Characteristic submucosal alteration in biliary carcinogenesis of pancreaticobiliary maljunction with a focus on inflammasome activation

Background
This study investigated submucosal alterations in biliary carcinogenesis of pancreaticobiliary maljunction (PBM).
Methods
Thirty-three patients with PBM (including seven with gallbladder [GB] cancer), four with neither biliary tract cancer nor PBM who underwent pancreaticoduodenectomy (controls), and seven with chronic cholecystitis without PBM were enrolled. Protein expression of α-smooth muscle actin (αSMA), CD68, and CD204 in the GB lamina propria and that of NLRP3 and caspase 1 in the GB epithelium and lamina propria were examined.
Results
Compared with the control and cholecystitis groups, αSMA expression was higher in the cancerous part (stroma) of the GB in patients with GB cancer + PBM and in the lamina propria of patients with PBM. The CD204/CD68 ratio in the lamina propria was higher in the PBM group than in the control and cholecystitis groups. NLRP3 and caspase 1 expression in both the lamina propria and epithelium was higher in the PBM than control group. In the PBM group, NLRP3- and caspase 1-positive cells in the lamina propria were located near the epithelium.
Conclusion
Activated fibroblasts and M2 macrophages in the GB lamina propria may be associated with biliary carcinogenesis of PBM, possibly through inflammasome activation.

内容要旨・審査要旨・論文本文の公開
本論文は，著者Shoko Yamashitaの学位論文として提出され，学位審査・授与の対象となっている。

This is the peer reviewed version of the following article: Yamashita, S., Takasu, C.,Morine, Y., Ishibashi, H., Ikemoto, H., Mori, H., Yamada, S., Oya, T., Tsuneyama, K., Shimada, M., (2022), Characteristic submucosal alteration in biliary carcinogenesis of pancreaticobiliary maljunction with a focus on inflammasome activation. Journal of Hepato-Biliary-Pancreatic Sciences, 30, 4, 462-472., which has been published in final form at https://doi.org/10.1002/jhbp.1253. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.