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To assess the actual clinical application of poly (adenosine diphosphate-ribose) polymerase inhibitor (PARPi) maintenance therapy in Chinese patients with recurrent ovarian cancer, and to explore prognostic factors associated with progression-free survival (PFS). We retrospectively assessed real-world clinical data from our hospital using the inclusion and exclusion criteria of representative randomized controlled trials, analyzed the prognosis, and performed univariate and multivariate analyses of prognostic factors. Between 2019 and 2022, the proportion of platinum-sensitive recurrence ovarian cancer patients who received PARPi maintenance therapy increased to 29.6%, 53.3%, 43.8% and 62.2%, respectively, each year. A total of 48 patients were included in the prognostic analysis, of which 32 and 16 received olaparib and niraparib, respectively. Using the criteria of the Study19 and SOLO2 studies, the olaparib group in our patients had coincidence rates of 56.3% and 18.8%, respectively. Using the criteria of the NOVA and NORA studies, the niraparib group had coincidence rates of 31.3% and 37.5%, respectively. Median PFS was 26.1 months (95% CI 20.2–32.1). Response to primary therapy was an independent prognostic factor for PFS (relative risk, 3.248; 95% CI 1.081–9.757, P = 0.036). PARPi maintenance therapy was also effective in real world applications. Complete response (CR) to primary therapy was an independent factor favorably affecting PFS. Therefore, primary treatment choices aimed at optimal cytoreduction during primary surgery and improving the CR rate should still be considered, which positively affects the long-term prognosis of patients in the new treatment mode. • From 2019 to 2022, the proportion of PSR maintenance therapy with PARPi increased from 29.6% to 62.2%. • There were substantial differences between the patients in actual clinical settings and the RCTs population. • The mPFS was 26.1 months in a real-world study regarding PARPi maintenance therapy in recurrent ovarian cancer patients. • CR to the primary therapy was the independent factor favorably affecting PFS in the new treatment mode. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to comprehensively analyze the clinical characteristics and treatment status of Chinese small cell carcinoma of the ovary hypercalcemic type (SCCOHT) patients, providing insights into this unique population and comparing findings with international literature., Methods: Through a meta-analysis, we collected data from published case reports and records from the Obstetrics & Gynecology Hospital of Fudan University. Demographic information, clinical presentations, tumor attributes, treatment modalities, and survival outcomes were extracted and examined alongside relevant global studies., Results: The analysis encompassed 80 Chinese SCCOHT patients, of which 62 from 33 previously reported literatures, and the other 18 were from Obstetrics & Gynecology Hospital of Fudan University. In 62 cases with stage information, A total of 25 tumors were International Federation of Gynecology and Obstetrics stage I, 3 were stage II, 19 were stage III, and 15 were stage IV. Most patients received surgery and chemotherapy, but regimens were varied. Median follow-up was 10 months (range=4-120). Elevated carbohydrate antigen 125 and serum calcium levels were consistent findings. Recurrence rates were notable, especially among stage I patients. Platinum-based chemotherapy, paclitaxel and carboplatin (n=11, 13.4%), constituted common treatment regimens., Conclusion: This study observed demographic and clinical similarities with international datasets. And the findings emphasize the urgency for innovative therapeutic approaches to improve outcomes in SCCOHT patients. Continued research efforts are essential to enhance the knowledge surrounding this rare malignancy and to optimize its clinical management., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2024. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Background: In China, secondary cytoreductive surgery (SCR) has been widely used in ovarian cancer (OC) over the past two decades. Although Gynecologic Oncology Group-0213 trial did not show its overall survival benefit in first relapsed patients, the questions on patient selection and effect of subsequent targeting therapy are still open. The preliminary data from our pre-SOC1 phase II study showed that selected patients with second relapse who never received SCR at recurrence may still benefit from surgery. Moreover, poly(ADP-ribose) polymerase inhibitors (PARPi) maintenance now has been a standard care for platinum sensitive relapsed OC. To our knowledge, no published or ongoing trial is trying to answer the question if patient can benefit from a potentially complete resection combined with PARPi maintenance in OC patients with secondary recurrence. Methods: SOC-3 is a multi-center, open, randomized, controlled, phase II trial of SCR followed by chemotherapy and niraparib maintenance vs chemotherapy and niraparib maintenance in patients with platinum-sensitive second relapsed OC who never received SCR at recurrence. To guarantee surgical quality, if the sites had no experience of participating in any OC-related surgical trials, the number of recurrent lesions evaluated by central-reviewed positron emission tomography-computed tomography image shouldn't be more than 3. Eligible patients are randomly assigned in a 1:1 ratio to receive either SCR followed by 6 cycles of platinum-based chemotherapy and niraparib maintenance or 6 cycles of platinum-based chemotherapy and niraparib maintenance alone. Patients who undergo at least 4 cycles of chemotherapy and must be, in the opinion of the investigator, without disease progression, will be assigned niraparib maintenance. Major inclusion criteria are secondary relapsed OC with a platinum-free interval of no less than 6 months and a possibly complete resection. Major exclusion criteria are borderline tumors and non-epithelial ovarian malignancies, received debulking surgery at recurrence and impossible to complete resection. The sample size is 96 patients. Primary endpoint is 12-month non-progression rate. [ABSTRACT FROM AUTHOR]

Objective: To investigate BRCA1 / 2 gene mutations and their relationship with clinicopathological features in patients with breast cancer in Zhoushan Islands., Methods: High-throughput whole-exome gene sequencing was used to detect BRCA1 / 2 mutations in 776 breast cancer patients in Zhoushan Islands., Results: The BRCA1 / 2 mutation rate of breast cancer patients in Zhoushan Islands was 4.38% (34/776). BRCA1 mutations were significantly correlated with age, molecular type, and family history of breast and ovarian cancers. BRCA2 mutations were most commonly found in invasive lobular carcinoma. Moreover, the BRCA2 mutation rate of cancers with molecular type luminal B (receptor protein-tyrosine kinase [HER2]-negative) was also relatively high., Conclusion: The rate of BRCA1 / 2 mutations in breast cancer patients from Zhoushan Islands is approximately 4.38%, and BRCA1 mutation is related to age, molecular type, and family history of breast and ovarian cancers., Competing Interests: Declaration of conflicting interestsThe authors declare that there is no conflict of interest.

Introduction: Female-specific cancers seriously affect physical and psychological health of women worldwide., Objectives: We aimed to elucidate trends in the age-standardized mortality rates (ASMRs) of breast cancer, cervical cancer, uterine cancer, and ovarian cancer in female populations with different socioeconomic statuses in China and in countries with different Human Development Index (HDI)., Methods: A longitudinal study was performed using the data of cancer death in China and other 39 countries. The mortality rates were standardized with the Segi's world population. Trends in the mortalities were exhibited by estimated annual percentage change (EAPC). Pearson correlation was used to assess the association between EAPC and HDI., Results: In mainland China, female breast cancer, cervical cancer, uterine cancer, and ovarian cancer accounted for 6.60 %, 4.21 %, 2.50 %, and 2.02 % of cancer death (n = 1,314,040) in women with 1,220,251,032 person-years, respectively. The ASMRs of cervical cancer (EAPC = 3.87 %, P < 0.001) and ovarian cancer (EAPC = 1.81 %, P < 0.001) increased, that of female breast cancer unchanged, whereas that of uterine cancer was extremely higher and rapidly decreased (EAPC =  - 7.65 %, P < 0.001), during 2004-2019. The ASMRs of female breast and ovarian cancers were higher in urban and developed regions than in rural and undeveloped regions, in contrast to cervical and uterine cancers. The ASMRs of female breast and ovarian cancers were lower in China than in other countries, in contrast to uterine cancer. The ASMR of cervical cancer decreased, that of uterine cancer increased, in other countries during 2004-2017. EAPCs for the ASMRs of breast and ovarian cancers were inversely correlated to HDI., Conclusion: The ASMRs of cervical and ovarian cancers increased, in contrast to uterine cancer, in China during socioeconomic transition. Trends in the ASMRs of breast and ovarian cancers were inversely associated with HDI. These data help control female-specific cancers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Production and hosting by Elsevier B.V.)

Background: Gynecological cancer will become a more important public health problem in future years but limited evidence on gynecological cancer burden in China., Methods: We extracted age-specific rate of cancer cases and deaths during 2007-2016 from the Chinese Cancer Registry Annual Report, and estimated age-specific population size using the data released by National Bureau of Statistics of China. Cancer burden were calculated by multiplying the rates with the population size. Temporal trends of the cancer cases, incidence, deaths, and mortality during 2007-2016 were calculated by JoinPoint Regression Program, and from 2017 to 2030 were projected by grey prediction model GM (1,1)., Results: In China, total gynecological cancer cases increased from 177,839 to 241,800, with the average annual percentage change of 3.5% (95% CI: 2.7-4.3%) during 2007-2016. Cervical, uterine, ovarian, vulva, and other gynecological cancer cases increased by 4.1% (95% CI: 3.3-4.9%), 3.3% (95% CI: 2.6-4.1%), 2.4% (95% CI: 1.4-3.5%), 4.4% (95% CI: 2.5-6.4%), and 3.6% (95% CI: 1.4-5.9%) respectively. From 2017 to 2030, projected gynecological cancer cases are changing from 246,581 to 408,314. Cervical, vulva and vaginal cancers showed evident upward trend, while uterine and ovarian cancer cases are slightly increasing. The increases for age-standardized incidence rates were similar with that of cancer cases. Temporal trends of cancer deaths and mortality were similar with that of cancer cases and incidence during 2007-2030, except that uterine cancer deaths and mortality were declined., Conclusions: With the aging of population and other increased risk factors, the burden of gynecological cancers in China is likely to be grew rapidly in the future, comprehensive gynecological cancer control should be concerned., (© 2023. The Author(s).)

A chemical investigation of the Chinese liverwort Chandonanthus birmensis Steph identified five undescribed cembrane-type diterpenoids, together with six known cembrane diterpenes, one fusicoccane-type diterpenoid, and a dolabellane-type diterpenoid. Their structures were established by comprehensive analysis of HRESIMS, NMR spectroscopic data, electronic circular dichroism (ECD) calculations and single-crystal X-ray diffraction analysis. Cytotoxicity tests of the isolated diterpenoids against five cancer cell lines (A2780, A549, H460, H460RT, and HeLa) revealed that several compounds showed moderate inhibitory effects with IC 50 values ranging from 11.1 to 36.2 μM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

This study aimed to establish a prognosis-prediction model based on serological indicators in patients with epithelial ovarian cancer (EOC). Patients initially diagnosed as ovarian cancer and surgically treated in Fudan University Shanghai Cancer Center from 2014 to 2018 were consecutively enrolled. Serological indicators preoperatively were collected. A risk model score (RMS) was constructed based on the levels of serological indicators determined by receiver operating characteristic curves. We correlated this RMS with EOC patients’ overall survival (OS). Finally, 635 patients were identified. Pearson’s χ2 results showed that RMS was significantly related to clinical parameters. Kaplan−Meier analysis demonstrated that an RMS less than 3 correlated with a longer OS (p < 0.0001). Specifically, significant differences were perceived in the survival curves of different subgroups. Multivariate Cox analysis revealed that age (p = 0.015), FIGO stage (p = 0.006), ascites (p = 0.015) and RMS (p = 0.005) were independent risk factors for OS. Moreover, RMS combined with age, FIGO and ascites could better evaluate for patients’ prognosis in DCA analyses. Our novel RMS-guided classification preoperatively identified the prognostic subgroups of patients with EOC and showed higher accuracy than the conventional method, meaning that it could be a useful and economical tool for tailored monitoring and/or therapy.

Purpose: The application of menopausal hormone therapy (MHT) is generally restricted most likely due to limited prescriptions by doctors. Fear of cancer risk may be a critical factor. We investigated the views of Chinese obstetricians and gynecologists on the relationship between hormone therapy and cancer risk., Methods: A self-administered web-based nationwide cross-sectional questionnaire., Results: In total, 5243 medical workers responded to the questionnaire (response rate 94.5%); 4995 were certified obstetricians and gynecologists. Most were aged 36-55 years (70.9%), had > 10 years of working experience (68.5%), and worked at tertiary (34.8%) and secondary hospitals (49.1%); 70% of the clinicians were aware of the endometrial cancer risk caused by estrogen, and 20% considered progestogen to cause the same risk. Regarding breast cancer, while 67.9 and 74.8% of the clinicians viewed natural and synthetic estrogens as risk factors, respectively, only 41.7% identified the carcinogenic effect of progestins as higher than that of progesterone (26.7%). Approximately 75% of the participants believed synthetic estrogens and progestins constituted a risk for ovarian cancer (higher than the percentages for their natural counterparts); 13.0-21.1% of the respondents were worried about choriocarcinoma due to hormone treatment. Finally, 86.8% of obstetricians and gynecologists claimed to have poor knowledge regarding this field., Conclusion: Misconceptions and a lack of knowledge in this regard may result in the fear of cancer and could be the underlying causes of limited MHT prescriptions. We believe that scientific research, continued education, and the media all have roles to play in changing preconceived ideas regarding MHT prescriptions., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Yolk sac tumors (YSTs) are a major histological subtype of malignant ovarian germ cell tumors with a relatively poor prognosis. The molecular basis of this disease has not been thoroughly characterized at the genomic level. Here we perform whole-exome and RNA sequencing on 41 clinical tumor samples from 30 YST patients, with distinct responses to cisplatin-based chemotherapy. We show that microsatellite instability status and mutational signatures are informative of chemoresistance. We identify somatic driver candidates, including significantly mutated genes KRAS and KIT and copy-number alteration drivers, including deleted ARID1A and PARK2, and amplified ZNF217, CDKN1B, and KRAS. YSTs have very infrequent TP53 mutations, whereas the tumors from patients with abnormal gonadal development contain both KRAS and TP53 mutations. We further reveal a role of OVOL2 overexpression in YST resistance to cisplatin. This study lays a critical foundation for understanding key molecular aberrations in YSTs and developing related therapeutic strategies.

Purpose: As a kind of secondary tumor of the ovary, ovarian metastasis from colorectal cancer (OMCRC) happens rarely. Prognostic factors of OMCRC are still undetermined. This study was conducted to analyze clinical characteristics and prognostic factors of OMCRC patients., Methods: Data of patients with OMCRC were collected retrospectively from four large-capacity hospitals in China. Kaplan-Meier method was applied to estimate disease-specific overall survival (OS), and multivariate Cox regression analysis was used to identify prognostic factors. A novel nomogram was developed to estimate individual survival probability, whose performance was internally validated using concordance index (C-index) and calibration curve., Results: Totally, 162 cases were eligible, with a median age at diagnosis of 49 years old. The median size of ovarian metastases was 9.0 cm (95% CI: 8.5-10.4 cm). 93.8% of patients received surgery of ovarian metastases. Median time from CRC diagnosis to metachronous ovarian metastasis was 13.0 months (95% CI: 13.5-17.7 months). Median OS after ovarian metastasis diagnosis was 26.0 months (95% CI: 22.3-29.7 months). Integrating univariate and multivariate analyses, eight factors (including age, menopausal status, primary tumor location, N stage of primary tumor, surgery of primary tumor, differentiation grade, bilateral metastasis, and systemic chemotherapy) were used to develop a novel nomogram, with a C-index of 0.65 (95% CI: 0.595-0.705). Calibration curves indicated relatively good agreement between predicted and actual survival., Conclusions: This nomogram could be a promising tool to help clinicians to estimate individual survival outcome of patients with OMCRC. Further study is warranted to validate the practicality of this model.

Objective: To describe Chinese Lynch syndrome-associated colorectal cancer patients' self-concept and adherence to surveillance and explore the factors influencing patients' adherence to surveillance., Methods: This was a cross-sectional quantitative study of a group of 83 Lynch syndrome-associated colorectal cancer patients, using the Lynch syndrome self-concept scale and medical records. IBM SPSS 20.0 was used for statistical analysis., Results: Patients' adherence to surveillance, for colorectal cancer, gastric cancer and small intestinal cancer, endometrial and ovarian cancer, they were 93.2%, 41.8% and 56.7% respectively. Older patients had lower surveillance adherence of colorectal cancer, gastric cancer and small intestinal cancer than younger patients (p < 0.05). Occupation was the major factor influencing their surveillance adherence of endometrial and ovarian cancer (p < 0.05). The score for Lynch syndrome self-concept was 72.23 ± 25.65., Conclusion: The surveillance adherence of patients is high for colorectal cancer but low for extracolorectal cancers. Low surveillance adherence is associated with old age, living with family members and less secure employment. Chinese patients' self-concept scores were slightly higher than foreign patients. Nurses should pay more attention to the surveillance adherence and self-concept of Lynch syndrome-associated colorectal cancer patients and develop effective interventions to improve their surveillance adherence., (© 2020 John Wiley & Sons Ltd.)

Background: Choriocarcinoma is a rare malignant neoplasm, which is classified as either gestational choriocarcinoma or nongestational choriocarcinoma. The purpose of this study was to examine the clinical characteristics of Chinese female nongestational choriocarcinoma patients and discuss our experience in treating this rare disease., Results: We conducted a single-center retrospective study on a sample of 37 nongestational choriocarcinoma patients who were diagnosed and treated at Peking Union Medical College Hospital from March 1982 to March 2020. Their demographic, clinical, laboratory, and therapeutic data were collected. Detailed information was available for all 37 individuals in our sample. The primary lesions included 34 in the ovaries, 2 in the pituitary and 1 in the stomach. The median age of onset was 22 years, and the median follow-up period spanned 41 months. The lungs (40.5%) were the most commonly observed metastatic site. All subjects were treated with surgery and multidrug chemotherapies, and a median of 4.0 courses was required to achieve complete remission. The overall complete response rate, relapse rate, and 3-year and 5-year survival rates were 81.1%, 16.7%, 80.0%, and 75.5%, respectively., Conclusions: Nongestational choriocarcinoma can be managed well using surgery and multidrug chemotherapies, but the overall outcome of nongestational choriocarcinoma is still worse than that of gestational choriocarcinoma. Mixed nongestational choriocarcinoma seems to have similar therapeutic outcomes as pure tumors.

Background: Human epididymis secretory protein 4 (HE4) is a new ovarian cancer biomarker. The factors influencing HE4 levels are not clear, and the reference data in China are limited. Here, we aim to evaluate the effects of menopause and age on HE4 levels and to provide a possible reference value for HE4 in healthy Chinese people., Methods: A total of 2493 healthy females aged 40 years or older were recruited from March 2013 to March 2017 with the cooperation of four medical institutions across Beijing, China. The serum levels of HE4 and cancer antigen 125 (CA125) were measured by enzyme-linked immunosorbent assay. The Wilcoxon rank-sum test of variance and a stratified analysis were used to analyze the relationships among age, menopausal status, and levels of HE4 or CA125. Confidence intervals (5%-95%) were determined for reference ranges in different populations., Results: There was a statistically significant difference in median HE4 levels between the post-menopausal (n = 2168) and pre-menopausal groups (n = 325) (36.46 vs. 24.04 pmol/L, Z = -14.41, P < 0.001). HE4 increased significantly with age in the post-menopausal groups (H = 408.18, P < 0.001) but not in the pre-menopausal subjects (Z = -0.43, P = 0.67). The upper 95th percentile of HE4 levels were 44.63 pmol/L for pre-menopausal women, 78.17 pmol/L for post-menopausal women, and 73.3 pmol/L for all women. In the post-menopausal population, the HE4 reference ranges were 13.15 to 47.31, 14.31 to 58.04, 17.06 to 73.51, 24.50 to 115.25, and 35.71 to 212.37 pmol/L for different age groups from forty divided by decade. The CA125 level was affected mainly by menopausal status and not age., Conclusions: Menopausal status and age were both important factors influencing the level of HE4, and age affected HE4 levels mainly in post-menopausal women. The HE4 level was higher in the post-menopausal population than in the pre-menopausal population and increased with age.

Objective: To investigate DICER1 hotspot mutations in ovarian Sertoli-Leydig cell tumor (SLCT) and its associated clinicopathological features. Methods: Forty-three SLCTs and 40 other sex cord-stromal tumors (SCSTs) diagnosed between 2010 and 2017 at Fudan University Shanghai Cancer Center were examined for somatic DICER1 hotspot mutations by Sanger sequencing. The associations between mutation status and clinicopathological features, including patient age, tumor differentiation and recurrence, were analyzed. Results: Somatic DICER1 mutations were found in 51% (22/43) of SLCTs, while none in the other 40 SCSTs. The most common mutation of DICER1 was p.D1709N in exon 24 (41%, 9/22) and the second most common mutation of DICER1 was p.E1813K in exon 25 (14%, 3/22). A novel frameshift mutation (c.5464delG, p.M1837fs*16) was identified in one SLCT with microcystic pattern. Mutations were more likely to occur in patients under forty years of age ( P= 0.046), whereas no significant associations were found between DICER1 mutations and clinical symptoms, morphology or tumor recurrence. Conclusions: Somatic DCIER1 hotspot mutations are specifically found in SLCT and may serve as an ancillary marker in differential diagnosis of SLCT from other SCST. The mutations occur more often in young patients (<40 years old). Additional studies are warranted to examine the associations between DICER1 mutations and clinicopathological features and prognosis of SLCT.

Background: In China, secondary cytoreductive surgery (SCR) has been widely used in ovarian cancer (OC) over the past two decades. Although Gynecologic Oncology Group-0213 trial did not show its overall survival benefit in first relapsed patients, the questions on patient selection and effect of subsequent targeting therapy are still open. The preliminary data from our pre-SOC1 phase II study showed that selected patients with second relapse who never received SCR at recurrence may still benefit from surgery. Moreover, poly(ADP-ribose) polymerase inhibitors (PARPi) maintenance now has been a standard care for platinum sensitive relapsed OC. To our knowledge, no published or ongoing trial is trying to answer the question if patient can benefit from a potentially complete resection combined with PARPi maintenance in OC patients with secondary recurrence., Methods: SOC-3 is a multi-center, open, randomized, controlled, phase II trial of SCR followed by chemotherapy and niraparib maintenance vs chemotherapy and niraparib maintenance in patients with platinum-sensitive second relapsed OC who never received SCR at recurrence. To guarantee surgical quality, if the sites had no experience of participating in any OC-related surgical trials, the number of recurrent lesions evaluated by central-reviewed positron emission tomography-computed tomography image shouldn't be more than 3. Eligible patients are randomly assigned in a 1:1 ratio to receive either SCR followed by 6 cycles of platinum-based chemotherapy and niraparib maintenance or 6 cycles of platinum-based chemotherapy and niraparib maintenance alone. Patients who undergo at least 4 cycles of chemotherapy and must be, in the opinion of the investigator, without disease progression, will be assigned niraparib maintenance. Major inclusion criteria are secondary relapsed OC with a platinum-free interval of no less than 6 months and a possibly complete resection. Major exclusion criteria are borderline tumors and non-epithelial ovarian malignancies, received debulking surgery at recurrence and impossible to complete resection. The sample size is 96 patients. Primary endpoint is 12-month non-progression rate., Trial Registration: ClinicalTrials.gov Identifier: NCT03983226., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2020. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.)

Objective: Data on the treatment of patients with ovarian cancer (OC) and associated cerebral infarction (CI) are extremely limited. The objectives were to investigate the risk factors for prognosis in patients with OC and associated CI., Methods: We retrospectively reviewed the electronic medical records of patients with OC from January 2013 to November 2018 in Peking Union Medical Hospital., Results: In total, 2632 inpatients were diagnosed with malignant ovarian cancer in our institution, and 30 patients (1.1%) were diagnosed with OC-associated CI. The median age was 60 years (range, 37-83). The standard treatment, according to National Comprehensive Cancer Network (NCCN) guidelines, was administered to 19 patients. The median follow-up time was 19.5 months (range, 1-59 months). In total, 17 patients experienced tumor progression, and 16 of them died. In univariate analysis, overall survival was significantly associated with the D-dimer level (P=0.017), FIGO stage (P=0.014), complete cytoreduction (P<0.000) and standard treatment (P<0.000). In multivariate analysis, the standard treatment remained an independent protective factor for death (hazard ratio=0.061, 95% confidence interval=0.007-0.537, P=0.012)., Conclusion: Although the prognosis of patients with OC and associated CI was poor, those who underwent the standard treatment still benefited., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Yuan et al.)

Objective: To investigate the clinicopathological characteristics and significance of solid, endometrioid and transitional (SET) ovarian high-grade serous carcinoma (HGSC). Methods: A total of 408 cases of ovarian HGSC admitted to Peking University People's Hospital from January 2011 to September 2016 were collected. (1) According to the proportion of tumors with SET form in all tumors, they were divided into three groups: HGSC-classic group (<25%), HGSC-SET Ⅰ (25%-50%) and HGSC-SET Ⅱ (>50%) group. The clinical and pathological characteristics of three groups of ovarian HGSC patients were compared respectively. (2) According to the growth pattern, that was, the proportion of pushing/expanding invasive tumors in the whole pelvic disseminated tumors of pelvic disseminated tumors, the three groups were divided into four subgroups: group A (0-25%), group B (26%-50%), group C (51%-75%) and group D (>75%). Differences in progression-free survival (PFS) among the four subgroups in each group were compared respectively. Results: The median age of 408 cases with ovarian HGSC was 63.3 years (47-78 years), including 152 cases premenopausal and 256 cases postmenopausal. Among 408 cases of ovarian HGSC, 290 cases were in HGSC-classic group, 91 cases in HGSC-SET Ⅰ and 27 cases in HGSC-SET Ⅱ group. (1) There were significant differences in age, proportion of menopausal patients, tumor necrosis (including map necrosis or acne necrosis), response rate to primary chemotherapy, 5-year mortality rate and PFS between HGSC-SET Ⅰ and HGSC-SET Ⅱ ( P <0.05). There was no significant difference among the above indexes between HGSC-SET Ⅰ and HGSC-SET Ⅱ ( P >0.05). In HGSC-classic group, HGSC-SET Ⅰ and HGSC-SET Ⅱ, the proportion of family members or patients with history of epithelial ovarian cancer or breast cancer increased in turn, and the detection rate of serous tutal intraepithelial carcinoma (STIC) in fallopian tube tissue decreased in turn. There were significant differences between the two groups ( P <0.05). (2) In HGSC-classic group, there were 147 cases in group A, 124 cases in group B and 19 cases in group C (0 case in group D), with median PFS of 17.4, 17.7 and 16.5 months respectively ( P <0.05); 10, 6, 29 and 46 cases in group A, B, C and D in HGSC-SET Ⅰ, with median PFS of 9.6, 12.7, 30.1 months and 39.0 months respectively, which there were significant difference among group A and C and D (all P <0.05); among group B, C and D group in HGSC-SET Ⅱ, there were respectively 3, 12 and 12 cases (0 case in group A), and the median PFS was 13.5, 34.2 and 47.8 months ( P <0.05). PFS was positively correlated with the increase of push/expansive infiltration ratio. Conclusions: The detection rate of STIC in ovarian HGSC patients with SET is higher, the effect of primary chemotherapy is better, and PFS is prolonged. PFS was significantly prolonged in patients with pelvic disseminated tumors of HGSC-SET, the infiltration of which were predominated by pushing or expanding boarder.

Objective: To compare intratumoral tumor-infiltrating lymphocytes (TIL) in a cohort of high-grade serous ovarian carcinoma patients between those who treated with neoadjuvant chemotherapy (NACT) and primary debulking surgery (PDS), and to determine the clinical and prognostic significance of TIL in high-grade serous ovarian carcinoma. Methods: Tissue microarrays and immunohistochemistry were used to assess the quantity of CD3+, CD4+ and CD8+ lymphocytes in tumor tissue from 138 high-grade serous ovarian carcinoma (PDS n= 84, NACT n= 54) which were collected from January 2013 to January 2016 at West China Second University Hospital, Sichuan University. TIL was analysed in two predefined groups of low and high TIL. The associations between clinical features and TIL were evaluated by χ(2) test or Fisher's exact test, and Kaplan-Meier survival analysis and Cox proportional hazards regression model were used for the association between the amounts of TIL and progression free survival. Results: There was no difference in TIL/HPF (high-power field) counting in tumor tissue between PDS and NACT ( P> 0.05), and in the PDS cohort, CD3+, CD4+ and CD8+TIL were not associated with any clinical features like age, FIGO stage, tumor size and chemotherapy sensitivity, however, in the NACT cohort, CD8+TIL was strongly associated with chemotherapy sensitivity. The univariable analysis supported that high CD8+TIL in tumor tissue was associated with longer progression free survival both in the PDS and NACT cohort( P= 0.030, P= 0.032), but not CD4+TIL, in the NACT cohort, high CD3+TIL were also associated with longer progression free survival ( P= 0.019). Finally, in multivariate analysis, only the high CD8+TIL had prognostic significance ( HR= 0.369, 95 %CI =0.176-0.772, P= 0.008). Conclusion: High CD8+lymphocytes density in tumor tissue was significantly associated with improved progression free survival in high-grade serous ovarian carcinoma. Besides, the CD8+lymphocytes density could be served as a potential marker of the chemotherapy sensitivity in patients who treated with neoadjuvant chemotherapy.

Objective: To assess the expression level of targeting drug-based molecular biomarkers in ovarian clear cell carcinoma (OCCC) tissues and its clinical significance. Methods: A total of 63 OCCC patients included 40 primary OCCC and 23 recurrent OCCC for secondary cytoreductive surgery (SCS), who had received primary surgeries at Fudan University Shanghai Cancer Center between January, 2008 and December, 2015 were enrolled, and immunohistochemistry SP method was used to test human epidermal growth factor receptor (EGFR), human epidermal growth factor receptor-2 (HER2), aurora kinase A (AURKA), breast cancer susceptibility gene 1 (BRCA1), BRCA2 and programmed death-ligand 1 (PD-L1)protein expression in paraffin-embedded tissues. Results: The positive rates of EGFR, HER2, AURKA,BRCA1, BRCA2 and PD-L1 in primary and recurrent tumor tissues were respectively 20% (8/40) vs 30% (7/23) , 22% (9/40) vs 35% (8/23) , 38% (15/40) vs 35% (8/23) , 42% (17/40) vs 39% (9/23) , 20% (8/40) vs 22% (5/23) , 25% (10/40) vs 17% (4/23) , and there were no significant differences between primary and recurrent OCCC (all P> 0.05). χ(2)-test or Fisher exact analysis revealed that HER2 expression in recurrent tumor tissues had a relationship with chemoresistance ( P< 0.05), while the expression of other biomarkers showed no significant relationship with chemoresistance (all P> 0.05). Further, Kaplan-Meier survival analysis showed that patients with HER2 and AURKA-positive expression had a significantly shorter progression-free survival time in primary OCCC (4 months vs 10 months, log-rank test, P< 0.05 for HER2; and 4 months vs 10 months, P< 0.05 for AURKA); and a shorter overall survival time after SCS in recurrent OCCC (10 months vs 44 months, P< 0.05 for HER2; and 13 months vs 43 months, P< 0.05 for AURKA). However, multivariate Cox proportional hazards regression analysis indicated that none of these 6 biomarkers was independent risk factor of progression-free survival time of primary OCCC or overall survival time after SCS for recurrent OCCC ( P> 0.05). Conclusion: HER2 and AURKA could serve as prognostic factors in ovarian clear cell carcinoma.

Objective: To explore the origin of ovarian high grade serous carcinoma (HGSC) through analysing the expression and significance of PAX8, PAX2, p53 and RAS in the ovary and fallopian tube of different types and grades of serous carcinoma. Methods: A total of 44 cases tissue samples of ovarian tumor including 34 malignant ovarian tumor and 10 normal normal tissue (as control group) were collected from the admitted patients in Affiliated Tumor Hospital of Guangxi Medical University from January 2015 to January 2016. Fallopian tube tissues were segmented in accordance with the fimbria, ampulla, isthmus and the corresponding ovarian tissues were by the side. There were 34 cases of patients with ovarian cancer including 29 cases of epithelial ovarian cancer (27 serous carcinoma, 1 mucinous carcinoma,1 endometrioid adenocarcinoma) and 5 non-epithelial ovarian cancer (sex cord-interstitial tumor). Among 27 cases of patients with ovarian serous cancer, there were 23 HGSC and 4 low-grade ovarian serous cancer (LGSC). One hundred fifty-three cases of samples were diagnosed as ovarian serous cancer by Shandong University Affiliated Qilu Hospital from 2005 to 2013 and these samples were made tissue microarray. (1) To analyze the expression and differences of PAX8, PAX2, p53 and RAS in the above tissues and tissue microarray from ovarian and tubal of HGSC and control women by immunohistochemistry methods. (2) To compare the expression levels of PAX8, PAX2, p53 and RAS in ovarian and fallopian tubes of ovarian cancer patients with different pathological types. (3) To analyze the correlations of tubal and ovarian tissue in PAX8, PAX2, p53 and RAS expression of HGSC. (4) To analyze the factors of the prognosis of ovarian serous cancer in tissue microarray by single factor analysis method. Results: (1) PAX8, PAX2, p53 and RAS expression was negative in normal ovarian epithelium of control group, but the expression of PAX8, PAX2, p53 and RAS were strongly positive brown in secrete cells of normal fallopian tube epithelium. (2) p53 and RAS expression of fallopian tube epithelium in the epithelial ovarian cancer group were significantly higher than those in the non-epithelial ovarian cancer groups ( P< 0.05), but the expression of PAX8 and PAX2 in fallopian tube and the expression of PAX8, PAX2, p53 and RAS in ovarian tissue was not statistically significant in the groups ( P> 0.05). PAX8, PAX2 and p53 expression of the ovarian in HGSC group were significantly higher than those in LGSC group ( P< 0.05), while the expression of RAS was lower in the ovarian of the high-grade group ( P< 0.05), while the expression of PAX8, PAX2, p53 and RAS in fallopian tube was not statistically significant in the groups ( P> 0.05). (3) There was a significantly positive correlation between fallopian tube and the corresponding ovary of HGSC in PAX8 and PAX2 expression ( r= 0.422, P= 0.045; r= 0.693, P= 0.000), but not correlation in p53 and RAS expression ( r= 0.058, P= 0.793; r= - 0.190, P= 0.384). (4) Univariate survival analysis showed that the progression free survival time in patients with ovarian serous cancer group was significantly correlated with the protein expression of PAX8, PAX2 and RAS ( P< 0.05), but there were not correlated with age, surgical staging, cell differentiation, lymph node metastasis and preoperative chemotherapy and p53 protein expression ( P> 0.05). The total survival time in patients with ovarian serous cancer group was significantly correlated with the protein expression of PAX8 ( P< 0.05), but there were not correlated with age,surgical staging, cell differentiation, lymph node metastasis and preoperative chemotherapy and the protein expression of PAX2, RAS and p53 ( P> 0.05). Conclusions: PAX8, PAX2, p53, RAS are of great significance for the study of origin of HGSC. HGSC may be derived from fallopian tube, but further investigation would be necessary to confirm this. PAX8, PAX2, p53, RAS could be expected to be used as predictors of survival prognosis in patients with ovarian serous cancer.

Objective: To explore how to reduce the incidence of pelvic mass after hysterectomy, and to evaluate clinical characteristics and the risks. Methods: A retrospective study was carried out in 85 patients who returned for surgery due to a pelvic mass after prior hysterectomy for benign disease at Peking Union Medical College Hospital from January 2011 to June 2016. Results: The majority of pelvic masses arising after hysterectomy and requiring surgery were benign (74%, 63/85), while 19% (16/85) were malignant and 7% (6/85) were borderline. The most common type was ovarian endometrioma (24%, 20/85) which usually occurs within the 5 years (16 cases), however, ovarian tumors (18 cases) were more likely to occur ≥10 years after hysterectomy. Characteristics associated with significantly increased likelihood of ovarian endometrioma were mainly ascribed to younger age [(47±5) years old], prior presence of endometriosis or adenomyosis (65%, 13/20) and shorter time to pelvic mass onset [(3±3) years], as opposed to ovarian tumors (all P <0.01). Additionally, higher number of prior abdominal surgeries significantly intensified the risk ( RR= 9.410, 95% CI: 1.099-80.564, P =0.041). Conclusions: The occurrence of pelvic mass after hysterectomy is tightly related to prior histologic findings, and particularly for ovarian endometrioma. Higher number of prior abdominal surgery will exacerbated the risk. It is effective to prevent the pelvic mass in women after hysterectomy if treat patients for the purpose of the risk factors.

Objectives: To explore the expression level of membrane-associated protein Numb in epithelial ovarian carcinoma and its relationship with ovarian cancer stem cell markers CD117,CD133,acetaldehyde dehydrogenase 1(ALDH1)., Methods: A total of 136 patients who had ovarian tumors and 22 patients who had not ovarian tumors in Department of Gynaecology and Obstetrics,West China Second University Hospital,Sichuan University were chosen as the study subjects.According to the histopathologic examination results,they were divided into epithelial ovarian carcinoma group ( n =92),ovarian borderline tumor group ( n =23),ovarian benign tumor group ( n =21) and normal ovary group ( n =22).Expression levels of Numb protein,CD117,CD133 and ALDH1 in ovarian tissue were detected by immunohistochemical SP method and these several kinds of protein expression differences and correlation statistical analysis were performend., Results: 1 The positive expression rate of Numb protein in epithelial ovarian carcinoma group was higher than that in benign tumor or normal ovary group,also Numb protein positive expression rate in ovarian borderline tumor group was higher than that in normal ovary group,and the differences were statistically significant ( P <0.05).2 Numb protein positive expression rate in ovarian tissue in patients with epithelial ovarian carcinoma FIGO stage1-2 was lower than that in stage 3-4,also the same in no lymph nodes metastasis compared with lymph nodes invasion,and the differences of positive expression rate were statistically significant ( P <0.05).While there were no significant differences among different age,histopathological types,pathological grades and residual tumor size ( P >0.05).3 There was no correlation between Numb protein and CD117 and CD133 positive expression rate in epithelial ovarian carcinoma tissue [correlation coefficient ( r )=0.116, P =0.261; r =0.083, P =0.425].However,the positive expression rate of Numb protein and ALDH1 was positively correlated ( r =0.296, P =0.261)., Conclusions: The expression of Numb protein may involve in the occurrence,invasion and mechanisms of ovarian cancer,positively correlated with ovarian cancer stem cell markers ALDH1,and may affect the prognosis of patients.

Objective: To provide reference information for prognosis and control of female cancers by analyzing survival rates of breast, cervical and ovarian cancer patients during 2005-2010 in Zhejiang province., Methods: The morbidity and mortality data of 18 133 breast, cervical and ovarian cancer patients whose information were registered in health surveillance zone during 2005-2010 in Zhejiang were analyzed. The December 31(st), 2012 was set as the deadline of survival time. Observed survival rate (OS) and relative survival rate (RS) were calculated using SURV3.01 software and comparison between survival rates was conducted through Hakulinen's likely hood ratio test., Results: The 5-year OS of breast cancer, cervical cancer, and ovarian cancer were 76.89%, 70.79%, 2.59%, respectively during 2005-2010 in Zhejiang province. The 5-year RS of the three cancers were 80.26%, 73.89%, 55.17%, respectively. The 5-year RS of breast cancer, cervical cancer, and ovarian cancer in urban area were 83.11%, 77.87%, and 57.22% and 78.00%, 72.21%, and 53.83% in rural areas, respectively. The overall RS of urban patients was higher than the rural's (χ(2) = 24.98, 11.55 and 6.62, respectively, all P values < 0.05). The 5-year RS of breast cancer, which was grouped by age, showed that the 15-44 years group was the highest (83.40%), while 65-77 years group was the lowest (74.67%). The 5-year RS of cervical cancer decreased with age, with a 41.73% decrease from 83.83% (15-44 years group) to 42.10% ( ≥ 75 years group). The 15-44 years group showed the highest 5-year RS of ovarian cancer (74.30%), while ≥ 75 years group was the lowest (41.80%)., Conclusion: The prognosis of breast cancer and cervical cancer were relatively optimistic, while the ovarian cancer was not. The prognosis of female cancer patients in urban areas were better than in rural areas.

Bioassay-directed fractionation of extract of Arnebia euchroma led to the isolation of alkannin (1), shikonin (2), and their derivatives (3-8) as the active principles against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). The stereochemistry of alpha-methylbutyryl alkannin (8) is revealed for the first time, and the antimicrobial activity of 8 was compared with its corresponding diastereomer (9). The derivatives 3-9 showed stronger anti-MRSA activity [minimum inhibitory concentrations (MICs) ranged from 1.56 to 3.13 microg/mL] than alkannin or shikonin (MIC = 6.25 microg/mL). Anti-MRSA activity of derivatives was bactericidal with minimum bactericidal concentration (MBC)/MIC < or = 2. In a time-kill assay, the bactericidal activity against MRSA was achieved as rapidly as 2 h. The derivatives 3-9 were also active against vancomycin-resistant Enterococcus faecium (F935) and vancomycin-resistant Enterococcus faecalis (CKU-17) with MICs similar to those with MRSA. Aromatic ester derivatives were also synthesized for antimicrobial activity comparison. None of these compounds were active against Gram-negative bacteria tested. Their cytotoxicity was also evaluated on selected cancer cell lines, and they expressed their activity in the range 0.6-5.4 microg/mL (CD(50)). Our results indicate that the ester derivatives of alkannin are potential candidates of anti-MRSA and anti-VRE agents with antitumor activity.