TUESDAY MORNING, MAY 8, 1990
7:30 a.m. FORUM SESSION - Sheraton Ballroom
F1. CO2 Laser-Assisted Anastomoses in
Internal Mammary to Coronary Artery Bypass Grafts in Growing Piglets: A Five
Months Follow-Up
SEISUKE NAKATA*, PETER E. BLUNDELL,
CHARLES D. CAMPBELL and ROBERT L. REPLOGLE
Tokyo, Japan; Montreal, Quebec, Canada and Chicago,
Illinois
This study was designed to
evaluate the long-term complications and growth capabilities of laser-assisted
internal mammary to coronary artery (IM-C) bypass anastomosis in growing
piglets. Eight Yorkshire piglets weighing an average of 15 Kg. underwent IM-C
bypass operation using ex-tracorporeal circulation. In one-half the animals
(Group I) IM-C anastomosis was performed using a CO2 laser (65 mW,
Tohoku Ricoh, TC 3C 100) to weld tissues between 4 polypropylene stay sutures.
The laser technique will be demonstrated by videotape. The remaining animals
(Group II) had conventional anastomoses using 7-0 polypropylene. Animals were
sacrificed when their body weights reached 60 Kg. (average 5 months) and the
anastomoses were examined angiographically and microscopically for patency,
diameter, internal surface and aneurysm formation. Flow through the internal
mammary artery was measured using an electro-magnetic flow meter at the time of
surgery and just prior to sacrifice.
Results: In both Groups I and II the five month patency in
growing animals was 100%, but in Group II, 2 out of 4 anastomoses were almost
occluded by intimal hyperplasia. Aneurysm formation was not seen in either
group. Diameter of the anastomotic site in Group I animals grew 1.8 to 2.8 ±
0.3 mm. whereas in Group II it decreased from 1.8 to 1.4 ± 0.4 mm.
(p<0.05, Group I vs II). The calibre of the normal coronary arteries
increased from 1.8 to 3.0 mm. in diameter (normal growth). In Group I the flow
through the internal mammary artery increased from 30 to 120 ml/min while in
Group II the increase was from 30 to 70 ml/min.
Conclusions: Laser-assisted IM-C bypass anastomoses showed no
long-term complications and are superior in terms of growth potential and
lessened intimal hyperplasia to conventional suturing techniques. This
technique may have a useful application in patients with small coronary
arteries and in pediatric coronary artery surgery.
*By
Invitation
F2. Pericardial Influence on Internal
Defibrillation Energy Requirements
JOHN H. LEMMER, JR.*, LUKE A. FABER*,
D. JAMES MARIANO*, THOMAS A. DREWS* and
MICHAEL G. KIENZLE*
Iowa City, Iowa
Sponsored by: Douglas M. Behrendt, Iowa City, Iowa
There is no consensus
regarding optimal positioning of patch leads for automatic implantable
cardioverter-defibrillator (AICD) implantation. We compared energy (joules; J)
required for 50% and 80% successful defibrilla-tion (E50 and E80; probit
analysis) with titanium mesh patch leads (13.9 cm2) outside intact
normal pericardium and directly on the epicardium in 13 open chest dogs. Talc
was then instilled into the pericardial space to stimulate adhesion formation
and pericardial thickening (1-5 mm). After over 3 weeks of recovery,
thoracotomy and defibrillation testing were repeated with the patch leads
outside the thickened adherent pericardium. Results:
|
Patch Lead Location:
|
E50 (J):
|
E80 (J):
|
|
On
normal epicardium (n = 10)
|
9.6 ± 1.5
|
12.6 ± 1.7
|
|
Outside
normal pericardium (n = 13)
|
9.4 ± 1.3
|
13.0 ± 2.1
|
|
Outside
thickened pericardium (n = 9)
|
7.3 ± 0.9
|
9.8 ± 1.2
|
There were no significant
differences in defibrillation energy requirements between locations
(p>0.10). In addition, comparison of electrical impedence measurements at
10J were made. No significant differences in impedence at the different
locations were present (p>0.30).
We conclude that defibrillation energy
requirements are not altered by the presence of normal pericardium between the
patch leads and the heart as compared to being placed directly on the
epicardium in this animal model. Furthermore, thickened adherent pericardium
interposed between the patch leads and the heart does not increase
defibrillation energy requirements. These data suggest that placement of AICD
patch leads outside the pericardium in patients (including those with
pericardial adhesions from previous cardiac surgery) will not adversely affect
defibrillation efficacy and thus can simplify the implantation procedure.
*By
Invitation
F3. Deleterious Effects of High Initial
Reperfusion Pressures After Ischemia With Evidence for a Mechanism Involving
Endothelial Dysfunction
KAZUO SAWATARI*, TADASHI FUJIWARA *,
TERRY A. KURTTS*, WILLIAM D. ANDERSON* and
JOHN E. MAYER, JR.
Boston, Massachusetts; Tokyo, Japan; Birmingham,
Alabama
and Nashville, Tennessee
Conditions under which
myocardial blood flow is restored after ischemia (Isch) have an impact on
functional recovery, but the mechanisms involved in reperfusion (Rep) injury
remain incompletely defined. To assess the effect of intravascular pressure (P)
during Rep, isolated neonatal lamb hearts (n = 16) underwent 2 hrs of Isch with
K+ cardioplegia (15°C) with 8 reperfused at low P (20mmHg X 10 min,40mmHg X 10
min, then 60mmHg) and 8 at high P (60mmHg). Control hearts (n = 16) were cooled
(15°C) without Isch and rewarmed at low or high P. Recovery (Rec) of function
was assessed by measuring peak developed P (PDP) and end diastolic P (EDP)
during isovolumic contraction at an intra-ventricular balloon volume V'° which
caused an EDP of lOmmHg before Isch. In controls (no Isch), high vs. low P
during rewarming had no effect on PDP or EDP. High P post Isch resulted in 68%
Rec of PDP vs. 81% with low P (p<.01). EDP at V10 was higher
(p<.01) with high P (17.8mmHg) than low P (11mHg). Resting coronary blood
flow (CBF) was equal in high and low P groups pre-Isch, but post-Isch CBF was
75% of baseline with high P and 128% of baseline with low P (p<.05). To
explore the mechanism of the high P effect, 3 other groups (n = 24) had the
same 2 hr Isch insult. Endothelial function was assessed in 2 groups by the CBF
response to infusion of 10-6M acetylcholine (Ach) which causes
vasodilation, when endothelium (E) is intact, by release of E-derived
relaxation factor. Vascular smooth muscle responsiveness was assessed in a
third group with high Rep P by infusion of 5mcg/min nitroglycerine (TNG).
Before Isch, Ach caused 25% increase in CBF in both high and low P hearts.
Post-Isch, Ach caused 23% increase in CBF in low P hearts, but a 7% fall in CBF
in high P hearts (p<.005). TNG during Rep resulted in 134% Rec of CBF and
80% Rec of PDP despite high Rep P (p = ns vs low P). These results show that 1)
high Rep P after Isch reduces Rec of systolic and diastolic function, reduces
post-Isch CBF, and reduces E-dependent coronary vasodilation, 2) Rec of
mechanical function and CBF after high Rep P can be improved with the smooth
muscle relaxant TNG, and 3) endothelial dysfunction with loss of regulation of
coronary smooth muscle tone may be an important mechanism in the mechanical
dysfunction associated with high Rep P.
*By Invitation
F4. Reduction of Infarct Size by Systemic Amino
Acid Supplementation During Reperfusion
RICHARD M. ENGELMAN, JOHN A. ROUSOU,
JOSEPH E. FLACK*, JAISHIMA IYENGAR*,
YUTAKA KIMURA * and DIPAK K. DAS*
Springfield, Massachusetts and Farmington,
Connecticut
The amino acids, aspartate
and glutamate, in combination were evaluated as a means of reducing infarct
size and improving cardiac function during reperfusion in an intact pig
suffering an acute antero-septal infarct. Three groups of 6 pigs each were
randomly studied, control (no amino acids), 3 mM and 13 mM aspartate/glutamate.
The LAD coronary artery was occluded distal to its first diagonal branch for 60
minutes followed by 6 hour reperfusion. Aspartate/glutamate were administered
systemically immediately prior to reperfusion. The following parameters were
measured: infarct size and % area at risk, global metabolic function (coronary
blood flow, cardiac output and 02 consumption), global and regional
myocardial function, and tissue parameters of metabolic function (high energy
phosphate, acetyl CoA and long chain acyl CoA).
The results clearly showed
a significant decrease in infarct size from 61% of the area at risk in control
pigs to 37% in both 3 mm and 13 mm amino acid (AA) groups. Cardiac output and
coronary blood flow were not affected by the use of AA relative to the control
group. Only global 02 consumption was significantly decreased in
control pigs during reperfusion. Global LV mechanical function was not
adversely affected by the infarct and was not altered by AA administration.
Regional function, however, was significantly decreased by LAD occlusion in all
groups to near 20% and only significantly recovered to 64% in the 13 mm AA
group while remaining depressed at 22% in the control and 3 mm AA groups. High
energy phosphate and acetyl CoA measurements documented significant increases
in the AA groups relative to control and progressively greater levels with 13
than with 3 mm AA. Long chain acyl CoA was unchanged between the three groups.
The conclusions of this
study strongly support aspartate/glutamate supplementation for stunned,
reperfused myocardium. It is apparent that the effect of AA supplementation on
glycolysis is directly tranlated into improved regional function and reduced
infarct size.
*By
Invitation
F5. Donor Hearts With Impaired Hemodynamics:
Benefit of Warm Substrate Enriched Blood Cardioplegia Induction During Cardiac
Harvesting
DENIS B. TIXIER*, GEORG F. MATHEIS*,
GERALD D. BUCKBERG and HELEN H. YOUNG*
Los Angeles, California
Brain dead donors
frequently show circulatory deterioration, and often require so much inotropic
support that the donor heart is of questionable value. This experimental study
quantifies the cardiac metabolic consequences of brain death, and the role of
warm blood cardioplegic induction in improving the quality of potential donor
hearts with impaired hemodynamics.
Twelve dogs were subjected
to brain death by interrupting cerebral blood flow (ligation of innominate
artery, carotid arteries and superior vena cava) and followed for up to 6
hours. Each showed progressive hemodynamic deterioration, requiring inotropic
support (Dopamine, calcium, and Epinephrine) and large amounts of volume
replacement (Hespan) to suport the circulation (maintain mean arterial blood
pressure > 60 mmHg). Biopsies were taken after 6 hours or when irreversible
ventricular fibrillation occurred and analyzed for ATP, CP, glycogen, glutamate,
and lactate. In 6 dogs, the aorta was then clamped and a 10 minute infusion of
warm (37°C) substrate enriched aspartate/glutamate blood cardioplegia (using
the dog's own blood) was given by roller pump to simulate warm induction during
the harvesting process. Biopsies were then repeated.
Myocardial metabolism,
expressed as percent of control values, during brain death was characterized by
1) moderate energy depletion: ATP fell 25 ± 8%, CP fell 55 ± 15%*,2)
substrate depletion: tissue glutamate fell 48* ± 9.5%, glycogen fell 66* ± 7.5%,
and 3) evidence of anaerobic metabolism: lactate increased 374* ± 95%. Warm
induction of blood cardioplegia in these energy and substrate depleted ischemic
hearts showed, a) return of CP to normal (113 ± 16.8%), b) replenishment of
glutamate (201 ± 24% of control)*, and c) 43 ± 14% reduction in myocardial
lactate content.**
These data suggest that
brain dead donors requiring inotropic support sustain energy and substrate
depletion and ischemic damage that can be reversed by a brief period of warm
substrate enriched blood cardioplegic induction prior to harvesting. Warm
substrate enriched blood cardioplegia may increase the tolerance to subsequent
ischemia during organ storage, provide potential expansion of the donor pool,
and/or improve the potential function of hearts harvested from hemodynamically
impaired donors.
*p < 0.05 vs control:
mean ± standard error of the mean
**p < 0.05 vs brain
death animals
*By
Invitation
F6. Reduced Reperfusion Injury by Iron Chelation
in Canine Single Lung Transplantation
JOHN V. CONTE*, NEVINM. KATZ,
MARIE L. FOEGH*, JAMES ST. LOUIS*,
TINA WALSTROM*, PETER W. RAMWELL*
and ROBERT B. WALLACE
Washington, D.C.
Reperfusion injury impairs lung preservation
and is caused by the generation of oxygen derived free radicals. The generation
of hydroxyl radicals (- OH) via the Haber Weis reaction requires the presence
of free iron. We investigated the effect of a clinically used iron chelator,
deferoxamine (D), on reperfusion injury by measuring oxygen tension (pO2),
pulmonary vascular resistance (PVR), alveolar arterial oxygen difference (A-a),
and dynamic lung compliance (DLC) in two canine models of left single lung
transplantation.
Twelve dogs received
transplants following 22 hour preservation in modified Collins solution (MCS).
Lungs were inflated, flushed with preservation solution and stored at 10°C with
the bronchus, pulmonary artery (PA), and atrial cuff clamped. In six
experiments donor and recipient received 10mg/kg D prior to harvest, prior to
transplantation and in the preservation solution. Data were recorded following
thoracotomy, pneumonectomy, transplantation and for six hours following
ligation of non-transplanted PA. After 6 hours of ventilation with 100% 02 the
mean p02 was 175.1 ± 40 mmHg vs. 71.1 ± 23 for the controls (C) (p<0.001),
A-a was 502.3 ± 40 in the D group vs. 606. ± 24 mmHg for C (p<0.035). The
percent change in compliance during the reperfusion period was 26.9% for the D
group vs. 30.4% forC(p = NS)
Eight dogs received lungs
following 8 hours of storage in MCS. Four of these dogs received deferoxamine
as above. Dogs were immunosuppressed with azathioprine and cyclosporine and
data was recorded after 1 hour of reperfusion and from both the native and
transplanted lungs following inflation of PA occluders the day of surgery and
again on post op day 5. On post op day 5 with the dogs ventilated with 100% 02
mean p02 was 254.3 ± 35 mmHg for the D group and 89.9 ± for C (p<0.04) and
the A-a was 467 ± 73 dyne/sec/cm/ - 5 for C (p<0.02). Changes in compliance
were similar in both groups.
This data is important
because it shows that deferoxamine reduces reperfusion injury, and that the
effects are lasting. Unlike other free radical scavengers, D is not a protein
and not subject to the potential complications of parenteral protein
administration. Additionally because it blocks the hydroxyl radical, its
effects may be additive to other scavengers which block the superoxide radical.
*By Invitation
F7. Alterations
of Bronchoalveolar Lymphocyte Cytolytic Functions Following Lung Allograft
Rejection and Infection
HANI SHENNIB*, DAO M. NGUYEN*,
ISABELLE RAJOTTE* and DAVID S. MULDER
Montreal, Quebec, Canada
Differentiation of rejection from infection of
lung allografts remains difficult. We investigated the effects of these two
pathologic entities on the cytolytic activity of bronchoalveolar lavage (BAL)
lymphocytes. Left lung transplantation was performed on size-matched mongrel
dogs (n = 12). All animals received Cyclosporin A, Azathiopin, and Prednisone
for 2 weeks. Four recipients developed left lower lobe Gram negative pneumonia
within 10 days following transplantation. Remaining 8 dogs had their
immunosup-pression reduced and progressed gradually to severe rejection.
Cytolytic activity of left lung lymphocytes obtained by serial BAL's was
assessed by the lectin dependent cell mediated cytotoxicity (LDCMC) and natural
killer (NK) assays. Changes were correlated with histopathologic findings from
open lung biopsy.
|
|
Control
(Immunsup.)
|
|
Rejection
|
|
Infection
|
|
|
|
None
|
Early
|
Advanced
|
|
|
NK
|
2.3 ± 0.4
|
1.2 + 0.3
|
1.7 ± 0.5*
|
3.0 ± 0.7*
|
9.1 ± 1.1*
|
|
LDCMC
|
1.2 ± 0.2
|
2.8 ± 0.8
|
15.6 ± 2.2
|
44.5 ± 2.8*
|
14.6 ± 1.0*
|
(Mean
± SEM % lysis at 50:1 effector to target ratio, *p<0.001 Rejection vs.
Infection).
LDCMC activity
progressively and drastically increased as rejection advanced. There was no
detectable NK activity in rejecting allografts. Peripheral blood lymphocytes
however, in contrast to BAL lymphocytes, shared an increase in NK and LDCMC
activity in both settings of rejection and infection. We conclude that lung
allograft rejection and infection resulted in completely different alterations
of BAL lymphocyte cytolytic activity. Brochoalveolar lavage and functional
studies of lung lymphocytes, in contrast to blood lymphocytes, may be a useful
method in distinguishing allograft rejection from infection.
*By
Invitation
F8. In Vitro, In Vivo Phototherapy of Transfected
Human Lung Cancer
HARVEY I. PASS*, STEVEN EVANS*,
WILBERTA. MATTHEWS*, ROGER PERRY*,
JACK A. ROTH and PA UL SMITH*
Bethesda, Maryland and Houston, Texas
Photodynamic therapy (PDT)
with dihematoporphyrin ether (P-II) sensitizes malignant cells to damage by 630
nM light. The in vitro, in vivo PDT sensitivity of a transfected human
lung carcinoma line (45-342) was studied to establish a new PDT model. Using
the colony formation assay neither light alone nor P-II alone affected 45-342
cell survival. Energy-dependent PDT effects were seen in vitro in
P-II-incubated light exposed cells (90% cytotox-icity = 950 J/m2,
99% cytotoxicity = 1575 J/m2, p2 < .05), and cellular
[P-II] increased to a maximum of 2.77 ug/106 cells at 4 hours.
Ideal route (IV vs IP) of
P-II administration (10 mg/kg), tissue distribution kinetics, and PDT effects
were investigated in 133 nu/nu mice allografted subcutaneously with 45-342. IV
P-II was superior to IP P-II 24 hours after injection (32.4 ± 2.1 ug P-II/g dry
wt vs 17.7 ± 1.9 ug P-II/g dry wt, p2 < .01), and was more
precise (coefficient of variation p2 < .035). Tumor retained high
P-II levels (ug/dry wt), as seen below.
LEVELS
OF P-II vs TIME (HRS) POST INJECTION
|
|
TIME
|
|
Tissue
|
2
|
6
|
12
|
24
|
48
|
|
Tumor
|
29.7 ± 2.3*#
|
33.6 ± 2.6*#
|
30.3 ± 3.1*#
|
30.1 ± 3.2*#
|
18.8 ± 1.2*
|
|
Skin
|
13.5 ± 1.5
|
10.6 ± 0.9
|
9.6 ± 0.8
|
9.6 ± 0.7
|
9.6 ± 0.9
|
|
Muscle
|
5.9 ± 0.6
|
5.5 ± 0.5
|
6.3 ± 0.7
|
4.4 ± 0.3
|
4.7 ± 0.4
|
(*p2<.05
from skin and muscle, #p2<.001 from tumor at 48 hours)
Tumor/tissue ratios were
significantly elevated at 24 hours (tumor/skin = 3.0, tumor/muscle = 6.23)
compared to 48 hours (tumor/skin = 1.8, tumor/muscle = 3.8) [p2<.005].
PDT (.3W/cm2, 150J/cm2) 24 hours after IV P-II
administration caused progressive coagulative tumor necrosis (n = 16) and tumor
regression.
These data establish the
PDT sensitivity of transfected human lung cancer in vitro and in
vivo. Consistent levels of tissue P-II can be determined after IV
administration, and preferential tumor P-II retention observed. This tumor
model may be useful to study in vitro mechanisms of PDT action and in
vivo PDT effects to insure maximum selective tumor kill.
*By Invitation
F9. Cardiac 5'Nucleotidase Increases With Age and
Inversely Correlates With Recovery from Ischemia
MICHAEL A. GROSSO*, ANIRBAN BANERJEE*,
JOHN A. ST. CYR*, JAMES M. BROWN*,
GLENN J. WHITMAN*, DAVID N. CAMPBELL*,
DAVID R. CLARKE and ALDEN H. HARKEN
Denver, Colorado
The metabolic/biochemical basis for the
enhanced tolerance of immature hearts to ischemia remains to be elucidated.
Documented loss of high energy phosphate nucleotides occurs during
ischemia/reperfusion in mature hearts through the breakdown of ATP, ADP and AMP
(non-diffusable) to Adenosine (Ado) (freely diffusable). The enzyme responsible
for the conversion of AMP to Ado is 5'-Nucleotidase (5'NT). Previous work has
shown this nucleotide loss to be blunted in ischemic immature hearts. We
therefore hyothesized lower levels of this enzyme in immature versus mature
myocardium. The purposes of this study were (1) to document 5'NT activities in
immature and mature rabbit myocardium and (2) correlate differences of 5'NT
with functional recovery from ischemia. Neonatal (5-7 days) and adult (4-6
months) rabbit hearts were isolated and perfused (retrograde Langendorff). A
left ventricular balloon measured functional parameters. Hearts were subjected
to 10 min equilibration followed by freeze-clamping (5'NT assay) or 20 min
global 37° ischemia and reperfusion. Assay for
|
5'NT
utilized the linked formation
|
5'NUCLEOTIDASE
ACTIVITY
|
|
|
|
(nmoles/min/gm
tissue)
|
|
of
NAD at 340 nm:Arkesteijn
|
NEONATAL
|
3900
± 300
|
|
|
|
ADULT
|
13275
± 2060*
|
|
|
|
n
= 8 each group/*p < 0.05
|
|
VENTRICULAR
|
NEONATAL (n = 3)
|
|
|
FUNCTION
|
|
|
|
|
|
PREISCHEMIC
|
POSTISCHEMIC
|
%
|
|
DP
(mmHg)
|
53
± 1
|
53
± 6
|
104
|
|
LVEDP
(mmHg)
|
3
± 1
|
3
± 2
|
100
|
|
+
dp/dt (mmHg)
|
2800
± 116
|
2600
+ 231
|
99
|
|
sec
|
|
|
|
|
-
dp/dt (mmHg)
|
2900
+ 58
|
2933
± 475
|
102
|
|
sec
|
|
|
|
|
VENTRICULAR
|
5 ADULT (n = 4)
|
|
|
FUNCTION
|
|
|
|
|
|
PREISCHEMIC
|
POSTISCHEMIC
|
%
|
|
DP
(mmHg)
|
89
± 4
|
49
± 3*
|
56**
|
|
LVEDP
(mmHg)
|
5
± 1
|
10
± 3*
|
200**
|
|
+
dp/dt (mmHg)
|
3200
± 414
|
1900
± 238*
|
61
|
|
sec
|
|
|
|
|
-dp/dt
(mmHg)
|
2575
± 218
|
1650
± 183*
|
63**
|
|
sec
|
|
|
|
|
*p
< 0.01 post vs pre
|
**p<
0.01 adult vs neonatal
|
Functional recovery from ischemia inversely
correlated with age (r = 0.99) and 5'NT(r = 0.96)
We conclude: (1)
5'Nucleotidase levels are markedly diminished in neonatal versus adult
myocardium and (2) functional recovery following ischemia inversely correlates
with age and 5'-nucleotidase activity.
*By Invitation
F10. The Mechanism of Heart Failure Caused by
Cardiac Allograft Rejection
VERDI J. DiSESA *, PAOLO MASETTI*,
JAMES MARSH*, FREDERICK J. SHOEN* and
LAWRENCE H. COHN
Boston, Massachusetts
Rejection of the cardiac
allograft may cause reversible myocadial failure by a poorly defined mechanism.
To study this phenomenon, heterotopic cardiac transplantation was performed in
the Lewis rat using Lewis X Brown Norway (allografts) or Lewis (isografts)
donors. Without immunosuppres-sion, allografts are rejected in 6-8 days. At 3
days cardiac grafts were ex-planted and underwent functional measurements
(Langendorff apparatus) or pathologic and biochemical examination. Three-day
isografts (n = 9) had minimal histologic changes. Three-day allografts (n = 13)
showed rejection with lymphocytic infiltrate and myocyte necrosis. Functional
studies (n = 11) included heart rate (HR) (beats/min), cardiac output (CO)
(ml/min), coronary flow (CF) (ml/min), and stroke work (SW) (dynes/cm) at
baseline and in response to isoproterenol (3 x 10-8 M/ml):
|
|
HR
|
CO
|
CF
|
SW
|
|
Isografts
(n = 5)
|
213
|
27
|
8
|
7.9
|
|
Isoproterenol
|
353
|
45*
|
15
|
8.8*
|
|
Allografts
(n = 6)
|
237
|
22
|
7
|
6.0*
|
|
Isoproterenol
|
352
|
29*
|
14
|
5.4
|
|
|
|
*p < 0.05
|
|
|
Allograft ATP levels (n = 4) were normal (mean 41.9
nmol/mg).
Functional, biochemical, and pathological
studies in this small animal model demonstrate diminished contractile reserve
despite normal baseline function, chronotropic response, coronary flow and high
energy stores in allografts with early but significant rejection. These data
suggest that alteration in intra-cellular signals important in
excitation-contraction coupling are the mechanism of heart failure caused by
allograft rejection.
*By
Invitation
9:00 a.m. SCIENTIFIC SESSION - Sheraton
Ballroom
15. The Role of Extrapleural Pneumonectomy in
Malignant Pleural Mesothelioma
VALERIE W. RUSCH*, STEVEN PIANTODOSI*,
E. CARMACK HOLMES and THE LUNG CANCER
STUDY GROUP
New York, New York; Baltimore, Maryland and Los
Angeles, California
Malignant pleural
mesothelioma (MPM) is usually a fatal cancer for which surgery has been the
mainstay of treatment because chemotherapy and radiation are relatively
ineffective in this disease. The choice of operation for MPM remains
controversial. Extrapleural pneumonectomy (EPP) has been advocated because it
allows complete removal of gross tumor and can be associated with long-term
survival.
To evaluate EPP, we carried
out a prospective multi-institutional trial in patients with biopsy-proven
previously untreated MPM. Criteria for EPP were: (1) potentially completely
resectable unilateral disease by CT scan (2) predicted post-resection FEV1 >
IL/sec (3) no major medical problems. Patients who were not candidates for EPP
underwent pleurectomy/decortica-tion (P/D) or had non-surgical treatment (NST).
Results: from 9/85 to 6/88,
83 patients (64 males, 19 females) were entered.
|
|
#patients (% total)
|
mean age (yrs)
|
postop (%) deaths
|
recurrence rate (per
person yr)
|
death rate (per person
yr)
|
|
EPP
|
20 (24%)
|
56.7
|
3/20 (15)
|
0.616 p = 0.03
|
0.545 p>0.05
|
|
P/D
|
26(31%)
|
61.5
|
3/26 (11)
|
1.48
|
0.757
|
|
NST
|
37 (45%)
|
61.1
|
-
|
1.63
|
0.807
|
In univariate analyses,
epithelial versus sarcomatoid and mixed histologies had a better overall
survival (p = 0.02); and performance status (Karnofsky < 9) was predictive
of recurrence (p = 0.02). In multivariate analysis, histology, sex, age, EPP,
and performance status all had no significant impact on survival. EPP was
associated with a higher incidence of relapse in distant sites (7/20, 35%),
than were P/D (3/26, 11.5%) and NST (2/37, 5.4%).
Conclusions: (1) only a
small proportion of all MPM patients are candidates for EPP; (2) EPP carries a
significant operative mortality and does not improve overall survival compared
to more conservative forms of treatment; (3) EPP alters the patterns of
relapse; (4) factors previously thought to have an impact on survival in other
series did not affect outcome in this trial.
*By Invitation
16. Extrapleural Pneumonectomy, CAP Chemotherapy
and Radiotherapy in the Treatment of Diffuse Malignant Pleural Mesothelioma
DAVID J. SUGARBAKER*, THOMAS LEE*,
KAREN ANTMAN*, GREGOR Y COUPER *,
STEVEN MENTZER*, JOSEPHM. CORSON*,
JOHN J. COLLINS, JR., RICHARD SHEMIN
and ROBER T PUGATCH*
Boston, Massachusetts
Diffuse malignant
mesothelioma has been deemed a non-operative disease in many centers.
Extrapleural pneumonectomy has proven disappointing as have single and multiple
drug chemotherapy with or without radiotherapy in the treatment of diffuse
malignant mesothelioma. Median survivals of 10 to 15 months have been reported
with two year survival rates of 10-35%.
From 1980 to 1989, 30 patients with
pre-operative Stage I pleural mesothelioma (tumor confined within the capsule
of the parietal pleural, i.e. involving only the ipsilateral lung, pericardium,
and diaphragm) underwent extrapleural pneumonectomy with resection of
pericardium and diaphragm followed by three cycles of standard CAP chemotherapy
and 4500 rads of radiotherapy to the ipsilateral chest. All patients had the
pathologic diagnosis reviewed prior to treatment. The age of patients was 52.4
+/- 8.0 years (range 41-68 years); 25 were men and five women.
There were two post
operative deaths, (6%). One death was due to myocardial infarction defined at
autopsy and the other death was clinically attributed to pulmonary embolus.
For the 28 patients
surviving the operation, survival rates were 78% at one year, 52%at two
years, and 32% at three years. Sixteen patients are currently alive following
this trimodality therapy (median follow up 15.6 months) with one patient alive
at 56 months post treatment. The 12 patients who died of disease had a median
survival of 13.9 +/- 11 months.
These data suggest that radical
extrapleural pneumonectomy can be performed with an acceptable operative
mortality. When combined with post operative CAP chemotherapy and radiotherapy,
it may provide an effective therapeutic and palliative alternative in the
primary treatment of diffuse malignant mesothelioma.
*By
Invitation
17. Carinal Resection for Lung Cancer
DOUGLAS J. MATHISEN and HERMES C. GRILLO
Boston, Massachusetts
The revised staging system for lung cancer
classifies tumors within 2 centimeters of the carina as STAGE III B. This has
implied inoperability and incurability based on technical limitations rather
than advanced disease. Advances in bronchoplastic technique now allow resection
of the carina with lower morbidity and mortality and possible cure.
Consideration should be given to include this select group of patients in STAGE
III A.
We have treated 30 patients
with cancer of the lung requiring carinal resection. There were 24 males and 6
females. Histology was squamous cancer in 22 and adenocarcinoma in 7 and adenosquamous
carcinoma in 1. Right thoracotomy was used in all patients. Right carinal
pneumonectomy was performed in 15, resection of the carina plus the right upper
lobe with preservation of the right middle and lower lobes in 7, resection of
the carina alone in 6, and resection of the carina plus stump of bronchus
following prior pneumonectomy in 2 all with appropriate reconstructions. Eleven
patients had positive nodes. The majority of patients had postoperative
radiation therapy. There were 4 postoperative deaths (anastomotic
complications-1, pneumonia-2, ARDS-1). Two patients died 3 months
postoperatively from anastomotic complications. Excluding the operative deaths,
major complications included anastomotic stenosis requiring completion
pneumonectomy-1, anastomotic leak requiring omental wrap-1, pneumonia-4,
hoarseness-2. Of the operative survivors, there are 4 absolute 5 year
survivors, 5 patients are alive between 3 and 5 years, 12 alive between 1 and 3
years and 3 dead from disease 1 to 3½ years.
In selected patients,
carinal resection can be accomplished. The prospect for long-term survival now
appreciably exceeds the operative mortality and justifies this aggressive
approach.
INTERMISSION - VISIT EXHIBITS
*By
Invitation
10:45 a.m. SCIENTIFIC SESSIONS
18. Esophageal Ultrasound and the Preoperative
Staging of Carcinoma of the Esophagus
THOMAS W. RICE*, MICHAEL V. SIVAK*
and GREG A. BOYCE*
Cleveland, Ohio
Sponsored by: Floyd D. Loop, Cleveland, Ohio
Esophageal ultrasound [EUS]
allows the esophagus and paraesophageal tissue to be viewed as five discrete
layers. Lymph nodes are easily identified and their size, shape, margin, and
internal structure can be assessed. This provides an alternative method of
preoperative evaluation of the primary tumor status [T] and the regional lymph
node status [N] of patients with carcinoma of the esophagus.
EUS was attempted in the
preoperative staging of 28 patients with carcinoma of the esophagus. Six
patients were not assessed because of the inability to pass the esophageal
ultrasound probe through the malignant stricture. The AJCC staging system for
carcinoma of the esophagus was used.
Twenty-two patients had the
true T determined by pathologic review of the resected esophagus. EUS correctly
identified T in 13 patients (59% accuracy). Four patients were
overstaged by esophageal ultrasound; all these patients had early T, tumors
confined to the submucosa. Five patients were understaged by EUS; all of these
patients had advanced tumors (four T3 and one T4) that
invaded outside the esophageal wall. Seven of the nine incorrect EUS
determinations were called T2 (three T,, three T3, one T4)
suggesting that the borders of the muscularis propria may require careful
attention when evaluated by EUS.
Twenty patients had the
true N determined by pathologic review of the resected specimen. EUS correctly
identified N in 14 patients (70% accuracy). Three patients were falsely
identified as N, and three patients were falsely identified as N0.
The sensitivity, specificity, positive predictive value, and negative
predictive value for EUS and N assessment were 70%.
EUS provides an alternative
method of visualization of the esophageal wall and regional lymph nodes. Our
early experience shows promise for EUS in the preoperative staging of carcinoma
of the esophagus.
*By
Invitation
19. An Endothoracic Endoesophageal Pull-Through
Operation for Cancer of the Esophagus: Technique and Results in 68 Patients
FARROKH SAIDI*
Tehran, Iran
Sponsored by: Clement A. Hiebert, Portland, Maine
Transhiatal esophagectomy for cancer of the
distal or proximal esophagus is simplified if the uninvolved muscular layer of
the esophagus is left in situ. Mucosa of the normal segment is merely stripped
and removed as part of the specimen. A distensible muscle tunnel remains and
through it mobilized stomach or colon can be drawn to the neck. The approach is
based on three anatomic features of the normal esophagus: The mucosal layer is
tough, its attachment to the underlying muscle is flimsy, and vascular
connections are small.
The endothoracic
endoesophageal pull-through operation has been used in the palliative treatment
of 42 consecutive unselected patients with cancer of the lower esophagus or
cardia and three patients with cancer of the cervical esophagus. As with conventional
transhiatal esophagectomy, the chest is not opened. Following standard
mobilization of the stomach and resection of the tumor and regional lymph
nodes, the upper and lower thoracic ends of the normal esophagus are
circumcised and the mucosal layer cored out by finger dissection. Blood loss is
scant.
In 28 patients the stomach,
and in fourteen patients an isoperistaltic loop of colon was used for
reconstruction. The overall mortality was 13%, cervical anastomotic leakage
rate 13%, and survival rates at two and three years, respectively, 18% and 13%.
In a separate group of 26
patients, who required thoracotomy for middle 3rd cancer, mucosal stripping was
started 10 cm above the proximal tumor edge; the mobilized stomach was then
passed through this shorter muscular tunnel to allow a cervical anastomosis.
11:15 a.m. ADDRESS BY HONORED SPEAKER
"PIONEERS AND MILESTONES IN
THORACIC SURGERY"
A.P. Naef, Fully, Switzerland
12:00 p.m. ADJOURN FOR LUNCH - VISIT EXHIBITS
12:00 p.m. CARDIOTHORACIC RESIDENTS' LUNCHEON
Civic Ballroom (2nd floor)