Publications by authors named "Takeshi Yokoo"

97 Publications

Abbreviated magnetic resonance imaging vs ultrasound for surveillance of hepatocellular carcinoma in high-risk patients.

Liver Int 2021 Nov 24. Epub 2021 Nov 24.

Liver Cancer Center, Asan Medical Center, Seoul, Republic of Korea.

Background & Aims: We aimed to compare the performance of gadoxetic acid-enhanced abbreviated MRI (AMRI)-based surveillance and ultrasound-only surveillance in high-risk patients for hepatocellular carcinoma (HCC).

Methods: Prospectively recruited high-risk patients (>5% annual risk of HCC) who underwent one to three rounds of complete gadoxetic acid-enhanced MRI (CMRI) and ultrasound at 6-months intervals were retrospectively analysed. AMRI consisted of diffusion-weighted, T2-weighted, and hepatobiliary phase imaging. The sensitivity, specificity, and accuracy of CMRI followed by AMRI (CAA), AMRI-only (AAA), and ultrasound-only (US) were compared using generalized estimating equations. Image quality was assessed.

Results: In 382 patients, HCC was diagnosed in 43 (11.3%), including 42 with early-stage HCCs. The sensitivities of CAA (90.7%, 39/43) and AAA (86.0%, 37/43) were higher than US (27.9% [12/43]; P < 0.001), whereas the sensitivities of the two MRI approaches did not significantly differ (P = 0.56). The specificity of CAA (97.1%, 983/1012) was higher than AAA (95.6% [967/1012]; P = 0.01) and not significantly different from US (96.3% [975/1012]; P = 0.59). The CAA approach had the best accuracy of 96.9% (1022/1055), higher than the AAA approach (95.2% [1004/1055]; P = 0.01) and the US approach (93.6% [987/1055]; P = 0.01). Image quality was inadequate in 33.7% (356/1055) of US examinations but in only 10.0% (105/1055) of the AAA and 11.1% (117/1055) of the CAA approach.

Conclusions: In high-risk patients, AMRI-based surveillance approaches had higher sensitivities than ultrasound-only surveillance for early-stage HCC. A sequential MRI approach of CMRI followed by AMRIs showed superior accuracy than the AMRI-only or ultrasound-only approach.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/liv.15110DOI Listing
November 2021

CT/MRI and CEUS LI-RADS Major Features Association with Hepatocellular Carcinoma: Individual Patient Data Meta-Analysis.

Radiology 2021 Nov 16:211244. Epub 2021 Nov 16.

From the Dept of Diagnostic Imaging, Juravinski Hosp and Cancer Centre, Hamilton Health Sciences, McMaster Univ, Hamilton, Canada (C.B.v.d.P.); Dept of Radiology and Epidemiology, Univ of Ottawa, Ottawa, Canada (M.D.F.M.); Ottawa Hosp Research Inst Clinical Epidemiology Program, Dept of Medical Imaging, the Ottawa Hosp-Civic Campus, 1053 Carling Ave, Room c-159, Ottawa, ON, Canada K1E 4Y9 (M.D.F.M.); Faculty of Health Sciences, Queen's Univ, Kingston, Canada (J.P.S.); Clinical Epidemiology Program, Ottawa Hosp Research Inst, Ottawa, Canada (J.P.S.); Centre for Prognosis Research, School of Medicine, Keele Univ, Staffordshire, UK (B.L.); Dept of Radiology, Montefiore Medical Ctr, Bronx, NY (V.C.); Liver Imaging Group, Dept of Radiology, Univ of California San Diego, San Diego, Calif (C.B.S.); Depts of Radiology (M.R.B., B.C.A.) and Medicine (M.R.B.) and Ctr for Advanced Magnetic Resonance Development (M.R.B.), Duke Univ Medical Ctr, Durham, NC; Dept of Radiology, Univ of North Carolina, Chapel Hill, NC (M.R.B., L.M.B.B., K.A.M.); Dept of Radiology, Research Inst of Radiological Science, Yonsei Univ College of Medicine, Seoul, Korea (J.Y.C., M.J.K., Y.Y.K., M.S.P.); Asan Medical Ctr, Univ of Ulsan College of Medicine, Seoul, Korea (S.H.C.); BCLC Group, Liver Unit, Hosp Clínic of Barcelona, Barcelona, Spain (A.F.); IDIBAPS, CIBERehd, Univ of Barcelona, Barcelona, Spain (A.F.); Mallinckrodt Inst of Radiology, Washington Univ School of Medicine, St Louis, Mo (T.J.F.); Div of Internal Medicine, Hepatobiliary and Immunoallergic Diseases (A.G., F.P., E.T.), and Emergency Dept, Medicina d'Urgenza e Pronto Soccorso (L.M.), IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Dept of Radiology, West China Hosp, Sichuan Univ, Chengdu, China (H.J.); Dept of Radiology (I.J., H.J.K., J.H.K., J.M.L.) and Inst of Radiation Medicine (J.H.K., J.M.L.), Seoul National Univ Hosp, Seoul, Korea; Dept of Radiology, Seoul National Univ College of Medicine, Seoul, Korea (I.J., J.H.K., J.M.L.); Dept of Radiology, Tongji Hosp, Tongji Medical College, Wuhan, China (Z.K.); Huazhong Univ of Science and Technology, Wuhan, China (Z.K.); Dept of Radiology, Weill Cornell Medical Ctr, New York, NY (A.S.K.); Dept of Radiology (G.K., T.Y.) and Advanced Imaging Research Ctr (T.Y.), Univ of Texas Southwestern Medical Ctr, Dallas, Tex; Dept of Radiology and Research Inst of Radiology, Univ of Ulsan College of Medicine, Asan Medical Ctr, Seoul, Korea (S.Y.K.); Dept of Radiology, Dong-A Univ Hosp, Dong-A Univ College of Medicine, Busan, Korea (H.K.); Dept of Radiology, Icahn School of Medicine at Mount Sinai, New York, NY (S.C.L.); 2nd Radiology Dept, Warsaw Medical Univ, Warsaw, Poland (J.P., G.R.); Inst of Diagnostic and Interventional Radiology, Univ Hosp Zurich, Zurich, Switzerland (C.S.R.); Dept of Radiology, Beaujon Hosp, APHP.Nord, Clichy, France (M.R.); Université de Paris, Paris, France (M.R.); Dept of Radiology, West China Hosp, Sichuan Univ, Chengdu, China (B.S.); Dept of Radiology, Jeonbuk National Univ Medical School and Hosp, Jeonju, Korea (J.S.S.); Dept of Radiology, Centre Hospitalier de l'Université de Montréal, Montréal, Canada (A.T.); Dept of Radiology, the Third Affiliated Hosp, Sun Yat-sen Univ, Guangzhou, China (J.W.); Dept of Medical Ultrasonics, Inst of Diagnostic and Interventional Ultrasound, the First Affiliated Hosp of Sun Yat-Sen Univ, Guangzhou, China (W.W.); Depts of Radiology and Medicine, Div of Gastroenterology, Univ of Calgary, Calgary, Canada (S.R.W.); and Foothills Medical Centre, Calgary, Canada (S.R.W.).

Background The Liver Imaging Reporting and Data System (LI-RADS) assigns a risk category for hepatocellular carcinoma (HCC) to imaging observations. Establishing the contributions of major features can inform the diagnostic algorithm. Purpose To perform a systematic review and individual patient data meta-analysis to establish the probability of HCC for each LI-RADS major feature using CT/MRI and contrast-enhanced US (CEUS) LI-RADS in patients at high risk for HCC. Materials and Methods Multiple databases (MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Scopus) were searched for studies from January 2014 to September 2019 that evaluated the accuracy of CT, MRI, and CEUS for HCC detection using LI-RADS (CT/MRI LI-RADS, versions 2014, 2017, and 2018; CEUS LI-RADS, versions 2016 and 2017). Data were centralized. Clustering was addressed at the study and patient levels using mixed models. Adjusted odds ratios (ORs) with 95% CIs were determined for each major feature using multivariable stepwise logistic regression. Risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) (PROSPERO protocol: CRD42020164486). Results A total of 32 studies were included, with 1170 CT observations, 3341 MRI observations, and 853 CEUS observations. At multivariable analysis of CT/MRI LI-RADS, all major features were associated with HCC, except threshold growth (OR, 1.6; 95% CI: 0.7, 3.6; = .07). Nonperipheral washout (OR, 13.2; 95% CI: 9.0, 19.2; = .01) and nonrim arterial phase hyperenhancement (APHE) (OR, 10.3; 95% CI: 6.7, 15.6; = .01) had stronger associations with HCC than enhancing capsule (OR, 2.4; 95% CI: 1.7, 3.5; = .03). On CEUS images, APHE (OR, 7.3; 95% CI: 4.6, 11.5; = .01), late and mild washout (OR, 4.1; 95% CI: 2.6, 6.6; = .01), and size of at least 20 mm (OR, 1.6; 95% CI: 1.04, 2.5; = .04) were associated with HCC. Twenty-five studies (78%) had high risk of bias due to reporting ambiguity or study design flaws. Conclusion Most Liver Imaging Reporting and Data System major features had different independent associations with hepatocellular carcinoma; for CT/MRI, arterial phase hyperenhancement and washout had the strongest associations, whereas threshold growth had no association. © RSNA, 2021
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1148/radiol.2021211244DOI Listing
November 2021

The prognosis and incidence of hepatic encephalopathy of patients with liver cirrhosis treated with proton pump inhibitors: A multicenter retrospective study in Japan.

Medicine (Baltimore) 2021 Aug;100(32):e26902

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan.

Abstract: Gastrointestinal bleeding, hepatic encephalopathy (HE), and hepatocarcinogenesis are associated with the prognosis of patients with liver cirrhosis (LC). Proton pump inhibitors (PPIs) have been used to prevent bleeding, however the effects of PPIs on overall survival have not yet been elucidated. Therefore, this multicenter retrospective study aimed to assess the effect of PPI on the prognosis and HE occurrence of the patients with liver cirrhosis in Japan.A total of 456 patients diagnosed with LC at the 4 institutes during the study period (2010-2014) were assessed. PPI-treated and non-treated patients were compared using propensity score matching analysis. Primary and secondary endpoints of the study were set as the occurrence of HE and overall survival, respectively.A comparison of all cases showed a significantly poorer hepatic reserve function in the PPI-treated patients. The propensity-score matching analysis was performed and 120 PPI-treated patients were 1:1 matched with non-treated patients. The analysis revealed a higher incidence of HE in the PPI-treated than in the non-treated patients (P = .032; hazard ratio [HR], 2.162; 95% confidence interval [CI], 1.066-4.176), but the prognosis of PPI-treated patients was no worse than that of non-treated patients (P = .676; HR, 1.101; 95% CI, 0.702-1.726).This retrospective study showed that PPI administration for the patients with liver cirrhosis may partly be related to the increased incidence of HE but not worsen the patient prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000026902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8360404PMC
August 2021

A blood-based prognostic liver secretome signature and long-term hepatocellular carcinoma risk in advanced liver fibrosis.

Med (N Y) 2021 Jul 21;2(7):836-850.e10. Epub 2021 Apr 21.

Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, U.S.

Background: Accurate non-invasive prediction of long-term hepatocellular carcinoma (HCC) risk in advanced liver fibrosis is urgently needed for cost-effective HCC screening; however, this currently remains an unmet need.

Methods: A serum-protein-based prognostic liver secretome signature (PLSec) was bioinformatically derived from previously validated hepatic transcriptome signatures and optimized in 79 patients with advanced liver fibrosis. We independently validated PLSec for HCC risk in 331 cirrhosis patients with mixed etiologies (validation set 1 [V1]) and thereafter developed a score with clinical prognostic variables. The score was then validated in two independent cohorts: validation set 2 (V2): 164 patients with advanced liver fibrosis due to hepatitis C virus (HCV) infection cured after direct-acting antiviral therapy; validation set 3 (V3): 146 patients with advanced liver fibrosis with successfully-treated HCC and cured HCV infection.

Findings: An 8-protein blood-based PLSec recapitulated transcriptome-based hepatic HCC risk status. In V1, PLSec was significantly associated with incident HCC risk (adjusted hazard ratio [aHR], 2.35; 95% confidence interval [CI], 1.30-4.23). A composite score with serum alpha-fetoprotein (PLSec-AFP) was defined in V1, and validated in V2 (adjusted odds ratio, 3.80 [95%CI, 1.66-8.66]) and V3 (aHR, 3.08 [95%CI, 1.78-5.31]; c-index, 0.74). PLSec-AFP outperformed AFP alone (Brier score, 0.165 vs. 0.186 in V2; 0.196 vs. 0.206 in V3, respectively).

Conclusions: The blood-based PLSec-AFP can accurately stratify patients with advanced liver fibrosis for long-term HCC risk and thereby guide risk-based tailored HCC screening.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.medj.2021.03.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312635PMC
July 2021

Increase in muscle mass associated with the prebiotic effects of 1-kestose in super-elderly patients with sarcopenia.

Biosci Microbiota Food Health 2021 20;40(3):150-155. Epub 2021 Feb 20.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi-dori, Chuo-ku, Niigata, Niigata 951-8510, Japan.

Sarcopenia causes functional disorders and decreases the quality of life. Thus, it has attracted substantial attention in the aging modern world. Dysbiosis of the intestinal microbiota is associated with sarcopenia; however, it remains unclear whether prebiotics change the microbiota composition and result in the subsequent recovery of muscle atrophy in elderly patients with sarcopenia. This study aimed to assess the effects of prebiotics in super-elderly patients with sarcopenia. We analyzed the effects of 1-kestose on the changes in the intestinal microbiota and body composition using a next-generation sequencer and a multi-frequency bioimpedance analysis device. The population was significantly increased in the intestine after 1-kestose administration. In addition, in all six patients after 12 weeks of 1-kestose administration, the skeletal muscle mass index was greater, and the body fat percentage was lower. This is the first study to show that administration of a prebiotic increased the population of in the intestinal microbiota and caused recovery of muscle atrophy in super-elderly patients with sarcopenia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12938/bmfh.2020-063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279888PMC
February 2021

Dynamic Changes in Ultrasound Quality for Hepatocellular Carcinoma Screening in Patients With Cirrhosis.

Clin Gastroenterol Hepatol 2021 Jun 10. Epub 2021 Jun 10.

Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas; Parkland Health & Hospital System, Dallas, Texas. Electronic address:

Background & Aims: Identifying patients in whom ultrasound may be inadequate to exclude the presence of hepatocellular carcinoma (HCC) can inform interventions to improve screening effectiveness. We aimed to characterize correlates of suboptimal ultrasound quality and changes in ultrasound quality over time in patients with cirrhosis undergoing HCC screening.

Methods: We performed a retrospective cohort study of patients with cirrhosis who underwent ultrasound examination at 2 large health systems between July 2016 and July 2019. Exam adequacy was graded by radiologists using the LI-RADS Visualization Score (A, B, C); we evaluated changes in visualization over time among patients with >1 ultrasound exams. We performed multivariable logistic regression to identify characteristics associated with limited ultrasound visualization (scores B or C).

Results: Of 2053 cirrhosis patients, 1685 (82.1%) had ultrasounds with score A, 262 (12.8%) had score B, and 106 (5.2%) had score C. Limited visualization was associated with alcohol-related or nonalcoholic fatty liver disease cirrhosis and presence of class II-III obesity. Among 1546 patients with >1 ultrasounds, 1129 (73.0%) had the same visualization score on follow-up (1046 score A, 60 score B, 23 score C). However, 255 (19.6%) of 1301 with score A at baseline had limited visualization when repeated (230 score B, 25 score C), and 130 (53.1%) of 245 patients with baseline limited visualization had good visualization when repeated.

Conclusions: Nearly 1 in 5 patients with cirrhosis had moderately-severely limited ultrasound visualization for HCC nodules, particularly those with obesity or alcohol-related or nonalcoholic fatty liver disease cirrhosis. Ultrasound quality can change between exams, including improvement in many patients with limited visualization.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cgh.2021.06.012DOI Listing
June 2021

Multisite multivendor validation of a quantitative MRI and CT compatible fat phantom.

Med Phys 2021 Aug 9;48(8):4375-4386. Epub 2021 Jul 9.

Department of Radiology, University of Wisconsin-Madison, Madison, WI, USA.

Purpose: Chemical shift-encoded magnetic resonance imaging enables accurate quantification of liver fat content though estimation of proton density fat-fraction (PDFF). Computed tomography (CT) is capable of quantifying fat, based on decreased attenuation with increased fat concentration. Current quantitative fat phantoms do not accurately mimic the CT number of human liver. The purpose of this work was to develop and validate an optimized phantom that simultaneously mimics the MRI and CT signals of fatty liver.

Methods: An agar-based phantom containing 12 vials doped with iodinated contrast, and with a granular range of fat fractions was designed and constructed within a novel CT and MR compatible spherical housing design. A four-site, three-vendor validation study was performed. MRI (1.5T and 3T) and CT images were obtained using each vendor's PDFF and CT reconstruction, respectively. An ROI centered in each vial was placed to measure MRI-PDFF (%) and CT number (HU). Mixed-effects model, linear regression, and Bland-Altman analysis were used for statistical analysis.

Results: MRI-PDFF agreed closely with nominal PDFF values across both field strengths and all MRI vendors. A linear relationship (slope = -0.54 ± 0.01%/HU, intercept = 37.15 ± 0.03%) with an R of 0.999 was observed between MRI-PDFF and CT number, replicating established in vivo signal behavior. Excellent test-retest repeatability across vendors (MRI: mean = -0.04%, 95% limits of agreement = [-0.24%, 0.16%]; CT: mean = 0.16 HU, 95% limits of agreement = [-0.15HU, 0.47HU]) and good reproducibility using GE scanners (MRI: mean = -0.21%, 95% limits of agreement = [-1.47%, 1.06%]; CT: mean = -0.18HU, 95% limits of agreement = [-1.96HU, 1.6HU]) were demonstrated.

Conclusions: The proposed fat phantom successfully mimicked quantitative liver signal for both MRI and CT. The proposed fat phantom in this study may facilitate broader application and harmonization of liver fat quantification techniques using MRI and CT across institutions, vendors and imaging platforms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mp.15038DOI Listing
August 2021

Long-term survival of 11 years with multidisciplinary therapy for hepatocellular carcinoma metastasis to the ovary and peritoneum: a case report.

Clin J Gastroenterol 2021 Aug 12;14(4):1211-1220. Epub 2021 May 12.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan.

We herein report a rare case of HCC metastases to the ovary and peritoneum in a 61-year-old female patient who has achieved 11-year survival with multidisciplinary therapy. The patient was diagnosed with HCC during balloon angioplasty performed for Budd-Chiari syndrome in 1994 and underwent partial hepatectomy twice. Five years after the second hepatectomy, allochronic recurrence of a single nodule detected in S8 was treated by radiofrequency ablation, followed by percutaneous ethanol injection therapy and stereotactic body radiotherapy. However, her α-fetoprotein level rose to 1862 ng/mL within one year and computed tomography revealed a large pelvic tumor suggesting HCC metastasis to the ovary. The subsequent laparotomy revealed one 11-cm left ovarian tumor, one small right ovarian nodule, and numerous peritoneal nodules. Bilateral salpingo-oophorectomy and peritoneal resection of as many nodules as possible were performed. Combination therapy with intravenous 5-fluorouracil plus cisplatin and ramucirumab monotherapy effectively suppressed tumor progression with maintenance of hepatic functional reserve, and she has achieved long-term survival of 11 years, illustrating that multidisciplinary therapy with favorable hepatic functional reserve maintenance can contribute to long-term survival in HCC with extrahepatic spread.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12328-021-01434-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298212PMC
August 2021

High Neutrophil-Lymphocyte Ratio and Delta Neutrophil-Lymphocyte Ratio Are Associated with Increased Mortality in Patients with Hepatocellular Cancer.

Dig Dis Sci 2021 May 3. Epub 2021 May 3.

Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, 5959 Harry Hines Blvd, POB 1, Suite 420, Dallas, TX, 75390-8887, USA.

Background: The neutrophil-lymphocyte ratio (NLR) has been proposed as a prognostic biomarker for cirrhosis and non-liver malignancies. We aimed to evaluate the prognostic value of NLR in a diverse cohort of patients with hepatocellular carcinoma (HCC).

Methods: We performed a retrospective study of patients diagnosed with HCC between 2008 and 2017 at two large US health systems. We used Cox proportional hazard and multivariable ordinal logistic regression models to identify factors associated with overall survival and response to first HCC treatment, respectively. Primary variables of interest were baseline NLR and delta NLR, defined as the difference between pre- and post-treatment NLR.

Results: Among 1019 HCC patients, baseline NLR was < 5 in 815 (80.0%) and ≥ 5 in 204 (20.0%). Patients with NLR ≥ 5 had a higher proportion of infiltrative tumors (36.2% vs 22.3%), macrovascular invasion (39.6% vs 25.5%), metastatic disease (20.6% vs 11.4%), and AFP > 200 ng/mL (45.6% vs 33.8%). Baseline NLR ≥ 5 was independently associated with higher mortality (median survival 4.3 vs 15.1 months; adjusted HR 1.70, 95%CI 1.41-2.06), with differences in survival consistent across BCLC stages. After adjusting for baseline covariates including NLR, delta NLR > 0.26 was also independently associated with increased mortality (HR 1.42, 95%CI 1.14-1.78). In a secondary analysis, high NLR was associated with lower odds of response to HCC treatment (20.2% vs 31.6%; adjusted OR 0.55, 95%CI 0.32-0.95).

Conclusions: In a large Western cohort of patients with HCC, high baseline NLR and delta NLR were independent predictors of mortality.

Impact: NLR is an inexpensive test that may be a useful component of future HCC prognostic models.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10620-021-07001-6DOI Listing
May 2021

Modulation of serotonin in the gut-liver neural axis ameliorates the fatty and fibrotic changes in non-alcoholic fatty liver.

Dis Model Mech 2021 03 28;14(3). Epub 2021 Mar 28.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8510, Japan.

The etiology of non-alcoholic fatty liver disease (NAFLD) consists of various factors, including neural signal pathways. However, the molecular mechanisms of the autonomic neural signals influencing NAFLD progression have not been elucidated. Therefore, we examined the involvement of the gut-liver neural axis in NAFLD development and tested the therapeutic effect of modulation of this axis in this study. To test the contribution of the gut-liver neural axis, we examined NAFLD progression with respect to body weight, hepatic steatosis, fibrosis, intestinal tight junction, microbiota and short-chain fatty acids in NAFLD models of choline-deficient defined L-amino-acid and high-fat diet-fed mice with or without blockades of autonomic nerves from the liver. Blockade of the neural signal from the liver to the gut in these NAFLD mice models ameliorated the progression of liver weight, hepatic steatosis and fibrosis by modulating serotonin expression in the small intestine. It was related to the severity of the liver pathology, the tight junction protein expression, microbiota diversity and short-chain fatty acids. These effects were reproduced by administrating serotonin antagonist, which ameliorated the NAFLD progression in the NAFLD mice models. Our study demonstrated that the gut-liver neural axis is involved in the etiologies of NAFLD progression and that serotonin expression through this signaling network is the key factor of this axis. Therefore, modulation of the gut-liver neural axis and serotonin antagonist ameliorates fatty and fibrotic changes in non-alcoholic fatty liver, and can be a potential therapeutic target of NAFLD.This article has an associated First Person interview with the first author of the paper.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1242/dmm.048922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084356PMC
March 2021

LI-RADS treatment response algorithm after first-line DEB-TACE: reproducibility and prognostic value at initial post-treatment CT/MRI.

Abdom Radiol (NY) 2021 08 23;46(8):3708-3716. Epub 2021 Mar 23.

Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Purpose: To evaluate the inter-reader reproducibility and prognostic accuracy of the Liver Imaging Reporting and Data System (LI-RADS) treatment response algorithm (LR-TR) at the time of initial post-treatment evaluation following drug-eluting beads transarterial chemoembolization (DEB-TACE) for hepatocellular carcinoma (HCC).

Methods: This retrospective study included patients with HCC who underwent first-line DEB-TACE between January 2011 and December 2015. Six readers (three fellowship-trained radiologists and three radiology trainees) independently assessed lesion-level response in up to two treated lesions per LR-TR and modified Response Evaluation Criteria in Solid Tumors (mRECIST)-target criteria, as well as patient-level response per mRECIST-overall criteria, on the initial post-treatment CT/MRI. Inter-reader agreement was calculated by Fleiss' multi-reader κ. We tested whether LR-TR, mRECIST-target, and mRECIST-overall response were associated with overall survival using Kaplan-Meier and Cox proportional hazard model analyses.

Results: A total of 82 patients with 113 treated target lesions were included. Inter-reader agreement was moderate for LR-TR and mRECIST-overall (κ range 0.42-0.57), and substantial for mRECIST-target (κ range 0.62-0.66), among all three reader-groups: all readers, experienced readers, and less-experienced readers. LR-TR and mRECIST-target response were not significantly associated with overall survival regardless of reader experience (P > 0.05). In contrast, mRECIST-overall response was significantly associated with overall survival when assessed by all readers (P = 0.02) and experienced readers (P = 0.03), but not by the less-experienced readers (P = 0.35).

Conclusion: Although LR-TR algorithm has moderate inter-reader reproducibility, it alone may not predict overall survival on the initial post-treatment CT/MRI after first-line DEB-TACE for HCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00261-021-03043-6DOI Listing
August 2021

Adipose most abundant 2 protein is a predictive marker for cisplatin sensitivity in cancers.

Sci Rep 2021 03 18;11(1):6255. Epub 2021 Mar 18.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi-dori, Chuo-ku, Niigata, Niigata, 951-8510, Japan.

Cisplatin (CDDP) is one of the chemotherapeutic drugs being used to treat various cancers. Although effective in many cases, as high doses of CDDP cause cytotoxic effects that may worsen patients' condition, therefore, a marker of sensitivity to CDDP is necessary to enhance the safety and efficiency of CDDP administration. This study focused on adipose most abundant 2 (APM2) to examine its potential as a marker of CDDP sensitivity. The relationship of APM2 expression with the mechanisms of CDDP resistance was examined in vitro and in vivo using hepatocellular carcinoma (HCC) cells, tissues and serum of HCC patients (n = 71) treated initially with intrahepatic arterial infusion of CDDP followed by surgical resection. The predictability of serum APM2 for CDDP sensitivity was assessed in additional 54 HCC patients and 14 gastric cancer (GC) patients. APM2 expression in CDDP-resistant HCC was significantly higher both in serum and the tissue. Bioinformatic analyses and histological analyses demonstrated upregulation of ERCC6L (DNA excision repair protein ERCC6-like) by APM2, which accounts for the degree of APM2 expression. The serum APM2 level and chemosensitivity for CDDP were assessed and cut-off value of serum APM2 for predicting the sensitivity to CDDP was determined to be 18.7 µg/mL. The value was assessed in HCC (n = 54) and GC (n = 14) patients for its predictability of CDDP sensitivity, resulted in predictive value of 77.3% and 100%, respectively. Our study demonstrated that APM2 expression is related to CDDP sensitivity and serum APM2 can be an effective biomarker of HCC and GC for determining the sensitivity to CDDP.Trial registration: This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000028487).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-85498-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973578PMC
March 2021

Temperature-corrected proton density fat fraction estimation using chemical shift-encoded MRI in phantoms.

Magn Reson Med 2021 07 9;86(1):69-81. Epub 2021 Feb 9.

Department of Medical Physics, University of Wisconsin - Madison, Madison, Wisconsin, USA.

Purpose: Chemical shift-encoded MRI (CSE-MRI) is well-established to quantify proton density fat fraction (PDFF) as a quantitative biomarker of hepatic steatosis. However, temperature is known to bias PDFF estimation in phantom studies. In this study, strategies were developed and evaluated to correct for the effects of temperature on PDFF estimation through simulations, temperature-controlled experiments, and a multi-center, multi-vendor phantom study.

Theory And Methods: A technical solution that assumes and automatically estimates a uniform, global temperature throughout the phantom is proposed. Computer simulations modeled the effect of temperature on PDFF estimation using magnitude-, complex-, and hybrid-based CSE-MRI methods. Phantom experiments were performed to assess the temperature correction on PDFF estimation at controlled phantom temperatures. To assess the temperature correction method on a larger scale, the proposed method was applied to data acquired as part of a nine-site multi-vendor phantom study and compared to temperature-corrected PDFF estimation using an a priori guess for ambient room temperature.

Results: Simulations and temperature-controlled experiments show that as temperature deviates further from the assumed temperature, PDFF bias increases. Using the proposed correction method and a reasonable a priori guess for ambient temperature, PDFF bias and variability were reduced using magnitude-based CSE-MRI, across MRI systems, field strengths, protocols, and varying phantom temperature. Complex and hybrid methods showed little PDFF bias and variability both before and after correction.

Conclusion: Correction for temperature reduces temperature-related PDFF bias and variability in phantoms across MRI vendors, sites, field strengths, and protocols for magnitude-based CSE-MRI, even without a priori information about the temperature.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mrm.28669DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432757PMC
July 2021

Linearity and Bias of Proton Density Fat Fraction as a Quantitative Imaging Biomarker: A Multicenter, Multiplatform, Multivendor Phantom Study.

Radiology 2021 03 19;298(3):640-651. Epub 2021 Jan 19.

From the Department of Radiology, Nationwide Children's Hospital, 700 Children's Dr, Columbus, OH 43235 (H.H.H., M.A.S.); Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Tex (T.Y.); Department of Radiology (M.R.B., J.S.), Department of Medicine, Division of Gastroenterology (M.R.B.), and Center for Advanced Magnetic Resonance Development (M.R.B., J.S.), Duke University Medical Center, Durham, NC; Liver Imaging Group, Department of Radiology, University of California San Diego, San Diego, Calif (C.B.S., M.S.M., W.C.H., G.H.); Departments of Radiology (D.H., J.H.B., S.B.R.), Medical Physics (D.H., E.F.J., S.B.R.), Biomedical Engineering (S.B.R.), Medicine (S.B.R.), and Emergency Medicine (S.B.R.), University of Wisconsin, Madison, Wis; Department of Radiology, University of Michigan, Ann Arbor, Mich (D.M., T.L.C.); Department of Radiology, Children's Hospital of Philadelphia, Philadelphia, Pa (S.D.S.); Department of Radiology, Mayo Clinic, Rochester, Minn (Y.S.); Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio (J.A.T., A.T.T.); Department of Radiology, University of Cincinnati College of Medicine, Cincinnati, Ohio (J.A.T., A.T.T.); Department of Quantitative Health Science, Cleveland Clinic Foundation, Cleveland, Ohio (N.O.); and Calimetrix, LLC, Madison, Wis (J.H.B.).

Background Proton density fat fraction (PDFF) estimated by using chemical shift-encoded (CSE) MRI is an accepted imaging biomarker of hepatic steatosis. This work aims to promote standardized use of CSE MRI to estimate PDFF. Purpose To assess the accuracy of CSE MRI methods for estimating PDFF by determining the linearity and range of bias observed in a phantom. Materials and Methods In this prospective study, a commercial phantom with 12 vials of known PDFF values were shipped across nine U.S. centers. The phantom underwent 160 independent MRI examinations on 27 1.5-T and 3.0-T systems from three vendors. Two three-dimensional CSE MRI protocols with minimal T1 bias were included: vendor and standardized. Each vendor's confounder-corrected complex or hybrid magnitude-complex based reconstruction algorithm was used to generate PDFF maps in both protocols. The Siemens reconstruction required a configuration change to correct for water-fat swaps in the phantom. The MRI PDFF values were compared with the known PDFF values by using linear regression with mixed-effects modeling. The 95% CIs were calculated for the regression slope (ie, proportional bias) and intercept (ie, constant bias) and compared with the null hypothesis (slope = 1, intercept = 0). Results Pooled regression slope for estimated PDFF values versus phantom-derived reference PDFF values was 0.97 (95% CI: 0.96, 0.98) in the biologically relevant 0%-47.5% PDFF range. The corresponding pooled intercept was -0.27% (95% CI: -0.50%, -0.05%). Across vendors, slope ranges were 0.86-1.02 (vendor protocols) and 0.97-1.0 (standardized protocol) at 1.5 T and 0.91-1.01 (vendor protocols) and 0.87-1.01 (standardized protocol) at 3.0 T. The intercept ranges (absolute PDFF percentage) were -0.65% to 0.18% (vendor protocols) and -0.69% to -0.17% (standardized protocol) at 1.5 T and -0.48% to 0.10% (vendor protocols) and -0.78% to -0.21% (standardized protocol) at 3.0 T. Conclusion Proton density fat fraction estimation derived from three-dimensional chemical shift-encoded MRI in a commercial phantom was accurate across vendors, imaging centers, and field strengths, with use of the vendors' product acquisition and reconstruction software. © RSNA, 2021 See also the editorial by Dyke in this issue.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1148/radiol.2021202912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924516PMC
March 2021

Alternative approach of hepatocellular carcinoma surveillance: abbreviated MRI.

Hepatoma Res 2020 1;6. Epub 2020 Sep 1.

Department of Radiology, Naval Medical Center San Diego, San Diego, CA 92134, USA.

This review focuses on emerging abbreviated magnetic resonance imaging (AMRI) surveillance of patients with chronic liver disease for hepatocellular carcinoma (HCC). This surveillance strategy has been proposed as a high-sensitivity alternative to ultrasound for identification of patients with early-stage HCC, particularly in patients with cirrhosis or obesity, in whom sonographic visualization of small tumors may be compromised. Three general AMRI approaches have been developed and studied in the literature - non-contrast AMRI, dynamic contrast-enhanced AMRI, and hepatobiliary phase contrast-enhanced AMRI - each comprising a small number of selected sequences specifically tailored for HCC detection. The rationale, general technique, advantages and disadvantages, and diagnostic performance of each AMRI approach is explained. Additionally, current gaps in knowledge and future directions are discussed. Based on emerging evidence, we cautiously recommend the use of AMRI for HCC surveillance in situations where ultrasound is compromised.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.20517/2394-5079.2020.50DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771881PMC
September 2020

Long-Term Results of a Phase 1 Dose-Escalation Trial and Subsequent Institutional Experience of Single-Fraction Stereotactic Ablative Radiation Therapy for Liver Metastases.

Int J Radiat Oncol Biol Phys 2021 04 16;109(5):1387-1395. Epub 2020 Dec 16.

Department of Radiation Oncology, UT Southwestern Medical Center, Dallas, Texas.

Purpose: We report long-term outcomes from our phase 1 dose-escalation study to determine the maximum tolerated dose of single-fraction liver SABR pooled with our subsequent single institutional experience with patients treated postprotocol at the highest dose level (40 Gy) established from the phase 1 study.

Methods And Materials: Patients with liver metastases from solid tumors located outside of the central liver zone were treated with single-fraction SABR on a phase 1 dose escalation trial. At least 700 cc of normal liver had to receive <9.1 Gy. Seven patients with 10 liver metastases received the initial prescription dose of 35 Gy, and dose was then escalated to 40 Gy for 7 more patients with 7 liver metastases. An additional 19 postprotocol patients with 22 liver metastases were treated to 40 Gy in a single fraction. Patients were followed for toxicity and underwent serial imaging to assess local control.

Results: Median imaging follow-up for the combined cohort (n = 33, 39 lesions) was 25.9 months; 38.9 months for protocol patients and 20.2 months for postprotocol patients. Median lesion size was 2.0 cm (range, 0.5-5.0 cm). There were no dose-limiting toxicities observed for protocol patients, and only 3 grade 2 toxicities were observed in the entire cohort, with no grade ≥3 toxicities attributable to treatment. Four-year actuarial local control of irradiated lesions in the entire cohort was 96.6%, 100% in the protocol group and 92.9% in the subsequent patients. Two-year overall survival for all treated patients was 82.0%.

Conclusions: For selected patients with liver metastases, single-fraction SABR at doses of 35 and 40 Gy was safe and well-tolerated, and shows excellent local control with long-term follow-up; results in subsequent patients treated with single-fraction SABR doses of 40 Gy confirmed our earlier results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijrobp.2020.12.012DOI Listing
April 2021

Daily Monitoring of Serum Wisteria floribunda Agglutinin-Positive Mac-2 Binding Protein Is Useful for Predicting Therapeutic Effect of Tolvaptan in Cirrhotic Ascites.

Tohoku J Exp Med 2020 12;252(4):287-296

Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences.

Wisteria floribunda agglutinin (WFA) is a lectin that binds to the sugar chain of Mac-2 binding protein (M2BP), and WFA-positive M2BP (WFA-M2BP) has been reported as a useful marker for assessing liver fibrosis in chronic liver disease. Tolvaptan (TLV), a selective vasopressin V2 receptor antagonist, is used for cirrhotic ascites in Japan, but good predictors of treatment efficacy remain to be established. Our aim was to investigate whether WFA-M2BP monitoring before and after TLV administration can predict treatment efficacy in patients with cirrhotic ascites. Twenty patients (10 men), with a median age of 72 years, were enrolled. Cirrhosis was caused by hepatitis B virus (n = 3), hepatitis C virus (n = 4), alcohol (n = 8), and others (n = 5). Responders were defined as having a body weight loss of ≥ 1.5 kg/week after TLV administration. Serum WFA-M2BP levels were measured at baseline and days 1, 3, and 7 after TLV treatment. Twelve patients (60%) were responders. Baseline WFA-M2BP levels were correlated with serum albumin levels (r = -0.544, P = 0.013). The baseline furosemide dose was lower and platelet count was higher in responders than in non-responders (P < 0.05). The ratio of WFA-M2BP levels on day 1 after TLV administration to baseline was lower in responders than in non-responders (P < 0.05). The decrease in the ratio discriminated responders from non-responders (AUC = 0.844, P < 0.05). In conclusion, monitoring serum WFA-M2BP is helpful for predicting the efficacy of TLV treatment in patients with cirrhotic ascites.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1620/tjem.252.287DOI Listing
December 2020

Abbreviated MRI for Hepatocellular Carcinoma Screening and Surveillance.

Radiographics 2020 Nov-Dec;40(7):1916-1931

From the Liver Imaging Group, Department of Radiology, University of California San Diego, 9500 Gilman Dr, MC 0888, San Diego, CA 92093 (J.Y.A., G.M.C., M.T.B., C.B.S., K.J.F.); School of Medicine, Tufts University, Boston, Mass (M.A.P.); Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Tex (B.T.); and Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, NY (T.Y.).

To detect potentially curable hepatocellular carcinoma (HCC), clinical practice guidelines recommend semiannual surveillance US of the liver in adult patients at risk for developing this malignancy, such as those with cirrhosis and some patients with chronic hepatitis B infection. However, cirrhosis and a large body habitus, both of which are increasingly prevalent in the United States and the rest of the world, may impair US visualization of liver lesions and reduce the sensitivity of surveillance with this modality. The low sensitivity of US for detection of early-stage HCC contributes to delayed diagnosis and increased mortality. Abbreviated MRI, a shortened MRI protocol tailored for early-stage detection of HCC, has been proposed as an alternative surveillance option that provides high sensitivity and specificity. Abbreviated MRI protocols include fewer sequences than a complete multiphase MRI examination and are specifically designed to identify small potentially curable HCCs that may be missed at US. Three abbreviated MRI strategies have been studied: nonenhanced, dynamic contrast material-enhanced, and hepatobiliary phase contrast-enhanced abbreviated MRI. Retrospective studies have shown that simulated abbreviated MRI provides high sensitivity and specificity for early-stage HCC, mostly in nonsurveillance cohorts. If it is supported by scientific evidence in surveillance populations, adoption of abbreviated MRI could advance clinical practice by increasing early detection of HCC, allowing effective treatment and potentially prolonging life in the growing number of individuals with this cancer. RSNA, 2020.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1148/rg.2020200104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7714535PMC
July 2021

Efficacy and Safety of the Radiotherapy for Liver Cancer: Assessment of Local Controllability and its Role in Multidisciplinary Therapy.

Cancers (Basel) 2020 Oct 13;12(10). Epub 2020 Oct 13.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachido-ri, Chuo-ku, Niigata, Niigata, 951-8510, Japan.

This study investigated the efficacy and safety of radiotherapy as part of multidisciplinary therapy for advanced hepatocellular carcinoma (HCC). Clinical data of 49 HCC patients treated with radiotherapy were assessed retrospectively. The efficacy of radiotherapy was assessed by progression-free survival, disease control rate, and overall survival. Safety was assessed by symptoms and hematological assay, and changes in hepatic reserve function were determined by Child-Pugh score and albumin-bilirubin (ALBI) score. Forty patients underwent curative radiotherapy, and nine patients with portal vein tumor thrombus (PVTT) underwent palliative radiotherapy as part of multidisciplinary therapy. Local disease control for curative therapy was 80.0% and stereotactic body radiotherapy was 86.7% which was greater than that of conventional radiotherapy (60.0%). Patients with PVTT had a median observation period of 651 days and 75% three-year survival when treated with multitherapy, including radiotherapy for palliative intent, transcatheter arterial chemoembolization, and administration of molecular targeted agents. No adverse events higher than grade 3 and no changes in the Child-Pugh score and ALBI score were seen. Radiotherapy is safe and effective for HCC treatment and can be a part of multidisciplinary therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers12102955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601963PMC
October 2020

Pearls and Pitfalls of Metabolic Liver Magnetic Resonance Imaging in the Pediatric Population.

Semin Ultrasound CT MR 2020 Oct 28;41(5):451-461. Epub 2020 May 28.

Department of Radiology, University of Texas Southwestern School of Medicine, Dallas, TX.

Recent advances in magnetic resonance imaging (MRI) technology have moved imaging beyond anatomical assessment to characterization of tissue composition. There are now clinically validated MRI-based quantitative techniques for assessing liver fat, iron, and fibrosis, and MRI is now routinely used in metabolic liver disease evaluation in both pediatric and adult patients. These MRI techniques provide noninvasive quantitation of liver metabolic biomarkers that are increasingly relied upon in the clinical management of pediatric patients with nonalcoholic fatty liver disease, metabolic syndrome, and hemochromatosis and/or hemosiderosis. This article provides a review of the clinical indications and technical parameters for performing metabolic liver MRI in the pediatric population, along with common pearls and pitfalls encountered during its performance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.sult.2020.05.010DOI Listing
October 2020

Prospective performance of clear cell likelihood scores (ccLS) in renal masses evaluated with multiparametric magnetic resonance imaging.

Eur Radiol 2021 Jan 8;31(1):314-324. Epub 2020 Aug 8.

Department of Urology, University of Texas Southwestern, Dallas, TX, USA.

Objectives: Solid renal masses have unknown malignant potential with commonly utilized imaging. Biopsy can offer a diagnosis of cancer but has a high non-diagnostic rate and complications. Reported use of multiparametric magnetic resonance imaging (mpMRI) to diagnose aggressive histology (i.e., clear cell renal cell carcinoma (ccRCC)) via a clear cell likelihood score (ccLS) was based on retrospective review of cT1a tumors. We aim to retrospectively assess the diagnostic performance of ccLS prospectively assigned to renal masses of all stages evaluated with mpMRI prior to histopathologic evaluation.

Methods: In this retrospective cohort study from June 2016 to November 2019, 434 patients with 454 renal masses from 2 institutions with heterogenous patient populations underwent mpMRI with prospective ccLS assignment and had pathologic diagnosis. ccLS performance was assessed by contingency table analysis. The association between ccLS and ccRCC was assessed with logistic regression.

Results: Mean age and tumor size were 60 ± 13 years and 5.4 ± 3.8 cm. Characteristics were similar between institutions except for patient age and race (both p < 0.001) and lesion laterality and histology (both p = 0.04). The PPV of ccLS increased with each increment in ccLS (ccLS1 5% [3/55], ccLS2 6% [3/47], ccLS3 35% [20/57], ccLS4 78% [85/109], ccLS5 93% [173/186]). Pooled analysis for ccRCC diagnosis revealed sensitivity 91% (258/284), PPV 87% (258/295) for ccLS ≥ 4, and specificity 56% (96/170), NPV 94% (96/102) for ccLS ≤ 2. Diagnostic performance was similar between institutions.

Conclusions: We confirm the optimal diagnostic performance of mpMRI to identify ccRCC in all clinical stages. High PPV and NPV of ccLS can help inform clinical management decision-making.

Key Points: • The positive predictive value of the clear cell likelihood score (ccLS) for detecting clear cell renal cell carcinoma was 5% (ccLS1), 6% (ccLS2), 35% (ccLS3), 78% (ccLS4), and 93% (ccLS5). Sensitivity of ccLS ≥ 4 and specificity of ccLS ≤ 2 were 91% and 56%, respectively. • When controlling for confounding variables, ccLS is an independent risk factor for identifying clear cell renal cell carcinoma. • Utilization of the ccLS can help guide clinical care, including the decision for renal mass biopsy, reducing the morbidity and risk to patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00330-020-07093-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755825PMC
January 2021

Hepatocellular carcinoma tumour volume doubling time: a systematic review and meta-analysis.

Gut 2021 02 12;70(2):401-407. Epub 2020 May 12.

Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA

Background: Tumour growth patterns have important implications for surveillance intervals, prognostication and treatment decisions but have not been well described for hepatocellular carcinoma (HCC). The aim of our study was to characterise HCC doubling time and identify correlates for indolent and rapid growth patterns.

Methods: We performed a systematic literature review of Medline and EMBASE databases from inception to December 2019 and national meeting abstracts from 2010 to 2018. We identified studies reporting HCC tumour growth or tumour volume doubling time (TVDT), without intervening treatment, and abstracted data to calculate TVDT and correlates of growth patterns (rapid defined as TVDT <3 months and indolent as TVDT >9 months). Pooled TVDT was calculated using a random-effects model.

Results: We identified 20 studies, including 1374 HCC lesions in 1334 patients. The pooled TVDT was 4.6 months (95% CI 3.9 to 5.3 months I=94%), with 35% classified as rapid, 27.4% intermediate and 37.6% indolent growth. In subgroup analysis, studies from Asia reported shorter TVDT than studies elsewhere (4.1 vs 5.8 months). The most consistent correlates of rapid tumour growth included hepatitis B aetiology, smaller tumour size (continuous), alpha fetoprotein doubling time and poor tumour differentiation. Studies were limited by small sample sizes, measurement bias and selection bias.

Conclusion: TVDT of HCC is approximately 4-5 months; however, there is heterogeneity in tumour growth patterns, including more aggressive patterns in Asian hepatitis B-predominant populations. Identifying correlates of tumour growth patterns is important to better individualise HCC prognostication and treatment decisions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/gutjnl-2020-321040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7657990PMC
February 2021

21st Century Advances in Multimodality Imaging of Obesity for Care of the Cardiovascular Patient.

JACC Cardiovasc Imaging 2021 02 15;14(2):482-494. Epub 2020 Apr 15.

Department of Cardiology, John Ochsner Heart and Vascular Institute, Ochsner Clinical School, the University of Queensland School of Medicine, New Orleans, Louisiana, USA.

Although obesity is typically defined by body mass index criteria, this does not differentiate true body fatness, as this includes both body fat and muscle. Therefore, other fat depots may better define cardiometabolic and cardiovascular disease (CVD) risk imposed by obesity. Data from translational, epidemiological, and clinical studies over the past 3 decades have clearly demonstrated that accumulation of adiposity in the abdominal viscera and within tissue depots lacking physiological adipose tissue storage capacity (termed "ectopic fat") is strongly associated with the development of a clinical syndrome characterized by atherogenic dyslipidemia, hyperinsulinemia/glucose intolerance/type 2 diabetes mellitus, hypertension, atherosclerosis, and abnormal cardiac remodeling and heart failure. This state-of-the-art paper discusses the impact of various body fat depots on cardiometabolic parameters and CVD risk. Specifically, it reviews novel and emerging imaging techniques to evaluate adiposity and the risk of cardiometabolic diseases and CVD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcmg.2020.02.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554055PMC
February 2021

Effect of Diphtheria Toxin-Based Gene Therapy for Hepatocellular Carcinoma.

Cancers (Basel) 2020 Feb 18;12(2). Epub 2020 Feb 18.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata 951-8510, Japan.

Hepatocellular carcinoma (HCC) is a major global malignancy, responsible for >90% of primary liver cancers. Currently available therapeutic options have poor performances due to the highly heterogeneous nature of the tumor cells; recurrence is highly probable, and some patients develop resistances to the therapies. Accordingly, the development of a novel therapy is essential. We assessed gene therapy for HCC using a diphtheria toxin fragment A (DTA) gene-expressing plasmid, utilizing a non-viral hydrodynamics-based procedure. The antitumor effect of DTA expression in HCC cell lines (and alpha-fetoprotein (AFP) promoter selectivity) is assessed in vitro by examining HCC cell growth. Moreover, the effect and safety of the AFP promoter-selective DTA expression was examined in vivo using an HCC mice model established by the hydrodynamic gene delivery of the yes-associated protein (YAP)-expressing plasmid. The protein synthesis in DTA transfected cells is inhibited by the disappearance of tdTomato and GFP expression co-transfected upon the delivery of the DTA plasmid; the HCC cell growth is inhibited by the expression of DTA in HCC cells in an AFP promoter-selective manner. A significant inhibition of HCC occurrence and the suppression of the tumor marker of AFP and des-gamma-carboxy prothrombin can be seen in mice groups treated with hydrodynamic gene delivery of DTA, both 0 and 2 months after the YAP gene delivery. These results suggest that DTA gene therapy is effective for HCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers12020472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072394PMC
February 2020

Ghrelin-insulin-like growth factor-1 axis is activated via autonomic neural circuits in the non-alcoholic fatty liver disease.

Neurogastroenterol Motil 2020 05 27;32(5):e13799. Epub 2020 Jan 27.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.

Background: The correlation of the growth hormone (GH) and insulin-like growth factor-1 (IGF-1) with non-alcoholic fatty liver disease (NAFLD) has been reported in epidemiological studies. However, the mechanisms of molecular and inter-organ systems that render these factors to influence on NAFLD have not been elucidated. In this study, we examined the induction of ghrelin which is the GH-releasing hormone and IGF-1, and involvement of autonomic neural circuits, in the pathogenesis of NAFLD.

Methods: The expression of gastric and hypothalamic ghrelin, neural activation in the brain, and serum IGF-1 were examined in NAFLD models of choline-deficient defined l-amino-acid diet-fed, melanocortin 4 receptor knockout mice, and partial hepatectomy mice with or without the blockades of autonomic nerves to test the contribution of neural circuits connecting the brain, liver, and stomach.

Key Results: The fatty changes in the liver increased the expression of gastric ghrelin through the autonomic pathways which sends the neural signals to the arcuate nucleus in the hypothalamus through the afferent vagal nerve which reached the pituitary gland to release GH and then stimulate the IGF-1 release from the liver. In addition, high levels of ghrelin expression in the arcuate nucleus were correlated with NAFLD progression regardless of the circuits.

Conclusions: Our study demonstrated that the fatty liver stimulates the autonomic nervous signal circuits which suppress the progression of the disease by activating the gastric ghrelin expression, the neural signal transduction in the brain, and the release of IGF-1 from the liver.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/nmo.13799DOI Listing
May 2020

Assessment of hepatocellular carcinoma treatment response with LI-RADS: a pictorial review.

Insights Imaging 2019 Dec 18;10(1):121. Epub 2019 Dec 18.

Department of Radiology, Centre hospitalier de l'Université de Montréal (CHUM), Montreal, Québec, Canada.

Computed tomography (CT) and magnetic resonance imaging (MRI) play critical roles for assessing treatment response of hepatocellular carcinoma (HCC) after locoregional therapy. Interpretation is challenging because posttreatment imaging findings depend on the type of treatment, magnitude of treatment response, time interval after treatment, and other factors. To help radiologists interpret and report treatment response in a clear, simple, and standardized manner, the Liver Imaging Reporting and Data System (LI-RADS) has developed a Treatment Response (LR-TR) algorithm. Introduced in 2017, the system provides criteria to categorize response of HCC to locoregional treatment (e.g., chemical ablation, energy-based ablation, transcatheter therapy, and radiation therapy). LR-TR categories include Nonevaluable, Nonviable, Equivocal, and Viable. LR-TR does not apply to patients on systemic therapies. This article reviews the LR-TR algorithm; discusses locoregional therapies for HCC, treatment concepts, and expected posttreatment findings; and illustrates LI-RADS treatment response assessment with CT and MRI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13244-019-0801-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920285PMC
December 2019

Magnetic resonance imaging of obesity and metabolic disorders: Summary from the 2019 ISMRM Workshop.

Magn Reson Med 2020 05 29;83(5):1565-1576. Epub 2019 Nov 29.

Singapore Institute for Clinical Sciences, Agency for Science Technology and Research, Singapore.

More than 100 attendees from Australia, Austria, Belgium, Canada, China, Germany, Hong Kong, Indonesia, Japan, Malaysia, the Netherlands, the Philippines, Republic of Korea, Singapore, Sweden, Switzerland, the United Kingdom, and the United States convened in Singapore for the 2019 ISMRM-sponsored workshop on MRI of Obesity and Metabolic Disorders. The scientific program brought together a multidisciplinary group of researchers, trainees, and clinicians and included sessions in diabetes and insulin resistance; an update on recent advances in water-fat MRI acquisition and reconstruction methods; with applications in skeletal muscle, bone marrow, and adipose tissue quantification; a summary of recent findings in brown adipose tissue; new developments in imaging fat in the fetus, placenta, and neonates; the utility of liver elastography in obesity studies; and the emerging role of radiomics in population-based "big data" studies. The workshop featured keynote presentations on nutrition, epidemiology, genetics, and exercise physiology. Forty-four proffered scientific abstracts were also presented, covering the topics of brown adipose tissue, quantitative liver analysis from multiparametric data, disease prevalence and population health, technical and methodological developments in data acquisition and reconstruction, newfound applications of machine learning and neural networks, standardization of proton density fat fraction measurements, and X-nuclei applications. The purpose of this article is to summarize the scientific highlights from the workshop and identify future directions of work.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mrm.28103DOI Listing
May 2020

Gene Therapy for Liver Cancers: Current Status from Basic to Clinics.

Cancers (Basel) 2019 11 25;11(12). Epub 2019 Nov 25.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757, Aasahimachi-Dori, Chuo-Ku, Niigata, 9518510, Japan.

The liver is a key organ for metabolism, protein synthesis, detoxification, and endocrine function, and among liver diseases, including hepatitis, cirrhosis, malignant tumors, and congenital disease, liver cancer is one of the leading causes of cancer-related deaths worldwide. Conventional therapeutic options such as embolization and chemotherapy are not effective against advanced-stage liver cancer; therefore, continuous efforts focus on the development of novel therapeutic options, including molecular targeted agents and gene therapy. In this review, we will summarize the progress toward the development of gene therapies for liver cancer, with an emphasis on recent clinical trials and preclinical studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers11121865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966544PMC
November 2019

Deep Learning Convolutional Neural Networks for the Estimation of Liver Fibrosis Severity from Ultrasound Texture.

Proc SPIE Int Soc Opt Eng 2019 Feb 13;10950. Epub 2019 Mar 13.

University of Texas Southwestern Medical Center, Dallas, TX.

Diagnosis and staging of liver fibrosis is a vital prognostic marker in chronic liver diseases. Due to the inaccuracies and risk of complications associated with liver core needle biopsy, the current standard for diagnosis, other less invasive methods are sought for diagnosis. One such method that has been shown to correlate well with liver fibrosis is shear wave velocity measured by ultrasound (US) shear wave elastography; however, this technique requires specific software, hardware, and training. A current perspective in the radiology community is that the texture pattern from an US image may be predictive of the stage of liver fibrosis. We propose the use of convolutional neural networks (CNNs), a framework shown to be well suited for real world image interpretation, to test whether the texture pattern in gray scale elastography images (B-mode US with fixed, subject-agnostic acquisition settings) is predictive of the shear wave velocity (SWV). In this study, gray scale elastography images from over 300 patients including 3,500 images with corresponding SWV measurements were preprocessed and used as input to 100 different CNN architectures that were trained to regress shear wave velocity. In this study, even the best performing CNN explained only negligible variation in the shear wave velocity measures. These extensive test results suggest that the gray scale elastography image texture provides little predictive information about shear wave velocity and liver fibrosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1117/12.2512592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6859455PMC
February 2019

Pelvic muscle size and myosteatosis: Relationship with age, gender, and obesity.

Indian J Radiol Imaging 2019 Apr-Jun;29(2):155-162

Radiology, UT Southwestern Medical Center, Dallas, TX, USA.

Purpose: To evaluate interreader performance in the measurement of the cross-sectional area and myosteatosis of pelvic skeletal muscles using fat quantification magnetic resonance imaging (MRI) and correlate with patient anthropomorphic characteristics.

Materials And Methods: A Health Insurance Portability and Accountability Act-compliant retrospective cross-sectional study was performed. Between January and April 2016, 61 patients (26 males and 35 females) underwent a lumbosacral plexus 3T MRI with a modified three-dimensional spoiled gradient echo sequence dedicated to fat quantification (mDixon Quant; Philips Healthcare). Two independent reviewers outlined muscle cross-sectional area on axial images using a freehand region of interest tool and documented proton-density fat fraction (FF) and muscle area (cm) of the psoas, gluteus medius, gluteus maximus, and rectus femoris muscles on each side. Interreader agreement was assessed by intraclass correlation coefficient (ICC), and correlation between the measurements and subject's age, gender, and body mass index (BMI) was assessed using multiple linear regression analysis.

Results: Excellent interreader agreement was obtained (ICC ≥0.74) for all muscle groups except for the left gluteus medius area and right psoas FF which showed good agreement (0.65 and 0.61, respectively). Statistically significant ( ≤ 0.05) positive correlation was seen between the gluteal muscle FF and area with BMI, and rectus muscle FF with age and BMI. Statistically significant negative correlation between the rectus femoris area and age was also observed.

Conclusion: Fat quantification MRI is a highly reproducible imaging technique for the assessment of myosteatosis and muscle size. Intramuscular FF and cross-sectional area were correlated with age and BMI across multiple muscle groups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/ijri.IJRI_414_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6639865PMC
August 2019
-->