Correction: Macrophage-expressed IFN-ß Contributes to Apoptotic Alveolar Epithelial Cell Injury in Severe Influenza Virus Pneumonia.

[This corrects the article DOI: 10.1371/journal.ppat.1003188.].

Thoracotomy versus video-assisted thoracoscopic surgery (VATS) in stage III empyema-an analysis of 217 consecutive patients.

BACKGROUND: Pleural empyema is an infectious disease of the chest cavity, with a high morbidity and mortality. According to the American Thoracic Society, pleural empyema gets graduated into three stages, with surgery being indicated in intermediate stage II and chronic stage III. Evidence for the feasibility of a minimally-invasive video-assisted thoracoscopic approach in stage III empyema for pulmonary decortication is still little. METHODS: Retrospective single-center analysis of patients conducted to surgery for chronic stage III pleural empyema from 05/2002 to 04/2014 either by video-assisted thoracoscopic surgery (VATS, n = 110) or conventional open surgery by thoracotomy (n = 107). Multiple regression analysis and propensity score matching was used to evaluate the influence of operation technique (thoracotomy versus VATS) on the length of post-operative hospitalization. RESULTS: Operation time was longer in the thoracotomy-group (p = 0.0207). Conversion rate from VATS to open surgery by thoracotomy was 4.5%. Post-operative complication- (61 patients in thoracotomy- and 55 patients in VATS-group), recurrence- (3 patients in thoracotomy- and 5 in VATS-group) and mortality-rates (6.5% in thoracotomy- and 9.5% in VATS-group) did not differ between both groups; the length of (post-operative) stay at intensive care unit was longer in the VATS-group (p = 0.0023). Duration of chest tube drainage and prolonged air leak rate were similar among both groups, leading to a similar overall and post-operative length of hospital stay in both groups. Adjusted to clinically and statistically relevant confounders, multiple regression analysis showed an influence of the surgical technique on length of post-operative stay after pair matching of the patients (n = 84 in each group) by propensity score (B = - 0.179 for thoracotomy = 0 and VATS = 1, p = 0.032) leading to a reduction of 0.836 days after a VATS-approach compared to thoracotomy. CONCLUSIONS: VATS in late stage (III) pleural empyema is feasible and safe. The decrease in post-operative hospitalization demonstrated by adjusted multiple regression analysis may indicate the minimally-invasive approach being safe, more tolerable for patients, and more effective.

Stage-directed therapy of pleural empyema.

PURPOSE: Intensivists and surgeons are often confronted with critically ill patients suffering from pleural empyema. Due to it' s multifactorial pathogenesis and etiology, medicals should be sensitized to recognize the different stages of the disease. Besides a whole bundle of different established classification systems, the progress of pleural effusions can be subdivided into the early exudative, the intermediate fibropurulent and the late organized phase according to the classification of the American Thoracic Society. RESULTS: Rapid diagnosis of pleura empyema is essential for patients' survival. Due to the importance of stage-adapted therapeutic decisions, different classification systems were established. Depending on the stage of pleural empyema, both antimicrobial and interventional approaches are indicated. For organized empyema, minimally invasive and open thoracic surgery are gold standard. Surgery is based on the three therapeutic columns: removal of pleural fluid, debridement and decortication. In general, therapy must be intended stage-directed following multidisciplinary concepts including surgeons, intensivists, anesthesiologists, physiotherapists and antibiotic stewards. Despite an established therapeutic algorithm is presented in this review, there is still a lack of randomized, prospective studies to evaluate potential benefits of minimally invasive (versus open) surgery for end-stage empyema or of catheter-directed intrathoracic fibrinolysis (versus minimally invasive surgery) for intermediate-stage pleural empyema. Any delay in adequate therapy results in an increased morbidity and mortality. CONCLUSION: The aim of this article is to review current treatment standards for different phases of adult thoracic empyema from an interdisciplinary point of view.

Management of a solitary pulmonary arteriovenous malformation by video-assisted thoracoscopic surgery and anatomic lingula resection: video and review.

BACKGROUND: Pulmonary arteriovenous malformations are abnormal communications between the pulmonary arterial and venous vasculature leading to a right-to-left blood shunt. Based on possible complications, including hypoxemia, hemorrhage, infection and paradoxical embolism, deactivation of the malformation from the circulation is the treatment option of choice, either by interventional embolization or by surgery. Embolization is less invasive and has widely replaced surgery, but bears the risk of revascularization, recanalization and downstream migration of the device with paradoxical embolism. METHODS: We report on the case of a 76-year-old male patient suffering from a complex, plexiform pulmonary arteriovenous malformation in the lingula, which was treated by video-assisted thoracoscopic surgery and anatomic lingula resection. Patient's medical history, clinical examination and imaging studies did not reveal any evidence of hereditary hemorrhagic telangiectasia. RESULTS: Left-sided anterior three-port video-assisted thoracoscopic surgery (VATS) approach was used. Instead of only wedge resecting the very peripherally located pulmonary arteriovenous malformation, the lingular vessels were controlled centrally and an anatomic lingula resection was performed in order to prevent a more central re-malformation. To prevent rupture of the aneurysm sac through pressure overload, the feeding arteries were controlled before the draining vein. Duration of the total procedure was 151 min, the single chest tube was removed on the postoperative day 3, and the patient was discharged on the postoperative day 6. CONCLUSION: Although interventional embolism of the feeding artery of a pulmonary arteriovenous malformation is the current therapeutic gold standard, minimally invasive anatomic lung resection by video-assisted thoracoscopic surgery can be considered, especially for the treatment of solitary large arteriovenous malformations. By anatomic lung resection, the risk of recanalization, collateralization and peri-interventional paradoxical embolism may be reduced.

A standardized technique of systematic mediastinal lymph node dissection by video-assisted thoracoscopic surgery (VATS) leads to a high rate of nodal upstaging in early-stage non-small cell lung cancer.

BACKGROUND: A substantial part of the oncologic surgical procedure in non-small cell lung cancer (NSCLC) is systematic lymph node dissection (sLND). However, controversies still exist regarding the quality of minimally invasive (video-assisted thoracoscopic surgery, VATS) sLND in oncologic resections. The rate of stage migration from clinical to pathological N-status has been discussed as one parameter for the quality of sLND. METHODS: Between March 2011 and May 2014, seventy-seven patients (62 male, 15 female) were scheduled for anatomical lung resection and sLND by VATS for clinical stage I (UICC 7th edition) NSCLC. Preoperative staging was performed by [18F]-fluorodesoxyglucose positron emission tomography with computed tomography (FDG-PET/CT). Patient data were retrospectively analyzed with regard to divergence in clinical and pathological N-factor. FDG-PET/CTs of patients with lymph node (LN) upstaging after VATS resections were blindly re-evaluated by an experienced radiologist. RESULTS: In FDG-PET/CT, preoperative tumor stage was cT1N0M0 in 41 (53.2%) and cT2aN0M0 in 28 (36.4%) patients. In six (7.8%) patients the primary tumor was not suspicious for malignancy, and in two (2.6%) patients the tumor was not evaluable due to prior wedge resection before FDG-PET/CT. Thirty-one (40.3%) left-sided and 46 (59.7%) right-sided pulmonary resections with sLND were performed; 19.57 ± 0.99 LNs were dissected. In 13 (16.9%) patients a nodal stage migration from preoperative clinical to postoperative pathological N-stage was observed [cN0 to pN1 in 9 (11.7%) and cN0 to pN2 in 4 (5.2%) cases]. In correlation to the clinical T-factor, the rate of N-factor upstaging for cT1 was 12.2% and for cT2a was 28.6%, respectively. In 50% of the patients with postoperative nodal staging shift, no changes were observed on re-evaluation of the preoperative FDG-PET/CT. CONCLUSION: In this series of clinical stage I NSCLC patients, the rate of nodal stage migration after sLND by VATS is higher than previously reported. Prospective randomized controlled trials are needed to prove the oncologic quality of a sLND by VATS versus standard open approach.

Extended minimally invasive lung resections: VATS bilobectomy, bronchoplasty, and pneumonectomy.

PURPOSE: The aim of the present study was to analyze feasibility, morbidity, mortality, and oncologic outcome of extended video-assisted thoracoscopic surgery (VATS) anatomic lung resections in a single-center experience. Extended resections include bilobectomies, bronchoplasties, and pneumonectomies. METHODS: The present study is a retrospective analysis of a prospectively maintained institutional database. Between 2009 and 2014, 390 patients were scheduled for anatomical VATS resections. VATS resection was completed in 370 patients giving an overall conversion rate of 5.1 %. Extended VATS resections were performed in 29 patients (7.8 %): bilobectomy in 8, bronchoplastic resection in 15 (2 bronchial sleeve resections, 11 wedge bronchoplasties, 2 simple bronchoplasties), and pneumonectomy in 6. RESULTS: Median operative time was 217 min (117-390 min). Median chest tube duration was 4 days (range, 2-50 days). Median length of hospital stay was 9 days (6-63 days). There was no in-hospital mortality. Major complications with need for reinterventions occurred in three patients (10.3 %): one air leakage from bronchial stump after pneumonectomy, one hematothorax after completion pneumonectomy, and one chylothorax. All complications were treated with VATS procedures. Minor complications included two persistent air leaks that were treated with an additional chest drain and resolved, one urinary tract infection, one atelectasis with need for bronchoscopy, and one pleural fluid collection with the need for drainage. After a median follow-up of 26 months, no local tumor recurrence occurred. Two patients had a second lung primary cancer and four patients with advanced tumor stages had distant recurrent disease. CONCLUSIONS: With growing experience, extended VATS resections are feasible in selected cases with low perioperative morbidity and mortality.

Anatomic lung resections for benign pulmonary diseases by video-assisted thoracoscopic surgery (VATS).

PURPOSE: Based on increasing evidence of its benefits regarding perioperative and oncologic outcome, video-assisted thoracoscopic surgery (VATS) has gained increasing acceptance in the surgical treatment of early stage non-small cell lung cancer (NSCLC). However, the evidence for a VATS approach in anatomic lung resection for benign pulmonary diseases is still limited. METHODS: Between March 2011 and May 2014, data from 33 and 63 patients who received VATS anatomic lung resection for benign diseases (VATS-B) and early stage NSCLC (VATS-N), respectively, were analyzed retrospectively. For subgroup analyses, VATS-B was subdivided by operation time and underlying diseases. Subgroups were compared to VATS-N. RESULTS: Three patients from VATS-B and four from VATS-N experienced conversion to open surgery. Causes of conversion in VATS-B were intraoperative complications, whereas conversions in VATS-N were elective for oncological concerns (p < 0.05). Operation time and duration of postoperative mechanical ventilation were longer by tendency; postoperative stay on intensive care unit and chest tube duration were significantly longer in VATS-B. Subgroup analyses showed a longer operation time as a predictor for worse perioperative outcome regarding postoperative mechanical ventilation, postoperative stay on intensive care unit, chest tube duration, and length of hospital stay. Patients with longer operation time suffered from more postoperative complications. Differences in perioperative outcome data were not significantly dependent on the underlying benign diseases compared to VATS-N. CONCLUSIONS: VATS is feasible and safe in anatomic lung resection for benign pulmonary diseases. Not the underlying disease, but a longer operation time is a factor for worse postoperative outcome.

Video-assisted thoracoscopic anatomic lung resections in Germany-a nationwide survey.

PURPOSE: Video-assisted thoracoscopic surgery (VATS) is an accepted alternative to thoracotomy for anatomic lung resection (AR) and literature suggests benefits over the conventional open approach. However, it's routine clinical application is still low and varies within different countries. METHODS: Nationwide survey among thoracic surgical units in Germany, evaluating the departmental structure, volume of the VATS program, experience with VATS-AR (lobectomies and other-than-lobectomies-anatomic-resections), surgical technique and learning curve data. RESULTS: Response rate among the 269 surgical units practicing thoracic surgery in Germany was 84.4 % (n = 227). One hundred twenty-two (53.7 %) units do have experience with any type of VATS-AR. The majority of units started the VATS program only within the last 5 years and 17.2 % (n = 21) of the units have performed more than 100 procedures by now. In 2013, 78.7 % of the units performed less than 25 % of their institutional AR via a VATS approach. Indications for VATS-AR were non-small cell lung cancer in 93.4 % (up to UICC-stage IA, IB, IIA, IIB, IIIA in 7 %, 22.8 %, 33.3 %, 17.5 %, 7 %, respectively), benign diseases in 57.4 %, and pulmonary metastases in 50.8 %. 43.4 % of the departments had experience with extended VATS-AR and 28.7 % performed VATS-AR after induction-therapy. CONCLUSIONS: Every second thoracic surgical unit in Germany does have experience in VATS-AR though only about 20 % of them perform it routinely and also in extended procedures.

Macrophage-expressed IFN-ß contributes to apoptotic alveolar epithelial cell injury in severe influenza virus pneumonia.

Influenza viruses (IV) cause pneumonia in humans with progression to lung failure and fatal outcome. Dysregulated release of cytokines including type I interferons (IFNs) has been attributed a crucial role in immune-mediated pulmonary injury during severe IV infection. Using ex vivo and in vivo IV infection models, we demonstrate that alveolar macrophage (AM)-expressed IFN-ß significantly contributes to IV-induced alveolar epithelial cell (AEC) injury by autocrine induction of the pro-apoptotic factor TNF-related apoptosis-inducing ligand (TRAIL). Of note, TRAIL was highly upregulated in and released from AM of patients with pandemic H1N1 IV-induced acute lung injury. Elucidating the cell-specific underlying signalling pathways revealed that IV infection induced IFN-ß release in AM in a protein kinase R- (PKR-) and NF-κB-dependent way. Bone marrow chimeric mice lacking these signalling mediators in resident and lung-recruited AM and mice subjected to alveolar neutralization of IFN-ß and TRAIL displayed reduced alveolar epithelial cell apoptosis and attenuated lung injury during severe IV pneumonia. Together, we demonstrate that macrophage-released type I IFNs, apart from their well-known anti-viral properties, contribute to IV-induced AEC damage and lung injury by autocrine induction of the pro-apoptotic factor TRAIL. Our data suggest that therapeutic targeting of the macrophage IFN-ß-TRAIL axis might represent a promising strategy to attenuate IV-induced acute lung injury.

Total video-assisted thoracoscopic (VATS) resection of a left-sided sulcus superior tumor after induction radiochemotherapy: video and review.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) has gained increasing acceptance for surgical therapy of early stage non small cell lung cancer (NSCLC). Even for extended pulmonary resections in advanced tumor stages, increasing evidence suggests feasibility and safety of the VATS approach. However, so far very little experience has been reported on VATS management of sulcus superior tumors. METHODS: We report on a 56-year-old female patient with a left-sided anterior sulcus superior adenocarcinoma (cT3 cN1 cM0), which was completely resected by VATS after induction radiochemotherapy. RESULTS: The surgical procedure was performed completely minimally invasively via a three-incision anterior thoracoscopic approach. The total operating time was 285 min (composed of 116 min for hilar lobectomy, 103 min for sulcus superior preparation and chest wall resection, and 26 min for systematic en-bloc lymph node dissection). The single chest tube was removed on postoperative day two and the patient was discharged on postoperative day six. No intraoperative and no postoperative complications were observed. Histopathology confirmed a complete (R0) resection of an ypT2aN0M0 bronchogenic adenocarcinoma. CONCLUSION: With increasing experience even extended pulmonary resections are safe and feasible by a video-assisted thoracoscopic approach. We propose that in sulcus superior tumors without tumor invasion of vascular structures VATS can be considered.

Robotic-assisted minimally invasive vs. thoracoscopic lung lobectomy: comparison of perioperative results in a learning curve setting.

PURPOSE: Minimally invasive lung lobectomy was introduced in the late 1990s. Since that time, various different approaches have been described. At our institution, two different minimally invasive approaches, a robotic and a conventional thoracoscopic one, were performed for pulmonary lobectomies. This study compares perioperative outcome of the two different techniques in a learning curve setting. METHODS: Between 2001 and 2008, 26 patients underwent lung lobectomy with a robotic-assisted thoracoscopic surgery (RATS) technique. In 2009, the minimally invasive approach was changed to a conventional video-assisted thoracoscopic surgery (VATS) technique. Perioperative results of the first 26 VATS patients were compared to the results of the robotic group. RESULTS: There were significantly more patients with clinical stage >IB in the VATS group than in the robotic-assisted group (23.1 vs. 0 %). Otherwise, demographic data were equal between the groups. Operative time was significantly longer in the robotic group (215 vs. 183 min, p = 0.0362). Median difference between preoperative hemoglobin levels and levels on postoperative day 1 was higher in the RATS group, suggesting a higher blood loss. No difference was found in conversion rate, acute phase protein levels (C-reactive protein), chest drain duration, postoperative morbidity and mortality, and length of hospital stay. Procedural costs were higher for the robotic approach (difference, 770.55 , i.e., 44.4 %). CONCLUSIONS: Shorter operative times, a lower drop of postoperative hemoglobin levels indicating less blood loss, and lower procedural costs suggest a benefit of the VATS approach over the robotic approach for minimally invasive lung lobectomy.

Awake Uniportal VATS for the Evacuation of an Extensive, Superinfected Hemothorax in a Patient with Advanced Mediastinal SMARCA4-Deficient Tumor.

Background The so-called nonintubated or awake video-assisted thoracoscopic surgery (NIVATS) is performed on spontaneously breathing patients, which was shown to reduce postoperative complications and shorten hospital stay. Case Description Awake uniportal VATS was indicated for the evacuation of an extensive, superinfected hemothorax with symptomatic mediastinal shift in a patient with advanced mediastinal SMARCA4-deficient tumor and declined condition, who did not allow a general anesthetic procedure and was not a candidate for extensive surgery. Conclusion This short microinvasive intervention was a prerequisite to stabilize the threat to the patient's life and thus potentially enable any further tumor-specific therapy.

Rescue surgery in palliative indication as last therapeutic option for complicated advanced stage lung cancer.

OBJECTIVE: To evaluate the role of rescue surgery in complicated initially not operatively intended advanced stage lung cancer. MATERIALS AND METHODS: Retrospective analysis of 30 patients with advanced lung cancer who underwent rescue surgery for control of life-threatening, non-conservatively manageable tumor related complications like post-obstructive pneumonia, super-infected tumor necrosis or active bleeding. Study parameters included tumor stage, histology, type of resection, and patients' characteristics as well as postoperative outcomes. RESULTS: The study cohort consisted of 12 female and 18 male patients, among those 29 were diagnosed with Non-Small Cell Lung Cancer (NSCLC) and one with Small Cell Lung Cancer (SCLC). On initial tumor-diagnosis 20 patients had been classified as stage IV and 9 with stage III; 1 patient had not yet been completely staged at time of surgery for active tumor bleeding. In all patients, the indication for rescue surgery was not oncologic-therapeutic but to control non-conservatively manageable complications which either contradicted any tumor-specific systemic therapy or acutely threatened life. Types of resections included pneumonectomy, bi-lobectomy, lobectomy and segmentectomy. The mean overall survival was 13.3 (median 11.2) months, the 1-year-survival-probability of the cohort was 45,2%. The 30- and 90-day mortality was 13,3 and 30%, respectively. The reasons for early postoperative mortality were ARDS, multiorgan failure and bronchial-stump insufficiency. CONCLUSIONS: Rescue surgery for tumor- or therapy-induced life-threatening complications in patients with advanced stage lung cancer is associated with high morbidity and mortality. However, if all other treatment options have failed it nevertheless may be indicated as the last therapeutic chance and if surgery succeeds in controlling the acute event it may also set the condition for subsequent tumor-specific therapies. Future research should focus on elaborating effective criteria regarding patient selection and timing of surgery in order to restrict these high-risk-operations to only those patients, who most likely will benefit.

Initial experience with robotic lung lobectomy: report of two different approaches.

BACKGROUND: Surgical resection is the gold standard for treatment of early-stage lung tumors. Different minimally invasive approaches are currently under investigation: In addition to conventional video-assisted thoracoscopic surgery (VATS), robotic technology with the da Vinci System has emerged over the past 10 years. METHODS: In this series, 26 patients (12 women and 14 men; median age, 65 years) underwent a robotic lobectomy for early-stage lung tumors (clinical stage IA or IB) or centrally located metastases. RESULTS: The resected lobes included four left upper lobes, six left lower lobes, eight right upper lobes, and eight right lower lobes. Five intraoperative conversions to open thoracotomy were performed due to one major bleeding, two minor bleedings, one variant course of the pulmonary artery, and one extended resection. The postoperative complications included two prolonged air leaks, one colonic perforation, and one atrial fibrillation. The median hospital stay was 11 days (range, 7-53 days). One 30-day mortality (3.8%) occurred due to respiratory failure. The overall median operative time was 228 min (range, 162-375 min). For the first five patients, the posterior approach was used. Thereafter, the authors switched to an anterior approach, thus enabling an easier hilar dissection. Technical modification within this series also included the introduction of a new vessel sealing device. CONCLUSION: Robotic lobectomy was proved to be feasible and safe in our initial series in a learning curve setting. Changes in patient positioning and approach as well as technical modifications resulted in shorter operative times. A longer follow-up period and randomized controlled trials are necessary to evaluate a potential benefit over open and conventional VATS approaches.

Robotic surgery of the mediastinum.

Several different mediastinal procedures for benign and malignant diseases have been proved to be feasible and safe when performed by a robotic minimally invasive approach. This article reviews the published data on robotic mediastinal surgery, focusing on technical aspects and perioperative outcomes. These are evaluated for differences and potential benefits over open and conventional minimally invasive techniques. Is there a need for the robot in the mediastinum? Is its application justified?

Ivor Lewis esophagectomy patients are particularly vulnerable to respiratory impairment - a comparison to major lung resection.

Pulmonary complications and a poor clinical outcome are common in response to transthoracic esophagectomy, but their etiology is not well understood. Clinical observation suggests that patients undergoing pulmonary resection, a surgical intervention with similarities to the thoracic part of esophagectomy, fare much better, but this has not been investigated in detail. A retrospective single-center analysis of 181 consecutive patients after right-sided thoracotomy for either Ivor Lewis esophagectomy (n = 83) or major pulmonary resection (n = 98) was performed. An oxygenation index <300 mm Hg was used to indicate respiratory impairment. When starting surgery, respiratory impairment was seen more frequently in patients undergoing major pulmonary resection compared to esophagectomy patients (p = 0.009). On postoperative days one to ten, however, esophagectomy caused higher rates of respiratory impairment (p < 0.05) resulting in a higher cumulative incidence of postoperative respiratory impairment for patients after esophagectomy (p < 0.001). Accordingly, esophagectomy patients were characterized by longer ventilation times (p < 0.0001), intensive care unit and total postoperative hospital stays (both p < 0.0001). In conclusion, the postoperative clinical course including respiratory impairment after Ivor Lewis esophagectomy is significantly worse than that after major pulmonary resection. A detailed investigation of the underlying causes is required to improve the outcome of esophagectomy.

Lung decortication in phase III pleural empyema by video-assisted thoracoscopic surgery (VATS)-results of a learning curve study.

BACKGROUND: Pleural empyema (PE) is a devastating disease with a high morbidity and mortality. According to the American Thoracic Society it is graduated into three phases and surgery is indicated in intermediate phase II and organized phase III. In the latter, open decortication of the lung via thoracotomy is the gold standard whereas the evidence for feasibility and safety of a minimally-invasive video-assisted thoracoscopic approach is still poor. METHODS: Retrospective single-center analysis of patients undergoing surgery for phase III PE from 02/2011 to 03/2015 [n=138, including n=130 VATS approach (n=3 of them with bilateral disease) and n=8 open approach]. The learning curve was assessed by grouping those 127 patients with unilateral disease who underwent a video-assisted thoracoscopic approach into two groups: VATS-1 (03/2011 to 06/2012, n=43) and VATS-2 (06/2012 to 03/2015, n=84). RESULTS: ASA-scores (P=0.0279) and rate of pre-operative drainage therapy (P=0.0534) were higher in VATS-2 patients. Operating times were longer in VATS-1 (P=0.0308), intra-operative complication as well as conversion to open surgery rates did both not differ. Rates of post-operative vasoconstrictive therapy (P=0.0191) and prolonged mechanical ventilation (P=0.0560) were both higher in VATS-2, however, post-operative length of stay (LOS) at intensive care unit, overall post-operative LOS and post-operative complication rate were similar in both groups. CONCLUSIONS: Video-assisted thoracoscopic surgery is feasible for evacuation and decortication in late phase III PE. A learning curve of approximately 40 cases is sufficient to gain procedure-specific surgical skills and thus reduce the operating times sufficiently.