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Background and objectives It is unclear how much additional perioperative risk a sleeve lobectomy could pose in comparison to lobectomy. The objective of this analysis was to compare the complication rate, 30-day mortality, and overall survival between lobectomy and sleeve lobectomy without prior neoadjuvant treatment in non-small-cell lung cancer (NSCLC). Methods This is a retrospective study using our prospective database for quality assurance in our hospital. Inclusion criteria for our study was a completed lobectomy or sleeve lobectomy for primary treatment of NSCLC. Results In 506 patients, the tumor was treated by means of standard lobectomy. In 252 patients with central tumor localization, sleeve lobectomy was performed. Postoperative complications occurred in n:148 (29.24%) patients of the lobectomy group and in n = 76 (30.15%) of the sleeve group. The mortality rate difference between the two groups was statistically significant and favored the lobectomy group (0.78% vs. 4.76%, p = .007). Five year survival was 69.97% for the lobectomy and 65.59% for the sleeve group (p = .829). Conclusion Sleeve lobectomy for primary surgical treatment of NSCLC has comparable perioperative complications with lobectomy. Sleeve lobectomy does not seem to negatively influence survival. Postoperative mortality was higher in the sleeve group.

Prevention of bronchial complications after airway surgery must be our primary goal. Understanding bronchial and anastomotic healing is the first step to success. This can be improved by standardizing operating technique (bronchial closure and end-to-end anastomosis) as well as postoperative care. Bronchopleural fistula after pneumonectomy still remains a feared complication with a high mortality rate. Especially after sleeve resection interpretation of endobronchial healing and postoperative measures of care with the help of an algorithm, may avoid anastomotic insufficiency and therefore reduced the secondary pneumonectomy rate.

Introduction Sleeve resection is an established oncological operative treatment for centrally located tumors with reduced complications compared to pneumonectomy. In cases of neoadjuvant chemoradiotherapy, the optimal timing of surgery for bronchial anastomotic healing has not been adequately explored. Materials and methods Between 2006 and 2017, 584 tracheobronchial sleeve resections were retrospectively analyzed. We selected all patients (n = 88) after sleeve lobectomy or sleeve bilobectomy for lung cancer with fully completed neoadjuvant chemoradiotherapy. Bronchial healing was assessed by bronchoscopy on the 7th postoperative day using our earlier published classification from grades 1 to 5. Results The median interval to surgery was 50 days (interquartile range 46-53, mean 50.03 ± 3.72). Mean anastomotic grade was 2.05 ± 1.03 and in 29.5% of the patients a critical anastomosis (grade ≥3) was documented. Anastomotic healing showed optimal results (bronchoscopic grade mean value: 1.5 ± 0.70) between the 6th and 8th postchemoradiotherapy week (P = .001). All patients operated before (bronchoscopic grade mean value: 2.3 ± 1.02) or after the above period (bronchoscopic grade mean value: 2.5 ± 1.15) had an increased ratio of anastomotic healing complications. Conclusion It is safer to perform sleeve-resections for non-small cell lung cancer after neoadjuvant trimodal treatment between the 6th and 8th week of completion of chemoradiotherapy.

Background Preoperative radiotherapy and/or chemotherapy of lung cancer in patients with locally advanced disease is an option in multimodal treatment. Sleeve lobectomy has an important part in decreasing complications and sparing lung function. We present our experience in a large cohort of patients after sleeve lobectomy with or without neoadjuvant treatment and standardized assessment of bronchial anastomotic healing. Methods The data used for this study were collected in a prospective database in our hospital. Anastomotic healing was documented by bronchoscopy on the seventh postoperative day and thereafter only when necessary, using a standardized scoring system. From 2006 to 2017, we performed 501 sleeve lobectomies representing 19% of all lung cancer resections. A total of 365 of patients had no preoperative treatment (73%), 41 had neoadjuvant chemotherapy (8%), and 95 had radiochemotherapy (19%). Results Using our scoring system of the bronchial anastomosis from 1 (excellent) to 5 (insufficient), we found the anastomosis was worse than grade 2 after no treatment, chemotherapy, or radiochemotherapy in 17%, 10%, and 30%, respectively (P = .002). The rate of anastomotic insufficiency was equally low after no pretreatment and chemotherapy (2.7% and 2.4%) and rose to 10.4% after radiotherapy (P = .002). Similarly, the risk for pulmonary complications was higher after radiochemotherapy (39%) compared with no pretreatment (29%) or chemotherapy (27%), respectively (P = .382). Conclusions Neoadjuvant radiotherapy is associated with worse wound healing of the anastomosis after sleeve lobectomy in lung cancer. There seems to be a higher risk for anastomotic insufficiency and complications.

The therapy of severely injured patients is demanding and promising only in an interdisciplinary context. From a thoracic surgical perspective, the blunt chest trauma is in the foreground; as it is the 2nd leading cause of death after traumatic brain injury. The first step is to identify the potentially life-threatening injury and its treatment (airway obstruction, prevention of gas exchange, tension pneumothorax, serious bleeding complications in lung-/vascular injuries). Pneumothorax or tension pneumothorax is present in 20% of all polytrauma patients and 50% of all patients with severe chest trauma. In most cases, the use of a chest tube is sufficient in the acute phase (90%). For complex injuries with persistent thoracic haemorrhage and haemodynamic instability of the patient or pleural fistulization with increasing skin emphysema, surgical treatment should be performed at an early interval. Nevertheless, emergency thoracotomy is rarely required at this early stage.

Background: The aim of this study was to compare the perioperative outcome of patients receiving anatomic segmentectomy either by open surgery or video-assisted thoracoscopic surgery (VATS). To assess the short-term morbidity of the procedure itself, lung cancer patients in all stages as well as patients with pulmonary metastases and benign lesions scheduled for segmental resection were enrolled in this study. Methods: A retrospective analysis of prospectively collected data on 445 consecutive patients that underwent segmentectomy either by VATS (n=233) or thoracotomy (n=212) was performed. A propensity-matched analysis was conducted based on age, gender, smoking history, histology, tumor size, forced expiratory volume in 1 second (FEV1) and history of previous pulmonary resections. The matched sample included two groups of 140 patients each. Results: Both study groups were comparable with respect to age, gender, smoking history, diagnosis, tumor size, pulmonary function and history of previous pulmonary resections. VATS segmentectomy was associated with decreased length of stay (7.4 vs . 9.5 days, P vs . 5.9 days, P=0.012) and severe postoperative complications (1.4% vs . 7.1%, P=0.018). Conclusions: VATS segmentectomy is safe and effective for the treatment of benign and malignant pulmonary lesions. Compared with open thoracotomy, it is associated with shorter hospitalization time and decreased number of severe complications. The preservation of functional lung tissue, combined with a minimally invasive approach, make VATS segmentectomy highly suitable for patients with reduced pulmonary function or severe comorbidities.

Trauma is the leading cause of death worldwide. Approximately 2/3 of the patients have a chest trauma with varying severity from a simple rib fracture to penetrating injury of the heart or tracheobronchial disruption. Blunt chest trauma is most common with 90% incidence, of which less than 10% require surgical intervention of any kind. Mortality is second highest after head injury, which underlines the importance of initial management. Many of these deaths can be prevented by prompt diagnosis and treatment. What is the role of the thoracic surgeon in the management of chest trauma in severely injured patients? When should the thoracic surgeon be involved? Is there a place for minimal invasive surgery in the management of severely injured patients? With two case reports we would like to demonstrate how the very specific knowledge of thoracic surgeons could help in the care of trauma patients.

Das nicht-kleinzellige Lungenkarzinom ist eine der haufigsten Krebserkrankungen weltweit und damit auch eine der haufigsten krebsbedingten Todesursachen. Bei Erstdiagnose haben bereits rund 40 % aller Patienten Fernmetastasen (Tumorstadium UICC IV) und werden mit einer palliativen systemischen Chemotherapie und/oder Tyrosinkinase-Inhibition behandelt. Eine kleine Gruppe dieser Patienten weist jedoch nur eine einzige Fernmetastase auf. Diese kann synchron oder erst metachron auftreten und intrathorakal oder extrathorakal liegen. Im Gegensatz zu multiplen Metastasen, die Ausdruck einer diffusen systemischen Erkrankung sind und dementsprechend einer systemischen Therapie bedurfen, kann man das Auftreten singularer Metastasen als noch begrenzte Erkrankung auffassen. Durch lokale Exzision der Metastasen und des Primartumors haben die Patienten eine Chance auf Heilung. Eine Resektion des Primartumors und der singularen Metastase kann die Uberlebenswahrscheinlichkeit in vielen Fallen deutlich verbessern.

Introduction The aim of this study was to determine whether preoperative elevated serum C-reactive protein (CRP) is an independent risk factor of postoperative morbidity and mortality after pulmonary resection for lung cancer. Material and methods A retrospective analysis of prospectively collected data on 1414 consecutive patients that underwent an anatomic resection for lung cancer was performed. Patients’ characteristics, operative procedures and the postoperative outcome were assessed with a standardised data entry form. Univariate and multivariate analyses were conducted to identify factors that affect morbidity and mortality. Results Postoperative complications occurred in 35.5% of the patients. The mortality rate was 3.2%. Patients with preoperative C-reactive protein above 40 mg/l showed more overall complications and a higher mortality than patients below this limit. Patients with a CRP level between 3 mg/l and 40 mg/l had no significant increase in morbidity and mortality compared to patients with values ​​below the detection limit ( Conclusions Preoperative serum C-reactive protein level is an independent and significant indicator for elevated morbidity and mortality after pulmonary resection. We propose the evaluation of CRP levels as a preoperative diagnostic modality of risk assessment in addition to standardised functional testing.

Introduction: Phospatidylinositol-3-kinases (PI3K) play an important role in various cell processes. Oncogenic mutations in the PIK3CA gene, which codes for the catalytic subunit, have been identified in various malignancies and activate the PI3K/AKT/mTOR pathway, which is a critical driver of tumorigenesis. Methods: We tested 41 tumor samples with known KRAS, BRAF, and EGFR mutation status for the occurrence of mutations in the PIK3CA gene, using a pyrosequencing assay. Results: Pyrosequencing revealed 2 mutations (4.9%) in the PIK3CA gene, one in exon 9 and the other in exon 20. Both mutations have not been identified yet in lung tumor tissue. Discussion: The screening of our small patient cohort by pyrosequencing identified 2 mutations (4.9%) in PIK3CA, one in exon 9 (Q546H) and the other in exon 20 (M1043T). Both mutations have not been described in lung tumors yet and seem to be rather uncommon mutations. Future screening of large patient cohorts with pyrosequencing may contribute to the detection of more mutations in lung cancer because of the low limit of detections of this method and may contribute to a better understanding of the interaction of mutations and tumorigenesis.

Background: Thoracotomy leads to chronic neuropathic pain in up to 50% of patients and is responsible for an impaired quality of life. Intercostal nerve injury has been suggested to be responsible for this pain. In the present study the impact of paravertebral intercostal neurectomy on post thoracotomy pain was assessed. Methods: In this single center parallel-group randomized controlled trial patients underwent muscle sparing anterolateral thoracotomy and anatomical lung resection for lung cancer. A subcostal approach was used for thoracotomy with single paravertebral neurectomy being performed at the beginning of the procedure at the level of the retracted intercostal space. For documentation of neuropathic pain the Leeds Assessment Score for Neuropathic Symptoms and Signs (LANSS) was used postoperatively. The primary endpoint was defined as LANSS ≥12 points on day 120. In addition, the numeric pain rating scale (NRS) was used to score pain intensity. Results: Out of 172 patients initially randomized 161 patients were investigated following intraoperative and postoperative drop-out criteria. All patients required anatomical lung resection via thoracotomy. Five patients were lost for follow up. For the remaining 156 patients there was no difference between the two groups with regard to LANSS ≥12: 26.6 % in patients with neurectomy and 28.8% in control-subjects (P=0.78). In addition, the NSR score at day 120 did not differ significantly at rest and during activity between the two groups (at rest: 21.7% vs . 15.8% P=0.439; activity: 24.5% vs . 21.9% P=0.735). Conclusions: Neurectomy was not shown to reduce the post thoracotomy pain syndrome in patients with anatomical lung resection following anterolateral muscle sparing thoracotomy.

Objective Ischemia and infection of the distal part of the tracheobronchial anastomosis are the leading causes of bronchial anastomotic leakage with a high morbidity and mortality. To improve interpretation of healing of the anastomosis and the consequences, we have developed a classification scheme that allows quality control and defines early and standardized treatment of complications. Patients and Method We conducted a retrospective analysis of the records of 202 patients treated in our institution between January 1, 2006 and December 31, 2010 after sleeve lobectomy. All patients received prophylactic inhalation with tobramycin 80 mg twice a day. Neoadjuvant treatment was given in 21% of the patients. Routine bronchoscopy on day 7 was performed with classification of the anastomosis as follows: X, unknown; 1, healing well with no fibrin deposits; 2, focal fibrin deposits and superficial (mucosal) necrosis; 3, circular fibrin deposits, superficial (mucosal) necrosis, and/or ischemia of the distal mucosa; 4, transmural necrosis with instability of the anastomosis; and 5, perforation, necrosis of the anastomosis, and insufficiency. Results The anastomosis was graded as satisfactory (1 and 2) in 86% of the patients. In 14%, it was regarded as critical (≥3-5) leading to systemic antibiotic treatment and control bronchoscopy. The overall 30-day mortality was 1%. Conclusions Quality control of the tracheobronchial anastomosis comprised bronchoscopy performed before patients were dismissed. Inasmuch As postoperative bronchoscopy is not always performed by the operating surgeon, this classification is an aid to improve the description of endobronchial healing and to commence treatment of critical bronchial healing.

BACKGROUND: In this study the histological examination of pulmonary nodules and a comparison of the number of pre-, intra- and post-operative lung metastases in patients with a previous history of malignant disease were assessed. PATIENTS AND METHODS: Between 1998 and 2003 we operated on 276 patients with suspected lung metastases. The histology of the primary tumour, the number of preoperatively diagnosed nodules, the number of lesions removed during surgery and the number of histologically confirmed metastases of 276 patients are presented. RESULTS: In 276 patients a resection was performed. 161 of the patients were men (58.1 %). The median age was 62 years (range: 21 - 86 years). In 110 cases a left-sided thoracotomy was performed (39.8 %), in another 110 cases a right-sided thoracotomy was performed and in 56 cases we perfomed a bilateral thoracotomy (20.4 %). In 15.2 % the histology of the resected nodules was benign. In 8.6 % of the cases the histological examination showed a primary lung cancer in stage I, in 74.4 % of the cases the histology confirmed a metastasis of the primary cancer. CONCLUSIONS: Solitary pulmonary nodules in patients with a previous history of malignant disease should always be resected for histological examination. Multiple pulmonary nodules should be histologically reappraised if there is any doubt about the entity.

When a lung tumor arises in segment 6, the close anatomical relationship to the middle lobe bronchus may make a lower bilobectomy necessary. Sleeve lobectomy may be an alternative. These procedures were compared retrospectively in 36 patients operated on between January 2005 and December 2006 with non-small-cell lung cancer (stage I-IIIB) of the right lower lobe. Sleeve lobectomy was performed in 21 patients and bilobectomy in 15 (41%). Preoperative lung function was comparable in both groups. Radical resection was achieved in 34/36 patients. Operation time was 121 min for sleeve lobectomy and 144 min for bilobectomy. Chest tubes were removed after 5 days in both groups. Postoperative lung function was better after sleeve lobectomy than bilobectomy (forced expiratory volume in 1st sec: 78% vs. 69%). Preservation of the middle lobe by sleeve lobectomy is feasible. There was no evidence that this resection was less radical, and complication rates were similar in both groups.

Objective. In diffuse parenchymal lung diseases, the evolution of pulmonary fibrosis is often devastating and may result in death. In this study the role of CCL18 as a biomarker of disease activity in idiopathic interstitial pneumonias (IIPs) and systemic sclerosis (SSc) with lung involvement was evaluated. Methods. CCL18 was assessed in supernatants of cultured bronchoalveolar lavage (BAL) cells as well as BAL fluid and serum samples from 43 patients with IIPs, 12 patients with SSc, and 23 healthy control subjects. Concentrations of CCL18 were measured by enzyme-linked immunosorbent assay, and expression of CCL18 was assessed by flow cytometry. Results. CCL18 concentrations were statistically significantly increased in all patients with fibrotic lung diseases. Spontaneous CCL18 production by BAL cells was negatively correlated with total lung capacity and the diffusion capacity for carbon monoxide, whereas there was a positive correlation of CCL18 concentrations with BAL neutrophil and eosinophil cell counts. Flow cytometry revealed an increase in the percentage of CCL18-positive alveolar macrophages and an increase in the CCL18 fluorescence intensity per cell in patients with fibrotic lung diseases. In a cohort of patients who were followed up for at least 6 months (n 40), a close negative correlation was observed between changes in the predicted total lung capacity and changes in CCL18 serum concentrations. Conclusion. These findings suggest that CCL18 production by BAL cells and serum CCL18 concentrations reflect pulmonary fibrotic activity in patients with IIPs and those with SSc. Monitoring changes in CCL18 production might be an extraordinarily useful tool in clinical practice and in studies aimed at evaluating new approaches for treatment of fibrotic lung diseases.

Introduction Spontaneous regression of cancer is defined as a complete or partial, temporary or permanent disappearance of tumor in the absence of specific therapy. With only a few cases reported, spontaneous regression is extremely rare in primary lung cancer. Regarding spontaneous regression in lung cancer, recent investigations revealed the role of immunological mechanisms, thus indicating potential treatment options by specific immunotherapy in the future. Case presentation A 76-year-old Caucasian man with progressive dyspnea presented to our hospital. A computed tomography scan revealed a tumor mass in the upper lobe of his right lung and enlarged mediastinal lymph nodes. A biopsy of a paratracheal lymph node by mediastinoscopy disclosed metastatic lung cancer. By immunohistochemical findings the tumor was classified as large cell carcinoma. Diagnosed with clinical stage IIIA non-small cell lung cancer, a neoadjuvant therapy concept was indicated. However, before starting chemoradiation, a computed tomography scan showed a regression of both the tumor mass in the upper lobe of his right lung and the mediastinal lymphadenopathy. As a repeated computed tomography scan showed further regression, we agreed with our patient to perform routine follow-up instead of starting therapy. To date, no relapse has been reported. Conclusions Given the circumstances that regression started after the biopsy and involved both the tumor in the upper lobe of his right lung and the mediastinal lymph node metastases, an immune response is a reasonable explanation for the observed spontaneous regression in this case.

EGFR mutations were previously found in patients suffering from peritoneal mesothelioma but have not yet been described in pleural mesothelioma. The aim of the present study was the identification of EGFR mutations in patients suffering from pleural mesothelioma. Pleural mesothelioma tissue from 31 patients was used to analyze possible mutations in the EGFR gene comprising the exons 18-21 with the codons 719, 768, 790, 858 + 861, 731 + 734, 785, 797 + 801, 831, and 868 with pyro-sequencing. The results indicate that 31 pleural mesothelioma patients show a wild-type EGFR gene when analyzing the codons D19, 768, 790, 858 + 861, 731 + 734, 785, 797 + 801, 831, and 868, whereas 2 patients have a mutation in the EGFR gene in codon 719. Sanger sequencing of the EGFR codon 785 was used for the determination of a polymorphism in the sequencing of tumor-free patients and pleural mesothelioma patients with a distribution of a wild-type homozygous sequence with guanine, a wild-type heterozygous sequence having guanine and adenine, a wild-type homozygous sequence with adenine, and a wild-type heterozygous sequence with adenine and guanine. Next, the identification of less EGFR mutations in the EGFR gene of the pleural mesothelioma an up to this time unknown polymorphism in the EGFR gene was identified which could be wrongly interpreted as a mutation.

Lung cancer remains one of the leading causes of cancer-related death in developed countries. Although lung adenocarcinomas with EGFR mutations or EML4-ALK fusions respond to treatment by epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) inhibition, respectively, squamous cell lung cancer currently lacks therapeutically exploitable genetic alterations. We conducted a systematic search in a set of 232 lung cancer specimens for genetic alterations that were therapeutically amenable and then performed high-resolution gene copy number analyses. We identified frequent and focal fibroblast growth factor receptor 1 (FGFR1) amplification in squamous cell lung cancer (n = 155), but not in other lung cancer subtypes, and, by fluorescence in situ hybridization, confirmed the presence of FGFR1 amplifications in an independent cohort of squamous cell lung cancer samples (22% of cases). Using cell-based screening with the FGFR inhibitor PD173074 in a large (n = 83) panel of lung cancer cell lines, we demonstrated that this compound inhibited growth and induced apoptosis specifically in those lung cancer cells carrying amplified FGFR1. We validated the FGFR1 dependence of FGFR1-amplified cell lines by FGFR1 knockdown and by ectopic expression of an FGFR1-resistant allele (FGFR1(V561M)), which rescued FGFR1-amplified cells from PD173074-mediated cytotoxicity. Finally, we showed that inhibition of FGFR1 with a small molecule led to significant tumor shrinkage in vivo. Thus, focal FGFR1 amplification is common in squamous cell lung cancer and associated with tumor growth and survival, suggesting that FGFR inhibitors may be a viable therapeutic option in this cohort of patients.

ABSTRACT: A total of three cases with novel constellations regarding mutation patterns in non-small-cell lung cancer (NSCLC) are reported. The mutation patterns that are observed are novel and unexpected. First, a combined simultaneous KRAS mutation and EML4–ALK translocation, both in the main tumor and a bone metastasis, were observed, these mutations are assumed to mutually exclude each other. A further two cases include a father and a daughter, both of whom are suffering from NSCLC with different EGFR mutation patterns. A common cause was assumed; however, could not be deduced to mutations in the KRAS, BRAF and EGFR genes. The aforementioned cases are important, as it must be taken into account that mutations previously assumed to be exclusive can occur in combination, may influence the clinical outcome and may require different therapy compared with single mutated tumors. It has to be discussed whether diagnostic algorithms need to be adapted. The cases of father and daughter show that further unknown factors can influence development of NSCLC.

to the bronchial system Alberto Lopez-Pastorini*, Till Plones, Corinna Ludwig and Erich Stoelben Department of Thoracic Surgery, University Medical Center Witten/Herdecke, Lung Clinic Merheim, Campus Cologne, Germany * Corresponding author. Department of Thoracic Surgery, University Medical Center Witten/Herdecke, Lung Clinic Merheim, Campus Cologne, Ostmerheimerstr. 200, 51109 Cologne, Germany. Tel: +49-221-89078640; fax: +49-221-89073048; e-mail: lopeza@kliniken-koeln.de; albvalelopez@yahoo.de (A. Lopez-Pastorini). Received 11 September 2013; accepted 16 October 2013

Benign stenosis of trachea results mainly from tracheotomy, ventilation, or trauma. The combination of a defect of the mucosa or the tracheal wall and infection produce secondary scar tissue healing with shrinkage of the tracheal lumen or instability of the tracheal wall. Standard of treatment consists of resection of the pathologic segment of the trachea with end-to-end anastomosis. In case of involvement of the larynx, partial resections of the anterior cricoid cartilage or division of the larynx with tracheolaryngeal silicone stents are used. Short-term and long-term results are satisfying considering some technical recommendations.

A 31-year old female with left-sided pneumonia was admitted to a district hospital due to progressive dyspnoea. She underwent endotracheal intubation and received a central venous catheter (CVC) via the V. subclavia sinistra. However, chest X-ray showed malposition of the CVC and computed tomography confirmed left-sided serothorax and direct lung puncture of the CVC with its tip in the upper pulmonary vein. The patient was transferred to our hospital. After admission, video-assisted thoracoscopy was performed for removal of the CVC and left-sided pleural decortication. Postoperatively, the patient was transferred to the intensive care unit. Adequate antibiotic therapy led to resolution of the pneumonia, and the patient was transferred to the normal ward one week after surgery. The further course was uneventful and the patient was discharged home on day 14.

Aim: To compare the number of lung metastases seen preoperatively on computed tomography in patients with a previous history of malignant disease with the number of resected pulmonary nodules and the number of histologically proven lung metastases. Patients and methods: Between 1998 and 2003, we operated on 281 patients with suspected lung metastases. The histology of the primary tumour, the number of preoperatively diagnosed nodules, the number of lesions removed during surgery and the number of histologically confirmed metastases of 276 patients are presented. Results: Resection of lung metastases was performed in 276 patients. The median age was 62 years (21—86 years). The mean number of nodules seen on the CT scan was 1.9 (total: 515 nodules), 2.9 pulmonary lesions were removed (total: 835 nodules) and 2.1 nodules were confirmed as lung metastases (total: 560). In 39%, the number of lesions found and removed during the operation was higher than counted on the preoperative CTscan. These extra nodules found during the operation were confirmed as lung metastases in 16% of all patients. A benign solitary lesion was found in 15.2% of the patients and in 7.9% a primary carcinoma of the lung was diagnosed. In patients with a solitary nodule we found no metastasis in 16.4%, one lung metastasis in 76.7% and more than one lung metastasis in 6.9%. In patients with more than one nodule on the preoperative CTscan, an identical number of lung metastases were histologically confirmed in 35% of the patients, a larger number in 27.4% and a smaller number in 37.6%. Conclusions: In patients with a previous history of malignant disease, 15.2% of the pulmonary lesions are benign. Video-assisted thoracoscopic surgery (VATS) is a safe diagnostic and therapeutic method for solitary lesions, with little discomfort for the patient. In patients with more than one nodule on the CT scan, manual exploration of the lung is necessary to detect further lesions. # 2007 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

We characterized genome alterations in 1255 clinically annotated lung tumors of all histological subgroups to identify genetically defined and clinically relevant subtypes. More than 55% of all cases had at least one oncogenic genome alteration potentially amenable to specific therapeutic intervention, including several personalized treatment approaches that are already in clinical evaluation. Marked differences in the pattern of genomic alterations existed between and within histological subtypes, thus challenging the original histomorphological diagnosis. Immunohistochemical studies confirmed many of these reassigned subtypes. The reassignment eliminated almost all cases of large cell carcinomas, some of which had therapeutically relevant alterations. Prospective testing of our genomics-based diagnostic algorithm in 5145 lung cancer patients enabled a genome-based diagnosis in 3863 (75%) patients, confirmed the feasibility of rational reassignments of large cell lung cancer, and led to improvement in overall survival in patients with EGFR-mutant or ALK-rearranged cancers. Thus, our findings provide support for broad implementation of genome-based diagnosis of lung cancer.

SummaryLung adenocarcinoma, the most common subtype of non-small cell lung cancer, is responsible for more than 500,000 deaths per year worldwide. Here, we report exome and genome sequences of 183 lung adenocarcinoma tumor/normal DNA pairs. These analyses revealed a mean exonic somatic mutation rate of 12.0 events/megabase and identified the majority of genes previously reported as significantly mutated in lung adenocarcinoma. In addition, we identified statistically recurrent somatic mutations in the splicing factor gene U2AF1 and truncating mutations affecting RBM10 and ARID1A. Analysis of nucleotide context-specific mutation signatures grouped the sample set into distinct clusters that correlated with smoking history and alterations of reported lung adenocarcinoma genes. Whole-genome sequence analysis revealed frequent structural rearrangements, including in-frame exonic alterations within EGFR and SIK2 kinases. The candidate genes identified in this study are attractive targets for biological characterization and therapeutic targeting of lung adenocarcinoma.

Intermittent positive-pressure breathing is thought to avoid atelectasis and improve pulmonary function after major lung resections. Since no clear scientific data was available to confirm this, our objective was to determine whether atelectasis can be avoided and if postoperative lung function is improved. Prospective analysis was carried out in 135 patients operated on between 2007 and 2009; 55 received intermittent positive-pressure breathing. Pre- and postoperative lung function tests were similar in both groups. Pulmonary complications were observed in 19% of patients without intermittent positive-pressure breathing and 27% of those who received this treatment. We were unable to find evidence that additional improvement in postoperative pulmonary function is achieved when adding intermittent positive-pressure breathing to the standard physical therapy.

Lung cancer invasion of the chest wall is not a common challenge and represents only about 5% of all patients resected for lung cancer. In T3N0M0 tumours, long-term survival reaches 40-50%, provided certain conditions are fulfilled. The number of explorative thoracotomies and the rate of non-radical resections might be high due to the local extension of an aggressive tumour. Mortality after resection is as high as for pneumonectomy. For historical and anatomical reasons, we have to divide the patients into two groups: infiltration of, and above, the second rib (Pancoast) and tumours located caudally to the second rib. We have to define the two entities. There is a problem concerning correct diagnosis: many tumours reach the chest wall. If the lung is not adherent to the parietal pleura, a standard lobectomy can be performed. However, in the case of adhesions, the differentiation between tumour invasion and inflammation may be difficult. We do not want to perform over-treatment since lung resection en bloc with the chest wall has a higher morbidity and mortality than lobectomy. But we have to avoid opening the tumour intraoperatively or perform a non-radical resection. Therefore, we need a preoperative diagnostic tool answering the question of extrapulmonary infiltration. In this context, we will discuss whether extrapleural lung resection is acceptable in the case of pleural invasion without chest wall involvement. The prognosis of patients with tumours invading the chest wall and mediastinal lymph node metastasis is worse. But patients with ipsilateral supraclavicular lymph node metastasis are not excluded. Thus, careful clinical investigations are necessary. To achieve complete resection, the surgeon should use anatomical knowledge to choose the best form of access to make radical resection more feasible. The problem of pain after thoracotomy is accentuated after chest wall resection, especially after paravertebral resection. The use of modern pain treatment is very important.

Objective: In a previous experimental study on 60 freshly slaughtered pig trachea, a statistically significant better resistance to pressure was found after mechanical stapling compared to hand suture. The objective of this study was to determine the resistance to pressure of a bronchial stump depending upon the closure technique (manual vs. mechanical) used in sheep 14 days after pneumonectomy. Methods: Pneumonectomy was performed on 30 sheep, which were alternatively closed either by a double-layer running suture at 908 to the cartilaginous rings or with an automatic stapling device. Exactly 14 days after pneumonectomy, the animals were sacrificed and the trachea with the bronchial stump was retrieved. Sutures were placed under pressure until air leakage was observed. The air-leakage pressure was recorded digitally. Results: In both groups, there was no evidence of a bronchopleural fistula. As in the previous experimental study, mean values of air-leakage pressure revealed a large standard deviation in both groups (min. 0.16–max. 1.15 bar). Unlike the results in the first experiment there was no statistically significant difference between the two groups. Conclusions: After 14 days, when a bronchial stump is considered to be healed, the resistance to pressure of a mechanical suture is equal to that of the manual suture. q 2004 Elsevier B.V. All rights reserved.

Background The advantage of sleeve lobectomy as an alternative to pneumonectomy for preserving lung function is obvious and among other arguments allows operating on patients with lung cancer who would not tolerate pneumonectomy. The purpose of this retrospective, nonrandomized study is to compare the early (30-day mortality) and late (5-year survival) outcomes of both procedures. Methods The charts of 310 patients who underwent either pneumonectomy or sleeve lobectomy for lung cancer stages I to IIIA from 1987 to 1997 were reviewed. One hundred ninety-four patients underwent pneumonectomy, and 116 patients underwent sleeve lobectomy. Specific operative complications, i.e., anastomotic leakage versus stump dehiscence, perioperative complications, 30-day or in-hospital mortality, and 5-year survival were registered for comparison of the immediate risk of the respective procedures. Results In the bronchial sleeve lobectomy group, the incidence of anastomotic leakage was 6.9% (8 of 116 patients) and the operative mortality was 4.3%. The incidence of bronchial stump fistulas after pneumonectomy was 3.6% (7 of 194 patients), and early mortality was 4.6%. All but 6 patients (98%) had a complete resection. Overall 5-year survival after sleeve lobectomy was 39% and after pneumonectomy, 27%. The distribution of 5-year survival stage by stage in either group is presented. Sleeve lobectomy, age younger than 65 years, pN0, and stage I are positive prognostic factors for long-term survival. In the multivariate analysis, pneumonectomy is a negative prognostic factor. Conclusions The indication for pneumonectomy versus sleeve lobectomy depends on the localization of the primary tumor on the one hand, and on cardiorespiratory function, which might be more often distinctly impaired in the sleeve group, on the other hand. This could explain why the mortality in the sleeve lobectomy group was identical with that in the pneumonectomy group. However, both techniques are appropriate treatment modalities of advanced lung cancer or patients with critical functional reserve. Therefore, whenever possible, sleeve lobectomy should be performed.

Publisher Summary This chapter discusses several drugs that act on the immune system. Modified interferon alfa-2b has a similar profile of adverse effects as the unmodified interferon alfa-2b but with more frequent dose-limiting neutropenia. No particular adverse effect has emerged since the use of this new formulation. Chorea is a very rare manifestation of interferon alfa neurotoxicity. Neutropenia is a dose-limiting adverse effect of interferon alfa, particularly in patients with chronic hepatitis C and cirrhosis. Cutaneous necrosis at injection sites has been commonly reported with interferon alfa and has also been described with pegylated interferon alfa-2b. In the latter case, the lesions are healed under local therapy and the same dose of interferon is maintained. Extensive oral pemphigus due to interferon alfa has rarely been reported. The chapter discusses a case study wherein the differential effects of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) on several coagulation parameters have been compared in 34 patients who received the colony-stimulating factors after bone-marrow transplantation. The data suggested the activation of the coagulation system in patients treated with GM-CSF, which resulted in it tendency to more frequent veno-occlusive disease of the liver and a significantly higher incidence of hemorrhage. Dacluzumab is a humanized antibody directed against the alpha chain of the IL2 receptor. The adverse events of this include infectious complications during treatment with a high incidence of cytomegalovirus reactivation.

Postoperative mortality rates have been published in relation to operative procedure or preexisting pulmonary and extrapulmonary diseases. We analyzed our patients for the effect of the postoperative tumor stage on perioperative mortality.Retrospective study of all thoracotomies for resections ( n=1281) in primary lung cancer from January 1987 to December 1997. Uni- and multivariate analysis was performed for operative procedure, mortality (30 and 90 days), tumor stage, sex, age, tumor localization, and completeness of resection. Radical resection was achieved in 91.9% of the patients.Overall postoperative deaths occurred in 4% and 7.3% of patients after 30 and 90 days respectively. Depending on the operative procedure the mortality after segmental resection ( n=116) was 0.9% and 1.7%, lobectomy ( n=621) 3.0% and 5.7%, sleeve lobectomy ( n=152) 5.3% and 7.9%, and pneumonectomy ( n=314) 6.7% and 12.5%, respectively. Within 30 and 90 days postoperatively deaths occurred, respectively, in 0.8% and 1.0% of stage I patients ( n=493), 5.4% and 5.4% of stage II ( n=147), 4.9% and 8.8% of stage IIIa ( n=388), 7.2% and 16.6% of stage IIIb ( n=148), 8.9% and 20.5% and of stage IV ( n=114). Multivariate analysis showed postoperative tumor stage to be the factor most closely related to within the first 90 days.Tumor stage but not type of resection is the strongest predictor of postoperative mortality in these subpopulations.

e18505 Background: Adjuvant chemotherapy is the standard treatment for early stage non-small-cell lung cancer (NSCLC) patients after complete resection. The most evidence-based data exist for the c...

To assess the relationship between postoperative infective complications and the CD4 count.Retrospective and biometric study.Two university hospitals, Switzerland.40 HIV-positive patients who had had CD4 counts done during the three months before operation.Clean and contaminated gastrointestinal and orthopaedic procedures.Postoperative infective complications.15 patients developed postoperative infective complications (38%), 6 of which (40%) were HIV-related. CD4 cell count, as well as the type of operation (contaminated or clean), influenced the infective complication rate. The risk of infective complications after a contaminated procedure when the CD4 count was below 200 mm3 was more than 50%. In clean operations, even when the CD4 cell count was close to 0, the rate of infective complications was never as high as 50%. Patients with a CD4 cell count of 500 or more have a similar rate of infective complications as HIV seronegative patients.Indications for operation in HIV-positive patients must take into account the CD4 cell count and the type of operation.

Rubber band ligation is a well established treatment of internal second-degree hemorrhoids. Up to now, the long-term results (> 5 years) of this method have not been assessed. The aim of this study was to determine the long-term success rate of rubber band ligation in patients with a first episode of second-degree hemorrhoids not responding to medical treatment (local cream with laxative). A total of 92 patients who were treated between 1979 and 1997 for second-degree hemorrhoids responded to a questionnaire. The need for complementary conservative (sclerotherapy, cryotherapy or rubber band ligation) or surgical treatment was considered indicative of relapse. The collected data were analyzed according to the Kaplan-Meier method. The average follow-up time was 5.6 years. There were 21 patients who suffered a relapse. The probability of successful treatment was 0.77 (range: 0.67-0.88) after 5 years and 0.68 (range: 0.5-0.86) after 10.6 years. We conclude that rubber band ligation represent an efficient long-term treatment for second-degree hemorrhoids. Approximately two thirds of the patients are cured after 5 years and more than a half after 10 years.

T he most common benign tumor of the lung is the hamartoma representing 77%. Hamartomas represent 4% to 8% of all solitary pulmonary nodules, which present themselves as well-circumscribed, asymptomatic coin lesions within the pulmonary parenchyma. Usually they are chondromatous hamartomas consisting of cartilage and are regarded as benign neoplasms derived from the peribronchial mesenchymal tissue. Symptoms such as cough, hemoptysis, or pulmonary infections arise only when the location is endobronchial, which is rare (10%). There is an overall incidental finding in approximately 0.25% of autopsies, and hamartomas are found more frequently in men than in women (2:1). Multiple hamartomas are rare and do not include cartilage but pulmonary muscular or endothelial tissue and are therefore called hemangioleiomyomatous and fibroleiomyomatous hamartomas. In the case of a solitary lesion it is necessary to exclude malignancy. Percutaneous, transthoracic computed tomographyguided needle aspiration biopsy yields diagnosis in 85% of solitary pulmonary coin lesions. The risk of pneumothorax is high, ranging from 20% to 24%. Video-assisted thoracic surgical (VATS) resection offers a safe and 100% sure method to obtain a diagnosis with little discomfort for the patient. Most authors recommend enucleation or tissue-sparing resection of the chondromatous hamartoma. Recurrence after excision is practically unknown.