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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. Common scenario. M/54 No family history of carcinoma of colon Presented with dizziness
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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
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
Pre-operative assessment CT scan Chest X-ray CEA Carcinoma of colon Blood Transfusion Bowel Preparation Prophylactic Antibiotic
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
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
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 Harrison LE. J Am Coll Surg 1997 Wiratkapun S. Dis Colon Rectum 2001
Chest x-rays • Overall pre-operative assessment • Evaluate lungs for metastatic disease Low yield for metastatic disease Low cost Routine pre-operative chest x-ray is acceptable Level of evidence Class III C The Standards Practice Task Force Dis Colon Rectum 2004
Computed tomography (CT scan) • Evaluate local extension of tumor, regional lymphadenopathy and the presence of hepatic metastases • Accuracy of CT scan Sensitivity Local extension Limited data Metastatic lymphadenopathy 19-67% Liver metastases >1cm 90-95% McAndrew MR. Am Surg 1999 Hundt W. Eur Radiol 1999 Ward J. Radiology 1999
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
Computed tomography (CT scan) Used in selected patients for pre-operative planning • Suspicion of invasion of adjacent organs • Palpable mass • Unexplained biochemical abnormalities • Nearly obstructing cancer The Standards Practice Task Force Dis Colon Rectum 2004
Peri-operative blood transfusion Is it harmful? • Established immunosuppressive effect • Higher incidence of infection • Wound infection • Intra-abdominal sepsis • Pneumonia • Greater risk of cancer recurrence • Decreased survival Jensen LS. Br J Surg 1992 Van Twuyver E. N Eng J med 1991
Perioperative blood transfusion Randomized controlled trials
Perioperative blood transfusion Meta-analyses
Perioperative blood transfusion Meta-analyses • 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 The Standards Practice Task Force Dis Colon Rectum 2004
Perioperative blood transfusion 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 Simon TL. Arch Pathol Lab Med 1998
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
Mechanical bowel preparation • No definite benefit for pre-operative mechanical preparation of bowel • 9 RCTs showed no decrease in • Infection rate • Leakage rate • Mortality rate
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
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
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
Post-operative surveillance Laboratory Tests Imaging Carcinoma of colon Follow-up Colonoscopy
Intensive follow-up Frequency Duration • 85% recurrences diagnosed within the first 3 years after resection of primary tumor Sargent DJ. J Clin Oncol 2004 American Society of Clinical Oncology Practice Guideline Follow-up strategy First 3 years Every 3-6 months 4th and 5th year Every 6 months After 5th year Discretion of surgeon Desch et al. J Clin Oncol 2005
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
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
Laboratory tests Kjelden BJ. Br J Surg 1997 • 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 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
Laboratory tests Pros McCall JL. Dis Colon Rectum 1994, Moertel CG. JAMA 1993 • 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% Ohlsson B. Dis Colon Rectum 1995 McCall JL. Dis Colon Rectum 1994 Cons Used as a part of follow-up Level of evidence Class II B The Standards Practice Task Force Dis Colon Rectum 2004
Laboratory tests • 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 • Carcinoembryonic antigen (CEA)
Imaging • Computed tomography (CT scan) • 2 RCTs addressed the impact of CT scan on survival • 25% lower mortality Desch et al. J Clin Oncol 2005
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
Colonoscopy • Identify metachronous cancers and polyps American Society of Clinical Oncology Practice Guideline Endoscopic surveillance Following surgery At 3 years if normal, then every 5 years High-risk genetic syndromes
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 In conclusions Pre-operative Post -operative