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34.8
Complete recanalisation of a bilateral traumatic carotid artery dissection with high grade stenosis of
the right and complete occlusion of the left side
N. Meyer, B. Rodic, M. Rudin, A. Horst, Th. Hotz, K. Käch, P. Wigger (Winterthur)
Objective: Treatment of traumatic carotid artery dissection is controversial. We report a case of bilateral
dissection with complete occlusion on one side which completely recanalized.
Methods: A 25-year old male motorcyclist was admitted after a collision with a car. He broke the windscreen
by his helmet protected head. He presented with a Glasgow coma scale of 11, a blunt thoracoabdominal
trauma, a scrotal hematoma and a fracture of the distal left radius. A CT-angiography of
the neck and brain revealed a small sub-arachnoid-hemorrhage of the left hemisphere and a bilateral
internal carotid artery dissection. The patient was admitted to the intensive care unit and developped
no neurological symptoms. Duplex sonography showed complete occlusion of the left internal carotid
artery (ICA) and a 70% stenosis on the right ICA. The patient was heparinized and developed a scrotal
hematoma. Therefore the heparin dose was intermittently reduced for two days. The patient was discharged
on oral anticoagulation 16 days after admission.
Results: The patient had an asymptomatic course. After two months duplex scan showed a complete
recanalisation of both ICA’s and anticoagulation (Marcoumar) was replaced through antiplatelet treatment
(Aspirin 100mg). Three months after trauma a aneurysm (5x12mm) of the right ICA was diagnosed
by MRA which was decreasing in size during follow up resolved completely 17 months after
trauma. Antiplatelet treatment then was stopped.
Conclusion: Cervicocephalic artery dissections should be considered in patients after severe head or
neck trauma even if no clinical symptoms are present. There is a lack of consensus regarding treatment
modalities. Anticoagulants and antiplatelet drugs may prevent ischemic stroke, but bleeding
from traumatized tissues may offset the benefits of antithrombotic treatment as occured in our case.
A systematic review in over 700 patients showed no difference between the two treatment regimens.
The prognosis is excellent in cases limited to local signs and poor in about 15%. The incidence of
recurrent cerebral ischemic events in CAD is between 1 and 2%. Healing of arterial dissections occurs
within three to six months, with resolution of stenosis seen in 90%, and recanalization of occlusions in
approximately 50%. The choice of antiplatelets or anticoagulants remains a personal decision of the
treating physician.
34.9
Treatment of a extracranial carotid aneurysm complicating Behçet disease.
X. Berard 1 , S. Déglise 2 , F. Saucy 2 , A. Mennet 2 , C. Haller 2 , J.-M. Corpataux 2 ( 1 Bordeaux/FR, 2 Lausanne)
Objective: Extracranial carotid aneurysm is a rare vascular manifestation of Behçet disease (BD). To
our knowledge, only 20 cases have been reported in the literature.
Methods: This study presents a complex case of extracranial carotid aneurysm. Based on this experience
and a review of the literature, surgical options for carotid aneurysm in patients with BD are
discussed and evaluated.
Results: A 28-year-old West Indian man was admitted for a rapid expanding right extracranial carotid
aneurysm complicating BD. Primary treatment consisted of resection followed by interposition of a
saphenous vein graft. Twelve months after vein graft reconstruction, the patient developed a nonanastomotic
pseudo-aneurysm. Reoperation was performed with removal of the pseudo aneurysm
followed by reconstruction using a PTFE graft. Three months after reoperation, the patient presented
another pseudo-aneurysm between the remaining vein graft and PTFE graft. Endovascular treatment
was undertaken but the stent occluded before discharge. The patient remained asymptomatic and
was discharged without further treatment. Oral ulcerations were found prior to the first intervention and
both reoperations. Medical treatment consisted of aspirin 160 mg/d and colchicine 1mg/day prednisone
20mg/d aspirin, colchicine and prednisone after the first reparation, and aspirin, colchicine,
prednisone, and azathioprine after the second reoperation.
Conclusion: Analysis of the literature and our report have 4 main implications in the treatment of carotid
aneurysm in BD. First, synthetic grafts should be preferred to autogenous grafts. Second, endovascular
exclusion based on careful CT-scan vessel sizing appears to be a promising option but further study
is needed to assess long-term benefits. Third, ligature should be considered in case of intraoperative
difficulty. Fourth, regardless of surgical technique, post-operative innumosuppessive therapy is necessary
to control disease activity.
Thoracic Surgery 35
35.1
Photodynamic therapy enhances lipodoxorubcin distribution in sarcoma lung metastasis by lowering
tumor interstitial fluid pressure in a rodent model
J. Y. Perentes, C. Cheng, M. Gonzalez, Y. Wang, H.-B. Ris, T. Krueger (Lausanne)
Objective: The management of sarcoma metastasis by systemic chemotherapy is often unsatisfactory.
This has paradoxally been attributed to the leakiness of tumor neovessels which induce high intratumor
interstitial fluid pressure (IFP) and limit convection forces that are important for drug distribution.
In a rodent model, we have recently shown that photodynamic (PDT) pre treatment of lung metastasis
could enhance their uptake of chemotherapy. We hypothesized that PDT transiently decreases tumor
IFP which enhances convection and promotes drug distribution.
Methods: Sarcoma tumors were generated sub-pleurally in the lungs of 12 rats. Animals were randomized
at 10 days into i. no pre-treatment (control) and ii. low dose PDT pre-treatment (0.0625 mg/kg
28 swiss knife 2010; 7: special edition
Visudyne ® , 10J/cm 2 and 35 mW/cm 2 ) followed by intravenous Liposomal doxorubicin (liporubicin TM )
administration. Using the wick-in-needle technique, we determined tumor and normal tissue IFP before,
during and after PDT. In parallel, the uptake of liporubicin TM was determined by high performance liquid
chromatography in tumor and lung tissues.
Results: Tumor IFP was significantly higher than normal tissue IFP in all animals. PDT pre-treatment
did not affect normal tissue IFP but caused a significant decrease in tumor IFP (mean decrease by
2+/- 1mmHg) which lasted an average of 30 minutes before reaching baseline values. Tumor but not
normal lung tissue liporubicin TM uptake was significantly increased by 67% with PDT pre-treatment
when liporubicin was allowed to circulate for one hour.
Conclusion: Photodynamic therapy pre-treatment enhances liporubicin TM uptake in sarcoma lung metastasis
by transiently decreasing tumor IFP. These PDT conditions seem to specifically modulate tumor
neovessels but not normal lung vessels.
35.2
Prevention of primary graft dysfunction in lung transplantation by n-acetylcysteine after prolonged
cold ischemia
I. Inci, B. Erne, S. Arni, S. Hillinger, W. Jungraithmayr, B. Leskosek, W. Weder (Zurich)
Objective: Primary graft dysfunction continues to be a problem after lung transplantation resulting in
significant postoperative morbidity and mortality. This study assessed the protective effect of N-acetylcysteine
on primary graft dysfunction after lung transplantation.
Methods: Pig single left lung transplantation was performed in two experimental groups after 24
hours of cold (4°C) ischemia. Donor and recipient animals were treated with intravenous injection
of 150 mg/kg N-acetylcysteine (NAC) 60 minutes prior to harvest and reperfusion, followed by 12.5
mg/kg/hour continuous perfusion during the 8 hour observation period (NAC group). In the control
group (CON) animals did not receive any treatment. Hemodynamic and respiratory parameters were
recorded throughout the observation period. Bronchoalveolar lavage (BAL) nitrite/nitrate, neutrophil
elastase (NE), protein, IL-8 and lung tissue and red blood cell reduced glutathione (GSH) and NFK-B
(p50) levels were measured.
Results: During the observation period the mean pulmonary artery pressure, oxygenation, airway pressure,
and static lung compliance were significantly better in NAC compared to CON group. Extravascular
lung water index was higher at all time points during the reperfusion in the CON group. BAL protein,
nitrite/nitrate, NE, IL-8 levels at the end of the experiment were significantly higher in the CON compared
to NAC group. Lung tissue reduced glutathione (GSH) levels were significantly higher in NAC compared
to CON group. Red blood cell GSH levels were always higher in the NAC group during the reperfusion
period compared to CON group. Quantitative rt-PCR for IL-8 was significantly higher in CON during the
reperfusion period compared to NAC group (p=0.001). The amount of lung tissue NFK-B (p50) was
significantly higher in CON compared to NAC (p=0.03).
Conclusion: In this model, donor and recipient treatment with N-acetylcysteine effectively protected the
lung from primary graft dysfunction after prolonged cold ischemia.
35.3
Inhibition of tissue transglutaminase by inhibition of tissue transglutaminase sensitizes TRAIL-resistant
lung cancer cells through upregulation of death receptor 5
S. Frese 1 , M. Frese-Schaper 1 , J. Schardt 1 , T. Sakai 2 , R. A. Schmid 1 ( 1 Berne, 2 Kyoto/JP)
Objective: Tissue transglutaminase (TG2) is a member of the transglutaminase family of proteins that
is implicated to play a role in different cellular processes such as apoptosis, cell migration and cell
growth, angiogenesis, and matrix assembly. Its acyl transferase activity cross-links certain proteins,
among them transcription factors were described. Recent studies have demonstrated that cancer cell
lines which are apoptosis resistant express elevated levels of TG2 and can be sensitized to chemotherapy-induced
apoptosis by downregulation of this enzyme.
Methods: Experiments were performed using TRAIL-resistant lung cancer cell lines. Apoptosis was determined
by staining with propidium iodide and by measurement of caspase activity. Receptor expression
was determined by flow cytometry and quantitative RT-PCR. Promoter activity was measured by
transfection of cells with lucifearse-reporter plasmids.
Results: In the present study we show that the highly specific and irreversible acting small molecule
TG2-inhibitor KCC009 as well as downregulation of TG2 by small interference RNA reversed resistance
to tumor necrosis factor-related apoptosis-inducing factor (TRAIL) in lung cancer cells. Apoptosis
induced by the combination of KCC009 and TRAIL was accompanied by activation of caspase-3 and
-9. As a proposed mechanism, KCC009 increased mRNA and cell surface expression of death receptor
5 (DR5) while inhibition of DR5 upregulation abrogated the effect of KCC009 on TRAIL-induced
apoptosis. Using luciferase-reporter plasmids of the DR5 promoter region we further demonstrated
that KCC009-mediated upregulation of DR5 required the first intron of the DR5 gene. Although binding
sites for p53 and NF-kappaB are located in the first intronic region, KCC009-induced upregulation of
DR5 was independent from these transcription factors.
Conclusion: Inhibition of tissue transglutaminase provides an interesting strategy for the sensitization
to TRAIL-induced apoptosis. The combination of TRAIL and TG2 inhibitors therewith might present a
new option for the treatment of lung cancer.
35.4
Lung resection in hematologic patients with invasive pulmonary aspergillosis
C. Nebiker, D. Lardinois, L. Junker, F. Gambazzi, P. Matt, A. Gratwohl, D. Heim, L. Bubendorf, M. Tamm
(Basel)
Objective: Invasive pulmonary aspergillosis (IPA) is a frequent complication in patients with hematologic
malignancies undergoing high dose chemotherapy and autologous or allogenic stem cell trans-