EP.TU.296A Significant Difference in Cancer Proportions Between Two Modelled Cohorts Investigated by 2-WeekWait (2WW) Colorectal referral pathway

Aim To compare the proportions of malignancy between two modelled cohorts of referred and investigated by our colorectal 2 WW referrals pathway. Methods Two modelled cohorts were analysed from our prospectively maintained colorectal 2WW referrals database from August 2018 to July 2019. One cohort (group A) included patients without anemia, rectal mass or overt rectal bleeding. The other (group B) included the rest of referrals. Data collected and analysed in each group included total numbers of referrals, investigated referrals and malignancy proportion in each group. One tailed Z test was used to analysis statistical difference. Results 4240 referrals were made to our colorectal 2 WW pathway during the given period. 1333 (31%) were group A and 2907 (69%) were group B. Total number of patients investigated in group A was 1227, of those only 34 (2.8%) were colorectal cancer and 18 (1.5%) were extracolonic cancer. One the other hand, 2705 patients were investigated in group B, colorectal malignancy were found in 142 (5.3%) patients and 33 (1.2%) were extracolonic. There was a significant difference (p < 0.05) in total number of malignancies between Group A (53/4.3%) and Group B (175/6.5%). Conclusion While the 2 Week-Wait referral pathway plays an important role in rapid testing and identifying colorectal cancer, there was a difference between malignancy distribution within the referrals. this difference doesn’t reflect a clinical significance but it can be a good stratification tool.

Extracolonic Cancer Risk After Total Colectomy for Inflammatory Bowel Disease: A Population-based Cohort Study

Background Patients with inflammatory bowel disease are at increased risk of extracolonic cancers. Little is known regarding this risk following total colectomy [TC]. Methods Patients who underwent TC for inflammatory bowel disease in Denmark during 1977–2013 were identified from the Danish National Patient Registry. Incidence rates of extracolonic cancers were determined through record linkage to the Danish Cancer Registry and compared with expected incidence rates in the general population. Standardized incidence ratios [SIRs] were calculated as the observed vs expected cancer incidence. Results In total, 4430 patients (3441 with ulcerative colitis [UC]; 989 with Crohn’s disease [CD]) were followed for 54,183 person-years after TC. Following their surgery, 372 patients were diagnosed with extracolonic cancer compared to 331 expected [SIR = 1.1 (95% confidence interval {CI}: 1.0–1.2)]. The risk of extracolonic cancer overall was increased among patients with CD and TC (SIR = 1.5 [95% CI: 1.2–1.8]), but not among patients with UC and TC (SIR = 1.0 [95% CI: 0.9–1.2]). Patients with UC and TC had a higher risk of intestinal extracolonic cancer (SIR = 2.0 [95% CI: 1.4–2.7]). Patients with CD and TC had a higher risk of smoking-related cancers (SIR = 1.9 [95% CI: 1.2–2.9]), intestinal extracolonic cancer (SIR = 3.1 [95% CI: 1.6–5.5]) and immune-mediated cancers (SIR = 1.5 [95% CI: 1.0–2.1]). Conclusion Patients with CD and TC had a higher risk of extracolonic cancer overall compared to the general population, while patients with UC and TC did not. Site-specific cancer risk varied according to inflammatory bowel disease type.

Clean Colorectum at Diagnostic Colonoscopy: Subsequent Detection of Extracolonic Malignancies by Plasma Protein Biomarkers?

Introduction: Most of the subjects undergoing diagnostic colonoscopy do not have neoplastic bowel lesions. Potentially, some of the symptoms may therefore be caused by extracolonic malignancy, and subjects with persisting symptoms may need subsequent examinations. Blood-based, cancer-associated biomarkers may aid in directing the examinations for other specific malignant diseases. Methods: EDTA plasma samples available from a previous prospective study of subjects undergoing diagnostic colonoscopy were used for analysis of 18 protein biomarkers. The study population of 3732 subjects included 400 patients with colorectal cancer (CRC) and 177 patients with extracolonic malignancies. Univariable analysis of the association of specific biomarkers and extracolonic cancers included those with 10 or more cases. Subsequently, reduced models of 4 or 6 biomarkers, respectively, were established by choosing those with the highest likelihood; age and sex were included as well. Results: Univariable analyses showed that CyFra21-1 had an area under curve (AUC) of 0.87 for lung cancers (n = 33), CA19-9 had an AUC of 0.85 for pancreatic cancer (n = 22), CA125 had an AUC of 0.95 for ovary cancer (n = 16), B2M had an AUC of 0.81 for non-Hodgkin lymphoma (n = 12), and total prostate-specific antigen had an AUC of 0.99 for prostate cancer (n = 10). The multivariable analysis of 4 or 6 biomarkers plus age and sex as explanatory variables showed AUCs of 0.82 to 0.85 both for extracolonic cancers and CRC. The 4 biomarkers included in the model for detection of extracolonic cancers were CA125, hsCRP, CA19-9, and CyFra21-1; the 2 additional for the 6 biomarkers model were CEA and Galectin-3. Similarly, the 4 biomarkers included in the model for detection of CRC were CEA, CyFra21-1, Ferritin, and HE4; the two additional for the 6 biomarkers model were hsCRP and Pepsinogen 2. Conclusions: Results of this study indicate that it may be possible to detect subjects that have an increased risk of extracolonic cancer following a colonoscopy without findings of neoplastic lesions. Combinations of various protein biomarkers may direct subsequent examination after colonoscopy with clean colorectum. The results, although preliminary, may form the basis for additional research directed both for primary examinations of subjects with symptoms of malignancy and subsequent examinations after colonoscopy.

Extracolonic cancer risk in Dutch patients with APC (adenomatous polyposis coli)-associated polyposis

BackgroundScreening of patients with familial adenomatous polyposis (FAP) have led to a substantial reduction in mortality due to colorectal cancer (CRC). Recent guidelines suggest that surveillance of non-intestinal malignancies should also be considered in those patients. However, the value of these surveillance programmes is unknown. The aims of this study were (1) to assess the occurrence of extracolonic malignancies in a large series of adenomatous polyposis coli (APC) mutation carriers and (2) to evaluate the causes of death.MethodsAll APC mutation carriers were selected from the Dutch polyposis registry. Data on causes of death were collected. Pathology reports were retrieved from the Dutch Pathology Registry.ResultsA total of 85 extracolonic malignancies were diagnosed in 74 of 582 APC mutation carriers. Duodenal and skin cancers were the most prevalent cancers. Thyroid cancer was observed in only 1.5% of the cases. The main cause of death was cancer (59% of all deaths), with 42% due to CRC and 21% due to duodenal cancer. One patient died from thyroid cancer. The second and third most common causes of death were cardiovascular disease (13% of all deaths) and desmoid tumours (11% of all deaths), respectively.ConclusionExtending surveillance programmes to other cancers will not contribute significantly to the survival of patients with FAP.

Molecular diagnosis of hereditary nonpolyposis colorectal cancer (Lynch syndrome)

Lynch syndrome is the most common cause of inherited colorectal cancer, totaling 5 to 8% of all the cases with high susceptibility to this type of cancer and extracolonic cancer. It is related to germinal mutations taking place at mismatch repair genes. The diagnosis of Lynch syndrome is essential for both monitoring patients with this disease and detecting asymptomatic carriers, in order to establish appropriate clinical monitoring, preventive management and genetic counselingAlthough clinical criteria have been standardized by implementing Amsterdam I and II, as well as Bethesda guidelines, the detection rate of mutations in these genes only varies between 20% and 60%.The objective of this research was to review the state of the art regarding molecular diagnosis of Lynch syndrome; thus, a review of the literature published from 1995 to 2015 in PubMed database was performed by using the criteria “lynch syndrome molecular screening”. 19 articles were selected and reviewed, and the relevant bibliography related to such articles was also reviewed.This paper presents different approaches proposed by several researchers on molecular algorithms to improve the efficiency of Lynch syndrome diagnosis.