Surgery Today Jpn. J. Surg. (1992) 22:297-300

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SURGERYTODAY

© Springer-Verlag 1992

Living Related Liver Transplantation MASATOSHI MAKUUCHI, 1 HIDEO KAWARAZAKI, TADASHI IWANAKA, 2 NAOSHI KAMADA,3 TADATOSHI TAKAYAMA,4 a n d MASAMITSU KUMON5 1First Department of Surgery, Shinshu University, School of Medicine, 3-1-1 Asahi, Matsumoto 390, Japan

z Department of Pediatric Surgery, Universityof Tokyo, Faculty of Medicine,Tokyo, Japan 3Department of Experimental Surgery, National Children's Medical Research Center, Tokyo, Japan 4Department of Surgery, National Cancer Center Hospital, Tokyo, Japan ~Noshi Central Hospital, Kohchi, Japan

Abstract: Liver transplantation from a brain death donor has not yet been accepted in Japan. The only alternative method at present is transplantation from a living donor. After the first successful living related liver transplantation was performed by Strong in Brisbane, Australia, Japanese hepatic and transplant surgeons also began to perform such operations. As of February 1991, 16 living related liver transplantations had already been performed in Japan, mainly for children with biliary atresia. Five of these patients subsequently died, however, our patient has survived more than 1 year, and she is presently leading a normal school life. The most important issue regarding living related liver transplantation is to ensure the donor's safety. For this purpose, we conducted a preoperative banking of the donor's own blood and plasma. In addition, a selective vascular occlusion was carried out to reduce blood loss during the resection of the liver. Intraoperative color Doppler ultrasonography was introduced for evaluating the circulation of the graft. By using this modality, the following three points were able to be accurately estimated in order to obtain optimal graft perfusion: 1) The most suitable position for the graft to be fixed to the abdominal wall, 2) whether or not the abdominal wall could be closed and 3) the indication for a ligation of the collateral veins to form a porto-systemic shunt. Thanks to these procedures, living related liver transplantations have now become an acceptable transplant method, however, a transplantation from a cadaver that is brain dead but still has a beating heart is still absolutely necessary for adult recipients. Therefore, in the future, both methods should be performed.

liver transplantation, living donor, warm ischemia, reduced size graft Key Words:

Reprint requests to: M. Makuuchi This report is the gist of a paper read at the 91st Annual Meeting of the Japanese Surgical Society, Kyoto, Japan, 1991 (Received for publication on April 10, 1991; accepted on May 1, 1992)

Introduction

In Japan, brain death is not commonly nor officially accepted definition of death. Even when the family offers to donate the liver from a donor who has died due to a traffic accident, the chief public prosecutor normally does not allow a donor operation to be performed until the heart has stopped beating. Just such a situation occurred in March 1991. It is a surprising and shameful dilemma but such is the present state of affairs in Japan. To avoid this problem and still save patients with end-stage liver failure, the only other choice of therapy is a living related liver transplantation. For a pediatric patient, the adult liver is too large to be put in the small children's abdominal cavity. Moreover, the number of donors for small children is scarce both in Europe and the United States. To overcome this problem, a new technique called a reduced size liver transplantation was invented by Bismuth and Houssin in Paris in 1984 (Table 1). 1 In this operation, the right lobe of the liver is resected and the left lobe is then transplanted with the same vascular pedicles as in an orthotopic liver transplantation, with the major problem being to stop the bleeding from the raw surface of the liver after the recirculation of the graft. Pichlmayr et al. in Hannover carried out the first split liver transplantation in 1988. 2 One liver was split into right and left lobes and the two grafts were then transplanted into two recipients. In this operation, the vascular pedicles of one graft were the same as in an orthotopic liver transplant but those of the other graft were short and small in caliber and were missing the inferior vena cava (IVC). Therefore, highly complicated surgical techniques and two excellent surgical teams were required. This procedure is quite difficult but appears promising for resolving the problem of the shortage of donors. In Japan, such an operation is actually impossible at public universities and national hospitals because all operating rooms are occupied in

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Table 1. History of partial liver transplantation Author Year City Operative procedure Bismuth Pichlmayr Raia Strong

1984 P a r i s Reduced size 1988 Hannover Splitliver 1989 SiloPaulo Partialliver transplant from living related and volunteer 1990 Brisbane Livingrelated

Table 2. History of living related liver transplant in Japan Date Chief Institution Nov. 13, 1989 Jun. 15, 1990 Jun. 19, 1990 Jan. 17, 1991

Nagasue Ozawa Makuuchi Ohta

ShimaneUniversity Kyoto University ShinshuUniversity Tokyo Women's Medical College

the daytime and only one nursing team stays at night. In 1989, Raia in S~o Paulo did two partial liver transplantations from a living donor, one was from a mother and the other from a volunteer, using the banding technique for the donor's liver resection) Both patients died soon after transplantation. Moreover, transplantation from a volunteer was strongly criticized from an ethical point by Strong et al. 4 In the same year, Strong successfully performed a living related liver transplantation from a Japanese mother to her son. 4 At that time, no one had ever performed a liver transplant in Japan, so that the news of a successful liver transplantation from a living donor made a big impact on Japanese liver and transplant surgeons.

however, is still alive 1 year after transplant, and is leading a normal life. This patient is now the longest survivor in Japan. In January 1991, Professor Ohta's team at Tokyo Women's Medical College also performed this operation. All four groups are staffed by experienced hepatic surgeons whose personal experience of hepatic resection number more than 300. As of February 1991, 16 living related liver transplantations have been carried out in our country. Twelve of them were for biliary atresia, 2 for Budd-Chiari syndrome, and one each for cirrhosis and cirrhosis with hepatocellular carcinoma. Kyoto University has done ten transplants, we at Shinshu University three, Tokyo Women's Medical College two, and Shimane one. All donor operations have been performed without either mortality, major complications, or massive bleeding, so that the donor operation poses little ethical problem as long as it is performed by skilled hepatic surgeons. Five recipients died from 21 to 285 days after operation due to rejection followed by infection, cardiopulmonary insufficiency, and probably the side effects of immunosuppressants. Our second patient developed diffuse large cell malignant gastrointestinal tract lymphoma characterized by a monoclonal B-cell Kappa proliferation after FK 506 therapy. 5

Our Techniques for Safer Liver Transplants In order to make partial liver transplantations safer, we have developed new methods for the donor operation and have also introduced intraoperative color Doppler ultrasonography.

The Japanese Experience On November 13, 1989, Professor Nagasue and his colleagues in Shimane Medical University performed the first living related liver transplantation in our country (Table 2). This patient was a 1-year-old boy with biliary atresia. A rupture of esophageal varices had happened during the preoperative examinations and an emergent transplantation was conducted. The transplantation was successful but the bile duct of the left lateral segment was ligated and the ensuing obstructive jaundice was treated by percutaneous biliary drainage. In June 1990, Professor Ozawa's group at Kyoto University and our group in Shinshu University performed the second and third Japanese living related liver transplantations, respectively. These were successfully performed and the patients were both eventually discharged from the hospital. The second case, performed at Kyoto University, died 6 months after transplant due to unknown causes. The third case,

New Techniques for Donor Operation To protect donors from viral infection and to further ensure the donor's safety, a reduction in the amount of bleeding during the liver resection of the donor is essential. For this purpose, the donor's own blood and plasma were banked during the preoperative preparations and approval should be obtained from the ethical committee. As for surgical techniques, the selective vascular occlusion technique of the left medial segment, the modified method of hemihepatic vascular occlusion technique, 6 and the umbilical fossa division technique were applied. In children around 6 years old, a graft larger than the left lateral segment is required. The entire draining area of the left hepatic vein was then identified by intraoperative ultrasonography. All of the left hepatic venous branches which drain the left medial segment were traced to the periphery and these distal points,

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M. Makuuchi et al.: Living Related Liver Transplantation GOT itJ/I 500 400'

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Fig. 3. Serum GOT value after a partial liver transplantation from a living donor in a Japanese monkey. GOT, glutamic oxaloacetic transaminase; ¢, death Fig. 1. Liver anatomy of the left lobe and division line (dotted line). IVC, inferior vena cava; MHV, middle hepatic vein; LHV, left hepatic vein; UP, umbilical portion of left portal vein

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Fig. 4. Postoperative changes of serum GOT values after living related partial liver transplantation using the selective vascular occlusion technique of the left medial segment. GOT, glntamic oxaloacetic transaminase

Fig. 2. Silastic cast of the liver. Arrows indicate Cantlie's line, curved arrows point out the falciform ligament, and arrowheads are the right margin of the draining area of the left hepatic vein

where the venous branches disappear on the sonogram, were then marked by electrocautery on the surface of the liver (Fig. 1). Fortunately, the portal pedicles of the left medial segment branch radially from the umbilical portion of the left portal vein. This division line of the left medial segment was supported by a study on Silastic casts of the liver (Fig. 2). 7 Warm ischemia is " t a b o o " in harvesting. Many efforts to shorten the warm ischemic time have been made for the purpose of maintaining the viability of the graft. In transplantation from a living donor, the donor

has no liver damage. A very short time of ischemia such as ten minutes, will thus not produce any harvesting injury. To evaluate this hypothesis, an experimental study using Japanese monkeys has been conducted. 8 The left hepatic artery and portal vein were isolated and taped. Under a hemihepatic vascular occlusion of the left lobe, the liver was divided in the quadrate lobe. During the division of the liver parenchyma, 10 min of vascular occlusion followed by 5 min of perfusion were repeated. The recipient's liver was totally removed preserving the IVC in situ. The graft was transplanted to the right diaphragmatic space using a shunt tube between the portal vein and the IVC which was passed through the hepatic portion of the cava. The post transplant serum glutamic oxaloacetic transaminase ( G O T ) levels did not increase more than 500 IU/1 while the levels on the second day after transplantation were lower than 200 IU/l (Fig. 3).

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In h u m a n beings, the safest procedures were then selected. The middle hepatic artery and left portal vein were occluded. The arterial blood supply to the ~eft lateral segment was preserved. This method was applied to the first and second donors. Just after transplant, the m a x i m u m serum G O T values 459 and 258IU/1 were recorded but then decreased rapidly to less than 100 IU/l within two days (Fig. 4). In patients whose branching site of the middle hepatic artery was behind the umbilical portion of the left portal vein, the umbilical fossa was divided and all portal and arterial branches to the left medial segment were ligated and divided. By this procedure, the left medial segment was discolored. Next, the liver was divided 5 m m to the right of the left margin of the ischemic area along the falciform ligament. This operation was carried out on the third donor. The blood losses during the donor operations a m o u n t e d to 640,530, and 1130ml, respectively. Only fresh frozen plasma of 400 and 600 ml were transfused in the first and second donors, and 400ml of whole blood and 260ml of fresh frozen plasma were transfused in the third donor. All blood and plasma originated from the donors themselves.

Conclusions

Intraoperative Color Doppler Ultrasonography

References

Intraoperative ultrasonography is indispensable for hepatectomy. 9'1° This technique was used in the donor operations to estimate the division line of the liver. In the recipient operation, intraoperative color D o p p l e r ultrasonography also provides valuable information. Immediately after reperfusion of the graft, the blood flow of vessels of the graft were evaluated. When the size of the partial liver graft is smaller than the recipient liver, the accurate positioning of the graft is important to avoid any kinking of the hepatic vein. The best position to fix the graft with the falciform ligament can therefore be easily estimated by color D o p p l e r ultrasonography. In small children less than two years old, even a segmental graft is often too large to properly close the abdomen. The third case was an 18-month-old boy and just after the abdominal wall was closed, color signals in the portal vein could not be recognized, and thus the abdominal wall had to be re-opened and Ladd's procedure was carried out while monitoring the blood flow in the portal vein. If intraoperative color D o p p l e r ultrasonography had not been applied, then portal vein thrombosis would have occurred in the early postoperative days. At Kyoto University, the blood in the portal vein regurgitated due to a thick hepatofugal collateral circulation. These collateral veins around the spleen were then ligated and a normal hepatopetal flow was obtained in the main portal vein. ~1

1. Bismuth H, Houssin D (1984) Reduced-size orthotopic liver graft in hepatic transplantation in children. Surgery 95:367-378 2. Pichlmayr R, Ringe B, Gubernatis G, Hauss J, Bunzendahl H (1988) Transplantation of one donor liver to two recipients (splitting transplantation): A new method for further development of segmental liver transplantation. Langenbecks Arch Chir 373:127-130 3. Raia S, Nery JR, Mies S (1989) Liver transplantation from live donors. Lancet 2:497 4. Strong RW, Lynch SV, Ong TH, Matsunami H, Koido Y, Balderson GA (1990) Successful liver transplantation from a living donor to her son. N Engl J Med 322:1505-1507 5. Kitahara S, Makuuchi M, Kawasaki S, Ishizone S, Matsunami H, Kamada N, Kawarazaki H, Iwanaka T (1991) Lymphoproliferative disorders after FK506. Lancet 1:1234 6. Makuuchi M, Mori T, Gunv6n P, Yamazaki S, Hasegawa H (1987) Safety of Hemihepatic vascular occlusion during resection of the liver. Surg Gynecol Obstet 164:155-158 7. Kumon M, Yamazaki S, Kawasaki H, Ogata T (1985) Liver segmentation depending on the cast study. In: Ota Y, (ed) Advances in gastroenterology 1985 (in Japanese). NihonIgakkan, Tokyo, pp 28-30 8. Kawarazaki H, Iwanaka S, Nakajo T, Hashizume K, Tanaka K, Utsugi T, Kanamori Y, Makuuchi M, Ishizone S, Hori T, Chen CL, Okada Y (1990) Experimental study and clinical experience of partial liver transplantation from the living donor (in Japanese). Gekashinryo (Surgical Treatment) 32:1733-1743 9. Makuuchi M, Hasegawa H, Yamazaki Y (1981) Intraoperative ultrasonic examination for hepatectomy. Jpn J Clin Oncol 11:367-390 10. Makuuchi M (1987) Abdominal intraoperative ultrasonography. Igaku-shoin, Tokyo 11. Moriyasu F, Someda H, Kawasaki T (1990) Intraoperative application of Doppler ultrasound examination to liver surgery. Jpn J Med Ultrason [Suppl II] 17:15-18



In Japan, living related liver transplantation is at present the only acceptable way to save end-stage liver failure patients. However, such a transplantation for adult patients would be difficult due to the smallness of the partial liver graft. Establishing the upper limit of the ratio between the body weight of the recipient and the graft is now a serious and urgent problem. On June 14th, a special committee organized by the Prime Minister accepted the concept of brain death and a t e m p o r a r y report on this matter was published. Transplantation from brain dead cadaveric donors with beating hearts will therefore soon begin in our country. H o w e v e r , considering the cultural background of our country, the n u m b e r of brain death donors will likely be limited as in K o r e a and Taiwan. Therefore, it is believed that living related liver transplantations will continue to be a m a j o r transplantation procedure and that this operative modality will continue in the near future.

Acknowledgments. This work was supported in part by an Award from the Uehara Memorial Foundation and a grant (03404037) from the Ministry of Education, Science and Culture of Japan.

Living related liver transplantation.

Liver transplantation from a brain death donor has not yet been accepted in Japan. The only alternative method at present is transplantation from a li...
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