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1.
J Biochem Mol Toxicol ; 38(8): e23788, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39087918

ABSTRACT

In this study, we evaluated the hepatoprotective effects of astaxanthin, a natural carotenoid, against the cholestatic liver fibrosis induced by bile duct ligation (BDL). Toward this end, male rats were subjected to BDL and treated with astaxanthin for 35 days. Afterwards, their serum and liver biochemical factors were assessed. Also, histopathological and immunohistochemical analyses were performed to determine the fibrosis and the expression levels of alpha-smooth muscle actin (α-SMA) and transforming growth factor beta (TGF-ß1) in the liver tissue. Based on the results, BDL caused a significant increase in liver enzyme levels, blood lipids, and bilirubin, while decreasing the activity of superoxide dismutase(SOD), catalase (CAT), and glutathione (GSH) enzymes. Also, in the BDL rats, hepatocyte necrosis, infiltration of inflammatory lymphocytes, and hyperplasia of bile ducts were detected, along with a significant increase in α-SMA and TGF-ß1 expression. Astaxanthin, however, significantly prevented the BDL's detrimental effects. In all, 10 mg/kg of this drug maintained the bilirubin and cholesterol serum levels of BDL rats at normal levels. It also reduced the liver enzymes' activity and serum lipids, while increasing the SOD, CAT, and GSH activity in BDL rats. The expression of α-SMA and TGF-ß1 in the BDL rats treated with 10 mg/kg of astaxanthin was moderate (in 34%-66% of cells) and no considerable cholestatic fibrosis was observed in this group. However, administrating the 20 mg/kg of astaxanthin was not effective in this regard. These findings showed that astaxanthin could considerably protect the liver from cholestatic damage by improving the biochemical features and regulating the expression of related proteins.


Subject(s)
Bile Ducts , Cholestasis , Liver Cirrhosis , Rats, Wistar , Xanthophylls , Animals , Xanthophylls/pharmacology , Xanthophylls/therapeutic use , Male , Rats , Cholestasis/pathology , Cholestasis/metabolism , Cholestasis/drug therapy , Liver Cirrhosis/metabolism , Liver Cirrhosis/pathology , Liver Cirrhosis/drug therapy , Liver Cirrhosis/prevention & control , Ligation , Bile Ducts/surgery , Liver/drug effects , Liver/pathology , Liver/metabolism , Transforming Growth Factor beta1/metabolism
2.
Res Vet Sci ; 176: 105343, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38970869

ABSTRACT

Cholestasis is a hepatic disease reported in humans, dogs, and chickens and is characterized by various signs. Bile duct ligation (BDL) is a standard model for research in cholestasis in male rats and mice. However, the timing and degree of structural changes in BDL-subjected liver differ in the two animal species. This study focused on chickens as a choice model for cholestasis. Specifically, we aimed to evaluate the features of BDL in hens and compare them with those in rats and mice. Eighteen hens, 19 female ICR mice, and 18 female SD rats were randomly divided into the sham-operated and BDL groups. At 2, 4, and 6 weeks after BDL, and 4 weeks after the sham operation, liver and blood samples were collected and analyzed histologically and biochemically. Histologically, bile duct proliferation in BDL-subjected livers was first observed in the chickens and then the rats and mice, whereas CD44-positive small hepatocytes were observed only in chickens in the BDL group. Biochemically, the mRNA expression of the hepatocyte growth factor was higher in BDL-subjected chickens, while Interleukin 6 expression was higher in the BDL-subjected rats and mice than in animals in the sham group. In addition, farnesoid X receptor mRNA expression was lower in the BDL-subjected chickens than in the sham chickens. The BDL group had significantly higher total bile acid blood concentration than the sham group. In conclusion, the signs of hepatopathy caused by BDL differ among animal species. Furthermore, we propose that compared to BDL-subjected mice and rats, BDL-subjected chickens are a novel cholestasis animal model that demonstrates severe hepatopathy and liver restructuring.


Subject(s)
Bile Ducts , Chickens , Cholestasis , Liver , Mice, Inbred ICR , Rats, Sprague-Dawley , Animals , Cholestasis/veterinary , Cholestasis/pathology , Female , Ligation , Bile Ducts/pathology , Bile Ducts/surgery , Rats , Liver/pathology , Mice , Species Specificity , Disease Models, Animal , Poultry Diseases/pathology
3.
PLoS One ; 19(7): e0303786, 2024.
Article in English | MEDLINE | ID: mdl-38950046

ABSTRACT

A prevailing animal model currently used to study severe human diseases like obstructive cholestasis, primary biliary or sclerosing cholangitis, biliary atresia, and acute liver injury is the common bile duct ligation (cBDL). Modifications of this model include ligation of the left hepatic bile duct (pBDL) or ligation of the left bile duct with the corresponding left hepatic artery (pBDL+pAL). Both modifications induce cholestasis only in the left liver lobe. After induction of total or partial cholestasis in mice, the well-being of these animals was evaluated by assessing burrowing behavior, body weight, and a distress score. To compare the pathological features of these animal models, plasma levels of liver enzymes, bile acids, bilirubin, and within the liver tissue, necrosis, fibrosis, inflammation, as well as expression of genes involved in the synthesis or transport of bile acids were assessed. The survival rate of the animals and their well-being was comparable between pBDL+pAL and pBDL. However, surgical intervention by pBDL+pAL caused confluent necrosis and collagen depositions at the edge of necrotic tissue, whereas pBDL caused focal necrosis and fibrosis in between portal areas. Interestingly, pBDL animals had a higher survival rate and their well-being was significantly improved compared to cBDL animals. On day 14 after cBDL liver aspartate, as well as alanine aminotransferase, alkaline phosphatase, glutamate dehydrogenase, bile acids, and bilirubin were significantly elevated, but only glutamate dehydrogenase activity was increased after pBDL. Thus, pBDL may be primarily used to evaluate local features such as inflammation and fibrosis or regulation of genes involved in bile acid synthesis or transport but does not allow to study all systemic features of cholestasis. The pBDL model also has the advantage that fewer mice are needed, because of its high survival rate, and that the well-being of the animals is improved compared to the cBDL animal model.


Subject(s)
Cholestasis , Disease Models, Animal , Liver , Animals , Ligation , Mice , Cholestasis/metabolism , Cholestasis/pathology , Liver/metabolism , Liver/pathology , Bile Ducts/surgery , Bile Ducts/pathology , Bile Ducts/metabolism , Bile Acids and Salts/metabolism , Male , Bilirubin/blood , Bilirubin/metabolism , Mice, Inbred C57BL , Common Bile Duct/surgery
4.
Colloids Surf B Biointerfaces ; 241: 114064, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38954937

ABSTRACT

Bile duct injury presents a significant clinical challenge following hepatobiliary surgery, necessitating advancements in the repair of damaged bile ducts is a persistent issue in biliary surgery. 3D printed tubular scaffolds have emerged as a promising approach for the repair of ductal tissues, yet the development of scaffolds that balance exceptional mechanical properties with biocompatibility remains an ongoing challenge. This study introduces a novel, bio-fabricated bilayer bile duct scaffold using a 3D printing technique. The scaffold comprises an inner layer of polyethylene glycol diacrylate (PEGDA) to provide high mechanical strength, and an outer layer of biocompatible, methacryloylated recombinant collagen type III (rColMA) loaded with basic fibroblast growth factor (bFGF)-encapsulated liposomes (bFGF@Lip). This design enables the controlled release of bFGF, creating an optimal environment for the growth and differentiation of bone marrow mesenchymal stem cells (BMSCs) into cholangiocyte-like cells. These cells are instrumental in the regeneration of bile duct tissues, evidenced by the pronounced expression of cholangiocyte differentiation markers CK19 and CFTR. The PEGDA//rColMA/bFGF@Lip bilayer bile duct scaffold can well simulate the bile duct structure, and the outer rColMA/bFGF@Lip hydrogel can well promote the growth and differentiation of BMSCs into bile duct epithelial cells. In vivo experiments showed that the scaffold did not cause cholestasis in the body. This new in vitro pre-differentiated active 3D printed scaffold provides new ideas for the study of bile duct tissue replacement.


Subject(s)
Bile Ducts , Cell Differentiation , Hydrogels , Mesenchymal Stem Cells , Polyethylene Glycols , Printing, Three-Dimensional , Polyethylene Glycols/chemistry , Hydrogels/chemistry , Hydrogels/pharmacology , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/cytology , Animals , Cell Differentiation/drug effects , Recombinant Proteins/pharmacology , Collagen/chemistry , Tissue Scaffolds/chemistry , Mice , Fibroblast Growth Factor 2/pharmacology , Cells, Cultured , Humans , Male
7.
S Afr J Surg ; 62(2): 70, 2024 May.
Article in English | MEDLINE | ID: mdl-38838126

ABSTRACT

BACKGROUND: Magnetic resonance imaging (MRI) is widely regarded as the gold standard for assessment of the bile ducts in patients with bile duct injuries (BDIs). This case series aims to highlight the shortcomings of this imaging modality and demonstrate how it may overestimate the injury severity. METHODS: Three patients treated at Groote Schuur Hospital and the University of Cape Town in whom MRI/magnetic resonance cholangiopancreatography (MRCP) overestimated the severity of BDI were included in the study. Demographic characteristics, clinical presentation, blood results and imaging findings are presented. RESULTS: All patients had an MRI/MRCP done which assessed the BDIs as major complete cut-off of the proximal common hepatic duct with substance loss. Subsequent direct cholangiography showed minor injuries and all three patients were successfully managed with endoscopic stenting. CONCLUSION: Major BDIs are complex, and assessment of severity is intricate and may be overestimated. These patients are best managed in high-volume multidisciplinary team settings.


Subject(s)
Cholangiopancreatography, Magnetic Resonance , Humans , Male , Adult , Female , Bile Ducts/injuries , Bile Ducts/diagnostic imaging , Middle Aged
8.
J Gastrointestin Liver Dis ; 33(2): 254-260, 2024 Jun 29.
Article in English | MEDLINE | ID: mdl-38944859

ABSTRACT

BACKGROUND AND AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) with brush cytology is an important tool in the diagnosis of hepatobiliary malignancies. However, reported sensitivity of brush cytology is suboptimal and differs markedly per study. The aim of this study is to analyze the optimal technique of endobiliary brushing during ERCP. METHODS: A systematic review and meta-analysis according was performed using Pubmed, Embase and Cochrane library, and reported reported according to the PRISMA guidelines. The intervention reported should involve ERCP, performed by the endoscopist with a comparison of different brushing techniques. The primary outcome was sensitivity for malignancy. Studies published up to December 2022 were included. Percutaneous techniques and cytological or laboratory techniques for processing of material were excluded. Bias was assessed using the Quadas-2 tool. Pooled sensitivity rates and Forest plots were analyzed for the primary outcome. RESULTS: A total of 16 studies were included. Three studies reported on brushing before or after dilation of a biliary stricture. No improvement in sensitivity was found. Five studies reported on alternative brush designs. This did not lead to improved sensitivity. Seven studies reported on the aspiration and analysis of bile fluid, which resulted in a 16% increase in sensitivity (95% CI 4-29%). One study reported an increased in the number of brush passes to the stricture, providing an increase in sensitivity of 20%. Substantial heterogeneity between studies was found, both methodological and statistical. CONCLUSIONS: Increasing the number of brush-passes and sending bile fluid for cytology increases the sensitivity of biliary brushings during ERCP. Dilation before brushing or alternative brush designs did not increase sensitivity.


Subject(s)
Cholangiopancreatography, Endoscopic Retrograde , Humans , Cholangiopancreatography, Endoscopic Retrograde/methods , Sensitivity and Specificity , Bile Duct Neoplasms/pathology , Cytodiagnosis/methods , Bile Ducts/diagnostic imaging , Bile Ducts/pathology
9.
Sci Rep ; 14(1): 14904, 2024 06 28.
Article in English | MEDLINE | ID: mdl-38942924

ABSTRACT

Telocytes are closely associated with the regulation of tissue smooth muscle dynamics in digestive system disorders. They are widely distributed in the biliary system and exert their influence on biliary motility through mechanisms such as the regulation of CCK and their electrophysiological effects on smooth muscle cells. To investigate the relationship between telocytes and benign biliary diseases,such as gallbladder stone disease and biliary dilation syndrome, we conducted histopathological analysis on tissues affected by these conditions. Additionally, we performed immunohistochemistry and immunofluorescence double staining experiments for telocytes. The results indicate that the quantity of telocytes in the gallbladder and bile duct is significantly lower in pathological conditions compared to the control group. This reveals a close association between the decrease in telocyte quantity and impaired gallbladder motility and biliary fibrosis. Furthermore, further investigations have shown a correlation between telocytes in cholesterol gallstones and cholecystokinin-A receptor (CCK-AR), suggesting that elevated cholesterol levels may impair telocytes, leading to a reduction in the quantity of CCK-AR and ultimately resulting in impaired gallbladder motility.Therefore, we hypothesize that telocytes may play a crucial role in maintaining biliary homeostasis, and their deficiency may be associated with the development of benign biliary diseases, including gallstone disease and biliary dilation.


Subject(s)
Cholelithiasis , Gallbladder , Telocytes , Telocytes/metabolism , Telocytes/pathology , Cholelithiasis/pathology , Cholelithiasis/metabolism , Humans , Gallbladder/pathology , Gallbladder/metabolism , Female , Male , Bile Ducts/pathology , Bile Ducts/metabolism , Middle Aged , Aged , Dilatation, Pathologic
10.
Pathol Int ; 74(6): 337-345, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38787324

ABSTRACT

To improve the efficiency of pathological diagnoses, the development of automatic pathological diagnostic systems using artificial intelligence (AI) is progressing; however, problems include the low interpretability of AI technology and the need for large amounts of data. We herein report the usefulness of a general-purpose method that combines a hyperspectral camera with machine learning. As a result of analyzing bile duct biopsy and bile cytology specimens, which are especially difficult to determine as benign or malignant, using multiple machine learning models, both were able to identify benign or malignant cells with an accuracy rate of more than 80% (93.3% for bile duct biopsy specimens and 83.2% for bile cytology specimens). This method has the potential to contribute to the diagnosis and treatment of bile duct cancer and is expected to be widely applied and utilized in general pathological diagnoses.


Subject(s)
Bile Duct Neoplasms , Bile Ducts , Machine Learning , Humans , Bile Duct Neoplasms/pathology , Bile Duct Neoplasms/diagnosis , Bile Ducts/pathology , Biopsy/methods , Male , Female , Aged , Middle Aged , Bile/cytology , Hyperspectral Imaging/methods , Artificial Intelligence , Cytodiagnosis/methods , Cytology
11.
Biomaterials ; 310: 122621, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38815455

ABSTRACT

In vitro models of the human liver are promising alternatives to animal tests for drug development. Currently, primary human hepatocytes (PHHs) are preferred for pharmacokinetic and cytotoxicity tests. However, they are unable to recapitulate the flow of bile in hepatobiliary clearance owing to the lack of bile ducts, leading to the limitation of bile analysis. To address the issue, a liver organoid culture system that has a functional bile duct network is desired. In this study, we aimed to generate human iPSC-derived hepatobiliary organoids (hHBOs) consisting of hepatocytes and bile ducts. The two-step differentiation process under 2D and semi-3D culture conditions promoted the maturation of hHBOs on culture plates, in which hepatocyte clusters were covered with monolayered biliary tubes. We demonstrated that the hHBOs reproduced the flow of bile containing a fluorescent bile acid analog or medicinal drugs from hepatocytes into bile ducts via bile canaliculi. Furthermore, the hHBOs exhibited pathophysiological responses to troglitazone, such as cholestasis and cytotoxicity. Because the hHBOs can recapitulate the function of bile ducts in hepatobiliary clearance, they are suitable as a liver disease model and would be a novel in vitro platform system for pharmaceutical research use.


Subject(s)
Bile Ducts , Hepatocytes , Induced Pluripotent Stem Cells , Organoids , Humans , Induced Pluripotent Stem Cells/cytology , Induced Pluripotent Stem Cells/drug effects , Organoids/drug effects , Organoids/cytology , Hepatocytes/cytology , Hepatocytes/drug effects , Hepatocytes/metabolism , Liver/cytology , Cell Differentiation/drug effects , Pharmaceutical Research/methods
12.
Biochim Biophys Acta Mol Basis Dis ; 1870(6): 167225, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38749218

ABSTRACT

BACKGROUND: Acute kidney injury (AKI) causes distant liver injury, to date, which causes poor outcomes of patients with AKI. Many studies have been performed to overcome AKI-associated liver injury. However, those studies have mainly focused on hepatocytes, and AKI-induced liver injury still remains a clinical problem. Here, we investigated the implication of cholangiocytes and their primary cilia which are critical in final bile secretion. Cholangiocyte, a lining cell of bile ducts, are the only liver epithelial cell containing primary cilium (a microtubule-based cell surface signal-sensing organelle). METHODS: Cystathione γ-lyase (CSE, a transsulfuration enzyme) deficient and wild-type mice were subjected to kidney ischemia followed by reperfusion (KIR). Some mice were administered with N-acetyl-cysteine (NAC). RESULTS: KIR damaged hepatocytes and cholagiocytes, disrupted cholangiocytes primary cilia, released the disrupted ciliary fragments into the bile, and caused abnormal bile secretion. Glutathione (GSH) and H2S levels in the livers were significantly reduced by KIR, resulting in increased the ratio oxidized GSH to total GSH, and oxidation of tissue and bile. CSE and cystathione ß-synthase (CBS) expression were lowered in the liver after KIR. NAC administration increased total GSH and H2S levels in the liver and attenuated KIR-induced liver injuries. In contrast, Cse deletion caused the reduction of total GSH levels and worsened KIR-induced liver injuries, including primary cilia damage and abnormal bile secretion. CONCLUSIONS: These results indicate that KIR causes cholangiocyte damage, cholangiocytes primary cilia disruption, and abnormal bile secretion through reduced antioxidative ability of the liver.


Subject(s)
Bile , Cilia , Reperfusion Injury , Animals , Reperfusion Injury/metabolism , Reperfusion Injury/pathology , Cilia/metabolism , Cilia/pathology , Mice , Bile/metabolism , Male , Acute Kidney Injury/metabolism , Acute Kidney Injury/pathology , Mice, Inbred C57BL , Glutathione/metabolism , Mice, Knockout , Liver/pathology , Liver/metabolism , Hepatocytes/metabolism , Hepatocytes/pathology , Cystathionine gamma-Lyase/metabolism , Cystathionine gamma-Lyase/genetics , Kidney/metabolism , Kidney/pathology , Hydrogen Sulfide/metabolism , Hydrogen Sulfide/pharmacology , Bile Ducts/pathology , Bile Ducts/metabolism , Epithelial Cells/metabolism , Epithelial Cells/pathology
13.
BMC Gastroenterol ; 24(1): 163, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38745150

ABSTRACT

BACKGROUND: The liver regeneration is a highly complicated process depending on the close cooperations between the hepatocytes and non-parenchymal cells involving various inflammatory cells. Here, we explored the role of myeloid-derived suppressor cells (MDSCs) in the processes of liver regeneration and liver fibrosis after liver injury. METHODS: We established four liver injury models of mice including CCl4-induced liver injury model, bile duct ligation (BDL) model, concanavalin A (Con A)-induced hepatitis model, and lipopolysaccharide (LPS)-induced hepatitis model. The intrahepatic levels of MDSCs (CD11b+Gr-1+) after the liver injury were detected by flow cytometry. The effects of MDSCs on liver tissues were analyzed in the transwell co-culture system, in which the MDSCs cytokines including IL-10, VEGF, and TGF-ß were measured by ELISA assay and followed by being blocked with specific antibodies. RESULTS: The intrahepatic infiltrations of MDSCs with surface marker of CD11b+Gr-1+ remarkably increased after the establishment of four liver injury models. The blood served as the primary reservoir for hepatic recruitment of MDSCs during the liver injury, while the bone marrow appeared play a compensated role in increasing the number of MDSCs at the late stage of the inflammation. The recruited MDSCs in injured liver were mainly the M-MDSCs (CD11b+Ly6G-Ly6Chigh) featured by high expression levels of cytokines including IL-10, VEGF, and TGF-ß. Co-culture of the liver tissues with MDSCs significantly promoted the proliferation of both hepatocytes and hepatic stellate cells (HSCs). CONCLUSIONS: The dramatically and quickly infiltrated CD11b+Gr-1+ MDSCs in injured liver not only exerted pro-proliferative effects on hepatocytes, but also accounted for the activation of profibrotic HSCs.


Subject(s)
CD11b Antigen , Liver Cirrhosis , Liver Regeneration , Mice, Inbred C57BL , Myeloid-Derived Suppressor Cells , Animals , Myeloid-Derived Suppressor Cells/metabolism , Myeloid-Derived Suppressor Cells/immunology , Mice , Liver Cirrhosis/pathology , Liver Cirrhosis/metabolism , Liver Regeneration/physiology , CD11b Antigen/metabolism , Male , Disease Models, Animal , Liver/pathology , Liver/metabolism , Vascular Endothelial Growth Factor A/metabolism , Carbon Tetrachloride , Chemical and Drug Induced Liver Injury/pathology , Chemical and Drug Induced Liver Injury/immunology , Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/physiopathology , Concanavalin A , Ligation , Lipopolysaccharides , Interleukin-10/metabolism , Transforming Growth Factor beta/metabolism , Hepatic Stellate Cells/metabolism , Coculture Techniques , Hepatocytes/metabolism , Hepatocytes/pathology , Bile Ducts
14.
J Surg Oncol ; 129(8): 1534-1541, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38736301

ABSTRACT

BACKGROUND AND OBJECTIVES: Intraoperative bile duct injury is a significant complication in laparoscopic cholecystectomy (LC). Near-infrared fluorescence cholangiography (NIFC) can reduce this complication. Therefore, determining the optimal indocyanine green (ICG) dosage for effective NIFC is crucial. This study aimed to determine the optimal ICG dosage for NIFC. METHODS: This was a prospective, randomized, double-blind clinical trial at a single tertiary referral center, including 195 patients randomly assigned to three groups: lower dose (0.01 mg/BMI) ICG (n = 63), medium dose (0.02 mg/BMI) ICG (n = 68), and higher dose (0.04 mg/BMI) ICG (n = 64). Surgeon satisfaction and detection rates for seven biliary structures were compared among the three dose groups. RESULTS: Demographic parameters did not significantly differ among the groups. The medium dose (72.1%) and higher dose ICG groups (70.3%) exhibited superior visualization of the common hepatic duct compared to the lower dose group (41.3%) (p < 0.001). No differences existed between the medium and higher dose groups. Similar trends were observed for the common bile duct and cystic common bile duct junction. CONCLUSIONS: In patients undergoing fluorescent laparoscopic cholecystectomy, the 0.02 mg/BMI dose of indocyanine green demonstrated better biliary structure detection rates than the 0.01 mg/BMI dose and was non-inferior to the 0.04 mg/BMI dose.


Subject(s)
Cholecystectomy, Laparoscopic , Indocyanine Green , Humans , Indocyanine Green/administration & dosage , Cholecystectomy, Laparoscopic/methods , Double-Blind Method , Female , Male , Prospective Studies , Middle Aged , Cholangiography/methods , Adult , Aged , Coloring Agents/administration & dosage , Bile Ducts
15.
Curr Med Sci ; 44(3): 485-493, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38748369

ABSTRACT

Intraductal papillary neoplasm of the bile duct (IPNB) is a heterogeneous disease similar to intraductal papillary mucinous neoplasm of the pancreas. These lesions have been recognized as one of the three major precancerous lesions in the biliary tract since 2010. In 2018, Japanese and Korean pathologists reached a consensus, classifying IPNBs into type l and type 2 IPNBs. IPNBs are more prevalent in male patients in East Asia and are closely related to diseases such as cholelithiasis and schistosomiasis. From a molecular genetic perspective, IPNBs exhibit early genetic variations, and different molecular pathways may be involved in the tumorigenesis of type 1 and type 2 IPNBs. The histological subtypes of IPNBs include gastric, intestinal, pancreaticobiliary, or oncocytic subtypes, but type 1 IPNBs typically exhibit more regular and well-organized histological features than type 2 IPNBs and are more commonly found in the intrahepatic bile ducts with abundant mucin. Due to the rarity of these lesions and the absence of specific clinical and laboratory features, imaging is crucial for the preoperative diagnosis of IPNB, with local bile duct dilation and growth along the bile ducts being the main imaging features. Surgical resection remains the optimal treatment for IPNBs, but negative bile duct margins and the removal of lymph nodes in the hepatic hilum significantly improve the postoperative survival rates for patients with IPNBs.


Subject(s)
Bile Duct Neoplasms , Humans , Bile Duct Neoplasms/pathology , Bile Duct Neoplasms/genetics , Carcinoma, Papillary/pathology , Carcinoma, Papillary/genetics , Male , Bile Ducts, Intrahepatic/pathology , Bile Ducts/pathology
16.
Hepatol Commun ; 8(6)2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38780302

ABSTRACT

BACKGROUND: The relationship between primary sclerosing cholangitis (PSC) and biliary bile acids (BAs) remains unclear. Although a few studies have compared PSC biliary BAs with other diseases, they did not exclude the influence of cholestasis, which affects the composition of BAs. We compared biliary BAs and microbiota among patients with PSC, controls without cholestasis, and controls with cholestasis, based on the hypothesis that alterations in BAs underlie the pathophysiology of PSC. METHODS: Bile samples were obtained using endoscopic retrograde cholangiopancreatography from patients with PSC (n = 14), non-hepato-pancreato-biliary patients without cholestasis (n = 15), and patients with cholestasis (n = 13). RESULTS: The BA profiles showed that patients with PSC and cholestasis controls had significantly lower secondary BAs than non-cholestasis controls, as expected, whereas the ratio of cholic acid/chenodeoxycholic acid in patients with PSC was significantly lower despite cholestasis, and the ratio of (cholic acid + deoxycholic acid)/(chenodeoxycholic acid + lithocholic acid) in patients with PSC was significantly lower than that in the controls with or without cholestasis. The BA ratio in the bile of patients with PSC showed a similar trend in the serum. Moreover, there were correlations between the alteration of BAs and clinical data that differed from those of the cholestasis controls. Biliary microbiota did not differ among the groups. CONCLUSIONS: Patients with PSC showed characteristic biliary and serum BA compositions that were different from those in other groups. These findings suggest that the BA synthesis system in patients with PSC differs from that in controls and patients with other cholestatic diseases. Our approach to assessing BAs provides insights into the pathophysiology of PSC.


Subject(s)
Bile Acids and Salts , Cholangitis, Sclerosing , Cholestasis , Cholangitis, Sclerosing/blood , Cholangitis, Sclerosing/microbiology , Humans , Male , Bile Acids and Salts/blood , Bile Acids and Salts/analysis , Bile Acids and Salts/metabolism , Female , Middle Aged , Adult , Cholestasis/blood , Cholestasis/microbiology , Cholangiopancreatography, Endoscopic Retrograde , Case-Control Studies , Aged , Bile Ducts/microbiology , Bile/metabolism , Bile/microbiology , Chenodeoxycholic Acid/analysis , Cholic Acid/analysis , Cholic Acid/blood
17.
Scand J Gastroenterol ; 59(8): 906-917, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38745449

ABSTRACT

OBJECTIVES: The gut-liver axis disruption is a unified pathogenetic principle of cholestatic liver disease (CSLD). Increased gut permeability is the leading cause of gut-liver axis disruption. HO-1 is capable of protecting against gut-liver axis injury. However, it has rarely been reported whether autophagy is involved in HO-1 protecting gut-liver barrier integrity and the underlying mechanism. MATERIALS AND METHODS: Mice underwent bile duct ligation (BDL) was established as CSLD model in vivo. Caco-2 cells with LPS treatment was established as in vitro cell model. Immunofluorescence, western blot and transepithelial electrical resistance (TER) assay were used to observe epithelial tight junction (TJ) and autophagy. Liver injury and fibrosis were evaluated as well through H&E staining, masson staining, sirius red staining and ELISA. RESULTS AND CONCLUSIONS: Our study demonstrated that the epithelial TJ and TER were notably reduced both in BDL mice and in LPS treated intestinal epithelial cells. Increased HO-1 expression could significantly induce intestinal epithelial cell autophagy. Additionally, this increased autophagy level reversed the reduction effects of BDL or LPS on epithelial TJ and TER in vivo and in vitro, therefore decreased transaminase level in serum and relieved liver fibrosis in BDL mice. Besides, increased autophagy level in turn upregulated the expression of HO-1 by p62 degradation of Keap1 and subsequent activation of Nrf2 pathway. Collectively, these results indicate that HO-1 reduces gut permeability by enhancing autophagy level in CSLD, the increased autophagy establishes a HO-1-p62-Nrf2 positive feedback loop to further improve gut-liver axis disruption. Therefore, our study confirms the critical role of autophagy in HO-1 ameliorating gut-liver axis injury during CSLD, highlighting HO-1 as a promising therapeutic target.


Subject(s)
Autophagy , Cholestasis , Disease Models, Animal , Heme Oxygenase-1 , NF-E2-Related Factor 2 , Permeability , Animals , NF-E2-Related Factor 2/metabolism , Mice , Humans , Heme Oxygenase-1/metabolism , Caco-2 Cells , Cholestasis/metabolism , Cholestasis/pathology , Male , Mice, Inbred C57BL , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Liver/metabolism , Liver/pathology , Tight Junctions/metabolism , Bile Ducts/surgery , Lipopolysaccharides , Signal Transduction , Membrane Proteins
18.
Surg Laparosc Endosc Percutan Tech ; 34(2): 201-205, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38571322

ABSTRACT

BACKGROUND: With the aging of the global population, the incidence rate of acute cholecystitis is increasing. Laparoscopic cholecystectomy is considered as the first choice to treat acute cholecystitis. How to effectively avoid serious intraoperative complications such as bile duct and blood vessel injury is still a difficult problem that puzzles surgeons. This paper introduces the application of laparoscopic cholecystectomy, a new surgical concept, in acute difficult cholecystitis. METHODS: This retrospective analysis was carried out from January 2019 to January 2021. A total of 36 patients with acute difficult cholecystitis underwent 3-step laparoscopic cholecystectomy. The general information, clinical features, surgical methods, surgical results, and postoperative complications of the patients were analyzed. RESULTS: All patients successfully completed the surgery, one of them was converted to laparotomy, and the other 35 cases were treated with 3-step laparoscopic cholecystectomy. Postoperative bile leakage occurred in 2 cases (5.56%), secondary choledocholithiasis in 1 case (2.78%), and hepatic effusion in 1 case (2.78%). No postoperative bleeding, septal infection, and other complications occurred, and no postoperative colon injury, gastroduodenal injury, liver injury, bile duct injury, vascular injury, and other surgery-related complications occurred. All 36 patients were discharged from hospital after successful recovery. No one died 30 days after surgery, and there was no abnormality in outpatient follow-up for 3 months after surgery. CONCLUSIONS: Three-step laparoscopic cholecystectomy seems to be safer and more feasible for acute difficult cholecystitis patients. Compared with traditional laparoscopic cholecystectomy or partial cholecystectomy, 3-step laparoscopic cholecystectomy has the advantages of safe surgery and less complications, which is worth trying by clinicians.


Subject(s)
Cholecystectomy, Laparoscopic , Cholecystitis, Acute , Humans , Cholecystectomy, Laparoscopic/methods , Retrospective Studies , Cholecystectomy/methods , Cholecystitis, Acute/surgery , Cholecystitis, Acute/etiology , Bile Ducts/injuries
19.
J Laparoendosc Adv Surg Tech A ; 34(4): 305-312, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38573163

ABSTRACT

Introduction: Percutaneous endoscopic biliary lithectomy (PEBL) can be performed through preexisting drain tracts, offering ductal clearance and definitive management for patients with complicated gallstone disease unable to undergo conventional therapy. The technique has not been widely adopted by general surgeons. Herein, we describe our technique with surgeon-performed PEBL and present initial results. Materials and Methods: A single institutional retrospective review of the electronic medical record was performed for patients who underwent percutaneous choledochoscopy between February 2019 and November 2020. All operations were performed by 1 of 2 board-certified general surgeons with fellowship training in surgical endoscopy. Preoperative, operative, and postoperative variables were analyzed using descriptive statistics. Results: Thirteen patients underwent PEBL. Seventeen total procedures were performed; 4 patients underwent repeat intervention. The diagnoses leading to PEBL were: cholelithiasis (8), choledocholithiasis (4), and recurrent pancreatitis (1). Complete ductal clearance was achieved in 9 patients (69.2%) during the initial procedure. The remaining 4 patients (30.8%) underwent repeat PEBL, at which point complete ductal clearance was then achieved. The percutaneous drain was removed at the time of final procedure in 5 patients (38.5%) or within 5 weeks in the remaining 8 (61.5%). No intraoperative complications occurred, and no pancreatic or biliary postoperative complications or recurrences were noted with a mean follow-up of 279 ± 240 days. Conclusion: Surgeon-performed PEBL is a safe and effective method of achieving biliary ductal clearance. The technique is readily achieved following basic endoscopic and fluoroscopic principles and should be understood by all physicians managing gallstone disease.


Subject(s)
Choledocholithiasis , Surgeons , Humans , Endoscopy , Fluoroscopy , Bile Ducts
20.
World J Gastroenterol ; 30(9): 1043-1072, 2024 Mar 07.
Article in English | MEDLINE | ID: mdl-38577180

ABSTRACT

Several diseases originate from bile duct pathology. Despite studies on these diseases, certain etiologies of some of them still cannot be concluded. The most common disease of the bile duct in newborns is biliary atresia, whose prognosis varies according to the age of surgical correction. Other diseases such as Alagille syndrome, inspissated bile duct syndrome, and choledochal cysts are also time-sensitive because they can cause severe liver damage due to obstruction. The majority of these diseases present with cholestatic jaundice in the newborn or infant period, which is quite difficult to differentiate regarding clinical acumen and initial investigations. Intraoperative cholangiography is potentially necessary to make an accurate diagnosis, and further treatment will be performed synchronously or planned as findings suggest. This article provides a concise review of bile duct diseases, with interesting cases.


Subject(s)
Bile Duct Diseases , Biliary Atresia , Choledochal Cyst , Infant , Child , Infant, Newborn , Humans , Bile Ducts/diagnostic imaging , Bile Ducts/surgery , Biliary Atresia/diagnosis , Biliary Atresia/surgery , Choledochal Cyst/diagnosis , Choledochal Cyst/diagnostic imaging , Bile Duct Diseases/diagnosis , Bile Duct Diseases/etiology , Bile Duct Diseases/therapy , Cholangiography
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