Unresolved questions of chromocholangioscopy with methylene blue

We have read the article of Hoffman et al. with interest [1]. They reported usefulness of chromocholangioscopy with methylene blue [1]. In the article, the authors state that their study is the first to use chromocholangioscopy with methylene blue. However, we have already reported a paper with the same concept in 1996 [2], although we assessed this issue by percutaneous cholangioscopy. In our paper, we clearly mentioned the difference of methylene blue staining properties based on types of biliary epithelia: normal, metaplasia, or cancer. The cancerous epithelia stained significantly less often than either the normal (P < 0.000005) or the metaplastic (P < 0.001) epithelia [2] according to our study using frozen sections of biopsied specimens. In addition, our investigation revealed that this stain was truly absorbed by biliary epithelium [2]. The paper written by Hoffman et al. [1] concluded that methylene-blue-aided cholangioscopy was beneficial in order to guess which epithelia is lining the surface of the bile duct, which is similar to our findings.

Further, to confirm that biliary epithelium is stained by methylene blue as equally as intestinal epithelium, gastric intestinal metaplasia, or specialized intestinal metaplasia of Barrett’s esophagus [3], we assessed microscopically the methylene blue staining properties using frozen sections taken from the bile duct. These findings were then compared with endoscopic findings and it was proven that endoscopic findings were sometimes different from microscopic findings [2]. In other words, blue-colored epithelium visible by chromocholangioscopy is not always epithelium truly stained by methylene blue. Moreover, our results suggest that methylene blue may adhere to mucus or exudate on the surface of the biliary epithelium. Under these circumstances, the mucus or exudate may disturb the contact of methylene blue with the superficial epithelia. Mucus or exudate is usually seen in the bile duct, especially in patients with cholangiocarcinoma or inflammatory diseases such as primary sclerosing cholangitis. For these disorders, we may miscalculate methylene blue staining patterns or properties of the biliary epithelium. Removal of the superficial exudate will therefore help to accurately evaluate the methylene blue staining properties of biliary epithelia. If the issue is to be resolved, chromocholangioscopy with methylene blue would be a more promising modality to define malignancies and to clarify the boundary of superficial lateral spread of cholangiocarcinoma ([Fig. 1] and [Fig. 2]).

Competing interests: None

Fig. 1 Percutaneous transhepatic cholangioscopy showing indistinct yellowish area adjacent to the obstruction due to cholangiocarcinoma.

Fig. 2 This yellowish area remained unstained even after using methylene blue. Chromocholangioscopy was helpful to clearly indicate the boundary of superficial lateral spread of cholangiocarcinoma.

References

• 1 Hoffman A, Kiesslich R, Bittinger F. et al . Methylene-blue-aided cholangioscopy in patients with biliary strictures: feasibility and outcome analysis.  Endoscopy. 2008;  Apr 11: DOI: 10.1055/s-2007-995688
• 2 Maetani I, Ogawa S, Sato M. et al . Lack of methylene blue staining in superficial epithelia as a possible marker for superficial lateral spread of bile duct cancer.  Diagn Ther Endosc. 1996;  3 29-34
• 3 Horwhat J D, Maydonovitch C L, Ramos F. et al . A randomized comparison of methylene blue-directed biopsy versus conventional four-quadrant biopsy for the detection of intestinal metaplasia and dysplasia in patients with long-segment Barrett's esophagus.  Am J Gastroenterol. 2008;  103 546-554