[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.

[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.

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.

[New diagnostic techniques in bronchial endoscopy]. / Les nouvelles techniques diagnostiques endoscopiques.

The diagnostic work-up of peripheral lung lesions or nodules remains controversial. Endobronchial ultrasound (EBUS) or electromagnetic navigation with guided sampling have increased the yield of conventional flexible bronchoscopy and results seem to be independent of lesion size. In addition, these techniques may be combined with further improvement in yield that then compares with transthoracic needle aspiration. Mediastinal lymph node tissue diagnosis is often required in the staging of lung cancer and real-time guided EBUS or EUS (endoscopic ultrasound, transoesophageal ultrasound) sampling show excellent results without significant complication. These combined techniques may also be complementary and allow complete staging of the mediastinum that will probably reduce the need for surgical staging.

Prognostic role of thyroid transcription factor-1 in stage III non-small cell lung cancer.

UNLABELLED: Stage III NSCLC represents a heterogeneous group and the ISS remains unsatisfactory in term of prognosis prediction. The aim of the present study was to determine the role of TTF-1 as prognostic factor in stage III NSCLC in addition to other known clinical factors. All stage III NSCLC patients treated in our hospital were retrieved and searched for biopsy specimens. TTF-1 was assessed by immunohistochemistry (Novocastra SPT24). Between 01/1987 and 07/2003, 108 assessable stage III NSCLC patients were included in the study. Their principal characteristics were: median age 64 years (range 37-83), male/female 81/27, squamous/non squamous 52/56, IIIA/IIIB 44/64, median Karnofsky PS 80 (range 20-100). Forty-four patients were positive for TTF-1 (squamous 25.0% versus non-squamous 55.4%). In multivariate analysis, only three factors were statistically significantly associated with better survival: good PS, surgery and creatinine level. CONCLUSION: In stage III NSCLC patients, good PS, resectability and low creatinine level but not TTF-1 are prognostic factors for survival.

EGFR, c-erbB-2 and ki-67 in NSCLC and preneoplastic bronchial lesions.

BACKGROUND: The relationships between EGF-R and c-erbB-2 with other factors involved in tumour regulation are not well understood. The aim of this study was to correlate the expression of these markers with tumour proliferation. MATERIALS AND METHODS: The presence of EGF-R, c-erbB-2 and Ki-67 was evaluated by immunohistochemistry in non-small cell lung cancer (NSCLC) and preneoplastic lesions. RESULTS: Forty-two percent of the tumours were positive for EGF-R, 22% for c-erbB-2 and 97% for Ki-67. No statistically significant correlation was found between EGF-R and Ki-67, EGF-R and c-erbB-2 or between c-erbB-2 and Ki-67. With regards to Ki-67, a significant difference in survival was noted in favour of patients who did not express the marker. In preneoplastic lesions, most of the low-grade lesions showed neither EGF-R nor Ki-67 staining. In contrast, most of the high-grade lesions stained positively for these proteins. CONCLUSION: EGF-R and c-erbB-2 do not seem to be correlated with Ki-67 in NSCLC.

[Endobronchial ultrasound and PET positive mediastinal lymph nodes]. / Echographie endobronchique et ganglions TEP positifs dans le cancer broncho-pulmonaire.

INTRODUCTION: In bronchial carcinoma when positron emission tomography with 18-fluorodeoxyglucose (FDG-PET) shows increased emission in the mediastinal lymph nodes, confirmation by tissue biopsy is necessary. In this particular situation we have evaluated the use of real time lymph node aspiration under endobronchial ultrasound control. METHODS: Consecutive patients referred for staging and/or diagnosis of PET positive mediastinal nodes in the setting of suspected or confirmed bronchial carcinoma were included. The results of lymph node aspiration, performed under local anaesthesia in out-patients, were collected and if non-diagnostic surgical exploration was performed. RESULTS: 20 patients were studied between December 2004 and September 2005. The average number of ultrasound guided needle aspirations per patient was 4.8 +/- 1.2. Cytological or histological confirmation of malignancy was obtained by needle biopsy in 12 patients. The 8 negative cases were confirmed by surgical biopsy. In this preliminary series the sensitivity, specificity and negative predictive value of ultrasound guided aspiration of PET positive nodes was 100%. CONCLUSION: Endobronchial ultrasound with needle aspiration should be considered a primary method of investigation of PET positive mediastinal lymph nodes.

Phase III randomized trial comparing cisplatin and carboplatin with or without ifosfamide in patients with advanced non-small-cell lung cancer. European Lung Cancer Working Party.

PURPOSE: A phase III randomized trial in patients with advanced non-small-cell lung cancer (NSCLC) was performed to determine if the addition of ifosfamide to moderate-dose cisplatin and carboplatin improved response rate (primary end point) and survival. PATIENTS AND METHODS: A total of 529 patients were randomized to receive a combination of moderate-dose carboplatin (200 mg/m2 intravenously [i.v.] on day 1) and cisplatin (30 mg/m2 i.v. on days 2 and 3) with (CCI arm) or without (CC arm) ifosfamide (1.5 g/m2 i.v. on days 1 to 3). There were 248 eligible patients on the CC arm and 257 on the CCI arm, with 220 and 238 patients assessable for response, respectively. All but 23 had stage IV disease with pleural effusion. RESULTS: There was a 16% objective response (OR) rate to CC and a 31% OR rate to CCI. That observed difference was highly statistically significant (P < 0.001). Duration of response and survival were not statistically different between arms. The CCI regimen was associated with significantly more acute toxicities: emesis, alopecia, leukopenia, and thrombocytopenia. The frequency of chronic renal, auditive, and peripheral neurologic toxicity was low in both arms (4.6% and 6.6%, respectively, after six courses of chemotherapy). The relative dose-intensity (RDI) of the CCI arm was significantly lower than that of the CC arm. CONCLUSION: The addition of ifosfamide to moderate-dose cisplatin and carboplatin significantly improves the antitumoral response rate, but has no apparent effect an survival in advanced NSCLC.

Mitomycin, ifosfamide, cisplatin for non-small cell lung cancer: an implementation study.

BACKGROUND: The MIP regimen (mitomycin, ifosfamide, cisplatin) demonstrated its effectiveness as first-line chemotherapy in phase II and III trials in NSCLC. We aimed to determine whether these results could be confirmed in a hospital population. METHODS: Between 1987 and 2004, 204 patients with NSCLC received MIP in our institution. Patients treated in and off trials received the same combination of cisplatin (50 mg/m2), ifosfamide (3 g/m2) and mitomycin C (6 mg/m2) every three weeks and were staged and followed in a similar way. RESULTS: Response rates for patients treated in or outside trials were 36.8% and 40.7%, respectively. After multiple logistic regressions, the only statistically significant factor predicting objective response was stage. The median survival time was 54.6 and 43.7 weeks respectively for patients treated in and outside trials. In multivariate analysis, four factors were statistically significantly associated with better survival: good performance status (p = 0.003), normal LDH value (p < 0.001), early stage (p = 0.01) and active smoking (p = 0.03). CONCLUSION: Participation in a clinical trial was not associated with a significant difference in efficacy. This implementation study thus confirms the activity of the MIP regimen when used in the routine management of patients with NSCLC.

Acute respiratory failure from tracheopathia osteoplastica.

Tracheopathia osteoplastica is a benign cartilaginous and osseous metaplasia of the laryngo-tracheobronchial tree diagnosed more commonly in adults over 50 years of age. We report here the case of a 54-year-old man who underwent thyroidectomy for multinodular goiter. Immediately after an uneventful surgery, he developed an acute respiratory failure with radiologic picture of Adult Respiratory Distress Syndrome. Mechanical ventilation was set up again, bronchoscopy with biopsy disclosed a massive tracheobronchial haemorrhage from a tracheopathia osteoplastica. Supportive treatment was successfully provided and the patient resumed to a normal life 14 days after the operation.

Acute respiratory failure from tracheopathia osteoplastica.

Tracheopathia osteoplastica is a benign cartilaginous and osseous metaplasia of the laryngo-tracheobronchial tree diagnosed more commonly in adults over 50 years of age. We report here the case of a 54-year-old man who underwent thyroidectomy for multinodular goiter. Immediately after an uneventful surgery, he developed an acute respiratory failure with radiologic picture of Adult Respiratory Distress Syndrome. Mechanical ventilation was set up again, bronchoscopy with biopsy disclosed a massive tracheobronchial haemorrhage from a tracheopathia osteoplastica. Supportive treatment was successfully provided and the patient resumed to a normal life 14 days after the operation.

[Bronchoscopic early detection of lung cancer]. / Le diagnostic précoce endoscopique du cancer broncho-pulmonaire.

The centrally located lung cancer mainly corresponds to squamous cell carcinoma localized in the large airways. In this paper, tools that are used for the detection of this cancer at the earliest stages are reviewed. Fluorescence bronchoscopy is the latest major advance for the early detection of this cancer.

[Manual abdominal compression for the detection of expiratory flow limitation]. / La compression abdominale manuelle dans la détection de la limitation du débit expiratoire.

INTRODUCTION: Expiratory flow limitation (EFL) is a characteristic feature of chronic obstructive pulmonary disease (COPD) and leads to dynamic hyperinflation (DH) which is a major source of dyspnoea, particularly during exercise. STATE OF THE ART: A new technique for the detection of EFL, based on manual compression of the abdomen (MCA), was assessed both in normal subjects and patients with COPD. MCA was always associated with a moderate increase in pleural pressure and allowed the detection of EFL in a reproducible manner, in both the seated and supine postures. The technique was well tolerated. It was also a reliable method for the detection of EFL during exercise since EFL detection was effectively associated with the development of DH. Finally, MCA was also compared to NEP in patients with obstructive sleep apnoea syndrome (OSAS) and in these patients, MCA invariably increased expiratory flow whereas the NEP method produced flow limitation in some cases because of upper airway collapse. PERSPECTIVES: EFL detection with MCA may be clinically useful since EFL is a determinant of dyspnoea, affects ventilatory response to exercise as well as maximum exercise capacity. CONCLUSIONS: MCA is a reliable technique for the detection of EFL in different positions, during resting breathing or exercise, requiring neither special equipment nor patient cooperation.

A comparison of methods of calculation for estimating carboplatin AUC with a retrospective pharmacokinetic-pharmacodynamic analysis in patients with advanced non-small cell lung cancer. European Lung Cancer Working Party.

We retrospectively analysed the data obtained in a large randomised trial performed in 505 eligible patients with advanced non-small cell lung cancer. Its purpose had been to compare a combination of carboplatin (200 mg/m2) and cisplatin (60 mg/m2) with or without the addition of ifosfamide. The present retrospective analysis assessed two ways of dosing carboplatin: according to body surface area (mg/m2) or to the estimated targeted area under the concentration versus time curve (AUC). Two different methods were used in the latter calculation: the Calvert formula using the Cockroft approximation to evaluate the glomerular filtration rate and the Chatelut equation. There was an excellent linear correlation between them. With the Chatelut method, the calculated administered AUC were lower. Whichever method was used, carboplatin AUC was not significantly associated with antitumour response rate nor patient survival. A statistically significant increase in haematological toxicity, mainly thrombopenia, was observed with an increase in the AUC. This effect was observed whatever AUC variable was considered, i.e. total dosage at course one, total dosage during the first three chemotherapy courses or dose intensity during the first three courses. The effect remained highly significant after adjustment for treatment arm. We conclude that for a moderate carboplatin dose in non-small cell lung cancer, the therapeutic index could be improved if dosage is calculated according to the AUC.

Synchronous roentgenographically occult lung carcinoma in patients with resectable primary lung cancer.

OBJECTIVE: To assess the prevalence of synchronous roentgenographically occult lung carcinoma (ROLC) in patients with resectable roentgenographically visible lung cancer (RVLC). METHODS: Patients undergoing surgery for RVLC in the same University Hospital were prospectively evaluated before surgery by fluorescence bronchoscopy under local anesthesia to detect synchronous ROLC. All abnormal areas, with the exception of the RVLC, had biopsies made. RESULTS: From June 1996 to January 1999, 43 patients (male/female ratio: 1.7/1.0) were evaluated before lobectomy (n = 34) or pneumonectomy (n = 10) for 44 primary RVLC. There were 10 T1N0, 19 T2N0, 1 T1N1, 9 T2N1, 1 T3N0, 3 T1N2, and 1 T3N1 lesions. The histologic type was mainly squamous carcinoma (n = 21) and adenocarcinoma (n = 14). All but two patients were smokers or ex-smokers (mean +/- SD, 48 +/- 28 pack-years). A total of 177 endobronchial biopsies were performed (4.1 +/- 2.5); 8 were too small to be informative, 43 showed non-preneoplastic alterations, and 50 were normal. There were 7 basal cell hyperplasias, 56 metaplasias, 9 dysplasias, and 4 carcinomas in situ (CIS). All the dysplasias and CIS lesions were observed in eight subjects. The synchronous CIS were treated by surgery (n = 1) or localized therapeutic modalities (n = 3). CONCLUSIONS: The high prevalence of synchronous early lung cancers (9.3%) as well as metaplasia and dysplasia in this series of patients with resectable RVLC suggests that fluorescence bronchoscopy may be a useful adjunct in the preoperative evaluation of lung cancer.