[Systemic nocardiosis with mediastinal lymph node involvement proven by endoscopic ultrasound]. / Nocardiose systémique avec atteinte ganglionnaire médiastinale prouvée par échoendoscopie.

INTRODUCTION: Systemic nocardiosis is an infectious disease that is rarely associated with mediastinal lymph nodes. CASE REPORT: We report the case of a 72-year-old male patient treated with a high dose of oral corticosteroids for rheumatoid polyarthritis. This patient presented with rapid overall deterioration associated with mediastinal lymph nodes. Endobronchial ultrasound enabled us to establish a diagnosis of systemic nocardiosis. The patient recovered after having received suitable antibiotic treatment for four months. CONCLUSION: This work reports on a rare clinical presentation of systemic nocardiosis associated with mediastinal lymphadenopathies and highlights the key role of endobronchial ultrasound in diagnosing mediastinal lymph nodes, especially in differential diagnosis for lung cancer.

Evaluation of the combination of oxaliplatin and 5-fluorouracil or gemcitabine in patients with sporadic metastatic pulmonary carcinoid tumors.

OBJECTIVES: The aim of this retrospective study was to analyse the efficacy of gemcitabine-oxaliplatin (gemox) or 5-fluorouracil-oxaliplatin (folfox) in the treatment of metastatic pulmonary carcinoid tumors. PATIENTS AND METHODS: 45 patients were included in two tertiary referral centers between January 1999 and January 2013. Typical, atypical carcinoids or not otherwise specified carcinoids were diagnosed according to WHO criteria in 19%, 57%, and 24% of cases by two expert pathologists. Patients had synchronous (38%) or metachronous (62%) metastastic disease (median of 2 (1-5) metastatic sites). Seventy-nine percent had progressive disease before start of chemotherapy. Treatment consisted of: gemcitabine 1000mg/m(2) and oxaliplatin 100mg/m(2) every 2 weeks (gemox regimen, n=24) or 5-fluorouracil (5-FU) (400mg/m(2) in bolus injection and 5-FU 2400mg/m(2) in 46h-infusion) and oxaliplatin 85mg/m(2) (folfox regimen, n=21) every 2 weeks. Tumor response was assessed according to RECIST criteria every 8-12 weeks. Progression free survival and overall survival were assessed using Kaplan Meier curves. RESULTS: Patients received oxaliplatin-based chemotherapy in first-line (20%), second-line (33%), or post-second-line (47%) systemic treatment. The median number of cycles was 8 (1-12). Nine (20%) stopped oxaliplatin before 8 cycles because of toxicity. Nine patients (20%) had a partial response and 29 (64%) had stable disease. Median progression free survival (PFS) was 15 (6-25) months. Median overall survival (OS) was 34 (21-49) months. No significant difference was observed in response and PFS between either regimens. CONCLUSIONS: Our results suggest that either gemcitabine-oxaliplatin or 5-fluorouracil-oxaliplatin combinations are attractive chemotherapy regimen in metastatic pulmonary carcinoid tumors.

Impact of Continuing First-Line EGFR Tyrosine Kinase Inhibitor Therapy Beyond RECIST Disease Progression in Patients with Advanced EGFR-Mutated Non-Small-Cell Lung Cancer (NSCLC): Retrospective GFPC 04-13 Study.

UNLABELLED: Retrospective studies suggested a benefit of first-line tyrosine kinase inhibitor (TKI) treatment continuation after response evaluation in solid tumors (RECIST) progression in epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) patients. The aim of this multicenter observational retrospective study was to assess the frequency of this practice and its impact on overall survival (OS). The analysis included advanced EGFR-mutated NSCLC patients treated with first-line TKI who experienced RECIST progression between June 2010 and July 2012. Among the 123 patients included (67 ± 12.7 years, women: 69 %, non smokers: 68 %, PS 0-1: 87 %), 40.6 % continued TKI therapy after RECIST progression. There was no difference between the patients who did and did not continue TKI therapy with respect to progression-free survival (PFS1: 10.5 versus 9.5 months, p = 0.4). Overall survival (OS) showed a non-significant trend in favor of continuing TKI therapy (33.0 vs. 21.2 months, p = 0.054). Progressions were significantly less symptomatic in the TKI continuation group than in the discontinuation group (18 % vs. 37 %, p < 0.01). Univariate analysis showed a higher risk of death among patients with PS >1 (HR 4.33, 95 %CI: 2.21-8.47, p = 0.001), >1 one metastatic site (HR 1.96, 95 %CI: 1.06-3.61, p = 0.02), brain metastasis (HR 1.75, 95 %CI: 1.08-2.84, p = 0.02) at diagnosis, and a trend towards a higher risk of death in cases of TKI discontinuation after progression (HR 1.62, 95 %CI: 0.98-2.67, p = 0.056 ). In multivariate analysis only PS >1 (HR 6.27, 95 %CI: 2.97-13.25, p = 0.00001) and >1 metastatic site (HR 2.54, 95 %CI: 1.24-5.21, p = 0.02) at diagnosis remained significant. This study suggests that under certain circumstances, first-line TKI treatment continuation after RECIST progression is an acceptable option in EGFR-mutated NSCLC patients. CLINICAL TRIAL INFORMATION: NCT02293733.

[Tumor-bronchial actinomycosis simulating a recurrence of lung cancer 14 years after initial treatment: A case report]. / Actinomycose bronchique pseudo-tumorale simulant une ré-évolution d'un cancer bronchique 14ans après la prise en charge thérapeutique initiale : à propos d'un cas.

A patient with a history of squamous cell carcinoma of the right upper lung lobe treated 14 years before by concomitant chemo-radiotherapy was referred on account of dyspnea. Bronchial endoscopy revealed complete obstruction of the right main bronchus highly suggestive of a tumor recurrence. However, biopsy samples only showed inflammatory and necrotic tissue with no evidence of malignancy. Despite complete tissue resection by rigid bronchoscopy, a rapid and complete recurrence occurred requiring the placement of a Y-shaped bronchial prosthesis. Repeat histological, bacteriological and mycological analyses were negative. The patient was soon readmitted to hospital for a lung infection due to recurrence of obstruction inside and around the prosthesis. Bacterial examination of biopsy samples identified Actinomyces meyeri. Appropriate antibiotic therapy led to a complete regression of the bronchial obstruction. Unfortunately, the patient died a few months later due to massive hemoptysis after the removal of the prosthesis. Autopsy examination showed a fistula between the right main bronchus and pulmonary artery, with no evidence of neoplastic recurrence nor the persistence of lesions associated with actinomycosis.

[Late revelation of air embolism after transthoracic needle biopsy]. / Embolie gazeuse de révélation tardive après ponction transpariétale pulmonaire.

INTRODUCTION: Percutaneous transthoracic needle biopsy is a useful and common procedure in the investigation of a lung nodule. The occurrence of air embolism after percutaneous transthoracic needle biopsy is extremely rare. CASE REPORT: We report a 62-year-old woman who presented with neurological signs including restlessness, meningeal signs and focal neurologic deficits 4 hours after percutaneous transthoracic lung biopsy, related to air embolism. The outcome was favorable with hyperbaric oxygen therapy. CONCLUSION: Percutaneous transthoracic needle biopsy complicated by air embolism has been rarely reported. It usually occurs within minutes after the biopsy. The late onset of this adverse event in our patient is exceptional. Air embolism occurs more frequently after biopsy of lung infiltrates compared to nodules. Occurrence of a pneumothorax or an intraalveolar haemorrhage following a percutaneous transthoracic needle biopsy may be warning manifestations and justify a close monitoring.

[Predictive factors for acute radiation pneumonitis]. / Facteurs prédictifs de la pneumopathie radique aiguë

Thoracic irradiation is a major weapon in the treatment of nonmetastatic primary lung cancer, in particular in patients presenting a locally advanced disease of the mediastinium. Acute radiation pneumonitis (ARP) is one of the main limiting toxicities. The purpose of this work is to sum up the current state of knowledge of the factors of risk of developing ARP. The incidence after conventional irradiation, in patients with non small cell lung cancer (NSCLC) is about 7 to 10% in the moderate although symptomatic forms of ARP and about 1 to 3% in the severe forms. The factors related to the patient, the tumour or treatments prior to the irradiation do not determine any specific risk of ARP besides an age of over 65 years that remains debatable. The validated predictive factors of ARP are mainly related to the irradiation factors (healthy lung volumes irradiated, average dose of irradiation, etc.). Nevertheless, in spite of the adjustment of these parameters, the individual susceptibility to the toxicity of thoracic radiotherapy remains significant, directing current research to the biological markers intrinsic to the patient. In particular, the involvement of early variations of certain cytokines (IL-6, IL-10, TGF-ss) in the occurrence of ARP during irradiation has been suggested and studies are under way to confirm their involvement and determine their role.

[Bevacizumab and non-small cell lung cancer: a new step?]. / Bevacizumab et cancer bronchique non à petites cellules: une nouvelle étape?

Inhibition of specific processes essential for tumour vascular development is one of the key strategies for the treatment of non- small cell lung cancer (NSCLC). Many agents target the Vascular Endothelial Growth Factor (VEGF) pathway, either by preventing VEGF receptor binding or inhibiting VEGF receptor signalling in endothelial cells. Bevacizumab is a monoclonal antibody specific for VEGF-A. Combination of bevacizumab with standard first-line chemotherapy in NSCLC leads to an improvement in response rates and progression-free survival compared to chemotherapy alone and a significant survival advantage with carboplatin- paclitaxel chemotherapy. Toxicity issues are of concern with the possible occurrence of hypertension and an increased risk of arterial thrombo-embolism. The occurrence of fatal pulmonary haemorrhage after necrosis of the primary tumour is a specific toxicity in NSCLC which requires appropriate selection of patients before treatment; excluding squamous cell carcinoma, haemorrhagic tumours and tumour invasion of major blood vessels. The use of bevacizumab combined with chemotherapy represent a first step in the development of antiangiogenic treatments in NSCLC, with the future possibility of using it in earlier stages of disease.

[Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia: a rare preneoplastic condition]. / L'hyperplasie neuroendocrine pulmonaire idiopathique: une lésion prénéoplasique méconnue.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is an uncommon preneoplastic condition, often associated with typical carcinoid tumours. The observations reported below concern two women, both suffering from chronic pulmonary symptoms. These patients underwent computed tomography that showed a solitary nodule in the first patient and multiple sub centimetre nodules in the second. In both cases histological studies of the pulmonary biopsies revealed: a proliferation of neuroendocrine cells dispersed in the bronchial and bronchiolar epithelium, more specifically superficial to the basement membrane; some tumourlets; a typical carcinoid tumour was also found in the first patient's biopsy. The choice of treatment remains difficult, mainly because the existing studies are restricted to small numbers of patients or isolated cases, a consequence of the low prevalence of this disease. Considering its slow evolution, management by long-term clinical, endoscopic and radiologic surveillance may be considered. If a carcinoid tumour is present or appears during the surveillance, the standard treatment is still surgical resection.

[Idiopathic constrictive péricarditis revealed by a massive left pleural effusion]. / Epanchement pleural gauche massif révélateur d'une péricardite constrictive idiopathique.

INTRODUCTION: We report a case of constrictive péricarditis initially revealed by a massive left sided pleural effusion. CASE REPORT: The patient was dyspnoeic without any associated clinical signs. Only cardiac catheterization gave the diagnosis with a characteristic dip-plateau of the right ventricle. After full assessment, no aetiology was found. CONCLUSION: After a treatment with corticosteroids, the progress has been favourable to date.

[Tyrosine kinase inhibitors in the management of non-small cell lung cancer]. / Les inhibiteurs de tyrosine kinase de l'EGFR dans le traitement du CBNPC.

The epidermal growth factor receptor (EGFR) plays an important role in non-small cell lung cancer growth. Small molecules can specifically target the tyrosine kinase activity of the EGFR's intracellular domain and thus inhibit downstream pathways influencing cell proliferation and survival. Gefitinib and erlotinib have been developed as single-agents for the treatment of patients who have relapsed following one or more courses of chemotherapy. Erlotinib has exhibited significant overall survival benefit in a second- or third-line setting compared to placebo for unselected patients. A beneficial effect on survival has been observed in almost all subgroups of patients and the response rate was higher in women, non-smokers, Asian patients and patients with adenocarcinoma. Somatic mutations in the tyrosine kinase domain of EGFR have been shown to be strong predictive markers for drug response to gefitinib or erlotinib and led to a new insight into adenocarcinoma carcinogenesis. High EGFR gene copy number seems to be predictive of EGFR tyrosine kinase inhibitors-related effect on survival observed in second- or third-line treatment. Future use of EFGR tyrosine kinase inhibitors should be based on improved clinical and molecular selection of patients who are likely to derive the greatest benefit from these drugs, especially in first-line setting.

Prospective evaluation of early lung toxicity following three-dimensional conformal radiation therapy in non-small-cell lung cancer: preliminary results.

PURPOSE: Radiation pneumonitis is the restricting complication following lung cancer irradiation. The correlation between dose-volume histograms (DVHs) and pneumonitis, with a clinical, radiological, and respiratory function evaluation was assessed. Special endpoint was the evaluation of respiratory function after three-dimensional conformal radiotherapy (3D-CRT). METHODS AND MATERIALS: Fifty-four patients with non metastatic non-small-cell lung cancer (NSCLC) were treated with a curative intent with 3D-CRT (66 Gy). Thirty-one patients were treated postoperatively (pneumonectomy in 9 patients) for residual tumor or massive nodal involvement (N2 or N3); 23 patients were treated with exclusive radiotherapy. Clinical evaluation, CT scan, and pulmonary functional tests were performed before and 6 weeks after irradiation. The DVHs were calculated applying lung density heterogeneity. RESULTS: Twenty patients had radiation pneumonitis. Irradiation significantly decreased total lung capacity. Volume of the PTV2 (more than 200 cm(3)) was a significant prognostic factor for lung complication. CONCLUSION: DVHs combined with initial pulmonary functional tests can predict pulmonary toxicity and could allow us to adjust volume that received total highest dose with acceptable toxicity.

Small-cell lung cancer: patients included in clinical trials are not representative of the patient population as a whole.

PURPOSE: To determine the clinical characteristics of the subpopulation of patients not included in clinical trials, their outcome, and the reasons for their ineligibility and non-participation. PATIENTS AND METHODS: We studied 57 patients (out of 178 consecutive patients with SCLC), who were not included in any of the three successive clinical trials completed at our center during the study period. We also compared 37 patients excluded from the largest clinical trial to their 73 included counterparts. RESULTS: Reasons for ineligibility (n = 53) included low Karnofsky index (n = 17), advanced age (n = 12), non-feasible long-term follow-up (n = 12), previous history of cancer (n = 8), contraindication for anthracyclines (n = 5), and other medical reasons (n = 11). Only four eligible patients were not included in the trials. As compared to patients included in the studies, non-included patients had a significantly lower Karnofsky index, were older, presented more frequently with metastatic disease, and had a lower response rate to treatment and a shorter survival. However, exclusion from the trial was not an independent prognostic factor by multivariate analysis. CONCLUSIONS: Selection biases were unlikely in the three trials, based on the high ratio of included/eligible patients. However, the subgroup of patients included in the trials was not representative of the patient population as a whole because of restrictive eligibility criteria. Results from published clinical trials to the overall population should be extrapolated only with caution. We suggest that the proportion and major characteristics of ineligible and non-participating patients be mentioned in any publication of a clinical trial.

[Tracheal stenosis of inflammatory aspect]. / Sténose trachéale d'aspect inflammatoire.

We report a case of tracheal leishmaniasis with stenosis in a 52 year-old female originative from the Gard region (South of France). The unusual localization acknowledges for the difficulties met in setting the diagnosis which was established through cytological examination of bronchial brushing. Though rare, leishmaniasis infection must be suspected in all cases of mucosal lesions occurring in patients living in endemic areas.

The limits of chemotherapy dose intensification using granulocyte colony stimulating factor alone in extensive small cell lung cancer.

Human Recombinant Granulocyte Colony Stimulating Factor (G-CSF) allows rapid neutrophil recovery after chemotherapy-induced leukopenia. In a prospective series of 54 patients with extensive small cell lung cancer, we evaluated the feasibility and efficacy of accelerated delivery of the AVI chemotherapy regimen. Treatment consisted of Doxorubicin 50 mg/m2 day 1, Etoposide 120 mg/m2 day 1-3 and Ifosfamide 2 g/m2 (+ Mesna 4 g) day 1 and 2 given every 2 weeks and followed by G-CSF (Neupogen, Amgen Roche 5 micrograms/kg/day s.c. day 4-14). Twenty-seven (50%) patients could not receive the total of six courses, seven because of severe septic complication, 10 because of Grade 4 thrombopenia, seven because of non-response and three because of patient refusal. Chemotherapy had to be delayed in 58 out of the 244 administered courses and this was due to thrombopenia in 48% of cases. The probability of optimal dose-on-time administration was 64% at three courses. The mean actually received dose intensity was 93% at six courses (27 patients treated). It was increased by 76% compared to our previously published conventional 3-week interval chemotherapy. The median neutrophil nadirs were stable during the successive treatment courses while haemoglobin and platelet values significantly worsened from cycle 1 to cycle 6. The overall response rate after three courses was 77% in the 48 evaluable patients. The median survival is 8 months overall and 5 months disease free. The actuarial survival is 22% at 2 years. We conclude that substantial dose intensification with accelerated chemotherapy and G-CSF support is feasible. However, the rate of severe infectious episodes is too high and thrombopenia is the main limiting factor. Either growth factors active on the megacaryocytic lineage or haematological rescue with peripheral blood stem cells might be useful in this setting.

Clinical and radiological aspects of Villaret's syndrome.

A 68-year-old man with a history of large cell lung carcinoma presented 1 year after surgical management of the initial lesion, with a complete unilateral IX-XII cranial nerve palsy with Horner's sign. This rare multiple cranial nerve palsy is called Villaret's syndrome. It suggests an extracranial lesion located in the retroparotid space. Complete basal skull radiology work up including computed tomography and magnetic resonance imaging confirmed the location of the causal lesion in the retroparotid space.

Catheter-related bacteremia associated with coagulase-positive Staphylococcus intermedius.

We report a case of catheter-related bacteremia in a 63-year-old patient caused by Staphylococcus intermedius. Clinical resolution of the infection was obtained after removal of the intravenous device and antibiotic treatment. This observation emphasizes the risk of confusion between S. intermedius and Staphylococcus aureus if only a coagulase test is done.

Bone marrow metastases detection in small cell lung cancer. A review.

Small cell lung cancer is known to carry a high capacity to metastasize in various sites including bone marrow. We here review the respective sensitivities of classical cyto-histological methods and of more recently described techniques such as cell cultures, immunostaining with monoclonal antibodies and magnetic resonance imaging. These new and somehow less aggressive methods allow the detection of malignant cells in 50% or more of patients with small cell lung cancer. However, their potential usefulness in the staging of such patients as well as their therapeutic and clinical implications remain undetermined. Their possible clinical value needs to be evaluated in future trials.