Changes in beta-catenin expression and activation during progression of primary sclerosing cholangitis predict disease recurrence

Primary sclerosing cholangitis (PSC) is a rare, chronic, cholestatic liver disease characterized by progressive inflammation and fibrosis of the bile ducts. We have previously demonstrated the importance of Wnt/β-catenin signaling in mouse models of PSC. In this study, we wished to determine the clinical relevance of β-catenin localization in patient samples. In livers explanted from patients diagnosed with PSC, the majority (12/16; 75%) lacked β-catenin protein expression. Biopsies from patients post-transplant were classified as recurrent or non-recurrent based on pathology reports and then scored for β-catenin activation as a function of immunohistochemical localization. Despite lack of statistical significance, patients with recurrent primary disease (n = 11) had a greater percentage of samples with nuclear, transcriptionally active β-catenin (average 58.8%) than those with no recurrence (n = 10; 40.53%), while non-recurrence is correlated with β-catenin staining at the cell surface (average 52.63% for non-recurrent vs. 27.34% for recurrent), as determined by three different methods of analysis. β-catenin score and years-to-endpoint are both strongly associated with recurrence status (p = 0.017 and p = 0.00063, respectively). Finally, there was significant association between higher β-catenin score and increased alkaline phosphatase, a marker of biliary injury and disease progression. Thus, β-catenin expression and activation changes during the progression of PSC, and its localization may be a useful prognostic tool for predicting recurrence of this disease.

A critical analysis of the ten-year experience of using endoscopic transpapillary interventions in an urgent surgical hospital

The aim of this work was to provide a critical analysis of the ten-year experience of using transpapillary interventions in an urgent surgical hospital with a detailed study of all groups of registered complications.Material and methods. In the period from 2008 to 2018, 1188 retrograde endoscopic transpapillary grafts were performed on the bile ducts with dissection of the major duodenal papilla in a typical and atypical way on the basis of our clinic. The group of observed patients included 1188 patients with endoscopic papillosphincterotomy, including 839 women (70.6%) and 349 men (29.4%). The average age was 63.2 ± 1.25.Results. During the period, 25 complications (2.1%) were revealed when performing transpapillary interventions with dissection of the major duodenal papilla: acute pancreatitis — 10 patients (0.8%); bleeding from the opening of the major duodenal papilla — 4 (0.33%), perforation 12p. intestines — 4 (0.33%), breakage of the basket cable with wedging — 1 (0.08%), cholangitis — 1 (0.08%), overlapping with a stent of the lobar duct — 1 (0.08%). The overall mortality associated with complications is 0.25%. Based on the analyzed material, the iatrogenic index was calculated. It was 0.044. After the analysis of complications, on the basis of the data obtained, we proposed an algorithm of actions when performing transpapillary interventions.Conclusion. Based on the study, we come to the conclusion that it will not be possible to completely level the risk and avoid possible papillotomic-induced complications. In this regard, the early, preferably intraoperative diagnosis of the latter and the prompt implementation of correlating therapeutic measures are of great importance, which will undoubtedly improve the treatment results and have a positive eff ect on the outcome of the disease.

WAYS TO IMPROVE THE RESULTS OF TREATMENT OF PATIENTS WITH CHOLELITHIASIS AND MECHANICAL JAUNDICE.

Purpose. To create a personalized tactic of surgical treatment of patients with BSD and MJ considering the stage of the pathological process and thereby improve the results of treatment. Materials and methods. The experience of diagnosis and treatment of 537 patients with complications of cholelithiasis, manifested by mechanical jaundice, was analyzed. The first stage was 537 minimally invasive decompressions of the biliary tract, the second-500 different types of endosurgical interventions. Results. Depending on the tactical principles, all the subjects were divided into two groups. In one (control) group (n = 249), patients were admitted from 2010 to 2014. Their treatment was empirical: decompression of the bile tree was performed at different times, and surgery was performed without taking into account the stages of the pathological process and the severity of the patients. In the other analyzed group (n = 251), patients were admitted to the hospital from 2015 to 2019. Their treatment tactics were personalized: taking into account the stages of mechanical jaundice. individual terms of decompression of the bile ducts and the choice of surgical intervention were determined. When comparing the results obtained, the advantage of the personalized approach was established: a decrease in the percentage of postoperative complications and mortality was revealed. Conclusion. In patients with cholelithiasis and jaundice, the severity of the condition is due to hyperbilirubinemia. Stage 2 of mechanical jaundice-determined by the severity of cytolysis in hepatic insufficiency, manifested by hypertransaminasemia. The severity of cholangitis is determined by purulent-inflammatory, as well as septic signs of the disease, characterized by leukocytosis, circulating immune complexes and medium-weight molecules. In the cholestatic stage of jaundice development, treatment is planned, in the cytolytic stage — urgent, and in cholangitis-emergency. The use of personalized tactics for the treatment of patients with breast cancer has reduced the number of complications and mortality.

AUTOIMMUNE CHOLESTATIC LESIONS OF BILIARY DUCTS

The review presents literature data and original findings of light and electron microscopy of pathomorphological changes in the bile ducts in primary sclerosing cholangitis (PSC), immunoglobulin G4 (IgG4)-associated autoimmune sclerosing cholangitis and overlap syndromes: PSC + chronic autoimmune hepatitis (AIH); PSC + primary biliary cirrhosis (PBC).

Professor Volodymyr Zemskov — a world-renowned Ukrainian surgeon

The article describes the professional and scientific way of professor Volodymyr Serhiyovych Zemskov, a prominent Ukrainian surgeon and a founder of the Kyiv Center for Liver, Bile Ducts and Pancreas Surgery which is currently based in the Kyiv City Clinical Hospital No10. The article presents the memories of his students and contemporaries, the facts about his professional biography and career development. The paper describes the main scientific interests of Volodymyr Zemskov, his achievements and scientific work.

Efemp1 modulates elastic fiber formation and mechanics of the extrahepatic bile duct

EGF-Containing Fibulin Extracellular Matrix Protein 1 (EFEMP1, also called fibulin 3) is an extracellular matrix protein linked in a genome-wide association study to biliary atresia, a fibro-inflammatory disease of the neonatal extrahepatic bile duct. EFEMP1 is expressed in most tissues and Efemp1 null mice have decreased elastic fibers in visceral fascia; however, in contrast to other short fibulins (fibulins 4 and 5), EFEMP1 does not have a role in the development of large elastic fibers, and its overall function remains unclear. We demonstrated that EFEMP1 is expressed in the submucosa of both neonatal and adult mouse and human extrahepatic bile ducts and that, in adult Efemp1+/- mice, elastin organization into fibers is decreased. We used pressure myography, a technique developed to study the mechanics of the vasculature, to show that Efemp1+/- extrahepatic bile ducts are more compliant to luminal pressure, leading to increased circumferential stretch. We conclude that EFEMP1 has an important role in the formation of elastic fibers and mechanical properties of the extrahepatic bile duct. These data suggest that altered expression of EFEMP1 in the extrahepatic bile duct leads to an abnormal response to mechanical stress such as obstruction, potentially explaining the role of EFEMP1 in biliary atresia.

Progress and Current Limitations of Materials for Artificial Bile Duct Engineering

Bile duct injury (BDI) and bile tract diseases are regarded as prominent challenges in hepatobiliary surgery due to the risk of severe complications. Hepatobiliary, pancreatic, and gastrointestinal surgery can inadvertently cause iatrogenic BDI. The commonly utilized clinical treatment of BDI is biliary-enteric anastomosis. However, removal of the Oddi sphincter, which serves as a valve control over the unidirectional flow of bile to the intestine, can result in complications such as reflux cholangitis, restenosis of the bile duct, and cholangiocarcinoma. Tissue engineering and biomaterials offer alternative approaches for BDI treatment. Reconstruction of mechanically functional and biomimetic structures to replace bile ducts aims to promote the ingrowth of bile duct cells and realize tissue regeneration of bile ducts. Current research on artificial bile ducts has remained within preclinical animal model experiments. As more research shows artificial bile duct replacements achieving effective mechanical and functional prevention of biliary peritonitis caused by bile leakage or obstructive jaundice after bile duct reconstruction, clinical translation of tissue-engineered bile ducts has become a theoretical possibility. This literature review provides a comprehensive collection of published works in relation to three tissue engineering approaches for biomimetic bile duct construction: mechanical support from scaffold materials, cell seeding methods, and the incorporation of biologically active factors to identify the advancements and current limitations of materials and methods for the development of effective artificial bile ducts that promote tissue regeneration.

Resection of extrahepatic bile ducts with partial hepatectomy for treating intra- and extrahepatic hepatolithiasis

Background To evaluate the efficacy and safety of our new surgical procedures for primary intra- and extrahepatic hepatolithiasis. Hepatolithiasis is an intractable disease with frequent recurrences. Methods From 1996 to 2005, 142 patients with intrahepatic and/or extrahepatic hepatolithiasis treated with the conventional surgical methods were included as the control group, while 128 consecutive patients treated with new surgical methods from 2006 to 2015 were included as the observation group. The new surgical procedures included a comprehensive intraoperative exploration of the bile ducts, focusing on the structure and function of the hilar bile duct and duodenal papilla, exploration of the affected liver, and bile culture. Results The observation group had a significantly higher complete stone clearance rate than the control group (100% vs. 65.96%). The observation group had significantly lower incidences of cholangitis and bile duct stones, as well as a higher excellent and good long-term surgical efficacy rate (86.24% vs. 52.73%). Multivariate Cox analysis showed that the control group had a higher risk for fair + poor efficacy than the observation group (HR: 8.47). Conclusions Our new surgical procedures are safe and can provide a good long-term efficacy for treating primary hepatolithiasis intra- and extrahepatic hepatolithiasis.

Interventional radiology techniques in the treatment of cholangiolithiasis: indications, efficacy, accessibility

Our days, the problem of treating complicated forms of cholelithiasis continues to be relevant despite the undoubted successes in the field of hepatobiliary surgery. Cholangiolithiasis is one of the most frequent and dangerous complications of cholelithiasis, it is detected in 8–26 % of patients with cholelithiasis. In some cases, it is impossible to perform an endoscopic retrograde method, these special situations require the development of new original minimally invasive methods for resolving cholangiolithiasis, which have all the advantages of «small access». The analysis of the treatment of 466 operated patients with cholelithiasis complicated by cholangiolithiasis and mechanical jaundice in the period from 2013 to 2019 was carried out. The patients were divided into 3 groups: 1 — the endoscopic retrograde method was used (n = 369), 2 — laparotomic access (n = 26), 3 — antegrade X-ray interventional method (n = 71). The results obtained allow us to conclude that the antegrade interventional radiology technique for the treatment of choledocholithiasis has a high clinical efficacy comparable to the endoscopic technique. The use of this treatment option avoids traumatic laparotomies and open interventions on the bile ducts. The use of method is justified in cases of impossibility of performing endoscopic intervention, or its ineffectiveness.