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Rationale and Objectives: To compare thermal dosimetry metrics for specified diameters of coagulation achieved using three different ablation energy sources.Materials and Methods: 204 ablations measuring 20, 30, or 40 +/- 2 mm were created in an ex-vivo bovine liver model using 1) 2.5 cm cluster RF electrodes (n = 114), 2) 3 cm microwave antennas (n = 45), and 3) 3 cm laser diffusing fibers (n = 45). Continuous temperature monitoring was performed 5-20 mm from the applicators to calculate: a) the area under the curve (AUC), b) cumulative equivalent minutes at 43 degrees C (CEM43), and c) Arrhenius damage integral (Omega) for the critical ablation margin (DOC), with results compared by multivariate analysis of variance and regression analysis.Results: The end temperatures at the margin of coagulation varied, and was lowest for the RF cluster electrode (33-58 degrees C), higher for laser (52-72 degrees C), and covered the widest range for microwave (42-95 degrees C). These end temperatures correlated with applied energy, as linear functions (r(2) = 0.74-0.96). The total heat needed to achieve ablation (AUC) varied with applied energy and coagulation diameter as negative exponential (RF and laser) or negative power (microwave) functions (r(2) = 0.82-0.98). Similarly, CEM43 values varied exponentially with energy and distance (r(2) = 0.52-0.76) over a wide range of values (10(12)). Likewise, Omega varied not only based upon energy source and DOC, but also as a positive linear correlation to applied energy and with sigmoid correlation to duration of ablation (r(2) = 0.85-0.97).Conclusion: Our study demonstrates that the thermal dosimetry of ablation is not based solely on a fixed end temperature at the margin of the coagulation zone. Thermal dosimetry is not constant, but dependent on the type and amount of energy applied and distance suggesting the need to take into account the rate of heat transfer for ablation dosimetry. [ABSTRACT FROM AUTHOR]

Objective: To demonstrate the usefulness of real-time guidance with CT fluoroscopy to improve the yield of transbronchial needle aspiration (TBNA).Design: Prospective, observational.Setting: A tertiary-care, university-affiliated medical center.Methods: From December 1998 to April 2000, 35 patients underwent CT fluoroscopy-guided TBNA. Patients with subcarinal and precarinal lymph nodes were only included if a previous attempt was nondiagnostic, as the initial yield in this setting with conventional TBNA is high. TBNA was performed using standard technique in a CT-scan suite. Needle location was confirmed with fluoroscopy without IV contrast being used. Specimens were evaluated on-site for adequacy.Results: The procedure had to be aborted in three patients before TBNA could be performed. Samples were obtained in 32 patients. Samples were nondiagnostic in four patients. Adequate tissue was obtained in 28 of 32 patients (87.5%). Twenty-two patients had a specific benign or malignant diagnosis made, and 6 patients had lymphocytes only on the specimen. In follow-up, only one of these six patients proved to have a malignancy. All procedures were performed within a regular interventional CT time slot of 1 h. No TBNA side effects were noted.Conclusion: TBNA under CT fluoroscopic guidance is easy to perform. The yield in all accessible lymph node stations is high. [ABSTRACT FROM AUTHOR]

Purpose: To assess immunogenic effects in unembolized contralateral tumor after single lobar yttrium-90 transarterial radioembolization ( 90 Y-TARE) of colorectal liver metastases (CRLMs)., Material and Methods: The analysis comprised 10 patients with microsatellite stable (MSS) CRLM scheduled for staged treatment in the prospective AROMA trial. Eligibility criteria included bilobar metastatic disease with >5 lesions without any treatment within 3 weeks. Baseline biopsy was followed by initial 90 Y-TARE treatment of 1 liver lobe, followed by a second biopsy of yet untreated tumors in the other liver lobe at a median of 13 days (range, 4-49 days) immediately before second treatment. Tumor biopsies and peripheral blood mononuclear cells (PBMCs) were collected before treatments for immune cell analysis. Patients were stratified into responders and nonresponders based on tumor control or progression during follow-up., Results: At baseline, responders (n = 4) displayed lower concentrations of FoxP3 + cells and colocation of CD4 + FoxP3 + cells than nonresponders (both P = .02) in tumor tissues. At second biopsy, nonresponders showed a higher CD68 + macrophage density (P = .0014) than responders. Responders displayed fewer CD4 + FoxP3 + T cells than CD8 + T cells at all time points (P = .02 and P = .0428). Nonresponders demonstrated a trending increase in CD68 + macrophages (P = .062), as well as a higher CD8 + PD1 + /CD8 + ratio (P = .062). PBMCs of nonresponders displayed lower CD8 + PD1 + T cells and CD8 + PD1 + /CD8 + ratio at both time points., Conclusions: 90 Y-TARE induces local immunogenic effects in nonexposed MSS CRLM, as well as systemic exhaustion of immune cells in nonresponders. Clinical implications such as a prognostic role or synergism of 90 Y-TARE and checkpoint inhibition in MSS CRLM warrant further investigation., (Copyright © 2024 SIR. Published by Elsevier Inc. All rights reserved.)

Purpose: Low mono-energetic CT has been shown to improve visualization of acute abdominal inflammatory processes. We aimed to determine its utility in patients with acute cholecystitis and potential added value in clinical decision making., Methods: Sixty-seven consecutive patients with radiological signs of cholecystitis on contrast-enhanced dual-layer CT imaging were retrospectively identified over a four-year period (2/17-8/21). A ranked Likert scale was created for imaging findings present in acute cholecystitis, including gallbladder mucosal integrity and enhancement and pericholecystic liver parenchymal enhancement. These rankings were correlated with laboratory data, followed by sensitivity, specificity, and odds-ratios calculations., Results: Mucosal integrity and pericholecystic liver enhancement were better seen on low-energetic images by unanimous consensus. Presence of pericholecystic liver enhancement and poorer mucosal wall integrity correlated with positive bile cultures (sensitivity: 93.8 % and 96.9 %, specificity: 37.5 and 50.0 %; odds-ratio: 9.0[1.1-68.1 95 %CI] and 31.0 [2.7-350.7 95 %CI], p = 0.017 and p ≤ 0.001) in patients undergoing cholecystostomy (n = 40/67). Moreover, binary regression modeling showed that the strongest predictor variable for bile culture positivity was the score for pericholecystic liver enhancement (Exp(B) = 0.6, P = 0.022). By contrast, other laboratory markers and other imaging findings (such as GB wall thickness) showed lower sensitivities (76-82 %), specificities (16-21 %) and odds ratios (0.2-4.4) for the prediction of infected bile., Conclusions: Pericholecystic liver enhancement and gallbladder wall integrity are better visualized on low-DECT images. These findings also potentially predict bile culture positivity in patients with cholecystitis, which may influence clinical management including the need for intervention., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Adam Nevo - no disclosures. S. Nahum Goldberg- is a consultant to Angiodynamics, Cosman Company, and Xact Robotics. Gili Dar - no disclosures. Marron Daud - no disclosures. Shiran Levy - no disclosures. Jacob Sosna- is a consultant Xact, Research grants from Philips Healthcare. Naama Lev-Cohain- no disclosures., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: To perform qualitative and quantitative evaluation of low-monoenergetic images (50 KeV) compared with conventional images (120 kVp) in pulmonary embolism (PE) studies and to determine the extent and clinical relevance of these differences as well as radiologists' preferences., Materials and Methods: One hundred fifty CT examinations for PE detection conducted on a single-source dual-energy CT were retrospectively evaluated. Attenuation, contrast-to-noise-ratio, and signal-to-noise-ratio were obtained in a total of 8 individual pulmonary arteries on each exam-including both central (450/1200=37.5%) and peripheral (750/1200=62.5%) locations. Results were compared between the conventional and low-monoenergetic images. For quality assessment, 41 images containing PE were presented side-by-side as pairs of slices in both conventional and monoenergetic modes and evaluated for ease in embolus detection by 9 radiologists: cardiothoracic specialists (3), noncardiothoracic specialists (3), and residents (3). Paired samples t tests, a-parametric Wilcoxon test, McNemar test, and kappa statistics were performed., Results: Monoenergetic images had an overall statistically significant increased average ratio of 2.09 to 2.26 ( P <0.05) for each measured vessel attenuation, with an increase in signal-to-noise ratio (23.82±9.29 vs. 11.39±3.2) and contrast-to-noise ratio (17.17±6.7 vs 7.27±2.52) ( P <0.05). Moreover, 10/150 (6%) of central pulmonary artery measurements considered suboptimal on conventional mode were considered diagnostic on the monoenergetic images (181±14.6 vs. 387.7±72.4 HU respectively, P <0.05). In the subjective evaluation, noncardiothoracic radiologists showed a preference towards low-monoenergetic images, whereas cardiothoracic radiologists did not (74.4% vs. 57.7%, respectively, P <0.05)., Conclusions: The SNR and CNR increase on monoenergetic images may have clinical significance particularly in the setting of sub-optimal PE studies. Noncardiothoracic radiologists and residents prefer low monoenergetic images., Competing Interests: J.S. is a consultant Xact, Research grants from Philips Healthcare. S.N.G. is a consultant to Angiodynamics, Cosman Company, and Xact Robotics. Z.R. is an employee of Philips Healthcare. The scientific guarantor of this publication is J.S. One of the authors has significant statistical expertise: S.N.G. The remaining authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Purpose: To determine the potential prognostic value of proliferation and angiogenesis plasma proteins following CT-guided high dose rate brachytherapy (HDR-BT) of hepatocellular carcinoma (HCC)., Materials and Methods: For this prospective study, HDR-BT (1 × 15 Gy) was administered to 24 HCC patients. Plasma was obtained and analyzed using an Olink proteomics Target-96 immuno-oncology-panel that included multiple markers of angiogenesis and proliferation. Fold-change (FC) ratios were calculated by comparing baseline and 48 h post HDR-BT paired samples. Patients were classified as responders (n = 12) if they had no local progression within 6 months or systemic progression within 2 years. Non-responders (n = 12) had recurrence within 6 months and/or tumor progression or extrahepatic disease within 2 years., Results: Proliferation marker EGF was significantly elevated in non-responders compared to responders (p = 0.0410) while FGF-2, HGF, and PlGF showed no significant differences. Angiogenesis markers Angiopoietin-1 and PDGF-B were likewise significantly elevated in non-responders compared to responders (p = 0.0171, p = 0.0462, respectively) while Angiopoietin-2, VEGF-A, and VEGFR-2 did not differ significantly. Kaplan-Meier analyses demonstrated significantly shorter time to systemic progression in patients with increased EGF and Angiopoietin-1 (p = 0.0185, both), but not in patients with one of the remaining proteins elevated (all p > 0.1). Pooled analysis for these 9 proteins showed significantly shorter time to systemic progression for FC ≥1.3 and ≥1.5 for at least 3 proteins elevated (p = 0.0415, p = 0.0193, respectively)., Conclusion: Increased plasma levels of EGF and Angiopoietin-1 after HDR-BT for HCC are associated with poor response and may therefore function as predictive biomarkers of outcome., Competing Interests: Declaration of competing interest The work of Shraga Nahum Goldberg was supported by the Israeli Science Foundation [grant number 904/2020]. All the other authors do not have to declare conflict of interests., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: Combined treatment of ablation and chemoembolization for hepatocellular carcinoma represents a promising therapy to increase treatment efficacy and improve patient survival. The "hug sign" is a recently introduced radiological sign consisting in deposition of beads/contrast agent during transarterial chemoembolization in the hyperemic area surrounding the post-ablation volume, seen during intraprocedural unenhanced cone-beam CT, that may indicate intraprocedural success. Aim of our retrospective study was to analyze the usefulness of the "hug sign" at the intraprocedural unenhanced cone-beam CT as an early predictor of response to combined treatment, based on the hug sign angle., Materials and Methods: Between January 2017 and September 2021 all patients with hepatocellular carcinoma which underwent a combined treatment of thermal ablation followed by chemoembolization were enrolled. All treated patients underwent immediate post-procedural unenhanced cone-beam CT to evaluate the deposition of contrast agent, lipiodol or radiopaque beads and to assess the percentage of coverage of the ablated area with the contrast agent (hug sign angle). Patients with missing pre-procedural, intra-procedural and/or post-procedural data/imaging, or with poor-quality post-procedural cone-beam CT images were excluded., Results: 128 patients (mean age, 69.3 years ± 1.1 [standard deviation]; 87 men) were evaluated. Our study evidenced that 84.4% (81/85) of patients with a hug sign angle of 360° had no residual tumor at the first 1-/3-months follow-up examination. A hug sign angle of 360° also showed to be an independent protective factor against residual tumor at multivariate analysis., Conclusion: Unenhanced cone-beam CT performed at the end of a combined treatment with ablation plus chemoembolization can effectively predict an early treatment response on radiological images, when a hug sign angle of 360° was detected., (© 2024. The Author(s).)

Background: OBJECTIVES: To determine optimal window settings for conspicuity of abdominal inflammatory processes on 50 keV low-monoenergetic images derived from dual-energy spectral CT (DECT)., Methods: A retrospective study of 30 patients with clinically proven pancreatitis (15/30) or pyelonephritis (15/30) with inflammatory lesions visible on DECT scans were selected to serve as reference populations. 50 keV low-monoenergetic images in the portal venous phase were iteratively evaluated by 6 abdominal radiologists in twenty-one different windows (7-350HU center; 120-580HU width), selected using a simplex optimization algorithm. Each reader graded the conspicuity of the parenchymal hypodense lesions and image background quality. Three-dimensional contour maps expressing the relationship between overall reader grade and window center and width were constructed and used to find the ideal window for inflammatory pancreatic and renal processes and the image background quality. Finally, 15 appendicitis cases were reviewed on optimal pancreas and kidney windows and the manufacturer recommended conventional abdominal window settings for conventional imaging., Results: Convergence to optimal windowing was achieved based upon a total of 3,780 reads (21 window settings × 6 readers × 15 cases for pancreas and kidney). Highest conspicuity grade (>4.5 ± 0.0) for pancreas inflammatory lesions was seen at 116HU/430HU, whereas hypodense pyelonephritis had highest conspicuity at 290HU/570HU. This rendered an ideal "compromise" window (>4 ± 0.2) of 150HU/450HU which differed substantially from conventional manufacturer recommended settings of 50HU/380HU (2.1 ± 1.0, p = 0.00001). Appendix mucosal enhancement was best visualized at manufacturer settings., Conclusions: Optimal visualization of inflammatory processes in abdominal organs on 50 keV low-monoenergetic images may require tailored refinement of window settings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: Microwave ablation (MWA) is a treatment modality for colorectal liver metastases (CRLM). While potentially curative, more information is needed on factors that contribute to long-term local tumour control. The prospective multicentre observational study CIRSE Emprint Microwave Ablation Registry aims to prospectively collect real-world technical data and clinical outcomes on patients treated with MWA in CRLM., Methods: Eligible patients are adults with up to 9 local treatment naïve CRLM of ≤ 3 cm completely treatable with either MWA alone or MWA with resection and/or radiotherapy within 8 weeks. Data are collected, at baseline, every 3 months until 12 months, and thereafter every 6 months until the end of the study. The primary outcome measure is local tumour control. Secondary outcome measures are overall survival, (hepatic-) disease-free survival, time-to-progression untreatable by ablation, systemic therapy vacation, safety, and quality of life. Covariates related to the primary outcome measure will be assessed using a stratified log-rank test and an univariable Cox proportional hazard regression. A sample size of 500 patients with 750 lesions produces a two-sided 95% confidence interval with a precision equal to 0.057., Results: Between September 2019 and December 2022, 500 patients have been enrolled with at least 976 treated tumours., Conclusion: The prospective observational CIEMAR study will provide valuable insights into the real-world use of MWA, helping in the future patient selection and clarifying factors that may contribute to long-term local tumour control., Trial Registration: NCT03775980., (© 2023. The Author(s).)

Purpose: The role of microRNA-146a (miR-146a) in defining the tumor immune microenvironment (TIME) is well established. The aim of this study was to evaluate circulating miR-146a as an early prognostic marker of 90 Y-radioembolization ( 90 Y-RE) in metastatic liver cancer and to assess the correlation between circulating miR-146a and TIME cellular composition in distant, yet untreated metastases., Methods: Twenty-one patients with bilobar liver lesions from gastro-intestinal cancer underwent lobar 90 Y-RE. Biopsy of contralateral lobe abscopal tumors was acquired at the onset of a second treatment session at a median of 21 days after initial RE, immediately prior to ablation therapy of the contralateral lobe tumor. miR-146a was measured by RT-qPCR in plasma collected 24 h before (T1) and 48 h after (T2) initial unilobar 90 Y-RE. The level of miR-146a was correlated with the infiltration of CD4 + , CD8 + , FoxP3 T cells, CD163 + M2 macrophages and immune-exhausted T cells in the abscopal tumor tissue acquired before the second treatment session., Results: Plasma samples collected at T2 showed a higher concentration of miR-146a with respect to T1 in 43% of the patients (p = 0.002). In these patients, tumors revealed a pro-tumorigenic immune composition with enrichment of Tim3 + immune exhausted cells (p = 0.021), in combination with a higher infiltration of CD163 + M2 macrophages and a lower infiltration of CD8 + T cells. Patients with a higher level of miR-146a after 90 Y-RE showed a trend to shorter OS (p = 0.055)., Conclusion: miR-146a may represent a novel prognostic biomarker for 90 Y-radioembolization in metastatic liver cancer., (© 2023. The Author(s).)

Purpose: To characterize intratumoral immune cell trafficking in ablated and synchronous tumors following combined radiofrequency ablation (RFA) and systemic liposomal granulocyte-macrophage colony stimulation factor (lip-GM-CSF)., Methods: Phase I, 72 rats with single subcutaneous R3230 adenocarcinoma were randomized to 6 groups: a) sham; b&c) free or liposomal GM-CSF alone; d) RFA alone; or e&f) combined with blank liposomes or lip-GM-CSF. Animals were sacrificed 3 and 7 days post-RFA. Outcomes included immunohistochemistry of dendritic cells (DCs), M1 and M2 macrophages, T-helper cells (Th1) (CD4+), cytotoxic T- lymphocytes (CTL) (CD8+), T-regulator cells (T-reg) (FoxP3+) and Fas Ligand activated CTLs (Fas-L+) in the periablational rim and untreated index tumor. M1/M2, CD4+/CD8+ and CD8+/FoxP3+ ratios were calculated. Phase II, 40 rats with double tumors were randomized to 4 groups: a) sham, b) RFA, c) RFA-BL and d) RFA-lip-GM-CSF. Synchronous untreated tumors collected at 7d were analyzed similarly., Results: RFA-lip-GMCSF increased periablational M1, CTL and CD8+/FoxP3+ ratio at 3 and 7d, and activated CTLs 7d post-RFA (p<0.05). RFA-lip-GMSCF also increased M2, T-reg, and reduced CD4+/CD8+ 3 and 7d post-RFA respectively (p<0.05). In untreated index tumor, RFA-lip-GMCSF improved DCs, M1, CTLs and activated CTL 7d post-RFA (p<0.05). Furthermore, RFA-lip-GMSCF increased M2 at 3 and 7d, and T-reg 7d post-RFA (p<0.05). In synchronous tumors, RFA-BL and RFA-lip-GM-CSF improved DC, Th1 and CTL infiltration 7d post-RFA., Conclusion: Systemic liposomal GM-CSF combined with RFA improves intratumoral immune cell trafficking, specifically populations initiating (DC, M1) and executing (CTL, FasL+) anti-tumor immunity. Moreover, liposomes influence synchronous untreated metastases increasing Th1, CTL and DCs infiltration., Competing Interests: VAB has patents on the PD-1 pathway licensed by Bristol-Myers Squibb, Roche, Merck, EMD-Serono, Boehringer Ingelheim, AstraZeneca, Novartis and Dako. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The authors declare no other competing interests., (Copyright: © 2023 Moussa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: To investigate the role of microRNA-21 (miR21) in radiofrequency (RF) ablation-induced tumor growth and whether miR21 inhibition suppresses tumorigenesis., Material and Methods: Standardized liver RF ablation was applied to 35 C57/BL6 mice. miR21 and target proteins pSTAT3, PDCD4, and PTEN were assayed 3 hours, 24 hours, and 3 days after ablation. Next, 53 Balb/c and 44 C57BL/6 mice received Antago-miR21 or scrambled Antago-nc control, followed by intrasplenic injection of 10,000 CT26 or MC38 colorectal tumor cells, respectively. Hepatic RF ablation or sham ablation was performed 24 hours later. Metastases were quantified and tumor microvascular density (MVD) and cellular proliferation were assessed at 14 or 21 days after the procedures, respectively., Results: RF ablation significantly increased miR21 levels in plasma and hepatic tissue at 3 and 24 hours as well as target proteins at 3 days after ablation (P < .05, all comparisons). RF ablation nearly doubled tumor growth (CT26, 2.0 SD ± 1.0 fold change [fc]; MC38, 1.9 SD ± 0.9 fc) and increased MVD (CT26, 1.9 SD ± 1.0 fc; MC38, 1.5 ± 0.5 fc) and cellular proliferation (CT26, 1.7 SD ± 0.7 fc; MC38, 1.4 SD ± 0.5 fc) compared with sham ablation (P < .05, all comparisons). RF ablation-induced tumor growth was suppressed when Antago-miR21 was administered (CT26, 1.0 SD ± 0.7 fc; MC38, 0.9 SD ± 0.4 fc) (P < .01, both comparisons). Likewise, Antago-miR21 decreased MVD (CT26, 1.0 SD ± 0.3 fc; MC38, 1.0 SD ± 0.2 fc) and cellular proliferation (CT26, 0.9 SD ± 0.3 fc; MC38, 0.8 SD ± 0.3 fc) compared with baseline (P < .05, all comparisons)., Conclusions: RF ablation upregulates protumorigenic miR21, which subsequently influences downstream tumor-promoting protein pathways. This effect can potentially be suppressed by specific inhibition of miR21, rendering this microRNA a pivotal and targetable driver of tumorigenesis after hepatic thermal ablation., (Copyright © 2023 SIR. Published by Elsevier Inc. All rights reserved.)

Background: Metastases are the leading cause of mortality in cancer patients. Linear and parallel are the two prominent models of metastatic progression. Metastases can be detected synchronously along with the primary tumor or metachronously, following treatment of localized disease. The aim of the study was to determine whether synchronous metastases (SM) and metachronous metastases (MM) differ only in lead-time or stem from different biological processes., Materials and Methods: We retrospectively studied the chest CTs of 791 patients inflicted by eleven malignancy types that were treated in our institution in the years 2010-2020. Patient's population included 396 with SM and 395 with MM. The diameter of 15,427 lung metastases was measured. Clonal origin was deduced from the linear/parallel ratio (LPR)-a computerized analysis of metastases diameters. LPR of  1 suggests pure linear dissemination and - 1 pure parallel., Results: Patients with MM were significantly older (average of 62.9 vs 60.7 years, p = 0.02), and higher percentage of them were males (58.7% vs 51.1%, p = 0.03). Median overall survival of patients with MM and SM was remarkably similar (23 months and 26 months respectively, p = 0.774) when calculated from the time of metastases diagnosis. Parallel dissemination (LPR ≤ 0) was found in 35.4% of patients with MM compared to only 19.8% of the patients with SM (p < 0.00001)., Conclusion: Patients with SM and MM differ in demography and in clonal origin. Different therapeutic approaches may be considered in these two conditions., (© 2023. The Author(s).)

Image-guided radiofrequency ablation (RFA) is used to treat focal tumors in the liver and other organs. Despite potential advantages over surgery, hepatic RFA can promote local and distant tumor growth by activating pro-tumorigenic growth factor and cytokines. Thus, strategies to identify and suppress pro-oncogenic effects of RFA are urgently required to further improve the therapeutic effect. Here, the proliferative effect of plasma of Hepatocellular carcinoma or colorectal carcinoma patients 90 min post-RFA was tested on HCC cell lines, demonstrating significant cellular proliferation compared to baseline plasma. Multiplex ELISA screening demonstrated increased plasma pro-tumorigenic growth factors and cytokines including the FGF protein family which uniquely and selectively activated HepG2. Primary mouse and immortalized human hepatocytes were then subjected to moderate hyperthermia in-vitro, mimicking thermal stress induced during ablation in the peri-ablational normal tissue. Resultant culture medium induced proliferation of multiple cancer cell lines. Subsequent non-biased protein array revealed that these hepatocytes subjected to moderate hyperthermia also excrete a similar wide spectrum of growth factors. Recombinant FGF-2 activated multiple cell lines. FGFR inhibitor significantly reduced liver tumor load post-RFA in MDR2-KO inflammation-induced HCC mouse model. Thus, Liver RFA can induce tumorigenesis via the FGF signaling pathway, and its inhibition suppresses HCC development., (© 2023. Springer Nature Limited.)

Purpose: Biomarkers are essential to implement personalized therapies in cancer treatment options. As primary liver tumors are increasing and treatment is coupled to liver function and activation of systemic cells of the immune system, we investigated blood-based cells for their ability to predict response to local ablative therapy., Methods: We analyzed peripheral blood cells in 20 patients with primary liver cancer at baseline and following brachytherapy. In addition to platelets, leukocytes, lymphocytes, monocytes, neutrophils and most common ratios PLR, LMR, NMR and NLR, we investigated T cell and NKT cell populations of 11 responders and 9 non-responders using flow cytometry., Results: We have found a peripheral blood cell signature that differed significantly between responders and non-responders treated with interstitial brachytherapy (IBT). At baseline, non-responders featured higher numbers of platelets, monocytes and neutrophils, a higher platelet-to-lymphocyte ratio and an increase in the NKT cell population with a concurrent reduction in CD16 + NKT cells. Simultaneously, a lower percentage of CD4 + T cells was present in non-responders, as also reflected in a lower CD4/8 ratio. CD45RO + memory cells were lower in both, CD4 + and CD8 + T cell populations whereas PD-1 + T cells were only present in the CD4 + T cell population., Conclusion: Baseline blood-based cell signature may function as a biomarker to predict response following brachytherapy in primary liver cancer., (© 2023. The Author(s).)

Purpose: To perform radiofrequency (RF) ablation of hepatocellular carcinoma (HCC) and to assess serological and histopathological markers of tumorigenesis in distant untreated tumors to determine whether these were associated with unfavorable outcomes such as early relapse and increased biological aggressiveness., Materials and Methods: The study cohort comprised 13 patients from a prospective single-arm study. All patients underwent 2 ablation sessions of multifocal HCC nodules 14 days apart. Core biopsy samples of untreated tumors were acquired at baseline and at the time of the second ablation session. Samples were stained immunohistochemically with Ki-67 (proliferation) and CD34 (microvasculature). Blood plasma was obtained at baseline and 2 days after the initial ablation session and analyzed for hepatocyte growth factor (HGF), vascular endothelial growth factor C, and angiopoietin-2 using an enzyme-linked immunosorbent assay. The clinical follow-up period ranged from 7 to 25 months. Patients were stratified as responders (complete remission or limited and delayed recurrence at >6 months; n = 6) or nonresponders (any recurrence within 6 months or >3 new tumors or any new tumor of >3 cm thereafter; n = 7)., Results: In 3 of 7 nonresponders, the Ki-67 index markedly increased in untreated tumors, whereas Ki-67 was stable in all responders. Microvascular density strongly increased in a single nonresponder only. HGF and angiopoietin-2 increased by >30% in 3 of 7 and 4 of 7 nonresponders, respectively, whereas they were stable or decreased in responders. Overall, ≥2 biomarkers were elevated in 6 of 7 (85.7%) nonresponders, whereas 4 of 6 responders demonstrated no increased biomarker and 2 patients demonstrated increase in 1 biomarker only (P = .002)., Conclusions: RF ablation of HCC can produce protumorigenic factors that induce effects in distant untreated tumors. These may potentially function as biomarkers of clinical outcome., (Copyright © 2023 SIR. Published by Elsevier Inc. All rights reserved.)

Hepatocellular carcinoma represents an important cause of death worldwide. Early-stage hepatocellular carcinoma patients not suitable for surgery can be treated with a variety of minimally invasive locoregional interventional oncology techniques. Various guidelines in different countries address the treatment of hepatocellular carcinoma, but the actual treatment is usually discussed by a multidisciplinary tumor board in a personalized manner, leading to potential treatment differences based on Western and Eastern perspectives. The aim of this paper is to integrate literature evidence with the eminent experiences collected during a focused session at the Mediterranean Interventional Oncology (MIO) Live Congress 2023.

Background and Aims: Prognostic biomarkers identifying patients with early tumor progression after local ablative therapy remain an unmet clinical need. The aim of this study was to investigate circulating miR-21 and miR-210 levels as prognostic biomarkers of HCC treated by CT-guided high-dose rate brachytherapy (HDR-BT)., Materials and Methods: 24 consecutive HCC patients (BCLC A and B) treated with CT-guided HDR-BT (1 × 15 Gy) were included in this prospective IRB-approved study. RT-PCR was performed to quantify miR-21 and miR-210 levels in blood samples acquired prior to and 2 d after HDR-BT. Follow-up imaging (contrast-enhanced liver MRI and whole-body CT) was performed in 3 months follow-up intervals. Therapy response was assessed with patients classified as either responders or non-responders (12 each). Responders were defined as having no local or diffuse systemic progression within 6 months and no diffuse systemic progression exceeding 3 nodules/nodule diameter > 3 cm from 6 months to 2 years. Non-responders had recurrence within 6 months and/or tumor progression with > 3 nodules or individual lesion diameter > 3 cm or extrahepatic disease within two years, respectively. Biostatistics included parametric and non-parametric testing (Mann-Whitney-U-test), as well as Kaplan-Meier curve construction., Results: The responder group demonstrated significantly decreasing miR-21 values 2 d post therapy compared to non-responders (median miR-21 2 -ΔΔCт : responders 0.73 [IQR 0.34], non-responders 1.53 [IQR 1.48]; p = 0.0102). miR-210 did not show any significant difference between responders and non-responders (median miR-210 2 -ΔΔCт : responders 0.74 [IQR 0.45], non-responders 0.99 [IQR 1.13]; p = 0.8399). Kaplan-Meier curves demonstrated significantly shorter time to systemic progression for increased miR-21 (p = 0.0095) but not miR-210 (p = 0.7412), with events accumulating > 1 year post therapy in non-responders (median time to systemic progression 397 days)., Conclusion: Increasing circulating miR-21 levels are associated with poor response and shorter time to systemic progression in HDR-BT-treated HCC. This proof-of-concept study provides a basis for further investigation of miR-21 as a prognostic biomarker and potential stratifier in future clinical trials of interventional oncology therapies., Trial Registration: In this monocentric clinical study, we analyzed prospectively acquired data of 24 patients from the "ESTIMATE" patient cohort (Studiennummer: DRKS00010587, Deutsches Register Klinischer Studien). Ethical approval was provided by the ethics committee "Ethikkommission bei der LMU München" (reference number "17-346") on June 20, 2017 and August 26, 2020., (© 2023. The Author(s).)

Personalized cancer treatments help to deliver tailored and biologically driven therapies for cancer patients. Interventional oncology techniques are able to treat malignancies in a locoregional fashion, with a variety of mechanisms of action leading to tumor necrosis. Tumor destruction determines a great availability of tumor antigens that can be recognized by the immune system, potentially triggering an immune response. The advent of immunotherapy in cancer care, with the introduction of specific immune checkpoint inhibitors, has led to the investigation of the synergy of these drugs when used in combination with interventional oncology treatments. The aim of this paper is to review the most recent advances in the field of interventional oncology locoregional treatments and their interactions with immunotherapy.

Purpose: To establish molecular magnetic resonance (MR) imaging instruments for in vivo characterization of the immune response to hepatic radiofrequency (RF) ablation using cell-specific immunoprobes., Materials and Methods: Seventy-two C57BL/6 wild-type mice underwent standardized hepatic RF ablation (70 °C for 5 minutes) to generate a coagulation area measuring 6-7 mm in diameter. CD68 + macrophage periablational infiltration was characterized with immunohistochemistry 24 hours, 72 hours, 7 days, and 14 days after ablation (n = 24). Twenty-one mice were subjected to a dose-escalation study with either 10, 15, 30, or 60 mg/kg of rhodamine-labeled superparamagnetic iron oxide nanoparticles (SPIONs) or 2.4, 1.2, or 0.6 mg/kg of gadolinium-160 ( 160 Gd)-labeled CD68 antibody for assessment of the optimal in vivo dose of contrast agent. MR imaging experiments included 9 mice, each receiving 10-mg/kg SPIONs to visualize phagocytes using T2 ∗ -weighted imaging in a horizontal-bore 9.4-T MR imaging scanner, 160 Gd-CD68 for T1-weighted MR imaging of macrophages, or 0.1-mmol/kg intravenous gadoterate (control group). Radiological-pathological correlation included Prussian blue staining, rhodamine immunofluorescence, imaging mass cytometry, and immunohistochemistry., Results: RF ablation-induced periablational infiltration (206.92 μm ± 12.2) of CD68 + macrophages peaked at 7 days after ablation (P < .01) compared with the untreated lobe. T2 ∗ -weighted MR imaging with SPION contrast demonstrated curvilinear T2 ∗ signal in the transitional zone (TZ) (186 μm ± 16.9), corresponsing to Iron Prussian blue staining. T1-weighted MR imaging with 160 Gd-CD68 antibody showed curvilinear signal in the TZ (164 μm ± 3.6) corresponding to imaging mass cytometry., Conclusions: Both SPION-enhanced T2 ∗ -weighted and 160 Gd-enhanced T1-weighted MR imaging allow for in vivo monitoring of macrophages after RF ablation, demonstrating the feasibility of this model to investigate local immune responses., (Copyright © 2022 SIR. Published by Elsevier Inc. All rights reserved.)

Background: Oligometastatic disease (OD) is usually defined arbitrarily as a condition in which there are ≤ 5 metastases. Given limited disease, it is expected that patients with OD should have better prognosis compared to other metastatic patients and that they can potentially benefit from metastasis-directed therapy (MDT). In this study, we attempted to redefine OD based upon objective evidence that fulfill these assumptions., Methods: Chest CTSs of 773 patients with 15,947 lung metastases originating from ten malignancy types were evaluated. The number and largest diameter of each metastasis was recorded. Metastatic cluster was defined as a cluster of two or more metastases with diameter difference ≤ 1 mm. The prognostic power of seven statistical models on overall survival (OS) was analyzed., Findings: Both the number of metastases and metastatic clusters had a highly significant impact on OS (p < 0.0001, p = 0.003 respectively). Patients with a single metastasis or a single cluster of metastases (regardless of metastases number), equaling 16.2% of all patients, had significantly better prognosis compared to other patients (p = 0.0002). If metastases diameter variability is ignored, as in the standard definition of OD, then patients with 2-5 and 6-10 metastases would have a similar prognosis., Interpretation: Patients with a single cluster of metastases, theoretically originating from a single clone, have significantly better prognosis compared to patients with more than one cluster. Using this definition can potentially improve the results of MDT. The upper limit of metastases number should be determined by the technical capabilities of the MDT used., (© 2023. The Author(s).)

Interventional oncology (IO) employs image-guided techniques to perform minimally invasive procedures, providing lower-risk alternatives to many traditional medical and surgical therapies for cancer patients. Since its advent, due to rapidly evolving research development, its role has expanded to encompass the diagnosis and treatment of diseases across multiple body systems. In detail, interventional oncology is expanding its role across a wide spectrum of disease sites, offering a potential cure, control, or palliative care for many types of cancer patients. Due to its widespread use, a comprehensive review of the new indications for locoregional procedures is mandatory. This article summarizes the expert discussion and report from the "MIOLive Meet SIO" (Society of Interventional Oncology) session during the last MIOLive 2022 (Mediterranean Interventional Oncology Live) congress held in Rome, Italy, integrating evidence-reported literature and experience-based perceptions. The aim of this paper is to provide an updated review of the new techniques and devices available for innovative indications not only to residents and fellows but also to colleagues approaching locoregional treatments.

Purpose: To assess the performance and accuracy of CT-guided needle insertion for clinical biopsies using a novel, hands-free robotic system that balances accuracy with the duration of the procedure and radiation dose., Materials and Methods: A prospective, multi-center study was conducted on 60 clinically indicated biopsies of abdominal lesions at two centers (Center 1, n=26; Center 2, n=34). CT datasets were obtained for planning and controlled placement of 17g and 18g needles using a patient-mounted, CT-guided robotic system with 5 degrees of freedom. Planning included target selection, skin entry point, and predetermined checkpoints where additional imaging was performed to permit stepwise correction of the needle trajectory. Success rate, needle tip-to-target distance, number of checkpoints used, number of trajectory corrections, procedure duration, and effective radiation dose were recorded and compared between centers., Results: In 55 of 60 procedures (91.7%), the robot positioned the trocar needle successfully on target. In the remaining 5 patients, the procedure was manually performed by the operator due to technical failure (n=3) or patient-related factors (n=2). The average lesion size was 2.8 ± 1.7cm with a lesion depth from the skin of 8.7 ± 2.6cm, and there was no difference between centers. The overall accuracy (needle tip-to-target distance) was 1.71 ± 1.49 (range 0.05-7.20mm), with an accuracy of 2.06 ± 1.45 mm at Center 1 and 1.45 ± 1.52 mm at Center 2 (p=0.1358). Center 1 used significantly more checkpoints (4.96 ± 1.08) and performed target adjustments in 20 of 24 (83%) cases compared to Center 2 (2.77 ± 0.6 checkpoints and target adjustments in 13 of 31 cases, 42%) (p=0.0024). Accordingly, the steering duration from skin entry to the target varied between Centers 1 and 2; 13.1min ± 4.25min vs. 5.7min ± 2.7min, respectively (p <0.001). The average DLP for the entire procedure was 1147 ± 820 mGycm, with a slightly lower average at Center 2 (1031 ± 724 mGycm) compared to Center 1 (1297 ± 925 mGycm) (p=0.236)., Conclusion: Accurate needle-targeting within an error of 2mm can be achieved in patients using a CT-guided robotic system. The variation in the number of checkpoints did not affect system accuracy but was related to shorter steering times and may contribute to a lower radiation dose. Accurate needle insertion using a hands-free CT-guided robotic system may facilitate difficult needle placement and enhance the performance of less-experienced interventionalists.

Local ablative therapies are established treatment modalities in the treatment of early- and intermediate-stage hepatocellular carcinoma (HCC). Systemic effects of local ablation on circulating immune cells may contribute to patients' response. Depending on their activation, myeloid cells are able to trigger HCC progression as well as to support anti-tumor immunity. Certain priming of monocytes may already occur while still in the circulation. By using flow cytometry, we analyzed peripheral blood monocyte cell populations from a prospective clinical trial cohort of 21 HCC patients following interstitial brachytherapy (IBT) or radiofrequency ablation (RFA) and investigated alterations in the composition of monocyte subpopulations and monocytic myeloid-derived suppressor cells (mMDSCs) as well as receptors involved in orchestrating monocyte function. We discovered that mMDSC levels increased following both IBT and RFA in virtually all patients. Furthermore, we identified varying alterations in the level of monocyte subpopulations following radiation compared to RFA. (A) Liquid biopsy liquid biopsy of circulating monocytes in the future may provide information on the inflammatory response towards local ablation as part of an orchestrated immune response., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kimm, Kästle, Stechele, Öcal, Richter, Ümütlü, Schinner, Öcal, Salvermoser, Alunni-Fabbroni, Seidensticker, Goldberg, Ricke and Wildgruber.)

Background: Linear and parallel are the two leading models of metastatic progression. In this study we propose a simple way to differentiate between them. While the linear model predicts accumulation of genetic and epigenetic alterations within the primary tumor by founder cells before spreading as waves of metastases, the parallel model suggests preclinical distribution of less advanced disseminated tumor cells with independent selection and expansion at the ectopic sites. Due to identical clonal origin and time of dispatching, linear metastases are expected to have comparable diameters in any specific organ while parallel metastases are expected to appear in variable sizes., Methods and Findings: Retrospective revision of chest CT of oncological patients with lung metastases was performed. Metastasis number and largest diameters were recorded. The sum number of metastases with a similar diameter (c) and those without (i) was counted and the linear/parallel ratio (LPR) was calculated for each patient using the formula (∑c-∑i)/(∑c+∑i). A LPR ratio of 1 implies pure linear progression pattern and -1 pure parallel. 12,887 metastases were measured in 503 patients with nine malignancy types. The median LPR of the entire group was 0.71 (IQR 0.14-0.93). In carcinomas of the pancreas, prostate, and thyroid the median LPR was 1. Median LPRs were 0.91, 0.65, 0.60, 0.58, 0.50 and 0.43 in renal cell carcinomas, melanomas, colorectal, breast, bladder, and sarcomas, respectively., Conclusions: Metastatic spread of thyroid, pancreas, and prostate tumors is almost exclusively by a linear route. The spread of kidney, melanoma, colorectal, breast, bladder and sarcoma is both linear and parallel with increasing dominance of the parallel route in this order. These findings can explain and predict the clinical and genomic features of these tumors and can potentially be used for evaluation of metastatic origin in the individual patient., Competing Interests: None of the authors have any direct or indirect financial incentive associated with publishing the article.

Computer-aided color parameter imaging (CPI) is a novel technique for contrast-enhanced ultrasound (CEUS) that can highlight hemodynamic features of focal lesions. The purpose of the study was to investigate the role of CPI in evaluation of hepatocellular carcinoma (HCC) hemodynamic features and prognosis after radiofrequency ablation (RFA). One hundred twenty-one patients with HCC underwent CEUS with CPI analysis before RFA. Eighty-nine patients had pathologically proven well- to moderately differentiated HCC (WM-HCC), and 32 patients had poorly differentiated or undifferentiated HCC (PU-HCC). Perfusion features of CEUS and contrast-enhanced computed tomography/magnetic resonance imaging were compared with CPI parameters for WM-HCC and PU-HCC. The results indicated that 67.4% of WM-HCC had a centrifugal perfusion CPI pattern, whereas 84.4% of PU-HCC tumors had a centripetal pattern (p < 0.001, odds ratio = 11.2). The specificity, sensitivity and accuracy of the CPI perfusion pattern regarding HCC pathological grade were higher than those with routine CEUS (84.4% vs. 9.4%, p < 0.001; 67.4% vs. 3.4%, p < 0.001; 71.9% vs. 5.0%, p < 0.001). Moreover, multivariable analysis revealed that the CPI perfusion pattern was an independent risk factor for progression-free survival post-RFA (centripetal group: 28.3 ± 4.1 mo vs. centrifugal group: 45.8 ± 4.4 mo, p = 0.002). A novel CPI technique for CEUS could non-invasively provide valuable hemodynamic information and predict prognosis for HCC patients treated by RFA., (Copyright © 2022 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Radiofrequency ablation (RFA) of intrahepatic tumors induces distant tumor growth through activation of interleukin 6/signal transducer and activator of transcription 3 (STAT3)/hepatocyte growth factor (HGF)/tyrosine-protein kinase Met (c-MET) pathway. Yet, the predominant cellular source still needs to be identified as specific roles of the many types of periablational infiltrating immune cells requires further clarification. Here we report the key role of activated myofibroblasts in RFA-induced tumorigenesis and successful pharmacologic blockade. Murine models simulating RF tumorigenic effects on a macrometastatic tumor and intrahepatic micrometastatic deposits after liver ablation and a macrometastatic tumor after kidney ablation were used. Immune assays of ablated normal parenchyma demonstrated significantly increased numbers of activated myofibroblasts in the periablational rim, as well as increased HGF levels, recruitment other cellular infiltrates; macrophages, dendritic cells and natural killer cells, HGF dependent growth factors; fibroblast growth factor-19 (FGF-19) and receptor of Vascular Endothelial Growth Factor-1 (VEGFR-1), and proliferative indices; Ki-67 and CD34 for microvascular density. Furthermore, macrometastatic models demonstrated accelerated distant tumor growth at 7d post-RFA while micrometastatic models demonstrated increased intrahepatic deposit size and number at 14 and 21 days post-RFA. Multi-day atorvastatin, a selective fibroblast inhibitor, inhibited RFA-induced HGF and downstream growth factors, cellular markers and proliferative indices. Specifically, atorvastatin treatment reduced cellular and proliferative indices to baseline levels in the micrometastatic models, however only partially in macrometastatic models. Furthermore, adjuvant atorvastatin completely inhibited accelerated growth of macrometastasis and negated increased micrometastatic intrahepatic burden. Thus, activated myofibroblasts drive RF-induced tumorigenesis at a cellular level via induction of the HGF/c-MET/STAT3 axis, and can be successfully pharmacologically suppressed., Competing Interests: The authors have declared that no competing interests exist.

Background: Preclinical studies have shown that modulation of the tumor microvasculature with anti-angiogenic agents decreases tumor perfusion and may increase the efficacy of radiofrequency ablation (RFA) in hepatocellular carcinoma (HCC). Retrospective studies suggest that sorafenib given prior to RFA promotes an increase in the ablation zone, but prospective randomized data are lacking., Aims: We conducted a randomized, double-blind, placebo-controlled phase II trial to evaluate the efficacy of a short-course of sorafenib prior to RFA for HCC tumors sized 3.5-7 cm (NCT00813293)., Methods: Treatment consisted of sorafenib 400 mg twice daily for 10 days or matching placebo, followed by RFA on day 10. The primary objectives were to assess if priming with sorafenib increased the volume and diameter of the RFA coagulation zone and to evaluate its impact on RFA thermal parameters. Secondary objectives included feasibility, safety and to explore the relationship between tumor blood flow on MRI and RFA effectiveness., Results: Twenty patients were randomized 1:1. Priming with sorafenib did not increase the size of ablation zone achieved with RFA and did not promote significant changes in thermal parameters, although it significantly decreased blood perfusion to the tumor by 27.9% (p = 0.01) as analyzed by DCE-MRI. No subject discontinued treatment owing to adverse events and no grade 4 toxicity was observed., Conclusion: Priming of sorafenib did not enhance the effect of RFA in intermediate sized HCC. Future studies should investigate whether longer duration of treatment or a different antiangiogenic strategy in the post-procedure setting would be more effective in impairing tumor perfusion and increasing RFA efficacy., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives : To determine whether two-step ablation using sequential low and high temperature heating can achieve improved outcomes in animal tumor models when combined with chemotherapeutic liposomes (LP). Materials and methods : Balb/c mice bearing 4T1 tumor received paclitaxel-loaded liposomes followed 24 h later by either traditional RFA (70 °C, 5 min) or a low temperature RFA (45 °C, 5 min), or two-step RFA (45 °C 2 min + 70 °C 3 min). Intratumoral drug accumulation and bio-distribution in major organs were evaluated. Periablational drug penetration was evaluated by pathologic staining and the intratumoral interstitial fluid pressure (IFP) was measured directly. For long-term outcomes, mice bearing 4T1 or H22 tumors were randomized into five groups ( n = 8 per group): control (no treatment), RFA alone, LP + RFA (45 °C), LP + RFA (70 °C) and LP + RFA (45 + 70 °C). End-point survivals were compared among the different groups. Results : The greater intratumoral drug accumulation (3.35 ± 0.32 vs. 3.79 ± 0.29 × 10 8 phot/cm 2 /s at 24 h, p = 0.09), deeper periablational drug penetration (45.7 ± 5.0 vs. 1.6 ± 0.5, p < 0.001), and reduced off-target drug deposition in major organs (liver 96.1 ± 31.6 vs. 47.4 ± 1.5 × 10 6 phot/cm 2 /s, p < 0.001) were found when combined with RFA (45 °C) compared to drug alone. For long-term outcomes, 4T1 tumor growth rates for LP + two-step RFA (45 + 70 °C) were significantly slower than those of LP + RFA (70 °C), LP + RFA (45 °C), and RFA alone ( P < 0.01 for all comparisons). End point survival for LP + RFA (45 + 70 °C) was also longer than that for LP + RFA (70 °C) (median 16 vs. 10 days, p = 0.003) or LP + RFA 45 °C (11 days, p = 0.009) and RFA alone (8.3 days, p < 0.001) in 4T1 tumor models. The intratumoral IFP after RFA (45 °C) was significantly lower than baseline RFA (3.3 ± 0.8 vs. 19.2 ± 3.1 mmHg, p < 0.001), but was not measurable after RFA (70 °C). Conclusions : A two-step ablation combined with chemotherapeutic liposomes can achieve better survival benefit compared to traditional RFA in animal models.

Biodegradable polymer clips as multidimensional soft tissue biopsy markers were developed with better biocompatibility and imaging features. Unlike the commercially available metallic biopsy markers, the developed polymer clips are temporary implants with similar efficacies as metal markers in imaging and detection and get absorbed within the body with time. Herein, we evaluate the degradation rate of three resorbable polymer-based marker compounds in an in vivo murine model. Three polymers, abbreviated as Polymer A (PLGA poly(lactic- co -glycolic acid)50:50), Polymer B (PLGA (poly(lactic- co -glycolic acid)) 75:25), and Polymer C (polycaprolactone (PCL)), mixed with 20% lipiodol and 0.2% iron oxide and a control polymer were implanted into nine mice, followed by CT and MRI imaging. Images were evaluated for conspicuity. Specimens were examined for tissue analysis of iodine and iron contents. Significant differences in polymer resorption and visualization on CT were noted, particularly at 8 weeks ( p < 0.027). Polymers A, B, and C were visible by CT at 4, 6, and 8 weeks, respectively. All marker locations were detected on MRI (T1 and SWI) after 24 weeks, with tattooing of the surrounding soft tissue by iron deposits. CT and MR visible polymer markers can be constructed to possess variable resorption, with stability ranging between 4 and 14 weeks post placement, making this approach suitable for distinct clinical scenarios with varying time points.

Background: Over the last two decades, augmented reality (AR) has been used as a visualization tool in many medical fields in order to increase precision, limit the radiation dose, and decrease the variability among operators. Here, we report the first in vivo study of a novel AR system for the guidance of percutaneous interventional oncology procedures. Methods: Eight patients with 15 liver tumors (0.7−3.0 cm, mean 1.56 + 0.55) underwent percutaneous thermal ablations using AR guidance (i.e., the Endosight system). Prior to the intervention, the patients were evaluated with US and CT. The targeted nodules were segmented and three-dimensionally (3D) reconstructed from CT images, and the probe trajectory to the target was defined. The procedures were guided solely by AR, with the position of the probe tip was subsequently confirmed by conventional imaging. The primary endpoints were the targeting accuracy, the system setup time, and targeting time (i.e., from the target visualization to the correct needle insertion). The technical success was also evaluated and validated by co-registration software. Upon completion, the operators were assessed for cybersickness or other symptoms related to the use of AR. Results: Rapid system setup and procedural targeting times were noted (mean 14.3 min; 12.0−17.2 min; 4.3 min, 3.2−5.7 min, mean, respectively). The high targeting accuracy (3.4 mm; 2.6−4.2 mm, mean) was accompanied by technical success in all 15 lesions (i.e., the complete ablation of the tumor and 13/15 lesions with a >90% 5-mm periablational margin). No intra/periprocedural complications or operator cybersickness were observed. Conclusions: AR guidance is highly accurate, and allows for the confident performance of percutaneous thermal ablations.

Purpose: To determine whether specific ultrasonographic features can predict failure of conservative treatment of acute appendicitis., Methods: A 2-year retrospective study was conducted on children admitted with acute appendicitis. Those with uncomplicated appendicitis diagnosed solely by ultrasound, and treated conservatively, were followed 18-24 m to assess treatment outcome. Management was considered successful if recurrent acute appendicitis was not observed during follow-up. Appendix diameter, wall thickness, presence of mucosal ulceration, hyperechogenic fat, free fluid, and lymph nodes were evaluated as potential discriminatory ultrasonographic predictors. T-tests, chi-square, sensitivity, specificity, and odds ratios were calculated., Results: Out of 556 consecutive patients that were admitted with acute appendicitis, 180 (32%) managed conservatively. One hundred eleven (62%) imaged by US only. Ninety-two out of 111 (83%) were followed 18-24 m to assess treatment outcome, and 19/111 (17%) were lost to follow-up. Conservative management was successful in 72/92 (78.2%), with treatment failure in 20/92 (21.8%) (5/92 (5.4%) with recurrent acute appendicitis and 15/92 (16.3%) underwent appendectomy). Of the ultrasonographic features studied, mucosal ulceration demonstrated statistically significant predictive value. Fifteen out of 20 (75%) treatment failures had mucosal ulceration, compared to 21/72 (29.2%) of the patients with successful treatment (p < 0.001). This yielded a positive odds ratio of 7.3 (2.3-22.6, 95% CI), 70.8% (58.9-80.9, 95% CI) specificity, and 75% (50.9-91.3, 95% CI) sensitivity. Positive predictive value was 41.6% (31.5-52.5, 95% CI) while intact mucosa had negative predictive value of 91% (82.4-95.6, 95% CI) for conservative management success., Conclusion: The presence or absence of appendiceal mucosal ulceration at ultrasound can predict conservative management outcome in the setting of acute appendicitis, potentially improving pediatric patient selection for conservative management., (© 2021. American Society of Emergency Radiology.)