Familial cancer syndromes account for 10% to 15% of colorectal cancers .
Sporadic cancers account for approximately 85% of colorectal neoplasia. Although no inherited genetic mutation can be identified, first-degree relatives of patients with colorectal cancer have a three- to ninefold increase in the risk of developing the disease. Overwhelming evidence suggests that colorectal carcinomas develop from precursor adenomas and are associated with an increasing number of genetic mutations (the so-called Vogelstein progression). A single genetic mutation in the germline of a patient may cause an adenoma to develop. Further mutations in either tumor-suppressor genes or oncogenes are responsible for further development of the adenoma and eventually transformation to neoplasia. Genes implicated in this journey from normal epithelium to carcinoma include K-ras, DCC, and
Environmental factors have also been proposed to play a significant role in the etiology of colorectal neoplasia. Dietary factors that have been shown to increase cancer risk include a diet high in unsaturated animal fats and highly saturated vegetable oils. Increased fiber decreases cancer risk in those on a high-fat diet. Epidemiologic studies indicate that people from less-industrialized countries have a lower risk of colorectal cancer, likely due to dietary differences. This survival benefit disappears in people who immigrate to the United States.
Detection. Surveillance is the periodic complete examination of a patient with known increased risk. Screening is the limited examination of a population with the goal of detecting patients with increased risk.
When to screen for colon cancer ?
Screening of the general population is recommended starting at age 50 years by the American Cancer Society, the American College of Gastroenterology, and the American Society of Colon and Rectal Surgeons. Screening entails either dual-contrast barium enema with sigmoidoscopy or total colonoscopy, and these should be repeated every 10 years if normal or if the patient is not at high risk for colorectal neoplasia. Colonoscopy has a perforation risk of 0.1%, hemorrhage incidence of 0.3%, and mortality of 0.01%. It offers the advantages of obtaining a tissue diagnosis of any abnormality (potentially therapeutic) and greater sensitivity over barium enema. CT colonography is available for those patients unfit or unable to undergo endoscopic evaluation.
Hereditary Colorectal Cancer (CRC) Syndromes
Syndrome % of total CRC burden Genetic basis Phenotype Extracolonic manifestations Treatment Notes Familial adenomatous polyposis (FAP) <1% Mutations in tumor suppressor gene APC (5q21) <100 adenomatous polyps; near 100% with CRC by age 40 yr CHRPE, osteomas, epidermal cysts, periampullary neoplasms TPC with end-ileostomy or IPAA or TAC with IRA and lifelong surveillance Variants include Turcot (CNS tumors) and Gardener (desmoids) syndromes Hereditary nonpolyposis colorectal cancer (HNPCC) 5%–7% Defective mismatch repair: MSH2 and MLH1 (90%), MSH6 (10%) Few polyps, predominantly right-sided CRC, 80% lifetime risk of CRC At risk for uterine, ovarian, small intestinal, pancreatic malignancies Genetic counseling; consider prophylactic resections, including TAH/BSO High microsatellite instability (MSI-H) tumors, better prognosis than sporadic CRC Peutz-Jeghers (PJS) <1% Loss of tumor suppressor gene LKB1/STK11 (19p13) Hamartomas throughout GI tract Mucocutaneous pigmentation, risk for pancreatic cancer Surveillance EGD and colonoscopy q3 yr; resect polyps >1.5 cm Majority present with SBO due to intussuscepting polyp Familial juvenile polyposis (FJP) <1% Mutated SMAD4/DPC (18q21) Hamartomas throughout GI tract; >3 juvenile polyps; 15% with CRC by age 35 yr Gastric, duodenal and pancreatic neoplasms; pulmonary AVMs Genetic counseling; consider prophylactic TAC with IRA for diffuse disease Presents with rectal bleeding or diarrhea
High-risk individuals should be in a surveillance program. Previous cancer or polypectomy increases the risk of metachronous cancer by a factor of 2.7 to 7.7. Routine surveillance has been shown to reduce the incidence of metachronous cancer, although its influence on survival is unknown. High-risk patients are those with (1) ulcerative colitis of more than 10 years’ duration, (2) Crohn or ulcerative colitis with stricture, (3) a history or family history of polyps or cancer, or (4) a family history of adenomatous polyposis (FAP) or hereditary nonpolyposis colorectal cancer (HNPCC). Our surveillance algorithm calls for initial or perioperative colonoscopy followed by yearly examination until no lesions are detected, followed by examination every 3 years until no lesions are detected, and then examination every 5 years.
Peutz-Jeghers syndrome is an autosomal dominant condition characterized by hamartomatous polyps of smooth muscle throughout the GI tract and mucocutaneous pigmentation. Symptoms include bleeding or obstruction secondary to intussusception. Although hamartomas are benign, patients with Peutz-Jeghers syndrome are at increased risk for gastrointestinal adenocarcinoma as well. Therefore, treatment for polyps greater than 1.5 cm in diameter is polypectomy. Surveillance colonoscopy and esophagogastroduodenoscopy (EGD) are recommended every 2 years, as well as periodic screening for breast, cervical, testicular, ovarian, and pancreatic cancer.
Juvenile polyps are cystic dilations of glandular structures in the lamina propria without malignant potential that may result in bleeding or obstruction. There are two peaks in incidence of isolated juvenile polyps: in infants and at age 25 years. They are the most common cause of GI bleeding in children and should be treated with polypectomy. Multiple polyposis coli (diffuse juvenile polyps) is an autosomal dominant syndrome characterized by multiple juvenile polyps and increased risk for GI malignancy. These patients are considered for total abdominal colectomy or proctocolectomy with IPAA.
Hyperplastic polyps show epithelial dysmaturity and hyperplasia and are the most common colorectal neoplasm (10 times more common than adenomas). They have no malignant potential. Most are less than 0.5 cm in diameter and rarely need treatment. However, those showing a mixed adenoma/hyperplastic histology carry the same risks as adenomatous polyps.
Adenomas are benign neoplasms with unrestricted proliferation of glandular epithelium within the colonic mucosa but with no invasion of the basement membrane. The degree of differentiation decreases as a polyp becomes more like a cancer. Severe atypia refers to malignant cells in a polyp that have not invaded the muscularis mucosae (formerly known as carcinoma in situ). Adenomatous polyps fall into three broad categories, based on the percentage of villous composition:
Tubular adenomas are usually pedunculated and account for roughly 85% of adenomas. They have a 5% risk of containing malignant cells.
Tubulovillous adenomas account for 10% of adenomas. They have a 22% risk of containing cancer.
Villous adenomas are usually sessile and account for 5% of adenomas. Both size and induration of the polyp reflect cancer risk. For example, a 4-cm sessile villous adenoma has a 40% risk of cancer, whereas the same polyp with induration has a 90% risk.
What is the treatment?
Treatment consists of colonoscopic removal. Pedunculated polyps have a stalk and can be removed using the cautery snare. Semisessile and sessile polyps may require piecemeal extraction.
The risk of metastatic cancer in regional lymph nodes is 1% in a completely excised, pedunculated polyp in which cancer invades only the head of the polyp, unless there is lymphatic or vascular invasion. These cases may be treated with either colectomy or polypectomy with close follow-up. Invasion of the cancer down the stalk to the lower third requires colectomy.
Sessile polyps containing cancer require colectomy, even if completely excised, because the risk of local recurrence and lymph node metastasis is greater than 10% to 20%.
Villous adenoma of the rectum can present with watery diarrhea and hypokalemia. The risk of cancer in lesions greater than 4 cm with induration is 90%, and transrectal ultrasonography should be used to determine the depth of invasion before excision. Treatment of favorable lesions is by transanal, full-thickness local excision followed by closure of the defect with suture. The role of transanal endoscopic microsurgery (TEM) continues to evolve and has become an accepted approach to rectal villous adenomas. Accurate interpretation of the existing small series of patients with early rectal cancer undergoing TEM is difficult due to heterogeneous inclusion criteria, misstaging of rectal cancer, and varying surgeon experience. If the adenoma is large (>4 cm), circumferential, contains invasive cancer, or is located above the peritoneal reflection (generally 10 cm above the anal verge), a transabdominal proctectomy should be performed.