A Report of the Lung Transplantation

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1 A Report of the Lung Transplantation Workshop-1970 Steering Committee: Max J. Trummer, M.D., John R. Benfield, M.D., David A. Blumenstock, M.D., Frank J. Veith, M.D., and Richard M. Peters, M.D. ABSTRACT A workshop on lung transplantation took place in Washington, D.C., on April 5, Its objectives were to define the current state of the art, to delineate unsolved problems, to resolve conflicting data, and to eliminate duplication of effort. We were fortunate to have the enthusiastic participation of a large number of distinguished men, all of whom are important contributors to the field. The material covered by the workshop was considered under four main headings with a session devoted to each. Informal discussion followed a brief summary by the session chairman. This report summarizes the discussions and presents the consensus of the group. L ung transplantation has been the subject of an exponentially increasing amount of investigative effort since the earliest experimental pulmonary lobe transplantations were reported by Demikhov in However, discrepancies have appeared among the published results, and the clinical application thus far has had only limited success. Workers active in the field felt a need to gather together to discuss the problems of lung transplantation, and this desire led to the organization of the 1970 Lung Transplantation Workshop. A list of participants appears at the end of this report, and their valuable contributions are gratefully acknowledged. The Experience with Human Lung Transplantation Chairman: John R. Benfield, M.D. Since the epochal first clinical lung allotransplantation by Dr. Hardy in 1963, twenty-five lung transplantations have been performed on three continents by twenty surgeons. With the exception of the bilateral lung transplantation performed by Dr. Haglin in March, 1970, a review of the worldwide experience has been published [7]. The major cause of failure has been the recipient s own remaining diseased lung. Drs. Ross, Vanderhoeft, and Kahn each resorted to the use of a tracheal divider postoperatively in an attempt to ventilate each lung independently and thereby prevent pro- Supported in part by Bureau of Medicine and Surgery Work Unit No. MR A, Navy Department, and by the Artificial Organs Division, Travenol Laboratories, Inc. Address reprint requests to Dr. Trummer, Mercy Hospital and Medical Center, 4077 Fifth Ave., San Diego, Calif VOL. 12, NO. 4, OCTOBER,

2 TRUMMER ET AL. gressive hyperinflation and herniation of the recipient s own lung across the mediastinum. In 2 other recipients, the transplant became acutely congested as blood flow was diverted to it as a result of the higher vascular resistance of the recipient s own remaining lung. Two additional patients had severe ventilation-perfusion (V/Q derangements resulting from the disparity in mechanics between the transplant and the remaining diseased lung. Pneumonia contributed to failure in 7 patients. It usually was the result of crossinfection from the opposite lung but was viral in origin in 2 instances. Although chronic rejection ultimately doomed the longest survivor, the role of rejection remains uncertain in 9 other patients even after postmortem examination. Emphasis was placed on the lessons learned from this retrospective review. The foremost is the significant role of the recipient s own remaining diseased lung. In at least 9 patients, the remaining lung was seriously detrimental either because of differences in airway mechanics, V/Q imbalance, or as a source of cross-infection. While it is not surprising that pneumonia often was a major factor, it is noteworthy that even a Pseudomonas infection can be treated successfully in the face of immunotherapy. Definitive recognition of rejection has not been possible during life thus far. It is clear that fairly definite rejection crises can be successfully suppressed at least temporarily, as was done three times in Dr. Derom s long-term survivor and once in Dr. Veith s recent patient. Bilateral lung transplantation or heartlung transplantation may be required to eliminate the problems introduced by the remaining diseased lung. The necessity for a short ischemia time reflects the lack of satisfactory methods of organ preservation. INDICATIONS FOR LUNG TRANSPLANTATION Criteria that have been established at Harbor General Hospital in Torrance, California, for the selection of potential recipients are as follows. 1. The patient must show continuous deterioration of pulmonary function in spite of receiving the best care that is available. 2. The patient must require oxygen-enriched controlled ventilation and yet fail to show improvement in blood gases or respiratory mechanics. 3. The patient must have undergone frequent hospitalizations for respiratory failure. 4. The patient and the family must be suitable psychologically for this type of experimental clinical undertaking. REPORTS OF RECENT EXPERIENCE Important innovations and postoperative studies in very recent clinical lung transplantations have yielded sufficiently significant information to warrant brief case reports. Dr. John Haglin reported a bilateral lung transplantation performed in March, 1970, and emphasized the need for reestablishing the bronchial artery circulation. Complications related to the bronchial anas- 348 THE ANNALS OF THORACIC SURGERY

3 Lung Transplantation Workshop tomosis, both experimentally and clinically, have been significant and may justify this emphasis. The recipient was a 49-year-old man with severe chronic obstructive emphysema who had been bedridden for six years and had developed a Pseudomonas and Klebsiella infection in his right lung while awaiting a donor. When a donor became available, the plan was (1) to proceed with transplantation in spite of the infection; (2) to test the value of restoring the bronchial circulation; and (3) to test the ability of one allografted lung to function alone. The patient s right lung was to be removed after the left lung transplantation, and then, if needed, the right lung allograft would also be installed. The left lung transplantation was performed using cardiopulmonary bypass. The bronchial arteries were reconstructed by removing a button of donor aorta that included the origins of these arteries and anastomosing this button to the recipient s aorta. Four hours postoperatively it became apparent that the left lung graft alone was not able to provide adequate pulmonary function. The right lung graft, which had undergone a cold ischemia time of 11 hours, was installed without the use of cardiopulmonary bypass and without restoring the bronchial circulation. The roentgenographic evidence of edema that appeared early postoperatively cleared during the subsequent week. However, there was a severe V/Q defect in both transplanted lungs and a high alveolar-arterial oxygen gradient. Between the third and sixth days the patient did well clinically even though the chest roentgenogram and blood gases were abnormal and he could not be removed from the respirator. On the sixth day, presumptive signs of rejection appeared in the right lower lobe, and despite some response to steroids this process progressively worsened until the patient died on the eleventh day. During the final 2 days he had a Klebsiella septicemia. In spite of a very short donor right main-stem bronchus, anastomotic necrosis with necrosis of the bronchial mucosa distal to the anastomosis was found at postmortem examination. In contrast, the left bronchial mucosa both grossly and microscopically was similar on either side of the anastomosis, with only lymphocytic infiltration of the submucosa. Patency of the left bronchial artery was demonstrated by injection of methylene blue. Bronchial artery circulation unquestionably had been restored to the left anastomotic site. Dr. Lillehei commented on his patient, discussed elsewhere [6], in whom total cardiopulmonary transplantation was performed in December, In this patient, bilateral lung transplantation, with the heart in addition, completely solved the problem of V/Q imbalance which has plagued unilateral lung transplantation in persons with emphysema. Respiratory drive was entirely adequate, proving that a patient with a cardiopulmonary transplant can initiate spontaneous respiration and that such lungs can function. VOL. 12, NO. 4, OCTOBER,

4 TRUMMER ET AL. Dr. Derom reported on his patient who was the longest survivor of lung transplantation to date [3, 41. The factors responsible for the prolonged survival were that the patient had restrictive disease (silicosis) and not emphysema, and that he was only 23 years old. Postoperatively, the recipient s own left lung was demonstrated to be nonfunctioning. True palliation was achieved for ten and one-half months, and instances of rejection were treated successfully, if temporarily. The transplanted right lung alone supported life for many months. Dr. Beall described unusual problems encountered in 2 clinical patients [2]. Infection was a major problem. The first patient died of herpes simplex viral pneumonia. It was postulated that cellular immunity is important in viral diseases and that the first patient was a carrier of the herpes virus, inasmuch as he had a long history of fever blisters. The donor had no such history. At postmortem examination the allotransplanted left lung was found to be massively involved by viral pneumonia while the patient s own right lung was not involved. It was theorized that the recipient had infected the transplanted lung, which had no cellular immunity to herpes. In the second patient the cause of death was infection in spite of the fact that neither steroids nor azathioprine were used. The patient was maintained on mechanical lymph depletion for three months and received antilymphocyte globulin. His ability to fight off foreign tissue was suppressed, but he was able to overcome septicemia from a subclavian vein catheter. His fatal infection came from the donor lung, in which pneumonia progressed to formation of an abscess that ruptured and seeded the remainder of the tracheobronchial tree. Dr. Hardy reported some observations based on his clinical experience. His second patient [51 demonstrated the futility of trying to transplant a lung in a 68-year-old bedridden man who was cachectic and unable to eat or walk. In contrast to the first patient, although the architecture of the transplant in the second patient was well preserved at the time of death at 29 days, the lung had not functioned for several days prior to death. It was very solid, and there was a remarkable exudate into the alveoli. Dr. Hardy suggested that this might have been due to the lung ischemia time of 3 hours in this patient, as compared to only 1% hours in his first patient. Dr. Hardy commented that concurrent diseases must be considered in the selection of potential recipients. What is needed most of all is a set of criteria for determining whether a patient will not live appreciably longer without lung transplantation. At the present time, if the patient s condition will improve on medical therapy he should not undergo lung transplantation. DISCUSSION The points listed below were discussed, and the consensus may be summarized as follows. 1. The criteria for selection of recipients were agreeable to the partici- 350 THE ANNALS OF THORACIC SURGERY

5 Lung Transplantation Workshop pants. An upper age limit of 45 to 50 years was suggested. Infant recipients currently should not be sought, and emphysema patients are less than ideal recipients. Cancer patients perhaps should be excluded. Victims of restrictive pulmonary disease are the most likely candidates. The importance of selection criteria was stressed. 2. It was agreed that cardiopulmonary bypass should be available on a standby basis during unilateral lung transplantation. 3. The need for a long-term auxilliary extracorporeal respiratory support system was reiterated. One investigator suggested that such a system be available before further clinical lung transplant trials are undertaken. 4. The use of related living donors was not endorsed. 5. The question of whether or not to proceed further with human trials was discussed extensively. It was generally agreed that much additional information could be derived from further animal experiments but that the problems encountered in human lung transplantation are different from those encountered in the laboratory. Even primate experiments are not equivalent to human trials. The immunological barriers remain central and of key importance, and studies of this problem in man are more meaningful than are animal studies. Although much data still can be obtained from the laboratory, it was the consensus that clinical lung transplant efforts should proceed. Immunological Features Unique to the Lung Chairman: David A. Blumenstock, M.D. There are several reasons for the failure of lung transplantation to achieve the success rate of kidney transplantation: (1) The pulmonary transplant has proved to be vulnerable to invasive viral and bacterial agents, and present methods of immunosuppression result in an unacceptably high incidence of severe infection in the transplant patient. (2) There is no satisfactory indicator of rejection, and it is difficult to differentiate between graft failure due to infection and that due to rejection. (3) No adequate artificial respiratory support system is available. (4) The unexpected nonimmunological problem of V/Q imbalance between the allograft and the remaining diseased lung has resulted in the failure of several transplantation attempts in man. Because the lack of a satisfactory method of immunosuppression is currently the greatest problem, histocompatibility matching of donor and recipient offers the promise of reducing the amount of immunotherapy required. Recently, the significance of tissue-typing prior to lung grafting itl dogs has been evaluated. In typed, untreated beagles, the survival of the recipient animal was prolonged and rejection of the graft was delayed in comparison with the results following lung allografting in mismatched beagle pairs. Typing has proved less feasible and less reliable in mongrel dogs.

6 TRUMMER ET AL. Although the results are inconclusive, histocompatibility typing is likely to be helpful in transplantation between genetically related pairs. More specific methods of altering the rejection response are needed. While cytotoxic drugs should be investigated, therapy programs must be developed that will prevent allograft rejection without generalized immunosuppression. Biological methods of producing specific immunological tolerance to a foreign graft appear to be the most fruitful area for future research. Although treatment with lymphocytic and lymphoblastic antisera have resulted in increased survival of allografts, these sera also appear to act by a general immunosuppressive mechanism. However, such agents may prove useful as part of a system designed to produce specific immunological tolerance. DISCUSSION Immunosuppressive Therapy in Animals. Dr. Garzon presented the results of treatment in a series of dogs. Azathioprine given in a daily dosage of 6 mg. per kilogram of body weight increased the mean survival to 24 days, and the addition of prednisone further increased it to 62 days. Matching the animals by usual lymphocyte matching tests increased survival to 98 days. Although Dr. Garzon agreed that histocompatibility typing would be of benefit, there was no unanimity of opinion on this subject. Indicators of Rejection. The important problem of identifying rejection was the focus of considerable discussion. Dr. Hutchin reported the use of 133Xe scans and angiograms in a series of unmodified grafts. These were found to correlate well. The total duration of the arterial phase and the venous appearance time were found to be of value in assessing rejection; both were prolonged in autografts and allografts soon after operation, but in allografts the duration of the arterial phase progressively increased, while in autografts no further change occurred. Additionally, during rejection the normal vascular bed was disrupted, beginning with the smallest vessels visible on angiography and progressing until there was no flow through the graft. Although the 133Xe scan had the advantage of simplicity, it was nonspecific in differentiating rejection and vascular occlusion. Dr. Barnes reported a decrease in the V/Q ratio in dogs with allografts during periods of rejection, whereas no change occurred in autografts. Perfusion was found to persist longer than ventilation as the lung was rejected. He suggested that this finding might prove valuable in evaluating rejection. However, Dr. Benfield pointed out that in experimental autotransplants he had found the decrease in V/Q to be greatest on the third postoperative day with the decrease persisting for as long as three weeks. This phenomenon was thought to limit the usefulness of the test. Dr. Beall emphasized that the denervated transplant responds to pneumonia by a decrease in perfusion and a larger decrease in ventilation and that V/Q studies therefore would be of little value in differentiating rejection from infection. The participants generally agreed with this conclusion. 352 THE ANNALS OF THORACIC SURGERY

7 Lung Transplantation Workshop Dr. Fisk discussed animal studies which included alveolar-arterial oxygen (A-a 0,) gradients. The A-a O2 gradient became abnormal with infection or rejection and was altered before the chest roentgenogram became abnormal. He suggested that the A-a O2 gradient might be useful in predicting the early onset of rejection. Pathology of Lung Transplants. Dr. Veith subdivided the findings during rejection into an early, alveolar phase and a late, vascular phase. The vascular phase occurs too late to be of practical value in managing patients. He considered the plain film of the chest to be the most valuable aid in evaluating the recipient. Drs. Veith and Hagstrom had obtained material and reviewed the histological appearance of the transplanted lungs from 23 human patients. The interpretation was inconclusive in 7, but in 16 patients the lung demonstrated proteinaceous material and desquamated alveolar cells in the alveoli. Seven patients demonstrated this histological picture in isolated form. Five other patients had in addition the cellular infiltrate usually associated with rejection. In 7 patients the proteinaceous exudate coexisted with the histological changes of acute pneumonia. Veith termed this picture of proteinaceous material and desquamated macrophages in alveoli atypical rejection. Whether the reaction is immunological was not determined. He also noted that several instances of hyaline membrane formation had been encountered in his review. Repeated needle biopsies of the lung have been of limited value in distinguishing rejection from infection because of the difficulty of interpreting the histological material so obtained. It was recommended, however, that needle biopsies continue to be done as part of the investigative procedure. Antilung Antibodies. Dr. Lillehei noted that antiheart antibodies were present at the beginning of rejection in his heart transplant patients, and he suggested that similar antilung antibodies be searched for as a possible indicator of rejection. Dr. White reported recent studies in which lungs were exchanged between 7 pairs of baboons. Extremely high titers of antilung antibody were found in these animals. Unsolved Physiological Problems of Lung Transplantation Chairman: Frank J. Veith, M.D. The following questions concerning physiology appear to have been tentatively answered. 1. Transplanted lungs can function normally, and a single transplanted lung can provide total respiratory and vascular function at all times after transplantation. It has been known that one transplanted lung could provide total pulmonary function if several months elapsed before ablation of the function of the opposite lung, and more recently it has been shown in dogs, baboons, and man that a single transplanted lung can provide total VOL. 12, NO. 4, OCTOBER,

8 TRUMMER ET AL. respiratory and vascular function beginning immediately after transplantation. 2. In experimental studies, technically perfect venous, arterial, and bronchial anastomoses are essential to normal transplant function. Even technically flawless experimental autotransplants undergo a transient period of decreased function. Thereafter, except for a slightly diminished compliance, they can have almost normal physiological values which do not deteriorate with time. The importance of the left atrial anastomosis has been emphasized for some time. More recently, attention has been directed to the arterial anastomosis as a site of high resistance to flow, especially when the entire cardiac output is forced immediately through the transplanted lung. The importance of a distensible pulmonary artery anastomosis has been emphasized by Veith and supported by Noirclerc and Daicoff. However, the matter is still in dispute. 3. The vasculature of the transplanted lung can dilate with increased flow. The previously held belief that transplanted lungs have a fixed vascular resistance with no ability to vasodilate with increased flows was founded in part on technical and methodological artifacts. However, the evidence is still controversial concerning the ability of denervated or transplanted lungs to vasodilate normally in response to extremely high blood flow. Whatever vascular defect may exist does not appear to be of sufficient magnitude to contraindicate transplantation of a single lung. 4. The denervation of transplanted lungs need not produce an inadequate pattern of respiration. It now has been shown that monkeys, dogs, and man can maintain respiration adequate for survival after denervation, autotransplantation, or allotransplantation of both lungs with or without the heart. 5. Although abnormal lung extract surface activity (surfactant) has been noted in transplanted lungs with venous anastomotic obstruction or during rejection, it is generally believed that surfactant changes are secondary to other alterations and are not of primary significance in determining the outcome of lung transplantation. The following appear to be the principal unsolved physiological problems at this time. 1. What is the relative importance of V/Q imbalances and of rejection in the failure of single lung allografts in patients with emphysema? Should one or both lungs be transplanted in these patients? Several such patients with single lung transplants have been noted to have the bulk of their pulmonary blood flow distributed to the transplant, while the remaining emphysematous lung received the majority of the ventilation or trapped air and by its overdistention compressed the transplant. This imbalance has been thought to be due to the relatively low vascular resistance of the transplant and the relatively high compliance and expiratory airway resistance 354 THE ANNALS OF THORACIC SURGERY

9 Lung Transplantation Workshop of the emphysematous lung. On this basis, it has been advocated that either simultaneous bilateral transplantation should be done or that the contralateral lung should be altered to prevent its overdistention. However, the relative contribution to this imbalance of the physiological setting and of rejection or infection are not known. Recent observations of extensive alveolar exudates in patients who developed this imbalance suggest that the imbalance becomes severe only when the alveoli of the allograft become extensively involved by rejection. 2. Does innervation return to the lung, and to what extent? Although the Hering-Breuer reflex does not appear to be essential to survival in dogs or primates, the return of this reflex provides evidence of functional regeneration of afferent parasympathetic fibers. The return of the reflex has been demonstrated in about 50% of dogs and occurred as early as seven months after reimplantation. Some dogs may never regain the reflex. 3. What is the significance of the interruption of bronchial circulation in lung transplantation? Many workers have observed a high incidence of bronchial leakage or stenosis in both experimental and clinical transplants. Technical precautions advocated to minimize the incidence of these complications include transection of the bronchus as close to its bifurcation as possible, buttressing of the bronchial anastomosis with a flap of viable tissue, and anastomosing a button of the donor aorta containing the origins of the bronchial arteries to the recipient aorta. Dr. Veith s technique has been to invaginate the donor bronchus into the recipient bronchial stump, and in his hands this technique has almost completely prevented bronchial complications in canine transplants. 4. What are the physiological and functional defects produced in the allografted lung by ischemic injury or by rejection? Since human transplant candidates have severe bilateral pulmonary disease, the lung transplant must be able to provide total pulmonary function at all times after its insertion. Therefore, experimental evaluation of methods of immunosuppression or of preservation should be conducted in animals that must rely totally and immediately upon the function of their transplant. DISCUSSION The Responsiveness of the Vasculature of the Grafted Lung. Dr. Ebert reviewed his studies of lung function following autotransplantation and following hilar stripping. The pulmonary vascular resistance (PVR) was observed to rise in both preparations when the entire cardiac output was diverted to the altered lung, whether the experiment was performed immediately or 28 days postoperatively. Dr. Ebert was of the opinion that this change in PVR might not affect survival but suggested that the vasculature of the implant was not normally adaptive. He ascribed the change to denervation rather than to stenosis at the vascular anastomoses. Dr. Trummer reported the results of comprehensive near-simultaneous measurements of multiple pulmonary characteristics in 4 dogs that were

10 TRUMMER ET AL. long-term survivors of left lung autotransplantation and whose postoperative hilar anatomy was normal. The transplanted lung was slightly smaller and less compliant than normal, but its V/Q ratio, diffusion, and airway resistance were normal. Resting hemodynamic data and vascular reactivity, as measured by the response to alveolar anoxia, were normal. However, temporary diversion of the entire cardiac output to the transplanted lung resulted in a rise in PVR, in contrast to a fall in PVR when all the output was shifted to the nontransplanted lung. Dr. White s studies, conducted in baboons, led him also to conclude that denervation was the cause of the abnormal PVR. Dr. Alican recently has successfully reimplanted both lungs in dogs at the same operation [l]. He regarded the anoxia time to which the lung was exposed as one of the critical factors and ascribed the changes in PVR to imperfections in technique rather than to denervation. Regeneration of Bronchial Circulation and Nerves. Dr. Waldhausen noted that by selectively introducing carbon monoxide into hilar-stripped lungs, restoration of bronchial circulation could be detected within 30 days. Dr. Baker s work with reanastomosis of the bronchial arteries in calves led him to conclude that the arteries do not play a significant role in the reimplanted lung. Dr. Edmunds reviewed his elegant studies of mucus transport and bronchoconstriction by means of powdered tantalum bronchography. Since these functions are regulated by efferent parasympathetic fibers, the studies indicated that such fibers regenerate within three to six months after reimplantation of the lung. One of 11 dogs demonstrated return of the peripheral bronchial cough reflex ten months after reimplantation. The clinical significance of these findings in relation to their role in reducing the ability of the transplanted lung to defend itself against infection remains to be determined. The Potential Implications of Lung Transplantation Chairman: Richard M. Peters, M.D. DISCUSSION Lung Preservation. Dr. Fisk described a method of perfusing isolated lungs which has been used at the University of Alberta for the past four years. The lung is placed in a chamber and ventilated by negative pressure, the left atrial (venous) pressure is maintained at 4 mm. Hg to preserve capillary hemodynamics, the lung is perfused with homologous blood, and a whole animal is used as a biological filter and to deoxygenate the blood. With this technique, a lung routinely could retain normal pulmonary function values for 12 hours without focal lesions, hemorrhage, or edema. This ex vivo system was recommended as a simple method for evaluation of lungs which previously had been stored by other techniques. Dr. Peters commented that the implications of these studies were most applicable to the problem 356 THE ANNALS OF THORACIC SURGERY

11 Lung Transplantation Workshop ot managing the human donor following neurological death or cardiac arrest. Should extracorporeal pumping be attempted, using the donor as his own biological filter? Dr. Garzon recalled his experience with preservation of lung autografts for 24 hours by cooling and hyperbaric oxygenation. Some animals have survived now for four years with compliance, diffusion, and hemodynamic values equal to those of lungs reimplanted without preservation. However, the animals receiving stored lungs incurred a 50% mortality compared with 15% for simple reimplantation, and pulmonary edema was the usual cause of death. Based upon his experience, Dr. Gag0 also was pessimistic about hyperbaric, hypothermic preservation. Immediate Functional Adequacy of Transplanted Lungs. Dr. Trummer presented a preliminary report of 4 dogs that were first subjected to a left pneumonectomy and then two months later were placed on cardiopulmonary bypass while the remaining right lung was reimplanted. One dog survived for 32 hours. At 24 hours his Pa02 was 59 mm. Hg while breathing room air, and it rose to 450 mm. Hg with 100% oxygen. The Problem of Transplantation for Chronic Obstructive Pulmonary Disease (COPD). Dr. Peters noted that the retained diseased lung has a high compliance and a high vascular resistance. While it would be desirable to retain this lung as a runoff for part of the pulmonary circulation, hyperexpansion of the lung would have to be prevented, perhaps by means of an artificial limiting membrane or by fixation of the mediastinum. Dr. Jenkins pointed out that patients with COPD generally are beyond the recommended age limit for transplantation, with the exception of those with alpha-l-antitrypsin deficiency. Lung Transplantation for Mucoviscidosis. The lethal nature of mucoviscidosis in adolescents makes it reasonable to study the possible application of lung transplantation in such patients. Dr. Schuster pointed out, however, that the problems of infection, possible extension of the metabolic defect to the transplant, and involvement of the entire exocrine glandular system make these patients unlikely candidates for lung transplantation in the near future. Summary of Workshop It was the consensus among the participants that the workshop had achieved its primary objectives and that it had allowed an exchange of ideas among investigators. Future workshops should be scheduled periodically as the field of lung transplantation develops. References 1. Alican, F., Cayirli, M., Isin, E., and Hardy, T. D. One-stage replantation of both lungs in the dog. J.A.M.A. 215:1301, Beall, A. C., Jr., Jenkins, D. E., Weg, J. G., Stevens, P. M., Noon, G. P., John-

12 TRUMMER ET AL. son, P. C., Bell, R. L., Knight, J. V., Rossen, R. D., Butler, W. T., Douglas, R. G., Jr., Williams, T. W., Lewis, J. M., Morgen, R. O., MacIntyre, R. S., Anderson, M. S., Balsaver, A. M., and De Bakey, M. E. Human lung allotransplantation: Report of two cases. Amer. J. Surg. 119:300, Derom, F. Discussion of Hardy [ Derom, F., Barbier, F., Ringoir, S., Rolly, G., Versieck, J., Berzsenyi, G., Raemdonck, R., and Piret, J. A case of lung homotransplantation in man (preliminary report). Nederl. T. Geneesk. 25: 109, Hardy, J. D., Alican, F., Moynihan, P. C., Timmis, H. H., Chavez, C. M., Davis, J. T., Jr., and Anas, P. A case of clinical lung allotransplantation. J. Thorac. Cardiovasc. Surg. 60:411, Lillehei, C. W. Discussion of Wildevuur [ Wildevuur, C. R. H., and Benfield, J. R. A review of 23 human lung transp!antations by 20 surgeons. Ann. Thorac. Surg. 9:489, Lung Transplantation Workshop Participants WILLIAM E. ADAMS, M.D. OTTO GAGO, M.D. W. SPENCER PAYNE, M.D. Chicago, Ill. Ann Arbor, Mich. Rochester, Minn. FIKRI ALICAN, M.D. ANTONIO A. GARZON, M.D. DAVID V. PECORA, M.D. Jackson, Miss. Brooklyn, N.Y. Richmond, Va. R. ROBINSON BAKER, M.D. JOHN J. HAGLIN, M.D. RICHARD M. PETERS, M.D. Baltimore, Md. Minneapolis, Minn. San Diego, Calif. BENJAMIN A. BARNES, M.D. JACK w. c* HAGSTRoM, M.D. JAMES J. RAMS, M.D. Boston, Mass. Cleveland, Ohio Lexington, Ky. ARTHUR C. BEALL, JR., M.D. JAMES D' M'D* SAMUEL R. SCHUSTER, M.D. Houston, Tex. Jackson, Miss. Boston, Mass. CHARLES L. HUANG, M.D. EDWARD J. BEATTIE, JR., M.D. STEWART M. SCOTT, M.D. Baltimore, Md. New York, N.Y. Oteen, N.C. PETER HUTCHIN, M.D. JOHN R. BENFIELD, M.D. San Diego, Calif. KENNETH SERKES, M.D. Torrance, Calif. Morton Grove, Ill. DANIEL E. JENKINS, M.D. DAVID A. BLUMENSTOCK, M.D. Houston, Tex. RICHARD L. SIMMONS, M.D. Cooperstown, N.Y. WILLIAM L. JOSEPH, M.D. Minneapolis, Minn. ARTHUR D. BOYD, M.D. Bethesda, Md. DAVID B. SKINNER, M.D. New York, N.Y. DONALD R. KAHN, M.D. Baltimore, Md. LAWRENCE BRETTSCHNEIDER, Madison, Wis. GARY H. STEVENS, M.D. Cdr, USN (MC) MARVIN M. KIRSH, M.D. Los Angeles, Calif. Bethesda, Md. Ann Arbor, Mich. TIMOTHY TAKARO, M.D. PETER E. BRUECKE, M.D. C. WALTON LILLEHEI, M.D. Oteen, N.C. Boston, Mass. New York, N.Y. MAX J. TRUMMER, M.D. &DO R. CASTANEDA, M.D. RICHARD R. LOWER, M.D. San Diego, CAif. Minneapolis, Minn. Richmond, Va. FRANK J. VEITH, M.D. CECIL M. COUVES, M.D. GEORGE J. MAGOVERN, M.D. Bronx, N.Y. Edmonton, Alta., Canada Pittsburgh, Pa. JOHN A. WALDHAUSEN, M.D. GEORGE R. DAICOFF, M.D. NAEL MARTINI, M.D. Hershey, Pa. Gainesville, Fla. New York, N.Y. WATTS R. WEBB, M.D. FRITZ DEROM, PROF. DR. NOEL L. MILLS, M.D. Syracuse, N.Y. St. Denijs-Westrem, Belgium New York, N.Y. JOHN J. WHITE, M.D. PAUL A. EBERT, M.D. DONALD L. MORTON, M.D. Baltimore, Md. Durham, N.C. Bethesda, Md. L. HENRY EDMUNDS, JR., M.D. THOMAS F. NEALON, JR., M.D. R' wllcox' M'D' San Francisco, Calif. New York, N.Y. Chapel Hill, N.C. ROBERT G. ELLISON, M.D. WILLIAM E. NEVILLE, M.D. MARK W. WOLCOTT, M.D. Augusta, Ga. Hines, Ill. Washington, D.C. L. PENFIELD FABER, M.D. MICHEL J. NOIRCLERC, M.1). WALTER G. WOLFE, M.D. Chicago, Ill. Marseilles, France Durham, N.C. R. LEICHTON FISK, M.D. ARTURO P. NORICO, M.D. JOHN E. WOODS, M.D. Edmonton, Alta., Canada Baltimore, Md. Rochester, Minn. 358 THE ANNALS OF THORACIC SURGERY

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