Femoral Fracture in Primary Soft-Tissue Sarcoma of the Thigh and Groin Treated with Intensity-Modulated Radiation Therapy: Observed versus Expected Risk.

PURPOSE: This study was designed to compare the observed risk of femoral fracture in primary soft-tissue sarcoma (STS) of the thigh/groin treated with intensity-modulated radiation therapy (IMRT) to expected risk calculated using the Princess Margaret Hospital (PMH) nomogram. METHODS: Expected femoral fracture risk was calculated by using the PMH nomogram. Cumulative risk of fracture was estimated by using Kaplan-Meier statistics. Prognostic factors were assessed with univariate and multivariate analysis using Cox's stepwise regression. RESULTS: Between February 2002 and December 2010, 92 consecutive eligible patients were assessed. Median follow-up was 73 months (106 months in surviving patients). IMRT was delivered preoperatively (50 Gy) in 13 (14%) patients and postoperatively in 79 (86%) patients (median dose, 63 Gy; range, 59.4-66.6 Gy). The observed crude risk of fractures was 6.5% compared with 25.6% expected risk from the nomogram; the cumulative risk of fracture using IMRT at 5 years was 6.7% (95% CI 2.8-16.0%). The median time to fracture was 23 months (range, 6.9-88.6). Significant predictors of fracture on univariate analysis were age ≥ 60 years (p = 0.03), tumor location in the anterior thigh (p = 0.008), and periosteal stripping to > 20 cm (p < 0.0001). On multivariate analysis, age ≥ 60 years and periosteal stripping > 20 cm retained significance (p = 0.04 and p = 0.009, respectively). CONCLUSIONS: In this study, the cumulative risk of femur fracture in patients treated with IMRT (6.7%) is less than the expected risk using the PMH nomogram (25.6%). Established predictors of femur fracture, such as gender, tumor size, and dose of RT, seem to have less impact on fracture risk when using IMRT.

Interactive thermal tissue reactions of 7-MHz intense focused ultrasound and 1-MHz and 6-MHz radiofrequency on cadaveric skin.

BACKGROUND: Intense focused ultrasound (IFU) and radiofrequency (RF) systems generate thermal tissue reactions in multiple zones in the skin, with the microscopic features thereof varying according to energy sources and treatment parameters. OBJECTIVE: To evaluate interactive thermal tissue reactions of IFU and RF in cadaveric skin. METHODS: Thermal reaction patterns generated by IFU, invasive bipolar RF, and non-invasive monopolar RF treatments were analyzed in cadaveric skin of the inner thigh. Additionally, combination treatment, including IFU and invasive bipolar RF, IFU and non-invasive monopolar RF, invasive bipolar RF and IFU, and non-invasive monopolar RF and IFU, was delivered to cadaveric skin and microscopically evaluated. RESULTS: Combination treatment with 1.5-mm IFU followed by 1.5-mm invasive RF elicited multiple thermal injury zones of coagulation and ablation in the mid to lower dermis. Therein, IFU-induced thermal reactions were indistinguishable from RF-induced thermal reactions. Non-invasive RF treatment on IFU-pretreated cadaveric tissue specimens exhibited greater degrees of thermal injury, with wider and deeper penetration, compared to non-invasive RF treatment alone. Furthermore, RF-pretreated tissues showed marked differences in the patterns of IFU-induced thermal tissue reactions. CONCLUSION: Our data suggest that combination treatments with IFU and RF elicit various patterns of interactive thermal tissue reactions.

Radiation treatment for chemotherapy-resistant non-Hodgkin's lymphoma in the left thigh.

Extranodal non-Hodgkin lymphomas (NHLs) arising in soft tissue is rare. This study describes a rare case of chemo-resistant large B-cell NHL of skeletal muscle, characterized by voluminous swelling in the thigh which responded well to radiotherapy. In this patient, recurrent NHL showed refractoriness to various chemotherapy regimens and was treated with radiation therapy repeatedly with excellent local response and no evidence of disease for 18 months. Most of the published literature describes surgery or chemotherapy as treatment for NHL soft tissue. This is the first case report describing the durable response with radiation without in-field recurrence in chemo-resistant large B-cell NHL skeletal muscle.

Morphometric analysis of high-intensity focused ultrasound-induced lipolysis on cadaveric abdominal and thigh skin.

Non-focused ultrasound and high-intensity focused ultrasound (HIFU) devices induce lipolysis by generating acoustic cavitation and coagulation necrosis in targeted tissues. We aimed to investigate the morphometric characteristics of immediate tissue reactions induced by 2 MHz, 13-mm focused HIFU via two-dimensional ultrasound images and histologic evaluation of cadaveric skin from the abdomen and thigh. Acoustic fields of a 2 MHz, 38-mm HIFU transducer were characterized by reconstruction of the fields using acoustic intensity measurement. Additionally, abdominal and thigh tissues from a fresh cadaver were treated with a HIFU device for a single, two, and three pulses at the pulse energy of 130 J/cm2 and a penetration depth of 13 mm. Acoustic intensity measurement revealed characteristic focal zones of significant thermal injury at the depth of 38 mm. In both the abdomen and thigh tissue, round to oval ablative thermal injury zones (TIZs) were visualized in subcutaneous fat layers upon treatment with a single pulse of HIFU treatment. Two to three HIFU pulses generated larger and more remarkable ablative zones throughout subcutaneous fat layers. Finally, experimental treatment in a tumescent infiltration-like setting induced larger HIFU-induced TIZs of an oval or columnar shape, compared to non-tumescent settings. Although neither acoustic intensity measurement nor cadaveric tissue exactly reflects in vivo HIFU-induced reactions in human tissue, we believe that our data will help guide further in vivo studies in investigating the therapeutic efficacy and safety of HIFU-induced lipolysis.

An Anatomical Approach to Evaluating and Treating Cellulite.

Cellulite is the common rippling or dimpling of skin of the thighs and buttocks of women, formed from a confluence of skin laxity, tethering fibrous septa, and fat herniation. We describe an anatomical approach to evaluating the cellulite patient and selecting the best treatment from among available non-invasive, minimally invasive, and invasive therapies. It is crucial to consider the anatomy of the patient and the morphology of cellulite while choosing a treatment. Diffuse rippling represents increased adiposity and/or increased skin laxity which may stand to benefit from lipolytic and skin tightening modalities. Dimpling represents tethering by fibrous septa which may stand to improve from subcision by minimally invasive devices such as Cell na. Patients with both morphologies may be treated with a combination of treatments or Cellulaze. Careful evaluation of the patient can help identify the best therapeutic strategy. J Drugs Dermatol. 2017;16(1):58-61..

Multiple cutaneous metastases in a patient of carcinoma tonsil - Report of a rare case.

Carcinoma tonsil with visceral metastasis is a rare entity, and cutaneous metastasis is seen even more infrequently. We present a case of a 55-year-old male with carcinoma tonsil having received concurrent chemo radiotherapy, presenting with multiple cutaneous metastases to the scalp and thigh. To the best of our knowledge, till date only two similar cases of carcinoma tonsil with cutaneous metastasis have been reported in the English literature.

Efficacy of neoadjuvant hypofractionated radiotherapy in patients with locally advanced myxoid liposarcoma.

BACKGROUND: Myxoid liposarcoma (MLPS) has been reported to be more radiosensitive compared with other soft tissue sarcomas (STS). The use of preoperative hypofractionated radiotherapy 5 × 5 Gy for five consecutive days, and then immediate surgery in patients with locally advanced STS showed a good local control rate. The main objective of our work was to assess the efficacy of hypofractionated radiotherapy in preoperative setting in patients with locally advanced primary MLPS. METHODS: From February 1999 to March 2014, 32 patients with primary MLPS were treated with preoperative hypofractionated radiotherapy for 5 consecutive days followed by immediate surgery (median dose 5 × 5 Gy). Median size of the tumor 10.5 cm. In one patient the tumor was located on the upper extremity, the other (31 patients) had their tumors located on the lower extremity. RESULTS: In 90% patients histologically negative surgical margins (R0) were obtained. 34% patients had distant recurrence of the disease, local recurrence was found in 9.3% of the patients. 5-year local relapse-free survival rate was 90% and overall survival was 68%. In all analyzed surgical specimens the radiotherapy response features (hyalinization, fibrosis, paucicelularity, hemorrhages, dilatation of vessels) were detected. We have not found statistically significant differences in terms of OS and LRFS for RCC component, tumor grade, BCL2, TP53, postsurgery necrosis and tumor size. In postradiotherapy specimens significantly higher positivity of TP53 expression was detected as compared to primary biopsies. CONCLUSION: Combined therapy with hypofractionated radiotherapy followed by immediate surgery seems to be effective therapy in MLPS demonstrating good local control and pathological response to therapy.

Prospective Internally Controlled Blind Reviewed Clinical Evaluation of Cryolipolysis Combined With Multipolar Radiofrequency andVaripulseTechnology for Enhanced Subject Results in Circumferential Fat Reduction and Skin Laxity of the Flanks.

BACKGROUND: Increasing demand for non-invasive skin tightening and body contouring procedures has led to several technological in- novations in energy-based devices such as ultrasound, radiofrequency and cryolipolysis. An emerging trend in the eld is to evaluate whether combination therapies for skin laxity/body contouring using energy-based devices can deliver superior clinical results and patient satisfaction. As such, the objective of this prospective, internal-controlled, blind clinical study was to assess the safety and efficacy of cryolipolysis followed by multipolar radiofrequency with pulsed electromagnetic elds (PEMF) and adjustable pulsed suction for the treatment of skin laxity in the flanks. METHODS: Ten subjects with focal adiposities in the anks were enrolled in the study. All subjects received one session of cryolipolysis treatment and after randomization received two sessions of radiofrequency with PEMF (spaced two weeks apart), followed by another two sessions of radiofrequency with PEMF and adjustable pulsed suction (spaced two weeks apart). Clinical photography was used to monitor the subject's results at baseline, one week, three, and six months post treatment. Blinded reviewers and the treating inves- tigator assessed the clinical outcomes using the Global Aesthetic Improvement (GAI) scale. Side effects were recorded at every visit and patient satisfaction was noted at the one week, three and six-month follow-up using a 5-scale subject satisfaction assessment questionnaire. RESULTS: Analysis of the blinded investigator ratings demonstrated statistical significant enhanced skin laxity mean improvement of 1 grade on the GAI scale in subject treated with the combination treatment (cryolipolysis+RF/PEMF/suction) compared with the cryolipolysis treatment alone. The unblinded investigator GAI ratings also showed enhanced (20%) mean improvement of laxity in the combination treated subjects versus those receiving cryolipolysis alone. Over half of the participants reported satisfaction with both treatment results, but there was a 10% statistically significant higher satisfaction rating of the outcomes in the flank treated with the combination treatment. Procedures were well tolerated, side effects were transient and self-resolving and no unexpected adverse effects were reported for the duration of the study. CONCLUSION: The results of this study show that the combination of multipolar RF with PEMF/suction following cryolipolysis is a safe, effective, and painless approach to enhance skin tightening following fat reduction procedures in the flanks. J Drugs Dermatol. 2016;15(11):1354-1358..

Comparison of Efficacy Between Novel Robot-Assisted Laser Hair Removal and Physician-Directed Hair Removal.

OBJECTIVE: This study aimed to evaluate the number of laser irradiation sessions, process duration, and hair removal rate required for robot-assisted automatic versus physician-directed laser hair removal. BACKGROUND DATA: This research group previously developed and tested an automatic laser hair removal (LHR) system to provide uniform laser treatment distribution. METHODS: Six subjects 20-40 years of age, with skin types III-IV completed this study. A home-use LHR device with an 810 nm diode laser was used to treat equal-sized areas of both upper thighs; a random computer generator determined the use of a robot-assisted automatic LHR system or physician-directed LHR on the right or left thigh. The treatment schedule comprised five visits; subjects were photographed and shaved, and received LHR during the first through the fourth visits at 2-week intervals. The fifth visit occurred 1 month after the fourth, and only involved photography. RESULTS: All subjects successfully completed the clinical trial with no noticeable or permanent side effects. The average hair removal rates were 49.0% (standard error of the mean [SEM]: 4.0) and 29.5% (SEM: 4.0) for robot-assisted and physician-directed LHR, respectively. The average treatment duration and number of irradiation shots were 18 min, 30 sec (SEM: 33 sec) and 260 (SEM: 5.7) for robot-assisted LHR and 3 min, 11 sec (SEM: 15 sec) and 73 (SEM: 5.9) for physician-directed LHR. CONCLUSIONS: This clinical study successfully demonstrated the safety and effectiveness of robot-assisted LHR. The proposed novel system will benefit both patients and clinicians.

Does hypericin boost the efficacy of high-power laser? A preliminary experimental study on rats / A hipericina aumenta a eficácia do laser de alta potência? Um estudo preliminar e experimental em ratos

CONTEXT AND OBJECTIVE: Lasers are widely used in treating symptomatic benign prostatic hyperplasia. In current practice, potassium titanyl phosphate (KTP) lasers are the most common type of laser systems used. The aim here was to evaluate the rapid effect of high-power laser systems after application of hypericin. DESIGN AND SETTING: Experimental animal study conducted in the Department of Urology, Gülhane Military Medical Academy, Ankara, Turkey, in 2012. METHODS: Sixteen rats were randomized into four groups: 120 W KTP laser + hypericin; 120 W KTP laser alone; 80 W KTP laser + hypericin; and 80 W KTP laser alone. Hypericin was given intraperitoneally two hours prior to laser applications. The laser incisions were made through the quadriceps muscle of the rats. The depth and the width of the laser incisions were evaluated histologically and recorded. RESULTS: To standardize the effects of the laser, we used the ratio of depth to width. These new values showed us the depth of the laser application per unit width. The new values acquired were evaluated statistically. Mean depth/width values were 231.6, 173.6, 214.1 and 178.9 in groups 1, 2, 3 and 4, respectively. The most notable result was that higher degrees of tissue penetration were achieved in the groups with hypericin (P < 0.05). CONCLUSIONS: The encouraging results from our preliminary study demonstrated that hypericin may improve the effects of KTP laser applications. .

CONTEXTO E OBJETIVO: Lasers são amplamente utilizados no tratamento de hiperplasia benigna de próstata sintomática. Na prática atual, lasers de fosfato de titanilo de potássio (KTP) são os tipos mais comuns usados dos sistemas. O objetivo foi avaliar o efeito rápido do sistema laser de alta potência após a aplicação de hipericina. TIPO DE ESTUDO E LOCAL: Estudo experimental animal, realizado no Departamento de Urologia, Academia de Medicina Militar de Gülhane, Ancara, Turquia, em 2012. MÉTODOS: 16 ratos foram divididos aleatoriamente em 4 grupos: 120W KTP laser + hipericina; 120W KTP laser somente; 80W KTP laser + hipericina; 80W KTP laser somente. Hipericina foi dada intraperitonealmente duas horas antes da aplicação do laser. As incisões a laser foram feitas através do músculo quadríceps dos ratos. A profundidade e a largura das incisões a laser foram avaliadas histologicamente e registradas. RESULTADOS: Para padronizar o efeito do laser foi utilizada a razão entre profundidade e largura. Estes novos valores nos mostraram a profundidade da aplicação do laser de largura por unidade. Os novos valores adquiridos foram avaliados estatisticamente. Os valores da média de profundidade/largura foram 231,6, 173,6, 214,1 e 178,9 nos grupos 1, 2, 3 e 4, respectivamente. O resultado mais notável foi atingir altos graus de penetração tecidual nos grupos com hipericina (P < 0,05). CONCLUSÕES: Os resultados promissores do nosso estudo preliminar mostraram que hipericina pode melhorar os efeitos das aplicações do laser KTP. .

Does hypericin boost the efficacy of high-power laser? A preliminary experimental study on rats.

CONTEXT AND OBJECTIVE: Lasers are widely used in treating symptomatic benign prostatic hyperplasia. In current practice, potassium titanyl phosphate (KTP) lasers are the most common type of laser systems used. The aim here was to evaluate the rapid effect of high-power laser systems after application of hypericin. DESIGN AND SETTING: Experimental animal study conducted in the Department of Urology, Gülhane Military Medical Academy, Ankara, Turkey, in 2012. METHODS: Sixteen rats were randomized into four groups: 120 W KTP laser + hypericin; 120 W KTP laser alone; 80 W KTP laser + hypericin; and 80 W KTP laser alone. Hypericin was given intraperitoneally two hours prior to laser applications. The laser incisions were made through the quadriceps muscle of the rats. The depth and the width of the laser incisions were evaluated histologically and recorded. RESULTS: To standardize the effects of the laser, we used the ratio of depth to width. These new values showed us the depth of the laser application per unit width. The new values acquired were evaluated statistically. Mean depth/width values were 231.6, 173.6, 214.1 and 178.9 in groups 1, 2, 3 and 4, respectively. The most notable result was that higher degrees of tissue penetration were achieved in the groups with hypericin (P < 0.05). CONCLUSIONS: The encouraging results from our preliminary study demonstrated that hypericin may improve the effects of KTP laser applications.

Noninvasive treatment of cellulite utilizing an expedited treatment protocol with a dual wavelength laser-suction and massage device.

BACKGROUND: Over the past few years, noninvasive devices based on radiofrequency and/or lasers and light sources technologies are being used for the treatment of cellulite. OBJECTIVES: To evaluate the effects of an expedited treatment for cellulite and body measures. METHODS: Fifteen female subjects aged from 20 to 42 years were enrolled. All the subjects underwent three treatment sessions of 30 minutes for each area in three consecutive days. Subjects were evaluated at 7, 30, and 60 post treatment. Outcome measurements included Cellulite Severity Scale (CSS) grading, body mass index (BMI), and thigh circumferences were recorded. Celluqol(®) and a satisfaction questionnaire were also applied. RESULTS: At 2 months, improvements in at least one of the four CSS categories were found in 14 of the 15 subjects (93%) while 60% of patients showed improvement in both the number and depth of depressions at follow-up visits. Most of patients (93%) reported that they would get the treatment again. DISCUSSION: This was the first study to examine the effects of this device on cellulite performed over a shortened treatment period. The treatment proved to be safe and effective, representing a new treatment modality that is also time and cost-effective for physicians and patients.

A multicenter study for a single, three-step laser treatment for cellulite using a 1440-nm Nd:YAG laser, a novel side-firing fiber, and a temperature-sensing cannula.

BACKGROUND: Historically, treatments for cellulite have not been able to address all of its physiological components and require multiple sessions. OBJECTIVE: The authors evaluate the safety and efficacy of a single, subdermal procedure to treat the underlying structure of cellulite. METHODS: Fifty-seven patients underwent a 3-step cellulite treatment with a 1440-nm Nd:YAG laser with a side-firing fiber and temperature-sensing cannula. Efficacy was measured by the ability of blinded evaluators to distinguish baseline photos from those taken at 3 and 6 months posttreatment, as well as their rating of the results on a 5-point, 2-category ordinal photonumeric scale when comparing baseline photos to those taken at 2, 3, and 6 months posttreatment. Patient and physician satisfaction was assessed based on completion of a satisfaction survey at 2, 3, and 6 months posttreatment. Adverse events (AE) were recorded throughout the study. RESULTS: At 6 months posttreatment, blinded evaluators rated at least a 1-point improvement in the appearance of cellulite in 96% of treated sites. Blinded evaluators were also able to correctly identify baseline versus posttreatment photos in 95% of cases. At least 90% of patients and physicians reported satisfaction with the results of treatment throughout 6 months. AE were mild in intensity and transient to treatment. CONCLUSIONS: A single, 3-step, minimally invasive laser treatment using a 1440-nm Nd:YAG laser, side-firing fiber, and temperature-sensing cannula to treat the underlying structure of cellulite proved to be safe and maintained effectiveness at least 6 months posttreatment. LEVEL OF EVIDENCE: 2.

Computation electrical variables induced by magnetic stimulation in 3D thigh model.

This paper presents the changes in the electrical variables induced in a 3D thigh model with femoral diaphyseal fracture when it is magnetically stimulated. Three cases with particular geometries of the models were considered: skin, muscle, cortical bone (CB), bone marrow, metal pin, and fracture shape. Fracture shape included electric properties for blood, cartilage, trabecular bone (TB), and cortical bone (CB), to represent the consolidation process. A Helmholtz coil was added to the thigh model as stimulation source. The stimulation signal was between 0.5 and 2 mT, and between 5 and 100 Hz. The results shown than induced electric signals were higher for a change in frequency than a change in magnetic field. An important dependence between frequency, magnetic field, fracture shape, and fracture properties was found. The result suggest that the consolidation process could be better if different magnetic stimulation levels were considered.

Pathologic femur fractures after limb-sparing treatment of soft-tissue sarcomas.

INTRODUCTION: Local control for sarcomas of the long bones includes limb sparing surgery and radiotherapy. While effective, there are potential complications. METHODS: Patients treated for a soft tissue sarcoma of the thigh with limb-sparing surgery and radiation therapy between 1986 and 2000 at the University of Minnesota Masonic Cancer Center (n=89) were identified. Demographic, tumor, and treatment characteristics were abstracted from the medical record. Univariate analysis was conducted to identify significant risk factors for fracture. RESULTS: Survivors (58% male), median age of 50 (7-88) years, reported 8 (9%) fractures at a median of 7.3 (0.8-21.9) years from diagnosis after a median of 6300 (2000-7020) cGy of radiation. All fractures occurred within the previous radiation field, after no trauma. Three of the 8 (37.5%) had delayed union, 2 (25%) nonunion healing. Significant risk factors included periosteal stripping (p=0.006), anterior compartment location (p=0.022), and having 100% of the femoral circumference irradiated (p=0.018). Taking into account time to fracture using Kaplan Meier and log rank tests, these same predictors were identified. Older age, female sex, use of chemotherapy, and timing of radiation were not predictive of femoral fracture. CONCLUSION: Anterior tumor location, periosteal stripping, and radiation to 100% of the femur circumference are associated with femoral fracture. These patients require long-term monitoring and may warrant prophylactic intramedullary pinning or other protective measures. IMPLICATIONS FOR CANCER SURVIVORS: Survivors of soft tissue sarcomas of the femur may be at risk for the development of femur fractures and warrant close observation.

Non-invasive therapy of wrinkles and lax skin using a novel multisource phase-controlled radio frequency system.

Abstract The last few years have shown an increased demand for non-invasive skin tightening to improve body contour. Since light (lasers or intense pulsed light sources) has a limited ability to penetrate deep into the tissue, radio frequency (RF) modalities were introduced for the reduction of lax skin to achieve skin tightening and body circumference reduction. This study presents the use of the novel 3DEEP technology for body contouring. 3DEEP is a next generation RF technology that provides targeted heating to deeper skin layers without pain or other local or systemic side effects associated with the use of the earlier generation RF systems available today. The study included 30 treatment areas on 23 healthy volunteers at two sites. The treatment protocol included four weekly and two bi-weekly (n= 6) treatments on different body areas. Results were evaluated by standardized photography and by circumference measurements at the treatment area, and were compared to changes in body weight. Significant improvement could be observed in wrinkles and skin laxity, and in the appearance of stretch marks and cellulite. Some changes appeared as early as after a single treatment. Circumference changes of up to 4.3 cm were measured.

Treatment of striae distensae with a TriPollar radiofrequency device: a pilot study.

BACKGROUND: Striae distensae are a frequent skin condition for which treatment remains a challenge. OBJECTIVES: To determine the efficacy and safety of a TriPollar radiofrequency (RF) device for the treatment of striae in skin phototypes IV-V. METHODS: Seventeen females with striae received six weekly treatments with a TriPollar RF device. The participants were evaluated using standardized photographs and a UVA-light video camera at baseline, and at 1 and 6 weeks after the final treatment. Side effects of treatment were recorded at every session. RESULTS: At 1 week after the final treatment, 38.2% and 11.8% of the subjects were assessed to have 25-50% and 51-75% improvement of their striae, respectively. Compared with the 1-week follow-up, at the 6-week follow-up a higher percentage of the subjects were rated to have improvement of their striae. There were no significant differences in the striae surface smoothness at the 1- (p = 0.907) and 6-week (p = 0.057) follow-ups, compared with that of baseline. Twelve percent (2/17), 23% (4/17), and 65% (11/17) of the study subjects rated their satisfaction of the overall improvement as slightly satisfied, satisfied, and very satisfied, respectively. No adverse effect was reported. CONCLUSION: TriPollar RF appears to be a promising alternative for the treatment of striae distensae.

A tracer dose of technetium-99m-labeled liposomes can estimate the effect of hyperthermia on intratumoral doxil extravasation.

PURPOSE: A noninvasive method to monitor intratumoral Doxil delivery in individual patients during targeted tumor therapy is important to predict treatment response. The purpose of this study was to determine if a small tracer dose of technetium-99m (99mTc)-labeled liposomes could be used to quantify the effect of local hyperthermia on intratumoral Doxil extravasation. EXPERIMENTAL DESIGN: Experiments were carried out in a rat fibrosarcoma model with transplanted thigh tumors. Liposomes of approximately same size and composition as Doxil were radiolabeled using [technetium-99m (99mTc)]exametazime. Eight treatment groups received either Doxil, a tracer dose or a large dose of 99mTc-labeled liposomes, or a combination of tracer and Doxil, with or without hyperthermia. This design was chosen to assure that coadministration of both liposomal formulations did not influence their intratumoral distribution. Hyperthermia was done for 45 minutes. Scintigraphic images were obtained at 5 and 18 hours. At 18 hours, tumors were removed and gamma counts as well as doxorubicin concentrations were measured. RESULTS: Intratumoral extravasation of the 99mTc-labeled tracer could be imaged scintigraphically under normothermic and hyperthermic conditions. The thermal enhancement ratio was slightly higher for radiolabeled liposomes than for doxorubicin concentration. However, there was a significant positive correlation of intratumoral doxorubicin concentration and intratumoral uptake of the radiolabeled tracer (expressed as percentage of the injected dose per gram of tissue). Coadministration of radiolabeled liposomes did not negatively influence the amount of drug delivered with Doxil. CONCLUSIONS: The use of a radiolabeled tracer has potential value to monitor drug delivery and estimate the effect of an intervention aimed to increase liposomal accumulation, such as local hyperthermia.

Effect of controlled volumetric tissue heating with radiofrequency on cellulite and the subcutaneous tissue of the buttocks and thighs.

BACKGROUND: Regardless of diet and exercise, genetics plays an important part in creating puckering skin or dimples, which are difficult to hide at any age. The demand for a nonsurgical, noninvasive treatment of cellulite has inspired some manufacturers to invest in a new age of sophisticated devices and treatment therapies to repair the skin and improve contours. Although many of these new choices have demonstrated a smoothing effect (following a multitude of treatments), the objective documentation has in most cases been limited to biopsies, circumference measurements, and photographic evidence. HYPOTHESIS: We believe that the application of noninvasive high-energy radiofrequency (RF) to the skin of the thigh and buttocks heats the subcutaneous adipose tissue, causing collagen fibers to contract. The resulting impact to the subcutaneous tissue and collagen is expected to improve the skin's external architecture. Given that the subcutaneous tissue and adipose tissue are difficult to evaluate through histological methods, this investigation seeks to demonstrate the changes that occur when applying 2 treatments of high-energy RF on the subcutaneous tissue of thighs and buttocks utilizing real-time ultrasound image scanning. MATERIALS AND METHODS: Twenty-six healthy female patients (ages 18 to 50) with visible bilateral cellulite (grade 1 to 3) on either the buttocks and/or thighs received 2 treatment sessions (15 days apart) of unipolar RF using the Accent RF System (Alma Lasers Inc). The system utilizes a unipolar RF applicator that is electrically cooled to aid in patient comfort during the treatment. Appropriate energy was set and the treatment was delivered in 3 passes of 30 seconds each. Evaluation of the thickness of the subcutaneous tissue on buttocks and thighs took place before the first treatment, second treatment, and 15 days following the second treatment with a with real-time scanning image ultrasound (Philips Medical Systems). Clinical improvement was objectively evaluated through comparative pre- and post-treatment measurements of the distance between the stratum corneum to the Camper's fascia and from the stratum corneum to the muscle. The study also evaluated the structure and changes of the collagen (thickening and realignment of septae) resulting from 2 treatments of RE Photography was used to document contour and superficial changes. RESULTS: From the measurements of the distance between the stratum corneum to the Camper's fascia and from the stratum corneum to the muscle we were able to demonstrate that 68% of the patients presented a contraction of the volume of approximately 20%. CONCLUSIONS: Based on the demonstrated results with real-time ultrasound scanning, we have observed that 2 RF treatments on the subcutaneous tissue of the buttocks and thighs provide a volumetric contraction effect in the majority of patients. This validates the primary hypothesis of our protocol and establishes that the RF energy works on the connective tissue of the subcutaneous adipose tissue. This effect should be the same on any other body part.