1. Colonoscopy – Ready to be Replaced as a Screening Tool? Vivien Wong North District Hospital January 16 th, 2010 Joint Hospital Surgical Grand Round

2. Colorectal Cancer High incidence among both male and female in Hong Kong High incidence among both male and female in Hong Kong –2 nd most commonly diagnosed cancer  4000 cases per year –2 nd most common cause for cancer death  1700 cases per year Hong Kong Cancer Registry 2007 Well-established treatment Well-established treatment Known possible malignant transformation of benign adenomatous polyps Known possible malignant transformation of benign adenomatous polyps –Removal of benign polyps can prevent development into invasive carcinoma

3. Colonoscopy Investigation of choice Investigation of choice Invasive Invasive Risk of perforation Risk of perforation Discomfort Discomfort Sedation/GA Sedation/GA Any non-invasive method to replace colonoscopy for screening? Any non-invasive method to replace colonoscopy for screening?

4. Barium enema The conventional alternative in patients not suitable or unwilling to perform colonoscopy The conventional alternative in patients not suitable or unwilling to perform colonoscopy Efficacy significantly lower compared to colonoscopy Efficacy significantly lower compared to colonoscopy Sosna et al. Critical Analysis of the Performance of Double-Contrast Barium Enema for Detecting Colorectal Polyps 6 mm in the Era of CT Colonography. Am J Roentgenol, Feb 2008; 190: 374 - 385. Polyps ≥ 10mm Polyps 6-9 mm Sensitivity70%45% Specificity85%

5. New technology New technology  CT Colonography  Capsule endoscopy

6. CT Colonography

7. CT Colonography (CTC) Introduced since mid-1990s Introduced since mid-1990s Uses computed tomography to perform an imaging evaluation of the colon Uses computed tomography to perform an imaging evaluation of the colon Requires distension of large bowel for viewing of intraluminal lesions Requires distension of large bowel for viewing of intraluminal lesions a.k.a. “Virtual Colonoscopy”

8. Recent screening guidelines Recent screening guidelines –The ACS guideline 2010  CTC is listed as one of the option of CRC screening in average-risk population over age of 50 –The ACG guideline 2009  CTC every 5 years replaced barium enema as the alternative colorectal cancer prevention test

9. Advantages: Non-invasive Non-invasive Assessment of extra-colonic pathology Assessment of extra-colonic pathologyConcerns: Sensitivity and Specificity Sensitivity and Specificity Safety issue Safety issue –Bowel preparation –Colonic distention –Radiation

10. Sensitivity and Specificity Initial small trials involved polyp-rich cohorts and focused largely on technique development Initial small trials involved polyp-rich cohorts and focused largely on technique development Subsequent larger trials 2003-2005 Subsequent larger trials 2003-2005 No. of patients Polyps ≥ 6mm SensitivitySpecificity Cotton et al 2004 60039%90.5% Rockey et al 61451%-- Johnson et al 70357%95%

11. New techniques developed New techniques developed –Stool tagging –3D-reconstruction views –Multidetector row CT scanners No. of Patients Polyps ≥ 6mm Adenoma ≥ 10mm SensitivitySpecificitySensitivitySpecificity Pickardt et al 123389%94%89% Stool tagging Stool tagging 3D polyp detection 3D polyp detection ACRIN 6664 >2500 in 15 centers --90%86% Stool tagging Stool tagging Automated CO2 delivery Automated CO2 delivery ≥16 slice multidetector row CT ≥16 slice multidetector row CT 2D and 3D polyp detection 2D and 3D polyp detection Munich300--92% 64 slice multidetector CT 64 slice multidetector CT 3D polyp detection 3D polyp detection Mayo Clinic 452--95% 3D polyp detection 3D polyp detection Regge et al 937 in 20 centers 85%88%----

12. The Recommended Specifications Bowel preparation PEG or phosphosoda PEG or phosphosoda Stool & fluid tagging Not mandatory but recommended and validated Not mandatory but recommended and validated Bowel distension Scanning in two positions Scanning in two positions Automatic insufflation recommended Automatic insufflation recommended Acquisition parameters & radiation dose Multidetector CT ≥ 4 slice Multidetector CT ≥ 4 slice Slice thickness ≤ 3mm Slice thickness ≤ 3mm Reconstruction level ≤ 2mm Reconstruction level ≤ 2mm Low radiation dose, ≤ 50% of the diagnostic reference level for routine abdominopelvic CT Low radiation dose, ≤ 50% of the diagnostic reference level for routine abdominopelvic CT Data interpretation To ensure adequate bowel distension: 2D view To ensure adequate bowel distension: 2D view Polyp detection: Primary 2D or 3D search Polyp detection: Primary 2D or 3D search Polyp characterization: 2D multiplanar or 3D images, data from both positions, and multiple window settings Polyp characterization: 2D multiplanar or 3D images, data from both positions, and multiple window settings McFarland et al. ACR Colon Cancer Committee White Paper: Status of CT Colonography 2009. J Am Coll Radiology 2009;6:756-772

13. Capsule Endoscopy of the Colon

14. Capsule endoscopy of the colon Cleared for marketing in European Union since 2006 Cleared for marketing in European Union since 2006 Uses an ingestible capsule with cameras to acquire video images of the colonic mucosa as it goes through the bowel Uses an ingestible capsule with cameras to acquire video images of the colonic mucosa as it goes through the bowel PillCam Colon (Given Imaging, Yoqneam, Israel)

15. Capsule endoscopy of the colon Cleared for marketing in European Union since 2006 Cleared for marketing in European Union since 2006 Uses an ingestible capsule with cameras to acquire video images of the colonic mucosa as it goes through the bowel Uses an ingestible capsule with cameras to acquire video images of the colonic mucosa as it goes through the bowel PillCam Colon (Given Imaging, Yoqneam, Israel) 31mm x 11mm Two cameras at each end covering 156° Acquires pictures at rate of 4 fps Esophagus & Stomach Small Intestine Terminal ileum & Colon Sleep mode Reactivation after 2 hours

16. Bowel preparation Bowel preparation –Polyethylene glycol solution –Sodium phosphate –Domperidone –Bisacodyl rectal suppository Data recording Data recording –Data transmitted from capsule to a data recorder connected to the patient during the procedure Analysis Analysis –Given Imaging RAPID workstation

17. Non-invasive Non-invasive Less discomfort Less discomfort Sedation-free Sedation-free Away from doctor’s office Away from doctor’s office –Less disruption to patient’s routine How well does it do? How well does it do?

18. Pubmed and MEDLINE search: Pubmed and MEDLINE search: –“Pillcam colon”, “capsule colon endoscopy” Six prospective trials Six prospective trials One cost-effectiveness study One cost-effectiveness study One safety study with pacemakers One safety study with pacemakers Case reports Case reports

19. Venue of study Patients recruited (analyzed) Age of patients (mean) Any polyps Polyp ≥ 6mm Sensitivity (95% CI) Specificity (95% CI) Sensitivity (95% CI) Specificity (95% CI) Eliakim et al 2006 Israel 91 (84) 26-75 (57) 56% (39-72) 69% (56-82) 50% (26-75) 83% (73-91) Schoofs et al 2006 Belgium 41 (36) 26-75 (56) 76%64%60%73% Gay et al 2009 France 128 (126) n/a (55) 76%76%69%n/a Sieg et al 2009 Germany 38 (36) 23-73 (56) 55%96%n/an/a Gossum et al 2009 8 European centres 332 (320) 22-84 (58) 72% (68-75) 78% (71-84) 64% (59-72) 84% (81-87) Comparative Studies: Pillcam Colon vs Colonoscopy

20. Venue of study Patients recruited (analyzed) Age of patients (mean) Any polyps Polyp ≥ 6mm Sensitivity (95% CI) Specificity (95% CI) Sensitivity (95% CI) Specificity (95% CI) Eliakim et al 2006 Israel 91 (84) 26-75 (57) 56% (39-72) 69% (56-82) 50% (26-75) 83% (73-91) Schoofs et al 2006 Belgium 41 (36) 26-75 (56) 76%64%60%73% Gay et al 2009 France 128 (126) n/a (55) 76%76%69%n/a Sieg et al 2009 Germany 38 (36) 23-73 (56) 55%96%n/an/a Gossum et al 2009 8 European centres 332 (320) 22-84 (58) 72% (68-75) 78% (71-84) 64% (59-72) 84% (81-87) Comparative Studies vs Colonoscopy 11.6mm x 31.5mm 11.6mm x 31.5mm Increased angle of view to 172° Increased angle of view to 172° Adjusts frame rate automatically Adjusts frame rate automatically –35 fps while in motion –4 fps while stationary Measuring tool in the analysis software for polyp size Measuring tool in the analysis software for polyp size

21. Venue of study 5 Israeli centres Patients recruited 104 Patients analyzed 98 Age of patients (mean) 18-57 (50) Polyps ≥ 6mm Sensitivity Sensitivity89 Specificity Specificity76 Polyps ≥ 10mm Sensitivity Sensitivity88 Specificity Specificity89 Eliakim et al. Prospective mulitcenter performance evaluation of the second-generation colon capsule compared with colonoscopy. Endoscopy 2009;41:1026-1031. Comparative Study: Pillcam Colon 2 vs Colonoscopy

22. Safety Safety –No complication from the capsule in all the six prospective trials –Incompliance mainly due to anxiety (and hence inability to swallow the capsule) –Capsules were proven safe to use in patients with implantable cardioverter-defibrillators Bandorski et al. Do endoscopy capsules interfere with implantable cardioverter-defibrillators? Endoscopy 2009;41:457-461

23. Conclusion Colorectal cancer is a significant disease suitable for population screening Colorectal cancer is a significant disease suitable for population screening Colonoscopy is the screening tool of choice at the moment in suitable patients Colonoscopy is the screening tool of choice at the moment in suitable patients Non-invasive screening tool is under development in hope to replace the invasive colonoscopy Non-invasive screening tool is under development in hope to replace the invasive colonoscopy CT colonography is now accepted as a primary screening tool in the average-risk population in America CT colonography is now accepted as a primary screening tool in the average-risk population in America Efficacy of colon capsule endoscopy is yet to be proven Efficacy of colon capsule endoscopy is yet to be proven

24. In our locality…? HospitalColonoscopyCTCCapsule A$14820-$27840$5800$17000-$20000 B$7300$5000-$7600n/a Cn/a$4500n/a No official colorectal cancer screening programme launched yet No official colorectal cancer screening programme launched yet Which method to adopt as the primary investigation to achieve best efficacy is still yet to be defined Which method to adopt as the primary investigation to achieve best efficacy is still yet to be defined

25. Thank you Thank you

26. Screening Routine examination of asymptomatic population of a disease Routine examination of asymptomatic population of a disease Criteria Criteria 1. Important health issue 2. Acceptable treatment a/v 3. Facilities for Dx and Rx a/v 4. Condition can be recognised at early/ latent stage 5. Suitable test for screening a/v 6. Screening test acceptable to population 7. Natural history of disease well understood 8. Agreed policy on whom to treat 9. Cost of dx and rx economically balanced 10. Case finding should be continued