CC BY
25
II. ХИРУРГИЯ
LIVER TRANSPLANTATION IN SYZGANOV NATIONAL SCIENTIFIC CENTER OF SURGERY
УДК 616.36-089
Toksanbayev D.S., Sadykov N.K., Zharasbayev A.M., Kusainov A.Sh., Doskhanov M.O., Moldabekov Ye.T., Duisenbekov M.K., Kaniyev Sh.A.
Department of hepatopancreatobiliary surgery and liver transplantation, National Scientific Center of Surgery named after A.N. Syzganov, Almaty
ABOUT THE AUTHORS
Toksanbayev Daniyar Saparovich - head of the department of liver transplantation, can. med., a high level certificate physician, surgeon
Abstract
In the Republic of Kazakhstan patients with end-stage chronic liver disease present a significant problem and respectively are under strong control of the Ministry of Healthcare and Welfare of the country. Liver transplantation (LT) program started in December 2011, and by September 2015, more than 50 liver transplant operations were performed in six different hospitals of the country.
In Syzganov National Scientific Center of Surgery 19 liver transplantations for adult recipients with different ethiology end-stage liver diseases were performed. In 15 (79%) cases, liver graft has been taken from living related donors (LDLT), in other 4 (21%) cases - from deceased donors (DDLT). Post-operative management was followed according to internal clinical protocol of Syzganov National Scientific Center of Surgery, which was established basing of clinical protocols from different countries: Russia, Belarus, Japan, South Korea and Turkey, with adaptation corresponding capabilities of the health system of the Republic of Kazakhstan.
Preliminary findings demonstrate a good perceptiveness of developing of Liver Transplantation program in Kazakhstan.
A.H. Cызfaнoв этындз^! ¥лттьщ эдмыми xиpypгия opтaлыfыньщ бэуьф тpaнcплaнтaцияcыньщ тэжipибeci
Toкcaнбaeв Д.С., Caдыкoв H.K., Жapacбaeв A.M., K¥caинoв A.0., Дocxaнoв M.O., Moлдaбeкoв E.T., ДYЙceбeкoв M.K., Kaниeв 0.A.
A.H. Сь^нов aтындafы Улттык, шлыми xиpypгиялык1 opтaлыfы, Гeпaтoпaнкpeaтoбилapлы xиpypгияcы мен бayыp тpaнcплaнтaцияcы, Aлмaты
Ацдатпа
Квкейкестг: Бayыp aypybrnbiH, тepминaлды кeзeœдepiнe шaлдыккßн пaциeнттep Kaзaкcтaн Pecпyбли-кacындa aйтapлыктaй пpoблeмa бoлып тaбылaды. Пaциeнттepдiœ ocbi кaтeгopияcыныœ paдикaлды тypдe eмдeyдiœ жшыз rypi бayыpды ayыcтыpып крн,дьipy бoлып тaбылaды. Кдзipn тaœдa бayыpды тpaнcплaн-тaттay oтacын œacaya Kßзaкcтaннын, vyp.лi вфлepiндeгi 1000 пaциeнт мyкraж. Бayыpды тpaнcплaнтaттay бafдapлaмacы (LT) 2011 жылдын, жeлтoк,caн aйынaн бacтaлды, aiprí тaœдa Kaзaкcтaндa бayыpды ayûcm-pып ^нды^у rypFыcынaн eлдeгi rypлi бec клиникaдa (Acтaнa к., Aлмaты к.) 50 acтaм oпepaция жacaлды.
Kвптeгeн мeдицинaлык пeн yйымдacтыpyшылык пpoблeмaлapfa кapaмacтaн, oпepaциялapдыœ бacым-дьюы cdni шыкты.
Emen бayыpды тpaнcплaнтarrayды irne acыpyдa ^eprírn тигiзeтiн нeгiзгi пpoблeмacы - rypfындapдыœ нaкты длт жэнe зaцнaмaнын, жeтiлмeгeндiгiнe бaйлaныcты, мэйтдoнopлыfы нaшap дaмыfaн бoлып тaны-лущ. Б±л дepeк fipi дoнopдaн бayыpды тpaнcплaнтaттayдыœ жылдaм дaмyынa ceбeп бoлды.
Harnœeëepi: Бayыpды тpaнcплaнтaттay бafдapлaмacыныœ бacтaлy cэтiнeн бacтaп A.H.CызFaнoв aтындafы Улттык гылыми xиpypгия opтaлыfындa eмдey нэтижeлepi жэнe xиpypгиялык тexникacы кYннeн кунт кapaй жaкcapyдa. Бayыpды тpaнcплaнтaттayдaн ^йш пaциeнттepдi кßдafaлayдыœ eœ ул^н мepзiмi 32 aйды к±paйды. Бayыpды тpaнcплaнтaттay oтacынaн ^йн 19 пaциeнтriœ iшiнeн 12 пaциeнт, ятни (63.2%) минимaлды иммyнocyпpeccивтiк emi aлyымeн, кдлыпты вм'ф cypm œamp. Bиpycты этиoлoгияcыныœ бay-ûp циppoзынa шaлдыккaн aypyлapындa oтa жacafaннaн ^йн ж'т виpycты гeпaтит дepтi aныкт'aлмafaн.
Key words
donor, kidney, reception, transplantation, organ.
TYérn ceздep
бayыp aypybrnbiœ тepминaлды ^eni, бayыpды тpaнcплaнтaт-тay (aybicrbipbrn ^нды^у).
ОБ АВТОРАХ
ТоксанбаевДанияр Сапарович - заведующий отделением трансплантации печени ННЦХ им. А.Н. Сызганова, к.м.н., врач высшей категории, хирург, e-mail: dr_tox@mail.ru
Ключевые слова
терминальная стадия заболевания печени, трансплантация печени
Трансплантация печени в ННЦХ им. А.Н. Сызганова
Токсанбаев Д.С., Садыков Н.К., Жарасбаев А.М., Кусаинов А.Ш., Досханов М.О., Молдабеков Е.Т., Дуйсебеков М.К., Каниев Ш.А.
Национальный научный центр хирургии им. Сызганова,
Отделение гепатопанкреатобиларной хирургии и трансплантации печени, Алматы
Аннотация
Актуальность: Пациенты с терминальными стадиями заболевания печени представляют собой значительную проблему в Республике Казахстан. Единственное радикальное лечение у этих категорий пациентов является трансплантации печени. В настоящее время трансплантация печени нуждается более 1000 пациентов из различных регионов Казахстана. Программа трансплантации печени (1Т) началась с декабря 2011 года, в настоящий момент в Казахстане выполнена, более 50 операций по трансплантации печени была выполнена в пяти различных клиниках страны.
В настоящее время стране выполнена более 50 операций по пересадке печени была выполнена в 5 различных клиниках страны (г.Алматы и г.Астана). Большинство операций были успешными, несмотря на многочисленных медицинских и организационных проблем.
Основная проблема, которая, мешает реализации трансплантации печени в стране - является слабое развитие трупного донорства, в связи с конкретной ментальности населения и несовершенство законодательства. Этот факт явился причиной быстрого развития трансплантации печени от живого донора.
Результаты: С момента начала программы трансплантации печени в Национальном научном центре хирургии имени А.Н. Сызганова, результаты лечения и хирургической техники улучшается день за днем. Наибольший срок наблюдения пациентов после трансплантации печени 32 месяцев. Из 19 пациентов 12 (63.2%) ведет нормальный образ жизни после трансплантации печени, получая минимальную иммуносупрессивную терапию. У пациентов с циррозом печени вирусной этиологии, не отмечался острый вирусный гепатит в послеоперационном периоде.
Relevance. Organ transplantation is an example of the exciting technologies in modern medicine, opens the radical treatment of patients who were considered hopeless. Comparing with other organ transplants, liver transplantation is one of the most complex operations. The first successful liver transplant performed even more 50 years ago, today transplantation as a radical treatment is being successfully implemented to patients with terminal liver deseases in more than 150 countries around the world. Despite the huge number of liver transplantation in a year, the number of patients in a "waiting list" does not decrease.
In the Republic of Kazakhstan patients with chronic liver disease, including its last stages, present a considerable challenge, and, accordingly, are under strict control of the Ministry of health and social welfare of the country. Despite the good security and a high level of hepatopancreatobiliary surgery, the willingness of some surgical centers, liver transplantation was not practiced in the country.
Liver transplantation in the country has always been important, and the radical treatment of patients with terminal liver diseases has been actively discussed. Then, specialists in different fields were trained in various foreign clinics. In NSCS named
after A.N. Syzganov the "waiting list" of patients in need of a liver transplantation has been created. The algorithm of examination and treatment of patients with terminal liver diseases were carried out. Experimental works have been conducted on animals, acquired equipment and improved material and technical equipment of the clinic.
The program of liver transplantation in the Republic of Kazakhstan began in December 2011, when for the first time in the context of NSCS named after A.N. Syzganov" together with the transplantologists of the Republic of Belarus the liver transplantation has been conducted from the lifetime donor with a good result.
This was an awesome introduction, non-standard way of development of programs with no experience of TP from post-mortem donor, we started from lifetime donors. At the same time, this experience was an impressive demonstration of the overall level of medicine in the country, for the submission of such advanced surgical operations. This fact was a "trigger mechanism" for the medical community of the country.
Later, between the NSCS named after A.N. Syz-ganov and Nagasaki biomedical university hospital a memorandum on cooperation was signed, the
■ Transplantation of a "part" of liver from live donor
■ Transplantation of a "whole" liver of from postmortal donor
Figure 1
Relationship between live and postmortal liver donor (December 2011-January 2014)
goal of which was to help professionals in the organization of the TP and its further development in the Republic of Kazakhstan. The next series of operations were conducted jointly with the transplanto-logists of Japan, under the direction of Professor Susumu Eguchi.
From the beginning of 2014 in the NSCS named after A.N. Syzganov the liver transplantation is performed independently by surgeons without inviting foreign specialists.
To date, the main problem that impedes the liver transplantation in the country - is a weak development of corpse donation, in connection with the specific mentality of the population and the imperfection of the legislation. This fact led to the rapid development of live donor liver transplantation.
The aim of the work - implementation of the program of liver transplantation from live and postmortal donors in clinical practice.
Materials and methods. From December 2011 to November 2014 at hepatopancreatobiliary surgery and liver transplantation department of the NSCS named after A.N. Syzganov there were carried out 19 liver transplantations to adult recipients with terminal stages of liver diseases of different etiology. Among them in 15 (79%) cases the liver transplantation has been performed from the live donor and in 4 (21%) cases from postmortal donors
(fig. 1).
Recipient age ranged from 16 to 55 years old; 5 men (26.4%), 14 women (73.6%). MELD scale (model for end-stage liver disease) at the time of operation ranged from 13 to 25 years old, according to the severity of the condition of patients with grade «B» and «C» on the Child-Turcotte-Pugh.
On the etiology of the terminal stage liver disease, patients were as follows: Cirrhosis of the liver in chronic viral hepatitis «B»- 8 (with delta-agent - 6), cirrhosis of the liver in chronic viral hepatitis «C» - 4, cirrhosis of the liver in the outcome of viral hepatitis «C» combined with hepatocellular carcinoma - 1 (two nodes up to 3.0 cm in diameter),
cryptogenic cirrhosis - 1, cirrhosis of the liver in the outcome of autoimmune hepatitis - 3, primary biliary cirrhosis - 1, secondary biliary cirrhosis in biliary duct congenital pathology - 1 (5.6%).
In the case of liver transplantation from the live donor, as a donor liver selection decision was made individually in each case. The final decision was based on the data of standard clinical diagnostic tests that would demonstrate the fact that the potential donor is a physical and mental healthy human, as well as according to the structural characteristics of the donor's liver, the choice of a safe way to obtain high-quality transplant in function and in its entirety. We always held the elections of early intervention from the donor with minimal risk to the life of the donor.
Live donors were from 18 to 50 years old. The majority of living donors were siblings - in 9 cases, in 2 cases - parents, and in 2 cases -nephews, one case was with son of the patient and in another case - the spouse of the recipient. When selecting living donors the following criteria have values: (a) an anthropometric donor-recipient relationship, b) compatibility of blood group c) without accompanying pathology, d) age not older than 55 years.
Liver volume measurement was held by means of a special program on the computer tomography. Computed tomography with contrast bolus (om-nipak, vizipak, and so on, the amount of contrast at least 150.0 ml) plays an important role not only to define the vascular structures of the liver, but also in liver volume measurement. Measurement of total liver and liver to be abstracted is conducted in venous phase. Total liver volume equates to 1.8-2.0 % of total body weight or measured by the formula of Urata K. (total liver = (ml) = 706.2 x total body area (m2) + 2.4. Volume of liver phragment to be abstracted is measured on anatomical lines that divide the segments, sectors and shares. Amount of intake of liver snippet must be more than 35-40% for the recipient or GRWR (ratio of graft weight-to-weight of recipient) must make over 0.8%, the
Figure 2
Etiology of end-stage liver disease
■ cirrhosis of the liver in the outcome of viral hepatitis11C"
■ cirrhosis of the liver in the outcome of viral hepatitis "C" combined with hepatocellular carcinoma
□ cryptogenic cirrhosis
□ cirrhosis of the liver in the outcome of autoimmune hepatitis
■ primary biliary cirrhosis
□ secondary biliary cirrtiosis
remaining part of the liver for the donor must total at least 33-35%, if less than 30% remains with the donor then the donor should abandon due to a large risk of liver failure in the postoperative period.
There is special institution as «Republican coordination center of transplantation» that governs the organization of postmortal donation. The Center has regional coordinators in each region of Kazakhstan, which, in the case of a potential organ donor, give information to the center. Thanks to the work of the coordnational center in a country since 2013 organ transplantations from postmortal donors were began to conduct.
In our Center four recipients (22.2%) were performed liver transplantation from postmortal donors. Donors in all cases were patients with determined brain death, aged from 32 to 57 years. Causes of brain death were intracranial hemorrhage (n=3), severe oxidstress treatment and craniocerebral trauma (n=1). The quality of donor liver, rated to the common criteria, was satisfactory in all cases.
In two cases, the donor liver was obtained in the course of the multiorgan recuperation (heart, liver and kidney) within the city of Almaty. In two cases, recuperation and transporting of donor organs from other regions of the country were organized. In one
case, the donor organ was 2200 km from transplant centre (Aktobe city), transportation of the donor organ was organized by air ambulance with support of the Ministry of health of the Republic of Kazakhstan, in this case cold ischemia of liver transplant lasted 11 hours, and in another case a donor organ was located 520 km from the transplantation center (Taraz city), transportation authorities organized a special equipped vehicles, in this case cold ischemia lasted 12 hours and 30 minutes.
For treatment and postoperative management of patients we have used experience and clinical protocols from different countries (Japan, Turkey, Belarus, Russia). Based on these protocols, in JSC «NSCS named after A.N. Syzganov» its own protocol for diagnosis and treatment of patients with TSZP after the TP, satisfying possibilities of system of health of the Republic of Kazakhstan, was developed and approved.
In the postoperative period, all patients were in intensive care units, where the overall intense, immunosupressus therapy, prevention of infectious and viral complications were carried out. Length of the patient standing in the intensive care unit was 10-16 days on average; after stabilization, recipients were placed in a common chamber. Hospital
Figure 4
Selection of liver fragment of the live donor for graft formaion n=13.
stay ranged from 35 to 75 days. Sanitary and epi-demiological conditions in intensive care in general ward were strictly adhered.
Patients with liver cirrhosis in the outcome of viral hepatitis «B» (8 cases) in aftercare period received antiviral therapy to prevent relapse of acute hepatitis «b» (lamivudine, tenofovir and entoca-vir). In 2 cases hepatitis «b» immunoglobulin was used, under the control of anti-Hbs, for prevention of acute viral hepatitis in the postoperative period, against a background of immunosuppression.
Among 5 transplanted recipients with viral hepatitis «C», one is currently receiving antiviral therapy; the other three are scheduled for a liver biopsy, to determine the degree of fibrosis; afterwards, the indications for antiviral therapy will be determined.
Protocol of immunosupressive therapy in each case is determined individually, with the balance between immunocompetence and immunosuppres-sion.
Results and discussion
Recuperation of liver fragments from live donors for transplantation. Extended left lobe was preferred in 6 cases (40 %) the right lobe (53.3 %) in 8 cases and in 1 case - the right rear lateral sector of right lobe of the liver (6.7 %).
The duration of the operation of the donor was between 5 hours 10 minutes and 8 hours 15 minutes. The most significant intraoperative blood loss was amounted to 1350 ml.
Complications have been observed in the three donors in the early postoperative period. The two donors (13.3%) have had biliary complications. In one case there have been bile leakage by drainage up to 50.0 ml a day, in the dynamics of volume reduced to 0. The drain was removed. In one case the narrowing of the left lobe duck in the confluence area after right-sided hemihepatectomy was mentioned. To correct narrowing of left lobe duck in the confluence area a stenting of the left lobe duct was performed, but without effect. Therefore, cholangiojejunostomy on Roux loop of jejunum.
In one case (6.6%) the donor was vomiting after the left-side hemihepatectomy, due to adhe-
sions between the curvature of the stomach and the exsect liver edge. Endoscopic correction of duodenal obstruction was performed, but no effect. With a view to improving the duodenal obstruction relaparatomy, adhesiotomy were performed. In postoperative period the duodenal obstruction was cupped off. Discharged with a satisfactory condition.
Recipients after transplantation of liver fragments. Postoperative complications were observed in 9 cases (60%). 6 patients have had surgical complications: bleeding (4 cases, in all cases there was relaparatomy, stop bleeding), reperfusion injury (1 case), thrombosis of the hepatic artery (1 case; relaparatomy was performed, reanastomosis between hepatic artery of transplant and digestive gland of the recipient artery). 3 patients have had immunological problems (crises of exclusion); humoral rejection of them in 1 case (a pulse therapy with Basiliximab was performed, positive effect), cellular rejection in 2 cases (resolved against pulse therapy). Also one patient has had infectious complications (pneumonia). Postoperative lethality was 31.6% (6 recipients). Causes of death were on one occasion: ACCD; thrombosis of the hepatic artery; multiple organ dysfunction in hemorrhagic shock; humoral rejection episode; sepsis with pneumonia.
Recipients after liver transplant from postmortal donor. Postoperative lethality was not mentioned. One patient (5.2%) has had an infectious complication - double sided lower-lober pneumonia, with a bacteriological examination of blood and sputum a Pseudomonas aeruginosa 106 was revealed. A minimal immunosuppressive therapy and antibacterial therapy for sensitivity was conducted. Against the backdrop of antibacterial therapy a bakteremia was cupped off.
To date, the biggest period of observation of the recipient after liver transplantation is 38 months. For 19 operated recipients, 12 (63.1%) patients keep a normal life, with a minimum of immunosup-pressive therapy (tacrolimus with concentration of 3-5 ng/ml). Patients with liver cirrhosis of viral origin, do not have acute viral hepatitis in the postoperative period.
Analysis of the recipient after liver transplantation
Liver volume Whole liver Right lobe Left lobe Right lateral sector
Recipients 4 8 6 1
Percentage for the recipient 80%-120% 50-70% 30-40% 30%
GRWR 1,6-2,4% 1-1,4% 0,6-0,8% 0,6%
Complications 1 0 5 1
Lethality 0 1 5 1
Retrospective analysis showed that all of the recipients were survived of more stable (large) liver transplant (GRWR more than 0.8%) especially when right lobes of the liver implantation was performed. Postoperative lethality was noted in recipients whom the implantation of small liver lobes was performed to (GRWR less than 0.8%). Also there was noted that the use of the left lobe of the liver, strictly according to indications, is due to the low level of graft.
Conclusion
Preliminary conclusions based on little experience have shown good prospects of develop-
ing of the programme of liver transplantation in Kazakhstan. The number of such operations in the Republic of Kazakhstan will increase in the future.
Development of live donor liver transplantation in the Republic of Kazakhstan is a good option; however, the programme development of postmortal donor liver transplantation is considered to be better option, because of the high risk of complications in live donor and increase the numbers of patients on the "waiting list".
Use of liver transplant more than 35-40% for the recipient provides minimal post-operative complications and postoperative lethality.
References
1. Urata K., Kawasaki S., Matsunami H., Hashikura Y., Ikegami T., Ishizone S., Momose Y., Komiyama A., Makuuchi M. Calculation of child and adult standard liver volume for liver transplantation.
2. Sarah L White, Richard Hirth, Beatriz Mahillo, Beatriz Dominguez-Gil, Francis L Delmonico, Luc Noel, Jeremy Chapman, Rafael Matesanz, Mar Carmona, Marina Alvarez, Jose R Niiez, Alan Leichtman. The global diffusion of organ transplantation: trends, drivers and policy implications. Bull World Health Organ. Nov 1, 2014; 92(11): 826-835.
3. Jacqueline G. O'Leary, Rita Lepe, Gary L. Davis. Indications for Liver Transplantation Gastroenterology, Volume 134, Issue 6, Pages 1764-1776.
4. Brown R.S. Jr, Kumar K.S., Russo M.W., Kinkhab-wala M, Rudow D.L., Harren P., Lobritto S., Emond J.C. Model for end-stage liver disease and Child-Turcotte-Pugh score as predictors of pretransplanta-tion disease severity, posttransplantation outcome, and resource utilization in United Network for Organ Sharing status 2A patients. Liver Transpl. 2002 Mar; 8(3): 278-84.
5. Mazzaferro V., Regalia E., Doci R., Andreola S., Pul-virenti A., Bozzetti F., Montalto F., Ammatuna M., Morabito A., Gennari L. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996; 334 (11): 693.
