Altered Bile Composition in the Gallbladder and Common Bile Duct of Patients with Anomalous Pancreaticobiliary Ductal Junction

Sugiyama, Yuzuru; Kobori, Hiroyasu; Hakamada, Kenichi; Seito, Dai; Sasaki, Makoto

doi:10.1007/s002689910004

Cited by 34 publications

(26 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[1][2][3] PBM is defined as the union of the pancreatic and common bile ducts outside the wall of the duodenum, beyond the influence of the sphincter of Oddi. [3][4][5][6][7] Normally, the pancreaticobiliary duct and junction are governed by sphincter, but as a result of the anomaly, pancreatic juice can reflex into the common bile duct. PBM patients are known to be associated with bile duct dilatation and also biliary tract carcinoma, especially in the Far East.…”

mentioning

confidence: 99%

“…PBM patients are known to be associated with bile duct dilatation and also biliary tract carcinoma, especially in the Far East. [3][4][5][6][7] Patients who develop gallbladder carcinoma in association with PBM are usually 10 years younger than those without PBM. Synchronous primary cancers of the gallbladder and common bile duct have also been associated with PBM.…”

mentioning

confidence: 99%

“…[3][4][5] It has been postulated in PBM that the reflex of pancreatic juice into the common bile duct and the stagnation of pancreatic juice mixed with bile have been considered to play an important role in the pathophysiology of PBM, including biliary tract carcinoma. [3][4][5][6][7][8][9][10] A high concentration of lysolecithin (LL) was reported in the gallbladder bile of PBM, [3][4][5][6][7] and LL is produced from lecithin by activated phospholipase A2 in the refluxing pancreatic juice in PBM. LL and other altered bile components may be responsible for the development of PHP and also carcinoma of the gallbladder in PBM.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Papillary hyperplasia of the gallbladder in pancreaticobiliary maljunction represents a senescence-related lesion induced by lysolecithin

Yamaguchi

Sasaki

Harada

et al. 2009

Laboratory Investigation

View full text Add to dashboard Cite

Cellular senescence, an irreversible growth arrest, is considered to play as safeguard against malignant progression, though such a mechanism is speculative in human carcinogenesis. In gallbladder carcinoma, cholecystolithiasis and pancreaticobiliary maljunction (PBM) are major risk factors. Here, by using 113 surgically resected gallbladders and cultures of human gallbladder epithelial cells (HGECs) and gallbladder carcinoma cell line (TGBC2TKB), we examined carcinogenesis with respect to cellular senescence. Among 15 cases of PBM in which carcinoma was found in 4 cases, nonneoplastic gallbladder mucosa showed diffuse papillary hyperplasia (PHP). PHP was not found in gallbladders with cholecystolithiasis. Interestingly, PHP exhibited senescent features such as expression of p16INK4A and low cell proliferative activity. In contrast, EZH2, a polycomb group protein, was overexpressed in intraepithelial neoplasm and carcinoma in gallbladders with cholecystolithiasis. In PBM, EZH2 was expressed only in carcinoma foci but not in PHP. Cultured HGECs treated with lysolecithin, the level of which is elevated in gallbladder bile of PBM, showed increased expression of p16INK4A and senescence-associated b-galactosidase. Conversely, enforced overexpression of EZH2 in senescent HGECs reduced p16 INK4A expression. A knockdown of EZH2 in cultured TGBC2TKB cells increased p16 INK4aexpression. In conclusion, PHP in PBM may act as a barrier to malignant transformation for decades. EZH2 may be responsible for the escape from cellular senescence followed by malignant transformation in the gallbladder of PBM.

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Papillary hyperplasia of the gallbladder in pancreaticobiliary maljunction represents a senescence-related lesion induced by lysolecithin

Yamaguchi

Sasaki

Harada

et al. 2009

Laboratory Investigation

View full text Add to dashboard Cite

show abstract

“…Sugiyama [25] had suggested that elevation of the lysolecithin (LL) in the bile was one of the factors for development of biliary tract carcinoma in patients with APBDU: the LL in the phospholipid produced from lecithin by activated phospholipase A 2 in the refluxed pancreatic juice, was significantly elevated in the APBDU group. Yoon [26] also indicated that bile acids induced both EGFR phosphorylation and enhanced COX-2 protein expression.…”

Section: Discussionmentioning

confidence: 99%

Bile from a patient with anomalous pancreaticobiliary ductal union promotes the proliferation of human cholangiocarcinoma cellsviaCOX-2 pathway

Zou²,

Liu³

et al. 2003

WJG

View full text Add to dashboard Cite

AIM:To explore the effects of COX-2 gene in the proliferative activity induced by bile from anomalous pancreaticobiliary ductal union (APBDU) on human cholangiocarcinoma cell line. METHODS:Bile sample from APBDU and normal bile sample were used for this study. The proliferative effect of bile was measured by methabenzthiazuron (MTT) assay; COX-2 mRNA was examined by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). Cell cycle was analyzed by flow cytometry (FCM), and the PGE 2 levels in the supernatant of cultured cholangiocarcinoma cells were quantitated by enzyme-linked immunoabsordent assay (ELISA). RESULTS:Bile from APBDU can significantly promote the proliferation of human cholangiocarcinoma QBC939 cells compared with normal bile (P=0.005) and upregulated remarkably their COX-2 mRNA expression (P=0.004). The proliferative activity of APBDU bile can be abolished by addition of cyclooxygenase-2 specific inhibitor celecoxib. CONCLUSION:Bile from APBDU can promote the proliferation of human cholangiocarcinoma QBC939 cells via COX-2 pathway.Wu GS, Zou SQ, Liu ZR, Wang DY. Bile from a patient with anomalous pancreaticobiliary ductal union promotes the proliferation of human cholangiocarcinoma cells via COX-2 pathway.

show abstract

“…These bacteriadegraded bile acids also present in the gastric aspirate from remote postgastrectomy patients though consisting of a small portion of the whole reflux bile acids. Secondly, lysophosphatidylcholine (lysoPC), the product of phosphatidylcholine hydrolysis by phospholipase A2, has been suggested to play a role in the pathogenesis of gallbaldder cancer in the APBDJ (Anomalous Pancreaticobiliary Ductal Junction) patients [47] . LysoPC might also be produced in the stump stomach due to the reflux juice containing aberrant pancreatic juice and bile.…”

Section: Discussionmentioning

confidence: 99%

Carcinogenic potential of duodenal reflux juice from patients with long-standing postgastrectomy

Wang²,

Zhang³

et al. 2001

WJG

View full text Add to dashboard Cite

AIM To determine whether study on the carcinogenic potential of reflux juice from patients with remote gastrectomy could clarify the inherent relationship between duodenal reflux and gastric stump cancer. METHODS A total of 37 reflux juice samples (13 BillrothI, 24 BillrothII) were employed in the present study. A two-stage transformation assay using BALB/c 3T3 cells was carried out to test the initiating or promoting activity of these samples. RESULTS Two of 18 (11.1%) reflux samples exerted initiating activities, whereas 9/19 (47. 4%) samples enhanced the MNNG-initiating cell transformation, suggesting the duodenal reflux juice might more frequently possess the tumorpromoter activity (P = 0.029). In addition, there was no difference in initiating activities of the samples irrespective of surgical procedures (P = 0.488), while Billroth II samples exhibited stronger tumor-promoter activity than Billroth I samples (P = 0.027). Furthermore, the promoter activities were well correlated with the histological changes of the stomas (r s = 0.625, P = 0.004), but neither their cytotoxicities nor initiating activities had this correlation (Probabilities were 0.523 and 0.085, respectively

show abstract

Altered Bile Composition in the Gallbladder and Common Bile Duct of Patients with Anomalous Pancreaticobiliary Ductal Junction

Cited by 34 publications

References 7 publications

Papillary hyperplasia of the gallbladder in pancreaticobiliary maljunction represents a senescence-related lesion induced by lysolecithin

Papillary hyperplasia of the gallbladder in pancreaticobiliary maljunction represents a senescence-related lesion induced by lysolecithin

Bile from a patient with anomalous pancreaticobiliary ductal union promotes the proliferation of human cholangiocarcinoma cellsviaCOX-2 pathway

Carcinogenic potential of duodenal reflux juice from patients with long-standing postgastrectomy

Contact Info

Product

Resources

About