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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.

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/m 2 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.

Purpose: Treatment of pulmonary arterial hypertension (PAH) by vasodilator drug monotherapy is often limited in its effectiveness. Combination therapy may help to improve treatment and to reduce drug toxicity. This study assessed the combination of the endothelin receptor antagonist macitentan and the phosphodiesterase-5 inhibitor vardenafil in a human ex vivo model., Methods: Study patients did not suffer from PAH. Human pulmonary arteries (PA) and veins (PV) were harvested from resected pulmonary lobes. Contractile forces of blood vessel segments in the presence and absence of the vasodilator drugs macitentan, its main metabolite ACT-132577, and vardenafil were determined isometrically in an organ bath., Results: Macitentan 1E-7 M was sufficient to significantly abate endothelin-1-induced vasoconstriction in PA. A concentration of 1E-6 M was required for significant effects of macitentan on PV and of ACT-132577 on both vessel types. Combination of 1E-7 M macitentan and 1E-6 M vardenafil inhibited sequential constriction with endothelin-1 and norepinephrine of PA significantly more than either compound alone. Effects of 3E-7 M and 1E-6 M macitentan and effects of all doses of ACT-132577 were not further enhanced by 1E-6 M vardenafil., Conclusions: These data suggest that vasodilator effects of macitentan and vardenafil combined may surpass monotherapy in vivo if drug doses are adjusted properly. Vasodilation by the longer-acting metabolite ACT-132577 was not further enhanced by vardenafil.

The multimodal treatment of limited peritoneal metastases may improve prognosis in selected patients (pseudomyxoma peritonei, malignant peritoneal mesothelioma, colorectal, gastric and ovarian cancer) provided complete cytoreduction can be performed. Additive intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) is often performed. If the treatment is undertaken in experienced (and certified) centres, associated mortality is low. Intrapleural hyperthermic chemoperfusion (HITOC) can be performed in patients with pleural malignancies, mainly for malignant pleural mesothelioma or metastases from a thymoma. In single patients, pleural metastases from gastrointestinal malignancies might be an indication. Both therapies (HIPEC and HITOC) are complex and their exact role has to be defined within further prospective randomised trials., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (Georg Thieme Verlag KG Stuttgart · New York.)

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 5‑year 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.

Background and Objectives: The prevalence of chronic obstructive pulmonary disease (COPD) and lung emphysema increases with age and both lung diseases are again risk factors for lung cancer. Since a reduced capacity of fibroblasts for proliferation is a good indicator of tissue aging, we studied the cell proliferation of lung fibroblasts from normal and tumor tissue of lung cancer patients depending on lung comorbidities., Material and Methods: Fibroblasts were isolated from tumor and normal lung tissue of 40 lung cancer patients. Cumulative population doubling (CPD) was determined to assess the proliferation capacity, and the PCR technique was used to measure telomere lengths. Since many patients had previously been exposed to severe air pollution, we also studied the effect of air pollution particles on the fibroblast CPD in vitro., Results: Fibroblasts from tumor and normal lung tissue had comparable CPDs; however, the CPD of fibroblasts from both tumor and normal lung tissue was significantly reduced in patients also suffering from COPD. This CPD reduction was highest in COPD patients who had already developed emphysema or were smokers. A significant correlation between CPD and telomere length was identified only for fibroblasts of non-COPD patients. Further studies also showed an adverse effect of air pollution particles on the CPD of lung fibroblasts., Conclusion: Lung cells of COPD patients are characterized by accelerated senescence which must have been initiated prior to lung tumorigenesis and cannot depend on telomere shortening only. In addition to smoking as a known risk factor for COPD and lung cancer, air pollution particles could be another reason for the accelerated senescence of lung cells.

Objectives: Preoperative computed tomography (CT) scans for transcatheter aortic valve implantation (TAVI) are used routinely. In elderly high-risk patients, incidental radiographic findings are frequently reported. The aim of this study was to investigate the impact of auxiliary findings on the patients' mid-term survival, which might affect the treatment strategy., Methods: Between March 2011 and April 2016, all radiological reports of contrast-enhanced CT scans of 976 patients scheduled for TAVI were analysed retrospectively for incidental thoracic findings including solitary pulmonary nodules (SPN) and thoracic lymphadenopathy (LAP). The minimum follow-up period was 1 year after TAVI., Results: The median age of all patients was 79 years; 51.9% (n = 507) were women. Approximately 37% (n = 361) of patients showed 1 of the determined findings. An SPN ≥5 mm was diagnosed in 16.4% (n = 160) of patients. Four of them developed lung cancer and 2 nodules were identified as metastases during follow-up. In addition, 12% (n = 117) of the patients had thoracic LAP. Whereas SPN had no significant effect on the overall survival rate, evidence of LAP turned out to be a statistically significant factor regarding 4-year survival (P = 0.001; hazard ratio 1.66; 95% confidence internal 1.19-2.31)., Conclusions: SPN ≥5 mm were detected in 16.4% of patients scheduled for TAVI. Nevertheless, the incidence of lung cancer was low and the effect on survival in this high-risk group of patients was statistically not significant. In contrast, thoracic LAP had a significant negative effect on survival. It needs to be proven if the outcome of this cohort can be enhanced by further diagnostics and therapy., (© The Author(s) 2018. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Introduction: Patients with severe respiratory failure and veno-venous extracorporeal membrane oxygenation (vv-ECMO) often require diagnostic or therapeutic thoracic surgery., Methods: Retrospective analysis of prospectively collected data (Regensburg ECMO Registry) on all patients requiring vv-ECMO between December 2010 and December 2016 due to acute lung failure (ALF) with diagnostic or therapeutic thoracic surgery. Endpoints were the indications for thoracic surgery as well as postoperative morbidity and in-hospital mortality., Results: A total of 418 patients (male n = 285, 68%, mean age 50.0 ± 16.5 years) with severe respiratory insufficiency refractory to conventional therapy required vv-ECMO. Indications for vv-ECMO were ALF due to pneumonia (59.8%), postoperative (18.7%), posttraumatic (9.8%), after chemotherapy (2.8%) and others (8.9%). Overall, in 24.4% (n = 102) of patients with vv-ECMO surgery was performed. Of these, 28.4% (n = 29) of patients required thoracic surgery. Primary indications for thoracic surgery were most frequently therapeutic due to hemothorax (n = 13; 44.8%), followed by carnifying pneumonia/pulmonary abscess (n = 5; 17.2%), pleural empyema (n = 3; 10.3%) and others (n = 3; 10.3%). In patients with interstitial lung disease of unknown origin (n = 5; 17.2%), diagnostic pulmonary biopsy was performed. For initial thoracic intervention thoracotomy was carried out in 93.1% (n = 27) of patients, whereas only two patients (6.9%) received thoracoscopy. At least one repeated thoracotomy was performed in 15 patients (51.7%) and nine patients (31.0%) underwent more than two surgeries. In-hospital mortality of patients with thoracic surgery (44.8%) was higher than in patients without thoracic surgery (35.7%; p = 0.326)., Conclusion: Thoracic surgery in patients with vv-ECMO warrants strict indications, because postoperative complications are common and surgical revision (58,6%) is often required. Therefore, ECMO therapy should only be carried out in specialised centers with thoracic surgery., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: Patients with respiratory failure are treated more frequently with venovenous extracorporeal membrane oxygenation (vv-ECMO). These patients are at risk for bleeding due to complex multifactorial coagulation disorders resulting from the extracorporeal circulation., Methods: A retrospective analysis was conducted of prospectively collected data on all patients requiring vv-ECMO between December 2010 and December 2016. End points were the incidence, consequence, and in-hospital mortality of patients with thoracic bleeding complications., Results: The study included 418 patients (aged 50 ± 16.5 years) requiring vv-ECMO. In 23.2% (n = 97) of patients, relevant hemorrhage was documented. Thoracic bleeding developed in 40 patients (41.2%), followed by diffuse (21.6%), cerebral (14.4%), gastrointestinal (6.2%), cannulation site (6.2%), and other bleeding locations. Thoracic bleeding complications occurred spontaneously (40%), postoperatively (37.5%), after interventions (20%), and after trauma (2.5%). A thoracic operation was performed in 60% (n = 24) of these patients, and a repeated operation due to bleeding was necessary in 45.8%. Mean ECMO duration (18.6 ± 16.8 days; p = 0.035) and hospital length of stay (58 ± 50 days; p = 0.002) were significantly longer than that in patients without bleeding. In-hospital mortality was significantly higher in patients with thoracic bleeding complications (52.5%) than in patients without bleeding complications (32.7%; p = 0.013)., Conclusions: Thoracic bleeding complications were observed in 9.6% of patients and represented the most frequent bleeding complication during vv-ECMO treatment. Almost 60% of patients required surgical revision, and nearly half of these patients underwent a repeated operation. Because mortality is high in these patients, vv-ECMO should be performed in only centers experienced with thoracic surgery., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The optimal treatment of primary spontaneous pneumothorax (PSP) is still controversial. The purpose of this study was to analyze the incidence of recurrence, the recurrence-free time, and to identify risk factors for recurrence after PSP., Methods: We performed a retrospective analysis of 135 patients with PSP who were treated either conservatively with a chest tube ( n  = 87) or surgically with video-assisted thoracoscopic surgery (VATS; n  = 48) from January 2008 through December 2012., Results: In this study, 101 (74.8%) male and 34 (25.2%) female patients were included with a mean age of 35.7 years. The indications for surgery included blebs/bullae in the radiological images ( n  = 20), persistent air leaks ( n  = 15), or the occupations/wishes of the patients ( n  = 13). A first ipsilateral recurrent pneumothorax (true recurrence) was observed in 31.1% of all patients (VATS: 6.25%, conservative: 44.8%). Including contralateral recurrence, the overall first recurrence rate was 41.3% (VATS: 14.6%, conservative: 57.5%). The recurrence-free time did not differ significantly between the treatment groups ( p  = 0.51), and most recurrences were observed within the first 6 months after PSP. Independent risk factors identified for the first recurrence were conservative therapy ( p  = 0.0001), the size of the PSP (conservative; p  = 0.016), and a body mass index <17 (VATS; 0.022). The risk for second and third recurrences of PSP was 17.5 and 70%, respectively, for both treatment groups, but it was 100% after conservative therapy., Conclusion: Surgery for PSP should be selected based on the risk factors and the patient's wishes to prevent first recurrences but also to avoid overtreatment. The treatment of first and subsequent PSP recurrences should be with surgery since conservative treatment is associated with a 100% recurrence rate., Competing Interests: There is no conflict of interest and nothing to disclose., (Georg Thieme Verlag KG Stuttgart · New York.)

In Germany, 10,000 cases of spontaneous pneumothorax are treated inpatient every year. The German Society for Thoracic Surgery (DGT), in co-operation with the German Society for Pulmonology (DGP), the German Radiological Society (DRG) and the German Society of Internal Medicine (DGIM) has developed an S3 guideline on spontaneous pneumothorax and postinterventional pneumothorax moderated by the German Association of Scientific Medical Societies (AWMF)., Method: Based on the source guideline of the British Thoracic Society (BTS2010) for spontaneous pneumothorax, a literature search on spontaneous pneumothorax was carried out from 2008 onwards, for post-interventional pneumothorax from 1960 onwards. Evidence levels according to the Oxford Center for Evidence-Based Medicine (2011) were assigned to the relevant studies found. Recommendations according to GRADE (A: "we recommend"/"we do not recommend", B: "we suggest"/"we do not suggest") were determined in three consensus conferences by the nominal group process., Results: The algorithms for primary and secondary pneumothorax differ in the indication for CT scan as well as in the indication for chest drainage application and video-assisted thoracic surgery (VATS). Indication for surgery is recommended individually taking into account the risk of recurrence, life circumstances, patient preferences and procedure risks. For some forms of secondary pneumothorax, a reserved indication for surgery is recommended. Therapy of postinterventional spontaneous pneumothorax is similar to that of primary spontaneous pneumothorax., Discussion: The recommendations of the S3 Guideline provide assistance in managing spontaneous pneumothorax and post-interventional pneumothorax. Whether this will affect existing deviant diagnostic and therapeutic measures will be demonstrated by future epidemiological studies., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: The Masaoka-Koga classification describes the extent and spread of thymic epithelial malignancies. The objective of this study was to evaluate the Masaoka-Koga and the new TNM-staging system regarding differences in stage distributions, clinical implementation and therapeutic consequences., Methods: Retrospective analysis of all patients who underwent surgery between January 2005 and December 2015 for thymoma/thymic carcinoma in two centres for thoracic surgery. The final tumour stages were determined on the basis of preoperative imaging, surgical reports and histological findings., Results: A total of 118 patients (male 51%) with a mean age of 56 ± 14.8 years were included. Indications for surgery were primary mediastinal tumour (n = 97), pleura dissemination (n = 15) or mediastinal recurrence (n = 7). Radical tumour resection was performed in 92% of patients (n = 109) within one operation, whereas 8% of patients (n = 9) underwent two operations. Surgical revision was necessary in 12 patients (10.1%) and in-hospital mortality was 1.7% (n = 2). Early Masaoka-Koga stages I (n = 34) and II (n = 16) shifted to the new UICC stage I (T1: n = 58). Locally advanced stages (Masaoka-Koga stage III n = 22 vs. UICC stage IIIA + IIIB n = 20) and metastasised stages (Masaoka-Koga stage IV n = 36 vs. UICC stage IV n = 39) remained very similar., Conclusions: The new TNM staging system gave rise to changes, especially in early stages (downstaging), but these had no therapeutic implications. Although advanced stages were very similar, the new TNM staging provides more clinically relevant differentiation., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (Georg Thieme Verlag KG Stuttgart · New York.)

Introduction: For several years, hyperthermic intrathoracic chemotherapy (HITHOC) has been performed in a few departments for thoracic surgery in a multimodality treatment regime in addition to surgical cytoreduction. Specific data about HITHOC in Germany are still lacking., Methods: Survey in written form to all departments of thoracic surgery in Germany. The objective is the evaluation of HITHOC with respect to number, indications, technique, perioperative protection measure and complications., Results: A total of 116 departments of thoracic surgery were contacted, with a return rate of 43% (n = 50). HITHOC was not performed in 33 departments, due to lack of resources or experience (n = 17), missing efficacy of the procedure (n = 8) and fear of excessive complication rates (n = 3). Since 2008, a total of 343 HITHOC procedures have been performed in 17 departments. Eight departments have their own perfusion machine, whereas the remaining departments borrow the perfusion machine. Indications were malignant pleural mesothelioma in all departments (n = 17), thymoma with pleural spread (n = 11) and secondary pleural carcinosis (n = 7). The HITHOC was performed in nearly all departments after closing the chest (n = 16), with a temperature of 42 °C (n = 12) and for 60 minutes (n = 15). Cisplatin was always used, either alone (n = 9) or in combination (n = 8). In all the participating departments, the aims of the HITHOC were improvement in local tumor control and prolonged recurrence-free and overall survival. Relevant HITHOC-associated complications were low., Conclusions: HITHOC is performed in at least 17 departments of thoracic surgery in Germany, and is widely standardised with protective measures and a low rate of complications. The aims of the HITHOC are improvement in local tumor control in pleural malignancies combined with prolonged overall survival and better quality of life., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: Non-small cell lung cancer (NSCLC) with mediastinal lymph node involvement (N2) is a heterogeneous entity. The objective of this analysis is to investigate the results of treatment strategies for N2-positive patients., Methods: Retrospective study (2009-2014) of 104 consecutive patients with stage IIIA-N2 NSCLC classified according to the Robinson classification (IIIA1-IIIA4) and treated within a multimodality treatment regime., Results: The Robinson subgroups were: IIIA1 (n=27), IIIA3 (n=60) and IIIA4 (n=17). We had no stage IIIA2 samples because we did not perform an intraoperative frozen section of lymph nodes. Surgical resection with systematic lymph node dissection was performed in all patients with stage IIIA1 (n=27). After chemotherapy or chemo-/radiotherapy, 53.3% of patients in stage IIIA3 (n=32) and 11.7% of patients in stage IIIA4 (n=2) underwent surgery with curative intention. R0 was achieved in 92.6% in stage IIIA1, 93.8% in stage IIIA3 and 100% in stage IIIA4. The 30-day mortality was 3.2%. The overall median survival was 31.7 months (5-year survival was 30.5%). There were no significant differences (P=0.583) in survival regarding the Robinson subgroups. Patients who underwent tumour resection had significantly better median survival (39.8 vs. 19.6 months; P=0.014) compared to patients treated conservatively. Deviation from the interdisciplinary recommended therapy (12%) led to a reduced median survival (11.4 vs. 31.8 months; P=0.137)., Conclusions: N2-patients should be subclassified according to the Robinson classification and discussed in the tumour board. Surgical resection should be recommended in specific cases of N2-disease (non-bulky, sensitivity to systemic treatment)., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Introduction: Pseudotumour of the lung is a collective term for various subentities. Some subgroups are considered to be intermediary malignant tumours. A pseudotumour is a rare condition, which makes it difficult to estimate its incidence and prevalence., Methods: Retrospective analysis of all surgically treated patients between 2008 and 2015 diagnosed with a pseudotumour of the lung. The primary endpoint of this study was to estimate the rates of local recurrence and metastasis. Secondary endpoints were to determine the nomenclature, medical history, treatment, and the perioperative course., Results: Out of 27 patients (10 females and 17 males) with a median age of 58 years, 19 patients (70%) had an inflammatory pseudotumour (IPT), and four patients (15%) had an inflammatory myofibroblastoma (IMT). Two patients had a pneumocytoma/histiocytoma. A preoperative pulmonary infection was present in 12 (44%) patients. The average tumour size was 2.1 cm (0.8 - 5.3 cm), with the lower pulmonary lobes being mostly affected (52%). One enucleation, 20 atypical wedge resections and six anatomical resections were performed. This was done in a minimally invasive procedure (VATS) in 48% of cases (13/27). R0 resection was achieved in 93% of cases (25/27). Complications occurred in seven (26%) patients. The difference between the duration of hospital stay (mean duration 8 days) after open resection and VATS was minimal (8.8 vs. 7.2 days). Patients were followed up over a period of 4 years, during which time only one patient developed a tumour recurrence, which led to the patient's death, although she had had a R0 resection of an IMT., Conclusions: The treatment of choice for pseudotumours of the lung is R0 resection, preferably with VATS. Most patients have a benign course of disease, although relapses are possible in some cases, especially in IMT. Follow-up monitoring is necessary for IMT. The application of a uniform nomenclature and classification would be a sensible approach., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (Georg Thieme Verlag KG Stuttgart · New York.)

Objectives: A tracheoarterial fistula (TAF) is an uncommon but a critical complication of tracheostomy and represents a surgical emergency. Surgical therapy with ligation of the brachiocephalic trunk can be considered as the first choice of treatment to control massive and life-threatening haemorrhage., Methods: We describe 3 cases of TAF in patients who had long-term placement of a tracheostomy tube and the occurrence of a severe massive haemorrhage caused by an injured brachiocephalic trunk. All cases required emergent surgical revision. Different surgical techniques were used. In addition to the 3 case reports, we present a review of the literature of published TAF cases, summarize the different measures to control bleeding and compare the operative procedures used in the treatment of TAF., Results: The occurrence of TAF is rare and constitutes a surgical emergency. The mortality rate of tracheoarterial erosion is 100% without surgical intervention for active bleeding into the airway. Therefore, rapid control of bleeding (via digital compression and an overinflated cuff) is the most important and first step of therapy. Subsequent emergency surgery with ligation and resection of the TAF and covering of the trachea should be considered to finally control the massive haemorrhage. In addition, cardiopulmonary bypass and circulatory arrest can be useful for surgical treatment of cases with uncontrollable bleeding., Conclusions: The mortality rate after resection of the fistula remains high. Finally, the most important factors for patient survival and outcomes are quick diagnosis of the TAF and immediate surgical control of bleeding., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: The objective of this study is the evaluation of the Masaoka-Koga and the International Association for the Study of Lung Cancer (IASLC)/International Thymic Malignancy Interest Group (ITMIG) proposal for the new TNM-staging system on clinical implementation and prognosis of thymic malignancies., Methods: A retrospective study of 76 patients who underwent surgery between January 2005 and December 2015 for thymoma. Kaplan-Meier survival analysis was used to determine overall and recurrence-free survival rates., Results: Indication for surgery was primary mediastinal tumor (n = 55), pleural manifestation (n = 17), or mediastinal recurrence (n = 4) after surgery for thymoma. Early Masaoka-Koga stages I (n = 9) and II (n = 14) shifted to the new stage I (n = 23). Advanced stages III (Masaoka-Koga: n = 20; ITMIG/IASLC: n = 17) and IV (Masaoka-Koga: n = 33; ITMIG/IASLC: n = 35) remained nearly similar and were associated with higher levels of WHO stages. Within each staging system, the survival curves differed significantly with the best 5-year survival in early stages I and II (91%). Survival for stage IV (70 to 77%) was significantly better compared to stage III (49 to 54%). Early stages had a significant longer recurrence-free survival (86 to 90%) than advanced stages III and IV (55 to 56%)., Conclusions: The proportion of patients with IASLC/ITMIG stage I increased remarkably, whereas the distribution in advanced stages III and IV was nearly similar. The new TNM-staging system presents a clinically useful and applicable system, which can be used for indication, stage-adapted therapy, and prediction of prognosis for overall and recurrence-free survival.

Background The working party of the German Society for Surgery (DGCH) on undergraduate surgical education has developed a national expertise-based catalogue of learning goals in surgery (NKLC). This study analyses the extent to which the questions of the German second medical licensing examination compiled by the IMPP are congruent with the NKLC and which thematic focus is emphasised. Materials and Methods Firstly, a guideline and evaluation sheet were developed in order to achieve documentation of the individual examination questions of the second licensing examination with respect to the learning goals of the NKLC. In a retrospective analysis from autumn 2009 to autumn 2014, eleven licensing examinations in human medicine were screened independently by three different reviewers. In accordance with the guideline, the surgical questions were identified and subsequently matched to the learning goals of the NKLC. The analysis included the number of surgical learning goals as well as the number of surgical questions for each examination, learning goal, and different levels of expertise (LE). Results Thirteen reviewers from six surgical disciplines participated in the analysis. On average, reviewers agreed on the differentiation between surgical and non-surgical questions in 79.1% of all 3480 questions from 11 licensing examinations. For each examination (n = 320 questions), 98.8 ± 22.6 questions (min.: 69, max.: 150) were rated as surgical. For each surgical learning goal addressed, 2.2 ± 0.3 questions (min.: 1, max.: 16) were asked. For each examination, 23.5 ± 6.3 questions (min.: 11; max.: 31) referred to learning goals of LE 3, 52.5 ± 16.7 questions (min.: 34; max.: 94) addressed learning goals of LE 2 and 22.8 ± 7.7 questions (min.: 9; max.: 34) were related to learning goals of LE 1. 64 learning goals (27.8% of all learning goals of the NKLC) were not reflected in the examinations. With a total of 70 questions, the most frequently examined surgical topic was "disorders of the rheumatic spectrum". Conclusion The number of surgical examination questions in the German second medical licensing examination seems to be sufficient. However, the questions seem to be unevenly distributed between different surgical areas of undergraduate education. In order to achieve a more homogenous representation of relevant surgical topics, improved alignment is needed between the state examination with existing catalogues of learning goals by the IMPP., Competing Interests: Interessenkonflikt: Die Autoren geben an, dass kein Interessenkonflikt besteht., (Georg Thieme Verlag KG Stuttgart · New York.)

A young patient presented himself to the emergency department with sudden-onset, breathing-dependent right-sided thoracic pain. The auscultation revealed diminished breath sounds on the right. The radiograph showed a pneumothorax which was immediately dealt with chest tube drainage. The CT scan of the thorax showed minuscule subpleural bullae. Video-assisted thoracoscopic surgery (VATS) was performed due to persistent fistulae formation through the drain. The subpleural, bullous and emphysematous changes were histologically confirmed. Investigations into the cause showed evidence of alpha-1-antitrypsin deficiency (AATD). The patient is a Pi MZ type. Few cases of spontaneous pneumothorax as the first manifestation of alpha-1-antitrypsin deficiency have been described. Conclusion: When diagnosing primary spontaneous pneumothorax, alpha-1-antitrypsin deficiency should be considered., Competing Interests: Interessenkonflikt: Die Autoren geben an, dass kein Interessenskonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objectives: Pulmonary arterial hypertension is characterized by pulmonary vascular proliferation and remodelling, leading to a progressive increase in pulmonary arterial resistance. Vasodilator properties of 3 different phosphodiesterase (PDE)-5 inhibitors alone and in combination with an endothelin (ET) receptor antagonist were compared in an ex vivo model., Methods: Segments of human pulmonary arteries (PAs) and pulmonary veins (PVs) were harvested from lobectomy specimens. Contractile forces were determined in an organ bath. Vessels were constricted with norepinephrine (NE) to determine the effects of sildenafil, tadalafil and vardenafil and with ET-1 to assess the effects of bosentan., Results: All 3 PDE-5 inhibitors had no relevant effect on the basal tone of the vessels. Both sildenafil and vardenafil significantly (P < 0.0001) reduced the responses of the vessels to NE, whereas tadalafil was effective only in PA (P = 0.0009) but not in PV (P = 0.097). Sildenafil relaxed NE-preconstricted PV (P < 0.0001) but not PA (P = 0.143). Both tadalafil and vardenafil relaxed PA and PV significantly. Vardenafil appears to be the most potent of the PDE-5 inhibitors tested. Furthermore, we analysed the combination of bosentan and vardenafil in PA. Bosentan and vardenafil reduced ET-1 and NE induced vasoconstriction stronger than vardenafil alone (P ≤ 0.049)., Conclusions: Vardenafil caused the most consistent antihypertensive response in this ex vivo model. However, ET receptor antagonism appears to be an even more potent mechanism. A combination therapy using vardenafil and bosentan turned out to be an effective combination to lower vessel tension in PA., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background  Preoperative radiological assessment is important for clarification of surgical operability for advanced thymic tumors. Objective was to determine the feasibility of magnetic resonance imaging (MRI) with cine sequences for evaluation of cardiovascular tumor invasion. Patients and Methods  This prospective study included patients with advanced thymoma, who underwent surgical resection. All patients received preoperative computed tomography (CT) scan and cine MRI. Results  Tumor infiltration was surgically confirmed in the pericardium ( n  = 12), myocardium ( n  = 1), superior caval vein (SCV; n  = 3), and aorta ( n  = 2). A macroscopic complete resection was possible in 10 patients, whereas 2 patients with aortic or myocardial tumor invasion had R2 resection. The positive predictive value (PPV) was 50% for cine MRI compared with 0% for CT scan regarding myocardial tumor infiltration. The PPV for tumor infiltration of the aorta was 50%, with a higher sensitivity for the CT scan (100 vs. 50%). Infiltration of the SCV could be detected slightly better with cine MRI (PPV 75 vs. 66.7%). Conclusion  Cine MRI seems to improve the accuracy of preoperative staging of advanced thymoma regarding infiltration of cardiovascular structures and supports the surgical approach., (Georg Thieme Verlag KG Stuttgart · New York.)

Therapeutic options to cure advanced, recurrent, and unresectable thymomas are limited. The most important factor for long-term survival of thymoma patients is complete resection (R0) of the tumor. We therefore evaluated the response to and the induction of resectability of primarily or locally recurrent unresectable thymomas and thymic carcinomas by octreotide Long-Acting Release (LAR) plus prednisone therapy in patients with positive octreotide scans. In this open label, single-arm phase II study, 17 patients with thymomas considered unresectable or locally recurrent thymoma (n = 15) and thymic carcinoma (n = 2) at Masaoka stage III were enrolled. Octreotide LAR (30 mg once every 2 weeks) was administered in combination with prednisone (0.6 mg/kg per day) for a maximum of 24 weeks (study design according to Fleming´s one sample multiple testing procedure for phase II clinical trials). Tumor size was evaluated by volumetric CT measurements, and a decrease in tumor volume of at least 20% at week 12 compared to baseline was considered as a response. We found that octreotide LAR plus prednisone elicited response in 15 of 17 patients (88%). Median reduction of tumor volume after 12 weeks of treatment was 51% (range 20%-86%). Subsequently, complete surgical resection was achieved in five (29%) and four patients (23%) after 12 and 24 weeks, respectively. Octreotide LAR plus prednisone treatment was discontinued in two patients before week 12 due to unsatisfactory therapeutic effects or adverse events. The most frequent adverse events were gastrointestinal (71%), infectious (65%), and hematological (41%) complications. In conclusion, octreotide LAR plus prednisone is efficacious in patients with primary or recurrent unresectable thymoma with respect to tumor regression. Octreotide LAR plus prednisone was well tolerated and adverse events were in line with the known safety profile of both agents., Competing Interests: Dr. Kleylein-Sohn, Dr. May and Dr. Baierlein are employees of Novartis. Dr. Boy is an employee of Asclepios clinic. Prof. Schalke reports grants from Novartis within and outside the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The other authors declare no conflicts of interest.

Introduction: Adjuvant platinum-based chemotherapy is standard treatment for surgically resected stage II to IIIA NSCLC, but the relapse rate is high. The preferentially expressed antigen of melanoma (PRAME) tumor antigen is expressed in two-thirds of NSCLC and offers an attractive target for antigen-specific immunization. A phase I dose escalation study assessed the safety and immunogenicity of a PRAME immunotherapeutic consisting of recombinant PRAME plus proprietary immunostimulant AS15 in patients with surgically resected NSCLC (NCT01159964)., Methods: Patients with PRAME-positive resected stage IB to IIIA NSCLC were enrolled in three consecutive cohorts to receive up to 13 injections of PRAME immunotherapeutic (recombinant PRAME protein dose of 20 μg, 100 μg, or 500 μg, with a fixed dose of AS15). Adverse events, predefined dose-limiting toxicity, and the anti-PRAME humoral response (measured by enzyme-linked immunosorbent assay) were coprimary end points. Anti-PRAME cellular responses were assessed., Results: A total of 60 patients were treated (18 received 20 μg of PRAME, 18 received 100 μg of PRAME, and 24 received 500 μg of PRAME). No dose-limiting toxicity was reported. Adverse events considered by the investigator to be causally related to treatment were grade 1 or 2, and most were injection site reactions or fever. All patients had detectable anti-PRAME antibodies after four immunizations. The percentages of patients with PRAME-specific CD4-positive T cells were higher at the dose of 500 μg compared with lower doses. No predefined CD8-positive T-cell responses were detected., Conclusion: The PRAME immunotherapeutic had an acceptable safety profile. All patients had anti-PRAME humoral responses that were not dose related, and 80% of those treated at the highest dose showed a cellular immune response. The dose of 500 μg was selected. However, further development was stopped after negative results with a similar immunotherapeutic in patients with NSCLC., (Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Background: This retrospective study analyzed the effectiveness of intrathoracic negative pressure therapy for debilitated patients with empyema and compared the short-term and long-term outcomes of three different intrapleural vacuum-assisted closure (VAC) techniques., Methods: We investigated 43 consecutive (pre)septic patients with poor general condition (Karnofsky index ≤ 50 %) and multimorbidity (≥ 3 organ diseases) or immunosuppression, who had been treated for primary, postoperative, or recurrent pleural empyema with VAC in combination with open window thoracostomy (OWT-VAC) with minimally invasive technique (Mini-VAC), and instillation (Mini-VAC-Instill)., Results: The overall duration of intrathoracic vacuum therapy was 14 days (5-48 days). Vacuum duration in the Mini-VAC and Mini-VAC-Instill groups (12.4 ± 5.7 and 10.4 ± 5.4 days) was significantly shorter (p = 0.001) than in the group treated with open window thoracostomy (OWT)-VAC (20.3 ± 9.4 days). No major complication was related to intrathoracic VAC therapy. Chest wall closure rates were significantly higher in the Mini-VAC and Mini-VAC-Instill groups than in the OWT-VAC group (p = 0.034 and p = 0.026). Overall, the mean postoperative length of stay in hospital (LOS) was 21 days (median 18, 6-51 days). LOS was significantly shorter (p = 0.027) in the Mini-VAC-Instill group (15.1 ± 4.8) than in the other two groups (23.8 ± 12.3 and 22.7 ± 1.5). Overall, the 30-day and 60-day mortality rates were 4.7 % (2/43) and 9.3 % (4/43), and none of the deaths was related to infection., Conclusions: For debilitated patients, immediate minimally invasive intrathoracic vacuum therapy is a safe and viable alternative to OWT. Mini-VAC-Instill may have the fastest clearance and healing rates of empyema.

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., (Georg Thieme Verlag KG Stuttgart · New York.)

In this review article, state-of-the-art diagnostic tools and innovative treatments of thymoma and thymic carcinoma (TC) are described with special respect to advanced tumour stages. Complete surgical resection (R0) remains the standard therapeutic approach for almost all a priori resectable mediastinal tumours as defined by preoperative standard computed tomography (CT). If lymphoma or germ-cell tumours are differential diagnostic considerations, biopsy may be indicated. Resection status is the most important prognostic factor in thymoma and TC, followed by tumour stage. Advanced (Masaoka-Koga stage III and IVa) tumours require interdisciplinary therapy decisions based on distinctive findings of preoperative CT scan and ancillary investigations [magnetic resonance imaging (MRI)] to select cases for primary surgery or neoadjuvant strategies with optional secondary resection. In neoadjuvant settings, octreotide scans and histological evaluation of pretherapeutic needle biopsies may help to choose between somatostatin agonist/prednisolone regimens and neoadjuvant chemotherapy as first-line treatment. Finally, a multimodality treatment regime is recommended for advanced and unresectable thymic tumours. In conclusion, advanced stage thymoma and TC should preferably be treated in experienced centres in order to provide all modern diagnostic tools (imaging, histology) and innovative therapy techniques. Systemic and local (hyperthermic intrathoracic chemotherapy) medical treatments together with extended surgical resections have increased the therapeutic options in patients with advanced or recurrent thymoma and TC., (© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

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., (Georg Thieme Verlag KG Stuttgart · New York.)

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.

Pseudomyxoma peritonei (PP) is a rare disease characterized by the presence of mucinous ascites and low and progressive accumulation of peritoneal implants. We report the case of a 44-year-old man presented with ascites, imaging evaluations suggesting the diagnosis of gelatinous peritoneal carcinomatosis. The patient underwent laparoscopy with extensive cytoreductive surgery combined with hyperthermic intraoperative peritoneal chemotherapy (HIPEC). Microscopic features confirmed the diagnosis of low-grade PP. Nine months later the patients developed left pleural effusion and cytological examination releaved the intrathoracic extension of PP. The treatment consisted in extensive intrathoracic cytoreductive surgery in combination with hyperthermic intrathoracic chemotherapy perfusion (HITOC). Further surgery was requiered due to intra-abdominal recurrence and finally, the patient developed hepatic and pulmonary metastases treated by systemic chemotherapy, with good tolerability and complete response.

Background: Pulmonary metastases occur in 10-20% of patients with colorectal cancer and significantly influence long-term survival. In this study, the immunological architecture of colorectal lung in comparison to liver metastases and its impact on patient survival were examined., Methods: Specimens of patients with colorectal lung and liver metastases were stained for HE, CD4, CD8, CD20, CD68 and CD45RO. Besides histomorphological evaluation, immunohistochemical stainings were analyzed for the respective cell numbers separately for tumor area, infiltrative margin and distant lung or liver stroma. These findings were correlated with clinical data and patient outcome., Results: In colorectal lung (n = 69) in comparison to liver (n = 222) metastases, the immunological focus is located in the tumor region. A high CD4+ cell infiltration of this area is associated with prolonged survival of patients after resection of colorectal lung metastases [103 ± 33 (high) vs. 37 ± 6 months (low); p = 0.0246]. Patients who were treated with preoperative chemotherapy did not show differences in immune infiltrates compared to chemotherapy-naïve patients., Conclusion: Colorectal lung and liver metastases showed a distinct immunological architecture. A dense cell infiltration of colorectal lung metastases by CD4+ cells was related to prolonged patient survival. Preoperative chemotherapy did not influence cellular immune infiltrates., (© 2016 S. Karger AG, Basel.)

Background: Radical surgical resection of advanced thymic tumors invading either the heart or great vessels facing towards the heart is uncommonly performed because of the potential morbidity and mortality. To achieve a complete tumor resection, the use of cardiolpulmonary bypass (CPB) support might be necessary., Methods: Retrospective analysis of the results in six patients, who underwent radical tumor resection with CBP support., Results: Mean age was 46 years (27 to 66 years) and five patients were male. Tumor infiltration of the heart or the great vessels was evident in all patients. Five patients underwent induction therapy. Two patients were operated in complete cardioplegic arrest (antegrade cerebral perfusion: n = 1). Arterial cannulation of the ascending aorta (n = 5) or the femoral artery (n = 1) and venous cannulation of the right atrium (n = 4) or the femoral vein (n = 2) were performed. Resection of the left brachiocephalic vein (n = 6), resection of the superior caval vein (n = 2), the ascending aorta (n = 1) and the complete aortic arch with outgoing branches (n = 1) were performed. A macroscopic complete resection (R0/R1) was achieved in five patients, whereas one patient was resected incompletely (R2). In-hospital mortality was 0 %. Three (50 %) patients needed operative revision (hematothorax: n = 2, chylothorax: n = 1). All patients had a complicated postoperative course and developed respiratory insufficiency., Conclusions: Locally advanced thymoma/thymic carcinoma invading the heart or great vessels can be treated with radical surgical resection alongside with increased perioperative morbidity. The usage of CBP improves the chance of complete tumor resection in selected patients and might lead to a prolonged survival.

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., (Georg Thieme Verlag KG Stuttgart · New York.)

Objectives: This prospective study is an evaluation of the mini-open vacuum-assisted closure with instillation (Mini-VAC-Instill) therapy for the treatment of complicated pleural empyema., Methods: We investigated septic patients in poor general physical condition (Karnofsky index ≤50%) with multimorbidity and/or immunosuppression who were treated by minimally invasive intrathoracic VAC-Instill therapy without the insertion of an open-window thoracostomy (OWT) between December 2012 and November 2014. All patients underwent mini-thoracotomy with position of a tissue retractor, surgical debridement and local decortication. Surgery was followed by intrathoracic vacuum therapy including periodic instillation using antiseptics. The VAC dressings were changed under general anaesthesia and the chest wall was closed during the same hospital stay. All patients received systemic antibiotic therapy., Results: Fifteen patients (13 males, median age: 71 years) underwent intrathoracic Mini-VAC-Instill dressings for the management of pleural empyema without bronchopleural fistula. The median length of vacuum therapy was 9 days (5-25 days) and the median number of VAC changes per patient was 1 (1-5). In-hospital mortality was 6.7% (n = 1) and was not related to Mini-VAC-Instill therapy or intrathoracic infection. Control of intrathoracic infection and closure of the chest cavity was achieved in 85.7% of surviving patients (12 of 14). After the follow-up at an average of 13.2 months (range, 3-25 months), we observed recurrence once, 21 days after discharge. Two patients died in the late postoperative period (Day 43 and Day 100 after discharge) of fulminant urosepsis and carcinoma-related multiorgan failure, respectively. Analysis of the follow-up interviews in the outpatient clinic showed a good quality of life and a subjectively good long-term aesthetic result., Conclusions: Mini-VAC-Instill therapy is an upgrade of Mini-VAC, which guarantees the advantage of an open treatment, including flushing but without OWT. This procedure is minimally invasive, highly compatible especially with patients in poor general condition and may be an alternative to the OWT in selected patients. Consequently, a very short course of therapy results in good patient acceptance., (© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Video-assisted thoracoscopic surgery (VATS) has revolutionized the practice of thoracic surgeons and improved patient experiences and outcomes worldwide. The VATS approach has matured over the past decades and now accounts for approximately 50 % of all operations in specialized thoracic surgery units. The VATS procedure is less invasive and therefore allows a faster recovery of patients. Over the last 20 years VATS has developed into a safe and effective technique for the diagnostics and therapy of many thoracic diseases. With increasing experience thoracic surgeons can carry out more advanced and technically challenging interventions. Nowadays, VATS is the superior technique in many cases of thoracotomy.

Enthusiasm for minimally invasive thoracic surgery is increasing. Thoracoscopy plays a significant therapeutic role in the fibrinopurulent stage (stage II) of empyema, in which loculated fluid cannot often be adequately drained by chest tube alone. For some debilitated and septic patients, further procedures such as open-window thoracostomy (OWT) with daily wound care or vacuum-assisted closure (VAC) therapy are necessary. In the present article, we propose a new option of minimally invasive VAC therapy including a topical solution of the empyema without open-window thoracostomy (Mini-VAC-instill). Three patients who underwent surgery using this technique are also presented. The discussion is focused on the advantages and disadvantages of the approach., (© The Author(s) 2014.)

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., (Georg Thieme Verlag KG Stuttgart · New York.)

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.

Objectives: The effects of cisplatin on the lung parenchyma during hyperthermic intrathoracic chemotherapy perfusion have not been analysed in detail. The objective of this study was to evaluate both the concentration and depth of the penetration of cisplatin in human lung tissue after hyperthermic exposure under ex vivo conditions., Methods: This experimental study was approved by the local ethics committee. Twelve patients underwent pulmonary wedge resections after elective thoracic lobectomies were performed (resected lobe), and the lung tissue (approximately 1-2 cm(3)) was incubated (in vitro) with cisplatin (0.05 mg/ml; 60 min, 42°C). Subsequent tissue beds (depth, 0.5 mm; median weight, 70-92 mg) were prepared from the outside to the middle, and the amount of cisplatin per tissue weight was analysed using atomic absorption spectrometry. Afterwards, the penetration of cisplatin depth was calculated and related to the different concentrations per tissue., Results: Cisplatin penetrated into the human lung tissue after ex vivo hyperthermic exposure. The median amount of platinum [nmol cisplatin/g lung tissue] decreased significantly (P ≤ 0.05) depending on the penetration depth: 32 nmol/g (1 mm), 20 nmol/g (2 mm) and 6.8 nmol/g (4 mm). The calculated median concentrations of cisplatin (µg/ml) were 2.4 µg/ml (1 mm), 1.4 µg/ml (2 mm) and 0.5 µg/ml (4 mm), respectively., Conclusions: Under ex vivo hyperthermic conditions, cisplatin diffused into human lung tissue. The median penetration depth of the cisplatin was approximately 3-4 mm. The penetration of cisplatin into lung tissue may affect the local therapy of residual tumour cells on the lung surface using hyperthermic intrathoracic chemotherapy perfusion in patients with malignant pleural tumours., (© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Glycated proteins (advanced glycation endproducts, AGE) in tissue are associated with degenerative diseases. This study evaluated the role of sRAGE (soluble receptor for advanced glycation endproducts), a decoy receptor of AGEs in blood, for the outcome of patients after coronary artery bypass grafting (CABG)., Methods: A total of 90 patients undergoing CABG were analysed in two centres. Perioperative blood samples were collected before surgery up to 1 week postoperatively. sRAGE was measured by ELISA. Patients were subdivided regarding age (< 64 versus > 70 years, 14 % versus 35 % female), euroSCORE (< 3 versus > 4, 14 % versus 29 % female) and sRAGE changes between sternotomy and end of the operation (< 30 % versus > 45 %, 33 % versus 33 % female) and subsequently analysed with respect of postoperative outcome parameters., Results: Preoperative sRAGE values did not correlate with the outcome of the patients. sRAGE levels increase within 10 min from 1,539 ± 96 to 5,311 ± 187 pg/ml after sternotomy, then returning to baseline levels within 2 days after surgery. Comparing the analysed possible risk factors age, euroSCORE and sRAGE changes, no difference was observed regarding 30-day mortality. Age and the euroSCORE are superior with respect of tachyarrythmia, whereas sRAGE kinetics seems to be superior with respect of prolonged postoperative respiration time/stay in the intensive care unit or catecholamine support., Conclusion: A prolonged, increased intraoperative sRAGE level is a new outcome predictor for patients undergoing CABG surgery, mutually complementary to the euroSCORE.

Background: Despite significant advances in the treatment of thoracic infections, complex lung abscess remains a problem in modern thoracic surgery. We describe the novel application of vacuum-assisted closure for the treatment of a lung abscess. The technical details and preliminary results are reported., Methods: After the initial failed conservative treatment of an abscess, minimally invasive surgical intervention was performed with vacuum-assisted closure. The vacuum sponges were inserted in the abscess cavity at the most proximal point to the pleural surface. The intercostal space of the chest wall above the entering place was secured by a soft tissue retractor. The level of suction was initially set to 100 mm Hg, with a maximum suction of 125 mm Hg. The sponge was changed once on the 3rd postoperative day., Results: The abscess cavity was rapidly cleaned and decreased in size. The mini-thoracotomy could be closed on the 9th postoperative day. Closure of the cavity was simple, without any short- or long-term treatment failure. This technique reduced the trauma associated with the procedure. The patient was discharged on the 11th postoperative day., Conclusions: Vacuum-assisted closure systems should be considered for widespread use as an alternative option for the treatment of complicated pulmonary abscess in elderly, debilitated, immunocompromised patients after failed conservative treatment.

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., (Georg Thieme Verlag KG Stuttgart · New York.)

Objective: Pain after thoracotomy is associated with intense discomfort leading to impaired pulmonary function., Design: Prospective, non-randomized trial from April 2009 to September 2011., Setting: Department of Thoracic Surgery, single-center., Participants: Thoracic surgical patients., Interventions: Comparison of thoracic epidural analgesia (TEA) with the On-Q® PainBuster® system after thoracotomy., Measurements and Main Results: The TEA group (n=30) received TEA with continuous 0.2% ropivacaine at 4 mL-to-8 mL/h, whereas Painbuster® patients (n=32) received 0.75% ropivacaine at 5 mL/h until postoperative day 4 (POD4). Basic and on-demand analgesia were identical in both groups. Pain was measured daily on a numeric analog scale from 0 (no pain) to 10 (worst pain) at rest and at exercise. There were no significant differences regarding demographic and preoperative data between the groups, but PainBuster® patients had a slightly lower relative forced expiratory volume in 1 second (FEV1) (71±20% versus 86±21%; p=0.01). Most common surgical procedures were lobectomies (38.8%) and atypical resections (28.3%) via anterolateral thoracotomy. Most common primary diagnoses were lung cancer (48.3%) and tumor of unknown origin (30%). At POD1, median postoperative pain at rest was 2.1 (1; 2.8) in the TEA group and 2 (1.5; 3.8; p=0.62) in the PainBuster® group. At exercise, median pain was 4.3 (3.5; 3.8) in the TEA group compared to 5.0 (4.0; 6.5; p=0.07). Until POD 5 there were decreases in pain at rest and exercise but without significant differences between the groups., Conclusions: Sufficient analgesia after thoracotomy can be achieved with the intercostal PainBuster® system in patients, who cannot receive TEA., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Macroscopic cytoreductive surgery and hyperthermic intrathoracic chemotherapy perfusion (HITHOC) is a new multimodal approach for selected patients with primary and secondary pleural tumors, which may provide the patient with better local tumor control and increased overall survival rate., Methods: We present a single-center study including 20 patients undergoing cytoreductive surgery and HITHOC between September 2008 and April 2013 at the University Medical Center Regensburg, Germany. Objective of the study was to describe the perioperative, anaesthetic management with special respect to pain and complication management., Results: Anaesthesia during this procedure is characterized by increased intrathoracic airway and central venous pressure, hemodynamic alterations and the risk of systemic hypo- and hyperthermia. Securing an adequate intravascular volume is one of the primary goals to prevent decreased cardiac output as well as pulmonary edema. Transfusion of packed red blood cells (PRBC) was necessary in seven of 20 (35%) patients. Only two patients (10%) showed an impairment of coagulation in postoperative laboratory analysis. Perioperative forced diuresis is recommended to prevent postoperative renal insufficiency. Supplementary thoracic epidural analgesia in 13 patients (65%) showed a significant reduction of post-operative pain compared with peroral administration of opioid and non-opioid analgesics., Conclusion: This article summarizes important experiences of the anaesthesiological and intensive care management in patients undergoing HITHOC.

Tumor xenografts in immunodeficient mice, while routinely used in cancer research, preclude studying interactions of immune and cancer cells or, if humanized by allogeneic immune cells, are of limited use for tumor-immunological questions. Here, we explore a novel way to generate cancer models with an autologous humanized immune system. We demonstrate that hematopoietic stem and progenitor cells (HSPCs) from bone marrow aspirates of non-metastasized carcinoma patients, which are taken at specialized centers for diagnostic purposes, can be used to generate a human immune system in NOD-scid IL2rγ(null) (NSG) and HLA-I expressing NSG mice (NSG-HLA-A2/HHD) comprising both, lymphoid and myeloid cell lineages. Using NSG-HLA-A2/HHD mice, we show that responsive and self-tolerant human T cells develop and human antigen presenting cells can activate human T cells. As critical factors we identified the low potential of bone marrow HSPCs to engraft, generally low HSPC numbers in patient-derived bone marrow samples, cryopreservation and routes of cell administration. We provide here an optimized protocol that uses a minimum number of HSPCs, preselects high-quality bone marrow samples defined by the number of initially isolated leukocytes and intra-femoral or intra-venous injection. In conclusion, the use of diagnostic bone marrow aspirates from non-metastasized carcinoma patients for the immunological humanization of immunodeficient mice is feasible and opens the chance for individualized analyses of anti-tumoral T cell responses.

Background: In cases of intravenous placement failure of the left ventricular (LV) lead for cardiac resynchronisation therapy (CRT) and obliteration of the left pleural space, the alternative approach of transthoracic placement by video-assisted thoracoscopic surgery (VATS) is difficult and not commonly practiced., Methods: Here, we present a simple technique for transthoracic introduction of an epicardial LV lead using a wound retractor (ALEXIS) in a patient with heart failure. This wound retractor enables atraumatic tissue retraction without rib spreading, an optimal direct view in the pleural space for surgical pleurolysis and a high degree of safety for the patient., Results: No perioperative complications occurred. The tube drainage was removed on the second postoperative day, and the patient was discharged on the third postoperative day., Conclusions: The decided advantage of this new method is the lack of any need for rib spreading using a mechanical retractor. Especially in patients with a history of open-heart surgery (including internal mammary artery bypass grafting and/or revascularisation of the left lateral wall) or known pleural adhesions (e.g., pleuritis or lung operations), the described technique provides a rapid and save access with minimal surgical effort and greater safety.