Selenite selectively kills lung fibroblasts to treat bleomycin-induced pulmonary fibrosis.

BACKGROUND: Interstitial lung disease (ILD) treatment is a critical unmet need. Selenium is an essential trace element for human life and an antioxidant that activates glutathione, but the gap between its necessity and its toxicity is small and requires special attention. Whether selenium can be used in the treatment of ILD remains unclear. METHODS: We investigated the prophylactic and therapeutic effects of selenite, a selenium derivative, in ILD using a murine model of bleomycin-induced idiopathic pulmonary fibrosis (IPF). We further elucidated the underlying mechanism using in vitro cell models and examined their relevance in human tissue specimens. The therapeutic effect of selenite in bleomycin-administered mice was assessed by respiratory function and histochemical changes. Selenite-induced apoptosis and reactive oxygen species (ROS) production in murine lung fibroblasts were measured. RESULTS: Selenite, administered 1 day (inflammation phase) or 8 days (fibrotic phase) after bleomycin, prevented and treated deterioration of lung function and pulmonary fibrosis in mice. Mechanistically, selenite inhibited the proliferation and induced apoptosis of murine lung fibroblasts after bleomycin treatment both in vitro and in vivo. In addition, selenite upregulated glutathione reductase (GR) and thioredoxin reductase (TrxR) in murine lung fibroblasts, but not in lung epithelial cells, upon bleomycin treatment. GR and TrxR inhibition eliminates the therapeutic effects of selenite. Furthermore, we found that GR and TrxR were upregulated in the human lung fibroblasts of IPF patient samples. CONCLUSIONS: Selenite induces ROS production and apoptosis in murine lung fibroblasts through GR and TrxR upregulation, thereby providing a therapeutic effect in bleomycin-induced IPF.

Ex Vivo Evaluation of Combination Immunotherapy Using Tumor-Microenvironment-on-Chip.

Combination immunotherapy has emerged as a promising strategy to address the challenges associated with immune checkpoint inhibitor (ICI) therapy in breast cancer. The efficacy of combination immunotherapy hinges upon the intricate and dynamic nature of the tumor microenvironment (TME), characterized by cellular heterogeneity and molecular gradients. However, current methodologies for drug screening often fail to accurately replicate these complex conditions, resulting in limited predictive capacity for treatment outcomes. Here, a tumor-microenvironment-on-chip (TMoC), integrating a circulation system and ex vivo tissue culture with physiological oxygen and nutrient gradients, is described. This platform enables spatial infiltration of cytotoxic CD8+ T cells and their targeted attack on the tumor, while preserving the high complexity and heterogeneity of the TME. The TMoC is employed to assess the synergistic effect of five targeted therapy drugs and five chemotherapy drugs in combination with immunotherapy, demonstrating strong concordance between chip and animal model responses. The TMoC holds significant potential for advancing drug development and guiding clinical decision-making, as it offers valuable insights into the complex dynamics of the TME.

Cytotoxic T-lymphocyte antigen 4 polymorphisms and breast cancer susceptibility: Evidence from a meta-analysis.

BACKGROUND: Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is an immune checkpoint and regulates the immune function of T cells. However, previous findings regarding the association of CTLA-4 polymorphisms and breast cancer remain inconclusive. Therefore, we performed a meta-analysis to investigate the potential effects of five polymorphisms (-1722 T/C, -1661 A/G -318 C/T, +49 A/G, and CT60 A/G) in the CTLA-4 gene on breast cancer susceptibility. METHODS: Relevant literatures were systematically searched through electronic databases including PubMed, EMBASE, and Web of Science up to October 10, 2021. Available data were extracted and odds ratios (ORs) with 95% confidence intervals were used to estimate the pooling effect size. The Newcastle-Ottawa Scale was applied for assessing the quality of included studies. We conducted subgroup analyses based on ethnicity and control sources to explore levels of heterogeneity. Moreover, sensitivity analysis and publication bias were assessed. RESULTS: Finally, a total of 12 eligible studies regarding CTLA-4 polymorphisms and breast cancer were included. For overall analyses, only the +49 A/G polymorphism was significantly associated with breast cancer under allelic (OR = 1.19), dominant (OR = 1.27), and recessive (OR = 1.27) models. Ethnicity-based subgroup analysis found that the +49 A/G polymorphism has a significant risk (OR = 2.03) of breast cancer under the recessive model in the non-Asian population. Studies with hospital-based controls showed that the +49 A/G polymorphism has significant breast cancer risks under allelic (OR = 1.44), dominant (OR = 1.86), and recessive (OR = 1.60) models. In addition, those with population-based controls found that -1722 T/C polymorphism has a significant breast cancer risk under allelic (OR = 1.19) and dominant (OR = 1.26) models. CONCLUSION: This meta-analysis suggested that CTLA-4 + 49 A/G polymorphism may significantly associate with breast cancer susceptibility. Future studies containing various populations are helpful for evaluating the impacts of CTLA-4 polymorphisms on breast cancer susceptibility.

Glutathione peroxidase 4 expression predicts poor overall survival in patients with resected lung adenocarcinoma.

This study aimed to evaluate the protein expression of glutathione peroxidase 4 (GPX4) in resected non-small cell lung cancer (NSCLC). The clinical relevance and prognostic significance of GPX4 expression were analyzed. We reviewed patients with resected NSCLCs at Taipei Veterans General Hospital between September 2002 and January 2018. Available paraffin-embedded specimens were retrieved for immunohistochemistry (IHC) staining to detect GPX4 expression. The cutoff value for defining GPX4 positivity was determined according to the percentage of tumor stained in the microscopic field. The correlation between immune expression, clinicopathologic data, overall survival (OS), and disease-free survival (DFS) were analyzed. A total of 265 NSCLC specimens were retrieved for IHC staining. GPX4 expression positive was in 192 (72.5%) according to a cutoff value of 5%. GPX4 was a significant prognostic factor for OS and DFS on multivariate analysis at both 5% and 25% cutoff values. GPX4 expression was associated with poor OS and DFS, especially in lung adenocarcinoma (p = 0.008, and 0.027, respectively). In conclusions, IHC analysis revealed that GPX4 expression was associated with poor survival outcomes in patients with resected lung adenocarcinoma. Further research is needed to understand the role of GPX4 in tumorigenesis and the underlying mechanism responsible for survival outcomes in patients with resected lung adenocarcinoma.

Drainless thoracoscopic surgery should be avoided in primary spontaneous pneumothorax with pleural adhesion.

OBJECTIVES: Drainless thoracoscopic surgery, defined by omitting chest drain after surgery, has been demonstrated to be feasible in selected patients for pulmonary resection. However, drainless procedure for the treatment of primary spontaneous pneumothorax has raised concerns for its safety and thus has been less often reported. We aimed to share our preliminary experience regarding how to select patients with spontaneous pneumothorax for this procedure. METHODS: A retrospective study recruiting 303 consecutive patients with the diagnosis of spontaneous pneumothorax undergoing thoracoscopic surgery in our centre from August 2016 to June 2020 was done. After careful selection, the chest drain was omitted in selected patients who underwent non-intubated uniportal thoracoscopic surgery. Patients' clinical characteristics and perioperative outcomes were analysed. RESULTS: A total of 34 patients underwent drainless thoracoscopic surgery for the treatment of spontaneous pneumothorax. Pleural adhesion was noted in 9 patients during surgery, and all of them (100%) developed residual pneumothorax, among which intercostal drainage was required in 2 (22.2%) patients and ipsilateral pneumothorax recurred 3 years after surgery in 1 (11.1%) patient. Among the remaining 25 without pleural adhesion, 17 (68.0%) developed minor residual pneumothorax (P = 0.006), which all resolved spontaneously within 1-2 weeks, with no complications or recurrence during postoperative follow-up for at least 2 years. CONCLUSIONS: Drainless thoracoscopic surgery for the treatment of primary spontaneous pneumothorax is feasible but can be risky without careful patient selection. In our experience, the drainless procedure should be avoided in patients with identifiable pleural adhesion noted during surgery.

Endoscopic Screening for Second Primary Tumors of the Esophagus Among Head and Neck Cancer Patients.

Malignancies of the head and neck (HN) region and esophagus are among the most common cancers worldwide. Due to exposure to common carcinogens and the theory of field cancerization, HN cancer patients have a high risk of developing second primary tumors (SPTs). In our review of 28 studies with 51,454 HN cancer patients, the prevalence of SPTs was 12%. The HN area is the most common site of SPTs, followed by the lungs and esophagus, and 13% of HN cancer patients have been reported to have esophageal high-grade dysplasia or invasive carcinoma. The prognosis of HN cancer patients with concomitant esophageal SPTs is poor, and therefore identifying esophageal SPTs as early as possible is of paramount importance for risk stratification and to guide the treatment strategy. Image-enhanced endoscopy, especially using narrow-band imaging endoscopy and Lugol's chromoendoscopy, has been shown to improve the diagnostic performance in detecting esophageal neoplasms at an early stage. Moreover, the early detection and minimally invasive endoscopic treatment of early esophageal neoplasm has been shown to improve the prognosis. Well-designed prospective studies are warranted to establish appropriate treatment and surveillance programs for HN cancer patients with esophageal SPTs.

Molecular target therapeutics of EGF-TKI and downstream signaling pathways in non-small cell lung cancers.

Lung carcinoma (LC) is the third most common cancer diagnosis and accounted for the most cancer-related mortality worldwide in 2018. Based on the type of cells from which it originates, LC is commonly classified into non-small cell lung cancers (NSCLC) and small cell lung cancers (SCLC). NSCLC account for the majority of LC and can be further categories into adenocarcinoma, large cell carcinoma, and squamous cell carcinoma. Accurate classification of LC is critical for its adequate treatment and therapeutic outcome. Since NSCLC express more epidermal growth factor receptor (EGFR) with activation mutations, targeted therapy EGFR-tyrosine kinase inhibitors (TKIs) have been considered as primary option of NSCLC patients with activation EGFR mutation. In this review, we present the genetic alterations, reported mutations in EGFR, and TKIs treatment in NSCLC patients with an emphasis on the downstream signaling pathways in NSCLC progression. Among the signaling pathways identified, mitogen activation protein kinase (MAPK), known also as extracellular signal-regulated protein kinase (Erk) pathway, is the most investigated among the related pathways. EGFR activation leads to the autophosphorylation of its kinase domain and subsequent activation of Ras, phosphorylation of Raf and MEK1/2, and the activation of ERK1/2. Phosphatidylinositol 3-kinase (PI3K)/Akt is another signal pathway that regulates cell cycle and has been linked to NSCLC progression. Currently, three generations of EGFR TKIs have been developed as a first-line treatment of NSCLC patients with EGFR activation and mutation in which these treatment options will be further discussed in this review. The Supplementary Appendix for this article is available at http://links.lww.com/JCMA/A138.

Factors Associated with Nodal Upstaging in Clinical T1a-bN0M0 Non-Small Cell Lung Cancers.

Nodal upstaging of lung adenocarcinoma occurs when unexpected pathological lymph node metastasis is found after surgical intervention, and may be associated with a worse prognosis. In this study, we aimed to determine the predictive factors of nodal upstaging in cT1a-bN0M0 primary lung adenocarcinoma. We retrospectively reviewed a prospective database (January 2011 to May 2017) at National Taiwan University Hospital and identified patients with cT1a-bN0M0 (solid part tumor diameter ≤ 2 cm) lung adenocarcinoma who underwent video-assisted thoracoscopic lobectomy. Logistic regression models and survival analysis were used to examine and compare the predictive factors of nodal upstaging. A total of 352 patients were included. Among them, 28 (7.8%) patients had nodal upstaging. Abnormal preoperative serum carcinoembryonic antigen (CEA) levels, solid part tumor diameter ≥ 1.3 cm, and consolidation-tumor (C/T) ratio ≥ 0.50 on chest computed tomography (CT) were significant predictive factors associated with nodal upstaging, and patients with nodal upstaging tended to have worse survival. Standard lobectomy is recommended for patients with these predictive factors. If neither of the predictive factors are positive, a less invasive procedure may be a reasonable alternative. Further studies are needed to verify these data.

Nanodiamond-based microRNA delivery system promotes pluripotent stem cells toward myocardiogenic reprogramming.

BACKGROUND: Gene therapy is the advanced therapeutics for supplying or replacing the genetic material in patients with inherited disorders. Recent clinical studies have made some progress in a wide range of applications, including monogenic disorders, neurodegenerative diseases, malignant tumors, and congenital diseases. Heart diseases, especially myocardial ischemia, remain one of the leading causes of mortality worldwide and usually result in irreparable cardiomyocyte damage and severe heart failure. METHODS: Most advances in induced pluripotent stem cell (iPSC) technologies for promoting regenerative medicine and stem cell research. However, the driver molecules of myocardial-lineage differentiation and the functional reconstruction capacity of iPSC-derived cardiomyocytes are still an open question. Nanomedicine-based gene delivery provided a crucial platform to carry on the biogenomic materials for equipping functionalities and engineering the living organ environment. Nanodiamond (ND), a carbon-based nanomaterial, has been discovered and shown the high biocompatible and less toxicity for transporting protein, drug, and genomic plasmids. RESULTS: Here, we applied ND as a gene delivery vehicle to carry microRNA (miR-181a), and then transfected into iPS to promote cardiomyocyte-lineage differentiation. Notably, miR-181a plays a key role in iPS-derived cardiomyocyte differentiation which directly targets Hox-A11, leading to elevated MyoD expression and enhanced cardiomyocyte differentiation. CONCLUSION: Our study demonstrated that miR-181a promotes iPSC differentiation into functional cardiomyocytes. Delivery of NANO-DIAMOND-miR-181a may host clinical potential to enhance the differentiation and recovery of the cardiogenic function in injured cardiomyocytes.

Generation of osimertinib-resistant cells from epidermal growth factor receptor L858R/T790M mutant non-small cell lung carcinoma cell line.

BACKGROUND: Lung cancer contributes to high cancer mortality worldwide with 80% of total cases diagnosed as non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) tyrosine kinase (TK) domain serves as a druggable target in NSCLC patients with exon 19 deletion and L858R mutation. However, patients eventually succumbed to resistance to first- and second-generation EGFR-TK inhibitors through activation of T790M mutation. Third-generation EGFR-TKI, Osimertinib exhibits high efficacy in patients with exon 19 deletion/L858R/T790M mutation but they experienced acquired resistance thereafter. Available treatment options in NSCLC patients remains a challenge due to unknown molecular heterogeneity responsible for acquired resistance to EGFR-TKI. In this study, we aim to generate Osimertinib-resistant (OR) cells from H1975 carrying L858R/T790M double mutation which can be used as a model to elucidate mechanism of resistance. METHODS: OR cells were established via stepwise-dose escalation and limiting single-cell dilution method. We then evaluated Osimertinib resistance potential via cell viability assay. Proteins expression related to EGFR-signalling, epithelial to mesenchymal transition (EMT), and autophagy were analyzed via western blot. RESULTS: OR cell lines exhibited increased drug resistance potential compared to H1975. Distinguishable mesenchymal-like features were observed in OR cells. Protein expression analysis revealed EGFR-independent signaling involved in the derived OR cells as well as EMT and autophagy activity. CONCLUSION: We generated OR cell lines in-vitro as evidenced by increased drug resistance potential, increased mesenchymal features, and enhanced autophagy activity. Development of Osimertinib resistance cells may serve as in-vitro model facilitating discovery of molecular aberration present during acquired mechanism of resistance.

Vicryl Mesh Coverage Reduced Recurrence After Bullectomy for Primary Spontaneous Pneumothorax.

BACKGROUND: Although thoracoscopic stapled bullectomy is a standard procedure for primary spontaneous pneumothorax (PSP), the postoperative recurrence rate is high. We investigated whether using a Vicryl (Ethicon, Somerville, NJ) mesh to cover the staple line after bullectomy reduces the postoperative recurrence rate. METHODS: Our single-blind, parallel-group, prospective, randomized controlled trial at 2 medical centers in Taiwan studied patients with PSP who were aged 15 to 50 years and required thoracoscopic bullectomy. On the day of operation, patients were randomly assigned (1:1) to receive Vicryl mesh (mesh group) or not (control group) after thoracoscopic bullectomy with linear stapling and mechanical apical pleural abrasion. Randomization was achieved using computer-generated random numbers in sealed envelopes. Our primary end point was the pneumothorax recurrence rate within 1 year after the operation (clinicaltrials.gov number, NCT01848860.) RESULTS: Between June 2013 and March 2016, 102 patients were assigned to the mesh group and 102 to the control group. Within 1 year after operation, recurrent pneumothorax was diagnosed in 3 patients (2.9%) in the mesh group compared with 16 (15.7%) in the control group (P = .005). The short-term postoperative results and hospitalization duration were comparable between the groups. CONCLUSIONS: For thoracoscopic bullectomy with linear stapling and mechanical apical pleural abrasion, the use of a Vicryl mesh to cover the staple line is effective for reducing the postoperative recurrence of pneumothorax. Vicryl mesh coverage can be considered an optimal adjunct to the standard surgical procedure for PSP.

Plasma Level of Circular RNA hsa_circ_0000190 Correlates with Tumor Progression and Poor Treatment Response in Advanced Lung Cancers.

Lung cancer (LC) causes the majority of cancer-related deaths. Circular RNAs (circRNAs) were reported to play roles in cancers by targeting pro- and anti-oncogenic miRNAs. However, the mechanisms of circRNAs in LC progression and their prognostic value of treatment response remain unclear. By using next generation sequencing (NGS) of LC cell lines' transcriptomes, we identified highly overexpressed hsa_circ_0000190 and hsa_circ_000164 as potential biomarkers. By using the highly sensitive RT-ddPCR method, these circRNAs were shown to be secreted by cell lines and were detected in human blood. Clinical validation by RT-ddPCR was carried out on 272 (231 LC patients and 41 controls) blood samples. Higher hsa_circ_0000190 levels were associated with larger tumor size (p < 0.0001), worse histological type of adenocarcinoma (p = 0.0028), later stage (p < 0.0001), more distant metastatic organs (p = 0.0039), extrathoracic metastasis (p = 0.0004), and poor survival (p = 0.047) and prognosis. Using liquid biopsy-based RT-ddPCR, we discovered the correlation between increased hsa_circ_0000190 plasma level (p < 0.0001) and higher programmed death-ligand 1 (PD-L1) level in tumor (p = 0.0283). Notably, long-term follow-up of the immunotherapy treated cases showed that upregulated plasma hsa_circ_0000190 level correlated with poor response to systemic therapy and immunotherapy (p = 0.0002, 0.0058, respectively). Secretory circRNAs are detectable in blood by LB-based RT-ddPCR and may serve as blood-based biomarkers to monitor disease progression and treatment efficacy.

Is tubeless uniportal video-assisted thoracic surgery for pulmonary wedge resection a safe procedure?

OBJECTIVES: Tubeless uniportal video-assisted thoracic surgery (VATS), using a uniportal approach and non-intubated anaesthesia while avoiding postoperative chest drain insertion, for patients undergoing thoracoscopic surgery has been demonstrated to be feasible in selected cases. However, to date, the safety of the procedure has not been studied. METHODS: We reviewed consecutive patients undergoing non-intubated uniportal VATS for pulmonary wedge resection at 2 medical centres between August 2016 and October 2019. The decision to avoid chest drain insertion was made in selected candidates. For those candidates in whom a tubeless procedure was performed, postoperative chest X-rays (CXRs) were taken on the day of the surgery [operation (OP) day], on postoperative day 1 and 1-2 weeks later. The factors associated with abnormal CXR findings were studied. RESULTS: Among 135 attempts to avoid chest drain insertion, 13 (9.6%) patients ultimately required a postoperative chest drain. Among 122 patients in which a tubeless procedure was performed, 26 (21.3%) and 47 (38.5%) had abnormal CXR findings on OP day and postoperative day 1, respectively. Among them, 3 (2.5%) patients developed clinically significant abnormal CXRs and required intercostal drainage. Primary spontaneous pneumothorax was independently associated with a higher risk of postoperative abnormal CXRs. CONCLUSIONS: Tubeless uniportal VATS for pulmonary wedge resection can be safely performed in selected patients. Most patients with postoperative abnormal CXRs presented subclinical symptoms that spontaneously resolved; only 2.5% of patients with postoperative abnormal CXRs required drainage.

CircularRNA as novel biomarkers in liver diseases.

The liver is an essential organ that is primarily responsible for digestion and eliminating toxic substances from the body. After the industrial revolution, Western diet and lifestyle changes have increased the incidence of several liver diseases, including non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), liver cirrhosis, and hepatocellular carcinoma (HCC). NAFLD and NASH are mostly asymptomatic at early stages, and the disease progression from NAFLD to life-threatening HCC remains not fully understood. Circular RNA (circRNA) is consist of a circular structure, and the circRNA-microRNA(miRNA)-mRNA axes have been shown to be involved in several cellular events, including apoptosis, vascularization, metastasis, etc. The highly stable structure of circRNAs has enabled themselves to be used as putative biomarkers of several diseases. Here, we conducted a literature review and discussed the identified roles of circRNAs in NAFLD, NASH, liver cirrhosis, and HCC. For example, deficiency of circRNA_0046366 and circRNA_0046367 has been shown as the characteristics of NAFLD, and restoration of these circRNAs ameliorates the oxidative stress, lipotoxicity, and disease severity in NAFLD. Silencing of circ_0071410 was shown to alleviate hepatic stellate activation, the key step of liver cirrhosis. CDR1 and circ_0067934 can facilitate the invasion and metastasis of HCC, while circMTO1 negatively regulates the progression of HCC. Although several research works have been conducted, the whole picture of circRNA-related underlying mechanisms is unclear. Future works using high-throughput bioinformatic approaches will be needed to delineate the role of circRNAs in liver diseases and to further develop novel diagnostics and therapeutics.

Nanoparticle-delivery system enhanced the improvement and recovery in toxicity-induced acute hepatic failure.

BACKGROUND: The major curative remedy for advanced liver failure is hepatic transplantation. However, the conventional medicine still shows the limitations and obstacles for liver regeneration. Importantly, it is unclear whether we can get a rapid and high efficacy platform to facilitate to reprogram hepatic capability. The main work of this study was to develop a platform for a nanomedicine-based gene-delivery platform of novel nanoparticles (NNPs) to efficiently facilitate the liver function recovery. METHODS: In this study, we studied the feasibility and efficiency of NNP and produced the multiple abilities of NNPs for a potential platform of gene transduction. We showed that NNPs played an important role in hepatic protection. The cytoprotective effects of NNPs in toxic-hepatic cells were investigated and evaluated by cell viability, reactive oxygen species production, in vitro cell abilities, and in vivo animal studies. RESULTS: We demonstrated that NNPs possess the abilities to protect the cell after toxic-stress both in vitro and in vivo. Under the stress condition, our result showed that cell viabilities can be improved by NNP-carried hepatocyte nuclear factor 3 (HNF3) gene (NNP-HNF3), which is a famous hepatic transcriptional factor and regenerative marker to modulate essential molecular pathways activating various hepatic-specific markers. Importantly, compared to control and NNP-control, NNP-HNF3 exhibited the cytoprotective effects that prevented toxic-induced oxidative stress and cell damage in vitro as well as in vivo. Notably, our data showed that NNP-HNF3 treatment may improve toxic-induced hepatic encephalopathy. CONCLUSION: Herein, we demonstrated that novel nanoparticle, such as NNP-HNF3, serves as a key regulator for protecting the damaged hepatic cell and the bioproduct-based source for the new therapeutics of hepatic failure.

The subpopulation of CD44-positive cells promoted tumorigenicity and metastatic ability in lung adenocarcinoma.

BACKGROUND: Lung cancer is one of the major causes of carcinoma-related deaths in the world. Importantly, lung adenocarcinoma (LAC) is the most common type with poor outcome. However, the progressive clinical phenotype and biomolecular signature of lung cancer presenting the cancer stem-like and metastatic characteristics are still unclear. METHODS: In this study, we identified CD44 marker in lung cancers. The capabilities, including tumorigenic and migration assays, were analyzed in CD44 expression and CD44 expression subgroups. Meanwhile, the potential bio-signature and properties of lung tumor stem-like cells were further studied. RESULTS: The high expression of CD44 subpopulation (CD44-positive) in isolated lung cancer cells showed significantly higher abilities of tumorigenic colonies, tumor-sphere formation, and migratory properties when compared with the CD44 expression group. These subgroups of CD44-positive lung cancer cells further demonstrated the metastatic potential with epithelial-mesenchymal transition (EMT), as well as the high expression of Twist and Snail gene profile. Importantly, the overexpression of Snail with gene vector in CD44 expression cells further significantly promoted the properties of lung tumor stem-like cells. CONCLUSION: The results of this study highlighted the role of CD44-posivite subpopulation in modulating tumor initiation and EMT-based metastatic ability of lung malignancy.

Tubeless single-port thoracoscopic sublobar resection: indication and safety.

BACKGROUND: The tubeless technique, defined as non-intubated general anesthesia with omission of chest drainage after video-assisted thoracoscopic surgery (VATS), is a new concept to further minimize surgical trauma. However, there has been little investigation into the associated feasibility and safety. Minimization of postoperative pneumothorax is challenging. We set up a "tubeless protocol" to select patients for tubeless single-port VATS with monitoring of a digital drainage system (DDS). METHODS: From November 2016 to September 2017, 50 consecutive non-intubated single-port VATS for pulmonary resection were performed. In our study, patients with small and peripheral pulmonary lesions indicated for sublobar resections, as diagnostic or curative intent, were included. After excluding patients having tumors >2 cm, or intrapleural adhesions noted during operation, or forced expiratory volume in the 1 second <1.5 L, 36 patients were selected for tubeless protocol. The clinical characteristics and perioperative outcomes of these patients are presented. RESULTS: Among 36 cases, 5 patients had minor air leaks detected using the DDS and required intercostal drainage after wound closure. Among the remaining 31 patients in whom the DDS showed no air leak, the chest drainage was removed immediately after wound closure. A postoperative chest roentgenogram on the surgery day showed full expansion in all patients without pneumothorax. Only 7 (19.4%) patients developed minor subclinical pneumothorax on the first postoperative day without the need for chest drainage. All patients were discharged uneventfully without the need for intervention. CONCLUSIONS: Our tubeless protocol utilizes DDS to select patients who can have intercostal drainage omitted after non-intubated single-port VATS for pulmonary resection. Using objective DDS parameters, we believe that this is an effective way to reduce the rate of pneumothorax after tubeless single-port VATS in selected patients.

Esophageal Metal Stents with Concurrent Chemoradiation Therapy for Locally Advanced Esophageal Cancer: Safe or Not?

BACKGROUND: The purpose of this study was to review the risks and benefits of concurrent chemoradiation therapy (CCRT) with esophageal self-expandable metal stents (SEMS) for the treatment of locally advanced esophageal cancer. MATERIALS AND METHODS: Between January 2014 and December 2016, the data from 46 locally advanced esophageal cancer patients who received CCRT at our institution were retrospectively reviewed. Eight patients who received CCRT concomitant with SEMS placement (SEMS plus CCRT group) and thirty-eight patients who received CCRT without SEMS placement (CCRT group) were identified. The risk of developing esophageal fistula and the overall survival of the two groups were analyzed. RESULTS: The rate of esophageal fistula formation during or after CCRT was 87.5% in the SEMS plus CCRT group and 2.6% in the CCRT group. The median doses of radiotherapy in the SEMS plus CCRT group and the CCRT group were 47.5 Gy and 50 Gy, respectively. SEMS combined with CCRT was associated with a greater risk of esophageal fistula formation than CCRT alone (hazard ratio [HR], 72.30; 95% confidence interval [CI], 8.62-606.12; p < .001). The median overall survival times in the SEMS plus CCRT and CCRT groups were 6 months and 16 months, respectively. Overall survival was significantly worse in the SEMS plus CCRT group than in the CCRT group (HR, 5.72; 95% CI, 2.15-15.21; p < .001). CONCLUSION: CCRT concomitant with SEMS for locally advanced esophageal cancer results in earlier life-threatening morbidity and a higher mortality rate than treatment with CCRT alone. Further prospective and randomized studies are warranted to confirm these observations. IMPLICATIONS FOR PRACTICE: Patients treated with SEMS placement followed by CCRT had higher risk of esophageal fistula formation and inferior overall survival rate compared with patients treated with CCRT alone. SEMS placement should be performed cautiously in patients who are scheduled to receive CCRT with curative intent.

Cost-Effectiveness of Minimally Invasive Esophagectomy for Esophageal Squamous Cell Carcinoma.

INTRODUCTION: The cost-effectiveness of minimally invasive esophagectomy (MIE) versus open esophagectomy (OE) for esophageal squamous cell carcinoma (ESCC) has not been established. Recent cost studies have shown that MIE is associated with a higher surgical expense, which is not consistently offset by savings through expedited post-operative recovery, therefore suggesting a questionable benefit of MIE over OE from an economic point of view. In the current study, we compared the cost-effectiveness of MIE versus OE for ESCC. MATERIALS AND METHODS: Between April 2000 and December 2013, a total of 251 consecutive patients undergoing MIE or OE for ESCC were enrolled. After propensity score (PS)-matching the MIE group with the OE group for clinical characteristics, 95 patients from each group were enrolled to compare the peri-operative outcomes, long-term survival, and cost. RESULTS: After PS-matching, the baseline characteristics were not significantly different between groups. Perioperative outcomes were similar in both groups. MIE was superior to OE with respect to a shorter intensive care unit (ICU) stay, while the complication rate (except for hoarseness) and survival were similar. Post-operative cost was significantly less in the MIE group due to a shorter ICU stay; however, reduced post-operative cost failed to offset the higher surgical expense of MIE. CONCLUSIONS: MIE for ESCC failed to show cost-effectiveness regarding overall expense in our study, but costs less in the postoperative care, especially for ICU care. More cost studies on MIE in other health care systems are warranted to verify the cost-effectiveness of MIE.

Prognostic role of initial pan-endoscopic tumor length at diagnosis in operable esophageal squamous cell carcinoma undergoing esophagectomy with or without neoadjuvant concurrent chemoradiotherapy.

BACKGROUND: The objective of this study was to appraise the prognostic role of initial pan-endoscopic tumor length at diagnosis within or between operable esophageal squamous cell carcinoma (ESCC) undergoing upfront esophagectomy or neoadjuvant concurrent chemoradiotherapy (nCCRT) followed by esophagectomy. METHODS: Between Jan 2001 and Dec 2013 in Koo-Foundation Sun Yat-sen Cancer Center in Taiwan, 101 ESCC patients who underwent upfront esophagectomy (surgery group) and 128 nCCRT followed by esophagectomy (nCCRT-surgery group) were retrospectively collected. Prognostic variables, including initial pan-endoscopic tumor length at diagnosis (sub-grouped ≤3, 3-5 and >5 cm), status of circumferential resection margin (CRM), and pathological T/N/M-status and cancer stage, were appraised within or between surgery and nCCRT-surgery groups. RESULTS: Within surgery group, longer initial pan-endoscopic tumor length at diagnosis (≤3, 3-5 and >5 cm; HR =1.000, 1.688 and 4.165; P=0.007) was an independent prognostic factor that correlated with advanced T/N/M-status, late cancer stage, and CRM invasion (all's P<0.001). Based on the initial pan-endoscopic tumor length at diagnosis ≤3, 3-5 and >5 cm, nCCRT-surgery group had a poorer (P=0.039), similar (P=0.447) and better (P<0.001) survivals than did surgery group, respectively. For those with initial pan-endoscopic tumor length at diagnosis >5 cm, nCCRT-surgery group had more percentage of T0/N0-status and stage 0 (all's P<0.05), and fewer rate of CRM invasion (P=0.036) than did surgery group. CONCLUSIONS: Initial pan-endoscopic tumor length at diagnosis could be a criterion to select proper ESCC cases for nCCRT followed by esophagectomy to improve survival and reduce CRM invasion.