[Central nervous system tuberculosis : don't miss the diagnosis !] / Errance diagnostique dans un cas de tuberculose du système nerveux central Nebie A (1), Ali D (1), Bosquee L (2), Gorur Y (3), Cardos B (4).

We are presented a 35-year-old patient with no previous relevant medical history who was admitted to the emergency department for fever, altered mental status and diffuse abdominal pain. Initial evaluation failed to the demonstrated the presence of thoracic or abdominal deep infection. The clinical course was marked by a deterioration of the neurological condition. The cerebral MRI showed diffuse and extensive involvement of the brainstem and cerebellar hemispheres associated with hydrocephalus consistent with tuberculous meningoencephalitis. Antituberculous therapy was started with some delay but no clinical improvement was achieved and the patient died.

Une patiente âgée de 35 ans, sans antécédents médicaux particuliers, est admise au service des urgences pour fièvre accompagnée d'un syndrome confusionnel et de douleurs abdominales diffuses. La prise en charge initiale ne permet pas de mettre en évidence une infection profonde au niveau thoracique et abdominal. L'évolution clinique est marquée par une détérioration de son état neurocognitif. L'IRM cérébrale montre une atteinte diffuse et étendue des hémisphères cérébraux, du tronc cérébral et du cervelet, associée à une hydrocéphalie, liée à une probable méningo-encéphalite tuberculeuse. Un traitement antituberculeux est instauré avec un certain délai, mais aucune amélioration clinique n'est observée et la patiente finit par décéder.

[Hypoxemic measles pneumonitis in an immunocompetent adult]. / Le cas clinique du mois Pneumopathie rougeoleuse hypoxémiante chez un adulte immunocompétent.

Measles is a highly contagious viral disease and one of the biggest causes of morbidity and mortality in the world. Transmission occurs from person to person through direct contact or by aerosolization of pharyngeal secretions. It can be responsible for severe respiratory and neurological complications. The diagnosis is clinical, confirmed by serology, PCR or culture of the measles virus. Treatment is symptomatic and prevention is based on a well conducted vaccination. In severe cases, the use of vitamin A is recommended by the World Health Organization, at least in chidren. Antivirals (ribavirin) have not been shown to be effective in clinical practice. We present a severe respiratory form of measles, affecting a young immunocompetent adult.

La rougeole est une pathologie virale hautement contagieuse et l'une des plus grandes causes de morbidité et de mortalité dans le monde. La transmission se fait de personne à personne, par contact direct ou par aérosolisation des sécrétions pharyngées. Elle peut être responsable de complications graves respiratoires et neurologiques. Le diagnostic est clinique, affirmé par les sérologies, PCR ou culture du virus de la rougeole. Le traitement est symptomatique et la prévention repose sur une vaccination bien conduite. Dans les cas sévères, l'utilisation de vitamine A est préconisée par l'Organisation Mondiale de la Santé, au moins chez les enfants. Les antiviraux (ribavirine) n'ont pas démontré d'efficacité en pratique clinique. Nous présentons une forme respiratoire sévère de rougeole, touchant un jeune adulte immunocompétent.

[Mycobacterium kansasii lung infection]. / LE CAS CLINIQUE DU MOIS. Infection pulmonaire à Mycobacterium kansasii.

The incidence of non tuberculosis mycobacterial (NTM) pulmonary diseases is increasing. Patients with NTM disease usually suffer prolonged periods of clinical illness prior to diagnosis. An etiological treatment, initiated by a well informed clinician and based on presumptive evidence, can be successful in a significant proportion of cases.

[The challenge of local control in unresectable locally advanced non-small cell lung cancer]. / Le défi du contrôle local dans le cancer pulmonaire, non à petites cellules, localement avancé, non opérable.

Non-small cell lung cancer (NSCLC) is common. Approximately one out of every five patients with NSCLC has locally advanced disease that is surgically unresectable. For these patients, the disease has a poor prognosis characterized by a high rate of local disease progression or recurrence despite attempts at chemo- and radiation therapy. The purpose of this review is to describe the heterogeneity of this group of patients, to clarify the terms of the combination of chemotherapy and radiotherapy and to clarify the efficacy of modern radiotherapy techniques to increase local control.

[Clinical case of the month. A patient with advanced non-small-cell lung cancer presenting with an exceptional response to targeted therapies]. / Le cas clinique du mois. Cancer bronchique avancé non à petites cellules avec réponse exceptionnelle aux thérapies ciblées.

Advanced non-small-cell lung cancers are diseases of late diagnosis with bad prognosis. Conventional chemotherapies are not very efficient. Over the last years, many research works have been performed in this way to improve prognosis. Targeted therapies seem promising. They were notably developed against epithelial growth factor receptors and tumoral angiogenesis. We report here the clinical history of a patient with an advanced non-small-cell lung cancer presenting an exceptional response to small-molecule tyrosine kinase inhibitors.

[Organizing pneumonia: three case reports]. / Pneumopathies organisées: à propos de 3 cas.

Infiltrative lung lesions are not always linked to infectious processes or cancers. An interesting entity, the OP (Organizing Pneumonia) or COP (Cryptogenic Organizing Pneumonia)--formerly BOOP (Bronchiolitis Obliterans Organizing Pneumonia)--is discussed through observations repor. ted in this article. We provide some keys to allow the astute observer to target this often curable disease.

[Paraneoplastic endocrine syndromes: diagnosis and management]. / Syndromes paranéoplasiques endocriniens: diagnostic et prise en charge.

Paraneoplastic endocrine syndromes define a group of secondary signs and symptoms associated to a neoplasia, independently from the location of the primary tumor or its metastases. Paraneoplastic or ectopic endocrine syndromes usually result from aberrant hormone precursors or hormone-like substances by tumours. Knowledge of paraneoplastic endocrine complications is important both for the early diagnosis of neoplasia and the prognosis of the patient. In this review we discuss almost all reported paraneoplastic endocrine syndromes. We analyze their prevalence, etiology, laboratory diagnosis and treatment.

[Lung cancer. Epidemiology and etiologic factors]. / Le cancer du poumon. Epidémiologie et facteurs étiologiques.

Lung cancer is the most frequent cause of death by cancer worldwide. Despite improvements in the treatment the vital prognosis remains poor with an estimated 5-year survival rate of 15 % all stages together. Even if some environmental exposure may favour apparition of the disease, tobacco smoking is by far the greatest risk factor for developing lung cancer. Recent progresses have been made on the identification of cellular mechanisms and genetic abnormalities that make the patients more prone to develop lung cancer.

[Update in treatment of non small cell lung cancer]. / Prise en charge du cancer pulmonaire non à petites cellules.

Surgery, chemotherapy, radiotherapy and "biological" treatment are differently used in the treatment of non small cell lung cancer. Surgery is the cornerstone of the stages I-II treatment; chemotherapy is dominant in the treatment of metastatic stage, but is more and more used in earlier stages. A large discussion is still open for advanced non metastatic stages, even if the association of the 3 major modalities is extensively studied. We discuss our position in this setting.

[Therapeutic update in respiratory medicine]. / Actualités thérapeutiques en pneumologie.

We review what we think to be the major advances in the field of respiratory medicine over the last ten years. We concentrate here on four major diseases i.e. asthma, chronic obstructive pulmonary disease (COPD), lung cancer and chronic respiratory insufficiency due to restrictive disorders. Therapeutic advances are based either on new drugs or on new disease management concepts and, in some cases, on new medical devices. These advances have allowed a reduction in mortality and morbidity in aforementioned diseases.

Gefitinib monotherapy in advanced nonsmall cell lung cancer: a large Western community implementation study.

Epidermal growth factor receptor tyrosine kinase inhibitors represent a new treatment option for patients with advanced nonsmall cell lung cancer (NSCLC). This retrospective study examined to what extent previous clinical trial experience matches large-scale Western community implementation of this treatment. In the Belgian expanded access programme, the data from 513 patients with advanced or metastatic NSCLC, not suitable for further chemotherapy and receiving oral gefitinib 250 mg.day(-1) until disease progression, death or unacceptable toxicity, were analysed. The median (range) duration of gefitinib treatment was 2.3 months (0.0-32.7). Its use was predominantly in second- or third-line treatment. The overall response and disease control rates were 8.9 and 41.2%, respectively. In univariate analysis, response was more common in females and never-smokers. In multivariate analysis, female sex was the only significant predictive factor (odds ratio (OR) (95% confidence interval (CI)) 0.329 (0.129-0.839)). Symptom improvement was reported in 108 patients of whom 32 (29.6%) had an objective response, 66 (61.1%) experienced disease stabilisation and 10 (9.3%) progressed. Gefitinib was well tolerated; only 7.8% of the patients reported grade 3 or 4 toxicity. The overall median survival was 4.7 months, with a 1-yr survival rate of 21%. Survival was strongly influenced by a better performance status (PS) (good PS: hazard ratio (HR) (95%CI) 0.110 (0.077-0.157)) and adenocarcinoma with bronchioloalveolar carcinoma features histology (HR (95%CI) 0.483 (0.279-0.834)). In conclusion, the activity of gefitinib was confirmed in the present large Western community implementation study. Response, present in a small subgroup, led to a rewarding survival and could be predicted by sex only. Baseline performance status and adenocarcinoma with bronchioloalveolar carcinoma features histology were significant factors for survival.

[Diabetes insipidus in a patient with small-cell lung cancer: a paradox?]. / Diabète insipide dans le cadre d'un carcinome pulmonaire à petites cellules: un paradoxe?

We observed oat-cell lung carcinoma in a man who presented with diabetes insipidus. The chest radiograph showed a suspect nodule within a context of major nicotine addiction. Histopathological examination of the transbronchial biopsy confirmed the diagnosis of oat-cell carcinoma. Brain CT revealed metastasis to the pituitary gland and the pituitary stalk. Vasopressin was undetectable. This case illustrates an uncommon clinical presentation of small-cell lung carcinoma. Oat-cell carcinoma can modify osmoregulation in two different ways. Only sporadic cases of neurogenic diabetes insipidus due to the primary involvement of small-cell lung carcinoma have been reported. More often, this type of lung tumor is associated with inappropriate antidiuretic hormone secretion.

[Clinical case of the month. Pulmonary toxicity due to gemcitabine for NSCLC with brain metastasis]. / Toxicité pulmonaire de la gemcitabine dans le cadre d'un CPNPC avec carcinomatose cérébrale.

Gemcitabine pulmonary toxicity is rare and represents a difficult diagnosis. A 61 year old female treated with gemcitabine for a metastatic non-small cell lung cancer (NSCLC) developed during the fifth chemotherapy cycle an acute respiratory distress syndrome with fever, tachypnea, marked hypoxemia and a diffuse interstitial-alveolar infiltrate on chest radiograph. No infectious or opportunistic etiology or cardiovascular disease was demonstrated. Withdrawal of gemcitabine and administration of corticosteroids led to symptomatic improvement. This acute pneumonitis was likely drug induced.

Increased TGFbeta1 plasma level in patients with lung cancer: potential mechanisms.

BACKGROUND: Plasma transforming growth factor beta1 (TGFbeta1) levels are elevated in patients with lung cancer. As TGFbeta1 is mainly found in platelets and as nonmalignant pulmonary diseases (NMPD) are frequently associated with lung cancer, we investigated the potential contribution of platelet degranulation and/or of a concomitant NMPD to the increased plasma levels of TGFbeta1 reported in patients with lung cancer. MATERIALS AND METHODS: Blood samples were collected in duplicate from 30 healthy subjects, 14 patients suffering from NMPD and 37 patients with lung cancer. The platelet count was determined and the samples were processed to obtain plasma. One sample was collected in EDTA (EDTA plasma) and the other in a mixture inhibiting platelet degranulation (PIM plasma). TGFbeta1 concentrations and beta-thromboglobulin (betaTG) levels, an index of platelet degranulation, were measured in both plasma samples. RESULTS: TGFbeta1 and betaTG plasma levels measured in PIM plasma were lower than those obtained in EDTA plasma. With respect to PIM plasma, both TGFbeta1 and betaTG levels were higher in patients with lung cancer than those with NMPD and in healthy individuals. In patients with NMPD, only TGFbeta1 levels were increased as compared to healthy controls, betaTG levels being similar. CONCLUSION: Methods for collecting and processing blood samples are critical in determining reliable circulating TGFbeta1 levels. Increased TGFbeta1 plasma levels observed in patients with lung cancer are related, at least partly, to concomitant NMPD and also to platelet degranulation as proved by increased betaTG levels.

Gemcitabine plus etoposide in chemonaive extensive disease small-cell lung cancer: a multi-centre phase II study.

BACKGROUND: Both gemcitabine and etoposide are active in the treatment of small-cell lung cancer (SCLC), and are characterised by mild toxicity profiles. The combination of both drugs was found to be feasible and active in a phase I dose-finding study in solid tumours. Therefore, a phase II trial was initiated to examine the activity and toxicity of this schedule in extensive disease SCLC. PATIENTS AND METHODS: Forty-two chemo-naïve extensive disease SCLC patients were enrolled to receive gemcitabine 1000 mg/m2, days 1, 8 and 15, and etoposide 80 mg/m2, days 8, 9 and 10 of a 28-day cycle. RESULTS: Thirty-seven patients were evaluable for efficacy (five received less than one cycle). No complete responses were observed, but partial responses were seen in 17 patients, yielding an overall response rate of 46%. The median duration of response was 5.8 months. Disease stabilisation was obtained in another 10 patients (27%). The median survival of the 37 protocol-qualified patients was 10.5 months (95% confidence interval (CI): 7.5-12.0). The levels of WHO grade 3 and 4 toxicities were low and clinically manageable. CONCLUSION: In comparison with standard platinum-based regimens, this combination of gemcitabine and etoposide resulted in a somewhat lower response rate, but a similar median survival time. Haematological toxicity was more pronounced than expected from the toxicity data of each agent individually. However, because of its mild non-haematological toxicity, and its ability to be administered in an outpatient setting, this combination provides a reasonable palliative option for patients with extensive disease SCLC.

Phase II study of docetaxel in the treatment of patients with advanced non-small cell lung cancer in routine daily practice.

The purpose of this study was to evaluate the efficacy and safety of docetaxel as first- and second-line chemotherapy for advanced non-small cell lung cancer (NSCLC) under routine clinical conditions. Two hundred and three patients with advanced NSCLC received docetaxel 100 mg/m2 (1-h intravenous infusion) every 3 weeks, with oral corticosteroid pre-medication, of whom 173 were eligible. Median age was 60 (29-78) years and median Karnofsky performance status was 80% (60-100). A total of 77% of patients had metastatic disease, 33% had bone metastases and 18% had liver metastases. The treatment was second-line or more for 72 patients (35%). Overall response rates in the eligible population were 19.7% [95% CI, 12.5-23.0] for both treatments, 22.6% for first-line treatment and 13.8% for second-line treatment. Median survival was 8.3 months and 1-year survival was 35% for the overall population (8.7 months and 38%, respectively, for patients receiving first-line treatment and 7.2 months and 27%, respectively, for patients receiving second-line treatment). Neutropenia, grade 3 and 4, occurred in 57% of the cycles and 5% of patients experienced febrile neutropenia. Alopecia (62% of patients), neuro-sensory symptoms (32%), asthenia (28%), diarrhea (22%), nausea (22%) and nail disorders (20%) were the most common non-hematological adverse effects. A total of 33% of patients suffered fluid retention, despite the use of corticosteroid pre-medication, but this was only severe in 1.5% of patients. It was possible to confirm the efficacy of docetaxel as a single agent for first- and second-line chemotherapy in a large patient population treated in a community setting.

Multiple courses of high-dose ifosfamide, carboplatin, and etoposide with peripheral-blood progenitor cells and filgrastim for small-cell lung cancer: A feasibility study by the European Group for Blood and Marrow Transplantation.

PURPOSE: To determine the feasibility and safety of multiple sequential courses of high-dose chemotherapy and peripheral-blood progenitor cells (PBPCs) administered in a multicenter setting to patients with small-cell lung cancer. PATIENTS AND METHODS: Sixty-nine patients (limited disease, n = 30; extensive disease, n = 39) treated at 15 European centers were scheduled to receive three courses of high-dose chemotherapy with ifosfamide 10 g/m(2), carboplatin 1200 mg/m(2), and etoposide 1200 mg/m(2) (ICE) divided over 4 days at 28-day intervals. PBPCs were harvested before treatment and mobilized with epirubicin 150 mg/m(2) administered via an intravenous bolus divided over 2 days and filgrastim 5 microg/kg/d administered subcutaneously. RESULTS: The performed leukaphereses (one to five per patient) yielded a median of 16.6 x 10(6)/kg (range, 1.0 to 96.6 x 10(6)/kg) CD34(+) cells, which was sufficient for three reinfusions. Fifty patients (72%) completed the treatment according to schedule. Nine patients completed two courses, and six patients completed one course of treatment. The increase in dose-intensity was 290% that of a standard ICE regimen. The median duration of myelosuppression was similar between courses, namely 4 days (range, 1 to 12 days) for leukocytes less than 0.5 x 10(9)/L and 4 days (range, 0 to 22 days) for thrombocytes less than 20 x 10(9)/L. Febrile neutropenia developed in 66% of courses, severe diarrhea in 14%, mucositis in 10%, and nausea and vomiting in 21% of courses. There were six cases of toxic death (9%), most of which occurred in the first year of accrual and thus were attributable to the learning curve. The antitumor effect of the regimen was reflected in an 86% remission rate (95% confidence interval [CI], 74% to 93%), with 51% of patients achieving a complete response (95% CI, 38% to 63%). Median overall survival was 18 months for patients with limited disease and 11 months for patients with extensive disease. CONCLUSION: This multiple sequential high-dose ICE regimen could be safely administered on a multicenter basis to patients with small-cell lung cancer. The dose-intensity could be increased to 290% that of standard ICE regimen. The benefit of this approach is currently being tested in a randomized trial that aims to double the long-term rate of survival for patients with small-cell lung cancer.

Moderate dose-escalation of combination chemotherapy with concomitant thoracic radiotherapy in limited-disease small-cell lung cancer: prolonged intrathoracic tumor control and high central nervous system relapse rate. Groupe d'Oncologie-Pneumologie Clinique de l'Université Catholique de Louvain, Brussels and Liège, Belgium.

BACKGROUND: The role of chemotherapy dose-intensification in small-cell lung cancer (SCLC) remains unclear. This phase I-II study evaluates feasibility and outcome of combination chemotherapy at moderately elevated doses with concomitant thoracic radiotherapy in limited-disease SCLC. PATIENTS AND METHODS: Moderately elevated doses of ifosfamide-epirubicin (cycles 1 and 3) and of carboplatin-etoposide (cycles 2 and 4) were given with G-CSF and peripheral blood stem-cell (PBSC) support. Thoracic radiotherapy (40 Gy) was given once daily during the first five days of each cycle. RESULTS: Overall toxicity was acceptable; most common side-effects were myelosuppression and asthenia. All 35 eligible patients responded (23 CR, 12 PR). Median time to progression was 15 months: median overall survival was 24.6 months. Only 6 of 25 relapsing patients (24%) presented with a locoregional recurrence while 12 of 25 (48%) relapsed in the central nervous system (CNS). CONCLUSIONS: This regimen is a feasible dose-intensification with an acceptable toxicity profile. Its efficacy was demonstrated by a 100% response rate, an excellent local tumor control rate and a median survival of 24.6 months. In the absence of PCI, CNS relapse is a major problem if adequate local control is achieved.

Peripheral blood progenitor cell collections in cancer patients: analysis of factors affecting the yields.

BACKGROUND AND OBJECTIVE: Peripheral blood progenitor cells (PBPC) are now widely used to restore hematopoiesis following high dose chemotherapy in patients with malignancies. We sought to identify parameters that could predict the yield of PBPC after mobilization with chemotherapy (CT) with or without granulocyte colony-stimulating factor (G-CSF) in cancer patients. DESIGN AND METHODS: One hundred and fifty patients underwent 627 PBPC collections during the recovery phase following CT with (n = 469) or without (n = 142) G-CSF. Hemogram, CFC-assays and CD34+ cell count were performed on peripheral blood and leukaphereses products. After log transformation of the data, differences between groups were assessed with the unpaired t-test or one-way analysis of variance. RESULTS: Seventeen and two patients required 2 and 3 mobilization cycles respectively to reach our target of 15x10(4) CFU-GM/kg. In patients with lymphoma but not in those with leukemia, the yields of both CFU-GM and CD34+ cells/kg were dramatically increased when G-CSF was added to CT for mobilization. In collections primed with CT and G-CSF, better yields were obtained in patients with breast cancer or small-cell lung carcinoma (SCLC) as opposed to other solid tumors and leukemia. Among potential predictive factors of CT- and G-CSF-primed harvests, we found that the CD34+ cell count in peripheral blood (PB) was strongly correlated with both the CFU-GM and CD34+ cell yields. Except in leukemia patients, more than 1x10(6) CD34+ cells/kg were harvested when the CD34+ cell count in blood was above 20x10(6)/L. Similarly, better results were obtained in collections performed when the percentage of myeloid progenitors in blood on the day of apheresis was above 5 % or when the leukocyte count in blood was above 5x10(9)/L. INTERPRETATION AND CONCLUSIONS: A diagnosis of breast cancer or SCLC, a leukocyte count in PB of more than 5x10(9)/L, more than 5% myeloid progenitors or more than 20x10(6) CD34+ cells/L in PB were associated with higher yields of PBPC in collections mobilized with CT+G-CSF.