Publications by authors named "Yubao Guan"

30 Publications

  • Page 1 of 1

Deep CNN Model Using CT Radiomics Feature Mapping Recognizes EGFR Gene Mutation Status of Lung Adenocarcinoma.

Front Oncol 2020 12;10:598721. Epub 2021 Feb 12.

Department of Radiology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

To recognize the epidermal growth factor receptor (EGFR) gene mutation status in lung adenocarcinoma (LADC) has become a prerequisite of deciding whether EGFR-tyrosine kinase inhibitor (EGFR-TKI) medicine can be used. Polymerase chain reaction assay or gene sequencing is for measuring EGFR status, however, the tissue samples by surgery or biopsy are required. We propose to develop deep learning models to recognize EGFR status by using radiomics features extracted from non-invasive CT images. Preoperative CT images, EGFR mutation status and clinical data have been collected in a cohort of 709 patients (the primary cohort) and an independent cohort of 205 patients. After 1,037 CT-based radiomics features are extracted from each lesion region, 784 discriminative features are selected for analysis and construct a feature mapping. One Squeeze-and-Excitation (SE) Convolutional Neural Network (SE-CNN) has been designed and trained to recognize EGFR status from the radiomics feature mapping. SE-CNN model is trained and validated by using 638 patients from the primary cohort, tested by using the rest 71 patients (the internal test cohort), and further tested by using the independent 205 patients (the external test cohort). Furthermore, SE-CNN model is compared with machine learning (ML) models using radiomics features, clinical features, and both features. EGFR(-) patients show the smaller age, higher odds of female, larger lesion volumes, and lower odds of subtype of acinar predominant adenocarcinoma (APA), compared with EGFR(+). The most discriminative features are for texture (614, 78.3%) and the features of first order of intensity (158, 20.1%) and the shape features (12, 1.5%) follow. SE-CNN model can recognize EGFR mutation status with an AUC of 0.910 and 0.841 for the internal and external test cohorts, respectively. It outperforms the CNN model without SE, the fine-tuned VGG16 and VGG19, three ML models, and the state-of-art models. Utilizing radiomics feature mapping extracted from non-invasive CT images, SE-CNN can precisely recognize EGFR mutation status of LADC patients. The proposed method combining radiomics features and deep leaning is superior to ML methods and can be expanded to other medical applications. The proposed SE-CNN model may help make decision on usage of EGFR-TKI medicine.
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http://dx.doi.org/10.3389/fonc.2020.598721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907520PMC
February 2021

An antibiotic stewardship programme to reduce inappropriate antibiotic prescribing for acute respiratory infections in rural Chinese primary care facilities: study protocol for a clustered randomised controlled trial.

Trials 2020 May 12;21(1):394. Epub 2020 May 12.

National Center for Respiratory Diseases, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, Laboratory of Guangdong-Hong Kong -Macao Great Bay, Guangzhou Medical University, 151 Yanjiang Xi Rd, Guangzhou City, 510120, Guangdong, China.

Background: Inappropriate prescribing of antibiotics for acute respiratory infections at the primary care level represents the major source of antibiotic misuse in healthcare, and is a major driver for antimicrobial resistance worldwide. In this study we will develop, pilot and evaluate the effectiveness of a comprehensive antibiotic stewardship programme in China's primary care hospitals to reduce inappropriate prescribing of antibiotics for acute respiratory infections among all ages.

Methods: We will use a parallel-group, cluster-randomised, controlled, superiority trial with blinded outcome evaluation but unblinded treatment (providers and patients). We will randomise 34 primary care hospitals from two counties within Guangdong province into the intervention and control arm (1:1 overall ratio) stratified by county (8:9 within-county ratio). In the control arm, antibiotic prescribing and management will continue through usual care. In the intervention arm, we will implement an antibiotic stewardship programme targeting family physicians and patients/caregivers. The family physician components include: (1) training using new operational guidelines, (2) improved management and peer-review of antibiotic prescribing, (3) improved electronic medical records and smart phone app facilitation. The patient/caregiver component involves patient education via family physicians, leaflets and videos. The primary outcome is the proportion of prescriptions for acute respiratory infections (excluding pneumonia) that contain any antibiotic(s). Secondary outcomes will address how frequently specific classes of antibiotics are prescribed, how frequently key non-antibiotic alternatives are prescribed and the costs of consultations. We will conduct a qualitative process evaluation to explore operational questions regarding acceptability, cultural appropriateness and burden of technology use, as well as a cost-effectiveness analysis and a long-term benefit evaluation. The duration of the intervention will be 12 months, with another 24 months' post-trial long-term follow-up.

Discussion: Our study is one of the first trials to evaluate the effect of an antibiotic stewardship programme in primary care settings in a low- or middle-income country (LMIC). All interventional activities will be designed to be embedded into routine primary care with strong local ownership. Through the trial we intend to impact on clinical practice and national policy in antibiotic prescription for primary care facilities in rural China and other LMICs.

Trial Registration: ISRCTN, ID: ISRCTN96892547. Registered on 18 August 2019.
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http://dx.doi.org/10.1186/s13063-020-04303-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7216131PMC
May 2020

Etiological distribution and clinical features of fever of unknown origin with pulmonary lesions in South China.

Clin Respir J 2019 Nov 1;13(11):683-692. Epub 2019 Sep 1.

The State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.

Introduction: Fever of unknown origin (FUO) with pulmonary lesions is a common syndrome in respiratory diseases, which can be caused by infection, cancer, connective tissue disease and other rare diseases of South China. In patients with FUO associated with pulmonary lesions, pathogeny should be identified and followed by an appropriate treatment strategy.

Objective: This study aimed to investigate the etiological distribution and clinical features of FUO with pulmonary lesions and to analyze the efficiency of different diagnostic methods for certain disease categories.

Methods: Patients hospitalized at the Guangzhou Institute of Respiratory Health from July 2012 to December 2016 who had fever ≥38.3°C that lasted ≥21 days, in whom the chest X-ray or computed tomography (CT) revealed definite pulmonary infiltration, and for whom, despite being examined for a week, no definitive diagnosis could be made, were considered for this study.

Results: A total of 104 patients were identified as having FUO with lung lesions, and 89.4% (93/104) patients were definitively diagnosed. Infectious disease was the most common cause (46.2%, 48/104). Histopathology was instrumental in the diagnosis of the causes of FUO with pulmonary manifestations, 47.3% (44/93) patients were diagnosed through histopathology, 35.4% (17/48) with infectious disease and 55.2% (16/29) with connective tissue diseases as the etiology were definitely diagnosed using histopathology.

Conclusion: Most FUO with pulmonary lesions are identified during infections and autoimmune diseases. The most important diagnostic measure for FUO with pulmonary lesions is histopathology. Additionally, lung biopsy must be encouraged in multi-level hospitals in the future.
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http://dx.doi.org/10.1111/crj.13070DOI Listing
November 2019

Computed Tomography-Based Radiomics Signature: A Potential Indicator of Epidermal Growth Factor Receptor Mutation in Pulmonary Adenocarcinoma Appearing as a Subsolid Nodule.

Oncologist 2019 11 1;24(11):e1156-e1164. Epub 2019 Apr 1.

Department of Radiology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China

Background: Lung adenocarcinoma (LADC) with epidermal growth factor receptor (EGFR) mutation is considered a subgroup of lung cancer sensitive to EGFR-targeted tyrosine kinase inhibitors. We aimed to develop and validate a computed tomography (CT)-based radiomics signature for prediction of EGFR mutation status in LADC appearing as a subsolid nodule.

Materials And Methods: A total of 467 eligible patients were divided into training and validation cohorts ( = 306 and 161, respectively). Radiomics features were extracted from unenhanced CT images by using Pyradiomics. A CT-based radiomics signature for distinguishing EGFR mutation status was constructed using the random forest (RF) method in the training cohort and then tested in the validation cohort. A combination of the radiomics signature with a clinical factors model was also constructed using the RF method. The performance of the model was evaluated using the area under the curve (AUC) of a receiver operating characteristic curve.

Results: In this study, 64.2% (300/467) of the patients showed EGFR mutations. L858R mutation of exon 21 was the most common mutation type (185/301). We identified a CT-based radiomics signature that successfully discriminated between EGFR positive and EGFR negative in the training cohort (AUC = 0.831) and the validation cohort (AUC = 0.789). The radiomics signature combined with the clinical factors model was not superior to the simple radiomics signature in the two cohorts ( > .05).

Conclusion: As a noninvasive method, the CT-based radiomics signature can be used to predict the EGFR mutation status of LADC appearing as a subsolid nodule.

Implications For Practice: Lung adenocarcinoma (LADC) with epidermal growth factor receptor (EGFR) mutation is considered a subgroup of lung cancer that is sensitive to EGFR-targeted tyrosine kinase inhibitors. However, some patients with inoperable subsolid LADC are unable to undergo tissue sampling by biopsy for molecular analysis in clinical practice. A computed tomography-based radiomics signature may serve as a noninvasive biomarker to predict the EGFR mutation status of subsolid LADCs when mutational profiling is not available or possible.
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http://dx.doi.org/10.1634/theoncologist.2018-0706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6853103PMC
November 2019

Uncontrolled asthma phenotypes defined from parameters using quantitative CT analysis.

Eur Radiol 2019 Jun 7;29(6):2848-2858. Epub 2019 Jan 7.

National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China.

Objective: Asthma is a heterogeneous disease with diverse clinical phenotypes that have been identified via cluster analyses. However, the classification of phenotypes based on quantitative CT (qCT) is poorly understood. The study was conducted to investigate CT determination of uncontrolled asthma phenotypes.

Methods: Sixty-five patients with uncontrolled asthma (37 with severe asthma, 28 with non-severe asthma) underwent detailed clinical, laboratory, and pulmonary function tests, as well as qCT analysis. Twenty-five healthy subjects were also included in this study and underwent clinical physical examinations, pulmonary function tests, and low-dose CT scans.

Results: The mean lumen area/body surface area ratio was smaller in patients with severe uncontrolled asthma compared with that in healthy subjects (9.84 mm [SD, 2.57 mm], 11.96 mm [SD, 3.09 mm]; p = 0.026). However, the percentage of mean wall area (WA) was greater (64.39% [SD, 2.55%], 62.09% [SD, 3.81%], p = 0.011). Air trapping (measured based on mean lung density and VI [%] on expiratory scan) was greater in patients with severe uncontrolled asthma than in those with non-severe uncontrolled asthma and was higher in all patients with uncontrolled asthma than that in healthy subjects (all p < 0.001). Three CT-determined uncontrolled asthma phenotypes were identified. Cluster 1 had mild air trapping with or without proximal airway remodeling. Cluster 2 had moderate air trapping with or without proximal airway remodeling. Cluster 3 had severe air trapping with proximal airway remodeling.

Conclusions: There was obvious air trapping and proximal airway remodeling in patients with severe uncontrolled asthma. The three CT-determined uncontrolled asthma phenotypes might reflect underlying mechanisms of disease in patient stratification and in the different stages of disease development.

Key Points: • Obvious air trapping and proximal airway remodeling were present in patients with severe uncontrolled asthma. • CT air trapping indices showed a good correlation with disease duration, total IgE, atopy, and OCS and ICS doses, and were even more strongly correlated with clinical lung function. • Three CT-determined uncontrolled asthma phenotypes were identified, which might reflect underlying mechanisms of disease in patient stratification and in the different stages of disease development.
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http://dx.doi.org/10.1007/s00330-018-5913-1DOI Listing
June 2019

CT-based radiomics signature for differentiating solitary granulomatous nodules from solid lung adenocarcinoma.

Lung Cancer 2018 11 17;125:109-114. Epub 2018 Sep 17.

Department of Radiology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Diseases, Guangzhou, China. Electronic address:

Objectives: Pulmonary granulomatous nodule (GN) with spiculated or lobulated appearance are indistinguishable from solid lung adenocarcinoma (SADC) based on CT morphological features, and partial false-positive findings on PET/CT. The objective of this study was to investigate the ability of quantitative CT radiomics for preoperatively differentiating solitary atypical GN from SADC.

Methods: 302 eligible patients (SADC = 209, GN = 93) were evaluated in this retrospective study and were divided into training (n = 211) and validation cohorts (n = 91). Radiomics features were extracted from plain and vein-phase CT images. The L1 regularized logistic regression model was used to identify the optimal radiomics features for construction of a radiomics model in differentiate solitary GN from SADC. The performance of the constructed radiomics model was evaluated using the area under curve (AUC) of receiver operating characteristic curve (ROC).

Results: 16.7% (35/209) of SADC were misdiagnosed as GN and 24.7% (23/93) of GN were misdiagnosed as lung cancer before surgery. The AUCs of combined radiomics and clinical risk factors were 0.935, 0.902, and 0.923 in the training cohort of plain radiomics(PR), vein radiomics, and plain and vein radiomics, and were 0.817, 0835, and 0.841 in the validation cohort of three models, respectively. PR combined with clinical risk factors (PRC) performed better than simple radiomics models (p < 0.05). The diagnostic accuracy of PRC in the total cohorts was similar to our radiologists (p ≥ 0.05).

Conclusions: As a noninvasive method, PRC has the ability to identify SADC and GN with spiculation or lobulation.
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http://dx.doi.org/10.1016/j.lungcan.2018.09.013DOI Listing
November 2018

Correlations between computed tomography and positron emission tomography/computed tomography findings and pathology in 6 cases of pulmonary epithelioid angiosarcoma.

Medicine (Baltimore) 2018 Aug;97(35):e12107

Department of Radiology Department of Pathology, the First Affiliated Hospital of Guangzhou Medical University Guangzhou Institute of Respiratory Health, Guangzhou, China.

Previous studies on primary pulmonary epithelioid angiosarcoma (PEA) have been mostly clinical or pathological case reports. We here summarize findings from computed tomography (CT) and positron emission tomography/computed tomography (PET/CT) analyses of PEA to improve the diagnosis and differentiation of this rare tumor.We conducted a retrospective analysis of the clinical findings, radiological imaging, and pathological findings of 6 cases of primary PEA confirmed by surgery, biopsy, and pathology. All cases were evaluated by CT and x-ray prior to surgery, and 2 cases were further examined by PET/CT.CT images indicated maximum tumor diameters of 2.4 to 9.8 cm and inhomogeneous density, with 1 case exhibiting nodular calcification. Contrast-enhanced CT revealed inhomogeneous enhancement with visible necrosis in all 6 cases, while 3 cases had hilar and mediastinal lymph node metastasis. Five cases displayed extensive tumor involvement with extension into the chest wall, mild-to-moderate levels of pleural effusion, and varying degrees of volume loss in the corresponding hemithorax. One case had limited pleural thickening and invasion. Preoperative PET/CT of 1 case revealed abnormal fluorine-18 fluorodeoxyglucose (F-FDG) uptake by the tumor and multiple enlarged right hilar and mediastinal lymph nodes, right diffuse pleural thickening, and systemic multiple bone metastasis. In the other case, PET/CT scan at 7 months after surgery revealed pleural thickening and mediastinal lymph nodes with increased F-FDG uptake on the surgical side. Immunohistochemistry analyses determined that all 6 tumors were positive for CD34, CD31, ERG, and vimentin.CT and PET/CT findings reveal that malignant characteristics, including extensive pleural thickening, invasion and metastasis, and pleural effusion, are common in PEA. Imaging data are only supportive; therefore, the final diagnosis should be based on pathology and immunohistochemistry analyses.
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http://dx.doi.org/10.1097/MD.0000000000012107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6392945PMC
August 2018

A new approach to predict lymph node metastasis in solid lung adenocarcinoma: a radiomics nomogram.

J Thorac Dis 2018 Apr;10(Suppl 7):S807-S819

Department of Radiology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.

Background: Lymph node metastasis (LNM) of lung cancer is an important factor related to survival and recurrence. The association between radiomics features of lung cancer and LNM remains unclear. We developed and validated a radiomics nomogram to predict LNM in solid lung adenocarcinoma.

Methods: A total of 159 eligible patients with solid lung adenocarcinoma were divided into training (n=106) and validation cohorts (n=53). Radiomics features were extracted from venous-phase CT images. We built a radiomics nomogram using a multivariate logistic regression model combined with CT-reported lymph node (LN) status. The performance of the radiomics nomogram was evaluated using the area under curve (AUC) of receiver operating characteristic curve. We performed decision curve analysis (DCA) within training and validation cohorts to assess the clinical usefulness of the nomogram.

Results: Fourteen radiomics features were chosen from 94 candidate features to build a radiomics signature that significantly correlated with LNM. The model showed good calibration and discrimination in the training cohort, with an AUC of 0.871 (95% CI: 0.804-0.937), sensitivity of 85.71% and specificity of 77.19%. In the validation cohort, AUC was 0.856 (95% CI: 0.745-0.966), sensitivity was 91.66%, and specificity was 82.14%. DCA demonstrated that the nomogram was clinically useful. The nomogram also showed good predictive ability in patients at high risk for LNM in the CT-reported LN negative (cN0) subgroup.

Conclusions: The radiomics nomogram, based on preoperative CT images, can be used as a noninvasive method to predict LNM in patients with solid lung adenocarcinoma.
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http://dx.doi.org/10.21037/jtd.2018.03.126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5945690PMC
April 2018

Malignant solitary pulmonary nodules: assessment of mass growth rate and doubling time at follow-up CT.

J Thorac Dis 2018 Apr;10(Suppl 7):S797-S806

The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China.

Background: The differentiation of benign and malignant solitary pulmonary nodules (SPNs), especially subsolid nodules, is still challenging because of the small size, slow growth, and atypical imaging characteristics of these nodules. We aimed to determine the significance of mass growth rate (MGR) and mass doubling time (MDT) at follow-up CT of malignant SPNs.

Methods: This retrospective study included 167 patients (169 SPNs, diameter 8-30 mm). Among the 169 SPNs, 114 malignant SPNs were classified into three types: pure ground-glass nodules (pGGNs), part-solid nodules (pSNs), and solid nodules (SNs). These patients were followed up for at least 3 months. Three-dimensional manual segmentation was performed for all these nodules, and the intra- and inter-observer variabilities of diameter, volume, and mass measurement were assessed. From initial and follow-up CT scans, growth rates of the diameter, volume, and mass of the SPNs were compared. MDT and volume doubling time (VDT) were calculated and were compared among groups.

Results: Mass measurements had the best inter-observer consistency and intra-observer repeatability; the coefficients of variation of the mass measurements were the smallest. The mean growth rates of the diameter, volume, and mass of pGGNs, pSNs, and SNs significantly differed at different time points (P<0.001). Mean MDTs and VDTs of pGGNs, pSNs, and SNs were 655 848 days, 462 598 days, and 230 267 days, respectively (P<0.05).

Conclusions: Mass measurements are an objective and accurate indicator in SPN assessment. During a 2-year follow-up, the mean growth rates of the diameter, volume, and mass of pGGNs, pSNs, and SNs differed at different time points, the greatest difference was observed in mean MGR. Mean MDT of malignant SPNs is less than the mean VDT.
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http://dx.doi.org/10.21037/jtd.2018.04.25DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5945695PMC
April 2018

Is a 5-mm diameter an appropriate cut-off value for the diagnosis of atypical adenomatous hyperplasia and adenocarcinoma in situ on chest computed tomography and pathological examination?

J Thorac Dis 2018 Apr;10(Suppl 7):S790-S796

Department of Radiology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.

Background: Preinvasive lesions, such as atypical adenomatous hyperplasia (AAH) and adenocarcinoma in situ (AIS), usually appear as pure ground-glass nodules (pGGNs) on thin-section computed tomography (TSCT). AAH is usually less than 5 mm wide on imaging and pathological examinations. We aimed to determine whether a 5-mm cut-off value was appropriate for the diagnosis of AAH and AIS.

Methods: We retrospectively analyzed the performance of TSCT in evaluating 80 pathologically confirmed preinvasive lesions (33 AAH lesions in 31 patients and 47 AIS lesions in 45 patients). We compared the following characteristics between the AAH and AIS groups: lesion diameter, density, rim, lobulation, spiculation, vacuole sign, aerated bronchus sign, pleural indentation sign, and pathological findings.

Results: All 80 lesions appeared as pGGNs. On TSCT, the average diameter of AAH lesions (6.0±1.64 mm) was significantly smaller than that of AIS lesions (8.7±3.16 mm; P<0.001). The area under the curve (AUC) for diameter was 0.792, and the best diagnostic cut-off value was 6.99 mm. On gross pathological examination, the average diameter of AAH lesions (4.6±1.99 mm) was significantly smaller that of AIS lesions (6.8±2.06 mm; P<0.001). The AUC was 0.794, and the best diagnostic cut-off value was 4.5 mm. The vacuole sign was common in AIS (P=0.021). AAH did not significantly differ from AIS (P>0.05) in terms of average CT value, uniformity of density, morphology, rim, lobulation, spiculation, pleural indentation sign, and aerated bronchus sign.

Conclusions: Lesion size and the vacuole sign were beneficial in the diagnosis of AAH and AIS. The vacuole sign was common in AIS. The best diagnostic cut-off value of nodular diameter for differentiating between AAH and AIS was 6.99 mm on TSCT and 4.5 mm on gross pathology.
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http://dx.doi.org/10.21037/jtd.2017.12.124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5945684PMC
April 2018

Stage I synchronous multiple primary non-small cell lung cancer: CT findings and the effect of TNM staging with the 7th and 8th editions on prognosis.

J Thorac Dis 2017 Dec;9(12):5335-5344

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.

Background: Studies have reported that up to 8% of non-small cell lung cancers (NSCLC) involve multiple lesions; no detailed study has assessed the prognosis of early synchronous multiple primary non-small cell lung cancer (SMPNSCLC) (T1N0M0, T2aN0M0). We aimed to assess the spiral CT manifestations of SMPNSCLC during stage I and evaluate the effect of TNM staging with the 7th and 8th editions on the prognosis.

Methods: We retrospectively analyzed the data of patients who were examined, operated, and pathologically confirmed as having NSCLC from January 1, 2009, to December 31, 2010, and were followed-up for 5 years. The number of cases with stage I SMPNSCLC and solitary primary NSCLC (SPNSCLC) was 36 and 133 as per the 7th edition TNM staging system and 34 and 111 as per the 8th edition TNM staging system, respectively. The relationship between sex, age, smoking history, emphysema, surgical procedure, pathological type, tumor location, and tumor size was evaluated between the two groups, along with the correlation between prognosis and TNM staging with the 7th and 8th editions.

Results: A total of 1,948 cases of NSCLC underwent surgery, including 36 cases of stage I SMPNSCLC (77 lesions; 1.85%) with an age of onset of 44-86 years (median age, 60 years). The tumors primarily included adenocarcinoma (93.5%), with a diameter of 0.4-4.5 cm (median, 2.3 cm). CT indicated round/oval tumors in 81.8% cases, lobulation in 79.2% cases, spiculation sign in 70.1% cases, bronchial truncation sign in 31.2% cases, and pleural indentation in 75.3% cases. Moreover, CT indicated the presence of 36 (46.8%) solid nodules and 41 (53.2%) sub-solid nodules. With the 7th edition TNM staging system, the 5-year overall survival (OS) and disease-free survival (DFS) rates for stage ISMPNSCLC were 86.1% and 72.2%, respectively, which did not significantly differ from the prognosis of 133 cases of stage I SPNSCLC (P=0.587, P=0.273). With the 8th edition TNM staging system, the 5-year OS and DFS rates for stage I SMPNSCLC were 88.2% and 73.5%, respectively, which also did not significantly differ with the prognosis of 111 cases of stage I SPNSCLC (P=0.413, P=0.235).

Conclusions: Adenocarcinoma was the main pathological type among the cases with stage I SMPNSCLC. Multiple synchronous lesions almost had the malignant characteristics of primary lung cancer, particularly the presence of single or multiple sub-solid nodules. Moreover, stage I SMPNSCLC has a similar prognosis as stage I SPNSCLC. The postoperative outcomes of stage I SMPNSCLC patients remained consistent regardless of whether the 7th or 8th edition TNM staging system was used for staging.
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http://dx.doi.org/10.21037/jtd.2017.12.101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5757034PMC
December 2017

Erlotinib intercalating pemetrexed/cisplatin versus erlotinib alone in Chinese patients with brain metastases from lung adenocarcinoma: a prospective, non-randomised, concurrent controlled trial (NCT01578668).

ESMO Open 2017 7;2(Suppl 1):e000112. Epub 2017 Mar 7.

Department of Pharmacy, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Objective: Erlotinib has a synergistic effect with pemetrexed for treating non-squamous non-small-cell lung cancer. We investigated the efficacy and safety of erlotinib (E) in combination with pemetrexed/cisplatin (E-P) in Chinese patients with lung adenocarcinoma with brain metastases.

Design: Patients who were erlotinib-naïve or pemetrexed-naïve were assigned in parallel to receive either E or E-P. The primary endpoint was the intracranial overall response rate (ORRi).

Results: Sixty-nine patients with lung adenocarcinoma with brain metastases received E (n=35) or E-P (n=34) from January 2012 to November 2014. Demographics and patient characteristics were well balanced between the two groups, including epidermal growth factor receptor () status, sex, age, smoking status, Eastern Cooperative Oncology Group (ECOG) performance status, brain metastases and number of prior treatments. ORRi in the E-P arm was superior to that in the E arm (79% vs 48%, p=0.008). Compared with E as the first-line treatment, E-P was associated with better intracranial progression-free survival (PFSi, median: 9 vs 2 months, p=0.027) and systemic PFS (median: 8 vs 2 months, p=0.006). The most frequent E-related adverse events were higher in the combination arm. No new safety signals were detected. The side effects were tolerable, and there were no drug-related deaths.

Conclusion: Our study suggests that the E-P combination may be effective in Chinese patients with lung adenocarcinoma with brain metastases, with improved PFS in treatment-naïve patients. Toxicities are tolerable, and there are more E-related side effects.
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http://dx.doi.org/10.1136/esmoopen-2016-000112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5682358PMC
March 2017

Quantitative Low-Dose Computed Tomography of the Lung Parenchyma and Airways for the Differentiation between Chronic Obstructive Pulmonary Disease and Asthma Patients.

Respiration 2017 25;94(4):366-374. Epub 2017 Jul 25.

Department of Radiology, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Background: It is difficult to differentiate between chronic obstructive pulmonary disease (COPD) and asthma in clinics; therefore, for diagnostic purposes, imaging-based measurements could be beneficial to differentiate between the two diseases.

Objectives: We aim to analyze quantitative measurements of the lung and bronchial parameters that are provided by low-dose computed tomography (CT) to differentiate COPD and asthma from an imaging perspective.

Materials And Methods: 69 COPD patients, 52 asthma patients, and 20 healthy subjects were recruited to participate in CT imaging and pulmonary function tests (PFTs). Comparative analysis was performed to identify differences between COPD and asthma in CT measurements. PFT measurements enabled validation of the differentiation between COPD and asthma patients.

Results: There were significant differences among the COPD, asthma, and healthy control groups. The differences were more significant among the following: inspiratory emphysema index (EI)-950 (%), expiratory lung volume, expiratory mean lung density (MLD), and expiratory EI-950 (%) and EI-850 (%). The COPD group had a significantly higher EI-950 (%) than the asthma group (p = 0.008). There were significant differences among the three groups in lumen area (LA), wall area (WA), total area, and Pi10WA. The asthma group had significantly higher WA%/WV% than both the COPD (p = 0.002) and the control group (p = 0.012). There was high sensitivity in EI-950 (%), EI-850 (%) and expiratory MLD in the parenchyma and high sensitivity in LA and Pi10WA in small airways in the differential diagnosis of COPD and asthma.

Conclusion: To aid the diagnosis, CT can provide quantitative measurements to differentiate between COPD and asthma patients.
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http://dx.doi.org/10.1159/000478531DOI Listing
May 2018

Coexistence of p16/CDKN2A homozygous deletions and activating EGFR mutations in lung adenocarcinoma patients signifies a poor response to EGFR-TKIs.

Lung Cancer 2016 12 31;102:101-107. Epub 2016 Oct 31.

Department of Radiology, The First Affiliated Hospital, Guangzhou Medical University; Guangzhou, Guangdong, 510120, China. Electronic address:

Objectives: Activating mutations in the epidermal growth factor receptor (EGFR) are strongly predictive of EGFR-tyrosine kinase inhibitor (TKI) activity in non-small cell lung cancer (NSCLC). However, primary resistance to EGFR-TKIs occurs in approximately 20-30% of NSCLC patients with EGFR mutations. The goal of this study was to determine whether p16/CDKN2A homozygous deletion (HD) is associated with primary resistance to EGFR-TKIs in lung adenocarcinoma patients with EGFR activating mutations.

Methods: We investigated 127 patients with stage IIIB or IV lung adenocarcinoma harboring activating EGFR mutations, and who had received EGFR-TKIs as first-line therapy. Dual-color fluorescence in situ hybridization for p16/CDKN2A and chromosome 9 was performed in tumor biopsy samples obtained before initiation of EGFR-TKI treatment.

Results: p16/CDKN2A HD was detected in 24.4% (31/127) of patients, and the overall response rate in patients with and without this mutation was 48.4% and 78.1%, respectively (P=0.0027). The median progression-free survival was 5.3 months (95% confidence interval [CI]: 4.582-6.018) for patients with p16/CDKN2A HD and 10.5 months (95% CI: 9.365-11.635 months) for patients without the mutation (P=0.001). No correlations between p16/CDKN2A HD and patient characteristics including gender, age, smoking history, EGFR mutation type, tumor-node-metastasis stage, and performance status were found.

Conclusions: Our study demonstrates that the coexistence of p16/CDKN2A HDs and activating EGFR mutations in lung adenocarcinoma patients signifies a poor response to EGFR-TKI therapy.
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http://dx.doi.org/10.1016/j.lungcan.2016.10.015DOI Listing
December 2016

Preoperative evaluation of stage T3, central-type non-small cell lung cancer with double sleeve lobectomy under complete video-assisted thoracoscopic surgery using spiral computed tomography post-processing techniques.

J Thorac Dis 2016 Jul;8(7):1738-46

State Key Laboratory of Respiratory Disease, Guangzhou 510120, China;; Department of Thoracic Surgery, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.

Background: To investigate the estimated value of spiral computed tomography (CT) post-processing techniques in preoperative stage T3, central-type non-small cell lung cancer (NSCLC) with double sleeve lobectomy under complete video-assisted thoracoscopic surgery (c-VATS).

Methods: Preoperative clinical date and CT reconstructed data of 10 patients who underwent double sleeve lobectomy with upper lobe stage T3, central-type NSCLC were retrospectively analysed and compared to surgical pathological results and cross-sectional CT data. The diagnostic criterions of tumour invasion of pulmonary artery and bronchus were divided into five grades, which included estimation of upper lobe pulmonary arteries and bronchi (40 branches, respectively).

Results: The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of cross-sectional CT images of pulmonary artery tumour invasion were 78.57%, 58.33%, 81.48%, 53.85%, and 72.50%, respectively, while the respective values for CT reconstructed images were 93.55%, 87.50%, 96.67%, 70.00%, and 90.00%, showing statistical significance (χ(2)=4.021, P=0.045). Similarly, the evaluate, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of cross-sectional CT images of bronchial tumour invasion were 82.76%, 45.45%, 80.00%, 50.00%, and 72.50%, respectively, while the respective values for CT reconstructed images were 97.06%, 66.67%, 94.29%, 80.00%, 92.50%; these results were also statistically significant (χ(2)=5.541, P=0.019).

Conclusions: The sensitivity, specificity, and diagnostic accuracy of the spiral CT post-processing techniques were better than cross-sectional CT images in estimating the extent of tumour invasion in the pulmonary arteries and bronchi of central-type NSCLC. CT post-processing techniques are essential tools in preoperative examination and operative method selection of central-type lung cancer with double sleeve lobectomy under c-VATS.
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http://dx.doi.org/10.21037/jtd.2016.05.93DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4958815PMC
July 2016

Computed Tomography Manifestations and Excision Cross-Complementation Group 1 Expression of Stage I Non-Small-Cell Lung Cancer and Their Correlation With Prognosis.

J Comput Assist Tomogr 2016 Jul-Aug;40(4):584-8

From the *Department of Radiology, The First Affiliated Hospital of GuangZhou Medical University; †State Key Laboratory of Respiratory Disease; and ‡Department of Thoracic Surgery, The First Affiliated Hospital of GuangZhou Medical University, Guangzhou, China.

Objective: The aim of this study was to evaluate the computed tomography (CT) manifestations and expression of the excision cross-complementation group 1 (ERCC1) and their correlation with prognosis in stage I non-small-cell lung cancer (NSCLC).

Materials And Methods: A total of 133 patients with stage I NSCLC with complete 3- and 5-year disease-free survival (DFS) and overall survival (OS) data, who underwent thoracic CT and pathological examination, were included. Expression of ERCC1 in tumor samples was evaluated using semiquantitative immunohistochemical analysis.

Results: The 3- and 5-year DFS rates for the 133 patients were 72.2% and 60.9%, respectively, and the 3- and 5-year OS rates were 89.5% and 82.0%, respectively. Significant differences in the 3- and 5-year DFS occurred (P = 0.003 and P = 0.001, respectively), whereas no significant differences in the 3- and 5-year OS were found (P = 0.099 and P = 0.062, respectively) between high and low ERCC1 protein expression. Patients with high expression of ERCC1 had a better prognosis. There was a significant correlation between tumors with an irregular edge and signs of spiculation on CT and low expression of ERCC1 evaluated using logistic regression analysis (P < 0.05).

Conclusions: It was concluded that patients with stage I NSCLC with high ERCC1 expression had superior survival rates relative to those with low ERCC1 expression. Tumors with an irregular edge and signs of spiculation on CT were significantly correlated with low expression of ERCC1.
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http://dx.doi.org/10.1097/RCT.0000000000000416DOI Listing
January 2017

Improving lung cancer prognosis assessment by incorporating synthetic minority oversampling technique and score fusion method.

Med Phys 2016 Jun;43(6):2694-2703

School of Electrical and Computer Engineering, University of Oklahoma, Norman, Oklahoma 73019.

Purpose: This study aims to investigate the potential to improve lung cancer recurrence risk prediction performance for stage I NSCLS patients by integrating oversampling, feature selection, and score fusion techniques and develop an optimal prediction model.

Methods: A dataset involving 94 early stage lung cancer patients was retrospectively assembled, which includes CT images, nine clinical and biological (CB) markers, and outcome of 3-yr disease-free survival (DFS) after surgery. Among the 94 patients, 74 remained DFS and 20 had cancer recurrence. Applying a computer-aided detection scheme, tumors were segmented from the CT images and 35 quantitative image (QI) features were initially computed. Two normalized Gaussian radial basis function network (RBFN) based classifiers were built based on QI features and CB markers separately. To improve prediction performance, the authors applied a synthetic minority oversampling technique (SMOTE) and a BestFirst based feature selection method to optimize the classifiers and also tested fusion methods to combine QI and CB based prediction results.

Results: Using a leave-one-case-out cross-validation (K-fold cross-validation) method, the computed areas under a receiver operating characteristic curve (AUCs) were 0.716 ± 0.071 and 0.642 ± 0.061, when using the QI and CB based classifiers, respectively. By fusion of the scores generated by the two classifiers, AUC significantly increased to 0.859 ± 0.052 (p < 0.05) with an overall prediction accuracy of 89.4%.

Conclusions: This study demonstrated the feasibility of improving prediction performance by integrating SMOTE, feature selection, and score fusion techniques. Combining QI features and CB markers and performing SMOTE prior to feature selection in classifier training enabled RBFN based classifier to yield improved prediction accuracy.
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http://dx.doi.org/10.1118/1.4948499DOI Listing
June 2016

Diagnosis of lung adenocarcinoma in situ and minimally invasive adenocarcinoma from intraoperative frozen sections: an analysis of 136 cases.

J Clin Pathol 2016 Dec 12;69(12):1076-1080. Epub 2016 May 12.

Department of Cardiothoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Aims: To determine the diagnostic accuracy and contraindications for intraoperative diagnosis of lung adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) from frozen sections.

Methods: A retrospective analysis of data from 136 patients pathologically diagnosed with early-stage (T1N0M0) AIS or MIA from paraffin-embedded sections. The rate of concordance between the diagnoses from intraoperative frozen sections and paraffin-embedded sections was determined, and the interpretive features that contributed to errors and deferrals in frozen-section diagnoses were identified.

Results: Of the 136 patients, diagnoses from frozen sections and paraffin-embedded sections were concordant in 86 (63.24%) cases intraoperatively diagnosed with AIS or MIA, and 44 (32.35%) cases were intraoperatively diagnosed with adenocarcinoma as the range of infiltration could not be determined from the frozen sections. From the remaining six (4.41%) cases, the frozen section and paraffin-embedded section diagnoses were discordant. The reasons for frozen section errors and deferrals included larger tumour volume, tumour located close to the visceral pleura, interstitial inflammation or fibrosis, absence of prominent atypia and differential morphology in the deeper levels of the paraffin block.

Conclusions: Diagnosis of AIS and MIA from intraoperative frozen sections is feasible. We provide several modifications that may improve the diagnostic accuracy of intraoperative frozen sections for early-stage lung adenocarcinoma.
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http://dx.doi.org/10.1136/jclinpath-2016-203619DOI Listing
December 2016

Fusion of Quantitative Image and Genomic Biomarkers to Improve Prognosis Assessment of Early Stage Lung Cancer Patients.

IEEE Trans Biomed Eng 2016 05 14;63(5):1034-1043. Epub 2015 Sep 14.

Objective: This study aims to develop a new quantitative image feature analysis scheme and investigate its role along with two genomic biomarkers, namely protein expression of the excision repair cross-complementing 1 genes and a regulatory subunit of ribonucleotide reductase (RRM1), in predicting cancer recurrence risk of stage I nonsmall-cell lung cancer (NSCLC) patients after surgery.

Methods: By using chest computed tomography images, we developed a computer-aided detection scheme to segment lung tumors and computed tumor-related image features. After feature selection, we trained a Naïve Bayesian network-based classifier using eight image features and a multilayer perceptron classifier using two genomic biomarkers to predict cancer recurrence risk, respectively. Two classifiers were trained and tested using a dataset with 79 stage I NSCLC cases, a synthetic minority oversampling technique and a leave-one-case-out validation method. A fusion method was also applied to combine prediction scores of two classifiers.

Results: Areas under ROC curves (AUC) values are 0.78 ± 0.06 and 0.68 ± 0.07 when using the image feature and genomic biomarker-based classifiers, respectively. AUC value significantly increased to 0.84 ± 0.05 ( ) when fusion of two classifier-generated prediction scores using an equal weighting factor.

Conclusion: A quantitative image feature-based classifier yielded significantly higher discriminatory power than a genomic biomarker-based classifier in predicting cancer recurrence risk. Fusion of prediction scores generated by the two classifiers further improved prediction performance.

Significance: We demonstrated a new approach that has potential to assist clinicians in more effectively managing stage I NSCLC patients to reduce cancer recurrence risk.
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http://dx.doi.org/10.1109/TBME.2015.2477688DOI Listing
May 2016

High incidence of EGFR mutations in pneumonic-type non-small cell lung cancer.

Medicine (Baltimore) 2015 Feb;94(8):e540

From the Department of Cardiothoracic Surgery, the First Affiliated Hospital of Guangzhou Medical University (JL, JS, CY, PH, YG, WL, JH); Guangzhou Institute of Respiratory Disease and China State Key Laboratory of Respiratory Disease (JL, JS, CY, PH, YG, WL, JH); Department of Pathology (PH); and Department of Radiology, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China (YG).

To retrospectively identify computed tomography (CT) features that correlate with epidermal growth factor receptor (EGFR) mutation in surgically resected pneumonic-type lung cancer (P-LC). A total of 953 consecutive patients with surgically resected lung cancer in the First Affiliated Hospital of Guangzhou Medical University from August 2011 to August 2013 were studied. The CT manifestations were reevaluated independently by 2 radiologists. The presence of pneumonic-type consolidation with pathological confirmed non-small lung cancer (NSCLC) was defined as P-LC. EGFR mutation was determined by direct DNA sequencing or amplification refractory mutation system-PCR. EGFR mutation rates as well as clinical and pathological manifestations between P-LC and control lung cancer patients were compared. P-LC was diagnosed in 85 patients. Among these patients, 82 were adenocarcinoma (including 78 cases of invasive adenocarcinoma and 4 cases of microinvasive adenocarcinoma), 2 were squamous carcinoma and 1 was other type. P-LC occurred more frequently in female (58.8% vs 37.1%, P < 0.01), nonsmoking (76.5% vs 56.5%, P = 0.001) and adenocarcinoma (58.8% vs 37.1%, P < 0.01) patients. Moreover, EGFR mutations were found in 39 of 52 P-LC patients (75%) and 263 of 542 non-P-LC NSCLC patients (48.5%). However, no difference was found on the mutation sites of EGFR. Histological type, sex, and radiological manifestations (P-LC vs non-P-LC) but not smoking or sequencing method can be served as the independent predictor of EGFR mutations. P-LC patients showed a significant higher incidence of EGFR mutations, which was independent of sex, histological type, and smoking history. The patients with imaging manifestation of pneumonic-type consolidation are highly suggested to perform EGFR mutation analysis to guide the sequential treatment.
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http://dx.doi.org/10.1097/MD.0000000000000540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4554154PMC
February 2015

Immune reconstitution from peripheral blood mononuclear cells inhibits lung carcinoma growth in NOD/SCID mice.

Oncol Lett 2014 Oct 24;8(4):1638-1644. Epub 2014 Jul 24.

Department of Cardiothoracic Surgery, Guangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical College, Guangzhou, Guangdong 510120, P.R. China.

Drug resistance and immune deficiency are important factors for the poor prognosis of lung carcinoma. The present study explored the possible protective effect of immune reconstitution from peripheral blood mononuclear cells (PBMCs) on multi-drug-resistant human lung carcinoma Am1010 cells in non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice. The inoculated tumor fragments grew rapidly in the NOD/SCID mice. The growth was significantly inhibited by intraperitoneal injection of PBMCs. In the mice injected with PBMCs, numerous CD3 and CD8 cells, but less CD4 cells, were found in spleen and tumor tissues. These data suggest that PBMC transplantation inhibits lung carcinoma progression via the reconstitution of the immune system, particularly of cytotoxic T lymphocytes.
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http://dx.doi.org/10.3892/ol.2014.2379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4156269PMC
October 2014

Askin tumor: CT and FDG-PET/CT imaging findings and follow-up.

Medicine (Baltimore) 2014 Jul;93(6):e42

Department of Radiology (TX, YG, JL), The First Affiliated Hospital of GuangZhou Medical University, Guangzhou, 510120; Department of Radiology (YC), State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, 510060, PR China.

The aim of the study was to describe the imaging findings of Askin tumors on computed tomography (CT) and fluorine 18 fluorodeoxyglucose-positron emission tomography (FDG-PET/CT).Seventeen cases of Askin tumors confirmed by histopathology were retrospectively analyzed in terms of CT (17 cases) and FDG-PET/CT data (6 cases).Fifteen of the tumors were located in the chest wall and the other 2 were in the anterior middle mediastinum. Of the 15 chest wall cases, 13 demonstrated irregular, heterogeneous soft tissue masses with cystic degeneration and necrosis, and 2 demonstrated homogeneous soft tissue masses on unenhanced CT scans. Two mediastinal tumors demonstrated the irregular, heterogeneous soft tissue masses. Calcifications were found in 2 tumors. The tumors demonstrated heterogeneously enhancement in 16 cases and homogeneous enhancement in 1 case on contrast-enhanced scans. FDG-PET/CT images revealed increased metabolic activity in all 6 cases undergone FDG-PET/CT scan, and the lesion SUVmax ranged from 4.0 to 18.6. At initial diagnosis, CT and FDG-PET/CT scans revealed rib destruction in 9 cases, pleural effusion in 9 cases, and lung metastasis in 1 case. At follow-up, 12 cases showed recurrence and/or metastases, 4 cases showed improvement or remained stable, and 1 was lost to follow-up.In summary, CT and FDG-PET/CT images of Askin tumors showed heterogeneous soft tissue masses in the chest wall and the mediastinum, accompanied by rib destruction, pleural effusion, and increased FDG uptake. CT and FDG-PET/CT imaging play important roles in the diagnosis and follow-up of patients with Askin tumors.
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http://dx.doi.org/10.1097/MD.0000000000000042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4602428PMC
July 2014

Juxta-vascular nodule segmentation based on flow entropy and geodesic distance.

IEEE J Biomed Health Inform 2014 Jul 29;18(4):1355-62. Epub 2014 Jan 29.

Computed aided diagnosis of lung CT data is a new quantitative analysis technique to distinguish malignant nodules from benign ones. Nodule growth rate is a key indicator to discriminate between benign and malignant nodules. Accurate nodule segmentation is the essential for calculating the nodule growth rate. However, it is difficult to segment juxta-vascular nodules, due to the similar gray levels in nodule and attached blood vessels. To distinguish the nodule region from the adjacent vessel region, a flowing direction feature, referred to as the direction of the normal vector for a pixel, is introduced. Since blood is flowing in one single direction through a vessel, the normal vectors of pixels in the vessel region typically point in similar orientations while the directions of those in the nodule region can be viewed as disorganized. The entropy value of the flowing direction features in a neighboring region for a vessel pixel is smaller than that for a nodule pixel. Moreover, vessel pixels typically have a larger geodesic distance to the nodule center than nodule pixels. Based on k -means clustering method, the flow entropy, combined with the geodesic distance, is used to segment vessel attached nodules. The validation of the proposed segmentation algorithm was carried out on juxta-vascular nodules, identified in the Chinalung-CT screening trial and on Lung Image Database Consortium (LIDC) dataset. In fully automated mode, accuracies of 92.9% (26/28), 87.5%(7/8), and 94.9% (149/157) are reached for the outlining of juxta-vascular nodules in the Chinalung-CT, and the first and second datasets of LIDC, respectively. Furthermore, it is demonstrated that the proposed method has low time complexity and high accuracies.
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http://dx.doi.org/10.1109/JBHI.2014.2303511DOI Listing
July 2014

Primary small cell neuroendocrine carcinoma of the mediastinum: computed tomography and histopathological correlation.

J Comput Assist Tomogr 2014 Mar-Apr;38(2):174-8

From the *Department of Radiology, The First Affiliated Hospital, Guangzhou Medical University; †State Key Laboratory of Oncology in South China, Department of Radiology, Cancer Center, Sun Yat-sen University; and ‡Department of Pathology, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China.

Objectives: The objectives of this study were to describe the computed tomographic (CT) and histopathological characteristics of neuroendocrine carcinomas of the mediastinum and to improve the diagnostic accuracy for these tumors.

Materials And Methods: We retrospectively analyzed 9 patients with histopathologically confirmed primary small cell neuroendocrine carcinoma of the mediastinum.

Results: Of the 9 tumors, 6 (67%) were located in the anterior-middle mediastinum; 2, in the anterior-middle-posterior mediastinum; and 1, in the middle-mediastinum. Eight tumors appeared inhomogeneous on CT, with large areas of necrosis, whereas 1 tumor had a uniform density. Four tumors (44%) had scattered punctate calcifications. Moderate, heterogeneous enhancement (range, 21-34 Hounsfield units) was present in 8 patients. All tumors compressed or invaded the adjacent mediastinal structures. Hematoxylin and eosin staining results revealed small tumor cells, with little cytoplasm, pale chromatin, and inconspicuous or absent nucleoli. Immunohistochemical analysis results showed that the tumor cells were positive for chromogranin A, synaptophysin, and neuron-specific enolase.

Conclusions: A large tumor located in the anterior-middle mediastinum, showing scattered punctate calcifications and compressing or invading the adjacent mediastinal structures, should arouse suspicion for a small cell neuroendocrine carcinoma. However, the diagnosis of such tumors requires a combination of pathological and immunohistochemical examination.
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http://dx.doi.org/10.1097/RCT.0b013e3182ab21feDOI Listing
May 2014

The efficacy of the inhalation of an aerosolized Group A streptococcal preparation in the treatment of lung cancer.

Chin J Cancer Res 2012 Dec;24(4):346-52

Department of Cardiothoracic Surgery, The First Affiliated Hospital of Guangzhou Medical College, Guangzhou, China; ; Guangzhou Institute of Respiratory Disease & China State Key Laboratory of Respiratory Disease, Guangzhou, China;

Objective: To observe the efficacy of the inhalation of an aerosolized group A streptococcal (GAS) preparation in treating orthotopic lung cancer in mouse models and assess the feasibility, safety, and effectiveness of this administration mode for lung cancer.

Methods: Lewis lung carcinoma (LLC) cell strains were administered via intrathoracic injection to establish orthotopic lung cancer mouse models. After the tumor-bearing models were successfully established, as confirmed by computed tomography, the mice were administered by inhalation with an aerosolized GAS preparation (GAS group) or aerosolized normal saline (control group). The anti-tumor effect of the aerosolized GAS preparation was evaluated histologically; meanwhile, the survival and quality of life were compared between these two groups.

Results: The aerosolized GAS preparation showed remarkably anti-tumor effect, causing the necrosis of the orthotopic lung cancer cells in tumor-bearing mice. Furthermore, mice in the GAS group had significantly better quality of life and longer survival than those in control group.

Conclusions: The inhalation of aerosolized GAS preparation may be a feasible, safe and effective solution for lung cancer.
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http://dx.doi.org/10.3978/j.issn.1000-9604.2012.10.08DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3551315PMC
December 2012

Computed tomography appearance of inflammatory myofibroblastic tumor in the mediastinum.

J Comput Assist Tomogr 2012 Nov-Dec;36(6):654-8

Department of Radiology, The First Affiliated Hospital, Guangzhou Medical College, Guangzhou, PR China.

Objective: This study aimed to improve the diagnosis of inflammatory myofibroblastic tumor (IMT) in the mediastinum by analysis of computed tomographic (CT) images.

Materials And Methods: Clinical data, CT, and pathological findings of 6 patients diagnosed with IMT in the mediastinum were retrospectively analyzed.

Results: Of the 6 patients, 5 were women, and mean age at diagnosis was 34 years. All the lesions were solid soft tissue masses and ranged in maximum diameter from 5.0 to 8.5 cm, which were located in the anterior (n = 1), middle (n = 2), and posterior mediastinum (n = 3). The anterior mediastinal tumor had a clear boundary. The tumors in the middle mediastinum had indistinct boundaries: one was invading the right wall of the trachea and the other was invading the esophageal wall. A tumor located in the right posterior mediastinum caused osteolysis of the adjacent ribs. A small amount of calcification was seen in the tumor in the right posterior-inferior mediastinum. After administration of contrast, all tumors showed varying degrees of contrast enhancement (range, 17-47 HU) on chest CT scan. Recurrence occurred in only 1 case.

Conclusions: The common CT appearance of IMT in the mediastinum is as a soft tissue mass with uniform density. All tumors show varying degrees of contrast enhancement. Some lesions have clear boundaries; others do not. Computed tomography examination can help to determine the areas involved by lesions and their relationships with adjacent tissues, which facilitates the prediction of the likely surgical requirements.
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http://dx.doi.org/10.1097/RCT.0b013e31826801baDOI Listing
February 2013

Establishment of an orthotopic lung cancer model in nude mice and its evaluation by spiral CT.

J Thorac Dis 2012 Apr;4(2):141-5

Objective: To establish a simple and highly efficient orthotopic animal model of lung cancer cell line A549 and evaluate the growth pattern of intrathoracic tumors by spiral CT.

Methods: A549 cells (5×10(6) mL(-1)) were suspended and inoculated into the right lung of BALB/c nude mice via intrathoracic injection. Nude mice were scanned three times each week by spiral CT after inoculation of lung cancer cell line A549. The survival time and body weight of nude mice as well as tumor invasion and metastasis were examined. Tissue was collected for subsequent histological assay after autopsia of mice.

Results: The tumor-forming rate of the orthotopic lung cancer model was 90%. The median survival time was 30.7 (range, 20-41) days. The incidence of tumor metastasis was 100%. The mean tumor diameter and the average CT value gradually increased in a time-dependent manner.

Conclusions: The method of establishing the orthotopic lung cancer model through transplanting A549 cells into the lung of nude mice is simple and highly successful. Spiral CT can be used to evaluate intrathoracic tumor growth in nude mice vividly and dynamically.
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http://dx.doi.org/10.3978/j.issn.2072-1439.2012.03.04DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3378238PMC
April 2012

Pulmonary alveolar proteinosis: quantitative CT and pulmonary functional correlations.

Eur J Radiol 2012 Sep 28;81(9):2430-5. Epub 2011 May 28.

Department of Radiology, the First Affiliated Hospital of Guangzhou Medical College, Guangzhou 510120, China.

Objective: We assessed the relationship between quantitative computer tomography (qCT) and the pulmonary function test (PFT) or blood gas analysis in pulmonary alveolar proteinosis (PAP) patients, as well as the utility of these analyses to monitor responses to whole lung lavage (WLL) therapy.

Methods: Thirty-eight PAP patients simultaneously received a CT scan and PFT. Fifteen of these patients, undergoing sequential WLL for a total of 20 lavages, also underwent chest CT scans and blood gas analysis before and after WLL, and 14 of 15 patients underwent simultaneous PFT analysis. Differences between the qCT and PFT results were analyzed by canonical correlation.

Results: PAP patients with low predicted values for FVC, FEV1, D(LCO) and D(LCO)/VA indicated small airspace volume and mean lung inflation, low airspace volume/total lung volume ratio and high mean lung density. Correlation and regression analysis revealed a strong correlation between D(LCO) and PaO(2) values with CT results. The qCT results indicated that WLL significantly decreased lung weights and mean lung densities, and improved the total airspace volume/total lung volume ratios and mean lung inflations.

Conclusion: Quantitative CT may be a sensitive tool for measuring the response of PAP patients to medical interventions such as WLL.
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http://dx.doi.org/10.1016/j.ejrad.2011.05.005DOI Listing
September 2012

Video-assisted thoracoscopic surgery (VATS) for patients with solitary fibrous tumors of the pleura.

J Thorac Oncol 2010 Feb;5(2):240-3

Department of Cardiothoracic Surgery, The First Affiliated Hospital of Guangzhou Medical College, Guangzhou, People's Republic of China.

Objectives: To present our experience of video-assisted thoracoscopic surgery (VATS) for patients with solitary fibrous tumors of the pleura (SFTPs) and to discuss the treatment of choice of such neoplasms.

Methods: Between June 2000 and September 2008, 21 patients with SFTPs (9 men and 12 women) underwent VATS at our department. The mean age was 52.5 years (range, 33-76 years).

Results: Surgical excision was performed in all patients. Surgical excision was performed by VATS in 15 patients (71.4%), by VATS plus a small thoracotomy (<5 cm) in 4 patients (19.0%), and by posterolateral thoracotomy accompanied by VATS in 2 patients (9.5%). Mean chest drain duration was 2.3 days (range, 1-4 days), and the mean hospital stay was 7.2 days (range, 4-15 days). There were 18 pathologically benign SFTP cases (85.7%) and 3 malignant SFTP cases (14.3%). There was no operative morbidity or mortality. No recurrence or metastasis of SFTPs developed during postoperative median follow-up period of 43 months.

Conclusions: Complete resection and close follow-up for years after operation is recommended for SFTPs. VATS may play an important role in reducing the size of the thoracotomy incision in the treatment of SFTPs, which results in less invasive surgery.
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http://dx.doi.org/10.1097/JTO.0b013e3181c6b6b2DOI Listing
February 2010

Gemcitabine plus cisplatin chemotherapy with concurrent para-toluenesulfonamide local injection therapy for peripherally advanced nonsmall cell lung cancer larger than 3 cm in the greatest dimension.

Anticancer Drugs 2009 Oct;20(9):838-44

Guangzhou Institute of Respiratory Diseases, First Affiliated Hospital of Guangzhou Medical College, Guangzhou, China.

Para-toluenesulfonamide (PTS), active ingredient being PTS, is a new anticancer drug applied through local intratumoral injection. The aim of this phase II clinical trial was to investigate the response and toxicity of standard gemcitabine (GEM) plus cisplatin (CIS) chemotherapy with concurrent intratumoral injection of PTS in peripherally advanced nonsmall cell lung cancer. Patients received 1250 mg/m of GEM on day 1, 8, and 75 mg/m of CIS on day 1, every 21 days for four cycles. PTS was injected intratumorally through percutaneous injection under computed tomography guidance on days 5, 12, 15, and 18 of cycle 1, and repeated on days 5 and 12 of cycle 2 if a less than 50% necrotic area was achieved after the first cycle according to the computed tomography scan. Twelve (46.2%) patients had metastatic disease, whereas 14 (53.8%) patients had stage IIIB disease. All 26 patients were assessable for response. Overall response rate by intention-to-treat was 53.8% (95% confidence interval: 34.6-73.0%). Median progression-free survival and overall survival were 6.5 months (95% confidence interval: 3.8-10.2 months) and 14.5 months (10.0-18.0 months), respectively. One-year and 2-year survivals were 57.7 and 22.4%, respectively. The grade 3-4 hematologic adverse events were neutropenia in six patients (23.1%), anemia in three (11.5%), and thrombocytopenia in four patients (15.4%). Nonhematologic toxicities were generally mild and usually not dose-limiting. Although grade 1-2 emesis occurred in nine patients (34.6%), only one had grade 3 vomiting. Grade 1-2 cough, local pain, and peripheral neurotoxocity developed in 12 (46.2%), three (11.5%), and five (19.2%) patients, respectively. There were no treatment-related deaths. GEM/CIS chemotherapy with concurrent PTS local injection therapy is a well-tolerated modality with potential activity in previously untreated peripheral advanced nonsmall cell lung cancer patients.
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http://dx.doi.org/10.1097/CAD.0b013e32832fe48fDOI Listing
October 2009