colorectal cancer ramon garza iii, m.d.. colorectal ca dna sequencing mismatch repair genes genomics...
TRANSCRIPT
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