MONDAY AFTERNOON, MAY 8, 1989

1:30 p.m. SCIENTIFIC SESSION - HYNES BALLROOM

7. Clinical Experience With the Silicone Tracheal Prosthesis

WILLIAM E. NEVILLE, PAUL J.P. BOLANOWSKI*

AND GODSON KOTIA*

Newark, New Jersey

When extensive pathology precludes a primary anastomosis of the trachea an alternate method is mandatory to reconstitute a suitable airway. After several years of animal research we established to our satisfaction that a molded silicone tubular prosthesis was applicable in selected cases. In the past 17 years, 62 patients with benign and malignant tracheal stenosis have had airway reconstruction with this type of tube. A straight prosthesis was used in 48 patients. Twenty-nine had strictures, 2 TE fistula and stricture, 5 tracheal malacia and 14 malignancy. Either an end to end anastomosis of the graft to the resected tracheal margins was performed or the prosthesis was used as a permanent intraluminal stem. Eight individuals had non obstructive postoperative distal suture line granulomas, 2 had subglottic granulomas and one had dehiscence of the proximal anastomosis. Lazar excision was used to remove the granulomas and the dehiscence reattached. Eight patients died 1 to 3 years after surgery. In 14 patients with malignancy, 5 are alive 1-6 years, and 2 of 6 with an intraluminal stent, are living at 10 to 16 months. A palliative bifurcated intratracheal stent was used for palliation in 6 cases, 8 had a carinal resection - 4 are living 2-5 years.

Graft disruption, mediastinal infection, intraluminal prosthesis mucus encrustations and impedence of pulmonary secretions across long tubular segments had not occurred.

These silicone tubes are well tolerated and function satisfactorily as a permanent airway. From our observations these would seem to be a reasonable approach to the problem of complicated airway reconstruction.

*By Invitation

8. Airway Complications Following Double Lung Transplantation

G. ALEXANDER PATTERSON*, THOMAS R. TODD,

JOEL D. COOPER, F. GRIFFITH PEARSON,

TIMOTHY L. WINTON*

Toronto, Ontario, Canada and St. Louis, Missouri

En bloc Double Lung Transplantation (DLTX) is a therapeutic option to combined heart/lung transplantation in selected patients with bilateral end stage lung disease. While DLTX preserves the native heart, the donor airway, devoid of systemic arterial circulation is at risk of ischemia.

In the past 2 years, 14 DLTX have been performed in our centre. Seven recipients had emphysema and 3 patients had bronchiectasis. There was one patient with cystic fibrosis, 1 with bronchiolitis obliterans, 1 with pulmonary hypertension and 1 patient had eosinophilic granulomatosis. There have been 3 operative deaths and no late deaths. Major airway complications have occurred in 7 patients. Three patients developed fatal ischemic necrosis of the trachea and main bronchi. One patient underwent DLTX with bilateral main bronchial anastomoses, developed ischemic necrosis of the right bronchus and required retransplantation of the right lung. One patient developed partial donor tracheal necrosis which healed secondarily, leaving an anastomotic stricture. Two additional patients had satisfactory early airway healing, but developed late tracheal anastomotic and proximal left main broixchial strictures 2 months postoperatively. These latter 3 patients were treated by repeated bronchoscopic dilatations and transbronchoscopic placement of silastic bifurcation stents. These patients remain well up to 18 months with stents in place. Seven of 14 patients had excellent airway healing.

Patients with early airway necrosis had other postoperative complications (hemorrhage requiring re-exploration, 2 patients; rejection, 1 patient; bilateral pulmonary sepsis, 1 patient) which might decrease the pulmonary artery/bronchial artery collateral circulation to the donor airway. Notwithstanding the airway complications observed, 11 of 14 patients are alive and functioning normally following DLTX. By permitting separate extraction of heart and lung grafts for use in two recipients, DLTX has facilitated application of lung transplantation in our centre. We continue to employ this procedure in selected patients while seeking methods to achieve more reliable airway healing.

*By Invitation

9. Improved Survival Following Heart-Lung Transplant

PATRICK M. MCCARTHY*, VAUGHN A. STARNES*,

EDWARD B. STINSON, PHILIP E. OYER and

NORMAN E. SHUMWAY

Stanford, California

Fifty-five patients underwent heart-lung transplant (HLT) before 10/88. Thirty of these patients (operated on 3/81-2/86) were immunosuppressed using Cyclosporin A (CyA) and prednisone (P). These 30 patients (Group 1) are compared to the 25 most recent patients (Group 2) immunosuppressed using Cya, P, and Azathioprine (Aza). Patient characteristics (Group 1 vs. Group 2) were similar, including age (mean 32.4 years vs. 29.2 years) and indication for surgery (50% vs. 44% primary pulmonary hypertension, 47% vs. 48% Eisenmenger's complex, 3% vs. 8% other). Perioperative (in-hospital) mortality was 36.7% (11/30) in Group 1 vs. 8% (2/25) in Group 2 (p < 0.05). The linearized rejection rate (per 100 patient days) was similar in the first month after surgery (1.76 vs. 1.83). However, the linearized infection rate (per 100 patient days) in the first month was lower for the more recent patients (3.25 vs. 2.10, p< 0.001). Of the 19 hospital survivors in Group 1, 12 (63.1%) developed obliterative bronchiolitis (OB) from 44 to 1,461 days post-operatively (mean 361 days). Three (13.0%) of the 23 hospital survivors in Group 2 have developed OB, with a mean follow-up of 391 days (10-920) range). Overall, 23 of the 30 patients died in Group 1 (infection - 6, OB - 5, hemorrhage - 4). Four of the 25 patients in Group 2 died, all from infection. Survival for Group 1 patients was 60.0% one-year, 50.0% two-year, and 10.0% five-year versus 84.6% one-year and 84.6% two-year for Group 2 (p < 0.05).

A combination of improved immunosuppression with lower perioperative mortality has led to better early survival in our more recent HLT experience. Obliterative bronchiolitis has decreased in incidence and severity.

2:30 p.m. PRESIDENTIAL ADDRESS

W. Gerald Austen, Boston, Massachusetts

3:15 p.m. Intermission - Visit Exhibits

*By Invitation

3:45 p.m. SCIENTIFIC SESSION - HYNES BALLROOM

10. Evaluation of Heart-Lung Transplant Recipients with Prospective, Serial Transbronchial Biopsies and Pulmonary Function Studies

VAUGHN A. STARNES*, JAMES THEODORE*,

PHILIPE. OYER, MARGARETE. BILLINGHAM*,

RICHARD K. SIBLEY*, NORMAN E. SHUMWAY

and EDWARD B. STINSON

Stanford, California

The insidious development of obstructive airway disease (OB) following heart-lung (H-L) transplantation is thought to be secondary to rejection and possibly infection (CMV). To evaluate further, we studied prospectively the last 10 consecutive H-L transplants with serial transbronchial biopsies with lavage (TBXL) and pulmonary function studies (PFT's) as part of a surveillance protocol or as dictated by clinical presentation. Seventy TBSL's were performed, 40 for clinical indications (Group I) and 30 for surveillance (Group II). Twenty-nine (72.5%) of Group I biopsies were positive for rejection or infection. Five (16.7%) of Group II biopsies were positive for rejection or infection. Fifteen biopsies were positive for rejection (13 in Group I, 2 in Group II) characterized by perivascular mononuclear infiltrates, lym-phocytic bronchiolitis, and alveolar septal mononuclear infiltrates. Forty-four serial PFT's were performed. The forced vital capacity (FVC), FEF_25-75) and PaO₂ in Group I were significantly lower that Group II and correlated with positive biopsies: FVC - 51.4 ± 2.3 vs. 64.4 ± 3.6 (p= .003), FEF_25-75 -70 ± 6.3 vs. 98.2 ± 7.3 (p = .006), Pa0₂ - 74.7 ± 2.8 vs. 84.8 ± 2.l (p = .007).

The most significant fall in PFT's (FEF_25-75 , in particular) occurred in 6 patients with rejection and was reversed with treatment. Two patients developed OB with a history of continuing rejection and CMV pneumonitis.

Serial TBXL, as dictated by PFT's and clinical status, has guided early and more specific therapy directed against rejection and infection. With early detection, airway disease has been reversible.

*By Invitation

11. Multiple Primary Lung Cancers: Results of Surgical Management

CLAUDE DESCHAMPS*, PETER C. PAIROLERO,

VICTOR F. TRASTEK* and W. SPENCER PAYNE

Rochester, Minnesota

From July 1970 to October 1983, 117 consecutive patients were diagnosed as having multiple primary cancers of the lung. Eighty patients (63 men, 17 women) underwent curative pulmonary resection (PR) for at least 2 cancers. Forty-four of these 80 patients (age 39-81 years; median, 61 years) presented with metachronous cancers. The interval between diagnoses ranged from 4 to 90 months (median, 24 months). The initial PR was wedge or segmentectomy in 4 patients, lobectomy in 36, bilobectomy in 3, and pneumonectomy in 1. The cancer was post-surgical stage I in 41 patients and stage II in 3. There were no operative deaths. The second PR was wedge or segmentectomy in 19 patients, lobectory in 16, bilobectomy in 2, and completion pneumonectomy in 7. There were two 30-day operative deaths (mortality, 4.5%). Eleven patients developed a third cancer; 6 of whom had a third PR. Actuarial 5 and 10 year survival following the first PR was 55.2% and 27% respectively. Five year survival following the second PR was 33.8%.

The remaining 36 patients, (age 40-84; median, 67.5 years) presented with synchronous cancers. Three patients underwent staged bilateral PR. The PR was wedge or segmentectomy in 8, lobectomy in 18, bilobectomy in 3, and pneumonectomy in 10. The cancer was postsurgical stage I in 24 patients, stage II in 7, stage IIIA in 4, and not staged in 1. There were two 30-day operative deaths (mortality 5.5%). Six patients later developed a third lung cancer, and all underwent another PR. Actuarial 5 year survival after PR was 15.7% which was significantly less than the survival observed after resection of the second cancer in the metachronous group (P<.05).

We conclude that an aggressive surgical approach is safe and warranted in most patients with multiple primary lung cancers and that the finding of synchronous primary cancers is an ominous event.

*By Invitation

12. Primary Mediastinal Nonseminomatous Germ Cell Tumors: Results of a Multimodality Approach

CAMERON D. WRIGHT*, KENNETH A. KESLER*,

CRAIG R. NICHOLS*, YOUSUF MAHOMED*,

LAWRENCE H. EINHORN*, MICHAEL E. MILLER*

and JOHN W. BROWN

Indianapolis, Indiana

Prior to cisplatin-based chemotherapy (CTX), long-term survival following resection of primary mediastinal nonseminomatous germ cell tumors (PMGCT) was unusual. We reviewed 48 patients with PMGCT who underwent an integrated treatment program including CTX, serial serum tumor marker (STM) assays, and surgery. All patients were males ranging from 14 to 46 years of age. Forty-four patients (92%) had either one or both STM elevated at the time of diagnosis. Five patients had choriocarcinoma, 4 embryonal carcinoma, 11 yolk sac carcinoma, 4 teratocarcinoma, 22 mixed cell type, and 2 had an unclassified PMGCT. Twenty-six patients had a complete response to treatment as defined by both normalization of STM and absence of residual tumor. In this group, 20 patients obtained a complete response by CTX and subsequent surgical resection, 4 with either total or near total resection followed by CTX, and 2 with CTX alone. Incomplete responders included 17 patients who failed to normalize STM after CTX, 2 with incomplete resections, and 3 with progressive disease during CTX. There was no operative mortality or significant morbidity. Overall actuarial survival was 32% at 5 years with a mean follow-up of 50 months. Five year actuarial survival was 64% if a complete response was obtained in contrast to 0% (p<.0001) if not. An 89% 5 year survival was achieved in 13 complete response patients with only mature teratoma found in the surgical specimen. Other favorable prognostic factors include presence of teratoma elements before CTX (p<.001), absence of persistent PMGCT or non-germ cell tumor after CTX (p<.002), absence of pulmonary metastasis at diagnosis (p<.002), and normalization of STM after CTX (p<.001). A multimodality approach to PMGCT including aggressive surgical resection and cisplatin-based chemotherapy now offers survival to a significant number of patients.

*By Invitation

13. Chemo-Radiation Therapy and Resection for Carcinoma of the Esophagus: Long-Term Results

EDWARD F. PARKER, CAROLYN E. REED*,

RICHARD D. MARKS*, JOHN M. KRATZ* and

MARY CONNOLLY*

Charleston, South Carolina

From May, 1980 - 1984, preoperative chemotherapy (Mitomycin C and 5-FU) was added to radiation therapy in potentially operable patients with squamous cell carcinoma of the esophagus. Of 129 patients observed, only 33 were able to complete preoperative chemotherapy and radiation and undergo resection. There were 28 men and 5 women, ranging in ages from 42 to 81 yrs. (ave 60). Twenty-two patients were Black and 11 White. The location of the tomor was in the middle third in 70% of the cases. Clinical TNM classification was as follows: 3 cases TiN₀Mo, 27 cases T₂N₀M₀, 2 casesTiN.Mo, 1 case T₃N₀M₀. The length of the lesions, where measurable in the absence of complete obstruction, varied from 3 to 17 cms (ave 7 cms). Operative mortality in this group was 12% (4/33). There was no residual tumor in the surgical specimen of the esophagus in 33% (11/33) of those patients completing triple therapy. However, in two of these patients celiac nodes contained tumor and in one there was a minute esophageal perforation. The two-year survival rate was 33% (11/33), and the 5-year survival rate 15.4% (5/33). Of the 11 cases having 2-year survival, the surgical specimen was negative in 6 and positive in 5. Of the 5 cases having 5-year survival, the surgical specimen was negative in 3 and positive in 2. The absence of tumor in the surgical specimen did not appear to confer any better chance for long-term survival. Data was compared to our 1967-75 series of 75 patients receiving only preoperative radiation and resection. There was no significant difference in survival at two years [20% (1975) vs 33% (1984), p = .2118] or at five years [10% (1975) vs 15.4% (1984), p = .5796]. The addition of preoperative chemotherapy as an adjunct did not result in a statistically significant increase in 2-year or 5-year survival.

5:05 p.m. ADJOURN

*By Invitation