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• 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

• 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 ResectionsSegmental Resections

Transverse Colectomy Left Hemicolectomy

Segmental Resections

RectosigmoidectomyExtended L Hemi

Abdominoperineal Resection

AR

LAR/APR

APR/LocalExcision

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