Video-assisted thoracic surgery: Risks and benefits

Summary: Background: Thoracoscopy has been used throughout this century, especially in the treatment of pleural disease. The introduction of video-assistance and especially designed instruments such as stapling devices in 1992 led to a worldwide and enthusiastic application for the treatment of a variety of thoracic pathologies. Methods: This report summarizes our experience gained from 1013 consecutive VATS procedures performed since 1990 for various indications in order to clarify its role for surgery of thoracic pathologies. Results: 234 patients underwent VATS for pleural biopsy, 154 for talcage, 163 for pulmonary wedge resections in order to clarify interstitial diseasee or indetermined nodules, 126 for spontaneous pneumothorax, 91 for decortication of empyema, 63 for symphatectomy, 55 for biopsy of mediastinal lesions, 29 for pericardial effusions (fenestration), 25 for lung volume reduction surgery, 17 for excision of mediastinal cysts and 12 for excision of neurogenic tumors of the posterior mediastinum. Conclusions: Our results demonstrate that VATS has gained established acceptance for several indications, however, caution in application of VATS is clearly indicated for some diseases, especially for thoracic malignancie

Modeling the Aqueous-Phase Copper Ion-Exchange Behavior onto SSZ-13 Zeolites

Copper-exchanged zeolites are utilized as catalysts for the selective catalytic reduction of nitrogen oxides, which are atmospheric pollutants found in diesel engine exhaust. The total amount of copper ions and the types of copper species (Cu(II) or Cu(II)OH) exchanged onto a zeolite can be varied. Copper is exchanged onto SSZ-13 (an aluminosilicate zeolite with the chabazite topology) during a process known as aqueous ion exchange, where the zeolite is mixed in a copper-containing solution. The distribution of copper on SSZ-13 is influenced by exchange conditions, including the molarity, temperature, and pH of the copper solution. The effect of exchange conditions on the amount and type of copper exchanged onto SSZ-13 has not been thoroughly investigated. In order to study these effects, ion exchange experiments were performed with solutions containing different copper concentrations and pHs. The copper loading (wt%) of each SSZ-13 sample was determined by atomic absorption spectroscopy (AAS). Data from AAS shows that SSZ-13 samples exchanged in solutions with higher copper molarities have higher copper loadings. Further exchanges are being done to test the effects of pH on the amount and type of copper species exchanged onto SSZ-13 through characterization by AAS and temperature programmed desorption (TPD). Using the collected data, a model will be developed to predict the amount and distribution of copper on SSZ-13 based on the exchange conditions

Pulmonary function testing after operative stabilisation of the chest wall for flail chest

Objective: This is a prospective evaluation of chest wall integrity and pulmonary function in patients with operative stabilisation for flail chest injuries. Methods: From 1990 to 1999, 66 patients (56 men, 10 women; mean age 52.6 years) with antero-lateral flail chest (≧4 ribs fractured at ≧2 sites) underwent surgical stabilisation using reconstruction plates. Clinical assessment and pulmonary function testing were performed at 6 months following surgery. Results: Fifty-five (83%) patients had various combinations of injuries of the thorax, head, abdomen and extremities. Sixty-three (95.5%) patients underwent unilateral and 3 (4.5%) patients bilateral stabilisation with a median delay of 2.8 days (range 0-21 days) from admission. The 30-day mortality was 11% (seven of 66 patients). Immediate postoperative extubation was feasible in 31 of 66 patients (47%) and extubation within 7 days following stabilisation in 56 of 66 patients (85%). No plate dislocation was observed during the follow-up. The shoulder girdle function was intact in 51 of 57 patients (90%). Chest wall complaints were noted in 6 of 57 (11%) patients, requiring removal of implants in three cases. All patients returned to work within a mean period of 8 (range 3-16) weeks following discharge. Pulmonary function testing (n=50) at 6 months after the operation revealed a significant difference of predicted vs. recorded vital capacity (VC) and forced expiratory volume in 1s (FEV1) (P=0.04 and P=0.0001, respectively; Wilcoxon signed-rank test). The median ratio of the recorded and predicted total lung capacity (TLC) was shown to be significantly higher than 0.85 (P=0.0002; Wilcoxon signed-rank test), indicating prevention of pulmonary restriction. Conclusion: Antero-lateral flail chest injuries accompanied by respiratory insufficiency can be effectively stabilised using reconstruction plates. Early restoration of the chest wall integrity and respiratory pump function may be cost effective through the prevention of prolonged mechanical ventilation and restriction-related working incapacit

Non-steroidal anti-inflammatory drugs decrease the quality of pleurodesis after mechanical pleural abrasion

Objective: Non-steroidal anti-inflammatory drugs (NSAIDs) are often applied for pain management after thoracic surgery. Since these drugs diminish collagen deposition through inhibition of the prostaglandin synthesis, we investigated their effects on adhesion formation after endoscopic mechanical pleural abrasion, which is often applied in the therapy of pneumothorax. Methods: Mechanical pleural abrasion was performed unilaterally by the use of video-assisted thoracoscopic surgery technique in an established pig model. Ten animals (41.3±3.4 kg) were divided into a treatment group and a control group. In the treatment group, animals received 100 mg diclofenac (2 mg/kg body weight) orally daily for 3 weeks after surgery. At 3 weeks, all animals were sacrificed and efficacy of pleurodesis was macroscopically assessed by three independent reviewers blinded to the treatment of animals using a five-point severity pleurodesis score (from 0, no adhesions to 4, complete symphisis) and obliteration grade rating the distribution of adhesions (from 0, no adhesions to 4, adhesions in the whole chest). Microscopic evaluation was performed by two pathologists blinded to the study groups as well. A four-point score assessed the amount of collagen deposition (from 1, a few collagen fibers to 4, scar). Results: Gross observation showed more dense adhesions in control animals with a median pleurodesis score of 3.67±1.0 in comparison to 2±2.2 in the treatment group (P=0.01*, Mann-Whitney non-parametric test). Distribution of adhesions was comparable in both groups with a median obliteration score of 3.67±1.3. Histopathologic examination showed a higher amount of collagen deposition in the control group, suggesting more dense adhesions, whereas in the treatment group there was loose granulation tissue (score of 4.0±0.8 vs. 2.3±1.0 in the treatment group, P=0.06). The degree of inflammatory reaction was comparable in the two groups. Conclusions: Our results demonstrate that perioperative use of NSAIDs highly affects the quality of pleural adhesions obtained after mechanical abrasion in this pig model, which further suggests that these drugs should be avoided for pain management when a pleurodesis is performe

Morbidity and validity of the hemiclamshell approach for thoracic surgery.

OBJECTIVE: This is a prospective study to evaluate the indications and outcome of the hemiclamshell incision (longitudinal partial sternotomy combined with an antero-lateral thoracotomy) as used for a consecutive series of patients requiring surgery for various thoracic pathologies not ideally approached by postero-lateral thoracotomy, sternotomy or thoracoscopy. METHODS: All patients with a hemiclamshell incision performed between 1994 and 1998 were prospectively analyzed regarding indications, postoperative morbidity and outcome (clinical examination and pulmonary function testing) in order to validate this incision for thoracic surgery. RESULTS: 25 patients (15 men, 10 women) with an age ranging from 16 to 73 years (mean 43 years) underwent a hemiclamshell incision. The indications for the hemiclamshell approach were (1) chest trauma with massive hemorrhage requiring urgent access to the mediastinum and the ipsilateral pleural space (40%), (2) tumors of the anterior cervico-thoracic junction with suspicion of vascular involvement (28%) and (3) lesions involving both one chest cavity and the mediastinum (32%). The 30-day mortality was 8%. One patient suffered a sternal wound infection, mediastinitis and pleural empyema after a gun shot wound, whereas wound healing was uneventful in all other patients. Analgesic requirements for postoperative pain relief were not increased as compared to those following a standard thoracotomy. At 3 months normal sensitivity of the entire chest wall and intact shoulder girdle function was noted in 90% of the patients. Pulmonary function testing showed no restriction due to the hemiclamshell incision. CONCLUSIONS: The hemiclamshell incision is a useful approach in selected patients and does not cause more morbidity or long-term sequelae than a standard thoracotomy

Pulmonary function testing after operative stabilisation of the chest wall for flail chest.

OBJECTIVE: This is a prospective evaluation of chest wall integrity and pulmonary function in patients with operative stabilisation for flail chest injuries. METHODS: From 1990 to 1999, 66 patients (56 men, 10 women; mean age 52.6 years) with antero-lateral flail chest (> or =4 ribs fractured at > or =2 sites) underwent surgical stabilisation using reconstruction plates. Clinical assessment and pulmonary function testing were performed at 6 months following surgery. RESULTS: Fifty-five (83%) patients had various combinations of injuries of the thorax, head, abdomen and extremities. Sixty-three (95.5%) patients underwent unilateral and 3 (4.5%) patients bilateral stabilisation with a median delay of 2.8 days (range 0-21 days) from admission. The 30-day mortality was 11% (seven of 66 patients). Immediate postoperative extubation was feasible in 31 of 66 patients (47%) and extubation within 7 days following stabilisation in 56 of 66 patients (85%). No plate dislocation was observed during the follow-up. The shoulder girdle function was intact in 51 of 57 patients (90%). Chest wall complaints were noted in 6 of 57 (11%) patients, requiring removal of implants in three cases. All patients returned to work within a mean period of 8 (range 3-16) weeks following discharge. Pulmonary function testing (n=50) at 6 months after the operation revealed a significant difference of predicted vs. recorded vital capacity (VC) and forced expiratory volume in 1s (FEV1) (P=0.04 and P=0.0001, respectively; Wilcoxon signed-rank test). The median ratio of the recorded and predicted total lung capacity (TLC) was shown to be significantly higher than 0.85 (P=0.0002; Wilcoxon signed-rank test), indicating prevention of pulmonary restriction. CONCLUSION: Antero-lateral flail chest injuries accompanied by respiratory insufficiency can be effectively stabilised using reconstruction plates. Early restoration of the chest wall integrity and respiratory pump function may be cost effective through the prevention of prolonged mechanical ventilation and restriction-related working incapacity

5PMICROTUBULE-DEPOLYMERIZING AGENTS USED IN ANTIBODY-DRUG-CONJUGATES INDUCE ANTITUMOR ACTIVITY BY STIMULATION OF DENDRITIC CELLS

Antibody drug conjugates (ADCs) are emerging as powerful treatment strategies with outstanding target specificity and high therapeutic activity in cancer patients. While >30 ADCs are currently being investigated in clinical trials, brentuximabvedotin and T-DM1 represent clinically approved ADCs in cancer patients. We hypothesized that their sustained clinical responses could be related to the stimulation of an antitumor immune response. Indeed, the two microtubule-destabilizing agents Dolastatin 10 and Ansamitocin P3, from which the cytotoxic components of brentuximabvedotin and T-DM1 are derived, may serve as prototypes for a class of agents that induce tumor cell death and convert tumor resident, tolerogenic dendritic cells (DCs) into efficient antigen presenting cells (APCs). The two drugs induced phenotypic and functional maturation of murine splenic as well as human monocyte-derived DCs. In contrast, microtubule-stabilizing agents such as taxanes did not display this feature. In tumor models, both Dolastatin 10 and Ansamitocin P3 efficiently promoted antigen uptake and migration of tumor-resident DCs to tumor-draining lymph nodes, thereby potentiating tumor-specific T cell responses. Underlining the requirement of an intact host immune system for the full therapeutic benefit of these two compounds, their antitumor effect was far less pronounced in mice lacking adaptive immunity or dendritic cells. Combinations with immune checkpoint inhibition (anti-CTLA-4/-PD-1) did further augment antitumor immunity and tumor rejection, which was reflected by reduced Treg numbers and elevated effector function of tumor resident T cells. Ultimately, we were able to demonstrate peripheral immune cell activation and brisk T cell infiltration into tumors in patients previously treated with BrentuximabVedotin. Experiments are currently ongoing to investigate the immunological mode of action of T-DM1 using orthotopic breast cancer models and patients undergoing treatment. Our data reveal a novel mode of action for microtubule-depolymerizing agents and provide a strong rationale for clinical treatment regimens combining these with immune-based therapies. Disclosure: All authors have declared no conflicts of interes

Engineering tyrosine-based electron flow pathways in proteins: The case of aplysia myoglobin

Tyrosine residues can act as redox cofactors that provide an electron transfer ("hole-hopping") route that enhances the rate of ferryl heme iron reduction by externally added reductants, for example, ascorbate. Aplysia fasciata myoglobin, having no naturally occurring tyrosines but 15 phenylalanines that can be selectively mutated to tyrosine residues, provides an ideal protein with which to study such through-protein electron transfer pathways and ways to manipulate them. Two surface exposed phenylalanines that are close to the heme have been mutated to tyrosines (F42Y, F98Y). In both of these, the rate of ferryl heme reduction increased by up to 3 orders of magnitude. This result cannot be explained in terms of distance or redox potential change between donor and acceptor but indicates that tyrosines, by virtue of their ability to form radicals, act as redox cofactors in a new pathway. The mechanism is discussed in terms of the Marcus theory and the specific protonation/deprotonation states of the oxoferryl iron and tyrosine. Tyrosine radicals have been observed and quantified by EPR spectroscopy in both mutants, consistent with the proposed mechanism. The location of each radical is unambiguous and allows us to validate theoretical methods that assign radical location on the basis of EPR hyperfine structure. Mutation to tyrosine decreases the lipid peroxidase activity of this myoglobin in the presence of low concentrations of reductant, and the possibility of decreasing the intrinsic toxicity of hemoglobin by introduction of these pathways is discussed. © 2012 American Chemical Society

Multicenter trial of neo-adjuvant chemotherapy followed by extrapleural pneumonectomy in malignant pleural mesothelioma

Background: The aim of this multicenter trial was to prospectively evaluate neo-adjuvant chemotherapy followed by extrapleural pneumonectomy (EPP) and radiotherapy, including quality of life as outcome. Patients and methods: Eligible patients had malignant pleural mesothelioma of all histological types, World Health Organization performance status of zero to two and clinical stage T1-T3, N0-2, M0 disease considered completely resectable. Neo-adjuvant chemotherapy consisted of three cycles of cisplatin and gemcitabine followed by EPP. Postoperative radiotherapy was considered for all patients. Results: In all, 58 of 61 patients completed three cycles of neo-adjuvant chemotherapy. Forty-five patients (74%) underwent EPP and in 37 patients (61%) the resection was complete. Postoperative radiotherapy was initiated in 36 patients. The median survival of all patients was 19.8 months [95% confidence interval (CI) 14.6-24.5]. For the 45 patients undergoing EPP, the median survival was 23 months (95% CI 16.6-32.9). Psychological distress showed minor variations over time with distress above the cut-off score indicating no morbidity with 82% (N = 36) at baseline and 76% (N = 26) at 3 months after surgery (P = 0.5). Conclusions: The observed rate of operability is promising. A median survival of 23 months for patients undergoing EPP compares favourably with the survival reported from single center studies of upfront surgery. This approach was not associated with an increase in psychological distres