Joaquim Majó

Gene Expression as a Predictive Marker of Outcome in Stage IIB-IIIA-IIIB Non-Small Cell Lung Cancer After Induction Gemcitabine-Based Chemotherapy Followed By Resectional Surgery

Purpose: The first suggestions of a relationship between gene mRNA expression and differential sensitivity to gemcitabine/cisplatin are now emerging. ERCC1, RRM1, and XPD are involved in the nucleotide excision repair pathways, and tumor up-regulation of these genes leads to chemotherapy failure. In the present study, we have examined the potential correlation and predictive value of ERCC1, RRM1, and XPD mRNA expression in resected specimens from 67 stage IIB, IIIA, and IIIB non-small cell lung cancer patients treated with neoadjuvant gemcitabine/platinum followed by surgery Experimental Design: ERCC1, RRM1, and XPD expression was quantified using real-time quantitative reverse transcription-PCR. Results: A good correlation was found between mRNA expression levels of the three genes. For RRM1 levels, patients in the bottom quartile had a decreased risk of death compared with those in the top quartile (risk ratio = 0.30; P = 0.033). Median survival for the 17 patients in the bottom quartile was 52 months, whereas for the 15 in the top quartile, it was 26 months (P = 0.018). When the characteristics of these 17 patients were compared with all of the other 50 patients, no differences in initial staging were observed. However, the 17 patients in the bottom quartile had better outcomes, including more radiographic responses (65% versus 54%; P = 0.24), complete resections (94% versus 72%; P = 0.03), lobectomies (71% versus 34%; P = 0.004), and pathological complete responses (29% versus 0%; P = 0.00001) Conclusions: Patients with RRM1 levels in the bottom quartile benefited significantly from gemcitabine/cisplatin neoadjuvant chemotherapy, leading us to conclude that RRM1 mRNA levels should be additionally validated to proceed with tailored chemotherapy.

Diagnoses and Diagnostic Procedures in 500 Consecutive Patients With Clinical Suspicion of Interstitial Lung Disease

OBJECTIVE To determine the diagnostic yield achieved with the application of current recommendations for evaluating patients with suspected interstitial lung disease (ILD) and the procedures that must be applied to reach a definitive diagnosis. PATIENTS AND METHODS Over a 10-year period, 500 consecutive patients attending an ILD outpatient clinic who showed features of diffuse lung involvement were assessed with a single diagnostic protocol. Results were introduced in a dedicated database and diagnoses for idiopathic interstitial pneumonia were established according to a recent consensus classification. RESULTS A definitive diagnosis was reached in 427 (85%) patients: in 125 without invasive procedures and in 302 with invasive procedures. In 73 (14.6%) cases a definitive diagnosis was not reached, and patients were placed in the group of unclassifiable interstitial pneumonia. Idiopathic interstitial pneumonia was the predominant group with 193 (39%) patients. The main specific entities included sarcoidosis with 93 (19%) patients, usual interstitial pneumonia with 84 (17%) patients, and hypersensitivity pneumonitis with 75 (15%) patients. Thirty (6%) patients were diagnosed with an illness other than ILD (false ILD). In 332 patients, we performed a total of 433 invasive procedures: transbronchial biopsy in 252 (direct diagnostic yield, 38%, or if used also to exclude other specific diagnosis, 50%), bronchoalveolar lavage in 260 (yield, 5%), and open lung biopsy in 141 (yield, 93%). Hence, following the current diagnostic approach, a definitive diagnosis was established for 85% of patients, for 25% solely on clinical grounds and imaging criteria and for 60% on the basis of invasive procedures. Diagnosis by open lung biopsy was still required for 141 (28%) patients. CONCLUSIONS The diagnostic yield was high when the recommended study protocol was followed. A quarter of the diagnoses were reached with clinical criteria alone, but another quarter could only be made after open lung biopsy.

Neumonía intersticial no específica: Características clínicas y epidemiológicas

BACKGROUND AND OBJECTIVES: Patients diagnosed with non-specific interstitial pneumonia (NSIP) in 2 hospitals in Barcelona, Spain, were studied to investigate the factors that could contribute to the etiology of disease. PATIENTS AND METHOD: The consensus diagnostic criteria established by the American Thoracic Society/European Respiratory Society were followed. The study included 16 patients, 10 men (65%) and 6 women (35%), all diagnosed with NSIP by open lung biopsy. Patients were questioned on pathological history, occupational or environmental exposure, medicinal drug use, contact with birds, and relationship with smoking. In addition, were recorded symptoms and physical signs, laboratory and respiratory function results, chest X-ray and computerized tomography scan features, fiberbronchoscopy findings and open lung biopsy findings. RESULTS: Eleven patients (69%) -10 men (100%) and one woman (12%) -were smokers: 4 were active and 7 former smokers; 8 (80%) patients had fibrotic NSIP and three (50%) had cellular NSIP. Nine (56%) patients had a medication history, and 5 received chronic non-steroideal anti-inflammatory drug treatment. Occupational exposure to bleach, detergents, and ammonia or chloride products was documented in 6 cases. Three patients had contact with manufactured plastic products and isocyanate inhalation. CONCLUSIONS: Smoking and medication use were prevalent in NSIP patients. Ibuprofen and celecoxib clearly provoked symptoms in one NSIP patient. Further studies are required to clarify the role of detergents, isocyanates and other occupation-related substances as triggering factors.

Histiocitosis de células de Langerhans. Estudio clínico y evolución a largo plazo de 21 pacientes

Fundamento Los datos clinicos de los pacientes con histiocitosis de celulas de Langerhans (HCL) estan bien establecidos; sin embargo, los nuevos metodos diagnosticos, y en especial la evolucion de la enfermedad a largo plazo, cuando existe afeccion pulmonar son menos conocidos. Metodos Se analizan los datos clinicos y evolutivos de una serie de 21 pacientes diagnosticados de HCL en un hospital de referencia durante un periodo de 12 anos. Dieciocho pacientes presentaban afeccion pulmonar. Resultados El diagnostico se realizo en 18 pacientes por estudio anatomopatologico de las muestras de pulmon, bien por biopsia pulmonar quirurgica en 8 pacientes, o bien por biopsia transbronquial en cuatro; mediante biopsia osea se diagnosticaron 6 pacientes. Los otros pacientes se diagnosticaron por muestras del lavado broncoalveolar (LBA). El estudio de los anticuerpos CD1 en el LBA (> 5% del total de celulas) fue positivo en los 4 pacientes a quienes se practico. Se detecto linfocitopenia en el 28%, mientras que no se detecto disminucion de la hipersensibilidad cutanea retardada en ninguno de los pacientes en que se determino. Tras un seguimiento promedio de 12,8 anos (limites: 4-22 anos), de los 18 pacientes a quienes se pudo realizar el seguimiento, 7 habian fallecido, 6 mostraban afeccion pulmonar funcional moderada o grave, mientras que 5 pacientes no presentaban afeccion pulmonar funcional Conclusion El diagnostico de HCL se ha facilitado con la deteccion de los marcadores inmuno-logicos e histoquimicos introducidos recientemente. En este estudio no se detecto anergia o hi-poergia de las pruebas cutaneas de hipersensibilidad retardada. La evolucion de los pacientes a largo plazo, cuando existe afeccion pulmonar, es desfavorable.

Platelet Thromboembolism after Lung Transplantation

Lung transplant patients have an increased risk of pulmonary embolism which is often associated with hypercoagulability disorders. We present a case of sudden death resulting from pulmonary intravascular platelet thromboembolism following a single-lung transplant.