Gunnar Myrdal

Quality of life following lung cancer surgery

Background: Patients with non-small cell bronchogenic carcinoma have a limited survival. Quality of life (QoL) is therefore an issue of importance in this group of patients. The aim of the present study was to evaluate QoL in lung cancer patients after open surgery. Methods: During a 4 year period (1997–2000) 194 patients with primary bronchogenic carcinoma of the lung underwent surgery at the Department of Thoracic and Cardiovascular Surgery in Uppsala, Sweden; 132 patients were alive on 1 April 2001. These patients received the Short Form-36 (SF-36) health questionnaire, Hospital Anxiety and Depression (HAD) scale, and special questions related to pulmonary symptoms (response rate 85%). Patients who underwent coronary bypass surgery (CABG) served as a comparison group (response rate 91%). Corresponding estimates of QoL in healthy controls were obtained from the SF-36 manual for the Swedish population. Results: Lung cancer patients differed from CABG patients in only one subgroup of the SF-36 (role physical), but had poorer QoL than healthy controls. No difference in anxiety was found between the lung cancer patients and the CABG patients, but the latter were more likely to suffer from depression (5.0% v 3.0%). Current smokers scored lower in the mental health dimension assessment. Conclusion: Lung cancer patients who undergo open traditional surgical resection have a QoL comparable to that of CABG patients. Lung cancer patients have poorer physical function because of reduced pulmonary function, but show no sign of increased anxiety or depression. Those who continued to smoke after surgery had impaired mental health.

Outcome after lung cancer surgery. Factors predicting early mortality and major morbidity

OBJECTIVE This study was undertaken to assess mortality, complications and major morbidity during the first 30 days after lung cancer surgery and to estimate the significance of presurgical risk factors. METHODS The study was based on all patients referred for surgery for primary lung cancer from 1 January 1987 to 1 September 1999. There were in total 616 patients with primary lung cancer. Three-hundred and ninety-four were men and 222 women. Postoperative events studied were divided into major and minor complications or death during the first 30 days after surgery. The significance of risk factors for an adverse outcome (defined as death or major complication in the first 30 days postoperatively) was assessed by uni- and multivariate logistic regression analyses. RESULTS During the study period an increasing number of women and of patients older than 70 years underwent surgery. Overall 30-day mortality was 2.9, 0.6% after single lobectomy and 5.7% after pneumonectomy. Major complications occurred in 54 patients (8.8%). Fifty-eight patients (9.5%) had an adverse outcome during the first 30 days. Male gender, smoker, FEV(1)< or =70% of expected value, squamous cell carcinoma and pneumonectomy were risk factors predicting adverse outcome in the univariate model. Pneumonectomy and FEV(1)< or =70%, were the only independently significant factors for adverse outcome. Only pneumonectomy was independently associated with an increased risk for early death. CONCLUSION Our results show low mortality and morbidity after lung cancer surgery. However, patients with reduced lung capacity and those undergoing pneumonectomy should be treated with great care, as they run a considerable risk of major complications or death during the first 30 days postoperatively. Older age (>70 years) does not appear to be a contraindication to lung cancer surgery, but patients in this group should undergo careful preoperative evaluation.

Regional differences in treatment and outcome in non-small cell lung cancer: A population-based study (Sweden)

In the recent decade uniform treatment guidelines for non-small cell lung cancer (NSCLC) have been introduced in Sweden. The objective of this study was to examine time trends and differences in treatment intensity for NSCLC between county clinical centres in Central Sweden. A second aim was to investigate whether any differences in treatment of NSCLC were associated with differences in survival. 4345 patients with a diagnosis of NSCLC between 1995 and 2003 were identified in the population-based Lung Cancer Register of Central Sweden. Multivariate logistic regression was used to estimate odds ratios to analyse the likelihood of receiving different treatment modalities for NSCLC. Cox proportional hazard models estimating relative hazard ratios were used to identify factors related to death (by any cause). Of all patients, 33.4% received no treatment, and 17.5% underwent surgery. Between 1995 and 2003, the proportion of patients receiving chemotherapy rose from 14.6% to 55%. There were pronounced differences between county centres in treatment policies, especially concerning surgery and radiotherapy. The likelihood of receiving treatment for NSCLC was highest at county centre A where both surgical treatment and chemotherapy were given more often. Compared to this reference county, the risk of death was between 20% and 40% higher in the other counties after adjusting for age, stage, gender, time period, smoking status and histopathological type. When analyses were adjusted for treatment, county of residence was no longer a prognostic factor. Despite common guidelines there were marked differences in treatment activity between the counties. Treatment activity was associated with survival. Survival benefits may follow improvement in compliance to guidelines.

Gene copy number aberrations are associated with survival in histologic subgroups of non-small cell lung cancer.

Introduction: Non-small cell lung cancer (NSCLC) is characterized by a multitude of genetic aberrations with unknown clinical impact. In this study, we aimed to identify gene copy number changes that correlate with clinical outcome in NSCLC. To maximize the chance to identify clinically relevant events, we applied a strategy involving two prognostically extreme patient groups. Methods: Short-term (<20 month; n = 53) and long-term survivors (>58 month; n = 47) were selected from a clinically well-characterized NSCLC patient cohort with available fresh frozen tumor specimens. The samples were analyzed using high-resolution single-nucleotide polymorphism array technology to assess gene copy number variations and array-based gene expression profiling. The molecular data were combined with information on clinical parameters. Results: Genetic aberrations were strongly associated with tumor histology. In adenocarcinoma (n = 50), gene copy number gains on chromosome 8q21-q24.3 (177 genes) were more frequent in long-term than in short-term survivors. In squamous cell carcinoma (n = 28), gains on chromosome 14q23.1-24.3 (133 genes) were associated with shorter survival, whereas losses in a neighboring region, 14q31.1-32.33 (110 genes), correlated with favorable outcome. In accordance with copy number gains and losses, messenger RNA expression levels of corresponding genes were increased or decreased, respectively. Conclusion: Comprehensive tumor profiling permits the integration of genomic, histologic, and clinical data. We identified gene copy number gains and losses, with corresponding changes in messenger RNA levels that were associated with prognosis in adenocarcinoma and squamous cell carcinoma of the lung.

Survival in primary lung cancer potentially cured by operation: influence of tumor stage and clinical characteristics.

BACKGROUND Surgical resection is currently standard treatment in early stage lung cancer. The aim of the present study was to identify stage-related factors and patient characteristics influencing survival after complete resection. METHODS We identified 395 patients with non-small cell lung cancer who had undergone potentially radical operation during 1987 to 1999 at one thoracic surgery institution in central Sweden. Factors independently related to survival were identified in a multivariate analysis. Survival was analyzed in low-, medium-, and high-risk groups based on a risk score calculated from relative hazards for identified risk factors. RESULTS Overall 5-year survival among the 395 patients was 51%. The strongest factor predicting prognosis was positive lymph nodes at operation. Higher age, earlier period for operation, impaired lung function, current smoking, and major operative complication were all related to poorer prognosis. Patients with tumor stage Ia had a 5-year survival of 69%, compared to 73% in patients in the low-risk group. CONCLUSIONS Tumor stage is the best prognostic indicator after radical operation. Inclusion of other tumor- and patient-related variables did not add prognostic information of clinical relevance beyond that provided by tumor stage alone.

Experience with the Impella® recovery axial-flow system for acute heart failure at three cardiothoracic centers in Sweden

Objectives. The Impella® recovery axial-flow system is a mechanical assist system for use in acute heart failure. This retrospective study reports the use of the device at three cardiothoracic units in Sweden. Design. Fifty patients (35 men, mean age 55.8 years, range 26 to 84 years) underwent implantation of 26 Impella®LP 2.5/5.0 (support-time 0.1 to 14 days), 16 Impella®LD (support-time 1 to 7 days) and 8 Impella®RD (support-time 0.1 to 8 days) between 2003 and 2007. Implantation was performed because of postcardiotomy heart failure (surgical group, n=33) or for various states of heart failure in cardiological patients (non-surgical group, n=17). The intention for the treatments was mainly to use the pump as a ”bridge-to-recovery”. Results. Early mortality in the surgical and non-surgical groups was 45% and 23%, respectively. Complications included infection, 36% and right ventricular failure, 28%. Cardiac output and cardiac power output postoperatively were significantly higher among survivors than non-survivors. Conclusions. The Impella® recovery axial-flow system facilitates treatment in acute heart failure. Early intervention in patients with acute heart failure and optimized hemodynamics in the post-implantation period seem to be of importance for long-term survival. Insufficient early response to therapy should urge to consider further treatment options.

Trends in lung cancer incidence in Sweden with special reference to period and birth cohorts

AbstractObjective: Sweden has one of the largest population-based cancer registers in the world that provides an opportunity to examine the trend of lung cancer incidence during a 35-year period. The primary aim of the present study was to estimate the effects of birth cohort, year of diagnosis (period), and age on the time trends of lung cancer incidence rates, and to analyze the gender-specific incidence of different histopathological types of lung cancer. Results: Among men the age-standardized incidence rate increased steadily up to 1982, when a peak of 49 cases per 100,000 person-years was reached. Among women the incidence rate was lower and showed a monotonic increase throughout the observation period. The fastest rate of increase was noted among the youngest women. In women, but not in men, there was a steady increase in risk with each successive birth cohort. For both sexes there were large changes in the histopathological distributions of cases. The most notable was a major increase in adenocarcinomas. Conclusions: The overall age-adjusted incidence rate of lung cancer in Sweden has stabilized in men during the past two decades while rates are still increasing in women. In view of the continued high prevalence of smoking among young women, a future definite increase in the overall number of lung cancer cases in women can be expected.

Venous obstruction and cerebral perfusion during experimental cardiopulmonary bypass

To investigate the effects on cerebral perfusion by experimental venous congestion of the superior vena cava (SVC) during bicaval cardiopulmonary bypass (CPB) at 34 °C, pigs were subjected to SVC obstruction at levels of 75%, 50%, 25% and 0% of baseline SVC flow at two arterial flow levels (low, LQ, high, HQ). The cerebral perfusion was examined with near-infrared spectroscopy (NIRS), cerebral microdialysis and blood gas analysis. SVC obstruction caused significant decreases in the NIRS tissue oxygenation index (TOI) and in SVC oxygen saturations (P<0.05, both groups), while the mixed venous saturation was decreased only in the LQ group. Sagittal sinus venous saturations were measured in the HQ group and found significantly reduced in response to venous congestion (P<0.05). No microdialysis changes were seen at the group level, however, individual ischemic patterns in terms of concomitant venous desaturation, decreased TOI and increased lactate/pyruvate occurred in both groups. The total venous drainage remained stabile throughout the experiment, indicating increased flow in the inferior vena cava cannula. The results indicate that SVC congestion may impair cerebral perfusion especially in the case of compromised arterial flow during CPB. Reduced SVC cannula flow may pass undetected during bicaval CPB, if SVC flow is not specifically monitored.

First known case of Bartonella quintana endocarditis in Sweden

In this report, we present the first known case of Bartonella endocarditis in Sweden. IgG antibody titres to Bartonella spp. were elevated but blood cultures remained negative. Sequencing of a gltA fragment from DNA extracted from heart valve tissue specimens revealed sequence homology with B. quintana.

Selective antegrade cerebral perfusion at two different temperatures compared to hypothermic circulatory arrest – an experimental study in the pig with microdialysis

Hypothermic arrest and selective antegrade cerebral perfusion (SACP) is widely used during aortic arch surgery. The microdialysis technique monitors biomarkers of cellular metabolism and cellular integrity over time. In this study, the cerebral changes during hypothermic circulatory arrest (HCA) at 20 degrees C and HCA with SACP at two different temperatures, 20 and 28 degrees C, were monitored. Twenty-three pigs were divided into three groups. A microdialysis probe was fixated into the forebrain. Circulatory arrest started at a brain and body temperature of 20 degrees C or 28 degrees C. Arrest with/without cerebral perfusion (flow 10 ml/kg, max carotid artery pressure 70 mmHg) lasted for 80 min followed by reperfusion and rewarming during 40 min and an observation period of 120 min. The microdialysis markers were registered at six time-points. The lactate/pyruvate ratio (L/P ratio) and the lactate/glucose ratio (L/G ratio) increased significantly (P<0.05), during arrest, in the HCA group. The largest increase of glycerol was found in the group with tepid cerebral perfusion (28 degrees C) and the HCA group (P<0.05). This study supports the use of SACP over arrest. It also suggests that cerebral metabolism and cellular membrane integrity may be better preserved with SACP at 20 degrees C compared to 28 degrees C.