Carcinoma of large intestine, Colorectal Carcinoma (Adenocarcinoma)

1. Carcinoma of Large Intestine
Lecture16
By
Dr Mohammad Manzoor Mashwani BKMC Mardan
Colorectal Carcinoma
Colonic
Adenocarcinoma

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. 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. 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. 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

7. 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).

10. 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

11. 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

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

13. 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

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

15. Squamous Cell
Carcinoma
Squamous Cell Carcinoma of the anus:
Cancers of the anal zone are
predominantly squamous cell in origin.

16. 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

17. 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

18. 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 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%

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

20. 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

21. Treatment
1.Chemotherapy
2.Radiotherapy
3.Photodynamic therapy
4.Radical surgery
5.Gene therapy