Comparison of Visceral Fat Reduction by Ipragliflozin and Metformin in Elderly Type 2 Diabetes Patients: Sub-Analysis of a Randomized-Controlled Study.

INTRODUCTION: To compare the effects of ipragliflozin, a sodium-glucose transporter 2 inhibitor, with those of metformin on visceral fat (as well as muscles and bones) in Japanese elderly patients with type 2 diabetes (T2D), we conducted a sub-analysis of a prospective, multicenter, blinded-endpoint randomized-controlled study. METHODS: In total, 103 patients with T2D (body mass index ≥ 22 kg/m2; glycated hemoglobin, 7-10%) and being treated with sitagliptin (a dipeptidyl peptidase-4 inhibitor) were included and randomized to receive ipragliflozin or metformin. The primary outcome was the change in visceral fat area measured using computed tomography 24 weeks following treatment. The secondary outcomes included changes in subcutaneous and total fat area, muscle volume, bone density measured using computed tomography, handgrip strength, bone markers, plasma glucose, insulin, homeostasis model assessment (HOMA)2-beta, HOMA2-R, glycated hemoglobin, lipid panel, uric acid, blood pressure, adiponectin, and high-sensitivity C-reactive protein. All patients aged 65-74 years were selected for sub-analysis. RESULTS: The sub-analysis included 15 and 14 patients in the ipragliflozin and metformin groups, respectively. The patients' backgrounds were well balanced. Visceral fat area reduction was greater in the ipragliflozin group than in the metformin group (- 10.58% vs. - 6.93%; P = 0.034). There were significant differences in the changes in bone absorption markers, uric acid, and total cholesterol levels between the groups. CONCLUSION: Ipragliflozin significantly reduced the visceral fat area compared with metformin when added to sitagliptin in elderly patients with T2D. Long-term and large-scale studies are required to elucidate whether ipragliflozin is suitable for elderly patients. TRIAL REGISTRATION: The study was registered at https://www.umin.ac.jp/ctr/ (UMIN-ID: UMIN 000015170).

Comparing the effects of ipragliflozin versus metformin on visceral fat reduction and metabolic dysfunction in Japanese patients with type 2 diabetes treated with sitagliptin: A prospective, multicentre, open-label, blinded-endpoint, randomized controlled study (PRIME-V study).

A prospective, multicentre, open-label, blinded-endpoint, randomized controlled study was conducted to evaluate the efficacy of treatment with ipragliflozin (sodium-dependent glucose transporter-2 inhibitor) versus metformin for visceral fat reduction and glycaemic control among Japanese patients with type 2 diabetes treated with sitagliptin, HbA1c levels of 7%-10%, and body mass index (BMI) ≥ 22 kg/m2 . Patients were randomly assigned (1:1) to receive ipragliflozin 50 mg or metformin 1000-1500 mg daily. The primary outcome was change in visceral fat area as measured by computed tomography after 24 weeks of therapy. The secondary outcomes were effects on glucose metabolism and lipid metabolism. Mean percentage reduction in visceral fat area was significantly greater in the ipragliflozin group than in the metformin group (-12.06% vs. -3.65%, P = 0.040). Ipragliflozin also significantly reduced BMI, subcutaneous fat area, waist circumference, fasting insulin, and homeostatic model assessment (HOMA)-resistance, and increased HDL-cholesterol levels. Metformin significantly reduced HbA1c and LDL-cholesterol levels and increased HOMA-beta. There were no severe adverse events. The use of ipragliflozin or metformin in combination with dipeptidyl peptidase-4 inhibitors, widely used in Japan, may have beneficial effects in ameliorating multiple cardiovascular risk factors.

Efficacy and safety of ipragliflozin and metformin for visceral fat reduction in patients with type 2 diabetes receiving treatment with dipeptidyl peptidase-4 inhibitors in Japan: a study protocol for a prospective, multicentre, blinded-endpoint phase IV randomised controlled trial (PRIME-V study).

INTRODUCTION: In Japan, dipeptidyl peptidase-4 (DPP-4) inhibitors are frequently used as the treatment of choice for patients with type 2 diabetes. In some cases, however, poor glycaemic and body weight control issues persist despite treatment with DPP-4 inhibitors. Previous researchers have revealed that sodium-dependent glucose transporter-2 (SGLT-2) inhibitors reduce both plasma glucose levels and body weight in patients with type 2 diabetes. However, further investigation regarding the effects of SGLT-2 inhibitors on body composition, especially in the Asian population who tends to have relatively low-to-moderate body mass indices, is required. Therefore, we aim to determine the effects of treatment with SGLT-2 inhibitors or metformin for reducing visceral fat in 106 Asian patients with type 2 diabetes who were undergoing treatment with the DPP-4 inhibitor sitagliptin (50 mg daily) for poor glycaemic control. METHODS AND ANALYSIS: A prospective, multicentre, blinded-endpoint phase IV randomised controlled study will be conducted to evaluate the safety and efficacy of a 24-week treatment with either an SGLT-2 inhibitor (ipragliflozin) or metformin for reducing visceral fat and plasma glucose levels in patients with type 2 diabetes. Patients who satisfy the eligibility criteria will be randomised (1:1) to receive ipragliflozin (50 mg daily) or metformin (1000 mg daily). The primary outcome is the rate of change in the total area of visceral fat for patients in both treatment groups, measured using CT, after 24 weeks of therapy. Two radiologists, blinded to the clinical information, will perform centralised analysis of the images in a unified measurement condition. ETHICS AND DISSEMINATION: The protocol was approved by the institutional review board of each hospital. This study is ongoing and due to finish in April 2017. The findings of this study will be disseminated via peer-reviewed publications and conference presentations, and will also be disseminated to participants. TRIAL REGISTRATION NUMBER: UMIN000015170, R000016861 (https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000016861); Pre-results.

Prognostic relevance of apparent diffusion coefficient obtained by diffusion-weighted MRI in pancreatic cancer.

BACKGROUND: Diffusion-weighted magnetic resonance imaging (DW-MRI) is utilized as a method of oncologic imaging for predicting treatment outcomes. This study explored the role of DW-MRI in the treatment of patients with resected pancreatic cancer by comparing apparent diffusion coefficient (ADC) values with clinicopathological findings and survival rates. MATERIALS AND METHODS: Records of 54 patients in whom DW-MRI at 1.5T was performed (b values: 0 and 1000 mm(2) /s) before macroscopically curative resection were analyzed. ADC values were then calculated and compared with clinicopathological factors including age, gender, serum carcinoembryonic antigen levels, serum carbohydrate antigen 19-9 levels, lymph node metastasis, primary tumoral location, size, differentiation, resectability, and pT stage. A survival analysis of clinicopathological factors and ADC values was performed using the Kaplan-Meier method, and the results were evaluated with the log-rank test. Prognostic significance was assessed using the Cox proportional hazard model. RESULTS: Significant associations were found between tumor differentiation and ADC values (P = 0.001). In a univariate analysis of overall survival, tumor differentiation (P = 0.037) and ADC values (P = 0.002) were identified as significant prognostic factors. However, age, gender, carcinoembryonic antigen levels, carbohydrate antigen 19-9 levels, lymph node metastasis, primary tumoral location, size, resectability, and pT stage were not associated with overall survival. In a multivariate analysis of overall survival, only ADC values were identified as significant prognostic factors (hazard ratio 2.293, 95% confidence interval 1.147-4.585, P = 0.019). CONCLUSION: ADC values were found to be associated with prognosis in patients with resected pancreatic cancer.

Massive gas embolism revealed by two consecutive postmortem computed-tomography examinations.

We present a case of unusual gas embolism in a 73-year-old man who was found in a state of cardiopulmonary arrest with an oxygen-supply tube connected to an intravenous catheter inserted into his median cubital vein. Postmortem computed tomography (PMCT) performed 27 h after death showed systemic gas distribution including intravascular gas, pneumothorax, pneumoperitoneum, pneumomediastinum, pneumoretroperitoneum and gastric emphysema. A second PMCT scan performed 116 h after death showed a marked decrease of air inside the body. The current case shows the importance of PMCT for visualization, quantification, and preservation of evidence for establishment of the cause of death in cases with suspected gas embolism. Our findings also indicate that performance of two PMCT examinations may be useful for differentiation of embolized gas from gas produced by putrefaction.

Gadoxetic acid-enhanced MRI compared with CT during angiography in the diagnosis of hepatocellular carcinoma.

PURPOSE: To assess the value of gadoxetic acid-enhanced magnetic resonance imaging (MRI) for the pre-therapeutic detection of hepatocellular carcinoma (HCC) using receiver operating characteristic (ROC) analysis with the combination of computed tomography (CT) arterial portography and CT hepatic arteriography (CTAP/CTHA). MATERIALS AND METHODS: A total of 54 consecutive patients with 87 nodular HCCs were retrospectively analyzed. All HCC nodules were confirmed pathologically. Three blinded readers independently reviewed 432 hepatic segments, including 78 segments with 87 HCCs. Each reader read two sets of images: Set 1, CTAP/CTHA; Set 2, gadoxetic acid-enhanced MRI including a gradient dual-echo sequence and diffusion-weighted imaging (DWI). The ROC method was used to analyze the results. The sensitivity, specificity, positive predictive value, negative predictive value and sensitivity according to tumor size were evaluated. RESULTS: For each reader, the area under the curve was significantly higher for Set 2 than for Set 1. The mean area under the curve was also significantly greater for Set 2 than for Set 1 (area under the curve, 0.98 vs. 0.93; P=.0009). The sensitivity was significantly higher for Set 2 than for Set 1 for all three readers (P=.012, .013 and .039, respectively). The difference in the specificity, positive predictive values and negative predictive values of the two modalities for each reader was not significant (P>.05). CONCLUSION: Gadoxetic acid-enhanced MRI including a gradient dual-echo sequence and DWI is recommended for the pre-therapeutic evaluation of patients with HCC.

A pictorial review of benign hepatocellular nodular lesions: comprehensive radiological assessment incorporating the concept of anomalous portal tract syndrome.

BACKGROUND/PURPOSE: Although the pathological categorization system advocated by the International Working Party (IWP) on Terminology has been helpful in categorizing benign hepatocellular lesions, the diverse clinicopathological features of the lesions still cause confusion of diagnosis in clinical settings. Recently, an integrated disease concept termed "anomalous portal tract syndrome" (APTS) has been proposed as a congenital anomaly of the portal tract, being a single unifying etiological factor underlying the disorder. In this article, we discuss the radiological features of benign nodular hepatocellular lesions incorporated in the concept of APTS. METHODS: We systematically reviewed the literature on benign hepatocellular lesions based on the concept of APTS, as well as standard IWP terminology. For this pictorial review, we selected six representative cases and assessed the radiological features of the cases based on the concept of APTS. RESULTS: The comprehensive assessment based on APTS enabled the systematic categorization of benign hepatocellular lesions, including nodular regenerative hyperplasia, large regenerative nodules, partial nodular transformation, focal nodular hyperplasia, and hepatocellular adenoma, and was helpful in understanding the overlapping features of these lesions. CONCLUSIONS: Although the disease concept of APTS is still evolving, it is nonetheless helpful in comprehensively understanding the clinicopathological and radiological features of various benign hepatocellular lesions.

Application of postmortem 3D-CT facial reconstruction for personal identification.

Postmortem computed tomography (CT) images can show internal findings related to the cause of death, and it can be a useful method for forensic diagnosis. In this study, we scanned a ready-made box by helical CT on 2-mm slices in a mobile CT scanner and measured each side of the box to assess whether reconstructed images are useful for superimposition. The mean difference between the actual measurements and the measurements on the three-dimensional (3D) reconstructed images (3D-CT images) is 0.9 mm; we regarded it as having no effect on reconstruction for the superimposition method. Furthermore, we could get 3D-CT images of the skull, which were consistent with the actual skull, indicating that CT images can be applied to superimposition for identification. This study suggested that postmortem CT images can be applied as superimpositions for unidentified cases, and thinner slices or cone beam CT can be a more precise tool.

Magnetic resonance imaging of hepatocellular carcinoma: a pictorial review of novel insights into pathophysiological features revealed by magnetic resonance imaging.

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Magnetic resonance (MR) imaging is one of the most powerful modalities for the assessment of HCC with sufficient sensitivity and specificity. In addition to its capacity for lesion detection, MR imaging delineates some unique in vivo pathophysiological features of tumors, which cannot be assessed by other modalities. Chemical shift imaging may depict steatosis of the tumor. Dynamic contrast-enhanced MR imaging is the most powerful tool to assess the vascularity of the tumor, which is closely related to malignant transformation in hepatocarcinogenesis. Diffusion-weighted imaging illustrates the cellularity of the tumor. Super-paramagnetic iron oxide, a liver-specific MR contrast agent accumulating in Kupffer cells, enables detection of the hepatocellular architecture in the lesion. Recently, a new liver-specific MR contrast agent, gadoxetic acid [gadolinium-ethoxybenzyl (Gd-EOB)-diethylenetriaminopentoacetic acid (DTPA)], has been introduced for clinical imaging. Gd-EOB-DTPA has a significant impact on the imaging of HCC, with potential capacity for the concurrent assessment of vascularity of the tumor and hepatocellular-specific properties within the tumor. Understanding the characteristics of MR imaging methods and contrast agents is essential for the optimal diagnosis and characterization of HCCs.

Applicability of facial soft tissue thickness measurements in 3-dimensionally reconstructed multidetector-row CT images for forensic anthropological examination.

PURPOSE: The purpose of this study is to assess the applicability of facial soft tissue measurements using 3-dimensional reconstructed MDCT and to compare the results with previously reported Japanese data. METHODS AND MATERIALS: This study included 50 Japanese cadavers who underwent postmortem whole body 16-detector CT within 0-3 days after death. Using 3-D workstation, 10 anthropological measuring points were located and the soft tissue thicknesses were measured. The differences between the acquired thickness and the previously reported Japanese average thickness were statistically analyzed. RESULTS: All measuring points were readily determined on the 3-dimensional reconstructed images. Previous Japanese cadaveric data was thinner than our data in almost all sites except for 1 measuring point (mid-philtrum). Previous living Japanese data was thicker than ours except for 1 measuring point (end of nasal). CONCLUSION: Facial soft tissue thickness was easily assessed using 3-D reconstructed MDCT images. At many measuring points, our results were thicker than previously reported cadaveric data and were thinner than the data from live persons.

What is the origin of intravascular gas on postmortem computed tomography?

PURPOSE: Intravascular gas is frequently demonstrated on postmortem computed tomography (PMCT). The purpose of this study is to classify the distribution patterns of intravascular gas and to determine its developmental mechanism. METHOD AND MATERIALS: The series included 43 cases (mean age, 62 years). All causes of death were non-traumatic (14 cases, sudden death; 29 cases, death caused by known disease). Using a 16-row multi-detector CT, whole body images were obtained with 1.25-mm collimation. Gas in veins, right heart was classified as venous gas. Gas in arteries, left heart was classified as arterial gas. RESULTS: PMCT showed intravascular gas in 20 cases. Distribution of gas was divided into 2 patterns; pattern 1 (11 cases): a small volume of venous gas (superior and inferior vena cava, right heart, subclavian veins and brachiocephalic veins) and no arterial gas; pattern 2 (9 cases): both venous (same positions of pattern 1 plus hepatic veins) and arterial gas (left heart, ascending aorta, vertebral arteries and cerebral arteries). CONCLUSION: Since imaging findings of pattern 1 are similar to those frequently demonstrated after intravenous contrast-enhanced CT, this gas is presumed to be of exogenous origin from intravenous catheters. In contrast, the gas in pattern 2 may be of endogenous origin, such as decompression disease. Bubbles should move through the ventral side of vessels in the supine position, and subsequently must be trapped by extruded anatomical structures to the ventral side, for example, right ventricle, vertebral and cerebral arteries, hepatic veins and renal veins.

Sarcoidosis presenting as prepatellar bursitis.

A 61-year-old woman complained of a subcutaneous mass in her right knee. MR images revealed a well-defined subcutaneous mass in the prepatellar region, containing some fluid and foci of short T2. The lesion showed some marginal contrast uptake after an administration of meglumine gadopentetate (Gd-DTPA), consistent with prepatellar bursitis. The pathological specimen, however, revealed subcutaneous sarcoidosis involving the bursa.

Diffusion-weighted imaging of prostate cancer.

OBJECTIVE: The purpose of this study was to assess whether T2-weighted (T2W) imaging with diffusion-weighted (DW) imaging could improve prostate cancer detection as compared with T2W imaging alone. METHODS: The subjects consisted of 37 patients with prostate cancer and 23 without cancer undergoing magnetic resonance (MR) imaging. Using a 1.5-T superconducting magnet, all patients underwent T2W and DW imaging with parallel imaging. Images were independently reviewed by 3 readers to determine the detectability of prostate cancer. The detectability of T2W imaging without and with DW imaging was assessed by means of receiver operating characteristic analysis. RESULTS: Mean areas under the receiver operating characteristic curve for T2W imaging alone and for T2W imaging with DW imaging were 0.87 and 0.93, respectively. The receiver operating characteristic analysis showed that the addition of DW imaging to conventional T2W imaging significantly improved tumor detection (P = 0.0468) compared with T2W imaging alone. CONCLUSIONS: The addition of DW imaging to conventional T2W imaging provides better detection of prostate cancer.