Optimizing Screening for Colorectal Cancer: An Algorithm Combining Fecal Immunochemical Test, Blood-Based Cancer-Associated Proteins and Demographics to Reduce Colonoscopy Burden.

BACKGROUND: Fecal Immunochemical Test (FIT) is widely used in population-based screening for colorectal cancer (CRC). This had led to major challenges regarding colonoscopy capacity. Methods to maintain high sensitivity without compromising the colonoscopy capacity are needed. This study investigates an algorithm that combines FIT result, blood-based biomarkers associated with CRC, and individual demographics, to triage subjects sent for colonoscopy among a FIT positive (FIT+) screening population and thereby reduce the colonoscopy burden. MATERIALS AND METHODS: From the Danish National Colorectal Cancer Screening Program, 4048 FIT+ (≥100 ng/mL Hemoglobin) subjects were included and analyzed for a panel of 9 cancer-associated biomarkers using the ARCHITECT i2000. Two algorithms were developed: 1) a predefined algorithm based on clinically available biomarkers: FIT, age, CEA, hsCRP and Ferritin; and 2) an exploratory algorithm adding additional biomarkers: TIMP-1, Pepsinogen-2, HE4, CyFra21-1, Galectin-3, B2M and sex to the predefined algorithm. The diagnostic performances for discriminating subjects with or without CRC in the 2 models were benchmarked against the FIT alone using logistic regression modeling. RESULTS: The discrimination of CRC showed an area under the curve (AUC) of 73.7 (70.5-76.9) for the predefined model, 75.3 (72.1-78.4) for the exploratory model, and 68.9 (65.5-72.2) for FIT alone. Both models performed significantly better (P < .001) than the FIT model. The models were benchmarked vs. FIT at cutoffs of 100, 200, 300, 400, and 500 ng/mL Hemoglobin using corresponding numbers of true positives and false positives. All performance metrics were improved at all cutoffs. CONCLUSION: A screening algorithm including a combination of FIT result, blood-based biomarkers and demographics outperforms FIT in discriminating subjects with or without CRC in a screening population with FIT results above 100 ng/mL Hemoglobin.

Pelvic Pain and Quality of Life Before and After Laparoscopic Bowel Resection for Rectosigmoid Endometriosis: A Prospective, Observational Study.

BACKGROUND: Surgery for rectosigmoid endometriosis carries a substantial risk of short- and long-term complications, which has to be counterbalanced against the potential effect of the procedure. Prospective data are scarce in the field of deep infiltrating endometriosis surgery. OBJECTIVE: The study aimed to assess pelvic pain and quality of life before and after laparoscopic bowel resection for rectosigmoid endometriosis. DESIGN: The study involved prospectively collected data regarding pelvic pain and quality of life before and after surgery. SETTINGS: It was conducted at a tertiary endometriosis referral unit at Aarhus University Hospital. PATIENTS: A total of 175 women were included. INTERVENTION: Patients underwent laparoscopic bowel resection for endometriosis. MAIN OUTCOME MEASURES: Questionnaires for pain (Numerical Rating Scale) and quality of life (RAND Short Form-36) were answered before and 1 year after surgery. Data on analgesic and hormone treatment were collected. Preoperative and postoperative pelvic pain and quality-of-life scores were compared, and risk factors for improvement/worsening were identified. RESULTS: A total of 97.1% of the women completed the 1-year follow up. A significant decrease (p = 0.0001) was observed on all pelvic pain parameters. Most profound was the decrease in dyschezia. A significant improvement on all quality-of-life scores was observed (p = 0.0001). A surgical complication did not have a negative impact on outcome 1 year after surgery. The postoperative outcome was not related to the type of surgery. LIMITATIONS: This is an observational study without a control group. Risk factor data should be interpreted with caution, because the study was relatively underpowered for some of the rare outcomes. CONCLUSIONS: A significant and clinically relevant improvement in pelvic pain and quality of life 1 year after laparoscopic bowel resection for endometriosis was found. We strongly recommend surgery for rectosigmoid endometriosis that is unresponsive to conservative treatment. See Video Abstract at http://links.lww.com/DCR/A472.

Protocol Outlines for Parts 1 and 2 of the Prospective Endoscopy III Study for the Early Detection of Colorectal Cancer: Validation of a Concept Based on Blood Biomarkers.

BACKGROUND: Programs for population screening of colorectal cancer (CRC) have been implemented in several countries with fecal immunochemical testing (FIT) as the preferred platform. However, the major obstacle for a feces-based testing method is the limited compliance that reduces the clinical sensitivity for detection of participants with non-symptomatic CRC. Therefore, research approaches have been initiated to develop screening concepts based on biomarkers in blood. Preliminary results show that protein, genetic, epigenetic, and metabolomic components may be valuable in blood-based screening concepts, particularly when combinations of the various components appear to lead to significant improvements. OBJECTIVES: The protocol described in this paper focuses on the validation of concepts based on biomarkers in blood in a major population screened by FIT. METHODS: In Part 1, participants will be identified and included through the Danish CRC Screening Program comprising initial FIT and subsequent colonoscopy to those with a positive result. Blood samples will be collected from 8000 FIT-positive participants, who are offered subsequent colonoscopy. Findings and interventions at colonoscopy together with personal data including co-morbidity will be recorded. Blood samples and data will also be collected from 6000 arbitrarily chosen participants with negative FIT. In Part 2, blood samples and data will be collected from 30,000 FIT-negative participants three times within 4 years. The blood samples will be analyzed using various in-house and commercially available manual and automated analysis platforms. RESULTS: We anticipate Part 1 to terminate late August 2016 and Part 2 to terminate late September 2022. The results from Parts 1 and 2 will be presented within 12 to 18 months from termination. CONCLUSIONS: The purpose of this study is to improve the efficacy of identifying participants with neoplastic bowel lesions, to identify false negative participants, to identify participants at risk of interval neoplastic lesions, to improve the compliance in screening sessions, and to establish guidelines for out-patient follow-up of at-risk participants based on combinations of blood-based biomarkers.