Lung cancer patients with previous or simultaneous the upper aerodigestive cancers.

There have been few reports on clinical characteristics of lung cancer patients with previous or simultaneous upper aerodigestive cancers. To evaluate them, we conducted a retrospective study. The medical records of all lung cancer patients at our division from January 1984 through July 2008 were reviewed. Twenty-one (1.7%) of 1242 patients had previous or simultaneous upper aerodigestive cancers. Twenty patients were smokers. For non-small cell lung cancer (NSCLC), 6 patients underwent surgical resection and 3 were treated with chemotherapy. Three small cell lung cancer (SCLC) patients had chemotherapy. None of the severe complication related to the comorbidities were observed. The median survival for NSCLC and SCLC patients was 15 and 6 months, respectively. For patients with upper aerodigestive cancers, smoking cessation, a chest radiograph or computed tomography scan at least yearly and swift evaluation of signs or symptoms that are suggestive of lung cancer should be recommended.

Small large-cell neuroendocrine carcinoma in a patient with pulmonary emphysema.

Large-cell neuroendocrine carcinomas (LCNECs) are relatively rare, and most reported occurrences tend to involve relatively large tumors. We report a small LCNEC in a 63-year-old male patient with pulmonary emphysema. The peripheral pulmonary nodule did not have lobulation and spiculation, and it was difficult to establish correct diagnosis before surgery because of its small size and effect of surrounding emphysematous change.

Axillary lymph node metastasis in lung cancer.

STUDY OBJECTIVES: Axillary lymph node metastasis (ALNM) from lung cancer is rare. Its prognosis and effective treatments remain unknown. To evaluate clinicopatholgical characteristics of such lung cancer patients, we performed a retrospective study of them, who had ALNM at the time of initial presentation or developed ALNM in their clinical courses. METHODS: We reviewed the medical records and pathological reports of all patients at our division who had a diagnosis of primary lung cancer from January 1985 through August 2007. RESULTS: Ten (0.75%) of 1,340 patients had ALNM. In eight of them, ALNM was detected at the time of initial diagnosis, and two patients developed ALNM in their clinical courses. Lymphatic metastasis to mediastinum was evident in all patients. Supraclavicular and cervical lymph nodes were involved in five and three patients, respectively. One patient had direct chest wall invasion from the lung. Three patients had distant metastases other than axillary or cervical lymph nodes. Four patients received systemic chemotherapy, and another four patients received palliative chest irradiation or supportive care because of their poor performance status. Median survival time of 8 patients who were diagnosed as having ALNMs at initial presentation was 7 months. CONCLUSIONS: The most likely mechanism for axillary node involvement is intercostal lymphatics via spread from mediastinal lymph node metastasis. Routine palpation of the axillae is recommended if chest wall invasion, mediastinal and/or supraclavicular lymph nodes are found either at initial presentation or at follow-up of patients.

Lung cancer in patients aged 80 years and over.

OBJECTIVES: The purpose of this study is to examine clinical and pathological features, treatment modality approaches in the elderly, especially in patients aged 80 years and older. METHODS: From the databases at two educational hospitals during the period from January 1978 and December 2007, medical records of lung cancer patients were retrospectively reviewed. The patient population was divided into three age groups: less than 70 years (the <70 age group), 70-79 years (the 70-79 age group), and 80 years or older (the > or =80 age group). Time trends were also studied in two-time intervals: first study period up to 1997, which represents past practice standards, the second study period up to 2007, which represents contemporary practice. RESULTS: Patients aged 80 years and older comprised 7.5% of 2775 consecutive patients with lung cancer, and there was a rapid increase in the proportion of patients aged 80 years or older from the earlier to the later time period. The > or =80 age group had higher proportion of poor performance status (PS) and comorbid disease than the <70 age group and the 70-79 age group. Unchanged proportion of patients with poor PS and advanced disease at presentation were observed in the > or =80 age group. The > or =80 age group was less likely to be subjected to surgery or chemotherapy, and had inferior outcomes when compared with the 70-79 age group and the <70 age group. Survival improvement was not observed in the > or =80 age group. Multivariate analysis showed good PS, early clinical stage and surgery were favorable prognostic factors in the > or =80 age group. CONCLUSION: In order to improve the outcome, detection of early stage lung cancer in patients with good PS and thorough pretreatment evaluation for appropriate treatment are indeed essential even for the > or =80 age group of patients.

Diagnostic procedures for small pulmonary nodules detected by mass-screening.

BACKGROUND: A retrospective study was performed to evaluate the diagnostic procedures performed in small peripheral pulmonary nodules that were detected at mass screening. PATIENTS AND METHODS: The medical records were reviewed of patients who had peripheral pulmonary nodules < or =20 mm detected by mass screening between 1995 and 2007. RESULTS: A total of 41.7% of patients were diagnosed based on pathological findings of specimens obtained by bronchoscopic procedures (bronchoscopy group), while the remainder were diagnosed using specimens obtained by surgical biopsy (surgery group). The median diameter of lung tumors in the bronchoscopy group was 20 mm, while that in the surgery group was 15 mm. Of patients with lung cancer in the bronchoscopy group 22.9% had tumors < or =15 mm, however, 63.8% of patients in the surgery group had tumors < or =15 mm. CONCLUSION: Pulmonary nodules < or =15 mm in diameter found in specimens obtained by bronchoscopic procedures should be diagnosed by surgical biopsy.

Squamous cell carcinoma antigen in lung cancer and nonmalignant respiratory diseases.

STUDY OBJECTIVES: Squamous cell carcinoma antigen (SCC) has been found in elevated amounts in patients with squamous cell lung cancer (SQLC). Elevated levels have also been found among patients with nonsquamous cell lung cancer (NSQLC) and in subjects with nonmalignant pulmonary disease (NMPD). The purpose of the current study was to evaluate SCC levels among a large number of patients with SQLC, NSQLC, and NMPD. Six hundred thirty-nine lung cancer patients, including 201 SQLC patients and 299 patients with NMPD, who were diagnosed at our hospital up to 2006 were entered. Serum SCC levels were measured with a commercially available kit. RESULTS: Elevated levels (>1.5 ng/ml) of SCC were observed in 52.7% of SQLC patients, but in only 14.2% of NSQLC patients. There was a statistically significant difference in positive rate between SQLC and NSQLC patients. None of the NSQLC patients had serum SCC levels greater than 40.0 ng/ml. Among subjects with NMPD, 28.4% had elevated levels of SCC. However, none of the NMPD patients had serum SCC levels greater than 20.0 ng/ml. CONCLUSIONS: Serum levels of SCC can be elevated (<20.0 ng/ml) in some NMPD patients without coexisting SQLC. Patients with NSQLC and NMPD with elevated SCC levels greater than 40 ng/ml may have coexisting SQLC or squamous cell carcinoma in an extrapulmonary site.

Lung cancer patients with previous or simultaneous urologic cancers.

STUDY OBJECTIVES: There have been few reports on clinical characteristics of lung cancer patients with previous or simultaneous urologic cancers. Additionally, it was scarcely reported whether these patients could tolerate standard therapy. To evaluate them, we conducted a retrospective study. METHODS: The records of patients with lung cancer who had previously or simultaneously urological cancers seen in our division between January 1985 and August 2007 were reviewed. RESULTS: During the study period, 1,105 patients with lung cancer were seen at our division. Thirteen (1.2%) had previous or simultaneous urological cancers (11 males). Eleven patients were smokers. The diagnosis of urological cancers preceded the diagnosis of lung cancer in all but three patients, for whom the diagnosis of urologic cancers was made during the workup of primary lung cancer. Histologically, the lung cancers included six squamous cell carcinomas, four adenocarcinomas, and three small cell lung cancers. Four underwent surgical resection. Six were treated with platinum-containing chemotherapy, but none of them developed severe renal toxicity. The median survival following the diagnosis of lung carcinoma for NSCLC patients was 18 months, and for SCLC it was 24 months. The cause of death in the 12 patients who died in the study period was directly related to lung cancer, and recurrence of urological cancers was observed in none of the patients. CONCLUSIONS: For patients with urological cancers, smoking cessation, a chest radiograph or CT scan at least yearly and swift evaluation of signs or symptoms that are suggestive of lung cancer should be recommended.

A re-evaluation of squamous cell carcinoma antigen (SCC) as a serum marker for non-small cell lung cancer.

Squamous cell carcinoma antigen (SCC) is still a widely used tumor marker for monitoring non-small cell lung cancer (NSCLC), although recent reports discourage its routine use because of low sensitivity. This is a study evaluating the efficacy of SCC and CYFRA21-1 in diagnosing NSCLC. A chart review was performed in a university hospital in Japan, covering a period of 10 years, up to October 2004. During the study period, 142 (35.5%) among 400 NSCLC patients diagnosed, received serum assays of both SCC and CYFRA21-1. Elevated SCC and CYFRA21-1 levels were found in 29.6% and 59.2% of patients, respectively. SCC sensitivity was only 13.0% but CYFRA21-1 sensitivity rose to 73.9% in metastatic patients. The adjunct of SCC increased the CYFRA21-1 sensitivity by 6.3% in the overall population and by only 2.2% for patients with metastases. SCC determination should be considered an inefficient method as a potential diagnosing tool for NSCLC patients, and it provides no additional value when used in combination with CYFRA21-1.

Niflumic acid and AG-1478 reduce cigarette smoke-induced mucin synthesis: the role of hCLCA1.

BACKGROUND: Cigarette smoke induces bronchial mucus secretion. However, the mechanism of this induction is still unidentified. In this study, we investigated the role of the putative calcium-activated chloride channel 1 (CLCA1) and its blocker, niflumic acid, in cigarette smoke-induced mucin synthesis both in vivo and in vitro. METHODS AND RESULTS: Sprague-Dawley rats were exposed to cigarette smoke for 4 weeks. The CLCA1, epidermal growth factor receptor (EGFR), and MUC5AC expressions were increased in the trachea and lung tissues. Goblet-cell hyperplasia with marked mucin staining was detected in the tracheal and bronchial epithelium. In the human bronchial epithelial cell line NCI-H292, cigarette smoke solution also induced mucin production as well as the RNA and protein expressions of CLCA1, EGFR, and MUC5AC. Both in vivo and in vitro, the induction of MUC5AC and mucin synthesis were inhibited by niflumic acid, and/or a selective EGFR tyrosine kinase inhibitor, AG-1478. Niflumic acid also blocked the epidermal growth factor-induced MUC5AC and mucin staining in the NCI-H292 cell line. CONCLUSION: Both EGFR and niflumic acid-sensitive chloride channels (probably CLCA1) are dependently affecting the mucin production as a part of a single complex signaling pathway. CLCA1 may be a key signaling member that can be targeted with pharmacologic interventions to treat mucus hypersecretion.

Thymic and pulmonary mucosa-associated lymphoid tissue lymphomas in a patient with Sjögren's syndrome and literature review.

Mucosa-associated lymphoid tissue lymphoma (MALToma) has been reported in several organs. Among MALTomas, thymic and pulmonary MALTomas are rare. The present report describes a patient with Sjögren's syndrome who presented thymic and pulmonary MALTomas. Although the exact pathogenetic relationship between these two tumours is uncertain, it is likely that the underlying immune dysregulation related to Sjögren's syndrome contributed to the occurrence and the unusual manifestation of MALTomas in this patient.

Effect of inhaled steroids on increased collagen synthesis in asthma.

BACKGROUND: We previously reported that sputum levels of procollagen type I C-terminal peptide (PICP), a marker of ongoing collagen type I deposition, are increased in proportion to airway inflammation in asthma patients. OBJECTIVES: In this study, we examined the effect of inhaled corticosteroids on increased collagen synthesis in step 2-4 asthmatics. METHODS: We compared the sputum PICP concentrations of 25 steroid-naive asthmatics, 25 normal volunteers, and 10 subjects with chronic obstructive pulmonary disease. Asthma subjects were also instructed to start fluticasone propionate treatment, and the percentage of forced expiratory volume in 1 s, sputum eosinophil counts, sputum PICP concentrations, and sputum transforming growth factor-beta-positive cell counts before treatment were compared with those 1 month after treatment. RESULTS: Sputum PICP concentrations were detected in the following order: asthma group >or= chronic obstructive pulmonary disease group > control group. Asthma patients showing high sputum PICP belonged to step 4, although there was no correlation between sputum PICP and asthma severity. Treatment with fluticasone propionate not only significantly improved the mean percentage of forced expiratory volume in 1 s (from 66.7 to 87.2%), but also decreased the mean sputum eosinophil counts (from 13.4 to 5.8%), the mean sputum PICP concentrations (from 30.8 to 10.2 ng/ml), and the mean sputum tumor growth factor-beta-positive cells (from 11.3 to 2.8%). Nevertheless, a significant difference in sputum PICP concentrations was still observed between the control group and the steroid-treated asthma group. CONCLUSIONS: The present results suggest that inhaled corticosteroid treatment might reduce sputum indexes of collagen metabolism and eosinophilic inflammation in asthma patients.

Association of phosphodiesterase 4D gene polymorphisms with chronic obstructive pulmonary disease: relationship to interleukin 13 gene polymorphism.

Activation of the cyclic AMP (cAMP) signaling pathway leads to the suppression of inflammation in the airways and relaxation of airway smooth muscle. Intracellular cAMP levels are determined by a balance between the activities of adenylate cyclase and phosphodiesterases. We hypothesized that polymorphisms of the phosphodiesterase 4D (PDE4D) gene activate its protein function which leads to the downregulation of cAMP, resulting in the development of chronic obstructive pulmonary disease (COPD). A case-control study was performed using Japanese (96 COPD patients and 61 controls) and Egyptians (106 COPD patients and 72 controls) to investigate the association between the polymorphisms of the PDE4D gene and the development of COPD. Genotyping of all subjects for SNP7 (dbSNP ID, rs10075508), SNP13 (rs829259) and SNP15 (rs702531) in exon 15 of the PDE4D gene was conducted. Furthermore, the distributions of haplotypes consisting of PDE4D polymorphisms and those of interleukin (IL) 4, IL13 and beta2 adrenoceptor were analyzed. The distribution of SNP13 allele frequencies of the PDE4D gene was significantly different between the COPD and control groups in the Japanese population (p = 0.041). In haplotype analysis, haplotypes composed of PDE4D SNP7 and IL13 +2044 G/A in the Japanese population showed significant difference between the patients and controls (pcorr = 0.00048). Thus, SNP13 and haplotypes, SNP7 G/A and IL13 +2044 G/A, may be useful for predicting COPD susceptibility.

Overexpression of the transcription factor GATA-3 enhances the development of pulmonary fibrosis.

Recent studies have demonstrated that Th2 cytokines, such as interleukin-4 and interleukin-13, enhance fibrotic processes by activating fibroblast proliferation and collagen production, whereas interferon-gamma, a Th1 cytokine, inhibits these processes. Th1 and Th2 cells both differentiate from common T precursor cells, with transcription factor GATA-3 a key regulator of Th2 differentiation. In the present study, therefore, we examined the effects of GATA-3 overexpression on the development of pulmonary fibrosis in a mouse model. Wild-type C57BL/6 mice and GATA-3-overexpressing (GATA-3-tg) mice of the same background were intratracheally treated with bleomycin. The survival rate after bleomycin was significantly decreased in GATA-3-tg mice compared with wild-type mice. The degree of pulmonary fibrosis was much greater in GATA-3-tg mice than in wild-type mice 28 days after bleomycin treatment. Lung interferon-gamma concentration was significantly decreased in GATA-3-tg mice compared with wild-type mice by 7 days after either saline or bleomycin treatment. The concentration of transforming growth factor-beta, a fibrogenic cytokine, was significantly higher in GATA-3-tg mice than in wild-type mice. Exogenous administration of interferon-gamma to GATA-3-tg mice improved the degree of pulmonary fibrosis and thus increased survival. These results indicate that overexpression of GATA-3 enhances the development of pulmonary fibrosis, possibly by reducing interferon-gamma levels in the lung.

Anaerobic bacterial empyema accompanying intrathoracic gas formation in anorexia nervosa.

OBJECTIVE: Intrathoracic gas formation due to anaerobic pleuropulmonary infection is rare. METHOD & RESULTS: We experienced a case of empyema with intrathoracic gas formation by an anaerobic bacterium in a young woman with anorexia nervosa (AN). CONCLUSION: We should therefore be alert to the possibility of serious infection in patients with AN, even when they have few complaints or normal white blood cell counts.

Prospective study of fever and pneumonia after flexible fiberoptic bronchoscopy in older people.

OBJECTIVES: To assess the frequency of fever and pneumonia after fiberoptic bronchoscopy (FOB) in older people and to evaluate increased risk for these two adverse events with increasing age. DESIGN: Prospective study. SETTING: University hospital system. PARTICIPANTS: Three hundred fifty-eight patients, with 165 (46.1%) patients aged 70 and older, undergoing bronchoscopy. MEASUREMENTS: Indications, abnormal bronchoscopic findings, sampling procedures, final diagnosis, and fever and pneumonia after bronchoscopy. RESULTS: With regard to the indication for bronchoscopy and abnormal bronchoscopic findings, there was no statistical difference between elderly patients (> or =70) and younger patients (<70). Procedures such as forceps biopsy, brushing, and curetting were not performed more often in elderly patients, although final diagnosis of lung cancer was significantly more common in the elderly group (P=.002). The overall incidence of fever after FOB was 6.7%, and that of pneumonia after FOB was 5.6%. The patients aged 70 and older had an incidence of fever after FOB of 3.6% and an incidence of pneumonia of 4.2%, which were not higher than those in patients younger than 70. CONCLUSION: Increasing age is not associated with increasing fever and pneumonia after FOB, and chronological age should not be considered a limiting factor in the decision of whether to perform FOB when it is clinically indicated.