[Surgical staging of lung cancer]. / Thoraxchirurgisches Staging des Lungenkarzinoms.

Proper staging of lung cancer represents the basis for any stage-adapted and optimized treatment. This is today implemented in specialized centers mainly through the use of modern imaging methods and minimally-invasive measures. However, general thoracic surgery has a role not only in the therapeutic management of lung cancer, but offers additional staging information whenever endoscopic or interventional methods fail to achieve representative tissue biopsies of mediastinal lymph nodes or suspect lesions for conclusive diagnosis. The thoracic surgical armentarium comprises of cervical or extended mediastinoscopy, video-assisted mediastinal lymphadenectomy (VAMLA), anterior mediastinotomy (Chamberlain procedure) and video-thoracoscopy (VATS). Indications for any invasive diagnostic methods always have to respect a therapeutic benefit for the patient.

Serum integrin-linked kinase (sILK) concentration and survival in non-small cell lung cancer: a pilot study.

BACKGROUND: Integrin-linked kinase (ILK) is an intracellular signaling protein critically involved in cellular growth and motility. In non-small cell lung cancer (NSCLC), increased ILK expression has been associated with decreased recurrence-free and overall survival. Recently, ILK has also been detected in the serum of NSCLC patients. OBJECTIVE: To assess the prognostic impact of preoperative serum ILK (sILK) concentration on overall survival in surgically amenable NSCLC. PATIENTS AND METHODS: Preoperative sILK was quantified by ELISA in 50 newly diagnosed NSCLC patients. After surgery, patients were followed-up for a median interval of 2.5 years. RESULTS: Serum ILK concentrations ranged from 0 to 2.44 ng/ml. Mean sILK was around 2.3 times higher in the 16 patients who died as compared to the 34 patients who survived (1.04 vs. 0.45 ng/ml, p = 0.001). In univariate time-to-event analysis, increased sILK was associated with adverse survival [Hazard ratio (HR): 4.03, 95 % CI: 2.00-8.13, p < 0.001]. This association prevailed after multivariable adjustment for several clinical, demographic, and laboratory parameters (HR: 3.85, 95 % CI: 1.53-9.72, p = 0.004). CONCLUSIONS: Serum ILK shows potential as a novel strong and independent prognostic marker for postoperative survival in surgically amenable NSCLC.

Resistance to EGFR targeting therapies in lung cancer.

The treatment of advanced non-small cell lung cancer (NSCLC) by therapies targeting the epidermal growth factor receptor (EGFR) pathway represents one of the most important advances in thoracic oncology. Reversible EGFR tyrosine kinase inhibitors (TKIs), like gefitinib and erlotinib, are able to achieve dramatic responses in a subset of patients. However, most patients treated with TKIs eventually develop resistance against these drugs. Here we review the physiology and pathology of EGFR activation in NSCLC, the clinical experience with TKIs, the mechanisms of resistance against TKIs, and discuss various approaches to treat resistance against TKIs.

Hypoxia induces heat shock protein expression in human coronary artery bypass grafts.

OBJECTIVE: Heat shock proteins (HSPs) are molecular chaperones which are essential for cell survival. Heat shock and hypoxia markedly increase the expression of several HSPs in various tissues, i.e. heart. In our in vitro study, we investigated whether HSPs are inducible in human vessels which are used as coronary artery bypass grafts. METHODS: We used remnants of the saphenous vein and the internal mammary artery from 34 patients undergoing coronary artery bypass surgery. Each vessel was divided into segments, one for control conditions at 37 degrees C (5% CO(2)-95% air), the remaining ones for thermal (30 min at 42 degrees C) or hypoxic treatment (6 h oxygen deprivation with nitrogen). The expression of Hsp60, Hsp72 and Hsp73 was investigated by immunohistochemistry and Western-blot analysis. RESULTS: Compared to controls, segments of the saphenous vein undergoing heat treatment showed significantly increased expression of Hsp72 in the intima (P=0.035) and Hsp73 in the media (P=0.003). In the internal mammary artery, Hsp72 and Hsp73 were expressed in the intima at significantly higher levels (P=0.042 each). A 6 h oxygen deprivation with nitrogen resulted in elevated levels of Hsp60 (media: P=0.048), of Hsp72 (intima: P<0.001 and media: P=0.004) and of Hsp73 (intima: P=0.029) in the saphenous vein. In the internal mammary artery, Hsp73 expression was significantly enhanced (intima: P=0.048 and media: P=0.017). The results were confirmed by Western-blot analysis in representative veins. CONCLUSIONS: These findings demonstrate the common cellular defense mechanism of HSP expression in response to stress in coronary artery bypass grafts. Hypoxia and heat treatment strongly induce Hsp72 and Hsp73 expression in human coronary artery bypass grafts.

Selection of viable cardiomyocytes for cell transplantation using three-dimensional tissue culture.

BACKGROUND: We developed a three-dimensional cardiac tissue culture system to select viable and contractile cells for the purpose of cardiomyocyte transplantation. In this study we will show that reaggregation of cardiomyocytes in culture is an active process indicative of cardiomyocyte viability and functionality. METHODS: Myocardial tissue from newborn mice has been enzymatically digested, incubated in culture inserts, and studied by phase contrast microscopy, conventional histology, immunohistochemistry, electron microscopy, and TUNEL assay. RESULTS: Cells that are plated on nonadhesive surfaces, reaggregate to spontaneously contracting cell aggregates. The capacity to reaggregate was significantly dependent from the age of the tissue donor (P<0.0001) and on the method of enzymatic dissociation (P<0.0001). The majority of cells within the aggregates consisted of cardiomyocytes. After 24 hr incubation, significant amounts of laminin and fibronectin had been deposited between the cells. Ultrastructural analysis revealed viable cardiomyocytes attached to each other by tight junctions. The apoptotic rate within the aggregates was 11.4+/-4.6 vs. 44.5+/-10.5% immediately after dissociation (P<0.05). CONCLUSIONS: The capacity to form spontaneously contracting aggregates is an inherent characteristic of viable cardiomyocytes in 3-dimensional cultures, which could be successfully exploited for cellular cardiomyocyte transplantation.

Primum atrial septal defect in children: early results, risk factors, and freedom from reoperation.

BACKGROUND: Repair of primum atrial septal defect in children usually is associated with a low operative mortality, except for a subgroup of children with congestive heart failure. To determine the early mortality and incidence of reoperation in children with primum atrial septal defect, we analyzed retrospectively the results of patients who underwent repair of this defect. METHODS: Between July 1982 and December 1996, 180 children underwent repair of primum atrial septal defect. The mean age at repair was 4.6 years (median, 3.6 years; range, 1 month to 16.4 years); of the 180 children, 23 were infants less than 1 year of age. Absent or mild symptoms were present in 145 (80%), whereas 34 (20%) of children presented with severe symptoms or congestive heart failure. RESULTS: Early mortality occurred in 3 (1.6%); 2 were less than 1 year of age. Follow-up ranged from 2 months to 14.5 years (mean, 6 +/- 4.2 years). Actuarial survival is 98% at 10 years with no late deaths. Age less than 1 year is a predictor of death. During follow-up, 17 (9%) of the 180 patients underwent reoperation, 5 of whom were in the infant group. Five underwent reoperation for subaortic obstruction, and 12 for left atrioventricular valve regurgitation of whom 11 were repaired; and 1 required valve replacement. Age and preoperative moderate-to-severe left atrioventricular valve regurgitation were predictors of reoperation. CONCLUSIONS: Results of the repair of primum atrial septal defect during childhood are favorable. Infants have a higher risk for death and reoperation. Left atrioventricular valve insufficiency and subaortic stenosis are important late complications and can be repaired safely at reoperation.