Laser-induced Thermotherapy Research Articles

LASER-INDUCED THERMOTHERAPY OF COLLOIDAL CYSTIC THYROID NODULES: THE EFFICACY AND SAFETY

The authors studied the treatment results of application of the laser-induced thermotherapy method in 414 patients with nodular colloid goiter. Dynamics of the nodule sizes was estimated in 298 (72, 0%) patients. Dynamics of thyroid status was assessed in 132 (31, 8%) patients. The average size was reduced more than 60% among the nodules with the volume up to 1 cm³. In case of nodules with the volume more than 8 cm³, the average size was decreased more than 40%. The majority of nodules with the volume of 1 cm³ were reduced more than 50% (45 out of 80), other nodules 19 (23,8%) were decreased more than 75% and 12 nodules completely vanished. The nodules with the volume of 1-2 cm³ were reduced more than half of them on 50% (41 out of 71), the rest of the nodules - on 75% and more than fifth part of them. At the same time, there wasn’t noted the decrease more than 75% in the nodules with the volume of 4 cm ³. However, the volume decrease was observed among such nodules, the majority of the nodules were reduced more than a quarter. During this procedure the patients 305 (73,7%) felt some discomfort and low-intensive pain in area of manipulation. The pains were completely arrested in 289 patients in the end of this procedure, but aching continued in the case of 16 patients for more long time (from 12 to 24 hours). There was noted the temperature rise up to the level of low grade fever in 11 (2,7%) patients during 12-24 hours. Complications of laser-induced thermotherapy had 21 (5,1%) patients. An intracutaneous unstrained haematoma was defined in 15 patients in injection area. There was noted a skin burn in spot of the injection in 5 (1,2%) patients. Paresis of the vocal ligament took place in one patient (0,2%), but it was treated in phonopedist and mobility of the vocal ligament was restored. Hyperthyroidism was caused in two patients and, according to the authors, it could be associated with drug intake of “сordaron”.

EGALLOHIT GEL IN PATIENTS WITH LASER-INDUCED THERMOTHERAPY OF SUPERFICIAL AND MICRONODULAR BASALIOMA

Background: In basalioma, facial skin is frequent- E-mail: mmacosmetology@mail.ru ly affected. Thus, good cosmetological effect of treatment and anti-tumor efficacy are both important. Optimal approach includes prevention of pathological scarring. In many cases, preventive measures ensure normal scarring even after invasive methods of treatment. Aim: To assess efficacy and safety of Egallohit gel and its effects on scarring in patients with laser-induced thermotherapy (LITT) of basalioma. Materials and methods: 42 patients with superficial and micronodular basaliomas were included. LITT is a new highly effective and less invasive method providing satisfactory cosmetic results. Comprehensive treatment involved LITT (1 or 2 cycles) with subsequent application of Egallohit gel (up to 30 days after the intervention). Results: After the first LITT, clinical cure of basalioma was demonstrated in 41 (97.6%) patients. In one patient with superficial basalioma clinical cure was achieved after the second cycle of LITT. After epithelization of the tumor site, excellent and good clinical result was observed in 15 (35.7%) and 22 (52.5%) patients, respectively (satisfactory results were found only in 5 cases (11,8%), p<0,05). According to the Likert scale scores, 40 patients (95.2%) were very satisfied and 2 patients (4.8%) were satisfied with the treatment. Conclusion: Adding Egallohit after LITT in patients with basaliomas resulted in reduction of connective tissue growth in the lesions, promoted scar tissue resolution and surface smoothening (especially during scar formation), inhibited hyperemia and pigmentation and improved elasticity and displaceability of surrounding tissues.

Image-guided high-dose-rate brachytherapy of malignancies in various inner organs - technique, indications, and perspectives.

In the last few years, minimally invasive tumor ablation performed by interventional radiologists has gained increasing relevance in oncologic patient care. Limitations of thermal ablation techniques such as radiofrequency ablation (RFA), microwave ablation (MWA), and laser-induced thermotherapy (LITT), including large tumor size, cooling effects of adjacent vessels, and tumor location near thermosensitive structures, have led to the development of image-guided high-dose-rate (HDR) brachytherapy, especially for the treatment of liver malignancies. This article reviews technical properties of image-guided brachytherapy, indications and its current clinical role in multimodal cancer treatment. Furthermore, perspectives of this novel therapy option will be discussed.

New Techniques in MRI-Fluid-attenuated Inversion Recovery (FLAIR) Imaging, Diffusion Tensor Imaging (DTI), and MRI-guided Laser-induced Thermotherapy (LITT) for Brain Lesions.

New Techniques in MRI-Fluid-attenuated Inversion Recovery (FLAIR) Imaging, Diffusion Tensor Imaging (DTI), and MRI-guided Laser-induced Thermotherapy (LITT) for Brain Lesions.

Internal structuring of silica glass fibers: Requirements for scattered light applicators for the usability in medicine

Abstract Background: Diffuser fibers have been used for some time in the fields of laser-induced thermotherapy and photodynamic therapy. For their applicability the breaking strength, the thermostability and a homogeneous radiation profile are of great importance. Flexible applicators offer special benefits because they introduce a totally new range of application possibilities. Objective: The aim of the presented investigations was to develop a totally new flexible diffuser fiber generation which can be produced cheaper and without the use of any further materials. For this purpose it was proposed to induce scattering micro dots directly into silica fibers by generating a local change of the refractive index in the core of the optical fiber. The resulting diffuser was expected to create a homogeneous radiation profile containing at least 80% of the light coupled into the optical fiber, i.e. less than 20% prograde (forward) emission. Materials and methods: On the basis of former research results, scattering micro dots were induced linearly into the core of an optical silica fiber through a multiple photon process using a femtosecond laser. In addition to the macroscopic optical control by means of a microscope, the form of the radiation profile was examined as well as the non-scattered forward emission which depends on a variety of influencing factors. The processing was optimized according to the observations made. The thermostability of the developed prototypes was assessed by using a thermocamera, and the minimal bending radius was determined. Finally the prototypes were tested and validated ex vivo using porcine liver. Results: An influence of the processing power, the number and radial position of the scattering micro dots as well as the therapeutic coupled-in wavelength onto the form of the radiation profile and the non-scattered forward emission was determined. Both the form of the radiation profile and the prograde emission were found to be independent of the therapeutic laser power coupled into the fiber. The developed prototype had a nearly homogeneous radiation profile, a forward emission of 12.8±2.1% in average, and a minimum bending radius of 31±6 mm. Conclusion: The non-scattered forward emission of the developed diffusers was within the objective of below 20% and the radiation profile was very nearly homogeneous. In order to improve the reproducibility of the production process, an improved fixation apparatus needs to be developed.

Лечение узлового эутиреоидного зоба лазериндуцированной интерстициальной термотерапией

Лечение узлового эутиреоидного зоба лазериндуцированной интерстициальной термотерапией

Four years of experience of minimally invasive treatment of benign thyroid nodule

With the use of minimally invasive techniques (MIM) treated 489 patients with cystic-colloid nodes. Laser-induced thermotherapy (LITT) — 371 patient, Ethanol destruction of ED — 54 patients, 63 — combined technique (KombiLITT). Dynamics of node size was assessed in 356 patients (72.8%). LITT — 252 patients, ED — 50 patients KombiLITT — 52 patients. LITT used in the treatment of solid structure nodes. Additional nodes up to 1 cm 3 after LITT large part diminished by more than 50% (43 of 76). Additional nodes 1—2 cm 3 also decreased more than half by more than 50% (39 of 67). Among nodules greater than 4 cm 3 was not a single site that would reduce in volume by more than 75%. However, most of them decreased by more than 25%. The algorithm of differential treatment of cystic nodes. ED performed in 54 patients with cystic destruction of a site more than 70%. Marked decrease in the average volume at 4.68 ± 2.25 cm 3 to 1.15 ± 0.9 cm 3 . KombiLITT performed in 63 patients with cystic cavity 20 to 70%. Volume units decreased at 7.98 ± 4.56 cm 3 to 1.87 ± 0.9 cm 3 . LITT performed in 30 patients with major nodes and cystic cavities less than 20% of the site. Marked decrease in the volume of units at 2.89 ± 1.25 cm 3 and 1.42 ± 0.8 cm 3 . LITT held 31 patients with small cystic nodes to 1 cm 3 . Marked decrease in size at 0.69 ± 0.23 cm 3 to 0.29 ± 0.12 cm 3 . It has been shown that changes in thyroid status after MIM operations does not occur.

Neoadjuvant TACE before laser induced thermotherapy (LITT) in the treatment of non-colorectal non-breast cancer liver metastases: Feasibility and survival rates

PurposeTo evaluate safety, feasibility and overall survival rates for transarterial chemoembolization (TACE) alone or combined with MR-guided laser-induced-thermotherapy (LITT) in liver metastases of non-colorectal and non-breast cancer origin. Methods and materialsIncluded were patients with unresectable non-colorectal non-breast cancer liver metastases with progression under systemic chemotherapy. Excluded were patients with Karnofsky score ≤70, respiratory, renal and cardiovascular failure, and general TACE contraindications. TACE using Mitomycin alone, Mitomycin–Gemcitabine or Mitomycin–Gemcitabine–Cisplatin was performed to all patients. After TACE 146 metastases were ablated with MR-guided LITT. To be eligible for LITT metastases should be <5cm in size and ≤5 in number. Tumor response was evaluated using MRI according to RECIST. Survival was evaluated using Kaplan–Meier analysis. ResultsA total of 110 patients (mean age 59.2 years) with 371 metastases received TACE (mean 5.4 sessions/patient, n=110) with 76 (69%) receiving LITT (mean 1.6 session/patient) afterwards. TACE resulted in a mean decrease of mean maximum diameter of 52%±26.6 and volume change of −68.5%±22.9 in the 25 patients (23%) with partial response. Stable disease (n=59, 54%). Progressive disease (n=26, 23%). The RECIST outcome after LITT showed complete response (n=13, 17%), partial response (n=1, 1%), stable situation (n=41, 54%) and progressive disease (n=21, 28%). The mean time to progression (TTP) was 8.6 months. Median survival of all patients was 21.1 months. ConclusionTACE with different protocols alone and in combination with LITT is a feasible palliative treatment option resulting in a median survival of 21.1 months for unresectable liver metastases of non-colorectal and non-breast cancer origin.

Thermal ablation of liver metastases from colorectal cancer: radiofrequency, microwave and laser ablation therapies.

Surgery is currently considered the treatment of choice for patients with colorectal cancer liver metastases (CRLM) when resectable. The majority of these patients can also benefit from systemic chemotherapy. Recently, local or regional therapies such as thermal ablations have been used with acceptable outcomes. We searched the medical literature to identify studies and reviews relevant to radiofrequency (RF) ablation, microwave (MW) ablation and laser-induced thermotherapy (LITT) in terms of local progression, survival indexes and major complications in patients with CRLM. Reviewed literature showed a local progression rate between 2.8 and 29.7 % of RF-ablated liver lesions at 12-49 months follow-up, 2.7-12.5 % of MW ablated lesions at 5-19 months follow-up and 5.2 % of lesions treated with LITT at 6-month follow-up. Major complications were observed in 4-33 % of patients treated with RF ablation, 0-19 % of patients treated with MW ablation and 0.1-3.5 % of lesions treated with LITT. Although not significantly different, the mean of 1-, 3- and 5-year survival rates for RF-, MW- and laser ablated lesions was (92.6, 44.7, 31.1 %), (79, 38.6, 21 %) and (94.2, 61.5, 29.2 %), respectively. The median survival in these methods was 33.2, 29.5 and 33.7 months, respectively. Thermal ablation may be an appropriate alternative in patients with CRLM who have inoperable liver lesions or have operable lesions as an adjunct to resection. However, further competitive evaluation should clarify the efficacy and priority of these therapies in patients with colorectal cancer liver metastases.

Change in refractive index of muscle tissue during laser-induced interstitial thermotherapy

This paper presents a long-period fiber-grating (LPG) based Michelson interferometric refractometry to monitor the change in refractive index of porcine muscle during laser-induced interstitial thermotherapy (LITT). As the wavelength of RI interferometer alters with the change in refractive index around the probe, the LPG based refractometry is combined with LITT system to measure the change in refractive index of porcine muscle when irradiated by laser. The experimental results show the denaturation of tissue alters the refractive index significantly and the LPG sensor can be applied to monitor the tissue state during the LITT.

Minimally invasive surgery colloidal cystic thyroid nodules

An analysis of the use of minimally invasive interventions - laser-induced thermotherapy (LITT), ethanol destruction (ED) under ultrasound guidance, a combination of these methods in the treatment of сystic-col- loidal nodes (CCN) of thyroid nodules in 120 patients. ED carried out in 31 patients with cystic destruction of a site of more than 70%. Marked decrease in the average volume with 4.68 ± 2.25 cm3 to 1.15 ± 0.9 cm3. In 4 patients remained cystic cavity of small size, which required a combination of LITT (CombiLITT). Nine patients underwent LITT solid residue of more than 1 cm3. The average size of nodules within 6 months after the primary surgery was 0.9 ± 0.3 cm3. СombiLITT performed in 42 patients with cystic cavity from 20 to 70%. The volume of units decreased from 7.98 ± 4.56 to 1.87 ± 0.9 cm3. After 3 months, 11 patients with the size of a solid residue of more than 1 cm3 held LITT. All of them when viewed after 3 months observed decrease of more than 50%. LITT performed 23 patients with major nodes and cystic cavities less than 20% of the node. Marked decrease in the amount of nodes with 2.89 ± 1.25 cm3 to 1.42 ± 0.8 cm3. Retesting LITT took 2 patients. After 6 months, the average amount of units was 0.7 ± 0.2 cm3 LITT conducted in 24 patients with small cystic nodes to 1 cm3. Marked decrease in size from 0.69 ± 0.23 cm3 to 0.29 ± 0.12 cm3. Varied selection of minimally inva- sive treatment of CCN is effective and in most cases, to achieve reduction of the size of nodes.

Evaluation of MRI T1-based treatment monitoring during laser-induced thermotherapy of liver metastases for necrotic size prediction

Purpose: The aim of this study was to evaluate the accuracy of real-time magnetic resonance imaging (MRI) T1-based treatment monitoring for predicting volume of lesions induced by laser-induced thermotherapy (LITT) of liver metastases.Materials and methods: This prospective study was approved by the institutional review board and informed consent from all included patients was obtained. In 151 patients, 237 liver metastases were ablated during 372 LITT procedures. 1.5T MRI treatment monitoring was performed based on longitudinal relaxation time (T1) using fast low-angle shot (FLASH) sequences. Patients underwent additional contrast-enhanced MRI directly after LITT, 24 h after the procedure and during follow-up at 3, 6 and 12 months. The amount of energy necessary to induce a defined necrotic area was investigated within the various liver segments.Results: The total amount of energy applied during LITT varied from 6.12–225.32 kJ (mean 48.96 kJ). Ablation in liver segments 5 (2.12 kJ/cm3) and 8 (2.16 kJ/cm3) required the highest energy. The overall pre-ablative metastasis volume ranged from 0.5–51.94 cm3 (mean 1.99 cm3, SD 25.49 cm3) while the volume measured in the last available T1 image varied from 0.78–120 cm3 (mean 26.25 cm3, SD 25.66 cm3). Volumes measured via MRI T1-based treatment monitoring showed a stronger correlation with necrosis 24 h after LITT (r = 0.933, p < 0.001) than contrast-enhanced MRI directly after the procedure (r = 0.888, p < 0.001).Conclusions: Real-time MRI T1-based treatment monitoring during LITT of liver metastases allows for precise estimation of the resulting lesion volume and improves control of the energy necessary during ablation.

Magnetic Resonance Temperature Imaging of Laser-Induced Thermotherapy: Assessment of Fast Sequences in Ex Vivo Porcine Liver

To evaluate magnetic resonance sequences for T(1) and proton resonance frequency (PRF) thermometry during laser-induced thermotherapy (LITT) in liver tissue. During LITT (1064 nm; 30 W; 3-cm diffuser; 2-3 min) in ex vivo porcine liver, temperature was measured (25-70°C) utilizing a fiberoptic thermometer and MRI was performed with a 1.5-T scanner through the following sequences: segmented echo planar imaging (seg-EPI) for the PRF method; fast low-angle shot (FLASH), inversion-recovery turbo FLASH (IRTF), saturation-recovery turbo FLASH (SRTF) and true-fast imaging (TRUFI) for the T(1) method. Phase angle and signal amplitude (regarding PRF/T(1)) was recorded in regions of interest, on images under fiberoptic probe tips. Sequences' thermal coefficients were determined by calibrating phase angle and signal amplitude against temperature and subsequently validated. Coefficients of -0.0089 ± 0.0003 ppm °C(-1) (seg-EPI) and -0.917 ± 0.046, -1.166 ± 0.058, -1.038 ± 0.054 and -1.443 ± 0.118°C(-1) (FLASH, IRTF, SRTF and TRUFI, respectively) were obtained. Precisions of 0.71, 1.34, 2.07, 2.44 and 3.21°C and, through Bland-Altman analysis, accuracies of -0.67, 0.79, 1.65, 1.57 and 2.13°C (seg-EPI, FLASH, IRTF, SRTF and TRUFI, respectively) were determined. The PRF method with seg-EPI sequence is preferred for thermometry during LITT owing to higher precision and accuracy. Among T(1)-method sequences, FLASH showed higher accuracy and robustness.

Temperature monitoring and lesion volume estimation during double-applicator laser-induced thermotherapy in ex vivo swine pancreas: a preliminary study

Tissue temperature distribution plays a crucial role in the outcome of laser-induced thermotherapy (LITT), a technique employed for neoplasias removal. Since recent studies proposed LITT for pancreatic tumors treatment, assessment of temperature and of its effects around the laser applicator could be useful to define optimal laser settings. The aims of this work are temperature monitoring and measurement of ablated tissue volume in an ex vivo porcine pancreas undergoing double-applicator LITT. A three-dimensional numerical model is implemented to predict temperature rise and volumes of ablated tissue in treated pancreas. Experiments are performed to validate the model, with two modalities: (1) 12-fiber Bragg grating sensors are adopted to monitor the heating and cooling during LITT at several distances from the applicators tip, and (2) 1.5-T MR imaging is used to estimate the ablated volume. Experimental data agree with theoretical ones: at 2mm from both applicators tips, the maximum temperature increase is approximately 60°C downward from the tips, while it increases of about 40°C and 30°C, respectively, at the level and upward from the tips. This behavior occurs also at other distances, proving that the tissue downward from the tip is mostly heated. Furthermore, the estimated volume with MRI agrees with theoretical one (i.d., 0.91 ± 0.09 vs. 0.95cm(3)). The encouraging results indicate that the model could be a suitable tool to choose the optimal laser settings, in order to control the volume of ablated tissue.

Magnetic Resonance–Guided Laser-Induced Interstitial Thermotherapy of Breast Cancer Liver Metastases and Other Noncolorectal Cancer Liver Metastases

The purpose of this study was the evaluation of prognostic factors for long-term survival and progression-free survival (PFS) after treatment of noncolorectal cancer liver metastases through MR-guided laser-induced thermotherapy (LITT). We included 401 patients (mean age, 57.3 years) with liver metastases from different primary tumors who were treated with LITT. Long-term survival and progression-free-survival rates were evaluated using the Kaplan-Meier method. A Cox regression model tested different parameters that could be of prognostic value. The tested prognostic factors were as follows: the location of primary tumor, TNM classification, extrahepatic metastases, hepatic resection or neoadjuvant transarterial chemoembolization or systemic chemotherapy before LITT, the number of initial metastases, the volume of metastases, and the quotient of total volumes of metastases and necroses per patient. The median survival was 37.6 months starting from the date of LITT. The 1-, 2-, 3-, 4-, and 5-year survival rates were 86.5%, 67.2%, 51.9%, 39.9%, and 33.4%, respectively. The median PFS was 12.2 months. The 1-, 2-, 3-, 4-, and 5-year PFS rates were 50.6%, 33.8%, 26%, 20.4%, and 17%, respectively. The initial number of metastases, the volumes of metastases, and the quotient of the volumes of metastases and necroses influenced the long-term survival and the PFS. Laser-induced thermotherapy is a minimally invasive method in the treatment of hepatic metastases of noncolorectal cancer, and it shows good results in long-term survival and PFS. The initial number of metastases and their volume are the most important prognostic factors. The status of the lymph nodes, the existence of other extrahepatic metastases, the location of the primary tumor, and different neoadjuvant therapies are of nonprognostic value.

Stereotactic laser induced thermotherapy (LITT): a novel treatment for brain lesions regrowing after radiosurgery

Since the inception of radiosurgery, the management of brain metastases has become a common problem for neurosurgeons. Although the use of stereotactic radiosurgery and/or whole brain radiation therapy serves to control the majority of disease burden, patients who survive longer than 6-8 months sometimes face the problem of symptomatic radiographically regrowing lesions with few treatment options. Here we investigate the feasibility of use of MRI-guided stereotactic laser induced thermotherapy (LITT) as a novel treatment option for these lesions. Six patients who had previously undergone gamma knife stereotactic radiosurgery for brain metastases were selected. All patients had an initial favorable response to radiosurgery but subsequently developed regrowth of at least one lesion associated with recurrent edema and progressive neurological symptoms requiring ongoing steroids for symptom control. All lesions were evaluated for craniotomy, but were deemed unresectable due to deep location or patient's comorbidities. Stereotactic biopsies were performed prior to the thermotherapy procedure in all cases. LITT was performed using the Visualase system and follow-up MRI imaging was used to determine treatment response. In all six patients biopsy results were negative for tumor and consistent with adverse radiation effects also known as radiation necrosis. Patients tolerated the procedure well and were discharged from the hospital within 48 h of the procedure. In 4/6 cases there was durable improvement of neurological symptoms until death. In all cases steroids were weaned off within 2 months. One patient died from systemic causes related to his cancer a month after the procedure. One patient had regrowth of the lesion 3 months after the procedure and required re-initiation of steroids and standard craniotomy for surgical resection. There were no complications directly related to the thermocoagulation procedure. Stereotactic laser induced thermotherapy is a feasible alternative for the treatment of symptomatic regrowing metastatic lesions after radiosurgery. The procedure carries minimal morbidity and, in this small series, shows some effectiveness in the symptomatic relief of edema and neurological symptoms paralleled by radiographic lesional control. Further studies are necessary to elucidate the safety of this technology.

Temperature imaging of laser-induced thermotherapy (LITT) by MRI: evaluation of different sequences in phantom

The purpose of this study was to evaluate magnetic resonance (MR) temperature imaging of the laser-induced thermotherapy (LITT) comparing the proton resonance frequency (PRF) and T 1 thermometry methods. LITT was applied to a liver-mimicking acrylamide gel phantom. Temperature rise up to 70 °C was measured using a MR-compatible fiber-optic thermometer. MR imaging was performed by a 1.5-T scanner utilizing fast gradient echo sequences including a segmented echo planar imaging (seg-EPI) sequence for PRF and the following sequences for T 1 method: fast low-angle shot (FLASH), inversion recovery turbo flash (IRTF), saturation recovery turbo flash (SRTF), and true fast imaging (TRUFI). Temperature-induced change of the pixel values in circular regions of interest, selected on images under the temperature probe tip, was recorded. For each sequence, a calibration constant could be determined to be -0.0088 ± 0.0002 ppm °C(-1) (EPI), -1.15 ± 0.03 °C(-1) (FLASH), -1.49 ± 0.03 °C(-1) (IRTF), -1.21 ± 0.03 °C(-1) (SRTF), and -2.52 ± 0.12 °C(-1) (TRUFI). These constants were evaluated in further LITT experiments in phantom comparing the calculated temperatures with the fiber optic-measured ones; temperature precisions of 0.60 °C (EPI), 0.81 °C (FLASH), 1.85 °C (IRTF), 1.95 °C (SRTF), and 3.36 °C (TRUFI) were obtained. Furthermore, performing the Bland-Altman analysis, temperature accuracy was determined to be 0.23 °C (EPI), 0.31 °C (FLASH), 1.66 °C (IRTF), 1.19 °C (SRTF), and 3.20 °C (TRUFI). In conclusion, the seg-EPI sequence was found to be more convenient for MR temperature imaging of LITT due to its relatively high precision and accuracy. Among the T 1 method sequences, FLASH showed the highest accuracy and robustness.

Laserinduced thermotherapy application in treatment benign nodular thyroid pathology

Results of the treatment laserinduced thermotherapy (LITT) of 107 patients with benign thyroid nodules. The average volume of nodes before and after treatment was reduced from 5.0 cm 3 to 2.8 cm 3 (44%). Of nod ules up to 1 cm 3 average volume decreased by more than 60%. Among large nodules larger than 8 cm 3 aver age decreased only slightly more than 40%. Among the nodes up to 1 cm 3 after LITT most decreased by more than 50% (19 of 33), 8 of them (24.2%) decreased by more than 75%, 6 (18.3%) nodes have disap peared completely. Among the nodes of 2.1 cm 3, more than half also fell by more than 50% (17 of 29), of which more than 75% – 6 knots (20.7%). Of nodules more than 4 cm 3 was not a single node, which would decrease in volume by more than 75%. However, most of them fell by more than 25%. There was a statisti cally significant difference according to volume reduction of the number of node points of the laser action. Three patients (2.8%) had a small burn the skin at the puncture needle. LITT method benign thyroid nodules is high, because overwhelmingly majority of cases leads to either the disappearance or significant reduction of thyroid nodules.

Vaccinia virus-mediated melanin production allows MR and optoacoustic deep tissue imaging and laser-induced thermotherapy of cancer

We reported earlier the delivery of antiangiogenic single chain antibodies by using oncolytic vaccinia virus strains to enhance their therapeutic efficacy. Here, we provide evidence that gene-evoked production of melanin can be used as a therapeutic and diagnostic mediator, as exemplified by insertion of only one or two genes into the genome of an oncolytic vaccinia virus strain. We found that produced melanin is an excellent reporter for optical imaging without addition of substrate. Melanin production also facilitated deep tissue optoacoustic imaging as well as MRI. In addition, melanin was shown to be a suitable target for laser-induced thermotherapy and enhanced oncolytic viral therapy. In conclusion, melanin as a mediator for thermotherapy and reporter for different imaging modalities may soon become a versatile alternative to replace fluorescent proteins also in other biological systems. After ongoing extensive preclinical studies, melanin overproducing oncolytic virus strains might be used in clinical trials in patients with cancer.

Investigation of Sub-100 nm Gold Nanoparticles for Laser-Induced Thermotherapy of Cancer.

Specialized gold nanostructures are of interest for the development of alternative treatment methods in medicine. Photothermal therapy combined with gene therapy that supports hyperthermia is proposed as a novel multimodal treatment method for prostate cancer. In this work, photothermal therapy using small (<100 nm) gold nanoparticles and near-infrared (NIR) laser irradiation combined with gene therapy targeting heat shock protein (HSP) 27 was investigated. A series of nanoparticles: nanoshells, nanorods, core-corona nanoparticles and hollow nanoshells, were synthesized and examined to compare their properties and suitability as photothermal agents. In vitro cellular uptake studies of the nanoparticles into prostate cancer cell lines were performed using light scattering microscopy to provide three-dimensional (3D) imaging. Small gold nanoshells (40 nm) displayed the greatest cellular uptake of the nanoparticles studied and were used in photothermal studies. Photothermal treatment of the cancer cell lines with laser irradiation at 800 nm at 4 W on a spot size of 4 mm (FWHM) for 6 or 10 min resulted in an increase in temperature of ~12 °C and decrease in cell viability of up to 70%. However, in vitro studies combining photothermal therapy with gene therapy targeting HSP27 did not result in additional sensitization of the prostate cancer cells to hyperthermia.