Evaluation of a delayed liver transplantation strategy for patients with HCC receiving bridging therapy: the DELTA-HCC study.

BACKGROUND & AIMS: To maximize utility and prevent premature liver transplantation (LT), a delayed LT strategy (DS) was adopted in France in 2015 in patients listed for any single HCC treated with resection or thermal ablation during the waiting phase. The DS involves postponing LT until recurrence. The purpose of this study was to evaluate the DS to make sure that it did not hamper pre- and post-LT outcomes. METHODS: Patients listed for HCC in France between 2015 and 2018 were studied. After data extraction from the national LT database, 2,025 patients were identified and classified according to six groups: single tumor entering DS, single tumor not entering DS, multiple tumors, no curative treatment, untreatable HCC or T1 tumors. Kaplan-Meier estimates of the 18-month risk of dropout for death, too sick to be transplanted or tumor progression before LT, 5-year post-LT HCC recurrence and post-LT survival rates were compared. RESULTS: Median waiting-time in the DS group was 910 days. Pre-LT dropout probability was significantly lower in the DS group compared to other groups (13% vs. 19%, p = 0.0043) and significantly higher in the T1 group (25.4%, p = 0.05). Post-LT HCC recurrence rate in the multiple nodules group was significantly higher (19.6%, p = 0.019), while 5-year post-LT survival did not differ among groups and was 74% in the DS group (p = 0.22). CONCLUSION: The DELTA-HCC study shows that DS does not negatively impact either pre- nor post-LT patient outcomes, and has the potential to allow for redistribution of organs to patients in more urgent need of LT. It can reasonably be proposed and pursued. The unexpectedly high risk of dropout in T1 patients seems related to the MELD-based offering rules underserving this subgroup. IMPACTS AND IMPLICATIONS: To maximize utility and prevent premature liver transplantation (LT), a delayed LT strategy was adopted in France in 2015. It involves postponing LT until recurrence in patients listed for any single HCC curatively treated by surgical resection or thermal ablation. The DELTA-HCC study was conducted to evaluate this nationwide strategy. It shows in a European LT program that delayed strategy does not negatively impact pre- nor post-LT patient outcomes and is relevant to up to 20% of LT candidates; thus, it could potentially enable the redistribution of organs to patients in more urgent need of LT. Such a delayed strategy can reasonably be pursued and extended to other LT programs. Of note, an unexpectedly high risk of dropout in T1 patients, seemingly related to MELD-based offering rules which underserve these patients, calls for further scrutinization and revision of allocation rules in this subgroup.

Thermal Ablation Versus Partial Nephrectomy for cT1 Renal Mass in a Solitary Kidney: A Matched Cohort Comparative Analysis.

BACKGROUND: Nephron-sparing approaches are preferred for renal mass in a solitary kidney (RMSK), with partial nephrectomy (PN) generally prioritized. Thermal ablation (TA) also is an option for small renal masses in this setting; however, comparative functional/survival outcomes are not well-defined. METHODS: A retrospective study of 504 patients (1975-2022) with cT1 RMSK managed with PN (n = 409)/TA (n = 95) with necessary data for analysis was performed. Propensity score was used for matching patients, including age, preoperative glomerular filtration rate (GFR), tumor diameter, R.E.N.A.L. ((R)adius (tumor size as maximal diameter), (E)xophytic/endophytic properties of tumor, (N)earness of tumor deepest portion to collecting system or sinus, (A)nterior (a)/posterior (p) descriptor, and (L)ocation relative to polar lines), and comorbidities. Functional outcomes were compared, and Kaplan-Meier was used to analyze survival. RESULTS: The matched cohort included 132 patients (TA = 66/PN = 66), with median tumor diameter of 2.4 cm, R.E.N.A.L. of 6, and preoperative GFR of 52 ml/min/1.73 m2. Acute kidney injury occurred in 11%/61% in the TA/PN cohorts, respectively (p < 0.01). After recovery, median GFR preserved was 89%/83% for TA/PN, respectively (p = 0.02), and 5-year dialysis-free survival was 96% in both cohorts. Median follow-up was 53 months. Five-year recurrence-free survival (RFS) was 62%/86% in the TA/PN cohorts, respectively (p < 0.01). Five-year local recurrence (LR)-free survival was 74%/95% in the TA/PN cohorts, respectively (p < 0.01). Five-year cancer-specific survival (CSS) was 96%/98% in the TA/PN cohorts, respectively (p = 0.7). Local recurrence was observed in nine of 36 (25%) and five of 30 (17%) patients managed with laparoscopic versus percutaneous TA, respectively. For TA with LR (n = 14), nine patients presented with multifocality and/or cT1b tumors. Twelve LR were managed with salvage TA, and seven remained cancer-free, while five developed systemic recurrence, three with concomitant LR. CONCLUSIONS: Functional outcomes for TA for RMSK were improved compared with PN. Local recurrence was more common after TA and often was associated with the laparoscopic approach, multifocality, and large tumor size. Improved patient selection and greater experience with TA should improve outcomes. Salvage of LR was not always possible. Partial nephrectomy remains the reference standard for RMSK.

Integrated omics characterization reveals reduced cancer indicators and elevated inflammatory factors after thermal ablation in non-small cell lung cancer patients.

BACKGROUND: Thermal ablation is a minimally invasive treatment for non-small cell lung cancer (NSCLC). Aside from causing an immediate direct tumour cell injury, the effects of thermal ablation on the internal microenvironment are unknown. This study aimed to investigate the effects of thermal ablation on the plasma internal environment in patients with NSCLC. METHODS: 128 plasma samples were collected from 48 NSCLC (pre [LC] and after thermal ablation [LC-T]) patients and 32 healthy controls (HCs). Olink proteomics and metabolomics were utilized to construct an integrated landscape of the cancer-related immune and inflammatory responses after ablation. RESULTS: Compared with HCs, LC patients exhibited 58 differentially expressed proteins (DEPs) and 479 differentially expressed metabolites (DEMs), which might participate in tumour progression and metastasis. Moreover, 75 DEPs were identified among the HC, LC, and LC-T groups. Forty-eight highly expressed DEPs (eg, programmed death-ligand 1 [PD-L1]) in the LC group were found to be downregulated after thermal ablation. These DEPs had significant impacts on pathways such as angiogenesis, immune checkpoint blockade, and pro-tumour chemotaxis. Metabolites involved in tumour cell survival were associated with these proteins at the expression and functional levels. In contrast, 19 elevated proteins (eg, interleukin [IL]-6) were identified after thermal ablation. These proteins were mainly associated with inflammatory response pathways (NF-κB signalling and tumour necrosis factor signalling) and immune cell activation. CONCLUSIONS: Thermal ablation-induced changes in the host plasma microenvironment contribute to anti-tumour immunity in NSCLC, offering new insights into tumour ablation combined with immunotherapy. Trial registration This study was registered on the Chinese Clinical Trial Registry ( https://www.chictr.org.cn/index.html ). ID: ChiCTR2300076517. Registration Date: 2023-10-11.

Thyroid ultrasound and its ancillary techniques.

Ultrasound (US) of the thyroid has been used as a diagnostic tool since the late 1960s. US is the most important imaging tool for diagnosing thyroid disease. In the majority of cases a correct diagnosis can already be made in synopsis of the sonographic together with clinical findings and basal thyroid hormone parameters. However, the characterization of thyroid nodules by US remains challenging. The introduction of Thyroid Imaging Reporting and Data Systems (TIRADSs) has improved diagnostic accuracy of thyroid cancer significantly. Newer techniques such as elastography, superb microvascular imaging (SMI), contrast enhanced ultrasound (CEUS) and multiparametric ultrasound (MPUS) expand diagnostic options and tools further. In addition, the use of artificial intelligence (AI) is a promising tool to improve and simplify diagnostics of thyroid nodules and there is evidence that AI can exceed the performance of humans. Combining different US techniques with the introduction of new software, the use of AI, FNB as well as molecular markers might pave the way for a completely new area of diagnostic accuracy in thyroid disease. Finally, interventional ultrasound using US-guided thermal ablation (TA) procedures are increasingly proposed as therapy options for benign as well as malignant thyroid diseases.

A randomised controlled trial of Standard Of Care versus RadioAblaTion in Early Stage HepatoCellular Carcinoma (SOCRATES HCC).

BACKGROUND: Therapeutic options for early-stage hepatocellular carcinoma (HCC) in individual patients can be limited by tumor and location, liver dysfunction and comorbidities. Many patients with early-stage HCC do not receive curative-intent therapies. Stereotactic ablative body radiotherapy (SABR) has emerged as an effective, non-invasive HCC treatment option, however, randomized evidence for SABR in the first line setting is lacking. METHODS: Trans-Tasman Radiation Oncology Group (TROG) 21.07 SOCRATES-HCC is a phase II, prospective, randomised trial comparing SABR to other current standard of care therapies for patients with a solitary HCC ≤ 8 cm, ineligible for surgical resection or transplantation. The study is divided into 2 cohorts. Cohort 1 will compromise 118 patients with tumors ≤ 3 cm eligible for thermal ablation randomly assigned (1:1 ratio) to thermal ablation or SABR. Cohort 2 will comprise 100 patients with tumors > 3 cm up to 8 cm in size, or tumors ≤ 3 cm ineligible for thermal ablation, randomly assigned (1:1 ratio) to SABR or best other standard of care therapy including transarterial therapies. The primary objective is to determine whether SABR results in superior freedom from local progression (FFLP) at 2 years compared to thermal ablation in cohort 1 and compared to best standard of care therapy in cohort 2. Secondary endpoints include progression free survival, overall survival, adverse events, patient reported outcomes and health economic analyses. DISCUSSION: The SOCRATES-HCC study will provide the first randomized, multicentre evaluation of the efficacy, safety and cost effectiveness of SABR versus other standard of care therapies in the first line treatment of unresectable, early-stage HCC. It is a broad, multicentre collaboration between hepatology, interventional radiology and radiation oncology groups around Australia, coordinated by TROG Cancer Research. TRIAL REGISTRATION: anzctr.org.au, ACTRN12621001444875, registered 21 October 2021.

Salvage stereotactic ablative body radiotherapy after thermal ablation of primary kidney cancer.

OBJECTIVE: To evaluate the effectiveness and safety of salvage stereotactic ablative body radiotherapy (SABR) for recurrent renal cell carcinoma (RCC) after thermal ablation (TA). MATERIALS AND METHODS: This study was a multi-institutional retrospective analysis of patients with recurrent RCC following TA who received SABR between 2016 and 2020. The primary study outcome was freedom from local failure, evaluated radiographically based on Response Evaluation Criteria in Solid Tumours (RECIST) v1.1. Distant failure, cancer-specific survival (CSS), overall survival (OS), treatment-related toxicity and renal function changes following SABR were the secondary outcomes. The Kaplan-Meier method was used to estimate freedom from local and distant failure, CSS and OS. RESULTS: Seventeen patients with 18 biopsy-confirmed RCCs were included, with a median (interquartile range [IQR]) age at time of SABR of 75.2 (72.6-68.7) years, a median (IQR) tumour size of 3.5 (1.9-4.1) cm and follow-up (reverse Kaplan-Meier method) of 3.36 (95% confidence interval [CI] 1.6-4.1) years. Six of the 17 patients had a solitary kidney. Five patients had failed repeat TA prior to SABR. The median (IQR) time from TA procedure to SABR was 3.03 (1.5-5.1) years. No patient experienced local progression, with a local control rate of 100%. Four patients, two with baseline metastatic disease, experienced distant progression. The distant progression-free survival, CSS and OS at 3 years were 72.1% (95% CI 51.9%-100%), 92.3% (95% CI 78.9%-100%) and 82.1% (95% CI 62.1%-100%), respectively. The median (IQR) glomerular filtration rate before SABR was 58 (40-71) mL/min, and at last follow-up, it was 48 (33-57) mL/min. No patient experienced grade 3+ toxicity or went on to develop end-stage renal disease. CONCLUSION: The results showed that SABR appears to be an effective and safe salvage strategy in patients with recurrent RCC following TA.

Complications of ultrasound-guided thermal ablation of thyroid nodules and associated risk factors: an experience from 9667 cases.

OBJECTIVES: To evaluate the safety of ultrasound-guided thermal ablation (UGTA) for thyroid nodules (TNs) by analysing complications and related risks. MATERIALS AND METHODS: This retrospective, single-centre study reviewed patients who underwent UGTA (microwave or radiofrequency ablation) between January 2018 and March 2023. The incidence of complications was recorded and assessed during and immediately after ablation,1-3 h later, and at 1 month, 3 months, and 6 months. Univariate and multivariate analyses were performed to identify risk factors for hoarseness and haemorrhagic complications. RESULTS: We reviewed 9667 cases in this study. Overall, 4494 (46.49%) cases underwent microwave ablation, while 5173 (53.51%) cases underwent radiofrequency ablation. The overall complication rate was 4.43%. The incidence of major complications was 1.94% (haemorrhage, 1.32%; hoarseness, 0.54%; and symptomatic aseptic necrosis, 0.08%). The incidence of minor complications was 2.45%. A large nodule volume, radiofrequency ablation, hyper-enhancing nodules, benign nodules, higher preoperative blood pressure, hyperthyroidism, and higher ablation power were independent risk factors for haemorrhage. Dorsal nodules and a higher ablation power were independent risk factors for hoarseness. All complications were resolved. CONCLUSION: This study suggests that UGTA is a safe treatment for TNs. Several risk factors for haemorrhage and hoarseness should be considered before performing UGTA. Different ablation modalities should be considered for patients with different conditions. CLINICAL RELEVANCE STATEMENT: Thermal ablation may be a safe treatment for eligible patients with TNs. KEY POINTS: We analysed the complications and risk factors associated with UGTA in 9667 cases. The complication rate was 4.43%; 1.94% were major complications. Risk factors of haemorrhage and hoarseness should be considered. UGTA was a safe method for the treatment of TNs.

Local recurrence rates after resection of large colorectal serrated lesions with or without margin thermal ablation.

INTRODUCTION: Serrated lesions (SLs) including traditional serrated adenomas (TSA), large hyperplastic polyps (HP) and sessile serrated lesions (SSLs) are associated with high incomplete resection rates. Margin ablation combined with EMR (EMR-T) has become routine to reduce local recurrence while cold snare polypectomy (CSP) is becoming recognized as equally effective for large SLs. Our aim was to evaluate local recurrence rates (LRR) and the use of margin ablation in preventing recurrence in a retrospective cohort study. METHODS: Patients undergoing resection of ≥15 mm colorectal SLs from 2010-2022 were identified through a pathology database and electronic medical records search. Hereditary CRC syndromes, first follow-up > 18 months or no follow-up, surgical resection were excluded. Primary outcome was LRRs (either histologic or visual) during the first 18-month follow-up. Secondary outcomes were LRRs according to size, and resection technique. RESULTS: 191 polyps in 170 patients were resected (59.8% women; mean age, 65 years). The mean size of polyps was 22.4 mm, with 107 (56.0%) ≥20 mm. 99 polyps were resected with EMR, 39 with EMR-T, and 26 with CSP. Mean first surveillance was 8.2 mo. Overall LRR was 18.8% (36/191) (16.8% for ≥20 mm, 17.9% for ≥30 mm). LRR was significantly lower after EMR-T when compared with EMR (5.1% vs. 23.2%; p = 0.013) or CSP (5.1% vs. 23.1%; p = 0.031). There was no difference in LRR between EMR without margin ablation and CSP (p = 0.987). CONCLUSION: The local recurrence rate for SLs ≥15 mm is high with 18.8% overall recurrence. EMR with thermal ablation of the margins is superior to both no ablation and CSP in reducing LRRs.

Radiofrequency ablation of hepatocellular carcinoma guided by real-time physics-based ablation simulation: a prospective study.

OBJECTIVES: To assess the safety and efficacy of radiofrequency ablation (RFA) guidance software that incorporated patient-specific physics-based simulation of each ablation volume. MATERIALS AND METHODS: Patients referred for curative ablation of hepatocellular carcinoma (HCC) of 2-5 cm diameter were prospectively enrolled. RFA was performed under general anesthesia. Procedure planning and intraprocedural modifications were guided by computer simulation of each ablation. The segmented target (tumor with 5 mm margin) was registered to and superimposed on subsequent 3D multiplanar images. The applied RF energy was used to calculate a simulated ablation volume which was displayed relative to the electrode and segmented target, to depict any untreated target tissue. After each additional ablation, the software updated the accumulated simulated ablation volume in relation to the target. The primary endpoints were technical efficacy and rate of local tumor progression (LTP). RESULTS: Sixty-eight tumors were ablated during 57 procedures in 52 patients (68.3 ± 9.2 years old, 78.8% male); 15 (26.3%) had multiple lesions and 23 (39.1%) had prior HCC treatment. The mean tumor diameter was 2.73 (±0.64) cm. The intraprocedural simulation directed additional overlapping ablations in 75.9% of tumors. Technical success and efficacy were 100% at 3-month contrast enhanced CT or MRI follow-up after the single treatment session. Cumulative incidence function estimates for 1- and 2-year LTP were 3.9% and 20.2%, respectively. CONCLUSION: This prospective study found computer-assisted guidance that simulated each ablation was both safe and efficacious. The low rate of LTP was similar to studies that employed stereotactic guidance and ablation confirmation, without requiring a second contrast enhanced study.

Ultrasound-MR fusion imaging combined with intraductal cooling via PTCD during microwave ablation of perihilar liver tumors: a retrospective pilot study.

PURPOSE: To explore the feasibility and safety of a microwave ablation (MWA) strategy involving intraductal chilled saline perfusion (ICSP) via percutaneous transhepatic cholangial drainage (PTCD) combined with ultrasound-magnetic resonance (US-MR) fusion imaging for liver tumors proximal to the hilar bile ducts (HBDs). METHODS: Patients with liver tumors proximal to the HBDs (≤5 mm) who underwent MWA at our hospital between June 2020 and April 2023 were retrospectively analyzed. The strategy of US-MR fusion imaging combined with PTCD-ICSP was used to assist the MWA procedures. The technical success, technique efficacy, local tumor progression, intrahepatic distant recurrence and complications were recorded and analyzed. RESULTS: In total, 12 patients with 12 liver tumors were retrospectively enrolled in this study. US-MR fusion imaging was utilized in all patients, and PTCD-ICSP assistance was successfully used for 4 nodules abutting HBDs (0 mm). The rates of technical success, technique efficacy, local tumor progression and intrahepatic distant recurrence were 91.7%, 83.3%, 0% and 8.3%, respectively. The major complication of biliary infection occurred in only one patient who had previously undergone left hemihepatectomy and bile-intestinal anastomosis. CONCLUSIONS: MWA for liver tumors proximal to HBDs assisted by US-MR fusion imaging combined with PTCD-ICSP was feasible and safe. This strategy made MWA of liver tumors abutting HBDs possible.

Exploring the impact of insufficient thermal ablation on hepatocellular carcinoma: NDST2 overexpression mechanism and its role in facilitating growth and invasion of residual cancer cells.

OBJECTIVE: Incomplete thermal ablation (ITA) fosters the malignancy of residual cells in Hepatocellular carcinoma (HCC) with unclear mechanisms now. This study aims to investigate the expression changes of NDST2 following ITA of HCC and its impact on residual cancer cells. METHODS: An in vitro model of heat stress-induced liver cancer was constructed to measure the expression of NDST2 using Quantitative Real-Time PCR and Western blotting experiments. The sequencing data from nude mice were used for validation. The clinical significance of NDST2 in HCC was evaluated by integrating datasets. Gene ontology and pathway analysis were conducted to explore the potential signaling pathways regulated by NDST2. Additionally, NDST2 was knocked down in heat stress-induced HCC cells, and the effects of NDST2 on these cells were verified using Cell Counting Kit-8 assays, scratch assays, and Transwell assays. RESULTS: NDST2 expression levels are elevated in HCC, leading to a decrease in overall survival rates of HCC patients. Upregulation of immune checkpoint levels in high NDST2-expressing HCC may contribute to immune evasion by liver cancer cells. Additionally, the low mutation rate of NDST2 in HCC suggests a relatively stable expression of NDST2 in this disease. Importantly, animal and cell models treated with ITA demonstrate upregulated expression of NDST2. Knockdown of NDST2 in heat stress-induced liver cancer cells results in growth inhibition associated with gene downregulation. CONCLUSION: The upregulation of NDST2 can accelerate the progression of residual HCC after ITA, suggesting a potential role for NDST2 in the therapeutic efficacy and prognosis of residual HCC.

Directional microwave ablation in spine: experimental assessment of computational modeling.

BACKGROUND: Despite the theoretical advantages of treating metastatic bone disease with microwave ablation (MWA), there are few reports characterizing microwave absorption and bioheat transfer in bone. This report describes a computational modeling-based approach to simulate directional microwave ablation (dMWA) in spine, supported by ex vivo and pilot in vivo experiments in porcine vertebral bodies. MATERIALS AND METHODS: A 3D computational model of microwave ablation within porcine vertebral bodies was developed. Ex vivo porcine vertebra experiments using a dMWA applicator measured temperatures approximately 10.1 mm radially from the applicator in the direction of MW radiation (T1) and approximately 2.4 mm in the contra-lateral direction (T2). Histologic assessment of ablated ex vivo tissue was conducted and experimental results compared to simulations. Pilot in vivo experiments in porcine vertebral bodies assessed ablation zones histologically and with CT and MRI. RESULTS: Experimental T1 and T2 temperatures were within 3-7% and 11-33% of simulated temperature values. Visible ablation zones, as indicated by grayed tissue, were smaller than those typical in other soft tissues. Posthumous MRI images of in vivo ablations showed hyperintensity. In vivo experiments illustrated the technical feasibility of creating directional microwave ablation zones in porcine vertebral body. CONCLUSION: Computational models and experimental studies illustrate the feasibility of controlled dMWA in bone tissue.

Thermal ablation for the treatment of malignant thyroid nodules: present and future.

As the utilization of high-resolution imaging modalities, such as ultrasound, becomes increasingly prevalent, there has been a swift rise in the detection rates of malignant thyroid nodules (MTC). Surgery remains the cornerstone of standard treatment for these nodules. However, the advent and evolution of thermal ablation (TA) techniques, encompassing radiofrequency ablation, laser ablation, and microwave ablation, have emerged as a novel therapeutic avenue for patients with MTC, particularly for those deemed unsuitable for surgery due to high risks or for those who refuse surgery. Presently, TA has been validated as an efficacious and safe intervention for both benign thyroid nodules and a subset of MTC. An expanding body of research has been dedicated to broadening the applicability of TA, initially from recurrent thyroid cancer and lymph nodes to now encompass isolated papillary thyroid microcarcinomas (PTMC) alongside a comprehensive exploration into the expanded parameters such as size, number, and location of PTMC, and its applicability in other types of thyroid cancer. This review provides a detailed synthesis of the clinical evidence about the use of TA in the management of MTC, as endorsed by current guidelines. It further delves into the ongoing research efforts aimed at extending its indications and discusses the prospective implications and challenges of integrating TA into the clinical management paradigms for MTC.

The value of susceptibility weighted imaging for immediate assessing the hyperacute outcome of MRgFUS ablation for uterine fibroids: a preliminary study.

PURPOSE: To investigate the value of susceptibility weighted imaging (SWI) for assessing the hyperacute outcome of ablation of uterine fibroids immediately after magnetic resonance-guided focused ultrasound (MRgFUS) treatment. METHODS: This retrospective imaging study included patients who underwent SWI and contrast-enhanced (CE) MR within 15 min of MRgFUS ablation for uterine fibroids. Two readers independently assessed the SWI features of ablative lesions and their association with the non-perfused volume (NPV) ratio. The intraclass correlation coefficient (ICC) and diagnostic value of SWI findings were calculated. RESULTS: A total of 27 uterine fibroids from 21 participants (mean age 40.1 ± 7.2 years) were analyzed. 51.9% (14/27) leiomyomas had NPV ratio ≥90%. In post-ablation SWI images, the interobserver ICC for the relative signal intensity and hypointense peripheral rim were 0.613 and 0.843, respectively (both p < .001). There was a significant difference in the prevalence of hypointense peripheral rim in leiomyomas with NPV ratio ≥90% and < 90% (p < .01), while the prevalence of relative signal intensity showed no significant difference (p > .05). When using the complete hypointense peripheral rim as a diagnostic criterion to identify NPV ratio ≥ 90%, readers 1 and 2 showed diagnostic sensitivity, specificity, and accuracy of 85.7%, 76.9%, 81.5%, and 78.6%, 76.9%, 77.8%, respectively. CONCLUSION: Identifying a complete hypointense peripheral rim on SWI may be a potential imaging marker for assessing the hyperacute outcome of uterine fibroids ablation by MRgFUS, specifically in determining whether the NPV ratio is ≥90%.

Magnetic hybrid Pd/Fe-oxide nanoparticles meet the demands for ablative thermo-brachytherapy.

OBJECTIVE: To investigate the potential of hybrid Pd/Fe-oxide magnetic nanoparticles designed for thermo-brachytherapy of breast cancer, considering their specific loss power (SLP) and clinical constraints in the applied magnetic field. METHODS: Hybrid nanoparticles consisting of palladium-core and iron oxide shell of increasing thickness, were suspended in water and their SLPs were measured at varying magnetic fields (12-26 mT peak) and frequencies (50-730 kHz) with a commercial alternating magnetic field generator (magneTherm™ Digital, nanoTherics Ltd.). RESULTS: Validation of the heating device used in this study with commercial HyperMag-C nanoparticles showed a small deviation (±4%) over a period of 1 year, confirming the reliability of the method. The integration of dual thermometers, one in the center and one at the bottom of the sample vial, allowed monitoring of homogeneity of the sample suspensions. SLPs measurements on a series of nanoparticles of increasing sizes showed the highest heating for the diameter of 21 nm (SLP = 225 W/g) at the applied frequencies of 346 and 730 kHz. No heating was observed for the nanoparticles with the size <14 nm, confirming the importance of the size-parameter. The heating ability of the best performing Pd/Fe-oxide-21 was calculated to be sufficient to ablate tumors with a radius ±4 and 12 mm using 10 and 1 mg/mL nanoparticle concentration, respectively. CONCLUSIONS: Nanoparticles consisting of non-magnetic palladium-core and magnetic iron oxide shell are suitable for magnetic hyperthermia/thermal ablation under clinically safe conditions of 346 kHz and 19.1 mT, with minimal eddy current effects in combination with maximum SLP.

Noninvasive release of tendons using MRI guided focused ultrasound: a hybrid therapy using long-pulse focused ultrasound followed by thermal ablation.

INTRODUCTION: Magnetic Resonance-guided Focused Ultrasound (MRgFUS) thermal ablation is an effective noninvasive ultrasonic therapy to disrupt in vivo porcine tendon but is prone to inducing skin burns. We evaluated the safety profile of a novel hybrid protocol that minimizes thermal spread by combining long-pulse focused ultrasound followed by thermal ablation. METHODS: In-vivo Achilles tendons (hybrid N = 15, thermal ablation alone N = 21) from 15 to 20 kg Yorkshire pigs were randomly assigned to 6 treatment groups in two studies. The first (N = 21) was ablation (600, 900, or 1200 J). The second (N = 15) was hybrid: pulsed FUS (13.5 MPa peak negative pressure) followed by ablation (600, 900, or 1200 J). Measurements of ankle range of motion, tendon temperature, thermal dose (240 CEM43), and assessment of skin burn were performed in both groups. RESULTS: Rupture was comparable between the two protocols: 1/5 (20%), 5/5 (100%) and 5/5 (100%) for hybrid protocol, compared to 2/7 (29%), 6/7 (86%) and 7/7 (100%) for the ablation-only protocol with energies of 600, 900, and 1200 J, respectively. The hybrid protocol produced lower maximum temperatures, smaller areas of thermal dose, fewer thermal injuries to the skin, and fewer full-thickness skin burns. The standard deviation for the area of thermal injury was also smaller for the hybrid protocol, suggesting greater predictability. CONCLUSION: This study demonstrated a hybrid MRgFUS protocol combining long-pulse FUS followed by thermal ablation to be noninferior and safer than an ablation-only protocol for extracorporeal in-vivo tendon rupture for future clinical application for noninvasive release of contracted tendon.

Expanding management strategies for cervical precancerous lesions in resource-limited settings: insights from a training center in a district hospital in Ghana.

BACKGROUND: Cervical cancer continues to disproportionately burden women in low/middle-income countries like Ghana. We examined treatment patterns and histopathological outcomes among women screened using visual inspection with acetic acid (VIA) and/or mobile colposcopy who subsequently underwent thermal ablation, large loop excision of the transformation zone (LLETZ), or cold knife conization at the Cervical Cancer Prevention and Training Centre, Battor. We also assessed the prevalence of cervical intraepithelial neoplasia 2+ (CIN2+) or micro-invasive disease and their associated factors for women who underwent excisional treatments. The treatment choices for cervical precancerous lesions suitable for resource-limited settings have also been described from the perspective of a center that manages a heterogenous population. METHODS: We conducted an analysis of secondary data collected between June 2016 and June 2023 among women with positive findings on VIA or mobile colposcopy who subsequently underwent thermal ablation or large loop excision of the transformation zone (LLETZ). The prevalence of histopathology outcomes, including no dysplasia, CIN1 - 3, and micro-invasive disease, were estimated with 95% confidence intervals (CIs). Factors associated with histopathological findings were modeled using multinomial logistic regression. RESULTS: For the study period, 14 (10.6%) of the total 132 participants underwent cervical lesion treatment at outreach locations, all via thermal ablation. The remaining 118 (89.4%) were treated at the Catholic Hospital, Battor using LLETZ (n = 66, 55.9%), thermal ablation (n = 51, 43.2%), and cold knife conization (n = 1, 0.9%). Among 65 women with histopathology reports, the most frequent histopathological finding was no dysplasia (47.7%; 95% CI, 35.1 - 60.5), followed by CIN2 and CIN3 (20.0%; 95% CI, 11.1 - 31.8 each), CIN1 (7.7%; 95% CI, 2.5 - 17.0) and micro-invasion (4.6%; 95% CI, 1.0 - 12.9). Those with micro-invasive disease were significantly older than those with CIN1, CIN2, and CIN3 (p = 0.036, 0.022, 0.009, respectively), but not significantly older than those who showed no dysplasia (p = 0.088). For each unit increase in age, the likelihood of CIN3 was relatively significantly reduced compared to no dysplasia (crude relative risk ratio [RRR] = 0.93; 95% CI, 0.86 - 0.99). This association was neither observed with the remaining histopathological groups nor for parity and persisted after controlling for parity (adjusted RRR = 0.92; 95% CI, 0.85 - 0.99; p = 0.025). CONCLUSION: This paper largely demonstrates treatment options available to women and practitioners in LMICs. The high combined prevalence of high-grade precancerous lesions and micro-invasive disease underscores the need to increase cervical cancer awareness that would enhance screening attendance and hasten efforts at moving from opportunistic to organized screening in Ghana. This will enhance early cervical lesion detection and treatment, while simultaneously re-evaluating and cutting down on unnecessary treatment.

Potential of Thermal Ablation Combined with Immunotherapy in Peripheral Lung Tumors: A Review and Prospect.

BACKGROUND: Lung tumors are prevalent malignancies associated with a high mortality rate, imposing significant medical and societal burdens. Although immunotherapy shows promise in improving survival, response rates are relatively modest. Thermal ablation can not only eliminate tumor cells directly but also enhance antitumor immunity response, thus manifesting a remarkable propensity to synergize with immunotherapy. SUMMARY: In this review, we provided a brief overview of the application of thermal ablation in peripheral lung tumors. We summarized the patient selection of thermal ablation. We highlighted the potential of thermal ablation to augment the antitumor immune response, offering a promising avenue for combined therapies. We summarized studies assessing the synergistic effects of thermal ablation and immunotherapy in preclinical and clinical settings. Lastly, we underscored the urgent issues that warrant in-depth exploration when applying thermal ablation and immunotherapy to lung tumor patients. KEY MESSAGES: This review emphasized the prospects of using thermal ablation combined with immunotherapy in patients with peripheral lung tumors. However, further research is needed to enhance and optimize this treatment strategy.

Compression Therapy after Thermal Ablation of Varicose Veins: A Meta-Analysis.

OBJECTIVE: To investigate whether compression therapy after thermal ablation of varicose veins can improve the prognosis of patients. METHODS: Systematic research were applied for Chinese and English electronic databases(PubMed, Web of Science, Cochrane Library, CNKI, Wanfang, VIP Databases). Eligible prospective studies that comparing the efficacy of compression therapy and non-compression therapy on patients after thermal ablation of varicose veins were included. The interest outcome such as pain, quality of life (QOL), venous clinical severity score (VCSS), time to return to work and complications were analyzed. RESULTS: 10 studies were of high quality, and randomized controlled trials involving 1,545 patients met the inclusion criteria for this study. At the same time, the meta-analysis showed that the application of compression therapy improved pain (SMD: -0.51, 95% CI: -0.95, -0.07) but exhibited no statistically significant effect on QOL (SMD: 0.04, 95% CI: -0.08, 0.16), VCSS (MD: -0.05, 95% CI: -1.19, 1.09), time to return to work (MD: -0.43, 95% CI: -0.90, 0.03), total complications (RR: 0.54, 95% CI: 0.27, 1.09), and thrombosis (RR: 0.71, 95% CI: 0.31, 1.62). CONCLUSION: Compression therapy after thermal ablation of varicose veins can slightly relieve pain, but it has not been found to be associated with improvement in other outcomes.

Update on musculoskeletal applications of magnetic resonance-guided focused ultrasound.

Magnetic resonance-guided focused ultrasound (MRgFUS) is a noninvasive, incisionless, radiation-free technology used to ablate tissue deep within the body. This technique has gained increased popularity following FDA approval for treatment of pain related to bone metastases and limited approval for treatment of osteoid osteoma. MRgFUS delivers superior visualization of soft tissue targets in unlimited imaging planes and precision in targeting and delivery of thermal dose which is all provided during real-time monitoring using MR thermometry. This paper provides an overview of the common musculoskeletal applications of MRgFUS along with updates on clinical outcomes and discussion of future applications.