Development of the semi-dry dot-blot method for intraoperative detecting micropapillary component in lung adenocarcinoma based on proteomics analysis.

BACKGROUND: Micropapillary (MIP) component was a major concern in determining surgical strategy in lung adenocarcinoma (LUAD). We sought to develop a novel method for detecting MIP component during surgery. METHODS: Differentially expressed proteins between MIP-positive and MIP-negative LUAD were identified through proteomics analysis. The semi-dry dot-blot (SDB) method which visualises the targeted protein was developed to detect MIP component. RESULTS: Cellular retinoic acid-binding protein 2 (CRABP2) was significantly upregulated in MIP-positive LUAD (P < 0.001), and the high CRABP2 expression zone showed spatial consistency with MIP component. CRABP2 expression was also associated with decreased recurrence-free survival (P < 0.001). In the prospective cohort, the accuracy and sensitivity of detecting MIP component using SDB method by visualising CRABP2 were 82.2% and 72.7%, which were comparable to these of pathologist. Pathologist with the aid of SDB method would improve greatly in diagnostic accuracy (86.4%) and sensitivity (78.2%). In patients with minor MIP component (≤5%), the sensitivity of SDB method (63.6%) was significantly higher than pathologist (45.4%). CONCLUSIONS: Intraoperative examination of CRABP2 using SDB method to detect MIP component reached comparable performance to pathologist, and SDB method had notable superiority than pathologist in detecting minor MIP component.

Clinical utility of [18F]FDG PET/CT in the assessment of mediastinal lymph node disease after neoadjuvant chemoimmunotherapy for non-small cell lung cancer.

OBJECTIVES: The performance of positron emission tomography/computed tomography (PET/CT) for the prediction of ypN2 disease in non-small cell lung cancer (NSCLC) after neoadjuvant chemoimmunotherapy has not been reported. This multicenter study investigated the utility of PET/CT to assess ypN2 disease in these patients. METHODS: A total of 181 consecutive patients (chemoimmunotherapy = 86, chemotherapy = 95) at four institutions were enrolled in this study. Every patient received a PET/CT scan prior to surgery and complete resection with systematic nodal dissection. The diagnostic performance was evaluated through area under the curve (AUC). Kaplan-Meier method and Cox analysis were performed to identify the risk factors affecting recurrences. RESULTS: The sensitivity, specificity, and accuracy of PET/CT for ypN2 diseases were 0.667, 0.835, and 0.779, respectively. Therefore, the AUC was 0.751. Compared with the false positive cases, the mean value of max standardized uptake value (SUVmax) (6.024 vs. 2.672, p < 0.001) of N2 nodes was significantly higher in true positive patients. Moreover, the SUVmax of true positive (7.671 vs. 5.976, p = 0.365) and false (2.433 vs. 2.339, p = 0.990) positive cases were similar between chemoimmunotherapy and chemotherapy, respectively. Survival analysis proved that pathologic N (ypN) 2 patients could be stratified by PET/CT-N2(+ vs. -) for both chemoimmunotherapy (p = 0.023) and chemotherapy (p = 0.010). CONCLUSIONS: PET/CT is an accurate and non-invasive test for mediastinal restaging of NSCLC patients who receive neoadjuvant chemoimmunotherapy. The ypN2 patients with PET/CT-N2( +) are identified as an independent prognostic factor compared with PET/CT-N2(-). CLINICAL RELEVANCE STATEMENT: Imaging with 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) plays an integral role during disease diagnosis, staging, and therapeutic response assessments in patients with NSCLC. PET/CT could be an effective non-invasive tool for predicting ypN2 diseases after neoadjuvant chemoimmunotherapy. KEY POINTS: • PET/CT could serve as an effective non-invasive tool for predicting ypN2 diseases. • The ypN2 patients with PET/CT-N2( +) were a strong and independent prognostic factor. • The application of PET/CT for restaging should be encouraged in clinical practice.

Gut-Lung Dysbiosis Accompanied by Diabetes Mellitus Leads to Pulmonary Fibrotic Change through the NF-κB Signaling Pathway.

Growing evidence shows that the lungs are an unavoidable target organ of diabetic complications. However, the pathologic mechanisms of diabetic lung injury are still controversial. This study demonstrated the dysbiosis of the gut and lung microbiome, pulmonary alveolar wall thickening, and fibrotic change in streptozotocin-induced diabetic mice and antibiotic-induced gut dysbiosis mice compared with controls. In both animal models, the NF-κB signaling pathway was activated in the lungs. Enhanced pulmonary alveolar well thickening and fibrotic change appeared in the lungs of transgenic mice expressing a constitutively active NF-κB mutant compared with wild type. When lincomycin hydrochloride-induced gut dysbiosis was ameliorated by fecal microbiota transplant, enhanced inflammatory response in the intestine and pulmonary fibrotic change in the lungs were significantly decreased compared with lincomycin hydrochloride-treated mice. Furthermore, the application of fecal microbiota transplant and baicalin could also redress the microbial dysbiosis of the gut and lungs in streptozotocin-induced diabetic mice. Taken together, these data suggest that multiple as yet undefined factors related to microbial dysbiosis of gut and lungs cause pulmonary fibrogenesis associated with diabetes mellitus through an NF-κB signaling pathway.

IL-17 Promotes Pseudomonas aeruginosa Keratitis in C57BL/6 Mouse Corneas.

The aim of this study was to elucidate the expression and functions of IL-17 in C57BL/6 mouse corneas in response to Pseudomonas aeruginosa infection. We found that P. aeruginosa infection induced and increased signaling of IL-23/23R/17/17R in mouse corneas. Targeting IL-17A or the IL-17A-specific receptor IL-17RA/IL-17RC with neutralizing Abs resulted in a significant decrease in the severity of P. aeruginosa keratitis, including a decrease in bacterial burden and polymorphonuclear leukocyte infiltration. IL-17A-signaling blockade also significantly reduced the expression of the proinflammatory cytokines L-1ß, IL-24, and MMP-13 and increased the expression of the anti-inflammatory cytokine IL-1RA in mouse corneal epithelium. The presence of mouse IL-17A exacerbated P. aeruginosa-mediated tissue destruction. A cytokine protein array revealed that the expression of osteoprotegerin (OPG) was regulated by IL-17A, and OPG neutralization also resulted in a decrease in the severity of P. aeruginosa keratitis. Although both IL-17 and OPG affected the balanced expression of IL-1ß and IL-1RA, only IL-17 inhibited the expression of TH2 cytokines. Taken together, our results revealed that IL-17A, along with its downstream factor OPG, plays a detrimental role in the pathogenesis of P. aeruginosa keratitis. Targeting IL-17A and/or the OPG/RANKL/RANK/TRAIL system is a potential therapeutic strategy in controlling the outcome of P. aeruginosa keratitis, which was demonstrated by concurrent topical application of IL-17A-neutralizing Ab and ciprofloxacin in B6 mice.

The role of aspirin dose and initiation time in the prevention of preeclampsia and corresponding complications: a meta-analysis of RCTs.

PURPOSE: To investigate the role of different dosages and initial times of aspirin in preeclampsia prevention. METHODS: This meta-analysis was performed based on randomized-control trials (RCTs). RCTs of women assigned to receive low-dose aspirin, placebo, or no treatment were included. Preeclampsia and corresponding complications were pooled for analysis. All studies were retrieved from PubMed, Embase, Cochrane and Web of Science. RESULTS: A total of 46 studies were obtained in this meta-analysis, which consisted of 24,028 participants. When women at ≤ 16 gestational weeks started treatment with a dosage of < 100 mg/day aspirin, there was a significant reduction in the incidence of preeclampsia (RR = 0.75; 95% CI 0.58-0.98; P = 0.03), while in the subgroup receiving ≥ 100 mg/day aspirin, the result was RR = 0.71 (95% CI 0.53-0.95; P = 0.02). When aspirin was initiated at > 16 weeks, with a dosage of < 100 mg/day aspirin, there was a lesser preventive effect (RR = 0.80; 95% Cl 0.64-1.00; P = 0.05), and there was no significance in the subgroup receiving ≥ 100 mg/day aspirin (RR = 0.76; 95% Cl 0.45-1.31; P = 0.32). Furthermore, aspirin was revealed to have a protective effect on reducing preterm delivery, but there was an increased risk of postpartum hemorrhage. No significant result was obtained for fetal loss. CONCLUSION: The results of this meta-analysis suggest that high-risk pregnant women can prevent preeclampsia or preterm delivery by taking low-dose aspirin; the most efficient period is ≤ 16 weeks of gestation, and the best dose is ≥ 100 mg.

Recognition of filigree pattern expands the concept of micropapillary subtype in patients with surgically resected lung adenocarcinoma.

Our study aimed to validate the clinicopathological characteristics and prognosis of lung adenocarcinoma (ADC) with a filigree pattern and to further investigate the relationship between the filigree pattern and the classical micropapillary (MP) pattern. We retrospectively reviewed the clinical and pathologic characteristics of 461 Chinese patients with completely resected ADC (stage I, 310; stage II, 44; stage III, 107). The filigree pattern was more likely to be observed in ADC with a higher stage (p = 0.003) and the classical MP pattern (p < 0.001). Patients with filigree-predominant ADC showed poor survival, similar to those with classical MP-predominant ADC. Multivariate analysis confirmed that the presence of the filigree pattern was an independent prognostic factor for recurrence-free survival (hazard ratio (HR), 2.01; 95% confidence interval (CI), 1.50-2.68; p < 0.001) and overall survival (OS; HR, 1.83; 95% CI, 1.34-2.50; p < 0.001). Patients with both classical MP-positive and filigree-positive ADC had the worst survival compared with those with the filigree pattern or classical MP pattern alone. In stage I, ADC with both the filigree and classical MP patterns had a higher incidence of micrometastasis than ADC with the filigree pattern or classical MP pattern alone. Lymph node micrometastasis indicated poor survival in patients with ADC with the filigree pattern or classical MP pattern. Similar clinicopathologic features between patients with the filigree pattern and the classical MP pattern support the inclusion of the filigree pattern in the MP category. Recognition of the filigree pattern could provide helpful prognostic information, especially for stage I ADC.

The cGAS-STING signaling pathway contributes to the inflammatory response and autophagy in Aspergillus fumigatus keratitis.

Fungal keratitis is a serious corneal infection, which can lead to significant visual impairment and blindness. The cGAS-STING signaling pathway has emerged as a key player in innate immunity by sensing of invading pathogens. However, the role of the cGAS-STING pathway in Aspergillus fumigatus (A. fumigatus) keratitis is still unknown. In this study, we showed that the cGAS-STING signaling pathway was activated in human corneal epithelial cells (HCECs) and in mouse corneas infected with A. fumigatus. Knockdown of cGAS reduced A. fumigatus-induced production of pro-inflammatory cytokines, including TNF-α, IL-1ß, IL-6, and IFN-ß. However, reconstruction of cGAS activity restored the inflammatory response in HCECs infected with A. fumigatus. A specific cGAS inhibitor, RU.521, could also significantly inhibit A. fumigatus-induced inflammatory cytokine expression. In addition, we found that cGAS was indispensable for the autophagy flux evoked by A. fumigatus infection. Moreover, inhibition of cGAS using siRNA or RU.521 alleviated the severity of A. fumigatus keratitis in the mouse cornea. Therefore, the cGAS-STING signaling pathway contributes to the progression of A. fumigatus keratitis and targeting this pathway may provide therapeutic potential.

Clinicopathological and prognostic analyses of 86 resected pulmonary lymphoepithelioma-like carcinomas.

BACKGROUND: Pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare subtype of primary lung cancer. The present study aims at investigating clinicopathological features and prognostic characteristics of the resected pulmonary LELC. METHODS: Patients with resected pulmonary LELC were identified in our hospital from December 2008 to December 2018. Data of these patients were retrospectively reviewed, clinicopathological features and prognostic characteristics were analyzed subsequently. RESULTS: In total, 86 patients were enrolled in the study, including 39 (45.3%) males and 47 (54.7%) females. Most of the serum tumor markers were normal. Immunohistochemical staining result showed frequent differentiation traits of epithelial tissue such. Positive PD-L1 (15 of 19, 78.9%) and PD-1 (13 of 17, 76.5%) were also common, but cancer-related genetic mutation was scarce (1 of 47, 2.1%). Survival analyses demonstrated that the N stage (p = .011) and extent of resection (p = .023) were identified as independent predictive factors for overall survival. CONCLUSIONS: Pulmonary LELC is a distinctive subtype of lung cancer with several exclusive traits, such as the trend to happen among nonsmoking young people, epithelial origin of tumor differentiation, frequent expression of the immune checkpoint, and scarce presence of driver mutation. In addition, pulmonary LELC was apt to get a favorable outcome, especially in cases diagnosed and treated in the early stage.

Opposing Effects of IL-1Ra and IL-36Ra on Innate Immune Response to Pseudomonas aeruginosa Infection in C57BL/6 Mouse Corneas.

Pseudomonas aeruginosa keratitis is characterized by severe corneal ulceration and may lead to blindness if not treated properly in a timely manner. Although the roles of the IL-1 subfamily of cytokines are well established, as a newly discovered subfamily, IL-36 cytokine regulation, immunological relevance, and relation with IL-1 cytokines in host defense remain largely unknown. In this study, we showed that P. aeruginosa infection induces the expression of IL-36α and IL-36γ, as well as IL-1ß and secreted IL-1Ra (sIL-1Ra), but not IL-36Ra. Downregulation of IL-1Ra increases, whereas downregulation of IL-36Ra decreases the severity of P. aeruginosa keratitis. IL-1R and IL-36Ra downregulation have opposing effects on the expression of IL-1ß, sIL-1Ra, IL-36γ, S100A8, and CXCL10 and on the infiltration of innate immune cells. Administration of recombinant IL-1Ra improved, whereas IL-36Ra worsened the outcome of P. aeruginosa keratitis. Local application of IL-36γ stimulated the expression of innate defense molecules S100A9, mouse ß-defensin 3, but suppressed IL-1ß expression in B6 mouse corneas. IL-36γ diminished the severity of P. aeruginosa keratitis, and its protective effects were abolished in the presence of S100A9 neutralizing Ab and partially affected by CXCL10 and CXCR3 neutralizations. Thus, our data reveal that IL-1Ra and IL-36Ra have opposing effects on the outcome of P. aeruginosa keratitis and suggest that IL-36 agonists may be used as an alternative therapeutic to IL-1ß-neutralizing reagents in controlling microbial keratitis and other mucosal infections.

Prognostic Impact of Tumor Spread Through Air Spaces in Sublobar Resection for 1A Lung Adenocarcinoma Patients.

BACKGROUND: This study aimed to clarify differences in the prognostic impact of tumor spread through air spaces (STAS) in lobectomy versus sublobar resection (SR). The study also investigated the frequency and significance of STAS in residual lung segments. METHODS: This study identified 752 patients with p-stage 1A non-small cell lung cancer (NSCLC) from 2010 to 2012. Recurrence-free survival (RFS) and overall survival (OS) were compared. For proactive simulation of SR, 100 consecutive lobectomy specimens of p-stage 1A NSCLC were selected. RESULTS: The study found STAS in 182 (28.7%) of 634 lobectomy cases and 43 (36.4%) of 118 SR cases. Multivariable analysis showed that STAS was not a prognostic factor in the lobectomy group, but showed a significantly worse prognostic effect for the SR group (RFS, P < 0.001; OS, P < 0.001). In 9 of 100 simulated cases, STAS occurred in residual lung segments. The patients with T1c category disease had a significantly increased risk for the development of STAS in residual lung segments (P = 0.033). CONCLUSIONS: For patients with p-stage 1A lung cancer who have undergone SR, STAS is a prognostic indicator of poor outcomes. The presence of STAS does occasionally exist in the residual lung segments.

Interactions of thymic stromal lymphopoietin with TLR2 and TLR4 regulate anti-fungal innate immunity in Aspergillus fumigatus-induced corneal infection.

Thymic stromal lymphopoietin (TSLP) is an interleukin 7 (IL-7)-like four helix bundle cytokine that plays diverse roles in the regulation of immune responses. In fungal infection, pattern recognition receptors (PRRs), including the cell surface Toll-like receptors (TLRs) and cytoplasmic NOD-like receptors, recognize pathogen-associated molecular patterns to initiate downstream signal cascades to active immune responses. Our previous studies reported that, in vitro human cornea epithelium cells represented a novel target of TSLP and that TSLP/TSLPR/STAT5 signaling played an important role in the response to Aspergillus fumigatus challenge. TSLP downstream signaling molecules upregulated TLR2 and MyD88/NF kappa B-p65 signaling. This phenomenon suggested that TSLP had an impact on PRRs in antifungal immunity. In mouse fungal keratitis induced by A. fumigatus, TSLP was mainly expressed in the epithelium as well as in some infiltrated immune cells in a time-dependent manner. Exogenous TSLP with Aspergillus led to severe keratitis and worse corneal recovery with higher levels of TLR2, TLR4, IL-6, and IL-8 as well as increased neutrophil infiltration. By contrast, when TSLP was suppressed by siRNA, fungal keratitis was mild with higher levels of antimicrobial peptides such as human beta-defensin (hBD9). Taken together, our data revealed an unreported function of TSLP in mediating an anti-fungal inflammatory response and serving as a target to control tissue injury and infection in A. fumigatus keratitis.

DOES T STAGE AFFECT PROGNOSIS IN PATIENTS WITH STAGE IV B DIFFERENTIATED THYROID CANCER?

Objective: Differentiated thyroid cancer (DTC), the most common subtype of thyroid cancer, has a relatively good prognosis. The 8th edition of the American Joint Committee on Cancer (AJCC) pathologic tumor-node-metastasis (T [primary tumor size], N [regional lymph nodes], M [distant metastasis]) staging system did not take the T stage into consideration in stage IV B DTC patients. We evaluated the prognostic value of the T stage for advanced DTC survival. Methods: DTC cases that were considered stage IV B in the AJCC 8th edition were extracted from the Surveillance, Epidemiology, and End Results database. T stage (AJCC 6th standard) was categorized into T0-2, T3 and T4. We analyzed overall survival (OS) and cancer specific survival (CSS) in the overall group as well as in pathologic subgroups. We used the Kaplan-Meier method and log-rank test for univariate analysis and the Cox regression model for multivariate analysis. Results: A total of 519 cases were extracted. Patients with earlier T stages showed significantly better OS and CSS in univariate analysis. T stage was an independent prognostic factor for both OS and CSS in multivariate analysis. Subgroup analysis in papillary and follicular thyroid cancer showed that T4 was an independent prognostic factor for both OS and CSS. Conclusion: AJCC 8 stage IV B DTC patients could be further stratified by T stage. Further studies with larger samples and AJCC 8 T stage information are necessary. Abbreviations: AJCC = American Joint Committee on Cancer; CI = confidence interval; CSS = cancer specific survival; DTC = differentiated thyroid cancer; FTC = follicular thyroid cancer; FVPTC = follicular variant of papillary thyroid carcinoma; HR = hazard ratio; OS = overall survival; PTC = papillary thyroid cancer; SEER = surveillance, epidemiology, and end results database.

Intraoperatively measured tumor size and frozen section results should be considered jointly to predict the final pathology for lung adenocarcinoma.

Invasive adenocarcinoma intraoperatively misdiagnosed as adenocarcinoma in situ or minimally invasive adenocarcinoma is more likely to undergo potentially insufficient resection. The purpose of our study was to evaluate the diagnostic accuracy of frozen section. We retrospectively reviewed 1,111 lung adenocarcinomas from January to March 2016 to evaluate the diagnostic performance of frozen section. A derivation cohort consisting of 436 cases of adenocarcinoma in situ or minimally invasive adenocarcinoma diagnosed by frozen section in the same period were analyzed to find predictive factors for invasive adenocarcinoma as the final diagnosis. Validation cohorts (first: April to June 2016, second: January to March 2015) were included to confirm the results. The overall concordance rate between frozen section and final diagnosis was 92%. Most frozen section errors were underestimation. The sensitivity of frozen section diagnosis for minimally invasive adenocarcinoma (74%) was significantly lower than others. Intraoperatively measured tumor size was the only independent factor for invasive adenocarcinoma as the final diagnosis (<1 cm: 2%, reference; 1-1.4 cm: 15%, odds ratio, 5.678; > 1.5 cm: 18%, odds ratio, 5.878; P = 0.001) in the derivation cohort, and was confirmed by validation cohorts. Fifty-nine misdiagnosed invasive adenocarcinomas in the three cohorts consisted of 54 lepidic predominant type, 1 papillary and 4 acinar predominant type. There were no positive N1, N2 node, pleural, lymphatic and vascular invasion cases found. Thirty-seven (37/59, 63%) cases of misdiagnosis were attributed to sampling error, which was the main reason. Our study suggests that adenocarcinoma in situ or minimally invasive adenocarcinoma ≥1 cm by frozen section were more likely to be invasive adenocarcinoma because of sampling error. Frozen section diagnosis of adenocarcinoma in situ or minimally invasive adenocarcinoma should be considered cautiously for tumors ≥1 cm to avoid potentially insufficient resection.

Lymph Node Micrometastasis Prognosticates Survival for Patients with Stage 1 Bronchogenic Adenocarcinoma.

BACKGROUND: This study aimed to investigate the significance of lymph node micrometastasis (LNMM) in the lung cancer nodal categories. METHODS: Between 1 January 2009 and 31 December 2013, 589 patients with suspected c-stage 1 and p-T1-2aN0-1M0 lung adenocarcinoma were enrolled in this study. The study evaluated LNMM with cytokeratin (AE1/AE3) and transcription factor-1 (TTF1) (8G7G3/1) expression by immunohistochemistry. Recurrence-free survival (RFS) and overall survival (OS) were compared among the T1-2aN0-1M0 patients stratified by the new N categories. RESULTS: From 589 patients, 7892 removed lymph nodes were examined, and LNMM was observed in 55 (9.3%) of the patients. The patients without LNMM or N1 had the best RFS (5-year rate: 80% vs 25%; P < 0.001) and OS (5-year rate: 87% vs 43%; P < 0.001), followed by the patients with LNMM, compared with those in the N1 category (RFS: 5-year rate, 25% vs 8%; P = 0.010; OS: 5-year rate, 43% vs 20%; P = 0.009). Similarly, this trend was observed when patients were subdivided into the T1 and T2a categories. Multivariate analysis showed that the new N categories with the addition of LNMM were an independent prognostic factor. This result also was noticed in all subgroups. CONCLUSIONS: The findings showed LNMM to be clinically significant as a risk factor for lung cancer. Clinicians should consider LNMM when estimating N categories to determine prognosis and the best treatment strategy.

TSLP-activated dendritic cells induce T helper type 2 inflammation in Aspergillus fumigatus keratitis.

Thymic stromal lymphopoietin (TSLP) is an IL-7-like cytokine, which is secreted by epithelial cells under the stimulation of Toll-like receptor (TLR) ligands. Dendritic cells (DCs) which express the thymic stromal lymphopoietin receptor (TSLPR) can be activated by TSLP. Mature DCs can express the OX40 ligand, which has the ability to combine with OX40 on the surface of T cells to stimulate T cell proliferation. TSLP secreted by corneal epithelial cells can engage in the process of T helper type 2 (Th2) inflammation in Aspergillus fumigatus keratitis, but the mechanism remains unclear. We demonstrated that in A. fumigatus-infected corneas, DCs aggregated, matured, and gradually migrated not only from the basement membrane to the corneal epithelium, but also from the corneal limbus to the central cornea. Mature DCs secreted Th2-attracting chemokines, the thymus and activation-regulated chemokine (TARC), and the macrophage-derived chemokine (MDC), encouraging the secretion of TNF-α and Th2 cytokine Interleukin (IL) -4, IL-5, and IL-13. The above processes were all restricted with subconjunctivally injection of TSLP siRNA, while they were strengthened with the injection of rTSLP. We demonstrated that in A. fumigatus keratitis, TSLP, through combination with TSLPR on the surface of DCs, induced DC aggregation, maturation, and migration, and then the mature DCs secreted Th2-attracting chemokines, promoting the secretion of proinflammatory cytokine TNF-α and Th2 cytokines, which finally induced Th2 inflammation.

The predictive value of CT-based radiomics in differentiating indolent from invasive lung adenocarcinoma in patients with pulmonary nodules.

OBJECTIVES: Adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) are assumed to be indolent lung adenocarcinoma with excellent prognosis. We aim to identify these lesions from invasive adenocarcinoma (IA) by a radiomics approach. METHODS: This retrospective study was approved by institutional review board with a waiver of informed consent. Pathologically confirmed lung adenocarcinomas manifested as lung nodules less than 3 cm were retrospectively identified. In-house software was used to quantitatively extract 60 CT-based radiomics features quantifying nodule's volume, intensity and texture property through manual segmentation. In order to differentiate AIS/MIA from IA, least absolute shrinkage and selection operator (LASSO) logistic regression was used for feature selection and developing radiomics signatures. The predictive performance of the signature was evaluated via receiver operating curve (ROC) and calibration curve, and validated using an independent cohort. RESULTS: 402 eligible patients were included and divided into the primary cohort (n = 207) and the validation cohort (n = 195). Using the primary cohort, we developed a radiomics signature based on five radiomics features. The signature showed good discrimination between MIA/AIS and IA in both the primary and validation cohort, with AUCs of 0.95 (95% CI, 0.91-0.98) and 0.89 (95% CI, 0.84-0.93), respectively. Multivariate logistic analysis revealed that the signature (OR, 13.3; 95% CI, 6.2-28.5; p < 0.001) and gender (OR, 3.5; 95% CI, 1.2-10.9; p = 0.03) were independent predictors of indolent lung adenocarcinoma. CONCLUSION: The signature based on radiomics features helps to differentiate indolent from invasive lung adenocarcinoma, which might be useful in guiding the intervention choice for patients with pulmonary nodules. KEY POINTS: • Based on radiomics features, a signature is established to differentiate adenocarcinoma in situ and minimally invasive adenocarcinoma from invasive lung adenocarcinoma.

Prognosis of primary tracheal tumor: A population-based analysis.

BACKGROUND: To elucidate the survival outcomes of tracheal tumors and to propose the potential stage of tracheal tumors. METHOD: All cases of primary tracheal malignant tumors were extracted from the Surveillance, Epidemiology, and End Results database (SEER) during 1973-2013. The overall survival was calculated using Kaplan-Meier method. Cox regression was utilized to identify the prognostic factors. RESULT: A total of 287 cases were finally included. The median age of the patients was 59 years. Male patients accounted for 56.1%. The median survival was 57 months. Patients were categorized as Extension1 to 4 (E1-4) and N0-N3. E1 group with size <4 cm had the best prognosis. While E1 >4 cm, E2 and E3 <3 cm groups had similar outcomes, which were superior to E3 >3 cm group. E4 was the worst. N0 patients had ideal prognosis, which were better than N1 and N2 patients. The 3-year survival rates of each T category were 74.7%, 57.3%, 28.1%, and 9.1%, respectively. In multivariate analysis, age, histology, tumor size, and extension were independent prognostic factors. CONCLUSION: Patients with old age, large tumor size, advanced extension or no surgery may have worse prognosis. The proposed T category of tracheal tumor incorporating tumor extension and size helped to predict survival outcomes.

Development and validation of a nomogram to estimate the pretest probability of cancer in Chinese patients with solid solitary pulmonary nodules: A multi-institutional study.

OBJECTIVES: To develop and validate a nomogram to estimate the pretest probability of malignancy in Chinese patients with solid solitary pulmonary nodule (SPN). MATERIALS AND METHODS: A primary cohort of 1798 patients with pathologically confirmed solid SPNs after surgery was retrospectively studied at five institutions from January 2014 to December 2015. A nomogram based on independent prediction factors of malignant solid SPN was developed. Predictive performance also was evaluated using the calibration curve and the area under the receiver operating characteristic curve (AUC). RESULTS: The mean age of the cohort was 58.9 ± 10.7 years. In univariate and multivariate analysis, age; history of cancer; the log base 10 transformations of serum carcinoembryonic antigen value; nodule diameter; the presence of spiculation, pleural indentation, and calcification remained the predictive factors of malignancy. A nomogram was developed, and the AUC value (0.85; 95%CI, 0.83-0.88) was significantly higher than other three models. The calibration cure showed optimal agreement between the malignant probability as predicted by nomogram and the actual probability. CONCLUSIONS: We developed and validated a nomogram that can estimate the pretest probability of malignant solid SPNs, which can assist clinical physicians to select and interpret the results of subsequent diagnostic tests.

Supplement CT-Guided Microcoil Placement for Localising Ground-glass Opacity (GGO) Lesions at "Blind Areas" of the Conventional Hook-Wire Technique.

BACKGROUND: In the conventional hook-wire technique of pulmonary nodular localisations there are several "blind areas", including the mediastinum-vicinity region, interlobar fissure-neighbouring areas and scapulae-shadowed areas. The present study aims to summarise the experiences of CT-guided microcoil placement as an alternative method for localising pulmonary ground-glass opacity (GGO) lesions before thoracoscopic wedge resections. METHODS: Sixteen GGO lesions at "blind areas" in 16 patients were localised with platinum-fibered microcoils under CT assistance before undergoing video-assisted thoracoscopic surgical resections. Information regarding coil placement, operations and complications was recorded. RESULTS: Of all lesions, 1 was in the mediastinum-vicinity region, 8 were covered by the scapulae, and 7 were close to interlobar fissures (3 horizontal fissures, 4 oblique fissures). All 16 (100%) lesions had been successfully marked with microcoils. No major complications of the puncture procedure occurred; there were only minor pneumothorax (n=2) and haemoptysis (n=1) complications, which required no intervention before operations. All GGO lesions and microcoils were successfully removed by initial wedge resections. Of the 16 lesions in "blind areas", 8 were adenocarcinoma in situ (AIS), 4 were minimally invasive adenocarcinoma (MIA), 3 were atypical adenomatous hyperplasia (AAH), and 1 was interstitial fibrous tissue proliferation. No major complications occurred postoperatively. CONCLUSIONS: For the "blind areas" of the hook-wire technique, CT-guided microcoil placement is an effective method of marking GGO lesions that makes thoracoscopic wedge resection easier.

Clinical and radiological features of synchronous pure ground-glass nodules observed along with operable non-small cell lung cancer.

BACKGROUND: It is common to observe synchronous pure ground-glass nodules (PGN) along with operable primary tumor on initial CT scans while clinical and radiological features of these PGNs remain unclear. METHODS: We included patients with primary tumor and PGNs detected between June 2010 and December 2013 retrospectively. The radiographic manifestations of all PGNs, pathologic findings of resected PGNs, and follow-up outcomes of unresected PGNs were analyzed to determine the predictors of malignant PGNs. RESULTS: Overall, 84 PGNs in 71 patients were included, of which 41 were resected at primary surgery and 43 were followed up. In resected group, there were 17 carcinomatous PGNs, 11 atypical adenomatous hyperplasia, and 13 benign lesions. In a follow-up group, 7 out of 43 PGNs grew, out of which four PGNs were diagnosed as adenocarcinoma and the remaining three PGNs were still followed up. In univariate analysis, size (P < 0.001), air bronchogram (P = 0.001), bubble lucency (P = 0.038), and pleural tag (P = 0.004) were the factors for malignant potential of PGNs. Multivariate analysis showed that size was an independent risk factor (P = 0.005), and the cut-off value was 9.4 mm. CONCLUSIONS: The initial size and imaging signs may be useful in assessing the malignant potential of synchronous PGNs before surgery. J. Surg. Oncol. 2016;113:738-744. © 2016 Wiley Periodicals, Inc.