Transcript Colon Cancer by

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
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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
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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
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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
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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
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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
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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.