Synthetic Fibrin-Derived Bß15-42 Peptide Delays Thrombus Resolution in a Mouse Model.

[Figure: see text].

Surgical Strategy and Clinical Outcome in Patients with Bronchial Carcinoids.

Carcinoids are malignant neuroendocrine neoplasms showing good long-term survival after oncologic therapy. The study evaluated the influence of operative strategies and individual decision-making on the outcome and long-term survival in 222 patients with bronchial carcinoids. The patients underwent preoperative pulmonary function tests and bronchoscopy to facilitate surgical decision-making. A hundred and twelve tumors were detected endoscopically, including 32 in the main and lobar bronchi. We performed 5 isolated bronchus resections, 4 segmentectomies, 15 wedge resections, 10 pneumonectomies, 19 sleeve resections, 26 bilobectomies, 138 lobectomies, and 2 chest wall resections. Three patients were technically inoperable. Systematic mediastinal lymphadenectomy was routinely performed although most patients' computer tomography scans showed N0. A hundred and sixty-two patients had typical (155 N0, 7 N+) and 60 patients had atypical carcinoids (39 N0, 21 N+). There was no intraoperative mortality. The hospital mortality was below 2%. Overall, 1-, 5-, and 10-year survival rates were 99%, 94%, and 89%, respectively, in typical carcinoids. Atypical carcinoids show similar 1- and 5-year survival rates, but the 10-year survival rate was below 70%, decreasing in higher N-stages. The N-stage was the most important survival factor. In conclusion, bronchial carcinoids should be surgically treated the way lung cancer is. Anatomic resection and systematic lymphadenectomy are the treatments of choice. The availability of bronchoplastic techniques and preoperative assessment is essential for individual decision-making, focusing predominantly on postoperative quality of life.

Clinical Outcome in Patients with Nosocomial COVID-19 Infection After Thoracic Surgery.

In the present study, we retrospectively evaluated outcomes in 8 patients (mean age 67 ± 7, range 55-77 years; male/female 7/1) who acquired nosocomial COVID-19 infection postoperatively out of the 39 adults who underwent elective thoracic surgery in November 2020. All patients were tested negative for COVID-19 on admission. The mortality rate in the eight patients was 25%. The surviving six patients were discharged in a good clinical condition. Fatal outcomes were due to the development of severe and unrelenting acute respiratory distress syndrome (ARDS) and were associated with preoperatively reduced serum albumin (<3 g/dL), an open surgical approach, oxygen saturation <90% at the time of COVID-19 diagnosis, and the real-time PCR cycle threshold (Ct) value <20. A high mortality rate indicates a need for systematic and frequent COVID-19 screening in patients scheduled for elective thoracic surgery and the use of minimally invasive procedures whenever feasible.

Outcome of Repeat Pulmonary Metastasectomy.

Pulmonary metastasectomy is a well-established contribution to the cure of oligometastatic cancers, but its exact effectiveness is poorly understood. Here we report the outcomes of repeat pulmonary metastasectomy from a multicenter trial. This retrospective study included patients who underwent re-do metastasectomies between January 2010 and December 2014. The exclusion criterion was metastasectomy without curative intent. We reviewed medical files of 621 consecutive patients who underwent initial pulmonary metastasectomy. Of those, 64 patients underwent repeat metastasectomies, and these patients were included in the analysis. All the 64 patients underwent a second metastasectomy, later 35 of them underwent a third metastasectomy, 12 underwent a fourth metastasectomy, and 6 underwent a fifth metastasectomy. The total number of re-do metastasectomies was 181. The median overall survival among the patients undergoing re-do metastasectomy was 66.0 ± 3.8 months. Three and 5-year survival rates were 82.3% and 63.3%, respectively. The 5-year survival rates were 63.3% after the first, 50.9% after the second, 74.4% after the third, 83.3% after the fourth, and 60.0% after the fifth metastasectomy. We conclude that at the current stage of knowledge, there is an indication for repeat re-do metastasectomy with curative intent.

Interruption of vascular endothelial growth factor receptor 2 signaling induces a proliferative pulmonary vasculopathy and pulmonary hypertension.

Pulmonary arterial hypertension is a severe and progressive disease characterized by a pulmonary vascular remodeling process with expansion of collateral endothelial cells and total vessel occlusion. Endothelial cells are believed to be at the forefront of the disease process. Vascular endothelial growth factor (VEGF) and its tyrosine kinase receptor, VEGF receptor-2 (VEGFR-2), play a central role in angiogenesis, endothelial cell protection, but also in the destabilization of endothelial barrier function. Therefore, we investigated the consequences of altered VEGF signaling in an experimental model, and looked for translational correlates of this observation in patients. We performed an endothelial cell-specific conditional deletion of the kinase insert domain protein receptor (kdr) gene, coding for VEGFR-2, in C57/BL6 mice (Kdr∆end) and held them in an environmental chamber with 10% FiO2 or under normoxia for 6 weeks. Kdr knockout led to a mild PH phenotype under normoxia that worsened under hypoxia. Kdr∆end mice exhibited a significant increase in pulmonary arterial wall thickness, muscularization, and VEGFR-3+ endothelial cells obliterating the pulmonary artery vessel lumen. We observed the same proliferative vasculopathy in our rodent model as seen in patients receiving anti-angiogenic therapy. Serum VEGF-a levels were elevated both in the experimental model and in humans receiving bevacizumab. Interrupted VEGF signaling leads to a pulmonary proliferative arteriopathy in rodents after direct ablative gene manipulation of Kdr. Histologically, similar vascular lesions can be observed in patients receiving anti-VEGF treatment. Our findings illustrate the importance of VEGF signaling for maintenance of pulmonary vascular patency.

Physiologically based pharmacokinetic evaluation of cefuroxime in perioperative antibiotic prophylaxis.

AIMS: Adequate plasma concentrations of antibiotics during surgery are essential for the prevention of surgical site infections. We examined the pharmacokinetics of 1.5 g cefuroxime administered during induction of anaesthesia with follow-up doses every 2.5 hours until the end of surgery. We built a physiologically based pharmacokinetic model with the aim to ensure adequate antibiotic plasma concentrations in a heterogeneous population. METHODS: A physiologically based pharmacokinetic model (PK-Sim® /MoBi® ) was developed to investigate unbound plasma concentrations of cefuroxime. Blood samples from 25 thoracic surgical patients were analysed with high-performance liquid chromatography. To evaluate optimized dosing regimens, physiologically based pharmacokinetic model simulations were conducted. RESULTS: Dosing simulations revealed that a standard dosing regimen of 1.5 g every 2.5 hours reached the pharmacokinetic/pharmacodynamic target for Staphylococcus aureus. However, for Escherichia coli, >50% of the study participants did not reach predefined targets. Effectiveness of cefuroxime against E. coli can be improved by administering a 1.5 g bolus immediately followed by a continuous infusion of 3 g cefuroxime over 3 hours. CONCLUSION: The use of cefuroxime for perioperative antibiotic prophylaxis to prevent staphylococcal surgical site infections appears to be effective with standard dosing of 1.5 g preoperatively and follow-up doses every 2.5 hours. In contrast, if E. coli is relevant in surgeries, this dosing regimen appears insufficient. With our derived dose recommendations, we provide a solution for this issue.

Use of a Powered Stapling System for Minimally Invasive Lung Volume Reduction Surgery: Results of a Prospective Double-Blind Single-Center Randomized Trial.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS)-lung volume reduction surgery (LVRS) represents an important treatment option for patients with advanced lung emphysema. For VATS lung resection, endoscopic staplers are routinely used. Recently, a new generation of electronically powered stapling systems was developed. In this study, the iDrive powered stapling system (Covidien, Germany) was first tested during VATS-LVRS and compared with a non-electronic conventional device. METHODS: Forty patients with advanced emphysema were enrolled in a prospective randomized trial. All patients underwent bilateral VATS-LVRS. Patients were randomized for iDrive use on the right lung (n = 20) or left lung resection (n = 20). A conventional endoscopic stapler (EndoGIA, Covidien) was used for contralateral resection in same patients. Therefore, 40 resections were performed with the iDrive and 40 with the EndoGIA. The duration of surgery, air leakage after extubation, and on postoperative day 1 (POD1), as well as length of chest tube therapy, were documented. RESULTS: The application of the new system was uneventful. Mean duration of surgery was 52 ± 2.5 minute in the iDrive group compared with 54 ± 3.8 minute in the EndoGIA-group (p = 0.5). After extubation, the mean air leakage in the iDrive-group did not differ significantly from that in the EndoGIA-group (p = 0.6). This was also observed on POD1 (p = 0.7). Moreover, length of drainage therapy also did not show significant differences between both groups (p = 0.6). CONCLUSION: The iDrive powered stapling system offers one-handed, push-button operation, which eliminates the manual firing force and possibly enables more precise resection. In the current study, the novel system led to comparable results with the conventional mechanical stapler without any disadvantages in patients undergoing bilateral VATS-LVRS.

[Extracorporeal Lung Support in Thoracic Surgery: Basics and Pathophysiology]. / ECMO in der Thoraxchirurgie: Grundlagen und Pathophysiologie.

Extracorporeal lung support (ECLS) is of increasing importance in general thoracic surgery. Different modes of ECLS may be applied in several situations throughout the perioperative phase and are adapted to the individual patient's needs and the planned surgical procedures. ECLS is not a static procedure and should be always evaluated according to the present condition of the patient. Therefore, it is essential to understand the pathophysiology of the disease and the different ECLS modes, as well as the different cannulation options, in order to be able to use the different escalation and de-escalation techniques in accordance with the clinical situation.

Perioperative single-site veno-venous extracorporeal CO2 removal for minimally invasive giant bulla resection.

Giant pulmonary bullae are rare and surgical management of patients with severe emphysema and advanced chronic obstructive lung disease (COPD) presenting with giant bullae can be very challenging. Previously, perioperative, two-site, high-flow, veno-venous extracorporeal membrane oxygenation (ECMO) was successfully utilized during giant bulla resection. Here we report the perioperative application of single-site, low-flow extracorporeal CO2 removal (ECCO2R) for minimally invasive thoracoscopic giant bulla resection. This approach of low-flow, veno-venous ECCO2R, which is less invasive than conventional ECLS approaches, has enabled the safe performance of surgery and facilitated protective intraoperative single-lung ventilation while avoiding possible complications of aggressive mechanical ventilation.

[Management of Thoracic Trauma]. / Thoraxtrauma: Diagnostik und Therapie.

Patients with a thoracic trauma are commonly treated by large bore chest tube thoracostomy and appropriate analgesia. The initial treatment is determined by the assessment of the emergency doctor and/or trauma surgeon. Severe intrathoracic lesions in polytrauma patients are rare. However, such injuries may be acutely life-threating. After primary stabilisation of the patients, imaging studies should be performed to assess the extent of the injuries and determine the treatment of choice. Assessment of such injuries should always be performed in a multidisciplinary team of anaesthesiologists, general surgeons, trauma surgeons and thoracic surgeons. For this reason, patients with thoracic traumas should always be treated in specialised centers. This approach reduces overall mortality and shortens the length of hospital stay.

Thoracic Wall Reconstruction with Acellular Porcine Dermal Collagen Matrix.

BACKGROUND: Major thoracic wall resections require the implantation of foreign materials for reconstruction and stabilization. Recently, biological collagen matrixes have emerged as an alternative to the routinely used synthetic materials. MATERIALS AND METHODS: Retrospectively, we analyzed our initial experience of chest wall reconstruction on large defects using a cross-linked porcine dermal acellular collagen matrix mesh with a thickness of 1.5 mm. RESULTS: Six sarcoma patients with a mean age of 46 (22-66) years underwent chest wall resections. Complete thoracic wall defects (mean area 149 cm2) ranged from 8 × 10 to 15 × 20 cm in size. In the majority of cases, only mobilized subcutaneous tissue and skin were used for soft-tissue coverage of the implanted porcine collagen matrix patches. Implantation and postoperative courses were uneventful in all patients. No local infections or wound healing problems occurred. The collagen material resulted in durable and good to excellent chest wall stability in clinical follow-ups, and on computed tomography scans spanning over 3.5 years. Histological examination showed integration, neovascularization, and long-term persistence of the collagen matrix on late reoperation of one patient. CONCLUSION: Acellular porcine dermal collagen matrix is a feasible and reliable biological patch material for reconstruction of the thoracic wall. Excellent wound healing and long-term stability are achieved even in large defects or complete sternal replacements.

Platelet endothelial cell adhesion molecule 1 deficiency misguides venous thrombus resolution.

Platelet endothelial cell adhesion molecule 1 (PECAM-1) is involved in leukocyte migration and angiogenesis, which are key components of venous thrombus resolution. This study investigated the effect of PECAM-1 deficiency on thrombus resolution in FVB/n mice and the extent to which levels of soluble PECAM-1 (sPECAM-1) correlate with delayed thrombus resolution in humans after acute symptomatic deep vein thrombosis (DVT). In a mouse stagnant flow venous thrombosis model Pecam-1(-/-) thrombi were larger, persisted for longer periods of time, and displayed attenuated macrophage invasion and decreased vessel formation in the presence of increased fibrosis. In humans, higher levels of truncated plasma sPECAM-1 possibly cleaved from cell surfaces, were found in patients with delayed thrombus resolution (assessed via duplex-based thrombus scoring) relative to those whose thrombi resolved (median, 25th/75th percentile): 92.5 (87.7/103.4) ng/mL vs 71.5 (51.1/81.0) ng/mL; P < .001. Furthermore, unresolved human deep vein thrombus specimens stained positively with antibodies specific for the extracellular, but not the cytoplasmic domain of PECAM-1, consistent with accumulation of cleaved PECAM-1. Our data suggest a regulatory role of PECAM-1 in venous thrombus resolution and suggest a predictive value of sPECAM-1 for postthrombotic syndrome (PTS) after acute DVT.

Defective angiogenesis delays thrombus resolution: a potential pathogenetic mechanism underlying chronic thromboembolic pulmonary hypertension.

OBJECTIVE: Restoration of patency is a natural target of vascular remodeling after venous thrombosis that involves vascular endothelial cells and smooth muscle cells, as well as leukocytes. Acute pulmonary emboli usually resolve <6 months. However, in some instances, thrombi transform into fibrous vascular obstructions, resulting in occlusion of the deep veins, or in chronic thromboembolic pulmonary hypertension (CTEPH). We proposed that dysregulated thrombus angiogenesis may contribute to thrombus persistence. APPROACH AND RESULTS: Mice with an endothelial cell-specific conditional deletion of vascular endothelial growth factor receptor 2/kinase insert domain protein receptor were used in a model of stagnant flow venous thrombosis closely resembling human deep vein thrombosis. Biochemical and functional analyses were performed on pulmonary endarterectomy specimens from patients with CTEPH, a human model of nonresolving venous thromboembolism. Endothelial cell-specific deletion of kinase insert domain protein receptor and subsequent ablation of thrombus vascularization delayed thrombus resolution. In accordance with these findings, organized human CTEPH thrombi were largely devoid of vascular structures. Several vessel-specific genes, such as kinase insert domain protein receptor, vascular endothelial cadherin, and podoplanin, were expressed at lower levels in white CTEPH thrombi than in organizing deep vein thrombi and organizing thrombi from aortic aneurysms. In addition, red CTEPH thrombi attenuated the angiogenic response induced by vascular endothelial growth factor. CONCLUSIONS: In the present work, we propose a mechanism of thrombus nonresolution demonstrating that endothelial cell-specific deletion of kinase insert domain protein receptor abates thrombus vessel formation, misguiding thrombus resolution. Medical conditions associated with the development of CTEPH may be compromising early thrombus angiogenesis.

Prognostic value of culprit site neutrophils in acute coronary syndrome.

BACKGROUND: Recent data suggest that acute coronary syndromes (ACS) and acute myocardial infarction (AMI) are characterized by an inflammatory subset of thrombosis. We have previously described the accumulation of neutrophils at the coronary culprit lesion site. In this work, we assessed the prognostic value of culprit site (CS) neutrophil accumulation on long-term mortality in patients with AMI. MATERIALS AND METHODS: In this prospective study, 417 AMI patients were enrolled after thrombectomy during primary percutaneous coronary intervention. The optimal cut-off for CS neutrophil accumulation for predicting 4-year all-cause mortality was calculated using time-dependent receiver operator characteristic curve analyses. RESULTS: The median follow-up time was 39 months interquartile range (IQR 21·4-54·6 months) corresponding to 1217 patient years of follow-up. The cut-off for CS neutrophil accumulation (difference between culprit neutrophil counts and systemic neutrophil counts) was 0·25 Giga/l. CS neutrophil accumulation occurred in 195 patients (47%) and was independently associated with mortality (hazard ratio 1·88 (95%CI 1·02-3·41, P = 0·043)). In patients with CS neutrophil accumulation, 1-year mortality (10·8% vs. 7·2%) and 4-year mortality (19·8% vs. 10·4%) were markedly increased compared with patients without local neutrophil accumulation. Concordance index for CS neutrophil accumulation and mortality was 0·64 (95% CI 0·51-0·77; P = 0·035). Patients with CS neutrophil accumulation had significantly more often nonobstructive lesions compared with patients without neutrophil accumulation (32·6% vs. 22·4%; P = 0·024). CONCLUSIONS: Neutrophil accumulation at the coronary culprit lesion site is a strong and independent predictor of mortality in patients with ACS/AMI.

Survival results after implantation of intrapericardial third-generation centrifugal assist device: an INTERMACS-matched comparison analysis.

Reports on third-generation centrifugal intrapericardial pumps (HeartWare International, Inc., Framingham, MA, USA) have shown better survival results than the previous-generation devices. However, outcomes depending on the preoperative level of stability can substantially differ, resulting in a limited analysis of potentialities and drawbacks of a given device. In the present study we sought to compare in our single-center experience the survival results of this third-generation device with previous left ventricular systems taking into account the different preoperative Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) levels. Between February 1993 and March 2012, 287 patients underwent assist device implantation in our university hospital (INTERMACS Level 1-2 = 158 patients; INTERMACS Level 3-4-5 = 129 patients). Assist devices implanted were: Group A (HVAD HeartWare, n = 52), group B (previous continuous-flow ventricular assist device [VAD], InCor [Berlin Heart, Berlin, Germany], n = 37; VentrAssist [VentraCor, Inc., Chatswood, NSW, Australia], n = 7; DeBakey [MicroMed Cardiovascular, Inc., Houston, TX, USA], n = 32), and group C (pulsatile systems, n = 159). After cumulative support duration of 54 436 days and a mean follow-up of 6.21 ± 7.46 months (range 0-45.21 months), log-rank analysis revealed a survival for group A of 82.0%, 70.4%, and 70.4%; for group B of 84.0%, 48.2%, 33.7%; and for group C of 71.6%, 46.1%, 33.8%, at 1, 12, and 24 months respectively, with a significantly (P = 0.013) better outcome for group A. When stratifying the survival on the basis of INTERMACS level, no significant survival improvement was observed among all patients who underwent VAD implantation in INTERMACS 1-2 (P = 0.47). However, among patients who underwent elective VAD implantation (INTERMACS 3-4-5), group A had a significantly better outcome (P = 0.005) compared with the other INTERMACS-matched groups (B,C) with a survival rate of 88.8% in group A versus 34.2% in group B and 45.6% in group C at 24 months, respectively. Elective HVAD system implantation shows improved survival benefit over the other INTERMACS-matched devices. Moreover, preoperative unstable hemodynamics resulted in a poor prognosis independently from the pump generation.

Pectus excavatum and cardiac surgery: simultaneous correction advocated.

BACKGROUND: Severe pectus excavatum may be present in combination with cardiac conditions requiring open-heart surgery. The best strategy for this situation has been debated controversially. PATIENTS AND METHODS: In a retrospective study, we analyzed all our patients undergoing concurrent pectus excavatum correction and open-heart surgery. RESULTS: Ten patients aged 9 to 70 years underwent a simultaneous combined surgical procedure between 2001 and 2013. Indications for cardiac surgery were various forms of congenital and acquired heart disease including coronary artery disease with internal thoracic artery grafts and ascending aortic aneurysms. A modified Ravitch procedure was performed for pectus excavatum correction (mean Haller-Index 5.0). Mean operating time was 364 (210-495) minutes and mean duration of cardiopulmonary bypass was 125 (54-222) minutes. All procedures were completed successfully. Postoperatively minor complications were observed in three patients. In-hospital and 30-day mortalities were nil. Good cosmetic and functional results were achieved in all patients. CONCLUSIONS: Our data demonstrate that simultaneous pectus excavatum correction and cardiac surgery is effective and reliable. A combined approach is advocated if candidates for cardiac surgery present with significant pectus excavatum deformity.

An unusual case of a tension pneumothorax.

A total intra-thoracic stomach describes the case of a complete herniation of the stomach into the thoracic cavity. Symptoms may vary from mild to an acute life-threatening situation in case of perforation or bleeding, requiring emergency surgery. Here we describe the case of a gastric perforation leading to a tension pneumothorax and concomitant pleural empyema due to a giant hiatal recurrence after previous surgery. Multidisciplinary management involving thoracic surgeons helped in achieving the best clinical outcome for the patient.

Role of Pre-Operative Brain Imaging in Patients with NSCLC Stage I: A Retrospective, Multicenter Analysis.

Background: Lung cancer is the worldwide leading oncological cause of death in both genders combined and accounts for around 40-50% of brain metastases in general. In early-stage lung cancer, the incidence of brain metastases is around 3%. Since the early detection of asymptomatic cerebral metastases is of prognostic value, the aim of this study was to analyze the incidence of brain metastases in early-stage lung cancer and identify possible risk factors. Methods: We conducted a retrospective multicentric analysis of patients with Stage I (based on T and N stage only) Non-Small Cell Lung Cancer (NSCLC) who had received preoperative cerebral imaging in the form of contrast-enhanced CT or MRI. Patients with a history of NSCLC, synchronous malignancy, or neurological symptoms were excluded from the study. Analyzed variables were gender, age, tumor histology, cerebral imaging findings, smoking history, and tumor size. Results were expressed as mean with standard deviation or median with range. Results: In total, 577 patients were included in our study. Eight (1.4%) patients were found to have brain metastases in preoperative brain imaging. Tumor histology was adenocarcinoma in all eight cases. Patients were treated with radiotherapy (five), surgical resection (two), or both (one) prior to thoracic surgical treatment. Other than tumor histology, no statistically significant characteristics were found to be predictive of brain metastases. Conclusion: Given the low incidence of brain metastases in patients with clinical Stage I NSCLC, brain imaging in this cohort could be avoided.

Lung volume reduction surgery: from National Emphysema Treatment Trial to non-intubated awake video-assisted thoracoscopic surgery.

Chronic obstructive pulmonary disease (COPD) is a major public health problem. Loss of elastic recoil, hyperinflation and obstruction of the expiratory airflow lead to an increased breathing work, which results in dyspnea during minimal physical activity of the patients. Reduction of the lung volume in these patients leads to improvement of dyspnea, physical activity and quality of life in these patients. Beside endoscopic lung volume reduction (ELVR), lung volume reduction surgery (LVRS) represents an important and valuable treatment option for patients with advanced lung emphysema. Since the National Emphysema Treatment Trial (NETT), thoracic surgery experienced a remarkable evolution of the surgical techniques enabling safe surgery and quick recovery in this critically ill patient cohort. A paradigm shift from open surgical approaches to most minimally invasive techniques accompanied by improvement of anesthesiologic management of these patients was evident. Moreover, indications for LVRS, which were originally described in the NETT, were extended to apply for further groups of patients with advanced lung emphysema, enabling significant clinical improvement in well-selected patients with a low perioperative morbidity and mortality. The current review will give an overview of the historical approaches for LVRS, highlight the indications for LVRS and discuss the development of the surgical approaches.