Good afternoon everyone. First of all, thank you for the organizers for inviting me today. It is my distinct pleasure to present today the Screening and Surveillance Guidelines 2004. So we're all quite aware that colorectal cancer is a highly common disease. In fact, it affects 1.5 million people worldwide annually. It is the third most common cause of cancer among men and the second among women. During this talk, I'm going to be presenting the current screening guidelines both for average risk and also for high-risk patients. I will also be discussing surveillance guidelines specifically for adenomas, serrated polyps, and also colorectal cancer. Adenomatous polyps are the precursor lesions for over 70% of all colorectal cancers. They are classified according to the extent of the villus architecture. The risk of colorectal cancer depends directly on the number of adenomas, the histology of adenomas, and the size at baseline colonoscopy. Low-risk adenomas are those when baseline colonoscopy has one or two tubular adenomas and they're all smaller than 10 millimeters. High-risk are when the polyps are greater or equal than 10 millimeters, three or more adenomas, and they are of villus pathology. Serrated polyps are classified by the WHO into three categories. Hyperplastic polyps, cell-cell serrated adenomas, traditional serrated adenomas. Molecularly, they have been classified as having specific mutation spectrum, methylation of CpG island, BRAC mutation, and also inactivation of the MLH1 with subsequent microcellular instability in their tumors. They account for approximately 20 to 35 percent of all colorectal cancer patients. The enigma with the cell-cell serrated adenomas lies in multiple aspects. For once, they are very difficult to detect, and a meticulous exam, including a specific look at the proximal colon and even a second look, it's been advocated. Cell-cell serrated adenomas are detected anywhere between 2 to 7 percent of average-risk colonoscopies. However, incomplete detection and or missed lesions may account for some of the interval cancers. Today, we have two main colorectal screening guidelines in the U.S. One published by the American Cancer Society and the U.S. Multi-Society Task Force, and the second one by the U.S. Preventive Services Task Force, that is the one that uses Medicare to provide coverage. They were both published in 2008. The first of the guidelines, which I'm going to discuss, are those by the ACS and U.S. Multi-Society Guidelines, which divide the type of tests into main categories. Those tests that can detect adenomatous polyps and cancer, and those include flexible sigmoidoscopy every five years, colonoscopy every 10 years, double contrast baromedema every five, and CT colonography every five years. The second category of tests are those that primarily detect cancer, and there it is included the annual WIAC-based Fecal Cold Blood Testing, the FITs, and the stool DNA tests with an interval of uncertain at this point. When you look at the second set of guidelines, which was provided by the U.S. Preventive Services Task Force, this is the first time that age is used to classify the individuals that should undergo screening. Individuals between the ages of 50 to 75 should be screened routinely with three methods, either high-sensitivity FOBT, sigmoidoscopy, or colonoscopy. As you can see, neither the CT colonography or the stool DNA were included in that reiteration of the guidelines. We do know that colonoscopy decreases colorectal cancer mortality, and I want to highlight this paper by Linda Robnick and her group, where 2.5 million Canadians were evaluated. The group consisted of a cohort between ages of 50 to 90, and in this elegant study they show that with every 1% increase in colonoscopy use, the risk of death from colon cancer dropped by 3%. How about stool DNA testing? This article was just published last month in the New England Journal of Medicine that evaluated a new multi-target stool DNA testing for colorectal cancer screening. This was a truly asymptomatic screening cohort consisting of close to 10,000 individuals that underwent screening colonoscopy. The ages between 50 to 84, no history of cancer, inflammatory bowel disease, and the panel consisted of a group of markers including several KRAS mutations, two genes that were methylated, the beta-actin, and the fecal immunological testing. They identified in that cohort of close to 10,000 people, 65 with colorectal cancer and 767 with advanced neoplasia. These are the results. So in this graph, we present the different stages from stage 1 to stage 4, and in the light blue you see the multi-target DNA tests compared to the fit. You can see that for both stage 1 and stage 2 colorectal cancer, the multi-target DNA test was superior. So the sensitivities were higher among those two first categories, and it remained similar throughout every stage. However, the specificities for this multi-target DNA was smaller, so 89 as compared to above 96, and specificities were worse with advanced age of the cohort. This actually is quite interesting. They evaluated high-grade dysplasia, as you can see there, and again the multi-target DNA tests showed higher sensitivity as compared to the FIT, but of note, 40% sensitivities were observed for sessile serrated polyps as compared to only 5% sensitivity with the regular FIT. Colorectal cancer screening for high-risk individuals is highly dependent on the family history of that individual, that is family history of colorectal cancer, and personal risk of the individual. So if your patient has one FDR diagnosed with colorectal cancer after the age of 60, the recommendation is to undergo screening as average risk individuals starting at age 50. If there's one FDR diagnosed with colorectal cancer before the age of 60 or multiple family members, that is first-degree family members, the recommendation is to start at age 40 or 10 years before the age of diagnosis, repeating every five years. If your patient has Lynch syndrome or HMPCC, the recommendation is to start between the ages of 20 to 25 and repeat every two years until age 40, then every year thereafter. For patients with ulcerative or Crohn's colitis, the recommendations are to be stratified according to the years since the diagnosis and the extent of the disease, and then repeat annually. For Lynch syndrome, I just want to mention this, there has been shown that the use of colonoscopy every two to three years has been associated with a decrease in colorectal cancer among Lynch patients. In fact, this has been shown in the Finnish cohort, in the German consortium, and also in the U.S. consortium. Let's now switch gears and talk about colorectal cancer surveillance. Colonoscopy surveillance intervals are really based on evidence supporting decrease in colorectal related mortality and also decrease in interval cancers. What are the interval cancers? Those that develop after a colonoscopy and before the next surveillance colonoscopy. It's believed that it results from multiple factors, including new fast-growing lesions, but more recently the data appears to support that incomplete removal of the lesions and missed lesions account for most of those interval cancers. In fact, a very recent article that was published last month in New England showed an inverse relationship between the ADR and the interval colorectal cancer. That is, as the ADR increased, the interval colorectal cancer decreased and that was of high statistical significance. These are the surveillance guidelines published in 2002 in Gastro that are based in a stratified concept on the baseline colonoscopy where the most advanced finding is used to determine the surveillance interval. In gray, you can see that patients that had no polyps on the baseline colonoscopy had a follow-up at 10 years. Those that had hyperplastic polyps, usually in the left side, less than 10 millimeters, they had a 10-year follow-up. One or two tubular adenomas less than 10 millimeters, they had a range between 5 to 10 years, but most experts are aligning to, you know, longer follow-up, 6, 7, or 8 years. In yellow, you see the mid-category risk, and here three years are recommended for individuals that have a baseline colonoscopy with tubular adenomas between 3 to 10, large tubular adenomas, those greater or equal than 10 millimeters, villus adenoma, or adenoma with high grade displacement. In orange, you see the high-risk category, so either patients that have 10 or more adenomas at baseline, those that have facemale resection of their polyps or the cancer, and of note, if an individual has 10 or more adenomas, and that should also be considered in multiple colonoscopy, recommendation for evaluation for genetic predisposition, it's included. How about serrated polyps? This guidance provided a full section on serrated polyps surveillance, and again, the risk is stratified, high, moderate, low, and very low. In the high-risk category, those are individuals that had multiple polyps, and that's known as the hyperplastic polyposis syndrome, with five or more sessile serrated adenomas proximal to the sigmoid colon, and two of them larger than 10 millimeters. For those individuals, an interval of one year is recommended. Moderate risk are those individuals that had serrated polyps with dysplasia, or those individuals that had serrated polyps with the size of greater or equal than 10 millimeters. For those, three-year interval follow-up. Low risk in the serrated polyp category, for those that had no dysplasia located in the proximal colon, and for them, five-year surveillance interval. And then the very low risk, which are the classic hyperplastic polyps, with a follow-up colonoscopy interval at 10 years. How about second surveillance program? Once a patient has a high-risk adenoma, at any exam, the risk of having a subsequent high-risk adenoma is higher. The follow-up for patients after they undergo the surveillance, it's still uncertain, but the guidelines provide some idea for follow-up. So for individuals that have a low-risk adenoma at baseline, and on the first surveillance they have a high-risk adenoma, the interval is at three years. If the first surveillance shows a low- risk adenoma, the interval is five years, and if the follow-up or the first surveillance shows no adenoma, they go back to 10 years. However, in individuals that you start with a high-risk adenoma, and on the first surveillance you also have a high-risk adenoma, the follow-ups in three years, but for those that start with a high-risk adenoma and they have no adenoma, the surveillance is to continue in five years. I want to finalize with this article that was published a few months ago by the European Society of Gastrointestinal Endoscopy that talked about imaging recommendations for detection of colorectal neoplasia, and basically the statement recommended certain equipment, and high-definition was included, for average-risk individuals. NBI and or chromendoscopy was recommended for patients with Lynch syndrome are those with sessile serrated polyposis. Chromendoscopy with indigo carmine or methylene blue was recommended for surveillance of ulcerative colitis. Chromendoscopy was recommended for prediction of risk of invasive cancer and submucosal invasion, and finally, it was recommended for real-time optical diagnosis of those polyps that were smaller than five millimeters to replace histopathological diagnosis. To summarize, stratified baseline colorectal cancer risk screening, to determine the best screening method and interval. For patients with family history, colonoscopy is the only alternative. For those that already have polyps, also colonoscopy is the only method that should be recommended. Stool-based methods are effective for average risk and may increase adherence, and the FDA should be evaluating the new method, the multi-DNA target, as long as, in addition to other methods, in the next few months, so we will know very soon if this is approved. Finally, intervals of surveillance should adhere to evidence-based guidelines, and use of enhanced digital imaging or chromendoscopy for high-risk individuals, including those with Lynch syndrome, cell-serrated polyposis, and ulcerative colitis. Thank you.

Screening and Surveillance Guidelines 2004

colorectal cancer

adenomatous polyps

colorectal screening guidelines

enhanced imaging techniques