From the SIR Residents and Fellows Sections (SIRRFS)

Teaching Topic: CT–Guided Bone Biopsies in Metastatic Castration-Resistant Prostate Cancer: Factors Predictive of Maximum Tumor Yield.

Holmes MG, Foss E, Joseph G, Foye A, et al. CT–Guided Bone Biopsies in Metastatic Castration-Resistant Prostate Cancer: Factors Predictive of Maximum Tumor Yield. J Vasc Interv Radiol. 2017. 28:1073-1081.

Click here for abstract

Patients with metastatic prostate cancer undergo biopsy for histological as well as molecular analysis after treatment failure. Prior studies have not addressed the factors that determine adequacy of biopsy samples especially as they relate to molecular analysis. This study was done as part of a larger multi-center study to evaluate mechanisms of resistance in metastatic castrate-resistant prostate cancer (mCRPC). The main purpose was to assess the overall success rates for histological and molecular analysis of CT guided bone biopsies performed for mCRPC. The secondary purpose was to evaluate the clinical, imaging, and technical factors that improved diagnostic yields in this cohort.

72 patients who underwent 80 CT-guided biopsies were analyzed as part of this study. Patients included in this study had histologically confirmed prostate cancer, metastatic disease amenable to image guided biopsy, and disease progression in light of biochemical castration. Successful biopsy was defined as ≥ 5% tumor on histological evaluation (80 biopsy samples) and adequate sample for next-generation sequencing (55 biopsy samples). All procedures were performed with CT guidance by four MSK trained radiologists. Biopsy sites were chosen by the operator; all sites of prior external beam radiation therapy were excluded. Clinical factors evaluated as part of the study included hemoglobin levels, PSA, lactate dehydrogenase, and alkaline phosphatase one month around the time of biopsy. Additionally, the authors also evaluated use of bone-modifying agents and length of therapy, second line therapy (immunotherapy & chemotherapy), androgen deprivation therapy, and external beam radiation. Imaging factors in the study included anatomic location of the biopsy specimen (ilium, pelvis, extrapelvis), size of lesion in cm (<2, 2-4 , >4), qualitative analysis of the lesion (dense sclerosis, subtle sclerosis, mix of dense and subtle sclerosis, or radiolucent lesions), lesion margins (ill-defined, well-circumscribed), and interval growth (>25% over past two years). Technical factors included location of the sample (central versus peripheral), quantitative attenuation at biopsy site, type of biopsy needle, distance of biopsy sample from cortex to lesion edge, and number of core samples (≤2, 3, 4, ≥ 5).

The overall success rate was 69% for histological evaluation and 64% for molecular evaluation. The only clinical variable associated with success for biopsy was alkaline phosphatase > 110 U/L (83% compared to 50% for <110 U/L). Imaging features associated with increased yield included lesions with mixed density and lucent lesions, lesions with mean attenuation ≤ 475 at biopsy site, lesions with ill-defined margins, and lesions with >25% growth in the last two years. There were no technical parameters that reached statistical significance for biopsy success. However, a distance of 1.6 cm of the lesion from cortex and peripheral location of the sample resulted in statistical trend towards significance. The location of the lesion, the specific biopsy system or the number of core samples did not meet statistical significance. There was a 20% difference in the biopsy success rate between ≤2 core and three core samples (56% to 76%) but this did not reach statistical significance.

Clinical Pearls

• According to the study what imaging findings, aside from safety, are important when selecting a target lesion for patients with mCRPC undergoing molecular testing?

• The imaging characteristics which lead to statistically improved yields included lesions that are less densely sclerotic, areas in the lesion with HU < 475, lesions with ill-defined margins, and lesions that have demonstrated at least 25% growth over the prior two years if imaging is available. Study by Sprtizer et al. had similar findings in regards to imaging findings that resulted in increased yield for biopsy sample. Some of the proposed reasons for decreased diagnostic yield in more sclerotic areas potentially stem from crushed bones damaging viable tumor and difficulty in processing the more densely sclerotic samples for hematoxylin-eosin staining.

• At the genitourinary tumor board a patient with castration resistant metastatic prostate cancer is presented and the team wants to pursue targeted therapy. The team asks you as the interventional radiologist what is the likelihood of successful biopsy for next generation sequencing?

• Adequate sample for molecular analysis depends on multiple factors including clinical findings, lesion characteristics, and technical parameters (including the experience of the interventional radiologist). In the current literature the likelihood of gaining adequate sample for molecular analysis is between 40% to 64% according to Spritzer et al. and the current study.

Questions to Consider

What impact does size of the lesion have on biopsy success rates?

Even though the biopsy success rates were not statistically different based on size of the lesion (<2, 2-4 , >4), there was a step-wise increase in biopsy success rates with increase in lesion size. From a practical perspective holding all other parameters the same, a large lesion is generally easier to target. Failure to reach statistical significance may be related to smaller cohorts.

What is the role of non-image guided biopsies in patients with metastatic prostate cancer?

Approximately 90% of patients with advanced prostate cancer will have boney metastatic disease. There are some centers/clinicians who perform non-image guided biopsies, of the iliac crest in patients with metastatic disease with reported success rates between 25% to 47%. However, the success rates for these biopsies is defined by histologic evaluation and not based on isolation of molecular tissues. With improvement in imaging, especially with prostate-specific membrane antigen PET/CTs , the clinically significant question is not whether these patients have metastatic disease but what is the next step in management. For this question to be answered biopsy needs to be obtained for molecular analysis and this is where “blind” biopsies fall short.

Additional Sources

Spritzer CE, Afonso PD, Vinson EN, et al. Bone marrow biopsy: RNA isolation with expression profiling in men with metastatic castration- resistant prostate cancer—factors affecting diagnostic success. Radiology 2013; 269:816–823.

Lorente D, Omlin A, Zafeiriou Z, et al. Castration-resistant prostate cancer tissue acquisition from bone metastases for molecular analyses. Clin Genitourin Cancer 2016; 14:485–493.

Post Author:
Jehan L Shah, MD
Diagnostic Radiology Resident, PGY-4
shahjl@radiology.ufl.edu
University of Florida, Department of Radiology. Gainesville, Florida.

Evaluation of a Device Combining an Inferior Vena Cava Filter and a Central Venous Catheter for Preventing Pulmonary Embolism Among Critically Ill Trauma Patients

Summary

Critically ill trauma patients have elevated risk for pulmonary embolism (PE) due to a combination of immobility, depletion of anti-coagulation factors, and contraindications to anticoagulation (AC) in the setting of hemorrhage. In this population, PE is one of the leading causes of death in patients surviving >1 day. Tapson et al. conducted a prospective multicenter single-arm clinical trial to evaluate the efficacy and safety of a new device, the Angel Catheter (Bio2 Medical) which combines an inferior vena cava filter (IVC) with a central venous catheter. This device received 510(k) clearance from the Food and Drug Administration for use as a short term IVC filter and central venous catheter on 7/28/2016. The filter component is made of nitinol, closed cell in geometry, contains no wall anchoring hooks, and is permanently attached to the 9-F triple-lumen central venous catheter. The enrolled study patients had contraindications to pharmacologic venothromboembolism prophylaxis without or with confirmed lower extremity deep venous thrombosis (DVT) or PE. Between February 2015 and December 2015, 163 intensive care unit patients underwent placement of the Angel catheter, of whom 18/163 (11%) had confirmed proximal lower extremity deep venous thrombosis (DVT) at baseline. For the large majority of patients, device insertion was performed bedside in the ICU, with abdominal radiography to confirm post-deployment filter position between L1-L2 and L4-L5 interspaces. The primary endpoint was freedom from clinically significant pulmonary embolism (PE) 72 hours after device removal or discharge and was achieved in 100% of patients. The Angel catheters were removed in 143 (88%) patients, with the large majority of removals occurring once prophylactic anticoagulation was safely initiated, at a mean of 5.5 hospital days. Notably, 12 (8%) catheters which were removed inadvertently by the patient. Cavograms were performed in 129 patients prior to device removal, of which 31 (24%) showed thrombus in the filter component, including 14 (8.6%) with large clot burden (>25% volume of filter basket) and 17 (10%) with low clot burden (<25% volume of filter basket). These patients with thrombus subsequently underwent anticoagulation therapy and/or placement of a conventional IVC filter. Major bleeding occurred in 5 (3%) of all patients receiving the Angel catheter, and catheter related thrombosis occurred in 20 (12%) cases.



Commentary

Venothromboembolism (VTE) is known to be a major contributor of morbidity and mortality in critically ill trauma patients. Multicenter prospective randomized controlled trials for IVC filters have not included this patient population, but nonrandomized studies have shown decreased rates of PE and PE-related fatalities in patients who receive filters. Although conventional IVC filters may be placed in these patients, studies have demonstrated that the majority of filters are placed late in the ICU course, and therefore the patients may not be adequately protected from PE in their early hospitalization, when they may have contraindications to pharmacologic prophylaxis (reflected in the mean time to initiation of AC of 5.5 days in this study). IVC filters placed in the trauma setting have also been associated with low retrieval rates. The Angel catheter theoretically circumvents both of these pitfalls as a device that may be easily deployed and removed at bedside in the ICU. The results of this study and the European Angel Catheter Registry suggest that this device is both effective for PE prevention and acceptable safety profile in critically ill patients, and may be an exciting addition to the VTE prevention armamentarium in this patient population. As a single arm clinical trial, this study does not offer any comparison to placebo or conventional IVC filter placement, and provides relatively short duration of clinical follow-up, so additional evidence will be needed to elucidate optimal utilization of this device. Because no pre-placement cavography is performed and cross-sectional imaging may not be available in all patients, one could anticipate scenarios in which the Angel catheter could be malpositioned from variant caval or renal vein anatomy and provide suboptimal caval filtration. The relatively high rate of inadvertent catheter dislodgement reported in this study also raises concerns for potential associated morbidity if a filter is pulled out of a vessel without being adequately collapsed in patients not on pharmacology thromboprophylaxis. Despite these limitations, this study provides an important preliminary evaluation of the Angel catheter, which may one day assume a pivotal role in early PE prevention in critically ill patients.

Click here for abstract

Tapson VF, Hazelton JP, Myers J, et al. Evaluation of a Device Combining an Inferior Vena Cava Filter and a Central Venous Catheter for Preventing Pulmonary Embolism Among Critically Ill Trauma Patients. J Vasc Interv Radiol. 2017;28(9):1248-54.

Post Authors:
Jeffrey Forris Beecham Chick, MD, MPH, DABR
Assistant Professor of Vascular and Interventional Radiology
Vice Quality Assurance and Safety Officer
Venous Health Program Faculty
University of Michigan Health System
Michigan Medicine

James X. Chen, MD
Fellow in Interventional Radiology
Hospital of the University of Pennsylvania

From the SIR Residents and Fellows Section (SIRRFS)

Teaching Topic: Outcomes of Ultrasound–Guided Thrombin Injection of Nongroin Arterial Pseudoaneurysms

Valesano JC, Schmitz JJ, Kurup AN, Schmit GD, Moynagh MR, Atwell TD, Lewis BD, Lee RA, Callstrom MR. J Vasc Interv Radiol. 2017 Jun 1. pii: S1051-0443(17)30477-3. doi: 10.1016/j.jvir.2017.05.003. [Epub ahead of print]

Link to Abstract

Arterial pseudoaneurysms are among of the most frequently encountered complications of interventional vascular procedures. Pseudoaneurysms are contained pulsatile hematomas that arise from arterial puncture sites that fail to fully seal. Historically, pseudoaneurysms required surgical vessel closure, though now ultrasound-guided thrombin injection has now become the mainstay first-line treatment. The safety and efficacy of ultrasound-guided thrombin injection for femoral pseudoaneurysms has been well established in large trials and systematic reviews. [1] However, despite the increasing popularity of upper extremity endovascular access, reports of non-groin pseudoaneurysms treatment are limited.

In this study, Valesano et al. at the Mayo Clinic retrospectively review 39 cases of thrombin injection treatment for non-groin pseudoaneurysms. Of these 29 were in the upper extremity and 20 of those were of the brachial artery. Thirty-six were iatrogenic of nature and 22 of those were from arterial access. They report a 100% success rate in achieving zero Doppler flow immediately after thrombin injection and an 84.8% success rate in sustained thrombosis at 1-3 days after treatment

Clinical Pearls

Though there are many techniques, what are the general steps in ultrasound guided thrombin injection?

The authors describe their technique as follows:

1. Obtain baseline arterial duplex US imaging and Dopper waveforms of both the pseudoaneurysms and the origin artery proximal and distal to the site.

2. Evaluate pulses with ultrasound or palpation. Additionally, assess the relevant baseline sensorimotor function.

3. Using sterile technique and 1% lidocaine for anesthesia, advance a 20-25 gauge needle under ultrasound visualization until the tip of the needle is in the pseudoaneurysm sac.

4. Incrementally inject small aliquots of about 100 IU of 1000 IU/1 mL recombinant topical thrombin (The Medicines Company, Parsippany, New Jersey).

5. With intermittent Doppler imaging, monitor the pseudoaneurysm during injection until complete elimination of Doppler signal.

6. Reassess proximal and distal artery with US, pulses, and sensorimotor symptoms.

7. Follow-up imaging with duplex and Doppler US is recommended one day after the procedure.

What are the characteristics of pseudoaneurysms at higher risk of treatment failure?

It is difficult to draw conclusions from the small number of treatment failures from this series, however it appeared that the neck size was more predictive than the total size. The average size of pseudoaneurysms that remained successfully thrombosed at follow up were larger at 2.3cm +/- 1.6, while the average size for treatment failures were 2.0cm +/- 0.7. The neck diameter for treatment failures averaged 2.6 mm +/- 0.5 and 2.1 mm +/- 0.8 for treatment successes. Because of the small sample size, these results trended towards, but did not show statistical significance. Of the treatment failures, three were successfully treated with one retreatment, and the other two were successfully treated after two retreatments.

Questions to Consider

Though the authors reported no complications, what are the potential complications of this procedure?

In the small previous reports, there have been two incidents of brachial artery thrombosis. In 2014, Garvin et al reported 14 cases of treatment with thrombin in the upper extremities. [2] In one of these cases, brachial artery thrombosis was identified by decreased Doppler amplitude distal to the pseudoaneurysm fifteen minutes after treatment. Emergent surgical revascularization was performed. Kang et al reported 5 upper extremity treatments in 2000. [3] In one case, the neck of the pseudoaneurysm persisted after initial thrombin injection, and after a small amount was injected into the residual neck, the patient began to experience symptoms of hand ischemia. Pulses returned and symptoms resided in less than ten minutes after treatment with 5000 IU of heparin.

What special considerations should be taken in patients on anticoagulation therapy?

Successful pseudoaneurysm treatment with thrombin in the setting of concurrent anticoagulation therapy has been well documented for femoral pseudoaneurysms in patients on heparin, warfarin, clopidogrel, and aspirin. [4] While the authors of this study did not report the anticoagulation status of the treated patients, in the previously mentioned study of 14 cases, 9 patients were on anticoagulants for atrial fibrillation. The efficacy in anticoagulated patients compared to ultrasound-guided compression remains one of the leading justifications for thrombin therapy.

Additional Sources

1. Tisi PV, Callam MJ. Treatment for femoral pseudoaneurysms. Cochrane Database Syst Rev. 2013 Nov 29;(11):CD004981. doi: 10.1002/14651858.CD004981.pub4. Review. PMID: 24293322.

2. Garvin RP, Ryer EJ, Yoon HR, Kendrick JB, Neidrick TJ, Elmore JR, Franklin DP. Ultrasound-guided percutaneous thrombin injection of iatrogenic upper extremity pseudoaneurysms. J Vasc Surg. 2014 Jun;59(6):1664-9. doi: 10.1016/j.jvs.2014.01.009. Epub 2014 Feb 20. PMID: 24560862.

3. Kang SS, Labropoulos N, Mansour MA, Michelini M, Filliung D, Baubly MP, Baker WH. Expanded indications for ultrasound-guided thrombin injection of pseudoaneurysms. J Vasc Surg. 2000 Feb;31(2):289-98. PMID: 10664498.

4. Krueger K, Zaehringer M, Strohe D, Stuetzer H, Boecker J, Lackner K. Postcatheterization pseudoaneurysm: results of US-guided percutaneous thrombin injection in 240 patients. Radiology. 2005 Sep;236(3):1104-10. Epub 2005 Jul 29. PubMed PMID: 16055694.

Post Author
Charles Hyman, MS4
Warren Alpert Medical School of Brown University