Introduction
Chromoendoscopy improves the visualization and differentiation of mucosal structures and enhances the polyp and adenoma detection rates. The dye-spray technique is a lengthy and laborious procedure. An oral formulation could serve as alternative, as demonstrated by Methylene Blue MMX. In contrast to methylene blue, patent blue V (E131) is an EFSA-approved food dye and practically free of side effects.
Aims & Methods
The aim of our case series was to encapsulate patent blue V in shellac food-grade microcapsules for oral intake and to evaluate the delayed release and mucosal staining as proof of principle.
Capsules filled with shellac microcapsules containing 100 mg patent blue V were produced by food technology for pH-dependent release in the ileum.
Between December 2016 and March 2022, 37 patients scheduled for a chromocolonoscopy volunteered to receive oral microcapsules for staining instead of the conventional dye-spraying procedure. 20 of the patients were additionally scheduled for a gastroscopy. Patients self-administered 4 capsules during the second half of the bowel preparation with KleanPrep (Norgine), at the latest 5 hours before chromocolonoscopy. Staining was rated by a score (0 points = not stained, 4 points = optimal even staining).
Results
The best staining quality was observed between the cecum and the sigmoid (ranges between 3.3 and 3.6 points). The terminal ileum (2.9 points) and rectum (3.1 points) were also stained acceptable. Absence of staining or overstaining were not reported. The mucosa in the upper gastrointestinal tract was not stained (0 points) in patients who underwent a gastroscopy on the same day. The polyp detection rate in our cohort was approximately 64%, the adenoma detection rate was 56%. The patent blue V capsules produced a good staining intensity, contrast of lesions, polyps and adenomas. The staining quality was rated equivalent to experience with dye-spraying chromocolonoscopy, with the advantage of clean equipment and a reduction of colonoscopy time.
Conclusion
Patent blue V microcapsules produced an even staining of the mucosal surface for chromocolonoscopy. Delayed-release patent blue V may be a superior and safe alternative to dye-spray techniques and Methylene Blue MMX with potential advantages in time of the procedure, sedation, cleaning, costs and skills. After this proof of concept, a randomized study with delayed-release patent blue V appears warranted.
References
1. Aziz M, Haghbin H, Sayeh W, et al. Comparison of Artificial Intelligence With Other Interventions to Improve Adenoma Detection Rate for Colonoscopy: A Network Meta-analysis. J Clin Gastroenterol 2022.
2. Repici A, Wallace MB, East JE, et al. Efficacy of Per-oral Methylene Blue Formulation for Screening Colonoscopy. Gastroenterology 2019;156:2198-2207.e1.
3. Fernando Aguilar, Riccardo Crebelli, Birgit Dusemund, Pierre Galtier, John Gilbert, David Gott, Ursula Gundert-Remy, Juergen König, Claude Lambré, Jean-Charles Leblanc, Alicja Mortensen, Pasquale Mosesso, Dominique Parent-Massin, Ivan Stankovic, Paul Tobb RAW and MW. Scientific Opinion on the re-evaluation of Patent Blue V (E 131) as a food additive. EFSA J 2013.
4. Theismann E-M, Keppler JK, Knipp J-R, et al. Adjustment of triple shellac coating for precise release of bioactive substances with different physico-chemical properties in the ileocolonic region. Int J Pharm 2019;564:472–484.
Disclosure
European patent No. 3445336; GW, EMT, JK, KS, SS, ME are listed as inventors
GHW is employed part-time by CONARIS Research Institute AG (Kiel, Germany).
SS reports consulting fees from Ferring