Effect of Oral Alfacalcidol on Clinical Outcomes in Patients Without Secondary Hyperparathyroidism Receiving Maintenance Hemodialysis: The J-DAVID Randomized Clinical Trial.

Importance: Patients with chronic kidney disease have impaired vitamin D activation and elevated cardiovascular risk. Observational studies in patients treated with hemodialysis showed that the use of active vitamin D sterols was associated with lower risk of all-cause mortality, regardless of parathyroid hormone levels. Objective: To determine whether vitamin D receptor activators reduce cardiovascular events and mortality in patients without secondary hyperparathyroidism undergoing hemodialysis. Design, Setting, and Participants: Randomized, open-label, blinded end point multicenter study of 1289 patients in 207 dialysis centers in Japan. The study included 976 patients receiving maintenance hemodialysis with serum intact parathyroid hormone levels less than or equal to 180 pg/mL. The first and last participants were enrolled on August 18, 2008, and January 26, 2011, respectively. The final date of follow-up was April 4, 2015. Interventions: Treatment with 0.5 µg of oral alfacalcidol per day (intervention group; n = 495) vs treatment without vitamin D receptor activators (control group; n = 481). Main Outcomes and Measures: The primary outcome was a composite measure of fatal and nonfatal cardiovascular events, including myocardial infarctions, hospitalizations for congestive heart failure, stroke, aortic dissection/rupture, amputation of lower limb due to ischemia, and cardiac sudden death; coronary revascularization; and leg artery revascularization during 48 months of follow-up. The secondary outcome was all-cause death. Results: Among 976 patients who were randomized from 108 dialysis centers, 964 patients were included in the intention-to-treat analysis (median age, 65 years; 386 women [40.0%]), and 944 (97.9%) completed the trial. During follow-up (median, 4.0 years), the primary composite outcome of cardiovascular events occurred in 103 of 488 patients (21.1%) in the intervention group and 85 of 476 patients (17.9%) in the control group (absolute difference, 3.25% [95% CI, -1.75% to 8.24%]; hazard ratio, 1.25 [95% CI, 0.94-1.67]; P = .13). There was no significant difference in the secondary outcome of all-cause mortality between the groups (18.2% vs 16.8%, respectively; hazard ratio, 1.12 [95% CI, 0.83-1.52]; P = .46). Of the 488 participants in the intervention group, 199 (40.8%) experienced serious adverse events that were classified as cardiovascular, 64 (13.1%) experienced adverse events classified as infection, and 22 (4.5%) experienced malignancy-related serious adverse events. Of 476 participants in the control group, 191 (40.1%) experienced cardiovascular-related serious adverse events, 63 (13.2%) experienced infection-related serious adverse events, and 21 (4.4%) experienced malignancy-related adverse events. Conclusions and Relevance: Among patients without secondary hyperparathyroidism undergoing maintenance hemodialysis, oral alfacalcidol compared with usual care did not reduce the risk of a composite measure of select cardiovascular events. These findings do not support the use of vitamin D receptor activators for patients such as these. Trial Registration: UMIN-CTR Identifier: UMIN000001194.

Value of EUS in early detection of pancreatic ductal adenocarcinomas in patients with intraductal papillary mucinous neoplasms.

BACKGROUND AND STUDY AIMS: Pancreatic ductal adenocarcinomas (PDAC) sometimes arise in patients with intraductal papillary mucinous neoplasms (IPMNs). This study examined the incidence of PDACs concomitant to or derived from branch duct IPMNs. The usefulness of endoscopic ultrasonography (EUS) relative to other imaging methods for detecting these tumors was also assessed. PATIENTS AND METHODS: This retrospective study used data from clinical records and imaging studies that were collected prospectively. During 2001-2009, 167 consecutive patients with IPMNs underwent EUS, ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI). The 102 patients whose branch duct IPMNs lacked mural nodules/symptoms and thus did not qualify for resection were followed up by semiannual EUS and annual ultrasonography, CT, and MRI. The sensitivity and specificity with which the four modalities detected IPMN-derived and -concomitant PDACs at the first examination and throughout the study period were evaluated. The rate of PDAC development during follow-up was analyzed by the Kaplan-Meier method. RESULTS: A total of 17 IPMN-derived and 11 IPMN-concomitant PDACs were diagnosed at the first examination. Lesions that did not qualify for resection or chemotherapy were followed up for a median of 42 months. Seven IPMN-concomitant PDACs and no IPMN-derived PDACs were detected during follow-up. The 3- and 5-year rates of IPMN-concomitant PDAC development were 4.0% and 8.8%, respectively. At the first examination, EUS was superior to other imaging modalities in terms of IPMN-derived and -concomitant PDAC detection. Throughout the study period, including follow-up, EUS was significantly better at detecting IPMN-concomitant PDACs than the other modalities. CONCLUSIONS: IPMN-concomitant PDACs are quite often found at diagnosis and during follow-up. EUS examination of the whole pancreas plays an important role in the management of IPMNs as it allows the early detection of these small invasive carcinomas.

Impact of atherosclerosis on the relationship of glycemic control and mortality in diabetic patients on hemodialysis.

OBJECTIVE: The impact of preexisting cardiovascular disease (CVD) on glycemic control-improved survival in hemodialysis patients with diabetes mellitus (DM) was investigated. Glycoalbumin (GA) was used as a glycemic marker. METHODS: A single-center 4-year follow-up study was performed in an observational cohort of 178 DM hemodialysis patients to analyze the relationship between GA and all-cause mortality in patients with (n = 70) and without (n = 108) CVD. The subjects were divided into three categories based on GA value at the start of study. RESULTS: Baseline characteristics did not differ between the two groups of patients. During the 4-year follow-up, 24 of 108 (23.3%) CVD(-) patients and 30 of 70 (42.8%) CVD(+) patients died. The mortality was significantly higher in the CVD(+) group. Multivariate Cox analyses including GA, logCRP, age, gender, hemodialysis duration, albumin, hemoglobin, BMI, SBP, DBP, smoking habit, and SUN as independent variables showed that GA, in addition to logCRP and age, was independently associated with mortality in all patients. Kaplan-Meier analysis showed lower GA levels to be a significant predictor of lower mortality in the CVD(-) group, but not in the CVD(+) group. Multivariable-adjusted Cox proportional hazards models demonstrated a significant association between GA with allcause mortality risk in the CVD(-) group (p = 0.004), in contrast with the CVD(+) group in the same model (p = 0.842). CONCLUSION: These results demonstrate a beneficial effect of improved glycemic control on survival in DM hemodialysis patients, which might be attenuated by the presence of CVD.

Comparative Effects of Etelcalcetide and Maxacalcitol on Serum Calcification Propensity in Secondary Hyperparathyroidism: A Randomized Clinical Trial.

BACKGROUND AND OBJECTIVES: Vitamin D receptor activators and calcimimetics (calcium-sensing receptor agonists) are two major options for medical treatment of secondary hyperparathyroidism. A higher serum calcification propensity (a shorter T50 value) is a novel surrogate marker of calcification stress and mortality in patients with CKD. We tested a hypothesis that a calcimimetic agent etelcalcetide is more effective in increasing T50 value than a vitamin D receptor activator maxacalcitol. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A randomized, multicenter, open-label, blinded end point trial with active control was conducted in patients with secondary hyperparathyroidism undergoing hemodialysis in Japan. Patients were randomly assigned to receive intravenous etelcalcetide 5 mg thrice weekly (etelcalcetide group) or intravenous maxacalcitol 5 or 10 µg thrice weekly (maxacalcitol group). The primary, secondary, and tertiary outcomes were changes in T50 value, handgrip strength, and score of the Dementia Assessment Sheet for Community-Based Integrated Care System from baseline to 12 months, respectively. RESULTS: In total, 425 patients from 23 dialysis centers were screened for eligibility, 326 patients were randomized (etelcalcetide, n=167; control, n=159), and 321 were included in the intention-to-treat analysis (median age, 66 years; 113 women [35%]). The median (interquartile range) of T50 value was changed from 116 minutes (interquartile range, 90-151) to 131 minutes (interquartile range, 102-176) in the maxacalcitol group, whereas it was changed from 123 minutes (interquartile range, 98-174) to 166 minutes (interquartile range, 127-218) in the etelcalcetide group. The increase in T50 value was significantly greater in the etelcalcetide group (difference in change, 20 minutes; 95% confidence interval, 7 to 34 minutes; P=0.004). No significant between-group difference was found in the change in handgrip strength or in the Dementia Assessment Sheet for Community-Based Integrated Care System score. CONCLUSIONS: Etelcalcetide was more effective in increasing T50 value than maxacalcitol among patients on hemodialysis with secondary hyperparathyroidism. There was no difference in handgrip strength or cognition between the two drugs. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: VICTORY; UMIN000030636 and jRCTs051180156.

Newly developed novel ultrasound technique, defect reperfusion ultrasound imaging, using sonazoid in the management of hepatocellular carcinoma.

The aim of this study is to clarify the usefulness of defect reperfusion ultrasound (US) imaging using Sonazoid in the management of hepatocellular carcinoma (HCC). A total of 33 HCC nodules and 34 local recurring nodules after radiofrequency ablation (RFA), which could not be identified by B-mode US but were depicted by dynamic CT, were studied by defect reperfusion US imaging with Sonazoid. In addition, Kupffer phase Sonazoid-enhanced US in combination with defect reperfusion US imaging were used for screening HCC in 262 consecutive cirrhotic patients. As a result, 33 US undetectable HCC nodules and 34 local recurring HCC nodules were successfully confirmed by Sonazoid-enhanced US with defect reperfusion imaging. Subsequently, RFA was successfully performed in all of 67 HCC nodules with a Sonazoid-enhanced US guidance. A total of 7 small HCCs were depicted and confirmed as HCCs by Kupffer phase surveillance and defect reperfusion US imaging. In conclusion, defect reperfusion US imaging is extremely useful in the depiction and confirmation of US undetectable HCCs as well as in the surveillance of HCC in cirrhotic patients.

Depiction of portal supply in early hepatocellular carcinoma and dysplastic nodule: value of pure arterial ultrasound imaging in hepatocellular carcinoma.

Ultrasound (US) contrast agents such as SonoVue and Sonazoid are commercially available worldwide. Innovation of contrast agents and advances of new US technologies have dramatically changed both diagnostic and treatment strategies for hepatocellular carcinoma (HCC). Recently, the breakthrough technique, pure arterial phase (PAP) US imaging, which depicts only intranodular arterial supply by use of maximum intensity projection (MIP) images, was developed from advanced raw data-storing and accumulation technologies. A total of 8 dysplastic nodules (DNs), 16 early HCCs, 5 nodule-in-nodule type early HCCs and 48 overt HCCs were included in this study. All 8 DNs (100%) showed arterial hypovascularity in the PAP followed by preserved portal perfusion at the portal phase and isouptake at the Kupffer phase by Sonazoid-enhanced contrast US. A total of 12 out of 16 early HCCs (75%) showed similar patterns on vascular and Kupffer phase imaging of contrast-enhanced ultrasonography. The remaining 4 HCCs showed slightly hypervascular pattern without venous washout and slightly decreased Kupffer uptake. All 5 nodule-in-nodule type early HCCs presented partial arterial enhancement within hypovascular nodule at the PAP followed by isovascular pattern at the portal phase and partial Kupffer defect within isouptake nodules. All 48 overt HCCs showed a hypervascular pattern with Kupffer defect on contrast-enhanced ultrasonography. This technique can clearly identify whether blood supply in the tumor is of arterial or portal origin, and facilitate the noninvasive characterization of nodular lesions associated with liver cirrhosis. In conclusion, this newly developed innovative technique can depict pure portal supply in early HCC and DN, enabling differentiating premalignant lesions and early HCCs from overt HCC even though dynamic CT or MRI does not have such capabilities.

Contrast-enhanced ultrasound techniques for guiding and assessing response to locoregional treatments for hepatocellular carcinoma.

Most hepatocellular carcinomas (HCC) are diagnosed in patients with cirrhosis and/or when tumor burden is too advanced for surgical treatment. In many of these cases the only suitable therapy is locoregional, percutaneous and/or intraarterial treatment. Moreover, the best way to guide and assess response to locoregional HCC treatment are two issues under discussion today. First-generation and subsequent second-generation microbubble contrast agents, together with contrast-enhanced ultrasound (US) imaging, have expanded the role of US techniques in HCC treatments. In this review our purpose is to illustrate the advantages, limits and potential of contrast-enhanced US application for locoregional HCC treatment.

Usefulness of the post-vascular phase of contrast-enhanced ultrasonography with sonazoid in the evaluation of gross types of hepatocellular carcinoma.

OBJECTIVE: The purpose of this study was to assess the usefulness of post-vascular phase (PVP) images of contrast-enhanced ultrasonography (CE-US) in the evaluation of the gross types of hepatocellular carcinoma (HCC) that is closely related to the malignant potential of the tumor. METHODS: A total of 29 patients with 40 HCCs of <5 cm in diameter, who underwent hepatic resection, were enrolled. The gross type of the tumor was evaluated using real-time scanning during the PVP of CE-US with Sonazoid prior to surgery. The tumors were classified into three types based on the macroscopic classification of the Liver Cancer Study Group of Japan: single nodular (SN) type, single nodular with extranodular growth (SNEG) type, and confluent multinodular (CMN) type. The ability of CE-US to correctly depict the gross type of HCC was evaluated. RESULTS: 26 tumors were macroscopically diagnosed as the SN type, 11 tumors as the SNEG type, and 3 tumors as the CMN type. The sensitivity, specificity and accuracy of CE-US were 96, 80 and 90%, respectively. CONCLUSION: The PVP image of CE-US with Sonazoid is a useful tool in the evaluation of the gross type of HCC and is considered essential in deciding treatment strategy.

Non-invasive evaluation of hepatic fibrosis for type C chronic hepatitis.

OBJECTIVE: The aim of this study was to investigate liver fibrosis using non-invasive Real-time Tissue Elastography (RTE) and transient elastography (FibroScan) methods. METHODS: RTE, FibroScan and percutaneous liver biopsy were all performed on patients with chronic liver disease, particularly hepatitis C, to investigate liver fibrosis. RESULTS: FibroScan and RTE were compared for fibrous liver staging (F stage), which was pathologically classified using liver biopsy. In FibroScan, significant differences were observed between F1/F3 and F2/F4, but no such differences were observed between F1/F2, F2/F3 and F3/F4. In RTE, significant differences were observed between F1/F2, F2/F3 and F2/F4. But for F3/F4, no significant differences were observed. CONCLUSION: FibroScan and RTE correlated well with F staging of the liver. In particular RTE was more successful than FibroScan in diagnosing the degree of liver fibrosis.

Decreases in parathyroid gland volume after cinacalcet treatment in hemodialysis patients with secondary hyperparathyroidism.

BACKGROUND/AIM: Cinacalcet, an allosteric modulator of the calcium-sensing receptor, effectively reduces serum parathyroid hormone (PTH). It was examined whether a regression of parathyroid glands in hemodialysis patients with secondary hyperparathyroidism was induced by cinacalcet treatment. METHODS: Ultrasonography of the parathyroid glands was performed to examine the changes in the parathyroid gland volumes after cinacalcet treatment in 58 patients. RESULTS: After cinacalcet treatment, serum calcium, phosphate, alkaline phosphatase, and intact PTH significantly decreased (p < 0.0001). The total volumes of the parathyroid glands were significantly decreased 6 months after cinacalcet treatment (942 +/- 747 vs. 708 +/- 550 mm(3), p < 0.0005). There was a significant positive correlation between the parathyroid gland volumes at the start of cinacalcet treatment and the volume reduction in parathyroid glands (r = 0.716, p < 0.0001). Of the 58 patients, the total parathyroid gland volume was decreased in 42 patients and increased in 16 although the doses of cinacalcet, phosphate binders or vitamin D were not significantly different. In both groups, the intact PTH serum levels were significantly decreased after cinacalcet treatment. CONCLUSION: Cinacalcet treatment in patients with secondary hyperparathyroidism significantly reduced the total parathyroid gland volume in a short 6-month period. This study suggests that cinacalcet treatment may postpone parathyroidectomy and/or reduce cases.

Recurrent abdominal pain caused by nephroptosis.

Nephroptosis is a benign disorder defined as a significant descent of the affected kidney as the patient moves from supine to erect. Patients with nephroptosis sometimes manifest symptoms including abdominal pain, back pain, nausea and hematuria, while the majority of those are asymptomatic. Downward migration of the affected kidney induced by a postural change from the supine to the upright position underlies the pathophysiology of nephroptosis. The diagnosis of nephroptosis is difficult since routine imaging examinations are conducted in the supine position alone. Here, we report a case presenting recurrent abdominal pain due to unknown causes. This patient was successfully diagnosed as nephroptosis by ultrasonography and drip infusion pyelography, both of which were performed in both supine and upright positions. This case report strongly suggests that we need to take into consideration a possibility of nephroptosis when we encounter with patients complaining abdominal and/or back pain due to unknown causes.

Association of reduction in bone mineral density with mortality in male hemodialysis patients.

In the present study we examined the relationship of bone mineral density (BMD) reduction with increased mortality in hemodialysis patients. A single-center prospective observational study was conducted on 269 male hemodialysis patients. The BMD in the distal third of the radius (DR1/3) and in the ultradistal radius (UR), which are enriched with cortical and cancellous bone, respectively, was measured twice using dual-energy X-ray absorptiometry (DXA) with a 1-year interval. Subjects were divided into two groups based on the presence or absence of BMD reduction. Survival was followed for 61.0 months, after which time 104 patients (39%) had died. A significant BMD reduction at the UR and DR1/3 occurred in 182 (68%) and 195 (72%) patients, respectively. Patients with BMD reduction in the UR, in contrast to the DR1/3, had a significantly lower survival rate than those without BMD reduction (P = 0.01). In Cox regression analysis, the rate of BMD change at the UR, in addition to patient age, diabetes mellitus, and serum albumin, emerged as an independent predictor for increased mortality (HR = 0.970, 95% CI 0.945-0.996). Our results suggest that BMD reduction at the UR might be a clinically relevant marker that predicts an increased risk of mortality in male hemodialysis patients.

Significant association of fracture of the lumbar spine with mortality in female hemodialysis patients: a prospective observational study.

Prevalent fracture of the lumbar spine is established as a predictor of increased mortality in the general population. To examine whether this association is retained in hemodialysis patients, we conducted a single-center prospective observational study in 635 hemodialysis patients (60.3 + or - 12.0 years old, male/female 369/266). Patients were divided into two groups (with and without lumbar fracture, assessed by simple lateral radiograph), and survival was followed for an average of 53.8 months. Lumbar fracture was present in 62 patients (9.76%; male 9.76%, female 9.77%). During the follow-up period, there were 176 all-cause deaths (27.7%; male 27.6%, female 27.8%), of which 72 were from cardiovascular diseases. In Kaplan-Meier analysis, all-cause and noncardiovascular mortality rates, but not cardiovascular mortality, were significantly higher in patients with fracture than in those without (P < 0.0001). In multivariate Cox proportional hazard analysis, the presence of lumbar fracture was significantly associated with increased noncardiovascular mortality (HR = 2.035, 95% CI 1.135-3.652, P < 0.05) after adjustment for age, duration of hemodialysis, presence of diabetes, body mass index, and serum calcium, phosphate, and albumin. Significantly higher all-cause and noncardiovascular mortality rates were also evident for patients with fracture in separate analyses in males and females, but multivariate analysis showed a significant association of lumbar fracture with increased all-cause (HR = 2.151, 95% CI 1.033-4.478, P < 0.05) and noncardiovascular (HR = 2.637, 95% CI 1.014-6.858, P < 0.05) mortality rates only in females. In conclusion, lumbar fracture is significantly associated with all-cause mortality in female patients.

Value of liver parenchymal phase contrast-enhanced sonography to diagnose premalignant and borderline lesions and overt hepatocellular carcinoma.

OBJECTIVE: The objective of our study was to investigate whether liver parenchymal phase contrast-enhanced sonography can provide additional information for assessing histologic grades of hepatocellular carcinoma (HCC). SUBJECTS AND METHODS: Contrast-enhanced sonography using Levovist of 50 hepatic nodules was performed. The vascular and liver parenchymal perfusion patterns were evaluated. The sensitivity, specificity, and accuracy of the histologic diagnosis of the tumors using vascular phase imaging only and systematically combined vascular phase imaging with liver parenchymal phase imaging were calculated. We also performed histologic examination and immunostaining for the detection of Kupffer cells and calculated the Kupffer cell count in the tumorous tissue relative to that in the nontumorous tissue (Kupffer cell ratio) and quantitatively evaluated the relationship between the Kupffer cell ratio and the perfusion patterns seen on liver parenchymal phase imaging. RESULTS: The specificity and accuracy of contrast-enhanced sonography in the diagnosis of dysplastic nodules and of moderately and poorly differentiated HCCs were improved by adding liver parenchymal phase imaging (dysplastic nodules, 74% and 78% vs 83% and 86%, respectively; moderately and poorly differentiated HCCs, 74% and 86% vs 85% and 92%). The diagnostic accuracy of contrast-enhanced sonography for dysplastic nodules showed a trend of improvement with the addition of liver parenchymal phase imaging (p = 0.07). Kupffer cell ratios for tumors that showed hypoperfusion during the liver parenchymal phase were significantly lower than those for tumors showing isoperfusion (p < 0.05). CONCLUSION: Adding liver parenchymal phase imaging to contrast-enhanced sonography protocols may yield additional information that can be used to assess histologic grades of tumor and that leads to an improvement in the differential diagnosis of nodular lesions associated with the cirrhotic liver. Further case studies are required in larger numbers of patients for a longer follow-up period.

Sonazoid-enhanced ultrasonography for diagnosis of hepatic malignancies: comparison with contrast-enhanced CT.

OBJECTIVE: The purpose of this study was to assess the usefulness of Sonazoid-enhanced ultrasonography (US) in the diagnosis of hepatic malignancies in comparison with contrast-enhanced CT findings. METHODS: A total of 74 patients with 113 hepatic tumors having or highly suspected of having malignancies were enrolled. These hepatic nodules were diagnosed by typical findings of imaging such as contrast-enhanced CT, dynamic MRI or Sonazoid-enhanced US, tumor markers and histological examinations after surgical resection or biopsy. RESULTS: 108 nodules were diagnosed as malignant tumors (hepatocellular carcinoma: n = 90; metastasis: n = 16; intrahepatic cholangiocarcinoma: n = 2) and the remaining five tumors were diagnosed as benign tumors (dysplastic nodules: n = 5). Sonazoid-enhanced US correctly depicted the presence or absence of tumors in 74 patients, with a sensitivity of 95.4%, an accuracy of 94.7%, and a positive predictive rate of 99%. Contrast-enhanced CT depicted the malignancies with a sensitivity of 85.2%, an accuracy of 82.3%, and a positive predictive rate of 95.8%. There were significant differences between Sonazoid-enhanced US and contrast-enhanced CT for sensitivity and accuracy (both p < 0.05). CONCLUSION: Sonazoid-enhanced US has a higher sensitivity and accuracy for the diagnosis of hepatic malignancies than contrast-enhanced CT.

Imaging of hepatocellular carcinoma: qualitative and quantitative analysis of postvascular phase contrast-enhanced ultrasonography with sonazoid. Comparison with superparamagnetic iron oxide magnetic resonance images.

PURPOSE: To evaluate the usefulness of vascular phase images of contrast-enhanced ultrasonography (CE-US) with Sonazoid for hepatocellular carcinomas (HCCs), a retrospective, comparative study was conducted of images of HCCs obtained by CE-US and superparamagnetic iron oxide (SPIO) magnetic resonance imaging (MRI) and evaluated qualitatively and quantitatively. METHODS: Seventy-seven patients with 88 HCCs who received CE-US and SPIO-MRI were reviewed. The ratio of the echogenicity of the tumor and nontumor areas was calculated with postvascular phase CE-US (postvascular phase ratio). The ratio of the intensity of the nontumor to tumor areas on SPIO-enhanced MRI (SPIO intensity index) was also calculated. The Pearson correlations were calculated for all values between the postvascular phase ratio and SPIO intensity index for quantitative comparison. These images were also compared qualitatively for the detection rate of the tumors. RESULTS: The sensitivities of CE-US and SPIO-MRI in detecting tumors were 98 and 95%, respectively (nonsignificant, chi(2) test). The postvascular phase ratio correlated with the SPIO intensity index for HCCs (Pearson r = 0.803, p < 0.05). The image conformity of the result from the liver parenchymal phase CE-US and SPIO-MRI was 92%. Dedifferentiation spots of nodule-in-nodule HCCs were detected in 4 (80%) of 5 on postvascular phase images of CE-US, and in 2 (40%) of 5 on SPIO-MRI (nonsignificant, chi(2) test). CONCLUSIONS: Postvascular phase images of CE-US with Sonazoid appear promising as an alternative to SPIO-enhanced MRI. Further study cases are needed to confirm the usefulness of postvascular phase images of CE-US compared to SPIO-MRI for the detection of dedifferentiation foci in hepatic tumors.

Response evaluation of transcatheter arterial chemoembolization in hepatocellular carcinomas: the usefulness of sonazoid-enhanced harmonic sonography.

BACKGROUND: The purpose of this study was to investigate if Sonazoid-enhanced harmonic ultrasonography (US) could be used to evaluate the responses of hepatocellular carcinomas (HCCs) to treatment with transcatheter arterial chemoembolization (TACE). PATIENTS AND METHODS: Forty-three HCCs that had been treated by TACE were evaluated by Sonazoid-enhanced harmonic US and dynamic computed tomography (CT) approximately 1 week after their treatment. The detection rates of residual tumor blood supply using the two modalities were compared. Two months after chemoembolization, 16 of the 43 HCCs, which had no additional local treatment, were followed up with dynamic CT. The results of contrast-enhanced harmonic US and dynamic CT 1 week after chemoembolization were analyzed and compared with follow-up dynamic CT results. RESULTS: The detection rates of positive enhancement with Sonazoid-enhanced harmonic US and dynamic CT 1 week after TACE were 25 (58.1%) of 43 lesions and 17 (39.5%) of 43 lesions, respectively. Sonazoid-enhanced harmonic US was significantly more sensitive than dynamic CT in depicting the residual tumor blood supply to HCCs 1 week after TACE (p < 0.01; chi(2) test). The Sonazoid-enhanced harmonic US results of the 16 lesions 1 week after chemoembolization were consistent with the follow-up results of dynamic CT 2 months after chemoembolization. CONCLUSIONS: Sonazoid-enhanced harmonic US appears to be a highly sensitive and accurate modality for evaluating responses of HCCs shortly after TACE.

Influence of atherosclerosis on the relationship between anaemia and mortality risk in haemodialysis patients.

BACKGROUND: Full, as compared with partial, correction of anaemia did not reduce the mortality risk in patients with chronic kidney disease (CKD), although the underlying mechanisms are unknown. Since CKD is a high-risk population for cardiovascular disease (CVD), we tested a hypothesis that the presence of atherosclerosis affects the relationship between anaemia and mortality risk. METHODS: We performed a single-centre 10-year follow-up study with an observational cohort of 505 haemodialysis patients to analyse the relationship between haematocrit and all-cause mortality. Baseline haematocrit levels did not differ between the 153 patients with CVD and the 352 patients without CVD. RESULTS: During the follow-up, 268 patients died. Both Kaplan-Meier and univariate Cox analyses showed that higher haematocrit levels were a significant predictor of lower risk of death in the CVD (-) group, whereas haematocrit did not predict death in the CVD (+) group. In multivariate Cox analyses, the inverse relationship between haematocrit and mortality in the CVD (-) group remained significant and independent of 14 covariates including the use of erythropoietin. In contrast, using the same Cox models, the CVD (+) group did not show such a beneficial effect of higher haematocrit. Similar observations were made when the subjects were divided based on carotid artery intima-media thickness instead of the presence of CVD. CONCLUSIONS: These results support the hypothesis that the presence of atherosclerosis alters the relationship between anaemia and mortality risk in haemodialysis patients.

Noninvasive evaluation of hepatic fibrosis using serum fibrotic markers, transient elastography (FibroScan) and real-time tissue elastography.

OBJECTIVE: The aim of this study was to investigate the accuracy of noninvasive tests, e.g. serum fibrotic markers, transient elastography and real-time tissue elastography, in the diagnosis of hepatic fibrosis, and to determine whether they can replace liver biopsy. METHODS: 119 patients with chronic liver disease were included in this study. Serum fibrotic markers including hyaluronic acid, type IV collagen, type IV collagen 7S domain and type III procollagen-N-peptide were measured. Aspartate aminotransferase (AST) and platelet counts were also measured to calculate the AST to platelet ratio index (APRI). Liver stiffness was measured using FibroScan and real-time tissue elastography. RESULTS: The fibrotic stage, determined by histopathological diagnosis of a liver biopsy sample, did not correlate as well with serum fibrotic markers although it was useful to diagnose liver cirrhosis. However, the stage of hepatic fibrosis correlated well with liver stiffness measured by FibroScan. FibroScan was also a much better predictor of liver cirrhosis than APRI. Furthermore, the levels of liver strain measured by real-time tissue elastography correlated well with liver stiffness (p < 0.05). CONCLUSION: Serum fibrotic markers and FibroScan are useful for distinguishing liver cirrhosis (F4) from chronic hepatitis (F1-F3). In addition, real-time tissue elastography is a novel and promising method to determine the stage of hepatic fibrosis.

Differential diagnosis of hepatic tumors: value of contrast-enhanced harmonic sonography using the newly developed contrast agent, Sonazoid.

OBJECTIVE: To clarify the value of contrast-enhanced harmonic ultrasonography (US) with Sonazoid, a second-generation US contrast agent, in the differential diagnosis of liver tumors compared to dynamic CT. METHODS: A total of 249 hepatic nodules in 214 patients were studied; these included 177 hepatocellular carcinomas (HCCs), 42 liver metastases, 20 liver hemangiomas, 6 dysplastic nodules and 4 focal nodular hyperplasias (FNHs). After the injection of Sonazoid, nodules were scanned using real-time contrast-enhanced harmonic US in the vascular phases, i.e. the early and late vascular phases, and the Kupffer phase. RESULTS: Six enhancement patterns were identified to be significant for the differential diagnosis of hepatic tumors. In HCCs, the presence of intratumoral vessels supplied from the periphery and fast washout (sensitivity, 96.6%; specificity, 94.4%) were the most typical characteristics. In metastases, the presence of rim-like enhancement with peripheral tumor vessels (sensitivity, 88.1%; specificity, 100%) was the typical pattern. In hemangiomas, the presence of intratumoral hypoperfusion images with globular or cotton wool-like pooling, which continue to the late vascular phase (sensitivity, 90.0%; specificity, 99.6%), was typical. In dysplastic nodules, the presence of portal enhancement without arterial supply in the early vascular phase and the presence of intratumoral uptake in the Kupffer phase (sensitivity, 83.3%; specificity, 100%) were the most typical patterns. In FNHs, the presence of a spoke-wheel pattern in the early vascular phase with dense staining in the late vascular phase, and positive uptake within the nodule in the Kupffer phase (sensitivity, 100%; specificity, 100%) were the most typical patterns. CONCLUSION: Contrast-enhanced harmonic US with Sonazoid allowed intimate vascular and Kupffer imaging and, therefore, is useful for the differential diagnosis of hepatic tumors.