Effects of Lenvatinib on Skeletal Muscle Volume and Cardiac Function in Patients with Hepatocellular Carcinoma.

INTRODUCTION: Previously, we reported that the tyrosine kinase inhibitor (TKI) sorafenib decreases serum levels of carnitine and reduces skeletal muscle volume. Moreover, others reported that TKIs might lead to cardiomyopathy or heart failure. Therefore, this study aimed to evaluate the effects of lenvatinib (LEN) on skeletal muscle volume and cardiac function in patients with hepatocellular carcinoma (HCC). METHODS: This retrospective study included 58 adult Japanese patients with chronic liver diseases and HCC treated with LEN. Blood samples were collected before and after 4 weeks of treatment, and serum carnitine fraction and myostatin levels were measured. Before and after 4-6 weeks of treatment, the skeletal muscle index (SMI) was evaluated from computed tomography images and cardiac function was assessed by ultrasound cardiography. RESULTS: After treatment, SMI, serum levels of total carnitine, and global longitudinal strain were significantly lower, but serum levels of myostatin were significantly higher. Left ventricular ejection fraction showed no significant change. CONCLUSION: In patients with HCC, LEN decreases serum levels of carnitine, skeletal muscle volume, and worsens cardiac function.

Lenvatinib Might Induce Activation of Host Immunity in Patients with Hepatocellular Carcinoma.

INTRODUCTION: Atezolizumab, an immune checkpoint inhibitor, plus bevacizumab, a monoclonal antibody that binds to vascular endothelial growth factor (VEGF), is an approved first-line systemic treatment for unresectable hepatocellular carcinoma (HCC). Immune checkpoint inhibitors are more effective in patients with HCC when administered with anti-VEGF drugs; however, these drugs affect host immunity. Lenvatinib is an anti-VEGF agent used to treat HCC; therefore, this study evaluated the effect of treatment of HCC with lenvatinib on host immunity in patients with chronic liver disease (CLD). METHODS: We studied adult Japanese patients with CLD and unresectable HCC treated with lenvatinib at our hospital. Lenvatinib was administered for 4 weeks (8 mg/day for bodyweight <60 kg; 12 mg/day for bodyweight >60 kg). Blood samples were collected at baseline and at 4 weeks of treatment and examined for immune-related changes. RESULTS: Forty-three patients were enrolled in this study. We found a significant increase in T helper (Th) 1 cells following 4 weeks of lenvatinib treatment, although there was no significant difference in Th2 cells and regulatory T cells. We also found a significant increase in serum levels of TNF-alpha, soluble TNF-alpha receptor I, and endothelial growth factor following 4 weeks of lenvatinib treatment. Furthermore, an increase in Th1 cells and serum levels of TNF-alpha was found in patients with partial response. CONCLUSION: Lenvatinib might induce Th1-dominant host immunity in patients with CLD and unresectable HCC treatment in patients who showed a partial response. These changes in host immunity may be a biomarker in HCC patients treated with lenvatinib.

Tivantinib Decreases Hepatocyte Growth Factor-Induced BCRP Expression in Hepatocellular Carcinoma HepG2 Cells.

Tivantinib, a mesenchymal-epithelial transition factor (cMET) inhibitor, is a molecular targeting drug that kills hepatocellular carcinoma (HCC) cells. Tivantinib alone does not affect the overall survival of patients with HCC, and combination treatment with tivantinib and other therapies has not been evaluated. This study was conducted to clarify the effect of the tivantinib in regulating breast cancer therapy-resistant protein (BCRP), a key transporter of 5-fluorouracil (5-FU), and dihydropyridine dehydrogenase (DPYD), a major metabolic enzyme of 5-FU. To this end, cMET gene expression was determined by RT-PCR in HepG2 (human hepatoma) cells. The transcriptional start sites of BCRP were determined by 5'-rapid amplification of cDNA ends (5'-RACE). BCRP and DPYD mRNA levels were determined by real-time RT-PCR, and promoter activities were measured by dual-luciferase assays. Results show that hepatocyte growth factor (HGF) upregulated the mRNA level of BCRP, but not DPYD, in HepG2 cells. The upregulation of BCRP expression by HGF was down-regulated by tivantinib. We also identified two transcriptional start sites (E1α, E1ß) in BCRP by 5'-RACE. The transcriptional activity of the region -287 to E1α of BCRP was upregulated by HGF, which was decreased by tivantinib, whereas activity of the region -297 to E1ßo f BCRP was not affected by tivantinib. Therefore, tivantinib regulates BCRP expression upstream of exon 1α. Combination treatment of tivantinib and 5-FU should be further evaluated for HCC therapy.

[Coronary Computed Tomography Angiography for Patients with Atrial Fibrillation: Feasibility of Prospective Electrocardiography-gated Diastolic Acquisition with a Manual Exposure-termination Technique].

Coronary computed tomography angiography (CCTA) was performed in 283 patients with atrial fibrillation (Af) using a prospective electocardiogeaphic gated scanning with a manual exposure-termination technique. When preparatory 5-beat scanning contained at least one RR interval longer than 800 ms, 5-beat diastolic scanning (R+800 ms protocol) was selected. When no RR interval longer than 800 ms was observed, 2-beat scanning starting at end-systolic phase (R+210 ms to R protocol) was chosen. In R+800 ms protocol, we manually terminated scanning when motion free real-time reconstruction image was confirmed. R+800 ms protocol was applied in 95% of the cases and required an average of 2 cardiac cycles, providing motion-free images in 91% of the patients. The mean exposure dose was less than that with R+210 ms to R protocol. Using the protocols above, 90% of the all patients with Af provided motion free images and 99% of them were evaluable.

Pacemaker-induced Metallic Artifacts in Coronary Computed Tomography Angiography: Clinical Feasibility of Single Energy Metal Artifact Reduction Technique.

BACKGROUND: Coronary computed tomography angiography (CCTA) in patients with pacemaker suffers from metallic lead-induced artifacts, which often interfere with accurate assessment of coronary luminal stenosis. The purpose of this study was to assess a frequency of the lead-induced artifacts and artifact-suppression effect by the single energy metal artifact reduction (SEMAR) technique. METHODS: Forty-one patients with a dual-chamber pacemaker were evaluated using a 320 multi-detector row CT (MDCT). Among them, 22 patients with motion-free full data reconstruction images were the final candidates. Images with and without the SMEAR technique were subjectively compared, and the degree of metallic artifacts was compared. RESULTS: On images without SEMAR, severe metallic artifacts were often observed in the right coronary artery (#1, #2, #3) and distal anterior descending branch (#8). These artifacts were effectively suppressed by SEMAR, and the luminal accessibility was significantly improved in #3 and #8. CONCLUSION: While pacemaker leads often cause metallic-induced artifacts, SEMAR technique reduced the artifacts and significantly improved the accessibility of coronary lumen in #3 and #8.

[The Minimum Values of (RR-PQ) for High Quality Coronary CT Angiogram in Half, Automatic Patient's Motion Correction (APMC) and Full Reconstruction Using 320-ADCT (0.275 s/r)].

BACKGROUND: A clear coronary CT angiography (CCTA) can be obtained when temporal resolution (TR) is shorter than slow filling (SF) duration. The SF duration was calculated by the following equation: SF=-443+0.742 (RR-PQ). Although, the TR of half and full reconstruction using 320-ADCT (0.275 s/r) are known, the TR of automatic patient motion correction (APMC) reconstruction is not clear. The purpose of this study is to clarify the each minimum value of (RR-PQ) for acquiring a clear CCTA that was made by half, full or APMC reconstruction. METHOD: CCTA was performed in consecutive 345 (M/F=195/150, Age: 69±10 years) patients except for arrhythmia and the final heart rate (controlled by ß-blocker) ≥80 bpm using 320-ADCT (Aquilion ONE, 0.275 s/r). In all subjects, 3 CCTAs were generated by half, full, or APMC reconstruction at the same optimal phase. Image quality (A: excellent, B: acceptable, C: poor) was estimated by the consensus of three trained researchers. We classified (RR-PQ) into 15 groups by each 50 ms interval. RESULTS: The A or B % prediction (y) significantly correlated (y=-240.08+0.401x, r=0.98, p=0.0006 in half, y=-238.26+0.378x, r=0.98, p=0.0001 in APMC, and y=-236.84+0.332x, r=0.97, p<0.0001 in full reconstruction) with (RR-PQ) (x), respectively. CONCLUSION: The minimum values of (RR-PQ) for 95% prediction of A or B image quality were ≥836 ms in half, ≥881 ms in APMC, and ≥998 ms in full reconstruction.

[Clinical usefulness of low tube current scanning with full reconstruction and automatic patient motion correction (APMC) reconstruction in a prospective ECG-gated coronary CT angiography using 320-row area detector CT].

PURPOSE: The purpose of this study is to validate the clinical usefulness of Advanced Patient Motion Correction (APMC) reconstruction when motion artifacts were observed in a prospective ECG-gated coronary CT angiography (CCTA), which was acquired by low tube current scanning with full reconstruction using 320-row area detector CT (0.275 s/rot.). METHODS: Of 530 consecutive CCTA, we selected 119 patients (M/F: 71/48, Age: 69 ± 11 y, BMI: 23.5 ± 2.5) with (RR-PQ) ≥ 968 ms before scanning, and performed a CCTA with low tube current scanning [30% of usual tube current (30%mA)], adaptive iterative dose reduction 3D, and full reconstruction. Image quality for motion artifacts was subjectively evaluated using a 3-point scale (excellent, acceptable, and unacceptable). RESULTS: Of 119, 102 CCTA had "excellent" images (group A) and 17 had "acceptable" images (group B). The APMC and half reconstruction were retried in the 17 CCTA with "acceptable" images. Finally, all CCTA became "excellent" images. The RR-PQ of group B during scanning (966 ± 80 ms) was significantly (P = 0.0001) shorter than group A (1,088 ± 123 ms). Each image noise (standard deviation of CT value) of aorta, left atrium, and left ventricle was 21.7 ± 2.3, 24.7 ± 2.3, 24.5 ± 2.4 in full, 25.7 ± 2.2, 29.0 ± 3.4, 28.2 ± 2.7 in APMC, and 30.4 ± 2.8, 34.3 ± 4.2, 33.3 ± 2.9 HU in half reconstruction. Mean dose-length product of all patients was 66.2 ± 34.4 mGy · cm. CONCLUSION: "Excellent" CCTA images can be obtained in 85.7% of patients with (RR-PQ)≥ 968 ms by full reconstruction. APMC is useful for motion artifacts and image noise reduction when patient' s HR increases during scanning rather than half reconstruction.

Using Dictionary Matching to Improve the Accuracy of MOLLI Myocardial T1 Analysis and Measurements of Heart Rate Variability.

We analyzed modified Look-Locker inversion recovery (MOLLI) T1 measurements by applying a dictionary matching strategy and aimed to acquire T1 measurements more accurately than those acquired by the conventional three-parameter matching analysis. We particularly clarified the robustness of this method for measuring heart rate (HR) variability. A phantom experiment using a 3T MRI system was performed for various HRs. The ideal MOLLI signal corresponding to the scan parameter in the MRI experiment was simulated over a wide range of T1 values according to the dictionary. The unknown T1 values were determined by finding the simulated signals in the dictionary corresponding to the measured signals using pattern matching. The measured T1 values showed that the proposed analysis improved the accuracy of T1 measurements compared to those acquired by traditional analysis by up to 10%. In addition, the variability of measurements at several HRs was reduced by up to 100 ms.

Novel T1 Analysis Method to Address Reduced Measurement Accuracy Due to Irregular Heart Rate Variability in Myocardial T1 Mapping Using Polarity-corrected Inversion Time Preparation.

PURPOSE: Polarity-corrected inversion time preparation (PCTIP), a myocardial T1 mapping technique, is expected to reduce measurement underestimation in the modified Look-Locker inversion recover method. However, measurement precision is reduced, especially for heart rate variability. We devised an analysis using a recurrence formula to overcome this problem and showed that it improved the measurement accuracy, especially at high heart rates. Therefore, this study aimed to determine the effect of this analysis on the accuracy and precision of T1 measurements for irregular heart rate variability. METHODS: A PCTIP scan using a 3T MRI scanner was performed in phantom experiment. We generated the simulated R-waves required for electrocardiogram (ECG)-gated acquisition using a signal generator set to 30 combinations. T1 map was generated using the signal train of the PCTIP images by nonlinear curve fitting using conventional and recurrence formulas. Accuracy against reference T1 and precision of heart rate variability were evaluated. To evaluate the fitting accuracy of both analyses, the relative fitting error was calculated. RESULTS: For the longer T1, the fitting error was larger than the short T1, with the conventional analysis showing 10.1±2.0%. The recurrence formula analysis showed a small fitting error less than 1%, which was consistent for all heart rate variability patterns. In the conventional analysis, the accuracy, especially for longer T1, showed a large underestimation of the measurements and poor linearity. However, in the recurrence formula analysis, the accuracy improved at a long T1, and linearity also improved. The Bland-Altman plot showed that it varied greatly depending on the heart rate variability pattern for the longer T1 in the conventional analysis, whereas the recurrence formula analysis suppressed this variation. CONCLUSION: T1 analysis of PCTIP using the recurrence formula analysis achieved accurate and precise T1 measurements, even for irregular heart rate variability.

Associations among parenting experiences during childhood and adolescence, hypothalamus-pituitary-adrenal axis hypoactivity, and hippocampal gray matter volume reduction in young adults.

Recent human studies have indicated that adverse parenting experiences during childhood and adolescence are associated with adulthood hypothalamus-pituitary-adrenal (HPA) axis hypoactivity. Chronic HPA axis hypoactivity inhibits hippocampal gray matter (GM) development, as shown by animal studies. However, associations among adverse parenting experiences during childhood and adolescence, HPA axis activity, and brain development, particularly hippocampal development, are insufficiently investigated in humans. In this voxel-based structural magnetic resonance imaging study, using a cross-sectional design, we examined the associations among the scores of parental bonding instrument (PBI; a self-report scale to rate the attitudes of parents during the first 16 years), cortisol response determined by the dexamethasone/corticotropin-releasing hormone test, and regional or total hippocampal GM volume in forty healthy young adults with the following features: aged between 18 and 35 years, no cortisol hypersecretion in response to the dexamethasone test, no history of traumatic events, or no past or current conditions of significant medical illness or neuropsychiatric disorders. As a result, parental overprotection scores significantly negatively correlated with cortisol response. Additionally, a significant positive association was found between cortisol response and total or regional hippocampal GM volume. No significant association was observed between PBI scores and total or regional hippocampal GM volume. In conclusion, statistical associations were found between parental overprotection during childhood and adolescence and adulthood HPA axis hypoactivity, and between HPA axis hypoactivity and hippocampal GM volume reduction in healthy young adults, but no significant relationship was observed between any PBI scores and adulthood hippocampal GM volume.

Usefulness of partial splenic embolization for left-sided portal hypertension in a patient with a pancreatic neuroendocrine neoplasm: a case report and review of the literature.

Left-side portal hypertension (LSPH) is caused by isolated obstruction of the splenic vein and is associated with esophagogastric varices that extend from the lower esophagus to the greater curvature of the gastric body. Here, we report on a 74-year-old man with a pancreatic neuroendocrine neoplasm (NEN) in the pancreatic tail with multiple liver metastases. We decided that partial splenic embolization (PSE) was the best course of treatment to prevent rupture of the gastric varices, which were classified as markedly enlarged, nodular, or tumor-shaped and showed erosion of the mucosa. After PSE, the patient had no major complications and was discharged. At 3 and 6 months after the procedure, esophagogastroduodenoscopy and enhanced computerized tomography showed that the gastric varices had improved. This case demonstrates the usefulness of PSE for LSPH in patients with unresected pancreatic NEN.

Adaptation of lenvatinib treatment in patients with hepatocellular carcinoma and portal vein tumor thrombosis.

PURPOSE: The aim of this study was to clarify the adaptation of lenvatinib treatment in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT). METHOD: Fifty-three patients with HCC were treated with lenvatinib. Before and after treatment blood sampling, patients were examined by computed tomography and ultrasonography. In patients with portal trunk invasion (Vp4), the analysis focused on the degree of occlusion due to the tumor in the portal trunk. In patients without major PVTT {ie, invasion of the primary branch of the portal vein [Vp3] or Vp4}, portal blood flow volume was measured by Doppler analysis; however, Doppler analysis is difficult to perform in patients with major PVTT, so the time from administration of the contrast agent to when it reached the primary branch of the portal vein (portal vein arrival time) was evaluated with the contrast agent Sonazoid. RESULTS: Patients with Vp4 had a significantly worse prognosis than patients with Vp3 and a significant increase in Child-Pugh score at 2 months. Patients with major PVTT had a poor prognosis if the degree of occlusion of the portal trunk was 70% or more. In patients without major PVTT, portal blood flow was significantly decreased after administration of lenvatinib; and in patients with major PVTT, the hepatic artery and portal vein arrival times were significantly increased. CONCLUSION: Lenvatinib treatment should be avoided in patients with Vp4 with a high degree of portal trunk occlusion because of concerns about decreased portal blood flow.

Measurement of skeletal muscle volume is useful for predicting prognosis in patients with liver cirrhosis.

BACKGROUND: Hepatic venous pressure gradient (HVPG) and the model for end-stage liver disease (MELD) score were previously reported as prognostic factors for outcome in patients with liver cirrhosis (LC), and recently, the presence of sarcopenia was reported to be an indicator of worse prognosis in these patients. AIM: This retrospective study aimed to clarify the importance of sarcopenia as a prognostic factor in patients with LC. MATERIAL AND METHODS: The MELD-Na score, HVPG, and skeletal muscle index (SMI) were measured in 202 patients between January 2013 and August 2020. We performed linear regression analysis between HVPG and SMI and calculated suitable cutoff values of HVPG for predicting presarcopenia and of HVPG, ΔSMI (i.e. the decrease in SMI per year, for predicting survival). Overall survival rates with the HVPG and ΔSMI cutoff values were compared by Kaplan-Meier estimates and log-rank tests. Prognostic factors for survival were analyzed by Cox regression univariate and multivariate analyses. RESULTS: In total, 71% (143/202) of patients presented with presarcopenia. Linear regression showed a significantly negative correlation between HVPG and SMI. Survival was significantly worse in the group with presarcopenia than in the group without. Survival was worse also in the group with an HVPG value ≥ 15 and ΔSMI ≥ -2.4. Cox regression multivariate analyses showed that MELD-Na score, HVPG, HVPG ≥ 15, ΔSMI, and ΔSMI ≥ -2.4 were independent prognostic factors. CONCLUSION: Skeletal muscle volume, especially ΔSMI, has a prognostic value equivalent to that of the MELD-Na score and HVPG.

Successful treatment of advanced pancreatic leiomyosarcoma treated with gemcitabine plus nab-paclitaxel: a case report and literature review.

Pancreatic leiomyosarcoma (PLMS) is an extremely rare tumor that accounts for 0.1% of pancreatic malignancies, and its chemotherapy has yet to be established. Generally, soft-tissue sarcoma chemotherapy is standard treatment with doxorubicin (DXR) alone. However, the effectiveness of gemcitabine (GEM) plus docetaxel (DOC) has been shown in uterine leiomyoma. In contrast, the GEM plus nab-paclitaxel (PTX) regimen has been established as first-line chemotherapy for unresectable pancreatic cancer. For this study, we selected the GEM plus nab-PTX regimen for patients with PLMS, achieving success in approximately 10 months. From a search on PubMed, we found only 12 cases of PLMS (including this case) that underwent chemotherapy. Our case is the first reported patient to have survived more than 2 years with chemotherapy alone. In a nude mouse model, the GEM plus DOC regimen was shown to significantly decrease tumor size when compared with DXR in leiomyosarcoma, and the GEM plus nab-PTX regimen was reported to significantly reduce necrosis when compared with DXR alone, GEM alone, DOC alone, nab-PTX alone and GEM plus DOC in soft-tissue sarcoma. GEM plus nab-PTX therapy might therefore be the first choice for soft-tissue sarcoma and leiomyosarcoma. This is the first reported case of PLMS treated with GEM plus nab-PTX.

Usefulness of virtual touch tissue quantification for predicting the presence of esophageal varices in patients with liver cirrhosis.

BACKGROUND AND AIM: Measuring the hepatic venous pressure gradient (HVPG) is an established technique to detect increased portal pressure and predict the presence of esophageal varices (EVs); however, the risk of the test is greater than the information it provides. This study aimed to clarify the usefulness of virtual touch tissue quantification (VTQ), which assesses liver stiffness, in predicting the presence of EVs in patients with liver cirrhosis by comparing it with HVPG. METHODS: Two hundred seventeen patients with liver cirrhosis underwent VTQ, HVPG measurement, and upper endoscopy. Patients were divided into three groups: group V, hepatitis C virus liver cirrhosis (n = 40); group A, alcoholic liver cirrhosis (n = 116); and group N, other liver cirrhosis (n = 61). In each group, we performed linear regression analysis of VTQ and HVPG data. The accuracy of VTQ and HVPG measurement in predicting the presence of EVs and high-risk EVs (EV category F2 and F3) was assessed by area under the receiver operating characteristic curve (AUROC). RESULTS: VTQ was significantly correlated with the HVPG in the whole patients and in each group, and both VTQ and HVPG values were significantly higher in patients with EVs and high-risk EVs than in those without. The AUROC for the presence of EVs for VTQ was 0.76 in the whole sample, 0.76 in group V, 0.79 in group A, and 0.67 in group N; and for HVPG, 0.92, 0.94, 0.93, and 0.88, respectively. For VTQ, the AUROC for the presence of high-risk EVs was 0.78 in the whole sample, 0.78 in group V, 0.73 in group A, and 0.73 in group N; and for HVPG, it was 0.85, 0.82, 0.85, and 0.82, respectively. CONCLUSION: VTQ was reliable at predicting the presence of EVs and high-risk EVs. Therefore, we propose that VTQ is a useful, noninvasive tool for predicting the presence of EVs in daily medical care.

Added value of contrast-enhanced CISS imaging in relation to conventional MR images for the evaluation of intracavernous cranial nerve lesions.

INTRODUCTION: The normal cranial nerves (CNs) of the cavernous sinus can be clearly demonstrated using contrast-enhanced constructive interference in steady-state (CISS) magnetic resonance imaging (MRI). This study used the method to evaluate pathological CNs III, IV, V(1), V(2), and VI in cavernous sinuses affected by inflammatory and neoplastic diseases. METHODS: MR images from 17 patients with diseases involving the cavernous sinuses and/or causing neuropathy in CNs III-VI were retrospectively evaluated. The patients were divided into inflammatory (n=11) and neoplastic (n=6) groups. We defined CNs as abnormal when they exhibited enlargement or enhancement. CNs were evaluated using both contrast-enhanced CISS and T1-weighted MRI. RESULTS: In the inflammatory group, abnormal CNs were identified by contrast-enhanced CISS MRI in 13 of 25 symptomatic CNs (52%) in eight patients, but in only two CNs (8%) in two patients by contrast-enhanced T1-weighted MRI. In the neoplastic group, both sequences of contrast-enhanced CISS and T1-weighted MRI detected abnormalities in the same three of eight symptomatic CNs (37.5%), i.e., the three CNs were all in the same patient with adenoid cystic carcinoma. CONCLUSION: Contrast-enhanced CISS MRI is useful for detecting CN abnormalities in inflammatory pathological conditions of the cavernous sinuses.

Sorafenib Might Induce Sarcopenia in Patients With Hepatocellular Carcinoma by Inhibiting Carnitine Absorption.

BACKGROUND/AIM: Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of cancers. Sorafenib, an oral multi-target TKI, improves the median overall survival time in patients with hepatocellular carcinoma (HCC). It also inhibits the absorption of carnitine by down-regulating the human organic cationic transporter OCTN2 located largely in the small intestinal mucosa and skeletal muscle. The aim of the study was to determine, by assessing carnitine metabolism, whether sarcopenia is induced in patients with HCC who are receiving sorafenib. PATIENTS AND METHODS: This retrospective study included 110 adult Japanese patients with liver cirrhosis and HCC who received sorafenib. Sorafenib was administered at a dose of 200-800 mg/day for 4 weeks. Blood samples were collected before and after treatment, and serum carnitine fraction and myostatin levels were measured. Cross-sectional areas (cm2) of the skeletal muscles at the third lumbar vertebra level were determined by manually outlining computed tomography images before and after treatment. The cross-sectional areas were normalized for height [skeletal muscle index (SMI), cm2/m2]. RESULTS: Patients were allocated to two groups according to Child-Pugh (CP) class; 81 had CP-A liver function, and 29 had CP-B. SMI after treatment was significantly lower than that before treatment in both groups. Serum levels of total carnitine and free carnitine after treatment were significantly lower than those before treatment in both groups. There were no differences in serum levels of myostatin before and after treatment in either group. CONCLUSION: Sorafenib might decrease serum levels of carnitine by inhibiting carnitine absorption. Decreasing of serum levels of carnitine might lead to presarcopenia.

An increase in the deoxygenated hemoglobin concentration induced by a working memory task during the refractory period in the hemodynamic response in the human cerebral cortex.

In activated brain regions, the deoxygenated hemoglobin (deoxy-Hb) concentration decreases despite an increase in oxygen consumption. This is attributed to the fact that the cerebral blood flow (CBF) induced by neuronal activation exceeds the accompanying increase in the cerebral metabolic rate of oxygen (CMRO2). The discrepancy between large CBF and disproportionately small CMRO2 responses provides the basis for detecting the hemodynamic correlates of neuronal activities by functional magnetic resonance imaging (fMRI). However, this implies that if the supply of oxygen is made smaller than the oxygen consumed by the suppression of stimulus-induced CBF, the polarity of signals would be reversed. We used near-infrared spectroscopy (NIRS) to search for a condition wherein a marked decrease in the stimulus-evoked oxygenated Hb (oxy-Hb) concentration change was accompanied by an increase in the deoxy-Hb concentration in the human brain. We found that when a specific brain region was activated by two working memory (WM) task blocks in rapid succession, the local change in the deoxy-Hb concentration evoked by the second task block was reversed to an increase due to the refractory effect in the hemodynamic response. The result suggests that the polarity of the blood oxygenation level-dependent (BOLD) signal could change during repetitive neuronal activation, and thus caution must be taken in the interpretation of the BOLD signal under such situations.

Clinical and imaging characteristics of localized megalencephaly: a retrospective comparison of diffuse hemimegalencephaly and multilobar cortical dysplasia.

INTRODUCTION: Hemimegalencephaly is a well-known congenital malformation. However, localized megalencephaly, which may be one of the subtypes of hemimegalencephaly, has not been separately investigated. In the present study, we attempted to characterize the clinical and magnetic resonance (MR) imaging features of localized megalencephaly in comparison with ordinary diffuse hemimegalencephaly and multilobar cortical dysplasia. METHODS: MR findings for 43 patients with hemimegalencephaly and ten with multilobar cortical dysplasia, which is the differential diagnosis of localized megalencephaly, were retrospectively reviewed. Clinical findings such as the onset and severity of seizures and imaging findings including the affected area of the brain, structures outside of the hemisphere, and interval morphological changes were examined. RESULTS: Of the 43 patients, 11 showed signs of localized megalencephaly (25.6%). Localized megalencephaly was predominantly seen on the left side (72.7%) and had a tendency toward severe-grade seizures compared to multilobar cortical dysplasia. The frequencies of the extracerebral abnormalities in the diffuse hemimegalencephaly, localized megalencephaly, and multilobar cortical dysplasia groups were 84.4%, 36.4%, and 0.0%, respectively. There were three localized megalencephaly patients whose affected areas shrank and whose images were similar to those of multilobar cortical dysplasia. CONCLUSION: Localized megalencephaly accounts for one quarter of all hemimegalencephaly cases in this study. The incidence of extracerebral abnormalities in patients with localized hemimegalencephaly was almost half that of patients with diffuse hemimegalencephaly. Extracerebral abnormalities were absent in patients with multilobar cortical dysplasia. Associated extracerebral abnormalities may be a clue to differentiating localized megalencephaly from multilobar cortical dysplasia.

[Evaluation of exposure dose for panoramic radiography].

PURPOSE: There is no established method to determine a diagnostic reference level of panoramic radiology. As the basic principle of the panoramic radiology dose index (PRDI) and CT dose index (CTDI) is almost identical, we evaluated the usefulness of PRDI for this purpose. METHODS: Using the imaging plate (IP) sandwiched between the 160-mm thick acrylic disks, horizontal radiation dose distribution was analyzed by the conventional radiographic technique. Panoramic exposure dose was measured using the CT ionizing chamber that was placed at the tracking focus. Beam height was used as measurement unit, and PRDI was normalized and calculated. RESULTS: There were two foci showing the maximum exposure dose for this panoramic equipment, located symmetrically 45 mm away from the center of the object. The PRDI of medium-sized individuals measured by this method was 0.74 mGy. CONCLUSION: We suggested a method to evaluate a diagnostic reference level, measuring the dose of exposure focus, i.e., maximum dose on panoramic radiology.