Minimally invasive video-endoscopic sympathectomy by use of a transaxillary single port approach

Objectives: This is a prospective study to evaluate the long-term outcome and the value of a transaxillary single port thoracic sympathectomy by use of a modified paediatric cystoresectoscope in a consecutive series of patients with facial blushing and/or hyperhidrosis. Materials and methods: All patients who underwent a thoracic transsection of the sympathetic chain from T2 to T5 by use of a 7-mm single port approach and a modified urologic electroresectoscope between 1996 and 1998 were prospectively analysed regarding postoperative morbidity and outcome (clinical evaluation, visual analogue scale) in order to validate this technique. Results: 37 patients (18 men, 19 women) with an age ranging from 18 to 67 years (mean 34 years) underwent 74 bilateral video-assisted thoracic sympathectomies. The indications for sympathectomy included facial blushing in 32%, hyperhidrosis in 52%, or both in 16% of the patients. Ninety-five percent of the patients were discharged from the hospital on the next day, the 30-day mortality was zero, and there was no conversion to an open procedure. A severe complication with crossed emboli and motor aphasia was noted. A unilateral transient Horner's syndrome was observed in two patients. Three-month follow-up revealed an excellent cosmetic and functional result, with no residual pain. Complete relief of symptoms was observed in 89% and in 100% of the patients with facial blushing and palmar hyperhidrosis, respectively, after a follow-up of 34.5 months. Recurrence of the symptoms after initial regression was noted in 5.7% of the patients 3 years after surgery. Compensatory sweating of the lower extremities was significantly increased in patients with hyperhidrosis and facial blushing; however, sweating of the trunk was only increased in patients with hyperhidrosis. Improvement of quality of life was observed in 94.6% of the patients. Conclusions: Single port thoracoscopic sympathectomy by use of a modified paediatric cystoresectoscope and transsection from T2 to T5 gives an excellent cosmetic and functional outcome, with better results in patients with hyperhidrosi

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

Minimally invasive video-endoscopic sympathectomy by use of a transaxillary single port approach.

OBJECTIVES: This is a prospective study to evaluate the long-term outcome and the value of a transaxillary single port thoracic sympathectomy by use of a modified paediatric cystoresectoscope in a consecutive series of patients with facial blushing and/or hyperhidrosis. MATERIALS AND METHODS: All patients who underwent a thoracic transsection of the sympathetic chain from T2 to T5 by use of a 7-mm single port approach and a modified urologic electroresectoscope between 1996 and 1998 were prospectively analysed regarding postoperative morbidity and outcome (clinical evaluation, visual analogue scale) in order to validate this technique. RESULTS: 37 patients (18 men, 19 women) with an age ranging from 18 to 67 years (mean 34 years) underwent 74 bilateral video-assisted thoracic sympathectomies. The indications for sympathectomy included facial blushing in 32%, hyperhidrosis in 52%, or both in 16% of the patients. Ninety-five percent of the patients were discharged from the hospital on the next day, the 30-day mortality was zero, and there was no conversion to an open procedure. A severe complication with crossed emboli and motor aphasia was noted. A unilateral transient Horner's syndrome was observed in two patients. Three-month follow-up revealed an excellent cosmetic and functional result, with no residual pain. Complete relief of symptoms was observed in 89% and in 100% of the patients with facial blushing and palmar hyperhidrosis, respectively, after a follow-up of 34.5 months. Recurrence of the symptoms after initial regression was noted in 5.7% of the patients 3 years after surgery. Compensatory sweating of the lower extremities was significantly increased in patients with hyperhidrosis and facial blushing; however, sweating of the trunk was only increased in patients with hyperhidrosis. Improvement of quality of life was observed in 94.6% of the patients. CONCLUSIONS: Single port thoracoscopic sympathectomy by use of a modified paediatric cystoresectoscope and transsection from T2 to T5 gives an excellent cosmetic and functional outcome, with better results in patients with hyperhidrosis

Bronchoscopic radioisotope injection for sentinel lymph-node mapping in potentially resectable non-small-cell lung cancer

Objective: Prospective study to evaluate the feasibility of a preoperative bronchoscopic radioisotope application, followed by conventional sentinel lymph-node (SLN) identification and to investigate the occurrence and distribution of micrometastases in relation to SLN activity. Methods: Twenty patients with a mean age of 63 years and proven clinical stage T1-3 N0-1 non-small-cell lung cancer (NSCLC) were included. A dosage of 80 MBq radiolabeled technetium-99m nanocolloid was endoscopically administrated on intubated patients in the operation theatre. At thoracotomy, scintigraphic readings of both the primary tumor and hilar and mediastinal lymph-node stations were obtained with a hand-held gamma-counter. Patients underwent lung resection and mediastinal lymphadenectomy. Radiolabeled nodes were also examined separately on back-table. SLNs were defined as the hottest nodes or nodes with at least one-tenth of the radioactivity of the hottest nodes. SLNs pathologic assessment included standard examination using hematoxylin and eosin staining on step sections and immunohistochemistry (ICH) for cytokeratins. Results: Identification of SLNs was possible in 19/20 (95%) patients after bronchoscopic radioisotope application. In 7/19 (37%) patients, a unique SLN was identified, whereas in 12/19 (63%) patients, nodes from two different stations could be classified as SLNs. Metastatic nodal disease was found in 9/19 (47%) patients. ICH revealed micrometastases in 2/12 (17%) patients, initially classified nodal negative. Pathologic negative SLNs were a predictor for absence of metastatic nodal disease after mediastinal lymphadenectomy. No complication related to the procedure was observed. Conclusion: Our preliminary results suggest that preoperative bronchoscopic radioisotope injection for SLN identification is a safe and simple method, improving accuracy of SLN detection in comparison to intraoperative technique. The absence of metastases in the SLNs seems to predict a negative nodal status accuratel

2OACTIVATION OF T CELLS UPON TREATMENT WITH BISPECIFIC ANTIBODIES CORRELATES WITH THE EXPRESSION OF CO-INHIBITORY RECEPTORS ON TUMOR-INFILTRATING LYMPHOCYTES IN HUMAN LUNG CANCER

Introduction: T cell bispecific antibodies (TCB) are designed to recruit and simultaneously activate T cells against target cells such as tumor cells expressing a particular surface antigen. However, it is currently unknown how immuno-modulatory mechanisms active in the tumor microenvironment such as the expression of T cell co-inhibitory receptors may influence the therapeutic effect of TCBs. Methods: We performed a comprehensive phenotypic analysis of tumor infiltrating immune cells from lung carcinoma digests by multicolour flow cytometry. In particular, expression of T cell co-inhibitory and -stimulatory receptors was analyzed. Tumor digests were treated with catumaxomab, a TCB directed against CD3 and EpCAM. T cell activation and effector functions were assessed upon exposure to catumaxomab. Results: CD8+ T cells in lung carcinoma showed a broad heterogeneity in expression of the T cell co-inhibitory receptors PD-1, Tim-3, CTLA-4, Lag-3 and BTLA. Tumor stage and nodal status correlated with number and intensity of expressed receptors. Upon exposure to catumaxomab, a considerable heterogeneity in T cell activation among different tumors was observed. Of note, T cells expressing high levels and multiple co-inhibitory receptors were more impaired in their activation and effector functions after treatment with catumaxomab indicating a higher level of exhaustion. In a further analysis of CD8+ TIL subsets we found that BTLA+ T cells expressed more additional inhibitory receptors than all other subsets, namely PD-1, Tim-3, CTLA-4 and Lag-3, whereas only a small part of PD-1+ T cells expressed another receptor. Tim-3+ T cells usually co-expressed PD-1, but multiple receptors were found only on a low number of cells. Conclusion: In summary, our data suggest that the activity of TCBs is largely affected by the expression of T cell co-inhibitory receptors on tumor-infiltrating immune cells. Furthermore, these data provide a clinical rationale for combining bispecific antibodies with compounds which antagonize T cell exhaustion. Disclosure: D. Thommen, J. Schreiner, P. Herzig, P. Mueller and A. Zippelius: received research funding from Roche Glycart; V. Karanikas: is employed by Roche Glycart. All other authors have declared no conflicts of interes

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

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

Airway complications after lung transplantation: risk factors, prevention and outcome

PURPOSE: Anastomotic complications following lung transplantation (LuTx) have been described in up to 15% of patients. Challenging to treat, they are associated with high morbidity and a mortality rate of 2-5%. The aim of this study was to analyze the incidence of complications in a consecutive series of bronchial anastomosis after LuTx at our center and to delineate the potential risk factors. METHODS: Between 1992 and 2007, 441 bronchial anastomoses were performed in 235 patients. Indications for transplantation were cystic fibrosis (35.7%) emphysema (28.1%) pulmonary fibrosis (12.8%) and pulmonary hypertension (7.7%). There were 206 sequential bilateral and 28 single transplants including lobar engraftments in 20 cases. The donor bronchus was shortened to the plane of the lobar carina including the medial wall of the intermediate bronchus. Peribronchial tissue was left untouched. Anastomosis was carried out using a continuous absorbable running suture (PDS 4/0) at the membranous and interrupted sutures at the cartilaginous part. Six elective surveillance bronchoscopies were done monthly during the first half-year post-LuTx, with detailed assessment of the pre- and post-anastomotic airways. RESULTS: One-year survival since 2000 was 90.5%. In all 441 anastomoses performed, no significant dehiscence was observed. In one patient, a small fistula was detected and closed surgically on postoperative day five. Fungal membranes were found in 50% of the anastomoses at 1 month and in 14% at 6 months. Discrete narrowing of the anastomotic lumen without need for intervention was found in 4.9% of patients at 1 month and in 2.4% at 6 months. Age, cytomegalovirus status, induction therapy, immunosuppressive regimen, ischemic time, and ventilation time had no influence on bronchial healing. CONCLUSIONS: Clinically relevant bronchial anastomotic complications after LuTx can be avoided by use of a simple standardized surgical technique. Aggressive antibiotic and antifungal therapy might play an important supportive rol

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

A comparative evaluation of intrathoracic latissimus dorsi and serratus anterior muscle transposition.

BACKGROUND: Comparison of intrathoracic latissimus dorsi (LD) versus serratus anterior (SA) muscle transposition for treatment of infected spaces, broncho-pleural fistulae, and for prophylactic reinforcement of the mediastinum after extended resections following induction therapy. PATIENTS AND METHODS: Twenty LD and 17 SA transfers were performed for prophylactic reinforcement (11 LD; nine SA), and treatment of infections (nine LD; eight SA) from 1995 to 1998. RESULTS: The 30-day mortality was 0% following prophylactic reinforcement and 29% following treatment of infections (three LD; two SA). Prophylactic mediastinal reinforcement was successful in 11 of 11 patients with LD and nine of nine with SA transpositions, and treatment of infected spaces in eight of nine patients with LD and two of three with SA transfers. Morbidity requiring re-intervention consisted of flap necrosis (one LD), bleeding (one SA), and skin necrosis over a winged scapula (one SA). Subcutaneous seromas and chest wall complaints were more frequent following LD (45 and 36%, respectively) compared with SA transfers (29 and 27%, respectively), whereas impaired shoulder girdle function was more frequent after SA than after LD transfer (27 vs. 21%). CONCLUSION: Intrathoracic LD and SA muscle transpositions are both efficient for the prevention or control of infections following complex thoracic surgery, and are both associated with similar and acceptable morbidity and long-term sequelae