1. Evidence-base approach in the perioperative management and follow-up strategy for colon cancer Hester YS Cheung Department of surgery Pamela Youde Nethersole Eastern Hospital

2. Common scenario  M/54  No family history of carcinoma of colon  Presented with dizziness  P/E Pale looking, left upper quadrant mass Blood test Hb 4g/dL Liver function test normal Carcinoma of transverse colon

3. Pre-operative assessment CEA Bowel Preparation CT scan Chest X-ray Prophylactic Antibiotic Blood Transfusion Carcinoma of colon

4. Carcinoembryonic antigen (CEA)  Elevated in a variety of conditions  Proximal gastrointestinal cancer, lung and breast cancers, smoking etc.  Proven useful in individuals diagnosed with colorectal cancer Recommended before resection of colorectal cancer Level of evidence Class II A Graham RA, Ann Surg 1998 Wiratkapun S. Dis Colon Rectum 2001

5. Pre-operative CEA  Returning to normal after operation is associated with complete tumor resection  Persistently elevated values indicate the presence of visible or occult residual disease Lavin PT. Cancer 1981 Steele G. Ann Surg 1982

6. Pre-operative CEA  An independent prognostic indicator of poor outcome  Predictive of poor survival  shorter disease-free survival  Metastases in 37% patients with elevated preoperative CEA vs. 7.5% in patients with normal CEA Wiratkapun S. Dis Colon Rectum 2001 Harrison LE. J Am Coll Surg 1997

7. Chest x-rays  Overall pre-operative assessment  Evaluate lungs for metastatic disease Routine pre-operative chest x-ray is acceptable Level of evidence Class III C The Standards Practice Task Force Dis Colon Rectum 2004 Low cost Low yield for metastatic disease

8. Computed tomography (CT scan)  Evaluate local extension of tumor, regional lymphadenopathy and the presence of hepatic metastases  Accuracy of CT scan McAndrew MR. Am Surg 1999 Hundt W. Eur Radiol 1999 Ward J. Radiology 1999 Sensitivity Limited data Local extensionLimited data 19-67% Metastatic lymphadenopathy19-67% 90-95% Liver metastases >1cm90-95%

9. Computed tomography (CT scan)  No impact on the decision to operate  Not affect the operative approach  Information readily obtained at the time of surgery Routine pre-operative CT scan is optional Level of evidence Class II B The Standards Practice Task Force Dis Colon Rectum 2004

10. Computed tomography (CT scan)  Suspicion of invasion of adjacent organs  Palpable mass  Unexplained biochemical abnormalities  Nearly obstructing cancer Used in selected patients for pre-operative planning The Standards Practice Task Force Dis Colon Rectum 2004

11. Peri-operative blood transfusion  Established immunosuppressive effect  Higher incidence of infection  Wound infection  Intra-abdominal sepsis  Pneumonia  Greater risk of cancer recurrence  Decreased survival Is it harmful? Jensen LS. Br J Surg 1992 Van Twuyver E. N Eng J med 1991

12. Perioperative blood transfusion STUDIESPatients 5-year Survival Disease-free Survival Cancer Recurrence Local Recurrence Post-operative Infection Van de Watering LM 2001697↓↓↑ SAKK1997450↓ Hobiers JG 1997697↑ Dose response RR 1.6 (1-3U) RR 3.6 (>3U) Busch OR 1994420↑ Heiss MM 1994120↓↑ Randomized controlled trials

13. Perioperative blood transfusion STUDIESPapersSurvival Cancer Recurrence Poor Prognostic Factor Post-operative Infection Amato AC Dis Colon Rectum 1998 32↑ Odds ratio 1.68 √ McAlister FA Br J Surg 1998 8NodifferenceNodifference Vamvakas EC Transfusion 1995 60 Discrepancies explained by study design and confounding factors Fernadez L Rev Esp Enferm Dig 1992 Nodifference Meta-analyses

14. Perioperative blood transfusion  Strongly questioned whether there is a true causal effect  Factors in patients requiring transfusion might be the cause for increased recurrence  Extent of resection  Location of tumor  Experience of surgeon Meta-analyses The Standards Practice Task Force Dis Colon Rectum 2004

15. Perioperative blood transfusion Simon TL. Arch Pathol Lab Med 1998 Red Blood Cell Administration Practice Guideline Development Task Force of the College of American Pathologists Peri-operative transfusion Asymptomatic anaemia and haemoglobin ≤ 7 g/dL may need to be transfused if: A. Scheduled surgery is expected to produce significant blood loss B. Risks associated with general anaesthesia are high

16. Pre-operative blood transfusion Blood transfusion should be based on physiological need e.g. starting haemoglobin, physiological status and extent of intra-operative blood loss Level of evidence Class III C Vignali A. Eur J Surg 1995 Houbiers JG. Lancet 1994 The Standards Practice Task Force Dis Colon Rectum 2004

17. Mechanical bowel preparation YearAnastomostic LeakageWound Infection PrepNo PrepPrepNo Prep Brownson et al 19928/671/675/867/93 Burke et al 19943/824/874/823/87 Santos et al 19947/724/7717/729/77 Fillmann et al 19952/301/30 2/30 Miettinen et al 20005/1383/1295/1383/129 Tabusso et al 20025/240/232/240/23 Zomera et al 20037/1874/19312/18711/193 Bucher et al 20034/471/464/471/46 Fa-Si-Oen et al 20037/1256/1259/1257/125  No definite benefit for pre-operative mechanical preparation of bowel  9 RCTs showed no decrease in  Infection rate  Leakage rate  Mortality rate

18. Mechanical bowel preparation  Ease of handling prepared colon  Proven safety for colon cleansing  Low cost Mechanical bowel preparation is nearly universally used in elective surgery Level of evidence Class II A The Standards Practice Task Force Dis Colon Rectum 2004

19. Prophylactic antibiotics  Proven effectiveness in decreasing  Infective complications  Mortality  Cost of hospitalization after colonic resection  Parenteral antibiotic regimen  Given before the start of operation  Need not be continued longer than 24 hours post-operatively  Single dose of Cefotaxime and Metronidazole is as effective as 3 doses Baum ML. N Eng J Med 1981 Stone HH. Ann Surg 1976, Polk HC. Surgery 1969 Stone HH. Ann Surg 1979 Rowe-Jones DC. BMJ 1990

20. Prophylactic antibiotics Prophylactic antibiotics are recommended for patients undergoing colon resection Level of evidence Class I A The Standards Practice Task Force Dis Colon Rectum 2004

21. Post-operative surveillance Follow-up Colonoscopy Imaging Carcinoma of colon Laboratory Tests

22. Intensive follow-up  85% recurrences diagnosed within the first 3 years after resection of primary tumor Sargent DJ. J Clin Oncol 2004 FrequencyDuration Desch et al. J Clin Oncol 2005 American Society of Clinical Oncology Practice Guideline Follow-up strategy First 3 years First 3 yearsEvery 3-6 months 4th and 5th year 4th and 5th yearEvery 6 months After 5th year After 5th year Discretion of surgeon

23. Post-operative follow-up  Intensive follow-up  3 high-quality meta-analyses  20-30% reduction in risk of death from all causes for patients who received more intensive follow-up

24. Intensive follow-up  Earlier documentation of recurrences  Increase in operability of recurrent disease  Patient health-related quality of life (HRQL)  Limited data  No difference in cohort studies Desch et al. J Clin Oncol 2005 Stiggelbout AM. Br J Cancer 1997 Kjeldsen BJ. Scand J Gastroenterol 1999

25. Laboratory tests  Haemoglobin  1% recurrence  No survival benefit  Liver function test  < 10% recurrence  Resectable recurrence: 2-3 patients per 1000 followed-up  Faecal occult blood test  10-30% recurrence/metachronous lesions  Resectable recurrence: 0-9 per 1000 patients followed-up Kjelden BJ. Br J Surg 1997 Goldberg RM. Ann Intern med 1998 Peethambaram P. Oncology 1997 Graffner H. J Surg Oncol 1985 Jahn H. Dis Colon Rectum 1992 Not recommended for routine blood test Level of evidence Class II A

26. Laboratory tests  Carcinoembryonic antigen (CEA)  Positive predictive value of 70-80% for recurrent disease if level > 5ng/ml  First indicator of recurrence  First abnormal test in 38-66% recurrences  Lead-time 4-6 months  Survival advantage not demonstrated  False positive rate 7-16% Pros Cons McCall JL. Dis Colon Rectum 1994, Moertel CG. JAMA 1993 Ohlsson B. Dis Colon Rectum 1995 McCall JL. Dis Colon Rectum 1994 The Standards Practice Task Force Dis Colon Rectum 2004 Used as a part of follow-up Level of evidence Class II B

27. Laboratory tests  Carcinoembryonic antigen (CEA) American Society of Clinical Oncology Practice Guideline Post-operative CEA testing Every 3 months in patients with Stage II/III disease for at least 3 years Candidate for surgery or systemic therapy

28. Imaging STUDIESPatients Asymptomatic Hepatic Metastases Hepatic Resection Rate Survival Chau I J Clin Oncol 2004 530 No difference ↑↑ Schoemaker D Gastroenterology 1998 325↑60% No difference  Computed tomography (CT scan)  2 RCTs addressed the impact of CT scan on survival  25% lower mortality Desch et al. J Clin Oncol 2005

29. Imaging American Society of Clinical Oncology Practice Guideline CT in colon cancer surveillance (2005) Annual CT for 3 years after primary therapy For patients with Higher risk of recurrence Candidates for curative-intent surgery

30. Colonoscopy  Identify metachronous cancers and polyps American Society of Clinical Oncology Practice Guideline Endoscopic surveillance Following surgery Following surgeryAt 3 years if normal, then every 5 years High-risk genetic syndromes

31. In conclusions  CEA is recommended  CXR  CT abdomen is optional  Mechanical bowel preparation is still a common practice  Prophylactic antibiotics is recommended  Blood transfusion based on physiological need high risk patients & candidates for curative surgery or systemic treatment  Intensive follow up  CEA  Annual CT scan  Surveillance colonoscopy at 3 years and then 5 years Pre-operativePost -operative

32. Thank you

33. Level of evidence