Clinical Significance of ABCG2 Haplotype-tagging Single Nucleotide Polymorphisms in Patients With Unresectable Non-Small Cell Lung Cancer Treated With First-line Platinum-based Chemotherapy.

OBJECTIVES: The ATP-binding cassette (ABC) ABCG2, involved in multidrug resistance (MDR) in cancer cells, plays an integral role in drug resistance. Single nucleotide polymorphisms (SNPs) have been identified in many MDR-associated ABC genes that seem to influence drug sensitivity/resistance through various mechanisms. Therefore, we investigated whether ABCG2 haplotype-tagging SNPs (htSNPs) were associated with clinical outcomes in patients with unresectable non-small cell lung cancer (NSCLC) treated with front-line platinum-based chemotherapy. PATIENTS AND METHODS: We genotyped 4 ABCG2 htSNPs for 129 unresectable NSCLC cases treated with first-line platinum-based chemotherapy. Clinical characteristics, treatment outcomes, and predictive value of the htSNPs in patient response, survival, and adverse events related to platinum-based chemotherapy were analyzed according to each ABCG2 htSNP using the χ test, Kaplan-Meier method, and Cox proportional hazard model. RESULTS: The rs2725264 was significantly related to overall survival (OS) (P=0.018, log-rank test). The median survival duration (in months) for patients with the rs2725264 T/T, T/C, and C/C genotypes was 35.75 (95% confidence interval [CI], 24.25-47.25), 34.25 (hazard ratio [HR] 1.27 [0.68 to 2.35]; 95% CI, 27.16-41.34), and 14.89 (HR 3.22 [1.26 to 8.24], 95% CI, 13.86-15.92), respectively. The rs2725264 was identified as an independent factor by Cox proportional hazard model analysis (P=0.028). In the taxane-based groups, OS was associated with rs2725264 (P=0.041), whereas in the gemcitabine-based groups, OS was associated with rs4148149 (P=0.014). CONCLUSIONS: Our data suggest ABCG2 htSNPs rs2725264 (overall group and taxane-platinum combination group) and rs4148149 (gemcitabine-platinum combination group) were associated with OS in unresectable NSCLC patients treated with first-line platinum-based chemotherapy. Thus, the ABCG2 htSNP rs2725264 may be independently associated with OS in unresectable NSCLC patients treated with first-line platinum-based chemotherapy.

Risk factors for latent tuberculosis infection in close contacts of active tuberculosis patients in South Korea: a prospective cohort study.

BACKGROUND: The diagnosis and treatment of latent tuberculosis infection (LTBI) have become mandatory to reduce the burden of tuberculosis worldwide. Close contacts of active TB patients are at high risk of both active and LTBI. The aim of this study is to identify the predominant risk factors of contracting LTBI, persons in close contact with TB patients were recruited. This study also aimed to compare the efficacy of the tuberculin skin test (TST) and QuantiFERON(®)-TB GOLD (QFT-G) to diagnose LTBI. METHODS: Close contacts of active pulmonary TB patients visiting a hospital in South Korea were diagnosed for LTBI using TST and/or QFT-G. The association of positive TST and/or QFT-G with the following factors was estimated: age, gender, history of Bacillius Calmette-Guerin (BCG) vaccination, history of pulmonary TB, cohabitation status, the acid-fast bacilli smear status, and presence of cough in source cases. RESULTS: Of 308 subjects, 38.0% (116/305) were TST positive and 28.6% (59/206) were QFT-G positive. TST positivity was significantly associated with male gender (OR: 1.734; 95% CI: 1.001-3.003, p =0.049), history of pulmonary TB (OR: 4.130; 95% CI: 1.441-11.835, p =0.008) and household contact (OR: 2.130; 95% CI: 1.198-3.786, p =0.01) after adjustment for confounding variables. The degree of concordance between TST and QFT-G was fair (70.4%, κ =0.392). CONCLUSIONS: A prevalence of LTBI among close contacts of active pulmonary TB patients was high, and prior TB history and being a household contact were risk factors of LTBI in the study population.

Factors influencing pleural adenosine deaminase level in patients with tuberculous pleurisy.

BACKGROUND: Adenosine deaminase (ADA) activity is useful for diagnosing tuberculous (TB) pleurisy in regions with a high prevalence of tuberculosis. However, some cases of TB pleural effusion show decreased ADA activity. Therefore, we evaluated factors influencing pleural ADA levels in patients with TB pleurisy. METHODS: We retrospectively evaluated 182 patients with TB pleural effusion who were admitted to Gyeongsang National University Hospital from January 2004 to September 2008. Patients were dichotomized into 2 groups: a low-ADA (<40 IU/L) group (n = 22) and a high-ADA (≥40 IU/L) group (n = 160). Age, sex, ADA level of pleural effusion, smoking status, history of tuberculosis and comorbid diseases were evaluated in each group. RESULTS: The median age of the patients was 50.5 years, with a male to female ratio of 1.72:1. Patients with a low-ADA level were significantly older than those with a high ADA level (66.9 ± 12.0 versus 49.4 ± 21.2 years, P < 0.001). A history of tuberculosis and hypertension was more common in the low-ADA group than in the high-ADA group (31.8% versus 15.0%, P = 0.049 and 36.4% versus 16.9%, P = 0.03, respectively). A multivariate analysis revealed that older age and current smoking were predictive of TB pleurisy with a low ADA level (odds ratios, 1.053 and 4.848; P = 0.002 and 0.028, respectively). CONCLUSIONS: Physicians should be careful when interpreting pleural ADA levels in elderly patients and/or current smokers for the diagnosis of TB pleurisy.

Increased plasma osteopontin in frequent exacerbator and acute exacerbation of COPD.

INTRODUCTION: Osteopontin (OPN) is a phosphorylated glycoprotein expressed by diverse tissues including bone, brain, kidney, liver and lung. Limited data exist regarding OPN in chronic obstructive pulmonary disease (COPD) and the exacerbation of this condition. OBJECTIVES: The aim of this study was to evaluate plasma OPN levels and investigate the clinical usefulness of plasma OPN measurement in patients with COPD. METHODS: Plasma OPN levels were measured and compared in patients with COPD exacerbation (n = 64), patients with stable COPD (n = 68) and healthy controls (n = 30). In patients with COPD exacerbation, plasma OPN levels were measured repeatedly in convalescence. Patients with stable COPD were categorized into frequent and infrequent exacerbators according to their frequency of exacerbation, and plasma OPN levels were compared between these two groups. Plasma OPN levels were determined by enzyme-linked immunosorbent assay. RESULTS: Patients with COPD exacerbation had increased plasma OPN levels compared with those with stable COPD and healthy controls (32.6 ± 29.6, 17.6 ± 11.1, 8.4 ± 6.1 ng/mL, respectively; P < 0.001). In patients with COPD exacerbation, plasma OPN levels were significantly decreased in convalescence (44.8 ± 43.5 vs 24.6 ± 13.6 ng/mL; P = 0.034). Frequent exacerbators had higher plasma OPN levels compared with infrequent exacerbators (22.5 ± 12.0 vs 15.0 ± 9.8 ng/mL; P = 0.008). CONCLUSIONS: Plasma OPN levels were increased in patients with COPD exacerbation and frequent exacerbators, which suggests a possible role for OPN as a biomarker of COPD exacerbation.

Phase II trial of biweekly chemotherapy with docetaxel and cisplatin in high-risk patients with unresectable non-small cell lung cancer.

PURPOSE: We investigated the efficacy and toxicity of a biweekly schedule of docetaxel and cisplatin in high-risk patients with unresectable (stages IIIB-IV) non-small cell lung cancer (NSCLC). METHODS: In this study, 48 high-risk patients with previously untreated locally advanced or metastatic NSCLC were treated with combination chemotherapy consisting of docetaxel 40 mg/m(2) and cisplatin 40 mg/m(2); both drugs were given biweekly, on days 1 and 15, every 4 weeks in an outpatient setting. RESULTS: Complete response, partial response, and stable disease were observed in 1 (2.1%), 30 [62.5%, 95% confidence interval (CI) 47.9-77.1], and 4 (8.3%) patients. The median overall survival was 15.1 months (95% CI 11.7-18.5) and the median time to progression was 7.5 months (95% CI 6.4-8.6). The major toxicity was grade 3 anemia in 7 (14.6%) patients. Grade 3/4 neutropenia was observed in 5 (10.4%) patients. Among the nonhematologic toxicities, grade 3 infection and grade 3 diarrhea were observed in 5 (10.4%) and 4 (8.3%) patients, respectively. No treatment-related mortality was found. CONCLUSIONS: As a front-line chemotherapy for high-risk patients with unresectable NSCLC in an outpatient setting, the biweekly schedule of docetaxel and cisplatin showed feasible efficacy with acceptable hematologic toxicities, comparable to the results of previous studies of triweekly or weekly schedules. Additional large randomized studies are needed to optimize the schedule and dosage of combination therapy with docetaxel and cisplatin in high-risk patients with unresectable NSCLC.

Association between weight change and clinical outcomes in critically ill patients.

PURPOSE: Body weight fluctuates daily throughout a patient's stay in the intensive care unit (ICU) due to a variety of factors, including fluid balance, nutritional status, type of acute illness, and presence of comorbidities. This study investigated the association between change in body weight and clinical outcomes in critically ill patients during short-term hospitalization in the ICU. METHODS: All patients admitted to the Gyeongsang National University hospital between January 2010 and December 2011 who met the inclusion criteria of age 18 or above and ICU hospitalization for at least 2 days were prospectively enrolled in this study. Body weight was measured at admission and daily thereafter using a bed scale. Univariate and multivariate linear and logistic regression analyses were performed to evaluate factors associated with mortality and the association between changes in body weight and clinical outcomes, including duration of mechanical ventilation (MV) use, length of ICU stay, and ICU mortality. RESULTS: Of the 140 patients examined, 33 died during ICU hospitalization, yielding an ICU mortality rate of 23.6%. Non-survivors experienced higher rates of severe sepsis and septic shock and greater weight gain than survivors on days 2, 3, 4, 5, and 6 of ICU hospitalization (P < .05). Increase of body weight on days 2 through 7 on ICU admission was correlated with the longer stay of ICU, and increase on days 3 through 7 on ICU admission was correlated with the prolonged use of mechanical ventilation. Increase of body weight on days 3 through 5 on ICU admission was associated with ICU mortality. CONCLUSIONS: Increase in body weight of critically ill patients may be correlated with duration of mechanical ventilation use and longer stay of ICU hospitalization and be associated with ICU mortality.

Value of cytologic analysis of bronchial washings in lung cancer on the basis of bronchoscopic appearance.

INTRODUCTION: We evaluated the diagnostic yield of cytologic analysis of bronchial washing in addition to forceps biopsy on the basis of bronchoscopic appearance and histologic type in lung cancer. METHODS: This retrospective study included 611 patients who had lung cancer and underwent bronchoscopic procedures between April 2003 and December 2008. Bronchoscopic appearance was classified into six types (tumor, infiltrative, necrotic, normal, compressive and aspecific) on the basis of endoscopic morphology. RESULTS: The forceps biopsy were positive in 492 cases (80.5%), and the diagnostic yield of the combination of forceps biopsy with cytologic analysis of bronchial washing was 84.1% (514/611 cases), that is, a statistically significant increase of 3.6% (P < 0.001). Washing cytologic analysis in the case of tumor, infiltrative and necrotic lesions had higher diagnostic yields than that in the case of normal, compressive and aspecific lesions (41.7% vs 29.3%), but its diagnostic yield did not increase on combination with forceps biopsy (P > 0.05). However, in the case of normal and compressive lesions, the addition of forceps biopsy to washing cytologic analysis significantly increased the diagnostic yield (P < 0.05). The histologic type of lung cancer did not significantly affect the difference in diagnostic yield between forceps biopsy alone and the combination of forceps biopsy and washing cytologic analysis (P > 0.05). CONCLUSIONS: The combination of forceps biopsy and washing cytologic analysis offers a better diagnostic yield than biopsy alone in diagnosing lung cancer. Both procedures should be performed during bronchoscopy even if no endobronchial lesion is present.

Clinical Features according to the Frequency of Acute Exacerbation in COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is now regarded as a heterogenous disease, with variable phenotypes. Acute exacerbation of COPD is a major event that alters the natural course of disease. The frequency of COPD exacerbation is variable among patients. We analyzed clinical features, according to the frequency of acute exacerbation in COPD. METHODS: Sixty patients, who visited Gyeongsang National University Hospital from March 2010 to October 2010, were enrolled. Patients were divided into two groups, according to their frequency of acute exacerbation. Frequent exacerbator is defined as the patient who has two or more exacerbation per one year. We reviewed patients' medical records and investigated modified Medical Research Council (MMRC) dyspnea scale, smoking history and frequency of acute exacerbation. We also conducted pulmonary function test and 6-minute walking test, calculated body mass index, degree of airway obstruction and dyspnea and exercise capacity (BODE) index and measured CD146 cells in the peripheral blood. RESULTS: The number of frequent exacerbators and infrequent exacerbators was 20 and 40, respectively. The frequent exacerbator group had more severe airway obstruction (forced expiratory volume in one second [FEV(1)], 45% vs. 65.3%, p=0.001; FEV(1)/forced vital capacity, 44.3% vs. 50.5%, p=0.046). MMRC dyspnea scale and BODE index were significantly higher in the frequent exacerbator group (1.8 vs. 1.1, p=0.016; 3.9 vs. 2.1, p=0.014, respectively). The fraction of CD146 cells significantly increased in the frequent exacerbator group (2.0 vs. 1.0, p<0.001). CONCLUSION: Frequent exacerbator had more severe airway obstruction and higher symptom score and BODE index. However, circulating endothelial cells measured by CD146 needed to be confirmed in the future.

Clinical significance of ERCC2 haplotype-tagging single nucleotide polymorphisms in patients with unresectable non-small cell lung cancer treated with first-line platinum-based chemotherapy.

BACKGROUND: First-line platinum-based chemotherapy is currently considered the standard treatment for unresectable non-small cell lung cancer (NSCLC). However, resistance to platinum-based chemotherapy results in poor prognoses. The DNA repair pathway is a crucial molecular mechanism potentially involved in resistance to platinum-based chemotherapy. ERCC2 plays an integral role in the nucleotide excision repair pathway. Furthermore, single nucleotide polymorphisms (SNPs) and haplotypes in the ERCC2 gene are thought to be associated with the risk of developing lung cancer and clinical outcomes. Therefore, we evaluated the impact of ERCC2 haplotype-tagging SNPs (htSNPs) on the clinical parameters of first-line platinum-based chemotherapy in unresectable NSCLC. PATIENTS AND METHODS: We genotyped 8 ERCC2 htSNPs for 129 unresectable NSCLC (stage IIIA, 12; stage III, 36; stage IV, 82) cases treated with first-line platinum-based chemotherapy. Clinical characteristics, treatment outcomes, hematological and non-hematological toxicities, and predictive value of the htSNPs in patient response, survival, and adverse events related to platinum-based chemotherapy were analyzed according to each ERCC2 htSNP using the chi-square test, Kaplan-Meier method, and Cox proportional hazard model. RESULTS: No differences were observed in patient or disease characteristics and response according to ERCC2 htSNPs. In a survival analysis, rs50872 was significantly related to overall survival (OS) (log-rank test, p=0.014). The median survival duration of rs50872 G/G, A/G, and A/A genotypes was 35.75 (95% confidence interval [CI] 21.05-50.45), 36.07 (hazard ratio [HR] 1.02, 95% CI 25.20-46.94), and 16.75 (HR 3.49, 95% CI 5.73-27.77) months, respectively. A significant association was observed between grades 3 and 4 infections and poor survival: OS in patients with a grade 0-2 infection: 35.75 months (95% CI 28.15-43.35); OS in patients with a grade 3-4 infection: 12.86 months (95% CI 8.99-16.72, HR 3.57) (log-rank test, p<0.001). In a subgroup analysis based on taxane-platinum vs. gemcitabine-platinum doublets, the rs238405 genotype was significantly related to OS in the taxane-platinum doublets group. However, the rs238416 genotype was significantly associated with OS in the gemcitabine-based group. CONCLUSIONS: ERCC2 htSNPs rs50872 (overall), rs238405 (taxane-platinum doublets group), and rs238416 (gemcitabine-platinum doublets group) and infection related to first-line chemotherapy were associated with OS in unresectable NSCLC patients treated with first-line platinum-based chemotherapy. However, additional large prospective studies focusing on the role of ERCC2 htSNPs in unresectable NSCLC are needed.

A case of isoniazid-induced thrombocytopenia: recovery with immunoglobulin therapy.

Treatment for a 51-year-old man with pulmonary tuberculosis was initiated with isoniazid, rifampicin, ethambutol, and pyrazinamide, and discontinued after 3 weeks because of skin rash and itchiness. Isoniazid monotherapy was restarted after 2 weeks. Two days later, the platelet count decreased from 150 to 4×10(3)/mm(3). Despite platelet transfusion and oral corticosteroid treatment, the platelet count did not recover. However, after a 2-day administration of intravenous immunoglobulin, the platelet count recovered to 209×10(3)/mm(3). This report describes a case of isoniazid-induced thrombocytopenia that was reversed with intravenous immunoglobulin, thus highlighting the efficacy of this treatment for this rare condition.

Hypoxia-inducible factor-1α and excision repair cross-complementing 1 in patients with small cell lung cancer who received front-line platinum-based chemotherapy: a retrospective study.

INTRODUCTION: Hypoxia-inducible factor-1α (HIF-1α), which plays an essential role in the adaptive response of cells to hypoxia, is associated with aggressive tumor behavior. Furthermore, a relationship between excision repair cross-complementing 1 (ERCC1) expression and platinum resistance has been reported in patients with various malignancies. The aim of this study was to investigate the expression of HIF-1α and ERCC1 and to elucidate the clinical significance of their expression in patients with small cell lung cancer (SCLC) treated with front-line platinum-based chemotherapy. METHODS: SCLC biopsy samples were obtained before front-line platinum-based chemotherapy from 111 patients with SCLC (limited disease, 29; extensive disease [ED], 82) between January 2002 and December 2009 at Gyeongsang National University Hospital. The expression levels of HIF-1α and ERCC1 were assessed by immunohistochemistry. RESULTS: High expression levels of ERCC1 and HIF-1α were observed in 49 (44.1%) and 71 (64.0%) of 111 patients, respectively. Expression of ERCC1 and HIF-1α was not significantly associated with age, sex, Eastern Cooperative Oncology Group performance status, weight loss, or response to treatment, regardless of stage. In ED-SCLC, low expression in the HIF-1α group showed statistically better survival compared with high expression in the HIF-1α group (p = 0.018). Multivariate analysis revealed that response to front-line platinum-based chemotherapy (p < 0.001), good Eastern Cooperative Oncology Group performance status (0-1) (p = 0.002), and low expression of HIF-1α (p = 0.004) were independent predictors of better overall survival in ED-SCLC. CONCLUSIONS: Low expression of HIF-1α may be a useful predictor of better overall survival in ED-SCLC patients treated with front-line platinum-based chemotherapy.

Endobronchial aspergilloma: report of 10 cases and literature review.

PURPOSE: A retrospective investigation of the clinical and radiologic features as well as the bronchoscopic appearance was carried out in patients with endobronchial aspergilloma. MATERIALS AND METHODS: Ten patients with endobronchial aspergilloma diagnosed by bronchoscopy and histological examination were identified at the Gyeongsang University Hospital of Korea, from May 2003 to May 2009. RESULTS: The patients included 9 men and 1 woman, and the age of the patients ranged from 36 to 76 (median, 58 years). The associated diseases or conditions were: previous pulmonary tuberculosis in 7 patients, lung cancer in 2 patients, pulmonary resection in 1 patient, and foreign body of the bronchus in 1 patient. The chest radiologic finding showed fibrotic changes as a consequence of previous tuberculosis infection in 6 patients and a mass-like lesion in 2 patients. Two patients had a co-existing fungus ball, and an endobronchial lesion was suspected in only 2 patients on the CT scan. The bronchoscopic appearance was a whitish to yellow necrotic mass causing bronchial obstruction in 7 patients, foreign body with adjacent granulation tissue and whitish necrotic tissue in 1 patient, whitish necrotic tissue at an anastomosis site in 1 patient, and a protruding mass with whitish necrotic tissue in 1 patient. CONCLUSION: An endobronchial aspergilloma is a rare presentation of pulmonary aspergilosis and is usually incidentally found in immunocompetent patients with underlying lung disease. It usually appears as a necrotic mass causing bronchial obstruction on bronchoscopy and can be confirmed by biopsy.

Serum angiopoietin-2 levels are elevated during acute exacerbations of COPD.

BACKGROUND AND OBJECTIVE: Recently, angiopoietin-2 (Ang-2) was identified as a ligand of the endothelial receptor tyrosine kinase, Tie-2. Ang-2 is an angiopoietin-1 antagonist that plays a role in vascular destabilization and remodelling, which may increase in some diseases. However, serum Ang-2 levels have not been evaluated in patients with COPD. In this study, we examined serum Ang-2 concentrations in patients experiencing COPD exacerbations and in patients with stable COPD. METHODS: Serum samples were obtained from 49 patients experiencing COPD exacerbations, 22 patients with stable COPD and 18 healthy control subjects. Serum Ang-2 concentrations were measured by ELISA. RESULTS: Serum Ang-2 concentrations were significantly higher in patients with acute exacerbations of COPD than in those with stable COPD or control subjects, and were significantly positively correlated with serum CRP levels but inversely correlated with PaO(2) in patients with exacerbations. In addition, Ang-2 levels decreased significantly after clinical recovery from the acute exacerbation. CONCLUSIONS: Serum Ang-2 levels are significantly elevated during acute exacerbations of COPD, as compared with stable COPD.

Anti-inflammatory effects of celecoxib in rat lungs with smoke-induced emphysema.

Chronic airway inflammation is a characteristic feature of destructive cigarette smoking (CS)-induced lung disease, particularly in patients with emphysema. Celecoxib, a specific cyclooxygenase-2 (COX-2) inhibitor, is widely used to treat inflammation. However, the exact mechanisms underlying this drug's anti-inflammatory effects have not yet been determined in pulmonary emphysema. Here, we explore whether celecoxib attenuates CS-induced inflammation in rat lungs. Rats were exposed to smoke and received celecoxib via intragastric feeding daily for 20 wk. We found that celecoxib inhibited interalveolar wall distance and pulmonary inflammation in the lungs of CS-treated rats. Celecoxib inhibited serum NO production, iNOS, COX-2 expression, and PGE(2) production in CS-treated lung tissues. Our immunohistochemical data showed that CS-induced CD68 and COX-2 expression were inhibited by celecoxib. Furthermore, celecoxib attenuated the activation of phospho-IkappaBalpha and NF-kappaB in CS-treated rat lung. In addition, there was an inhibitory effect of celecoxib on the COX-2 expression and NF-kappaB activation in LPS-stimulated RAW 264.7 macrophages. Celecoxib also attenuated NF-kappaB activation in COX-2 siRNA-transfected RAW 264.7 macrophages. Thus, our findings suggest that the anti-inflammatory effects of celecoxib are mediated by its effects on NF-kappaB-regulated gene expression, which ultimately reduces the progression of CS-induced pulmonary emphysema.

A case of anaphylaxis after the ingestion of yacon.

Anaphylaxis is a potentially life-threatening systemic allergic reaction, often with an explosive onset; the symptoms range from mild flushing to upper respiratory obstruction, with or without vascular collapse. Foods are common offending allergens and remain the leading cause of outpatient anaphylaxis in most surveys. Yacon (Smallanthus sonchifolius) is a plant native to the Andes region, where its root is cultivated and consumed mainly as food. Unlike most edible roots, yacon contains large amounts of ructooligosaccharides. Traditionally, yacon tubers have been used as a source of natural sweetener and syrup for people suffering from various disorders. We report the case of a 55-year-old woman who developed syncope and generalized urticaria after ingesting yacon roots. The patient had positive skin prick and intradermal tests to yacon extract. An open food challenge test was performed to confirm food anaphylaxis and was positive 10 minutes after the consumption of yacon roots. To our knowledge, this is the first reported case of anaphylaxis after the ingestion of yacon roots.

Phase II study of a biweekly schedule of docetaxel and cisplatin in patients with metastatic non-small cell lung cancer.

PURPOSE: We investigated the efficacy and toxicity of a biweekly schedule of docetaxel and cisplatin in patients with metastatic non-small cell lung cancer (NSCLC). METHODS: In this study, 48 patients with previously untreated metastatic NSCLC were given combination chemotherapy consisting of docetaxel 40 mg/m(2) and cisplatin 40 mg/m(2); both drugs were given biweekly, on days 1 and 15, every 4 weeks. RESULTS: A partial response and stable disease were observed in 25 patients (52.1%, 95% CI: 38.7-66.9%) and ten patients (20.8%), respectively. The overall median survival was 14.0 months (95% CI: 7.10-20.9 months). There was no treatment-related mortality. The major toxicity was grade 2 asthenia (35.4%). Grade 4 neutropenia was observed in two patients (4.2%), as was grade 3 infection (4.2%). CONCLUSIONS: As a front-line chemotherapy in an outpatient setting for patients with metastatic NSCLC, the biweekly schedule of docetaxel and cisplatin showed effective antitumor activity with a marked reduction in hematologic toxicity, comparable to the results of previous studies using 3-week or weekly schedules. Further randomized studies are needed before this can be accepted as a standard schedule.

Temporal changes of angiopoietins and Tie2 expression in rat lungs after monocrotaline-induced pulmonary hypertension.

Angiogenic factors such as vascular endothelial growth factor (VEGF) are implicated in pulmonary hypertension (PH). However, the pathway of angiogenic factor-mediated pathologic angiogenesis in PH remains unclear. In this study, we evaluated the temporal expression of angiopoietin (Ang) 1, Ang2, and their receptor (Tie2) as well as VEGF, endothelial nitric oxide synthase (eNOS), inducible NOS (iNOS), and heme oxygenase 1 (HO1) in the monocrotaline-induced PH model. Histologic evaluation showed pathologic vascular remodeling in the arteries of lung sections 1 wk after monocrotaline treatment. Protein levels of Ang1, Ang2, eNOS, iNOS, HO1, and VEGF were increased 1 wk after monocrotaline treatment but Tie2 protein levels were decreased 2 wk afterward. These results suggest that Ang2 mediates vascular remodeling in PH by decreasing Tie2 expression. Therefore, the Ang-Tie2 system may play a role in the pathophysiology of PH.

Fixed-dose rate infusion of gemcitabine and weekly cisplatin in elderly or poor performance status patients with unresectable non-small cell lung cancer.

PURPOSE: We investigated the efficacy and toxicity of a 4-week schedule of a fixed dose rate infusion of gemcitabine and weekly cisplatin in elderly or poor performance status patients with unresectable non-small cell lung cancer (NSCLC). METHODS: In this study, 48 patients with previously untreated NSCLC were given combination chemotherapy that consisted of gemcitabine 1,000 mg/m(2) (10 mg/m(2)/min fixed dose rate infusion) and cisplatin 25 mg/m(2), and both drugs were given weekly on days 1, 8 and 15. RESULTS: A partial response and stable disease were observed in 20 patients (41.7%, 95% CI; 27.8-55.6%) and 12 patients (25.0%), respectively. The overall median survival was 10.30 months (range: 7.85-12.74 months). Major toxicities included neutropenia (grade 3 to 4, 29.2%) and infection (grade 3 to 4, 27.1%). CONCLUSIONS: Our results indicate that this regimen is a feasible treatment for elderly or poor performance status patients with unresectable NSCLC. Nevertheless, the morbidity due to myelosuppression and infection following this treatment should be carefully considered.

Endobronchial tuberculosis presenting as right middle lobe syndrome: clinical characteristics and bronchoscopic findings in 22 cases.

PURPOSE: Endobronchial tuberculosis (EBTB) presenting as right middle lobe syndrome (RMLS) is an uncommon clinical condition. We investigated the clinical characteristics in patients with EBTB presenting as RMLS. PATIENTS AND METHODS: We retrospectively reviewed the records of 22 patients with EBTB presenting as RMLS who were diagnosed at our hospital from 2003 to 2006. RESULTS: Its occurrence was more common in females than males (F, 18; M, 4). The mean age was 70.3 +/- 8.5 years, and 17 patients were above the age of 65 years. Cough with sputum was the most common manifestation and 2 patients were asymptomatic. In bronchoscopic analysis, the most common finding was edematous-type EBTB, which was found in 15 patients, followed by actively caseating type in 6 and tumorous type in 1. Acid-fast bacilli (AFB) staining for bronchial washing fluid was positive in only 5 patients: 1 with edematous type and 4 with actively caseating type. Bronchoscopic biopsy showed chronic granulomatous inflammation in 16 patients. Follow-up chest X-ray after treatment showed complete disappearance of the lesion in 2 patients, more than 50% improvement in 5, less than 50% improvement in 5, and no change of lesion in 4. CONCLUSION: Edematous-type EBTB was the most common type of EBTB presenting as RMLS, and it usually occurred in elderly patients. Culturing for mycobacterium and histologic examination by bronchoscopy are necessary for proper diagnosis in these patients.

Combination chemotherapy with irinotecan and cisplatin in elderly patients (>or= 65 years) with extensive-disease small-cell lung cancer.

INTRODUCTION: Combination chemotherapy with irinotecan and cisplatin is one of the standard treatments for patients with small-cell lung cancer (SCLC). In elderly patients, however, its efficacy and toxicity has not been well documented. In this Phase II study, we assessed the efficacy and toxicity of combination chemotherapy with irinotecan and cisplatin and examined whether advanced age compromises it in elderly patients with previously untreated extensive-disease small-cell lung cancer (ED-SCLC). METHODS: In this study, 46 previously untreated elderly patients (65 years or older) with ED-SCLC were given combination chemotherapy consisting of irinotecan 60 mg/m(2) on days 1, 8 and 15 and cisplatin 60 mg/m(2) on day 1. The treatment was repeated every 4 weeks until patients completed the maximum six cycles. RESULTS: Patients consisted of 37 men and 9 women, whose median age was 70 years (range 65-81 years). A complete response and a partial response were observed in 19.6% (9/46) and 56.5% (26/46), respectively. The overall response rate was 76.1% (95% C.I; 63.8-88.4%). The overall median survival was 10.4 months (range 7.6-13.2 months). The median progression-free survival was 8.32 months (range 6.8-9.8 months). Major toxicities included neutropenia (grade 3-4, 58.7%), leukopenia (grade 3-4, 49.9%), infection (grade 3-4, 39.1%) and diarrhea (grade 3-4, 30.4%). Incidence of febrile neutropenia was significantly higher in patients with ECOG performance status 2-3 compared with ECOG performance status 0-1 (70.4% vs. 5.2%; p<0.001). There were two treatment related deaths in patients ECOG performance status 3. CONCLUSIONS: Our results indicate that combination chemotherapy with irinotecan and cisplatin is an effective treatment for elderly patients with ED-SCLC who have good ECOG performance status and physicians should be aware of the mortality and morbidity due to myelosuppression following this treatment in elderly ED-SCLC patients with poor ECOG performance status.