Chien-Hao Lie

Endobronchial Ultrasonography-Guided Transbronchial Needle Aspiration Increases the Diagnostic Yield of Peripheral Pulmonary Lesions: A Randomized Trial

BACKGROUND The diagnostic yield of endobronchial ultrasonography (EBUS)-guided transbronchial needle aspiration (TBNA) for peripheral pulmonary lesions (PPLs) has not been evaluated. The diagnostic impact of TBNA when the EBUS probe is adjacent to lesions remains to be determined. DESIGN A prospective, randomized trial. METHODS Two hundred two patients with PPLs and positive EBUS findings were enrolled. They were randomly classified into two groups. In the EBUS conventional diagnostic procedures (CDPs) group (103 patients), both transbronchial biopsy (TBB) and bronchial washing (BW) were performed. In the EBUS-TBNA plus CDPs group (99 patients), TBNA, TBB, and BW were performed. The diagnostic yield in each group was compared. RESULTS A total of 182 patients (94 in the EBUS CDPs group and 88 in the EBUS-TBNA plus CDPs group) were analyzed. The yield in the EBUS-TBNA plus CDPs group (78.4%) was significantly higher than the EBUS CDPs group (60.6%, p = 0.015). Cases in which the EBUS probe was located within the lesions had a significantly higher diagnostic yield (78.3%) than when the EBUS probe was adjacent to them (47.2%, p < 0.001). Concerning the three different techniques, TBNA showed the highest diagnostic yield (62.5%) in comparison to TBB (48.9%) and to BW (19.8%). The diagnostic yield of TBNA remained unchanged even when the EBUS probe was adjacent to the lesions (p = 0.89). No additional adverse effects were observed in the EBUS-TBNA plus CDPs group. CONCLUSIONS Applying TBNA to EBUS-guided CDPs further increased the diagnostic yield of PPLs without additional risk. The diagnostic advantage of TBNA became more obvious if the EBUS probe was adjacent to the lesions. TRIAL REGISTRATION Clinicaltrials.gov Identifier: NCT00626587.

Prognostic values of serum IP-10 and IL-17 in Patients with Pulmonary Tuberculosis

Objective: To identify patients at high risk of relapse after anti-tuberculosis (TB) therapy or with poor long-term outcomes. Methods: Fifty-one patients with pulmonary TB: 7 were classified as high association with both cavitations on initial chest radiography and positive sputum smear/cultures after two months of anti-TB treatment (HA group); 19 medium association (MA, one risk alone); and 25 low association (LA, neither risk). Serum interferon (IFN)-γ-inducible protein 10 (IP-10), interleukin-17 (IL-17), and C-reactive protein levels were investigated. Results: There was a trend towards higher serum IP-10 levels (p = 0.042) for HA patients throughout the 6-month treatment period. Month-2 IP-10 levels were higher in the HA than in the MA/LA group (656.2 ± 234.4 vs. 307.6 ± 258.5 pg/ml, adjusted p = 0.005). Receiver operating characteristic curves showed that the risk of relapse was well-captured by month-2 IP-10 levels at a cut-off value of 431 pg/ml (AUC=0.857, 95% CI 0.75–0.97, p = 0.003). Month-2 serum IL-17 levels were lower in non-survivors than survivors (15.7 ± 2.9 pg/ml vs. 24.6 ± 8.2 pg/ml, p = 0.001). Multivariate analysis demonstrated that a month-2 serum IL-17 level of ≤ 17 pg/ml (p = 0.026) was independently associated with all-cause mortality. Conclusions: Serum IP-10 and IL-17 levels after 2 months of anti-TB treatment may be biomarkers for estimating risk of both cavitation and delayed sputum conversion, and for predicting long-term mortality, respectively.

Peripheral Immune Cell Gene Expression Changes in Advanced Non-Small Cell Lung Cancer Patients Treated with First Line Combination Chemotherapy

Introduction Increasing evidence has shown that immune surveillance is compromised in a tumor-promoting microenvironment for patients with non-small cell lung cancer (NSCLC), and can be restored by appropriate chemotherapy. Methods To test this hypothesis, we analyzed microarray gene expression profiles of peripheral blood mononuclear cells from 30 patients with newly-diagnosed advanced stage NSCLC, and 20 age-, sex-, and co-morbidity-matched healthy controls. All the patients received a median of four courses of chemotherapy with cisplatin and gemcitabine for a 28-day cycle as first line treatment. Results Sixty-nine differentially expressed genes between the patients and controls, and 59 differentially expressed genes before and after chemotherapy were identified. The IL4 pathway was significantly enriched in both tumor progression and chemotherapy signatures. CXCR4 and IL2RG were down-regulated, while DOK2 and S100A15 were up-regulated in the patients, and expressions of all four genes were partially or totally reversed after chemotherapy. Real-time quantitative RT-PCR for the four up-regulated (S100A15, DOK2) and down-regulated (TLR7, TOP1MT) genes in the patients, and the six up-regulated (TLR7, CRISP3, TOP1MT) and down-regulated (S100A15, DOK2, IL2RG) genes after chemotherapy confirmed the validity of the microarray results. Further immunohistochemical analysis of the paraffin-embedded lung cancer tissues identified strong S100A15 nuclear staining not only in stage IV NSCLC as compared to stage IIIB NSCLC (p = 0.005), but also in patients with stable or progressive disease as compared to those with a partial response (p = 0.032). A high percentage of S100A15 nuclear stained cells (HR 1.028, p = 0.01) was the only independent factor associated with three-year overall mortality. Conclusions Our results suggest a potential role of the IL4 pathway in immune surveillance of advanced stage NSCLC, and immune potentiation of combination chemotherapy. S100A15 may serve as a potential biomarker for tumor staging, and a predictor of poor prognosis in NSCLC.

NEW IMAGE CHARACTERISTICS IN ENDOBRONCHIAL ULTRASONOGRAPHY FOR DIFFERENTIATING PERIPHERAL PULMONARY LESIONS

Endobronchial ultrasonography (EBUS) rapidly and accurately localizes peripheral pulmonary lesions. It can aid differential diagnosis by characterizing lesions and discriminating between neoplastic and non-neoplastic disease. From July 2005 through December 2006, patients with peripheral lesions underwent EBUS examination in a tertiary-referral teaching hospital. Image characteristics were subsequently correlated with definite histopathologic diagnosis. Three current-issued image patterns of EBUS were assayed from 40 initial patients, including (a) hypoechoic areas, (b) anechoic areas and (c) luminant areas around the probe. Excluding 22 cases because of inconsistent typing, 193 patients possessing definite diagnoses were enrolled in the investigation, of which 107 cases (55.4%) were neoplastic diseases. Hypoechoic areas appeared to be unrelated to the nature of the lesions (p = 0.288). Most lesions with anechoic areas were neoplasms (18 of 21 cases, 85.7%) and lesions without luminant areas suggested non-neoplastic disease (19 of 24 cases, 79.2%). Anechoic and luminant areas were significantly different between neoplasm and non-neoplasm groups (p = 0.003 and p < 0.001, respectively). The average additional time for EBUS required was 3.85 +/- 2.36 min (range 1 to 13 min). In conclusion, this uncomplicated and time-saving method of using EBUS image patterns could provide additional information to facilitate differential diagnoses.

First- or Second-line Gefitinib Therapy in Unknown Epidermal Growth Factor Receptor Mutants of Non-Small-Cell Lung Cancer Patients Treated in Taiwan

Gefitinib is effective in treating patients with non-small-cell lung cancer (NSCLC). The response rate and improvement in survival are related to several aspects, including race, gender, smoking status, and histology; however, little is known about the relationship between survival and length of gefitinib treatment. We conducted this retrospective study to examine this relationship and identify the predictive factors influencing survival and tumor response in chemonaive and chemotherapy patients who had stage IIIb or IV NSCLC with unknown epidermal growth factor receptor mutants. This analysis was aimed to clarify the difference between first- and second-line gefitinib therapy. Among the 918 newly diagnosed, inoperable NSCLC patients from March 2003 to December 2006, 437 (47.6%) had ever received gefitinib therapy. One hundred forty-nine patients (34.0%) who selected gefitinib as first- or second-line therapy were included in the analysis. The overall survival rates of first- and second-line gefitinib therapy were 12.8 months and 20.7 months, respectively (P = .110). The shorter overall survival may be caused by the omission of platinum-based doublet chemotherapy in 37 patients from the first-line group (39.4%). There was also no significant difference in progression-free survival (6.8 months versus 4.9 months; P = .415), and the objective tumor response and disease control rates were similar. Better prognosis and tumor response was associated with female gender, adenocarcinoma, nonsmokers, and good performance status. The difference in overall survival between patients undergoing second-line treatment compared with those undergoing first-line treatment preceding chemotherapy was significant (P = .041). The overall survival, progression-free survival, and tumor response rates were similar in the patients who received gefitinib as initial therapy or after conventional chemotherapy.

Blood absolute T cell counts may predict 2-month treatment response in patients with pulmonary tuberculosis.

Background and objective: Little is known about the usefulness of lymphocyte subsets as early predictors of anti-tuberculosis (TB) treatment response in immuno-competent patients. Methods:Among a total of 64 patients with culture positive pulmonary TB, 29 remained sputum smear/culture positive or had delayed resolution on CXR (slow responders (SR)), and 35 had sputum culture conversion to negative and rapid resolution on CXR (fast responders (FR)) after two months of anti-tuberculosis treatment. Clinical parameters and lymphocyte subsets were investigated. Results: A larger proportion of patients in the SR group had cavities on CXR, bilateral lung involvement, positive acid-fast bacilli stains, and complaint of cough at diagnosis than those in the FR group. Absolute counts of CD3+ T cells (p = 0.016) and CD8+ T cells (p = 0.012) at diagnosis were both significantly higher in the SR group. This trend was present throughout the 6-month treatment course. Absolute T cell counts (odds ratio (OR) 1.002, 95% confidence interval (CI) 1.0–1.004), positive sputum acid fast bacilli stain (OR 6.69, 95% CI 1.37–32.77) and bilateral lung involvemment on CXR (OR 13.114, 95% CI 1.87–92.14) at diagnosis were independent predictors for a slow response. Combining these three predictors, a prediction score (PS) could be calculated to display an optimal discrimination for slow response (area under the curve (AUC) = 0.855, p < 0.001) whereas absolute T cell counts yielded the highest discriminative value on an individual level (AUC = 0.676, p = 0.015). Conclusions: A higher T cell count at diagnosis in patients with TB may predict a slow response to two months of treatment. The calculation of a PS further increased predictive accuracy and performance.

Pulmonary Granulomatous Inflammation and Unexplained Repeated Infections-A Case of Chronic Granulomatous Disease

Chronic granulomatous disease (CGD) is a rare inherited disorder caused by a failure of intracellular superoxide production by phagocytes. It is usually identified in early childhood with severe recurrent bacterial and fungal infections. We present a case of CGD in a young male adult in whom the disease initially presented with left middle lung consolidation with cavitation. The patient had a history of unexplained repeated infection (including liver abscess and submandibular cellulitis at the age of 17 and 19 years). A specimen of cutting biopsy of the lung showed granulomatous inflammation. Pulmonary granuloma is a common manifestation of tuberculosis in Taiwan, but no acid-fast bacilli were identified by Ziehl-Neelsen staining in a specimen of sputum and cutting biopsy. In addition, no autoimmune disease was detected. The patient had negative respiratory burst activity in the polymorphonuclear leukocyte function test, a low response in the chemiluminescence test, and a normal finding in the chemotaxis assay, so the diagnosis of CGD was finally established. CGD rarely starts presenting in adulthood, either because it is not well-recognized in non-pediatric chest wards or because of the administration of potent antimicrobials that unintentionally treat many CGD-associated infections, postponing the diagnosis until more severe infections occur. Therefore, any adolescent or adult with unexplained and repeated infections that are accompanied by granuloma formation should be checked for phagocyte function defects. Early diagnosis of CGD is important because of the benefits of timely treatment and infection prophylaxis.

Primary Endobronchial Minute Leiomyoma-A Case Report

Primary endobronchial minute leiomyoma is a rare benign tumor of the lung. In this report, we discuss a case of this rare tumor in a 78-year-old male who presented with hemoptysis and was diagnosed as endobronchial leiomyoma based on the histopathological examination of a bronchial biopsy from the posterior segmental bronchus of the left upper lobe. Bronchofiberscopy revealed a polypoid tumor (0.1×0.1 cm) in the posterior segmental bronchus of the left upper lobe, which was easily extirpated by transbronchial forceps biopsy. We could not find another primary lesion or metastases in any other organ. Following treatment, this patient has been asymptomatic with no recurrence of haemoptysis.

Pulmonary Dysfunction and Microangiopathic Hemolytic Anemia as the Primary Presentation of Gastric Cancer: A Case Report

Microangiopathic hemolytic anemia (MAHA) is a rare complication of disseminated carcinoma. It usually occurs at the late or terminal stage of cancer. Only a few cases with MAHA as an initial presentation have been reported in the literature. We describe herein a case of gastric adenocarcinoma complicated with lymphangitic carcinomatosis on the chest roentgenogram, along with intractable anemia. This 33-year-old man had complained of prolonged cough and breathlessness for 1 month. Physical examination revealed anemia and jaundice. The peripheral blood smear disclosed many schistocytes and thrombocytopenia. After a careful work-up, adenocarcinoma of a gastric origin was diagnosed. It is suggested that in patients with bilateral pulmonary infiltrates and microangiopathic hemolytic anemia, the diagnosis of gastric cancer should be considered.