Colorectal Cancer Ramon Garza III, M.D.

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

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

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

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

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

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

Familial Adenomatous Polyposis

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

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

Polyps Neoplastic Adenomas Non-neoplastic Hyperplastic Inflammatory Juvenile Hamartomatous

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

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

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

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

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)

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

Staging Systems w/ Respect to Depth of Invasion

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

Segmental Resections Right Hemicolectomy Extended Right Hemi

Segmental Resections Transverse ColectomyLeft Hemicolectomy

Segmental Resections RectosigmoidectomyExtended L Hemi

Abdominoperineal Resection

AR LAR/APR APR/Local Excision Rectal Cancers

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.

Gracias