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Lung volume reduction surgery (LVRS) offers improvement in lung function, quality of life and even survival in well selected patients with severe emphysema. Patients with all types of emphysema morphology can profit from LVRS when certain selection criteria are present. Hyperinflation plays a key role in qualifying for the procedure. Candidate selection should be performed at high volume centers with a multidisciplinary emphysema board. Qualified thoracic surgeons together with pulmonologists and radiologists identify the suitable patient considering emphysema morphology with its target areas for resection, lung function parameters and cardiac comorbidities. This review outlines candidate selection, technique and results of LVRS to inform referring physicians how to screen und inform their patients.

Despite longstanding recognition of thymic epithelial neoplasms, there is no official American Joint Committee on Cancer/Union for International Cancer Control stage classification. This article summarizes proposals for classification of the T component of stage classification for use in the 8th edition of the tumor, node, metastasis classification for malignant tumors. This represents the output of the International Association for the Study of Lung Cancer and the International Thymic Malignancies Interest Group Staging and Prognostics Factor Committee, which assembled and analyzed a worldwide database of 10,808 patients with thymic malignancies from 105 sites. The committee proposes division of the T component into four categories, representing levels of invasion. T1 includes tumors localized to the thymus and anterior mediastinal fat, regardless of capsular invasion, up to and including infiltration through the mediastinal pleura. Invasion of the pericardium is designated as T2. T3 includes tumors with direct involvement of a group of mediastinal structures either singly or in combination: lung, brachiocephalic vein, superior vena cava, chest wall, and phrenic nerve. Invasion of more central structures constitutes T4: aorta and arch vessels, intrapericardial pulmonary artery, myocardium, trachea, and esophagus. Size did not emerge as a useful descriptor for stage classification. This classification of T categories, combined with a classification of N and M categories, provides a basis for a robust tumor, node, metastasis classification system for the 8th edition of American Joint Committee on Cancer/Union for International Cancer Control stage classification.

A previously well 24-year-old man complained of persistent epigastric pain after a session of intensive muscle building exercise especially of the abdominal muscles. The abdomen was diffusely tender without guarding. There was an increased concentration of bilirubin (64.7 mumol/l), GOT (117 U/l), GPT (529 U/l) and alkaline phosphatase (150 U/l). Ultrasound examination showed a widening of the choledochal duct to 11 mm without signs of gallstones. Endoscopic retrograde cholangiography additionally revealed contrast-medium extravasation from the left hepatic duct. Computed tomography, performed immediately afterwards, confirmed the extravasation, while liver and pancreas were unremarkable. Laparoscopy revealed a 5 mm tear in the left hepatic duct, close to the hepatic duct bifurcation with bile effusion into the peritoneal cavity. The latter was rinsed endoscopically with Ringer's solution and drains were placed in the omental bursa and subhepatically in the region of the bile leak. To relax the sphincter Oddi glycerol trinitrate was administered postoperatively, for the first five days 72 mg/24 h intravenously, then for nine days twice daily 20 mg by month. No more bile drained as early as the second postoperative day and the patient was free of symptoms 2 weeks later.

A universal and consistent stage classification system, which describes the anatomic extent of a cancer, provides a foundation for communication and collaboration. Thymic epithelial malignancies have seen little progress, in part because of the lack of an official system. The International Association for the Study of Lung Cancer and the International Thymic Malignancies Interest Group assembled a large retrospective database, a multispecialty international committee and carried out extensive analysis to develop proposals for the 8th edition of the stage classification manuals. This tumor, node, metastasis (TNM)-based system is applicable to all types of thymic epithelial malignancies. This article summarizes the proposed definitions of the T, N, and M components and describes how these are combined into stage groups. This represents a major step forward for thymic malignancies.

Introduction: The staging system for malignant pleural mesothelioma is controversial. To revise this system, the International Association for the Study of Lung Cancer Staging Committee developed an international database. This report analyzes prognostic variables in a surgical population, which are supplementary to previously published CORE variables (stage, histology, sex, age, and type of procedure). Methods: Supplementary prognostic variables were studied in three scenarios: (1) all data available, that is, patient pathologically staged and other CORE variables available (2) only clinical staging available along with CORE variables, and (3) only age, sex, histology, and laboratory parameters are known. Survival was analyzed by Kaplan-Meier, prognostic factors by log rank and stepwise Cox regression modeling after elimination of nonsignificant variables. p value less than 0.05 was significant. Results: A total of 2141 patients with best tumor, node, metastasis (TNM) stages (pathologic with/without clinical staging) had nonmissing age, sex, histology, and type of surgical procedure. Three prognostic models were defined. Scenario A (all parameters): best pathologic stage, histology, sex, age, type of surgery, adjuvant treatment, white blood cell count (WBC) (>= 15.5 or not), and platelets (>= 400 k or not) (n = 550). Scenario B (no surgical staging): clinical stage, histology, sex, age, type of surgery, adjuvant treatment, WBC, hemoglobin (

The lack of an official-stage classification system for thymic malignancies is an issue that hampers progress in this rare disease. A collaborative effort by the International Association for the Study of Lung Cancer and the International Thymic Malignancies Interest Group is underway to develop proposals for such a system. A database of more than 10,000 cases worldwide has been assembled to provide a solid basis for analysis. This report outlines the structure of the effort and the process that has been designed.

Die chirurgische Lungenvolumenreduktion (LVR) ist ein neuartiges operatives Behandlungskonzept für ausgewählte Patienten mit fortgeschrittenem Lungenemphysem, die trotz optimaler Therapie schon bei geringer Anstrengung an Atemnot leiden und funktionell erheblich eingeschränkt sind. Mittels beidseitiger videoassistierter thorakoskopischer Resektion werden die am meisten vom Emphysem betroffenen Lungenabschnitte reseziert. Dadurch wird die stark überblähte Lunge verkleinert und die Atemmechanik verbessert. Dieses Verfahren, das an spezialisierten Zentren eine überraschend geringe perioperative Mortalität und Morbidität hat, führt bei der Mehrheit der operierten Patienten zu einer deutlichen symptomatischen Verbesserung, die durch eine Besserung der Lungenfunktion und der körperlichen Belastbarkeit bedingt ist. Die maximale funktionelle Verbesserung wird innert drei Monaten nach der Operation erreicht und nimmt nach ein bis zwei Jahren langsam ab.

Introduction: Lobar lung transplantation is an option which provides the possibility to transplant an urgent listed recipient of small size with a size mismatched donor lung. We report our short and long term results with bilateral lobar lung transplantation with long term outcomes. Material and [for full text, please go to the a.m. URL], 130. Kongress der Deutschen Gesellschaft für Chirurgie

Die Inzidenz des malignen Pleuramesotheliom steigt weiterhin weltweit. Die Behandlung ist eine klinische Herausforderung, denn Patienten sterben ohne Behandlung in kurzer Zeit nach Diagnosestellung. Während der Nutzen der Chemotherapie bei fortgeschrittener Erkrankung etabliert ist, sind andere Aspekte der Behandlung noch immer umstritten, vor allem in Bezug auf das Resektionsausmaß bei einer Operation und die Anwendung einer Strahlentherapie. Aktuell werden die besten Überlebensraten von multimodalen Behandlungskonzepten berichtet, die eine Chemotherapie, Operation und allfällige Radiotherapie beinhaltet. Aber nicht alle Patienten profitieren von so einer Behandlung, weshalb aktuelle Bemühungen sich darauf konzentrieren, das Staging System zu verbessern. Ergebnisse translationaler Studien sollen verlässliche prädiktive und prognostische Marker hervorbringen. Trotz steigendem Wissen über die Tumorbiologie und der Tatsache, dass viele neue Stoffe verschiedene Stufen der Entwicklung erreicht haben, hat sich die Anzahl der neuen Behandlungen, welche für Patienten zugelassen wurden, nicht erhöht. Da das Mesotheliom eine seltene Erkrankung darstellt, ist die Patientenzahl in Studien limitiert. Hier stellen innovative Versuchsanordnungen (wie multi-arm multi-stage Versuche) unter Nutzung kooperativer Plattformen den besten Weg in die Zukunft dar, um weniger effektive Behandlungen zu eliminieren.

Ziel: Unsere 11-jährige Erfahrung am Universitätsspital Zürich mit Induktions-Chemotherapie und extrapleuraler Pneumonektomie (EPP) für das Maligne Pleuramesotheliom (MPM) zusammenzufassen. Methodik: Patienten mit histologisch bewiesenem MPM (alle Subtypen), eines Stadiums cT1-3[for full text, please go to the a.m. URL], Gemeinsame Jahrestagung der Deutschen, Österreichischen und Schweizer Gesellschaft für Thoraxchirurgie

Hintergrund: Prolongierte Luftfistelungen nach Lungenvolumenreduktions-Eingriffen (LVRS) für ein terminales Lungenemphysem werden in bis zu 50% der Fälle beschrieben und können mit ernsthaften Komplikationen im Zuge der verlängerten Immobilisierung assoziiert sein. Das Ziel [for full text, please go to the a.m. URL], 16. Jahrestagung der Deutschen Gesellschaft für Thoraxchirurgie

Hintergrund: Respiratorisch schwer eingeschränkte Patienten wegen COPD und Emphysem vom heterogenen Typ weisen nach LVRS sowohl klinisch als auch funktionell eine erhebliche Besserung auf. Patienten mit nicht-heterogenem Emphysem profitieren möglicherweise ebenfalls von einer LVRS sofern eine[for full text, please go to the a.m. URL], 16. Jahrestagung der Deutschen Gesellschaft für Thoraxchirurgie

Hintergrund: Auch nach aggressiven multimodalen Behandlungsansätzen, ist das Lokalrezidiv nach wie vor ein grosses Probelm in der Behandlung von Mesotheliompatienten. Die intrakavitäre Behandlung hat den Vorteil, das jeweilige Therapeutikum hochkonzentriert vor Ort einzubringen. Ziel: [for full text, please go to the a.m. URL], Gemeinsame Jahrestagung der Deutschen, Österreichischen und Schweizer Gesellschaft für Thoraxchirurgie

Hintergrund: Das Postpneumonektomie-Empyem (PPE) ist eine seltene aber schwerwiegende Komplikation. Die erfolgreiche Behandlung ist auch für den erfahrenen Thoraxchirurgen eine Herausforderung. Vor 5 Jahren haben wir erstmals unser beschleunigtes Therapie-Verfahren international vorgestellt. In[for full text, please go to the a.m. URL], 16. Jahrestagung der Deutschen Gesellschaft für Thoraxchirurgie

Hintergrund: Die thorakoskopische Resektion von mediastinalen Tumoren ist machbar, die Indikationen sind aber aufgrund der limitierten Beweglichkeit der Instrumente und der zwei-dimensionale Sicht beschränkt. Wir haben den Einsatz des Da Vinci® Telemanipulators für Resektionen von unterschiedlichen[for full text, please go to the a.m. URL], 16. Jahrestagung der Deutschen Gesellschaft für Thoraxchirurgie

Hintergrund: Die Mortalität von Pneumonektomie nach Chemotherapie oder Chemoradiotherapie für lokal fortgeschrittenen nicht-kleinzelliges Lungenkarzinom beträgt bis zu 26%. Wir analysierten die Akten von entsprechenden Patienten nach einem solchen Eingriff, welcher in 2 verschiedenen[for full text, please go to the a.m. URL], Gemeinsame Jahrestagung der Deutschen, Österreichischen und Schweizer Gesellschaft für Thoraxchirurgie

Background: In patients with a centrally located broncho-pulmonary lesion, sleeve resection is the operation of choice in order to avoid a pneumonectomy. Most centers wrap the bronchial anastomoses with viable tissue to protect them from insufficiencies. In this study we report our single center experience[for full text, please go to the a.m. URL], Gemeinsame Jahrestagung der Deutschen, Österreichischen und Schweizer Gesellschaft für Thoraxchirurgie

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 distress.

In an ongoing prospective study 11 patients with unresectable liver metastases from colorectal carcinoma have been treated with hepatic-arterial infusion of 5-FU (1 g m-2) for 24 h on days 1 to 5 combined with a rapid infusion of high-dose leucovorin (100 mg m-2) (HD-regimen) or low-dose leucovorin (20 mg m-2) (LD-regimen) on days 1, 3 and 5. There was only mild local toxicity grade 1 and grade 2 in both regimen. Twenty-four cycles with high-dose leucovorin and 42 cycles with low-dose leucovorin showed a mild to moderate systemic toxicity, including haematological changes, stomatitis and diarrhoea. We did not see any grade 4 toxicity and no treatment-related fatalities occurred in this series. Eighty per cent reduction of leucovorin dosage leads to a significant decrease in grade 2 and grade 3 haematological and gastrointestinal toxicity.

Between 1970 and 1975 166 iridectomies were performed in cases of primary glaucoma. In the retrospective study reported here the authors analyzed the results with regard to the regulation of intraocular pressure (IOP) and loss of function. Follow-up examinations were performed (1) between 6 weeks and 6 months, (2) 12 months, (3) 1.5 to 2.5 years and (4) 3 to 4 years after surgery in patients whose IOP was not adequately regulated. Hypotonia was rare. Of the eyes with acute narrow-angle glaucoma with an open iridocorneal angle by definition, which underwent surgery for the first time, 30% had an IOP of more than 21 mm Hg with or without additional tension-lowering medication (20% between 22 and 24 mm Hg, 10% over 24 mm Hg). The results for eyes operated on for the second time were better because of the prophylactic iridectomies in this group. In one-third of the cases the iridocorneal angle was occluded; in two-thirds an open angle was found. An analysis revealed that regulation was better when the previous tension level had been high, while lower tension levels, of between 20 and 35 mm Hg, often remained elevated after surgery. Out of the total number of eyes operated on for the first time (narrow-angle and open-angle glaucoma) IOP was regulated by iridectomy alone in 54% after 1 year and in 33% after 2 years. With regard to the iridocorneal angle of these 33%, it was found that 50% of the cases of narrow-angle glaucoma were regulated without further medication, but only 20% of the open-angle cases.(ABSTRACT TRUNCATED AT 250 WORDS)

The two most important methods used for objective determination of visual acuity are those of Ohm-von Romberg and Gunther. A newly developed instrument based on Gunther's principle is described which combines the advantages of both methods. Using a Leitz projector and a specially designed accessory unit, a constantly moving screen of dots measuring 64 X 64 cm is projected. The setting was standardized on the basis of 358 eyes with visual acuities ranging from finger counting to 1.0. The correlation between the measured distance (from screen to patient) at which an optokinetic nystagmus was just induced and visual acuity was r = 0.98 over the entire visual acuity range. The visual acuity to be expected can be read off from the diagrams or a table, with a scatter range of +/- 1 sigma, +/- 2 sigma, or +/- 3 sigma. The relevant literature is discussed. Replication of the accessory unit described can be recommended.

Changes in certain areas of the fundus are frequently accompanied by changes in the spectral distribution of the reflected light. In many diseases of the fundus, it is desirable to have an objective definition of the color of the fundus during a particular phase of the disease. An instrument designed by Carl Zeiss, Oberkochen, West Germany, provides a satisfactory solution to the problem of measuring color on the fundus. Transformational equations make it possible to convert the measurement parameters obtained by visual comparison into standardized color measurement values. The measurement error is slighter than necessary for clinical examinations. Incipient cataracts cause only a slight shift of the color co-ordinates.

Introduction:Thymic carcinoma is a rare and aggressive thymic neoplasm. The European Society of Thoracic Surgeons developed a retrospective database collecting patients undergoing resection for thymic tumors from 1990 to 2010.Methods:Of 2265 patients with thymic tumors, there were 229 thymic carcinomas. Clinicopathological characteristics were analyzed including age, associated paraneoplastic diseases, stage (Masaoka-Koga), World Health Organization histologic subtypes, type of resection (total/subtotal/biopsy/no resection), tumor size, pre/postoperative treatments, and recurrence. Outcome measures included overall survival (OS), freedom from recurrence, and cumulative incidence of recurrence.Results:A complete resection was achieved in 140 patients (69%). Recurrence occurred in 54 patients (28%). Five- and 10-year OS rates were 0.61 and 0.37. Five- and 10-year freedom from recurrence rates were 0.60 and 0.43. Cumulative incidence of recurrence was 0.21 (3 yr), 0.27 (5 yr), and 0.32 (10 yr). Survival was better after surgical resection versus biopsy/no resection (p < 0.001), after complete resection versus subtotal resection (p < 0.001), and when using Masaoka-Koga system (stages I–II versus III versus IV) (p < 0.001). The use of multidisciplinary treatments resulted in a survival advantage which was significant in the surgery + radiotherapy group (p = 0.02). Incomplete resection (p < 0.0001) and advanced stage (Masaoka-Koga III–IV) (p = 0.02) had a negative impact on OS at multivariable analysis. Administration of adjuvant radiotherapy was beneficial in increasing OS (p = 0.02).Conclusions:The results of our study indicate that patients with thymic carcinoma should undertake surgical resection whenever possible; a complete resection and early Masaoka-Koga stage are independent predictors of improved survival; our results also suggest that postoperative radiotherapy is beneficial in improving survival.

OBJECTIVES Lung volume reduction surgery (LVRS) improves dyspnoea, quality of life and may even prolong survival in carefully selected patients with end-stage emphysema. The benefit may be sustained for several years and vanishes with the natural progression of the disease. Data on repeated surgical treatment of emphysema are scarce. The aim of this study was to evaluate the safety, effects and outcomes of repeated LVRS (Re-LVRS) in patients no longer benefiting from their initial LVRS. METHODS Between June 2002 and December 2013, 22 patients (9 females) with advanced emphysema underwent Re-LVRS at a median of 60 months (25–196) after their initial LVRS. While initial LVRS was performed thoracoscopically as a bilateral procedure, Re-LVRS was performed unilaterally by a video-assisted thoracoscopic technique in 19 patients and, due to adhesions, by thoracotomy in 3 patients. Pulmonary function test (PFT) was performed at 3 and 12 months postoperatively. RESULTS Lung function at Re-LVRS was similar to that prior to the first LVRS. The 90-day mortality rate was 0%. The first patient died 15 months postoperatively. The median hospitalization time after Re-LVRS was significantly longer compared with the initial LVRS [14 days, interquartile range (IQR): 11–19, vs 9 days, IQR: 8–14; P = 0.017]. The most frequent complication was prolonged air leak with a median drainage time of 11 days (IQR: 6–13); reoperations due to persistent air leak were necessary in 7 patients (32%). Five patients (23%) had no complications. Lung function and Medical Research Council (MRC) score improved significantly for up to 12 months after Re-LVRS, with results similar to those after initial bilateral LVRS. The average increase in the forced expiratory volume in 1 s (FEV1) was 25% (a 7% increase over the predicted value or 0.18 l) at 3 months, and the mean reduction in hyperinflation, assessed by relative decrease in RV/TLC (residual volume/total lung capacity), was 12% at 3 months (a decrease of 8% in absolute ratios). The mean MRC breathlessness score decreased significantly after 3 months (from 3.7 to 2.2). CONCLUSIONS Re-LVRS can be performed successfully in carefully selected patients as a palliative treatment. It may be performed as a bridge to transplantation or in patients with newly diagnosed intrapulmonary nodules or during elective cardiac surgery. Morbidity is acceptable and outcomes may be satisfactory with significantly improved lung function and reduced dyspnoea for at least 12 months postoperatively.

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 1 ), 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 1 , containing 0.7 mg sildenafil/l was used, and the graft stored at 1 8C 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 reperfusionperiod;in contrast,all control animalsdied within1—2 h after occlusionof the rightside. In comparison to a markedrise inpulmonary 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, allowinglung 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 improved.

To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines of treatment in advanced disease, early-stage disease and locally advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on first line/second and further lines of treatment in advanced disease.

In a number of large case series in the mid-1990s, lung volume reduction surgery (LVRS) was shown to reduce dyspnoea and improve pulmonary function and quality of life in patients with advanced pulmonary emphysema. The large randomised National Emphysema Treatment Trial (NETT) confirmed this in the early 2000s and also demonstrated that selected patients live longer after surgery. Patient selection is crucial to the success of the procedure and should be performed at a specialised experienced centre with a multidisciplinary team approach on emphysema treatment. The upper-lobe predominant heterogeneous type of emphysema is the best indication, but there are other types of emphysema morphology that are also eligible for surgery, if ideally chosen. Nowadays there is also growing evidence for positive effects after different types of bronchoscopic lung volume reduction (BLVR) with increasing quality. These methods add to the range of multimodal emphysema treatment.

To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines of treatment in advanced disease, early-stage disease and locally advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on locally advanced disease.

Objective: To investigate the incidence and management of postoperative complications after neoadjuvant chemotherapy followed by extrapleural pneumonectomy for malignant pleural mesothelioma. Methods: Patients with histologically proven mesothelioma of clinical stages T1—3, N0—2, M0 and considered to be completely resectable received neoadjuvant chemotherapy (cisplatin + gemcitabine or cisplatin + pemetrexed) followed by extrapleural pneumonectomy and postoperative radiotherapy. The incidence and management of postoperative complications in general and of bronchopleural fistula and postpneumonectomy-empyema in particular were analyzed. Univariate analysis was performed toidentifyprognosticfactors[sex,age,sideofoperation,weightloss,smoking,chemotherapy, EORTC-score(EuropeanOrganizationforResearch and Treatment of Cancer-classification) and duration of operation]. Results: Between 1st May 1999 and 15th August 2005, 63 patients underwent complete extrapleural pneumonectomy after neoadjuvant chemotherapy. Postoperative complications were observed in 39 cases (62%) and 2 patients died within 30 days (3.2%). Postpneumonectomy-empyema occurred in 15.8% of the patients (n = 10), six with a bronchopleuralfistula on the right side. All empyemas were treated successfully. Five patients developed chylothorax (7.9%) and four patients had complications due to a patch failure: cardiac herniation (n = 2), restriction of cardiac output (n = 1) or gastric herniation (n = 1). Patients with higher EORTC-score presentedsignificantly morepostoperativecomplications (p = 0.03). A longer duration of surgery tended to be associatedwith a higher incidence of postoperative complications, especially of empyemas. Conclusions: Extrapleural pneumonectomy after neoadjuvant chemotherapy can be performed with mortality rates comparable to standard pneumonectomies. Complications are frequent but can be successfully managed; the EORTC-score seems to be a predictor for postoperative complications.

Objective: Among the many immunosuppressive effects of SDZ RAD (40-0(2-hydroxyethyl)-rapamycin), a rapamycin derivative, is the inhibition of fibroblast proliferation. Since the long-term success of lung transplantation is limited by the development of bronchiolitis obliterans, a fibroblast-associated progressive luminal obstruction of the terminal bronchioli, the use of SDZ RAD as immunosuppressive in pulmonary graft recipients may counteract this process. However, reduction of fibroblast activity, posttransplant, may impair the healing of the bronchial anastomoses. Materials and methods: The cervical trachea in pigs was denuded, divided and re-anastomosed with Prolene 4-0 single stitches. Control animals (group 1, n ¼ 4) were without, and study animals (group 2, n ¼ 6) were with SDZ RAD therapy (1.25 mg/kg/day, p.o., 14 days). After 14 days, the pigs were sacrificed. The anastomoses were examined histologically, and breaking strength of tracheal strips of 5-mm width was measured. Results: All animals survived without complications. Serum levels of SDZ RAD were 30.9 ^ 8.7 ng/ml (recommended level 20‐ 40 ng/ml). All anastomoses healed macroscopically without difference between the two groups. Breaking strength was significantly lower in the treated animals (group 1 vs. group 2: 11.75 ^ 0.35 vs. 7.69 ^ 1.39 N, P ¼ 0:01). Histology did not show a significant change in histoarchitecture between the groups. Conclusions: Although SDZ RAD significantly reduced the breaking strength of the tracheal anastomosis, no obvious histological differences between treated and untreated animals could be detected. Since this model does not reflect the clinical situation, further investigations are necessary to reveal the effect of SDZ RAD on airway wound healing in concert with a contemporary clinically used multidrug immunosuppressive regimen in allograft recipients. q 2003 Elsevier Science B.V. All rights reserved.

The different modalities in the treatment of tuberculosis (TB) changed within the last century. With the beginning of the era of effective antibiotic treatment, indication for surgical methods became rare. The combination of different classes of antibiotics to treat TB is most often effective but several multi-drug-resistant germs were created, leading to the need of surgical resection as adjuvant treatment. The aim of this review is to summarize the current role of surgical therapy in treating TB. Zusammenfassung: Seit Ende des letzten Weltkriegs hat sich die Therapie der Tuberkulose durch den Einsatz der verschiedenen Antibiotika masgeblich verandert. Die Tuberkulose ist zu einer in der Regel medikamentos heilbaren Erkrankung geworden. Durch zum Teil unsachgemasen Einsatz von Einzelsubstanzen ist es zum Auftreten von Resistenzen gegen die antibiotische Therapie gekommen. Die chirurgische Resektion zerstorter, oft kavernos veranderter Lungenanteile hat einen definierten Stellenwert als adjuvante Therapie in der Behandlung der Tuberkulose, meist der multiresistenten Tuberkulose.

ObjectiveOur objective was to evaluate whether platinum concentrations in chest wall tissue and in serum are optimized by intracavitary application of cisplatin loaded to a fibrin carrier compared with cisplatin solution in a randomized setting of a pig model.MethodsAfter left-sided pneumonectomy including parietal pleurectomy, pigs were randomly assigned to receive either 90 mg/m2 cisplatin intracavitary solution (n = 6) or to receive 5 mg cisplatin-fibrin (n = 5) applied on a predefined area of the chest wall. Platinum concentration in serum as well as in chest wall tissue was determined at several early time points until day 5 after treatment. Platinum levels were measured by inductively coupled plasma sector field mass spectrometric detection with a matrix-matched calibration procedure.ResultsThe dose- and surface-corrected (geometric) mean concentration of cisplatin in chest wall tissue 2 hours but also at day 5 after the application was doubled in animals treated with cisplatin-fibrin compared with the animals treated with cisplatin-solution. In serum, the dose- and surface-corrected exposure toward cisplatin (area under the curve0-5d) was significantly lower with cisplatin-fibrin than with cisplatin-solution (P

The purpose of our study was to assess robustness of volumetric measurement of malignant pleural mesothelioma (MPM) before and after chemotherapy to modified RECIST (response evaluation criteria in solid tumours) criteria. 30 patients with digitally available chest computed tomography (CT) scans before and after three cycles of chemotherapy were included. Three readers independently assessed tumour response using two different methods: 1) the modified RECIST criteria; and 2) the tumour volumetric approach using dedicated software (Myrian®; Intrasense, Paris, France). Inter-rater reliability of unidimensional and volumetric measurements was assessed using intraclass correlation. Tumour response classification for modified RECIST was compared to the volumetric approach applying unidimensional RECIST volumetric equivalent criteria. The determination of unidimensional tumour measurement (RECIST) revealed a low inter-rater reliability (0.55) and a low interobserver agreement for tumour response classification (general κ 0.33). Only 14 patients were classified equally. A high inter-rater reliability (0.99) and interobserver agreement (general κ 0.9) were found for absolute tumour volumes (volumetric measurements). 27 cases were classified equally. The number of cases classified as “stable disease” was higher for the volumetric approach using tumour-equivalent criteria compared to modified RECIST. Volumetric measurement of MPM on CT using Myrian® software is a reliable, reproducible and sensitive method to measure tumour volume and, thus, therapy response after induction chemotherapy.

PURPOSE OF REVIEW: The major cause of death following lung transplantation in the beginning after the first human lung transplantation in 1963 was airway dehiscence, representing a major obstacle to widespread use of this treatment option. Lung transplantation is unique among all solid organ transplantations, since systemic arterial blood supply is not restored during engraftment. In the eighties and thereafter the problem of airway healing after lung transplantation was the main focus of research. This review focuses on the incidence of airway anastomotic complications after lung transplantation and delineates potential risk factors. RECENT FINDINGS: Refinements in lung preservation and surgical technique have reduced the incidence of airway complications. Reflecting these changes, the contemporary rate of anastomotic lesions following lung transplantation has dropped from 80% before 1983 to less than 3% with a range of 2.6-23.8%. Small clinical series of lung transplantation with direct bronchial artery revascularization have reported promising early results. However, direct bronchial artery revascularization has been considered a difficult and unreliable method to be used clinically, as it prolongs the operation and ischemic time, increases risk of bleeding, and because of the good results reported from transplants without bronchial artery revascularization. At the present time (nearly) all transplant centers perform the airway anastomosis without bronchial artery revascularization. SUMMARY: Bronchial anastomotic complications can be avoided by use of a standardized surgical technique which respects the fact that the donor bronchus is poorly vascularized. Prevention of fungal infections with aggressive antifungal treatment may play an important additive role.

Objective The mortality of pneumonectomy after chemotherapy or chemoradiotherapy for locally advanced non–small-cell lung cancer is reported to be as high as 26%. We retrospectively reviewed the medical records of patients undergoing these procedures in 2 specialized thoracic centers to determine the outcome. Methods Retrospective analyses were performed of all patients who underwent pneumonectomy after neoadjuvant chemotherapy or chemoradiotherapy for locally advanced non–small-cell lung cancer from 1998 to 2007. Presurgical treatment consisted of 3-4 platin-based doublets alone in 20% of patients or combined with radiotherapy (45Gy) to the tumor and mediastinum in 80% of patients. Results Of 827 patients who underwent neoadjuvant therapy, 176 pneumonectomies were performed, including 138 (78%) extended resections. Post-induction pathologic stages were 0 in 36 patients (21%), I in 33 patients (19%), II in 38 patients (21%), III in 57 patients (32%), and IV in 12 patients (7%). Three patients died of pulmonary embolism, 2 patients of respiratory failure, and 1 patient of cardiac failure, resulting in a 90 postoperative day mortality rate of 3%; 23 major complications occurred in 22 patients (13%). For the overall population, 3-year survival was 43% and 5-year survival was 38%. Conclusion Pneumonectomy after neoadjuvant therapy for non–small-cell lung cancer can be performed with a perioperative mortality rate of 3%. Thus, the need of a pneumonectomy for complete resection alone should not be a reason to exclude patients from a potentially curative procedure if done in an experienced center. The 5-year survival of 38%, which can be achieved, justifies extended surgery within a multimodality concept for selected patients with locally advanced non–small-cell lung cancer.

Over the last decade, several improvements have been made in the diagnosis and treatment of malignant pleural mesothelioma, including better understanding of tumor biology, availability of more potent chemotherapeutic drugs, improved surgical management, and optimized multidisciplinary therapy. Radical tumor resection by means of extrapleural pneumonectomy (EPP) is now feasible with acceptable morbidity and mortality, even after neoadjuvant chemotherapy, if performed in specialized centers. To date, the best survival data have been reported after multimodality treatment strategies that include surgical resection. In this article, we discuss several strategies that involve EPP or pleurectomy/decortication in combination with various adjuvant and neoadjuvant therapies.

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 role.

OBJECTIVE: To assess the effect of immuno-chemotherapy on the extent of local tumour recurrence in an established rat model of malignant pleural mesothelioma (MPM). METHODS: Six days after subpleural inoculation of a syngeneic MPM cell line Interleukin-45 (IL-45), left-sided pneumonectomy and resection of the tumour nodule was performed. Animals were randomised into four treatment groups for intrapleural therapy: control (n=6), 500 microg cytosine phosphate guanosine oligodeoxynucleotide (CpG-ODN) (n=6), cisplatin-fibrin (n=6), cisplatin-fibrin+500 microg CpG (n=6). Six days later the volume of tumour recurrence was assessed, which was the primary endpoint. Secondary endpoints were quantification of the ratio host/tumour cells in the local recurrence and cytokine expression profile in the tumour tissue by real time quantitative PCR (qPCR). T lymphocyte subpopulations in the tumour recurrence tissue were evaluated by immunohistochemistry. Treatment-related toxicity was monitored by measuring blood chemistry and complete blood count. RESULTS: The volume of tumour recurrence was significantly reduced from 610 mm(3) in the control group to 11.7 mm(3) in the cisplatin-fibrin group (p=0.004) and to 21.8mm(3) in the cisplatin-fibrin+CpG group (p=0.004). Pro-inflammatory cytokines (Interferon-gamma (IFN-gamma), Interleukin-6 (IL-6), Interleukin-12 (IL-12)) were increased after treatment with cisplatin-fibrin+CpG in comparison to cisplatin-fibrin alone but differences were not statistically significant. We found a higher ratio of host/tumour cells in the cisplatin-fibrin+CpG group (45/55%) compared to the cisplatin-fibrin group (27/73%). In comparison to the control group, animals treated with cisplatin-fibrin+CpG showed a higher number of CD8+ T-cells in the tumour tissue. No significant treatment-related toxicity was observed. CONCLUSIONS: Adjuvant treatment with chemotherapy or immuno-chemotherapy leads to significant reduction of mesothelioma recurrence after surg in this rat MPM model. Immuno-chemotherapy resulted in an increased recruitment of inflammatory cells to the site of tumourigenesis and elicited higher level of tumour growth inhibiting cytokines.

Patients with a homogeneous type of emphysema have been excluded a priori from LVRS in many centers because of the fear of removing parenchyma, which potentially contributes to gas exchange, and because the observation that heterogeneity of emphysema is a predictor of functional improvement. It is obvious that resection of functionless tissue, such as in heterogeneous emphysema with bullae, can be advised to the patient with a relative low risk. However, as the main positive effect of LVRS is its improvement on respiratory mechanics, it is not surprising that well-selected patients with homogeneous emphysema also benefit from surgery. Their selection has to be done cautiously. It is crucial to exclude patients with a very low functional reserve, such as with diffusing capacity below 20% predicted or with pulmonary hypertension, and with extreme parenchymal loss (vanished lungs) on CT from LVRS. Additionally, cofactors which may potentially interfere with a smooth postoperative course, such as previous recurrent infections, extensive scarring of the lungs, or previous surgery, have to be taken into consideration. When respecting these caveats, LVRS in patients with complete homogeneous emphysema provides a comparable symptomatic and almost the same functional improvement as in patients with heterogeneous emphysema. Although the perioperative mortality is low, patients with homogeneous emphysema have a slightly reduced long-term survival without lung transplantation compared with patients with heterogeneous emphysema. Based on our own experience, we conclude that LVRS can be recommended to selected symptomatic patients with advanced homogenous emphysema associated with severe hyperinflation, if diffusing capacity is not below 20% of predicted values and if the CT scan does not show aspects of vanished lungs.

The purpose of this study was to evaluate whether favorable short-term results achieved by lung volume reduction surgery in selected patients with homogeneous emphysema would persist for longer periods. Their symptoms, lung function, and survival for several years were analyzed in comparison to patients with heterogeneous emphysema.Two hundred fifty consecutive patients (105 women), mean (+/- standard deviation) age 64 +/- 8.4 years, with advanced emphysema underwent bilateral thoracoscopic lung volume reduction surgery. Forced expiratory volume in 1 second was 28% +/- 8% of predicted, 6-minute walking distance was 245 +/- 118 m, and Medical Research Council dyspnea score was 3.5 +/- 0.7. In 138 patients (55%) computed tomography revealed homogeneous emphysema (including 82 intermediate type) distribution and in 112 patients (45%) heterogeneous emphysema. Baseline characteristics were otherwise similar in the two groups that were prospectively observed for several years.Thirty-day mortality was 2.4%. Both groups revealed significant improvements 3 months after lung volume reduction surgery: in homogeneous emphysema, predicted forced expiratory volume in 1 second was 38% +/- 14% (35% improvement), 6-minute walk distance was 324 +/- 87 m, and dyspnea score was 1.8 +/- 0.9 (p0.05 all outcomes). Corresponding results in heterogeneous emphysema were 44% +/- 15% (61% improvement), 382 +/- 95 m, and 1.3 +/- 0.9 points (p0.05 versus baseline; not significant versus homogeneous). Median time until predicted forced expiratory volume in 1 second and 6-minute walk distance had returned to baseline was 36 months in both groups. One-year survival was similar in both groups. At 5 years, median survival without lung transplantation was 64% in the homogeneous and 73% in the heterogeneous group (Cox proportional hazard, 0.81; 95% confidence interval, 0.66 to 0.98; p = 0.03).In selected patients with homogeneous pulmonary emphysema, lung volume reduction surgery can be successfully performed with low perioperative mortality. Significant improvements in dyspnea, lung function, and exercise capacity are maintained for several years.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a highly aggressive tumour with poor prognosis and limited response to therapy. MPM is characterised by complex chromosomal aberrations, including chromosome 10 losses. The tumour suppressor gene phosphatase and tensin homologue deleted from chromosome 10 (PTEN) located on chromosome 10q23 plays an important role in different cancer, but its relevance for MPM is unclear. PATIENTS AND METHODS: In the present tissue microarray-based study, 341 MPM were studied for PTEN expression by immunohistochemistry using a monoclonal mouse PTEN antibody. Expression levels were semiquantitatively scored (negative, weak, moderate, strong). Expression of PTEN was correlated to overall survival. RESULTS: Clinical data from 206 patients were available. One hundred and five patients were stage T4 and 92 patients presented with regional and mediastinal lymph node metastasis. Loss of PTEN expression was observed in 62% of the cases. The survival time was correlated to PTEN expression in 126 cases with complete follow-up data. Comparing any PTEN expression versus no expression, median survival time was significantly longer (log rank test p=0.0001) in patients with PTEN expression (15.5 months; 95% CI: 3.8; 27.2 vs 9.7 months; 95% CI: 7.9; 11.7). Cox regression analysis revealed an association between PTEN expression and survival (p=0.003) independently from the histological subtype (p=0.7). CONCLUSION: PTEN is an independent prognostic biomarker in mesothelioma patients. The frequent loss of expression of the tumour suppressor gene PTEN suggests involvement of the PI3K-AKT/protein kinase B (PKB) pathway in MPMs, which may be relevant for future mesothelioma treatment.

OBJECTIVE: Postpneumonectomy empyema remains a clinical challenge. We proposed an accelerated therapy without an open chest window 5 years ago. This concept was evaluated on a larger scale in 2 centers in 2 different countries. METHODS: Between July 1995 and October 2005, 75 consecutive patients with postpneumonectomy empyema were treated in Szczecin, Poland (n = 35), and Zurich, Switzerland (n = 40). The therapy consisted of repeated open surgical debridement of the pleural cavity after achievement of general anesthesia, a negative pressure wound therapy of the temporarily closed chest cavity filled with povidone-iodine-soaked towels, and continuous suction and systemic antimicrobial therapy. If present, bronchopleural fistulae were closed and reinforced either with a muscle flap or the omentum. Finally, the pleural space was filled with an antibiotic solution and definitively closed. RESULTS: Of 75 patients (63 men; median age, 59 years; age range, 19-82 years), postpneumonectomy empyema was present on the right in 46 patients (32 with bronchopleural fistula) and in 29 patients (12 with bronchopleural fistula) on the left. Median time between pneumonectomy and postpneumonectomy empyema was 131 days (range, 7-7200 days). Bronchopleural fistulae have been closed and additionally reinforced by means of different methods (omentum, 18; muscle, 11; pericardial fat, 5; azygos vein, 1). The chest was definitively closed within 8 days in 94.6% of patients. The median hospitalization time was 18 days (range, 9-134 days). Postpneumonectomy empyema was successfully treated in 97.3% of patients, including 10 (13%) patients who needed a second treatment cycle. Three (4%) patients died within 90 days. The median follow-up time was 29.5 moths (range, 3-107 months). CONCLUSIONS: Treatment of postpneumonectomy empyema with the accelerated treatment is effective and safe. Our results are superior compared with those in reported series using a (temporary) chest fenestration. Patients appreciate the physical integrity of the chest.

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 (!250 mmHg) 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 O55 years, smoking O20 pack-years, PaO2 before harvesting !300 mmHg, 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 6month 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), PZ0.32), mean duration of mechanical ventilation (d) (4.4G2.7 (I) vs. 2.6G2.1 (II), PZ0.2), mean length of stay at the ICU (d) (11.5G8.8 (I) vs. 9.2G6.9 (II), PZ0.4), 6-month pulmonary function (FEV1Z83G23% of the predicted value (I) vs. 82G18% (II), PZ 0.81), 30-day survival (90.6% (I) vs. 93.7% (II), PZ0.56), 1-year survival (83.5% (I) vs. 81% (II), PZ0.83). Thirty-day survival was also comparable even in recipients from donor lungs with PaO2!250 mmHg (nZ8) (90.6% (I) vs. 87.5%, PZ0.57). The number of extended criteria had no impact on the outcome. The combination of PaO2!300 mmHg 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 !250 mmHg before harvesting of the lungs is not an absolute contra-indication for transplantation.

OBJECTIVE: Phosphodiesterases (PDEs) negatively regulate the concentrations of cAMP and/or cGMP, which act as downstream second messengers to the prostaglandins. PDE type-4 (PDE4) is selective for cAMP and is found in high concentrations in endothelial, epithelial, and different blood cells. The aim of this study was to evaluate if PDI747, a novel selective inhibitor of PDE4, can restore pretransplant cAMP levels and thereby posttransplant organ function after prolonged cold ischemia. METHODS: Left lung transplantation was performed in pigs (25-31 kg). Donor lungs were flushed with low potassium dextran glucose (LPDG) solution only (control, n=5)or, in addition with 1 micromol of PDI747 (PDI747, n=5) and stored for 30 h at 1 degrees C. PDI747 animals further received a bolus of PDI747 (0.3 mg/kg) 15 min prior to reperfusion and a continuous infusion (0.3 mg/kg per hour) during the 5 h after reperfusion. After occlusion of the right pulmonary arteries and the right main bronchus, hemodynamic and gas exchange parameters and extravascular lung water (EVLW) levels of the transplanted lung were assessed. RESULTS: Two control animals died of severe lung edema leading to heart failure (control, n=3). One animal in the treatment group was excluded due to a patent ductus arteriosus (PDI747, n=4). Gas exchange at the end of the experiment was restored to normal levels in the PDI747 group (Pa, O(2) 47.6+/-11.2 kPa, Pa,CO(2) 6.4+/-1.8 kPa) but not in the control group (Pa, O(2) 7.7+/-2.9 kPa, Pa, CO(2) 11.9+/-3.0 kPa, P(PaO2)

Objective: To date numerous attempts have been undertaken to conquer the challenging problem of reconstructing long segmental tracheal defects, as yet without lasting success. Recently, employing concepts of tissue engineering in animals, cartilage-like constructs were transplanted in vivo. However, both the feasibility of fabricating tracheal replacements and the use of human tracheal chondrocytes (HTC) for tissue engineering are still under investigation. In this study we optimized isolation and cultivation techniques for human tracheal cartilage, assessing the feasibility of seeding these cells onto a novel, three-dimensional (3-D) polyester-urethane polymer (DegraPol®). Methods: Human tracheal cartilage was harvested from the trachea of lung donors, digested in 0.3% collagenase II, and the condrocytes serially passaged every 7-9) days. Cells were also cultivated over agar plate during the total 6-8 weeks expansion phase. Thereafter, chondrocytes were seeded onto DegraPol® (pore sizes 150-200 μm) with a seeding density of 2.4 × 10 7 /ml, and chondrocyte-polymer constructs maintained during in vitro static culture. Results: HTC displayed stable proliferation kinetics in monolayer culture with positive expression of collagen type II. Following polymer seeding, both cellular proliferation and extracellular matrix (ECM) production, as measured by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and glycosaminoglyucan assays, continued over extended culture. Active growth of HTC on DegraPol® was further demonstrated by Alcian blue staining, with the histomorphological appearance of the construct resembling that of native cartilage. Scanning electron microscopy showed chondrocyte growth and ECM synthesis both on the surface and inside the porous scaffold, with a dense cell layer on the surface of the scaffold and a lower cell distribution in the scaffold's interior. Conclusions: The harvested chondrocytes from human trachea cartilage expand well in vitro and possess the ability to form new cartilage-like tissue when seeded onto DegraPol® matrix. However, improved culture conditions are needed to permit cellular growth throughout cell-polymer constructs.

Thank you for your comments regarding the article on `Early and long term complaints following video-assisted thoracoscopic surgery: evaluation in 173 patients'. The purpose of our article was the assessment of early and long term pain after video-assisted thoracoscopic surgery (VATS), time of incapacity for work and patient satisfaction with scar cosmetics. We found an impressively high number of patients with a very early recovery and rapid reintegration into the working process after VATS. However, as you pointed out there is a signi®cant number of patients with long term complaints after VATS. Approximately 10% had moderate to severe pain at 3 months and 5% at 1 year. We considered this information as interesting for physicians and especially important for counselling patients before a VATS procedure. In our article we did not state that chronic postthoracoscopy pain is signi®cantly lower compared to open thoracotomy. This could only be assessed in a prospective randomized study. In this regard we fully agree. European Journal of Cardio-thoracic Surgery 18 (2000) 738