Assessment of a novel biliary-specific near-infrared fluorescent dye (BL-760) for intraoperative detection of bile ducts and biliary leaks during hepatectomy in a preclinical swine model.

OBJECTIVES: Postoperative bile leakage is a common complication of hepatobiliary surgery and frequently requires procedural intervention. Bile-label 760 (BL-760), a novel near-infrared dye, has emerged as a promising tool for identifying biliary structures and leakage, owing to its rapid excretion and strong bile specificity. This study aimed to assess the intraoperative detection of biliary leakage using intravenously administered BL-760 compared with intravenous (IV) and intraductal (ID) indocyanine green (ICG). MATERIALS AND METHODS: Laparotomy and segmental hepatectomy with vascular control were performed on two 25-30 kg pigs. ID ICG, IV ICG, and IV BL-760 were administered separately, followed by an examination of the liver parenchyma, cut liver edge, and extrahepatic bile ducts for areas of leakage. The duration of intra- and extrahepatic fluorescence detection was assessed, and the target-to-background (TBR) of the bile ducts to the liver parenchyma was quantitatively measured. RESULTS: In Animal 1, after intraoperative BL-760 injection, three areas of leaking bile were identified within 5 min on the cut liver edge with a TBR of 2.5-3.8 that was not apparent to the naked eye. In contrast, after IV ICG administration, the background parenchymal signal and bleeding obscured the areas of bile leakage. A second dose of BL-760 demonstrated the utility of repeated injections, confirming two of the three previously visualized areas of bile leakage and revealing one previously unseen leak. In Animal 2, neither ID ICG nor IV BL-760 injections showed obvious areas of bile leakage. However, fluorescence signals were observed within the superficial intrahepatic bile ducts after both injections. CONCLUSIONS: BL-760 enables the rapid intraoperative visualization of small biliary structures and leaks, with the benefits of fast excretion, repeatable intravenous administration, and high-fluorescence TBR in the liver parenchyma. Potential applications include the identification of bile flow in the portal plate, biliary leak or duct injury, and postoperative monitoring of drain output. A thorough assessment of the intraoperative biliary anatomy could limit the need for postoperative drain placement, a possible contributor to severe complications and postoperative bile leak.

Longitudinal Assessment of Bile Duct Loss in Primary Biliary Cholangitis.

INTRODUCTION: Bile duct involvement is a key finding of primary biliary cholangitis (PBC). The aim of this study was to evaluate baseline ductopenia and disease progression. METHODS: Retrospective longitudinal histological follow-up of treatment-naive patients with PBC. RESULTS: Eighty-three patients were included, with ductopenia correlated to fibrosis stage at baseline. The cumulative incidence of severe ductopenia remained stable after 5 years, whereas fibrosis continually increased over time. Baseline AST-to-Platelet Ratio Index and elevated alkaline phosphatase >2 times the normal with abnormal bilirubin were associated with ductopenia progression. DISCUSSION: Bile duct injury does not seem to follow the same course as fibrosis in PBC.

Routine versus selective intraoperative cholangiography during cholecystectomy: systematic review, meta-analysis and health economic model analysis of iatrogenic bile duct injury.

BACKGROUND: Bile duct injury (BDI) is a severe complication following cholecystectomy. Early recognition and treatment of BDI has been shown to reduce costs and improve patients' quality of life. The aim of this study was to assess the effect and cost-effectiveness of routine versus selective intraoperative cholangiography (IOC) in cholecystectomy. METHODS: A systematic review and meta-analysis, combined with a health economic model analysis in the Swedish setting, was performed. Costs per quality-adjusted life-year (QALY) for routine versus selective IOC during cholecystectomy for different scenarios were calculated. RESULTS: In this meta-analysis, eight studies with more than 2 million patients subjected to cholecystectomy and 9000 BDIs were included. The rate of BDI was estimated to 0.36 per cent when IOC was performed routinely, compared with to 0.53 per cent when used selectively, indicating an increased risk for BDI of 43 per cent when IOC was used selectively (odds ratio 1.43, 95 per cent c.i. 1.22 to 1.67). The model analysis estimated that seven injuries were avoided annually by routine IOC in Sweden, a population of 10 million. Over a 10-year period, 33 QALYs would be gained at an approximate net cost of €808 000 , at a cost per QALY of about €24 900. CONCLUSION: Routine IOC during cholecystectomy reduces the risk of BDI compared with the selective strategy and is a potentially cost-effective intervention.

Assessment of biliary anatomy in potential living liver donors: Added value of gadoxetic acid-enhanced T1 MR Cholangiography (MRC) including utilization of controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA) technique in comparison to T2W-MRC.

OBJECTIVES: To assess the added value of gadoxetic-acid-enhanced T1-weighted magnetic resonance Cholangiography (T1W-MRC) including controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA)-Volumetric Interpolated Breathhold (VIBE) technique compared to T2-weighted MR Cholangiography (T2W-MRC) in depicting biliary anatomy in potential living liver donors. METHODS: Eighty-five potential donors including 34 men with a mean age of 35.6 years (range, 18-55 years) and 51 women with a mean age of 36.7 years (range, 23-57 years), were enrolled in this ethics-approved retrospective study. Image quality for depiction of bile ducts was evaluated by two readers in consensus in 3 separate reading sessions: 1) T2W-MRC alone, 2) T1W-MRC alone (including CAIPI-VIBE and generalized autocalibrating partially parallel acquisitions (GRAPPA)-VIBE techniques, and 3) combined T1W/T2W-MRC. Accuracy of T2W-MRC, T1W-MRC, and combined T1W/T2W-MRC for the identification/classification of the biliary variants was calculated using intraoperative cholangiogram (IOC) as the reference standard. Image quality and reader diagnostic confidence provided by CAIPI-VIBE technique was compared with GRAPPA-VIBE technique. Datasets were compared using the Wilcoxon signed-rank test. RESULTS: Image quality for depiction of the bile ducts was significantly superior in the combined T1W/T2W-MRC group, when compared to each of T2W-MRC and T1W-MRC groups independently (P value = 0.001-0.034). The combination of CAIPI-VIBE and GRAPPA-VIBE was superior compared to each of the sequences individually. The accuracy of T2W-MRC and T1W-MRC was 93% and 91%, respectively. T1W-MRC depicted four biliary variants better than T2W-MRC. Two variants not well seen in T2W-MRC were clearly shown on T1W-MRC. CONCLUSION: Gadoxetic-acid-enhanced T1W-MRC and conventional T2W-MRC techniques are complementary for depiction of biliary variants in potential liver donors and the combination of the two improves the results. The combination of CAIPI-VIBE and GRAPPA-VIBE techniques appear to be complementary for optimal diagnostic yield of T1W-MRC.

Assessment of quiet T2 weighted PROPELLER sequence in pediatric abdominal imaging.

INTRODUCTION: Elevated acoustic noise during Magnetic Resonance Imaging (MRI) has been associated with patient anxiety and altered cochlear function. Acoustic Reduction Technique (ART) T2 weighted (T2w) periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) has been studied in brain MR but not abdominopelvic imaging. The purpose of our study was to evaluate the image quality and acoustic noise level of ART T2w PROPELLER sequence in comparison with the conventional T2w PROPELLER sequence in pediatric abdomino-pelvic imaging. METHODS: Eleven consecutive pediatric patients undergoing abdomino-pelvic MRI were scanned on a 3 Tesla magnet using standard and ART T2w PROPELLER sequences. After scanning completion, objective sound level measurements were performed with a sound level meter and microphone. Mann-Whitney U test was used for a non-parametric two-tailed statistical analysis of acoustics, image rating and scan time with significance level set to 0.05. Overall inter-rater agreement was calculated using Cohen's kappa coefficient. RESULTS: Eleven pediatric patients (4 females and 7 males) between 26 days and 18 years of age (mean = 10.0, SD = 5.8) were included. ART T2w produced lower levels of acoustic noise than standard technique in a comparison of mean decibel readings from eleven trials of standard and ART T2w (p value = 0.00008). Streak artifacts were rated greater in ART T2w by both raters (p-value = 0.00278 and 0.00252). There was no significant difference in bile duct blurring, respiratory ghosting, pulsation, fat suppression or hepatic parenchymal depiction. CONCLUSION: Presence of additional streaking artifacts should be considered along with the benefit of reduced acoustic noise from ART T2w.

Assessment of Duodenal Diverticula: Computed Tomography Findings.

AIMS: To demonstrate the prevalence, accompanying pathologies, imaging and follow up findings of Duodenal Diverticula (DD) with Multidetector Computed Tomography (MDCT). MATERIALS AND METHODS: Consecutive 2910 abdominal MDCTs were retrospectively reviewed on axial, coronal and sagittal planes. DD were evaluated for prevalence, location, number, size, contents, diverticular neck, accompanying pancreaticobiliary pathologies, jejunal and colonic diverticula, respectively. RESULTS: DD were diagnosed in 157 cases (5.4%) and found mostly in the second part of the duodenum. Juxta-ampullary DD was the most common type (78.3%) and mostly located ventral (n:86, 69.9%) to the ampulla of Vater. DD was solitary in 123 patients (78.3%) and more than one in 34 patients (21.7%). The median diameter of DD was 2.5 cm (range 1.5-3.6 cm) in the long-axis. The lumen of DD contains air and contrast agent (n:96, 61.1%); air, contrast agent and debris (n:42, 26.7%) in most cases. Colonic diverticula (n:36, 22.9%), cholelithiasis (n:32, 20.4%), choledocholithiasis (n:7, 4.4%), and biliary dilatation (n:8, 5.1%) were the most common additional findings. Median follow-up time was 23 months (range 11 to 41 months). In three cases, new findings (cholelithiasis, n:3, choledocholithiasis, n:1) were detected. CONCLUSION: Accompanying pathologies with DD diagnosis are valuable for physicians in order to manage the patients. Following clinical and radiological features of well-diagnosed DD might reduce the possible complications.

Biliary complications after liver transplantation: Assessment with MR cholangiopancreatography and MR imaging at 3T device.

PURPOSE: Our study was aimed to assess the diagnostic value of MR cholangiopancreatography (MRCP) and MR imaging at 3 T device when evaluating biliary adverse events after liver transplantation. MATERIALS AND METHODS: A series of 384 MR examinations in 232 liver transplant subjects with suspected biliary complications (impaired liver function tests and/or biliary abnormalities on ultrasound) were performed at 3 T device (GE-DISCOVERY MR750; GE Healthcare). After the acquisition of axial 3D dual-echo T1-weighted images and T2-weighted sequences (propeller and SS-FSE), MRCP was performed through coronal thin-slab 3D-FRFSE and coronal oblique thick-slab SSFSE T2w sequences. DW-MRI of the liver was performed using an axial spin-echo echo-planar sequence with multiple b values (150, 500, 1000, 1500 s/mm2) in all diffusion directions. Contrast-enhanced MRCP was performed in 25/232 patients. All MR images were blindly evaluated by two experienced abdominal radiologists in consensus to determine the presence of biliary complications, whose final diagnosis was based on direct cholangiography, surgery and integrating clinical follow-up with ultrasound and/or MRI findings. RESULTS: In 113 patients no biliary abnormality was observed. The remaining 119 subjects were affected by one or more of the following complications: non-anastomotic strictures including typical ischemic-type biliary lesions (n = 67), anastomotic strictures (n = 34), ampullary dysfunction (n = 4), anastomotic leakage (n = 4), stones, sludge and casts (n = 65), vanishing bile duct (n = 1). The sensitivity, specificity, PPV, NPV and diagnostic accuracy of the reviewers for the detection of all types of biliary complications were 99%, 96%, 95%, 99% and 97%, respectively. CONCLUSION: MR cholangiopancreatography and MR imaging at 3 T device are extremely reliable for detecting biliary complications after liver transplantation.

MRI-based decision tree model for diagnosis of biliary atresia.

OBJECTIVES: To evaluate MRI findings and to generate a decision tree model for diagnosis of biliary atresia (BA) in infants with jaundice. METHODS: We retrospectively reviewed features of MRI and ultrasonography (US) performed in infants with jaundice between January 2009 and June 2016 under approval of the institutional review board, including the maximum diameter of periportal signal change on MRI (MR triangular cord thickness, MR-TCT) or US (US-TCT), visibility of common bile duct (CBD) and abnormality of gallbladder (GB). Hepatic subcapsular flow was reviewed on Doppler US. We performed conditional inference tree analysis using MRI findings to generate a decision tree model. RESULTS: A total of 208 infants were included, 112 in the BA group and 96 in the non-BA group. Mean age at the time of MRI was 58.7 ± 36.6 days. Visibility of CBD, abnormality of GB and MR-TCT were good discriminators for the diagnosis of BA and the MRI-based decision tree using these findings with MR-TCT cut-off 5.1 mm showed 97.3 % sensitivity, 94.8 % specificity and 96.2 % accuracy. CONCLUSIONS: MRI-based decision tree model reliably differentiates BA in infants with jaundice. MRI can be an objective imaging modality for the diagnosis of BA. KEY POINTS: • MRI-based decision tree model reliably differentiates biliary atresia in neonatal cholestasis. • Common bile duct, gallbladder and periportal signal changes are the discriminators. • MRI has comparable performance to ultrasonography for diagnosis of biliary atresia.

Prediction of the histopathologic findings of intrahepatic cholangiocarcinoma: qualitative and quantitative assessment of diffusion-weighted imaging.

OBJECTIVE: To correlate qualitative and quantitative diffusion weighted imaging (DWI) characteristics of intrahepatic cholangiocarcinoma (ICC) with histopathologic tumour grade and fibrosis content. METHODS: Fifty-one patients (21M/30F; mean age 61y) with ICC and MRI including DWI were included in this IRB-approved multicentre retrospective study. Qualitative tumour features were assessed. Tumour apparent diffusion coefficient (ADC) mean, minimum, and normalized (nADCliver) values were computed. Tumour grade [well(G1), moderately(G2), or poorly differentiated(G3)] and tumour fibrosis content [minimal(1), moderate(2), or abundant(3)] were categorized pathologically. Imaging findings and ADC values were compared with pathologic measures. Utility of ADC values for predicting tumour grade was assessed using ROC analysis. RESULTS: 51 ICCs (mean size 6.5±1.1 cm) were assessed. 33/51(64%) of ICCs demonstrated diffuse hyperintensity and 15/51(29%) demonstrated target appearance on DWI. Infiltrative morphology (p=0.02) and tumour size (p=0.04) were associated with G3. ADCmean and nADCmean of G3 (1.32±0.47x10-3 mm2/sec and 0.97±0.95) were lower than G1+G2 (1.57±0.39x10-3 mm2/sec and 1.24±0.49; p=0.03 and p=0.04). ADCmean and nADCmean were inversely correlated with tumour grade (p<0.025). No correlation was found between ADC and tumour fibrosis content. AUROC, sensitivity and specificity of nADCmean for G3 versus G1+G2 were 0.71, 89.5% and 55.5%. CONCLUSION: ADC quantification has reasonable accuracy for predicting ICC grade. KEY POINTS: • ADC quantification was useful for predicting ICC tumour grade. • Infiltrative tumour morphology and size were associated with poorly differentiated ICCs. • ADC values depended more on ICC tumour grade than fibrosis content. • Ability to predict ICC tumour grade non-invasively could impact patient management.

Functional assessment of hepatobiliary secretion by 11C-cholylsarcosine positron emission tomography.

Positron emission tomography (PET) with 11C-cholylsarcosine (11C-CSar), a radiolabelled synthetic N-methylglycine (sarcosine) conjugate of cholic acid, is a novel molecular imaging technique that enables quantitative assessment of the individual transport steps involved in hepatic secretion of conjugated bile acids. Here, we present the method and discuss its potential clinical and scientific applications based on findings in the first human study of healthy subjects and patients with cholestasis. We also present a clinical example of a patient studied during and six months after an episode of drug-induced cholestatic liver injury.

Financial Aspects of Bile Duct Injuries.

BACKGROUND Major bile duct injury is the most worrisome complication of cholecystectomy. There is no detailed data about the incidence or treatment-related costs of bile duct injuries in Turkey. We aimed to determine prevalence and therapeutic costs of patients with major biliary duct injuries managed in our department, and further estimate a projection of these parameters at the national level. MATERIAL AND METHODS All patients admitted due to bile duct injury during cholecystectomy from 2011 to 2014 were included. Healthcare costs were calculated by summing of their all treatment-related costs in Istanbul Medical Faculty. We collected 2014-2015 data on number of patients diagnosed with cholecystitis in Turkey, the number of cholecystectomies, and the number of the interventions performed following these initial surgeries, which were obtained from the Turkish Social Security Institution. RESULTS Forty-nine patients were enrolled and bilioenteric diversion was performed in 39 patients: 20.4% of patients had Bismuth II, 38.8% had Bismuth III, and 40.8% had Bismuth IV biliary stricture. Comparison of stricture types with total costs, days of hospitalization, and outpatient clinic costs revealed significant differences. Mean total cost of corrective surgeries was 9199 TRY. We estimated that 1.5% to 2.4% of patients who underwent cholecystectomy in Turkey have bile duct injury (including 0.3% with major bile duct injury). CONCLUSIONS New preventive strategies should be used to avoid bile duct injuries, which have a huge financial impact on the national economy.

Evaluating a preoperative protocol that includes magnetic resonance imaging for lymph node metastasis in the Cholangiocarcinoma Screening and Care Program (CASCAP) in Thailand.

BACKGROUND: Treatment planning especially liver resection in cholangiocarcinoma (CCA) depends on the extension of tumor and lymph node metastasis which is included as a key criterion for operability. Magnetic resonance imaging (MRI) offers a rapid and powerful tool for the detection of lymph node metastasis (LNM) and in the current manuscript is assessed as a critical tool in the preoperative protocol for liver resection for treatment of CCA. However, the accuracy of MRI to detect LNM from CCA had yet to be comprehensively evaluated. METHODS: The accuracy of MRI to detect LNM was assessed in a cohort of individuals with CCA from the Cholangiocarcinoma Screening and Care Program (CASCAP), a screening program designed to reduce CCA in Northeastern Thailand by community-based ultrasound (US) for CCA. CCA-positive individuals are referred to one of the nine tertiary centers in the study to undergo a preoperative protocol that included enhanced imaging by MRI. Additionally, these individuals also underwent lymph node biopsies for histological confirmation of LNM (the "gold standard") to determine the accuracy of the MRI results. RESULTS: MRI accurately detected the presence or absence of LNM in only 29 out of the 51 CCA cases (56.9%, 95% CI 42.2-70.7), resulting in a sensitivity of 57.1% (95% CI 34.0-78.2) and specificity of 56.7% (95% CI 37.4-74.5), with positive and negative predictive values of 48.0% (95% CI 27.8-68.7) and 65.4% (95% CI 44.3-82.8), respectively. The positive likelihood ratio was 1.32 (95% CI 0.76-2.29), and the negative likelihood ratio was 0.76 (95% CI 0.42-1.36). CONCLUSIONS: MRI showed limited sensitivity and a poor positive predictive value for the diagnosis of LNM for CCA, which is of particular concern in this resource-limited setting, where simpler detection methods could be utilized that are more cost-effective in this region of Thailand. Therefore, the inclusion of MRI, a costly imaging method, should be reconsidered as part of protocol for treatment planning of CCA, given the number of false positives, especially as it is critical in determining the operability for CCA subjects.

Routine intraoperative cholangiography during cholecystectomy is a cost-effective approach when analysing the cost of iatrogenic bile duct injuries.

BACKGROUND: The total cost of bile duct injuries (BDIs) in an unselected national cohort of patients undergoing cholecystectomy are unknown. The aim was to evaluate costs associated with treatment of cholecystectomy-related BDIs and to calculate cost effectiveness of routine vs. on-demand intraoperative cholangiography (IOC). METHODS: Data from Swedish patients suffering a BDI during a 5 year period were analysed. Questionnaires to investigate loss-of-production and health status (EQ-5D) were distributed to patients who suffered a BDI during cholecystectomy and who underwent uneventful cholecystectomy (matched control group). Costs per quality-adjusted-life-year (QALY) gained by intraoperative diagnosis were estimated for two strategies: routine versus on-demand IOC during cholecystectomy. RESULTS: Intraoperative diagnosis, immediate intraoperative repair, and minor BDI were all associated with reduced direct treatment costs compared to postoperative diagnosis, delayed repair, and major BDI (all p < 0.001). No difference was noted in loss-of-production for minor versus major BDIs or between different treatment strategies. The cost per QALY gained with routine intraoperative cholangiography (ICER-incremental cost-effectiveness ratio) to achieve intraoperative diagnosis was €50,000. CONCLUSIONS: Intraoperative detection and immediate intraoperative repair is the superior strategy with less than half the cost and superior functional patient outcomes than postoperative diagnosis and delayed repair. The cost per QALY gained (ICER) using routine IOC was considered reasonable.

Role of contrast enhanced ultrasound in the assessment of biliary duct disease.

The introduction of microbubble contrast agents (CA), which act as blood pool tracers, has overcome the limitations of conventional B-Mode, colour or power Doppler ultrasound, enabling the display of parenchymal microvasculature. Initially, the use of CA was accepted for hepatic lesions. In the following years, experts have expanded recommendations, as a result of the method's efficiency in extrahepatic applications. In this article we review the methodology and the application of contrast-enhanced ultrasound (CEUS) in the evaluation of biliary pathology. This new imaging tool allows a non invasive differential diagnosis of biliary lesions and a clearer delineation of the tumoral process.

Endoscopic ultrasonography guided biliary drainage: summary of consortium meeting, May 7th, 2011, Chicago.

Endoscopic retrograde cholangiopancreatography (ERCP) has become the preferred procedure for biliary or pancreatic drainage in various pancreatico-biliary disorders. With a success rate of more than 90%, ERCP may not achieve biliary or pancreatic drainage in cases with altered anatomy or with tumors obstructing access to the duodenum. In the past those failures were typically managed exclusively by percutaneous approaches by interventional radiologists or surgical intervention. The morbidity associated was significant especially in those patients with advanced malignancy, seeking minimally invasive interventions and improved quality of life. With the advent of biliary drainage via endoscopic ultrasound (EUS) guidance, EUS guided biliary drainage has been used more frequently within the last decade in different countries. As with any novel advanced endoscopic procedure that encompasses various approaches, advanced endoscopists all over the world have innovated and adopted diverse EUS guided biliary and pancreatic drainage techniques. This diversity has resulted in variations and improvements in EUS Guided biliary and pancreatic drainage; and over the years has led to an extensive nomenclature. The diversity of techniques, nomenclature and recent progress in our intrumentation has led to a dedicated meeting on May 7(th), 2011 during Digestive Disease Week 2011. More than 40 advanced endoscopists from United States, Brazil, Mexico, Venezuela, Colombia, Italy, France, Austria, Germany, Spain, Japan, China, South Korea and India attended this pivotal meeting. The meeting covered improved EUS guided biliary access and drainage procedures, terminology, nomenclature, training and credentialing; as well as emerging devices for EUS guided biliary drainage. This paper summarizes the meeting's agenda and the conclusions generated by the creation of this consortium group.

MR assessment of bile duct size in healthy individuals: comparison with US measurements.

The purpose of the study was to determine the difference in extrahepatic bile duct (EBD) size measured by magnetic resonance (MR) compared with those measured by ultrasound (US). Changes of EBD size related to aging were analyzed too. Size of EBD was measured in 76 randomly selected healthy individuals. Three radiologists blinded to the result of other study preformed measurements by US and three different T2 weighted MR sequences. Correlation and linear regression analysis of obtained data were performed. The mean diameter of EBD measured by US was 3.17 mm and by MR was 3.14 mm on thick slab rapid acquisition with relaxation enhancement (TSE), 3.26 mm on thin section single-shot TSE (HASTE) and 3.30 mm on coronal fully rewound gradient echo (True FISP). There was no statistical difference between US and different MR sequences (p < 0.05). A trend of increase of EBD with age (0.0155 mm per year, p = 0.0954) was observed. Size of EBD highly correlated for each MR sequence with US measurement validating use of MR as a reliable method for evaluation of EBD size. This conclusion is stressed by increase of EBD size with age demonstrated by all measuring methods.

Assessment of biliary bicarbonate secretion in humans by positron emission tomography.

BACKGROUND & AIMS: Positron emission tomography (PET) allows imaging and quantitative analysis of organ functions in basal and stimulated conditions. We have applied this method to the study of biliary bicarbonate secretion in humans. METHODS: PET was performed in 5 healthy subjects and 13 patients with hepatobiliary disorders after intravenous injection of NaH11CO3. In each case the study was performed in basal conditions and after secretin stimulation. Positron emission from the hepatic area was scanned, and normalized uptake values for parenchymal and hilar regions were estimated. RESULTS: In healthy individuals, the injection of NaH11CO3 resulted in a peak uptake of the label in parenchymal and hilar regions 2-3 minutes after the injection. In both normal and cirrhotic subjects, secretin administration increased bicarbonate uptake in the parenchymal region, followed by accumulation of the label in the perihilar area. Normal basal uptake with absent response to secretin was registered in extrahepatic biliary obstruction and in untreated primary biliary cirrhosis (PBC). The secretin response was present in patients with PBC undergoing treatment with ursodeoxycholic acid. CONCLUSIONS: PET allows investigation of biliary bicarbonate secretion in humans. An impaired response to secretin was observed in cholestatic conditions. Preliminary data suggest that ursodeoxycholic acid might improve the response to secretin in PBC.