The phosphatidylserine targeting antibody bavituximab plus pembrolizumab in unresectable hepatocellular carcinoma: a phase 2 trial.

Immune checkpoint inhibitors targeting PD-1/L1 have modest efficacy in hepatocellular carcinoma as single agents. Targeting membranous phosphatidylserine may induce pro-inflammatory and -immune stimulating effects that enhance immunotherapy activity. This hypothesis was tested in a single-arm phase 2 trial evaluating frontline bavituximab, a phosphatidylserine targeting antibody, plus pembrolizumab (anti-PD-1) in patients with unresectable hepatocellular carcinoma (NCT03519997). The primary endpoint was investigator-assessed objective response rate among evaluable patients, and secondary end points included progression-free survival, incidence of adverse events, overall survival, and duration of response. Among 28 evaluable patients, the confirmed response rate was 32.1%, which met the pre-specified endpoint, and the median progression-free survival was 6.3 months (95% CI, 1.3-11.3 months). Treatment related-adverse events of any grade occurred in 45.7% of patients, with grade 3 or greater adverse events in 14.3% of patients. Adverse events of any cause were observed in 33 patients (94.3%), with grade 3 or greater adverse events in 11 patients (31.4%). Prespecified exploratory analyses of baseline tumor specimens showed that a depletion of B cells, and the presence of fibrotic tissue and expression of immune checkpoints in stroma was associated with tumor response. These results suggest that targeting phosphatidylserine may lead to synergistic effects with PD-1 blockade without increasing toxicity rates, and future studies on this therapeutic strategy may be guided by biomarkers characterizing the pre-treatment tumor microenvironment.

Diagnostic performance of the adrenal vein to inferior vena cava aldosterone ratio in classifying the subtype of primary aldosteronism.

Adrenal vein sampling (AVS) is the standard procedure for distinguishing unilateral primary aldosteronism (PA) from bilateral PA. In cases where only one adrenal vein is successfully cannulated, it has been suggested that subtype classification can be determined based on the ratio of the concentration of aldosterone between the adrenal vein and the inferior vena cava (AV/IVC index). However, diagnostic performance of the ipsilateral versus contralateral AV/IVC index in predicting lateralization has not been directly compared. In a retrospective cohort of 133 patients with confirmed PA who underwent successful AVS, the performance of the AV/IVC index to predict laterality was evaluated and the area under the receiver operating characteristic (AUROC) curves was calculated. In detecting left unilateral PA (n = 47), the AUROC of the right AV/IVC index (RAV/IVC) was significantly higher than the AUROC of the left AV/IVC (LAV/IVC) index (0.967 vs. 0.871, p = 0.008). In detecting right unilateral PA (n = 30), the AUROC of the LAV/IVC index tended to be higher than that of the RAV/IVC index, but the difference did not reach statistical significance (0.966 vs. 0.906, p = 0.08). In detecting left unilateral PA, the sensitivities of the RAV/IVC and LAV/IVC indices were 83% and 46%, respectively, while the specificities of both were above 90%. In detecting right unilateral PA, the sensitivities of the LAV/IVC and RAV/IVC indices were 80% and 43%, respectively, while the specificities of both were above 90%. The AV/IVC index has superior diagnostic performance in detecting contralateral unilateral PA compared to ipsilateral unilateral PA.

ACR Appropriateness Criteria® Imaging of Deep Inferior Epigastric Arteries for Surgical Planning (Breast Reconstruction Surgery): 2022 Update.

Breast cancer is the most common malignancy in women in the United States, with surgical options including lumpectomy and mastectomy followed by breast reconstruction. Deep inferior epigastric perforator (DIEP) flap is a muscle-sparing perforator free flap breast reconstruction technique, which uses the deep inferior epigastric artery (DIEA) perforators to create a vascular pedicle. Multiple perforators are identified by preoperative imaging, which are typically ranked based on size, location, and intramuscular course. The goal of preoperative imaging is to aid the surgical team in preoperative planning given the variability of the DIEA perforator branches anatomy between patients. The objective of this document is to review the imaging modalities that can be used preoperatively to identify the optimal perforator and thereby reduce intraoperative complications, reduce postoperative complications, and improve clinical outcomes. The ACR 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 in which peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

ACR Appropriateness Criteria® Lower Extremity Arterial Claudication-Imaging Assessment for Revascularization: 2022 Update.

Arterial claudication is a common manifestation of peripheral artery disease. This document focuses on necessary imaging before revascularization for claudication. Appropriate use of ultrasound, invasive arteriography, MR angiography, and CT angiography are discussed. The ACR 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.

Postmortem study of organ-specific toxicity in glioblastoma patients treated with a combination of temozolomide, irinotecan and bevacizumab.

PURPOSE: Systemic chemotherapy including monotherapy with temozolomide (TMZ) or bevacizumab (BEV); two-drug combinations, such as irinotecan (IRI) and BEV, TMZ and BEV and a three-drug combination with TMZ, IRI and BEV (TIB) have been used in treating patients with progressive high-grade gliomas including glioblastoma (GBM). Most patients tolerated these regimens well with known side effects of hypertension, proteinuria, and reversible clinical myelosuppression (CM). However, organ- or system- specific toxicities from chemotherapy agents have never been examined by postmortem study. This is the largest cohort used to address this issue in glioma patients. METHODS: Postmortem tissues (from all major systems and organs) were prospectively collected and examined by standard institution autopsy and neuropathological procedures from 76 subjects, including gliomas (N = 68, 44/M, and 24/F) and brain metastases (N = 8, 5/M, and 3/F) between 2009 and 2019. Standard hematoxylin and eosin (H&E) were performed on all major organs including brain specimens. Electronic microscopic (EM) study was carried out on 14 selected subject's kidney samples per standard EM protocol. Medical records were reviewed with adverse events (AEs) analyzed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. A swimmer plot was utilized to visualize the timelines of patient history by treatment group. The binary logistic regression models were performed to explore any associations between treatment strategies and incident myelosuppression. RESULTS: Twenty-four glioma subjects were treated with TIB [median: 5.5 (range: 1-25) cycles] at tumor recurrence. Exposure to IRI significantly increased the frequency of CM (p = 0.05). No unexpected adverse events clinically, or permanent end-organ damage during postmortem examination was identified in glioma subjects who had received standard or prolonged duration of BEV, TMZ or TIB regimen-based chemotherapies except rare events of bone marrow suppression. The most common causes of death (COD) were tumor progression (63.2%, N = 43) followed by aspiration pneumonia (48.5%, N = 33) in glioma subjects. No COD was attributed to acute toxicity from TIB. The study also demonstrated that postmortem kidney specimen is unsuitable for studying renal ultrastructural pathological changes due to autolysis. CONCLUSION: There is no organ or system toxicity by postmortem examinations among glioma subjects who received BEV, TMZ or TIB regimen-based chemotherapies regardless of durations except for occasional bone marrow suppression and reversible myelosuppression clinically. IRI, but not the extended use of TMZ, significantly increased CM in recurrent glioma patients. COD most commonly resulted from glioma tumor progression with infiltration to brain stem and aspiration pneumonia.

PSMA-Targeting Imaging and Theranostic Agents-Current Status and Future Perspective.

In the past two decades, extensive efforts have been made to develop agents targeting prostate-specific membrane antigen (PSMA) for prostate cancer imaging and therapy. To date, represented by two recent approvals of [68Ga]Ga-PSMA-11 and [18F]F-DCFPyL by the United States Food and Drug Administration (US-FDA) for positron emission tomography (PET) imaging to identify suspected metastases or recurrence in patients with prostate cancer, PSMA-targeting imaging and theranostic agents derived from small molecule PSMA inhibitors have advanced to clinical practice and trials of prostate cancer. The focus of current development of new PSMA-targeting agents has thus shifted to the improvement of in vivo pharmacokinetics and higher specific binding affinity with the aims to further increase the detection sensitivity and specificity and minimize the toxicity to non-target tissues, particularly the kidneys. The main strategies involve systematic chemical modifications of the linkage between the targeting moiety and imaging/therapy payloads. In addition to a summary of the development history of PSMA-targeting agents, this review provides an overview of current advances and future promise of PSMA-targeted imaging and theranostics with focuses on the structural determinants of the chemical modification towards the next generation of PSMA-targeting agents.

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.

Venous thoracic outlet syndrome.

Venous thoracic outlet syndrome (vTOS) is a spectrum of disease caused by external compression of the subclavian vein as it passes through the costoclavicular space. Paget-Schroetter's Syndrome (PSS) or effort thrombosis is a subtype of vTOS where compression and microtrauma to subclavian vein from repetitive arm movements results in venous thrombosis. PSS or effort thrombosis mostly affects young otherwise healthy active individuals, and this further highlights the importance of this condition. Early diagnosis and aggressive early intervention aimed at complete resolution of acute symptoms and minimizing the risk of recurrence is ultimately important and increases the likelihood of the full restoration of limb function. Several noninvasive imaging techniques are currently available to confirm the initial diagnosis including Doppler ultrasound, contrast-enhanced computed tomography, and magnetic resonance imaging. Following diagnosis, multiple algorithms exist for the management of PSS and almost all require a multidisciplinary approach. Like any other condition involving the thrombosis of deep venous system, initial step in the management is anticoagulation. Catheter-directed therapies (CDT) have also a pivotal role as the initial treatment to resolve the acute thrombosis and establish venous patency. CDT combined with medical anticoagulation and surgical decompression are the components of most treatment algorithms for the management of patients suffering from PSS.

Popliteal artery entrapment syndrome.

Popliteal artery entrapment syndrome (PAES) is an uncommon cause of lower extremity exertional claudication due to external compression of vascular structures in the popliteal fossa. A developmental anomaly due to an aberrant relationship of the artery with the surrounding myofascial structures contributes to the vascular compromise. PAES presents in younger, athletic patients without atherosclerotic risk factors. Typical presentation of unilateral or bilateral, intermittent claudication in the feet and calves specifically after exercise and relieved by rest in a young person should prompt further evaluation. Early diagnosis and intervention is essential for preventing thromboembolic complication and in worst cases limb loss. Initial tests with Ankle Brachial indices or Doppler ultrasound with provocative maneuvers will prompt more definitive cross sectional imaging studies. CTA or MRA also with provocative maneuvers has a high sensitivity and specificity and will clinch the diagnosis. There are six subtypes based on the relationship of the vascular structure with surround myofascial structures. CTA and MRA can characterize the subtypes and guide surgical planning. Catheter directed thrombolysis may be attempted adjunctively to reduce surgical thrombectomy or resolve distal emboli; however, myotendinous decompression with or without vascular repair is the definitive treatment. Long term surgical outcomes are satisfactory when the distal circulation is preserved.

Selection and Characterization of Vimentin-Binding Aptamer Motifs for Ovarian Cancer.

The application of aptamers in biomedicine is emerging as an essential technology in the field of cancer research. As small single-stranded DNA or RNA ligands with high specificity and low immunogenicity for their targets, aptamers provide many advantages in cancer therapeutics over protein-based molecules, such as antibodies. Vimentin is an intermediate filament protein that is overexpressed in endothelial cells of cancerous tissue. High expression levels of vimentin have been associated with increased capacity for migration and invasion of the tumor cells. We have selected and identified thioated aptamers with high specificity for vimentin using human ovarian cancer tissues. Tentative binding motifs were chosen for two vimentin aptamers based on predicted secondary structures. Each of these shorter, tentative binding motifs was synthesized, purified, and characterized via cell binding assays. Two vimentin binding motifs with high fidelity binding were selected and further characterized via cell and tissue binding assays, as well as flow cytometric analysis. The equilibrium binding constants of these small thioated aptamer constructs were also determined. Future applications for the vimentin binding aptamer motifs include conjugation of the aptamers to synthetic dyes for use in targeted imaging and therapy, and ultimately more detailed and precise monitoring of treatment response and tumor progression in ovarian pathology.

Hepatic Trauma Interventions.

The liver is the second most commonly involved solid organ (after spleen) to be injured in blunt abdominal trauma, but liver injury is the most common cause of death in such trauma. In patients with significant blunt abdominal injury, the liver is involved approximately 35 to 45% of the time. Its large size also makes it a vulnerable organ, commonly injured in penetrating trauma. Other than its position and size, the liver is surrounded by fragile parenchyma and its location under the diaphragm makes it vulnerable to shear forces during deceleration injuries. The liver is also a vascular organ made of large, thin-walled vessels with high blood flow. In severe hepatic trauma, hemorrhage is a common complication and uncontrolled bleeding is usually fatal. In fact, in patients with severe abdominal trauma, liver injury is the primary cause of death. This article reviews the clinical presentation of patients with liver injury, the grading system for such injuries that is most frequently used, and management of the patient with liver trauma.

Retrospective CT/MRI Texture Analysis of Rapidly Progressive Hepatocellular Carcinoma.

Rapidly progressive hepatocellular carcinoma (RPHCC) is a subset of hepatocellular carcinoma that demonstrates accelerated growth, and the radiographic features of RPHCC versus non-RPHCC have not been determined. The purpose of this retrospective study was to use baseline radiologic features and texture analysis for the accurate detection of RPHCC and subsequent improvement of clinical outcomes. We conducted a qualitative visual analysis and texture analysis, which selectively extracted and enhanced imaging features of different sizes and intensity variation including mean gray-level intensity (mean), standard deviation (SD), entropy, mean of the positive pixels (MPP), skewness, and kurtosis at each spatial scaling factor (SSF) value of RPHCC and non-RPHCC tumors in a computed tomography (CT) cohort of n = 11 RPHCC and n = 11 non-RPHCC and a magnetic resonance imaging (MRI) cohort of n = 13 RPHCC and n = 10 non-RPHCC. There was a statistically significant difference across visual CT irregular margins p = 0.030 and CT texture features in SSF between RPHCC and non-RPHCC for SSF-6, coarse-texture scale, mean p = 0.023, SD p = 0.053, MPP p = 0.023. A composite score of mean SSF-6 binarized + SD SSF-6 binarized + MPP SSF-6 binarized + irregular margins was significantly different between RPHCC and non-RPHCC (p = 0.001). A composite score ≥3 identified RPHCC with a sensitivity of 81.8% and specificity of 81.8% (AUC = 0.884, p = 0.002). CT coarse-texture-scale features in combination with visually detected irregular margins were able to statistically differentiate between RPHCC and non-RPHCC. By developing an image-based, non-invasive diagnostic criterion, we created a composite score that can identify RPHCC patients at their early stages when they are still eligible for transplantation, improving the clinical course of patient care.

Percutaneous Venous Interventions in The Pulmonary Vascular, Central and Peripheral Venous Systems: How to Recognize, Avoid and Treat Complications.

Endovascular treatment of venous disease encompasses a broad range of interventions. Both central and peripheral venous interventions can range from the simple to the complex which increases the need for proper patient selection, procedural planning and technical proficiency. The following article will discuss the importance of avoiding, recognizing and addressing complications associated with venous interventions. Our goal is to raise awareness and educate to help the reader improve performance.

Image-Guided Biliary Interventions: How to Recognize, Avoid, or Get Out of Trouble.

Percutaneous biliary interventions have a well-established role in the management of hepatobiliary diseases. Good outcomes include recognizing and avoiding complications. This section will cover the "standard" technique of percutaneous biliary drainage, pearls to decrease the risk of problems, and approaches to treat those complications in patients undergoing percutaneous transhepatic cholangiography and percutaneous transhepatic biliary drainage.

Percutaneous Gastrostomy: How to Recognize, Avoid, or Get Out of Trouble.

Placement of gastrostomy tubes can be done with different techniques. The radiologic-guided tube placement relies on image guidance for safe placement of the tube. A thorough knowledge of the immediate and delayed hazards is essential. This article outlines the potential complications and how to recognize, avoid, and treat them. Several clinical examples are included. Key Words: gastrostomy, complication, feeding tubes, image guidance.

Image-Guided Nephrostomy Interventions: How to Recognize, Avoid, or Get Out of Trouble.

Image-guided percutaneous nephrostomy is a relatively safe and successful procedure for access to the renal collecting system for multiple purposes including relief of urinary obstruction, urinary diversion, access for endourologic procedures, and diagnostic testing. Although placing a percutaneous nephrostomy catheter is most times straightforward, providing immediate benefit for the patient and satisfaction for the practitioner, there can be situations that make the procedure more difficult or risky. A thorough review of the patient's imaging and medical record will help to set a path for success. However, there may be innuendos and unforeseen circumstances that occur. Having knowledge of most of these "stumbling blocks" and how to deal with them will keep you on the path. This paper serves to fill some of that mental file with the aim to increase clinical success.

Portal Venous Interventions: How to Recognize, Avoid, or Get Out of Trouble in Transjugular Intrahepatic Portosystemic Shunt (TIPS), Balloon Occlusion Sclerosis (ie, BRTO), and Portal Vein Embolization (PVE).

Portal venous interventions comprise a large portion of many Interventional Radiology practices today, and remain some of the more technically challenging cases in one's repertoire of procedures. The patients upon whom these procedures are performed are often critically ill, have decompensated disease, or are burdened with comorbid conditions such that they are poor surgical candidates. This leaves them with few options outside the care of Interventional Radiology. Some portal venous interventions, such as transjugular intrahepatic portosystemic shunt, have an established history of excellent clinical success with numerous technical advancements over the years helping to improve outcomes. Others, like balloon occlusion sclerotherapy or portal venous recanalization, are less well established but are nonetheless invaluable in the treatment of portal venous diseases. The goal of this article is to help dispel some of the anxiety experienced by individuals performing the three main procedures of the portal venous system, namely transjugular intrahepatic portosystemic shunt, balloon-occlusion retrograde transvenous obliteration, and portal vein embolization.