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COLORECTAL CANCER

COLORECTAL CANCER. STATISTICS RISK ASSESSMENT SCREENING OPTIONS Luke Crantock. How Common is Bowel Cancer ?. 14,410 new cases diagnosed in 2010 More common in Men 1 : 17 M, 1 : 26 F

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COLORECTAL CANCER

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  1. COLORECTAL CANCER • STATISTICS • RISK ASSESSMENT • SCREENING OPTIONSLuke Crantock

  2. How Common is Bowel Cancer ? • 14,410 new cases diagnosed in 2010 • More common in Men 1 : 17 M, 1 : 26 F • 7982 ( M), 6428 (F ) – 12.6% all new cancers

  3. Rare before the age of 50 ( 7.6 % of all CRC’s ) • Risk at 85 is 1 : 12 • Incidence - increased in men from 66.7/10 000 in 1982 to 72/100 000 in 2009 , women stable at 50/100 000.

  4. MORTALITY • Second most common cancer death : 14% ( Lung 20% ) • 2010 : 3982 deaths from CRC • 80 Australians dying from cancer /week – one death every 2 hours • Mortality rate has decreased from 31.5/100 000 in 1982 to 16.2 /100 000 in 2010 • Risk dying from cancer at age 85 is 1: 45

  5. Number of deaths from commonly occurring cancers In Australia 2010

  6. 5 YEAR SURVIVAL ACPS, pTNM • A : Localised within bowel : 80-90 %- • B : Penetrates wall : 55-80 % • C : Regional nodes : 40% • D : Distant metastases : 8 -10 % • Early detection is essential, survival relatively good compared to other cancers such as stomach, lung pancreas etc • Fewer than 40 % cancers are detected early

  7. Aetiology • Interaction between inherited susceptibility and environmental factors leading to accumulation of mutations in DNA resulting in uncontrolled cell growth • Benign precursor lesion – Adenoma • Sequential multistep process involving damage to genes leads to invasive malignancy

  8. How Common are Polyps ? • 50 Yrs : 30% • 60 yrs : 40-50 % • 70 Yrs : 50-65 % • Risk family history Adenoma similar to CRC • Serrated adenoma ( Methylation )

  9. All in the Genes • Gene changes may be acquired ( diet, age etc ) or inherited. • Tumours suppressor genes ( protective ) - acquired or inherited • DNA repair genes - acquired or inherited • Oncogenes – activation of ( K-ras ) - acquired

  10. 1990 Fearon & Vogelstein proposed multistep hypothesis for tumorigenesis particularly p53 and APC genes involved

  11. RISKS - CRC • Age ( low before 50yrs -7.6 %) • Family History • Medical History ( polyps , IBD ) • Environmental Factors Up to 75 % of CRC could be prevented by improvements in diet , activity and screening

  12. CRC risk -median age Dx 70 • At 5 yrs 10 yrs 20 yrs • 30 1: 7000 1: 2000 1: 350 • 40 1: 1200 1: 400 1: 90 • 50 1: 300 1: 100 1: 30 • 60 1: 100 1: 50 1: 20 • 70 1: 65 1: 30 1: 15 • 80 1: 50 1: 25

  13. RELATIVE RISK • Average risk ( 75% have no family history ) • Slight increased risk – 2nd degree relative – 1.3 times • Low Risk – 1st degree relative ( eg parent ) with CRC older than 55 - 2 times risk

  14. Moderate Risk- One relative less than 55 yrs or Father and grandfather , (one younger than 50 risk) 3-6 times • High Risk – FAP, HNPCC syndromes, “3,2,1 “ rule – 3 relatives ( one first degree ), 2 generations , one less than 50yrs. 80% risk of CRC, 40-60% endometrial or ovarian cancer

  15. Medical History • Past Hx Polyps • Past Hx CRC • Hx IBD

  16. Lifestyle factors-Prevention • Healthy Lifestyle – Physical activity – Healthy BMI – Limit alcohol – Quit smoking

  17. Lifestyle & Diet, • Regular activity 30-60min/day • NHMRC attributes dietary factors to 50% CRC • Reduce daily energy intake < 2000 calories/day for men, < 2000 calories /day for women. • Increased risk Type 2 Diabetes • Reduces fats - Exception is omega-3 fatty acids inverse correlate –reduce epithelial proliferation • Limit alcohol <2 std drinks/day

  18. Lifestyle & Diet • 5 or more serves vegetables/day • 2 serves fruit/day • Encourage cereals • Lean meats, avoid charring & processed meats • Stop smoking ( 50% increased risk ) • Folate, Selenium • Aspirin, NSAIDS • HMG-Co A reductase inhibitors • 1000-1200mg calcium/day

  19. Patient Assessment • Any family members with CRC ? ( 75 % do not ) • Any family members with polyps ? • Any previous polyps ? • Any rectal bleeding ? • Any recent change in bowel habit ? • Any new abdominal pain or weight loss ? • A history of colitis ? • Iron deficiency ? – up to 15 % have CRC

  20. One third of CRC cases could be prevented by screening !

  21. Survival depends on early detection !

  22. SCREENING -Screening involves asymptomatic patients ! • Faecal Occult Blood Testing • Flexible Sigmoidoscopy • Colonoscopy • Barium Enema • Virtual Colonoscopy • Detection of DNA mutations & stool tumour markers

  23. Screening • One step – Colonoscopy , select on age. Many individuals will have –ve test ( 4-7 % develop CRC in life time ) Expense and morbidity . Are risks matched by benefit ? • Two Step – Screen with cheap test such as FOBT follow by colonoscopy if +ve - evidence based - colonoscopic resources managed - overcomes initial patient reluctance for invasive test

  24. NBCSP • Pilot from 2002 • About 45% participation rate • Now testing 50, 55, 60 and 65 yr olds • By 2015 include 70 yr olds • 2012-2015 4.8 million Australians eligible • By 2017/18 biennial screening phased in between 50-74 yrs • Expect detect 12 000 new cases /yr and save 300-500 lives

  25. FOBT • Five randomised controlled trials of serial FOBT’s ( more than 250 000 subjects ) - Reduction in CRC mortality of 33 % with annual screening • 21% reduction with biennial screening

  26. FOBT - Types Available • Guaiac – Hemoccult • Haem-derived porphyrin – HemoQuant • Faecal Immunochemical tests – Inform , HemeSelect

  27. Guaiac Tests • Dependent on peroxidase activity of heme molecule which is stable during digestion and therefore not selective for colorectal bleeding • Restriction of heme rich or peroxidase rich foods and some medications . Vit C gives false negatives • Requires testing on three separate occasions • Not suitable for automated testing

  28. Immunochemical Tests - FIT • Detection is based on antibodies specific for human Hb • Not subject to interference by diet or drugs • FIT’s are selective for colorectal bleeding as Hb is degraded by digestion ( do not detect gastric bleeding ) • More sensitive than Guaiac FOBT ‘s with similar specificity : 0.1mg Hb per gram faeces . FIT’s have better performance than guaiac tests • Sampling of toilet bowl water around immersed stool – improved participation • Mass processing by automated reading • FIT tests can be quantified. Sensitivity for cancer may be as high as 68-85 %

  29. Most positive FOBT’s will not be anything serious ! • Do improve detection of asymptomatic CRC • 65 – 90 % Dukes A/B compared to 33-35 % control

  30. FOBT PERFORMANCE • 4 % +ve • 3-5 % CRC • 30 - 45 % Adenomas • 30-40 % CRC missed. • Over 13 yrs – Annual screening : 33% reduction in mortality -Biennial : 20 % reduction

  31. Flexible Sigmoidoscopy • Visualisation of distal bowel where 70 % of cancers occur ( rectum 40% and sigmoid ) • No sedation • Retrospective case controlled studies support reduction in mortality for distal cancers ( 70 % ) but not for proximal lesions • A distal adenoma indicates 2-5 % chance of advanced proximal adenoma • If sigmoidoscopy negative – repeat in 5 yrs

  32. COLONOSCOPY • No RCTs but National Cooperative Polyp Study cohort-1418 pts, 1 or more adenomas removed , followed progressively, CRC incidence 76-90 % lower than expected. Other estimates at least 50 % reduction in risk. • Missed polyps 6-25 %, 6-10 min withdrawal time, good prep • Cost benefit analysis suggests value for colonoscopy at 10 yearly intervals – US guidelines • 1 : 500 post polypectomy haemorrhage • 1 : 1500 chance of bowel perforation

  33. Double Contrast Barium Enema • No randomised trials showing reduction in mortality • Inferior sensitivity to colonoscopy by 5 - 10 % with no prospect for polyp removal nor biopsy

  34. Virtual Colonoscopy • CT or MRI imaging used to develop 2 and 3 dimensional images of colon • Colonic preparation and bowel insufflation with CO2 • No sedation • Minimal risk of bowel perforation , infection or bleeding • Sensitivity good for polyps > 10 mm • No chance of biopsy or polyp removal • No texture or colour detail • High colonoscopy follow up rates – 15 – 25 % • Radiation exposure • No randomised trials showing benefit

  35. Radiation Exposure • Millisieverts • 2-3 mSv/yr • CT – 5- 15mSv • CXR - 0.02mSv • > 100mSv may increase cancer risk • >1000 mSv cumulative increase cancer risk in later years 5/100 develop cancer

  36. Detection of DNA mutations and tumour markers in stool Mutations of genes are associated with malignancy and adenomas Oncogenes ( RAS ) , tumour suppressor genes ( p53 & APC ) , microsatellite instability sequences are known and can be assessed Cells from tumours with the above mutations are shed into the gut and can be detected in stool Screening for a panel of markers is suggested combined with FOBT – promise for future

  37. Key Points • Lifestyle Measures • Identify risk • Screening for asymptomatic patients • 33% reduction in mortality with early detection

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