Motion – Colonoscopic surveillance is more cost effective ...downloads.hindawi.com/journals/cjgh/2003/149259.pdf · surveillance colonoscopy:Dysplasia is, by definition, a neoplastic

Can J Gastroenterol Vol 17 No 2 February 2003122

Motion – Colonoscopic surveillance is more costeffective than colectomy in patients with ulcerative

colitis: Arguments against the motionAnders Ekbom MD PhD1,2

This article was originally presented at a symposium entitled, “Controversies in Gastroenterology”, sponsored by Axcan Pharma, Toronto, Ontario,April 8 to 10, 2002

1Unit of Clinical Epidemiology, Department of Medicine, Karolinska Hospital, Stockholm, Sweden; 2Department of Epidemiology, Harvard Schoolof Public Health, Boston, Massachusetts, USA

Correspondence: Dr A Ekbom, Department of Medical Epidemiology, Karolinska Institutet, Box 281, 171 77 Stockholm, Sweden. Telephone 46-8-08-728-61-90, fax 46-8-08-31-49-75, e-mail [email protected]

A Ekbom. Motion – Colonoscopic surveillance is more costeffective than colectomy in patients with ulcerative colitis:Arguments against the motion. Can J Gastroenterol2003;17(2):122-124.

There are insufficient data upon which to base recommendationsabout surveillance colonoscopy and prophylactic colectomy for theprevention of colorectal cancer in patients with ulcerative colitis.Case series, analyses of intermediate results and extrapolations fromother patient groups do not constitute reliable evidence. Availablestudies are susceptible to several biases: the ‘healthy worker’ effect,surveillance bias and selection bias. Patients who are enrolled in sur-veillance programs are more likely to be thoroughly evaluated before-hand, are more likely to be given a diagnosis of dysplasia or neoplasmeven when asymptomatic and are more likely to comply with medicaltreatment, including maintenance anti-inflammatory medication.Comparisons of the rates of neoplasia or death between surveyed andnonsurveyed patients are, therefore, of questionable validity.Prophylactic colectomy, unlike surveillance colonoscopy, preventsdeath from colorectal cancer. Moreover, it is difficult to keep patientsin surveillance programs, and those who withdraw from programsappear to be at high risk of developing cancer. Prophylactic colecto-my should be strongly considered for patients with dysplasia, scleros-ing cholangitis, longstanding pancolitis (especially if it began early inlife) or a positive family history of colorectal cancer. This procedureis underused in clinical practice and is a good alternative to colono-scopic surveillance in high risk patients.

Key Words: Colonoscopy; Cost effective; Ulcerative colitis

Motion – La surveillance par coloscopie estplus rentable que la colectomie chez lespatients atteints de rectocolite hémorragique :Arguments contre la motion

RÉSUMÉ : Il n'existe pas suffisamment de données permettant de for-muler des recommandations sur la coloscopie de contrôle et la colectomieprophylactique pour la prévention du cancer colorectal chez les patientsatteints de rectocolite hémorragique. Des séries de cas, des analyses derésultats intermédiaires et des extrapolations à partir d'autres groupes depatients ne constituent pas des sources fiables de données. Les étudesactuelles sont susceptibles de biais : effet du " travailleur bien portant ",biais de surveillance, biais de sélection. Il y a de fortes chances que lessujets qui participent aux programmes de surveillance soient soumis aupréalable à une évaluation complète, reçoivent un diagnostic de dysplasieou de néoplasme même avant l'apparition de symptômes ou respectent letraitement médical, y compris la prise d'anti-inflammatoires d'entretien.Les comparaisons des taux de néoplasie et de mortalité entre patientsétudiés et patients non étudiés soulèvent donc des doutes. La colectomieprophylactique, contrairement à la coloscopie de contrôle, prévient lamort attribuable à un cancer colorectal. De plus, il est difficile de garderles patients dans les programmes de surveillance et ceux qui s'en retirentsemblent fortement prédisposés au cancer. La colectomie prophylactiquedevrait être sérieusement envisagée chez les patients qui présentent unedysplasie, une cholangite sclérosante, une pancolite de longue date(surtout si elle est apparue à un jeune âge) ou qui ont des antécédentsfamiliaux de cancer colorectal. L'intervention est négligée en pratiqueclinique et pourtant elle offre une bonne solution de rechange à la sur-veillance par coloscopie chez les patients à risque élevé.

Reliable cost-benefit analyses require valid data. Such dataare lacking in the case of colonoscopic surveillance pro-

grams for patients with ulcerative colitis (UC). Instead, wemust rely on historical data, case series reported by clinicianswith vested interests and inferences based on other patientgroups. Models can be constructed, but they are subject to widevariations in underlying assumptions (1). It is, therefore, veryeasy to make a case against colonoscopic surveillance inpatients with UC. This does not mean, however, that I recom-mend prophylactic colectomy for all patients with longstand-ing disease, even though there are subgroups for whom Iseriously consider this option.

MORBIDITY AND MORTALITYThe main goal of surveillance colonoscopy in patients withUC is to prevent death from colorectal cancer (2). In theory,this goal can be attained by the detection of either dysplasia orearly colon cancer, followed by curative surgery. Unfortunately,there are no randomized clinical trials comparing the mortali-ty from colorectal cancer in patients with UC who have under-gone colonoscopic surveillance, prophylactic colectomy orclinical follow-up without colonoscopy. We have only caseseries, usually from referral centres. They have generallyinvolved a comparison of intermediate outcomes, such as Duke

CONTROVERSIES IN GASTROENTEROLOGY

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stage, between cancers that are discovered by surveillance andthose that are found clinically (3-6). Alternatively, the dura-tion of survival after a diagnosis of colorectal cancer can bedetermined for cancers detected within and outside of surveil-lance programs (3). These approaches, however, are suscepti-ble to methodological problems, including the ‘healthy worker’effect, surveillance bias and selection bias.

Patients enrolled in surveillance programs usually havebeen subjected to a clinical evaluation, including a bariumenema and/or colonoscopy, before entering the program.Patients who are not selected for surveillance, or who refuse toenter a program, are probably not evaluated as thoroughly.Therefore, patients who enter programs tend to be healthierbefore enrolment than are other patients, making it difficult tocompare the two groups.

It is impossible to determine the prevalence of asymptomaticneoplastic lesions in patients who have not undergone surveil-lance. This makes any comparison of the frequency of neoplasticlesions in surveyed and nonsurveyed patients invalid.

Maintenance therapy with anti-inflammatory drugs, such assulfasalazine or mesalazine, seems to decrease the risk of col-orectal cancer in patients with UC (7,8). There is evidencethat patients in surveillance programs are more likely to com-ply with maintenance therapy than are those who do notundergo surveillance. Lynch et al (9) made the followingobservation: “A review of the notes of our cancer patients sug-gests that virtually none of them were on disease suppressivedrugs, such as salazopyrine, regularly or at all.”

The presence of this confounding factor puts into questionany evaluation of the beneficial effect of surveillance programs.

Data from observational studies concerning the impact ofsurveillance colonoscopy on intermediate outcomes, such ascancer morbidity or dysplasia, should be interpreted withextreme caution. Bernstein et al (10) stated:

“A risk benefit ratio and cost-effectiveness of dyspla-sia surveillance cannot be properly analyzed with exist-ing data. Until further studies are done that adequatelyaddress the limitations of existing studies, the true costand benefit for the population as a whole remainsunknown.”

Since it was written in 1994, no new data have emergedthat contradict this statement.

WHAT DO WE KNOW?The following is a summary of some of the data that are rele-vant to this discussion:

1. Death from colorectal cancer accounts for the excessmortality in most follow-up studies of patients with UC(11).

2. Patients who undergo prophylactic colectomy will not diefrom colorectal cancer.

3. Follow-up studies have found that prophylactic colectomydoes not adversely affect the quality of life of patients withUC (12).

4. Some patients in surveillance programs die from colorectalcancer (3,5).

5. The only population-based study that found no excess inmortality from colorectal cancer was conducted inCopenhagen (13). The Danish investigators adopted astrategy of maintenance therapy with anti-inflammatorydrugs and a low threshold for colectomy, but undertook nocolonoscopic surveillance. Although it is impossible togauge the relative benefits of colectomy and maintenancetherapy on cancer mortality, the favourable results in thisstudy are noteworthy.

6. Only one observational study, a case-control study fromSweden, assessed the effect of colonoscopic surveillance onmortality from colorectal cancer (14). There was astatistically insignificant trend toward benefit fromsurveillance, but it was very difficult to keep patients inthe program. A high drop-out rate was noted after just oneor two surveillance procedures. Other investigators havefound that patients who stop undergoing surveillancecolonoscopy are much more likely to die from colorectalcancer than are those who remain in programs (5,9).These reports do not necessarily reflect a beneficial effectof surveillance; patients who withdraw from programsmight also require fewer maintenance drugs or be lesscompliant with medical therapy.

It is, therefore, quite possible that colonoscopic surveillanceis used mainly by patients who need it least. An unknownnumber of patients require alternative strategies, includingprophylactic colectomy.

WHO SHOULD UNDERGO PROPHYLACTICCOLECTOMY?

There are at least four categories of UC patients who should beseriously considered for prophylactic colectomy.

1. Patients in whom dysplasia has been detected bysurveillance colonoscopy: Dysplasia is, by definition, aneoplastic lesion. Its presence signifies a high risk ofcolorectal cancer, either at the time of the initial biopsy orsubsequently (15). Dysplasia will not disappear withfollow-up colonoscopies, and there is no treatment thatcauses it to regress.

2. Patients with pancolitis of more than 10 years’ duration,and in whom a history of colorectal cancer is present ina first degree relative: These patients have twoindependent risk factors for colorectal cancer. The riskis even greater if the first degree relative developedcancer before the age of 50 years (16). The importanceof a family history of colorectal cancer to the risk ofcolitis-associated cancer has been confirmed in animalmodels (17).

3. Patients with primary sclerosing cholangitis: Patientswith primary sclerosing cholangitis have an especially highrisk of developing colorectal cancer. In a Swedish study,the cumulative incidence of colorectal cancer 10 yearsafter the diagnosis of primary sclerosing cholangitis was16% (18).

Cost effectiveness of colonoscopy versus colectomy in UC

Can J Gastroenterol Vol 17 No 2 February 2003 123


4. Patients with pancolitis and whose disease began beforeage 15 years: Although there still is controversy about thedegree of risk in this group (19), these patients wouldharbour pancolitis for, on average, at least 60 years. Thereis no evidence that they would not be at high risk ofcancer when they become older. Of note, one of the fewdeaths from colorectal cancer in the Copenhagen study(13) occurred in a patient in this subgroup.

Patients in these categories should be fully informed of theoption of prophylactic colectomy.

CONCLUSIONProphylactic colectomy is an underused procedure in patientswith UC. Surveillance colonoscopy should not be consideredthe optimal approach to the prevention of colorectal cancer inthese patients.

Ekbom

Can J Gastroenterol Vol 17 No 2 February 2003124

REFERENCES1. Delcò F, Sonnenberg A. A decision analysis of surveillance for

colorectal cancer in ulcerative colitis. Gut 2000;46:500-6. 2. Zack MM, Ekbom A, Persson PG, Adami HO. Evaluation of

surveillance programmes for colorectal cancer in ulcerative colitispatients by case-control studies: Methodological considerations. J Med Screen 1997;4:137-41.

3. Choi PM, Nugent FW, Schoetz DJ Jr, Silverman ML, Haggitt RC.Colonoscopic surveillance reduces mortality from colorectal cancerin ulcerative colitis. Gastroenterology 1993;105:418-24.

4. Löfberg R, Broström O, Karlén P, Tribukait B, Öst A. Colonoscopicsurveillance in long-standing total ulcerative colitis – A 15-yearfollow-up study. Gastroenterology 1990;99:1021-31.

5. Lennard-Jones JE, Melville DM, Morson BC, Ritchie JK, Williams CB. Precancer and cancer in extensive ulcerative colitis:Findings among 401 patients over 22 years. Gut 1990;31:800-6.

6. Lashner BA, Kane SV, Hanauer SB. Colon cancer surveillance inchronic ulcerative colitis: Historical cohort study. Am J Gastroenterol 1990;85:1083-7.

7. Pinczowski D, Ekbom A, Baron J, Yuen J, Adami HO. Risk factorsfor colorectal cancer in patients with ulcerative colitis: A case-control study. Gastroenterology 1994;107:117-20.

8. Eaden J, Abrams K, Ekbom A, Jackson E, Mayberry J. Colorectalcancer prevention in ulcerative colitis: A case-control study.Aliment Pharmacol Ther 2000;14:145-53.

9. Lynch DAF, Lobo AJ, Sobala GM, Dixon MF, Axon AT. Failure ofcolonoscopic surveillance in ulcerative colitis. Gut 1993;34:1075-80.

10. Bernstein CN, Shanahan F, Weinstein WM. Are we tellingpatients the truth about surveillance colonoscopy in ulcerativecolitis? Lancet 1994;343:71-4.

11. Ekbom A, Helmick CG, Zack M, Holmberg L, Adami HO.Survival and causes of death in patients with inflammatory boweldisease: A population-based study. Gastroenterology 1992;103:954-60.

12. Thompson-Fawcett MW, Richard CS, O’Connor BI, Cohen Z,McLeod RS. Quality of life is excellent after a pelvic pouch forcolitis-associated neoplasia. Dis Colon Rectum 2000;43:1497-502.

13. Langholz E, Munkholm P, Davidsen M, Binder V. Colorectalcancer risk and mortality in patients with ulcerative colitis.Gastroenterology 1992;103:1444-51.

14. Karlén P, Kornfeld D, Broström O, Löfberg R, Persson PG, Ekbom A. Is colonoscopic surveillance reducing colorectal cancermortality in ulcerative colitis? A population based case controlstudy. Gut 1998;42:711-4.

15. Lindberg B, Persson B, Veress B, Ingelman-Sundberg H, Granqvist S. Twenty years’ colonoscopic surveillance of patientswith ulcerative colitis. Detection of dysplastic and malignanttransformation. Scand J Gastroenterol 1996;31:1195-204.

16. Askling J, Dickman PW, Karlén P, Broström O, Lapidus A, Löfberg R,Ekbom A. Family history as a risk factor for colorectal cancer ininflammatory bowel disease. Gastroenterology 2001;120:1356-62.

17. Bertone ER, Giovannucci EL, King NW Jr, Petto AJ, Johnson LD.Family history as a risk factor for ulcerative colitis-associated coloncancer in cotton-top tamarin. Gastroenterology 1998;114:669-74.

18. Kornfeld D, Ekbom A, Ihre T. Is there an excess risk for colorectalcancer in patients with ulcerative colitis and concomitant primarysclerosing cholangitis? A population based study. Gut 1997;41:522-5.

19. Ekbom A. Risk factors and distinguishing features of cancer in IBD.Inflam Bowel Dis 1998;4:235-43.


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Motion – Colonoscopic surveillance is more cost effective ...downloads.hindawi.com/journals/cjgh/2003/149259.pdf · surveillance colonoscopy:Dysplasia is, by definition, a neoplastic