J Gastrointest Surg (2014) 18:1229–1230 DOI 10.1007/s11605-014-2499-z
SSAT/ASCRS JOINT SYMPOSIUM
Endoscopic Evaluation of Dysplasia in Ulcerative Colitis Jeffrey M. Marks
Received: 7 October 2013 / Accepted: 10 March 2014 / Published online: 25 March 2014 # 2014 The Society for Surgery of the Alimentary Tract
Keywords Ulcerative colitis . Endoscopic surveillance . Optical biopsy . Cancer
Ulcerative colitis is a disease which predisposes patients to development of colorectal cancer (CRC). Standard of care in 2012 is surveillance colonoscopy at intervals based on duration of disease and patient age. Presently, multiple biopsies are taken to identify precursors for cancer such as dysplastic cells. Although the actual development of CRC is low, more efficient and effective techniques for identification and surveillance for dysplasia would benefit this population of patients. This brief summary will overview some of the newer endoscopic adjuncts being used in surveillance of ulcerative colitis (UC) and their application. First, there are several assumptions that must be accepted when it comes to the use of surveillance for dysplasia in patients with UC. First, that dysplasia develops initially as a single cell and follows a progression from non-dysplasia to low-grade dysplasia (LGD) to high-grade dysplasia (HGD) to actual CRC. Second, that larger dysplastic fields have been growing for longer and have a higher risk of HGD or CRC, and that taking more random biopsies increases the odds of finding smaller fields of dysplastic cells. The present standard for surveillance includes the technique of four-quadrant biopsies every 10 cm (approx 32 biopsies). This results in approximately 1/2500th of colonic surface area being removed for histologic evaluation. The final assumption is that the finding of HGD on random biopsy is associated with a 40 % risk of
J. M. Marks (*) Department of Surgery, University Hospitals Case Medical Center, 11100 Euclid Ave, Mail Stop LKS 5047, Cleveland, OH 44106, USA e-mail: [email protected]
synchronous CRC and the finding of LGD is associated with a 20 % risk of synchronous CRC. Despite the unclear answers regarding these assumptions and the actual progression of dysplasia to CRC, it has been shown that UC patients undergoing surveillance will have a much lesser risk of dying from CRC than do non-surveyed patients. These standard practices of surveillance endoscopy with routine colonoscopic techniques are being challenged now by the development of enhanced endoscopy which includes c h r o m o e n d o s o c o p y, n a r r o w b a n d i m a g i n g , a n d autoflorescence, all of which have been described to identify foci of dysplasia as small as 2 mm. Probe-based confocal laser endomicroscopy, in pilot studies has been shown to identify aberrant crypt foci (ACF), which may be the earliest recognizable step of transformation in colonic multiphase carcinogenesis.1 In one series, a stepwise increase in the number of ACF from patients with non-dysplasia to dysplasia and then to cancer was identified.2 Univariate and multivariate analyses showed significant correlations between ACF and dysplasia, and the authors proposed an ACF-dysplasiacancer sequence in colitis-associated carcinogenesis similar to the ACF-adenoma-carcinoma sequence in sporadic CRC. Another technique of enhanced endoscopy, autofluorescence (AF) imaging colonoscopy, has also been studied for the detection of dysplastic lesions. However, the rate of positive dysplasia was not statistically different between lesions determined to be low AF (14 %) and those to be high AF (5 %).3 One final mode of enhanced endoscopy, narrow band imaging (NBI), has also been evaluated in a similar manner for detection of dysplasia with lesion patterns being specifically described. In one study that used both conventional endoscopy and NBI, a significant percentage of lesions were
1230
recognized by conventional methods but not NBI, thereby suggesting that both methods would have to be used for the procedure to provide adequate detection of dysplastic lesions.4 In another study evaluating NBI, the positive rate of dysplasia was higher in protruding lesions (2/20 sites, 10 %) than in flat mucosa (3/276 sites, 1.1 %).5 In addition, when the surface pattern was taken into account, the rate of positive dysplasia was higher in a tortuous mucosal pattern (4/50 sites, 8 %) than in the honeycomb-like or villous patterns identified (1/246 sites, 0.4 %). They concluded that the tortuous pattern determined by NBI colonoscopy may be a clue for the identification of dysplasia during surveillance for UC. In conclusion, to date, there is still not a close relation between the conventional endoscopic image and histological assessment of dysplasia in patients with UC undergoing surveillance colonoscopy. Clinical implications of the findings from enhanced endoscopy are not yet available, although they most likely will be in the near future. Therefore, in 2012, standard random biopsies as described above remain the gold standard for surveillance in patients with ulcerative colitis.
J Gastrointest Surg (2014) 18:1229–1230
References 1. Gastroenterol Res Pract. 2012;2012:645173. Epub 2012 Apr 8.Probebased confocal laser endomicroscopy evaluation of colon preneoplastic lesions, with particular attention to the aberrant crypt foci, and comparative assessment with histological features obtained by conventional endoscopy. Mascolo M, Staibano S, Ilardi G, Siano M, Vecchione ML, Esposito D, De Rosa G, De Palma GD. 2. Clin Cancer Res. 2008 Jan 1;14(1):48–54. Aberrant crypt foci as precursors of the dysplasia-carcinoma sequence in patients with ulcerative colitis. Kukitsu T, Takayama T, Miyanishi K, Nobuoka A, Katsuki S, Sato Y, Takimoto R, Matsunaga T, Kato J, Sonoda T, Sakamaki S, Niitsu Y. 3. Colorectal Dis. 2010 Oct;12(10 Online):e291-7. doi: 10.1111/j.14631318.2009.02181.x. Autofluorescence imaging colonoscopy for the detection of dysplastic lesions in ulcerative colitis: a pilot study. Matsumoto T, Nakamura S, Moriyama T, Hirahashi M, Iida M 4. Am J Gastroenterol. 2012 Apr;107(4):543–50. doi: 10.1038/ajg.2012. 14. Epub 2012 Mar 20 Feasibility and accuracy of confocal endomicroscopy in comparison with narrow-band imaging and chromoendoscopy for the differentiation of colorectal lesions. Kuiper T, van den Broek FJ, van Eeden S, Fockens P, Dekker E. 5. Gastrointest Endosc. 2007 Nov;66(5):957–65. Epub 2007 Sep 12 Magnifying colonoscopy with narrow band imaging system for the diagnosis of dysplasia in ulcerative colitis: a pilot study. Matsumoto T, Kudo T, Jo Y, Esaki M, Yao T, Iida M.
SSAT/ASCRS JOINT SYMPOSIUM
Endoscopic Evaluation of Dysplasia in Ulcerative Colitis Jeffrey M. Marks
Received: 7 October 2013 / Accepted: 10 March 2014 / Published online: 25 March 2014 # 2014 The Society for Surgery of the Alimentary Tract
Keywords Ulcerative colitis . Endoscopic surveillance . Optical biopsy . Cancer
Ulcerative colitis is a disease which predisposes patients to development of colorectal cancer (CRC). Standard of care in 2012 is surveillance colonoscopy at intervals based on duration of disease and patient age. Presently, multiple biopsies are taken to identify precursors for cancer such as dysplastic cells. Although the actual development of CRC is low, more efficient and effective techniques for identification and surveillance for dysplasia would benefit this population of patients. This brief summary will overview some of the newer endoscopic adjuncts being used in surveillance of ulcerative colitis (UC) and their application. First, there are several assumptions that must be accepted when it comes to the use of surveillance for dysplasia in patients with UC. First, that dysplasia develops initially as a single cell and follows a progression from non-dysplasia to low-grade dysplasia (LGD) to high-grade dysplasia (HGD) to actual CRC. Second, that larger dysplastic fields have been growing for longer and have a higher risk of HGD or CRC, and that taking more random biopsies increases the odds of finding smaller fields of dysplastic cells. The present standard for surveillance includes the technique of four-quadrant biopsies every 10 cm (approx 32 biopsies). This results in approximately 1/2500th of colonic surface area being removed for histologic evaluation. The final assumption is that the finding of HGD on random biopsy is associated with a 40 % risk of
J. M. Marks (*) Department of Surgery, University Hospitals Case Medical Center, 11100 Euclid Ave, Mail Stop LKS 5047, Cleveland, OH 44106, USA e-mail: [email protected]
synchronous CRC and the finding of LGD is associated with a 20 % risk of synchronous CRC. Despite the unclear answers regarding these assumptions and the actual progression of dysplasia to CRC, it has been shown that UC patients undergoing surveillance will have a much lesser risk of dying from CRC than do non-surveyed patients. These standard practices of surveillance endoscopy with routine colonoscopic techniques are being challenged now by the development of enhanced endoscopy which includes c h r o m o e n d o s o c o p y, n a r r o w b a n d i m a g i n g , a n d autoflorescence, all of which have been described to identify foci of dysplasia as small as 2 mm. Probe-based confocal laser endomicroscopy, in pilot studies has been shown to identify aberrant crypt foci (ACF), which may be the earliest recognizable step of transformation in colonic multiphase carcinogenesis.1 In one series, a stepwise increase in the number of ACF from patients with non-dysplasia to dysplasia and then to cancer was identified.2 Univariate and multivariate analyses showed significant correlations between ACF and dysplasia, and the authors proposed an ACF-dysplasiacancer sequence in colitis-associated carcinogenesis similar to the ACF-adenoma-carcinoma sequence in sporadic CRC. Another technique of enhanced endoscopy, autofluorescence (AF) imaging colonoscopy, has also been studied for the detection of dysplastic lesions. However, the rate of positive dysplasia was not statistically different between lesions determined to be low AF (14 %) and those to be high AF (5 %).3 One final mode of enhanced endoscopy, narrow band imaging (NBI), has also been evaluated in a similar manner for detection of dysplasia with lesion patterns being specifically described. In one study that used both conventional endoscopy and NBI, a significant percentage of lesions were
1230
recognized by conventional methods but not NBI, thereby suggesting that both methods would have to be used for the procedure to provide adequate detection of dysplastic lesions.4 In another study evaluating NBI, the positive rate of dysplasia was higher in protruding lesions (2/20 sites, 10 %) than in flat mucosa (3/276 sites, 1.1 %).5 In addition, when the surface pattern was taken into account, the rate of positive dysplasia was higher in a tortuous mucosal pattern (4/50 sites, 8 %) than in the honeycomb-like or villous patterns identified (1/246 sites, 0.4 %). They concluded that the tortuous pattern determined by NBI colonoscopy may be a clue for the identification of dysplasia during surveillance for UC. In conclusion, to date, there is still not a close relation between the conventional endoscopic image and histological assessment of dysplasia in patients with UC undergoing surveillance colonoscopy. Clinical implications of the findings from enhanced endoscopy are not yet available, although they most likely will be in the near future. Therefore, in 2012, standard random biopsies as described above remain the gold standard for surveillance in patients with ulcerative colitis.
J Gastrointest Surg (2014) 18:1229–1230
References 1. Gastroenterol Res Pract. 2012;2012:645173. Epub 2012 Apr 8.Probebased confocal laser endomicroscopy evaluation of colon preneoplastic lesions, with particular attention to the aberrant crypt foci, and comparative assessment with histological features obtained by conventional endoscopy. Mascolo M, Staibano S, Ilardi G, Siano M, Vecchione ML, Esposito D, De Rosa G, De Palma GD. 2. Clin Cancer Res. 2008 Jan 1;14(1):48–54. Aberrant crypt foci as precursors of the dysplasia-carcinoma sequence in patients with ulcerative colitis. Kukitsu T, Takayama T, Miyanishi K, Nobuoka A, Katsuki S, Sato Y, Takimoto R, Matsunaga T, Kato J, Sonoda T, Sakamaki S, Niitsu Y. 3. Colorectal Dis. 2010 Oct;12(10 Online):e291-7. doi: 10.1111/j.14631318.2009.02181.x. Autofluorescence imaging colonoscopy for the detection of dysplastic lesions in ulcerative colitis: a pilot study. Matsumoto T, Nakamura S, Moriyama T, Hirahashi M, Iida M 4. Am J Gastroenterol. 2012 Apr;107(4):543–50. doi: 10.1038/ajg.2012. 14. Epub 2012 Mar 20 Feasibility and accuracy of confocal endomicroscopy in comparison with narrow-band imaging and chromoendoscopy for the differentiation of colorectal lesions. Kuiper T, van den Broek FJ, van Eeden S, Fockens P, Dekker E. 5. Gastrointest Endosc. 2007 Nov;66(5):957–65. Epub 2007 Sep 12 Magnifying colonoscopy with narrow band imaging system for the diagnosis of dysplasia in ulcerative colitis: a pilot study. Matsumoto T, Kudo T, Jo Y, Esaki M, Yao T, Iida M.
