[Endobronchial presentation of an inflammatory myofibroblastic tumor]. / Présentation endobronchique d'une tumeur myofibroblastique inflammatoire.

INTRODUCTION: Inflammatory myofibroblastic tumors are a rare cause of primary lung tumors, most often solitary and in more than 50% of cases detected in individuals under 40 years of age. OBSERVATION: A 17-year-old patient consulted in pneumology for development of hemoptysis over a period of two weeks. Thoracic computed tomography revealed a left lower lobe cavity 24mm in diameter with bronchial fistulation and hydro-aeric level. Bronchial fibroscopy by mini-endoscope highlighted an endobronchial lesion in a subdivision of the sub-segmental posterior aspect of the left lower lobe. Paraclinical assessment highlighted a probable inflammatory myofibroblastic tumour. A surgical intervention was indicated and a lower left lobectomy performed. Histological analysis confirmed the presence of the tumour, which was resected in healthy margins by left lower lobectomy.

[Tuberculosis in general practice in Belgium : What's new?] / Tuberculose en Belgique : Quoi de neuf pour le praticien ?

Tuberculosis is still an important disease in Belgium, mainly in big agglomerations. For this reason, knowledge of this entity by a general practitioner is very important. Genetic tests able to identify the species of Mycobacterium tuberculosis have been developed in recent years, but also identification of resistance to 1st and 2nd line treatment through genetic methods has been developed. The quick availability of results of this tests compared to the standard tests is a big advantage. Treatment of drug-susceptible tuberculosis hasn't changed recently. In contrast a lot has changed in the landscape of multidrug resistant tuberculosis with the development of 2nd line drugs and shortening of treatment duration in specific cases of multidrug resistant tuberculosis.

La tuberculose reste une maladie importante en Belgique, surtout au niveau des grandes agglomérations. Il est donc toujours important qu'un praticien connaisse bien cette entité. Les évolutions récentes au niveau du diagnostic sont certainement les tests génétiques qui nous permettent de diagnostiquer l'espèce de Mycobacterium tuberculosis, mais également les éventuelles résistances au traitement de 1re et 2e ligne et ce dans un délai beaucoup moins important que les tests standards. Au niveau thérapeutique, rien n'a changé ces dernières années pour la tuberculose multisensible. Par contre, on a récemment observé de nombreuses évolut ions avec de nouveaux médicaments de 2e ligne et une réduction de la durée du traitement dans certains cas de tuberculose multirésistante.

[Atypical respiratory tract infections in adult patients in the primary care]. / Les infections broncho-pulmonaires à germes atypiques chez l'adulte : Mythe ou réalité ?

Respiratory tract infections remain one of the most frequently encountered acute illnesses in the primary care. Atypical germs along with Streptococcus pneumoniae are an important cause of community-acquired pneumonia. Most infections caused by atypical germs are mild or moderate but some of them might cause a severe disease with important morbidity and mortality. Diagnosis of community-acquired pneumonia remains a challenge in the primary care. On the other hand some of them are reported to be associated with chronic cough which is a common problem in the general practice. The aim of this mini-review is to give a short overview of some data on local prevalence, presentation and scoring systems, with stress on feasibility of current diagnostic methods in the primary care practice and therapeutic considerations for the general practitioners.

Les infections respiratoires sont la première cause de consultation en médecine générale. Le Streptococcus pneumoniae suivi par les germes atypiques sont une cause importante de pneumonies bactériennes en médecine extrahospitalière. La cause d'une pneumonie communautaire chez les patients hospitalisés est par ordre de fréquence décroissante, un organisme encore inconnu ou non détecté, des virus et enf in des bactéries1. Les germes atypiques sont généralement la cause d'infections peu sévères, mais peuvent malgré tout générer occasionnellement des infections plus sévères, parfois mortelles. Elles peuvent parfois simplement se manifester par de la toux chronique, un problème courant en première ligne. Diagnostiquer une pneumonie communautaire peut s'avérer difficile en médecine générale. Le but de cette mini-revue de littérature est de revoir la prévalence, la présentation clinique et les méthodes diagnostiques accessibles en première ligne, ainsi que les traitements à appliquer.

[Regional anesthesia: an extra-benefit for our patients]. / L'anesthésie locorégionale, un plus pour nos patients ....

Regional anesthesia is gaining popularity. It provides various benefits, including high quality postoperative analgesia. This leads to a diminished postoperative opioid consumption, less sensitization of peripheral and central neurons, and a reduced risk of persistent chronic pain. Moreover, regional blocks optimize functional recovery after surgery and improve the outcome of cancer patients who undergo surgery. They also reduce the risk of postoperative complications, especially wound complications. Also, regional blocks are frequently used in the management of chronic pain. Finally, in recent years, technological progress (such as the use of ultrasonography) has made these anesthesia techniques safer and more comfortable for the patient.

[Determining factors of walking distance during 6-minutes walk test in COPD patients]. / Déterminants de la distance parcourue et de la dyspnée lors du test de marche de six minutes chez les patients atteints de BPCO.

INTRODUCTION: In stable COPD, we studied the factors determining six-minute walking distance and dyspnea at the end of the test. METHODS: Patients were evaluated by tests of lung function, St Georges' respiratory questionnaire (SGRQ) and 6MWT with inspiratory capacity measurements (IC) and continuous oxymetry. RESULTS: Eighty-two patients (mean FEV(1): 56+19% predicted) were studied. Mean 6-minute walking distance was 477+89m, (72+14% PV). Walking distance during 6MWT (m) was correlated with FEV(1), IC/TLC ratio, TLC, pre-test IC and DLco/VA. When expressed as a percent of predicted values, walking distance was correlated with FRC, pre-test IC and SGRQ activity score. End-test dyspnea was correlated with FRC, pre-test dyspnea and SGRQ activity and total scores. CONCLUSION: The factors determining 6-minute walking distance and end-test dyspnea are complex and include both functional and non-functional factors. In COPD, 6MWT is thus an investigation that has additional integrative value.

Diagnostic bronchoscopy: state of the art.

Since the introduction of the flexible fibreoptic bronchoscope in the late 1960s there have been relatively few technological advances for three decades, aside from the development of a white light video bronchoscope with a miniature charge-coupled device built in its tip replacing the fibreoptics. White light flexible videobronchoscopy with its ancillary devices (forceps biopsy, bronchial brushing, bronchoalveolar lavage, bronchial washings and transbronchial needle aspiration) has long been the only established diagnostic bronchoscopic technique. With the advances in microtechnology over the past two decades, recent technical developments such as autofluorescence bronchoscopy and endoscopic ultrasound allow better evaluation of endobronchial, mediastinal and parenchymal lesions.

Lung volume reduction for severe emphysema: do we need a scalpel or a scope?

Resectional lung volume reduction has proven to be superior to medical treatment in reducing dyspnoea and in increasing lung function, survival and quality of life in a very well selected, low risk group of hyperinflated patients with heterogeneous emphysema predominantly in the upper lobe. Nevertheless, this intervention is hampered by an important pulmonary (30%) and cardiovascular (20%) morbidity, mainly as a result of prolonged (>7 days) air leak, and a 5% risk of death as a result of the surgical intervention. Results from ongoing randomised trials are awaited in order to determine whether less invasive, non-resectional lung volume treatment of emphysema via the bronchoscope using endobronchial valves, airway bypass stents or biological adhesives/heated water vapour will yield similar improvement with less morbidity and reduced mortality, compared with surgical resection. Furthermore, it is hoped that endoscopic lung volume reduction techniques may help patients with homogeneous emphysema currently excluded by most teams for the resectional procedure.

Guia para prática clínica: fisioterapia em pacientes com Doença Pulmonar Obstrutiva Crônica (DPOC): [review] / Clinical practice guideline for physical therapy in patients with Chronic Obstructive Pulmonary Disease (COPD): portuguese version: [review]

INTRODUÇÃO: No contexto da colaboração internacional para desenvolvimento de guias práticos (ou guidelines), a Sociedade Real Holandesa de Fisioterapia (Koninklijk Nederlands Genootschap voor Fysiotherapie, KNGF) se propôs a desenvolver um guia para esclarecimento sobre a prática clínica de Fisioterapia em pacientes com Doença Pulmonar Obstrutiva Crônica (DPOC), assim como também optou por estimular a sua tradução para outras línguas, a fim de torná-lo acessível para públicos internacionais. OBJETIVOS: O presente guia é a versão em língua portuguesa do Guia para Prática Clínica de Fisioterapia em pacientes com DPOC desenvolvido pela KNGF, que teve como objetivo descrever a Fisioterapia baseada em evidências para pacientes com DPOC que apresentam limitação da função pulmonar, da função muscular respiratória e periférica, da capacidade de exercício, da depuração mucociliar e da qualidade de vida, além de limitações em relação à atividade física na vida diária pela dispneia e/ou intolerância ao exercício. CONCLUSÃO: O guia propõe-se principalmente a prover recomendações terapêuticas práticas que auxiliem o fisioterapeuta a oferecer o melhor tratamento possível para pacientes com DPOC, consideradas as evidências científicas disponíveis na atualidade.

INTRODUCTION: In the context of international collaboration for the development of practice guidelines, the Royal Dutch Society for Physical Therapy (Koninklijk Nederlands Genootschap voor Fysiotherapie, KNGF) has developed guidelines for the clinical practice of physical therapy in patients with Chronic Obstructive Pulmonary Disease (COPD). It has also stimulated its translation into other languages to make it accessible to international audiences. OBJECTIVES: The present document brings the Portuguese version of the KNGF Clinical Practice Guidelines for physical therapy in COPD patients. Its purpose was to describe evidence-based physical therapy for COPD patients with impairments in pulmonary function, peripheral and respiratory muscle function, exercise capacity, mucus clearance and quality of life, in addition to limitations in physical activity in daily life due to dyspnea and/or exercise intolerance. CONCLUSION: The guideline provides practical and therapeutic recommendations based on currently available scientific evidence to help the physical therapist provide the best possible treatment to COPD patients.

A clinical practice guideline for physiotherapists treating patients with chronic obstructive pulmonary disease based on a systematic review of available evidence.

PURPOSE: Update of a clinical practice guideline for the physiotherapy management of patients with chronic obstructive pulmonary disease supporting the clinical decision-making process. METHODS: A systematic computerized literature search was performed on different modalities for improving physical exercise capacity, reducing exertional dyspnoea, improving airway clearance and encouraging changes in physical activity behaviour. Methodological quality was scored with the PEDro Scale. Scientific conclusions were graded according to the criteria of the; Dutch Evidence Based Guideline Development Platform'. These, together with practical considerations, were used to formulate recommendations for clinical practice. RESULTS: A total of 103 studies were included in the systematic review, consisting of five meta-analyses of randomized controlled trials, 84 randomized controlled trials and 14 uncontrolled studies. Twenty scientific conclusions supported six recommendations on physical exercise training. Nineteen scientific conclusions supported eight recommendations on interventions for reducing dyspnoea. Five scientific conclusions supported seven recommendations concerning treatment modalities to improve mucus clearance, and two scientific conclusions supported two recommendations on strategies for encouraging permanent changes in physical activity behaviour. CONCLUSIONS: Strong recommendations support the use of physical exercise training to improve health-related quality of life and functional exercise capacity. Future research should investigate whether additional interventions for reducing exertional dyspnoea have a place as adjuncts to physical exercise training in selected patients. In addition, treatment of impaired mucus clearance, especially during acute exacerbations, requires further research. With the advance of new technologies for objective measurements of physical activities in daily life more research is needed concerning interventions to initiate and maintain physical activity behaviour change during and after supervised physical exercise training programmes.

Evolution of microRNA expression during human bronchial squamous carcinogenesis.

MicroRNAs, negative post-transcriptional regulators of gene expression, are involved in cancer. Their role in early bronchial carcinogenesis was analysed in 60 biopsies obtained by fluorescence bronchoscopy (six per stage: normal tissue of nonsmokers, normal normofluorescent and hypofluorescent bronchial tissue of smokers, hyperplasia, metaplasia, mild, moderate and severe dysplasia, in situ carcinoma and invasive squamous cell carcinoma (SQCC)). In total, 69 microRNAs were found to be differentially expressed in the course of bronchial carcinogenesis. Among them, some microRNAs showed a linear evolution of their expression level, such as miR-32 and miR-34c, whose expression progressively decreased from normal bronchial tissues of nonsmokers to SQCC. Others behaved differently at successive stages, such as miR-142-3p or miR-9, or are only altered from a specific stage, such as miR-199a or miR-139. MicroRNAs globally followed a two-step evolution, first decreasing (a reverse of their increase during embryogenesis) during the earliest morphological modifications of bronchial epithelium, and thereafter increasing at later stages of lung carcinogenesis. Moreover, microRNA expression was very efficient for the prediction of the histological classification between low- and high-grade lesions and between in situ and invasive carcinoma. The present data show, for the first time, that microRNAs are involved in bronchial carcinogenesis from the very early steps of this process and, thus, could provide tools for early detection of lung cancer.

The role of NPM, p14arf and MDM2 in precursors of bronchial squamous cell carcinoma.

Murine double minute clone 2 (MDM2), p14 alternate reading frame (p14arf), and nucleophosmin (NPM) regulate p53 activity. A total of 200 biopsies, including normal bronchial, pre-invasive and invasive tissues, were examined for changes in NPM, p14arf, MDM2 and p53 expression patterns by immunohistochemistry and immunofluorescence with confocal microscopy. NPM and p14arf displayed a diffuse nuclear staining in most normal bronchial tissue. The fraction of biopsies displaying an increased MDM2 staining or a nucleolar relocalisation of NPM increased at mild and moderate dysplasia, respectively. Two different modifications occurred in p14arf expression, i.e. its loss or its nucleolar relocalisation, both increasing at severe dysplasia and both being associated with high MDM2 expression. In addition, the nucleolar relocalisation of p14arf was associated with that of NPM. Immunofluorescence staining indicated that NPM and p14arf either co-localised in the nucleoplasm or in the nucleoli, before and as a result of severe dysplasia, respectively. MDM2 was not detected in the nucleoli. Thus, changes occur in murine double minute clone 2, p14 alternate reading frame and nucleophosmin level of expression and/or cellular distribution during early steps of lung carcinogenesis. Their relative localisation as determined by immunofluorescence, supports the hypothesis that p14 alternate reading frame nucleolar relocalisation impairs p14 alternate reading frame-murine double minute clone 2 complex formation and that nucleophosmin might sequester p14 alternate reading frame. The demonstration of this hypothesis requires further functional studies.

Chemotherapy improves low performance status lung cancer patients.

The aim of the present study was to determine the potential benefit of conventional cisplatin-based chemotherapy on patients with advanced nonsmall cell lung cancer (NSCLC) and poor performance status (PS), defined as 60-70 on the Karnofsky scale. Retrospective analysis was carried out of a randomised trial performed in advanced NSCLC where 485 patients received three courses of gemcitabine+ifosfamide+cisplatin induction chemotherapy. Of the patients, 80% had good PS (Karnofsky 80-100) and 20% poor PS. Response rates were 38 and 28%, respectively. Clinical improvement, defined as achieving a good PS during chemotherapy, was observed overall in 25% of the poor PS patients, with rates of 38, 20 and 14%, respectively, in case of response, no change and progression. PS improved more quickly in the responders. Survival of patients with poor PS was significantly worse, but survival of responders was similar, irrespective of the initial poor or good PS. Although nonfatal toxicity was almost similar, there were more toxic deaths (including vascular and cardiac fatalities) in the poor PS patients (9.2 versus 2.1%). In conclusion, combination chemotherapy is associated with clinical improvement in a substantial number of patients with advanced nonsmall cell lung cancer of poor performance status.

Second-line paclitaxel in non-small cell lung cancer initially treated with cisplatin: a study by the European Lung Cancer Working Party.

In the context of a phase III trial comparing in advanced non-small cell lung cancer (NSCLC) sequential to conventional administration of cisplatin-based chemotherapy and paclitaxel, we evaluated the activity of paclitaxel as second-line chemotherapy and investigated any relation of its efficacy with the type of failure after cisplatin. Patients received three courses of induction GIP (gemcitabine, ifosfamide, cisplatin). Non-progressing patients were randomised between three further courses of GIP or three courses of paclitaxel. Second-line paclitaxel was given to patients with primary failure (PF) to GIP and to those progressing after randomisation to further GIP (secondary failure or SF). One hundred sixty patients received second-line paclitaxel. Response rates were 7.7% for PF and 11.6% for SF (P=0.42). Median survival times (calculated from paclitaxel start) were 4.1 and 7.1 months for PF and SF (P=0.002). In multivariate analysis, three variables were independently associated with better survival: SF (hazard ratio (HR)=1.55, 95% confidence interval (CI) 1.08-2.22; P=0.02), normal haemoglobin level (HR=1.56, 95% CI 1.08-2.26; P=0.02) and minimal weight loss (HR=1.79, 95% CI 1.26-2.55; P=0.001). Paclitaxel in NSCLC patients, whether given for primary or for SF after cisplatin-based chemotherapy, demonstrates activity similar to other drugs considered active as second-line therapy.

A phase III randomised trial comparing sequential chemotherapy using cisplatin-based regimen and paclitaxel to cisplatin-based chemotherapy alone in advanced non-small-cell lung cancer.

BACKGROUND: The purpose of this study is to determine whether in advanced non-small-cell lung cancer (NSCLC), the sequential administration of cisplatin-based chemotherapy and paclitaxel (Taxol) is superior to a cisplatin-based chemotherapy, followed by paclitaxel as salvage treatment. PATIENTS AND METHODS: A total of 485 chemotherapy naive patients with advanced NSCLC were treated with three courses of GIP (gemcitibine + ifosfamide + cisplatin), consisting of cisplatin 50 mg/m(2) on day 1, ifosfamide 3 g/m(2) on day 1 and gemcitabine 1 g/m(2) on days 1 and 8. Patients with nonprogressive disease were then randomised to further similar courses of GIP or courses of paclitaxel (225 mg/m(2) over 3 h every 3 weeks). RESULTS: Objective response or nonprogression after induction GIP occurred in 174 and 115 patients, respectively. After randomisation, there were 140 patients in the GIP arm and 141 in the paclitaxel arm. In terms of postrandomisation survival, there was no statistically significant difference (P = 0.17) between the two arms. Median times were 9.7 [95% confidence interval (CI) 7.8-11.6] and 11.9 (95% CI 9.4-14.3) months for paclitaxel and GIP, respectively. Multivariate analysis demonstrated that sex and haemoglobin were independent prognostic factors. After adjustment for these factors, the observed hazard ratio was 0.81 (95% CI 0.63-1.04) in favour of GIP (P = 0.10). Toxicity was tolerable; there was a significantly higher rate of grades III/IV thrombocytopenia with GIP and more alopecia with paclitaxel. CONCLUSION: Sequential chemotherapy using cisplatin-based regimen followed by paclitaxel does not result in better outcome than cisplatin-based chemotherapy using taxane as salvage treatment.