Benign Bile Duct Research Articles

A Promising Method for Repairing Low-Level Biliary Strictures After Cholecystectomy.

The purpose of this study is to introduce and evaluate a new technique of repairing bile ducts by the tubular gastric wall with a vascularized pedicle. Both the end-to-end bile duct repair and Roux-en-Y hepatoenterostomy have limitations in the treatment of benign bile duct strictures after cholecystectomy. There are no other good choices to manage these cases, especially the bile duct transection injuries or partly missing common bile duct or hepatic duct. Eleven patients with partly missing common bile ducts in the Chinese People's Liberation Army General Hospital between January 2007 and December 2012 were retrospectively analyzed. The study comprised 8 females and 3 males, whose age ranged from 29 to 56 years. All patients underwent successful bile duct repair. The time of operations ranged from 210 minutes to 240 minutes. The maximal blood loss was less than 220 ml. There was no perioperative mortality and no case of gastric fistula. Postoperative complications occurred in 3 patients, including wound infection, bile leakage, and erosive gastritis. All complications were cured by conservative treatment. The mean follow-up time was 42 months. One patient was classified as Terblanche's grade II and 10 patients were classified as Terblanche's grade I. The observations indicate that this technique is a feasible and effective choice to manage low level biliary stricture after cholecystectomy, especially suitable to repair bile duct transection injuries or partly missing common bile duct or hepatic duct.

Endoscopic Retrograde Cholangiopancreatography

Endoscopic retrograde cholangiopancreatography (ERCP) is a specialized endoscopic procedure to view the biliary and pancreatic ducts fluoroscopically. First introduced in the 1970s as a diagnostic tool, ERCP has since evolved primarily into a therapeutic modality and is today regarded as the premier tool for performing therapeutic interventions involving the biliary and pancreatic ductal systems. Relatively complex, ERCP requires advanced training. Although generally considered safe, it does carry a risk of significant complications, including pancreatitis; thus, the most important factor to mitigate complications is to ensure the presence of an appropriate indication for the procedure. This review addresses the indications (e.g., disorders of the major duodenal papilla, biliary diseases, and pancreatic diseases), contraindications, protocol, and complications of ERCP, as well as an overview of the tools available for ERCP procedures. Figures show ampullary adenomas, choledocholithiasis, Mirizzi syndrome, benign common bile duct stricture, primary sclerosing cholangitis, malignant biliary stricture, bile leak, type I and III choledochal cysts, chronic pancreatitis, pancreatic ductal disruption, classic fish-mouth appearance of the papilla in a patient with main duct intraductal papillary mucinous neoplasm, pancreas divisum, side-viewing duodenoscope used for ERCP, and selected tools of ERCP. Tables list the Rome III criteria, risk-stratifying patients for choledocholithiasis, diagnostic criteria for acute cholangitis, choledochal cyst classification, and the Cambridge classification system for chronic pancreatitis. This review contains 15 highly rendered figures, 5 tables, and 77 references.

No Distal Migration in Unfixed Versus Fixed Cell Structure Covered Self-Expanding Metal Stents for Treatment of Benign Biliary Disease.

Fully covered self-expandable metal stents (FCSEMS) are increasingly used for treatment of benign common bile duct (CBD) stricture or leakage, but dislodgement of FCSEMS is frequent. To compare dislocation rate and clinical outcome of a standard fixed cell structure FCSEMS (S-FCSEMS) to a novel FCSEMS with an unfixed cell structure (N-FCSEMS). We performed a retrospective analysis of all patients with FCSEMS insertion for benign biliary disease at our Hospital from 03/2008 to 03/2014. Both stent types N-FCSEMS and S-FCSEMS were applied as available unrelated to the indication. Twenty-nine patients (S-FCSEMS: 18, N-FCSEMS: 11) were included. Stent placement was technically successful in 28/29 (96.6%) patients; stent removal was successful in 26/27 (96.2%). Two patients with N-FCSEMS were excluded due to unsuccessful placement and withdrawal of consent for stent removal, respectively. Stent migration into the duodenum (distal migration) was observed in 9/18 (50%) in the S-FCSEMS group compared to 0/9 in the N-FCSEMS (p<0.005). FCSEMS migration into the CBD (proximal migration) was found in 2/18 (11%, S-FCSEMS) versus 2/9 (22%, N-FCSEMS, p=0.514). A foreshortening of the N-FCSEMS occurred in 3/9 patients (33%) compared to 0/18 S-FCSEMS (p=0.08). Clinical resolution of the treated CBD-disease was observed in 5/9 (56%, N-FCSEMS) versus 12/18 (67%, S-FCSEMS) at the time of stent removal (p=0.604) and in 0/9 and 10/18 (56%) cases during follow-up, respectively (p<0.005). An unfixed cell structure of FCSEMS seems to prevent distal migration, but proximal migration still occurs and foreshortening of the N-FCSEMS constrains clinical outcome.

Editorial introductions

Editorial introductions

BRAF V600E mutational status in bile duct adenomas and hamartomas.

Bile duct adenomas (BDA) and bile duct hamartomas (BDH) are benign bile duct lesions considered neoplastic or secondary to ductal plate malformation, respectively. We have reported previously a high prevalence of BRAF V600E mutations detected by allele-specific polymerase chain reaction assay in BDA, and suggested that BDA may be precursors to a subset of intrahepatic cholangiocarcinomas harbouring V600E mutations. The aim of the present study was to assess the existence of BRAF V600E mutations, using immunohistochemical methods, in additional BDA as well as in BDH. Fifteen BDA and 35 BDH were retrieved from the archives of the pathology departments of two French university hospitals. All cases were reviewed by two pathologists specialized in liver diseases. BRAF V600E mutational status was investigated by immunohistochemistry. Mutated BRAF mutant protein was detected in 53% of the BDA and in none of the cases of BDH. Our findings suggest that BDA and BDH are different processes, and that BDA represent true benign neoplasms. They also support the hypothesis that mutated BDA might precede the development of the subset of intrahepatic cholangiocarcinomas harbouring BRAF V600E mutations.

Long-term outcome of self expandable metal stents for biliary obstruction in chronic pancreatitis.

Insertion of a self-expandable metal stent is still controversial for treatment of benign common bile duct stenosis but can be a valuable alternative to surgical treatment. Aim of our study was to analyze the efficacy of covered and uncovered self-expandable metal stent in patients with chronic pancreatitis and common bile duct stenosis. Twenty patients with common bile duct stenosis due to alcoholic chronic pancreatitis were retrospective analyzed. All patients had advanced chronic pancreatitis, presenting with calcifications in pancreatic head. Uncovered self-expandable metal stent (uSEMS) were used in 11 patients (3 females, 8 males) while in 9 patients (3 females, 6 males) partially covered self-expandable metal stent (cSEMS) were inserted. All patients treated with self-expandable metal stent had contraindications for surgery. Overall mean follow up time was 155 weeks: 206 (52-412) weeks in uSEMS, and 93 (25-233) weeks in cSEMS, respectively. Stent patency was in mean 118 weeks: 159 (44-412) weeks in uSEMS and 67 (25-150) weeks in cSEMS (P=0.019). In the uSEMS group, reintervention was necessary in 5 patients (45%) due to stent obstruction, whereas in the cSEMS group 4 patients (44%) needed reintervention (2 obstructions, 2 migration). Stent migration is an early complication, compared to obstruction (P&lt;0.05), and in cSEMS obstruction occurred significantly earlier compared to uSEMS (P&lt;0.05). Patency of uSEMS was significantly longer compared to partially cSEMS. Available self-expandable metal stent, unfortunately, do not meet the demands on successful treatment of benign common bile duct stenosis.

Novel score for prediction of malignant bile duct obstruction based on biochemical and clinical markers.

Early differentiation of malignant from benign bile duct obstruction is of utmost importance. To identify biochemical and clinical predictors for malignancy in patients with bile duct obstruction, and establish a predictive model by combining pre-treatment patient characteristics. A web-based application was developed for easy assessment of malignant bile duct probability (www.pmal-score.org). One thousand hundred and thirty-five patients [median age 66 (52-75) years, 53% male] with bile duct obstruction of various aetiologies were retrospectively evaluated at our tertiary referral centre. Multivariate logistic regression analysis identified factors as independently significant for malignant bile duct obstruction. A predictive risk score was established using ROC analysis and applied to an external validation cohort of 101 patients. Three hundred and ninety-four patients had malignant bile duct obstruction proven by surgery, while in 741 patients benign obstruction was observed. Multivariate analysis identified various clinical factors to be predictive for malignancy. On the basis of eight predictors, a risk score for malignancy was developed [X=0.025*[age]+1.239*[1 if weight loss, otherwise 0]-0.235*[1 if pain, otherwise 0]+0.649*[1 if diabetes, otherwise 0]+0.896*[1 if jaundice, otherwise 0]+0.109*[bilirubin]+0.0007*[γ-GT]+0.0003*[AP]-4.374]: A significant correlation between the predicted malignancy and the actual malignancy was found by ROC (AUC: 0.862; 95% CI 0.838-0.886, P<0.0001). This predictive risk score estimates the risk of malignancy in patients with bile duct obstruction, and it seems to be very accurate. A better prediction enables both earlier diagnosis of malignant obstructive disease and improved management of patients with bile duct obstruction, which may result in reduced morbidity and mortality.

Endoscopic ultrasonography for differentiation of malignant and benign common bile duct strictures

Endoscopic ultrasonography for differentiation of malignant and benign common bile duct strictures

Identification of Novel Biomarker Candidates for the Immunohistochemical Diagnosis of Cholangiocellular Carcinoma

The aim of this study was the identification of novel biomarker candidates for the diagnosis of cholangiocellular carcinoma (CCC) and its immunohistochemical differentiation from benign liver and bile duct cells. CCC is a primary cancer that arises from the epithelial cells of bile ducts and is characterized by high mortality rates due to its late clinical presentation and limited treatment options. Tumorous tissue and adjacent non-tumorous liver tissue from eight CCC patients were analyzed by means of two-dimensional differential in-gel electrophoresis and mass-spectrometry-based label-free proteomics. After data analysis and statistical evaluation of the proteins found to be differentially regulated between the two experimental groups (fold change ≥ 1.5; p value ≤ 0.05), 14 candidate proteins were chosen for determination of the cell-type-specific expression profile via immunohistochemistry in a cohort of 14 patients. This confirmed the significant up-regulation of serpin H1, 14-3-3 protein sigma, and stress-induced phosphoprotein 1 in tumorous cholangiocytes relative to normal hepatocytes and non-tumorous cholangiocytes, whereas some proteins were detectable specifically in hepatocytes. Because stress-induced phosphoprotein 1 exhibited both sensitivity and specificity of 100%, an immunohistochemical verification examining tissue sections of 60 CCC patients was performed. This resulted in a specificity of 98% and a sensitivity of 64%. We therefore conclude that this protein should be considered as a potential diagnostic biomarker for CCC in an immunohistochemical application, possibly in combination with other candidates from this study in the form of a biomarker panel. This could improve the differential diagnosis of CCC and benign bile duct diseases, as well as metastatic malignancies in the liver.

688 Feasibility and Safety of Covered Self-Expandable Metal Stent (CSEMS) Placement Above the Hepatic Duct Confluence At ERCP in Benign Bile-Duct Disease

cSEMS appear to enhance therapeutic efficacy for benign distal bile-duct strictures and leaks. Concerns over the use of cSEMS above the hepatic duct confluence remain since clinical data are very limited.

Expression of CXC chemokine recetper 4 and its clinical significance in cholangiocarcinoma

Objective To investigate the relationship between CXC chemokine recetper 4 (CXCR4) expression to clinicopathological factors and prognosis in cholangiocarcinoma.Methods The expression of CXCR4 in 82 cases of cholangiocarcinoma,7 cases of benign bile duct neoplasms and 12 cases of non-tumor bile duct epithelium was detected by immunohistochemical staining,and that in 30 cases of cholangiocarcinoma by reverse transcriptase-polymerase chain reaction (RT-PCR).Results The positive expression rate of CXCR4 in 82 cases of cholangiocarcinoma,7 cases of benign bile duct neoplasms,and 12 cases of non-tumor bile duct epithelium was 75.6％,28.6％ and 0,respectively.The expression of CXCR4 in cholangiocarcinoma was significantly higher than that in benign bile duct neoplasms and non-tumor bile duct epithelium (P ＜0.01).The positive rate of CXCR4 was slightly higher in the stage Ⅱ-Ⅳ cases than that in the stage Ⅰ cases (22.4％ vs.7.3％,P ＞0.05).RT-PCR results revealed that the expression of CXCR4 mRNA in stage Ⅱ and Ⅲ cases was higher than that in stage Ⅰ cases (0.43 ± 0.07 vs.0.25 ± 0.08,P ＜ 0.05).The expression of CXCR4 mRNA in the cases with lymph node metastasis was significantly higher than that without lymph node metastasis (0.44 ± 0.07 vs.0.23 ± 0.03,P ＜ 0.05).Conclusion CXCR4 may play a positive role in carcinogenesis,invasion and metastasis of cholangiocarcinoma. Key words: Cholangiocarcinoma; CXC chemokine recetper 4 ; Prognosis

ERCP with double-channel endoscope for patients with Billroth-II gastroenterostomy

Objective To evaluate the therapeutic effect and safety of forward-viewing, double- channel endoscope in the process of ERCP in patients with bile duct diseases after Billroth- Ⅱ gastroenteros- tomy. Methods ERCP was applied to 46 patients with bile duct diseases using forward-viewing, double- channel endoscope. All patients had the history of BiUroth- Ⅱ gastroenterostomy. The success rate of selec- tive cannulation, complication rate and the outcome of all the patients were recorded. Results The proce- dure succeeded in 38 patients with a success rate of 82. 6%, and failed in 8. Of all the failing cases, the af- ferent loop couldn＇t be accessed in 6, failure in biliary cannulation in 2. Of 38 successful cases, bile duct stones were successfully removed in 31, metal stents placed for malignant bile duct obstruction in 4, and en- doscopic balloon dilation for benign common bile duct stricture in 3. All patients recovered without complica- tions of perforation, delayed bleeding or pancreatitis. Conclusion For patients with history of Billroth- Ⅱ gastroenterostomy, ERCP with forward-viewing, double-channel endoscope yields to a higher success rate and lower complication rate. Key words: Cholangiopancreatography, endoscopic retrograde; BiUroth- Ⅱ gastroenterostomy; Double-channel endoscope

Differentiation of infiltrative cholangiocarcinoma from benign common bile duct stricture using three-dimensional dynamic contrast-enhanced MRI with MRCP

To retrospectively evaluate the criteria for discriminating infiltrative cholangiocarcinoma from benign common bile duct (CBD) stricture using three-dimensional dynamic contrast-enhanced (3D-DCE) magnetic resonance imaging (MRI) combined with magnetic resonance cholangiopancreatography (MRCP) imaging and to determine the predictors for cholangiocarcinoma versus benign CBD stricture. 3D-DCE MRI and MRCP images in 28 patients with infiltrative cholangiocarcinoma and 23 patients with benign causes of CBD stricture were reviewed retrospectively. The final diagnosis was based on surgical or biopsy records. Two radiologists analysed the MRI images for asymmetry, including the wall thickness, length, and enhancement pattern of the narrowed CBD segment, and upstream CBD dilatation. MRI findings that could be used as predictors were identified by univariate analysis and multivariable stepwise logistic regression analysis. Malignant strictures were significantly thicker (4.4 ± 1.2 mm) and longer (16.7 ± 7.7 mm) than the benign strictures (p < 0.05), and upstream CBD dilatation was larger in the infiltrative cholangiocarcinoma cases (20.7 ± 5.7 mm) than in the benign cases (16.5 ± 5.2 mm; p = 0.018). During both the portal venous and equilibrium phases, hyperenhancement was more frequently observed in malignant cases than in benign cases (p < 0.001). The results of the multivariable stepwise logistic regression analysis showed that both hyperenhancement of the involved CBD during the equilibrium phase and the ductal thickness were significant predictors for malignant strictures. When two diagnostic predictive values were used in combination, almost all patients with malignant strictures (n = 26, 92.9%) and benign strictures (n = 21, 91.3%) were correctly identified; the overall accuracy was 92.2% with correct classifications in 47 of the 51 patients. Infiltrative cholangiocarcinoma and benign CBD strictures could be effectively differentiated using DCE-MRI and MRCP based on hyperenhancement during the equilibrium phase and bile wall thickness of the involved segment.

Bile Duct Adenoma with Oncocytic Features

Bile duct adenomas are benign bile duct proliferations usually encountered as an incidental finding. Oncocytic bile duct neoplasms are rare and the majority are malignant. A 61-year-old male with a diagnosis of colorectal adenocarcinoma was undergoing surgery when a small white nodule was discovered on the surface of the right lobe of his liver. This lesion was composed of cytologically bland cells arranged in tightly packed glands. These cells were immunopositive for cytokeratin 7, negative for Hep Par 1, contained mucin, and had a Ki67 proliferation index of 8%. The morphology, immunophenotype, presence of mucin, and normal appearing bile ducts, as well as the increased Ki67 proliferation rate, were consistent with a bile duct adenoma with oxyphilic (oncocytic) change. Oncocytic tumors in the liver are rare; the first described in 1992. Only two bile duct adenomas with oncocytic change have been reported and neither of them had reported mucin production or the presence of normal appearing bile ducts within the lesion.

Choledochoduodenostomy as the Biliary–Enteric Bypass of Choice for Benign and Malignant Distal Common Bile Duct Strictures

Choledochoduodenostomy (including hepaticoduodenostomy) for common bile duct (CBD) strictures has been underused because of concerns regarding postoperative duodenal fistula and cholangitis attending the so-called "sump syndrome." An institutional retrospective review of 55 consecutive choledochoduodenostomy procedures for CBD strictures from 1995 to 2011 was performed to examine its suitability as the biliary-enteric bypass procedure of choice. There were 30 male (55%) and 25 female (45%) patients with a mean age of 49 years (range, 13 to 73 years). Thirty-seven (67%) patients had benign CBD strictures and 18 (33%) had unresectable periampullary adenocarcinomas. Forty-nine (89%) underwent choledochoduodenostomy and six (11%) underwent hepaticoduodenostomy. There were no 30-day postoperative deaths, anastomotic leaks, or intra-abdominal abscesses. Five patients (9%) sustained Clavien Grade III or IV complications. Over a mean long-term follow-up of 29 months (range, 1 to 162 months), there was one anastomotic stricture successfully managed by endoscopic dilation and temporary stenting. Liver function tests in all other patients returned to and remained within normal limits. We conclude that choledochoduodenostomy is the preferred biliary-enteric bypass for both benign and malignant distal CBD strictures because of its ease, safety, and durability. Persistent fears of duodenal fistula and the "sump syndrome" are not warranted by the empiric data and should be abandoned.

Differential Expression of Fascin, E-cadherin and Vimentin: Proteins Associated With Survival of Cholangiocarcinoma Patients

IntroductionThis study investigated the differential expression of fascin, E-cadherin and vimentin in human carcinogenesis. MethodsThis study detected their expressions in 142 cholangiocarcinoma and 20 benign bile duct tissue specimens using immunohistochemistry. Clinicopathologic characteristics and survival data were also collected and analyzed for their association with expression of these 3 proteins. ResultsThe data showed that both fascin and vimentin proteins were significantly overexpressed in cholangiocarcinoma, whereas E-cadherin expression was reduced in cholangiocarcinoma compared with normal tissues. Fascin protein expression was associated with tumor dedifferentiation, venous invasion and lymph node or distant metastasis. Similarly, vimentin expression was associated with tumor dedifferentiation and venous invasion, as well as hepatitis virus infection. In contrast, loss of E-cadherin expression was associated with tumor dedifferentiation (P<0.05). Because the functions of these 3 proteins were closely related, the data showed that fascin and E-cadherin protein expression was reversely associated. However, fascin and vimentin protein expression was positively associated with cholangiocarcinoma. Cox multiple regression analysis showed that distant tumor metastasis, tumor differentiation and overexpression of fascin and vimentin proteins were all independent risk factors for prognosis (P<0.05). ConclusionThe data from the current study demonstrated that overexpression of fascin and vimentin proteins could be further evaluated as biomarkers for the prediction of cholangiocarcinoma patient survival.

Expression of peptidyl-prolyl isomerase PIN1 and its role in the pathogenesis of extrahepatic cholangiocarcinoma

The phosphorylation of proteins on serine/threonine residues that immediately precede proline (pSer/Thr-Pro) is a key signaling mechanism by which cell cycle regulation and cell differentiation and proliferation occur. The peptidyl-prolyl isomerase PIN1-catalyzed conformational changes of the pSer/Thr-Pro motifs may have profound effects on the function of numerous oncogenic and cell signaling pathways. To date, no studies have examined the expression of PIN1 and its potential role in the pathogenesis of extrahepatic cholangiocarcinoma (ECC). Therefore, the present study performed an immunohistochemistry analysis of the expression of PIN1 in 67 cases of ECC and evaluated its association with clinicopathological factors. In addition, the role of PIN1 was examined using synthetic small interfering RNA (siRNA) to silence PIN1 gene expression in human CC RBE cells. Positive PIN1 expression was observed in 35 of the 67 (52.2%) ECC cases and was predominantly localized to the nucleus of the tumor cells. The immunoreactive score for PIN1 was significantly higher in the tumor cells (4.07±0.4) compared with the adjacent benign bile duct cells (1.19±0.4) (P<0.001). PIN1 expression was significantly correlated with tumor cell proliferation (Ki-67 labeling index; P=0.024). Silencing PIN1 expression using siRNA significantly decreased the proliferation, migration and invasion of the tumor cells. In conclusion, the results indicated that the expression of PIN1 may play a key role in the development and progression of ECC.

Retrograde biliary stenting in patients with pancreatobiliary diseases

Aim. To evaluate the results of retrograde biliary stenting in patients with pancreatobiliary diseases. Methods. In 2008-2012, 85 retrograde biliary stenting procedures were performed in 65 patients (28 men and 37 women) with pancreatobiliary diseases aged 33 to 86 years. Obstructive jaundice was diagnosed in 44 of 65 patients (in 67% of cases), ascending cholangitis - in 14 (21%) patients. Endoscopic biliary stenting was performed in 47 patients with benign pancreatobiliary diseases (chronic and post-surgical pancreatitis, benign common bile duct stricture, Mirizzi syndrome, intradiverticular papilla, common bile duct bile stones) and in 18 patients with malignancies (cancers of pancreas head, bile ducts and papillary cancer). Plastic biliary stents with a (diameter 2.5 to 3.3 mm) were used for stenting. Results. Endoscopic biliary stenting allows to resolve the clinical manifestations of оbstructive jaundice and cholangitis, to eliminate pain, to prevent the development of pancreatitis, to prepare patients for surgery. Serious complications of biliary stenting (stent migration in common bile duct, acute cholangitis) were observed in 5 of 85 procedures (5.9% of cases), and all were resolved after repeated endoscopic intervention. Conclusion. Endoscopic retrograde biliary stenting is a safe and effective treatment option for patients with both benign and malignant pancreatobiliary diseases, it is characterized by low rate of specific complications (5.8%) and had reduced the risk of acute pancreatitis in patients with papillostenosis and stricture of the common bile duct terminal part down to 3%.

Appearances of von Meyenburg Complex on Cross Sectional Imaging

The von Meyenburg complex (VMC) is an uncommon congenital malformation and is characterized by benign bile duct hamartomas. These are usually discovered incidentally and may represent a diagnostic dilemma when liver metastases are suspected. MRI of VMC shows distinct imaging characteristics, but reporting of lesional contrast enhancement has been inconsistent, whilst microbubble contrast enhanced ultrasound provides ‘real-time’ evaluation of soft tissue vascularity. Given the diagnostic uncertainty over imaging in VMC, biopsy is often recommended as the definitive diagnosis. We report a biopsy proven case of VMC on a background of primary colonic malignancy investigated with ultrasound, contrast enhanced ultrasound, computed tomography CT, and magnetic resonance imaging MRI, and review the key imaging features.

The progress of biodegradable biliary stents

Biodegradable stents have achieved encouraging outcomes in the treatment of benign bile duct stenosis with good biocompatibility,unique biodegradation,and adept physical and mechanical performance.They have a higher biocompatibility than plastic and metal stents and do not require a second surgery for removal.This prevents adverse reactions like restenosis and the tendency to punch and bleed.These biodegradable stents provide a new method of treatment for biliary tract disease,and this review will focus on the animal experiments,clinical application,and future prospects of these stents. Key words: Bile duct diseases; Stents; Biocompatible materials