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Monday, September 17, 2018

Clinical Predictors of Port Infections in Adult Patients with Hematologic Malignancies


Summary


Infection is typically the most common long-term complication of port placement and is also the most common reason for premature removal of a port. In addition, patients with hematologic malignancies have been reported to have a higher risk of port infection relative to the solid tumor population. In this paper, the authors performed a single center retrospective review of 223 patients with hematologic malignancies who underwent port placement for chemotherapy. Prophylactic antibiotics were administered to every patient. Identification of risk factors for port infection were assessed by stratifying patients based on demographics, clinical history, medications, type of malignancy, port characteristics, and a host of laboratory values. The definition of infection was also specified according to CDC guidelines as early infection and overall infection. Early infection was defined as that occurring within 30 days of placement.

A total of 8 out of 223 (3.6%) patients had early infection. During the follow-up period 26 patients (11.7%) overall had port infections. After inclusion of variables into the final regression model, hypoalbuminemia at the time of port placement was the only independent risk factor for early port infection (p=.03). Lab values at the time of port placement were not analyzed in the context of overall infection. From a medication standpoint, steroid therapy was the only independent risk factor associated with port infection in the overall infection group (p=.002).





Table 5, 6. ALL = acute lymphocytic leukemia; AML = acute myelogenous leukemia; BMI = body mass index; CI = confidence interval; CLL = chronic lymphocytic leukemia; HR = hazard ratio; NA = nonapplicable owing to small number of patients within the subgroup; PSHREG = proportional subdistribution hazard regression.
Incorporated in multivariate logistic regression.
Significance at .05 level.


Commentary


This article is elegant in its simplicity and ability to identify potentially implementable screening practice parameters. More than any other complication, infection tends to be the most perseverated upon in regards to port placements. This is even more paramount for patients with hematologic malignancies who will likely suffer severe leukopenia after initiation of chemotherapy. The results of this study suggest that initiation of pre-procedural screening for patients with hypoalbuminemic states may prove beneficial in minimizing early port infections although further prospective randomized trials may be needed. On the contrary, steroids were frequently (though not always) a component of chemotherapy regimens in this study and are likely non-modifiable parameters to minimize port infections. Port placements in these patients are an absolute necessity and delaying placement to discontinue steroid therapy is probably not in their best interest. These decisions will likely need to be made on a case by case basis. However, a concerted effort to improve nutrition and potentially increase albumin levels is an easily modifiable and low/no risk intervention that is probably overlooked in its significance.

Click here for abstract

Shunqing Zhang, MS, Katsuhiro Kobayashi, MD, Masoud Faridnia, MD, Philip Skummer, MPH, Dianbo Zhang, MD, Mitchel I. Karmel, MD. Clinical Predictors of Port Infections in Adult Patients with Hematologic Malignancies. J Vasc Interv Radiol 2018; 29: 1148-1155.

Post Author:
Cane Hoffman, MD, PGY-5
Department of Radiology
Wake Forest Baptist Medical Center
@WakeForest_IR

Thursday, September 13, 2018

Prostatic Artery Embolization with 250-μm Spherical Polyzene-Coated Hydrogel Microspheres for Lower Urinary Tract Symptoms with Follow-up MR Imaging


Summary


Investigators from the University of Jena, Germany, published their initial experience of prostatic artery embolization (PAE) with 250-μm spherical, Polyzene-coated hydrogel microspheres with a diameter of 250 μm (Embozene; Boston Scientific). 30 patients with moderate to severe lower urinary tract symptoms were included in this prospective, nonrandomized study. Clinical outcomes and possible MR imaging predictors of clinical success were analyzed. PAE was technically successful in 90% of patients (who had at least unilateral embolization). Clinical success measured by decreased IPSS and QOL scores and increased Qmax were accomplished in 59% (16 of 27), 63% (17 of 27), and 74% (20 of 27) after 1, 3, and 6 mo, respectively. IIEF scores did not differ significantly during follow-up. Adverse events included urethral burning (5 of 27), fever (2 of 27), and urethral bleeding, rectal bleeding, cystitis, and penile burning sensation (1 of 27 each). No initial MR imaging changes correlated statistically with clinical outcomes after 6 months (P values from .14 to .98). The authors concluded that PAE with 250-μm hydrogel microspheres led to good clinical success after 6 months with a low complication rate and MR imaging predictors of clinical success were not identified.



Figure. (a) Posterior–anterior view of the left hemiprostate after application of contrast material. The microcatheter is placed above the bifurcation of the left prostatic artery into a central branch (vertical arrow) and a lateral branch (horizontal arrow). (b) Image after PAE with 250-μm microspheres.

Commentary


This manuscript presents the results of a specific embolic agent, 250um Polyzene-coated hydrogel microspheres (Embozene; Boston Scientific), on PAE performed in a limited cohort of patients with symptomatic BPH. Effectiveness and safety results were comparable to the current literature. As PAE is becoming a common therapeutic approach in this patient population, the question of which embolic agent is the most appropriate starts to emerge. Recent meta-analysis including studies that used different types of particulate agents showed better clinical outcomes with smaller PVA (50-100um). However, to better answer this question large randomized control trials would be required. For now any additional evidence on different agents are welcomed to help interventionalists decide which material to use. Finally, defining predictor factors for better clinical outcomes on imaging can be extremely helpful, but this was not possible in the present study likely due to the small sample size, which is a limitation. Further investigation could aim to define predictor factors on pre-procedure imaging. These potential findings could really impact the decision making process and clinical management.

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Franiel T, Aschenbach R, Trupp S, et al. Prostatic artery embolization with 250-μm spherical polyzene-coated hydrogel microspheres for lower urinary tract symptoms with follow-up MR imaging. J Vasc Interv Radiol. 2018; 29: 1127-1137.

Post Author:
Ricardo Yamada, MD
Assistant Professor
Department of Radiology
Division of Vascular and Interventional Radiology
Medical University of South Carolina

Monday, September 10, 2018

Chemoembolization with Vascular Disrupting Agent CKD-516 Dissolved in Ethiodized Oil in Combination with Doxorubicin: A VX2 Tumor Model study


Summary


The authors report the findings of a translational study using a Rabbit squamous cell tumor model implanted into the left hepatic lobe. The authors sought out to evaluate the necrotic and toxic effects of CDK-516, which is a Vascular Disrupting agent (VDA). VDA’s work by disrupting immature and proliferating endothelial cells by inducing apoptosis and breakdown of the cytoskeleton. Ten rabbits where allocated into each of the 4 different groups: Lipiodol alone, Lipiodol+ CDK-516, Lipiodol + Doxorubicin, Lipiodol + CDK-516+Doxorubicin. The chemotherapeutic regimen was then injected into the left hepatic artery. Post embolization non-contrast CT was obtained to evaluated lipiodol deposition. The authors then evaluated AST and ALT levels at day 1, 3 and 7. On day 7 the rabbit was sacrificed and histologic analysis was performed by evaluating percent of tumor necrosis in the histologic slide that presented the largest portion of tumor. Ischemic changes were also evaluated on the gross specimen.

The authors found 47.1% tumor viability in group A, 27.5% in group B, 14.4% in group C and 0.7% in group D. There was a statistical difference between the 4 groups, as well as when pairwise comparisons were performed. On gross specimen evaluation there was 0% infarction rate in group A, 20% in group B, 40% in group C and 80% in group D. AST and ALT levels showed significant differences on days 1 and 3, and between group B and D on days 1, 3 and 7.

It is important to highlight that VDAs and antiangiogenic agents such as Sorafenib VDAs target established tumor vascularity that results in ischemia and necrosis in the tumor center, while Sorafenib targets new vessel formation around the tumor. The reason for which CKD-516 infusion leads to central tumor necrosis is that it targets immature tumor vessels by targeting microtubules, which deprive the tumor from oxygen and nutrients. In the tumor periphery there are immature tumor vessels and normal vessels therefore CKD-516 does not work effectively which leads to tumor survival in the periphery. Therefore, the combination of cytotoxic agents (Doxorubicin) and VDAs would seem to offer a synergistic effect where both the tumor center and periphery are treated. On the other hand, CKD-516 also showed ischemic and toxic effects as seen by the 80% gross parenchymal infarction seen in group D and the elevation in AST and ALT which did not normalize to control level. The reason for this, the authors postulate, is that systemic doses were administered intra-arterially, which may be potentially a large dose for intra-arterial injection.

The authors identified important limitations. The adequate dosage for CKD-516 is unknown. The combination strategy of CKD-516 and doxorubicin is theoretical, however actual synergy and drug interaction between the agents has not been studied. The histologic evaluations were performed without blinding which may introduce bias. Toxicity was only evaluated by studying elevation of AST and ALT and gross pathologic inspection. VX2 tumors are squamous cell tumors that present a natural course of central necrosis. And finally, tumor necrosis assessment was done by evaluating the section with the largest tumor area, instead of a volumetric analysis.

The authors concluded that the intra-arterial injection of CKD-516 and Doxorubicin showed a therapeutic benefit in a rabbit liver tumor model, and that future studies need to be undertaken to optimize the pharmacologic characteristics of the regimen so that it can eventually be used in clinical trials.



Figure- Histopathologic analysis of the 4 groups. Areas of necrosis are marked by *, tumor area is delineated by the arrows. # denotes necrosis in the adjacent liver parenchyma.

Commentary


This manuscript draws a strong argument for the use of combination therapy in targeting different pathways in the treatment of liver tumors. By using cytotoxic agents and VDAs, tumors are not only treated by inhibiting tumor growth in the periphery (Doxorubicin) but also the tumor center (CKD-516). As the authors adequately identified, there are important differences between the rabbit liver tumor model and human HCC. Therefore, definitive assumptions cannot be made, however this is a step forward in creating stronger regimens that maybe be treated with catheter directed techniques. Important studies need to follow, such as adequate dosage evaluation, pharmacokinetics, drug interaction and toxicity. As it stands, the synergistic effect of these two drugs appear to lead to high tumor necrosis (0.7% tumor viability) and high toxicity (80% ischemic changes), therefore studies are required to identify the dosage that will allow high tumor necrosis and minimize the toxic side effects.

Click here for abstract

Lee IJ, Lee M, Kim SJ, Kim YK, Won JY, Chung JW. Chemoembolization with Vascular Disrupting Agent CKD-516 Dissolved in Ethiodized Oil in Combination with Doxorubicin: A VX2 Tumor Model Study. J Vasc Interv Radiol. 2018 Aug;29(8):1078-1084. doi: 10.1016/j.jvir.2018.03.016. Epub 2018 Jun 15. PubMed PMID: 29910164.

Post Author
Carlos J. Guevara, MD
Assistant Professor
Department of Radiology, Interventional Radiology Division
University of Texas Health Sciences, Houston
@UTHouston_IR
@CarlosGuevaraIR

Thursday, September 6, 2018

Anatomic Recanalization of Hepatic Vein and Inferior Vena Cava versus Direct Intrahepatic Portosystemic Shunt Creation in Budd-Chiari Syndrome: Overall Outcome and Midterm Transplant-Free Survival


Summary


Budd Chiari Syndrome (BCS) is a rare, devastating and potentially life-threatening condition related to significant hepatic venous outflow compromise. There are few studies that have robustly reviewed and compared outcomes of active interventions to reverse or by pass the underlying anatomical manifestation of the problem. Interventional radiology has been the lynch pin of these interventions.

Researchers from Institute of Liver and Biliary Sciences, D-1, Vasant Kunj in New Delhi, India recently published their clinical outcomes data for patients with BCS receiving either hepatic/inferior vena cava venous recanalization or DIPS (Direct intrahepatic porto-systemic shunt).

The retrospective study included 136 patients (92 venous recanalization and 44 DIPS) receiving endovascular treatment option based on a clearly defined clinical algorithm. They objectively evaluated Liver US elastography, biochemical markers, imaging pre and post intervention at defined periods. Patients were all followed up until either liver transplantation, death or last clinical visit prior to the end of the study period. In those patients with symptom recurrence and evidence of in-stent stenosis on imaging there was reintervention.

Both groups demonstrated significant clinical, biochemical and liver stiffness (elastography) improvement with intervention. There were lower number of reinterventions in the recanalization group (4%) vs DIPS group (7%) with the later attributed to mainly poor compliance to anticoagulation therapy.

There were no significant differences in the transplant free survival and overall survival between the two groups. The consistent predictor of death and poor clinical outcome in both groups was initial presentation in acute fulminant liver failure with encephalopathy, regardless of successful outflow restoration. They concluded that although DIPS was successful in flow restoration in that cohort, it needed to be considered carefully due to risk of exacerbating encephalopathy and those patients would be best served with liver transplant.



Commentary


The study adds to a growing body of evidence of the usefulness and durability of endovascular intervention in managing this rare but debilitating condition – BCS. The authors findings are largely consistent with the findings of other previous publications which had smaller samples hence adding further validity to the role of endovascular intervention.

One of the remarkable aspects about this study is the unique volume of cases (180 in 4 yrs) from this single institution for a generally uncommon condition - which emphasizes the level of experience and expertise with BCS from this institution. We learn from their experience and expertise that recanalization, wherever possible should be the primary endovascular approach vs DIPS/TIPS first approach. Not only does recanalization provide early treatment success; it is durable, has similar survival benefit to DIPS/TIPS and yet less risk of exacerbation or causing encephalopathy which is generally associated with poor outcomes. We also learn that patients presenting in acute fulminant BCS have a very poor prognosis and concerted efforts should be made towards early liver transplantation.

We also learn that biochemical changes and liver elastography changes appear to be closely linked to clinical improvement in the early period (< 3 months) and therefore could be useful surrogate markers of progress during the early post treatment phase. It is interesting to note that the etiology of the prothrombotic state appeared to not have a bearing on the outcomes of endovascular intervention. Although this may be a true finding, the sample may not be adequately powered to demonstrate that difference.

The study has a number of weaknesses which the authors acknowledge and discuss very well: Retrospective, likely operator bias in selecting patients for DIPS vs recanalization, regional variation in disease process hence variation in US elastography measurements and they do not have very long term follow up. Despite these limitations, the study contributes immensely to the growing evidence about the crucial role interventional radiology plays in the management of BCS.

With the other recently published studies on this issue about the role of IR in the management of BCS, it may be an opportunity for a pooled systematic review on this subject.

Click here for abstract

Mukund A, Mittal K, Mondal A, Sarin SK. Anatomic Recanalization of Hepatic Vein and Inferior Vena Cava versus Direct Intrahepatic Portosystemic Shunt Creation in Budd-Chiari Syndrome: Overall Outcome and Midterm Transplant-Free Survival. J Vasc Interv Radiol. 2018 Jun;29(6):790-799. doi:10.1016/j.jvir.2018.01.781. Epub 2018 Apr 25. PubMed PMID: 29705227.

Post Author:
Rodrick C Zvavanjanja MD, MSc, FRCR, DABR(VIR/DR)
Assistant Professor
Department of Diagnostic and Interventional Radiology
University of Texas at Houston McGovern Medical School
@RodZvavanjanja

Monday, September 3, 2018

Predicting treatment response for transarterial embolization in HCC by analyzing intraprocedural parenchymal blood volume 


Summary


It is difficult to predict which patients with hepatocellular carcinoma (HCC) will have optimal response to transarterial chemoembolization (TACE). While techniques for embolic delivery have evolved over time, identification of tumor factors allowing for quantification of the efficacy of the embolization procedure has not yet been realized. This study evaluated parenchymal blood volume (PBV) before and after embolization as a predictor of angiographic response to TACE of HCC. The authors reasoned that fluoroscopic-cone beam CT could provide semiquantitative assessment of tumoral vascular capacitance through the measurement of PBV. They looked at 40 consecutive patients who had a total of 52 tumors. 33 patients underwent embolization with drug-eluting microspheres, 6 patients underwent conventional chemoembolization, and 1 patient underwent bland embolization. PBV cone-beam CT was performed from the same catheter in the same position before and after embolization. Size measurements were obtained from preprocedural liver CT and tumor response to treatment assessed per mRECIST on posttreatment liver CT performed 3 months after embolization. Embolization was performed to the endpoint of angiographic stasis in all patients. Per mRECIST, 25 tumors (48%) exhibited complete response (CR), 13 (25%) exhibited partial response (PR), 3 (6%) exhibited stable disease (SD), and 11 (21%) exhibited progressive disease (PD). The greatest change in PBV was found in tumors that exhibited CR (200 mL/100 mL ± 99; P = .001) or PR (240 mL/100 mL ± 370; P = .003) to treatment on follow-up imaging. The tumors with lower change in PBVs exhibited SD (64mL/100mL±99;P= .30) or PD (88mL/100mL± 129; P = .06).



Commentary


This study addresses a vital question. How do we know how well a patient with HCC will respond to transarterial embolization? The authors show that change in PBV correlates to the level of response to treatment as seen on 3 month follow up. While these results may not immediately impact practice pattern or fundamentally change the method of TACE in the near-term, the assesment of dynamic changes in tumor perfusion intraprocedurally may help identify tumors that are unlikely to respond to traditional angiographic endpoints of stasis. Identifying these patients at the time of TACE would indicate which tumors are most likely to benefit from embolization adjuncts (balloon-occlusion delivery, antireflux catheters, etc.). The authors acknowledge limitations, including factors relating to generating and processing PBV maps, artifacts, and generalizability to the larger HCC population. However, this data is important to our understanding of HCC and lays the groundwork for further studies aimed at optimizing both assessment of prognosis and treatment.

Click here for abstract

De Korompay N, Alshammari M, Klass D, Chou FY, Chung J, Ho S, Liu DM. Intraprocedural parenchymal blood volume is a predictor of treatment response for chemoembolization in hepatocellular carcinoma: results of a prospective study. J Vasc Interv Radiol. 2018; 29: 928-935.

Post Author:
Zagum Bhatti, MD
Assistant Professor
Department of Radiology, Interventional Radiology Division
University of Texas Health Science Center at Houston, Houston, TX
@UTHouston_IR
@ZagumBhatti

Thursday, August 30, 2018

Comparison of Ultrasound-Accelerated versus Pigtail Catheter-Directed Thrombolysis for the Treatment of Acute Massive and Submassive Pulmonary Embolism 


Summary


This retrospective study expounds on the use of catheter directed lytic therapy in the setting of submassive and massive pulmonary embolism. Its specific aim is to directly compare the effectiveness of ultrasound-accelerated therapy (USAT) to that of nonselective flush catheter (PCDT) thrombolytic infusions. The authors reviewed 101 treatments over a 7 year period, and after exclusion criteria, included 60 treatments in 59 patients, 24 of whom received USAT and 36 of whom received PCDT. Demographics of the two cohorts were similar. Therapy selection was at the discretion of the performing physician, as was thrombolytic dosing and duration. The results demonstrated similar effectiveness of the two techniques, as demonstrated by improved pulmonary artery pressures and Miller index scores (angiographic thrombus scoring system). Placement of the pigtail catheters compared to the USAT catheters took significantly less procedure and fluoroscopy time. There was a nonsignificant trend towards PCDT taking longer, requiring more procedural revisits, and consequently, resulting in an increase in total lytic therapy. However, when normalizing to the first revisit, these trends were no longer observed. There were a total of three 30-day mortalities, only one of which could be directly attributed to lytic therapy. The authors conclude that the clinical efficacy and safety of these two CDT techniques is similar, with the PCDT taking less time to initiate.



Table 3. Reduction in Parameters between Procedures within Groups

Commentary


There has been significant interest in the use of catheter directed therapy (CDT) in the setting of both massive and submassive pulmonary embolism. An increasing body of literature advocates for the use of CDT in both massive and submassive PE. Both patient populations have seen avoidance of hemodynamic collapse, improved PA pressures, decreased thrombus burden, and improved RV function after use of lytic therapy. However, there is little clinical evidence to guide the best technique for administration of this lytic therapy. This paper attempts to shed insight on this matter by comparing USAT to PCDT in a retrospective fashion at a single center. Prior in vivo research has suggested that flow dynamics in the setting of obstruction require infusions to be imbedded in the obstruction for appropriate medication instillation. However, the clinical applicability of this research is not well known. Certainly, USAT has demonstrated effectiveness to lyse thrombus, and some have shown it also to allow a smaller amount of lytic to be administered over a shorter period of time. However, the current study would argue against this literature when applied to routine clinical practice, especially given the similar outcome endpoints, decreases in procedural complexity, and decreased procedure times.

Click here for abstract

Graif A, Grilli CJ, Kimbiris, G et al. Comparison of Ultrasound-Accelerated versus Pigtail Catheter-Directed Thrombolysis for the Treatment of Acute Massive and Submassive Pulmonary Embolism. J Vasc Interv Radiol. 2017; 28(10): 1339-1347.

Post Author:
Daniel P. Sheeran, MD
Assistant Professor
Department of Radiology and Medical Imaging
Division of Vascular and Interventional Radiology
University of Virginia


Monday, August 27, 2018

Analysis of Preoperative Portal Vein Embolization Outcomes in Patients with Hepatocellular Carcinoma: A Single Center Experience


Summary


Researchers from Mt. Sinai recently presented their findings on a retrospective analysis of patients with well compensated hepatocellular cancer(HCC) who underwent preoperative portal vein embolization (PVE) that would allow surgical treatment (≤ 40% of functional liver remnant (FLR)) with curative intention was performed. 82 patients underwent PVE, 72(87.8%) were deemed surgical candidates and 69(84.1%) underwent surgical resection.

Embolization was performed using N-butyl cyanoacrylate glue mixed with lipoidol or sodium tetradecyl sulfate foam. Tumor progression, total liver volume (TLV), FLR, hypertrophy rate and the kinetic growth rate were evaluated 4-8 weeks after PVE. Resection was performed in 84% of patients. Post resection follow up protocol included serial imaging performed every 3 months for the first 2 years and every 6 months thereafter.

Rate of major adverse events were 11% which did not depend on the embolic material used. Median increase in the FLR, hypertrophy rate and kinetic growth rate were 14.6 and 10.5%, 9.7% respectively. Radiological progression of HCC occurred in 34.1% after PVE. Post-operative morbidity was 22.2% and mortality was 4.2%. Recurrence after surgical resection was 30.4% with a mean time to recurrence of 41.9 months. The mean survival after surgical resection was 42.8 months. No significant difference in the recurrence rate, time to recurrence and survival rates was observed between patients without and with tumor progression after PVE.



Fig 1. Comparison of predicted FLR before (upper image) and after (lower image) PVE.

Commentary


Surgical resection is the procedure of choice for patient with Child A Cirrhosis who are not candidates for transplantation. The authors showed that in well selected patients PVE is a safe technique to improve the outcomes after surgical resection. Tumor progression while awaiting surgical resection can be as high as 34% and use of adjunct loco regional treatments while awaiting resection is a great option. Interestingly in this study, tumor progression after PVE did not have any influence in the recurrence rates, time to recurrence or survival after resection. Post-operative morbidity and mortality remains a concern for these patients. PVE should be considered for patients with HCC with good liver functions after carefully weighing the risks and benefits.

Click here for abstract

Marti J, Giacca M, Alshebeeb K, et al. Analysis of Preoperative Portal Vein Embolization Outcomes in Patients with Hepatocellular Carcinoma: A Single-Center Experience. J Vasc Interv Radiol 2018; 29:920-6.

Post Author:
Anil K Pillai, MD
Associate Professor and Section Chief
University of Texas Health Science Center
@AnkupiMD