**3. Inflammatory bowel disease**

Patients with long-standing inflammatory bowel disease (IBD) are known to be at an elevated risk of CRC, although it is difficult to precisely estimate the risk. The magnitude of the risk has been studied extensively in ulcerative colitis (UC).

**Ulcerativecolitis—** There is a well documented association between chronic ulcerative colitis and colonic neoplasia, with the extent, duration, and activity of disease being the primary determinants while for Crohn's disease there are less data. However, there is an association between pancolitis due to Crohn's disease and the risk of colon malignancy. The extent of disease does appear to have a significant influence on CRC risk in UC [38]. Other factors that may modify the risk of CRC in patients with UC include the coexistence of primary sclerosing colangitis (PSC), presence of inflammatory pseudopolyps, and severity of inflammation. For patients with long-standing, extensive UC, colectomy is an effective strategy for the prevention of CRC. Other strategies include endoscopic surveillance for dysplasia and/or the use of chemopreventive agents.

The relationship between Crohn's disease and the development of CRC has been less consis‐ tently demonstrated. In studies using data from referral-based practices, the risk of develop‐ ment of CRC appears to be significantly increased in patients with extensive Crohn's colitis. Finally, the risk of CRC in patients with Crohn's disease is elevated, but the exact magnitude of increased risk remains unclear and requires further investigation.

Several additional risk factors have been identified mostly in observational studies. These may include: race/ethnicity and gender, acromegaly, renal transplantation, diabetes mellitus and insulin resistance, use of androgen deprivation therapy, cholecystectomy, alcohol, obesity.

**Protectivefactors** — A large number of factors have been reported by at least some studies to be associated with a decreased risk of CRC. These *include* regular physical activity, a variety of dietary factors, the regular use of aspirin or nonsteroidal antiinflammatory drugs (NSAIDs), and hormone replacement therapy in postmenopausal women. None of these factors are currently used to stratify CRC screening recommendations.

#### **1.** Physical Activity

influence of a more distant family history of CRC on individual risk has not been determined with certainty. Some of the increased risk attributed to family history is due to inheritance of known susceptibility genes, such as mutations in the *APC* gene, *p53* gene, or in MMR genes,

Importantly, the majority of cases of CRC cannot be attributed to known genetic defects even when associated with a family history of CRC as recognized genetic syndromes account for only a small proportion of all cases of CRC. Additional autosomal dominant genetic defects conferring a high risk of CRC almost certainly is found. However, at least some of the increased risk of CRC associated with a family history is likely attributable to other genetic factors, such as recessive susceptibility genes, autosomal dominant genes with low penetrance, or complex

Despite the importance of family history on the risk of CRC, up to 25% of individuals with a first-degree relative with confirmed CRC do not report having such a family history and even those that do report a history may not be aware of the increased risk associated with this. This has important implications for the assessment of family history as well as patient and family

Patients with long-standing inflammatory bowel disease (IBD) are known to be at an elevated risk of CRC, although it is difficult to precisely estimate the risk. The magnitude of the risk has

**Ulcerativecolitis—** There is a well documented association between chronic ulcerative colitis and colonic neoplasia, with the extent, duration, and activity of disease being the primary determinants while for Crohn's disease there are less data. However, there is an association between pancolitis due to Crohn's disease and the risk of colon malignancy. The extent of disease does appear to have a significant influence on CRC risk in UC [38]. Other factors that may modify the risk of CRC in patients with UC include the coexistence of primary sclerosing colangitis (PSC), presence of inflammatory pseudopolyps, and severity of inflammation. For patients with long-standing, extensive UC, colectomy is an effective strategy for the prevention of CRC. Other strategies include endoscopic surveillance for dysplasia and/or the use of

The relationship between Crohn's disease and the development of CRC has been less consis‐ tently demonstrated. In studies using data from referral-based practices, the risk of develop‐ ment of CRC appears to be significantly increased in patients with extensive Crohn's colitis. Finally, the risk of CRC in patients with Crohn's disease is elevated, but the exact magnitude

Several additional risk factors have been identified mostly in observational studies. These may include: race/ethnicity and gender, acromegaly, renal transplantation, diabetes mellitus and insulin resistance, use of androgen deprivation therapy, cholecystectomy, alcohol, obesity.

of increased risk remains unclear and requires further investigation.

interactions between an individual's genetic makeup and environmental factors.

particularly *MSH2*, *MLH1*, and *MSH6*.

10 Colonoscopy and Colorectal Cancer Screening - Future Directions

**3. Inflammatory bowel disease**

chemopreventive agents.

been studied extensively in ulcerative colitis (UC).

counseling.

Over 50 studies have been conducted to evaluate the influence of physical activity on CRC risk. Overall, the literature is relatively consistent with respect to the effect: Greater physical activity (occupational, recreational, or total activity) is associated with a reduced risk of CRC. The effect is relatively small; the estimated increased risk of colon cancer in the sedentary ranges from 1.6 to 2.0. The biological mechanisms that explain the relationship between physical activity and CRC risk are unclear. Increased physical activity leads to changes in insulin sensitivity and IGF levels, and both insulin and IGF are potentially involved with colorectal carcinogenesis. Additional proposed mechanisms include effects of physical activity on prostaglandin synthesis, effects on antitumor immune defenses, and the reduction in percent body fat associated with exercise. The mechanism is almost certainly multifactorial. Nonetheless, for a host of health-related reasons, frequent moderate to vigorous physical activity can be recommended to most patients without hesitation.

**2.** Fruit and Vegetable Intake

The effect of dietary intake of fruit and vegetables on CRC risk has been evaluated extensively [22]. Fruits and vegetables are a source of antioxidants, including carotenoids and ascorbate. Other bioactive constituents in fruits and vegetables that may protect against carcinogenesis include the indoles and isothiocyanates. The evidence for an association between fruit and vegetable intake and the risk of CRC is inconsistent [23]. Given this, it is unlikely that a large number of cases of CRC can be attributed directly to a lack of intake of fruits or vegetables, or that major additional interventions to increase consumption would lead to a substantial reduction in the incidence of CRC.

**3.** Aspirin and Nonsteroidal Anti-inflammatory Drugs

There is considerable observational evidence that the use of aspirin or other nonsteroidal antiinflammatory drugs (NSAIDs) has protective effects at all stages of colorectal carcinogenesis (aberrant crypt foci, adenoma, carcinoma, and death from CRC [14]. The mechanism of antineoplastic action of NSAIDs is incompletely understood, but it is believed that both cyclooxygenase (COX)-dependent and COX-independent pathways may be involved. NSAIDs and aspirin may play an important role in secondary chemoprevention of colorectal adenomas and cancer. Because chemopreventive agents must be used in the general popula‐ tion to substantially reduce the burden of disease, the risks of chemoprophylaxis with aspirin or NSAIDs may outweigh the benefits. Serious GI complications occur in regular users of aspirin and NSAIDs although rare.

#### **4.** Hormone Replacement Therapy

Observational studies have demonstrated an association between hormone replacement therapy (HRT) in women and a reduction in both incidence and mortality from CRC. Possible mechanisms for the effect of HRT include a reduction in bile acid secretion (a potential promoter or initiator of CRC), as well as estrogen effects on colonic epithelium, both directly and through alterations in insulin-like growth factor with the use of estrogens. Overall, there appears to be a consistent reduction in the risk of CRC with the use of HRT. However, given the potential adverse effect of HRT, this should not be used as a primary preventive strategy for CRC.

active or high-pitched bowel sounds suggest gastrointestinal obstruction. A palpable abdomi‐ nal mass is a rare finding that suggests advanced disease. Rectal examination, including fecal occult blood testing (FOBT), is important in the evaluation of possible colon cancer. Rectal cancer may be palpable by digital rectal examination. Other physical findings, although rare, should be systematically searched for, including peripheral lymphadenopathy, especially a Virchow's node in the left supraclavicular space; hepatomegaly from hepatic metastases; and temporal or intercostal muscle wasting from cancer cachexia. Very rare findings with colon cancer include a Sister Mary Joseph node caused by metastases to a periumbilical node, and a

Colorectal Cancer

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http://dx.doi.org/10.5772/53524

Patients with suspected colon cancer should have routine blood tests including a hemogram with platelet count determination, serum electrolytes and glucose determination, evaluation of routine serum biochemical parameters of liver function, and a routine coagulation profile. About half of patients with colon cancer are anemic. Anemia, however, is very common, so that only a small minority of patients with anemia have colon cancer. Iron deficiency anemia of undetermined etiology, however, warrants evaluation for colon cancer, particularly in the elderly [60]. Hypoalbuminemia is uncommon, but not rare, in colon cancer. It usually indicates poor nutritional status from advanced cancer. Routine serum biochemical parameters of liver function are usually within normal limits in patients with colon cancer. Abnormalities, particularly elevation of the alkaline phosphatase level, often indicate hepatic metastases. The serum lactate dehydrogenase level may increase with colon cancer. Diarrhea associated with colon cancer can rarely produce electrolyte derangements or dehydration. Nausea and vomiting from colon cancer can rarely produce metabolic derangements of hypovolemia,

The serum carcinoembryonic antigen level is not useful to screen for colon cancer. It is only moderately sensitive. Although patients with very advanced cancer tend to have highly elevated levels, patients with early and highly curable colon cancer tend to have only mini‐ mally elevated levels, with considerable overlap with the levels of patients without colon cancer. It is poorly specific. Other colonic diseases or systemic disorders can cause a carci‐ noembryonic antigen elevation. Preoperative testing is, however, useful to determine cancer prognosis and to provide a baseline for comparison with postoperative levels. An elevated serum level preoperatively is a poor prognostic indicator: the higher the serum level the more likely the cancer is extensive and will recur postoperatively. After apparently complete colon cancer resection the serum level almost always normalizes; failure to normalize postopera‐ tively suggests incomplete resection. A sustained and progressive rise after postoperative normalization strongly suggests cancer recurrence. Patients with this finding require prompt surveillance colonoscopy to exclude colonic recurrence and abdominal imaging to exclude

Blumer's shelf caused by perirectal extension of the primary tumor.

**4.3. Laboratory abnormalities**

hypokalemia, or alkalosis.

metastases.
