Dual-Applicator MR Imaging-Guided Microwave Ablation with Real-Time MR Thermometry: Phantom and Porcine Tissue Model Experiments.

PURPOSE: To investigate the effect of simultaneous use of dual applicators on the image quality of real-time magnetic resonance (MR) thermometry and to characterize the dual-applicator treatment zone pattern during MR imaging-guided microwave ablation (MWA). MATERIALS AND METHODS: MWA experiments were performed on a 1.5-T MR scanner with 2 commercial microwave systems (902-928 MHz). Phantom experiments were first performed to evaluate the effect of dual-applicator MWA on the image quality of MR. Then, porcine tissue model experiments were conducted with real-time MR thermometry using either a single applicator or dual applicators inserted 2.6, 3.6, and 4.6 cm apart. Fiberoptic thermal probes were used to measure the temperature changes at the tissue surface. RESULTS: Simultaneous use of dual applicators resulted in a decrease in the relative signal-to-noise ratio (SNR) in the MR thermometry images to 55% ± 2.9% when compared with that of a single applicator (86.2% ± 2.0%). Despite the lower SNR, the temperature and ablation zone maps were of adequate quality to allow visualization of the ablation zone(s). The extents of increase in the temperature at the tissue surface using dual applicators (19.7 °C ± 2.6 °C) and a single applicator (18.2 °C ± 3.3 °C) were not significantly different (P = .40). Treatment zones were significantly larger (P < .05) in dual-applicator ablations (29.4 ± 0.4, 39.9 ± 0.6, and 42.6 ± 0.9 cm2 with 2.6-, 3.6-, and 4.6-cm spacing, respectively) at the end of the ablation procedure than in the single-applicator MWA (18.6 ± 0.9 cm2). CONCLUSIONS: MR imaging-guided dual-applicator MWA produced larger ablation zones while allowing adequate real-time MR thermometry image quality for monitoring the evolution of the treatment zone.

Percutaneous MR Imaging-Guided Laser Ablation for the Treatment of Symptomatic Cervicofacial Vascular Malformations.

PURPOSE: To evaluate the safety and effectiveness of percutaneous magnetic resonance (MR) imaging-guided laser ablation for the treatment of symptomatic soft tissue vascular malformations (VMs) in the face and neck. MATERIALS AND METHODS: An institutional review board-approved retrospective review was undertaken of all consecutive patients who underwent MR imaging-guided and monitored laser ablation for treatment of symptomatic, cervicofacial soft tissue VM. Preablation and postablation MR imaging findings were independently reviewed. Preablation and postablation VM sizes were documented. Preablation T2 signal characteristics and enhancement patterns as well as postablation change in both signal and enhancement were semiquantitatively assessed. Changes in VM size were compared using a paired t test. RESULTS: Thirteen patients (women, 9; age, 14.5-69.5 years) with 13 VMs were treated for moderate-to-severe pain (n = 4), swelling/mass effect (n = 8), or predominantly cosmesis (n = 1) with 22 total ablation sessions. The baseline maximum VM diameter was 5.7 cm ± 4.2. At baseline, all VMs (100%) demonstrated variable T2-weighted signal hyperintensity and enhancement. For painful VM, the baseline pain score was 8 ± 1. Clinical follow-up was available for 10 patients. Of patients with available follow-up, 3 (100%) treated for moderate-to-severe pain and 7 (100%) treated for swelling/mass effect reported subjective complete or partial symptomatic relief. The patient treated predominantly for cosmetic reasons was lost to follow-up. Two patients (15.4%) experienced minor adverse events by the Society of Interventional Radiology standards. There were no major adverse events. CONCLUSIONS: MR imaging-guided and monitored percutaneous laser ablation is safe and effective for the treatment of symptomatic, cervicofacial VMs.

Aqueous Dispersion of Manganese-Zinc Ferrite Nanoparticles Protected by PEG as a T2 MRI Temperature Contrast Agent.

Mixed manganese-zinc ferrite nanoparticles coated with PEG were studied for their potential usefulness in MRI thermometry as temperature-sensitive contrast agents. Particles in the form of an 8.5 nm core coated with a 3.5 nm layer of PEG were fabricated using a newly developed, one-step method. The composition of Mn0.48Zn0.46Fe2.06O4 was found to have a strong thermal dependence of magnetization in the temperature range between 5 and 50 °C. Nanoparticles suspended in an agar gel mimicking animal tissue and showing non-significant impact on cell viability in the biological test were studied with NMR and MRI over the same temperature range. For the concentration of 0.017 mg/mL of Fe, the spin-spin relaxation time T2 increased from 3.1 to 8.3 ms, while longitudinal relaxation time T1 shows a moderate decrease from 149.0 to 125.1 ms. A temperature map of the phantom exposed to the radial temperature gradient obtained by heating it with an 808 nm laser was calculated from T2 weighted spin-echo differential MR images. Analysis of temperature maps yields thermal/spatial resolution of 3.2 °C at the distance of 2.9 mm. The experimental relaxation rate R2 data of water protons were compared with those obtained from calculations using a theoretical model incorporating the motion averaging regime.

MRI-guided focused ultrasound focal therapy for patients with intermediate-risk prostate cancer: a phase 2b, multicentre study.

BACKGROUND: Men with grade group 2 or 3 prostate cancer are often considered ineligible for active surveillance; some patients with grade group 2 prostate cancer who are managed with active surveillance will have early disease progression requiring radical therapy. This study aimed to investigate whether MRI-guided focused ultrasound focal therapy can safely reduce treatment burden for patients with localised grade group 2 or 3 intermediate-risk prostate cancer. METHODS: In this single-arm, multicentre, phase 2b study conducted at eight health-care centres in the USA, we recruited men aged 50 years and older with unilateral, MRI-visible, primary, intermediate-risk, previously untreated prostate adenocarcinoma (prostate-specific antigen ≤20 ng/mL, grade group 2 or 3; tumour classification ≤T2) confirmed on combined biopsy (combining MRI-targeted and systematic biopsies). MRI-guided focused ultrasound energy, sequentially titrated to temperatures sufficient for tissue ablation (about 60-70°C), was delivered to the index lesion and a planned margin of 5 mm or more of normal tissue, using real-time magnetic resonance thermometry for intraoperative monitoring. Co-primary outcomes were oncological outcomes (absence of grade group 2 and higher cancer in the treated area at 6-month and 24-month combined biopsy; when 24-month biopsy data were not available and grade group 2 or higher cancer had occurred in the treated area at 6 months, the 6-month biopsy results were included in the final analysis) and safety (adverse events up to 24 months) in all patients enrolled in the study. This study is registered with ClinicalTrials.gov, NCT01657942, and is no longer recruiting. FINDINGS: Between May 4, 2017, and Dec 21, 2018, we assessed 194 patients for eligibility and treated 101 patients with MRI-guided focused ultrasound. Median age was 63 years (IQR 58-67) and median concentration of prostate-specific antigen was 5·7 ng/mL (IQR 4·2-7·5). Most cancers were grade group 2 (79 [78%] of 101). At 24 months, 78 (88% [95% CI 79-94]) of 89 men had no evidence of grade group 2 or higher prostate cancer in the treated area. No grade 4 or grade 5 treatment-related adverse events were reported, and only one grade 3 adverse event (urinary tract infection) was reported. There were no treatment-related deaths. INTERPRETATION: 24-month biopsy outcomes show that MRI-guided focused ultrasound focal therapy is safe and effectively treats grade group 2 or 3 prostate cancer. These results support focal therapy for select patients and its use in comparative trials to determine if a tissue-preserving approach is effective in delaying or eliminating the need for radical whole-gland treatment in the long term. FUNDING: Insightec and the National Cancer Institute.

Salvage ablation for locally recurrent prostate cancer.

PURPOSE OF REVIEW: This review aims to summarize the latest evidence for the use of salvage ablation of localized prostate cancer recurrences after primary therapy radiotherapy or prostatectomy. RECENT FINDINGS: Savage ablation represents a treatment option in select patients with localized recurrences following primary therapy of prostate cancer. Following radiotherapy, salvage cryotherapy and high-intensity focused ultrasound (HIFU) demonstrate encouraging oncologic outcomes. Biochemical recurrence-free survival ranged from 71% at 2 years to 44.2% at 10 years for cryotherapy and from 51% at 5 years to 28.7% at 10 years for HIFU. Rates of adverse effects appear to be more favorable with ablation compared to salvage surgery. Focal salvage ablation may offer a further balance between oncologic control and adverse effects. Following radical prostatectomy, recent data on the use of salvage ablation of local recurrences are less robust with only a few small studies published in the last 2 years. SUMMARY: Salvage ablation is an option for localized disease recurrences following primary treatment. Its role is most established for postradiation recurrence. It can also be utilized in postprostatectomy recurrence, although published data is more limited. Future studies are needed to further explore the role of ablation in both cohorts.

Experimental Investigation of Cryoneedle Heating during MR-Guided Cryoablation in Ex Vivo Tissue Samples at 1.5-Tesla.

PURPOSE: To investigate cryoneedle heating risks during magnetic resonance (MR)-guided cryoablation and potential strategies to mitigate these risks. MATERIALS AND METHODS: Ex vivo experiments were performed on a 1.5-Tesla (T) MR scanner using an MR conditional cryoablation system on porcine tissue phantoms. Cryoneedles were placed inside the tissue phantom either with or without an angiocatheter. Typical cryoneedle geometric configurations (including gas supply line) encountered in clinical procedures with low to high expected heating risks were investigated. Up to 4 fiber optic temperature sensors were attached to the cryoneedle/angiocatheter to measure the MR-induced cryoneedle heating at different locations during MR with different estimated specific absorption rates (SARs). The impact of cryoneedle heating on cryoablation treatment was studied by comparing temperature changes during 10-min freeze-thaw cycles with and without MR. RESULTS: Rapid temperature increases of >100 °C in < 2 minutes were observed during MR with a SAR of 2.1 W/kg. The temperature changes during a typical freeze-thaw cycle were also affected by cryoneedle heating when MR was used to monitor the ice-ball evolution. The observed cryoneedle heating was affected by multiple factors; including cryoneedle geometric configurations, sequence SAR, whether an angiocatheter was used, and whether the cryoneedle was connected to the rest of the cryoablation system. CONCLUSIONS: The ex vivo experiments demonstrated that MR could induce significant cryoneedle heating risks. Furthermore, MR-induced cryoneedle heating can affect temperatures in the ice-ball evolution during the freeze-thaw cycle. Several practical strategies to reduce the cryoneedle heating have been proposed.

Percutaneous MR Imaging-Guided Laser Ablation and Cryoablation for the Treatment of Pediatric and Adult Symptomatic Peripheral Soft Tissue Vascular Anomalies.

PURPOSE: To evaluate the safety and effectiveness of percutaneous magnetic resonance (MR) imaging-guided laser ablation and cryoablation for the treatment of symptomatic soft tissue vascular anomalies (VAs) of the trunk and extremities. MATERIALS AND METHODS: An institutional review board-approved retrospective review was undertaken of all pediatric and adult patients who underwent MR imaging-guided and monitored laser ablation and/or cryoablation for the treatment of symptomatic peripheral soft tissue VA. Preablation and postablation MR imaging was independently reviewed. Pain scores on the visual analog scale (0 to 10) and self-reported subjective symptomatic improvement were assessed. Change in VA size and pain scores were compared using a paired t test. RESULTS: Thirty patients (24 females; age, 10-75 years) with 34 VAs were treated for moderate to severe pain (n = 27) or swelling/mass effect (n = 3) with 60 total ablation sessions. The baseline maximum VA diameter was 9.5 cm ± 8.6. At baseline, all VAs (100%) demonstrated variable T2-weighted signal hyperintensity and enhancement. The baseline pain score was 6.4 ± 1.6. Clinical follow-up was available for 23 patients. At a mean follow-up time of 12.2 months ± 10.1, 19 of 20 (95%) patients treated for pain and 2 of 3 (67%) patients treated for swelling/mass effect reported partial or complete symptomatic relief. There was a significant decrease in the postablation pain scores (-5.7 ± 1.0, P < .001) and maximum VA size (-2.3 cm ± 2.7, P = .004), with >50% reduction in VA T2 signal (59%) and enhancement (73%). Nine of 30 (30%) patients experienced minor complications. CONCLUSIONS: MR imaging-guided and monitored percutaneous laser ablation and cryoablation appear to be safe and effective for the treatment of symptomatic peripheral soft tissue VAs.

A Single-Institution Experience in Percutaneous Image-Guided Cryoablation of Lymph Node Metastases.

OBJECTIVE. The purpose of this study was to assess the feasibility, safety, and efficacy of percutaneous cryoablation for the treatment of lymph node metastases. MATERIALS AND METHODS. In this single-institution retrospective study 55 patients were identified who underwent CT-guided cryoablation of metastatic lymph nodes between November 2006 and September 2019. Patient demographics, disease characteristics, and procedural details were recorded. The primary endpoints were technical success and major complications. The secondary endpoints were time to local and time to distant progression. Complications were graded according to the Society of Interventional Radiology consensus guidelines. RESULTS. The study sample comprised 55 patients (42 men, 13 women; mean age 64 ± 12 years) who underwent 61 cryoablation procedures to treat 65 lymph node metastases. Targeted nodes measured 1.7 ± 1.2 cm in mean short-axis diameter. Technical success was achieved in 60 of 61 cryoablation procedures (98%). Adjunctive maneuvers performed to protect adjacent structures included hydrodissection (n = 40), ureteral stenting (n = 3), and neural monitoring (n = 3). There were two Society of Interventional Radiology major complications (3%): pneumothorax (n = 1) and bleeding (n = 1). Local tumor control was achieved in treatment of 53 of 65 (82%) nodal metastases within a median of 25 months (range, 1-121 months) of follow-up. Local progression occurred in 12 of 65 cases (18%); the median time to recurrence was 11 months. CONCLUSION. Percutaneous cryoablation of nodal metastases is feasible and safe. Further investigation is warranted to assess the long-term efficacy of this technique and to define its role in oncologic care.

Body Interventional MRI for Diagnostic and Interventional Radiologists: Current Practice and Future Prospects.

Clinical use of MRI for guidance during interventional procedures emerged shortly after the introduction of clinical diagnostic MRI in the late 1980s. However, early applications of interventional MRI (iMRI) were limited owing to the lack of dedicated iMRI magnets, pulse sequences, and equipment. During the 3 decades that followed, technologic advancements in iMRI magnets that balance bore access and field strength, combined with the development of rapid MRI pulse sequences, surface coils, and commercially available MR-conditional devices, led to the rapid expansion of clinical iMRI applications, particularly in the field of body iMRI. iMRI offers several advantages, including superior soft-tissue resolution, ease of multiplanar imaging, lack of ionizing radiation, and capability to re-image the same section. Disadvantages include longer examination times, lack of MR-conditional equipment, less operator familiarity, and increased cost. Nonetheless, MRI guidance is particularly advantageous when the disease is best visualized with MRI and/or when superior soft-tissue contrast is needed for treatment monitoring. Safety in the iMRI environment is paramount and requires close collaboration among interventional radiologists, MR physicists, and all other iMRI team members. The implementation of risk-limiting measures for personnel and equipment in MR zones III and IV is key. Various commercially available MR-conditional needles, wires, and biopsy and ablation devices are now available throughout the world, depending on the local regulatory status. As such, there has been tremendous growth in the clinical applications of body iMRI, including localization of difficult lesions, biopsy, sclerotherapy, and cryoablation and thermal ablation of malignant and nonmalignant soft-tissue neoplasms. Online supplemental material is available for this article. ©RSNA, 2021.

Single-Dose Neoadjuvant AKT Pathway Inhibitor Reduces Growth of Hepatocellular Carcinoma after Laser Thermal Ablation in Small-Animal Model.

BackgroundLocal recurrence following thermal ablation of hepatocellular carcinoma (HCC) larger than 2-3 cm remains a challenging clinical problem. Prior studies suggest that phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR)-dependent protein kinase B (AKT) signaling mediates HCC cell survival caused by moderate heat stress in vitro, but these findings need in vivo validation.PurposeTo test the hypothesis that neoadjuvant inhibition of PI3K/mTOR/AKT signaling reduces HCC tumor growth in vivo after laser ablation and to evaluate the effects of moderate heat stress on molecular signaling and cellular function in HCC cells in vitro.Materials and MethodsHCC tumor-bearing mice were randomized to neoadjuvant PI3K/mTOR inhibitor (BEZ235) or control groups followed by an intentional partial laser ablation or sham ablation; there were at least nine mice per group. Postablation tumor growth was monitored up to 7 days. Tumor volumes were compared for drug or ablation groups by using two-way analysis of variance. N1S1 HCC cells pretreated with BEZ235 or control and subjected to moderate heat stress (45°C for 10 minutes) or control (37°C for 10 minutes) were analyzed by using mass spectrometry. Protein interaction networks were derived from protein expression analysis software, and cellular function activation state (Z-score) and fold-change in AKT phosphorylation were calculated.ResultsThere was a 37%-75% reduction in HCC tumor volume by day 7 after ablation in the BEZ235 plus ablation group (713 mm3 ± 417) compared with vehicle plus sham (1559 mm3 ± 552), vehicle plus ablation (1041 mm3 ± 591), and BEZ235 plus sham (1108 mm3 ± 523) groups (P < .001, P = .04, and P = .005, respectively). PI3K/mTOR inhibition prevented moderate heat stress-induced AKT signaling (Z-score, -0.2; P < .001) and isoform-specific AKT phosphorylation compared with the vehicle plus heat stress group. PI3K/mTOR inhibition prevented moderate heat stress-induced global effects on HCC molecular signaling and cellular function, including decreased cell survival, growth, and proliferation (Z-score, -0.3 to -3.2; P < .001) and increased apoptosis and cell death (Z-score, 0.4-1.1; P < .001).ConclusionModerate heat stress induces PI3K/mTOR/AKT-dependent global effects on hepatocellular carcinoma (HCC) cell survival, function, and death. Neoadjuvant PI3K/mTOR/AKT inhibition reduces postablation HCC tumor growth.© RSNA, 2019Online supplemental material is available for this article.See also the editorial by White in this issue.

FIRSTT study: randomized controlled trial of uterine artery embolization vs focused ultrasound surgery.

BACKGROUND: Uterine leiomyomas (fibroid tumors) cause considerable symptoms in 30-50% of women and are the leading cause of hysterectomy in the United States. Women with uterine fibroid tumors often seek uterine-preserving treatments, but comparative effectiveness trials are lacking. OBJECTIVE: The purpose of this study was to report treatment effectiveness and ovarian function after uterine artery embolization vs magnetic resonance imaging-guided focused ultrasound surgery from the Fibroid Interventions: Reducing Symptoms Today and Tomorrow study. STUDY DESIGN: The Fibroid Interventions: Reducing Symptoms Today and Tomorrow study, which is a randomized controlled trial of uterine artery embolization vs magnetic resonance imaging-guided focused ultrasound surgery, enrolled premenopausal women with symptomatic uterine fibroid tumors; women who declined randomization were enrolled in a parallel observational cohort. A comprehensive cohort design was used for outcomes analysis. Our target enrollment was 220 women, of which we achieved 41% (n=91) in the randomized and parallel arms of the trial. Primary outcome was reintervention for uterine fibroid tumors within 36 months. Secondary outcomes were change in serum anti-Müllerian hormone levels and standardized measures of fibroid symptoms, quality of life, pain, and sexual function. RESULTS: From 2010-2014, 83 women (mean age, 44.4 years) were treated in the comprehensive cohort design (43 for magnetic resonance imaging-guided focused ultrasound surgery [27 randomized]; 40 for uterine artery embolization [22 randomized]); baseline clinical and uterine characteristics were similar between treatment arms, except for higher fibroid load in the uterine artery embolization arm. The risk of reintervention was higher with magnetic resonance imaging-guided focused ultrasound surgery than uterine artery embolization (hazard ratio, 2.81; 95% confidence interval, 1.01-7.79). Uterine artery embolization showed a significantly greater absolute decrease in anti-Müllerian hormone levels at 24 months compared with magnetic resonance imaging-guided focused ultrasound surgery. Quality of life and pain scores improved in both arms but to a greater extent in the uterine artery embolization arm. Higher pretreatment anti-Müllerian hormone level and younger age at treatment increased the overall risk of reintervention. CONCLUSION: Our study demonstrates a lower reintervention rate and greater improvement in symptoms after uterine artery embolization, although some of the effectiveness may come through impairment of ovarian reserve. Both pretreatment anti-Müllerian hormone level and age are associated with risk of reintervention. CLINICAL TRIAL REGISTRATION NUMBER: NCT00995878, clinicaltrials.gov.

Heat Stress and Hepatic Laser Thermal Ablation Induce Hepatocellular Carcinoma Growth: Role of PI3K/mTOR/AKT Signaling.

Purpose To determine if heat stress and hepatic laser thermal ablation induce hepatocellular carcinoma (HCC) growth and to identify growth factors induced by heat stress. Materials and Methods Non-heat-stressed HCC cells were cocultured with HCC cells or hepatocytes that were heat stressed at 37°C (physiologic), 45°C (moderate), or 50°C (severe) for 10 minutes and proliferation monitored with bioluminescence imaging for up to 6 days after heat stress (three experiments). Rats bearing orthotopic N1S1 HCC were randomly assigned to undergo immediate sham or laser thermal (3 W for 60 or 90 seconds; hereafter, 3W×60s and 3W×90s, respectively) ablation of the median (local) or left (distant) hepatic lobe, and tumor growth was monitored with magnetic resonance imaging for up to 18 days after ablation (six or more rats per group). Experiments were repeated with rats randomly assigned to receive either the adjuvant phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitor (NVP-BEZ235) or the vehicle control. Heat-stressed HCC cells and hepatocytes were analyzed by using microarray or quantitative real-time polymerase chain reaction analysis for growth factor expression (three or more experiments). Groups were compared by using one- or two-way analysis of variance, and post hoc pairwise comparison was performed with the Dunnett test. Results There were more non-heat-stressed HCC cells when cells were cocultured with cells subjected to moderate but not physiologic or severe heat stress (P < .001 for both). Local intrahepatic N1S1 tumors were larger at day 18 in the 3W×60s (mean, 3102 mm3 ± 463 [standard error]; P = .004) and 3W×90s (mean, 3538 mm3 ± 667; P < .001) groups than in the sham group (mean, 1363 mm3 ± 361) but not in distant intrahepatic tumors (P = .31). Adjuvant BEZ235 resulted in smaller N1S1 tumors in the BEZ235 and laser thermal ablation group than in the vehicle control and laser thermal ablation group (mean, 1731 mm3 ± 1457 vs 3844 mm3 ± 2400, P < .001). Moderate heat stress induced expression of growth factors in HCC cells and hepatocytes, including heparin-binding growth factor, fibroblast growth factor 21, and nerve growth factor (range, 2.9-66.9-fold; P < .05). Conclusion Moderate heat stress and laser thermal ablation induce hepatocellular carcinoma growth, which is prevented with adjuvant PI3K/mTOR/protein kinase B inhibition.

Heat Stress and Thermal Ablation Induce Local Expression of Nerve Growth Factor Inducible (VGF) in Hepatocytes and Hepatocellular Carcinoma: Preclinical and Clinical Studies.

The purposes of this study were to test the hypothesis that heat stress and hepatic thermal ablation induce nerve growth factor inducible (VGF) and to determine intrahepatic versus systemic VGF expression induced by thermal ablation in vivo and in patients. Hepatocytes and HCC cells were subjected to moderate (45°C) or physiologic (37°C) heat stress for 10 min and assessed for VGF expression at 0-72 h post-heat stress (n ≥ 3 experiments). Orthotopic N1S1 HCC-bearing rats were randomized to sham or laser thermal ablation (3 W × 90 s), and liver/serum was harvested at 0-7 days postablation for analysis of VGF expression (n ≥ 6 per group). Serum was collected from patients undergoing thermal ablation for HCC (n = 16) at baseline, 3-6, and 18-24 h postablation and analyzed for VGF expression. Data were analyzed using ordinary or repeated-measures one-way analysis of variance and post hoc pairwise comparison with Dunnett's test. Moderate heat stress induced time-dependent VGF mRNA (3- to 15-fold; p < 0.04) and protein expression and secretion (3.1- to 3.3-fold; p < 0.05). Thermal ablation induced VGF expression at the hepatic ablation margin at 1 and 3 days postablation but not remote from the ablation zone or distant intrahepatic lobe. There was no detectable serum VGF following hepatic thermal ablation in rats and no increase in serum VGF following HCC thermal ablation in patients at 3-6 and 18-24 h postablation compared to baseline (0.71- and 0.63-fold; p = 0.27 and p = 0.16, respectively). Moderate heat stress induces expression and secretion of VGF in HCC cells and hepatocytes in vitro, and thermal ablation induces local intrahepatic but not distant intrahepatic or systemic VGF expression in vivo.

Heat stress induced, ligand-independent MET and EGFR signalling in hepatocellular carcinoma.

PURPOSE: The aims of the present study were 2-fold: first, to test the hypothesis that heat stress induces MET and EGFR signalling in hepatocellular carcinoma (HCC) cells and inhibition of this signalling decreases HCC clonogenic survival; and second, to identify signalling pathways associated with heat stress induced MET signalling. MATERIALS AND METHODS: MET+ and EGFR+ HCC cells were pre-treated with inhibitors to MET, EGFR, PI3K/mTOR or vehicle and subjected to heat stress or control ± HGF or EGF growth factors and assessed by colony formation assay, Western blotting and/or quantitative mass spectrometry. IACUC approved partial laser thermal or sham ablation was performed on orthotopic N1S1 and AS30D HCC tumours and liver/tumour assessed for phospho-MET and phospho-EGFR immunostaining. RESULTS: Heat-stress induced rapid MET and EGFR phosphorylation that is distinct from HGF or EGF in HCC cells and thermal ablation induced MET but not EGFR phosphorylation at the HCC tumour ablation margin. Inhibition of the MET and EGFR blocked both heat stress and growth factor induced MET and EGFR phosphorylation and inhibition of MET decreased HCC clonogenic survival following heat stress. Pathway analysis of quantitative phosphoproteomic data identified downstream pathways associated with heat stress induced MET signalling including AKT, ERK, Stat3 and JNK. However, inhibition of heat stress induced MET signalling did not block AKT signalling. CONCLUSIONS: Heat-stress induced MET and EGFR signalling is distinct from growth factor mediated signalling in HCC cells and MET inhibition enhances heat stress induced HCC cell killing via a PI3K/AKT/mTOR-independent mechanism.

Targeted Prostate Biopsy and MR-Guided Therapy for Prostate Cancer.

In 2018, the American Cancer Society (ACS) estimates that 164,690 new cases of prostate cancer will be diagnosed and 29,430 will die due to the prostate cancer in the United States (Siegel et al., CA Cancer J Clin 67:7-30, 2018). Many men with prostate cancer are often managed with aggressive therapy including radiotherapy or surgery. No matter how expertly done, these therapies carry significant risk and morbidity to the patient's health related quality of life with impact on sexual, urinary and bowel function (Potosky et al., J Natl Cancer Inst 96:1358-1367, 2004). A recent meta-analysis of 19 studies reviewing the use of surgery and radiation for prostate cancer demonstrated patients who received radiation were more likely to die from their disease as compared to surgery (Wallis et al., Eur Urol 70:21-30, 2016). Furthermore, screening programs using prostatic specific antigen (PSA) and transrectal ultrasound (TRUS) guided systematic biopsy have identified increasing numbers of low risk, low grade "localized" prostate cancer. This indolent nature of many prostate cancers presents a difficult decision of when to intervene given the possible comorbidities of aggressive treatment. Active surveillance has been increasingly instituted in order to balance cancer control versus treatment side effects (Jemal et al., CA Cancer J Clin 56:106-130, 2006). Although active debate continues on the suitability of focal or regional therapy for these low or intermediate risk prostate cancer patients, many unresolved issues remain which complicate this approach of management. Some of the largest unresolved issues are: prostate cancer multifocality, limitations of current biopsy strategies, suboptimal staging by accepted imaging modalities, less than robust prediction models for indolent prostate cancers and whether established curative therapies can be safely and effectively used following focal therapy for prostate cancer. In spite of these restrictions focal therapy continues to confront the current paradigm of therapy for low and even intermediate risk disease (Onik, Tech Vasc Interv Radiol 10:149-158, 2017). It has been proposed that early detection and proper characterization may play a role in preventing the development of metastatic disease (Vickers et al., BMJ 346:f2023, 2013). There is Level 1 evidence supporting detection and subsequent aggressive treatment of intermediate and high-risk prostate cancer (Bill-Axelson et al., N Engl J Med 370:932-942, 2014). Therefore accurate assessment of cancer risk (i.e. grade and stage) using imaging and targeted biopsy is critical. Advances in prostate imaging with MRI have been accompanied with advances in MR guided therapy propelling prostate treatment solutions forward faster than ever.

Periprocedural outcomes comparing fibroid embolization and focused ultrasound: a randomized controlled trial and comprehensive cohort analysis.

BACKGROUND: Uterine fibroids are a common problem for reproductive-aged women, yet little comparative effectiveness research is available to guide treatment choice. Uterine artery embolization and magnetic resonance imaging-guided focused ultrasound surgery are minimally invasive therapies approved by the US Food and Drug Administration for treating symptomatic uterine fibroids. The Fibroid Interventions: Reducing Symptoms Today and Tomorrow study is the first randomized controlled trial to compare these 2 fibroid treatments. OBJECTIVE: The objective of the study was to summarize treatment parameters and compare recovery trajectory and adverse events in the first 6 weeks after treatment. STUDY DESIGN: Premenopausal women with symptomatic uterine fibroids seen at 3 US academic medical centers were enrolled in the randomized controlled trial (n = 57). Women meeting identical criteria who declined randomization but agreed to study participation were enrolled in a nonrandomized parallel cohort (n = 34). The 2 treatment groups were analyzed by using a comprehensive cohort design. All women undergoing focused ultrasound and uterine artery embolization received the same postprocedure prescriptions, instructions, and symptom diaries for comparison of recovery in the first 6 weeks. Return to work and normal activities, medication use, symptoms, and adverse events were captured with postprocedure diaries. Data were analyzed using the Wilcoxon rank sum test or χ2 test. Multivariable regression was used to adjust for baseline pain levels and fibroid load when comparing opioid medication, adverse events, and recovery time between treatment groups because these factors varied at baseline between groups and could affect outcomes. Adverse events were also collected. RESULTS: Of 83 women in the comprehensive cohort design who underwent treatment, 75 completed postprocedure diaries. Focused ultrasound surgery was a longer procedure than embolization (mean [SD], 405 [146] vs 139 [44] min; P <.001). Of women undergoing focused ultrasound (n = 43), 23 (53%) underwent 2 treatment days. Immediate self-rated postprocedure pain was higher after uterine artery embolization than focused ultrasound (median [interquartile range], 5 [1-7] vs 1 [1-4]; P = .002). Compared with those having focused ultrasound (n = 39), women undergoing embolization (n = 36) were more likely to use outpatient opioid (75% vs 21%; P < .001) and nonsteroidal antiinflammatory medications (97% vs 67%; P < .001) and to have a longer median (interquartile range) recovery time (days off work, 8 [6-14] vs 4 [2-7]; P < .001; days until return to normal, 15 [10-29] vs 10 [10-15]; P = .02). There were no significant differences in the incidence or severity of adverse events between treatment arms; 86% of adverse events (42 of 49) required only observation or nominal treatment, and no events caused permanent sequelae or death. After adjustment for baseline pain and uterine fibroid load, uterine artery embolization was still significantly associated with higher opioid use and longer time to return to work and normal activities (P < .001 for each). Results were similar when restricted to the randomized controlled trial. CONCLUSION: Women undergoing uterine artery embolization have longer recovery times and use more prescription medications, but women undergoing focused ultrasound have longer treatment times. These findings were independent of baseline pain levels and fibroid load.

Fibroid interventions: reducing symptoms today and tomorrow: extending generalizability by using a comprehensive cohort design with a randomized controlled trial.

BACKGROUND: Uterine fibroids are an important source of morbidity for reproductive-aged women. Despite an increasing number of alternatives, hysterectomies account for about 75% of all fibroid interventional treatments. Evidence is lacking to help women and their health care providers decide among alternatives to hysterectomy. Fibroid Interventions: Reducing Symptoms Today and Tomorrow (NCT00995878, clinicaltrials.gov) is a randomized controlled trial to compare the safety, efficacy, and economics of 2 minimally invasive alternatives to hysterectomy: uterine artery embolization and magnetic resonance imaging-guided focused ultrasound surgery. Although randomized trials provide the highest level of evidence, they have been difficult to conduct in the United States for interventional fibroid treatments. Thus, contemporaneously recruiting women declining randomization may have value as an alternative strategy for comparative effectiveness research. OBJECTIVE: We sought to compare baseline characteristics of randomized participants with nonrandomized participants meeting the same enrollment criteria and to determine whether combining the 2 cohorts in a comprehensive cohort design would be useful for analysis. STUDY DESIGN: Premenopausal women with symptomatic uterine fibroids seeking interventional therapy at 3 US academic medical centers were randomized (1:1) in 2 strata based on calculated uterine volume (<700 and ≥700 cc(3)) to undergo embolization or focused ultrasound surgery. Women who met the same inclusion criteria but declined randomization were offered enrollment in a parallel cohort. Both cohorts were followed up for a maximum of 36 months after treatment. The measures addressed in this report were baseline demographics, symptoms, fibroid and uterine characteristics, and scores on validated quality-of-life measures. RESULTS: Of 723 women screened, 57 were randomized and 49 underwent treatment (27 with focused ultrasound and 22 with embolization). Seven of the 8 women randomized but not treated were assigned to embolization. Of 34 women in the parallel cohort, 16 elected focused ultrasound and 18 elected embolization. Compared with nonrandomized participants, randomized participants had higher mean body mass index (28.7 vs 25.3 kg/m(2); P = .01) and were more likely to be gravid (77% vs 47%; P = .003) and smokers (42% vs 12%; P = .003). Age, race, uterine volume, number of fibroids, and baseline validated measures of general and disease-specific quality of life, pain, depression, and sexual function did not differ between the groups. When we performed a comprehensive cohort analysis and analyzed by treatment arm, the only baseline difference observed was a higher median McGill Pain Score among women undergoing focused ultrasound (10.5 vs 6; P = .03); a similar but nonsignificant trend was seen in visual analog scale scores for pain (median, 39.0 vs 24.0; P = .06). CONCLUSION: Using a comprehensive cohort analysis of study data could result in additional power and greater generalizability if results are adjusted for baseline differences.

MRI-Guided Prostate Interventions.

OBJECTIVE: The objective of this study is to discuss the use of MRI-guided and MRI-directed prostate biopsy techniques, describe how interventional MRI focal therapies are used for the treatment of prostate cancer, and predict future directions in prostate interventional MRI. The prospect of establishing a center for prostate imaging, diagnosis, and treatment is also discussed. CONCLUSION: Low- or intermediate-risk prostate cancer can be safely treated with MRI-compatible devices and techniques such as biopsy, cryoablation, high-intensity focused ultrasound, or focal laser ablation performed from a transrectal or transperineal approach. Although the long-term effectiveness of focal therapy for prostate cancer is unknown, the effect on urinary or sexual function is extremely low. These procedures are attracting an increasing number of men who view focal therapies as a better alternative to the uncertainty of no therapy and the more radical whole-gland surgical and radiation therapies with their higher complication rates.

Magnetic resonance imaging-guided laser interstitial thermal therapy for previously treated hypothalamic hamartomas.

OBJECTIVE Hypothalamic hamartomas (HHs) are associated with gelastic seizures and the development of medically refractory epilepsy. Magnetic resonance imaging-guided laser interstitial thermal therapy (MRg-LITT) is a minimally invasive ablative treatment that may have applicability for these deep-seated lesions. Here, the authors describe 3 patients with refractory HHs who they treated with MRg-LITT. METHODS An institutional review board-approved prospective database of patients undergoing Visualase MRg-LITT was retrospectively reviewed. Demographic and historical medical data, including seizure and medication histories, previous surgeries, procedural details, and surgical complications, along with radiological interpretation of the HHs, were recorded. The primary outcome was seizure freedom, and secondary outcomes included medication reduction, seizure frequency, operative morbidity, and clinical outcome at the latest follow-up. RESULTS All 3 patients in the multi-institutional database had developed gelastic seizures related to HH at the ages of 7, 7, and 9 years. They presented for further treatment at 25, 28, and 48 years of age, after previous treatments with stereotactic radiosurgery in all cases and partial hamartoma resection in one case. One ablation was complicated by a small tract hemorrhage, which was stable on postoperative imaging. One patient developed hyponatremia and experienced weight gain, which were respectively managed with fluid restriction and counseling. At the most recent follow-up at a mean of 21 months (range 1-32 months), one patient was seizure free while another had meaningful seizure reduction. Medication was reduced in one case. CONCLUSIONS Adults with gelastic seizures despite previous treatments can undergo MRg-LITT with reasonable safety and efficacy. This novel therapy may provide a minimally invasive alternative for primary and recurrent HH as the technique is refined.