Analysis of continuous first-line treatment with docetaxel and carboplatin for advanced non-small cell lung cancer.

The present study aimed to analyze the efficacy and safety of multiple cycles of docetaxel and carboplatin (CBDCA) as a first-line treatment in patients with advanced non-small cell lung cancer (NSCLC). Patients with stage III or IV NSCLC, whose treatment began between July 1999 and February 2003, were retrospectively evaluated. Relatively low doses of docetaxel and CBDCA were administered for as many cycles as possible. The primary outcome assessed was the overall survival (OS) time, and the secondary outcomes included progression-free survival (PFS) time, response rate (RR) and adverse events. The median cycle number was four (range, 2-12). The median OS time was 400 days, and for adenocarcinoma and non-adenocarcinoma, the OS time was 490 and 192 days, respectively. The median PFS time was 176 days and the RR was 66.7%. The main toxicity of the treatment was neutropenia, with grade 3 or 4 neutropenia occurring in 81.0% of patients. Continuous first-line treatment with this regimen may have encouraging effects within a certain group of advanced NSCLC patients, thereby warranting further investigations.

Production and activation of matrix metalloproteinase 7 (matrilysin 1) in the lungs of patients with idiopathic pulmonary fibrosis.

CONTEXT: Idiopathic pulmonary fibrosis (IPF) is characterized by diffuse interstitial inflammation and fibroblast proliferation with accelerated remodeling of extracellular matrix, which result in irreversible destruction of the lung's architecture. OBJECTIVE: To elucidate the production levels, tissue localization, and activation of matrix metalloproteinase 7 (MMP-7) in the lungs of patients with IPF. DESIGN: Bronchoalveolar lavage analysis was performed in 17 IPF patients and 6 healthy volunteers. Levels of MMP-7 in blood were assayed in 23 IPF patients and 20 controls. Histologic and immunohistochemical analyses were performed on paraffin sections of the lung tissues from patients with IPF, interstitial pneumonia associated with rheumatoid arthritis, or nonspecific interstitial pneumonia. RESULTS: The proMMP-7 levels in bronchoalveolar lavage fluids from IPF patients were significantly higher than those from healthy controls, although there was no difference in the serum levels between the 2 groups. By immunohistochemistry, proMMP-7 was localized mainly to the hyperplastic alveolar and metaplastic bronchiolar epithelial cells in the lung tissues from IPF patients. Active MMP-7 was immunolocalized on alveolar macrophages and hyperplastic epithelial cells, which were also immunostained with antibody against CD151, a molecule associated with activation of proMMP-7. Immunoblot analysis indicated the overproduction of proMMP-7 together with a small amount of active MMP-7 in bronchoalveolar lavage fluids from IPF patients. The MMP-7 activity was detected in a cross-linked carboxymethylated transferrin film assay. CONCLUSIONS: proMMP-7 is excessively produced by hyperplastic alveolar and metaplastic bronchiolar epithelial cells and activated locally in the lungs of IPF patients, suggesting that MMP-7 may contribute to the pathology of IPF.

Macrophage derived chemokine (CCL22), thymus and activation-regulated chemokine (CCL17), and CCR4 in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronically progressive interstitial lung disease of unknown etiology. Previously, we have demonstrated the selective upregulation of the macrophage-derived chemokine CCL22 and the thymus activation-regulated chemokine CCL17 among chemokines, in a rat model of radiation pneumonitis/pulmonary fibrosis and preliminarily observed an increase in bronchoalveolar (BAL) fluid CCL22 levels of IPF patients. METHODS: We examined the expression of CCR4, a specific receptor for CCL22 and CCL17, in bronchoalveolar lavage (BAL) fluid cells, as well as the levels of CCL22 and CCL17, to elucidate their pathophysiological roles in pulmonary fibrosis. We also studied their immunohistochemical localization. RESULTS: BAL fluid CCL22 and CCL17 levels were significantly higher in patients with IPF than those with collagen vascular diseases and healthy volunteers, and there was a significant correlation between the levels of CCL22 and CCL17 in patients with IPF. CCL22 levels in the BAL fluid did not correlate with the total cell numbers, alveolar lymphocytes, or macrophages in BAL fluid. However, the CCL22 levels significantly correlated with the numbers of CCR4-expressing alveolar macrophages. By immunohistochemical and immunofluorescence analysis, localization of CCL22 and CCR4 to CD68-positive alveolar macrophages as well as that of CCL17 to hyperplastic epithelial cells were shown. Clinically, CCL22 BAL fluid levels inversely correlated with DLco/VA values in IPF patients. CONCLUSION: We speculated that locally overexpressed CCL22 may induce lung dysfunction through recruitment and activation of CCR4-positive alveolar macrophages.

[Unexplained pulmonary arterial hypertension in a patient with lung resection, treated with sildenafil and beraprost].

A 70-year-old man with a past history of lung resection for early stage lung cancer was admitted to our hospital because of worsening exertional dyspnea. Right heart catheterization revealed severe pulmonary arterial hypertension (PAH) with pulmonary vascular resistance of 1671.64 dyne.sec.cm(-5). The patient was treated with sildenafil added to an oral prostacyclin analog, beraprost, and long term oxygen therapy. His exertional dyspnea continued to improve until his sudden death following nasal bleeding. Autopsy revealed marked thickening of pulmonary arteriolar walls, but no recurrence of lung cancer, significant pulmonary embolism or pulmonary parenchymal disease. His PAH could not be explained by the mild airway obstruction or sleep apnea syndrome, and unrelated pulmonary vascular disease was suspected.

Sleep disordered breathing in patients with chronic obstructive pulmonary disease.

Sleep-related disordered breathing (SDB) and its influence on desaturation were examined in stable COPD patients with waking SpO2 > 90%. With respiratory inductance plethysmography, thoracic-abdominal respiratory movements for all events with more than 4% desaturation were analyzed in 26 patients. Types of SDB were confirmed by full polysomnography. Irregular breathing induced desaturation, while stable respiration continued during some desaturation events. Three types of altered ventilation were observed: hypoventilation, paradoxical movement and periodic breathing. An unusual type of paradoxical movement, with normal airflow despite progressive desaturation, was observed in REM sleep. Patients were divided into desaturation (15 patients) and non-desaturation (11 patients) groups. Daytime arterial blood gas, lung function values, and 6-min walking distance did not differ. Awake, mode, maximum and minimum nocturnal SpO2 were lower in the desaturation group. SDB-induced desaturation events in the desaturation group were more frequent (9.2+/-3.5 vs. 1.8+/-2.2 times), a greater SpO2 decrease (11.4+/-7.1% vs. 5.2+/-2.1%) and longer duration (73.2+/-34.8 vs. 18.8+/-39.0 min). Patterns of SDB in the desaturation group were hypoventilation (74.4+/-23.4%), paradoxical movement (10.2+/-14.5%), periodic breathing (12.1+/-18.3%) and unclassified (5.8+/-11.2%). These results reveal that lower SpO2 and SDB influence nocturnal desaturation in stable COPD patients.

[A case of acute exacerbation of desquamative interstitial pneumonia after video-assisted thoracoscopic surgery (VATS)].

A 70-year-old man in whom nodular and reticular shadows had been noted on chest radiography since 1992 was admitted to our hospital with complaints of persistent cough and dyspnea on exertion in August, 2000. The definitive diagnosis of lung abnormalities was not confirmed by TBLB. He was re-admitted to our hospital to undergo a lung biopsy by video-assisted thoracoscopic surgery. Although desquamative interstitial pneumonia was diagnosed, respiratory failure developed rapidly after surgery. He responded well to high-dose steroid administration followed by maintenance therapy with a moderate dose of steroid, resulting in a considerable importance of the clinical condition associated with a significant decrease in the ground-glass opacities and infiltrative shadows. Although we could find no literature reporting acute exacerbation of DIP, our case demonstrates that DIP may also be acutely exacerbated when a severe insult is superimposed.

[A case of stage IV primary lung cancer with no metastasis except in the choroid plexus].

A 69-year-old man become aware of myiodesopsia. He visited the Department of Ophthalmology at Keio University Hospital and choroidal metastasis of the right eye was diagnosed. A tumor shadow was detected in the lower lobe of the left lung on chest radiographs, and the serum CEA concentration was found to be significantly increased. Through bronchoscopic examinations, he was confirmed to have primary lung cancer (histological classification: adenocarcinoma). Although detailed systemic examinations were performed, no metastasis to lymph nodes or distant organs except the choroid plexus was detected, which is very rare in a case of stage IV primary lung cancer. In conclusion, it is suggested to be very important to look for ophthalmological abnormalities, even in the case of apparently early lung cancer that seems to be resectable.