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      Colon Cancer: A Clinician’s Perspective in 2019

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          Abstract

          Colon cancer is a common preventable cancer. With the adoption of widespread colon cancer screening in the developed countries, the incidence and mortality of colon cancer have decreased in the targeted population. But unfortunately, the incidence and mortality of colorectal cancer (CRC) have been increasing over the last 25 years in the young adults below the age of 50. There is disparity in benefit, i.e. reduction in risk of death between right-sided and left-sided colon cancer by screening colonoscopy. The reason could be multifactorial and various measures have been taken to decrease this disparity. Although most of the screened populations are average risk individuals, a minority of the population have various risk factors for developing colon cancer and need to follow specific colon cancer screening guidelines. Gene mutations (adenomatous polyposis coli (APC), deleted in colon cancer (DCC), K-ras, p53, B-Raf proto-oncogene serine/threonine kinase (BRAF), mismatch repair genes) and microsatellite instability lead to the development of colon cancer. Although various non-invasive methods of colon cancer screening are now available, colonoscopy remains the gold standard of colon cancer screening and adenoma detection rate is now being used as the quality metrics in screening colonoscopy. Although Multi-Society Task Force (MSTF) and American College of Physicians (ACP) recommend initiating screening colonoscopy at age 50 years in all individuals except African Americans who should begin screening colonoscopy at age 45 years, the American Cancer Society (ACS) recommends initiating screening colonoscopy at age 45 years in all individuals irrespective of race and ethnicity. Low-volume split-dose prep has been found to be as effective as high-volume split-dose prep and more tolerable to patients with increased compliance. Boston bowel preparation scale is recommended to measure the quality of colon cleansing. CRC is curative if it is diagnosed at an early stage but various palliative treatment options (endoscopic, oncologic and surgical) are available in advanced stages of this cancer. Adequate number of lymph node assessment during surgery is essential in accurate staging of CRC. Checkpoint inhibitors have been found to have dramatic response and durable clinical benefit in dMMR/MSI-H metastatic CRC. Different genetic and immune-oncologic research trials are ongoing for early detection and better management of CRC.

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          Most cited references54

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          Colorectal cancer screening for average-risk adults: 2018 guideline update from the American Cancer Society

          In the United States, colorectal cancer (CRC) is the fourth most common cancer diagnosed among adults and the second leading cause of death from cancer. For this guideline update, the American Cancer Society (ACS) used an existing systematic evidence review of the CRC screening literature and microsimulation modeling analyses, including a new evaluation of the age to begin screening by race and sex and additional modeling that incorporates changes in US CRC incidence. Screening with any one of multiple options is associated with a significant reduction in CRC incidence through the detection and removal of adenomatous polyps and other precancerous lesions and with a reduction in mortality through incidence reduction and early detection of CRC. Results from modeling analyses identified efficient and model-recommendable strategies that started screening at age 45 years. The ACS Guideline Development Group applied the Grades of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria in developing and rating the recommendations. The ACS recommends that adults aged 45 years and older with an average risk of CRC undergo regular screening with either a high-sensitivity stool-based test or a structural (visual) examination, depending on patient preference and test availability. As a part of the screening process, all positive results on noncolonoscopy screening tests should be followed up with timely colonoscopy. The recommendation to begin screening at age 45 years is a qualified recommendation. The recommendation for regular screening in adults aged 50 years and older is a strong recommendation. The ACS recommends (qualified recommendations) that: 1) average-risk adults in good health with a life expectancy of more than 10 years continue CRC screening through the age of 75 years; 2) clinicians individualize CRC screening decisions for individuals aged 76 through 85 years based on patient preferences, life expectancy, health status, and prior screening history; and 3) clinicians discourage individuals older than 85 years from continuing CRC screening. The options for CRC screening are: fecal immunochemical test annually; high-sensitivity, guaiac-based fecal occult blood test annually; multitarget stool DNA test every 3 years; colonoscopy every 10 years; computed tomography colonography every 5 years; and flexible sigmoidoscopy every 5 years. CA Cancer J Clin 2018;68:250-281. © 2018 American Cancer Society.
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            CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer.

            Aberrant DNA methylation of CpG islands has been widely observed in human colorectal tumors and is associated with gene silencing when it occurs in promoter areas. A subset of colorectal tumors has an exceptionally high frequency of methylation of some CpG islands, leading to the suggestion of a distinct trait referred to as 'CpG island methylator phenotype', or 'CIMP'. However, the existence of CIMP has been challenged. To resolve this continuing controversy, we conducted a systematic, stepwise screen of 195 CpG island methylation markers using MethyLight technology, involving 295 primary human colorectal tumors and 16,785 separate quantitative analyses. We found that CIMP-positive (CIMP+) tumors convincingly represent a distinct subset, encompassing almost all cases of tumors with BRAF mutation (odds ratio = 203). Sporadic cases of mismatch repair deficiency occur almost exclusively as a consequence of CIMP-associated methylation of MLH1 . We propose a robust new marker panel to classify CIMP+ tumors.
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              American College of Gastroenterology guidelines for colorectal cancer screening 2009 [corrected].

              This document is the first update of the American College of Gastroenterology (ACG) colorectal cancer (CRC) screening recommendations since 2000. The CRC screening tests are now grouped into cancer prevention tests and cancer detection tests. Colonoscopy every 10 years, beginning at age 50, remains the preferred CRC screening strategy. It is recognized that colonoscopy is not available in every clinical setting because of economic limitations. It is also realized that not all eligible persons are willing to undergo colonoscopy for screening purposes. In these cases, patients should be offered an alternative CRC prevention test (flexible sigmoidoscopy every 5-10 years, or a computed tomography (CT) colonography every 5 years) or a cancer detection test (fecal immunochemical test for blood, FIT).
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                Author and article information

                Journal
                Gastroenterology Res
                Gastroenterology Res
                Elmer Press
                Gastroenterology Research
                Elmer Press
                1918-2805
                1918-2813
                February 2020
                1 February 2020
                : 13
                : 1
                : 1-10
                Affiliations
                132 South 10th Street, Main Building, Suite 468, Philadelphia, PA 19107, USA. Email: monjur.ahmed@ 123456jefferson.edu
                Article
                10.14740/gr1239
                7011914
                32095167
                99cd65ec-0970-49fb-b039-031e37e0ec92
                Copyright 2020, Ahmed

                This article is distributed under the terms of the Creative Commons Attribution Non-Commercial 4.0 International License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 3 November 2019
                : 3 December 2019
                Categories
                Review

                colon cancer,colorectal cancer,screening for colorectal cancer,management of colorectal cancer,colon cancer in young adults

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