Benign Bile Duct Diseases Research Articles

Follicular cholangitis mimicking a common bile duct cancer: a case report

BackgroundFollicular cholangitis (FC) is a benign bile duct disease that was first reported 2003. Pathologically, it is characterized by lymphoplasmacytic infiltration with multiple lymphoid follicle formations under the mucosal layer of the biliary tract. However, as this disease is extremely rare, little is known about its etiology and pathogenesis.Case presentationA 77-year-old woman was diagnosed with middle bile duct stenosis and potential increases in alkaline phosphatase (ALP) and γ-glutamyl transpeptidase levels (γ-GTP). Carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) and IgG4 levels were all within the normal limits. Contrast-enhanced computed tomography (CE-CT) and magnetic resonance imaging (MRI) revealed bile duct dilation from intrahepatic to upper common bile duct and an irregular mass lesion in distal bile duct. Additionally, multiple overlapping leaf-like folds were detected. 18F-fluorodeoxyglucose positron emission tomography–computed tomography (18F-FDG-PET/CT) did not demonstrate fluorodeoxyglucose uptake. Subtotal stomach-preserving pancreaticoduodenectomy with regional lymph node dissection was performed because common bile duct cancer could not be ruled out. The resected specimen showed diffuse homogeneous middle bile duct wall thickening. Microscopically, the lesion exhibited thick fibrosis with several invaded lymphoplasmacytic cells, and lymphoid follicle formations were detected under the mucosal layer. Immunohistochemical staining (IHC) revealed positive for CD3, CD4, CD20 and CD79a, and these findings led to a final diagnosis of FC. The patient has not experienced recurrence to date (42 months postoperatively).ConclusionsCurrently, accurate preoperative diagnosis of FC is difficult. More cases must be accumulated to generate additional knowledge on its precise diagnosis and proper treatment.

Laparoscopic Choledochoduodenostomy in Bile Duct Stone Diseases

Common bile duct (CBD) stones are present in 5–15% of patients with gallstones. Some of these patients are candidates for a definitive biliary drainage procedure for prevention of stone recurrence. The aim of our study was to ascertain the outcome of laparoscopic choledochoduodenostomy in choledocholithiasis. After obtaining ethical clearance from the institutional ethical committee, the present prospective and observational study was conducted on 32 patients over a period from September 2017 to September 2020 in the tertiary care hospital. In our study, the total number of patients was 32, of whom 26 (81%) were females. The mean and range of age were 54.44 SD 10.827 and 24–70 years, respectively. The most common presenting feature was jaundice (53.125%). The mean CBD diameter was 24.59 SD 2.564 mm with multiple stones in CBD in 90.625% of our patients. The mean duration of surgery and intraoperative blood loss was 147.94 SD 9.732 and 76.25 SD 12.636 ml, respectively. The mean hospital stay was 6.34 SD 0.827 days with 90.6% of the patients returning to work in the 3rd week. In our study, there was no conversion to open and a single patient developed postoperative ileus which was managed conservatively. There was complete resolution of symptoms on follow-up. Laparoscopic choledochoduodenostomy is safe for benign bile duct diseases. It is physiological, with minimal intraoperative blood loss, less operative time, and fewer postoperative complications and is safe with faster recovery.

The diagnostic and prognostic value of UBE2T in intrahepatic cholangiocarcinoma.

BackgroundUbiquitin-conjugating enzyme E2T (UBE2T) is overexpressed in several types of malignancies. However, little is known about its diagnostic significance in intrahepatic cholangiocarcinoma (ICC) and other bile duct diseases or its prognostic value in ICC.MethodsThe expression levels of UBE2T in the intrahepatic bile duct (IHBD, N = 13), biliary intraepithelial neoplasia (BilIN; BilIN-1/2, N = 23; BilIN-3, N = 11), and ICC (N = 401) were examined by immunohistochemistry. The differential diagnostic and prognostic values were also assessed.ResultsThe number of UBE2T-positive cells was significantly higher in ICC tissues than in nonmalignant tissues, including the IHBD, BilIN-1/2, and BilIN-3 tissues. Kaplan–Meier analysis showed that overexpression of UBE2T was correlated with a shorter time to recurrence (TTR) and overall survival (OS). The 5-year TTR rates in the high UBE2T and low UBE2T groups were 100% and 86.2%, respectively. The corresponding OS rates were 1.9% and 22.2%, respectively. High expression of UBE2T was an independent risk factor for both TTR (hazard ratio: 1.345; 95% confidence interval: 1.047,1.728) and OS (hazard ratio: 1.420; 95% confidence interval: 1.098,1.837).ConclusionsUBE2T can assist in differentiating benign bile duct diseases from ICC, and high expression of UBE2T suggests a poor prognosis for ICC.

An extremely increased CA19-9 level due to common bile duct stone: a case report

Serum carbohydrate antigen 19-9 (CA19-9), a common tumor marker, is frequently increased in bile duct malignancy. We reported a case with an extremely increased CA19-9 level due to benign common bile duct stones and gallstones. A 63-year-old male presented with intermittent right upper quadrant abdominal pain for 1 year. Tumor markers showed that CA19-9 level was more than 1,000.0 U/mL (normal range: 0–37 U/mL), CA-50 level was 466.34 IU/mL (normal range: 0–25 IU/mL), and CA24-2 level was more than 200 IU/mL (normal range: 0–20 IU/mL). Abdominal CT scan and magnetic resonance cholangiopancreatography (MRCP) demonstrated multiple stones located in the lower segment of common bile duct, lower bile duct obstruction, and gallbladder stones. Pancreatic cancer and cholangiocarcinoma were excluded. On the third day after endoscopic retrograde cholangiopancreatography (ERCP), CA19-9 level dropped to 78.62 U/mL. In conclusion, an extremely increased CA19-9 level might be observed in some patients with benign bile duct diseases.

The diagnostic and prognostic value of MRP8/MRP14 in intrahepatic cholangiocarcinoma.

Myeloid-related protein 8 (MRP8) and 14 (MRP14) are abundantly expressed in several kinds of benign and malignant tumors. However, little is known about their clinicopathological significance in intrahepatic cholangiocarcinoma (ICC), biliary intraepithelial neoplasia (BilIN), intraductal papillary neoplasm of bile duct (IPNB), or inflammatory hepatic biliary ducts epithelium (IHBD). This study aimed to investigate the diagnostic and prognostic values of MRP8 and MRP14 as new biomarkers for ICC. We examined MRP8 and MRP14 expression levels by immunohistochemistry in IHBD (n = 15), BilIN (BilIN1 = 24, BilIN2 = 9, BilIN3 = 5), IPNB (n = 18) and ICC (n = 416). The differential diagnostic and prognosis values were also evaluated. The results showed that the ratio of tumor-infiltrating MRP8 and MRP14 positive immune cells, relative to biliary epithelial cells, was significantly increased in ICC tissues compared with nonmalignant tissues, including IHBD, BilIN1, BilIN2, BilIN3, and IPNB (P value < 0.05). In addition, over-expression levels of MRP8 and MRP14 were correlated with overall survival (OS) and time to recurrence (TTR) by univariate analysis; MRP8/MRP14 combination was an independent prognostic factor for OS and TTR. MRP8 and MRP14 expression might help to identify the benign bile duct diseases from ICC, as high expression of MRP8 and MRP14 suggests a poor prognosis after surgical resection.

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.

Glycoproteomics-based cancer marker discovery adopting dual enrichment with Wisteria floribunda agglutinin for high specific glyco-diagnosis of cholangiocarcinoma

Cholangiocarcinoma (CC) is a lethal malignancy because it exhibits asymptomatic growth infiltrating the surrounding structures and therefore is usually detected at an advanced stage. The mainstay of treatment for CC is complete resection with negative surgical margins. Therefore, its diagnosis at a relatively early stage is demanded for performing relevant surgical resection. Since the definitive CC diagnosis depends on invasive methods such as biliary cytology and biopsy, a noninvasive assay with high diagnostic accuracy is keenly required. We therefore developed a CC marker with high specificity by the Wisteria floribunda agglutinin (WFA)-assisted glycoproteomics approach. WFA-positive glycoproteins were enriched by the direct dissection of the WFA-stained CC tissue region and following WFA-agarose column chromatography. Subsequent analysis by mass spectrometry identified 71 proteins as candidate markers. Screening of these candidates by gene expression profiling and immunohistochemistry resulted in the selection of L1 cell adhesion molecule (L1CAM) as the most specific CC marker. We confirmed the importance of WFA-positivity for L1CAM using both bile and serum of CC and benign bile duct disease patients. Specifically, WFA-positive L1CAM was enriched from serum by the WFA-assisted affinity capturing, with which CC was efficiently distinguished from benign. In the primary verification study using bile from CC patients (n=29) and that of benign bile duct disease (n=29), WFA-positive L1CAM distinguished CC with high specificity (sensitivity=0.66, specificity=0.93, overall accuracy=0.79, area under the receiver operating curve [AUC]=0.82). The combined use of the WFA-positive L1CAM assay with the high sensitive assay detecting WFA-positive sialylated mucin 1 sufficiently improved the diagnostic accuracy of CC (overall accuracy=0.84, AUC=0.93). This combination will possibly be a precise procedure for CC diagnosis compared with conventional diagnostic techniques. In this study, we constructed the system for verification of the candidate molecules that exhibit disease specific glyco-alterations and discovered a useful CC marker by the glycoproteomics-assisted strategy for biomarker discovery. Based on the strategy, we previously found that WFA is the best probe to detect CC-specific glycosylation and WFA-positive sialyl MUC1 as a possible biomarker candidate. While the diagnostic specificity of WFA-positive sialyl MUC1 was not superb, we proposed a new biomarker candidate WFA-positive L1CAM with high specificity in bile and serum to complement the previous one. We proved that the novel combination assay of WFA-L1CAM and WFA-sialyl MUC1 selected based on our strategy has the possibility to become a reliable serological test. This study represents application of our strategy, which can be extrapolated to discovery of marker candidates for other diseases.

Detection of serum MMP-7 and MMP-9 in cholangiocarcinoma patients: evaluation of diagnostic accuracy

BackgroundCholangiocarcinoma is an aggressive tumor with a tendency for local invasion and distant metastases. Timely diagnosis is very important because surgical resection (R0) remains the only hope for a cure. However, at present, there is no available tumor marker that can differentiate cholangiocarcinoma from benign bile duct disease. Previous studies have demonstrated that matrix metalloproteinase (MMP)-7 and MMP-9 are frequently expressed in cholangiocarcinoma specimens.MethodsThis study was designed to determine whether the serum levels of MMP-7 and MMP-9 can discriminate cholangiocarcinoma patients from benign biliary tract disease patients in comparison to carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). We measured the level of CEA, CA19-9, MMP-7 and MMP-9 in the serum of 44 cholangiocarcinoma and 36 benign biliary tract diseases patients.ResultsAmong the serum levels of CEA, CA19-9, MMP-7 and MMP-9, only the serum MMP-7 level was significantly higher in the patients with cholangiocarcinoma (8.9 ± 3.43 ng/ml) compared to benign biliary tract disease patients (5.9 ± 3.03 ng/ml) (p < 0.001). An receiver operating characteristic (ROC) curve analysis revealed that the detection of the serum MMP-7 level is reasonably accurate in differentiating cholangiocarcinoma from benign biliary tract disease patients (area under curve = 0.73; 95% CI = 0.614–0.848). While the areas under the curve of the ROC curves for CEA, CA19-9 and MMP-9 were 0.63 (95% CI = 0.501–0.760), 0.63 (95% CI = 0.491–0.761) and 0.59 (95% CI = 0.455–0.722), respectively.ConclusionSerum MMP-7 appears to be a valuable diagnostic marker in the discrimination of cholangiocarcinoma from benign biliary tract disease. Further prospective studies for serum MMP-7 measurement should be carried out to further investigate the potential of this molecule as a biomarker of cholangiocarcinoma.

Expression of RECK gene and MMP-9 in hilar cholangiocarcinoma and its clinical significance

In order to study the expression of transformation suppressor gene RECK and MMP-9 in hilar cholangiocarcinomas and its clinical significance, and explore the roles of RECK gene in metastasis and invasion of hilar cholangiocarcinoma, the expression levels of RECK, and MMP-9 mRNA were detected by using reverse transcription-polymerase reaction in 42 paraffin-embedded samples of hilar cholangiocarcinomas and 10 samples of benign bile duct diseases. The results showed that in hilar cholangiocarcinoma tissues, the expression of RECK gene was 0.235 +/- 0.062, significantly lower than in normal bile duct tissues (0.533 +/- 0.024, P < 0.05). In hilar cholangiocarcinoma tissues, the expression of MMP-9 (0.528 +/- 0.039) was significantly higher than in the normal tissues (0.311 +/- 0.032, P < 0.05). The expression of RECK gene was closely related to the intrahepatic and surrounding organs invasion (P < 0.05). It was concluded that RECK gene could inhibit the expression of MMP-9 in hilar cholangiocarcinomas and closely correlated with the biological behaviors. The abnormal expression of RECK gene might be one of the molecular mechanisms of hilar cholangiocarcinoma metastasis.

Radiologic spectrum of cholangiocarcinoma: emphasis on unusual manifestations and differential diagnoses.

Most cholangiocarcinomas are ductal adenocarcinomas that arise from both intra- and extrahepatic bile duct epithelium, and their typical growth pattern can be classified as exophytic, infiltrative, polypoid, or a combination of these. Those of unusual histologic type (eg, mucin-hypersecreting cholangiocarcinoma, squamous adenocarcinoma, biliary cystadenocarcinoma, and mucinous carcinoma) show a growth pattern different from that of the typical ones (ie, ductal). Cholangiocarcinomas frequently develop in patients with any of a variety of preexisting bile duct diseases, some of which are considered precursors of cholangiocarcinoma (eg, biliary lithiasis, clonorchiasis, recurrent pyogenic cholangitis, and primary sclerosing cholangitis). Some bulky hepatic tumors of either primary or secondary origin mimic exophytic peripheral cholangiocarcinoma. Some variants of hepatocellular carcinoma, such as sclerosing, fibrolamellar, and cholangiohepatocellular carcinoma, resemble exophytic peripheral cholangiocarcinoma, while that with intraductal growth resembles polypoid cholangiocarcinoma. Among benign bile duct diseases, tumorous conditions (eg, benign biliary tumors) may mimic polypoid cholangiocarcinoma, whereas benign stricture of various causes (eg, cholangitides, traumatic and postsurgical sequelae, chronic pancreatitis, papillary stenosis) usually mimics infiltrative cholangiocarcinoma.

Characterization of biliary strictures using intraductal ultrasonography: comparison with percutaneous cholangioscopic biopsy

Background: We determined the accuracy of intraductal ultrasonography (IDUS) in distinguishing between bile duct cancer and benign bile duct disease. Methods: Patients (n = 42) who required bile duct biopsy using percutaneous transhepatic cholangioscopy (PTCS) to evaluate bile duct strictures or filling defects were studied. A thin-caliber ultrasonic probe (2.0 mm diameter and 20 MHz frequency) was inserted into the bile duct, and its images were prospectively reviewed before PTCS. Results: Disruption of the bile duct wall structure, seen on IDUS, was associated with malignancy in 25 of 26 patients. When IDUS demonstrated a lesion with normal bile duct structure, six of nine patients were found to have no malignancy. IDUS demonstrated no intraductal lesion in seven patients, and bile duct biopsy also did not indicate cancer in any of these patients. The accuracy, sensitivity, and specificity of IDUS for diagnosing bile duct cancer were 76%, 89%, and 50%, respectively. When used in tandem with IDUS, the sensitivity of bile cytology (64%) and PTCS (93%) improved to 96% and 100%, respectively. Conclusions: The accuracy of IDUS for diagnosing bile duct cancer was less than that of PTCS (95%). However, the sensitivity for bile cytology, or bile duct biopsy improved when performed in combination with IDUS. (Gastrointest Endosc 1998;47:341-9.)

THE MANAGEMENT OF BENIGN BILE DUCT STRICTURES

Benign bile duct strictures have varicolored origin and high morbidity. In an effort to evaluate the spectrum of these strictures, a retrospective analysis was carried out on 105 consecutive patients with benign duct stricture treated at the department between 1985 and 1994. These 105 lesions represented 6.0% of all benign bile duct diseases. Bile duct damage was most frequently found in the middle-lower bile duct area (74.5%). The stricutres were caused by non-operative factorsin 81.5% and operative factors in 18.5%. Among non-operative factors Vater's stricture and congenital disease were common. Operative factors included intraoperative bile duct injury in 8 cases and postoperative cicatrization in 10 cases. After biliary reconstruction, stricture occured at the anastomosed site in 4 cases. As to postoperative strictures, it occurred in 4 (1.66%) out of 236 cases undergoing choledochodrainage by inserting a T tube; in 2 (0.16%) out of 1256 cases undergoing cholecystectomy; and in 4 olut of 374 cases undergoing biliary reconstruction. The postoperative strictures had an average disease-free period of 2.12 years after the operation for the primary disease. As to treatments of the stricture, standard operation was done for 98 cases and interventional radiologic technique for 6 cases. The standard operation was successful in 91 (92.9%) and the interventional techniques in 5 (83%) cases. Judging from our experience with the period of presence of the stricuture, grade of inflammation and damage of bile duct, it is suggested that choledochojejunostomy is superior to other anastomosis methods.