Spectra of well-differentiated neuroendocrine lesions in the extrahepatic biliary system: a case series.

AIMS: Neuroendocrine tumours (NETs) occurring in the extrahepatic biliary system are exceedingly rare. While NETs typically manifest as mass lesions, the occurrence of microscopic neuroendocrine cell proliferation without a distinct mass remains undocumented at this location. This study aims to characterise the clinicopathological features of a series of well-differentiated neuroendocrine lesions involving the extrahepatic biliary tree, including mass forming NETs and microscopic non-mass-forming neuroendocrine cell proliferation, designated neuroendocrine cell micronests (NCMs). METHODS AND RESULTS: Surgical resections of NETs/NCMs involving the extrahepatic bile ducts and gallbladder were identified from electronic pathology databases among seven institutions spanning from January 2011 to September 2023. Clinical and histological findings were recorded. Ten patients (four female, six male: age range = 34-75 years) were included in the study. Histopathological examination revealed visible mass-forming lesions in four cases (1.6-14.0 cm in size), identified in the gallbladder (n = two) or extrahepatic bile duct (n = two), all diagnosed as well-differentiated NETs. The remaining six cases revealed incidental non-mass-forming NCMs in either the cystic duct (n = two), common bile duct (n = three) or gallbladder (n = one), ranging from < 0.1 to 0.4 cm; four were associated with biliary lithiasis. No evidence of metastasis or recurrence was seen in the follow-up period (range = 0.1-11.2 years). CONCLUSIONS: This study highlights the spectrum of extrahepatic biliary well-differentiated neuroendocrine lesions, ranging from incidental microscopic NCMs to grossly apparent mass-forming NETs, potentially requiring different clinical management. Noteworthy is the frequent association of incidental microscopic neuroendocrine cell proliferations with biliary lithiasis, indicating a potential neuroendocrine metaplastic pathogenesis that merits further exploration.

Single-Cell RNA Sequencing of Sox17-Expressing Lineages Reveals Distinct Gene Regulatory Networks and Dynamic Developmental Trajectories.

During early embryogenesis, the transcription factor SOX17 contributes to hepato-pancreato-biliary system formation and vascular-hematopoietic emergence. To better understand Sox17 function in the developing endoderm and endothelium, we developed a dual-color temporal lineage-tracing strategy in mice combined with single-cell RNA sequencing to analyze 6934 cells from Sox17-expressing lineages at embryonic days 9.0-9.5. Our analyses showed 19 distinct cellular clusters combined from all 3 germ layers. Differential gene expression, trajectory and RNA-velocity analyses of endothelial cells revealed a heterogenous population of uncommitted and specialized endothelial subtypes, including 2 hemogenic populations that arise from different origins. Similarly, analyses of posterior foregut endoderm revealed subsets of hepatic, pancreatic, and biliary progenitors with overlapping developmental potency. Calculated gene-regulatory networks predict gene regulons that are dominated by cell type-specific transcription factors unique to each lineage. Vastly different Sox17 regulons found in endoderm versus endothelial cells support the differential interactions of SOX17 with other regulatory factors thereby enabling lineage-specific regulatory actions.

Three-dimensional magnetic resonance cholangiography is superior to two-dimensional single-shot magnetic resonance cholangiography for visualization and image quality of the feline and canine biliary tract: A postmortem study.

Magnetic resonance cholangiography (MRC) is an established diagnostic tool for noninvasive assessment of the biliary tract in humans. It has also been found to be feasible in companion animals, but no published studies have compared MRC sequences in veterinary medicine. The present study is part of a prospective, observational, analytical investigation on MR cholangiopancreatography performed on the donated bodies of 12 cats and eight dogs. The main aim of this study was to compare the images of 2D-SSh-TSE-MRC and 3D-TSE-MRC sequences for visualization and image quality of the feline and canine biliary tract. Both sequences are T2-weighted and noncontrast. Three independent readers scored the visibility of four segments of the biliary tract, namely the gallbladder (GB), cystic duct, common bile duct (CBD), and extrahepatic ducts, and the image quality of the two MRC sequences using five-point Likert scales. Wilcoxon signed-rank test was used to compare the scores between the MRC sequences separately for cats and dogs. Inter- and intraobserver agreements were measured using Gwet's AC2 with linear weighting. The 3D-TSE-MRC images were scored significantly higher than the 2D-SSh-TSE-MRC for both visibility and image quality (P < .001-.016 for cats, P = .008-.031 for dogs); the only exception was GB in dogs. In both cats and dogs, interobserver agreement for segment visibility and image quality ranged from slight to substantial in 2D-SSh-TSE-MRC and from poor to almost perfect in 3D-TSE-MRC. Most of the assessments (73% for segment visibility and 66% for image quality) had substantial to almost perfect intraobserver agreement. Findings from the current study support the use of 3D-TSE-MRC over 2D-SSh-TSE-MRC for evaluation of the feline and canine biliary tract, but further studies on live animals are warranted.

Open hepatic artery flow with portal vein clamping protects against bile duct injury compared to pringles maneuver.

BACKGROUND: Conventional hepatic artery and portal vein clamping strategies can prevent blood loss and ischemia-reperfusion liver injury, and such preventative measures are the key to successful liver surgery. However, ischemic-induced damage to cholangiocytes is rarely considered. Here, we aimed to investigate the effect of different hepatic inflow interruption methods on bile duct injury. METHODS: Forty rats were randomly grouped as sham, Pringle maneuver (PM) and hepatic arterial blood flow open (HAFO) groups. We evaluated liver histology and function in liver sections, and biliary histology, cholangiocyte apoptosis and proliferation, cytokine production, and bile composition. RNA sequencing is performed to explore possible molecular mechanisms. The Blood-biliary barrier permeability and tight junctions were analyzed by HRP injection, immunofluorescence staining and analysis of ZO-1 expression by immunoblotting. RESULTS: HAFO significantly attenuated ischemia-induced liver injury and decreased ALT, ALP, TBIL, and DBIL levels in serum. The histopathological observations showed that bile duct injury in the PM group was more serious than that in the HAFO group. The numbers of apoptotic biliary epithelial cells in HAFO-treated rat bile ducta were lower than those in the PM group. RNA-seq showed that tight junctions may be related to the mechanism underlying the protective effect of HAFO, as shown by the reduced HRP levels and increased ZO-1 and claudin-1/3 expression in the HAFO group compared to the PM group. CONCLUSION: Compared with PM, HAFO alleviated the ischemic injury to the biliary system, which was characterized by decreased biliary epithelial cell apoptosis, reduced inflammatory responses and decreased blood-biliary-barrier permeability.

Cholangiopancreatography in cats: a post-mortem comparison of MRI with fluoroscopy, corrosion casting and histopathology.

In human medicine, magnetic resonance cholangiopancreatography (MRCP) is a valuable diagnostic tool for hepatobiliary and pancreatic diseases. In veterinary medicine, however, data evaluating the diagnostic value of MRCP are limited. The primary objectives of this prospective, observational, analytical investigation were to assess whether MRCP reliably visualizes the biliary tract and pancreatic ducts in cats without and with related disorders, and whether MRCP images and measurements of the ducts agree with those of fluoroscopic retrograde cholangiopancreatography (FRCP), corrosion casting and histopathology. A secondary objective was to provide MRCP reference diameters for bile ducts, GB, and pancreatic ducts. Donated bodies of 12 euthanized adult cats underwent MRCP, FRCP, and autopsy with corrosion casting of the biliary tract and pancreatic ducts using vinyl polysiloxane. Diameters of the biliary ducts, gallbladder (GB), and pancreatic ducts were measured using MRCP, FRCP, corrosion casts and histopathologic slides. There was an agreement between MRCP and FRCP in measuring diameters of the GB body, GB neck, cystic duct, and common bile duct (CBD) at papilla. Strong positive correlations existed between MRCP and corrosion casting for measuring GB body and neck, cystic duct, and CBD at the extrahepatic ducts' junction. In contrast to the reference methods, post-mortem MRCP did not visualize right and left extrahepatic ducts, and pancreatic ducts in most cats. Based on this study, MRCP with 1.5 Tesla can be regarded as a contributory method to improve the assessment of feline biliary tract and pancreatic ducts when their diameter is >1 mm.

Contrast-enhanced ultrasound of the spleen, pancreas and gallbladder in children.

Gray-scale and color/power Doppler ultrasound (US) are the first-line imaging modalities to evaluate the spleen, gallbladder and pancreas in children. The increasing use of contrast-enhanced ultrasound (CEUS) as a reliable and safe method to evaluate liver lesions in the pediatric population promises potential for imaging other internal organs. Although CEUS applications of the spleen, gallbladder and pancreas have been well described in adults, they have not been fully explored in children. In this manuscript, we present an overview of the applications of CEUS for normal variants and diseases affecting the spleen, gallbladder and pancreas. We highlight a variety of cases as examples of how CEUS can serve in the diagnosis and follow-up for such diseases in children. Our discussion includes specific examination techniques; presentation of the main imaging findings in various benign and malignant lesions of the spleen, gallbladder and pancreas in children; and acknowledgment of the limitations of CEUS for these organs.

Development and Assessment of Nano-Technologies for Cancer Treatment: Cytotoxicity and Hyperthermia Laboratory Studies.

Cancer treatment by magnetic hyperthermia offers numerous advantages, but for practical applications many variables still need to be adjusted before developing a controlled and reproducible cancer treatment that is bio-compatible (non-damaging) to healthy cells. In this work, Fe3O4 and CoFe2O4 were synthesized and systematically studied for the development of efficient therapeutic agents for applications in hyperthermia. The biocompatibility of the materials was further evaluated using HepG2 cells as biological model. Colorimetric and microscopic techniques were used to evaluate the interaction of magnetic nano-materials (MNMs) and HepG2 cells. Finally, the behavior of MNMs was evaluated under the influence of an alternating magnetic field (AMF), observing a more efficient temperature increment for CoFe2O4, a desirable behavior for biomedical applications since lower doses and shorter expositions to alternating magnetic field might be required.

Population-Based PBPK Model for the Prediction of Time-Variant Bile Salt Disposition within GI Luminal Fluids.

In vivo studies have shown cyclic bile salt (BS) outputs during fasting whereas higher amounts have been observed in fed states. This leads to fluctuations of intestinal BS concentrations ([BS]) that can affect the rate and extent of absorption of lipophilic drugs in particular. However, most PBPK models use fixed values of [BS] in fasted and fed states albeit with different values in different regions of the GI tract. During fasting, there is a relationship between gallbladder volume (GBV) and the phase of the Interdigestive Migrating Motor Complex cycle (IMMCc), showing cyclic GBV changes with periodic filling and emptying. This relationship is also affected by the origin of the IMMCc (antral or duodenal). In fed states, meta-analysis indicated that GB residual volume (% of fasting maximum) was 46.4 ± 27%CV and 30.7 ± 48%CV for low- and high-fat meals, respectively. The corresponding values for the duration of the emptying phase were for low fat meals 0.72h ± 1%CV and for high fat meals 1.17h ± 37%CV. The model, the Advanced Dynamic Bile Salt Model (ADBSM), was built bottom-up and its parameters were not fitted against in vivo measurements of [BS]. It involved update of the dynamic luminal fluid volumes model based on meta-analysis of available imaging data. The ADBSM is incorporated into the Simcyp (v18r2) PBPK simulator. The model predictivity was good (within 1.25-fold error for 11/20 of the clinical studies) and was assessed against clinical studies of luminal [BS] that provide only the type of meal (i.e., low- or high-fat), the timing of the meal and/or water intake events, and the number and age range of the study participants. The model is also an important component of models capturing enterohepatic recirculation of drug and metabolite. Further work is required to validate the current model and compare to simpler models with respect to drug absorption, especially of the lipophilic compounds.

Patient radiation dose in percutaneous biliary interventions: recommendations for DRLs on the basis of a multicentre study.

OBJECTIVE: Percutaneous biliary interventions (PBIs) can be associated with a high patient radiation dose, which can be reduced when national diagnostic reference levels (DRLs) are kept in mind. The aim of this multicentre study was to investigate patient radiation exposure in different percutaneous biliary interventions, in order to recommend national DRLs. METHODS: A questionnaire asking for the dose area product (DAP) and the fluoroscopy time (FT) in different PBIs with ultrasound- or fluoroscopy-guided bile duct punctures was sent to 200 advanced care hospitals. Recommended national DRLs are set at the 75th percentile of all DAPs. RESULTS: Twenty-three facilities (9 interventional radiology depts. and 14 gastroenterology depts.) returned the questionnaire (12%). Five hundred sixty-five PBIs with 19 different interventions were included in the analysis. DAPs (range 4-21,510 cGy·cm2) and FTs (range 0.07-180.33 min) varied substantially depending on the centre and type of PBI. The DAPs of initial PBIs were significantly (p < 0.0001) higher (median 2162 cGy·cm2) than those of follow-up PBIs (median 464 cGy·cm2). There was no significant difference between initial PBIs with ultrasound-guided bile duct puncture (2162 cGy·cm2) and initial PBIs with fluoroscopy-guided bile duct puncture (2132 cGy·cm2) (p = 0.85). FT varied substantially (0.07-180.33 min). CONCLUSIONS: DAPs and FTs in percutaneous biliary interventions showed substantial variations depending on the centre and the type of PBI. PBI with US-guided bile duct puncture did not reduce DAP, when compared to PBI with fluoroscopy-guided bile duct puncture. National DRLs of 4300 cGy·cm2 for initial PBIs and 1400 cGy·cm2 for follow-up PBIs are recommended. KEY POINTS: • DAPs and FTs in percutaneous biliary interventions showed substantial variations depending on the centre and the type of PBI. • PBI with US-guided bile duct puncture did not reduce DAP when compared to PBI with fluoroscopy-guided bile duct puncture. • DRLs of 4300 cGy·cm2for initial PBIs (establishing a transhepatic tract) and 1400 cGy·cm2for follow-up PBIs (transhepatic tract already established) are recommended.

Misleading findings of liver-specific MR contrast agent for radiological diagnosis of cysto-biliary communication in hydatid cysts.

OBJECTIVE: To investigate the effectiveness of gadoxetic acid-enhanced magnetic resonance cholangiopancreatography (CE-MRCP) and T2-weighted half-Fourier acquisition single-shot turbo spin-echo (T2W HASTE) sequences for diagnosis of cysto-biliary communication in hydatid cysts compared to surgical results. METHODS: Preoperative abdominal magnetic resonance imaging examinations of patients who underwent surgery for hepatic hydatid cysts were reviewed by two radiologists retrospectively. A total of 45 patients with hydatid cysts were included. Of 45, 27 also had CE-MRCPs. T2W HASTE sequences and CE-MRCPs were investigated separately for cysto-biliary communication. The relationship between radiological and surgical results was analyzed. The interobserver agreement was evaluated. RESULTS: Of 45 hydatid cysts, there were surgically proven 21 cysts without biliary communications and 24 cysts with biliary communications. All cysts with biliary communications were shown on T2W HASTE sequences. There was no leakage of gadoxetic acid into these cysts (n = 24). Sensitivity, specificity, negative predictive value, positive predictive value (PPV), and accuracy of diagnosis of cyst with biliary communication on T2W HASTE sequences was 100%, 63.64%, 100%, 66.67%, and 78.95%, respectively. Specificity (77.78%), PPV (87.50%), and accuracy (91.30%) were increased in ≥ 10 cm cysts. There was almost perfect interobserver agreement (K = 0.81-1.00). CONCLUSION: Leakage of gadoxetic acid inside the cyst indicates biliary communication. However, the lack of leakage does not rule out cysto-biliary communication. When biliary communication is clearly shown on T2W HASTE sequences, it should be reported as cysto-biliary communication even if there is no leakage of gadoxetic acid into the cyst on CE-MRCP.

Telocytes and interstitial cells of Cajal in the biliary system.

A novel type of interstitial tissue cells in the biliary tree termed telocytes (TCs), formerly known as interstitial Cajal-like cells (ICLCs), exhibits very particular features which unequivocally distinguish these cells from interstitial cells of Cajal (ICCs) and other interstitial cell types. Current research substantiates the existence of TCs and ICCs in the biliary system (gallbladder, extrahepatic bile duct, cystic duct, common bile duct and sphincter of Oddi). Here, we review the distribution, morphology and ultrastructure of TCs and ICCs in the biliary tree, with emphasis on their presumptive roles in physiological and pathophysiological processes.

The Density of Interstitial Cells of Cajal Is Diminished in Choledochal Cysts.

BACKGROUND AND AIMS: Interstitial cells of Cajal (ICC) have been shown to be present in the extrahepatic biliary tract of animals and humans. However, ICC distribution in choledochal cysts (CC) has not been investigated. A study was conducted to investigate the distribution of ICC in the extrahepatic biliary tract, including CC, in pediatric human specimens. METHOD: The specimens were divided into two main groups as gallbladders and common bile ducts. Gallbladders were obtained from the cholelithiasis, CC operations and autopsies. Common bile ducts were obtained from autopsies. Tissues were stained using c-kit immunohistochemical staining. ICC were assessed semi-quantitatively by applying morphological criteria and were counted as the number of cells/0.24 mm(2) in each area under light microscopy. RESULTS: A total of 35 gallbladders and 14 CC were obtained from operations. Ten gallbladders plus common bile ducts were obtained from autopsies. The mean numbers of ICC in the gallbladders of cholelithiasis and the gallbladders of CC were 12.2 ± 4.9 and 5.3 ± 1.2, respectively (p = 0.003). The mean numbers of ICC in the common bile ducts and CC were 9.8 ± 2.9 and 3.4 ± 1.4, respectively (p = 0.001). CONCLUSION: The scarcity of ICC in the extrahepatic biliary tract may be responsible for the etiopathogenesis of the CC.

Diverse functions of SOX9 in liver development and homeostasis and hepatobiliary diseases.

The liver is the central organ for digestion and detoxification and has unique metabolic and regenerative capacities. The hepatobiliary system originates from the foregut endoderm, in which cells undergo multiple events of cell proliferation, migration, and differentiation to form the liver parenchyma and ductal system under the hierarchical regulation of transcription factors. Studies on liver development and diseases have revealed that SRY-related high-mobility group box 9 (SOX9) plays an important role in liver embryogenesis and the progression of hepatobiliary diseases. SOX9 is not only a master regulator of cell fate determination and tissue morphogenesis, but also regulates various biological features of cancer, including cancer stemness, invasion, and drug resistance, making SOX9 a potential biomarker for tumor prognosis and progression. This review systematically summarizes the latest findings of SOX9 in hepatobiliary development, homeostasis, and disease. We also highlight the value of SOX9 as a novel biomarker and potential target for the clinical treatment of major liver diseases.

Atlas for Cholangioscopy and Cholecystoscopy: A Primer for Diagnostic and Therapeutic Endoscopy in the Biliary Tree and Gallbladder.

Percutaneous endoscopy of the biliary system (cholangioscopy) and gallbladder (cholecystoscopy) has significantly impacted diagnostic and therapeutic approaches to many diseases in interventional radiology, overcoming previous challenges related to scope size and rigidity. The current endoscopes offer enhanced maneuverability within narrow tubular structures such as bile ducts. Before endoscopy, reliance on 2D imaging modalities limited real-time visualization during percutaneous procedures. Percutaneous endoscopy provides 3D perspectives, enabling a better appreciation of normal structures, targeted biopsy of lesions, and accurate deployment of therapeutic interventions. This review aims to explore percutaneous endoscopic findings across various biliary and gallbladder pathologies.

Pancreatic congenital anomalies and their features on CT and MR imaging: a pictorial review.

OBJECTIVE: To review the congenital anomalies of the pancreas with their main clinical manifestations and key imaging findings on CT and MRI. BACKGROUND AND CLINICAL SIGNIFICANCE: Anomalies of pancreatic development are frequent and generally asymptomatic, but can mimic and predispose individuals to pancreatic or peripancreatic pathologies, such as pancreatitis or malignancy. Their correct diagnosis may help avoid unnecessary further investigations and procedures, or establish adequate treatment when they manifest clinically. Differentiating pancreatic congenital anomalies from their main radiological mimics constitutes a challenge for the radiologist and requires familiarity with key imaging findings. CONCLUSION: The imaging findings of CT and MRI are essential for the correct diagnosis of congenital pancreatic anomalies.

Novel definition of textbook outcome in biliary system cancers and its influence on patients' survival and quality of life.

BACKGROUND: The definition of textbook outcome in biliary system cancers is a developing concept in need of expansion and investigation of its association with survival and quality of life. METHODS: In this original research, we developed a novel "all or none" textbook outcome definition which addresses the rapid recovery of post-surgical indexes, in addition to short-term mortality, hospital re-admission, prolonged stay, surgical margin and postoperative complications. Based on the fulfillment of relevant criteria, patients were divided into textbook outcome and non-textbook outcome groups and their characteristics and survival data were analyzed. A customized "quality of life" questionnaire was developed to address short-term recovery and post-discharge life quality of patients. Association with quality of life improvement was then investigated. RESULTS: A total of 129 patients were included. Textbook outcome was achieved in 25.58% of patients (37.04% of gallbladder cancer patients and 17.8% of cholangiocarcinoma patients). Compared to non-textbook outcome group, patients with textbook outcome had lower rate of pre-operative biliary drainage (p = 0.026), higher rate of normal preoperative liver function (p < 0.001) and tumor markers (p = 0.001), reduced perioperative bleeding (p = 0.006) and blood transfusion (p = 0.005), and higher rate of N0 stage cases (p = 0.008). Textbook outcome was also associated with enhanced survival, significantly in older patients (<65 years) (1-year survival rate: 100% vs. 78.57% (p = 0.108), 2-year survival rate: 87.5% vs. 44% (p = 0.046)). Finally, textbook outcome was significantly associated with enhanced basic daily performance (p < 0.001), social life performance (p = 0.033), and personal evaluation (p < 0.001), and thus improved quality of life (p < 0.001). CONCLUSIONS: The novel definition of textbook outcome was able to address the specific nature of recovery after resection of biliary system cancers. Expanding the scope of textbook outcome and addressing the influence on survival and quality of life provides a comprehensive concept able to reflect physical, psychological and functioning enhancements in patients recovery.

Percutaneous cholecystoduodenal stent as a definite treatment for acute cholecystitis in elderly or comorbid patients: a bicentric retrospective study

PURPOSE: To investigate the safety and efficacy of percutaneous cholecystoduodenal stent (CDS) placement to prevent recurrence of acute cholecystitis in patients who were unfit for cholecystectomy. METHODS: Between April 2016 and January 2022, 46 patients [median age (range) = 81 (37-99) years; men = 15] with acute cholecystitis who were unfit for surgery underwent percutaneous cholecystostomy followed by a CDS placement in two institutions. Plastic stents of three different materials were used [polyethylene, polyurethane (PU), and polycarbonate (PCB)-based PU]. Clinical outcomes, including technical and clinical success rates and early (<30 days) and delayed adverse events, were retrospectively assessed by stent type. RESULTS: CDS placement was technically successful in 39 patients. Clinical success, defined as cholecystostomy catheter removal, was achieved in 35 of 39 patients. Immediate complications, such as acute pancreatitis and peritonitis, occurred in two patients. Two patients experienced recurrent cholecystitis during a 113-day follow-up (range, 3-1,723). Three-stent groups had significantly different delayed complications on Fisher's exact test (P = 0.021). The Bonferroni post-hoc analysis showed the PCB-PU group tended to have fewer complications than the PU group (P = 0.060). CONCLUSION: CDS placement is applicable in treating acute cholecystitis patients who were initially unfit for surgery, but further investigation is needed. Although it was not statistically significant, a PCB-PU stent can be suitable for this use because it tends to have fewer delayed complications and is equipped with a drawstring and side holes.

Hexafluoropropylene oxide trimer acid (HFPO-TA) disturbs embryonic liver and biliary system development in zebrafish.

Hexafluoropropylene oxide trimer acid (HFPO-TA), a novel alternative to perfluorooctanoic acid (PFOA), has emerged as a potential environmental pollutant. Here, to investigate the toxic effects of HFPO-TA on liver and biliary system development, zebrafish embryos were exposed to 0, 50, 100, or 200 mg/L HFPO-TA from 6 to 120 h post-fertilization (hpf). Results showed that the 50 % lethal concentration (LC50) of HFPO-TA was 231 mg/L at 120 hpf, lower than that of PFOA. HFPO-TA exposure decreased embryonic hatching, survival, and body length. Furthermore, HFPO-TA exerted higher toxicity at the specification stage than during the differentiation and maturation stages, leading to small-sized livers in Tg(fabp10a: DsRed) transgenic larvae and histopathological changes. Significant decreases in the mRNA expression of genes related to liver formation were observed. Alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and direct bilirubin (DBIL) levels were significantly increased. HFPO-TA decreased total cholesterol (TCHO) and triglyceride (TG) activities, disturbed lipid metabolism through the peroxisome proliferator-activated receptor (PPAR) pathway, and induced an inflammatory response. Furthermore, HFPO-TA inhibited intrahepatic biliary development in Tg(Tp1:eGFP) transgenic larvae and interfered with transcription of genes associated with biliary duct development. HFPO-TA reduced bile acid synthesis but increased bile acid transport, resulting in disruption of bile acid metabolism. Therefore, HFPO-TA influenced embryonic liver and biliary system morphogenesis, caused liver injury, and may be an unsafe alternative for PFOA.

Computed tomographic quantitative evaluation of common bile duct size in normal dogs: A reference range study considering body weight.

Introduction: Common bile duct (CBD) measurements are important for the evaluation of biliary systemic disorders. However, in veterinary medicine, reference ranges for specific body weights (BW) and correlation between CBD diameter and BW have not been studied. This study aimed to establish normal reference ranges of CBD diameter for different BW groups and to analyse correlation between CBD diameter and BW in dogs without hepatobiliary disease. Additionally, normal reference ranges of CBD to aorta ratio (CBD: Ao ratio) were established which is not affected by BW. Methods: CBD diameter was measured at three different sites: porta hepatis (PH), duodenal papilla (DP) level and mid-portion (Mid) between these points using computed tomography (CT) in 283 dogs without hepatobiliary disease. Results: The reference range of CBD diameter at PH level: 1.69 ± 0.29 mm (Class 1; 1 kg ≤ BW < 5 kg), 1.92 ± 0.35 mm (Class 2; 5 kg ≤ BW < 10 kg), 2.20 ± 0.43 mm (Class 3; 10 kg ≤ BW < 15 kg), 2.79 ± 0.49 mm (Class 4; 15 kg ≤ BW < 30 kg); Mid-level: 2.06 ± 0.25 mm (Class 1), 2.43 ± 0.37 mm (Class 2), 2.74 ± 0.52 mm (Class 3), 3.14 ± 0.44 mm (Class 4); DP level: 2.33 ± 0.34 mm (Class 1), 2.90 ± 0.36 mm (Class 2), 3.35 ± 0.49 mm (Class 3), and 3.83 ± 0.50 mm (Class 4). There was a significant difference in CBD diameter at each level among all BW groups. Furthermore, BW and CBD diameter showed positive linear correlation at each level. We devised CBD: Ao ratio at each level that showed no significant difference between the different BW groups; PH level: 0.34 ± 0.05; Mid-level: 0.42 ± 0.06; DP level: 0.47 ± 0.06. Conclusion: In conclusion, since the CBD diameter for each BW is significantly different, different normal reference ranges of CBD diameter should be applied for each BW, and the CBD: Ao ratio can be used regardless of the BW.