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.

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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

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.

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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

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.