Excess Weight, Polygenic Risk Score, and Findings of Colorectal Neoplasms at Screening Colonoscopy.

INTRODUCTION: Excess weight is an established risk factor of colorectal cancer (CRC). However, evidence is lacking on how its impact varies by polygenic risk at different stages of colorectal carcinogenesis. METHODS: We assessed the individual and joint associations of body mass index (BMI) and polygenic risk scores (PRSs) with findings of colorectal neoplasms among 4,784 participants of screening colonoscopy. Adjusted odds ratios (aORs) for excess weight derived by multiple logistic regression were converted to genetic risk equivalents (GREs) to quantify the impact of excess weight compared with genetic predisposition. RESULTS: Overweight and obesity (BMI 25-<30 and ≥30 kg/m 2 ) were associated with increased risk of any colorectal neoplasm (aOR [95% confidence interval, CI] 1.26 [1.09-1.45] and 1.47 [1.24-1.75]). Obesity was associated with increased risk of advanced colorectal neoplasm (aOR [95% CI] 1.46 [1.16-1.84]). Dose-response relationships were seen for the PRS (stronger for advanced neoplasms than any neoplasms), with no interaction with BMI, suggesting multiplicative effects of both factors. Obese participants with a PRS in the highest tertile had a 2.3-fold (95% CI 1.7-3.1) and 2.9-fold (95% CI 1.9-4.3) increased risk of any colorectal neoplasm and advanced colorectal neoplasm, respectively. The aOR of obesity translated into a GRE of 38, meaning that its impact was estimated to be equivalent to the risk caused by 38 percentiles higher PRS for colorectal neoplasm. DISCUSSION: Excess weight and polygenic risk are associated with increased risk of colorectal neoplasms in a multiplicative manner. Maintaining normal weight is estimated to have an equivalent effect as having 38 percentiles lower PRS.

Effect of early inflammatory reaction on ovarian reserve after laparoscopic cystectomy for ovarian endometriomas.

This study aimed to investigate the effect of early inflammatory reaction on ovarian reserve of patients with ovarian endometriomas after laparoscopic cystectomy. Our retrospective case series included 112 patients with ovarian endometriomas that underwent the laparoendoscopic single-site cystectomy. Interleukin-6 (IL-6), hs-CRP, tumour necrosis factor-α (TNF-α), interleukin-17A (IL-17A) and AMH level were detected during perioperative and postoperative period. In our study, ovarian endometriomas with low AMH group were found having higher level of IL-6 than the normal AMH group in the preoperative status. On the 3rd day after operation, the change of AMH level was inversely proportional to the IL-6 level. During the follow-up within one year, it was found that the bilateral nature of the cyst and the postoperative IL-6 increased level were the risk factors for AMH not returning to baseline level. Our results suggested that inflammatory reaction is indeed involved in the damage of ovarian reserve during laparoscopic cystectomy. Hence, the negative impact of inflammatory injury should be fully considered before operation, especially young women with bilateral ovarian endometriomas.Impact StatementWhat is already known on this subject? Ovarian reserve in women always was reduced after the laparoscopic cystectomy. It is reported that it may be related to the use of energy instruments, haemostatic methods or the size of cysts in minimally invasive surgery.What do the results of this study add? Inflammatory reaction is indeed involved in the damage of ovarian reserve during LESS cystectomy. Interleukin-6 (IL-6) may act as the most main inflammatory factor aggravating damage of the ovarian reserve. Moreover, increased IL-6 level after surgery and bilateral cyst burden are the two risk factors for AMH not returning to baseline level within one year after surgery.What are the implications of these findings for clinical practice and/or further research? In clinic, the negative impact of inflammatory injury on ovarian reserve should be fully considered before operation, especially young women with bilateral ovarian endometriomas. Moreover, this is also the clinical basis for further study on the mechanism of inflammatory ovarian injury or the method of blocking the inflammatory response to reduce the damage of ovarian reserve after surgery.

CYR61, a potential biomarker of tumor inflammatory response in epithelial ovarian cancer microenvironment of tumor progress.

BACKGROUND: Recent studies have found that inflammatory response is involved in the pathogenesis of ovarian cancer. Advanced ovarian cancer is often presented with ascites that is rich in cytokines, inflammatory factors or cancer cells. Therefore, it is important to study the microenvironment of ascites in order to further clarify the occurrence and progression of ovarian cancer. As a pro-inflammatory factor, the Cyr61 expression patterns are inconsistent in human tumors. Although it has been reported that Cyr61 is related to the progression of ovarian cancer, its specific mechanism is not yet clear. This study sought to evaluate the Cyr61 levels of ascites, serum and different tissues of ovarian cancer to explore the potential association of Cyr61with the tumor-associated inflammatory microenvironment of EOC. METHODS: Tumor specimens were procured from patients with ovarian serous cystadenocarcinoma and ovarian serous cystadenoma. Cyr61 and IL-6 levels of serum or ascites were determined by ELISA (Enzyme-Linked ImmunoSorbent Assay), while Cyr61 expressions of different ovarian tumor tissues were evaluated by IHC (Immunohistochemistry). Then the correlation of Cyr61 level in ascites with clinicopathologic features was analyzed. And other laboratory data were obtained from medical records. RESULTS: Both in ascites and serum, significantly higher Cyr61 levels were found in ovarian serous cystadenocarcinoma. In malignant ascites, higher Cyr61 level of ovarian serous cystadenocarcinoma was more closely associated with FIGO stage, initial tumor size > 10 cm and the residual tumor size. And the increased IL-6 level was linearly related to Cyr61 level. Moreover, the serum levels of Cyr61, IL-6 and CRP in advanced stage of ovarian cancer were much higher than those in early stage. Lastly, the IHC data demonstrate that Cyr61 expression of ovarian serous adenocarcinoma was higher than that of ovarian serous cystadenoma, but it was lower than the paired metastatic lesions. CONCLUSIONS: As a pro-inflammatory factor, increased ascites Cyr61 level is associated with FIGO stage, initial tumor size > 10 cm and the residual tumor size. Moreover, serum Cyr61 may be used as a potential marker for EOC inflammatory response. Finally, Cyr61 may be involved in the process of tumor metastasis and progression by producing IL-6 and CRP in the EOC inflammatory microenvironment.

Application value of Caprini risk assessment model and elevated tumor-specific D-dimer level in predicting postoperative venous thromboembolism for patients undergoing surgery of gynecologic malignancies.

AIM: Venous thromboembolism (VTE) is a major cause of morbidity and mortality in gynecologic malignant patients after surgery. We aimed to validate the Caprini risk assessment model (RAM) and elevated tumor-specific D-dimer as predictive marker of postoperative VTE for patients undergoing surgery of gynecologic malignancies. METHODS: Inpatients were divided into five groups (low: score = 0-1; moderate: score = 2; high: score = 3-4; higher: score = 5-7; sup-high: score > 7) and treated according to their risk level after the surgery during the hospitalization according to the Caprini RAM. D-dimer level was detected during the perioperative period. If D-dimer did not fall to normal reference range on the seventh day after operation, the use of low-molecular-weight heparin was prolonged to 28 days after surgery. RESULTS: The majority (853/974, 87.6%) of the patients was in the Caprini score ≥5, with an overall VTE incidence of 1.75%. The VTE group had significantly higher Caprini score, CA125, vascular invasion rate and lymph node metastasis rate. If 1.5 µg/mL was used as the D-dimer cut-off value to predicting VTE, the sensitivity was 87.5%, the specificity was 93.8% and the negative predictive value was 99.2%. The D-dimer level was a marker for prolonging the anticoagulants use during the perioperative period, especially for the sup-high group. CONCLUSION: The Caprini RAM is an effective and reliable VTE risk prediction tool for patients undergoing gynecological malignant tumor surgery. The group (score ≥ 5) can be divided into two subgroups (higher: score = 5-7 and sup-high: score > 7), which may better predict the occurrence of VTE for malignant tumor patients. Great than 1.5 µg/mL D-dimer before operation should be given more attention for the presence of VTE.

Red and Processed Meat Intake, Polygenic Risk and the Prevalence of Colorectal Neoplasms: Results from a Screening Colonoscopy Population.

High red and processed meat intake and genetic predisposition are risk factors of colorectal cancer (CRC). However, evidence of their independent and joint associations on the risk of colorectal neoplasms is limited. We assessed these associations among 4774 men and women undergoing screening colonoscopy. Polygenic risk scores (PRSs) were calculated based on 140 loci related to CRC. We used multiple logistic regression models to evaluate the associations of red and processed meat intake and PRS with the risk of colorectal neoplasms. Adjusted odds ratios (aORs) were translated to genetic risk equivalents (GREs) to compare the strength of the associations with colorectal neoplasm risk of both factors. Compared to ≤1 time/week, processed meat intake >1 time/week was associated with a significantly increased risk of colorectal neoplasm [aOR (95% CI): 1.28 (1.12-1.46)]. This risk increase was equivalent to the risk increase associated with a 19 percentile higher PRS. The association of red meat intake with colorectal neoplasm was weaker and did not reach statistical significance. High processed meat intake and PRS contribute to colorectal neoplasm risk independently. Limiting processed meat intake may offset a substantial proportion of the genetically increased risk of colorectal neoplasms.

Prognostic analysis of antibody typing and treatment for antiphospholipid syndrome-related recurrent spontaneous abortion.

OBJECTIVE: To determine the efficacy of antibody typing and treatment on live birth rate in Chinese patients with antiphospholipid syndrome (APS)-related recurrent spontaneous abortion (RSA). METHODS: A retrospective study analyzed 4542 Chinese patients who experienced spontaneous abortion, of whom 314 had APS (272 primary and 42 secondary). Type of antibodies was tested. Anticoagulant and anti-inflammatory treatments were adopted according to the titer and type of antibodies. The incidence of repeated abortion and placental dysfunction, gestational age, and mean weight of the fetuses were recorded. RESULTS: Among the patients with APS-related RSA, primary APS accounted for the largest proportion. The proportion of antibody classification was as follows: ß2-glycoprotein 1 (ß2GP1)-IgM (151, 48.08%), lupus anticoagulant (LAC) (36, 11.46%), anticardiolipin (aCL)-IgM (32, 10.19%), ß2GP1-IgM and aCL-IgM (29, 9.23%), and aCL-IgG (16, 5.09%). After treatment, the negative conversion of antibody, including ß2GP1-IgM and LAC, significantly improved pregnancy outcomes. There was no significant difference in pregnancy outcomes between the other antibody titers. CONCLUSION: The combination of anticoagulant and anti-inflammatory treatment led to a higher live birth rate in the treatment of APS-related RSA, highlighting the potential of antibody typing in providing clinical guidance for the treatment of APS-related RSA.