Carcinoma of Large Intestine

Lecture16By

Dr Mohammad Manzoor Mashwani BKMC Mardan

Colorectal Carcinoma

Colonic Adenocarcinoma

AdenocarcinomaAdenocarcinoma is a cancer of an epithelium that originates in glandular tissue, adeno means gland.

• 98% of all cancers in large intestine almost always

arise in adenomatous polyps, generally curable by resection

Epidemiology• Old age: peak incidence: 60 to 70 years of age, < 20% cases before age of 50

• Adenomas – presumed precursor lesions for most tumors

• males affected slightly more (20% )often than females• ↑incidence rates in developed countries-US , Canada, Australia, New Zealand, Denmark, Sweden, • The dietary factors most closely associated with increased colorectal cancer rates are low intake of

unabsorbable vegetable fiber and high intake of refined carbohydrates and fat.• Aspirin or other NSAIDs have a protective effect. Because some NSAIDs cause polyp regression in

patients with FAP in whom the rectum was left in place after colectomy. It is suspected that this effect is mediated by inhibition of the enzyme cyclooxygenase-2 (COX-2), which is highly expressed in 90% of colorectal carcinoma sand 40% to 90% of adenomas and is known to promote epithelial proliferation, particularly in response to injury.

Cancers are most common at the two extremes of age.

Risk Factors for High grade dysplasia and cancerLarge Size - > 1 cm in diameter are risk factor for containing CRC

Villous histology – adenomatous polyps with > 25% villous histology

High-grade dysplasia – adenomas with high-grade dysplasia often coexist with areas of invasive cancer in the polyp.

Number of polyps: three or more(>4) is a risk factor

Familial Cancers of Uncertain Inheritance-

Etiology• I. Genetic influences:

– preexisting ulcerative colitis or polyposis syndrome– hereditary nonpolyposis colorectal cancer syndrome (HNPCC,

Lynch syndrome) → germ-line mutations of DNA mismatch repair genes

II. Environmental influences:

– A. dietary practices

1. low content of unabsorbable vegetable fiber2. corresponding high content of refined carbohydrates3. high fat content4. decreased intake of protective micronutrients (vitamins A, C, and E)

– B. use of Aspirin® and other NSAIDs: protective effect against colon cancer?

• cyclooxygenase-2 & prostaglandin E2

PathogenesisThe combination of molecular events that lead to colonic

adenocarcinoma is heterogeneous and includesGenetic & epigenetic abnormalities. There are sequential multistep mutations in evolution of colorectal

cancer from adenomas by one of the following two mechanisms/Pathways:

• 1. APC mutation/Beta-catenin mechanism (Pathway).

• 2. Microsatellite Instability mechanism (Pathway).

Morphology• 25% : in cecum or ascending colon• 25%: in rectum and distal sigmoid• 25%: in descending colon and proximal sigmoid• 25%: scattered elsewhere• multiple carcinomas present → often at widely

disparate sites in the colon

Morphology cont.

• all colorectal carcinomas begin as in situ lesions

• tumors in the proximal colon: polypoid, exophytic masses that extend along one wall of the cecum and ascending colon

Morphology cont.

• in the distal colon: annular, encircling lesions that produce “napkin-ring” constrictions of the bowel and narrowing of the lumen

Morphology cont.

• all colon carcinomas - microscopically similar• almost all - adenocarcinomas• range from well-differentiated to undifferentiated,

frankly anaplastic masses• many tumors produce mucin• secretions dissect through the gut wall, facilitate

extension of the cancer and worsen the prognosis

Morphology cont.

Both forms of neoplasm eventually penetrate the bowel wall and may appear as firm masses on the serosal surface

Squamous Cell Carcinoma

Squamous Cell Carcinoma of the anus:

Cancers of the anal zone are predominantly squamous cell in origin.

Clinical Features • may remain asymptomatic for years• symptoms develop insidiously• cecal and right colonic cancers:

– fatigue– weakness– iron deficiency anemia

• left-sided lesions:– occult bleeding– changes in bowel habit– crampy left lower quadrant discomfort

Clinical features cont.

Anemia in females may arise from gynecologic causes, but it is a clinical maxim that

iron deficiency anemia in an older man means gastrointestinal cancer until proved otherwise

Clinical Features• spread by direct extension into

adjacent structures and by metastasis through lymphatics and blood vessels

• favored sites for metastasis:– regional lymph nodes– liver– lungs– bones– other sites including serosal

membrane of the peritoneal cavity• carcinomas of the anal region →

locally invasive, metastasize to regional lymph nodes and distant sites

TNM Staging of Colon Cancer

Tumor (T)T0 = none evidentTis = in situ (limited to mucosa)T1 = invasion of lamina propria or submucosaT2 = invasion of muscularis propriaT3 = invasion through muscularis propria into

subserosa or nonperitonealized perimuscular tissue

T4 = invasion of other organs or structures

Lymph Nodes (N)0 = none evident1 = 1 to 3 positive pericolic nodes2 = 4 or more positive pericolic nodes3 = any positive node along a named blood vessel

Distant Metastases (M)0 = none evident1 = any distant metastasis

5-Year Survival RatesT1 = 97%T2 = 90%T3 = 78%T4 = 63%Any T; N1; M0 = 66%Any T; N2; M0 = 37%Any T; N3; M0 = data not availableAny M1 = 4%

Diagnosis– digital rectal examination– fecal testing for occult blood loss– barium enema, sigmoidoscopy and colonoscopy– confirmatory biopsy– computed tomography and other radiographic

studies

Diagnosis cont.

– serum markers (elevated blood levels of carcinoembryonic antigen)

– molecular detection of APC mutations in epithelial cells, isolated from stools– tests under development: detection of abnormal

patterns of methylation in DNA isolated from stool cells

Treatment1. Chemotherapy2. Radiotherapy3. Photodynamic therapy4. Radical surgery5. Gene therapy