Physical Address
304 North Cardinal St.
Dorchester Center, MA 02124
Malignant Colorectal and Perianal Disease
I
Colorectal Cancer: Epidemiology
A
Each Year in the United States, 135,000 Cases of Colorectal Cancer will be Diagnosed
- 1.
Colon cancer: 95,000
- 2.
Rectal cancer: 40,000
B
Almost 50,000 People Die of Colorectal Cancer Annually in the United States
- 1.
Mortality is steadily decreasing since 1990.
- 2.
Still the third most common cause of cancer death in the United States
II
Risk Factors
- 1.
Personal history of colorectal cancer or polyps
- 2.
Age—increase in incidence after age 50
- 3.
Family history—up to 20% of patients have family history of colorectal cancers; genetic syndromes account for less than 5% of colorectal cancers.
- a.
Hereditary nonpolyposis syndromes (e.g., hereditary nonpolyposis colorectal cancer [HNPCC])
- b.
Hereditary polyposis syndromes (e.g., familial adenomatous polyposis [FAP], MYH )
- a.
- 4.
Environmental and dietary factors
- a.
Low-fiber, high-fat diet increases risk for colorectal cancer.
- b.
High-fiber, calcium, selenium, vitamins A, C, and E, carotenoids, and plant phenols appear to be protective.
- c.
Cigarette smoking is associated with increased risk, especially more than 35 years of smoking.
- a.
- 5.
Inflammatory bowel disease—after 10 years, the risk for cancer in left-sided colitis or pancolitis is 1%–2% per year. The risk appears to be similar between ulcerative colitis and Crohn proctocolitis.
III
Signs and Symptoms
- 1.
The majority of patients are asymptomatic at presentation.
- 2.
Colon cancer signs and symptoms
- a.
Anemia—microcytic; chronic, intermittent occult blood loss in the stool
- b.
Systemic complaints—anorexia, fatigue, weight loss, or dull, persistent abdominal pain; abdominal mass with more advanced tumors
- c.
Change in bowel habits—obstipation, alternating constipation and diarrhea, small-caliber “pencil” stools
- d.
Obstructive symptoms—less common but more prominent on the left because of growth pattern of tumor, small caliber of bowel, and solid stool
- a.
- 3.
Rectal cancer
- a.
Blood streaking in stools, tenesmus
- b.
This finding must not be attributed to hemorrhoids without further investigation.
- c.
Obstruction is less common but is a poor prognostic sign when present.
- a.
IV
Screening Guidelines for Colorectal Cancer
A
Average-Risk Patient, Starting at Age 50–75 Years—Any of the Following Screening Modalities are Accepted:
- 1.
Colonoscopy every 10 years (preferred method)
- 2.
Annual fecal occult blood test and flexible sigmoidoscopy every 5 years
- 3.
Air contrast barium enema every 5 years
- 4.
Yearly fecal occult blood test
- 5.
Computed tomography (CT) colonography or fecal DNA—promising screening tools for colorectal cancer, but there are insufficient data to conclude screening interval or follow-up at present
B
Inflammatory Bowel Disease—Initial Colonoscopy at Diagnosis
- 1.
Colonoscopy 8 years after diagnosis for pancolitis
- 2.
Colonoscopy 12–15 years after diagnosis of left-sided colitis
- 3.
Colonoscopy every 1–2 years after that
C
Familial Adenomatous Polyposis
- 1.
Colonoscopy yearly starting at 10–12 years of age
- 2.
Yearly flexible sigmoidoscopy to look for evidence of the polyposis
D
Hereditary Nonpolyposis Colorectal Cancer
- 1.
Colonoscopy at 20–25 years of age
- 2.
Repeat colonoscopy every 1–2 years after initial
E
Family History
- 1.
Screening colonoscopy at 40 years of age or 10 years before the age of youngest affected relative
- 2.
Repeat colonoscopy every 5 years after initial
V
Polyps
- 1.
Characterized by histology, presence of dysplasia or cancer, and anatomy (polypoid or sessile)
- 2.
Broadly classified as follows:
- a.
Nonadenomatous: Hyperplastic and hamartomatous polyps have no malignant potential.
- b.
Adenomatous: Adenomas, tubular adenomas, tubulovillous, and villous adenomas are mostly premalignant, although 1%–2% of all polyps will harbor an invasive cancer.
- a.
- 3.
Predictors of invasive carcinoma within a polyp
- a.
Size
- (1)
1–2 cm—2%–9%
- (2)
Larger than 2 cm—20%–50%
- (1)
- b.
Villous or tubulovillous histology
- c.
Left-sided location
- d.
Age greater than 60 years
- a.
- 4.
Haggitt classification of malignant nonsessile polyps:
- a.
Level 0—carcinoma in situ
- b.
Level 1—invasion into submucosa but limited to the head of the polyp
- c.
Level 2—invasion into the neck of the polyp
- d.
Level 3—carcinoma invading stalk
- e.
Level 4—invasion into submucosa below the stalk, or sessile polyps
- a.
- 5.
Management of polyps
- a.
Polypectomy using endoscopic forceps or a snare is appropriate for all polyps found during colonoscopy.
- b.
For adenomatous polyps not amenable to endoscopic treatment (usually because of size or sessile anatomy), biopsies should be obtained and a formal colectomy should be performed if the patient is medically fit for surgery.
- a.
- 6.
Management of malignant polyps removed endoscopically
- a.
Haggitt levels 1, 2, and 3 have less than 1% chance of nodal metastases, and no further therapy is required, except in cases of lymphovascular invasion, poor differentiation, or cancer being present less than 2 mm to resection margin.
- b.
Haggitt level 4 has 12%–25% risk for nodal metastases and requires colectomy.
- c.
Most sessile polyps harboring a malignancy are managed with colectomy.
- a.
VI
Pathogenesis
A
Loss of Heterozygosity Pathway—80% of Cases
- 1.
APC (adenomatous polyposis coli) tumor suppressor gene: first studied in familial adenomatous polyposis. Inactivation/mutation is present in 80% of sporadic colorectal cancers.
- 2.
K-ras —proto-oncogene; mutation leads to uncontrolled cell division
- 3.
DCC (deleted in colorectal carcinoma)—tumor suppressor gene. This mutation is present in more than 70% of colorectal cancers.
- 4.
p53 —gene crucial for initiation of apoptosis. Mutations are present in 75% of colorectal cancers.
B
Replication Error Repair Pathway—20% of Cases
- 1.
Mismatch repair genes include hMSH2, hMLH1, hPMS1, hPMS2, hMSH6/GTPB.
- 2.
Mutations result in microsatellite instability—variable lengths of short-base-pair segments repeated several times
- 3.
Tumors of replication error repair pathway tend to be right-sided and have overall better prognosis.
C
Adenomatous Polyposis Syndromes
- 1.
Familial polyposis—adenomatous polyposis of the colon with a 100% risk for malignancy; may also occur in the stomach and duodenum, including increased risk for ampullary adenocarcinoma; autosomal dominant inheritance. Associated with APC mutation
- 2.
MYH -associated polyposis—similar to an attenuated FAP; fewer polyps; 43%–100% risk of malignancy; increased risk of upper gastrointestinal (GI) polyps; autosomal recessive inheritance. Associated with MYH gene mutation on chromosome 1
- 3.
Gardner syndrome—subtype of FAP, colorectal polyposis associated with extracolonic soft tissue tumors, and osteomas; also has a 100% incidence rate of malignant degeneration
- 4.
Turcot syndrome—polyposis of the colon associated with central nervous system tumors; autosomal recessive inheritance
- 5.
Cronkhite-Canada syndrome—GI polyposis with alopecia, nail dystrophy, hyperpigmentation; minimal malignant potential; no inheritance pattern
D
Nonadenomatous Polyposis Syndromes
- 1.
Peutz-Jeghers syndrome—hamartomatous polyps of the entire GI tract with mucocutaneous deposition of melanin in lips, oral cavity, and digits; hamartomas do not have malignant potential, but increased rate of GI tract cancers are a common comorbidity; autosomal dominant inheritance
- 2.
Juvenile polyposis syndrome—hamartomatous polyps found in the colon and rectum but can be diffuse; hamartomas do not have malignant potential but increase risk for colorectal cancer; autosomal dominant inheritance
E
Nonpolyposis Syndromes
- 1.
Hereditary nonpolyposis syndrome (Lynch syndromes)—replication error repair pathway and the most common inheritable colorectal cancer syndrome account for 2%–7% of all colorectal cancers.
- a.
Lynch syndrome—colorectal cancer, endometrial and ovarian cancer, transitional cell cancer of the ureter and renal pelvis, gastric cancer, pancreatic cancer
- b.
Amsterdam II criteria—assists in the identification of patients who may have Lynch syndrome
- (1)
Three or more relatives with an associated cancer (colorectal cancer, or cancer of the endometrium, small intestine, ureter, or renal pelvis)
- (2)
Two or more successive generations affected
- (3)
One or more relatives diagnosed before the age of 50 years
- (4)
One should be a first-degree relative of the other two.
- (1)
- a.
VII
Preoperative Evaluation
A
You're Reading a Preview
Become a Clinical Tree membership for Full access and enjoy Unlimited articles
If you are a member. Log in here