Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.
The study by Hurlstone and colleagues (Gut 2004;53:376–80) is commendable in raising the awareness of flat and depressed colonic neoplasia. However, I am surprised at the high rate of severe dysplasia reported in their study. Of their 170 lesions, 19% harboured high grade dysplasia. This high rate of severe dysplasia is particularly surprising as the study reported on diminutive colorectal lesions.
Large numbers of small adenomas develop as we grow older. According to autopsy studies, over 30% of the population over the age of 50 years have small adenomas.1 With the use of dye spraying and magnification, these lesions can be found in up to 50% of asymptomatic patients attending for colonoscopy.2 As only 5% of the population develop colorectal cancer, clearly the great majority of small adenomas never grow, advance, or turn cancerous. This conclusion is supported by studies reporting a lower than 1% risk of high grade dysplasia in small adenomas.3–5
Further studies have reported on the risk of high grade dysplasia in adenomas of all sizes. In our own series from Leeds,6 high grade dysplasia was found in 9.5% of neoplastic lesions of all size ranges. Similarly, Tsuda and colleagues7 reporting on colorectal adenomas in Sweden found high grade dysplasia in an average of 7.8% of lesions. Saitoh and colleagues8 reported on neoplasia in a North American population and found high grade dysplasia in 9% of all lesions. Konishi and colleagues9 published the findings from the University Hospital in Tokyo and reported high grade dysplasia in 10.1% of adenomas. The corresponding value from the National Cancer centre in Tokyo(personal communication) is high grade dysplasia in 10.4% of all neoplastic lesions (excluding invasive cancers). Kiesslich and colleagues10 reported a 7.5% risk of high grade dysplasia in a German population. In all studies, the risk of high grade dysplasia increased with the size of the lesion.
If Hurlstone et al are correct in their conclusion that one in five diminutive adenomas harbour early cancer, we face the huge task of harvesting all colonic lesions. If their findings are incorrect, the reader who attempts to remove all small colonic polyps will be wasting time, resources, and putting patients at risk unnecessarily.
We thank Dr Rembacken for his interest in our paper and agree with his observation regarding the high prevalence of high grade dysplasia (HGD) in the study cohort (Gut 2004;53:376–80). Multiple factors may account for this finding. Importantly, case mix in comparable studies is variable. Our study cohort included 233 patients (90%) who were undergoing colonoscopy for polyp surveillance, post surgical cancer surveillance, or investigation of iron deficiency anaemia. This cohort is markedly different to that of the initial Leeds prevalence study1 and that of Saito’s group2 who included only 22% of patients with a previous history of colorectal polyps but did not include patients undergoing postoperative surgical surveillance or those with suspected colorectal neoplasia. Additionally, patients with hereditary non-polyposis colon cancer were excluded from the analysis in both Jaramillo’s3 and Tsuda’s4 study. Our cohort included four patients who fulfilled modified Amsterdam criteria for hereditary non-polyposis colon cancer syndrome, all of which were germline mutation positive. This is a high risk colorectal cancer group who are known to develop flat right hemicolonic lesions, which may favour a de novo neoplastic pathway and demonstrate early submucosal invasion despite diminutive luminal appearances.5–7 Thirty per cent of diminutive adenomas with foci of HGD were identified in this group.
Chromoscopic techniques used also vary between studies and may alter detection of diminutive and flat colorectal lesions. In the studies of Rembacken and colleagues,1 Jaramillo and colleagues,3 and Tsuda and colleagues,4 selective chromoscopy was used following detection of subtle mucosal changes. Such techniques may fail to diagnose some diminutive lesions, which rarely demonstrate the characteristics of fold convergence, focal vascular net loss, or other focal mucosal architectural changes.8 Furthermore, Saito’s chromoscopic method differed significantly from that of our design where all patients received mucosal chromoscopy of the left colon with progression to pan-mucosal chromoscopy only if left sided lesions were apparent.2 Hence flat adenomas and carcinomas that are known to cluster within the right hemicolon and may not be associated with synchronous left sided lesions could have been underrepresented using this study design.9,10 Furthermore, Mitooka’s study design differed again using ingested indigo carmine dye capsules.11
Dr Rembacken is however correct to conclude that resection of all diminutive and flat colorectal lesions are not required. In our study, although increasing the total number of adenomas detected, a significant number of hyperplastic lesions were detected using pan-chromoscopy, with 86% being present within the rectosigmoid. These data confirm the observation of Brooker and colleagues12 and indeed that of our initial prevalence study9 where 93% of flat hyperplastic lesions were present in the left colon.
High magnification chromoscopic colonoscopy has also been shown by our group and others to have a high sensitivity and specificity at differentiating between hyperplastic lesions and adenomas.13–16 Hence the additional use of magnification chromoscopy may lower the histopathological burden of insignificant biopsies and attenuate overall procedure related risk by excluding insignificant lesions from inappropriate endoscopic resection.
In conclusion, pan-chromoscopic colonoscopy versus targeted chromoscopy proved beneficial in our randomised controlled trial using a cohort of patients assuming a high risk of colorectal neoplasia and may help better stratify overall colorectal cancer risk in this group. Kiesslich et al, using pan-chromoscopy for the detection of intraepithelial neoplasia in longstanding chronic ulcerative colitis, have noted similar observations,17 data validated by our group.18 The implications of these data are therefore significant as interval cancers are known to occur despite intensive colonoscopic follow up.19,20 No data exist regarding the applicability of this technique when used in the setting of diagnostic colonoscopy in low-moderate risk colorectal cancer cohorts. Further studies are required to assess the efficacy of chromoscopy as an adjunctive endoscopic tool in this group. This is particularly relevant given the imminent introduction of a Nationwide Colorectal Cancer Screening Programme in the UK where economic, endoscopic, histopathological, and man power issues are scarce but pivotal to a successful programme.