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Pleuroperitoneal leakage with the formation of hydrothorax is a rare complication of peritoneal dialysis, usually necessitating termination of peritoneal dialysis. We hypothesized that implantation of a polypropylene mesh on the diaphragm using video-assisted thoracoscopic surgery might induce permanent closure of pleuroperitoneal leakage. We report a case series of n = 12 peritoneal dialysis patients with pleuroperitoneal leakage and right-sided hydrothorax who underwent video-assisted thoracoscopy with mesh implantation from 2011 to 2020. Pleuroperitoneal leakage had been confirmed before surgery by intraperitoneal administration of toluidine blue, contrast-enhanced computer tomography or glucose determination from the pleural effusion. Median time from the start of peritoneal dialysis to manifestation of pleuroperitoneal leakage was 52 days. Video-assisted thoracoscopic surgery revealed multiple penetration points in the tendinous part of the diaphragm in all patients, which appeared as blebs. These were closed by covering the whole diaphragm with a polypropylene mesh. In all patients, peritoneal dialysis was paused for three months and bridged by hemodialysis. After restarting peritoneal dialysis and a median follow-up time of 1.9 years, none of the patients experienced a recurrence of pleuroperitoneal leakage. This case series demonstrates that pleuroperitoneal leakage in peritoneal dialysis patients can be permanently closed using thoracoscopic mesh implantation and allows peritoneal dialysis to be continued as renal replacement therapy. Graphical abstract

Background Recurrent ventricular tachycardia (VT) can occur after left ventricular assist device (LVAD) implantation. In this case, medical treatment might be insufficient. We report a case of a left-sided thoracoscopic sympathectomy as a feasible treatment escalation in intractable VT. Case report A 72-year-old patient underwent an internal cardioverter defibrillator (ICD) implantation as primary prophylaxis for VTs in the setting of staged heart failure therapy. Afterwards, due to a progressive dilative cardiomyopathy he underwent a minimal-invasive LVAD implantation (HeartWare, Medtronic). After an uneventful minimal-invasive LVAD-implantation the patient was discharged to a rehabilitation program. However, after 7 weeks he developed recurrent VTs which were successfully terminated by ICD shocks deliveries leading to severe discomfort and frequent hospitalizations. Eventually, the patient was admitted with an electrical VT storm. Successful endocardial catheter ablation of all inducible VTs were performed combined with multiple rearrangements of his oral antiarrhythmic medication. However, all these treatments could not suppress further occurrence of VTs. After an interdisciplinary discussion the patient agreed to a left-sided video-assisted thoracoscopic sympathectomy. After a follow up of 150 days the patient was free from VTs apart from one short event. Conclusion We believe video-assisted thoracoscopic sympathectomy might be a surgical treatment option in patients with intractable recurrent VTs after catheter ablation of VT reentrant substrate even after minimal-invasive LVAD implantation.

Background No consensus regarding the best post-operative treatment option for air leak has been established. In this study, we evaluate the use of intra-pleural fresh frozen plasma (FFP) as a promising treatment method. Methods Treatment for a sustained air leak (3 days) was warranted in approximately 12% of the lung surgeries at our institution. Fifty-two patients were treated with FFP by application of 250 mL daily. The patients were divided into two cohorts: cohort 1 consisted of 35 patients undergoing anatomical lung resections and cohort 2 consisted of 17 patients after miscellaneous types of lung surgery. Successfulness of the procedure as well as the potential influential factors was evaluated statistically and validated by a bootstrapping. Area under receiver operating characteristic curve was used to establish a cut-off value of the predictor. Results In the first cohort, air leakage was successfully treated in 28 (80%), while in seven (20%) it was still present after third treatment with FFP. The success rate in cohort 2 was 76.5%. The only covariate which appeared to remain significant in both cohorts was flow as displayed on the digital suction device prior to application of FFP. Flow ≤375 mL/min was indicative of successful aerostasis. Conclusion Intra-pleural instillation of FFP seems to be a feasible method for the treatment of post-operative air leakage. Although the optimum strategy regarding its application as well as its limitations is yet to be established, an absence of complications or undesirable events makes this (off label) method a safe and promising alternative to existing options.

Simple Summary Peripheral nerve sheath tumors are associated with significant morbidity. Clinical presentation, tumor location, and therapeutic strategies are variable. We aim to provide high-quality data concerning the results of interdisciplinary operative approaches for surgical resection of schwannomas. Understanding the anatomical and functional challenges of surgical interventions in the peripheral nervous system can help to enhance the outcomes of these therapies. We aim to highlight the need for interdisciplinarity and provide evidence for both excellent functional outcomes, as well as improved quality of life for patients undergoing sporadic schwannoma surgery. Abstract Most sporadic peripheral nerve sheath tumors in adults are schwannomas. These tumors usually present with significant pain but can also cause neurological deficits. Symptomatology is diverse, and successful surgical interventions demand interdisciplinarity. We retrospectively reviewed 414 patients treated between 2006 and 2017 for peripheral nerve sheath tumors. We analyzed clinical signs, symptoms, histology, and neurological function in the cohort of adult patients with schwannomas without a neurocutaneous syndrome. In 144 patients, 147 surgical interventions were performed. Mean follow-up was 3.1 years. The indication for surgery was pain (66.0%), neurological deficits (23.8%), significant tumor growth (8.8%), and suspected malignancy (1.4%). Complete tumor resection was achieved on 136/147 occasions (92.5%). The most common location of the tumors was intraspinal (49.0%), within the cervical neurovascular bundles (19.7%), and lower extremities (10.9%). Pain and neurological deficits improved significantly (p ≤ 0.003) after 131/147 interventions (89.1%). One patient had a persistent decrease in motor function after surgery. Complete resection was possible in 67% of recurrent tumors, compared to 94% of primary tumors. There was a significantly lower chance of complete resection for schwannomas of the cervical neurovascular bundle as compared to other locations. The surgical outcome of sporadic schwannoma surgery within the peripheral nervous system is very favorable in experienced peripheral nerve surgery centers. Surgery is safe and effective and needs a multidisciplinary setting. Early surgical resection in adult patients with peripheral nerve sheath tumors with significant growth, pain, neurological deficit, or suspected malignancy is thus recommended.

Background and study aims: Management of esophago-jejunal anastomotic leakages (EJAL) following gastrectomy is challenging. Endoscopic negative pressure therapy (ENPT) is an emerging effective tool for treatment of gastrointestinal and anastomotic leaks. We have been using ENPT as first line therapy for EJAL after oncological gastric resections since 2018. The aim of the study was to present our results with this strategy in a case series. Methods: Nine consecutive patients were treated with ENPT for EJAL after oncological gastrectomy between 01.2018 and 12.2019. A retrospective analysis of patients’ and treatment-related data was performed. Results: Time to leakage detection was 6.00 ± 2.49 days after surgery. After 14.78 ± 9.66 days of ENPT, 6.25 ± 3.65 endoscopies and 38.11 ± 16.46 days of hospitalization, endoscopic treatment with ENPT combined with surgical debridement and drainage for sepsis control was effective in eight of nine patients. In one patient with a complete anastomotic dehiscence, treatment was changed to a stent-based therapy combined with surgery. Conclusions: ENPT is a new and promising option in the complication management of patients with anastomotic insufficiencies following oncological gastrectomy. It can be recommended in combination with limited surgery to preserve the anastomosis and provide sepsis control. The time interval to diagnosis and the size of the insufficiency are important for the success of ENPT in patients with EJAL.

The aim was to evaluate the incidence of stroke in the setting of cardiac surgery with or without hemodynamically relevant asymptomatic carotid stenosis contralateral to the occlusion. We designed a historical cohorts study, focused on patients with unilateral totally occluded internal carotid arteries who were referred for any cardiac surgery at our center. Isolated unilateral occlusions were assigned to group 1 (n = 60), and those with a contralateral stenosis grade ≥ 60% were included in group 2 (n = 51). A total of 111 patients operated in our center from 1997 to 2016 were included. Patients in group 2 had an asymptomatic contralateral internal carotid artery stenosis with a mean stenosis grade of 71 ± 20%. Simultaneous carotid endarterectomy (CEA) was performed in 22 patients from group 2. The overall mortality was 8/111 (7.2%). Carotid-associated mortality was not observed, whereas an overall stroke incidence of 8/111 (7.2%) was detected. The group-related outcome showed comparable results for mortality (group 1: 4/60 (6.7%) vs. group 2: 4/51 (7.8%); p = 1.0). Regarding stroke incidence, group 2 had a higher incidence of overall strokes (2/60 (3.3%) vs. 6/51 (11.8%); p = 0.14) with more contralateral (0/60 (0%) vs. 2/51 (3.9%); p = 0.209) and ipsilateral strokes (2/60 (3.3%) vs. 4/51 (7.8%); p = 0.411). Stroke rate peaked in patients with simultaneous carotid and cardiac surgery (n = 22; 18.2%; p = 0.048). Performing simultaneous CEA during cardiac surgery in the presence of a contralateral occlusion may promote stroke. Asymptomatic contralateral carotid stenosis is a risk factor for stroke in patients with carotid occlusion prior to cardiac surgery.

We would like to thank G. Rossi et al. for their interest and taking the time to comment on our manuscript "Cryobiopsy increases the EGFR detection rate in non-small cell lung cancer”.

Cotton-based surgical invasive devices with their desired hemostyptic properties have been used for decades in the surgical field. However, in cardiac surgery using the heart-lung machine with direct retransfusion of suction blood, activated blood may re-enter the circulation without filtration and may trigger a cascade reaction leading to systemic inflammation and thrombosis. We therefore set out to evaluate the inflammatory potential of untreated and pyrogen-impregnated cotton-based surgical invasive medical devices. After incubation of the swabs with whole blood or PBMC, the cell-free supernatant was investigated for IL1β and IL6. While the reaction of human whole blood toward cotton swabs could not be influenced by any sterilization technique, dry heat and gamma-irradiation were able to diminish the inflammatory reaction of PBMC toward the material and the used pyrogens. In conclusion, using PBMC in direct contact to cotton we are the first to establish a suitable test method for quantification of the pyrogenic/inflammatory activity of this material. The unaltered reaction of whole blood, however, suggests a crosstalk of cells and plasma proteins in the inflammation activation that is not prevented by sterilization of the swabs. This new in vitro testing methodology may help to better display the clinical situation during development of new materials. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1877-1888, 2019.

Background and objectives The role of local surgical procedures in patients with metastatic soft tissue sarcoma is still undefined. Few retrospective studies have reported survival benefits for patients with pulmonary metastases after complete surgical resection. Treatment decisions are therefore mainly based on personal experiences rather than on reproducible knowledge. Method A total of 237 patients with metastatic sarcoma, treated between 1982 and 2015 at the University Hospital Tuebingen, Germany, were eligible for inclusion. Out of the 237 screened patients, 102 patients underwent at least one metastasectomy. Overall survival was defined as the primary endpoint in this study. For association of non-linear relationship to the endpoint, significant prognostic factors were included into a recursive partitioning model. A subgroup analysis for long-term survivors was also performed. Results The median overall survival was 64 months. The 3-, 5-, 10-, and 20-years overall survival rates were 70.7%, 50.3%, 24.7%, and 14.8%, respectively. The number of resections and the progression-free intervals were independent prognostic factors in three statistical models. Conclusion Repeated resections of metastases from different localizations are a strong predictor for prolonged survival. We suggest that the progression-free interval after metastasectomy should be considered as a predictive factor for benefit from further surgery.

Minimally invasive surgery in some cases suffers from a limited view because certain areas are obscured by others. In this paper, a system is described, which can be used in minimally invasive procedures as an addition to a standard endoscope to improve the range of view. Through FEM simulation a magnetic circuit was designed to position the camera head. Subsequently, a camera positioning system was set up that includes an extracorporeal and an intracorporeal unit. The first controls the intracorporeal system. The latter has a camera inclination angle of up to 65° and an additional vertically downward viewing angle when aligned in parallel (inclination angle 0°). The panning angle is 360°. The camera system was evaluated in lab and cadaver trials. It has been found that the size of the intracorporeal system (16 × 10 × 150 mm) represents a major problem. Future work will focus of the reduction of the system’s size, the improvement of the camera image quality, and design changes considering mechanical stability.

Objectives: Detection of activating epidermal growth factor receptor (EGFR) mutation is crucial for individualized treatment of advanced non-small-cell lung cancer (NSCLC). However little is known about how biopsy technique affects the detection rate of EGFR mutations. This retrospective, single center study evaluated the detection rate of EGFR mutations in tissue obtained by bronchoscopic cryobiopsy and compared this to other standard tissue sampling techniques. Materials and methods: We retrospectively analyzed 414 patients with histologically confirmed NSCLC and known EGFR mutation status between 3/2008-7/2014. Tumor specimens obtained by tissue preserving bronchoscopic cryobiopsy were compared to those obtained by other techniques. Results and conclusion: Analysis of bronchoscopic cryobiopsy tissue detected 29 activating EGFR mutations in 27 (21.6 ) out of 125 patients, while analysis of tissue obtained by non-cryobiopsy techniques (bronchoscopic forceps biopsies, fine needle aspiration, imaging guided transthoracical and surgical procedures) detected 42 EGFR mutations in 40 (13.8 ) out of 298 patients (p < 0.05). Cryobiopsy increased detection rate of EGFR mutations in central tumors compared with forceps biopsy (19.6 versus 6.5 , p < 0.05), while an insignificant trend was detected also for peripheral tumors (33.3 versus 26.9 ). Bronchosopic cryobiopsy increases the detection rate of activating EGFR mutations in NSCLC in comparison to other tissue sampling techniques. This will help to optimize individualized treatment of patients with advanced tumors. Because of the retrospective nature of this analysis, a prospective trial is mandatory for final assessment. © 2020 The Author(s)

OBJECTIVES Video-assisted thoracic surgery (VATS) is a complex technique requiring dedicated surgical training. Platforms for such training are scarce and often rely on the use of live animals, which raises ethical concerns. The objective of this study was to develop a box trainer that is dedicated for VATS training and able to reproduce bleeding scenarios. METHODS The developed Tuebingen Thorax Trainer comprises 5 components that are mounted on a human anatomy-like thoracic cavity containing a porcine organ complex. Any standard thoracoscopic instrument can be used. The organ complex is attached to a perfusion module. We assessed the applicability of the system in four 1-day VATS training courses at the Tuebingen Surgical Training Center. Assessment was performed using a questionnaire handed out to all participants. RESULTS Forty participants have been trained with the Tuebingen Thorax Trainer at our institution since November 2016. Thirty-five (87.5%) participants stated that the Tuebingen Thorax Trainer is an adequate model for VATS training. The ex vivo organ complex was reported to be realistic with regards to the level of detail and scale (76%). A large proportion of participants (27.5%) were experienced with VATS and reported having performed >50 procedures before taking the training course. CONCLUSIONS This new training device allows realistic training for VATS procedures. ‘Stagnant hydrostatic perfusion’ permits simulation of reproducible bleeding scenarios. The device is low in production costs and offers a strong resemblance to the clinical scenario. It reduces the use of animal models and contributes to the efforts in making surgical skills training for VATS more accessible.

Purpose Spontaneous pneumothorax (PNTX) is a common disease frequently operated at specialized thoracic surgery units. Videothoracoscopic surgery (VATS) has become the standard for treatment and recurrence prevention. While there is broad consensus regarding indications and techniques of PNTX surgery, postoperative risks and consecutive patient behavioral advice have not been sufficiently elucidated. Methods Single-center cohort analysis of 641 patients operated for primary PNTX by VATS over 10 years. Putatively recurrence-prone lifestyle activities (smoking status, flying habits, and scuba diving) and actual occurrence of recurrences were correlated. Results Follow-up rate was 46% (279/607 patients). Mean time interval between primary operation and follow-up was 61 (range: 5-177) months. In 10 patients (3.6%), a PNTX recurrence was observed. Regarding postoperative risk behavior reported at follow-up, 28% of patients were active smokers (15 ± 7 cigarettes/day), 59% traveled by plane repeatedly, and only two patients did scuba diving (0.7%). Low body-mass-index was associated with an increase in PNTX recurrence, whereas smoking, flying, and scuba diving could not be identified as risk factors. Conclusion In our study, none of the supposed "classic" lifestyle-associated risk factors for PNTX recurrence after VATS proved to be a significant threat. Postoperative patient behavior might not be constrained by overcautious medical advice.

We report on a patient with acute dyspnea after several vertebral body interventions, among others a kyphoplasty, that was performed a few days earlier.In the computed tomography we prove a bilateral pulmonary embolism (cement and thrombus). There is no right heart failure. A deep vein thrombosis can be excluded by color-coded vascular ultrasound.The pulmonary embolism is due to bone cement. The cement material is also found paravertebral, intraspinal and intraneuroforaminal. By conservative treatment using therapeutic anticoagulation and analgesic medication, the patient showed a rapid clinical improvement.In patients with cardiopulmonary symptoms after vertebroplasty and kyphoplasty, pulmonary embolism due to bone cement should be considered as a possible cause. The therapy depends on the extent of the cement embolism and the symptoms of the patient.

OBJECTIVES: Serum response factor (SRF), E2F1 and survivin are well-known factors involved in a multitude of cancer-related regulation processes. However, to date, no suitable means has been found to apply their potential in the therapy of non-small cell lung cancer (NSCLC). This study deals with questions of small interfering ribonucleic acid (siRNA) transfection efficiency by a non-viral transfection of NSCLC cell-lines and the power of siRNA to transiently influence cell division by specific silencing. METHODS: Different NSCLC cell lines were cultured under standard conditions and transfected, with specific siRNA targeting SRF, E2F1 and survivin in a non-viral manner. Cells treated with non-specific siRNA (SCR-siRNA) served as controls. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed for messenger RNA (mRNA) expression levels. Additionally, transfection efficiency was evaluated by flow cytometry. The analysis of cell proliferation was determined with a CASY cell counter 3 days after transfection with SRF or SCR-siRNA. RESULTS: Transfection of the NSCLC cell lines with specific siRNAs against SRF, E2F1 and survivin resulted in a very considerable reduction of the intracellular mRNA concentration. CASY confirmation of cell viability demonstrated an excellent survival of the cell lines treated with non-specific siRNA, in contrast to with application of specific siRNA. CONCLUSIONS: This study reports a reliable transfectability of NSCLC-cell lines by siRNA, initially in a non-viral manner, and a reproducible knockdown of the focussed targets, consequently leading to the death of the tumour cells. This constitutes a strong candidate for a new assessment strategy in the therapy of non-small cell lung cancer.

The standard treatment for stage I non-small cell lung cancer (NSCLC) is lobectomy. However, a considerable number of patients are not eligible for standard lung surgery due to poor pulmonary function or comorbidities. We evaluated the efficacy and tolerability of intensity-modulated stereotactic radiotherapy (IMSRT) with moderate hypofractionation for these patients. Twelve patients were selected for IMSRT. 4D-CT planning was performed by gating CT-scanning positioning. The applied doses ranged between 10x4.5 Gy (80% ID) (N=1), 12x4.5 Gy (95% ID) (N=1) and 10x5.5 Gy (95% ID) (N=10). Long-term follow-up was performed including spirometry and CT for evaluation of local, locoregional and distant control. Even in patients with poor pulmonary function IMRST was safe and well tolerated. No severe acute adverse effects were observed. Estimated local control at 2 years was 90%. Moreover, IMSRT does not induce a significant deterioration of pulmonary function. IMRST is safe and feasible even for patients with very poor pulmonary function. The applied dose provides a high local control rate, although the biological equivalent dose (BED) is lower compared to the average of other SRT regimens. Therefore, IMRST may be an efficient alternative for all NSCLC stage I patients with contraindications to standard lobectomy especially in patients with small tumors in high-risk localisations.

Der Indikation fur eine Thoraxdrainage als isolierte Masnahme liegt eine Raumforderung im Pleuraspalt zugrunde. Die Qualitat der Raumforderung ist dabei entweder flussig (Erguss, Blut, Eiter, Spulflussigkeit), gasformig (Pneumothorax) oder beides (Empyem). Bei dynamischer Progredienz kann es zu lebensbedrohlichen Spannungszustanden (Spannungspneumothorax, Mediastinalshift, Cavakompressionssyndrom) kommen. Die Thoraxdrainage muss unter erheblichem Zeitdruck, in ungewohnter Lage und ungewohnter Umgebung sicher gelegt werden konnen. Es ist deshalb unabdingbar, die folgenden Schritte absolut sicher zu beherrschen.

OBJECTIVES: Lung cancer is the leading cause of death in cancer statistics throughout developed countries. While single surgical approach provides best results in early stages, multimodality approaches have been employed in advanced disease and demonstrated superior results in selected patients. With either full-dose chemotherapy and/or radiotherapy, patients usually have a poor general condition when entering surgical therapy and therefore neoadjuvant therapy can lead to a higher morbidity and mortality. Especially in the case of pneumonectomy as the completing procedure, mortality rate can exceed over 40%. Therefore, chest physicians often shy away from recommending pneumonectomy as final step in trimodal protocols. We analysed our experience with pneumonectomy after neoadjuvant chemoradiotherapy in advanced non-small-cell lung cancer (NSCLC) with a focus on feasibility, outcome and survival. METHODS: Retrospective, single-centre study of 146 patients with trimodal neoadjuvant therapy for NSCLC Stage III over 17 years time span. Follow-up was taken from our own outpatient files and with survival check of central registry office in Baden-Wurttemberg, Germany. RESULTS: A total of 118 men and 28 women received 62 lobectomies, 6 bi-lobectomies and 78 pneumonectomies after two different neoadjuvant protocols for Stage III NSCLC. Overall morbidity rate was 53 and 56% after pneumonectomy. Overall hospital mortality rate was 4.8 and 6.4% after pneumonectomy. Overall median survival rate was 31 months with a 5-year survival rate of 38% (Kaplan– Meier). Pneumonectomy, right-sited pneumonectomy and initial T- and N-stages were no risk factors for survival (log-rank test). Significant factors for survival were ypT-stage, ypN-stage, yUICC-stage in univariate testing (log-rank test) and ypUICC-stage in multivariate testing (Cox’s regression). CONCLUSIONS: Pneumonectomy in neoadjuvant trimodal approach for Stage III NSCLC can be done safe with acceptable mortality rate. Patients should not withhold from operation because of necessitating pneumonectomy. Not the procedure but the selection, response rate and R0-resection are crucial for survival after trimodal therapy in experienced centres.

The prognosis of bronchogenic carcinoma in stage III N2 is poor. Five-year survival ranges between 0 and 5%. Lymph-node involvement itself still is the main prognostic factor. Complete lymphadenectomy improves long-term survival in contrast to lymph-node sampling. Recent studies have indicated that the number of involved lymph nodes could be another prognostic factor. It has also been proved that complete lymphadenectomy is necessary for correct staging. This also applies to preoperative staging prior to neoadjuvant treatment. For this reason exact knowledge of lymph-node anatomy and drainage is required. To achieve assessment and comparison of mediastinal staging and of lymphadenectomy, the number of pathologically examined lymph nodes should be documented. Other prognostic factors within N2 stages are age and T stage. Molecular markers are subject to major investigation. A definite clinical relevance, however, could so far not be verified for any of them.

Objectives: Spontaneous pneumothorax (PTX) is a common disease frequently operated at specialized thoracic surgery units. It may arise in adolescents with healthy lung tissue (primary PTX) or in elder patients with preexisting lung disease (secondary PTX). Videothoracoscopic surgery (VATS) has become the surgical standard for treatment and recurrence prevention. While there is broad consensus regarding indications and techniques of PTX surgery, potential postoperative risks and consecutive patient behavioral advice have not been sufficiently elucidated to date. Methods: Single-center cohort analysis of 646 patients operated for primary PTX by VATS over a time period of 10 years. Putatively recurrence prone lifestyle activities (smoking status, flying habits, scuba diving) and actual occurrence of recurrences were correlated. Results: Follow up rate was 43% (279/646 patients). Mean time interval between primary operation and follow up was 61 (range 5–177) months. In 10 patients (3.6%), a PTX recurrence was observed. Regarding postoperative risk behavior reported at follow-up, 28% of patients were active smokers (in average 15 ± 7 cigarettes/day), 59% travelled by plane repeatedly, and only 2 patients did scuba diving (0.7%). Neither smoking nor flying or scuba diving could not be identified as statistically significant risk factors for PTX recurrence. Conclusions: In our study, none of the supposed “classic” lifestyle-associated risk factors for PTX recurrence after VATS proved to be a significant threat. Thus, postoperative patient behavior might not necessarily be constrained by overcautious medical advice.

OBJECTIVES: According to the actual treatment strategies of lung cancer, the current therapeutic regimen is an individualized, multidisciplinary concept. The development of chemoresistance in the last decade represents the most important obstacle to an effective treatment. In our study, we examined a new therapeutic alternative in the treatment of multiresistant lung adenocarcinoma via siRNA-specific transfection of six crucial molecules involved in lung carcinogenesis [serum response factor(SFR), E2F1, Survivin, hypoxia inducible factor1 (HIF1), HIF2 and signal transducer and activator of transcription (STAT3)]. METHODS: Three chemoresistant A549 adenocarcinoma cells were cultured under standard conditions at 37°C and 5% CO2. The chemoresistance against Vinflunine, Vinorelbine and Methotrexate was induced artificially. The A549 cells were transfected for 2 h at 37°C with specific siRNA targeting SRF, E2F1, Survivin, HIF1, HIF2 and STAT3 in a non-viral manner. The efficiency of siRNA silencing was evaluated via quantitative real-time polymerase chain reaction, whereas the surviving cells after siRNA transfection as predictor factor for tumoural growth were analysed with a CASY cell counter 3 days after transfection. RESULTS: The response of the chemotherapeutic resistant adenocarcinoma cells after siRNA transfection was concentration-dependent at both 25 and 100 nM. The CASY analysis showed a very effective suppression of adenocarcinoma cells in Vinorelbine, Vinflunine and Methotrexate groups, with significantly better results in comparison with the control group. CONCLUSIONS: In our study, we emphasized that siRNA interference might represent a productive platform for further research in order to investigate whether a new regimen in the treatment of multiresistant non-small-cell lung cancer could be established in vivo in the context of a multimodal cancer therapy.

Anamnese und klinischer Befund: Wir berichten uber einen Patienten mit akuter Dyspnoe nach mehreren Wirbelkorpereingriffen, unter anderem einer Kyphoplastie, die wenige Tage zuvor erfolgte. Untersuchungen: Computertomografisch kann eine eine bilaterale Lungenarterienembolie (Zement und Thrombus) nachgewiesen werden. Der rechte Ventrikel ist nicht belastet. Eine tiefe Beinvenenthrombose kann mittels Farbduplexsonografie ausgeschlossen werden. Diagnose, Therapie und Verlauf: Ursache fur die Lungenembolie ist Knochenzement. Das Material wird zudem paravertebral, intraspinal und intraneuroforaminal gefunden. Unter einer konservativen Therapie mittels therapeutischer Antikoagulation und analgetischer Medikation bessert sich der Patient klinisch rasch. Folgerung: Bei Patienten mit kardiopulmonalen Symptomen nach einer Vertebro- oder Kyphoplastie sollte eine durch Knochenzement vermittelte Lungenarterienembolie in Betracht gezogen werden. Die Therapie richtet sich nach der Symptomatik des Patienten und dem Ausmas der Zementembolie.

e20613Background: Activating mutations in the epidermal growth factor receptor (EGFR) gene are pharmacological targets for EGFR tyrosine kinase inhibitors (TKI) in patients with advanced non-small-...

OBJECTIVES Mediastinoscopy represents the gold standard for invasive mediastinal staging. While learning and teaching the surgical technique are challenging due to the limited accessibility of the operation field, both benefited from the implementation of video-assisted techniques. However, it has not been established yet whether video-assisted mediastinoscopy improves the mediastinal staging in itself. METHODS Retrospective single-centre cohort analysis of 657 mediastinoscopies performed at a specialized tertiary care thoracic surgery unit from 1994 to 2006. The number of specimens obtained per procedure and per lymph node station (2, 4, 7, 8 for mediastinoscopy and 2-9 for open lymphadenectomy), the number of lymph node stations examined, sensitivity and negative predictive value with a focus on the technique employed (video-assisted vs standard technique) and the surgeon's experience were calculated. RESULTS Overall sensitivity was 60%, accuracy was 90% and negative predictive value 88%. With the conventional technique, experience alone improved sensitivity from 49 to 57% and it was predominant at the paratracheal right region (from 62 to 82%). But with the video-assisted technique, experienced surgeons rose sensitivity from 57 to 79% in contrast to inexperienced surgeons who lowered sensitivity from 49 to 33%. We found significant differences concerning (i) the total number of specimens taken, (ii) the amount of lymph node stations examined, (iii) the number of specimens taken per lymph node station and (iv) true positive mediastinoscopies. CONCLUSIONS The video-assisted technique can significantly improve the results of mediastinoscopy. A thorough education on the modern video-assisted technique is mandatory for thoracic surgeons until they can fully exhaust its potential.

A 74-year-old man presented with progressive dyspnea after a 10-days latency following a thoracic trauma. CT imaging showed multiple rib fracture and an empyema that was primarily treated by a chest tube. In the course of the hospital stay, a rapidly progressive paraplegia developed and the MR imaging revealed a peridural abscess caused by a pleural empyema. Due to trauma-related barrier damage and the initial delay of the operative therapy a usually less invasive pathogen (streptococcus intermedius) could affect the peridural space. The successful therapy consisted of urgent laminectomy and a subsequent video-assisted thoracoscopy supported by systemic antibiotic therapy.

OBJECTIVES: Persistent mediastinal lymph node metastasis after neoadjuvant therapy is a significant negative indicator for survival. Even though there is still no consensus on the matter, some authors advocate a thorough restaging prior to surgery and deny surgery in cases of persistent N2 because of the poor outcome. We analysed our results after trimodal therapy in pN2/N3 stage III non-smallcell lung cancer (NSCLC) and persistent mediastinal lymph node metastasis after neoadjuvant chemoradiotherapy. METHODS: We conducted a retrospective cohort analysis of 167 patients who received trimodal therapy for stage III NSCLC. Progression-free interval and survival were calculated. T-stage, N-stage, ypT-stage, ypN2/3-stage and surgical procedure were tested as risk factors. RESULTS: Eighty-three patients with potentially resectable initial pN2/3 underwent 44 pneumonectomies and 76% extended resections. Thirty-five patients showed persistent mediastinal lymph node metastasis after trimodal therapy. Treatment-related comorbidity after an operative therapy was 58%. Hospital mortality was 2.4%. The ypT- and ypN2/N3 stages were significant risk factors and, in the case of persistent mediastinal lymph node metastasis, median progression-free period was 17 months and median survival time was 21 months. CONCLUSIONS: Persistent but resectable N2/N3 after chemoradiotherapy in stage III NSCLC is the least favourable subgroup of patients in neoadjuvant approaches. If surgery can be carried out with curative intent and low morbidity, completing trimodal therapy is justified, with an acceptable outcome.

Background Increasing application of cardiac resynchronization therapy is accompanied by an increase in patients requiring removal of coronary sinus (CS) leads. The aim of this study was to determine outcomes of closed chest CS lead extraction using intravascular dissection devices. Methods Between 2000 and 2011, 41 patients (80.5% men; aged 64.2 ± 13.8 years) underwent transvenous CS lead extraction procedures. Reasons for lead extraction were infection in 9, CS lead dislodgement in 15, lead malfunction, including manufacturer-initiated product recall in 6, phrenic nerve stimulation in 5, combinations of causes in 5, and elective extraction concomitant with generator replacement for battery depletion in 1. Results In addition to 24 isolated CS lead extractions, we performed 17 multiple lead extractions (2 to 4 leads) after a mean of 30.6 ± 32.5 months. The time elapsed from implantation was 4.6 ± 9.1 months for isolated CS and 42.6 ± 32.4 months for multiple lead extractions. Extraction by direct manual traction was feasible in 13 patients by locking stylets in 6. Escalation to mechanical sheaths was required in 17 patients and to electrosurgical sheaths in 5. More aggressive methods were associated with longer implantation times and positive infection status. No deaths or major periprocedural complications occurred. Six minor postprocedural complications, of which three were surgically related, occurred in 5 patients. Conclusions Closed chest CS lead extraction can be safely performed with excellent results. We recommend an escalating approach from isolated manual traction over locking stylets to mechanical sheaths and, eventually, electrosurgical dissection devices. The application in mainly high-risk patients demands an interdisciplinary approach to enhance safety and limit morbidity and death.

OBJECTIVES The management of chest tubes is one of the most critical aspects in patient care in thoracic surgery, and no consensus exists regarding the ideal chest tube management strategy. METHODS Chest tube management protocols and their effects on chest tube therapy were compared at four German specialist thoracic surgery units. Altogether, 79 patients were stratified for underlying disease and type of surgery. A digital chest drainage system was applied to objectify the presence of air leakages. RESULTS In our analysis, the average length of drainage therapy was 4.9 ± 2.8 days. Different chest tube management protocols resulted in a significant degree of scatter between units (P = 0.0348). Higher arbitrary postoperative suction levels (4 kPa) resulted in earlier chest tube removal than lower suction levels (2 kPa) (4.2 ± 2.4 vs 5.4 ± 3.0 days, P = 0.06). Patient discharge following chest tube removal was delayed on average by 3.2 ± 2.9 days. This delay was not correlated with the previous duration of chest tube therapy (Spearman's ρ=-0.15, P = 0.25) in contrast to the total length of hospital stay (ρ = 0.59, P < 0.001).

Purpose. The purpose of this study is to retrospectively evaluate the efficacy and safety of the Prostar XL device for percutaneous large access site closure in an unselected patient and operator collective.Materials and Methods. All patients () who had received percutaneous vascular closing with the Prostar XL device in our institution with follow-up data of at least 6 months were retrospectively included. Primary (freedom from surgical conversion) and continued (freedom from groin surgery in further course) technical success and major (deviations from expected outcome requiring surgery) and minor (other deviations from expected outcome) complications were assessed. Success and complications rates were correlated with delivery system size (Mann-Whitney Rank Sum Tests) and operator experience (paired samplest-test).Results. Rates of primary and continued technical success as well as major and minor complications were 93.6%, 89.7%, 10.3%, and 10.3% (groin based) and 90.0%, 84.0%, 16.0%, and 16.0% (patient based), respectively. No correlation of success and complications rate was found with delivery system sizes and operator experience.Conclusions. Application of the Prostar XL device for percutaneous closure of large arterial access sites is safe with a relatively high rate of technical success and low rate of major complications. Sizes of the delivery systems and the experience of the operator did not influence the results.

We report on a peritoneal dialysis patients who presented with dyspnea, poor drainage and weight gain.A chest x-ray showed a large pleural effusion on the right side. Thoracocentesis revealed a clear protein-devoid fluid with a glucose concentration greater than that of plasma. By intraperitoneal administration of toluidine blue, a pleuroperitoneal leakage was proven.The patient underwent video-assisted thoracoscopy revealing a total of four spots of pleuroperitoneal leakage on the diaphragm after intraperitoneal administration of toluidine blue. Closure was attempted with the aid of a prolene patch which was stiched onto the diaphragm inducing adhesion to the lung. After three months bridging with hemodialysis, the peritoneal dialysis was commenced again without a recurrence of the leakage.Pleuroperitoneal leakage can occur during the course of peritoneal dialysis treatment leading to hydrothorax. Video-assisted thoracoscopy and patching of the diaphragm with a prolene mesh can be used to treat these patients.

BACKGROUND Acute rejection reactions and the development of graft arterial disease are serious limitations after transplantation. Both are connected to the expression of adhesion molecules on the activated microvascular endothelium of the allograft. METHODS siRNA-mediated silencing of ESELE, ICAM-1, and VCAM-1 on human cardiac microvascular cells (HCMEC) was investigated in order to inhibit leukocyte-endothelial interactions. HCMEC were investigated for the time-dependent expression of ESELE, ICAM-1, and VCAM-1 after TNF-α stimulation and for siRNA mediated suppression using a nonviral transfecting approach. Furthermore, the effects of siRNA transfection on leukocyte binding to the endothelium were analyzed. RESULTS Transfection with siRNA induced a significant suppression of adhesion molecule expression, regardless of whether there had been a prior single or cocktail transfection of the sequences ( P

Purpose We started a phase II trial of induction chemotherapy and concurrent hyperfractionated chemoradiotherapy followed by either surgery or boost chemoradiotherapy in patients with advanced, stage III disease. The purpose is to achieve better survival in the surgery group with minimum morbidity and mortality. Patients and Methods Patients treated from 1998 to 2002 with neoadjuvant chemoradiotherapy and surgical resection for stage III NSCLC were analyzed. The treatment consisted of four cycles of induction chemotherapy with carboplatin/paclitaxel followed by chemoradiotherapy with a reduced dose of carboplatin/paclitaxel and accelerated hyperfractionated radiotherapy with 1.5 Gy twice daily up to 45 Gy. After restaging, operable patients underwent thoracotomy. Inoperable patients received chemoradiotherapy up to 63 Gy. Study end points included resectability, pathologic response, and survival. Results One hundred twenty patients were enrolled; 25% patients had stage IIIA, 73% had stage IIIB, and 2% stage IV. After treatment, 47.5% had downstaging, 29.2% had stable disease, and 23.3% had progressive disease. Thirty patients (25%) were not eligible for operation because of progressive disease, stable disease, and/or functional deterioration with one treatment-related death. The 30-day mortality was 5% in patients who underwent operation. The 5-year survival rate for 120 patients was 21.7%, and it was 43.1% in patients with complete resection. In postoperative patients with stage N0 disease, 5-year survival was 53.3%; if stage N2 or N3 disease was still present, 5-year survival was 33.3%. Conclusion Staging and treatment with chemoradiotherapy and complete resection performed in experienced centers achieve acceptable morbidity and mortality.

Objective: In the treatment of advanced stages of lung cancer, increasingly more multimodality approaches applying radiotherapy and/or chemotherapy in a neo-adjuvant setting are being introduced. The impact of induction therapy, especially radiotherapy, on bronchial tissue viabilityhasnotbeeninvestigatedsofar.Methods:In2008,wedeterminedthetissueviabilityofbronchialsegmentsobtainedduringsurgeryin45 consecutivepatients, includingpatientsafter neo-adjuvantradiochemotherapy (RCTX).Bronchialtissue viabilitywas analysed byhistology, life— dead assay and cell proliferation in tissue-specific culture media. Biomedical findings were compared with the clinical course of the patients. Results: Tissue samples of 44 patients were included into this study. Fourteen patients (32%) had undergone neo-adjuvant RCTX. Histology and life—dead assay of the bronchial segments did not show significant differences. While patient age, sex, tumour entity and site of resection had no influence on cell proliferation in vitro, previous RCTX resulted in a 46% decrease of bronchial tissue viability (P = 0.01). However, this effect was not reflected by the clinical course of the operated patients. Conclusions: Neo-adjuvant RCTX reduces bronchial tissue viability substantially. However, this impairment does not necessarily translate into an increased rate of postoperative bronchial insufficiencies. Standard histological work-up is not sensitive enough to characterise changes in bronchial tissue viability following RCTX. # 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Background. The lack of transplant vascularization forecloses the generation and clinical implementation of bioartificial tissues. We developed techniques to generate a bioartificial human tissue with all innate vascularization. The tissue was implanted clinically as proof of concept to evaluate vascular network thrombogenicity and tissue viability after transplantation. Methods. A porcine small bowl segment was decellularized in a two-step procedure, preserving its vascular structures. The extracellular matrix was characterized quantitatively for DNA residues and protein composition. The vascular remainings were reseeded with human endothelial cells in a dynamic tissue culture. The engineered tissue was characterized by (1) histology, (2) immune-histology, (3) life-dead assay, and (4) metabolic activity. To evaluate the tissue capabilities, it was implanted clinically and recovered after 1 week. Results. Tissue preparation with sodium desoxycholate monohydrate solution resulted in an incomplete decellularization. Cell residues were removed by additional tissue incubation with DNAse. The human endothelial cells formed a viable endothelium inside the primarily porcine extracellular matrix, expressing CD31, Flk-1, and vascular endothelium-cadherin. The metabolic activity of the bioartificial tissue increased continuously over time ill vitro. Clinical tissue transplantation confirmed vessel patency and tissue viability for 1 week. Conclusions. The feasibility to bioengineer a human tissue with all innate vascularization has been shown in vitro and the clinical setting. These results may open the door for the clinical application of various sophisticated bioartificial tissue substitutes and organ replacements.