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Background: The immunological features of eosinophils in early-onset asthma (EOA) differs from that in late-onset asthma (LOA). Clinical trials of anti-interleukin-5 (IL-5) treatment for severe eosinophilic asthma showed a better response for LOA patients than EOA patients. We wonder if the transcriptional activity of activated eosinophils was different in EOA and LOA. Methods: Eosinophils obtained from well controlled EOA and LOA patients and normal subjects were compared in terms of the mRNA expression of activation-related genes (integrins α4 and β2, CCR3, CCR5, and IL-5Rα, and IL-17RA) and specific markers (IL-4Rα, prostaglandin D2 receptor 2, high-affinity IgE receptor, TGF-β1, aryl hydrocarbon receptor, and endosomal TLR-3, 7, and 9) in eosinophils activated by IL-5 or IL-17. The correlation between mRNA expression and clinical features and lung function were further analyzed. Results: The transcriptional expression of most genes was higher in activated eosinophils from LOA patients than in those from EOA patients and normal subjects. After IL-17 stimulation, the expression of certain genes was higher in atopic EOA patients than in non-atopic EOA patients. Similar observation was noted in obese EOA patients. After IL-5 stimulation, the transcriptional expression of most genes in eosinophils from LOA patients was negatively correlated with indicators of lung function. These correlations were less pronounced in EOA patients: After IL-17 stimulation, some genes in EOA patients were negatively correlated with post-bronchodilator changes in lung function. There was no significant correlation between mRNA expression and treatment control levels among LOA or EOA patients Conclusion: This study describes differences in the transcriptional active patterns of eosinophils and their correlation to atopy and obese by age of onset. High transcriptional activity in activated eosinophils and a negative correlation to lung function indicate the importance of eosinophils in the pathogenesis of LOA.

The circulating progenitor cells of fibroblasts (fibrocytes) have been shown to infiltrate the airway smooth muscle compartment of asthma patients; however, the pathological significance of this discovery has yet to be elucidated. This study established a co-culture model of airway smooth muscle cells (ASMCs) and fibrocytes from asthmatic or normal subjects to evaluate innate cytokine production, corticosteroid responses, and signaling in ASMCs.CD34Compared with ASMCs cultured alone, IL-8 levels in the supernatant and IL-33 levels in the ASMCs lysate were significantly higher in samples co-cultured from asthmatics, but not in those co-cultured from normal subjects. Corticosteroid-induced suppression of IL-8 production was less pronounced in ASMCs co-cultured with fibrocytes from asthma patients than in ASMCs co-cultured from normal subjects. ASMCs stimulated using PtCM and IL-8 presented elevating activated AKT substrate PRAS40. Treatment with IL-8 and PtCM increased mRNA expression of mTOR and P70S6 kinases in ASMCs. Treatment with IL-8 and PtCM also significantly increased phosphorylation of AKT and mTOR subtract S6 ribosomal protein in ASMCs.The interaction between ASMCs and fibrocytes from asthmatic patients was shown to increase IL-8 and IL-33 production and promote AKT/mTOR signaling in ASMCs. IL-8 production in the co-culture from asthmatic patients was less affected by corticosteroid than was that in the co-culture from normal subjects. Our results elucidate the novel role of fibrocytes and ASMCs in the pathogenesis of asthma.

This study aims to investigate postdonation outcomes of adult living donor liver transplantation donors and remnant liver regeneration in different graft types.A total of 236 adult living donor liver transplantation donors were classified into different groups: donors with 35% remnant liver volume (group A; n = 56) and donors with remnant liver volume ≥35% (group B, n = 180); left lobe grafts (LLG group; n = 98) including middle hepatic vein (MHV) and right lobe grafts (RLG group; n = 138) without MHV. The 98 LLG group donors were further classified into 2 subgroups based on hepatic venous drainage patterns: MHV-dominant (n = 20) and non-MHV-dominant (n = 78). The demographic data, postoperative laboratory data, complications, graft weight, remnant liver volume, remnant liver growth rate, and remnant liver regeneration rate (RLRR) after partial liver donation were analyzed.The postoperative aspartate aminotransferase, alanine aminotransferase, total bilirubin, intensive care unit stays, and hospitalization stays were higher in A and RLG group donors. All the donor complications in our series were minor complications. The postoperative complication rate was higher in the A and RLG group, but failed to reach statistical significance. There was no significant difference in RLRR between the RLG/LLG and A/B groups. However, the MHV-dominant group had significantly lower RLRR than the non-MHV-dominant group (P .05).Small remnant liver volume donors (35% remnant liver) have higher risks of developing postdonation minor complications. Left lobe liver donation in MHV-dominant donor candidates are a major concern.

// Po-Hao Feng 1, 2 , Chih-Teng Yu 3 , Kuan-Yuan Chen 1, 4 , Ching-Shan Luo 1 , Shen Ming Wu 1 , Chien-Ying Liu 3 , Lu Wei Kuo 1 , Yao-Fei Chan 3 , Tzu-Tao Chen 1 , Chih-Cheng Chang 1 , Chun-Nin Lee 1 , Hsiao-Chi Chuang 5 , Chiou-Feng Lin 6 , Chia-Li Han 7 , Wei-Hwa Lee 8 and Kang-Yun Lee 1, 2 1 Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan 2 Division of Thoracic Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan 3 Division of Pulmonary Medicine, Department of Internal Medicine, Chang Gung Medical Foundation Linko Branch, Taoyuan, Taiwan 4 Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan 5 School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan 6 Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan 7 Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, College of Pharmacy, Taipei Medical University, Taipei, Taiwan 8 Department of Pathology, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan Correspondence to: Kang-Yun Lee, email: lee4949@ms41.hinet.net Keywords: lung cancer; myeloid derived suppressor cells; epidermal growth factor receptor; macrophages; NF-kappa B Received: September 06, 2017 Accepted: January 03, 2018 Published: January 10, 2018 ABSTRACT Background: Monocytic myeloid-derived suppressor cells (MDSCs), particularly the S100A9+ subset, has been shown initial clinical relevance. However, its role in EGFR-mutated lung adenocarcinoma, especially to EGFR-tyrosine kinase inhibitor (EGFR-TKI) is not clear. In a clinical setting of EGFR mutated lung adenocarcinoma, a role of the MDSC apart from T cell suppression was also investigated. Results: Blood monocytic S100A9 + MDSC counts were higher in lung cancer patients than healthy donors, and were associated with poor treatment response and shorter progression-free survival (PFS). S100A9 + MDSCs in PBMC were well correlated to tumor infiltrating CD68 + and S100A9 + cells, suggesting an origin of TAMs. Patient’s MDMs, mostly from S100A9 + MDSC, similar to primary alveolar macrophages from patients, both expressed S100A9 and CD206, attenuated EGFR-TKI cytotoxicity. Microarray analysis identified up-regulation of the RELB signaling genes, confirmed by Western blotting and functionally by RELB knockdown. Conclusions: In conclusion, blood S100A9 + MDSC is a predictor of poor treatment response to EGFR-TKI, possibly via its derived TAMs through activation of the non-canonical NF-κB RELB pathway. Methods: Patients with activating EGFR mutation lung adenocarcinoma receiving first line EGFR TKIs were prospectively enrolled. Peripheral blood mononuclear cells (PBMCs) were collected for MDSCs analysis and for monocyte-derived macrophages (MDMs) and stored tissue for TAM analysis by IHC. A transwell co-culture system of MDMs/macrophages and H827 cells was used to detect the effect of macrophages on H827 and microarray analysis to explore the underlying molecular mechanisms, functionally confirmed by RNA interference.

// Chien-Ying Liu 1, 2 , Chih-Liang Wang 1, 2 , Shih-Hong Li 1 , Ping-Chih Hsu 1 , Chih-Hung Chen 1 , Ting-Yu Lin 1, 2 , Chih-Hsi Kuo 1, 2 , Yueh-Fu Fang 1, 2 , How-Wen Ko 1 , Chih-Teng Yu 1, 2 , Tai-Yun Yang 1, 2 and Cheng-Ta Yang 1, 2 1 Division of Pulmonary Oncology, Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan 2 School of Medicine, Chang Gung University, Taoyuan, Taiwan Correspondence to: Cheng-Ta Yang, email: yang1946@cgmh.org.tw Keywords: afatinib, dose de-escalation, epidermal growth factor mutations, lung adenocarcinoma, therapeutic efficacy Received: January 12, 2017 Accepted: March 22, 2017 Published: June 27, 2017 ABSTRACT The choice of a first-line therapy for lung cancer is a crucial decision that can impact the survival as well as the quality of life of a patient. Inhibitors of epidermal growth factor receptor (EGFR) such as afatinib, erlotinib, and gefitinib have previously been used to treat non-small cell lung cancer harboring favorable EGFR mutations. Although afatinib has greater efficacy than other EGFR inhibitors, adverse events related to its use can result in the discontinuation of the therapy. In this study, we compared the therapeutic efficacy in lung cancer patients of a regimen of 40 mg/day of afatinib with that of a lower dose regimen of

Background The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) eventually fails in treating advanced lung adenocarcinoma harboring sensitive EGFR mutations because of acquired resistance. In clinical practical setting, platinum-doublet chemotherapy has been frequently performed after failure of first-line EGFR-TKIs. The efficacy of different regimens was compared. Methods From January 2012 to December 2013, 160 patients with mutated EGFR receiving first-line EGFR-TKIs and second-line chemotherapy were analyzed retrospectively. Sixty-eight patients received pemetrexed-based therapy and among them, 61 were in combination with cisplatin. Ninety-two patients received non-pemetrexed-based therapy and among them, 79 were combined with cisplatin. Results The progression-free survival of first-line EGFR-KI was 9.0 and 8.6 months for pemetrexed and non-pemetrexed treatment groups respectively (HR: 0.9146, 95% CI: 0.6656 to 1.257, P =0.5818). The median progression-free survival (PFS) of second-line therapy was 8.3 and 5.6 months for pemetrexed and non-pemetrexed treatment groups respectively (HR: 0.4217, 95% CI: 0.2952 to 0.6025, P =0.0001). The median overall survival (OS) after first-line EGFR-TKIs was 16.9 and 10.3 months for pemetrexed and non-pemetrexed groups respectively (HR: 0.5160, 95% CI: 0.3381 to 0.7873, P =0.0021). For those receiving pemetrexed continuous maintenance therapy, there was 18.7 months of survival after first-line EGFR-TKI, compared to 11.1 months for those without maintenance (HR: 0.4012, 95% CI: 0.2577 to 0.6247, P Conclusion The efficacy of pemetrexed was superior to other chemotherapeutic agents in second line treatment for patients with lung adenocarcinoma harboring sensitive EGFR mutations after first-line EGFR-TKI therapy. Continuous maintenance pemetrexed therapy also improved the PFS and OS.

Objective Optimal hepatic venous tributary flow is correlated with liver function and regeneration. In left-lobe graft living donor liver transplantation, the stump of segment 5 and 8 hepatic veins (S5V and S8V) are ligated without performing hepatic tributary reconstruction. The aim of this article was to evaluate the different dominate hepatic vein patterns that affect left-lobe living donor safety. Materials and Methods A total of 44 donors who underwent left-lobe hepatectomy were divided into 2 groups, middle hepatic vein (MHV) dominance (group 1) and right hepatic vein (RHV) dominance (group 2), according to the dominant venous territory drainage from S5V and S8V or RHV. The clinical pathological data, postoperative laboratory data, complication, remnant liver volume and remnant liver regeneration rate at 6 months after surgery were compared. Results No difference was found in blood loss, postoperative liver function such as alanine transaminase value, complications, and hospital stays between groups. Group 1 had slightly higher total bilirubin level than group 2 (1.99 vs 1.79; P = .49). Group 2 had significantly better remnant liver regeneration rate than group 1 (89.2% vs 82.5%; P = .026). Conclusion It is important to recognize the dominant MHV group. Ligation large S5V and S8V in dominant MHV donors led to lower remnant liver regeneration in our series. This might be critical in extremely small RHV territory and potential large remnant liver congestion donors. Adjusting surgical planning, such as hepatic vein reconstruction, in this kind of donor might be appropriate for donor safety.

Liver regeneration and donor safety in right-lobe (RL) and left-lobe (LL) grafts are essential for donors in living donor liver transplantation (LDLT). Our aim was to compare the liver regeneration rate and postoperative outcome between different donor graft types in LDLT.A total of 95 donors were divided into 2 groups: RL (n = 42) and LL (n = 53). The remnant liver of LL donors were subdivided into 3 subgroups according to the different hepatic venous drainage pattern that dominates from right hepatic vein (dominant RHV; n = 34), middle hepatic vein (dominant MHV; n = 10), and include MHV for left lateral segment (LLS) graft (n = 9). The demographic data, postoperative laboratory data, complications, remnant liver volume (RLV), and remnant liver regeneration rate (RLRR) 6 months after surgery were compared.The postoperative total bilirubin (TB), prothrombin time (PT), and intensive care unit (ICU) stays of the LL group were lower than the RL group (P .05). The LL group has no significant better regeneration rate 6 months after surgery than the RL group. However, dominant RHV and LLS groups have significantly better RLRR than the RL group (89.2% vs 86% and 95.1% vs 86%, respectively, P .05), but no significance in the dominant MHV group.In conclusion, different hepatic venous drainage patterns of remnant liver grafts may affect the regeneration rate in LL LDLT, especially with dominant RHV donors, may have more comparable outcomes with that of RL, and should be a favorable option during donor selection.

The study aim was to compare the long-term effect of Western medicine and combined treatment with Traditional Chinese Medicine (TCM) and Western medicine on the prognosis (survival rate, symptom distress, physical function, and quality of life) of patients with lung cancer.Longitudinal study.Two medical centers, one each in Northern and Southern Taiwan.Patients newly diagnosed with lung cancer and treated with Western medicine (n = 54) or TCM plus Western medicine (n = 30).Symptom distress, physical function, and quality of life were measured by using the Symptom Distress Scale, Eastern Cooperative Oncology Group-Performance Status Rating, and European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ-C30 and EORTC QLQ-LC13), respectively. Data on these measures were collected at baseline (before treatment) and 1, 3, 6, and 12 months after starting treatment. Survival was estimated by Kaplan-Meier curves. Group differences in outcomes were analyzed by generalized estimating equations.Treatment groups did not differ significantly at baseline for demographic information; disease severity; symptom distress; or EORTC QLQ-C30 and QLQ-LC13 scores, except for pain and dyspnea. After adjustment for these baseline effects, the combined-treatment group had better physical function and role function than the Western medicine group at 6 months (p 0.05). The combined treatment group had better cumulative survival, but this difference did not reach significance.To more precisely estimate the long-term effectiveness of combined treatment on the prognosis of patients with lung cancer, future studies should standardize the number of TCM visits; increase the number of participants by continuous recruitment; and ask patients to complete daily logs with single-item measures of outcomes, such as symptom distress, quality of life, and physical function. Similar studies are suggested in patients with different cancers to develop a collaborative model using Western medicine and TCM.

Summary Background This study explored the effects of acupressure on fatigue of lung cancer patients undergoing chemotherapy. Patients and methods For this experimental study, 57 subjects were randomly assigned to three groups: acupressure with essential oils ( n =17), acupressure only ( n =24), and sham acupressure ( n =16). Acupoints were Hegu (LI4), Zusanli (ST36), and Sanyingjiao (SP6). All subjects received acupressure once every morning for 5 months, with each acupoint pressed for 1min. Fatigue, functional status, anxiety, depression, and sleep quality were measured before initial chemotherapy (T0), on Day 1 of third chemotherapy (T1), and on Day 1 of sixth chemotherapy (T2). Outcome differences between groups were analyzed at T0, T1, and T2 by general estimating equations. Results After controlling for baseline outcome values, age, and adherence to acupressure, subjects who received acupressure with essential oils and acupressure had significantly less fatigue in daily living activities and sleep better quality at T1 than subjects who received sham acupressure. Subjects who received acupressure with essential oils had significantly better sleep quality at T2 than the sham acupressure group. Subjects who received acupressure with or without essential oils had greater odds of better functional status at T1 than the sham group. Conclusion It is plausible that acupressure with or without essential oils helps lung cancer patients undergoing chemotherapy reduce cancer-related fatigue and increase activity level. Further study is wanted to test this hypothesis.

OBJECTIVES To systematically and quantitatively summarise the current evidence on the utility of the procalcitonin test (PCT) in discriminating pulmonary tuberculosis (TB) from other pulmonary infections. METHODS We searched MEDLINE, EMBASE and the Cochrane database up to August 2013 for studies that reported the performance of PCT alone or compared with other biomarkers in diagnosing pulmonary TB. We summarised PCT using forest plots, hierarchical summary receiver operating characteristic curves and bivariate random effects models. RESULTS We found nine qualifying studies covering 951 episodes of suspected TB along with 426 confirmed TB cases. The bivariate pooled sensitivity and specificity of PCT to distinguish TB from non-TB were respectively 42% (95%CI 30-56) and 87% (95%CI 63-96). The bivariate pooled sensitivity and specificity for PCT in distinguishing TB from bacterial pneumonia were respectively 78% (95%CI 67-86) and 85% (95%CI 78-90). Low heterogeneity was noted in studies comparing TB with bacterial pneumonia patients. CONCLUSION The results suggest consistently acceptable sensitivity and specificity of the PCT test in distinguishing TB from bacterial pneumonia. However, given the imperfect sensitivity and specificity of the test, medical decisions should be based on both the PCT test results as well as on clinical findings.

Background: First-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are effective for the treatment of lung adenocarcinoma with an EGFR-sensitizing mutation, but resistance is inevitable. Chemotherapy is widely used in the second-line setting. The outcome following this treatment scheme has not been thoroughly evaluated. Methods: From 2007 to 2011, consecutive patients with mutated EGFR receiving first-line TKI and second-line chemotherapy were retrospectively reviewed. The overall response was categorized into double responder, single responder and double nonresponder. Results: Following this treatment scheme, baseline Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (HR 0.60; 95% CI 0.37-0.98; p = 0.041) and double responder (HR 0.24; 95% CI 0.07-0.78; p = 0.018) were independent predictors of overall survival. Absence of pleural metastasis independently predicted the response to first-line TKI (OR 2.60; 95% CI 1.13-5.99; p = 0.025). In TKI responders, ECOG performance status 0-1 before chemotherapy (OR 4.95; 95% CI 1.15-21.28; p = 0.006), an exon 19 deletion (OR 4.74; 95% CI 1.30-17.21; p = 0.018) and progression-free survival (PFS) on first-line TKI (OR 1.02; 95% CI 1.01-1.09; p = 0.049) independently predicted the response to second-line chemotherapy. A moderate linear relationship (Pearson's r = 0.441; p = 0.001) existed between the PFS of this treatment scheme in TKI responders. Conclusion: The status of double responder to first-line TKI and second-line chemotherapy was predictive of improved survival in EGFR-mutated adenocarcinoma.

Objectives: To present the complications of Ultraflex Self-Expandable Metallic Stents (SEMSs) applied in patients with benign tracheobronchial diseases. Methods: Eighty patients received 124 SEMSs were retrospectively reviewed in a tertiary hospital. Results: The baseline characteristics of patients received SEMS implantation including age (mean + standard deviation: 62.5 + 14.8 years), gender (male, 60.5%), smoking (46.8%), forced expiratory volume in first one second (FEV1) (mean + standard deviation, 0.92 +0.41 L/s), follow-up days after SEMS implantation (median (interquartile range); 457 (131 - 897)) and covered SEMS (33.9%) were listed. Symptoms improved after SEMS implantation among 95 patients (76.6%). Time to complications developed was 236 (median; interquartile range, 59 - 672) days. The overall complication rate was 41.9% after SEMS implantation. The complications included SEMS migration (6.5%), granuloma (19.3%) and SEMS fracture (16.1%). Successful management rates of SEMS migration, granuloma and SEMS fracture were up to 100%, 83.3%, and 85% respectively. Conclusions: Patients received SEMS implantation due to benign conditions had poor lung function and were old. The complication rate in patients with benign conditions was high after longer follow-up period, however, successful management achieved in most patients with complications.

Rationale: Myeloid-derived suppressor cells (MDSCs) are a heterogeneous family of myeloid cells that suppress T-cell immunity in tumor-bearing hosts. Their clinical relevance remains unclear.Objectives: To identify subtypes of myeloid-derived suppressor cells in patients with non–small cell lung cancer (NSCLC) and their clinical relevance.Methods: CD11b+CD14− and CD11b+CD14+ cells, determined and phenotyped by fluorescence-activated cell sorter analysis, in the peripheral blood mononuclear cells (PBMCs) of treatment-naive patients with advanced NSCLC were correlated with clinical data. T-cell activation in response to CD3/CD28 costimulation was determined by carboxy-fluorescein diacetate succinimidyl ester (CFSE) staining and ELISA analysis of IFN-γ. The percentage of CD11b+CD14+S100A9+ cells in PBMCs was correlated with and tested as a predictor for treatment response in a cohort of patients prospectively receiving first-line cisplatin-based chemotherapy.Measurements and Main Results: Patients with NSCLC...

Background. We studied the role of pulmonary veins in cancer progression using computed tomography (CT) scans.Methods. We obtained data from 260 patients with pulmonary vein obstruction syndrome (PVOS). We used CT scans to investigate pulmonary lesions in relation to pulmonary veins. We divided the lesions into central and peripheral lesions by their anatomical location: in the lung parenchymal tissue or pulmonary vein; in the superior or inferior pulmonary vein; and by unilateral or bilateral presence in the lungs.Results. Of the 260 PVOS patients, 226 (87%) had central lesions, 231 (89%) had peripheral lesions, and 190 (75%) had mixed central and peripheral lesions. Among the 226 central lesions, 93% had lesions within the superior pulmonary vein, either bilaterally or unilaterally. Among the 231 peripheral lesions, 65% involved bilateral lungs, 70% involved lesions within the inferior pulmonary veins, and 23% had obvious metastatic extensions into the left atrium. All patients exhibited nodules within their pulmonary veins. The predeath status included respiratory failure (40%) and loss of consciousness (60%).Conclusion. CT scans play an important role in following tumor progression within pulmonary veins. Besides respiratory distress, PVOS cancer cells entering centrally can result in cardiac and cerebral events and loss of consciousness or can metastasize peripherally from the pulmonary veins to the lungs.

Primary pulmonary lymphoepithelioma-like carcinoma is a very rare subtype of non-small-cell lung cancer. This retrospective study enrolled 21 patients and aimed to evaluate the long-term response under multimo- dality treatment. Primary pulmonary lymphoepithelioma-like carcinoma had a better prognosis compared with other non-small-cell lung cancers. Accurate pathologic diagnosis is recommended before cancer treatment. Introduction: Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is a very rare subtype of non-small-cell lung cancer. Most cases are reported in Southeast Asia and are associated with Epstein-Barr virus infections. Because of its rare incidence, the optimal treatment and the results of long-term follow-up are not well understood. This study is an attempt to discover the multimodality treatment results of the primary pulmonary LELC. Methods: This retrospective study enrolled 21 patients with primary pulmonary LELC treated at 2 hospitals with a multimodality approach, including surgery, chemotherapy, radiotherapy, and targeted therapy. Results: The median follow-up time is 5.9 years and the median survival is 6.4 years. The median overall survival for patients with stage III and with stage IV disease is 3.4 years. In early-stage primary pulmonary LELC, surgery and adjuvant chemotherapy provided good treatment outcome. Advanced primary pulmonary LELC is relatively more chemosensitive and radiosensitive. Conclusion: Patients with primary pulmonary LELC showed better prognosis than those with other types of non-small-cell lung cancer and achieved longer survival under multimodality treatment. This disease character is similar to that of nasopharyngeal carcinoma. Accurate pathologic diagnosis is recommended before the treatment. For advanced diseases, platinum-based doublet chemotherapy can be considered the first-line treatment. Radiation dose should consider tumor location, and 5000 to 7000 cGy is frequently applied for pulmonary LELC.

Introduction Esophagorespiratory fistula (ERF) caused by esophageal cancer has a poor prognosis. This study describes the clinical effects of airway ultraflex stenting as an alternative method for ERF caused by esophageal cancer. Methods In an university-affiliated hospital, consecutive patients with ERF caused by esophageal cancer and confirmed by bronchoscopy were included. The demography, clinical manifestations and survival between groups with and without airway stenting were compared by case-control study. Results From 2001 to 2007, 817 patients with esophageal cancer received bronchoscopy. Among these patients, 59 patients with ERF were included in this study. The demography and clinical manifestations between groups with and without airway stenting were similar, but survival improved in group with airway stenting, which was compared using log-rank test [ P = 0.04; hazard ratio, 0.56; 95% confidence interval (CI), 0.31–0.99]. After adjusted with age and gender by multinominal logistic regression, airway stenting [adjusted odds ratio (OR), 5.2; P = 0.01; 95% CI, 1.4–18.8], performance status (adjusted OR, 6.1; P = 0.004; 95% CI, 1.8–20.8), further treatment (adjusted OR, 8.7; P = 0.001; 95% CI, 2.3–32.8) and prolonged pneumonia (adjusted OR, 0.14; P = 0.008; 95% CI, 0.03–0.59) remained as significant factors that impacted survival. Conclusions Surgical treatment remains the first choice in patients with esophageal cancer with ERF; however, the authors provided an alternative airway stenting for those patients whom surgery is unsuitable. It improved survival in the group with airway stenting than those without. Performance status improvement and further treatment for esophageal cancer may improve survival, but prolonged pneumonia may worsen survival.

Research suggests that the semiquantitative determination of nodal (18)F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET)/computed tomography (CT) may be useful for the assessment of mediastinal metastases in patients with non-small-cell lung carcinoma (NSCLC). The aim of this study was to evaluate the diagnostic ability of using different standardized uptake value (SUV) parameters in the detection of ipsilateral mediastinal (N2) disease.A total of 102 patients newly diagnosed with non-small-cell lung carcinoma who underwent (18)F-FDG PET/CT before surgery and had not received prior therapy were retrospectively included. All patients underwent surgical resection of the primary tumor and mediastinal lymph node dissection. On a station-based analysis, different SUV parameters (eg, mediastinal lymph node SUV, node/aorta SUV ratio, and node/liver SUV ratio) were evaluated using the histopathologic results as the reference standard. The optimal cutoff value for each SUV parameter was determined with receiver-operating characteristic curve analysis.The areas under the receiver-operating characteristic curves were 0.674, 0.693, and 0.715 for node SUV, node/aorta SUV ratio, and node/liver SUV ratio, respectively (P.05). With cutoff values of 3.15, 1.37, and 1.02 for node SUV, node/aorta SUV ratio, and node/liver SUV ratio, respectively, the sensitivity of (18)F-FDG PET/CT for N2 staging was 57.1%, 85.7%, and 71.4%, and specificity was 74.2%, 50.5%, and 61.9%.Compared to node SUV alone, the use of node/aorta and node/liver SUV ratios resulted in improved detection of N2 metastases. The two SUV parameters may potentially improve the diagnostic accuracy of (18)F-FDG PET/CT for the diagnosis of N2 disease in patients with non-small-cell lung carcinoma.

Introduction Despite removal of airway metallic stents by rigid bronchoscope was presented, there are few reports describing such removal by flexible bronchoscope. Methods 36 patients who had airway Ultraflex stents removed by flexible bronchoscope from 2002 to 2009 were reviewed. Factors contributing to removal method and complications during and after removal were analyzed by multinomial logistic regression. Results Among 36 patients with stent extraction; 17 stents (47.2%) were removed by a single procedure and 19 (52.8%) by multiple procedures. There was no mortality or severe morbidity during or after stent removal. There were 21 complications after stent removal, including retained stent pieces (n = 9), mucosal tear with bleeding (n = 5), and re-obstruction requiring silicone stent placement (n = 7). Stent indwelling time > 10 months (adjusted odds ratio: 9.5; 95% confidence interval: 7.9–11.1, P=0.01), obstructive granulation tissue formation before stent removal (adjusted odds ratio: 5.2; 95% confidence interval: 2.2–8.6, P=0.01), and stent fracture before removal (adjusted odds ratio: 3.5; 95% confidence interval: 1.8–15.4, P=0.04) were independent predictors of the need for multiple procedures for stent removal. Stent indwelling time > 10 months (adjusted odds ratio: 4.2; 95% confidence interval: 2.1–8.9, P=0.01), obstructive granulation tissue formation before stent removal (adjusted odds ratio: 16.5; 95% confidence interval, 1.8–49.6, P=0.01), and multiple procedures required for removal (adjusted odds ratio: 6.9; 95% confidence interval, 1.1–43.5, P=0.04) were independent predictors of removal complications. Conclusions A flexible bronchoscope can be used to remove stents in patients with central airway obstruction and stent-related complications. This procedure should be performed in centers with experienced multidisciplinary teams.

Findings from the phase 3 FLEX study showed that the addition of cetuximab to cisplatin and vinorelbine significantly improved overall survival, compared with cisplatin and vinorelbine alone, in the first-line treatment of EGFR-expressing, advanced non-small-cell lung cancer (NSCLC). We investigated whether candidate biomarkers were predictive for the efficacy of chemotherapy plus cetuximab in this setting.Genomic DNA extracted from formalin-fixed paraffin-embedded (FFPE) tumour tissue of patients enrolled in the FLEX study was screened for KRAS codon 12 and 13 and EGFR kinase domain mutations with PCR-based assays. In FFPE tissue sections, EGFR copy number was assessed by dual-colour fluorescence in-situ hybridisation and PTEN expression by immunohistochemistry. Treatment outcome was investigated according to biomarker status in all available samples from patients in the intention-to-treat population. The primary endpoint in the FLEX study was overall survival. The FLEX study, which is ongoing but not recruiting participants, is registered with ClinicalTrials.gov, number NCT00148798.KRAS mutations were detected in 75 of 395 (19%) tumours and activating EGFR mutations in 64 of 436 (15%). EGFR copy number was scored as increased in 102 of 279 (37%) tumours and PTEN expression as negative in 107 of 303 (35%). Comparisons of treatment outcome between the two groups (chemotherapy plus cetuximab vs chemotherapy alone) according to biomarker status provided no indication that these biomarkers were of predictive value. Activating EGFR mutations were identified as indicators of good prognosis, with patients in both treatment groups whose tumours carried such mutations having improved survival compared with those whose tumours did not (chemotherapy plus cetuximab: median 17·5 months [95% CI 11·7-23·4] vs 8·5 months [7·1-10·8], hazard ratio [HR] 0·52 [0·32-0·84], p=0·0063; chemotherapy alone: 23·8 months [15·2-not reached] vs 10·0 months [8·7-11·0], HR 0·35 [0·21-0·59], p0·0001). Expression of PTEN seemed to be a potential indicator of good prognosis, with patients whose tumours expressed PTEN having improved survival compared with those whose tumours did not, although this finding was not significant (chemotherapy plus cetuximab: median 11·4 months [8·6-13·6] vs 6·8 months [5·9-12·7], HR 0·80 [0·55-1·16], p=0·24; chemotherapy alone: 11·0 months [9·2-12·6] vs 9·3 months [7·6-11·9], HR 0·77 [0·54-1·10], p=0·16).The efficacy of chemotherapy plus cetuximab in the first-line treatment of advanced NSCLC seems to be independent of each of the biomarkers assessed.Merck KGaA.

Objective Due to the shortage of cadaver liver grafts in Asia, more than 90% of biliary atresia (BA) patients require living donor liver transplantation (LDLT), but the factors that influence liver graft regeneration in pediatric patients are still unclear. The aim of this study was to evaluate the potential predisposing factors that encourage liver graft regeneration in pediatric liver transplantation (LT). Methods Case notes and Doppler ultrasound and computed tomography studies performed before and 6 months after transplantation of 103 BA patients who underwent LDLT were reviewed. The predisposing factors that triggered liver regeneration were compiled from statistical analyses and included the following: age, gender, body weight and height, spleen size, graft weight–to–recipient weight ratio (GRWR), post-transplantation total portal flow, and vascular complications. Results Seventy-two pediatric recipients were enrolled in this study. The liver graft regeneration rate was 29.633 ± 36.61% (range, −29.53–126.27%). The size of the spleen ( P = .001), post-transplantation portal flow ( P = .004), and age ( P = .04) were correlated lineally with the regeneration rate. The GRWR was negatively correlated with the regeneration rate ( P = .001) and was the only independent factor that affected the regeneration rate. When the GRWR was >3.4, patients tended to have poor and negative graft regeneration ( P = .01). Conclusion Large-for-size grafts have negative effect on regeneration rates because liver grafts that are too large can compromise total portal flow and increase vascular complications, especially when the GRWR is >3.4. Thus, optimal graft size is more essential than other factors in a pediatric LDLT patient.

ObjectiveSelf-expandable metallic stents are used to relieve airway stenosis in selected patients; however, fracture of these stents may occur. This analysis aims to investigate the extent of tracheal torsion, assessed by a computed-generated reformatted 3-dimensional tracheal reconstruction from 2-dimensional computed tomographic images in predicting fracture of tracheal self-expandable metallic stents.MethodsFrom 2001 to 2007, 32 patients (aged 62.8 ± 14.1 years) with benign tracheal diseases received chest computed tomographic evaluation and Ultraflex (Boston Scientific, Natick, Mass) self-expandable metallic stents. The bending angles of the central axis and peripheral wall of the trachea at choke point were measured from the computed-generated 3-dimensional tracheal images.ResultsSeventeen fractured stents were found among the patients. The median time for stent fracture was 865 days after implantation. Receiver operating characteristic curve analysis revealed that a 19° bending angle of the tracheal central axis (area under the curve, 0.929; 95% confidence interval, 0.847–1.012; P

Depressive symptoms are commonly experienced by cancer patients, especially those with advanced disease. The link between depression and survival outcome in cancer patients has received increasing attention. The purpose of this study was to determine, after adjusting the known covariates, whether the depressive symptoms during the first cycle of chemotherapy can predict the mortality of patients with advanced non-small cell lung cancer (NSCLC). Patients with stage III or IV NSCLC were recruited from a large teaching hospital located in northern Taiwan. Depressive symptoms were assessed during the first cycle of chemotherapy using the Hospital Anxiety and Depression Scale-Depression subscale. A cut-off of 7/8 was used to categorize patients into depressed and non-depressed groups. All patients were followed up until the end of the study. The follow-up time ranged from 10 to 30 months. The study sample consisted of 90 NSCLC patients. Twenty patients (22.2%) were categorized as depressed. The median survival time in the depressed group was significantly shorter than that of the non-depressed group (11.83 vs. 24.47 months, P = 0.017). After controlling for demographic and clinical factors, depressive symptoms remained significantly (p = 0.023) associated with a shorter survival time. Compared to the non-depressed group, the depressed group had twice the risk of death (HR = 2.18, 95% CI = 1.11 to 4.28). The finding supports that depressive symptoms at the early phase of treatment can predict shorter survival in patients with advanced NSCLC.

Monocytic myeloid-derived suppressor cells (MDSCs), particularly the S100A9+ subset, has been shown initial clinical relevance. However, its role in EGFR-mutated lung adenocarcinoma, especially to EGFR-tyrosine kinase inhibitor (EGFR-TKI) is not clear. In a clinical setting of EGFR mutated lung adenocarcinoma, a role of the MDSC apart from T cell suppression was also investigated.Blood monocytic S100A9In conclusion, blood S100A9Patients with activating EGFR mutation lung adenocarcinoma receiving first line EGFR TKIs were prospectively enrolled. Peripheral blood mononuclear cells (PBMCs) were collected for MDSCs analysis and for monocyte-derived macrophages (MDMs) and stored tissue for TAM analysis by IHC. A transwell co-culture system of MDMs/macrophages and H827 cells was used to detect the effect of macrophages on H827 and microarray analysis to explore the underlying molecular mechanisms, functionally confirmed by RNA interference.

Introduction Infection is a frequent cause of death in patients with systemic lupus erythematous (SLE) admitted to the intensive care unit (ICU). Complicated clinical features of SLE patients may delay or cause inadequate antimicrobial treatment. This study aimed to determine if inadequate antimicrobial treatment is an independent risk factor for mortality in SLE patients in the ICU. Methods Fifty-eight SLE patients admitted to the ICU were evaluated in a retrospective analysis. Inadequate antimicrobial treatment was defined by patient receiving antibiotics ≥24hours after the diagnostic criteria for nosocomial infection and/or the identified microorganism did not exhibit in vitro sensitivity to the antibiotics administered in the ICU. Results Multivariate logistic regression analysis identified the risk factors. Thirty-three (56.9%) SLE patients died during their ICU stay. The nonsurvivor group (n=33), exhibited lower platelet count ( P =0.025), prolonged hospital stay before ICU admission ( P =0.015), higher Acute Physiology and Chronic Health Evaluation II score ( P =0.015), and higher prevalence of multiple organ failure ( P =0.044) and inadequate antimicrobial treatment ( P =0.002) compared with the survivor group (n=25). In multivariate logistic regression analysis, inadequate antimicrobial treatment was the most significant factor for mortality (odds ratio=12.02, 95% confidence interval=1.24–116.10, P =0.032). Patients with prolonged hospitalization prior ICU admission had a mild risk for mortality (odds ratio=1.06, 95% confidence interval=1.00–1.12, P =0.045). Conclusions SLE patients in the ICU receiving inadequate antimicrobial treatment or with prior prolonged hospital stay have a higher risk of mortality. Clinical efforts should ensure adequate antimicrobial treatment in SLE patients with prior prolonged hospital stay before ICU admission.

Immune aberrations have been demonstrated in tumorogenesis, and myeloid-derived suppressor cells (MDSC) have shown to play a pivotal role in mediating immune suppression in animal models of human tumors. In the present study, we explored the clinical relevance of CD11b+/CD14⁻/CD15+/CD33+ MDSCs and the association of MDSCs with CD8+ cytotoxic T lymphocytes in patients with non-small-cell lung cancer (NSCLC).The population of CD11b+/CD14⁻ cells in peripheral blood mononuclear cells (PBMNC) was determined in 173 patients with NSCLC and 42 control subjects. The expression of CD15, CD33, IL-4R, INF-γR, iNOS and L-arginase were analyzed. Cocultures with CD8+ T lymphocytes and Jurkat cells were developed to determine the impact of MDSCs on the expression of CD3ζ of CD8+ T lymphocytes.Patients with treatment-naïve, advanced-stage NSCLC (n = 87) had an increased subpopulation of CD11b+/CD14⁻/CD15+/CD33+ cells in the PBMNCs with characteristics of MDSCs (P0.0001). The CD11b+/CD14⁻ cells in PBMNC also express IL-4R and INF-γR and can suppress CD3ζ expression in CD8+ T lymphocytes. The subpopulation of CD11b+/CD14⁻ cells in PBMNC was decreased in the advanced-stage NSCLC patients who had responsiveness to chemotherapy (n = 41, P0.0001) and in the early-stage NSCLC patients after removal of tumor (n = 8, P = 0.0391). Notably, a negative association existed between the population of CD11b+/CD14⁻ cells in PBMNC and the frequency of CD8+ T lymphocytes (n = 48, r = -0.3141, P = 0.0297).Our study provided evidence of an increased pool of CD11b+/CD14⁻/CD15+/CD33+ MDSCs in the peripheral blood of NSCLC patients. For the suppressive effect of the cells on CD8+ T lymphocytes, these findings suggest the important role of the CD11b+/CD14⁻/CD15+/CD33+ MDSCs in mediating immunosuppression in NSCLC.

Objective This retrospective study was to determine factors that contribute to self-expandable metallic stent fracture in patients with tracheobronchial disease. Methods From 2001 to 2006, 139 patients (age, 62.1 ± 15.4 years; range, 23–87 years) with benign (n = 62) and malignant (n = 77) tracheobronchial disease received 192 Ultraflex (Boston Scientific, Natick, Mass) self-expandable metallic stents (98 in patients with benign disease and 94 in patients with malignant disease). Results Seventeen fractured self-expandable metallic stents were found; the incidence was 12.2% (17/139 patients) among patients with tracheobronchial disease. Tortuous airway (odds ratio, 4.06; 95% confidence interval, 1.04–18.34; P = .04) independently predicted self-expandable metallic stent fracture. Most self-expandable metallic stent fractures (64.7%, 11/17) were detected 500 to 1000 days after self-expandable metallic stent implantation. Clinical presentations for patients with fractured self-expandable metallic stents included dyspnea exacerbation (70.6%, 12/17) and cough (23.5%, 4/17). Conclusions Self-expandable metallic stent fracture is not uncommon in patients with tracheobronchial disease. Tortuous airway is an independent predictor for it. Although management of the fractured self-expandable metallic stent in our study was feasible and safe, self-expandable metallic stents should be restricted to a more select population.

Summary Purpose Erlotinib is the first epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) which has demonstrated a survival benefit in non-small-cell lung cancer (NSCLC) patients. An open label phase II study was conducted in Taiwanese patients with NSCLC to evaluate its efficacy. Methods Patients with proven stage IIIB/IV NSCLC who had received at least one line of standard chemotherapy or radiotherapy were enrolled into this study. All patients were given oral erlotinib, 150 mg/day till disease progression. Results From May 2005 to July 2006, 300 patients were entered from 14 hospitals in Taiwan. This analysis was based on 299 patients who received at least one dose of erlotinib. The best response rates were a 29% partial response and 44% stable disease in 273 patients who had response data available. Non-smoking (p = 0.033), adenocarcinoma/BAC (p = 0.0027), female (p = 0.0013), aged less than 65 years (p = 0.0115), stage IV (p = 0.0492), patients with skin rash (p = 0.0216), and a higher grade of skin rash (p = 0.003) were significantly correlated with response to treatment. Skin rash was a common adverse event (any grade: 84%, Gr 3–4: 16%). The median time to disease progression was 5.6 months. Cox regression model for progression free survival showed patients most at risk of early progression were males of low performance status having squamous cell carcinoma. Conclusions This was the largest multicenter prospective clinical study of NSCLC in Taiwan. The results demonstrated the excellent response rates, time-to-progression and overall survival of erlotinib in a large population of Taiwanese NSCLC patients who had been previously treated with chemotherapy or radiotherapy.

Background/purposeThis study assessed how positive expiratory pressure (PEP) affected pulmonary function, functional capacity, and subjective cough difficulty in individuals with chronic obstructive pulmonary diseases (COPD).MethodsThis was a prospective, randomized, controlled study. Subjects were recruited from an outpatient department at a university hospital. Thirty-two patients with COPD were allocated to either PEP + FET (forced expiratory technique) group (n = 16) or FET only group (n = 16). Subjects in PEP + FET and FET groups were in a clinically stable condition before and during the study. Subjects in the PEP + FET group received PEP breathing using a mouth adjunct to FET, and the FET group was administered FET for 4 weeks only. Patients received weekly follow-up during the study period. Pulmonary function, 6-minute walk tests, and subjective cough difficulty scores were measured before and after the 4-week interventions.ResultsSubjects in the PEP + FET group had a significantly increased diffusing capacity (DLCO) compared to preintervention (p < 0.05) and after intervention in the FET group (p < 0.05). DLCO significantly increased in the PEP + FET group from 18.0 ± 7.3 to 20.1 ± 7.2 mL/min/mmHg. The 6-minute walking distance (6MWD) also increased significantly from 516.8 ± 94.1 to 570.6 ± 60.4 m in the PEP + FET group (p < 0.001) after intervention, compared to that for the FET group (p < 0.05). Additionally, the PEP + FET group had significantly lower cough difficulty scores compared to those at baseline and in the FET group.ConclusionFour-week PEP therapy as an adjunct to FET further enhanced DLCO and 6MWD, and reduced cough difficulty compared to FET only in COPD patients with mucus hypersecretion. [J Formos Med Assoc 2007;106(3):204-211]

Objectives. Chemotherapy as first-/second-line treatment in different epidermal growth factor receptor (EGFR) mutation lung adenocarcinoma remains controversial.Methods. Consecutive patients were collected between 2009 and 2012. Patients were divided into two groups (1st-line chemotherapy:n= 56 and 2nd-line chemotherapy:n= 55). Their outcomes profiles were analyzed.Results. The overall survival (OS) of all patients (390 versus 662 days,p< 0.0001), as well as both progression-free survival (PFS, 151 versus 252 days,p= 0.0001) and OS (308 versus 704 days,p= 0.0001) of patients withL858Rmutation (n= 63), who received 2nd-line chemotherapy, was significantly poor. By univariate and multivariate analysis, 2nd-line chemotherapy, andL858Rmutation were significantly related to poor PFS and OS.Conclusion. In advanced lung adenocarcinoma,L858Rmutation and 2nd-line chemotherapy caused a poor outcome. It is a consideration to choice of 1st-line chemotherapy in these subjects. A prospective design is warranted to confirm this finding.

Background/Purpose: This study was designed to investigate the effects of 6 months of nocturnal nasal positive pressure ventilation (NNPPV) on respiratory muscle function and exercise capacity in patients with chronic respiratory failure. Methods: A prospective, randomized, controlled design was used. Twenty-nine patients with chronic respiratory failure were enrolled and allocated to either the NNPPV (n = 14) or control group (n = 15). Patients in the NNPPV group received bi-level positive pressure ventilation via nasal mask for 6 consecutive months. Arterial blood gas, respiratory muscle assessment and 6-minute walk test (6MWT) were performed before and after the 6-month NNPPV intervention. Respiratory muscle function was assessed using the variables of maximal inspiratory pressure (Pimax), maximal expiratory pressure (Pemax), and maximum voluntary ventilation (MVV). Results: Subjects in the NNPPV group showed a significant improvement in blood gas exchange and increased 6-minute walk distance (6MWD) compared to baseline and the control group. The 6MWD was significantly increased from 257.1 ± 114.1 to 345.2 ± 109.9 m (34.3%) in the NNPPV group. NNPPV also significantly improved MVV and Pimax relative to baseline. MVV was significantly increased from 19.2 ± 6.5 to 22.3 ± 7.1 L/min (16.1%) in the NNPPV group (p < 0.05). Furthermore, there was a significant correlation between the magnitude of MVV improvement and 6MWD change. Conclusion: The 6-month NNPPV treatment significantly decreased the partial pressure of carbon dioxide and improved daytime respiratory muscle function, thus contributing to exercise-capacity increase in patients with chronic respiratory failure. [J Formos Med Assoc 2006;105(6):459–467]

Background In this study, we investigated the efficacy of continuous epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) administration in lung adenocarcinoma patients harboring favorable mutations regarding the progressive disease (PD) status with appearance of indolent new lesions. Methods From June 2010 to October 2012, 102 patients with lung adenocarcinoma, harboring favorable EGFR mutations and treated with EGFR-TKI were analyzed. Definite new lesions were detected during EGFR-TKI therapy, even though the primary target tumors were controlled. Results Of the 102 patients, 57 continued and 45 discontinued EGFR-TKI therapy. The median overall survival was 529 days for the discontinuation group and 791 days for the continuation group (p = 0.0197). Median survival time after the discontinuation of EGFR-TKI was 181 days and 115 days in the discontinuation and continuation groups, respectively (p = 0.1776), whereas median survival time after the appearance of indolent new lesions was 204 days and 262 days, respectively (p = 0.0237). Conclusion Continuous EGFR-TKI administration in favorable EGFR-mutative lung adenocarcinoma patients with controlled primary tumors did not hinder the survival benefit, despite the appearance of new lesions.

1. Theophylline possesses anti-inflammatory activities in asthma. We examined whether theophylline and agents that modulate cyclic AMP can determine the survival and proliferation of progenitor cells. 2. Progenitor cells from the blood of normal and asthmatic subjects were cultured for 14 days in methylcellulose with GM-CSF, stem cell factor, IL-3 and IL-5. Apoptosis was measured by flow cytometry of propidium-iodide-stained cells. 3. A greater number of colonies with a higher proportion of cells of eosinophil lineage from asthmatics compared to normal subjects were grown. Theophylline (at 5 and 20 micro g ml(-1)) significantly inhibited colony formation and increased apoptotic cells in asthmatics compared to control. Salbutamol (0.1, 1, 10 micro M), dibutyryl-cAMP (0.1, 1 mM) and rolipram (0.1, 1 mM), a phosphodiesterase IV inhibitor, also dose-dependently decreased colony numbers and increased apoptosis of progenitor cells from asthmatics. 4. There was no significant effect of theophylline, db-cAMP, salbutamol or rolipram on colony formation or the survival of progenitor cells from normal subjects. AMP did not affect the colony formation and apoptosis. Expression of Bcl-2 protein on progenitor cells of asthma was downregulated by theophylline, salbutamol, db-cAMP and rolipram. 5. Theophylline and rolipram decreased colony formation committed to the eosinophil lineage, together with an increase in apoptosis through an inhibition of Bcl-2 expression effects that may occur through cAMP. The anti-inflammatory properties of theophylline include an inhibition of circulating progenitor cells.

OBJECTIVE To investigate the effects of endogenous nitric oxide on hyperoxia and tumor necrosis factor-alpha-induced leukosequestration and proinflammatory cytokine release in rat airways. DESIGN Prospective, randomized, controlled animal study. SETTING Experimental laboratory. SUBJECTS Male Sprague-Dawley rats weighing 350-500 g. INTERVENTIONS The rats were pretreated with N(G)-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg) or saline intravenously 4-6 mins before intratracheal administration of tumor necrosis factor-alpha, 95% oxygen, or both, when the vasopressor effect of L-NAME had reached a plateau. MEASUREMENTS AND MAIN RESULTS Bronchoalveolar lavage fluid was recovered from the airway of rats after exposure to 95% oxygen and tumor necrosis factor-alpha for 6 hrs under ventilator support. Neutrophils in lavage fluid were isolated and examined for the inducible nitric oxide synthase expression by flow-cytometric assay. Tumor necrosis factor-alpha and interleukin-1 beta in lavage fluid were measured by enzyme-linked immunosorbent assay. The percentage of neutrophils in bronchoalveolar fluid was significantly higher in rats exposed to hyperoxia + tumor necrosis factor-alpha (29.7 +/- 12.5%) compared with rats with hyperoxia (16.3 +/- 1.2%), tumor necrosis factor-alpha (4.2 +/- 1.1%), or room air (5.0 +/- 1.8%) alone (p

Background Hepatocellular carcinoma (HCC) is the leading malignant tumor in Taiwan. The majority of HCC patients are diagnosed in late stages and therefore in eligible for potentially curative treatments. Locoregional therapy has been advocated as an effective treatment for patients with advanced HCCs. Purpose The aim of this study was to evaluate the outcomes of HCC downstaged patients after locoregional therapy to allow eligibility for liver transplantation. Methods and materials From January 2004 to June 2010, 161 patients with HCCs underwent liver transplantation including 51 (31.6%) who exceeded the University of California–San Francisco (UCSF) who had undergone successful locoregional therapy to be downstaged within these criteria. Among the downstaged patients, 48 (94.1%) underwent transarterial embolization; 7 (13.8%), percutaneous ethanol injection; 24 (47.1%), radiofrequency ablation; 15 (29.4%), surgical resection, and 34 (66.7%), combined treatment. Results The overall 1- and 5-year survival rates of all HCC patients (n = 161) were 93.2% and 80.5%. The overall 1- and 5-year survival rates of downstaged (n = 51) versus non-downstaged (n = 110) subjects were 94.1% versus 83.7% and 92.7% versus 78.9%, respectively (P = .727). There are 15 (9.2%) HCC recurrences. The overall 1- and 5-year tumor-free rates of all HCC patients were 94.8% and 87.2%. The overall 1- and 5-year tumor-free rates between downstaged versus non-downstaged patients were 93.9% and 90.1% versus 95.2% and 86.0%, respectively (P = .812). Conclusion Patients with advanced HCC exceeding the UCSF/Milan criteria can be downstaged to fit the criteria using locoregional therapy. Importantly, successfully downstaged patients who are transplanted show excellent tumor-free and overall survival rates, similar to fit-criteria group.

Purpose: Most of the patients with stage IIIA pN2 non-small cell lung cancer (NSCLC) develop recurrence after surgery. It is not clear whether post neoadjuvant chemotherapy tumor-associated macrophages is associated with recurrence. Patients and Methods: Stage IIIA pN2 NSCLC patients underwent cisplatin/docetaxel neoadjuvant chemotherapy and surgery were retrospectively enrolled. Immunohistochemical staining of CD68 was used to identify macrophages in surgical resected stored tissues. Results: The objective response rate of cisplatin/docetaxel was 68%, overall median disease-free survival (DFS) was 13.1 months and median overall survival (OS) 36.8. months. Multiple Cox regression analysis showed low total macrophage numbers and mediastinal lymph nodes downstaging were independent factors for longer DFS, whereas high islet/stromal macrophages ratio was an independent facto for OS. In patients downstaged to pN0, low total macrophage numbers was also associated with longer DFS. Conclusions: Low total macrophage number is an independent factor for better DFS in pN2 stage IIIA NSCLC patients receiving neoadjuvant chemotherapy and surgical resection, which association was kept in those downstaged to pN0. Further studies are warrant to confirm the predictive role of TAMs and their potential causative role in tumor recurrence.

Although malignant endobronchial mass (MEM) has poor prognosis, cryotherapy is reportedly a palliative treatment. Clinical data on postcryotherapy MEM patients in a university-affiliated hospital between 2007 and 2011 were evaluated. Survival curve with or without postcryotherapy chemotherapy and performance status (PS) improvement of these subjects were analyzed using the Kaplan-Meier method. There were 59 patients (42 males), with median age of 64 years (range, 51–76, and median performance status of 2 (interquartile range [IQR], 2-3). Postcryotherapy complications included minor bleeding (n=12) and need for multiple procedures (n=10), while outcomes were relief of symptoms (n=51), improved PS (n=45), and ability to receive chemotherapy (n=40). The survival of patients with chemotherapy postcryotherapy was longer than that of patients without such chemotherapy (median, 534 versus 106 days; log-rank test,P=0.007; hazard ratio, 0.25; 95% confidence interval, 0.10–0.69). The survival of patients with PS improvement postcryotherapy was longer than that of patients without PS improvement (median, 406 versus 106 days; log-rank test,P=0.02; hazard ratio, 0.28; 95% confidence interval, 0.10–0.81). Cryotherapy is a feasible treatment for MEM. With better PS after cryotherapy, further chemotherapy becomes possible for patients to improve survival when MEM caused dyspnea and poor PS.

Background Obstructive sleep apnoea (OSA) has recently been identified as a possible aetiology for chronic cough. The aim of this study was to compare the incidence of chronic cough between patients with and without OSA and the impact of continuous positive airway pressure (CPAP) treatment in resolving chronic cough. Methods Patients referred to the sleep laboratory from January 2012 to June 2012 were retrospectively enrolled. Clinical data, treatment course and resolution of chronic cough were analysed. Specifically, gastro-oesophageal reflux (GERD), upper airway cough syndrome, asthma, apnoea-hypopnoea index and the impact of CPAP treatment on chronic cough were assessed. Results A total of 131 patients were reviewed. The incidence of chronic cough in the OSA group was significantly higher than the non-OSA group (39/99 (39.4%) vs. 4/32 (12.5%), p = 0.005). Both GERD and apnoea-hypopnoea index were significantly associated with chronic cough in univariate analysis. After multivariate logistic regression, GERD was the only independent factor for chronic cough. Moreover, the resolution of chronic cough was more significant in the OSA patients with CPAP treatment compared with those not receiving CPAP treatment (12/18 (66.7%) vs. 2/21 (9.5%), p = 0.010). Conclusion The incidence of chronic cough was significantly higher in the OSA patients. In addition, CPAP treatment significantly improved chronic cough. Therefore, OSA may be a contributory factor to chronic cough.

Interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha released from alveolar macrophages (AM) in pulmonary tuberculosis (TB) are important in host defense against mycobacterial infection. Nitric oxide (NO) production is enhanced in AM of TB patients. We examined whether NO was implicated in (IL)-1beta and TNF-alpha synthesis by AM of TB patients. Purified AM were retrieved by bronchoalveolar lavage from 11 TB patients and 10 normal subjects, and were cultured with or without the NO inhibitor N(G)-monomethyl-L-arginine (L-NMMA). The release of IL-1beta and TNF-alpha, and expression of their messenger RNAs (mRNAs), were determined by enzyme-linked immunosorbent assay and Northern blot analysis. The release of IL-1beta and TNF-alpha was greater from AM of TB patients than from AM of normal subjects. L-NMMA inhibited nitrite, IL-1beta, and TNF-alpha production in TB patients. The mRNA expression for IL-1beta and TNF-alpha was upregulated in TB patients and was depressed by L-NMMA. Immunocytochemistry done with a monoclonal antibody against the p65 subunit of nuclear factor (NF)-kappaB showed that NF-kappaB was highly expressed and translocated to the nuclei of AM from TB patients, and was inhibited by L-NMMA. Inhibition of NF-kappaB by pyrrolidine dithiocarbamate attenuated IL-1beta and TNF-alpha synthesis. In conclusion, enhanced NO generation by AM of TB patients plays an autoregulatory role in amplifying the synthesis of proinflammatory cytokines, probably through NF-kappaB activation.

Summary Lung cancer metastatic to the gingiva is quite unusual. A total of 16 cases have been previously described in the English language medical literature. The case of a 49 year-old man with stage IV pulmonary adenocarcinoma is described in which two rapidly growing tumors with intermittent bleeding and tenderness were found over the maxillary gingiva during chemotherapy treatment. An excisional biopsy was performed and the presumptive diagnosis of metastatic adenocarcinoma was confirmed. Oral function, nutritional status, and quality of life improved after surgery.

Microvesicles (MV) in the blood stream are associated with distant metastasis in cancer. Platelet or endothelial cell-related MV actively participate in thrombogenesis, which is an important step in cancer metastasis. This study investigated the correlations between MV levels of platelet-poor plasma and distant metastasis in lung cancer.Platelet-poor plasma from 44 treatment-naive lung cancer (23 with distant metastasis) and 19 normal subjects was used to determine the levels of glycoprotein Iβ (CD42) + platelet MV (PMV), P-selectin (CD62P) + PMV, VE-cadherin (CD144) + endothelial MV (EMV), tissue factor (CD142) + MV, thrombin-antithrombin complex and vascular endothelial growth factor (VEGF).The level of CD142 + MV was significant (odds ratio 5.86, 95 % confidence interval 1.31-38.3) in predicting distant metastasis in lung cancer, and a cutoff value of 2.668 (after logarithm transformation) in the ROC curve had a specificity of 90 % and a sensitivity of 59 %. The presence of distant metastasis showed a significant correlation between CD144 + EMV and VEGF, but not between CD144 + EMV and CD42 + PMV or CD62P + PMV in lung cancer subjects.The finding of CD142 + MV in platelet-poor plasma may be useful for suggesting distant metastasis in lung cancer. In addition to thrombogenesis, interaction between VE-cadherin and VEGF may be needed for successful metastasis in lung cancer.

Bronchial hyper-responsiveness is a cardinal feature of asthma. To determine whether nasal continuous positive airway pressure (NCPAP) influences airway smooth muscle in response to exogenous stimuli, we examined the effect of NCPAP on aerosolized methacholine-induced bronchoconstriction in 16 stable asthmatic patients. The dose-response curve for each subject was measured by a log transformation and linear regression analysis as well as a formula fitted to the data points to obtain values for a (slope) and b (position). The PD20FEV1 significantly increased in patients receiving 8 cmH2O of NCPAP by one doubling dose compared with that in patients using sham pressure. NCPAP shifted the dose-response curves to be flatter, deviated upwards and to the right. The coefficient a, indicating bronchial reactivity, was significantly lower in patients receiving NCPAP. The coefficient b, indicating the bronchial sensitive threshold, was higher after applying NCPAP. In contrast, coefficients a and b did not change in subjects with sham pressure. NCPAP also significantly enhanced the bronchodilator effect of inhaled salbutamol in response to methacholine-induced bronchoconstriction. In summary, we have shown that NCPAP therapy improves bronchial smooth reactivity with an increase in PD20FEV1 and a reduction in the bronchial reactivity and bronchial sensitivity. Therefore, NCPAP may provide an adjuvant therapy in patients with acute bronchial asthma.