CT-based radiomics for differentiating peripherally located pulmonary sclerosing pneumocytoma from carcinoid.

BACKGROUND: Pulmonary sclerosing pneumocytoma (PSP) and pulmonary carcinoid (PC) are difficult to distinguish based on conventional imaging examinations. In recent years, radiomics has been used to discriminate benign from malignant pulmonary lesions. However, the value of radiomics based on computed tomography (CT) images to differentiate PSP from PC has not been well explored. PURPOSE: We aimed to investigate the feasibility of radiomics in the differentiation between PSP and PC. METHODS: Fifty-three PSP and fifty-five PC were retrospectively enrolled and then were randomly divided into the training and test sets. Univariate and multivariable logistic analyses were carried to select clinical predictor related to differential diagnosis of PSP and PC. A total of 1316 radiomics features were extracted from the unenhanced CT (UECT) and contrast-enhanced CT (CECT) images, respectively. The minimum redundancy maximum relevance and the least absolute shrinkage and selection operator were used to select the most significant radiomics features to construct radiomics models. The clinical predictor and radiomics features were integrated to develop combined models. Two senior radiologists independently categorized each patient into PSP or PC group based on traditional CT method. The performances of clinical, radiomics, and combined models in differentiating PSP from PC were investigated by the receiver operating characteristic (ROC) curve. The diagnostic performance was also compared between the combined models and radiologists. RESULTS: In regard to differentiating PSP from PC, the area under the curves (AUCs) of the clinical, radiomics, and combined models were 0.87, 0.96, and 0.99 in the training set UECT, and were 0.87, 0.97, and 0.98 in the training set CECT, respectively. The AUCs of the clinical, radiomics, and combined models were 0.84, 0.92, and 0.97 in the test set UECT, and were 0.84, 0.93, and 0.98 in the test set CECT, respectively. In regard to the differentiation between PSP and PC, the combined model was comparable to the radiomics model, but outperformed the clinical model and the two radiologists, whether in the test set UECT or CECT. CONCLUSIONS: Radiomics approaches show promise in distinguishing between PSP and PC. Moreover, the integration of clinical predictor (gender) has the potential to enhance the diagnostic performance even further.

Differentiating Peripherally Located Pulmonary Noncalcified Hamartoma From Carcinoid Using CT Radiomics Approaches.

OBJECTIVE: This article aimed to differentiate noncalcified hamartoma from pulmonary carcinoid preoperatively using computed tomography (CT) radiomics approaches. MATERIALS AND METHODS: The unenhanced CT (UECT) and contrast-enhanced CT (CECT) data of noncalcified hamartoma (n = 73) and pulmonary carcinoid (n = 54; typical/atypical carcinoid = 13/41) were retrospectively analyzed. The patients were randomly divided into the training and validation sets. A total of 396 radiomics features were extracted from UECT and CECT, respectively. The features were selected by using the minimum redundancy maximum relevance and the least absolute shrinkage and selection operator to construct a radiomics model. Clinical factors and radiomics features were integrated to build a nomogram model. The performance of clinical factors, radiomics, and nomogram models on the differential diagnosis between noncalcified hamartoma and carcinoid were investigated. Diagnostic performance of radiologists was also explored. RESULT: In regard to distinguishing noncalcified hamartoma from carcinoid, the areas under the receiver operating characteristic curves of the clinical, radiomics, and nomogram models were 0.88, 0.94, and 0.96 in the training set UECT, and were 0.85, 0.92, and 0.96 in the training set CECT, respectively. The areas under the curve of the 3 models were 0.89, 0.96, and 0.96 in the validation set UECT, and were 0.79, 0.90, and 0.94 in the validation set CECT, respectively. The nomogram model exhibited good calibration and was clinically useful by decision curve analysis. Nomogram did not show significant improvement compared with radiomics, neither for UECT nor for CECT. Diagnostic performance of radiologists was lower than both radiomics and nomogram model. CONCLUSIONS: Radiomics approaches may be useful in distinguishing peripheral pulmonary noncalcified hamartoma from carcinoid. Radiomics features extracted from CECT provided no significant benefit when compared with UECT.

Can CT Radiomics Detect Acquired T790M Mutation and Predict Prognosis in Advanced Lung Adenocarcinoma With Progression After First- or Second-Generation EGFR TKIs?

Objective: To explore the potential of CT radiomics in detecting acquired T790M mutation and predicting prognosis in patients with advanced lung adenocarcinoma with progression after first- or second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy. Materials and Methods: Contrast-enhanced thoracic CT was collected from 250 lung adenocarcinoma patients (with acquired T790M mutation, n = 146, without mutation, n = 104) after progression on first- or second-generation TKIs. Radiomic features were extracted from each volume of interest. The maximum relevance minimum redundancy and the least absolute shrinkage and selection operator (LASSO) regression method were used to select the optimized features in detecting acquired T790M mutation. Univariate Cox regression and LASSO Cox regression were used to establish the radiomics model to predict the progression-free survival of osimertinib treatment. Finally, nomograms (which) combined clinical factors with radscore to predict the acquired T790M mutation and prognosis were built separately. In addition, the two nomograms were validated by the concordance index (C-index), decision curve analysis (DCA), and calibration curve analysis where appropriate. Results: Clinical factors including the progression-free survival of first-line EGFR TKIs, EGFR mutation, and N stage and 12 radiomic features were useful in predicting the acquired T790M mutation. The area under the receiver operating characteristic curves (AUC) of clinical, radiomics, and nomogram models were 0.70, 0.74, and 0.78 in the training set and 0.71, 0.71, and 0.76 in the validation set, respectively. The DCA and calibration curve analysis demonstrated a good performance of the nomogram model. Clinical factors including age and first-generation EGFR TKIs and 12 radiomic features were useful in patients' outcome prediction. The C-index of the combined nomogram was 0.686 in the training set and 0.630 in the validation set, respectively. Calibration curves demonstrated a relatively poor performance of the nomogram model. Conclusion: Nomogram combined clinical factors with radiomic features might be helpful to detect whether patients developed acquired T790M mutation or not after progression on first- or second-generation EGFR TKIs. Nomogram prognostic model combined clinical factors with radiomic features might have a limited value in predicting the survival of patients harboring acquired T790M mutation treated with osimertinib.

Resveratrol Improves Liver Steatosis and Insulin Resistance in Non-alcoholic Fatty Liver Disease in Association With the Gut Microbiota.

Resveratrol (RSV) is a potential alternative therapy for non-alcoholic fatty liver disease (NAFLD) that has been evaluated in many clinical trials, but the mechanisms of RSV action have not been fully elucidated. Recent studies suggested that the gut microbiota is an important RSV target; therefore, we speculated that the gut microbiota might mediate the beneficial effects of RSV in NAFLD. To verify this hypothesis, we established a high-fat diet (HFD)-induced NAFLD mouse model, which was subjected to RSV gavage to evaluate the therapeutic effects. We observed that RSV reduced liver steatosis and insulin resistance in NAFLD. RSV significantly changed the diversity and composition of the gut microbiota according to 16S rRNA sequencing. Gut microbiota gene function prediction showed that the enrichment of pathways related to lipid and glucose metabolism decreased after RSV treatment. Furthermore, correlation analysis indicated that the improvements in NAFLD metabolic indicators were closely related to the altered gut microbiota. We further fermented RSV with the gut microbiota in vitro to verify that RSV directly affected the gut microbiota. Our data suggested that the gut microbiota might be an important target through which RSV exerts its anti-NAFLD effect.

Hepatitis B virus X protein promotes liver cell pyroptosis under oxidative stress through NLRP3 inflammasome activation.

OBJECTIVE: Hepatitis B virus X protein (HBx) is a pivotal factor for HBV-induced hepatitis. Herein, we sought to investigate HBx-mediated NLR pyrin domain containing 3 (NLRP3) inflammasome activation and pyroptosis under oxidative stress. METHODS: The effect of HBx on the NLRP3 inflammasome was analyzed by enzyme-linked immunosorbent assays, quantitative reverse transcription-polymerase chain reaction, western blotting, and immunofluorescence in hepatic HL7702 cells. Pyroptosis was evaluated by western blotting, lactate dehydrogenase release, propidium iodide staining, and transmission electron microscopy. NLRP3 expression in the inflammasome from liver tissues was assessed by immunohistochemistry. RESULTS: In hydrogen peroxide (H2O2)-stimulated HL7702 cells, HBx triggered the release of pro-inflammatory mediators apoptosis-associated speck-like protein containing a CARD (ASC), interleukin (IL)-1ß, IL-18, and high-mobility group box 1 (HMGB1); activated NLRP3; and initiated pro-inflammatory cell death (pyroptosis). HBx localized to the mitochondria, where it induced mitochondrial damage and production of mitochondrial reactive oxygen species (mitoROS). Treatment of HL7702 cells with a mitoROS scavenger attenuated HBx-induced NLRP3 activation and pyroptosis. Expression levels of NLRP3, ASC, and IL-1ß in liver tissues from patients were positively correlated with HBV DNA concentration. CONCLUSIONS: The NLRP3 inflammasome was activated by elevated mitoROS levels and mediated HBx-induced liver inflammation and hepatocellular pyroptosis under H2O2-stress conditions.

12-Lipoxygenase promotes epithelial-mesenchymal transition via the Wnt/ß-catenin signaling pathway in gastric cancer cells.

BACKGROUND: 12-Lipoxygenase (12-LOX) plays a major role in the progression and metastasis of various types of cancer. In gastric cancer (GC), the expression level of 12-LOX is significantly up-regulated; however, its function, and underlying mechanism of action remain unclear. METHODS: The mRNA and protein expression levels of 12-LOX were assessed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analyses, respectively, in GC cell lines. 12-LOX expression was stably up-regulated using lentiviral vector in BGC823 and MGC803 cells, and cell-counting kit-8 (CCK8), colony formation, and invasion assays were performed to verify the function of 12-LOX in proliferation and metastasis. In addition, the expression levels of epithelial-mesenchymal transition (EMT) differentiation markers and downstream targets of the Wnt/ß-catenin signaling pathway were examined by Western blotting. A nude mouse model of tumor growth and metastasis was established to investigate the role of 12-LOX in vivo. RESULTS: Our findings demonstrate that 12-LOX mRNA and protein were highly expressed in GC cell lines. 12-LOX overexpression promoted GC cell proliferation, migration, and invasion both in vitro and in vivo. In addition, up-regulation of 12-LOX promoted the EMT in GC cells, as reflected by a decrease in E-cadherin expression and an increase in N-cadherin and Snail expression. 12-LOX overexpression in GC cells also increased the expression of multiple downstream targets of the Wnt/ß-catenin signaling pathway. CONCLUSION: These findings revealed that 12-LOX functions as an oncogene in promoting GC cell proliferation and metastasis in vitro and in vivo. In addition, 12-LOX might regulate the EMT via the Wnt/ß-catenin signaling pathway, indicating a potential role for 12-LOX as a target in GC treatment.

Diffuse hepatic epithelioid hemangioendothelioma with multiple splenic metastasis and delayed multifocal bone metastasis after liver transplantation on FDG PET/CT images: A case report.

RATIONALE: Malignant hepatic epithelioid hemangioendotheliom (HEH) is a rare vascular tumor of endothelial origin, with multiple metastases to the spleen. This report describes a diffuse HEH with splenic metastasis on 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) images and delayed mutifocal bone metastasis after liver transplantation (LTx). PATIENT CONCERNS: A 30-year-old male was admitted to our hospital with a complaint of abdominal distension, fatigue, and anorexia for 2 months. DIAGNOSES: Mild to moderate FDG uptake in the whole liver, and multifocal FDG uptake in the spleen were observed on 18F-FDG PET/CT scan. Ultrasound guided liver biopsy was performed, and a diagnosis of HEH was confirmed. INTERVENTIONS: The patient underwent LTx and splenectomy. OUTCOMES: The patient developed low back pain due to unknown etiology, 3 months after surgery. A follow-up 18F-FDG PET/CT scan demonstrated multifocal bone destruction. Unfortunately, the patient died 12 months after surgery. LESSONS: It is noteworthy that despite liver transplantation for the treatment of HEH, there may be a risk of recurrence. For these patients with extrahepatic lesions, adjuvant chemotherapy may be a useful alternative treatment method for the prevention of recurrence.

[PET-CT imaging features of primary ureteric lymphoma: A case report and literature review].

OBJECTIVE: To review the dual-time-point 18F-fluorodeoxyglucose (FDG) positron emission tomography/X-ray computed tomography (PET-CT) imaging for a patient with primary ureteric lymphoma (PUL), and explore the potential of FDG PET-CT on diagnosis, staging and evaluation of treatment in patients with PUL.
 Methods: Complete clinical and imaging data of one patient with PUL was reported. The relevant literatures from 1997 to 2016 were reviewed, and the imaging features of uriteric lymphoma were analyzed.
 Results: The patient presented with microhematuria, a soft-density mass with moderate enhancement in the mid left ureter, and a luminal stenosis with the scope inserted 5 cm into the left stoma, but no mass was found. The patient was pathologically diagnosed as follicular lymphoma (stage IE confirmed by whole body FDG PET-CT).
 Conclusion: PET-CT may be useful in diagnosis, clinical stage and therapy assessment in patients with PUL.