Pathogenesis
As mentioned, Colorectal is the second and third most prevalent cancer in men and women, respectively, in the United States. The lifetime risk of a person in the general population for development of Colorectal is about 6%. A number of risk factors have been implicated (Table CONDITIONS THAT PREDISPOSE TO COLON CANCER).
| TABLE. POLYPOSIS SYNDROMES | ||||||||||||||||||||||||||||||||||||||||
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First, merely growing older increases the risk. Over age 40, the annual incidence of colon cancer begins to accelerate, doubling every decade until about age 80. Second, dietary factors, such as a high-fat, low-fiber diet, have been proposed as causative. Third, bowel conditions such as ulcerative colitis, Crohn’s disease, adenomatous polyps, and some of the polyposis syndromes predispose to colon cancer.
Finally, there seems to be a hereditary predisposition to the development of Colorectal. The probability of Colorectal developing in a person who has a first-degree relative with Colorectal is more than 15%, compared to a 6% risk in the general population. In an unusual condition, familial colon cancer syndrome, a high risk of development of colon cancer is inherited in an autosomal dominant manner. These patients may have coexisting adenomatous polyps and may also have melanoma or cancer of the uterus or ovaries. Patients with breast cancer may also have increased risk of developing colon cancer.
| TABLE. CONDITIONS THAT PREDISPOSE TO COLON CANCER | |
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Clinical presentation
History
The most common presenting sign is rectal bleeding, and the most common symptom is change in bowel habit. Unfortunately, these are both late manifestations of the disease. Bleeding may be gross or occult. Occult bleeding typically is detected on routine rectal examination or stool screening tests. A change in bowel habit may be manifested as a decrease in the caliber of the stool if the lesion is distal and constricts the bowel lumen. Patients may complain of constipation. Sometimes diarrhea develops around a partially obstructing lesion.
Mass lesions of the ascending colon, because of the larger diameter of the ascending colon, may grow to a considerable size before symptoms develop. Other possible consequences include anemia, weight loss, anorexia, malaise, abdominal mass, and enterovesical or enterocutaneous fistula. Rarely, the patient may seek treatment initially for symptoms of metastatic disease, such as jaundice or bone pain.
Physical examination may reveal the effects of weight loss, muscle wasting, or anemia. A mass may be evident in the abdomen or by rectal examination. Stool may be positive for gross or occult blood.
Diagnostic studies
A complete blood count should be obtained to evaluate for anemia. Serum iron studies confirm iron deficiency. An elevated serum alkaline phosphatase level, if confirmed to originate in the liver either by fractionation or by the finding of an elevated 5-nucleotidase, suggests liver metastases.
Sometimes an isolated elevation of serum lactic dehydrogenase or Оі-glutamyltranspeptidase is the only indicator of liver involvement. Hyperbilirubinemia in conjunction with an elevated alkaline phosphatase level suggests either extensive liver metastases or obstruction of the external bile ducts by metastatic lymph nodes. Carcinoembryonic antigen may be elevated but is not helpful in making a diagnosis. Its role is largely confined to the follow-up period after primary treatment of the cancer to monitor for recurrence or metastatic spread.
Historically, a barium enema, preceded by flexible sigmoidoscopy, has been used as the first specific diagnostic study. An irregular filling defect or an encircling «apple core» lesion on the barium enema is highly suggestive of adenocarcinoma.
Colonoscopy is the gold standard in the evaluation of the colon for the presence of colon polyps or cancer. Polyps amenable for colonoscopic polypectomy are removed and those that are too large or too sessile to remove are biopsied for histopathologic evaluation.
Virtual colonoscopy, a new radiologic technique, is being developed for screening of the colon for the presence of polyps and cancer; however, it is not yet widely available. If a polyp is seen or suspected, a colonoscopy needs to be performed to confirm its presence and for its removal.
An attempt should be made to identify metastatic disease. A chestx-ray may show pulmonary metastases. If an elevated alkaline phosphatase level appears to be of bony origin, plain bone films or a radioisotopic bone scan may be helpful. A computed tomography scan should be obtained if the alkaline phosphatase elevation originates in the liver, but when liver tests are normal, the value of a preoperative computed tomography scan is controversial.
Differential diagnosis
If a patient has weight loss, blood in the stool, and a mass in the colon, the overwhelming likelihood is adenocarcinoma of the colon. Other considerations include other malignant tumors such as leiomyosarcoma and lymphoma. Sometimes an inflammatory mass caused by diverticulitis or amebiasis mimics colon cancer.
Histopathologically, the differentiation between a large, benign polyp and colon cancer is not difficult.
Treatment and prognosis
Both treatment and prognosis depend largely on how extensively the cancer involves the colon, contiguous structures, and distant sites. The modified Dukes’ classification is in common usage to stage colorectal carcinoma and determine prognosis.
Treatment for Dukes’ A, B, and C lesions is surgical unless operative risk is prohibitive. Rectal cancers usually require an abdominoperineal resection. Preoperative radiation therapy of rectal cancers seems to improve surgical and overall outcome. More proximal cancers are treated by wide resection of the involved segment.
Regional lymph nodes also are removed. Patients with stage D cancers may require palliative resection to control bleeding or to treat or prevent obstruction. Preoperative irradiation, sometimes in conjunction with chemotherapy, has been reported to shift the Dukes’ staging to less extensive disease and improve surgical results.
Chemotherapy and radiotherapy in patients with inoperable cancer have been marginally effective. Radiotherapy of bony metastases may relieve bone pain. Adjuvant chemotherapy of metastatic colon cancer involves the administration of 5-fluorouracil, leucovorin, and irinotecan or a combination of oxiplatin and raltitrexed, which shows promise of survival benefit.
Prognosis
The 5-year survival rate is directly related to the extent of tissue invasion, as indicated by the Dukes’ classification (Table MODIFIED DUKE’S CLASSIFICATION TO STAGE COLORECTAL CANCER). In addition, prognosis and recurrence are adversely affected when tumors are poorly differentiated.
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