TUESDAY AFTERNOON, May 8, 1990

1:45 p.m. SCIENTIFIC SESSION - Sheraton Ballroom

20. Surgery for Limited Small Cell Lung Cancer: The University of Toronto Lung Oncology Group Experience

FRANCES A. SHEPHERD*, ROBERT J. GINSBERG,

RONALD FELD*, WILLIAM K. EVANS* and

ELSE JOHANSEN* Toronto, Ontario, Canada

Since 1977, 119 patients with limited SCLC have undergone including surgery at our institution. Seventy-nine patients (58 male, 21 female; median age 63) had surgery first, and 67 of these had adjuvant chemotherapy. Forty (27 male, 13 female; median age 59) had chemotherapy first and 94% achieved complete or partial response before surgery. Pre-treatment staging revealed 69 stage I, 27 stage II, and 23 stage III tumors. Twenty-six patients required pneumonectomy, 88 lobectomy, and 5 had no resection. Four patients had gross and six had microscopic residual disease. Post-operative pathology showed SCLC only (95), non-SCLC (3), mixed (17), and no residual tumor (4). Post-operative staging revealed 35 state I, 36 stage II, and 48 stage IIIa. The median survival of the entire group is 111 weeks and projected five year survival 39"%. No survival difference was seen between patients treated with chemotherapy before surgery and those undergoing initial surgery followed by chemotherapy (p=0.756). The median survival for pathologic stage I patients has not been reached, and the projected five year survival is 51%. This is significantly better than stage II (median 82 weeks, p=0.001) or stage III (median 83 weeks, p=0.001) patients who have projected five year survivals of 28% and 19% respectively. Seven of the 12 patients who had no adjuvant chemotherapy remain alive 6+ to 48+ months. Sixty-seven patients have died (11 were NED). Only 10 patients relapsed in the primary site alone, seven at the primary and distant sites, and 39 only in distant sites.

In summary, resection improves control at the primary site, and a significant proportion of patients with stage I (NO) disease achieve long-term survival and cure with combined modality therapy including surgery. Stage II and IIIa patients have survival predictions similar to equivalent stage non-SCLC carcinoma treated surgically.

*By Invitation

21. The Response of Pulmonary Vascular Resistance to Cardiac Transplantation

JAMES K. KIRKLIN, ROBERTO. SOURCE*,

DAVID C. NAFTEL*, DELORES MASON* and

ANDREW E. EPSTEIN*

Birmingham, Alabama

Elevated pulmonary vascular resistance (PVR) is a known risk factor for early death from acute right ventricular failure following orthotopic cardiac transplantation (C Tx). Patients with an elevated PVR due primarily to increased left atrial pressure ("reactive") frequently have normalization of PVR following transplantation, but few studies have detailed the time course and magnitude of these changes. To analyze the response of PVR to C Tx, data from 3,574 right heart catheterizations on all 161 patients undergoing cardiac transplantation between 1981 and January 1, 1989 were analyzed. Before transplantation 16% of pts. had a PVR ≥ 4 Wood Units (WU), 21% a pulmonary artery systolic pressure (PA Sys) ≥ 60 mmHg, and 25% a transpulmonary gradient (TPG; PA mean - pulmonary capillary wedge pressure) > 12mmHg.

In the overall group, PVR decreased within 1 week (wk) (2.65 WU ± 0.19 pre-Tx vs 1.43 WU ± 0.07 at 1 wk, p(paired t-test) < 0.001) and was essentially unchanged at one year (p = 0.6). PA Sys fell within 1 wk (50mmHg ± 1.5 vs 29mmHg ± 0.66, p < 0.0001) with a further decline at 1 year (p<0.001). TPG did not significantly change postoperatively.

Among the 15 patients with a pre-Tx PVR >4.0 WU (range 4.0 - 11.3, mean 5.79 ± 0.61) the PVR was greatly reduced among surviving patients at 1 wk (n = 13, 5.79 ± 0.61 vs 1.91 ± 0.19, p<.0001) without further change at 1 year (p= .11). Similar changes were noted in PA Sys (60mmHg ± 3.7 vs 33mmHg ± 2.4, p = .0003) but changes in TPG were likely due to chance (17 ± 2.5 vs 10 ± 0.78, p = .9). Comparing the high PVR group (>4 WU) to the low PVR group (<4 WU), PVR remained slightly higher in pre-op high PVR patients at 1 wk (1.8 WU ± 0.24 vs 1.4 WU ± 0.10, p = .07) and 1 month (1.9 WU ± 0.19 vs 1.4 WU ± 0.46, p = .02), but differences at 1 year were likely due to chance (1.9 WU ± 0.34 vs 1.4 WU ± 0.1,p=.11).

Inferences

* As a group, C Tx recipients have a normal PVR, PA Sys and TPG within 1 wk after C Tx with little change thereafter for at least the first year.

* Surviving patients with elevated pre-Tx PVR, PA Sys, and/or TPG undergo near normalization of these parameters within 1 wk of transplantation.

* Patients with "reactive" elevation of PVR are likely to survive orthotopic C Tx if appropriate preservation of the RV is accomplished and support techniques are available if necessary for about the first wk following C Tx, after which a nearly normal PVR can be expected.

*By Invitation

22. Monitoring of Mononuclear Cells from Coronary Sinus Blood and Right Atrium in Patients Following Heart Transplantation

CHRISTOPH HOLZINGER *, ANDREAS ZUCKERMANN*,

RAINALD SEITELBERGER*, GUNTHER LAUFER*,

AXEL LACZKOVICS* and ERNST WOLNER

Vienna, Austria

In the present study we investigate, whether patterns of mononuclear cell (MNC)-subpopulation isolated from coronary sinus blood (CS) in patients following cardiac transplantation undergo changes during graft-rejection.

79 endomyocardial biopsies (EB) in 36 patients were performed. Grading of graft rejection was classified by the Billighamscheme. 32 biopsies showed grade-0, 33 a mild grade-1 and 14 a moderate grade-2 rejection.

After EB, heparinized blood samples were withdrawn from right atrium (RA) and the CS. Grade-0 and -1 EB showed no difference between the patterns of MNC-subpopulation from CS- and RA- blood. In the CS blood, however, a significant, 1.56 fold, increase of MNCs was assessed. Grade-2 rejections showed a 4.2 fold augmentation of MNC in the CS. In addition T helper/inducer increased from 27.1% in RA and to 41.2% in SC, natural killercells (NK) from 17.7% to 31.8% and the Interleukin-2-receptor bearing cells from 6.6% to 15.3%, respectively. Pan-T cells, T cytotoxic/suppressor cells and monocytes did not show any statistically significant changes in their percentage.

These findings correlated with grading according to EB. In two patients EB showed a mild rejection, which was not treated specifically. One patient died of autopsy-confirmed acute rejection soon after EB and the other patient recovered after administration of OKT3 moab.

The accumulation of mononuclear cells (MNC) in the graft and the reaction of the antigen recognizing cells with the foreign tissue, leads to changes in MNC-count and to differnt patterns of MNC subpopulations isolated from coronary sinus (CS) blood than those in the right atrium (RA). Consequently, immunologic changes caused by heart rejection can be detected by comparison of MNC from CS to cells from RA.

EB is the best proven method in diagnosing acute graft rejection. The most important disadvantage is the fact that EB allows only an examination of a rather small area of the heart. However, local discrepancies of immunological reactions in the heart may sometimes lead to false gradings of rejections and focal rejections may even be missed or understated.

In contrary, CSIM allows an excellent survey of the immunological situation of the whole heart. Preparation and examination of EB takes at least 6 hours, whereas the results of CSIM are available within one to two hours. Consequently, adequate antirejection therapy can be started earlier. EB and CSIM are both invasive methods and their combination delivers an excellent insight into immunological processes during heart rejection and acceptance.

INTERMISSION - VISIT EXHIBITS

*By Invitation

3:30 p.m. SCIENTIFIC SESSIONS - Sheraton Ballroom

23. The Effect of Muscle Sparing Versus Posterolateral Thoracotomy on Pulmonary Function, Muscle Strength and Postoperative Pain

STEPHEN R. HAZELRIGG*,

RODNEY J. LANDRENEAU*. THERESA M. BOLEY*,

MEREDYTH L. PRIESTMEYER*, RICHARD A.

SCHMALTZ*, WEERACHAI NAWARA WONG*,

JOSEPH T. WALLS* and JACK J. CURTIS

Columbia, Missouri

We conducted a prospective, randomized, blinded study of 35 consecutive patients to compare the standard posterolateral (SP) thoracotomy to that of the "muscle sparing" (MS) thoracotomy with respect to pulmonary function, shoulder strength and range of motion and postoperative pain. Pulmonary function was evaluated with FEV, and FVC measured preopera-tively, at one week and one month postoperatively. Shoulder strength and range of motion were measured at these same time intervals. Width of thoracotomy opening, postoperative narcotic consumption and wound complications were recorded. Pain was quantitated by use of a visual analogue scale (VAS) obtained every six hours for two days and then every twelve hours for a total of seven days. This was augmented by the McGill Pain Questionnaire which was administered at one week and one month postoperatively. Length of hospital stay and mortality were also examined.

The extent of lung resection was comparable in the two groups (p = .975). Although the MS group required an additional 10 mins. to enter the chest, total operative time was not significantly different. The opening (maximal) width of the rib retractor was comparable between groups (p = .7064). There were no significant differences in pulmonary function, range of motion, or shoulder strength between the groups at one week or one month. There was significant improvement in comfort in the MS group at 48 hours postop (Mean VAS: MS = 33.1, SP=16.5; p = .0498) and for days 3 through 7 postop (Mean VAS: MS = 56.2, SP =43.8; p = .0022). This finding was reinforced with a suggestion of less narcotic requirement by the MS group in the postoperative period (Mean morphine use: MS = 22mg, SP = 35mg; p = .07). Length of hospital stay and mortality were not significantly different between the groups. Incisional seromas developed in 3/16 (19%) of patients in the MS group and 0/19 in the SP group.

In conclusion, there does not appear to be a functional difference between the muscle sparing or standard posterolateral thoracotomy. Patient comfort does appear to be superior with the muscle sparing technique.

*By Invitation

24. Single Lung Transplantation - Alternative Indications and Technique

J. KENT TRINKLE, JOHN H. CALHOON*.

CHARLES L. BRYAN*, WILLIAM J. GIBBONS*,

DAVID J. COHEN* and FREDERICK L, GROVER

San Antonio, Texas

Ten patients had a single lung transplant (SLTX) since March 1988 with one early and one late death and no bronchial complications. One patient had primary pulmonary hypertension, two had secondary pulmonary hypertension and two had COPD due to an Alpha I antitrypsin deficiency - each of which was previously thought to contraindicate SLTX. The other five had various types of restrictive lung disease. Several bedridden patients on preoperative Prednisone underwent successful operation. The only absolute contraindications to SLTX were infection or a life-limiting systemic disease. Cardiovascular dysfunction and cachexia uniformly resolved postoperatively. Donor selection was based on a PO₂/FIO₂ greater than 300, chest circumference ± 10 cm, clear chest x-ray, negative sputum gram strain and 4 hr estimated ischemic time. Harvest technique included donor PGE, 500 µg and pulmonoplegia with cold modified Eurocollins solution. The heart and lung were separated in situ rather than removing a heart-lung block. A telescoping bronchial anastomosis was performed with 4-0 Prolene (NOT absorbable sutures) without an omental wrap. PEEP, Pavulon and Lasix were used to minimize the postoperative reperfusion response especially in patients with pulmonary hypertension. Corticosteroids were not withheld pre or postoperatively. Postoperative immunosuppression included OKT₃, Methylprednisolone and Prednisone, followed by Cyclosporine and Imuran or postoperative day #8. Dyspnea on exertion without a productive cough or fever suggested rejection which was confirmed by desaturation during exercise oximetry. We conclude that SLTX has evolved into a simple operation which requires meticulous pre an postoperative care. It can be performed on a wide spectrum of critically ill patients, not just those with pulmonary fibrosis, with a relatively low morbidity and mortality.

*By Invitation

25. Contribution of the Bronchial Circulation to Lung Preservation

JOSEPH LoCICERO*, MALEK MASSAD*,

JUN MATANO*, RODNEY GREENE*, MARC DUNN*

and LAWRENCE L. MICHAELIS

Chicago, Illinois

Short preservation time still severely limits lung transplantation. To determine the effect of bronchial arterial (BA) flush preservation we studied 54 dogs using the isolated perfused working lung model. Following intact animal baseline measurements, lungs were flushed with lactated Ringer's solution (60ml/kg at 8°C; 250ml/min at ISmmHg) by one of three methods: pulmonary artery (PA) perfusion, BA through a 15cm closed aortic segment, or simultaneous PA + BA. These groups were further subdivided and tested after 0, 4 or 17 hrs of cold storage at 4°C (n = 6 each). Lungs were ventilated (140ml/kg/min @ FIO₂ = 0.21) and continuously reperfused with nor-mothermic deoxygenated autologous blood in a closed loop. Measured variables were: hemodynamics, aerodynamics, leukocytes in bronchoalveolar lavage, and shunt fraction. Survival time was determined from initial reper-fusion to failure of the lung to oxygenate. After 0 and 4 hrs storage, there was no significant difference in survival times. At 17 hrs, PA + BA lungs survived longer than PA or BA alone (120 ±24 vs 38 ±14 or 52 ±16 min; p<0.01). PA pressure and resistance in all groups, except at failure, were never different intact animal baseline. Shunts in PA ± BA groups were closest to baseline at outset (12 ± 5% vs 13 ±4%)and remained lower throughout reperfusion than PA or BA alone. After 17 hrs, static compliance of PA lungs worsened compared to baseline (1.1 ± 0.2E-2 vs 3.2 ± 0.7E-2 L/cm H₂O/sec; p<0.05) while PA + BA remained constant (3.6 ± 1.5E-2L/cm HiO/sec). Likewise, elastic work significantly decreased with time for PA group over baseline (225 ± 46 vs 394 ± 84g-m/min; p<0.05). Bronchoalveolar lavage in PA + BA after 17 hrs demonstrated leukocyte counts similar to intact lungs (45 ± 5 vs 29 ± 8/mm³) and significantly less than PA or BA (137+18 or 82±10/mm^! respectively). We conclude that simultaneous PA + BA perfusion is superior to PA or BA perfusion alone in preserving lungs for extended storage. This may also be achieved by core cooling of the donor.

4:30 p.m. EXECUTIVE SESSION (Members Only)

7:00 p.m. PRESIDENT'S RECEPTION (Tickets Required) Dominion Ballroom (2nd Floor)

*By Invitation