Transplantation: indications, preparation, technique

Clinical transplantology is a complex of medical knowledge and skills that enable the use of transplantation as a method of treating various diseases that do not respond to traditional methods of treatment.

The main areas of work in the field of clinical transplantology:

• identification and selection of potential recipients of donor organs;
• performing appropriate surgical intervention;
• conducting adequate immunosuppressive treatment to maximize the life of the transplant and recipient.

Clinical transplantology develops on the basis of the most modern methods of diagnostics, surgery, anesthesiology and resuscitation, immunology, pharmacology, etc. In turn, the practical needs of clinical transplantology stimulate the development of these areas of medical science.

The development of clinical transplantology was facilitated by the experimental work of the Russian scientist V.P. Demikhova in the 40-60's of the last century. He laid the foundations of surgical techniques for transplantation of various organs, but the clinical development of his ideas took place abroad.

The first successfully transplanted organ was the kidney (Murray J., Boston, USA, 1954). It was a related transplantation: the donor was an identical twin of a recipient suffering from chronic renal failure. In 1963, T. Shartzl in Denver (USA) initiated clinical liver transplantation, but real success was achieved only in 1967. In the same year, H. Bariard in Cape Town (South Africa) performed the first successful heart transplantation. The first transplantation of a pancreatic pancreas to a human was performed in 1966 by V. Kelly and R. Lillichay at the University Clinic of Minnesota (USA). A patient with diabetes mellitus with chronic renal failure was implanted with a pancreas segment and a kidney. As a result, for the first time, almost complete rehabilitation of the patient was achieved - failure of insulin and dialysis. The pancreas is the second organ after the kidney, successfully transplanted from a living related donor. A similar operation was also performed at the University of Minnesota in 1979. The first successful lung transplant was performed by J. Hardy in 1963 at the Mississippi State Hospital (USA), and in 1981 B. Reitz (Stanford, USA) succeeded by transplanting the heart complex -lungs.

1980 in the history of transplantology is considered the beginning of the "cyclosporin" era, when after the experiments of R. Calne in Cambridge, Great Britain, a fundamentally new immunosuppressant, cyclosporine, was introduced into clinical practice. The use of this drug significantly improved the results of organ transplantation and allowed achieving long-term survival of recipients with functioning transplants.

The end of the 1980s and the beginning of the 1990s was marked by the emergence and development of a new direction in clinical transplantology - the transplantation of liver fragments from living donors (Raya S, Brazil, 1988; Strong RW, Australia 1989; Brolsh H., USA, 1989 ).

In our country the first successful kidney transplantation was performed by Academician B.V. Petrovsky April 15, 1965 This transplantation from a living related donor (from mother to son) initiated the development of clinical transplantology in domestic medicine. In1987, Academician V.I. Shumakov successfully transplanted the heart for the first time, and in 1990 a group of specialists from the Russian Research Center for Surgery of the Russian Academy of Medical Sciences (RSCC RAMS), under the supervision of Professor A.K. Yeramishantseva performed the first orthotopic liver transplantation in Russia. In 2004, the first successful transplantation of the pancreas (using its distal fragment from a living related donor) was performed, and in 2006 - the small intestine. Since1997, the Russian Academy of Medical Sciences has performed a related liver transplant (SV Gauthier).

Purpose of transplantation

Medical practice and numerous studies of domestic authors indicate the presence of a large number of patients suffering from terminal liver, kidney, heart, lung, intestinal lesions, in which the commonly used methods of treatment only temporarily stabilize the patients' condition. In addition to the humanitarian importance of transplantation as a radical type of care that allows to save life and restore health, its socio-economic effectiveness is also obvious in comparison with the long, expensive and unpromising conservative and palliative surgical treatment. As a result of the use of transplantation, the society is returned to its full members with preserved working capacity, the possibility of creating a family and the birth of children.

Indications for transplantation

World experience of transplantation indicates that the results of the intervention largely depend on the correctness of the evaluation of indications, contraindications and the choice of the optimal moment of the operation in a particular potential recipient. The course of the disease requires analysis from the perspective of life expectancy both in the absence and after transplantation, taking into account the need for lifelong drug-induced immunosuppression. Ineffectiveness of therapeutic or surgical methods of treatment is the main criterion in the selection of potential recipients of donor organs.

When determining the optimal moment of transplantation in children, the age of the child is of great importance. The observed improvement in the results of organ transplantation with their age and body weight increase is not a reason for delay, for example, with liver transplantation with biliary atresia or acute hepatic insufficiency. On the other hand, the relatively stable state of the child, for example, with cholestatic liver lesions (biliary hypoplasia, Caroli's disease, Byler's disease, etc.), chronic renal failure with effective peritoneal or hemodialysis allows to postpone the operation until it reaches a more stable state against conservative treatment . However, the time limit for postponing transplantation should not be unreasonably prolonged, so that the delay in the child's physical and intellectual development does not become irreversible.

Thus, the following principles and criteria for selecting potential recipients for organ transplantation are postulated:

• Presence of indications for transplantation:
  • irreversibly progressing organ damage, manifested by one or more life-threatening syndromes;
  • inefficiency of conservative therapy and surgical methods of treatment.
• Absence of absolute contraindications.
• A favorable life forecast after transplantation (depending on the nosological form of the disease).

Indications for transplantation are very specific for each specific organ and are determined by the spectrum of nosological forms. At the same time, contraindications are quite universal and should be taken into account when selecting and preparing recipients for transplantation of any organ.

Preparation for transplantation

Preoperative preparation is carried out with a view to possible improvement of the state of health of a potential recipient and elimination of factors that may adversely affect the course of the operation and the postoperative period. Thus, we can speak about two components of preoperative treatment of potential recipients of donor organs:

• treatment aimed at eliminating or minimizing relative contraindications to transplantation;
• treatment aimed at maintaining the patient's life in anticipation of transplantation and optimizing his physical condition at the time of the operation.

The waiting list is a document for the registration of patients who need a transplant of one or another organ. It records the passport data, the diagnosis, the date of its establishment, the severity of the disease, the presence of complications, as well as the data necessary for the selection of the donor organ - blood group, anthropometric parameters, HLA-typing results, the level of pre-existing antibodies, etc. Data are constantly updated in view of entering into the list of new patients, changing their status, etc.

The patient is not included in the waiting list of the donor organ in the presence of any foci of infection outside the organ to be replaced, since they can cause serious complications against the background of immunosuppressive therapy in the posttransplant period. In accordance with the nature of the infectious process, its treatment is carried out, the effectiveness is controlled by serial bacteriological and virological studies.

Drug immunosuppression, traditionally carried out to minimize autoimmune manifestations of chronic liver, kidney, heart, lungs and involving large doses of corticosteroids, creates favorable conditions for the development of various infectious processes and the existence of a pathogenic flora that can activate after transplantation. As a result, corticosteroid therapy is canceled in the process of preoperative preparation, after which all the foci of bacterial, viral and / or fungal infection are sanitized.

In the process of examination of patients, especially children, violations of nutritional status of varying severity are detected, correction of which with high-calorie mixtures containing large amounts of protein is difficult in patients with liver and kidney diseases. For this reason, it is advisable to use nutrients, consisting predominantly of amino acids with branched chains, keto analogs of essential amino acids and vegetable protein, replenishing the deficiency of fat-soluble vitamins and minerals. Patients with intestinal insufficiency syndrome awaiting the transplantation of the small intestine must complete a full parenteral nutrition.

An important component of preoperative management of a potential recipient is psychological preparation.

Integral assessment of the patient's status indicators allows to determine the prognosis of the disease and assign the patient to one or another group in terms of the urgency of the transplantation:

• Patients in need of constant intensive care, require urgent surgery.
• Patients who require in-patient medical support usually need to perform the operation within a few weeks.
• Patients in a stable state can expect transplantation for several months, and they are periodically hospitalized to prevent the progression of complications of a chronic disease.

Donor organs for transplantation

Related transplantation has become possible due to the presence of paired organs (kidneys, lungs) and special anatomophysiological properties of some unpaired solid organs of a person (liver, pancreas, small intestine), and also through the steady improvement of surgical and parasurgical technologies.

At the same time, relationships within the triangle "patient-living donor-doctor" are built not only on the generally accepted deontological positions, when the prerogative is completely given to the patient, but with informed and voluntary decision-making by the donor.

[1], [2], [3], [4], [5], [6], [7], [8]

Features of surgical intervention in transplantation

The ideological basis of the operation in a living donor is the coupling of minimizing the donor risk and obtaining a high-quality transplant. These interventions have a number of distinctive features that do not allow them to be classified as general surgical manipulations:

• the operation is performed in a healthy person;
• complications entail a threat to the life and health of two people at once - the donor and the recipient;
• mobilization of an organ or separation of its fragment is performed in the conditions of the continuous circulation of this organ.

The main tasks of surgical technique and anesthesia in living donors:

• minimization of operating injury;
• minimization of blood loss;
• Exclusion of ischemic organ damage during surgical manipulations;
• Reduction of the time of thermal ischemia when taking a transplant.

[9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19]

Perfusion and preservation of a fragmentary graft

Regardless of the type of graft obtained immediately after its removal from the donor's organism, the graft is placed in a tray with sterile ice, where, after cannulation of the afferent vessel, perfusion is started with a preservative solution at a temperature of +40 ° C. Currently, in the practice of related transplantation, a preservative solution of "Custodiol" is more often used. The criterion of sufficiency perfusion is the supply of a pure (without admixture of blood) preservative solution from the mouth of the transplant vein. Next, the graft is placed in a preservative solution at a temperature of +40 ° C, where it is stored before implantation.

Operational characteristics

The implementation of transplantation can be hampered by the consequences of previous operations on the organs of the abdominal or thoracic cavity, so the decision to include such patients in the number of potential recipients is taken depending on the individual experience of the transplant surgeon.

Contraindications for transplantation

Contraindications to transplantation are understood to mean that the patient has any diseases or conditions that pose an immediate threat to life and not only can not be eliminated by transplantation, but can be aggravated by the performance of her or subsequent immunosuppressive therapy, leading to death. There is a certain group of conditions in which the performance of transplantation, even in the presence of indications, seems to be obviously meaningless or harmful from the perspective of a life expectancy for a particular patient.

Among the contraindications for organ transplantation are absolute and relative. As absolute contraindications consider:

• uncorrectable violations of the function of vital organs, including the central nervous system;
• infectious process outside the body to be replaced, for example, tuberculosis, AIDS, or any other non-treatable systemic or local infections;
• oncological diseases outside the body to be replaced;
• the presence of malformations accompanying the underlying disease, not subject to correction and not compatible with long life.

In the process of accumulating the experience of clinical transplantation, methods of training recipients and maintaining vital functions during their waiting for surgery were improved. Accordingly, some of the contraindications, previously considered absolute, passed into the category of relative contraindications, that is, conditions that increase the risk of intervention or complicate its technical implementation, but if successful, do not worsen the favorable prognosis after surgery.

Improvement of surgical and anesthesia techniques allowed to optimize the conditions of transplantation even in the newborn period. For example, the early age of the child was excluded from the number of contraindications. Gradually push the boundaries of the maximum age of the potential recipient, since contraindications are determined not so much by them as by concomitant diseases and the possibility of preventing complications.

In the process of preparing a patient for transplantation of a particular organ, a successful correction of the status is possible with minimization and even elimination of a number of relative contraindications (infections, diabetes, etc.).

[20], [21], [22], [23], [24], [25], [26], [27]

Reaction rejection and immunosuppressive treatment

Getting into the recipient organism, the transplant becomes the cause and the object of the immunological response. Reaction to the donor organ includes a whole complex of sequential cellular and molecular processes, which together lead to a clinical picture of the rejection syndrome. The main components of its occurrence are preexisting donor-specific HLA antibodies and "recognition" of the genetically alien HLA antigens by the immune system. By the mechanism of action on the tissues of the donor organ, exclusion is distinguished with a predominance of antibody activity (humoral, hyperactive rejection) and acute cellular rejection. It should be borne in mind that both mechanisms can be involved in the development of this reaction. In the late period after transplantation, the development of chronic rejection of the donor organ, which is based primarily on immunocomplex mechanisms, is possible.

The choice of protocol for immunosuppressive treatment depends on many factors: the type of donor organ, the coincidence of the blood group, the degree of tissue compatibility, the quality of the transplant and the initial state of the recipient. Immunosuppression at various stages of the post-transplant period changes in accordance with the manifestations of the reaction of rejection and the general status of the patient.

The use of related transplants greatly simplifies the conduct of drug-induced immunosuppression. This is especially noticeable when the immediate relatives of the recipient are the donors: parents or siblings. In such cases, a coincidence of three or four HLA antigens from the six standard diagnoses is observed. Despite the fact that the rejection reaction is certainly present, its manifestations are so insignificant that they can be stopped by smaller doses of immunosuppressants. The probability of a crisis of rejection of a related graft is very small and can be provoked only by unauthorized cancellation of drugs.

It is common knowledge that organ transplantation presupposes immunosuppressive treatment during the entire period of the functioning of the donor organ in the recipient organism. In comparison with other transplant organs, such as the kidney, pancreas, lung, heart and small intestine, the liver occupies a special position. It is an immunocompetent organ that has a tolerance to the immune response of the recipient. More than 30 years of transplantation experience showed that with proper immunosuppression, the average survival time of the hepatic transplant is much higher than that of other transplant organs. About 70% of recipients of the donor liver show a ten-year survival. Long-term interaction of the liver transplant with the recipient organism creates the so-called microchimerism, which provides favorable conditions for the gradual reduction of immunosuppressant doses up to corticosteroid withdrawal, and then, in a number of patients, until the drug immunosuppression is completely abolished, which is more real for recipients of related transplants in connection with the obviously greater initial tissue compatibility.

Methods and subsequent care

Principles of obtaining grafts from donors in a state of brain death

Donor organs are removed from the body of the deceased during a complex surgical intervention, involving the obtaining of the maximum possible number of cadaver organs suitable for transplantation to patients awaiting transplantation (multi-organ removal). In the multi-organ withdrawal, the heart, lungs, liver, pancreas, intestines, kidneys are obtained. The distribution of donor organs is performed by the regional donor organ coordination center in accordance with the general waiting list of all transplant centers operating in the region on the basis of indices of individual compatibility (blood group, tissue typing, anthropometric parameters) and information on the imperative of indications for transplantation in the patient. The procedure for multi-organ removal of organs is worked out by world transplant practice. There are various modifications to it, which make it possible to preserve the quality of organs as much as possible. Cold perfusion of organs with a preservative solution is made directly in the body of the deceased, after which the organs are removed and placed in containers, where they are transported to their destination.

The final preparation of the donor organs for implantation is carried out directly in the operating room, where the recipient is located. The purpose of the training is to adapt the anatomical features of the transplant to those of the recipient. Simultaneously with the preparation of the donor organ, the recipient is operated in accordance with the chosen implantation option. Modern clinical transplantology in the transplantation of the heart, liver, lungs, heart-lung and small intestine complex involves the removal of the affected organ followed by implantation of a donor organ (orthotopic transplantation) in its place. At the same time, the kidney and pancreas are implanted heterotopically, without necessarily removing the recipient's own organs.

Obtaining organs or their fragments from living (related) donors

The organs that can be obtained from a living donor without damaging its health are the kidney, liver fragments, the distal fragment of the pancreas, the small intestine site, and the lobe fraction.

The indisputable advantage of transplantation from a living donor is independence from the system of providing cadaver organs, and, accordingly, the possibility of scheduling the operation depending on the condition of the recipient.

The main advantage of a graft from a living donor is the quality of the organ, predicted by the selection and in some cases by the preparation of related donors. This is due to the fact that with a related donor, negative hemodynamic and drug effects on the perioperative stage of the donor are virtually excluded. For example, when using cadaveric liver, the probability of a more severe initial parenchyma lesion is always greater than with related transplantation. The modern level of hepatic surgery and methods of organ conservation allows obtaining a high-quality transplant from a living donor with minimal ischemic and mechanical damage.

Unlike organ transplantation, obtained posthumously, the use of an organ or a fragment of an organ from the nearest relative allows one to count on its more favorable immunological adaptation in the recipient organism due to similar HLA characteristics of haplotypes. Ultimately, the results of the leading transplant centers of the world indicate a better long-term survival of recipients and transplants after a related transplantation than after transplantation of cadaver organs. In particular, the period of "half-life" of the cadaveric kidney transplant is about 10 years, whereas for the related ones - more than 25 years.

Post-transplantation period

Under the posttransplant period is understood the life of the recipient with a functioning transplanted organ. The normal course of it in the adult recipient implies recovery from the initial disease, physical and social rehabilitation. In children, the post-transplant period should guarantee additional conditions, such as physical growth, intellectual development and puberty. The severity of the initial state of potential recipients of donor organs, the traumatism and duration of surgical intervention, combined with the need for post-transplantation immunosuppressive treatment, determine the specifics of conducting this contingent of patients. This implies active prophylaxis, diagnosis and elimination of complications, substitution therapy aimed at compensating previously disrupted functions, as well as monitoring the rehabilitation process.

Peculiarities of conducting a postoperative period in recipients

The presence of multiple risk factors, such as prolonged extensive surgical intervention, the presence of drains, drug-induced immunosuppression, long-term use of central venous catheters, is the basis for massive and prolonged antibiotic prophylaxis. To this end, the intraoperatively intravenous administration of cephalosporin group III or IV generation drugs at a dose of 2000-4000 mg / day (in children - 100 mg / kg x day) continues]. The change of antibacterial drugs is carried out depending on the clinical and laboratory picture and in accordance with the sensitivity of the microflora detected during bacteriological examination. All patients from the first day after transplantation are prescribed fluconazole in a dose of 100-200 mg / day for the prevention of fungal infection and ganciclovir in a dose of 5 mgDkgsut) for the prevention of cytomegalovirus, herpetic and Epstein-Barr infections. The period of application of fluconazole corresponds to the period of antibiotic therapy. The preventive course of ganciclovir is 2-3 weeks.

Correction of nutritional status with the most adequate replenishment of energy costs and timely compensation of protein metabolism disorders is achieved by balanced parenteral and enteral nutrition. In the first 3-4 days, all parenteral nutrition is administered to all recipients [35 kcal / (kilogram)), which is included in the protocol of infusion therapy. Substitution therapy is carried out by infusion of freshly frozen plasma in combination with a solution of albumin.

The need for a constant intake of corticosteroids, as well as the propensity to develop erosive and ulcerative lesions of the upper gastrointestinal tract, against the background of the stressful situation of the early postoperative period, obliges the appointment of H2-histamine receptor blockers, antacid and enveloping agents.

Organ transplantation allows to save life and restore health to a large number of patients with severe diseases that can not be cured by other methods. Clinical transplantology requires extensive knowledge from a transplant physician, not only in surgery, but also in the field of parasurgical specialties, such as intensive care and extracorporeal detoxification, immunology and medication immunosuppression, prevention and treatment of infections.

The further development of clinical transplantology in Russia implies the formation, organization and smooth functioning of the system of providing the organs with the concept of brain death. A successful solution to this problem depends, first of all, on the level of awareness of the population in the real possibilities of organ transplantation and the high humanism of organ donation.