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The immune response to cancer is an ongoing area of interest and is the focus of newer systemic agents. Liver-directed therapy has been the standard treatment for primary and metastatic disease limited to the liver. It is increasingly being recognized that these therapies may influence a broader systemic response and immune activation. The clinical and translational data supporting this phenomenon are reviewed herein. The findings and potential impact of the immune response to liver-directed therapies are summarized in this article.

PURPOSE: The purpose of this study was to elicit the relationship of antiplatelet therapy (AP) in maintaining arteriovenous graft (AVG) patency after successful percutaneous pharmacomechanical thrombectomy (“declot”). MATERIALS & METHODS: This was an institutional review board-approved retrospective review of AVG declot procedures between July 2019 and August 2020. AVG characteristics, bleeding complications, anticoagulation and antiplatelet medication regimens, and thrombosis free survival were evaluated. Recurrent time-to-event analysis was performed using a Prentice-Williams-Peterson Gap time model was performed to evaluate AVG thrombosis free survival. RESULTS: A total of 109 declots were technically successful and performed in 63 individual patients. The majority of procedures were performed in upper arm grafts (71%, n=45). Dual antiplatelet (DAPT) was prescribed after 52 declots (48%), single antiplatelet was prescribed after 36 declots (33%), and anticoagulation was prescribed after 31 declots (28%). Median thrombosis free survival was 37 days (range 1–412 days) in the no antiplatelet group, 84 days (range 1–427 days) in the single antiplatelet group, and 93 days (range 3–407 days) in the DAPT group. Anti-platelet medications trended towards protective of AVG thrombosis in multivariate analysis (hazard ratio 0.84, 95% confidence interval 0.60–1.19); however, this did not reach statistical significance (P=0.33). A total of 4 major and 5 minor bleeding events occurred. CONCLUSION: The results of this study support further evaluation of AP therapy in preventing secondary rethrombosis of dialysis AVG.

We sought to evaluate differences in outcomes between double versus triple transarterial chemoembolization (TACE). TACEs over a 1-year period were retrospectively reviewed and divided into two groups: double and triple. Imaging response and complications were made on a per-procedure basis. Student's t-test was used to calculate differences in continuous variables, and chi-square test was used to calculate differences in categorical values.Overall tumor response was similar between the two groups, and there were no significant differences in complications between groups. Outcomes are similar between double and triple conventional TACE, suggesting that adding a third drug may only contribute to cost.

BACKGROUND: US contrast agents are gas-filled microbubbles (MBs) that can be locally destroyed by using external US. Among other bioeffects, US-triggered MB destruction, also known as UTMD, has been shown to sensitize solid tumors to radiation in preclinical models through localized insult to the vascular endothelial cells. PURPOSE: To evaluate the safety and preliminary efficacy of combining US-triggered MB destruction and transarterial radioembolization (TARE) in participants with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: In this pilot clinical trial, participants with HCC scheduled for sublobar TARE were randomized to undergo either TARE or TARE with US-triggered MB destruction 1–4 hours and approximately 1 and 2 weeks after TARE. Enrollment took place between July 2017 and February 2020. Safety of US-triggered MB destruction was evaluated by physiologic monitoring, changes in liver function tests, adverse events, and radiopharmaceutical distribution. Treatment efficacy was evaluated by using modified Response Evaluation Criteria in Solid Tumors (mRECIST) on cross-sectional images, time to required next treatment, transplant rates, and overall survival. Differences across mRECIST reads were compared by using a Mann-Whitney U test, and the difference in prevalence of tumor response was evaluated by Fisher exact test, whereas differences in time to required next treatment and overall survival curves were compared by using a log-rank (Mantel-Cox) test. RESULTS: Safety results from 28 participants (mean age, 70 years ± 10 [standard deviation]; 17 men) demonstrated no significant changes in temperature (P = .31), heart rate (P = .92), diastolic pressure (P = .31), or systolic pressure (P = .06) before and after US-triggered MB destruction. No changes in liver function tests between treatment arms were observed 1 month after TARE (P > .15). Preliminary efficacy results showed a greater prevalence of tumor response (14 of 15 [93%; 95% CI: 68, 100] vs five of 10 [50%; 95% CI: 19, 81]; P = .02) in participants who underwent both US-triggered MB destruction and TARE (P = .02). CONCLUSION: The combination of US-triggered microbubble destruction and transarterial radioembolization is feasible with an excellent safety profile in this patient population and appears to result in improved hepatocellular carcinoma treatment response. © RSNA, 2020

The purpose of this study was to evaluate the effect of spinal bone radiofrequency ablation (RFA) with and without controlled saline infusion. RFA with and without controlled saline infusion was performed in the vertebral bodies of 2 swine with real-time temperature and impedance recordings. Histology and MRI were reviewed to evaluate ablation zone size, breach of spinal canal, and damage to spinal cord and nerves. There was no difference in maximum and mean temperatures between controlled saline and non-infusion groups. Impedance and power output were not significantly different between groups. MRI and histopathology demonstrated ablation zones confined within vertebral bodies. Ablation zone size correlated on MRI and histopathology by group. No ablation effect, breach of posterior cortex, spinal cord injury, nor nerve/ganglion injury were seen at any level on MRI or histology. Controlled saline infusion does not appear to impact bone RFA.

In recent years, there has been increased utilization of microwave ablation (MWA) in the treatment of soft tissue tumors. MWA has several theoretical advantages over radiofrequency ablation (RFA) by achieving a more rapid and sustained heating of tissues, increased efficacy in tissues with poor thermal conductivity, and less susceptibility to heat sink effect. While its greater power output has led to appropriate caution when applying this energy to soft tissue tumors, many commonly held beliefs regarding contraindications to MWA are unsupported by data and have been passed along based on experience with RFA. The goal of this article is to review the use of MWA in challenging clinical situations along with the existing evidence for its use.

This report describes intranodal lymphatic embolization for treatment of groin lymphatic leaks following surgery or percutaneous vascular interventions. In 10 consecutive patients with groin lymphatic leak between 2015 and 2017, lymphangiography with embolization was performed by intranodal injection with dilute N-butyl cyanoacrylate (NBCA). Mean volume of dilute NBCA (1:3 with ethiodized oil) injected was 1 mL. Clinical success rate was 80%. Median time to resolution was 7 days. Intranodal lymphatic embolization for treatment of groin lymphatic leaks is a safe and effective treatment alternative to surgery resulting in a rapid time to resolution.

Purpose To determine the feasibility of creating a clinically relevant hepatic ablation (ie, an ablation zone capable of treating a 2-cm liver tumor) by using robotically assisted sonic therapy (RAST), a noninvasive and nonthermal focused ultrasound therapy based on histotripsy. Materials and Methods This study was approved by the institutional animal use and care committee. Ten female pigs were treated with RAST in a single session with a prescribed 3-cm spherical treatment region and immediately underwent abdominal magnetic resonance (MR) imaging. Three pigs (acute group) were sacrificed immediately following MR imaging. Seven pigs (chronic group) were survived for approximately 4 weeks and were reimaged with MR imaging immediately before sacrifice. Animals underwent necropsy and harvesting of the liver for histologic evaluation of the ablation zone. RAST ablations were performed with a 700-kHz therapy transducer. Student t tests were performed to compare prescribed versus achieved ablation diameter, difference of sphericity from 1, and change in ablation zone volume from acute to chronic imaging. Results Ablation zones had a sphericity index of 0.99 ± 0.01 (standard deviation) (P < .001 vs sphericity index of 1). Anteroposterior and transverse dimensions were not significantly different from prescribed (3.4 ± 0.7; P = .08 and 3.2 ± 0.8; P = .29, respectively). The craniocaudal dimension was significantly larger than prescribed (3.8 ± 1.1; P = .04), likely because of respiratory motion. The central ablation zone demonstrated complete cell destruction and a zone of partial necrosis. A fibrous capsule surrounded the ablation zone by 4 weeks. On 4-week follow-up images, ablation zone volumes decreased by 64% (P < .001). Conclusion RAST is capable of producing clinically relevant ablation zones in a noninvasive manner in a porcine model. © RSNA, 2018.

Microwave (MW) ablation was used to treat 12 hepatocellular adenomas in six patients (five women and one man; mean age, 39.6 y). Mean treated tumor size was 2.7 cm ± 2.0. Tumor response was evaluated with serial cross-sectional imaging for a mean follow-up of 12.6 months ± 7.1. Primary treatment effectiveness and local tumor control were 100%. There were no instances of hemorrhage, malignant transformation, new hepatic tumors, or extrahepatic metastases. This early experience of treatment of hepatic adenomas by MW ablation demonstrates it to be a safe and feasible treatment modality at short-term follow-up. Continued investigation, including comparison with other treatment modalities, is warranted.

PURPOSE: Robotically assisted sonic therapy (RAST) is a nonthermal, noninvasive ablation method based on histotripsy. Prior animal studies have demonstrated the ability to create hepatic ablation zones at the focal point of an ultrasound therapy transducer; however, these treatments resulted in thermal damage to the body wall within the path of ultrasound energy delivery. The purpose of this study was to evaluate the efficacy and safety of a pulse sequence intended to mitigate prefocal body wall injury. MATERIALS AND METHODS: Healthy swine (n = 6) underwent hepatic RAST (VortxRx software version 1.0.1.3, HistoSonics, Ann Arbor MI) in the right hepatic lobe. A 3.0 cm spherical ablation zone was prescribed for each. Following treatment, animals underwent MRI which was utilized for ablation zone measurement, evaluation of prefocal injury, and assessment of complications. Each animal was euthanized, underwent necropsy, and the tissue was processed for histopathologic analysis of the ablation zone and any other sites concerning for injury. RESULTS: No prefocal injury was identified by MRI or necropsy in the body wall or tissues overlying the liver. Ablation zones demonstrated uniform cell destruction, were nearly spherical (sphericity index = 0.988), and corresponded closely to the prescribed size (3.0 9 3.1 9 3.4 cm, p = 0.70, 0.36, and 0.01, respectively). Ablation zones were associated with portal vein (n = 3, one occlusive) and hepatic vein thrombosis (n = 4, one occlusive); however, bile ducts remained patent within ablation zones (n = 2). CONCLUSIONS: Hepatic RAST performed with a modified ultrasound pulse sequence in a porcine model can mitigate prefocal body wall injuries while maintaining treatment efficacy. Further study of hepatic RAST appears warranted, particularly in tumor models.

To compare transarterial chemoembolization (TACE) monotherapy to combination TACE and microwave ablation (MWA) for local control of 3- to 5-cm hepatocellular carcinoma (HCC). Patients with HCC between 3 and 5 cm treated with TACE monotherapy or combination TACE + MWA at a single institution between 2007 and 2016 were retrospectively reviewed. Twenty-four HCCs (median diameter 3.8 cm) in 16 patients (13 males; median age 64 years) were treated using TACE monotherapy. Combination TACE + MWA was used to treat 23 HCCs (median diameter 4.2 cm) in 22 patients (18 males; median age 61 years). Microwave ablation was performed at a target time of two weeks following TACE. Individual tumors were followed by serial contrast-enhanced CT or MR. Response to treatment was evaluated on a tumor-by-tumor basis using mRECIST criteria with the primary outcome being local tumor progression (LTP). Data were analyzed using Fisher’s exact test for categorical variables and Wilcoxon rank sum test for continuous variables. Time to LTP was estimated with the Kaplan–Meier method. Relative to TACE monotherapy, TACE + MWA provided a trend toward both a lower rate of LTP (34.8% vs. 62.5%, p = 0.11) and a higher complete response rate (65.2% vs. 37.5%; p = 0.12). Time to LTP (22.3 months vs. 4.2 months; p = 0.001) was significantly longer in the TACE + MWA group compared to TACE monotherapy. Combination therapy with TACE and microwave ablation improves local control and increases time to LTP for 3–5 cm HCC.

OBJECTIVE. The purpose of this study was to evaluate the incidence of clinically significant diaphragmatic injuries and local tumor progression after microwave ablation of hepatic tumors abutting the diaphragm. MATERIALS AND METHODS. This retrospective study included 55 peripheral hepatic tumors abutting the diaphragm treated by microwave ablation versus a control group of 15 centrally located tumors. Treated tumors were further subdivided according to the use of artificial ascites (fluid vs no fluid) and whether instilled fluid achieved displacement of the liver surface away from the diaphragm (displaced vs nondisplaced). Measurements of tumor size, distance to the diaphragm, ablation zone size, displacement distance, length of the ablation zone along the liver capsule, diaphragm thickness, diaphragmatic hernia, and local tumor progression were made on pre- and postablation CT and MRI. The electronic medical record was reviewed for patient self-reported pain scores and other symptoms. Data were analyzed by use of the Kruskal-Wallis and Fisher exact tests. RESULTS. There were no cases of diaphragmatic hernia in peripheral or central tumors. Postablation diaphragm thickness was higher in peripheral hepatic tumors than in control tumors. Peripheral tumors had an overall higher incidence of postprocedure shoulder pain (18% vs 0%) and local tumor progression (5.5% vs 0%) compared with control tumors, but these differences did not achieve statistical significance (p = 0.2 and p = 1, respectively). CONCLUSION. Our study shows that microwave ablation of peridiaphragmatic hepatic tumors is safe, without incidence of diaphragmatic hernia, and can be performed with a low rate of local tumor progression.

To determine the size of pulmonary artery (PA) at risk for occlusion during percutaneous microwave ablation and to assess the effect of vessel diameter, number, and patency, on ablation zone volume. Computed tomography (CT) fluoroscopy-guided percutaneous microwave ablations were performed in 8 pigs under general anesthesia. All ablations were performed at 65 W for 5 min with a single 17-gauge antenna positioned in the central third of the lungs. A CT pulmonary angiogram was performed immediately after the ablations. The maximum diameter, number and patency of PA branches within each ablation zone were recorded. Ablation volumes were measured at gross dissection and with CT. Student’s t test was used to compare ablation zone volumes among groups. Twenty-one pulmonary ablations were performed. Six of the ablation zones (29%) contained at least 1 occluded PA branch. The mean diameter of the occluded PA branches in the ablation zones (2.4 mm; range, 2.0–2.8 mm) was significantly smaller than non-occluded PA branches (3.7 mm; range: 2.1–6.9 mm; p = 0.009). No PA branches ≥3 mm in size were occluded. There was no significant difference in volume of gross ablation zones that contained occluded versus non-occluded PAs (p = 0.42), one versus multiple PAs (p = 0.71), or PAs

Purpose To demonstrate the feasibility of Robotically Assisted Sonic Therapy (RAST)—a noninvasive and nonthermal focused ultrasound therapy based on histotripsy—for renal ablation in a live porcine model. Materials and Methods RAST ablations (n = 11) were performed in 7 female swine: 3 evaluated at 1 week (acute) and 4 evaluated at 4 weeks (chronic). Treatment groups were acute bilateral (3 swine, 6 ablations with immediate computed tomography [CT] and sacrifice); chronic single kidney (3 swine, 3 ablations; CT at day 0, week 1, and week 4 after treatment, followed by sacrifice); and chronic bilateral (1 swine, 2 ablations). Treatments were performed using a prototype system (VortxRx; HistoSonics, Inc) and targeted a 2.5-cm-diameter sphere in the lower pole of each kidney, intentionally including the central collecting system. Results Mean treatment time was 26.4 minutes. Ablations had a mean diameter of 2.4 ± 0.3 cm, volume of 8.5 ± 2.4 cm3, and sphericity index of 1.00. Median ablation volume decreased by 96.1% over 4 weeks. Histology demonstrated complete lysis with residual blood products inside the ablation zone. Temporary collecting system obstruction by thrombus was observed in 4/11 kidneys (2 acute and 2 chronic) and resolved by 1 week. There were no urinary leaks, main vessel thromboses, or adjacent organ injuries on imaging or necropsy. Conclusions In this normal porcine model, renal RAST demonstrated complete histologic destruction of the target renal tissue while sparing the urothelium.

Purpose To evaluate safety and efficacy of percutaneous hepatic microwave (MW) ablation performed near the heart. Materials and Methods This study reviewed 118 consecutive peripheral (ablation zone margins within 5 mm of liver capsule) percutaneous MW hepatic ablations performed between June 2010 and August 2015. Ablation zones of 27 tumors (22.8%) extended to ≤ 5 mm from myocardium, and these ablations comprised the study group; the remaining ablations formed the control group. The study cohort included 14 men and 10 women (mean age, 59 y) with 16 hepatocellular carcinomas, 9 metastases, and 2 hemangiomas. Periprocedural imaging was used to evaluate tumor size and distance from the heart, ablation zone size, and complications. Mean tumor size and distance to myocardium were 2.6 cm ± 1.7 and 1.1 cm ± 1.1, respectively. The electronic medical record was used to retrospectively assess local tumor progression (LTP) and electrocardiogram and hemodynamic alterations during and after ablation. Statistical analysis was performed with Fisher exact test and t test. Results Median follow-up was 13.6 months (range, 1.2–38.7 months). No arrhythmias occurred during or after ablation in the follow-up period (0/27). There was no difference between groups in frequency of alterations in periprocedural blood pressure (25.9% vs 29.6%, p=0.81) or heart rate (18.5% vs 24.2%, P = .61) or rate of LTP (12.0% vs 10.8%, P = 1.0). Conclusions Percutaneous MW ablation near the heart may be safe and effective, without increased risk of cardiac complications and with similar rates of LTP, compared with a control group of peripheral liver ablations.

Objective— We tested the hypothesis of a role for the calcium-dependent protease calpain in the endothelial dysfunction induced by hyperglycemic activation of protein kinase C (PKC). Methods and Results— Chronic hyperglycemia with insulin deficiency (type 1 diabetes) was induced in rats by streptozotocin. Total PKC and calpain activities, along with activity and expression level of the 2 endothelial-expressed calpains isoforms, μ- and m-calpain, were measured in vascular tissue homogenates by enzymatic assays and Western blot analysis, respectively. Intravital microscopy was used to measure and correlate leukocyte-endothelium interactions with calpain activity in the microcirculation. Expression levels and endothelial localization of the inflammatory adhesion molecule intercellular adhesion molecule-1 were studied by Western blot analysis and immunofluorescence, respectively. The mechanistic role of hyperglycemia alone in the process of PKC-induced calpain activation and actions was also investigated. We found that in the type 1 diabetic vasculature, PKC selectively upregulates the activity of the μ-calpain isoform. Mechanistic studies confirmed a role for hyperglycemia and PKCβ in this process. The functional implications of PKC-induced calpain activation were upregulation of endothelial expressed intercellular adhesion molecule-1 and leukocyte-endothelium interactions. Conclusion— Our results uncover the role of μ-calpain in the endothelial dysfunction of PKC. Calpain may represent a novel molecular target for the treatment of PKC-associated diabetic vascular disease.

Objectives Direct puncture of subcapsular hepatocellular carcinoma (HCC) for tumor ablation has been considered high risk due to a perceived increased incidence of hemorrhage or tumor seeding. The purpose of this retrospective multicenter study was to identify the rate of tumor seeding, hemorrhage and local tumor progression (LTP) associated with direct puncture radiofrequency (RF) and microwave (MW) ablation of subcapsular HCC. Methods A multicenter, retrospective review of direct-puncture RF and MW performed on subcapsular HCC was conducted. Complications and local tumor progression were documented. Data was analyzed using Kaplan–Meier and log-rank tests. Results The study group consisted of 60 cirrhotic patients (M/F = 43/17; mean age 69.6 years) with 67 subcapsular HCC (mean diameter 2.3 cm ± 1.0 cm) that were directly punctured for RF (n = 40) or MW (n = 27) under ultrasound (US) guidance. The mean follow-up period was 30.8 months. There were no hemorrhagic complications. The overall LTP rate was 13.4%. There was one case of tumor tract seeding in a patient who had undergone a percutaneous biopsy two weeks prior to RF. Conclusions Thermal ablation of HCC by direct puncture appears safe and effective. There were no cases of intraperitoneal hemorrhage, and tumor seeding was seen in a single case in which a preceding percutaneous biopsy had been performed.

Image-guided percutaneous ablation techniques are increasingly being used for the treatment of malignant tumors of the liver and kidney. Contrast enhanced ultrasound (CEUS) is a real-time dynamic imaging technique that plays an important role in the pre-, intra-, and post-procedural management of these patients. This review will focus on the role of CEUS in the evaluation of patients undergoing treatment with percutaneous ablation for hepatic or renal tumors.