Capítulo 2.- Técnicas Experimentales
2.3. Técnicas de caracterización estructural
2.3.1. Difracción de rayos X
In the NBI arm, 1348 random biopsies were taken (mean per patient, n=25, SD 6.3) and histopathology revealed low-grade dysplasia in 1 biopsy (from 1 patient). This patient had a dysplastic lesion already detected by targeted biopsies in ascending colon (random biopsies detected dysplasia in sigmoid colon). However, no further dysplastic lesions were detected in this patient during 4 years of colonoscopic surveillance. During withdrawal with WLE, 1359 random biopsies were taken (mean
3.4 Discussion
This is the third randomized, but the first parallel group, multi-centre study comparing WLE and NBI for detection of dysplasia in patients with long standing ulcerative colitis.
The results of this study show that using NBI does not appear to lead to higher
This is in agreement with two other studies published on the use of NBI in dysplasia detection in UC. Although the other two studies used a different methodology of delayed cross over design, they both showed no increase in detection of dysplasia when using NBI. The first study (106) attributed the lack of improved detection with NBI to the fact that a first generation prototype NBI was used which provided reduced light intensity leading to a darker image, insufficient to obtain a good overview of mucosal surface. The second study by the same group (154) compared new generation NBI with high definition white light colonoscopy and again could not demonstrate improved dysplasia detection with NBI. However both of these studies found a much higher rate of dysplasia when using white light alone (17-19%) compared to dysplasia detection rates found in the older chromoendoscopy studies (7.5%) (91). As the inclusion criteria for chromoendoscopy and NBI studies, including our own, were similar, this high rate of dysplasia detection is likely to be attributed to the improved resolution obtained with modern conventional white light colonoscopy.
The prevalence of dysplasia in our study of 9% in both arms is more comparable to the historical data. Our original inclusion criteria aimed to identify high-risk patients more likely to have dysplasia, however due to slow recruitment this inclusion criterium was abolished after 40 patients were recruited. Therefore patients finally included in the study fulfilled the same criteria as those in previously published studies (106, 154).
Factors such as duration of the disease, previous history of dysplasia, family history of CRC and primary sclerosing cholangitis have been associated with increased risk of dysplasia in patients with UC whereas the use of maintenance mesalazine has been found to reduce the risk of dysplasia (155, 156). In this study there was no
difference between the two arms with regards to increased risk factors for dysplasia and furthermore no difference in the primary outcome when data were adjusted for withdrawal time, family history of CRC or a previous history of dysplasia.
Most national guidelines on surveillance colonoscopy for patients with long standing ulcerative colitis recommend that quadrantic random biopsies should be taken every 10cm to improve detection of dysplasia. The most recent guideline from British Society of Gastroenterology (112) advises the use of chromoendoscopy with targeted biopsies as the preferred method of surveillance although if not available the usual random biopsies should be taken. The yield of dysplasia from random non-targeted biopsies in this study was 0.04% and the only random biopsy that showed low grade dysplasia was detected in the patient who already had a dysplastic lesion detected with a targeted biopsy. In addition, the long-term outcome of low grade dysplasia on a single biopsy in ulcerative colitis is not clear and indeed this patient had no further dysplasia detected during 4 years of colonoscopic surveillance. This level of dysplasia detection is low enough that serious consideration should be given to abandoning non-targeted random biopsies in patients with ulcerative colitis.
This study has a number of limitations. NBI was compared to white light endoscopy and not chromoendoscopy, which many national guidelines now recommend as the gold standard surveillance strategy. However the dysplasia detection achieved with white light in this study is comparable to that historically achieved when using chromoendoscopy, suggesting an effect of improved resolution of standard white light colonoscopy.
Power calculation for a parallel, randomized controlled trial necessitated inclusion of a large number of subjects, but a priori decision was made to stop the trial early if assumptions of power calculation were not met. At half-way point there was no difference in dysplasia detection between WLE and NBI, with OR 0.69 (95% CI 0.16-2.96) suggesting that NBI was less likely to detect dysplasia than WLE with confidence intervals that were less than 3, which was the basis of original power calculation. Further recruitment would have been unlikely to detect the differences as specified in the original power calculation, although a smaller difference may have
Although NBI is unlikely to have a role in dysplasia detection, it may aid lesion characterization, when combined with other imaging tools to aid the detection (eg, AFI), decreasing the number of false positive findings (157). Other narrow spectrum technologies such as FICE and iSCAN have not been formally studied in this setting but like NBI are unlikely to lead to improved detection of dysplasia. High definition white light may in fact be as good as chromoendoscopy and warrants a formal comparative study.
In conclusion, this, albeit, underpowered study, could not demonstrate improved dysplasia detection as specified in the power calculation by using NBI when compared to conventional white light colonoscopy. Further work should compare NBI with chromoendoscopy for detection of dysplasia using randomised, cross-over, back-to-back study design.