Surgical therapies for iatrogenic bile duct lesions (IBDL) – review

Background: Primary biliary cholangitis (PBC) is characterized by a high prevalence of serum anti-mitochondrial antibodies against the E2 subunit of the pyruvate dehydrogenase complex and bile duct lesions called chronic non-suppurative destructive cholangitis (CNSDC) in small bile ducts, eventually followed by extensive bile duct loss and biliary cirrhosis. Macroautophagy (a major type of autophagy) is a process of cellular self-digestion that plays a critical role in energy homeostasis and in the cytoprotection to various stresses. Deregulated autophagy is thought to be associated with various human diseases. Key Messages: Accumulating evidences suggest that deregulated autophagy may be a central player in the pathogenesis of PBC. Damaged cholangiocytes involved in CNSDC show vesicular expression of autophagy marker LC3 and accumulation of p62/sequestosome-1, suggesting deregulated autophagy. Deregulated autophagy may be involved in the autoimmune process via the abnormal expression of mitochondrial antigens and also in cholangiocyte senescence in bile duct lesions in PBC. In vitro study showed that hydrophobic bile acids, such as glycochenodeoxycholic acid (GCDC), as well as serum deprivation and oxidative stress, cause autophagy, deregulated autophagy and abnormal expression of mitochondrial antigens followed by cellular senescence in cholangiocytes. Although exact mechanisms of deregulated autophagy remain to be clarified, endoplasmic reticulum (ER) stress may be a plausible cause of deregulated autophagy induced by GCDC in cholangiocytes. Impaired ‘biliary bicarbonate umbrella' may further exacerbate the toxicity of GCDC to cholangiocytes. Interestingly, pretreatment with ursodeoxycholic acid (UDCA) and tauro-UDCA, which is a chemical chaperone enhancing the adaptive capacity of the ER, significantly suppressed ER stress, deregulated autophagy and cellular senescence induced by GCDC and other stresses in cholangiocytes. Conclusions: GCDC may play a role in the occurrence of deregulated autophagy and cellular senescence at least partly through the induction of ER stress in PBC. Deregulated autophagy and cellular senescence can be a promising therapeutic target in PBC.

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S1312 Ultrasonographic Imaging of Bile Duct Lesions in Autoimmune Pancreatitis

Gastroenterology ◽

10.1016/s0016-5085(08)61033-1 ◽

2008 ◽

Vol 134 (4) ◽

pp. A-224

Author(s):

Rikako Koyama ◽

Yuko Koizumi ◽

Tsunao Imamura ◽

Chikao Okuda ◽

Kazuo Takeuchi

Keyword(s):

Bile Duct ◽

Autoimmune Pancreatitis ◽

Bile Duct Lesions

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What Are the Precursor and Early Lesions of Peripheral Intrahepatic Cholangiocarcinoma?

International Journal of Hepatology ◽

10.1155/2014/805973 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 30

Author(s):

Yasuni Nakanuma ◽

Akemi Tsutsui ◽

Xiang Shan Ren ◽

Kenichi Harada ◽

Yasunori Sato ◽

...

Keyword(s):

Bile Duct ◽

Bile Ducts ◽

Precursor Lesions ◽

Intraductal Papillary Neoplasm ◽

Combined Hepatocellular Cholangiocarcinoma ◽

Biliary Adenofibroma ◽

Bile Duct Lesions ◽

Large Bile Duct ◽

Papillary Neoplasm ◽

Bile Duct Adenoma

Cholangiocarcinoma (CC) is divided into distal, perihilar, and intrahepatic CCs (ICCS), and are further subdivided into large bile duct ICC and peripheral ICC. In distal and perihilar CC and large duct ICC, biliary intraepithelial neoplasm (BilIN) and intraductal papillary neoplasm (IPN) have been proposed as precursor lesions. Peripheral ICC, bile duct adenoma (BDA), biliary adenofibroma (BAF), and von Meyenburg complexes (VMCs) are reportedly followed by development of ICCs. Herein, we surveyed these candidate precursor lesions in the background liver of 37 cases of peripheral ICC and controls (perihilar CC, 34 cases; hepatocellular carcinoma, 34 cases and combined hepatocellular cholangiocarcinoma, 25 cases). In the background liver of peripheral ICC, BDA and BAF were not found, but there were not infrequently foci of BDA-like lesions and atypical bile duct lesions involving small bile ducts (32.4% and 10.8%, resp.). VMCs were equally found in peripheral CCs and also control CCs. In conclusion, BDA, BAF, and VMCs are a possible precursor lesion of a minority of peripheral CCs, and BDA-like lesions and atypical bile duct lesions involving small bile ducts may also be related to the development of peripheral ICC. Further pathologic studies on these lesions are warranted for analysis of development of peripheral ICCs.

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