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Objectives: When advanced non-small-cell lung cancer (NSCLC) progresses during first-line treatment, re-biopsy may be indicated to detect a possible new biological profile (comparison to initial status, emergence of resistance biomarkers, or assessment of new biomarkers). The aim of this pragmatic prospective multicenter study was to assess the feasibility and clinical utility of re-biopsy in advanced NSCLC in a real-world setting., Methods: The main inclusion criteria were advanced NSCLC with an indication for repeat biopsy identified by the patient's clinician. The primary outcome was the percentage of successful procedures. Secondary outcomes were the type of procedure, new biological status, tolerability of the procedure, and clinical utility (treatment modification)., Results: From May 2012 to May 2013, 18 centers enrolled 100 patients (males: 44%; median age: 64.8 years; PS 0/1: 88%; adenocarcinoma: 89%; EGFR mutated: 50%; no initial biological profile: 16.4%). Re-biopsy was not possible in 19.5% of cases and provided no or too few tumor cells in 25.6% of cases. Repeat biopsy was useful for guiding treatment in 30.4% (25/82) of cases. Complications were infrequent (2 cases of moderate bleeding and 1 case of pneumothorax)., Conclusion: Re-biopsy of advanced NSCLC is feasible in the real-world setting, with acceptable adverse events. Guidelines are needed on the indications of re-biopsy, the choice of procedure, the sampling site, and laboratory analysis., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: In a Spanish Lung Cancer Group (SLCG) phase II trial, the combination of BRCA1 and receptor-associated protein 80 (RAP80) expression was significantly associated with outcome in Caucasian patients with nonsmall-cell lung cancer (NSCLC). The SLCG therefore undertook an industry-independent collaborative randomized phase III trial comparing nonselected cisplatin-based chemotherapy with therapy customized according to BRCA1/RAP80 expression. An analogous randomized phase II trial was carried out in China under the auspices of the SLCG to evaluate the effect of BRCA1/RAP80 expression in Asian patients., Patients and Methods: Eligibility criteria included stage IIIB-IV NSCLC and sufficient tumor specimen for molecular analysis. Randomization to the control or experimental arm was 1 : 1 in the SLCG trial and 1 : 3 in the Chinese trial. In both trials, patients in the control arm received docetaxel/cisplatin; in the experimental arm, patients with low RAP80 expression received gemcitabine/cisplatin, those with intermediate/high RAP80 expression and low/intermediate BRCA1 expression received docetaxel/cisplatin, and those with intermediate/high RAP80 expression and high BRCA1 expression received docetaxel alone. The primary end point was progression-free survival (PFS)., Results: Two hundred and seventy-nine patients in the SLCG trial and 124 in the Chinese trial were assessable for PFS. PFS in the control and experimental arms in the SLCG trial was 5.49 and 4.38 months, respectively [log rank P = 0.07; hazard ratio (HR) 1.28; P = 0.03]. In the Chinese trial, PFS was 4.74 and 3.78 months, respectively (log rank P = 0.82; HR 0.95; P = 0.82)., Conclusion: Accrual was prematurely closed on the SLCG trial due to the absence of clinical benefit in the experimental over the control arm. However, the BREC studies provide proof of concept that an international, nonindustry, biomarker-directed trial is feasible. Thanks to the groundwork laid by these studies, we expect that ongoing further research on alternative biomarkers to elucidate DNA repair mechanisms will help define novel therapeutic approaches., Trial Registration: NCT00617656/GECP-BREC and ChiCTR-TRC-12001860/BREC-CHINA., (© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Targeted therapies are now widely used for lung cancer management. Numerous biomarkers are performed in these patients in the diagnosis phase and have consequences on patient's management. There are some changes during elderly which can influence the biology of cancer; particularly mitochondrial dysfunction and deregulation of nutrient sensing. Elderly patients are candidate to these biological assessments, like younger ones., Methods: We review all the published papers based on Mesh carries with "elderly", "lung cancer", "targeted therapy"., Results: After description of biological modification during elderly, the use of targeted therapies in non-small cell lung cancer (NSCLC) is presented and discussed. Tyrosine kinase inhibitors (TKIs) and antiangiogenic molecules were depicted in selected or unselected population., Conclusions: Targeted therapies can be used in older patients with lung cancer and are sometimes an optimal choice in this particular population.

Background: The optimal treatment of large-cell neuroendocrine carcinoma (LCNEC) of the lung remains unclear. Here, our primary objective was to assess the efficacy of cisplatin-etoposide doublet chemotherapy in advanced LCNEC. Accuracy of the pathological diagnosis and treatment toxicity were assessed as secondary objectives., Patients and Methods: Prospective, multicentre, single-arm, phase II study with a centralised review of treatment-response and pathological data. Patients had untreated performance status (PS) 0/1 stage IV/IIIB LCNEC and received cisplatin (80 mg/m22 d1) and etoposide (100 mg/m22 d1-3) every 21 days., Results: Eighteen centres included 42 patients (mean age, 59 ± 9 years; 69% men; median of four cycles/patient). At least one grade-3/4 toxicity occurred in 59% of patients (neutropaenia, thrombocytopaenia, and anaemia in 32%, 17%, and 12%, respectively). The median progression-free survival (PFS) and overall survival (OS) were 5.2 months (95% confidence interval, CI, 3.1-6.6) and 7.7 months (95% CI, 6.0-9.6), respectively. The centralised pathologist review reclassified 11 of 40 (27.5%) patients: 9 as small-cell lung cancer, 1 as undifferentiated non-small-cell lung cancer, and 1 as atypical carcinoid. Survival data were not significantly changed by excluding the reclassified patients., Conclusions: The pathological diagnosis of LCNEC is difficult. The outcomes of advanced LCNEC treated with cisplatin-etoposide doublets are poor, similar to those of patients with advanced small-cell lung carcinoma (SCLC).

Summary: Elderly patients are often excluded from clinical trials, yet more than two-thirds of patients diagnosed with lung cancer are over 65 years old. It is therefore important to develop specific tools and trials for this specific patient population., Methods: This chapter first examines the management specificities of elderly patients. Randomized trials specifically involving elderly patients are then described, and likely future developments are considered., Results: Older people have several specificities. In addition to traditional criteria such as age and performance status, other important factors include the number of comorbidities and age-related changes such as cognitive deficits and depression. Specific indices taking these factors into account have been published and validated. Single-agent therapy has been widely used to treat metastatic lung cancer in the elderly, following publication of negative results from randomized phase III trials of combination chemotherapy. Recently, however, a trial of doublet therapy gave positive results, in a subgroup of independent older patients. The benefit of patient selection based on a combination of these indices has been demonstrated in open-label and randomized trials. These results must now be confirmed in phase III trials including the use of tyrosine kinase inhibitors combined with chemotherapy., Conclusions: Indices based on a combination of age-related factors, together with judicious use of biological markers, will further improve the prognosis of elderly lung cancer patients.

Primitive tumors of the trachea are rare, accounting for 0.1% of the airway tumors. Cystic adenoid carcinoma (or cylindroma) represents the second most frequent type of tracheal cancers. Histologically speaking, this tumor type is divided in three patterns: cribriform, tubular and solid; it presents a slow growth, perineural invasion and potential local recurrence and metastasis. We presented herein the case of a 56-year-old female suffering from a cystic adenoid carcinoma of the low trachea. She has been treated by carinal resection with negative airway margin and complete reconstruction, with the help of an extra corporeal membrane oxygenation (ECMO)., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Background: Brain metastases (BM) occur in up to 40% of non-small-cell lung cancer (NSCLC) patients. This trial assessed the safety and efficacy of pemetrexed-cisplatin in this population., Patients and Methods: Chemonaive NSCLC patients with BM ineligible for (radio)surgery, performance status (PS) of 0 to 2, were eligible for up to six cycles of cisplatin 75 mg/m(2) and pemetrexed 500 mg/m(2) every 3 weeks. Whole -brain radiotherapy was given in case of disease progression or at chemotherapy completion. Primary end point was objective response rate (RR) on BM. Secondary end points included extracerebral and overall RR, safety profile and survival., Results: Forty-three patients were enrolled. Initial characteristics were mean age 60.4 years; males 29; PS: 0 in 37.2%, 1 in 60.5% and 2 in 22.3% of patients; adenocarcinoma in 36 patients, large cell in 4 patients (nonsquamous, 93%) and squamous carcinoma in 3 patients. Functional classification of neurological status was stage I/II 86.0%, III 2.3% and IV 11.6%. Grade 3-4 hematological toxic effects were neutropenia, 11 patients (febrile neutropenia, 1 patient), and anemia, 6 patients. Non-hematological toxic effects were grade 2 urinary infection, one patient; grade 3 pneumonia, two patients; and grade 3 hypoacousia, one patient. Cerebral, extracerebral and overall RR by intent to treat analysis were 41.9%, 34.9% and 34.9%, respectively. Median survival time and time to progression were 7.4 and 4.0 months, respectively., Conclusion: Pemetrexed-cisplatin is an effective and well-tolerated regimen as first-line therapy for NSCLC patients with BM who always suffer a poor prognosis.

Background: Chemotherapy is the standard of care for advanced stages of non-small-cell lung cancer (NSCLC). TG4010 is a targeted immunotherapy based on a poxvirus (modified vaccinia virus Ankara) that codes for MUC1 tumour-associated antigen and interleukin 2. This study assessed TG4010 in combination with first-line chemotherapy in advanced NSCLC., Methods: 148 patients with advanced (stage IIIB [wet] or IV) NSCLC expressing MUC1 by immunohistochemistry, and with performance status 0 or 1, were enrolled in parallel groups in this open-label, phase 2B study. 74 patients were allocated to the combination therapy group, and received TG4010 (10(8) plaque forming units) plus cisplatin (75 mg/m(2) on day 1) and gemcitabine (1250 mg/m(2) on days 1 and 8) repeated every 3 weeks for up to six cycles. 74 patients allocated to the control group received the same chemotherapy alone. Patients were allocated using a dynamic minimisation procedure stratified by centre, performance status, and disease stage. The primary endpoint was 6-month progression-free survival (PFS), with a target rate of 40% or higher in the experimental group. Analyses were done on an intention-to-treat basis. This study is completed and is registered with ClinicalTrials.gov, number NCT00415818., Findings: 6-month PFS was 43·2% (32 of 74; 95% CI 33·4-53·5) in the TG4010 plus chemotherapy group, and 35·1% (26 of 74; 25·9-45·3) in the chemotherapy alone group. Fever, abdominal pain, and injection-site pain of any grade according to National Cancer Institute Common Toxicity Criteria were more common in the TG4010 group than in the chemotherapy alone group: 17 of 73 patients (23·3%) versus six of 72 (8·3%), 12 (16·4%) versus two (2·8%), and four (5·5%) versus zero (0%), respectively. The most common grade 3-4 adverse events were neutropenia (33 [45·2%] of patients in the TG4010 plus chemotherapy group vs 31 [43·1%] in the chemotherapy alone group) and fatigue (18 [24·7%] vs 13 [18·1%]); the only grade 3-4 events that differed significantly between groups were anorexia (three [4·1%] vs 10 [13·9%]) and pleural effusion (none vs four [5·6%]). 38 of 73 patients (52·1%) in the TG4010 plus chemotherapy group and 34 of 72 (47·2%) in the chemotherapy alone group had at least one serious adverse event., Interpretation: This phase 2B study suggests that TG4010 enhances the effect of chemotherapy in advanced NSCLC. A confirmatory phase 2B-3 trial has been initiated., Funding: Transgene SA, Advanced Diagnostics for New Therapeutic Approaches (ADNA)/OSEO., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Idiopathic tracheal stenosis (ITS) is a rare condition representing a difficult therapeutic challenge. Endoscopic management is a therapeutic option but long-term results are not established. The aim of this retrospective multicenter study was to analyze long-term outcome after endoscopic management of ITS., Methods: Nine institutions involved in interventional bronchoscopy were contacted and asked to identify ITS endoscopically treated. A standard form was used to report the main characteristics and long-term outcome after endoscopic management., Results: Twenty-three patients, 96% women, aged 45±16 years, were endoscopically treated for ITS. Time between first symptoms and diagnosis was 19±18 months. Bronchoscopy showed a weblike (61%) or complex (39%) stenosis, located in the upper part of the trachea, mainly in the cricoid area. Endoscopic treatment included mechanical dilation only (52%) or associated with laser or electrocoagulation (30%) and stent placement (18%). All procedures were efficient. The follow-up after endoscopic management was 41±34 months. The ITS recurrence occurred in 30% at 6 months, 59% at 2 years, and 87% at 5 years, with a delay of 14±16 months. The treatment of recurrence (n=13) included endoscopic management in 12 cases., Conclusions: Endoscopic management of ITS provides a safe and efficient therapeutic option but late recurrences are frequent and require long-term follow-up., (Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Introduction: TNF blockers are widely used to treat inflammatory rheumatic diseases and also in the treatment of extrapulmonary sarcoidosis. TNFα plays a major role in the development and persistence of sarcoid granulomata. However, recent studies have reported the involvement of anti-TNF therapies in the development of granulomatosis associated with the clinical and radiological features of sarcoidosis., Case Report: A 54-years-old man with ankylosing spondylitis was treated with etanercept for two years. He was admitted with symptoms of bronchitis associated with radiological evidence of bilateral pulmonary nodules and a right upper lobe infiltrate. Anti-TNF therapy was stopped even though the patient had received 3 months of prophylactic treatment with rifampicin and isoniazid before starting etanercept. Bronchoalveolar lavage excluded infection, particularly tuberculosis. The chest CT-scan showed bilateral pulmonary nodules with peribronchovascular micronodules and enlarged mediastinal lymph nodes. Surgical lung biopsy was performed and revealed non-caseating granulomata. All the data were consistent with a diagnosis of pulmonary sarcoidosis. The patient remained symptomatic despite discontinuation of etanercept for ten months. Corticosteroids were then introduced, leading to a clinical, functional and radiological improvement., Conclusion: This case report underlines the importance of studying the pulmonary complications of TNF blockers. The first priority is to exclude tuberculosis but a diagnosis of sarcoid-like granulomatosis has to be considered. Twenty-three cases have been described in the literature to date., (Copyright © 2011 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: The aim of this multicenter phase II trial was to evaluate the combination of oral vinorelbine and cisplatin with radiotherapy (RT) after cisplatin-docetaxel induction chemotherapy (CT) in patients with locally advanced non-small cell lung cancer (NSCLC)., Patients and Methods: Patients with previously untreated, inoperable, histologically or cytologically confirmed stage IIIA or IIIB NSCLC, with performance status ≤ 1 and weight loss ≤ 10% received two cycles of induction CT with cisplatin (75 mg/m) and docetaxel (75 mg/m) every 3 weeks. Patients with a tumor response or stabilization continued to receive cisplatin (80 mg/m) and oral vinorelbine (40 mg/m) on days 1 and 8 for two cycles, with concomitant thoracic RT (2 Gy/d, 5 d/wk, and total dose 66 Gy)., Results: Fifty-six patients were enrolled. All patients (n = 38) who received CT-RT were assessable for the tumor response. There were no complete responses. In the intent-to-treat analysis, the response rates were 32.1% after induction CT and 41.1% after CT-RT. The median progression-free and overall survival times were 9.2 months (95% confidence interval: 7-14) and 20.8 months (95% confidence interval: 13.7-24.1), respectively. Adverse effects of RT-CT were grades 3 to 4 neutropenia (four patients) and grade 3 esophageal toxicity (one patient). No treatment-related deaths occurred., Conclusion: The oral vinorelbine-cisplatin combination with concurrent RT is feasible and has a favorable risk-benefit ratio in stage IIIA/IIIB NSCLC.

Ras genes encode a family of membrane proteins involved in the regulation of cell growth. Mutations of Ras stimulate cell growth and thus can play a role in carcinogenesis. The search for mutations of Ras is possible by PCR on bronchial biopsies or surgical specimens. They are found in 15 to 20% of non-small cell lung cancers. In the disease's early stage, the presence of a Ras mutation can be a negative predictor of the effectiveness of adjuvant chemotherapy. In the advanced stage of the disease, it is a factor predicting a poor prognosis. Although prospective studies have found no statistically significant negative influence of the presence of a mutation of Ras on the effectiveness of tyrosine kinase inhibitors of EGFR, it is likely that these treatments will be of limited value in this population given the lack of response observed when Ras is mutated. Prospective and functional studies are needed to determine the value of the different mutations observed., (Copyright 2010 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Aspiration is a rare complication of video-capsule endoscopy. We report a case of asymptomatic aspiration of the capsule in a 90-year-old man. The diagnosis was obtained by the images taken by the capsule. Rigid bronchoscopy was used to remove the capsule. Recommendations to prevent this complication are: (1) Patients with swallowing disorders should have the capsule placed into the duodenum at the time of upper endoscopy. The capsule should never be placed in the stomach because of prolonged emptying times following endoscopy and IV sedation. (2) If a patient appears to have difficulty swallowing the capsule after two or three attempts, the capsule should be placed endoscopically. (3) When real-time capsule location is more readily available, the abdomen can be scanned after the initial ingestion to be sure that the capsule reached the stomach.

Background: TG4010 is a recombinant viral vector expressing both the tumor-associated antigen MUC1 and Interleukine-2. This vector is based on the modified virus of Ankara, a significantly attenuated strain of vaccinia virus. TG4010 has been designed to induce or amplify a cellular immune response directed against tumor cells expressing MUC1., Methods: A multicenter, randomized phase II study has explored two schedules of the combination of TG4010 with first line chemotherapy in patients with stage IIIB/IV non-small cell lung cancer. In Arm 1, TG4010 was combined upfront with cisplatin (100 mg/m day 1) and vinorelbine (25 mg/m day 1 and day 8). In Arm 2, patients were treated with TG4010 monotherapy until disease progression, followed by TG4010 plus the same chemotherapy as in Arm1. Response rate was evaluated according to RECIST. Median time to progression and median overall survival were calculated according to the Kaplan-Meier method., Results: Sixty-five patients were enrolled, 44 in Arm 1 and 21 in Arm 2, in accordance with the two stage Simon design of the statistical plan. In Arm 1, partial response was observed in 13 patients out of 37 evaluable patients (29.5% of the intent to treat population, 35.1% of the evaluable patients). In Arm 2, two patients experienced stable disease for more than 6 months with TG4010 alone (up to 211 days), in the subsequent combination with chemotherapy, one complete and one partial response were observed out of 14 evaluable patients. Arm 2 did not meet the criteria for moving forward to second stage. The median time to progression was 4.8 months for Arm 1. The median overall survival was 12.7 months for Arm 1 and 14.9 for Arm 2. One year survival rate was 53% for Arm 1 and 60% for Arm 2. TG4010 was well tolerated, mild to moderate injection site reactions, flu-like symptoms, and fatigue being the most frequent adverse reactions. A MUC1-specific cellular immune response was observed in lymphocyte samples from all responding patients evaluable for immunology., Conclusions: The combination of TG4010 with standard chemotherapy in advanced non-small cell lung cancer is feasible and shows encouraging results. A randomized study evaluating the addition of TG4010 to first line chemotherapy in this population is in progress.

The occurrence of pain during the course of bronchial carcinoma is nearly inescapable and often constitutes the main symptom for patients and those close to them. While pain control is held to be a priority of care in cancerology in the future, this goal is not always reached due to insufficient implementation of recommendations, however widely accessible. Our aim is to present the different aspects of pain treatment through the details of both pharmacological and nonpharmacological means.

Background: We conducted an economic analysis of a phase III clinical trial comparing sequential radiochemotherapy (RT-CT) with concurrent RT-CT in patients with locally advanced non-small-cell lung cancer., Patients and Methods: The trial was a randomized multicenter study comparing three cycles of chemotherapy (arm A) followed by radiotherapy against an RT-CT combination (two cycles of platinum etoposide) followed by two cycles of platinum-vinorelbine (arm B). The economic analysis adopted the payer's perspective and only included direct costs. Costs (euro, 1996-2003) were recorded until the cut-off date. A cost minimization analysis and a sensitivity analysis were carried out., Results: Data from 173 patients were used in the economic study. Protocol costs tended to be higher in arm B, while relapse costs were significantly higher in arm A. The total number of hospital days was higher in arm B. The average total cost per patient was euro16,074 in arm A and euro15,245 in arm B (P=0.15). The cost minimization analysis favored arm B. This advantage persisted in the sensitivity analysis., Conclusions: Concurrent RT-CT was not the more costly strategy in this phase III trial, despite lengthier hospitalization for toxicity. Other studies of similar design are needed to confirm these results in future randomized trials.

Extracellular matrix metalloproteinase inducer (EMMPRIN) was examined on bronchoalveolar lavage fluids (BALFs) and lung tissue from patients with fibrosis (usual interstitial pneumonia-idiopathic pulmonary fibrosis [UIP-IPF], n = 15; diffuse parenchymal lung diseases without IPF characteristics on computerized tomography scan, n = 8) and without fibrosis (n = 6). In UIP-IPF, EMMPRIN staining was increased in areas of fibrosis, mainly in macrophages and in epithelial cells. EMMPRIN was also found in the extracellular medium with significant levels in patients with lung fibrosis compared to subjects without fibrosis. Moreover, macrophages from patients with lung fibrosis spontaneously produce EMMPRIN. These findings show that EMMPRIN is increased in lung fibrosis.

Objective and Design: Chronic obstructive pulmonary disease (COPD) is characterized by an inflammatory process and airway remodeling involving matrix metalloproteinases (MMPs). Thus, we analyzed the expression and release of MMP-12 (macrophage metalloelastase) in bronchoalveolar lavage (BAL) and lung tissue from COPD patients and control subjects., Methods: Immunocytochemistry and immunochemistry were performed to analyze the expression of MMP-12 in BAL cells and bronchial biopsies. Western blotting was used for the evaluation of MMP-12 in BAL fluids., Results: The number of MMP-12 expressing macrophages together with the staining intensity was higher in BAL samples from COPD patients than in controls subjects. Similar results were noted in bronchial biopsies with higher MMP-12 expression in COPD subjects than in controls. Enhanced MMP-12 level was also observed in BAL fluids from patient with COPD in comparison to control subjects., Conclusion: This study demonstrated that COPD patients produce greater quantities of MMP-12 than controls, which may be a critical step in the pathogenesis of COPD and emphysema.

Study Objectives: Respiratory failure (RF) is a frequent cause of death among patients with bilateral bronchiectasis. An ICU admission is commonly required, and neither short-term or long-term outcomes have been studied., Design: We performed a retrospective study over a 10-year period (January 1990 to March 2000). All patients with bilateral bronchiectasis admitted for the first time in the medical ICU for RF were reviewed. Patients with cystic fibrosis were excluded., Measurements and Results: Forty-eight patients (mean age +/- SD, 63 +/- 11 years; mean simplified acute physiology score [SAPS] II, 32 +/- 12) of whom 25% received long-term oxygen therapy (LTOT) were identified. All the patients were treated with intensive medical care, associated with noninvasive ventilation in 13 patients (27%), and 26 patients (54%) required intubation. Nine patients (19%) died in the ICU. The 1-year mortality rate was 40%. Among the variables recorded at ICU admission, age > 65 years (p = 0.002), SAPS II score > 32 (p = 0.012), use of LTOT (p = 0.047), and intubation (p = 0.027) were associated with reduced survival in univariate analysis by Cox regression. Multivariate analysis by Cox proportional hazard model showed that age > 65 years (relative risk [RR], 2.70; 95% confidence interval [CI], 1.15 to 6.29) and use of LTOT (RR, 2.52; 95% CI, 1.15 to 5.54) were independently associated with reduced survival., Conclusions: We performed the first study providing information related to the impact of the first ICU stay for RF on long-term outcomes for patients with bilateral bronchiectasis. Age > 65 years and prior use of LTOT were associated with reduced survival.

Introduction: Erosion of mediastinal adenopathy into the bronchial tree is classically associated with tuberculosis. We describe two cases of of such bronchial erosion with Hodgkin's disease., Case Report: The first case was of a seventy-year old man with a history of pulmonary silicosis. A sub-carenal mass was identified during investigation of chronic cough. The bronchoscopy revealed an inflammatory stenosis due to Hodgkin's disease. The second case was of a thirteen-year old child whose Hodgkin's disease was thought to be in remission following treatment. The erosion of mediastinal adenopathy into the main left bronchus produced complete left pulmonary atalectasis, which required endobronchial stenting., Conclusions: In both cases, rigid bronchoscopy provided a histological diagnosis with diagnosis of Hodgkin's disease in the first case, and identification of recurrence in the other one. These cases are unusual. Such complications are usually complications of radiotherapy. Classically, erosion of mediastinal adenopathy into the bronchial tree is tuberculous in origin but they can be neoplasic.

Study Objectives: Intrapleural immunotherapy has shown some activity in patients with malignant mesothelioma. We conducted a multicentric pilot phase II study to evaluate the tolerance and the activity of intrapleurally infused autologous human activated macrophages (AM Phi) in patients with stage IA, IB, and IIA malignant pleural mesothelioma (MPM)., Design: AM Phi derived from in vitro monocyte culture were infused into the pleura of patients every week for 8 consecutive weeks. Each infusion was followed 3 days later by an intrapleural injection of 9 millions units of gamma-interferon (gamma-IFN) in an attempt to prolong the in vivo activation of infused AM Phi. Response was assessed by CT scan and thoracoscopy when possible. If the patient's disease progressed after AM Phi treatment, an additional treatment was left to the choice of the investigator., Patients: Nineteen patients with histologically proven stage IA, IB, or IIA MPM were enrolled. Two patients were excluded before any AM Phi infusion because of complications impeding infusion. Seventeen patients were actually treated. After completion of the AM Phi cellular therapy, 10 patients were treated with chemotherapy as their diseases progressed., Results: The overall response rate of patients actually treated was 14%. When including the two patients enrolled but not treated, the overall response "in intention to treat" was 11%; two patients had a partial response, with a duration of response of 30 months and 3 months, respectively. One patient, who could not be evaluated by thoracoscopy because of pleural symphysis, is still alive without any clinical or radiologic sign of disease 69 months after treatment. No major adverse effects were observed during the infusion of either AM Phi or gamma-IFN, and there was no interruption of treatment because of toxicity. However, symphysis was observed in 7 of 14 patients who received the complete treatment. The median survival of patients actually treated, including those who received chemotherapy after AM Phi, was 29.2 months., Conclusion: Combined infusion of AM Phi and gamma-IFN was well tolerated in patients with MPM; however, it had limited antitumor activity.

Background: No standard treatment is defined for elderly patients with small cell lung cancer (SCLC). Carboplatin and etoposide are highly active agents against SCLC. In this study, we evaluated the activity and toxicity of a combination of these two agents., Patients and Methods: Thirty-four untreated patients with limited or extensive SCLC and median age of 73.9 years entered the study. Chemotherapy consisted of carboplatin i.v. on day 1 (AUC 5 using Calvert's formula) and etoposide 100 mg/m(2) given orally on days 1-5, every 4 weeks, and thoracic irradiation was given to limited disease patients after chemotherapy., Results: The overall response rates was 59% (95% CI: 43-76). The median survival for all patients was 37 weeks (range 3-76 weeks). The toxicity was mainly haematological with grade 3-4 neutropenia in 59% of courses, febrile neutropenia in 15% of courses, and toxic death in 9% of patients., Conclusion: The results of this regimen are disappointing with worse response and survival, and more haematological toxicity than expected and previously reported, despite the use of Calvert's formula. Possible explanations are the use of etoposide per os rather than i.v., the frequent comorbidities of older patients and the inclusion of patients with poor prognosis factors.

The purpose is to determine the response to, and toxicity of docetaxel (Taxotère) in patients with inoperable non small cell lung cancer (NSCLC), previously untreated. Seventy patients with stage IIIB or IV NSCLC were treated by 100 mg/m2/ 3 weeks of docetaxel until tumor progression or severe toxicity. Premedication with diosmine and prednisolone was given in all patients: 66/70 were eligible and 55/70 were assessable for antitumoral activity. Median age: 63 years, WHO performans status 0-1: 83%, stage IV: 96%. For eligible patients, 17/66 (26%) achieved an objective response: 1 complete response and 16 partial response (IC 95% = 15-36). With a median follow-up of 23.4 months (range 14.9-28.7), for evaluable patients, the median response duration was 8 months, the median time to progression 4 months, and the median survival time 10 months. The median number of administered cycles is 5 (range 1-12). The estimate one year survival rate was 47%. Seventy-six patients presented neutropenia (grade 3-4); febrile neutropenia was observed in 7% of cycles. Non haematological toxicities are: fluid retention related to docetaxel (2.9%), diarrhea (6%), nausea-vomiting (4%), asthenia (3%), nail changes (6%). Docetaxel (Taxotère) administered at 100 mg/m2/3 weeks has relevant clinical activity in previously untreated NSCLC with a acceptable toxicity.

Purpose: Determine the response to, and toxicity of docetaxel (Taxotere) in patients (pts) with inoperable non-small-cell lung cancer (NSCLC) previously treated with platinum-containing chemotherapy., Patients and Methods: Twenty-seven patients with stage IIIB or IV NSCLC, having received one platinum-containing regimen were treated with 100 mg/m2/3 weeks of docetaxel until tumor progression or severe toxicity. Premedication with prednisolone and diosmin was given in all patients. Antitumoral activity was assessable in 21/27 pts. Median age: 52 years; WHO performance status 0-1: 77% pts, stage IV disease: 63% pts., Results: 6/21 eligible pts (24%) achieved a partial response to treatment [C.I 95%: 5.6-42]. Median time to progression: 2.9 months, median survival: 8.5 months with a median follow-up of 23.7 months (range: 13.5-27). Hematologic toxicity: grade 3-4 neutropenia: 75% pts, febrile neutropenia: 11% cycles. Non hematologic toxicities: fluid retention, rash, alopecia, sensory neuropathy, asthenia, and nail changes., Conclusion: Docetaxel (Taxotere) administered at 100 mg/m2/3 weeks has relevant clinical activity against platinum treated NSCLC pts. Neutropenia is the main toxicity.

Purpose: To assess the toxicity and efficacy of high dose ifosfamide in stage IV NSCLC., Methods: In a previous trial, we have determined maximum tolerated dose for 3-days ifosfamide treatment by 3-weeks schedule as 9 g/m2 according to hematologic tolerance. We therefore set up a phase II to study the toxicity and efficacy of this schedule in chemotherapy naive metastatic NSCLC. Ifosfamide (+ mesna 1 g/m2) was administered by a two hour infusion (3 g/m2) for three days every three weeks. Patients received three mesna bolus infusions (1 g/m2) at 4, 8 and 12 hours after the end of ifosfamide infusion. Antitumoral efficacy was performed after 2 cycles and treatment could be pursued for responding patients until disease progression. From september 1995 to January 1997, 31 patients have been included in this study. Median age was 60.7 years +/- 1.33 (41-70) for 27 males and 4 females. Patients (pts) presented metastases in lung for 10 pts, bone for 10 pts, liver for 6 pts, adrenal for 4 pts and multiorgan metastatic localisation for 1 patient. Seven patients were unassessable: 1 lost for follow-up, 1 sudden death, 5 treatment interruptions before evaluation time and 3 toxic deaths (9.6%)., Toxicity: neutropenia grade 4 (10 pts and 1 death), cardiotoxicity grade 4 (1 pt) and 2 deaths following neurotoxicity grade 4. We achieve 4 partial responses (13%, 95CI: 3.6-29.8), 10 progressive diseases (32.3%, 95CI: 16.7-51.4) and 10 stabilizations (32.3%, 95CI: 16.7-51.4). Median response duration was 91 days +/- 55 d. Median survival was 9.3 months, e.g. 280 days (8-863). Overall survival at one year is 48%., Conclusion: This modality of high dose ifosfamide is as effective as standard monotherapy schedules in stage IV NSCLC. Unexpected toxicities particularly hematological ones could be due to a short duration of fractionated treatment. Results in term of survival leads us to further evaluate ifosfamide monotherapy treatment on a 5-day schedule basis.

Mature teratoma is the most frequent primary germ-cell tumor occurring in the mediastinum. These tumors present characteristic mature cells derived from all three types of embryogenesis tissues. We report two cases. The typical presentation is a cyst-like noninvasive, heterogeneous and calcified formation in the anterior mediastinum, usually in young subjects. Tumor markers, alpha-fetoprotein and beta-gonadotropin, are contributive as they rule out mature tumors if positive. Surgery is the treatment of choice, although adherence to neighboring structures usually makes complete excision difficult. Pathology provides the precise diagnosis, ruling out an immature component.

Background and Study Aims: Locoregional progression of esophageal cancer can result in respiratory distress aving to tracheoesophageal (T-E) fistula or central airways stenosis. We report our experience of airway stenting in 51 patients with esophageal carcinoma involving the central airways., Patients and Methods: All data were recorded retrospectively. Fifty-one patients (44 men and seven women), with a mean age of 58.6 years, were analyzed. All had an esophageal squamous cell carcinoma. Severe respiratory impairment due to tumor invasion or to a tracheobronchial fistula (n= 14) was present in all patients. Nine of the 14 patients with fistula had dysphagia. Among the 37 patients without fistula, 19 had dysphagia., Results: Sixty-six tracheobronchial stents were inserted in 51 patients: 65 Dumon stents and one Wallstent. Forty stents were implanted in the trachea, 16 in the left main bronchus and 10 in the right main bronchus. In 47 patients there was a significant improvement of respiratory symptoms. Esophageal intubation, carried out in nine patients, allowed eating and drinking in all cases. Mean survival was 107.7 days, with the longest follow-up 587 days. There was no difference between mean survival in the patients with fistulae (103.3+/-days) and the others (109.3+/-days). In two cases stent placement was responsible for death (massive hemoptysis and pneumonia). The main complications were migration (n=6), granuloma (n=2), pneumonia (n=2) and pneumothorax (n = 2). In 13 patients tumor progression in the airways was noted from one to 11 months after stenting, inducing a relapse of dyspnea., Conclusions: Complications are easily detected by the appearance of respiratory symptoms and do not necessitate systematic flexible bronchoscopy, but only preventive measures such as regular aerosol therapy, adapted respiratory physiotherapy and regular clinical follow-up.

Lung damage due to inhalation of inflammable products, especially Kerdane, is mainly observed in young subjects. Lung damage is rarely severe and the diagnosis is facilitated by the notion of inhalation. These conditions regress favorably in a few days. We report six cases.

Epithelioid haemangioendothelioma of the pulmonary vessels is a rare neoplasm which usually has a minimal clinical expression. The present case report describes an exceptional case with severe inaugural alveolar haemorrhage which led to death by acute respiratory failure within a few weeks.

The main respiratory manifestations of amylosis are tracheobronchial involvement and modular or diffuse parenchymal disease. Amyloid deposits in the pleura are exceptional. We observed transsudative pleural effusion and heart failure in a patient with multiple myeloma, leading to the discovery of pleural amylosis. Amyloid deposits in the pleura may be fortuitous discoveries since pleural effusion is not necessarily observed. It is however important to be aware of this possibility since the localization is easily accessible for diagnosis. Specific stains are effective diagnostic tools even for transsudative effusions, particularly in suggestive clinical conditions such as multiple myeloma.

Serious acute asthma is a reality. The authors detail the factors that cover the areas usually met, the signs that are portents of a worrying development, regrouped to the threshold of the entirety of the "menacing syndrome", finally the signs of severity or distress, as well as the recommended treatments.

The authors report two cases of myelomatosis localised to the pleura, one of which was associated with an adenocarcinoma. Pleural effusions are relatively rare during the course of multiple myeloma and most often occur with non-specific disorders of the disease. The myelomatous origin of a pleural effusion can only be made by analysis of the pleural fluid and should be recognised early enough to enable aggressive treatment to be instituted even if the prognosis associated with such a localisation is very poor.

We report a fatal case of acute interstitial pneumonitis in a patient treated with carmustine (BCNU) for a brain tumor. Bronchoalveolar lavage (BAL) revealed lymphocyte alveolitis with a low CD4/CD8 ratio (0.36), consistent with an immunoallergic phenomenon, rather than the most often evoked toxic hypothesis.

Sarcoidosis is diffuse granulomatosis disease. The aetiology and pathogenesis are unknown. Many different localizations have been described together with immunological disturbances. Generally, the prognosis is favourable. Here we describe the pulmonary manifestations and their staging. Extra-pulmonary manifestations are then presented. Finally, the principle elements of the diagnosis and the treatment of sarcoidosis are discussed.