The usefulness of liquid-based cytology of bronchoalveolar lavage fluid combined with bronchial brush specimens in lung cancer diagnosis.

OBJECTIVE: To explore the diagnostic value of liquid-based cytology (LBC) of bronchoalveolar lavage fluid (BALF) combined with bronchial brushing (BB). METHODS: One hundred patients with pulmonary masses or nodules found by chest computed tomography (CT) or X-ray before bronchoscopy or other diagnostic biopsy examinations were selected consecutively for this retrospective study. BALF and BB were performed for all patients. After conventional smear via BB, we mixed the BALF and BB samples in a prepared thin-layer bottle. RESULTS: The sensitivity of LBC of BALF combined with BB was noticeably higher than that of BB alone in the total sample group (65.15% vs. 32.84%, respectively). Similarly, in both the bronchoscopically visible group and invisible group, a higher sensitivity for LBC of BALF with BB vs BB alone (68.89% vs. 39.13%, respectively; 57.14% vs. 19.05%, respectively) was observed. Additionally, the negative predictive value of LBC of BALF with BB was higher than that with BB alone (58.56% vs. 42.31%; 61.29% vs. 44.73%; 53.47% vs. 37.83%; total sample vs visible vs invisible groups, respectively). CONCLUSION: Regardless of whether lesions or nodules are bronchoscopically visible or invisible, LBC of BALF combined with BB may increase the diagnostic value over BB alone in lung cancer diagnosis.

Nasal Bacterial Microbiome Differs Between Healthy Controls and Those With Asthma and Allergic Rhinitis.

Perturbation of the microbiome has numerous associations with the phenotypes and progression in chronic airways disease. However, the differences in the nasal microbiome in asthma and allergic rhinitis (AR) have not been defined. We examined whether the nasal microbiome would vary among different comorbidities in asthma and AR and that those differences may be associated with the severity of asthma. Nasal lavage fluid was collected from 110 participants, including 20 healthy controls, 30 subjects with AR, 30 subjects with asthma and 30 subjects with combined asthma + AR. The Asthma Control Questionnaire (ACQ-7) was used to evaluate asthma control status. Using 16S rRNA bacterial gene sequencing, we analyzed nasal microbiome in patients with asthma, AR, combined asthma + AR, and healthy controls. Bacterial diversity was analyzed in corresponding with α diversity indices (Chao and Shannon index). Compared with healthy controls, the Chao index tended to be lower in subjects with AR (P = 0.001), asthma (P = 0.001), and combined asthma + AR (P = 0.001) when compared with healthy controls. Furthermore, the Shannon index was significantly lower in subjects with asthma (P = 0.013) and comorbid asthma with AR (P = 0.004) than the control subjects. Disparity in the structure and composition of nasal bacteria were also observed among the four groups. Furthermore, patients with combined asthma + AR and isolated asthma were divided into two groups according to the level of disease control: partially or well-controlled and uncontrolled asthma. The mean relative abundance observed in the groups mentioned the genera of Pseudoflavonifractor were dominated in patients with well and partially controlled disease, in both isolated asthma and combined asthma + AR. In subjects with uncontrolled asthma and combined asthma + AR, a lower evenness and richness (Shannon index, P = 0.040) was observed in nasal microbiome composition. Importantly, lower evenness and richness in the nasal microbiome may be associated with poor disease control in combined asthma + AR. This study showed the upper airway microbiome is associated with airway inflammation disorders and the level of asthma control.

A marked response to icotinib in a patient with large cell neuroendocrine carcinoma harboring an EGFR mutation: A case report.

The present study reports the case of an 84-year-old male with primary pulmonary large cell neuroendocrine carcinoma (LCNEC) harboring an epidermal growth factor receptor (EGFR) gene mutation that exhibited a long-lasting response to the EGFR-tyrosine kinase inhibitor (EGFR-TKI) icotinib. The patient had an extensive smoking history, a poor performance status, and presented with an irregular mass in the middle lobe of the right lung on computed tomography (CT) and an enlarged left supraclavicular lymph node on physical examination. Right middle lobe bronchial brushing during fiberoptic bronchoscopy identified poorly-differentiated cancer cells. The left supraclavicular lymph node was biopsied and a diagnosis of metastatic LCNEC was determined. Furthermore, an EGFR exon 19 deletion was identified by DNA sequencing. Following diagnosis, icotinib was administered at a dose of 125 mg three times a day. Chest CT scans were performed after 1 month of treatment, which indicated that the tumor was in partial remission. This marked response to icotinib lasted for 8 months. Thus, the present case illustrates the possibility of identifying EGFR mutations in LCNEC and indicates that EGFR-tyrosine kinase inhibitors may be an alternative treatment strategy for patients with LCNEC harboring activating EGFR mutations.

Evaluation of the factors affecting the maximum standardized uptake value of metastatic lymph nodes in different histological types of non-small cell lung cancer on PET-CT.

BACKGROUND: To evaluate the factors affecting the maximum standardized uptake value (SUVmax) of metastatic lymph nodes in different histological types of non-small cell lung cancer (NSCLC) on integrated positron emission tomography and computed tomography (PET-CT). METHODS: This was a retrospective, single-institution review of 122 patients with pathologically proven NSCLC who had PET-CT scanning at the same center. Lymph node metastases were pathologically confirmed in tissue specimens from surgical patients. Statistical evaluation of PET-CT results was performed on a per-nodal-station basis. RESULTS: The tumor SUVmax of squamous cell carcinoma (SCC) (11.0 ± 4.1) was higher than that of adenocarcinoma (AC) (7.4 ± 4.4) (P < 0.01), however, the SUVmax of the metastatic lymph nodes did not differ between the SCC (4.6 ± 3.1) and AC groups(3.6 ± 2.5) (P = 0.221). The SUVmax of metastatic lymph nodes was positively correlated with lymph node size but not with the primary tumor SUVmax, primary tumor size, tumor location and tumor differentiation. The frequency of a SUVmax of lymph nodes ≥2.5 was 44%, 80%,100% in SCC group and 39%, 59%, 90% in AC group when the short-axis diameter of metastatic lymph node was <10 mm, 10-15 mm, and > 15 mm, respectively. The low sensitivity for metastatic lymph nodes on PET-CT was increased when the SUVmax cut-off for malignancy was considered to be above the normal background compared with that when the SUVmax cut-off was above 2.5. CONCLUSIONS: There was no difference in the SUVmax of metastatic lymph nodes in the SCC and AC groups. The SUVmax of metastatic lymph nodes was positively correlated with metastatic lymph node size. There was a high false negative rate if lymph nodes with a short-axis diameter less than 10 mm and a extremely low false negative rate if lymph nodes with a short-axis diameter higher than 15 mm. Although an increased sensitivity may be achieved by decreasing the SUVmax cut-off, invasive staging may still be required for negative lymph nodes due to the lower sensitivity of PET-CT in both SCC and AC.

Relationship of redundant Th17 cells and IL-17A, but not IL-17 F, with the severity of obstructive sleep apnoea/hypopnoea syndrome (OSAHS).

BACKGROUND: The pathogenesis of obstructive sleep apnoea/hypopnoea syndrome (OSAHS), a highly prevalent disease, is not completely understood. The purpose of this study was to investigate the contributions of Th17 cells and the Th17-associated cytokines IL-17A and IL-17 F to OSAHS. METHODS: 46 male patients with a clinical suspicion of OSAHS were enrolled and divided into four groups based on their polysomnography results: controls and mild, moderate, and severe OSAHS. The serum levels of IL-17A and IL-17 F were determined by enzyme linked immunosorbent assay (ELISA), pulmonary arterial pressure (PAP) was determined by echocardiography, and Th17 cell frequencies in peripheral blood were measured by flow cytometry. RESULTS: Serum IL-17A levels in the severe group were elevated (median value: control group 0.89 pg/ml, mild OSAHS 1.02 pg/ml, moderate OSAHS 1.18 pg/ml, and severe OSAHS 1.62 pg/ml; p < 0.05) and positively correlated with AHI (r = 0.52, p < 0.05) but negatively related to the mean O2 saturation and lowest O2 saturation (r = -0.349, p < 0.05; and r = -0.336, p < 0.05, respectively). Although the frequencies of Th17 cells in the OSAHS groups were higher than that in the control group, these differences were not significant (p = 0.275). Pulmonary arterial hypertension was not present in our patients as the median PAP of the normal control and the mild, moderate, and severe OSAHS groups were 26, 27.5, 24.5, and 25.5 mmHg, respectively (p = 0.676). CONCLUSION: IL-17A may be involved in the pathogenesis of OSAHS and may represent a target for therapeutic intervention.

Clinical and radiographic characteristics of pulmonary nocardiosis: clues to earlier diagnosis.

BACKGROUND AND OBJECTIVES: Pulmonary nocardiosis (PN) is a rare but life-threatening disease that is caused by Nocardia spp. The aim of this study was to characterize the common risk factors, clinical features, imaging findings, treatment and outcomes of PN, which are useful for an early diagnosis and patient management. METHODS: From January 2009 to June 2013, a retrospective study was performed on all PN cases that were diagnosed at our hospital. RESULTS: The study included 17 patients who were diagnosed with PN. Of these patients, 4 developed concomitant disseminated disease. A male predominance was observed among the patients with PN (76.47%). The most common risk factors were corticosteroid therapy (64.71%), diabetes mellitus (29.41) and chronic lung disease (23.53%). Cough and fever were the most common symptoms (94% and 71%, respectively). One or more nodules or masses (82.35%) and consolidations (58.82%) were the most frequent radiologic abnormalities, and cavitation mostly occurred within two weeks. The median time to diagnosis was 25 days. Overall, the mortality rate was 18.75% for PN, and death was most frequent among patients who received immunosuppressive drugs. For the patients with central nervous system involvement, the mortality rate was 50%. CONCLUSION: PN remains a rare opportunistic infection that mainly affects immunocompromised patients. A high clinical index of suspicion is necessary for an early diagnosis and timely treatment in immunocompromised patients who present with new nodules or masses evolving into cavitation in a short amount of time.

Crizotinib overcomes hepatocyte growth factor-mediated resistance to gefitinib in EGFR-mutant non-small-cell lung cancer cells.

Acquired resistance develops ultimately in most non-small-cell lung cancer patients with epidermal growth factor receptor (EGFR) mutations who initially respond to EGFR tyrosine kinase inhibitors. Overexpression of hepatocyte growth factor (HGF) contributes to a considerable part of acquired resistance. Therefore, novel approaches are required for better management to overcome the resistance. Here, we tested whether crizotinib (PF02341066), a MET kinase inhibitor, can overcome two different HGF-triggered mechanisms of resistance to gefitinib in human EGFR mutant lung cancer cell lines HCC827 and PC-9. Compared with the monotherapy, the combined treatment of crizotinib and gefitinib induced apoptosis and significantly inhibited the growth of cells in the presence of HGF by blocking the MET/PI3K/Akt pathway. Further, we demonstrated that crizotinib plus gefitinib successfully prevented the emergence of gefitinib-resistant HCC827 cells induced by transient exposure to HGF. In vivo, the combination therapy with crizotinib and gefitinib also markedly suppressed the growth of gefitinib-resistant mouse xenografts established by injecting HCC827 cells mixed with HGF-producing fibroblasts (MRC-5 cells) subcutaneously into severe combined immunodeficient mice. In conclusion, these findings provided preclinical evidence that crizotinib can be used in the treatment of HGF-induced resistance to gefitinib in EGFR mutant lung cancer.