Polypoid Endobronchial Lung Cyst with Bronchoscopic Removal : A Case Report

Pulmonary bronchogenic cyst in adults is rare and the typical appearance is a sharply circumscribed, round or oval nodule or mass, usually in the medial third of the lungs. Bronchial polyps are rare histopathologically distinct nonneoplastic endobronchial lesions and are classified as multiple papillomas, solitary papillomas, and inflammatory polyps. We herein report a patient with polypoid endobronchial lung cyst. A 68-yr-old woman presented with a discomfort and pain in the right upper chest of four weeks??duration. Chest radiography revealed a cystic lesion in the right upper lung. Computed tomography revealed a 4×5 cm sized large cyst. Neither enlarged mediastinal lymph nodes nor extrabronchial involvements were observed. Flexible bronchoscopy revealed a peduncular polyp about 2 cm in length originating from the anterior segment of right upper lung. After bronchoscopic removal of polyp, cystic lesion of the right upper lung disappeared

TRAIL Enhances Apoptosis of Human Hepatocellular Carcinoma Cells Sensitized by Hepatitis C Virus Infection: Therapeutic Implications

Hepatitis C virus (HCV) infection causes chronic liver diseases leading to hepatocellular carcinoma (HCC) and liver failure. We have previously shown that HCV sensitizes hepatocytes to mitochondrial apoptosis via the TRAIL death receptors DR4 and DR5. Although TRAIL and its receptors are selective targets for cancer therapy, their potential against HCC with chronic HCV infection has not been explored yet. Here we show that HCV induces DR4/DR5-dependent activation of caspase-8 leading to elevation of apoptotic signaling in infected cells and also present TRAIL effect in HCV-induced apoptotic signaling. HCV induced proteolytic cleavage of caspase-9 by stimulating DR4 and DR5, resulting in subsequent cleavage of caspase-3. Further, HCV-induced proteolytic cleavage in caspase-8, caspase-9, and caspase-3 was enhanced in the presence of recombinant TRAIL. HCV-induced cleavage in caspase-9 and increase in caspase-3/7 activity was completely suppressed by silencing of either DR4 or DR5. Perturbing DR4/DR5-caspase-8 signaling complex by silencing DR4 and DR5 or by chemical inhibitor specific to caspase-8 led to decrease of HCV-induced cleavage of poly(ADP-ribose) polymerase (PARP), a substrate for caspase-3 during apoptosis, indicating the functional role of caspase-8 in HCV-induced apoptotic signaling network. Furthermore, TRAIL enhanced PARP cleavage in apoptotic response induced by HCV infection, indicating the effect of TRAIL for the induction of selective apoptosis of HCC cells infected with HCV. Given the importance of apoptosis in HCC development, our data suggest that HCV-induced DR4 and DR5 may be considered as an attractive target for TRAIL therapy against HCC with chronic HCV infection

Interleukin-13 and Its Receptors in Idiopathic Interstitial Pneumonia: Clinical Implications for Lung Function

Idiopathic interstitial pneumonia (IIP) is characterized by varying degrees of interstitial fibrosis. IL-13 and IL-4 are strong inducers of tissue fibrosis, whereas IFN-γ has antifibrotic potential. However, the roles of these substances in IIP remain unknown. IL-13, IL-4, and IFN-γ were measured in the BAL fluid of 16 idiopathic pulmonary fibrosis (IPF) patients, 10 nonspecific interstitial pneumonia (NSIP) patients, and 8 normal controls. The expression of IL-13 and IL-13Rα1/α2 in lung tissues was analyzed using ELISA and immunohistochemistry. IL-13 levels were significantly higher in IPF patients than the others (P<0.05). IL-4 levels were higher in both IPF and NSIP patients than in normal controls (P<0.05), and IFN-γ levels were lower in NSIP patients than in normal controls (P=0.047). IL-13 levels correlated inversely with FVC% (r=-0.47, P=0.043) and DLCO% (r=-0.58, P=0.014) in IPF and NSIP patients. IL-13 was strongly expressed in the smooth muscle, bronchial epithelium, alveolar macrophages and endothelium of IPF patients. IL-13Rα1, rather than IL-13Rα2, was strongly expressed in the smooth muscle, bronchial epithelium, and endothelium of IPF patients. IL-13 and its receptors may contribute to the pathogenesis of fibrosis in IIP and appear to be related to the severity of the disease

Current consensus and guidelines of contrast enhanced ultrasound for the characterization of focal liver lesions

The application of ultrasound contrast agents (UCAs) is considered essential when evaluating focal liver lesions (FLLs) using ultrasonography (US). Microbubble UCAs are easy to use and robust; their use poses no risk of nephrotoxicity and requires no ionizing radiation. The unique features of contrast enhanced US (CEUS) are not only noninvasiveness but also real-time assessing of liver perfusion throughout the vascular phases. The later feature has led to dramatic improvement in the diagnostic accuracy of US for detection and characterization of FLLs as well as the guidance to therapeutic procedures and evaluation of response to treatment. This article describes the current consensus and guidelines for the use of UCAs for the FLLs that are commonly encountered in US. After a brief description of the bases of different CEUS techniques, contrast-enhancement patterns of different types of benign and malignant FLLs and other clinical applications are described and discussed on the basis of our experience and the literature data

A reduced dose of ribavirin does not influence the virologic response during pegylated interferon alpha-2b and ribavirin combination therapy in patients with genotype 1 chronic hepatitis C

Background/AimsWhen combined with pegylated interferon alpha-2b (Peg-IFN α-2b) for the treatment of genotype 1 chronic hepatitis C (CHC) in Korea, the current guideline for the initial ribavirin (RBV) dose is based on body weight. However, since the mean body weight is lower for Korean patients than for patients in Western countries, current guidelines might result in Korean patients being overdosed with RBV.MethodsWe retrospectively reviewed the medical records of patients with genotype 1 CHC who were treated with Peg-IFN α-2b and RBV combination therapy. We divided the patients into groups A (≥15 mg/kg/day, n=23) and B (<15 mg/kg/day, n=26), given that the standard dose is 15 mg/kg/day. The clinical course in terms of the virologic response, adverse events, and dose modification rate was compared between the two groups after therapy completion.ResultsThe early response rates (92.0% vs. 83.3%, P=0.634) and sustained virologic response rates (82.6% vs. 73.1%, P=0.506) did not differ significantly between the two groups. During the treatment period, the RBV dose reduction rate was significantly higher in group A than in group B (60.9% vs. 23.1%, P=0.01).ConclusionsRBV dose reduction is performed frequently when patients are treated according to the current Korean guidelines. Given that lowering the RBV dose did not appear to decrease the virologic response during therapy, reducing RBV doses below the current Korean guideline may be effective for treatment, especially in low-weight patients

Predictive factors of contrast-enhanced ultrasonography for the response to transarterial chemoembolization in hepatocellular carcinoma

Background/AimsThe predictive role of contrast-enhanced ultrasonography (CEUS) before performing transarterial chemoembolization (TACE) has not been determined. We assessed the possible predictive factors of CEUS for the response to TACE.MethodsSeventeen patients with 18 hepatocellular carcinoma (HCC) underwent TACE. All of the tumors were studied with CEUS before TACE using a second-generation ultrasound contrast agent (SonoVue®, Bracco, Milan, Italy). The tumor response to TACE was classified with a score between 1 and 4 according to the remaining enhancing-tumor percentage based on modified response evaluation criteria in solid tumors (mRECIST): 1, enhancing tumor <25%; 2, 25%≤enhancing tumor<50%; 3, 50%≤enhancing tumor<75%; and 4, enhancing tumor≥75%). A score of 1 was defined as a "good response" to TACE. The predictive factors for the response to TACE were evaluated during CEUS based on the maximum tumor diameter, initial arterial enhancing time, arterial enhancing duration, intensity of arterial enhancement, presence of a hypoenhanced pattern, and the feeding artery to the tumor.ResultsThe median tumor size was 3.1 cm. The distribution of tumor response scores after TACE in all tumors was as follows: 1, n=11; 2, n=4; 3, n=2; and 4, n=1. Fifteen tumors showed feeding arteries. The presence of a feeding artery and the tumor size (≤5 cm) were the predictive factors for a good response (P=0.043 and P=0.047, respectively).ConclusionsThe presence of a feeding artery and a tumor size of less than 5 cm were the predictive factors for a good response of HCC to TACE on CEUS

Oncogenic CagA Promotes Gastric Cancer Risk via Activating ERK Signaling Pathways: A Nested Case-Control Study

Background: CagA cellular interaction via activation of the ERK signaling pathway may be a starting point in the development of gastric cancer. This study aimed to evaluate whether genes involved in ERK downstream signaling pathways activated by CagA are susceptible genetic markers for gastric cancer. Methods: In the discovery phase, a total of 580 SNPs within +/-5 kbp of 30 candidate genes were genotyped to examine an association with gastric cancer risk in the Korean Multi-center Cancer Cohort (100 incident gastric cancer case-control sets). The most significant SNPs (raw or permutated p value??0.02) identified in the discovery analysis were re-evaluated in the extension phase using unconditional logistic regression model (400 gastric cancer case-control sets). Combined analyses including pooled-and meta-analysis were conducted to summarize all the results. Results: 24 SNPs in eight genes (ERK, Dock180, C3G, Rap1, Src, CrkL, Mek and Crk) were significantly associated with gastric cancer risk in the individual SNP analyses in the discovery phase (p??0.05). In the extension analyses, ERK rs5999749, Dock180 rs4635002 and C3G rs7853122 showed marginally significant gene-dose effects for gastric cancer. Consistently, final combined analysis presented the SNPs as significantly associated with gastric cancer risk (OR = 1.56, [95% CI: 1.19-2.06], OR = 0.61, [95% CI: 0.43-0.87], OR = 0.59, [95% CI: 0.54-0.76], respectively). Conclusions: Our findings suggest that ERK rs5999749, Dock180 rs4635002 and C3G rs7853122 are genetic determinants in gastric carcinogenesis

Clinical features and outcomes of gastric variceal bleeding: retrospective Korean multicenter data

Background/AimsWhile gastric variceal bleeding (GVB) is not as prevalent as esophageal variceal bleeding, it is reportedly more serious, with high failure rates of the initial hemostasis (>30%), and has a worse prognosis than esophageal variceal bleeding. However, there is limited information regarding hemostasis and the prognosis for GVB. The aim of this study was to determine retrospectively the clinical outcomes of GVB in a multicenter study in Korea.MethodsThe data of 1,308 episodes of GVB (males:females=1062:246, age=55.0±11.0 years, mean±SD) were collected from 24 referral hospital centers in South Korea between March 2003 and December 2008. The rates of initial hemostasis failure, rebleeding, and mortality within 5 days and 6 weeks of the index bleed were evaluated.ResultsThe initial hemostasis failed in 6.1% of the patients, and this was associated with the Child-Pugh score [odds ratio (OR)=1.619; P<0.001] and the treatment modality: endoscopic variceal ligation, endoscopic variceal obturation, and balloon-occluded retrograde transvenous obliteration vs. endoscopic sclerotherapy, transjugular intrahepatic portosystemic shunt, and balloon tamponade (OR=0.221, P<0.001). Rebleeding developed in 11.5% of the patients, and was significantly associated with Child-Pugh score (OR=1.159, P<0.001) and treatment modality (OR=0.619, P=0.026). The GVB-associated mortality was 10.3%; mortality in these cases was associated with Child-Pugh score (OR=1.795, P<0.001) and the treatment modality for the initial hemostasis (OR=0.467, P=0.001).ConclusionsThe clinical outcome for GVB was better for the present cohort than in previous reports. Initial hemostasis failure, rebleeding, and mortality due to GVB were universally associated with the severity of liver cirrhosis

Genetic Susceptibility on CagA-Interacting Molecules and Gene-Environment Interaction with Phytoestrogens: A Putative Risk Factor for Gastric Cancer

OBJECTIVES: To evaluate whether genes that encode CagA-interacting molecules (SRC, PTPN11, CRK, CRKL, CSK, c-MET and GRB2) are associated with gastric cancer risk and whether an interaction between these genes and phytoestrogens modify gastric cancer risk. METHODS: In the discovery phase, 137 candidate SNPs in seven genes were analyzed in 76 incident gastric cancer cases and 322 matched controls from the Korean Multi-Center Cancer Cohort. Five significant SNPs in three genes (SRC, c-MET and CRK) were re-evaluated in 386 cases and 348 controls in the extension phase. Odds ratios (ORs) for gastric cancer risk were estimated adjusted for age, smoking, H. pylori seropositivity and CagA strain positivity. Summarized ORs in the total study population (462 cases and 670 controls) were presented using pooled- and meta-analysis. Plasma concentrations of phytoestrogens (genistein, daidzein, equol and enterolactone) were measured using the time-resolved fluoroimmunoassay. RESULTS: SRC rs6122566, rs6124914, c-MET rs41739, and CRK rs7208768 showed significant genetic effects for gastric cancer in both the pooled and meta-analysis without heterogeneity (pooled OR = 3.96 [95% CI 2.05-7.65], 1.24 [95% CI = 1.01-1.53], 1.19 [95% CI = 1.01-1.41], and 1.37 [95% CI = 1.15-1.62], respectively; meta OR = 4.59 [95% CI 2.74-7.70], 1.36 [95% CI = 1.09-1.70], 1.20 [95% CI = 1.00-1.44], and 1.32 [95% CI = 1.10-1.57], respectively). Risk allele of CRK rs7208768 had a significantly increased risk for gastric cancer at low phytoestrogen levels (p interaction<0.05). CONCLUSIONS: Our findings suggest that SRC, c-MET and CRK play a key role in gastric carcinogenesis by modulating CagA signal transductions and interaction between CRK gene and phytoestrogens modify gastric cancer risk