This document presents a comprehensive overview of the management of postinflammatory pancreatic and peripancreatic fluid collections, with a particular emphasis on endoscopic treatment, developed by a team of experts based on the latest clinical and scientific evidence. The guidelines present a detailed scheme of treatment of patients with local complications of acute pancreatitis in the form of postinflammatory pancreatic and peripancreatic fluid collections.

Background: Glycoprotein-2 (GP2) IgA is a predictor of disease severity in primary sclerosing cholangitis (PSC). We examined GP2 ' s occurrence in the biliary tract, the site of inflammation. Methods: GP2 was analyzed using ELISA, immunoblotting, mass spectrometry, and immunohistochemistry. The samples included: 20 bile and 30 serum samples from PSC patients, 23 bile and 11 serum samples from patients with gallstone disease (GD), 15 bile samples from healthy individuals undergoing liver-donation surgery (HILD), 20 extracts of gallstones (GE) obtained during cholecystectomy, and 101 blood-donor sera. Results: Biliary GP2 concentrations were significantly higher in patients with PSC and GD than in HILD (p < 0.0001). Serum GP2 levels were similar in PSC and GD patients, and controls, but lower than in bile (p < 0.0001). GP2 was detected in all 20 GEs. Mass spectrometry identified GP2 in the bile of 2 randomly selected GD and 2 PSC patients, and in none of 2 HILD samples. GP2 was found in peribiliary glands in 8 out of 12 PSC patients, showing morphological changes in acinar cells, but not in GD-gallbladders. Conclusions: GP2 is present in bile of PSC and GD patients. It is synthesized in the peribiliary glands of PSC patients, supporting a pathogenic role for biliary GP2 in PSC.

Introduction: Endosonography-guided biliary drainage (EUS-BD) serves as a rescue treatment modality for patients with malignant biliary obstruction when endoscopic retrograde cholangiopancreatography (ERCP) fails. Objectives: This study explores the effects of EUS-BD on liver function and quality of life (QoL). Patients and Methods: Patients with malignant biliary obstruction and failed ERCP were enrolled to undergo EUS-BD. QoL, including pruritus severity, was evaluated using EQ-5D-5L and PSS-10 questionnaires before and after EUS-BD. Serum bilirubin and liver function tests were measured on the procedure day, two days, and at least 14 days post-procedure. Results: During a 20-month study period, 1755 ERCPs were performed, with 595 for malignant cases. Of these, 49 underwent EUS-BD following failed ERCP, and 37 (54% women, age range 34-87 years) completed the 14-day follow-up. Pancreatic cancer was the most common (49%) condition, and the median hospital stay was 4 days. Serum bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyl transferase significantly decreased 2 and 14 days after EUS-BD (all p < 0.001). Pruritus significantly improved, with an average reduction of 5.19 points on the PSS-10 scale two weeks post-procedure (p < 0.001). EUS-BD led to improvements in anxiety and depression according to the EQ-5D-5L (p = 0.013). Conversely, deteriorations were observed in the Mobility, Self-Care, and Usual Activities domains over time (all p < 0.05). Successful EUS-BD enabled the resumption of chemotherapy in 11 (30%) patients. The median post-procedure survival was 112 (range 27-1030) days. Conclusions: EUS-BD improves liver parameters and some aspects of life quality in patients with malignant biliary obstruction, thereby increasing their eligibility for optimal palliative care.

This study examined the interfacial evolution of individual bile salts (BSs) and their blends with phosphatidylcholine (BS/PC) to simulate the complex behaviour of human bile (HB) during lipolysis at the triglyceride/water interface. Using adsorption and desorption cycles, mimicking exposure to small intestinal fluids, we demonstrate that the interfacial behaviour of real HB can be replicated using simple mixtures of BSs and PC. Interfacial tension (IFT) measurements after lipolysis and desorption showed no significant differences (P > 0.05) between HB samples and BS/PC mixtures across the total BS concentrations analysed (2.23-7.81 mM). However, individual BSs without PC yielded significantly different IFT results (P < 0.01) compared to HB, highlighting the importance of phospholipids. Dilatation rheology further emphasised the need for accurate phospholipid representation in bile models. Our results suggest that phospholipids in HB and in BS/PC systems enhance resistance to desorption, potentially affecting lipolysis. This is important, as current in vitro digestion models often replicate only intestinal BS concentrations to mimic the behaviour of HB in the intestinal lumen. Furthermore, the specific composition of BSs in HB appears less critical than the overall BS and phospholipid contents, suggesting that the kinetics of triglyceride digestion is influenced by the combined luminal concentrations of these components. These findings have significant implications for understanding the role of bile in digestion and offer insights for designing more accurate in vitro models to study the gastrointestinal behaviour of food emulsions and lipid-based delivery systems.

1) Department of Gastroenterology and Hepatology with Internal Disease Unit, Teaching Hospital No 1 in Rzeszów, Rzeszów, Poland; 2) Medical Department, University of Rzeszów, Rzeszów, Poland; 3) Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany; 4) Laboratory of Metabolic Liver Diseases, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland IMAGE OF THE ISSUE DOI: http://dx.doi.org/10.15403/jgld-4110

Objectives Endoscopic biliary drainage is a first-line treatment in patients with unresectable malignant biliary obstruction. In most cases the drainage is conducted using endoscopic retrograde cholangiopancreatography (ERCP). Percutaneous transhepatic biliary drainage or endosonography-guided biliary drainage (EUS-BD) represents therapeutic options after unsuccessful ERCP. Here we report on 2 years experience in the management of patients diagnosed with malignant biliary obstruction using EUS-BD. Methods Retrospective data were collected on patients who underwent EUS-BD due to malignant biliary obstruction at our centre between April 2016 and April 2018. Only patients who had two unsuccessful attempts of ERCP prior to EUS-BD were included. We analysed the technical success (ie, creation of anastomosis and successful placement of a stent) and complication rate of EUS-BD, and monitored changes in serum bilirubin and liver function tests after 2 days, and at least 2 weeks, following the procedure. Results Screening of 1781 ERCP procedures performed in our department during the inclusion period led to the identification of 31 patients (18 women, age range 51–92 years, 58% with pancreatic cancer) who fulfilled the inclusion criteria. Hepaticogastrostomy and choledochoduodenostomy were performed in 12 and 19 patients, respectively. The technical success rate was 97% and the complication rate was 12.9%. EUS-BD resulted in a significant decrease in serum bilirubin (p<0.01). Conclusions EUS-BD represents a reasonable therapeutic option after unsuccessful ERCP in patients with malignant biliary obstruction. Possible complications have to be kept in mind and this procedure should be performed at centres experienced in ERCP and EUS.

Abstract Iron deficiency is the most common mammalian nutritional deficiency during the neonatal period. However, among mammalian species neonatal iron deficiency anemia (IDA), the most severe consequence of iron scarcity, occurs regularly in pigs. Although intramuscular supplementation of piglets with high amounts of iron dextran (FeDex) is largely considered an appropriate preventive therapy for IDA prophylaxis, an increasing evidence shows that it negatively affects pig physiology. The aim of our study was to evaluate the efficacy of non-invasive supplementation of piglets with sucrosomial ferric pyrophosphate (SFP), a highly bioavailable dietary iron supplement in preventing IDA, in humans and mice. Results of our study show that SFP given to piglets per os in the amount of 6 mg Fe daily efficiently counteracts IDA at a rate comparable with the traditional FeDex-based supplementation (100 mgFe/kG b.w.; i.m. injection). This was indicated by physiological values of red blood cell indices and plasma iron parameters measured in 28-day old piglets. Moreover, SFP-supplemented piglets showed significantly lower (P ≤0.05) plasma level of 8-isoprostane, a biomarker for oxidative stress compared to FeDex-treated animals, implying lesser toxicity of this order of iron replenishment. Finally, supplementation with SFP does not increase considerably the blood plasma hepcidin, a peptide that acts to inhibit iron absorption from the diet. SFP emerges as a promising nutritional iron supplement, with a high potential to be adopted in the postnatal period.

The gastrointestinal hydrolysis of food proteins has been portrayed in scientific literature to predominantly depend on the activity and specificity of proteolytic enzymes. Human bile has not been considered to facilitate proteolysis in the small intestine, but rather to assist in intestinal lipolysis. However, human bile can potentially influence proteins that are largely resistant to gastric digestion, and which are mainly hydrolysed after they have been transferred to the small intestine. We used purified and food-grade bovine milk β-lactoglobulin (βLg) to assess the impact of bile salts (BS) on the in vitro gastrointestinal digestion of this protein. Quantitative analysis showed that the proteolysis rate increased significantly with increasing BS concentration. The effect was consistent regardless of whether individual BS or real human bile samples, varying in BS concentrations, were used. The total BS content of bile was more important than its BS composition in facilitating the proteolysis of βlg. We also show that the impact of human bile observed during the digestion of purified βLg and βLg-rich whey protein isolate can be closely replicated by the use of individual BS mixed with phosphatidylcholine. This could validate simple BS/phosphatidylcholine mixtures as human-relevant substitutes of difficult-to-obtain human bile for in vitro proteolysis studies.

Determination of the cause of a biliary obstruction is often inconclusive from serum analysis alone without further clinical tests. To this end, serum markers as well as the composition of bile of 74 patients with biliary obstructions were determined to improve the diagnoses. The samples were collected from the patients during an endoscopic retrograde cholangiopancreatography (ERCP). The concentration of eight bile salts, specifically sodium cholate, sodium glycocholate, sodium taurocholate, sodium glycodeoxycholate, sodium chenodeoxycholate, sodium glycochenodeoxycholate, sodium taurodeoxycholate, and sodium taurochenodeoxycholate as well as bile cholesterol were determined by HPLC-MS. Serum alanine aminotransferase (ALT), aspartate transaminase (AST), and bilirubin were measured before the ERCP. The aim was to determine a diagnostic factor and gain insights into the influence of serum bilirubin as well as bile salts on diseases. Ratios of conjugated/unconjugated, primary/secondary, and taurine/glycine conjugated bile salts were determined to facilitate the comparison to literature data. Receiver operating characteristic (ROC) curves were determined, and the cut-off values were calculated by determining the point closest to (0,1). It was found that serum bilirubin was a good indicator of the type of biliary obstruction; it was able to differentiate between benign obstructions such as choledocholithiasis (at the concentration of >11 µmol/L) and malignant changes such as pancreatic neoplasms or cholangiocarcinoma (at the concentration of >59 µmol/L). In addition, it was shown that conjugated/unconjugated bile salts confirm the presence of an obstruction. With lower levels of conjugated/unconjugated bile salts the possibility for inflammation and, thus, neoplasms increase.

The demand for iron is high in pregnancy to meet the increased requirements for erythropoiesis. Even pregnant females with initially iron-replete stores develop iron-deficiency anemia, due to inadequate iron absorption. In anemic females, the maternal iron supply is dedicated to maintaining iron metabolism in the fetus and placenta. Here, using a mouse model of iron deficiency in pregnancy, we show that iron recycled from senescent erythrocytes becomes a predominant source of this microelement that can be transferred to the placenta in females with depleted iron stores. Ferroportin is a key protein in the molecular machinery of cellular iron egress. We demonstrate that under iron deficiency in pregnancy, levels of ferroportin are greatly reduced in the duodenum, placenta and fetal liver, but not in maternal liver macrophages and in the spleen. Although low expression of both maternal and fetal hepcidin predicted ferroportin up-regulation in examined locations, its final expression level was very likely correlated with tissue iron status. Our results argue that iron released into the circulation of anemic females is taken up by the placenta, as evidenced by high expression of iron importers on syncytiotrophoblasts. Then, a substantial decrease in levels of ferroportin on the basolateral side of syncytiotrophoblasts, may be responsible for the reduced transfer of iron to the fetus. As attested by the lowest decrease in iron content among analyzed tissues, some part is retained in the placenta. These findings confirm the key role played by ferroportin in tuning iron turnover in iron-deficient pregnant mouse females and their fetuses.

The gastrointestinal mucus layer represents the last barrier between ingested food or orally administered pharmaceuticals and the mucosal epithelium. This complex gel structure plays an important role in the process of small intestinal absorption. It provides protection against hazardous particles such as bacteria but allows the passage of nutrients and drug molecules towards the intestinal epithelium. In scientific research, mucus from animal sources is usually used to simulate difficult-to-obtain human small intestinal mucus for investigating the intramucus transport of drug delivery systems or food nanoparticles. However, there is a lack of evidence the human mucus can be reliably substituted by animal counterparts for human-relevant transport models. In this report, a procedure for collecting human mucus has been described. More importantly, the permeability characteristics of human and porcine small intestinal mucus secretions to sub-micron sized particles have been compared under simulated intestinal conditions. Negatively charged, 500 nm latex beads were used in multiple-particle tracking experiments to examine the heterogeneity and penetrability of mucus from different sources. Diffusion of the probe particles in adult human ileal mucus and adult pig jejunal and ileal mucus revealed no significant differences in microstructural organisation or microviscosity between the three mucus types ( P > 0.05). In contrast to this interspecies similarity, the intraspecies comparison of particle diffusivity in the mucus obtained from adult pigs vs. 2-week old piglets showed better penetrability of the piglet mucus. The mean Stokes–Einstein viscosity of the piglet jejunal mucus was approx. two times lower than the viscosity of the pig jejunal mucus ( P < 0.05). All mucus structures were also visualised by scanning electron microscopy. This work validates the use of porcine small intestinal mucus collected from fully-grown pigs for studying colloidal transport of sub-micron sized particles in mucus under conditions mimicking the adult human small intestinal environment.

Small intestinal mucus transport of food-derived particulates has not been extensively studied, despite mucus being a barrier nutrients need to cross before absorption. We used complex dispersions of digesta obtained from simulated, dynamic gastrointestinal digestion of yogurt to examine the penetrability of human and porcine mucus to the particles formed of lipolysis products. Quantitative, time-lapse confocal microscopy revealed a sieve-like behaviour of the pig jejunal and ileal mucus. The digesta diffusivity decreased significantly over the first 30 min of mucus penetration, and then remained constant at ca. 5 x 10(-12) m(2) s(-1) (approx. 70% decrease from initial values). A non-significantly different penetrability was recorded for the ileal mucus of adult humans. The digesta diffusion rates in neonatal, jejunal mucus of 2 week old piglets were 5-8 times higher than in the three different types of adult mucus. This is the first report that validates the mucus of fully-grown pigs as a human-relevant substitute for mucus permeation studies of nutrients/bio-actives and/or complex colloidal dispersions (e.g., post-digestion food particulates, orally-administrated delivery systems).

Moderate intravascular hemolysis is a common condition in newborns. It is followed by the accumulation of bilirubin, which is a secondary product of the activity of heme oxygenase-1, an enzyme that catalyzes the breakdown of heme released from disrupted erythrocytes and taken up by hepatic macrophages. Although these cells are a major site of enzymatic heme breakdown in adults, we show here that epithelial cells of proximal tubules in the kidneys perform the functions of both heme uptake and catabolism in mouse neonates. A time-course study examining mouse pups during the neonatal period showed a gradual recovery from hemolysis, and concomitant decreases in the expression of heme-related genes and non-heme iron transporters in the proximal tubules. By adjusting the expression of iron-handling proteins in response to the disappearance of hemolysis in mouse neonates, the kidneys may play a role in the detoxification of iron and contribute to its recirculation from the primary urine to the blood.

Endoscopic retrograde cholangiography (ERC) in patients with obstructive jaundice is unsuccessful in 3–12% of cases [ 1 Baniya R. Upadhaya S. Madala S. Subedi S.C. Shaik Mohammed T. Bachuwa G. Endoscopic ultrasound-guided biliary drainage versus percutaneous transhepatic biliary drainage after failed endoscopic retrograde cholangiopancreatography: a meta-analysis. Clin Exp Gastroenterol. 2017; 10: 67-74 Crossref PubMed Scopus (30) Google Scholar , 2 Bhutani M.S. Arora A. New developments in endoscopic ultrasound-guided therapies. Endoscopic Ultrasound. 2015; 4: 304-311 Crossref PubMed Scopus (9) Google Scholar ]. Such cases are usually managed with percutaneous transhepatic biliary drainage (PTCD) or surgery. Endoscopic ultrasound guided biliary drainage (EUS-BD) represents an alternative intervention for internal biliary drainage in experienced centres [ [3] Siddiqui U.D. Levy M.J. EUS-guided transluminal interventions. Gastroenterology. 2018; (pii: S0016-5085(18)30223-3)https://doi.org/10.1053/j.gastro.2017.12.046 Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar ]. Available comparative data suggest that EUS guided biliary drainage provides similar technical and clinical success rate compared to percutaneous biliary drainage [ 1 Baniya R. Upadhaya S. Madala S. Subedi S.C. Shaik Mohammed T. Bachuwa G. Endoscopic ultrasound-guided biliary drainage versus percutaneous transhepatic biliary drainage after failed endoscopic retrograde cholangiopancreatography: a meta-analysis. Clin Exp Gastroenterol. 2017; 10: 67-74 Crossref PubMed Scopus (30) Google Scholar , 4 Artifon E.L. Aparicio D. Paione J.B. Lo S.K. Bordini A. Rabello C. et al. Biliary drainage in patients with unresectable, malignant obstruction where ERCP fails: endoscopic ultrasonography-guided choledochoduodenostomy versus percutaneous drainage. J Clin Gastroenterol. 2012; 46: 768-774 Crossref PubMed Scopus (155) Google Scholar ]. EUS-guided cholangiography might be also used as a ‘road map’ for the subsequent attempt of ERC.