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УДК 619:616.36:636.028
Liver transplantation programme in Syzganov's National Scientific Center of Surgery
S. Eguchi1, M. Takatsuki1, A. Soyama1, S. Cho1, D. Toksanbayev2, N. Sadykov2, M. Doskhanov2, A. Zharasbayev2
1 Nagasaki University Hospital, Nagasaki, Japan
2 JSC "Syzganov's National Scientific Center of Surgery", Almaty, The Republic of Kazakhstan
Аннотация. В Республике Казахстан, паценты с терминальными стадиями заболеваний печени представляют значительную проблему. Программа развития трансплантации печени началась в стране в декабре 2011 г, и к сентябрю 2014г в шести различных центрах республики проведено более 40 операций. Основной проблемой, препятствующей ширкому внедрению трансплантации печени в стране является слабоеразвитие посмертного органного донорства, в связи с особенностями ментальности населения. В связи с этим, медицинское сообщество было вынуждено начать программе развития трансплантации печени нетрадиционным способом - трансплантации печени от прижизненных доноров начали проводиться в остутствии опыта проведения трансплантации печени от посмертных доноров. В то же время, данный факт продемонстрировал, что общий уровень развития медицины в стране достаточно высок, для внедрения подобных сложных хирургических вмешательств.
Методы: В период с декабря 2011г, в АО «Национальный научный центр хирургии им. А.Н. Сызганова» было проведено 15 трансплантаций печени взрослым реципиентам с терминальными стадиями заболеваний печени. 12 операций проведены редуцированным граф-том, от прижизненных доноров; 3 операции - целой печенью, полученной от посмертных доноров.
Результаты: С начала развития программы развития трансплантации печени в АО «Национальный научный центр хирургии им. А.Н. Сызганова», отмечается улучшение как непосредственных интраопераци-онных показателей, так и общих результатов лечения целевой группы пациентов. На сегодня, наибольший период наблюдения после ТП составляет 32 месяца. Из 15 прооперированных реципиентов, 10 (66,7%) ведут нормальный образ жизни, получают минимальные дозы иммуносупрессивных препаратов. Среди реципиентов с циррозами печени вирусной этиологии, случаев реин-фекции вирусных гепатитов отмечено не было.
Заключения: Предварительные результаты показывают, что развитие программы трансплантации печени в Казахстане имеет хорошие перспективы. При этом, развитие трансплантации печени от посмертных доноров является предпочтительным, в связи с высоким риском развития осложнений у прижизненных доноров.
Ключевые слова: Терминальная стадия заболевания печени, трансплантация печени.
Abstract
Background: In the Republic of Kazakhstan, patients with end-stage chronic liver disease present a significant problem. Liver transplantation (LT) programme started in December 2011, and for September 2014, more than 40 liver transplant operations was performed in six different hospitals of the country. The main problem that hinders the wide implementing of liver transplantation in country is poor development of regularity of cadaveric organ donation system, due to specific mentality of the population and imperfect legislation. This fact has gained medical society for kind of un-traditional way of development of liver transplantation - living donor liver transplantation programme started before having any experience of cadaveric organ transplantation. At the same time, this experience was spectacular for demonstration of the general level of development of medicine in the country, for presenting such kind of advanced surgical operations.
Results: Since starting of LT programme in Syzganov's National Scientific Center of Surgery, results is improving both in a matter of surgical technique and in outcomes of treatment of target group of patietns. The greatest period of follow-up of patients after LT is 32 months for today. From 15 operated recipients, 10 (66.7%) leads a normal lifestyle, receiving a minimal immunosuppressive therapy. In patients with cirrhosis of viral etiology, there are no cases of viral hepatitis reinfection.
Introduction
Organ transplantation is devinitely an example of exciting technologies in modern medicine, which offenly appears as an only radical, justified by medical, social and economic points of view, method of treatment of end stage diseases. Comparing other organ transplantations, liver transplantation is a one of the most complicated operation [1]. Around 50 years ago, a dream of liver transplantation come true for clinical practice, and for today exists as a routine procedure for treatment of patients with end stage liver disease. For today, over 20000 liver transplantations are performing per year in the World, but number of patients in "Waiting list" increases progressively [2].
In the Republic of Kazakhstan, patients with chronic liver disease, including its end stages, presents a significant problem and respectively are under strong control of the Ministry of Healthcare and Welfare of the country. Before 2011, liver transplantation was not abailable in the country, despite of high level of hepatopancreatobiliary surgery and readiness of some leading centers through experimental workshops on phantoms and animals.
Liver transplantation programme started in December
Журнал Национального научного центра хирургии им. А.Н. Сызганова
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80%
□ Living donor liver transplntations
□ Deceased donor liver transplantations
Figure 1 - Ratio of living and deceased donors liver transplantations (December 2011 - July 2014)
□ B-LC □ BD-LC DC-LC □ BDC-LC □ NBNC-LC DPBC □ AIH DBA
Figure 2 - Ethiology of end-stage liver disease of transplanted patients
end stage liver disease was presented as below (fig. 2): 10 patients (66.6%) have had liver cirrhosis caused by viral hepatitis; other cases distributed between autoimmune hepatitis (13.3%), primary biliary cirrhosis (6.67%), secondary biliary cirrhosis founded on congenital biliary atresia (6.67%), idiopatic liver cirrhosis (6.67%). The patients' age ranged from 20 to 52 years. MELD score ranged from 13 to 25.
In case of living donor liver transplantation, acceptance of person from potential recipient's family as a living related donor of a fragment of liver was decided individually in every case. The final decision was basing both on the data of standard clinical diagnostic tests, which could demonstrate the fact that the potential donor is physicaly and mentaly healthy person, as well as on data of structural features of the liver of donor, with understanding the safe way of obtaining of high-quality graft, valuable in its functions and sufficient in its volume. Living donor procedure could not be planned without confidence the procedure has minimal risks for the donor.
Since December 2011, in Syzganov's National Scientific Center of Surgery provided 12 living donor liver transplantations for adult recipients with end-stage liver diseases. Appropriate candidate for liver's fragment donation was a relative elder than 18 and younger than 45 years, compatible with the recipient anthropometrically, without liver and other organs diseases, blood type identical/ compatible with the recipient.
By relation degree, most of the donors of liver fragments were siblings (brothers or
2011, and for September 2014, more than 40 liver transplant operations was performed in six different hospitals of the country. Most of operations were successful, despite of the numerous medical and organization problems.
For today, the main problem that hinders the wide implementing of liver transplantation in Kazkhstan is poor development of regularity of cadaveric organ donation system, due to specific mentality of the population and imperfect legislation. This fact has gained medical society for kind of un-traditional way of development of liver transplantation - living donor liver transplantation programme started before having any experience of cadaveric organ transplantation. At the same time, this experience was spectacular for demonstration of the general level of development of medicine in the country, for presenting such kind of advanced surgical operations.
Aim of work
To implement liver transplantation in clinical practice.
Material and methods
Since December 2011, in Syzganov's National Scientific Center of Surgery was performed 15 liver transplantations for adult recipients with end stage liver disease. 12 cases done with split grafts from living donors, another 3 - with full liver grafts from cadaveric donors (fig. 1).Ethiology of
sisters) - 6 cases (50.0%). In two cases donors was parents of the patients (16.6%); in another two - patient's nephews (16.6%); in one case (8.3%) - patient's son and in another one (8.3%) - patient's wife.
The selection of graft type have been basing of precise calculations of the alleged graft and volume remaining fragment of the liver from a donor, in each case. For effective operation outcome, an estimated liver fragment's volume harvesting from a donor defined for at least 35% of the recipient's liver volume, according to generally accepted recommendations for preventing a small-for-size syndrome [3, 4]. At the same time, the remnant liver fragment for donor also defined not less than 35% of total donor liver, to prevent the possibility of liver failure for the donor. Data resulting from the computed tomographic angiography, treated in «Synapse Vincent ®» software (Fugi Telecom, Japan), was a basis for 3D volumetry of fragments of donor's liver (fig. 3).
Three operations from deseased donors done after multiorgan harvesting (heart, liver and kidneys).
The management of patients in postoperative period based on clinical protocols from different countries: Russia, Belarus, Japan and Turkey, with adaptation corresponding capabilities of the health system of the Republic of Kazakhstan.
Postoperatively, all patients were in the intensive care unit, for general intensive therapy, adoption of immunosuppressive therapy, antiviral therapy etc. The duration of stay of the
Figure 3 - CT-angiography and 3D volumetry of liver's fragments
patient in the intensive care unit averaged 16 days. After stabilization, the recipients were transferred to the general ward. Hospital stay ranged from 35 days to 75 days. Sanitary and epidemiological conditions in intensive care and overall units observed strictly.
Patients with liver cirrhosis in the outcome of viral hepatitis B (8 cases, 66.67%), received postoperative antiviral therapy for prevention of acute postoperative hepatitis «B» (Lamivudine, Tenofovir and Entokavir). Twice we used HBIG, for the control of anti-Hbs.
From three (25.0%) of transplanted recipients with viral hepatitis C liver cirrhosis, one currently receives antiviral therapy; the other two are planned for liver biopsy to determine the extent of fibrosis; then, it will be determined the indications for antiviral therapy.
Protocol of immunosuppressive therapy in each case determined individually, according to a balance between immunosuppression and immunocompetence.
Results
1) Donors in LDLT surgery. Extended left lobe for grafting was preferred in 6 cases (60%); right lobe (30%) - in 3 cases and 1 case - the right posterior lateral sector of the liver (10%). Duration of donor's surgery was between 5 hours 10 minutes and 8 hours and 15 min. The most significant intraoperative blood loss was 1350 ml, in the initial stages of implementation of technology; with the improvement of surgical techniques, the use of modern blood-preserving equipments and surgical wound retractors, blood loss significantly reduced, for 70 ml in the best case.
Complications observed in three donors in early postoperative period. Two donors (16.6%) have had a biliary complications. Postoperative bile leakage on the control drainage observed in one case (8.3%) and stopped spontaneously in five weeks after surgery. Obstruction of the left hepatic duct after harvesting of the right lobe in another one case (8.3%). There was a trial of biliary stenting, which failed because of technical problems, and patient underwent for Roux-en-Y hepaticojejunostomy.
In one case (8.3%), donor had postoperative vomiting, because of adhesions between small curvature of the stomach and cut surface of the liver, after extended left lobe herwesting. The trials of treatment therapy for improving the motility of the gastrointestinal tract was not succeed, and
finally donor underwent re-laporatomy for adhesiolis, 11 month after harvesting.
2) Recipients in LDLT surgery. Five patients from twelve died in early stage after LT (POD 1-10), in different reasons but generally because of hepatic failure, and another one patient - 7 month after LT because of lungs infection. Retrospective analyse shows, that all survived recipients have had more stable (large) liver graft, like a right lobe, and patients who was not survived had smaller graft - extended left lobe or right posterior sector of liver, even GW/SLV ratio was acceptable (more than 35%). All survived recipients had no any significant complications.
3) Recipients in DDLT surgery. There were no any deaths of recipients after DDLT operations, but one case was complicated with infecting of Pseudomonas Aeruginosa.
For today, the greatest period of follow-up of patients after LT is 32 months. Of the 15 operated recipients, 10 (66.7%) lead a normal lifestyle, receiving a minimal immunosuppressive therapy (tacrolimus, with a target concentration of 3-5 ng / ml). In patients with cirrhosis of viral etiology, there are no cases of viral hepatitis reinfection.
Conclusions: 1. Preliminary findings based on a small experience showed a good perceptiveness of developing of Liver Transplantation programme in Kazakhstan. There is reason to believe that the number of such operations in the Republic of Kazakhstan will increase in the future.
2. The development of living fonor liver transplantation programme in the Republic of Kazakhstan looks a good option; however, cadaveric donor transplantation programme is preferable for developing, because of high risk of complications in donor' surgery.
Literature
1. C.J.E. Watson, J.H. Dark. Organ transplantation: historical perspective and current practice //Br. J. Anaesth. (2012) 108 (suppl 1): P.29-42.
2. Silvia Vilarinho, Richard P. Lifton. Liver Transplantation: From Inception to Clinical Practice // Cell. Volume 150, Issue 6, 14 September 2012, Pages 1096-1099.
3. Dahm F, GerogievP., Clavien P.A. Small-for-size syndrome after partial liver transplantation: definition, mechanisms of disease and clinical Implications //Am I Transplant 2005; 5: 2605-2610.
4. Kiuchi Y, Tanaka K, Ito T, Oike F, Ogura Y, Fujimoto Y, Ogawa K. Small-for-size graft in living donor liver transplantation: how far should we go? //Liver Transplantation 2003; 9: S29-S35.
