Malignancy in ulcerative colitis (UC) is believed to ORIGINAL ARTICLES

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1 CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2004;2: ORIGINAL ARTICLES Long-term Follow-up After Polypectomy Treatment for Adenoma-Like Dysplastic Lesions in Ulcerative Colitis ROBERT D. ODZE,* FRANCIS A. FARRAYE, JONATHAN L. HECHT, and JASON L. HORNICK* *Department of Pathology, Brigham and Women s Hospital, Boston; Department of Pathology, Beth Israel Deaconess Medical Center, Boston; and Section of Gastroenterology, Boston Medical Center, Boston, Massachusetts Background & Aims: A previously published study by our group suggested that adenoma-like dysplasia-associated lesions or masses (DALMs) in ulcerative colitis (UC) may be treated adequately by polypectomy and continued endoscopic surveillance. The length of follow-up evaluation in these patients averaged only 42 months. The purpose of this study was to evaluate the long-term outcome of our previously defined group of UC patients, all with adenoma-like DALMs, who were treated by polypectomy. Methods: The clinical, endoscopic, and pathologic outcome of 34 UC patients, 24 with an adenoma-like DALM, and 10 with a coincidental sporadic adenoma, 28 of whom were treated by polypectomy and continued endoscopic surveillance, and 6 by colonic resection, were compared with the outcome of 49 non-uc patients who were treated similarly for a sporadic adenoma. The mean length of follow-up evaluation averaged 82.1 months and 71.8 months for the 2 UC subgroups, respectively, and 60.4 months for the non-uc controls. Results: Overall, 20 of 34 UC patients (58.8%) developed at least one further adenoma-like DALM on follow-up evaluation. One patient had flat low-grade dysplasia present in the colon, which was resected within 6 months of the initial polypectomy, and another patient, with primary sclerosing cholangitis, developed adenocarcinoma 7.5 years after her initial polypectomy. There was no significant difference in the prevalence of polyp formation on follow-up evaluation between UC patients with an adenoma-like DALM (62.5%) and UC patients with a sporadic adenoma (50%), or between either of these 2 UC patient subgroups and the non-uc sporadic adenoma patient group (49%; P > 0.05). Conclusions: UC patients who develop an adenoma-like DALM may be treated adequately by polypectomy with complete excision and continued endoscopic surveillance. Malignancy in ulcerative colitis (UC) is believed to develop through a dysplasia-carcinoma sequence. 1,2 At present, evaluation of mucosal biopsy specimens for the presence or absence of dysplasia is the most reliable and important predictor of the future risk for carcinoma in affected patients. 1,3,4 However, recent data suggest that interpretation of dysplasia is highly dependent on the gross characteristics of the dysplastic lesion. 5 8 For instance, dysplasia in UC may be flat (endoscopically undetectable) or elevated (endoscopically detectable), the latter of which is referred to as a dysplasia-associated lesion or mass (DALM). 5 At a microscopic level, UCassociated dysplasia is classified further as either low or high grade. 1,2 Traditionally, flat high-grade dysplasia generally has been considered a strong indication for colectomy because of its high association with either metachronous or synchronous adenocarcinoma. Recent data suggest that flat low-grade dysplasia also should be treated by colectomy, particularly if it is multifocal, develops in a sequential fashion, or is present at the time of the patient s initial screening or surveillance endoscopy However, the treatment of DALMs is controversial. This is primarily owing to the fact that the risk for malignancy is highly dependent on the particular gross appearance of the tumor. 5,7,8 For instance, DALMs in UC are classified broadly as either adenoma-like or non adenoma-like based on their gross endoscopic characteristics. 5,8 Adenoma-like lesions typically are well-circumscribed, sessile or pedunculated polyps that resemble adenomas in patients without UC. In contrast, non adenoma-like DALMs are broad-based, sessile, irregular, ulcerating, or constricting lesions that have a high association with metachronous or synchronous adenocarcinoma As a result, the presence of a non adenomalike DALM still is considered a strong indication for colectomy in medically fit UC patients. 6 Abbreviation used in this paper: DALM, dysplasia-associated lesion or mass by the American Gastroenterological Association /04/$30.00 PII: /S (04)00237-X

2 July 2004 ADENOMAS IN UC 535 With regard to adenoma-like DALMs, in 1999, our research group reported the outcome of 34 UC patients, all of whom had an adenoma-like DALM treated by polypectomy and continued endoscopic surveillance. 8 Fifty-eight percent of UC patients developed a further adenoma-like DALM on follow-up evaluation, which was statistically similar to a control group of non-uc patients with a sporadic adenoma. Only 1 patient developed an isolated focus of flat low-grade dysplasia, and none developed adenocarcinoma. These results were dramatically similar to those of a similar study by Rubin et al. 7 that was published at the same time. They also suggested that these patients may be treated safely, at least initially, by polypectomy and surveillance. Unfortunately, interpretation of the results of both of these studies was limited by the relatively short length of follow-up evaluation, which averaged 42 months in our previous study and approximately 49 months in the study by Rubin et al. 7 Thus, we felt that before recommending definitively that polypectomy and surveillance is adequate treatment for UC patients with an adenomalike DALM, long-term outcome would need to be determined. Therefore, the purpose of this study was to evaluate the long-term outcome of our initial cohort of 34 UC patients with an adenoma-like DALM, 28 of whom were treated conservatively by polypectomy and continued endoscopic surveillance, and 6 of whom were treated by colonic resection. The data from our UC patient group were compared with an age- and sexmatched population of non-uc patients, all of whom had a sporadic adenoma also treated by polypectomy. Materials and Methods Study Group The study group consisted of 34 UC patients, all of whom had at least one adenoma-like DALM detected during the course of endoscopic surveillance. These patients were the subjects of a previously published study by our research group. 8 They originally were chosen by a retrospective search through the pathology files of the Brigham and Women s Hospital and Beth Israel Deaconess Medical Center, Boston, MA, between 1990 and These patients were stratified into 2 subgroups for the purpose of data analysis. One group consisted of 24 patients who had an adenoma-like DALM located within an area of histologically confirmed chronic, or chronic active, colitis, and the other group consisted of 10 UC patients who had an adenoma-like DALM located outside of the most proximal extent of chronic, or chronic active, colitis. In this latter group, the DALMs were considered unrelated to the patient s UC and, thus, likely represented a sporadic adenoma. In addition, as in our original study, 49 non-uc patients, all of whom had a sporadic adenoma treated by polypectomy and continued surveillance, were used as a control group. Adenoma-like DALMs in the UC patients represented lesions that were discrete, well-circumscribed, sessile or pedunculated polyps, which resembled sporadic adenomas at endoscopy. None of the UC patients had a non adenoma-like DALM, which was defined as an irregular, elevated, broadbased, ulcerated, or strictured lesion endoscopically. Both our UC and control patients underwent endoscopic procedures that consisted of a total colonoscopy, with distal ileoscopy, using an Olympus (Olympus Co., Melville, NY) or Fuginon (Fuginon Co., Wayne, NJ) endoscope. During each endoscopy, the location and number of polyps were recorded. Of the 28 UC patients who were followed-up by endoscopic surveillance (i.e., 6 patients had a colectomy), 39% underwent at least one endoscopic surveillance procedure per year, 43% had one procedure every second year, and 18% had 1 procedure every 3 years during the course of follow-up evaluation (mean number of endoscopies, 4.4; range, 1 13). There were no differences in the frequency of follow-up surveillance endoscopies between the 2 UC subgroups. At each endoscopy, UC patients were subjected to a standardized biopsy protocol that consisted of 4-quadrant biopsies every 10 cm, in addition to sampling of all elevated, nodular, or mass-like areas. Non-UC control patients underwent less frequent endoscopies (mean number of endoscopies, 1.6; range, 1 4), according to the recommended American College of Gastroenterology guidelines for surveillance of patients with colonic adenomas. 15 Follow-up data were obtained by a review of the patients hospital charts, endoscopy reports, and endoscopically obtained photographs when available. The length of follow-up evaluation was recorded from the date of the patients initial polypectomy to either the most recent endoscopic procedure or colonic resection. This study was approved by the internal institutional review board at the Brigham and Women s Hospital and Beth Israel Deaconess Medical Center, Boston, MA. Histologic Evaluation Routinely processed, paraffin-embedded, H&E-stained tissue sections of all polypectomy samples were evaluated for their size (in mm), architectural type (tubular, tubulovillous, or villous), and degree of dysplasia (low or high grade) according to previously published criteria. 2 The presence or absence, and extent, of chronic, or chronic active, colitis and flat dysplasia also was determined by histologic evaluation of mucosal biopsy specimens from nonpolypoid mucosa according to previously published criteria. 1 The extent of colitis was categorized as total (involvement of rectum to cecum), subtotal (involvement of rectum to ascending colon or proximal or distal transverse colon), or left-sided only (rectum or rectum and sigmoid colon). For patients who had a colectomy, the colonic resection specimens were evaluated for the length and degree of colitis, the presence or absence of flat and/or polypoid dysplasia, or adenocarcinoma. All specimens were evaluated by

3 536 ODZE ET AL. CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 2, No. 7 Table 1. Clinical and Pathologic Features of UC Patients With Adenoma-Like DALMs or Sporadic Adenomas UC patients groups Non-UC patients Clinical/pathologic feature Adenoma-like DALM Sporadic adenoma Sporadic adenoma No. of patients Male/female ratio 14/10 7/3 31/18 Mean age (yr SD) 61.5 ( 17.3) 59.8 ( 15.4) 60.8 ( 10.6) Mean duration of disease (yr SD) 10.4 ( 12.0) 6.3 ( 6.0) NA Extent of disease Pancolitis 12 (50%) 0 (0%) NA Subtotal colitis 8 (33%) 6 (60%) Left-sided colitis 4 (17%) 4 (40%) No. of polyps Polyp location Left colon 18 (70%) 5 (41%) 21 (43%) Transverse colon 1 (4%) 2 (17%) 6 (12%) Right colon 5 (18%) 2 (17%) 16 (33%) Cecum 2 (8%) 3 (25%) 6 (12%) Mean polyp size (cm SD) 0.85 ( 0.7) 0.63 ( 0.2) 0.72 ( 0.3) Dysplasia Low grade 20 (76%) 7 (58%) 36 (73%) Focal high grade 3 (12%) 4 (33%) 9 (18%) Diffuse high grade 3 (12%) 1 (9%) 4 (8%) Architecture Tubular 23 (88%) 11 (91%) 40 (81%) Tubulovillous 3 (12%) 1 (9%) 6 (12%) Villous 0 (0%) 0 (0%) 3 (6%) NA, not applicable. 2 pathologists (J.L.H. and R.D.O.) with no interobserver variability in interpretation. Statistical Evaluation The data were evaluated using the stat V.S.O. software program (Stata, College Station, TX). Comparisons between the different study groups and controls regarding discrete variables were evaluated using the Fisher exact test and 2 analysis, where appropriate. A P value of 0.05 was considered statistically significant. Results Clinical and Pathologic Characteristics A summary of the clinical and pathologic features of the UC and control patients is presented in Table 1. Table 1 was reproduced from our previously published report that used the same cohort of UC patients and controls. Overall, the 34 UC patients and the 49 non-uc control patients showed a statistically similar distribution of polyps, mean polyp size, prevalence of high-grade dysplasia, and prevalence of a villous, or tubulovillous, growth pattern. Of the 34 UC patients, 12 (35%), 14 (41%), and 8 (24%) had microscopically confirmed pancolitis, subtotal colitis, or limited left-sided colitis, respectively, at the time of initial polypectomy. The mean duration of disease was 9.2 years ( 8.4 yr). Twenty-four patients had an adenoma-like DALM (26 polyps in total) present within an area of previously microscopically confirmed colitis, whereas 10 had polyps (12 polyps in total) located proximal to an area of colitis and, therefore, were considered sporadic adenomas. Furthermore, there were no significant differences with regard to male/female ratio, mean age, mean duration of disease, polyp location or size, the degree of dysplasia, or type of growth pattern between the 2 UC patient subgroups. Interestingly, 3 of the 24 UC patients with an adenoma-like DALM were under the age of 40. However, their outcome was similar to that of patients greater than 40 years of age. Two of the 3 patients developed a further adenoma-like DALM on follow-up evaluation, but none developed flat dysplasia. Follow-up Results UC patients with an adenoma-like DALM. Of the 24 UC patients with an adenoma-like DALM, 6 had a total colectomy within 6 months of their initial endoscopic polypectomy procedure because of their DALM. Of the 6 patients, 1 patient had an isolated focus of low-grade dysplasia present in their resection specimen, but none of the other resected patients had evidence of either flat dysplasia or adenocarcinoma. Three patients did not have any other polyps present in their colectomy

4 July 2004 ADENOMAS IN UC 537 Table 2. Follow-up Data of UC Patients With Adenoma-Like DALMs or Sporadic Adenomas UC patients groups Non-UC patients Clinical/pathologic feature Adenoma-like DALM Sporadic adenoma Sporadic adenoma No. of patients No. with colectomy No. with endoscopic surveillance Mean follow-up of patients who had endoscopic 82.1 (17 156) 71.8 (7 135) 60.4 (29 100) surveillance, mo (range) Mean no. of colonoscopies (range) 5.4 (2 13) 5.6 (3 11) 2.2 (2 4) No. of patients who developed new polyps 15 (62.5%) 5 (50%) 24 (49%) No. of polyps/patient at colectomy or on endoscopic follow-up examination 0 9 (38%) 5 (50%) 25 (51%) 1 7 (29%) 4 (40%) 15 (31%) 2 5 (21%) 1 (10%) 4 (8%) 3 2 (8%) 0 (0%) 4 (8%) 4 0 (0%) 0 (0%) 1 (2%) 5 1 (4%) 0 (0%) 0 (0%) Polyp location Left colon 19 (68%) 2 (33%) 15 (38%) Transverse colon 2 (7%) 0 (0%) 6 (15%) Right colon 5 (18%) 2 (33%) 9 (23%) Cecum 2 (7%) 2 (33%) 9 (23%) Within colitis 26 (93%) 0 (0%) NA Proximal to colitis 2 (7%) 6 (100%) NA Mean polyp size, cm (range) 0.73 ( ) 0.43 ( ) 0.58 ( ) Dysplasia Low grade 25 (89%) 4 (67%) 29 (74%) Focal high grade 3 (11%) 2 (33%) 8 (21%) Diffuse high grade 0 (0%) 0 (0%) 2 (5%) Architecture Tubular 22 (79%) 5 (83%) 33 (85%) Tubulovillous 6 (21%) 1 (17%) 4 (10%) Villous 0 (0%) 0 (0%) 2 (5%) No. of patients who had or developed flat dysplasia a 1 (4%) 0 (0%) NA No. of patients who had or developed 1 (4%) 0 (0%) 0 (0%) adenocarcinoma NA, not applicable. a One patient had dysplasia in the colectomy specimen; none developed dysplasia on endoscopic surveillance. specimen, whereas 2 patients had 1 adenoma-like DALM, and 1 patient had 2 adenoma-like lesions present in their resection specimens. All 4 polyps, from all 3 patients, were isolated, well-circumscribed, adenomalike lesions that occurred within an area of established chronic colitis, and all were similar in appearance to the initial polyp that was removed by polypectomy. The other 18 patients had an initial polypectomy followed by endoscopic surveillance, with a mean follow-up period of 82.1 months (range, mo). These patients had a mean of 4.4 colonoscopies per patient (range, 1 13 colonoscopies). Of these 18 patients under surveillance, 10 (56%) were followed-up for more than 7 years (84 mo), of which 7 (39%) were followed-up for more than 8 years. A summary of the findings at colectomy (6 patients) and the endoscopic follow-up data for all the other UC and control patients under surveillance is outlined in Table 2. In addition, Figure 1A C shows a summary of the sequence of polyp formation, and outcome, of the 2 UC patient subgroups, and the control group who were followed-up by endoscopic surveillance. Of the 24 UC patients with an adenoma-like DALM, 9 (38%) did not have (at colectomy) or develop (on surveillance) any further polyps, whereas 7 (29%) had 1, 5 (21%) had 2, 2 (8%) had 3, and 1 patient (4%) had 5 adenoma-like DALMs detected on follow-up examination. Thus, in total, 15 of 24 (62.5%) patients had 1 further adenoma-like DALMs identified on follow-up endoscopic examination or at colectomy. The distribution, size, degree of dysplasia, and architectural type of the polyps identified on follow-up examination are summarized further in Table 2. None of the patients in this group followed-up by endoscopic surveillance (18 in total) de-

5 538 ODZE ET AL. CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 2, No. 7 Figure 1. Outcome of UC patients with (A) an adenoma-like DALM or (B) a sporadic adenoma treated by colectomy or polypectomy and endoscopic surveillance. (C) Outcome of the non-uc (control) patients with a sporadic adenoma also treated by polypectomy and endoscopic surveillance. In all 3 parts, outcome 1 represents the follow-up results from our previously published study, whereas outcome 2 represents the new long-term follow-up results of the present study. lost to F/U, lost to follow-up evaluation. veloped flat dysplasia, and only 1 patient developed a poorly differentiated adenocarcinoma of the cecum. This patient (a 74-year-old woman with a 9-year history of pancolitis) also had primary sclerosing cholangitis and was 5 years status post liver transplant. Interestingly, the adenocarcinoma was detected 7.5 years after the patient s initial polypectomy. In fact, 3 intervening colonoscopic examinations failed to identify any polyps or evidence of adenocarcinoma. Because of other medical reasons, and contrary to the standard practice for UC patients with primary sclerosing cholangitis in which yearly colonoscopic surveillance evaluations are recommended, this patient s most recent colonoscopy was performed 3 years before the diagnosis of adenocarcinoma. UC patients with a sporadic adenoma. None of these patients had a colectomy. All 10 patients were followed-up by endoscopic surveillance for a mean of 71.8 months (range, mo). In fact, 4 of the 10 patients (40%) were followed-up for more than 7 years, of which 3 (30%) actually were followed-up for more than 8 years. Of the 10 UC patients with a sporadic adenoma initially treated by polypectomy and continued endoscopic surveillance, 5 (50%) did not develop any further polyps, whereas 4 (40%) and 1 patient (10%) developed 1 and 2 further sporadic adenomas, respectively, on follow-up examination. Thus, overall, 5 of 10 patients (50%) developed 1 further sporadic adenomas on follow-up examination. All of the polyps identified on follow-up examination were located proximal to areas of colitis and, thus, also were considered definite sporadic adenomas. None of these patients (0%) developed either flat dysplasia or adenocarcinoma. No significant differences were observed with regard to the prevalence of polyp formation, the mean polyp size, degree of dysplasia, architectural type, or development of flat dysplasia or adenocarcinoma between the UC patients with an adenoma-like DALM compared with those with a sporadic adenoma. Non-UC (control) patients with a sporadic adenoma. None of these patients had a colectomy. The mean follow-up time for this group of patients, all of whom were followed-up by endoscopic surveillance, was 60.4 months (range, mo). In this group, 10 patients (20%) were followed-up for more than 7 years, of which 3 (6%) were followed-up for more than 8 years. Of the 49 non-uc control patients with a sporadic adenoma, 25 (51%) did not develop any further polyps. However, 15 (31%) developed 1, 4 (8%) developed 2, 4 (8%) developed 3, and 1 (2%) developed 4 further sporadic adenomas on follow-up evaluation. Thus, in total, 24 of 49 (49%) control patients developed 1 further sporadic adenomas on follow-up evaluation. This value was not statistically different from the UC patients in total, or in comparison with each of the 2 individual UC subgroups. Furthermore, there were no differences with regard to polyp location, mean polyp size, degree of dysplasia, or architectural type compared with the UC patients. Finally, none of the control patients with sporadic adenomas developed adenocarcinoma. Discussion DALMs are a heterogeneous group of lesions that have varying endoscopic and morphologic features. 5,6 Recently, we proposed a clinically useful classification of DALMs into 2 broad groups (adenoma-like and non adenoma-like), which is based on their gross (endoscopic) appearance. 5 The main clinical difference between these

6 July 2004 ADENOMAS IN UC groups relates to their different risk for malignancy. It is well known that non adenoma-like DALMs have up to an 80% risk for either metachronous or synchronous occurrence of adenocarcinoma and, thus, is the rationale why patients with these lesions are best treated by a colectomy. 6,12 14 However, the management of adenomalike DALMs is more controversial. The controversy relates to the fact that adenoma-like lesions in UC may represent either sporadic adenomas that occur coincidentally in patients with inflammatory bowel disease, or adenoma-like polypoid areas of dysplasia that arise as a result of the underlying inflammatory disorder. Under normal circumstances the former type of lesion usually is treated by polypectomy, whereas the latter usually is treated by colectomy. The purpose of the present study was to determine the long-term outcome of a well-defined group of UC patients with an adenoma-like DALM present either within, or outside, areas of established colitis, most of whom were treated by endoscopic polypectomy and continued endoscopic surveillance. This series represents an extension of a previously reported study by our research group in which the same group of patients were followed-up for a relatively short period of time ( 42 mo). 8 The results of this long-term follow-up study showed that, overall, 59% of UC patients develop at least one further adenoma-like DALM on follow-up examination. Only one patient had an isolated focus of low-grade dysplasia present in their resection specimen. However, of the patients who were under surveillance, none developed flat dysplasia, and only one developed an adenocarcinoma, which we felt probably was unrelated to the patient s previous polyp, even though it was more than likely a colitis-induced cancer. Furthermore, the prevalence of polyp formation and the development of dysplasia or adenocarcinoma were statistically similar in UC patients regardless of whether the adenoma-like polyps occurred within or outside areas of histologically confirmed colitis. Most importantly, the prevalence of adenoma-like polyp formation in the UC patients was similar to that of a non-uc control group with sporadic adenomas who were treated by polypectomy and regular endoscopic surveillance. Based on these results, we now feel confident in suggesting that UC patients with an adenoma-like DALM have little risk for future development of dysplasia or adenocarcinoma and, as such, can be treated safely by complete polypectomy and endoscopic surveillance. Of course, this recommendation relies on the endoscopist s interpretation of the gross appearance of the lesion. One interesting aspect of this study was the fact that the outcome was similar in patients who had an adenoma-like DALM within, vs. those who had polyps located outside, areas of colitis. It is widely believed that carcinogenesis in UC occurs only within histologically inflamed areas, through an inflammation-dysplasia-carcinoma pathway. 6 Thus, adenoma-like lesions that occur proximal to areas of colitis may be accepted confidently as representing sporadic adenomas. Our data provide support for the theory that most adenoma-like DALMs that occur within areas of colitis may, in fact, also represent sporadic adenomas. In fact, there is immunohistochemical and molecular data to support this hypothesis For instance, in a molecular study by our research group that evaluated loss of heterozygosity of 3p, adenomatous polyposis coli, and p16 in UC-associated adenoma-like and non adenoma-like DALMs, and in non UC-associated sporadic adenomas, the UC-associated adenoma-like DALMs and non UC-associated sporadic adenomas showed a similar low frequency of loss of heterozygosity of these 3 genes. 17 However, non adenoma-like DALMs showed a different molecular profile. For instance, a significantly higher proportion of non adenoma-like DALMs in UC were positive for loss of heterozygosity of 3p. Only a few previous studies evaluated the outcome of well-defined adenoma-like polyps in UC. 4,7,8,20,21 In the previous study by our research group, using the same 34 UC patients, our initial results showed that the 24 UC patients with an adenoma-like DALM and the 10 UC patients with a sporadic adenoma developed further polyps at a rate of 58% and 50%, respectively, for the 2 groups. 8 These values were statistically similar to the non-uc control group in which 39% of patients developed further adenomas. However, as mentioned earlier, the mean follow-up time for the 2 UC patient groups was only 42.4 and 41.2 months, respectively, and 37 months for the non-uc control group. In our present long-term study, aside from the 1 patient who had flat low-grade dysplasia in the colectomy specimen, no other patients developed dysplasia after a mean follow-up period of 82.1 months for the adenoma-like DALM group. A study by Rubin et al. 7 showed similar results. In their series, 70 polyps from 48 patients with chronic colitis were treated by polypectomy and endoscopic follow-up evaluation. Overall, 48% of patients developed additional polyps, but none developed either flat dysplasia or adenocarcinoma after a mean follow-up period of 4.1 years. However, in contrast to our previous and present

7 540 ODZE ET AL. CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 2, No. 7 study, some of the patients had Crohn s colitis instead of UC, and a control group of non-uc patients with sporadic adenomas was not used. Several other individual case reports, or small series, with follow-up evaluations also support these findings. 20 Thus, based on these previous, as well as our present long-term, studies, we recommend that UC patients with an adenoma-like DALM may be treated adequately by polypectomy and continued endoscopic surveillance. Based on the extremely low frequency of dysplasia or adenocarcinoma on long-term follow-up evaluation, it may be possible to lengthen the interval of surveillance endoscopy to that used for UC patients who do not have dysplasia. Additional confirmatory studies are needed before definitive recommendations regarding the surveillance interval after polypectomy can be made. One of the patients in our present study ultimately developed an adenocarcinoma 7.5 years after polypectomy for an adenoma-like DALM. Although this cancer likely was colitis-induced, we do not feel that the tumor was related to the patient s previously identified adenoma-like DALM because 3 intervening colonoscopy procedures did not reveal any evidence of flat or polypoid dysplasia in the anatomic area of the previous polypectomy. Furthermore, this patient also had primary sclerosing cholangitis, which is felt to be a strong risk factor for the development of adenocarcinoma in UC. 22,23 For instance, in a study by Marchesa et al. 22 in 1997, 60% of 27 patients with UC and primary sclerosing cholangitis developed dysplasia in comparison with only 12% of 1185 UC patients without primary sclerosing cholangitis. Other studies have confirmed the high risk for dysplasia or malignancy in UC patients with primary sclerosing cholangitis. 23 In fact, although unlikely, it is also possible that this UC patient developed a sporadic colon cancer that was unrelated to the underlying inflammatory disease. The absence of either flat or polypoid dysplasia elsewhere in the colon of this patient is evidence in favor of this theory. Previous studies have shown that up to 90% of UC patients who develop a malignancy as a result of the underlying inflammatory disease show morphologic features of dysplasia either adjacent to, or distant from, the adenocarcinoma. 2,24,25 In summary, based on the results of this long-term follow-up study, we recommend that UC patients with an adenoma-like DALM may be treated by complete polypectomy and continued regular endoscopic surveillance if there is no other evidence of dysplasia in the colon. However, it is important to remember that this recommendation applies only to UC patients with an endoscopically apparent adenoma-like DALM, and does not apply to UC patients with either flat dysplasia or to those with a non adenoma-like DALM. This distinction should be made at the time of endoscopy and pathologists should not be relied on to make the distinction between an inflammatory bowel disease related and non inflammatory bowel disease related lesion. References 1. Goldman H. Significance and detection of dysplasia in chronic colitis. Cancer 1996;78: Riddell RH, Golman, Ransohoff DF, et al. Dysplasia in inflammatory bowel disease: standardized classification with provisional clinical applications. Hum Pathol 1983;14: Bansal P, Sonnenberg A. Risk factors of colorectal cancer in inflammatory bowel disease. Am J Gastroenterol 1996;91: Connell WR, Lennard-Jones JE, Williams CB, Talbot IC, Price AB, Wilkinson KH. Factors affecting the outcome of endoscopic surveillance for cancer in ulcerative colitis. Gastroenterology 1994; 107: Odze RD. Adenomas and adenoma-like DALMS in chronic ulcerative colitis: a clinical, pathological, and molecular review. Am J Gastroenterol 1999;94: Friedman S, Odze RD, Farraye FA. Management of neoplastic polyps in inflammatory bowel disease. Inflamm Bowel Dis 2003; 9: Rubin PH, Friedman S, Harpaz N, Goldstein E, Weiser J, Schiller J, Waye JD, Present DH. Colonoscopic polypectomy in chronic colitis: conservative management after endoscopic resection of dysplastic polyps. Gastroenterology 1999;117: Engelsgjerd M, Farraye FA, Odze RD. Polypectomy may be adequate treatment for adenoma-like dysplastic lesions in chronic ulcerative colitis. Gastroenterology 1999;117: Ullman T, Croog V, Harpaz N, Sachar D, Itzkowitz S. Progression of flat low-grade dysplasia to advanced neoplasia in patients with ulcerative colitis. Gastroenterology 2003;125: Ullman TA, Loftus EV, Kakar S, Burgart LJ, Sandborn WJ, Tremaine WJ. The fate of low grade dysplasia in ulcerative colitis. Am J Gastroenterol 2002;97: Gorfine SR, Bauer J, Harris MT, Kreel I. Dysplasia complicating chronic ulcerative colitis: is immediate colectomy warranted? Dis Colon Rectum 2000;43: Tytgat GNJ, Dhir V, Gopinath N. Endoscopic appearance of dysplasia and cancer in inflammatory bowel disease. Eur J Cancer 1995;31A: Blackstone MO, Riddell RH, Rogers BHG, Levin B. Dysplasiaassociated lesion or mass (DALM) detected by colonoscopy in long-standing ulcerative colitis: an indication for colectomy. Gastroenterology 1981;80: Butt JH, Konishi F, Morson BC, Lennard-Jones JE, Ritchie JK. Macroscopic lesions in dysplasia and carcinoma complicating ulcerative colitis. Dig Dis Sci 1983;28: Bond JH. Polyp guideline: diagnosis, treatment, and surveillance for patients with colorectal polyps. Practice parameters committee of the American College of Gastroenterology. Am J Gastroenterol 2000;95: Walsh SV, Loda M, Torres CM, Antonioli D, Odze RD. p53 and catenin expression in chronic ulcerative colitis-associated polypoid dysplasia and sporadic adenomas: an immunohistochemical study. Am J Surg Pathol 1999;23: Odze R, Brown CA, Noffsinger AE, Fogt F. Genetic alterations in chronic ulcerative colitis associated adenoma-like DALMs are

8 July 2004 ADENOMAS IN UC 541 similar to non-colitic sporadic adenomas. Am J Surg Pathol 2000; 24: Selaru FM, Xu Y, Yin J, Zou T, Liu TC, Mori Y, Abraham JM, Sato F, Wang S, Twigg C, Olaru A, Shustova V, Leytin A, Hytiroglou P, Shibata D, Harpaz N, Meltzer SJ. Artificial neural networks distinguish among subtypes of neoplastic colorectal lesion. Gastroenterology 2000;122: Fogt F, Vortmeyer AO, Goldman H, Giordano TJ, Merino MJ, Zhuang Z. Comparison of genetic alterations in colonic adenoma and ulcerative colitis-associated dysplasia and carcinoma. Hum Pathol 1998;29: Medlicott SAC, Jewell LD, Price L, Fedorak RN, Sherbaniuk RW, Urbanski SJ. Conservative management of small adenomata in ulcerative colitis. Am J Gastroenterol 1997;92: Nugent FW, Haggitt RC, Gilpin PA. Cancer surveillance in ulcerative colitis. Gastroenterology 1991;100: Marchesa P, Lashner BA, Lavery IC, Milsom J, Hull TL, Strong SA, Church JM, Navarro G, Fazio VW. The risk of cancer and dysplasia among ulcerative colitis patients with primary sclerosing cholangitis. Am J Gastroenterol 1997;92: Shetty K, Rybicki L, Brezinski A, Carey WD, Lashner BA. The risk of cancer or dysplasia in ulcerative colitis patients with primary sclerosing cholangitis. Am J Gastroenterol 1999;94: Lennard-Jones JE, Melville DM, Morson BC, Ritchie JK, Williams CB. Precancer and cancer in extensive ulcerative colitis: findings among 401 patients over 22. Gut 1990;31: Ekbom A, Helmick C, Zack M, Adami H. Ulcerative colitis and colorectal cancer: a population-based study. N Engl J Med 1990; 323: Address requests for reprints to: Robert D. Odze, M.D., F.R.C.P.C., Associate Professor, Chief, GI Pathology Service, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts rodze@partners.org; fax: (617)