Background: Immunocompromised patients, particularly after lung transplantation, are at high risk to develop atypical forms of pulmonary infections including influenza A/H1N1. Acute Fibrinous and Organizing Pneumonia (AFOP) is a special histological pattern in acute respiratory failure with high mortality. Case presentation: We describe a 66-year-old woman with double lung transplantation in August 2009 due to end stage pulmonary fibrosis. After prolonged weaning and subsequent promising course, she developed atypical pneumonia with diffuse pulmonary infiltrates in both lungs in January 2010. Infection with influenza A/H1N1 virus was verified. The patient rapidly suffered from respiratory insufficiency and died eight days after this diagnosis. The post-mortem revealed especially in the lower parts of the lungs the classical histological pattern of pure AFOP. Molecular analyses of lung tissue were positive for influenza A/H1N1. Conclusion: To our knowledge we present the first case of AFOP triggered by viral infection, here proven to be influenza virus A/H1N1. Thus, also in the setting of viral infection the highly deadly differential diagnosis of AFOP must be considered.

CC-chemokine ligand 18 (CCL18) is mainly expressed by alternatively activated macrophages and DCs and plays an important role in lung fibrosis, arthritis and other diseases. Here CCL18 was measured in sera of 31 healthy volunteers and 170 patients with lung cancer and correlated these data with histology, tumor stage and clinical parameters. Mean CCL18 serum level of the patients with non-small-cell lung cancer was 150(857) ng/ml vs. 32(61) ng/ml in the healthy control group. Patient groups differ significantly according their histology (adenocarcinoma 143(528) ng/ml vs squamous cell carcinoma 187(857) ng/ml, p<0.02). In addition, we found a significant difference between patients with lower versus higher T-stage (p<0.003). Receiver operating characteristic (ROC) analyses revealed a cutoff point of 83 ng/ml (area under the curve (AUC): 0.968; p<0.0001) to discriminate between healthy controls and non-small-cell lung cancer patients. ROC analyses to discriminate between patients, who died because of cancer related death and those who died for other reasons did not lead to a valid AUC. To stratify the tumor patients, a criterion value plot was performed leading to a point of equal sensitivity and specificity (54%) of 162 ng/ml. Patients with a CCL18 serum level higher than 160 ng/ml had a mean survival time of 623 days. In contrast, those in patients with a baseline level between 83 ng/ml and 160 ng/ml the mean survival time was 984 days (p<0.005). Survival-analysis revealed in adenocarcinoma a mean survival of 1152 days in the group below 83 ng/ml. In the median group the mean survival time was 788 days and in the group with the highest levels the mean survival time was 388 days (p<0.001). In contrast, we found no correlation between the FEV1 and the CCL18 baseline level. In conclusion, in patients suffering from adenocarcinoma increased serum CCL18 levels predict a diminished survival time.

Background: The effect of pleurectomy/decortication or extrapleural pleuropneumonectomy on pulmonary function has not yet been evaluated. The aim of this study was to determine the parameters of pulmonary function before and after pleurectomy/decortication or extrapleural pleuropneumonectomy. Methods: We conducted a review of 48 patients with unilateral malignant pleural mesothelioma who underwent pleurectomy/decortication or extrapleural pleuropneumonectomy. Data including medical history, histology, survival, and pre- and postoperative pulmonary function were extracted from the medical database of the University Medical Center Freiburg, or sought by telephone interview with the general practitioner or patients. Results: 25 patients underwent extrapleural pleuropneumonectomy and 23 had pleurectomy/decortication. Pulmonary function was not significantly reduced in the pleurectomy/decortication group postoperatively. In the extrapleural pleuropneumonectomy group, the median preoperative total lung capacity of 4.8 L (77.7%) differed significantly from the postoperative total lung capacity of 3.5 L (55.3%; p < 0.0006). The median vital capacity was significantly reduced from 2.8 L (77.7%) preoperatively to 1.8 L (47.6%) postoperatively (p < 0.0002). Other parameters were also highly significantly reduced after extrapleural pleuropneumonectomy. Conclusions: Pleurectomy/decortication preserved good pulmonary function, whereas extrapleural pleuropneumonectomy significantly reduced pulmonary function, which may lead to dyspnea and influence the quality of life of these patients.

Histological subclassification of non-small cell lung cancer (NSCLC) has growing therapeutic impact. In advanced cancer stages tissue specimens are usually bioptically collected. These small samples are of extraordinary value since molecular analyses are gaining importance for targeted therapies. We therefore studied the feasibility, diagnostic accuracy, economic and prognostic effects of a tissue sparing simultaneous multi-antibody assay for subclassification of NSCLC. Of 265 NSCLC patients tissue multi arrays (TMA) were constructed to simulate biopsy samples. TMAs were stained by a simultaneous bi-color multi-antibody assay consisting of TTF1, Vimentin, p63 and neuroendocrine markers (CD56, chromogranin A, synaptophysin). Classification was based mainly on the current proposal of the IASLC with a hierarchical decision tree for subclassification into adenocarcinoma (LAC), squamous cell carcinoma (SCC), large cell neuroendocrine carcinoma (LCNEC) and NSCLC not otherwise specified. Investigation of tumor heterogeneity showed an explicit lower variation for immunohistochemical analyses compared to conventional classification. Furthermore, survival analysis of our combined immunohistochemical classification revealed distinct separation of each entity's survival curve. This was statistically significant for therapeutically important subgroups (p = 0.045). As morphological and molecular cancer testing is emerging, our multi-antibody assay in combination with standardized classification delivers accurate and reliable separation of histomorphological diagnoses. Additionally, it permits clinically relevant subtyping of NSCLC including LCNEC. Our multi-antibody assay may therefore be of special value, especially in diagnosing small biopsies. It futher delivers substantial prognostic information with therapeutic consequences. Integration of immunohistochemical subtyping including investigation of neuroendocrine differentiation into standard histopathological classification of NSCLC must, therefore, be considered.

The prognosis of metastatic non-small cell lung cancer (NSCLC) is poor, and platinum-based chemotherapy improves the median survival for only a few months. A subgroup of patients with oligometastatic disease may benefit from surgical resection, but only very limited data are available to date. We conducted a retrospective review of all patients with synchronous extrapulmonary oligometastatic NSCLC undergoing surgical resection in our department. Data regarding medical history, histology, number of metastases, and survival status were extracted from the medical database of the University Medical Center, Freiburg. Fifty-six patients underwent surgical resection for oligometastatic lung cancer. Five patients were lost during follow-up and therefore censored. One patient died perioperatively due to acute respiratory distress syndrome. The remaining 50 patients had an overall median survival time of 14.6 months. Analyzing the influence of metastatic site, we found a median overall survival of 23.4 months for patients with soft tissue metastasis, 16.7 months for patients with brain metastasis, 9.5 months for patients with adrenal gland involvement, and only 4.3 months for patients with bone metastasis (p < 0.005). Upon multivariate analysis, bone metastasis was the only significant parameter influencing median overall survival (p < 0.004). Based on our data, we conclude that an aggressive surgical approach for oligometastatic NSCLC can be performed with acceptable mortality and morbidity. In this rare constellation, surgical therapy may be an option in selected cases.