Different characteristics associated with intensive care unit transfer from the medical ward between patients with acute exacerbations of chronic obstructive pulmonary disease with and without pneumonia.

BACKGROUND: The rate of hospitalization due to acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is increasing. Few studies have examined the clinical, laboratory and treatment differences between patients in general wards and those who need transfer to an intensive care unit (ICU). METHODS: We retrospectively reviewed clinical, laboratory, and treatment characteristics of 374 patients who were initially admitted to the general ward at Chonnam National University Hospital in South Korea due to AECOPD (pneumonic, 194; non-pneumonic, 180) between January 2008 and March 2015. Of these patients, 325 were managed at the medical ward during their hospitalization period (ward group), and 49 required ICU transfer (ICU group). We compared the clinical, laboratory, and treatment characteristics associated with ICU transfer between patients with AECOPD with and without pneumonia. RESULTS: Male patients were 86.5% in the ward group and 79.6% in the ICU group. High glucose levels [median 154.5 mg/dL, interquartile range (IQR) 126.8-218.3 in ICU group vs. median 133.0, IQR 109.8-160.3 in ward group], high pneumonia severity index scores (median 100.5, IQR 85.5-118.5 vs. median 86.0, IQR 75.0-103.5), low albumin levels (median 2.9 g/dL, IQR 2.6-3.6 vs. median 3.4, IQR 3.0-3.7), and anemia (73.3% vs. 43.3%) independently increased the risk of ICU transfer in the pneumonic AECOPD group. High PaCO2 levels (median 53.1 mmHg in ICU group, IQR 38.5-84.6 vs. median 39.7, IQR 34.2-48.6 in ward group) independently increased the risk of ICU transfer in the non-pneumonic AECOPD group. Treatment with systemic corticosteroids (≥30 mg of daily prednisolone) during hospitalization in the medical ward independently reduced the risk of ICU transfer in both groups. CONCLUSIONS: The characteristics associated with ICU transfer differed between the pneumonic and non-pneumonic AECOPD groups, and systemic corticosteroids use was associated with lower rate of ICU transfer in both groups.

Predictive factors for survival and correlation to toxicity in advanced Stage III non-small cell lung cancer patients with concurrent chemoradiation.

OBJECTIVE: Concurrent chemoradiotherapy is the standard treatment for locally advanced Stage III non-small cell lung cancer in patients with a good performance status and minimal weight loss. This study aimed to define subgroups with different survival outcomes and identify correlations with the radiation-related toxicities. METHODS: We retrospectively reviewed 381 locally advanced Stage III non-small cell lung cancer patients with a good performance status or weight loss of <10% who received concurrent chemoradiotherapy between 2004 and 2011. Three-dimensional conformal radiotherapy was administered once daily, combined with weekly chemotherapy. The Kaplan-Meier method was used for survival comparison and Cox regression for multivariate analysis. Multivariate analysis was performed using all variables with P values <0.1 from the univariate analysis. RESULTS: Median survival of all patients was 24 months. Age > 75 years, the diffusion lung capacity for carbon monoxide ≤80%, gross tumor volume ≥100 cm(3) and subcarinal nodal involvement were the statistically significant predictive factors for poor overall survival both in univariate and multivariate analyses. Patients were classified into four groups according to these four predictive factors. The median survival times were 36, 29, 18 and 14 months in Groups I, II, III and IV, respectively (P < 0.001). Rates of esophageal or lung toxicity ≥Grade 3 were 5.9, 14.1, 12.5 and 22.2%, respectively. The radiotherapy interruption rate differed significantly between the prognostic subgroups; 8.8, 15.4, 22.7 and 30.6%, respectively (P = 0.017). CONCLUSION: Severe toxicity and interruption of radiotherapy were more frequent in patients with multiple adverse predictive factors. To maintain the survival benefit in patients with concurrent chemoradiotherapy, strategies to reduce treatment-related toxicities need to be deeply considered.

Usefulness of Rigid Bronchoscopic Intervention Using Argon Plasma Coagulation for Central Airway Tumors.

OBJECTIVES: Argon plasma coagulation (APC) is a noncontact form of electrocautery that utilizes ionized argon as the electrical current. A rigid bronchoscopic use of APC for the management of central airway obstruction could be safe and rapidly effective. This study evaluated the usefulness of rigid bronchoscopy with APC for the management of central airway obstructions due to benign or malignant tumors. METHODS: Twenty patients with obstructing central airway tumors were retrospectively reviewed from February 2008 to February 2013 at Chonnam National University Hospital. All patients received rigid bronchoscopic tumor removal under general anesthesia. APC was applied before and after tumor removal. RESULTS: The median age of patients was 59 years (interquartile range [IQR], 51 to 67 years) and 70% were female. The causes of airway obstruction included malignancy (n=8) and benign tumor (n=12). Airway tumors comprised intraluminal lesions (n=11, 55%) and mixed intraluminal/extraluminal lesions (n=9, 45%). The median tumor size was 15 mm (IQR, 10 to 18 mm). The median degree of airway obstruction was significantly reduced after intervention (90% [IQR, 88% to 96%] vs. 10% [IQR, 0% to 20%], P<0.001). The median American Thoracic Society dyspnea grade (3 [IQR, 1 to 4] vs. 1 [IQR, 0 to 1], P<0.001) and forced expiratory volume in one second (1.03 L [IQR, 0.52 to 1.36 L] vs. 1.98 L [IQR, 1.57 to 2.64 L], P=0.004) were significantly improved after intervention. There were no procedure-related acute complications and deaths. CONCLUSION: Rigid bronchoscopy with APC is an effective and safe procedure to alleviate central airway obstruction caused by tumors.

Variability in the anti-tumor effect of tegafur-uracil depending on histologic types of lung cancer.

BACKGROUND: Tegafur-uracil (UFT) is an anticancer agent that inhibits thymidylate synthase (TS). The degree of TS expression in primary lung cancer (LC) is different according to histologic cell type. In this study, we examined the variability of the anti-tumor efficacy of UFT monotherapy depending on histological subtypes of LC. METHODS: In the current single-institution, retrospective study, we assigned the patients with LC to three histologic groups [the squamous (Sq) non-small cell lung cancer (NSCLC)] group, the non-Sq NSCLC group and the SCLC group] and then compared the clinical response to UFT monotherapy between the three groups. RESULTS: Our clinical series of 149 patients include 54 cases of Sq NSCLC, 67 cases of non-Sq NSCLC and 28 cases of SCLC. For Sq NSCLC, non-Sq NSCLC and SCLC group, the overall response rates (ORRs) were 1%, 1% and 0% (P=0.522), respectively. The disease control rates (DCRs) were 38.9%, 31.3% and 10.7% (P=0.012), respectively. The median progression-free survivals (PFSs) were 2.68, 2.25 and 1.46 months (P=0.004 for three groups and P=0.773 for two groups except for the SCLC group at the log-rank test), respectively. There was no significant difference between the groups in median overall survival (OS). CONCLUSIONS: Our results indicate that the degree of the anti-tumor effect of UFT was higher in patients with NSCLC as compared with SCLC. But it showed no significant difference between the patients with Sq NSCLC and those with non-Sq NSCLC.

Microarray analysis of gene expression in lung cancer cell lines treated by fractionated irradiation.

BACKGROUND: To identify differentially expressed genes between parent and radioresistant lung cancer cell lines established by fractionated irradiation. MATERIALS AND METHODS: Lung cancer cell lines (A549, NCI-H1650) were irradiated with several fractionation schemes. Clonogenic assays were used to identify radioresistant cell lines. We compared the gene expression profiles on a cDNA microarray. RESULTS: Four established cell (A549-2G, A549-5G, H1650-2G and H1650-5G) were shown to be radioresistant (p≤0.05). Seventy-two genes were commonly altered in A549-G and 655 genes in H1650-G, compared to their parental cells. Genes in the wingless-type MMTV integration site family (WNT) signaling pathway were the ones most frequently altered in both A549-G and H1650-G cells. Those involved in inflammation; integrin, platelet-derived growth factor (PDGF), interleukin, transforming growth factor-beta (TGFB), epidermal growth factor receptor (EGFR) signaling, were commonly altered in radioresistant H1650 sublines. CONCLUSION: The major gene expression changes during irradiation are related to WNT signaling pathway.

Prevalence of chronic sputum and associated factors in Korean adults.

Chronic sputum is a troublesome symptom in many respiratory diseases. The prevalence of chronic sputum varies from 1.2% to 13% according to the country. The purpose of this study was to estimate the prevalence of chronic sputum and to find its associated factors in a general Korean population. We analyzed the data of the Korea National Health and Nutrition Examination Survey 2010 and 2011. A total number of 6,783 subjects aged 40 yr or more were enrolled in this study with 3,002 men and 3,781 women. As a result, the prevalence of chronic sputum was 6.3% (n=430). Significant risk factors for chronic sputum by multivariate analysis were: age (≥ 70 yr) (odds ratio [OR], 1.954; 95% confidence interval [CI], 1.308-2.917), current smoking (OR, 4.496; 95% CI, 3.001-6.734), chronic obstructive pulmonary disease (COPD) (OR, 1.483; 95% CI, 1.090-2.018), and tuberculosis (OR, 1.959; 95% CI, 1.307-2.938). In conclusion, the prevalence of chronic sputum in Korea was in the intermediate range compared with other countries. Smoking is a preventable risk factor identified in this study, and major respiratory diseases, such as COPD and tuberculosis, should be considered in subjects with chronic sputum.

Early metabolic response on 18F-fluorodeoxyglucose-positron-emission tomography/computed tomography after concurrent chemoradiotherapy for advanced stage III non-small cell lung cancer is correlated with local tumor control and survival.

AIM: We evaluated the relationship of early metabolic responses on (18)F-fluorodeoxyglucose-positron-emission tomography/computed tomography (PET/CT) performed within one month after concurrent chemoradiotherapy (CCRT) with local tumor control and survival in patients with advanced stage III non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: One hundred and nineteen patients with unresectable stage III NSCLC who completed definitive CCRT were included. PET/CT was performed 2-4 weeks after completion of radiotherapy. RESULTS: The maximum standardized uptake value (SUVmax) reduction ratio of the primary lesion (primary SRR, 80%, p<0.001), gross tumor volume (150 cm(3), p=0.036), and pre-radiotherapy ratio of SUVmax of the metastatic lymph node to that of the primary lesion (60%, p=0.05) were significantly associated with OS in multivariate analysis. The primary SRR was the only statistically significant parameter for local control. CONCLUSION: Early metabolic response of the primary lesion after CCRT correlated with local control and overall survival in patients with unresectable stage III NSCLC.

A phase III concurrent chemoradiotherapy trial with cisplatin and paclitaxel or docetaxel or gemcitabine in unresectable non-small cell lung cancer: KASLC 0401.

PURPOSE: Concurrent chemoradiotherapy (CCRT) is recommended for the management of patients with unresectable non-small cell lung cancer (NSCLC). This prospective study aimed to compare the efficacy of concurrently delivered cisplatin doublets with paclitaxel, or docetaxel, or gemcitabine. METHODS: The main eligibility criteria consisted of previously untreated stage IIIB NSCLC. The subjects were randomized into three arms: paclitaxel 45 mg/m(2)/week (TP), docetaxel 20 mg/m(2)/week (DP), and gemcitabine 350 mg/m(2)/week (GP) in addition to cisplatin 20 mg/m(2)/week. Three-dimensional conformal radiotherapy was given once daily, weekly 5 fractions and the total prescription dose was 60-66 Gy. The primary endpoint was response rate, and the secondary endpoints were survival and toxicity. RESULTS: A total of 101 patients were recruited into this trial of whom 93 (TP: 33, DP: 29, GP: 31) patients were treated with CCRT from March 2005 to July 2007. Similar response rates were observed across arms: TP: 63.6 %, DP: 72.4 %, GP: 61.3 % (p = 0.679). There was no statistically significant difference of median survival (TP: 27.3, DP: 27.6, GP: 16.5 months, p = 0.771). In subgroup analysis, a survival benefit of consolidation chemotherapy was not seen, but leucopenia (63.2 %) and neutropenia (68.4 %) more than grade 3 were significantly high in DP arm. The grade ≥3 radiation esophagitis was more frequent in the GP arm (22.6 %, p = 0.163). CONCLUSIONS: Among the three arms, no statistically significant difference in response rate, survival, and toxicity was observed. However, clinically significant radiation toxicity was more frequent in the GP arm.

Differences in classification of COPD group using COPD assessment test (CAT) or modified Medical Research Council (mMRC) dyspnea scores: a cross-sectional analyses.

BACKGROUND: The GOLD 2011 document proposed a new classification system for COPD combining symptom assessment by COPD assessment test (CAT) or modified Medical Research Council (mMRC) dyspnea scores, and exacerbation risk. We postulated that classification of COPD would be different by the symptom scale; CAT vs mMRC. METHODS: Outpatients with COPD were enrolled from January to June in 2012. The patients were categorized into A, B, C, and D according to the GOLD 2011; patients were categorized twice with mMRC and CAT score for symptom assessment, respectively. Additionally, correlations between mMRC scores and each item of CAT scores were analyzed. RESULTS: Classification of 257 patients using the CAT score vs mMRC scale was as follows. By using CAT score, 60 (23.3%) patients were assigned to group A, 55 (21.4%) to group B, 21 (8.2%) to group C, and 121 (47.1%) to group D. On the basis of the mMRC scale, 97 (37.7%) patients were assigned to group A, 18 (7.0%) to group B, 62 (24.1%) to group C, and 80 (31.1%) to group D. The kappa of agreement for the GOLD groups classified by CAT and mMRC was 0.510. The mMRC score displayed a wide range of correlation with each CAT item (r = 0.290 for sputum item to r = 0.731 for dyspnea item, p < 0.001). CONCLUSIONS: The classification of COPD produced by the mMRC or CAT score was not identical. Care should be taken when stratifying COPD patients with one symptom scale versus another according to the GOLD 2011 document.

Endotracheal tuberculous granuloma formation following endobronchial ultrasound transbronchial needle aspiration.

Endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) is a useful and safe diagnostic test. We herein report a case of endotracheal granuloma formation that occurred after EBUS-TBNA in a 73-year-old woman. The patient was admitted due to coughing and dyspnea after 70 days of antituberculous therapy for mediastinal lymphadenitis. Computed tomography revealed decreases in the size of the lymph nodes with a new mass protruding into the tracheal lumen. The mass originated from the right paratracheal area, which was a previous puncture site. This case suggests that clinicians should pay attention to complications because tuberculosis can produce new granulomas via the sinus tract after EBUS-TBNA.

Repeated favorable responses to epidermal growth factor receptor-tyrosine kinase inhibitors in a case of advanced lung adenocarcinoma.

The presence of epidermal growth factor receptor (EGFR) mutation is a prognostic and predictive marker for EGFR-tyrosine kinase inhibitor (TKI) therapy. However, inevitably, relapse occurs due to the development of acquired resistance, such as T790M mutation. We report a case of repeated responses to EGFR-TKIs in a never-smoked woman with adenocarcinoma. After six cycles of gemcitabine and cisplatin, the patient was treated by gefitinib for 4 months until progression. Following the six cycles of third-line pemetrexed, gefitinib retreatment was initiated and continued with a partial response for 6 months. After progression, she was recruited for an irreversible EGFR inhibitor trial, and the time to progression was 11 months. Although EGFR direct sequencing on the initial diagnostic specimen revealed a wild-type, we performed a rebiopsy from the progressed subcarinal node at the end of the trial. The result of peptide nucleic acid clamping showed L858R/L861Q.

Analysis of patients with hemoptysis in a tertiary referral hospital.

BACKGROUND: This study attempted to investigate the main causes of hemoptysis, the type of examinations used for diagnosis, the treatment modalities and outcomes. METHODS: A retrospective study was conducted on the medical records of 221 patients admitted to the Chonnam National University Hospital, between January 2005 and February 2010, with hemoptysis. RESULTS: Bronchiectasis (32.6%), active pulmonary tuberculosis (18.5%), fungus ball (10.8%), and lung cancer (5.9%) accounted for most causes of hemoptysis. Computed tomography scan was the most sensitive diagnostic test when employed alone, with positive yield of 93.2%. There were 161 cases of conservative treatment (72.9%), 42 cases of bronchial artery embolization (BAE) (19.0%), and 18 cases of surgery (8.1%). Regarding the amount of hemoptysis, 70 cases, out of 221 cases, were mild (31.5%), 36 cases moderate (16.2%), and 115 cases massive hemoptysis (52.0%). Most of the patients were treated conservatively, but if there was more bleeding present, BAE or surgery was more commonly performed than the conservative treatment (p≤0.0001). In the multivariate model, severe hemoptysis and lung cancer were independently associated with short-term recurrence. BAE was independently associated with long-term recurrence, and lung cancer was associated with in-hospital mortality. The overall in-hospital mortality rate was 11.3%. CONCLUSION: Hemoptysis is a common symptom with a good prognosis in most cases. However, patients exhibiting massive bleeding or those with malignancy had a poorer prognosis. In-hospital mortality was strongly related to the cause, especially in lung cancer.

Comparison of docetaxel/cisplatin dosages of 75/60 and 60/60 mg/m(2) for the treatment of non-small cell lung cancer.

A combination of docetaxel (D) and cisplatin (P) is one of the standard regimens for the initial treatment of advanced non-small cell lung cancer (NSCLC). Yet, the toxicity of D administered at 75 mg/m(2) in three weekly doses to patients is a concern. The aim of this study was to assess the efficacy of a lower combination dose, 60 mg/m(2) of D and 60 mg/m(2) of cisplatin (P), as a treatment for NSCLC. In this randomized, phase III trial, we compared the response rates (RRs) and toxicity profiles of two combination regimens, D/P 75/60 vs. 60/60 mg/m(2), to patients with stage IIIB or IV NSCLC. A total of 132 patients were randomized to the 75/60 (n=65) or 60/60 (n=67) dosage group. Non-inferiority of 60/60 group compared to the 75/60 group was confirmed by the RR (38.5% for the 75/60 group and 40.3% for the 60/60 group, 95% confidence interval -14.8 to 18.5, meeting the predefined non-inferiority criterion). The dose reduction rate and incidence of grade 3-4 neutropenia were significantly higher in the 75/60 group. The incidence of neutropenia was significantly higher in those with the non-expressing genotype (GG) compared to the AG or AA genotypes of CYP3A5. We determined that DP 60/60 was not inferior to DP 75/60 in RR, and that the reduced combination dosage provides a better safety profile for patients.

Temozolomide-associated bronchiolitis obliterans organizing pneumonia successfully treated with high-dose corticosteroid.

Temozolomide is an oral alkylating agent with clinical activity against glioblastoma multiforme (GM). It is generally well-tolerated and has few pulmonary side effects. We report a case of temozolomide-associated brochiolitis obliterans organizing pneumonia (BOOP) requiring very high-dose corticosteroid treatment. A 56-yr-old woman presented with a 2-week history of exertional dyspnea. For the treatment of GM diagnosed 4 months previously, she had undergone surgery followed by chemoradiotherapy, and then planned adjuvant chemotherapy with temozolomide. After the 1st cycle, progressive dyspnea was gradually developed. Chest radiograph showed diffuse patchy peribronchovascular ground-glass opacities in both lungs. Conventional dose of methylprednisolone (1 mg/kg/day) was begun for the possibility of BOOP. Although transbronchial lung biopsy findings were compatible with BOOP, the patient's clinical course was more aggravated until hospital day 5. After the dose of methylprednisolone was increased (500 mg/day for 5 days) radiologic findings were improved dramatically.

Retreatment of gefitinib in patients with non-small-cell lung cancer who previously controlled to gefitinib: a single-arm, open-label, phase II study.

Most patients with non-small-cell lung cancer (NSCLC) who initially respond to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) eventually experience progression of disease. Based on previous trials which showed second response after switching to another EGFR-TKI, we hypothesized that the reintroduction of gefitinib would lead to disease control rate (DCR) in more than 30% of patients. This was a single-arm, open-label, prospective, phase II trial of gefitinib for the treatment of advanced or metastatic NSCLC. Eligible patients had previously responded to, or had experienced disease stabilization with, initial gefitinib treatment for at least 3 months. Prior to retreatment, progressive disease (PD) should be observed, with at least one cytotoxic treatment following initial gefitinib failure. Twenty-three patients were recruited and defined as the intention to treat (ITT) group. Most of the enrolled patients were female (86.9%), never-smokers (91.3%), and adenocarcinoma patients (95.7%). Responses to initial gefitinib were partial response (PR) in 10 cases (43.5%) and stable disease (SD) in 13 cases (56.5%). PR and DCR were observed in 21.7% (5 patients) and 65.2% (15 patients) in the ITT group. Among 14 DNA samples, 13 cases had either exon 19 deletion or L858R point mutation, whereas one patient evidenced the wild-type EGFR gene. Re-initiation of EGFR-TKI can be considered as an option after failure of chemotherapy for those patients who previously controlled to EGFR-TKI treatment.

Plasma N-terminal pro-brain natriuretic peptide: a prognostic marker in patients with chronic obstructive pulmonary disease.

BACKGROUND: Plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) levels are elevated in patients with secondary pulmonary hypertension and chronic lung disease with right ventricular overload. The aim of the present study was to investigate the use of plasma NT-proBNP levels as a prognostic marker of severe COPD with chronic respiratory failure and latent pulmonary hypertension. METHODS: Plasma NT-proBNP levels were measured in 61 patients with stable COPD. Plasma NT-proBNP levels, pulmonary function, PaO(2), and PaCO(2) levels and systolic pulmonary artery pressure were compared according to COPD severity. In addition, we examined correlations between plasma NT-proBNP levels and pulmonary function, PaO(2), PaCO(2), and systolic pulmonary artery pressure. RESULTS: The levels of plasma NT-proBNP significantly increased in patients with stage IV and stage III COPD compared to individuals with stage II COPD according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification. The area under the receiver-operating characteristic curve of plasma NT-proBNP for severe to very severe COPD (FEV(1) <50%) was 0.707 (95% confidence interval [CI] 0.566-0.847, P=0.008). Plasma NT-proBNP levels significantly correlated with %FEV(1) (r= -0.557; P < 0.001), arterial blood gas parameters such as PaCO(2) (r = 0.476; P < 0.001) and PaO(2) (r = -0.347; P = 0.031), and systolic pulmonary artery pressure (r = 0.435; P = 0.001). CONCLUSIONS: Plasma NT-proBNP levels increased significantly with disease severity, progression of chronic respiratory failure, and secondary pulmonary hypertension in patients with stable COPD. These results suggest that plasma NT-proBNP can be a useful prognostic marker to monitor COPD progression and identify cases of secondary pulmonary hypertension in patients with stable COPD.

Invariant natural killer T cells in chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVE: Invariant natural killer T (iNKT) cells may play an important role in regulating the innate and acquired immune systems in chronic obstructive pulmonary disease (COPD). However, there is little information regarding the potential role of iNKT cells in the pathogenesis of COPD. To investigate whether iNKT cells have an important role in COPD, the frequency of iNKT cells in peripheral blood of patients with COPD was analysed. METHODS: This was a comparative study of 28 patients with COPD and 19 age-matched healthy control subjects. Blood iNKT cells were stained with 6B11 mAb, anti-T cell receptor Vα24 mAb, anti-T cell receptor Vß11 mAb or α-galactosylceramide-loaded CD1d-tetramer, and analysed by flow cytometry. RESULTS: The frequency of CD4(+) 6B11(+) iNKT, CD4(+) Vα24(+) iNKT, CD4(+) Vß11(+) iNKT and CD3(+) 6B11(+) iNKT cells was significantly lower in peripheral blood of patients with COPD than in that of healthy control subjects. The frequency of CD4(+) 6B11(+) iNKT cells was significantly lower in patients with exacerbations of COPD compared with those with stable COPD. CONCLUSIONS: The frequency of iNKT was decreased in peripheral blood of patients with COPD. These results strongly suggest that iNKT cells may play an important role in the pathogenesis of COPD.

Disease-free survival of patients after surgical resection of non-small cell lung carcinoma and correlation with excision repair cross-complementation group 1 expression and genotype.

BACKGROUND AND OBJECTIVE: Expression of excision repair cross-complementation group 1 (ERCC1) is recognized as a favourable prognostic marker in patients who have undergone surgical resection of non-small cell lung cancer (NSCLC). However, in patients treated with adjuvant chemotherapy after surgical resection, ERCC1 correlated with poor prognosis. Class III beta tubulin (TUBB3) is also known to be a predictive marker of the efficacy of treatment with taxanes or vinorelbine. METHODS: Tumour tissues (n = 363) from patients with surgically resected NSCLC were analysed retrospectively. Tissue sections were labelled with ERCC1- and TUBB3-specific antibodies. Using genomic DNA from 262 patients, single nucleotide polymorphisms of the ERCC1 gene (T19007C and C8092A) were genotyped by PCR-restriction fragment length polymorphism analysis. RESULTS: Only 5.9% of patients with stage I disease (14/238) and 61.6% of patients with stages II-III disease (77/125) received adjuvant chemotherapy. Relapses were noted in 30.6% (111) of patients, and among these, 31 ultimately succumbed. The relapse rate (RR) was 24.8% for stage I disease, and 41.6% for stages II-III disease. The RR was significantly lower in ERCC1-positive (24.3%) as compared with ERCC1-negative patients (36.3%, P = 0.014) and was lower in patients with the AA/CA genotype at the ERCC1 C8092A locus (29.5%) compared with those with the CC genotype (42.1%, P = 0.034). The median disease-free survival (DFS) time was 62.3 months. DFS was significantly greater in ERCC1-positive patients (62.3 months) than in ERCC1-negative patients (48.0 months, P = 0.042). In a multivariate analysis, ERCC1 expression and the C8092A polymorphism were independent prognostic factors in patients with stage I disease who were naïve to chemotherapy. CONCLUSIONS: ERCC1 expression and the AA/CA genotype at the C8092A locus were correlated with a good prognosis in patients who had undergone surgical resection of NSCLC.

Response to gemcitabine-platinum chemotherapy by single nucleotide polymorphisms of RRM1 and ERCC1 genes in patients with non-small-cell lung cancer.

BACKGROUND: RRM1, the regulatory subunit of ribonucleotide reductase, is involved in carcinogenesis and the response to gemcitabine. Two single nucleotide polymorphisms (SNP) in the RRM1 gene (RR37 and RR524) impact promoter activity and are associated with prognosis. The excision repair cross-complementation group 1 protein (ERCC1) is associated with platinum resistance. A SNP of the ERCC1 gene (T19007C) has been reported as a prognostic marker in platinum-treated non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: Patients with stage IIIB or IV NSCLC were treated with gemcitabine and platinum (GP) as first-line chemotherapy. Adenocarcinoma was the most frequent histological type, followed by squamous cell carcinoma and then other types. SNP were analyzed with real time-polymerase chain reaction using genomic DNA extracted from peripheral blood. RESULTS: Based on responses to GP patients were classified as responders or non-responders. The response rate was significantly higher in patients with the RR AC-CT genotype (35/64, 54.7%) compared to those with the RR CC-TT genotype (56/147, 38.1%, P= 0.025). No significant difference in response rate was observed according to ERCC1 genotype. In 128 patients with non-squamous cell lung cancer, RR AC-CT + ERCC1 CC (63.2%) and RR AC-CT + ERCC1 CT/TT (61.9%) showed higher response rates compared to RR CC-TT + ERCC1 CC (36.5%), and RR CC-TT + ERCC1 CT/TT (22.2%; P= 0.004). Progression-free and overall survival times were not different between genotypes. CONCLUSIONS: We observed significantly different responses to the GP regimen according to SNP of the RRM1 and ERCC1 genes.

Proportion and characteristics of transient nodules in a retrospective analysis of pulmonary nodules.

BACKGROUND: Pulmonary nodules manifest as pure or mixed ground glass opacities (GGOs), or solid nodules. METHODS: We retrospectively surveyed 317 cases with pulmonary nodules to observe the proportion and predictive factors of transient lesions in patients with pulmonary nodules. RESULTS: At the initial computed tomography scan, 63.7% showed solid nodules, while 20.2% had mixed GGOs and 16.1% of cases manifested as pure GGOs. Nodules from 114 cases (36%) disappeared or decreased in size during follow up, while in 203 cases (64%), they did not change or became enlarged. During follow up, more than half of the GGOs resolved (66.7% in pure GGOs, 54.7% in mixed GGOs), while only 22.3% of solid nodules resolved. Between transient and persistent pulmonary nodules, significant differences were observed in age, gender, smoking history, presence of eosinophilia, size, and radiologic attenuation of nodules (solid or GGO). In multivariate analysis, age (≤55 years), size of nodules (>15 mm), eosinophilia, and GGO were significant independent predictors of transient nodules. The main causes of transient nodules were pneumonia or eosinophilic pulmonary infiltrates. CONCLUSION: Thirty-six percent of pulmonary nodules resolved spontaneously or with medical treatment. Transient nodules showed different clinical and radiological characteristics from persistent nodules.