Preceding infection or inflammation such as bacterial meningitis has been associated with poor outcomes after stroke. Previously, we reported that intracorpus callosum microinjection of lipopolysaccharides (LPS) strongly accelerated the ischemia/reperfusion-evoked brain tissue damage via recruiting inflammatory cells into the ischemic lesion. Simvastatin, 3-hydroxy-3-methylgultaryl (HMG)-CoA reductase inhibitor, has been shown to reduce inflammatory responses in vascular diseases. Thus, we investigated whether simvastatin could reduce the LPS-accelerated ischemic injury. Simvastatin (20 mg/kg) was orally administered to rats prior to cerebral ischemic insults (4 times at 72, 48, 25, and 1-h pre-ischemia). LPS was microinjected into rat corpus callosum 1 day before the ischemic injury. Treatment of simvastatin reduced the LPS-accelerated infarct size by 73%, and decreased the ischemia/reperfusion-induced expressions of pro-inflammatory mediators such as iNOS, COX-2 and IL-1beta in LPS-injected rat brains. However, simvastatin did not reduce the infiltration of microglial/macrophageal cells into the LPS-pretreated brain lesion. In vitro migration assay also showed that simvastatin did not inhibit the monocyte chemoattractant protein-1-evoked migration of microglial/macrophageal cells. Instead, simvastatin inhibited the nuclear translocation of NF-kappaB, a key signaling event in expressions of various proinflammatory mediators, by decreasing the degradation of IkappaB. The present results indicate that simvastatin may be beneficial particularly to the accelerated cerebral ischemic injury under inflammatory or infectious conditions.
Animals ; Brain ; Corpus Callosum ; Inflammation ; Lipopolysaccharides ; Macrophages ; Meningitis, Bacterial ; Microglia ; Microinjections ; Monocytes ; NF-kappa B ; Oxidoreductases ; Rats ; Simvastatin* ; Stroke ; Vascular Diseases

PURPOSE: This study evaluated the usefulness of semiquantitative and volumetric PET parameters for predicting prognosis in patients with advanced gastric cancer (AGC).METHODS: We enrolled 213 patients who underwent ¹⁸F-fluoro-2-deoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) prior to curative surgery for AGC. Maximum standardized uptake value (SUVmax) and tumor-to-liver uptake ratio (TLR) were measured in all patients. Metabolic tumor volume (MTV) and total lesion glycolysis were measured in volume-measurable patients. For further quantification of FDG uptake, we developed PET prognostic scores by combining SUVmax and MTV (1: low SUVmax/low MTV; 2: high SUVmax/low MTV; 3: high SUVmax/high MTV). Comparison of PET parameters between recurrence and non-recurrence groups was performed. Univariate and multivariate analyses for recurrence-free survival (RFS) and overall survival (OS) were subsequently performed.RESULTS: The recurrence rate was 32.4% (69/213 patients). Mean SUVmax and mean MTV of the recurrence group were significantly higher than those of the non-recurrence group (p = 0.026 and p = 0.025). TLR showed marginal significance (p = 0.051). In multivariate analysis for RFS including all patients, SUVmax (p = 0.022), TLR (p = 0.010), and PET score (p = 0.003) were independent prognostic factors. In post hoc analysis of PET score, significant differences in RFS were observed between PET scores 2 and 3 as well as scores 1 and 3. No significant difference in RFS was observed between scores 1 and 2. Only PET score was statistically significant for OS in univariate analysis. None of the PET parameters were statistically significant for OS in multivariate analysis.CONCLUSION: High SUVmax and high MTV of the primary tumor suggest a high risk of recurrence for AGC patients. Even if SUVmax is similar, the prognosis may vary depending on MTV. Combining PET parameters results in a better prediction for prognosis.
Electrons ; Glycolysis ; Humans ; Multivariate Analysis ; Positron-Emission Tomography and Computed Tomography ; Prognosis ; Recurrence ; Stomach Neoplasms ; Tumor Burden

PURPOSE: Following determination of the maximum standardized uptake values (SUVmax) of the mediastinal lymph nodes (SUV-LN) and of the primary tumor (SUV-T) on ¹⁸F-FDG PET/CT in patients with non-small-cell lung cancer (NSCLC), the aim of the study was to determine the value of the SUV-LN/SUV-T ratio in lymph node staging in comparison with that of SUV-LN.METHODS: We retrospectively reviewed a total of 289 mediastinal lymph node stations from 98 patients with NSCLC who were examined preoperatively for staging and subsequently underwent pathologic studies of the mediastinal lymph nodes. We determined SUV-LN and SUV-R for each lymph node station on ¹⁸F-FDG PET/CT and then classified each station into one of three groups based on SUV-T (low, medium and high SUV-T groups). Diagnostic performance was assessed based on receiver operating characteristic (ROC) curve analysis, and the optimal cut-off values that would best discriminate metastatic from benign lymph nodes were determined for each method.RESULTS: The average of SUV-R of malignant lymph nodes was significantly higher than that of benign lymph nodes (0.79±0.45 vs. 0.36±0.23, P<0.0001). In the ROC curve analysis, the area under the curve (AUC) of SUV-R was significantly higher than that of SUV-LN in the low SUV-T group (0.885 vs. 0.810, P= 0.019). There were no significant differences between the AUCs of SUV-LN and of SUV-R in the medium and high SUV-T groups. The optimal cut-off value for SUV-R in the low SUV-T group was 0.71 (sensitivity 87.5 %, specificity 85.9 %).CONCLUSIONS: The SUV-R performed well in distinguishing between metastatic and benign lymph nodes. In particular, SUV-R was found to have a better diagnostic performance than SUV-LN in the low SUV-T group.
Area Under Curve ; Humans ; Lung Neoplasms ; Lung ; Lymph Nodes ; Methods ; Positron-Emission Tomography and Computed Tomography ; Retrospective Studies ; ROC Curve ; Sensitivity and Specificity

PURPOSE: This study aimed to investigate the prognostic value of metabolic tumor volume (MTV) and total lesion glycolysis (TLG), which are volume-based PET parameters, using 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) in patients with surgically resectable lung adenocarcinoma.METHODS: We retrospectively evaluated 149 patients with lung adenocarcinoma who underwent 18F-FDG PET/CT before surgical resection. Maximum standardized uptake value (SUVmax), MTV, and TLG of the primary tumor with threshold value of SUVmax 30, 40, and 50% were calculated, respectively. To compare the predictive performance of volume-based PET parameters, recurrence-free survival was assessed using the Kaplan-Meier method.RESULTS: The study included 70 males and 79 females with an average age of 65.8 years. The median follow-up time was 45.4 months. Recurrence was observed in 53 patients (35.6%). The mean ± SD SUVmax, MTV30%, and TLG(30%) of the entire cohort were 4.79 ± 2.94, 19.45 ± 24.85, and 56.43 ± 101.88, respectively. The cut-off values of MTV30% and TLG(30%) for recurrence were 11.07 ad 30.56, respectively. The 1-year recurrence-free survival (RFS) rate was 96.5% in low-MTV30% patients compared with 86.2% in high-MTV30% patients (p = 0.018) and 96.0% in low-TLG(30%) patients compared with 88.5% in high-TLG(30%) patients (p < 0.001). On univariate and multivariate analysis, TLG(30%) (HR, 2.828, p < 0.001; HR, 2.738, p < 0.001, respectively) was an independent prognostic factor for predicting recurrence-free survival (RFS).CONCLUSION: TLG(30%) value was observed to be a significant prognostic factor for RFS in patients with lung adenocarcinoma treated by surgical resection.
Adenocarcinoma ; Cohort Studies ; Electrons ; Female ; Fluorodeoxyglucose F18 ; Follow-Up Studies ; Glycolysis ; Humans ; Lung ; Male ; Methods ; Multivariate Analysis ; Positron-Emission Tomography and Computed Tomography ; Recurrence ; Retrospective Studies ; Tumor Burden

PURPOSE: This study aimed to investigate the prognostic value of metabolic tumor volume (MTV) and total lesion glycolysis (TLG), which are volume-based PET parameters, using 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) in patients with surgically resectable lung adenocarcinoma. METHODS: We retrospectively evaluated 149 patients with lung adenocarcinoma who underwent 18F-FDG PET/CT before surgical resection. Maximum standardized uptake value (SUVmax), MTV, and TLG of the primary tumor with threshold value of SUVmax 30, 40, and 50% were calculated, respectively. To compare the predictive performance of volume-based PET parameters, recurrence-free survival was assessed using the Kaplan-Meier method. RESULTS: The study included 70 males and 79 females with an average age of 65.8 years. The median follow-up time was 45.4 months. Recurrence was observed in 53 patients (35.6%). The mean ± SD SUVmax, MTV30%, and TLG(30%) of the entire cohort were 4.79 ± 2.94, 19.45 ± 24.85, and 56.43 ± 101.88, respectively. The cut-off values of MTV30% and TLG(30%) for recurrence were 11.07 ad 30.56, respectively. The 1-year recurrence-free survival (RFS) rate was 96.5% in low-MTV30% patients compared with 86.2% in high-MTV30% patients (p = 0.018) and 96.0% in low-TLG(30%) patients compared with 88.5% in high-TLG(30%) patients (p < 0.001). On univariate and multivariate analysis, TLG(30%) (HR, 2.828, p < 0.001; HR, 2.738, p < 0.001, respectively) was an independent prognostic factor for predicting recurrence-free survival (RFS). CONCLUSION TLG(30%) value was observed to be a significant prognostic factor for RFS in patients with lung adenocarcinoma treated by surgical resection.

PURPOSE: This study evaluated the usefulness of semiquantitative and volumetric PET parameters for predicting prognosis in patients with advanced gastric cancer (AGC). METHODS: We enrolled 213 patients who underwent ¹⁸F-fluoro-2-deoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) prior to curative surgery for AGC. Maximum standardized uptake value (SUVmax) and tumor-to-liver uptake ratio (TLR) were measured in all patients. Metabolic tumor volume (MTV) and total lesion glycolysis were measured in volume-measurable patients. For further quantification of FDG uptake, we developed PET prognostic scores by combining SUVmax and MTV (1: low SUVmax/low MTV; 2: high SUVmax/low MTV; 3: high SUVmax/high MTV). Comparison of PET parameters between recurrence and non-recurrence groups was performed. Univariate and multivariate analyses for recurrence-free survival (RFS) and overall survival (OS) were subsequently performed. RESULTS: The recurrence rate was 32.4% (69/213 patients). Mean SUVmax and mean MTV of the recurrence group were significantly higher than those of the non-recurrence group (p = 0.026 and p = 0.025). TLR showed marginal significance (p = 0.051). In multivariate analysis for RFS including all patients, SUVmax (p = 0.022), TLR (p = 0.010), and PET score (p = 0.003) were independent prognostic factors. In post hoc analysis of PET score, significant differences in RFS were observed between PET scores 2 and 3 as well as scores 1 and 3. No significant difference in RFS was observed between scores 1 and 2. Only PET score was statistically significant for OS in univariate analysis. None of the PET parameters were statistically significant for OS in multivariate analysis. CONCLUSION High SUVmax and high MTV of the primary tumor suggest a high risk of recurrence for AGC patients. Even if SUVmax is similar, the prognosis may vary depending on MTV. Combining PET parameters results in a better prediction for prognosis.