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Competing Interests: The authors have no conflicts of interests to disclose.

Background: Artificial intelligence is touted as the future of medicine. Classical algorithms for the detection of common bile duct stones (CBD) have had poor clinical uptake due to low accuracy. This study explores the challenges of developing and implementing a machine-learning model for the prediction of CBD stones in patients presenting with acute biliary disease (ABD)., Methods: All patients presenting acutely to Christchurch Hospital over a two-year period with ABD were retrospectively identified. Clinical data points including lab test results, demographics and ethnicity were recorded. Several statistical techniques were utilised to develop a machine-learning model. Issues with data collection, quality, interpretation and barriers to implementation were identified and highlighted., Results: Issues with patient identification, coding accuracy, and implementation were encountered. In total, 1315 patients met inclusion criteria. Incorrect international classification of disease 10 (ICD-10) coding was noted in 36% (137/382) of patients recorded as having CBD stones. Patients with CBD stones were significantly older and had higher aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin and gamma-glutamyl transferase (GGT) levels (p < 0.001). The no information rate was 81% (1070/1315 patients). The optimum model developed was the gradient boosted model with a PPV of 67%, NPV of 87%, sensitivity of 37% and a specificity of 96% for common bile duct stones., Conclusion: This paper highlights the utility of machine learning in predicting CBD stones. Accuracy is limited by current data and issues do exist around both the ethics and practicality of implementation. Regardless, machine learning represents a promising new paradigm for surgical practice.

Indirect (IBil), direct (DBil) and total (TBil) bilirubin are important clinical indicators of hepatobiliary diseases, which require rapid detection in diagnosis and treatment. IBil and DBil have a structural relationship with several macromolecules in hepatobiliary metabolism. Here, the rapid analysis models for bilirubin indicators using serum visible-near-infrared (Vis-NIR) spectroscopy were established. Norris derivative filter with optimisation was used for spectral pretreatment; the optimal parameters (derivative order, number of smoothing points, number of differential gaps) were (2, 15, 9) for IBil; (2, 13, 9) for DBil, respectively. Equidistant combination-partial least squares (EC-PLS) was used for large-scale wavelength screening. Wavelength step-by-step phase-out PLS (WSP-PLS) was used for secondary wavelength optimisation. The wavelength models of the optimal EC-WSP-PLS for IBil and DBil included 11 and 18 wavelengths, respectively. In independent validation, the root-mean-square errors and correlation coefficient for prediction (SEP, R P ), and ratio of performance-to-deviation (RPD) were 0.90 μmol L -1 , 0.975, and 4.4 for IBil; 0.71 μmol L -1 , 0.955, and 3.3 for DBil, respectively. TBil was subjected to spectral analysis, and the summation of the prediction values of IBil and DBil was compared. The latter was obviously better, and SEP, R P , RPD were 0.82 μmol L -1 , 0.990, 7.1, respectively. The results for IBil, DBil and TBil indicated high correlation, low error and good overall prediction ability and confirmed the feasibility of the simultaneous analysis of bilirubin indicators through reagent-free serum Vis-NIR spectroscopy. The proposed method is crucial for the rapid screening of large populations and the treatment of hepatobiliary diseases., (Copyright © 2020. Published by Elsevier B.V.)

Comorbidity of hypertension and hepatobiliary pathology has negative medical and social consequences, including an increase in the indicators of hospital admissions, disability and mortality., Objective: The aim was to study the occurrence of hypertension combined with hepatobiliary diseases depending on social status, gender and age in 2003-2017 and their influence on indicators of metabolic processes in patients with a therapeutic profile., Methods: A cross-sectional study using the inpatients' medical record database of the clinic of Federal Research Centre for Basic and Translational Medicine (Novosibirsk, Russia), which collects demographics, diagnoses (using ICD-10 codes), procedures and examinations of all inpatients from 2003-2017 was conducted. The incidence of comorbidity of hypertension and hepatobiliary pathology depending on age, gender and social status, based on the analysis of 13496 medical records was examined. A comparative analysis of biochemical parameters characterizing the main types of metabolism (lipid, protein, carbohydrate and purine) was carried out in 3 groups of patients: with hypertension; with hepatobiliary pathology, and with a combined pathology., Results: During the years 2003-2005, there was the greatest frequency of this comorbidity in workers, in women, in the age group 60 years and older. In 2009-2017, the highest incidence was observed in the male administrative staff. In patients with this comorbidity, more pronounced changes in carbohydrate, protein, lipid and purine metabolism were found in comparison with groups of patients with isolated diseases., Conclusion: The results highlight the need to improve the system of prevention and treatment of comorbidity taking into account sex, age, occupation and features of metabolism., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Ceritinib demonstrated a statistically significant effect on the progression-free survival versus chemotherapy in patients with advanced anaplastic lymphoma kinase (ALK) rearrangement in non-small cell lung cancer (NSCLC) as the first therapy or after previous treatment with crizotinib and one or two prior chemotherapy regimens in global phase 3 studies. However, some serious adverse effects related to ceritinib therapy were reported across these clinical studies. Among them, a grade 3 and 4 increase in hepatobiliary enzymes was one of the common adverse events related to treatment with ceritinib. However, the pathology remains unclear. Previously, increased Interleukin (IL)-18 was observed in both biliary duct disease and liver disease. Therefore, we hypothesized that IL-18 is involved in the pathology of hepatobiliary adverse effects related to treatment with ceritinib and evaluated the serum IL-18., Case Presentation: The patient was a 53-year-old Japanese woman that we previously reported as having severe hepatobiliary adverse effects related to ceritinib therapy. Laboratory data, CT and MRI were obtained at each time point. IL-18 was evaluated by ELISA method at each time point. Immunochemical staining of liver tissue was performed as a standard protocol using antibodies against IL-18. Our records showed that the levels of serum IL-18 increased from the early stage of hepatobiliary adverse effects related to the treatment with ceritinib and were became worse with an increase in hepatobiliary enzymes and the progression of imaging abnormalities in the bile duct. Furthermore, IL-18 positive cells were detected in the inflammatory sites around the interlobular bile duct of the liver tissue., Conclusion: Our case report shows that the increase of serum IL-18 had a positive correlation with the progression of severe hepatobiliary adverse effects related to treatment with ceritinib and the involvement of IL-18 in the hepatobiliary inflammation by pathological evaluation. These results suggest that IL-18 could be a useful surrogate marker for the hepatobiliary toxicity of ceritinib. However, this is only one case report and further prospective observations will complement our data in the future.

Objectives: This pilot study aimed to determine the feasibility of serum values of osteonectin, adiponectin, transforming growth factor beta 1, and neurotensin being used in clinical practice to predict the severity of acute pancreatitis., Methods: Blood samples were collected from 45 consecutive newly diagnosed acute pancreatitis patients and 30 matched healthy controls. The 2 groups were matched according to age, sex, weight, height, diabetes, smoking, and alcohol consumption. The aforementioned markers were measured using enzyme-linked immunosorbent assay kits., Results: Characteristics of acute pancreatitis patients and healthy controls were comparable. Osteonectin values differed significantly (P < 0.0001). Median/lower quartile/upper quartile of osteonectin levels for acute pancreatitis patients and healthy controls were 263.5/110.3/490.36 and 63.2/46.1/87.2 ng/mL, respectively. Two patients died, 1 patient underwent necrosectomy, and 4 patients had a prolonged intensive care unit/hospital stay. Acute Physiology and Chronic Health Evaluation II and Systemic Inflammatory Response Syndrome scores neither predicted serum values of any of the measured substances nor the clinical outcome (need for intervention, prolonged intensive care unit/hospital stay and mortality). Osteonectin was the only independent predictor for clinical outcome (P = 0.007)., Conclusions: Serum osteonectin strongly discriminates healthy individuals from acute pancreatitis patients. Serum osteonectin shows promise in the prediction of the clinical outcome.

Purpose: To develop a model to predict successful bilirubin decrease following percutaneous biliary drain placement., Methods: A total of 257 patients who were identified having undergone percutaneous transhepatic biliary drain placement (PTBD) at our institution between 2002 and 2013 had their medical records and imaging reviewed. Of those, 190 of these patients met criteria and were used in the analysis. A regression model was performed on logarithm-transformed collected variables to predict post-drainage logarithmic transformed total bilirubin levels. A stepwise variable selection method based on Schwarz Bayesian Information Criterion was used to select the most closely associated variables. The model was validated with a Monte Carlo simulation. A short program was developed to calculate the point estimate using the model developed and compared to actual values., Results: The variables that best predicted bilirubin reduction were initial Tbl (PrTbl), INR and ALT. The selected model had a root mean squared error of 0.8. The model had a negative predictive value (PoTbl is below 2 mg/dL) of 83%., Conclusions: PTBD may not achieve decreasing bilirubin in patients with a malignant obstruction. This is an initial model that can help determine which patients may not benefit from PTBD placement. With more patients, the model's validity can be increased and provide useful clinical determinant to aide patient care.

Choledochal cyst is a cystic dilation of the biliary tree that can increase the risk of malignancy in bile ducts and the gallbladder. These are usually lined by bile duct epithelium, which may undergo intestinal and squamous metaplasia. This is the first report of clinically diagnosed type II choledochal cyst that is entirely lined by metaplastic stratified squamous epithelium, unlike most other cysts, which are histologically lined by bile duct epithelium. This observation can potentially explain the underlying pathogenic mechanism of rare reports of squamous cell carcinomas arising in bile duct systems.

Here, we present the case of a pediatric patient with newly diagnosed hepatocellular carcinoma causing central biliary obstruction and persistently elevated bilirubin of 3.0-4.3 mg/dl despite placement of bilateral internal-external biliary drains. The tumor was not resectable, and the patient was not a candidate for liver transplant due to nodal disease, for chemotherapy due to hyperbilirubinemia, or for local therapies aside from stereotactic body radiotherapy (SBRT). In this report, we discuss the successful use of SBRT in the management of this patient, and its role in allowing the patient to become a candidate for additional therapies., (© 2016 Wiley Periodicals, Inc.)

Laboratory evaluation of the hepatobiliary system has an important role in the diagnosis, monitoring, and assessment of patients with hepatobiliary diseases. Serum liver enzyme activities can be divided into markers of hepatocellular injury and cholestasis. Liver function can be assessed in several ways, including assessment of synthetic capacity, measurement of ammonia, and measurement of bile acids. It is essential to have an understanding of the performance characteristics and limitations of these tests in order to use them appropriately. This article reviews the laboratory parameters commonly used to aid diagnosing hepatobiliary disorders in dogs and cats., (Published by Elsevier Inc.)

Background and Aims: In patients who have undergone ERCP with biliary stenting for postsurgical bile leaks, the optimal method (ERCP or gastroscopy) and timing of stent removal is controversial. We developed a clinical prediction rule to identify cases in which a repeat ERCP is unnecessary., Methods: Population-based study of all patients who underwent ERCP for management of surgically induced bile leaks between 2000 and 2012. Multivariate and binary recursive partitioning analyses were performed to generate a rule predicting the absence of biliary pathology on repeat endoscopic evaluation., Results: A total of 259 patients were included. On multivariate analysis, postsurgical normal alkaline phosphatase (ALP; OR, 2.26; 95% CI, 1.03-4.99), time from surgery to first ERCP < 8 days (OR, 2.47; 95% CI, 1.15-5.31), and minor leak with no other pathology on initial ERCP (OR, 6.74; 95% CI, 1.75-25.89) were independently associated with the absence of persistent bile leak and other pathology on repeat ERCP. The derived rule included laparoscopic cholecystectomy, normal postsurgical ALP, minor leak with no other pathology on initial ERCP, and an interval from initial to repeat ERCP between 4 and 8 weeks. When all 4 criteria were met, the rule had a sensitivity of 94% (95% CI, 83%-99%) and a negative predictive value of 93% (95% CI, 81%-99%). Optimism-adjusted sensitivity and negative predictive value were 88% (95% CI, 76%-96%) and 86% (95% CI, 73%-96%), respectively., Conclusions: This clinical decision rule identifies patients who can have their biliary stents removed via gastroscopy, which may improve patient safety and healthcare utilization., (Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

The liver plays a crucial role in all aspects of coagulation because most factors that regulate procoagulation, anticoagulation, and fibrinolysis are produced, cleared, and/or activated in the liver. Establishing the coagulation status of an individual patient with hepatobiliary disease can therefore be challenging. Although, classically, patients with hepatobiliary disease were thought of as potentially hypocoagulable, hypercoagulability also occurs. The article summarizes the breadth of coagulation abnormalities that have been reported in dogs and cats with hepatobiliary disease and provides strategies to respond to bleeding and thrombotic risk., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: We conducted this prospective nested case-control study for the hepatic artery and portal vein hemodynamic changes after orthotopic liver transplantation., Methods: A total 128 cases of orthotropic liver transplantation were analyzed, including 25 cases of ischemic type biliary lesions (ITBL). The portal vein and hepatic artery flow velocities were detected by ultrasound on days 28, 42, and 84 after liver transplantation. In the GLM analysis of Lg(S/D), the P values of Group Effect, Time Effect, and Time×Group were 0.014, 0.376, and 0.008, respectively., Conclusion: Our results show a relatively reduced hepatic artery S/D in ITBL, especially in extrahepatic ITBL., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Soluble CD22 (sCD22) is a fragment of CD22, a B cell-specific membrane protein that negatively regulates B-cell receptor signaling. To date, sCD22 has only been regarded as a tumor marker of B-cell malignancies. Its expression in infectious diseases has not yet been assessed., Methods: Serum concentrations of sCD22, procalcitonin (PCT) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assays in patients with intra-abdominal Gram-negative bacterial infection. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic accuracy of these biomarkers in this type of infection. The correlations between biomarkers and the Acute Physiology and Chronic Health Evaluation (APACHE) II scores were also analyzed., Results: Concentrations of sCD22 were significantly elevated in patients with sepsis and the elevation is correlated with the severity of sepsis. sCD22 was also slightly elevated in patients with non-infected systemic inflammatory response syndrome or local infection. The diagnostic accuracy of sCD22 for sepsis was equivalent to that of PCT or IL-6. In addition, the correlation of sCD22 with APACHE II scores was stronger than that of PCT or IL-6., Conclusions: Serum sCD22 is a novel inflammatory mediator released during infection. This soluble biomarker plays a potential role in the diagnosis of Gram-negative bacterial sepsis, with a diagnostic accuracy as efficient as that of PCT or IL-6. Furthermore, sCD22 is more valuable to predict the outcomes in patients with sepsis than PCT or IL-6. The present study suggested that sCD22 might be potentially useful in supplementing current criteria for sepsis.

Routine biochemical tests generally include serum enzymes, proteins, and other markers useful for identifying hepatobiliary disease in dogs and cats. Obtaining results outside the reference intervals can occur with direct hepatocellular injury, enzyme induction by hepatocytes or biliary epithelium, or decreased hepatic function. However, detection of biochemical abnormalities does not necessarily indicate clinically significant disease. For a comprehensive approach to detection and treatment of hepatobiliary disease, the laboratory results must be correlated with the history and physical examination findings, diagnostic imaging results, and other assays., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: The role of M2-PK (pyruvate kinase) in bile has not been studied in comparison with brushings and carbohydrate antigen (CA) 19-9 in the diagnosis of malignant biliary strictures., Aim: To compare the diagnostic accuracy of biliary M2-PK with cytology and serum CA 19-9 METHODS: In this prospective cross-sectional study, bile was aspirated in 74 patients (discovery and validation cohort) undergoing endoscopic retrograde cholangiopancreatography. Levels of M2-PK were measured in bile and compared to brushings for cytology and CA 19-9., Results: In the discovery cohort, the median bile M2-PK levels were significantly elevated in patients with malignant biliary strictures [187.9 U/l (interquartile range (IQR) 3.5, 3626.8)] compared to those with benign biliary conditions and primary sclerosing cholangitis [0 U/l (IQR 0, 15)] (P = 0.007). A M2-PK cutoff value of 109.1 U/l distinguished malignant from benign conditions with a sensitivity and specificity of 52.9 and 94.1 %, respectively, and area under curve (AUC) of 0.77. The sensitivity of CA 19-9 and brushings in diagnosing cancer was 52.9 % and 11.1 % and specificity 94.1 and 100 %, respectively. The presence of elevated M2-PK >109.1 U/l or CA 19-9 >33 U/ml or positive brushing was 88.2 % sensitive and 88.2 % specific, AUC of 0.89 in the diagnosis of malignancy. The diagnostic accuracy was confirmed in the validation cohort., Conclusions: As a stand-alone factor, none of the markers were able to distinguish benign from malignant biliary strictures with a high sensitivity. However, a combination was highly sensitive in diagnosing malignant biliary strictures.

NSC-743380 (1-[(3-chlorophenyl)-methyl]-1H-indole-3-carbinol) is in early stages of development as an anticancer agent. Two metabolites reflect sequential conversion of the carbinol functionality to a carboxaldehyde and the major metabolite, 1-[(3-chlorophenyl)-methyl]-1H-indole-3-carboxylic acid. In an exploratory toxicity study in rats, NSC-743380 induced elevations in liver-associated serum enzymes and biliary hyperplasia. Biliary hyperplasia was observed 2 days after dosing orally for 2 consecutive days at 100mg/kg/day. Notably, hepatotoxicity and biliary hyperplasia were observed after oral administration of the parent compound, but not when major metabolites were administered. The toxicities of a structurally similar but pharmacologically inactive molecule and a structurally diverse molecule with a similar efficacy profile in killing cancer cells in vitro were compared to NSC-743380 to explore scaffold versus target-mediated toxicity. Following two oral doses of 100mg/kg/day given once daily on two consecutive days, the structurally unrelated active compound produced hepatic toxicity similar to NSC-743380. The structurally similar inactive compound did not, but, lower exposures were achieved. The weight of evidence implies that the hepatotoxicity associated with NSC-743380 is related to the anticancer activity of the parent molecule. Furthermore, because biliary hyperplasia represents an unmanageable and non-monitorable adverse effect in clinical settings, this model may provide an opportunity for investigators to use a short-duration study design to explore biomarkers of biliary hyperplasia., (Published by Elsevier Inc.)

Background: Living donor liver transplantation (LDLT) has been widely accepted over the past decade, and hepatic dysfunction often occurs in the donor in the early stage after liver donation. The present study aimed to evaluate the effect of intra-operative cholangiography (IOC) and parenchymal resection on liver function of donors in LDLT, and to assess the role of IOC in influencing the biliary complications and improving the overall outcome., Methods: Data from 40 patients who had donated their right lobes for LDLT were analyzed. Total bilirubin (TB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGT) at different time points were compared, and the follow-up data and the biliary complications were also analyzed., Results: The ALT and AST values were significantly increased after IOC (P<0.001) and parenchymal resection (P<0.001). However, the median values of TB, ALP and GGT were not significantly influenced by IOC (P>0.05) or parenchymal resection (P>0.05). The biochemical changes caused by IOC or parenchymal resection were not correlated with the degree of post-operative liver injury or the recovery of liver function. The liver functions of the donors after operation were stable, and none of the donors suffered from biliary stenosis or leakage during the follow-up., Conclusions: IOC and parenchymal resection may induce a transient increase in liver enzymes of donors in LDLT, but do not affect the recovery of liver function after operation. Moreover, the routine IOC is helpful to clarify the division line of the hepatic duct, thus reducing the biliary complication rate.

Aim: To evaluate the efficiency and safety of using statins in combination with ursodeoxycholic acid (UDCA) in patients with this or another liver disease at high risk for cardiovascular events (CVE)., Subjects and Methods: A register of 262 patients at high risk for CCE who needed statin therapy and have concomitant chronic liver and biliary tract diseases was created in 5 cities of the Russian Federation., Results: After addition of statins or adjustment of their doses, the patients were recommended to include UDCA into their therapy. Six months after stabilization of the dose of statins, the whole group showed a significant reduction in the levels of total cholesterol and low-density lipoprotein (LDL) cholesterol. Assessment of the laboratory parameters responsible for the safety of statin intake revealed no deterioration in the trend in the activity of alanine aminotransferase, aspartate aminotransferase, creatine phosphokinase, lactate dehydrogenase, as well as an increase in the serum level of bilirubin. The data obtained using a special questionnaire indicated that 196 patients had taken UDCA and 56 had not. The UDCA and non-UDCA subgroups did not differ in age, weight, or baseline lipid metabolic disturbances. An additional analysis showed that by the end of 6 months, the goal levels of LDL cholesterol in the UDCA and non-UDCA groups were reached in 37 and 20%, respectively (p = 0.01)., Conclusion: UDCA added to statin therapy in patients at high risk for CVE and concurrent liver diseases contributes to an additional reduction in total cholesterol and LDL cholesterol and prevents enhanced hepatic transaminase activities.

Objective: To determine signalments, clinical features, clinicopathologic variables, imaging findings, treatments, and survival time of cats with presumed primary copper-associated hepatopathy (PCH) and to determine quantitative measures and histologic characteristics of the accumulation and distribution of copper in liver samples of cats with presumed PCH, extrahepatic bile duct obstruction, chronic nonsuppurative cholangitis-cholangiohepatitis, and miscellaneous other hepatobiliary disorders and liver samples of cats without hepatobiliary disease., Design: Retrospective cross-sectional study., Animals: 100 cats with hepatobiliary disease (PCH [n = 11], extrahepatic bile duct obstruction [14], cholangitis-cholangiohepatitis [37], and miscellaneous hepatobiliary disorders [38]) and 14 cats without hepatobiliary disease., Procedures: From 1980 to 2013, cats with and without hepatobiliary disease confirmed by liver biopsy and measurement of hepatic copper concentrations were identified. Clinical, clinicopathologic, and imaging data were compared between cats with and without PCH., Results: Cats with PCH were typically young (median age, 2.0 years); clinicopathologic and imaging characteristics were similar to those of cats with other liver disorders. Copper-specific staining patterns and quantification of copper in liver samples confirmed PCH (on the basis of detection of > 700 μg/g of liver sample dry weight). Six cats with PCH underwent successful treatment with chelation (penicillamine; n = 5), antioxidants (5), low doses of elemental zinc (2), and feeding of hepatic support or high-protein, low-carbohydrate diets, and other hepatic support treatments. One cat that received penicillamine developed hemolytic anemia, which resolved after discontinuation of administration. Three cats with high hepatic copper concentrations developed hepatocellular neoplasia., Conclusions and Clinical Relevance: Results suggested that copper accumulates in livers of cats as primary and secondary processes. Long-term management of cats with PCH was possible.

Results: Basal and stimulated serum CCK concentrations were not statistically significant differences (p > 0.05) with the control group in patients studied in the whole and in patients subgroups, formed by the diagnosis of biliary pathology and the character of gallbladder emptying. Increased stimulated CCK concentration was found in patients with symptomatic variants. Reduce of serum-cholecystokinin concentration growth (ACCK) after intake of Sorbitol was revealed in subgroup of patients with low-symptom variant. Reduced sensitivity of the gallbladder to CCK was observed in subgroups of patients with gallbladder hypokinetic dyskinesia and one with symptomatic variant of biliary pathology., Conclusion: The sensitivity of the gallbladder neuromuscular apparatus to CCK is associated with clinical and functional variability of the biliary pathology.

A standard hepaticojejunostomy technique might be difficult to perform, especially when the bile duct is small and located deep in the liver hilum. Herein we present a new procedure, the Hand-Fan technique, that was used to enhance the exposure and ease the performance of these challenging anastomoses. Thirty-one patients who had had hepaticojejunostomy with this technique for bile duct injury and other benign biliary pathologies from July 2004 to June 2011 were included into the study. Median postoperative hospital stay was 7 days (6-25 days) and median follow-up time was 33 months (2-84 months). Liver function tests revealed that the blood bilirubin levels of the patients were normalized after hepaticojejunostomy. Follow-up showed that there were no signs of clinical recurrence or impaired bile flow. The Hand-Fan technique considerably facilitates challenging hepaticojejunostomies. Surgeon's comfort is exceptional and the clinical results are satisfactory.

Aim: To investigate the effect of different secondary warm ischemia time (SWIT) on bile duct injury in liver-transplanted rats., Methods: Forty-eight male inbred Sprague-Dawley rats were randomly assigned into four groups: a sham-operation group and three groups with secondary biliary warm ischemia time of 0 min, 10 min and 20 min. A rat model of autologous liver transplantation under ether anesthesia was established, and six rats were killed in each group and blood samples and the median lobe of the liver were collected for assay at 6 h and 24 h after hepatic arterial reperfusion., Results: With prolongation of biliary warm ischemia time, the level of vascular endothelial growth factor-A was significantly decreased, and the value at 24 h was higher than that at 6 h after hepatic arterial reperfusion, but with no significant difference. The extended biliary SWIT led to a significant increase in bile duct epithelial cell apoptosis, and a decrease in the number of blood vessels, the bile duct surrounding the blood vessels and bile duct epithelial cell proliferation in the early postoperative portal area. Pathologic examinations showed that inflammation of the rat portal area was aggravated, and biliary epithelial cell injury was significantly worsened., Conclusion: A prolonged biliary warm ischemia time results in aggravated injury of the bile duct and the surrounding vascular plexus in rat autologous orthotopic liver transplantation.

Objectives: After portosystemic anastomoses for biliopathy, some patients continue to suffer biliary obstruction. The effects of splenectomy and devascularization of the abdominal oesophagus and upper stomach are unclear. The aim of the current study was to determine the features of portal biliopathy (PB) in patients with non-cirrhotic portal hypertension, and to investigate outcomes in these patients after surgical procedures., Methods: A retrospective study of 56 patients who underwent surgery for PB during 1996-2010 was conducted. Data on presenting features, treatment received and outcomes were analysed., Results: In total, 41 of these patients had extrahepatic portal venous obstruction and 15 had non-cirrhotic portal fibrosis. Forty patients underwent shunt surgery and 16 underwent splenectomy and devascularization. Median bilirubin levels fell from 1.8 mg/dl (range: 0.4-5.9 mg/dl) to 1.0 mg/dl (range: 0.3-5.4 mg/dl) after shunt surgery and from 1.9 mg/dl (range: 0.6-4.0 mg/dl) to 1.2 mg/dl (range: 0.6-5.2 mg/dl) after splenectomy-devascularization. On follow-up, five of 33 patients had persistent jaundice after successful shunt surgery. These patients had a history of multiple endoscopic stentings and three patients had demonstrated a dominant common bile duct stricture preoperatively., Conclusions: Portal biliopathy was reversed in 38 of 43 patients by either portosystemic shunting or splenectomy-devascularization. In five patients, direct biliary decompressive procedures were required because of shunt blockage or a non-reversible biliary stricture., (© 2012 International Hepato-Pancreato-Biliary Association.)

Objectives: C-type natriuretic peptide (CNP) might be an important regulator of vasodilatation, fluid and sodium balance in liver cirrhosis. We aimed at assessing its regulation and prognostic relevance in liver disease patients., Design and Methods: We analyzed NT-proCNP serum levels in 193 patients with chronic liver diseases and 43 healthy controls., Results: Serum NT-proCNP concentrations were significantly elevated in liver disease patients compared to healthy controls, with highest levels in established hepatic cirrhosis, independent of disease etiology. NT-proCNP was associated with complications of liver diseases and portal hypertension, namely ascites, esophageal varices and hepatic encephalopathy. Circulating NT-proCNP correlated inversely with renal function. Importantly, elevated NT-proCNP levels were identified as a predictor of mortality or necessity for transplantation. NT-proCNP levels >2 pmol/L indicated adverse prognosis (sensitivity 66.7%, specificity 72.8%, RR 5.4 [95%-CI 2.6-11.2])., Conclusions: Serum NT-proCNP is elevated in advanced liver diseases and has prognostic value in cirrhotic patients., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Opisthorchiasis caused by Opisthorchis viverrini infection induces hepatobiliary disease (HBD)-associated cholangiocarcinoma (CCA) via a chronic inflammatory immune response. Here, we evaluated specific IgG and IgA antibodies against different fractions of O. viverrini antigen in residents from an endemic community in Northeast Thailand with varying hepatobiliary abnormalities. Crude somatic O. viverrini antigen was purified into three fractions (viz., P1, P2 and P3) by gel infiltration chromatography and these served as antigens for detection of fluke-specific IgG and IgA antibodies by enzyme-linked immunosorbent assay (ELISA). The results revealed fluke-specific IgG and IgA antibody levels-against these antigens from subjects with O. viverrini-positive HBD-higher than in subjects with O. viverrini-negative HBD. Interestingly, the rank of fluke-specific IgG (and not IgA) antibody levels against crude extract and P1 antigens was CCA>severe HBD>mild HBD>healthy individuals. Purified antigens reduced cross-reactivity with other parasites compared to the crude antigen. Multiple linear regression analysis showed that HBD status was significantly associated with the liver fluke-specific IgG antibody against purified antigens. These results suggest that purified O. viverrini-antigen improves serodiagnosis for the evaluation of opisthorchiasis-associated HBD, and may be useful in the screening of opisthorchiasis in subjects at risk of developing CCA., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: Anti-angiogenic agents are now being clinically evaluated for the treatment of pancreatic cancer and a detailed investigation of the angiogenic profile of pancreatic cancer is needed. The aim of this study was to evaluate the plasma concentrations of angiogenesis-related molecules in patients with pancreatic cancer, compared with those with other diseases., Methods: Plasma samples obtained from 45 patients with pancreatic cancer were analyzed and compared with those from 9 patients with pancreatitis, 16 patients with benign hepatobiliary diseases and 58 patients with colorectal cancers. The plasma levels of angiogenesis-related molecules including angiopoietin-2, follistatin, granulocyte-colony stimulating factor, hepatocyte growth factor, interleukin-8, leptin, platelet-derived growth factor beta polypeptide, platelet endothelial cell adhesion molecule-1 and vascular endothelial growth factor were determined using an antibody suspension bead arrays system., Results: The plasma levels of all the angiogenesis-related molecules were not increased in patients with pancreatic cancer, compared with those with pancreatitis and benign hepatobiliary diseases, whereas the levels of those with colorectal cancer were markedly increased. The plasma interleukin-8 concentration was significantly elevated in patients with distant metastases and was associated with a poor treatment outcome of chemotherapy in patients with pancreatic cancer., Conclusions: The plasma levels of angiogenesis-related molecules were not elevated in patients with pancreatic cancer, compared with those with benign diseases or colorectal cancer. The plasma interleukin-8 level may be a novel biomarker for the response to chemotherapy in patients with pancreatic cancer and warrants further prospective study.

Aim: To determine the role of circulating tumor cells (CTCs) in prediction of the overall survival of patients with advanced malignant biliary tract obstruction., Methods: We investigated the prognostic value of CTCs by examining two markers, cytokeratin (CK) 19 and human telomerase reverse transcriptase (hTERT) mRNA, in 40 patients diagnosed with advanced malignant biliary tract diseases. Quantitative real-time reverse transcription polymerase chain reaction was used to detect CK19 and hTERT mRNA in the peripheral blood of these patients. Overall survival was analyzed using the Kaplan-Meier method and Cox regression modeling., Results: Positive CK19 and hTERT mRNA expression was detected in 45% and 60%, respectively, of the 40 patients. Univariable analysis indicated that positive CK19 mRNA expression was significantly associated with worse overall survival (P = 0.009). Multivariable analysis determined that positive CK19 mRNA expression, patient's age and serum bilirubin were each independently associated with overall survival., Conclusion: CK19 mRNA expression levels in peripheral blood appear to provide a valuable marker to predict the overall survival of patients with advanced malignant biliary tract obstruction.

Paired serum bile acid (SBA) samples from 30 dogs with presumptive hepatobiliary disease and 30 apparently healthy dogs were submitted to three diagnostic laboratories to validate agreement between these facilities. Sensitivities and specificities ranged from 50% to 70% and from 74% to 85%, respectively, for all laboratories. The κ index confirmed almost perfect agreement between laboratories. Variation in sample handling and processing by different laboratories should not be considered a primary factor when aberrant SBA values are encountered. Documenting agreement between laboratories is essential as inconsistencies could direct unnecessary medical or surgical intervention when patients are evaluated at different hospitals during the course of their disease.

Elevation of carbohydrate antigen 19-9 has been observed in jaundiced patients with benign biliary tract diseases. No clear answer has explained that relationship. Patients with liver hydatidosis and frank intrabiliary rupture could present obstructive jaundice due to the presence of liver cyst material in the bile duct. We present two cases of huge elevation of carbohydrate antigen 19-9 in jaundiced patients with liver hydatidosis and biliocystic communication, and we assess the different theories presented in the medical literature today.

The purposes of this retrospective study were to assess the prevalence of gallbladder sludge (GBS) in a population of cats presented for abdominal ultrasound in a teaching hospital and to determine its association with increased serum alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total bilirubin (TB). Gallbladder sludge was detected in 152 (14%) of the cats undergoing abdominal ultrasound between 2004 and 2008. This population was compared to a control group of 32 cats without GBS. Alanine aminotransferase, ALP, and TB mean values were significantly higher in cats with GBS than in controls (P ≤ 0.0005) and odds for increased values in cats with GBS were 4.2 [95% confidence interval (CI): 1.6 to 11.0], 9.5 (95% CI: 2.2 to 41.7), and 4.1 (95% CI: 1.5 to 11.5), respectively (P ≤ 0.007). In conclusion, GBS is an uncommon ultrasonographic finding in cats that is predictive of increased liver enzymes and TB. More studies are needed to establish potential links between GBS and hepatobiliary disease in cats.

Background: Differentiating between benign and malignant causes of obstructive jaundice can be challenging, even with the advanced imaging and endoscopic techniques currently available. In patients with obstructive jaundice, the predictive accuracy of bilirubin levels at presentation was examined in order to determine whether such data could be used to differentiate between malignant and benign disease., Methods: A total of 1,026 patients with obstructive jaundice were identified. Patients were divided into benign and malignant groups. The benign patients were subgrouped into those with choledocholithiasis and those with inflammatory strictures of the biliary tree. Bilirubin levels at presentation and other demographic data were obtained from case records., Results: Area under the curve (AUC) values for bilirubin as a predictor of malignancy were highly significant for all benign presentations and for those with benign biliary strictures (AUC: 0.8 for both groups; P < 0.001). A bilirubin level > 100 µmol/l was determined to provide the optimum sensitivity and specificity for malignancy in all patients and in those without choledocholithiasis (71.9% and 86.9%, 71.9% and 88.0%, respectively). The application of a bilirubin level > 250 µmol/l achieved specificities of 97.1% and 98.0% in each subgroup of patients, respectively., Conclusions: In patients with obstructive jaundice, bilirubin levels in isolation represent an important tool for discriminating between benign and malignant underlying causes., (© 2011 International Hepato-Pancreato-Biliary Association.)

Aim: To study prevalence of gastrointestinal symptoms (GIS) including gall-bladder dysfunction (GBD) in coronary patients after acute coronary event (ACE) and effects of early physical exercise (PE) of moderate intensity in coronary patients with GBD on efficacy of outpatient rehabilitation., Material and Methods: A two-stage trial was conducted. Stage 1: 237 coronary patients responded to questionnaire detecting incidence of GIS including GBD 8 weeks after ACE. Stage 2: 85 coronary patients with verified GBD were examined for efficacy of rehabilitation. Of them, 43 patients entered PE group while 42 patients entered a control group. The latter received standard therapy without PE. The efficacy of the treatment was evaluated by clinical, device and biochemical findings at baseline and 12 months later., Results: Of 237 coronary patients 217 (91.7%) patients 2 months after ACE had symptoms of coronary insufficiency, 192 (81.3%) had GIS, 78.9% had GBD. Patients from PE group significantly improved exercise tolerance (bicycle exercise test reached 79.3 +/- 15 and 121.3 +/- 14.5 bt (p < 0.05), respectively. These patients demonstrated improvement of gall-bladder contraction, a decrease in the level of total cholesterol from 6.12 +/- 0.4 to 4.7 +/- 0.2 mmol/l (p < 0.05), of LDLP cholesterol from 3.85 +/- 0.21 to 2.86 +/- 0.32 mmol/l (p < 0.05), thioldisulphide coefficient from 13 +/- 0.3 to 2.7 +/- 0.4 (p < 0.01). The intergroup analysis 12 months after the study revealed significant differences in favor of the PE group. A weekly number of anginal attacks reduced from 5.1 +/- 1.5 to 1.3 +/- 1.4 (p < 0.01)., Conclusion: The exercise program is rather effective and can be practiced outpatiently in coronary patients after ACE associated with GBD. It can be also used for secondary prophylaxis of cholestasis in coronary patients with biliary problems.

Background and Aim: Macrophage inhibitory cytokine (MIC-1) and tissue polypeptide-specific antigen (TPS) are novel markers for several inflammatory and malignant disorders, and there are no sufficient data about the utility of these antigens as serum tumor markers. We aimed at measuring the serum levels of MIC-1 and TPS in patients with benign and malignant pancreatobiliary diseases and at determining their diagnostic efficacy., Patients and Methods: Sera collected from patients with pancreatic adenocarcinomas (56 cases), periampullary carcinomas other than pancreatic carcinomas (15 cases), benign pancreatic diseases (31 cases), benign biliary diseases (15 cases) and healthy volunteers (33 cases) were analyzed for MIC-1 and TPS and the results were compared with CA 19-9., Results: Serum MIC-1 levels increased more significantly in patients with pancreatic carcinomas than in patients with benign pancreatobiliary diseases and healthy controls (p < 0.05). MIC-1 has a similar sensitivity (81%) but a lower specificity (73 vs. 97%) than CA 19-9 in patients with pancreatic carcinomas. Serum TPS was comparable among patients with malignant and benign pancreatobiliary diseases, and healthy controls., Conclusion: MIC-1 is a valuable tumor marker for the diagnosis of pancreatic cancer. It has a good correlation with CA 19-9. TPS has no diagnostic importance to differentiate pancreatobiliary diseases. and IAP., (Copyright © 2011 S. Karger AG, Basel.)

Background: We postulated that the abundance of various metabolites in blood would facilitate the diagnosis of pancreatic and biliary lesions, which could potentially prevent unnecessary surgery., Methods: Serum samples from patients with benign hepatobiliary disease (n = 43) and from patients with pancreatic cancer (n = 56) were examined by ¹H NMR spectroscopy to quantify 58 unique metabolites. Data were analyzed by "targeted profiling" followed by supervised pattern recognition and orthogonal partial least-squares discriminant analysis (O-PLS-DA) of the most significant metabolites, which enables comparison of the whole sample spectrum between groups., Results: The metabolomic profile of patients with pancreatic cancer was significantly different from that of patients with benign disease (AUROC, area under the ROC curve, = 0.8372). Overt diabetes mellitus (DM) was identified as a possible confounding factor in the pancreatic cancer group. Thus, diabetics were excluded from further analysis. In this more homogeneous pancreatic cancer group, compared with benign cases, serum concentrations of glutamate and glucose were most elevated on multivariate analysis. In benign cases, creatine and glutamine were most abundant. To examine the usefulness of this test, a comparison was made to age- and gender-matched controls with benign lesions that mimic cancer, controlling also for presence of jaundice and diabetes (n = 14 per group). The metabolic profile in patients with pancreatic cancer remained distinguishable from patients with benign pancreatic lesions (AUROC = 0.8308)., Conclusions: The serum metabolomic profile may be useful for distinguishing benign from malignant pancreatic lesions., Impact: Further studies will be required to study the effects of jaundice and diabetes. A more comprehensive metabolomic profile will be evaluated using mass spectrometry., (©2010 AACR.)

Objective: To determine: (1) changes in blood ammonia, bile acid (BA), bilirubin, triglyceride, and glucose concentrations and liver enzyme activities in perioperative colic patients and (2) the association between these laboratory findings and short-term survival., Design: Prospective observational clinical study., Animals: Thirty-two adult horses undergoing exploratory celiotomy for colic., Interventions: None., Measurements and Main Results: Blood samples were collected preoperatively and at 24-36 and 72-84 hours postoperatively and analyzed for blood ammonia, BA, bilirubin, triglyceride, and glucose concentrations and sorbitol dehydrogenase (SDH) and gamma glutamyl transferase (GGT) activities. Short-term survival was defined as survival to hospital discharge. Data were analyzed using a Fisher's exact test and analysis of variance. Mildly increased blood ammonia concentrations were present in 2 horses at admission. Postoperative blood ammonia concentrations were within reference intervals in all horses. There were increases in liver enzyme activities as well as in BA, triglyceride, and total bilirubin concentrations. Horses with markedly increased admission BA concentrations and SDH activities did not survive. BA concentrations and SDH activities decreased postoperatively. There was no association between GGT activity and survival; GGT activity remained increased postoperatively. Blood triglyceride concentration was increased in almost all horses postoperatively; horses that did not survive had higher triglyceride concentrations at 24-36 hours postoperatively than horses that survived., Conclusion: Alterations in metabolism and hepatobiliary function are common in colic patients. The results of this study provide further prognostic indices for colic patients and highlight areas for improvement in patient management., (© Veterinary Emergency and Critical Care Society 2010.)

Background and Aims: Infection with Helicobacter hepaticus has been associated with development of hepatocellular carcinoma and gallstones in animal models. In humans, however, the association of H. hepaticus infection with biliary and pancreatic diseases has not been elucidated. The aim of this study was to serologically examine the prevalence of H. hepaticus infection in patients with biliary and pancreatic diseases., Methods: Serum samples obtained from 55 patients with cholelithiasis, 18 with bile duct or gallbladder cancer and 19 with pancreatic cancer were studied. Sera were obtained from 34 control subjects who underwent endoscopy and were diagnosed as not having peptic ulcers or cancers. Seropositivity of H. hepaticus was examined by western blot analysis using a H. hepaticus-specific antigen. To validate the specificity, positive sera were also tested after absorption with H. hepaticus whole-cell sonicate. Serum samples were also tested for the presence of anti-Helicobacter pylori antibody., Results: Prevalence of antibody to H. hepaticus-specific antigen in patients with bile tract cancer was 38.8% and was significantly higher than in control subjects (13.1%, P < 0.05). Prevalence of antibody to H. hepaticus-specific antigen was 18.2% and 10.5% in patients with cholelithiasis and pancreatic cancer, respectively. Seropositivity for H. pylori was similar in all groups. Detection of the H. hepaticus-specific band was significantly decreased after the sera were absorbed with H. hepaticus whole-cell sonicate., Conclusion: Infection with H. hepaticus might be associated with bile duct cancer. Results obtained from absorbed sera suggested high specificity of the western blot analysis.

Background: Cholangiocarcinoma is an aggressive tumor with a tendency for local invasion and distant metastases. Timely diagnosis is very important because surgical resection (R0) remains the only hope for a cure. However, at present, there is no available tumor marker that can differentiate cholangiocarcinoma from benign bile duct disease. Previous studies have demonstrated that matrix metalloproteinase (MMP)-7 and MMP-9 are frequently expressed in cholangiocarcinoma specimens., Methods: This study was designed to determine whether the serum levels of MMP-7 and MMP-9 can discriminate cholangiocarcinoma patients from benign biliary tract disease patients in comparison to carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). We measured the level of CEA, CA19-9, MMP-7 and MMP-9 in the serum of 44 cholangiocarcinoma and 36 benign biliary tract diseases patients., Results: Among the serum levels of CEA, CA19-9, MMP-7 and MMP-9, only the serum MMP-7 level was significantly higher in the patients with cholangiocarcinoma (8.9 +/- 3.43 ng/ml) compared to benign biliary tract disease patients (5.9 +/- 3.03 ng/ml) (p < 0.001). An receiver operating characteristic (ROC) curve analysis revealed that the detection of the serum MMP-7 level is reasonably accurate in differentiating cholangiocarcinoma from benign biliary tract disease patients (area under curve = 0.73; 95% CI = 0.614-0.848). While the areas under the curve of the ROC curves for CEA, CA19-9 and MMP-9 were 0.63 (95% CI = 0.501-0.760), 0.63 (95% CI = 0.491-0.761) and 0.59 (95% CI = 0.455-0.722), respectively., Conclusion: Serum MMP-7 appears to be a valuable diagnostic marker in the discrimination of cholangiocarcinoma from benign biliary tract disease. Further prospective studies for serum MMP-7 measurement should be carried out to further investigate the potential of this molecule as a biomarker of cholangiocarcinoma.

Author studied 64 patients with chronic biliary pancreatitis and obesity. In most cases the observed patients had also a diagnosis of non-alcoholic steatohepatitis. It was shown that in combined pathology there were revealed atherogenic blood lipid profile, disorders of liver functional state, sonographic changes of pancreas, liver, and gallbladder. Inclusion of multinutrient functional complexes "Grinization" in complex therapy improved sonography results, blood lipid levels, and eliminated biochemical manifestations of hepatocytes' cytolysis and cholestasis.

Blood oxygen transport and oxygen extraction were assessed in horses with colic. A gravity score (GS) ranging from 1 to 3 was attributed to each colic case with healthy horses used as controls. Jugular venous and carotid arterial blood samples were collected and concentrations of 2,3-diphosphoglycerate, adenosine triphosphate, inorganic phosphate and chloride were determined. pH and partial pressures of carbon dioxide (PCO(2)), and oxygen (PO(2)) were also measured. Oxygen equilibrium curves (OEC) were constructed under standard conditions and oxygen extraction ratios calculated. Haemoglobin oxygen affinity measured under standard conditions (P50(std)) was unchanged in colic horses compared with healthy controls. Horses with the highest GS, i.e. 3 had lower blood pH values than healthy animals. Arterial and venous partial pressures of oxygen at 50% haemoglobin saturation (P50(a) and P50(v)) were significantly higher in horses suffering from colic (GS=3) than in healthy horses. The oxygen extraction ratio was also significantly increased in colic horses with a GS of 3. A rise in the oxygen extraction ratio detected in the most severely affected animals seemed to reflect the compensatory properties of the oxygen transport system where extraction of oxygen from the blood increases when systemic oxygen delivery decreases, as might be anticipated in horses with colic.

Background: Biliary bacteria are more common in elderly patients and cause more serious illnesses. The reasons for this are unclear. We noted previously that bacterial serum-sensitivity and induction of TNFalpha production in sera (iTNFsera) were associated with severe biliary infections. We examined the influence of age and these factors on illness severity., Methods: Three-hundred and forty patients were studied. Gallstones and bile were cultured. Illness was staged as none (no clinical infection or inflammation), SIRS (fever, leukocytosis), severe (cholangitis, abscess, empyema), or MODS (bacteremia, hypotension, organ dysfunction/failure). Bacterial serum-sensitivity and TNFalpha induction were measured. Younger (< 70 years) and elderly (> or = 70 years) patients were compared., Results: Biliary bacteria were more common in elderly (64% vs 41%, P < .0001). Among patients with biliary bacteria, the elderly had more serious illnesses: none: 44% younger, 19% elderly; SIRS: 16% younger, 22% elderly; severe: 22% younger, 21% elderly; MODS 18% younger, 38% elderly (P = .003). Bacteria from elderly patients induced more TNFalpha (580 vs 310 pg/ml, P = .023). In both groups, serum-sensitive bacteria caused infectious manifestations and induced abundant TNFalpha; however, serum-resistant bacteria from elderly usually (69%) caused infectious manifestations and abundant TNFalpha, while serum-resistant bacteria from younger patients rarely (8%) caused infectious manifestations and minimal TNFalpha. Elderly patients with high iTNFsera bacteria had more severe illnesses., Conclusions: Biliary bacteria were more common in elderly patients and produced more serious illnesses. Many younger patients with biliary bacteria displayed no infectious manifestations. Elderly patients harbored more virulent bacteria, and had a heightened response to high iTNFsera bacteria, as well as bacteria largely tolerated by younger patients.

Objectives: Serum disialotransferrin is a specific marker of heavy alcohol consumption. We tested its accuracy and probability in detecting alcoholic cause of acute pancreatitis (AP)., Methods: Blood samples from 271 consecutive AP patients, admitted to the Helsinki University Central Hospital emergency unit, were analyzed., Results: The median (range) disialotransferrin value was significantly higher (P = 0.001) in AP patients with alcoholic (n = 172) 1.6% (0.3%-14.4) than with biliary (n = 60) 0.7% (0.3%-1.3%) or other causes (n = 39) 0.8% (0.3%-4.1%). In receiver operating curve analysis, disialotransferrin, as a single analyte, was significantly (P = 0.001-0.0001) more accurate (area under the curve [AUC], 0.88; 95% confidence interval [CI], 0.84-0.92) in detecting alcoholic AP as compared with glutamyl transferase (AUC, 0.51; 95% CI, 0.45-0.57), aspartate aminotransferase (AUC, 0.57; 95% CI, 0.51-0.63), alanine aminotransferase (AUC, 0.63; 95% CI, 0.57-0.69), erythrocyte mean cell volume (AUC, 0.72; 95% CI, 0.67-0.78), amylase (AUC, 0.74; 95% CI, 0.67-0.78), C-reactive protein (AUC, 0.65; 95% CI, 0.59-0.71), and bilirubin (AUC, 0.55; 95% CI, 0.49-0.62). At a disialotransferrin cutoff of 1.2%, giving an 8% false-positive rate, the positive likelihood ratio was 8.47. Thus, a positive disialotransferrin test result, performed within 24 hours of admission, increased the probability of alcoholic AP from pretest 64% to posttest 94%., Conclusions: Disialotransferrin, determined by capillary electrophoresis, is accurate, simple, and a rapid single biomarker of the alcoholic cause of AP.

Objective: To determine the diagnostic value of protein C (PC) for detecting hepatobiliary disease and portosystemic shunting (PSS) in dogs., Design: Prospective study., Animals: 238 clinically ill dogs with (n = 207) and without (31) hepatobiliary disease, including 105 with and 102 without PSS., Procedures: Enrollment required routine hematologic, serum biochemical, and urine tests; measurement of PC activity; and a definitive diagnosis. Total serum bile acids (TSBA) concentration and coagulation status, including antithrombin activity, were determined in most dogs. Dogs were grouped into hepatobiliary and PSS categories. Specificity and sensitivity were calculated by use of a PC cutoff value of 70% activity., Results: Specificity for PC activity and TSBA concentrations was similar (76% and 78%, respectively). Best overall sensitivity was detected with TSBA, but PC activity had high sensitivity for detecting PSS and hepatic failure. Protein C activity in microvascular dysplasia (MVD; PC > or = 70% in 95% of dogs) helped differentiate MVD from portosystemic vascular anomalies (PSVA; PC < 70% in 88% of dogs). A receiver operating characteristic curve (PSVA vs MVD) validated a useful cutoff value of < 70% activity for PC., Conclusions and Clinical Relevance: Combining PC with routine tests improved recognition of PSS, hepatic failure, and severe hepatobiliary disease and signified a grave prognosis when coupled with hyperbilirubinemia and low antithrombin activity in hepatic failure. Protein C activity can help prioritize tests used to distinguish PSVA from MVD and sensitively reflects improved hepatic-portal perfusion after PSVA ligation.

Background: Recently, it has been reported that the serum concentration of IgG4, a minor component of IgG subclasses, is increased in autoimmune pancreatitis. However, data regarding IgG4 concentrations in other pancreatic or biliary diseases have been insufficient., Methods: Serum IgG4 was measured in 116 patients with pancreatic or biliary diseases (35 autoimmune pancreatitis, 24 chronic pancreatitis except autoimmune pancreatitis, 11 primary sclerosing cholangitis, 23 pancreatic cancer, 3 islet cell tumor, 2 papilla cancer, 15 bile duct cancer, and 3 gallbladder cancer patients). The cut-off concentration of IgG4 was 135 mg/dl., Results: Increased serum IgG4 was observed in 33 of 35 patients with autoimmune pancreatitis, 0 of 24 with chronic pancreatitis, 4 of 11 with primary sclerosing cholangitis, 0 of 23 with pancreatic cancer, 0 of 3 with islet cell tumor, 0 of 2 with duodenal papilla cancer, 0 of 15 with bile duct cancer and 0 of 3 with gallbladder cancer patients., Conclusions: Serum IgG4 was increased in autoimmune pancreatitis and was within normal limits for other pancreatic or biliary diseases except primary sclerosing cholangitis.

Aim: To determine characteristics of a cytokine status in chronic pancreatitis (CP) depending on etiological factor, stage of the disease, complications, therapy. Material and methods. 72 patients had chronic alcoholic pancreatitis (CAP), 38 patients--chronic biliary pancreatitis (CBP). Control group consisted of 20 healthy subjects., Results: At early stages and height of CAP exacerbation, concentrations of IL-1beta, IL-6, IL-8, TNF-gamma and TNFalpha were elevated (951.1 +/- 104.2 pg/ml; 172.8 +/- 24.3 pg/ml; 432.6 +/- 68.5 pg/ml; 823.3 +/- 97.5 pg/ml; 158.7 +/- 19.6 pg/ml, respectively). Regenerative processes in CP were accompanied with IL-4 elevation to 614.9 +/- 64.6 pg/ml. In CAP without complications and with them the levels of cytokines differed significantly. The level of TGF-beta1 stimulating development of fibrosis was in CAP patients 627.8 +/- 92.2 pg/ml, in CAP patients with complications--796.8 +/- 102.5, in the controls--40.2 +/- 4.6 pg/ml (p < 0.05). In early stages of CBP exacerbation, IL-1beta rose to 527.2 +/- 62.7 pg/ml, IL-6--to 80.9 +/- 11.4 pg/ml, IL-8--to 290.4 +/- 46.8 pg/ml, INF-gamma to 853.3 +/- 91.6 pg/ml; TNF-alpha--to 79.7 +/- 8.3 pg/ml, TGF-beta1--534.1 +/- 78.4 pg/ml. With attenuation of acute syndromes and development ofregeneration, levels of IL-4 went up (226.7 +/- 32.4 pg/ml)., Conclusion: CP is accompanied by increase in cytokine contents depending on the etiological factor, variants of course, stage, presence of complications.

Purpose: Opinions about early endoscopic sphincterotomy and time of laparoscopic cholecystectomy in acute biliary pancreatitis are still controversial. Some authors reserved this procedure only for cases in which the stones were visualized during ERCP or patients had clinical symptoms of acute cholangitis. The aim was the assessment of the dynamic of changes of proinflammatory cytokines and white blood cells in time in patients with acute biliary pancreatitis after performed endoscopic sphincterotomy and laparoscopic cholecystectomy., Material and Methods: We enrolled 43 consecutive patients with clinically diagnosed mild forms of acute biliary pancreatitis. All were treated by early endoscopic sphincterotomy and laparoscopic cholecystectomy performed during the first 48 hours after admission. The course of the disease was monitored by measurement of the level of proinflammatory cytokines., Results: Marked decrease of the level of proinflammatory interleukins within 24 hours after endoscopic sphincterotomy was observed. Mean values of IL-6 and IL-8 were statistically lower immidiately after this procedure (p < 0.001). Subsequent decrease was achieved after laparoscopic cholecystectomy. The mean values of TNF-alpha and IL-12p40 were relatively constant throughout the study period., Conclusion: All patients suffering from mild acute biliary pancreatitis should be treated by using minimally invasive procedures. However, such a only treatment should be reserved for experienced centers.

Enteric fever due to Salmonella Typhi is a major public health problem. Typhoid carriers have high titres of Vi agglutinins in their sera. We worked out the baseline data for Vi agglutinins from 705 healthy blood donors (controls) by ELISA and compared it with 446 patients with biliary, gastrointestinal and other related diseases (cases). The samples were divided into five groups based on the disease condition of the patients from whom they were collected. Group A (n=196) consisted of patients with stones in the gall bladder/common bile duct and Group B (n=27) with gall bladder carcinoma. Group C (n=33) comprised patients with carcinoma of the pancreas/ampulla, obstructive jaundice and/or cholangiocarcinoma. Group D (n=112) had patients with acute/chronic pancreatitis, abdominal pain, intestinal obstruction, peritonitis, carcinoma oesophagus, chronic diarrhoea, gastrointestinal bleeding and dyspepsia. Group E (n=78) included patients with miscellaneous diseases. The mean absorbance value obtained for healthy subjects +3 standard deviations was taken as the cut-off value for a positive typhoid carrier. In Group A, 10.2% samples were positive; in Group B, 7.4%; in Group C, 12.0%; in Group D, 9.8% and in Group E, 9.0%. There was a highly significant (P <0.001) increase in the presence of Vi agglutinins in the cases compared to the controls. High prevalence of typhoid carriers occurs in patients with biliary, gastrointestinal and other related diseases. Vi serology employing highly purified Vi antigen offers a practical and cost-effective way of screening for S. Typhi carriers.