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.

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.

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.

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.

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.

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.

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.

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.

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.

Statins associate with lower risk of biliary tract cancers: A systematic review and meta-analysis.

BACKGROUND: Biliary tract cancers (BTCs), encompassing cholangiocarcinoma (CCA), gallbladder (GBC), and ampulla of Vater cancers (AVC), are common hepatobiliary cancer after hepatocellular carcinoma with a high mortality rate. As there is no effective chemopreventive agent to prevent BTCs, this study aimed to explore the role of statins on the risk of BTCs. METHODS: PubMed, Embase, and Cochrane Library from inception until 24 April 2020 were searched according to the Meta-Analyses of Observational Studies in Epidemiology (MOOSE) guidelines. The adjusted risk ratios (aRRs) of BTCs and individual cancer were pooled using a random-effects model. RESULTS: Eight observational studies (3 cohort and 5 case-control studies) were included with 10,485,231 patients. The median age was 68.0 years (IQR: 67.0-71.5) and 48.3% were male. Statins were associated with a lower risk of all BTCs (aRR: 0.67; 95% CI: 0.51-0.87). The pooled aRR for CCA was 0.60 (95% CI: 0.38-0.94) and GBC was 0.78 (95% CI: 0.68-0.90). There was only one study on AVC with aRR of 0.96 (95% CI: 0.66-1.41). The pooled aRR for lipophilic and hydrophilic statins was 0.78 (95% CI: 0.69-0.88) and 0.70 (95% CI: 0.61-0.80), respectively. The effects were attenuated in studies that adjusted for aspirin and/or non-steroidal anti-inflammatory drugs (aRR: 0.80, 95% CI: 0.72-0.89) and metformin (aRR: 0.80, 95% CI: 0.72-0.90). CONCLUSIONS: Statins, both lipophilic and hydrophobic, were associated with a lower risk of BTCs, particularly CCA and GBC.

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.

Long-Term Characteristics of Human-Derived Biliary Organoids under a Single Continuous Culture Condition.

Organoids have been used to investigate the three-dimensional (3D) organization and function of their respective organs. These self-organizing 3D structures offer a distinct advantage over traditional two-dimensional (2D) culture techniques by creating a more physiologically relevant milieu to study complex biological systems. The goal of this study was to determine the feasibility of establishing organoids from various pediatric liver diseases and characterize the long-term evolution of cholangiocyte organoids (chol-orgs) under a single continuous culture condition. We established chol-orgs from 10 different liver conditions and characterized their multicellular organization into complex epithelial structures through budding, merging, and lumen formation. Immunofluorescent staining, electron microscopy, and single-nucleus RNA (snRNA-seq) sequencing confirmed the cholangiocytic nature of the chol-orgs. There were significant cell population differences in the transcript profiles of two-dimensional and organoid cultures based on snRNA-seq. Our study provides an approach for the generation and long-term maintenance of chol-orgs from various pediatric liver diseases under a single continuous culture condition.

Acute infection with Platynosomum illiciens (Trematoda: Dicrocoeliidae) as a clinically relevant and potentially fatal disease in Falco sparverius (Aves: Falconidae) in Brazil.

Platynosomum illiciens is a dicrocoeliid trematode from the biliary tract of warm-blooded vertebrates (felines, primates, marsupials, and birds) reported in different parts of the world. Although the veterinary relevance of platynosomosis in mammals, especially in domestic felines, has been increasingly evidenced in the scientific literature, studies involving avian disease caused by P. illiciens are comparatively scarce. In the present study, a female specimen of the American kestrel, Falco sparverius L., found dead, in November 2019, in Brazil, was necropsied. Parietal biliary effusion in the celomatic cavity was observed, suggesting biliary transudation and gallbladder stasis, which possibily preceded the distension and rupture of gallbladder noted during necropsy. In the microscopic analysis of the bile content, small trematodes were found and characterized as immature stages of Platynosomum after the morphological study. Partial sequences of the cox-1 gene enabled the identification of P. illiciens, with 100% similarity with previously sequenced sympatric isolates from mammals. The finding of immature specimens in a ruptured gallbladder strongly suggests a role for the parasite in biliary flow dysfunction, indicating acute platynosomosis as a clinically relevant and potentially fatal condition that has not yet been discussed.

Case Report: Imaging Features of Gallbladder Sessile Polyp Confirmed by Contrast-Enhanced Ultrasonography and Dynamic Computed Tomography in a Dog With Asymptomatic Chronic Cholecystitis.

A 6-year-old dog was presented for health screening. It never suffered from any disease. Ultrasonography confirmed mass-like thickening with irregular margins protruding toward the gallbladder (GB) lumen. On contrast-enhanced ultrasonography (CEUS) and dynamic computed tomography (CT), contrast enhancement of the corresponding structures was confirmed in arterial phase. After cholecystectomy, cauliflower-like sessile polyps were identified. Histopathological examination revealed chronic lymphoplasmacytic cholecystitis. Bile culture revealed Escherichia coli growth. Our novel findings suggest that chronic cholecystitis should be considered as a differential diagnosis if contrast-enhanced sessile polyps of the GB are found on CEUS and dynamic CT.

Anatomical and radiographic distribution of hepatic artery and biliary duct system applied to biochemical parameters indicative to hepatobiliary disease in Egyptian donkey (Equus asinus).

The current study was performed on ten adult Egyptian donkeys of both sexes for anatomical and radiographic studies in addition to six other donkeys for enzymatic, biochemical and statistical analysis. The aim was to illustrate the normal hepatic arterial and biliary distribution using different anatomic techniques and radiographic imaging besides, establishing an accurate laboratory profile specific for donkeys that used as standard indicators for hepatobiliary dysfunction. The right branch of the hepatic artery in donkey forms a curved arch erupting five branches, unlike the left branch that erupts six branches, being the direct continuation of the main hepatic artery. The caudate lobe artery either originated from the hepatic artery or its right division. The common hepatic duct represented a very clear enlargement called 'gall tank' at its terminal pouring intestinal end and compensating absence of gall bladder, cystic and common bile ducts. The intrahepatic biliary distribution is characterized by a segmental ramification into dorsal, intermediate, and ventral branches of bile ductules especially noticed in the undivided right lobe and left lateral lobe. The quadrate lobe is divided according to its biliary drainage into right and left parts where the former is drained by the left hepatic duct while the latter is drained through a branch from R. lobi medialis sinistri. The serum enzymatic activity was slightly similar to that of the horse while some biochemical parameters differentiating the donkey from the horse such as lowered total bilirubin, serum bile acids, and higher triglycerides, blood urea and prolonged prothrombin time.

Acute Cholecystitis Presenting With Septic Shock as the First Presentation in an Elderly Patient.

Gangrenous cholecystitis (GC), a severe complication of acute cholecystitis, is associated with higher morbidity and mortality rates than uncomplicated cholecystitis. In this report, we present the case of an 81-year-old female with diabetes mellitus and hypertension who presented in the emergency department complaining of severe generalized abdominal pain for 10 days. The pain was associated with nausea and vomiting. She had septic shock, prompting admission, and was eventually diagnosed with perforated GC. Interventional radiology was conducted, and a cholecystostomy tube was placed under radiology guidance with continuous daily irrigation and intravenous antibiotic coverage for four weeks. Subsequently, the patient's condition improved, and she was finally discharged.

Endoscopic ultrasound-guided portal vein coiling: troubleshooting interventional endoscopic ultrasonography.

Endoscopic ultrasound (EUS)-guided hepaticogastrostomy (HGS) is widely performed not only as an alternative to transpapillary biliary drainage, but also as primary drainage for malignant biliary obstruction. For anatomical reasons, this technique carries an unavoidable risk of mispuncturing intrahepatic vessels. We report a technique for troubleshooting EUS-guided portal vein coiling to prevent bleeding from the intrahepatic portal vein after mispuncture during interventional EUS. EUS-HGS was planned for a 59-year-old male patient with unresectable pancreatic cancer. The dilated bile duct (lumen diameter, 2.8 mm) was punctured with a 19-gauge needle, and a guidewire was inserted. After bougie dilation, the guidewire was found to be inside the intrahepatic portal vein. Embolizing coils were placed to prevent bleeding. Embolization coils were successfully inserted under stabilization of the catheter using a double-lumen cannula with a guidewire. Following these procedures, the patient was asymptomatic. Computed tomography performed the next day revealed no complications.