A multifunctional nanoplatform for improving microwave hyperthermia by a combination therapy of vessel disruptive agent and immune modulator.

Microwave (MW) hyperthermia is one of the safest and most efficient minimally invasive tumor treatment methods, it is restricted by the bottlenecks of the heat sink effect and ineffective immune activation. Herein, a multifunctional nano platform with the load of nano immune modulator bimetallic metal-organic framework (BM), tumor vessel destructive agent and prodrug for gas production is developed for improving MW hyperthermia. Specifically, the combretastatin A4 phosphate (CA4P) was a vessel destructive agent to reduce MW heat loss by destructing the tumor blood vessel. Moreover, the as designed BM can scavenge the endogenic reactive oxygen species, which is conducive to hydrogen sulfide gas (H2S) that produced by bismuth sulfide (Bi2S3) to activate immune cells. Our in vivo experimental results demonstrate the destruction of tumor blood vessels coupled with the activated immune system results in the remarkable antitumor effect. This study provides an efficient strategy to improve MW hyperthermia by a combination of vasculature-targeting therapy with systemic immunity.

In Vivo Microwave Ablation of Normal Swine Lung at High-power, Short-duration Settings.

To evaluate the volume and heat-sink effects of microwave ablation (MWA) in the ablation zone of the normal swine lung. MWA at 100 W was performed for 1, 2, and 3 min in 7, 5, and 5 lung zones, respectively. We assessed the histopathology in the ablation zones and other outcome measures: namely, length of the longest long and short axes, sphericity, ellipsoid area, and ellipsoid volume. The mean long- and short-axis diameters were 22.0 and 14.1 mm in the 1-min ablation zone, 27.6 and 20.2 mm in the 2-min ablation zone; and 29.2 and 21.2 mm in the 3-min ablation zone, respectively. All measures, except sphericity, were significantly less with 1-min ablation than with either 2- or 3-min ablation. There were no significant differences between the 2- and 3-min ablation zones, but all measures except sphericity were larger with 3-min ablation. Although there were no blood vessels that resulted in a heat-sink effect within the ablation zones, the presence of bronchi nearby in 5 lung ablation zones resulted in reduced ablation size. In high-power, short-duration MWA, the lung ablation volume was affected by ablation time. Some ablations showed that a heat-sink effect by a neighboring bronchus might occur.

Suppression of Local Tumor Progression in Perivascular Hepatocellular Carcinoma by Combination Therapy with Radiofrequency Ablation and Percutaneous Ethanol Injection: A Propensity Score Matching Analysis.

BACKGROUND AND AIMS: Radiofrequency ablation (RFA) has replaced percutaneous ethanol injection (PEI) as the treatment of choice for hepatocellular carcinoma (HCC); however, control of local tumor progression (LTP) remains a challenge in perivascular HCC. The aim of this study was to determine whether PEI added to RFA can reduce the LTP rate in perivascular HCC patients. METHODS: We retrospectively analyzed 167 patients, with 197 newly diagnosed HCC nodules with peritumoral vessels, who underwent either RFA plus PEI or RFA monotherapy as the first-line treatment between June 2001 and April 2015. Ethanol was injected inside the tumor close to the peritumoral vessels in the combination therapy group. Patients were matched 1:1 according to their propensity scores to reduce selection bias; cumulative LTP was then analyzed using log-rank tests and Cox proportional hazard regression analyses. RESULTS: The two matched groups comprised 62 tumors each. The overall median follow-up period was 34 months (range, 1-140 months). In the RFA plus PEI group, the cumulative LTP rates were 5.7%, 15.5%, and 20.4% at 1, 3, and 5 years, respectively; in the RFA monotherapy group, the rates were 13.2%, 32.0%, and 40.2%, respectively. The rates were significantly lower in the RFA plus PEI group (p = 0.032). Cox proportional hazard regression analysis showed that PEI combination treatment was significantly associated with a reduced risk of local HCC recurrence (hazard ratio, 0.44; 95% confidence interval, 0.19-0.93; p = 0.031). DISCUSSION/CONCLUSION: The risk of LTP after RFA for perivascular HCC can be significantly reduced by injecting ethanol close to the peritumoral vessels.

A review of conventional and newer generation microwave ablation systems for hepatocellular carcinoma.

Although microwave ablation (MWA) exhibits a high thermal efficiency, the major limitation of conventional MWA systems is the lack of predictability of the ablation zone size and shape. Therefore, a specific newer generation MWA system, The Emprint™ Ablation System with Thermosphere™ Technology, was designed to create predictable large spherical zones of ablation that are not impacted by varying tissue environments. The time required for ablation with MWA systems is short, and the shape of the necrosis is elliptical with the older systems and spherical with the new system. In addition, because MWA has no heat-sink effect, it can be used to ablate tumors adjacent to major vessels. Although these factors yield a large ablation volume and result in good local control, excessive ablation of liver tissue and unexpected ablation of surrounding organs are possible. Therefore, MWA should be carefully performed. This review highlights the efficacy and complications of MWA performed with conventional systems and the newer generation system in patients with hepatocellular carcinoma (HCC). MWA with the newer generation system seems to be a promising treatment option for large HCCs and secondary hepatic malignancies, with several advantages over other available ablation techniques, including conventional MWA. However, further randomized controlled trials are necessary to fully clarify the benefits and pitfalls of this new system.

Application of oxytocin in ultrasound-guided percutaneous microwave ablation for treatment of hypervascular uterine fibroids: a preliminary report.

Objective: This study evaluated the effect of oxytocin administration prior to microwave ablation (MWA) of hypervascular uterine fibroids. Methods: Thirty-two patients with 38 hypervascular uterine fibroids (Adler blood flow grade 3) were equally apportioned to receive intravenous oxytocin infusion (0.32 U/min) 20 min before ultrasound-guided percutaneous MWA, or no oxytocin (control). Changes in Adler blood supply grade and myoma volume were observed via color Doppler ultrasonography (CDU). All patients underwent quantitative ablation with single or double needle and microwave power 50 W (180 s). Treatment continued for those who did not reach the therapeutic goal. The myoma necrotic volume was evaluated by contrast-enhanced ultrasound. Ablation rate was the percent of MRI nonenhanced myoma volume after treatment, relative to myoma volume before treatment, 2 days after surgery. Results: Twenty minutes after oxytocin administration, CDU showed significant decrease of blood vessels in myomas, and Adler blood supply decreased from grade 3 to grade 1 or grade 0 in 10 and 9 myomas, respectively. Myoma volumes were reduced by 2.12 ± 0.24%. Necrotic volumes in the oxytocin (control) groups were 36.96 ± 2.78 cm3 (22.68 ± 3.38 cm3) and ablation rates were 95.4 ± 2.7% (85.7 ± 3.3%; t = 12.68, 8.866, p = 0.001, both). No serious complication was noted. Conclusion: Intravenous oxytocin administered before percutaneous MWA of hypervascular uterine fibroids can effectively block the blood supply vessels of the myoma, reduce the heat sink effect, and thereby increase the ablation volume and improve the local therapeutic effect.

Hydrodissection of the Retrohepatic Space: A Technique to Physically Separate a Liver Tumour from the Inferior Vena Cava and the Ostia of the Hepatic Veins.

OBJECTIVE: To report a technique of percutaneous retrohepatic hydrodissection, highlighting its potential to physically separate liver tumours from the inferior vena cava (IVC) and the ostia of the hepatic veins (HV). MATERIALS AND METHODS: Between December 2017 and April 2018, hydrodissection of the retrohepatic IVC was performed in 5 patients (5 females; mean age 64.5 years) undergoing percutaneous ablation of 5 liver metastases (mean size: 3.6 cm) located adjacent to the IVC. Number of hydrodissection needles, volume of hydrodissection, separation of tumour/liver parenchyma from IVC/HV post-hydrodissection; technical success of ablation; and complications were tabulated. RESULTS: Two to three 22G spinal needles were required per case for adequate dissection. Mean volume to obtain sufficient hydrodissection was 410 ml on average. Physical separation of the IVC and tumour/hepatic parenchyma was successful in all cases, by 9 mm on average (range 5-12 mm). It also leaded to physical separation of the ostia of the right and middle HV in all cases. There was no early or delayed complication, notably no venous thrombosis in the post-operative period. All lesions but one were completely ablated after one session at 3-month follow-up. The patient with residual tumour was successfully retreated. CONCLUSION: Retrohepatic hydrodissection is a feasible technique to separate a tumour from the IVC and/or ostia of the HV. This could potentially limit the heat-sink effect/reduce the risk of thrombosis. Larger follow-up studies are required to assess efficacy on a long-term basis.

Comparison of microwave thermosphere ablation and conventional microwave ablation in ex vivo bovine livers / 中华超声影像学杂志

Objective To compare the effectiveness of microwave thermosphere ablation( M T A ) and traditional microwave ablation( M WA ) in ex v ivo bovine livers ,and to compare the degree of the heat sink effect in them .Methods T he non‐vessel model and vessel model were established using fresh bovine livers . In non‐vessel model ( n ＝ 48 ) ,the same power‐time settings were used in both M T A group and MWA group ,w hich were 80 W 12 min ,90 W 10 min and 100 W 10 min ,respectively . Long‐axis diameter ( Dl) , short‐axis diameter( Ds1 ,Ds2) ,roundness index ( R) and the time of temperature rising to 60℃ at place of 10 mm from the needle were measured .In vessel model( n ＝144) ,different vessel diameters( 3 mm ,5 mm ,10 mm) and flow rates ( 15 cm/s ,20 cm/s ,30 cm/s) were setted . The maximum radius( Rmax) ,total area of ablation zone( Sz ) ,and the area difference ( Sdiff ) were analyzed ,the temperatures adjacent to the vessel were monitored simultaneously . Results In non‐vessel model ,with the same power and time settings ,the Dl of M T A group was significantly smaller than MWA group ( P ＜ 0 .01 ) , however , there was no significant difference of Ds1 and Ds2 between the two groups( P ＞0 .05) . And M T A group created more spherical ablation zones ,since the R of M T A group were more close to 1 ( P ＜0 .01) . In M T A group ,the time of temperature rising to 60 ℃ at place of 10 mm from the needle was slower than MWA group ( P ＜0 .01) . In vessel model ,the Sdiff of M T A group were hardly affected by the vessel diameters and flow rates ( P ＞0 .05) ,and there was also no statistical significance among different flow rates( P ＞0 .05 ) in M WA group ,but the Sdiff of M WA group was significantly affected by the vessel diameters( P ＜0 .01) . And the Sdiff of M T A group was significantly smaller than M WA group when the vessel diameter was 10 mm ( P ＜0 .05) ,while there was no statistical significance between the two groups w hen the vessel diameter was 3 mm or 5 mm( P ＞0 .05) . Conclusions Compared to M WA ,M T A can produce sizable ,regular and more spherical ablation lesions with the same power and time ,meanwhile ,it is less affected by the heat sink effect .

High power microwave ablation of normal swine lung: impact of duration of energy delivery on adverse event and heat sink effects.

PURPOSE: The purpose of this study is to assess the impact of duration of energy delivery on adverse events (AEs) and heat sink effects during high power microwave ablation (MWA) of normal swine lung. MATERIALS AND METHODS: High power (100 W) MWA was performed with short (2 min, 18 ablations) or long (10 min, nine ablations) duration of energy delivery in unilateral lung of swine (n = 10). CT imaging was done prior to sacrifice at 2 or 28 d post-treatment, with additional imaging at 7 and 14 d for the latter cohort. Ablation zones were assessed with CT imaging and histopathology analysis. Differences in AEs and ablation characteristics between groups were compared with Fisher's exact test and Student's t-test, respectively. RESULTS: There were no significant differences in formation of air-filled needle tract, cavitation, and pneumonia (p > 0.5) between the treatment groups. Intra-procedural pneumothorax requiring chest tube placement occurred in three animals. Substantial (>20%, p = 0.01) intra-procedural ablation zone distortion was observed in both groups. The presence of large airways or blood vessels did not result in heat sink effect within the ablation zones and was not indicative of reduced ablation size. Increased energy delivery yielded larger (8.9 ± 3.1 cm3 vs. 3.4 ± 1.7 cm3, p < 0.001) spherical ablations (sphericity: 0.70 ± 0.10 vs. 0.56 ± 0.13, p = 0.01). CONCLUSIONS: High power MWA of normal lung with longer duration of energy delivery can create larger spherical ablations, without significant differences in post-procedure AEs when compared with shorter energy delivery time.

Understanding the nuances of microwave ablation for more accurate post-treatment assessment.

Microwave ablation (MWA) is a relatively new thermal modality for minimally invasive procedures compared with radiofrequency ablation. Although MWA and radiofrequency ablation are thermal modalities, their underlying physics and principles greatly differ. Consequently, it is imperative that clinicians be aware of how these differences impact realized ablation volumes to consistently ensure technical success and better patient outcomes. This paper will review the nuances specific to MWA technology (i.e., tissue properties, perfusion/heat sink effect, ablation assessment, imaging accuracy and tissue contraction) that are often overlooked based on familiarity with conventional thermal modalities to guide more accurate assessment of post-treatment MWA volumes.

The in vivo performance of a novel thermal accelerant agent used for augmentation of microwave energy delivery within biologic tissues during image-guided thermal ablation: a porcine study.

OBJECTIVES: To investigate the effects of a novel caesium-based thermal accelerant (TA) agent on ablation zone volumes following in vivo microwave ablation of porcine liver and skeletal muscle, and to correlate the effects of TA with target organ perfusion. MATERIALS AND METHODS: This prospective study was performed following institutional animal care and use committee approval. Microwave ablation was performed in liver and resting skeletal muscle in eight Sus scrofa domesticus swine following administration of TA at concentrations of 0 mg/mL (control), 100 mg/mL and 250 mg/mL. Treated tissues were explanted and stained with triphenyltetrazolium chloride (TTC) for quantification of ablation zone volumes, which were compared between TA and control conditions. Hematoxylin and eosin (H&E) staining was also performed for histologic analysis. General mixed modelling with a log-normal distribution was used for all quantitative comparisons (p = 0.05). RESULTS: A total of 28 ablations were performed in the liver and 18 in the skeletal muscle. The use of TA significantly increased ablation zone volumes in a dose-dependent manner in both the porcine muscle and liver (p < 0.01). Both the absolute mean ablation zone volume and percentage increase in ablation zone volume were greater in the resting skeletal muscle than in the liver. In one swine, a qualitative mitigation of heat sink effects was observed by TTC and H&E staining. Non-lethal polymorphic ventricular tachycardia was identified in one swine, treated with intravenous amiodarone. CONCLUSIONS: The use of a novel TA agent significantly increased mean ablation zone volumes following microwave ablation using a porcine model. The relationship between TA administration and ablation size was dose-dependent and inversely proportional to the degree of target organ perfusion, and a qualitative reduction in heat-sink effects was observed.

Impact of local lipiodol deposition in liver on necrotic area after microwave ablation in miniature pigs / 中国介入影像与治疗学

Objective To explore the impact of local lipiodol deposition in liver of miniature pigs on the shape and size of the necrotic area after microwave ablation (MWA).Methods Ten healthy miniature pigs were selected and equally divided into experimental group and control group (each n=5).In experimental group,transcatheter hepatic arterial embolization with lipiodol was done before microwave ablation,while only standard microwave ablation was performed in control group.Immediate post-ablation CT images were obtained.Long-axis diameter (LAD),short-axis diameter (SAD),sphericity index (SI=SAD/LAD) and volume of ablation zone were calculated.The size and shape of the ablated areas were compared between two groups.Results The mean LAD,SAD,SI and volume of ablation zone in experimental group ([4.21 ± 0.52]cm,[2.87±0.38]cm,0.69±0.10,[18.72±6.08]cm3) were larger than those in control group ([3.71±0.42]cm,[2.19±0.42]cm,0.60±0.09,[9.44±2.29] cm3;all P＜0.05).Conclusion Local deposition of lipiodol in liver parenchyma of miniature pigs can help to produce larger and rounder necrosis in the ablation zone.

Protective and Heat Retention Effects of Thermo-sensitive Basement Membrane Extract (Matrigel) in Hepatic Radiofrequency Ablation in an Experimental Animal Study.

PURPOSE: To evaluate the protective effect of using thermo-sensitive basement membrane extract (Matrigel) for hydrodissection to minimize thermal injury to nearby structures and to evaluate its heat sink effect on the ablation zone in radiofrequency ablation (RFA) of the liver. MATERIALS AND METHODS: First, the viscosity profile and heat sink effect of Matrigel were assessed during RFA in vitro and ex vivo. Fresh pig liver tissue was used, and the temperature changes in Matrigel and in 5% dextrose in water (D5W) during RFA were recorded. Then, the size of the ablation zone in the peripheral liver after RFA was measured. Second, in an in vivo study, 45 Sprague-Dawley rats were divided into three groups of 15 rats each (Matrigel, D5W and control). In the experimental groups, artificial ascites with 10 ml of Matrigel or D5W were injected using ultrasound guidance prior to RFA. The frequency of thermal injury to the nearby organs was compared among the three groups, with assessments of several locations: near the diaphragm, the abdominal wall and the gastrointestinal (GI) tract. Finally, the biological degradation of Matrigel by ultrasound was evaluated over 60 days. RESULTS: First, Matrigel produced a greater heat retention (less heat sink) effect than D5W during ex vivo ablation (63 ± 9 vs. 26 ± 6 °C at 1 min on the surface of the liver, P < 0.001). Hepatic ablation zone volume did not differ between the two groups. Second, thermal injury to the nearby structures was found in 14 of 15 cases (93.3%) in the control group, 8 of 15 cases (53.3%) in the D5W group, and 1 of 15 cases (6.7%) in the Matrigel group. Significant differences in the thermal injury rates for nearby structures were detected among the three groups (P < 0.001). The most significant difference in the thermal injury rate was found in locations near the GI tract (P = 0.003). Finally, Matrigel that was injected in vivo was gradually degraded during the following 60 days. CONCLUSIONS: Using thermo-sensitive Matrigel as a hydrodissection material might help reduce the frequency of collateral thermal injury to nearby structures, especially in locations close to the GI tract, compared to conventional D5W. Additionally, Matrigel did not increase the heat sink effect on the ablation zone during ablation and was degraded over time in vivo.

The vascular cooling effect in hepatic multipolar radiofrequency ablation leads to incomplete ablation ex vivo.

PURPOSE: Major limitations of conventional RFA are vascular cooling effects. However, vascular cooling effects are supposed to be less pronounced in multipolar RFA. The objective of this ex vivo study was a systematic evaluation of the vascular cooling effects in multipolar RFA. MATERIALS AND METHODS: Multipolar RFA with three bipolar RFA applicators was performed ex vivo in porcine liver (applicator distance 20 mm, energy input 40 kJ). A saline-perfused glass tube ('vessel') was placed parallel to the applicators in order to simulate a natural liver vessel. Five applicator-to-vessel geometries were tested. A liquid-filled glass tube without perfusion was used as a dry run. Ablations were orthogonally cut to the applicators at a defined height. Cooling effects were analysed qualitatively and quantitatively along these cross sectional areas. RESULTS: Thirty-six ablations were performed. A cooling effect could be seen in all ablations with perfused vessels compared to the dry run. While this cooling effect did not have any influence on the ablation areas (859-1072 mm(2) versus 958 mm(2) in the dry run, p > 0.05), it had a distinctive impact on ablation shape. A vascular cooling effect could be observed in all ablations with perfusion directly around the vessel independent of the applicator position compared to the dry run (p < 0.01). CONCLUSIONS: A vascular cooling effect occurred in all multipolar RFA with simulated liver vessels ex vivo independent of the applicator-to-vessel geometry. While the cooling effect did not influence the total ablation area, it had a distinctive impact on the ablation shape.

Effect of one-off complete tumor radiofrequency ablation on liver function and postoperative complication in small hepatocellular carcinoma.

OBJECTIVE: Radiofrequency ablation (RFA) is effective in treating hepatocellular carcinoma (HCC) and less invasive than surgical resection. However, 'one-off' complete tumor ablation on liver function has not been reported. METHODS: We retrospectively reviewed 36 HCCs which met the criteria of 'one-off' complete tumor ablation: (1) tumor was completed covered by the ablated zone (confirmed by postoperative enhanced CT) with a single RFA and, (2) no sign of recurrence for at least 6 months. We categorized tumors into two groups: near vascular tumor (NVT) if the distance was less than 5 mm, and far vascular tumor (FVT) otherwise. RESULTS: Thirteen HCCs met the criteria of NVTs, and 23 HCCs met that of FVTs. The Average tumor size was 2.6 ± 0.3 cm in FVTs and 2.5 ± 0.3 cm in NVTs. Although restored to normal range by postoperative day (POD) 7, ALT, AST, total bilirubin (TB), albumin and prothrombin time showed more significant fluctuation in NVTs compared to those in FVTs on POD1 through POD5. Moreover, 53.9% (7/13) patients in NVT group and 26.1% (6/23) in FVT group developed post-RFA transient ascites (OR = 5.1, 95% CI = 1.1-24.4). Incidence of post-RFA pleural effusion were 61.5% (8/13) in NVT but only 17.4% (4/23) in FVTs (OR = 7.6, 95% CI = 1.6-35.9). CONCLUSION: 'One-off' complete tumor ablation may impair liver function and led to more postoperative complication if a tumor is within 5 mm away from a large blood vessel (≥ 3 mm). Particular caution should be made in preoperative assessment on the anatomic relation between tumor and large blood vessel for patients.