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ТРАНСПЛАНТОЛОГИЯ
T. WROBLEWSKI
LIVER TRANSPLANT PROGRAM IN THE DEPARTMENT OF GENERAL, TRANSPLANT AND LIVER SURGERY, MEDICAL UNIVERSITY OF WARSAW
Medical University of Warsaw, Poland
Трансплантация печени является одним из самых сложных оперативных вмешательств, которые требуют не только высокого мастерства хирургов, но и тщательно организованной системы подготовки пациентов, надежной координации действий различных служб, наличия высокотехнологичного оборудования и системы послеоперационного наблюдения. В настоящей статье освещены вопросы истории становления службы трансплантации печени в Польше, современные потребности и возможности этой службы.
Описанные в статье подходы к определению показаний и выбору тактики оперативных вмешательств основываются на опыте выполнения 805 трансплантаций печени за более чем двадцатилетний период. Такой большой опыт позволил не только определить частоту возникающих осложнений, но и представить результаты по выживаемости пациентов с различной патологией.
Ключевые слова: ортотопическая трансплантация печени, программа по трасплантации печени, показания, осложнения, цирроз печени, первично склерозирующий холангит, печеночно-клеточный рак
Liver transplantation is one of the most complicated surgical interventions demanding not only high skills of surgeons but also a thoroughly organized system of patients' preparing as well as a reliable coordination of actions of various services, high-tech equipment and the system of postoperative observation. In the given article the questions the foundation history of the service of liver transplantation in Poland are illustrated as well as modern demands and possibilities of this service.
The described approaches to the determining indications and tactics choice of surgical interventions are based on 805 liver transplantations for more than a 20-year period. Such a wide experience permits not only to determine the complications frequency but also to present the results of patients' survival with various pathologies.
Keywords: orthotopic liver transplantation, liver transplantation program, indications, complications, liver cirrhosis, primarily sclerosing cholangitis, liver-cellular cancer
In 1967, three years after the first unsuccessful transplantation occurred, Thomas Starzl achieved the first success in performing orthotopic liver transplantation (OLTx). However, the intervention operation remained experimental and it took 16 more years to recognize it as a fully legal therapeutic procedure. Advances in immunosuppressive therapies such as the introduction of cyclosporine and its wide-spread use in patients after liver and kidney transplantation since 1983 have considerably improved transplantation success rates.
There are 125 liver transplant centers in the USA and 138 centers in Europe in 26 countries. Every 30 minutes one of parenchymal organs such as liver, pancreas, kidneys, lungs or heart is transplanted all over the world.
In Poland the first unsuccessful attempts at orthotopic liver transplantation were made in 1987 by prof. Stanislaw Zielinski and his team from the Department of Surgery, Pomeranian Medical University in Szczecin (patien died 2 weeks after OLTx). The first successful procedure was performed in a child, in 1990, in The Children's
Memorial Health Institute in Warsaw. 1994 was the real turning point for Polish liver transplantology. In the Department of General, Transplant and Liver Surgery, Medical University of Warsaw the first successful orthotopic liver transplantation was performed in a female patient with PBC. She is Polish longest-surviving patient (16 years now) with a good chance of many more years to live. In the following years a team of surgeons, anesthesiologists and pathologists were trained in France in two leading transplant centers - one run by prof. Henry Bismuth in Villejouif near Paris and the other in L'Hopital Cochin in Paris run by prof. Didier Houssin.
However, it was not until 1999 when the liver transplant program was well developed. Until June 2010 we perfomed 805 OLTx and 50 reOLTx. The best results, regarding the number of transplantations, were obtained in 2008. The total of 106 patients received OLTx that year which made our Department one of the six first liver transplant centers in Europe.
At the moment in Poland there are 4 centers
© T. Wroblewski Liver transplant program in Poland
Indications for OLTx
Q Chronic liver diseases
s Benig diseases
Fig. 1. Indications for OLTx in Department of General, Transplant and Liver Surgery, Warsaw Medical University
for adult liver transplant and 1 for children. They are:
1. Department of General, Transplant and Liver Surgery, Warsaw Medical University, Banacha, 1a str., 02-097 Warsaw
2. Departament of General and Transplant Surgery, Warsaw Medical University, Institute of Transplantation, Nowogrodzka 59 str, 02-006 Warsaw
3. Departament of General and Transplant Surgery SPSK im. A. Mieleckiego, Silesian Medical University, Francuska 20-24 str, 40-027 Katowice
4. Deapartment of General and Transplant Surgery, Division of Liver, Pancreas and Biliary Surgery, Regional Hospital, Arkonska 4 str., 71-455 Szczecin
5. Department of Pediatric Surgery and Organ Transplantation The Children's Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw
The Department of General, Transplant&Liver Surgery is recognized for its extensive influence in
hepatic surgery and transplantology in Poland. 250 liver resections and nearly 100ts OLTx are performed there annually. In 1999 the first successful orthotopic liver transplantation from a related donor (LDLT) took place. The procedure was developed by surgical team from our Department supervised by prof. Marek Krawczyk. Two left segments were harvested and the implantation was performed in the Children's Memorial Health Institute in Warsaw under the supervision of prof. Piotr Kalicinski. This is the only program of such kind in Poland. As Poltransplant data show it covers 50% of pediatric demand for transplantation. Annually 20 organs from a living-related donor are harvested for children and up till now 147 procedures of this type have been performed. This year we are celebrating the 10th anniversary of LDLT introduction.
Unfortunately, despite the growing number of OLTx, the waiting list continues to expand on a yearly basis. This proves the demand for transplantation is constantly increasing. (Fig. 1) At the end of 2009, 183 people were registered on the liver transplant waiting list while 224 transplantations were performed. In comparison, in 2007, 178 OLTx were performed and the number of patients awaiting transplantations equaled 182. (Tab.1)
1. Indications for OLTx
Generally, indications for OLTx include:
• chronic, advanced and incurable liver diseases;
• acute liver failure;
Table 1
National Transplant Waiting List (2009) Poltransplant Information Buletin 1(18)[March 2010]_
Ö n oi n oi e £ n oi n oi n oi n oi g n ul n oi r
Waiting for kidney transplantat r rof hn d § « tat tna Waiting for es tat tna Waiting for kidney and tat tna Waiting for liver transplantat Waiting for heart transplantat Waiting for lung tat tna Waiting for d n tat tna e h t e
.f ES ag, lp s n a £ e u u n es a lp s n a £ lp s n a £ lp s n a £ a t r a e -= lp s n a £ g © t ^
January** 1501 14 1 123 215 31 18 1903
February** 1512 11 1 125 207 35 18 1909
March** 1532 11 1 147 195 33 18 1937
April** 1544 14 1 139 201 34 18 1951
May** 1553 15 1 144 198 34 18 1963
June** 1574 19 2 156 211 35 18 2015
July** 1577 17 2 164 206 34 19 2019
August** 1604 19 2 167 200 35 19 2046
September** 1636 22 2 176 228 37 20 2121
October** 1711 24 3 181 237 36 20 2212
November** 1731 24 4 178 245 36 19 2237
December** 1768 26 3 2 183 253 37 19 2291
• metabolic diseases;
• malignant neoplasms;
• combined liver and other organ transplantation;
• retransplantations.
Covering the period from 1989 (the first OLTx) to 2009, it is clearly visible that hepatitis C has gradually become one of the leading indications for liver transplantation, reaching up to 1/3 of the cases in the recent years.
2. Techniques of orthotopic liver transplantation
At present, two techniques of liver transplantation exist. The conventional Starzl technique with the removal of retrohepatic vena cava and administration of extracorporeal veno-venous by-pass and a piggy-back technique with preservation of the inferior vena cava and side-to-side anastomosis between the recipient vena cava and the retrohepatic vena cava of the graft.
Initially, all patients in the Department were operated on with the Starzl technique. Nowadays we typically use the piggy-back technique and it is principally only for the very selected patients that we employ the conventional technique. We use the latter method in case of:
a) patients without collateral circulation developed (e.g. acute toxic liver failure, hepatitis fulminans);
b) difficult hepatectomies in patients with very well developed collateral circulation, after abdominal and hepatic operations (where the risk of substantial blood loss is very high);
c) liver retransplantation;
d) patients with HCC, with a tumor situated very near the inferior vena cava which forces its removal.
The remaining anastomoses in both techniques are created in a much similar way. After vena cava is anastomosed in an end-to-end fashion, we reperfuse the liver. Following on that, we perform arterial anastomosis and reperfusion. End-to-end bile duct anastomosis is finally performed without any drain.
It is common practice in patients transplanted for PSC, Caroli syndrome and SBC ( secondary biliary cirrhosis) to form a Roux-en-Y jejunal loop. After necessary hemostasis, 3 Redon drains are usually placed to allow active suction. Drains are removed, if possible, in the second or third day after the operation.
Liver cirrhosis
:■: Alcoholic cirrhosis 0 Hepatitis B cirrhosis
0 Hepatitis C cirrhosis Hi Hepatitis B+C cirrhosis
H Cirrhosis of unknown origin a Autoimmune cirrhosis Fig. 2. Indications for OLTx due to liver cirrhosis in the Department of General, Transplant and Liver Surgery, Medical University of Warsaw
Fig. 3. OLTx in patients with C hepatitis
cholestatic diseases
■ secondary biliary cirrliosis B primary biliary cirrhosis S primary cholangitis sclerosans
Fig. 4. Indications for OLTx due to cholestatic diseases in the Department of General, Transplant and Liver Surgery, Medical University of Warsaw
3. Postoperative care
After the transplantation a patient is transported to the surgical intensive care unit. Depending on their general condition and efficacy of breathing, they are either extubated or stay on mechanical ventilation. In case of uncomplicated transplantation, patients are closely monitored for 3 or 4 days and then they are transferred to so called clean surgical unit.
Doppler ultrasound is used to assess hepatic artery flow in the first postoperative day. In case of
© T. Wroblewski Liver transplant program in poland
The num ber of transplantations
780
1989 1993 1994 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009
Fig. 5. The number of cadaver transplantations - the Department of General, Transplant and Liver Surgery, Medical University of Warsaw, SPCSK Banacha (1989-2009).
Age of patients
age from 17 to 67, median age: 43
17 21 25 29 33 37 41 45 49 53 57 61
Age (years)
Fig. 6. Patients aged 17 to 67
120
100
15
0
doubts concerning arterial patency, patients undergo an urgent contrasted CT with hepatic vessels visualization. If the complication is confirmed, a patient is enlisted for identically blood-group matched retransplantation. If a patient's condition deteriorates, which naturally is visible in their biochemical results, they need to be enlisted for ABO-incompatible retransplantation.
For prevention of general infection a patient after an operation receives a broad-spectrum antibiotic called Meronem (AstraZeneca) and immunosuppressive treatment.
At the moment the procedure and immunosupression are of the highest standards and the majority of patients have a very good possibility of living a long life.
4. Results
A total of 805 liver transplantations were performed in the Department between 1989 until end of July 2010.
Technical difficulties occuring in the early postransplant period
l.large haematomas10-15%;
2.hepatic artery thrombosis 2-8%;
3.biliary complications 10-20% of patients out of which 80% in the 1st 3-6 months;
4.portal vein thrombosis 1-3%;
5.hepatic veins thrombosis/ stenosis 0,5-1,7%.
At the moment the results in our Department meet the standards of other centers in Poland and in the world. (Tab. 2, 3). Perioperative mortality rate doesn't exceed 10%, but it is necessary to mention that the results include urgent cases when patients are operated on due to hepatitis fulminans, fungus poisoning or chemical poisoning of different type. While waiting for OLTx, they are treated with albumin dialysis performed with "Prometeus" equipment. In this group perioperative mortality rate rises up to 50%, the result similar to retransplantations.
The most crucial problem of liver transplant centers have to deal with is recurrence of the original disease and the necessity of retransplantation. There have been retransplantations performed in the Department which included patients operated upon urgently for perioperative indications such as hepatic artery thrombosis and recurrence of the previous liver failure in the later period.
42-90% of recipients suffer from HCV (hepatitis C virus) reinfection within 5 years following liver transplantation, 50,0-70,0% present with inflammation of the graft, 15,0-30,0% develop cirrhosis within 5-7 years.
Survival: 1 year= 80,0-94.8% of patients, 3 years
Table 2
Results of cadaver transplantations - all centers in Poland [2]
Survival The number of recipients observed* Recipient survival % Recipient survival Graft survival % graft survival
3 months 1262 1124 89 1101 87
12 months 1185 1024 86 1000 84
36 months 790 648 82 618 78
60 months 414 320 77 296 71
* from 1998
Table 3
Results of cadaver transplantations - the Department of General, Transplant and Liver Surgery, Medical University of Warsaw, SPCSK Banacha [2]
Survival The number of Recipient survival % Recipient survival Graft survival % graft survival _recipients observed*_______
3 months 475 428 90 420 88
12 months 461 404 88 395 86
36 months 283 232 82 222 78
60 months_96_71_74_67_70
* from 1998
= 76,0- 84,1% of patients and 5years = 62,2-75,0% of patients. The necessity for retransplantation has been reported in about 10% of patients within 15 years after OLTx.
PBC (primary biliary cirrhosis) reappears in 25,0-50,0% of patients 10 years after transplantation, 10,0-24,0% of cases require retransplantation.
PSC (primary sclerosing cholangitis) recurrence = 20,0%
HCC (hepatocellular carcinoma) patients constitute a separate group. In our Department we use Milan criteria as the selection for liver transplantation. In this group 1-year survival rate fluctuates from 91,0% to 82,0%, 5-year from 79,0% to 61,0% and 10-year come to 44%. HCC recurs in 5,3% - 20,0% within 5 years from OLTx.
Conclusions
The success of our liver transplant program
determines substantial progress which has been made in preservation of health in Poland in the recent years. The Department of General, Transplant and Liver Surgery of Medical University of Warsaw plays one of the most important roles in this program in both cadaver and living-related donor transplantation.
REFERENCES
1. The Department's data archive
2. Poltransplant Information Buletin. - 2010. - Vol.18, N1.
3. www.poltransplant.org.pl
Contact adress
02-097, Poland, Warsaw, Banacha 1a Katedra i Klinika Chirurgii OgYlnej, Transplantacyjnej i Watroby, Medical University of Warsaw, tel.: +48 22 59-92-543, e-mail: wroblewskitad@tlen.pl, prof. Tadeusz Wroblewski
nocmynuna 8.10.2010 г.
