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.