Masakazu Hirakawa

Usefulness of apparent diffusion coefficient map in diagnosing prostate carcinoma: Correlation with stepwise histopathology

To elucidate the performance of apparent diffusion coefficient (ADC) map in localizing prostate carcinoma (PC) using stepwise histopathology as a reference.

Hepatocellular carcinoma with a pseudocapsule on gadolinium-enhanced MR images: correlation with histopathologic findings.

PURPOSE To evaluate the characteristics of hepatocellular carcinoma (HCC) with a pseudocapsule on dynamic magnetic resonance (MR) images. MATERIALS AND METHODS The institutional review board approval was obtained, and the requirements for informed consent were waived for this retrospective study. Dynamic MR studies of surgically resected 106 HCCs in 93 patients were retrospectively reviewed. A false-positive fibrous capsule (FC) on dynamic MR images was considered to be a pseudocapsule. Pathologic specimens of HCCs with a pseudocapsule were reviewed. The differences in size, tumor grade, the degree of liver fibrosis and background liver diseases, and the incidence of vascular invasion were compared between HCCs with a pseudocapsule on MR images and those with FC at histologic examination by using Student t, Kruskal-Wallis, and chi(2) tests. RESULTS The sensitivity, specificity, and accuracy of dynamic MR in the diagnosis of histologic FC were 94.0% (47 of 50), 73.2% (41 of 56), and 83.0% (88 of 106), respectively. There were 15 (14.2%) HCCs with a pseudocapsule. The pathologic specimens suggested possible causes of the pseudocapsule that included prominent sinusoids (n = 6), peritumoral fibrosis mimicking bridging fibrosis (n = 3), and both (n = 5). In one case, the capsulated HCC was surrounded by a well-differentiated HCC component. The mean size of a HCC with a pseudocapsule tended to be smaller than that with histologic FC, although it was not significant (mean +/- standard deviation: 2.8 cm +/- 1.0 vs 3.5 cm +/- 2.0, P = .09). Liver cirrhosis was less frequent in HCCs with a pseudocapsule than in those with a histologic FC (one of 14 [7.1%] vs 20 of 49 [40.8%], P < .05). The tumor grades were not significantly different, and the incidence of vascular invasion after standardizing the tumor size (<or=4 cm) was similar (five of 14 [35.7%] vs 12 of 37 [32.4%]). CONCLUSION Dynamic MR imaging is accurate in depicting FC in HCCs. HCC with a pseudocapsule at MR possibly consists of peritumoral sinusoids and/or fibrosis. The pseudocapsule may be similar to histologic FC in terms of tumor invasiveness.

Sequential activation of RhoA and FAK/paxillin leads to ATP release and actin reorganization in human endothelium

We have investigated the cellular mechanisms of mechanical stress‐induced immediate responses in human umbilical vein endothelial cells (HUVECs). Hypotonic stress (HTS) induced ATP release, which evoked a Ca2+ transient, followed by actin reorganization within a few minutes, in HUVECs. Disruption of the actin cytoskeleton did not suppress HTS‐induced ATP release, and inhibition of the ATP‐mediated Ca2+ response did not affect actin reorganization, thereby indicating that these two responses are not interrelated. ATP release and actin reorganization were also induced by lysophosphatidic acid (LPA). HTS and LPA induced membrane translocation of RhoA, which occurs when RhoA is activated, and tyrosine phosphorylation of focal adhesion kinase (FAK) and paxillin. Tyrosine kinase inhibitors (herbimycin A or tyrphostin 46) inhibited both HTS‐ and LPA‐induced ATP release and actin reorganization, but did not affect RhoA activation. In contrast, Rho‐kinase inhibitor (Y27632) inhibited all of the HTS‐ and LPA‐induced responses. These results indicate that the activation of the RhoA/Rho‐kinase pathway followed by tyrosine phosphorylation of FAK and paxillin leads to ATP release and actin reorganization in HUVECs. Furthermore, the fact that HTS and LPA evoke exactly the same intracellular signals and responses suggests that even these immediate mechanosensitive responses are in fact not mechanical stress‐specific.

Radiologic Detectability of Minute Portal Venous Invasion in Hepatocellular Carcinoma

OBJECTIVE The objective of this study was to evaluate whether minute portal venous invasion in hepatocellular carcinoma (HCC) can be diagnosed radiologically. MATERIALS AND METHODS CT hepatic arteriography and CT with arterioportography (CTAP) of 15 patients with minute portal venous invasion (group 1) and 30 patients without it (group 0) were evaluated. An area showing low attenuation on CTAP and high attenuation on CT hepatic arteriography around the tumor was defined as an area of peritumoral hemodynamic change. The shape and size of the area were compared between the two groups. The ratio of the area of peritumoral hemodynamic change volume to tumor volume (area volume-tumor volume ratio) was used as an indicator of the size of the area of peritumoral hemodynamic change and was categorized as one of three grades: grade I, 10% or less; grade II, between 10% and 30%; and grade III, 30% or more. The detectability of minute portal invasion was assessed when grade III was considered as an indicator. Each comparison was also made independently when the tumor diameter either was limited to less than 3 cm or was 3 cm or more. RESULTS Three types of area of peritumoral hemodynamic change were identified: wedge-shaped, belt-shaped or irregular, and linear. No significant difference in the frequency of each type of area of peritumoral hemodynamic change was observed between the two groups. The area volume-tumor volume ratio in group 1 was larger than that in group 0, with statistical significance when the tumor diameter was less than 3 cm (p = 0.046). Positive and negative predictive values were 71.4% and 75.0%, respectively, when the tumor diameter was less than 3 cm. CONCLUSION The area of peritumoral hemodynamic change in HCC patients with minute portal invasion (group 1) may be larger than in those without it (group 0), especially when tumors are small.

Papillary renal carcinoma: Diagnostic approach by chemical shift gradient-echo and echo-planar MR imaging

To elucidate whether MRI can detect fat in interstitial histiocytes and hemosiderin (Hs) deposition (both of which are histological characteristics of papillary renal carcinoma (RCpap)) within RCpap.

Hypovascular hepatic nodule showing hypointensity in the hepatobiliary phase of gadoxetic acid-enhanced MRI in patients with chronic liver disease: Prediction of malignant transformation

PURPOSE To investigate the predictive factors of malignant transformation of hypovascular hepatic nodule showing hypointensity in the hepatobiliary phase images of gadoxetic acid-enhanced MRI (HHN). MATERIALS AND METHODS The clinical data and imaging findings of dynamic contrast-enhanced computed tomography (DCE-CT) and gadoxetic acid-enhanced MRI for a total of 103 HHNs in 24 patients with chronic liver disease were retrospectively investigated. After the results of follow-up examinations were investigated, HHNs were categorized into the three groups for each comparison: (1) nodules with enlargement and/or vascularization and others, (2) nodules with only enlargement and others, (3) nodules with only vascularization and others. Enlargement and/or vascularization during the follow-up period were defined as malignant transformation of HHN. The frequency of each clinical datum and imaging finding in each group was compared to identify the predictive factors for malignant transformation in HHN. RESULTS Multivariate analysis showed that a nodule size of 9 mm or more on the initial gadoxetic acid-enhanced MRI was a significant predictive factor for the enlargement and/or vascularization of HHN (P<0.05). On the other hand, the hypoattenuation on the delayed phase imaging of the initial DCE-CT was a significant predictive factor for the enlargement or vascularization of HHN (P<0.05). CONCLUSION A nodule size of 9 mm or more on the initial gadoxetic acid-enhanced MRI and hypoattenuation on the delayed phase imaging of initial DCE-CT would be helpful for predicting the outcome of HHN in patients with a risk of hepatocellular carcinoma.

Detection of hepatocellular carcinoma (HCC) using super paramagnetic iron oxide (SPIO)-enhanced MRI: Added value of diffusion-weighted imaging (DWI)

To evaluate whether diffusion‐weighted imaging (DWI) improves the detection of hepatocellular carcinoma (HCC) on super paramagnetic iron oxide (SPIO)‐enhanced MRI.

Noninvasive estimation of hepatic steatosis using plain CT vs. Chemical-shift MR imaging: Significance for living donors

To compare plain computed tomography (CT) and chemical‐shift MR imaging (CSI) for establishing a noninvasive method to estimate the degree of steatosis.

Uterine artery embolization along with the administration of methotrexate for cervical ectopic pregnancy: technical and clinical outcomes.

OBJECTIVE The objective of our study was to evaluate the technical and clinical outcomes of uterine artery embolization (UAE) along with the administration of methotrexate (MTX) for cervical ectopic pregnancy with vaginal bleeding as an alternative nonsurgical treatment to control bleeding and preserve fertility. MATERIALS AND METHODS Eight patients (age range, 24-37 years; mean age, 30.1 years) with cervical ectopic pregnancy were treated with UAE using gelatin sponge particles to control vaginal bleeding. In seven patients, the administration of MTX was performed before, after, or before and after UAE. The follow-up periods after UAE ranged from 4 to 46 months (median, 8 months). We evaluated the UAE technique, clinical outcomes, complications, and fertility. RESULTS In all patients, UAE could control active vaginal bleeding on gynecologic examination. In six patients, the cervical ectopic pregnancy was dramatically resolved. In the other two patients presenting with both fetal heartbeat before UAE and persistent high HCG levels, active vaginal rebleeding was observed. The rebleeding was successfully controlled by a second UAE procedure. No major complication related to UAE was detected. The uterus could be preserved in all patients. In seven patients, normal menses resumed within 2 months after UAE. In only one patient, amenorrhea continued 8 months after UAE. In all three patients who could be followed for 2 years or more, three had subsequent successful natural pregnancies, and two patients had live births. CONCLUSION UAE along with the administration of MTX is effective in treating cervical ectopic pregnancy with vaginal bleeding while allowing the preservation of fertility.

Decreased Expression of Fructose-1,6-bisphosphatase Associates with Glucose Metabolism and Tumor Progression in Hepatocellular Carcinoma

Fructose-1,6-bisphosphatase (FBP1), the rate-limiting enzyme in gluconeogenesis, is reduced in expression in certain cancers where it has been hypothesized to act as a tumor suppressor, including in hepatocellular carcinoma (HCC). Here, we report functional evidence supporting this hypothesis, providing a preclinical rationale to develop FBP1 as a therapeutic target for HCC treatment. Three independent cohorts totaling 594 cases of HCC were analyzed to address clinical significance. Lower FBP1 expression associated with advanced tumor stage, poor overall survival, and higher tumor recurrence rates. In HCC cell lines, where endogenous FBP1 expression is low, engineering its ectopic overexpression inhibited tumor growth and intracellular glucose uptake by reducing aerobic glycolysis. In patient specimens, promoter methylation and copy-number loss of FBP1 were independently associated with decreased FBP1 expression. Similarly, FBP1 downregulation in HCC cell lines was also associated with copy-number loss. HCC specimens exhibiting low expression of FBP1 had a highly malignant phenotype, including large tumor size, poor differentiation, impaired gluconeogenesis, and enhanced aerobic glycolysis. The effects of FBP1 expression on prognosis and glucose metabolism were confirmed by gene set enrichment analysis. Overall, our findings established that FBP1 downregulation in HCC contributed to tumor progression and poor prognosis by altering glucose metabolism, and they rationalize further study of FBP1 as a prognostic biomarker and therapeutic target in HCC patients. Cancer Res; 76(11); 3265-76. ©2016 AACR.