Thorsten Krueger

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.

Prognostic relevance of Masaoka and Müller-Hermelink classification in patients with thymic tumors

BACKGROUND To compare the prognostic relevance of Masaoka and Müller-Hermelink classifications. METHODS We treated 71 patients with thymic tumors at our institution between 1980 and 1997. Complete follow-up was achieved in 69 patients (97%) with a mean follow up-time of 8.3 years (range, 9 months to 17 years). RESULTS Masaoka stage I was found in 31 patients (44.9%), stage II in 17 (24.6%), stage III in 19 (27.6%), and stage IV in 2 (2.9%). The 10-year overall survival rate was 83.5% for stage I, 100% for stage IIa, 58% for stage IIb, 44% for stage III, and 0% for stage IV. The disease-free survival rates were 100%, 70%, 40%, 38%, and 0%, respectively. Histologic classification according to Müller-Hermelink found medullary tumors in 7 patients (10.1%), mixed in 18 (26.1%), organoid in 14 (20.3%), cortical in 11 (15.9%), well-differentiated thymic carcinoma in 14 (20.3%), and endocrine carcinoma in 5 (7.3%), with 10-year overall survival rates of 100%, 75%, 92%, 87.5%, 30%, and 0%, respectively, and 10-year disease-free survival rates of 100%, 100%, 77%, 75%, 37%, and 0%, respectively. Medullary, mixed, and well-differentiated organoid tumors were correlated with stage I and II, and well-differentiated thymic carcinoma and endocrine carcinoma with stage III and IV (p < 0.001). Multivariate analysis showed age, gender, myasthenia gravis, and postoperative adjuvant therapy not to be significant predictors of overall and disease-free survival after complete resection, whereas the Müller-Hermelink and Masaoka classifications were independent significant predictors for overall (p < 0.05) and disease-free survival (p < 0.004; p < 0.0001). CONCLUSIONS The consideration of staging and histology in thymic tumors has the potential to improve recurrence prediction and patient selection for combined treatment modalities.

Closure of large intrathoracic airway defects using extrathoracic muscle flaps

BACKGROUND Prospective assessment of pedicled extrathoracic muscle flaps for the closure of large intrathoracic airway defects after noncircumferential resection in situations where an end-to-end reconstruction seemed risky (defects of > 4-cm length, desmoplastic reactions after previous infection or radiochemotherapy). METHODS From 1996 to 2001, 13 intrathoracic muscle transpositions (6 latissimus dorsi and 7 serratus anterior muscle flaps) were performed to close defects of the intrathoracic airways after noncircumferential resection for tumor (n = 5), large tracheoesophageal fistula (n = 2), delayed tracheal injury (n = 1) and bronchopleural fistula (n = 5). In 2 patients, the extent of the tracheal defect required reinforcement of the reconstruction by use of a rib segment embedded into the muscle flap followed by temporary tracheal stenting. Patient follow-up was by clinical examination bronchoscopy and biopsy, pulmonary function tests, and dynamic virtual bronchoscopy by computed tomographic (CT) scan during inspiration and expiration. RESULTS The airway defects ranged from 2 x 1 cm to 8 x 4 cm and involved up to 50% of the airway circumference. They were all successfully closed using muscle flaps with no mortality and all patients were extubated within 24 hours. Bronchoscopy revealed epithelialization of the reconstructions without dehiscence, stenosis, or recurrence of fistulas. The flow-volume loop was preserved in all patients and dynamic virtual bronchoscopy revealed no significant difference in the endoluminal cross surface areas of the airway between inspiration and expiration above (45 +/- 21 mm(2)), at the site (76 +/- 23 mm(2)) and below the reconstruction (65 +/- 40 mm(2)). CONCLUSIONS Intrathoracic airway defects of up to 50% of the circumference may be repaired using extrathoracic muscle flaps when an end-to-end reconstruction is not feasible.

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.

A validated assay for measuring doxorubicin in biological fluids and tissues in an isolated lung perfusion model: matrix effect and heparin interference strongly influence doxorubicin measurements

Doxorubicin is an antineoplasic agent active against sarcoma pulmonary metastasis, but its clinical use is hampered by its myelotoxicity and its cumulative cardiotoxicity, when administered systemically. This limitation may be circumvented using the isolated lung perfusion (ILP) approach, wherein a therapeutic agent is infused locoregionally after vascular isolation of the lung. The influence of the mode of infusion (anterograde (AG): through the pulmonary artery (PA); retrograde (RG): through the pulmonary vein (PV)) on doxorubicin pharmacokinetics and lung distribution was unknown. Therefore, a simple, rapid and sensitive high-performance liquid chromatography method has been developed to quantify doxorubicin in four different biological matrices (infusion effluent, serum, tissues with low or high levels of doxorubicin). The related compound daunorubicin was used as internal standard (I.S.). Following a single-step protein precipitation of 500 microl samples with 250 microl acetone and 50 microl zinc sulfate 70% aqueous solution, the obtained supernatant was evaporated to dryness at 60 degrees C for exactly 45 min under a stream of nitrogen and the solid residue was solubilized in 200 microl of purified water. A 100 microl-volume was subjected to HPLC analysis onto a Nucleosil 100-5 microm C18 AB column equipped with a guard column (Nucleosil 100-5 microm C(6)H(5) (phenyl) end-capped) using a gradient elution of acetonitrile and 1-heptanesulfonic acid 0.2% pH 4: 15/85 at 0 min-->50/50 at 20 min-->100/0 at 22 min-->15/85 at 24 min-->15/85 at 26 min, delivered at 1 ml/min. The analytes were detected by fluorescence detection with excitation and emission wavelength set at 480 and 550 nm, respectively. The calibration curves were linear over the range of 2-1000 ng/ml for effluent and plasma matrices, and 0.1 microg/g-750 microg/g for tissues matrices. The method is precise with inter-day and intra-day relative standard deviation within 0.5 and 6.7% and accurate with inter-day and intra-day deviations between -5.4 and +7.7%. The in vitro stability in all matrices and in processed samples has been studied at -80 degrees C for 1 month, and at 4 degrees C for 48 h, respectively. During initial studies, heparin used as anticoagulant was found to profoundly influence the measurements of doxorubicin in effluents collected from animals under ILP. Moreover, the strong matrix effect observed with tissues samples indicate that it is mandatory to prepare doxorubicin calibration standard samples in biological matrices which would reflect at best the composition of samples to be analyzed. This method was successfully applied in animal studies for the analysis of effluent, serum and tissue samples collected from pigs and rats undergoing ILP.

Cardiac Function Assessed by Transesophageal Echocardiography During Pectus Excavatum Repair

BACKGROUND We assessed end-diastolic right ventricular (RV) dimensions and left ventricular (LV) ejection fraction by use of intraoperative transesophageal echocardiography before and after surgical correction of pectus excavatum in adults. METHODS A prospective study was conducted including 17 patients undergoing surgical correction of pectus excavatum according to the technique of Ravitch-Shamberger between 1999 and 2004. Intraoperative transesophageal echocardiography was performed under general anesthesia before and after surgery to assess end-diastolic RV dimensions and LV ejection fraction. The end-diastolic RV diameter and area were measured in four-chamber and RV inflow-outflow view, and the RV volume was calculated from these data. The LV was assessed by transgastric short-axis view, and its ejection fraction was calculated by use of the Teichholz formula. RESULTS The end-diastolic RV diameter, area, and volume all significantly increased after surgery (mean values +/- SD, respectively: 2.4 +/- 0.8 cm versus 3.0 +/- 0.9 cm, p < 0.001; 12.5 +/- 5.2 cm(2) versus 18.4 +/- 7.5 cm(2), p < 0.001; and 21.7 +/- 11.7 mL versus 40.8 +/- 23 mL, p < 0.001). The LV ejection fraction also significantly increased after surgery (58.4% +/- 15% versus 66.2% +/- 6%, p < 0.001). CONCLUSIONS Surgical correction of pectus excavatum according to Ravitch-Shamberger technique results in a significant increase in end-diastolic RV dimensions and a significantly increased LV ejection fraction.

Vacuum-Assisted Closure Device: A Useful Tool in the Management of Severe Intrathoracic Infections

BACKGROUND This study is an evaluation of the vacuum-assisted closure (VAC) therapy for the treatment of severe intrathoracic infections complicating lung resection, esophageal surgery, viscera perforation, or necrotizing pleuropulmonary infections. METHODS We reviewed the medical records of all patients treated by intrathoracic VAC therapy between January 2005 and December 2008. All patients underwent surgical debridement-decortication and control of the underlying cause of infection such as treatment of bronchus stump insufficiency, resection of necrotic lung, or closure of esophageal or intestinal leaks. Surgery was followed by intrathoracic VAC therapy until the infection was controlled. The VAC dressings were changed under general anesthesia and the chest wall was temporarily closed after each dressing change. All patients received systemic antibiotic therapy. RESULTS Twenty-seven patients (15 male, median age 64 years) underwent intrathoracic VAC dressings for the management of postresectional empyema (n=8) with and without bronchopleural fistula, necrotizing infections (n=7), and intrathoracic gastrointestinal leaks (n=12). The median length of VAC therapy was 22 days (range 5 to 66) and the median number of VAC changes per patient was 6 (range 2 to 16). In-hospital mortality was 19% (n=5) and was not related to VAC therapy or intrathoracic infection. Control of intrathoracic infection and closure of the chest cavity was achieved in all surviving patients. CONCLUSIONS Vacuum-assisted closure therapy is an efficient and safe adjunct to treat severe intrathoracic infections and may be a good alternative to the open window thoracostomy in selected patients. Long time intervals in between VAC changes and short course of therapy result in good patient acceptance.

Mortality, complications and loss of pulmonary function after pneumonectomy vs. sleeve lobectomy in patients younger and older than 70 years

Retrospective single institution analysis of all patients undergoing sleeve lobectomy or pneumonectomy between 2000 and 2005. Seventy-eight patients underwent pneumonectomy (65 patients <70 years, 13 patients >70 years) and 69 sleeve lobectomy (50 patients <70 years, 19 patients >70 years). Pre-existing co-morbidity, surgical indication and induction therapy was similarly distributed between treatment by age-groups. In patients <70 years, pneumonectomy and sleeve lobectomy resulted in a 30-day mortality of 3% vs. 0 and an overall complication rate of 26% vs. 44%, respectively. In patients >70 years, pneumonectomy and sleeve lobectomy resulted in a 30-day mortality of 15% vs. 0 and an overall complication rate of 23% vs. 32%. In both age groups, pneumonectomy was associated with more airway complications (NS) and a significantly higher postoperative loss of FEV(1) than sleeve lobectomy (P<0.0001, P<0.03). Age per se did not influence the loss of FEV(1) and DLCO for a given type of resection. Sleeve lobectomy may have a therapeutic advantage over pneumonectomy in the postoperative course of elderly patients.

Outcomes after transplantation of lungs preserved for more than 12 h: a retrospective study

BACKGROUND Ex-vivo lung perfusion (EVLP) can be used to extend overall lung preservation time by splitting one long cold ischaemic time into two shorter ones and interposing an additional EVLP time. We assessed the outcomes after clinical transplantation of lungs with more than 12 h of preservation time. METHODS For this retrospective study, we searched the Toronto Lung Transplant Program database for patients who had received at least one lung transplant between Jan 1, 2006, and April 30, 2015, at a single hospital in Toronto, Canada. We split the identified patients into those with a total preservation time of more than 12 h and those with a total preservation time of less than 12 h to act as the control group. Total preservation time was defined as the sum of first cold ischaemic time, EVLP time, and second cold ischaemic time. We excluded patients if they had received a heart-lung transplant or were younger than 18 years. In bilateral lung transplantations, we used the longer preservation time of the two lungs for analysis. Lung preservation was done according to present standards of care and EVLP was done according to the Toronto EVLP technique. The primary outcomes were survival and International Society for Heart and Lung Transplantation Primary Graft Dysfunction (PGD) grade at 72 h post-transplantation. We compared outcomes with our control group using univariable and multivariable models. FINDINGS We identified 906 patients who met eligibility criteria and had sufficient data for analysis (<12 h group [n=809]; mean lung preservation time 400·8 min [SD 121·8] vs >12 h group [n=97]; 875·7 min [109·0]). Median hospital and intensive-care unit length of stay were similar between the less than 12 h group and the more than 12 h group (hospital stay: 23 days [16-42] vs 25·5 days [17-50·25], p=0·60; intensive-care unit stay: 4 days [2-14] vs 4 days [2-16], p=0·53). PGD grade was also not different between the two groups at 72 h post-transplantation (p=0·85). There was also no difference in survival between the two groups as shown on Kaplan-Meier survival curves (p=0·61). Multivariable survival analysis using Coxs model showed increasing recipient age to be a significant variable affecting survival. INTERPRETATION Extension of graft preservation time beyond 12 h with EVLP does not negatively affect early lung transplantation outcomes. Extension of clinical lung preservation times might allow for more transplantations to be done as a result of improved facilitation and increased flexibility around timing of lung transplantation operations. FUNDING None.

Leukocyte–endothelial cell interaction is necessary for photodynamic therapy induced vascular permeabilization

Photodynamic therapy (PDT) affects vascular barrier function and thus increases vessel permeability. This phenomenon may be exploited to facilitate targeted drug delivery and may lead to a new clinical application of photodynamic therapy. Here, we investigate the role of leukocyte recruitment for PDT‐induced vascular permeabilization.