Predicting resection margin status of pancreatic neuroendocrine tumors on CT: performance of NCCN resectability criteria.

OBJECTIVE: To test the performance of the National Comprehensive Cancer Network (NCCN) CT resectability criteria for predicting the surgical margin status of pancreatic neuroendocrine tumor (PNET) and to identify factors associated with margin-positive resection. METHODS: Eighty patients with pre-operative CT and upfront surgery were retrospectively enrolled. Two radiologists assessed the CT resectability (resectable [R], borderline resectable [BR], unresectable [UR]) of the PNET according to NCCN criteria. Logistic regression was used to identify factors associated with resection margin status. κ statistics were used to evaluate interreader agreements. Kaplan-Meier method with log-rank test was used to estimate and compare recurrence-free survival (RFS). RESULTS: Forty-five patients (56.2%) received R0 resection and 35 (43.8%) received R1 or R2 resection. R0 resection rates were 63.6-64.2%, 20.0-33.3%, and 0% for R, BR, and UR diseases, respectively (all p ≤ 0.002), with a good interreader agreement (κ, 0.74). Tumor size (<2 cm, 2-4 cm, and >4 cm; odds ratio (OR), 9.042-18.110; all p ≤ 0.007) and NCCN BR/UR diseases (OR, 5.918; p = 0.032) were predictors for R1 or R2 resection. The R0 resection rate was 91.7% for R disease <2 cm and decreased for larger R disease. R0 resection and smaller tumor size in R disease improved RFS. CONCLUSION: NCCN resectability criteria can stratify patients with PNET into distinct groups of R0 resectability. Adding tumor size to R disease substantially improves the prediction of R0 resection, especially for PNETs <2 cm. ADVANCES IN KNOWLEDGE: Tumor size and radiologic resectability independently predicted margin status of PNETs.

Nicotinamide (niacin) supplement increases lipid metabolism and ROS-induced energy disruption in triple-negative breast cancer: potential for drug repositioning as an anti-tumor agent.

Metabolic dysregulation is an important hallmark of cancer. Nicotinamide (NAM), a water-soluble amide form of niacin (vitamin B3), is currently available as a supplement for maintaining general physiologic functions. NAM is a crucial regulator of mitochondrial metabolism and redox reactions. In this study, we aimed to identify the mechanistic link between NAM-induced metabolic regulation and the therapeutic efficacy of NAM in triple-negative breast cancer (TNBC). The combined analysis using multiomics systems biology showed that NAM decreased mitochondrial membrane potential and ATP production, but increased the activities of reverse electron transport (RET), fatty acid ß-oxidation and glycerophospholipid/sphingolipid metabolic pathways in TNBC, collectively leading to an increase in the levels of reactive oxygen species (ROS). The increased ROS levels triggered apoptosis and suppressed tumour growth and metastasis of TNBC in both human organoids and xenograft mouse models. Our results showed that NAM treatment leads to cancer cell death in TNBC via mitochondrial dysfunction and activation of ROS by bifurcating metabolic pathways (RET and lipid metabolism); this provides insights into the repositioning of NAM supplement as a next-generation anti-metabolic agent for TNBC treatment.

Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma: Radiologic and Clinical Factors Predictive of Survival.

OBJECTIVE. The goal of this study was to evaluate radiologic and clinical factors associated with overall survival of advanced hepatocellular carcinoma treated with hepatic arterial infusion chemotherapy (HAIC). MATERIALS AND METHODS. This single-center retrospective study included 180 patients with advanced hepatocellular carcinoma who underwent HAIC with a 5-fluorouracil (250-500 mg/m2 for 5 hours) plus cisplatin (10-20 mg/m2 for 1-2 hours) regimen via an implantable port system. Survival curves were generated by the Kaplan-Meier method and compared by log-rank tests. Factors associated with overall survival were evaluated with Cox proportional hazard models. RESULTS. The median overall survival time was 7.6 months (95% CI, 6.1-9.1), and the objective response rate was 15%. In multivariate analysis, infiltrative tumor growth (hazard ratio [HR], 1.002; p = .03) and rimlike arterial enhancement (HR, 3.040; p < .001) were pretreatment radiologic factors associated with reduced overall survival. No early response to treatment (HR, 2.064-6.491) and higher Child-Pugh class (HR, 2.010-2.815) were strong prognostic factors of poor outcome. Treatment with three or more HAIC cycles (HR, 0.371; p = .001) and high-dose HAIC (HR, 0.447; p < .001) were favorable for increased overall survival. CONCLUSION. Infiltrative tumor growth and rimlike arterial enhancement in pre-treatment imaging studies were associated with poor prognosis, and better early radiologic response and preserved liver function reserve were strong indicators of prolonged survival. Recognizing these radiologic and clinical predictors may help optimize care of patients with hepatocellular carcinoma.

Gadoxetate-enhanced dynamic contrast-enhanced MRI for evaluation of liver function and liver fibrosis in preclinical trials.

BACKGROUND: To facilitate translational drug development for liver fibrosis, preclinical trials need to be run in parallel with clinical research. Liver function estimation by gadoxetate-enhanced dynamic contrast-enhanced MRI (DCE-MRI) is being established in clinical research, but still rarely used in preclinical trials. We aimed to evaluate feasibility of DCE-MRI indices as translatable biomarkers in a liver fibrosis animal model. METHODS: Liver fibrosis was induced in Sprague-Dawley rats by thioacetamide (200 mg, 150 mg, and saline for the high-dose, low-dose, and control groups, respectively). Subsequently, DCE-MRI was performed to measure: relative liver enhancement at 3-min (RLE-3), RLE-15, initial area-under-the-curve until 3-min (iAUC-3), iAUC-15, and maximum-enhancement (Emax). The correlation coefficients between these MRI indices and the histologic collagen area, indocyanine green retention at 15-min (ICG-R15), and shear wave elastography (SWE) were calculated. Diagnostic performance to diagnose liver fibrosis was also evaluated by receiver-operating-characteristic (ROC) analysis. RESULTS: Animal model was successful in that the collagen area of the liver was the largest in the high-dose group, followed by the low-dose group and control group. The correlation between the DCE-MRI indices and collagen area was high for iAUC-15, Emax, iAUC-3, and RLE-3 but moderate for RLE-15 (r, - 0.81, - 0.81, - 0.78, - 0.80, and - 0.51, respectively). The DCE-MRI indices showed moderate correlation with ICG-R15: the highest for iAUC-15, followed by iAUC-3, RLE-3, Emax, and RLE-15 (r, - 0.65, - 0.63, - 0.62, - 0.58, and - 0.56, respectively). The correlation coefficients between DCE-MRI indices and SWE ranged from - 0.59 to - 0.28. The diagnostic accuracy of RLE-3, iAUC-3, iAUC-15, and Emax was 100% (AUROC 1.000), whereas those of RLE-15 and SWE were relatively low (AUROC 0.777, 0.848, respectively). CONCLUSION: Among the gadoxetate-enhanced DCE-MRI indices, iAUC-15 and iAUC-3 might be bidirectional translatable biomarkers between preclinical and clinical research for evaluating histopathologic liver fibrosis and physiologic liver functions in a non-invasive manner.

Difference between Right and Left Facial Surface Electromyography in Healthy People.

INTRODUCTION: The study was to see whether there were differences in values of facial surface electromyography in subjects of good heath by muscles, age, and sex. METHODS: It draws ratio between lower value and higher value (R-LV/HV) and asymmetry index (AI), based on root mean square (RMS) from measurement of facial surface electromyography (sEMG) in 154 people of healthy people (male:female = 70:84) aging between more than 20 and less than 70. RESULTS: For R-LV/HV, it averages 81.70±14.60% on frontalis muscle, 73.74±19.12% on zygomaticus muscle, and 79.72±14.77% on orbicularis oris muscle. With analysis of the AI average was 10.87±10.14% on frontalis muscle, 16.71±14.79% on zygomaticus muscle, and 12.10±10.05% on orbicularis oris muscle. Both values were statistically significant in three parts of muscles as shown. Both of R-LV/HV and AI show no statistically significant difference on age and sex (p>0.05). CONCLUSIONS: It could provide basic data for the future diagnosis of facial nerve palsy patients by measuring facial sEMG values for healthy people.

Higher serum interleukin-17A levels as a potential biomarker for predicting early disease progression in patients with hepatitis B virus-associated advanced hepatocellular carcinoma treated with sorafenib.

BACKGROUND: Although sorafenib is the only available drug with proven efficacy for patients with advanced hepatocellular carcinoma (HCC), the clinical efficacy of sorafenib is variable and unpredictable. The aim of the current study was to identify potential serum biomarkers predicting cancer progression and overall survival (OS) in patients with hepatitis B virus (HBV)-related advanced HCC treated with sorafenib. METHODS: Thirty-four patients with HBV-related advanced HCC (modified Union for International Cancer Control [UICC] stage IVa or IVb) treated with sorafenib for more than 4weeks were retrospectively enrolled. Using a Luminex 200 system, 11 cytokines including interleukin-17A (IL-17A) were measured in baseline serum samples prior to sorafenib administration. Several clinical factors and the serum concentrations of the 11 cytokines were analyzed using Cox regression analysis. RESULTS: In the analysis of progression-free survival (PFS), older age (year; hazard ratio [HR]=1.07; 95% confidence interval [CI]=1.00-1.15; P=0.046) and higher baseline serum IL-17A level (>1.94pg/mL; HR=19.96; 95% CI=3.32-119.86; P=0.001) were identified as significant risk factors for early progression with good predictive power (Harrell's C=0.817, standard error estimates (se)=0.085). In the analysis of OS, higher Child-Pugh score (>5; HR=2.35, 95% CI=1.09-5.10, P=0.030) and lower serum baseline fibroblast growth factor-2 level (≤20.57pg/mL; HR=3.24, 95% CI=1.22-8.60, P=0.018) were identified as negative predictive factors for OS, even though the model did not have significant predictive power (Harrell's C=0.634, se=0.062). CONCLUSION: A higher serum IL-17A level is a potential biomarker for predicting poor PFS in patients with HBV-related advanced HCC treated with sorafenib.

Complementary p- and n-type polymer doping for ambient stable graphene inverter.

Graphene offers great promise to complement the inherent limitations of silicon electronics. To date, considerable research efforts have been devoted to complementary p- and n-type doping of graphene as a fundamental requirement for graphene-based electronics. Unfortunately, previous efforts suffer from undesired defect formation, poor controllability of doping level, and subtle environmental sensitivity. Here we present that graphene can be complementary p- and n-doped by simple polymer coating with different dipolar characteristics. Significantly, spontaneous vertical ordering of dipolar pyridine side groups of poly(4-vinylpyridine) at graphene surface can stabilize n-type doping at room-temperature ambient condition. The dipole field also enhances and balances the charge mobility by screening the impurity charge effect from the bottom substrate. We successfully demonstrate ambient stable inverters by integrating p- and n-type graphene transistors, which demonstrated clear voltage inversion with a gain of 0.17 at a 3.3 V input voltage. This straightforward polymer doping offers diverse opportunities for graphene-based electronics, including logic circuits, particularly in mechanically flexible form.