Carcinoma of Large Intestine
Colorectal Carcinoma

Colonic

Adenocarcinoma
Lecture16
By
Dr Mohammad Manzoor Mashwani BKMC ...
Adenocarcinoma

Adenocarcinoma is a cancer of an epithelium that
originates in glandular tissue, adeno means gland.
• 98% ...
•

EpidEmiology

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

• Adenomas – presumed precu...
Risk Factors for High grade dysplasia and cancer
Large Size - > 1 cm in diameter are risk factor for containing CRC
Villou...
Etiology
•

I. Genetic influences:

– preexisting ulcerative colitis or polyposis syndrome
– hereditary nonpolyposis color...
Pathogenesis
The combination of molecular events that lead to colonic
adenocarcinoma is heterogeneous and includes
Genetic...
•
•
•
•
•

Morphology

25% : in cecum or ascending colon
25%: in rectum and distal sigmoid
25%: in descending colon and pr...
Morphology cont.
• all colorectal carcinomas begin as in situ lesions

• tumors in the proximal colon: polypoid, exophytic...
Morphology cont.
• in the distal colon: annular, encircling lesions that
produce “napkin-ring” constrictions of the bowel ...
Morphology cont.
•

all colon carcinomas

- microscopically similar

• almost all - adenocarcinomas
• range from well-diff...
Morphology cont.
Both forms of neoplasm eventually penetrate

the bowel wall and may appear as
firm masses on the serosal ...
Squamous Cell
Carcinoma

Squamous Cell Carcinoma of the anus:
Cancers of the anal zone are
predominantly squamous cell in ...
Clinical Features
• may remain asymptomatic for years
• symptoms develop insidiously
• cecal and right colonic cancers:
– ...
Clinical features cont.
Anemia in females may arise from gynecologic
causes, but it is a clinical maxim that
iron deficien...
Clinical Features
TNM Staging of Colon Cancer

•
•

spread by direct extension into
adjacent structures and by metastasis
...
Diagnosis
– digital rectal examination
– fecal testing for occult blood loss
– barium enema, sigmoidoscopy and colonoscopy...
Diagnosis cont.
– serum markers (elevated blood levels of
carcinoembryonic antigen)
– molecular detection of APC mutations...
Treatment
1.
2.
3.
4.
5.

Chemotherapy
Radiotherapy
Photodynamic therapy
Radical surgery
Gene therapy
Carcinoma of large intestine, Colorectal Carcinoma (Adenocarcinoma)
Carcinoma of large intestine, Colorectal Carcinoma (Adenocarcinoma)
Carcinoma of large intestine, Colorectal Carcinoma (Adenocarcinoma)
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Carcinoma of large intestine, Colorectal Carcinoma (Adenocarcinoma)

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Carcinoma of large intestine, Colorectal Carcinoma (Adenocarcinoma)

  1. 1. Carcinoma of Large Intestine Colorectal Carcinoma Colonic Adenocarcinoma Lecture16 By Dr Mohammad Manzoor Mashwani BKMC Mardan
  2. 2. Adenocarcinoma Adenocarcinoma 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
  3. 3. • 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.
  4. 4. Risk Factors for High grade dysplasia and cancer Large 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-
  5. 5. 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 fiber 2. corresponding high content of refined carbohydrates 3. high fat content 4. 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
  6. 6. Pathogenesis The combination of molecular events that lead to colonic adenocarcinoma is heterogeneous and includes Genetic & 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).
  7. 7. • • • • • 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
  8. 8. 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
  9. 9. Morphology cont. • in the distal colon: annular, encircling lesions that produce “napkin-ring” constrictions of the bowel and narrowing of the lumen
  10. 10. 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
  11. 11. Morphology cont. Both forms of neoplasm eventually penetrate the bowel wall and may appear as firm masses on the serosal surface
  12. 12. Squamous Cell Carcinoma Squamous Cell Carcinoma of the anus: Cancers of the anal zone are predominantly squamous cell in origin.
  13. 13. 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
  14. 14. 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
  15. 15. Clinical Features TNM Staging of Colon Cancer • • 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 Tumor (T) T0 = none evident Tis = in situ (limited to mucosa) T1 = invasion of lamina propria or submucosa T2 = invasion of muscularis propria T3 = invasion through muscularis propria into subserosa or nonperitonealized perimuscular tissue T4 = invasion of other organs or structures Lymph Nodes (N) 0 = none evident 1 = 1 to 3 positive pericolic nodes 2 = 4 or more positive pericolic nodes 3 = any positive node along a named blood vessel Distant Metastases (M) 0 = none evident 1 = any distant metastasis 5-Year Survival Rates T1 = 97% T2 = 90% T3 = 78% T4 = 63% Any T; N1; M0 = 66% Any T; N2; M0 = 37% Any T; N3; M0 = data not available Any M1 = 4%
  16. 16. Diagnosis – digital rectal examination – fecal testing for occult blood loss – barium enema, sigmoidoscopy and colonoscopy – confirmatory biopsy – computed tomography and other radiographic studies
  17. 17. 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
  18. 18. Treatment 1. 2. 3. 4. 5. Chemotherapy Radiotherapy Photodynamic therapy Radical surgery Gene therapy

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