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viii.Improved survival stage for stage compared with those who have sporadic tumors

b.Increased incidence of extracolonic malignancies, including endometrium, ovary, breast, stomach, hematopoietic, small bowel, and skin.

c.HNPCC is caused by a single mutation of a DNA mismatch repair gene. These genes are responsible for maintaining the fidelity of DNA during replication. Alterations in these genes lead to microsatellite instability (MSI), a phenomenon characterized by expansion or deletion of repeated units of DNA. Mismatch repair genes include: hMSH2, hMLH1, hPMS1, hPMS2, hMSH6.

d.Diagnosis of HNPCC is based the Amsterdam criteria, which includes the following:

i.Three or more relatives with histologically verified colorectal cancer, one of whom is a firstdegree relative of the other two.

ii.Colorectal cancer involving at least two generations.

iii.One or more colorectal cancer cases diagnosed before the age of 50.

e.Recommendations for screening in HNPCC:

i.In the absence of genetic testing, first-degree relatives of affected individuals should undergo colonoscopy every 1–2 years beginning at age 20 and yearly past the age of 40.

ii.In known germline mutation individuals, it is recommended that colonoscopy begins either at age 25 or when the age is 5 years younger than the first diagnosed family member, whichever comes first, and should continue annually.

d.Risk factors for colon and rectal cancer: Researchers have identified several risk factors that increase a person's chance of developing colorectal cancer:

1.A family history of colorectal cancer. If there is a first-degree relative (parent, sibling, or offspring) who has had colorectal cancer, the risk for developing this disease is increased.

a.People who have two or more close relatives with colorectal cancer make up about 20% of all people with colorectal cancer.

b.FAP and HNPCC, discussed previously (Chapter 13, IV B), accounts for 5%–10% of patients with colorectal cancer.

2.Ethnic background. Jews of Eastern European descent (Ashkenazi Jews) are thought to have a higher rate of colorectal cancer.

3.A personal history of colorectal cancer, even though it has been completely removed, increases likelihood of developing new cancers in other areas of the colon and rectum.

4.A personal history of colorectal polyps is associated with an increased risk for colorectal cancer. This is especially true if the polyps are numerous or large.

5.A personal history of chronic inflammatory bowel disease including UC and Crohn's disease (CD) increases the risk of developing colorectal cancer (see Chapter 13, VII B 1 and VII C 5).

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6.Age. Chances of developing colorectal cancer increase markedly after age 50. Greater than 90% of people found to have colorectal cancer are older than 50.

7.Diet

a.Diets high in fat, especially from animal sources, can increase the risk of colorectal cancer. It is recommended to eat foods from plant sources and to limit the intake of high-fat foods such as those from animal sources.

b.Fruits and vegetables contain substances that interfere with the process of cancer formation, and their consumption is believed to lower the risk for development of colorectal cancers.

c.Fiber. Eating a diet high in fiber has traditionally been thought to decrease the risk of colorectal

cancer. However, recent evidence suggests that fiber may not be as beneficial as previously assumed.

d.Calcium. It has been observed that increased dietary calcium decreases the incidence of colorectal cancer.

8.Activity. Physically inactive individuals are at increased risk of developing colorectal cancer.

9.Obesity. Risk of dying of colorectal cancer is increased overweight people.

10.Diabetes increases the chance of developing colorectal cancer by 30%–40%. Diabetics also tend to have a higher death rate after diagnosis.

11.Smoking. Smokers are 30%–40% more likely than nonsmokers to die from colorectal cancer. Smoking may be responsible for causing about 12% of fatal colorectal cancers.

12.Alcohol intake. Colorectal cancer has been linked to the heavy use of alcohol.

4.Clinical presentation depends on the location, size, and extent of the tumor.

a.Right-sided cancer

1.Melanotic stools

2.Iron deficiency anemia

3.Right-sided abdominal mass

b.Left-sided cancer

1.Change in bowel habits

2.Passage of red blood via rectum

3.Cramping abdominal pain (caused by partial obstruction)

5.Patient evaluation includes the following:

a.Abdominal examination

b.Rectal examination

1.Digital examination is useful to assess the location, size, and extent of invasion of a tumor in the distal rectum.

a.Hard areas in a tumor suggest carcinoma, whereas soft polyps are more likely to be benign.

b.If a tumor feels fixed or “tethered” to the adjacent pararectal tissues, malignant invasion of the bowel wall is likely.

2.Rigid proctosigmoidoscopy is useful to determine the exact location of a rectal tumor in relation to the anal verge.

3.Endorectal ultrasound provides information concerning the depth of invasion into the bowel wall by a rectal tumor and involvement of lymph nodes.

c.Colonoscopy with biopsy of the lesion and inspection of the remaining colon is necessary to exclude synchronous lesions. A barium enema is often not required if the colonoscopic examination is satisfactory. If the colonoscope does not reach the cecum, a barium enema should be obtained to evaluate the entire colon.

d.Chest radiograph

e.Laboratory studies include carcinoembryonic antigen (CEA); liver enzymes; and hemoglobin, hematocrit, or both.

f.CT scan is used to evaluate the liver and abdomen for metastases and both kidneys for ureteral obstruction.

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6.Treatment. Surgical resection is the preferred treatment for most cases of colorectal cancer. Important aspects of surgery include:

a.Proper preparation of the patient, including bowel preparation

b.Thorough exploration of the abdomen to search for metastases and other intra-abdominal disease

c.Removal of the segment of colon containing the tumor and the lymphovascular pedicle, which contains the lymph nodes that drain the cancer

d.Anastomosis without tension between segments of bowel with satisfactory blood supply

e.Operations for rectal cancer require special considerations.

1.Upper-third lesions (10–15 cm above the anus) can be treated by resection through the abdomen with anastomosis between the left colon and the remaining rectum (low anterior resection).

2.Middle-third lesions (5–10 cm above the anus) are usually amenable to low anterior resection, using circular stapling instruments to fashion the anastomosis.

3.Lower-third lesions. Several options may be considered.

a.Resection of the rectum, anus, and anal sphincters by a combined abdominal and perineal approach requires construction of a colostomy (abdominoperineal resection, also called Miles procedure).

b.Resection of the distal rectum using a transanal approach, resection of the proximal rectum using an abdominal approach, or anastomosis between the colon and distal rectum through the anus can be performed. There are several modifications of these technically difficult operations, and they may be referred to as pull-through operations. In almost all patients, a temporary colostomy is fashioned to allow the anastomosis to heal without the danger of anastomotic leak and sepsis. The colostomy may be closed 10–12 weeks after the initial operation.

c.Local excision, fulguration, and contact radiotherapy may be used for select, very favorable rectal cancers in which the chance of metastases is small, for example:

i.Superficial lesions, freely moveable by digital examination

ii.Those that are not poorly differentiated histologically

iii.Those that are confined to the rectal wall, as detected by endorectal ultrasound

iv.Those in which there are no palpable retrorectal lymph nodes

v.Nonulcerated, exophytic lesions

f.Adjuvant therapy

1.Chemotherapy, as combinations of 5-fluorouracil (5-FU), leucovorin, and more recently oxaliplatin are currently recommended for patients with positive lymph nodes or metastatic disease.

2.Radiation therapy given preoperatively to patients with advanced rectal cancer has been shown to shrink the cancer and reduce local recurrence.

3.Combinations of adjuvant radiation therapy and chemotherapy for advanced rectal cancers are also being employed.

7.Staging. The American College of Surgeons' Commission on Cancer has urged adoption of the TNM staging system. This system identifies the depth of invasion of the tumor (T), the regional lymph node status (N), and the presence of distant metastases (M) (Tables 13-1 and 13-2).

8.Prognosis, determined by 5-year survival, is clearly related to the stage of disease, as demonstrated in Table 13-3.

9.Follow-up

a.Physical examination seldom reveals early tumor recurrences.

b.Colonoscopy should be performed 1 year after surgery to detect any new polyps.

1.If polyps are found and removed, the colonoscopy should be repeated annually until there are no polyps.

2.After a negative colonoscopy, the examination should be repeated every 3–5 years to detect any new polyps.

c.CEA is the most sensitive indicator of recurrent colorectal cancer. CEA is a glycoprotein that is secreted by colorectal tumors. It cannot usually be detected if the tumor has not penetrated

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the bowel wall, and it is often increased if there are metastases. CEA may be elevated in patients with cirrhosis, pancreatitis, renal failure, UC, and other types of cancer and can also be influenced by smoking; thus, measuring the CEA level is a nonspecific test. Most surgeons recommend obtaining CEA levels:

TABLE 13-1 TNM Classification of Colorectal Cancer