Real-time non-invasive control of ultrasound hyperthermia using high-frequency ultrasonic backscattered energy inex vivotissue andin vivoanimal studies.

Objective.A reliable, calibrated, non-invasive thermometry method is essential for thermal therapies to monitor and control the treatment. Ultrasound (US) is an effective thermometry modality due to its relatively high sensitivity to temperature changes, and fast data acquisition and processing capabilities.Approach.In this work, the change in backscattered energy (CBE) was used to control the tissue temperature non-invasively using a real-time proportional-integral-derivative (PID) controller. A clinical high-frequency US scanner was used to acquire radio-frequency echo data fromex vivoporcine tissue samples andin vivomice hind leg tissue while the tissue was treated with mild hyperthermia by a focused US applicator. The PID controller maintained the focal temperature at approximately 40 °C for about 4 min.Main results.The results show that the US thermometry based on CBE estimated by a high-frequency US scanner can produce 2D temperature maps of a localized heating region and to estimate the focal temperature during mild hyperthermia treatments. The CBE estimated temperature varied by an average of ±0.85 °C and ±0.97 °C, compared to a calibrated thermocouple, inex vivoandin vivostudies, respectively. The mean absolute deviations of CBE thermometry during the controlled hyperthermia treatment were ±0.45 °C and ±0.54 °C inex vivoandin vivo,respectively.Significance.It is concluded that non-invasive US thermometry via backscattered energies at high frequencies can be used for real-time monitoring and control of hyperthermia treatments with acceptable accuracy. This provides a foundation for an US mediated drug delivery system.

Predictors of symptomatic relief in water vapor thermal therapy for prostatic hyperplasia: 36-month prospective study.

PURPOSE: Existing literature lacks an analysis of factors predicting the achievement of minimum clinically important differences (MCID) after water vapor thermal therapy (WVTT) for prostatic hyperplasia. This study aims to identify these predictors over a 36-month post-WVTT period. METHODS: This prospective single surgeon case series assessed male patients receiving WVTT. Eligibility criteria included being at least 45 years old, having an estimated prostate volume (EPV) of 30-80 cc, an International Prostate Symptom Score (IPSS) of 12 points or more, and a maximum urinary flow rate (Qmax) under 16 mL/sec. MCID, representing the smallest symptomatic improvement perceived by patients, was calculated using the distribution-based method, considering half a standard deviation of baseline IPSS scores. Correlation and linear regression analyses assessed MCID attainment. Multivariable logistic regression evaluated MCID achievement, considering multicollinearity, heteroskedasticity, and normality. RESULTS: Of 206 men with a median 29.1-month follow-up (Range: 24-36), 13.6% didn't achieve MCID for IPSS, and 7.2% for QoL scores. Significant hindrances to MCID attainment for IPSS were a large median lobe (> 10 mm protrusion) (OR = 3.01, 95% CI: 2.3-3.72), increased median lobe treatments (OR = 1.73, 95% CI: 1.23-2.35), and high preoperative irritative IPSS scores (OR = 1.25, 95% CI: 1.13-1.38). Factors for QoL MCID non-achievement included age over 75 (OR = 1.25, 95% CI: 1.13-1.38), a large median lobe (OR = 1.87, 95% CI: 1.62-2.01), and EPV over 60 cc (OR = 1.55, 95% CI: 1.16-1.97). A 6.3% surgical re-intervention rate was noted. CONCLUSIONS: The characteristics of the median lobe as well as the severity of lower urinary tract symptoms are crucial for treatment success. These should be integral to preoperative assessments and patient discussions on treatment options.

Comparisons of computer simulations and experimental data for capacitive hyperthermia using different split-phantoms.

INTRODUCTION: Several positive clinical trials have demonstrated that capacitive hyperthermia (CHT) improves the effectiveness of radiation therapy for the treatment of various cancer entities. However, the ability of CHT to induce significant heating throughout the body is under debate. OBJECTIVES: To perform a pilot study involving comparisons of computer simulations and experimental data using different split-phantoms to validate hyperthermia treatment modeling for pre-planning for a clinical CHT system and to investigate the feasibility of split-phantom measurements in capacitive hyperthermia. MATERIALS AND METHODS: The CHT system EHY-2030 (Oncotherm, Budapest, Hungary) was used. The system provides two electrode sizes, but only the smaller electrode, indicated as D200 electrode, was investigated in this pilot study. Horizontally and vertically splittable, different multi-slice phantoms with dielectric material properties simulating muscle and electrically low conductive fat were produced and heated. During the heating procedure, temperature-time curves were measured, and thermal images were captured. Specific absorption rate values were derived from the temperature rise (TR) values. Concomitantly, computer field simulations utilizing a detailed CAD-based model of the CHT system were performed using the simulation platform Sim4Life and compared with measurements. RESULTS: For the investigated electrode D200 the system power of 75 W was applied, which is half of the maximum power of 150 W and lies in the range of usual values for this electrode applied in patient treatments in our clinic. For 75 W, a heating of 3.6 °C in 6 min in a depth of 1 cm in an agar-based, muscle tissue-equivalent phantom was achieved. The addition of a 1 cm thick, synthetic, low dielectric fat layer reduced the TR up until a depth of 8.5 cm by on average around 38% (from 8.5 cm onwards the absolute local TR is similar, deviations are ≤0.1 °C). In terms of point-to-point absolute SAR comparison (without any normalization), up to a depth of 11 cm in the phantoms central vertical plot, the simulation differs from the measured TR points by on average 25% (ranging from 7% to 36%) for the homogeneous phantom and by on average 43% (ranging from 26% to 60%) for the inhomogeneous phantom. CONCLUSION: Computer simulations and experimental data were compared for the CHT system EHY-2030 using the D200 electrode, applying a thermal imaging technique for different vertically splittable phantoms. This pilot study data can be used as a guidance regarding the expected heating for this commonly used electrode size but also to further elucidate the significance of non-thermal anticancer effects. Further studies are needed for different sizes and geometries of electrodes and phantoms.

Mild hyperthermia upregulates PD-L1 in the tumor microenvironment and enhances antitumor efficacy of PD-L1 blockade in murine squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) has a low five-year survival rate because of its high rate of recurrence and metastasis. After surgical resection or radiation, the main treatments for HNSCC, patients sometimes experience functional or aesthetic disorders. Therefore, there is a great demand for the development of non-surgical treatment strategies to improve clinical outcomes and patients' quality of life. One such non-surgical treatment is mild hyperthermia (mHT). Many studies have investigated combination treatments with mHT and immune checkpoint inhibitors in preclinical settings. However, there have been no detailed reports on the effects of mHT on immune checkpoint molecules. Here, we investigated the effects of mHT on the tumor microenvironment (TME), particularly on programmed cell death receptor-1 (PD-1)/programmed cell death ligand-1 (PD-L1), in SCCVII cells and a squamous cell carcinoma mouse model. First, we found that PD-L1 mRNA levels and surface PD-L1 expression significantly increased after mHT. Second, a single tumor model was used to determine the effect of HT on the TME. mHT enhanced the accumulation of CD4+ and CD8+ T cells, elevated PD-L1 expression in the TME, and decreased the PD-1 positive rate of CD4+ T cells. Finally, using a bilateral tumor model, we found that anti-PD-L1 monotherapy and combination therapy resulted in longer survival than the isotype control or mHT monotherapy. Moreover, the combination therapy resulted in a significantly higher survival rate than anti-PD-L1 monotherapy. In conclusion, our findings elucidate changes in PD-L1 expression in the TME and strengthen the rationale for mHT and PD-L1 blockade combination therapy.

One-Pot Synthesis of Fe-Norepinephrine Nanoparticles for Synergetic Thermal-Enhanced Chemodynamic Therapy.

Chemodynamic therapy (CDT) is an innovative and burgeoning strategy that utilizes Fenton-Fenton-like chemistry and specific microenvironments to produce highly toxic hydroxyl radicals (•OH), with numerous methods emerging to refine this approach. Herein, we report a coordination compound, Fe-norepinephrine nanoparticles (Fe-NE NPs), via a one-pot synthesis. The Fe-NE NPs are based on ferrous ions (Fe2+) and norepinephrine, which are capable of efficient Fe2+/Fe3+ delivery. Once internalized by tumor cells, the released Fe2+/Fe3+ exerts the Fenton reaction to specifically produce toxic •OH. Moreover, the internal photothermal conversion ability of Fe-NE NPs allows us to simultaneously introduce light to trigger local heat generation and then largely improve the Fenton reaction efficiency, which enables a synergetic photothermal and chemodynamic therapy to realize satisfactory in vivo antitumor efficiency. This proof-of-concept work offers a promising approach to developing nanomaterials and refining strategies for enhanced CDT against tumors.

Key Biophysical and Physiological Properties Impacting the Oxygenation Status of Breast Cancers During Thermo-radiotherapy.

Mild hyperthermia at 39-43 °C for 30-60 min is applied locoregionally to improve the oxygenation status of recurrent breast cancers, thus enhancing the efficacy of radio-, chemo-, and immunotherapy. In this context, estimated (or even conflicting) data are often used in computational modelling of tumour oxygenation and simulation of O2 transport. In this chapter, we present information that may help to improve adjuvant thermotherapy delivered immediately prior to radiotherapy of recurrent breast cancers. Data are preferentially derived from clinical investigations; in some cases, measurements in experimental breast cancers are included.The biophysical properties presented for healthy, mostly postmenopausal, human breast (composite glandular-adipose-fibrous tissue) measured under normothermic (NT) conditions and in therapeutically heated breast cancers include tissue water content and tissue density. In general, averaged values of parameters reported for NT conditions are higher in breast cancers than in normal breast tissue, i.e., all ratios breast cancer/normal breast are >1. Mean values observed in breast cancers during mild hyperthermia (mHT) are consistently higher than those in NT tumours. Parameters determining convective transports in healthy breast tissue and breast cancer include blood flow rates, blood volume, exchanging water space, arterio-venous shunt flow, interstitial fluid flow rate, interstitial fluid pressure, microvascular permeability, interstitial hydraulic conductivity, and interstitial flow velocity. In general, averaged values of parameters measured under NT conditions are higher in breast cancers than in healthy breast. Except for interstitial fluid pressure, these values increase upon mHT treatment of cancers. Prime factors determining and describing the oxygenation status of the healthy breast, and in NT- versus mHT-treated breast cancers, include: oxygen (O2) delivery rates, O2- extractions, O2- consumption rates, subepidermal microvascular HbO2, tissue oxygen solubility, oxygen diffusion coefficients, mean O2 partial pressures pO2, hypoxic fractions HF <5 mmHg, oxygen enhancement ratio, and mitochondrial ROS production. With the exception of the mean pO2, O2 extraction rate and tissue O2 saturation all parameters listed are distinctly higher in breast cancers under NT conditions compared to normal breast. Mild hyperthermia results in therapeutically relevant improvements of the oxygenation status of cancers and enhances mitochondrial ROS production, thus improving radiosensitivity. Note: The oxygenation status of the healthy (postmenopausal) breast is very similar to that of the normal human subcutis.

Infrared radiation for cancer hyperthermia: the light to brighten up oncology.

INTRODUCTION: Cancer constitutes the greatest public health threat to humans, as its incidence and mortality rates continue to increase worldwide. With the development of medical physics, more practitioners focus on the direct and indirect anti-tumor effects of physical factors. Infrared radiation (INR) is currently the most rapidly developing physical therapy method for tumors and has become a favored target for many oncologists and researchers owing to its advantages of high efficiency, low toxicity, and strong feasibility. AREAS COVERED: This work provides a comprehensive collection of the latest information on INR anti-tumor research, drawing from public medical databases (PubMed, Web of Science, Embase, and Clinical Trials) from the last 10 years (2014 to 2024), and encompassing both basic and clinical research in oncology and physics. This article reviews the application of INR in tumor hyperthermia, summarizes and analyzes the practical value of INR for tumor treatment, and discusses future development trends to provide valuable assistance for the subsequent development of oncology. EXPERT OPINION: Currently, INR has continuously accumulated excellent data in the field of tumor hyperthermia, bringing practical survival benefits to patients with cancer, and playing an important role in basic and clinical cancer research.

A 3-arm randomized control trial to compare the efficacy of re-circulant hyperthermic intravesical chemotherapy versus conventional intravesical mitomycin C and BCG therapy for intermediate-risk non-muscle invasive bladder cancer.

INTRODUCTION: To evaluate the efficacy and side effects of re-circulant hyperthermic intravesical chemotherapy versus conventional treatments for intermediate risk non-muscle invasive bladder cancer (NMIBC). METHODS: A randomized 3-arm, parallel group trial was conducted at a single tertiary care centre. 135 patients with low-grade intermediate-risk cancer, having undergone complete resection of bladder tumor were included. Patients were assigned 1:1:1, to receive intra-vesical chemo-hyperthermia (C-HT), mitomycin-C (MMC) or BCG therapy. There was no treatment crossover. Patients were followed up with check cystoscopy every 3 months for histopathological recurrence. RESULTS: The three arms were comparable in terms of age, gender, tumor size, number of tumors and clinical stage or grade of tumors. Mean tumor size was 2.58 (± 0.88) cm and the mean number of tumors resected was 2.04 (± 1.02) (Range 1-5). There was no significant difference between the various groups for tumor recurrence (χ2 = 1.96, p = 0.375) or time to recurrence (13.6 vs. 10.8 vs. 9.8 months, p = 0.844) though incidence of non-healing necrotic area was higher with C-HT (22.2% vs. 11.1% and 4.8%, χ2 = 6.093, p = 0.048). Median (IQR) follow up period was 26 (12-52) months. Treatment discontinuation or drug intolerance was significantly higher in BCG arm (p = 0.03). CONCLUSIONS: Intravesical C-HT with MMC, conventional MMC and BCG are equally effective and comparable alternatives for intravesical therapy in low-grade intermediate-risk NMIBC. Higher incidence of non-healing resection site with C-HT and higher local symptoms with BCG are a concern.

Design of multi-modal antenna arrays for microwave hyperthermia and 1H/19F MRI monitoring of drug release.

This simulation-based study presented a novel hybrid RF antenna array designed for neck cancer treatment within a 7T MRI system. The proposed design aimed to provide microwave hyperthermia to release 19F-labeled anticancer drugs from thermosensitive liposomes, facilitating drug concentration monitoring through 19F imaging and enabling 1H anatomical imaging and MR thermometry for temperature control. The design featured a bidirectional microstrip for generating the magnetic |B1|-fields required for 1H and 19F MR imaging, along with a patch antenna for localized RF heating. The bidirectional microstrip was operated at 300 MHz and 280 MHz through the placement of excitation ports at the ends of the antenna and an asymmetric structure along the antenna. Additionally, a patch antenna was positioned at the center. Based on this setup, an array of six antennas was designed. Simulation results using a tissue-mimicking simulation model confirmed the intensity and uniformity of |B1|-fields for both 19F and 1H nuclei, demonstrating the suitability of the design for clinical imaging. RF heating from the patch antennas was effectively localized at the center of the cancer model. In simulations with a human model, average |B1|-fields were 0.21 µT for 19F and 0.12 µT for 1H, with normalized-absolute-average-deviation values of 81.75% and 87.74%, respectively. Hyperthermia treatment was applied at 120 W for 600 s, achieving an average temperature of 40.22°C in the cancer model with a perfusion rate of 1 ml/min/kg. This study demonstrated the potential of a hybrid antenna array for integrating 1H MR, 19F drug monitoring, and hyperthermia.

Tuning the physical properties of ternary alloys (NiCuCo) for in vitro magnetic hyperthermia: experimental and theoretical investigation.

Most of published research on magnetic hyperthermia focused on iron oxides, ferrites, and binary alloy nanostructures, while the ternary alloys attracted much limited interest. Herein, we prepared NiCuCo ternary alloy nanocomposites with variable compositions by mechanical alloying. Physical properties were fully characterized by XRD, Rietveld analysis, XPS, SEM/EDX, TEM, ZFC/FC and H-M loops. DFT calculations were used to confirm the experimental results in terms of structure and magnetism. The results showed that the fabricated nanoalloys are face centered cubic (FCC) with average core sizes of 9-40 nm and behave as superparamagnetic with saturation in the range 4.67-42.63 emu/g. Langevin fitting corroborated the superparamagnetic behavior, while law of approach to saturation (LAS) was used to calculate the magnetic anisotropy constants. Heating effciencies were performed under an alternating magnetic field (AMF, H0 = 170 Oe and f = 332.5 kHz), and specific absorption rate (SAR) values were determined. The highest magnetic saturation (Ms), heating potentials, and SAR values were attained for Ni35Cu30Co35 containing the lowest Cu but highest Ni and Co percentages, and the least for Ni15Cu70Co15. Importantly, the nanoalloys reached the required temperatures for magnetic hyperthermia (42 °C) in relatively short times. We also showed that heat dissipiation can be simply tuned by changing many parameters such as concentration, field amplitude, and frequency. Finally, cytotoxicity viability assays against two different breast cancer cell lines treated with Ni25Cu50Co25 nanoalloy in the presence and absence of AMF were investigated. No significant decrease in cancer cell viability was observed in the absence of AMF. When tested against tumorigenic KAIMRC2 breast cancer cells under AMF, the NiCuCo nanoalloy was found to be highly potent to the cells (~ 2-fold enhancement), killing almost all the cells in short times (20 min) and clinically-safe AC magnetic fields. These findings strongly suggest that the as-prepared ternary NiCuCo nanoalloys hold great promise for potential magnetically-triggered cancer hyperthermia.

Experimental Validation of Realistic Measurement Setup for Quantitative UWB-Guided Hyperthermia Temperature Monitoring.

Hyperthermia induces slight temperature increase of 4-8 °C inside the tumor, making it more responsive to radiation and drugs, thereby improving the outcome of the oncological treatment. To verify the level of heat in the tumor and to avoid damage of the healthy tissue, methods for non-invasive temperature monitoring are needed. Temperature estimation by means of microwave imaging is of great interest among the scientific community. In this paper, we present the results of experiments based on ultra-wideband (UWB) M-sequence technology. Our temperature estimation approach uses temperature dependency of tissue dielectric properties and relation of UWB images to the reflection coefficient on the boundary between tissue types. The realistic measurement setup for neck cancer hyperthermia considers three antenna arrangements. Data are processed with Delay and Sum beamforming and Truncated Singular Value Decomposition. Two types of experiments are presented in this paper. In the first experiment, relative permittivity of subsequently replaced tumor mimicking material is estimated, and in the second experiment, real temperature change in the tumor imitate is monitored. The results showed that the presented approach allows for qualitative as well as quantitative permittivity and temperature estimation. The frequency range for temperature estimation, preferable antenna configurations, and limitations of the method are indicated.

Paclitaxel hyperthermia suppresses gastric cancer migration through MiR-183-5p/PPP2CA/AKT/GSK3ß/ß-catenin axis.

BACKGROUND: Gastric cancer (GC), a prevalent malignant tumor which is a leading cause of death from malignancy around the world. Peritoneal metastasis accounts for the major cause of mortality in patients with GC. Despite hyperthermia intraperitoneal chemotherapy (HIPEC) improves the therapeutic effect of GC, it's equivocal about the mechanism under HIPEC. METHODS: MiR-183-5p expression was sifted from miRNA chip and detected in both GC patients and cell lines by qRT-PCR. Gene interference and rescue experiments were performed to identified biological function in vitro and vivo. Next, we affirmed PPP2CA as targeted of miR-183-5p by dual luciferase reporter assay. Finally, the potential relationship between HIPEC and miR-183-5p was explored. RESULTS: MiR-183-5p is up-regulated in GC and associated with advanced stage and poor prognosis. MiR-183-5p accelerate GC migration in vitro which is influenced by miR-183-5p/PPP2CA/AKT/GSK3ß/ß-catenin Axis. HIPEC exerts migration inhibition via attenuating miR-183-5p expression. CONCLUSION: MiR-183-5p can be used as a potential HIPEC biomarker in patients with CC.

In vivo electrical properties of the healthy liver and the hepatic tumor in a mouse model between 1 Hz and 1 MHz during a thermal treatment.

Objective: Understansding the changing patterns of in vivo electrical properties for the target tissue is crucial for the accurate temperature monitoring and the treatment efficacy in thermal therapy. Our research aims to investigate the changing patterns and the reversibility of in vivo electrical properties for both healthy livers and liver tumors in a mouse model over a frequency range of 1 Hz to 1 MHz at temperatures between 30 °C to 90 °C.Methods and materials: The mice were anesthetized and the target organ was exposed. An 808-nm near-infrared laser was employed as the heating source to heat the organ in vivo. The four-needle electrode, connected to an impedance analyzer, was utilized to obtain the impedance at varying temperatures, which were monitored by a thermocouple.Results: The findings indicated a gradual decline in impedance with an increase in temperature. Furthermore, the impedance was normalized to that at 30 °C, and the real part of the normalized impedance was defined as the k-values, which range from 0 to 1. The results demonstrated a linear correlation between k-values and temperatures (R2 > 0.9 for livers and R2 > 0.8 for tumors). Significant differences were observed between livers and tumors at 1, 10 and 50 kHz (p < 0.05). Additionally, it was demonstrated that the electrical properties could be reversed when the temperature was below or equal to 45 °C.Conclusion: We believe that these results will contribute to the advancement of radiofrequency ablation systems and the development of techniques for temperature monitoring during liver thermal treatment.

Non-inferiority, randomised, open-label clinical trial on the effectiveness of transurethral microwave thermotherapy compared to prostatic artery embolisation in reducing severe lower urinary tract symptoms in men with benign prostatic hyperplasia: study protocol for the TUMT-PAE-1 trial.

BACKGROUND: One-fourth of men older than 70 years have lower urinary tract symptoms (LUTS) that impair their quality of life. Transurethral resection of the prostate (TURP) is considered the gold standard for surgical treatment of LUTS caused by benign prostatic hyperplasia (BPH) that cannot be managed conservatively or pharmacologically. However, TURP is only an option for patients fit for surgery and can result in complications. Transurethral microwave thermotherapy (TUMT) and prostatic artery embolisation (PAE) are alternative minimally invasive surgical therapies (MISTs) performed in an outpatient setting. Both treatments have shown to reduce LUTS with a similar post-procedure outcome in mean International Prostate Symptom Score (IPSS). It is however still unknown if TUMT and PAE perform equally well as they have never been directly compared in a randomised clinical trial. The objective of this clinical trial is to assess if PAE is non-inferior to TUMT in reducing LUTS secondary to BPH. METHODS: This study is designed as a multicentre, non-inferiority, open-label randomised clinical trial. Patients will be randomised with a 1:1 allocation ratio between treatments. The primary outcome is the IPSS of the two arms after 6 months. The primary outcome will be evaluated using a 95% confidence interval against the predefined non-inferiority margin of + 3 points in IPSS. Secondary objectives include the comparison of patient-reported and functional outcomes at short- and long-term follow-up. We will follow the patients for 5 years to track long-term effect. Assuming a difference in mean IPSS after treatment of 1 point with an SD of 5 and a non-inferiority margin set at the threshold for a clinically non-meaningful difference of + 3 points, the calculated sample size was 100 patients per arm. To compensate for 10% dropout, the study will include 223 patients. DISCUSSION: In this first randomised clinical trial to compare two MISTs, we expect non-inferiority of PAE to TUMT. The most prominent problems with MIST BPH treatments are the unknown long-term effect and the lack of proper selection of candidates for a specific procedure. With analysis of the secondary outcomes, we aspire to contribute to a better understanding of durability and provide knowledge to guide treatment decisions. TRIAL REGISTRATION: ClinicalTrials.gov NCT05686525. Registered on January 17, 2023, https://clinicaltrials.gov/study/NCT05686525 .

Postoperative early laboratory changes and follow-up process of patients underwent hyperthermic intrathoracic chemotherapy.

BACKGROUND: The aim of combining hyperthermic intrathoracic chemotherapy (HITHOC) with surgery is to achieve local control in patients with pleural malignancies. Liver and kidney dysfunction resulting from this procedure have been reported in the literature. The objective of the study is to examine whether the laboratory abnormalities observed during the initial period persist until day 30. METHODS: The study conducted a retrospective analysis of the blood glucose levels, renal function markers, and hepatic function markers of 30 patients who underwent pleurectomy-decortication and HITHOC for pleural mesothelioma from January 2010 to April 2022. The measurements were taken in the postoperative period on the first four and 30th days. The study analyzed the initial and final laboratory results caused by the procedure. RESULTS: Out of the total of 30 patients, 29, 28, 14, and 12 patients had elevated glucose levels on the first four days after the surgery, respectively. There was no association between glucose abnormalities and preoperative-postoperative diabetes mellitus. A minority of patients experienced atypical alterations in kidney and liver functions during the initial postoperative period. There was no apparent relationship between the renal and hepatic functions in the early and late periods after the surgery. CONCLUSION: Although there were fluctuations in glucose levels and renal and hepatic functions in the early period after surgery, there were no persistent alterations in these parameters by day 30. Elevated glucose levels during the early period were not associated with the development of newly diagnosed diabetes mellitus after surgery. The findings of our study provide evidence that HITHOC is a favorable and well-tolerated treatment option for mesothelioma.

Dual-Modal Near-Infrared Organic Nanoparticles: Integrating Mild Hyperthermia Phototherapy with Fluorescence Imaging.

Purpose: Our study seeks to develop dual-modal organic-nanoagents for cancer therapy and real-time fluorescence imaging, followed by their pre-clinical evaluation on a murine model. Integrating NIR molecular imaging with nanotechnology, our aim is to improve outcomes for early-stage cutaneous melanoma by offering more effective and less invasive methods. This approach has the potential to enhance both photothermal therapy (PTT) and Sentinel Lymph Node Biopsy (SLNB) procedures for melanoma patients. Methods: NIR-797-isothiocyanate was encapsulated in poly(D,L-lactide-co-glycolide) acid (PLGA) nanoparticles (NPs) using a two-step protocol, followed by thorough characterization, including assessing loading efficiency, fluorescence stability, and photothermal conversion. Biocompatibility and cellular uptake were tested in vitro on melanoma cells, while PTT assay, with real-time thermal monitoring, was performed in vivo on tumor-bearing mice under irradiation with an 808 nm laser. Finally, ex vivo fluorescence microscopy, histopathological assay, and TEM imaging were performed. Results: Our PLGA NPs, with a diameter of 270 nm, negative charge, and 60% NIR-797 loading efficiency, demonstrated excellent stability and fluorescence properties, as well as efficient light-to-heat conversion. In vitro studies confirmed their biocompatibility and cellular internalization. In vivo experiments demonstrated their efficacy as photothermal agents, inducing mild hyperthermia with temperatures reaching up to 43.8 °C. Ex vivo microscopy of tumor tissue confirmed persistent NIR fluorescence and uniform distribution of the NPs. Histopathological and TEM assays revealed early apoptosis, immune cell response, ultrastructural damage, and intracellular material debris resulting from combined NP treatment and irradiation. Additionally, TEM analyses of irradiated zone margins showed attenuated cellular damage, highlighting the precision and effectiveness of our targeted treatment approach. Conclusion: Specifically tailored for dual-modal NIR functionality, our NPs offer a novel approach in cancer PTT and real-time fluorescence monitoring, signaling a promising avenue toward clinical translation.

Comparison of manual versus automated thermal lid therapy with expression for meibomian gland dysfunction in patients with dry eye disease.

To compare two types of lipid expression procedures to treat dry eye disease. Standardized treatment and evaluation methods were used in patients treated with either manual thermoelectric lipid expression (MiBoFlo) or automated lipid expression (Lipiflow) of the Meibomian glands. This was a contemporaneous, non-randomized study of both treatment methods. Treatment was per the manufacturers' recommendation. The primary outcome included two types of dry eye questionnaires as well as objective analysis of ocular surface including tear break up time, Schirmer testing, Osmolarity, and fluorescein staining. Baseline characteristics analyzed included floppy lid, conjunctivochalasis and lagophthalmos. Statistical analysis was performed correcting for baseline factors such as age and co existing pathology using multivariable analysis. Both treatments improved the results of the OSDI and SPEED dry eye questionnaire results. Both treatments resulted in improvement of many objective findings including SPK, lissamine green staining and tear break up time with the MiBoFlo showing more improvement than Lipiflow. OSDI was more sensitive to improvement of symptoms than the SPEED questionnaire. Manual expression with MiBoFlo device resulted in statistically more improvement in questionnaire scores than did automated expression with Lipiflow. Negative prognostic factors for symptomatic improvement included blepharitis, autoimmune disease and ocular allergies. Thermal lid therapy along with mechanical expression of lipids from the meibomian glands successfully treats dry eye symptoms and signs. Manual therapy with MiBoFlo resulted in more subjective and objective improvement scores than automated therapy with the Lipiflow device.

Magnetic Hyperthermia in Glioblastoma Multiforme Treatment.

Glioblastoma multiforme (GBM) represents one of the most critical oncological diseases in neurological practice, being considered highly aggressive with a dismal prognosis. At a worldwide level, new therapeutic methods are continuously being researched. Magnetic hyperthermia (MHT) has been investigated for more than 30 years as a solution used as a single therapy or combined with others for glioma tumor assessment in preclinical and clinical studies. It is based on magnetic nanoparticles (MNPs) that are injected into the tumor, and, under the effect of an external alternating magnetic field, they produce heat with temperatures higher than 42 °C, which determines cancer cell death. It is well known that iron oxide nanoparticles have received FDA approval for anemia treatment and to be used as contrast substances in the medical imagining domain. Today, energetic, efficient MNPs are developed that are especially dedicated to MHT treatments. In this review, the subject's importance will be emphasized by specifying the number of patients with cancer worldwide, presenting the main features of GBM, and detailing the physical theory accompanying the MHT treatment. Then, synthesis routes for thermally efficient MNP manufacturing, strategies adopted in practice for increasing MHT heat performance, and significant in vitro and in vivo studies are presented. This review paper also includes combined cancer therapies, the main reasons for using these approaches with MHT, and important clinical studies on human subjects found in the literature. This review ends by describing the most critical challenges associated with MHT and future perspectives. It is concluded that MHT can be successfully and regularly applied as a treatment for GBM if specific improvements are made.

Evaluation of magnetic resonance thermometry performance during MR-guided hyperthermia treatment of soft-tissue sarcomas in the lower extremities and pelvis.

INTRODUCTION: This study evaluated the performance of magnetic resonance thermometry (MRT) during deep-regional hyperthermia (HT) in pelvic and lower-extremity soft-tissue sarcomas. MATERIALS AND METHODS: 17 pelvic (45 treatments) and 16 lower-extremity (42 treatments) patients underwent standard regional HT and chemotherapy. Pairs of double-echo gradient-echo scans were acquired during the MR protocol 1.4 s apart. For each pair, precision was quantified using phase data from both echoes ('dual-echo') or only one ('single-echo') in- or excluding body fat pixels in the field drift correction region of interest. The precision of each method was compared to that of the MRT approach using a built-in clinical software tool (SigmaVision). Accuracy was assessed in three lower-extremity patients (six treatments) using interstitial temperature probes. The Jaccard coefficient quantified pretreatment motion; receiver operating characteristic analysis assessed its predictability for acceptable precision (<1 °C) during HT. RESULTS: Compared to the built-in dual-echo approach, single-echo thermometry improved the mean temporal precision from 1.32 ± 0.40 °C to 1.07 ± 0.34 °C (pelvis) and from 0.99 ± 0.28 °C to 0.76 ± 0.23 °C (lower extremities). With body fat-based field drift correction, single-echo mean accuracy improved from 1.4 °C to 1.0 °C. Pretreatment bulk motion provided excellent precision prediction with an area under the curve of 0.80-0.86 (pelvis) and 0.81-0.83 (lower extremities), compared to gastrointestinal air motion (0.52-0.58). CONCLUSION: Single-echo MRT exhibited better precision than dual-echo MRT. Body fat-based field-drift correction significantly improved MRT accuracy. Pretreatment bulk motion showed improved prediction of acceptable MRT temporal precision over gastrointestinal air motion.