Colorectal cancer

Published on 09/04/2015 by admin

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Last modified 09/04/2015

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Chapter 17 COLORECTAL CANCER

• Colorectal cancer is a major health concern with more than one million new cases yearly, and an overall mortality rate of 50% worldwide.

• Surgery is the primary and definitive curative intervention.

• Adjuvant chemotherapy, following curative surgery, is essential in stage III.

• The new standard of adjuvant care is fluorouracil, folinic acid and oxaliplatin for 6 months.

• Combination chemotherapy with biological agents (bevacizumab) is the gold standard in advanced disease.

• Long-term survival for patients with resectable liver and lung metastasis is 30%–40%.

• Combination chemoradiotherapy is mandatory in patients with rectal cancer, preferably prior to surgery.

RISK FACTORS

Environmental and genetic factors can increase the likelihood of developing colorectal cancer (CRC) (Table 17.1). Although inherited susceptibility most strikingly increases the risk, the majority of CRCs are sporadic. Age is a very important risk factor. It rarely occurs before the age of 40, and the incidence begins to increase significantly in the sixth decade, with the highest rate between 65 and 75 years. The incidence rate is higher in industrialised regions, higher in African American than in whites, and it is nearly equal for males and females (M:F ratio1.3:1.0 for rectal tumours).

TABLE 17.1 Risk factors for colorectal cancer (CRC)

Risk factor	Examples	Risk
Genetic disorders	Familial adenomatous polyposis	I
	Hereditary non-polyposis colorectal cancer	I
	Peutz-Jeghers syndrome	I
	Hyperplastic polyposis	I
	Cowden’s syndrome	I
	Juvenile polyposis syndrome	I
Personal history of CRC or adenoma		I
Family history of CRC or adenoma		I
Inflammatory bowel disease	Ulcerative colitis, Crohn’s disease	I
Medications	NSAIDs, aspirin, calcium, vitamin D, statins, hormone replacement therapy (in postmenopausal women)	D
Endocrine disorders	Diabetes mellitus	I
	Insulin resistance	I
	Acromegaly	I
	Obesity	I
	Gastrin	I
Surgical interventions	Cholecystectomy	I
Surgical interventions	Ureterocolic anastomoses	I
Environmental factors	Smoking	I
	Moderate physical activity	D
	Healthy diet (low calorie, rich in fruits and vegetables with low animal products)	D
	Alcohol (moderate and high amount)	I

D = decrease risk for CRC; I = increase risk for CRC; NSAIDs = non-steroidal antiinflammatory drugs.

SYMPTOMS

The majority of patients will present with change in the regular bowel habits, rectal bleeding (rarely melaena) and/or iron deficiency anaemia, abdominal pain, or a combination.

Symptoms may vary according to the site of the tumour. Approximately 25% of the patients have metastatic disease at the time of diagnosis. The most common metastatic sites are the regional lymph nodes, liver, lungs and peritoneum. Ovaries, adrenals, bone, skin and brain may be involved as well. Patients may present with signs or symptoms in any of these organs.

Patients who are symptomatic at the time of diagnosis have a somewhat worse prognosis.

Intestinal obstruction or colonic perforation carries a poor prognosis regardless of the stage of the tumour.

GENETICS

Cancers are all caused by abnormalities in genes, although most cancers are not caused by inherited genetic disorders. Cancer is the result of complex interactions between the fingerprints of the genome and interaction with the environment. For most cancers, the wide variations seen among different national groups appear to be explained almost entirely by environmental factors with familial factors playing a minor role. The exception to this is malignancy in the colon where genetics is much more important. CRC follows three major patterns:

• Sporadic—no family history. This type accounts for about 75% of the cases, and it is most common in subjects older than 50 years. Age, dietary and environmental factors are the most important known risk factors.

• Familial predisposition to CRC. This accounts for about 20% of the cases. Although there is a clear family history of CRC, the pattern is not consistent with any of the inherited syndromes described below. The relative risk for a single affected first-degree relative is 1.7. The risk is further increased if more relatives have CRC, or if affected relatives were diagnosed before 55 years of age.

• Inherited polyposis syndromes—5% of cases are due to these syndromes. This type includes familial adenomatous polyposis (FAP), hereditary non-polyposis colorectal cancer (HNPCC), hamartomatous polyposis syndromes (e.g. Peutz-Jeghers, juvenile polyposis), hyperplastic polyposis and Cowden’s syndrome. These conditions are associated with a very high risk of developing CRC (as well as other tumours outside the gastrointestinal tract), and the genetic mutations underlying many of them have been identified (Table 17.2).

TABLE 17.2 Inherited polyposis syndromes

MULTI-STEP MODEL OF CRC

Specific genetic mutations

The APC (adenomatous polyposis coli) gene on chromosome 5 is the most critical gene in the early development of CRC. Somatic mutations in both alleles are present in 80% of sporadic CRCs. Most sporadic CRCs with wild-type APC have mutations in other genes of the Wnt signalling pathway, mostly in β-catenin.

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