Dataset Information

The All Adenomas study

ABSTRACT: Background and study aims Bowel polyps are small, benign (harmless) growths found on the inner lining of the colon (end part of the large intestine) or rectum. They are not usually cancerous, however if they are found they should be removed as some will eventually turn into cancer if left untreated. People who have been found to have bowel polyps need to undergo surveillance to monitor their growth. Current UK guidelines for the surveillance of people found to have bowel polyps classify people into those who are at low, intermediate or high risk of developing bowel cancer in the future. This guideline was developed in 2002 and now needs to be re-examined. People with intermediate risk bowel polyps are currently recommended to have 3-yearly surveillance colonoscopy (test to look inside the intestine with a camera on a flexible tube). This is likely a good option for some people in the intermediate risk group, but it may not be the best option for others. The aim of this study is to evaluate the effectiveness of the current surveillance guidelines. This study is being extended to assess surveillance in low-risk and high-risk bowel polyp groups. Under the current guidelines, people with low-risk bowel polyps are recommended either no surveillance or colonoscopy at 5 years. In contrast, people with high-risk polyps are recommended to have a colonoscopy at least every three years and maybe more frequently to begin with. The aim of this study is to assess the effectiveness of these guidelines; to understand whether it is safe for people within the low-risk group not to have a colonoscopy, and whether there are people within the high-risk group who do not require such intensive surveillance. The study also re-examines surveillance in the intermediate-risk group with longer follow-up. Who can participate? Men and women of any age who have bowel polyps who have had a colonoscopy What does the study involve? The study uses material from several high-quality databases in hospitals or from bowel cancer screening initiatives to identify groups of patients with bowel polyps. Information from routine colonoscopies conducted to the current surveillance programme is collected and used to see if patient’s polyps worsen or turn into cancer at later visits.

DISEASE(S): Intermediate-risk Adenoma(s) (three Or Four Small Adenomas,Including Those With Low-risk Adenoma(s) (one Or Two Small Adenomas),Or One Or Two Large Adenomas) Or High-risk Adenoma(s) (five Or More Small Adenomas,Or Three Or More Large Adenomas),Patients Diagnosed With Adenomas At Colonoscopy

PROVIDER: 2411262 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Project description:Colorectal cancer often arises from adenomatous polyps. Polyps can grow and progress to cancer, but may also remain static in size, regress, or resolve. Prediciting which progress to cancer and which remain benign is difficult. We developed a long-lived murine model of colorectal cancer with tumors that can be followed by colonoscopy. Our aim was to assess whether these tumors have similar growth patterns and histologic fates to human colorectal polyps to identify features to aid in risk stratification of colonic tumors. Long-lived Apcin/+ mice were treated with 4% dextran sodium sulfate to promote colonic tumorigenesis. Tumor growth patterns were characterized by serial colonoscopy, and pathology was determined. Serial biopsies of tumors were obtained for immunohistochemistry and gene expression profiling by microarray analysis with Affymetrix Whole Genome array. Tumors (n=424) grew, remained static, regressed, or resolved over time with different relative frequencies. Newly developed tumors demonstrated dynamic growth patterns with higher rates of growth and resolution, while more established tumors tended to remain static in size. Colonic tumors were hyperplastic lesions (3%), adenomas (73%), intramucosal carcinomas (20%), or adenocarcinomas (3%). Differentially expressed genes between adenomas and intramucosal carcinomas were identified. We did not identify differentially expressed genes between early and late biopsies from the same tumor. This novel murine model of intestinal tumorigenesis develops colonic tumors that can be monitored by serial colonoscopy, mirror growth patterns seen in human colorectal polyps, and progress to colorectal cancer. Further characterization of cellular and molecular features are needed to determine which features can be used to risk-stratify polyps for progress to colorectal cancer and potentially guide prevention strategies. F1 (SWR x C57BL/6) Apcin/+ mice who had been given two treatments of 4% dextran sodium sulfate in drinking water at weaning underwent colonoscopy around 80 days of age. Those with distal colonic tumors amenable to biopsy had two biopsies taken at that time. Tumors were monitored by colonoscopy every 14 days. Every 28 days, two additional biopsies were taken of each tumor. This protocol was repeated until mice were moribund. Six tumors were removed after sacrifice. The earliest and latest biopsies of each tumor were selected for RNA extraction and Affymetrix hybridization.

Project description:Background and study aims Most bowel cancers develop from adenomas, a type of small growth that grows on the bowel wall. Removing adenomas can help to prevent the development of cancer. The NHS now offers screening for bowel cancer to all men and women aged between 60 and 69 years and from 2010, the age range will be extended to 74 years. The screening test, called FOBT, looks for traces of blood in the stool. People who have a positive FOBT are offered colonoscopy, an examination in which an endoscope is used to examine the lining of the bowel for cancers and polyps. Those who have large or multiple adenomas found at colonoscopy are known to have an increased risk of developing more adenomas and possibly bowel cancer. Therefore they are currently offered surveillance colonoscopy at 3 year intervals. There are a number of problems with this approach. Colonoscopy is a costly procedure requiring a skilled doctor, and it carries a small risk of serious complications. It can miss lesions - indeed most advanced lesions (large adenomas or cancers) found at follow-up examinations were present but missed at the previous colonoscopy. Surveillance colonoscopy is also wasteful of resources because significant lesions are found in only about 3% of examinations, so 97% of surveillance colonoscopies will find either nothing or only small harmless adenomas. This is reassuring to the patient but offers no real benefit. Because more adenomas are now being found as a result of the NHS Bowel Cancer Screening Programme (BCSP), the number of surveillance colonoscopies is increasing and threatens to overwhelm available resources. A more cost-effective way of protecting people with higher-risk adenomas is required. We propose that a new type of stool test (faecal immunological test, FIT) could offer effective protection for this higher-risk group at a fraction of the cost. Only patients who had a positive FIT result would need to be offered colonoscopy. This study is designed to estimate the benefit of this approach. Who can participate? People who have taken part in the Bowel Cancer Screening Programme (BCSP) and have been diagnosed with large or multiple adenomas What does the study involve? Participants are offered the FIT at 1, 2 and 3 years. The test is very simple, requiring participants to collect a tiny amount of stool on a probe and return to the laboratory (easier than the FOBT which requires 6 stool samples). Participants who have a positive FIT result are offered a colonoscopy immediately and their next colonoscopy will be three years later. Those who do not test positive to any of the three annual FITs have their colonoscopy at 3 years in the usual way. We compare the total number of bowel lesions found in people who test positive at the 1st, 2nd or 3rd FITs with the number of lesions found at 3-year colonoscopy in those who had a negative FIT result. If most important lesions are found in the group who have positive FIT results, this would suggests that this new approach could provide effective protection and ultimately mean that colonoscopy could be used only in cases with a positive FIT result.

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The All Adenomas study

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