Thoracoscopic treatment of pulmonary sequestration

Objective: Pulmonary sequestration is a rare congenital malformation and may be the cause of recurrent infections or hemoptysis. It has been shown in case reports that resection by video-assisted thoracic surgery (VATS) is feasible despite the possible technical difficulties due to inflammatory changes, but its role has not been evaluated yet in a larger series of consecutively treated patients. Methods: Retrospective analysis of all consecutively thoracoscopically treated patients (between January 1991 and January 2005) with pulmonary sequestration in a single center. We included 14 patients in the study who fulfilled the criteria; seven were women. Median age was 33 years (20-64 years). The following data were analyzed for all patients: major symptoms, diagnostic procedures, treatment, and outcome. Operative parameters and findings including operating time, blood loss, anatomical location of the sequestration, and feeding vessels were evaluated. Results: Leading symptoms were recurrent infections (10), hemoptysis (3), and chest discomfort (1). The diagnosis was made by CT scan. Additionally, an arteriography or an angio-MRI was done in three patients and one patient, respectively. Thirteen intralobar (all lower lobes, eight on the right) and one left-sided extralobar pulmonary sequestration were resected. We performed eight lobectomies, four atypical segmentectomies, one extralobar resection, and one occlusion of the aberrant artery. One case had to be converted to a thoracotomy due to bleeding from the aberrant artery. There was no mortality. Complications included pneumonia in three cases, one hemothorax, one pneumothorax after removing the chest tube, and one wound infection. All were treated conservatively. Conclusion: Thoracoscopic treatment of pulmonary sequestration is feasible in experienced hands. The aberrant systemic artery can be freed and dissected safely despite the frequently occurring inflammatory changes. Conversion rate to thoracotomy is lo

Sleeve resections with unprotected bronchial anastomoses are safe even after neoadjuvant therapy†

OBJECTIVES Sleeve resection is the operation of choice in patients with centrally located tumours, in order to avoid a pneumonectomy. Most surgeons protect the bronchial anastomoses with tissue to prevent insufficiencies. The purpose of this study is to report on outcome of unwrapped bronchial anastomoses, especially after neoadjuvant chemo- or chemoradiotherapy. METHODS Between 2000 and 2010, 103 patients [59 years (range 16-80), 40 females] underwent bronchial sleeve resections without coverage of the anastomosis with a tissue flap. We retrospectively reviewed the data for morbidity, mortality and survival, especially with regard to the type of resection, neoadjuvant therapy and stage. RESULTS Sleeve lobectomy was performed in 88, sleeve bilobectomy in 8, sleeve pneumonectomy in 4 and sleeve resection of the main bronchus in 3 patients. Twenty-seven patients had a combined vascular sleeve resection. Neoadjuvant chemotherapy was performed in 20 and radiochemotherapy in 5 patients. Non-small cell lung cancer (NSCLC) was present in 76 patients (squamous cell carcinoma in 44, adenocarcinoma in 24, large cell carcinoma in 6and mixed cell in 2) and neuroendocrine tumour in 20 and other histological types in 7 patients. The pathologic tumour stage in NSCLC was stage I in 26, stage II in 26, stage IIIA in 16, stage IIIB in 7 and stage IV in 1 patient. There were no anastomotic complications, especially no fistulas. One patient developed narrowing of the intermediate bronchus without need for intervention. Twenty-four patients had early postoperative complications, including 11 surgery-related complications (air leakage, nerve injury, haemothorax or mediastinal emphysema). The 30-day mortality was 3% (one patient died due to heart failure and two with multiorgan failure). The 5-year survival rate was 63% in NSCLC patients and 86% in neuroendocrine tumour patients. CONCLUSIONS Sleeve resection without wrapping the bronchial anastomoses with a tissue flap is safe even in patients who underwent neoadjuvant chemo- or chemoradiotherapy. Therefore, wrapping of the bronchial anastomoses is not routinely mandator

Accelerated angiogenesis by continuous medium flow with vascular endothelial growth factor inside tissue-engineered trachea

Objective: To test the effects of a continuous medium flow inside DegraPol® scaffolds on the reepithelialization and revascularization processes of a tissue-engineered trachea prosthesis. Methods: In this proof-of-principle study a continuous medium flow was maintained within a tubular DegraPol® scaffold by an inserted porous catheter connected to a pump system. The impact of the intra-scaffold medium flow on the survival of a tracheal epithelial sheet wrapped around and on chondrocyte delivery to the DegraPol® scaffold was studied. In the chick embryo, chorioallantoic membrane (CAM) model angiogenesis within the biomaterial was investigated. Results: Scanning electronic microscopy (SEM) images showed an intact epithelial layer after a 2-week support by continuous medium flow underneath. On histology, three-dimensional cell growth was detected in the continuous delivery group. The CAM assay showed that angiogenesis was enhanced within the DegraPol® scaffolds when vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) was added to the perfusate. Conclusions: Taken together, these results demonstrated that the built-in perfusion system within DegraPol® scaffolds was able to maintain an intact tracheal epithelial layer, allowed a continuous delivery of cells, and kept an efficient VEGF/VPF expression level which accelerated angiogenic response in the CAM assay. This design combines the in vitro and in vivo parts of tissue engineering and offers the possibility to be used as an in vivo bioreactor implanted for the tissue-engineered reconstruction of trachea and of other organ

Minimally invasive resection of thymomas with the da Vinci® Surgical System†

OBJECTIVES The resection of thymic tumours requires completeness and may be technically challenging due to the anatomical proximity of the delicate mediastinal structures. An open approach by sternotomy is still recommended in all cases with locally extended disease. Video-assisted thoracoscopic surgery is feasible, but limited by the two-dimensional vision and the impaired mobility of the instruments. We evaluated the da Vinci® Surgical System for the resection of various mediastinal pathologies, particularly thymomas. METHODS Among 105 patients operated on by robotic assisted thoracoscopic surgery (RATS) for mediastinal tumours between 27 August 2004 and 12 July 2011, 20 patients with thymomas were studied prospectively. Of these, 10 males with a median age of 53 years, with a well-circumscribed thymic lesion on computed tomography (CT) and a diameter of 6 cm, underwent a hybrid procedure with a contralateral thoracotomy on the side of the main tumour extension. A regular follow-up with chest CT scans was performed every 6 months. RESULTS Thymoma resection was complete in all patients. Partial pericardial resection was needed in five and pulmonary resection in two patients. Eighty-five percent of patients had an R0 resection. Histological classifications included thymoma WHO type A (n = 3), AB (n = 8), B1-2 (n = 5) and B3 (n = 4). All B3 thymomas received adjuvant radiotherapy. No intraoperative complications occurred. The median hospitalization time was 5 days (range 2-14 days). There were no local, but two pleural, recurrences. After a median observation time of 26 months, 19 patients (95%) are alive. CONCLUSIONS Well-circumscribed thymomas can be safely and completely resected with the da Vinci® Surgical System with excellent short- and mid-term outcomes. Selected tumours with large diameters may be resectable using a hybrid procedure combining RATS with a thoracotom

Donor and recipient treatment with the Lazaroid U-74006F do not improve post-transplant lung function in swine

Objective: U-74006F is the only Lazaroid which is currently in clinical use. A number of experimental studies demonstrate that Lazaroids reduce ischemia/reperfusion injury in various organ systems. We evaluated the effect of U-74006F on reperfusion injury in a large animal model of lung allo-transplantation. Methods: Two different treatment modalities were evaluated and compared with corresponding control groups. Unilateral left lung transplantation was performed in 21 weight-matched pigs (24-31 kg). Donor lungs were flushed with 1.5 l cold (1°C) LPD solution and preserved for 20 h. In group I (n=5), donor animals were pretreated with U-74006F (10 mg/kg i.v.) 20 min before harvest. In addition U-74006F was added to the flush solution (10 mg/l). In group III (n=6), the Lazaroid was given to the donor before flush and to the recipient before reperfusion (3 mg/kg i.v.). Group II and IV (n=5) served as control. One hour after reperfusion, the recipient contralateral right pulmonary artery and bronchus were ligated to assess graft function only. Extravascular lung water index (EVLWI), mean pulmonary artery pressure, cardiac output, and gas exchange were assessed during a 5 h observation period. Lipid peroxidation (TBARS) and neutrophil migration (MPO activity) were measured at the end of the assessment in lung allograft tissue. Results: A significant change of TBARS concentration was shown in group III (group III 78.7±4.6 pmol/g vs. group IV 120.8±7.2 pmol/g (P=0.0065) normal lung tissue 41.3±4.2 pmol/g). MPO activity was reduced in group III 3.74±0.25 δOD/mg per min vs. group IV 4.97±0.26 δOD/mg per min (P=0.027), normal lung tissue 1.04±0.27 δOD/mg per min). Pulmonary hemodynamics and gas exchange after reperfusion did not differ between groups. In group I and III, a tendency towards a reduced EVLWI was noted. Conclusion: We conclude that combined treatment of donor and recipient with U-74006F reduces free radical mediated injury in the allograft. However, this intervention did not result in a significant reduction of post-transplant lung edema or improvement of pulmonary hemodynamics. Donor pretreatment alone did not improve lung allograft reperfusion injury. These results indicate that the benefit of U-74006F is too small to consider clinical application in lung transplantatio

Long-Term Outcomes of Cadaveric Lobar Lung Transplantation: An Important Surgical Option

BACKGROUND: Cadaveric lobar lung transplantation (L-LTx) is developed to overcome donor-recipient size mismatch. Controversial short- and long-term outcomes following L-LTx have been reported compared to full-sized lung transplantation (F-LTx). This study reports long-term outcomes after L-LTx. METHODS: We reviewed patients undergoing lung transplantation (LTx) between 2000 and 2016. The decision to perform L-LTx was made based mainly on donor-recipient height discrepancy and visual assessment of donor lungs. Predicted donor-recipient total lung capacity (TLC) ratio was calculated more recently. Primary outcome was overall survival. RESULTS: In all, 370 bilateral LTx were performed during the study period, among those 250 (67%) underwent F-LTx and 120 (32%) underwent L-LTx, respectively. One- and 5-year survival rates were 85% vs. 90% and 53% vs. 63% for L-LTx and F-LTx, respectively (p = 0.16). Chronic lung allograft dysfunction (CLAD)-free survival at 5 years was 48% in L-LTx vs. 51% in F-LTx recipients (p = 0.89), respectively. Age, intraoperative extracorporeal membrane oxygenation (ECMO) use, intensive care unit (ICU) stay, and postoperative renal replacement therapy (RRT) were significant prognostic factors for survival using multivariate analysis. CONCLUSIONS: Overall survival and CLAD-free survival following L-LTx were comparable to F-LTx. Given the ongoing donor organ shortage, cadaveric L-LTx remains as an important resource in LTx

Sildenafil extends survival and graft function in a large animal lung transplantation model

Objective: Restoring intracellular cGMP and inducing NO-synthesis attenuates ischemia-associated early pulmonary allograft dysfunction. Phosphodiesterase-5 (PDE), predominantly expressed in lung tissue, plays a pivotal role in modulating the cGMP/NO-synthase pathway in endothelial and epithelial cells. In this study, we evaluate the effect of employing sildenafil (Viagra®), a specific inhibitor of PDE-5, to counteract ischemia/reperfusion (I/R) injury in a single lung transplantation model of extended ischemia. Methods: Donor animals (weight matched outbred pigs, 28-35 kg) in the treatment group (I) (n = 5) were injected with 0.7 mg sildenafil/kg into the pulmonary artery (PA) prior to inflow occlusion. For perfusion, Perfadex®, containing 0.7 mg sildenafil/l was used, and the graft stored at 1 °C in the perfusion solution. After 24 h ischemia, unilateral left lung transplantation was performed. Starting at reperfusion, group I received continuous sildenafil (0.7 mg sildenafil/kg), over 6 h. Except for the sildenafil application, the control group (II) (n = 4) was treated identically (PGE1 was injected into the PA). One hour after reperfusion, the right main bronchus (MB) and right PA were occluded. Over the next 5 h, cardiopulmonary parameters (systemic aterial, PA, central venous, left atrial pressure, pCO2, pO2) were measured, including extravascular lung water (EVLW). Thiobarbituric acid-reactive substance assay (TBARS) and myeloperoxidase (MPO) analysis from lung tissue were run. Results: All recipients of group I survived the 6-h reperfusion period; in contrast, all control animals died within 1-2 h after occlusion of the right side. In comparison to a marked rise in pulmonary vascular resistance (PVR) in group II (>1000 dyne s cm−5), PVR in group I remained stable, moderately elevated from baseline (baseline: 150-180 dyne s cm−5 vs endpoint: 1000 dyne s cm−5). EVLW in group I did not increase during reperfusion (baseline: 6.75 ± 1.4 mg/kg vs endpoint: 6.7 ± 1.0 mg/kg), in contrast to group II, where pulmonary edema at 2-h reperfusion preceded terminal graft failure (group I: 9.7 ± 0.1 mg/kg vs group II: 6.48 ± 1.8 mg/kg). Tissue reactive free radicals at endpoint measurement in group I did not differ significantly from native tissue. Yet, when compared to specimen taken from group II at time of terminal graft failure, a significant increase in free radicals was noted (group I: 13.8 ± 1.6 pmol/g vs group II: 18.5 ± 3.0 pmol/g, p < 0.05). Conclusion: Sildenafil treatment prevents terminal early graft failure, allowing lung transplantation after 24-h ischemia time. Reperfusion edema was strikingly diminished, preserving pulmonary structural and functional integrity while prolonging graft ischemia time. Employing the established PDE-5 inhibitor sildenafil during lung perfusion, storage, and implantation, ischemic tolerance may be extended and early graft function improve

Extended donor lungs: eleven years experience in a consecutive series

Objective: The aim of this study was to delineate the profile of extended donor lungs in comparison to ideal donor lungs and to analyse their outcome. Particular attention was given to donor lungs with a low PaO2 (≪250mmHg) before harvesting or with multiple extended criteria. Methods: Between 1993 and 2003, 148 patients (79 women, 69 men, mean age 39.9 years) underwent lung transplantation. Indications were cystic fibrosis in 35.8%, emphysema in 26.4%, pulmonary fibrosis in 12.2%, pulmonary hypertension in 9.5%, and others in 16.1%. Donor data and recipients medical files were reviewed. Criteria for donor lungs were considered extended if one or more of the following criteria were met: age ≫55 years, smoking ≫20 pack-years, PaO2 before harvesting ≪300mmHg, pathologic chest X-ray, and purulent secretion at bronchoscopy. A comparison between recipients from ideal and from extended donor lungs was performed with respect to the median duration of mechanical ventilation, the median length of stay at the intensive care unit, postoperative complications, the 30-day and the 1-year survival, and the 6-month follow-up spirometry. Results: Sixty-three (42.6%) donor lungs were considered extended and 20 (31.7%) met more than one criteria. Outcome comparison between recipients from ideal (I) and extended (II) donor lungs did not statistically differ in postoperative complications (18.8% (I) vs. 26.9% (II), P=0.32), mean duration of mechanical ventilation (d) (4.4±2.7 (I) vs. 2.6±2.1 (II), P=0.2), mean length of stay at the ICU (d) (11.5±8.8 (I) vs. 9.2±6.9 (II), P=0.4), 6-month pulmonary function (FEV1=83±23% of the predicted value (I) vs. 82±18% (II), P=0.81), 30-day survival (90.6% (I) vs. 93.7% (II), P=0.56), 1-year survival (83.5% (I) vs. 81% (II), P=0.83). Thirty-day survival was also comparable even in recipients from donor lungs with PaO2≪250mmHg (n=8) (90.6% (I) vs. 87.5%, P=0.57). The number of extended criteria had no impact on the outcome. The combination of PaO2≪300mmHg with purulent secretion at bronchoscopy seemed to influence the early outcome of recipients from extended donor lungs negatively. Conclusions: Our results suggest that the use of selected extended donor lungs does not compromise the outcome after transplantation. PaO2 ≪250mmHg before harvesting of the lungs is not an absolute contra-indication for transplantatio

Survival and graft function in a large animal lung transplant model after 30 h preservation and substitution of the nitric oxide pathway

Objective: Substitution of the nitric oxide- (NO-) pathway improves early graft function following lung transplantation. We previously demonstrated that 8-Br-cGMP (second messenger of NO) to the flush solution and tetrahydrobiopterin (BH4, coenzyme of NO synthase) given as additive during reperfusion improve post-transplant graft function. In the present study, the combined treatment with 8-Br-cGMP and BH4 was evaluated. Methods: Unilateral left lung transplantation was performed in weight matched outbred pigs (24-31kg). In group I, grafts were preserved for 30h (n=5). 8-Br-cGMP (1mg/kg) was added to the flush solution (Perfadex™, 1.5l, 1°C) and BH4 (10mg/kg/h) was given to the recipient for 5h after reperfusion. In group II, lungs were transplanted after a preservation time of 30h (n=3) and prostaglandin E1 (250g) was given into the pulmonary artery (PA) prior to flush. In all recipients 1h after reperfusion the contralateral right PA and bronchus were ligated to assess graft function only. Survival time after reperfusion, extravascular lung water index (EVLWI), hemodynamic variables, and gas exchange (PaO2) were assessed during a 12h observation period. Results: All recipients in group I survived the 12h assessment, whereas none of the group II animals survived more than 4h after reperfusion with a rapid increase of EVLWI up to 24.8±6.7ml/kg. In contrast, in group I EVLWI reached up to 8.9±1.5ml/kg and returned to nearly normal levels at 12h (6.1±0.8ml/kg). In two animals of group I the gas exchange deteriorated slightly. The other three animals showed normal arterial oxygenation over the entire observation time. Conclusion: Our data indicate that the combined substitution of the NO pathway during preservation and reperfusion reduces ischemia/reperfusion injury substantially and that this treatment even allows lung transplantation after 30h preservation in this mode

Local recurrence model of malignant pleural mesothelioma for investigation of intrapleural treatment

Objective: Local recurrence remains a major problem in the treatment of malignant pleural mesothelioma. The aim of the underlying study was to establish a standardised local recurrence model in rats which enables to study different intrapleural therapies. Materials and methods: Fifty microlitre containing 1×106 cells of a syngeneic rat malignant mesothelioma cell line (II-45), established from mesothelioma in Fischer 344 rats exposed to asbestos, were inoculated subpleurally via a left-sided thoracotomy. Tumour size was assessed 6 days later and the tumour nodule completely resected. Evaluation of recurrence at the resection site was performed after 10 days (n=6) and 6 days (n=6). The recurrent nodule was histopathologically confirmed. In a second experiment, this new recurrence model was evaluated for the effect of intrapleural therapy with different agents: 4ml of cisplatin-solution (100mg2/kg BW), cisplatin combined with the fibrin-based sealant Vivostat®, 4ml taurolidine 2%, repeated injection of 1μg of the chemokine CCL-19 at the tumour site and 4ml povidone-iodine in a dilution 1:10. In a control group, the chest cavity was filled with 4ml 0.9% NaCl. The primary endpoint was the extent of tumour recurrence. Results: Six days after inoculation, all animals presented a standardised tumour nodule at the injection site of a mean diameter of 5.1 (±0.8)mm. Evaluation of the recurrence after 10 days showed a relapse directly at the resection site, but additional tumour nodules on the ipsi- and contralateral chest wall were found and histologically confirmed. The animals that were sacrificed 6 days after resection of the tumour nodule showed a recurrence only at the resection site with no macroscopic or microscopic evidence of other tumour. Resection of the tumour nodule combined with intrapleural application of the different agents lead to clear reduction of recurrence. The strongest effect was observed after intrapleural application of cisplatin-Vivostat® with significant decrease of the longest, widest and thickest diameter of the recurrence. Conclusions: With this new recurrence model for investigation of malignant pleural mesothelioma in rats, we were able to investigate new intrapleural therapies after pneumonectomy. The intrapleural application of cisplatin-Vivostat® significantly reduced the extent of local recurrenc