Exploratory biomarker analysis in the phase III L-MOCA study of olaparib maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer.

BACKGROUND: The prospective phase III multi-centre L-MOCA trial (NCT03534453) has demonstrated the encouraging efficacy and manageable safety profile of olaparib maintenance therapy in the Asian (mainly Chinese) patients with platinum-sensitive relapsed ovarian cancer (PSROC). In this study, we report the preplanned exploratory biomarker analysis of the L-MOCA trial, which investigated the effects of homologous recombination deficiency (HRD) and programmed cell death ligand 1 (PD-L1) expression on olaparib efficacy. METHODS: HRD status was determined using the ACTHRD assay, an enrichment-based targeted next-generation sequencing assay. PD-L1 expression was assessed by SP263 immunohistochemistry assay. PD-L1 expression positivity was defined by the PD-L1 expression on ≥ 1% of immune cells. Kaplan-Meier method was utilised to analyse progression-free survival (PFS). RESULTS: This exploratory biomarker analysis included 225 patients and tested HRD status [N = 190; positive, N = 125 (65.8%)], PD-L1 expression [N = 196; positive, N = 56 (28.6%)], and BRCA1/2 mutation status (N = 219). The HRD-positive patients displayed greater median PFS than the HRD-negative patients [17.9 months (95% CI: 14.5-22.1) versus 9.2 months (95% CI: 7.5-13.8)]. PD-L1 was predominantly expressed on immune cells. Positive PD-L1 expression on immune cells was associated with shortened median PFS in the patients with germline BRCA1/2 mutations [14.5 months (95% CI: 7.4-18.2) versus 22.2 months (95% CI: 18.3-NA)]. Conversely, positive PD-L1 expression on immune cells was associated with prolonged median PFS in the patients with wild-type BRCA1/2 [20.9 months (95% CI: 13.9-NA) versus 8.3 months (95% CI: 6.7-13.8)]. CONCLUSIONS: HRD remained an effective biomarker for enhanced olaparib efficacy in the Asian patients with PSROC. Positive PD-L1 expression was associated with decreased olaparib efficacy in the patients with germline BRCA1/2 mutations but associated with improved olaparib efficacy in the patients with wild-type BRCA1/2. TRIAL REGISTRATION: NCT03534453. Registered at May 23, 2018.

Tanshinone IIA inhibits endometrial carcinoma growth through the MAPK/ERK/TRIB3 pathway.

Endometrial carcinoma is the most common gynecological tumor in developed countries. Tanshinone IIA is a traditional herbal medicine which is to treat cardiovascular disease and has been shown to have various biological effects, such as anti-inflammatory, antioxidative and antitumor activities. However, there has been no study about the effect of tanshinone IIA on endometrial carcinoma. Thus, the aim of this study was to determine the antitumor activity of tanshinone IIA against endometrial carcinoma and investigate the associated molecular mechanism. We demonstrated that tanshinone IIA induced cell apoptosis and inhibited migration. We further demonstrated that tanshinone IIA activated the intrinsic (mitochondrial) apoptotic pathway. Mechanistically, tanshinone IIA induced apoptosis by upregulating TRIB3 expression and inhibiting the MAPK/ERK signaling pathway. In addition, knockdown of TRIB3 with an shRNA lentivirus accelerated proliferation and attenuated inhibition mediated by tanshinone IIA. Finally, we further demonstrated that tanshinone IIA inhibited tumor growth by inducing TRIB3 expression in vivo. In conclusion, these findings suggest that tanshinone IIA has a significant antitumor effect by inducing apoptosis and may be used as a drug for the treatment of endometrial carcinoma.

Aptamers dimerization inspired biomimetic clamp assay towards impedimetric SARS-CoV-2 antigen detection.

Antigen-detecting rapid diagnostic testing (Ag-RDT) has contributed to containing the spread of SARS-CoV-2 variants of concern (VOCs). In this study, we proposed a biomimetic clamp assay for impedimetric SARS-CoV-2 nucleocapsid protein (Np) detection. The DNA biomimetic clamp (DNA-BC) is formed by a pair of Np aptamers connected via a T20 spacer. The 5'- terminal of the DNA-BC is phosphate-modified and then anchored on the surface of the screen-printed gold electrode, which has been pre-coated with Au@UiO-66-NH2. The integrated DNA-material sensing biochip is fabricated through the strong Zr-O-P bonds to form a clamp-type impedimetric aptasensor. It is demonstrated that the aptasensor could achieve Np detection in one step within 11 min and shows pronounced sensitivity with a detection limit of 0.31 pg mL-1. Above all, the aptasensor displays great specificity and stability under physiological conditions as well as various water environments. It is a potentially promising strategy to exploit reliable Ag-RDT products to confront the ongoing epidemic.

The effect of albumin and hemoglobin levels on the prognosis of early-stage cervical cancer: a prospective, single-center-based cohort study.

BACKGROUND: Serum albumin (ALB) and hemoglobin (HGB) are important serum biochemical indices of the nutritional status of patients and are associated with cancer development. We investigated the relationship between ALB and HGB levels and clinicopathologic characteristics of early-stage cervical cancer to determine the influence of ALB and HGB on the prognosis of early-stage cervical cancer. METHODS: The clinical data of 560 patients with International Federation of Gynaecology and Obstetrics (FIGO, 2009) stage IA1-IIA2 cervical cancer from January 2005 to December 2010 were retrospectively analyzed. The relationship between serum ALB and HGB levels and clinicopathological characteristics of patients were analyzed. The patients were followed-up for 12-138 months. The effects of ALB and HGB levels on the prognosis were analyzed by Cox regression, log-rank test, and the Kaplan-Meier method. RESULTS: The rate of patients with pelvic lymph node metastasis (PLNM), tumor diameter ≥ 4 cm, lymphovascular space invasion (LVSI), and deep stromal invasion was significantly higher in the anemia and hypoalbuminemia group than in the normal group (P < 0.05). The progression-free survival (PFS) and overall survival (OS) of patients in the hypoalbuminemia group and anemia group were significantly lower than that of the normal group (P < 0.05). FIGO stage, tumor diameter, PLNM, depth of stromal invasion, LVSI, the levels of ALB and HGB were risk factors for the prognosis of cervical cancer patients (P < 0.05). CONCLUSION: Patients with hypoproteinemia and anemia in early-stage cervical cancer are more likely to have higher tumor stage, larger tumor size, PLNM, LVSI, and deep stromal invasion. In addition, patients with hypoproteinemia and anemia have a poorer prognosis than those without the condition. Therefore, it is of great significance to detect the ALB and HGB levels of patients and improve the nutritional status of patients in a timely manner for better prognosis of cervical cancer.

Neoadjuvant chemotherapy for patients with international federation of gynecology and obstetrics stages IB3 and IIA2 cervical cancer: a multicenter prospective trial.

BACKGROUND: Preoperative neoadjuvant chemotherapy (NACT) has been widely used in developing countries for the treatment of patients with International Federation of Gynecology and Obstetrics (FIGO) stages IB3 and IIA2 cervical cancer. However, the effectiveness of NACT and treatment options for NACT-insensitive patients have been concerning. This study will assess prognostic differences between NACT and primary surgery treatment (PST), determine factors associated with prognosis, and explore better adjuvant treatment modalities for NACT-insensitive patients. METHODS: This study analyzed clinical characteristics, pathological characteristics, treatment options, and follow-up information of 774 patients with FIGO stages IB3 and IIA2 cervical cancer from 28 centers from January 2016 to October 2019 who participated in a multicenter, prospective, randomized controlled trial. RESULTS: For patients undergoing NACT, the 5-year OS and PFS rate was 85.8 and 80.5% respectively. They were similar in the PST group. There was no significant difference in OS and PFS between clinical response (CR)/partial response (PR) groups and stable disease (SD)/progressive disease (PD) groups. Apart from deep cervical invasion (p = 0.046) affecting OS for patients undergoing NACT, no other clinical and pathological factors were associated with OS. 97.8% of NACT-insensitive patients opted for surgery. If these patients did not have intermediate- or high-risk factors, whether they had undergone postoperative adjuvant therapy was irrelevant to their prognosis, whereas for patients with intermediate- or high-risk factors, adjuvant chemotherapy resulted in better PFS (chemotherapy vs. no therapy, p < 0.001; chemotherapy vs. radiotherapy, p = 0.019) and OS (chemotherapy vs. no therapy, p < 0.001; chemotherapy vs. radiotherapy, p = 0.002). CONCLUSIONS: NACT could be a choice for patients with FIGO stages IB3 and IIA2 cervical cancer. The main risk factor influencing prognosis in the NACT group is deep cervical invasion. After systematic treatment, insensitivity to NACT does not indicate a poorer prognosis. For NACT-insensitive patients, Chinese prefer surgery. Postoperative adjuvant therapy in patients with no intermediate- or high-risk factors does not improve prognosis, and chemotherapy in patients with intermediate- and high-risk factors is more effective than radiation therapy and other treatments. TRIAL REGISTRATION: The study was prospectively registered on ClinicalTrials.gov (NCT03308591); date of registration: 12/10/2017.

Using Silva pattern system to predict prognosis and plan treatment of invasive endocervical adenocarcinoma: a single-center retrospective analysis.

BACKGROUND: This study evaluated the prognostic value of the Silva pattern system for invasive endocervical adenocarcinoma (EAC) by analysing its association with clinical and pathological features to provide more appropriate clinical management. METHODS: A retrospective analysis including 63 patients with pathological diagnosis of invasive EAC was performed from March 2011 to December 2016 at our hospital. All pathological slides were reviewed by three senior pathologists, and cases were stratified into patterns A, B, or C by consensus according to the Silva pattern system criteria. Clinicopathological characteristics and follow-up of the three Silva subgroups were analysed. RESULTS: Silva A, B, and C EAC patients were compared based on tumour size, clinical stage, lymphovascular invasion (LVI), and depth of invasion (DOI). The differences were found to be statistically significant (p < 0.01). There was no statistically significant difference in the proportion of lymph node metastasis among the three groups (p > 0.05) or in the recurrence and mortality rates of patients with Silva A, B, and C EAC (p > 0.05). Single factor analysis showed that tumour size, clinical stage, lymph node metastasis, LVI, and DOI were related to postoperative recurrence, whereas age, Silva classification, and postoperative recurrence were not correlated. CONCLUSION: The Silva classification system can predict lymph node status and prognosis of invasive EAC, but it cannot be used as an independent indicator. Individualized treatment plans should be adopted for patients with EAC.

Anlotinib Exerts Inhibitory Effects against Cisplatin-Resistant Ovarian Cancer In Vitro and In Vivo.

Background: Anlotinib is a highly potent multi-target tyrosine kinase inhibitor. Accumulating evidence suggests that anlotinib exhibits effective anti-tumor activity against various cancer subtypes. However, the effects of anlotinib against cisplatin-resistant (CIS) ovarian cancer (OC) are yet to be elucidated. The objective of this study was to investigate the inhibitory effect of anlotinib on the pathogenesis of cisplatin-resistant OC. Materials and Methods: Human OC cell lines (A2780 and A2780 CIS) were cultured and treated with or without anlotinib. The effects of anlotinib on cell proliferation were determined using cell-counting kit-8 and colony-formation assays. To evaluate the invasion and metastasis of OC cells, we performed wound-healing and transwell assays. The cell cycle was analyzed via flow cytometry. A xenograft mouse model was used to conduct in vivo studies to verify the effects of anlotinib. The expression of Ki-67 in the tumor tissue was detected via immunohistochemistry. Quantitative real-time polymerase chain reaction and Western blotting were used to measure the mRNA and protein levels. Results: Our study revealed that anlotinib significantly inhibited the proliferation, migration, and invasion of A2780 and A2780 CIS in a dose-dependent way in vitro (p < 0.05). Through R software 'limma' package analysis of GSE15372, it was found that, in comparison with A2780, PLK2 was expressed in significantly low levels in the corresponding cisplatin-resistant strains. The ERK1/2/Plk2 signaling axis mediates the inhibitory effect of anlotinib on the proliferation and migration of ovarian cancer cell lines. Moreover, our research found that anlotinib effectively inhibited the growth of tumor cells in an OC xenograft mouse model. Conclusions: In this study, anlotinib showed excellent inhibitory effects against cisplatin-resistant OC both in vitro and in vivo. These results add to the growing body of evidence supporting anlotinib as a potential anticancer agent against OC.

Necessity for subsequent surgery in women of child-bearing age with positive margins after conization.

BACKGROUND: 20-25% of women with high-grade cervical intraepithelial neoplasias (HSIL) have residual lesions after conization. The state of the margin is generally considered to be a risk factor for recurrence or persistent lesions. Predictors of positive margins and residual lesions need to be identified. A design for postoperative management and avoidance of overtreatment needs to be provided, especially for women of child-bearing age. METHODS: This study was a retrospective analysis of 1309 women of child-bearing age with HSIL, who underwent cold knife conization (CKC). Age, gravidity, parity, human papillomavirus (HPV) species, cytology, transformation zone type, results of endocervical curettage (ECC), quadrant involvement, glandular involvement, and Cervical Intraepithelial Neoplasia (CIN) grade were analyzed. Among those with positive margins, 245 patients underwent secondary surgery within three months, including CKC, a loop electrosurgical excision procedure, and total hysterectomy. Risk factors for positive margins and residual lesions were assessed. RESULTS: There was no significant difference in age, gravidity, parity, glandular involvement, and CIN grade between the two groups (P > 0.3). There was a significant difference in HPV species, cytology, ECC results, and quadrant involvement (P < 0.002). Multivariate analysis showed a major cytology abnormality, high-risk HPV infection, type III transformation zone, positive ECC result, and multiple quadrant involvement were independent risk factors for positive margins and residual lesions (P < 0.02). Age > 35 years was also a risk factor for residual lesions (P < 0.03). CONCLUSION: High-risk women should be treated appropriately considering fertility. Patients with positive margins should be managed uniquely. Surgery for women without fertility may be appropriate. Close follow-up is necessary for women who have fertility requirements or are unwilling to undergo subsequent surgery if they have no risk factors, especially women < 35 years.

Risk factors for the development of tubo-ovarian abscesses in women with ovarian endometriosis: a retrospective matched case-control study.

BACKGROUND: The purpose of this study was to assess the risk factors associated with the development of tubo-ovarian abscesses in women with ovarian endometriosis cysts. METHODS: This retrospective single-center study included 176 women: 44 with tubo-ovarian abscesses associated with ovarian endometriosis and 132 age-matched (1:3) patients with ovarian endometriosis but without tubo-ovarian abscesses. Diagnoses were made via surgical exploration and pathological examination. The potential risk factors of tubo-ovarian abscesses associated with ovarian endometriosis were evaluated using univariate analysis. The results (p ≤ 0.05) of these parameters were analyzed using a multivariate model. RESULTS: Five factors were included in the multivariate conditional logistic regression model, including in vitro fertilization, presence of an intrauterine device, lower genital tract infection, spontaneous rupture of ovarian endometriosis cysts, and diabetes mellitus. The presence of a lower genital tract infection (odds ratio 5.462, 95% CI 1.772-16.839) and spontaneous rupture of ovarian endometriosis cysts (odds ratio 2.572, 95% CI 1.071-6.174) were found to be statistically significant risk factors for tubo-ovarian abscesses associated with ovarian endometriosis. CONCLUSIONS: Among the factors investigated, genital tract infections and spontaneous rupture of ovarian endometriosis cysts were found to be involved in the occurrence of tubo-ovarian abscesses associated with ovarian endometriosis. Our findings indicate that tubo-ovarian abscesses associated with ovarian endometriosis may not be linked to in vitro fertilization as previously thought.

Clinical presentation, treatment, and outcomes associated with vaginal intraepithelial neoplasia: A retrospective study of 118 patients.

The incidence of vaginal intraepithelial neoplasia (VAIN) is increasing annually; however, the reported values are likely underestimated. Risk factors for VAIN include advanced age, human papillomavirus (HPV) infection, history of hysterectomy, and simultaneous or previous cervical intraepithelial neoplasia (CIN) or cervical cancer cervical cancer. The most common presentation is abnormal cytology without clinical symptoms. Despite various treatment modalities available, the rate of disease recurrence is high, and its malignant potential has been documented. This study aimed to examine demographic and clinical characteristics and associated treatment outcomes of patients with VAIN. We retrospectively reviewed clinicopathologic data and clinical outcomes of patients diagnosed with VAIN at a single center between January 2010 and December 2017. Overall, 118 patients were included (average age 49.81 ± 9.77 years; range, 26-70 years). The distribution of the histologic grade was as follows: VAIN1, 30.5%; VAIN2, 41.5%; and VAIN3, 28.0%. In total, 97 (82.2%) patients had either prior or simultaneous cervical lesions, CIN (35.6%), or cervical cancer (55, 46.6%). A total of 100 cases (84.7%) were diagnosed using colposcopy and 18 (15.3%) were diagnosed by pathological accident after hysterectomy. Thin-prep cytology test (TCT) results were available for 112 (94.9%) patients, and 111 (94.1%) patients had abnormal cytology findings. Most patients were confirmed as HPV positive (115, 97.5%), and 84 (71.2%) patients were confirmed as positive for high-risk HPV types. Forty-two (35.6%) patients underwent hysterectomy before VAIN diagnosis, and the median interval between hysterectomy and VAIN diagnosis was 26.5 (range: 3-68) months. Most surgical indications were HPV-related diseases (34, 80.9%), such as CIN (8, 19.0%) or cervical cancer (26, 61.9%). Eight patients had no history of cervical lesions. A total of 100 patients underwent initial treatment. During the median follow-up period of 29 (range: 9-96) months, 78 (78%) patients experienced disease remission after initial treatment, 7 (7%) experienced disease recurrence, 10 (10%) had persistent disease, and 5 (5%) had progressive disease. Finally, two patients developed vaginal cancer without death. Colposcopy should be performed before vaginal hysterectomy for VAIN, particularly HPV-related cases. The incidence of VAIN was 20% after hysterectomy owing to non-HPV-related lesions; thus, this part of the screening should not be discontinued. VAIN grade 2,3 and VAIN associated with CIN or cervical cancer are disease types more likely to recur and progress to invasive cancer; active medical intervention is recommended.

The effectiveness of cold-knife conization (CKC) for post-menopausal women with cervical high-grade squamous intraepithelial lesion: a retrospective study.

BACKGROUND: The effectiveness of surgery of high-grade squamous intraepithelial lesion in post-menopausal women needs to be investigated. This study evaluated the clinical significance of cold-knife conization in the diagnosis and surgery of cervical high-grade squamous intraepithelial lesions in post-menopausal women. METHODS: We conducted a retrospective analysis of post- and pre-menopausal patients with high-grade squamous intraepithelial lesion. All patients received cold-knife conization as the primary therapy. RESULTS: The satisfactory rate of colposcopy was significantly lower in the post-menopausal group than in the pre-menopausal group (38.33 vs. 71.25%; χ2 = 36.202, P < 0.001). The overall positive margin rate of cold-knife conization (25.83 vs 12.50%; χ2 = 10.106, P = 0.001) and rate of positive endocervical cone margins (16.67 vs. 4.58%; χ2 = 14.843, P < 0.001) were significantly higher in the post-menopausal group. Moreover, 49 post- and 60 pre-menopausal women underwent subsequent surgical treatment (40.83 vs. 25.00%). Residual rate of positive and negative margins in patients before and after menopause was significantly different (χ2 = 5.711, P = 0.017; χ2 = 12.726, P < 0.001, respectively). The recurrence rate in post-menopausal women remained 3.85%. CONCLUSIONS: Cold-knife conization can be performed as a primary procedure for diagnosis and surgery of post-menopausal patients with high-grade squamous intraepithelial lesions. Sufficient deep excisions are necessary to avoid positive endocervical margins, which can reduce the residual and recurrence of postoperative lesions.

Key factors mediated by PI3K signaling pathway and related genes in endometrial carcinoma.

By analyzing the gene expression of endometrial carcinoma (EC) patients, the key factors in PI3K signaling pathway and its related genes mediating EC were explored. The EC samples and normal endometrial samples were downloaded from TCGA database and GTEx database. The R language "limma" package was used for differential analysis, and the expression level of genes in each tissue was analyzed by "gganatogram" package. Functional enrichment analysis of differential genes was carried out by KOBAS, an online bioinformatics website. The correlation between key genes and differential genes was evaluated using TCGA data and GTEx combined gene expression data. The corresponding clinical data were downloaded from TCGA database and GTEx database, and the R language "survival" package was used to assess the potential of candidate differential genes as a key factor of EC. Based on the combined differential analysis of TCGA and GTEx databases, 299 genes with significant differential in expression were finally got. Functional enrichment analysis revealed that genes were predominantly enriched in the entry of "Pathways in cancer", including RAC2 and PIK3R3 genes which were related with the abnormal PI3K pathway in cancer. PIK3R3, a key gene in the PI3K signaling pathway, was highly-expressed in EC. SPDEF, GCNT2, KIAA1324, C9orf152, MARVELD3, and APEX2 genes were found to be positively correlated with PIK3R3 in EC, all of which were highly expressed in EC. KM survival analysis showed that SPDEF, GCNT2, KIAA1324 and C9orf152 were significantly correlated with patients' survival. ROC analysis showed that SPDEF, GCNT2, KIAA1324 and C9orf152 gene could be used as potential markers for prognosis and survival of EC patients. It was found that PIK3R3, a key gene in the PI3K signaling pathway, was highly expressed in EC. The SPDEF, GCNT2, KIAA1324 and C9orf152 genes were also highly expressed in EC, and were positively correlated with PIK3R3 in EC. Moreover, they are significantly correlated with the patients' survival, suggesting that they may be potential markers for the prognosis of patients with EC.

Association of hemorrhage at termination in caesarean scar pregnancy using the crossover sign of ultrasound image.

PURPOSE: To analyze whether crossover sign (COS) can help predict the risk of bleeding during surgical evacuation in patients with caesarean scar pregnancy (CSP). METHODS: This study retrospectively analyzed the clinical presentations, ultrasound images and treatment outcomes of patients with CSP. The relationship among the gestational sac, caesarean scar and the anterior uterine wall, defined as the COS, was analyzed to predict the risk of severe bleeding during surgical evacuation in these patients. All patients were categorized according to the relationship between the endometrial line and the superior-inferior diameter of the gestational sac into crossover sign-1 and crossover sign-2 groups. The Mann-Whitney U test was used to compare the data with non-normal distribution, and logistic regression analysis was performed to identify the correlates of severe bleeding. RESULTS: A total of 74 patients were included. In COS-1 group (n = 21), 16 (76.19%) patients suffered heavy bleeding(≥200 mL) during surgical evacuation, while COS-2 group (n = 53) had only 1(11.89%) patient complaint of heavy bleeding (≥200 mL) (P < 0.01). Adverse surgical outcomes were more common in women with COS-1. Logistic regression analysis showed that COS-1 (OR, 7.93; 95% CI, 1.35-46.67) was independently associated with severe bleeding. CONCLUSION: COS can help predict who has a higher risk of severe hemorrhage in patients with CSP and guide the clinical treatment selection for optimal management of this condition.

An Efficient Conservative Treatment Option for Cervical Pregnancy: Transcatheter Intra-Arterial Methotrexate Infusion Combined with Uterine Artery Embolization Followed by Curettage.

BACKGROUND The aim of this study was to assess the clinical outcomes of conservative treatments for cervical ectopic pregnancy (CEP). MATERIAL AND METHODS The series of CEP cases at our hospital between 2009 and 2016 were reviewed retrospectively. The patients were treated using systemic methotrexate infusion (MTX group, n=9), angiographic uterine artery embolization (UAE group, n=11), or transcatheter intra-artery methotrexate infusion combined with UAE (UAE+MTX group, n=13). Clinical outcomes, complications, and fertility were evaluated. RESULTS The median serum ß-hCG was 6449 mIU/mL for MTX group, 17384 mIU/mL for UAE group, and 21361 mIU/mL for UAE+MTX group. The difference was statistically significant. In the MTX group, 1 patient developed hepatotoxicity and 2 patients occurred continuous vaginal bleeding during curettage. These 3 patients were successfully treated with emergency UAE. In the UAE group, 2 patients had vaginal re-bleeding on postoperative day 17 and 26, respectively, and received a second UAE procedure. In the UAE+MTX group, no patients developed severe complications. Moreover, a quick regression of serum ß-hCG level, shortened recovery of normal menstruation, rapid cervical mass elimination, and a short hospital stay were observed in patients of the UAE+MTX group. CONCLUSIONS The triple therapy of transcatheter intra-arterial methotrexate infusion combined with UAE followed by immediate curettage is feasible and advantageous in treating CEP.

Antidiabetic Medications and the Risk of Endometrial Cancer in Patients.

BACKGROUND: Recent epidemiological studies suggest that antidiabetic medications (ADMs) may reduce the risks of cancer and cancer mortality among patients with type 2 diabetes. However, data on its effect on endometrial cancer (EC) are unclear. In this systematic review and meta-analysis, we evaluated the association between metformin, sulfonylureas (SUs), insulin, and the risk of EC in patients with diabetes mellitus (DM). METHODS: Studies were identified from PubMed and EMBASE database through October 2017. Observational studies reporting relative risks OR or provided data for their estimation were selected. Summary OR estimates with 95% CIs were estimated using the random-effects model. RESULTS: Six studies (2 retrospective cohorts and 4 case-control trials) reported 4,739 cases of EC in 510,344 patients with DM. Meta-analysis of observational studies showed no significant association between metformin (n = 6 studies; unadjusted OR 1.15; 95% CI 0.70-1.88; p = 0.59), SUs (unadjusted OR 1.11, 95% CI 0.94-1.32, p = 0.23), or insulin (n = 3 studies; unadjusted OR 1.15; 95% CI 0.93-1.40; p = 0.19) use and risk of developing EC. However, when we do heterogeneity and sensitivity analysis, the use of metformin was associated with an increased incidence of endometrial EC compared to no metformin use (unadjusted OR 1.29; 95% CI 1.16-1.44; p < 0.01). CONCLUSION: Our data indicate that metformin, SUs, and insulin did not meaningfully affect the risk of EC. Further investigation is warranted.

Factors associated with ovarian endometriosis malignancy and its recurrence in Chinese women.

In this study, the risk factors for ovarian endometriosis (OE) malignancy and its recurrence were explored in Chinese women. For OE malignancy occurrence, the age of marriage, abortion times, course of OE, body mass index (BMI), other benign uterine complications, and shorter parturition times were identified as risk factors using univariate analyses. Among them, age at marriage, course of OE, BMI, and decreased parturition times were identified as risk factors using multivariate analyses. For OE malignancy recurrence, the risk factors included clinical staging, histological classification, and chemotherapy by univariate analysis; and clinical stage, clear-cell carcinoma, and fewer chemotherapy cycles by multivariate analyses. In summary, we concluded that higher ages at marriage, longer courses of ovarian endometriosis, shorter parturition times, and additional benign uterine complications may increase the risk of OE malignancy. Advanced clinical stages, clear-cell carcinomas, and fewer chemotherapy cycles may promote OE malignancy recurrence. Impact statement What is already known on this subject? Endometriosis is one of the most common gynaecological diseases. Although endometriosis is not a malignant disease, endometriosis cells have characteristics similar to cancer cells. The risk of malignant transformation rates of ovarian endometriosis is said to be 1:18. However, epidemiological evidence based on large population research in ovarian endometriosis malignancy is lacking. In addition, there were few studies focussing on the long-term prognosis of ovarian endometriosis malignancies. What do the results of this study add? This study revealed the possible occurrence and recurrence risk factors of ovarian endometriosis malignancy using univariate and multivariate statistics analyses. What are the implications of these findings for clinical practice and/or further research? A clinical retrospective study with a longer follow-up period is suggested for assessing the occurrence and recurrence risk factors for ovarian endometriosis malignancies.

Clinical evaluation of human papillomavirus 16/18 oncoprotein test for cervical cancer screening and HPV positive women triage.

HPV-16 and -18 account for about 80% of cervical cancers. We evaluated the performance of HPV-16/18 oncoprotein to predict precancer and cancer in corresponding tissue biopsy specimens. 1,008 women attending cervical cancer screening program and 638 women referred to colposcopy with biopsy-confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+) from 4 hospitals were recruited (1,646 in total). All women were tested OncoE6 (AVC), Liquid-Based Cytology (Hologic) and cobas HPV test (Roche). Colposcopy was performed on women with any abnormal results. The final diagnoses were based on a consensus panel review of the histology. There were 919 normal, 69 CIN1, 53 CIN2, 91 CIN3,474 squamous cell carcinoma(SCC) and 40 adenocarcinoma (ADC) cases, the prevalence of OncoE6 was 1.7%, 10.1%, 13.2%, 44.0%, 80.4% and 65.0%, respectively. The percent positive for cobas was higher than that of OncoE6 in detection of HPV16/18 in entire population (p < 0.001). However, the disparity of positive rate between these two tests became tiny among cervical cancer patients (CIN2: 26.4% vs. 13.2%, CIN3: 73.6% vs. 44.0%, SCC: 84.0% vs. 80.4%, ADC: 67.5% vs. 65.0%). OncoE6 was less sensitive than cobas (73.9% vs. 93.6%, p < 0.001), but more specific (97.1% vs. 75.4%, p < 0.001) for CIN3+ in entire population; OncoE6 yielded a sensitivity of 77.7% and a specificity of 91.0% for CIN3+ among cobas positive women, which can reduce nearly half of the colposcopy referral numbers. OncoE6 can be considered as a useful tool for cervical cancer screening and a potential powerful biomarker for HPV positive triage.

Short-term Outcomes and Pregnancy Rate After Laparoscopic Fertility-Sparing Surgery for Borderline Ovarian Tumors: A Single-Institute Experience.

OBJECTIVE: We investigated the short-term outcomes and pregnancy rate after a laparoscopic approach to fertility preservation in patients with borderline ovarian tumors (BOTs). METHODS: Clinic-pathologic variants of patients with BOTs who underwent conservative surgery at the Tianjin Central Hospital of Obstetrics and Gynecology between January 2009 and July 2015 were retrospectively analyzed. RESULTS: Among 211 patients with BOTs, 74 (35.1%) received conservative surgery (44 cases using a laparoscopic approach and 30 cases using a laparotomy approach). The mean age of the laparotomy group was significantly younger than that of the laparoscopic group (P = 0.024). The maximal longitude of the tumor in the laparotomy group was significantly longer than that in the laparoscopic group (P < 0.001). The number of incomplete surgery cases in the laparoscopic group was significantly greater than that in the laparotomy group (P < 0.001). The 2 groups showed no significant differences in gravidity and parity before surgery, abnormality of serum tumor makers, tumor lateralities, ascites, histology, duration of follow-up, pregnancy rate after surgery, or postoperative recurrence. Total recurrent rate was 6.7% (5/74). Two cases in laparotomy group and 3 cases in laparoscopic group relapsed respectively. There was no significant difference of recurrent rate between the 2 groups. The total pregnant rate was 33.8% (25/74). Nine patients (30%) in the laparotomy group and 16 patients (36.4%) in the laparoscopic group became pregnant during follow-up respectively. There were no significant differences in the postoperative durations of pregnancy, pregnancy type, age at pregnancy, tumor lateralities, ascites, or type of pathology between 2 groups. The pregnancy rate of incomplete surgery cases in laparoscopic group was significantly higher than that of laparotomy group (P = 0.011). No recurrence occurred among the pregnant cases. CONCLUSIONS: A comprehensive laparoscopic surgery was not performed in incomplete surgery patients undergoing complete exploration. Good short-term outcomes and pregnancy were observed in patients receiving conservative laparoscopic surgery for BOTs, especially in patients receiving incomplete conservative laparoscopic surgery.

Perfusion and diffusion characteristics of endometrial malignancy based on intravoxel incoherent motion MRI at 3.0 T: comparison with normal endometrium.

BACKGROUND: There has been a growing need for a non-invasive imaging method for the accurate diagnosis and differentiation of endometrial malignancy (EM). PURPOSE: To study tissue characteristics of EM using an intravoxel incoherent motion (IVIM) model and to assess their diagnostic potential. MATERIAL AND METHODS: Sixty-eight EMs and 31 healthy participants were prospectively recruited for diffusion-weighted (13 b-values, b = 0-3,000 s/mm(2)) and standard magnetic resonance imaging (MRI). A bi-exponential analysis was performed to derive f (perfusion fraction), D* (pseudodiffusion coefficient), and D (true diffusion coefficient) in EM and normal endometrium (NE). Apparent diffusion coefficient (ADC) was calculated. Student's t test, the Mann-Whitney U test and a receiver operating characteristics (ROC) curve analysis were performed. RESULTS: EM had lower f (37.809 ± 12.158%) and was significantly different from NE (P < 0.001). However, the EMs had higher D (0.503 ± 0.155 × 10(-3) mm(2)/s) and D* (19.796 ± 20.029 × 10(-3) mm(2)/s) and were all significantly different from NE (P < 0.001). D was significantly lower than ADC in NE (P < 0.001) but not in EM (P > 0.05). f ≤ 48.5%, D > 0.432 × 10(-3) mm(2)/s, D* > 4.94 × 10(-3) mm(2)/s, and ADC ≤ 0.542 × 10(-3) mm(2)/s could diagnose EM (AUC 0.786-0.961). CONCLUSION: EM has distinctive IVIM perfusion and diffusion characteristics with promising potential for earlier non-invasive diagnosis.