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Esophageal squamous cell carcinoma (ESCC) often recurs after chemoradiotherapy, and the prognosis of ESCC after chemoradiotherapy has not improved over the past few decades. The mutation process in chemoradiotherapy-resistant clones and the functional relevance of genetic alterations remain unclear. To address these problems, we performed whole-exome sequencing of 52 tumor samples from 33 patients with ESCC who received radiotherapy combined with 5-fluorouracil/platinum. In multiregion analyses of pretreatment and locally recurrent lesions from five cases, most driver gene-altered clones remained under chemoradiotherapy selection pressure, while few driver gene alterations were acquired at recurrence. The mutation signatures of recurrent ESCC, including increased deletion frequency and platinum dose-dependent base substitution signatures, were substantially different from those of primary ESCC and reflected the iatrogenic impacts of chemoradiotherapy. Single-region analysis of 28 pretreatment tumors indicated that focal copy-number gain at the MYC locus was significantly associated with poor progression-free survival and overall survival after chemoradiotherapy. MYC gain remained throughout the chemoradiotherapy course and potentially contributes to intrinsic resistance to chemoradiotherapy. Consistent with these findings, MYC copy number and mRNA and protein levels in ESCC cell lines correlated positively with resistance to radiotherapy, and MYC knockdown improved sensitivity to radiotherapy. Overall, these data characterize the clonal evolution process induced by chemoradiotherapy and clinically relevant associations for genetic alterations in ESCC. These findings increase our understanding of therapeutic resistance and support the rationale for precision chemoradiotherapy.Significance:Whole-exome sequencing reveals the genetic evolution of ESCC during chemoradiotherapy, highlighting MYC gain in pretreatment tumors as a potential marker of therapy resistance.

Supplementary Figure S5 and legend

Supplementary Table S1

Supplementary Methods

Isotopomer distribution analysis using [U-13C]glucose in HuH7 cells with or without ectopic FBP1 expression.

Promoter methylation and copy number profiles of FBP1 in liver cancer cell lines from the Cancer Cell Line Encyclopedia.

Supplementary Materials and Methods, and Legends for Supplementary Figures.

Esophageal squamous cell carcinoma (ESCC) often recurs after chemoradiotherapy, and the prognosis of ESCC after chemoradiotherapy has not improved over the past few decades. The mutation process in chemoradiotherapy-resistant clones and the functional relevance of genetic alterations remain unclear. To address these problems, we performed whole-exome sequencing of 52 tumor samples from 33 patients with ESCC who received radiotherapy combined with 5-fluorouracil/platinum. In multiregion analyses of pretreatment and locally recurrent lesions from five cases, most driver gene-altered clones remained under chemoradiotherapy selection pressure, while few driver gene alterations were acquired at recurrence. The mutation signatures of recurrent ESCC, including increased deletion frequency and platinum dose-dependent base substitution signatures, were substantially different from those of primary ESCC and reflected the iatrogenic impacts of chemoradiotherapy. Single-region analysis of 28 pretreatment tumors indicated that focal copy-number gain at the MYC locus was significantly associated with poor progression-free survival and overall survival after chemoradiotherapy. MYC gain remained throughout the chemoradiotherapy course and potentially contributes to intrinsic resistance to chemoradiotherapy. Consistent with these findings, MYC copy number and mRNA and protein levels in ESCC cell lines correlated positively with resistance to radiotherapy, and MYC knockdown improved sensitivity to radiotherapy. Overall, these data characterize the clonal evolution process induced by chemoradiotherapy and clinically relevant associations for genetic alterations in ESCC. These findings increase our understanding of therapeutic resistance and support the rationale for precision chemoradiotherapy. Significance: Whole-exome sequencing reveals the genetic evolution of ESCC during chemoradiotherapy, highlighting MYC gain in pretreatment tumors as a potential marker of therapy resistance.

In response to the recommendation by the International Commission on Radiological Protection to lower the equivalent eye dose limit, the Japanese Government in April 2021 lowered the equivalent dose limit for the eye lens for occupational exposure. A considerable number of interventional radiology operators are exposed to levels above the new limit. For this reason, a need exists to more accurately evaluate eye lens dose in interventional radiology operators by using a novel direct eye dosimeter, the DOSIRIS™(IRSN, France), which is capable of measuring a 3-mm dose equivalent under protective glasses. The DOSIRIS is a thermoluminescent dosimeter that exhibits good energy dependence and better directional properties than other dosimeters. Dosimetry using DOSIRIS might be accurate and compatible with the latest regulations.

Background/aim The cytolytic activity (CYT) score is a new index of cancer immunity calculated from the mRNA expression levels of GZMA and PRF1. We assessed the clinical significance of the CYT score in HCC. Materials and methods The calculated CYT scores of peripheral blood cells (GSE24759), cell lines (CCLE) and HCC tissues (TCGA, GSE14520 and Kyushu cohorts) were assessed. Then, immunohistochemical analysis (IHC) of GZMA and PRF1 was performed. Results The CYT scores of HCC tissues were lower than those of non-cancerous tissues. The 5-year recurrence-free survival of patients with low CYT scores was significantly shorter than that of patients with high CYT scores. Multivariate analysis indicated that the CYT score was an independent prognostic factor for RFS in TCGA and GSE14520 cohorts. Conclusion CYT score could be a useful prognostic biomarker in HCC, possibly through reflecting the host immune status.

Purpose Most small renal cell carcinomas (small RCCs) will remain indolent after detection, but some stage I RCCs still metastasize. There are no risk-stratification imaging factors that could be used to identify poor-prognosis patients based on genomic profiling. Here, we evaluated the relationships between imaging parameters and RNA expressions in small RCC and attempted to identify imaging factors that could be used as effective biomarkers. Methods We acquired biopsy specimens of 18 clear cell carcinomas that had undergone perfusion CT (pCT) and MRI between April 2018 and March 2019. We performed RNA sequencing, assessed RNA expressions, and calculated each tumor’s cell-cycle progression (CCP) score, which has prognostic value in predicting metastatic progression. We classified the tumors into two groups: clear cell type A (ccA) and type B (ccB). CcA has better survival compared to ccB. We evaluated the following characteristics of each tumor: tumor size, presence of pseudocapsule, and fat. We used the pCT and MRI to measure each tumor’s volume transfer constant (Ktrans), rate constant (Kep), extracellular extravascular volume fraction (VE), fractional plasma volume (VP), and apparent diffusion coefficient (ADC). The correlations between these small RCC imaging parameters and the tumor size and RNA expressions were determined. Results The tumor size was significantly correlated with Kep and inversely correlated with VE, VP, ADC, and hallmark angiogenesis. The CCP score was significantly inversely correlated with Ktrans and Kep. The ccA tumors tended to show a pseudocapsule on MRI. Conclusion Tumor size was correlated with low perfusion, but not with prognostic factors based on genomic profiling. Imaging parameters (e.g., Ktrans and Kep) and tumor characteristics (e.g., pseudocapsule) may enable gene-based risk stratification in small RCC.

Mitochondria are important cellular organelles that function as control centers of the energy supply for highly proliferative cancer cells and regulate apoptosis after cancer chemotherapy. Cisplatin is one of the most important chemotherapeutic agents and a key drug in therapeutic regimens for a broad range of solid tumors. Cisplatin may directly interact with mitochondria, which can induce apoptosis. The direct interactions between cisplatin and mitochondria may account for our understanding of the clinical activity of cisplatin and development of resistance. However, the basis for the roles of mitochondria under treatment with chemotherapy is poorly understood. In this review, we present novel aspects regarding the unique characteristics of the mitochondrial genome in relation to the use of platinum-based chemotherapy and describe our recent work demonstrating the importance of the mitochondrial transcription factor A (mtTFA) expression in cancer cells.

Downregulation of paired related homeobox 1 (PRRX1) is associated with the acquisition of cancer stem cell (CSC)-like properties and poor prognosis in cancers. The purpose of this study is to clarify the role of PRRX1 expression in predicting prognosis and mediating CSC-like properties in hepatocellular carcinoma (HCC). The association between PRRX1 expression and overall survival (OS) of patients with HCC was analyzed in three independent datasets: 62 resected primary cases, 242 cases from GSE14520, and 162 cases from The Cancer Genome Atlas (TCGA). A cell line expressing PRRX1 (HuH7) was established for the functional analyses. The ability to form spheres, the expression levels of the hepatic CSC surface markers (CD13, CD133, and EpCAM), in vitro chemosensitivity to 5-fluorouracil (FU), and radiosensitivity were evaluated. Univariate and multivariate analyses showed that the 5-year OS of the low PRRX1 expression group was significantly poorer than that of the high PRRX1 expression group (P = 0.024 and P = 0.045, respectively). Consistent with this, the low PRRX1 expression group in GSE14520 and TCGA datasets showed significantly shorter OS (P = 0.027 and P = 0.010, respectively). Gene set enrichment analysis on GSE14520 and TCGA datasets indicated that downregulation of PRRX1 was correlated with the stemness signature. The number of spheres and the expression levels of CSC markers were significantly decreased when PRRX1 was expressed. Moreover, PRRX1 impaired resistance to 5-FU and radiation. Downregulation of PRRX1 expression contributes to the poor prognosis of patients with HCC through acquisition of CSC-like properties.

Recently, image-guided radiotherapy (IGRT) systems using kilovolt cone-beam computed tomography (kV-CBCT) images have become more common for highly accurate patient positioning in stereotactic lung body radiotherapy (SLBRT). However, current IGRT procedures are based on bone structures and subjective correction. Therefore, the aim of this study was to evaluate the proposed framework for automated estimation of lung tumor locations in kV-CBCT images for tumor-based patient positioning in SLBRT. Twenty clinical cases are considered, involving solid, pure ground-glass opacity (GGO), mixed GGO, solitary, and non-solitary tumor types. The proposed framework consists of four steps: (1) determination of a search region for tumor location detection in a kV-CBCT image; (2) extraction of a tumor template from a planning CT image; (3) preprocessing for tumor region enhancement (edge and tumor enhancement using a Sobel filter and a blob structure enhancement (BSE) filter, respectively); and (4) tumor location estimation based on a template-matching technique. The location errors in the original, edge-, and tumor-enhanced images were found to be 1.2 ± 0.7 mm, 4.2 ± 8.0 mm, and 2.7 ± 4.6 mm, respectively. The location errors in the original images of solid, pure GGO, mixed GGO, solitary, and non-solitary types of tumors were 1.2 ± 0.7 mm, 1.3 ± 0.9 mm, 0.4 ± 0.6 mm, 1.1 ± 0.8 mm and 1.0 ± 0.7 mm, respectively. These results suggest that the proposed framework is robust as regards automatic estimation of several types of tumor locations in kV-CBCT images for tumor-based patient positioning in SLBRT.

Introduction The relationship between the washout pattern and constituent cell in adrenal hyperplasia (AH) has not been fully investigated. The purpose of this study was to elucidate the radiological or pathological factors determining the washout pattern of AH on dynamic CT. Methods Ten patients with 14 surgically proven AHs were enrolled. Dynamic CT was scanned before (pre-contrast image) and 60 seconds (early phase) and 240 seconds (delayed phase) after administration of iodine contrast. The absolute percentage washout (APW) of each nodular lesion was calculated using the following formula: APW(%) = (TAearly-TAdelay)/(TAearly-TApre) × 100, when TApre, TAearly and TAdelay were defined as tumour attenuation values of pre-contrast, early and delayed phases, respectively. Pathologically, the clear cell ratio (CCR) constituting each nodular lesion was qualitatively assessed. Regression analysis was performed to evaluate a correlation between each pair of CCR, TApre, (TAearly-TAdelay) and APW. Results There was a significant correlation between each pair of CCR, TApre and APW. CCR decreased as TApre increased (r = 0.81, P

Plexiform fibromyxoma is a relatively new pathological category that consists of a rare group of non-gastrointestinal stromal tumors with a peculiar plexiform growth pattern. We report a case of gastric plexiform fibromyxoma in a 60-year-old man. Gastroscopic examination revealed a gastric submucosal tumor in the antrum. Magnetic resonance imaging (MRI) showed a nodule with distinct signal hyperintensity on T2-weighted images, with strong enhancement peripherally in the early phase to the entire lesion in the delayed phase. Endoscopic ultrasound-guided fine-needle aspiration cytology was performed, and the cytological diagnosis was spindle cell tumor, so partial gastrectomy was performed under a preoperative diagnosis of GIST. The resected tumor demonstrated plexiform architecture, myxoid stroma, prominent vasculature, and spindle cells, reflecting the characteristic findings on MRI. This is the first report to describe radiological findings for gastric plexiform fibromyxoma.

Background and Aim A faint hypointensity in the noncancerous tissue around hepatocellular carcinoma (HCC) in the hepatobiliary phase of Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) is encountered. The goal is to elucidate the significance of this type of pseudolesion designated as the peritumoral decreased uptake area of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) (PDUAE). Methods This study group consisted of 61 patients with 61 surgically resected HCCs who underwent preoperative Gd-EOB-DTPA-enhanced MRI. The presence of a faint and hypointense area around the tumor in the hepatobiliary phase was defined as PDUAE. The frequency with which PDUAE was seen was compared between pairs of groups determined by clinical and pathological parameters using a Fisher's exact probability test. The parameters showing significant differences in this test were further tested by multiple logistic regression analysis. Results PDUAE was observed in 25 cases. In univariate analysis, the values of alpha-fetoprotein and protein-induced by vitamin K absence or antagonist-II, maximal diameter, the presence of a capsule, and vascular invasion were significantly correlated with the frequency with which PDUAE was seen. In multivariate analysis, only maximal diameter and vascular invasion were significantly correlated. When the presence of PDUAE was used as an indicator of vascular invasion, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 72%, 80.6%, 77%, 72%, and 80.6%, respectively. Conclusions By using this indicator, “microscopic” vascular invasion of HCC can be easily predicted with Gd-EOB-DTPA-enhanced MRI.

Background: Pancreatic cancer (PC) is the most lethal cancer in humans, with a 5-year survival rate of less than 10%. Thus, identification of prognostic biomarkers as well as molecular therapeutic targets should be critical. Translational reprogramming in cancer has been attracting attention. Several studies have reported that genomic alternations of a translational regulatory gene contributing to malignancy. eIF5-mimic protein 1 (5MP1), previously termed BZW2 is a member of the bZIP superfamily of transcription factors. 5MP1 is reported to be upregulated and has a pro-tumor effect via activation of the Akt/mTOR signaling pathway in osteosarcoma. However, the role and mechanisms of 5MP1 in PC remains unknown. The aim of this study is to clarify the clinical significance of 5MP1 expression in PC. Material and method: Firstly, we analyzed public datasets of PC (178 RNA-sequencing data from The Cancer Genome Atlas, 36 gene expression array data from GSE 15471, 45 gene expression array data from GSE 28735, 69 gene expression array data from GSE 62452, 145 primary PC and 46 normal pancreas gene expression array data from GSE 71729, 45 Copy number variation and expression array data from Broad-Novartis Cancer Cell Line Encyclopedia(CCLE)). Then we performed Gene set enrichment analysis (GSEA) to identify the gene sets which were associated with the expression of 5MP1 in PC. Finally, we investigated the localization of 5MP1 by immunohistochemical staining data of THE HUMAN PROTEIN ATLAS and also confirmed with staining our histological specimens. Results: In tumor tissues, mRNA expression of 5MP1 was higher than normal tissues (t-test. p Conclusion and Significance: We demonstrated that 5MP1 was overexpressed in PC cells, and the high expression was associated with poor prognosis. These results suggest that 5MP1 may be associated with tumor progression and can be a promising biomarker for a patient with a poor prognosis of PC. Now we are performing a knockdown experiment for 5MP1 to clarify its biological significance in PC. Citation Format: Yushi Motomura, Takaaki Masuda, Kuniaki Sato, Atsushi Fujii, Akihiro Kitagawa, Hiroaki Wakiyama, Kensuke Koike, Junichi Takahashi, Dai Shimizu, Shotaro Kuramitsu, Miwa Noda, Yusuke Tsuruda, Hajime Otsu, Yosuke Kuroda, Hidetoshi Eguchi, Katsumi Sakamoto, Masakazu Hirakawa, Hiroshi Honda, Koshi Mimori. Clinical significance of eif5-mimic protein 1 in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 475.

The purpose of this study is to evaluate the real-time respiratory motion of the prostate and surrounding tissues/organs in the supine and prone positions and to investigate, using cine-MRI, whether a belly board can reduce respiratory-induced motion in the prone position. Cine-MRI scans were made of 13 volunteers in the supine and prone positions on a flat board and in two different prone positions using a belly board. Images in cine mode were recorded for 20 seconds. For each session, the points of interest (POIs) were located at the apex, base, mid-anterior surface and mid-posterior surface of the prostate; the tip of the seminal vesicle; the pubic symphysis; and the sacrum. The maximum range and standard deviation (SD) of the displacement from the mean value were calculated. The SDs for each of the four different positions were compared using a paired t-test. Respiratory-induced prostate motion was significantly larger in the prone position than in the supine position. However, when a belly board was used in the prone position, motion in the prostate and surrounding tissues/organs was significantly reduced. There were no significant differences between the two different positions using a belly board in any of the POIs.

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).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.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 (P0.05). 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 (P0.05).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.

We designed a phase I trial to investigate the safety, immune responses and clinical benefits of a five-peptide cancer vaccine in combination with chemotherapy. Study subjects were patients positive for HLA-A2402 with locally advanced, metastatic, and/or recurrent gastrointestinal, lung or cervical cancer. Eighteen patients including nine cases of colorectal cancer were treated with escalating doses of cyclophosphamide 4days before vaccination. Five HLA-A2402-restricted, tumor-associated antigen (TAA) epitope peptides from KOC1, TTK, URLC10, DEPDC1 and MPHOSPH1 were injected weekly for 4weeks. Treatment was well tolerated without any adverse events above grade 3. Analysis of peripheral blood lymphocytes showed that the number of regulatory T cells dropped from baseline after administration of cyclophosphamide and confirmed that TAA-specific T cell responses were associated significantly with longer overall survival. This phase I clinical trial demonstrated safety and promising immune responses that correlated with vaccine-induced T-cell responses. Therefore, this approach warrants further clinical studies.

The telomere length of somatic cells shortens with age and with other endogenous and exogenous pathogenic factors. However, the effects of radiation therapy on telomere DNA of non-cancer tissue have not been thoroughly investigated. This study analyzed the telomere length of inpatients with cancer treated with radiation therapy to see whether the telomere lengths change in response to therapeutic radiation.Twenty-five patients were enrolled in the study. The patients had lung cancer, prostate cancer, thyroid cancer, hepatoma, or rectal cancer. They received radiation therapy with a dose range of 15-74 Gy. The telomere lengths and telomere length distribution in peripheral leukocytes were analyzed by using a Southern blot-based method.The telomere length and the telomere length distribution of the peripheral leukocytes did not change after radiation therapy. However, there was a significant proportional decrease in the short telomere fraction (4.4 kb) per day and per Gy.This observation suggested that the telomere length distribution of peripheral leukocytes could be affected by radiation therapy, and that the effect of radiation tends to appear in cells with short telomeres. Radiation therapy-associated somatic telomere length change within a short range of time, about three months or shorter, can be detected by analyzing the mean telomere length and telomere length distribution.

We evaluated the relationships between pre-procedural radiological findings and short-term pain relief in patients with osteoporotic compression fractures after percutaneous vertebroplasty (PVP). A retrospective review of pre-procedural radiological images of 156 patients with painful osteoporotic compression fracture was performed. Pain was measured with a visual analogue scale (VAS). Complete pain relief was defined as a VAS pain score of 0 or 1 at 3 months after PVP. Statistical analyses were conducted to evaluate the relationship between the pre-procedural imaging factors and pain relief using Pearson’s chi-squared test. Multivariate logistic regression analysis was also performed. Complete pain relief was obtained in 45.5% of patients. An intravertebral cleft larger than half the height of the fractured vertebral body (FVB) was a significant key factor in the complete pain relief group after 3 months. Further, ≥40% of the spinal canal occupied by bony fragments of the FVB was related to incomplete pain relief. A large intravertebral cleft was a favorable short-term outcome predictor in patients with osteoporotic compression fractures after PVP, while severe protrusion of the FVB causing lumbar spinal canal stenosis was not a favorable short-term outcome predictor of complete pain relief.

SUMMARY Nonerosive reflux disease (NERD) is classified into grade M (minimal change, endoscopically; erythema without sharp demarcation, whitish turbidity, and/or invisibility of vessels due to these findings) and grade N (normal) in the modified Los Angeles classification system in Japan. However, the classification of grades M and N NERD is not included in the original Los Angeles system because interobserver agreement for the conventional endoscopic diagnosis of grades M or N NERD is poor. Flexible spectral imaging color enhancement (FICE) is a virtual chromoendoscopy technique that enhances mucosal and vascular visibility. The aim of this study is to evaluate whether the endoscopic diagnosis of grades M or N NERD using FICE images is feasible. Between April 2006 and May 2008, 26 NERD patients and 31 controls were enrolled in the present study. First, an experienced endoscopist assessed the color pattern of minimal change in FICE images using conventional endoscopic images and FICE images side-by-side and comparing the proportion of minimal change between the two groups. Second, three blinded endoscopists assessed the presence or absence of minimal change in both groups using conventional endoscopic images and FICE images separately. Intraobserver variability was compared using McNemar's test, and interobserver agreement was described using the kappa value. Minimal changes, such as erythema and whitish turbidity, which were detected using conventional endoscopic images, showed up as navy blue and pink-white, respectively, in color using FICE images in the present FICE mode. The NERD group had a higher proportion of minimal change, compared with the control group (77% and 48%, respectively) (P= 0.033). In all three readers, the detection rates of minimal change using FICE images were greater than those using conventional endoscopic images (P= 0.025

The aim of this study was to elucidate computed tomography hepatic arteriography (CTHA) and CT arterial portography (CTAP) findings characteristic of hepatocellular carcinoma (HCC) with large hepatic venous invasion (HVI) and then to examine whether the presence of minute HVI can be diagnosed based on each finding.Combined CTHA and CTAP of 106 HCCs were examined. Two radiologists analyzed the radiological findings of five nodules with large HVI (group vv2). The remaining 101 nodules were classified into two groups: group vv1, positive minute HVI; group vv0, negative HVI. They examined whether each finding observed in group vv2 could be detected in groups vv1 and vv0.Analysis of group vv2 identified (a) tumor thrombus, (b) early inflow of the contrast into the hepatic vein proximal to the invaded site, and (c) partially decreased portal venous flow in the peripheral parenchyma subject to the involved hepatic vein. Findings (b) and (c) were observed in 16% of group vv1. A significant difference in frequency of finding (c) was obtained between groups vv1 and vv0. The positive and negative predictive values of finding (c) were 66.7% and 77.9%, respectively.Findings (b) and (c), especially the latter, may partly contribute to the radiological diagnosis of minute HVI.

Purpose: To evaluate whether diffusion-weighted imaging (DWI) improves the detection of hepatocellular carcinoma (HCC) on super paramagnetic iron oxide (SPIO)-enhanced MRI. Materials and Methods: This retrospective study group consisted of 30 patients with 50 HCC nodules who underwent MRI at 1.5 Tesla. Two combined MR sequence sets were compared for detecting HCC: SPIO-enhanced MRI (axial T2-weighted fast spin-echo (FSE) and T1-/T2*-weighted fast field echo (FFE) scanned before and after administration of ferucarbotran) and SPIO-enhanced MRI + DWI (SPIO-enhanced MRI with axial DWI scanned before and after administration of ferucarbotran). Three blinded readers independently reviewed for the presence of HCC on a segment-by-segment basis using a four-point confidence scale. The performance of the two combined MR sequence sets was evaluated using receiver operating characteristic (ROC) analysis. Results: The average area under the ROC curve (Az) of the three readers for the SPIO-enhanced MRI + DWI set (0.870 ± 0.046) was significantly higher that that for the SPIO-enhanced MRI set (0.820 ± 0.055) (P = .025). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for detection of HCC were 66.0%, 98.0%, 90.0%, and 91.4%, respectively, for the SPIO-enhanced MRI set, and 70.0%, 98.6%, 92.9%, and 92.4%, respectively, for the SPIO-enhanced MRI + DWI set. Conclusion: The SPIO-enhanced MRI + DWI set outperformed the SPIO-enhanced MRI set for depicting HCC. J. Magn. Reson. Imaging 2010; 31: 373–382. © 2010 Wiley-Liss, Inc.

Purpose To investigate the validity of the fetal right lung-to-liver signal intensity ratio (LLSIR) for prediction of postnatal outcomes in left-sided congenital diaphragmatic hernia (CDH) Materials and Methods The study included 14 pregnant women who underwent MR exams for evaluation of fetal left-sided CDH. The fetuses were divided into two groups: Group A (n = 9), alive, and Group B (n = 5), dead. On the basis of the half-Fourier acquisition single-shot turbo spin-echo sequence, LLSIR and the right fetal lung volume (FLV) was calculated. In the control group, a regression analysis was performed to associate LLSIR and right FLV with gestational age. The relative LLSIR and right FLV (the observed/expected LLSIR and right FLV) were compared between Groups A and B. Results The mean relative LLSIR, as well as the mean relative right FLV, of Group A was significantly higher than that of Group B (p = 0.035). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for the relative LLSIR and the relative right FLV, when the cutoff point was defined as 0.646 and 0.420, were the same and were 88.9%, 80.0%, 88.9%, 80.0%, and 85.7%, respectively. Conclusion The postnatal outcomes in left-sided CDH may be predicted using the LLSIR. J. Magn. Reson. Imaging 2009;30:112–120. © 2009 Wiley-Liss, Inc.

To assess the value of the delayed phase (DP) in pancreatic carcinomas which appear iso-attenuating in the pancreatic parenchymal phase (PPP).Fifty-seven preoperative MDCT studies of pancreatic carcinomas were retrospectively reviewed. The size of the tumors, and the Hounsfield unit (HU) of the tumors and pancreatic parenchyma were measured. The tumor-to-pancreas contrast (TPC: |HU [tumor]-HU [normal pancreas]|) was calculated.Eight cases (14.0%) showed iso-attenuation and 49 showed hypo-attenuation in the PPP. The DP images revealed seven of eight (87.5%) iso-attenuating tumors to be hyper-attenuating. The size of iso-attenuating tumors was smaller than that of hypo-attenuating tumors (mean+/-S.D.: 12.4+/-4.8mm vs. 30.3+/-9.0mm, p0.0001). In hypo-attenuating tumors, TPC in the PPP (60.2+/-24.6 HU) was higher than those in the portal venous phase (PVP, 40.5+/-23.0 HU, p0.0001) and DP (18.3+/-11.8 HU, p0.0001). In contrast, in iso-attenuating tumors, TPC in the DP (26.0+/-4.9 HU) was higher than those in the PPP (9.2+/-3.7 HU, p=0.0003) and PVP (7.1+/-4.7 HU, p=0.001) phases.The DP image is helpful in depicting small iso-attenuating pancreatic carcinomas as slightly hyper-attenuating tumors.

The purpose of this pictorial essay was to aid in the understanding of the anatomy of the iliopsoas groove by presenting imaging of various lesions affecting this region. Neurogenic tumors, lymphangiomas, lymphangioleiomyomatosis, and posterior iliac crest lymph node metastases may present as masses in the iliopsoas groove. Iliopsoas abscess secondary to infections of the adjacent structures, tumors of the iliopsoas muscle, and iliopsoas hematomas may directly extend to this region.

Osteoid osteoma is a benign bone tumor traditionally treated nonoperatively or by operative excision. However, radiofrequency ablation (RFA) is being used increasingly for treatment of osteoid osteoma, as there are several reports supporting its effectiveness. We present a case of osteoid osteoma of femur in an 18-year-old boy. The patient complained of pain in right hip and knee joint. The osteoid osteoma lesion was successfully treated by percutaneous computed tomography (CT)-guided RFA using the cool-tip RFA system under general anesthesia. He had total pain relief within 24 hours following the procedure. No complications were recorded. He discharged on foot two days after RFA therapy. Complete regression of symptoms was observed at 2-year follow-up. CT-guided RFA for osteoid osteoma is a safe, effective and minimally invasive procedure with high success rate and lack of relapse.

To compare plain computed tomography (CT) and chemical-shift MR imaging (CSI) for establishing a noninvasive method to estimate the degree of steatosis.A total of 58 patients who had histological proof of liver tissue and underwent CT and/or CSI within two weeks, were studied. They consisted of 38 living donor candidates and 20 liver surgery patients without hepatitis or cirrhosis. The CT index (CTI) and MR index (MRI) were defined and correlated to histological grades of steatosis. Correlation was also performed exclusively for mild steatosis (grades 0-2).Both plain CT (rho=0.74, P0.0001) and CSI (rho=0.83, P0.0001) had good correlation with histological grades of steatosis, showing no significant difference between them. For mild steatosis, CSI (rho=0.77, P0.0001) had better correlation than CT (rho=0.49, P=0.001) (P=0.049). Accuracy in differentiation between grade 0-1 vs. grade 2-4 steatosis was 85% using a CTI6, and 91% using an MRI0.03 as criteria. That between grade 0-2 and grade 3-4 was 91% using a CTI-8 and 88% using an MRI0.25 as criteria.Both plain CT and CSI were useful in estimating the degree of steatosis but CSI was superior to CT in differentiating mild steatosis. These indices may at least partially replace percutaneous biopsy in evaluating grades of steatosis for living donors.

To evaluate the interval change of perivascular soft tissue (PVST) around the common hepatic and proximal superior mesenteric arteries arising after pancreaticoduodenectomy (PD) and to compare the difference between post operative change (benign PVST) and recurrence (malignant PVST). Serial multidetector CT (MDCT) studies in 44 patients who underwent PD for periampullary carcinomas were retrospectively reviewed (Group A). The incidence and interval change of PVST were evaluated and compared to control group (Group B, 21 patients with PD for benign diseases). PVST was seen in all the 44 patients in Group A, and it was noted in 12 of 21 (57.1%) patients in Group B. Thirteen of 44 (29.5%) patients showed interval enlargement of PVST (malignant PVST), and 12 of 13 developed within 2 years after PD. There was higher incidence of malignant PVST in patients with lymph node metastasis (p

Hepatic surface enhancement on CT can represent particular clinical significance in various abdominal conditions, at times being the only abnormality found. Detecting hepatic surface enhancement, together with the other ancillary diagnostic techniques as well, may lead to grasp of the underlying condition and to early or timely diagnosis and treatment of abdominal disorders. This manuscript describes the spectrum of hepatic surface enhancement on CT, and the importance of focusing on the hepatic surface during interpretation is emphasized.

Purpose To evaluate the diagnostic efficacy of curved planar reformations along the duct (long-axis CPR) and series of reformations perpendicular to the duct (short-axis MPR) in evaluating T-factors of pancreaticobiliary malignancy. Materials and methods Twenty-five patients with surgically proven pancreaticobiliary malignancy (12 bile duct cancers and 13 pancreas cancers) were evaluated. A dynamic study was performed with multidetector-row CT with four detectors, and reconstructed with 1 mm thickness and intervals. Tracing the center of the duct system on axial images, long-axis CPR images and serial short-axis MPR images were obtained. Two radiologists interpreted the T factor of the diseases three times: session (1), axial images only; session (2), axial, coronal and sagittal multiplanar reformation images; and session (3), axial, long-axis CPR, and short-axis MPR images. Receiver operating characteristic curves were analyzed. Results In evaluations of bile duct cancer, Az values of (3) (0.95, 0.92) were higher than those of (1) (0.89, 0.88) and (2) (0.92, 0.89), with some significant differences. In evaluations of pancreas cancer, Az values of all interpretations were almost equal. Conclusion Long-axis CPR and short-axis MPR images were suggested to be useful as additional images to the original axial images in evaluating the local extension of bile duct carcinomas.

OBJECTIVE. The purpose of our study was to evaluate the detectability of the gonadal vein of transposed ovaries in patients with uterine cervical cancer on MDCT.CONCLUSION. Gonadal veins and surgical clips of transposed ovaries can be shown with high consistency on MDCT. Tracking the gonadal veins and detecting the surgical clips may prevent the transposed ovaries from being misinterpreted as peritoneal implants.

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.

The objective of our study was to evaluate the diagnostic accuracy of MDCT and conventional angiography in the detection of an accessory left gastric artery using CT hepatic arteriography as the standard of reference.The study group consisted of 118 patients who underwent MDCT with a triple-phase liver protocol with a slice thickness of 5 mm, conventional angiography, and CT hepatic arteriography. The early-phase images of MDCT and conventional angiography were retrospectively reviewed. The presence or absence of an accessory left gastric artery was evaluated using CT hepatic arteriography as the standard of reference. The sensitivity, specificity, and accuracy of MDCT and conventional angiography were calculated.CT hepatic arteriography revealed an accessory left gastric artery in 25 (21.2%) of 118 cases, including 15 proximal- and 10 distal-type accessory left gastric arteries. On MDCT, there were seven false-negative cases and one false-positive case. Six of the seven false-negative cases were a proximal-type accessory left gastric artery, and nine of 10 distal-type accessory left gastric arteries were correctly diagnosed using MDCT. The sensitivity, specificity, and accuracy of MDCT were 72.0%, 98.9%, and 93.2%, respectively. On conventional angiography, there were three false-negative and two false-positive cases, none of whom underwent selective left hepatic arteriography. Two of the three false-negative cases were the distal-type accessory left gastric artery, but eight of the 10 distal-type accessory left gastric arteries were correctly diagnosed. The sensitivity, specificity, and accuracy of conventional angiography were 88.0%, 97.8%, and 95.8%, respectively.Approximately 70% of accessory left gastric arteries can be diagnosed at the early phase of MDCT even with a slice thickness of 5 mm.

We have previously reported that both hypotonic stress (HTS) and lysophosphatidic acid (LPA) induce ATP release and a transient reorganization of actin through sequential activation of RhoA/Rho-kinase and focal adhesion kinase F-actin (FAK)/paxillin in human umbilical cord vein endothelial cells (HUVECs). LPA is known to induce the activation of RhoA via its specific receptors, but the mechanisms by which HTS initiates these intracellular signals are not known. The present study aimed to identify the molecule(s) that are unique to the sensing and/or transducing the mechanical stress. Reverse transcriptase-polymerase chain reaction revealed the expression of several integrin subunits in HUVECs. Anti-integrin α5β1 antibody (Ab), but not anti-integrin α2, α6, αv, or β4 antibodies, inhibited HTS-induced RhoA translocation, tyrosine phosphorylation of FAK and paxillin, ATP release, and actin reorganization. However, the LPA-induced ATP release and actin reorganization were not inhibited by any of these anti-in...