Colorectal Cancer Ramon Garza III, M.D.. Colorectal CA DNA Sequencing Mismatch Repair Genes Genomics...
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Transcript of Colorectal Cancer Ramon Garza III, M.D.. Colorectal CA DNA Sequencing Mismatch Repair Genes Genomics...
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Colorectal Cancer
Ramon Garza III, M.D.
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Colorectal CA
• DNA Sequencing• Mismatch Repair
Genes• Genomics• Role of PCR and
FISH in Colon CA
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General Info
• 4th most common malignancy in U.S.• 2nd leading cause of all CA related deaths• Potentially curable with surgery
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Epidemiology
• Industrialized countries have highest incidence rates• Linked to dietary factors
• Decrease in incidence in U.S. 2/2 better screening i.e. colonoscopy
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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
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Neoplastic Progression in Colon CA
Invasive CA = through which layer?
Muscularis Mucosa
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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
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Familial Adenomatous Polyposis
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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
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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
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Polyps
• Neoplastic• Adenomas
• Non-neoplastic• Hyperplastic• Inflammatory• Juvenile• Hamartomatous
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Adenomas
• Tubular Adenomas: 5% invasive malignancy
• Tubulovillous Adenomas: 22% invasive malignancy
• Villous Adenoma: 40% invasive malignancy
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Symptoms
• Intermittent pain• Bleeding• Nausea• Vomiting• Melena• BRBPR• Iron Deficiency
Anemia
• Mechanical Obstruction
• Perforation of Colon• Constipation• Small Caliber Stools• Diarrhea• Incontinence• Tenesmus• Nothing
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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
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Screening
• Age > 50yrs & Average Risk• FOBT annually• Flex Sigmoidoscopy Q5yrs• Colonoscopy Q10yrs• Double Contrast Barium Q5hyrs
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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)
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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
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Staging Systems w/ Respect to Depth of Invasion
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Natural History of Colon CA
Liver is Most Common Site of Distant Mets
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Segmental Resections
Right Hemicolectomy Extended Right Hemi
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Segmental ResectionsSegmental Resections
Transverse Colectomy Left Hemicolectomy
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Segmental Resections
RectosigmoidectomyExtended L Hemi
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Abdominoperineal Resection
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AR
LAR/APR
APR/LocalExcision
Rectal Cancers
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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.
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Gracias