TRANSPLANTATION AND CLINICAL IMMUNOLOGY. Proceedings of the Twenty-Second International Course, Lyon, May 1990

Size: px

Start display at page:

Download "TRANSPLANTATION AND CLINICAL IMMUNOLOGY. Proceedings of the Twenty-Second International Course, Lyon, May 1990"

Audrey Howard
5 years ago
Views:

1 ~ Reprinted frm: TRANSPLANTATION AND CLINICAL IMMUNOLOGY VOLUME XXII Multiple Transplants Prceedings f the Twenty-Secnd Internatinal Curse, Lyn, 2-23 May 99 This publicatin was made pssible by a grant frm the Fndatin Merieux Editrs: J.L. Turaine J. Traeger H. Betuel J.M. Dubernard J. P. Revillard C. Dupuy ~ 99 EXCERPTA MEDICA, Amsterdam - New Yrk - Oxfrd

2 99 Elsevier Science Publishers B.V. (Bimedical Divisin) Transpl::mtatin and clinical immunlgy XXII. J.L. Turaine et al. eds. 9 PRESENT STATUS OF THE CLUSTER TRANSPLANTATION AND ITS VARIANTS Mari Alessiani, M.D., camill Ricrdi, M.D., satru Td, M.D., Andreas Tzakis, M.D., Jhn Fung, M.D., Ph.D., Thmas E. starzl, M.D., Ph.D. Frm the Department f surgery, university Health Center f pittsburgh, University f pittsburgh, and the Veterans Administratin Medical Center, pittsburgh, Pennsylvania. INTRODUCTION Upper abdminal exenteratin with rgan transplantatin has been used t treat a selected grup f patients with nn-resectable upper abdminal malignancies (). exenteratin, mst f the structures deriving frm with the embrynal fregut are remved, allwing ptentially cmplete circumscriptin f certain hepatic, bile duct cell, dudenal, gastric and pancreatic malignancies which may have spread t the surrunding lymph ndes r adjacent rgans. the PATIENTS AND METHODS The rgans excised are the liver, pancreas, spleen, stmach, dudenum, and variable prtins f the prximal cln. The rgans replaced are variable. Three different transplantatin replacement techniques have been used: liver-pancreas-dudenum "en-blck" (riginal cluster) (), liver nly (mdified cluster) (2), and liver-pancreatic islets (3). Original Cluster, (Grup ) Twenty ne patients were treated with the riginal cluster prcedure between July 988 and January 99 (grup ). The indicatins are shwn in Table. The patients were beynd help with cnventinal treatment, and in mst f them resectins, chemtherapy, irradiatin, r cmbinatins f these mdalities already had been tried. The first 5 patients f this grup had

3 2 immunsuppressin with cyclsprine, OKT3 inductin with a 5 r day curse, and prednisne t which azathiprine was added if needed. In the ther 6 patients the immunsuppressin was with FK 56 and sterids (4,5). Mdified Cluster, (Grup 2) Eighteen patients had the same exenteratin but with liver placement nly between April 989 and December 989. All the patients except ne were treated with the same cyclsprine ccktail used in the first 5 patients f Grup. The exceptinal patient was treated with FK 56 and sterids. The tumr diagnses are shwn in Table 2. Liver-Islets (Grup 3) After abdminal exenteratin, these 9 patients had liver replacement and pancreatic islet transplantatin (3) under FK 56 and sterids between January 99 and April 99. OKT3 was given if necessary t cntrl rejectin. The tumr diagnses (Table 3) were similar t thse in Grups and 2. RESULTS Grup After t 29 mnths f fllw-up, 8 f the 2 patients are alive (38%) and 6 f them (28.5%) are free f recurrence (Table ). Seven f the 9 deaths resulted frm technical cmplicatins and infectins, usually at an early time. Tumr recurrence ccurred later and was respnsible fr 6 deaths (Table metastases beynd the peratin. ). Tw resectin f these margins at patients had the time f The best survival was f patients with sarcmas and neurendcrine tumrs, and the prest with duct cell carcinmas. psitive lymph ndes in the specimen was a pr prgnstic finding.

4 2 TABLE Primary Pathlgy Alive NED AWD DOD 7 Duct Cell CA 4 Carcinid 3 Sarcma 2 Chlangi CA 2 HCC Adenca Gallbladder Adenca Cln Neurendcrine TABLE --- Survival by diagnsis in the riginal cluster patients (Grup ). NED = n evidence f disease, AWD = alive with disease, DOD = dead f disease. Grup 2 with a fllw-up ranging between 2 and 2 mnths, 6 patients are alive (33%) and 4 f them (22%) are free f recurrence. The causes f death, time f death, and prgnstic influence f tumr diagnsis were n different than in Grup (Table 2). As in Grup, sme patients (2 examples) had metastatic tumrs beynd the resectin margins at the time f peratin but this was nt appreciated until later. TABLE 2 Primary Pathlgy Alive NED AWD DOD 9 Chlangi CA HCC 5 Carcinid Leimysarcma Neurendcrine TABLE Survival by diagnsis in the mdified cluster patients (Grup 2). Fr legend, see Table. Grup 3 six f the 9 patients are alive after 8 t mnths f fllw-up. One patient died f recurrent cancer after 78 days, and 2 thers died earlier frm infectin; all three were insulin dependent at the time f death. Of the 6

5 22 patients wh are alive, 4 are withut evidence f tumr recurrence and all 6 are insulin free. Table 3 shws the survival by tumr diagnsis. TABLE 3 Primary Pathlgy Alive NED AWD DOD 2 chlangi CA Adenca Pancreas 2 HCC Sarcma Adenca Cln Neurendcrine TABLE 3 Survival by diagnsis in the liver and pancreatic islet patients (Grup 3). Fr legend, see Table. DISCUSSION These peratins had a high mrtality frm technical cmplicatins which always led t infectins. In Grup recipients, the pancreas cmpnent f the graft was respnsible fr 4 fatal cmplicatins: pancreatitis and pancreatic abscess (2), and pancreatitis and rupture f an arterial pseudaneurysm (2). Severe weight lss was bserved in patients f all 3 grups and thse in Grups 2 and 3 required prlnged parenteral hyperalimentatin (in sme t the present time). handicap f being diabetic. Grup 2 patients had the further Cntrl f this cmplicatin in Grup 3 patients by islet transplantatin was ntewrthy. The use f FK 56 seemed t make the cntrl f rejectin easier, but the case material was t limited and cmplex t allw cmparisns with cyclsprine ccktail regimens. Patients treated with FK 56 (6 in Grup, ne in Grup 2, and 9 in Grup 3) had very lw sterid requirements cmpared t thse treated with cnventinal immunsuppressin. Acute rejectin usually culd be reversed with a blus f methylprednislne and increased dses f FK 56. In an FK patient f Grup I, graft versus hst disease (GVHD) was unequivcally diagnsed with sex kharytyping

6 23 perfrmed by in situ hybridizatin f the Y chrmsme; the dnr was a male and the recipient female. She was treated successfully with increased sterid therapy. The type and the extent f tumr were the chief nntechnical factrs influencing later survival. Patients wh had macrscpic r micrscpic lymph-nde invlvement had a very high rate f recurrence. Hwever, ur experience suggests that a selected grup f patients culd benefit frm this radical surgical apprach. Afterwards, adjuvant chemtherapy r irradiatin shuld be cnsidered. The nutritinal prblems suffered by patients in all 3 grups (especially Grups 2 and 3) suggest that future trials may require the additin f a gastric cmpnent t the replacement graft. This wuld have t be placed in mainstream cntinuity with the alimentary tract. Such new ptins may becme feasible with the better immunsuppressin made pssible with FK 56 (4,5). REFERENCES. Starzl TE, Td S, Tzakis A, et al: Abdminal rgan cluster transplantatin fr the treatment f upper abdminal malignancies. Ann Surg 2: , Tzakis AG, Td S, Starl TE: Upper abdminal exenteratin with liver replacement: A mdificatin f the "cluster" prcedure. Transplant Prc 22: , Tzakis AG, Ricrdi C, Alejandr R, et al: Pancreatic islet transplantatin after upper abdminal exenteratin and liver replacement. Lancet 336: 42-45, Starzl TE, Td S, Fung J, Demetris AJ, Venkataramanan R, Jain A: FK-56 fr human liver, kidney and pancreas transplantatin. Lancet 2:-4, Td S., Fung JJ, Starzl TE, et al: Liver, Kidney and Tracic Organ transplantatin under FK-56. Ann Surg 22 (3): , 99.

THROUGH 1979, immunosuppressive

THROUGH 1979, immunosuppressive Five-Year Survival After Liver Transplantatin THROUGH 1979, immunsuppressive therapy fr liver transplantatin at ur center was with aathiprine (r cyclphsphamide) and sterids, t which antilymphcyte glublin