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1.
Cureus ; 16(5): e60088, 2024 May.
Article in English | MEDLINE | ID: mdl-38860077

ABSTRACT

INTRODUCTION: An important goal in every lung resection is airtight closure of the resected lung surface. This can be achieved with several techniques, including clamp resection, stapler, laser, and various high-frequency methods. By quantitatively measuring the air fistula across the resection surface of porcine lungs, two resection techniques were compared in our study: BipoJet dissecting scissors (Aesculap, Inc., Tuttlingen, Germany) and laser (Ceralas HPD®, Biolitec Inc., Jena, Germany). METHODS: Following a stencil, wedge resections were performed in porcine lungs using water-irrigated bipolar scissors and laser (1350 nm, 40 watts, non-contact mode). The volume of the air fistula was then measured. The irrigation technique involved the attachment of an irrigation channel to a pair of standard surgical scissors. A sodium chloride (NaCl) solution was fed at a defined flow rate, along the blades of the scissors onto the parenchyma. This technique was used on a total of 10 specimens each. RESULTS: Somewhat better pneumostasis was achieved with laser resection, though the difference was small and not statistically significant. The flow rate was 124 mL/min/cm² after laser resection and 145 mL/min/cm² after using the BipoJet scissors. The difference was not statistically significant. Water irrigation during resection with the BipoJet scissors prevents the temperature in the tissue from exceeding 100°C thus avoiding tissue carbonization. These scissors offer the following advantages: ease of use, no need to change instruments, no need for staff training, no protective measures, all-in-one incision/coagulation/dissection, low cost, and a clear surgical field due to the irrigation effect. CONCLUSIONS: Resection of lung parenchyma, e.g., during resection of metastases, is easier with BipoJet scissors and comparable to laser resection. This was established both experimentally and by resecting lung metastases.

2.
Ann Afr Med ; 22(1): 101-106, 2023.
Article in English | MEDLINE | ID: mdl-36695230

ABSTRACT

Background: The tumor involvement of lymph nodes (LN) in N2 station is a very important factor for the further therapy decision and the prognosis of lung cancer patients. Today, integrated positron emission tomography-computed tomography (PET-CT) is considered to be the new standard in the staging of bronchial carcinoma. The aim of this study is to investigate the correctness of the clinical staging of the mediastinal LNs in operated patients and to investigate the sensitivity and specificity of the PET-CT examination for mediastinal LNs. Subjects and Methods: In the years 2010-2014, 359 patients underwent surgery for bronchial carcinoma. The histological examination of all mediastinal and hilar LNs was used as a reference to the data from the PET-CT examinations. The correctness of the PET staging, overestimation, and underestimation for the N stage was analyzed. In addition, the "sensitivity," "specificity," and "overall accuracy" of the PET-CT examination with regard to the N2 LNs were calculated. Results: It was found that in 8.9% the staging of the mediastinal N2/N3 LN stations was rated too high by the PET and in 11.2% too low. The study showed a sensitivity of 47.37%, a specificity of 90.07%, and an accuracy of 81.01% for the mediastinal LNs. Conclusion: Our study confirms the limited ability of integrated PET-CT in staging the mediastinal LNs. We, therefore, recommend a histological examination of the LNs in patients with PET-positive N2 LNs to avoid false-positive results and to initiate correct therapy.


Résumé Contexte: L'implication tumorale des ganglions lymphatiques (LN) au stade N2 est un facteur très important pour la décision thérapeutique ultérieure et le pronostic des patients atteints de cancer du poumon. Aujourd'hui, la tomographie par émission de positons intégrée (TEP-CT) est considérée comme être la nouvelle norme dans la stadification du carcinome bronchique. Le but de cette étude est d'étudier l'exactitude de la stadification clinique des ganglions lymphatiques médiastinaux chez les patients opérés et d'étudier la sensibilité et la spécificité de l'examen TEP-TDM pour les ganglions lymphatiques médiastinaux. Sujets et méthodes: Dans les années 2010 à 2014, 359 patients ont été opérés d'un carcinome bronchique. L'examen histologique de tous les LN médiastinaux et hilaires a servi de référence aux données des examens PET-CT. La justesse de la mise en scène PET, la surestimation et la sous-estimation pour le stade N ont été analysées. De plus, la " sensibilité ", la " spécificité " et la " précision globale " de l'examen PET-CT en ce qui concerne les N2 LNs ont été calculés. Résultats: Il a été constaté que dans 8,9 % des cas, la mise en scène du médiastin N2/ Les stages N3 LN ont été jugées trop élevées par le PET et dans 11,2 % trop faibles. L'étude a montré une sensibilité de 47,37%, une spécificité de 90,07%, et une précision de 81,01 % pour les LN médiastinaux. Conclusion: Notre étude confirme la capacité limitée de la TEP-TDM intégrée dans la stadification les LN médiastinaux. Nous recommandons donc un examen histologique des ganglions lymphatiques chez les patients avec des ganglions lymphatiques N2 positifs à la TEP pour éviter résultats faussement positifs et d'initier un traitement correct Mots-clés: Cancer du poumon, tomographie par émission de positrons/tomodensitométrie, stadification.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Carcinoma, Non-Small-Cell Lung/surgery , Positron Emission Tomography Computed Tomography , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/surgery , Tomography, X-Ray Computed/methods , Neoplasm Staging , Lymph Nodes/diagnostic imaging , Lymph Nodes/pathology , Retrospective Studies
3.
Interact Cardiovasc Thorac Surg ; 30(3): 477-482, 2020 03 01.
Article in English | MEDLINE | ID: mdl-31778173

ABSTRACT

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.


Subject(s)
Models, Anatomic , Simulation Training/methods , Thoracic Surgery, Video-Assisted/education , Animals , Humans , Surveys and Questionnaires , Swine
4.
Zentralbl Chir ; 142(5): 457-463, 2017 Oct.
Article in German | MEDLINE | ID: mdl-28633187

ABSTRACT

Background A growing number of operations are performed using minimally invasive techniques. Therefore, a lot of new requirements must be met by the staplers currently available. At the present time, the most widely used methods of minimally invasive vascular occlusion involve high-frequency energy, clips, and staplers. The most important quality parameter is burst pressure, which is measured with a variety of experimental set-ups, all of which are subject to criticism. With this study, we want to introduce a fully automated vascular burst pressure measuring system that largely mimics physiological conditions. An important feature of this set-up is the detection of very early leakage from the staple line (FAIR Leakage = First Appearance of Leakage requiring Intervention). Material and Methods Burst pressure was measured in vessel segments of porcine common carotid arteries. For vascular occlusion, we used the stapler device Micro Cutter XCHANGE® by DexteraSurgical. Prior to closure, the vessel was filled to a pressure of 80 mmHg. The pressure was increased at a defined flow rate. Burst pressure was defined as staple line leakage requiring intervention. Results and Validation 30 staple lines were examined. The average burst pressure visually determined by two independent investigators was 515.8 mmHg ± 236.3 mmHg. Maximal burst pressure was 911 mmHg, and minimal burst pressure 80 mmHg. The average burst pressure detected electronically was 511.8 mmHg ± 239.1 mmHg. Statistically, there was a highly significant correlation of visually and electronically detected burst pressures. Conclusion This is the first experimental set-up for a systematic burst pressure test that is fully automated and therefore eliminates any bias related to the investigator. The experimental set-up with a defined intravascular pressure prior to closure and the use of a liquid with blood-like viscosity enabled us to largely mimic intraoperative conditions. Since burst pressure is not defined as a complete rupture of the staple line, but as the moment of first occurrence of leakage requiring intervention, the results can be transferred into daily surgical practice.


Subject(s)
Anastomotic Leak/diagnosis , Blood Vessels/physiopathology , Carotid Artery, Common/surgery , Computer Simulation , Microsurgery/methods , Minimally Invasive Surgical Procedures/methods , Surgical Wound Dehiscence/physiopathology , Anastomotic Leak/physiopathology , Animals , Automation , Blood Pressure/physiology , Carotid Artery, Common/physiopathology , In Vitro Techniques , Laparoscopy , Surgical Stapling , Swine , Thoracic Surgical Procedures
5.
J Clin Oncol ; 31(19): 2396-403, 2013 Jul 01.
Article in English | MEDLINE | ID: mdl-23715567

ABSTRACT

PURPOSE: The MAGE-A3 protein is expressed in approximately 35% of patients with resectable non-small-cell lung cancer (NSCLC). Several immunization approaches against the MAGE-A3 antigen have shown few, but often long-lasting, clinical responses in patients with metastatic melanoma. PATIENTS AND METHODS: A double-blind, randomized, placebo-controlled phase II study was performed assessing clinical activity, immunologic response, and safety following immunization with recombinant MAGE-A3 protein combined with an immunostimulant (13 doses over 27 months) in completely resected MAGE-A3-positive stage IB to II NSCLC. The primary end point was disease-free interval (DFI). RESULTS: Patients were randomly assigned to either MAGE-A3 immunotherapeutic (n = 122) or placebo (n = 60). After a median postresection period of 44 months, recurrence was observed in 35% of patients in the MAGE-A3 arm and 43% in the placebo arm. No statistically significant improvement in DFI (hazard ratio [HR], 0.75, 95% CI, 0.46 to 1.23; two-sided P = .254), disease-free survival (DFS; HR, 0.76; 95% CI, 0.48 to 1.21; P = .248), or overall survival (HR, 0.81; 95% CI, 0.47 to 1.40; P = .454) was observed. Corresponding analysis after a median of 70 months of follow-up revealed a similar trend for DFI and DFS. All patients receiving the active treatment showed a humoral immune response to the MAGE-A3 antigen, although no correlation was observed with outcome. No significant toxicity was observed. CONCLUSION: In this early development study with a limited number of patients, postoperative MAGE-A3 immunization proved to be feasible with minimal toxicity. These results are being investigated further in a large phase III study.


Subject(s)
Adjuvants, Immunologic/therapeutic use , Antigens, Neoplasm/immunology , Cancer Vaccines/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/immunology , Immunotherapy/methods , Lung Neoplasms/drug therapy , Lung Neoplasms/immunology , Molecular Targeted Therapy/methods , Neoplasm Proteins/immunology , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/surgery , Disease-Free Survival , Double-Blind Method , Europe , Female , Gene Expression Regulation, Neoplastic , Humans , Kaplan-Meier Estimate , Lung Neoplasms/surgery , Male , Middle Aged , Recombinant Proteins/therapeutic use , Treatment Outcome
6.
Interact Cardiovasc Thorac Surg ; 15(4): 622-6, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22753431

ABSTRACT

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).


Subject(s)
Chest Tubes , Drainage/instrumentation , Pneumonectomy , Practice Patterns, Physicians' , Aged , Device Removal , Drainage/adverse effects , Female , Germany , Humans , Kaplan-Meier Estimate , Length of Stay , Male , Middle Aged , Pneumonectomy/adverse effects , Postoperative Care , Prospective Studies , Time Factors
7.
Thorac Cardiovasc Surg ; 60 Suppl 2: e16-8, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22549758

ABSTRACT

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.


Subject(s)
Air , Cerebral Infarction/etiology , Cysts/complications , Lung Diseases/complications , Multiple Trauma/complications , Thoracic Injuries/complications , Wounds, Nonpenetrating/complications , Cerebral Infarction/diagnosis , Cerebral Infarction/surgery , Clavicle/injuries , Cysts/diagnosis , Cysts/etiology , Cysts/surgery , Female , Follow-Up Studies , Hemothorax/complications , Humans , Lung Diseases/diagnosis , Lung Diseases/surgery , Middle Aged , Rare Diseases , Rib Fractures/complications , Rib Fractures/etiology , Thoracotomy , Treatment Outcome , Wounds, Nonpenetrating/etiology
8.
MAGMA ; 25(1): 63-74, 2012 Feb.
Article in English | MEDLINE | ID: mdl-21656191

ABSTRACT

OBJECT: 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. MATERIALS AND METHODS: 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. 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. CONCLUSION: 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.


Subject(s)
Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/surgery , Laser Therapy/methods , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Aged , Air , Algorithms , Diagnostic Imaging/methods , Equipment Design , Female , Humans , Male , Middle Aged , Models, Statistical , Necrosis , Perfusion , Temperature , Tetrazolium Salts/pharmacology
9.
Eur J Radiol ; 80(2): 569-72, 2011 Nov.
Article in English | MEDLINE | ID: mdl-20646885

ABSTRACT

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<0.05); without ventilation it increased about 7.0 °C (mean value, P<0.05). 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.


Subject(s)
Hyperthermia, Induced , Laser Therapy/methods , Lung Neoplasms/therapy , Heart-Lung Machine , Humans , In Vitro Techniques , Necrosis , Perfusion , Statistics, Nonparametric , Temperature
10.
Lancet Oncol ; 9(7): 636-48, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18583190

ABSTRACT

BACKGROUND: 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. METHODS: 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. FINDINGS: 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%], p<0.0001) 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%]). INTERPRETATION: 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. FUNDING: German Cancer Aid (Bonn, Germany).


Subject(s)
Antineoplastic Agents/administration & dosage , Carcinoma/therapy , Lung Neoplasms/therapy , Pneumonectomy , Adult , Aged , Carcinoma/mortality , Carcinoma/pathology , Chemotherapy, Adjuvant , Drug Administration Schedule , Female , Humans , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Radiotherapy Dosage , Radiotherapy, Adjuvant , Treatment Outcome
11.
Interact Cardiovasc Thorac Surg ; 6(5): 583-7, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17670737

ABSTRACT

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.


Subject(s)
Antineoplastic Agents, Phytogenic/toxicity , Camptothecin/analogs & derivatives , Lung/drug effects , Pulmonary Circulation/drug effects , Pulmonary Edema/chemically induced , Antineoplastic Agents, Phytogenic/metabolism , Camptothecin/metabolism , Camptothecin/toxicity , Capillaries/drug effects , Capillaries/pathology , Dose-Response Relationship, Drug , Humans , Irinotecan , Lung/blood supply , Lung/metabolism , Lung/pathology , Lung Neoplasms/metabolism , Lymph Nodes/metabolism , Organ Culture Techniques , Organ Size/drug effects , Oxygen/metabolism , Perfusion , Pulmonary Edema/pathology , Pulmonary Edema/physiopathology , Pulmonary Gas Exchange/drug effects , Time Factors
12.
Chest ; 129(5): 1298-304, 2006 May.
Article in English | MEDLINE | ID: mdl-16685022

ABSTRACT

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)-beta1 messenger RNA expression was significantly increased in biopsy specimens from stent-related stenoses compared to nonstenotic control sections. In contrast, TGF-beta3 and interleukin-1beta showed no such differences in messenger RNA expression. Immunohistochemistry revealed a strong matrix-associated, subepithelial expression of TGF-beta1 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-beta1 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-beta1 and the deposition of extracellular matrix.


Subject(s)
Extracellular Matrix/metabolism , Gene Expression , RNA, Messenger/genetics , Tracheal Stenosis/metabolism , Transforming Growth Factor beta/genetics , Biomarkers/metabolism , Biopsy , Cell Proliferation , Cells, Cultured , Electrophoresis, Agar Gel , Fibroblasts/metabolism , Fibroblasts/pathology , Humans , Immunohistochemistry , Interleukin-1/genetics , Interleukin-1/metabolism , Ki-67 Antigen/metabolism , Lung/metabolism , Lung/pathology , Prognosis , Reverse Transcriptase Polymerase Chain Reaction , Tracheal Stenosis/pathology , Transforming Growth Factor beta/metabolism , Transforming Growth Factor beta1 , Transforming Growth Factor beta3
13.
Lung Cancer ; 48(1): 59-67, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15777971

ABSTRACT

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.


Subject(s)
Biomarkers, Tumor/analysis , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Gene Amplification , Gene Expression Profiling , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Receptor, ErbB-2/biosynthesis , Adult , Aged , Carcinoma, Non-Small-Cell Lung/radiotherapy , Carcinoma, Non-Small-Cell Lung/surgery , Drug Resistance, Neoplasm , Female , Gene Expression Regulation, Neoplastic , Genes, erbB-2 , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Lung Neoplasms/radiotherapy , Lung Neoplasms/surgery , Male , Middle Aged , Neoadjuvant Therapy , Predictive Value of Tests , Treatment Outcome
14.
Eur J Cardiothorac Surg ; 26(6): 1205-1210, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15678591

ABSTRACT

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 358 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%) (P=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 in 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) (P=n.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.


Subject(s)
Carcinoma, Non-Small-Cell Lung/surgery , Lung Neoplasms/surgery , Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/radiotherapy , Combined Modality Therapy/methods , Female , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/radiotherapy , Male , Middle Aged , Neoplasm Staging , Pneumonia/etiology , Postoperative Complications/etiology , Preoperative Care/methods , Reoperation , Respiratory Insufficiency/etiology , Risk Factors , Thoracotomy/methods , Treatment Outcome
15.
Eur J Cardiothorac Surg ; 24(2): 192-5, 2003 Aug.
Article in English | MEDLINE | ID: mdl-12895606

ABSTRACT

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.


Subject(s)
Carcinoma, Bronchogenic/surgery , Lung Neoplasms/surgery , Lymph Node Excision/methods , Mediastinoscopy/methods , Video-Assisted Surgery , Carcinoma, Bronchogenic/pathology , Humans , Lung Neoplasms/pathology , Neoplasm Staging
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