patients were included, with a median patient age of 17 (range, 3-19) years; 97.1% (33/34) of cases occurred after menarche. Of the patients, 82.4% had mucinous borderline tumors (MBOTs), 14.7% had serous borderline tumors (SBOTs), and 2.9% had seromucinous borderline tumor (SMBOT). The median tumor size was 20.4 (range, 8-40)cm. All patients were at International Federation of Gynecology and Obstetrics stage I and all underwent FSS: cystectomy (unilateral ovarian cystectomy, UC, 14/34, 41.2% and bilateral ovarian cystectomy, BC, 1/34, 2.9%), unilateral salpingo-oophorectomy (USO; 18/34; 52.9%), or USO + contralateral ovarian cystectomy (1/34; 2.9%). The median follow-up time was 65 (range, 10-148) months. Recurrence was experienced by 10 of the 34 patients (29.4%). One patient with SBOT experienced progression to low-grade serous carcinoma after the third relapse. Two patients had a total of four pregnancies, resulting in three live births. The recurrence rate of UC was significantly higher in MBOTs than in USO (p = 0.005). The 5-year disease-free survival rate was 67.1%, and the 5-year overall survival rate was 100%. CONCLUSIONS: Fertility-sparing surgery is feasible and safe for children and adolescents with BOTs. For patients with MBOTs, USO is recommended to lower the risk of recurrence.

Cell-cycle synchronization reverses Taxol resistance of human ovarian cancer cell lines.

BACKGROUND: Taxol is a powerful chemotherapy agent leading to mitotic arrest and cell death; however, its clinical efficacy has been hampered due to the development of drug resistance. Taxol specifically targets the cell cycle. Progress through mitosis (M stage) is an absolute requirement for drug-induced death because cell death is markedly reduced in cells blocked at the G1-S transition. The measured doubling time for ovarian cancer cells is about 27 h. As such, during treatment with Taxol most of the cells are not in the M stage of the cell cycle. Thus, the effect of cell-cycle synchronization was investigated in regard to reversing Taxol resistance in ovarian cancer cells. METHODS: Giemsa-Wright staining was used for assessing the morphology of the cells. The doubling time of the cells was calculated using formula as follows: Td = In2/slope. The resistant index and cell cycle were measured via MTT assays and flow cytometry. Thymidine was used to induce cell-cycle synchronization, and cell apoptosis rates following exposure to Taxol were measured using a flow cytometer. RESULTS: The growth doubling time of two Taxol-resistant cell lines were longer than that of Taxol-sensitive cells. Apoptotic rates in Taxol-sensitive and -resistant cell lines after synchronization and exposure to Taxol were all higher compared to unsynchronized controls (p <0.05). CONCLUSIONS: Synchronization of the cell-cycle resulted in an increased effectiveness of Taxol toward ovarian cancer cell lines. We speculated that formation of drug resistance toward Taxol in ovarian cancer could be partly attributed to the longer doubling time of these cells.

Clinical outcomes of levonorgestrel-releasing intrauterine device present during controlled ovarian stimulation in patients with early stage endometrioid adenocarcinoma and atypical endometrial hyperplasia after fertility-sparing treatments: 10-year experience in one tertiary hospital in China.

BACKGROUND: To evaluate the oncologic and pregnancy outcomes of patients with early stage endometrioid adenocarcinoma (EMC) and atypical endometrial hyperplasia (AEH) treated with controlled ovarian stimulation (COS) with or without levonorgestrel-releasing intrauterine device (LNG-IUD) after fertility-sparing treatment (FSTs). METHODS: A total of 67 patients with EMC or AEH who achieved complete response after FSTs and underwent COS between January 2010 and December 2019 were retrospectively reviewed. Univariate and multivariate Cox regression analyses were used to evaluate the risk factors for recurrence after COS. RESULTS: The average age was 32.9 ± 3.46 years. 23.9 % of these patients relapsed after COS during the follow-up period. The 2-year cumulative recurrence rate was 14.9 % (9.1 % and 20.6 % in the LNG-IUD and control groups, respectively). Compared with the control group, the recurrence rate was lower in patients with LNG-IUDs present during COS (12.1 % vs 35.5 %, p = 0.027). The clinical pregnancy (42.4 % vs 52.9 %, p = 0.392) and live birth (21.2 % vs 29.4 %, p = 0.444) rates were similar between the LNG-IUD and control groups. Age, body mass index (BMI), histology, FST type and time to complete response were not related to prognosis after COS. After adjusting for age and BMI in a multivariate Cox regression model, the use of LNG-IUD during COS was a favorable factor for better oncologic outcomes after COS (HR 0.263, 95 %CI 0.084-0.822, p = 0.022). CONCLUSIONS: Patients with early stage EMC and AEH treated with assisted reproductive technology after FSTs might benefit from LNG-IUDs present during COS.

Oncological and Reproductive Outcomes after Fertility-Sparing Surgery in Patients with Advanced-Stage Serous Borderline Ovarian Tumor: A Single-Center Retrospective Study.

Our study aimed to analyze the prognosis and reproductive outcomes of patients with advanced-stage serous borderline ovarian tumors (SBOTs) who underwent fertility-sparing surgery (FSS). This study included patients aged ≤ 45 years diagnosed with advanced-stage (International Federation of Gynecology and Obstetrics II and III) SBOTs who were treated with FSS. Conservative surgeries were performed in 65 patients with advanced-stage SBOT with a median age of 28 years (range, 16-44 years). Nine patients had invasive implants. The median follow-up was 81.7 months. Forty-six patients (70.8%) had a relapse (median time to first recurrence, 22.8 months). Thirteen patients subsequently developed recurrence as an invasive disease, and two died due to disease progression. After multivariate analysis, age < 30 years and incomplete cytoreduction were independent risk factors for recurrence. Invasive implants and postoperative residual tumors were significantly associated with shorter disease-free survival. Of 35 patients attempting to conceive, 12 underwent assisted reproductive technology. Additionally, 19 pregnancies, including 15 full-term births, were documented. FSS provides a good chance of reproductive success in women with advanced-stage SBOT who desire fertility preservation, but it has a high recurrence rate and risk of malignancy transformation. Patients with invasive implants should be strictly selected for FSS.

Whole exome sequencing identifies common mutational landscape of cervix and endometrium small cell neuroendocrine carcinoma.

Background: Primary small cell neuroendocrine carcinomas of the cervix and endometrium are rare gynecological malignancies with limited treatment options. This study aimed to improve the understanding of the carcinogenesis process and identify potential therapeutic targets for these two tumor types by constructing the mutational landscape at the whole exome level. Methods: Primary tumor tissues and their matched blood samples were obtained from 10 patients with small cell cervical neuroendocrine carcinoma (NECC) and five patients with small cell endometrial neuroendocrine carcinoma (NECE). Whole exome sequencing was performed to construct the somatic mutation profiles. Mutational signature and recurrent mutated gene analysis were used to identify tumor subtypes and common carcinogenesis processes. Results: Based on the burden of different mutational signatures, the NECCs in this work can be divided into two subtypes, including the mismatch repair deficiency like (dMMR-like) type (4/10) and the high spontaneous deamination type (6/10). Components of the PI3K/AKT signaling and RAS signaling were exclusively mutated in these two subtypes, respectively. The integration of human papillomavirus made a limited contribution to tumorigenesis in NECC (20%). The dysfunction of the mismatch repair system and microsatellite instability are the major features of NECE. PI3K/AKT, JAK/STAT signaling, and chromatin remodeling activity were the common mutated pathways in NECE. PIK3CA, WNK2, and KMT2B underwent mutations in both the dMMR-like subtype of NECC (50% - 75%) and in NECE (60% - 80%) specimens, while exhibiting infrequent mutational occurrences in publicly available data pertaining to neuroendocrine carcinomas of the lung or bladder (< 10%). Conclusion: We identified the two subtypes of NECC with distinct mutated pathways and potential therapy targets. The dMMR-like type NECC and NECE may share a similar carcinogenesis process that include dysfunction of PI3K/AKT signaling, cell cycle, antiapoptotic processes, and chromatin remodeling activity.

Treatment With Niraparib Maintenance Therapy in Patients With Newly Diagnosed Advanced Ovarian Cancer: A Phase 3 Randomized Clinical Trial.

Importance: The efficacy of niraparib maintenance therapy with an individualized starting dose (ISD) warrants further investigation in a broad population with newly diagnosed advanced ovarian cancer (aOC), including patients without postoperative residual disease. Objective: To evaluate the efficacy and safety of niraparib with an ISD in a broad population with newly diagnosed aOC (R0 resection permitted). Design, Setting, and Participants: This multicenter, randomized, double-blind, placebo-controlled, phase 3 study was conducted in China and enrolled 384 patients with newly diagnosed aOC who received primary or interval debulking surgery and responded to treatment with first-line platinum-based chemotherapy. By data cutoff (September 30, 2021), median follow-up for progression-free survival (PFS) was 27.5 (IQR, 24.7-30.4) months. Interventions: Patients were randomized 2:1 to receive niraparib or placebo with ISD (200 mg/d for those with a body weight of <77 kg and/or platelet count of <150 ×103/µL [to convert to ×109/µL, multiply by 1] at baseline; 300 mg/d otherwise) stratified by germline BRCA variant status, tumor homologous recombination deficiency status, neoadjuvant chemotherapy, and response to first-line platinum-based chemotherapy. Main Outcomes and Measurements: The primary end point was blinded, independent central review-assessed PFS in the intention-to-treat population. Results: A total of 384 patients were randomized (255 niraparib [66.4%]; median [range] age, 53 [32-77] years; 129 placebo [33.6%]; median [range] age, 54 [33-77] years), and 375 (247 niraparib [65.9%], 128 placebo [34.1%]) received treatment at a dose of 200 mg per day. Median PFS with niraparib vs placebo was 24.8 vs 8.3 months (hazard ratio [HR], 0.45; 95% CI, 0.34-0.60; P < .001) in the intention-to-treat population; not reached vs 10.8 months (HR, 0.40; 95% CI, 0.23-0.68) and 19.3 vs 8.3 months (HR, 0.48; 95% CI, 0.34-0.67) in patients with and without germline BRCA variants, respectively; not reached vs 11.0 months (HR, 0.48; 95% CI, 0.34-0.68) and 16.6 vs 5.5 months (HR, 0.41; 95% CI, 0.22-0.75) in homologous recombination deficient and proficient patients, respectively; and 24.8 vs 8.3 months (HR, 0.44; 95% CI, 0.32-0.61) and 16.5 vs 8.3 months (HR, 0.27; 95% CI, 0.10-0.72) in those with optimal and suboptimal debulking, respectively. Similar proportions of niraparib-treated and placebo-treated patients (6.7% vs 5.4%) discontinued treatment due to treatment-emergent adverse events. Conclusion and Relevance: This randomized clinical trial found that niraparib maintenance therapy prolonged PFS in patients with newly diagnosed aOC regardless of postoperative residual disease or biomarker status. The ISD was effective and safe in the first-line maintenance setting. Trial Registration: ClinicalTrials.gov Identifier: NCT03709316.

Secretion of annexin A3 from ovarian cancer cells and its association with platinum resistance in ovarian cancer patients.

Early detection of resistance to platinum-based therapy is critical for improving the treatment of ovarian cancers. We have previously found that increased expression of annexin A3 is a mechanism for platinum resistance in ovarian cancer cells. Here we demonstrate that annexin A3 can be detected in the culture medium of ovarian cancer cells, particularly these cells that express high levels of annexin A3. Levels of annexin A3 were then determined in sera from ovarian cancer patients using an enzyme-linked immunosorbent assay. Compared with those from normal donors, sera from ovarian cancer patients contain significantly higher levels of annexin A3. Furthermore, serum levels of annexin A3 were significantly higher in platinum-resistant patients than in platinum-sensitive patients. To gain insight into the mechanism of secretion, the ovarian cancer cell lines were examined using both transmission electron microscopy and immunoelectron microscopy. Compared with parent cells, there are significantly more vesicles in the cytoplasm of ovarian cancer cells that express high levels of annexin A3, and at least some vesicles are annexin A3-positive. Moreover, some vesicles appear to be fused with the cell membrane, suggesting that annexin A3 secretion may be associated with exocytosis and the release of exosomes. This is supported by our observation that ovarian cancer cells expressing higher levels of annexin A3 released increased numbers of exosomes. Furthermore, annexin A3 can be detected in exosomes released from cisplatin-resistant cells (SKOV3/Cis) by immunoblotting and immunoelectron microscopy.

[Management of invasive cervical cancer in pregnancy: clinical analysis of 13 cases].

OBJECTIVE: To analyze the clinical characteristics and assess the outcome of treatment for cervical cancer during pregnancy. METHODS: A cohort of 13 patients with cervical cancer diagnosed during pregnancy from January 2001 to September 2011 in Peking Union Medical College Hospital (PUMCH) was retrospectively studied. Clinical information, gestational age at diagnosis, treatment options and maternal and child outcomes were collected and analyzed. RESULTS: Thirteen patients out of 2030 cases of invasive cervical cancer were diagnosed during pregnancy with an incidence of 0.64% (13/2030). The Mean gestational age at diagnosis of 13 patients is 21(+6) weeks. Two cases were diagnosed during the first trimester, 8 cases at second trimester and 3 cases at third trimester respectively. Vaginal bleeding during the pregnancy was main clinical manifestation presented in 8 patients and all thirteen cases were diagnosed by biopsy with pathological types of squamous cell carcinoma in 10 cases. The International Federation of Gynecology and Obstetrics (FIGO) stage was I in eleven cases and stage II in two cases. Six patients of them received treatment promptly after diagnosis. The other 7 patients had delayed treatment with mean diagnosis-treatment interval time of 65 days due to fertility reasons, who ended pregnancy by cesarean section at mean gestational age of 34(+6) weeks, two of them received chemotherapy with cisplatin + fluorouracil (PF) or cisplatin respectively before the end of the pregnancy, while the one with PF chemotherapy experienced neonatal death. The rest 6 neonatal outcomes were good. As follow-up of 13 cases: 11 cases in stage I received surgical treatment, and two of which had recurrence respectively, 15 months and 7 months post surgery, and one case had died. One case of Stage II patients died and one had recurrence after 53 months after radiotherapy. The recurrence rate in 13 cases was 3/13 and the mortality rate was 2/13. CONCLUSIONS: Most cases of cervical cancer diagnosed during pregnancy were in early FIGO stage. For those patients diagnosed in late pregnancy with strong fertility demand, considering delayed treatment according to FIGO stage of the disease and fetus maturity is appropriate. Chemotherapy during pregnancy may cause neonatal complications.

[Identification of low-risk indicators of early stage cervical cancer].

OBJECTIVE: To explore the low-risk indicators of early cervical cancer. METHODS: The medical records of 201 patients undergoing radical surgery between March 2000 and April 2011 for staging Ia2,Ib1 (tumor diameter≤2cm) cervix cancer were retrospectively reviewed, with particular focus on the pathological findings [parametrial involvement, positive margin, positive pelvic lymph node, and lymph vascular space invasion (LVSI)], treatment, and outcomes. RESULTS: The operation duration ranged 75-330min (mean:188.87 min) and the intra-operative blood loss was approximately 100-2500 ml (mean: 583.33 ml). Pathology showed the rate of parametrial spread, positive margins, lymph node metastasis, LVSI was 0, 6.97%, 12.44%, and 17.41%. Based on the pathologic findings, the patients were classified as two groups: group A had 147 patients(73.13%) with no neoplasm or tumor diameter ≤2 cm,while group B had 54 patients (26.87%) with tumor diameter > 2 cm. The incidence of ≥ 1/2 cervical stromal invasion, LVSI, positive lymph node, underlying section of uterus involvement, and low tumor differentiation in group A and B were 20.14% vs. 85.19% (p = 0.000), 13.61% vs. 27.78%(p = 0.019), 9.52% vs. 20.37% (p=0.039), 4.82% vs. 14.81% (p=0.008), and 35.37% vs. 44.44% (p=0.025), respectively, with significant differences. Among the 163 patients who were followed up for more than 3 months, 10(6.13%) developed recurrence whereas no patient died. CONCLUSIONS: Pathologic parametrial involvement in clinical stage 1a2 and 1b1 cervical cancer is uncommon. Tumor size and cervical stromal invasion can be used to identify low-risk population that are worthy of consideration for studies of less radical surgery performed in conjunction with pelvic lymphadenectomy.