1. Eugen Divjak Mentor: A. Žmegač Horvat
Colorectal Carcinoma
Eugen Divjak
Mentor: A. Žmegač Horvat
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2. Intestinal tumors
Non-neoplastic Polyps
Hyperplastic polyps
Hamartomatous polyps
Juvenile polyps
Peutz-Jeghers polyps
Inflammatory polyps
Lymphoid polyps
Neoplastic Epithelial Lesions
Benign polyps
Adenomas
Malignant lesions
Adenocarcinoma
Squamous cell carcinoma of the anus
Other Tumors
Gastrointestinal stromal tumors
Carcinoid tumor
Lymphoma
Epithelial tumors of the intestines: major cause of morbidity and mortality worldwide
Colon, including rectum: host to more primary neoplasms than any other organ in the body

3. Adenocarcinoma 98% of all cancers in large intestine
almost always arise in adenomatous polyps, generally curable by resection

4. Epidemiology peak incidence: 60 to 70 years of age
< 20% cases before age of 50
adenomas – presumed precursor lesions for most tumors
males affected ≈ 20% more often than females

5. Epidemiology worldwide distribution
highest incidence rates in United States, Canada, Australia, New Zealand, Denmark, Sweden, and other developed countries

6. Etiology genetic influences:
preexisting ulcerative colitis or polyposis syndrome
hereditary nonpolyposis colorectal cancer syndrome (HNPCC, Lynch syndrome) → germ-line mutations of DNA mismatch repair genes

7. Etiology environmental influences: dietary practices
low content of unabsorbable vegetable fiber
corresponding high content of refined carbohydrates
high fat content
decreased intake of protective micronutrients (vitamins A, C, and E)
use of Aspirin® and other NSAIDs: protective effect against colon cancer?
cyclooxygenase-2 & prostaglandin E2

8. Carcinogenesis
chromosome instability pathway

9. Carcinogenesis
mismatch repair (microsatellite instability) pathway

10. Morphology 25% of colorectal carcinomas: in cecum or ascending colon
similar proportion: in rectum and distal sigmoid
25%: in descending colon and proximal sigmoid
remainder scattered elsewhere
multiple carcinomas present → often at widely disparate sites in the colon

11. Morphology 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
in the distal colon: annular, encircling lesions that produce “napkin-ring” constrictions of the bowel and narrowing of the lumen
both forms of neoplasm eventually penetrate the bowel wall and may appear as firm masses on the serosal surface

13. Morphology 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
cancers of the anal zone are predominantly squamous cell in origin

14. 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
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. TNM Staging of Colon Cancer
Clinical Features
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)
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%
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

16. Clinical Features detection and diagnosis: digital rectal examination
fecal testing for occult blood loss
barium enema, sigmoidoscopy and colonoscopy
confirmatory biopsy
computed tomography and other radiographic studies
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

17. Therapy chemotherapy radiotherapy photodynamic therapy radical surgery
gene therapy

18. True or false?
98% of all cancers in the large intestine are adenocarcinomas.
Use of Aspirin® and other NSAIDs may cause development of colon cancer.
Chromosome instability and the mismatch repair are two carcinogenesis pathways.
Tumors in the proximal colon tend to be annular, encircling lesions that produce “napkin-ring” constrictions of the bowel and narrowing of the lumen, while those in the distal colon tend to grow as polypoid, exophytic masses.
Colorectal carcinoma may remain asymptomatic for years.

19. References: http://www.liebertonline.com/doi/abs/10.1089/pho.2008.2238
Elsevier. Kumar et al: Robbins Basic Pathology 8e