Sign and Symptoms + Aetiology

Colon cancer
http://emedicine.medscape.com/article/277496-overview

Clinical presentations:
• iron-deficiency anemia
• rectal bleeding
• abdominal pain
• change in bowel habits
• intestinal obstruction or perforation
Right-sided lesions are more likely to bleed and cause diarrhea, while left-sided tumors are usually detected later and could present with bowel obstruction.

Physical examination:
• fatigue, weight loss
• abdominal tenderness
• macroscopic rectal bleeding
• palpable abdominal mass
• hepatomegaly
• ascites


Causes
Multifactorial: genetic factors, environmental exposures (including diet), and inflammatory conditions of digestive tract.

Genetic factors
• Hereditary mutation of the APC gene is the cause of familial adenomatous polyposis (FAP), where affected individuals carry an almost 100% risk of developing colon cancer by age 40 years.
• Hereditary nonpolyposis colon cancer syndrome (HNPCC, Lynch syndrome)
o 40% lifetime risk of developing colorectal cancer
o a cause of about 6% of all colon cancers
o increased risk for urothelial cancer, endometrial cancer
o deficient mismatch repair (dMMR) due to inherited mutation in one of the mismatch repair genes, such as hMLH1, hMSH2, hMSH6, hPMS1, hPMS2

Dietary factors
• higher risk: diet high in red meat and animal fat, low-fiber diet, and low overall intake of fruits and vegetables
• lower risk: folate intake, calcium intake, and estrogen replacement therapy

Lifestyle
• alcohol and tobacco consumption, obesity, and sedentary habits

Inflammatory bowel diseases
• ulcerative colitis and Crohn’s disease
• risk increases with the duration of inflammatory bowel disease and the greater extent of colon involvement
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Rectal cancer
http://emedicine.medscape.com/article/281237-overview

History
• Bleeding (60%)
o often is attributed to other causes (eg, hemorrhoids), especially if the patient has a history of other rectal problems
o Profuse bleeding and anemia are rare
o May be accompanied by the passage of mucus, which warrants further investigation
• Change in bowel habits (43%)
o change is not if capacity of a rectal reservoir can mask the presence of small lesions
o When change does occur it is often in the form of diarrhea, particularly if the tumor has a large villous component
o may have hypokalemia
o may have change in the caliber of the stool
o Large tumors can cause obstructive symptoms
o Tumors located low in the rectum can cause a feeling of incomplete evacuation and tenesmus (Straining, especially long-continued, ineffectual and painful straining, at stool or in urination. Straining at stool is called rectal tenesmus; straining at urination is called vesical tenesmus)
• Occult bleeding via a fecal occult blood test (FOBT) (26%)
• Abdominal pain (20%)
o Partial large-bowel obstruction may cause colicky abdominal pain and bloating
o Back pain is usually a late sign caused by a tumor invading or compressing nerve trunk
o Urinary symptoms may also occur if the tumor is invading or compressing the bladder or prostate
• Malaise (9%)
• Bowel obstruction due to a high-grade rectal lesion (9%)
• Pelvic pain is a late symptom, usually indicating nerve trunk involvement (5%)
• Peritonitis from perforation (3%)
• Jaundice may occur with liver metastases (<1%)

Physical Examination
• attention to size and location of rectal cancer
• possible metastatic lesions, including enlarged lymph nodes or hepatomegaly.
• Digital rectal examination (DRE)
o Assess rectal tumors for size, ulceration, and presence of any pararectal lymph nodes
o Assess fixation of the tumor to surrounding structures (eg, sphincters, prostate, vagina, coccyx and sacrum)
o evaluate patient's sphincter function
• Rigid proctoscopy: to identify the exact location of the tumor in relation to the sphincter mechanism

Causes
Multifactorial: environmental factors, genetic, diet with high fat content.

75% are sporadic and develop in people with no specific risk factors. 25% occur in people with significant risk factors--a family history or personal history of colorectal cancer or polyps (15-20%). Other significant risk factors are certain genetic predispositions, such as hereditary nonpolyposis colorectal cancer (HNPCC; 4-7%) and familial adenomatous polyposis (FAP, 1%); and inflammatory bowel disease (IBD; 1%).

Diet
• Higher risk: high-fat, low-fiber diet
o high in unsaturated animal fats and highly saturated vegetable oils
o Long-term diets high in red meat or processed meats
• Lower risk:
o high fish consumption
o high-fiber diet
 causes the formation of a soft, bulky stool that dilutes carcinogens
 decreases colonic transit time, allowing less time for harmful substances to contact the mucosa
o low animal
o Increased dietary intake of calcium
 bind bile acids and fatty acids
 The resulting calcium salts may have antiproliferative effects, decreasing crypt cell production in the mucosa
o selenium, carotenoids, and vitamins A, C, and E: scavenge free-oxygen radicals in the colon

Alcohol
• more than 30 g daily
• Risk appears greater with beer than with wine

Tobacco
• particularly when started at a young age
• produces toxic polycyclic aromatic amines and the induces angiogenic mechanisms

Following Cholecystectomy
• bile acids flow freely
o increases exposure to the degrading action of intestinal bacteria
o then increases the proportion of carcinogenic bile acid byproducts

Hereditary factors
• Risk
o For offspring, the relative risk is 2.42 (95% CI: 2.20-2.65)
o when more than one family member is affected, the relative risk increases to 4.25 (95% CI; 3.01-6.08)
o If the first-degree family member is younger than 45 years at the time of diagnosis, the risk increase is even higher
• personal history of colorectal cancer or polyps: 30% have synchronous lesions, usually adenomatous polyps. Approximately 40-50% of patients have polyps on a follow-up colonoscopy. Of all patients who have adenomatous polyps discovered via a colonoscopy, 29% of them have additional polyps discovered on a repeat colonoscopy one year later. Malignancy develops in 2-5% of patients. The risk of cancer in people who have had polyps removed is 2.7-7.7 times that of the general population

Genetic disorders
• Familial adenomatous polyposis (FAP)
o autosomal dominant
o development of more than 100 adenomatous polyps and a variety of extra-intestinal manifestations
o The defect is in the APC gene, which is located on chromosome 5 at locus q21
o causes the formation of hundreds of intestinal polyps, osteomas of bone, desmoid tumors, and, occasionally, brain tumors
o Individually, these polyps are no more likely to undergo malignant transformation than are polyps in the general population
o The increased number of polyps, however, predisposes patients to a greater risk of cancer
o If left untreated, colorectal cancer develops in nearly 100% of these patients by age 40
o Whenever the hereditary link is documented, approximately 20% of FAP cases are found to be caused by spontaneous mutation.
• Hereditary nonpolyposis colorectal cancer
o autosomal dominant
o defective mismatch repair genes located on chromosomes 2, 3, and 7
o have the same number of polyps as the general population, but their polyps are more likely to become malignant
o These patients also have a higher incidence of endometrial, gastric, thyroid, and brain cancers

Inflammatory bowel disease
• Cancer risk increases with duration of disease
• Patients should be evaluated for dysplastic changes via an annual colonoscopy. Dysplasia is a precursor of cancer and when present, the risk of cancer is 30%.
• Cancers often develop in areas of strictures and in de-functionalized segments of intestine
• Ulcerative colitis
o After 10 years, the incidence of colorectal cancer is approximately 1% per year
• Crohn’s
o incidence of colorectal cancer 4-20 times greater
o Cancer occurs with at least 10 years' duration
o The average age at cancer diagnosis is 46-55 years
o malignancy is often present in fistulous tracts