WEDNESDAY MORNING, APRIL 26, 1995
7:00 am FORUM SESSION II
Grand Ballroom, Sheraton Boston
Hotel
Moderators: Robert A. Guyton, M.D.
Shukri F. Khuri, M.D.
F9. THE EXPRESSION OF TNFα AND
CHEMOKINES (ENA-78 AND GROα) DURING ISCHEMIA/ REPERFUSION INJURY ASSOCIATED
WITH LUNG TRANSPLANTATION
K..E. Magliato, M.D.*, D.L.
Swiderski, Ph.D.*,
S.L. Kunkel, Ph.D.*, C.A. Wilke,
B.S.*, M.D. Burdick, B.S.*, G.M. Deeb, M.D. and R.M. Stricter, M.D.*
Akron, Ohio and Ann Arbor,
Michigan
The reimplantation response or
ischemia/reperfusion injury is potentially an important cause of morbidity
during lung transplantation. While a number of cellular events are involved in
this response, the neutrophil appears to play a pivotal role in mediating lung
injury during reimplantation. The mechanisms that lead to neutrophil
sequestration and activation are complex and have not been fully elucidated. We
postulated that the generation of the early response cytokine, tumor necrosis
factor alpha (TNFα), and the chemokines, epithelial cell neutrophil
activating protein (ENA-78), and growth related oncogene alpha (GROα ),
would be significantly elevated during the reimplantation response and be
associated with maximal neutrophil sequestration and subsequent lung injury. To
test this hypothesis, we evaluated pulmonary microvascular permeability as
index of injury, neutrophil influx , and expression of TNFα, ENA-78, and
GROα during the reimplantation response using a rat orthotopic single-lung
syngeneic transplant model. Cytokine expression in plasma, lung tissue
homogenates, and bronchoalveolar lavage (BAL) at 4, 12, 24, 36, and 48 hours
post-reimplantation was measured by specific ELISAs (n=30). Cytokine levels
from the transplant recipient animals were similar to sham operated control
animals until 24 hrs post-reimplantation. At 24 hrs post-reimplantation, TNFa,
ENA-78, and GROα were all significantly elevated (2-fold) from the lung
tissue homogenates of the transplant recipients, as compared to sham operated
controls. The concentrations of all cytokines returned to levels similar to the
sham operated animals by 48 hours. Pulmonary neutrophil sequestration, as
evaluated by BAL cell counts, paralleled the changes in lung tissue cytokine
levels. At 24 hours, neutrophil absolute and relative levels were higher in
transplant recipients (6.5± 4.4 x 105, 69.7±5.8% of the total) than
in sham operated controls (2.4±1.1 x 105, 12.3±5.7% of the total)
(p=.002). The findings of BAL neutrophil levels were corroborated by elevated
levels of myeloperoxidase activity from transplanted lung tissue homogenates
(100.8±22.8) as compared with sham controls (35.1±8.1) (p=.02). Using Evan's
blue dye as marker of pulmonary microvascular permeability, transplant
recipients at 24 hours post-reimplantation demonstrated a 2.5-fold greater
index of lung permeability, as compared to sham operated control animals
(p=.01). In addition, transplanted animals pretreated with neutralizing TNF
antisera showed a 50% decrease in lung injury by Evan's blue dye lung
permeability assessment. These findings suggest that the temporal expression of
TNFcc, ENA-78, GROa correlates with maximal neutrophil sequestration and lung
injury associated with the reimplantation response and neutralizing TNF
antisera has a protective role in ischemia/reperfusion injury.
*By invitation
F10. THERAPEUTIC ANGIOGENESIS: ACIDIC
FIBROBLAST GROWTH FACTOR ACCELERATES COLLATERAL VESSEL FORMATION AND
REVASCULARIZATION OF ISCHEMIC TISSUES
Todd K. Rosengart, M.D.*, Martin
A. Duenas, B.S.*, Qing-Xue Zhang, Ph.D.*, Karl H. Krieger, M.D. and O. Wayne
Isom, M.D.
New York, New York
Angiogenesis,
the growth of new blood vessels, is thought to be an important biological
mechanism allowing for the revascularization of ischemic tissues. Acidic
fibroblast growth factor (aFGF) is a potent stimulant of angio-genesis that may
prove useful in accelerating collateral vessel development following vascular
occlusion. We therefore assessed the ability of aFGF to enhance angiogenesis
and improve perfusion in the setting of acute ischemia. Ligation of the left
common femoral artery was performed in the rat followed by the daily
transcutaneous injections into the ischemic hind limb region of saline (1ml) or
recombinant human aFGF (1 mcgm in 1 ml saline) for 10 days following ligation
(n=4). Following the treatment period, 2 x 106 color micro-spheres
were injected via the infrarenal abdominal aorta and the relative perfusion of
the ligated limb versus the unligated, contralateral control limb was
determined from the microsphere counts per gram of tissue harvested from each
limb. Relative perfusion of the ligated limb in the aFGF-treated animals was 62
± 16% (mean ± SEM) of that to the unligated, contralateral control limb
compared with 10 ± 3% relative perfusion in the saline-treated animals
(p=0.004). These results were confirmed by histologic analysis of hind limb tissue
specimens, which demonstrated 27 ± 2 vs 4 ± 1 vessels per high power field in
the aFGF and saline-treated animals, respectively (p=0.001). Proliferating cell
nuclear antigen (PCNA) analysis was utilized to assess mitogenic activity and
demonstrated that the percentage of PCNA-labelled cells per total cell nuclei
was 68 ± 4% vs 5 ± 1% in the two respective groups (p<0.001). The six-fold
increase in perfusion noted in these studies, confirmed by analysis of
vascularization and cell replication, suggest that exogenous aFGF
administration may represent a useful means of enhancing collateral vessel
growth and relieving acute ischemia. The administration of aFGF may potentially
allow the revascularization of myocardial or other tissues not salvageable by
bypass procedures or other conventional means.
*By invitation
F11. MYOBLAST TRANSPLANTATION IN THE PORCINE
MODEL. A POTENTIAL TECHNIQUE FOR MYOCARDIAL REPAIR
Clifford H. Van Meter, Jr.,
M.D.*, Frank Smart, M.D.*, William Claycomb, Ph.D.*, Joseph DelCarpio, Ph.D.*
and John L. Ochsner, M.D.
New Orleans, Louisiana
The increasing
shortage of organ donors continues to fuel the search for other methods to
manage heart failure. The use of transgenic cells transplanted in syngeneic
rodents has shown modest success, but allogeneic and xenogeneic transplants
have not been uniformly successful. To assess the feasibility of xenogeneic and
allogeneic myoblast transplantation, six adult swine underwent transplantation
of murine atrial tumor cells (xenogeneic) and neonatal porcine (allogeneic)
into the left ventricular wall. A subsequent seventh animal underwent
transplantation of human neonatal myoblasts (16 weeks of age). Following
general anesthesia, isolated cells were injected along the anterior and
posterior wall of the porcine left ventricle (6 to 8 sites per animal). All the
animals were immunosuppressed with cyclosporine and prednisone and were
followed for one month post-injection at which time they were sacrificed.
In all injected
sites, the transplanted cells proliferated within the host myocardium with no
significant rejection. CPK MB isoenzymes did not increase after the procedure
indicating that there was no damage to the host myocardium from the injection
of cells. Moreover, transplant cells formed close associations with host
myocytes that resembled intercalated discs on electron mycroscopy, and were
composed of PAN cadherin on immuno-fluorescent staining. These cells also
contained myofibrils and other cell architecture that resembled normal AT-1 or
neonatal myocytes. Additionally, these cells produced angiogenic factors
resulting in a proliferation of the surrounding microvasculature. In
conclusion, these findings indicate successful xenogeneic and allogeneic
myocyte cell transplantation in a large animal model. These experiments set the
stage for future studies to test the ability of these cells to form a
syncytium, to contract, and potentially repair failed myocardium.
*By invitation
F12. EFFICIENT CARDIAC GENE TRANSFER BY
INTRA-CORONARY INFUSION OF ADENOVIRUS VECTOR MEDIATED REPORTER GENE IN
TRANSPLANTED MOUSE HEART
Jeongryul Lee, M.D.*, Alistair I.
Fyfe, M.D.*, Hillel Laks, M.D., Davis C. Drinkwater, M.D., Yuji Shiraishi,
M.D.* and Paul Chang, B.S.*
Los Angeles, California
Gene transfer
into the coronary arteries may offer an opportunity to modulate alloreactivity
after cardiac transplantation. In the present study, we perfused the coronary
arteries of donor mouse hearts with 107 pfu (200 |aL) of a
recombinant adenovirus containing P-galactosidase encoding gene (AdCMV P gal)
just prior to harvesting to demonstrate the feasibility, efficacy, and safety
of adenovirus mediated in vivo transfer. The donor hearts were transplanted
into the abdomen of the recipient mice of the same strain (BIO. BR). Both the
grafts and recipient hearts were harvested at 3, 7, 15 and 30 days (n=6 in each
group) after transplantation and P-galactosidase activity was assessed by
immunohistochemistry. All grafts were functioning adequately at the time of
harvest and P-galactosidase expression was seen throughout the myocardium,
epicardium, and the surrounding coronary arteries. There were no significant
differences in expression at least up to 30 days after transplantation.
Staining was not seen in recipient hearts or sham control isografts (n=6) which
were sacrificed 7 days after infusion of saline into the coronary arteries.
This study revealed that intracoronary adenovirus mediated gene transfer is an
efficient and feasible method for transfecting genes, with widespread
expression, and there does not appear to be significant early cardiac graft
dysfunction associated with the use of adenovirus. This approach may allow
modification of graft immunogenicity in the future by allowing the production
of therapeutic proteins that inhibit or delay the development of cardiac
allograft vasculopathy.
*By invitation
F13. INTRATHYMIC STEM CELL TRANSPLANTS
PROLONGSKIN GRAFT SURVIVAL IN UNRELATED PRIMATES
Margaret D. Allen, M.D., Hiroji
Akimoto, M.D.*, John T. Weyhrich, D.V.M.*, Karen A. Nelson, Ph.D.*, Robert
Thomas, B.S.* and Robert G. Andrews, M.D.
Seattle, Washington
The intrathymic
implantation of stem cells in transplant recipients may resolve several
problems limiting the attainment of tolerance to transplanted organs. 1)
Peripheral blood microchimerism has been associated with reduced rejection in
clinical liver and renal transplantation but peripheral infusion of donor
marrow to induce chimerism carries a risk of graft-versus-host disease (GVHD).
Recent bone marrow transplants in primates suggest that stem cell fractions may
result in less GVHD. 2) Intrathymic implantation of lymphocytes, splenocytes,
class II peptides, and even islets in rodents pre-treated with myeloablation or
anti-lymphocyte globulin can extend subsequent donor organ or skin graft
survival, but hematopoietic microchimerism has not been reported. Stem cells
might provide a self-perpetuating source of donor antigens. 3) If suppressor
mechanisms are operative, less, rather than more, immunosuppression may be
beneficial. This study examines whether the intrathymic implantation of donor
CD34+ enriched marrow (97% CD34+) might produce hematopoietic chimerism and
induce tolerance to donor-derived grafts in unrelated primates with or without
immunosuppression.
Four juvenile
female baboons underwent intrathymic transplantation of CD34+ enriched marrow
(1 x 106 cells) from unrelated male baboon donors through a left
thoracotomy approach. Peripheral blood was sampled at biweekly intervals for
the presence and persistence of donor cells using PCR for Y chromosome
determinants. Two recipient animals were treated with standard triple drug
immunosuppression consisting of cyclosporine, azathioprine, and steroids, in
doses equivalent to the clinical cardiac transplant protocol. No myeloablative
therapy or anti-lymphocyte serum induction was used. Two other recipients
received no immunosuppression. All 4 recipients, both with and without
immunosuppression, developed peripheral blood microchimerism within 2 weeks
which is still persistent at 9-16 months. No clinical evidence of GVHD was
observed.
To test whether
the implantation of intrathymic stem cells resulted in tolerance, two further
juvenile female baboons were implanted with male donor CD34+ marrow without
recipient immunosuppression. Chimerism was detected in both animals. Three
months following the intrathymic implants, 9 skin grafts were placed on each
recipient: 3 from autologous skin, 3 from the stem cell donor, and 3 from a
third party baboon. Autologous grafts were incorporated without rejection.
Third party grafts sloughed at 24 days post-transplant and, in both recipients,
the grafts from the stem cell donor persisted DNA. Repetition of the skin
grafts again demonstrated prolongation of the stem cell-donor over the third
party-donor grafts.
These results
demonstrate that: l)the intrathymic implantation of donor CD34+ enriched marrow
can induce peripheral microchimerism in non-human primates with or without
immunosuppression; 2) 1 x 106 CD34+ cells is sufficient to induce
peripheral chimerism; 3) donor-specific skin graft, prolongation was achieved;
and 4) graft versus host disease was not observed. These findings have current
applications in the field of thoracic transplantation tolerance as well as
future potential in the treatment of genetic deficiency diseases of the
newborn.
Nina S. Braunwald Career
Development Award Recipient
*By invitation
F14. INHIBITION OF INDUCIBLE NITRIC OXIDE
AMELIORATES RAT LUNG ALLOGRAFT REJECTION
Takeshi Shiraishi, M.D.*, Neil K.
Worrall, M.D.*, Steven R. DeMeester, M.D.*, Jon H. Ritter, M.D.*, Thomas P.
Misko, Ph.D.*, T. Bruce Ferguson, M.D., Joel D. Cooper, M.D. and G. Alexander
Patterson, M.D.
St. Louis, Missouri
Inhibition of the production of nitric oxide (NO)
by inhibition of inducible nitric oxide synthase (iNOS) has recently been
demonstrated to attenuate the pathogenesis of acute cardiac allograft
rejection. This study examined the effect of inhibition of NO production on
rejection in a rat lung transplant model. Syngeneic (F344 to F344) (n=7) and
allogeneic (Brown Norway to F344 recipient) (n=8) left lung transplants were
performed. In this latter strain combination complete rejection occurs by
postoperative day 8. Using the same allogeneic combination, a third group of
animals (n=9) underwent allotransplantation and received aminoguanidine (a
specific iNOS inhibitor) 200 mg/kg IP q6h from transplantation until sacrifice
on postoperative day 7 (POD-7). NO production was demonstrated by measuring
serum nitrite/nitrate levels (stable end products of NO metabolism). Allograft
serum nitrite/nitrate levels [16.5 ± 1.7mM, n=4 (p<.01 by
ANOVA)] were elevated above normal control (8.0 ± 1.0 mM, n=3) and isograft
levels (9.0 ± 1.4 mM,
n=4) on postoperative day 4 (POD-4), indicating that NO is produced during lung
allograft rejection. Aminoguanidine treatment prevented the increased serum
nitrite/nitrate levels in the allografts on POD-4 (9.8 ± 1.0 mM;
p<0.01 vs untreated allografts). The effect of iNOS inhibition on acute
rejection was determined by using three scoring systems. Severity of rejection
was evaluated using a radiographic score (Aeration Score; 0=opaque to 6=normal
appearing lung). The histologic rejection grade was determined at sacrifice on
POD-7 using the International Working Formulation (I.W.F. score: 0=normal to
4=diffuse infiltration of mononuclear cells) and Prop's scoring system
(0=latent phase to 3=destruction). Aminoguanidine treatment significantly
attenuated acute rejection as determined radiographically [AS= 4.1 ± 1.4 vs 1.8
± 0.9 for untreated allografts on POD-6 (p<.05) and 3.9 ± 1.5 vs 0.6 ± 0.5
on POD-7 (p<.01)]. Aminoguanidine treatment also significantly ameliorated
the histologic degree of rejection as determined at sacrifice on POD-7 [2.6 ±
0.2 vs 3.8 ± 0.5 for untreated allografts by IWF score (p<.005) and 1.3 ±
0.4 vs 2.6 ± 0.7 by Prop's score (p<.005)]. These results demonstrate that
NO is produced during acute lung allograft rejection and that selective
inhibition of the inducible isoform of nitric oxide synthase significantly
attenuated acute rejection. NO production may serve as a marker of early
rejection and selective inhibition of iNOS may be a novel therapeutic modality
in the management of acute lung allograft rejection.
*By invitation
F15. THE EFFECT OF N-co-NITRO-L-ARGININE ON
PULMONARY VASCULAR TONE IN THE MATURING NEWBORN PIG
Patrick W. Domkowski, Ph.D.*,
John T. Cockerham, M.D.*, Peter A. Kot, M.D.*, Jeffrey L. Myers, M.D.*, Yi-Ning
Wang, M.D.*, Robert B. Wallace, M.D. and Richard A. Hopkins, M.D.
Washington, DC
Current
therapeutic modalities for treatment of newborn pulmonary hypertensive crisis
include the administration of nitric oxide (endothelium derived relaxing
factor, EDRF). However, few data are available on the role of endogenously
produced EDRF in the modulation of newborn pulmonary arterial tone. We
investigated the acute effects of a 10-minute intravenous infusion of
N-oo-nitro-L-arginine (L-NA), a potent competitive inhibitor of EDRF synthase
on the pulmonary vascular response, in 48-hour and 2-week-old anesthetized
open-chest Yorkshire pigs. Fourier analysis of high fidelity main pulmonary
artery pressure (PAP) and flow (PAF) waveforms was employed to distinguish
between proximal and distal pulmonary arterial responses to L-NA. Input mean
impedance (Zm, reflective of distal vasocon-striction) and
characteristic impedance (Z0, reflecting proximal arterial
disten-sibility) were calculated. Pulmonary vascular resistance (PVR) was also
calculated. Data were collected at baseline and during intravenous infusion of
L-NA.
|
|
PAP
|
PAF
|
PVR
|
Zm
|
Z0
|
|
48-hour-old pigs (n=8)
|
17.0 ± 1.1
|
4.0 ± 0.6
|
5171 ± 805
|
6343 ± 806
|
2073 ± 418
|
|
L-NA (100mg/kg/min) infusion
|
17.6 ± 1.2
|
4.0 ± 0.5
|
5189 ± 1058
|
6529 ± 1043
|
2033 ± 466
|
|
2-week-old pigs (n=7)
|
13.7 ± 1.1
|
8.4 ± 1.0
|
810 ± 137
|
2302 ± 251
|
282 ± 40
|
|
L-NA (100mg/kg/min) infusion
|
18.0 ± 1.4*
|
8.7 ± 0.7
|
1519 ± 239*
|
2900 ± 255*
|
234 ± 21
|
|
mean ± S.E.M. *p<0.05 v.
corresponding baseline; PAP = mmHg, PAF = ml/sec, units = dyne sec cm-5
|
Baseline hemodynamic parameters
were significantly diminished in 2-week-old pigs, reflecting the expected
decrease in both proximal and distal pulmonary arterial vasoconstriction with
maturation. L-NA produced no significant pulmonary hemodynamic changes in
48-hour-old pigs. However, in 2-week-old pigs, L-NA caused a significant
pulmonary arteriolar vasoconstriction. L-NA infusion did not cause any
significant alterations in zq in
either group. These data indicate that endogenously produced EDRF modulates
distal pulmonary arterial tone in 2-week-old pigs, but not in 48-hour-old pigs.
Pulmonary hypertensive crisis of the newborn may reflect an inability of the
pulmonary endothelium to synthesize and release nitric oxide in quantities
sufficient enough to modulate pulmonary vascular tone.
*By invitation
F16. ELUCIDATION OF A TRIPARTITE MECHANISM
UNDERLYING THE IMPROVEMENT IN CARDIAC TOLERANCE TO ISCHEMIA BY COENZYME Q10
PRETREATMENT
Juan A. Crestanello, M.D.*,
Joseph Kamelgard, M.D.*, David M. Lingle, M.D.*, Svend A. Mortensen, M.D.* and
Glenn J.R. Whitman, M.D.
Philadelphia, Pennsylvania and
Copenhagen, Denmark
CoQ10,
involved with mitochondrial ATP production, is also a powerful antioxidant. We
hypothesize that CoQ10 pretreatment protects myocardium from
ischemia reperfusion injury by both its ability to increase aerobic energy
production and by its ability to protect creatine kinase (CK) from oxidative
inactivation during reperfusion.
Isolated hearts
(n=6/group) from rats pretreated with either CoQ10 20 mg/kg i.m. and
10 mg/kg i.p. (CoQ) or vehicle only (CTRL) 24 and 2 hours prior to the
experiment were subjected to 15 minutes of equilibration (EQ), 25 minutes of
ischemia, and 40 minutes of reperfusion (RP). Developed pressure (DP), ±dP/dt,
myocardial oxygen consumption (MVO2), and myocardial aerobic efficiency
(DP/MVC^) were measured. In parallel groups of hearts, 31P NMR
spectroscopy was used to determine P-ATP and PCr concentrations. Hearts were
assayed for myocardial CK activity at end RP. Values are expressed as mean ±
SEM with t-test used for statistical evaluation.
|
|
Reperfusion 40
|
PCr
|
ATP
|
|
|
DP
(% EQ)
|
+dP/dt
(% EQ)
|
-dP/dt
(% EQ)
|
CK
IU/g V
|
DP/MVOZ
mmHg/(m O2/min/g V
|
EQ
(%MDP)
|
RP40
(%MDP)
|
EQ
(%MDP)
|
RP40
(%MDP)
|
|
CTRL
|
37 ± 4
|
37 ± 5
|
36 ± 5
|
391 ± 10
|
0.621 ± 0.069
|
35 ± 3
|
23 ± 4
|
33 ± 3
|
11 ± 2
|
|
CoQ
|
62 ± 2**
|
64 ± 2**
|
61 ± 2**
|
435 ± 17*
|
0 835 ± 0 076*
|
49 ± 3**
|
45 ± 4**
|
49 ± 2**
|
18 ± 3*
|
(MDP: Methylenediphosphonic
acid standard) *p<0.05
vs Control **p<0 005 vs
Control
CoQ10 pretreatment
improves myocardial function after ischemia reperfusion. This results from a
tripartite effect: 1) higher ATP and PCr concentrations initially and during
reperfusion, 2) improved myocardial aerobic efficiency during reperfusion, and
3) protection of CK from oxidative inactivation during reperfusion with an
improved bioenergetic profile.
*By invitation
F17. INDUCED IMMUNOLOGIC UNRESPONSIVENESS
INHIBITS CARDIAC GRAFT ARTERIOSCLEROSIS
Yong T. Shin, M.D.*, Mohamed H.
Sayegh, M.D.*, Lauri R. Wyner, B.A.*, Morris J. Karnovsky, M.B., B.Ch.* and
David H. Adams, M.D.*
Boston, Massachusetts
Sponsored by: Lawrence H.
Cohn, M.D., Boston, Massachusetts
Chronic
rejection, manifested by the development of graft arteriosclerosis, remains the
leading cause of late death in cardiac transplant recipients. Immunologic
mechanisms have been implicated in both experimental and clinical studies, yet
the pathogenesis and therapy of chronic allograft rejection remains poorly
defined. Recent studies have shown that intrathymic (i.t.) injection of donor
cells or processed allo-MHC antigens with or without transient
immunosuppression induces specific systemic T cell tolerance and prevents acute
allograft rejection in several experimental trasnplantation models. In this
study we examined the effects of i.t injection of donor cells with or without
systemic anti-lymphocyte serum (ALS) on the development of chronic rejection in
the Lewis-to-F344 rat cardiac allograft model. Recipients were divided into 4
groups: control group A was pre-treated with saline i.t., group B received
donor (Lewis) splenocytes i.t. (2x106), group C was pre-treated with
a one-time dose of ALS (1 ml) via intraperitoneal injection (i.p.), and group D
received both the splenocytes i.t. and a one-time dose of ALS i.p. two weeks
prior to transplantation. Allografts were followed by daily palpation and
graded from 0-4 (grade 0=non-palpable, grade 4=normal heartbeat). Graft
survival on post-op day 90 for all three treated groups was 100% vs. 33% for
the control (n=6/group), and mean heartbeat grade for the three treated groups
(B=2.0±0.41, C=2.83±0.17, D=2.67±0.21) was significantly higher (p<0.01) vs.
the control group (A=0.4±0.24). Histologic and immunocytochemical analysis of
90-day old grafts revealed the following results (*(p<0.02, **p<0.003vs
Control):
|
Groups
|
Inflammation
|
% Vessels Diseased
|
% Luminal Occlusion
|
Intima:Media Ratio
|
|
Control (A)
|
severe
|
89 ± 1
|
64 ± 5
|
0.97 ± 0.33
|
|
Splenocyte only (B)
|
moderate-severe
|
79 ± 8
|
57 ± 7
|
0.68 ± 0.16
|
|
ALS only (C)
|
minimal
|
25 ± 3**
|
8 ± 3**
|
0.09 ± 0.04*
|
|
Splenocyte+ALS (D)
|
minimal
|
27 ± 3**
|
8 ± 3**
|
0.07 ± 0.03*
|
Conclusions: (1) Treatment with donor splenocytes
i.t. alone partially suppresses the immune response, prolonging graft survival
and preserving function without inhibiting graft inflammation or
arteriosclerosis. (2) The induction of systemic unresponsiveness with ALS i.p.
or splenocytes i.t. plus ALS i.p. markedly reduces inflammation and inhibits
graft arteriosclerosis, suggesting the development of therapies resulting in
better control of the immune response remains the key to ameliorating this disease
process.
Alton Ochsner Research Scholar .
*By invitation
F18. MOLECULAR GENETIC DIFFERENTIATION
BETWEEN PRIMARY LUNG CANCER AND LUNG METASTASES OF OTHER TUMORS
Daniela Kandioler, M.D.*, Gerhard
Dekan, M.D.*, Adelheid End, M.D.*, Michael Mttller, M.D.*, Michael Gnant,
M.D.*, Eva Pasching*, Christine Mannhalter, Ph.D.*, Franz Eckersberger, M.D.*,
and Ernst Wolner, M.D.
Vienna, Austria
When single
pulmonary tumors are observed in patients with history of other cancer,
differentiation between metastasis and second primary lung cancer is crucial
for appropriate therapy. Particularly in low differentiated tumors this
determination by means of histology alone may be difficult or impossible even
with the help of immunochemistry. Implicating that p53 mutations are conserved
in metastases, we hypothesized that a genetic fingerprinting using the p53 gene
could be a valuable tool in differentiating between metastases and second
primary carcinomas since the p53 gene is frequently affected by various
mutations in many different types of human carcinomas.
Out of 267 resected lung tumors we analysed 9 cases
of solid lung tumors whose origin could not exactly be defined histologically.
As a control we used tumor material of a patient with adenocarcinoma of the
lung and histologically defined brain and lymphnode metastases.
Cases
|
History of
|
Lung Tumor
|
|
5
|
colon carcinoma
|
adenocarcinoma
|
|
1
|
breast cancer
|
adenocarcinoma
|
|
1
|
soft tissue sarcoma
|
undifferentiated blastoma
|
|
1
|
renal & thyroid cancer
|
clear cell carcinoma
|
|
1
|
head and neck
|
squamous cell carcinoma
|
We extracted
DNA from the shock frozen tissue of the unclassified lung tumors, from the
paraffin embedded tissue of the "past primary cancers" and from peripheral
blood of the patients. Exons 2 to 11 of the p53 gene were amplified separately
by polymerase chain reaction (PCR) and directly sequenced. In all cases the
presence of germline mutations could be excluded by analysis of the peripheral
blood. The p53 mutation detected in the control tumor proved to be conserved in
the lymph node as well as in the brain metastasis.
In two cases the lung tumor was identified as
(second) primary lung cancer since the genetically compared tumors exhibited
different mutations. In five cases the lung tumors proved to be metastases
exhibiting the identical p53 mutation as their "primary." In one case the lung
tumor could be identified as metastases from renal cancer whereas a thyroid
cancer metastasis could be excluded. One case remained inconclusive since no
p53 mutation could be found in any tissue. Thus, due to genetic analysis using
the p53 gene, correct surgical treatment could be approved in six cases
regarded as metastatic disease of the lung, whereas further pulmonary surgery
was mandatory in two cases identified as second primary lung cancer.
We conclude
that analysis of p53 mutations is a valuable tool in the exact diagnosis of
metastases and recurrent tumors which are difficult to classify by standard
methods. Since the information about tumor origin is essential in assessing an individual
patient's treatment strategy, these results are clinically relevant.
*By invitation
9:30 am SIMULTANEOUS SCIENTIFIC SESSION
D ADULT CARDIAC SURGERY
Grand Ballroom, Sheraton Boston Hotel
Moderators: D. Glenn Pennington, M.D.
Robert L. Hardesty, M.D.
41. REFERRAL SOURCE AS A RISK FACTOR FOR
CORONARY BYPASS SURGERY: HMO VS. PRIVATE PRACTICE
Albert Starr, M.D., Aftab Ahmad,
M.D.* Anthony Furnary, M.D.*, Guo Wei He, M.D.*, Jeffrey Swanson, M.D.* and
Gary Grunkemeier, Ph.D.*
Portland, Oregon
We began
performing coronary bypass surgery (CBS) for a large HMO in 1974, as the sole
provider of their cardiac surgery. The HMO system entails pre-intervention,
multi-disciplinary screening conferences and is absent of self-referral and
personal financial incentives. Since 1985, the operative mortality for HMO
patients has consistently been lower than for private patients. There were 8,
483 surgeries during this study period: 3, 168 (37%) HMO, with an overall
operative mortality of 2.7%, and 5, 315 (63%) non-HMO, with an operative
mortality of 4.6% (P=.00002). All patients were operated on in the same
hospital by the same surgical group.
We investigated
this difference with univariate and multivariable analyses. 19 risk factors
were found to univariately affect the risk of operative mortality (p<.05).
For 11 of these risk factors there was a significant maldistribution between
HMO and non-HMO patients; HMO patients had worse average values for 3 factors
and better values for 8 (the latter included age, previous CBS, abnormal wall
motion, chronic angina, and emergency surgery).
We used
logistic regression to explore the influence of this imbalance in risk factors.
The model found 7 factors to significantly affect operative mortality, after
which the variable indicating HMO membership was no longer significant
(p=.006). Because of missing data, only 1, 279 (40%) HMO patients and 2, 407
(45%) non-HMO patients, with operative mortalities of 2.6% and 4.1%,
respectively, could be used.
A reasonable
conclusion is that the difference in operative mortality between a coherent and
chaotic system of cardiologic management results in a distribution of risk
factors that enhance the operative results in the coherent group. The question
of whether this selection process would be beneficial to a large population at
risk has not been addressed.
*By invitation
42. REDUCING THE RISK OF INFECTIVE
ENDOCARDITIS AFTER AORTIC VALVE REPLACEMENT
Arvind K. Agnihotri, M.D.*, David
C. McGiffin, M.D.*, Andrew J. Galbraith, M.D.* and Mark F. O'Brien, M.D.
Birmingham, Alabama and
Brisbane, Australia
Replacement
valve endocarditis (RVE) occurred on 3.9% of 2, 686 aortic valve replacement
devices inserted between December 31, 1969 and January 1, 1992, based on a
cross-sectional follow-up in 1992 which was 98.8% complete. As shown by others,
the risk (hazard function) for RVE was highest early after valve replacement,
peaking 3 months after operation, then decreasing to reach a constant hazard by
about 6 months after operation. By multivariable analysis, patients with active
preoperative endocarditis (p<.0001) or those receiving a synthetic aortic
root replacement (p=.0006) were at an increased early risk for RVE, but this
increased risk was neutralized when an allograft valve was used (p<.0001;
figure A [figures A and B are nomograms of the multivariable equation]). Late
risk (later than 6 months after operation) was increased in younger patients
(p<.0001), those with renal failure (p=.01), and in patients with active or
remote preoperation endocarditis (p=.04). Late risk was particularly high in
patients with preoperative Staphylococcus aureus endocarditis (p=.05),
which tended to recur as another staphylococcal endocarditis. Use of some
mechanical valves resulted in a reduction in late risk (p=.05; figure B, while
use of some xenograft valves increased late risk (p=.02).
In patients without risk factors, valve replacement
with any modern device results in a similar infectious risk (figure C). In the
presence of early phase risk factors use of an allograft valve reduces the risk
of RVE. In patients with only late phase risk factors the use of some
mechanical valves may be preferable.
*By invitation
43. SURGICAL TREATMENT OF PROSTHETIC VALVE
ENDOCARDITIS
Bruce W. Lytle, M.D., Brian P.
Priest, M.D.*, Paul C. Taylor, M.D.*, Floyd D. Loop, M.D., Robert W. Stewart,
M.D.*, Patrick M. McCarthy, M.D.*, Derek Muehrcke, M.D.* and Delos M. Cosgrove,
M.D.
Cleveland,
Ohio
From 1975
through 1992, we reoperated on 146 patients for the treatment of prosthetic valve
endocarditis (PVE). Inclusion in the study stopped in 1992 to allow follow-up
of all patients. PVE was considered early (<1 year after operation) in 46
cases, active in 103 cases, and the extent of the infection was prosthesis
only, 66, annulus, 46, and cardiac invasion, 34. Surgical techniques evolved in
the direction of increasingly radical debridement and reconstruction with
biological materials. All patients were treated with prolonged postoperative
antibiotic therapy.
There were 19
(13%) in-hospital deaths. Univariate analyses demonstrated trends toward
increasing risk for patients with active PVE and extension of infection beyond
the prosthesis; however, the only variables with a significant (P<0.05)
association with increased in-hospital mortality confirmed with multivariate
testing were impaired LV function, heart block, major organ system failure and
identification of organisms in the pathology specimen. During the study period,
mortality decreased from 20% (1975-1984) to 10% (1984-1992). For hospital
survivors the mean length of stay was 25 days.
Follow-up (mean
interval 62 months) documented late survival of 82% at 5 and 60% at 10
postoperative years. Increasing age was the only factor associated (P=0.006)
with late mortality. Nineteen patients needed at least one further operation;
reoperation-free survival was 75% at 5 and 50% at 10 postoperative years. Fever
in the immediate preoperative period was the only factor associated with
decreased late reoperation-free survival (P=0.049).
PVE remains a
serious complication of valve replacement but the in-hospital mortality of
reoperations for PVE has declined. With extensive debridement of infected
tissue and postoperative antibiotic therapy the extent and activity of PVE does
not appear to have a major impact on late outcome and the majority of patients
with PVE survive for 10 years after surgery.
*By invitation
44. THE ADDITIONAL HOSPITAL COSTS
GENERATED IN THE MANAGEMENT OF COMPLICATIONS OF PACEMAKER AND DEFIBRILLATOR
IMPLANTATIONS
T. Bruce Ferguson, Jr., M.D.,
Candice Lilley Ferguson, M.S.P.H.* and Patricia Crimmins-Reda, R.N., M.S.N.*
St. Louis, Missouri
The rapid
approach of capitated reimbursement mandates that providers examine their
practice patterns associated with all surgical procedures. As part of this
effort, documentation of 1) the complications associated with these procedures;
and 2) the additional hospital costs associated with the management of
these complications, is critical for comprehensive fiscal accountability. This
study analyzed the fully-loaded hospital costs generated in the management of
the most common surgical complications - infection, lead-related problems and
hematoma formation requiring evacuation - associated with pacemaker and
non-thoracotomy implantable defibrillator therapies.
Between July
1989 and September 1994 a total of 1, 031 pacemaker (PM) and 331 implantable
defibrillator (ICD) procedures were performed by a cardiac surgeon in a
tertiary-level teaching hospital setting. Over the past two years, 105 of these
ICD procedures involved non-thoracotomy (NT-ICD) systems. Because of the
commonly presumed similarities between PM and NT-ICD procedures, these two
groups will be examined in this analysis.
There were no
deaths associated with the 1, 136 procedures. The overall in-house PM infection
rate was 0.58% (6/1, 031). An additional nine PM patients were transferred from
outside institutions for definitive therapy of infected systems. The in-house
PM lead reposition/replacement rate was 4.1% (37/902 procedures involving lead
placement), performed from 1-78 days post-initial implant. Four PM patients
developed pocket hematomas requiring evacuation; all were on systemic
anticoagulation for medical problems. The overall in-house infection rate for
NT-ICD was 0.95% (1/105). Two patients, both on systemic anticoagulation,
developed pocket hematomas requiring reexplora-tion; both required lead
configuration modifications due to elevated defibrilla-tion thresholds (DFTs)
at the second procedure. Two patients had ICD system malfunctions, and four
other patients (3.8%) had lead fractures (N=2) or dis-lodgements that
necessitated surgical reexploration.
The additional
fully-loaded hospital costs were documented as additional length of stay (LOS)
in-hospital, ICU requirement, OR procedure costs, device costs and additional
pharmacy, administrative and miscellaneous costs directly associated
with the complication (data are expressed as mean ± SD):
Procedure
|
Complication
|
#Pts
|
Mean Age
|
Mean LOS
|
Added Costs
|
|
|
|
|
(Yrs)
|
(Days)
|
($)
|
|
PM
|
Infection
|
15
|
63.4 ± 17.4
|
17.3 ± 7.0
|
30, 765 ± 12, 984
|
|
|
Lead-Related
|
37
|
65.1 ± 15.3
|
2.4 ± 1.8
|
4, 595 ± 1, 734
|
|
|
Hematoma
|
4
|
63.5 ± 16.5
|
5.0 ± 4.7
|
7, 596 ± 4, 998
|
|
NT-ICD
|
Infection
|
1
|
52
|
16
|
63, 830
|
|
|
Lead-Related
|
4
|
47.3 ± 17.6
|
3.5 ± 0.6
|
13, 056 ± 6, 091
|
|
|
Hematoma/High DFTs
|
2
|
46.5 ± 24.7
|
11.0 ± 4.2
|
30, 592 ± 8, 994
|
|
|
System Malfunction
|
2
|
69.5 ± 10.6
|
2.5 ± 2.1
|
7, 978 ± 5, 032
|
Thus management
of these common complications of PM and NT-ICD therapies is expensive. For all
Medicare patients with complications in this study, costs exceeded
reimbursement, suggesting that similar shortfalls would occur under a
capitation scheme. The study demonstrates that accurate identification of the
costs associated with complications of interventional procedures is feasible.
This information is critical to a complete understanding of the financial
impact of surgical procedures in a capitated reimbursement environment.
10:50 am INTERMISSION
*By invitation
11:10 am SIMULTANEOUS SCIENTIFIC SESSION D
ADULT CARDIAC SURGERY
Grand Ballroom, Sheraton Boston Hotel
Moderators: D. Glenn Pennington, M.D.
Robert L. Hardesty, M.D.
45. A PROSPECTIVE RANDOMIZED TRIAL OF
EARLY EXTUBATION AFTER CORONARY ARTERY BYPASS
Charles M. Peniston, M.D., C.M.*,
Davy Cheng, M.D.*, Jacek Karski, M.D.*, Zhao Sun, M.A.*, Susan Armstrong,
M.Sc.* and
Tirone E. David, M.D.
Toronto, Ontario, Canada
Early
extubation within the first few hours after cardiac surgery has been proposed
as a safe method of cost containment by reducing ICU-and hospital stay. Early
extubation has been possible in most cardiac patients by modifying the
anaesthetic. All patients who had this modified anaesthetic were
retrospectively reviewed to determine the predictors of failure of early
extubation. Stepwise logistic regression analysis revealed that age > 65
years, female gender, moderate or severe left ventricular function and urgent
operations were associated with a lower probability of early extubation. We
then undertook a prospective study to determine if early extubation is safe and
reduces the length of ICU and hospital stay after coronary artery bypass (CAB).
Methods: After
institutional approval, 89 patients undergoing elective CAB were randomized to
either conventional anaesthesia (CONVENTIONAL) (induction with fentanyl 50
meg/kg; maintenance with isoflurane and midazo-lam 0.1 mg/kg/hr) and assisted
ventilation until next morning after surgery, or modified anaesthesia (EARLY
EXTUBATION) (induction with fentanyl 15 meg/kg, isoflurane and propafol 2-4
mg/kg/hr) and early extubation (1 to 6 hours post-op). Continuous ST analysis
was performed with pre-op baseline to 48 hrs postop. CK and CK-MB were measured
at 6, 12, 24, 36, and 48 hrs after X-clamp release. Arterial and venous blood
gases were measured at 240 mins after extubation. Respiratory patterns and
shunt fraction (Qs/Qt) were monitored for 24 hours after extubation. Unless
indicated data are expressed as mean ± S.D. and were compared by Student's
t-test.
RESULTS
|
CONVENTIONAL
|
EARLY EXTUBATION
|
|
Number of patients
|
45
|
44
|
|
Age
|
61 ± 11
|
58 ± 9
|
|
Number of grafts
|
3.2 ± 1.0
|
3.5 ± 1.0
|
|
Incidence of ST changes
|
39%
|
50%
|
|
Maximum CK-MB (IU/L)
|
25
|
18
|
|
Pulmonary shunt (Qs/Qt)
|
23 ± 9%
|
13 ± 6%*
|
|
Assisted ventilation (hrs)
|
18.9 ± 1.9
|
3.8 ± 1.1*
|
|
Apnea incidence
|
30%
|
22%
|
|
ICU discharge criteria (hrs)
|
25.6 ± 10.1
|
7.0 ± 1.8*
|
|
Hospital stay (days)
|
9.1 ± 3.8
|
6.9 ± 1.4*
|
|
*indicates p<0.05 between
groups
|
|
|
Data from 784 patients undergoing CAB or valve
procedures were also examined. ICU length of stay was reduced from 2.5±4.7 days
to 1.43±0.9 days (p<0.0001) and hospital stay was reduced from 10.6±7.5 days
to 8.3±4.2 days (p<0.0001).
Conclusion: These
results indicate that early extubation after elective CAB is safe and reduces
the length of ICU and hospital stay.
*By invitation
46. ANTI-ISCHEMIC AND ANTI-ARRHYTHMIC
PROTECTION BY PERIOPERATIVE INFUSION OF NIFEDIPINE AND ETOPROLOL IN PATIENTS
UNDERGOING ELECTIVE AORTOCORONARY BYPASS SURGERY
Bruno K. Podesser, M.D.*, Severin
S. Schwarzacher, M.D.*, Werner Zwolfer, M.D.*, Friedrich Peschl, M.D.*, Thomas
Binder, M.D.*, Ernst Wolner, M.D. and Rainald Seitelberger, M.D.*
Vienna, Austria
A randomised study was performed on 70 patients
undergoing elective coronary bypass procedure to examine whether the combined
perioperative 24-hour infusion of nifedipine (10 ug/kg/h) and metopropol (12
ug/kg/h) reduces the incidence of perioperative myocardial ischemia and
arrhythmias (group NM, n=34). The control group (group N, n=36) received
nifedipine only. Repeated assessments of serum enzyme levels (CK, CK-MB) and
12-lead-ECG together with a 3-channel Holier monitoring over 48h were used to
classify perioperative myocardial ischemia (transient ischemic event,
myocardial infarction) and supraventricular and ventricular arrhythmias.
The two groups
did not differ with respect to their demographic data, extracorporeal
circulation, aortic cross-clamping time, or number of distal anastomosis. No
perioperative myocardial infarction in either group was detected. However, a
significantly lower incidence of transient ischemic events was observed in the
NM group as compared to the N group (3% versus 11%; p<0.05). In addition,
there was a tendency towards lower CK-MB-levels and peak-values of CK- and
CK-MB-enzymes in the NM group. With regard to perioperative dysrhythmias, there
was a significantly lower incidence of sinus tachycardia (9%) and atrial
flutter/fibrillation (6%) in the NM group as compared to the N group (33% and
27%, p<0.05). In addition, postoperative heart rate was lower in the NM
group starting from the 6th hour after opening the aortic cross-clamp.
In conclusion,
the combined perioperative infusion of nifedipine and metoprolol is superior in
preventing perioperative myocardial ischemia and decreasing the incidence of
supraventricular arrhythmias as compared to a single-drug regimen with
nifedipine.
*By invitation
47. TRANSPLANT CANDIDATES' CLINICAL
STATUS RATHER THAN RIGHT VENTRICULAR FUNCTION DEFINES NEED FOR UNIVENTRICULAR
VS. BIVENTRICULAR SUPPORT
Robert L. Kormos, M.D, Si M.
Pham, M.D.*, Thomas A. Gasior, M.D.*, Srinivas Murali, M.D.*, Brack G. Rattier,
M.D., Ph.D.* and Hartley P. Griffith, M.D.
Pittsburgh, Pennsylvania
We have studied our experience since 1988 in 31
patients who required a mechanical circulatory bridge to transplantation who
also had biventricular failure (mean RV ejection fraction [RVEF] = 12%) to
better define the need for biventricular or total artificial heart support vs
univentricular support (LVAS). Clinical factors including preoperative
inotropic need, fever without detectable infection, radiographic diffuse
pulmonary edema, postoperative blood transfusion and RV thickness were compared
with hemodynamic parameters including cardiac index, RVEF, CVP, mean PAP, and
total pulmonary resistance for their ability to predict need for mechanical or
high dose inotropic support for the RV. Patients were grouped as to the need
for RV support following LVAS implantation: None (I)=14, inotropic drugs
(II)=7, and RV mechanical support (III)=10. There were no differences in
preimplant hemodynamic variables. Groups II and III had a significantly lower
mixed venous oxygen saturation (39.2% vs 52.4% in Group I; p<0.001), a
greater level of inotropic need (p<0.02), greater impairment of mental
status, and a lower ratio of RVEF to inotropic need (0.37 vs 0.56 for Group I;
p<0.02) before LVAS implantation. A significant discriminator between Groups
II and III was the presence of a fever without infection within 10 days of LVAS
implant (14% in Group II vs 80% in Group III). Group III had more patients with
preimplant pulmonary edema on chest radiograph and a greater requirement for
postoperative blood transfusion (6 units cells in Group II vs 38 in Group III).
RV thickness at LVAS explant was 0.87 cm in Group III vs. 44 cm in Group II
(p<0.05). Transplantation rates after bridging were 100% in Group I, 71 % in
Group II and 50% in Group III. Clinical factors which reflect preimplant degree
of illness and perioperative factors which result in impairment of pulmonary
blood flow or reduced perfusion of the right ventricle after LVAS implantation
are now felt to be more predictive of the need for additional RV support than
preimplant measures of RV function or hemodynamics.
12:10pm ADJOURN
*By invitation
9:30 am SIMULTANEOUS SCIENTIFIC SESSION
E
GENERAL THORACIC SURGERY
Republic Ballroom, Sheraton
Boston Hotel
Moderators: Victor F. Trastek, M.D.
Martin F. McKneally, M.D.
48. RESULTS AND PROGNOSTIC FACTORS IN
RESECTIONS OF PRIMARY TRACHEAL TUMORS
J.F. Regnard, M.D.*, P.
Fourquier, M.D.* and Ph.Levasseur, M.D.*
Paris, France
Sponsored by: Peter C.
Pairolero, M.D., Rochester Minnesota
From 1970 to
1993, 208 patients with primary tracheal tumors were evaluated in a
multicentric retrospective study including 26 centers. Ninety-four patients had
a squamous cell carcinoma of the trachea, 4 had adeno-carcinoma, 65 had adenoid
cystic carcinoma and 45 patients, miscellaneous tumors. The following
resections were performed: tracheal resection with primary anastomosis, 146;
partial tracheal resection, 19; carinal resection, 24; and tracheo-laryngeal
resection, 19. In average, the length of the resected specimen was 38.5 mm
(10-60). Postoperative complications occurred in 41% and postoperative
mortality was 10.5%. Postoperative morbidity and mortality were statistically
correlated (PO.05) to the length of the resection, to the need of a laryngeal
release, to the type of resection and to the histologic type. Follow-up was
complete for all but 10 patients with a mean follow-up of 5 years. Fifty-nine
percent of the patients with tracheal cancers and 43% of the patients with
adenoid cystic carcinomas had postoperative radiotherapy.
In complete
resection, the 5 and 10-year actuarial survival were respectively 55% and 30%
in tracheal cancers, 82% and 25% in adenoid cystic carcinomas. Long-term survival
was altered by the occurrence of second primary cancer (ORL, lung) in the group
of patients with tracheal cancers and by late metastases in adenoid cystic
carcinomas. Postoperative radiotherapy did not improve survival in the group of
patients with tracheal cancer when the resection was complete, even if nodes
were involved. However, in case of incomplete resection, postoperative
radiotherapy did not improve survival in the group of patients with tracheal
cancer when the resection was complete, even if nodes were involved. However,
in case of incomplete resection, postoperative radiotherapy improved survival
(P<0.02). For adenoid cystic carcinomas, the actuarial survival seemed
better in complete resection than in incomplete resection but the difference
was not statistically significant (PO.20). Postoperative radiotherapy did not
improve survival in adenoid cystic carcinoma, even in incomplete resection.
Surgery is the
treatment of choice of primary tracheal tumors.
*By invitation
49. THE IMPORTANCE OF SURGICAL STAGING IN
THE TREATMENT OF MALIGNANT PLEURAL MESOTHELIOMA
Valerie W. Rusch, M.D. and
Ennapadam Venkatraman, Ph.D.*
New York, New York
Progress in the
therapy of malignant pleural mesothelioma (MPM) is hindered by the lack of an
adequate staging system and controversy about prognostic factors. This personal
surgical series was analyzed to determine the value of a new TNM staging system
proposed by the International Mesothelioma Interest Group (IMIG), and to
examine factors that could affect the design of future clinical trials.
Methods:
Thoracotomy was done in previously untreated patients (pts) if CT scans
showed technically resectable tumor confined to one hemitnorax.
Pleurectomy/decortication (P/D) was used in pts with minimal visceral pleural
tumor, extrapleural pneumonectomy (EPP) in pts with more locally advanced
disease. Complete resection was defined as no gross residual tumor. Adjuvant
therapy was given as required by serial clinical trials. Pts were followed by
chest and abdomen CT scans every 3 months after death. Prognostic factors were
examined by log rank and Cox regression analyses.
Results:
From 10/83 to 7/94 there were 131 consecutive thoracotomies, 101
resections, 72 complete. EPP:P/D=50:51. Men:women=108:23. Median age=63
years (range=32-80). Operative mortality 5/131 pts (3.8%), 3/50 EPP (6%). Most
frequent morbidity: atrial arrhythmias, 14/131 pts (11%), 11/50 EPP (22%).
95/131 tumors were epithelial. 51/89 pts (57%) having node dissections had (+)
nodes, 45 (50%) N2.
|
Survival
|
Operation
|
T status
|
N status
|
Stage
|
Histology
|
|
|
EPP
|
P/D
|
Tl
|
T2
|
T3
|
T4
|
NO
|
Nl-3
|
I
|
II
|
III
|
Epi
|
Non-Epi
|
|
|
