Yueh-Fu Fang

Flexible Bronchoscopy with Multiple Modalities for Foreign Body Removal in Adults

Objectives Aspiration of the lower airways due to foreign body is rare in adults. This study aimed to determine the outcome of patients who received flexible bronchoscopy with different modalities for foreign body removal in the lower airways. Patients and Methods Between January 2003 and January 2014, 94 patients diagnosed with foreign body in the lower airways underwent flexible bronchoscopy with different modalities, which included forceps, loop, basket, knife, electromagnet, and cryotherapy. The clinical presentation, foreign body location and characteristics, and applications of flexible bronchoscopy were analyzed. Results Forty (43%) patients had acute aspiration, which developed within one week of foreign body entry and 54 (57%) had chronic aspiration. The most common foreign bodies were teeth or bone. More patients with chronic aspiration than those with acute aspiration were referred from the out-patient clinic (48% vs. 28%), but more patients with acute aspiration were referred from the emergency room (35% vs. 6%) and intensive care unit (18% vs. 2%). Flexible bronchoscopy with different modalities was used to remove the foreign bodies (85/94, 90%). Electromagnet or cryotherapy was used in nine patients to eliminate the surrounding granulation tissue before foreign body removal. In the nine patients with failed flexible bronchoscopy, eight underwent rigid bronchoscopy instead and one had right lower lung lobectomy for lung abscess. Conclusions Flexible bronchoscopy with multiple modalities is effective for diagnosing and removing foreign bodies in the lower respiratory airways in adults, with a high success rate (90%) and no difference between acute and chronic aspirations.

The role of the high-sensitivity C-reactive protein in patients with stable non-cystic fibrosis bronchiectasis.

Study Objectives. The aim of this study is to investigate the correlation between serum high-sensitivity C-reactive protein (hs-CRP) and other clinical tools including high-resolution computed tomography (HRCT) in patients with stable non-CF bronchiectasis. Design. A within-subject correlational study of a group of patients with stable non-CF bronchiectasis, who were recruited from our outpatient clinic, was done over a two-year period. Measurements. Sixty-nine stable non-CF bronchiectasis patients were evaluated in terms of hs-CRP, 6-minute walk test, pulmonary function tests, and HRCT. Results. Circulating hs-CRP levels were significantly correlated with HRCT scores (n = 69, r = 0.473, P < 0.001) and resting oxygenation saturation (r = −0.269, P = 0.025). HRCT severity scores significantly increased in patients with hs-CRP level of 4.26 mg/L or higher (mean ± SD 28.1 ± 13.1) compared to those with hs-CRP level less than 4.26 mg/L (31.7 ± 9.8, P = 0.004). Oxygenation saturation at rest was lower in those with hs-CRP level of 4.26 mg/L or higher (93.5 ± 4.4%) compared to those with hs-CRP level less than 4.26 mg/L (96.4 ± 1.6%, P = 0.001). Conclusion. There was a good correlation between serum hs-CRP and HRCT scores in the patients with stable non-CF bronchiectasis.

Advanced primary pulmonary lymphoepithelioma-like carcinoma: clinical manifestations, treatment, and outcome.

BACKGROUND Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is rare, with better clinical outcomes than other lung cancers. However, reports on advanced LELC characteristics and prognosis are lacking. METHODS This retrospective study included adults diagnosed with advanced LELC (at least stage IIIA) between January 2003 and December 2015. Clinical characteristics, treatment modalities, and outcomes were recorded. RESULTS Study population comprised 23 patients with a mean age of 63.7±10.6 years. The Eastern Cooperative Oncology Group status on diagnosis was 0 in five patients and 1 in the others. Most patients received multimodality treatment and all received cisplatin-based chemotherapy. Median follow-up duration was 28.8 months. The median progression free survival (PFS) was 14.6 months in patients received palliative chemotherapy. There were nine (39.1%) deaths. The median overall survival (OS) was not achieved. Until July 31, 2016, median OS was 54.1 months for stage IIIB and 27.6 months for stage IV. There was no significant difference in OS among all stages. No prognostic factors were found. CONCLUSIONS Advanced LELC responded well to cisplatin-based chemotherapy and/or radiotherapy. Main tumor resection is probably beneficial for advanced LELC. Long-term survival is possible for advanced LELC after multimodality treatment.

Prognostic implication of EGFR gene mutations and histological classification in patients with resected stage I lung adenocarcinoma

Introduction The prognostic value of epidermal growth factor receptor (EGFR) mutations and the correlation between EGFR mutations and the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) histological classification remain controversial. The current study aimed to investigate the pure prognostic role of EGFR mutations in treatment-naïve patients with resected stage I lung adenocarcinoma. Methods We retrospectively reviewed 373 patients with stage I pulmonary non-small-cell lung cancer who underwent complete surgical resection between January 2010 and May 2014. The tumors were classified according to IASLC/ATS/ERS criteria. EGFR mutation status was determined by established methods. Results A total of 120 patients were included for analysis; 87 had tumors with EGFR mutations and 33 had wild-type tumors. More low- and intermediate-grade tumors had EGFR mutations, and nearly half of the high-grade tumors were wild-type (75.7% versus 46.2%, p = 0.041). Patients with low-grade tumors had significantly greater median disease-free survival (DFS) (76.8 versus 13 months, p < 0.0001) and better overall survival (OS) (median OS not reached, p = 0.0003) than those with intermediate- and high-grade tumors. Tumor recurrence was 41.4% and 30.3% in mutant and wild-type patients. The 5-years survival rate was 54% and 71.2%. Multivariate analysis revealed that the new histological classification and the pathologic stage were independent predictors of both DFS and OS. EGFR mutation status had no prognostic implications. Conclusion Low grade tumors according to IASLC/ATS/ERS histological classification and the pathologic stage IA tumors of resected stage I lung adenocarcinomas independently predict better DFS and OS. EGFR mutations were frequently seen in histologically low- and intermediate-grade tumors but not a prognostic factor.

Distance-saturation product of the 6-minute walk test predicts mortality of patients with non-cystic fibrosis bronchiectasis

Background Previous surveillance methods to monitor the prognoses of patients with bronchiectasis are too complex for use in daily practice. The 6-minute walk test (6MWT) is a simple exercise test to predict the prognosis of chronic obstructive airway disease and numerous chronic lung diseases, including idiopathic pulmonary fibrosis. No studies have investigated exercise-induced oxygen desaturation (EID) and distance-saturation product (DSP) of 6MWT to predict the prognoses of patients with bronchiectasis. Methods This was a prospective study to identify correlations between variables of 6MWT and mortality in patients with bronchiectasis over a 6-year period. The study cohort included 69 patients with stable non-cystic fibrosis (non-CF) bronchiectasis who were regularly evaluated for functional status via 6-minute walk distance (6MWD), spirometry, BODE index, EID, and DSP. Results Of the 69 patients, 9 (13%) died and 60 (87%) survived during the 6-year follow-up period. The percentage of EID was higher [7 of 9 patients (78%) vs. 22 of 60 patients (27%), P=0.003] in the non-survivors group. The 6MWD (467.9±77.1 vs. 363.7±126.7 m, P=0.001) was higher in the survivors group. DSP was significantly lower in the non-survivors group (411.0±78.4 vs. 283.9±90.0 m%, P<0.001). Multivariate analysis showed that DSP (OR =0.983; 95% CI: 0.974-0.993, P=0.001) was the best parameter of 6MWT to predict mortality. Patients with a lower DSP of <280 m% were at a 66.5-fold greater risk (OR =66.5; 95% CI: 9.4-469.2) of 6-year mortality compared with those with DSP >280 m% (P<0.001). Conclusions DSP is a simple parameter to predict 6-year mortality in patients with non-CF bronchiectasis.

Abstract 2940: The p53 mutation R273H contributed to drug resistance of EGFR tyrosine kinase inhibitors

Tyrosine kinase inhibitors (TKIs) of epidermal growth factor receptor (EGFR) were the standard first-line treatments for lung cancers with activating EGFR mutations. Emergent drug resistance is the major problem in the patients who received treatment of EGFR TKIs. Second point mutation T790M mutations could be found in 50-60% patients who had drug resistance to EGFR TKIs. Alternative pathway of Met signaling, transformation to small cell lung cancer, over-expression of other HER family receptors or epithelial mesenchymal transit were reported in these patients who had drug resistance to EGFR TKIs. NFKB pathway played a role of early resistance to EGFR TKIs in the patients. The p53 mutation could be found in 70-80% lung adenocarcinoma patients. These mutations could be found in lung cancer patients who had wild type or mutated EGFR. Lung adenocarcinomas with mutated p53 lose tumor suppressor function of wild type p53 and have new function from mutated p53. We thought p53 mutation may have gain of function and result in drug resistance to EGFR TKIs in lung cancer patients. We knocked down p53 in three cancer cell line, MDA-MB-468 (p53 R273H), BT-549 (p53 R249S) and H322 (p53 R248L). We found knockdown of p53 R273H in MDA-MB-468 increased sensitivity to gefitinib. Knockdown of p53 R249S and p53 R248L showed the same response to gefitinib in cancer cell lines BT-549 and H322. Lung cancer cell line HCC827 had EGFR exon 19 deletion and was sensitive to gefitinib. We overexpressed p53 R273H, p53 R157H and p53 R249S in HCC827 lung cancer cell line. Overexpression of p53 R273H increased resistance to gefitinib in HCC827 lung cancer cell line. Overexpression of p53 R157H and p53 R249S did not increased the resistance to gefitinib. Conclusion: Gain of function of p53 R273H increased resistance to EGFR TKIs in cancer cell lines. Further immunohistochemistry staining and gene analysis of mutated p53 will be done in lung adenocarcinoma from lung cancer patients who received EGFR TKIs. Citation Format: Yueh-Fu Fang, Chun-Yu Lin, Peichih Lee. The p53 mutation R273H contributed to drug resistance of EGFR tyrosine kinase inhibitors. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2940.

The Association of Atopy, Total IgE, and Pulmonary Function in Bronchiectasis

Background: Bronchiectasis is characterized by irreversible airway dilation and destruction, but its clinical features relative to atopy and sensitized allergens remain unclear. Therefore, this study aimed to investigate the relationship between atopy, serum IgE level, and lung function in bronchiectasis patients.Method: The study included 114 adult patients with a clinical diagnosis of bronchiectasis between January 2001 and December 2009. They were all evaluated for allergen specific-IgE levels, serum total IgE and eosinophilic cationic protein (ECP) levels, spirometry values of the pulmonary function test, and high-sensitivity C-reactive protein (hs-CRP) levels. Atopy was defined as the presence of a specific IgE to 1 or more allergens.Results: Of the 114 adult bronchiectasis patients, 33 (28.9%) showed positive specific immunoglobulin E (IgE) levels to 1 or more allergens and were assessed as atopic. Atopic patients with bronchiectasis had worse pulmonary function parameters, in terms of forced expiratory volume in 1 second (FEV1) and FEV1/FVC (forced vital capacity) ratio, and higher levels of total serum IgE. There was a significant decrease in the pulmonary function test of atopic subjects with a positive specific-IgE response to more than 2 allergens, but not in those with only 1 or 2 positive allergens. There were higher serum total IgE levels in patients with more positive allergen-specific IgE tests. Bronchiectatic patients with a high total IgE level (≥100 kU/L) had significantly worse lung function (FEV1% predicted and FEV1/FVC ratio) and more sensitized allergens than those with a normal IgE level (＜100 kU/L).Conclusion: The existence of atopy with more sensitized allergens or higher total serum IgE levels may lead to a worse pulmonary function in patients with bronchiectasis. This may be due to IgE-mediated local and systemic inflammation.

Late-onset Central Alveolar Hypoventilation Syndrome in a Patient with Hemorrhagic Brainstem Lesion: Improvement after Medroxyprogesterone Treatment

Central hypoventilation syndrome, a rare condition, is defined as the failure of the automatic control of breathing. Secondary central hypoventilation syndrome should be distinguished from congenital central hypoventilation syndrome by the abnormalities in the brainstem, the place of respiratory control. Patients with this syndrome manifest hypoventilation during sleep, sometimes accompanied by hypoventilation during periods of wakefulness. Patients also lack a ventilatory response to hypercapnia and progressive hypoxia. We report the case of a 57-year-old woman who presented with chronic alveolar hypoventilation syndrome secondary to a brainstem lesion. The initial manifestation was a sense of dyspnea during sleep, and daytime sleepiness. The ventilatory response to CO2 was markedly decreased. She was treated successfully with a central stimulator (oral medroxyprogesterone 30 mg per day). We concluded that central alveolar hypoventilation should be highly suspected in patients with hypercapnia and a brainstem lesion, which can-be treated with a central stimulant.