Medicine For People!

October 2010

Colon Cancer Screening Part III – A Safe and Sane Approach

Over our lifetimes, we have about a 6 percent chance of developing colon cancer. Wait for symptoms, and only about half of us will last five years. Find it early, and it's gone forever.

Our previous newsletters outlined the developmental timeline of an individual colon cancer and reviewed the current media-hyped screening tool, colonoscopy with polyp removal. I believe performing colonoscopies on everyone is overkill. We don't have every bump or barnacle removed from our skin; there's no point and it's costly. Similarly with the colon lining, our goal is not to eliminate every growth, every polyp; it is to detect colon cancer at an early stage so it can be cured, exactly as we do with skin growths.

This month you'll learn about a new test, the immunochemical fecal occult blood test, the iFOBT, a second-generation test for blood hidden in the stool. Used annually as a preliminary tool, this test can discover who actually needs a colonoscopy and eliminate the need for all of us to get scoped once every ten years. System-wide, it could reduce the number of colonoscopies required to discover and treat colon cancer.

IFOBT: Immunochemical fecal occult blood test

The iFOBT measures microscopic amounts of blood in the stool. You may remember the old card test, called the FOBT, or guaiac test. People had to avoid meat and vitamin C (both of these would turn the test falsely positive), then smear poop on a card for three days. The test was sometimes difficult to read, too often falsely positive, too often falsely negative.1 Getting people to collect the sample and return the cards took some doing as well.

The iFOBT accurately measures human blood in the stool. People with no polyps or with benign polyps pass little or no blood in the stool, which this test accurately determines. You can see how this works.

While the guaiac test did reduce death from colon cancer by about 15 to 20 percent,2 the iFOBT, done annually, picks up about 80 percent of colon cancer. Run the test three years running, as will happen by the age of 53 assuming we start screening at age 50, and that number rises to 94 percent.3 4 5 6 For those who test positive on the iFOBT, the next step is a colonoscopy to get a better look at the situation.

Two-Stage Screening: Colonoscopy only when indicated

Most developed countries7 8 9 use this two-step colon cancer screening program, offering all patients of age an iFOBT followed by colonoscopy for those who test positive.

The iFOBT accurately measures human blood without regard for vitamin C or meat. It measures the concentration of blood in the stool. Benign polyps cause lower concentrations of blood, while pre-malignant polyps result in larger concentrations. The lab sets the cut-off for positivity at a level to distinguish between the two.

This is our strategy: rather than firing off our big gun (colonoscopy) every ten years no matter what, we take a look every year. We watch 'til we see the whites of their eyes as it were, wait for some blood to show up on our annual iFOBT test; and then take aim. We do not worry about every polyp. Our guns don't matter at that distance, and the polyp may go away on its own. But the closer danger comes, the more likely our iFOBT is to be positive, and once the polyp shows malignant characteristics, the iFOBT has a 95 percent chance of putting the finger on it, a similar percentage to the performance of colonoscopy.10 Studies of iFOBT show that this approach finds cancer earlier11 than the old FOBT test. See appendix for a risk model that supports this approach.

In summary, wait ten years between colonoscopies, and a cancer can grow. Run an iFOBT every year and you have a good chance to catching it as it crosses the line between the common benign polyp and localized microscopic cancer.

If you look, you will find voices12 dissenting from mine. I haven't come to my point of view lightly. I've dissected their scholarly papers and their arguments. As more and more medical authorities are noting, every organization exists to promote the interests of its members, to puff the value of its product or service. Just this month in the New England Journal an editorialist writing about mammography adds that medicine is no different13, noting

"We must acknowledge that just as in any other profession or industry, self-interest is unavoidably at work in health care."14

Today we doctors are rolling back our enthusiasm about mammography under age 50. Shortly, I believe, we are going to roll back our enthusiasm about colonoscopy for all. We need to reserve care, including colonoscopy, for those for whom it provides a clear and certain benefit.

Ask those who don't profit from colonoscopy, the U.S. Preventive Services Task Force (USPSTF), and they recommend EITHER colonoscopy every ten years OR an iFOBT every year. That's because, like me, they believe that we should be as comprehensive in our screening for colon cancer as we are for breast and cervical cancer, and our "colonoscopy for all" program is getting in the way. As one cancer specialist pleads, "A less invasive starting point, such as the iFOBT, might help us achieve that goal".15 Supporters of colonoscopy for all recommend an every-ten-year screen, even though analysis shows that most of the benefit of colonoscopy comes from the initial examination and removal of polyps16, with an average of three months additional lifetime added by repeat procedures.17 On the other hand, as we showed in last month's newsletter, colonoscopies can have serious side effects, including death. If we can avoid 20 million unnecessary colonoscopies, we can avoid 1000 unnecessary deaths from the procedure.

To summarize–

A Good Cancer Screening Test Must...

  • Be acceptable to the majority of people.
  • Find an illness at a stage when intervention prolongs health and wellness
  • Be affordable

IFOBT, followed by colonoscopy when positive, meets these criteria.

Recommendations

If you belong to a family diagnosed with a specific genetic predisposition to colon cancer, you are in a special category; follow the advice of your doctor.

If you do not have any risk factors for colon cancer, remember that 80 percent of the people diagnosed with colon cancer last year had no risk factors either. Get an IFOBT every year after age 50 if male, age 55 if female18. After the age of 75, many doctors discontinue colon cancer screening as the "lead time between the detection and treatment of colorectal neoplasia and a mortality benefit is substantial, and competing causes of mortality make it progressively less likely that this benefit will be realized with advancing age."19

Even promoters of colonoscopy admit that just sticking with any of the major screening schemes "will be more important in life-years gained than will the particular regimen selected."20 Since the advent of the iFOBT, more and more doctors21 support this two-stage program.

How to do the test

There are several varieties of the new immunochemical test, abbreviated Ifobt, of which some are better than others. I recommend Quidel Corporation's QuickVue,22 the test provided by Labcorp in Seattle.

Collection of the sample is easy. In our office, the nurse gives you instructions on what to do at home with the collection kit.

Take an aspirin or another NSAID (ibuprofen, etc) once a day for three days before the test if you wish to increase the sensitivity of the test. This will make any pre-cancerous lesion more likely to bleed and turn the test positive.23 This does not seem to increase the false positive rate.

If you have noticed bright red blood on the toilet paper, talk to your doctor before you undertake an ifobt. Do not follow preceding advice about aspirin. Do not cancel or long delay your colon cancer screening. Assuming the blood is all from the hemorrhoids can be a fatal mistake.24

Return the sample the day after you collect it.

What Does the Future Hold?

The iFOBT test costs $63. As it becomes more popular the price will come down. Pre-test risk scoring questionnaires will augment the predictive value of the iFOBT.25 Right now about 75 colonoscopies are required to find one colon cancer. If you pre-screen with Ifobt, you only have to do twenty-one.26 That number will only improve. We'll be able to increase participation in our screening program, be less likely to cause adverse effects from unnecessary colonoscopies, and will detect and prevent more colon cancer at a lower cost that which currently obtains. 27

Resources

Supplementary information for this newsletter

For more information about cancer screening, read Should I be Tested for Cancer? By Gilbert Welch, MD

Endnotes

1 ifobt vs gfobt.pdf

van Rossum LG, van Rijn AF, Laheij RJ, et al.: Random comparison of guaiac and immunochemical fecal occult blood tests for colorectal cancer in a screening population. Gastroenterology 2008, 135:82–90.

ABS: The number-to-scope to find 1 cancer was comparable between the tests. However, participation and detection rates for advanced adenomas and cancer were significantly higher for IFOBT. G-FOBT significantly underestimates the prevalence of advanced adenomas and cancer in the screening population compared with I-FOBT.

This study compared FIT and g-FOBT in a screening population with colonoscopies as follow-up. Participation and detection rates for cancers and advanced adenomas were higher in the FIT group. The numbers needed to screen to fi nd cancer +/- advanced adenoma were lower with FIT. This study shows a higher patient acceptance of FIT (possibly because of the simpler regimen) and a lower colonoscopy requirement, which may offset its higher unit cost.

2 "The published RCTs using the standard GFOBT, Hemoccult, have observed modest population mortality reductions (from colorectal cancer) of 14–21% when analyzed on an intention-to-screen basis" Digestion 2007;76:26–33

3 Levi Z,Rozen P,Hazazi R,Vilkin A,Waked A,Maoz E,Birkenfeld S,Leshno M,Niv Y. "A quantitative immunochemical fecal occult blood test for colorectal neoplasia." Annals of Internal Medicine. 2007 Feb 20;146:244-55. (Issue number 4) Copy in office. topics\GI\Colon Cancer screen\iFOBT 1.pdf topics\GI\iFOBT.pdf Research reported by Rabin Medical Center, Beilinson Hospital, Petach Tikva, Israel.. =21946= Nomogram takes pretest probability and quantitative iFOBT to arrive at posttest probability. = Conclusion: Quantitative immunochemical FOBT has good sensitivity and specificity for detection of clinically significant neoplasia. Test performance in screening average-risk populations is not known. = Author's abstract: BACKGROUND: Guaiac-based fecal occult blood tests (FOBTs) for colorectal cancer screening are not specific for human hemoglobin and have low sensitivity. Automated-development, immunochemical FOBT is quality-controlled, is specific for human hemoglobin, and does not require diet restriction. OBJECTIVES: To measure the sensitivity and specificity of quantitative immunochemical fecal hemoglobin measurements for detection of cancer and advanced adenoma in patients undergoing colonoscopy, to determine fecal hemoglobin thresholds that give the highest posttest probability for neoplasia, and to determine the number of immunochemical FOBTs needed. DESIGN: Prospective, cross-sectional study. SETTING: Ambulatory endoscopy services of the main health medical organization in Tel Aviv, Israel. PARTICIPANTS: 1000 consecutive ambulatory patients--some asymptomatic but at increased risk for colorectal neoplasia and some symptomatic--who were undergoing elective colonoscopy and volunteered to prepare immunochemical FOBTs. INTERVENTION: The hemoglobin content of 3 bowel movements was measured, and the highest value was compared with colonoscopy findings. MEASUREMENTS: Sensitivity, specificity, predictive values, likelihood ratios, and 95% CIs of fecal hemoglobin measurements for clinically significant neoplasia, their relationship to the amount of fecal hemoglobin measured, and the number of immunochemical FOBTs performed. RESULTS: Colonoscopy identified clinically significant neoplasia in 91 patients (cancer in 17 patients and advanced adenomas in 74 patients). Using 3 immunochemical FOBTs and a hemoglobin threshold of 75 ng/mL of buffer, sensitivity and specificity were 94.1% (95% CI, 82.9% to 100.0%) and 87.5% (CI, 85.4% to 89.6%), respectively, for cancer and 67% (CI, 57.4% to 76.7%) and 91.4% (CI, 89.6% to 93.2%), respectively, for any clinically significant neoplasia. LIMITATIONS: The fecal sampling method is standardized, but the sample size depends on fecal consistency. Some patients were tested while discontinuing aspirin and anticoagulant therapies. Study patients were at increased risk, and results might not apply to average-risk populations.

4 CRC screen guideline.pdf

Levin B, Lieberman DA, McFarland B, et al. Screening and surveillance for early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. Gastroenterology 2008;134:1570-95. ifobt not rec per nej

Goal is CRC prevention, not just detection, and cs finds at least half of prevalent or incident CRC.

The sensitivity for cancer with 3 FIT samples with a hemoglobin threshold set at 75 ng/mL was 94.1%. Specificity for cancer was 87.5%. Allison and colleagues recently published results of a comparison of a sensitive gFOBT (Hemoccult SENSA) with an FIT (Hemoccult ICT) for cancer and advanced adenomas in the distal colon in nearly 6000 average-risk subjects who had undergone FSIG. Both tests showed superior sensitivity for cancer compared with the single-test performance of an unrehydrated gFOBT. The sensitivity for CRC of the FIT and the sensitive gFOBT was 81.8% and 64.3%, respectively.

Annual screening with FIT that have been shown in the published peer-reviewed literature to detect a majority of prevalent CRC in an asymptomatic population at the time of testing is an acceptable option for colorectal screening in average-risk adults aged 50 years and older. Page 1577

CSPY has several limitations. It requires one or more days of dietary preparation and bowel cleansing, usually a day dedicated to the examination, and because of sedation, a chaperone is needed for transportation. It is an invasive procedure, and surveys indicate that a significant percentage of adults prefer other noninvasive options for CRC screening.71,115,116 Effective performance of the procedure is dependent on thorough bowel preparation, which is often perceived as the most unpleasant part of the CSPY process by those who have undergone the test. Limitations with regard to detection of neoplasia have been previously discussed, and the fact that CSPY is operator skill dependent is another significant limitation. Patients are generally poorly informed about the problem of variable performance of the procedure and are unaware of the skill level of their endoscopists. Formal quality assurance programs do not exist, and the current reimbursement system for CSPY does not reward careful examination but tends to reward rapidly performed examinations and repeated examinations at unnecessarily short intervals.117 Polypectomy is sometimes ineffective in eradicating polyps, a factor that has been implicated as the cause of up to 25% of interval cancers.118,119 Finally, CSPY is not an infallible "gold standard." Controlled studies have shown the CSPY miss rate for large adenomas (10 mm) to be 6% to 12%.120,121 The reported CSPY miss rate for cancer is about 5% pg 1582

5 iFOBT 1.pdf

A Quantitative Immunochemical Fecal Occult Blood Test for Colorectal Neoplasia

Background: Guaiac-based fecal occult blood tests (FOBTs) for colorectal cancer screening are not specific for human hemoglobin and have low sensitivity. Automated-development, immunochemical FOBT is quality-controlled, is specific for human hemoglobin, and does not require diet restriction. Objectives: To measure the sensitivity and specificity of quantitative immunochemical fecal hemoglobin measurements for detection of cancer and advanced adenoma in patients undergoing colonoscopy, to determine fecal hemoglobin thresholds that give the highest posttest probability for neoplasia, and to determine the number of immunochemical FOBTs needed. Design: Prospective, cross-sectional study. Setting: Ambulatory endoscopy services of the main health medical organization in Tel Aviv, Israel. Participants: 1000 consecutive ambulatory patients—some asymptomatic but at increased risk for colorectal neoplasia and some symptomatic—who were undergoing elective colonoscopy and volunteered to prepare immunochemical FOBTs. Intervention: The hemoglobin content of 3 bowel movements was measured, and the highest value was compared with colonoscopy findings. Measurements: Sensitivity, specificity, predictive values, likelihood ratios, and 95% CIs of fecal hemoglobin measurements for clinically significant neoplasia, their relationship to the amount of fecal hemoglobin measured, and the number of immunochemical FOBTs performed. Results: Colonoscopy identified clinically significant neoplasia in 91 patients (cancer in 17 patients and advanced adenomas in 74 patients). Using 3 immunochemical FOBTs and a hemoglobin threshold of 75 ng/mL of buffer, sensitivity and specificity were 94.1% (95% CI, 82.9% to 100.0%) and 87.5% (CI, 85.4% to 89.6%), respectively, for cancer and 67% (CI, 57.4% to 76.7%) and 91.4% (CI, 89.6% to 93.2%), respectively, for any clinically significant neoplasia. Limitations: The fecal sampling method is standardized, but the sample size depends on fecal consistency. Some patients were tested while discontinuing aspirin and anticoagulant therapies. Study patients were at increased risk, and results might not apply to average-risk populations. Conclusions: Quantitative immunochemical FOBT has good sensitivity and specificity for detection of clinically significant neoplasia. Test performance in screening average-risk populations is not known.

Ann Intern Med. 2007;146:244-255.

6 ifobt performance 1462.pdf

Screening for Colorectal Neoplasms With New Fecal Occult Blood Tests: Update on Performance Characteristics

James E . Allison

Background One type of fecal occult blood test (FOBT), the unrehydrated guaiac fecal occult blood test (GT), is recommended by the United States Preventive Services Task Force and the Institute of Medicine for use in screening programs, but it has relatively low sensitivity as a single test for detecting advanced colonic neoplasms (cancer and adenomatous polyps . 1 cm in diameter). Thus, improving the sensitivity of FOBT should make colon cancer screening programs that use these tests more effective. Methods We assessed prospectively the performance characteristics of two newer FOBTs in 5841 subjects at average risk for colorectal cancer in a large group . model managed care organization. The tests evaluated included a sensitive GT, a fecal immunochemical test (FIT), and the combination of both tests. Patients with positive and negative test results were advised to have colonoscopy and sigmoidoscopy, respectively. Sensitivity and specificity for detecting advanced neoplasms in the left colon within 2 years after the FOBT screening were evaluated for the two tests administered separately and in combination. Results A total of 139 patients were diagnosed with advanced colorectal neoplasms (n = 14 cancers, n = 128 adenomas) within the 2 years following their initial FOBT screening. Sensitivity for detecting cancer was 81.8% (95% confidence interval [CI] = 47.8% to 96.8%) for the FIT alone and 64.3% (95% CI = 35.6% to 86.0%) for the sensitive GT and the combination test. Sensitivity for detecting advanced colorectal adenomas was 41.3% (95% CI = 32.7% to 50.4%) for the sensitive GT, 29.5% (95% CI = 21.4% to 38.9%) for the FIT, and 22.8% (95% CI =16.1% to 31.3%) for the combination test. Specificity for detecting cancer and adenomas was 98.1% (95% CI = 97.7% to 98.4%) and 98.4% (95% CI = 98.0% to 98.7%), respectively, for the combination test; 96.9% (95% CI = 96.4% to 97.4%) and 97.3% (95% CI = 96.8% to 97.7%), respectively, for the FIT; and 90.1% (95% CI = 89.3% to 90.8%) and 90.6% (95% CI = 89.8% to 91.4%), respectively, for the sensitive GT. Conclusions The FIT has high sensitivity and specificity for detecting left-sided colorectal cancer, and it may be a useful replacement for the GT.

J Natl Cancer Inst 2007;99: 1462 . 70

7 Faecal occult blood test-based screening programme with high compliance for colonoscopy has a strong clinical impact on colorectal cancer.

Parente F, Marino B, DeVecchi N, Moretti R; Lecco Colorectal Cancer Screening Group; Ucci G, Tricomi P, Armellino A, Redaelli L, Bargiggia S, Cristofori E, Masala E, Tortorella F, Gattinoni A, Odinolfi F, Pirola ME.

Br J Surg. 2009 May;96(5):533-40. 

Gastrointestinal Unit, Alessandro Manzoni Hospital, Lecco, Italy. f.parente@ospedale.lecco.it

BACKGROUND: The results of a pilot colorectal cancer screening programme by biennial immunochemical faecal occult blood test (FOBT) are reported. METHODS: All residents aged between 50 and 69 years in the Italian province of Lecco were invited to have a FOBT. Those with a positive result were offered colonoscopy. FOBT uptake and compliance with colonoscopy were assessed. Detection rate and positive predictive value (PPV) for cancer and adenoma were calculated. Tumour stages were compared between screen-detected cancers and other colorectal cancers diagnosed within the target age group. RESULTS: Some 38,693 (49.6 per cent) of 78,083 individuals had a FOBT and 2392 (6.2 per cent) had a positive result. Colorectal cancer was diagnosed in 4.6 per cent and advanced adenoma in 32.7 per cent. PPVs were 4.0 per cent for cancer, 28.1 per cent for advanced adenoma and 36.6 per cent for any adenoma. There was a significant difference in incidence of stage III/IV disease between screened and non-screened cohorts. Compliance for colonoscopy was 92.0 per cent. Major determinants of compliance were age less than 59 years, female sex, high education level and non-manual work. CONCLUSION: These results justify extension of colorectal cancer screening to other regions of Italy.

8 Population-based screening for colorectal cancer: Australian research and implementation.

Young GP.

J Gastroenterol Hepatol. 2009 Oct;24 Suppl 3:S33-42. 

Flinders University Centre for Cancer Prevention and Control, Adelaide, South Australia, Australia. graeme.young@flinders.edu.au

Australia is one of the first countries in the world to implement an organized whole-of-population screening program for colorectal cancer (CRC). Australians have made broad contributions to CRC in general ranging from primary prevention through genetics, secondary prevention and treatment, to palliation. This overview focuses on some of the contributions of direct relevance to population-based screening, stretching from technology development to population-based controlled studies and health services research. In terms of simple screening tests in a two-step screening strategy, the evidence is overwhelming that fecal immunochemical tests for hemoglobin (FITs) improve detection and are more acceptable. FIT-based screening is clearly acceptable to Australians and it has been demonstrated that a national organized screening program is feasible. In terms of benefit for Australians, with full roll out and high uptake by the population we could see the number of cases dying from CRC halved by this strategy. To this will be added the extra-screening benefits of improved diagnosis, improved treatment and improved public awareness, all benefits of other screening programs. CRC screening has progressed from a matter of irrelevance and distaste, to commonwealth government policy in the context of an organized program for all Australians.

9 Can patients at high risk for significant colorectal neoplasms and having normal quantitative faecal occult blood test postpone elective colonoscopy?

Hazazi R, Rozen P, Leshno M, Levi Z, Samuel Z, Waked A, Vilkin A, Maoz E, Birkenfeld S, Niv Y.

Aliment Pharmacol Ther. 2010 Feb 15;31(4):523-33. Epub 2009 Nov 19. 

Department of Gastroenterology, Rabin Medical Center, Beilinson Hospital, Petach Tikva, Israel.

BACKGROUND: Common reasons for elective screening and surveillance colonoscopy, at predetermined intervals, are family or personal history of colorectal cancer (CRC) or advanced adenoma (AAP). Quantified, human haemoglobin (Hb)-specific, immunochemical faecal occult blood tests (I-FOBT) detect bleeding. AIM: To determine I-FOBT sensitivity for CRC or AAP before elective colonoscopy in patients at high-risk of cancer or advanced adenoma. METHODS: Prospective double-blind study of 1000 ambulatory asymptomatic high-risk patients (555 family history of CRC, 445 surveillance for past neoplasm), who prepared three I-FOBTs before elective colonoscopy. I-FOBTs quantified as ngHb/mL of buffer by OC-MICRO instrument and results >or=50 ngHb/mL considered positive. RESULTS: At colonoscopy, eight patients had CRC, 64 others had AAP. Sensitivity for CRC and/or AAP was the highest, 65.3% (95% CI 54.3, 76.3), when any of the three I-FOBTs was >or=50 ngHb (15.4%), with specificity of 87.5% (95% CI 86.4, 90.5) identifying all CRCs and 62% of AAPs. CONCLUSIONS: All cancers or an AAP were detected every third I-FOBT-positive colonoscopy (47/154), so colonoscopy was potentially not needed at this time in 84.6% (846 patients). I-FOBT screening might provide effective supervision of high-risk patients, delaying unnecessary elective colonoscopies. This favourable evaluation needs confirmation and cost-benefit study by risk-group.

10 "pooled adenoma miss rate fluctuates around 22% (19–26%) [23] . With regard to CRC, miss rates range from 2 to 6% [24] . Digestion 2007;76:20–25 Colonoscopy screen.pdf

11 Ifobt and early CRC.pdf

Earlier stages of colorectal cancer detected with immunochemical faecal occult blood tests

Netherlands J Med 2009

Background: The aim of colorectal cancer screening is to improve prognosis by the detection of early cancer and precursor stages. We compared the stage distribution of asymptomatic colorectal cancer patients detected by a positive immunochemical or guaiac-based faecal occult blood test (FOBT ) with symptomatic colorectal cancer patients. Methods: In a longitudinal cohort study tumour stages were assessed in 144 symptomatic (mean age 69.3 years, 56% male) and 41 asymptomatic colorectal cancer patients (mean age 64.9 years, 56% male) of which 11 were detected with guaiac FOBT s (G-FOBT , Hemoccult-II ®) and 30 with immunochemical FOBT s (I-FOBT , OCSensor®). Stage distributions were used to calculate average stage specific predicted five-year survival rates and to analyse group differences with Wilcoxon log-rank test. Results: Colorectal cancer was detected in significantly earlier stages in symptomatic compared with asymptomatic patients (p<0.0001). Average stage specific predicted five-year survival was 59.1% in symptomatic and 76.6% in asymptomatic patients. Compared with the symptomatic patients the stage distribution for colorectal cancer patients detected with Hemoccult-II was not significantly different (p=0.29), whereas colorectal cancer was detected at significantly earlier stages with the OCSensor (p<0.0001). Treatment could be confined to colonoscopy in 27% of the asymptomatic patients compared with 3% of the symptomatic patients (p<0.0001). Cancer distribution over the colon was comparable between symptomatic and asymptomatic patients (p=0.3). Conclusions: Compared with symptomatic patients, patients detected by FOBT and especially immunochemical FOBT , presented significantly more often at earlier stages suggesting increased survival. Additionally treatment could more often be confined to colonoscopy.

12 CRC screen 1179.pdf N Engl J Med 2009;361:1179-87.

13 Numerous medical authorities, politicians, and patient advocacy groups encourage screening with colonoscopy. You can learn about the agenda of each group at http://www.amazon.com/gp/product/0814408451/.

14 n engl j med 363;11 nejm.org september 9, 2010 1076

15 Ann Intern Med. 2007;146:309-311.

16 Stat Methods Med Res. 2009 Apr;18(2):163-82. Epub 2008 Sep 2.

Cancer Research UK Centre for Epidemiology, Mathematics & Statistics, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK. fay.cafferty@cancer.org.uk

There is evidence that the removal of adenomas, by endoscopy, from the large bowel can prevent the occurrence of colorectal cancer (CRC). However, the reduction in cancer incidence due to endoscopic surveillance is difficult to estimate. Studies of cohorts of adenoma patients typically rely on comparisons with groups of historical controls. We present a model for disease progression which enables estimation of this quantity without direct comparison to a reference group. Models are applied to data from the National Polyp Study. Rates of adenoma recurrence and progression to carcinoma are estimated based on study data and relevant literature. This allows calculation of the number of cancers expected in the absence of surveillance and, thus, the number of cancers prevented. Results are compared with the original analysis. Models estimate that surveillance reduced CRC incidence by at least 97% in this cohort. The majority of the effect was due to the initial removal of adenomas rather than the follow-up surveillance. These results are similar to those produced in the original analysis when using the most appropriate reference groups. They indicate that polypectomy and follow-up surveillance can lead to large reductions in cancer incidence which may have been under-estimated in previous studies.

17 Hepatogastroenterology. 2007 Dec;54(80):2249-58.

Department of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany.

BACKGROUND/aIMS: For colorectal screening patients a gain of life time was previously calculated to be about 30-50 days. Different recommendations for recognizing at-risk groups and defining surveillance intervals after an initial finding of colorectal adenomas have been published. However, no benefit-risk analysis regarding specific long-term effects of follow-up patients has been reported to date. METHODOLOGY: A Markov model based on time-dependent transition possibilities was developed to compare two surveillance schedules: recommendations based on the Erlangen Registry of Colorectal Polyps (ERCRP) and the National Polyp Study (NPS). The outcome was calculated for a 50-year-old patient with 30 years of follow-up after initial polypectomy. The data used in this model were taken from different sources, namely the ERCRP, the German Study Group of Colorectal Cancer, the German Statistical Yearbook, and from meta-analyses of studies reporting data on complications and `sensitivity of colonoscopy. RESULTS: Patients under surveillance have a mean lifetime gain of 98 (ERCRP) and 91 (NPS) days compared with those who do not come for surveillance. Approximately 84% and 79% of deaths from colorectal carcinoma (CRC) could be prevented if patients were followed up according to the recommendations of the ERCRP and the NPS, respectively. The risk of death due to colonoscopy for patients during followup is about 0.05% lifetime risk. Sensitivity analysis showed the stability of the results under a wide range of reasonable variations of relevant parameters. In a pessimistic one-way sensitivity analysis regarding compliance, effectiveness was reduced to one third. CONCLUSIONS: Surveillance using colonoscopy is an effective tool for preventing CRC after colorectal polypectomy and similar to the screening procedure. The effectiveness is slightly higher when following the recommendations of the ERCRP, especially if a more realistic compliance is assumed.

18 "the strongest evidence favors a delay in initiation of screening in women until age 55–60 years." Digestion 2007;76:20–25 Colonoscopy screen.pdf

19 Ann Intern Med. 2008;149:627-637.

20 Ann Intern Med. 2008;149:627-637.

21 Ann Intern Med. 2007;146:309-311. Quantitative Immunochemical Fecal Occult Blood Tests: Is It Time to Go Back to the Future?

iFOBT positive editorial.pdf

22 Adenoma vs iFOBT 162.full.pdf

Hundt S, Haug U, Brenner H. Comparative evaluation of immunochemical fecal occult blood tests for colorectal adenoma detection. Ann Intern Med 2009;150:162-9. ( quoted in nej 29 variation in ifobt technology)

Of 405 colonoscopies positive for any type of adenoma, Quickvue picked up 183 and missed 222. Of 914 negative colonoscopies, Quickvue was negative in 642, positive in 272. Remember, colonoscopy can miss [http://rienstraclinic.com/newsletter/2010/2010SeptemberAppendix.html#04 ] so some of those 272 apparently falsely positive tests, probably a quarter were truly positive and the colonoscopy was incorrect. Patients with cancer were excluded from this analysis.

23 Sensitivity, but not specificity, of a quantitative immunochemical fecal occult blood test for neoplasia is slightly increased by the use of low-dose aspirin, NSAIDs, and anticoagulants.

Levi Z, Rozen P, Hazazi R, Vilkin A, Waked A, Maoz E, Birkenfeld S, Lieberman N, Klang S, Niv Y.

Am J Gastroenterol. 2009 Apr;104(4):933-8. Epub 2009 Mar 17.

Department of Gastroenterology, Rabin Medical Center, Beilinson Campus, Petach Tikvah, Israel. zohar_levi@012.net.il

OBJECTIVES: We evaluated the effect of the use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDS), and anticoagulants on the performance of immunochemical fecal occult blood test (I-FOBT). METHODS:A prospective, cross-sectional study of 1,221 ambulatory patients having total colonoscopy after preparing three I-FOBTs. Information regarding the use of medications was collected from the health medical organization (HMO) database. I-FOBT was analyzed with the OC-MICRO instrument using both >or=75 and 100 ngHb/ml of buffer thresholds to determine positivity. RESULTS: Colorectal cancer (CRC) was found in 17 and advanced adenomatous polyp (AAP) in 97 patients. A total of 212 patients were using aspirin/NSAIDS at the time of I-FOBT testing. Qualitative analysis for the detection of AAP/CRC reveals a trend for an increased sensitivity with aspirin/NSAIDS use. At the threshold 75 ng/ml for positivity, the sensitivity for the detection of AAP/CRC was 66.7% for aspirin/NSAIDS use vs. 51.2% for nondrug takers (P=0.20), and at the threshold of 100 ng/ml, the sensitivity was 66.7 vs. 46.5% (P=0.09). The specificity, however, was not affected by the use of aspirin/NSAIDS. At the threshold of 75 ng/ml for positivity, the specificity for the detection of AAP/CRC was 89.5% for aspirin/NSAIDS use vs. 91.2% for nondrug takers (P=0.47), and at the threshold of 100 ng/ml, the specificity was 92.17 vs. 93.0% (P=0.69). A total of 33 patients were using antithrombotics/coagulants at the time of I-FOBT testing. This group was small; however, it appears that their use was also associated with a trend for increased sensitivity and no change in specificity. CONCLUSIONS: The use of aspirin/NSAIDS and anticoagulants was associated with a trend for increased sensitivity with no change in specificity for the detection of AAP/CRC. This study suggests that there is no need to stop these agents before I-FOBT testing.

24 Nakama H,Zhang B,Abdul Fattah AS,Kamijo N,Fukazawa K. "Relationships between a sign of rectal bleeding and the results of an immunochemical occult blood test, and colorectal cancer [In Process Citation]" Eur J Cancer Prev. 2000 Oct;9:325-8. (Issue number 5) Research reported by Department of Public Health, Shinshu University School of Medicine, Matsumoto, Japan. hnakama@sch.md.shinshu-u.ac.jp. =15315= = Author's abstract: A cross-sectional study based on medical check-up was carried out to investigate the association between signs of rectal bleeding and colorectal cancer, and the results of an immunochemical faecal occult blood test. The 9625 patients received both an immunochemical faecal occult blood test using a two-consecutive-day method and colonoscopy. They were then divided into two groups, according to the results of a self-completed questionnaire on the signs of rectal bleeding. The positivity rate of the immunochemical faecal occult blood test as well as the positive predictive value for colorectal cancer were determined in these two groups. The faecal occult blood test was positive in 9.3% of patients with rectal bleeding and in 4.4% of patients without rectal bleeding, and the positive predictive value for colorectal cancer was 0.79 and 0.27 in patients with and without rectal bleeding, respectively. This indicates a significant difference in the positivity rate (P < 0.001) as well as the positive predictive value (P < 0.05) between these two groups. The results suggest that there are positive associations between the signs of rectal bleeding and the results of immunochemical faecal occult blood test, and between the patients presenting with rectal bleeding and colorectal cancer.

25 Ann Intern Med. 2007;146:244-255.

26 Faecal occult blood test-based screening programme with high compliance for colonoscopy has a strong clinical impact on colorectal cancer.

Parente F, Marino B, DeVecchi N, Moretti R; Lecco Colorectal Cancer Screening Group; Ucci G, Tricomi P, Armellino A, Redaelli L, Bargiggia S, Cristofori E, Masala E, Tortorella F, Gattinoni A, Odinolfi F, Pirola ME.

Br J Surg. 2009 May;96(5):533-40. 

Comment in:

  • Br J Surg. 2009 Aug;96(8):956-7; author reply 957. PMID: 19591144.

Gastrointestinal Unit, Alessandro Manzoni Hospital, Lecco, Italy. f.parente@ospedale.lecco.it

BACKGROUND: The results of a pilot colorectal cancer screening programme by biennial immunochemical faecal occult blood test (FOBT) are reported. METHODS: All residents aged between 50 and 69 years in the Italian province of Lecco were invited to have a FOBT. Those with a positive result were offered colonoscopy. FOBT uptake and compliance with colonoscopy were assessed. Detection rate and positive predictive value (PPV) for cancer and adenoma were calculated. Tumour stages were compared between screen-detected cancers and other colorectal cancers diagnosed within the target age group. RESULTS: Some 38,693 (49.6 per cent) of 78,083 individuals had a FOBT and 2392 (6.2 per cent) had a positive result. Colorectal cancer was diagnosed in 4.6 per cent and advanced adenoma in 32.7 per cent. PPVs were 4.0 per cent for cancer, 28.1 per cent for advanced adenoma and 36.6 per cent for any adenoma. There was a significant difference in incidence of stage III/IV disease between screened and non-screened cohorts. Compliance for colonoscopy was 92.0 per cent. Major determinants of compliance were age less than 59 years, female sex, high education level and non-manual work. CONCLUSION: These results justify extension of colorectal cancer screening to other regions of Italy.

27 Digestion 2007;76:20–25

Of all colorectal cancer screening methods, colonoscopy used as a primary screening tool is both the most promising and the most discussed in the current literature. Several countries have introduced colonoscopic screening on a national scale, but many issues still require further research. The practicality of using colonoscopic screening can be questionable given the huge target population, which requires a great increase in endoscopic resources. Limiting the target population by shifting the use of colonoscopy from low-risk to high-risk groups is a valid option. The quality of colonoscopy related to the individual colonoscopist’s skill has become a surprisingly considerable problem, and it is obvious that continuous quality improvement programs need to be established. The accuracy of detecting important colorectal lesions is also still influenced by the old problem of cleansing the large bowel, and further research would be welcome. Technological improvements in current endoscopic equipment will hopefully increase the diagnostic yield of colonoscopy and eventually strengthen its use.

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Medicine for People! is published by Douwe Rienstra, MD at Port Townsend, Washington.