A Pilot Study of Pembrolizumab in Combination With Y90 Radioembolization in Subjects With Poor Prognosis Hepatocellular Carcinoma.

BACKGROUND: Combination checkpoint inhibition therapy with yttrium-90 (Y90) radioembolization represents an emerging area of interest in the treatment of advanced hepatocellular carcinoma (HCC). HCRN GI15-225 is an open-label, single-arm multicenter, pilot study (NCT03099564). METHODS: Eligible patients had poor prognosis, localized HCC defined as having portal vein thrombus, multifocal disease, and/or diffuse disease that were not eligible for liver transplant or surgical resection. Patients received pembrolizumab 200 mg intravenously every 3 weeks in conjunction with glass yttrium-90 (Y90) radioembolization TheraSphere. Primary endpoint was 6-month progression-free survival (PFS6) per RECIST 1.1. Secondary endpoints included time to progression (TTP), objective response rate (ORR), overall survival (OS), and safety/tolerability. RESULTS: Between October 23, 2017 and November 24, 2020, 29 patients were enrolled: 2 were excluded per protocol. Fifteen of the remaining 27 patients were free of progression at 6 months (55.6%; 95% CI, 35.3-74.5) with median PFS 9.95 months (95% CI, 4.14-15.24) and OS 27.30 months (95% CI, 10.15-39.52). One patient was not evaluable for response due to death; among the remaining 26 patients, ORR was 30.8% (95% CI, 14.3-51.8) and DCR was 84.6% (95% CI, 65.1-95.6). CONCLUSION: In patients with localized, poor prognosis HCC, pembrolizumab in addition to glass Y90 radioembolization demonstrated promising efficacy and safety consistent with prior observations (ClinicalTrials.gov Identifier: NCT03099564; IRB Approved: 16-3255 approved July 12, 2016).

ACR Appropriateness Criteria® Dialysis Fistula Malfunction.

The creation and maintenance of a dialysis access is vital for the reduction of morbidity, mortality, and cost of treatment for end stage renal disease patients. One's longevity on dialysis is directly dependent upon the quality of dialysis. This quality hinges on the integrity and reliability of the access to the patient's vascular system. All methods of dialysis access will eventually result in dialysis dysfunction and failure. Arteriovenous access dysfunction includes 3 distinct classes of events, namely thrombotic flow-related complications or dysfunction, nonthrombotic flow-related complications or dysfunction, and infectious complications. The restoration of any form of arteriovenous access dysfunction may be supported by diagnostic imaging, clinical consultation, percutaneous interventional procedures, surgical management, or a combination of these methods. This document provides a rigorous evaluation of how variants of each form of dysfunction may be appraised and approached systematically. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Patient-reported symptoms and interest in symptom monitoring in HCC treated with locoregional therapies: A qualitative study.

BACKGROUND: Patient-reported outcomes (PRO) measures relevant to domains most important to patients with HCC who received locoregional therapies are needed to advance patient-centered research. Furthermore, electronic PRO monitoring in clinical care has been shown to reduce hospitalizations and deaths in patients with other cancers. We conducted a qualitative study among patients with HCC who recently received locoregional therapies to (1) identify common and distressing posttreatment symptoms to prioritize PRO domain selection and (2) gauge interest in an electronic PRO symptom monitoring system. METHODS: We performed semi-structured telephone interviews among adult patients who received locoregional therapies (median of 26 days after treatment) for treatment-naïve HCC at a single tertiary care center. Interviews were conducted until thematic saturation was reached. Qualitative content analysis was conducted to identify emerging themes and sub-themes. RESULTS: Ten of 26 patients (38%) reported at least 1 symptom before treatment. In contrast, all participants (n = 26) with recently treated HCC reported at least 1 posttreatment physical symptom, with the most common being appetite loss (73%), fatigue (58%), abdominal pain (46%), and nausea (35%). Most participants (77%) stated they saw potential benefits in posttreatment ePRO symptom monitoring. CONCLUSIONS: Posttreatment symptoms after HCC locoregional therapies are common and often severe. These data can inform and prioritize PRO domain selection. Patients are interested in ePRO monitoring to monitor and proactively address posttreatment symptoms. Given the clinical benefits in patients with metastatic cancers, ePRO monitoring warrants investigation in patients with HCC.

Thermal ablation compared to stereotactic body radiation therapy for hepatocellular carcinoma: A multicenter retrospective comparative study.

BACKGROUND AIMS: Early-stage HCC can be treated with thermal ablation or stereotactic body radiation therapy (SBRT). We retrospectively compared local progression, mortality, and toxicity among patients with HCC treated with ablation or SBRT in a multicenter, US cohort. APPROACH RESULTS: We included adult patients with treatment-naïve HCC lesions without vascular invasion treated with thermal ablation or SBRT per individual physician or institutional preference from January 2012 to December 2018. Outcomes included local progression after a 3-month landmark period assessed at the lesion level and overall survival at the patient level. Inverse probability of treatment weighting was used to account for imbalances in treatment groups. The Cox proportional hazard modeling was used to compare progression and overall survival, and logistic regression was used for toxicity. There were 642 patients with 786 lesions (median size: 2.1 cm) treated with ablation or SBRT. In adjusted analyses, SBRT was associated with a reduced risk of local progression compared to ablation (aHR 0.30, 95% CI: 0.15-0.60). However, SBRT-treated patients had an increased risk of liver dysfunction at 3 months (absolute difference 5.5%, aOR 2.31, 95% CI: 1.13-4.73) and death (aHR 2.04, 95% CI: 1.44-2.88, p < 0.0001). CONCLUSIONS: In this multicenter study of patients with HCC, SBRT was associated with a lower risk of local progression compared to thermal ablation but higher all-cause mortality. Survival differences may be attributable to residual confounding, patient selection, or downstream treatments. These retrospective real-world data help guide treatment decisions while demonstrating the need for a prospective clinical trial.

ACR Appropriateness Criteria® Noncerebral Vasculitis.

Noncerebral vasculitis is a wide-range noninfectious inflammatory disorder affecting the vessels. Vasculitides have been categorized based on the vessel size, such as large-vessel vasculitis, medium-vessel vasculitis, and small-vessel vasculitis. In this document, we cover large-vessel vasculitis and medium-vessel vasculitis. Due to the challenges of vessel biopsy, imaging plays a crucial role in diagnosing this entity. While CTA and MRA can both provide anatomical details of the vessel wall, including wall thickness and enhancement in large-vessel vasculitis, FDG-PET/CT can show functional assessment based on the glycolytic activity of inflammatory cells in the inflamed vessels. Given the size of the vessel in medium-vessel vasculitis, invasive arteriography is still a choice for imaging. However, high-resolution CTA images can depict small-caliber aneurysms, and thus can be utilized in the diagnosis of medium-vessel vasculitis. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR Appropriateness Criteria® Suspected Retroperitoneal Bleed.

The initial diagnosis of retroperitoneal bleeding can be challenging by physical examination and clinical presentation. Prompt imaging can make the diagnosis and be lifesaving. When selecting appropriate imaging for these patient's, consideration must be made for sensitivity and ability to image the retroperitoneum, as well as speed of imaging.The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Current Approach to Planning Angiography and MAA Administration.

Transarterial radioembolization of primary and secondary hepatic malignancies utilizing yttrium-90 microspheres is a commonly performed treatment by interventional radiologists. Traditionally performed as a two-part procedure, a diagnostic angiography is performed 1 to 3 weeks prior to treatment with the injection of technetium-99m-macroaggregated albumin followed by planar scintigraphy in the nuclear medicine department. Careful attention must be paid to the details during the diagnostic angiography to ensure the delivery of a safe and optimal dose to the diseased liver and to minimize radiation-induced damage to both unaffected liver and adjacent structures. In this article, we will review the steps and considerations that must be made during the angiography planning and discuss current and future areas of research.

Creating an Open-Access Educational Radiology Website for Medical Students: A Guide for Radiology Educators.

RATIONALE AND OBJECTIVES: Studies of medical school clerkship websites have reported efficient time management, resource utilization, and hands-on activities. We built a website devoted to medical student education in radiology to address student, educator, and school curricular needs and surveyed students to assess their satisfaction with the site. MATERIALS AND METHODS: The website was created using an easily-recalled name, no-cost institutional software, and no-cost enterprise-level university hardware. The main menu links to the student formal didactic lecture calendar, custom-built health sciences library e-resources in radiology, American College of Radiology Appropriateness Criteria, each radiology course page, and teaching files. Each course tab includes faculty-curated content from course lectures, supplemental articles and educational modules. At 6, 12, and 24 months, website analytics were assessed. At 12 and 24 months postimplementation, data were evaluated to include student assessment and satisfaction surveys and student course comments. This project was IRB-exempted. RESULTS: At 6 months, the website had received 5792 views, at 12 months 10,022 views and at 24 months 19,478 views. The website homepage with the formal didactic lecture calendar received 7156 views, the general clerkship page 4233 views, the teaching file page 3884, and thereafter subspecialty pages as follows: breast 1478, body 633, pediatrics 361, neuro 346, cardiothoracic 291, musculoskeletal 249, vascular interventional 178. One hundred fifty-two of 240 (63.3%) of students surveyed replied. Of students who utilized the website on the satisfaction survey, 80 of 97 (82.5%) indicated ratings of "extremely informative" and "very informative" to the question "How would you rate the website?." Students indicated convenience and structure as website strengths in their postcourse evaluations. CONCLUSION: The radiology medical student website incorporates demands and needs of today's students, faculty, and our medical school. A radiology clerkship website for medical students centralizes access to course resources and promotes an active learning experience with high satisfaction. Instructions on setting up a website are offered to today's radiology educators, including pearls and pitfalls.

ACR Appropriateness Criteria® Suspected Upper Extremity Deep Vein Thrombosis.

This publication includes the appropriate imaging modalities to assess suspected deep vein thrombosis in the upper extremities. Ultrasound duplex Doppler is the most appropriate imaging modality to assess upper-extremity deep vein thrombosis. It is a noninvasive test, which can be performed at the bedside and used for serial evaluations. Ultrasound can also directly identify thrombus by visualizing echogenic material in the vein and by lack of compression of the vein walls from manual external pressure. It can indirectly identify thrombus from altered blood-flow patterns. It is most appropriate in the evaluation of veins peripheral to the brachiocephalic vein. CT venography and MR venography are not first-line imaging tests, but are appropriate to assess the central venous structures, or to assess the full range of venous structures from the hand to the right atrium. Catheter venography is appropriate if therapy is required. Radionuclide venography and chest radiography are usually not appropriate to assess upper-extremity deep vein thrombosis. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR Appropriateness Criteria® Suspected Lower Extremity Deep Vein Thrombosis.

Suspected lower extremity deep venous thrombosis is a common clinical scenario which providers seek a reliable test to guide management. The importance of confidently making this diagnosis lies in the 50% to 60% risk of pulmonary embolism with untreated deep vein thrombosis and subsequent mortality of 25% to 30%, balanced with the risks of anticoagulation. The ACR Appropriateness Criteria Expert Panel on Vascular Imaging reviews the current literature regarding lower extremity deep venous thrombosis and compared various imaging modalities including ultrasound, MR venography, CT venography, and catheter venography. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Development of bilateral coronary artery aneurysms in a child with Noonan syndrome.

Noonan syndrome is a constellation of congenital malformations including heart defects, facial anomalies and short stature. The cardiovascular defects are variable and extensive, with the most common being pulmonary stenosis and hypertrophic cardiomyopathy. Coronary artery anomalies have only been reported in a few cases. We report a child with Noonan syndrome status post pulmonary stenosis and atrial septal defect repair, who developed bilateral coronary artery aneurysms. The aneurysms were diagnosed with both cardiac magnetic resonance imaging and coronary computed tomography angiography. There had been no evidence of them on a cardiac MR exam 5 years previously.

Delayed endoluminal vacuum therapy for rectal anastomotic leaks after rectal resection in a swine model: a new treatment option.

Anastomotic leaks are a dreaded surgical complication following colorectal operations. Creation of a temporary proximal diverting ileostomy is used in high-risk anastomoses, however, additional surgical risk is accumulated with its creation and reversal. Endoluminal vacuum therapy has been shown to seal anastomotic defects in the prophylactic setting in a pig model and we hypothesized it could be utilized in a delayed fashion to rescue subjects with an active anastomotic leak. Yorkshire pigs underwent rectal resection, intentional leak confirmed by fluoroscopy, and endoluminal vacuum therapy device placement to low continuous suction. Following treatment, a contrast enema and necropsy was performed for gross and histopathology. Pigs underwent 2 (or 5) days of free intraperitoneal leak prior to device placement and 5 (or 7) subsequent days of endoluminal vacuum therapy. Six of seven early-treated pigs sealed their anastomotic defect, while two of the four treated pigs in this extended group sealed the defect. Endoluminal vacuum therapy is feasible and well tolerated in a pig model, and it has been shown to seal a significant number of freely leaking anastomoses in the early period (86%). This technology warrants further study as it may provide a noninvasive means to treatment of anastomotic leaks.

Subsurface ecosystem resilience: long-term attenuation of subsurface contaminants supports a dynamic microbial community.

The propensity for groundwater ecosystems to recover from contamination by organic chemicals (in this case, coal-tar waste) is of vital concern for scientists and engineers who manage polluted sites. The microbially mediated cleanup processes are also of interest to ecologists because they are an important mechanism for the resilience of ecosystems. In this study we establish the long-term dynamic nature of a coal-tar waste-contaminated site and its microbial community. We present 16 years of chemical monitoring data, tracking responses of a groundwater ecosystem to organic contamination (naphthalene, xylenes, toluene, 2-methyl naphthalene and acenaphthylene) associated with coal-tar waste. In addition, we analyzed small-subunit (SSU) ribosomal RNA (rRNA) genes from two contaminated wells at multiple time points over a 2-year period. Principle component analysis of community rRNA fingerprints (terminal-restriction fragment length polymorphism (T-RFLP)) showed that the composition of native microbial communities varied temporally, yet remained distinctive from well to well. After screening and analysis of 1178 cloned SSU rRNA genes from Bacteria, Archaea and Eukarya, we discovered that the site supports a robust variety of eukaryotes (for example, alveolates (especially anaerobic and predatory ciliates), stramenopiles, fungi, even the small metazoan flatworm, Suomina) that are absent from an uncontaminated control well. This study links the dynamic microbial composition of a contaminated site with the long-term attenuation of its subsurface contaminants.