Removal of intrahepatic bile duct stone could reduce the risk of cholangiocarcinoma: A single-center retrospective study in South Korea

BACKGROUND Intrahepatic duct(IHD)stones are among the most important risk factors for cholangiocarcinoma(CCC).Approximately 10%of patients with IHD stones develop CCC;however,there are limited studies regarding the effect of IHD stone removal on CCC development.AIM To investigate the association between IHD stone removal and CCC development.METHODS We retrospectively analyzed 397 patients with IHD stones at a tertiary referral center between January 2011 and December 2020.RESULTS CCC occurred in 36 of the 397 enrolled patients.In univariate analysis,chronic hepatitis B infection(11.1%vs 3.0%,P=0.03),carbohydrate antigen 19-9(CA19-9,176.00 vs 11.96 II/mL,P=0.010),stone located in left or both lobes(86.1%vs 70.1%,P=0.042),focal atrophy(52.8%vs 26.9%,P=0.001),duct stricture(47.2%vs 24.9%,P=0.004),and removal status of IHD stone(33.3%vs 63.2%,P<0.001)were significantly different between IHD stone patients with and without CCC.In the multivariate analysis,CA19-9>upper normal limit,carcinoembryonic antigen>upper normal limit,stones located in the left or both lobes,focal atrophy,and complete removal of IHD stones without recurrence were independent factors influencing CCC development.However,the type of removal method was not associated with CCC risk.CONCLUSION Complete removal of IHD stones without recurrence could reduce CCC risk.

Modified rendezvous intrahepatic bile duct cannulation technique to pass a PTBD catheter in ERCP

The rendezvous procedure combines an endoscopic technique with percutaneous transhepatic biliary drainage(PTBD).When a selective common bile duct cannulation fails,PTBD allows successful drainage and retrograde access for subsequent rendezvous techniques.Traditionally,rendezvous procedures such as the PTBDassisted over-the-wire cannulation method,or the parallel cannulation technique,may be available when a bile duct cannot be selectively cannulated.When selective intrahepatic bile duct(IHD) cannulation fails,this modified rendezvous technique may be a feasible alternative.We report the case of a modified rendezvous technique,in which the guidewire was retrogradely passed into the IHD through the C2 catheter after end-to-end contact between the tips of the sphincterotome and the C2 catheter at the ampulla's orifice,in a 39-year-old man who had been diagnosed with gallbladder carcinoma with a metastatic right IHD obstruction.Clinically this procedure may be a feasible and timesaving technique.

The abnormal expression of E-cadherin in intrahepatic bile duct epithelia cells in biliary atresia and its relationship with apoptosis

To explore the relationship between the expression of E-cadherin and the apoptosis in intrahepatic bile duct epithelial cells in biliary atresia (BA).Methods The E-cadherin expression was demonstrated by immunohistochemical staining for the liver specimens from 38 children with BA and 16 normal children.The apoptotic intrahepatic bile duct epithelial cells in these specimens were visualized by TdT-mediated dUTP-digoxigenin nick end labeling (TUNEL) assay,and the apoptotic index (AI) was calculated from the percentage of apoptotic cells in total cells.Results The intensity of E-cadherin expression in bile duct epithelial cells in BA group was lower than that in the normal control group (0.33±0.12 vs 0.62±0.20,P<0.01).On the other hand,the AI in BA group was significant higher than that in control group (51.74±19.93 vs 12.34±19.32,P<0.01).An inverse correlation was detected between the intensity of E-cadherin and the AI in the liver from children with BA.Conclusion The abnormal decrease of E-cadherin may lead to an increase of the apoptosis of intrahepatic bile epithelial cells in BA,resulting in developmental disorder of intrahepatic bile duct and ductal plate malformation in the liver.12 refs,4 figs,1 tab.

Apoptosis and proliferation of intrahepatic bil educt after ischemia-reperfusion injury

BACKGROUND: In orthotopic liver transplantation, ische-mic-reperfusion is one of the most important factors thatcause the incidence of biliary complicance. The aim of thisstudy was to investigate the effects of ischemia reperfusionon epithelial cells apoptosis and proliferation of intrahepaticbile duct (IBD) (>20 μm).METHODS: 30-minute warm ischemia was applied to ratlivers respectively, and experiment was performed on days2,7, 14, 28 after reperfusion. Apoptosis was determined insitu by morphology and TUNEL, and cholangiocyte proli-feration was evaluated in situ by morphometry of liver sec-tions stained for cytokeratin-19 ( CK-19) and by prolifera-ting cellular nuclear antigen staining in liver sections.RESULTS: Two days after ischemia reperfusion, apoptosisof cells was observed in large intrahepatic bile ducts (>20μm) (5.6%±1.2%) , but the number of large intrahepaticbile ducts reduced (0.32 ±0.06). Seven days after ischemiareperfusion, the apoptosis index of cholangiocytes de-creased to 1.2%±0.3%, and the number of intrahepatic bileducts began to proliferate and returned to nearly normal onday 28.CONCLUSION: Ischemia reperfusion causes a decrease inthe number of intrahepatic bile ducts (>20 μm) as a resultof a higher rate of apoptosis and absence of initial prolifera-tion.

Clinical characteristics of intrahepatic biliary papilloma:A case report

BACKGROUND Intrahepatic bile duct papilloma(IPNB)is a rare benign tumour from the bile duct epithelium and has a high malignant transformation rate.Early radical resection can obviously improve the prognosis of patients,but it is difficult to be sure of the diagnosis of IPNB before operating.CASE SUMMARY This study included 28 patients with intraductal papilloma admitted to the First Hospital of Jilin University from January 2010 to November 2020 and recorded their clinical manifestations,imaging features,complications and prognosis.There were 12 males and 16 females with an average age of 61.36±8.03 years.Most patients had symptoms of biliary obstruction.Biliary dilatation and cystic mass could be seen on imaging.After surgery,IPNB was diagnosed by pathology.CONCLUSION IPNB is a rare benign tumour in the bile duct.Early diagnosis and timely R0 resection can improve the prognosis of IPNB.

Postoperative jaundice related to UGT1A1 and ABCB11 gene mutations:A case report and literature review

BACKGROUND Patients with obstructive jaundice caused by intrahepatic bile duct stones can be effectively managed by surgery.However,some patients may develop postope-rative complications,liver failure,and other life-threatening situations.Here,we report a patient with mutations in the uridine 5’-diphospho-glucuronosyltrans-ferase 1A1(UGT1A1)and bile salt export pump(adenosine triphosphate-binding cassette subfamily B member 11,ABCB11)genes who presented multiple intrahe-patic bile duct stones and cholestasis,and the jaundice of the patient increased after partial hepatectomy.CASE SUMMARY A 52-year-old male patient admitted to the hospital on October 23,2021,with a progressive exacerbation of jaundice,was found to have multiple intrahepatic bile duct stones with the diagnoses of obstructive jaundice and acute cholecystitis.Subsequently,the patient underwent left hepatectomy with biliary exploration,stone extraction,T-tube drainage,and cholecystectomy without developing any intraoperative complications.The patient had a dark urine color with worsening jaundice postoperatively and did not respond well to plasma exchange and other symptomatic and supportive treatments.Since the progressive increase in postoperative bilirubin could not be clinically explained with any potential reason,including,if not at all,viral infection,cholangitis,autoimmune liver disease,and other causes,the patient underwent whole-exon screening for any genetic diseases,which surprisingly identified UGT1A1 and ABCB11 gene mutations related to glucuronidation of indirect bilirubin as well as bile acid transport in hepatocytes,respectively.Thus,we hypothesized that postoperative refractory cholestasis might result from UGT1A1 and ABCB11 gene mutations and further recommended liver transplantation to the patient,who eventually declined it and died from liver failure six months later.CONCLUSION Surgery may aggravate cholestasis in patients with multiple intrahepatic bile duct stones and cholestasis associated with UGT1A1 and ABCB11 gene mutations.A liver transplant may be the best option if active medical treatment fails.

Correlation between Expression Differences of Epithelial-Mesenchymal Transition (EMT) in Cholangiocarcinoma Tissue

Background: By studying the expression of epithelial-mesenchymal transition regulators in cholangiocarcinoma and intrahepatic duct stones, the correlation between the expression of epithelial-mesenchymal transition regulators and cholangiocarcinoma was revealed. Objective: The objective is to investigate the correlation between the expression of epithelial-mesenchymal transition (EC) regulatory factors and cholangiocarcinoma in patients with intrahepatic duct stones and cholangiocarcinoma, to investigate the relationship between clinicopathological features and prognosis, and to observe the expression of molecular markers of epithelial-mesenchymal transition (EMT) in intrahepatic duct stones and bile duct carcinoma. Methods: Twenty cases of primary cholangiocarcinoma, 20 cases of intrahepatic cholangiolithiasis complicated with cholangiocarcinoma, and 20 cases of intrahepatic cholangiolithiasis specimens were collected from the Fourth People’s Hospital and the friendly medical unit of Haikou. Immunohistochemistry was used to detect the expression differences of EMT-related molecular markers Twisit1, Twisit2, E-cadherin, N-cadherin, and Vimentin in paraffin sections of normal intrahepatic bile duct tissues and patients with intrahepatic duct stones and cholangiocarcinoma. Results: Immunohistochemical staining revealed epithelial-mesenchymal transition (EMT) in intrahepatic cholangiocarcinoma tissue, intrahepatic cholangiolithiasis with cholangiocarcinoma, intrahepatic cholangiolithiasis with normal intrahepatic cholangiolithiasis, such as Sit1, Twisit2, E-cadherin, N-cadherin, and Vimentin proteins were different. The expression of E-cadherin was decreased in cholangiocarcinoma tissue and intrahepatic cholangiolithiocarcinoma combined with cholangiocarcinoma (P < 0.05), while the expression of N-cadherin and Vimentin was up-regulated (P < 0.05). The expression of Twisit1 and Twisit2 had no difference (P > 0.05). There was no difference in the expression of intrahepatic bile duct stones and EMT (P > 0.05). Conclusion: The expression of E-cadherin, the molecular marker of EMT, was down-regulated, while the expression of N-cadherin and Vimentin was up-regulated. Age, gender, depth of tumor invasion, degree of tumor differentiation and lymph node metastasis were correlated with the expression of EMT in intrahepatic cholangiocarcinoma.