Colon Cancerby

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.