Variability in biopsy quality informs translational research applications in hepatocellular carcinoma.

In the era of precision medicine, biopsies are playing an increasingly central role in cancer research and treatment paradigms; however, patient outcomes and analyses of biopsy quality, as well as impact on downstream clinical and research applications, remain underreported. Herein, we report biopsy safety and quality outcomes for percutaneous core biopsies of hepatocellular carcinoma (HCC) performed as part of a prospective clinical trial. Patients with a clinical diagnosis of HCC were enrolled in a prospective cohort study for the genetic, proteomic, and metabolomic profiling of HCC at two academic medical centers from April 2016 to July 2020. Under image guidance, 18G core biopsies were obtained using coaxial technique at the time of locoregional therapy. The primary outcome was biopsy quality, defined as tumor fraction in the core biopsy. 56 HCC lesions from 50 patients underwent 60 biopsy events with a median of 8 core biopsies per procedure (interquartile range, IQR, 7-10). Malignancy was identified in 45/56 (80.4%, 4 without pathology) biopsy events, including HCC (40/56, 71.4%) and cholangiocarcinoma (CCA) or combined HCC-CCA (5/56, 8.9%). Biopsy quality was highly variable with a median of 40% tumor in each biopsy core (IQR 10-75). Only 43/56 (76.8%) and 23/56 (41.1%) samples met quality thresholds for genomic or metabolomic/proteomic profiling, respectively, requiring expansion of the clinical trial. Overall and major complication rates were 5/60 (8.3%) and 3/60 (5.0%), respectively. Despite uniform biopsy protocol, biopsy quality varied widely with up to 59% of samples to be inadequate for intended purpose. This finding has important consequences for clinical trial design and highlights the need for quality control prior to applications in which the presence of benign cell types may substantially alter findings.

Type 2 Endoleak Management.

Type 2 endoleaks are the most common endoleak type following endovascular aneurysm repair. The natural history of these endoleaks can vary, with some demonstrating a self-limited or indolent course, while others can contribute to aneurysm sac enlargement and rupture. A variety of embolization techniques, including transarterial catheterization and direct sac puncture techniques, have been developed for the treatment of type 2 endoleaks. In this article, the authors review the indications, techniques, and outcomes of current treatment strategies for type 2 endoleaks.

Establishment of hepatocellular carcinoma patient-derived xenografts from image-guided percutaneous biopsies.

While patient-derived xenograft (PDX) models of hepatocellular carcinoma (HCC) have been successfully generated from resected tissues, no reliable methods have been reported for the generation of PDXs from patients who are not candidates for resection and represent the vast majority of patients with HCC. Here we compare two methods for the creation of PDXs from HCC biopsies and find that implantation of whole biopsy samples without the addition of basement membrane matrix favors the formation of PDX tumors that resemble Epstein-Barr virus (EBV)-driven B-cell lymphomas rather than HCC tumors. In contrast, implantation with Matrigel supports growth of HCC cells and leads to a high rate of HCC tumor formation from these biopsies. We validate the resulting PDXs, confirm their fidelity to the patients' disease and conclude that minimally invasive percutaneous liver biopsies can be used with relatively high efficiency to generate PDXs of HCC.

Endovascular Therapy for Below-the-Elbow Arterial Disease: An Initial Single-Center Experience.

Purpose: To evaluate the technical success, clinical success, and complication rates of endovascular revascularization for below-the-elbow (BTE) peripheral artery disease. Materials and Methods: A retrospective review was performed of 19 patients (mean age 63 years; 12 men) with critical hand ischemia (CHI) who underwent 25 interventions in 19 arms between October 2010 and June 2017. Access was attained using 4-F or 5-F sheaths via antegrade brachial, retrograde radial, or fistula/graft access routes depending on the target vessel. A 0.018-inch hydrophilic microwire was used for intimal or subintimal recanalization. Angioplasty was performed over a 0.014-inch guidewire using low-profile balloons. The primary endpoint of the study was technical success, defined as successful lesion crossing/dilation, with residual stenosis <30%. Clinical success referred to improvement in pain and/or steal symptoms. Results: Technical success was achieved in 88% (22 of 25 procedures), with no significant difference in outcome associated with indications or baseline vessel disease. Complications occurred in 6 cases, of which 5 were minor and 1 was major. Clinical success was achieved in 12 of 14 patients with available follow-up; 5 of 7 patients with ulcers experienced wound healing. Conclusion: Endovascular revascularization for BTE occlusive disease is an effective and safe strategy for treating CHI.

Randomized Embolization Trial for NeuroEndocrine Tumor Metastases to the Liver (RETNET): study protocol for a randomized controlled trial.

BACKGROUND: Neuroendocrine tumors (NETs) are the second most common gastrointestinal malignancy after colon cancer. Up to 90% of patients with NETs develop liver metastases, which are a major determinant of symptoms and survival. Current guidelines recommend embolotherapy for progressive or symptomatic NET liver metastases, but the optimal technique among bland embolization, lipiodol chemoembolization, and drug-eluting bead chemoembolization remains unknown and controversial. METHODS/DESIGN: A prospective, open-label, multicenter randomized controlled trial will be conducted in patients with progressive or symptomatic unresectable NET liver metastases. Patients will be randomized to treatment with bland embolization, lipiodol chemoembolization, or drug-eluting microsphere chemoembolization, with 60 enrollees per arm. The primary endpoint will be hepatic progression-free survival (HPFS) following initial embolotherapy by RECIST criteria. The sample size is powered to detect an HR of 1.78 for HPFS following chemoembolization compared with bland embolization, which was estimated on the basis of existing retrospective studies. Secondary endpoints include overall progression-free survival, duration of symptom control, quality of life, rate of adverse events, and interval between embolotherapy cycles. Interim safety analyses will be performed at 10 and 30 patients per arm. DISCUSSION: The RETNET trial is a prospective, multicenter randomized controlled trial designed to determine the optimal embolotherapy technique for NET liver metastases. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02724540 . Registered on March 31, 2016.

Endobronchial Forceps-Assisted and Excimer Laser-Assisted Inferior Vena Cava Filter Removal: The Data, Where We Are, and How It Is Done.

The recognition of inferior vena cava filter related complications has motivated increased attentiveness in clinical follow-up of patients with inferior vena cava filters and has led to development of multiple approaches for retrieving filters that are challenging or impossible to remove using conventional techniques. Endobronchial forceps and excimer lasers are tools for designed to aid in complex inferior vena cava filter removals. This article discusses endobronchial forceps-assisted and excimer laser-assisted inferior vena cava filter retrievals.

A randomized comparison between an intravenous catheter system with a retractable guidewire and conventional intravenous catheters.

INTRODUCTION: The aim of this study is to compare an intravenous (IV) catheter system which uses a retractable guidewire (RG-IV) designed to facilitate IV placement with a conventional IV (C-IV) catheter control. MATERIALS AND METHODS: A prospective, randomized design was used. Patients referred to interventional radiology for outpatient procedures were offered participation. Enrollment occurred between August and November 2013. Patients were assigned to receive the RG-IV or C-IV in a 1:1 randomization scheme. After assignment, up to three attempts by a registered nurse occurred with the assigned device; if all three attempts failed, crossover to the other device occurred. The primary outcome variable was first-attempt success at IV placement. Secondary outcome variables included patient and clinician satisfaction, number of attempts, and time to successful placement. Two hundred twenty patients were enrolled (139 men, 81 women) in the study. RESULTS: Of the 220 patients, two were withdrawn prior to IV attempt leaving 218 subjects, 109 in each group. First attempt success (77% RG-IV vs. 82% C-IV, p = 0.5), number of attempts to achieve IV access (1.26 RG-IV vs. 1.29 C-IV, p = 0.98), and time to achieve IV success (2.9 minutes RG-IV vs. 2.7 C-IV, p = 0.82) did not differ between groups. Patient satisfaction with insertion was higher in the C-IV group (4.5/5 vs. 3.9/5, p<0.001) although comfort comparison was not (3.3/5 RG-IV vs. 3.5/5 C-IV, p = 0.15). CONCLUSIONS: In an interventional radiology outpatient population, the RG-IV and C-IV were comparable in first-attempt success, number of attempts, and time to achieve IV success. Patient satisfaction was higher with C-IV.

Embolotherapy for Neuroendocrine Tumor Liver Metastases: Prognostic Factors for Hepatic Progression-Free Survival and Overall Survival.

PURPOSE: The purpose of the study was to evaluate prognostic factors for survival outcomes following embolotherapy for neuroendocrine tumor (NET) liver metastases. MATERIALS AND METHODS: This was a multicenter retrospective study of 155 patients (60 years mean age, 57 % male) with NET liver metastases from pancreas (n = 71), gut (n = 68), lung (n = 8), or other/unknown (n = 8) primary sites treated with conventional transarterial chemoembolization (TACE, n = 50), transarterial radioembolization (TARE, n = 64), or transarterial embolization (TAE, n = 41) between 2004 and 2015. Patient-, tumor-, and treatment-related factors were evaluated for prognostic effect on hepatic progression-free survival (HPFS) and overall survival (OS) using unadjusted and propensity score-weighted univariate and multivariate Cox proportional hazards models. RESULTS: Median HPFS and OS were 18.5 and 125.1 months for G1 (n = 75), 12.2 and 33.9 months for G2 (n = 60), and 4.9 and 9.3 months for G3 tumors (n = 20), respectively (p < 0.05). Tumor burden >50 % hepatic volume demonstrated 5.5- and 26.8-month shorter median HPFS and OS, respectively, versus burden ≤50 % (p < 0.05). There were no significant differences in HPFS or OS between gut or pancreas primaries. In multivariate HPFS analysis, there were no significant differences among embolotherapy modalities. In multivariate OS analysis, TARE had a higher hazard ratio than TACE (unadjusted Cox model: HR 2.1, p = 0.02; propensity score adjusted model: HR 1.8, p = 0.11), while TAE did not differ significantly from TACE. CONCLUSION: Higher tumor grade and tumor burden prognosticated shorter HPFS and OS. TARE had a higher hazard ratio for OS than TACE. There were no significant differences in HPFS among embolotherapy modalities.

Role of Catheter-directed Thrombolysis in Management of Iliofemoral Deep Venous Thrombosis.

The treatment for iliofemoral deep venous thrombosis (DVT) is challenging, as the use of anticoagulation alone can be insufficient for restoring venous patency and thus lead to prolongation of acute symptoms and an increased risk of chronic complications, including venous insufficiency and postthrombotic syndrome (PTS). In these cases, earlier and more complete thrombus removal can ameliorate acute symptoms and reduce long-term sequelae. Endovascular therapies involving the use of pharmacologic, mechanical, and combined pharmacomechanical modalities have been developed to achieve these goals. The most frequently used of these techniques, catheter-directed thrombolysis (CDT), involves the infusion of a thrombolytic agent through a multiple-side-hole catheter placed within the thrombosed vein to achieve high local doses and thereby break down the clot while minimizing systemic thrombolytic agent exposure. Randomized controlled trial results have indicated decreased PTS rates and improved venous patency rates in patients treated with CDT compared with these rates in patients treated with anticoagulation. The use of newer pharmacomechanical techniques, as compared with conventional CDT, reduces procedural times and thrombolytic agent doses and is the subject of ongoing investigations. Endovascular thrombus removal techniques offer a means to improve venous valvular function and decrease the risk of debilitating long-term complications such as PTS and are a promising option for treating patients with iliofemoral DVT. (©)RSNA, 2016.

Analysis of the Final DENALI Trial Data: A Prospective, Multicenter Study of the Denali Inferior Vena Cava Filter.

PURPOSE: To report the final 2-year data on the efficacy and safety of a nitinol retrievable inferior vena cava (IVC) filter for protection against pulmonary embolism (PE). MATERIALS AND METHODS: This was a prospective multicenter trial of 200 patients with temporary indications for caval filtration who underwent implantation of the Denali IVC filter. After filter placement, all patients were followed for 2 years after placement or 30 days after filter retrieval. The primary endpoints were technical success of filter implantation in the intended location and clinical success of filter placement and retrieval. Secondary endpoints were incidence of clinically symptomatic recurrent PE, new or propagating deep vein thrombosis (DVT), and filter-related complications including migration, fracture, penetration, and tilt. RESULTS: Filter placement was technically successful in 199 patients (99.5%). Filters were clinically successful in 190 patients (95%). The rate of PE was 3% (n = 6), with 5 patients having a small subsegmental PE and 1 having a lobar PE. New or worsening DVT was noted in 26 patients (13%). Filter retrieval was attempted 125 times in 124 patients and was technically successful in 121 patients (97.6%). The mean filter dwell time at retrieval was 200.8 days (range, 5-736 d). There were no instances of filter fracture, migration, or tilt greater than 15° at the time of filter retrieval or during follow-up. CONCLUSIONS: The Denali IVC filter exhibited high success rates for filter placement and retrieval while maintaining a low complication rate in this clinical trial.

Tumor Growth Kinetics and Oncologic Outcomes of Patients Undergoing Active Surveillance for Residual Renal Tumor following Percutaneous Thermal Ablation.

PURPOSE: To evaluate growth kinetics and oncologic outcomes of patients with renal tumors undergoing active surveillance (AS) for residual viable tumor following percutaneous ablation. MATERIALS AND METHODS: Following percutaneous thermal ablation, residual tumor was detected in 21/133 (16%) patients on initial follow-up imaging, and AS was undertaken in 17/21 (81%) patients. Initial tumor volumes and volumes after ablation were assessed from cross-sectional imaging to calculate volumetric growth rate (VGR) and volume doubling time (VDT) of residual tumor. The rate of metastasis, overall survival, and renal cell carcinoma (RCC)-specific survival were compared between patients in the AS group and in the routine follow up group of patients who did not have residual tumor. RESULTS: Median tumor volume prior to ablation, after first ablation, and at final follow-up were 25 cm(3), 6 cm(3), and 6 cm(3), respectively, in patients with residual tumor. Stable, mild, and moderate VGR occurred in 8/17 (47%), 4/17 (24%), and 5/17 (29%) cases, respectively. The 4 cases with fastest VDT underwent delayed intervention with ablation (n = 1) and nephrectomy (n = 3) without subsequent residual, recurrence, or metastasis. There was no significant difference in the rates of RCC metastasis, overall survival, or RCC-specific survival between AS and routine follow-up groups. Metastatic RCC and subsequent death occurred in 1 patient in the AS group, after the patient had refused offers for retreatment for local progression over 60.7 months of follow-up. CONCLUSIONS: In cases when patients are not amenable to further intervention, AS of residual tumor may be an acceptable alternative and allows for successful delayed intervention when needed.

Complication and Readmission Rates following Same-Day Discharge after Percutaneous Renal Tumor Ablation.

PURPOSE: To evaluate readmission rate and complications in patients undergoing same-day discharge following percutaneous thermal ablation of renal tumors. MATERIALS AND METHODS: Patients undergoing same-day discharge following thermal ablation of renal tumors were reviewed. The primary outcome was the rate of readmission within 30 days of same-day discharge. The secondary outcomes included the rate and clinical outcomes of periprocedural complications. RESULTS: Same-day discharge occurred in 166/174 patients (95%), of whom 2/166 (1%) required short-term readmission due to pulmonary embolism and acute-on-chronic kidney injury. Both patients recovered without permanent morbidity. Admission due to complications occurred in 8/174 (5%) cases, the majority of which were related to hemorrhage. No significant differences in rates of complications or admission were found between cryoablation and RF ablation. Major complications (Clavien-Dindo grade II or higher, SIR grade C or higher) occurred in 7/174 (4%) cases, the majority related to hemorrhage. All cases were detected in the standard 4 hour postprocedural observation period and managed conservatively. The mean hemorrhage volume was significantly larger in patients requiring admission versus those discharged the same day (289 mL vs 34 mL; P = .02). Higher-volume hemorrhage occurred in larger tumors (mean, 4.0 cm vs 3.0 cm; P = .04). There was no association between major complications and central tumor or age. CONCLUSIONS: Routine same-day discharge following percutaneous renal tumor thermal ablation can be performed with a low rate of short-term readmission. The majority of periprocedural complications can be managed conservatively, and patients can be discharged the same day.

Angiographic detection and characterization of "cryptic venous anomalies" associated with spinal cord cavernous malformations using flat-panel catheter angiotomography.

BACKGROUND: Spinal cord cavernous malformations (CMs) are associated with 2 types of angiographically occult "cryptic venous anomalies," which differ in location with respect to the spinal cord. The anatomic distinction between superficial and intramedullary is important in that the latter heighten the risks of CM resection. OBJECTIVE: To report the observations of both types of cryptic venous anomalies documented during spinal digital subtraction angiography enhanced with flat-panel catheter angiotomography (FPCA). METHODS: Spinal digital subtraction angiography enhanced with FPCA was performed in 2 adult patients with magnetic resonance imaging--documented intramedullary spinal cord CMs and prominent, nonspecific flow voids at the same levels. FPCA was obtained by selective injection of left T4 (case 1) and left T9 (case 2) with 5F Cobra 2 catheters (Terumo, Japan) during a 20-second rotational acquisition. Thirty milliliters of a 75% saline and 25% contrast solution (Omnipaque 300; GE) was administered. The rotational data set was reconstructed on a dedicated workstation (Leonardo; Siemens, Erlangen, Germany) through the use of regular and high-resolution matrixes, 0.4- and 0.1-mm voxel size, respectively. RESULTS: Spinal digital subtraction angiography was unremarkable in both cases. In case 1, FPCA findings indicated an atypical network of prominent posterior perimedullary veins. In case 2, FPCA identified radially oriented channels forming a caput medusae pattern collecting into an enlarged intramedullary vein. CONCLUSION: The unique ability of FPCA to image the spinal venous system enables the angiographic detection and characterization of abnormal spinal veins associated with CMs. Differentiating between the types of associated cryptic venous malformations may aid in surgical planning because the intramedullary type is associated with a higher risk of surgical complication.

Undulating microcatheter tip motion with respiratory cycle during intracranial aneurysm embolization: description of a case and strategy for its mitigation.

The present report describes a technique for mitigating respiration-related microcatheter motion during endovascular aneurysm treatment by modulating ventilator settings. A rare phenomenon of microcatheter tip movement related to respiration is demonstrated. An adjustment of tidal volume and respiratory rate reduced the degree of inspiratory vessel elongation and stabilized the microcatheter position, allowing for safer, more precise coil deployment. This maneuver can easily be applied to other endovascular procedures for which aberrant microcatheter motion must be minimized.

Establishment of a human glioblastoma stemlike brainstem rodent tumor model.

OBJECT: Diffuse brainstem tumors are the most difficult type of pediatric CNS malignancy to treat. These inoperable lesions are treated with radiation alone or in combination with chemotherapy, and the survival rate is less than 10%. It is therefore essential to develop a reliable animal model to screen new therapeutic agents for the treatment of this type of tumor. METHODS: A multipotent human glioblastoma stemlike neurosphere line, 060919, was established from a surgically resected glioblastoma specimen; when cells were implanted intracranially into athymic nude mice, they formed invasive, vascular tumors that exhibited the features of glioblastoma. Ten female Fischer 344 rats received an injection of 75,000 F98 rat glioma cells and 10 female athymic nude rats received an injection of 75,000 060919 human glioblastoma stemlike cells in the pontine tegmentum of the brainstem. A control group of 5 female Fischer rats received an injection of saline in the same location as the animals in the tumor groups. Kaplan-Meier curves were generated for survival, and brains were processed postmortem for histopathological investigation. RESULTS: Both F98 cells and 060919 cells grew in 100% of the animals injected. Median survival of animals injected with F98 was 15 days, consistent with the authors' previous reports on the establishment of the brainstem tumor model using the F98 rat glioma line. Median survival of animals injected with 060919 was 31 days. Histopathological analysis of the tumors confirmed the presence of brainstem lesions in animals that received brainstem injections of F98 and in animals that received brainstem injections of 060919. The 060919 brainstem tumors histologically resembled glioblastoma. CONCLUSIONS: Tumor take and median survival were consistent for animals injected in the brainstem with either the established F98 rat glioma cell line or the 060919 human glioblastoma stemlike neurosphere line. Histopathological features of the 060919 brainstem tumors resembled glioblastoma. Establishment of this human glioblastoma stemlike brainstem animal model will improve the evaluation and identification of more efficacious agents for the treatment of high-grade brainstem tumors.

Preferential DNA damage and poor repair determine ras gene mutational hotspot in human cancer.

BACKGROUND: Mutations in ras genes are commonly found in human cancers and in animal models. Although mutations at codons 12, 13, and 61 of H-, N- and K-ras genes can activate their oncogenic function, mutations at codon 12 of K-ras are the most common mutations found among the three ras genes in human cancers. To investigate whether codon 12 of human K-ras is especially susceptible to carcinogens and/or whether carcinogen-DNA adducts at this codon are repaired less efficiently, we examined tobacco smoke carcinogen-induced DNA damage in normal human bronchial epithelial and fibroblast cells. METHODS: We used the UvrABC nuclease incision method in combination with ligation-mediated polymerase chain reaction to map the distribution of DNA adducts induced by benzo[a]pyrene diol epoxide (BPDE) and other bulky carcinogens within exons 1 and 2 in H-ras, N-ras, and K-ras. We also analyzed BPDE-DNA adduct repair efficiency in these three genes using the same method. RESULTS: Codons 12 and 14 of the K-ras gene were hotspots for carcinogen-DNA adduct formation, with little and no adduct formation at codons 13 and 61, respectively. The BPDE-DNA adducts formed at codon 14 were repaired almost twice as quickly as those formed at codon 12. There was some BPDE-DNA adduct formation at codons 12 of H-ras and N-ras, but this codon was not a hotspot. Furthermore, no substantial difference in repair rates between codon 12 and the other codons analyzed (codons 3 and 18) was observed in either the H-ras or N-ras genes. CONCLUSION: These findings link the human cancer mutational hotspot at codon 12 of K-ras to preferential DNA damage and poor repair.

Mapping polycyclic aromatic hydrocarbon and aromatic amine-induced DNA damage in cancer-related genes at the sequence level.

Genomic injury induced by environmental carcinogens, such as polycyclic aromatic hydrocarbons and aromatic amines, is the initial step that can trigger mutagenesis and carcinogenesis. In addition to the physico-chemical property of DNA damaging agents, several important factors such as primary sequence, chromatin structure, methylation, protein association, and transcriptional activity can affect not only the initial level and distribution of DNA damage but also the efficiency of repair. Therefore, mapping the DNA damage induced by environmental agents in cancer-related genes such as p53 and ras at the sequence level provides essential information for assessing their carcinogenic potential. Recently, using the E. coli nucleotide excision enzyme complex, UvrABC nucleases in combination with ligation-mediated polymerase chain reaction, we developed a method to map DNA damage in the p53 and ras genes. These studies led us to conclude that targeted DNA damage, in combination with growth selection, contributes greatly in shaping the mutation spectrum in these genes in human cancer. Here we present the rationale and details of this approach, typical experimental results and necessary precautions.