Normal morphometry of the biliary tree in pediatric and adult populations: A systematic review and meta-analysis.

PURPOSE: This study aimed to characterise the normal morphometry of the biliary tree in pediatric and adult populations, through a systematic review and meta-analysis. METHODS: This study, conducted using the PRISMA guidelines and registered with PROSPERO, searched MEDLINE, EMBASE, SCOPUS and Web of Science databases up to October 2022, and updated to August 2023. Studies that reported extractable data on diameter and length of the right, left and common hepatic ducts (LHD, RHD and CHD), and common bile duct (CBD) were included. Quality of the included studies were assessed using the Anatomical Quality Assessment (AQUA) tool. Statistical analysis included subgroup analyses according to sex, age, geographical location, and imaging modality. RESULTS: In total, 60 studies were included, of which 44 studies reported adequate data for meta-analysis on 23,796 subjects. Overall, the pooled mean diameter of the CBD was 4.69 mm (95 % CI: 4.28-5.11). Significant differences were found between pediatric (1.32 mm, 95 % CI: 1.03-1.61) and adult (4.97 mm, 95 % CI: 4.67-5.27) subjects, as well as US (3.82 mm, 95 % CI: 3.15-4.49) and other imaging modalities, including MRI (6.21 mm, 95 % CI: 4.85-7.57) and ERCP (7.24 mm, 95 % CI: 6.08-8.40). The CBD diameter measured significantly larger distally (5.20 mm, 95 % CI: 4.60-5.80) than proximally (4.01 mm, 95 % CI: 3.51-4.51). CONCLUSIONS: The results obtained from this evidence-based study may guide the establishment of standardised reference values and ranges of the normal biliary tree in pediatric and adult populations and aid clinical understanding.

Spatial architecture of biliary tree in mammals: Fractal and Euclidean geometric features.

The study of the fractal architecture of various organs and structures expanded the possibilities for determining the ranges of their functioning and structural arrangement, which, as a result, was reflected in the development of new approaches to diagnostics and therapeutic impacts. The architecture of the excretory duct systems, similar to the hemo- and lymph- circulatory beds and the bronchial tree, is considered fractal. At the same time, information about hitherto unknown structures of the biliary tree continues to appear in the literature. We aimed to study the features of the spatial geometry of the biliary tree and assess the significance of both its fractal and Euclidean characteristics for the development of approaches that facilitate comprehensive description of intrahepatic biliary tract architecture. We investigated the architecture of the biliary trees of six men, seven male canines, and seven male Wistar rats using the corrosion casting method. Corrosion casts were prepared by injecting solidifying latexes into the bile ducts. The preparations were studied using a light stereomicroscope and a scanning electron microscope. Biliary tree branching is of various types. In addition, the correlation between variations in the caliber and length of the bile ducts and their order is not significant. Therefore, the biliary tree should not be considered as a classical fractal and it consists of the main modules, represented by the network of the bile canaliculi (first nonfractal module) and a biliary tree with a fractal branching (second module) that drains the bile canaliculi mesh and the additional modules represented by the mucosal biliary glands (in mammals with the gallbladder) or the periportal biliary plexus (in mammals without a gallbladder) and the aberrant biliary ducts. Such a configuration of the biliary bed should optimally ensure the smooth implementation of the physiological function of the liver, as well as its adaptation to different pathologies accompanied by biliary hypertension. It also might be considered in the diagnosis and assessment of ductular reaction, biliary regeneration, and/or carcinogenesis.

Bile formation and secretion: An update.

Bile formation is a fundamental physiological process that is vital to the survival of all vertebrates. However, little was known about the mechanisms of this secretion until after World War II. Initial studies involved classic physiologic studies in animal models and humans, which progressed to include studies in isolated cells and membrane vesicles. The advent of molecular biology then led to the identification of specific transport systems that are the determinants of this secretion. Progress in this field was reviewed in the American Physiologic Society's series on "Comprehensive Physiology" in 2013. Herein, we provide an in-depth update of progress since that time.

Producing three-dimensional printed models of the hepatobiliary system from computed tomography imaging data.

INTRODUCTION: Macroscopic anatomy has traditionally been taught using cadaveric material, lectures and a variety of additional resources including online modules and anatomical models. Traditional plastic models are effective educational tools yet they have significant drawbacks such as a lack of anatomical detail, a lack of texturisation and cost. Three-dimensional printed models stand to solve these problems and widen access to high-quality anatomical teaching. This paper outlines the use of three-dimensional multiplanar imaging (computed tomography) in the development of an accurate model of the hepatobiliary system. MATERIALS AND METHODS: Computed tomography scans were used to construct a virtual three-dimensional model of the hepatobiliary system. This was printed locally as a full-size colour model. We give a complete account of the process and software used. DISCUSSION: This study is among the first of a series in which we will document the newly formed Oxford Library of Anatomy. This series will provide the methodology for the production of three-dimensional models from computed tomography and magnetic resonance imaging scans, and the library will provide a complete collection of the most complex anatomical areas. We hope that these models will form an important adjunct in teaching anatomy to medical students and surgical trainees.

Core Hippo pathway components act as a brake on Yap and Taz in the development and maintenance of the biliary network.

The development of the biliary system is a complex yet poorly understood process, with relevance to multiple diseases, including biliary atresia, choledochal cysts and gallbladder agenesis. We present here a crucial role for Hippo-Yap/Taz signaling in this context. Analysis of sav1 mutant zebrafish revealed dysplastic morphology and expansion of both intrahepatic and extrahepatic biliary cells, and ultimately larval lethality. Biliary dysgenesis, but not larval lethality, is driven primarily by Yap signaling. Re-expression of Sav1 protein in sav1-/- hepatocytes is able to overcome these initial deficits and allows sav1-/- fish to survive, suggesting cell non-autonomous signaling from hepatocytes. Examination of sav1-/- rescued adults reveals loss of gallbladder and formation of dysplastic cell masses expressing biliary markers, suggesting roles for Hippo signaling in extrahepatic biliary carcinomas. Deletion of stk3 revealed that the phenotypes observed in sav1 mutant fish function primarily through canonical Hippo signaling and supports a role for phosphatase PP2A, but also suggests Sav1 has functions in addition to facilitating Stk3 activity. Overall, this study defines a role for Hippo-Yap signaling in the maintenance of both intra- and extrahepatic biliary ducts.

Ultrasound findings in paediatric cholestasis: how to image the patient and what to look for.

Paediatric biliary tract and gallbladder diseases include a variety of entities with a wide range of clinical presentations. Cholestasis represents an impaired secretion of bilirubin by hepatocytes, manifesting with high blood levels of conjugated bilirubin and jaundice. Various causes may be involved, which can be recognised analysing blood tests and hepatobiliary imaging, while sometimes liver biopsy or surgery may be necessary. High-resolution real-time ultrasonography is an important tool for differentiation of obstructive and non-obstructive causes of jaundice in infants and children. In this paper, we briefly review the normal anatomy and the ultrasound aspects of main pathologies affecting gallbladder and biliary tree in neonatal and paediatric age.

Clinical usefulness of gadoxetic acid-enhanced MRI for evaluating biliary anatomy in living donor liver transplantation.

OBJECTIVES: To determine the incremental value of hepatobiliary-phase-MRC (HBP-MRC) added to T2-magnetic resonance cholangiography (T2-MRC) for evaluating biliary anatomy in living donor liver transplantation (LDLT) and to correlate T2+HBP-MRC findings with surgical results. METHODS: A total of 276 donors who underwent T2 and gadoxetic acid-enhanced MRI before right hemihepatectomy for LDLT between January and December 2016 were retrospectively enrolled. Two reviewers evaluated biliary anatomy classification using T2-MRC in the first session and T2+HBP-MRC in the second session. The sensitivity, specificity, and confidence level (5-point scale) of T2-MRC and T2+HBP-MRC for variant biliary anatomy were evaluated. The agreement rates between MRC and operative cholangiography for each biliary anatomy classification and the underestimation rates for multiple bile duct openings (BDOs) for both MRC techniques were evaluated. RESULTS: Of the 276 donors, variant biliary anatomy was observed in 36.2% (100/276). T2+HBP-MRC showed a significantly higher sensitivity for diagnosing variant biliary anatomy than T2-MRC alone (99.0% [99/100] vs. 89.0% [89/100], p = 0.006), with better observer confidence level (4.9 ± 0.3 vs. 4.6 ± 0.7, p < 0.001) and inter-observer agreement (kappa, 0.902 vs. 0.730). Compared with T2-MRC alone, T2+HBP-MRC provided significantly higher agreement with operative cholangiography in biliary anatomy classification (98.6% [272/276] vs. 89.9% [248/276], p < 0.001), and significantly lower underestimation rate for multiple BDOs (5.8% [16/276] vs. 9.4% [26/276], p = 0.002). CONCLUSION: T2+HBP-MRC might be considered than T2-MRC alone, as a better depiction of biliary anatomic variations, correlated with surgical findings. KEY POINTS: •T2+HBP-MRC predicted variant biliary anatomy more accurately than T2-MRC alone. •T2+HBP-MRC might have clinical usefulness by reducing the underestimation rate of multiple bile duct openings, which requires more complicated biliary anastomoses.

Magnetic resonance and retrograde endoscopic cholangiopancreatography-based identification of biliary tree variants: are there type-related variabilities among the Saudi population?

PURPOSE: This study investigated biliary tree patterns in a Saudi Arabian population to identify common anatomical variations to establish a common ground for improved surgical practice and to avoid unexpected complications. We consider this type of investigation clinically important because the findings are valuable for pre-surgical planning in a broad range of procedures, including laparoscopic cholecystectomy and liver transplantation. METHODS: We conducted an imaging-based retrospective cross-sectional study involving 150 patients who underwent endoscopic retrograde cholangiopancreatography and magnetic resonance cholangiopancreatography for different indications at King Fahd Hospital of the University between January 2011 and December 2014. RESULTS: Typical right hepatic duct (RHD) tributaries were observed in 56% of patients and typical left hepatic duct (LHD) anatomy was detected in 81.4% of patients. The typical anatomical pattern for the cystic duct was found in 72% of patients. CONCLUSIONS: Our findings showed that types A1 and A3b were the two most common variations in the RHD, whereas those in LHD were types B1 (segment IV duct opens to the LHD), and B2 (segment IV duct opens to the common hepatic duct separately). Although the angular type was the most prevalent among cystic duct variations, there were many differences in the types of variations observed. The findings somewhat correlated with those of other studies, suggesting that the normal biliary tree anatomy is similar among the Saudi population and in other ethnic groups.

Utility of a routine bench cholangiogram for ex situ split liver procedure.

BACKGROUND: Biliary complications can result in a significant morbidity for split liver graft recipients. Biliary drainage for segment 1 and 4 is highly variable and could be the source of bile leaks. Use of a bench cholangiogram (BCH) can accurately define the segmental biliary system and identify any significant biliary radicles that need retention or repair during bench preparation of split grafts. This study evaluates the clinical relevance of routine BCH in split liver transplantation (SLT). METHODS: Retrospective review of 100 BCH images performed during ex situ deceased donor SLT between January 2009 and January 2015. The radiographs were reviewed by two surgeons and the biliary anatomy was compared using Huang and Reichert classification. RESULTS: 100 BCH images were reviewed. Variant anatomy was frequently identified in the intrahepatic bile duct system, the number and drainage patterns of segment 1&4 duct was diverse. BCH results guided the line of parenchymal transection to obtain a single segment 2&3 duct in 15 cases. A surgical intervention in the form of suture ligation of significant segment 1 or 4 duct at bench preparation was performed in 6 cases. BCH images guided surgical control of post-operative bile leak in 3 patients. CONCLUSION: Bench cholangiogram is a useful tool to guide liver parenchymal transection and potentially reduce the incidence of biliary complications.

Embryology, Anatomy, and Imaging of the Biliary Tree.

"The anatomy of the biliary tree is notoriously variable. This variation is the bane of the hepatobiliary surgeon, to whom an understanding of biliary anatomic variation is key to the planning and safe conduct of liver surgery, from oncological resections to split-liver transplantation. The hepatic diverticulum, also termed "the liver bud," is the first semblance of the biliary system in the human embryo. A variety of techniques used in the mid twentieth century for imaging the biliary tree have since been abandoned in favor of more practical, safer, less invasive, and more sensitive and specific contemporary methods."

Reference limits for hepatic bile duct-to-arteriole and bile duct-to-portal tract ratios in healthy cats.

OBJECTIVE To establish reference limits for hepatic bile duct-to-arteriole ratio (BD:A) and bile duct-to-portal tract ratio (BD:PT) in healthy cats and assess whether these parameters could be used to support a diagnosis of biliary ductopenia in cats. SAMPLE Hepatic biopsy samples from healthy cats (n = 20) and cats with ductopenia (2). PROCEDURES Hepatic biopsy samples from healthy cats were used to count the number of bile ducts and hepatic arterioles in 20 portal tracts for each cat. Mean BD:A and mean BD:PT for each cat were calculated, and these values were used to determine reference limits for mean BD:A and mean BD:PT. Results of histologic evaluation, including immunohistochemical staining in some instances, were compared for healthy cats versus cats with ductopenia. RESULTS Of the 400 portal tracts from healthy cats, 382 (95.5%) and 396 (99.0%) had BD:A and BD:PT, respectively, ≥ 1.0, with less variability in BD:A. Mean BD:A and BD:PT were markedly lower in both cats with ductopenia, compared with values for healthy cats. However, only mean BD:A for cats with ductopenia was below the reference limit of 0.59. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that systematic evaluation of BD:A, with a lower reference limit of 0.59 to define biliary ductopenia in cats, may be a discrete and easily applied morphometric tool to enhance detection of ductopenia in cats. However, application of this ratio required evaluation of ≥ 20 portal tracts with cross-sectioned portal elements to determine a mean BD:A value.

Clinical Feasibility of Gadoxetic Acid-Enhanced Isotropic High-Resolution 3-Dimensional Magnetic Resonance Cholangiography Using an Iterative Denoising Algorithm for Evaluation of the Biliary Anatomy of Living Liver Donors.

OBJECTIVES: The aim of this study was to evaluate the clinical feasibility of gadoxetic acid-enhanced isotropic high-resolution (IHR) 3-dimensional (3D) T1-weighted (T1W) magnetic resonance cholangiography (MRC) using an iterative denoising (ID) algorithm for evaluation of the biliary anatomy of living liver donors in comparison with conventional 3D multislice T2-weighted (T2W) MRC. MATERIALS AND METHODS: In this institutional review board-approved retrospective study, a total of 75 living liver donors who underwent conventional 3D multislice T2W-MRC and IHR-3D-T1W-MRC on a 3 T scanner and subsequent right hepatectomy for liver donation were included. Isotropic high-resolution T1W-MRCs were obtained in both axial and coronal planes using the 3D VIBE Dixon sequence and an ID algorithm implemented with wavelet thresholding of 3D complex-valued data of the noise level, g-factor, and k-space filtering. Thereafter, 3 board-certified radiologists independently reviewed the examinations for visibility and sharpness of the bile ducts (BDs), as well as overall image quality on a 5-point scale. For diagnostic performance, anatomic variations of the BD, length of right hepatic duct, and the expected number of BD openings at right hepatectomy were also recorded. As the reference standard, BD variation was determined by surgeons in consensus using intraoperative real-time fluorescent cholangiography. RESULTS: Mean acquisition times of 3D-T2W-MRC and IHR-T1W-MRC were 367 seconds and 17 seconds (P < 0.001), respectively. Compared with 3D-T2W-MRCs, IHR-T1W-MRCs yielded significantly improved visibility and sharpness of all evaluated intrahepatic bile ducts (all Ps < 0.05), and higher overall image quality (P < 0.01). The IHR-T1W-MRCs also demonstrated significantly higher agreement in BD variation (87.6% vs 81.3%, P = 0.03) and expected BD openings (76.9% vs 70.2%, P = 0.006) than 3D-T2W-MRC compared with the reference standard. Interobserver agreement in estimating the length of right hepatic duct, IHR-T1W-MRC showed excellent interobserver agreement (intraclass correlation coefficient, 0.94), whereas 3D-T2W-MRC showed good interobserver agreement (intraclass correlation coefficient, 0.78). CONCLUSIONS: Isotropic high-resolution T1W-MRCs with ID provided significantly improved BD image quality and more accurate depiction of the BD anatomy and BD openings at right donor hemihepatetomy than 3D-T2W-MRC.

High spatial resolution navigated 3D T1-weighted hepatobiliary MR cholangiography using Gd-EOB-DTPA for evaluation of biliary anatomy in living liver donors.

PURPOSE: To determine the feasibility of high-resolution navigated three-dimensional (3D) T1-weighted hepatobiliary MR cholangiography (Nav T1 MRC) using Gd-EOB-DTPA for biliary visualization in living liver donors and to assess added value of 3D T1-weighted hepatobiliary MRCs in improving the confidence and diagnostic accuracy of biliary anatomy in complementary to T2-weighted MRCs. METHODS: Twenty-nine right liver donors underwent 3D T2 MRC, 2D T2 MRC, breath-hold T1-weighted hepatobiliary MRC (BH T1 MRC), and Nav T1 MRC. Two readers independently reviewed and compared 3D/2D MRC set, added BH T1 MRC set, and added Nav T1 MRC set for biliary diagnostic accuracy and confidence. For each MRC, biliary segments visualization and image quality were scored. RESULTS: Both BH T1 MRC and Nav T1 MRC improved accuracy and specificity in biliary diagnosis when added to 3D/2D T2 MRC-alone set, though without statistical significance (R1, 82.8% to 93.1%; R2, 82.8% to 89.7%). The added Nav T1 MRC set showed the highest diagnostic confidence with both readers. Both readers scored Nav T1 MRC with the highest visualization scores for branching ducts and overall ducts. CONCLUSION: Combining T1-weighted hepatobiliary MRCs to 3D/2D T2 MRC set improved accuracy for biliary anatomy diagnosis; time-efficient BH T1 MRC in axial and coronal planes should be considered as a key MRC sequence complementary to T2 MRCs. Given excellent biliary visualization and superior diagnostic confidence, Nav T1 MRC in selected subjects with breath-hold difficulties and inconclusive or complex biliary variations may assist in reaching a correct biliary diagnosis.

Using a Whole-mount Immunohistochemical Method to Study the Innervation of the Biliary Tract in Suncus murinus.

This work describes the whole-mount immunohistochemistry staining method in detail, using neurofilament protein antibody to label the innervation of the biliary tract in Suncus murinus (S. murinus ). First, the specimen was dissected from S. murinus and fixed in 4% paraformaldehyde (PFA). Second, an enzymatic treatment and potential endogenous peroxidase inactivation were performed. The specimen was then exposed to the primary antibody, anti-neurofilament protein antibody, for 3-6 days. It was then incubated with the secondary antibody conjugated with horseradish peroxidase. The color reaction was revealed by reacting the specimen with a 3,3'-diaminobenzidine (DAB) substrate. This method can be applied to analyze the innervation of all visceral organs. Furthermore, this protocol can also be adapted to test other neuronal antibodies, but optimization of the antibodies should be done first. This method was originally introduced by Kuratani and Tanaka1,2,3.

Anomalous biliary and vascular anatomy-Potential pitfalls during cholecystectomy.

Laparoscopic cholecystectomy is usually a low-risk procedure associated with a short stay and a low rate of conversion to open surgery. Complications are sometimes associated with anomalous vascular or biliary anatomy. Outlined below are the variations in vascular and biliary anatomy which may result in complications either due to involvement in the inflammatory process or inadvertent division during dissection. Clin. Anat. 30:1103-1106, 2017. © 2017 Wiley Periodicals, Inc.

MR cholangiography in potential liver donors: quantitative and qualitative improvement with administration of an oral effervescent agent.

PURPOSE: To determine whether an oral effervescent agent improves magnetic resonance cholangiography (MRC) images, both qualitatively and quantitatively, in potential live liver donors. MATERIALS AND METHODS: This retrospective study was approved by the Institutional Review Board, and informed consent was waived. Seventy potential liver donors underwent 2D MRC before and after administration of an oral effervescent agent. One radiologist measured relative contrast ratio (rC) and relative signal intensity (rS) for right and left intrahepatic ducts (RHD and LHD), and common hepatic duct (CHD). After assessment of overall image quality, two other radiologists independently scored visualization of five ductal segments (RHD, LHD, CHD, cystic, and common bile duct) and assessed the preferred image set. In consensus, they assessed the biliary anatomy. The data were analyzed using a paired t-test, Wilcoxon's signed-rank test, and chi-square test. RESULTS: Both rC and rS of RHD and CHD were significantly higher on MRC images after administration of an oral effervescent agent than before (P < 0.03). The overall image quality grades and biliary visualization scores for all five duct segments were significantly higher on MRC images after administration of an oral effervescent agent than before (P < 0.0001). Between these images, both readers more often preferred MRC images with an effervescent agent rather than those without this agent (reader 1: 56/70, 80.0%; reader 2: 55/70, 78.6%; P = 0.0003). The readers correctly assessed second-order biliary tract anatomy in two more subjects on MRC after administration of an effervescent agent than before. CONCLUSION: Oral administration of an effervescent agent improves MRC images, both qualitatively and quantitatively, in live liver donors. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1656-1663.