53 COLORECTAL POLYPS
Carlton C. Barnett Jr. M.D., Michael B. Wallace M.D., M.P.H.

1. What are polyps?

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A polyp is an elevation of the mucosal surface that can occur anywhere in the gastrointestinal (GI) tract. Two thirds of polyps occur in the rectosigmoid and descending colon.

2. What are the major types of polyps?

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1. Pedunculated polyps have a head attached by a stalk to the mucosa of the colon or rectum. The stalk usually is covered with normal mucosa.
2. Sessile polyps rest on a broad base.

In both types, the muscularis mucosa is an important landmark for differentiating invasive from noninvasive lesions. Lymphatics and veins do not extend across the muscularis mucosa. Submucosal lesions such as carcinoids and lipomas may resemble colorectal polyps.

3. At what age do polyps occur?

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Adenomatous colorectal polyps occur infrequently under the age of 30 years. The incidence increases with age. However, autopsy series report a microscopic frequency as high as 70% in patients older than age 45 years. The clinical incidence is 25% for persons older than age 60 years.

4. Which polyps have no malignant potential?

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Hyperplastic (metaplastic) polyps are small (1-5 mm) and constitute > 90% of the polyps in the colon and rectum. Unlike adenomatous polyps, hyperplastic polyps are caused by failure of mucosal cells to spread over the mucosal lumen. These cells then accumulate on the luminal surface, forming a polyp.
Hamartomas are collections of normal tissue in abnormal places (within the colonic mucosa).
Inflammatory polyps are common in diseases such as ulcerative colitis, Crohn’s disease, and schistosomiasis. They represent islands of healed or healing mucosal epithelium that are not permanent. The appearance of inflammatory polyps actually reflects the severity of the underlying disease. Lipomas may occur in polypoid form with head and stalk.

5. Which polyps have malignant potential?

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Adenomatous polyps may be precursors for cancer. There are three histologic types of adenomatous polyps. Polyps containing > 75% glandular elements are called tubular, those containing > 75% villous elements are termed villous, and those containing > 25% of both glandular and villous elements are tubulovillous.

6. Are some types of polyps more frequently associated with adenocarcinoma?

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Yes. Villous polyps are “bad actors.” Coutsoftides et al. reported 5.6%, 16%, and 41% incidences of adenocarcinoma in tubular, villotubular, and villous adenomas, respectively.

7. What is the relationship between polyp size and risk of adenocarcinoma?

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Polyps < 2 cm have a 2% risk of containing cancer, 2-cm polyps have a 10% risk, and polyps > 2 cm have a cancer risk of 40%. Sixty percent of villous polyps are > 2 cm, and 77% of tubular polyps are < 1 cm at the time of discovery.

8. What are juvenile polyps?

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Polyps that occur in the colon and rectum of infants, children, and adolescents. Histologically, they consist of large mucus-filled glands with lots of connective tissue. The cause of these polyps is unclear. They may represent a response to inflammation, or they may be hamartomas. Juvenile polyps may present as rectal bleeding or as lead points for intussusception. They should be left alone unless they cause trouble, at which point endoscopic polypectomy is sufficient treatment.

9. How are colorectal polyps diagnosed?

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Fecal occult blood test (FOBT) is the most common test in the United States that leads to the discovery of polyps. Sigmoidoscopy and colonoscopy confirm the diagnosis. Colonoscopy has the advantage of being both diagnostic and potentially therapeutic.
KEY POINTS: COLORECTAL POLYPS

1. A polyp is an elevation of the mucosal surface that can occur anywhere in the GI tract.
2. Hyperplastic polyps are small and constitute > 90% of polyps in the colon and rectum.
3. Polyps containing > 75% glandular elements are called tubular, those with > 75% villous elements are termed villous, and those containing > 25% of both glandular and villous elements are called tubulovillous.
4. Fecal occult blood test is the most common test in the United States that leads to the discovery of polyps.

10. What are the risks of colonoscopy?

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Bleeding and perforation. For diagnostic colonoscopy, these risks are extremely low-1.0% and 0.2%, respectively. Both risks are still < 1% for therapeutic colonoscopy. Bleeding usually stops on its own and rarely necessitates laparotomy.

11. How can one determine whether endoscopic polypectomy is adequate treatment?

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In general, if a margin > 1 mm can be obtained, there is no invasion of the muscularis mucosa, and the histologic grade of the lesion is I or II (well to moderately differentiated), the patient should be offered endoscopic polypectomy. Patients with margins < 1 mm, invasion into vessels or lymphatics, and histologic grade III (poorly differentiated) lesions should undergo colon resection, unless comorbid medical conditions contraindicate surgery.

12. What are the screening recommendations to detect polyps?

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There is broad consensus that persons in otherwise good health should undergo periodic screening for colorectal cancer and polyps beginning at age 50 years in average-risk individuals and age 40 years (or 10 years before the index person’s age) in patients with a family history of cancer (excluding genetic colon cancer syndromes discussed below). Colonoscopy every 10 years is the most commonly used strategy, but FOBT with flexible sigmoidoscopy every 5 years for FOBT-negative patients is permissible. All patients who are FOBT positive and those with adenomatous polyps > 5 mm found on sigmoidoscopy should undergo full colonoscopy. To date, FOBT is the only screening test demonstrated in high-quality randomized clinical trials to reduce the risk of death from colorectal cancer. The risk reduction for death is similar to that of mammography (15-33%), depending how the testing is done. The sensitivity and specificity of FOBT is 40% and 96%, respectively, for colorectal polyps. Sigmoidoscopy and colonoscopy are 90% sensitive and 99% specific for polyps. Sigmoidoscopy, however, does not allow for evaluation of the proximal colon, thus lowering the overall effectiveness of this screening technique. Although colonoscopy is highly effective, it must be performed by trained individuals and carries the risk of anesthesia, thus, compromising its value as a screening tool.

13. What are the screening recommendations for patients with known polyps?

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Patients with low risk (one to three tubular adenomas) should have repeat colonoscopy at 5 years. If patients are found to have multiple polyps or high-grade lesions, they should undergo colonoscopy at more frequent intervals (every 2 years). If patients are found to have no new lesions after one screening cycle, screening can be extended to every 5 years.
Malignant polyps should be removed based on the criteria discussed in question 12. Follow-up endoscopy should be performed at 3 months to ensure that no residual tumor is present at the polypectomy site. After this, follow-up should be the same as for multiple adenomatous lesions.

14. Which clinical syndromes are associated with colorectal polyps?

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Familial adenomatous polyposis (FAP) or adenomatous polyposis coli (APC) is inherited as an autosomal dominant trait characterized by multiple adenomatous polyps throughout the GI tract. Diagnosis is made clinically by observing at least 100 adenomatous polyps in the colon; more than 1000 are found in many cases. FAP is caused by the loss of the APC tumor suppressor gene(s) on the long arm of chromosome 5. Multiple family members often are diagnosed with colorectal cancer, generally at a young age. Bleeding, diarrhea, and abdominal pain are common presenting symptoms. FAP is associated with nearly a 100% risk of cancer. FAP is also associated with small bowel, especially periampullary polyps, cancer, and mandibular osteoma.
Gardner syndrome is also associated with loss of the APC gene. Patients have polyposis, as do patients with FAP, but they also have osteomas of the skull, epidermoid cysts, retinal pigmentation abnormalities, and multiple soft tissue tumors.
Turcot syndrome is also associated with APC mutations and is characterized clinically with central nervous system tumors and multiple adenomatous polyps.
Peutz-Jeghers syndrome consists of multiple hamartomatous polyps throughout the alimentary tract. These polyps are associated with cutaneous melanotic spots on the lips, within the oropharynx, and on the dorsum of the fingers and toes. The malignant potential is very low.

15. What is the natural history of APC?

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In a review of more than 1000 cases of adenomatous polyposis coli, the mean age at diagnosis of polyps was 34 years, and the mean age at diagnosis of colorectal cancers was 40 years. The mean age of death was 43 years. It is now recommended that patients with APC undergo colectomy at age 25 years. Patients are also at risk for the late development of foregut adenocarcinoma. Despite prophylactic total colectomy, this group of patients will not have a normal life expectancy.

16. What are the surgical treatment options for APC?

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Treatment options include total proctocolectomy with permanent ileostomy, abdominal colectomy with rectal preservation, abdominal colectomy with ileorectal anastomosis, and ileal pouch-anal anastomosis. In patients in whom the rectum is preserved, yearly endoscopic surveillance is necessary.

17. What role do genetic defects play in the progression of colorectal polyps to adenocarcinoma?

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The progression of adenomatous polyps to colorectal cancer is believed to involve an accumulation of genetic defects via the activation of protooncogenes or the inactivation of tumor suppressor genes. Colon polyps have provided the best available model of genetic mutations in the progression of normal tissue to cancer. Vogelstein and others have provided an elegant description of genetic events demonstrating that polyps accumulate mutations first in the APC and ras oncogenes. Larger, more advanced polyps carry alterations of a tumor suppressor gene on chromosome 18, and carcinomas are associated with inactivation of the tumor suppressor gene TP53 with coincident loss of function of p53 protein.

18. What role do oncogenes play in the development of adenocarcinoma from adenomatous polyps?

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Oncogenes are copies of normal cellular genes that have been activated by mutation. Activating mutations of one allele of an oncogene can disrupt normal cell growth and differentiation and increase the likelihood of neoplastic transformation. The Ki-ras gene is the most commonly mutated oncogene in sporadic colonic neoplasia. Point mutations in the K-ras gene have been observed in approximately 40% of sporadic colorectal adenomas and carcinomas. Analysis of mutations in DNA from cells shed into the stool has been proposed as a potentially useful way to screen for colorectal cancer. In addition, activation of the tyrosine kinase of the c-src gene product pp60s-src is frequent in polyps of high malignant potential; the activity of tyrosine kinase is significantly elevated above the level of primary tumors in liver metastases.

References
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