Organ Preservation Techniques Research Articles

Paediatric donor lung preservation using Paragonix BAROguard.

Paediatric lung transplantation is a lifesaving option in selected patients with end-stage lung disease. Favourable long-term outcomes are limited by impaired mucus clearance, increased risk of infection resulting from immunosuppression, and chronic lung allograft dysfunction. Organ preservation techniques play an important role in the quality of donated organs. Barotrauma to donated lungs may arise from a combination of excessive recruitment manoeuvres and altitude change during air transportation. The Paragonix BAROguard Donor Lung Preservation System is an FDA-approved advanced organ recovery system that maintains continuous airway pressure of 15 cm of water during transportation of the donated lung(s) to the recipient. The Paragonix LUNGguard monitors temperature during transportation of donor lung(s), while the new BAROguard monitors both temperature and pressure during transportation of donor lung(s). In this publication, we present technical aspects of advanced preservation of paediatric donor lungs using the Paragonix BAROguard Donor Lung Preservation System.

Risk and Reward: Nationwide Analysis of Cardiac Transplant Center Variation in Organ Travel Distance and the Effects on Outcomes.

The 2018 UNOS allocation policy change deprioritized geographic boundaries to organ distribution, and the effects of this change have been widespread. The aim of this investigation was to analyze changes in donor transplant center distance for organ travel and corresponding outcomes before and after the allocation policy change. The UNOS database was utilized to identify all adult patients waitlisted for heart transplants from 2016 to 2021. Transplant centers were grouped by average donor heart travel distance based on whether they received more or less than 50% of organs from >250 miles away. Descriptive statistics were provided for waitlisted and transplanted patients. Regression analyses modeled waitlist mortality, incidence of transplant, overall survival, and graft survival. Centers with a longer average travel distance had a higher mean annual transplant volume with a reduction in total days on a waitlist (86.6 vs. 149.2 days), an increased cold ischemic time (3.6 vs. 3.2 h), with no significant difference in post-transplant overall survival or graft survival. The benefits of reducing waitlist time while preserving post-transplant outcomes extend broadly. The trends observed in this investigation will be useful as we revise organ transplant policy in the era of new organ procurement and preservation techniques.

Revolutionizing deceased donor transplantation: How new approaches to machine perfusion broadens the horizon for organ donation

Solid organ transplantation is lifesaving for persons with end-stage organ disease. Thanks to advancements in organ preservation, surgeons are now able to successfully transplant organs that were previously considered high risk for poor graft function. Innovations in perfusion machine types, preservation solutions and additives to preservation solutions have significantly improved the ability to utilize organs previously thought unusable.Newer organ preservation techniques are offering a promising outlook for extending graft longevity and improving transplant outcomes. This review explores the impact of deceased donor type on graft quality and highlights emerging strategies designed to improve the function and viability of deceased donor organs.

A 25-year scoping review of the organ donation system in Malaysia: past, present, and future.

Organ donation and transplantation are integral components of modern medicine. This scoping review thoroughly explores the historical evolution, current status, and future prospects of organ donation and transplantation in Malaysia. Historically, Malaysia faced significant challenges in establishing a robust organ transplantation system, with various factors hindering organ donation efforts. Currently, Malaysia continues to struggle with stagnant donation rates despite collaborative efforts from various sectors. There is an urgent need to amend the 50-year-old Human Tissue Act to strengthen the legal framework for organ donation and address ethical concerns. Looking to the future, Malaysia could adopt a soft opt-out system and prioritize advancements in organ preservation techniques by exploring new sources of organs through the donation after circulatory death program. Continued efforts are necessary to enhance education programs for professionals and the public, dispelling myths about organ donation and effectively educating on the concepts of brain death. Malaysia strives to create a more accessible future for organ transplantation, aligning with the Sustainable Development Goals to reduce the burden of organ failure and improve the population's health and well-being.

Combined Organ Transplantation in Patients with Advanced Liver Disease.

Transplantation of the liver in combination with other organs is an increasingly performed procedure. Over the years, continuous improvement in survival could be realized through careful patient selection and refined organ preservation techniques, in spite of the challenges posed by aging recipients and donors, as well as the increased use of steatotic liver grafts. Herein, we revisit the epidemiology, allocation policies in different transplant zones, indications, and outcomes with regard to simultaneous organ transplants involving the liver, that is combined heart-liver, liver-lung, liver-kidney, and multivisceral transplantation. We address challenges surrounding combined organ transplantation such as equity, utility, and logistics of dual organ implantation, but also advantages that come along with combined transplantation, thereby focusing on molecular mechanisms underlying immunoprotection provided by the liver to the other allografts. In addition, the current standing and knowledge of machine perfusion in combined organ transplantation, mostly based on center experience, will be reviewed. Notwithstanding all the technical advances, shortage of organs, and the lack of universal eligibility criteria for certain multi-organ combinations are hurdles that need to be tackled in the future.

Assessing the degree of hepatic ischemia-reperfusion injury using physiologically based pharmacokinetic modeling of sodium fluorescein disposition in ex vivo machine-perfused livers.

Ischemia-reperfusion injury (IRI) is an intrinsic risk associated with liver transplantation. Ex vivo hepatic machine perfusion (MP) is an emerging organ preservation technique that can mitigate IRI, especially in livers subjected to prolonged warm ischemia time (WIT). However, a method to quantify the biological response to WIT during MP has not been established. Previous studies used physiologically based pharmacokinetic (PBPK) modeling to demonstrate that a decrease in hepatic transport and biliary excretion of the tracer molecule sodium fluorescein (SF) could correlate with increasing WIT in situ. Furthermore, these studies proposed intracellular sequestration of the hepatocyte canalicular membrane transporter multidrug resistance-associated protein 2 (MRP2) leading to decreased MRP2 activity (maximal transport velocity; Vmax) as the potential mechanism for decreased biliary SF excretion. We adapted an extant PBPK model to account for ex vivo hepatic MP and fit a six-parameter version of this model to control time-course measurements of SF in MP perfusate and bile. We then identified parameters whose values were likely insensitive to changes in WIT and fixed them to generate a reduced model with only three unknown parameters. Finally, we fit the reduced model to each individual biological replicate SF time course with differing WIT, found the mean estimated value for each parameter, and compared them using a one-way ANOVA. We demonstrated that there was a significant decrease in the estimated value of Vmax for MRP2 at the 30-min WIT. These studies provide the foundation for future studies investigating real-time assessment of liver viability during ex vivo MP.NEW & NOTEWORTHY We developed a computational model of sodium fluorescein (SF) biliary excretion in ex vivo machine perfusion and used this model to assess changes in model parameters associated with the activity of MRP2, a hepatocyte membrane transporter, in response to increasing warm ischemia time. We found a significant decrease in the parameter value describing MRP2 activity, consistent with a role of decreased MRP2 function in ischemia-reperfusion injury leading to decreased secretion of SF into bile.

Perfusion Techniques in Kidney Allograft Preservation to Reduce Ischemic Reperfusion Injury: A Systematic Review and Meta-Analysis.

The limited supply and rising demand for kidney transplantation has led to the use of allografts more susceptible to ischemic reperfusion injury (IRI) and oxidative stress to expand the donor pool. Organ preservation and procurement techniques, such as machine perfusion (MP) and normothermic regional perfusion (NRP), have been developed to preserve allograft function, though their long-term outcomes have been more challenging to investigate. We performed a systematic review and meta-analysis to examine the benefits of MP and NRP compared to traditional preservation techniques. PubMed (MEDLINE), Embase, Cochrane, and Scopus databases were queried, and of 13,794 articles identified, 54 manuscripts were included (n = 41 MP; n = 13 NRP). MP decreased the rates of 12-month graft failure (OR 0.67; 95%CI 0.55, 0.80) and other perioperative outcomes such as delayed graft function (OR 0.65; 95%CI 0.54, 0.79), primary nonfunction (OR 0.63; 95%CI 0.44, 0.90), and hospital length of stay (15.5 days vs. 18.4 days) compared to static cold storage. NRP reduced the rates of acute rejection (OR 0.48; 95%CI 0.35, 0.67) compared to in situ perfusion. Overall, MP and NRP are effective techniques to mitigate IRI and play an important role in safely expanding the donor pool to satisfy the increasing demands of kidney transplantation.

Open organ preservation for laryngeal cancer

As the treatment for laryngeal cancer has evolved over several decades, organ preservation has remained one of the goals of treatment. While chemoradiation therapy is the most widely used treatment modality, open surgical preservation techniques for laryngeal cancer continue to be an option in the surgeon's armamentarium. A summary of the history, anatomic considerations, principles of organ preservation and specific partial laryngectomy techniques are discussed in this review.

Optimal strategies for prevention of ischemia‑reperfusion injury in heart transplantation with prolonged cold ischemia time (review)

The shortage of organs for transplant remains a major challenge in transplantology. Transporting donor organs over long distances increases cold ischemia time, which is a risk factor for ischemia-reperfusion injury (IRI). In the face of critical shortages, the method and timing of organ preservation are crucial in increasing the donor pool. This paper examines the approaches, benefits, and drawbacks of organ preservation techniques used around the world.

Intra-arterial chemotherapy for locally advanced nasal cavity and sinonasal tract cancers

Introduction. Malignant tumors of the nasal cavity and sinonasal tract are rare, less than 3 % of all of the head and neck malignant neoplasm. The leading treatment is combined methods with surgery as a first step. However, operation is limited in a locally advanced process due to requires the use of complex reconstructive techniques and removal of aesthetic and functionally important structures. In this regard, the interest of specialists is understandable in use of organ-preserving techniques with comparable oncological results. Intra-arterial chemotherapy has shown high effectiveness in various localizations of malignant neoplasms, so its use in locally advanced tumors of the nasal cavity and sinonasal tract seems promising.Aim. To evaluate the results of complex treatment of patients with locally advanced cancer of the nasal cavity and sinonasal tract using induction intra-arterial chemotherapy.Materials and methods. The study included 28 from 2017 to 2023 with locally advanced cancer of the nasal cavity and sinonasal tract underwent TPF induction intra-arterial chemotherapy, followed by radiation or chemoradiotherapy. The primary endpoint of the study was survival, secondary – objective response rate, treatment toxicity and the possibility of organ preservation.Results. The median follow-up was 19.1 months. We obtained results for all patients of 1-year overall survival – 85.7 % (T3 – 100 %, T4a – 92.7 %, T4b – 55.6 %), and 1-year progression-free survival – 66.7 % (T3 – 75 %, T4a – 71.4 %, T4b – 50 %), respectively. The response rate after intra-arterial chemotherapy was 85.2 %. Overall survival and progression-free survival did not differ significantly between patients with complete response, partial response, and stable disease. However, in patients with a complete response after chemoradiotherapy, 1-year overall survival was 100 % (p = 0.009) and progression-free survival – 90 % (p <0.001). The main side effect in patients in the study was the development of neutropenia (35.7 %), and occurrence of neurological complications was noted in 10.7 %. Of the 35.7 % of patients with tumor orbital invasion, survival with preserved visual function in the first year of life was 80 %; all patients retained vision; as a result of treatment, not a single patient underwent surgery with exenteration.Conclusion. Induction intra-arterial chemotherapy in treatment of patients with locally advanced cancer of the nasal cavity and sinonasal tract demonstrates high efficiency and a high level of complete responses with a fairly low level of toxicity, and also allows preserve the eye function for the majority of patients.

Ex vivo lung perfusion and the Organ Care System: a review.

With the increasing prevalence of heart failure and end-stage lung disease, there is a sustained interest in expanding the donor pool to alleviate the thoracic organ shortage crisis. Efforts to extend the standard donor criteria and to include donation after circulatory death have been made to increase the availability of suitable organs. Studies have demonstrated that outcomes with extended-criteria donors are comparable to those with standard-criteria donors. Another promising approach to augment the donor pool is the improvement of organ preservation techniques. Both ex vivo lung perfusion (EVLP) for the lungs and the Organ Care System (OCS, TransMedics) for the heart have shown encouraging results in preserving organs and extending ischemia time through the application of normothermic regional perfusion. EVLP has been effective in improving marginal or borderline lungs by preserving and reconditioning them. The use of OCS is associated with excellent short-term outcomes for cardiac allografts and has improved utilization rates of hearts from extended-criteria donors. While both EVLP and OCS have successfully transitioned from research to clinical practice, the costs associated with commercially available systems and consumables must be considered. The ex vivo perfusion platform, which includes both EVLP and OCS, holds the potential for diverse and innovative therapies, thereby transforming the landscape of thoracic organ transplantation.

Modification of Preservative Fluids with Antioxidants in Terms of Their Efficacy in Liver Protection before Transplantation.

Transplantation is currently the only effective treatment for patients with end-stage liver failure. In recent years, many advanced studies have been conducted to improve the efficiency of organ preservation techniques. Modifying the composition of the preservation fluids currently used may improve graft function and increase the likelihood of transplantation success. The modified fluid is expected to extend the period of safe liver storage in the peri-transplantation period and to increase the pool of organs for transplantation with livers from marginal donors. This paper provides a literature review of the effects of antioxidants on the efficacy of liver preservation fluids. Medline (PubMed), Scopus, and Cochrane Library databases were searched using a combination of MeSH terms: "liver preservation", "transplantation", "preservation solution", "antioxidant", "cold storage", "mechanical perfusion", "oxidative stress", "ischemia-reperfusion injury". Studies published up to December 2023 were included in the analysis, with a focus on publications from the last 30 years. A total of 45 studies met the inclusion criteria. The chemical compounds analyzed showed mostly bioprotective effects on hepatocytes, including but not limited to multifactorial antioxidant and free radical protective effects. It should be noted that most of the information cited is from reports of studies conducted in animal models, most of them in rodents.

Clinical experience of combined organ-preserving treatment of laryngopharyngeal cancer with spread to the cervical esophagus

Introduction. Laryngopharyngeal cancer accounts for about half of the total number of malignant neoplasms of ENT organs. Despite the availability of examination, in most patients tumors of this localization are detected at late stages, and the long-term results of treatment of locally advanced cancer of the larynx remain unsatisfactory.Clinical case. This article presents two clinical cases of combined organ-preserving treatment of laryngopharyngeal cancer with spread to the cervical esophagus. At the first stage, patients underwent organ-preserving surgical treatment with a reconstructive plastic component according to the methodology developed at the A.F. Tsyb Medical Radiological Research Center – branch of the National Medical Research Center of Radiology. Then a postoperative course of chemoradiotherapy was carried out.Conclusion. The use of combined organ-preserving techniques using displaced skin-muscle flaps in the treatment of locally advanced laryngopharyngeal cancer involving the cervical esophagus allows in some cases to avoid crippling surgery, preserve the larynx and achieve satisfactory functional results, which significantly improves the quality of life of patients.

Normothermic ex vivo perfusion of deceased donor kidneys and its clinical potential in kidney transplantation outcomes.

In recent years, normothermic machine perfusion (NMP) has emerged in conversation surrounding organ preservation and transplantation techniques with the goal of improving patient and clinical outcomes. This is in great attempt to address the rate of non-utilization and the shortage of available organs in kidney transplantation. This focus in mind, normothermic perfusion presents itself as a potential tool to mimic physiological conditions and improve current preservation methods, such as static cold storage. This review serves to improve understanding of the observed connection between the consequences of ischemia and reperfusion injury and traditional preservation techniques as well as how renal NMP may mitigate these issues. Previous studies suggest that reducing time in static cold storage methods by promoting the normothermic perfusion model results in decreased delayed graft function and post-transplant complications. This review also aims to present the immense clinical potential NMP has on future kidney transplantation success and what this means for the fields of nephrology and transplantation. While great strides have been made to evaluate normothermic perfusion's impact on kidney graft viability and transplant success, future research into unified protocol, clinically relevant biomarkers, cost-utility analysis, and use with associated therapeutic and imaging modalities is paramount.

Possibilities of differential diagnosis of uterine leiomyosarcoma

Uterine leiomyosarcoma is a rare malignant neoplasm consisting of smooth muscle cells, characterized by an aggressive course and poor prognosis.
 Differential diagnosis of uterine leiomyosarcoma is challenging due to the nonspecificity and low severity of symptoms, particularly in the early stages. Patients with uterine leiomyosarcoma commonly present with complaints in of pelvic pain, abnormal uterine bleeding, and symptoms of compression of nearby organs. The same clinical symptoms are characteristics of patients with uterine leiomyomas.
 Leiomyosarcoma is often detected after histologic examination of material obtained during surgery for uterine myoma. At the same time, preoperative verification of the malignant nature of the neoplasm is crucial in determining the optimal tactics of surgical treatment. For instance, the use of organ-preserving techniques and morcellation in the treatment of presumed uterine leiomyoma may result in the dissemination of tumor cells and significantly worsen the prognosis in patients with undiagnosed leiomyosarcoma.
 This review discusses existing methods of preoperative diagnosis of uterine leiomyosarcoma, their efficacy, as well as the possibilities of application in clinical practice.

Acute complication posttransplant: primary allograft dysfunction.

Heart transplant is the gold standard treatment for patients with end-stage heart failure, improving both quality of life and survival. Despite advances in donor and recipient management, primary graft dysfunction (PGD) remains the most common cause of morbidity and mortality in the early posttransplant period. This review summarizes recent discoveries in the underlying pathophysiology, risk prediction and management of PGD. The incidence of PGD appears to be rising and it is not clear whether this is due to better recognition or secular changes in transplant practice. The utilization of donation after circulatory death organs for transplant is a further consideration for the development of PGD. Organ transport systems and preservation techniques may help to prevent PGD. As some of the risk factors for developing PGD remain modifiable, we summarize the current evidence for prevention and management of PGD. A better understanding will allow us to appropriately manage donors and recipients to reduce the complex interactions that lead to PGD. The development of an international consortium provides the opportunity for deep phenotyping and development of contemporary risk prediction models for PGD, which may reduce the incidence and consequent early mortality associated with heart transplantation.

Organ-Preserving Surgeries on the Spleen: Evolution of Concepts

One of the current trends in modern surgery is the study of the spleen injuries and diseases, in particular, its traumatic ruptures which are a fairly common pathology, being the most prevalent among all injuries of the abdominal organs. The improvement of hemostasis options and the choice of tactics in the surgical treatment of the spleen pathologies are crucial. Few recent decades have been dominated by the idea that splenectomy is the major surgical option for the spleen damage and diseases. Currently, as reported in Russia and globally, surgical tactics implying the use of organ-preserving surgeries in case of the spleen injury are being widely developed and applied.If compared with organ-preserving operations, there are negative changes in the cellular and humoral links of the immunity after splenectomy. A significant number of proposed spleen preserving options are grouped into: conservative treatment, wound tamponades, splenic sutures, segmental resection, ligation of splenic arteries, wound bonding, infrared contact coagulation, autotransplantation of splenic tissue. Currently, surgeons have quite a lot of experimental and clinically tested techniques in their arsenal that allow successfully performing organ-preserving spleen surgery. However, none of them lacks of drawbacks. These drawbacks are quite diverse, ranging from the inability to provide guaranteed reliable hemostasis to technological and economic aspects of the operation, thus, the search for novel organ-preserving techniques remains promising.

Hepatic allograft rejection after liver transplantation: Clinicopathological debates!

Liver transplantation (LT) represents a life-saving surgical procedure and is considered the current standard of care for the majority of patients having end-stage liver disease. As known, significant progress in organ preservation techniques, perioperative care, and strict immunosuppression protocols are associated with favorable patient/graft survival post-LT. Hence, proper evaluation of liver allograft-related complications among survivors has paid great attention, particularly the rejection sequel after LT. It is a seriously underestimated cause of allograft injury, which pushes researchers for understanding the exact pathogenesis of different types and proper time diagnosis for better management of such complications. However, it still represents a challenge because of the complexities related to diagnosis and histopathology. Hence, increasing clinical awareness with earlier diagnosis of post-LT rejection is essential through stimulating further studies. Therefore, our review will focus on the clinicopathological debates regarding liver allograft loss after transplantation.

Skin cancer in solid organ transplant recipients: still an open problem.

In the last two decades, the optimization of organ preservation and surgical techniques, and the personalized immunosuppression have reduced the rate of acute rejections and early post-transplant complications. However, long-term graft survival rates have not improved over time, and evidence suggest a role of chronic calcineurin inhibitor toxicity in this failure. Solid organ transplant recipients may develop chronic dysfunction/damage and several comorbidities, including post-transplant malignancies. Skin cancers, mostly non-melanoma skin cancers (squamous cell carcinoma and basal cell carcinoma), are the most common malignancies in Caucasian solid organ transplant recipients. Several factors, together with immunosuppression, may contribute to the susceptibility for skin cancers which, although often treatable, could be associated with a much higher mortality rate than in the general population. The rapid identification and treatment (including reduction of immunosuppression and early surgical treatments) have an important role to avoid an aggressive behavior of these malignancies. Organ transplant recipients with a history of skin cancer should be followed closely for developing new and metastatic lesions. Additionally, patient education on the daily use of sun-protective measures and the recognition of the early signs (self-diagnosis) of coetaneous malignancies are useful preventive measures. Finally, clinicians should make themselves aware of the problem and build, in every clinical follow-up center, collaborative network involving transplant clinicians, dermatologists and surgeons who should work together to easily identify and rapidly treat these complications. In this review, we discuss the current literature regarding the epidemiology, risk factors, diagnosis, preventive strategies and treatments of skin cancer in organ transplantation.

Immune cell dynamics deconvoluted by single-cell RNA sequencing in normothermic machine perfusion of the liver

Normothermic machine perfusion (NMP) has emerged as an innovative organ preservation technique. Developing an understanding for the donor organ immune cell composition and its dynamic changes during NMP is essential. We aimed for a comprehensive characterization of immune cell (sub)populations, cell trafficking and cytokine release during liver NMP. Single-cell transcriptome profiling of human donor livers prior to, during NMP and after transplantation shows an abundance of CXC chemokine receptor 1+/2+ (CXCR1+/CXCR2+) neutrophils, which significantly decreased during NMP. This is paralleled by a large efflux of passenger leukocytes with neutrophil predominance in the perfusate. During NMP, neutrophils shift from a pro-inflammatory state towards an aged/chronically activated/exhausted phenotype, while anti-inflammatory/tolerogenic monocytes/macrophages are increased. We herein describe the dynamics of the immune cell repertoire, phenotypic immune cell shifts and a dominance of neutrophils during liver NMP, which potentially contribute to the inflammatory response. Our findings may serve as resource to initiate future immune-interventional studies.