Far-infrared radiation alleviates cisplatin-induced vascular damage and impaired circulation via activation of HIF-1α.

Severe vascular damage and complications are often observed in cancer patients during treatment with chemotherapeutic drugs such as cisplatin. Thus, development of potential options to ameliorate the vascular side effects is urgently needed. In this study, the effects and the underlying mechanisms of far-infrared radiation (FIR) on cisplatin-induced vascular injury and endothelial cytotoxicity/dysfunction in mice and human umbilical vein endothelial cells (HUVECs) were investigated. An important finding is that the severe vascular stenosis and poor blood flow seen in cisplatin-treated mice were greatly mitigated by FIR irradiation (30 minutes/day) for 1-3 days. Moreover, FIR markedly increased the levels of phosphorylation of PI3K and Akt, and VEGF secretion, as well as the expression and the activity of hypoxia-inducible factor 1α (HIF-1α) in cisplatin-treated HUVECs in a promyelocytic leukemia zinc finger protein (PLZF)-dependent manner. However, FIR-stimulated endothelial angiogenesis and VEGF release were significantly diminished by transfection with HIF-1α siRNA. We also confirmed that HIF-1α, PI3K, and PLZF contribute to the inhibitory effect of FIR on cisplatin-induced apoptosis in HUVECs. Notably, FIR did not affect the anticancer activity and the HIF-1α/VEGF cascade in cisplatin-treated cancer cells under normoxic or hypoxic condition, indicating that the actions of FIR may specifically target endothelial cells. It is the first study to demonstrate that FIR effectively attenuates cisplatin-induced vascular damage and impaired angiogenesis through activation of HIF-1α-dependent processes via regulation of PLZF and PI3K/Akt. Taken together, cotreatment with the noninvasive and easily performed FIR has a therapeutic potential to prevent the pathogenesis of vascular complications in cancer patients during cisplatin treatment.

Multiwavelength laser treatment of venous lakes.

BACKGROUND: Venous lakes (VLs) are common benign ectasias in the upper dermis, usually observed in older people. Different treatment strategies have been described as useful, such as cryosurgery, excision, and various types of laser. OBJECTIVE: We report our experiences using a multiwavelength laser, which has not been previously described. PATIENTS AND METHODS: Thirty-nine VLs in 30 patients were treated. Treatment with 595-nm pulsed-dye laser was conducted at 20 ms and 10 J/cm(2), followed by 1,064-nm neodymium-doped yttrium aluminum garnet laser at 20 ms and 70 J/cm(2). RESULTS: Complete resolution was observed in 38 lesions (95%). No complications after treatment were noted. One case developed a small scar. CONCLUSIONS: Multiwavelentgh laser (595 nm; 1,064 nm) provides a safe, fast, and effective option in the treatment of VLs.

Clinical experience in the treatment of different vascular lesions using a neodymium-doped yttrium aluminum garnet laser.

BACKGROUND: A neodymium-doped yttrium aluminum garnet (Nd:YAG) laser has been used with good results for the treatment of various vascular lesions. OBJECTIVE: To report our experience with a variable long-pulsed Nd:YAG laser for the treatment of different vascular lesions. MATERIALS AND METHODS: One hundred ten patients with different vascular skin lesions were included. Patients were examined before the treatment; 1 week after each treatment session; and 1, 2, and 3 months after the last treatment session. Improvement was judged according to clinical examination of the patients and by comparing pre- and post-treatment photographs. Results were graded in four groups using percentage resolution (0-25%, 26-50%, 51-75%, and 76-100%. RESULTS: One hundred five patients (19 port wine stains, 48 telangiectasias, 25 hemangiomas, and 13 other vascular lesions) completed the study; 71.5% of patients showed greater than 50% improvement. Good to excellent (more than 50%) results were achieved in 63.2% of patients with port wine stain, 80.0% of patients with hemangioma, 66.7% of patients with telangiectasia, and 84.6% of patients with other vascular lesions; 71.5% of all patients were very satisfied or satisfied with the results. CONCLUSION: A variable long-pulsed Nd:YAG laser was found to be effective in the treatment of different vascular lesions ranging from easy to difficult to treat. The authors have indicated no significant interest with commercial supporters.

Diagnosis and interventional radiological treatment of vascular and biliary complications after liver transplantation in children with biliary atresia.

OBJECTIVE: Early diagnosis and appropriate management of vascular and biliary complications after living donor liver transplantation (LDLT) result in longer survival. We report our institutional experience regarding radiological management of these complications among patients with biliary atresia (BA) who underwent LDLT. METHODS: We analyzed the records of 116 children. All patients underwent Doppler ultrasound (US) at operation, daily for the first 2 postoperative weeks, and when necessary thereafter. After primary evaluation using US, the definite diagnosis of postoperative complication was confirmed using computed tomography, magnetic resonance imaging, and/or operation. RESULTS: There were 61 boys and 55 girls. The overall mean age was 2.69 years. The overall mean preoperative weight and height were 13.06 kg and 83.79 cm, respectively. There were 28 (24.13%) biliary and vascular complications. These were cases of biliary stricture (n = 5), bile leakage (n = 3), hepatic artery stenosis (n = 6), hepatic vein stenosis (n = 4), and portal vein thrombosis (n = 17). The diagnostic accuracy of US in detecting biliary complication, hepatic artery stenosis, hepatic venous stenosis, and portal vein thrombosis was 95.69%, 97.41%, 100%, and 100%, respectively. US in combination with multiple imaging modalities and clinical suspicion resulted in 100% diagnostic accuracy. Percutaneous transhepatic cholangiography, thrombolysis, balloon angioplasty, and stent placement were performed for the complications noted. There was an early mortality due to multiple-organ failure after failed radiological invention and subsequent surgical management. CONCLUSIONS: Doppler US is accurate in detecting postoperative complications after pediatric LDLT for BA. Radiological interventions for vascular and biliary complications are effective and safe alternatives to reconstructive surgery.

Radiation therapy for the treatment of benign vascular, skeletal and soft tissue diseases.

The concept of radiation therapy for the treatment of benign diseases refers to the use of moderate to high-energy ionising radiation as part of the treatment of non-malignant, but not necessarily harmless, diseases. The usefulness of radiation therapy, based on the anti-inflammatory properties of ionising radiation, has long been known. Apart from the treatment of intracranial benign tumours, such as meningiomas and neurinomas, the prevention of cardiovascular restenosis or treatment of skeletal degenerative diseases are, without doubt, the main fields of action for radiation therapy in benign conditions. Nonetheless, many other non-cancer entities may benefit from ionising radiation therapy treatment. The purpose of this review is to highlight and update indications for treatment with radiation therapy in benign conditions, focusing on skeletal degenerative processes, vascular conditions and soft tissue diseases.

Intraluminal Brachytherapy Using a Self-Expandable Stent Loaded With Linear Iodine-125 Seeds in a Patient With Reiterative Recurrence of Cancer-Associated Vein Obstruction: A Case Report With 3 Months of Follow-Up.

Cancer-associated vein obstruction (CAVO) is a common complication in oncological patients, but the effective therapeutic options are scant. We report a patient with reiterative recurrent CAVO who was successfully treated with intraluminal brachytherapy using a self-expandable stent loaded with linear radioactive iodine-125 seeds (RIS) strand. During follow-up, her clinical symptoms were well improved. Three-month imaging follow-up revealed satisfactory patency of the iliofemoral vein, and the stents combined with RIS strands performed well. No serious complications associated with the implantation of stent and RIS strands were documented in any of the sessions. Intraluminal brachytherapy using a self-expandable stent loaded with linear RIS may be a safe and effective option for CAVO as long as it includes not only blood flow restoration but also brachytherapy administration for cancer.

Optimization of intravascular brachytherapy treatment planning in peripheral arteries.

This work deals with the treatment planning optimization for intravascular brachytherapy (IVB) in peripheral arteries. The objective is both to quantitatively study the validity of different hypotheses required for a reliable application of the treatment with current techniques, and to contribute to the definition and the specification of a new optimized procedure taking into account the actual patient's vessel geometry. The detection of vascular luminal surface was performed by an image analysis process, i.e., virtual active navigation, applied to standard CT data. Dose distribution was calculated according to the formalism proposed and recommended by the AAPM in TG43 and TG60. A method combining simulated annealing and BFGS algorithms was applied to optimize the parameters associated with the dwell points such as their number, positions, and dwell times. Dose-surface histogram (DSH) was used to evaluate the dose distribution results. Four levels of accuracy in target surface description were tested. The application of this optimization method to four different CT data sets including patient data, phantom and animal models showed that the treatment plan can be improved when the actual vessel geometry has been taken into account.

Beta dosimetry with microMOSFETs for endovascular brachytherapy.

The aim of this study was to investigate if microMOSFETs are suitable for the dosimetry and quality assurance of beta sources. The microMOSFET dosimeters have been tested for their angular dependence in a 6 MeV electron beam. The dose rate dependence was measured with an iridium-192 afterloading source. By varying the source-to-surface distance (SSD) in a 12 MeV electron beam the dose rate dependence in an electron beam was also investigated. To measure a depth dose curve the dose rate at 2, 5, 8 and 12 mm distance from the beta source train axis was determined with the OPTIDOS and the microMOSFET detector. A comparison between the two detector types shows that the microMOSFET is suitable for quality assurance of beta sources for endovascular brachytherapy (EVBT). The homogeneity of the source is checked by measurements at five points (for the 60 mm source at 10, 20, 30, 40 and 50 mm) along the source train. The microMOSFET was then used to evaluate the influence of a common stent type (single layer stainless steel) on the dose distribution in water. The stent led to a dose inhomogeneity of +/-8.5%. Additionally the percentage depth dose curves with and without a stent were compared. The depth dose curves show good agreement which means that the stent does not change the beta spectrum significantly.

Irradiation in the setting of collagen vascular disease: acute and late complications.

PURPOSE: Based on reports of greater toxicity from radiation therapy, collagen vascular diseases (CVDs) have been considered a contraindication to irradiation. We assessed the complications of radiation therapy in patients with CVD. PATIENTS AND METHODS: A total of 209 patients with documented CVD were irradiated between 1960 and 1995. One hundred thirty-one had rheumatoid arthritis (RA), 25 had systemic lupus erythematosus (SLE); 17 had polymyositis or dermatomyositis; 16 had scleroderma; eight had ankylosing spondylitis; five had juvenile RA; three had discoid lupus erythematosus; and four had 4 mixed connective tissue disorders (MCTD). The mean follow-up duration of curative cases was more than 6 years. Doses ranged from 10 to 87.6 Gy, with a median of 45 Gy. RESULTS: Overall, 263 sites were assessable in 209 patients. Significant (> or = grade 3) acute toxicity was seen in 10% of irradiated sites. Severe late effects were associated with significant acute reactions and with non-RA CVDs (6% v 21% at 5 years). No difference was seen in late effects according to timing of CVD onset, presence of concurrent vascular insults, radiation dose, or other technical factors, or by measures of disease activity. CONCLUSION: RA does not appear to have an elevated rate of late toxicity. While non-RA CVD is significantly associated with increased radiation late effects at standard doses, radiation-related mortality remains exceedingly rare. The choice of therapeutic modality in this radiosensitive group of patients should be made on a case-by-case basis.

mILIB: a new concept in laser therapy / mILIB: un nuevo concepto en laserterapia

mILIB (Intravascular Laser Irradiation in the Modified Bloodstream) presents itself as one more photobiomodulation technique, among the many therapeutic possibilities we know. The advantage in this case is the possibility of making application in a systemic way in which the organism as a whole is benefited. The use of the red therapeutic laser in a transcutaneous way, has been a great option as an added therapeutic value to the treatment of several pathologies, providing systemic stimuli, similar to hemotherapy. Thus, mILIB presents itself as an effective and increasingly widespread technique for professionals working with photobiomodulation

mILIB (Irradiación láser intravascular en el torrente sanguíneo modificado) se presenta como una técnica de fotobiomodulación más, entre las muchas posibilidades terapéuticas que conocemos. La ventaja en este caso es la posibilidad de realizar una aplicación de forma sistémica en la que se beneficia al organismo en su conjunto.El uso del láser terapéutico rojo de forma transcutánea, ha sido una gran opción como valor terapéutico añadido al tratamiento. de varias patologías, proporcionando estímulos sistémicos, similar a la hemoterapia. Así, mILIB se presenta como una técnica eficaz y cada vez más extendida para los profesionales que trabajan con fotobiomodulación.

The dose distribution produced by a 32P source for endovascular irradiation.

PURPOSE: Percutaneous transluminal coronary angioplasty (PTCA) is one of the most common therapies for obstructive coronary artery disease. Unfortunately, subsequent restenosis after percutaneous balloon angioplasty occurs in 30-50% of patients and remains one of the major unsolved problems of contemporary cardiology. The study of endovascular irradiation has been greatly stimulated by the discovery that the process of restenosis may be impaired by irradiation. The objective of this study was to examine a custom-made commercial 32P wire and to determine whether the present source presentation is suitable for this application. METHODS AND MATERIALS: Measurements of the dose distribution around a 3 mm long 32P source with an activity of 0.414 GBq (11.2 mCi) were made by using LiF thermoluminescent dosimeters and a scintillation detector. The source had the dimensions of 0.3 mm in diameter and 3 mm in length, and was first encapsulated by a plastic tube and then encapsulated in a specially manufactured Ni-Ti wire with a diameter of 0.4 mm and a length of 2.6 m. The detector size effect is removed from the measurements calculation. Loevinger's equation for the dose distribution around a 32P source was used for the calculations. RESULTS: The dose rate at a radial distance of 1.5 mm was 53 cGy/s per GBq (1.96 cGy/s per mCi) and fell off rapidly perpendicularly to the axis of the source in an approximately exponential manner, from 53-5.3 cGy/s per GBq (approximately 2 to 0.2 cGy/s per mCi) as radial distances increased from 0.2 to 0.4 g/cm2 (1.5 to 3.5 mm away from the center of the source). The treatment length parallel along the wire could be as long as 24 mm for eight source dwell positions with the average dose rate of 59 cGy/s per GBq (2.2 cGy/s per mCi) and a variation of +/- 2.3% at a radial distance of 1.5 mm. CONCLUSIONS: Our experiments show that the dose distribution is ideal for endovascular irradiation. The source was incorporated in the end of a flexible cable and with a half-life of 14.3 days is suitable for endovascular irradiation.

High beta and electron dose from 192Ir: implications for "gamma" intravascular brachytherapy.

PURPOSE: Trains of multiple 192Ir seeds are used in many clinical trials for intravascular brachytherapy. 192Ir source is commonly considered as a gamma emitter, despite the understanding that this radionuclide also emits a wide range of electron and beta energies, with a similar range of energy. The high dose from betas and electrons in the submillimeter range due to unsealed ends of seed sources should be precisely quantified to fully understand the backdrop for complications associated with 192Ir coronary artery brachytherapy. METHODS AND MATERIALS: Monte Carlo simulations (MCNP4C code) were performed for a model 5-seed 192Ir train used in SCRIPPS, GAMMA, and the Washington Radiation for In-Stent Restenosis (WRIST) randomized clinical trials. A stack of radiochromic films was also used to measure the dose distributions for an actual 6-seed train. RESULTS: In the submillimeter range very close to the source, Monte Carlo results show that betas and electrons deposit a higher dose than 192Ir photons (gamma and X-rays) over the interseed gap. A high luminal dose from the combined effects of betas, electrons, and photons emitted from 192Ir can be deposited, particularly between seeds. When prescribing 15 Gy at 2 mm, the combined dose can be as high as 160 Gy at 0.5 mm. Different peak doses near the interseed gaps were noted, which may be due to variability of seed-end surfaces and nonuniformity of seed activity within a real multiseed train. Dose-volume histograms (DVH) of lumen surfaces were evaluated for an eccentric seed train. The DVH parameters indicating the extent of hot spots in the lumen wall, DV(10), DV(5), DV(2), and DV(1) (dose received by 10, 5, 2, 1% respectively of the total lumen surface), can be as high as 55, 76, 81, and 155 Gy for a lumen with 3-mm diameter, and 75, 80, 110, and 158 Gy for a narrow 2-mm lumen. CONCLUSION: 192Ir multiple seed trains used in the SCRIPPS, GAMMA, and WRIST trials can deposit a very high dose to the luminal wall. A particularly high electron and beta dose can be delivered near the interseed gap if the source is not centered in the catheter and lumen. The dose from 192Ir betas and electrons may partially explain adverse outcomes reported from 192Ir multiseed clinical trials. Improvement of the encapsulation design to filter out the betas and electrons should be seriously considered.

Results of radiotherapy for chemodectomas.

Between 1974 and 1988, 10 Mayo Clinic patients had unresectable, locally recurrent, or partially resected chemodectomas. Of these 10 tumors, 9 were confirmed pathologically, and 1 was diagnosed clinically. The chemodectoma was located in the jugular bulb in five patients, the middle ear in three, and the carotid body in two. The following symptoms were noted: tinnitus (in eight patients), loss of hearing (in six), hoarseness (in six), dysphagia (in four), pain (in three), and alteration of mental status (in one). Many patients had more than one symptom. Treatment was delivered with megavoltage photons and electrons; total doses ranged from 16.2 to 52 Gy (median, 46 Gy), and the daily doses ranged from 1.6 to 2.4 Gy. Follow-up among the nine survivors ranged from 3 1/2 to 16 years (median, 7 1/2 years). In one patient, the response could not be assessed because the patient died of renal failure 4 months after treatment. All nine assessable patients had decreased symptoms and objective control of the tumor (no evidence of progression of disease). Of the nine assessable patients, four had complete responses, one had a partial response, and four had stable disease. No patient experienced progression of disease after radiotherapy. We conclude that radiotherapy for chemodectomas yields successful results--namely, decreased symptoms and objective control of the tumor.

Long-term palliation of pulmonary artery sarcoma by radical excision and adjuvant therapy.

The case of an extensive pulmonary artery sarcoma managed by radical excision and homograft reconstruction followed by aggressive chemotherapy and irradiation with prolonged survival is presented. Pulmonary artery sarcomas are reviewed with emphasis on the diagnosis and management of these usually fatal tumors.

System for the automated photothermal treatment of cutaneous vascular lesions.

It is well known that the use of tightly focused continuous wave lasers can be an effective treatment of common telangiactasia. In general, the technique requires the skills of a highly dexterous surgeon using the aid of optical magnification. Due to the nature of this approach, it has proven to be largely impractical. To overcome this, we have developed an automated system that alleviates the strain on the user associated with the manual tracing method. The device makes use of high contrast illumination, simple monochromatic imaging, and machine vision to determine the location of blood vessels in the area of interest. The vessel coordinates are then used as input to a two-dimensional laser scanner via a near real-time feedback loop to target, track, and treat. Such mechanization should result in increased overall treatment success, and decreased patient morbidity. Additionally, this approach enables the use of laser systems that are considerably smaller than those currently used, and consequently the potential for significant cost savings. Here we present an overview of a proof-of-principle system, and results using examples involving in vivo imaging of human skin.

Monte Carlo dose characterization of a new 90Sr/90Y source with balloon for intravascular brachytherapy.

Beta emitting source wires or seeds have been adopted in clinical practice of intravascular brachytherapy for coronary vessels. Due to the limitation of penetration depth, this type of source is normally not applicable to treat vessels with large diameter, e.g., peripheral vessel. In the effort to extend application of its beta source for peripheral vessels, Novoste has recently developed a new catheter-based system, the Corona 90Sr/90Y system. It is a source train of 6 cm length and is jacketed by a balloon. The existence of the balloon increases the penetration of the beta particles and maintains the source within a location away from the vessel wall. Using the EGSnrc Monte Carlo system, we have calculated the two-dimensional (2-D) dose rate distribution of the Corona system in water for a balloon diameter of 5 mm. The dose rates on the transverse axis obtained in this study are in good agreement with calibration results of the National Institute of Standards and Technology for the same system for balloon diameters of 5 and 8 mm. Features of the 2-D dose field were studied in detail. The dose parameters based on AAPM TG-60 protocol were derived. For a balloon diameter of 5 mm, the dose rate at the reference point (defined as r0 = 4.5 mm, 2 mm from the balloon surface) is found to be 0.01028 Gy min(-1) mCi(-1). A new formalism for a better characterization of this long source is presented. Calculations were also performed for other balloon diameters. The dosimetry for this source is compared with a 192Ir source, commonly used for peripheral arteries. In conclusion, we have performed a detailed dosimetric characterization for a new beta source for peripheral vessels. Our study shows that, from dosimetric point of view, the Corona system can be used for the treatment of an artery with a large diameter, e.g., peripheral vessel.

Monte Carlo modeling of radiation dose distributions in intravascular radiation therapy.

Radiation dose distributions are developed for balloon and wire sources of radioactivity within coronary arteries. The Monte Carlo codes MCNP 4B and EGS4 were used to calculate dose distributions for photons and electrons at discrete energies around such sources, with and without the presence of a high-density atherosclerotic plaque. An interactive computer program was developed which then calculates dose distributions for many radionuclides by applying the emission spectra to the discrete energy grids calculated by the Monte Carlo codes, weighting appropriately for electron energy and abundance. Results for Re-186 and Re-188 balloon sources are shown in comparison to an Ir-192 wire source. The program provides dose distributions as well as estimates of activity levels needed to deliver prescribed doses to the vessel wall at selected distances from the lumen in a selected time interval. In addition, dose calculations are presented in this paper for other organs in the body, from photon radiation as well as from possible loss of liquid activity into the bloodstream in the case of a balloon rupture. These results, especially the interactive computer program permitting easy comparison of various radionuclides and their physical characteristics, will greatly facilitate the comparison process and aid in the selection of the best candidate(s) for clinical use.

Dosimetric characteristics of a linear array of gamma or beta-emitting seeds in intravascular irradiation: Monte Carlo studies for the AAPM TG-43/60 formalism.

In principle, the AAPM TG-43/60 formalism for intravascular brachytherapy (IVBT) dosimetry of catheter-based sources is fully valid with a single seed of cylindrical symmetry and in the region comparable to or larger than the mean-free path of emitting radiation. However, for the geometry of a linear array of seeds within the few millimeter range of interest in IVBT, the suitability of the AAPM TG-43/60 formalism has not been fully addressed yet. We have meticulously investigated the dosimetric characteristics of catheter-based gamma (192Ir) and beta (90Sr/Y) sources using Monte Carlo methods before applying the AAPM TG-43/60 formalism. The dosimetric perturbation due to radiation interactions with neighboring seeds is at most 2% over the entire region of interest for the 192Ir source, while it increases to about 5% for the 90Sr/Y source. As the transaxial distance (y) increases beyond 3 mm, the sum of the dose contributions from neighboring seeds exceeds the dose contribution from the center seed for both sources. However, it continues to increase with the increasing y for 192Ir but is saturated beyond y = 5 mm for 9Sr/Y. Even within a few millimeters from the seeds, the dose from the low-energy betas of 192Ir is still less than 1% of the total dose. The radial dose and anisotropy functions are reformulated in reduced cylindrical coordinate with the reference point at y = 2 mm. The dose rate constant of 192Ir and the dose rate of 90Sr/Y at the reference point showed a fairly good agreement (within +/- 2%) with earlier studies and the NIST-traceable value, respectively. We conclude that the dosimetric perturbation caused by close proximity of neighboring seeds is nearly negligible so that the AAPM TG-43/60 formalism can be applied to a linear array of seeds.

IVBTMC, a Monte Carlo dose calculation tool for intravascular brachytherapy.

A new Monte Carlo code (IVBTMC) is developed for accurate dose calculations in intravascular brachytherapy (IVBT). IVBTMC calculates the dose distribution of a brachytherapy source with arbitrary size and curvature in a general three-dimensional heterogeneous medium. Both beta and gamma sources are considered. IVBTMC is based on a modified version of the EGSNRC code. A voxel-based geometry is used to describe the target medium incorporating heterogeneities with arbitrary composition and shape. The source term is modeled using appropriate phase-space data. The phase-space data are calculated for three widely used sources (32P, 90Sr/90Y, and 192Ir). To speed up dose calculations for gamma sources, a special version of IVBTMC based on the kerma approximation is developed. The accuracy of the phase-space data model is verified and IVBTMC is validated against other Monte Carlo codes and against reported measurements using radio-chromic films. To illustrate the IVBTMC capabilities, a variety of examples are treated. 32P, 90Sr/90Y, and 192Ir sources with different lengths and degrees of curvature are considered. Calcified plaques with regular and irregular shapes are modeled. The dose distributions are calculated with a spatial resolution ranging between 0.1 and 0.5 mm. They are presented in terms of isodose contour plots. The dosimetric effects of the source curvature and/or the presence of calcified plaques are discussed. In conclusion, IVBTMC has the capability to perform high-precision IVBT dose calculations taking into account the realistic configurations of both the source and the target medium.