Colorectal Cancer

1. Colorectal Cancer Ramon Garza III, M.D.

2. DNA Sequencing Mismatch Repair Genes Genomics Role of PCR and FISH in Colon CA Colorectal CA

3. General Info • 4th most common malignancy in U.S. • 2nd leading cause of all CA related deaths • Potentially curable with surgery

4. Epidemiology • Industrialized countries have highest incidence rates • Linked to dietary factors • Decrease in incidence in U.S. 2/2 better screening i.e. colonoscopy

5. Etiology • Dietary- Fat intake, low fiber • Molecular Genetics- mutations in oncogenes, tumor suppressor genes, and DNA mismatch repair genes • K-ras- protooncogene -> continuous autonomous cell growth

6. Neoplastic Progression in Colon CA Invasive CA = through which layer? Muscularis Mucosa

7. Molecular Genetics • APC gene- Tumor Suppressor Gene • Familial Adenomatous Polyposis • 100% risk of CA • Mutation of p53- Tumor Suppressor Gene • 75% of sporadic colorectal CA

8. Familial Adenomatous Polyposis

9. Familial Cancer Syndromes • FAP • Autosomal dominant • APC Gene mutation • 1000’s of polyps, average age of CA 42yo • Other sites for CA: Duodenum and Stomach • Osteomas, desmoid tumors and CHRPE • HNPCC • Lynch I- colon CA • Lynch II-colon CA, endometrial, ovarian, gastric, small-bowel, liver, biliary tract, upper urologic tract, and CNS tumors

10. Etiology • IBD • Ulcerative Colitis • Incidence of CA proportional to: • Extent of colonic involvement • Age of onset • Severity and Duration of Disease • 3% CA after 1st 10yrs of onset • 20% during each of next 2 decades • Crohn’s Disease • Likely increased risk of Colon CA

11. Polyps • Neoplastic • Adenomas • Non-neoplastic • Hyperplastic • Inflammatory • Juvenile • Hamartomatous

12. Adenomas • Tubular Adenomas: 5% invasive malignancy • Tubulovillous Adenomas: 22% invasive malignancy • Villous Adenoma: 40% invasive malignancy

14. Intermittent pain Bleeding Nausea Vomiting Melena BRBPR Iron Deficiency Anemia Mechanical Obstruction Perforation of Colon Constipation Small Caliber Stools Diarrhea Incontinence Tenesmus Nothing Symptoms

15. Fecal Occult Blood Tests Colonoscopy w/ 180cm Fiberoptic instrument Can obtain mucosal biopsy and perform polypectomies Diagnostic and Therapeutic 0.1-0.3% severe complications i.e. perforation/hemorrhage Air Contrast Barium Enema Useful when strictures/adhesions present Can visualize right side of Colon Screening

17. Screening • Age > 50yrs & Average Risk • FOBT annually • Flex Sigmoidoscopy Q5yrs • Colonoscopy Q10yrs • Double Contrast Barium Q5hyrs

18. Screening • Age 40yrs w/ 1st degree relative w/ Colon CA/Polyp Dx at 60yo or greater • Start same screening regimen as 50yr olds • Age 40yrs w/ more than one 1st degree relative w/ Colon CA/Polyp or w/ 1st degree relative w/ Colon CA Dx at age <60yo • Start screening at 40yo or 10yrs younger than youngest family member diagnosed • Colonoscopy Q5yrs (normally Q10yrs)

19. Staging • Most Colon CA are adenocarcinoma • Mucin production by tumor = poorer 5yr survival • Most important prognostic factor in Colorectal CA is invasion of primary tumor • The T portion of TNM

20. Staging Systems w/ Respect to Depth of Invasion

21. Natural History of Colon CA Liver is Most Common Site of Distant Mets

22. Segmental Resections Right Hemicolectomy Extended Right Hemi

23. Segmental Resections Transverse Colectomy Left Hemicolectomy

24. Segmental Resections Extended L Hemi Rectosigmoidectomy

25. Abdominoperineal Resection

26. Rectal Cancers AR LAR/APR APR/Local Excision

27. Oncologic Resection • 5cm of normal colon distal and proximal to area of disease • 2.5% have intramural spread beyond 2cm from palpable tumor • Need to take vessels w/ adequate amount of mesentery to include Lymph Nodes • Number of Lymph Nodes required for accurate staging? 12 L.N.

28. Gracias