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Zusammenfassung Hintergrund Die steigende Anzahl an endoskopischen Operationen zeitigt verschiedene Ansprüche an das operative Instrumentarium. Der wohl wichtigste Qualitätsparameter für Klammernahtgeräte ist der Berstungsdruck. Zu dessen Bestimmung finden sich in der Literatur verschiedene experimentelle Aufbauten. All diese Set-ups zeigen jedoch beträchtliche Kritikpunkte. Mit dieser Studie stellen wir ein vollautomatisches und untersucherunabhängiges Berstungsdruckmesssystem vor, das die Situation in vivo weitgehend imitiert. Das experimentelle Set-up zeichnet sich insbesondere dadurch aus, dass nicht nur ein komplettes Bersten registriert, sondern zuverlässig bereits eine sehr frühe – jedoch interventionspflichtige – Leckage detektiert wird (NID = niedrigster interventionspflichtiger Druck). Material und Methode Die Berstungsdruckmessung erfolgte an Gefäßsegmenten von porcinen Aa. carotides communes, der Gefäßverschluss mit dem Klammernahtgerät MicroCutter XCHANGE® der Firma DexteraSurgical. Vor Verschluss wurde das Gefäßsegment mit Flüssigkeit bis zu einem Druck von 80 mmHg gefüllt. Die Flüssigkeit aus 56% Wasser und 44% Glyzerin ergab eine blutähnliche Viskosität von 4,31 ± 0,03 cP. Die Druckerhöhung nach Verschluss erfolgte mit einer definierten Flussrate von 5 ml/min. Eine interventionspflichtige Leckage wurde automatisch detektiert bei einer Abflachung der Druckkurve auf weniger als 5 mmHg/s. Ergebnisse der Validierung Zur Validierung des Softwaresystems wurden insgesamt 30 Klammernahtreihen untersucht. Der visuell durch 2 unabhängige Untersucher ermittelte mittlere Berstungsdruck (mittlere NID) betrug 515,8 mmHg ± 236,3 mmHg. Der maximale lag bei 911 mmHg und der minimale bei 80 mmHg. Der elektronische Berstungsdruck betrug im Mittel 511,8 mmHg ± 239,1 mmHg. Der maximale Druck betrug 911 mmHg und der minimale 80 mmHg. Statistisch zeigte sich eine signifikante Korrelation zwischen dem visuellen und dem elektronischen Berstungsdruck. Schlussfolgerung Mit dem hier vorgestellten Testaufbau gelingt erstmals eine systematische Berstungsdruckmessung, die komplett automatisiert und untersucherunabhängig ist. Der definierte intravasale Druck vor dem Verschluss und die Flüssigkeit mit blutähnlicher Viskosität erlauben es, die intraoperativen Gegebenheiten weitgehend zu imitieren. Durch Definition des Berstungsdrucks als erstes Auftreten einer interventionspflichtigen Leckage (= niedrigster interventionspflichtiger Druck, NID) und nicht als komplettes Bersten lassen sich die Ergebnisse auf den chirurgischen Alltag übertragen.

OBJECTIVES Video-assisted thoracic surgery (VATS) is a complex technique requiring dedicated surgical training. Platforms for such training are scarce and often rely on the use of live animals, which raises ethical concerns. The objective of this study was to develop a box trainer that is dedicated for VATS training and able to reproduce bleeding scenarios. METHODS The developed Tuebingen Thorax Trainer comprises 5 components that are mounted on a human anatomy-like thoracic cavity containing a porcine organ complex. Any standard thoracoscopic instrument can be used. The organ complex is attached to a perfusion module. We assessed the applicability of the system in four 1-day VATS training courses at the Tuebingen Surgical Training Center. Assessment was performed using a questionnaire handed out to all participants. RESULTS Forty participants have been trained with the Tuebingen Thorax Trainer at our institution since November 2016. Thirty-five (87.5%) participants stated that the Tuebingen Thorax Trainer is an adequate model for VATS training. The ex vivo organ complex was reported to be realistic with regards to the level of detail and scale (76%). A large proportion of participants (27.5%) were experienced with VATS and reported having performed >50 procedures before taking the training course. CONCLUSIONS This new training device allows realistic training for VATS procedures. ‘Stagnant hydrostatic perfusion’ permits simulation of reproducible bleeding scenarios. The device is low in production costs and offers a strong resemblance to the clinical scenario. It reduces the use of animal models and contributes to the efforts in making surgical skills training for VATS more accessible.

Purpose Perfusion-mediated tissue cooling has often been described in the literature for thermal ablation therapies of liver tumors. The objective of this study was to investigate the cooling effects of both perfusion and ventilation during laser ablation of lung malignancies. Materials and methods An ex vivo lung model was used to maintain near physiological conditions for the specimens. Fourteen human lung lobes containing only primary lung tumors (non-small cell lung cancer) were used. Laser ablation was carried out using a Nd:YAG laser with a wavelength of 1064 nm and laser fibers with 30 mm diffusing tips. Continuous invasive temperature measurement in 10 mm distance from the laser fiber was performed. Laser power was increased at 2 W increments starting at 10 W up to a maximum power of 12–20 W until a temperature plateau around 60 °C was reached at one sensor. Ventilation and perfusion were discontinued for 6 min each to assess their effects on temperature development. Results The experiments lead to 25 usable temperature profiles. A significant temperature increase was observed for both discontinued ventilation and perfusion. In 6 min without perfusion, the temperature rose about 5.5 °C (mean value, P Conclusion Ventilation- and perfusion-mediated tissue cooling are significant influencing factors on temperature development during thermal ablation. They should be taken into account during the planning and preparation of minimally invasive lung tumor treatment in order to achieve complete ablation.

Histology is the gold standard for confirming thermally induced necrosis. Generally, however, no specimen is obtained from thermal ablation therapy for pathological examination. The aim of this study was to provide evidence for the relationship between temperatures reached and resulting tissue coagulation during laser ablation in a near-physiological ex vivo lung tumor model by combining viability staining and direct temperature measurement. In all, 17 human lung specimens with primary non-small-cell lung cancer (NSCLC) were examined in this study. Organs were resected with curative intent from patients of either gender (5 female, 12 male) with an average age of 65 years (51–78). Here, 11/17 specimens were subjected to interstitial laser thermal ablation in an ex vivo lung perfusion and ventilation model after surgery. A control group of 6/17 specimens was tested for viability without laser ablation. Tissue temperature was measured invasively in real-time during the ablation process using thermocouples. Afterwards, representative slices of all 17 specimens were tested for viability with triphenyltetrazolium chloride (TTC). Maximum tissue temperature Tmax[°C] measured at a distance of 10 and 20 mm from the laser tip and time of temperature exposure were correlated with the diameter of the induced coagulation as ascertained with viability staining. CH evaluated the results. Mean maximum temperature was 75.9°C ± 14.4°C at a distance of 10 mm from the laser tip and 50.3°C ± 14.6°C at a distance of 20 mm, respectively. The mean distance between the coagulation margin and the laser tip was 17.8 mm ± 7.3 mm. We found that coagulation size correlated positively with temperature. There was a clear trend towards the correlation of time over 44°C and ablation depth. Maximum temperatures did not significantly correlate with coagulation size. Laser ablation of lung tumors using the IHLP (isolated human lung perfusion) model represents a possible method for evaluating ex vivo the interrelationships of temperature, time of temperature exposure, and resulting coagulation.

Preoperative chemotherapy improves survival in patients with stage III non-small-cell lung cancer (NSCLC) amenable to resection. We aimed to assess the additional effect of preoperative chemoradiation on tumour resection, pathological response, and survival in these patients.Between Oct 1, 1995, and July 1, 2003, patients with stage IIIA-IIIB NSCLC and invasive mediastinal assessment from 26 participating institutions of the German Lung Cancer Cooperative Group (GLCCG) were randomly assigned to one of two treatment groups. The intervention group were scheduled to receive three cycles of cisplatin and etoposide, followed by twice-daily radiation with concurrent carboplatin and vindesine, and then surgical resection (those with positive resection margins or unresectable disease were offered further twice-daily radiotherapy). The control group were scheduled to receive three cycles of cisplatin and etoposide, followed by surgery, and then further radiotherapy. The primary endpoint was median progression-free survival (PFS) in patients eligible for treatment after randomisation. Secondary endpoints in patients eligible for treatment after randomisation were overall survival (OS) and the proportion of patients undergoing surgery. Secondary endpoints in patients with tumour resection were the proportion with negative resection margins, the proportion with complete resection, the proportion with histopathological response, and the proportion with mediastinal downstaging. Additionally, exploratory (not prespecified) post-hoc analyses in terms of PFS and OS were done on patients not amenable to resection and on further subgroups of patients undergoing resection. Analyses were by intention to treat. This trial is registered on the ClinicalTrials.gov website, number NCT 00176137.558 patients were randomly assigned. 34 patients did not meet inclusion criteria and were excluded. Of 524 eligible patients, 142 of 264 (54%) in the interventional group and 154 of 260 (59%) in the control group underwent surgery; 98 of 264 (37%) and 84 of 260 (32%) underwent complete resection. In patients with complete resection, the proportion of those with mediastinal downstaging (45 of 98 [46%] and 24 of 84 [29%], p=0.02) and pathological response (59 of 98 [60%] and 17 of 84 [20%], p0.0001) favoured the interventional group. However, there was no difference in PFS (primary endpoint) between treatment groups-either in eligible patients (median PFS 9.5 months, range 1.0-117.0 [95% CI 8.3-11.2] vs 10.0 months, range 1.0-111.0 [8.9-11.5], 5-year PFS 16% [11-21] vs 14% [10-19], hazard ratio (HR) 0.99 [0.81-1.19], p=0.87), in those undergoing tumour resection, or in patients with complete resection. In both groups, 35% of patients undergoing surgery received a pneumonectomy (50/142 vs 54/154). In patients receiving a pneumonectomy, treatment-related mortality increased in the interventional group compared with the control group (7/50 [14%] vs 3/54 [6%]).In patients with stage III NSCLC amenable to surgery, preoperative chemoradiation in addition to chemotherapy increases pathological response and mediastinal downstaging, but does not improve survival. After induction with chemoradiation, pneumonectomy should be avoided.German Cancer Aid (Bonn, Germany).

To detect bronchial carcinoma by autofluorescence, we measured the spectra of tumor and normal tissue in situ, in an in vivo model and in vitro by fiber optic spectrometer and two-dimensional resolved microspectroscopy. The in situ measurements were performed in bronchi of nine patients with squamous cell carcinoma during regular bronchoscopy with autofluorescence assistance. The fluorescence was monitored with a fiber optical spectrometer under blue light excitation (lambda=405nm). In an in vivo model, the resected lobe of a lung was perfused under physiological conditions. Tumorous and normal tissues were examined spectroscopically during perfusion and after blood removal and substitution with formol. In another setup the wavelength dependency of autofluorescence was examined on resected parts of physiological bronchi and central bronchial carcinomas. Under the variation of the excitation from 385 to 465nm the autofluorescence response was monitored with a fiber optic spectrometer. For investigation of the origin of autofluorescence, two-dimensional resolved spectroscopy was performed with the SpectraCube system on several sections of tumor and normal tissues All measurements, performed in vivo, in the in vivo model and in vitro agreed, that the main difference of the autofluorescence between tumor and normal bronchus tissue is the intensity of the fluorescences' main peak at 505nm. The signal on tumor tissue is in all cases significantly lower than that of normal tissue. The shape of the autofluorescence peaks is in healthy and carcinoma tissue approximately the same with two characteristic minima at 540 and 580nm. After the preparation with formaldehyde those minima disappeared from the spectra. A comparison with the absorption spectra of hemoglobin showed, that the variation of the spectra may be due to the blood content in the tissue. Two-dimensional spatially resolved spectroscopy showed, that the lower intensity of fluorescence in tumor tissue is due to the irregular and low-concentrated formation of fluorescent structures, which seen to be the elastic structures of bronchial tissue.

In many cases unresectable or recurrent pulmonary metastases do not respond to systemic chemotherapy or the side-effects are not acceptable. Based on the results of our experiments the isolated lung perfusion could improve the option of local chemotherapy. Parameters for lung edema formation (relative increase in weight, gas exchange, histopathology) were evaluated during extracorporal ventilation and reperfusion of lobes resected for lung cancer. Drug concentration was measured in lung tissue, tumour and hilar lymphnodes. Irinotecan was detected in concentrations from 0.06 to 35.3 mg/g in correlation to the content of drug in the perfusate. None of the preparations perfused with a concentration up to 20 times higher than the concentration for systemic application generated a drug-dependent reperfusion edema. A toxic injury of lung parenchyma could be excluded histopathologically. Therefore, we documented that even a perfusion with 2000 mg/l does not cause any relevant acute toxic damages of the lung parenchyma. The transferability of pharmacological data gained through the IHLP is excellent and minimises potential adverse reactions for the patients during phase I trials. As an alternative to systemically applied cytostatic drugs the isolated lung perfusion with irinotecan deserves further attention due to its interesting pharmacological profile with regard to tumor selectivity.

Objective: Multi-modality approaches are increasingly employed to improve prognosis in surgically treated stage III non-small cell lung cancer (NSCLC). Risk and benefit of the preoperative therapeutic chemotherapy or combined radiochemotherapy on surgical morbidity and mortality are still a matter of debate. Methods: In 1995, a national phase III trial was started to compare (arm A) preoperative chemotherapy followed by twice-daily chemoradiation and consecutive surgery, with (arm B) preoperative chemotherapy alone followed by surgery and consecutive radiotherapy. An interim analysis with 277 patients was performed to assess surgical risk and complication rates. Results: Of the 385 patients, 273 (71%) underwent thoracotomy, 130 (73%) in arm A and 143 (69%) in arm B. Of the 273 patients undergoing thoracotomy, 168 had stage IIIB disease. Complete resection (R0) was achieved in 212 patients (78%), 104 in arm A (80%) and 108 in arm B (76%) (PZ n.s.). There was no difference in the proportion of complex resections between treatment arms (41% in arm A; 48% in arm B). Whilst bronchial stump insufficiency (3.8 vs 2.1%) and bleeding requiring re-thoracotomy (1.5 vs 0.7%) prevailed slightly in arm A, the occurrence of pneumonia divided similar on both treatment arms (4.6 vs 4.9%). Surgical mortality reached 6.1% in arm A (8/130) and 5.6% in arm B (6/143) (PZn.s.). Conclusions: In both treatment arms, a similar percentage of patients could be forwarded to surgery, even in stage IIIB disease. Bimodality induction seems to be superior with regard to resection rates (R0) (n.s.), but was associated with a higher complication rate, especially bronchial stump insufficiency. q 2004 Elsevier B.V. All rights reserved.

Objective: Video-assisted mediastinal lymphadenectomy (VAMLA) increases quality of mediastinal lymph node staging in bronchial carcinoma. The video-mediastinoscope allows systematic lymphadenectomy by bimanual preparation. Complete bilateral resection of lymph nodes in stations 1, 2, 3, 4 and 7 (Naruke) can safely be done after visualization of limiting structures (trachea, main bronchi, oesophagus, pericardium, pulmonary artery, aorta, upper vena cava and azygos vein). In this initial study, we compared histopathological findings from VAMLA with final lymph node staging from subsequent thoracotomy. Methods: Between January 2001 and December 2001, 25 patients were operated by VAMLA (among 162 mediastinoscopies), two patients for diagnostic purposes and 23 for staging of bronchial carcinoma. Eighteen patients underwent subsequent thoracotomy for tumor resection and systematic lymphadenectomy. Pathological findings were reviewed. Results: In VAMLA, lymph node dissection of station 2R, 2L and 4R was achieved in 96, 28 and 92%, respectively, whereas resection of lymph nodes in station 7 and 4L was performed in 100%. Other locations were dissected in 44%. A mean of 8.6 lymph nodes were removed in each patient. No residual lymph node tissue was found in the subcarinal compartment at open surgery. When comparing histopathological staging from VAMLA with final pathology, there were no false negative results. Seventeen patients who had N0 disease at VAMLA proved to be N0 or N1 at thoracotomy, one patient diagnosed as N2 at mediastinoscopy had N2 disease at final pathology. The only complication observed in VAMLA was a blood loss of . 100 ml in 12% of patients without need for transfusion or surgical intervention. Conclusion: Mediastinal lymph node staging is improved by VAMLA. A systematic lymphadenectomy is performed bimanually through the video mediastinoscope. The number of lymph nodes removed is doubled compared to standard mediastinoscopy. There were no false negative results at final pathology. This new technique presents the basis for video-assisted thoracic surgery (VATS) lobectomy because complete resection of the mediastinal lymph nodes can be achieved by VAMLA. Potential complications of VAMLA such as injury of major mediastinal vessels, airways, pneumothorax or recurrent laryngeal nerve injury indicate the need for a full thoracic surgical infrastructure. q 2003 Elsevier Science B.V. All rights reserved.

Systemic air embolism is known to rarely complicate blunt chest trauma. However, cerebral infarction caused by air emboli possibly originating from a traumatic pneumatocele has not been previously reported. We report a case of a 46-year-old woman who sustained blunt chest trauma with multiple rib and clavicular fractures, hemothorax and a huge, tense traumatic pneumatocele. She subsequently developed clinical and radiologic features of cerebral infarction. The cerebral infarct is likely to be secondary to cerebral air embolism originating from a traumatic pneumatocele.

OBJECTIVES The management of chest tubes is one of the most critical aspects in patient care in thoracic surgery, and no consensus exists regarding the ideal chest tube management strategy. METHODS Chest tube management protocols and their effects on chest tube therapy were compared at four German specialist thoracic surgery units. Altogether, 79 patients were stratified for underlying disease and type of surgery. A digital chest drainage system was applied to objectify the presence of air leakages. RESULTS In our analysis, the average length of drainage therapy was 4.9 ± 2.8 days. Different chest tube management protocols resulted in a significant degree of scatter between units (P = 0.0348). Higher arbitrary postoperative suction levels (4 kPa) resulted in earlier chest tube removal than lower suction levels (2 kPa) (4.2 ± 2.4 vs 5.4 ± 3.0 days, P = 0.06). Patient discharge following chest tube removal was delayed on average by 3.2 ± 2.9 days. This delay was not correlated with the previous duration of chest tube therapy (Spearman's ρ=-0.15, P = 0.25) in contrast to the total length of hospital stay (ρ = 0.59, P < 0.001).

Study objectives Acquired tracheal and subglottic stenosis frequently leads to severe airway narrowing, which requires repeated interventions, such as dilatation, laser resection, stent implantation, or surgery. To get a more detailed insight into the pathogenesis of this condition, we investigated the expression of profibrotic cytokines and the proliferation of the airway wall in benign human airway stenoses. Methods Specimens from patients with subglottic and tracheal stenosis and stent-related stenoses were obtained (n = 20) for reverse transcription (RT) polymerase chain reaction (PCR) analysis and immunohistochemistry testing. Results Transforming growth factor (TGF)-β 1 messenger RNA expression was significantly increased in biopsy specimens from stent-related stenoses compared to nonstenotic control sections. In contrast, TGF-β 3 and interleukin-1β showed no such differences in messenger RNA expression. Immunohistochemistry revealed a strong matrix-associated, subepithelial expression of TGF-β 1 in tracheal stenosis. Proliferating Ki-67-positive cells were mainly localized in the basal epithelial layer. Only 2 of 16 patients with tracheal stenoses and 3 of 4 patients with stent-related stenoses showed a weak expression of Ki-67-positive cells in the subepithelium. Furthermore, TGF-β 1 dose-dependently enhanced the proliferation of human lung fibroblasts in vitro , even in the presence of mitomycin-C. Conclusion While a weak subepithelial proliferation occurs in stent-related stenoses, the dominant factor in late stages of untreated tracheal stenoses seems to be the high-level expression of TGF-β 1 and the deposition of extracellular matrix.

Summary Background: Expression and amplification of the HER2/neu protooncogene was analyzed in locally advanced NSCLC in a multimodality therapy approach in order to obtain information on the predictive value of HER2/neu for success or failure of neoadjuvant therapy. Methods: In the scope of a prospective randomized phase III-trial, tumor tissue of pre-therapeutically obtained mediastinal lymph node biopsies ( n =105) and corresponding post-surgical resection specimens ( n =44) was analyzed by means of immunohistochemistry (DAKO-Hercep-Test) and fluorescence in situ hybridization (FISH). In 58 of 105 patients with metastatic mediastinal lymph node disease the extent of therapy-induced tumor regression could be established. Results: Concerning HER2/neu expression, 16 lymph node biopsies (15.2%) showed 1+, 2+, or 3+ results. Five of these cases revealed amplification in FISH analysis (4.8%). In 44 corresponding resection specimens, Hercep-Test showed 1+, 2+, or 3+ results in 13 tumors (29.5%). Two of these patients revealed HER2/neu amplification in FISH analysis (4.5%). In patients with HER2/neu expressing tumors a trend towards a less extensive therapy-induced tumor regression could be demonstrated. When comparing pre-therapy and post-surgical results, there was a weak trend towards a selection of HER2/neu expressing tumor tissue in the course of neoadjuvant therapy. Conclusions: Only a limited subcollective of locally advanced NSCLC meets the biological requirements for anti-HER2/neu therapy. HER2/neu positive tumors appeared to be relatively resistant to chemotherapy and radiation treatment, none of these cases having a pathological complete or at least subtotal response in the corresponding resection specimens. This observation requires confirmation in large randomized controlled studies.

Purpose: The alkylating cytostatic prodrug cyclophosphamide is bioactivated by the human cytochrome P450 enzyme system. Since these enzymes are not only expressed in human liver, but also in extrahepatic tissue, local bioactivation of this drug may play an important role in its antineoplastic effects, e.g., chemotherapy of lung tumors. This would require uptake of significant amounts of cyclophosphamide into tumor tissue, which has not yet been demonstrated. Methods: We used a recently developed, ex vivo isolated, ventilated and perfused human lung model to study cyclophosphamide uptake into bronchial carcinoma and healthy lung tissue. Following a standard lobectomy, lung samples containing the tumor were perfused with buffer containing 2 mM cyclophosphamide for 2 h. Cyclophosphamide concentrations in perfusate and healthy peripheral tissue were measured during the perfusion and in tumors at the end of perfusion. Results: In all tissue samples, cyclophosphamide uptake was relatively poor, indicated by a tissue to perfusate ratio of 0.021. Moreover, in tumor samples, cyclophosphamide concentrations were significantly lower (P

We have previously demonstrated expression of cytochrome P 450 3A (CYP3A) protein in pulmonary carcinomas and surrounding normal tissue, using immunohistochemistry. These results suggested that different CYP3A enzymes may be expressed in normal and tumour tissue. Therefore, the aim of the present study was to identify specific CYP3A enzymes expressed in normal human lung and lung tumours. Both normal lung tissue and tumour tissue from eight patients was analyzed for CYP3A4, CYP3A5 and CYP3A7 mRNA using a specific RT-PCR (reverse transcriptase-polymerase chain reaction) method. Identical samples were subjected to immunohistochemical analysis of CYP3A protein. CYP3A5 was the major enzyme of the CYP3A subfamily present at the mRNA level in both normal human lung and lung tumours. CYP3A5 mRNA was detected in normal lung tissue in all eight cases and in tumour tissue in four cases. CYP3A7 mRNA was detected in five cases in normal tissue and in one tumour. Notably, no CYP3A4 mRNA was found in any of the samples. Immunohistochemical staining for CYP3A protein was found in normal lung tissue in each case. Interestingly, all pulmonary carcinomas showed immunostaining for CYP3A, while mRNA for CYP3A enzymes was found in only four cases. In summary, our study indicates a specific expression pattern of the members of the CYP3A subfamily in normal human lung and lung tumours. These findings have potential clinical significance, since it has been recently shown that CYP3A5 catalyzes the activation of the anticancer pro-drugs cyclophosphamide and ifosfamide. Thus, local activation of these agents may take place in pulmonary carcinomas and surrounding normal tissues.

To detect bronchial carcinoma by autofluorescence, we measured in-vivo, in an in-vivo model, and in-vitro the spectra of tumor and normal tissue by a fiber-optic-spectrometer. The main difference between tumor and bronchial tissue is the intensity of the 505 nm main peak. © 2005 SPIE-OSA.