Rafael Duran

How I do it: a practical database management system to assist clinical research teams with data collection, organization, and reporting.

RATIONALE AND OBJECTIVES The objective of this study was to demonstrate that an intra-arterial liver therapy clinical research database system is a more workflow efficient and robust tool for clinical research than a spreadsheet storage system. The database system could be used to generate clinical research study populations easily with custom search and retrieval criteria. MATERIALS AND METHODS A questionnaire was designed and distributed to 21 board-certified radiologists to assess current data storage problems and clinician reception to a database management system. Based on the questionnaire findings, a customized database and user interface system were created to perform automatic calculations of clinical scores including staging systems such as the Child-Pugh and Barcelona Clinic Liver Cancer, and facilitates data input and output. RESULTS Questionnaire participants were favorable to a database system. The interface retrieved study-relevant data accurately and effectively. The database effectively produced easy-to-read study-specific patient populations with custom-defined inclusion/exclusion criteria. CONCLUSIONS The database management system is workflow efficient and robust in retrieving, storing, and analyzing data.

Radiologic-Pathologic Analysis of Contrast-enhanced and Diffusion-weighted MR Imaging in Patients with HCC after TACE: Diagnostic Accuracy of 3D Quantitative Image Analysis

PURPOSE To evaluate the diagnostic performance of three-dimensional ( 3D three-dimensional ) quantitative enhancement-based and diffusion-weighted volumetric magnetic resonance (MR) imaging assessment of hepatocellular carcinoma ( HCC hepatocellular carcinoma ) lesions in determining the extent of pathologic tumor necrosis after transarterial chemoembolization ( TACE transarterial chemoembolization ). MATERIALS AND METHODS This institutional review board-approved retrospective study included 17 patients with HCC hepatocellular carcinoma who underwent TACE transarterial chemoembolization before surgery. Semiautomatic 3D three-dimensional volumetric segmentation of target lesions was performed at the last MR examination before orthotopic liver transplantation or surgical resection. The amount of necrotic tumor tissue on contrast material-enhanced arterial phase MR images and the amount of diffusion-restricted tumor tissue on apparent diffusion coefficient ( ADC apparent diffusion coefficient ) maps were expressed as a percentage of the total tumor volume. Visual assessment of the extent of tumor necrosis and tumor response according to European Association for the Study of the Liver ( EASL European Association for the Study of the Liver ) criteria was performed. Pathologic tumor necrosis was quantified by using slide-by-slide segmentation. Correlation analysis was performed to evaluate the predictive values of the radiologic techniques. RESULTS At histopathologic examination, the mean percentage of tumor necrosis was 70% (range, 10%-100%). Both 3D three-dimensional quantitative techniques demonstrated a strong correlation with tumor necrosis at pathologic examination (R(2) = 0.9657 and R(2) = 0.9662 for quantitative EASL European Association for the Study of the Liver and quantitative ADC apparent diffusion coefficient , respectively) and a strong intermethod agreement (R(2) = 0.9585). Both methods showed a significantly lower discrepancy with pathologically measured necrosis (residual standard error [ RSE residual standard error ] = 6.38 and 6.33 for quantitative EASL European Association for the Study of the Liver and quantitative ADC apparent diffusion coefficient , respectively), when compared with non- 3D three-dimensional techniques ( RSE residual standard error = 12.18 for visual assessment). CONCLUSION This radiologic-pathologic correlation study demonstrates the diagnostic accuracy of 3D three-dimensional quantitative MR imaging techniques in identifying pathologically measured tumor necrosis in HCC hepatocellular carcinoma lesions treated with TACE transarterial chemoembolization .

Comparison of Existing Response Criteria in Patients with Hepatocellular Carcinoma Treated with Transarterial Chemoembolization Using a 3D Quantitative Approach

PURPOSE To compare currently available non-three-dimensional methods (Response Evaluation Criteria in Solid Tumors [RECIST], European Association for Study of the Liver [EASL], modified RECIST [mRECIST[) with three-dimensional (3D) quantitative methods of the index tumor as early response markers in predicting patient survival after initial transcatheter arterial chemoembolization (TACE). MATERIALS AND METHODS This was a retrospective single-institution HIPAA-compliant and institutional review board-approved study. From November 2001 to November 2008, 491 consecutive patients underwent intraarterial therapy for liver cancer with either conventional TACE or TACE with drug-eluting beads. A diagnosis of hepatocellular carcinoma (HCC) was made in 290 of these patients. The response of the index tumor on pre- and post-TACE magnetic resonance images was assessed retrospectively in 78 treatment-naïve patients with HCC (63 male; mean age, 63 years ± 11 [standard deviation]). Each response assessment method (RECIST, mRECIST, EASL, and 3D methods of volumetric RECIST [vRECIST] and quantitative EASL [qEASL]) was used to classify patients as responders or nonresponders by following standard guidelines for the uni- and bidimensional measurements and by using the formula for a sphere for the 3D measurements. The Kaplan-Meier method with the log-rank test was performed for each method to evaluate its ability to help predict survival of responders and nonresponders. Uni- and multivariate Cox proportional hazard ratio models were used to identify covariates that had significant association with survival. RESULTS The uni- and bidimensional measurements of RECIST (hazard ratio, 0.6; 95% confidence interval [CI]: 0.3, 1.0; P = .09), mRECIST (hazard ratio, 0.6; 95% CI: 0.6, 1.0; P = .05), and EASL (hazard ratio, 1.1; 95% CI: 0.6, 2.2; P = .75) did not show a significant difference in survival between responders and nonresponders, whereas vRECIST (hazard ratio, 0.6; 95% CI: 0.3, 1.0; P = .04), qEASL (Vol) (hazard ratio, 0.5; 95% CI: 0.3, 0.9; P = .02), and qEASL (%) (hazard ratio, 0.3; 95% CI: 0.15, 0.60; P < .001) did show a significant difference between these groups. CONCLUSION The 3D-based imaging biomarkers qEASL and vRECIST were tumor response criteria that could be used to predict patient survival early after initial TACE and enabled clear identification of nonresponders.

A Novel Inherently Radiopaque Bead for Transarterial Embolization to Treat Liver Cancer - A Pre-clinical Study

Purpose: Embolotherapy using microshperes is currently performed with soluble contrast to aid in visualization. However, administered payload visibility dimishes soon after delivery due to soluble contrast washout, leaving the radiolucent beads location unknown. The objective of our study was to characterize inherently radiopaque beads (RO Beads) in terms of physicomechanical properties, deliverability and imaging visibility in a rabbit VX2 liver tumor model. Materials and Methods: RO Beads, which are based on LC Bead® platform, were compared to LC Bead. Bead size (light microscopy), equilibrium water content (EWC), density, X-ray attenuation and iodine distribution (micro-CT), suspension (settling times), deliverability and in vitro penetration were investigated. Fifteen rabbits were embolized with either LC Bead or RO Beads + soluble contrast (iodixanol-320), or RO Beads+dextrose. Appearance was evaluated with fluoroscopy, X-ray single shot, cone-beam CT (CBCT). Results: Both bead types had a similar size distribution. RO Beads had lower EWC (60-72%) and higher density (1.21-1.36 g/cc) with a homogeneous iodine distribution within the beads interior. RO Beads suspension time was shorter than LC Bead, with durable suspension (>5 min) in 100% iodixanol. RO Beads ≤300 µm were deliverable through a 2.3-Fr microcatheter. Both bead types showed similar penetration. Soluble contrast could identify target and non-target embolization on fluoroscopy during administration. However, the imaging appearance vanished quickly for LC Bead as contrast washed-out. RO Beads+contrast significantly increased visibility on X-ray single shot compared to LC Bead+contrast in target and non-target arteries (P=0.0043). Similarly, RO beads demonstrated better visibility on CBCT in target arteries (P=0.0238) with a trend in non-target arteries (P=0.0519). RO Beads+dextrose were not sufficiently visible to monitor embolization using fluoroscopy. Conclusion: RO Beads provide better conspicuity to determine target and non-target embolization compared to LC Bead which may improve intra-procedural monitoring and post-procedural evaluation of transarterial embolization.

Uveal Melanoma Metastatic to the Liver: The Role of Quantitative Volumetric Contrast-Enhanced MR Imaging in the Assessment of Early Tumor Response after Transarterial Chemoembolization

PURPOSE To determine whether volumetric changes of enhancement as seen on contrast-enhanced magnetic resonance (MR) imaging can help assess early tumor response and predict survival in patients with metastatic uveal melanoma after one session of transarterial chemoembolization (TACE). MATERIALS AND METHODS Fifteen patients with 59 lesions who underwent MR imaging before and 3 to 4 weeks after the first TACE were retrospectively included. MR analysis evaluated signal intensities, World Health Organization (WHO), Response Evaluation Criteria in Solid Tumors (RECIST), European Association for the Study of the Liver (EASL), modified RECIST (mRECIST), tumor volume [volumetric RECIST (vRECIST)], and volumetric tumor enhancement [quantitative EASL (qEASL)]. qEASL was expressed in cubic centimeters [qEASL (cm3)] and as a percentage of the tumor volume [qEASL (%)]. Paired t test with its exact permutation distribution was used to compare measurements before and after TACE. The Kaplan-Meier method with the log-rank test was used to calculate overall survival for responders and non-responders. RESULTS In target lesions, mean qEASL (%) decreased from 63.9% to 42.6% (P = .016). No significant changes were observed using the other response criteria. In non-target lesions, mean WHO, RECIST, EASL, mRECIST, vRECIST, and qEASL (cm3) were significantly increased compared to baseline. qEASL (%) remained stable (P = .214). Median overall survival was 5.6 months. qEASL (cm3) was the only parameter that could predict survival based on target lesions (3.6 vs 40.5 months, P < .001) or overall (target and non-target lesions) response (4.4 vs 40.9 months, P = .001). CONCLUSION Volumetric tumor enhancement may be used as a surrogate biomarker for survival prediction in patients with uveal melanoma after the first TACE.

Three-dimensional Evaluation of Lipiodol Retention in HCC after Chemoembolization: A Quantitative Comparison between CBCT and MDCT

RATIONALE AND OBJECTIVES To evaluate the capability of cone-beam computed tomography (CBCT) acquired immediately after transcatheter arterial chemoembolization (TACE) in determining lipiodol retention quantitatively and volumetrically when compared to 1-day postprocedure unenhanced multidetector computed tomography (MDCT). MATERIALS AND METHODS From June to December 2012, 15 patients met the inclusion criteria of unresectable hepatocellular carcinoma (HCC) that was treated with conventional TACE (cTACE) and had intraprocedural CBCT and 1-day post-TACE MDCT. Four patients were excluded because the lipiodol was diffuse throughout the entire liver or lipiodol deposition was not clear on both CBCT and MDCT. Eleven patients with a total of 31 target lesions were included in the analysis. A quantitative three-dimensional software was used to assess complete, localized, and diffuse lipiodol deposition. Tumor volume, lipiodol volume in the tumor, percent lipiodol retention, and lipiodol enhancement in Hounsfield units (HU) were calculated and compared between CBCT and MDCT using two-tailed Students t test and Bland-Altman plots. RESULTS The mean value of tumor volume, lipiodol-deposited regions, calculated average percent lipiodol retention, and HU value of CBCT were not significantly different from those of MDCT (tumor volume: 9.37 ± 11.35 cm(3) vs 9.34 ± 11.44 cm(3), P = .991; lipiodol volume: 7.84 ± 9.34 cm(3) vs 7.84 ± 9.60 cm(3), P = .998; lipiodol retention: 89.3% ± 14.7% vs. 90.2% ± 14.9%, P = .811; HU value: 307.7 ± 160.1 HU vs. 257.2 ± 120.0 HU, P = .139). Bland-Altman plots showed only minimal difference and high agreement when comparing CBCT to MDCT. CONCLUSIONS CBCT has a similar capability, intraprocedurally, to assess lipiodol deposition in three dimensions for patients with HCC treated with cTACE when compared to MDCT.

Multidetector CT Features of Mesenteric Vein Thrombosis

Mesenteric vein thrombosis (MVT) accounts for 5%-15% of all mesenteric ischemic events and is classified as either primary or secondary. Primary MVT is idiopathic, whereas secondary MVT can result from a variety of underlying diseases and risk factors, including primary hypercoagulable states or prothrombotic disorders, myeloproliferative neoplasms, cancer (most frequently of the pancreas or liver), diverse inflammatory conditions, recent surgery, portal hypertension, and miscellaneous causes such as oral contraceptives or pregnancy. Clinical symptoms of MVT are rather nonspecific and are mainly characterized by abdominal pain. The mortality rate for MVT remains high, since even now the diagnosis is often delayed. Multidetector computed tomography (CT) is the modality of choice in this context. Although venous bowel ischemia occurs only infrequently with MVT, radiologists should be familiar with its multidetector CT features. Familiarity with the possible causes of MVT, the underlying pathogenic mechanisms associated with MVT, and the correlation between multidetector CT features and these pathogenic mechanisms is necessary to optimize medical management and improve patient care.

Systemic Delivery of Microencapsulated 3-Bromopyruvate for the Therapy of Pancreatic Cancer

Purpose: This study characterized the therapeutic efficacy of a systemically administered formulation of 3-bromopyruvate (3-BrPA), microencapsulated in a complex with β-cyclodextrin (β-CD), using an orthotopic xenograft mouse model of pancreatic ductal adenocarcinoma (PDAC). Experimental Design: The presence of the β-CD–3-BrPA complex was confirmed using nuclear magnetic resonance spectroscopy. Monolayer as well as three-dimensional organotypic cell culture was used to determine the half-maximal inhibitory concentrations (IC50) of β-CD–3-BrPA, free 3-BrPA, β-CD (control), and gemcitabine in MiaPaCa-2 and Suit-2 cell lines, both in normoxia and hypoxia. Phase-contrast microscopy, bioluminescence imaging (BLI), as well as zymography and Matrigel assays were used to characterize the effects of the drug in vitro. An orthotopic lucMiaPaCa-2 xenograft tumor model was used to investigate the in vivo efficacy. Results: β-CD–3-BrPA and free 3-BrPA demonstrated an almost identical IC50 profile in both PDAC cell lines with higher sensitivity in hypoxia. Using the Matrigel invasion assay as well as zymography, 3-BrPA showed anti-invasive effects in sublethal drug concentrations. In vivo, animals treated with β-CD–3-BrPA demonstrated minimal or no tumor progression as evident by the BLI signal as opposed to animals treated with gemcitabine or the β-CD (60-fold and 140-fold signal increase, respectively). In contrast to animals treated with free 3-BrPA, no lethal toxicity was observed for β-CD–3-BrPA. Conclusion: The microencapsulation of 3-BrPA represents a promising step towards achieving the goal of systemically deliverable antiglycolytic tumor therapy. The strong anticancer effects of β-CD–3-BrPA combined with its favorable toxicity profile suggest that clinical trials, particularly in patients with PDAC, should be considered. Clin Cancer Res; 20(24); 6406–17. ©2014 AACR.

Liver and biliary damages following transarterial chemoembolization of hepatocellular carcinoma: comparison between drug-eluting beads and lipiodol emulsion

ObjectivesTo compare transarterial chemoembolization (TACE)-related hepatic toxicities of conventional TACE (cTACE) and drug-eluting beads TACE (DEB-TACE) in patients with intermediate-stage hepatocellular carcinoma.MethodsIn this retrospective study, 151 consecutive patients undergoing cTACE or DEB-TACE and MRI 3-6 weeks before and after therapy were included. Toxicity was assessed on imaging (global hepatic damages (GHD), overall biliary injuries, biliary cast, bile duct dilatation, intrahepatic biloma, portal thrombosis), and clinico-biological follow-ups. Tumour response, time to progression (TTP), and overall survival were assessed. Factors influencing complication rate were identified by generalized equation logistic regression model.ResultsBiliary injuries and intrahepatic biloma incidence were significantly higher following DEB-TACE (p < 0.001). DEB-TACE showed a significant increased risk of GHD (OR: 3.13 [1.74-5.63], p < 0.001) and biliary injuries (OR: 4.53 [2.37-8.67], p < 0.001). A significant relationship was found between baseline prothrombin value and GHD, biliary injuries and intrahepatic biloma (all p < 0.01), and between the dose of chemotherapy and intrahepatic biloma (p = 0.001). Only TTP was significantly shorter following DEB-TACE compared to cTACE (p = 0.025).ConclusionsDEB-TACE was associated with increased hepatic toxicities compared to cTACE. GHD, biliary injuries, and intrahepatic biloma were more frequently observed with high baseline prothrombin value, suggesting that cTACE might be more appropriate than DEB-TACE in patients with less advanced cirrhosis.Key points• DEB-TACE demonstrated more therapy-related hepatic locoregional complications compared to cTACE.• TACE-related hepatic locoregional toxicities occurred more frequently with high baseline PT value.• cTACE may be more appropriate in patients with high baseline PT value.

Assessing tumor response after loco-regional liver cancer therapies: the role of 3D MRI

Assessing the tumor response of liver cancer lesions after intraarterial therapies is of major clinical interest. Over the last two decades, tumor response criteria have come a long way from purely size-based, anatomic methods such as the Response Evaluation Criteria in Solid Tumors towards more functional, enhancement- and diffusion-based parameters with a strong emphasis on MRI as the ultimate imaging modality. However, the relatively low reproducibility of those one- and 2D techniques (modified Response Evaluation Criteria in Solid Tumors and the European Association for the Study of the Liver criteria) provided the rationale for the development of new, 3D quantitative assessment techniques. This review will summarize and compare the existing methodologies used for 3D quantitative tumor analysis and provide an overview of the published clinical evidence for the benefits of 3D quantitative tumor response assessment techniques.