Objective: to demonstrate the experience of unresectable hilar cholangiocarcinoma treatment using neoadjuvant therapy followed by liver transplantation (LT).

Materials and methods. From 2017 to 2021, six patients were included in the treatment protocol for unresectable Klatskin tumor followed by liver transplantation at Granov Russian Scientific Center for Radiology and Surgical Technology. The neoadjuvant therapy included endobiliary photodynamic therapy (PDT), as well as regional and systemic chemotherapy. Each method was used at least three times for 4 to 5 months with radiological evaluation and measurement of CA 19-9 levels. Patients were placed on the waiting list when the tumor marker reduced, or when there were no radiological signs of disease progression and there was no acute cholangitis. The recipients underwent laparoscopic abdominal revision for carcinomatosis and assessment of lymph nodes in the hepatoduodenal ligament with urgent morphological examination. Where there was no extrahepatic spread, LT was performed according to the classical technique with paracaval, para-aortic and hepatoduodenal lymphodissection, biliodigestive anastomosis by an isolated Roux loop of small intestine. The operation was performed in three patients, all of them were men aged 40 to 55 years (mean 48). The mean time from the start of treatment to transplantation was 9.3 months (range 6 to 14). Mean CA 19-9 level at the time of intervention was 81.3 IU/mL (8 to 212).

Results. In three patients, CA 19-9 levels more than doubled on average over four months despite treatment. According to data from computed tomography RECIST assessment, two of the patients showed disease progression. In one patient, carcinomatosis was detected by diagnostic laparoscopy. In three patients, CA 19-9 levels decreased more than fourfold. Two of these patients were radiologically confirmed to have the disease stabilized, and one had a partial response. One patient died from sepsis three years after transplantation as a result of secondary biliary cirrhosis and biliary abscesses without signs of progression. Two patients are still alive after 6 and 21 months without signs of tumor progression.

Conclusion. LT for unresectable Klatskin tumor is effective in controlling the bioactivity of the tumor through the use of neoadjuvant therapy

Primary biliary cholangitis (PBC) is an autoimmune liver disease resulting from the destruction and inflammation of intrahepatic bile ducts. This end-stage disease was once the most common cause of liver transplantation. The use of ursodeoxycholic and obeticholic acids as a first-line and second-line treatment, respectively, slows down the disease. However, treatment is not effective in about 40% of PBC patients, and the disease may progress to cirrhosis and end-stage liver disease. These patients undergo liver transplantation to save their lives. After surgery, recurrent PBC can develop in a milder form and rarely requires liver retransplantation.

This paper presents a brief outline of the history of transplantation service in the Republic of Uzbekistan, which originated at the country’s Center for Kidney Transplantation. The role played by outstanding scientists in Uzbekistan, their works and efforts towards the creation of a separate area of clinical and scientific medicine in Uzbekistan, are highlighted. Achievements by the research school of U.A. Aripov, Academician of the Academy of Sciences of the Republic of Uzbekistan, who performed the first successful kidney transplantation in 1972, are shown. The ups and downs of national transplantation nephrology, as well as the birth of a national school of kidney transplantation, domiciled at the Vakhidov Republican Specialized Scientific and Practical Medical Center of Surgery, headed by academician F.G. Nazirov, and giving a stimulus to the «second breath» of the national school of transplantology, is reflected. Separate attention is devoted to the actual problems of national transplantology, moral, ethical and regulatory issues that inevitably accompany this scientific and clinical direction are reflected. Kidney transplant outcomes in Uzbekistan are given, the prospects for further scientific and clinical directions are indicated.

The first successful kidney autotransplantation was performed in 1902. The technique has undergone several changes since then. The indications and surgical technique are presented in this literature review. Kidney autotransplantation is the treatment of choice for preserving renal function. Three clinical observations on the use of kidney autotransplantation in urological and oncological practice are described: a patient after iatrogenic ureteral injury and two patients with primary retroperitoneal tumor. Literature analysis and clinical observations from urological and oncological practice show that kidney autotransplantation could be safely used for strictly selected indications.

The success of pancreatic islet allotransplantation in the treatment of patients with a difficult-to-manage type 1 diabetes depends mainly on the quantity and quality of islets isolated from the pancreas of deceased donors using enzyme preparations, primarily collagenase. Numerous studies on improvement and standardization of islet isolation techniques have reached their limits in the last decade. This has made it impossible to further boost the number and quality of clinical transplants. Taking into account the negative impact of collagenase technique on the morphofunctional properties of isolated islets, this work has studied the possibility of enzyme-free isolation of islet tissue purified of exocrine ballast. Experiments using the pancreas of newborn and young rabbits showed that developing methodological approaches to obtaining islet-like cultures without the use of exogenous enzymes is feasible.

Objective: to study the induction of osteogenesis caused by introducing into the defect area broadly porous cryogenically structured 3D carriers, based on serum albumin and loaded with a bioregulator isolated from bovine serum on an experimental model of mandible defect in rabbits in vivo.

Materials and methods. Cryogenically structured sponges in the form of cylindrical specimens, 5 mm in diameter and 5 mm in height, prepared from bovine serum albumin, were used as the bioregulator carrier. The experimental laboratory animals were male Chinchilla rabbits, weighing 2–2.5 kg. Bone tissue was skeletonized under anesthesia (intramuscular anesthetic Zoletil 100) with a 3-cm incision in the angle of the mandible and a 5-mm-diameter cutter was used to create a 2–3-mm deep defect to install an appropriate-size albumin sponge. A total of 24 animals participated in the experiment. X-ray control of the defect area was performed in vivo on day 14 using PanExam+ (Kavo) device (20 m X-ray). Histological examination of tissues was carried out at day 30 after the defect using a light microscope.

Results. Experiments performed indicate an active restoration of bone tissue in the extensive defect area when using an albumin-based 3D carrier with the inclusion of a bioregulator as compared to the control experiments. There were osteointegrative and osteoinductive processes, almost complete decomposition (biodegradation) of albumin sponge with formation of islands of dense bone tissue with small foci of coarse fibrous tissue in the defect. This demonstrated good dynamics of recovery processes at this stage of healing.

Conclusion. Under the action of a serum bioregulator contained in an albumin-based sponge, the repair process leads to restoration of normal bone tissue without formation of bone callus and altered bone tissue different from the native one.

Introduction. Developing a tissue-engineered pancreatic construct (TEPC) involves a search for matrices/scaffolds capable of mimicking the structure and composition of the natural extracellular matrix (ECM), which is an important component of the tissue microenvironment. A cell-free, tissue-specific matrix obtained from pancreas decellularization seems to be the most suitable for creation of a TEPC. The choice of pancreatic tissue decellularization protocol should take into account the morphological characteristics of the original pancreas. Preservation of the architectonics and composition of the native tissue in the decellularized pancreas matrix (DPM), and the presence of native ECM components allow for creation of conditions for prolonged vital activity of functionally active islet (insulin-producing) cells when creating TEPC.

Objective: to determine the optimal parameters for decellularization of deceased donor pancreas with fibrosis, lipomatosis, and without pronounced signs of fibrosis and lipomatosis.

Materials and methods. We used the caudal part of the pancreas obtained after multiorgan procurement from deceased donors, which was unsuitable for transplantation. Tissue-specific matrix was obtained by a combination of physical and chemical methods of pancreatic decellularization. A freeze-thaw cycle protocol and two protocols using osmotic shock were used. Samples of initial pancreatic tissue and decellularized fragments were subjected to histological analysis.

Results. It was shown that a physico-chemical method with freeze-thaw cycles is suitable for effective pancreatic decellularization in severe lipomatosis; a physico-chemical method using osmotic shock, but different protocol variants, is suitable for pancreas with diffuse fibrosis and for pancreas without pronounced signs of fibrosis and lipomatosis.

Conclusion. For complete human pancreatic decellularization, the protocol should be correlated with histological features of the original tissue.

Cell death represents the most critical pathologic entity in liver disease, which dictates pathologic consequences such as inflammation, fibrosis, and cell transformation. We analyzed the conclusions of studies on the involvement of different types of programmed cell death (PCD) in the pathogenesis of liver diseases. Three main forms of PCD (autophagy, apoptosis, necrosis) and five additional, still insufficiently studied PCD – necroptosis, ferroptosis, pyroptosis, partanatosis and entosis – observed in the liver in various acute and chronic diseases are considered. The involvement of several PCD at once in the development of any one pathology and one type of PCD in different pathologies was established. This indicates the existence of cross-regulation of metabolism in the liver cells with different levels of damage in the formation of the main dominant type of PCD. Available results indicate the possibility of attenuation (correction) of functional and morphological manifestations of PCD in the organ by controlled blocking of effector-mediated PCD pathways, as well as targeted induction of autophagy, anti-apoptotic and anti-necrotic mechanisms in liver cells.

Introduction. The use of immunomodulators to regulate reparative processes in affected organs and tissues remains a pressing issue. Of greatest interest is liver regeneration after extended hepatic resection (EHR) in donors in right lobe living related donor liver transplantation. We propose a transdermal therapeutic system (TTS) with an immunomodulator to enhance the natural process of liver tissue regeneration. Objective: to study the effect of transdermal administration of immunomodulator sodium aminodihydrophthalazinedione on early recovery processes in the liver after EHR in in vivo experiments.

Materials and methods. Sodium aminodihydrophthalazinedione was used as an active substance in TTS in the form of powder for preparation of intramuscular injection solution (Galavit®, SELVIM LLC). An experimental EHR model was performed on 22 male Wistar rats weighing 350–380 g. After HER, all animals were divided into two groups. Group 1 (n = 10) consisted of untreated animals. In group 2 (n = 12), TTS was applied immediately after liver resection. The experiment lasted for 48 hours; the TTS was changed once after 24 hours from the beginning of application.

Results. In either group, there was no significant difference in the weight of liver remnant gain and in biochemical blood parameters at 48 hours after EHR. Assessment of the mitotic index (MI) of hepatocytes 48 hours after EHR revealed a significant increase in MI in both groups in comparison with the baseline (before liver resection) equal to 0.14 ± 0.07‰. The MI in group 1 and group 2 animals was 12.70 ± 4.9‰ and 17.43 ± 4.90‰, respectively (p ≤ 0.05).

Conclusion. Studies on the regenerative activity of sodium aminodihydrophthalazinedione TTS on an experimental EHR model in rats showed that this drug form had a pronounced stimulating effect on the mitotic activity of liver cells.

Current research shows that some of the pathogenetic processes behind structural destruction of bioprosthetic valves are largely similar to those involved in the development of atherosclerotic vascular lesions and native valve calcification. These processes include lipid and leukocyte infiltration, typical for both prosthetic and native tissues. They are accompanied by formation of foam cells, excessive production of matrix-degrading enzymes and increased oxidative stress. This fact suggests that some approaches to conservative treatment of atherosclerosis may be useful for prolonging the lifespan of bioprosthetic valves.

Organ transplantation is an effective treatment for many end-stage diseases. However, reperfusion injury constitutes a major complication of transplantation, which is associated with microcirculatory disorders and aggregation of blood corpuscles. Red blood cells (RBC) play an essential role in maintaining hemodynamic and rheological properties of the blood. Moreover, the study of mechanisms of changes in RBC functional indices is an urgent task. The main indicator of RBC functioning is the stability of RBC membrane structure. The issue of RBC membrane modification in organ transplantation has not been studied so far. Objective: to study the protein composition of RBC membranes, their aggregation and electrokinetic parameters in liver and kidney recipients, as well as in related kidney and liver fragment donors before and after operation. Research materials. Blood of 12 kidney recipients and 5 related kidney donors, 8 liver recipients and 4 related liver fragment donors – 1–2 hours before surgery, 1 week, 1, 2, 7, 10, 12 months after surgery. The control group consisted of 8 healthy volunteers. Research methods. Protein separation was done by Laemmli electrophoresis. RBC electrophoretic mobility, which characterizes the electrokinetic properties of cells, was measured by microelectrophoresis. Aggregation was calculated microscopically by counting unaggregated RBCs. Obtained values were compared by Mann-Whitney U test. Results. Examination of the RBC membrane of kidney recipients revealed a significant decrease in the amount of Band 3 protein and glycophorin before and after transplantation. Band 3 protein levels reduced at 1 month, glycophorin reduced at 7 months after surgery, with a maximum decrease in these protein fractions by more than 50% by 7 days compared with control values. There was also a decrease in spectrin content for 2 months after surgery with a maximum decrease of 30% by 1 month. In liver recipients, analysis of RBC membrane proteins revealed a decrease in the amount of glycophorin before surgery and further decrease at 2 months of post-transplant period. The maximum decrease in this index was 72% by 7 days after surgery. In addition, there was a fall in spectrin and Band 3 protein levels at 1 month by more than 60% relative to the control values. In donors, there were changes in the protein fraction of RBC membranes in the long-term post-operative period: spectrin and Band 3 protein levels reduced by 2 times at month 2 in kidney donors, while glycophorin levels reduced by 2.3 times at month 1 after operation in liver donors. Similarly, both groups of donors had increased actin levels at month 1 after surgery. The revealed changes in protein levels in the protein phase of RBC membranes were combined with functional indices of RBCs. In kidney recipients, decreased RBC electrophoretic mobility and increased aggregation were detected at 2 months. In liver recipients, the changes in these indicators were at 1 month. A decrease in RBC electrophoretic mobility was detected in donors of both groups. Conclusion. Changes in RBC membrane electronegativity are associated with changes in glycophorin and Band 3 protein levels, whereas in RBC aggregation process in liver/kidney recipients, the structural and functional disorders in the interrelationships of such membrane proteins as spectrin, Band 3 protein, and glycophorin, are significant factors. Alteration of actin determines inhibition of RBC aggregation growth in donors.

Background. Attitude towards organ donation is predominantly positive in the UK, however, donation rate remains low. To develop more effective interventions, this research aims to examine the behavioural barriers in organ donations using Q methodology to elicit patterns of overlap among different barriers and motivators.

Method. A Q methodology study was conducted with 40 participants aged 19–64 were asked to rank 47 statements on issues that are associated with organ donation. By-person factor analysis using Centroid method and Varimax rotation was conducted to bring out patterns in the way statements were ranked to obtain groupings of participants who had arranged the statements in similar fashion.

Results. Four viewpoints were extracted: The Realist, the Optimist Hesitant, the Pessimist Determinant and the Empathetic. Salient barriers to organ donation presented in each viewpoint suggest that perceived lack of knowledge, anxiety, mistrust in the healthcare system and lack of cue to action are the main barriers to organ donation. Consensus statements suggest that religion and family agreement are inconsequential if attitude to organ donation is well formed.

Conclusion. There are different attitudes around deceased organ donation that were uncovered using Q methodology. These results suggest that people respond to behavioural change campaigns differently depending in their own perceptions on organ donation. We argue that a paradigm shift in behavioural interventions is underpinned by understanding the overlapping yet distinctive nature perceived perspectives.

Objectives: despite the annual increase in living donors and the positive and negative implications following organ donation, this issue had become a significant challenge for donors. The present study aimed to analyze the experiences and views of living donors to organ donation implications.

Material and Methods. The present study was performed using qualitative content analysis. Twenty participants were selected using the purposive sampling method; data were collected by semi-structured interviews and analyzed based on Lundman and Graneheim contractual content analysis method after implementing MAX 12.

Results. Data analysis elicitated 721 codes, 20 subcategories, six main categories, and two themes, including positive and negative implications of organ donation from the viewpoint of living donors. The main categories of positive effects resulting from organ donation included the «donor’s peace of mind», «fundamental strength», and «recipient’s achievements». On the other hand, the main categories of negative implications resulting from organ donation included «donor’s physical suffering», «damaged interactions», and «abandonment».

Conclusion. Increasing the number of living donors makes us consider it essential to understand the efficiency of its two-way implications on many aspects of donor and recipient. Thus, managing the negative impacts of living organ donation and strengthening its positive side emphasizes the need to increase the awareness of organ donation associations, develop health policies at higher levels, and, most importantly, improve the satisfaction of live organ donors

Objective: to study the views of the youth in the Republic of Tatarstan on organ donation and transplantation, to analyze their awareness and ideas about donor transplants and potential their willingness to become organ donors.

Materials and methods. An anonymous sociological survey of 880 respondents aged 18 to 35 from the Republic of Tatarstan was conducted in the period from January 1 to July 1, 2021. An 11-question questionnaire was developed using online service Google Forms. Participation in the survey was voluntary.

Results. Female and male respondents accounted for 79.0% and 21.0%, respectively; 34.2% of the respondents have or are receiving medical education. Among the respondents, 71.5% have a clear understanding of the term «organ donation», 27.4% are not sure of their understanding, 1.1% do not have a clear understanding. 56.8% consider the issue of organ donation for transplantation in the Republic of Tatarstan as a pressing matter, 3.5% do not see it so, while 39.7% found it difficult to answer. After death, 35.9% would agree to become donors, 39.5% probably would agree, 9.3% probably would disagree, 5.6% strongly disagrees, 9.7% found it difficult to answer. The most common associations with organ donation were positive: 34.5% associate it with «life», 25.1% with «help», and 22.0% with «lifeline».

Conclusion. Young people in the Republic of Tatarstan are ready for a healthy debate of the problem of organ donation and most of them see it as a noble course. Given the interest in the problem and lack of awareness by the target audience, it is advisable to include independent academic disciplines on transplantology and organ donation in the curriculums of medical universities in the country. It is necessary to attract modern interdisciplinary information and educational resources to promote organ donation among the Russian public.

Objective: to evaluate the safety and efficacy of hypothermic oxygenated machine perfusion (HOPE) for kidney grafts obtained from expanded criteria donors (ECD).

Materials and methods. From June 2018 to June 2021, 200 surgeries involving kidney transplants from deceased donors were performed at Botkin City Clinical Hospital. Of these, 123 were men (61.5%) and 77 were women (38.5%). The mean age was 47.62 ± 11.69 (20–73) years. In 102 cases, kidney grafts were procured from ECD. In 92 recipients (90.2%) of kidney transplants from an expanded criteria donor, static cold storage done according to the standard technique was used to preserve the organ; these patients constituted observation group 1. In 10 recipients (9.8%), hypothermic oxygenated perfusion was used in addition to static cold preservation; these patients formed observation group 2.

Results. No 30-day mortality was recorded in both observation groups. The mean static cold storage time in group 1 patients was 612.33 ± 178.88 (133–1180) minutes. Overall incidence of delayed graft function was 26.5% (53/200). Incidence of delayed graft function was 19.3% (19/98) for organs from standard donors using static cold storage and 35.8% (33/92) for ECD organs. Twenty-five patients (12.5%) had postoperative complications. Postoperative complications with delayed graft function were diagnosed in 12 patients, which was 22.6% (12/53), with immediate function in 13 patients, which was 8.8% (13/147). Mean cold storage time in group 2 patients was 319.11 ± 110.24 (311–525) minutes. Mean HOPE time was 202.34 ± 21.48 (150–210) minutes. Delayed graft function was recorded in 1 group 2 patient (10%). No complications, including perfusion-related one, were recorded in this group.

Conclusion. The unique technique used at Botkin City Clinical Hospital for HOPE in kidney transplant is safe. It provides a low risk of delayed graft function for ECD kidneys.