Tzu-Hsiu Tsai

Ultrasonographic Evaluation of Liver/Spleen Movements and Extubation Outcome

INTRODUCTION The diaphragm plays a pivotal role in weaning and successful extubation. We hypothesized that ultrasonographic evaluation of the movements of the diaphragm by measuring liver/spleen displacement during spontaneous breathing trials is a good predictor for extubation outcome. PATIENTS AND METHODS The studied subjects were intubated patients receiving mechanical ventilation who were scheduled to be extubated. The displacement of liver/spleen was measured by ultrasonography before extubation. The patients were classified into a success group (SG) or failure group according to the extubation outcome. The baseline data and organ displacements in these two groups were analyzed. The sensitivity and specificity for the mean organ displacements and weaning parameters to predict successful extubation were calculated. RESULTS We included 55 patients, 32 of whom (58%) were in the SG. The baseline data are similar for these two groups, but the mean values of liver and spleen displacements were higher in the SG. Using a cutoff value of 1.1 cm, the sensitivity and specificity to predict successful extubation were 84.4% and 82.6%, respectively, better than traditional weaning parameters in this study. CONCLUSION The displacement of the liver/spleen, measured by ultrasonography, is a good predictor for extubation outcome.

Arrival of Klebsiella pneumoniae carbapenemase (KPC)-2 in Taiwan

Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan

Clinical and the Prognostic Characteristics of Lung Adenocarcinoma Patients with ROS1 Fusion in Comparison with Other Driver Mutations in East Asian Populations

Introduction: The prevalence, demographic features, and clinical outcomes of lung adenocarcinoma patients with novel ROS1 oncogenic rearrangement in East Asian populations are not clear. This study aimed to investigate the clinical and prognostic characteristics of lung adenocarcinoma in patients with ROS1 fusion compared with other driver mutations. Methods: Multiplex reverse transcription-polymerase chain reaction was used to detect the ROS1 fusion gene in lung adenocarcinoma cases. Immunohistochemistry was used to confirm the expression of ROS1. The demographic data and clinical outcomes of patients with the ROS1 fusion gene were compared with those of patients without the ROS1 fusion gene, including those with the EGFR mutation, EML4-ALK fusion, KRAS mutation, and quadruple-negative patients. Results: Of 492 patients with lung adenocarcinoma, 12 (2.4%) had the ROS1 fusion gene. Their median age was 45.0 years, significantly younger than that of the ROS1 fusion-negative cohorts (p < 0.001). Acinar (including cribriform) and solid patterns were the two most common histologic subtypes in the ROS1 fusion tumors (7 of 12, 58.3%) and were predominantly seen in CD74-ROS1 fusion tumors (66.7%). There was no significant survival difference between the ROS1 fusion-positive and ROS1 fusion-negative cohorts in surgical group, but ROS1 fusion-positive patients might have worse outcomes than EGFR-mutant patients in the stage IV group. Conclusions: The ROS1 fusion gene can be successfully detected in East Asian patients with lung adenocarcinoma using multiplex reverse transcription-polymerase chain reaction. These patients tend to be younger and have characteristic histologic subtypes. Due to the small number of ROS1 fusion patients, the prognostic value of ROS1 fusion need further studies to confirm.

RNA is favourable for analysing EGFR mutations in malignant pleural effusion of lung cancer

Malignant pleural effusion (MPE) is a useful specimen allowing for the evaluation of EGFR status in nonsmall cell lung cancer (NSCLC). However, direct sequencing of genomic DNA from MPE samples was found not to be sensitive for EGFR mutation detection. To test whether EGFR analysis from RNA is less prone to interference from nontumour cells that have no or lower EGFR expression, we compared three methods (sequencing from cell-derived RNA versus sequencing and mass-spectrometric analysis from genomic DNA), in parallel, for EGFR mutation detection from MPE samples in 150 lung adenocarcinoma patients receiving first-line tyrosine kinase inhibitors (TKIs). Among these MPE samples, EGFR mutations were much more frequently identified by sequencing using RNA than by sequencing and mass-spectrometric analysis from genomic DNA (for all mutations, 67.3 versus 44.7 and 46.7%; for L858R or exon 19 deletions, 61.3 versus 41.3 and 46.7%, respectively). The better mutation detection yield of sequencing from RNA was coupled with the superior prediction of clinical efficacy of first-line TKIs. In patients with acquired resistance, EGFR sequencing from RNA provided satisfactory detection of T790M (54.2%). These results demonstrated that EGFR sequencing using RNA as template greatly improves sensitivity for EGFR mutation detection from samples of MPE, highlighting RNA as the favourable source for analysing EGFR mutations from heterogeneous MPE specimens in NSCLC.

Multi-gene analyses from waste brushing specimens for patients with peripheral lung cancer receiving EBUS-assisted bronchoscopy.

OBJECTIVES Although flexible bronchoscopy with the assistance of miniature radial-probe endobronchial ultrasound (EBUS) is increasingly employed to diagnose peripheral lung cancer, transbronchial biopsies typically offer an insufficient amount of tissue to conduct additional molecular analysis. We evaluated the feasibility of multi-gene analyses from waste brushing samples obtained by EBUS-assisted bronchoscopy. MATERIALS AND METHODS For lung cancer patients with positive brushing cytology, analysis of EGFR, K-ras and EML4-ALK fusions were carried out, utilizing reverse transcription-polymerase chain reaction and Sanger sequencing on the cell-derived RNA retrieved from waste brushing samples. RESULTS EBUS-guided brushings were judged positive for tumor cells in 84 (68.9%) of the 122 patients with peripheral lung cancer receiving flexible bronchoscopy. Genotyping of EGFR and K-ras was successfully implemented in 80 (95.2%) of the 84 cytology-proven brushing samples, along with satisfactory yields to detect EGFR (55.0%) and K-ras (2.5%) mutations. The results of EGFR genotyping from the brushing specimens were highly concordant with those provided from other corresponding samples (concordance rate: 94%, kappa: 0.92). Of the 19 patients with adenocarcinoma or non-small cell lung cancer not otherwise specified harboring wild-type EGFR and K-ras, two cases (10.5%) were identified to harbor EML4-ALK fusions. CONCLUSION Our results suggest that multi-gene analyses from waste brushing specimens using RNA-based Sanger sequencing is highly feasible. This approach offers an opportunity to overcome the dilemma of flexible bronchoscopy in molecular diagnostics for lung cancer, and could potentially recruit more patients for targeted therapy according to the molecular characteristics of the tumor cells.

Effusion Immunocytochemistry as an Alternative Approach for the Selection of First-Line Targeted Therapy in Advanced Lung Adenocarcinoma

Introduction: Tumor tissue is often not obtainable or suitable for molecular-based epidermal growth factor receptor (EGFR) mutational analysis in advanced non–small-cell lung cancer (NSCLC). This retrospective and single-institution study was conducted to evaluate the role of effusion immunocytochemistry using two EGFR mutant-specific antibodies for the detection of relevant EGFR mutations in NSCLC, along with the selection of candidates for first-line therapy with EGFR tyrosine kinase inhibitors (TKIs). Methods: Immunocytochemistry using two antibodies binding specifically to the major forms of mutant EGFR, L858R, and E746-A750 deletion (delE746-A750), was performed on cell blocks of malignant pleural effusion (MPE) from 78 patients with lung adenocarcinoma, who received first-line EGFR TKIs. The yield of EGFR-mutation detection and prediction of response rate and progression-free survival to TKI treatment by immunocytochemistry were compared with those by clinical characteristics and EGFR sequencing using cell-derived RNA from MPEs. Results: Of the 78 MPE samples, direct sequencing using cell-derived RNA identified L858R mutation in 42 cases, deletions in exon 19 in 12 cases (delE746-A750 in eight cases), other types of mutations in three cases, and wild-type EGFR in 21 cases. Effusion immunocytochemistry with these two mutant-specific antibodies exhibited a sensitivity of 71% and 88% and a specificity of 86% and 96% for identifying predefined L858R and delE746-A750 mutations, respectively. Effusion immunocytochemistry provided a superior prediction of tumor response and progression-free survival to first-line EGFR TKIs than did clinical characteristics like sex and smoking status. Patients whose effusion immunocytochemistry showed a reaction to either of the two antibodies had a comparable TKI response rate (67% versus 72%) to those with EGFR mutations assessed by direct sequencing from cell-derived RNA. Conclusions: Effusion immunocytochemistry could be introduced into clinical practice to identify more NSCLC patients likely to have benefit from first-line TKI treatment, especially for those without adequate tissue for molecular-based EGFR analysis.

Clinical and prognostic implications of RET rearrangements in metastatic lung adenocarcinoma patients with malignant pleural effusion

OBJECTIVES RET rearrangements represent one of the newest molecular targets in non-small cell lung cancer (NSCLC). However, the prevalence, clinical characteristics, and outcome of patients with RET-rearranged lung adenocarcinoma in metastatic disease remain uncertain. MATERIALS AND METHODS Multiplex reverse transcription-polymerase chain reaction (RT-PCR) was used to detect KIF5B-RET and CCDC6-RET fusions from specimens of malignant pleural effusion (MPE) in patients with metastatic lung adenocarcinoma. The demographic data and outcome of patients with RET-rearranged tumors were compared with those with EGFR-mutant, KRAS-mutant, EML4-ALK-rearranged, and quadri-negative tumors. RESULTS Of the 722 patients with MPE of lung adenocarcinoma screened, 17 (2.4%) had RET-rearranged tumors. The detected RET rearrangements comprised 11 (65%) KIF5B-RET and 6 (35%) CCDC6-RET fusions, including 2 novel fusion variants identified. The presence of RET rearrangements was not associated with age at diagnosis, gender or smoking history, but predominantly seen in solid histological subtype. None of patients with RET-rearranged tumors had received kinase inhibitors with activity against RET kinase. The median overall survival was 22.4 months (95% CI, 8.8-36.0) for the 17 patients with RET-rearranged tumors, compared with 21.3 months (95% CI, 18.7-23.9; P=0.57) for the 451 patients with EGFR-mutant tumors, 5.4 months (95% CI, 2.7-8.1; P=0.002) for the 13 patients with KRAS-mutant tumors, 18.9 months (95% CI, 10.7-27.1; P=0.82) for the 51 patients with EML4-ALK-rearranged tumors, and 12.0 months (95% CI, 9.0-15.0; P=0.07) for the 190 patients with quadri-negative tumors. CONCLUSION Multiplex RT-PCR from specimens of MPE is feasible for the screening of RET rearrangements in NSCLC. Metastatic RET-rearranged lung adenocarcinoma patients with MPE might have favorable survival comparable to those with metastatic EGFR-mutant tumors.

Community-acquired thoracic empyema in older people

Objectives: To compare the clinical characteristics of community‐acquired thoracic empyema in older and younger patients and to analyze the effect of various factors on outcome.

Hypoglycemia associated with bacteremic pneumococcal infections

OBJECTIVES To evaluate the prevalence and associated presentations of hypoglycemia in bacteremic pneumococcal infections, and serotypes of the isolates. METHODS This was a retrospective study of 70 episodes of pneumococcal bacteremia that occurred in 2004 and 2005. RESULTS We found hypoglycemia (plasma glucose<3.05 mmol/l)) in six (8.6%) episodes. The patients were three children (mean age 3 years 1 month; range 1 year 5 months-4 years 5 months) and three adults (mean age 73.3 years; range 63-84 years). One child with asplenia and cyanotic heart disease had primary pneumococcal bacteremia. Of the other two children, one had meningitis and the other pneumonia. All the adults had cancer with previous chemotherapy and multilobar pneumonia, which progressed rapidly to respiratory failure. All patients developed their first hypoglycemic episode within two hours after presentation. The average plasma glucose during hypoglycemia was 1.78+/-0.78 mmol/l (range 0.33-2.94 mmol/l). One child and all of the adults died. Serotypes of isolates were those usually associated with severe pneumococcal infection: 6B and 19F in the children; 3, 14, and 23F in the adults. Only the asplenic child had received pneumococcal vaccine. CONCLUSIONS Hypoglycemia occurred in 8.6% of bacteremic pneumococcal infections and was associated with high mortality and serotypes that cause severe invasive disease. All patients suspected of having septicemia should have their glucose checked to avoid missing hypoglycemia leading to a worsening of their already poor condition.

Clinical Applications of Transthoracic Ultrasound in Chest Medicine

Transthoracic ultrasound (US) has become an important diagnostic tool in modern chest medicine. The range of thoracic lesions for which transthoracic US may yield useful diagnostic information has expanded to include not only chest wall and pleural lesions, but also peripheral lung nodules, pulmonary consolidations, necrotizing pneumonias and lung abscesses, tumors with obstructive pneumonitis, mediastinal masses, and peridiaphragmatic lesions. A variety of ultrasound features and signs of chest diseases have been well characterized and widely applied in clinical practice. US guidance increases the diagnostic success rate and decreases the complications associated with interventional procedures such as thoracentesis, closed tube drainage for pleural effusion, and needle biopsy of the pleura. Transthoracic needle aspiration or biopsy, under real-time US guidance, is a relatively safe and easy procedure, and may provide adequate tissue sampling of lesions for cytologic, histologic or microbiologic analysis. This article presents the general techniques and wide applications of transthoracic US and US-guided invasive procedures in the diagnosis and management of various chest diseases.