The morphological and histopathological assessment of Alagille syndrome with extrahepatic bile duct obstruction: the importance of the differential diagnosis with subgroup "o" biliary atresia.

PURPOSE: The differential diagnosis between Alagille syndrome (AGS) with extrahepatic bile duct obstruction (EHBDO) and biliary atresia (BA) is difficult. We report a case series of AGS with EHBDO with detailed validation of the morphological and histopathological features for the differential diagnosis of BA. METHODS: Six liver transplantations (LTs) were performed for AGS with EHBDO. All patients were diagnosed with BA at the referring institution and the diagnosis of AGS was then confirmed based on a genetic analysis before LT. We verified the morphological and histopathological findings of the porta hepatis and liver at the diagnosis of BA and at LT. RESULTS: All patients had acholic stool in the neonatal period and were diagnosed with BA by cholangiography. The gross liver findings included a smooth and soft surface, without any cirrhosis. The gross findings of the porta hepatis included aplasia of the proximal hepatic duct, or subgroup "o", in five patients. The histopathological examination of the EHBD also revealed obstruction/absence of the hepatic duct. There were no patients with aplasia of the common bile duct. CONCLUSIONS: Aplasia of the hepatic duct and the macroscopic liver findings may help in to differentiate between AGS with EHBDO and BA.

Influence of cholecystectomy on the flow dynamic pattern of bile in the extrahepatic bile duct: Assessment by cine-dynamic MRCP with spatially-selective IR pulse.

PURPOSE: To evaluate the influence of cholecystectomy on the flow dynamic pattern of bile in the extrahepatic bile duct by using cine-dynamic MRCP with spatially-selective inversion-recovery (IR) pulse non-invasively. MATERIALS AND METHODS: 56 patients with cholecystectomy and 48 control subjects without cholecystectomy who underwent cine-dynamic MRCP with spatially-selective IR pulse at 1.5 T or 3 T (TR/TE, 4000 msec/500 msec; echo train spacing, 6.5 msec; echo train length, 172; section thickness, 50 mm; matrix, 320 × 320; field of view, 320 × 320 mm; bandwidth, 488 Hz; and inversion time, 2200 msec). In cine-dynamic MRCP, IR pulse with 20 mm width was placed on the common bile duct (CBD) to evaluate the movement of bile (antegrade and reversed bile flow). Cine-dynamic MRCP imaging was scanned every 15 s (imaging, 4 s; rest, 11 s) during 5 min to acquire a series of single-shot images (a total of 20 images). The frequency that antegrade or reversed bile flow was observed in the extrahepatic bile duct, and 5-point grading score based on the moving distance of antegrade or reversed bile flow were compared between the groups. Both groups were compared using the χ2 and Mann-Whitney U tests (P < 0.05 considered significant). RESULTS: Antegrade bile flow was observed more frequently in the cholecystectomy group than in the non-cholecystectomy group (5.1 times vs. 2.8 times, P = 0.008). Mean grading score of antegrade bile flow was significantly greater in the cholecystectomy group than in the non-cholecystectomy group (mean grade, 0.33 vs 0.21; P = 0.014). Regarding reversed bile flow, there were no significant differences in the frequency and grading score between cholecystectomy group and non-cholecystectomy group. CONCLUSION: Antegrade bile flow was observed more frequently and predominantly in patients after cholecystectomy in cine-dynamic MRCP with spatially-selective IR pulse while reversed bile flow was observed equivalently.

Cost Efficacy of Metal Stents for Palliation of Extrahepatic Bile Duct Obstruction in a Randomized Controlled Trial.

BACKGROUND & AIMS: Endoscopic stents are placed for palliation of extrahepatic bile duct obstruction. Although self-expandable metal stents (SEMS) remain patent longer than plastic stents, they are more expensive. We aimed to evaluate which type of stent (plastic, uncovered SEMS [uSEMS], or partially covered SEMS [pcSEMS]) is the most effective and we assessed costs. METHODS: We performed a multicenter randomized trial in 219 patients at 18 hospitals in The Netherlands from February 2008 through February 2013. Patients were assigned randomly for placement of a plastic stent (n = 73), uSEMS (n = 75), or pcSEMS (n = 71) during endoscopic retrograde cholangiopancreatography. Patients were followed up for up to 1 year. Researchers were not blinded to groups. The main study end points included functional stent time and costs. RESULTS: The mean functional stent times were 172 days for plastic stents, 288 days for uSEMS, and 299 days for pcSEMS (P < .005 for uSEMS and pcSEMS vs plastic). The initial placement of plastic stents (€1042 or $1106) cost significantly less than placement of SEMS (€1973 or $2094) (P = .001). However, the total cost per patient at the end of the follow-up period did not differ significantly between plastic stents (€7320 or $7770) and SEMS (€6932 or $7356) (P = .61). Furthermore, in patients with short survival times (≤3 mo) or metastatic disease, the total cost per patient did not differ between plastic stents and SEMS. No differences in costs were found between pcSEMS and uSEMS. CONCLUSIONS: Although placement of SEMS (uncovered or partially covered) for palliation of extrahepatic bile duct obstruction initially is more expensive than placement of plastic stents, SEMS have longer functional time. The total costs after 1 year do not differ significantly with stent type. Dutch Clinical Trial Registration no: NTR1361.

Assessment of jaundice in the hospitalized patient.

Jaundice in the hospitalized patient is not an uncommon consultation for the general gastroenterologist. It is essential to explore the underlying cause of jaundice because management is largely aimed at addressing these causes rather than the jaundice itself. Although the diagnostic evaluation for jaundice can be broad, clinical judgment must be used to prioritize between various laboratory tests and imaging studies. Most importantly, clinicians must understand which conditions are emergent and/or require evaluation for liver transplantation. Further studies need to be performed to better understand the outcomes of hospitalized patients who develop jaundice.

Effectiveness of intraoperative cholangiography using indocyanine green (versus contrast fluid) for the correct assessment of extrahepatic bile ducts during day-case laparoscopic cholecystectomy.

INTRODUCTION: During cholecystectomy, intraoperative cholangiography using contrast fluid (IOC-CF) is still the "gold standard" for biliary tract identification but has many associated pitfalls. A new IOC technique using indocyanine green (IOC-IG) appears to be promising. Here, we studied the effectiveness of IOC-IG (vs IOC-CF) during day-case laparoscopic cholecystectomy. MATERIALS AND METHODS: Over a 6-month period, we included 23 patients (with no cirrhosis or risk factors for choledocholithiasis) scheduled for day-case laparoscopic cholecystectomy. The primary efficacy criterion was the "analyzability rate" (i.e., the ability to identify the cystic duct, the cystic duct-hepatic duct junction, and the common bile duct) for the IOC-CF and IOC-IG procedures after dissection. Indocyanine green was infused under general anesthesia. The same near-infrared laparoscopic imaging system was used for IOC-IG and conventional visual inspection. IOC-CF was always attempted after dissection. Each patient served as his/her own control. Cholecystectomies were video-recorded for subsequent off-line, blind analysis. RESULTS: The analyzability rate was 74 % for IOC-IG after dissection, 70 % for IOC-CF (p = 0.03), 26 % for conventional visual inspection, and 48 % for IOC-IG before dissection. When each IOC modality (conventional visual inspection, IOC-IG before and after dissection) was considered as a diagnostic test, the accuracy for simultaneous identification of the three anatomic elements was respectively 48, 52, and 74 %. No adverse events occurred during the IOC-IG procedure. CONCLUSION: IOC-IG was feasible and safe. Our results suggest that this technique is more effective than IOC-CF for biliary tract identification after dissection and may constitute a powerful diagnostic test for the detection of extrahepatic ducts.

Assessment of physiologic bile flow in the extrahepatic bile duct with cine-dynamic MR cholangiopancreatography and a spatially selective inversion-recovery pulse.

PURPOSE: To determine the feasibility of directly and noninvasively visualizing physiologic bile flow in the extrahepatic bile duct by means of nonpharmacologic cine-dynamic magnetic resonance (MR) cholangiopancreatography with a spatially selective inversion-recovery (IR) pulse and assess the flow dynamic pattern of bile in the extrahepatic bile duct. MATERIALS AND METHODS: The institutional review board approved this retrospective study and waived the need for informed consent. Thirty-five patients without known pancreatobiliary diseases and 11 patients with dilatation of the extrahepatic bile duct were included. Cine-dynamic MR cholangiopancreatography with a spatially selective IR pulse was performed by imaging every 15 seconds over a 5-minute interval (20 images acquired total). The images were evaluated for the visualization of bile flow, the frequency that bile flow was observed in the extrahepatic bile duct, and the distance the bile moved within the area of the IR pulse. Statistical analysis was performed by using Spearman rank correlation coefficient and Mann-Whitney U tests. RESULTS: Antegrade bile flow was observed in 29 of 35 patients (83%) in the nondilated group. Bile flow was observed much more frequently in the nondilated group than in the dilated group (4.4 times vs 1.8 times, P = .029). The distance that bile moved forward within the area of the IR pulse was significantly greater in the nondilated group than in the dilated group (mean grade, 0.44 vs 0.14; P = .033), suggesting stagnation or slowdown of antegrade bile flow in patients with biliary dilatation. Reversed bile flow was also observed in 26 of 35 patients (74%) in the nondilated group without biliary diseases. CONCLUSION: Nonpharmacologic cine-dynamic MR cholangiopancreatography with a spatially selective IR pulse allows direct and noninvasive visualization of bile flow in the extrahepatic bile duct, demonstrating that reversed bile flow is a physiologic phenomenon.

Adequate lymph node assessment for extrahepatic bile duct adenocarcinoma.

OBJECTIVE: To examine the importance of adequate lymph node sampling in staging of extrahepatic bile duct cancer (EHBDCA). SUMMARY OF BACKGROUND DATA: The American Joint Committee on Cancer staging manual (sixth edition) states that histologic examination of at least 3 lymph nodes is required for adequate N stage determination for EHBDCA. This recommendation has not been validated; however, there has been no comparative assessment of the proximal versus distal bile duct cancer. METHODS: A total of 257 patients (144 hilar cholangiocarcinoma [HCCA] and 113 distal bile duct adenocarcinoma [DBDCA]) who underwent curative intent resection (1987-2007) were analyzed; patients with gallbladder cancer were excluded. Final disease staging, including lymph node status and total number of nodes examined (total lymph node count), was obtained from the final pathology report. Differences in disease-specific survival, according to nodal status, were compared using the log-rank test. R1 resections (n = 51) were excluded from this analysis. RESULTS: Metastasis to regional lymph nodes was noted in 89 patients (34.6%) and was an independent prognostic factor of poor survival (median disease-specific survival N0 vs. N1: 53.5 vs. 19.3 months, P < 0.0001, hazard ratio = 2.1 [95% CI: 1.4-3.2]). The median total lymph node count was 6 (range: 0-42), and was significantly lower for HCCA compared with DBDCA (median = 3 [range: 0-16] vs. 12 [range: 1-42], P < 0.001, respectively). For the entire cohort, patients who underwent R0 resection and were classified as N0, based on total lymph node count <11, had a disease-specific survival that was significantly worse than that of patients classified as N0 based on total lymph node count >or=11 (52.6 +/- 9.8 months vs. not reached, P = 0.008). The estimated optimal total lymph node count for HCCA differed from that of DBDCA (n = 7 vs. n = 11, respectively). CONCLUSIONS: Adequate lymph nodes assessment of EHBDCA, based on the current AJCC recommendations, results in understaging of these tumors. With respect to the optimal total lymph node count, HCCA, and DBDCA should be considered separately.

Percutaneous treatment of malignant jaundice due to extrahepatic cholangiocarcinoma: covered Viabil stent versus uncovered Wallstents.

To compare clinical effectiveness of Viabil-covered stents versus uncovered metallic Wallstents, for palliation of malignant jaundice due to extrahepatic cholangiocarcinoma, 60 patients were enrolled in a prospective and randomized study. In half of the patients a bare Wallstent was used, and in the other half a Viabil biliary stent. Patients were followed up until death. Primary patency, survival, complication rates, and mean cost were calculated in both groups. Stent dysfunction occurred in 9 (30%) patients in the bare stent group after a mean period of 133.1 days and in 4 (13.3%) patients in the covered stent group after a mean of 179.5 days. The incidence of stent dysfunction was significantly lower in the covered stent group (P = 0.046). Tumor ingrowth occurred exclusively in the bare stent group (P = 0.007). Median survival was 180.5 days for the Wallstent and 243.5 days for the Viabil group (P = 0.039). Complications and mean cost were similar in the two groups. Viabil stent-grafts proved to be significantly superior to Wallstents for the palliation of malignant jaundice due to extrahepatic cholangiocarcinoma, with comparable cost and complication rates. Appropriate patient selection should be performed prior to stent placement.

Prognostic assessment of three single-nucleotide polymorphisms (GNB3 825C>T, BCL2-938C>A, MCL1-386C>G) in extrahepatic cholangiocarcinoma.

BACKGROUND/AIMS: Cholangiocellular carcinoma (CCA) has a devastating prognosis and markers enabling a precise prediction of the clinical outcome have long remained scarce. Recently, it has been demonstrated that genotype distribution of several single-nucleotide polymorphisms (SNPs) in genes that modulate G protein-signal transduction and apoptosis can serve as helpful predictive parameters in various carcinomas. We here aimed at extending the panel of SNPs suitable for predicting the outcome of CCA. METHODOLOGY: Forty Caucasian patients with extrahepatic CCA and 40 age- and sex-matched healthy white Caucasians were genotyped to elucidate putative associations between clinical outcome and genotypes of the three following SNPs: G protein beta 3 (GNB3) 825C>T, B-cell-lymphoma-2 (Bcl-2) -938C>A, and myeloid cell leukemia-1 (Mcl-1) -386C>G. RESULTS: Patients homozygous for the C allele of the GNB3 825C>T polymorphism exhibited a significant prolonged overall survival compared with patients displaying the CT or TT genotype (median survival [months]: 31 vs. 13 vs. 7; p < .05) and also showed lower bilirubin serum levels. Additionally, the CC genotype of the BCL2-938C>A polymorphism was associated with higher GLDH serum activities (U/l; 29.8 +/- 7.1 vs. 11.4 +/- 4.3 vs. 5.6 +/- 1.7 comparing CC vs. CA vs. AA; p < .05). Genotype distributions for all SNPs were not significantly different in patients vs. controls. CONCLUSIONS: GNB3 825C>T SNP may be a novel independent prognostic marker for patients suffering from extrahepatic CCA with the CC genotype to be associated with a favorable clinical outcome. Further prospective studies are needed to confirm these results and reveal additional functional SNP effects.

Real-time intraoperative assessment of the extrahepatic bile ducts in rats and pigs using invisible near-infrared fluorescent light.

BACKGROUND: Currently, only x-ray fluoroscopy is available for visualization of the extrahepatic bile ducts intraoperatively. We hypothesized that with an appropriate fluorophore and imaging system, invisible near-infrared (NIR) light could be used for image-guided procedures on the extrahepatic bile ducts. METHODS: We quantified the performance of three 800 nm NIR fluorophores, differing primarily in their degree of hydrophilicity, for real-time imaging of the extrahepatic bile ducts in rats and pigs: IR-786, indocyanine green (ICG), and the carboxylic form of IRDyetrade mark 800CW (CW800-CA). The signal-to-background ratio (SBR) of the common bile duct relative to liver and pancreas was measured as a function of the dose of contrast agent, injection site, and kinetics using an intraoperative NIR fluorescence imaging system described previously. Bile samples were examined by high performance liquid chromatography tandem mass spectrometry (HPLC/MS) to determine the chemical form of fluorophores in bile. RESULTS: Non-sulfonated (IR-786) and di-sulfonated (ICG) NIR fluorophores had poor efficiency and kinetics of excretion into bile. Tetra-sulfonated CW800-CA, however, provided sensitive, specific, and real-time visualization of the extrahepatic bile ducts after a single low-dose given either intraportally or intravenously via systemic vein. A SBR >/=2 provided sensitive assessment of extrahepatic bile duct anatomy and function for over 30 min post-injection, including the detection of millimeter-sized, radiolucent inclusions in pigs. CW800-CA remained intact chemically after secretion into bile. CONCLUSION: The combination of invisible NIR light and an IV injection of CW800-CA provides prolonged, real-time visualization of the extrahepatic bile duct, without ionizing radiation and without changing the look of the operative field.

[Assessment of the value of PEF (cisplatin, epirubicin, 5 fluorouracil) in advanced extrahepatic biliary tract and pancreatic cancer]. / Ocena wartosci chemioterapii paliatywnej PEF (cisplatyna, epirubicyna, 5-fluorouracyl) w zaawansowanych rakach zewnatrzwatrobowych dróg zólciowych i trzustki.

INTRODUCTION: Extrahepatic biliary tract and pancreatic cancer are relatively rare malignant tumors. Prognosis is usually poor and surgical treatment gives a chance of cure in nonadvanced cases only. THE AIM OF THIS STUDY: Evaluation of efficacy and toxicity of PEF regimen (cisplatin + epirubicin + 5 fluorouracil) in advanced extrahepatic biliary tract and pancreatic cancer. MATERIAL AND METHODS: Chemotherapy regimen: cisplatin 20 mg/m2 i.v, epirubicin 25 mg/m2 i.v., 5 fluorouracil was given in 28 patients with advanced extrahepatic biliary tract and pancreatic cancer at the Clinic of Oncology of the Collegium Medicum of the Jagiellonian University in Krakow in years 1997 to 2004. The treatment was repeated every 4 weeks up to 6 cycles. 12 patients with extrahepatic biliary tract cancer and 16 patients with pancreatic cancer were treated. RESULTS: Median time from the diagnosis to death was 8.8 months in patients with extrahepatic biliary tract and 8.7 months in patients with pancreatic cancer. 1-year survival was 25% and 16.7%, respectively. Hematological toxicity G 3 and G 4 occured in 5 patients (17.9% treated). CONCLUSIONS: Chemotherapy PEF seems to be an active and well tolerated regimen of palliative chemotherapy for advanced extrahepatic biliary tract carcinomas and pancreas carcinomas. Overall survival in the pancreatic cancer group is comparable to results obtained with gemcitabine monotherapy.

[Assessment of the definition of early extrahepatic bile duct cancer through the prognosis analysis who had received curative resection].

BACKGROUND/AIMS: The definition of early extrahepatic bile duct cancer might be different from that of other gastrointestinal cancer because of the differences of histologic features including the lack of muscularis mucosa and submucosal layer in bile duct. The purpose of this study was to evaluate the concept of early extrahepatic bile duct cancer in Korea. METHODS: We evaluated seventynine cases of extrahepatic bile duct cancer who had received curative resection in Severence Hospital, Yonsei University from March 1986 to October 2005. We retrosptectively reviewed the medical records and analyzed variable prognostic factors to define early extrahepatic bile duct cancer. RESULTS: Invasion limited to the mucosa was noted in 5 cases (6.3%), fibromuscular layer in 12 cases (15.2%), adventitia of fibromuscular layer and serosa in 26 cases (32.9%), and invasion of adjacent organs in 36 cases (45.6%). Disease free 5-year survival according to the depth of invasion were 80.7% in tumor confined within mucosa, 80.0% within fibromuscular layer, 57.2% within adventitia of fibromuscular layer and serosa, and 51.5% in tumor with invasion of adjacent organ. There was no significant difference in the survival rate between patients with tumor confined to mucosa and patients with tumor invasion limited to the fibromuscular layer. However, the survival rate of patients with tumor limited to the mucosa or fibromuscular layer was significantly higher than that of patients with tumor invaded beyond fibromusular layer. In early cancer, there were more papillary polypoid type in gross finding and papillary adenocarcinoma in pathologic finding when compared to advanced cancer. CONCLUSIONS: Early extrahepatic bile duct cancer can be defined as the tumor invasion limited to the mucosa and fibromuscular layer.

Assessment of hilar and extrahepatic bile duct cancer using multidetector CT: value of adding multiplanar reformations to standard axial images.

To retrospectively assess the value of multiplanar reformations (MPRs) compared with standard axial images in the assessment of hilar and extrahepatic bile duct cancer. Forty-eight patients with confirmed bile duct cancer were included as preoperative work-ups; all of these patients underwent contrast-enhanced multidetector CT consisting of axial and MPR images. Two radiologists independently assessed the axial images alone and the combined axial and MPR images in the coronal and sagittal planes for the presence of tumor, its extent, vascular involvement, and resectability. The results were compared with surgical and pathologic findings. For tumor presence and conspicuity, combined axial and MPR images had higher values than the axial only images. For evaluation of tumoral extent, there was no difference between the two image sets for either reader. The accuracy for tumor extent was lower in hilar cancer than in extrahepatic bile duct cancer. For evaluation of vascular involvement and resectability, the area under the receiver operating characteristic curve of axial images was not significantly different from that of the reformatted images. The addition of MPR images to the standard axial images did not significantly improve the diagnostic performance of MDCT in the evaluation of the bile duct cancer.

Preoperative assessment of the aberrant bile duct using multislice computed tomography cholangiography.

BACKGROUND: This study aimed to determine the frequency of anatomic variations of bile ducts (aberrant bile ducts) using multislice helical computed tomography (MCT) cholangiography. METHODS: MCT scanning was performed after slow infusion of 100 mL meglumine iotroxate. Overlapping axial images, taken at 0.5-mm intervals, were reconstructed to create a multiplanar reconstruction with volume rendering. We analyzed anatomical variations of the biliary tree by MCT cholangiography. RESULTS: In a total of 113 patients, MCT cholangiography provided clear images of aberrant bile ducts in 18 patients. Major type (draining a particular segment of the liver) was found in 9 cases (8%) and minor type (draining a particular subsegment of the liver) in 9 cases (8%). CONCLUSIONS: Preoperative MCT cholangiography provides important information about the precise biliary anatomy and can reveal unexpected aberrant bile ducts prior to biliary surgery, especially laparoscopic cholecystectomy.

Usual and unusual causes of extrahepatic cholestasis: assessment with magnetic resonance cholangiography and fast MRI.

Cholestasis may result from hepatocellular (intrahepatic) disease or biliary tract (extrahepatic) abnormalities. Etiologies causing extrahepatic cholestasis are extremely diverse and invasive procedures, such as endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic cholangiography (PTC), were previously required to establish the diagnosis. Due to refinements of magnetic resonance imaging (MRI) techniques, the patient with extrahepatic cholestasis currently can be evaluated noninvasively, and the information revealed frequently exceeds the findings obtained by ERCP and PTC. In this essay, we illustrate the classic MR cholangiographic (MRC) and MRI features of a variety of disorders causing extrahepatic cholestasis, including non-neoplastic disorders of the biliary tract (congenital abnormalities, infectious processes, iatrogenic disorders, and postsurgical complications) and neoplastic conditions (e.g., tumors of the pancreas, biliary tree, liver, ampulla, and regional lymph nodes). In most cases, familiarity with the key MRC features in addition to information obtained via cross-sectional MR images provide sufficient information for adequate lesion characterization.

Quality-of-life assessment of surgical reconstruction after laparoscopic cholecystectomy-induced bile duct injuries: what happens at 5 years and beyond?

HYPOTHESIS: Quality of life of patients after biliary reconstruction for laparoscopic injuries is comparable to that of patients after laparoscopic cholecystectomy. DESIGN: Outcomes study. SETTING: Tertiary referral center. PATIENTS: Records of 59 consecutive patients undergoing surgical reconstruction of the biliary tract after injury induced by laparoscopic cholecystectomy between 1990 and 1997 were reviewed. Hepp-Couinaud technique or Roux-en-Y hepaticojejunostomy was used in 53 patients; other procedures included cholangiojejunostomy, choledochorrhaphy, and hepaticoduodenostomy. INTERVENTIONS: Quality-of-life questionnaires (36-Item Short-Form Health Survey [SF-36]) were mailed to each patient in the group and to patients who underwent uneventful laparoscopic cholecystectomy, matched individually by year, sex, and age group. Values from the general population matched by age and sex were gathered (national norms). Minimum time of follow-up was 5 years. RESULTS: Eighty-nine (81%) of 110 potential respondents to the survey completed the SF-36 questionnaires. All 8 values evaluated in the SF-36 questionnaire (physical functioning, role-physical, bodily pain, general health perceptions, vitality, social functioning, role-emotional, and mental health index) for patients undergoing biliary reconstruction were similar to those of both their matched controls (all P >.10) and national norms (all P >.05). The standardized physical component scale was also similar between the 2 groups (cases vs controls, 51 vs 48; P =.47), as was the standardized mental component scale (cases vs controls, 55 vs 55; P =.60). CONCLUSIONS: With a minimum of 5 years of follow-up, the quality of life after surgical biliary reconstruction compares favorably with that of both patients undergoing uneventful laparoscopic cholecystectomy and national norms.