The unique capacity, robust vascular supply, and drainage of the liver allow for surgeons to perform formal, nonanatomic, and parenchymal sparing resections for primary and metastatic hepatic lesions. Knowledge of hepatobiliary anatomy is crucial to allow for safe dissection and adequate preservation of the future liver remnant. The functional anatomy of the liver is based on Couinaud classification. Vascular, portal and biliary anatomic variations are necessary to identify on preoperative imaging to avoid unintentional injuries. Conventional common hepatic artery, hepatic arterial branches, portal, and biliary anatomy account for 89%, 55%, 92.5%, and 57%, respectively, of the population.Copyright © 2024 Elsevier Inc. All rights reserved.

In recent years, with a deeper understanding of pathologic changes in hepatolithiasis, more and more attention has been paid to the relationship of postoperative remnant proliferative cholangitis (PC) with stone recurrence and biliary restenosis, but effective management strategies have not yet been developed. Thus, the aim of this study was to determine whether epidermal growth factor receptor inhibitor (AG-1478) could inhibit hyperplasia and lithogenic potentiality of PC.The PC animal model was established via retrograde insertion of a 5-0 nylon thread into the common bile duct through Vater's papilla. The common bile duct in the therapeutic group received a single intraluminal administration of AG-1478, followed by weekly intraperitoneal injections of AG-1478. Subsequently, influence of EGFR inhibitor on hyperplasia, apoptosis, and lithogenic potential of PC were evaluated via histology, expression changes of EGFR, BrdU, Ki-67, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), Fas, mucin 5 AC, and collagen I.EGFR inhibitor AG-1478 was effective not only in inhibiting the mRNA and protein expression of EGFR, BrdU, and Ki-67, but also in increasing Fas mRNA expression and TUNEL-positive cells, as a result leading to the inhibition of hyperplasia of the biliary epithelium, submucosal gland, and collagen fibers in the diseased bile duct. Additionally, collagen I expression and fibrous thickness of the bile duct wall was significantly reduced, thereby reducing the incidence of biliary tract stricture secondary to PC. Also of note, treatment with AG-1478 could efficiently decrease the lithogenic potential of PC via inhibition of mucin 5AC expression and mucoglycoprotein secretion, hereby facilitating prevention of stone recurrence.EGFR antagonist AG-1478 had a potent anti-proliferative and anti-fibrotic effectiveness on PC and, therefore, holds promise as a candidate of PC treatment.Copyright © 2011 Elsevier Inc. All rights reserved.

The mechanics of bile flow in the biliary system plays an important role in studying bile stasis and gallstone formation. Bile duct stricture is an abnormal phenomenon that refers to the bile duct getting smaller or narrower. The main objective of this study is to study the influence of stricture on bile flow dynamics using numerical methods. We employed a numerical Computational Fluid Dynamics model of the bile flow within a strictured hepatic duct. We studied and compared the influence of stricture severity, stricture length, eccentricity, and bile flow property on the bile flow dynamics. The bile flow velocity, pressure distribution, pressure drop, and wall shear stress are provided in detail. The stricture alters the normal bile flow pattern and increases flow resistance. At the location upstream and downstream of the stricture, bile flow slows down. In the area of the stricture throat, bile flow is accelerated, and recirculation forms behind the stricture. The maximum pressure drop of the biliary system increases with the stricture length. The eccentricity makes the flow deflect away from the duct's centerline. The behavior of the deflected flow is significantly altered downstream of the stricture. Such bile flow behavior as deceleration and recirculation may lead to cholestasis. Stricture alters bile flow in the biliary tract, causing changes in biliary hydrodynamic indexes, which could potentially serve as an omen for gallstone formation and other related diseases. The consideration of the bile duct stricture could lead to better patient stratification.

The extracellular matrix is a highly reactive scaffold formed by a wide array of multifunctional molecules, encompassing collagens and noncollagenous glycoproteins, proteoglycans, glycosaminoglycans, and polysaccharides. Besides outlining the tissue borders, the extracellular matrix profoundly regulates the behavior of resident cells by transducing mechanical signals, and by integrating multiple cues derived from the microenvironment. Evidence is mounting that changes in the biostructure of the extracellular matrix are instrumental for biliary repair. Following biliary damage and eventually, malignant transformation, the extracellular matrix undergoes several quantitative and qualitative modifications, which direct interactions among hepatic progenitor cells, reactive ductular cells, activated myofibroblasts and macrophages, to generate the ductular reaction. Herein, we will give an overview of the main molecular factors contributing to extracellular matrix remodeling in cholangiopathies. Then, we will discuss the structural alterations in terms of biochemical composition and physical stiffness featuring the “desmoplastic matrix” of cholangiocarcinoma along with their pro-oncogenic effects.

The biliary system consists of intrahepatic and extrahepatic bile ducts lined by biliary epithelial cells (cholangiocytes). Bile ducts and cholangiocytes are affected by a variety of disorders called cholangiopathies, which differ in aetiology, pathogenesis, and morphology. Classification of cholangiopathies is complex and reflects pathogenic mechanisms (immune-mediated, genetic, drug- and toxin-induced, ischaemic, infectious, neoplastic), predominant morphological patterns of biliary injury (suppurative and non-suppurative cholangitis, cholangiopathy), and specific segments of the biliary tree affected by the disease process. While the involvement of large extrahepatic and intrahepatic bile ducts is typically visualised using radiology imaging, histopathological examination of liver tissue obtained by percutaneous liver biopsy still plays an important role in the diagnosis of cholangiopathies affecting the small intrahepatic bile ducts. To increase the diagnostic yield of a liver biopsy and determine the optimal therapeutic approach, the referring clinician is tasked with interpreting the results of histopathological examination. This requires knowledge and understanding of basic morphological patterns of hepatobiliary injury and an ability to correlate microscopic findings with results obtained by imaging and laboratory methods. This minireview describes the morphological aspects of small-duct cholangiopathies pertaining to the diagnostic process.©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.

Gallstones grow inside the gallbladder or biliary tract. These stones can be asymptomatic or symptomatic; only gallstones with symptoms or complications are defined as gallstone disease. Based on their composition, gallstones are classified into cholesterol gallstones, which represent the predominant entity, and bilirubin ('pigment') stones. Black pigment stones can be caused by chronic haemolysis; brown pigment stones typically develop in obstructed and infected bile ducts. For treatment, localization of the gallstones in the biliary tract is more relevant than composition. Overall, up to 20% of adults develop gallstones and >20% of those develop symptoms or complications. Risk factors for gallstones are female sex, age, pregnancy, physical inactivity, obesity and overnutrition. Factors involved in metabolic syndrome increase the risk of developing gallstones and form the basis of primary prevention by lifestyle changes. Common mutations in the hepatic cholesterol transporter ABCG8 confer most of the genetic risk of developing gallstones, which accounts for similar to 25% of the total risk. Diagnosis is mainly based on clinical symptoms, abdominal ultrasonography and liver biochemistry tests. Symptoms often precede the onset of the three common and potentially life-threatening complications of gallstones (acute cholecystitis, acute cholangitis and biliary pancreatitis). Although our knowledge on the genetics and pathophysiology of gallstones has expanded recently, current treatment algorithms remain predominantly invasive and are based on surgery. Hence, our future efforts should focus on novel preventive strategies to overcome the onset of gallstones in at-risk patients in particular, but also in the population in general.

Pigment stones are thought to form as a result of deconjugation of bilirubin by bacterial beta-glucuronidase, which results in precipitation of calcium bilirubinate. Calcium bilirubinate is then aggregated into stones by an anionic glycoprotein. Slime (glycocalyx), an anionic glycoprotein produced by bacteria causing foreign body infections, has been implicated in the formation of the precipitate that blocks biliary stents. We previously showed that bacteria are present within the pigment portions of gallstones and postulated a bacterial role in pigment stone formation through beta-glucuronidase or slime production. Ninety-one biliary bacterial isolates from 61 patients and 12 control stool organisms were tested for their production of beta-glucuronidase and slime. The average slime production was 42 for biliary bacteria and 2.5 for stool bacteria (P <0.001). Overall, 73% of biliary bacteria and 8% of stool bacteria produced slime (optical density >3). In contrast, only 38% of biliary bacteria produced beta-glucuronidase. Eighty-two percent of all patients, 90% of patients with common bile duct (CBD) stones, 100% of patients with primary CBD stones, and 93% of patients with biliary tubes had one or more bacterial species in their stones that produced slime. By comparison, only 47% of all patients, 60% of patients with CBD stones, 62% of patients with primary CBD stones, and 50% of patients with biliary tubes had one or more bacteria that produced beta-glucuronidase. Most biliary bacteria produced slime, and slime production correlated better than beta-glucuronidase production did with stone formation and the presence of biliary tubes or stents. Patients with primary CBD stones and biliary tubes had the highest incidence of slime production. These findings suggest that bacterial slime is important in gallstone formation and the blockage of biliary tubes.

The solubility of cholesterol in bile salt (BS) micelles is important to understand the availability of cholesterol for absorption in the intestinal epithelium and to develop strategies to decrease cholesterol intake from the intestinal lumen. This has been the subject of intense investigation, due to the established relation between the development of diseases such as atherosclerosis and high levels of cholesterol in the blood. In this work we quantify the effect of BS variability on the amount of cholesterol solubilized. The effect of some known hypocholesterolemic agents usually found in the diet is also evaluated, as well as some insight regarding the mechanisms involved. The results show that, depending on the bile salt composition, the average value of sterol per micelle is equal to or lower than 1. The amount of cholesterol solubilized in the BS micelles is essentially equal to its total concentration until the solubility limit is reached. Altogether, this indicates that the maximum cholesterol solubility in the BS micellar solution is the result of saturation of the aqueous phase and depends on the partition coefficient of cholesterol between the aqueous phase and the micellar pseudophase. The effect on cholesterol maximum solubility for several food ingredients usually encountered in the diet was characterized using methodology developed recently by us. This method allows the simultaneous quantification of both cholesterol and food ingredient solubilized in the BS micelles even in the presence of larger aggregates, therefore avoiding their physical separation with possible impacts on the overall equilibrium. The phytosterols stigmasterol and stigmastanol significantly decreased cholesterol solubility with a concomitant reduction in the total amount of sterol solubilized, most pronounced for stigmasterol. Those results point toward coprecipitation being the major cause for the decrease in cholesterol solubilization by the BS micelles. The presence of tocopherol and oleic acid leads to a small decrease in the amount of cholesterol solubilized while palmitic acid slightly increases the solubility of cholesterol. Those dietary food ingredients are completely solubilized by the BS micelles, indicating that the effects on cholesterol solubility are due to changes in the properties of the mixed micelles.

Bile is a unique and vital aqueous secretion of the liver that is formed by the hepatocyte and modified down stream by absorptive and secretory properties of the bile duct epithelium. Approximately 5% of bile consists of organic and inorganic solutes of considerable complexity. The bile-secretory unit consists of a canalicular network which is formed by the apical membrane of adjacent hepatocytes and sealed by tight junctions. The bile canaliculi (∼1 μm in diameter) conduct the flow of bile countercurrent to the direction of portal blood flow and connect with the canal of Hering and bile ducts which progressively increase in diameter and complexity prior to the entry of bile into the gallbladder, common bile duct, and intestine. Canalicular bile secretion is determined by both bile salt-dependent and independent transport systems which are localized at the apical membrane of the hepatocyte and largely consist of a series of adenosine triphosphate-binding cassette transport proteins that function as export pumps for bile salts and other organic solutes. These transporters create osmotic gradients within the bile canalicular lumen that provide the driving force for movement of fluid into the lumen via aquaporins. Species vary with respect to the relative amounts of bile salt-dependent and independent canalicular flow and cholangiocyte secretion which is highly regulated by hormones, second messengers, and signal transduction pathways. Most determinants of bile secretion are now characterized at the molecular level in animal models and in man. Genetic mutations serve to illuminate many of their functions.© 2013 American Physiological Society.

The cellular microenvironment plays an integral role in improving the function of microengineered tissues. Control of the microarchitecture in engineered tissues can be achieved through photopatterning of cell-laden hydrogels. However, despite high pattern fidelity of photopolymerizable hydrogels, many such materials are not cell-responsive and have limited biodegradability. Here, we demonstrate gelatin methacrylate (GelMA) as an inexpensive, cell-responsive hydrogel platform for creating cell-laden microtissues and microfluidic devices. Cells readily bound to, proliferated, elongated, and migrated both when seeded on micropatterned GelMA substrates as well as when encapsulated in microfabricated GelMA hydrogels. The hydration and mechanical properties of GelMA were demonstrated to be tunable for various applications through modification of the methacrylation degree and gel concentration. The pattern fidelity and resolution of GelMA were high and it could be patterned to create perfusable microfluidic channels. Furthermore, GelMA micropatterns could be used to create cellular micropatterns for in vitro cell studies or 3D microtissue fabrication. These data suggest that GelMA hydrogels could be useful for creating complex, cell-responsive microtissues, such as endothelialized microvasculature, or for other applications that require cell-responsive microengineered hydrogels.Copyright (c) 2010 Elsevier Ltd. All rights reserved.

The clinical outcomes and prevalence of adverse events associated with biliary biodegradable stents (BS) can differ according to degradation process and time. The aim of this study was to observe the degradation process and time of different BS prototypes, and to evaluate sequential changes in their mechanical properties.

A biliary stent is used to expand the bile duct during interventional treatment of biliary stricture. To reduce the complications after stent implantation, it is necessary to understand and improve the comprehensive performance of magnesium alloy biliary stents. In this study, at first, the mechanical performance of magnesium alloy biliary stent in bile ducts with different ellipticitiesis studied, and the influence of the ellipticity of bile duct on the interaction of the stent‐bile duct coupling system is better understood. Proposed results show the increment of ellipticity of the bile duct will increase the difficulty of expanding the stent. Second, to improve the mechanical performance and degradation performance of the stent simultaneously, an optimal design method based on a zero‐order algorithm is used to reduce the maximum equivalent stress on the stent effectively, to make the stress distribution more uniform, and to expand the bile duct of the lesion more effectively and uniformly. The results of this analysis and optimization are useful to predict the clinical effect of stents and to design and optimize stents for both bile duct and other non‐vascular

Benign biliary strictures (BBS) are widely treated by endoscopic procedures involving temporary stent placement. Occasionally, stents are required to be removed, making the treatment process very painful as well as expensive. Until now, no effective biodegradable biliary stents are available for clinical applications. This study aims to investigate the safety and efficacy of biodegradable polydioxanone (PDO) and polylactic acid (PLA) braided biodegradable biliary stents (BDBS) both in vitro and in vivo.Three different diameter monofilaments of PDO (0.30, 0.35, and 0.40 mm) and PLA (0.10, 0.15, and 0.20 mm) were braided to biliary stents and their mechanical properties were studied. The stents were placed in an ex vivo bile duct model perfused with porcine bile, taken out, and observed every week until these were completely degraded. After the bile duct stenosis model was established successfully in piglet, stents with appropriate mechanical properties were further examined under endoscopy; haematology, patency time of stents, and pathological changes were observed for eight months.A total of 10 pigs were included (two groups; 5 PDO, 5 PLA) in the study. The patency time of the PLA group was significantly longer than that of the PDO stent group (25.7 ± 5.6w vs 11.3 ± 3.4w, respectively) in pigs.Our results prospect biodegradable PLA and PDO braided biliary stents could be a better choice to treat benign biliary strictures while degrading at different rates.

Gallbladder cancer can be difficult to detect in its early stages and is prone to metastasize, causing bile duct obstruction, which is usually treated by stent implantation in clinic. However, the commonly used biliary stents are non-degradable, which not only prone to secondary blockage, but also need to be removed by secondary surgery. Biodegradable magnesium (Mg) is expected to one of the promising candidates for degradable biliary stents due to its excellent physicochemical property and biocompatibility. In this work, we studied the influence of high-purity Mg wires on gallbladder cancer through in vitro and in vivo experiments and revealed that the degradation products of Mg could significantly inhibit the growth of gallbladder cancer cells and promote their apoptosis. Our findings indicate that Mg biliary stent possesses the function of draining bile and treating gallbladder cancer, suggesting that Mg has good application prospects in biliary surgery.Copyright © 2021. Published by Elsevier Ltd.