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Background: Bile acids mediate gut-liver cross-talk through bile acid receptors. Serum, hepatic, and microbial bile acid metabolism was evaluated in HCV-compensated chronic liver disease., Methods: Patients underwent liver biopsy; portal and peripheral blood were obtained before (HCVi), and 6 months after sustained virologic response (SVR), splenic blood was obtained only after SVR. The fecal microbiome and liver transcriptome were evaluated using RNA-Seq. Twenty-four bile acids were measured in serum, summed as free, taurine-conjugated bile acids (Tau-BAs), and glycine-conjugated bile acids., Results: Compared to SVR, HCVi showed elevated conjugated bile acids, predominantly Tau-BA, compounded in HCVi cirrhosis. In the liver, transcription of bile acids uptake, synthesis, and conjugation was decreased with increased hepatic spillover into systemic circulation in HCVi. There was no difference in the transcription of microbial bile acid metabolizing genes in HCVi. Despite an overall decrease, Tau-BA remained elevated in SVR cirrhosis, mainly in splenic circulation. Only conjugated bile acids, predominantly Tau-BA, correlated with serum proinflammatory markers and hepatic proinflammatory pathways, including NLRP3 and NFKB. Among hepatic bile acid receptors, disease-associated conjugated bile acids showed the strongest association with hepatic spingosine-1-phosphate receptor 2 (S1PR2)., Conclusions: Enhanced expression of hepatic S1PR2 in HCVi and HCVi-cirrhosis and strong associations of S1PR2 with Tau-BAs suggest pathological relevance of Tau-BA-hepatic S1PR2 signaling in chronic liver disease. These findings have therapeutic implications in chronic liver diseases.

Introduction: Perturbations in aromatic (AAAs) and branched-chain amino acids (BCAAs) are seen in decompensated liver disease. The aim of this study was to evaluate the dynamic, postprandial relationship between hepatitis C virus-induced liver disease and amino acid concentrations in patients with compensated liver disease., Methods: Patients infected with hepatitis C virus underwent a baseline liver biopsy to determine Ishak Fibrosis Score and evaluate the liver transcriptome. Patients ate a standard meal and underwent peripheral vein sampling at defined intervals. Quantitative analysis of amino acids was performed using liquid chromatography-tandem mass spectrometry., Results: At baseline, there was no difference in AAA and BCAA concentrations between patients with cirrhosis and non-cirrhotic patients. After a standard meal, AAAs, but not BCAAs, were elevated in patients with cirrhosis compared with non-cirrhotic patients at every time point. The HepQuant SHUNT fraction was significantly higher in patients with cirrhosis and positively correlated with AAA concentration at all time points, but not BCAA. Analysis of the hepatic transcriptome demonstrated greater downregulation of the AAA degradation pathways than the BCAA degradation pathways., Discussion: At baseline, cirrhotic patients with compensated liver disease have adequate reserve liver function to metabolize AAAs and BCAAs. When faced with a metabolic stressor, such as a standard meal, patients with cirrhosis are less able to metabolize the increased load of AAAs. This impairment correlates with portosystemic shunting. Further evaluation of AAA levels in compensated liver disease might further the understanding of the liver-muscle axis and the role it may play in the development of sarcopenia in liver disease., (Copyright © 2024 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Background: Current standard of care for advanced biliary tract cancer (BTC) is gemcitabine, cisplatin plus anti-PD1/PD-L1, but response rates are modest. The purpose of this study was to explore the efficacy and safety of durvalumab (anti-PD-L1) and tremelimumab (anti-CTLA-4), with and without an interventional radiology (IR) procedure in advanced BTC., Methods: Eligible patients with advanced BTC who had received or refused at least one prior line of systemic therapy were treated with tremelimumab and durvalumab for four combined doses followed by monthly durvalumab alone with and without an IR procedure until the progression of disease or unacceptable toxicity. Objective response was assessed through CT or MRI by Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) every 8 weeks. Adverse events (AEs) were recorded and managed. The primary endpoint was 6-month progression-free survival (PFS)., Results: Twenty-three patients with advanced BTC were enrolled; 17 patients were assigned to treatment with durvalumab and tremelimumab (Durva/Treme); and 6 patients were treated with the combination of durvalumab, tremelimumab plus IR procedure (Durva/Treme + IR). The best clinical responses in the Durva/Treme arm were partial response (n = 1), stable disease (n = 5), progressive disease (n = 5), and in the Durva/Treme + IR arm: partial response (n = 0), stable disease (n = 3), progressive disease (n = 3). The median PFS was 2.2 months (95% CI: 1.3-3.1 months) in the Durva/Treme arm and 2.9 months (95% CI: 1.9-4.7 months) in the Durva/Treme + IR arm (p = 0.27). The median OS was 5.1 months (95% CI: 2.5-6.9 months) in the Durva/Treme arm and 5.8 months (95% CI: 2.9-40.1 months) in the Durva/Treme + IR arm (p = 0.31). The majority of AEs were grades 1-2., Conclusion: Durva/Treme and Durva/Treme + IR showed similar efficacy. With a manageable safety profile. Larger studies are needed to fully characterize the efficacy of Durva/Treme ± IR in advanced BTC., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Microsatellite stable colorectal liver metastases (MSS CLM) maintain an immunosuppressive tumor microenvironment (TME). Historically, immune-based approaches have been ineffective. VB-111 (ofranergene obadenovec) is a genetically-modified adenoviral vector targeting the TME; its unique dual mechanism induces an immune response and disrupts neovascularization. Checkpoint inhibition may synergize the immune response induced by viral-mediated anti-angiogenic gene therapy. We aimed to examine the safety and antitumor activity of VB-111 and nivolumab in patients with refractory MSS CLM and to characterize immunological treatment-response., Methods: This was a phase II study of adult patients with histologically-confirmed MSS CLM who progressed on prior therapy. A priming dose of VB-111 1×10 13 viral particles was given intravenously 2 weeks prior to starting biweekly nivolumab 240 mg and continued every 6 weeks. The combination continued until disease progression or unacceptable toxicity. The primary objectives were overall response rate and safety/tolerability. Secondary objectives included median overall survival and progression-free survival. Correlative studies were performed on paired tumor biopsies and blood., Results: Between August 2020 and December 2021, 14 patients were enrolled with median age 50.5 years (40-75), and 14% were women. Median follow-up was 5.5 months. Of the 10 evaluable patients, the combination of VB-111 and nivolumab failed to demonstrate radiographic responses; at best, 2 patients had stable disease. Median overall survival was 5.5 months (95% CI: 2.3 to 10.8), and median progression-free survival was 1.8 months (95% CI: 1.4 to 1.9). The most common grade 3-4 treatment-related adverse events were fever/chills, influenza-like symptoms, and lymphopenia. No treatment-related deaths were reported. Qualitative analysis of immunohistochemical staining of paired tumor biopsies did not demonstrate significant immune infiltration after treatment, except for one patient who had exceptional survival (26.0 months). Immune analysis of peripheral blood mononuclear cells showed an increase of PD-1 high Ki67 high CD8 + T cells and HLA-DR high T cells after VB-111 priming dose. Plasma cytokines interleukin-10 and tumor necrosis factor-α increased after treatment with both drugs., Conclusion: In patients with MSS CLM, VB-111 and nivolumab did not improve overall response rate or survival but were tolerated with minimal toxicities. While challenging to distinguish between antiviral or antitumor, correlative studies demonstrated an immune response with activation and proliferation of CD8 + T cells systemically that was poorly sustained., Trial Registration Number: NCT04166383., Competing Interests: Competing interests: No, there are no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Cell-free RNAs (cfRNAs) are promising analytes as non-invasive biomarkers and have even greater potential if tied in with metabolomics. Plasma is an optimal source for cfRNAs but is often derived from a variety of anticoagulants. Plasma obtained in heparin is suitable for metabolomics but is difficult to utilize for qPCR-based downstream analysis. In the present study, we aimed to develop a simple, time-efficient, and cost-effective heparinase protocol, followed by library preparation and sequencing of human plasma cfRNAs drawn and stored in heparin at -80 °C for several years. Blood was collected in CPT™ sodium heparin tubes from patients with chronic HCV infection (NCT02400216) at the National Institutes of Health (NIH) Clinical Center. Plasma cfRNAs were treated with heparinase I and used for library preparation and next-generation sequencing (NGS). Heparinase treatment maintained RNA integrity and allowed for successful library preparation for all the study subjects even with 7 ng of cfRNAs as starting material. The classification report derived from Pavian R package v1.2.0 showed no artificial reads. The abundance of chordate over microbial reads suggests no addition of experimental error through heparinase I treatment. We report a novel and practical approach to heparinase treatment for human plasma collected and frozen in sodium heparin for several years. This is an effective demonstration of utilizing heparin plasma for NGS and downstream transcriptomic research, which could then be integrated with metabolomics from the same samples, maximizing efficiency and minimizing blood draws.

Background: Oncolytic immunotherapy represents a unique therapeutic platform for the treatment of cancer. Here, we evaluated the safety and efficacy of the combination of pexastimogene devacirepvec (PexaVec) plus durvalumab (anti-programmed death ligand 1) with and without tremelimumab (anti-cytotoxic T-lymphocyte associated protein 4) in patients with standard chemotherapy refractory mismatch repair proficient (pMMR) metastatic colorectal cancer (mCRC) in a phase I/II trial., Methods: Adult patients with histologically confirmed advanced pMMR mCRC, who had progressed on at least two prior lines of systemic chemotherapy were studied in four cohorts. Patients received four doses of PexaVec IV at a dose of 3×10 8 plaque forming units (pfu) (dose level 1) or 1×10 9  pfu (dose level 2) every 2 weeks. Twelve days after the first PexaVec administration, patients received either 1500 mg of durvalumab every 28 days alone or an additional single dose of 300 mg tremelimumab on day 1. Responses were assessed every 8 weeks by CT or MRI. AEs were recorded. The primary endpoints were safety and feasibility. Secondary endpoints included progression-free survival (PFS) and overall survival. Paired tumor samples and peripheral blood were collected to perform immune monitoring., Results: Thirty-four patients with mCRC enrolled on to the study: 16 patients in the PexaVec/durvalumab cohorts and 18 patients in the PexaVec/durvalumab/tremelimumab cohorts. Overall, the combination of PexaVec plus immune checkpoint inhibitors did not result in any unexpected toxicities. Most common toxicities observed were fever and chills after PexaVec infusion. Two cases of grade 3 colitis, one case of a grade 2 myositis and one case of grade 3 hypotension resulted in discontinuation of immune checkpoint inhibitor and PexaVec treatment, respectively. The median PFS in the PexaVec/durvalumab/tremelimumab cohorts was 2.3 months (95% CI: 2.2 to 3.2 months) vs 2.1 months (95% CI: 1.7 to 2.8 months; p=0.57) in the PexaVec/durvalumab cohorts. Flow cytometry analysis of peripheral blood mononuclear cells revealed an increase in Ki67 + CD8 + T cells on treatment., Conclusion: PexaVec in combination with durvalumab and tremelimumab is safe and tolerable. No unexpected toxicities were observed. The combination of PexaVec/durvalumab/tremelimumab demonstrated potential clinical activity in patients with pMMR mCRC, but further studies are needed to identify the predictive biomarkers., Trial Registration Number: NCT03206073., Competing Interests: Competing interests: AD reports participation of Advisory Boards from AstraZeneca, outside the submitted work. All other authors have nothing to disclose., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The gut and liver are connected via the portal vein, and this relationship, which includes the gut microbiome, is described as the gut-liver axis. Hepatitis C virus (HCV) can infect the liver and cause fibrosis with chronic infection. HCV has been associated with an altered gut microbiome; however, how these changes impact metabolism across the gut-liver axis and how this varies with disease severity and time is unclear. Here we used multi-omics analysis of portal and peripheral blood, faeces and liver tissue to characterize the gut-liver axis of patients with HCV across a fibrosis severity gradient before (n = 29) and 6 months after (n = 23) sustained virologic response, that is, no detection of the virus. Fatty acids were the major metabolites perturbed across the liver, portal vein and gut microbiome in HCV, especially in patients with cirrhosis. Decreased fatty acid degradation by hepatic peroxisomes and mitochondria was coupled with increased free fatty acid (FFA) influx to the liver via the portal vein. Metatranscriptomics indicated that Anaerostipes hadrus-mediated fatty acid synthesis influences portal FFAs. Both microbial fatty acid synthesis and portal FFAs were associated with enhanced hepatic fibrosis. Bacteroides vulgatus-mediated intestinal glycan breakdown was linked to portal glycan products, which in turn correlated with enhanced portal inflammation in HCV. Paired comparison of patient samples at both timepoints showed that hepatic metabolism, especially in peroxisomes, is persistently dysregulated in cirrhosis independently of the virus. Sustained virologic response was associated with a potential beneficial role for Methanobrevibacter smithii, which correlated with liver disease severity markers. These results develop our understanding of the gut-liver axis in HCV and non-HCV liver disease aetiologies and provide a foundation for future therapies., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objectives: The aims of this study were to develop a model to estimate drug dose delivered to tumors after transarterial chemoembolization (TACE) with radiopaque drug-eluting beads (DEBs) based on DEB density on cone-beam computed tomography (CT) and to evaluate drug penetration into tissue in a woodchuck hepatoma model., Materials and Methods: Transarterial chemoembolization was performed in woodchucks with hepatocellular carcinoma (N = 5) using DEBs (70-150 μm, LC Bead LUMI) loaded with doxorubicin. Livers were resected 45 minutes after embolization, immediately frozen, and cut using liver-specific, 3D-printed sectioning molds. Doxorubicin levels in tumor specimens were measured by high-performance liquid chromatography and correlated with DEB iodine content that was measured using prototype cone-beam CT-based embolization treatment planning software. Doxorubicin penetration into tissue surrounding DEBs was assessed by fluorescence microscopy of tumor sections. Fluorescence intensity was converted into doxorubicin concentration using calibration standards. Intensity-thresholded color heatmaps were generated representing extravascular drug penetration., Results: Consistent segmentation of DEBs on cone-beam CT was achieved using a semiautomated intensity thresholding method. A positive linear correlation (0.96) was found between DEB iodine content measured on cone-beam CT and the amount of doxorubicin measured in tumor specimens. Prediction of doxorubicin levels in tumor sections that were not included in model development was accurate, with a root-mean-square error of 0.08 mg of doxorubicin. Tumor penetration of eluted doxorubicin resulted in concentration gradients where drug content decreased with increasing distance from blood vessels containing DEBs. Drug penetration was greater for blood vessels containing DEB clusters compared with single DEB, with higher doxorubicin concentrations extending further away from the vessels., Conclusions: Estimation of drug dose delivered during transarterial chemoembolization in a woodchuck hepatocellular carcinoma model was possible using DEB radiopacity on cone-beam CT as a surrogate marker. Doxorubicin penetration was greatest adjacent to vessels containing DEB clusters compared with single DEB. Intraprocedural estimation of the spatial distribution of drug dose within the tumor could enable real-time adjustments to DEB delivery, to maximize treatment coverage or identify regions of tumor at risk for undertreatment., Competing Interests: Conflicts of interest and sources of funding: This work was supported by the Center for Interventional Oncology in the Intramural Research Program of the National Institutes of Health (NIH) by intramural NIH grants NIH Z01 1ZID BC011242 and CL040015. M.M.-H. is supported by the Clinical Translational Fellowship Program of the NIH Clinical Center and the Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering. The NIH has a Materials Transfer Agreement with Northeastern Wildlife. The NIH has Cooperative Research and Development Agreements with Biocompatibles UK Ltd–Boston Scientific Corporation and Philips that provide support for this research. The NIH had control over the conduct of the study, the inclusion of any data, data analysis and interpretation, manuscript preparation, and decisions on submission for publication. The content of this manuscript does not necessarily reflect the views or policies of the US Department of Health and Human Services. The mention of commercial products, their source, or their use in connection with material reported herein is not to be construed as an actual or implied endorsement of such products by the US government. W.v.d.S. is an employee of Philips. A.L.L. was an employee of Biocompatibles UK Ltd, the company sponsoring the study. B.J.W. is the principal investigator for Cooperative Research & Development Agreements between NIH and the following: BTG Biocompatibles/Boston Scientific, Siemens, Philips, NVIDIA, Celsion Corp, Canon Medical, and XAct Robotics. B.J.W. and NIH are party to Material Transfer or Collaboration Agreements with Angiodynamics, 3T Technologies, Profound Medical, Exact Imaging, Johnson and Johnson, Endocare/Healthtronics, and Medtronic. Outside the submitted work, B.J.W. is primary inventor on 47 issued patents owned by the NIH (list available upon request), a portion of which have been licensed by NIH to Philips. B.J.W. and NIH report a licensing agreement with Canon Medical on algorithm software with no patent. B.J.W. is joint inventor (assigned to the Department of Health and Human Services NIH US government) for patents and pending patents related to drug-eluting bead technology, some of which have joint inventorships with BTG Biocompatibles/Boston Scientific. B.J.W. is primary inventor on patents owned by NIH in the space of drug-eluting embolic beads. The authors report no other conflicts of interest in this work. This manuscript discusses the use of an investigational device, software for iodine quantification in Emboguide, a Philips product., (Copyright © 2022 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Adrenocortical carcinoma (ACC) is a rare malignancy with an overall unfavorable prognosis. Clinicians treating patients with ACC have noted accelerated growth in metastatic liver lesions that requires rapid intervention compared to other metastatic locations. This study measured and compared the growth rates of metastatic ACC lesions in the lungs, liver, and lymph nodes using volumetric segmentation. A total of 12 patients with metastatic ACC (six male; six female) were selected based on their medical history. Computer tomography (CT) exams were retrospectively reviewed and a sampling of ≤5 metastatic lesions per organ were selected for evaluation. Lesions in the liver, lung, and lymph nodes were measured and evaluated by volumetric segmentation. Statistical analyses were performed to compare the volumetric growth rates of the lesions in each organ system. In this cohort, 5/12 had liver lesions, 7/12 had lung lesions, and 5/12 had lymph node lesions. A total of 92 lesions were evaluated and segmented for lesion volumetry. The volume doubling time per organ system was 27 days in the liver, 90 days in the lungs, and 95 days in the lymph nodes. In this series of 12 patients with metastatic ACC, liver lesions showed a faster growth rate than lung or lymph node lesions.

Background: To evaluate outcomes and survival rates in patients with metastatic adrenocortical carcinoma (ACC) who were treated with image-guided locoregional treatments (IGLTs)., Purpose: To evaluate the overall survival (OS) and clinical impact of IGLT in the management of patients with advanced metastatic ACC., Methods: Retrospective review of 39 patients treated with IGLT between 1999 and 2018 was performed. Short- and long-term efficacy of treatments were defined based upon imaging and clinical data. Subgroup survival analysis was performed on patients with metastatic disease at diagnosis (N = 17) and compared with the same stage group from the most recent National Cancer Database (NCDB) report. Statistical analysis was performed using Cox proportional hazards model., Results: Treatments were performed at different anatomic sites including liver (N = 46), lung (N = 14), retroperitoneum (N = 5), bone (N = 4), subcutaneous (N = 2), and intracaval (N = 1). Radiofrequency, microwave, cryoablation, or a combination of two modalities (45, 18, 3, 3, respectively) were used in 69 ablation sessions. Intra-arterial procedures were performed in 12 patients in 18 treatment cycles (range 1-3 per patient). As of a 2019 analysis, 11 patients were alive with a mean follow-up of 169 months (range 63-292 months) from diagnosis. Two- and 5-year OS rates for all patients were 84.5% and 51%, respectively, and 76.5% and 59% for patients with metastatic disease at diagnosis (N = 17). This compares favorably with an NCDB report of 35% 5-year survival rate for patients with metastatic disease. Female gender and longer time from diagnosis to first IGLT were found to be predictors of prolonged survival with hazard ratios of 0.23 (p < 0.001) and 0.66 (p = 0.001), respectively., Conclusion: IGLT may be associated with prolonged life expectancy in select patients with metastatic ACC., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: Topotecan is a camptothecin analogue with potential advantages over irinotecan for transarterial chemoembolization (TACE) of hepatic colorectal metastases including greater anti-neoplastic activity without enzymatic activation. The purpose of this study was to assess safety and tolerability of topotecan-loaded radiopaque microspheres (ROMTOP) administered by TACE in a rabbit model and to compare the in vitro elution of topotecan from microspheres to irinotecan., Materials and Methods: Topotecan was loaded into radiopaque microspheres (70-150 µm, DC Bead LUMI™, Biocompatibles UK Ltd-Boston Scientific Corporation) to the maximum capacity of 80 mg/mL of microspheres. Six healthy New Zealand White rabbits underwent hepatic TACE with ROMTOP under fluoroscopic guidance until angiographic stasis. Assessment of toxicities included regular liver function tests and complete blood counts until euthanasia 28 days post-TACE. In vitro topotecan elution from the microspheres was assessed using an open-loop flow-through system and compared to irinotecan., Results: The mean bead volume and topotecan dose delivered were 0.086 mL (0.076-0.105 mL) and 1.99 mg/kg (1.51-2.55 mg/kg), respectively. Aspartate aminotransferase and alanine aminotransferase were elevated post-embolization but resolved within 2 weeks. One rabbit died two days after TACE with pyloric duodenal perforation observed at necropsy, potentially due to non-target embolization. In vitro elution of topotecan from ROMTOP was complete in 10 h compared to 3 h for irinotecan-loaded microspheres., Conclusion: Selective embolization with ROMTOP was tolerated at a dose of 2 mg/kg (24 mg/m 2 ) in rabbits. In vitro topotecan elution from microspheres was more prolonged compared to irinotecan.

Purpose: National Cancer Institute (NCI)-sponsored clinical trial network studies frequently require biopsy specimens for pharmacodynamic and molecular biomarker analyses, including paired pre- and post-treatment samples. The purpose of this meeting of NCI-sponsored investigators was to identify local institutional standard procedures found to ensure quantitative and qualitative specimen adequacy., Methods: NCI convened a conference on best biopsy practices, focusing on the clinical research community. Topics discussed were (1) criteria for specimen adequacy in the personalized medicine era, (2) team-based approaches to ensure specimen adequacy and quality control, and (3) risk considerations relevant to academic and community practitioners and their patients., Results and Recommendations: Key recommendations from the convened consensus panel included (1) establishment of infrastructure for multidisciplinary biopsy teams with a formalized information capture process, (2) maintenance of standard operating procedures with regular team review, (3) optimization of tissue collection and yield methodology, (4) incorporation of needle aspiration and other newer techniques, and (5) commitment of stakeholders to use of guideline documents to increase awareness of best biopsy practices, with the goal of universally improving tumor biopsy practices.

Vibration controlled transient elastography (VCTE) is validated for the evaluation of hepatic fibrosis in different liver diseases. Sickle cell liver disease (SCLD) results from a cumulative hepatic injury and its lifelong and progressive nature raises the need for a non-invasive tool for fibrosis evaluation. Fifty patients, aged between 23 and 59 years with sickle cell disease and suspected SCLD underwent a VCTE followed by a liver biopsy. Biopsies were evaluated for various scores of liver disease that were then correlated to VCTE score. 90% of our patients had an Ishak Fibrosis (IF) score between 0-2 (Group A-minimal to no fibrosis) and 10% of the patients had IF score between 3-6 (Group B-advanced fibrosis). The median Transient Elastography (TE) for patients in Groups A and B was 4·8 kilopascals (kPa) and 17·6 kPa, respectively. A positive correlation was shown between TE and IF score, R = 0·0·68 (P = <0·0001); a positive correlation was also shown with Histology Activity Index fibrosis score, R = 0·64 (P = <0·0001). This study emphasises the need for further studies of non-invasive tools and their utility in liver fibrosis evaluation of patients with SCLD., (Published 2019. This article is a U.S. Government work and is in the public domain in the USA.)

According to Barcelona Clinic Liver Cancer (BCLC) guidelines, interventional radiology procedures are valuable treatment options for many hepatocellular carcinomas (HCCs) that are not amenable to resection or transplantation. Accurate assessment of the efficacy of therapies at earlier stages enables completion of treatment, optimal follow-up and to prevent potentially unnecessary treatments, side effects and costly failure. The goal of this review is to summarize and describe the radiological strategies that have been proposed to predict survival and to stratify HCC responses after interventional radiology therapies. New techniques currently in development are also described.

Differences in drug metabolism associated with UGT1A1 polymorphism could result in individualized local response to hepatic chemoembolization with irinotecan-eluting beads (DEBIRI) or predictable toxicities. Five patients with inoperable hepatic metastases from colorectal or anal malignancies treated with DEBIRI were assessed for UGT1A1 mutations. No difference in area under the curve (AUC) for SN38 in normal liver and tumor tissue samples was noted with variant or wild-type UBT1A1 (P = .16 and P = .05, respectively). Plasma SN-38 AUC was significantly lower in wild-type compared to variant patients (P < .0001). UGT1A1 genotype may not be predictive of hematologic toxicity after DEBIRI., (Published by Elsevier Inc.)

Purpose To correlate bead location and attenuation on CT images with the quantity and distribution of drug delivered to the liver following transarterial chemoembolization (TACE) with radiopaque drug-eluting beads (DEB) in a rabbit tumor model. Materials and Methods All procedures were performed with a protocol approved by the Institutional Animal Care and Use Committee. TACE was performed in rabbits (n = 4) bearing VX2 liver tumors by using radiopaque DEB (70-150 µm) loaded with doxorubicin (DOX). Livers were resected 1 hour after embolization, immediately frozen, and cut by using liver-specific three-dimensional-printed molds for colocalization of liver specimens and CT imaging. DOX penetration into tissue surrounding beads was evaluated with fluorescence microscopy. DOX levels in liver specimens were predicted by using statistical models correlating DOX content measured in tissue with bead volume and attenuation measured on CT images. Model predictions were then compared with actual measured DOX concentrations to assess the models' predictive power. Results Eluted DOX remained in close proximity (<600 µm) to beads in the liver 1 hour after TACE. Bead volume and attenuation measured on CT images demonstrated positive linear correlations (0.950 and 0.965, respectively) with DOX content in liver specimens. DOX content model predictions based on CT images were accurate compared with actual liver DOX levels at 1 hour. Conclusion CT may be used to estimate drug dose delivery and distribution in the liver following transarterial chemoembolization (TACE) with doxorubicin-loaded radiopaque drug-eluting beads (DEB). Although speculative, this informational map might be helpful in planning and understanding the spatial effects of TACE with DEB. © RSNA, 2018.

This review describes the historical development of an imageable spherical embolic agent and focuses on work performed in collaboration between Biocompatibles UK Ltd (a BTG International group company) and the NIH to demonstrate radiopaque bead utility and bring a commercial offering to market that meets a clinical need. Various chemistries have been investigated and multiple prototypes evaluated in search of an optimized product with the right balance of handling and imaging properties. Herein, we describe the steps taken in the development of DC Bead LUMI™, the first commercially available radiopaque drug-eluting bead, ultimately leading to the first human experience of this novel embolic agent in the treatment of liver tumors.

Noncirrhotic portal hypertension (NCPH) is a rare disease that may lead to serious clinical consequences. Currently, noninvasive tools for the assessment of NCPH are absent. We investigated the utility of spleen and liver volumetrics as a marker of the presence and severity of portal hypertension in this population. A cohort of NCPH patients evaluated between 2003 and 2015 was retrospectively studied. The association of spleen and liver volumes with the hepatic venous pressure gradient (HVPG) level was evaluated using locally weighted scatterplot smoothing curves. A cohort of patients with viral hepatitis-related liver disease was used as controls. Of the 86 patients with NCPH evaluated during the study period, 75 (mean age, 35 ± 17; 73% males) were included in the final analysis. Patients with portal hypertension had significantly higher spleen and liver to body mass index (BMI) ratios compared to patients with HVPG <5 mm Hg (39.5 ± 27.9 versus 22.8 ± 10.6 cm 3 /kg/m 2 , P = 0.003; 91.1 ± 40.1 versus 71.4 ± 16.7 cm 3 /kg/m 2 , P = 0.014, for spleen/BMI and liver/BMI, respectively). In contrast to the patients with viral hepatitis, a positive linear correlation was observed in the NCPH cohort between spleen/BMI and liver/BMI (above a cutoff of 25 and 80 cm 3 /kg/m 2 , respectively) and HVPG level. Additionally, only in the NCPH cohort was an increase in spleen/BMI range quartile predictive of a higher prevalence of portal hypertension and clinically significant portal hypertension (trend, P = 0.014 and 0.031, respectively). Conclusion: Spleen and liver volumetrics may have utility in the assessment of NCPH as a noninvasive biomarker that can be performed using routine radiologic examinations. Further studies are needed to validate these findings. ( Hepatology Communications 2018; 00:000-000).

We have developed a straightforward and efficient method of introducing radiopacity into Polyvinyl alcohol (PVA)-2-Acrylamido-2-methylpropane sulfonic acid (AMPS) hydrogel beads (DC Bead™) that are currently used in the clinic to treat liver malignancies. Coupling of 2,3,5-triiodobenzaldehyde to the PVA backbone of pre-formed beads yields a uniformly distributed level of iodine attached throughout the bead structure (~150mg/mL) which is sufficient to be imaged under standard fluoroscopy and computed tomography (CT) imaging modalities used in treatment procedures (DC Bead LUMI™). Despite the chemical modification increasing the density of the beads to ~1.3g/cm 3 and the compressive modulus by two orders of magnitude, they remain easily suspended, handled and administered through standard microcatheters. As the core chemistry of DC Bead LUMI™ is the same as DC Bead™, it interacts with drugs using ion-exchange between sulfonic acid groups on the polymer and the positively charged amine groups of the drugs. Both doxorubicin (Dox) and irinotecan (Iri) elution kinetics for all bead sizes evaluated were within the parameters already investigated within the clinic for DC Bead™. Drug loading did not affect the radiopacity and there was a direct relationship between bead attenuation and Dox concentration. The ability (Dox)-loaded DC Bead LUMI™ to be visualized in vivo was demonstrated by the administration of into hepatic arteries of a VX2 tumor-bearing rabbit under fluoroscopy, followed by subsequent CT imaging., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: To describe first clinical experience with a directly image-able, inherently radio-opaque microspherical embolic agent for transarterial embolization of liver tumors., Methodology: LC Bead LUMI™ is a new product based upon sulfonate-modified polyvinyl alcohol hydrogel microbeads with covalently bound iodine (~260 mg I/ml). 70-150 μ LC Bead LUMI™ iodinated microbeads were injected selectively via a 2.8 Fr microcatheter to near complete flow stasis into hepatic arteries in three patients with hepatocellular carcinoma, carcinoid, or neuroendocrine tumor. A custom imaging platform tuned for LC LUMI™ microbead conspicuity using a cone beam CT (CBCT)/angiographic C-arm system (Allura Clarity FD20, Philips) was used along with CBCT embolization treatment planning software (EmboGuide, Philips)., Results: LC Bead LUMI™ image-able microbeads were easily delivered and monitored during the procedure using fluoroscopy, single-shot radiography (SSD), digital subtraction angiography (DSA), dual-phase enhanced and unenhanced CBCT, and unenhanced conventional CT obtained 48 h after the procedure. Intra-procedural imaging demonstrated tumor at risk for potential under-treatment, defined as paucity of image-able microbeads within a portion of the tumor which was confirmed at 48 h CT imaging. Fusion of pre- and post-embolization CBCT identified vessels without beads that corresponded to enhancing tumor tissue in the same location on follow-up imaging (48 h post)., Conclusion: LC Bead LUMI™ image-able microbeads provide real-time feedback and geographic localization of treatment in real time during treatment. The distribution and density of image-able beads within a tumor need further evaluation as an additional endpoint for embolization.

Purpose: To develop a simple method to produce radiopaque drug-eluting microspheres (drug-eluting beads [DEBs]) that could be incorporated into the current clinical transcatheter arterial chemoembolization workflow and evaluate their performance in vitro and in vivo., Materials and Methods: An ethiodized oil (Lipiodol; Guerbet, Villepinte, France) and ethanol solution was added to a lyophilized 100-300 µm bead before loading with doxorubicin. These radiopaque drug-eluting beads (DEBs; Biocompatibles UK Ltd, Farnham, United Kingdom) were evaluated in vitro for x-ray attenuation, composition, size, drug loading and elution, and correlation between attenuation and doxorubicin concentration. In vivo conspicuity was evaluated in a VX2 tumor model., Results: Lipiodol was loaded into lyophilized beads using two glass syringes and a three-way stopcock. Maximum bead attenuation was achieved within 30 minutes. X-ray attenuation of radiopaque beads increased linearly (21-867 HU) with the amount of beads (0.4-12.5 vol%; R(2) = 0.9989). Doxorubicin loading efficiency and total amount eluted were similar to DC Bead (Biocompatibles UK Ltd); however, the elution rate was slower for radiopaque DEBs (P < .05). Doxorubicin concentration linearly correlated with x-ray attenuation of radiopaque DEBs (R(2) = 0. 99). Radiopaque DEBs were seen in tumor feeding arteries after administration by fluoroscopy, computed tomography, and micro-computed tomography, and their location was confirmed by histology., Conclusions: A simple, rapid method to produce radiopaque DEBs was developed. These radiopaque DEBs provided sufficient conspicuity to be visualized with x-ray imaging techniques., (Copyright © 2016 SIR. All rights reserved.)

Purpose: To quantify changes in tumor microvascular (< 1 mm) perfusion relative to commonly used angiographic endpoints., Materials and Methods: Rabbit Vx2 liver tumors were embolized with 100-300-μm LC Bead particles to endpoints of substasis or complete stasis (controls were not embolized). Microvascular perfusion was evaluated by delivering two different fluorophore-conjugated perfusion markers (ie, lectins) through the catheter before embolization and 5 min after reaching the desired angiographic endpoint. Tumor microvasculature was labeled with an anti-CD31 antibody and analyzed with fluorescence microscopy for perfusion marker overlap/mismatch. Data were analyzed by analysis of variance and post hoc test (n = 3-5 per group; 18 total)., Results: Mean microvascular density was 70 vessels/mm(2) ± 17 (standard error of the mean), and 81% ± 1 of microvasculature (ie, CD31(+) structures) was functionally perfused within viable Vx2 tumor regions. Embolization to the extent of substasis eliminated perfusion in 37% ± 9 of perfused microvessels (P > .05 vs baseline), whereas embolization to the extent of angiographic stasis eliminated perfusion in 56% ± 8 of perfused microvessels. Persistent microvascular perfusion following embolization was predominantly found in the tumor periphery, adjacent to normal tissue. Newly perfused microvasculature was evident following embolization to substasis but not when embolization was performed to complete angiographic stasis., Conclusions: Nearly half of tumor microvasculature remained patent despite embolization to complete angiographic stasis. The observed preservation of tumor microvasculature perfusion with angiographic endpoints of substasis and stasis may have implications for tumor response to embolotherapy., (Published by Elsevier Inc.)

Purpose: To evaluate the effect of embolic diameter on achievement of hypoxia after embolization in an animal model of liver tumors., Materials and Methods: Inoculation of VX2 tumors in the left liver lobe was performed successfully in 12 New Zealand white rabbits weighing 3.7 kg ± 0.5 (mean ± SD). Tumors were deemed eligible for oxygen measurements when the maximum transverse diameter measured 15 mm or more by ultrasound examination. Direct monitoring of oxygenation of implanted rabbit hepatic VX2 tumors was performed with a fiberoptic electrode during and after transarterial embolization of the proper hepatic artery to angiographic flow stasis with microspheres measuring 70-150 μm, 100-300 μm, or 300-500 μm in diameter., Results: Failure to achieve tumor hypoxia as defined despite angiographic flow stasis was observed in 10 of 11 animals. Embolization microsphere size effect failed to demonstrate a significant trend on hypoxia outcome among the diameters tested, and pair-wise comparisons of different embolic diameter treatment groups showed no difference in hypoxia outcome. All microsphere diameters tested resulted in similar absolute reduction (24.3 mm Hg ± 18.3, 29.1 mm Hg ± 1.8, and 19.9 mm Hg ± 9.3, P = .66) and percentage decrease in oxygen (56.0 mm Hg ± 23.9, 56.0 mm Hg ± 6.4, and 35.8 mm Hg ± 20.6, P = .65). Pair-wise comparisons for percent tumor area occupied by embolic agents showed a significantly reduced fraction for 300-500 μm diameters compared with 70-150 μm diameters (P < .05)., Conclusions: In the rabbit VX2 liver tumor model, three tested microsphere diameters failed to cause tumor hypoxia as measured by a fiberoptic probe sensor according to the adopted hypoxia definitions., (Copyright © 2015. Published by Elsevier Inc.)

Background: Regional chemotherapy is used successfully in the treatment of both primary and secondary malignancies, in particular of the peritoneal surface and the liver, and is currently explored as an attractive approach for patients with locally advanced pancreatic ductal adenocarcinoma. To establish the feasibility and toxicity of regional intra-arterial gemcitabine delivered as a 24-h continuous infusion to the pancreas as a novel treatment option for patients with locally advanced PDAC a phase I clinical trial was conducted., Methods: Between April 2011 and September 2013 six patients with biopsy confirmed, borderline or unresectable pancreatic adenocarcinoma, and having received at least one line of systemic chemotherapy, underwent vascular redistribution of the inflow to the head of the pancreas by arterial coil embolization followed by perfusion catheter placement within the splenic artery. Patients were treated with increasing doses of gemcitabine administered by continuous splenic arterial infusion over 24 h with inter-patient and intra-patient dose escalation scheme. The primary endpoint was toxicity of the intra-arterial gemcitabine regimen and to establish the maximum tolerated dose., Results: Catheter placement and gemcitabine infusion was successful in all patients enrolled to date (n = 6). Four out of six patients experienced catheter tip migration requiring replacement or revision. Patients received a median of four doses of 24-h gemcitabine infusion. Two patients developed grade 3 and 4 duodenal ischemia and upper gastrointestinal bleeding. Median overall survival was 15.3 months and median time to progression was 3 months. Three patients (50 %, n = 3/6) progressed systemically. Two patients had stable disease >4 months following treatment and underwent pancreaticoduodenectomy., Conclusions: While technically feasible to treat locally advanced pancreatic ductal adenocarcinoma, prolonged regional pancreatic perfusion with gemcitabine following pancreatic arterial redistribution carries a high risk for gastrointestinal toxicity. Shorter infusion schedules with frequent on treatment evaluations should be considered for future clinical trials.

Purpose: To study the impact of race in an equal access care institution with a predominantly African-American (AA) population., Methods: We retrospectively reviewed data from 222 men with low risk (LR) or intermediate risk (IR) prostate cancer who underwent radical prostatectomy at the New York Harbor VA between 2003 and 2011. Biochemical relapse, distant control, and prostate cancer-specific survival were analyzed using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate Cox regression modeling was performed to determine the impact of covariates on biochemical outcome., Results: Most patients (65.3 %) were AA. The median follow-up was 58 months, and 89.6 % of patients were followed for a minimum of 2 years after their surgery. Analyzing the whole cohort, the biochemical control was improved in Caucasian patients compared with AA (90.2 vs. 75.4 %, p = 0.008). On subgroup analysis, for IR disease, this difference was no longer significant, 80.5 % for Caucasians versus 69.8 % for AA (p = 0.36). However, for LR disease, the 5-year biochemical control remained significantly improved for Caucasians compared with AA, with a 5-year biochemical control of 97.6 versus 81.7 %, p = 0.006. On multivariate analysis, AA race was a significant predictor for biochemical recurrence (HR 2.69, 95 % CI 1.27-5.65, p = 0.009). There were no differences between the two groups regarding distant control (p = 0.14) or prostate cancer-specific survival (p = 0.29)., Conclusions: In this predominant AA population with equal access to medical care, AA race is an independent predictor of biochemical recurrence after prostatectomy in men with LR or IR prostate cancer.

Purpose: To determine local doxorubicin levels surrounding radiopaque drug-eluting beads (DEBs) in normal swine liver and kidney following transcatheter arterial chemoembolization. The influence of bead size (70-150 μm or 100-300 μm) was compared with regard to tissue penetration and spatial distribution of the bead, as well as eventual drug coverage (ie, amount of tissue exposed to drug)., Materials and Methods: Radiopaque DEBs were synthesized by suspension polymerization followed by incorporation of iodized oil and doxorubicin. Chemoembolization of swine liver and kidney was performed under fluoroscopic guidance. Three-dimensional tissue penetration of "imageable" DEBs was investigated ex vivo with micro-computed tomography (microCT). Drug penetration from the bead surface and drug coverage was evaluated with epifluorescence microscopy, and cellular localization of doxorubicin was evaluated with confocal microscopy. Necrosis was evaluated with hematoxylin and eosin staining., Results: MicroCT demonstrated that 70-150-μm DEBs were present in more distal arteries and located in a more frequent and homogeneous spatial distribution. Tissue penetration of doxorubicin from the bead appeared similar (∼300 μm) for both DEBs, with a maximum tissue drug concentration at 1 hour coinciding with nuclear localization of doxorubicin. The greater spatial frequency of the 70-150-μm DEBs resulted in approximately twofold improved drug coverage in kidney. Cellular death is predominantly observed around the DEBs beginning at 8 hours, but increased at 24 and 168 hours., Conclusions: Smaller DEBs penetrated further into targeted tissue (ie, macroscopic) with a higher spatial density, resulting in greater and more uniform drug coverage (ie, microscopic) in swine., (Copyright © 2012 SIR. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess the feasibility of combined electromagnetic device tracking and computed tomography (CT)/ultrasonography (US)/fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) fusion for real-time feedback during percutaneous and intraoperative biopsies and hepatic radiofrequency (RF) ablation., Materials and Methods: In this HIPAA-compliant, institutional review board-approved prospective study with written informed consent, 25 patients (17 men, eight women) underwent 33 percutaneous and three intraoperative biopsies of 36 FDG-avid targets between November 2007 and August 2010. One patient underwent biopsy and RF ablation of an FDG-avid hepatic focus. Targets demonstrated heterogeneous FDG uptake or were not well seen or were totally inapparent at conventional imaging. Preprocedural FDG PET scans were rigidly registered through a semiautomatic method to intraprocedural CT scans. Coaxial biopsy needle introducer tips and RF ablation electrode guider needle tips containing electromagnetic sensor coils were spatially tracked through an electromagnetic field generator. Real-time US scans were registered through a fiducial-based method, allowing US scans to be fused with intraprocedural CT and preacquired FDG PET scans. A visual display of US/CT image fusion with overlaid coregistered FDG PET targets was used for guidance; navigation software enabled real-time biopsy needle and needle electrode navigation and feedback., Results: Successful fusion of real-time US to coregistered CT and FDG PET scans was achieved in all patients. Thirty-one of 36 biopsies were diagnostic (malignancy in 18 cases, benign processes in 13 cases). RF ablation resulted in resolution of targeted FDG avidity, with no local treatment failure during short follow-up (56 days)., Conclusion: Combined electromagnetic device tracking and image fusion with real-time feedback may facilitate biopsies and ablations of focal FDG PET abnormalities that would be challenging with conventional image guidance.

Transjugular liver biopsy is an essential procedure in the armamentarium of the interventional radiologist for patients who otherwise are unable to undergo percutaneous liver biopsy. Multiple conditions exist that necessitate the transjugular approach for biopsy, including acquired coagulopathy, congenital blood disorders, or requirement for measurements of hepatic venous and/or wedged hepatic vein pressures. The safety and efficacy of transjugular liver biopsy is well established, with many studies citing extremely low rates of complication with high rates of technical success. Nonetheless, transjugular liver biopsy is not without complications. The most often reported complication is asymptomatic capsular perforation; however occasionally, major hemorrhagic complications and even death have been reported. We describe two major hemorrhagic complications that manifested several days after the procedure and required emergent intervention.

Rationale and Objectives: Electromagnetic tracking potentially may be used to guide percutaneous needle-based interventional procedures. The accuracy of electromagnetic guided-needle puncture procedures has not been specifically characterized. This article reports the functional accuracy of a needle guidance system featuring real-time tracking of respiratory-related target motion., Materials and Methods: A needle puncture algorithm based on a "free-hand" needle puncture technique for percutaneous intrahepatic portocaval systemic shunt was employed. Preoperatively obtained computed tomographic images were displayed on a graphical user interface and registered with the electromagnetically tracked needle position. The system and procedure was tested on an abdominal torso phantom containing a liver model mounted on a motor-driven platform to simulate respiratory excursion. The liver model featured two hollow tubes to simulate intrahepatic vessels. Registration and respiratory motion tracking was performed using four skin fiducials and a needle fiducial within the liver. Success rates for 15 attempts at simultaneous puncture of the two "vessels" of different luminal diameters guided by the electromagnetic tracking system were recorded., Results: Successful "vessel" puncture occurred in 0%, 33%, and 53% of attempts for 3-, 5-, and 7-mm diameter "vessels," respectively. Using a two-dimensional accuracy prediction analysis, predicted accuracy exceeded actual puncture accuracy by 25%-35% for all vessel diameters. Accuracy outcome improved when depth-only errors were omitted from the analysis., Conclusions: Actual puncture success rate approximates predicted rates for target vessels 5 mm in diameter or greater when depth errors are excluded. Greater accuracy for smaller diameter vessels would be desirable for implementation in a broader range of clinical applications.

Electromagnetic tracking potentially may be used to guide percutaneous needle-based interventional procedures. This brief report describes our initial experience with an electromagnetic guidance system featuring real-time tracking of respiratory-related target motion using an internal fiducial. An algorithm based on a "freehand" needle puncture technique was employed to puncture the right portal vein and a right hepatic vein for percutaneous intrahepatic portosystemic shunt in a swine model. Preoperative computed tomographic images registered with the electromagnetically tracked needle position were displayed for guidance. Successful puncture was confirmed angiographically. Simultaneous percutaneous transhepatic puncture of the targeted veins was accomplished on the initial attempt.

Radiofrequency ablation of primary and metastatic liver tumors is becoming a potential alternative to surgical resection. We propose a novel system that uses real-time electromagnetic position sensing of the needle tip to help with precision guidance into a liver tumor. The purpose of this study was to evaluate this technology in phantom and animal models. Using an electromagnetic navigation device, instrumented 18 g needles were advanced into radioopaque tumor targets in a respiratory liver phantom. The phantom featured a moving liver target that simulated cranio-caudal liver motion due to respiration. Skin-to-target path planning and real-time needle guidance were provided by a custom-designed software interface based on pre-operative 1 mm CT data slices. Needle probes were advanced using only the electromagnetic navigation device and software display. No conventional real-time imaging was used to assist in advancing the needle to the target. Two experienced operators (interventional radiologists) and two inexperienced ones (residents) used the system. The same protocol was then also used in two anesthetized 45 kg Yorkshire swine where radioopaque agar nodules were injected into the liver to serve as targets. A total of 76 tumor targeting attempts were performed in the liver phantom, and 32 attempts were done in the swine. The average time for path planning was 30 s in the phantom, and 63 s in the swine. The median time for the actual needle puncture to reach the desired target was 33 s in the phantom, and 42 s in the swine. The average registration error between the CT coordinate system and electromagnetic coordinate system was 1.4 mm (SD 0.3 mm) in the phantom, and 1.9 mm (SD 0.4 mm) in the swine. The median distance from the final needle tip position to the center of the tumor was 6.4 mm (SD 3.3 mm, n=76) in the phantom, and 8.3 mm (SD 3.7 mm, n=32) in the swine. There was no statistical difference in the planning time, procedure time, or accuracy of needle placement between experienced and inexperienced operators. The novel electromagnetic navigation system allows probe delivery into hepatic tumors of a physiologic phantom and live anesthetized swine. The system allows less experienced operators to perform equally well as experienced radiologists in terms of procedure time and accuracy of needle probe delivery.

To categorize the anatomic variants of uterine arteries, and determine the incidence of menopausal symptoms where the tubo-ovarian branches were seen prior to embolization. Between July 1997 and June 2000, 257 (n = 257) uterine fibroid embolizations were performed at our institution. Arteriograms were retrospectively evaluated. Uterine arteries were classified into groups: type I (the uterine artery as first branch of the inferior gluteal artery), type II (the uterine artery as second or third branch of the inferior gluteal artery), type III (the uterine artery, the inferior gluteal and the superior gluteal arteries arising as a trifurcation), type IV (the uterine artery as first branch of the hypogastric artery), inconclusive, or not studied. Tubo-ovarian branches were recorded if visualized prior to and/or after embolization. Menopausal symptoms were recorded (n = 175 at 3 months, n = 139 at 6 months, n = 98 at 1 year, n = 22 at 2 years) using written questionnaires. Five hundred and fourteen uterine arteries (n = 514) were evaluated. There were 38% classifiable types, 23% inconclusive, and 39% not studied. Classification was as follows: type I, 45%; type II, 6%; type III, 43%; type IV, 6%. Among 256 patients, tubo-ovarian arteries were seen in 36 prior to embolization, but not afterwards. In this group, 25 patients reported transient menopausal symptoms (hot flashes, amenorrhea). Five patients did not report any menopausal symptoms. Six patients did not answer the questionnaires. Type I is the most common type of anatomy, followed by type III. The tubo-ovarian arteries may be visualized prior to and/or after embolization. The embolization was monitored to avoid embolization of the tubo-ovarian branches. Menopausal symptoms were transient all patients when the tubo-ovarian branches were seen prior to embolization.

Evaluation of the anatomic feasibility of the percutaneous transabdominal puncture of selected portal and hepatic veins in patients with cirrhosis was performed. This approach would become the framework for an image-guided robot-assisted needle drive mechanism for use in transjugular intrahepatic portosystemic shunt (TIPS) creation. Retrospective analysis of 10 CT and 14 MRI axial abdominal studies was carried out to determine whether single simultaneous transabdominal puncture of portal and hepatic veins was possible. A necessary modification of the TIPS procedure was tested in an ex vivo porcine model under fluoroscopy. Eighteen of 24 patients (75%) had intrahepatic vascular anatomy amenable to a single transabdominal puncture. Successful catheterization of portal and hepatic veins using a modified approach for TIPS was accomplished in two ex vivo porcine livers. A suitable anatomic approach for modified TIPS is present in a majority of patients with cirrhosis. Feasibility of the technique using this anatomic approach was confirmed in two ex vivo porcine models. This study serves as an initial step in a novel technical approach to TIPS using a new anatomic approach for this procedure.

Purpose: To determine whether baseline variables are associated with treatment success after uterine artery embolization for treatment of uterine leiomyoma., Materials and Methods: Two hundred consecutive patients who underwent uterine artery embolization at one institution were prospectively examined. Baseline clinical variables measured included age, race, prior oral contraceptive use or progesterone treatment, prior gonadotropin-releasing hormone agonist treatment, and prior births. Imaging parameters were baseline uterine volume, baseline leiomyoma volume and location, and number of leiomyomas. After treatment, follow-up imaging and questionnaire data were obtained at 3 and 12 months. Associations between baseline characteristics and outcome variables of interest were assessed by using linear regression, logistic regression, Pearson product moment correlation coefficients, and Kendal tau correlation coefficients, with adjustment for confounding variables when indicated., Results: Regression models indicated that larger dominant leiomyoma volume was associated with a smaller percentage reduction in volume at 3 months (P =.03). A submucosal leiomyoma location was associated with a greater volume reduction at 3 months (P =.04), but this difference did not persist at 12 months (P =.09). The odds of reported menstrual bleeding improvement at 3 months were higher with a submucosal leiomyoma location (P =.04); however, this association was not statistically significant after adjustment (P =.07). The odds of improved bulk-related symptoms were not associated with leiomyoma volume change or location., Conclusion: Smaller baseline leiomyoma size and submucosal location are more likely to result in a positive imaging outcome. There are limited associations between other baseline parameters and either symptom change or imaging outcome.

Purpose: To evaluate the effectiveness of intraarterial lidocaine in controlling pain after uterine artery embolization (UAE)., Materials and Methods: In this double-blind prospective study, patients undergoing UAE received preservative-free 1% lidocaine or saline solution (control) in the uterine arteries before embolization. Postprocedural pain was managed with patient-controlled intravenous morphine. Attempted doses, number of doses received, total morphine dose, and maximum pain numeric rating scale (NRS) score during the postprocedural hospitalization were recorded and compared. Three-month follow-up magnetic resonance (MR) imaging and symptomatic questionnaires were collected and compared., Results: Ten patients received lidocaine and eight patients received placebo. Moderate to severe vasospasm was noted in seven patients after lidocaine injection, whereas no vasospasm was noted in the placebo group (P =.004). Patients in the lidocaine group had lower NRS pain scores than those in the placebo group (P =.012), whereas there was no difference in morphine requirement between treated patients and control subjects. The study was terminated after 18 patients were treated as a result of unexpected vasospasm., Conclusions: Intraarterial 1% lidocaine is associated with moderate to severe vasospasm. Lidocaine significantly lowers subjective pain, but there is no difference in analgesic requirements. The routine use of intraarterial lidocaine is not recommended for pain control until the long-term effects of vasospasm on outcome is known.

Objective: To determine whether uterine artery embolization is safe and effective for treating uterine leiomyomata., Methods: We analyzed 200 consecutive patients (61 reported previously) undergoing uterine artery embolization for the treatment of uterine leiomyomata at a single institution. After treatment, follow-up data were obtained by written questionnaire mailed to the patients at intervals of 2 weeks, 3 months, 6 months, and 12 months after treatment. Follow-up imaging was obtained at 3 months and 12 months after therapy. All complications and subsequent gynecologic interventions were recorded prospectively, obtained using the patient questionnaires and physician contact. The percentages and their 95% confidence intervals (CI) were calculated to compare the symptoms at follow-up. Proportional odds models for repeated ordinal responses were used to assess the stability of symptom improvement over time., Results: The mean follow-up was 21 months (minimum 12). Heavy menstrual bleeding improved in 87% (95% CI 82%, 92%) of patients at 3 months and in 90% (95% CI 86%, 95%) at 1 year after therapy. Bulk symptoms improved in 93% of patients (95% CI 88%, 96%) at 3 months and in 91% (95% CI 86%, 95%) at 1 year after treatment. Only one major periprocedural complication occurred (pulmonary embolus), which resolved with anticoagulant therapy. Subsequent gynecologic interventions occurred in 10.5% of the patients (95% CI 7.0%, 15.0%) during the follow-up period., Conclusion: Uterine artery embolization is safe and controls the symptoms caused by leiomyomata in most patients.

Purpose: To determine whether the severity of postprocedure pain associated with uterine artery embolization (UAE) for leiomyomata can be predicted and if its severity can predict outcome., Materials and Methods: Eighty-one patients underwent UAE and had postprocedure pain managed with use of patient-controlled analgesia (PCA) in the form of an intravenous morphine pump. Baseline uterine and dominant fibroid volumes were calculated for each patient. Attempted doses, doses given, total morphine dose, and maximum numerical rating scale (NRS) score during postprocedure hospitalization were recorded. At 3 months postprocedure, repeat imaging was used to determine uterine and dominant fibroid volume reduction. Each patient also completed a questionnaire assessing change in menstrual bleeding, pelvic pain and pressure symptoms, and satisfaction with symptomatic outcome. Simple regression analysis was used to determine if baseline volumes predicted postprocedure pain and if the pain-related variables could be used to predict outcome., Results: Neither baseline uterine volume nor dominant fibroid volume predicted the severity of postprocedure pain. Similarly, none of the pain-related variables predicted uterine or fibroid volume reduction, symptomatic improvement, or satisfaction with outcome., Conclusions: Postprocedural pain cannot be predicted based on baseline uterine or fibroid volume and the severity of pain experienced cannot be used to predict outcome.

The sonographic appearance of the endometrium was evaluated in 97 infertile women, 51 from a fertility unit (FU) and 46 from an in vitro fertilization (IVF) program. Three groups of patients were identified: those with normal findings, those with an incomplete endometrial echo, and those without any endometrial echo. Findings were correlated with the type of ovulation induction protocol, the peak estradiol level, and the number of successful pregnancies. In the IVF group, 72% of the patients did not exhibit normal endometrial echoes but had adequate estradiol levels, compared with 62% of the FU patients with normal endometrial echoes but significantly lower estradiol. The data suggest that IVF patients have a nonresponsive endometrium rather than inadequate estrogen stimulation and therefore that an endometrial abnormality may be an important cause of their infertility. Ultrasound may be used as a screening method to identify such patients.