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Colon Cancer by Bryan E. Mosora, D.O. Prevalence • Third most common cancer in both men and women in the United States • The American Cancer Society estimates that about 104,950 new cases of colon cancer will be reported in 2006 in the United States. • Will cause about 56,290 deaths. Prevalence • Proximal colon carcinoma rates in blacks are considerably higher than in whites and continue to increase, whereas rates in whites show signs of decline. • frequency of colon cancer is the same among men and women Causes • A number of risk factors have been associated with colon cancer. • Colonic polyps, which occur with increasing age, represent a risk for colon cancer development. • Ultimate effect of removing polyps on reducing cancer incidence in the population remains unknown. Polyps Causes • Genetics is a very important risk factor for development of colorectal cancer. • Tobacco smoking is associated with a higher risk of colon cancer • Exercise is believed to reduce the risk of colon cancer Causes • Alcohol consumption is also a risk factor for colon cancer. • Increasing age and a lower intake of total folate have been associated with mutations of a gene found commonly in colorectal cancer. • Diet, and in particular fat content of diet, has been associated with increased risk of colon cancer. Causes • Animal studies have found that dietary beef induces and dietary rye bran prevents formation of intestinal polyps. • Several studies have suggested that red meat and processed meats, through breakdown products, increase DNA damage and cancer risk Causes • As for genetic predisposition, there is a gene on chromosome 5, called the APC gene associated with the familial adenomatous polyposis syndrome. • There are multiple different mutations that occur at this site, yet they all cause a defect in tumor suppression that results in early and frequent development of colon cancer. • This genetic aberration is transmitted to 50% of offspring,each of those affected will develop colon cancer, usually at an early age. Causes • In patients with colon cancer, the p53 gene is mutated 70% of the time. When the p53 gene is mutated and ineffective, cells with damaged DNA escape repair or destruction. • This allows for the damaged cell to perpetuate itself, and continued replication of the damaged DNA may lead to tumor development. • Though these syndromes have a very high incidence of colon cancer, family history without the syndrome is also a substantial risk factor. Causes • • • • • Age Alcohol Diabetes ID 40% increased risk Diet Ethnicity, Race, Social Status Causes • Environment • Exercise • Genetics Diagnosis • Colon cancer often is found by screening and may be completely asymptomatic. • 50% of patients present with abdominal pain, • 35% with altered bowel habits, • 30% with occult bleeding, • 15% with intestinal obstruction Diagnosis • Right-sided colon cancers tend to be larger and more likely to bleed. • Left-sided tumors tend to be smaller and more likely to be obstructing. Diagnosis • • • • • Obtain a family history colon cancer, familial polyposis, ulcerative colitis history of family with colon cancer raises the baseline risk of 2% to 6%. (Most physicians think that this baseline is about 4%.) The presence of a second raises the risk to 17%. Diagnosis • Consider the possibility of cancer of the colon in patients with a fever of unknown origin. • Also in patients with polymyositis Signs • Increased or decreased frequency of bowel movements • Thin stool • Cramping or bloating • Bright red blood on stool Signs • • • • Urge to defecate but no stool Bowel fullness, does not go away with bm Unexplained tiredness Unexplained weight loss Pathophysiology • majority of colorectal cancers are adenocarcinomas. • arise from preexisting adenomatous polyps that develop in the normal colonic mucosa. • molecular genetic alterations have been well studied Mortality/Morbidity • The overall 5-year survival rate from colon cancer is approximately 60%, • Depends upon staging. • staging classification for colon cancer can predict prognosis well. Staging • For Dukes stage A, tumors involving only the mucosa, the 5-year survival rate exceeds 90%, • For Dukes stage B colon cancers, the 5-year survival rate is greater than 70% and can be greater than 80% if the tumor does not penetrate the muscularis mucosa. • Dukes stage C, the tumor has spread to the lymph nodes the 5-year survival rate usually is less than 60%. Staging • Dukes stage D • Modified classification; cancer that has metastasized to distant sites • 5-year survival rate is about 5% More Staging • • • • TNM Classification T= Primary Tumor N= Lymph Node Involvement M= Metastasis to other organs Stage 0 • In Stage 0 the cancer is found only on the innermost layer of the mucosa. • Also called Carcinoma in situ Stage I • In Stage I the cancer has spread to the middle layers of the colon mucosa. • Sometimes referred to as Dukes stage A Stage II • Stage II colon cancer is divided into stage IIA and IIB • Stage IIA: Has spread beyond the middle layer of the colon, or has begun to spread to surrounding tissue. • Stage IIB: Has spread beyond the colon wall or to nearby organs and/or through the peritoneum. Stage III • Divided into Stage IIIA, IIIB, and IIIC • IIIA, cancer has spread to the middle mucosa of the colon, and to as many as 3 lymph nodes • IIIB, cancer has spread to 3 lymph nodes, and either beyond the middle mucosa,to nearby tissues around the colon, or beyond the colon wall into organs or through the peritoneum. • IIIC, cancer has spread to 4 or more lymph nodes, plus one of the above criteria Stage IV • Stage IV cancer has spread to other lymph nodes as well as other parts of the body. • AKA Dukes Stage D Staging Prevention • The effect of either annual or biennial fecal occult blood screening on the incidence of colorectal cancer was evaluated recently in a large prospective randomized case-controlled study of 46,551 individuals in Minnesota. • In the group of patients that was screened by stool guaiac testing, 1 of 6 was positive. • these patients underwent further diagnostic evaluation. Prevention • • • • Barium enema, proctosigmoidoscopy upper GI series colonoscopy Barium Enema Sigmoidoscopy Colonoscopy Prevention • sigmoidoscopy and upper GI series were discontinued part way through the 18-year study • colonoscopy was performed throughout and led to the diagnosis of polyps and cancers Prevention • The incidence of colorectal cancer was found to be significantly reduced in both the annually and biennially screened groups compared to the control group. • Colorectal cancer was detected in 417 of the annually screened group and 435 of the biennially screened group, while 507 cases were detected in the controls (80% and 83% incidence compared to control group, respectively). Prevention • The authors concluded that identification and removal of colorectal cancer precursor lesions (ie, adenomatous polyps) led to reduced incidence of colorectal cancer in the screened groups • Currently, debate exists about when fecal occult blood screening should begin in the general population, as well as about the best screening method. Treatment • Standard therapy for metastatic colon cancer is CPT11 plus 5-FU/leucovorin, also known as the Saltz regimen. • In 2005, the standard therapy for metastatic colorectal cancer is IFL plus bevacizumab (irinotecan, 5-FU, leucovorin, Avastin Treatment • The classic surgical procedure for colon cancer is anterior resection. • The abdomen is explored to determine whether the tumor is resectable, and resection is performed segmentally (eg right or left hemicolectomy) with end-to-end anastomosis. • Total colonic resection is performed for patients with familial polyposis and multiple colonic polyps. Bottom Line • • • • DRE and FOBT each year starting at 50 y/o Sigmoidoscopy or Barium Enema q 5 years Colonoscopy at 50 then every ten years All are moved up depending on risk factors, and can be initiated at 40-45 y/o in high risk patients. References • Barber FD, Mavligit G, Kurzrock R: Hepatic arterial infusion chemotherapy for metastatic colorectal cancer: a concise overview. Cancer Treat Rev 2004 Aug; 30(5): 425-36 • Coia LR, Ellenhorn JDI, Ayoub J-P: Colorectal and anal cancers. In: Pazdur R, Coia LR, Hoskins WJ, et al, eds. Cancer Management: A Multidisciplinary Approach. 4th ed. Huntington, NY: PRR, Inc; 2000: 273-299.