Chih Hsi Kuo

Diagnostic Value of EBUS-TBNA for Lung Cancer with Non-Enlarged Lymph Nodes: A Study in a Tuberculosis-Endemic Country

Background In tuberculosis (TB)-endemic areas, contrast-enhanced computed tomography (CT) and positron emission tomography (PET) findings of lung cancer patients with non-enlarged lymph nodes are frequently discrepant. Endobronchial ultrasound-guided transbronchial aspiration (EBUS-TBNA) enables real-time nodal sampling, and thereby improves nodal diagnosis accuracy. This study aimed to compare the accuracy of nodal diagnosis by using EBUS-TBNA, and PET. Methods We studied 43 lung cancer patients with CT-defined non-enlarged mediastinal and hilar lymph nodes and examined 78 lymph nodes using EBUS-TBNA. Results The sensitivity, specificity, positive predictive value, and negative predictive value of EBUS-TBNA were 80.6%, 100%, 100%, and 85.7%, respectively. PET had low specificity (18.9%) and a low positive predictive value (44.4%). The diagnostic accuracy of EBUS-TBNA was higher than that of PET (91% vs. 47.4%; p<0.001). Compared to CT-based nodal assessment, PET yielded a positive diagnostic impact in 36.9% nodes, a negative diagnostic impact in 46.2% nodes, and no diagnostic impact in 16.9% nodes. Patients with lymph nodes showing negative PET diagnostic impact had a high incidence of previous pulmonary TB. Multivariate analysis indicated that detection of hilar nodes on PET was an independent predictor of negative diagnostic impact of PET. Conclusion In a TB-endemic area with a condition of CT-defined non-enlarged lymph node, the negative diagnostic impact of PET limits its clinical usefulness for nodal staging; therefore, EBUS-TBNA, which facilitates direct diagnosis, is preferred.

Feasibility of Bispectral Index-Guided Propofol Infusion for Flexible Bronchoscopy Sedation: A Randomized Controlled Trial

Objectives There are safety issues associated with propofol use for flexible bronchoscopy (FB). The bispectral index (BIS) correlates well with the level of consciousness. The aim of this study was to show that BIS-guided propofol infusion is safe and may provide better sedation, benefiting the patients and bronchoscopists. Methods After administering alfentanil bolus, 500 patients were randomized to either propofol infusion titrated to a BIS level of 65-75 (study group) or incremental midazolam bolus based on clinical judgment to achieve moderate sedation. The primary endpoint was safety, while the secondary endpoints were recovery time, patient tolerance, and cooperation. Results The proportion of patients with hypoxemia or hypotensive events were not different in the 2 groups (study vs. control groups: 39.9% vs. 35.7%, p = 0.340; 7.4% vs. 4.4%, p = 0.159, respectively). The mean lowest blood pressure was lower in the study group. Logistic regression revealed male gender, higher American Society of Anesthesiologists physical status, and electrocautery were associated with hypoxemia, whereas lower propofol dose for induction was associated with hypotension in the study group. The study group had better global tolerance (p<0.001), less procedural interference by movement or cough (13.6% vs. 36.1%, p<0.001; 30.0% vs. 44.2%, p = 0.001, respectively), and shorter time to orientation and ambulation (11.7±10.2 min vs. 29.7±26.8 min, p<0.001; 30.0±18.2 min vs. 55.7±40.6 min, p<0.001, respectively) compared to the control group. Conclusions BIS-guided propofol infusion combined with alfentanil for FB sedation provides excellent patient tolerance, with fast recovery and less procedure interference. Trial Registration ClinicalTrials. gov NCT00789815

Subsequent Chemotherapy Improves Survival Outcome in Advanced Non–Small-Cell Lung Cancer With Acquired Tyrosine Kinase Inhibitor Resistance

BACKGROUND Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) provide promising effect against non-small-cell lung cancer (NSCLC), although most tumors acquire resistance. Our objective was to assess the survival outcome of patients with NSCLC with or without subsequent chemotherapy after acquired TKI resistance. PATIENTS AND METHODS A total of 114 patients with pathologically confirmed stage IIIB or IV NSCLC who had had disease control with TKIs were retrospectively reviewed. After acquired TKI resistance, patients received either best supportive care (BSC) only or BSC plus subsequent chemotherapy. Both groups were well balanced in regard to performance status, age, sex, histology subtype, and smoking status. RESULTS Sixty-seven patients (58.8%) received subsequent chemotherapy, and 47 patients (41.2%) received BSC only. The median overall survival (OS) and progression-free survival (PFS) from the time of TKI resistance in the subsequent-chemotherapy group (11.2 months and 3.5 months, respectively) were longer than those of the BSC group (3.8 months and 1.5 months, respectively; P < .01). Patients who subsequently received taxane-based chemotherapy exhibited higher a response rate and disease control rate (48.7% and 79.5%, respectively) than patients treated with a nontaxane regimen (21.4% and 53.5%, respectively; P < .05). Overall survival and PFS in patients after taxane-based subsequent chemotherapy (12.7 months and 5.1 months, respectively) were longer than those of patients given a nontaxane regimen (7 months and 1.8 months, respectively; P < .01). CONCLUSION This study suggests that acquired TKI resistance should be managed aggressively. The higher antitumor response and survival outcome with a taxane-based regimen in this retrospective study could encourage further prospective investigation to confirm the efficacy of taxane over nontaxane chemotherapy in patients with NSCLC whose disease progresses with EGFR TKI treatment.

Low-dose weekly docetaxel is as tolerable as pemetrexed in previously treated advanced non-small-cell lung cancer.

Objectives: Docetaxel and pemetrexed have been validated as therapeutics for previously treated advanced non-small-cell lung cancer (NSCLC), but tolerability is a concern for standard treatment with docetaxel administered once every 3 weeks (tri-weekly 75-mg/m2 schedule). We conducted this retrospective study to compare the efficacy and toxicity of weekly low-dose docetaxel versus tri-weekly pemetrexed for previously treated advanced NSCLC. Methods: Consecutive patients who received low-dose single docetaxel (30 mg/m2 on days 1 and 8 every 3 weeks) or pemetrexed (500 mg/m2 every 3 weeks) at a single university-affiliated hospital following failure of previous treatment were retrospectively reviewed. Their outcomes and toxicity profiles were determined. Results: 179 patients were included between 2005 and 2008 (docetaxel, n = 79; pemetrexed, n = 100). Both groups had similar hematologic (16.5 vs. 15.0%; p = 0.84) and non-hematologic (20.3 vs. 24%; p = 0.55) toxicities. After controlling for confounding factors, docetaxel remained superior to pemetrexed for progression-free survival (median 4.0 vs. 2.4 months; hazard ratio 0.64; 95% CI 0.47–0.87; p = 0.005) and overall survival (median 15.0 vs.8.5 months; hazard ratio 0.54; 95% CI 0.38–0.77; p <0.001). Conclusion: Although this study showed that weekly low doses of docetaxel were as tolerable as pemetrexed for previously treated advanced NSCLC, a prospective design is needed to confirm this finding.

Endobronchial ultrasound-guided transbronchial biopsy and brushing: a comparative evaluation for the diagnosis of peripheral pulmonary lesions

OBJECTIVES The diagnosis of peripheral pulmonary lesions (PPLs) often involves endobronchial ultrasound (EBUS)-guided transbronchial biopsy (TBB), washing and brushing. Certain echoic features of PPL have been associated with biopsy yield. This study compared yields of TBB and bronchial washing (TBBW) with those of TBBW plus bronchial brushing and analysed the associations between clinical and echoic features and yield. METHODS We performed a retrospective review of 271 patients undergoing TBB for PPL. TBBW was performed in 139 patients and 132 underwent TBBW plus brushing. RESULTS The diagnostic yield of TBBW plus brushing was superior to that of TBBW (80.3 vs 66.2%, P < 0.01). In TBBW patients, lesions <3 cm (57.1 vs 73.7%, P < 0.05), EBUS probe adjacent to the lesion (47.6 vs 74.2%, P < 0.01), continuous margin (56.5 vs 75.7%, P < 0.01) and homogeneous echogenicity (51.0 vs 75.0%, P < 0.01) predicted lower yields, but adding bronchial brushing rendered the diagnostic yields similar, irrespective of EBUS echoic features, leaving lesion size of <3 cm (odds ratio 2.81; 95% confidence interval 1.08-7.31, P < 0.05) as the single independent predictor of lower yield by multivariate regression analysis. TBB plus brushing was not inferior to TBBW plus brushing (78.8 vs 80.3%, P = 0.88). CONCLUSIONS Bronchial brushing boosted diagnostic yields, particularly for PPLs with echoic features previously associated with a reduced biopsy yield.

Chronic cough and obstructive sleep apnoea in a sleep laboratory-based pulmonary practice

BackgroundObstructive 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.MethodsPatients 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.ResultsA 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).ConclusionThe 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.

Amplified Mycobacterium tuberculosis direct test for diagnosing tuberculous pleurisy--a diagnostic accuracy study.

Background The study was designed to investigate the clinical usefulness of Amplified Mycobacterium Tuberculosis Direct (AMTD) tests for diagnosing TB pleurisy. Methods One hundred and fifty-two patients for whom the exclusion of tuberculous pleural effusion was necessary were retrospectively analyzed. Results The sensitivity of AMTD in diagnosing pleural TB was 36.4% (20 of 55). Combining sputum and pleural effusion AFB smear, pleural biopsy, and AMTD test of pleural effusion increased sensitivity to 82.5% (33/40). There were significantly higher percentages of neutrophils in the pleural effusion in the positive than in the negative AMTD group (38.0±6.7% vs. 11.1±3.7%, p<0.001). Patients with symptom duration <18 days prior to pleural effusion studies had more positive AMTD tests than those with symptom >18 days (70% vs. 31.4%; OR 5.09; 95% CI 1.54–16.79; p = 0.011). Conclusions Combining AMTD tests with conventional diagnostic methods offer good sensitivity for pleural TB diagnosis. Patients in the early course of the disease are better candidates for AMTD tests.

Roles of EBUS-TBNA in non-small cell lung cancer

Background:  Endobronchial ultrasound‐guided transbronchial aspiration (EBUS‐TBNA) has the potential to improve nodal diagnosis and staging in non–small cell lung cancer (NSCLC). This study was performed to explore the roles of EBUS‐TBNA in NSCLC.

The safety and efficacy of alfentanil-based induction in bronchoscopy sedation: A randomized, double-blind, controlled trial

Background: Alfentanil in combination with propofol produces a synergistic sedative effect in patients undergoing flexible bronchoscopy (FB). However, the use of this combination is controversial due to the risk of cardiopulmonary depression. The aim of this study was to evaluate the proper induction regimen of alfentanil in propofol target-controlled infusion for FB sedation. Methods: One hundred seventy-three patients were assigned randomly into 5 regimens: Group 1 and 2, alfentanil 2.5 and 5 &mgr;g/kg, respectively, immediately before propofol administration; Group 3 and 4, alfentanil 2.5 and 5 &mgr;g/kg, respectively, 2 minutes before propofol administration; and Group 5, propofol administration alone to achieve the observer assessment of alertness and sedation scale 3∼2. The bronchoscopists, physicians in charge of sedation, and patients were blind to the regimens. Adverse events, drug dose, induction, procedure and recovery time, cough severity, and propofol injection related pain were recorded. Results: The patients in groups 2 and 4 required a lower dose of propofol (P = 0.031 and 0.019, respectively) and shorter time (P = 0.035 and 0.010) than group 5 for induction. Patients in group 2 experienced more hypoxemia than those in group 5 during induction (P = 0.031). The physician in charge of sedation scored a lower severity of cough in the patients in group 4 than in groups 3 and 5. There were no differences in terms of propofol injection related pain among the groups. Conclusion: Alfentanil 5 &mgr;g/kg given immediately before propofol infusion cannot be recommended. Further study is required to define conclusions about alfentanil 2.5 and 5 &mgr;g/kg because of the low power rating of subgroup in the present study.

Capnography monitoring the hypoventilation during the induction of bronchoscopic sedation: A randomized controlled trial

We hypothesize that capnography could detect hypoventilation during induction of bronchoscopic sedation and starting bronchoscopy following hypoventilation, may decrease hypoxemia. Patients were randomized to: starting bronchoscopy when hypoventilation (hypopnea, two successive breaths of at least 50% reduction of the peak wave compared to baseline or apnea, no wave for 10 seconds) (Study group, n = 55), or when the Observer Assessment of Alertness and Sedation scale (OAAS) was less than 4 (Control group, n = 59). Propofol infusion was titrated to maintain stable vital signs and sedative levels. The hypoventilation during induction in the control group and the sedative outcome were recorded. The patient characteristics and procedures performed were similar. Hypoventilation was observed in 74.6% of the patients before achieving OAAS < 4 in the control group. Apnea occurred more than hypopnea (p < 0.0001). Hypoventilation preceded OAAS < 4 by 96.5 ± 88.1 seconds. In the study group, the induction time was shorter (p = 0.03) and subjects with any two events of hypoxemia during sedation, maintenance or recovery were less than the control group (1.8 vs. 18.6%, p < 0.01). Patient tolerance, wakefulness during sedation, and cooperation were similar in both groups. Significant hypoventilation occurred during the induction and start bronchoscopy following hypoventilation may decrease hypoxemia without compromising patient tolerance.