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Colon Neoplasia

Colon Neoplasia. Valerie P. Bauer, MD Division of Colon and Rectal Surgery Assistant Professor Department of Surgery UTMB Galveston June 8, 2011. Epidemiology. Common Increasing Incidence Decreasing Mortality. Epidemiology.

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Colon Neoplasia

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  1. Colon Neoplasia Valerie P. Bauer, MD Division of Colon and Rectal Surgery Assistant Professor Department of Surgery UTMB Galveston June 8, 2011

  2. Epidemiology Common Increasing Incidence Decreasing Mortality

  3. Epidemiology • Third most common diagnosed cancer and cause of cancer death annually • 1 million people develop CRC annually • 150,000 cases will be diagnosed in US • Probability of individual developing CRC in US is %6 over a lifetime • Population risk factors • Age • Ethnicity • Race • Socioeconomic status

  4. Etiology Age Dietary Environmental Predisposing medical Conditions: Prior History Colon Cancer or Polyps Inflammatory Genetic

  5. Dietary Risk Factors for CRC • Saturated animal fat • Red meat • High in iron- a pro-oxidant • May increase free radicals that damage mucosa • Charbroiled meat contains aromatic hydrocarbons • Increasing RM consumption by 3.5 oz/ day is associated with 12-17% increased risk of CRC • Fruit and vegetables • Contain anti-oxidants • Studies show no association between high fruit and vegetable consumption and risk reduction for CRC

  6. Dietary Risk Factors for CRC • Fiber • Conflicting data • Increases intestinal transit, decreases exposure to carcinogens • May dilute or absorb carcinogens • Beneficial effect on colon- not rectum • Prostate, Lung, Colorectal, and Ovarian Screening Trial • European Prospective Investigation into Cancer and Nutrition • Calcium • Binds and precipitates bile salts • Beneficial in two randomized double blind placebo controlled trials • 1200mg/ day for 4 years • 2000mg/ day 3 years

  7. Dietary Risk Factors for CRC • Folate (Vitamin B) • Normal DNA methylation • Folate deficiency may disrupt DNA synthesis repair or loss of control of proto-oncogene activity • High intake reduces the risk of CRC • 1998 FDA required folate supplementation of flour, cereals, and grain products • Alcohol • Increased risk for consumption o f 2 or more drinks a day

  8. Environmental • Smoking • Two to three fold increase of adenoma risk in smokers • Defined significant risk as smoking greater than 20 cigarettes for 35-40 years • Mechanism • Generates replication errors • DNA mismatch repair genes

  9. Predisposing Medical Conditions • Inflammatory Bowel Disease • Ulcerative Colitis • 2% risk at 10 years/ 8% at 20 years/ 18% at 30 years • Crohn’s Disease • Cholecystectomy • Bile salt irritation • Increased risk for proximal small bowel and colon malignancy • Ureterosigmoidostomy • Ureterosigmoidanastomosis at risk • 26 year latency period • About 25% will develop neoplasia • Radiation • Acromegaly

  10. Genetic • Hereditary Syndromes • Familial Adenomatous Polyposis • Hereditary Non-Polyposis Colorectal Cancer • Others • Peutz Jehger’s Syndrome • Family History • First degree relative with CRC or adenoma

  11. Molecular Basis of CRC Alterations in regulatory mechanism Mutations transformation

  12. Alterations in Regulatory Mechanisms • Six basic changes 1. Self sufficiency in growth signals 2. Insensitivity to anti-growth signals 3. Evading apoptosis 4. Limitless potential for cell replication 5. Sustained angiogenesis 6. Development of ability to invade and metastasize

  13. Genetic Mutations • Oncogenes • K-ras • most frequently mutated gene in CRC • Involved in transduction of exogenous growth signals • Tumor suppressor genes • Inhibit cellular proliferation or promote apoptosis • Both alleles must be inactivated: Two Hit Theory • APC gene mutation • Adenoma to cancer pathway • Found in 75% of sporadic cases of CRC • Causes hyperproliferation

  14. Adenoma to Carcinoma Sequence Normal epithelium Hyperproliferative epithelium Adenoma Carcinoma DCC K-ras mutation P53 mutations APC mutation

  15. Colon Cancer Screening Average Risk Personal history of adenoma or crc Family history of adenoma or crc Hnpcc Fap ibd

  16. Average Risk • Who is average risk? • No family or personal history of CRC • No symptoms to suggest CRC • No unexplained anemia • No IBD • Recommendations: Begin at age 50 • FOBT annually • Flex sig every 5 years • FOBT and flex sig every 5 years • 15-25% with negative results harbor neoplasia in proximal colon • Air contrast BE every 5-10 years • Detects 50-80% stage I and II adenocarcinoma • Colonoscopy every 10 years • GOLD STANDARD

  17. High Risk: Personal History Adenoma or CRC • Surveillance Colonoscopy is Test of Choice* • Prior adenoma • > 3 adenomas or > 1 large adenoma or high risk lesion calls for repeat within 6 to 12 months • 1-2 small adenomas- repeat in 3-5 years • Prior CRC • Post resection colonoscopy 1 year after surgery and every year thereafter until colon is cleared • Followed by colonoscopy every 3-5 years thereafter

  18. Family History Adenoma or CRC • For patients with first degree relatives diagnosed with CRC: • Screening colonoscopy at age 40, or 10 years before the age of diagnosis of the affected relative

  19. HNPCC • Autosomal dominant inherited disorder • Mutation in MMR genes (genes that code for proteins responsible for correcting errors during DNA replication) • Patients develop CRC between age 40 to 50 • Most tumors are proximal to splenic flexure • Extra-colonic tumors are common • Amsterdam Criteria • 3 family members affected by CRC or HNPCC extra-colonic cancer • 2 generations with one member being a first degree relative of the other • 1 having cancer diagnosis before age 50

  20. HNPCC • Screening colonoscopy • Begins at age 20-25 • Repeat every 1-3 years

  21. FAP • Autosomal dominant • Hundred and thousands of polyps • Cancer before age 40 • Colonoscopy • Puberty • Repeat every 1-2 years

  22. Increased risk for neoplasia 7-8 years after diagnosis for pan-colitis and 12-15 years after dx left colitis • Screening colonoscopy • 7-8 years after initial diagnosis and every 1-2 years thereafter with multiple biopsies to detect dysplasia • 12-15 years for left sided colitis and ever 1-2 years thereafter IBD

  23. Colonoscopy Barium Enema Pedunculated Polyp

  24. VA study • Prevalence 9% • Smaller more aggressive polyp • Formerly a eastern polyp • Best seen after training • High definition • Narrow band imaging • Chromoendoscopy Flat Non-polypoid Polyp

  25. Colon Cancer Evaluation and Staging Clinical presentation Staging and prognostic factors Histologic factors Spreading Patterns

  26. Clinical Presentation • Symptomatic patients • Abdominal pain= MC • Vague and non-specific • Poorly localized • Changes in bowel habits • Depends on the side of the lesion • Possibilities • Pencil thin stool • Mucus in BM • Rectal bleeding • 17.5% patients had colorectal neoplasm in one series 570 patients 50 years or younger undergoing colonoscopy for bleeding • Occult blood in the stool

  27. Preoperative Preparation • Evaluate operative risks • Nutrition • Co-morbidities (CAD, COPD, DM, Steroids) • Localize and confirm tumor • Review colonoscopy • Pathology • Radiography • Stage • CT CAP w/ oral and iv contrast • CEA • Bowel Prep • Controversial • No one likes operating in stool

  28. Staging • Outdated • Dukes • A- Cancer limited to bowel wall • B- Cancer extends to extracolonic tissue • C- Cancer with regional lymph node metastasis • Current Staging System • TNM

  29. Staging: TNM • Tumor • T1- Into submucosa • T2- Into muscularispropria • T3- Through bowel wall • T4- Adjacent structures • Nodes • N1- 1-3 nodes positive • N2- 4 or more positive • Metastasis • M0- no metastasis • M1- Metastasis • Stage I • Any T1 or T2, N0, M0 • Stage II • Any T3 or T4, N0, M0 • Stage III • A- T1 or 2, N1, M0 • B- T3 or 4, N1, M0 • C- Any T, N2, M0 • Stage IV

  30. Histologic Factors • Histologic Grade • Well/ moderately/ poorly differentiated • Mucin Production • Signet-cell • Low curative resection rate • Mean survival 16 months • Venous Invasion • Perineural Invasion • Lymph Node Involvement • Most important prognostic indicator • Need 13 or more for accurate staging • CEA • Correlates with metastatic disease • > 15 mg/ml predicts increased risk of metastasis in otherwise curable colon cancer

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