Dear Editor

We thank Saito and colleagues for their interest in our recent paper that prospectively examined the safety and efficacy of high magnification chromoscopic colonoscopy for the diagnosis of neoplasia in flat and depressed lesion of the colorectum.[1]

Their abstract data,[2] using the modified Paris classification of superficial neoplastic lesions [3] as determined by the newly designated 1000m vertical mucosal extension limit, offers impressive sensitivity and overall accuracy rates when distinguishing sm1 from sm2 invasion. We look forward to publication of the full manuscript soon.

However, fundamental differences still exist between Japanese and Western histopathologists that make comparative studies between East and West difficult.[4] Our histopathology was interpreted using the Vienna classification of gastrointestinal epithelial neoplasia as proposed by Schlemper et al. following the consensus classification workshop.[5] The consensus terminology differentiates non-invasive low-grade neoplasia, non-invasive high-grade neoplasia (which includes suspicion of invasive neoplasia) and invasive neoplasia (intra-mucosal carcinoma, submucosal carcinoma or beyond) into Vienna categories 3,4 and 5 respectively.[5] Hence in table 4[1] our neoplastic invasive group includes both Vienna 4 and 5 lesions together. This ‘collection’ of data reflects current histopathological practice in the UK where sm invasion rates (1-3) are not routinely specified. While we accept that the modified Paris guidelines [3] are extremely helpful, our current practice is aimed at overall patient ‘risk stratification’ where the natural history of LGD has yet to be determined but that of HGD is more defined; assuming a high risk of progression to invasive neoplasia6. Differentiation of hyperplastic (non-neoplastic / non-invasive) from LGD adenoma (neoplastic / non- invasive) therefore still remains an important asset to the endoscopists (sensitivity 98% / specificity 92% in our series), as the number of inappropriate biopsies and resections can be safely limited while allowing for appropriate risk stratification permitting suitable colonoscopic follow-up intervals.[7]

We agree with the data of Tanaka and Tsuruta et al. who have demonstrated that sm superficial lesions without lymphovascular invasion or poorly differentiated histological features have a low incidence of local nodal metastasis. These data are currently in press.[8]

While we acknowledge the concerns raised by Saito et al, we feel that despite adopting the Paris guidelines’ our data still provides a comprehensive guide to HMCC as is practiced within the UK.

References

1. Hurlstone DP, Cross SS, Adam I, Shorthouse AJ, Brown S, Sanders DS, Lobo AJ. Efficacy of high magnification chromoscopic colonoscopy for the diagnosis of neoplasia in flat and depressed lesions of the colorectum: a prospective analysis. Gut 2004;53:284-290.

2. Matsuda T, Fujii T, Ono A. Effectiveness of magnifying colonoscopy in diagnosing the depth of invasion of colorectal neoplastic lesions: invasive pattern is an indication for surgical treatment. Gastrointest Endosc 2003;575:AB176.

3. Paris Workshop Participants. The Paris endoscopic classification of superficial neoplastic lesions: Esophagus, stomach and colon. Gastrointest Endosc 2002;58:S3-43.

4. Schlemper RJ, Itabashi M, Kato Y, Lewin KJ, Riddell RH, Shimoda T, Sipponen P, Stolte M, Watanabe H. Differences in the diagnostic criteria used by Japanese and Western pathologists to diagnose colorectal carcinoma. Cancer 1998;82:60-69.

5. Schlemper RJ, Riddell RH, Kato Y, Borchard F, Cooper HS, Dawsey SM, Dixon MF, Fenoglio-Preiser CM, Flejou JF, Geboes K, Hirota T, Itabashi M, Iwafuchi M, Kim YI, Kirchner T, Klimpfinger M, Koike M, Lauwers GY, Lewin KJ, Oberhuber G, Price AB, Rubio CA, Shimoda T, Sipponen P, Stolte M, Watanabe H, Yamabe H. The Vienna classification of gastrointestinal neoplasia. Gut 2000;47:251-255.

6. Ponz de Leon M, Di Gregorio C. Pathology of colorectal cancer. Dig Liver Dis 2001;33:372-388.

7. Hurlstone DP, Cross SS, Slater R, Sanders DS, Brown S. Detecting diminutive colorectal lesions at colonoscopy: a randomised controlled trial of pan-colonic versus targeted chromoscopy. Gut 2004;53:376- 380.

8. Hurlstone DP, Cross SS, Adam I, Shorthouse AJ, Brown S, Sanders DS, Lobo AJ. An evaluation of colorectal endoscopic mucosal resection using high-magnification chromoscopic colonoscopy: a prospective study of 1000 colonoscopies. Endoscopy 2003:in press.

Dear Editor

We read with great interest the recent article by Hurlstone et al.[1] in applying the clinical classification of pit pattern (non-invasive or invasive) originally described by Fujii [2,3] to discriminate between adenoma with low grade dysplasia (LGD), adenoma with high grade dysplasia (HGD) and beyond. The authors reported the poor sensitivity (50%) of high- magnification chromoendoscopy to differentiate non-invasive from invasive pit pattern in adenoma (HGD) and beyond. Since these are crucial clinical concepts, we would like to take some exception to the authors' interpretation of the data.

First, there is growing evidence to support that submucosal (sm) superficial lesions without lymphovascular invasion or poorly differentiated components do not have lymph node metastases [4-6]. As a result, the recent Paris endoscopic classification of superficial neoplastic lesions determined 1000µm as the appropriate cut-off limit between sm1 and sm2 lesions.[7] In this regard, the nature of the pit pattern has been used to ascertain the depth of sm invasion in order to determine whether endoscopic resection or surgery is the ideal treatment.

In fact, the clinical classification of pit pattern proved to be effective in our large prospective series in differentiating intramucosal or sm superficial invasion (sm1: less than 1000µm) from sm deep invasion (sm2: more than 1000µm). In this study, histopathology confirmed epithelial neoplasia in 98% of the 2951 lesions with a non-invasive pattern and sm deep invasion in 86% of the 156 lesions with an invasive pattern. In addition, the calculated sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 85%, 99%, 86%, 99%, and 99%, respectively, in differentiating intramucosal or sm superficial invasion (sm1) from sm deep invasion (sm2) [8] In relation to the authors' data analysis, we sympathize with the reported accuracy of high-magnification chromoendoscopy in discriminating neoplastic from non- neoplastic lesions, however we do not agree with their subgroup analysis of pit patterns according to the non-invasive and invasive types as shown in Table 4 of the article. It appears that significant information and analysis of sm1 and sm2 cases are missing. The authors seem to have at least partly mistaken the utility of the pit pattern clinical classification in trying to differentiate adenoma (LGD) from intramucosal carcinoma, which is therapeutically unnecessary because endoscopic resection is the standard treatment for both kinds of lesions. More importantly, they arbitrarily grouped adenoma (HGD), intramucosal and sm carcinomas in one group (n=141) instead of differentiating intramucosal and sm1 from sm2 carcinomas, which is fundamental in determining the proper therapeutic strategy.

In conclusion, we believe that the reported poor sensitivity of high- magnification chromoendoscopy in this study is due to an inappropriate application of the clinical classification of pit pattern. The misuse of this clinical concept has adversely affected the results and recommendations of the authors (cold biopsy or 20 MHz ultrasound mini probe for lesions with a depressed component and a type IIIs/V pit pattern).

References

1. D P Hurlstone, S S Cross, I Adam, et al. Efficacy of high magnification chromoscopic colonoscopy for the diagnosis of neoplasia in flat and depressed lesions of the colorectum: a prospective analysis. Gut 2004; 53:284-290.

2. Fujii T, Hasegawa T, Saitoh Y, et al. Chromoscopy during colonoscopy. Endoscopy 2001; 33:1036-41.

3. Kato S, Fujii T, Koba I, et al. Assessment of colorectal lesions using magnifying colonoscopy and mucosal dye spraying: can significant lesions be distinguished? Endoscopy 2001; 33:306-10.

4. Tanaka S, Haruma K, Oh-E H, et al. Conditions of curability after endoscopic resection for colorectal carcinoma with submucosally massive invasion. Oncol Rep. 2000; 7:783-88.

5. Tsuruta O, Toyonaga A, Ikeda H, et al. Clinicopathological study of superficial-type invasive carcinoma of the colorectum: special reference to lymph node metastasis. Int J Oncol. 1997;10:1003-8.

6. Nishi M, Moriyasu F. Clinicopathological study for reevaluation of the depth of submucosal invasion and histological classification of early colorectal cancer. Nippon Shokakibyo Gakkai Zasshi 2002;99:769-778. [In Japanese with English abstract.]

7. Participants in the Paris Workshop. The Paris endoscopic classification of superficial neoplastic lesions: Esophagus, stomach, and colon. November 30 to December 1, 2002. Gastrointest Endosc. 2003;58:S3- 43.

8. Matsuda T, Fujii T, Ono A, et al. Effectiveness of magnifying colonoscopy in diagnosing the depth of invasion of colorectal neoplastic lesions: invasive pattern is an indication for surgical treatment. [Abstract.] Gastrointest Endosc. 2003;575:AB176.