• Hepatocellular carcinoma
• hepatectomy
• iodine-125 seeds
• radiofrequency ablation
• transarterial chemoembolization

• Humans
• Male
• Female
• Carcinoma, Hepatocellular/therapy
• Carcinoma, Hepatocellular/mortality
• Carcinoma, Hepatocellular/surgery
• Liver Neoplasms/therapy
• Liver Neoplasms/mortality
• Liver Neoplasms/surgery
• Liver Neoplasms/pathology
• Middle Aged
• Iodine Radioisotopes/administration & dosage
• Iodine Radioisotopes/therapeutic use
• Chemoembolization, Therapeutic/methods
• Retrospective Studies
• Hepatectomy/methods
• Neoplasm Recurrence, Local/therapy
• Radiofrequency Ablation/methods
• Aged
• Adult
• Combined Modality Therapy/methods
• Treatment Outcome

• Humans
• Ablation Techniques/methods
• Surgery, Computer-Assisted/methods
• Bone Neoplasms/surgery

• gradual temperature rise
• radiofrequency ablation
• temperature-controlled
• turn-up time

• Project Number: KMDF_PR_20200901_0059, 1711194236 Korea Medical Device Development Fund grant funded by the Korean government (Ministry of Science and Information and Communication Technology; Ministry of Trade, Industry, and Energy; Ministry of Health and Welfare; Ministry of Food and Drug Safety)

• colorectal cancer liver metastases
• combination therapies
• hepatocellular carcinoma
• incomplete radiofrequency ablation
• tumor microenvironment

• National Natural Science Foundation of China
• Natural Science Foundation of Guangdong Province
• Southern Medical University

• Computed tomography
• Linear endoscopic ultrasound
• Lung cancer
• Magnetic resonance imaging
• Mediastinal examination

• Humans
• Endosonography/methods
• Endosonography/trends
• Mediastinum/diagnostic imaging
• Neoplasm Staging
• Mediastinal Neoplasms/diagnostic imaging
• Mediastinal Neoplasms/pathology
• Lung Neoplasms/diagnostic imaging
• Lung Neoplasms/pathology
• Mediastinal Diseases/diagnostic imaging
• Esophageal Neoplasms/diagnostic imaging
• Esophageal Neoplasms/pathology
• Lymphadenopathy/diagnostic imaging
• Lymphadenopathy/pathology
• Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods
• Tomography, X-Ray Computed/methods
• Tomography, X-Ray Computed/trends

• ablative therapy
• abscopal effect
• immunotherapy
• locoregional therapy
• tissue ablation
• tumor necrosis

• Humans
• Animals
• Ablation Techniques/methods

• R01HL137193 NHLBI NIH HHS
• R01 CA257558 NCI NIH HHS
• R01 HL140951 NHLBI NIH HHS
• R01 DK130566 NIDDK NIH HHS
• Clinician Investigator Award Mayo Clinic
• R01CA257558 NCI NIH HHS
• R01DK130566 NIDDK NIH HHS
• R01 HL165176 NHLBI NIH HHS
• R01 HL137193 NHLBI NIH HHS

• Hepatocellular carcinoma
• Iodine-125 seeds
• Radiofrequency ablation
• Recurrence

• Humans
• Liver Neoplasms/surgery
• Liver Neoplasms/radiotherapy
• Liver Neoplasms/mortality
• Liver Neoplasms/pathology
• Carcinoma, Hepatocellular/surgery
• Carcinoma, Hepatocellular/radiotherapy
• Carcinoma, Hepatocellular/mortality
• Carcinoma, Hepatocellular/pathology
• Iodine Radioisotopes/therapeutic use
• Iodine Radioisotopes/administration & dosage
• Hepatectomy/methods
• Male
• Female
• Middle Aged
• Neoplasm Recurrence, Local
• Retrospective Studies
• Radiofrequency Ablation/methods
• Radiofrequency Ablation/adverse effects
• Aged
• Adult
• Combined Modality Therapy
• Treatment Outcome
• Tomography, X-Ray Computed

• Warthin’s tumors
• minimally invasive
• parotid gland
• radiofrequency ablation

• Hepatocellular carcinoma
• Prognosis
• Radiofrequency ablation
• Transformer

• Humans
• Carcinoma, Hepatocellular/pathology
• Liver Neoplasms/pathology
• Catheter Ablation/methods
• Neoplasm Recurrence, Local/surgery
• Prognosis
• Radiofrequency Ablation
• Retrospective Studies
• Treatment Outcome

• 23HC2001 Ministry of Health, Labour and Welfare
• The University of Tokyo

• Humans
• Catheter Ablation/methods
• Liver/pathology
• Liver/surgery
• Radiofrequency Ablation/methods
• Neoplasms/radiotherapy
• Neoplasms/surgery

• ablation
• electroporation
• histotripsy
• interventional radiology
• liver cancer
• percutaneous alcohol ablation

• Animals
• Mice
• Picibanil/pharmacology
• Liver Neoplasms/drug therapy
• Carcinoma, Hepatocellular/drug therapy
• Hydrogels/pharmacology
• Hydrogels/chemistry
• CD8-Positive T-Lymphocytes
• Doxorubicin/pharmacology
• Doxorubicin/chemistry
• Cytokines
• Radiofrequency Ablation

• 82072041 National Natural Science Foundation of China
• 2023AFA107 the Outstanding Youth Foundation of Hubei Province, China

• heterogeneity
• microenvironment
• pancreatic cancer
• personalized therapy
• single-cell sequencing

• Clinical
• Diagnostics
• Endogenous
• Image-guided
• Interventions
• Photoacoustics
• Spectroscopy
• Theranostics
• Ultrasound

• mathematic simulation
• radiofrequency ablation
• radiofrequency hyperthermia

• R01 EB028095 NIBIB NIH HHS
• R01EB028095 NIH HHS

• Intervention
• Liver
• Segmentation
• Surgery
• Tumor

• Carcinoma, Hepatocellular/diagnostic imaging
• Carcinoma, Hepatocellular/surgery
• Humans
• Liver Neoplasms/diagnostic imaging
• Liver Neoplasms/surgery
• Magnetic Resonance Imaging
• Tomography, X-Ray Computed

Although immune checkpoint inhibitors (ICIs) have achieved great progression in cancer treatment, the efficacy of ICI monotherapy is still limited. Meanwhile, the negative efficacy of thermal ablation for liver metastases is the high rate of local tumor progression. Since thermal ablation-induced inflammation and increases in tumor antigens have been suggested to promote the cancer-immunity cycle, thermal ablation and ICI can boost the immune response against cancer cells as one of the positive synergy effects. The findings of preclinical and clinical research have provided supportive evidence for the combination of ICIs with thermal ablation reversing T-cell exhaustion and demonstrating synergy. However, the clinical feasibility of immune response activation by combination therapy with ICI monotherapy and thermal ablation appears to be limited, it may be not very common phenomena.

Cancer immunotherapy, which reactivates the weakened immune cells of cancer patients, has achieved great success, and several immune checkpoint inhibitors (ICIs) are now available in clinical practice. Despite promising clinical outcomes, favorable responses are only observed in a fraction of patients, and resistance mechanisms, including the absence of tumor antigens, have been reported. Thermal ablation involves the induction of irreversible damage to cancer cells by localized heat and may result in the release of tumor antigens. The combination of immunotherapy and thermal ablation is an emerging therapeutic option with enhanced efficacy. Since thermal ablation-induced inflammation and increases in tumor antigens have been suggested to promote the cancer-immunity cycle, the combination of immuno-oncology (IO) therapy and thermal ablation may be mutually beneficial. In preclinical and clinical studies, the combination of ICI and thermal ablation significantly inhibited tumor growth, and synergistic antitumor effects appeared to prolong the survival of patients with secondary liver cancer. However, evidence for the efficacy of ICI monotherapy combined with thermal ablation is currently insufficient. Therefore, the clinical feasibility of immune response activation by ICI monotherapy combined with thermal ablation may be limited, and thermal ablation may be more compatible with dual ICIs (the IO–IO combination) to induce strong immune responses.

• immune checkpoint inhibitor
• immuno-oncology
• information dissemination
• liver metastasis
• thermal ablation
• tumor antigen

To develop a new interventional oncology technique using indocyanine green (ICG)-based interventional optical imaging (OI) to monitor the synergistic effect of radiofrequency hyperthermia (RFH)-enhanced oncolytic immunotherapy.

This study included (1) optimization of ICG dose and detection time-window for intracellular uptake by VX2 tumor cells; (2) in-vitro confirmation of capability of using ICG-based OI to assess efficacy of RFH-enhanced oncolytic therapy (LTX-401) for VX2 cells; and (3) in-vivo validation of the interventional OI-monitored, intratumoral RFH-enhanced oncolytic immunotherapy using rabbit models with orthotopic liver VX2 tumors. Both in-vitro and in-vivo experiments were divided into four study groups (n=6/group) with different treatments: (1) combination therapy of RFH+LTX-401; (2) RFH alone at 42°C for 30 min; (3) oncolytic therapy with LTX-401; and (4) control with saline. For in-vivo validation, orthotopic hepatic VX2 tumors were treated using a new multi-functional perfusion-thermal radiofrequency ablation electrode, which enabled simultaneous delivery of both LTX-401 and RFH within the tumor and at the tumor margins.

In in-vitro experiments, taking up of ICG by VX2 cells was linearly increased from 0 μg/mL to 100 μg/mL, while ICG-signal intensity (SI) reached the peak at 24 hours. MTS assay and apoptosis analysis demonstrated the lowest cell viability and highest apoptosis in combination therapy, compared to three monotherapies (P<0.005). In in-vivo experiments, ultrasound imaging detected the smallest relative tumor volume for the combination therapy, compared to other monotherapies (P<0.005). In both in-vitro and in-vivo experiments, ICG-based interventional optical imaging detected a significantly decreased SI in combination therapy (P<0.005), which was confirmed by the “gold standard” optical/X-ray imaging (P<0.05). Pathologic/laboratory examinations further confirmed the significantly decreased cell proliferation with Ki-67 staining, significantly increased apoptotic index with TUNEL assay, and significantly increased quantities of CD8 and CD80 positive cells with immunostaining in the combination therapy group, compared to other three control groups (P<0.005).

We present a new interventional oncology technique, interventional optical imaging-monitored RFH-enhanced oncolytic immunotherapy, which may open new avenues to effectively manage those patients with larger, irregular and unresectable malignancies, not only in liver but also the possibility in other organs.

• R01 EB028095 NIBIB NIH HHS
• National Institutes of Health

Hepatocellular carcinoma (HCC) is one of the most deadly and frequent cancers worldwide, although great advancement in the treatment of this malignancy have been made within the past few decades. It continues to be a major health issue due to an increasing incidence and a poor prognosis. The majority of patients have their HCC diagnosed at an intermediate or advanced stage in theUSA or China. Curative therapy such as surgical resection or liver transplantation is not considered anoption of treatment at these stages.

Transarterial chemoembolization (TACE), the most widely used locoregional therapeutic approach, used to be the mainstay of treatment for cases with unresectable cancer entities. However, for those patients with hypovascular tumors or impaired liver function reserve, TACE is a suboptimal treatment option. For example, embolization does not result in complete coverage of a hypovascular tumor, and may rather promotes postoperative tumor recurrence, or leave residual tumor, in these TACE-resistance patients. In addition, TACE carries a higher risk of hepatic decompensation in patients with poor liver function or reserve.

Non-vascular interventional locoregional therapies for HCC include radiofrequency ablation (RFA), microwave ablation (MWA), high-intensity focused ultrasound (HIFU), laser-induced thermotherapy (LITT), cryosurgical ablation (CSA), irreversible Electroporation (IRE), percutaneous ethanol injection (PEI), and brachytherapy. Recent advancements in these techniques have significantly improved the treatment efficacy of HCC and expanded the population of patients who qualify for treatment. This review embraces the current status of imaging-guided locoregional non-intravascular interventional treatments for HCCs, with a primary focus on the clinical evaluation and assessment of the efficacy of combined therapies using these interventional techniques.

• Backflow
• Joule heating
• Poiseuille
• RFA
• Saline infusion

• Catheter Ablation
• Electrodes
• Liver/surgery
• Porosity
• Radiofrequency Ablation

• Hepatocellular carcinoma
• Radiofrequency ablation
• Recurrence
• Stereotactic body radiotherapy
• Survival
• Tumor response

• Aged
• Aged, 80 and over
• Carcinoma, Hepatocellular/diagnostic imaging
• Carcinoma, Hepatocellular/mortality
• Carcinoma, Hepatocellular/pathology
• Carcinoma, Hepatocellular/therapy
• Combined Modality Therapy/adverse effects
• Combined Modality Therapy/methods
• Feasibility Studies
• Female
• Humans
• Liver Neoplasms/diagnostic imaging
• Liver Neoplasms/mortality
• Liver Neoplasms/pathology
• Liver Neoplasms/therapy
• Male
• Middle Aged
• Neoplasm Staging/methods
• Neoplasms, Multiple Primary/mortality
• Neoplasms, Multiple Primary/pathology
• Neoplasms, Multiple Primary/therapy
• Pilot Projects
• Progression-Free Survival
• Radiofrequency Ablation/adverse effects
• Radiofrequency Ablation/methods
• Radiofrequency Ablation/statistics & numerical data
• Radiosurgery/adverse effects
• Radiosurgery/methods
• Radiosurgery/statistics & numerical data
• Retrospective Studies
• Survival Rate
• Treatment Outcome

To present a novel methodical approach to compare visibility of percutaneous needles in ultrasound images.

A motor‐driven rotation platform was used to gradually change the needle angle while capturing image data. Data analysis was automated using block‐matching‐based registration, with a tracking and refinement step. Every 25 frames, a Hough transform was used to improve needle alignments after large rotations. The method was demonstrated by comparing three commercial needles (14G radiofrequency ablation, RFA; 18G Trocar; 22G Chiba) and six prototype needles with different sizes, materials, and surface conditions (polished, sand‐blasted, and kerfed), within polyvinyl alcohol phantom tissue and ex vivo bovine liver models. For each needle and angle, a contrast‐to‐noise ratio (CNR) was determined to quantify visibility. CNR values are presented as a function of needle type and insertion angle. In addition, the normalized area under the (CNR‐angle) curve was used as a summary metric to compare needles.

In phantom tissue, the first kerfed needle design had the largest normalized area of visibility and the polished 1 mm diameter stainless steel needle the smallest (0.704 ± 0.199 vs. 0.154 ± 0.027, p < 0.01). In the ex vivo model, the second kerfed needle design had the largest normalized area of visibility, and the sand‐blasted stainless steel needle the smallest (0.470 ± 0.190 vs. 0.127 ± 0.047, p < 0.001). As expected, the analysis showed needle visibility peaks at orthogonal insertion angles. For acute or obtuse angles, needle visibility was similar or reduced. Overall, the variability in needle visibility was considerably higher in livers.

The best overall visibility was found with kerfed needles and the commercial RFA needle. The presented methodical approach to quantify ultrasound visibility allows comparisons of (echogenic) needles, as well as other technological innovations aiming to improve ultrasound visibility of percutaneous needles, such as coatings, material treatments, and beam steering approaches.

• Hough transform
• block-matching-based registration
• bovine liver model
• contrast-to-noise ratio
• experimental methods
• needle interventions
• polyvinyl alcohol
• ultrasound
• visibility

• hepatic VX2 tumor
• indocyanine green
• interventional optical imaging
• radiofrequency ablation
• residual tumor

Given the metachronous and multifocal occurrence of hepatocellular carcinoma (HCC) and colorectal cancer metastases in the liver (CRLM), this study aimed to compare intrahepatic progression patterns after computed tomography (CT)-guided high dose-rate brachytherapy.

This retrospective analysis included 164 patients (114 HCC, 50 CRLM) treated with brachytherapy between January 2016 and January 2018. Patients received multiparametric magnetic resonance imaging (MRI) before, and about 8 weeks after brachytherapy, then every 3 months for the first, and every 6 months for the following years, until progression or death. MRI scans were assessed for local or distant intrahepatic tumor progression according to RECIST 1.1 and electronic medical records were reviewed prior to therapy. The primary endpoint was progression-free survival (PFS). Specifically, local and distant intra-hepatic PFS were assessed to determine differences between the intrahepatic progression patterns of HCC and CRLM. Secondary endpoints included the identification of predictors of PFS, time to progression (TTP), and overall survival (OS). Statistics included Kaplan–Meier analysis and univariate and multivariate Cox regression modeling.

PFS was longer in HCC [11.30 (1.33–35.37) months] than in CRLM patients [8.03 (0.73–19.80) months, p = 0.048], respectively. Specifically, local recurrence occurred later in HCC [PFS: 36.83 (1.33–40.27) months] than CRLM patients [PFS: 12.43 (0.73–21.90) months, p = 0.001]. In contrast, distant intrahepatic progression occurred earlier in HCC [PFS: 13.50 (1.33–27.80) months] than in CRLM patients [PFS: 19.80 (1.43–19.80) months, p = 0.456] but without statistical significance. Multivariate Cox regression confirmed tumor type and patient age as independent predictors for PFS.

Brachytherapy proved to achieve better local tumor control and overall PFS in patients with unresectable HCC as compared to those with CRLM. However, distant progression preceded local recurrence in HCC. As a result, these findings may help design disease-specific surveillance strategies and personalized treatment planning that highlights the strengths of brachytherapy. They may also help elucidate the potential benefits of combinations with other loco-regional or systemic therapies.

• HCC imaging
• ablation
• brachytherapy
• local ablation therapy
• prognostic prediction
• radiation therapy

• Animals
• Cell Differentiation
• Cell Line, Tumor
• Female
• Hepatocytes/metabolism
• Humans
• In Vitro Techniques
• Indocyanine Green/pharmacology
• Liver/metabolism
• Liver Neoplasms/diagnostic imaging
• Neoplasm, Residual/drug therapy
• Optical Imaging/methods
• Rabbits

• R01 EB028095 NIBIB NIH HHS

• chemoprevention
• diet
• flavonoids
• hepatocellular carcinoma
• kaempferol
• quercetin
• resveratrol

• Carcinoma, Hepatocellular/drug therapy
• Carcinoma, Hepatocellular/prevention & control
• Chemoprevention
• Flavonoids/therapeutic use
• Humans
• Liver Neoplasms/drug therapy
• Liver Neoplasms/prevention & control
• Resveratrol

Unresectable liver tumors are commonly treated with percutaneous radiofrequency ablation (RFA). However, this technique is associated with high recurrence rates due to incomplete tumor ablation. Accurate image guidance of the RFA procedure contributes to successful ablation, but currently used imaging modalities have shortcomings in device guidance and treatment monitoring. We explore the potential of using photoacoustic (PA) imaging combined with conventional ultrasound (US) imaging for real-time RFA guidance. To overcome the low penetration depth of light in tissue, we have developed an annular fiber probe (AFP), which can be inserted into tissue enabling interstitial illumination of tissue. The AFP is a cannula with 72 optical fibers that allows an RFA device to slide through its lumen, thereby enabling PA imaging for RFA device guidance and ablation monitoring. We show that the PA signal from interstitial illumination is not affected by absorber-to-surface depth compared to extracorporeal illumination. We also demonstrate successful imaging of the RFA electrodes, a blood vessel mimic, a tumor-mimicking phantom, and ablated liver tissue boundaries in ex vivo chicken and bovine liver samples. PA-assisted needle guidance revealed clear needle tip visualization, a notable improvement to current US needle guidance. Our probe shows potential for RFA device guidance and ablation detection, which potentially aids in real-time monitoring.

• interstitial illumination
• interventional imaging
• liver treatment
• minimally invasive procedures
• multimodal imaging
• photoacoustics
• radiofrequency ablation
• surgical tool tracking
• ultrasound imaging

• Combined treatment
• Guideline
• Hepatocellular carcinoma
• Immunotherapy
• Radiotherapy
• Stereotactic body radiotherapies

• Carcinoma, Hepatocellular/radiotherapy
• Humans
• Liver Neoplasms/radiotherapy
• Neoplasm Recurrence, Local
• Radiosurgery

• Cross-Correlation algorithm
• Hyperspectral imaging
• Liver tissue thermal Effect
• Liver tumor
• Radiofrequency thermal Ablation
• Spectral signature

• Treatment algorithms
• hepatocellular carcinoma
• individual outcomes
• patient stratification
• radiofrequency ablation

To evaluate the treatment effect of radiofrequency-induced hyperthermia (RFH) combined with intra-tumoral chemotherapy for rabbit VX2 liver tumors and explore the underlying mechanism that drives local hyperthermia-enhanced chemotherapy.

VX2 cell lines and rabbits with liver VX2 tumors were randomly allocated to four treatment groups including: (1) combination therapy of Doxorubicin (DOX) plus hyperthermia/RFH (n=6); (2) DOX only; (3) hyperthermia/RFH only (n=6); and (4) phosphate-buffered saline-treated control (n=6). Cell viability and doxorubicin uptake by VX2 tumor cells were assayed using flow cytometry and fluorescence microscopy 24 h after treatments. Western blot was used to evaluate the expression level of heat shock protein 70 (HSP70) in tumor cells and tissues. For the harvested VX2 tumors, fluorescence microscopy was used to evaluate the distribution and penetration of doxorubicin in tumor tissues and HSP70 expression was analyzed by Western blot and immunohistochemistry.

RFH enhanced the chemotherapeutic effect of doxorubicin in VX2 cells and rabbit liver VX2 tumors resulting in higher apoptosis and lower cell viability. Flowcytometry of VX2 cells showed more apoptotic cells in combination therapy of hyperthermia and DOX, compared with other three groups in-vitro experiments (45.80 ± 1.27% vs 20.66 ± 0.71%, vs 15.16 ± 0.81% and 0.62 ± 0.06%, respectively, p<0.01). The quantitative analysis by Western blot and immunohistochemistry showed increased expression of HSP70 in both VX2 tumor cells (1.28 ± 0.13 vs 0.64 ± 0.13 vs 0.83 ± 0.10 vs 0.15 ± 0.03, respectively, p<0.05) and tumors (1.47 ± 0.13 vs 0.51 ± 0.13 vs 0.74 ± 0.11 vs 0.16 ± 0.04, respectively, p <0.01). Fluorescence microscopy showed increased uptake of DOX in tumor cells in the combination therapy group.

RFH/hyperthermia enhanced the chemotherapeutic effect of DOX in VX2 tumors by promoting the uptake of DOX and the expression HSP70 in tumors.

• chemotherapy
• doxorubicin
• heat shock protein 70
• hepatic tumors
• radiofrequency hyperthermia

• hepatocellular carcinoma (HCC)
• immune response
• metastasis
• nanosecond pulsed electric fields (nsPEF)
• recurrence

• Joule heating
• Microscopic mixture model
• NaCl
• RFA
• Saline infusion

• Biliary cooling
• Biliary stricture
• Radiofrequency ablation

• Bile Ducts/diagnostic imaging
• Bile Ducts/pathology
• Biliary Tract
• Constriction, Pathologic/diagnostic imaging
• Constriction, Pathologic/etiology
• Humans
• Hypothermia, Induced
• Liver Neoplasms/pathology
• Liver Neoplasms/therapy
• Neoplasm Recurrence, Local
• Radiofrequency Ablation/adverse effects

• G1002543 Medical Research Council

• Hyperspectral imaging
• K-mean clustering algorithm
• Liver tumor
• RF thermal ablation
• Spectral diffuse reflectance

• Bonopty needle device
• Hepatocellular carcinoma
• Irreversible electroporation
• Transchondral access

• Cancer treatment
• Computational modelling
• Joule heating
• RFA
• Thermal ablation

• Animals
• Computer Simulation
• Finite Element Analysis
• Imaging, Three-Dimensional
• Liver/surgery
• Radiofrequency Ablation
• Saline Solution/administration & dosage

• Focal therapy
• clinical trials-thermal ablation
• noninvasive thermometry
• physiological effects of hyperthermia
• ultrasound

• Finite-element method (FEM)
• microwave ablation
• microwave ablation device
• tissue-mimicking phantom

• Contrast-to-noise ratio
• Echogenicity
• Experimental methods
• High-echoic range
• Needle interventions
• Polyvinyl alcohol
• Signal ratio
• Ultrasound
• Visibility

• Humans
• Needles
• Ultrasonography, Interventional/instrumentation

• Enhanced RF heating
• pre-freezing
• tissue temperature transients

• chemoembolization
• cholangiocarcinoma
• hepatocellular carcinoma
• percutaneous ablation
• radioembolization