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 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.

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.

The generation of patient derived xenografts (PDXs) from core needle biopsies of intermediate and advanced stage HCC patients who are not candidates for resection is technically challenging due to the small quantities of tumor tissue obtained. Further complicating PDX generation is the high rate of EBV infection in humans (>90%) and the presence of EBV-transformed B lymphocytes in HCC samples, which grow opportunistically in immunocompromised mice to yield EBV-associated lymphomas at the expense of HCC xenografts. We sought to identify methodological improvements in PDX generation that mitigate the formation of lymphocytic PDXs and improve the efficiency of HCC-xenograftment. As part of an ongoing observational clinical trial of subjects with HCC, ultrasound-guided percutaneous biopsies were obtained from treatment-naïve patients. Entire biopsy samples were subcutaneously engrafted into immunodeficient mice using either basement membrane matrix (Matrigel) or PBS as an inoculation substrate. Tumor growth was monitored and mice were euthanized for necropsy when tumors reached a threshold size. Immunohistochemistry and in-situ hybridization (ISH) was done on explanted xenografts to examine the expression of immune cell (CD3, CD20, CD45), HCC/hepatocholangiocarcinoma (AFP, albumin, CK7, HNF4a), and EBV (EBV-encoded RNA; EBER1)-associated molecular markers. Xenografts arising from biopsies implanted without Matrigel uniformly expressed the immune cell marker CD45, whereas xenografts implanted with Matrigel did not (N=9 biopsies from 5 patients that resulted in xenograft). Further characterization with human-CD3/CD20 co-staining and ISH for EBER1 showed that these tumors were consistent with EBV driven B-cell lymphomas. Only in xenografts implanted with matrigel did we see expression of AFP, albumin, CK7, or HNF4a. These data suggest that minimally invasive percutaneous liver biopsies can be used with relatively high efficiency to generate patient derived xenografts for the two most common primary liver cancer subtypes and that this process may be augmented by the addition of Matrigel during the implantation process.

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.

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.

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.

The increasing accessibility and affordability of genome sequencing technologies have solidified the link between variations in the genetic code and human health. While pharmacologic targeting of the encoded proteins that are downstream effectors of genomic variation has been a mainstay, these recent advances in the understanding of the human genome underscore the power of genetic engineering for studying and treating disease. This recognition has led to the rapid development of tools for the direct modification of DNA through genome editing. The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9 system is the most recent addition to this toolset and holds great promise for clinical and research applications (Fig 1a, b).

Marked intertumoral genetic heterogeneity of hepatocellular carcinoma (HCC) poses a fundamental challenge to therapy development, as mutations found in existing immortalized tumor cell lines may not effectively recapitulate individual tumor profiles. The purpose of this study was to determine optimal methods for derivation and propagation of primary cell culture lines from HCC biopsy samples, as the foundation for a precision medicine approach to identifying targetable genetic vulnerabilities in HCC using clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 approach. Tumor samples were acquired by percutaneous core needle biopsy. A core was immediately processed for cell culture and another was frozen for DNA sequencing, to provide a baseline for evaluating genetic fidelity of propagated cell lines. Tissue cores were dissociated using combination of enzymatic and mechanical methods. HCC cells were enriched by lysis of red blood cells (RBC) and removal of endothelial cells. The robustness of cell propagation was evaluated using a 7-day growth curve assay. Variations in culture technique including the use of gelatin-coated vs. uncoated plates, and hepatocyte-specific (HMM) vs. generic (RPMI-1640) cell culture media were evaluated. Cells were transduced with a lentivirus vector containing CRISPR/Cas-9 components and transduction efficiency was assessed. RBC lysis and endothelial cell removal were effective for enriching the HCC cell population. Gelatin-coated plates supported 1/3 shorter cell adhesion times as compared to tissue culture plastic. Cells grown in generic media demonstrated a one-fold shorter doubling time compared to hepatocyte specific media. Cultured cells were able to be maintained for at least 6 passages. Lentiviral transduction of the CRISPR/Cas-9 vector was successful with transduction efficiency up to 95%. Primary cell culture can be effectively established and propagated from HCC core needle biopsy samples and transduced with a CRISPR/Cas-9 vector construct providing the potential for functional genome editing to enable precision medicine in HCC.

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.

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.

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 degrees 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.

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.

Intraductal papillary mucinous neoplasm (IPMN) is a cystic neoplasm of the pancreas characterized by dysplastic mucin-producing epithelial cells that arise from either the main pancreatic duct or its branches. IPMNs are more commonly seen in men 60–70 years old, with an estimated incidence of 4.3 per 100,000 persons ( 1 Klibansky D.A. Reid-Lombardo K.M. Gordon S.R. Gardner T.B. The clinical relevance of the increasing incidence of intraductal papillary mucinous neoplasm. Clin Gastroenterol Hepatol. 2012; 10: 555-558 Abstract Full Text Full Text PDF PubMed Scopus (108) Google Scholar ). These tumors may cause pain or mimic chronic pancreatitis, although many are detected incidentally on high-resolution abdominal imaging. IPMNs manifest with varying degrees of malignancy with either carcinoma in situ or invasive carcinoma seen in 62% of main-branch and 26% of side-branch IPMNs ( 2 Tanaka M. Fernández-del Castillo C. Adsay V. et al. International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas. Pancreatology. 2012; 12: 183-197 Abstract Full Text Full Text PDF PubMed Scopus (1694) Google Scholar ). Although certain imaging features, such as dilatation of the main pancreatic duct or mural nodularity, are concerning for malignancy, imaging alone cannot distinguish benign from malignant subtypes. International consensus guidelines recommend resection for all patients deemed fit for surgery with main-duct IPMNs, but the management of side-branch IPMNs is controversial ( 2 Tanaka M. Fernández-del Castillo C. Adsay V. et al. International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas. Pancreatology. 2012; 12: 183-197 Abstract Full Text Full Text PDF PubMed Scopus (1694) Google Scholar ). Furthermore, limited options are available for managing IPMNs in patients who are not ideal surgical candidates, warranting investigation into minimally invasive treatment options.

Purpose: to evaluate readmission rate and complications, in Patients Undergoing same-day discharge following percutaneons 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 1661174 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.