A Comparison of Yttrium-90 Microsphere Radioembolization to Hepatic Arterial Infusional Chemotherapy for Patients with Chemo-refractory Hepatic Colorectal Metastases.

OPINION STATEMENT: Patients with unresectable hepatic colorectal metastases who become chemo-refractory have limited treatment options. Systemic chemotherapies such as TAS102 and regorafenib have been used in the refractory setting, but with only modest improvement in overall survival compared to best supportive care. In patients with liver-only or liver-dominant disease, direct chemotherapy to the liver such as hepatic artery infusional (HAI) chemotherapy and radioembolization (yttrium-90 (Y90)) should be considered. Due to the difficulty of HAI therapy post Y90 for technical reasons, we recommend HAI therapy prior to Y90.

Pilot study of angiogenic response to yttrium-90 radioembolization with resin microspheres.

PURPOSE: To investigate the impact of radioembolization with yttrium-90 resin microspheres on the regulation of angiogenesis through observation of serial changes in a spectrum of angiogenic markers and other cytokines after therapy. MATERIALS AND METHODS: This prospective pilot study enrolled 22 patients with liver-dominant disease deriving from biopsy-proven hepatocellular carcinoma (HCC) (n = 7) or metastatic colorectal carcinoma (mCRC) (n = 15). Circulating angiogenic markers were measured from serum samples drawn at baseline and at time points after therapy ranging from 6 hours to 120 days. Using multiplex enzyme-linked immunosorbent assay, several classic angiogenesis factors (vascular endothelial growth factor [VEGF], angiopoietin-2 [Ang-2], basic fibroblast growth factor [bFGF], platelet-derived growth factor subunit BB [PDGF-BB], thrombospondin-1 [Tsp-1]) and nonclassic factors (follistatin, leptin, interleukin [IL]-8) were evaluated. RESULTS: Increases in cytokine levels ≥ 50% over baseline were observed in more than half of all patients studied for many cytokines, including classic angiogenic factors such as VEGF, Ang-2, and Tsp-1 as well as nonclassic factors IL-8 and follistatin (range, 36%-82% for all cytokines). Baseline cytokine levels in patients with overall survival (OS) < 6 months differed significantly from patients with longer survival for Ang-2 (P = .033) and IL-8 (P = .041). Patients with OS ≤ 6 months exhibited transient increases in VEGF and PDGF-BB after therapy compared with patients with OS > 6 months. CONCLUSIONS: Radioembolization is associated with early transient increases in many angiogenic cytokines. In this small sample size, some of these changes were associated with worse OS. This research has important implications for future studies of radioembolization with antiangiogenic therapy performed during and after the procedure.

Sequential Interventional Management of Osseous Neoplasms via Embolization, Cryoablation, and Osteoplasty.

The purpose of this study is to determine if sequential interventional therapy can become a mainstay option in providing palliation from fastidious osseous neoplasms in patients with pain refractory to oral analgesia and radiotherapy. This retrospective monocentric study was approved by our institutional review board. Between July 2012 and August 2014, we reviewed 15 patients (6 women, 9 men; age range of 36-81 years) who underwent embolization followed by cryoablation, with or without osteoplasty. Patient demographics and tumor characteristics, including primary histology and the location of metastasis, were included in our review. Pain intensity at baseline, after radiotherapy, and after sequential interventional therapy was reviewed using the hospital electronic medical record. The use of oral analgesia and procedural complications was also noted. Data was then assessed for normality and a two-tailed Student's t-test was performed on mean pain scores for difference phases of treatment. While radiotherapy offers pain relief with a mean pain score of 7.25 ±1.5 (p =<.0001), sequential interventional therapy results in better comfort as demonstrated by a mean pain score of 3.9 ± 2.6 (p=.0015). Moreover, all patients who reported oral analgesic use at presentation reported a decrease in their requirement after sequential interventional therapy. Embolization and cryoablation were performed in all patients, while osteoplasty was indicated in 6 cases. There was no difference in postprocedural pain intensity between patients who required osteoplasty and patients who did not (p = 0.7514). There were no complications observed during treatment. This retrospective study shows that sequential intervention with transarterial embolization, cryoablation, and osteoplasty is both safe and efficacious for bone pain refractory to the current standard of care. We demonstrated that this combination therapy has the potential to become an effective mainstay treatment paradigm in the palliative care of osseous neoplasm to improve quality of life.

Assessment of the Albumin-Bilirubin (ALBI) Grade as a Prognostic Indicator for Hepatocellular Carcinoma Patients Treated With Radioembolization.

OBJECTIVE: As the utility of Child-Pugh (C-P) class is limited by the subjectivity of ascites and encephalopathy, we evaluated a previously established objective method, the albumin-bilirubin (ALBI) grade, as a prognosticator for yttrium-90 radioembolization (RE) treatment for patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A total of 117 patients who received RE for HCC from 2 academic centers were reviewed and stratified by ALBI grade, C-P class, and Barcelona Clinic Liver Cancer stage. The overall survival (OS) according to these 3 criteria was evaluated by Kaplan-Meier survival analysis. The utilities of C-P class and ALBI grade as prognostic indicators were compared using the log-rank test. Multivariate Cox regression analysis was performed to identify additional predictive factors. RESULTS: Patients with ALBI grade 1 (n=49) had superior OS than those with ALBI grade 2 (n=65) (P=0.01). Meanwhile, no significant difference was observed in OS between C-P class A (n=100) and C-P class B (n=14) (P=0.11). For C-P class A patients, the ALBI grade (1 vs. 2) was able to stratify 2 clear and nonoverlapping subgroups with differing OS curves (P=0.03). Multivariate Cox regression test identified alanine transaminase, Barcelona Clinic Liver Cancer stage, and ALBI grade as the strongest prognostic factors for OS (P<0.10). CONCLUSIONS: ALBI grade as a prognosticator has demonstrated clear survival discrimination that is superior to C-P class among HCC patients treated with RE, particularly within the subgroup of C-P class A patients. ALBI grade is useful for clinicians to make decisions as to whether RE should be recommended to patients with HCC.

Endovascular treatment of pulmonary embolism: Selective review of available techniques.

Acute pulmonary embolism (PE) is the third most common cause of death in hospitalized patients. The development of sophisticated diagnostic and therapeutic modalities for PE, including endovascular therapy, affords a certain level of complexity to the treatment of patients with this important clinical entity. Furthermore, the lack of level I evidence for the safety and effectiveness of catheter directed therapy brings controversy to a promising treatment approach. In this review paper, we discuss the pathophysiology and clinical presentation of PE, review the medical and surgical treatment of the condition, and describe in detail the tools that are available for the endovascular therapy of PE, including mechanical thrombectomy, suction thrombectomy, and fibrinolytic therapy. We also review the literature available to date on these methods, and describe the function of the Pulmonary Embolism Response Team.

Ultrasound-guided thrombin injection for treatment of superficial traumatic pseudoaneurysms and associated expanding hematomas: experience in five patients.

BACKGROUND: Angiography allows for excellent characterization and treatment of traumatic pseudoaneurysms. However, ultrasound-guided thrombin injection for pseudoaneurysm thrombosis allows for radiation-free treatment of superficial pseudoaneurysms and superficial expanding hematomas. METHODS: A retrospective review of 5 patient cases treated under this paradigm was performed following institutional review board approval. Outcomes following intervention were recorded and compared amongst the patient cohort. RESULTS: Ultrasound-guided closure of traumatic pseudoaneurysms allowed for reduced procedural times and procedural invasiveness. CONCLUSIONS: As demonstrated by the following cases, ultrasound guided thrombin injection is a good method of primary treatment for superficial pseudoaneurysms, or as an alternative treatment in cases where transcatheter embolization fails.

On the conformation of the COOH-terminal domain of the large mechanosensitive channel MscL.

COOH-terminal (S3) domains are conserved within the MscL family of bacterial mechanosensitive channels, but their function remains unclear. The X-ray structure of MscL from Mycobacterium tuberculosis (TbMscL) revealed cytoplasmic domains forming a pentameric bundle (Chang, G., R.H. Spencer, A.T. Lee, M.T. Barclay, and D.C. Rees. 1998. SCIENCE: 282:2220-2226). The helices, however, have an unusual orientation in which hydrophobic sidechains face outside while charged residues face inside, possibly due to specific crystallization conditions. Based on the structure of pentameric cartilage protein, we modeled the COOH-terminal region of E. coli MscL to better satisfy the hydrophobicity criteria, with sidechains of conserved aliphatic residues all inside the bundle. Molecular dynamic simulations predicted higher stability for this conformation compared with one modeled after the crystal structure of TbMscL, and suggested distances for disulfide trapping experiments. The single cysteine mutants L121C and I125C formed dimers under ambient conditions and more so in the presence of an oxidant. The double-cysteine mutants, L121C/L122C and L128C/L129C, often cross-link into tetrameric and pentameric structures, consistent with the new model. Patch-clamp examination of these double mutants under moderately oxidizing or reducing conditions indicated that the bundle cross-linking neither prevents the channel from opening nor changes thermodynamic parameters of gating. Destabilization of the bundle by replacing conservative leucines with small polar residues, or complete removal of COOH-terminal domain (Delta110-136 mutation), increased the occupancy of subconducting states but did not change gating parameters substantially. The Delta110-136 truncation mutant was functional in in vivo osmotic shock assays; however, the amount of ATP released into the shock medium was considerably larger than in controls. The data strongly suggest that in contrast to previous gating models (Sukharev, S., M. Betanzos, C.S. Chiang, and H.R. Guy. 2001a. NATURE: 409:720-724.), S3 domains are stably associated in both closed and open conformations. The bundle-like assembly of cytoplasmic helices provides stability to the open conformation, and may function as a size-exclusion filter at the cytoplasmic entrance to the MscL pore, preventing loss of essential metabolites.

Non-operative therapies for colorectal liver metastases.

Locoregional therapies for colorectal liver metastases complement systemic therapy by providing an opportunity for local control of hepatic spread. The armamentarium for liver-directed therapy includes ablative therapies, embolization, and stereotactic body radiation therapy. At this time, prospective studies comparing these modalities are limited and decision-making relies on a multidisciplinary approach for optimal patient management. Herein, we describe multiple therapeutic non-surgical procedures and an overview of the results of these treatments.

Vascular anomalies: A pictorial review of nomenclature, diagnosis and treatment.

Vascular anomalies, including vascular malformations and tumors, are frequently straightforward to detect; however, accurate diagnosis and appropriate treatment are often challenging. Misdiagnosis of these lesions can lead clinicians in the wrong direction when treating these patients, which can have unfavorable results. This review presents an overview of the classification systems that have been developed for the diagnosis of vascular lesions with a focus on the imaging characteristics. Pictorial examples of each lesion on physical examination, as well as non-invasive and minimally invasive imaging are presented. An overview of the endovascular treatment of these lesions is also given. In some cases, vascular anomalies may be associated with an underlying syndrome and several of the most commonly encountered syndromes are discussed. Understanding of the classification systems, familiarity with the treatment options and knowledge of the associated syndromes are essential for all physicians working with this patient population. The approach to the described entities necessitates an organized multi-disciplinary team effort, with diagnostic imaging playing an increasingly important role in the proper diagnosis and a combined interventional radiologic and surgical treatment method showing promising results.

Repair of a post-hepatectomy posterior sectoral duct injury secondary to anomalous bile duct anatomy using a novel combined surgical-interventional radiologic approach.

A 64-year-old woman with a completely transected posterior sectoral duct following extended hepatectomy underwent a combined operative procedure with interventional radiology and surgery to restore biliary-enteric drainage. The anterior and posterior sectoral ducts were identified, and catheters were inserted into both systems. The posterior sectoral catheter was placed intraoperatively through a preoperatively placed sheath, and a new tunnel was created through the regenerated liver surface. Biliary-enteric anastomoses were created over the stents.

Evaluation of hepatic tumor response to yttrium-90 radioembolization therapy using texture signatures generated from contrast-enhanced CT images.

RATIONALE AND OBJECTIVES: The aim of this study was to explore the use of texture features generated from liver computed tomographic (CT) datasets as potential image-based indicators of patient response to radioembolization (RE) with yttrium-90 ((90)Y) resin microspheres, an emerging locoregional therapy for advanced-stage liver cancer. MATERIALS AND METHODS: Overall posttherapy survival and percent change in serologic tumor marker at 3 months posttherapy represent the primary clinical outcomes in this study. Thirty advanced-stage liver cancer cases (primary and metastatic) treated with RE over a 3-year period were included. Texture signatures for tumor regions, which were delineated to reveal boundaries with normal regions, were computed from pretreatment contrast-enhanced liver CT studies and evaluated for their ability to classify patient serologic response and survival. RESULTS: A series of systematic leave-one-out cross-validation studies using soft-margin support vector machine (SVM) classifiers showed hepatic tumor texton and local binary pattern (LBP) signatures both achieve high accuracy (96%) in discriminating subjects in terms of their serologic response. The image-based indicators were also accurate in classifying subjects by survival status (80% and 93% accuracy for texton and LBP signatures, respectively). CONCLUSIONS: Hepatic texture signatures generated from tumor regions on pretreatment triphasic CT studies were highly accurate in differentiating among subjects in terms of serologic response and survival. These image-based computational markers show promise as potential predictive tools in candidate evaluation for locoregional therapy such as RE.

Antegrade pampiniform plexus venography in recurrent varicocele: Case report and anatomy review.

Varicoceles are often treated with percutaneous embolization, using fibered coils and sclerosing agents, with the latter targeted at occlusion of pre-existing collateral veins. While various methods of surgical and embolization treatment are available, varicoceles may still recur from venous collateralization. We present a case, where following demonstration of complete occlusion of the right and left gonadal veins, direct puncture of the pampiniform venous plexus under ultrasound guidance revealed recurrent varicoceles supplied by anastomoses from the ipsilateral saphenous and femoral veins to the pampiniform plexus. In doing so, we describe a technique of percutaneous pampiniform venography in a case where the pertinent anatomy was not easily demonstrated by other methods.