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BACKGROUND: Systemic inflammation response is a crucial prognostic factor for various cancers. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are two inflammation-based prognostic scores. The significance of preoperative NLR and PLR in patients with esophageal squamous cell carcinoma (ESCC) receiving curative esophagectomy remains largely undefined. Hence, this study aimed to evaluate the significance of preoperative NLR and PLR in patients with ESCC receiving curative esophagectomy in southern Taiwan. METHODS: A consecutive group of 107 patients with ESCC undergoing esophagectomy between January 2001 and December 2012 were retrospectively reviewed. The NLR and PLR of these 107 patients were calculated and correlated with clinicopathological parameters, overall survival (OS), and disease-free survival (DFS). RESULTS: NLR ≥2.5 was significantly correlated with higher T classification (P=0.006) and advanced clinical AJCC 7(th) stage (P=0.047). PLR ≥150 was significantly associated with higher T classification (P=0.009). Univariate survival analysis showed that NLR ≥2.5 and PLR ≥150 were associated with poor OS (P=0.009 and P=0.007, respectively) and poor DFS (P=0.006 and P=0.005, respectively). On multivariate comparison, PLR ≥150 was independently associated with poor OS [P=0.001, hazard ratio (HR): 2.475] and poor DFS (P

Esophageal squamous cell carcinoma (ESCC) and head/neck squamous cell carcinoma (HNSCC) are very common cancers worldwide, and there is higher incidence of synchronous ESCC/NSCC in Taiwan. The aim of the current study was to investigate the efficacy of different chemotherapy regimens in patients with locally advanced synchronous ESCC/HNSCC who received curative concurrent chemoradiotheapy (CCRT). A total of 75 patients were identified and assigned to one of two groups: 45 patients receiving cisplatin/5-fluorouracil (5-FU) regime in one group and 30 patients receiving a weekly cisplatin regime in the other. Overall survival (OS) was calculated from the date of diagnosis of the ESCC or HNSCC to the date of death from any cause or the most recent follow-up. Kaplan&ndash, Meier curves and log-rank tests were used to estimate OS and differences between the two groups, respectively. There was no significant difference in the analysis of OS between the cisplatin/5-FU and the weekly cisplatin groups. However, patients that interrupted their CCRT were found to have worse OS compared to those without interruptions (5.4 months versus 18.8 months, p = 0.002). In subgroup analysis, patients without interruptions of CCRT had a better OS than those with interruptions in the cisplatin/5-FU group (13.0 months versus 5.4 months, p = 0.041) as well as in the weekly cisplatin group (21.4 months versus 5.0 months, p = 0.017). Interruption of CCRT was the only independently poor prognostic factor of OS in the univariate and multivariate (hazard ratio 0.18, p &lt, 0.001) analyses. Most interruption of CCRT resulted from adverse events (AEs) or serious AEs. Although there was no significant difference in the incidence of AEs between these two groups, lower incidence of adverse events was mentioned in the weekly cisplatin group. Our study suggests that interruption of CCRT is an independently poor prognostic factor of OS, and that completion of CCRT without interruption is more important than the choice of chemotherapeutic regimen for patients with synchronous ESCC/HNSCC.

BACKGROUND This study aimed to determine clinical outcomes using various drugs during tuberculosis (TB) treatment among living donor liver transplant (LDLT) recipients with TB and to assess the impact of performing LDLT in patients with active TB at the time of LDLT. MATERIAL AND METHODS Out of 1313 LDLT performed from June 1994 to May 2016, 26 (2%) adult patients diagnosed with active TB were included in this study. Active TB was diagnosed using either TB culture, PCR, and/or tissue biopsy. RESULTS The median age was 56 years and the male/female ratio was 1.6: 1. Most patients had pulmonary TB (69.2%), followed by extrapulmonary and disseminated TB (15.4% each). Fourteen (53.8%) patients underwent LDLT even with the presence of active TB. All patients concurrently received anti-TB [Rifampicin-based: 13 (50%); Rifabutin-based: 12 (46.2%); INH-based: 1 (3.8%)] and immunosuppressive drugs [Tacrolimus-based: 6 (23%); Sirolimus/Everolimus-based: 20 (77%)]. During treatment, adverse drug reactions (ADR) occurred in 34.6% of patients: acute rejection in 6 (23.1%), hepatotoxicity in 2 (7.7%), and blurred vision in 1 (3.8%). Twenty-three (88%) patients completed their TB treatment. Neither TB recurrence nor TB-specific mortality were observed. Three (11.5%) patients died of non-TB-related causes. The overall 5-year survival rate was 86.2%. Patients with ADRs had a higher incidence of incomplete TB treatment (log-rank: p=0.012). Furthermore, patients with incomplete treatment were significantly associated with decreased overall survival (log-rank: p

Background: Programmed cell death-ligand 1 (PD-L1) is present in a subgroup of cancer patients who may be favorable targets for immune checkpoint inhibitor therapies. However, the significance of the PD-L1 expression in esophageal squamous cell carcinoma (ESCC) patients receiving neoadjuvant chemoradiotherapy remains unclear. Methods: By means of PD-L1 immunohistochemistry 22C3 pharmDx assay, we evaluate the PD-L1 expression and its association with clinical outcome in 107 ESCC patients receiving neoadjuvant chemoradiotherapy. Results: Patients with positive PD-L1 expression have significantly lower pathological complete response rates (13% versus 32%, P = 0.036) than those with negative PD-L1 expression. Univariate survival analysis found that positive PD-L1 expression were correlated with poor overall survival (P = 0.004) and inferior disease-free survival (P &lt, 0.001). In a multivariate analysis, positive PD-L1 expression was independently associated with the absence of a pathologically complete response (P = 0.044, hazard ratio: 3.542), worse overall survival (P = 0.006, hazard ratio: 2.017), and inferior disease-free survival (P &lt, 0.001, hazard ratio: 2.516). Conclusions: For patients with ESCC receiving neoadjuvant chemoradiotherapy, positive PD-L1 expression independently predicts the poor chemoradiotherapy response and worse treatment outcome. Thus, our data suggests that PD-L1 may be an influential biomarker for prognostic classification and for immune checkpoint inhibitor therapies in ESCC patients receiving neoadjuvant chemoradiotherapy.

Background Sirtuin 1 (SIRT1) regulates DNA repair and metabolism by deacetylating target proteins. SIRT1 may be oncogenic because its overexpression has been detected in many cancers. The aim of the present study was to clarify the prognostic role of SIRT1 in patients with esophageal squamous cell carcinoma (ESCC) and evaluate the effect of SIRT1 inhibitor in vitro. Methods The expression of SIRT1 was evaluated immunohistochemically in 155 surgically resected ESCC and the staining results were evaluated semiquantitatively by the Immunoreactive Scoring System. The clinical features and treatment outcome were analyzed. The effect of SIRT1 inhibitor, SIRT 1 inhibitor IV, (S)-35, was investigated in vitro on ESCC cell lines. Results The expression of SIRT1 on ESCC did not correlate with age, gender, tumor location, stage, T classification, N classification, surgical margin or histology. Univariate analysis showed that SIRT1 overexpression was associated with inferior overall survival (P = 0.004) and disease-free survival (P = 0.004). In multivariate comparison, SIRT1 overexpression remained independently associated with worse overall survival (P = 0.009, hazard ratio = 1.776) and disease-free survival (P = 0.017, hazard ratio = 1.642). In cell lines, SIRT1 inhibitor inhibited ESCC growth. Conclusions Our study suggests that SIRT1 overexpression is an independent prognosticator for patients with ESCC and the SIRT1 inhibitor suppressed cell proliferation of ESCC cell lines. Our findings suggest that inhibition of SIRT1 signaling may be a promising novel target for ESCC.

// Yen-Hao Chen 1, 2, 3 , Hung-I Lu 4 , Yu-Ming Wang 5 , Chien-Ming Lo 4 , Shang-Yu Chou 5 , Cheng-Hua Huang 1 , Li-Hsueh Shih 6 , Su-Wei Chen 7 and Shau-Hsuan Li 1 1 Department of Hematology-Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 2 Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan 3 School of Medicine, Chung Shan Medical University, Taichung, Taiwan 4 Department of Thoracic & Cardiovascular Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 5 Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 6 Department of Nursing, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan 7 Department of Anesthesia, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan Correspondence to: Shau-Hsuan Li, email: lee.a0928@msa.hinet.net Keywords: celiac lymph node; esophageal cancer; squamous cell carcinoma; concurrent chemoradiotherapy Received: June 20, 2017 Accepted: September 23, 2017 Published: October 16, 2017 ABSTRACT Background: To evaluate the clinical outcomes of celiac lymph node (LN) metastasis in patients with locally advanced esophageal squamous cell carcinoma (ESCC) receiving curative concurrent chemoradiotherapy (CCRT). Materials and Methods: A total of 375 stage III ESCC patients were identified, including 51 patients with celiac LN metastasis and 324 patients without celiac LN metastasis. Among these 324 patients without celiac LN metastasis, 51 were matched with the 51 patients with celiac LN metastasis using the propensity score matching method. Results: Overall, the celiac LN metastasis group had worse progression-free survival (PFS) and overall survival (OS) than the non-celiac LN metastasis group and the matched non-celiac LN metastasis group. For the ESCC patients with celiac LN metastasis, lower third ESCC was significantly associated with superior PFS and OS. For patients with upper/middle third ESCC, the celiac LN metastasis group had worse PFS and OS than the non-celiac LN metastasis group and the matched non-celiac LN metastasis group. For patients with lower third ESCC, there were no significant differences in PFS and OS between these groups. Conclusions: Our study suggests celiac LN metastasis is a poor prognostic factor for locally advanced ESCC patients receiving curative CCRT. Among these ESCC patients with celiac LN metastasis, tumor location is a strongly prognostic factor, indicating patients with lower third ESCC have better PFS and OS than those with upper/middle third ESCC. The 6 th American Joint Committee on Cancer staging system seems more favorable than 7 th edition in the definition of celiac LNs for those patients.

// Chih-Hung Chen 1 , Yung-Lung Chen 2 , Pei-Hsun Sung 2 , Cheuk-Kwan Sun 3 , Kuan-Hung Chen 4 , Yi-Ling Chen 2 , Tien-Hung Huang 2 , Hung-I Lu 5 , Fan-Yen Lee 5 , Jiunn-Jye Sheu 5 , Sheng-Ying Chung 2 , Mel S. Lee 6, * and Hon-Kan Yip 2, 7, 8, 9, 10, * 1 Divisions of General Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 2 Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 3 Department of Emergency Medicine, E-Da Hospital, I-Shou University School of Medicine for International Students, Kaohsiung, Taiwan 4 Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 5 Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 6 Department of Orthopedics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 7 Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan 8 Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan 9 Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan 10 Department of Nursing, Asia University, Taichung, Taiwan * Both authors contributed equally to this work Correspondence to: Hon-Kan Yip, email: han.gung@msa.hinet.net Mel S. Lee, email: mellee@cgmh.org.tw Keywords: acute respiratory distress syndrome, sepsis, inflammation, adipose-derived mesenchymal stem cell, platelets Received: October 11, 2016 Accepted: March 06, 2017 Published: July 17, 2017 ABSTRACT This study assessed whether combining adipose-derived mesenchymal stem cells (ADMSC) with preactivated, disaggregated shape-changed platelets (PreD-SCP) was superior to either therapy alone for protecting rat lung from acute respiratory distress syndrome (ARDS) complicated by sepsis. ARDS and sepsis were induced through 100% oxygen inhalation and peritoneal administration of 1.5 mg/kg lipopolysaccharide (LPS), respectively. Adult-male Sprague-Dawley rats (n=40) were randomized into sham-control (SC), ARDS-LPS, ARDS-LPS-ADMSC (1.2x10 6 cells), ARDS-LPS-PreD-SCP (3.0x10 8 , intravenous administration), and ARDS-LPS-ADMS/PreD-SCP groups, and were sacrificed 72 h after 48 h ARDS induction. Lung injury scores (LIS) and collagen deposition were highest in ARDS-LPS, lowest in SC, higher in ARDS-LPS+ADMSC than in ARDS-LPS+PreD-SCP and ARDS-LPS+ADMS/PreD-SCP, and higher in ARDS-LPS+PreD-SCP than in ARDS-LPS+ADMS/PreD-SCP (all p

// Fan-Yen Lee 1, * , Kuan-Hung Chen 2, * , Christopher Glenn Wallace 3 , Pei-Hsun Sung 4 , Jiunn-Jye Sheu 1 , Sheng-Ying Chung 4 , Yung-Lung Chen 4 , Hung-I Lu 1 , Sheung-Fat Ko 5 , Cheuk-Kwan Sun 6 , Hsin-Ju Chiang 7 , Hsueh-Wen Chang 8 , Mel S. Lee 9, ** and Hon-Kan Yip 4, 10, 11, 12, 13, ** 1 Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 2 Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 3 Department of Plastic Surgery, Royal Devon & Exeter Hospital, Exeter, United Kingdom 4 Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 5 Department of Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 6 Department of Emergency Medicine, E-Da Hospital, I-Shou University School of Medicine for International Students, Kaohsiung, Taiwan 7 Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 8 Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan 9 Department of Orthopedics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 10 Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 11 Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 12 Department of Nursing, Asia University, Taichung, Taiwan 13 Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan * These authors have contributed equally to this work ** These authors have contributed equally to this work senior co-authors Correspondence to: Hon-Kan Yip, email: han.gung@msa.hinet.net Keywords: acute respiratory distress syndrome, sepsis syndrome, inflammatory and immune reactions, xenogeneic mesenchymal stem cell, mortality Received: January 10, 2017 Accepted: April 03, 2017 Published: April 21, 2017 ABSTRACT This study tested the hypothesis that xenogeneic human umbilical cord-derived mesenchymal stem cell (HUCDMSC) therapy would improve survival rates in rats with acute respiratory distress-syndrome (ARDS, induction by 48 h inhalation of 100% oxygen) and sepsis-syndrome (SS, induction by cecal-ligation and puncture) (ARDS-SS). Adult-male Sprague-Dawley rats were categorized into group 1 (sham-controls), group 2 (ARDS-SS), group 3 [ARDS-SS+HUCDMSC (1.2 ×10 6 cells administered 1 h after SS-induction)], and group 4 [ARDS-SS+HUCDMSC (1.2 ×10 6 cells administered 24 h after SS-induction)]. The mortality rate was higher in groups 2 and 4 than in groups 1 and 3 (all p

This study investigated the clinical outcome of locally advanced cervical esophageal squamous cell carcinoma (ESCC) patients who received curative concurrent chemoradiotherapy (CCRT) and their differences from thoracic ESCC patients. Among 411 enrolled ESCC patients, including 63 with cervical and 348 with thoracic ESCC, 63 thoracic patients were propensity score-matched to the 63 cervical patients. For cervical ESCC, T4b and high tumor grade were independent prognostic factors of a worse overall survival (OS) in univariate and multivariate analyses. The response rates to curative CCRT between cervical and the matched thoracic ESCC groups were similar but cervical ESCC had a better OS than that of the matched thoracic group (21.4 versus 10.1 months, p = 0.012). Better OS was mentioned to be in the patients with complete response (CR), whether in the cervical or matched thoracic ESCC group. For patients without CR, patients who underwent esophagectomy had superior OS than those without operation in the matched thoracic ESCC group (11.6 versus 11.9 months, p = 0.73). Only three patients received operation in the cervical ESCC group, thus the survival difference was not significant. Curative CCRT may be a reasonable treatment for cervical ESCC in clinical practice, and the role of surgery should be considered as salvage therapy if residual disease is evident.

ObjectivesPost-chemoradiotherapy (CRT) FDG PET is a useful prognosticator of esophageal cancer. However, debate on the diverse criteria of previous publications preclude worldwide multicenter comparisons, and even a universal practice guide. We aimed to validate a simple qualitative interpretation criterion of post-CRT FDG PET for outcome stratification and compare it with other criteria.MethodsThe post-CRT FDG PET of 114 patients with esophageal squamous cell carcinoma (ESCC) were independently interpreted using a qualitative 4-point scale (Qual4PS) that identified focal esophageal FDG uptake greater than liver uptake as residual tumor. Cohen's κ coefficient (κ) was used to measure interobserver agreement of Qual4PS. The Kaplan-Meier method and Cox proportional hazards regression analyses were used for survival analysis. Other criteria included a different qualitative approach (QualBK), maximal standardized uptake values (SUVmax3.4, SUVmax2.5), relative change of SUVmax between pre- and post-CRT FDG PET (ΔSUVmax), mean standardized uptake values (SUVmean), metabolic volume (MV) and total lesion glycolysis (TLG).ResultsOverall interobserver agreement on the Qual4PS criterion was excellent (κ: 0.95). Except the QualBK, SUVmax2.5, and TLG, all the other criteria were significant predictors for overall survival (OS). Multivariable analysis showed only Qual4PS (HR: 15.41; P = 0.005) and AJCC stage (HR: 2.47; P = 0.007) were significant independent variables. The 2-year OS rates of Qual4PS(‒) patients undergoing CRT alone (68.4%) and patients undergoing trimodality therapy (62.5%) were not significant different, but the 2-year OS rates of Qual4PS(+) patients undergoing CRT alone (10.0%) were significantly lower than in patients undergoing trimodality therapy (42.1%).ConclusionsThe Qual4PS criterion is reproducible for assessing the response of ESCC to CRT, and valuable for predicting survival. It may add value to response-adapted treatment for ESCC patients, and help to decide whether surgery is warranted after CRT.

Background ESPN (Espin), an actin filament-binding protein, plays an important role in regulating the organization, dimensions, dynamics, and signaling capacities of the actin filament-rich, microvillus-type specializations that mediate sensory transduction in various mechanosensory and chemosensory cells. Recent few studies show that ESPN regulates metastasis and cell proliferation in melanoma. However, the significance of ESPN in other cancers such as esophageal squamous cell carcinoma (ESCC) remains largely unknown. Methods Immunohistochemistry was performed in 169 patients with ESCC and correlated with clinicopathological features and survival. The functional role of ESPN in ESCC cells was determined by ESPN-mediated siRNA. Results Univariate analyses showed that high ESPN expression was associated with inferior overall survival (P = 0.005) and disease-free survival (P = 0.035). High ESPN expression was an independent prognosticator in multivariate analysis for overall survival (P = 0.009, hazard ratio = 1.688) and disease-free survival (P = 0.049, hazard ratio = 1.451). The 5-year overall survival rates were 30% and 54% in patients with high and low expression of ESPN, respectively. Inhibition of endogenous ESPN in ESCC cells decreased ESCC growth by reducing cell proliferating rates. Conclusions High ESPN expression is independently associated with poor prognosis in patients with ESCC and downregulation of ESPN inhibits ESCC cell growth. Our results suggest that ESPN may be a novel therapeutic target for patients with ESCC.

Endothelial cell (EC) dysfunction plays a crucial role for arterial obstructive disease. This study tested the therapeutic role of autologous endothelial progenitor cells (EPCs)/rosuvastatin-(Rosu)/valsartan-(Val) on repair of injured carotid ECs. Male Sprague-Dawley rats (n = 60) were categorized into five groups [sham-control (SC), left common carotid artery injury induced by balloon denudation (LCA(BD)), LCA(BD) + Rosu (10 mg/kg/day), LCA(BD) + Val (20 mg/kg/day), and LCA(BD) + EPC (1.2 × 10(6))]. By day 5, the LCA was harvested from each rat (n = 6/each time interval in group) after the procedure. Carotid-ring angiogenesis was significantly lower in LCA(BD) than the other groups (all P < 0.001). Compared with LCA(BD), the number of EC was significantly higher in LCA(BD) treated with adipose-derived mesenchymal stem cells (ADMSCs) and more significantly higher in LCA(BD) treated with EPCs (all P < 0.001). Gene expression of EC (CD31/vWF), EPC (SDF-1α/CXCR4) and angiogenesis (VEGF/VEGF-receptor/angiopoietin/eNOS) and EC intercellular junction (VE-cadherin) biomarkers were significantly lower in LCA(BD) than in groups LCA(BD) + Rosu to LCA(BD) + EPC (all P < 0.001). Conversely, the gene expression of inflammatory (VCAM-1/MMP-9/TNF-α), oxidative-stress (NOX-1/NOX-2), apoptosis (cleaved caspase-3/PARP) and thrombin cofactor (thrombomodulin) biomarkers were significantly higher in LCA(BD) than in other groups (all P < 0.001). By day 14, the neointimal-layer area and cellular expressions of (CD40+/CD68+) were highest in LCA(BD), lowest in SC, significantly higher in LCA(BD) + Val than in LCA(BD) + Rosu and LCA(BD) + EPC (all P < 0.001). In conclusion, EPCs were comparable to rosuvastatin and valsartan in upregulation of angiogenesis and repair of injured carotid ECs.

We investigated the cardioprotective effect of melatonin (Mel) and exendin-4 (Ex4) treatment in a rat model of cardiorenal syndrome (CRS). Male-adult SD rats (n=48) were randomly and equally divided into sham-control (SC), dilated cardiomyopathy (DCM) (doxorubicin 7 mg/kg i.p. every five days/ 4 doses), CRS (defined as DCM + CKD) only, CRS-Mel (20 mg/kg/day), CRS-Ex4 (10 μg/kg/day) and CRS-Mel-Ex4. In-vitro results showed protein expressions of oxidative-stress (NOX-1/NOX-2/oxidized protein), DNA/mitochondrial-damaged (γ-H2AX/cytosolic cytochrome-C) and apoptotic (cleaved caspase-3/PARP) biomarkers, and senescence (β-galactosidase cells) were upregulated, whereas mitochondrial ATP level was decreased in doxorubicin/ p-Cresol-treated H9C2 cells that were revised by Mel and Ex4 treatments (all p

Antioxidant peptide SS-31 is a class of cell-permeable small peptides, which selectively resides on the inner mitochondrial membrane and possesses intrinsic mitochondrial protective capacities. In this study we investigated the therapeutic effects of antioxidant peptide SS-31 on transverse aortic constriction (TAC)-induced pulmonary arterial hypertension (PAH) in a murine model.Adult male mice were divided into 3 groups: sham-operated mice, TAC mice, and TAC+SS-31 mice that underwent TAC surgery and received SS-31 (2 mg/d, ip) for 60 d. The right ventricular systolic blood pressure (RVSBP) was measured on d 60 prior to sacrificing the mice; then their right heart and lung tissues were collected for histological and biochemical examinations. Lung injury scores were defined by the increased crowded area and decreased number of alveolar sacs.TAC mice showed significantly higher RVSBP compared with sham-operated mice, the elevation was substantially suppressed in TAC+SS-31 mice. The same pattern of changes was found in pulmonary levels of oxidative stress proteins (NOX-1/NOX-2/oxidized proteins), cytosolic cytochrome c, biomarkers related to inflammation (MMP-9/TNF-α/iNOS), calcium overload index (TRPC1, 2, 4, 6), apoptosis (mitochondrial BAX, cleaved caspase 3/PARP), fibrosis (Smad3/TGF-β), hypoxic (HIF-1α), DNA damage (γ-H2AX) and endothelial function (eNOS/ET-1R), as well as in lung injury score, number of muscularized vessels in lungs, number of TRPC1(+) and HIF-1α(+) cells in pulmonary artery, and number of γ-H2AX(+) and Ki-67(+) cells in lung parenchyma. An opposite pattern of changes was observed in pulmonary anti-fibrotic markers (Smad1/5, BMP-2), number of small vessels, and number of alveolar sacs. In contrast, the levels of antioxidant proteins (HO-1/NQO-1/GR/GPx) in lung parenchyma were progressively and significantly increased from sham-operated mice, TAC mice to TAC+SS-31 mice.Antioxidant peptide SS-31 administration effectively attenuates TAC-induced PAH in mice.

Effects of cyclic deformation and annealing treatment on conductive durability of indium tin oxide (ITO) thin film deposited on polyethylene terephthalate (PET) substrate are investigated. In-situ electrical and mechanical tests of ITO/PET sheet under various combinations of cyclic and static loadings are conducted at room temperature. Experimental results show that the number of cycles to failure is significantly decreased with an increase in displacement amplitude, given a specific extent of electrical resistance change of ITO/PET sheet. A static holding period of 1000 s in various loading modes plays a role in influencing the failure of ITO/PET sheet. Cyclic bending combined with a static tensile holding generally generates more damages and a smaller number of cycles to failure than does that combined with a compressive holding, neutral holding, or no holding. Under a small fatigue loading, the conductive durability of ITO/PET sheet is increased with an increase in annealing temperature. However, there is little effect of annealing temperature on ITO/PET fatigue life under a larger displacement amplitude of fatigue loading. Using a surface-based cohesive modeling technique, a simplified three-dimensional finite element analysis micromodel subjected to tensile and compressive loadings is numerically analyzed to clarify the failure mechanism of interfacial and buckling-like delamination which governs the change in electrical conductivity of ITO/PET sheet. Modeling results indicate that buckle height of the ITO/PET micromodel subjected to tensile loading is significantly greater than that of compressive loading, providing more evidence of the aforementioned effect of loading mode.

Stromal cell-derived factor-1&alpha, (SDF-1&alpha, ) is a chemokine that has been reported to be involved in tumor progression in several malignancies. This study aimed to evaluate the crucial role of SDF-1&alpha, in patients with esophageal squamous cell carcinoma (ESCC) who underwent esophagectomy. A total of 169 patients with ESCC were identified, including overexpression of SDF-1&alpha, in 60 patients and low expression of SDF-1&alpha, in 109 patients by immunohistochemical analysis. Two ESCC cell lines, TE1 and KYSE30, were selected to evaluate the tumor cell proliferative effect of SDF-1&alpha, Univariate and multivariate analyses showed that high tumor (T) status, positive lymph node metastasis, tumors located in the upper esophagus, and SDF-1&alpha, overexpression were significantly related to worse disease-free survival and overall survival. In addition, the two cell lines were treated with SDF-1&alpha, AMD3100 (an SDF-1&alpha, ligand receptor antagonist), and chemotherapeutic agents (cisplatin). Our in vitro study results showed that SDF-1&alpha, promoted the proliferation of tumor cells, and blocking the SDF-1&alpha, pathway displayed a growth inhibition effect in a dose-dependent manner. SDF-1&alpha, plays an important role in the progression of ESCC and is an independent prognostic factor for ESCC patients who underwent esophagectomy.

Background: Definite chemoradiotherapy (dCRT) followed by surgery is a treatment option for clinical T4b esophageal squamous cell carcinoma (ESCC). However, the feasibility and safety of salvage esophagectomy for clinical T4b patients after dCRT remains unclear. This study aimed to analyze the outcomes and prognostic factors of salvage esophagectomy for cT4b ESCC after dCRT. Materials and Methods: From 2008 to 2017, a total of 21 patients who underwent salvage esophagectomy after dCRT for initially unresectable disease at the author's institution were assessed. The study retrospectively reviewed the baseline characteristics of these cases and evaluated the prognostic factors and surgical outcomes. Results: Among the study group, R0 resection was achieved in 9 patients (43%). The rate of major complications classified as Clavien-Dindo classification (CDc) Grade IIIb or higher was 24.0%. The overall survival (OS) and disease-free survival (DFS) rates were 46% and 25% at 3 years, respectively. Univariate analysis showed that the patients who had R0 resection had a significantly better OS (P = 0.012, 78% vs. 25%) and DFS (P = 0.025, 39% vs. 18%) compared to those with R1/2 resection. The patients with minor complications (CDc ≤ IIIa) had a better OS (P = 0.002, 61% vs. 0%) compared to the group with major complications (CDc ≥ IIIb). The pathological results with earlier T (ypT0-2) were better than with advanced T (ypT3-4) for 3-year OS (P = 0.042, 83% vs. 30%) and 3-year DFS (P = 0.018, 53% vs. 13%). In multivariate analysis, R0 resection (P = 0.042, 95% confidence interval [CI] 1.051–15.617) and CDc ≤ IIIa (P = 0.019, 95% CI 1.286–16.023) were associated with a significantly better prognosis with regards to 3-year OS, and R0 resection was associated with a significantly better prognosis with regards to 3-year DFS (P = 0.0339, 95% CI 1.108–13.136). Conclusion: The results showed that in salvage esophagectomy for T4b ESCC patients after dCRT, R0 resection and CDc ≤ IIIa were favorable prognostic factors. The surgical complications were still high, but this was acceptable in view of the potential long-term survival after salvage esophagectomy. Carefully selecting candidates remains an important issue before surgery.

Background To evaluate the role of blood vascular endothelial growth factor (VEGF) kinetics in patients with locally advanced esophageal squamous cell carcinoma (ESCC) receiving curative concurrent chemoradiotherapy (CCRT). Methods A total of 97 locally advanced ESCC patients were enrolled. All the patients had their blood drawn at three time points to determine their levels of VEGF, including pre-chemotherapy (day 0), post-chemotherapy (day 5), and pre-cycle 2 chemotherapy (day 28). The VEGF levels were evaluated according to the day 0 value, day 5 value, day 28 value, day 5/day 0 ratio, day 28/day 0 ratio, and day 28/day 5 ratio. A VEGF cut-off level of 80 pg/mL was applied. Results In the analysis of progression-free survival (PFS), the patients less than 60 years old had significantly superior PFS compared to those more than 60 years old. Patients who had VEGF 80 pg/mL and a day 28/day 5 ratio > 1, respectively. In the analysis of overall survival (OS), patients with N0–1 status had significantly superior OS compared to those with N2–3 status. Furthermore, patients who had VEGF 80 pg/mL, a day 5/day 0 ratio > 1, and a day 28/day 5 ratio > 1, respectively. In the multivariate analysis, only VEGF

Over the past few decades, there was an encouraging breakthrough in bridging the gap between advancements in the evolution of diagnosis and treatment towards a better outcome in achalasia. The purpose of this review is to provide updated knowledge on how the current evidence has bridged the gap between advancements in the evolution of diagnosis and treatment of esophageal achalasia. The advent of high-resolution manometry and standardization based on the Chicago classification has increased early recognition of the disease. These 3 clinical subtypes of achalasia can predict the outcomes of patients, and the introduction of POEM has revolutionized the choice of treatment. Previous evidence has shown that laparoscopic Heller myotomy (LHM) and anterior fundoplication were considered the most durable treatments for achalasia. Based on the current evidence, POEM has been evolving as a promising strategy and is effective against all 3 types of achalasia, but the efficacy of POEM is based on short- and medium-term outcome studies from a limited number of centers. Types I and II achalasia respond well to POEM, LHM, and PD, while most studies have shown that type III achalasia responds better to POEM than to LHM and PD. In general, among the 3 subtypes of achalasia, type II achalasia has the most favorable outcomes after medical or surgical therapies. The long-term efficacy of POEM is still unknown. The novel ENDOFLIP measures the changes in intraoperative esophagogastric junction dispensability, which enables a quantitative assessment of luminal patency and sphincter distension; however, this technology is in its infancy with little data to date supporting its intraoperative use. In the future, identifying immunomodulatory drugs and the advent of stem cell therapeutic treatments, including theoretically transplanting neuronal stem cells, may achieve a functional cure. In summary,it is important to identify the clinical subtype of achalasia to initiate target therapy for these patients.

IntroductionThe present study investigated the crucial role of inflammation-based prognostic scores in locally advanced cervical esophageal squamous cell carcinoma (ESCC) patients who underwent curative concurrent chemoradiotherapy (CCRT).MethodsThere were 411 ESCC patients enrolled, including 63 cervical ESCC patients. Using the propensity score matching method, 63 thoracic ESCC patients were matched to the 63 cervical ESCC patients. The inflammation-based prognostic scores included the neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), albumin level, c-reactive protein (CRP) level, modified Glasgow prognostic score (mGPS), and CRP/albumin ratio. The chi-square test and Kaplan–Meier method were used for categorical variable data and overall survival, respectively. A Cox regression model was performed for univariate and multivariable analyses.ResultsWith respect to cervical ESCC, NLR ≥ 2.5 (P = 0.019), PLR ≥ 103 (P = 0.013), CRP value >10 mg/l (P = 0.040), mGPS ≥ 1 (P = 0.040), and CRP/albumin ratio ≥ 9.5 (P = 0.033) were significant predictors of worse overall survival (OS) in the univariate analysis. In a multivariable analysis, PLR ≥ 103 (P = 0.010, HR: 2.66, 95% CI [1.27–5.58]) and mGPS ≥ 1 (P = 0.030, HR: 2.03, 95% CI [1.07–3.86]) were the independent prognostic parameters of worse OS. The prognostic value of these biomarkers in the matched thoracic ESCC patients was similar and compatible with the results in the cervical ESCC group in the univariate and multivariable analyses.ConclusionsOur study suggests that these inflammation-based prognostic scores are helpful in clinical practice, and PLR and mGPS may predict the prognosis for locally advanced cervical ESCC patients who receive curative CCRT.

This study tested the hypothesis that entresto therapy effectively protected heart and lung against cardiopulmonary syndrome (CPS) caused by transverse aortic constriction (TAC) in rat. Adult-Male SD rats (n = 36) were equally categorized into group 1 [sham-operated control (SC)], group 2 [SC + enalapril (7 mg/kg/day) since day-28 after TAC induction], group 3 [SC + entresto (30 mg/kg/day) since day-14 after TAC induction], group 4 (TAC only), group 5 (TAC + enalapril) and group 6 (TAC + entresto) and euthanized at day 60 after TAC induction. By day 60, the left-ventricular (LV) ejection fraction was significantly lower in group 4 than in other groups and significantly lower in groups 5 and 6 than in groups 1 to 3, whereas the ratios of heart and lung weights to tibial-length as well as the right-ventricular-systolic blood pressure exhibited an opposite pattern among the groups (all P

Background. The osteopontin has been involved in therapeutic resistance in a variety of cancers. But, the significance of osteopontin expression on the prognosis of patients with locally advanced esophageal squamous cell carcinoma (ESCC) receiving chemoradiotherapy is unclear.Methods.In 80 patients with locally advanced ESCC receiving preoperative chemoradiotherapy between 1999 and 2012, osteopontin expression was evaluated by immunohistochemistry and correlated with treatment outcome. The functional role of osteopontin in ESCC cell lines was determined by osteopontin-mediated siRNA.Results. Osteopontin expression and clinical T4 classification were significantly associated with poor pathological complete response. Univariate analyses demonstrated that osteopontin overexpression and clinical T classification, T4, were significantly associated with worse overall survival and disease-free survival. In multivariate comparison, osteopontin overexpression and clinical T classification, T4, represented the independent adverse prognosticator. In ESCC cell lines, endogenous osteopontin depletion by osteopontin-mediated siRNA increased sensitivity to cisplatin. Osteopontin expression is independently correlated with the response of chemoradiotherapy and prognosis of patients with locally advanced ESCC receiving preoperative chemoradiotherapy.Conclusions. Our results suggest that osteopontin may be a potential therapeutic target for patients with ESCC treated with preoperative chemoradiotherapy.

This study tested the hypothesis that shock wave therapy (SW) enhances mitochondrial uptake into the lung epithelial and parenchymal cells to attenuate lung injury from acute respiratory distress syndrome (ARDS). ARDS was induced in rats through continuous inhalation of 100% oxygen for 48 h, while SW entailed application 0.15 mJ/mm2for 200 impulses at 6 Hz per left/right lung field. In vitro and ex vivo studies showed that SW enhances mitochondrial uptake into lung epithelial and parenchyma cells (allp<0.001). Flow cytometry demonstrated that albumin levels and numbers of inflammatory cells (Ly6G+/CD14+/CD68+/CD11b/c+) in bronchoalveolar lavage fluid were the highest in untreated ARDS, were progressively reduced across SW, Mito, and SW + Mito (allp<0.0001), and were the lowest in sham controls. The same profile was also seen for fibrosis/collagen deposition, levels of biomarkers of oxidative stress (NOX-1/NOX-2/oxidized protein), inflammation (MMP-9/TNF-α/NF-κB/IL-1β/ICAM-1), apoptosis (cleaved caspase 3/PARP), fibrosis (Smad3/TGF-β), mitochondrial damage (cytosolic cytochrome c) (allp<0.0001), and DNA damage (γ-H2AX+), and numbers of parenchymal inflammatory cells (CD11+/CD14+/CD40L+/F4/80+) (p<0.0001). These results suggest that SW-assisted Mito therapy effectively protects the lung parenchyma from ARDS-induced injury.

Despite high in-hospital mortality associated with acute respiratory distress syndrome (ARDS), there is no effective therapeutic strategy. We tested the hypothesis that combined melatonin-mitochondria treatment ameliorates 100% oxygen-induced ARDS in rats. Adult male Sprague-Dawley rats (n = 40) were equally categorized into normal controls, ARDS, ARDS-melatonin, ARDS with intravenous liver-derived mitochondria (1500 μg per rat 6 hr after ARDS induction), and ARDS receiving combined melatonin-mitochondria. The results showed that 22 hr after ARDS induction, oxygen saturation (saO2 ) was lowest in the ARDS group and highest in normal controls, significantly lower in ARDS-melatonin and ARDS-mitochondria than in combined melatonin-mitochondria group, and significantly lower in ARDS-mitochondria than in ARDS-melatonin group. Conversely, right ventricular systolic blood pressure and lung weight showed an opposite pattern compared with saO2 among all groups (all P < 0.001). Histological integrity of alveolar sacs showed a pattern identical to saO2 , whereas lung crowding score exhibited an opposite pattern (all P < 0.001). Albumin level and inflammatory cells (MPO+, CD40+, CD11b/c+) from bronchoalveolar lavage fluid showed a pattern opposite to saO2 (all P < 0.001). Protein expression of indices of inflammation (MMP-9, TNF-α, NF-κB), oxidative stress (oxidized protein, NO-1, NOX-2, NOX-4), apoptosis (mitochondrial Bax, cleaved caspase-3, and PARP), fibrosis (Smad3, TGF-β), mitochondrial damage (cytochrome C), and DNA damage (γ-H2AX+) exhibited an opposite pattern compared to saO2 in all groups, whereas protein (HO-1, NQO-1, GR, GPx) and cellular (HO-1+) expressions of antioxidants exhibited a progressively increased pattern from normal controls to ARDS combined melatonin-mitochondria group (all P < 0.001). In conclusion, combined melatonin-mitochondrial was superior to either treatment alone in attenuating ARDS in this rat model.

Benign metastasizing leiomyoma (BML) is a rare cause of pulmonary nodules that occurs when uterine leiomyomas metastasize to the lung. The management of these lesions varies from resection and hysterectomy to nonsurgical treatments such as hormonal therapy. Herein we report a 60-year-old patient with diffuse variant size lung nodules mimicing metastatic pulmonary malignancy.

Background To evaluate the clinical significance of supraclavicular lymph node (SCLN) in patients with locally advanced esophageal squamous cell carcinoma (ESCC) receiving curative concurrent chemoradiotherapy (CCRT). Materials and methods We retrospectively analyzed all 369 locally advanced ESCC patients treated with CCRT between 2000 and 2015, including 70 patients with SCLN metastasis and 299 patients without SCLN metastasis. Results For these locally advanced ESCC patients treated with curative CCRT, N0-2 were significantly associated with superior progression-free survival (PFS) and overall survival (OS) in univariate and multivariable analyses. However, there were no significant differences in PFS and OS between the SCLN metastasis and non-SCLN metastasis groups; a subgroup analysis also revealed there was no significant differences in PFS and OS between patients with and without SCLN metastasis either in the N0-2 or in the N3 subgroup analysis. Conclusions Our study suggests that SCLN metastasis is not a prognostic factor in locally advanced ESCC patients receiving curative CCRT, and that SCLNs should be considered to be regional LNs and treated with curative intent.

This study tested the hypothesis that SS31 therapy could effectively protect the heart against transverse aortic constriction (TAC)-induced hypertrophic cardiomyopathy (HCM) damage. Adult-male B6 mice (n=36) were equally divided into sham-operated control (group 1), TAC only (group 2) and TAC+SS31 (group) (2.0 mg/kg/day by intra-peritoneal administration from day 28 after TAC induction) and euthanized by day 60. In vitro results showed that SS31 markedly suppressed angiotensin-II induced protein expressions of BNP/β-MHC, ATM, p-P38 and P53 and ATP damage in H9C2 cells, and protein expression of pro-collagen-I/CTGF in fibroblasts (all P

Background The Jumonji-domain containing 3 has diverse roles in multiple cancers. Here, we investigated its prognostic significance in esophageal squamous cell carcinoma. Methods By using immunohistochemistry, the Jumonji-domain containing 3 expression was examined in 109 surgically resected esophageal squamous cell carcinomas and correlated with treatment outcome. The functional role of Jumonji-domain containing 3 in esophageal squamous cell carcinoma cells was determined by Jumonji-domain containing 3–mediated small interfering ribonucleic acid. Results Univariate analysis showed that Jumonji-domain containing 3 overexpression was associated with inferior overall survival (P = .004) and disease-free survival (P = .002). In a multivariate comparison, Jumonji-domain containing 3 overexpression remained independently associated with worse overall survival (P = .017, hazard ratio = 1.898) and disease-free survival (P = .011, hazard ratio = 1.901). The 5-year overall and disease-free survival rates were 66% and 58% in patients with a low expression of Jumonji-domain containing 3 and 34% and 27% in patients with overexpression of Jumonji-domain containing 3. Silencing Jumonji-domain containing 3 in esophageal squamous cell carcinoma cells inhibited cell growth rate and bromodeoxyuridine incorporation ability. In contrast, a gain of function of Jumonji-domain containing 3 promoted esophageal squamous cell carcinoma cell proliferation. Furthermore, Jumonji-domain containing 3 expression contributes to Ras/MEK pathway. Conclusion Jumonji-domain containing 3 overexpression was independently associated with poor prognosis in patients with esophageal squamous cell carcinoma. In vitro, Jumonji-domain containing 3 expression regulated esophageal squamous cell carcinoma cell growth. These results may further elucidate the role of Jumonji-domain containing 3 in esophageal squamous cell carcinoma and provide a potential new therapeutic approach for patients with esophageal squamous cell carcinoma.

OBJECTIVE:Areca nut chewing is carcinogenic to humans. However, little is known about the impact of areca nut chewing on esophageal squamous cell carcinoma (ESCC). METHODS:We retrospectively reviewed 286 ESCC patients who received surgery or preoperative chemoradiotherapy followed by surgery at our institution. Background characteristics including areca nut chewing history were analyzed. The 4-nitroquinoline 1-oxide (4-NQO)-induced murine ESCC model was used to test the impact of arecoline, a main constituent of areca nut, on ESCC. RESULTS:Compared to patients without areca nut chewing history, patients with areca nut chewing history had overall a younger age of onset (Mean age: 56.75 versus 52.68 yrs, P

The present study investigated clinical outcomes and prognostic factors of patients with locally advanced synchronous esophageal squamous cell carcinoma (ESCC) and head/neck squamous cell carcinoma (HNSCC) receiving curative concurrent chemoradiotherapy (CCRT), and determined whether synchronous ESCC/HNSCC patients had worse prognosis compared to isolated ESCC patients. Using propensity score matching method, we compared 60 locally advanced synchronous ESCC/HNSCC patients with 60 matched isolated ESCC patients. Compared to 60 matched isolated ESCC patients, synchronous ESCC/HNSCC patients had significantly worse prognosis (13.5 months versus 17.2 months, P = 0.01), more grade 3–4 CCRT toxicity, and higher percentage of CCRT interruption. For synchronous ESCC/HNSCC group, the 1-year and 2-year survival rates were 52% and 13%, respectively. Univariate analysis showed that early ESCC stage, non-T4b disease, and salvage operations were significantly associated with superior survival. In multivariate analysis, ESCC stage represented an independent prognosticator. For chemotherapy regimen during CCRT, cisplatin/5-fluorouracil had significantly more grade 3–4 mucositis/esophagitis and neutropenia than weekly cisplatin. In conclusion, synchronous ESCC/HNSCC patients receiving curative CCRT have worse prognosis and poorer compliance of CCRT compared to isolated ESCC patients. For these patients, ESCC stage and T4b disease were significantly associated with clinical outcomes, and salvage operation may improve overall survival.

SummaryFollicular thyroid carcinoma (FTC) with sternum metastasis is rarely reported. Conservative treatments always result in a poor prognosis. We report two cases of FTC presenting with a large symptomatic solitary metastatic lesion in the sternum. Surgical intervention included total thyroidectomy, combined with wide composite resection of the sternal manubrium, as well as the adjacent clavicular head and ribs. A large defect with exposed pericardium and great vessels was found post resection in both cases. Because the ipsilateral vessels were sacrificed, a contralateral extended pedicled pectoralis major adipofascial flap was designed and transposed to cover the underlying vital organs. The patients received both adjuvant I-131 and radiotherapy postoperatively. The treatment was uneventful, and the patients are well and asymptomatic 5 years after the treatment. Wide composite resection and appropriate adjuvant therapies may offer a survival benefit in patients with advanced FTC with sternum metastasis.

Background Accurate T-staging is pivotal for predicting prognosis and selecting appropriate therapies for esophageal squamous cell carcinoma (ESCC). The diagnostic performance of fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for its T-staging is uncertain. We investigated use of FDG PET/CT for preoperative T-staging of patients with ESCC. Methods Patients with ESCC given preoperative FDG PET/CT scans, either with (CRT[+] group) or without (CRT[−] group) neoadjuvant chemoradiotherapy, were retrospectively reviewed. Maximal standardized uptake value (SUVmax) of the primary tumors on FDG PET/CT scans were measured, and histopathological results were used as the reference standard. The associations between pathological T-stage and potential factors of age, tumor location, tumor grade, tumor size, and tumor SUVmax were analyzed. The cut-off levels of SUVmax for predicting different T-stages and for residual viable tumors after neoadjuvant chemoradiotherapy were determined using receiver operating characteristic analyses. Results We enrolled 103 patients (45 in the CRT[−] group; 58 in the CRT[+] group). SUVmax, an independent predictive factor, positively correlated with the pathological T-stage in both groups (CRT[−] group: ρ = 0.736, p 13.0) and 67.2% in the CRT[+] group (SUVmax of T0: 0–3.4, T1: 3.5–3.9, T2: 4.0–5.5, T3: 5.6–6.2, T4: > 6.2). For CRT[−] group, the accuracy using an SUVmax cut-off of 4.4 to differentiate early (T0-1) from locally advanced disease (T2-4) was 82.2% (95% CI, 71.1–93.4%). For CRT[+] group, the accuracy using an SUVmax cut-off of 3.4 to predict residual viable tumors (non-T0) after completion of chemoradiotherapy was 82.8% (95% CI, 73.0–92.5%). Conclusions The FDG avidity of a primary esophageal tumor significantly positively correlated with the pathological T-stage. PET/CT with thresholded SUVmax was useful for predicting T-stage and differentiating residual viable tumors. Electronic supplementary material The online version of this article (doi:10.1186/s12880-016-0171-7) contains supplementary material, which is available to authorized users.

One patient in the CRT[−] group with polypoid esophageal cancer and unexpectedly high fluorodeoxyglucose (FDG) avidity. Post-surgical histopathology proved the tumor to be stage T1. Representative (a) coronal (b) sagittal, and (c) transaxial computed tomography (CT), positron emission tomography (PET), and PET/CT fusion images (from left to right) showed a focal area of intensely increased FDG uptake in the lower thoracic esophagus (maximal standardized uptake value = 9.6); (d) endoscopy showed a polypoid tumor at about the 35 cm level from central incisors; and (e) endoscopic ultrasound showed the focal mucosal polypoid tumor (14.9 mm × 13.5 mm) invading the muscularis propria. (PDF 666 kb)

Background/Purpose Thymectomy may benefit patients with generalized myasthenia gravis (MG) or myasthenia with thymomas. Currently, video-assisted (VA) thoracic surgery is popular and plays an important role in thymectomy. We compared the clinical outcomes of VA thymectomy with conventional transsternal (TS) approach to investigate the effectiveness of VA technology in the current era. Methods A retrospective review of our thymectomy results for patients with MG from 1998 to 2011 was conducted. A total of 83 consecutive patients were enrolled. According to the surgeons’ and patients’ preference, 39 patients received conventional TS thymectomy and 44 were operated on in a VA fashion. The results were categorized and analyzed according to the Myasthenia Gravis Foundation of America (MGFA) postintervention statuses with some modification. Results No obvious difference between conventional TS thymectomy and VA thymectomy was noted regarding the remission statuses and the clinical outcomes by the modified MGFA score. However, the patients who received VA thymectomy showed shorter intensive care unit (ICU) stays (4.2 ± 3.3 days vs. 2.3 ± 1.5 days, p = 0.001). Conclusion Compared with the conventional TS thymectomy, the VA approach is similarly effective with shorter ICU stays.

The use of video-assisted thoracoscopic surgery (VATS) in patients with thymoma remains controversial. We sought to evaluate the perioperative and oncological outcomes after VATS resection for stage I and II thymoma and to compare the outcomes with those obtained after median sternotomy (MST). Between 1991 and 2007, a total of 140 patients with stage I and II thymoma underwent surgery at the Chang Gung Memorial Hospital. Of them, 58 underwent MST, 61 VATS, and 21 thoracotomy. Using a propensity score based on four variables (myasthenia gravis, tumor size on CT images, age, and Masaoka stage), 48 VATS-treated patients were matched to 48 patients who received MST. Outcomes compared included perioperative complications, length of stay, tumor recurrence, and survival. No operative deaths occurred in this study. VATS was associated with fewer intraoperative blood loss, and more patients in the VATS group were extubated in the operating room after surgery compared with the MST group (37.5 vs. 12.5 %, respectively, P = 0.005). The mean length of stay was shorter in the VATS group than in the MST group (5.8 vs. 7 days, respectively; P = 0.008). After a median follow-up of 53 months, five patients developed recurrent tumors (four pleural and one pericardial). No statistically significant differences were found in the 5-year survival rates between the two study groups. VATS appears feasible for patients with stage I and II thymoma and is associated with better perioperative outcomes than MST. The oncological outcomes are also similar.

Six new molecules with donor–acceptor–acceptor (D–A–A) configuration bearing coplanar electron-donating dithieno[3,2-b:2′,3′-d]pyrrole (DTP) or aryl-substituted DTP as the D unit and the electron-withdrawing pyrimidine–dicyanovinylene or benzothiadiazole–dicyanovinylene as the A–A block are synthesized. The introduction of aryl groups (p-tolyl or p-anisolyl) onto the α position of DTP is found to greatly benefit the chemical stability and extend the molecular conjugation of the DTP-based D–A–A molecules. The observed broad absorption spectra and anisotropic molecular orientation in the thin films allow for these new D–A–A molecules to perform good capability of light harvesting. These new D–A–A donors are subject to the fabrication of vacuum-processed small-molecule organic solar cells (SMOSCs). The results showed that the structural modulation on the central A block (pyrimidine versus benzothiadiazole) as well as the terminal substitution (p-tolyl versus p-anisolyl) give an evident trade-off between the ...

Piezoelectricity is a type of material that enables mechanical energy and electrical energy to be interchangeable, which can be divided into positive piezoelectric effect and inverse piezoelectric effect. The positive piezoelectric effect is that the electric dipole moment of material generates changes when the piezoelectric material is subjected to pressure, resulting in electrical energy. Conversely, the inverse piezoelectric effect is the process of electrical energy converted into mechanical energy.

Background Idiopathic azygos vein aneurysm (AVA) is rare. This retrospective study evaluated the imaging features and outcomes in 10 cases of idiopathic AVA. Methods We retrospectively evaluated 10 patients with surgically proven or typical imaging features of idiopathic AVA encountered in our institution between 1990 and 2012. Chest roentgenography and computed tomography (CT) were performed in all 10 patients, and magnetic resonance imaging (MRI) was performed in 4 of these patients. The clinical features, AVA morphologic characteristics, and outcomes were analyzed. Results Chest roentgenograms showed a right paratracheal nodule or mediastinal mass in 7 cases. CT and MRI disclosed 4 thrombosed saccular AVAs (short axis, 3–6 cm; mean, 4.7 cm) and 6 fusiform AVAs (short axis, 2.2–3 cm; mean 2.7 cm). Two large saccular AVAs that presented with chest tightness were resected shortly after diagnosis. One saccular AVA manifested as a pulmonary embolism, whereas the remaining AVA was asymptomatic; they showed 25% to 40% short-axis growth in a 3- to 5-year interval before subsequent AVA resection. Conversely, all 6 fusiform AVAs were asymptomatic and found incidentally, remaining rather stable with less than 8% short-axis growth during 3 to 8 years of follow-up. Compared with fusiform AVAs, saccular AVAs were larger and had a greater frequency of AVA-related symptoms, intralesional thromboses, and greater than 20% short-axis growth during the follow-up period. Conclusions Saccular AVAs are larger than fusiform aneurysms, presenting with greater frequency of chest symptoms, intralesional thrombosis, considerable lesion growth, and need for surgical intervention. In contrast, fusiform AVAs are asymptomatic and rather stable in long-term follow-up.

This study tested the hypothesis that tissue plasminogen activator (tPA) is crucial for regulating endothelial progenitor cell (EPC) mobilization from bone marrow to circulation in murine critical limb ischemia (CLI) by ligating the left femoral artery.Wild-type (C57BL/6) (n=40) mice were equally divided into group 1A (sham control), group 2A (CLI), group 3A [control-tPA (4.0 mg/kg)] and group 4A [CLI-tPA (intravenously at 3 h after CLI)]. Similarly, tPA knock-out (tPA(-/-)) mice (n=40) were equally divided into group 1B (sham control), group 2B (CLI), group 3B [control-tPA (4.0 mg/kg)], and group 4B (CLI-tPA).The circulating levels of EPCs (C-kit/CD31+, Sca-1/KDR+, CXCR4/CD34+) were lower in groups 1B and 2B than in groups 1A and 2A, respectively (all p0.01), and were reversed after tPA treatment (3B vs. 3A or 4B vs. 4A, p0.05) at 6 h and 18 h post-CLI. Levels of these biomarkers decreased again 14 days after CLI in tPA(-/-) mice compared to those in wild-type between the respective groups (all p0.01). Laser Doppler flowmetry showed a higher ratio of ischemic-to-normal blood flow in 2A than in 2B and in 4A than in 4B by day 14 after CLI (all p0.05). Angiogenesis at protein (CXCR4, SDF-1α, VEGF) and cellular (CXCR4+, SDF-1α+, and CD31+ cells) levels was highest in animals with CLI-tPA, significantly higher in mice with CLI only than in sham controls for both wild-type and tPA(-/-) mice (p0.01).tPA played an essential role in augmenting circulating EPCs, angiogenesis, and blood flow in the ischemic limb in a murine model.

We tested the hypothesis that Lipofectamine siRNA delivery to deplete transient receptor potential cation channel (TRPC) 1 protein expression can suppress hypoxia-induced pulmonary arterial hypertension (PAH) in mice. Adult male C57BL/6 mice were equally divided into group 1 (normal controls), group 2 (hypoxia), and group 3 (hypoxia + siRNA TRPC1). By day 28, right ventricular systolic pressure (RVSP), number of muscularized arteries, right ventricle (RV), and lung weights were increased in group 2 than in group 1 and reduced in group 3 compared with group 2. Pulmonary crowded score showed similar pattern, whereas number of alveolar sacs exhibited an opposite pattern compared to that of RVSP in all groups. Protein expressions of TRPCs, HIF-1α, Ku-70, apoptosis, and fibrosis and pulmonary mRNA expressions of inflammatory markers were similar pattern, whereas protein expressions of antifibrosis and VEGF were opposite to the pattern of RVSP. Cellular markers of pulmonary DNA damage, repair, and smooth muscle proliferation exhibited a pattern similar to that of RVSP. The mRNA expressions of proapoptotic and hypertrophy biomarkers displayed a similar pattern, whereas sarcomere length showed an opposite pattern compared to that of RVSP in all groups. Lipofectamine siRNA delivery effectively reduced TRPC1 expression, thereby attenuating PAH-associated RV and pulmonary arteriolar remodeling.

This study tested the hypothesis that combined therapy with nicorandil and colchicine is superior to either alone in attenuating monocrotaline (MCT)-induced rat pulmonary arterial hypertension (PAH). Adult male Sprague-Dawley rats (n=50) were equally randomized into group 1 (sham control), group 2 [MCT (60 mg/kg i.p.)], group 3 [MCT-Nicorandil (5.0 mg/kg/day)], group 4 [MCT-Colchicine (1.0 mg/kg/day)], and group 5 (MCT-Nicorandil-Colchicine). Drugs were given on day 5. All animals were sacrificed on day 90 after MCT administration. Right ventricular systolic blood pressure (RVSBP) and RV weight were increased in group 2 compared to group 1, reduced in groups 3 and 4 compared to group 2, and further reduced in group 5, whereas arterial-oxygen saturation showed an opposite pattern (all p

OBJECTIVES: Metachronous oesophageal squamous cell carcinoma (OSCC) has been increasing in long-term survivors of upper aerodigestive tract (UADT) cancers in recent years, but the treatment of such cases is not well established. The aim of this study was to compare the prognosis between patients with metachronous OSCC who had antecedent UADT cancers and patients with isolated OSCC. METHODS: From January 1995 to December 2009, we retrospectively compared the data from 84 patients with metachronous OSCC who had antecedent UADT cancers (metachronous group) with the data from 527 patients with isolated OSCC (isolated group) according to their treatment modalities at Kaohsiung Chang Gung Memorial Hospital. RESULTS: Overall, the metachronous group had significantly (P= 0.03) worse overall survival than the isolated group. For patients receiving surgery or preoperative chemoradiotherapy followed by surgery, the overall survival rates and incidence of postoperative complications were not significantly different. For patients receiving definite chemoradiotherapy or radiotherapy alone, the metachronous group had significantly (P= 0.02) inferior overall survival compared with the isolated group. CONCLUSIONS: Offering a radical approach for the treatment of patients with metachronous OSCC who had antecedent UADT cancers is justifiable, with survival rates similar to those of patients with isolated OSCC.

Background Lung cancer is the leading cause of cancer deaths in the world. Physical activity could help lung cancer patients improve their health. Objective The purpose of our study was to investigate lung cancer patients' physical activity preferences and relevant contributing factors, so that we could develop individualized intervention strategies to fit their needs. Methods This study used a descriptive and correlational design. Instruments included a physical activity preference survey form, the Physical Activity Social Support Scale, and Physical Activity Self-efficacy Scale. Results From 81 lung cancer patients' physical activity preferences, our results showed that during the course of their illness, 85.2% of patients wanted to have a physical activity consultation and preferred to obtain advice from their physicians (28.4%) through face-to-face counseling (48.1%). Moreover, patients (70.4%) showed an interest in physical activity programs, and many (69.1%) revealed that they were able to participate. About 88.9% of patients showed a preference for walking, and 54.3% patients preferred moderate physical activity. Conclusions This study also revealed that social support and self-efficacy for physical activity effectively predicted moderate physical activity preferences. Implications for practice The adherence to regular physical activity is improved by understanding the lung cancer patients' unique preferences for physical activity.

// Shau-Hsuan Li 1 , Hung-I Lu 2 , Alice Y.W. Chang 3 , Wan-Ting Huang 4 , Wei-Che Lin 5 , Ching-Chang Lee 6 , Wan-Yu Tien 1 , Ya-Chun Lan 1 , Hsin-Ting Tsai 3, 7, 8 , Chang-Han Chen 8, 9, 10 1 Department of Hematology-Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 2 Department of Thoracic & Cardiovascular Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 3 Institute of Physiology, National Cheng Kung University, Tainan, Taiwan 4 Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 5 Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 6 Department of Gastroenterology, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan 7 Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan, Taiwan 8 Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan 9 Department of Applied Chemistry, and Graduate Institute of Biomedicine and Biomedical Technology, National Chi Nan University, Taiwan 10 Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan Correspondence to: Chang-Han Chen, email: chench7@gmail.com Keywords: esophageal cancer, squamous cell carcinoma, AT1R, angiotensin II, mTOR Received: March 12, 2016 Accepted: August 11, 2016 Published: August 24, 2016 ABSTRACT Background: The aim of this study was to investigate the effects of the angiotensin II/ angiotensin II type I receptor (AT1R) and angiotensin II type II receptor (AT2R) signaling pathway in esophageal squamous cell carcinoma (ESCC). Methods: Immunohistochemistry was performed to evaluate the expression levels of AT1R and AT2R in tissues from 152 surgically resected ESCC patients, and those expression levels were then correlated with treatment outcomes. The angiotensin II/AT1R/AT2R signaling pathway and its biological effects in the context of ESCC were investigated in vitro and in vivo . Results: In human samples, AT1R overexpression was univariately associated with inferior overall survival and remained multivariately independent (hazard ratio=1.812). In vitro , angiotensin II stimulated the growth of ESCC cells in a dose-dependent manner. Treatment with irbesartan or AT1R-RNAi knockdown but not treatment with PD123319 significantly decreased the level of angiotensin II-induced ESCC cell proliferation. Angiotensin II also caused mTOR activation in a dose-dependent manner, and everolimus or mTOR-RNAi knockdown significantly suppressed the level of angiotensin II-induced ESCC cell proliferation. Furthermore, AT1R-RNAi knockdown suppressed the activation of mTOR. Clinically, AT1R expression was also correlated with phosphorylated mTOR expression. In a xenograft model, local angiotensin II injection enhanced tumor growth, and this effect could be decreased by treatment with irbesartan or everolimus. In a 4-NQO-induced-ESCC murine model, irbesartan significantly decreased the incidence of esophageal tumor. Conclusions: These findings suggest that AT1R overexpression is an independent adverse prognosticator for patients with ESCC and that angiotensin II/AT1R signaling stimulates ESCC growth, in part through mTOR activation.

This study tested the hypothesis that circulating microparticles (MPs) exacerbated vascular wall (VW) remodeling after endothelial denudation by 0.014 wire in a rat model. Adult male Sprague Dawley rats (n = 40) were equally categorized into group 1 [sham-control (SC); 3.0 mL saline intravenous injection], group 2 [SC + intravenous MPs (1.0 × 107) derived from patients with carotid artery stenosis (CAS)], group 3 [femoral arterial endothelial denudation (FAED)], group 4 (FAED + MPs derived from healthy subjects), and group 5 (FAED + CAS-derived MPs). Animals were euthanized by day 28 after FAED procedure. The results demonstrated that neointimal area (NIA) (mm2), medial area, and number of infiltrated cells in medial layer were highest in group 5 and lowest in groups 1 and 2, and significantly higher in group 4 than those in group 3 (all P

Background Radiofrequency catheter ablation for paroxysmal atrial fibrillation is well established but not drawback free. Pulmonary vein stenosis is one of the complications and usually treated with stenting with the disadvantages of high re-stenosis rate and anticoagulant dependence. Case presentation Herein, we present the case of a 47 year-old lady, who suffered from fever and hemoptysis due to right inferior pulmonary vein occlusion after radiofrequency catheter ablation for paroxysmal atrial fibrillation. Eventually, thoracoscopic right lower lung lobectomy was inevitable with satisfactory result. Conclusions Pulmonary vein stenosis is a major complication after radiofrequency ablation of atrial fibrillation. High suspicion and early detection in patients with pulmonary manifestations are mandatory for salvage the injured lung in early. If delayed, surgical resection of the involved lung, especially through the thoracoscopic approach will eradicate the problem with minimal complication.

F-18 fluorodeoxyglucose/Positron emission tomography/Solitary pulmonary nodules/Kinetic analysis. This study determined whether dynamic F-18 FDG PET imaging could differentiate benign from ma lignant solitary pulmonary nodules (SPNs). Histopathologically confirmed SPNs (10–35 mm), 24 malignant and 10 benign, from 34 patients were studied through both dynamic and static F-18 FDG PET imaging of all patients. Volumes of interest (VOIs) were placed over the pulmonary nodules using a 50% maximum pixel value threshold. The arterial input function was estimated from a left ventricle-defined VOI. Based on Patlak analysis, we calculated the net FDG phosphorylation rate (Ki) and glucose metabolic rate (MRGlu) of each nodule. The slope values o f the time-activity curves (TACs) of the nodules were also determined. Based on the static PET images, maximum and mean standardized uptake values (SUVmax and SUVmean, respectively) were calculated. Benign and malignant SPNs had significantly different values for SUVmax, SUVmean, Ki, MRGlu, and TAC slope, with area under the receiver operating characteristic curves distinguishing benign from malignant nodules. McNemar’s test of marginal homogeneity f ound all the predictors helpful to detect malignant nodules (all, p > 0.05), and combining Ki and MRGlu, which were generated by dynamic study, yielded a higher specificity of 90%, and a sensitivity of 79%. Among the 10 benign nodules, static SUV imaging correctly classified seven, while dynamic F-18 PET imaging correctly classified nine. Dynamic F-18 FDG PET imaging is valuable in differentiating benign from malignant SPNs, particularly for granulomatous disease.