Colonoscopy Principles and Practice - part 8 pps

459 Introduction Patients who have undergone resection of one or more colorectal adenomatous polyps may have an increased risk for recurrent adenomas and subsequent cancer, and therefore may benefit from long-term follow-up surveil- lance. Lacking reliable scientific data, physicians in the past often performed this surveillance incorrectly, too frequently, or for the wrong patients. Many physicians still adhere strictly to a routine surveillance program that they learned in the past for all their postpolypectomy patients, rather than trying to use current data to assess risk and tailor follow-up to the specific features of each case. Inappropriate surveillance can result in enorm- ous costs of time, resources, and patient inconvenience or risk. Rex and Lieberman [1] reported that in 1999 4.4 million colonoscopies were performed in the USA. An analysis using the large CORI national endoscopic database indicated that at least 17%, or about 750 000 of these examinations, are performed annually for follow- up surveillance after resection of colorectal polyps [2]. Obviously if we miscalculate the type and frequency of follow-up surveillance, we will either put many patients at unnecessary risk for developing colorectal cancer or waste considerable scarce healthcare resources. It is now generally accepted that in western coun- tries over 95% of colorectal cancers arise in benign adenomatous polyps that develop and grow slowly in the colon over many years before they turn cancerous [3]. Pathologic correlations indicate that malignancy does not occur in hyperplastic polyps, rarely occurs in small tubular adenomas, and is more common in tubul- ovillous and villous adenomas as they increase in size. A patient with one known adenoma in the large bowel has a 30–50% likelihood of harboring a second syn- chronous adenoma elsewhere in the colon at that time, and a 30–50% likelihood of developing a metachronous adenoma sometime in the future [4]. For these reasons (the adenoma to cancer relation- ship and the appreciable incidence of synchronous and metachronous adenomas), most endoscopists practice some form of follow-up surveillance for their polyp patients. The ultimate objective of this surveillance is to detect and resect clinically significant missed syn- chronous adenomas and new metachronous adenomas before they can turn cancerous and harm the patient. The key questions that need to be addressed in design- ing appropriate follow-up strategies are: What is each patient’s risk of colorectal cancer after resection of one or more benign adenomatous polyps, and will post- polypectomy surveillance eliminate or substantially reduce that risk? This chapter reviews the rationale and current recommendations for postpolypectomy sur- veillance, emphasizing the need to tailor surveillance strategies to the carefully considered individualized assessment of risk for each patient. Colonoscopy is the procedure of choice for postpolypectomy surveillance Colonoscopy is clearly the preferred method for post- polypectomy surveillance for most patients. It is sub- stantially more accurate than double-contrast barium enema for the detection of polypoid lesions of all sizes. An earlier, carefully controlled, single-blinded study comparing the accuracy of the two examinations per- formed in the same patients demonstrated a sensitivity for detecting polyps of 67% and 94% for double-contrast barium enema and colonoscopy respectively [5]. More recently, the National Polyp Study reported the results of a similarly controlled comparison of both methods in a large cohort of patients actually undergoing post- polypectomy surveillance [6]. A total of 862 back-to-back double-contrast barium enema examinations and colo- noscopies were performed in 680 patients. Expert radio- logists or colonoscopists who were blinded to the result of the alternative examination performed all exam- inations. Barium enema studies were positive in only 39% of patients found to have adenomatous polyps at colonoscopy. Even when patients had adenomas that were 1 cm or more in diameter, the barium enema was negative in 52%. False-positive barium enemas occurred in 14% of cases. A retrospective analysis of cancer cases in 20 medical centers in Indiana showed an accuracy of colonoscopy and barium enema for detecting can- cers of 95% and 83% respectively [7]. In a subset of colonoscopies in this study that were performed by gastroenterologists, who presumably had more training Chapter 39 Postpolypectomy Surveillance John H. Bond Colonoscopy Principles and Practice Edited by Jerome D. Waye, Douglas K. Rex, Christopher B. Williams Copyright © 2003 Blackwell Publishing Ltd 460 Section 10: Malignant Polyp, Post-Polypectomy & Post-Cancer Surveillance and experience, the sensitivity for detecting cancer was 97%. The entire colon and rectum can be thoroughly exam- ined by colonoscopy performed by experienced endo- scopists, with minimal discomfort in over 95% of cases. Most importantly, colonoscopy is both diagnostic and therapeutic, allowing resection of most detected polyps at a single sitting with a single bowel-cleansing prepara- tion. Although the alternative strategy of performing barium enema plus flexible sigmoidoscopy initially may be less costly, the need to do subsequent colonoscopy for those with positive findings makes this approach, on average, equally expensive. The complication rate for colonoscopy is appreciably higher than that of barium enema; however, major complications including per- foration are rare provided the examination is performed by a well-trained experienced endoscopist [8]. Computed tomography (CT) colonography (“virtual colonoscopy”) is now being studied for follow-up sur- veillance of patients with colorectal cancer or polyps. CT colonography has already been shown to be more accur- ate than double-contrast barium enema for detecting polyps. In addition, some but not all studies indicate that this method is nearly as accurate as colonoscopy for detecting large (≥ 1 cm) polypoid adenomas, although accuracy rapidly drops off for medium-sized and small polyps. The published sensitivity of CT colonography for detecting large adenomas (≥ 1 cm) in three experi- enced centers in the USA was 75.2–91% [9–11]. However, not all centers currently performing virtual colonoscopy can achieve this level of accuracy. For example, a recent multicenter study in the USA reported that the sensit- ivity for detecting 1-cm polyps in over 500 patients in nine centers ranged from about 8 to 83% [12]. In the best US studies, the sensitivity of virtual colonoscopy for detecting medium-sized polyps (5–10 mm) was only 47.2–82%. A major limitation of virtual colonoscopy compared with conventional colonoscopy is that, as with barium enema, the study is only diagnostic. Whenever a suspicious lesion or a clinically significant neoplasm is found, the patient must undergo a subsequent colono- scopy to confirm and/or resect the lesion. The need to do two expensive tests would make surveillance costly and inconvenient. The follow-up endoscopy must usually be scheduled on a different day and therefore the patient must undergo a second bowel-cleansing preparation. Risk of cancer following polypectomy Two earlier studies from the Mayo Clinic estimated the risk of cancer after polypectomy. In 1984, Spencer and colleagues [13] reported the results of 10 000 person- years of follow-up of 751 patients who had undergone resection of a single small (≤ 1 cm) polyp from the distal colon during rigid proctosigmoidoscopy. There was no apparent increased incidence of subsequent cancer in this group compared with that of the local age-matched population. In contrast, the same group of investigators reported 2 years later that patients with larger adenomas (> 1 cm) had a risk of developing metachronous cancer that was 2.7 times greater than expected, and those with multiple index adenomas had a relative risk that was five times greater than expected [14]. Another study of the risk of cancer after removal of rectosigmoid adenomas was reported in l992 from St Mark’s Hospital, London, by Atkin and colleagues [15]. A group of 1618 patients who had rectosigmoid adenomas resected during proctosigmoidoscopy with no further colonic surveillance were followed for a mean of 14 years (22 462 person-years). Patients with index adenomas that were tubulovillous, villous, or large (≥ 1 cm) had a 3.6- fold increased subsequent incidence of colorectal can- cer. However, those with only small tubular adenomas (< 1 cm), whether single or multiple, had a subsequent incidence of cancer that was less than that of the age- matched general population. These investigators con- cluded that follow-up surveillance may be warranted in patients with tubulovillous, villous, or large adenomas, particularly if these adenomas were multiple. However, in patients with small tubular adenomas, surveillance may not be of value because the risk of subsequent can- cer is so low. Lastly, an important prospective postpolypectomy colonoscopy study was performed by Grossman and colleagues [16] on 544 asymptomatic subjects with a past history of adenomas found at screening proctosigmoi- doscopy. In 142 patients whose worst index lesion was a single small (< 10 mm) tubular adenoma and who had no first-degree relatives with colorectal cancer, the prevalence of advanced neoplasia (defined as tubular adenomas ≥ 1 cm, tubulovillous or villous adenomas, or adenomas with high-grade dysplasia or invasive cancer) was only 3%, no greater than would be expected in the general population. In contrast, subgroups with advanced or multiple index lesions had prevalences of advanced adenomas ranging from 8 to 18%. Concept of the advanced adenoma These follow-up experiences, as well as a large and increasing volume of information about the molecular genetic basis for the adenoma–carcinoma sequence, are increasingly shifting the emphasis away from simply finding and harvesting large numbers of clinically insig- nificant small tubular adenomas toward strategies that focus on ways to reliably detect and resect the less com- mon, but clinically much more dangerous, advanced adenoma (Table 39.1). Defined by both the National Polyp Study and several earlier studies such as that of Grossman and colleagues [16], an advanced adenoma Chapter 39: Postpolypectomy Surveillance 461 is one that is either large (≥ 1 cm) or contains the ad- vanced histologic features of villous change, high-grade dysplasia, or invasive carcinoma [17]. Large numbers of small simple tubular adenomas develop in large numbers of people: over 30% of the population over age 50 years have these lesions, yet only a small fraction will ever develop colorectal cancer. While it is obvious that all large adenomas were small at some time, most small tubular adenomas never grow, advance, and turn malignant. Colonic carcinogenesis is a complex, non- linear, multistep process occurring over many years that results from the progressive accumulation of genetic mutations and chromosomal deletions [18]. As neoplasia proceeds from normal-appearing mucosa, through small, medium and large benign adenomas, and finally to invasive cancer and metastases, genetic changes are found in increasing number. An adenomatous polyp is a monoclonal derivative of a single epithelial stem cell that either inherits (familial neoplasia) or acquires (sporadic neoplasia) the first of these many genetic alterations. Each additional genetic “hit,” probably caused by noxi- ous environmental carcinogenic factors, leads to a new clone of daughter cells with a growth advantage that allows the clone to take over the developing polyp. The reason most small simple tubular adenomas stay small and clinically benign is because they never develop the additional genetic alterations (i.e. oncogene mutations and tumor-suppressor gene alterations) needed to make them advance. A large volume of high-quality scientific evidence published during the past decade indicates that colonoscopic resection of an advanced adenoma is both predictive of recurrent metachronous advanced adenomas during postpolypectomy follow-up surveil- lance and is a highly effective way of preventing colorec- tal cancer [19]. Thus, our postpolypectomy efforts need to increasingly focus on ways to reliably find and resect advanced adenomas before they turn to cancer. Outcomes and observational studies underscore the different behavior of small tubular adenomas and ad- vanced adenomas. In an earlier study by Hoff and col- leagues [20], 215 polyps less than 5 mm in diameter were left in situ in 112 individuals for a 2-year follow-up period to ascertain their growth rate. At the end of the 2 years, 49% of adenomas had increased in size and 14% had regressed. Although total adenoma mass had increased by 136%, none had grown to a size greater than 5 mm and none had developed high-grade dysplasia or carcinoma. In a more recent study from Japan, Obata and colleagues [21] marked 139 small polyps (3–10 mm) with India ink and followed them with yearly colono- scopy. During a mean follow-up period of 33 months, 135 (97%) did not change in form or size. These workers also concluded that small polyps do not appreciably change over 3 years and they advance very slowly if at all. In contrast to these observational studies of the nat- ural history of small polyps, there is considerable evid- ence that large polyps behave more aggressively. Eide [22] reported that the risk of developing carcinoma in a 1-cm adenoma was 3% per year in a Norwegian popu- lation. The National Polyp Study found a strong relationship between adenoma size and the prevalence of high-grade dysplasia: the odds ratio for high-grade dysplasia in a large polyp (≥ 1 cm) was 20.3 compared with that of a diminutive polyp (≤ 5 mm) [23]. Likewise, many reported series of polyp cases indicate a strong linear correlation between adenoma size, more extensive villous configuration, more severe dysplasia, and the presence of invasive carcinoma [24]. Such advanced adenomas also contain a larger fraction of the genetic mutations and chromosomal changes commonly found in the fully developed cancer phenotype [18]. Lastly, the classic study by Stryker and colleagues [25] clearly showed the considerable malignant potential of large adenomas. Before the availability of colonoscopy, 226 patients who had large (> 1 cm) polyps detected on barium enema but refused their removal by surgery were followed for up to 20 years. Follow-up of these untreated patients showed that 37% of the polyps enlarged, 21 invasive carcinomas developed at a polyp site, and 11 carcinomas developed at another site. The cumulative risk of cancer at 5, 10, and 20 years was 2.5, 8, and 24%, respectively. This study supports the need to find and excise all large colorectal polyps and the need for periodic surveillance of these patients to identify metchronous adenomas at a site in the colon remote from the index polyp. Missed synchronous vs. metachronous polyps Adenomas found by colonoscopy in virtually all re- ported postpolypectomy surveillance series are gener- ally smaller than those resected at the initial colonoscopy examination [26]. While it is impossible to reliably differ- entiate between true recurrent adenomas and missed synchronous ones during follow-up colonoscopy, many undoubtedly were missed by the index examination. Direct determination of the colonoscopy miss rate for polyps was evaluated in two prospective “tandem” Table 39.1 Advanced adenoma. Size 1 cm or larger in diameter Histology Villous change High-grade dysplasia Invasive carcinoma 462 Section 10: Malignant Polyp, Post-Polypectomy & Post-Cancer Surveillance colonoscopy studies. Hixson and colleagues [27] per- formed a study in which two colonoscopists performed same-day back-to-back colonoscopies in 90 subjects after a single bowel-cleansing preparation. The investigators alternated the endoscopist who would perform the first examination, during which detected lesions were docu- mented but not removed. The study reported a miss rate for small (≤ 5 mm) and medium-sized (6–9 mm) polyps of 16 and 12% respectively; however, no large polyps (≥ 1 cm) went undetected. A similarly designed tandem colonoscopy study by Rex and colleagues [28] reported a miss rate for small (≤ 5 mm), medium (6–9 mm), and large (≥ 1 cm) polyps of 27, 13, and 6%, respectively, in 183 patients. In order to differentiate between true recurrent and missed synchronous adenomas following surveillance colonoscopy, Hixson and colleagues [29] performed 2-year follow-up examinations in 58 of the original 90 patients who had undergone tandem colonoscopies. In 38% of these 58 patients 56 adenomas were detected, 31 of which were judged to be new metachronous lesions, defined as a follow-up polyp found in a colonic segment in which a prior lesion of the same histologic classification had not been previously detected during the tandem colonoscopies. Three of these adenomas were large (≥ 1 cm), and therefore the authors concluded that, while most metachronous adenomas found at 2 years of follow-up are small tubular adenomas, large ones can develop in normal-appearing mucosa in that time period. The miss rate and true 1-year recurrence rate of colorectal adenomas was also determined in a population of patients reflecting a broad spectrum of dif- ferent gastroenterology practice settings within the con- text of two large prospective chemoprevention studies carried out by the Polyp Prevention Study Group [30]. The miss rate was determined by comparing findings for patients who had repeat colonoscopies within 120 days, both of which had good preparation and were com- plete to the cecum. The true 1-year recurrence rate was determined by subtracting this miss rate from the rate of adenoma detection at colonoscopy performed 1 year later as per the study protocol. The adenoma miss rate per patient was 8% and the 1-year recurrence rate was 28%. The authors concluded that there is a significant colonoscopic miss rate for neoplastic polyps at initial colonoscopy as well as a substantial postpolypectomy recurrence rate within 1 year of a clearing colonoscopy. Frequency of postpolypectomy colonoscopic surveillance The decision about who needs surveillance influences the cost of a surveillance program more than the decision about how often to do follow-up surveillance colono- scopy. When colonoscopic polypectomy was introduced in the early 1970s, performing yearly follow-up exam- inations became the standard even though its yield appeared to be small and was not supported by scientific evidence. For this reason the National Polyp Study (Table 39.2) was designed by a joint committee of the American Gastroenterology Association, the American Society for Gastrointestinal Endoscopy, and the Amer- ican College of Gastroenterology [31]. Many of the current recommendations for postpolypectomy surveil- lance are based on this 10-year prospective, multicenter, landmark study funded by the National Cancer Institute and directed by Winawer. The main objective of the study was to determine if follow-up colonoscopic exam- inations performed at 3 years after initial polypectomy were as effective in detecting clinically important colonic neoplasia as follow-up evaluations at 1 and 3 years. Patients undergoing colonoscopy in each of the seven participating centers were eligible for the study if they had no personal or family history of colorectal polyps or cancer. From this group, patients were invited to enroll in the investigation if they had one or more adenomas resected that were less than 3 cm in diameter and did not contain invasive carcinoma, and if the colonoscopist believed that all polyps had been resected at the time of the index colonoscopy. A total of 1418 patients were randomly assigned to have either follow-up colonoscopy at 1 and 3 years and then every 3 years, or just a follow- up colonoscopy every 3 years after the initial poly- pectomy. The percentage of patients who had adenomas found by 3 years in the group examined at 1 and 3 years was 41.7% compared with 32% for the group examined only at 3 years [32]. However, the number of patients who had advanced adenomas by 3 years was the same in each group (3.3%) (Table 39.3). The study therefore concluded that an interval of at least 3 years is recom- mended before the first surveillance colonoscopy is performed after resection of colorectal adenomas. The further follow-up of both groups at 3-year intervals also showed that if the first 3-year follow-up revealed no new adenomas, subsequent follow-up could be safely extended to 5-year intervals. Table 39.2 National Polyp Study design (seven participating centers, 1418 patients). Patient eligibility No personal or family history of colorectal polyps or cancer One or more adenomas removed on initial colonoscopy (a) Less than 3 cm in diameter (b) No invasive cancer All polyps removed at that time Patients randomized into two follow-up arms Colonoscopy at 1 year and 3 years Colonoscopy at 3 years only Chapter 39: Postpolypectomy Surveillance 463 Repeat clearing colonoscopy after polypectomy Before embarking on a postpolypectomy surveillance program that prescribes follow-up colonoscopy in 3– 5 years, the entire large bowel should first be thoroughly examined to clear it of all detectable synchronous lesions. A repeat clearing examination may be indicated for patients with an incomplete initial colonoscopy or for one done with a suboptimal bowel preparation. A sec- ond clearing examination should also be considered for selected patients with multiple polyps when the colono- scopist is concerned that clinically significant lesions may have been missed. Repeat clearing colonoscopy to insure complete poly- pectomy is essential after piecemeal resection of large sessile polyps. Such polyps often contain appreciable amounts of villous tissue with a high malignant poten- tial, and they tend to recur locally after colonoscopic resection even in cases where the initial polypectomy appeared to be complete. A second clearing colonoscopy should be performed in 3–6 months to confirm that resection was complete. Residual neoplastic tissue has been reported in up to one-third of cases after piecemeal snare resection of sessile polyps greater than 2 cm in diameter [33]. If polyp tissue persists after two or three examinations, good-risk patients should usually be referred for surgical resection. When patients are found to have these large sessile polyps, they need to be edu- cated at the time of initial diagnosis about the import- ance of complying with the entire course of management and follow-up. Most experienced colonoscopists have witnessed tragic cases in which a patient was partially treated by piecemeal snare polypectomy, was then lost to follow-up, and returned later with an advanced can- cer at the polyp site. Effect of polypectomy on cancer incidence and mortality It is difficult to assess the effect of postpolypectomy surveillance on the subsequent incidence and mortal- ity of colorectal cancer because it is nearly impossible to separate the effect of the initial polypectomy from the effect of follow-up colonoscopic surveillance. It is now clear, however, that resecting advanced adenomat- ous polyps, both initially and during postpolypectomy follow-up, is a powerful way to prevent cancer. Cohort and case–control studies of the effect of large bowel endoscopy have strongly indicated that polypectomy reduces the subsequent incidence and mortality of colo- rectal cancer located in the examined segment. Many years ago, Gilbertsen and Nelms at the University of Minnesota [34] reported that annual rigid proctoscopic screening and removal of rectal polyps performed in 21 000 volunteers over a 20-year period reduced the incidence of rectal cancer by 85%. Case–control studies of the effect of screening proctosigmoidoscopy by Selby and colleagues [35] and Newcomb and colleagues [36] suggested a reduction in mortality from distal cancer of 60 and 80% respectively. Lastly, a large case–control study involving over 32 000 veterans by Muller and Sonnenberg [37] indicated that patients who had flexible sigmoidoscopy, colonoscopy, and polypectomy had a 50% reduced risk of developing colorectal cancer. Most convincing is the landmark analysis by Winawer and colleagues [38] from the National Polyp Study. All 1418 subjects enrolled in the study were pooled to deter- mine the effect of initial polypectomy plus follow-up surveillance colonoscopies performed every 3 years. Only five new cancers were detected during an average follow-up of about 7 years (8400 person-years), which was 76–90% lower than expected by comparison with three reference populations. Thus, for the first time, a well-designed prospective trial showed that colono- scopic removal of all adenomas in the colon and rectum successfully interrupted the adenoma–cancer sequence, preventing most cancers from developing. Two recent reports from Europe confirm the findings and con- clusions of the National Polyp Study. The Telemark Polyp Study from Norway [39] showed in a randomized controlled trial that colonoscopy and polypectomy for those with a positive screening flexible sigmoidoscopy reduced the subsequent incidence of colorectal cancer by 80%. A multicenter Italian study followed 1693 patients who had undergone resection of at least one adenoma greater than 5 mm in diameter [40]. The incidence of metachronous cancer was compared with that of a refer- ence population. After a mean follow-up of 10.5 years (14 211 person-years), only six colorectal cancers were detected, indicating a reduction in incidence due to polypectomy of 76%. Investigators from the National Polyp Study recently performed a Micro-Simulation Screening Modeling Analysis (MISCAN) to predict the incidence of colorectal cancer using data from the study [41]. The model demonstrated a dramatic reduction in expected colo- rectal cancer incidence and indicated that the initial polypectomy accounted for the major component of this incidence reduction. The model predicted a modest benefit from postpolypectomy surveillance after 6 years. This conclusion is consistent with the fact that many Table 39.3 National Polyp Study results. Total adenomas Advanced Group at 3 years (%) adenomas (%) Follow-up at 1 year and 3 years 41.7 3.3 Follow-up at 3 years 32 3.3 464 Section 10: Malignant Polyp, Post-Polypectomy & Post-Cancer Surveillance more advanced adenomas were resected in the study at the index colonoscopy compared with the number found and resected during follow-up. Further stratification of postpolypectomy cancer risk Estimates by pathologists as well as an analysis of all patients undergoing colonoscopy in the seven centers of the National Polyp Study indicate that it takes, on aver- age, 10–12 years for an adenoma to develop, advance, and turn to cancer [42,43]. The cumulative recurrence rate of advanced adenomas in this trial was low: 4% at 3 years and 8% at 6 years [44]. Because of the long natural history of the adenoma–carcinoma sequence and the overall low recurrence rate of advanced adenomas in follow-up studies, recent analyses have focused on ways to safely lengthen postpolypectomy intervals for most patients. Further analysis of follow-up data from the National Polyp Study and data from more recent out- come studies of postpolypectomy surveillance now indicate that it is possible to stratify risk of recurrent advanced adenomas based on patient characteristics and the findings at initial polypectomy [45]. In the National Polyp Study, patients with a relatively high risk of developing advanced adenomas during follow- up included those with multiple adenomas (three or more), large adenomas (> 1 cm), or age over 60 years at initial adenoma diagnosis plus a parent with colo- rectal cancer. Patients with a low risk of metachronous advanced adenomas included those with only one or two small adenomas and no family history of colorectal cancer. Other studies suggest other predictors for recurrence of adenomas. The Polyp Prevention Study Group deter- mined predictors for metachronous adenomas in 479 patients who had one or more polyps detected at their index colonoscopy and then had repeat colonoscopies 1 and 4 years later in a negative chemoprevention trial of antioxidant vitamins [46]. Multivariate analysis showed that multiple adenomas (three or more) or at least one tubulovillous adenoma at initial colonoscopy was asso- ciated with an increased incidence of multiple adenomas at follow-up. In this study, no factors predicted an in- creased incidence of advanced metachronous adenomas. Another follow-up analysis was performed using the Cleveland Clinic Adenoma registry of 697 patients who had an adenoma recurrence within 3 years of a positive baseline colonoscopy [47]. Having three or more aden- omas on initial colonoscopy, with at least one measuring 1 cm or larger, greatly increased the chance of finding an advanced adenoma at the first 3-year follow-up surveil- lance colonoscopy. Conversely, patients with only one or two adenomas, all measuring less than 1 cm, were at extremely low risk of having an important adenoma within 3 years. More recently, the Polyp Prevention Trial, a negative randomized trial of the effect of diet on the recurrence of colorectal adenomas, reported a recur- rence rate of advanced adenomas at 4 years of 16% [48]. Baseline predictors of a higher risk of metachronous advanced adenomas included age over 65 years, proximal location of baseline adenomas, and villous histology. Current colorectal cancer screening and surveil- lance guidelines recommend that clinicians assess each patient’s risk of developing metachronous advanced adenomas and tailor postpolypectomy surveillance strategies accordingly [49,50]. Based on the available clinical and pathologic data reviewed in this chapter, patients with colorectal adenomas can now be strati- fied into high- and low-risk groups. After the colon has been satisfactorily cleared of all synchronous adenomas, repeat colonoscopy is recommended in 3 years for patients who are at high risk. These include those who at baseline colonoscopy have (i) large (≥ 1 cm) or multiple (three or more) adenomas, (ii) an adenoma with the advanced pathologic features of villous change, high- grade dysplasia, or invasive carcinoma, and (iii) those over age 60 years with a parent with colorectal cancer. Patients with a low risk of metachronous advanced adenomas include those who initially have only one or two small (< 1 cm) tubular adenomas without high- grade dysplasia or cancer, and no significant family history of colorectal cancer. For these low-risk patients, the first postpolypectomy follow-up colonoscopy can be safely delayed for at least 5 years or, in the case of advanced age or significant comorbidity, no follow-up may be indicated. Surveillance for this low-risk group is controversial. Some argue that since their risk of subsequent colorectal cancer does not appear to meas- urably exceed that of the average-risk population, no surveillance is indicated. Many, however, noting the discrepant findings in the different follow-up studies, are uncomfortable eliminating all surveillance for these patients. Postpolypectomy surveillance recommendations A comprehensive evidence-based polyp guideline was recently prepared by the Practice Parameters Committee of the American College of Gastroenterology entitled “Polyp guideline: diagnosis, treatment, and surveillance for patients with colorectal polyps” [50]. This guideline was also endorsed by the American Society for Gastro- intestinal Endoscopy and the American Gastroentero- logy Association. The following are this guideline’s recommendations for postpolypectomy surveillance. 1 Complete colonoscopy should be done at the time of initial polypectomy to detect and resect all synchronous adenomas. Chapter 39: Postpolypectomy Surveillance 465 2 Additional clearing examinations may be required after resection of a large sessile adenoma, or if (because of multiple adenomas or other technical reasons) the colonoscopist is not reasonably confident that all aden- omas have been found and removed. 3 After a complete clearing colonoscopy has been accomplished following an initial polypectomy, repeat colonoscopy to check for metachronous adenomas should be performed in 3 years for patients at high risk for developing metachronous advanced adenomas. This includes those who at baseline examination have multiple (more than two) adenomas, a large (≥ 1 cm) adenoma, an adenoma with villous histology or high- grade dysplasia, or a family history of colorectal cancer. 4 Repeat colonoscopy to check for metachronous aden- omas should be performed in 5 years for most patients at low risk for developing advanced adenomas. This includes those who at baseline examination have only one or two small tubular adenomas (< 1 cm) and no family history of colorectal cancer. 5 Selected patients at low risk for metachronous advanced adenomas may not require follow-up surveillance. 6 After one negative follow-up surveillance colonoscopy, subsequent surveillance intervals may be increased to 5 years. 7 If doing surveillance colonoscopy is not feasible, flexible sigmoidoscopy followed by a double-contrast barium enema is an acceptable alternative. 8 Follow-up surveillance should be individualized according to the age and comorbidity of the patient, and should be discontinued when it seems unlikely that follow-up is capable of prolonging quality of life. Cost and cost-effectiveness of postpolypectomy surveillance Adoption of these recommendations would substanti- ally reduce the cost of postpolypectomy surveillance because many clinicians still perform surveillance more frequently than is necessary. For example, Ransohoff and colleagues [51] estimated that postpolypectomy surveillance that leads only to the detection and resec- tion of small tubular adenomas is unlikely to appreci- ably reduce colorectal cancer incidence or mortality. They performed a cost-effectiveness analysis of available data and concluded that the cost of surveillance of those with a low subsequent risk of colorectal cancer, such as those with a single small tubular adenoma, is pro- hibitive. Based on their assumptions in 1991, it would cost $80 000–300 000 per life saved for a surveillance pro- gram of colonoscopy every 3 years for all 50-year-old patients with small adenomas followed for 30 years. In another cost-effectiveness mathematical modeling analysis, Lieberman [52] concluded that conventional postpolypectomy surveillance comprises 19–34% of the total cost of a colorectal cancer screening program. According to his calculations, if postpolypectomy sur- veillance focused solely on the detection of advanced adenomas, this cost could be reduced by over 40%. In 1996, a large practice in Minneapolis consisting of 19 gastroenterologists analyzed the economic impact of adopting the postpolypectomy recommendations of the National Polyp Study [53]. A survey of 500 prior cases indicated that this group of physicians had deviated from these recommendations in 45% of their cases (range 15–80%); most were performing more frequent follow-up examinations than were needed. After imple- menting a practice guideline based on the National Polyp Study findings, follow-up practice in the next 500 polypectomy cases deviated by only 12% (mostly a result of physicians’ deciding against any follow-up when polyps were found in elderly or ill patients). During the next 12 months, this group documented sav- ings of more then $600 000 in facility and professional charges for colonoscopy that were directly attributable to adopting a rational evidence-based guideline for post- polypectomy surveillance. Rex and Lieberman [1] recently analyzed the feasibil- ity of performing direct colonoscopy screening in the USA. They concluded that some of the capacity currently unavailable to carry out this screening could be created by shifting resources away from unnecessary post- polypectomy surveillance to colonoscopy screening. If postpolypectomy surveillance were designed to detect only advanced adenomas, two-thirds of the colono- scopies currently being done annually for surveillance could instead be used for screening. Another important cost-saving strategy is to eliminate screening for patients who are already participating in a postpolypectomy colonoscopy surveillance program. No additional colo- rectal cancer screening of any type is needed when a patient is asymptomatic and has had normal results on surveillance colonoscopy within 3–5 years. Summary Following removal of benign adenomatous polyps, there is a 30–50% likelihood of developing a metachron- ous adenoma in the future. Removal of colon polyps will, to a large extent, interrupt the adenoma–carcinoma sequence and protect the patient from developing car- cinoma. Not all patients have the same likelihood of developing metachronous adenomas. The timing of follow-up colonoscopic examinations needs to take into account each patient’s risk for developing metachron- ous advanced adenomas and tailor postpolypectomy surveillance strategies accordingly. Patients with colo- rectal adenomas should be stratified into high- and low-risk groups. Interval colonoscopic examination is 466 Section 10: Malignant Polyp, Post-Polypectomy & Post-Cancer Surveillance recommended in 3 years for patients who are at high risk. These high-risk patients are those who have had the removal of large or multiple adenomas, an adenoma with the advanced pathologic features of villous change, high-grade dysplasia, or invasive carcinoma, and those aged over 60 years with a parent with colorectal cancer. Patients with a low risk of metachronous advanced adenomas can safely have their first follow-up colo- noscopy at 5 years. This group of low-risk patients includes those who initially have only one or two small tubular adenomas without high-grade dysplasia or can- cer and no significant family history of colorectal can- cer. Stratification of patients into various colonoscopic follow-up strategies will permit the medical profession to conserve precious resources while providing the best and most efficient protection against the possibility of developing colon cancer. References 1 Rex DA, Lieberman DA. Feasibility of colonoscopy screen- ing: discussion of issues and recommendations regarding implementation. Gastrointest Endosc 2001; 54: 662–7. 2 Lieberman DA, De Garmo PL, Fleischer DE et al. Patterns of endoscopy use in the United States. Gastroenterology 2000; 118: 619–24. 3 Bond JH. Clinical evidence for the adenoma–carcinoma sequence, and the management of patients with colorectal adenomas. Semin Gastrointest Dis 2000; 11: 176–84. 4 Winawer SJ, O’Brien M, Waye JD et al. Risk and surveillance of individuals with colorectal polyps. Bull WHO 1990; 68: 789–95. 5 Hogan WJ, Stewart ET, Geenen JE et al. A prospective com- parison of the accuracy of colonoscopy vs. air-contrast bar- ium enema for detection of colonic polypoid lesions (abstract). Gastrointest Endosc 1977; 23: 230. 6 Winawer SJ, Stewart ET, Zauber AG et al. A comparison of colonoscopy and double-contrast barium enema for surveil- lance after polypectomy. N Engl J Med 2000; 342: 1766– 72. 7 Rex DK, Rahmani EY, Haseman JH et al. Relative sensitivity of colonoscopy and barium enema for detection of colorectal cancer in clinical practice. Gastroenterology 1997; 112: 17–23. 8 Schrock TR. Colonoscopy versus barium enema in the dia- gnosis of colorectal cancer and polyps. Gastrointest Endosc Clin North Am 1993; 3: 585–610. 9 Fenlon HM, Nunes DP, Schroy PC 3rd et al. A comparison of virtual and conventional colonoscopy for the detection of colorectal polyps. N Engl J Med 1999; 341: 1496–503. 10 Fletcher JG, Johnson CD, Welch TJ et al. Optimization of CT colonography technique: prospective trial in 180 patients. Radiology 2000; 216: 704–11. 11 Yee J, Akerkar GA, Hung RK et al. Colorectal neoplasia: per- formance characteristics of CT colonography for detection in 300 patients. Radiology 2001; 219: 685–92. 12 Cotton PB, Durkalski VL, Yuko YP et al. Comparison of virtual colonoscopy and colonoscopy in the detection of polyps/masses (abstract). Gastrointest Endosc 2002; 55: A98. 13 Spencer RJ, Melton LJ III, Ready RL et al. Treatment of small colorectal polyps: a population-based study of risk of subse- quent carcinoma. Mayo Clin Proc 1984; 59: 305–10. 14 Lotfi AM, Spencer RJ, Illstrup DM et al. Colorectal polyps and the risk of subsequent carcinoma. Mayo Clin Proc 1986; 61: 337–43. 15 Atkin WS, Morson BC, Cuzick J. Long-term risk of colo- rectal cancer after excision of rectosigmoid adenomas. N Engl J Med 1992; 326: 658–62. 16 Grossman S, Milos ML, Tdekawa IS, Jewell NP. Colono- scopic screening of persons with suspected risk factors for colon cancer: past history of colorectal neoplasms. Gastro- enterology 1989; 96: 299–306. 17 Bond JH. Clinical relevance of the small colonic polyp. Endoscopy 2001; 33: 454–7. 18 Fearon ER. Molecular genetic studies of the adenoma– carcinoma sequence. Adv Intern Med 1994; 39: 123–47. 19 Winawer SH, Zauber AG, O’Brien MJ et al. The National Polyp Study: design, methods, and characteristics of patients with newly diagnosed polyps. Cancer 1992; 70 (Suppl.): 1236–45. 20 Hoff G, Foerster A, Vatn MH et al. Epidemiology of polyps in the rectum and colon: recovery and evaluation of unre- sected polyps 2 years after detection. Scand J Gastroenterol 1986; 21: 853–62. 21 Obata M, Fukami N, Shin-Ei Kudo, Kanagawa N. Serial colonoscopic follow-up of small colorectal polyps over years (abstract). Gastroenterology 2002; 122: A621. 22 Eide T. Risk of colorectal cancer in adenoma-bearing indi- viduals within a defined population. Int J Cancer 1986; 38: 173–6. 23 O’Brien MJ, Winawer SJ, Zauber AG et al. The National Polyp Study: patient and polyp characteristics associated with high-grade dysplasia in colorectal adenomas. Gastro- enterology 1990; 98: 371–9. 24 Fenoglio CM, Pascal RR. Colorectal adenomas and cancer: pathologic relationships. Cancer 1982; 50: 2601–8. 25 Stryker SS, Wolff BG, Culp CE et al. Natural history of untreated colonic polyps. Gastroenterology 1987; 93: 1009– 13. 26 Rex D. Colonoscopy: a review of its yield for cancer and adenomas by indication. Am J Gastroenterol 1995; 90: 353– 65. 27 Hixson LJ, Fennerty MB, Sampliner RE et al. Prospective blinded trial of the colonoscopic miss-rate of large colorectal polyps. Gastrointest Endosc 1991; 37: 125–7. 28 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. 29 Hixson LJ, Fennerty MB, Sampliner RE et al. Two-year incid- ence of colon adenomas developing after tandem colono- scopy. Am J Gastroenterol 1994; 89: 687–91. 30 Benson S, Mott LA, Dain B et al. The colonoscopic miss rate and true one-year recurrence of colorectal neoplastic polyps. Am J Gastroenterol 1999; 94: 194–9. 31 Winawer SJ, Ritchie MT, Diaz B et al. The National Polyp Study: aims and organization. Front Gastrointest Res 1986; 10: 216–25. 32 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 1993; 328: 901–6. 33 Bond JH. Endoscopic therapy for the polyp with cancer and the large polyp. Pract Gastroenterol 1994; 18: 18C–18I. 34 Gilbertsen VA, Nelms JM. The prevention of invasive can- cer of the rectum. Cancer 1978; 41: 1137–9. Chapter 39: Postpolypectomy Surveillance 467 35 Selby JV, Friedman GD, Quesenberry CP et al. A case- control study of screening sigmoidoscopy and mortality from colorectal cancer. N Engl J Med 1992; 326: 653–7. 36 Newcomb PA, Norfleet RG, Storer BE et al. Screening sig- moidoscopy and colorectal cancer mortality. J Natl Cancer Inst 1992; 84: 1572–5. 37 Muller AD, Sonnenberg A. Prevention of colorectal cancer by flexible endoscopy and polypectomy: a case-control study of 32 702 veterans. Ann Intern Med 1995, 123: 904– 10. 38 Winawer SJ, Zauber AG, Ho MN et al. Prevention of colorec- tal cancer by colonoscopic polypectomy. N Engl J Med 1993; 329: 1977–83. 39 Thiis-Evensen E, Hoff GS, Sauar J et al. Population-based surveillance by colonoscopy: effect on the incidence of colo- rectal cancer. Telemark Polyp Study I. Scand J Gastroenterol 1999; 34: 414–20. 40 Citarda F, Tomaselli G, Capocaccia R et al. Efficacy in stand- ard clinical practice of colonoscopic polypectomy in reduc- ing colorectal cancer incidence. Gut 2001; 48: 812–15. 41 Zauber AG, Winawer SJ, Loeve F et al. Effect of initial polypectomy versus surveillance polypectomy on colorec- tal cancer incidence reduction: micro-simulation modeling of National Polyp Study data (abstract). Gastroenterology 2000; 118: A187. 42 Muto T, Bussy HJR, Morson BC. The evolution of cancer of the colon and rectum. Cancer 1975; 36: 2251–70. 43 Winawer SJ, Zauber A for the National Polyp Study Workgroup. The National Polyp Study: temporal sequence of evolving colorectal cancer from the normal colon (abstract). Gastrointest Endosc 1987; 33: 167. 44 Winawer SJ. Appropriate intervals for surveillance. Gastro- intest Endosc 1999; 49: S63–S66. 45 Zauber AG, Winawer SJ. Initial management and follow-up of patients with colorectal adenomas. Gastroenterol Clin North Am 1997; 26: 85–101. 46 Van Stolk RU, Beck GJ, Baron JA et al. Adenoma character- istics at first colonoscopy as predictors of adenoma recur- rence and characteristics at follow-up. Gastroenterology 1998; 115: 13–18. 47 Kairasp C, Noshirwani MD, van Stolk RU et al. Adenoma size and number are predictive of adenoma recurrence: im- plications for surveillance colonoscopy. Gastrointest Endosc 2000; 51: 422–7. 48 Mysliwiec PA, Pfeiffer R, Lanza E, Schatzkin A. Character- istics of baseline colorectal adenomas as predictors of aden- oma recurrence (abstract). Gastroenterology 2002; 122: A570. 49 Winawer SJ, Fletcher RH, Miller L et al. Colorectal cancer screening: clinical guidelines and rationale. Gastroenterology 1997; 112: 594–642. 50 Bond JH for the Practice Parameters Committee of the American College of Gastroenterology. Polyp guideline: diagnosis, treatment, and surveillance for patients with colorectal polyps. Am J Gastroenterol 2000; 95: 3053–63. 51 Ransohoff DF, Lang CA, Kuo HS. Colonoscopic surveil- lance after polypectomy: considerations of cost effective- ness. Ann Intern Med 1991; 114: 177–82. 52 Lieberman DA. Cost-effectiveness model for colon cancer screening. Gastroenterology 1995; 109: 1781–90. 53 Allen JI. Rational management of colorectal polyps: how to prevent colorectal cancer yet keep the health care system solvent. Med J Allina 1996; 5: 16–20. was 3.2% of all patients operated upon for colon cancer. Because of the low incidence of recurrent cancer of the anastomosis, the conclusion was that colonoscopy was not the procedure of choice for the follow-up search for recurrent cancer. This is also reflected in Chapter 11, con- cerning colonoscopy and the incidence of anastomotic cancer and metachronous adenomas (Figs 40.3, 40.4) fol- lowing colon cancer resection. The data in this chapter (Table 40.3) reports a combined 7.6% incidence of recur- rent cancer at the anastomosis and metachronous cancer at other sites. As for the frequency of follow-up examinations, there was little difference in any of the studies between recurrent colon cancer in patients who had an intensive follow-up after curative surgery versus those whose follow-up was “conventional” as a control population [1]. During follow-up examinations, metachronous can- cers were relatively low in prevalence (Tables 40.2, 40.3). The overall rate of detection of metachronous carcinoma in the Renahan et al. review was 1.3% [2]. Overall, the rate of recurrent cancer between patients that are followed with “intensive” follow-up regimens versus a control group showed no difference, with a 33% recurrence rate in the intensive group and 33% in those having regular follow-up examinations. However, it may be important that recurrences were detected 8.5 months earlier in the group that had intensive follow- up examinations. The intensive follow-up regimens often consisted of clinic visits and tests every 3 months for 2 years then every 6 months. These tests usually included liver function studies, complete blood count, chest X-ray, carcinoembryonic antigen (CEA) levels, and liver ultrasound every 6 months, CT scan every year, colonoscopy at intervals of 6 months for 3 years and then less frequent. The control groups had less frequent examinations. Even with “intensive” follow-up, the symptomato- logy of the patient is an important parameter in herald- ing the recurrence of colonic cancer. In spite of intensive surveillance, symptoms will be the first sign of tumor recurrence in 27–50% of patients who have recurrence of colon cancer [24]. Of all of the tests that can be per- formed for the follow-up of patients after curative resec- tion for colon cancer, Kievit [25], in an extensive literature 468 Introduction After curative operative resection for colon cancer, colonoscopy follow-up examinations are frequently performed with the intention of detecting recurrence of cancer, and to remove new adenomas in the attempt to prevent metachronous cancers from developing [1] (Table 40.1). The most important question to be ad- dressed is whether interval repeat colonoscopy follow- ing colon cancer resection will indeed detect recurrence of colon cancer at a stage when a salvage operation can be successfully performed, and if so, what should be the optimum time for the colon examination. A second question is: can colonoscopy prevent metachronous car- cinomas, and if so, at what intervals should follow-up colonoscopy be performed? In order to answer the first question, it is necessary to assess the probability of an intraluminal recurrence of cancer at the suture line (Fig. 40.1). As reported in a sys- tematic review and metaanalysis of randomized con- trolled trials and follow-up, intraluminal recurrence of cancer at the anastomosis (Fig. 40.2) accounts for only a small percentage of patients who develop recurrent carcinomas [2] (Table 40.2). Makela et al. [3] found intra- luminal recurrences in only 3 of 106 patients who had tumor recurrence following surgical resection, while Ohlsson et al. [4] reported four anastomotic recurrences in 107 patients. Schoemaker et al. [5] discovered eight intraluminal recurrences out of 325 patients with recur- rent cancers, and Pietra et al. [6] reported only two intra- luminal recurrences out of 207 patients with recurrent tumor previously operated upon for colorectal cancer. Kjeldsen et al. [7], on the other hand, reported that 16 out of 283 patients with recurrent cancer were found to have intraluminal recurrences. The overall rate of reported intraluminal recurrences in the Renahan et al. review [2] Chapter 40 Colonoscopy after Colon Cancer Resection F.P. Rossini and J.D. Waye Table 40.1 Aims of colonoscopic surveillance after resection for colorectal cancer. 1 Detect synchronous neoplasia 2 Diagnose and treat metachronous neoplasia 3 Evaluate the anastomosis Colonoscopy Principles and Practice Edited by Jerome D. Waye, Douglas K. Rex, Christopher B. Williams Copyright © 2003 Blackwell Publishing Ltd [...]... Colonoscopy, Early Colorectal Cancer, and Flat Adenomas Table 41.3 Pit pattern of colorectal neoplasms and histology 481 Adenoma Pit pattern type Low-grade High-grade IIIs 202 88 .6% 783 2 95.7% 1473 76.6% 127 17 IIIL IV I Total 9 3.9% 0 0% 73 3 .8% 67 354 376 145 V Submucosal cancer (T1) 2 28 8 186 1922 339 62.5% N Total accuracy of pit pattern analysis is 95.5% for differentiating between neoplastic and. .. were randomized to no follow-up or intensive follow-up after surgery and early postoperative colonoscopy These authors found no increased survival attributed to intensive follow-up after resection for colorectal cancer In 19 98, Schoemaker et al [5] reported that of 325 patients who underwent curative resection for colon cancer and were randomized into intensive or standard follow-up, yearly colonoscopy. .. Method of examination Flat and depressed lesions Hunt & Cherian [14] Australia Case reports of flat carcinoma of the colon Videocolonoscopy 3 cases Wolber & Owen [15] Canada Surgical pathology specimens between 1 988 and 1 989 ( 18 months); excluded UC and FAP Histopathology of resected specimens 8. 6% Lanspa et al [16] USA Routine colonoscopy for various indications (n = 1 48) Videocolonoscopy 12% Jaramillo... dye-assisted colonoscopy between June 1, 19 98 and February 28, 1999 [20] Patients with inflammatory bowel disease and polyposis syndrome were excluded A total of 2 98 polypoid lesions were detected After excluding 110 lesions that were hyperplastic polyps, the remaining 188 lesions excised (from 102 patients) comprised 66 lesions of the flat and depressed type and 122 with a polypoid appearance Flat and. .. nonneoplastic, and are seldom removed Once this pattern is identified, the overall Table 41.2 Gross appearance of colorectal neoplasm and pit pattern Pit pattern type V Appearance of colorectal neoplasm Depressed Flat elevated Protruded Total IIIL 62 IV IIIs 1 3944 299 88 .2% 6.7% (94 .8% ) 5926 187 2 73.2% 23.1% (96.3%) 9953 2172 I N 234 54.4% 16 3.7% (85 .3%) 117 117 27.2% 58 Total 430 100% 56 4474 100% 8 2 28 66 81 00... and regular in both size and arrangement The pits of hyperplastic polyps (type II) are larger than normal pits, and instead of round, are star or onion-like, but are regularly arranged Types I and II pit patterns are characteristic of nonneoplastic lesions Diameter of lesion (mm) < 10 11–20 > 21 Total 64/343 3/ 682 0 41 /87 54 18. 7% 0.04% 0.5% 51/73 19/614 115/1 183 69.9% 3.1% 9.7% 12/14 48/ 199 50/165 85 .7%... 68 74 710 135 237 97 240 132 6 NC 38 19 15 290 307 2 4 10 NS NS 3 .8 7.4 2.7 13 35 34 97 1 17.5 304 11.6 6.1 21.3 11.4 20% 25% NS NS 3.3% (5 out of 13 diagnosed by colonoscopy) 1 .8% (3 out of 10 diagnosed by colonoscopy) 1 .8% 4% 14.5% 21% 17% 7.6% 17.2% 103 104 1 58 154 167 577 56 75 56 197 36 98 20% * Number of patients with given findings at one or more examination NC, not clear; NS, not stated with colonoscopy, ... communication Follow-up 4 years Prospective Mean follow-up 5.5 year Prospective Follow-up: conventional vs intensive Prospective Follow-up: standard vs intensive Unger & Wanebo [22] Weber [23] Prospective Prospective Total Patients (no.) Colonoscopies (no.) Cancer (anastomotic recurrence and metachronous)* (%) Adenoma* (%) 52 207 445 2 7 17 NC 51 129 51 3 58 3.9 0 .8 40 33 66 284 66 284 3 3.3 4.5 19.1... Jorgensen OD A prospective randomized study of follow-up after radical surgery for colorectal cancer Br J Surg 1997; 84 : 666 –9 Berkowitz I, Kaplan M Indications for colonoscopy An analysis based on indications and diagnostic yield S Afr Med J 1993; 83 : 245 8 Brady PG, Straker RJ, Goldschmid S Surveillance colonoscopy after resection for colon carcinoma South Med J 1990; 83 : 765 8 Brenna E, Skreden K, Waldum... were generally seen in patients over 60 years of age ( 78% ) but not in patients under 40 years of age and were twice as common in men than women Most (71%) were 0.5 cm or less, 21% were 0.6–1.0 cm, and 8% were more than 1.0 cm Low-grade dysplasia was seen in 86 % and high- Kiesslich and colleagues [21] studied 100 consecutive patients during routine colonoscopy using vital staining with indigocarmine solution . undergoing post- polypectomy surveillance [6]. A total of 86 2 back-to-back double-contrast barium enema examinations and colo- noscopies were performed in 680 patients. Expert radio- logists or. Cancer of the Colon Chapter 41 Magnifying Colonoscopy, Early Colorectal Cancer, and Flat Adenomas Hiroshi Kashida and Shin-ei Kudo Colonoscopy Principles and Practice Edited by Jerome D. Waye, Douglas. mm) and medium-sized (6–9 mm) polyps of 16 and 12% respectively; however, no large polyps (≥ 1 cm) went undetected. A similarly designed tandem colonoscopy study by Rex and colleagues [ 28] reported