Prognostic factors for resected non-small cell lung cancer in patients with type 2 diabetes mellitus.

BACKGROUND: For diabetic patients with lung cancer, blood glucose levels and medications such as metformin and statins may influence survival. OBJECTIVES: This study aimed to determine prognostic survival factors for diabetic patients with resected non-small cell lung cancer. PATIENTS AND METHODS: Between January 2005 and December 2013, 301 patients with type 2 diabetes mellitus who underwent curative resection for non-small cell lung cancer were identified and reviewed retrospectively. RESULTS: The median follow-up period was 48 months. In multivariate analysis for lung cancer-specific survival, older age, forced expiratory volume in 1 s (FEV1) <80% predicted, and advanced pathologic stage were significant negative prognostic factors; statin use was a positive prognostic factor (hazard ratio (HR), 0.468). In multivariate analysis for overall survival, male sex, older age, comorbidity index, and advanced pathologic stage were significant negative prognostic factors and proper glycemic control (HR, 0.621) and statin use (HR, 0.585) were positive prognostic factors. CONCLUSIONS: Proper glycemic control (glycated hemoglobin A1c <7%) is recommended for diabetic patients undergoing lung cancer operations. Further studies are required to elucidate associations between type 2 diabetes mellitus and antineoplastic effects of statins and to evaluate statins as a novel adjuvant treatment for lung cancer.

Subnormothermic ex vivo lung perfusion possibly protects against ischemia-reperfusion injury via the mTORC-HIF-1α pathway.

Background: Ex vivo lung perfusion (EVLP) is a useful technique for evaluating and repairing donor lungs for transplantation. However, studies examining the effects of perfusate temperature on graft function are limited. Thus, this study aimed to examine these effects during EVLP on ischemic-reperfusion injury in the donor lung. Methods: Twenty-four male Sprague-Dawley rats were randomly divided into three groups, as follows: no treatment (sham group, n=5), normothermic EVLP (37 °C, n=5), and subnormothermic EVLP (30 °C, n=5). Lung function analyses, including oxygen capacity (OC), compliance, and pulmonary vascular resistance (PVR), were performed hourly during EVLP. Further, after 4 h of EVLP, histological evaluation of the right lobe was performed using the lung injury severity (LIS) scale. The expression levels of inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and IL-18 were evaluated. Metabolomic analysis of left lung tissues was conducted using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS) after 4 h of EVLP in the EVLP groups and after 1 h of cold preservation in the sham group. Results: Compared with those in the normothermic group, in the subnormothermic group, functional parameters during EVLP and subsequent histologic results were significantly superior, expression levels of inflammatory cytokines such as TNF-α, IL-1ß, IL-6, and IL-18 were significantly lower, and glycolytic activity was significantly decreased. Furthermore, expression levels of mammalian target of rapamycin complex (mTORC), hypoxia-inducible factor (HIF) 1α, and nucleotide-binding domain, leucine-rich-containing family pyrin domain containing 3 (NLRP3) and its effector caspase-1 were significantly lower in the subnormothermic group than in the normothermic group. Conclusions: EVLP with subnormothermic perfusion improves lung graft function by reducing the expression of pro-inflammatory cytokines and glycolytic activity during EVLP. Additionally, EVLP can be a useful target for the improvement of graft function after transplantation.

IL-17 and IL-22 enhance skin inflammation by stimulating the secretion of IL-1ß by keratinocytes via the ROS-NLRP3-caspase-1 pathway.

BACKGROUND: The pathogenesis of inflammatory skin disease involves the release of cytokines from keratinocytes, and one of these, IL-1ß, has been previously implicated in inflammatory skin disease. T(h)17 cells, a subset of T(h) cells involved in autoimmunity and inflammation, possess IL-1ß receptors and secrete cytokines such as IL-17 and IL-22 in response to IL-1ß stimulation. A mutation in the inflammasome protein NLRP3 (NACHT, LRR and PYD domains-containing protein 3) causes excess production of IL-1ß, resulting in an augmentation of T(h)17-dominant pathology. METHODS: To determine the feedback effect, if any, of IL-17 and/or IL-22 on the secretion of IL-1ß from keratinocytes, we stimulated the human keratinocyte cell line HaCaT, as well as caspase-1-deficient mice, with IL-17 or IL-22. RESULTS: We found that treatment with IL-17 and IL-22 causes an increase in IL-1ß via the activation of NLRP3 by a process that involves the generation of reactive oxygen species. Moreover, skin inflammation induced by IL-17 and IL-22 was lower in caspase-1 knockout (KO) mice relative to that induced by IL-1ß treatment. Additionally, skin inflammation induced by the drug imiquimod was lower in caspase-1 KO mice than in wild-type mice. CONCLUSION: These results indicate that cytokines from T(h)17 cells may potentiate IL-1ß-mediated skin inflammation and result in phenotypic alterations of keratinocytes via a feedback mechanism.

Transient hyperthermia during ex vivo lung perfusion has no protective effect in rat model.

BACKGROUND: Although ex vivo lung perfusion (EVLP) is a useful technique for evaluating and repairing donor lungs for transplantation, EVLP itself can lead to inflammation in the lung. Heat shock proteins (HSPs) have anti-inflammatory effects and can reduce ischemic reperfusion injury in the donor's lungs after transplantation. In this study, the effects of transient hyperthermia during EVLP on the expression of HSPs and inflammatory pathways were examined. METHODS: Fifteen male Sprague-Dawley rats were randomly divided into three groups: sham (n = 5), normothermic EVLP (37 °C, n = 5), and transient hyperthermia during EVLP (42 °C, n = 5). Lung function analyses regarding PaO2/FiO2 ratio, compliance, and pulmonary vascular resistance were conducted. The expression levels of HSPs and inflammatory cytokines were also evaluated. The degree of lung injury was histopathologically evaluated. Transcriptome analysis was performed on lung tissues from the sham (n = 2), normothermic EVLP (n = 2), and heat stress-EVLP (n = 2) groups. RESULTS: There were no significant differences in functional or histological parameters between the three groups. The expression of HSPs had significantly increased, especially that of HSPs 40 and 60 in the heat stress EVLP group; this was consistent with the inflammatory response. Inflammatory cytokine levels were significantly higher during EVLP and intensified with transient hyperthermia. CONCLUSION: Transient hyperthermia during EVLP has no protective effect on the donor lung graft or activation of the inflammatory pathway at the gene level.

IL-33 induces Th17-mediated airway inflammation via mast cells in ovalbumin-challenged mice.

Allergic asthma is characterized by infiltration of eosinophils, elevated Th2 cytokine levels, airway hyperresponsiveness, and IgE. In addition to eosinophils, mast cells, and basophils, a variety of cytokines are also involved in the development of allergic asthma. The pivotal role of eosinophils in the progression of the disease has been a subject of controversy. To determine the role of eosinophils in the progression of airway inflammation, we sensitized and challenged BALB/c wild-type (WT) mice and eosinophil-deficient ΔdblGATA mice with ovalbumin (OVA) and analyzed different aspects of inflammation. We observed increased eosinophil levels and a Th2-dominant response in OVA-challenged WT mice. In contrast, eosinophil-deficient ΔdblGATA mice displayed an increased proportion of mast cells and a Th17-biased response following OVA inhalation. Notably, the levels of IL-33, an important cytokine responsible for Th2 immune deviation, were not different between WT and eosinophil-deficient mice. We also demonstrated that mast cells induced Th17-differentiation via IL-33/ST2 stimulation in vitro. These results indicate that eosinophils are not essential for the development of allergic asthma and that mast cells can skew the immune reaction predominantly toward Th17 responses via IL-33 stimulation.

Surgical Complications Affecting the Early and Late Survival Rates after Lung Transplantation.

Since the first lung transplantation in humans was performed in 1963, patient selection, standardized procurement, and surgical techniques have been developed and established for this procedure. However, despite these developments, surgical complications continue to be important factors influencing patient morbidity and mortality, and efforts should be made to decrease morbidity and improve survival rates by understanding, rapidly detecting, and appropriately treating surgical complications.

WITHDRAWN: Effect of Disease Type on Changes in Total Lung Volume After Lung Transplantation.

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Orientia tsutsugamushi induced endothelial cell activation via the NOD1-IL-32 pathway.

Orientia tsutsugamushi (OT), the causative agent of scrub typhus, is an obligate intracellular bacterium. In order to verify the inflammatory responses involved in the pathogenesis of scrub typhus, we assessed the cytokine profile of the human endothelial cell line, ECV304, after OT infection. We noted that CCL5, CCL17, IL-1alpha, IL-6, IL-8, IL-10, IL-15, TNF-alpha and TNF-beta were strongly induced in response to OT. Additionally, IL-32, the candidate modulator for the induction of IL-6 and IL-8, was increased significantly with OT infection and these increases coincided with NOD1 pathway activation. Thus, we hypothesized that NOD1 pathway and IL-32 might act on cytokine release in endothelial cells as a modulator of the inflammation caused by OT infection. NOD1 siRNA resulted in a reduction in IL-32 levels, and also reduced IL-1beta, IL-6, IL-8, and ICAM-1 expression in OT-infected ECV304 cells. These changes in IL-1beta, IL-6, IL-8, and ICAM-1 induced by NOD1 knockdown were reversed as the result of IL-32 treatment. This indicated that OT infection activated the NOD1 pathway followed by IL-32 secretion, thus resulting in the production and expression of IL-1beta, IL-6, IL-8, and ICAM-1. Therefore, IL-32 might perform a role upstream of the inflammatory reaction in endothelial cells of OT infection.

Impact of extended-criteria donor lungs according to preoperative recipient status and age in lung transplantation.

Background: Organ donor shortage remains as one of the limiting factors for lung transplantation. Given the increase in waiting time, preoperative condition has worsened and affects surgical outcomes. This study aimed to evaluate the immediate postoperative and long-term outcomes of lung transplantation in extended-criteria donor (ECD) lungs compared with standard-criteria donor (SCD) lungs. Methods: A total of 246 patients who had undergone double-lung transplantation during the study period were enrolled. SCD was defined based on the following characteristics age <55 years, <20 pack-years smoking history, and PaO2/fraction of O2 ratio >300 mmHg. Organ donors who do not fulfill these criteria were classified as ECD. Pre- and postoperative data for outcomes and survival data were analyzed. Results: ECD showed significant association with extracorporeal membrane oxygenation weaning in the operating room (hazard ratio [HR], 0.531; 95% confidence interval [CI], 0.291-0.970; P=0.039) considering recipient's age and status at operation. The ECD group showed comparable survival rate with the SCD group (HR, 1.413; 95% CI, 0.885-2.255; P=0.148), with adjustment of other factors. However, when the recipient had Korean Network for Organ Sharing (KONOS) status 0 at the time of transplantation (HR, 1.662; 95% CI, 1.025-2.568; P=0.039), G3 primary graft dysfunction at 72 hours after surgery (HR, 2.508; 95% CI, 1.416-4.440; P=0.002) was a risk factor that decreased survival. Conclusions: The outcome of ECD is not inferior to that of SCD. Therefore, ECD lung should be considered a potential donor organ following active donor management rather than a contraindication of transplantation in highly selected recipients.

Risk of Bronchial Dehiscence in Lung Transplant Recipients With Carbapenemase-producing Klebsiella.

BACKGROUND: Klebsiella pneumoniae is commonly isolated after lung transplantation. This study observed an increase in bronchial complications after an outbreak of Klebsiella pneumoniae carbapenemase-producing Klebsiella (KPC-KP). METHODS: The study enrolled 173 patients who had undergone bilateral lung transplantation between 2012 and 2018 to examine the association between bronchial complications after lung transplantation and KPC-KP. The KPC-KP group was defined as patients whose isolates from sputum or bronchoalveolar lavage fluid were positive for KPC-KP. The presence of bronchial complications was defined as a positive finding on bronchoscopy in accordance with the criteria of the International Society for Heart and Lung Transplantation. Risk factors for bronchial complications were analyzed. RESULTS: KPC-KP was identified in 29 patients (16.8%), and bronchial dehiscence was observed in 13 patients (7.5%). Smoking (odds ratio [OR], 5.690; 95% confidence interval [CI], 1.106- to 9.260; P = .037), the presence of KPC-KP (OR, 5.360; 95% CI, 1.380 to 20.810; P = .015), and bronchial necrosis (OR, 7.009; 95% CI, 1.811 to 27.124; P = .005) were associated with bronchial dehiscence in a multivariate logistic regression model. CONCLUSIONS: The presence of KPC-KP in lung-transplant recipients significantly increased the risk of bronchial dehiscence, independent of bronchial necrosis. Thus, patients with KPC-KP require greater surveillance and follow-up bronchoscopy, irrespective of the presence or absence of bronchial necrosis or the overall patient condition.

Stepwise flowchart for decision making on sublobar resection through the estimation of spread through air space in early stage lung cancer1.

OBJECTIVES: The sensitivity for tumor spread through air space (STAS), an independent risk factor for locoregional recurrence after sublobar resection for lung cancer, has been relatively low in frozen sections. We aimed to determine predictors with high negative predictive value for the presence of STAS and to provide the flowchart in combination with these predictors for the decision-making for sublobar resection. MATERIALS AND METHODS: Between July 2015 and December 2017, 387 patients who underwent surgery for non-small cell lung cancer (NSCLC) with pathologic findings of the total masses measuring ≤ 2 cm were enrolled. The lesions were divided into two groups according to presence of STAS. We compared the preoperative characteristics, operative data, and developed a flowchart for STAS prediction using receiver operator characteristic curve analysis and multivariable logistic regression. RESULTS: The STAS-positive group (N = 111) had a significantly higher preoperative tumor size (1.70 [1.5] vs 1.50 [0.69], p < 0.001) and standardized uptake value tumor-to-liver (SUV T/L) ratio (1.40 [1.60] vs 0.60 [1.10], p < 0.001) and a significantly lower two-dimensional ground-glass opacity (GGO) percentage (35.86 [61.00] vs 78.14 [39.00], p < 0.001). Meanwhile, the STAS-negative group (N = 286) had higher lepidic predominance (41.6% vs. 1.8%, p < 0.001). We developed a flowchart for predicting STAS in combination with two-dimensional GGO percentage on computed tomography (CT), SUV T/L ratio on positron-emission CT, and lepidic predominant pattern. The sensitivity, specificity, and negative predictive value for STAS positivity were 79.3%, 68.5%, and 89.5%, respectively. CONCLUSIONS: The stepwise flowchart using two-dimensional GGO percentage on CT, maximum SUV, and lepidic predominance might be helpful in selecting patients with early NSCLC for sublobar resection.

The Effect of Additional Stepwise Venous Inflow on Differential Hypoxia of Veno-Arterial Extracorporeal Membrane Oxygenation.

Use of femoral-femoral veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) for cardiopulmonary support during lung transplantation can be inadequate for efficient distribution of oxygenated blood into the coronary circulation. We hypothesized that creating a left-to-right shunt flow using veno-arterio-venous (VAV) ECMO would alleviate the differential hypoxia. Total 10 patients undergoing lung transplantation were enrolled in this study. An additional inflow cannula was inserted into the right internal jugular (RIJ) vein for VAV ECMO. During left one-lung ventilation using a 1.0 inspired oxygen fraction (FiO2), the left-to-right shunt flow was incrementally increased from 0 to 500, 1,000, and 1,500 ml/min. The arterial oxygen partial pressure (PaO2) and oxygen saturation (SaO2) were measured at the proximal ascending aorta and right radial artery. The ascending aorta gas analysis revealed that six patients had a PaO2/FiO2 ratio less than 200 mm Hg at a 0 ml/min shunt flow. The PaO2 (SaO2) values were 48.5 ± 14.8 mm Hg (80.9 ± 11.6%) at the ascending aorta and 77.8 ± 69.7 mm Hg (83.3 ± 13.2%) at the right radial artery. As the left-to-right shunt flow rate increased over 1,000 ml/min, the PaO2 and SaO2 values for the ascending aorta and right radial artery significantly increased. In conclusion, femoral-femoral VA ECMO can produce suboptimal coronary oxygenation in patients unable to tolerate one-lung ventilation. A left-to-right shunt using VAV ECMO can alleviate the differential hypoxia.

CSF total tau/α-synuclein ratio improved the diagnostic performance for Alzheimer's disease as an indicator of tau phosphorylation.

BACKGROUND: Recently, several studies suggested potential involvements of α-synuclein in Alzheimer's disease (AD) pathophysiology. Higher concentrations of α-synuclein were reported in cerebrospinal fluid (CSF) of AD patients with a positive correlation towards CSF tau, indicating its possible role in AD. We analyzed the CSF biomarkers to verify whether α-synuclein could be an additional supported biomarker in AD diagnosis. METHODS: In this cross-sectional study, CSF samples of 71 early-onset AD, 34 late-onset AD, 11 mild cognitive impairment, 17 subjective cognitive decline, 45 Parkinson's disease, and 32 healthy control (HC) were collected. CSF amyloid-ß1-42 (A), total tau (N), and phosphorylated tau181 (T) were measured by commercial ELISA kits, and in-house ELISA kit was developed to quantify α-synuclein. The cognitive assessments and amyloid-PET imaging were also performed. RESULTS: CSF α-synuclein manifested a tendency to increase in AD and to decreased in Parkinson's disease compared to HC. The equilibrium states of total tau and α-synuclein concentrations were changed significantly in AD, and the ratio of total tau/α-synuclein (N/αS) was dramatically increased in AD than HC. Remarkably, N/αS revealed a strong positive correlation with tau phosphorylation rate. Also, the combination of N/αS with amyloid-ß1-42/phosphorylated tau181 ratio had the best diagnosis performance (AUC = 0.956, sensitivity = 96%, specificity = 87%). In concordance analysis, N/αS showed the higher diagnostic agreement with amyloid-ß1-42 and amyloid-PET. Analysis of biomarker profiling with N/αS had distinctive characteristics and clustering of each group. Especially, among the group of suspected non-Alzheimer's disease pathophysiology, all A-T+N+ patients with N/αS+ were reintegrated into AD. CONCLUSIONS: The high correlation of α-synuclein with tau and the elevated N/αS in AD supported the involvement of α-synuclein in AD pathophysiology. Importantly, N/αS improved the diagnostic performance, confirming the needs of incorporating α-synuclein as a biomarker for neurodegenerative disorders. The incorporation of a biomarker group [N/αS] could contribute to provide better understanding and diagnosis of neurodegenerative disorders.

The role of postoperative radiotherapy in stage II and III thymoma: a Korean multicenter database study.

BACKGROUND: Complete resection is a standard treatment for patients with Masaoka-Koga stages II and III thymoma, however the role of postoperative radiotherapy (PORT) is controversial. We analyzed data collected from 4 Korean hospitals to determine the effectiveness of PORT in stage II and III thymoma patients. METHODS: Between January 2000 and December 2013, 1,663 patients underwent surgery for thymic tumors at the 4 hospitals. Among them, 668 patients (527 with stage II and 141 with stage III) were investigated, among whom, 443 received PORT (335 with stage II and 108 with stage III). Propensity score matching (PSM) was performed, and 404 patients (346 with stage II and 58 with stage III) were selected. RESULTS: Perioperative characteristics were similar in the PORT and non-PORT groups after PSM. On survival analysis of stage II patients, the PORT and non-PORT groups showed no difference in either 5-year recurrence-free survival (RFS) (96.3% vs. 96.6%, P=0.622) or 5-year overall survival (OS) (94.6% vs. 93.8%, P=0.839). However, among stage III patients, the PORT group showed significantly better 5-year RFS (75.7% vs. 50.1%, P=0.040) and 5-year OS (86.5% vs. 54.7%, P=0.001). On multivariate Cox regression analysis, PORT was a significant positive prognostic factor in terms of both RFS (P=0.005) and OS (P=0.004) in patients with stage III thymomas, but not in those with stage II disease (P=0.987 and 0.968, respectively). CONCLUSIONS: PORT improved the RFS and OS in stage III thymoma patients, but showed no survival benefit in stage II patients.

The lung allocation score could evaluate allocation systems in countries that do not use the score.

BACKGROUND: Evaluating allocation system effects on lung transplantation and determining systemic flaws is difficult. The purpose of this study was to assess the Korean urgency-based lung allocation system using the lung allocation score. METHODS: We reviewed transplantation patients retrospectively. Candidates were classified into groups based on urgency. Status 0 designated hospitalized patients requiring ventilator and/or extracorporeal life support. The lung allocation score was calculated based on the recipient's condition at transplantation. RESULTS: One-hundred-twenty-three Status 0, 1, and 2/3 patients (40, 71, and 12, respectively) were enrolled. The median waiting time was 68 days. Nineteen Status 0 patients who received lung transplants deteriorated from non-Status 0 (median, 64 days). The lung allocation score showed a bimodal distribution (peaks around 45 and 90, corresponding with non-Status 0 and Status 0, respectively). Status 0 and the lung allocation score were independent risk factors for poor survival after adjustment for confounders (Status 0, hazard ratio, 2.788, p = 0.001; lung allocation score, hazard ratio, 1.025, p < 0.001). The lung allocation score cut-off for survival was 44. On dividing the non-Status 0 patients into 2 groups using the cut-off values and regrouping into Status 0, non-Status 0 with high lung allocation score (> 44), and non-Status 0 with low lung allocation score (< 44), we observed that non-Status 0 with high lung allocation score patients had better survival than Status 0 patients (p = 0.020) and poorer survival than non-Status 0 with low lung allocation score patients (p = 0.018). CONCLUSIONS: The LAS demonstrated the characteristics of LTx recipients in Korea and the Korean allocation system needs to be revised to reduce the number of patients receiving LTx in Status 0. The LAS system could be used as a tool to evaluate lung allocation systems in countries that do not use the LAS system.

Feasibility and surgical outcomes of video-assisted thoracoscopic pulmonary resection in patients with advanced-stage lung cancer after neoadjuvant chemoradiotherapy.

Video-assisted thoracoscopic surgery (VATS) is regarded as the standard treatment for lung cancer. However, the feasibility and safety of VATS for lung cancer after neoadjuvant chemoradiotherapy (CRT) is unclear. This study evaluated the feasibility and safety of VATS in patients who had received neoadjuvant CRT. METHODS: Between January 2008 and December 2017, 85 patients who were administered neoadjuvant CRT and underwent anatomic lung resection were enrolled. Fifty-nine patients underwent open thoracotomy and 26 patients underwent VATS. The clinical characteristics and perioperative outcomes were reviewed. RESULTS: In six of the initial 32 patients who underwent VATS, the procedure was converted to thoracotomy. Adjacent structural invasion (33.9% vs. 11.5%; P = 0.037) and combined resection (16.9% vs. 0%; P = 0.025) were higher in the open group than in the VATS group. Surgical duration was higher in the open group than in the VATS group (203.86 ± 65.97 vs. 173.27 ± 59.87 minutes; P = 0.046). With regard to postoperative outcomes, the length of the hospital stay was longer in the open group compared to the VATS group (14.46 ± 16.94 vs. 8.62 ± 4.72 days; P = 0.017). There was no significant difference in the three-year disease-free survival (69.3% vs. 67.9%; P = 0.879) or overall survival rates (76.6% vs. 61.9%; P = 0.516). CONCLUSION: In selected patients, VATS pulmonary resection after neoadjuvant CRT showed results comparable to that of thoracotomy in terms of postoperative outcomes, operative morbidities, and survival rate.

Effect of Sarcopenic Overweight on Lung Transplant Based in Three-Dimensional Reconstructed Psoas Muscle Mass.

BACKGROUND: In lung transplantation, preoperative sarcopenia was reported to be associated with short-term outcomes based on cross-sectional image. This study aimed to investigate the influence of psoas muscle mass (PMM) on the operative outcome and survival using three-dimensional reconstruction of PMM and to evaluate the effect of preoperative sarcopenic overweight on postoperative outcomes and survival. METHODS: A total of 107 patients who underwent double lung transplantation in one institute from January 1, 2014, to June 30, 2017, were enrolled. The PMM was measured by Synapse 3D (Fujifilm, Seoul, Korea) visualization software based on computed tomography and three-dimensional reconstruction images. Patients were separated into two groups according to tercile of PMM (below the first tercile was defined as sarcopenia) and then subdivided according to PMM and overweight (body mass index ≥23 kg/m2). RESULTS: Sarcopenia had a significant relation with higher rate of postoperative tracheostomy (p = 0.040) and operative mortality (p = 0.023). For survival analysis, patients with sarcopenia showed a trend toward poorer outcome, but it was not significant (3-year survival rate 50.2% versus 73.2%, p = 0.054). Moreover, PMM was significantly associated with the length of mechanical ventilation (ß = -0.368, p = 0.047) and length of intensive care unit stay (ß = -0.372, p = 0.046). Sarcopenic overweight has no significant difference in terms of length of mechanical ventilation and length of intensive care unit. However, overall survival was significantly lower among patients with sarcopenic overweight than among those without sarcopenia (p = 0.026 and p = 0.024, respectively). CONCLUSIONS: Sarcopenia was associated with poorer short-term outcome, and sarcopenic overweight with poorer overall survival of lung transplant patients.

Neoadjuvant therapy for thymic neoplasms reduces tumor volume per 3D-reconstructed images but does not improve the complete resection rate.

OBJECTIVES: Complete resection of thymic neoplasms is important for achieving a favorable prognosis; however, the efficacy of neoadjuvant therapy remains controversial. We investigated the effect of induction therapy on complete resection and survival using 3-dimensionally reconstructed images to measure tumor volume. METHODS: Eighty-nine patients who underwent surgical resection for Masaoka-Koga stage III-IV thymic neoplasms between January 2000 and December 2013 were enrolled, including 71 and 18 in the primary surgery and neoadjuvant therapy groups, respectively. Baseline characteristics, postoperative outcomes, and survival rates were analyzed. Moreover, baseline and post-neoadjuvant therapy tumor volumes were compared among patients in the neoadjuvant group. RESULTS: Adjacent mediastinal structure invasion was significantly rarer in the primary surgery group than in the neoadjuvant group (1.27±1.09 vs. 2.61±1.42, p<0.001). On subgroup analysis of patients who underwent neoadjuvant therapy, tumor volumes decreased significantly from 206.08±132.32 cm3 to 81.25±71.24 cm3 post-therapy (p = 0.001). Interestingly, only the pre-neoadjuvant tumor volume was significantly associated with complete resection, while the post-neoadjuvant volume was not (p = 0.012 and p = 0.458, respectively). Moreover, despite significantly reduced tumor volumes, patients in the neoadjuvant therapy group did not exhibit significantly different R0 resection rates (odds ratio 1.490, p = 0.581) or overall survival (p = 0.285) compared to those in the primary surgery group. CONCLUSIONS: Neoadjuvant therapy does not significantly influence the R0 resection rate or overall survival relative to primary surgery. Nevertheless, it may by useful for patients planning surgical resection because it significantly reduces the presurgical tumor volume and extent of invasion.

Comparison of the 11th Japanese classification and the AJCC 7th and 8th staging systems in esophageal squamous cell carcinoma patients.

BACKGROUND: Although the American Joint Committee on Cancer (AJCC) staging system has been used worldwide for esophageal squamous cell carcinoma (ESCC), another staging system has been proposed by Japanese surgeons. The two systems have different lymph node maps, N staging, and stage grouping. This retrospective study compared the predictive ability of these two staging systems for survival. METHODS: We retrospectively reviewed records for 143 patients who underwent esophagectomy and mediastinal lymphadenectomy for ESCC from January 2006 to July 2015. Patients were staged by 7th, 8th AJCC stage and 11th Japanese classification. The concordance indexes (C-indexes) of these staging systems were compared. RESULTS: Mean age was 63.14±8.10 years with 131 (91.6%) men. Median follow-up was 47.73 (6.27-134.40) months. All patients received R0 resection. Recurrences developed in 30 (20.9%) patients. Both AJCC N staging and Japanese N staging well predicted disease-free survival (DFS) (P<0.001). Stage groupings of AJCC 7th and 8th and Japanese 11th classification also predicted DFS well (P<0.001). The c-index was 0.755 (95% CI, 0.650-0.860) for AJCC N staging and 0.734 (0.634-0.835) for Japanese N staging (P=0.11). The c-index was 0.813 (0.732-0.896) for AJCC 7th stage grouping, 0.805 (0.726-0.885) for AJCC 8th, and 0.837 (0.766-0.908) for Japanese stage grouping. The C-index for the Japanese stage grouping was slightly higher than for AJCC, but differences were not significant. CONCLUSIONS: Both N staging and stage grouping for the 11th Japanese classification and 7th and 8th AJCC staging for ESCC showed similar predictive power for DFS. Both systems could be applied in clinical situations.

Risk Factors for Weight Loss 1 Year After Esophagectomy and Gastric Pull-up for Esophageal Cancer.

BACKGROUND: Loss of body weight is regarded as a marker of malnutrition after esophagectomy. This study investigated changes in body weight and risk factors for weight loss after esophagectomy for esophageal cancer. METHODS: We retrospectively reviewed records of 181 patients who underwent esophagectomy and gastric pull-up from 2012 to June 2016. Patients with operative mortality and recurrences were excluded. Percent change in body weight was defined as change in body weight (%) = (1-year body weight - preoperative body weight) × 100/preoperative body weight. RESULTS: Mean age of patients was 62.98 ± 8.23 years with 164 men (90.6%). Mean preoperative body weight was 63.12 ± 9.42 kg, and body weight at 1 year was 56.04 ± 8.59 kg. Mean change in body weight was - 10.95 ± 7.50%, and 98 (54.1%) patients showed weight loss more than 10% compared to initial body weight. Univariable analysis showed that initial body weight, narrow gastric tube, thoracotomy, laparotomy, and postoperative vocal cord palsy (VCP) were related to more than 10% weight loss. Multivariable analysis showed that initial body weight (odds ratio [OR] = 1.041, p = 0.031) and postoperative VCP (OR = 2.772, p = 0.025) were adverse risk factors for weight loss 1 year after esophagectomy, whereas conduit type, route of reconstruction, postoperative complications, anastomotic complications, minimally invasive esophagectomy, and adjuvant therapy were not. CONCLUSIONS: Initial body weight and postoperative VCP were related to weight loss. Patients with VCP need additional nutritional monitoring and support.