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3.
Pneumologie ; 72(9): 617-623, 2018 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-30071539

RESUMO

Performing rebiopsies for primary lung cancer and/or their metastases is becoming more and more prominent in daily practice, as the therapeutical spectrum increases and some newer strategies are dependent on immunohistochemical and/or molecular factors. In general, nearly all recurrent lesions or metastases can be reached. However, frequently invasive procedures are necessary with the need to carefully weigh risks and benefits of rebiopsies for the patient in each case. In this review indications for recurrent and progressive disease as well as risks are discussed and alternatives to rebiopsies are shown. This work is the joint opinion from both the endoscopic and thoracic oncology sections of the German Society of Pneumology (DGP).


Assuntos
Biópsia , Neoplasias Pulmonares/patologia , Pneumologia , Alemanha , Humanos , Sociedades Médicas
4.
Pneumologie ; 71(11): 798-812, 2017 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-29139101

RESUMO

Endobronchial Ultrasound (EBUS) with the two modalities curved and radial EBUS significantly improved the diagnostics in several pulmonary diseases. The examination and staging of mediastinal and hilar lymph nodes in patients with known or suspected lung malignancy as well as the evaluation of unknown pulmonary or mediastinal lesions can be achieved with minimal invasive means when using EBUS. More invasive surgical procedures for diagnostic purposes can be omitted. The diagnostic yield also increases when EBUS is applied in sarcoidosis or mediastinal lymph node tuberculosis but only to some extend in case of lymphoma. Samples obtained by EBUS-TBNA should be handled efficiently to allow molecular analysis in lung cancer. EBUS is a safe procedure, and complication rate is extremely low. Further advances of the EBUS technology focus on improving analysis of the information provided by the ultrasound image and a better tissue sampling by developing of new EBUS bronchoscopes and TBNA-needles.


Assuntos
Broncoscopia/métodos , Endossonografia/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias do Mediastino/diagnóstico por imagem , Biópsia por Agulha , Humanos , Neoplasias Pulmonares/patologia , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Linfoma/diagnóstico por imagem , Linfoma/patologia , Neoplasias do Mediastino/patologia , Estadiamento de Neoplasias , Sarcoidose Pulmonar/diagnóstico por imagem , Sarcoidose Pulmonar/patologia , Sensibilidade e Especificidade , Tuberculose dos Linfonodos/diagnóstico por imagem , Tuberculose dos Linfonodos/patologia
5.
Ann Oncol ; 28(5): 1084-1089, 2017 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-28453703

RESUMO

Background: Heart exposure to ionizing irradiation can cause ischaemic heart disease. The partial heart volume receiving ≥5 Gy (heartV5) was supposed to be an independent prognostic factor for survival after radiochemotherapy for locally advanced non-small-cell lung cancer (NSCLC). But validation of the latter hypothesis is needed under the concurrent risks of lung cancer patients. Patients and methods: The ESPATUE phase III trial recruited patients with potentially operable IIIA(N2)/selected IIIB NSCLC between 01/2004 and 01/2013. Cisplatin/paclitaxel induction chemotherapy was given followed by neoadjuvant radiochemotherapy (RT/CT) to 45 Gy (1.5 Gy bid/concurrent cisplatin/vinorelbine). Operable patients were randomized to definitive RT/CT(arm A) or surgery (arm B) and therefore were treated at two different total dose levels of radiotherapy. HeartV5 and mean heart dose (MHD) were obtained from the 3D radiotherapy plans, the prognostic value was analysed using multivariable proportional hazard analysis. Results: A total of 161 patients were randomized in ESPATUE, heartV5 and MHD were obtained from the 3D radiotherapy plans for 155 of these [male/female:105/50, median age 58 (33-74) years, stage IIIA/IIIB: 54/101]. Power analysis revealed a power of 80% of this dataset to detect a prognostic value of heartV5 of the size found in RTOG 0617. Multivariable analysis did not identify heartV5 as an independent prognostic factor for survival adjusting for tumour and clinical characteristics with [hazard ratio 1.005 (0.995-1.015), P = 0.30] or without lower lobe tumour location [hazard ratio 0.999 (0.986-1.012), P = 0.83]. There was no influence of heartV5 on death without tumour progression. Tumour progression, and pneumonia were the leading causes of death representing 65% and 14% of the observed deaths. Conclusions: HeartV5 could not be validated as an independent prognostic factor for survival after neoadjuvant or definitive conformal radiochemotherapy. Tumour progression was the predominant cause of death. Register No: Z5 - 22461/2 - 2002-017 (German Federal Office for Radiation Protection).


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Quimiorradioterapia/efeitos adversos , Relação Dose-Resposta à Radiação , Feminino , Coração/efeitos da radiação , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Lesões por Radiação/diagnóstico , Lesões por Radiação/etiologia , Resultado do Tratamento
6.
Chirurg ; 86(5): 410-8, 2015 May.
Artigo em Alemão | MEDLINE | ID: mdl-25794450

RESUMO

BACKGROUND: Complications cannot always be avoided and their treatment is an integral component of a high quality medical treatment. Complications of the central airways are rare but necessitate supportive treatment by an experienced thoracic surgeon. OBJECTIVE: The reader should become acquainted with measures to prevent complications, to recognize and treat complications early and should understand the necessity for an interdisciplinary approach. MATERIAL AND METHODS: A selective literature research was supplemented by personal experiences and complemented with prospectively collected photographs. RESULTS: There are risk constellations for the appearance of all the mentioned complications which the surgeon needs to know in order to be able to take measures for early detection of complications. Iatrogenic tracheal injuries and bronchial stump fistulae are rare (< 5 %) whereas recurrent laryngeal nerve palsy after left-sided pneumonectomy occurs in up to 30 % of cases. DISCUSSION: After the occurrence of complications at the latest, it is very important to include experienced thoracic surgeons and other specialists when necessary to protect the patient from further damage.


Assuntos
Anastomose Cirúrgica , Brônquios/lesões , Brônquios/cirurgia , Complicações Pós-Operatórias/cirurgia , Deiscência da Ferida Operatória/cirurgia , Procedimentos Cirúrgicos Torácicos/efeitos adversos , Traqueia/lesões , Paralisia das Pregas Vocais/cirurgia , Fístula Brônquica/prevenção & controle , Fístula Brônquica/cirurgia , Intervenção Médica Precoce , Humanos , Intubação Intratraqueal/efeitos adversos , Pneumonectomia/efeitos adversos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Reoperação , Fatores de Risco , Deiscência da Ferida Operatória/prevenção & controle , Traqueia/cirurgia , Paralisia das Pregas Vocais/prevenção & controle
7.
Lung Cancer ; 88(1): 34-41, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25708529

RESUMO

OBJECTIVES: Pulmonary adenocarcinomas (ADC) can be sub-grouped based on dominant oncogenic drivers. EGFR mutations define an entity of metastatic ADC with favorable prognosis and high susceptibility to EGFR tyrosine kinase inhibition. In contrast, the clinical impact of additional ERBB family members in ADC is less defined. To this end we prospectively studied HER2 expression, gene amplification, and mutation in relation to outcome of patients with advanced or metastatic ADC. MATERIALS AND METHODS: Diagnostic tumor biopsies from 193 sequential patients with stage III/IV ADC were prospectively studied for HER2 expression by immunohistochemistry (IHC). Cases with IHC scores 2+ or 3+ were analyzed by HER2 chromogenic in situ hybridization (CISH), and sequencing of HER2 exons 20 and 23. Additional prospectively determined biomarkers included PTEN, cMET, pAKT, and pERK expression, KRAS, EGFR, BRAF and PIK3CA mutations, and ALK fluorescence ISH (FISH). RESULTS AND CONCLUSION: HER2-IHC was feasible in 176 (91.2%) cases. Of 53 (30%) cases with IHC scores 2+/3+, 45 (85%) could be studied by CISH and 34 (64%) by sequencing. The lower number of HER2-mutational analyses resulted from exhaustion of tumor tissue and DNA following mutational analysis of KRAS, EGFR, BRAF and PIK3CA. HER2 amplification was detected in 4 cases (2.3%), while no mutation was found. HER2 expression correlated with expression of pAKT and cMET. Expression of HER2 and pAKT was associated with favorable overall survival in stage IV disease. HER2-expressing ADC more frequently harbored KRAS mutations, while HER2 expression was absent in all 4 cases with BRAF mutation. HER2-IHC was not predictive of HER2 gene amplification or mutation, which both were rare events in prospectively studied patients with advanced or metastatic ADC. Expression of HER2 and pAKT define a population of patients with stage IV ADC with a distinct disease course, who could benefit from specifically tailored pharmacotherapies.


Assuntos
Adenocarcinoma/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias Pulmonares/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Receptor ErbB-2/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Idoso , Análise Mutacional de DNA , Feminino , Amplificação de Genes , Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor ErbB-2/genética , Transdução de Sinais
8.
Onco Targets Ther ; 7: 2061-5, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25419143

RESUMO

BACKGROUND: The assessment of an increasing number of molecular markers is becoming a standard requirement from endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) specimens. However, it is unclear how many needle passes should be performed and the amount of lung cancer cells that should be sent for molecular analyses. The objective of this study was to determine if it is feasible to divide the material obtained by EBUS-TBNA to allow for molecular analysis without compromising the accuracy of mediastinal staging. OBJECTIVE: We aimed to determine if dividing EBUS-TBNA specimens has a negative impact on either histopathological diagnosis or molecular analysis. METHODS: EBUS-TBNA was performed in 249 enlarged lymph nodes. Negative or ambiguous histopathological results were confirmed by surgical means and clinical follow-up over 6 months. The tissue obtained by EBUS-TBNA was placed onto a glass slide and divided for histopathological workup and molecular analysis. The number of passes was recorded. Both the accuracy of the mediastinal lymph node staging and the applicability of the sample division for molecular analysis were assessed. RESULTS: Each lymph node was punctured an average of 3.18 times and division of the obtained material for diagnosis and molecular analysis was feasible in all cases. The sensitivity and accuracy of the mediastinal lymph node staging were 96.6% and 97.6%, respectively. A cytokeratin (CK)-19-mRNA concentration-based molecular test was feasible in 74.1% of cases. CONCLUSION: Dividing EBUS-TBNA samples for both histopathological diagnosis and molecular testing is feasible and does not compromise the accuracy of mediastinal staging. This method may be an alternative to taking additional needle passes for molecular analyses.

9.
Pneumologie ; 68(11): 719-26, 2014 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-25003906

RESUMO

Molecular biomarkers are becoming increasingly significant in the workup of lung carcinoma patients. They assist in diagnosis, selecting the most adequate therapy and determining prognosis. Obtaining blood based biomarkers or volatile markers in exhaled breath may provide a less invasive method in the future. For the time being, bronchoscopy is still the method of choice to obtain specimen and assess tissue based biomarkers. The techniques how specimen are collected and processed for analysis are of paramount importance.


Assuntos
Biomarcadores Tumorais/metabolismo , Brônquios/metabolismo , Broncoscopia/métodos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismo , Proteínas de Neoplasias/metabolismo , Humanos , Neoplasias Pulmonares/terapia , Cuidados Pré-Operatórios/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
10.
Ann Oncol ; 24(11): 2866-70, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24026539

RESUMO

BACKGROUND: Endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA) is a well-established method to assess mediastinal lymph nodes for lung cancer. However, a proportion of patients require further investigation, due to the low negative predictive value (NPV). The objective of this study was to determine whether the assessment of short stature homeobox 2 (SHOX2) DNA methylation level in lymph node tissue obtained by EBUS-TBNA improves the accuracy of mediastinal staging. PATIENTS AND METHODS: EBUS-TBNA was carried out for suspicious lymph nodes of 154 patients. Negative or ambiguous histological results were confirmed by surgical means and clinical follow-up over 6 months. EBUS-TBNA was assessed on 80 positive and 85 negative classified lymph nodes and compared with the result of the SHOX2 DNA methylation real-time PCR analysis. Relative methylation measured by delta-delta cycle threshold (ΔΔCt) was used to classify the samples. Clinical performance of the EBUS-TBNA procedure with and without the additional SHOX2 assessment was calculated against the final classification according to the gold standard. RESULTS: Based on data from 105 patients, an average 80-fold increase in the SHOX2 methylation level was measured for positive compared with negative lymph nodes. SHOX2 results with a ΔΔCt value of <6.5 indicate positive lymph nodes. Applying this molecular analysis to EBUS-TBNA cases, not diagnosed by pathologic assessment, the sensitivity of staging was improved by 17%-99%. The NPV increased from 80% to 99%. CONCLUSIONS: The combination of EBUS-TBNA and SHOX2 methylation level strongly improves the assessment of the nodal status by identifying additional malignant lesions and confirming benign nodes and therefore avoiding invasive follow-up procedures.


Assuntos
Broncoscópios , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Proteínas de Homeodomínio/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Linfonodos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Metilação de DNA/genética , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Linfonodos/metabolismo , Metástase Linfática/diagnóstico , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias
11.
Gene Ther ; 20(10): 1022-8, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23719068

RESUMO

Revealing the lung tumor genome has directed the current treatment strategies toward targeted therapy. First line treatments targeting the genome of lung tumor cells have been approved and are on the market. However, they are limited by the small number of patients with the current investigated genetic mutations. Novel treatment administration modalities have been also investigated in an effort to increase the local drug deposition and disease control. In the current study, we investigated the safety of the new nonviral vector 2-diethylaminoethyl-dextran methyl methacrylate copolymer (DDMC; Ryujyu Science), which belongs to the 2-diethylaminoethyl-dextran family by aerosol administration. Thirty male BALBC mice, 2 month old, were included and divided into three groups. However, pathological findings indicated severe emphysema within three aerosol sessions. In addition, the CytoViva technique was applied for the first time to display the nonviral particles within the pulmonary tissue and emphysema lesions, and a spectral library of the nonviral vector was also established. Although our results in BALBC mice prevented us from further investigation of the DDMC nonviral vector as a vehicle for gene therapy, further investigation in animals with larger airways is warranted to properly evaluate the safety of the vector.


Assuntos
DEAE-Dextrano/toxicidade , Enfisema/induzido quimicamente , Terapia Genética , Pulmão/patologia , Metilmetacrilato/toxicidade , Administração por Inalação , Animais , DEAE-Dextrano/administração & dosagem , Terapia Genética/efeitos adversos , Terapia Genética/métodos , Neoplasias Pulmonares/terapia , Masculino , Metilmetacrilato/administração & dosagem , Camundongos , Camundongos Endogâmicos BALB C , Distribuição Aleatória
12.
Dtsch Med Wochenschr ; 138(11): 530-5, 2013 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-23463474

RESUMO

Hemoptysis (coughing up blood) is an extremely alarming situation for the patient, caused by various different underlying diseases. First of all, a peripheral venous catheter should be placed and oxygen should be supplied as patients are threatened by impaired gas exchange caused by the bleeding. Bronchoscopy should be performed immediately, although computed tomography of the thorax may give valuable diagnostic information and should be performed if permitted by the clinical situation. Rigid bronchoscopy should be performed as it allows a broader spectrum of therapeutic options.


Assuntos
Broncoscopia/métodos , Cateterismo Venoso Central , Hemoptise/diagnóstico , Hemoptise/terapia , Oxigenoterapia/métodos , Radiografia Torácica/métodos , Tomografia Computadorizada por Raios X/métodos , Hemoptise/etiologia , Humanos
13.
Pathologe ; 34(4): 305-9, 2013 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-23503854

RESUMO

BACKGROUND: Definitive diagnosis of unclear pulmonary lesions is mainly based on morphological methods. In addition to a neoplasm, inflammatory reactions, in particular tuberculosis (TB), have to be considered in most cases. Therefore, the aim of this work was to determine whether established methods used in general pathology can be efficiently used with cytological material. MATERIALS AND METHODS: An established polymerase chain reaction (PCR) protocol for the detection of Mycobacterium tuberculosis complex (Mtc) DNA in fixed specimens was conducted on fixed material available as an assay for liquid-based cytology (LBC). CytoLyt®-fixed material of 45 patients with clinically suspected TB or other mycobacteriosis were selected and were initially tested cytologically. In cases of absent tumor cells, PCR for detection of Mtc DNA and Ziehl-Neelsen stain (ZN) were performed. RESULTS: In 9 patients (20 %), Mtc DNA was found by PCR. The following methods were used to obtain material: catheter biopsy (5), needle biopsy (2), transbronchial needle aspiration (1), and bronchoalveolar lavage (1). Cytologically an inflammatory reaction was observed in all cases. In 2 patients, a history of TB, in 2 further cases either silicosis or a posttransplant situation was known. In cases with a positive PCR, 7 patients (78 %) were positive in ZN and 3 patients (33.3 %) in TB culture (15.5 % vs. 6.7 % of the total cohort); however, the material used for investigation was not always from identical sources, respectively. In 36 out of 45 patients, both PCR and ZN were negative for the detection of Mtc DNA. CONCLUSION: The material intended for LBC can be used for detection of TB with ZN and Mtc PCR.


Assuntos
Corantes , Reação em Cadeia da Polimerase/métodos , Tuberculose Pulmonar/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Técnicas Bacteriológicas , Biópsia , DNA Bacteriano/análise , DNA Bacteriano/genética , Diagnóstico Diferencial , Feminino , Humanos , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/genética , Valor Preditivo dos Testes , Tuberculose Pulmonar/microbiologia
15.
Pathologe ; 33(4): 308-15, 2012 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-22752354

RESUMO

Endobronchial ultrasound-guided transbronchial fine needle aspiration (EBUS-TBNA) has become an important tool in the diagnosis and staging of malignant tumors of the lungs and mediastinum. Rapid on-site evaluation (ROSE) denotes a cytomorphological diagnostic procedure that allows assessment of the adequacy and accuracy of the material obtained during bronchoscopy within a few minutes in or near the bronchoscopy suite (on-site) using a quick staining of smears. This results in a significant decrease in the number of repeated bronchoscopy procedures required to recover an adequate biopsy sample and is therefore both time and cost effective. The obtained material can be further assessed as conventional cytological specimens or alternatively using the thin-prep technique for definitive cytopathology diagnosis and/or embedded in paraffin for immunohistochemical or molecular analyses such as DNA sequencing or flow cytometry.


Assuntos
Neoplasias Pulmonares/patologia , Neoplasias do Mediastino/patologia , Algoritmos , Biópsia por Agulha Fina/instrumentação , Biópsia por Agulha , Broncoscopia/instrumentação , Técnicas Citológicas/métodos , Desenho de Equipamento , Humanos , Pulmão/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Metástase Linfática/patologia , Neoplasias do Mediastino/diagnóstico por imagem , Mediastinoscopia , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Estudos de Tempo e Movimento , Tomografia Computadorizada por Raios X , Ultrassonografia de Intervenção/instrumentação
17.
Dtsch Med Wochenschr ; 134(46): 2346-50, 2009 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-19894203

RESUMO

Flexible bronchoscopy is one of the most important diagnostic procedures in respiratory medicine. The investigator operates in a vital organ and therefore must face a broad range of potential complications. This article provides an overview of all important complications associated with flexible bronchoscopy. It is further discussed how this risk can be minimized. A skillfull team, close monitoring and readily available resuscitation facilities are mandatory to avoid and to deal with major complications.


Assuntos
Broncoscopia/efeitos adversos , Broncoscopia/métodos , Gestão de Riscos/métodos , Anestesia Local , Lavagem Broncoalveolar/efeitos adversos , Lavagem Broncoalveolar/métodos , Humanos , Equipe de Assistência ao Paciente , Doenças Respiratórias/diagnóstico , Ressuscitação/métodos , Fatores de Risco
18.
Pneumologie ; 61(3): 176-80, 2007 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-17342579

RESUMO

We describe the case of a 76-year-old immunocompetent man suspected to have lung cancer in the right upper lobe on the basis of radiographic and clinical findings. The tumour could not be confirmed histologically by transbronchial biopsy. In the fluorodeoxyglucose positron emission tomography (FDG-PET) we found a significantly elevated standard uptake value (SUV) of 13.4. The patient underwent thoracotomy with excision of the tumour, the histological diagnosis was chronic pneumonia. Tissue culture revealed Nocardia spp. Using 16-rDNA-gene sequence analysis the species was identified as Nocardia abscessus. The patient was treated with trimethoprim-sulfamethoxazol regarding the susceptibility profile and improved remarkably both clinically and radiographically.


Assuntos
Antibacterianos/uso terapêutico , Neoplasias Pulmonares/diagnóstico por imagem , Nocardiose/diagnóstico por imagem , Idoso , Diagnóstico Diferencial , Quimioterapia Combinada , Fluordesoxiglucose F18 , Humanos , Masculino , Tomografia por Emissão de Pósitrons , Radiografia , Radioisótopos , Resultado do Tratamento
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