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124 Section 3: Indications, Contraindications, Screening, and Complications in 10%; 22.5% of the procedures showed a normal colon [12]. One study reported an overall yield of 74% in 43 patients with IBD, including one nonneoplastic stenosis, but no cancer and no polyps (S. Morini, personal com- munication). Within the context of the EPAGE study, we assessed, in 6004 patients undergoing colonoscopy, the diagnostic yield of findings other than IBD in patients with known ulcerative colitis and known Crohn’s dis- ease (EPAGE study 2002, unpublished results). In 201 patients with known ulcerative colitis, we found cancer in 1%, adenomas in 3.5%, nonadenomatous polyps in 2.0%, and diverticulosis in 0.5%. In the 158 patients with known Crohn’s disease, cancer was found in 0.6%, ade- nomas in 1.3%, nonadenomatous polyps in 1.3%, and diverticulosis in 0.6%. Diagnostic yield of routine ileoscopy Intubation of the ileum is not routinely performed dur- ing colonoscopy. Ileal intubation is one way to indicate completeness of the procedure. A skilled endoscopist can inspect the terminal ileum in about 90% of cases in which such examination is needed [1]. In practice, ileoscopy is not routinely performed. A recent European multicenter trial in 6004 patients undergoing colono- scopy found that ileoscopy was performed in 29.6% of colonoscopies reaching the cecum [138]. 40 30 35 25 10 15 20 5 0 Mean + range (%) – – – – – – Cancer Adenoma IBD Fig. 11.14 Diagnostic yield of colonoscopy in patients with abdominal pain or altered bowel habit. Data from 12 studies (six prospective studies), 3252 patients. IBD in most patients. We recently studied the yield of colonoscopy in 1144 patients, among whom was a subset of 40 patients with known IBD. IBD was present in 65%, another form of colitis (infectious) in 2.5%, and stenosis Table 11.8 Diagnostic yield of colonoscopy in patients with abdominal pain or altered bowel habit. Number of Cancer Adenoma Inflammatory Diverticula Stricture Reference Comment patients (%) (%) bowel disease (%) (%) (%) Berkowitz & Kaplan [45] Abdominal pain 55 1.8 11 9.1 16.4 Abnormal bowel habit 79 1.3 10 11.4 21.5 1.3 De Bosset et al. [12] Prospective Abdominal pain 254 0.8 7 0.8 NS 2 Constipation 73 1.4 6.8 0 NS Brenna et al. [11] Prospective; gastrointestinal 117 0.8 6 2 NS 3 symptoms EPAGE study Prospective; unpublished 359 3.5 13 2.9 22.6 NS results; change in bowel habit Lasson et al. [131] Prospective; abdominal pain 281 0.7 6.8 8.9 8.5 NS Liebermann et al. [132] Nonspecific abdominal 1899 7.3 NS NS NS symptoms; polyp or mass > 1cm Mulcahy et al. [133] Abdominal pain 389 0.5 2.6 1 NS NS Neugut et al. [53] Prospective; abdominal pain 311 5 19 NS NS NS and/or change in bowel habit Pepin & Ladabaum [134] Constipation 358 2 38 NS NS NS Rex [9] All patients with one or more 75 0 31 NS NS NS negative FOBT Sardinha et al. [135] Patients > 80 years; abdominal 107 2 NS NS NS NS pain; change in bowel habit Schmitt et al. [136] Prospective; abdominal pain 794 0.6 7.7 2.6 NS NS Total 3252* 1.6* 12.6* 3.2 FOBT, fecal occult blood test; NS, not stated. * Excluding data from Liebermann et al. [132]. Chapter 11: Diagnostic Yield of Colonoscopy by Indication 125 adenomas greater than 1 cm in diameter. Furthermore, barium enema was falsely positive in 14%. In a large nonrandomized controlled trial [88] in 21 000 patients aged over 40 years, barium enema missed 25% of the lesions found at colonoscopy. Insufficient procedural competence and experience on the part of the endoscopist may decrease the value of colonoscopy [145]. Even in expert hands, there is a significant miss rate of polyps. Rex and colleagues [146] performed two colonoscopies on the same day (back-to- back colonoscopy) in 183 patients randomly assigned to the same or another endoscopist. The overall miss rate of adenomas was 24%; it was 27% for adenomas ≤ 5 mm, 13% for adenomas 6–9 mm, and 6% for adeno- mas ≥ 1 cm. Although considered as the gold standard in the diagnostic armamentarium of colonic disease, the performance characteristics of colonoscopy are not optimal, even in the hands of an expert operator and under ideal conditions. The quality and diagnostic reliability of the procedure are further dependent on several other factors. Much emphasis has been placed on the duration of colonoscopy and in particular on the time needed to reach the cecum. Overall duration may be significant with respect to pro- cedural efficiency in a context of cost constraints, waiting lists at endoscopy units, and the need for endoscopists and endoscopes. However, it is not acceptable that an overly rapid endoscopic technique should render the procedure less tolerable or reduce its diagnostic reliab- ility. Withdrawal time seems to be more critical for diag- nostic yield, particularly colonic distension, adequate suctioning and cleaning, and adequate time spent exam- ining the colon. The quality of withdrawal is critical for the detection rate of adenomas [147]. In fact, it has been shown very recently that individual endoscopists’ In one study in 138 consecutive colonoscopies, ileo- scopy revealed a diagnosis in eight patients (6%). In half of these patients, the diagnosis was made based on ileoscopy alone. The yield of ileoscopy was 2.7% in asymptomatic patients undergoing screening colono- scopy and 29% in patients complaining of diarrhea [139]. Another prospective study in 295 consecutive patients [140] reported macroscopic abnormalities of the ileum in 4 of 213 patients (1.8%) in whom ileoscopy was possible, one-quarter of whom also had abnormal histology of the ileal mucosa (0.5%). However, this study did not indic- ate patient symptoms. Ileoscopy is obviously particu- larly useful in patients with symptoms suggesting IBD in order to exclude isolated ileal disease or to facilitate the differential diagnosis between Crohn’s disease and ulcerative colitis [141]. Furthermore, ileoscopy seems to be indicated in patients with chronic diarrhea, especially in HIV-positive patients [142]. Diagnostic reliability of colonoscopy Colonoscopy is more sensitive than barium enema and allows biopsies and endoscopic therapy. The sensitivity of barium enema and colonoscopy for diagnosing colo- rectal cancer was 84% and 95% in a recent retrospective study [143]. A controlled and blinded comparison of both procedures was made in the National Polyp Study where 580 patients underwent 862 paired examinations [144]. Barium enema detected a polyp in only 39% of cases in which a polyp was subsequently found during colonoscopy, and in only 48% in patients with advanced (a) (b) 40 30 35 25 10 15 20 5 0 Mean + range (%) Cancer Adenoma IBD 40 30 35 25 10 15 20 5 0 Mean + range (%) – – – – – – Fig. 11.15 Diagnostic yield of colonoscopy in patients with abdominal pain or altered bowel habit: (a) EPAGE; (b) all studies. 126 Section 3: Indications, Contraindications, Screening, and Complications up after cancer resection, and positive FOBT have a high diagnostic yield (Fig. 11.16). In contrast, nonbleeding colonic symptoms (diarrhea, abdominal pain, altered bowel habit) and surveillance after polypectomy have a lower yield of cancer (Fig. 11.16). Incidence rates of colo- rectal cancer increase consistently with age. Patient age is thus an important predictor of colorectal cancer in patients referred for colonoscopy. The yield in the detection of adenomas is less de- pendent on the indications than the detection of cancer, due to the high prevalence of polyps found in screening colonoscopies or in patients with nonspecific symptoms. The adenoma detection rate is highest in the follow-up of polyps, follow-up of cancer, in patients with positive FOBT (Fig. 11.16), and in nonemergency lower gastroin- testinal bleeding (see Fig. 11.2). IBD is a relatively com- mon finding in hematochezia and diarrhea. Although diagnostic yield is important, it must be kept in mind that colonoscopy may also be beneficial to patients if it excludes a clinically relevant lesion by con- ferring reassurance. References 1 Marshall JH, Barthel JS. The frequency of total colonoscopy and terminal ileal intubation in the 1990s. Gastrointest Endosc 1993; 39: 518–20. 2 Rex DK, Bond JH, Winawer S et al. Quality in the technical performance of colonoscopy and the continuous quality improvement process for colonoscopy: recommendations of the U.S. Multi-Society Task Force on Colorectal Cancer. Am J Gastroenterol 2002; 97: 1296–308. 3 Bat L, Williams CB. Usefulness of pediatric colonoscopes in adult colonoscopy. Gastrointest Endosc 1989; 35: 329–32. 4 Rex DK, Weddle RA, Lehman GA, Pound DC, O’Connor KW, Hawes RH. Flexible sigmoidoscopy plus air-contrast procedure times correlate with the rate at which they identify multiple or clinically significant polyps [148]. We recently assessed technical aspects of performance of colonoscopy in 6004 European patients referred for colonoscopy [138]. The mean overall duration of colono- scopy was 22.8 min, including a mean withdrawal time of 10.1 min. In the same study, we found that colon cleans- ing quality was highly associated with the total duration of the procedure (P < 0.001), the difficulty of colonoscopy (P < 0.001), and the overall yield of relevant endoscopic diagnoses (P = 0.002), particularly of adenomas (P < 0.001) (EPAGE study 2002) [149]. Summary For the clinician, the yield of relevant diagnoses is one of the most important outcomes of a diagnostic procedure such as colonoscopy. While appropriateness of indica- tions refers to the quality of the indication, the diagnostic yield refers to endoscopic lesions that are potentially rel- evant to the patient’s care, in conjunction with clinical symptoms and signs. Unfortunately, the relationship between endoscopic findings and clinical presentation is imperfect, particularly in light of the fact that endoscopic lesions (e.g. polyps) may be asymptomatic [150]. 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Diagnostic yield of routine ileoscopy. Am J Gastroenterol 1995; 90: 1441–3. 140 Kundrotas LW, Clement DJ, Kubik CM, Robinson AB, Wolfe PA. A prospective evaluation of successful terminal ileum intubation during routine colonoscopy. Gastrointest Endosc 1994; 40: 544–6. 141 Geboes K, Ectors N, D’Haens G, Rutgeerts P. Is ileoscopy with biopsy worthwhile in patients presenting with symp- toms of inflammatory bowel disease? Am J Gastroenterol 1998; 93: 201–6. 142 Gonvers JJ, Bochud M, Burnand B, Froehlich F, Dubois RW, Vader JP. Appropriateness of colonoscopy: diarrhea. Endoscopy 1999; 31: 641–6. 143 Rex DK, Rahmani EY, Haseman JH, Lemmel GT, Kaster S, Buckley JS. Relative senitivity of colonoscopy and barium enema for detection of colorectal cancer in clinical practice. Gastroenterology 1997; 112: 17–23. 144 Winawer S, Stewart ET, Zauber AG et al. A comparison of colonoscopy and double-contrast barium enema for surveillance after polypectomy. N Engl J Med 2000; 342: 1766–72. 145 Winawer SJ, Fletcher RH, Miller L et al. Colorectal cancer screening: clinical guidelines and rationale. Gastroentero- logy 1997; 112: 1060–3. 146 Rex DK, Cutler CS, Lemmel GT et al. Colonoscopic miss rates of adenomas determined by back-to-back colono- scopies. Gastroenterology 1997; 112: 24–8. 147 Rex DK. Colonoscopic withdrawal technique is associated with adenoma miss rates. Gastrointest Endosc 2001; 51: 33–6. 148 Sanchez W, Petersen BT, Herrick L. Evaluation of diag- nostic yield in relation to procedure time of screening or sur- veillance colonoscopy. Gastrointest Endosc 2002: 55: A213. 149 Froehlich F, Gonvers JJ, Vader JP, Wietlisbach V, Burnand B. and the EPAGE study group. Impact of colon cleansing on quality and diagnostic yield of colonoscopy: EPAGE European multicenter study. Gastrointest Endosc 2003; 57: AB104. 150 Froehlich F, Burnand B, Vader JP, Gonvers JJ. Endoscopies: too many and not enough! Endoscopy 1997; 29: 652–4. 118 Hobbs FDR, Cherry RC, Fielding JWL et al. Acceptability of opportunistic screening for occult gastrointestinal blood loss. BMJ 1992; 304: 483–6. 119 Dupont HL. Guidelines on acute infectious diarrhea in adults. Am J Gastroenterol 1997; 92: 1962–75. 120 Kalra L, Hamlyn AN. Comparative evaluation of invest- igations for colorectal carcinoma in symptomatic patients. Postgrad Med J 1988; 64: 666–8. 121 Fine KD, Seidel RH, Do K. The prevalence, anatomic distri- bution, and diagnosis of colonic causes of chronic diarrhea. Gastrointest Endosc 2000; 51: 318–26. 122 Patel Y, Pettigrew NM, Grahame GR, Bernstein CN. The diagnostic yield of lower endoscopy plus biopsy in non- bloody diarrhea. Gastrointest Endosc 1997; 46: 338–43. 123 Shah RJ, Fenoglio-Preiser Bleau BL, Giannella RA. Use- fulness of colonoscopy with biopsy in the evaluation of patients with chronic diarrhea. Am J Gastroenterol 2001; 96: 1091–5. 124 Marshall JB, Singh R, Diaz-Arias AA. Chronic, unex- plained diarrhea: are biopsies necessary if colonoscopy is normal? Am J Gastroenterol 1995; 90: 372–6. 125 Prior A, Lessells AM, Whorwell PJ. Is biopsy necessary if colonoscopy is normal? Dig Dis Sci 1987; 32: 673–6. 126 Yusoff IF, Ormonde DG, Hoffmann NE. Routine colonic mucosal biopsy and ileoscopy increases diagnostic yield in patients undergoing colonoscopy for diarrhea. J Gastro- enterol Hepatol 2002; 17: 276–80. 127 Bernstein CN, Ridell RH. Colonoscopy plus biopsy in the inflammatory bowel diseases. Gastrointest Endosc Clin North Am 2000; 10: 755–71. 128 Bini EJ, Cohen J. Diagnostic yield and cost-effectiveness of endoscopy in chronic human immuno-deficiency virus related diarrhoea. Gastrointest Endosc 1998; 48: 354–61. 129 Bond JH. Is referral for colonoscopy underutilized by primary care physicians? Gastrointest Endosc 2000; 52: 693– 6. 130 De Bosset V, Gonvers JJ, Vader JP, Dubois RW, Burnand B, Froehlich F. Appropriateness of colonoscopy: lower abdom- inal pain or constipation. Endoscopy 1999; 31: 637–40. 131 Lasson A, Kilander A, Stotzer PO. Diagnostic yield of colonoscopy based on symptoms. Gastroenterology 2002; 55: A266. 132 Liebermann DA, De Garmo PL, Fleischer DE, Eisen GM, Chan BKS, Helfand M. Colonic neoplasia in patients with nonspecific GI symptoms. Gastrointest Endosc 2000; 51: 647–51. 133 Mulcahy HE, Patel RS, Mohkashi MS et al. Low yield of significant pathology when colonoscopy is performed for isolated abdominal pain: a multicenter database analysis of 15,550 patients. Gastrointest Endosc 2000: 51: A135. 134 Pepin C, Ladabaum U. The yield of lower endoscopy in patients with constipation: survey of a university hospital, a public county hospital, and a Veterans Administration medical center. Gastrointest Endosc 2002; 56: 325–32. 131 itself should be the preferred screening test [8], others have argued that it should be one of several screening options [4,7,9]. This chapter reviews the rationale for considering colonoscopy as a primary screening test in average-risk populations and discusses implementation issues includ- ing compliance, resources, and cost. Rationale for screening Screening with colonoscopy should be considered in the context of other screening tests. For each test we should ask the following questions. 1 What is the likelihood that the test will detect the target lesion (advanced adenoma or early cancer)? 2 Are there programmatic issues, such as need for repeat testing, which impact effectiveness? 3 What are the potential harms? Fecal occult blood test Three randomized controlled trials have compared population screening using the fecal occult blood test (FOBT) with no screening [11–13]. Although there were differences in study methods, the findings are consistent across all the studies. Cancers are detected at earlier stages in screened compared with unscreened subjects, and this translates into significant mortality reduction of 15–33% over time [11–13]. Rehydration of FOBT slides increases sensitivity but reduces specificity, so that many more patients will receive colonoscopy for false- positive results over time. In the Minnesota study [11], 38% of subjects in the FOBT arm received colonoscopy during the first 13 years of the study. One analysis has suggested that some of the benefit of the FOBT could be explained by random assignment to screening colo- noscopy [14]. In the Veterans Affairs (VA) Cooperative Study [15], average risk subjects (n = 2885) had both one-time rehydrated FOBT and screening colonoscopy. FOBT was positive in 50% of patients with cancer, consistent with other studies [16,17]. However, among patients with advanced neoplasia without invasive cancer (defined as adenoma with high-grade dysplasia or villous histology, Introduction Colorectal cancer (CRC) is the second leading cause of cancer death in North America and western Europe [1]. As populations live longer due to advances in medicine and public health, rates of CRC are likely to increase. The biology of CRC offers an opportunity for both early detection and prevention. Most cancers evolve from pre- malignant adenomas over a period of many years; spread of malignancy from the colon to sites outside the colon likewise occurs over years. Screening of asymp- tomatic populations has demonstrated that cancers can be detected at early, more curable stages compared with unscreened controls. Furthermore, studies have demon- strated that detection and removal of premalignant adenomas can prevent incident cancers [2,3]. Therefore, if screening tests could identify patients with high-risk adenomas, many cancers could be prevented, mortality reduced, and the burden of caring for patients with can- cer diminished. If the target of screening is the advanced adenoma, we should ask: how effectively do screening tests identify patients with advanced adenomas? There is consensus that colonoscopy should be the preferred screening test for individuals known to have higher than average risk [4]. Higher-risk categories include individuals with familial hereditary syndromes (familial polyposis, hereditary nonpolyposis CRC), chronic colitis due to ulcerative colitis or Crohn’s dis- ease, and a family history of CRC in a first-degree relat- ive. Patients with a personal history of adenoma or cancer should receive colonoscopic surveillance, and are not considered part of a screening cohort. Recent studies [5,6] have raised questions about whether colonoscopy should also be a preferred screening test in average-risk individuals. The perform- ance characteristics of several screening modalities in average-risk populations have been scrutinized by the United States Preventive Services Task Force (USPSTF) and by expert multidisciplinary panels [4,7–10]. All the expert panels strongly recommend that population screening should begin for average-risk individuals at age 50 years. They have noted that colonoscopy is more effective than other screening tests for polyp detection. Although some experts have argued that colonoscopy Chapter 12 Screening Colonoscopy: Rationale and Performance David Lieberman Colonoscopy Principles and Practice Edited by Jerome D. Waye, Douglas K. Rex, Christopher B. Williams Copyright © 2003 Blackwell Publishing Ltd 132 Section 3: Indications, Contraindications, Screening, and Complications reduce CRC mortality, particularly from tumors in the distal colon. An important limitation is that a large por- tion of the colon is not examined at sigmoidoscopy. If most patients with advanced neoplasia in the proximal colon had index adenomas in the distal colon, which would lead to complete colonoscopy, then sigmoido- scopy would be a sensitive screening test. Two screening colonoscopy studies reported the find- ings of complete colonoscopy, and estimated the poten- tial findings of screening sigmoidoscopy in average-risk subjects [5,6]. Advanced neoplasia was more likely to be found in the distal colon (55% in the Indiana study; 53% in the VA study). Both studies found that more than 50% of patients with advanced proximal neoplasia (beyond the reach of the sigmoidoscope) would not have been identified with sigmoidoscopy, even assuming that any index adenoma would lead to colonoscopy. In addition, both studies found that as average-risk subjects age, they are more likely to harbor advanced proximal neoplasia and that these are less likely to be identified with sigmoi- doscopy alone. Sigmoidoscopy is able to detect advanced adenomas and early cancers in the area examined. The key limita- tion of sigmoidoscopy is that a large portion of the colon is not examined; some patients with advanced proximal neoplasia would go undetected. There is also concern that with increasing age, sigmoidoscopy may be less effective. Combined flexible sigmoidoscopy and FOBT The American Cancer Society has long recommended screening with both FOBT and flexible sigmoidoscopy beginning at age 50 years [9], among other options. Intuitively, this combined approach should have a greater impact on CRC mortality than either test alone. In one study [23], patients were offered sigmoidoscopy with or without FOBT. Although the patients were not randomly assigned to groups, the groups were com- parable. Follow-up was irregular and compliance with follow-up testing poor. During the 9-year follow-up, 144 cases of CRC were found but only 28 were actually detected through screening. The major finding was that patients screened with both FOBT and sigmoidoscopy had better long-term survival after detection of cancer compared with controls, suggesting a benefit from evalu- ation of positive screening tests. The overall mortality rate of the two groups was similar. In the VA Cooperative Study [15], combined screening with one-time FOBT and sigmoidoscopy would have identified 76% of patients with advanced neoplasia, only slightly better than sigmoidoscopy alone (70%). With increasing age, there was a trend for decreasing efficacy of the combined screening approach. Modeling [24–26] has suggested that the combined approach could be or tubular adenoma ≥ 1 cm), FOBT was positive in only 21.6%. Moreover, it is likely that if rehydration had not been used, the positive rate would have been lower. These results suggest that one-time FOBT has serious lim- itations for detection of high-risk adenomas. If FOBT is to be used for screening, a program of repeat screening must be developed. Compliance with repeat screening is poor. There is some concern that patients may be falsely reassured after a negative test, and not return for repeat testing [7]. If the FOBT is positive, there is consensus that patients should undergo complete colonoscopy. This represents a second step during which compliance can break down. These studies support the hypothesis that population screening of average-risk subjects could reduce CRC mortality. FOBT is a poor test for detection of advanced adenomas. Although there is some evidence that screen- ing with FOBT can lead to reduction in cancer incidence (due to polyp detection and removal) [3], this reduction is modest. The need for frequent repeat testing and appropriate follow-up of positive tests with colonoscopy represent important program limitations. Flexible sigmoidoscopy There is evidence from two case–control studies [18,19] that exposure to sigmoidoscopy is associated with a reduction in colon cancer mortality, in that portion of the colon examined. In these studies, patients with death due to CRC were ascertained and an age-matched control group without CRC was used for comparison. Selby and colleagues [18] compared 261 patients with fatal rectosigmoid cancers (within reach of the sigmoi- doscope) to 868 age- and sex-matched controls; 8.8% of cases had sigmoidoscopy compared with 24.2% of con- trols, suggesting that endoscopic sigmoid screening could reduce the risk of fatal cancers within the range of the sigmoidoscope (odds ratio 0.41). Moreover, the benefit remained strong even when the most recent examination was 9–10 years earlier. Newcomb and col- leagues [19] found similar results. Both studies did not find that sigmoidoscopy reduced the likelihood of fatal cancers of the right colon, perhaps because such tumors would not be readily detected with sigmoi- doscopy. Muller and Sonnenberg [20] reported another case–control study in a VA population to determine the impact of either sigmoidoscopy or colonoscopy on CRC risk. Compared with controls, patients with CRC were less likely to have had prior endoscopic examinations of the colon (odds ratio 0.51 for colon cancer; 0.55 for rectal cancer). Two ongoing randomized trials using flexible sigmoidoscopy will report findings in the next few years [21,22]. These case–control data provide compelling evid- ence that screening sigmoidoscopy could substantially Chapter 12: Screening Colonoscopy: Rationale and Performance 133 The case for screening with colonoscopy Rationale Colonoscopy can examine the entire colon in more than 90–95% of procedures, if performed by a fully trained endoscopist. Polypectomy can be performed at the same time. Given these obvious advantages, we should ask: why not perform screening colonoscopy? Arguments against screening with colonoscopy General criteria for screening tests applied to the popula- tion are summarized in Table 12.1. Colonoscopy is an invasive and expensive test. The risk of perforation, seri- ous bleeding, and cardiopulmonary events is low when performed by experienced endoscopists (0.3–0.5%), but if applied to the general population could account for considerable morbidity [29]. If only 5–6% of the adult population will develop CRC during life, most patients will not benefit from colonoscopy. Ideal screening would target colonoscopy at the patients most likely to have advanced neoplasia or cancer, and would not employ an expensive invasive test to populations with a relat- ively low pretest probability of disease. However, the ideal simple test has been elusive. Lacking the perfectly sensitive and adequately specific noninvasive screening test, screening with colonoscopy is now recommended as a screening option by all expert panels in the USA, though not in Canada, Europe, or Australia. Arguments for screening with colonoscopy Relative to other screening tests, there is substantial evidence that colonoscopy is very accurate for detection of significant neoplasia. In two tandem colonoscopy studies, in which patients had two colonoscopies per- formed during the same session, the miss rate for polyps greater than 1 cm was less than 10% [30,31]. Since these studies were performed by experts, it is possible that in clinical practice more lesions are missed by less expert endoscopists. Specificity for detection of neoplasia ap- proaches 100%, because biopsies are usually obtained that confirm the histologic presence of neoplasia. The ability to prevent incident cancers or reduce mortality with primary screening colonoscopy has never been tested in a clinical trial. However, there are several lines of indirect evidence which endorse the potential effectiveness of colonoscopy. First, the FOBT trials all recommended colonoscopy as the follow-up test after a positive FOBT. It was colonoscopy which identified the early cancers that led to a survival advantage in screened populations. Lang and Ransohoff [14] per- formed a posthoc analysis of the Minnesota FOBT study, in which 38% of subjects in the screened group received more effective and less costly than other screening approaches if tests are performed programmatically and on a regular basis, as is recommended (annual FOBT and sigmoidoscopy every 5 years). However, the models require assumptions about compliance with initial test- ing and follow-up colonoscopy after positive tests, which may not be realistic in clinical practice. Radiographic colon imaging with barium, computed tomography and magnetic resonance imaging No large studies have evaluated colon imaging with barium in an average-risk population. The USPSTF rates barium as “unknown” with regard to effectiveness in reducing incidence and mortality from CRC, and only “fair” with regard to ability to detect cancer and advanced neoplasia. The National Polyp Study found that the sensitivity of barium studies for detection of polyps larger than 1 cm was 48% [27]. The data on computed tomography or magnetic resonance imaging of the colon are preliminary and the technology is still evolving. The range of sensitiv- ity for large polyps is 40–96%, suggesting wide vari- ation in either skill or technique. Currently, no review panel has recommended screening with these modal- ities, although they have captured the attention of the public. Possible future tests There are other screening modalities that show promise. When specific gene mutations were identified in patients with familial polyposis (adenomatous polyposis coli gene on chromosome 5) and hereditary nonpolyposis CRC (mismatch repair gene mutations), there was great hope that molecular genetics would provide a simple blood test to risk-stratify otherwise average-risk sub- jects. Such screening was touted to the public in the New York Times in the 1990s. The reality of genetic testing to date has been sobering, but there has been recent pro- gress. Several groups have identified genetic mutations in stool samples. If tumors slough cells with genetic mutations into the bowel lumen and if these mutations can be identified, it may be possible to select individuals for colonoscopy based on the stool profile. This “needle in a haystack” approach is complicated by the fact that there is no single mutation which identifies all high-risk patients. New tests that search for several of the most common genetic alterations associated with CRC are under study [28]. With the development of the Human Genome Project has come the science of proteomics: understanding of the relationship of a gene mutation to specific protein product. If altered protein products are circulating in the blood, it may be possible to screen patients with blood tests. [...]... sigmoidoscopy ($) Costs of colonoscopy ($) Cost of care for CRC ($) Total costs ($) 0 0 0 136 452 922 136 452 922 5 497 809 0 33 640 016 115 715 7 53 154 8 53 577 0 1 63 3 13 218 16 281 508 89 619 575 269 214 30 1 0 0 41 091 209 1 03 124 901 144 216 110 0 0 189 667 598 34 1 13 230 2 23 780 829 ∞ 81 678 9705 74 032 36 509 55 38 6 2981 28 1 43 10 9 83 Cost-effectiveness ACER costs/saved life-years ($) ICER compared... Inadomi JM The cost-effectiveness of colonoscopy in screening for colorectal cancer Ann Intern Med 2000; 133 : 5 73 – 84 4 Weinstein MC, Stason WB Foundations of cost-effectiveness for health and medical practices N Engl J Med 1977; 296: 716–21 5 Tengs TO, Adams ME, Pliskin JS et al Five-hundred lifesaving interventions and their cost-effectiveness Risk Anal 1995; 15: 36 9–90 6 Lieberman DA Cost-effectiveness... + (1 – P) × Colonoscopy < Colonoscopy [ 13. 2] Simple algebraic manipulations yield: Alternative < P × Colonoscopy [ 13. 3] In essence, any alternative test procedure needs to cost less than colonoscopy multiplied by the expected frac- 145 tion of subjects with normal findings For instance, expecting 30 % of all subjects at age 50 years to harbor polyps and a colonoscopy to cost $1000, P = 70% and the alternative... age N Engl J Med 2002; 34 6: 1781– 5 45 Rex DK, Cummings OW, Helper DJ et al 5-year incidence of adenomas after negative colonoscopy in asymptomatic average-risk persons Gastroenterology 1996; 111: 1178– 81 Colonoscopy Principles and Practice Edited by Jerome D Waye, Douglas K Rex, Christopher B Williams Copyright © 20 03 Blackwell Publishing Ltd Chapter 13 Cost-effectiveness of Colonoscopy Screening... implementation Gastrointest Endosc 2001; 54: 662–7 35 Winawer SJ, Zauber AG, O’Brien MJ et al Randomized comparison of surveillance intervals after colonoscopic removal of newly diagnosed adenomatous polyps N Engl J Med 19 93; 32 8: 901–6 36 Rex DK Colonoscopy: a review of its yield for cancers and adenomas by indication Am J Gastroenterol 1995; 90: 35 3– 65 37 Lieberman DA Cost-effectiveness model for colon cancer... administered for polypectomy and to evaluate the remainder of the colon Chapter 13: Cost-effectiveness of Colonoscopy Screening Alternative procedure P 1-P P Negative: $0 Positive: $colonoscopy Negative: $0 Colonoscopy 1-P Positive: $0 Fig 13. 5 Decision tree for calculating the threshold probability when a test becomes a viable alternative to colonoscopy Both procedures (colonoscopy or its alternative)... between $28 000 and $82 000 When compared with no prevention, single colonoscopy, FOBT, and decennial colonoscopy are associated with the smallest ICER and appear the most cost-effective strategies Compared with no screening, a single colonoscopy represents a very cost-effective screening strategy of less 144 Section 3: Indications, Contraindications, Screening, and Complications Table 13. 1 Outcomes of... Sigmoidoscopy Single colonoscopy Decennial colonoscopy Effectiveness Expected number of CRC without screening Number of prevented CRC Life-years saved Reduction in mortality (%) 5904 0 0 0 5904 926 1896 18 5904 2027 36 36 34 5904 135 2 2604 23 5904 4428 7952 75 Resource utilization Number of FOBT Number of sigmoidoscopies Number of colonoscopies 0 0 0 2 464 606 0 69 794 0 6 23 597 27 31 9 0 0 86 184 0 0 36 5 456 Costs... 1994; 35 : 1419– 23 35 Connell WR, Lennard-Jones JE, Williams CB Factors affecting the outcome of endoscopic surveillance for cancer in ulcerative colitis Gastroenterology 1994; 107: 934 –44 36 Provenzale D, Shaerin M, Phillips-Bute BG et al Healthrelated quality of life after ileoanal pull-through: evaluation and assessment of new health status measures Gastroenterology 1997; 1 13: 7–14 150 Section 3: Indications,... degree of benefit that would justify the risk and resource utilization For colonoscopy to be effective, the examinations will need to be accurate and complete, and performed with minimal risk The overall success rate and risk of colonoscopy in community practice is unknown and requires study Future advances in colonoscopy technology may improve success rates and reduce risk The “holy grail” of screening . al. [ 133 ] Abdominal pain 38 9 0.5 2.6 1 NS NS Neugut et al. [ 53] Prospective; abdominal pain 31 1 5 19 NS NS NS and/ or change in bowel habit Pepin & Ladabaum [ 134 ] Constipation 35 8 2 38 NS. cancer. N Engl J Med 2000; 34 3: 16 03 7. 138 Section 3: Indications, Contraindications, Screening, and Complications 35 Winawer SJ, Zauber AG, O’Brien MJ et al. Randomized com- parison of surveillance. N Engl J Med 19 93; 32 8: 901–6. 36 Rex DK. Colonoscopy: a review of its yield for cancers and adenomas by indication. Am J Gastroenterol 1995; 90: 35 3– 65. 37 Lieberman DA. Cost-effectiveness model

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