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Introduction: The use of stereotactic ablative radiotherapy (SABR) over conventional fractionated radiotherapy (CFRT) for early-stage non-small-cell lung cancer (NSCLC) has been advocated, but is also debated in the literature., Methods: In this retrospective cohort study, we adopted a target trial emulation framework to identify eligible patients diagnosed between 2011 and 2021 using the Taiwan Cancer Registry. In the primary analysis, the overall survival (OS) was the primary endpoint, whereas incidences of lung cancer mortality and radiation pulmonary toxicity were the secondary endpoints. Extensive supplementary analyses were also conducted., Results: We included 351 patients in the primary analysis and found that the OS was not significantly different between the SABR (n = 290) and CFRT (n = 61) groups. The propensity score weighting adjusted hazard ratio of death was 0.75 (95% confidence interval 0.53-1.07, p = 0.118). The secondary endpoints and supplementary analyses showed no significant differences., Conclusions: The OS of patients with early-stage NSCLC treated with SABR was not significantly different from that of patients treated with CFRT alone. The results of the relevant ongoing clinical trials are eagerly awaited., (© 2024 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

Background: In the context of progressively uncontrolled drug resistance of bacteria, the difficulty of treating Klebsiella (KP)-induced pneumonia increases. Searching for drugs other than antibiotics has become an urgent task. Vitamin D (VD), meanwhile, is shown to be capable of treating pneumonia. Therefore, we aimed to explore the effects and mechanisms of VD on KP-infected rats., Methods: Male Sprague Dawley rats were divided into the Control, VD, KP and KP+VD groups. A rat pneumonia model was induced using an intratracheal drop of 2.4×10 8 CFU/mL KP. VD treatment was performed by gavage using 5 μg/kg. Subsequently, the survival of the rats was recorded, and the lungs, bronchoalveolar lavage fluid, and feces of the rats were collected 4 days after KP infection. Next, the water content of lung tissues was measured by the wet-to-dry weight ratio. Histopathological changes of lung tissues were observed by Hematoxylin and Eosin staining and the levels of inflammatory factors (TNF-α, IL-1β, MCP1) were detected using ELISA. The feces of rats in each group were also subjected to 16S rDNA gene analysis of intestinal microbiota., Results: Compared with the KP group, the KP+VD group showed a significant increase in survival, a significant decrease in water content and bacterial counts in the lungs, a significant improvement in lung injury, and a significant decline in the levels of TNF-α, IL-1β, and MCP1. According to the 16S rDNA sequencing, VD altered the structure of the intestinal bacterial community in the KP-infected rats and made the species richness similar to that of healthy rats. Additionally, the abundance of Anaeroglobus was significantly increased in the KP+VD group., Conclusion: VD modulates intestinal microbiota to increase the resistance of rats to pneumonia caused by Klebsiella infection., Competing Interests: The authors declare that they have no competing interests in this work., (© 2024 Hu et al.)

Background: The role of consolidative chemotherapy (CCT) for locally advanced esophageal squamous cell carcinoma (LA-ESCC) patients treated with definitive concurrent chemoradiotherapy (dCCRT) is unclear. We aimed to compare the overall survival (OS) of those treated with vs without CCT via a population based approach., Methods: Eligible LA-ESCC patients diagnosed between 2011 and 2017 were identified via the Taiwan Cancer Registry. We used propensity score (PS) weighting to balance observable potential confounders between groups. The hazard ratio (HR) of death and incidence of esophageal cancer mortality (IECM) were compared between those with vs without CCT. We also evaluated the OS in supplementary analyses via alternative approaches., Results: Our primary analysis consisted of 368 patients in whom covariates were well balanced after PS weighting. The HR of death when CCT was compared to without was 0.67 (95% confidence interval 0.52-0.86, P = 0.002). The HR of IECM was 0.66 (P = 0.04). The HR of OS remained similarly in favor of CCT in supplementary analyses., Conclusions: We found that CCT was associated with significantly improved OS for LA-ESCC patients treated with dCCRT. Randomized controlled trials were needed to confirm this finding., (© 2022. The Author(s).)

Background: The role of adjuvant concurrent chemoradiotherapy (ACCRT) is unclear for patients with esophageal squamous cell carcinoma (ESCC) who receive esophagectomy with clean margins. We compared the survival of the ACCRT versus observation groups for these patients staged with positron emission tomography (PET) via a population-based approach., Methods: Eligible patients with locally advanced ESCC diagnosed between 2011 and 2017 were identified via the Taiwan Cancer Registry. We used propensity score (PS) weighting to balance observable potential confounders between groups. The hazard ratios (HR) of death and incidence of esophageal cancer mortality (IECM) were compared between the ACCRT and observation groups. We also evaluated overall survival (OS) in subgroups of either with or without lymph node metastases., Results: Our primary analysis consisted of 105 patients in whom the covariates were well balanced after PS weighting. The HR for death when ACCRT was compared with observation was 0.58 (95% confidence interval 0.28-1.21, p = 0.15). The results were also not significantly different for IECM or in the subgroup analyses., Conclusion: We found that for patients with PET-staged ESCC who received esophagectomy with clean margins, the survival was not statistically different between ACCRT and observation. Further studies (randomized or larger sample size) are needed to clarify this issue., (© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Objectives: Blunt chest trauma is often associated with severe pain, reduced lung function and decreased sleep quality. This study aims to investigate the immediate and long-term effect of acupuncture on these factors using a randomized control double-blind design., Methods: A total of 72 patients were randomized into 2 groups: treatment group (press tack acupuncture) and control group (press tack placebo). The face rating scale, numerical rating scale (NRS), portable incentive spirometer and Verran Snyder-Halpern sleep scale were measured at baseline, immediately after the intervention, and at the 4th day, with 2-weeks and 3-months follow-ups., Results: There were no significant changes between the groups at the baseline measurements, with the exception of hypertension comorbidity. Immediately after the intervention and on the 4th day follow-up, the patients in the treatment group showed a significantly lower face rating scale when compared to the control (P < 0.05). There were no significant changes in any of the other measurements between the groups (P > 0.05). Subgroup analysis revealed that the NRS for turn over on the 4th day was reduced significantly in the treatment group of patients without lung contusion (P < 0.05). For patients without pleural drainage, cough NRS in the treatment group was significantly reduced in the 2-week follow-up (P < 0.05)., Conclusions: This study showed that press tack acupuncture effects on pain reduction were inconclusive. However, future studies on the effect of acupuncture on blunt chest trauma patients are needed., Clinical Trial Registration: clinicaltirl.gov: NCT04318496., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Hypoxia and angiogenesis play key roles in the pathogenesis of esophageal squamous cell carcinoma (ESCC), but regulators linking these two pathways to drive tumor progression remain elusive. Here we provide evidence of ADAM9's novel function in ESCC progression. Increasing expression of ADAM9 was correlated with poor clinical outcomes in ESCC patients. Suppression of ADAM9 function diminished ESCC cell migration and in vivo metastasis in ESCC xenograft mouse models. Using cellular fractionation and imaging, we found a fraction of ADAM9 was present in the nucleus and was uniquely associated with gene loci known to be linked to the angiogenesis pathway demonstrated by genome-wide ChIP-seq. Mechanistically, nuclear ADAM9, triggered by hypoxia-induced translocation, functions as a transcriptional repressor by binding to promoters of genes involved in the negative regulation of angiogenesis, and thereby promotes tumor angiogenesis in plasminogen/plasmin pathway. Moreover, ADAM9 suppresses plasminogen activator inhibitor-1 gene transcription by interacting with its transcription factors at the promoter. Our findings uncover a novel regulatory mechanism of ADAM9 as a transcriptional regulator in angiogenesis and highlight ADAM9 as a promising therapeutic target for ESCC treatment., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Introduction: Blunt chest trauma (BCT) accounts for up to 65% of polytrauma patients. In patients with 0 to 2 rib fractures, treatment interventions are typically limited to oral analgesics and breathing exercises. Patients suffering from BCT experience symptoms of severe pain, poor sleep, and inability to perform simple daily life activities for an extended period of time thereafter. In this trial, we aim to investigate the efficacy of acupuncture as a functional and reliable treatment option for blunt chest trauma patients., Methods: The study is designed as a double-blind randomized control trial. We will include 72 patients divided into 2 groups; the acupuncture group (Acu) and placebo group (Con). The acupuncture group will receive true acupuncture using a uniquely designed press tack needle. The control group will receive placebo acupuncture treatment through the use of a similarly designed press tack needle without the needle element. The acupoints selected for both groups are GB 34, GB 36, LI 4, LU 7, ST 36, and TH 5. Both groups will receive 1 treatment only following the initial visit to the medical facility and upon diagnosis of BCT. Patient outcome measurements include: Numerical Rating Scale, Face Rating Scale, respiratory function flowmeter, Verran Snyder-Halpern sleep scale, and the total amount of allopathic medication used. Follow-up time will be scheduled at 4 days, 2 weeks, and lastly 3 months., Expected Outcome: The results of this study can potentially provide a simple and cost-effective analgesic solution to blunt chest trauma patients. This novel study design can serve as supporting evidence for future double-blind studies within the field of acupuncture., Other Information: The study will be conducted in the thoracic surgical department and acupuncture department in China Medical University Hospital, Taichung, Taiwan. The study will be conducted on blunt chest trauma patients and is anticipated to have minimum risk of adverse events. Enrollment of the patients and data collection will start from March 2020. Study completion time is expected in March 2022., Protocol Registration: (CMUH109-REC1-002), (NCT04318496)., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Tumor recurrence is an important issue for patients with stage I non-small cell lung cancer (NSCLC) and adjuvant therapy is considered of no benefit to a tumor less than 4 cm. The purpose of this study was to evaluate the impact of positron emission tomography/computed tomography (PET/CT) on tumor recurrence in patients with a completely resected pN0 NSCLC less than 4 cm., Methods: Between January 2011 and December 2016, 211 consecutive patients with diagnoses of stage I NSCLC less than 4 cm after complete resection were included. The maximum of standard uptake value (SUVmax) of primary tumor and the presence of positive lymph nodes on PET/CT scans were documented. Disease-free survival was evaluated by the Kaplan-Meier method and recurrence risk factors were identified by univariable and multivariable analyses., Results: Patients with positive lymph nodes on PET/CT had a lower 5-year disease-free survival (37.6% vs 72.7%, p < 0.001). Multivariable analysis demonstrated that the tumor SUVmax >2.93, the presence of positive lymph nodes on PET/CT, and poor differentiation were significant factors for tumor recurrence. Patients with the tumor SUVmax >2.93 and positive lymph nodes on PET/CT simultaneously had 5.33-fold increase in the risk of recurrence (p < 0.001)., Conclusion: The presence of positive lymph nodes on PET/CT scans can be a good indicator in predicting patients with high risk of developing recurrence in pN0 NSCLC less than 4 cm. This result helps identify patients likely to benefit from adjuvant therapy., Competing Interests: Declaration of competing interest All authors have no conflict of interest to disclose with respect to this study., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Metastasis is a crucial hallmark of cancer progression and remains the primary cause of patient deaths. Metastasis-associated proteases contribute to cancer progression by disrupting the extracellular matrix interaction to facilitate the spreading of cancer cells to other organs. ADAM9, a type of metalloprotease, has been reported to promote tumor biology and is associated with clinicopathological features such as poor outcome, therapy resistance, and metastasis formation. Targeting ADAM9 might serve as a putative therapeutic application; however, this option is currently unavailable. Resveratrol, a polyphenol from plants, has been shown to be promising for cancer treatment due to its wide variety of biological effects with few side effects. In this study, we demonstrated that resveratrol inhibits cancer cell migration and viability in lung and esophageal cancer cells through the regulation of ADAM9. Mechanistically, resveratrol inhibits ADAM9 protein expression in cancer cells through the ubiquitin-proteasome pathway. Moreover, resveratrol provides synergistic anticancer effects when combined with clinical chemotherapeutics. Our data suggests that resveratrol may inhibit human lung cancer and ESCC progression by inhibiting ADAM9 expression, thus providing a potential mechanism for the anticancer action of resveratrol., Competing Interests: None., (AJCR Copyright © 2020.)

Rationale: Brain metastasis in patients with lung cancer is life-threatening. However, the molecular mechanism for this catastrophic disease remains elusive, and few druggable targets are available. Therefore, this study aimed to identify and characterize proteins that could be used as therapeutic targets. Methods: Proteomic analyses were conducted to identify differentially expressed membrane proteins between brain metastatic lung cancer cells and primary lung cancer cells. A neuronal growth-associated protein, brain acid soluble protein 1 (BASP1), was chosen for further investigation. The clinical relevance of BASP1 in lung adenocarcinoma was first assessed. Tyrosine kinase activity assays and in vitro and in vivo functional assays were conducted to explore the oncogenic mechanisms of BASP1. Results: The protein levels of BASP1 were positively associated with tumor progression and poor prognosis in patients with lung adenocarcinoma. Membrane-bound BASP1 increased EGFR signaling and stabilized EGFR proteins by facilitating their escape from the ubiquitin-proteasome pathway. Reciprocally, activation of EGFR recruited more BASP1 to the plasma membrane, generating a positive feedback loop between BASP1 and EGFR. Moreover, the synergistic therapeutic effects of EGFR tyrosine kinase inhibitor and arsenic trioxide led to a reduction in the level of BASP1 protein observed in lung cancer cells with acquired resistance to EGFR inhibitors. Conclusions: The reciprocal interaction between BASP1 and EGFR facilitates EGFR signaling in brain metastatic lung cancer. Targeting the newly identified BASP1-EGFR interaction could open new venues for lung cancer treatment., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: For advanced esophageal cancer, the clinical significance of pretreatment nodal status (cN) as determined by different examinations remains unclear., Patients and Methods: Patients with esophageal squamous cell carcinoma who underwent neoadjuvant chemoradiation and surgery were analyzed in this study. Pretreatment cN status assessed by CT, EUS, and PET/CT and clinicopathological features were used to evaluate tumor recurrence and long-term survival., Results: Two hundred and twenty-two patients were identified in this study. Pretreatment PET/CT cN0 [odds ratio (OR) cN0 versus cN+, 5.316, p < 0.001] and pretreatment CT cN0 (OR 1.957, p = 0.032) both independently predicted ypN0. Pretreatment PET/CT cN0 was also associated with a lower recurrence rate and longer survival across the entire study group. Among patients with ypN0, pretreatment PET/CT cN+ indicated poor disease-free survival [hazard ratio (HR) 2.777, p = 0.001] and overall survival (HR 2.211, p = 0.034) compared with pretreatment PET/CT cN0, which predicted a favorable prognosis., Conclusions: Data from the current study suggest that pretreatment lymph node status as assessed by PET/CT is strongly correlated with survival outcomes after neoadjuvant chemoradiation and surgery in patients with esophageal squamous cell carcinoma. ypN0 patients can achieve better survival outcomes when pretreatment cN0 is assessed by PET/CT.

Cigarette smoking (CS) is common in asthma, aggravating inflammatory reactions. However, the current treatment strategies for asthma are still not effective enough, and novel therapeutic approaches are required for CS-induced asthmatic disorders. We here investigated the ability of CpG oligodeoxynucleotides (CpG-ODNs) to inhibit airway inflammation and remodeling in ovalbumin (OVA)-associated asthma in mice exposed to chronic CS, revealing potential mechanistic insights. Lung tissue specimens were histologically analyzed. Th1/Th2/Th17 associated cytokines in serum, bronchoalveolar lavage fluid (BALF), and lung specimens were quantitated by ELISA, qRT-PCR and immunoblot. Parameters of bone marrow-derived dendritic cells (BMDCs) functions were evaluated as well. The results showed that BALB/c mice after CS and OVA treatments developed an asthmatic phenotype with airway inflammation involving both eosinophils and neutrophils, goblet cell metaplasia, airway remodeling, and elevated OVA-specific serum IgE, serum IL-17A, and BALF Th17/Th2 associated cytokines. CpG-ODNs and budesonide were found to synergistically inhibit inflammatory cell recruitment in the lung, airway remodeling, IgE synthesis, and Th17/Th2 associated cytokines. Mechanistically, CpG-ODNs and budesonide acted synergistically on BMDCs via downregulation of TSLP receptor (TSLPR) and IL-23 production, and subsequently contributed to dampen Th17/Th2 polarization in CS-associated asthma. In conclusion, combined administration of CpG-ODNs and budesonide, in a synergistic manner, inhibits airway inflammation, and tissue remodeling mediated by BMDCs by regulating IL-23 secretion and blocking TSLP signaling, which subsequently contribute to alleviate Th17/Th2 imbalance in CS-associated asthma., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Image-guided radiotherapy (IGRT) is an advanced radiotherapy technique to improve the accuracy of treatment delivery. However, a recent randomized controlled trial (RCT) for prostate cancer patients treated with radiotherapy either via IGRT or routine care (no daily IGRT) reported a statistically significant worse overall survival for those treated with IGRT. This raised the concern regarding the effectiveness of IGRT for definitive concurrent chemoradiotherapy (dCCRT) for locally advanced esophageal squamous cell carcinoma (LA-ESqCC)., Methods: Eligible LA-ESqCC patients diagnosed between 2011 and 2015 were identified via the Taiwan Cancer Registry. We estimated propensity scores to construct a 1:1 propensity-score-matched groups and balance observable potential confounders. The hazard ratio (HR) of death as well as other outcomes was compared between IGRT and non-IGRT matched groups during the entire follow-up period. The impact of additional covariables was considered in the sensitivity analysis., Results: Our study population included 590 patients in the primary analysis. The HR for death when IGRT was compared with non-IGRT was 0.92 (95% confidence interval 0.77-1.10, P = 0.35). There were also no significant differences for other outcomes or sensitivity analyses., Conclusions: In this updated nonrandomized study using real world data, we found that the overall survival of LA-ESqCC patients treated with dCCRT was not statistically different between those treated with IGRT versus those without IGRT, although the hazard ratio was less than unity, ie, in favor of IGRT. The results should be interpreted with caution given the nonrandomized design and RCTs are needed to clarify our findings., Key Points: Significant findings of the study: The OS of LA-ESqCC patients treated with dCCRT was not statistically different between those treated with IGRT versus those without IGRT, although the hazard ratio was less than unity, ie, in favor of IGRT., What This Study Adds: In this updated nonrandomized study using real world data with additional potential confounders, our study provided a reasonable tentative evidence of lack of RCT as suggested in the literature., (© 2019 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

The experimental model of combined allergic rhinitis and asthma syndrome (CARAS) has shown that CpG oligodeoxynucleotides (CpG-ODNs) are potential inhibitors of type 2 helper cell-driven inflammatory responses. Currently available CpG-ODNs modestly inhibit allergic responses in CARAS, while a combination strategy for upper airway treatment by co-administration of CpG-ODNs and glucocorticoids may show good efficacy. This study aimed to assess the therapeutic effects of CpG-ODNs combined with budesonide (BUD) on upper and lower-airway inflammation and remodeling in mice with CARAS induced by chronic exposure to ovalbumin (OVA), exploring the possible underlying molecular mechanisms. A BALB/c mouse model of chronic CARAS was established by systemic sensitization and repeated challenge with OVA. Treatment with CpG-ODNs or BUD by intranasal administration was started 1 h after OVA challenge. Then, nasal mucosa and lung tissues were fixed and stained for pathologic analysis. The resulting immunologic variables and TSLP-DC-OX40L axis parameters were evaluated. Both CpG-ODNs and BUD intranasal administration are effective on reducing Th2-type airway inflammation and tissue remodeling. Co-administration of CpG-ODNs and BUD was more effective than each monotherapy in attenuating upper and lower-airway inflammation as well as airway remodeling in chronic CARAS. Notably, combination of CpG-ODNs with BUD modulated the TSLP-DC-OX40L axis, as demonstrated by decreased TSLP production in the nose and lung, alongside decreased TSLPR and OX40L in DC. Intranasal co-administration of CpG-ODNs and BUD synergistically alleviates airway inflammation and tissue remodeling in experimental chronic CARAS, through shared cellular pathways, as a potent antagonist of the TSLP-DC-OX40L axis.

Lung cancer has a very high prevalence of brain metastasis, which results in a poor clinical outcome. Up-regulation of a disintegrin and metalloproteinase 9 (ADAM9) in lung cancer cells is correlated with metastasis to the brain. However, the molecular mechanism underlying this correlation remains to be elucidated. Since angiogenesis is an essential step for brain metastasis, microarray experiments were used to explore ADAM9-regulated genes that function in vascular remodeling. The results showed that the expression levels of vascular endothelial growth factor A (VEGFA), angiopoietin-2 (ANGPT2), and tissue plasminogen activator (PLAT) were suppressed in ADAM9-silenced cells, which in turn leads to decreases in angiogenesis, vascular remodeling, and tumor growth in vivo. Furthermore, simultaneous high expression of ADAM9 and VEGFA or of ADAM9 and ANGPT2 was correlated with poor prognosis in a clinical dataset. These findings suggest that ADAM9 promotes tumorigenesis through vascular remodeling, particularly by increasing the function of VEGFA, ANGPT2, and PLAT.

MicroRNAs (miRNAs), which are endogenous short noncoding RNAs, can regulate genes involved in important biological and pathological functions. Therefore, dysregulation of miRNAs plays a critical role in cancer progression. However, whether the aberrant expression of miRNAs is regulated by oncogenes remains unclear. We previously demonstrated that a disintegrin and metalloprotease domain 9 (ADAM9) promotes lung metastasis by enhancing the expression of a pro-migratory protein, CUB domain containing protein 1 (CDCP1). In this study, we found that this process occurred via miR-1 down-regulation. miR-1 expression was down-regulated in lung tumors, but increased in ADAM9-knockdown lung cancer cells, and was negatively correlated with CDCP1 expression as well as the migration ability of lung cancer cells. Luciferase-based reporter assays showed that miR-1 directly bound to the 3'-untranslated region of CDCP1 and inhibited its translation. Treatment with a miR-1 inhibitor restored CDCP1 protein levels and enhanced tumor cell mobility. Overexpression of miR-1 decreased tumor metastases and increased the survival rate in mice. ADAM9 knockdown reduced EGFR signaling and increased miR-1 expression. These results revealed that ADAM9 down-regulates miR-1 via activating EGFR signaling pathways, which in turn enhances CDCP1 expression to promote lung cancer progression.

Purpose: To evaluate the outcomes of patients who underwent thoracoscopic wedge resection without chest drain placement., Methods: The subjects of this retrospective study were 89 patients, who underwent thoracoscopic wedge resection at our hospital between January, 2013 and July, 2015. A total of 45 patients whose underlying condition did not meet the following criteria were assigned to the "chest drain placement group" (group A): peripheral lesions, healthy lung parenchyma, no intraoperative air leaks, hemorrhage or effusion accumulation, and no pleural adhesion. The other 44 patients whose underlying condition met the criteria were assigned to the "no chest drain placement group" (group B). Patient characteristics, specimen data, and postoperative conditions were analyzed and compared between the groups., Results: Group A patients had poorer forced expiratory volume in one second (FEV1) values, less normal spirometric results, significantly higher resected lung volume, a greater maximum tumor-pleura distance, and a larger maximum tumor size. They also had a longer postoperative hospital stay. There was no difference between the two groups in postoperative complications., Conclusions: Avoiding chest drain placement after a thoracoscopic wedge resection appears to be safe and beneficial for patients who have small peripheral lesions and healthy lung parenchyma.

Liver transplant is now considered to be a successful treatment modality for early hepatocellular carcinoma. In addition, advances in immunosuppressive therapy have greatly prolonged posttransplant survival of patients with hepatocellular carcinoma. However, both the posttransplant physiologic condition and immunosuppressive therapy affect the patient's natural immunity, resulting in accumulating and more problematic complications. Three years after a male patient with hepatocellular carcinoma underwent living-donor liver transplant, he presented with esophageal metastasis from recurrence of hepatocellular carcinoma. This is an extremely rare complication, perhaps with an ominous prognosis, and, to the best of our knowledge, the first such case to be published in the English literature.

Metastasis is the leading cause of death in cancer patients due to the difficulty of controlling this complex process. MicroRNAs (miRNA), endogenous noncoding short RNAs with important biological and pathological functions, may play a regulatory role during cancer metastasis, but this role has yet to be fully defined. We previously demonstrated that ADAM9 enhanced the expression of the pro-migratory protein CDCP1 to promote lung metastasis; however, the regulatory process remains unknown. Here we demonstrate that endogenous miR-218, which is abundant in normal lung tissue but suppressed in lung tumors, is regulated during the process of ADAM9-mediated CDCP1 expression. Suppression of miR-218 was associated with high migration ability in lung cancer cells. Direct interaction between miR-218 and the 3'-UTR of CDCP1 mRNAs was detected in luciferase-based transcription reporter assays. CDCP1 protein levels decreased as expression levels of miR-218 increased, and increased in cells treated with miR-218 antagomirs. Induction of miR-218 inhibited tumor cell mobility, anchorage-free survival, and tumor-initiating cell formation in vitro and delayed tumor metastases in mice. Our findings revealed an integrative tumor suppressor function of miR-218 in lung carcinogenesis and metastasis.

Background: Video-assisted thoracoscopic surgery (VATS) is a minimally invasive alternative to conventional surgery (CS). We aimed to estimate the short-term cost-effectiveness of VATS vs. CS for clinical stage I non-small cell lung cancer (NSCLC-c-stage-I) patients from the payer's perspective (National Health Insurance)., Methods: We identified NSCLC-c-stage-I patients diagnosed and received surgery within 2007-2009 through a comprehensive population-based database containing cancer and death registries, and reimbursement data. The duration of interest was 1 year. We included potential confounding covariables through literature searching and our own experience, and used a propensity score to construct a 1:1 population for adjustment., Results: Our study population constituted 966 patients. The mean hospital stay [days, standard deviation (SD)] were 14.4 [7] and 16.1 (7.7) for VATS and CS respectively (P=0.002). The mean cost (2013 USD) and survival (year) was $22,316 vs. $21,976 and 0.98 vs. 0.974 for VATS vs. CS. The probability for VATS to be cost-effective (i.e., positive net benefit) was 0.49 & 0.56 at willingness-to-pay (WTP) 50,000 & 100,000 USD/life-year, respectively., Conclusions: We provide the first empirical evidence that when compared to CS, VATS was potentially cost-effective in the short term (1 year) within the common WTP levels in Taiwan.

Background: Thoracic endovascular aortic repair (TEVAR) is becoming increasingly popular due to reduced perioperative morbidity and mortality compared with open surgical repair. However, complications can occur when the left subclavian artery is involved. When performing TEVAR with left carotid-subclavian artery bypass the stent graft will extend to the left common carotid artery. We herein present the case of a patient with a type B aortic dissection with an acute intramural hematoma. Chylothorax was noted after TEVAR with left carotid-subclavian artery bypass., Case Report: A 66-year-old female with descending aortic dissection that was treated conservatively developed the sudden onset of back pain. Aortic computed tomography (CT) showed a type B intramural aortic dissection. TEVAR with left carotid-subclavian artery bypass was performed. Left chylothorax was noted after surgery with drainage of up to 1000 mL per day. Conservative management was ineffective. Thoracoscopic ligation of the thoracic duct was performed with resolution of the chyle leakage., Conclusion: Chylothorax can occur after TEVAR with carotid-subclavian artery bypass and likely results from thoracic duct injury. When conservative treatments fail, ligation of the thoracic duct cephalad to aortic hiatus can resolve the chyle leakage.

Background: Although blebs and bullae are frequently found in the apexes of lungs of patients with primary spontaneous pneumothorax (PSP), its pathogens remain unclear., Objectives: To examine the role of proteases [matrix metalloproteinase (MMP)-2, MMP-7 and MMP-9] and antiproteases [tissue inhibitors of metalloproteinase (TIMP)-1, TIMP-2, TIMP-3 and TIMP-4] in the pathogenesis of PSP., Method: Fifty consecutive PSP patients who received standard surgical care were enrolled in the study. Lung tissues from 20 patients with stage I non-small cell lung cancer were used as a control. Immunohistochemistry (IHC), reverse transcription-polymerase chain reaction (RT-PCR) and gelatin zymography were used to evaluate the expression of MMP and TIMP in the lung tissue of patients with PSP., Results: Overexpression of MMP-2, MMP-7 and MMP-9 was found in the afflicted lung by IHC, zymography and RT-PCR. By IHC, higher expression of MMP-2 and MMP-9 in PSP patients was identified in alveolar macrophages and type II pneumocytes (88 and 92% of patients in macrophages, and 72 and 70% of patients in type II pneumocytes, respectively). MMP-2, MMP-7 and MMP-9 expression in patients was higher in mesothelial cells (66, 76 and 76%). Overexpression of TIMP-2 was detected in the extracellular matrix around bullae and blebs. Expression levels of TIMP-1, TIMP-3 and TIMP-4 were negligible (<10% of cells) in both PSP patients and controls., Conclusions: MMP-2, MMP-9, MMP-7 and TIMP-2 were upregulated in PSP lesions. These results suggest that an imbalance between the expression of proteases and antiproteases may be involved in the pathogeneses of PSP., (© 2014 S. Karger AG, Basel.)

Objective: Single-incision laparoscopic surgery had been proven effective for appendectomy, cholecystectomy, and inguinal hernia repair. However, single-incision thoracoscopic surgery (SITS) in primary spontaneous pneumothorax (PSP) has not been reported., Methods: We prospectively enrolled 30 PSP patients who received thoracoscopic surgery in the division of Thoracic Surgery of China Medical University Hospital. Ten patients received SITS and 20 patients received traditional three-port thoracoscopic surgery. The operative time, blood loss, wound size, visual analog scale (VAS) pain score, and patient satisfaction score were compared., Results: There was no significant difference in the operative time and blood loss between the two groups. However, the VAS pain scores were significantly better in the SITS group in first 24 hours after surgery. Patient satisfaction scores in the SITS group were also significantly better in the first 24 and 48 hours after operation., Conclusion: Although three-port thoracoscopic surgery for PSP is well established, SITS results in better patient satisfaction and decreased postoperative pain in the treatment of PSP.

A 45-year-old man presented with a six-month history of progressive dyspnea with productive cough and wheezing. The patient was a heavy smoker and had a history of tongue cancer, hypertension, and asthma. Chest X-ray and computed tomography showed a mass lesion in the left hilar region and total collapse of the upper left lobe of the lung. Bronchoscopy revealed a whitish solid tumor obstructing the left upper lobe bronchus. Positron emission tomography showed increased tracer uptake in the lesion. A thoracoscopic lobectomy of the left upper lobe of the lung was performed. The final pathologic diagnosis was inflammatory myofibroblastic tumor.

Carcinosarcoma of the esophagus is a rare malignant neoplasm. It often presents as a large intraluminal polypoid tumor with early onset of symptoms resulting in prompt diagnosis. We present here the first case of a carcinosarcoma of the esophagus that had a basaloid squamous cell carcinoma component in addition to the osteosarcoma and without a transitional zone. A 57-year-old man was diagnosed with a polypoid tumor in middle third of the esophagus causing dysphagia. Local recurrence and solitary pulmonary metastasis occurred 16 and 30 months after initial excision of the tumor, respectively. Prompt and aggressive surgical resection is mandatory for carcinosarcoma of the esophagus.

Objective: We sought to determine whether Charlson comorbidity index (CCI) or Kaplan-Feinstein index (KFI) is a better predictor of prognosis in patients with stage I NSCLC after surgical resection., Methods: A retrospective study of medical records of 426 patients with stage I lung cancer having complete surgical resection from 1995 to 2000 was performed. Data collected included age, gender, smoking history, resection type, pleural invasion status, and tumor type and size. Comorbidity score was determined using Charlson comorbidity index and Kaplan-Feinstein index. Both univariate and multivariate analyses were used to evaluate prognostic factors., Results: Three hundred and twenty-eight male (76.99%) and 98 female (23.01%) patients had a mean age of 67.07 years (range 19-88 years). Median duration of follow-up was 60.32 months. Total follow-up rate was 95.1%. Distribution of CCI score was: 0, 236 (55.40%); 1, 112 (26.29%); >or=2, 78 (18.31%). Overall KFI score was: none, 247 (57.98%); mild, 126 (29.58%); moderate, 43 (10.09%); and severe, 10 (2.35%). In univariate analyses, patients aged>or=65 years, male, smokers, CCI score>or=2, extensive resection and pathological stage IB cancer had poorer 5-year survival. In multivariate logistic regression analysis, age>or=65 years, pneumonectomy, CCI score>or=2, and stage IB cancer were independent prognostic factors for poorer 5-year survival., Conclusions: Patients with CCI>or=2 had higher perioperative mortality and death from non-cancer causes after surgery compared to patients with CCI<2. However, KFI score had no impact on operative mortality and non-cancer death during follow-up.

One medical center in southern Taiwan faced an outbreak of nosocomial Legionnaires' disease; a total of 81 suspected cases were detected during an 8-month period. Baseline environmental surveillance showed that 80% of the distal sites in intensive care units (ICUs) were positive for Legionella pneumophila. Superheat-and-flush was selected for hospital water supply disinfection because it required no special equipment, and it can be initiated expeditiously. We conducted 2 episodes of superheat-and-flush based on the published recommendations from the Department of Health, Taiwan; US Centers for Disease Control and Prevention; and American Society of Heating, Refrigerating, and Air-Conditioning Engineers. Both flushes failed to control colonization of Legionella in the hospital water supply. The rate of distal sites positive for Legionella in wards and ICUs was 14% and 66%, respectively, 10 days after the second flush. The effect of replacement of faucets and showerheads in ICUs appeared to be insignificant in colonization of Legionella. The application of superheat-and-flush for flush duration of 5 minutes was ineffective. Superheat-and-flush may not be economic for a large medical center because it could be costly and labor intensive.

Background and Purpose: The treatment of community-acquired pneumonia (CAP) is complicated by the growing threat of antimicrobial resistance and the tendency to rely on empirical therapy. This study investigated the etiologic agents of adult CAP in Taiwan and the susceptibility of Streptococcus pneumoniae isolates from these patients., Methods: A collaborative group was established in the emergency department to conduct a prospective study of the etiology of adult CAP. The etiologic agent was determined by a combination of microscopic, culture, serologic and antigen detection methods. Pneumococcal susceptibility testing was performed to determine the extent of penicillin resistance., Results: A total of 100 consecutive cases of mild to moderate adult CAP prior to the severe acute respiratory syndrome epidemic were enrolled. The etiologic agent was determined in 72% of cases. The 5 most common causative pathogens were S. pneumoniae (26%), Mycoplasma pneumoniae (20%), Chlamydia pneumoniae (13%), Haemophilus influenzae (9%), and Klebsiella pneumoniae (5%). Atypical pathogens accounted for 40% of CAP. Bacteremic pneumonia was diagnosed in 6.2% of cases. Co-infections with 2 or more pathogens were found in 16% of the cases. Among the 20 isolates of S. pneumoniae, 85% (17/20) were susceptible to penicillin, 3 (15%) were intermediate, and none were resistant to penicillin., Conclusion: S. pneumoniae, M. pneumoniae and C. pneumoniae were the 3 leading causes of mild to moderate CAP in Taiwan. This study indicates that penicillin-resistant S. pneumoniae play a very limited role in this condition in adults.

Copper-silver (Cu-Ag) ionization has effectively controlled Legionella spp. in the hot water systems of numerous hospitals. However, it was ineffective at controlling Legionella in one Ohio hospital despite the confirmation of adequate total concentrations of copper and silver ions. The pH of the water at this hospital was found to be 8.5 to 9.0. The purpose of this study was to investigate the impact of pH and other water quality parameters, including alkalinity (HCO3-), hardness (Ca2+ and Mg2+), and amount of dissolved organic carbon (DOC), on the control of Legionella by Cu-Ag ionization. Initial concentrations of Legionella and copper and silver ions used in batch experiments were 3 x 10(6) CFU/ml and 0.4 and 0.08 mg/liter, respectively. Changes in bicarbonate ion concentration (50, 100, and 150 mg/liter), water hardness (Ca2+ at 50 and 100 mg/liter; Mg2+ at 40 and 80 mg/liter), and level of DOC (0.5 and 2 mg/liter) had no significant impact on the efficacy of copper and silver ions in killing Legionella at a neutral pH. When the pH was elevated to 9 in these experiments, copper ions achieved only a 10-fold reduction in the number of Legionella organisms in 24 h, compared to a millionfold decrease at pH 7.0. Silver ions were able to achieve a millionfold reduction in 24 h at all ranges of water quality parameters tested. Precipitation of insoluble copper complexes was observed at a pH above 6.0. These results suggest that pH may be an important factor in the efficacy of copper-silver ionization in controlling Legionella in water systems.