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Wednesday, April 18, 2018

From the SIR Residents and Fellows Section (SIRRFS)


Teaching Topic: Uterine Artery Embolization for Pedunculated Subserosal Leiomyomas: Evidence of Safety and Efficacy


Kim, YS, Han K, Kim M, Kim GM, Kwon JH, Lee J, Choi W, Won JY, Lee DY. Uterine Artery Embolization for Pedunculated Subserosal Leiomyomas: Evidence of Safety and Efficacy. 2018 Feb 22. doi: 10.1016/j.jvir.2017.11.022 [Epub ahead of print]

Click here for abstract

Uterine artery embolization (UAE), colloquially known as uterine fibroid embolization, has become a widely accepted and increasingly popular option for the treatment of symptomatic leiomyomas. Since its first report by Ravina et al. in 1995, the evidence supporting its safety and efficacy has become increasingly robust with large prospective, randomized controlled trials like the REST and EMMY trials. [1,2] Recently, emerging evidence is even broadening the conditions that UAE could be indicated for to include adenomyosis and premenstrual symptoms. [3] Despite these advances, the historical controversy surrounding UAE for pedunculated subserosal (PS) leiomyomas, particularly ones with narrow stalks, has persisted. Guidelines from the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) list PS leiomyomas with stalks that are less than 50% the diameter of the leiomyoma as a relative contraindication because of the risk of torsion and ischemic necrosis of the stalk and resulting separation of the leiomyoma from the uterus. These concerns largely stem from two early cases where necrotic PS leiomyomas detached and became a source of sepsis which required hysterectomy and bowel resection. [4] Because of this risk, PS leiomyomas were generally excluded from the major UAE trials, including the REST trial. However, the guidelines from the SIR Standards of Practice Committee explicitly refutes this contraindication citing four retrospective series of 12, 16, 18, and 29 patients who underwent successful UAE for PS leiomyomas. [5] In this study, Kim et al. present the largest and most comprehensive series to date of UAE for PS leiomyomas in 55 patients.

In this retrospective review, the authors present 55 patients with a total of 66 PS leiomyomas treated with UAE between 2007 and 2016. They further categorized leiomyomas with stalk diameters 25% or less of the diameter of the leiomyoma as high-risk (n=11) and leiomyomas with stalk diameters 50% or less of the diameter of the leiomyoma low-risk (n=55). Magnetic resonance imaging was performed 3 months after UAE to compare infarction rate and volume reduction between high-risk and low-risk groups and between PS leiomyomas and leiomyomas in other locations. The authors successfully embolized the uterine arteries bilaterally in 54/55 (98.2%) of patients. There was no significant difference in the mean volume of reduction in PS leiomyomas compared to non-PS leiomyomas (38.2% vs 38.4%, p=.953), though the mean infarction rate in PS leiomyomas was significantly lower than the rate in non-PS leiomyomas (86.0% vs 99.9%, p=.0025). All 66 stalks continued to enhance after UAE. Clinically, 53/55 patients reported symptomatic improvement. One of the patients who did not was the aforementioned technical failure due to non-embolized inferior mesenteric artery collaterals. It was not known what prevented symptomatic improvement in the other patient as volume reduction rates were in line with the other patients.
MR images before and after UAE for a high-risk PS leiomyoma showing complete infarction and remaining stalk enhancement. 


Clinical Pearls


What are the different locations of uterine leiomyomas?

Leiomyomas are typically classified by their location. Intramural leiomyomas, the most common type, occur in the muscular wall of the uterus. Subserosal leiomyomas are the rarest form and occur under the uterine serosa on the surface of the uterus. These can be pedunculated or sessile. They typically do not cause infertility. Submucosal leiomyomas occur under the endometrium and also may be pedunculated or sessile. Submucosal leiomyomas have the largest effect on fertility.

What imaging is required before a UAE?

MR imaging is generally performed before and after the procedure to evaluate leiomyoma amount, size, location, presence of adenomyosis and response to treatment. 3D reconstructed MRA imaging can be used for preprocedural planning and mapping of the uterine and ovarian artery and checking for variant anatomy. The authors of this study did not report if they used MRA preprocedurally and had one technical and clinical failure due to a collateral inferior mesenteric artery that was not embolized.

Questions to Consider


What are the potential complications and adverse events of UAE for PS leiomyomas?

In this study, the authors reported no major adverse events and 3 minor adverse events. Two of these consisted of the expulsion of submucosal leiomyomas. The third adverse event was a presentation to the emergency room 2 days after UAE for pelvic pain which resolved after 2 hours. Stalk necrosis causing separation and the subsequent infection is the primary fear with PS leiomyomas. This study compared stalk enhancement to adjacent myometrium and found no difference in enhancement in any of the 66 cases.

What is the evidence level of the SIR recommendation?

According to the 1998, United States Presentative Services Task Force (USPSTF) guidelines on levels of evidence, the recommendations by the SIR Standards of Practice Committee would be considered Level III evidence as it is expert opinion based on descriptive studies. This study adds 55 more patients to the previously documented 75 cases from the four case series. Level II evidence describes recommendations based from cohort, case-control, or non-randomized controlled trials. Recommendations require at least one randomized controlled to be considered Level I.

Additional Citations

1. The Rest investigators (2007) Uterine-artery embolization versus surgery for symptomatic uterine fibroids. N Engl J Med 356:360–370

2. Hehenkamp WJK, Volkers NA, Birnie E, Reekers JA, Ankum WM (2008) Symptomatic uterine fibroids: treatment with uterine artery embolization or hysterectomy. Results from the randomized clinical embolization versus hysterectomy (EMMY) trial. Radiology 246:823–832

3. Jang D, Kim MD, Lee SJ, Kim IJ, Park SI, Won JY, Lee DY. The effect of uterine artery embolization on premenstrual symptoms in patients with symptomatic fibroids or adenomyosis. J Vasc Interv Radiol. 2014 Jun;25(6):833-838.e1. doi:10.1016/j.jvir.2014.01.036. Epub 2014 Mar 20. PubMed PMID: 24657088.

4. Braude, P., Reidy, J., Nott, V., Taylor, A., and Forman, R. Embolization of uterine leiomyomata: current concepts in management. Hum Reprod Update. 2000; 6: 603–608

5. Dariushnia, S.R., Nikolic, B., Stokes, L.S., and Spies, J.B. Quality improvement guidelines for uterine artery embolization for symptomatic leiomyomata. J Vasc Interv Radiol. 2014; 25: 1737–1747

Post Author:
Charles Hyman, MS4
Chair, Communications Committee, SIRRFS
Warren Alpert Medical School of Brown University

Friday, April 13, 2018

Embolization for RCC: shift in treatment paradigm?


Summary


Researchers from Karolinska University Hospital in Stockholm have recently published their results of a prospective controlled trial on renal cell carcinoma (RCC) embolization. RCC is typically managed through nephron-sparing surgery, radical nephrectomy, ablation, or active surveillance. In this manuscript, the authors compared doxorubicin eluting embolic (DEE) to bland TAE. A total of 12 patients with average tumor size of 3.2 cm +/- 0.62 were randomized to receive DEE or TAE before a planned surgery. Size of embolic was determined on basis of degree of vascularity and ranged from 75-150 micron, 100-300 micron, and 300-500 micron. A CT was performed prior to surgical removal to assess treatment response. DEE transarterial chemoembolization (n = 6) resulted in a significantly (P = .018) higher degree of necrosis with an average of 88.3% compared with TAE (n = 5), which resulted in an average of 29.4%, as evaluated by CT. Histopathologic evaluation showed similar results (P = .016) with an average necrosis of 87.5% for DEE transarterial chemoembolization (n = 4) versus 26% for TAE (n = 5). Percentage of necrosis seen on microscopy correlated significantly (P = .0005) with radiologic findings, as 4 tumors in each arm were evaluated by both CT and microscopy. No major complications were observed in either group. The authors concluded that TACE is safe to be performed for localized RCC and has a significantly superior effect when compared with TAE.
Images of RCC treated by transarterial chemoembolization in patient 12. (a) Subtraction angiography image obtained after selective catheterization of the left renal artery showed contrast-filled intratumoral vessels (arrowhead) before transarterial chemoembolization. (b)Subtraction angiography image obtained during transarterial chemoembolization showed no contrast-filled vessels in the center of the tumor owing to ongoing embolization. The area adjacent to RCC (arrowhead) shares its blood supply with the tumor. (c) CT imageobtained before transarterial chemoembolization showed contrast enhancement in RCC (arrowhead). (d) CT image obtained 4 weeks after transarterial chemoembolization showed no contrast enhancement in RCC (arrowhead). Infarcted renal tissue (arrow) is adjacent to the treated tumor.

Commentary


This manuscript is noteworthy as it opens the avenue for more catheter-based research for RCC locoregional treatment. The authors were able to demonstrate a statistically significant increased response to doxorubicin DEB compared to bland embolic. While both embolics contained residual tumor on pathologic evaluation, DEB had significantly better tumor response. This is interesting as systemic doxorubicin is not known to have a significant impact on RCC. Further, many tumors can become resistant to the effects of doxorubicin when they are ischemic (as with embolization). Clearly, there is more happening at the tumor level than we currently understand. However, is this all a moot point given the current treatment paradigm in RCC? There is a relatively low likelihood that a patient would not be a candidate for partial nephrectomy or ablation and have a tumor undergoing rapid enough growth to require palliative treatment. As such, this manuscript may be more impactful in what it says about the local effects of embolization and image-guided drug delivery and is unlikely to change RCC treatment algorithms.

Click here for abstract

Karalli A, Ghaffarpour R, Axelsson R, Lundell L, Bozoki B, Brismar T, Gustafsson O. Transarterial Chemoembolization of Renal Cell Carcinoma: A Prospective Controlled Trial. J Vasc Interv Radiol. 2018; 12:1664-1672

Post Author:
Luke R. Wilkins, MD
Assistant Professor
Department of Radiology and Medical Imaging
Section of Vascular and Interventional Radiology
University of Virginia
@LukeWilkins_UVA

Thursday, March 29, 2018

From the SIR Residents and Fellows Section (SIRRFS)


Teaching Topic: Value of Antibiotic Prophylaxis for Percutaneous Gastrostomy: A Double-Blind Randomized Trial


Ingraham CR, Johnson G, Albrecht EL, et al. Value of antibiotic prophylaxis for percutaneous gastrostomy: a double-blind randomized trial. J Vasc Interv Radiol. 2018; 29: 55-61.



Since its development in 1980, percutaneous radiologic gastrostomy (PRG), also known as radiologically inserted gastrostomy (RIG) or simply percutaneous gastrostomy (PG), has become a common, safe, and effective option for the delivery of nutritional support to treat or prevent malnutrition in patients where oral intake is contraindicated. While surgical gastrostomy, performed endoscopically, known as percutaneous endoscopic gastrostomy (PEG), is the traditional gold standard, there are many advantages for fluoroscopically placed gastrostomy. In a meta-analysis, radiologic gastrostomy had a higher rate of successful placement than surgical (99.2% vs. 95.7%, p < .001) with a reduced major complication rate (5.9% vs. 9.4%, p <.001). [1] Additionally, radiological placement does not require general sedation and can avoid passage through the oropharynx preventing tumor seeding in head and neck cancer cases. Likewise, the avoidance of the oral passage and the prevention of contamination with oral flora is frequently cited as a major benefit of radiological placement. [2,3] In this study, Dr. Ingraham et al. conducted a double-blinded, randomized controlled trial to compare peristomal infection rates after prophylactic antibiotics in percutaneous gastrostomy.

The guidelines from the SIR Standards and Practice Committee recommends routine administration of prophylactic antibiotics in “pull technique” gastrostomy tube placement (transoral access), but did not find a consensus for prophylaxis administration with the “push technique” (transabdominal access). This study measured the rates of peristomal infection in 122 patients who received push-type gastrostomy placement in three study arms- placebo (n=34), prophylactic antibiotic administration (n=34), or in an observational group if they were already receiving antibiotics for another indication (n=68). All patients received a 16-F Deutsch gastrostomy tube (Cook Medical, Bloomington, Indiana), a pigtail catheter, placed over a stiff wire through an 18-gauge needle centered within 3 absorbable gastropexy sutures. Patients in the treatment arm received 1 g of intravenous cefazolin or 600 mg of intravenous clindamycin in those with allergies. A blinded evaluator examined the stoma site for subjective signs of infection at 3-5 days, 7-10 days, 14-17 days, and 28-30 days.

Because patients were lost to follow up or started on antibiotics for unrelated infections, analysis was restricted to the early time period (<10 days). During this period, 4/34 (11.8%) patients in the placebo arm and 0/34 (0.0%) in the treatment arm were found to have stoma site infections. This trend was not found to be statistically significant under intention-to-treat analysis (p = .057). However, under per-protocol analysis the difference between infection rate of 4/30 (13.3%) patients in the placebo arm and the 0/32 (0.0%) in the treatment arm was statistically significant (p=.049). Only one patient was found to have an infection in the observation arm, but compared to the placebo this difference was not significant in intention to treat (p=.078) or per protocol (p=.063) analysis.




Clinical Pearls


How can you tell if a stoma site is infected? How common is stoma site infections?

The authors of this study used an 11-point scale based on erythema, induration, and exudate that was originally developed for studying antibiotic prophylaxis in PEG placement. The points were distributed based on the “presence of erythema (0, none; 1, ≤ 5 mm; 2, 6–10 mm; 3, 11–15 mm; 4, ≥ 15 mm), induration (0, none; 1, ≤ 10 mm; 2, 11–20 mm; 3, ≥ 20 mm), and exudate (0, none; 1, small serous; 2, moderate serous; 3, large serous ± sanguineous; 4, purulent).”

According to the review of the literature in the SIR Antibiotic Prophylaxis guidelines, infections in transoral access range from 4%-30%, but infections in retrospective series of transabdominal access without antibiotics ranged from 0-2%. [4,5]. However, a retrospective review of head and neck cancer patients who underwent transabdominal gastrostomy found 15% infection rate among the patients that were not treated with prophylaxis. [6] Patients with head and neck cancer were not excluded from the study discussed in this Teaching Topic- 9 patients received placebo, 8 received treatment, and 15 were in the observation arm. It is possible this played a part in the relatively high (11.8-13.3%) infection rate found in this study.

What is the difference between the methods of radiologic gastrostomy?

While the SIR antibiotic guidelines only differentiate between the “push” and “pull” methods, there are many different variations on fluoroscopically placed gastrostomy tubes. For antibiotic consideration, traversing the oral cavity is likely the biggest consideration.

The classical radiologically inserted gastrostomy is a Seldinger technique that consists of insufflating the stomach through a nasogastric tube then percutaneously passing a needle into the stomach. A wire is then passed and a gastrostomy tube is then passed over the wire. This technique was first described in 1981 by Preshaw and modified to include percutaneous gastropexy by Brown et al. in 1986. [7,8] This is called the “push” method as you push the gastrostomy tube percutaneously into the stomach.

Transoral access allows for larger tube sizes, the same as placed endoscopically. This method utilizes a similar technique to enter the stomach before passing a catheter retrograde through the esophagus and out the oral cavity where a gastrostomy tube is advanced over the wire. This is what is referred to as the “pull” method as you pull the gastrostomy tube out of the stomach into its final position. It is standard of care to give antibiotics with this method.

Questions to Consider:


What is the difference between intention-to-treat and per protocol analysis?

Intention to treat (ITT) and per protocol are different methods for analyzing results of randomized controlled trials. ITT includes all subjects as originally randomized, regardless of completion of treatment, to compare outcomes of the groups. Per protocol only includes subjects who completed treatment and outcome assessment. ITT reduces the possible bias if attrition, non-compliance, or protocol mistakes were non-random. Broadly speaking, ITT measures the efficacy of the treatment protocol, while per protocol measures the outcomes of the specific treatment. In this study, patients were given antibiotics for other infections, thus violating the protocol and introducing a possible bias. These patients were excluded from the per protocol analysis which was found to be statistically significant. It is important to consider both ITT and per protocol when making clinical decisions based on trial data.

Additional Sources:

1. Wollman B, D’Agostino HB, Walus-Wigle JR, Easter DW, Beale A. Radiologic, endoscopic, and surgical gastrostomy: an institutional evaluation and meta-analysis of the literature. Radiology. 1995;197(3):699–704.

2. Shin JH, Park A-W. Updates on percutaneous radiologic gastrostomy/gastrojejunostomy and jejunostomy. Gut Liver. 2010;4(Suppl 1):S25–31.

3. Sutcliffe, J, Wigham, A, Mceniff, N, Dvorak P, Uberoi R. CIRSE Standards of Practice Guidelines on Gastrostomy. Cardiovasc Intervent Radiol. 2016;39(7):973.

4. Venkatesan, A.M., Kundu, S., Sacks, D. et al. Practice guidelines for adult antibiotic prophylaxis during vascular and interventional radiology procedures. Written by the Standards of Practice Committee for the Society of Interventional Radiology and Endorsed by the Cardiovascular Interventional Radiological Society of Europe and Canadian Interventional Radiology Association [corrected]. J Vasc Interv Radiol. 2010; 21: 1611–1630

5. Wollman, B. and D’Agostino, H.B. Percutaneous radiologic and endoscopic gastrostomy: a 3-year institutional analysis of procedure performance. AJR Am J Roentgenol. 1997; 169: 1551–1553

6. Cantwell, C.P., Perumpillichira, J.J., Maher, M.M. et al. Antibiotic prophylaxis for percutaneous radiologic gastrostomy and gastrojejunostomy insertion in outpatients with head and neck cancer. J Vasc Interv Radiol. 2008; 19: 571–575

7. Preshaw RM. A percutaneous method for inserting a feeding gastrostomy tube. Surg Gynecol Obstet. 1981;152(5):658–60.

8. Brown AS, Mueller PR, Ferrucci JT. Controlled percutaneous gastrostomy: nylon T-fastener for fixation of the anterior gastric wall. Radiology. 1986;158(2):543–5.

Post Author:
Charles Hyman, MS4
Chair, Communications Committee, SIRRFS
Warren Alpert Medical School of Brown University

Friday, March 23, 2018

Embolization for Relief of Chronic Shoulder or Elbow Pain 


Summary


A recent study from researchers at the Konkuk University School of Medicine in Seoul, Korea have published their findings on embolization for relief of chronic shoulder or elbow pain associated with tendinopathy refractory to conservative treatment. The study included 13 patients (15 procedures) and involved 8 shoulders and 7 elbows. The elbow pain was due to lateral epicondylitis and the shoulder pain was secondary to rotator-cuff tendinopathy (n=6) and calcific tendinitis (n=2). The researchers used microspheres (40-120 micron) in the first 4 cases and imipenem/cilastatin sodium(mixed with lipiodol) in the remaining 11. Technical success was seen in all patients with clinical success in 73% (11 of 15). Among the 12 patients with pain relief, 7 patients (58%) experienced pain relief within 1 week and 9 (75%) experienced pain relief within 1 month. The remaining 3 cases experienced pain relief between 1-4 months post embolization. Authors noted that when a patient had “evident” enhancement, 90% of them had clinical success. However, 60% (3 of 5) had success when there was not evident enhancement. There were no major adverse events. Self-limited forearm erythema was noted in 1 patient that resolved within 1 month. The authors conclude that embolization may be an option for pain relief associated with chronic shoulder and elbow tendinopathy.



Fig 2. Left brachial arteriographic imaging before and after transcatheter arterial embolization with microspheres in a 48-year-old woman (patient 2; Table) with chronic elbow pain (7 mo) as a result of lateral epicondylitis. (a)Preembolization arteriography shows evident enhancement (white arrows) fed by the recurrent radial artery (black arrows) in a region adjacent to the lateral epicondyle. (b) Postembolization arteriography shows disappearance of hyperenhancement adjacent to the lateral epicondyle. At 4-month follow-up, the patient continued the pretreatment medication regimen despite a reduction in VAS score from 5 to 2.

Commentary


This paper presents a new and innovative treatment approach to chronic shoulder and elbow pain. There has been previous literature suggesting that embolization may be beneficial for adhesive caposulitis and knee osteoarthritis. Tendinopathy is a costly medical condition that has multiple treatment options that are frequently refractory to treatment. As such, an alternative treatment approach may have widespread use and applicability. Neovessels and accompanying nerves have been identified as possible sources of inflammation and pain in this setting. The present study shows promising results in embolization of this neovascularity as a treatment method. As detailed above, identifying “evident” enhancement increased the chances of clinical success. VAS scores in the evident enhancement group were decreased more (P < .05) than those in the group with no evident enhancement. These results suggest that the degree of lesion enhancement on DSA might be a factor to predict the degree of pain relief after embolization. Of note, IPM/CS has been approved by the FDA as an antibiotic. It is slightly soluble in water but will crystallize when mixed with a contrast agent and create 10-70 micron size particles. Previous literature has shown this embolic to be associated with decreased rates of cutaneous erythema. Limitations of this manuscript include the small number of patients, retrospective nature, short follow-up (4 months), lack of standard embolic use, and non-standard post-procedure pain control. However, within these limitations, the future of this therapy appears promising and future trials are warranted. This manuscript further proves that there is no vascular territory that we will not embolize.

Click here for abstract

Hwang JH, Park SW, Kim KH, et al. Early Results of Transcatheter Arterial Embolization for Relief of Chronic Shoulder or Elbow Pain Associated with Tendinopathy Refractory to Conservative Treatment. J Vasc Interv Radiol. 2018; 29: 510-517.

Post Author:
Luke R. Wilkins, MD
Assistant Professor
Department of Radiology and Medical Imaging
Section of Vascular and Interventional Radiology
University of Virginia
@LukeWilkins_UVA

Tuesday, January 9, 2018

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.



Monday, September 11, 2017

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

Monday, July 31, 2017

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]


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