Carey, Thomas A

Faris, Tanous D

Marchioro, Thomas L

Otte, Jean-Bernard

Starzl, Thomas E

English

PubMed

D-Scholarship@Pitt

AMERICAN MEDICAL WOM€N'S ASSOCIATION Volume 21 March 1966 h'umber 3 I The follocing p~lpers were presented at the 1965 Annual .Meeting, Nove~nber 13, in Chicago. W e  cish to thank Lederle Laboratories for their support.-The Editorc. Thomas E. StarzI, A4.D.. Ph.D.; Thomas L. Marchioro, 1M.D.; Tanous D. Faris. A4.D.; Thomas A. Carey, MD., and Jean-Bernard Otte, A4.D. -4 FEIV TE.IRS AGO it seemed highly unlikely that homotmnsplantation of tissues and or- gans was so soon to play a significant role in the medical armamentarium, despite an enormous quantity of research dating back more than a half century. The view persisted that the severity and perseverance of homo- graft reiection constituted an insurmountable barrier t o  the successful use of alien tissue. Since 1961, these attitudes have undergone a remarkable change. illore than a hundred patients throughout the \vorld have had sjgnif- - *.Aided by Grants AM 06285, .llI 063.F4, HE 07735. AM 07772,  FR 00051, and FR 00069, from the U.S. Public Health Service. icant prolongation of life through functioq- ing renal homografts. Long-term sun-ival has been obtained in laboratory animals after homotransplantation of other organs including the liver, lung, heart, and spleen. Earlier un- warranted pessimism concerning the fate of homografts has been replaced by what, in some circles, may be viewed as overoptimism since the life expectancy of patients or animals n i th  transplants tolerated over a long period of time is not yet known. In this communication, a brief account will be given of the results of clinical renal homo- transplantation a t  the University of Colorado Jledical Center, focusing attention only upon those patients treated from 20 t o  36 months 2 08 JOCRS.-\L OF THE .IAIERICAS XIEDICAL WOR.IES'S ASSOCIATIOS ago. -1 brief description of the encouraging results niter esperimental liver transplantation \\-ill also be included. TABLE I Rrnclts in 64 Conseczctive Patients T r e ~ t e d  with Renal Howlografts Obtained from Living Volunteer Donors During the lnterval from November 1962 to March 1964; Sunival is to the First Part o f  Decernbt-7. 1965 RENAL HOMOTRANSPLANTATION Sixt!--four consecutive patients were treated with renal homografts from living volunteer donors betlreen November 1962 and March 1964.l.' Rejection was controlled with azathi- oprine (Imuran), prednisone, actinomycin C, and in one case with total body irradiation. The greatest risk from failure due to  homo- graft malfunction or to toxicity from irnrnu- nosuppressive agents is during the first few postoperaave months when variable degrees of rejection are common. The  phenomenon of rejection has proved to be reversible with intensification of immunosuppressive therapy. Later, the aggressiveness of therapy can very often be relaxed; nevertheless, many patients now living for a long time after operation have had continuing evidence of low-grade host-against-graft immunologic activity. The results in these 64 patients are sum- marized in Table I. Thirty-seven (58 per cent) of the 64 patients lived for at least one year after operation. Three subsequently died after 13 1/2, 22, and 23 1/2 months. In all 3 cases, renal function was still suflicient to maintain active life, but other complications of chronic liver injury (possibly drug induced) and sepsis were the direct cause of death. The remaining 34 patients (53.1 per cent) are still alive after 20 to 36 months. Twenty-three of these patients have already passed the 2-year level of convalescence. The  best results were in the 46 cases in which the kidney was provided by a blood relative (Table I). Thirty-one of these pa- tients (67 per cent) lived for at least l year; 30 (65.2 per cent) are still alive with an average survival of 28 months. In contrast, only 6 of the 18 patients (33 per cent) who received kidnevs from nonrelated donors lived beyond 1 year, and 2 have subsequently died. Kidney function is adequate in all of the currently surviving patients although in some there has been a gradual decline in the quality of renal excretion and in others continuous stable function has required the recurrent administration of potentially toxic doses of prednisone. These clinical findings suggest that future death will occur at a gradual rate due to continued low-grade rejection. This impression is strengthened by study (by Dr. Lived Died After No. 1 Year 1 Year Alive Tom1 Series 64 37 3 * 34t Related donors 16 3 1 1 30 Nonrelated donors 18 6 2 6 'Late deaths at 1 3  X, 22, and 23X months. tOf these patients 23 are from 2 to more than 3 years. The other 11 are between 20 and 24 months. Ken A. Porter, St. Mary's Hospital and Medi- cal School, London) of biopsies taken from 21 of the homografts obtained after approxi- mately two years' residence in their human hosts. The  following are some of Dr. Porter's findings. Three of the homografts were normal. In the others, there was an assortment of abnor- malities often not associated with impairment of renal function. There were vascular lesions which had many forms: fibrous intimal thickening of interlobular arteries often with rupture or duplication of the internal elastic lamina; de- position of a hyaline-like substance in the subintimal layer of afferent arterioles; and deposition of the PAS-positive hyaline ma- terial in the glomerular capillaries. The homografts with vascular lesions fre- quently had other secondary morphologic changes: fibrosis of the glomerular tuft, peri- glomerular fibrosis, interstitial fibrosis, or tubular atrophy. In addition, the majority of the homografts contained focal accumulations of mononuclear cells. Ten  to 40 per cent of these cells con- sisted of the pyronine positive variety, which are traditionally found in acute homograft re- jection. In homografts functioning over a period of time such cells seem to be reasonably u-ell-tolerated. HOMOTRANSPLAVTATION OF THE LIVER There are two general methods for whole organ transplantation of the liver. One in- volves the extirpation of the host animal's own liver and replacement with an organ obtained from a nonrelated mongrel animal. The homograft is revascularized in a normal manner. Using immunosuppressive regimens similar to those employed for the kidney, survival in our laboratories has been obtained J.A.M.W.A.-Vcu. 2 1 .  No. 3 THER4PEUTIC POTESTIAL OF ORGAN TRANSPLAXT-STARZL AND OTHERS 209 I for as long as 20  month^.^ Most of the general problems encountered are comparable to  those already well-defined after transplanta- tion of the kidney. In spite of these successful experiments, 7 efforts a t  human orthotopic transplantation in Denver 2nd elsewhere have failed; maxi- mum survival has been 23 days. These experi- ences have defined problems of technique, organ preservation, and control of coagula- tion which must be successfully managed in future trials. An alternative method of liver transplanta- tion, which may some day have application for the treatment of hepatic failure due to benign liver disease, is heterotopic uansplanta- tion.' Here, the host liver is not removed and the homograft is placed in some abnormal location such as the pelvis, left upper quad- rant, or one of the paravertebral gutters. Al- though the concept of heterotopic transplan- tation is an attractive one, since residual func- tion in the host liver is not sacrificed, i t  is still not known whether this approach is a sound one. Recent laboratory investigations have shown that when two livers are present in the same animal each may be responsible for injury to the other, apparently by  a mechanism of competition for nutritional metabolites. Such physiologic problems as well as those con- cerned with the space limitations in a recipi- ent's abdomen make it  necessary to defer judgment about the future potential useful- This is a condensed version of tb ~cientific session-Ed. ness of this approach. Clinical heterotopic transplantation is known to have been attempted in at least 6 institutions, with maxi- mum survival of only 5 weeks. SUMMARY C More than half of an original series of 64 patients receiving renal transplants, treated at the University of Colorado Medical Center from 20 to 36 months ago, are still alive. The  ultimate life expectancy of these remaining patients is not known. Significant improve- ment in results after liver transplantation has been documented in animals, but long-term success has not yet been obtained in patients. REFERENCES 1. Stad .  T .  E.: Experience in Renal Transplanta- tion, W. B. Saunders Company, Philadelphia. 1964. 2. Starzl, T. E.; Marchioro, T. L.; Terasaki, P. I.; Porter, K. A.; Faris, T. D.; Herrmann, T. J.; Vre- devoe. D. L.; Hutt, M. P.; Ogden, D. A., and Wad- dell, W. R.: Chronic survival after human renal homotransplantation, Ann. Surg. 162:749-787, Oct. 1965. 3. Starzl, T. E.; hlarchioro, T. L.; Porter, K. -4.; Taylor, P. D.; Faris. T .  D.; Hemnann, T .  J.; Hlad, C. J., and Waddell, W. R.: Factors determining short- and long-term survival after orthotopic liver homo- transplantation in the dog, Surgery S8: 131-155, July 1965. 4. Marchioro, T. L.; Porter, K. A.; Dickinson, T .  C.; Faris, T. D., and Starzl. T. E.: Physiologic requirements for auxiliary liver homotransplantaaon, Surg. Gynec. 8( Oba. 121: 17-31, July 1965. Le paper presented by Dr. Stan1 at the Dr. Starzl is Professor of Surgery, University of Colorado School of Medicine, and Chief of  Surgery, Veterans Administration Hospital, Denver. Dr. hlarchioro is Assistant Professor of Surgery, University of Colorado School of Medi- cine, Alarkle Scholar; and Assistant Chief of Surgery, Veterans Administration Hospitnl, Denver. Dr. Faris is Instructor in Surgery, University o f  Colorado School of Medicine, and Clini- cal Investigator, Veterans Administration Hospital, Denver. Dr. Cnrey is a Resident and Dr. Otte a Fellow, the Department of Surgery, University of Colorndo School of Medicine, Denver. 

The Therapeutic Potential of Whole Organ Transplantation.

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The Therapeutic Potential of Whole Organ Transplantation.

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