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Background: Prompt and uneventful recovery after resective pulmonary surgery benefits patients by decreasing length and total costs of hospital stay. Postoperative physiotherapy has been shown to be advantageous for patient recovery in several studies and lately inspiratory muscle training (IMT) physiotherapy has been used also in thoracic patients. This randomized controlled trial intended to evaluate whether IMT is an efficient and feasible method of physiotherapy compared to water bottle positive expiratory physiotherapy (PEP) immediately after lung resections. Methods: Forty-two patients were randomly allocated into two intervention groups: water bottle PEP (n=20) and IMT group (n=22). Patients were given physiotherapeutic guidance once a day and patients were also instructed to do independent exercises. Measurements of pulmonary function were compared between the treatment groups according to intention to treat by using two-way repeated measures analysis of variances at three time points (preoperative, first postoperative day, and second postoperative day). Walking distance was measured at first and second postoperative day and similarly, evaluation of postoperative air leak during exercises was performed. Physiotherapy was modified or temporarily interrupted, if necessary, because of the air leak. Results: Postoperative pulmonary function tests were equal between the intervention groups. Air leak was relatively common after lung resections: 31% of all patients had mild or moderate/severe air leak at first postoperative day and 14% of all patients had mild to severe air leak at second postoperative day respectively. There were no statistically significant differences in occurrence of air leak between intervention groups, but water resistance had to be reduced or physiotherapy discontinued significantly more often among the water bottle PEP group patients (P=0.01). Walking distance improved slightly faster in the IMT group between the first and the second postoperative day when compared to the water bottle PEP group, but the difference between the groups was not statistically significant. Conclusions: IMT physiotherapy is equally effective to water bottle PEP training in postoperative physiotherapy after lung resection surgery evaluated with pulmonary function tests and walking distance. In addition, IMT physiotherapy is safe and more feasible form of physiotherapy during postoperative air leak compared to water bottle PEP. publishedVersion

Background: Two respiratory physiotherapy modalities were compared in a randomized controlled trial on patients undergoing minor pleuro-pulmonary surgery. Methods: Forty-five patients were randomly allocated into positive expiratory pressure (PEP) therapy (n=23) and inspiratory muscle training (IMT) groups (n=22). Individualized group specific physiotherapeutic guidance was administered preoperatively, and once a day postoperatively. Patients also performed independent exercises and kept a logbook. Pain was assessed on a numerical reference scale (NRS). Volumetric pulmonary function values and walking distance were recorded preoperatively, and on first (POD1) and second postoperative days (POD2). Pre- and postoperative values were compared using two-way repeated measures analysis of variance. Results: Patient characteristics and pleuro-pulmonary interventions were similar between the groups. Thoracotomy was performed in 14/45 and video assisted surgery (VATS) in 31/45 of cases. Preoperative volumetric pulmonary functions were normal or slightly decreased in 29/45, and fell significantly (P

Background: Over the years, frozen elephant trunk (FET) has become the treatment of choice for multisegmental thoracic aortic disease. This multicenter study presents the evolution of FET results using the E-vita Open hybrid graft with respect to institutional experience and time. Methods: The data of International E-vita Open registry were studied according to the institutional experience of the participating centers (high- versus low-volume centers) and according to the evolution of FET treatment during time (1st period, 2005-2011 versus 2nd period, 2012-2018). Overall, 1,165 patients were enrolled in the study with a wide variety of multisegmental thoracic aortic pathologies and aortic emergencies. Participating centers determined their own surgical protocol. Results: The overall 30-day mortality was 12%. Short- and long-term survival were higher in high- versus low-volume centers (P=0.048 and P=0.013, respectively). In the 2nd time period, cerebral complications were reduced significantly (P=0.015). Incidence of permanent spinal cord-related symptoms was reduced to 3% in the 2nd time period, but did not reach statistical significance. Hypothermic circulatory arrest time (P

Background and aims Focal adhesions (FA) play an important role in the tissue remodeling and in the maintenance of tissue integrity and homeostasis. Talin and vinculin proteins are among the major constituents of FAs contributing to cellular well-being and intercellular communication. Methods Microarray analysis (MA) and qRT-PCR low-density array were implemented to analyze talin-1, talin-2, meta-vinculin and vinculin gene expression in circulating blood and arterial plaque. Results All analyzed genes were significantly and consistently downregulated in plaques (carotid, abdominal aortic and femoral regions) compared to left internal thoracic artery (LITA) control. The use of LITA samples as controls for arterial plaque samples was validated using immunohistochemistry by comparing LITA samples with healthy arterial samples from a cadaver. Even though the differences in expression levels between stable and unstable plaques were not statistically significant, we observed further negative tendency in the expression in unstable atherosclerotic plaques. The confocal tissue imaging revealed gradient of talin-1 expression in plaque with reduction close to the vessel lumen. Similar gradient was observed for talin-2 expression in LITA controls but was not detected in plaques. This suggests that impaired tissue mechanostability affects the tissue remodeling and healing capabilities leading to development of unstable plaques. Conclusions The central role of talin and vinculin in cell adhesions suggests that the disintegration of the tissue in atherosclerosis could be partially driven by downregulation of these genes, leading to loosening of cell-ECM interactions and remodeling of the tissue.

Kindlins (FERMT) are cytoplasmic proteins required for integrin (ITG) activation, leukocyte transmigration, platelet aggregation and thrombosis. Characterization of kindlins and their association with atherosclerotic plaques in human(s) is lacking.Exploratory microarray (MA) was first performed followed by selective quantitative validation of robustly expressed genes with qRT-PCR low-density array (LDA). In LDA, ITGA1 (1.30-fold, p = 0.041) and ITGB3 (1.37-fold, p = 0.036) were upregulated in whole blood samples of patients with coronary artery disease (CAD) compared to healthy controls. In arterial plaques, both robustly expressed transcript variants of FERMT3 (MA: 5.90- and 3.4-fold; LDA: 3.99-fold, p0.0001 for all) and ITGB2 (MA: 4.81- and 4.92-fold; LDA: 5.29-fold, p0.0001 for all) were upregulated while FERMT2 was downregulated (MA: -1.61-fold; LDA: -2.88-fold, p0.0001 for both). The other integrins (ITGA1, ITGAV, ITGB3, ITGB5) were downregulated. All these results were replicated in at least one arterial bed. The latter FERMT3 transcript variant associated with unstable plaques (p = 0.0004). FERMT3 correlated with M2 macrophage markers and in hierarchical cluster analysis clustered with inflammatory and macrophage markers, while FERMT2 correlated with SMC-rich plaque markers and clustered with SMC markers. In confocal immunofluorescence analysis, FERMT3 protein colocalized with abundant CD68-positive cells of monocytic origin in the atherosclerotic plaques, while co-localization of FERMT3 with HHF35 indicative of smooth muscle cells was low.Kindlin-3 (FERMT3) is upregulated in atherosclerotic, especially unstable plaques, mainly in cells of monocytic origin and of M2 type. Simultaneous upregulation of ITGB2 suggests a synergistic effect on leukocyte adherence and transmigration into the vessel wall.

Background— Macrophage (MΦ) infiltration and smooth muscle cell (SMC) proliferation are hallmarks of atherosclerosis and unstable plaques. Neuroimmune guidance cue 1 (netrin-1 [NTN1]) plays a critical role controlling MΦ trafficking and SMC activation. Characterization of expression of NTN1 and its receptors and their association with plaque stability in human(s) is lacking. Methods and Results— The expression of NTN1 and its receptors did not differ in either whole blood or circulating monocytes from patients with coronary artery disease (n=55) compared with healthy controls (n=45). However, NTN1 was downregulated (−2.9-fold; P P P =0.011). NTN1 expression correlated positively with SMC markers and signatures and negatively with inflammatory markers and M1 and especially M2 signatures in the atherosclerotic plaques. UNC5B clustering correlated positively with inflammatory and MΦ markers. NTN1 protein colocalized with CD68-positive cells of monocytic origin and muscle-actin-specific-antibody (HHF3)-positive cells indicative of SMCs in the plaques and only with SMCs in the control samples. NTN1 protein was highly expressed in the intimal layer of the control vessels. Conclusions— Present findings provide support for the hypothesis that dysregulation of expression of NTN1 in SMCs and its chemorepulsive receptor UNC5B in macrophages are involved in the development of atherosclerosis and unstable plaques.

Aim: To determine whether an electronic nose can differentiate cultured nonmalignant and malignant prostatic cells from each other and whether the smell print is secreted to the surrounding medium. Materials & methods: Prostatic nonmalignant (EP-156T and controls) and malignant (LNCaP) cell lines, as well as conditioned and unconditioned media, were collected. The smell prints of the samples were analyzed by a ChemPro® 100 electronic nose device. The data were normalized and dimension reduction was conducted. The samples were classified and misclassification rates were calculated. Results: The electronic nose differentiated the nonmalignant and malignant cell lines from each other, achieving misclassification rates of 2.9–3.6%. Cells did not differ from the conditioned medium but differed from the unconditioned medium (misclassification rates: 0.0–25.6%). Conclusion: Malignant and nonmalignant prostatic cell lines have distinct smell prints. Prostatic cancer cells seem to modify the smell print of their medium.

Summary Objective Hospital mortality and long-term survival in major cancer surgery seems to be affected by hospital related factors. We evaluated the effect of university versus non-university hospital type, and surgical volume (0–4, 5–10, 11–20, and >20 average of cases/year) on the immediate and long-term survival of surgical non-small cell lung cancer (NSCLC) patients. Patients and methods Between 1988 and 2002, the number of NSCLC resections with curative intent in Finland was 5339. Follow-up until the end of 2003 from national registries was available on 91% (4878 of 5339) of patients. Results Multivariate analysis showed that hospital mortality was unaffected by hospital type or volume, but delay of >4 months from diagnosis to surgery did have an adverse effect. Surgery at university hospitals was associated with significantly better cancer-related and overall survival, as also was surgery at very low-volume but mainly private hospitals (0–4 cases/year). Conclusions Undergoing surgery for non-small cell lung cancer at a university hospital may offer an advantage for long-term survival, but large hospital volume in itself did not. Summary Multivariate analysis on the effect of hospital type and surgical volume on immediate and long-term survival of 4878 lung cancer surgery patients, 1988–2002, showed that surgery at university hospitals was associated with significantly better cancer-related and overall survival, but hospital mortality did not differ. Large hospital volume did not independently predict a better outcome.

OBJECTIVES: Providing effective treatment for complicated type B aortic dissection (AD) with concomitant pathologies of the aortic arch or ascending aorta is challenging, especially if the aortic anatomy is contraindicated for thoracic endovascular aortic repair (TEVAR). We present the early results of a multicentre study using the frozen elephant trunk (FET) technique for type B AD. METHODS: From January 2005 to March 2013, data from 465 patients who had undergone treatment with the FET technique were collected in the database of the International E-vita Open Registry. From this cohort, 57 patients who had a primary indication for surgery for type B AD were included in the present study. Their mean age was 58 ± 12 years, and 72% had a chronic dissection. All operations were performed in circulatory arrest and bilateral antegrade cerebral perfusion. Computed aortic imaging was performed for false lumen (FL) evaluation during the follow-up. RESULTS: The in-hospital mortality rate was 14% (8/57). Stroke and spinal cord injury occurred in 6 (10%) and 2 patients (4%), respectively. The rate of immediate FL thrombosis at the level of the stent graft was 75% (40/53) and increased to 97% (41/42) during the follow-up period (23 ± 19 months). Distally, at the level of the abdominal aorta, the FL remained patent in 50% (21/42) of patients. The 1- and 3-year survival was 81 and 75%, respectively. CONCLUSION: The FET technique is a feasible therapeutic option for complicated type B AD with involvement of the aortic arch if TEVAR is contraindicated. In contrast to conventional aortic surgery via a lateral thoracotomy, the FET procedure can provide simultaneous treatment of the ascending aorta and aortic arch.

High mobility group A (HMGA) proteins play an important role in the regulation of transcription, differentiation, and neoplastic transformation. In this work, the expression of HMGA 1 and 2 in 152 lung carcinomas of mainly non-small-cell histological type has been studied by immunohistochemistry in order to evaluate their feasibility as lung cancer markers. In 17 lung cancer cases, the related bronchial epithelial changes were also studied for HMGA1 and 2 expression. RNA expression of HMGA1a and b isoforms and of HMGA2 was determined by real-time semi-quantitative RT-PCR in 23 lung carcinomas. High expression of HMGA1 and HMGA2 at both mRNA and protein levels was detected in lung carcinomas, compared with normal lung tissue. Nuclear immunostaining for HMGA1 and 2 proteins also occurred in hyperplastic, metaplastic, and dysplastic bronchial epithelium. Increased nuclear expression of HMGA1 and 2 correlated with poor survival (for adenocarcinomas, HMGA1, p = 0.006; HMGA2, p = 0.05). While the expression of HMGA2 was significantly associated with cell proliferation (p = 0.008), HMGA1 expression did not show any association with proliferation or apoptotic index. Sequencing of HMGA2 transcripts from tumours with very high expression showed a normal full-length transcript. As HMGA proteins were expressed in about 90% of lung carcinomas and their expression was inversely associated with survival, they may provide useful markers for lung cancer diagnosis and prognosis. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

ObjectivesWe sought to compare the clinical profile and outcomes of operations for aortic valve disease and ascending aortic aneurysm in patients treated with aortic valve replacement and supracoronary replacement of the ascending aorta or composite replacement of the aortic valve and ascending aorta (Bentall operation).MethodsFrom 1990 through 2001, 133 patients had aortic valve replacement and supracoronary replacement of the ascending aorta, and 452 patients had Bentall operations. Aortic valve replacement and supracoronary replacement of the ascending aorta was performed in patients who had aortic valve disease and dilation of the ascending aorta, whereas the Bentall operation was performed in patients with aortic root abnormality and ascending aortic aneurysm. Mean follow-up was 4.6 ± 3.1 years and was 100% complete.ResultsPatients who had aortic valve replacement and supracoronary replacement of the ascending aorta were older (61 ± 13 vs 52 ± 16 years, P < .001) and more likely to have aortic stenosis, coronary artery disease, and mitral valve disease than those who had Bentall operations. The use of mechanical valves was equal in both groups (42% for aortic valve replacement and supracoronary replacement of the ascending aorta and 43% for the Bentall operation). Operative mortality was 5% for patients undergoing aortic valve replacement and supracoronary replacement of the ascending aorta and 4% for patients undergoing the Bentall operation (P = .45). Survival at 10 years was 57% ± 8% for patients undergoing aortic valve replacement and supracoronary replacement of the ascending aorta and 74% ± 4% for patients undergoing the Bentall operation (P = .04), but the type of operation had no effect on survival. Older age, moderate or severe left ventricular dysfunction, active endocarditis, previous cardiac surgery, and coronary artery disease were independent predictors of death. The freedom from reoperation at 10 years was 95% ± 5% for patients undergoing aortic valve replacement and supracoronary replacement of the ascending aorta and 94% ± 3% for patients undergoing the Bentall operation (P = .18). Reoperations were mostly because of tissue valve failure or endocarditis. The risk of valve-related complications was the same in both groups. No patient required reoperation for aortic root aneurysm after having aortic valve replacement and supracoronary replacement of the ascending aorta.ConclusionsAortic valve replacement and supracoronary replacement of the ascending aorta and the Bentall operation provide comparable long-term results. The Bentall operation is more appropriate for patients with aortic root abnormality and a dilated ascending aorta, whereas aortic valve replacement and supracoronary replacement of the ascending aorta is a perfectly acceptable operation for patients with aortic valve disease, normal or mildly dilated aortic sinuses, and a dilated ascending aorta.

To identify new potential diagnostic markers for lung cancer, the expression profiles of 37 lung tumours were analysed using cDNA arrays. Seven samples were from small-cell lung cancer (SCLC), two from large-cell neuroendocrine tumours (LCNEC), and 28 from other non-small-cell lung cancers (mainly squamous cell cancer and adenocarcinoma). Principal component analysis and the permutation test were used to detect differences in the gene expression profiles and a set of genes was found that distinguished high-grade neuroendocrine carcinomas (SCLC and LCNEC) from other lung cancers. In addition, several genes, such as caveolin-1 (CAV1) and caveolin-2 (CAV2), were constantly deregulated in all types of tumour sample, compared with normal tissue. The expression of these two genes was investigated further at the protein level on a tissue microarray containing tumours from 161 patients and normal tissues. Immunostaining for CAV1 was negative in 48% of tumours, whereas 28% of the tumours did not express CAV2. Lack of CAV1 protein expression was not caused by methylation or mutation. In stage I adenocarcinomas, CAV2 protein expression correlated with shorter survival. In conclusion, the present study was able to identify genes that have not previously been implicated in lung cancer by the combined use of two different array techniques. Some of these genes may provide novel diagnostic markers for lung cancer. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Objectives The treatment of patients with extensive thoracic aortic disease involving the arch and descending aorta is often performed, using the frozen elephant trunk (FET) technique. We retrospectively analysed early outcomes with this technique, using a prospective database. Methods A total of 509 patients (mean age: 61 ± 11 years) were registered between January 2005 and January 2014 in a multicentre database after FET surgery. Acute or chronic aortic dissection (AD) was the indication for surgery in 350 (68.8%) patients and degenerative or atherosclerotic aneurysm (DA) accounted for 159 (31.2%) patients. A logistic regression model was created to identify independent predictors of in-hospital mortality and neurological complications. Results The average in-hospital mortality was 15.9% (n = 81) with 17.1% for AD patients and 13.2% for DA patients (P = 0.2). Independent predictors of in-hospital mortality were haemodynamic instability [odds ratio (OR): 2.7, P = 0.005], peripheral vascular disease (OR: 2.6, P = 0.002), diabetes (OR: 2.1, P = 0.05) and selective cerebral perfusion time >60 min (OR: 2.2, P = 0.005). Patients under 60 years of age and the use of guide wire during FET implantation were protective for early survival. Stroke occurred in 7.7% (n = 39) of patients. Paraplegia or paraparesis occurred in 7.5% (n = 38) of patients. A distal landing zone lower than T10 was an independent predictor for spinal cord injury (OR: 2.3, P = 0.03). Conclusions Techniques for faster arch replacement and controlled FET placement should be considered in order to reduce the early mortality and neurological complications after FET surgery. For distal aortic lesions, a two-staged approach is suggested, rather than the FET landing lower than T10.

Definitive treatment of extended thoracic aortic dilatation is a major surgical challenge. Histopathology of resected thoracic aortic wall may reveal undiagnosed aortitis affecting outcome. We sought to investigate the benefit of thorough histopathology after one-stage corrective surgery for the treatment of extended thoracic aortic dilatation. Five patients underwent one-stage corrective surgery using the hybrid open arch repair by the frozen elephant trunk together with endovascular aortic grafting. A representative sample of the resected aortic arch was procured for histology. T- and B-lymphocytes, plasma cells, macrophages, and immunoglobulin G4 (IgG4) positivity were evaluated by immunohistochemistry. The mean preoperative maximum aortic diameter was 54 mm (range, 41–79 mm). The mean follow-up was 18 months (range, 1–24 months). As confirmed by computed tomography (CT) upon follow-up, complete thrombosis of the false lumen at the level of the frozen elephant trunk was achieved in all patients with dissection. One patient was operated due to atherosclerotic dilatation of the thoracic aorta, and postoperative CT showed successful exclusion of the atherosclerotic dilatation; this 75-year-old man was diagnosed with IgG4-positive aortitis and experienced unexpected blindness after surgery without evidence of emboli or long-term neurological impairment upon repeated brain CT. The hybrid open arch repair by the frozen elephant trunk and simultaneous endovascular repair is a feasible choice for one-stage surgery through sternotomy aiming at definitive treatment of extended thoracic aortic pathology. However, systematic evaluation of inflammation may reveal concealed aortitis affecting postoperative outcome and need for long-term surveillance.

Pulmonary arteriovenous malformations are rare, mostly asymptomatic vascular anomalies. These malformations cause direct right to left shunting of unoxygenated blood, resulting chronically in cyanosis, dyspnea, and exercise intolerance. The serious complications reported earlier have mainly been neurologic, for example, cerebrovascular accidents and brain abscesses and are most likely caused by paradoxical embolism. Detection of pulmonary arteriovenous malformations is challenging, and the emergency department personnel play an essential role. Once suspected, the diagnosis can be made promptly using standard imaging techniques and appropriate treatment may prevent serious complications. In this report, we describe a case of a 41-year-old man with acute anterior myocardial infarction, unexpectedly caused by emboli from pulmonary arteriovenous malformations. This rare etiology of acute myocardial infarction should be taken into consideration especially in cases with atypical presentation.

Aims Talc pleurodesis using talc slurry via chest tube is a primary option in malignant pleural effusion, since life expectancy is short and surgical decortication is hazardous. Incomplete lung expansion after fluid evacuation, and/or excessive fluid secretion predicts failure of pleurodesis. A mini-invasive alternative was investigated. Methods Between March 2004 and September 2005, 51 consecutive patients with malignant pleural effusion, and clinically considered unsuitable for talc pleurodesis, received an indwelling pleural catheter (Denver PleurX). In 47, implantation was done bedside using local anaesthesia. There were 24 men and 27 women, median age 63 (range 36–85) years, receiving 39 right side, 10 left side, and 2 bilateral catheters. There were 19 non-small cell lung cancer cases, 7 mesothelioma, and 25 with other malignancy. Chemotherapy was being given to 18 patients and was not interrupted. Results Discharge to home was possible in 71% (36 of 71 patients) on the following day. At 2 years follow-up in September 2007, one patient was alive. Mean survival was 3 months (range 5 days to 37+ months) for all patients, with best median survivals of 5.5–6 months in breast and ovarian cancer. Catheter was removed or replaced in 15% (8 of 51 patients) due to infection, air leak, or blockage. One patient requested decortication for excessive fluid secretion. None required surgery or died due to catheter-related complications. Pleural fusion with subsequent catheter removal was achieved in 21% (11 of 51 patients). Conclusions An indwelling pleural catheter is a safe alternative for patients with malignant pleural effusion unsuitable for talc pleurodesis. In some, pleural fusion may be achieved.

Objective: To compare computed tomography (CT)-based clinical TNM and staging to surgical-pathological staging with systematic lymph node dissection in primary non-small cell lung cancer. Methods: The study included 49 non-small cell lung cancer patients that underwent lung resection and systematic lymph node dissection between 1997 and 2001. Preoperative clinical and CT findings were compared with surgical-pathological findings. Lymph nodes with a shortest diameter of over 1 cm on CT were considered abnormal, but did not contraindicate surgery. Patients with CT indicating an invasive T4 tumor, pleural carcinosis, or bulky N2 disease were excluded. Results: Sixty-five percent (32/49) had epidermoid carcinoma, and 25% (12/49) had adenocarcinoma. N2 metastases were found in 12% (6/ 49). The clinical T category was correct in 71% (35/49), and the N category in 55% (27/49). The sensitivity for detecting N2 disease was 67% (4/6), and the spesificity was 81% (35/43). The positive predictive value for N2 disease was 33% (4/12), and the negative predictive value was 95% (35/37). Node-by-node agreement on N2 metastatic location was 17% (1/6). Skip N2 metastases without any N1 involvement were found in 4% (2/49), or 33% (2/6) of all N2 cases. The clinical stage was correct in 45% (22/49), and complete TNM agreement was 37% (18/ 49). Conclusions: The clinical TNM and staging based on CT are inaccurate. The sensitivity for detecting N2 disease is poor, especially on node-by node basis. Preoperative exclusion of N2 metastases is quite reliable, but a positive finding should always be verified. Systematic mediastinal lymph node dissection is necessary to detect N2 metastases inaccessible to cervical mediastinoscopy, and skip N2 metastases without N1 involvement. q 2002 Elsevier Science B.V. All rights reserved.

The FHIT gene, at 3p14.2, has been suggested to form a molecular target to damage induced by human lung carcinogens. We examined aberrant expression of the Fhit protein and allele loss at the FHIT gene in a series of lung cancer cases, mainly of non-small cell carcinoma (NSCLC) histology. We had detailed data on tobacco smoke exposure and occupational asbestos exposure available for the cases. The principal aim of the present study was to investigate whether absent or reduced Fhit expression or FHIT allele loss was associated with exposure to these pulmonary carcinogens. We detected reduced Fhit expression in 62% (33/53) of the cases analysed. Prevalence of allele loss at the FHIT locus was 22% (20/89). Reduced protein expression was common both in the asbestos-exposed (67%) and non-exposed cases (59%); [odds ratio (OR) 1.4, 95% confidence interval (CI) 0.4-4.9]. LOH frequencies differed somewhat between the two groups and were 25% vs. 16%, respectively (OR 1.8; 95% CI 0.5-5.9). Absent or reduced expression was common in smokers, with no significant difference found between current smokers and non-smokers (mainly former smokers) (OR 1.4, 95% CI 0.5-4.5). NSCLCs with squamous cell histology exhibited both aberrant expression (OR 3.1, 95% CI 0.9-10.3) and allele loss (OR 3.3, 95% CI 0.9-12.7) more frequently than adenocarcinoma. Finally, we found that FHIT allele loss was increased in stage II or more advanced disease (OR 2.5, 95% CI 0.9-7.4), and in poorly differentiated tumours (grade 3, OR 2.6, 95% CI 0.8-8.1). In conclusion, our present data support significance of FHIT inactivation in development of lung cancer.

To detect lymph node metastases by immunohistochemistry, where previously undetected by routine histopathology.Immunostaining was carried out for high- and low molecular weight cytokeratins, and Ber-EP4 in 19 consecutive lung cancer patients who had undergone systematic mediastinal lymph node dissection.Eleven (58%) epidermoid carcinomas, 6 (32%) adenocarcinomas, and 2 (10%) bronchiolo-alveolar carcinomas were detected. These included 4 (21%) stage IA carcinomas, 6 (32%) stage IB, 6 (32%) stage IIB, 1 (5%) stage IIIB and 2 (10%) stage IV. Immunostaining did not reveal any undetected metastases. Two patients (squamous cell carcinoma T1N0; adenocarcinoma T1N0) had metastases (skeletal; ipsilateral lung) at time of surgery, and one patient (squamous cell carcinoma T2N0) had a regional and systemic relapse 10 months later. Serial sectioning with immunostaining of the lymph nodes from these three patients was also negative.We conclude that, even with the use of immunostaining, negative lymph nodes will not assure a good prognosis, and different determinants probably exist for lymphatic and hematogenic metastases in non-small cell lung cancer.

Validated markers are needed to identify operable lung cancer patients with poor prognosis. About one-half of non-small-cell lung cancers (NSCLCs) carry a mutation in the p53 tumor-suppressor gene. We examined 101 NSCLC patients for surgical stage, completeness of resection, tobacco smoking, asbestos exposure, age, gender and p53 gene mutations as prognostic factors after a follow-up period of 4 years. Cox's multivariate regression model was applied to quantify the associations with overall and cancer-related survival. Patients with a wild-type p53 gene had an overall 4-year survival of 43% and those with a mutated p53 gene, 35%. In squamous-cell carcinoma, stage and heavy smoking, defined as the median of pack-years smoked, had prognostic significance for overall survival. Only stage was associated with poor cancer-related survival. Asbestos exposure was not associated with overall survival or cancer-related survival in squamous-cell carcinoma or adenocarcinoma. In adenocarcinoma, p53 mutation, in addition to stage, emerged as a significant predictor of poor cancer-related survival.

In order to assess the appropriateness of lung cancer surgery in the elderly and determine optimal subjects and resection procedure, 75 patients operated on in 1976-1996 at age > or =75 years (including 13 > or =80) were followed up. The operations included limited resection (8), lobectomy (47), bilobectomy (10) and pneumonectomy (10) and were judged to be radical in 59 cases (79%). Perioperative mortality was 9% and morbidity 29%, including 21% major complications. Cumulative 5-year survival was 32%, in stages IA-IIB 27-41%, and cancer-related survival 61-79%. Mortality did not differ significantly between resection types, but morbidity did. Nor did mortality, morbidity or survival differ between the age groups 75-79 and > or =80 years. In stage I cancer there was no significant difference in survival or cancer-related survival after lobectomy vs limited resection. We conclude that age, even >80 years, is not incompatible with curative resection. Lobectomy is the treatment of choice, but a less radical resection may be advisable if there is comorbidity. If more extensive resection is performed, the individual surgical risk must be weighed against the potential long-term benefit.

Over the past decade, the self-expanding metallic stent (SEMS) has been considered a safe and effective modality for treatment of inoperable malignant and selected benign airway diseases. Cases of life-threatening or massive hemoptysis have, however, occurred after placement of firstgeneration tracheal SEMSs. We report a case in which a secondgeneration tracheal SEMS caused ulcer formation and a fistula between the trachea and the brachiocephalic artery 40 months after insertion and discuss the cause, pathogenesis, and clinical features of the massive airway bleeding.