The feasibility of dedicated breast PET for the assessment of residual tumor after neoadjuvant chemotherapy.

PURPOSE: To evaluate the utility of ring-type dedicated breast positron emission tomography (dbPET) for the detection of the residual tumor after neoadjuvant chemotherapy (NAC). MATERIALS AND METHODS: This prospective study included 27 women with histologically proven breast cancer over a 37-month period. All patients underwent ring-type dbPET followed by whole-body PET-CT (WBPET) for preoperative tumor evaluation and re-staging after NAC. The maximum standardized uptake value (SUVmax) of the tumor lesion and the degree of confidence for the presence of the residual tumor were compared between pathological complete response (pCR) and non-pCR tumors. The sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) for the detection of a non-pCR tumor were compared between dbPET and WBPET. RESULTS: On dbPET, SUVmax was significantly higher in non-pCR than in pCR tumors (P = 0.030). The sensitivity for the detection of a non-pCR tumor was significantly higher with dbPET than with WBPET (84.2% vs 26.3%, P = 0.001). In the qualitative analysis, the sensitivity for the detection of a non-pCR tumor was also significantly higher with dbPET than with WBPET (57.9% vs 21.1%, P = 0.016). CONCLUSION: The dbPET can provide more sensitive detection of residual tumor after NAC than can WBPET.

[Dapagliflozin, a Sodium-Glucose Co-transporter-2 Inhibitor, Acutely Reduces Energy Expenditure in Brown Adipose Tissue via Neural Signals in Mice].

　Selective sodium glucose transporter-2 inhibitor (SGLT2i) treatment promotes urinary glucose excretion, thereby reducing blood glucose as well as body weight. However, only limited body weight reductions are achieved with SGLT2i administration. Hyperphagia is reportedly one of the causes of this limited weight loss. However, the effects of SGLT2i on systemic energy expenditure have not been fully elucidated. We investigated the acute effects of dapagliflozin, an SGLT2i, on systemic energy expenditure in mice. Eighteen hours after dapagliflozin administration, oxygen consumption and brown adipose tissue (BAT) expression of ucp1, a thermogenesis-related gene, were significantly decreased as compared with those after vehicle administration. In addition, dapagliflozin significantly suppressed norepinephrine (NE) turnover in BAT and c-fos expression in the rostral raphe pallidus nucleus (rRPa), which contains the sympathetic premotor neurons responsible for thermogenesis. These findings indicate that the dapagliflozin-mediated acute decrease in energy expenditure involves a reduction in BAT thermogenesis via decreased sympathetic nerve activity from the rRPa. Furthermore, common hepatic branch vagotomy abolished the reductions in ucp1 expression, NE contents in BAT, and c-fos expression in the rRPa. In addition, alterations in hepatic carbohydrate metabolism, such as decreases in glycogen contents and upregulation of phosphoenolpyruvate carboxykinase, occurred prior to the suppression of BAT thermogenesis, e.g., 6 h after dapagliflozin treatment. Collectively, these results suggest that SGLT2i acutely suppresses energy expenditure in BAT via regulation of an interorgan neural network consisting of the common hepatic vagal branch and sympathetic nerves.

Dapagliflozin, a Sodium-Glucose Co-Transporter 2 Inhibitor, Acutely Reduces Energy Expenditure in BAT via Neural Signals in Mice.

Selective sodium glucose cotransporter-2 inhibitor (SGLT2i) treatment promotes urinary glucose excretion, thereby reducing blood glucose as well as body weight. However, only limited body weight reductions are achieved with SGLT2i treatment. Hyperphagia is reportedly one of the causes of this limited weight loss. However, the effects of SGLT2i treatment on systemic energy expenditure have not been fully elucidated. Herein, we investigated the acute effects of dapagliflozin, a SGLT2i, on systemic energy expenditure in mice. Eighteen hours after dapagliflozin treatment oxygen consumption and brown adipose tissue (BAT) expression of ucp1, a thermogenesis-related gene, were significantly decreased as compared to those after vehicle treatment. In addition, dapagliflozin significantly suppressed norepinephrine (NE) turnover in BAT and c-fos expression in the rostral raphe pallidus nucleus (rRPa) which contains the sympathetic premotor neurons responsible for thermogenesis. These findings indicate that the dapagliflozin-mediated acute decrease in energy expenditure involves a reduction in BAT thermogenesis via decreased sympathetic nerve activity from the rRPa. Furthermore, common hepatic branch vagotomy abolished the reductions in ucp1 expression and NE contents in BAT and c-fos expression in the rRPa. In addition, alterations in hepatic carbohydrate metabolism, such as decreases in glycogen contents and upregulation of phosphoenolpyruvate carboxykinase, manifested prior to the suppression of BAT thermogenesis, e.g. 6 hours after dapagliflozin treatment. Collectively, these results suggest that SGLT2i treatment acutely suppresses energy expenditure in BAT via regulation of an inter-organ neural network consisting of the common hepatic vagal branch and sympathetic nerves.

[Therapeutic outcome and prognosis in S-1+CDDP chemotherapy for advanced gastric cancer--postoperative histopathological assessment].

UNLABELLED: The efficacy and prognosis with neoadjuvant chemotherapy(NAC)for advanced gastric cancer were assessed by histopathological examination of resected tumors. The subjects consisted of cases (< or =75 y.o.) having type 4/large type 3 (diameter> or = 8 cm) gastric cancer curable by resection based on preoperative imaging diagnostics. The NAC regimen consisted of oral S-1 at 80-120 mg/body on Days 1-21 and CDDP at 60 mg/m2 on Day 8. After two courses, gastrectomy with D2 or more extended lymph node dissection was performed. Based on histopathological effect grading of resected tumors, patients were classified into responder(grade 2 or above)or nonresponder(grade 1b or below)and analyzed for TS and OPRT gene expressions and prognosis. There were 5 responders and 6 nonresponders. High OPRT expression was mainly associated with responders. On the other hand, high TS expression with low OPRT expression was more frequently associated with nonresponders. At a median follow-up of more than 56 months (minimum follow-up, 54 months; maximum follow-up, 60 months), the 4-year overall survival was 36. 4%. Compared to nonresponders, responders showed a longer survival (p=0. 0864) and relapse-free period (p=0. 0414). CONCLUSION: These results suggest that NAC with S-1+CDDP is promising against resectable advanced gastric cancer; however, its true value will only emerge after completion of the ongoing phase III study of NAC plus surgery and postoperative chemotherapy for resectable large type 3/type 4 advanced gastric cancer (JCOG0501).

Quantitative assessment of therapeutic effects in the critically ischemic limb using (99m)Tc-diethylene-triamine-pentaacetic acid human serum albumin.

PURPOSE: To investigate the reliability and limitations of a new radioisotope method using (99m)Tc-diethylenetriamine-pentaacetic acid human serum albumin (Tc-99m-DTPA-HSA) and to evaluate the diagnostic ability of isotope infusion for assessing hemodynamic changes in the foot before and after treatment. METHODS: Hemodynamic changes before and after treatment were assessed in 21 limbs with ulcer or gangrene, by analyzing changes in the time-activity curve, the uptake ratio, and the values obtained with noninvasive techniques. RESULTS: There were significant differences between each pair of the three types of time-activity curve and their uptake counts. The uptake ratio was correlated with ankle blood pressure (ABP) and toe blood pressure (TBP), but not with transcutaneous oxygen pressure (tcPO(2)) or skin perfusion pressure (SPP). The hemodynamic change induced by pharmacotherapy was subtle, but that induced by arterial reconstruction was remarkable. Although there was not always a good correlation between the degree of hemodynamic change and the clinical outcome in limbs treated with pharmacotherapy, the hemodynamic change was quantitatively assessed. CONCLUSION: Our study suggests that this isotope technique is a useful quantitative method to evaluate hemodynamic change from a different perspective to conventional noninvasive methods.

Neuronal pathway from the liver modulates energy expenditure and systemic insulin sensitivity.

Coordinated control of energy metabolism and glucose homeostasis requires communication between organs and tissues. We identified a neuronal pathway that participates in the cross talk between the liver and adipose tissue. By studying a mouse model, we showed that adenovirus-mediated expression of peroxisome proliferator-activated receptor (PPAR)-g2 in the liver induces acute hepatic steatosis while markedly decreasing peripheral adiposity. These changes were accompanied by increased energy expenditure and improved systemic insulin sensitivity. Hepatic vagotomy and selective afferent blockage of the hepatic vagus revealed that the effects on peripheral tissues involve the afferent vagal nerve. Furthermore, an antidiabetic thiazolidinedione, a PPARg agonist, enhanced this pathway. This neuronal pathway from the liver may function to protect against metabolic perturbation induced by excessive energy storage.