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Background: Locally advanced (T4) non-small cell lung cancer (NSCLC) is principally amenable to surgery. For radical resection of cardiovascular structures, extracorporeal circulation (ECC) may be required. Tumor dissemination is a concern in this situation. In this study, we evaluate the long-term results of T4 NSCLC surgery with ECC and compare them with combined cardiopulmonary surgery for early-stage NSCLC and heart disease., Methods: We retrospectively analyzed 16 patients undergoing surgery on ECC over a 13-year period. Eight patients suffered from T4 NSCLC (group A), and another eight patients suffered from coincidental T1-T2 NSCLC and heart disease (group B)., Results: In group A, five patients received neoadjuvant radiochemotherapy. Complete resection was achieved in all patients. Thirty-day mortality was one patient (12.5%) in each group. Six patients died from recurrent cancer with a median survival of 13.6 months in group A. Prognosis in patients with direct tumor invasion of the aortopulmonary window was a lot worse compared to those with atrial infiltration. One T4 patient who had only received surgery survived for 155 months without relapse. In group B, no NSCLC relapse occurred, and median survival was 21.6 months. All but one death in group B occurred due to cardiovascular incidents., Conclusions: Surgery on ECC for T4 NSCLC gives satisfactory results. The site of infiltration appears to be most important for local tumor relapse. Long-term survival is possible in some cases. Simultaneous cardiac and pulmonary surgery resulted in good early and midterm outcomes without surgery-induced tumor propagation., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: Cardiopulmonary bypass (CPB) results in a systemic inflammatory response. Leukocytes play a crucial role in inflammatory reactions. Their gene expression profile in the context of CPB is unknown., Methods and Results: In a prospective, randomized, and double-blind clinical trial, 12 male patients underwent elective coronary artery bypass grafting with either heparin-coated (group H) or protein-coated (group P) CPB circuits. Oligonucleotide microarray analyses of 22,283 genes were performed on circulating leukocytes, collected immediately before surgery and 6 hours after CPB. Microarray results were validated with real-time polymerase chain reaction. All patients had uneventful surgery, and no significant differences between groups were observed during the clinical course. Multiple statistical analyses with different methods were performed. Compared with preoperative expression at a threshold value of P<0.01, postoperative expression revealed 814 upregulated and 1187 downregulated genes in group H compared with 99 upregulated and 231 downregulated in group P (P<0.001). Fifty genes exhibited a >4-fold increase and 27 exhibited a >4-fold decrease in group H, whereas only 7 genes exhibited upregulation and 7 revealed downregulation in group P. Microarray-pathway-profile-finder analyses determined 1405 upregulated and 1454 downregulated pathways in group H compared with 552 upregulated and 818 downregulated pathways in group P (P<0.01). Pathways related to inflammatory response exhibited highest z scores in group H, reflecting cellular inflammatory activation., Conclusions: Heparin coating resulted in a more profound alteration in leukocyte gene expression when compared with protein coating. Microarray analyses present an innovative approach for the evaluation and understanding of inflammatory reactions associated with CPB.

An inflammatory response to cardiopulmonary bypass (CPB) caused by bioincompatibility of extracorporeal circuits is one of the major clinical issues in cardiac surgery. Recently a new coating material, poly-2-methoxyethylacrylate (PMEA), was developed to improve the biocompatibility of blood contacting surfaces. In a simulated cardiopulmonary bypass model, using fresh human whole blood, 15 membrane oxygenators (Capiox SX18, Terumo Corp., Tokyo, Japan) were compared. Five of them had the PMEA coating, five had a heparin-coated surface, and five had no surface treatment. Blood samples were taken at several time-points during a 90 minute circulation period. Changes in coagulation, complement, and blood cell alteration factors were measured by ELISA methods, plasma bradykinin levels were measured by radioimmunoassay, and expression of genes encoding cytokines TNF-alpha, interleukin-1beta, interleukin-6, and interleukin-8 was determined by semiquantitative real time RT-PCR. Platelet adhesion was significantly reduced in both the PMEA and the heparin coated circuits. Release of platelet activation marker beta-thromboglobulin was significantly higher in the uncoated control group (p < 0.01). After 5 minutes of blood circulation bradykinin levels significantly increased in all three groups (p < 0.01); however, the group with the PMEA coated oxygenators showed the lowest values. Expression of genes encoding proinflammatory cytokines in monocytes was increased in all groups, with the lowest being in the PMEA coated group. PMEA coated CPB surfaces in an in vitro experimental model showed an improved thrombogenicity, reduced bradykinin release, less platelet activation and less proinflammatory cytokines gene expression in comparison with a noncoated group. The authors assume that PMEA coating may ameliorate some of intra- and postperfusion syndromes, particularly hypotension, unspecific inflammation, hyperfibrinolysis, and blood loss.

Cardiopulmonary bypass (CPB) surgery induces systemic release of proinflammatory cytokines causing unspecific inflammatory reactions. This study deals with the development of a sensitive technique for detecting changes at the mRNA level in monocytes of patients undergoing CPB surgery, by using real-time PCR. Blood samples from patients undergoing elective coronary artery bypass grafting were obtained at six different time points. RNA was extracted from isolated monocytes and cDNA was synthesized by reverse transcriptase. CPB surgery induced gene expression of IL-1beta, IL-6, IL-8, and TNF-alpha, followed by a decrease below the preoperative expression values 6 h post CPB. High significant increases in gene expression for IL-8 at the end of surgery (p = 0.001) were detected. Real-time PCR is a powerful tool for getting simultaneously numerous sensitive, accurate, and reliable results from small amounts of biological material. This method avoids time-consuming and hazardous post-PCR manipulations and decreases the potential risk of PCR contamination.

Background: Surgery of the aortic arch avoiding profound systemic hypothermia and using antegrade or retrograde cerebral perfusion has recently been popularized. This usually renders the CPB and surgical field set-up more complex. We propose a simple method achieving a similar effect., Methods: During a 6-month period, 7 patients (median age 72 years) underwent surgery involving the aortic arch with cannulation of the right subclavian artery for arterial return. There were 6 acute type A dissections and one ascending aorta and arch aneurysm. After commencing CPB, the ascending aorta was clamped and reconstruction of aortic valve and root were initiated. Patients were cooled to a tympanic temperature of 25 - 27 degrees C. CPB was then stopped, and the arch was opened and inspected from inside. While resuming arterial perfusion via the right subclavian artery, the arch branches were clamped sequentially from right to left under observation for back flow. Bilateral radial artery pressure and temporal transcutaneous oxygen saturation were always monitored., Results: In all cases, the aortic valve was spared using remodeling and resuspension techniques. 2 complete arch, 2 partial arch and 3 proximal arch replacements were performed. Mean times were 183 (113 - 321) minutes for CPB and 120 (67 - 213) minutes for aortic cross-clamping. Maximal systemic circulatory arrest time was 82 min. One patient died in the hospital due to MRSA sepsis with a normal CCT scan. All others were discharged in good condition., Conclusion: The initial experience with this simple technique of antegrade cerebral perfusion avoiding profound systemic hypothermia and the possible disadvantages of femoral artery cannulation appears promising.

Objective: Increased serum levels of a multitude of mediators like interleukins, tumor necrosis factor, elastase, adhesion molecules, and endotoxin have been described following cardiopulmonary bypass (CPB). The biological consequences of this complex response are unclear., Methods: Serum samples of nine patients scheduled for elective coronary artery bypass grafting were obtained preoperatively and 1, 6, and 12 h after weaning from CPB. Additional serum samples were obtained perioperatively from four patients undergoing major lung resection and from four healthy volunteers. The apoptosis-inducing activity of serum samples on endothelial cells was examined using a tissue culture assay system. Endothelial cells were derived from human umbilical cords and incubated for 48 h with serum samples in various dilutions during their second passage. The culture plates were fixed with methanol/acetone and stained with the DNA dye diamidinophenylindole. Apoptotic and normal cells were identified and counted using phase contrast and fluorescence microscopy., Results: The proportion of apoptotic endothelial cells was 5.6-fold higher in culture plates incubated with diluted (30%) serum samples obtained at 6 h after weaning from CPB when compared to plates incubated with preoperative samples (P=0.0077). A smaller effect occurred already at 1 h in some patients, whereas at 12 h after weaning from CPB no increased endothelial apoptosis was observed. No proapoptotic activity was found in preoperative as well as in control samples from patients undergoing lung resection or from healthy volunteers., Conclusions: Serum of patients after CPB exerts a strong apoptosis inducing activity on human endothelial cells. Apoptotic death of endothelial cells following CPB may be responsible for postoperative vascular and bypass dysfunction including phenomena like increased capillary permeability.

To evaluate the potential of centrifugal blood pumps for saving blood, 120 patients scheduled for elective coronary artery bypass grafting were entered into a prospective randomized trial. A standard roller pump (group I) was compared with a centrifugal blood pump (group II) and roller pump plus aprotinin (group III). There was no significant difference between groups I and II with respect to free haemoglobin, lactic dehydrogenase, serum bilirubin, platelet surface glycoprotein IIb-IIIa and granule membrane protein 140, chest-tube drainage, use of blood products, length of stay in intensive care, time on ventilator and postoperative mortality. Aprotinin reduced chest-tube drainage and use of blood products significantly. Three cases of graft occlusions were noted in group III. Centrifugal blood pumps offer no advantage in routine heart surgery over conventional roller pumps. Aprotinin reduces blood loss, but does not influence GP IIb-IIIa and GMP 140 expression on blood platelets.