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<p>Colonic Polyps: An Overview</p> <p>Prepared by Amr Abdelbadee Abdelhameed Amr Mamdouh Sayed Sixth Year Medical Students, Assiut University Faculty of Medicine Under the Supervision of Dr. Ibrahim Ali Ibrahim Assistant Professor of Surgery, Assiut University Faculty of Medicine</p> <p>Colonic PolypsBackgroundColonic polyps are slow-growing overgrowths of the colonic mucosa that carry a small risk (&lt; 1%) of becoming malignant. However, because colonic polyps are highly prevalent in the general population (especially with increasing age), they confer an important predisposition to colon cancer and are therefore removed when detected. Patients with isolated colonic polyps are usually asymptomatic but can experience overt or occult colonic bleeding. Colonic polyps can occur as part of inherited polyposis syndromes in which their number is greater and the risk for malignant progression is much greater compared to the risk with isolated colonic polyps. In the context of clinical studies of chemoprevention, efforts are being directed at suppressing colonic polyp formation (eg, by use of sulindac) and/or at preventing their progression to colon cancer (eg, by use of aspirin).</p> <p>PathophysiologyColonic polyps, or adenomas, are benign epithelial neoplasms that arise from the epithelial cells lining the colon. Colonic polyps are traditionally divided into 3 groups, as follows: hyperplastic polyps, adenomas, and polyposis syndromes.</p> <p>Hyperplastic polypsHyperplastic polyps comprise about 90% of all polyps and are benign protrusions. They are usually less than 0.5 cm in diameter. Hyperplastic polyps most commonly occur in the rectosigmoid region during adulthood. Thought previously to be entirely clinically insignificant, hyperplastic polyps are now recognized to possess some malignant potential in the setting of hyperplastic polyposis syndrome. Patients who are affected have an occurrence of hyperplastic polyps proximal to the sigmoid colon, with (1) 2 or more that are greater than 10 mm in diameter, (2) a total of more than 30 polyps, or (3) a first-degree relative with the syndrome. The polyps in this syndrome may have adenomatous components; display a serrated, saw-tooth surface epithelium; and harbor methylation of specific target genes, including mismatch repair genes.</p> <p>AdenomasAdenomas comprise approximately 10% of polyps. Most polyps (approximately 90%) are small, usually less than 1 cm in diameter, and have a small potential for malignancy. The remaining 10% of adenomas are larger than 1 cm and approach a 10% chance of containing invasive cancer. Adenomas are traditionally divided by histology into 3 types, as follows: tubular, tubulovillous, and villous. Tubular adenomas are the most common of the 3 types and can be found anywhere in the colon. Villous adenomas most commonly occur in the rectal area; tend to be larger than the other two types; and tend to be nonpedun culated, velvety, or cauliflower-like in appearance. Villous adenomas are associated with the highest morbidity and mortality rates of all polyps. They can cause hypersecretory syndromes characterized by hypokalemia and profuse mucous discharge and can harbor carcinoma in situ or invasive carcinoma more frequently than other adenomas. Thus, the risk of progression to carcinoma is related to both the size and the histology of the adenoma. Adenomas that are greater than 1 cm, contain a substantial (&gt;25%) villous component, or have high-grade dysplasia are commonly referred to as advanced neoplasms and carry an increased cancer risk.</p> <p>The shape or gross structure of the polyp is also clinically significant. Those polyps with a stalk are called pedunculated. Those polyps without a stalk are called sessile. Sessile polyps are more concerning than large pedunculated polyps for two reasons. First, the pathway for migration of invasive cells from the tumor into submucosal and more distant structures is shorter. Second, the complete endoscopic removal is more challenging and more difficult to ascertain. Some premalignant neoplasia is now recognized to be flat, rather than protuberant. Such nonpolypoid neoplasia is more common in the setting of chronic colitis and may be detected more readily by nontraditional endoscopic imaging methods, such as narrow-band width imaging or mucosal staining.</p> <p>Polyposis syndromesPolyposis syndromes are hereditary conditions that include familial adenomatous polyposis (FAP), hereditary nonpolyposis (a misnomer) colorectal cancer (HNPCC)/Lynch syndrome, Gardner syndrome, Turcot syndrome, Peutz-Jeghers syndrome, Cowden disease, familial juvenile polyposis, and hyperplastic polyposis. Progress has been made in understanding some of the genetic factors contributing to the development of these syndromes. Some of the syndromes have extraintestinal features that help differentiate one syndrome from the other. For example, FAP is best understood in terms of the genetic basis and subsequent pathological and genetic events leading to carcinoma. Two other types of benign polyps are hamartomatous polyps, which contain a mixture of normal tissues, and inflammatory polyps, which contain an inflammatory epithelial reaction and are typically found in the context of colitis.</p> <p>EpidemiologyFrequencyUnited States Population and autopsy studies suggest that about 30% of middle-aged or elderly individuals have colonic polyps. In comparison, the incidence of FAP in the United States is 1 case for every 65808300 persons. International Accurate comparison of colonic polyp incidence and prevalence among countries is difficult because of differences in the methods used for detection. Colonic polyp prevalence in patients older than 60 years appears to vary substantially within and among countries, but it appears to be greater than 10% in most areas.</p> <p>Mortality/MorbidityUntreated, colonic polyps can and do progress to carcinoma over several years. Morbidity from colonic polyps is related to complications, such as bleeding, diarrhea, intestinal obstruction, and progression to cancer. Bleeding can be frank hematochezia but is often chronic and goes unnoticed by the patient. If uncompensated, intestinal blood loss can cause anemia, typically due to iron deficiency. A study by Stryker et al suggests that the risk of cancer development from sporadic 1-cm colonic [1] polyps is 8% at 10 years and 24% at 20 years. The risk for cancer development depends on the size of the polyp, villous histology, and its association with polyposis syndromes. In FAP, cancer inevitably develops 10-20 years after the initial appearance of colonic polyps.</p> <p>RaceRace per se is not a major risk factor for colonic polyps. However, studies indicate that blacks have a somewhat higher incidence and an earlier onset of colorectal carcinoma. An American Gastroenterological Association task force recommended beginning colorectal cancer screening in blacks at age 45 years, rather than the standard age of 50 years.</p> <p>SexMales appear to have a moderately higher colonic polyp incidence than females, with earlier onset [2] observed in some studies.</p> <p>AgeColonic polyps are strongly associated with increasing age (typically after age 40 y), but they can occur early in patients with polyposis syndromes. For example, colonic polyps can be detected in adolescents with familial adenomatous polyposis or in patients aged 20-40 years with hereditary nonpolyposis colorectal cancer (HNPCC).</p> <p>Colonic Polyps Clinical PresentationHistoryHistory of present illness Most patients with colonic polyps are asymptomatic. In symptomatic patients, the most common presenting symptom is rectal bleeding. Other symptoms include diarrhea or constipation, often with decreased stool caliber. Villous adenomas of the rectum and distal colon can occasionally manifest as a syndrome of severe diarrhea with massive fluid and electrolyte loss. Chronic bleeding from colonic polyps may cause iron deficiency anemia. Family history: Although colonic polyps are a disease of older individuals, a positive family history of polyposis should prompt referral for screening in younger individuals and, in some cases, at more frequent intervals. A common practice is to begin screening in a patient 5 years earlier than the age at which colonic polyps were diagnosed in a first-degree relative.</p> <p>PhysicalDistal rectal polyps can be detected by digital rectal examination. Otherwise, physical examination findings are typically normal. Occult blood in stools (detected by guaiac and antibody-based tests) may be found in a minority of patients with colonic polyps. Although nonspecific, this finding should prompt a colon evaluation in most patients. Such evaluations have had similar yields of clinically significant findings whether the stool sample was obtained by digital rectal examination or was retrieved from spontaneously passed stools.</p> <p>CausesEpidemiologic studies suggest that environmental causes contribute to differences in colonic polyp incidence in geographically distinct populations, but the responsible factors have remained elusive. Differences in consumption of dietary fiber and antioxidants have been hypothesized to play a role in the development of colonic polyps, but these proposals have not been substantiated in recent studies. There is limited, circumstantial evidence that consumption of meat, fat, and alcohol may be risk factors. Conversely, consumption of calcium and folate may confer a modest protective effect, particularly in patients with a history of colonic polyps and low basal consumption levels.</p> <p>GeneticsA number of polyposis syndromes have been described. These can be associated with specific extraintestinal manifestations as well as extraintestinal tumors. Identification and characterization of the genetic factors leading to the various syndromes is progressing. Most of the mutant genes in these syndromes have been identified. At the genetic level, FAP is understood best. This is an autosomal dominant disorder caused by truncating mutations in the adenomatous polyposis coli (APC) gene. Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disorder caused by mutations in DNA mismatch repair proteins. Cowden disease is associated with mutations in the phosphatase and tensin homology on chromosome 10 (PTEN) protein phophatase.</p> <p>DifferentialsFamilial Adenomatous Polyposis Gardner Syndrome Inflammatory Bowel Disease Peutz-Jeghers Syndrome</p> <p>Colonic Polyps WorkupLaboratory StudiesNo laboratory test can determine definitively whether a given patient has a colonic polyp. A stool occult blood test can detect a fraction (20-40%) of colonic polyps that are greater than 10 mm in diameter but can also reflect other causes of gastrointestinal blood loss. Anemia is not specific for colonic polyps but can be an indication of their presence. A patient with a family history of FAP may inherit a mutation in the APC gene. A blood test may detect this heterozygous state. Because most APC mutations involve truncations of the protein, an in vitro protein [3] truncation assay has been developed by Powell et al. This assay amplifies segments of APC messenger RNA (mRNA) and expresses the protein parts in vitro to readily detect the truncated products. A positive test finding only indicates susceptibility, not the actual presence of a colonic polyp. Genetic testing of blood samples can also detect most cases of hereditary nonpolyposis colorectal cancer (HNPCC)/Lynch syndrome. Despite the name, patients with HNPCC have polyps but many fewer than those patients with APC syndrome.</p> <p>Imaging StudiesAir contrast barium enema This test can detect larger colonic polyps but can miss smaller ones; it has a low falsepositive rate. In a study, air contrast barium enema detected only about 50% of colonic polyps greater than 1 cm in diameter. Virtual colonoscopy This test is performed by CT scanning (or MRI) and has shown promise in research studies, detecting more than 80% of large polyps. In a large, multicenter trial, however, a disappointing sensitivity of only 55% was obtained for colonic polyps 10 mm or larger in diameter. Another trial found a detection rate for CT scanning comparable to colonoscopy, [4] although some methodological issues have been raised regarding this study. Virtual colonoscopy is beginning to be performed for screening outside research settings on limited numbers of patients. Recent data from such screening suggest that virtual colonoscopy results in removal of far fewer polyps that are less than 1 centimeter in [5] diameter than standard optical colonoscopy. Most small polyps have very benign characteristics at the time of removal and may be clinically insignificant. However, some are presumably precursors to advanced polyps. Therefore, their clinical significance, particularly for screening intervals, needs better definition. A main drawback of virtual colonoscopy is that a second procedure, a colonoscopy, is required to remove detected colonic polyps. Whether the radiation exposure from CT [6, 7] scanning may be significant is debated. In most methods, a thorough colon preparation is required. Methods are under development to label stool with barium meals, obviating the need for cathartic bowel prep.</p> <p>ProceduresAdequate bowel cleansing is necessary prior to many procedures. Several preparations are marketed for bowel cleansing (eg, polyethylene glycol 3350 [GoLYTELY, NuLYTELY, HalfLYTELY], magnesium citrate [Citroma], senna [X-Prep]) in preparing patients for gastrointestinal procedures, such as colonoscopy and barium x-ray studies. Recent experience suggests that splitting the preparation in half, with one portion taken the day before the procedure and the second portion taken early on the day of the procedure (eg, completed at least 4-6 h before the procedure) yields more effective cleansing of the right colon. Bowel cleansing preparations may be used with various dietary preparations (eg, clear liquid diet the day before surgery or procedure) and are convenient to administer on an outpatient basis. Nonetheless, distaste for or discomfort from the preparation remains a complaint of some patients. Flexible sigmoidoscopy Flexible sigmoidoscopy is a good screening test and the only procedure or imaging modality to be validated by studies that document a decrease in colorectal cancer mortality. However, this procedure does not examine the entire colon. Studies indicate that the majority of large adenomatous polyps in women will be missed by using flexible sigmoidoscopy alone. Screening is usually begun at age 50 years in patients who are at average risk. Randomized controlled trials have documented a reduction in mortality from colon cancer in populations screened by flexible sigmoidoscopy. However, studies suggest that about 40% of high-risk proximal adenomas remain undetected when this procedure is used as the primary screening modality. Colonoscopy Colonoscopy is the preferred test to detect colonic...</p>