WEDNESDAY MORNING, APRIL 28, 1993

7:30 a.m. FORUM SESSION II - Grand Ballroom

GENERAL THORACIC SURGERY

Moderators: Douglas J. Mathisen, M.D.

Martin F. McKneally, M.D.

F10. Cold Ischemia and Reperfusion Each Produce Pulmonary Vasomotor Dysfunction in the Transplanted Lung

DAVID A. FULLERTON, M.D.*, MAX B. MITCHELL, M.D.*,

ROBERT C. McINTYRE, M.D.*,

ANIBAN BANERJEE, Ph.D.*, DA VID N. CAMPBELL, M.D.*,

ALDEN H. HARKEN, M.D. and

FREDERICK L. GROVER, M.D.

Denver, Colorado

BACKGROUND Pulmonary vascular resistance (PVR) is significantly increased in the transplanted lung. Ischemia and/or reperfusion incurred by the transplanted lung may produce pulmonary vasomotor dysfunction, which may in turn contribute to increased PVR. Therefore, the following pulmonary vasomotor control mechanisms were studied in a canine model of autologous lung transplantation and each related to Cold Ischemia and Reperfusion: (1) Endothelial-dependent cGMP-mediated dilation (response to Acetylcholine, ACh) (2) Endothelial-independent cGMP-mediated dilation (response to Nitroprusside, NP) and (3) Vascular smooth muscle Beta adrenergic cAMP-mediated dilation (response to Isoproterenol, ISO).

METHODS Autologous lung transplantation was performed in 5 dogs. After infusing PGE₁ (10µ/kg), modified Euro-Collins Solution (4°C, 30cc/kg) was infused into the right pulmonary artery. The right lung was removed, stored in saline (4°C) for 3 hrs, then reimplanted. 2 third order pulmonary arteries were dissected from each lung at each of 3 times: Control (immediately post harvest), Cold Ischemia (3 hrs in saline 4°C), Cold Ischemia plus Reperfusion (1 hr after lung reimplantation). The vasorelaxing effects of ACh 10^-6M, NP 10^-6M, and ISO 10^-6M were studied in isolated pulmonary arterial rings, suspended on fine wire tensiometers in individual organ chambers. Statistical analysis was by ANOVA (Scheffe's F-test).

RESULTS Reperfusion produced endothelial dysfunction as the response to ACh, but not NP, was impaired. However, vascular smooth muscle Beta adrenergic relaxation (response to ISO) was impaired by cold ischemia alone, and worsened by reperfusion.

CONCLUSION Cold ischemia and reperfusion each produce different patterns of pulmonary vasomotor dysfunction. Cumulatively, such dysfunction may contribute to increased PVR in the transplanted lung.

*By Invitation

F11 Successful Canine Bilateral Single Lung Transplantation After 21-Hour Lung Preservation

HIROSHI DA TE, M.D.*, SADANOBU IZUMI, M.D.*,

YOSHIO MIYADE, M.D.*, AKIO ANDO, M.D.*,

NOBUYOSHISHIMIZU, M.D.* and

SHIGERU TERAMOTO, M.D.*,

Okayama, Japan

Sponsored by: Joel D. Cooper, M.D., St. Louis, Missouri

We utilized a bilateral single lung transplantation (BSLT) model to confirm the results of lung preservation studies previously obtained in a canine single lung transplant model. The donor lungs were flushed with low potassium dextran glucose (LPDG) solution, inflated with 100% oxygen and preserved at 8°C. After the preservation period, BSLT was performed without using a cardiopulmonary bypass. In group I (n = 5), the mean ischemic time of the right lung was 3 hrs 5 min ± 27 min and for the left lung 6 hrs 2 min ± 33 min. In group II (n = 5), they were 18 hrs 8 min ± 27 min and 21 hrs 42 min ± 42 min, respectively. Following BSLT, animals were maintained on a ventilator for 12 hours and pulmonary function was monitored. All five cases in group I and four of five cases in group II completed BSLT and survived for 12 hours with excellent lung function as shown below:

PaO2	1hr	2hrs	4hrs	6hrs	8hrs	10hrs	12hrs
Group I	538 ± 44	563 ± 49	559 ± 15	534 ± 14	528 ±36	569 ±22	590 ±18 mmHg
Group II	565 ± 67	534 ± 96	510 ± 99	498 ± 99	507 ± 99	623 ± 19	615 ±18 mmHg
mPAP
Group I	27 ± 4	27 ± 3	27 ±3	27 ±4	27 ±3	27 ± 3	27 ± 3 mmHg
Group II	23 ± 3	23 ± 2	24 ± 3	22 ± 3	22 ± 3	20 ± 4	20 ± 4 mmHg
(FiO, = 1.0, mPAP: mean pulmonary artery pressure)

Following the 12 hour period of post-transplant assessment, the animals were extubated. All animals in each group showed satisfactory spontaneous ventilation and were returned to the cage. FK506 (0.1 mg/kg) was given intramuscularly every day. Despite the excellent immediate graft function, survival of the animal was modest. The longest survival time was 4 days in group I and 8 days in group II. In no case did postmortem examination of the lungs reveal any overt signs of lung injury. The animal in group II which died of bronchial dehiscence at 8 days snowed excellent arterial blood gas on room air for 6 days as shown below:

	1 day	3 day	6 day
PaO2	79.3	75.0	70.5 mmHg
PaCO2	36.1	37.9	36.8 mmHg

We conclude that lungs flushed with LPDG solution, inflated with 100% oxygen and preserved at 8°C for 21 hours provides excellent immediate and very satisfactory early graft function in a canine BSLT model in which the animal is totally dependent on the function of transplanted lung tissue.

*By Invitation

F12. Detection of Canine Allograft Lung Rejection by Pulmonary Lymphoscintigraphy

RENATO RUGGIERO, M.D.*, ROBERT FIETSAM, M.D.*,

GREGORY A. THOMAS, M.D.*,

JAROSLAW MUZ, M.D.*, THOMAS A. KOWAL, P.A.*,

JONA THAN L. MYLES, M.D.*,

LARRY W. STEPHENSON, M.D. AND

FRANK A BACIEWICZ, M.D.*

Detroit, Michigan

We previously demonstrated that lymphoscintigraphy could be used to study pulmonary lymphatic flow. Radiocolloids, high molecular weight protein tagged with radioactive markers, are injected percutaneously in the periphery of the lung, these molecules enter the lymph, are transported via lymphatic channels and concentrated in the tributary hilar and mediastinal lymph nodes where they can be detected by nuclear scan.

The goal of this study was to determine whether pulmonary lymphoscintigraphy could be used to detect allograft rejection after lung transplantation.

Thirteen mongrel dogs underwent left lung allotransplantation using standard surgical techniques. Cyclosporine 15 mg/kg/day and azathioprine 1 mg/kg/day were given orally for postoperative immunosuppression. Lymphoscintigraphic studies were obtained one week after the surgery and then at weekly intervals. Animals were divided into groups A and B. In group A (n = 5), immunosuppression was continued until the animals death (n = 1) or until they were euthanized at six weeks. Lymphoscintigraphy demonstrated re-establishment of lymphatic drainage between the lung graft and the mediastinum in all (n = 5) the animals two to four weeks after the transplant. In Group B (n = 8), immunosuppressive medications were discontinued after re-establishment of graft lymphatic drainage was documented by two consecutive lymphoscintigraphic studies. The dogs continued to be studied with weekly scans. In this group, lymphatic drainage from the lung graft to the mediastinum disappeared between one and three weeks following discontinuation of the immunosuppressive medications. Rejection was diagnosed clinically and confirmed histologically with open lung biopsies in group B. The difference in disappearance of lymphatic drainage between groups A and B was statistically significant (p<0.001).

This study shows that canine allograft lung rejection is associated with disappearance of lymphatic drainage from the lung graft to the mediastinum. The significance of this finding is not yet clear but was documented by pulmonary lymphoscintigraphy, a minimally invasive technique that can be easily repeated. Pulmonary lymphoscintigraphy may be useful for early clinical detection of lung allograft rejection.

*By Invitation

F13. Isolated Single Lung Perfusion With Doxorubicin is Effective in the Treatment of Metastatic Sarcoma in the Rat

BENNY WEKSLER, M.D.*, BRUCE NG, B.S.*,

JEFFREY T. LENERT, M.D.* and

MICHAEL E. BURT, M.D., Ph.D.

New York, New York

Currently the only effective therapy for patients with soft-tissue sarcoma metastatic to the lung is resection, with five year survival after resection approximating 25%. Systemic chemotherapy has not impacted on survival. We have previously shown that isolated single lung perfusion (ILP) with dox-orubicin (DOX), in the rat, results in significantly higher tissue concentration than systemic injection. We evaluated the efficacy and toxicity of ILP with DOX and the treatment of rat sarcoma lung metastases.

Methods: Experiment 1. Three groups of F344 (n = 5) rats were randomized to left ILP for 10 min. at 0.5 ml/min, with perfusate concentrations of 320, 480 or 640 ug/ml of DOX in saline. Right pneumonectomy was performed 21 days post-perfusion. Experiment 2. Twenty F344 rats had intravenous injection of 10⁷ methylcholanthrene-induced sarcoma cells. Six days post-injection, 10 animals were randomized to ILP with 320 ug/ml of DOX and 10 animals to ILP with saline. On day 20 all animals were sacrificed and lungs were examined for number of metastases. Statistical analysis by Fisher exact test. Significance defined as p<0.05.

Results: Experiment 1. Survival after left ILP followed by right pneumonectomy was 80%, 0%, 0% with 320, 480, 640 ug/ml of DOX, respectively (p<0.05). Experiment 2. Three animals died post-operatively, 2 from the saline group and one from the DOX group; one animal from the DOX group was excluded due to the presence of mediastinal tumor noticed during ILP. Seven out of 8 animals perfused with DOX had total clearing of the left lung and all animals perfused with saline had the left lung fully replaced with tumor (p<0.001). All right unperfused lungs were completely replaced.

Conclusion: Isolated single left lung perfusion with 320 ug/ml of DOX does not cause morbid lung injury since 80% of animals perfused survived contralateral pneumonectomy. ILP with DOX is effective in eradicating metastatic sarcoma in this model.

*By Invitation

F14. Tumor Necrosis Factor Induces Doxorubicin Resistance in Lung Cancer

THOMAS W. PREWITT, M.D.*,

WILBERT MATTHEWS, B.S.*, GEETA CHAUDHRI, Ph.D.*,

HELEN W. POGREBNIAK, M.D.*

and HARVEY I. PASS, M.D.

Bethesda, Maryland

Cytokines can alter the cell cycle (CC) of tumor cells and aid hemopoetic stem cell recovery from chemotherapy. We theorized that cytokines might alter the chemosensitivity of cancer cells by CC modulation. METHODS: A549 human lung cancer cells were exposed for 24 hours to TNF, IL-1, or IL-6. CC kinetics were then measured by flow cytometry (n = 4). Six day growth of TNF exposed A549 was measured via the MTT assay (n = 3). A549 cells were treated for 24 hours with 1 µg/ml TNF or control media (CM), then exposed to 1 hour of DOX (n = 4), cis-platinum (CDDP, n = 3), or mitomycin C (MITO, n = 3), and 8 day survival fractions measured by clonal assay. Intracellular DOX levels were determined by fluorescence spec-trophotometry to rule out any effects on [DOX] by TNF preexposure.

RESULTS: TnF shifted A549 from S phase to (G₀/G,) as seen below:

CELL CYCLE EFFECTS OF TNF ON A549 CELLS
TNF mg/ml	0	0.001	0.01	1.0
% cells in G0G1	53 ± 1	54 ± 3	62 ± 4*	65 ± 1*
% cells in S phase	40 ± 3	42 ± 5	34 ± 3	31 ± 1*

*p_;<0.05 from 0 /mg/ml TNF

This shift to the resting phase of the CC was verified by inhibition of A549 growth in TNF over 6 days (1.9 ±.2OD vs 1.4 ± .1 OD, 0 vs 1 µg/ml TNF, p₂<.05). TNF pre-treatment rendered A549 resistant to DOX, a CC- specific drug, as seen below.

SURVIVAL OF DOX-EXPOSED A549 ± TNF PRETREATMENT
[DOX]	0.50	1.00	2.50	5.0	10.0
mM
-TNF	0.80 ± .13	0.53 ± .09	0.09 ± .04	0.033 ± .02	0.011 ±.004
+TNF	0.90 ± .11	0.57 ±.09	0.34 ± .08*	0.170 ± .04*	0.034 ± .007*

*p_;<0.05, CM vs TNF

TNF did not affect intracellular DOX levels. Moreover, TNF did not affect chemosensitivity to CDDP or MITO, which are not CC-specific.

CONCLUSIONS: (1) TNF induces chemoresistance in lung cancer cells. (2) This chemoresistance may involve shift of cells into the CC resting phase. (3) Local elaboration of TNF by tumor associated macrophages may induce chemoresistance and could in part explain treatment failure in lung cancer.

*By Invitation

F15. A High Frequency of p53 Mutations Occurs in Patients With Squamous Cell Carcinoma of the Esophagus

CHRISTOPHER E. GA TES, M.D.*,

CAROL YN E. REED, M.D.*, JONA THAN S.

BROMBERG, M.D., Ph.D.*, ERIC T. EVERETT, M.S.*,

ROBERTA L.D. DIKEMAN, B.S.* and

PAUL L. BARON, M.D.*

Charleston, South Carolina

Sponsored by: Fred A. Crawford, Jr., M.D., Charleston,

South Carolina

Coastal South Carolina has one of the highest rates of esophageal cancer in the world. Although environmental exposures have been implicated in its development, their precise role in generating and promoting tumorogenesis has not been established. Mutations in the p53 tumor suppressor gene have been described in 35% of esophageal cancers from other high incidence areas, namely, China and Southern France. Our study was designed to determine if patients with squamous cell carcinoma of the esophagus from the South Carolina Lowcountry have p53 mutations and whether the pattern of such mutations correlates with their environmental exposures. Specimens obtained by esophagoscopy were either grown in tissue culture or cryopreserved in liquid nitrogen. The total cellular RNA was extracted and reverse transcribed to cDNA. A 606 base pair segment of the expressed p53 gene spanning exons four through nine (the region with 98% of the known mutations) was selectively amplified by the polymerase chain reaction, cloned into pBluescript II KS + plasmids, grown in competent E. coli, and sequenced by a modification of the dideoxy random chain termination method. All eight patients has a significant history of heavy tobacco use:

Overall five of eight squamous cell tumors had at least one missence mutation (63%) with all five being found in freshly frozen specimens. (Cases RA and HL were prepared from cultured samples.) Mutation at a CpG di-nucleotide or a transition from G to A occurred at four of the six different mutations. These are the expected sites for mutations caused by deaminating and alkylating agents. Such mutagens are present in significant quantities in tobacco. In conclusion, squamous cell carcinomas of the esophagus in patients from the South Carolina Lowcountry have a high frequency of p53 mutations, and it may be speculated that the mutational spectrum is consistent with their common exposure to tobacco use.

*By Invitation

F16. Molecular Markers of Poor Prognosis in Adenocarcinoma of the Lung Define Unique Groups of Patients

RICHARD I. WHYTE, M.D.*, PHILIP F. BONGIORNO, M.D.*,

ERIC J. LESSER*, JASON H. MOORE, B.S.*,

MARK B. ORRINGER, M.D. and

DAVID G. BEER, Ph.D.*

Ann Arbor, Michigan

The development of human adenocarcinoma of the lung involves multiple genetic changes including activation of oncogenes and loss of tumor suppressor genes. Patients whose lung tumors contain either mutation or nuclear protein accumulation of the tumor suppressor gene p53, K-ras oncogene mutation of erbB-2/neu protein overexpression have been shown to have a worse prognosis. We examined these three genetic indicators in 29 lung adenocarcinomas to determine if these markers are present in the same tumors or if they represent molecular changes which define different subsets of patients. P53 nuclear protein accumulation and erbB-2/neu protein overexpression were determined using immunohistochemical analysis of cryostat sections of tumor specimens and the corresponding normal lung tissue. ErbB-2/neu gene amplification was examined by Southern blot analysis. K-ras mutations were detected by radiolabeled oligo probes, specific for the various 12th codon mutations, hybridized to tumor DNA amplified by polymerase chain reaction. Increased nuclear accumulation of p53 protein was found in 10 adenocarcinomas (34%). All of the p53 positive tumors were found to show high level staining and homogenous expression of erbB-2/neu protein. K-ras mutations were detected in 6 tumors (21%), all of which overexpressed erbB-2/neu. The presence of a K-ras mutation did not correlate with p53 expression. In total, 86% of the tumors were found to over-express erbB-2/neu with the highest in tumors with erbB2/neu gene amplification. In conclusion, erbB-2/neu overexpression is a common event in lung adenocarcinomas. Furthermore, the presence of K-ras mutation and p53 protein accumulation define separate groups of patients. The mechanisms by which these genetic alterations adversely affect prognosis or interact are unknown.

*By Invitation

F17. Carcinogenic Specificity of P53 Tumor Suppressor Gene Mutations in Lung Cancer

DANIELA KANDIOLER, M.D.*,

MANUELA FODINGER, M.D.*,

MICHAEL ROLF MULLER, M.D.*,

PROF. CHRISTINE MANNHALTER*,

PROF. FRANZ ECKERSBERGER*

and PROF. ERNST WOLNER

Vienna, Austria

Mutations in the p53 tumor suppressor gene, whose encoded protein is one of the chief regulators of the cell cycle, are proving to be the most common genetic alteration in human cancers. Point mutations have been detected in numerous types of human solid tumors. Interestingly, the mutations are clustered in four regions of the gene which coincide with regions highly conserved through evolution. However, in lung cancer there is reason to believe that an additional hot spot region for mutations exists.

To investigate the role of p53 mutations in the development of lung cancer we have so far examined tumor specimens from 28 patients with different types of lung cancer (13 squamous cell, 6 large cell and 9 adenoid carcinomas). We extracted total RNA from tumor specimens and from corresponding normal material and peripheral blood as a control from each patient. Total RNA was reverse transcribed into cDNA, and cDNA sequences corresponding to the 11 exons of the p53 gene were amplified using polymerase chain reaction (PCR). Using single strand conformation polymorphism analysis we could detect the exact exon which contained the mutation and subsequently sequenced this exon.

17/28 patients showed p53 point mutations in tumor tissue. No mutations could be found in the corresponding normal tissue or peripheral blood, indicating that the mutations we found are somatic, acquired events. 50% of mutations were located in the additional hot spot region mentioned above. This region is not affected by mutations in other tumors. In 9 of 17 point mutations, the nucleotide guanidine was replaced by thymidine (G-T transversion). This mutation has occasionally been described for hepatocar-cinomas but never for colon carcinomas although the overall incidence for p53 mutations is about the same.

Lung cancer is one of the most common cancers characterized by a well defined risk factor as there is exposure to carcinogen. Environmental car-cinogenes like benzpyrene have been shown to cause G-T transversions in vitro. In our patients we found that age and a history of smoking were associated with the occurrence of G-T transversions. Our results indicate that the nature and position of p53 mutations are influenced by tissue type which may be due to differences in exposure to mutagens of these cells.

*By Invitation

F18. Pain Management for Thoracotomy: Thoracic Epidural Versus Paravertebral Block

GILBERT J. GRANT, M.D.*, KRISTIEN VERMEULEN, M.D.*,

HERMAN TURNDORF, M.D.*

and ARTHUR D. BO YD, M.D.

New York, New York

Background/Objective: After thoracotomy, patients experience intense pain and a significant decrease in pulmonary function. Continuous thoracic epidural (EPI) analgesia has been considered the optimal method for post thoracotomy pain control, but recently continuous extrapleural paravertebral (PARA) nerve block for post thoracotomy analgesia has been described. This study was designed to compare the effectiveness of these two methods for post thoracotomy analgesia.

Methods: Twenty-five patients undergoing pulmonary resection were randomized to 2 groups (EPI = 12, PARA= 13). EPI catheters were inserted at T5-6 or T6-7 levels before surgery. PARA catheters were placed during surgery into a paravertebral parietal pleural pocket extending two in-sterspaces above and below the incised interspace. Prior to rib approximation, the EPI group received a 0.2 mg/kg bolus of 0.125% bupivacaine + fentanyl 2 µg/ml; the PARA group received a 0.3 ml/kg bolus of 0.25% bupivacaine. An infusion of bupivacaine 0.125% + fentanyl 2 µg/ml was then started in both groups at 0.1 ml/kg/hr. Pain was managed by giving a 0.15 ml/kg bolus and increasing the infusion in 0.01 ml/kg/hr increments as needed. Pain scores and blood gases were obtained. FEV,, VC, and FVC were assessed preoperatively and at 6 and 24 hours postoperatively.

Results: Age, weight, sex and surgery were similar in both groups. PARA patients required more bupivacaine (342 ± 56 mg) and fentanyl (632 ± 90 µg) during the first postoperative day than EPI patients (bupiv 237 ±61; fent 379 ±98 µg). Pain was well controlled in both groups, with no significant differences in pain scores or blood gases. Arterial pressure was lower in EPI than PARA patients between 14-16 hours postoperatively. FEV,, VC, and FVC were all significantly lower than preoperative values, but there were no intergroup differences (expressed below as % pre-op):

FEV1 6h	FEV1, 24h	VC 6h	VC 24h	FVC 6h	FVC 24h
PARA	60 ± 19	60 ± 16	52 ± 13	56 ± 17	56 ± 15	55 ± 13
EPI	57 ± 17	57 ± 18	50 ± 14	53 ± 15	56 ± 15	53 ± 17

Conclusions: Continuous PARA block is as effective as continuous EPI block. Thus, PARA block should be considered as an excellent alternative to EPI block for post thoracotomy pain relief.

*By Invitation

WEDNESDAY MORNING, April 28, 1993

9:00 a.m. SIMULTANEOUS SCIENTIFIC SESSION D CARDIAC SURGERY

Grand Ballroom B

Moderators: Delos M. Cosgrove, M.D.

Robert A. Guyton, M.D.

38. Long Term Results of Mitral Valve Reconstruction for Regurgitation of the Myxomatous ("Floppy") Mitral Valve

LAWRENCE H. COHN, M.D., GREGORY S. COUPER, M.D.*,

ROBERT J. RIZZO, M.D.*, SARYF. ARANKI, M.D.*,

NANCY M. KINCHLA, B.S.*

and JOHN J. COLLINS, JR., M.D.

Boston, Massachusetts

The myxomatous, prolapsed or "floppy" mitral valve is the most common etiology of mitral regurgitation (MR) in North America. Mitral valve reconstruction for MR was carried out on 201 consecutive patients with a myxomatous mitral valve, from 1984 - 1992. There were 127M/74F, aged 23-84 years, 63 years; 35% of patients ≥70 years, 78% were in Functional Class III or IV, and 30% had coronary artery disease requiring coronary bypass.

The posterior leaflet was resected in 146 patients (73%), the anterior leaflet in 14, anterior and posterior leaflet in 12, chordoplasty plus annuloplasty ring in 10 patients, and a commissuroplasty plus annuloplasty ring in 19 patients. A flexible Duran ring was used in 95 patients (47%), Carpentier ring in 45 patients (22%), and no ring was used in 61 patients (30%). There were 5 operative deaths (2.5%); 4/5 occurred in patients ≥70 (5.7%); only 1 death occurred in the 131 patients <70 years of age (0.8%).

In the late postoperative period (mean follow-up 3 years), 90% of patients are asymptomatic, 2 developed endocarditis (IVD), 6 patients had throm-boemboli, (4 transient, 2 permanent). Structural valve degeneration (SVD) requiring reoperation occurred late in 12 patients; 8 were in posterior leaflet resection, 2 in anterior or anterior and posterior; 6/12 had no annuloplasty ring. There was a zero incidence of systolic anterior motion of the mitral valve noted on postoperative echo prior to discharge. Actuarial analysis at 5 years is indicated below:

	5 Years
Overall Survival	86 ± 5 %
Freedom from IVD	98 ± 2%
Freedom from TE	93 ± 2%
Freedom from SVD
Overall	83 ± 4%
Flexible Ring	91 ± 5%
Rigid Ring	85 ± 6%	p = .05
No Ring	68 ± 12%
Freedom from Reoperation	84 ± 4%

Mitral valve reconstruction for complicated myxomatous disease of the mitral valve, regardless of leaflet involvement, is feasible and offers excellent early and late results.

*By Invitation

39. The Use of Homograft Valves for Reoperations on the Aortic Valve

MARIO ALBERTUCCI, M.D.*, KIT WONG, FRCS*,

STERGIOS THEODOROPOULOS, M.D.*

MARIO PETROV, M.D.* and MAGDI YACOUB, FRCS

London, England

Homograft Valves offer several theoretical advantages when used for patients who have had previous operations on the Aortic Valve. Between 1972 and 1992, 110 patients received Aortic Homografts after previous Aortic Valve operation, 84 patients had previous Aortic Valve Replacement (Homograft in 69, Prosthetic Valves in 11 and Stented Xenografts in 4) while 26 had previous Valve Repair. The indication for reoperation was Valvular Deterioration or Malfunction in 82 (75%) and Endocarditis in 28 patients. The valves were obtained under sterile conditions in 20 and sterilized in Antibiotics in 90.

The Homograft was used to replace the Aortic Valve and root in 32 patients and inserted in the subcoronary position in the remaining 78 patients. The hospital mortality was 5% and was not influenced by the type or number of previous operations or the presence or absence of Aortic Endocarditis (P>0.1). Homografts were particularly useful in patients with active Endocarditis on the native or Prosthetic Valve who had multiple root abcesses. None of the patients developed recurrence of infection within the first 6 months after the operation. The acturarial survival free of Valve related complications was 78% at 10 years.

It is concluded that reoperations using Unstented Aortic Homografts give good early and medium term results and offer considerable advantages for patients with Endocarditis on previously replaced Valves.

*By Invitation

40. Reoperation After Mitral Valve Reconstruction: Analysis of 33 Cases

EUGENE A. GROSSI, M.D.*, AUBREY C. GALLOWAY, M.D.*,

JULIE DELIANIDES, M.A.*, GREG H. RIBAKOVE, M.D.*,

MARTIN LeBOUTILLIER, M.D.*,

F. GREGORY BAUMANN, Ph.D.*,

FRANK C. SPENCER, M.D. and

STEPHEN B. COLVIN, M.D.*

New York, New York

From 1/80 through 6/92, 664 patients (pts) underwent mitral valve repair using Carpentier reconstructive techniques. Of those pts, 33 (5.0%) have subsequently required reoperations from one day to 8.3 yrs postoperatively (mean interval = 2.3 yrs; mean age = 46 yrs, range 13-82 yrs). The etiology of the original mitral disease was rheumatic in 11 pts (33%), degenerative in 8 pts (24%), ischemic in 7 pts (21%), congenital in 6 pts (18%) and endocarditis in 1 pt (3%). Reoperative mortality was 6.1%.

Early reoperation (<6 months, n = 10) was attributed to technical problems in 5 pts (50%) (ring dehiscence in 3 pts, non-quadrangular leaflet resection in 1 pt, and inappropriate repair of a congenital valve in 1 pt), endocarditis in 2 pts (20%), ischemia with ruptured chordae in 2 pts (20%), and rheumatic disease in 1 pt (10%). Technical or judgement errors accounted for 6 of 10 (60%) early failures. Re-repair was accomplished successfully in 2 pts (20%).

Late operation (>6 months, n = 23) was due to rheumatic disease in 9 pts (39%), progression of non-rheumatic disease (chordal rupture and leaflet retraction) in 5 pts (22%), endocarditis in 6 pts (26%) and technical problems (ring dehiscence or ring malorientation) in 3 pts (13%).

Potentially preventable errors in judgment and technique are responsible for 60% of the early and 13% of the late failures after mitral valve reconstruction. Rheumatic disease remains the primary cause of late reoperation.

*By Invitation

41. Determinants of Reoperation After 963 Valve Replacements With Carpentier-Edwards Prostheses

DONALD D. GLOWER, M.D.*, WILLIAM D. WHITE, M.P.H.*,

ANGELA C. HATTON, B.A.*,

W. GLENN YOUNG, M.D., WALTER G. WOLFE, M.D.

and JAMES E. LOWE, M.D.

Durham, North Carolina

During the period of 1977-1990, 963 Carpentier-Edwards Standard valve prostheses were placed in 879 operations (368 aortic, 374 mitral, 59 tricuspid, 1 pulmonic, 58 aortic and mitral, 1 aortic and tricuspid, 11 mitral and tricuspid, 7 aortic and mitral and tricuspid). Over 4795 patient-years of follow-up, 206 Carpentier-Edwards valves required reoperation with freedom from reoperation at 8/10/12 years being 72 ± 3/54 ± 4/39 ± 5% for mitral valve replacement and 85 ± 3/71 ± 4/61 ± 5% for aortic valve replacement. By Cox univariate proportional hazards model, preoperative comor-bidity, gender, ejection fraction <40%, left main or 3 vessel coronary disease, concurrent coronary bypass, and concurrent valve operation did not affect the likelihood of reoperation. The only independent determinant of reoperation for aortic and mitral valves was age. Likelihood of reoperation decreased with age (p<0.05) with freedom from reoperation after 10 years in patients aged <60 yrs vs ≥60 yr being 60 ± 5 vs 84 ± 5% after aortic valve replacement and 45 ± 5 vs 72 ± 6% after mitral valve replacement. For mitral valve replacement, larger valve size made reoperation more likely (p = 0.01, 80/101 for prosthetic dysfunction) with freedom from reoperation at 10 years being 63 ± 6% for sizes <31 mm and 47 ± 6% for sizes ≥31 mm. For aortic valve replacement, any prior valve procedure increased the likelihood of reoperation (p<0.01), with freedom from reoperation at 10 years falling from 75 ±4% to 32 ± 12% when any prior valve procedure was present.

Thus, the low incidence of reoperation affirms the suitability of the Carpentier-Edwards prosthesis for selected patients over the age of 60 years. Reoperation is more likely for large mitral sizes primarily due to prosthetic dysfunction and for aortic valve replacement after a prior valve procedure. Comorbidity and concurrent valvular operation have relatively little effect on the likelihood of reoperation and should have less influence on the choice of valvular prosthesis.

10:20 a.m. INTERMISSION - VISIT EXHIBITS

*By Invitation

11:05 a.m. SIMULTANEOUS SCIENTIFIC SESSION D CARDIAC SURGERY

Grand Ballroom B

42. Early and Late Phase Events Following Valve Replacement With the St. Jude Medical Prosthesis in 1,200 Patients

JAVIER FERNANDEZ, M.D., GLENN W. LAUD, M.D.*,

MARK S. ADK1NS, M.D.*, WILLIAM A. ANDERSON, M.D.*

and CHAO CHEN, Ph.D*, BRIDGET M. BAILEY, B.S.N.*,

LINDA M. NEALON, B.S.N.* and

LYNN B. MCGRATH, M.D.

Browns Mills, New Jersey

The object of this investigation was to determine early and late phase events following valve replacement with the St. Jude Medical (SJM) valve. From May, 1982 to August, 1991, 1200 patients (pts) underwent valve replacement with the SJM valve. There were 615 males (51%) and 585 females. Ages ranged from 2 to 89 yrs, mean 58 yrs. Preoperatively, 830 pts (69%) were in functional class III and IV. Six-hundred eleven pts (51%) had aortic valve replacement (AYR), 490 (41%) had mitral valve replacement (MVR), 2 (0.2%) had tricuspid valve replacement (TVR), and 97 (8%) had multiple valves replaced. There were 81 hospital deaths (6.8%). Risk factors for hospital death included older age (p = 0.0001), higher preoperative left ventricular end diastolic pressure (p = 0.05), longer aortic cross-clamp (AXC) time (p = 0.0001), longer cardiopulmonary bypass (CPB) time (p = 0.0001), female gender (p = 0.02) and previous cardiac surgery (p = 0.0005). Follow-up was 98% complete (3153 pt-ys) at a mean of 2.9 yrs, range 0.1-9 yrs. There were 149 late deaths; 25 (17%) were considered valve-related: 8 prosthetic valve endocarditis (PVE), 4 valve thrombosis (VT), 6 thromboem-bolism (TE), 5 anticoagulant related hemorrhage (ACRH), 1 paravalvular leak (PVL), 1 hemolytic anemia. Overall actuarial survival was 74% (CL: 70%) at 5 yrs postoperatively; actuarial survival for AYR vs. MVR vs. multiple valve replacement did not differ significantly (p = 0.06). Risk factors for late death included older age (p = 0.03), lower preoperative ejection fraction (p = 0.005), longer AXC (p = 0.0001), longer CPB (p = 0.0001), higher preoperative functional class (p = 0.0001) and previous cardiac surgery (p = 0.0003). Late valve-related events included: TE (2.1% pt-yr); ACRH (1.0% pt-yr), PVE (0.5% pt-yr), VT (0.2% pt-yr), PVL (0.9% pt-yr). Actuarial freedom at 5 yrs from TE was 92%; ACRH (94%), PVE (98%), reoperation (98%), PVL (96%), VT (99%). Actuarial freedom from all valve-related events was 75% and actuarial freedom from valve-related deaths was 95% at 5 years. At follow-up, 97% of the survivors were in functional class I and II. We conclude that the low incidence of valve-related events and low mortality supports the continued use of the SJM valve.

*By Invitation

43. Outcome of Mitral Valve Repair in Patients With Preoperative Atrial Fibrillation: Should the Maze Procedure be Combined With Mitral Valvuloplasty?

YEOW L. CHUA, M.D.*, HARTZELL V. SCHAFF, M.D.,

THOMAS A. ORSZULAK, M.D. and

JAMES J. MORRIS, M.D.*

Singapore and Rochester, Minnesota

The low risk of mitral valvuloplasty and encouraging preliminary results of operation to prevent atrial re-entry tachycardia have stimulated interest in combining the procedures for patients (pt) with mitral valve regurgitation (MR). Little is known, however, about the extent to which atrial fibrillation (AF) compromises early and late results of valve repair. Therefore, we reviewed 323 consecutive pts who underwent mitral valve (MV) repair for MR from 1980-91; average age of the 215 men and 108 women was 64 yr (range 14-88 yr), and 224 pt (70%) were in NYHA class III or IV preop. The main indications for operation were severe MR (76%), coronary artery disease (15%), and aortic valve disease (6%). At the time of MV repair, coronary artery bypass grafting was performed in 35% of pt, aortic valve replacement was performed in 7%, and multiple other procedures were performed in 10%. For all pt, 30-day mortality was 2.5% (70% C.L. 1.6% -3.4%), and survivorships at 3 and 5 yr were 81% and 76% respectively. Preoperatively, 215 pt were in sinus rhythm (SR), and 97 pt had AF; in the latter group, 11 pt had onset of AF within 3 mo. preceding MV repair. Comparing pt with preop AF to those with SR, we found no significant difference in operative mortality (3% vs 2%) or 5-yr survival (75% vs 77%). At late follow-up, AF was present in 5% of pt with preop SR, 80% of pt with preop chronic AF, and 0% of pt with preop recent onset AF (p<0.01). The left atrial (LA) size by echocardiography was larger in pt with preop AF compared to those with SR (59 ± 1.4 cm² vs 50.9 ± 0.7 cm², p<0.05). There was, however, no correlation between preop LA size and late AF. Further, age, gender, and associated coronary artery disease did not correlate with presence of AF at late follow-up. Risk of stroke during follow-up was similar in pt with preop SR compared to those with AF.

In conclusion, MV repair should be performed before or soon after the onset of AF in order to maximize the chance of postop SR and avoid long-term anticoagulation with Coumadin. However, the decision for concomitant procedures to control AF should be made with the realization that early and intermediate-term outcome of MV repair in such pt is good, and concomitant operation for supraventricular arrhythmia must have negligible morbidity and no adverse effect on operative mortality.

*By Invitation

44. Glutamate Excitotoxicity - A Mechanism of Neurologic Injury Associated With Hypothermic Circulatory Arrest

J. MARK REDMOND, M.D.*, A. MARC GILLINOV, M.D.*,

KENTON J. ZEHR, M.D.*, MARY E. BLUE, Ph.D.*,

MICHAEL V. JOHNSTON, M.D.*,

JUAN C. TRONCOSO, M.D.*, BRUCE A. RE1TZ, M.D.,

DUKE E. CAMERON, M.D.* and

WILLIAM A. BAUMGARTNER, M.D.

Baltimore, Maryland

Glutamate, the major CNS neurotransmitter, may have potent neurotoxic activity under conditions of metabolic stress. By receptor autoradiography (RA), we have demonstrated that brain regions most vulnerable to injury during prolonged HCA have the highest density of glutamate receptors. To test the hypothesis that such injury could be mediated by GE, we used MK-801, a selective NMDA-glutamate receptor antagonist in a canine model of HCA. Twelve male dogs (20-25kg) were placed on closed-chest car-diopulmonary bypass (CPB), subjected to 2 hours of HCA at 18 °C, and rewarmed to 36°-37°C on CPB. All were mechanically ventilated and monitored for 20 hours before extubation and survived for 3 days. Grp 1 dogs (n = 6) received a pre-HCA IV bolus of MK-801 (0.75 mg/kg) followed by continuous infusion (75ug/kg/hr), resulting in EEC silence. MK-801 was weaned before extubation. Grp 2 dogs (n = 6) received vehicle only. Using a species-specific behavior scale which yielded a neurodeficit score (NDS) ranging from 0 (normal) to 500 (brain dead), all animals were neurologically assessed every 12 hours. Following sacrifice at 72 hrs, brains were examined by RA and histologically for paterns of selective neuronal necrosis and scored blindly from 0 (normal) to 100 (severe injury). Grp 1 dogs had better neurologic function compared to Grp 2, (NDS 21 ± 15 Vs 192 ± 40, p<.001) and had less neuronal injury (7.3 ± 3 Vs 48.3 ± 9, p<.0001). Densitometric RA revealed selective preservation of neuronal NMDA-glutamate receptor expression in Grp 1 only. These results represent the first direct evidence of a role for GE in the development of HCA-induced brain injury and suggest that selective glutamate receptor antagonists may have a neuroprotective role in prolonged periods of HCA.

12:10 p.m. ADJOURN

*By Invitation

WEDNESDAY MORNING, April 28, 1993

9:00 a.m. SIMULTANEOUS SCIENTIFIC SESSION E GENERAL THORACIC SURGERY

Grand Ballroom D

Moderators: Joseph L. Miller, M.D.

Valerie W. Rusch, M.D.

45. Thymomas: Prognostic Factors and Long Term Results of 349 Operated Cases

PHILIPPE LEVASSEUR, M.D.*,

JEAN-FRANCOIS REGNARD, M.D.*,

PIERRE MAGDELEINA T, M.D.*,

PHILIPPE DARTEVELLE, M.D.*,

CHRISTIAN DROMER, M.D.* and

JEAN-FRANCOIS LEVI, M.D.*

Plessis Robinson, France

Sponsored by: Willard A. Fry, Evanston, Illinois

Three hundred forty-nine patients (mean age 49) with thymoma were surgically treated over 26 years. Myasthenia gravis was associated in 209 (60%). MASAOKA staging revealed stage I in 154 (45%), stage II in 76 (22%), stage III in 95 (27%), stage IV in 24 (6%). Among the 325 non metastatic tumors, 277 (85%) were totally resected (all stage I and II, 50% of stage III) and 48 (15% had an incomplete resection or biopsy (50% of stage III). Histological findings* were: "spindle cell" tumors 80 (23%), lym-phocytic rich tumors 86 (25%), epithelial tumors 183 (52%). Post-operative mortality was 2.3% and was not influenced by myasthenia gravis. Postoperative radiotherapy was performed in 15% of stage I and 75% of stage II and totally resected III, and in 85% of non totally resected III. 90% of stage IV were treated by postoperative radiotherapy and/or chemio-therapy. Follow-up was on average 7.5 years and exceeded 10 years in 1/3 of the cases. 8 patients were lost to follow-up. 117 patients died (causes: tumor: 1/3, auto-immune 1/3, miscellaneous 1/3). 21 patients (7.5%) (6 stage I (4%), 8 II (10%) 7 III (15%)) had a recurrence of their thymoma after total excision, and this occurred on average after 6 years (ranged from 2 to 16 years). In calculating by the actuarial method, recurrences were significantly higher in stage III vs II (p<0.001) and in stage II vs I (p<0.01). Overall actuarial survival at 10 years was 65%. Actuarial survival in stage I, II, III and IV was 80%, 71%, 43%, and 30% respectively. No significant difference was seen between stage I and II, or between III and IV. The only significant difference observed was between stage II and III (p<0.001). Regarding the quality of thymoma excision, the 10 year actuarial survival for the group with total excision was 76% vs 28% (p<0.001) in the non totally resected group. Actuarial survival was significantely better in totally resected stage III than in non totally resected III (p<0.001). Similarly, there was no significant difference between stage II and totally resected III, or between non totally resected III and stage IV. Myasthenia gravis and postoperative radiotherapy did not influence the prognosis in univariate analysis. Additionally, the epithelial tumors have a significantly worse prognosis but the multivariate analysis did not confirm this fact, since histology and MASAOKA staging were closely linked.

According to our results, we propose to modify the MASAOKA classification in order to take into account the quality of thymoma excision.

*By Invitation

46. Video-Thoracoscopic Resection Using the Nd:YAG Laser

ROBERT J. KEENAN, M.D.*,

RODNEY J. LANDRENEAU, M.D.,

STEPHEN R. HAZELRIGG, M.D.

and PETER F. FERSON, M.D.

Pittsburgh, Pennsylvania and Milwaukee, Wisconsin

Sponsored by: Hartley P. Griffith, M.D., Pittsburgh,

Pennsylvania

Since January 1991, we have performed 63 thoracoscopic resections, using the Nd:YAG laser, for pulmonary nodular or interstitial disease. Indications included 46 patients with malignancy (27 primary lung; 19 metastatic), 9 with benign nodules, 6 with nodular interstitial processes and 2 with granulomatous disease. There were 30 males and 33 females with a mean age of 62.6 ± 12.5 years. Thirty patients underwent thoracoscopic resection using the NdrYAG laser alone while 33 had lesions resected with a combination of laser and endoscopic stapling. Ten of 27 patients diagnosed with primary lung malignancies subsequently underwent open anatomic resections. Pulmonary reserve of the other 17 patients was deemed inadequate for further resection. Operating time, number of chest tube days, length of hospital stay and complication rate were compared with 72 patients undergoing thoracoscopic resection of nodules using endoscopic stapling alone.

	Laser	Laser + Stapler	Stapler
Or Time (min)	159.4 ± 70.8	160.4 ± 83.6	83.7 ± 51.3*	(p<0.05)
Chest Tube Days	3.4 ± 2.9	4.6 ± 5.3	3.0 ± 1.9	(P = NS)
Hospital Stay (days)	5.3 ± 2.7	6.8 + 5.2	5.4 ± 2.8	(P = NS)
Complications	9/30	9/33	11/72	(P = NS)

Lesions ranged in size from 0.4 to 3.5 cm. Laser resection was performed for lesions deep in the substance of the lung parenchyma or on the effaced surface of the lung; both locations which make stapling alone difficult or impossible. Non-contact laser was used in preference to electrocautery because of the precision of dissection allowing easy identification of vessels which could be clipped and divided safely. Although operating time for laser-assisted procedures was longer (*p<0.05), there were no differences in number of days with chest tubes in place or hospital stay when compared to stapled resections. The complication rate for laser cases was not significantly higher than for stapled resections and consisted primarily of air leaks lasting 2-7 days. The recent use of biologic glue over the raw surface has largely eliminated this problem. There were no bleeding complications or postoperative deaths. Thoracoscopic laser resection is particularly suited for deep lesions and surface nodules where staplers are inadequate. This analysis shows that the Nd:YAG laser is a safe and precise, primary or adjunctive tool for thoracoscopic pulmonary resection.

*By Invitation

47. Thoracoscopic Treatment of Bullous Emphysema Using Sapphire Contact Tip Neodymium Yttrium Aluminum Garnet Laser (Contact YAG): Preliminary Report

AKIO WAKABA YASHI, M.D., HAROLD PETERS, M.D.*,

NARINDAR SINGH, M.D.*, GARY BENNETT, M.D.*,

GREGORY BARNES, M.D.*, RICHARD FUJITA, M.D.*

and JANE CALMESE, R.N.*

Orange, California

We initiated the thoracoscopic treatment of bullous emphysema using carbon dioxide (CO₂) laser three and a half years ago with an excellent result. However, it was found ineffective for certain types of bullae and its articulated arm was difficult to maneuver. Therefore, the current study was undertaken to investigate the efficacy of sapphire contact Nd:YAG laser (Contact YAG). From September 21, 1992 to September 18, 1992, 128 patients (95 males & 33 females) with severe bullous emphysema with chronic obstructive pulmonary disease were treated by Contact YAG. Patient selection was based on symptoms (dyspnea), forced exploratory volume for one second (FEV,), and chest computed tomography (CT). No patients were denied because of the severity of illness. Age ranged from 39 to 79, mean being 65.71 ± 7.38. Seventy-eight patients were prednisone dependent, 55 oxygen dependent, 42 wheelchair- or bed-bound, 3 had antitrypsin deficiency and 2 had infected bullae. FEV, varied from 8 to 72% of predicted values, the mean being 22.69 ± 11.58. CT showed giant compressive bullae (type I) in 3, diffuse bullae (type III) in 98 and a combination (type IV) in 27 cases. Type III bullae were contracted by contact YAG laser round probe and Type I and IV bullae were excised by contact YAG laser scalpel. In adition, the bronchial communications were closed by sutures and redundant bullae plicated. The anesthesia time ranged from 1.5 to 10.1 hours, the mean being 4.84 ± 1.54. The ventilatory support ranged from 3 to 504 hours, the mean being 23.66 ± 56.88 hours. The air leak persisted for 3 to 64 days, the mean being 18.59 ± 13.64 days. Seven patients required repeated thoracoscopy for closure of bronchopleural fistulae. Five patients died, thus the overall mortality rate was 4%. Clinical improvement was noted in all but two; 21 (38%) patients were off oxygen and 26 (63%) could walk without wheelchair. In conclusion, thoracoscopic ablation of bullae using a sapphire contact tip Nd:YAG laser is an effective treatment with a reasonable risk for bullous emphysema.

*By Invitation

48. Thoracoscopic Wedge Excisions for Indeterminate Pulmonary Nodules

MARK S. ALLEN, M.D.*, CLA UDE DESCHAMPS, M.D.*,

ROBERTA E. LEE, M.D.*, VICTOR F. TRASTEK, M.D.

and PETER C. PAIROLERO, M.D.

Rochester, Minnesota

From June 1991 to July 1992, 119 patients (53 males, 66 females) underwent 121 video thoracoscopic surgical (VTS) procedures for indeterminate pulmonary nodules (IPN). Median age was 64 years (range 20-85). Thoracotomy was performed in 29 patients (24%) after thoracoscopy only because the nodule could not be located in 15 patients, appeared malignant in 5, or for other technical reasons in 9. Incisional biopsy revealing metastatic carcinoma made wedge excision unnecessary in 4 patients. Thoracotomy was also required following an unsuccessful attempt at VTS wedge resection in 3 patients. Eighty-five patients underwent 96 wedge resections using VTS. Twenty-one (25%) of these 85 patients were opened, 13 to perform formal lung resection following a diagnosis of bronchogenic carcinoma, 4 for an initial nondiagnostic pathology report, 2 to locate a second nodule, and 1 each for a positive metastatic cancer margin, and stapler malfunction. The pathology of the remaining wedge excisions was granuloma in 29, metastatic cancer in 25, other benign lesions in 9, hamartoma in 8, and lymphoma in 3. In those undergoing VTS alone, there was no mortality, and there were 4 (6.2%) complications. Postoperative analgesic requirements were less in the VTS only group when compared to the open group. The average postoperative hospital stay in the VTS only group was 4 days.

We conclude that VTS wedge resection is a safe and effective procedure in carefully selected patients with IPN. A significant number (42%) required an open procedure to ensure an adequate resection of malignancy or to accomplish a safe operation.

10:20 a.m. INTERMISSION - VISIT EXHIBITS

*By Invitation

11:05 a.m. SIMULTANEOUS SCIENTIFIC SESSION E GENERAL THORACIC SURGERY Grand Ballroom D

49. Short Segment Intestinal Interposition of the Esophagus

DOUGLAS J. MATHISEN, M.D.*,

HENNING A GAISSERT, M.D.*, HERMES C. GRILLO, M.D.,

JOHN C. WAIN, M.D.*, ASHBY C. MONCURE, M.D.,

RONALD A. MALT, M.D.* and

LESLIE W. OTTINGER, M.D.*

Boston, Massachusetts

Esophageal replacement remains a challenge. For some conditions the stomach is not a suitable substitute. Short segment colon and jejunal interposition are alternative conduits, however, limited information is available on the results of their use. Between 1971 and 1991, 41 patients underwent short segment interposition of the esophagus with jejunum or colon. Indications were failed antireflux procedures (21 patients), nondilatable stricture (11), achalasia (2), Barrett's esophagus (2), hemorrhagic esophagitis after esophagogastrectomy (1), motility disorder (1), instrumental perforation (1), carcinoma (1), and leiomyosarcoma (1). Thirty-one patients (75.6 percent) had prior surgical procedures. Eleven males and 11 females (mean age 56.9 years) had colon grafts, 12 males and 7 females (mean age 65.0 years) underwent jejunal interposition. Median hospital stay was 17 days for colon and 21 days for jejunum. Major complications after colon interposition consisted of pneumonia (3 patients), sepsis (1), ARDS (1), graft perforation (1), sub-phrenic abscess (1), chylothorax (1), pulmonary edema (1), pulmonary em-bolus (1), and DVT (1), and in-hospital mortality was 4.5 percent (sepsis-1). Major complications following jejunal interposition included pneumonia (3 patients), graft necrosis (1), MI (1), iatrogenic gastric perforation (1), and in-hospital mortality was 10.5 percent (graft necrosis-1, MI-1). One anastomotic leak was contained. Two colon and one jejunal grafts required late revision. One or more dilatations were performed after 4 jejunal and 5 colon interpositions. Mean follow-up for 36 patients is 77.9 months. Twenty-two patients responded to a questionnaire. All tolerate a regular diet. Dysphagia is mild (8) or absent (14). Regurgitation is described as mild in 11 and severe in 4 patients. Six patients underwent manometry and barium food study. Two colon segments were aperistaltic by manometry and emptied by gravity. Three jejunal interpositions were hypoperistaltic by manometry with slow emptying of contrast and 1 was aperistaltic with a distended afferent loop on fluoroscopy. When stomach is not available, successful palliation of swallowing can be accomplished with either jejunum or colon. Surgeons involved in the management of esophageal disease should be familiar with the demanding technical details of both procedures.

*By Invitation

50. Extended Esophagectomy in the Management of Esophageal Carcinoma of the Upper Thoracic Esophagus

WICKII T. V1GNESWARAN, M.D.*,

VICTOR F. TRASTEK, M.D., MARK S. ALLEN, M.D.*,

CLAUDE DESCHAMPS, M.D.* and

PETER C. PAIROLERO, M.D.

Rochester, Minnesota

Resection of cancers of the upper thoracic esophagus often require a preliminary thoracotomy to accomplish resection. Between January 1985 and July 1992, 50 consecutive patients underwent extended esophagectomy for cancer of the upper thoracic esophagus where the neoplasm was resected through a concommitant laporatomy, right thoracotomy, and cervical incision. There were 39 males and 11 females. Ages ranged from 40 to 80 years (mean 63 +/- 9.5 years). Thirty-three patients (66%) had squamous cell carcinoma, and 17 (33%) had adenocarcinoma arising in Barrett's esophagus. Complications occurred in 31 patients and included pneumonia in 19 patients; anastomotic leak in 17, vocal cord paralysis in 13, atrial ar-rythmia in 10, wound infection in 5, renal failure in one, and postoperative bleeding in one. Four patients required tracheostomy. There was one perioperative death (2%). Median survival was 1.6 years. Twenty-five patients are currently alive, 22 without evidence of cancer. Cause of death was recurrent disease in 20 patients. The overall two- and four-year actuarial survival was 48% and 31%, respectively. Survival data by stage will be presented. Nine patients developed late dysphagia; 4, gastroesophageal reflux; and 3, symptoms of dumping. Although associated with significant morbidity, we conclude that extended esophagectomy is the procedure of choice for neoplasms of the up