TUESDAY AFTERNOON, April 26, 1983

2:00 p.m. Forum Session - Grand Ballroom

25. Atypical Carcinoids of the Lung

RAO R. PALADUGU*, LOUIS F. DECARO*,

RAYMOND L. TEPLITZ*, HYUN Y. PAK*,

LOVISATTI LEONARDO* and JOHN R. BENFIELD

Duarte, California; Verona, Italy

Biological behavior and morphology of pulmonary carcinoids is not constant; management is controversial. We shall define characteristics of car-cinoid (C) and atypical carcinoid (AC) tumors, based on new knowledge that increasing nuclear DNA content correlates well with progressive steps of lung carcinogenesis, and on electron microscopic comparative studies.

Findings in 24 patients (17 or 71% C; 7 or 29% AC) were reviewed:

Microscopic similarities between AC and small (oat) cell cancers were observed.

Nuclear DNA measurements by image analysis were made on 2609 cells, including 216 normal bronchial cells, 1645 oat cells, 399 cells from C and 344 AC cells. Normal bronchial cells were diploid (n = 1.15 ± 0.24) as were C cells (n = 1.12 ± 0.19). AC cells had 1.27 ± 0.73 DNA units and oat cells were essentially tetraploid (n = 1.94 ± 0.73). The DNA content of AC was greater than C (p<0.001). The DNA content of AC was less than small undifferentiated (oat) cell cancers (p<0.001).

We conclude that AC behaves like common bronchogenic cancers, and the morphology of AC has features of oat cell cancers. Nuclear DNA content is a clinically relevant measurement with the potential to help differentiate AC from other carcinoids and from oat cell cancers based on preoperative percutaneous needle aspirates.

*By Invitation

26. Neovascularity of a Tracheal Prosthesis/Tissue Complex

RONALD J. NELSON, LISE GOLDBERG*,

RODNEY A. WHITE*, EDWIN SHORS*

and FRANK M. HIROSE*

Torrance, California; Seattle, Washington

Permanent bioincorporation of a microporous tracheal prosthesis will require a stable blood supply to connective tissue supporting an epithelial surface. In experience with over 80 tracheal implants in dogs we have observed that 1) end-on ingrowth and epithelialization does not occur in the absence of lateral ingrowth, 2) epithelialization is marked by the appearance of a subepithelial network of vessels, and 3) this process must be well advanced by 6-8 wks. for long term stability. These observations were extended using microangiography to delineate the blood supply of the prosthesis/tissue complex.

Six implants of bioelectric polyurethane with 10% Gentamicin (3 cm. length, 2 cm dia., 1-1.25 mm. wall thickness, 60-120 µmicropore dia.) were interposed in the dog thoracic trachea and wrapped with an omental pedicle. The aorta was perfused with a barium suspension at elective sacrifice between 10 wks. and 22 mos. Radiographs of specimens were correlated with bronchoscopic, gross and histopathologic findings.

Neovascularity to the prosthesis/tissue complex can be described in three categories: outer capsule (OC), prosthetic wall (PW), and inner lining (IL). OC vessels were oriented circumferentially immediately adjacent to the prosthetic wall and extended up to the length of 180° cross-sections. They resembled arteries up to 75 µ dia. on microscopy and appeared to originate in the omentum with connections developing to the bronchial circulation. PW vessels up to 75 µdia. with thin muscular walls were noted to traverse the porous wall. The IL had subepithelial longitudinal vessels up to 120 µdia. linking tracheal and prosthetic networks across the anastomoses. We conclude the omentum provides an immediate blood supply oriented circumferentially adjacent to the wall and a base for early connective tissue ingrowth. Epithelialization occurs as early as 3 wks. on this favorable bed accompanied by vascular connections to the existing lamina propria tracheal vessels. This dual organization is probably important to long term stability.

*By Invitation

27. Single Lung Transplantation with Cyclosporine Immutio-suppression

STEPHAN L. KAMHOLZ*, FRANK J. VEITH,

FRED P. MOLLENKOPF*, KENNETH L. PINSKER*,

RONALD R. KALEYA*, ALLEN J. NORIN*,

MARVIN L. GLIEDMAN*. EUGENE E. EMESON*,

AVRAHAM D. MERAV*, RICHARD BRODMAN*,

STANLEY C. FELL and CHERYL M. MONTEFUSCO*

New York, New York

Cyclosporine (Cy), a potent new immunosuppressive agent, was used (alone or in combination with other drugs) in 28 canine single lung allograft (SLA) recipients. Mean recipient survival with good SLA function was 144 days with Cy and far exceeded that obtained in previous SLA recipients treated with standard immunosuppression (11 days). The results of these experiments showed that: (1) 20% of the recipient animals exhibited no evidence of rejection whatsoever, one of these animals survives over 2½ years with normal allograft function and morphology; (2) 75%of the animals exhibited some evidence of rejection that was easily reversed in 76% of instances with corticosteroids. Over 50% of these animals exhibited good lung allograft function 6 months or more after surgery. (3) Rejection in these animals was characterized by more prominent vascular involvement (demonstrated on open lung biopsy and by decreased blood flow on nuclear perfusion scan) than that which occurred in SLA recipients treated with standard immunosuppression. (4) Diagnosis of rejection in Cy treated lung allograft recipients was made by microscopic analysis of sputum and analysis of the cellular content of bronchoalveolar lavage samples coupled with deterioration of pulmonary hemodynamics and decreased perfusion on ⁹⁹Tc lung scan. (5) Successful and complete healing without stenosis of the bronchial anastomosis occurred in 80% of the animals studied.

These findings have been corroborated in two human Cy treated SLA recipients, one of whom survives 4 weeks after transplantation and 2 weeks after contralateral pneumonectomy. This overall experience indicates that Cy, although not a perfect immunosuppressive agent, increases the likelihood of success with therapeutic single lung transplantation.

*By Invitation

Scientific Session - Grand Ballroom

28. Powerful but Limited Immune Suppression for Cardiac Transplantation with Cyclosporin A and Low Dose Steroid

HARTLEY P. GRIFFITH*, ROBERT L. HARDESTY*

and HENRY T. BAHNSON

Pittsburgh, Pennsylvania

Seventeen of thirty patients have survived a new trial of cardiac transplantation to evaluate Cyclosporin A and prednisone (15 mg.) alone for immune suppression (range 1 to 19 months). The low dose of prednisone was chosen to lessen steroid morbidity, and other immunosuppressive drugs (ATG, azathioprine) were avoided to reduce the risk of infection and lymphoma. Rejection was graded as moderate with focal myocyte necrosis and as severe with general myocyte necrosis. Both moderate and severe rejection were treated with 1 gm. pulses of cortisone, usually for 3 to 5 days without alteration of the prednisone dose.

Death occurred in 2 patients with mild rejection (1 stroke, 1 pneumonia); 3 with moderate rejection (2 stroke, 1 abdominal infection); and in all 7 patients with severe rejection (2 patients with acute rejection and 1 with acute rejection and infection less than 5 weeks postoperatively, and 4 with chronic rejection and restrictive cardiomyopathy). Two of the four patients with restrictive cardiomyopathy succumbed from coronary atherosclerosis.

Seventy-seven percent of all patients treated have been judged to have adequate immune suppression. Pulse therapy with cortisone was effective in all but those with general myocyte necrosis. Cardiac catheterization in 9 patients surviving greater than 10 months has documented adequate graft function (cardiac index 2.5, ejection fraction 52%). Infections have been rare and side effects of steroids minimal; one patient died following the development of a polyclonal Epstein-Barr lymphoma.

This trial suggests that Cyclosporin A and prednisone is superior immune suppression for cardiac transplantation, but patients with advanced stages of rejection should be treated with an additional immunosuppressive agent. Subsequent to this analysis, 5 patients have been treated during rejection episodes with ATG, and in all further myocyte necrosis was eliminated.

2:45 p.m. Intermission - Visit Exhibits - Lower Level

(Galleria) - Complimentary Coffee

*By Invitation

3:30 p.m. Scientific Session - Grand Ballroom

29. Reoperation on Prosthetic Heart Valves

DAVID G. HUSEBYE*, JAMES R. PLUTH,

JEFFREY M. PIEHLER*, HARTZELL V. SCHAFF*,

THOMAS A. ORSZULAK*, FRANCISCO J. PUGA*

and GORDON K. DANIELSON

Rochester, Minnesota

Five-hundred-and-twenty-nine patients underwent reoperation for prosthetic valve dysfunction during the years 1961-1980. Included were 391 patients with aortic valves, 107 with mitral valves, 12 with tricuspid and 19 with double valve reoperations. Surgery was elective in 235, urgent in 263, and emergent in 31. At the time of reoperation, 82 patients were Class I (NYHA), 156 Class II, 200 Class III, and 91 Class IV. Ten percent of patients with heterografts or disk valves required emergency reoperation as compared to 5.4%with ball valves and 0%with homograft valves. Thirty percent of patients with disk valves were Class IV compared to 20% for heterografts, 14% for homografts and 7.5% for ball valves. Twenty-three patients had complications related to sternal reopening including lacerations of the right atrium (5), right ventricle (7), aorta (9), and division of a previous coronary graft in 2. Two deaths resulted from these complications. The risk of reoperation for aortic valve was 1.3% for Class I patients, 1.6% for Class II, 6.3% for Class III and 20.8% for Class IV. For mitral valves, the risk was 4% for Class II, 9.3% for Class III, and 41% for Class IV. Based on urgency of operation, the operative risk for elective aortic valve replacement was 1%, urgent 8%, and emergency 37.5%. Corresponding figures for the mitral valve were 0%, 20%, and 55%. Risk was highest for infective endocarditis and for patients undergoing disc or heterograft valve replacement. At five years following valve reoperation, 75% of the patients were surviving. Survivorship of patients who were Class I or II at the time of second operation was 85% and identical to patients undergoing initial valve replacement. Survivorship for Class III and IV patients was significantly decreased. This study indicates that if valve repair or replacement is necessary, it should be done early and electively before functional cardiac deterioration occurs.

*By Invitation

30. Mitral Reconstructive Surgery: A Series of 130 Consecutive Cases

ARRIGO LESSANA *, TU TRAN VIET*,

FRANCOIS ADES*, SAID MOSTEFA KARA*,

ABDERRAHMAN AMEUR *, FRANCOISE HERREMAN*

and MICHEL DEGEORGES*

Paris, France and Oran, Algeria

Sponsored by: R.W.M. PRATER, Bronx, New York

Between January 1975 and January 1982, 130 patients (pts) underwent mitral valvuloplasty (MV) for pure or predominant mitral insufficiency (MI). Mean age at operation was 30 ± 17 years. 25 pts were under 15 years of age. MI was mainly (111/130) due to rheumatic disease. 59 pts (45,4%) had another valve disease which necessitated a surgical correction (tricuspid 36, aortic 23).

Surgical technique for MV varied according to the lesions. 2 pts only had an isolated annuloplasty (AN). The remaining 128 (with 125 AN) can be divided in 3 groups. Group I (35 pts) in which MI was due to restricted amplitude of valve motion, was treated by mobilisation of the leaflets by resection of basal chordae, with or without fenestration of the chordae and/or commissurotomy. In group II (48 pts) in which MI was due to chordal elongation and valve prolapse, correction of MI consisted in chordal shortening, and/or partial resection of the prolapsed leaflet. In type III (45 pts), both mechanisms were responsible for MI and both types of MV were associated according to the lesions.

Three pts died in the first month after surgery (2,3%). 5 pts are lost to follow-up. Mean follow-up period for the 122 remaining pts is 38 months ± 27. 7 pts had to be reoperated and 2 of them died. An additional pt died without reoperation. Late mortality was therefore 3/122 (2,5%).

Almost all (117/119) the remaining pts are in class I (105) or II (12) of the NYHA. There is no residual murmur in 29 pts. A trivial systolic murmur is found in 61 pts. In only 6 pts was there a loud residual systolic murmur. Mean cardio-thoracic ratio decreased from 60,6% ± 7,7 preoperatively to 53,7% ± 6,2 postoperatively (p<0.001). Thromboembolic episodes were noted in 4 pts, all of them in atrial fibrillation. Actuarial curves including hospital mortality show a 91,3% survival rate at 7 years, an 87,4% embolus-free rate at 7 years and a 92,5% absence of reoperation at 6 years. There was no significant difference between the results of the groups I, II and III. Although the mean follow-up period of this series is only of 38 months ± 27, these results show that even complex procedures of MV can provide stable functional results, low surgical and late mortality, together with an acceptable rate of reoperations.

*By Invitation

31. The Hancock Conduit: A Dichotomy Between the Late Clinical Results and the Late Catheterization Findings

SCOTT STEWART, PETER HARRIS*,

JAMES MANNING* and CHLOE ALEXSON*

Rochester, New York

Eighteen patients received a Hancock valved conduit as part of their corrective operation for complex congenital heart disease between 1974 and 1977. Seventeen patients survived operation. We had concern for the long-term durability of the conduit. Therefore, a postoperative protocol was established to evaluate each patient clinically every 6 to 12 months and, in addition, to perform a follow-up catheterization study at both 1 and 5 years after operation. Fifteen patients have had a good to excellent longterm clinical result while only two have had a poor result.

Each surviving patient has undergone several routine serial follow-up catheterization studies. The results of these studies are in direct contrast to the excellent clinical results. One year after operation the mean trans-conduit gradient had increased from 16 mm Hg. at the time of operation to 25 mm Hg. Two of 16 patients (12%) had a gradient exceeding 50 mm Hg. Five years after operation the mean gradient had increased to 40 mm Hg. and 6 of 15 patients (40%) had a gradient in excess of 50 mm Hg. Each of those patients with a significant conduit gradient were considered to have had a very satisfactory result by clinical evaluation.

Five patients (30% of all those followed 5-8 years) have undergone replacement of an obstructed conduit without mortality and with satisfactory resolution of the gradient. Each of the excised conduits have shown varying degrees of internal fibrous peel formation and valve degeneration.

This experience emphasizes the dichotomy between an apparent good clinical result with the Hancock conduit and the tendency for a significant late pressure gradient to develop across it. Late catheterization studies must be performed in all patients with this conduit (not just in those in whom a pressure gradient is clinically suspected) since obstruction of the conduit does occur in the presence of a clinically good result.

*By Invitation

32. Early Experience with the Ionescu-Shiley Pericardial Xenograft Valve-Accelerated Calcification in Children

WILLIAM E. WALKER *, DAVID A. OTT*,

JAMES J. LIVESAY*, GEORGE J. REUL*,

J. MICHAEL DUNCAN* and DENTON A. COOLEY

Houston, Texas

Current selection of a valve prosthesis depends on a choice between the durability of mechanical valves and the low incidence of embolic problems with tissue valves. Accepting the IS valve as suitable for adults, we hoped that it would also be good for children, who have difficulties with anticoagulation and who have shown a tendency to early calcification of porcine valves. This review outlines our disappointing experience in children.

Over the period 1978-1982, 2167 consecutive patients survived placement of 2372 IS valves in the left heart. Of 30 valves implanted in children 16 years of age and younger, 6 (20%) have already required replacement because of severe calcification. There has been no known embolic episode in children, no valve has become infected, and there has been no valve leaflet disruption, a complication we have seen with three mitral implantations in adults. No teenager over sixteen years of age has developed significant calcification so far, and only two adults have had their prosthesis replaced because of calcification.

While the Ionescu-Shiley valve has good hemodynamics in small sizes, and a low incidence of embolic complications, it appears to have an unacceptably high incidence of calcification in children. We believe this is more frequent in post-pubertal than in pre-pubertal children, and we have seen no calcification in children over sixteen years at the time of implantation, but it is too early to say that this valve is satisfactory in some children, and we again use mechanical valves in childhood.

4:45 p.m. Executive Session (Members Only)

Grand Ballroom

7:00 p.m. President's Reception

Empire Room - Twin Towers Complex

*By Invitation