Comparison of daily anti-hypertensive effects of amlodipine and nifedipine coat-core using ambulatory blood pressure monitoring - utility of "hypobaric curve" and "hypobaric area".

When selecting anti-hypertensives, most physicians do not consider daily blood pressure (BP) variation. To evaluate the effectiveness of anti-hypertensives on the temporal profile of BP, we proposed three new parameters obtained by ambulatory BP monitoring and evaluated these parameters by comparing 5 mg of amlodipine and 40 mg of nifedipine coat-core. Hypobaric values were determined by subtracting BP data collected before administration of the drug from those collected after drug treatment at the corresponding time of day. The hypobaric curve was drawn by plotting the hypobaric values in chronological order, with the time at which the drug was taken set as the starting point. The hypobaric area was the area encircled between the 0 mmHg level line and the hypobaric curve. For amlodipine, the hypobaric areas of systolic blood pressure (SBP) and diastolic blood pressure (DBP) were -19,110 mmHg/min and -10,695 mmHg/min, respectively. Systolic BP decreased -13.3 mmHg, and DBP BP -7.4 mmHg as daily averages. For nifedipine coat-core, the hypobaric areas of SBP and DBP were -32,235 mmHg/min and -18,150 mmHg/min, respectively. Systolic BP decreased -22.3 mmHg and DBP -12.6 mmHg as daily averages. From the hypobaric curves, the trough-to-peak ratios of amlodipine and nifedipine coat-core were measured as 0.67 and 0.60, respectively. The total anti-hypertensive power of nifedipine coat-core, measured by the hypobaric area, was 1.69 times more potent than that of amlodipine. These parameters seem to be useful for evaluating the daily temporal profile of the BP-lowering effects of anti-hypertensive drugs.

Paraneoplastic nephrotic syndrome in patients with lung cancer.

Paraneoplastic nephrotic syndrome has been reported in various malignancies: malignant lymphoma, colon cancer, lung cancer, and prostate cancer. Of these, lung cancer is the most commonly associated with the syndrome. Here, we report 4 cases of nephrotic syndrome associated with lung cancer, in one of which urinary protein and edema were improved by steroid therapy. These results suggest that in patients with paraneoplastic nephrotic syndrome histologically diagnosed as having minimal change disease (MCD), it is important not only to treat the cancer itself but also to use steroids as early as possible. On the other hand, our results also showed that treatment is still difficult for locally advanced or metastatic tumors. Therefore, when we encounter patients with nephrotic syndrome, it is important to be aware of the association of nephrotic syndrome and lung cancer.

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.

Giant cell lung carcinoma in a man with acquired immunodeficiency syndrome.

A 66-year-old man, who was discovered to have human immunodeficiency virus (HIV) infection 22 months previously and was treated with highly active antiretroviral (HAART) therapy, developed giant cell carcinoma of the lung. In English literature, this is the first case of such cell type of lung cancer during HAART therapy. Since giant cell carcinoma of the lung occurs mainly in elderly men who smoke heavily, there may not be a possibility that the HIV or HAART was causative in our patient.

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.

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.

Pulmonary sequestration with elevated serum level of progastrin-releasing peptide.

A 74-year-old woman with rheumatoid arthritis was referred for a mass incidentally noted on chest radiograph. Chest CT scan showed cystic lesions in the right lower lobe. The lesion was evaluated as bronchiectasis, and she was followed up. Three years after the initial presentation, the appearance of the lesion had changed significantly and an elevated air-fluid level in the cystic structures was shown on chest CT scan. The preoperative serum progastrin-releasing peptide (proGRP) level was elevated (108.0 pg/ml; normal: <50 pg/ml). Histopathological specimen obtained by standard lower lobectomy confirmed that the lesion was an intralobar pulmonary sequestration. In the resected lobe, there was no malignant finding, but there were neuroendocrine tumorlet cells, which were positive for proGRP. One month after the resection, the serum proGRP level returned to normal. No pulmonary sequestration with high levels of proGRP has been reported, and this is the first case with elevated serum levels of proGRP.

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.

Malignant meningitis secondary to lung adenocarcinoma: an unusual relapse.

We describe a 64-year-old man with locally advanced lung adenocarcinoma who had meningeal relapse soon after the completion of intensive chemo-radiotherapy. Diagnosis of the malignant meningitis was established by cytological examination of the cerebrospinal fluid, which showed malignant cells consistent with adenocarcinoma from the primary site. Although very rare, it is possible that successful chemo-radiotherapy for locally advanced lung cancer could not prevent malignant meningitis as observed in our patient. Physicians should consider performance of brain MRI or contrast CT of the brain and a lumbar puncture to exclude the diagnosis of malignant meningitis, an uncommon but devastating complication of malignancy.

Overexpression of GATA-3 protects against the development of hypersensitivity pneumonitis.

RATIONALE: Hypersensitivity pneumonitis (HP) is mediated by a Th1 immune response. Transcription factor GATA binding protein-3 (GATA-3) is believed to be a key regulator of Th2 differentiation and thus might play regulatory roles in the pathogenesis of hypersensitivity pneumonitis (HP). OBJECTIVES: We examined the effect of GATA-3 overexpression on the development of HP in mice. METHODS: Wild-type C57BL/6 mice and GATA-3-overexpressing mice of the same background were used in this study. HP was induced by repeated exposure to Saccharopolyspora rectivirgula, the causative antigen of farmer's lung. MEASUREMENTS AND MAIN RESULTS: Antigen exposure resulted in a marked inflammatory response with enhanced pulmonary expression of T-bet and the Th1 cytokine interferon (IFN)-gamma in wild-type mice. The degree of pulmonary inflammation was much less severe in GATA-3-overexpressing mice. The induction of T-bet and IFN-gamma genes was suppressed, but a significant induction of Th2 cytokines, including IL-5 and IL-13, was observed in the lungs of GATA-3-overexpressing mice after antigen exposure. Supplementation with recombinant IFN-gamma enhanced lung inflammatory responses in GATA-3-overexpressing mice to the level of wild-type mice. Because antigen-induced IFN-gamma production predominantly occurred in CD4+ T cells, nude mice were transferred with CD4+ T cells from either wild-type or GATA-3-overexpressing mice and subsequently exposed to antigen. Lung inflammatory responses were significantly lower in nude mice transferred with CD4+ T cells from GATA-3-overexpressing mice than in those with wild-type CD4+ T cells, with a reduction of lung IFN-gamma level. CONCLUSIONS: These results indicate that overexpression of GATA-3 attenuates the development of HP by correcting the Th1-polarizing condition.

A long-term survivor with pulmonary large-cell neuroendocrine carcinoma.

Pulmonary large-cell neuroendocrine carcinoma (LCNEC) has been characterized by highly aggressive behavior, with early spread to both regional lymph nodes and distant sites and a rapidly fatal course. In fact, no reports have described an advanced pulmonary LCNEC patient who has had long-term survival. A patient with large-sized pulmonary LCNEC, who is free of disease 11 years after surgery and postoperative chemotherapy, was reported.

Co-morbid illnesses in patients with respiratory disease.

With the rising age, more patients will be diagnosed with one or more other serious illnesses. This study was undertaken to evaluate the frequency of co-morbid illnesses in patients with respiratory diseases, and to compare the frequency between the elderly and the younger patients. We performed chart review of 2764 patients with respiratory disease who admitted in three hospitals in Japan between January 1990 and March 2005. Co-morbid illnesses were observed in 69.5% of 2764 patients with respiratory disease. In 1150 patients 70 years or older, 83.9% of them had co-morbid illnesses. The prevalence of co-morbid illnesses in patients with respiratory disease clearly rose with increasing age (p= 0.0001), the largest increase occurring after the age of 50. Charlson index in patients with respiratory disease clearly rose with increasing age (p= 0.0001). In both elderly (>or= 70 years) or younger (< 70 years) groups of patients, co-morbid illnesses did not influence on the choice of diagnostic procedure. Although the presence of co-morbid illnesses in our patients with non-malignant respiratory disease did not influence on the choice of treatment, however, the presence of co-morbid illnesses in elderly patients with malignant respiratory disease apparently discouraged the choice of standard therapy. Clinical research should address appropriate therapies not only for the elderly patients without co-morbid illness but also for those with co-morbid illnesses. Being aware of the co-morbid illnesses will allow improved management and the planning of appropriate support to a wide range of elderly patients with respiratory disease with important and peculiar needs for care.

Prognostic value of tumor disappearance rate on computed tomography in advanced-stage lung adenocarcinoma.

BACKGROUND: The proportion of tumor disappearance rate (TDR) on conventional computed tomography (CT) is associated with less aggressive biology, and patients with small peripheral adenocarcinoma accompanied by the TDR component showed better prognosis. These findings led us to the idea that even advanced-stage adenocarcinomas with a higher TDR in the primary lesion on CT might suggest slowly progressing cancer. This study was designed to determine the value of the TDR area in the primary site of advanced-stage lung adenocarcinoma with CT and correlate the CT findings with clinical outcome. PATIENTS AND METHODS: In 103 patients with stage IIIB and IV lung adenocarcinoma, CT appearances and clinical data were reviewed retrospectively. Three methods were used in the evaluation of the TDR area: method I, consolidation on mediastinal windows/mass on lung windows > 75% or not; method II, maximum diameter on mediastinal windows/maximum diameter on lung windows (diameter ratio) > 75% or not; and method III, TDR area on lung windows > 25% or not. RESULTS: In univariate analysis, patients with lung adenocarcinoma with TDR have a more favorable prognosis than those without TDR in all 3 methods (method I, P = 0.001; method II, P = 0.024; method III, P = 0.014; log-rank test). In multivariate analysis, a favorable prognosis in patients with adenocarcinoma with TDR was shown in method I (P = 0.015) and method III (P = 0.006). CONCLUSION: As shown in patients with small peripheral lung adenocarcinoma, those with TDR on CT tended to have a good prognosis in contrast to those without TDR, even in patients with advanced-stage lung adenocarcinoma. Prospective study to confirm these results will be required.