[Organ Bath Experiments on Human Pulmonary Vessels: Assessment of Drug Efficacy for Treatment of Pulmonary Arterial Hypertension]. / Organbadversuche an humanen Pulmonalgefäßen: Beurteilung der Medikamentenwirkung zur Behandlung der pulmonalarteriellen Hypertonie.

Various vasodilator medications are used in the treatment of pulmonary arterial hypertension (PAH), such as endothelin receptor antagonists (ERA) or phosphodiesterase-5-(PDE-5-)inhibitors. In a human ex vivo model, we investigated whether the combination of two substance classes could achieve a higher effect or - without loss of vasodilatation - a lower dosage of the individual substances might be sufficient. We established an ex vivo organ bath model to evaluate the dose-dependent effects of ERA and PDE-5-inhibitors on pulmonary vessels harvested from patients who underwent surgery (lung resection/transplantation). We compared the combined use of both substance classes with administration of one class of drugs alone. Due to the limitations of the experimental design, it is not possible to extrapolate our results to the conditions in vivo. Nevertheless, organ bath proved to be helpful in evaluating the dose-dependent effects of ERA and PDE-5 inhibitors, which is not practical in everyday clinical practice. In this setting, the effectiveness of the combination therapy and the potential for dose reduction depended on the concentrations used and on the influence of previous illnesses on blood vessel function. This article describes the most important results of our experimental investigations and suggestions for future projects.

Evaluation of the combination of endothelin receptor antagonists (ERA) and phosphodiesterase-5 inhibitors for the treatment of pulmonary arterial hypertension (PAH) in pathologic human pulmonary arteries in an ex-vivo organ bath model.

PURPOSE: Medical combination therapy of pulmonary arterial hypertension (PAH) may alleviate the drawbacks of monotherapy by avoiding drug tolerance and by increasing effectiveness, as shown by the combination of ambrisentan and tadalafil (AMBITION trial). The present ex-vivo study evaluated the combination of the endothelin receptor antagonists (ERA) macitentan and bosentan with the phosphodiesterase-5 (PDE-5) inhibitor vardenafil in pulmonary arteries from patients suffering from terminal lung disease as a model of PAH. METHODS: Segments of the pulmonary vessels were excised from resected lungs of patients requiring lung transplantation (LTX). Contraction of pulmonary arteries (PA) was elicited by consecutive dose-response curves of endothelin-1 (ET-1) followed by norepinephrine (NE) to allow inhibition by different pathways. Forces were measured isometrically in an organ bath in the presence and absence of ERA and PDE-5 inhibitors and their combination. RESULTS: PA of 38 patients were examined between October 2016 and November 2019. Bosentan (1E-7 M) and macitentan (1E-8 M, 3E-8 M, 1E-7 M) inhibited ET-1 induced contractions, whereas vardenafil (1E-6 M, 3E-6 M, 1E-5 M) inhibited only the NE induced part of the contractions. Vardenafil enhanced bosentan-induced inhibition of vasoconstriction in a dose-dependent fashion. Combination effects exceeded single bosentan at 3E-6 M and 1E-5 M vardenafil, and they exceeded single vardenafil at the lower vardenafil concentrations. Macitentan showed a more pronounced inhibition than bosentan regardless of the lower concentrations. Accordingly, combination effects with vardenafil resembled those of macitentan alone. CONCLUSIONS: Macitentan and bosentan were potent antagonists of vasoconstriction in PA of LTX patients. The benefit of drug combinations was demonstrated at selected concentrations only owing to a narrow therapeutic range of vardenafil in this ex-vivo model. These results suggest the utility of drug combinations other than the established pair of ambrisentan and tadalafil in PAH treatment but also make a case for a further assessment of vasodilator properties of drugs complementing ERA.

[Hyperthermic intrathoracic chemotherapy in thoracic surgery]. / Hypertherme intrathorakale Chemotherapie in der Thoraxchirurgie.

In regional chemotherapy of the pleural space a differentiation is made between intrapleural hyperthermic perfusion (IHP) and hyperthermic intrathoracic chemotherapy (HITOC). The HITOC in particular is carried out as an additive procedure after surgical cytoreduction of the pleural tumor manifestation. The main indications are for malignant pleural mesothelioma and thymoma with pleural spread (stage IVa), whereas treatment of secondary pleural carcinomatosis is indicated only in selected patients suitable for resection followed by HITOC. Cisplatin is the standard chemotherapeutic agent and a concentration of 150-175 mg/m2 body surface area is recommended. Postoperative, HITOC-related complications (e.g. renal insufficiency) can be minimized by an adapted perioperative management. Safety measures should be accomplished adhered to for the protection of personnel. The aim of HITOC is to achieve a better local tumor control with a corresponding longer recurrence-free and overall survival.

[Surgical treatment of tracheoarterial fistulas]. / Chirurgische Versorgung tracheoarterieller Fisteln.

BACKGROUND: A tracheoarterial fistula (TAF) is an uncommon but life-threatening complication after tracheostomy. Only an immediate and targeted treatment provides a chance to survive. OBJECTIVE: Surgical treatment of TAF. METHODS: Selective review of the literature and case description. RESULTS: A TAF leads to an acute bleeding complication with displacement of the respiratory tract. The mortality rate is nearly 100% without a surgical intervention. In the literature various interventional and surgical treatment procedures are described. Rapid control of bleeding via manual compression and overinflation of the tracheal cuff are the most important steps of treatment. Subsequent emergency surgery with ligation or resection of the TAF and covering of the tracheal lesion should be performed. Extracorporeal membrane oxygenation (ECMO) and a heart-lung machine can sometimes be necessary. CONCLUSION: Despite all treatment options the mortality rate of TAF remains high. The critical steps are a quick diagnosis of TAF, securing the airway and immediate bleeding control.

[Influence of primary lymph node status of colorectal cancer on the development of pulmonary metastases and thoracic lymph node metastases]. / Einfluss des primären Lymphknotenstatus kolorektaler Karzinome auf die Entwicklung von Lungenmetastasen und thorakalen Lymphknotenmetastasen.

BACKGROUND: The lungs are the second most common organ site for metastases in patients with colorectal cancer (CRC). Lymph node metastasis of CRC represents a prognostic factor for survival. OBJECTIVE: The present study investigated the influence of CRC lymph node metastasis on lung metastasis, in particular thoracic lymph node metastasis. MATERIAL AND METHODS: A retrospective analysis of 88 patients (n = 56 male) with curative resection of lung metastases of CRC was performed. Primary endpoint: influence of lymph node status of CRC on lung metastases. Secondary endpoints: disease-free survival and overall survival. Statistical evaluation was carried out with SPSS. RESULTS: In 48 patients a positive lymph node status of CRC and in 9 patients an N+ status of lung metastases were determined. The lymph node status of the CRC significantly affected the incidence of synchronous metastases (p = 0.03), disease-free interval until formation of metachronous lung metastases (p = 0.012) and the overall survival of patients with CRC (p = 0.048). The 5­year survival rate for CRC patients with lung metastases was 48.7% after pulmonary metastasectomy. Thoracic lymph node involvement also significantly affected survival (p = 0.001). CONCLUSION: Screening for pulmonary metastases should be included in the staging and follow-up of all patients with CRC, especially in patients with a positive lymph node status of the CRC.

[Decortication in Pleural Empyema: Reasonable Effects on Lung Function?]. / Dekortikation bei Pleuraempyem: funktionell sinnvoll?

UNLABELLED: Parapneumonic pleural effusion (PPE) occurring in early-stage (stage I) pleural empyema (PE) can be managed by chest tube drainage, which should be performed as soon as possible, to achieve re-expansion of the pulmonary parenchyma. Chronic disease leads to fibrin deposits on both pleural surfaces (stage II), followed by a thickened pleura peel (stage III). A trapped or compressed lung can only be released by surgical decortication, which may be performed with a minimally-invasive approach (video-assisted thoracoscopy) or an open technique (thoracotomy). This article reviews effects on pulmonary function after decortication in chronic empyema patients. MATERIAL AND METHODS: Selective literature research using Medline (key words: pleural empyema, decortication, lung function). A comparative analysis was performed on functional parameters obtained before and after surgical decortication in patients with chronic pleural empyema. RESULTS: Decortication in chronic PE significantly enhanced spirometric parameters (FEV1, VC/FVC) in all analysed studies. Considerable differences were observed regarding the mean follow-up time (early postoperative to several months after surgery). Computed tomography scans were usually analysed after a minimum of 6 months postoperatively. Measurements of anterior-posterior and transverse diameters as well as volume quantification of the operated and non-operated lung were performed in pre- and postoperative imaging. Statistical comparison revealed a significant decrease in thoracic asymmetry. In addition to static and dynamic pulmonary performance, pulmonary perfusion improved significantly after decortication as demonstrated by lung perfusion scans performed immediately after surgery and during a period of 7 to 10 months thereafter. CONCLUSION: Surgical decortication in chronic pleural empyema improves lung function and increases perfusion. Besides a significant enhancement of spirometric parameters, re-expansion of the diseased lung leads to equalisation of thoracic asymmetry and may even prevent loss of volume in the affected lung.

[Surgical reconstructive procedures of the chest wall after mediastinitis]. / Plastische Rekonstruktionsverfahren der Brustwand nach Mediastinitis.

Sternal osteomyelitis as a direct consequence of advanced mediastinitis or as in most cases after median sternotomy is still associated with a prolonged hospital stay, increased morbidity and postoperative mortality. Early diagnosis and an adequate surgical treatment are decisive for the prognosis. Prerequisites for a secondary stabilization of the chest wall using wires or plates are sterile wound conditions. Diverse reconstructive techniques are available for anterior chest wall reconstruction depending on the defect size and localization. The various reconstructive methods including local and free flap coverage are described in this review article.

[Outcomes of Stage-Adapted Surgical Treatment of Pleural Empyema]. / Ergebnisse der stadienadaptierten chirurgischen Therapie von Pleuraempyemen.

BACKGROUND: The surgical treatment of pleural empyema should be carried out depending on the stage of the disease and the patient's symptoms. The aim of this study was to evaluate the outcomes of surgical pleural empyema treatment. PATIENTS AND METHODS: Retrospective analysis of all patients with pleural empyema treated surgically between January 2008 and December 2013. The primary endpoint of the study was inpatient lethality. Secondary endpoints included duration of inpatient stay, type of treatment (surgical/conservative), proof of pathogen and type, alteration and duration of antibiotic therapy. RESULTS: Of 359 patients, 0.8 % (n = 3) had stage I empyema, 50.4 % (n = 181) had stage II and 48.7 % (n = 175) had stage III. The most frequent causes (32.4 %) included acute pneumonia (parapneumonic pleural empyema), surgery (usually thoracic) in 18.0 % of cases and previous pneumonia (postpneumonic pleural empyema) in 15.4 %. Surgery was performed in 86 % of cases (operative procedures: open thoracotomy 85 %, VATS 15 %). The average duration of inpatient stay was 20 days for stages II and III. Recovery following VATS was significantly shorter in stage II compared to thoracotomy (p = 0.022). Hospital lethality amounted to 7.0 % (25 patients). The lethality rate was 5.5 % (10/185) in stage II and 8.6 % (15/175) in stage III. Patients with confirmed pathogens had a significantly worse mortality rate across all stages (9.8 %) than patients with no confirmed pathogens (4.0 %, p = 0.034). Age, malignant underlying disease, multiple comorbidities, immunosuppression, a change in antibiotic regimens and sepsis were significant risk factors. CONCLUSION: The inpatient lethality of patients with pleural empyema correlates with the stage of the condition. Positive confirmation of pathogens, sepsis, a higher age, multiple comorbidities, malignant tumour disease, immunosuppression and a change of antibiotics are negative prognostic factors.

[Para- and Postpneumonic Pleural Empyema: Current Treatment Strategies in Children and Adults]. / Para- und postpneumonisches Pleuraempyem: aktuelle Behandlungsstrategien bei Kindern und Erwachsenen.

INTRODUCTION: Parapneumonic pleural effusions arise from pneumonia and may develop into pleural empyema (PE). PE is defined as collection of pus in the pleural space with secondary inflammation of the visceral and parietal pleura. This review article describes the current treatment strategies for para- and postpneumonic PE both in children and adults. MATERIAL AND METHODS: Selective literature research via Medline (key words: pleural empyema, pleural empyema in children, thoracic empyema) and presentation of our own clinical experience with therapy recommendations. RESULTS: The incidence of postpneumonic PE is increasing in both children and adults. PE is associated with a high morbidity and mortality if it is not treated early and adequate. Progression of PE follows a characteristic morphological course, which is classified in three stages: the exsudative, fibrinopurulent, and organizing phase. Treatment should be adapted to these three phases including systemic antibiotic therapy and drainage of the pleural space. Intrapleural fibrinolysis can be performed with good success independent of age in the transition of stage 1 and 2. In persistent PE (stage 2), thoracoscopic decortication is recommended to avoid progression into the organizing phase (stage 3) with the need of an open decortication. In debilitated elderly patients the increasing use of intrathoracic vacuum therapy (Mini-VAC/Mini-VAC-instill) offers an effective and less invasive therapy option. CONCLUSION: Para- and postpneumonic PE requires an individualized and stage adapted therapy using a combination of medical and surgical treatment strategies with the aims of removing the source of infection and ensuring re-establishment of lung expansion.

[Intrathoracic Vacuum-Assisted Closure in the Treatment of Pleural Empyema and Lung Abscess]. / Intrathorakale Vakuumtherapie beim Pleuraempyem und Lungenabszess.

BACKGROUND: Complex pleural empyema or lung abscesses are either characterised by long-standing treatment (including treatment failure) or by a bad general condition of the patient (multiple morbidity, sepsis). The operative rectification is often associated with increased morbidity and mortality rates in these cases. Traditionally, the therapeutic tendency for such patients was towards primary creation of a thoracic window including open wound treatment, but this was always also associated with a long sickness and restrictions in the quality of life. The intrathoracic vacuum treatment (VAC) offers here entirely new options in the treatment of complicated pleural empyema and lung abscesses. METHOD: We present an illustration of our own clinical experience associated with a selective literature research via Medline (keywords: VAC, vacuum-assisted closure, thoracic empyema). RESULTS: After the initial successes of the extrathoracic application of the VAC treatment, the procedure was also analysed for its intrathoracic/pleural use to treat pleural empyema and lung abscesses with and without bronchus stump insufficiency. Initially, the use of the intrathoracic VAC treatment was carried out via a thoracic window (with rib resection), later we developed a minimally invasive procedure (Mini-VAC) while relieving the osseous thorax. An additional intrapleural rinsing with antiseptics (Mini-VAC-Instill) is very practical in cases of proven germ populations. The benefits of the Mini-Vac/Mini-VAC-Instill are: immediate secretion suction with quick local cleaning, rapid germ eradication with a small risk of a fresh population, improvement of the expansion behaviour of the lung as well as short treatment times with quick reclosure of the thorax. In addition to many retrospective examinations, there has so far only been one cohort study in which the classic thoracic window was compared with the VAC treatment. The duration of the stomatic situation as well as the long-term survival in the VAC group were better here than those in the non-VAC group. CONCLUSION: The intrathoracic VAC treatment (Mini-Vac/Mini-VAC-Instill) is an innovative procedure that promotes wound cleaning and wound healing in complicated pleural empyema and lung abscesses. Due to the benefits of this procedure, including the improvement of the patient's comfort and the quality of life, the procedure has seen a rapid and broad clinical acceptance.

[Persistent pleural effusion following thoracic surgery]. / Persistierender Erguss nach thoraxchirurgischen Eingriffen.

BACKGROUND: Persistent postoperative pleural effusion can occur after thoracic surgery and might lead to progressive dyspnea with a subsequent complicated and prolonged hospital stay. OBJECTIVES: The etiology, prevention and therapy of persistent pleural effusion after thoracic surgical interventions are presented. MATERIAL AND METHODS: A selective literature search was carried out in Medline (pleural effusion, pleural empyema and chylothorax). RESULTS: Persistent pleural effusions were observed especially after lung resection due to disorders in the pleural fluid balance and reduced postoperative lung expansion. An adequate chest tube management and postoperative physical therapy can reduce the incidence of postoperative pleural effusion. Relevant postoperative bleeding causes a hemothorax. An infection of the pleural effusion is defined as pleural empyema. These patients suffer from a significantly higher postoperative morbidity and require an adjusted multimodal treatment. Intraoperative injury of the thoracic duct can result in a postoperative chylothorax, which should be diagnosed early with specific laboratory investigations of the milky fluid. Interventional radiological procedures have now taken their place alongside conservative measures and surgical procedures in the therapy of chylothorax. CONCLUSION: Persistent postoperative pleural effusion after thoracic surgical interventions warrant early diagnosis and an adjusted treatment in order to avoid further complications and to shorten the postoperative hospital stay.

[Perioperative antibiotic therapy in thoracic surgery]. / Perioperative Antibiotikatherapie in der Thoraxchirurgie.

INTRODUCTION: In Germany no official guidelines exist for a specific perioperative antibiotic prophylaxis (PAP) in thoracic surgery. In this review, data regarding the PAP as well as antibiotic therapy of the postoperative pneumonia (POP) in thoracic surgery are described. METHODS: Selective literature researches were carried out in Medline with consideration of the official recommendations of the Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF) as well as Paul-Ehrlich-Gesellschaft für Chemotherapie e. V. (PEG). RESULTS: The PAP is defined as a short and single application of an antibiotic agent preoperatively or during a surgical intervention. A PAP with first-generation or second-generation cephalosporins could significantly reduce the rate of surgical site infections after thoracic surgery. However, these few randomised trials could not demonstrate a distinct effect on the rate of POP and postoperative empyema. The incidence of POP is approximately 20-25 % after major thoracic surgery. Antibiotic therapy of POP should be performed early and be based on antibiotic sensitivity. CONCLUSION: Based on the few prospective, randomised studies a single dose of intravenous PAP with a cephalosporin is recommended in thoracic surgery. Therapy of the POP should include general procedures combined with a specific antibiotic therapy according to antibiotic sensitivity.

[Radical pleurectomy and hyperthermic intrathoracic chemotherapy for treatment of thymoma with pleural spread]. / Radikale Pleurektomie und hypertherme intrathorakale Chemotherapie zur Behandlung pleural metastasierter Thymome.

INTRODUCTION: Patients with pleural thymoma spread (Masaoka stage IV a) should be treated within a multimodal treatment regime. However, the extent of local surgical resection to achieve optimal tumour control remains controversial. PATIENTS AND METHODS: Prospective analysis between September 2008 and April 2013 of all patients with a Masaoka stage IV a thymoma, who underwent radical pleurectomy/decortication (P/D) followed by hyperthermic intrathoracic chemotherapy (HITHOC). RESULTS: A total of 11 patients (male n = 7; mean age 46.5 ± 11.4 years) with a primary stage IV a thymoma (n = 3) or thymoma with pleural relapse (n = 8) were included after successful transsternal thymoma resection. WHO histological classification was: B1 n = 1, B2 n = 6, B3 n = 3 and C n = 1. A radical P/D (5/11; 45 %) was extended with resection of the pericardium and diaphragm in 6/11 (55 %) patients. After surgical resection (91 % complete macroscopic R0/R1-resection) the HITHOC with cisplatin (100 mg/m2 body surface area (BSA) n = 7; 150 mg/m2 BSA n = 4) was performed for one hour at 42 °C. Operative revision was necessary in two patients (chylo- and hematothorax) with one patient also requiring temporary renal replacement therapy due acute renal failure (cisplatin 150 mg/m2 BSA). 30-day mortality was 0 %. Local recurrence (pulmonary n = 1, paravertebral n = 2) was documented in 3/10 (30 %) patients after R0/R1 resection. After a mean follow-up of 23 months the overall median survival was 27 months and 82 % (9/11) patients are still alive at the end of the study period. CONCLUSIONS: Masaoka stage IV a thymoma could be safely treated with lung-sparing radical P/D and HITHOC with cisplatin in a multimodality treatment regime. Early results with respect to recurrence and survival are encouraging, but further studies are warranted and we have to await long-term results.

[Regional treatment of malignant pleural mesothelioma: results from the tumor centre Regensburg]. / Regionale Versorgung des malignen Pleuramesothelioms : Ergebnisse aus dem Tumorzentrum Regensburg.

INTRODUCTION: Malignant pleural mesothelioma (MPM) is an aggressive, malignant tumor of the pleural surface and is strongly associated with asbestos exposure. Incidence of MPM will reach its peak over the coming years. Most patients present with advanced tumor stages and therefore surgical options are limited. PATIENTS AND METHODS: Retrospective analysis of all patients with MPM reported to the tumor centre Regensburg between January 1998 and August 2011. RESULTS: A total of 118 patients (85 % male) with cytologically or histologically confirmed MPM were reported. The mean age at diagnosis was 67 years (range 45-84 years) and 65 % of patients had a history of asbestos exposure. The incidence of MPM at the tumor centre Regensburg was 0.8/100,000 inhabitants with obvious regional differences depending on asbestos exposure. Staging was completed in 81 patients (67 %): stage I 9 %, stage II 22 %, stage III 23 % and stage IV 46 %. Of the patients 87 (74 %) underwent at least one surgical procedure: diagnostic thoracoscopy with biopsy (n = 37, 43 %), debulking surgery or talcum pleurodesis (n = 33, 38 %) and potentially curative resection (n = 17, 19 %). After a mean follow-up of 20 months the overall median survival was 14 months (1 year survival rate 62 %, 3 year survival rate 15 %). Patients had a significantly better median survival of 18 months after curative resection. CONCLUSIONS: The distribution of MPM varies according to regional and industrial asbestos exposure. Screening and diagnostics should concentrate on locations with higher incidence of MPM to facilitate surgical therapy in a multimodal treatment regime.

[Intraoperative chemotherapy after radical pleurectomy or extrapleural pneumonectomy]. / Intraoperative Chemotherapie nach radikaler Pleurektomie oder extrapleuraler Pneumonektomie.

Trimodality treatment including induction and/or adjuvant chemotherapy, surgical resection and in some cases radiotherapy offers a curative intention in selected patients with pleural malignancies (malignant pleural mesothelioma, thymoma with pleural spread). Nevertheless, locoregional tumor recurrence mainly limits the outcome and the quality of life. A few years ago an additional intraoperative chemotherapy perfusion was developed in order to improve local tumor control and prognosis after surgical resection in a multimodality treatment setting. Cytoreductive surgery with the purpose of a macroscopic complete resection could be achieved by radical pleurectomy or extrapleural pneumonectomy. The concept, techniques and perioperative management of this additional treatment option are presented along with a detailed review of the recent literature.

Local and systemic exposure of cisplatin during hyperthermic intrathoracic chemotherapy perfusion after pleurectomy and decortication for treatment of pleural malignancies.

BACKGROUND: Assessing the pharmacokinetics of intrapleurally administered cisplatin during hyperthermic intrathoracic chemotherapy perfusion (HITHOC) following pleurectomy/decortication in patients with malignant pleural mesothelioma or advanced thymoma with pleural spread. METHODS: Pharmacokinetic analysis (ICP-MS) of intrapleural cisplatin with a dosage of 100 mg/m(2) (n = 5) or 150 mg/m(2) (n = 5) at 42°C perfusate temperature. Simultaneous pleural perfusion fluid and serum samples were collected at the beginning and every 15 min. Serum samples were collected at the end of the operation, 6, 12, and 24 hr postoperative. RESULTS: Mean cisplatin levels in the perfusate slightly decreased during the HITHOC. The mean area under the curve ratios (AUC perfusate :AUC serum ) of cisplatin were nearly similar. The mean AUCs of cisplatin in the perfusate were approximately 58 and 55 times greater than detected in the serum. The mean peak of cisplatin in the serum was reached after 1 hr of HITHOC. The AUC of cisplatin in the serum did not significantly differ (P = 0.18) between both groups up to 24 hr after perfusion. CONCLUSIONS: HITHOC with cisplatin provides a pharmacological advantage of high local intrapleural cisplatin concentrations. Elevation of the cisplatin dosage to 150 mg/m(2) did not lead to a significant increase of the systemic cisplatin concentration.

Surgical resection of thymoma still represents the first choice of treatment.

OBJECTIVE: The aim of this study was to analyze the clinicopathological factors, treatment strategies and survival rates after surgical resection of thymoma. METHODS: Between 12/1997 and 5/2010, 42 patients underwent surgical resection of the thymus. The presence of a thymoma was determined by histological examination in 23 patients, while patients with hyperplasia of the thymus (n = 19) were excluded from further analysis. RESULTS: Myasthenia gravis coexisted in 9/23 (39.1%) patients. Thymomas were classified according to the Masaoka staging system (I: n = 6 [26.1%], IIa: n = 7 [30.4%], IIb: n = 2 [8.7%], III: n = 1 [4.4%], IVa: n = 7 [30.4%]) and the WHO histological classification (A: n = 4 [17.4%], AB: n = 5 [21.7%], B1: n = 1 [4.4%], B2: n = 8 [34.8%], B3: n = 3 [13%], C: n = 2 [8.7%]). Recurrence of thymoma was documented in three (13%) patients. After a mean follow-up of 58.4 months, 21 (91.3%) patients are alive. The overall survival rate was 95% and 87.8%, at 2 and 5 years, respectively. The disease-free interval at 5 years was 85% for the 17 (73.9%) patients with complete resection. CONCLUSIONS: Surgical resection of thymoma is the preferred treatment, because it is safe and effective with a low rate of recurrence and a good long-term survival. Advanced and invasive thymomas require a multimodal approach for better local tumor control and further improvement of prognosis.

Mild-to-moderate COPD as a risk factor for increased 30-day mortality in cardiac surgery.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is still a serious comorbidity in surgical procedures. We assessed the impact of mild to moderate COPD in a modern cardiac surgery unit. METHODS: An age-, gender- and operation-matched cohort analysis of 242 patients treated between 01/2006 and 12/2008 was performed. COPD was defined as a FEV1 < 80 % and a FEV1/FVC ratio < 0.7 in preoperative spirometry. Primary end point was 30-day mortality. RESULTS: Preoperative beta-agonist treatment of COPD patients was noted for 43 % of patients and not in the control group. After comparable surgery, postoperative respiratory failure was more frequent in COPD patients (10.4 % vs. 2.5 %, P = 0.02), whereas median ventilation time (12 h) and rate of reintubation (2.5 % vs. 3.5 %) did not significantly differ between both groups. Intensive care and hospital stay were significantly longer in the COPD group ( P = 0.02 and P = 0.04), and 30-day mortality was significantly higher in COPD patients (0.8 % vs. 6.1 %, P = 0.03). CONCLUSIONS: COPD increases 30-day mortality, postoperative pulmonary complications, ICU stay and hospital stay. Proper identification and therapy may help to improve outcome in this high-risk population.

Receptor targeting of adeno-associated virus vectors.

Adeno-associated virus (AAV) is a promising vector for human somatic gene therapy. However, its broad host range is a disadvantage for in vivo gene therapy, because it does not allow the selective tissue- or organ-restricted transduction required to enhance the safety and efficiency of the gene transfer. Therefore, increasing efforts are being made to target AAV-2-based vectors to specific receptors. The studies summarized in this review show that it is possible to target AAV-2 to a specific cell. So far, the most promising approach is the genetic modification of the viral capsid. However, the currently available AAV-2 targeting vectors need to be improved with regard to the elimination of the wild-type AAV-2 tropism and the improvement of infectious titers. The creation of highly efficient AAV-2 targeting vectors will also require a better understanding of the transmembrane and intracellular processing of this virus.

Real-time single-molecule imaging of the infection pathway of an adeno-associated virus.

We describe a method, based on single-molecule imaging, that allows the real-time visualization of the infection pathway of single viruses in living cells, each labeled with only one fluorescent dye molecule. The tracking of single viruses removes ensemble averaging. Diffusion trajectories with high spatial and time resolution show various modes of motion of adeno-associated viruses (AAV) during their infection pathway into living HeLa cells: (i) consecutive virus touching at the cell surface and fast endocytosis; (ii) free and anomalous diffusion of the endosome and the virus in the cytoplasm and the nucleus; and (iii) directed motion by motor proteins in the cytoplasm and in nuclear tubular structures. The real-time visualization of the infection pathway of single AAVs shows a much faster infection than was generally observed so far.