Efficacy of 3 fine-needle biopsy techniques for suspected pancreatic malignancies in the absence of an on-site cytopathologist.

BACKGROUND AND AIMS: EUS-guided fine-needle aspiration/biopsy (EUS-FNA/B) has a high diagnostic accuracy for pancreatic tumors. Most reports have focused on the diagnostic yield of cytology or histology; the ability of various FNA/B techniques to obtain an adequate mass of cells or tissue has rarely been investigated. METHODS: Patients with suspected pancreatic malignancy underwent EUS-FNB using a 22-gauge ProCore needle by either the stylet slow-pull-back technique (group A), conventional negative suction after stylet removal (group B), or non-suction after stylet removal (group C) in the absence of an on-site cytopathologist. The adequacy of the 3 techniques based on the diagnostic yield, cellularity, blood contamination, and core-tissue acquisition was evaluated. RESULTS: A total of 50 patients (27 males) were analyzed. The mean tumor size was 21 to 40 mm in 54%. The rate of a good or excellent proportion of cellularity was highest in group A compared with groups B and C (72% vs 60% vs 50%, P = .049). A >25% rate of blood contamination was more prevalent in group B (30% vs 42% vs 10%, P = .009). The rate of adequate core-tissue acquisition was not different (52% vs 34% vs 50%, P = .140). Based on the multivariate generalized estimation equation, the stylet slow-pull-back technique and a tumor size >40 mm were favorable factors for diagnostic adequacy. CONCLUSIONS: The stylet slow-pull-back technique might enable acquisition of tissue and assessment of cellularity for the diagnosis of pancreatic tumors suspected to be malignant. (Clinical trial registration number: KCT0002190.).

The Effect of Lifestyle Changes on Blood Pressure Control among Hypertensive Patients.

BACKGROUND: Hypertension is highly prevalent among patients who visit primary care clinics. Various factors and lifestyle behaviors are associated with effective blood pressure control. We aimed to identify factors and lifestyle modifications associated with blood pressure control among patients prescribed antihypertensive agents. METHODS: This survey was conducted at 15 hospital-based family practices in Korea from July 2008 to June 2010. We prospectively recruited and retrospectively assessed 1,453 patients prescribed candesartan. An initial evaluation of patients' lifestyles was performed using individual questions. Follow-up questionnaires were administered at 4, 8, and 12 weeks. We defined successful blood pressure control as blood pressure <140 mm Hg systolic and <90 mm Hg diastolic. RESULTS: Of the 1,453 patients, 1,139 patients with available data for initial and final blood pressures were included. In the univariate analysis of the change in performance index, weight gain (odds ratio [OR], 2.18; 95% confidence interval [CI], 1.52 to 3.11; P<0.001), physical inactivity (OR, 1.195; 95% CI, 1.175 to 3.387; P=0.011), and increased salt intake (OR, 1.461; 95% CI, 1.029 to 2.075; P=0.034) were related to inadequate blood pressure control. Salt intake also showed a significant association. Multivariate ORs were calculated for age, sex, body mass index, education, income, alcohol consumption, smoking status, salt intake, comorbidity, and family history of hypertension. In the multivariate analysis, sex (OR, 3.55; 95% CI, 2.02 to 6.26; P<0.001), salt intake (OR, 0.64; 95% CI 0.43 to 0.97; P=0.034), and comorbidity (OR, 1.82; 95% CI, 1.23 to 2.69; P=0.003) were associated with successful blood pressure control. CONCLUSION: Weight gain, physical inactivity, and high salt intake were associated with inadequate blood pressure control.

The association between a low urine pH and the components of metabolic syndrome in the Korean population: Findings based on the 2010 Korea National health and nutrition examination survey.

BACKGROUND: Low urine pH is related to obesity and insulin resistance, which are components of metabolic syndrome (MS). The aim of this study was to identify the relation between a low urine pH and MS after controlled for other covariates including demographic and lifestyle factors in adult Korean population. MATERIALS AND METHODS: We analyzed data from the 2010 Korea National Health and Nutrition Examination Survey, a cross-sectional and nationally representative survey and 1960 men and 2702 women were included in this study. Study subjects were divided into the group with urine pH <5.5 and the group with urine pH ≥5.5 refer to literature. We then evaluated the association between low urine pH and MS. RESULTS: After adjusting for age, sex, smoking status, drinking status, regular exercise, and blood urea nitrogen level, the odds ratio (OR) for the presence of MS in the group with urine pH <5.5 was 1.350 (95% confidence interval [95% CI]: 1.158-1.573) using the American Heart Association/National Heart, Lung, and Blood Institute criteria or 1.304 (95% CI: 1.082-1.572) using the International Diabetes Federation criteria. Among MS components, elevated fasting glucose (OR: 1.231, 95% CI: 1.058-1.433, P = 0.007) and elevated triglyceride (TG) (OR: 1.389, 95% CI: 1.189-1.623, P < 0.001) showed a significantly high OR. CONCLUSION: The findings confirmed that low urine pH is associated with MS in the Korean population. Among MS components, elevated fasting glucose and elevated TG showed a significantly high OR.

Factors Associated with Depressive Symptom in Chronic Obstructive Pulmonary Disease Based on the Third (2005) and Fourth (2008) Korea National Health and Nutritional Examination Survey (KNHANES III, IV).

BACKGROUND: Depressive symptoms accompanied by chronic obstructive pulmonary disease (COPD) can be influenced by socioeconomic status, associated chronic diseases and the current smoking status. This study was conducted to assess factors that are associated with depressive symptoms accompanied by COPD, using the data obtained from the Korea National Health and Nutritional Survey (KNHANES) conducted in 2005 and 2008. METHODS: From the third (2005) and the fourth (2008) KNHANES, 407 (0.9%) with physician-diagnosed COPD were selected. Of the 407 subjects, only 180 (0.4%) who reported having depressive symptoms were included in this study. The associations of depressive symptoms with socioeconomic status, associated chronic diseases and smoking status were investigated. RESULTS: Of the total 180 subjects, 45 (25%) had depressive symptoms. There were 102 males (55%) and 78 females (45%) with a slight predilection for males. In multivariate analysis, significant predictors of depressive symptoms were dependent activities of daily living (odds ratio [OR], 2.42; 95% confidence interval [CI], 2.06 to 2.84) and association with number of chronic diseases (OR of one, two, and three, 1.40, 1.72, 2.60; 95% CI of one, two, and three, 1.20 to 1.63,1.41 to 2.10,1.99 to 3.39). CONCLUSION: This study provides the basis for managing COPD patients in a clinical setting by understanding the number and characteristics of COPD patients with depressive symptoms. The results of this study suggest that primary physicians should manage COPD patients with consideration of risk factors for depressive symptom.

The use of PTC and RFA as treatment alternatives with low procedural morbidity in non-small cell lung cancer.

Minimally invasive percutaneous ablative therapies for treating lung cancers are currently being studied as treatment alternatives. This present study investigated the efficacies of percutaneous thoracic cryotherapy (PTC) and radiofrequency ablation (RFA) on clinical courses of pulmonary malignant tumours, especially in the setting of non-surgical candidates. Sixty-five patients with lung malignancy underwent sixty-seven sessions of RFA and nine sessions of PTC. We evaluated the results of RFA and PTC including efficacies, local progression rate, survival rate, and complications. Twenty-nine patients (43.3%) treated with RFA and six patients (66.7%) with PTC attained complete ablation. In small-sized lung mass (3 cm), complete ablation rate of RFA and PTC was increased to 76.2% and 85.7%, respectively. Additionally, we have found that the complete ablation group had significantly higher survival duration and progression free survival duration compared with the partial ablation group. Moreover, the complication profile was acceptable and the pain associated with the procedures disappeared within 1 day; 42 patients (62.7%) after RFA and all patients after PTC. This study provides evidence for the use of PTC and RFA as treatment alternatives with low procedural morbidity in the management of inoperable pulmonary malignant tumours, although the current study is limited by the small sample size and the short follow-up period.

Extra-axial chordoma presenting as a lung mass.

Chordomas are slow-growing, malignant tumors of bone that are thought to be derived from the primitive notochord and occur almost exclusively in the axial skeleton. The so-called extra-axial chordoma has been shown to demonstrate identical features to the classic chordoma, except that it is found outside the axial skeleton. Only six cases of extra-axial chordoma have been reported in the literature to date. In this report, we present another case of extra-axial chordoma for the first time originating from the lung parenchyma. A 79-year-old man presented a 7.3-cm-sized cavitary lung mass. Pathologic examination, including immunohistochemical studies, revealed that the mass was a chordoma. We report an extra-axial chordoma for the first time presenting as a lung mass.

Clinical significance of plasma and serum vascular endothelial growth factor in asthma.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a mediator of airway inflammation and remodeling in asthma. PURPOSE: We investigated whether VEGF levels are elevated in plasma and serum obtained from patients with asthma and evaluated whether levels of plasma VEGF correlated with those of serum VEGF. METHODS: We measured levels of plasma and serum VEGF in patients with stable asthma or with acute asthma and examined the correlation between plasma and serum VEGF concentration with initial forced expiratory volume in 1 second (FEV(1)). RESULTS: We found that levels of VEGF in plasma or in serum were significantly increased in stable asthmatic patients and even higher in acute asthmatic patients compared with the levels in healthy control subjects. The levels of serum VEGF correlated significantly with those of plasma VEGF. Additionally, the circulating VEGF levels were significantly inversely correlated with the percent predicted FEV(1). CONCLUSION: These results suggest that the overproduction of VEGF is implicated in asthma exacerbation and that measurement of either plasma or serum VEGF level can be a valid index in asthmatic patients. Therefore, the changes in the VEGF levels in peripheral blood of asthmatic patients can be used as a measure for progression of asthma during treatment.

Mast cells can mediate vascular permeability through regulation of the PI3K-HIF-1alpha-VEGF axis.

RATIONALE: Bronchial inflammation is usually accompanied by increased vascular permeability. Mast cells release a number of mediators that act directly on the vasculature, resulting in vasodilatation, increased permeability, and subsequent plasma protein extravasation. Vascular endothelial growth factor (VEGF) has been implicated to contribute to asthmatic tissue edema through its effect on vascular permeability. However, the effects of mast cells on VEGF-mediated signaling in allergic airway disease are not clearly understood. OBJECTIVES: An aim of the present study was to investigate the role of mast cells on VEGF-mediated signal transduction in allergic airway disease. METHODS: We used genetically mast cell-deficient WBB6F(1)-Kit(W)/Kit(W-v) (W/W(v)) mice and the congenic normal WBB6F(1)(+/+) mouse model for allergic airway disease to investigate the role of mast cells on VEGF-mediated signal transduction in allergic airway disease, more specifically in vascular permeability. MEASUREMENTS AND MAIN RESULTS: Our present study, with ovalbumin (OVA)-sensitized without adjuvant and OVA-challenged mice, revealed the following typical pathophysiologic features of allergic airway diseases: increased inflammatory cells of the airways, airway hyperresponsiveness, increased vascular permeability, and increased levels of VEGF. However, levels of VEGF and plasma exudation in W/W(v) mice after OVA inhalation were significantly lower than levels in WBB6F(1)(+/+) mice. Moreover, mast cell-reconstituted W/W(v) mice restored vascular permeability and VEGF levels similar to those of the WBB6F(1)(+/+) mice. Our data also showed that VEGF expression was regulated by hypoxia-inducible factor-1alpha (HIF-1alpha) activation through the phosphatidylinositol 3-kinase (PI3K)-HIF-1alpha pathway in allergic airway disease. CONCLUSIONS: These results suggest that mast cells modulate vascular permeability by the regulation of the PI3K-HIF-1alpha-VEGF axis.

Clear cell "sugar" tumor of the lung: a well-enhanced mass with an early washout pattern on dynamic contrast-enhanced computed tomography.

Clear cell tumor of the lung is a rare and very unusual benign pulmonary tumor. As clear cell tumor of the lung contains abundant cytoplasmic glycogen, this tumor is called "sugar tumor". We report a case of sugar tumor in a 64-yr-old man presenting as a round pulmonary nodule. On dynamic computed tomography (CT) scans, the solitary pulmonary nodule showed early wash-in enhancement with an early washout pattern like a lung malignancy. The patient underwent wedge resection for the tumor. Pathologic examination, including immunohistochemical studies, revealed that the nodule was a benign clear cell tumor, so-called "sugar tumor". Because only a small number of cases have been reported previously, clinical aspects, radiological characteristics on dynamic contrast-enhanced CT, and differential diagnosis of the tumor are not well established. Herein we present a clear cell tumor of the lung and discuss the clinical, radiological, and pathological features of the tumor.

Change of connexin 37 in allergen-induced airway inflammation.

Gap junction channels formed with connexins directly link to the cytoplasm of adjacent cells and have been implicated in intercellular signaling. Connexin 37 (Cx37) is expressed in the gas-exchange region of the lung. Recently, Cx37 has been reported to be involved in the pathogenesis of inflammatory disease. However, no data are available on the role of Cx37 in allergic airway inflammatory disease. In the present study, we used a murine model of ovalbumin (OVA)- induced allergic airway disease and primary murine epithelial cells to examine the change of Cx37 in allergic airway disease. These mice develop the following typical pathophysiological features of asthma: airway hyperresponsiveness, airway inflammation, and increased IL-4, IL-5, IL-13, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, eotaxin, and RANTES levels in lungs. Cx37 protein and mRNA expression were decreased in OVA-induced allergic airway disease. Immunoreactive Cx37 localized in epithelial layers around the bronchioles in control mice, which dramatically disappeared in allergen-induced asthmatic lungs. Moreover, the levels of Cx37 protein in lung tissues showed significantly negative correlations with airway inflammation, airway responsiveness, and levels of Th2 cytokines in lungs. These findings indicate that change of Cx37 may be associated with the asthma phenotype.

A novel thiol compound, N-acetylcysteine amide, attenuates allergic airway disease by regulating activation of NF-kappaB and hypoxia-inducible factor-1alpha.

Reactive oxygen species (ROS) play an important role in the pathogenesis of airway inflammation and hyperresponsiveness. Recent studies have demonstrated that antioxidants are able to reduce airway inflammation and hyperreactivity in animal models of allergic airway disease. A newly developed antioxidant, small molecular weight thiol compound, N-acetylcysteine amide (AD4) has been shown to increase cellular levels of glutathione and to attenuate oxidative stress related disorders such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. However, the effects of AD4 on allergic airway disease such as asthma are unknown. We used ovalbumin (OVA)-inhaled mice to evaluate the role of AD4 in allergic airway disease. In this study with OVA-inhaled mice, the increased ROS generation, the increased levels of Th2 cytokines and VEGF, the increased vascular permeability, the increased mucus production, and the increased airway resistance in the lungs were significantly reduced by the administration of AD4. We also found that the administration of AD4 decreased the increases of the NF-kappaB and hypoxia-inducible factor-1alpha (HIF-1alpha) levels in nuclear protein extracts of lung tissues after OVA inhalation. These results suggest that AD4 attenuates airway inflammation and hyperresponsiveness by regulating activation of NF-kappaB and HIF-1alpha as well as reducing ROS generation in allergic airway disease.

PTEN down-regulates IL-17 expression in a murine model of toluene diisocyanate-induced airway disease.

Toluene diisocyanate (TDI)-induced airway disease is a disorder characterized by chronic airway inflammation and airway remodeling. A recently discovered group of cytokines is the IL-17 family, which has been introduced as an important regulator of immune and inflammatory responses, including airway inflammation. Recently, we have reported that phosphatase and tensin homologue deleted on chromosome 10 (PTEN) plays a pivotal role in the pathogenesis of bronchial asthma. However, there are no available data for the effects of PTEN or IL-17 on TDI-induced airway disease and the relationship between PTEN and IL-17. We used a murine model to determine the role of PTEN in the pathogenesis of TDI-induced airway disease and the regulation of IL-17 production. These mice developed the typical pathophysiological features of TDI-induced airway disease and increased IL-17 expression in the lungs. Administration of phosphoinositide 3-kinase inhibitors or adenoviruses carrying PTEN cDNA (AdPTEN) reduced the pathophysiological features of TDI-induced airway disease and decreased the increased levels of IL-17 expression. Our results also showed that PI3K inhibitors or AdPTEN down-regulated a transcription factor, NF-kappaB activity, and BAY 11-7085 substantially reduced the increased levels of IL-17 after TDI inhalation. We also found that inhibition of IL-17 activity with an anti-IL-17 Ab reduced airway inflammation and airway hyperresponsiveness. These results suggest that PTEN plays a protective role in the pathogenesis of TDI-induced airway disease, at least in part through the regulation of IL-17 expression. Thus, PTEN may be a useful target for treating TDI-induced airway disease by modulating IL-17 expression.

Cysteinyl leukotriene upregulates IL-11 expression in allergic airway disease of mice.

BACKGROUND: Chronic airway inflammation and airway remodeling are important features of bronchial asthma. IL-11 is one of the important mediators involved in the process of airway inflammation and remodeling. Cysteinyl leukotrienes (cysLTs) play roles in recruitment of inflammatory cells, airway smooth muscle contraction, vascular leakage, increased mucus secretion, decreased mucociliary clearance, and airway fibrosis. OBJECTIVE: An aim of the present study was to determine the effect of the cysLTs on the regulation of IL-11 expression. METHODS: We used a C57BL/6 mouse model of allergic airway disease and murine tracheal epithelial cells to examine the effects of cysLTs on the regulation of IL-11 expression. RESULTS: Our present study with an ovalbumin-induced murine model of allergic airway disease revealed that levels of leukotriene C(4) (LTC(4)) in bronchoalveolar lavage fluids were increased and that administration of montelukast or pranlukast reduced the increased levels of LTC(4); the increased expression of IL-11 protein and mRNA in lung tissues; airway inflammation, bronchial hyperresponsiveness; the increased levels of TGF-beta(1), IL-4, and IL-13 in bronchoalveolar lavage fluids and lung tissues; and airway fibrosis. In addition, LTC(4) stimulates epithelial cells to produce IL-11. Our results also showed that cysLT type 1 receptor antagonists downregulated the activity of a transcription factor, nuclear factor kappaB, and BAY 11-7085 substantially reduced the increased levels of IL-11 after ovalbumin inhalation. CONCLUSION: These results suggest that cysLTs regulate the IL-11 expression in allergic airway disease. CLINICAL IMPLICATIONS: These findings provide one of the molecular mechanisms for the effects of cysLTs on airway inflammation and fibrosis in allergic airway diseases.

Antioxidant down-regulates interleukin-18 expression in asthma.

An alteration in the balance between a T-helper type 2 cell (Th2) response and a Th1 response may predispose to the development of bronchial asthma. Interleukin-18 (IL-18) has an ability to promote both Th1 and Th2 responses, depending on the surrounding cytokine environment. Reactive oxygen species (ROS) play a crucial role in the pathogenesis of airway inflammation and hyperresponsiveness. Recent studies have demonstrated that antioxidants are able to reduce airway inflammation and hyperreactivity in animal models of asthma. In this study, we used a C57BL/6 mouse model of allergic asthma to examine the effects of antioxidants on the regulation of IL-18 expression. Our present study with ovalbumin-induced murine model of asthma revealed that ROS production in cells from bronchoalveolar lavage fluids was increased and that administration of L-2-oxothiazolidine-4-carboxylic acid or alpha-lipoic acid reduced the increased levels of ROS, the increased expression of IL-18 protein and mRNA, airway inflammation, and bronchial hyperresponsiveness. Our results also showed that antioxidants down-regulated a transcription factor, nuclear factor-kappaB (NF-kappaB), activity. These results indicate that antioxidants may reduce IL-18 expression in asthma by inhibiting the activity of NF-kappaB and suggest that ROS regulate the IL-18 expression.