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Background:Blood-borne biomarkers for early detection of colorectal cancer (CRC) could markedly increase screening uptake. The aim of this study was to evaluate serum carcinoembryonic antigen (CEA), CYFRA21-1 and CA125 for the early detection of CRC in an asymptomatic cohort.Methods:This nested case-control study within UKCTOCS used 381 serial serum samples from 40 women subsequently diagnosed with CRC, 20 women subsequently diagnosed with benign disease and 40 matched non-cancer controls with three to four samples per subject taken annually up to 4 years before diagnosis. CEA, CYFRA21-1 and CA125 were measured using validated assays and performance of markers evaluated for different pre-diagnosis time groups.Results:CEA levels increased towards diagnosis in a third of all cases (half of late-stage cases), whereas longitudinal profiles were static in both benign and non-cancer controls. At a threshold of >5 ng ml−1 the sensitivities for detecting CRC up to 1 and 4 years before clinical presentation were 25% and 13%, respectively, at 95% specificity. At a threshold of >2.5 ng ml−1, sensitivities were 57.5% and 38.4%, respectively, with specificities of 81% and 83.5%. CYFRA21-1 and CA125 had no utility as screening markers and did not enhance CEA performance when used in combination. CEA gave average lead times of 17-24 months for test-positive cases.Conclusions:CEA is elevated in a significant proportion of individuals with preclinical CRC, but would not be useful alone as a screening tool. This work sets a baseline from which to develop panels of biomarkers which combine CEA for improved early detection of CRC. [ABSTRACT FROM AUTHOR]

Purpose: The preoperative diagnosis of endometriosis associated ovarian cancer (EAOC) remains challenging for lack of effective diagnostic biomarker. We aimed to study clinical characteristics and develop a nomogram for diagnosing EAOC before surgery. Methods: A total of 87 patients with EAOC and 348 patients with ovarian endometrioma (OEM) were enrolled in our study. Least absolute shrinkage and selection operator (LASSO) regression and Logistic regression were utilized to select variables and construct the prediction model. The performance of the model was assessed using receiver operating characteristic (ROC) analyses and calibration plots, while decision curve analyses (DCAs) were conducted to assess clinical value. Bootstrap resampling was used to evaluated the stability of the model in the derivation set. Results: The EAOC patients were older compared to the OEM patients (46.41 ± 9.62 vs. 36.49 ± 8.09 year, P < 0.001) and proportion of postmenopausal women was higher in EAOC group than in the OEM group (34.5 vs. 1.5%, P < 0.001). Our prediction model, which included age at diagnosis, tumor size, cancer antigen (CA) 19–9 and risk of ovarian malignancy algorithm (ROMA), demonstrated an area under the curve (AUC) of 0.858 (95% confidence interval (CI): 0.795–0.920) in the derivation set (N = 304) and an AUC of 0.870 (95% CI: 0.779–0.961) in the validation set (N = 131). The model fitted both the derivation (Hosmer–Lemeshow test (HL) chi-square = 12.600, P = 0.247) and the validation (HL chi-square = 8.210, P = 0.608) sets well. Conclusion: Compared to patients with OEM, those with EAOC exhibited distinct clinical characteristics. Our four-variable prediction model demonstrated excellent performance in both the derivation and validation sets, suggesting its potential to assist with preoperative diagnosis of EAOC. [ABSTRACT FROM AUTHOR]

To construct a nomogram for overall survival (OS) in colorectal cancer. Using Cox univariate and multivariate analysis, significant variables were plotted into a nomogram. The predictive accuracy and discriminative ability of the nomogram was determined using the concordance index (C-index), receiver operator characteristic curve and calibration curve. CA125 and tumor node metastasis (TNM) were identified as independent predictors for OS in colorectal cancer patients. Area under the curve (AUC) for 1, 3, and 5 years was 0.89, 0.723, and 0.71 respectively in primary cohort, and C-index was 0.702 (95% CI, 0.610 to 0.794) in validation cohort, which indicated a middle degree of accuracy. High-quality calibration plots were seen in the OS nomogram models. Age, CA125, and TNM were identified as poor predictors of colorectal cancer. This nomogram is a valuable predictive tool for the prognosis of colorectal cancer. [ABSTRACT FROM AUTHOR]

Recent studies in social endocrinology have explored the effects of social relationships on female reproductive steroid hormones—estradiol and progesterone—investigating whether they are suppressed in partnered and parous women. Results have been mixed for these hormones although evidence is more consistent that partnered women and women with young children have lower levels of testosterone. These studies were sequential to earlier research on men, based on Wingfield's Challenge Hypothesis, which showed that men in committed relationships, or with young children, have lower levels of testosterone than unpartnered men or men with older or no children. The study described here explored associations between estradiol and progesterone with partnership and parity among women from two different ethnicities: South Asian and white British. We hypothesized that both steroid hormones would be lower among partnered and/or parous women with children ≤3 years old, regardless of ethnicity. In this study we analyzed data from 320 Bangladeshi and British women of European origin aged 18 to 50 who participated in two previous studies of reproductive ecology and health. Levels of estradiol and progesterone were assayed using saliva and/or serum samples and the body mass index calculated from anthropometric data. Questionnaires provided other covariates. Multiple linear regressions were used to analyze the data. The hypotheses were not supported. We argue here that, unlike links between testosterone and male social relationships, theoretical foundations for such relationships with female reproductive steroid hormones are lacking, especially given the primary role of these steroids in regulating female reproductive function. Further longitudinal studies are needed to explore the bases of independent relationships between social factors and female reproductive steroid hormones. [ABSTRACT FROM AUTHOR]

Background: Screening programmes decrease the incidence of colorectal, breast and cervical cancer. As such, it is imperative that medical health professionals are educated on the screening programmes available and are aware of the research basis justifying them. Aims: To establish the attitudes of final-year medical students to a gynaecological cancer screening teaching session, provided as part of their core Obstetrics and Gynaecology module. Methods: A 3-h workshop, aimed to critically appraise research papers, reviewed cervical and ovarian cancer screening methods. The workshop was facilitated by a Consultant in Gynae-oncology Surgery. Anonymous evaluation was requested from two hundred nine students attending during the 2018/2019 academic year. Qualitative research with thematic analysis of content was performed. Results: One hundred fifty-six students gave evaluation on the workshop itself (74.6%). Three main themes were identified—support for the importance of teaching screening methods, appreciation of the importance of understanding cervical screening and a wish for further teaching in Critical Appraisal. Students identified that there was a need to understand screening, that it was "..important for us to consider the value of screening programmes". The teaching on Cervical screening was "..helpful, especially with cervical screening". Conclusions: Medical students expressed a wish to understand the research basis of a common clinical screening programme (for cervical cancer) as well as the research basis for not providing screening to low risk populations (for ovarian cancer). Further research in this area may include exploring how this is taught in other medical schools. [ABSTRACT FROM AUTHOR]

Management of pancreatic head (ductal adenocarcinoma) and periampullary cancer is difficult owing to its insidious onset and hence late diagnosis, lack of significant diagnostic, predictive and prognostic biomarkers, and the inherent tumor biology of being relatively resistant to chemotherapy and radiotherapy. Surgery of this deep-seated gland is technically challenging and the procedure is called pancreaticoduodenectomy (PD). It involves removal of pancreatic head, duodenum, bile duct and gallbladder ± distal stomach. The reconstruction involves pancreatoenteric anastomosis (pancreaticojejunostomy or pancreaticogastrostomy), hepaticojejunostomy, and gastro/duodenojejunostomy. At times, vascular resection and adjacent organ resection are required for complete extirpation (R0) of the cancer. Over the years, surgical procedures used in the management of pancreatic cancer (PC) have been refined and with better anesthesia and perioperative and postoperative care, the operative mortality has dropped to < 5% but morbidity still remains close to 40%. The most common cause of severe morbidity is occurrence of postoperative pancreatic fistula. Post pancreatectomy hemorrhage and delayed gastric emptying are the other two major morbidities extending hospital stay and are at times life-threatening. New classification systems, better imaging, and new chemotherapeutic/targeted drug combinations for neoadjuvant/adjuvant treatment with/without refined radiotherapy techniques and centralization of treatment have helped in selecting the best patients for aggressive treatment with the aim of improving abysmally low overall survival. The present review highlights recent updates in the management of PC. [ABSTRACT FROM AUTHOR]

More than one-fifth of ovarian cancers are hereditary, with most of them caused by BRCA genes. Malignant ovarian neoplasms are primarily epithelial tumors, a heterogeneous group of tumors with variable genetic backgrounds that translate into different biologic behaviors and morphologic features. Radiologists play an increasingly important role in the diagnosis and management of oncology patients. Familiarity with hereditary ovarian cancers will have a positive impact on patient management and radiologists' involvement in the multidisciplinary approach needed for this delicate patient population. In this paper, we review the basic histologic and genetic backgrounds of ovarian tumors with an emphasis on hereditary ovarian cancers, as well as the effects that these factors have on patient workup, primarily with regard to imaging studies. [ABSTRACT FROM AUTHOR]

Ovarian cancer is the leading cause of death among gynecologic malignancies. Combining cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) can benefit patients with advanced ovarian cancer. We evaluate the role of small bowel peritoneal cancer index (sb-PCI) score as a prognostic factor. We retrospectively analyzed characteristics and clinical outcomes of patients that underwent intermediate cytoreductive surgery combined with HIPEC after neoadjuvant chemotherapy and patient's characteristics underwent debulking surgery plus HIPEC for recurrence disease. One hundred thirty patients were included. Eighty-five of them (65.4%) were treated for recurrent ovarian cancer, while 45 (34.6%) underwent intermediate cytoreductive surgery after neoadjuvant chemotherapy with a mean age of 52 years. Mean intraoperative peritoneal cancer index (PCI) was 11.84 with a mean sb-PCI score of 5.57. Univariate analysis revealed that PCI, sb-PCI, and completeness of cytoreduction (CC) were parameters that correlated significantly with overall survival, while after multivariate analysis sb-PCI and CC were identified as independent prognostic factors of survival. A statistically significant correlation between sb-PCI score and overall survival of patients with advanced ovarian cancer was revealed. Further larger future studies are required to confirm our conclusion in order to change the treatment of advanced ovarian cancer patients. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is associated with one of the highest rates of mortality among cancers worldwide. The early detection and management of CRC is imperative. Biomarkers play an important role in CRC screening tests, CRC treatment, and prognosis and clinical management; thus rapid and sensitive detection of biomarkers is helpful for early detection of CRC. In recent years, electrochemical biosensors for detecting CRC biomarkers have been widely investigated. In this review, different electrochemical detection methods for CRC biomarkers including immunosensors, aptasensors, and genosensors are summarized. Further, representative examples are provided that demonstrate the advantages of electrochemical sensors modified by various nanomaterials. Finally, the limitations and prospects of biomarkers and electrochemical sensors in detection are also discussed. [ABSTRACT FROM AUTHOR]

Ovarian cancer diagnosis and the monitoring of ovarian cancer patients currently rely on the detection of the glycoprotein CA125 through a double-determinant immunoassay. This immunoassay may not provide accurate reporting of CA125 amounts in serum samples if the antibodies fail to detect all proteoforms (false negative results) or because of antibody binding to off-target proteins (false positive results). An immunoaffinity-free detection method, such as mass spectrometry–based bottom-up proteomics, would be an attractive alternative, but glycoproteins such as CA125 are notably challenging to analyze by such methods. Here, we demonstrate a proteomics workflow involving suspension trapping (STrap) sample preparation and deoxycholic acid as a passivating agent to reduce protein loss through adsorption; this approach enables improved protein coverage over conventional workflows (from 3 to 12% coverage of ascites-derived CA125). We expect that this rapid and simple sample preparation strategy will assist in the development of mass spectrometry-based assays for CA125 and other large glycoproteins. [ABSTRACT FROM AUTHOR]

An electrochemical immunoassay for the carcinoembryonic antigen is described. It is based on the use of Au NPs modified zeolitic imidazolate framework (ZIF-8) and ordered mesoporous carbon (OMC). Au NPs@ZIF-8 was synthesized by reduction of chloroauric acid. It serves as immobilization support nanocarrier to increase antibody loading due to its large surface area. OMC was dropped on a glassy carbon electrode to improve electrochemical signals due to enhanced electrical conductivity. Differential pulse voltammetry was carried out to record electrochemical responses (best measured at 0.26 V vs. Ag/AgCl). The immunosensor demonstrated excellent electrochemical performance with a linear determination range of 5 pg mL−1 to 400 ng mL−1 and a determination limit of 1.3 pg mL−1 (S/N = 3). The sensor also exhibited high selectivity, good stability, and acceptable reproducibility. [ABSTRACT FROM AUTHOR]

Outstanding research in the last few decades led to newer insights into the management of gynecological cancers. In the preventive arena, the efficacy and safety of HPV vaccination are well accepted and is now in addition to bi- and quadrivalent vaccines; there is a nonavalent vaccine against nine oncogenic HPV strains. Recent studies also looked into the dosaging schedules and age of vaccination against HPV to improve the vaccine efficacy and coverage. HPV testing is now approved as a primary screening test for cervical cancer in women aged more than 30 years with better sensitivity than the traditional cytology. Opportunistic salpingectomy for ovarian cancer prevention and neoadjuvant chemotherapy for advanced ovarian cancers are accepted practices. The role of personalized medicine in ovarian cancer and comprehensive genomic analysis of endometrial cancers are also covered in this review. [ABSTRACT FROM AUTHOR]

Background: High-grade serous carcinoma (HGSC) is the most common tubo-ovarian cancer. The fallopian tube harbours the precursor lesion: serous tubal intraepithelial carcinoma (STIC). Bilateral salpingo-oophorectomy is an effective risk-reducing surgical (RRS) strategy for breast cancer susceptibility gene mutation carriers (BRCAm). The value of RRS in those without defined genetic risk is unknown but these women represent a substantial cohort in prophylactic surgical practice.Methods: This is a retrospective review of RRS at an Irish university teaching hospital.Results: One hundred and thirty women underwent RRS; group 1 = 46 BRCAm; group 2 = 19 BRCAm negative/65 genetic status unknown. Group 1 had one occult HGSC. Group 2 had no STIC or cancers and were older and more likely to have hysterectomy and benign pathology. Other pathologies included serous tubal intraepithelial lesions (STIL) (2), p53 signatures (2), endometriosis (6), fibroids/adenomyosis (4) and atypical endometrial hyperplasia (1).Conclusion: More than 60% of women undergoing RRS were BRCAm negative or untested. Counselling of high-risk women without defined germline mutations remains a challenge for gynaecologists because the likelihood of removing STIC lesions or occult invasive cancer is low. Removal of coincidental pathology may give added value to RRS in these women. [ABSTRACT FROM AUTHOR]

Purpose: Mechanistic and observational data together support a role for prolactin in breast cancer development. Determinants of prolactin in Asian populations have not been meaningfully explored, despite the lower risk of breast cancer in Asian populations.Methods: Determinants of plasma prolactin were evaluated in 442 postmenopausal women enrolled in the Singapore Chinese Health Study, a population-based prospective cohort study. At baseline all cohort members completed an in-person interview that elicited information on diet, menstrual and reproductive history, and lifestyle factors. One year after cohort initiation we began collecting blood samples. Quantified were plasma concentrations of prolactin, estrone, estradiol, testosterone, androstenedione, and sex hormone-binding globulin (SHBG). Analysis of covariance method was used for statistical analyses with age at blood draw, time since last meal, and time at blood draw as covariates.Results: Mean prolactin levels were 25.1% lower with older age at menarche (p value = 0.001), and 27.6% higher with greater years between menarche and menopause (p value = 0.009). Prolactin levels were also positively associated with increased sleep duration (p value = 0.005). The independent determinants of prolactin were years from menarche to menopause, hours of sleep, and the plasma hormones estrone and SHBG (all p values < 0.01).Conclusion: The role of prolactin in breast cancer development may involve reproductive and lifestyle factors, such as a longer duration of menstrual cycling and sleep patterns. [ABSTRACT FROM AUTHOR]

Purpose of Review: Both conventional and novel approaches to early detection of ovarian cancer are reviewed in the context of new developments in our understanding of ovarian cancer biology. Recent Findings: While CA125 as a single value lacks adequate specificity or sensitivity for screening, large studies have shown that a 2-stage strategy which tracks CA125 change over time and prompts transvaginal ultrasound (TVS) for a small subset of women with abnormally rising biomarker values achieves adequate specificity and detects a higher fraction of early-stage disease. Sensitivity could clearly be improved in both blood tests and in imaging. Metastasis can occur from ovarian cancers too small to increase blood levels of protein antigens and a significant fraction of ovarian cancers arise from the fimbriae of fallopian tubes that cannot be imaged with TVS. Autoantibodies, miRNA, ctDNA, DNA methylation in blood, and cervical mucus might improve sensitivity of the initial phase and magnetic relaxometry and autofluorescence could improve imaging in the second phase. Summary: Enhancing the sensitivity of two-stage strategies for early detection could reduce mortality from ovarian cancer. [ABSTRACT FROM AUTHOR]