RESUMEN
Undifferentiated pleomorphic sarcoma not otherwise specified belongs to the heterogeneous group of soft tissue tumors. It is preferentially located in the upper and lower extremities of the body, and surgical resection remains the only curative treatment. Preclinical animal models are crucial to improve the development of novel chemotherapeutic agents for the treatment of undifferentiated pleomorphic sarcoma. However, this approach has been hampered by the lack of reproducible animal models. The present study established two xenograft animal models generated from stable non-clonal cell cultures, and investigated the difference in chemotherapeutic effects on tumor growth between undifferentiated pleomorphic sarcoma in vivo and in vitro. The cell cultures were generated from freshly isolated tumor tissues of two patients with undifferentiated pleomorphic sarcoma. For the in vivo analysis, these cells were injected subcutaneously into immunodeficient mice. The mice were monitored for tumor appearance and treated with the most common or innovative chemotherapeutic agents available to date. Furthermore, the same drugs were administered to in vitro cell cultures. The most effective tumor growth inhibition in vitro was observed with doxorubicin and the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA), also known as vorinostat. In the in vivo xenograft mouse model, the combination of doxorubicin and the tyrosine kinase inhibitor pazopanib induced a significant tumor reduction. By contrast, treatment with vorinostat did not reduce the tumor growth. Taken together, the results obtained from drug testing in vitro differed significantly from the in vivo results. Therefore, the novel and reproducible xenograft animal model established in the present study demonstrated that in vivo models are required to test potential chemotherapeutic agents for the treatment of undifferentiated pleomorphic sarcoma prior to clinical use, since animal models are more similar to humans, compared with in vitro cell cultures.
RESUMEN
UNLABELLED: The treatment of osteosarcoma, especially wide resection, is challenging. An additional local drug therapy after resection using anti-neoplastic bone cement (Polymethylmethacrylate (PMMA)) could help improve the outcome of therapy. In this study, we evaluated the effects of PMMA loaded with valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA) on the cell activity of a SaOs-2 cell culture, as well as the elution rate of the drugs out of the bone cement. MATERIALS AND METHODS: In our experiments, we used the SaOs-2 osteosarcoma and the SW1353 chondrosarcoma cell line. Bone cement clots (5 g) were prepared and loaded with different drug concentrations of VPA (25 mg and 50 mg) and SAHA (1 mg, 2.5 mg and 5 mg). Two control groups were established, one with a native cement clot, the other with human mesenchymal stem cells, in order to evaluate toxicity on non tumor-cells. Cell activity was measured using an Alamar Blue assay on days 1, 2, 3, 4 and 7. The cement clots were additionally examined in a material testing unit for biomechanical and structural changes. RESULTS: Tumor cells showed a significant and complete reduction of activity under therapy with VPA and SAHA. Drug release of VPA was extensive between days 0 and 3 and decreased progressively to day 7. Cumulative drug concentration in the medium continuously increased. Biomechanical testing of the cement clots showed no differences in stability and architecture compared to the control group. SaOs-2 and SW1353 cells with medium from native cement clots without drug therapy presented a cell activity of 100% in all groups and during all measurements. Human mesenchymal stem cells were not significantly affected during therapy with VPA and low concentrations of SAHA. In contrast, cell activity of human mesenchymal stem cells was significantly reduced under therapy with higher concentrations of SAHA, with an approximately linear decrease between days 0-3 and a rapidly decreasing activity between days 4-7. CONCLUSION: A local cytotoxic therapy in the treatment of osteosarcoma and chondrosarcoma might improve the rate of metastasis and survival of patients. Our results present an encouraging approach to loading PMMA with anti-neoplastic drugs.
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Cementos para Huesos/farmacología , Neoplasias Óseas/tratamiento farmacológico , Condrosarcoma/tratamiento farmacológico , Inhibidores de Histona Desacetilasas/farmacología , Osteosarcoma/tratamiento farmacológico , Polimetil Metacrilato/química , Apoptosis/efectos de los fármacos , Fenómenos Biomecánicos , Neoplasias Óseas/patología , Neoplasias Óseas/cirugía , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Condrosarcoma/patología , Condrosarcoma/cirugía , Humanos , Ácidos Hidroxámicos/farmacología , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/efectos de los fármacos , Osteosarcoma/patología , Osteosarcoma/cirugía , VorinostatRESUMEN
BACKGROUND AND PURPOSE: The diagnosis and treatment of isolated greater tuberosity fractures of the proximal humerus is not clear-cut. We retrospectively assessed the clinical and radiographic outcome of isolated greater tuberosity fractures. PATIENTS AND METHODS: 30 patients (mean age 58 (26-85) years, 19 women) with 30 closed isolated greater tuberosity fractures were reassessed after an average follow-up time of 3 years with DASH score and Constant score. Radiographic outcome was assessed on standard plain radiographs. RESULTS: 14 of 17 patients with undisplaced or slightly displaced fractures (≤ 5 mm) were treated nonoperatively and had good clinical outcome (mean DASH score of 13, mean Constant score of 71). 8 patients with moderately displaced fractures (6-10 mm) were either treated nonoperatively (n = 4) or operatively (n = 4), with good functional results (mean DASH score of 10, mean Constant score of 72). 5 patients with major displaced fractures (> 10 mm) were all operated with good clinical results (mean DASH score of 14, mean Constant score of 69). The most common discomfort at the follow-up was an impingement syndrome of the shoulder, which occurred in both nonoperatively treated patients (n = 3) and operatively treated patients (n = 4). Only 1 nonoperatively treated patient developed a non-union. By radiography, all other fractures healed. INTERPRETATION: We found that minor to moderately displaced greater tuberosity fractures may be treated successfully without surgery.
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Fracturas del Hombro/terapia , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Fijación Interna de Fracturas , Curación de Fractura , Humanos , Inmovilización , Masculino , Persona de Mediana Edad , Radiografía , Estudios Retrospectivos , Fracturas del Hombro/diagnóstico por imagen , Fracturas del Hombro/cirugía , Resultado del TratamientoRESUMEN
PURPOSE: To examine the feasibility and safety of magnetic resonance (MR)-guided biopsy by using a transgluteal approach in patients with suspicious prostate lesions by using an MR-compatible robotic system and a 1.5-T MR system. MATERIALS AND METHODS: The study was approved by the institutional review board of University Frankfurt, and informed consent was obtained from each patient. A total of 20 patients (age range, 57.8-71.9 years; mean age, 65.1 years) underwent biopsy in a closed-bore high-field-strength MR system. Biopsy was performed with an MR-compatible pneumatically driven robotic system. T1-weighted gradient-echo fast low-angle shot and T2-weighted true fast imaging with steady-state precession sequences were used to plan and guide the intervention with a transgluteal access on the external planning computer of the assistance system. The system calculated the trajectory and then moved the guiding arm to the insertion point. The cannula was advanced manually, and biopsies were performed with the coaxial technique by using a 15-gauge pencil tip needle. Intervention time, complications, and biopsy findings were documented. RESULTS: The MR-compatible robotic system did not interfere with image quality, nor did MR imaging cause dysfunction of the robot. In one patient, the interventionist caused a fail-safe system shutdown. This was due to inadvertent displacement of the guiding arm during cannula insertion. This problem was solved by increasing the displacement threshold. Accurate coaxial cannula biopsy could be performed in all subsequent patients. Sufficient histopathologic assessment was performed in 19 patients. Insufficient material was retrieved in the patient who experienced fail-safe system shutdown. The median intervention time was 39 minutes (23-65 minutes). No procedure-related complications were observed. CONCLUSION: Preliminary results indicate that MR-guided robot-assisted biopsy is feasible and can be performed safely with highly accurate cannula placement.
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Biopsia con Aguja/instrumentación , Imagen por Resonancia Magnética Intervencional/instrumentación , Neoplasias de la Próstata/diagnóstico , Robótica/instrumentación , Anciano , Artefactos , Estudios de Factibilidad , Humanos , Masculino , Persona de Mediana Edad , Posición Prona , Neoplasias de la Próstata/patología , Seguridad , Programas InformáticosRESUMEN
BACKGROUND AND AIMS: Facet joint denervation is a frequently performed technique to treat facet joint syndrome. Most often this technique is used under fluoroscopic guidance implicating high radiation doses for both patients and surgeons. This prospective study was performed to evaluate the effectiveness in reducing radiation dose during radiofrequency ablation therapy of the lumbar facet joints and to evaluate the feasibility and possibilities of the new real time image guidance system SabreSource. MATERIALS AND METHODS: As much as 20 consecutive patients with radiofrequency ablation therapy of the facet joints L4 to S1 were included. Ten patients were treated by fluoroscopic control alone; the following 10 patients were treated with the SabreSource image guidance system. A total of 40 thermal ablations to the facet joints were performed. Each patient was given one thermal ablation on both sides of the vertebral segment, either to the facet joints of L4-L5 or of L5-S1. Pain, according to the visual analogue scale (VAS), was documented before and 6 h after the intervention. Radiation dose, time of radiation and the number of shots needed to place the radiofrequency cannula were recorded. RESULTS: No complications occurred. Before therapy, the mean VAS in all patients was 7.6 (range 6-10). After therapy the mean VAS in all patients was 3.4 (range 0-5). Compared to the fluoroscopy-guided thermal ablation therapy the SabreSource system significantly reduced the number of fluoroscopy exposures (reduction 23.53%, p = 0.02), the time of radiation exposure (reduction 21.2%, p = 0.03) and the mean entrance surface dose (reduction 30.46%, p = 0.01). CONCLUSION: The SabreSource System reduces radiation exposure and radiation dose in the radiofrequency denervation therapy of the lumbar facet joints and can be applied for other minimally invasive techniques.
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Ablación por Catéter/instrumentación , Procesamiento de Imagen Asistido por Computador , Dosis de Radiación , Articulación Cigapofisaria/cirugía , Anciano , Ablación por Catéter/métodos , Enfermedad Crónica , Desnervación/métodos , Femenino , Fluoroscopía , Estudios de Seguimiento , Humanos , Dolor de la Región Lumbar/cirugía , Región Lumbosacra/cirugía , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Dimensión del Dolor , Estudios Prospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: The purpose of this study was to determine the efficacy and safety of radiofrequency ablation (RFA) of bone metastases of breast cancer and to compare RFA alone and RFA with additional bone cement application. The primary objectives were to compare pain reduction and quality of life during long-term follow-up in a prospective pilot study. PATIENTS AND METHODS: Sixteen female patients with painful spinal bone metastases of human breast cancer were included in this prospective pilot study (mean age 59.5 years, range 52 - 69 years). RFA was performed with computed tomographic guidance and under local anesthesia. A bipolar and impedance-controlled radiofrequency system was used. Following RFA, bone cement was injected into the necrosis cavity in half of the patients (n=8). Pain, quality of life and complications were evaluated. Mean follow-up time was 20.4 months (range 8-36). Paired comparison procedures were used for analysis of the results. A review of the literature was carried out. RESULTS: In both groups (RFA alone and RFA with additional bone cement application), pain was reduced significantly (mean reduction of pain 51.7%, p=0.0065). Quality of life was improved up to 61%. All procedures were performed without side-effects and complications. Imaging showed a complete ablation of the bone tumor in all patients. No local tumor progression was seen. CONCLUSION: RFA is a safe and effective option in the palliative therapy of bone tumors. Application of bone cement into the necrosis cavity has no significant additional effect on the reduction of pain and the improvement in quality of life. In selected cases with big bone defects, combining RFA and bone cement application is a useful option to stabilize the bone.
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Cementos para Huesos , Neoplasias Óseas/radioterapia , Neoplasias de la Mama/patología , Anciano , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/secundario , Femenino , Humanos , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , Tomografía Computarizada por Rayos XRESUMEN
Interventional procedures are associated with high radiation doses for both patients and surgeons. To reduce the risk from ionizing radiation, it is essential to minimize radiation dose. This prospective study was performed to evaluate the effectiveness in reducing radiation dose during facet joint injection in the lumbar spine and to evaluate the feasibility and possibilities of the new real time image guidance system SabreSource. A total of 60 patients, treated with a standardized injection therapy of the facet joints L4-L5 or L5-S1, were included in this study. A total of 30 patients were treated by fluoroscopy guidance alone, the following 30 patients were treated using the new SabreSource system. Thus a total of 120 injections to the facet joints were performed. Pain, according to the visual analogue scale (VAS), was documented before and 6 h after the intervention. Radiation dose, time of radiation and the number of exposures needed to place the needle were recorded. No significant differences concerning age (mean age 60.5 years, range 51-69), body mass index (mean BMI 26.2, range 22.2-29.9) and preoperative pain (VAS 7.9, range 6-10) were found between the two groups. There was no difference in pain reduction between the two groups (60 vs. 61.5%; P = 0.001) but the radiation dose was significantly smaller with the new SabreSource system (reduction of radiation dose 32.7%, P = 0.01; reduction of mean entrance surface dose 32.3%, P = 0.01). The SabreSource System significantly reduced the radiation dose received during the injection therapy of the lumbar facet joints. With minimal effort for the setup at the beginning of a session, the system is easy to handle and can be helpful for other injection therapies (e.g. nerve root block therapies).
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Fluoroscopía/métodos , Monitoreo Intraoperatorio/métodos , Dosis de Radiación , Traumatismos por Radiación/prevención & control , Cirugía Asistida por Computador/métodos , Articulación Cigapofisaria/cirugía , Anciano , Anestésicos Locales/administración & dosificación , Dolor de Espalda/tratamiento farmacológico , Dolor de Espalda/patología , Dolor de Espalda/fisiopatología , Femenino , Fluoroscopía/efectos adversos , Fluoroscopía/instrumentación , Humanos , Procesamiento de Imagen Asistido por Computador/instrumentación , Procesamiento de Imagen Asistido por Computador/métodos , Inyecciones Intraarticulares/métodos , Masculino , Persona de Mediana Edad , Monitoreo Intraoperatorio/instrumentación , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Estudios Prospectivos , Cirugía Asistida por Computador/instrumentación , Resultado del Tratamiento , Articulación Cigapofisaria/efectos de los fármacos , Articulación Cigapofisaria/fisiopatologíaRESUMEN
The aim of the study was to evaluate the feasibility, safety and effectiveness of CT-guided and MR-thermometry-controlled laser-induced interstitial thermotherapy (LITT) in adrenal metastases. Nine patients (seven male, two female; average age 65.0 years; range 58.7-75.0 years) with nine unilateral adrenal metastases (mean diameter 4.3 cm) from primaries comprising colorectal carcinoma (n = 5), renal cell carcinoma (n = 1), oesophageal carcinoma (n = 1), carcinoid (n = 1), and hepatocellular carcinoma (n = 1) underwent CT-guided, MR-thermometry-controlled LITT using a 0.5 T MR unit. LITT was performed with an internally irrigated power laser application system with an Nd:YAG laser. A thermosensitive, fast low-angle shot 2D sequence was used for real-time monitoring. Follow-up studies were performed at 24 h and 3 months and, thereafter, at 6-month intervals (median 14 months). All patients tolerated the procedure well under local anaesthesia. No complications occurred. Average number of laser applicators per tumour: 1.9 (range 1-4); mean applied laser energy 33 kJ (range 15.3-94.6 kJ), mean diameter of the laser-induced coagulation necrosis 4.5 cm (range 2.5-7.5 cm). Complete ablation was achieved in seven lesions, verified by MR imaging; progression was detected in two lesions in the follow-up. The preliminary results suggest that CT-guided, MR-thermometry-controlled LITT is a safe, minimally invasive and promising procedure for treating adrenal metastases.