Ulcerative colitis with low-grade dysplasia

Abstract

Clinical caseA 37-year-old woman with a 17-year history of ulcerative colitis that extends up to the mid-descending colon undergoes routine surveillance colonoscopy. Her disease is quiescent at the time of the procedure (and has been for 5 years) and no lesions or masses are identified. Thirty-six biopsies are taken from 10-cm intervals up to the cecum. Histological exam reveals findings consistent with idiopathic inflammatory bowel disease in the rectum, sigmoid colon, and descending colon. Three biopsies from her sigmoid colon are reported as low-grade dysplasia. The biopsies are sent to a local university pathologist with a special interest in GI pathology, and she suggests that the biopsies are indeterminate for dysplasia. The patient returns for a repeat dysplasia surveillance endoscopy 3 months later and 8 extra biopsies are obtained from the sigmoid and descending colon. Four biopsies from her sigmoid colon are identified as containing low-grade dysplasia, and there is agreement between the 2 pathologists.BackgroundThe incidence of colon cancer is increased in ulcerative colitis (UC). It is estimated to occur in 1 of 333 to 1 of 400 patient-years1Bernstein C.N. Kliewer E. Wajda A. Blanchard J.F. The incidence of cancer among patients with IBD a population-based study.Cancer. 2001; 91: 854-862Crossref PubMed Scopus (1003) Google Scholar, 2Eaden J.A. Abrams K.R. Mayberry J.F. The risk of CRC in ulcerative colitis a meta-analysis.Gut. 2001; 48: 526-535Crossref PubMed Scopus (2246) Google Scholar and up to 18% of patients with a colon intact by 30 years of disease may develop colon cancer.2Eaden J.A. Abrams K.R. Mayberry J.F. The risk of CRC in ulcerative colitis a meta-analysis.Gut. 2001; 48: 526-535Crossref PubMed Scopus (2246) Google Scholar These data reflect increased risks compared to the general population of 2.6–5.4-fold.1Bernstein C.N. Kliewer E. Wajda A. Blanchard J.F. The incidence of cancer among patients with IBD a population-based study.Cancer. 2001; 91: 854-862Crossref PubMed Scopus (1003) Google Scholar, 3Ekbom A. Helmick C. Zack M. Adami H. Ulcerative colitis and CRC. A population-based study.N Engl J Med. 1990; 323: 1228-1233Crossref PubMed Scopus (1542) Google Scholar A strategy to screen for colon cancer in UC has involved interval colonoscopy with random biopsying at multiple sites throughout the colon and from worrisome-appearing mass lesions. The biopsies are assessed for dysplasia (an unequivocal neoplastic change confined to the epithelium), or for invasive cancer. To simplify and unify the diagnosis of dysplasia, a scheme of dysplasia diagnoses that includes negative, low-grade, high-grade, and indeterminate was devised.4Riddell R.H. Goldman H. Ransohoff D.F. Appelman H.D. Fenoglio C.M. Haggitt R.C. Ahren C. Correa P. Hamilton S.R. Morson B.C. et al.Dysplasia in inflammatory bowel disease standardized classification with provisional clinical applications.Hum Pathol. 1983; 14: 931-968Abstract Full Text PDF PubMed Scopus (1589) Google Scholar There has been no uniform approach to dysplasia surveillance in terms of number of biopsies or number of sites in published studies,5Bernstein C.N. Shanahan F. Weinstein W.M. Are we telling patients the truth about surveillance colonoscopy in ulcerative colitis?.Lancet. 1994; 343: 71-74Abstract PubMed Scopus (511) Google Scholar and this has led to a lack of uniform approach in clinical practice.6Bernstein C.N. Weinstein W.M. Levine D.S. Shanahan F. Physicians’ perceptions of dysplasia and approaches to surveillance colonoscopy in ulcerative colitis.Am J Gastroenterol. 1995; 90: 2006-2114PubMed Google Scholar, 7Eaden J.A. Ward B.A. Mayberry J.F. How gastroenterologists screen for colonic cancer in ulcerative colitis an analysis of performance.Gastrointest Endosc. 2000; 51: 123-128Abstract Full Text Full Text PDF PubMed Scopus (187) Google Scholar A number of studies help to formulate a rational strategy of endoscopy frequency and biopsy number and sites.The risk for dysplasia increases after 8 years of disease. All UC studies that involve disease duration are complicated by the difficulty in deciding when the disease in any one patient begins. Is it at date of diagnosis or date of symptom onset? At first colonoscopy for surveillance, approximately 10% of subjects will have dysplasia or cancer already present.5Bernstein C.N. Shanahan F. Weinstein W.M. Are we telling patients the truth about surveillance colonoscopy in ulcerative colitis?.Lancet. 1994; 343: 71-74Abstract PubMed Scopus (511) Google Scholar, 8Connell W.R. Lennard-Jones J.E. Williams C.B. Talbot I.C. Price A.B. Wilkinson K.H. Factors affecting the outcome of endoscopic surveillance for cancer in ulcerative colitis.Gastroenterology. 1994; 107: 934-944PubMed Google Scholar Hence, while most dysplasia surveillance programs begin at 8 years from disease diagnosis it is prudent to pursue a surveillance endoscopy with multiple biopsies if a patient is being endoscoped for clinical staging of extent or severity prior to 8 years. I would pursue a full dysplasia surveillance endoscopy before 8 years from diagnosis particularly if there are additional risk factors such as a concurrent diagnosis of primary sclerosing cholangitis. If a surveillance endoscopy prior to 8 years is negative for dysplasia, I would only begin an ongoing dysplasia surveillance program after 8 years (Table 1).Table 1An Endoscopy and Biopsy Approach to Dysplasia Surveillance in Ulcerative Colitis 1.Begin at 8 years of disease.2.Take 4 biopsies from at least 9 sites throughout the colon, ensuring at least 4 sites from the rectum and sigmoid.3.If there is no endoscopic inflammation from mid or right colon, 2 biopsies may be sufficient in loci from these sites, unless it is known there is microscopic evidence of disease.4.If the biopsies are negative for dysplasia at the first surveillance, then repeat the endoscopic surveillance at 1 year, and then if negative, pursue repeat endoscopies every 3 years until 20 years of disease.5.At 20 years pursue dysplasia surveillance annually.6.If biopsies are indeterminate for dysplasia then maximize anti-inflammatory therapy and repeat the endoscopic surveillance in 3–6 months.7.Special circumstances: If patients have PSC or first-degree relatives with sporadic colon cancer, consider endoscopic surveillance prior to 8 years of disease duration and consider a reduced interval between 9 and 20 years of disease duration (i.e., every 1 to 2 years rather than every 3 years). Open table in a new tab If the initial endoscopy in a surveillance program is negative for dysplasia, the incidence of developing dysplasia over time has been estimated at approximately 3%.5Bernstein C.N. Shanahan F. Weinstein W.M. Are we telling patients the truth about surveillance colonoscopy in ulcerative colitis?.Lancet. 1994; 343: 71-74Abstract PubMed Scopus (511) Google Scholar, 8Connell W.R. Lennard-Jones J.E. Williams C.B. Talbot I.C. Price A.B. Wilkinson K.H. Factors affecting the outcome of endoscopic surveillance for cancer in ulcerative colitis.Gastroenterology. 1994; 107: 934-944PubMed Google Scholar Therefore, after 2 consecutive negative annual dysplasia surveillance endoscopies I would extend the surveillance interval to every 3 years. At 20 years of disease the risk rises at a steeper rate and it is prudent to conduct surveillance endoscopies annually.It is estimated that 18 biopsies are required to have a sensitivity of 95% at picking up neoplasia when present (that is picking up any grade of dysplasia if cancer is present).9Rubin C.E. Haggitt R.C. Burmer G.C. Brentnall T.A. Stevens A.C. Levine D.S. Dean P.J. Kimmey M. Perera D.R. Rabinovitch P.S. DNA aneuploidy in colonic biopsies predicts future development of dysplasia in ulcerative colitis.Gastroenterology. 1992; 103: 1611-1620Abstract PubMed Google Scholar Thirty-three biopsies and 64 biopsies are required to have a sensitivity of 90% and 95%, respectively, of picking up the highest grade of neoplasia.9Rubin C.E. Haggitt R.C. Burmer G.C. Brentnall T.A. Stevens A.C. Levine D.S. Dean P.J. Kimmey M. Perera D.R. Rabinovitch P.S. DNA aneuploidy in colonic biopsies predicts future development of dysplasia in ulcerative colitis.Gastroenterology. 1992; 103: 1611-1620Abstract PubMed Google Scholar Hence, 30–40 biopsies may be recommended to enhance the likelihood of finding dysplasia. Furthermore, it is appropriate to increase sampling from the rectosigmoid (this can be achieved by adding at least 2 additional sampling sites from the rectum and sigmoid) since that area is the most common site for cancer presentation.10Connell W.R. Talbot I.C. Harpaz N. Britto N. Wilkinson K.H. Kamm M.A. Lennard-Jones J.E. Clinicopathological characteristics of carcinoma complicating ulcerative colitis.Gut. 1994; 35: 1419-1423Crossref PubMed Scopus (174) Google Scholar, 11Choi P.M. Nugent F.W. Schoetz D.J. Silverman M.L. Haggitt R.C. Colonoscopic surveillance reduces mortality from colorectal cancer in ulcerative colitis.Gastroenterology. 1993; 105: 418-424Abstract PubMed Google Scholar, 12Shelton A.A. Lehman R.E. Schrock T.R. Welton M.L. Retrospective review of colorectal cancer in ulcerative colitis at a tertiary center.Arch Surg. 1996; 131: 806-810Crossref PubMed Scopus (36) Google Scholar, 13Schneider A. Stolte M. Clinical and pathomorphological findings in patients with colorectal carcinoma complicating ulcerative colitis.Z Gastroenterol. 1993; 31: 192-197PubMed Google Scholar, 14von Herbay A. Herfarth C. Otto H.F. Cancer and dysplasia in ulcerative colitis a histologic study of 301 surgical specimen.Z Gastroenterol. 1994; 32: 382-388PubMed Google ScholarRecently it has been reported that neoplasia in UC significantly correlated with both histologic and endoscopic inflammation.15Rutter M. Saunders B. Wilkinson K. Rumbles S. Schofield G. Kamm M. Williams C. Price A. Talbot I. Forbes A. Severity of inflammation is a risk factor for colorectal neoplasia in ulcerative colitis.Gastroenterology. 2004; 126: 451-459Abstract Full Text Full Text PDF PubMed Scopus (981) Google Scholar The fact that inflammation is commonly most pronounced in the left colon would support enhanced sampling from the left colon. In patients with endoscopic left-sided colitis and normal appearing transverse or right colonic mucosa it is appropriate to sample these endoscopically normal appearing areas but perhaps with 2 biopsies per site rather than 4. The rationale is to determine if there is microscopic evidence of disease that would warrant enhanced sampling the next time dysplasia surveillance is pursued. Another recent paper reported that it was critical to biopsy noninflamed mucosa in UC because it was often histologically inflamed and at times was the site of neoplasia.16Mathy C. Schneider K. Chen Y.Y. Varma M. Terdiman J.P. Mahadevan U. Gross versus microscopic pancolitis and the occurrence of neoplasia in ulcerative colitis.Inflamm Bowel Dis. 2003; 9: 351-355Crossref PubMed Scopus (85) Google ScholarA finding of “indeterminate for dysplasia” warrants more surveillance. If it arises in the setting of active inflammation the best strategy would be for maximizing anti-inflammatory therapy before repeating the surveillance endoscopy. Performing the endoscopy within 3 months seems optimal as there is no advantage to waiting, particularly if the indeterminate is really a true dysplasia waiting to be clarified.Special circumstances (enhanced risk)There are 3 studies that have identified that having a first-degree relative with colon cancer but unaffected by inflammatory bowel disease increases the risk to the UC patient.17Nuako K.W. Ahlquist D.A. Mahoney D.W. Schaid D.J. Siems D.M. Lindor N.M. Familial predisposition for colorectal cancer in chronic ulcerative colitis a case control study.Gastroenterology. 1998; 115: 1079-1083Abstract Full Text Full Text PDF PubMed Scopus (195) Google Scholar, 18Eaden J. Abrams K. Ekbom A. Jackson E. Mayberry J. Colorectal cancer prevention in ulcerative colitis a case-control study.Aliment Pharmacol Ther. 2000; 14: 145-153Crossref PubMed Scopus (513) Google Scholar, 19Askling J. Dickman P.W. Karlen P. Brostrom O. Lapidus A. Lofberg R. Ekbom A. Family history as a risk factor for colorectal cancer in inflammatory bowel disease.Gastroenterology. 2001; 120: 1356-1362Abstract Full Text Full Text PDF PubMed Scopus (355) Google Scholar These data underscore the need to query UC patients as to their family histories of colon cancer. There are a series of studies showing an increased risk for dysplasia among patients with primary sclerosing cholangitis (PSC).20Broome U. Lofberg R. Veress B. Eriksson L.S. Primary sclerosing cholangitis and ulcerative colitis evidence for increased neoplastic potential.Hepatology. 1995; 22: 1404-1408PubMed Google Scholar, 21D’Haens G.R. Lashner B.A. Hanauer S.B. Pericholangitis and sclerosing cholangitis are risk factors for dysplasia and cancer in ulcerative colitis.Am J Gastroenterol. 1993; 88: 1174-1178PubMed Google Scholar, 22Brentnall T.A. Haggitt R.C. Rabinovitch P.S. Kimmey M.B. Bronner M.P. Levine D.S. Kowdley K.V. Stevens A.C. Crispin D.A. Emond M. Rubin C.E. Risk and natural history of colonic neoplasia in patients with primary sclerosing cholangitis and ulcerative colitis.Gastroenterology. 1996; 110: 331-338Abstract Full Text PDF PubMed Scopus (283) Google Scholar, 23Kornfeld D. Ekbom A. Ihre T. Is there an excess risk for colorectal cancer in patients with ulcerative colitis and concomitant primary sclerosing cholangitis? A population based study.Gut. 1997; 41: 522-525Crossref PubMed Scopus (233) Google Scholar, 24Shetty K. Rybicki L. Brzezinski A. Carey W.D. Lashner B.A. The risk for cancer or dysplasia in ulcerative colitis patients with primary sclerosing cholangitis.Am J Gastroenterol. 1999; 94: 1643-1649Crossref PubMed Scopus (243) Google Scholar It would be reasonable in these instances to increase the surveillance interval between 8 and 20 years of disease to every 1 to 2 years rather than every 3 years. Since patients with PSC who undergo liver transplantation become immunocompromised it would be prudent to pursue dysplasia surveillance in these patients annually.While the risk is increased among those with pancolitis compared with those with left-sided colitis it is simpler to pursue a similar strategy regardless of disease extent. If a distinct strategy was to be adopted for initiating dysplasia surveillance later in the disease course for patients with left-sided colitis, then the clinician would have to be mindful of discerning whether or not patients with left-sided colitis have progressed to disease beyond the splenic flexure.The one exception appears to be patients with ulcerative proctitis. This diagnosis applies to patients with inflammation limited to the rectum and proven to have no acute or chronic inflammatory changes more proximally. These patients have not been proven to have an increased risk of rectal cancer. If dysplasia surveillance is not undertaken in these cases it is imperative that biopsies have been taken at 18 cm from the anal verge and beyond to ensure that the patient has true proctitis and not simply endoscopic proctitis but histologic evidence of sigmoiditis.Does dysplasia surveillance save lives?There have been no randomized controlled trials proving the value of dysplasia surveillance versus no surveillance.25Bernstein C.N. Challenges in designing a randomized trial of surveillance colonoscopy in IBD.Inflamm Bowel Dis. 1998; 4: 132-141PubMed Google Scholar There has been circumstantial evidence that it can be better than no surveillance. Two studies have reported that patients undergoing surveillance endoscopies who present with cancer have earlier-stage cancer than those not undergoing surveillance who present with cancer.11Choi P.M. Nugent F.W. Schoetz D.J. Silverman M.L. Haggitt R.C. Colonoscopic surveillance reduces mortality from colorectal cancer in ulcerative colitis.Gastroenterology. 1993; 105: 418-424Abstract PubMed Google Scholar, 26Karlen P. Kornfeld D. Brostrom O. Lofberg R. Persson P.G. Ekbom A. Is colonoscopic surveillance reducing colorectal cancer mortality in ulcerative colitis? A population based case control study.Gut. 1998; 42: 711-714Crossref PubMed Scopus (251) Google Scholar However, an improvement in survival due to identification of earlier stage cancer with surveillance has not been proven.Potential management strategiesPursue further routine surveillance until high-grade dysplasia (or a more advanced lesion) is foundA controversy that is still debated is the clinician’s response to low-grade versus high-grade dysplasia. While most clinicians pursue colectomy for high-grade dysplasia,6Bernstein C.N. Weinstein W.M. Levine D.S. Shanahan F. Physicians’ perceptions of dysplasia and approaches to surveillance colonoscopy in ulcerative colitis.Am J Gastroenterol. 1995; 90: 2006-2114PubMed Google Scholar, 7Eaden J.A. Ward B.A. Mayberry J.F. How gastroenterologists screen for colonic cancer in ulcerative colitis an analysis of performance.Gastrointest Endosc. 2000; 51: 123-128Abstract Full Text Full Text PDF PubMed Scopus (187) Google Scholar some still believe in enhanced surveillance for low-grade dysplasia.29Lim C.H. Dixon M.F. Vail A. Forman D. Lynch D.A.F. Axon A.T.R. Ten year follow up of ulcerative colitis patients with and without low grade dysplasia.Gut. 2003; 52: 1127-1132Crossref PubMed Scopus (204) Google Scholar The initial development of the scheme to differentiate low-grade dysplasia from high-grade dysplasia, although intended to simplify pathology reporting, has potentially created a false sense of security for clinicians when low-grade dysplasia is diagnosed (Table 2). There is a perceived sense that an evolution from low-grade to high-grade dysplasia is a continuum. Unfortunately, when low-grade dysplasia is the preoperative diagnosis nearly 1 in 5 patients may already have a cancer present.5Bernstein C.N. Shanahan F. Weinstein W.M. Are we telling patients the truth about surveillance colonoscopy in ulcerative colitis?.Lancet. 1994; 343: 71-74Abstract PubMed Scopus (511) Google Scholar Figure 1 is an example of dysplasia in the superficial mucosa (the part that would be accessed at endoscopic biopsy) with frank cancer extending from the lamina propria to the submucosa. It is possible that endoscopic biopsies would have picked up the dysplasia and missed the cancer at this site. Furthermore, low-grade dysplasia is the only dysplasia found near or at a distance from frank colon cancers in UC in approximately 50% of cases (and not high-grade dysplasia as might be expected if there was a definite continuum).10Connell W.R. Talbot I.C. Harpaz N. Britto N. Wilkinson K.H. Kamm M.A. Lennard-Jones J.E. Clinicopathological characteristics of carcinoma complicating ulcerative colitis.Gut. 1994; 35: 1419-1423Crossref PubMed Scopus (174) Google Scholar In approximately 25% of cancers at resection, when deeper sections are cut, dysplasia cannot even be found.8Connell W.R. Lennard-Jones J.E. Williams C.B. Talbot I.C. Price A.B. Wilkinson K.H. Factors affecting the outcome of endoscopic surveillance for cancer in ulcerative colitis.Gastroenterology. 1994; 107: 934-944PubMed Google Scholar, 30Ransohoff D.F. Riddell R.H. Levin B. Ulcerative colitis and colonic cancer problems in assessing the diagnostic usefulness of mucosal dysplasia.Dis Colon Rectum. 1985; 28: 383-388Crossref PubMed Scopus (133) Google Scholar, 31Taylor B.A. Pemberton J.H. Carpenter H.A. Levin K.E. Schroeder K.W. Welling D.R. Spencer M.P. Zinsmeister A.R. Dysplasia in chronic ulcerative colitis implications for colonoscopic surveillance.Dis Colon Rectum. 1992; 35: 950-956Crossref PubMed Scopus (131) Google Scholar Low-grade dysplasia has been shown to progress to high-grade dysplasia or cancer in approximately 35%–50% by 5 years.8Connell W.R. Lennard-Jones J.E. Williams C.B. Talbot I.C. Price A.B. Wilkinson K.H. Factors affecting the outcome of endoscopic surveillance for cancer in ulcerative colitis.Gastroenterology. 1994; 107: 934-944PubMed Google Scholar, 32Lindberg B. Persson B. Veress B. Ingelman-Sundberg H. Granqvist S. Twenty years’ colonoscopic surveillance of patients with ulcerative colitis. Detection of dysplastic and malignant transformation.Scand J Gastroenterol. 1996; 31: 1195-1204Crossref PubMed Scopus (88) Google Scholar, 33Ullman 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: 1311-1319Abstract Full Text Full Text PDF PubMed Scopus (329) Google Scholar Hence, waiting on low-grade dysplasia makes little sense for the patient’s best interests (unless the patient is a poor operative candidate). Also, the finding of unifocal versus multifocal dysplasia seems to carry the same high risk.33Ullman 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: 1311-1319Abstract Full Text Full Text PDF PubMed Scopus (329) Google ScholarTable 2The Arguments in Favor of Pursuing Colectomy for Low-grade Dysplasia and for the Absence of Support for a Uniform Evolution of Low-grade Dysplasia Through a Continuum to High-grade Dysplasia and Cancer 1.When low-grade dysplasia is the diagnosis at surveillance colonoscopy nearly 1 in 5 patients may already have cancer present.5Bernstein C.N. Shanahan F. Weinstein W.M. Are we telling patients the truth about surveillance colonoscopy in ulcerative colitis?.Lancet. 1994; 343: 71-74Abstract PubMed Scopus (511) Google Scholar2.Low-grade dysplasia is the only dysplasia found near or at a distance from frank colorectal cancer in approximately 50% of cases.10Connell W.R. Talbot I.C. Harpaz N. Britto N. Wilkinson K.H. Kamm M.A. Lennard-Jones J.E. Clinicopathological characteristics of carcinoma complicating ulcerative colitis.Gut. 1994; 35: 1419-1423Crossref PubMed Scopus (174) Google Scholar3.In approximately 25% of cancers at resection when deeper sections are cut, dysplasia cannot be found.8Connell W.R. Lennard-Jones J.E. Williams C.B. Talbot I.C. Price A.B. Wilkinson K.H. Factors affecting the outcome of endoscopic surveillance for cancer in ulcerative colitis.Gastroenterology. 1994; 107: 934-944PubMed Google Scholar, 30Ransohoff D.F. Riddell R.H. Levin B. Ulcerative colitis and colonic cancer problems in assessing the diagnostic usefulness of mucosal dysplasia.Dis Colon Rectum. 1985; 28: 383-388Crossref PubMed Scopus (133) Google Scholar, 31Taylor B.A. Pemberton J.H. Carpenter H.A. Levin K.E. Schroeder K.W. Welling D.R. Spencer M.P. Zinsmeister A.R. Dysplasia in chronic ulcerative colitis implications for colonoscopic surveillance.Dis Colon Rectum. 1992; 35: 950-956Crossref PubMed Scopus (131) Google Scholar4.Low-grade dysplasia progresses to high-grade dysplasia or cancer in up to 50% of cases within 5 years.8Connell W.R. Lennard-Jones J.E. Williams C.B. Talbot I.C. Price A.B. Wilkinson K.H. Factors affecting the outcome of endoscopic surveillance for cancer in ulcerative colitis.Gastroenterology. 1994; 107: 934-944PubMed Google Scholar, 32Lindberg B. Persson B. Veress B. Ingelman-Sundberg H. Granqvist S. Twenty years’ colonoscopic surveillance of patients with ulcerative colitis. Detection of dysplastic and malignant transformation.Scand J Gastroenterol. 1996; 31: 1195-1204Crossref PubMed Scopus (88) Google Scholar, 33Ullman 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: 1311-1319Abstract Full Text Full Text PDF PubMed Scopus (329) Google Scholar Open table in a new tab If the patient was adamant about not undergoing surgery then further surveillance as opposed to doing nothing would be in order. If the patient develops a more advanced lesion (including cancer) with further surveillance, she may be less reluctant to consider surgery.Pursue further surveillance with chromoendoscopyRecently it has been shown that chromoendoscopy can enhance dysplasia surveillance. In a randomized study comparing routine dysplasia surveillance to surveillance with chromoendoscopy, the chromoendoscopy arm turned up significantly more dysplastic lesions.34Kiesslich R. Fritsch J. Holtmann M. Koehler H.H. Stolte M. Kanzler S. Nafe B. Jung M. Galle P.R. Neurath M.F. Methylene blue aided chromoendoscopy for the detection of intraepithelial neoplasia and colon cancer in ulcerative colitis.Gastroenterology. 2003; 124: 880-888Abstract Full Text Full Text PDF PubMed Scopus (778) Google Scholar In another European study chromoendoscopy that immediately followed a routine surveillance endoscopy led to more dysplastic lesions being identified.35Rutter M.D. Saunders B.P. Schofield G. Forbes A. Price A.B. Talbot I.C. Pancolonic indigo carmine dye spraying for the detection of dysplasia in ulcerative colitis.Gut. 2004; 53: 256-260Crossref PubMed Scopus (504) Google Scholar Issues to be resolved with chromoendoscopy include whether a magnifying endoscope is truly required, what type of dye is optimal (indigo carmine versus methylene blue), and whether a surface mucolytic or an antispasmodic agent is required. Nevertheless, chromoendoscopy is something that can be added without much extra cost now in most endoscopy suites (simply using a spray catheter and one of the dyes). However, the patient already has documented low-grade dysplasia, and multifocality has not been shown to pose a greater risk that cancer is present than unifocality.33Ullman 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: 1311-1319Abstract Full Text Full Text PDF PubMed Scopus (329) Google ScholarPursue anti-inflammatory therapy with 5-ASA to reverse dysplasiaRecently there has been heightened interest in the notion that 5-aminosalicylates (5-ASA) might be preventative against colon cancer development in UC.36Bernstein C.N. Eaden J. Steinhart A.H. Munkholm P. Gordon P.H. Cancer prevention in inflammatory bowel disease and the chemoprophylactic potential of 5-aminosalicylic acid.Inflamm Bowel Dis. 2002; 8: 356-361Crossref PubMed Scopus (69) Google Scholar A group of Danish investigators believe that their low risk of colorectal cancer in UC is secondary to high rates of chronic 5-ASA use.38Langholz E. Munkholm P. Davidsen M. Binder V. Colorectal cancer risk and mortality in patients with ulcerative colitis.Gastroenterology. 1992; 103: 1444-1451Abstract PubMed Google Scholar A case-control study from the United Kingdom reported markedly reduced rates of colon cancer among users of at least 1.2 g/day of 5-ASA.18Eaden J. Abrams K. Ekbom A. Jackson E. Mayberry J. Colorectal cancer prevention in ulcerative colitis a case-control study.Aliment Pharmacol Ther. 2000; 14: 145-153Crossref PubMed Scopus (513) Google Scholar However, this same study showed that having at least 2 physician visits, having at least 2 colonoscopies, and using prednisone also reduced the risk. Hence, active follow-up with medical care and treatment may reduce the risk, and this risk reduction may not be specific to 5-ASA use. In a population-based, case-control study from Manitoba 5-ASA use for 2 years was not associated with a reduced risk of colorectal cancer in IBD patients.39Bernstein C.N. Metge C. Blanchard J.F. Yogendran M. Does the use of 5-aminosalicylates in inflammatory bowel disease prevent the development of colorectal cancer?.Am J Gastroenterol. 2003; 98: 2784-2788Crossref PubMed Scopus (110) Google Scholar It will be important to repeat this study when there are more years of 5-ASA use that can be assessed. In the study showing the correlation between inflammation and neoplasia the case-control design could not show a statistically significant benefit of long-term 5-ASA use reducing neoplasia risk.16Mathy C. Schneider K. Chen Y.Y. Varma M. Terdiman J.P. Mahadevan U. Gross versus microscopic pancolitis and the occurrence of neoplasia in ulcerative colitis.Inflamm Bowel Dis. 2003; 9: 351-355Crossref PubMed Scopus (85) Google Scholar Although having inflammation may correlate with neoplasia risk, the corollary that reducing inflammation with a 5-ASA agent for instance, can reverse neoplasia, while tantalizing, is yet to be proved.Once definite dysplasia has developed there is certainly no indication for recommending 5-ASA to prevent dysplasia progression, and a preliminary report from New York has examined this recommendation.40Ullman T. Croog V. Harpaz N. Itzkowitz S. Kornbluth A. Preventing neoplastic progression in ulcerative colitis role of mesalamine.Gastroenterology. 2003; 124: A242Abstract Full Text PDF Google Scholar A chemotherapeutic agent for definite dysplasia does not exist at present.Thermal ablation of the dysplastic areaLow-grade dysplasia in Barrett’s esophagus is typically approached with further surveillance and if high-grade dysplasia or even localized cancers evolve, some consider thermal ablation an alternative to esophagectomy.41Overholt B.F. Panjehpour M. Halberg D.L. Photodynamic therapy for Barrett’s esophagus with dysplasia and/or early stage carcinoma long-term results.Gastrointest Endosc. 2003; 58: 183-188Abstract Full Text PDF PubMed Scopus (282) Google Scholar These procedures are considered experimental since long-term outcome data are still evolving. This approach has never been considered in ulcerative colitis, likely because of the vast terrain that would have to be covered compared with the area covered by the Barrett’s mucosa. The safety of thermal ablation to a much larger surface such as the colon mucosa (compared wit