RESUMEN
Interventional MRI is clearly in its early stages of development. While the value of MR-guided aspiration cytology and MR evaluation of deep electrode implantation in the brain has already been confirmed with human clinical studies, the future of MR-guided interstitial laser therapy remains to be proven. Despite this, as we look ahead into the 1990s and the millennium, it is possible to imagine dedicated MR laser therapy units for combined radiological and surgical outpatient approaches in what may become the operating rooms of the 21st century.
Asunto(s)
Neoplasias de Cabeza y Cuello/diagnóstico , Imagen por Resonancia Magnética/métodos , Biopsia con Aguja/métodos , Neoplasias de Cabeza y Cuello/terapia , Humanos , Terapia por Láser , Imagen por Resonancia Magnética/instrumentaciónRESUMEN
Kodak Q-switch II dye has recently proven to be an effective biostimulative agent on normal human fibroblast cultures. The potential for this dye as a new chemosensitizing agent for the treatment of connective tissue diseases and wound healing with the Nd:YAG laser was examined. Two normal fibroblast cell lines were first sensitized to a nontoxic dose of Q-switch II dye, then subjected to treatment with an Nd:YAG laser at 1,060 nm, with varying levels of energy and temperatures determined by a reproducible method of dosimetry. The results indicate that Q-switch II dye at nontoxic doses of 0.1 micrograms/ml enhances the cytotoxic effects of the Nd:YAG laser at temperatures as low as 36 degrees C. Furthermore, at physiological temperature ranges as low as 24 degrees C to 34 degrees C, cell duplication was inhibited, but cell viability was not affected. Similar results were not observed when fibroblast cultures were treated with the laser alone. These observations suggest that Q-switch II dye is an effective chemosensitizing agent for the Nd:YAG laser and could potentially be used to reduce collagen deposits in conditions such as keloids and hypertrophic scars.
Asunto(s)
Benzopiranos/farmacología , Colorantes Fluorescentes/farmacología , Terapia por Láser , Fotoquimioterapia/métodos , Supervivencia Celular , Células Cultivadas , Fibroblastos/citología , Humanos , Técnicas In VitroRESUMEN
Kodak Q-switch II is a new chemical with an absorption maxima at 1,051 nm, designed to be used as an Nd:YAG dye laser. The potential for this dye as a new chemosensitizing agent in the treatment of connective tissue diseases and wound healing with low energy Nd:YAG laser was examined. Two normal fibroblast cell lines were tested for sensitivity to various levels of this dye in vitro. These cells were exposed to Q-switch II dye at concentrations of 0.01, 0.1, 1, 10, 50, and 100 micrograms/ml for 1 and 24 hours. Cell viability was assessed by the trypan blue exclusion test. Cell duplication and DNA synthesis were measured by the incorporation of [3H]-thymidine at 6 and 24 hours postexposure to Q-switch II dye. At concentrations up to 10 micrograms/ml, both cell lines tested showed no changes in cell viability. However, at concentrations equal or higher than 50 micrograms/ml, more than 40% of the fibroblasts incorporated trypan blue after 24 hours of exposure to this dye, indicating significant cell destruction. The results indicate that Q-switch II dye is nontoxic to normal human fibroblast cultures and showed significant biostimulative effects on cell duplication at concentrations equal to or lower than 10 micrograms/ml. Further studies will be required to determine the usefulness of Q-switch II dye as a new photochemosensitizing agent for potential biostimulation of wound healing and/or treatment of connective tissue diseases with the Nd:YAG laser (near infrared, 1,060 nm) at "nonthermal" levels of energies.
Asunto(s)
Benzopiranos/farmacología , Terapia por Láser , Fármacos Sensibilizantes a Radiaciones/farmacología , Piel/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Fenómenos Químicos , Química , ADN/biosíntesis , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Humanos , Concentración Osmolar , Piel/citología , Piel/metabolismo , Factores de TiempoRESUMEN
A human squamous carcinoma cell line (P3) was first exposed to a nontoxic dose of Rhodamine-123 (1 microgram/ml for 1 hour), then subjected to treatment with a single mode argon laser at 514.5 nm. The temperature and energy levels delivered to the target cells were determined by a reproducible method of dosimetry. Cell viability was assessed by the trypan blue exclusion test. Cell duplication and DNA synthesis were measured by the incorporation of 3H-thymidine at 6 and 24 hours post-treatment. The results indicate that Rhodamine-123 at nontoxic doses of 1 microgram/ml enhanced the tumoricidal effects of the argon laser at reduced temperatures as low as 40 degrees C. Furthermore, at physiological temperature ranges as low as 28 to 39 degrees C, an immediate and/or delayed inhibition of cell duplication was demonstrated, while cell viability was not affected. These observations, suggest that Rhodamine-123 can be used effectively as a chemosensitizing agent in the treatment of human tumor cells with the argon laser at 514.5 nm. This new technique of tumor cell targeting by Rhodamine sensitization and specific laser treatment may offer real advantages without the extreme photosensitivity associated with hematoporphyrin derivatives.
Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Rodaminas/uso terapéutico , Xantenos/uso terapéutico , Carcinoma de Células Escamosas/patología , Línea Celular , Supervivencia Celular/efectos de los fármacos , ADN de Neoplasias/biosíntesis , Humanos , Rodamina 123RESUMEN
The human squamous carcinoma cell line P3 was subjected to treatment with a single mode argon laser at 514.5 nm. The temperature and energy levels delivered to the target cells were determined by a reproducible method of dosimetry. At energy levels between 860 to 990 J/cm2 and a corresponding temperature of 39 +/- 1 degrees C, a significant delayed stimulation in DNA synthesis was noted after 24 hours, but the cells remained viable. However, at energy levels and temperatures higher or equal to 1100 J/cm2 (41 degrees C), an immediate suppression of DNA synthesis was accompanied by nonviability of the P3 carcinoma cells. These results indicate that the argon laser has potential for selective biostimulation on carcinoma cell duplication at the specific "non-thermal" range of 39 +/- 1 degrees C. Similar effects were not observed when the P3 carcinoma cells were heated to this same temperature using a standard heat bath. This phenomenon appears to represent a previously undescribed potential iatrogenic effect of the monochromatic laser beam in the treatment of cancer.
Asunto(s)
Carcinoma de Células Escamosas/patología , ADN de Neoplasias/biosíntesis , Rayos Láser/efectos adversos , Carcinoma de Células Escamosas/metabolismo , Línea Celular , Supervivencia Celular/efectos de la radiación , Humanos , Terapia por Láser , Dosis de Radiación , TemperaturaRESUMEN
Laser photodynamic therapy of superficial malignancies is a promising new approach that will become clinically useful when fluorochromes with high tumor specificity and low toxicity to normal tissues are identified. We recently reported that the mitochondrial dye, Rhodamine-123 (Rh-123), at nontoxic doses, is an effective sensitizing agent for argon laser treatment of human squamous carcinoma and melanoma cells in vitro. We now report the complete inhibition of in vivo tumor development by human M24 melanoma cells transplanted subcutaneously into nu/nu mice after exposure to 1 microgram/ml of Rh-123 for 1 hour and treatment with an argon laser at nonthermal temperatures of 36 to 40 degrees C. Significant in vivo growth was observed for all control tumors. These results demonstrate that Rh-123 enhances the tumoricidal effects of the argon laser at nonthermal temperatures and provides evidence that effective photodynamic therapy may be possible in vivo with the new fluorochrome Rhodamine-123.
Asunto(s)
Colorantes Fluorescentes/uso terapéutico , Melanoma/tratamiento farmacológico , Fotoquimioterapia , Rodaminas/uso terapéutico , Neoplasias Cutáneas/tratamiento farmacológico , Xantenos/uso terapéutico , Animales , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Técnicas In Vitro , Terapia por Láser , Ratones , Ratones Desnudos , Trasplante de Neoplasias , Rodamina 123RESUMEN
Recent studies demonstrated that the cationic, mitochondrial-specific dye Rhodamine-123 (Rh-123), is an efficient tumor photosensitizer for Argon laser treatment of human cancer cells both in vitro and in tumors grown as xenografts in athymic mice. To demonstrate the photodynamic mechanism of action of this reaction, the intracellular role of oxygen and temperature changes in treated cells have to be defined. In the current study, a large panel of human tumor cell lines of diverse histologic origin were tested for in vitro sensitivity to Rh-123 and the Argon laser (514.5 nm) in oxygen, deuterium oxide (D2O), and nitrogen (N2) environment. Tumor cells in suspension were first sensitized to Rh-123 (1 or 20 micrograms/ml for 1 hour), cooled on ice to 4 degrees C, and then exposed to the Argon laser (delta T = 14 +/- 1 degree C). Cell proliferation measured by [3H]-thymidine uptake 24 hours after sensitization with Rh-123 and laser treatment was significantly decreased in tumor cells kept in oxygen and D2O atmospheres. No decrease in DNA synthesis was seen in Rh-123 and laser treated cells kept in an N2 environment. Control tumor cells treated with Rh-123 or the Argon laser separately did not show any decreased [3H]-thymidine uptake in oxygen, D2O or N2 environment. These results provide evidence of a photodynamic process since Rh-123 sensitization and Argon laser activation occur at nonthermal levels of energy and are oxygen dependent. The high effectiveness of this technique of photodynamic therapy with the Argon laser, and low toxicity of Rh-123 could make its clinical use very attractive for the treatment of superficial malignancies.
Asunto(s)
Colorantes Fluorescentes/uso terapéutico , Terapia por Láser , Fotoquimioterapia , Rodaminas/uso terapéutico , Xantenos/uso terapéutico , Deuterio , Óxido de Deuterio , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Humanos , Técnicas In Vitro , Nitrógeno , Oxígeno/fisiología , Rodamina 123 , Células Tumorales Cultivadas , AguaRESUMEN
Rhodamine-123 uptake and release was determined in nu/nu mice heterotransplanted with P3 human squamous carcinomas to assess its value as an in vivo laser photosensitizer for treatment of solid tumors. Following intraperitoneal injection of Rh-123 (1 micrograms/g of body weight), mice were killed at 2, 4, 6 and 24 hours, and 3 and 7 days postinjection. The peak concentrations of Rh-123 per milligram of tissue measured by fluorescence spectrophotometry was distributed as follows: kidneys greater than spleen greater than intestine greater than stomach greater than liver greater than tumor greater than skin greater than skeletal muscles greater than lung greater than heart greater than blood greater than brain. No preferential uptake or retention of Rh-123 by tumors was observed. However, a longer retention with higher concentrations of the dye was seen in normal skin as opposed to P3 tumors from 4 hours to 7 days postinjection with Rh-123. The elimination of Rh-123 was rapid, with the dye falling to less than 2% of peak concentration at 7 days postinjection. Knowledge of Rh-123 biodistribution in tumors and other tissues suggests that optimal timing after injection of this dye may allow selective photodiagnosis and photodynamic therapy of tumors with the argon laser.
Asunto(s)
Carcinoma de Células Escamosas/metabolismo , Colorantes Fluorescentes/farmacocinética , Rodaminas/farmacocinética , Animales , Carcinoma de Células Escamosas/patología , Mucosa Gástrica/metabolismo , Humanos , Mucosa Intestinal/metabolismo , Riñón/metabolismo , Hígado/metabolismo , Pulmón/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Músculos/metabolismo , Trasplante de Neoplasias , Rodamina 123 , Piel/metabolismo , Espectrometría de Fluorescencia , Bazo/metabolismo , Distribución Tisular , Trasplante Heterólogo , Células Tumorales CultivadasRESUMEN
The mitochondrial dye Rhodamine 123 (Rh-123) has been shown to be an effective photosensitizer for argon-laser irradiation of some types of human cancer cells in vitro. We reported that 514.5-nm laser illumination of Rh-123 sensitized human melanoma, and squamous carcinoma cells strongly inhibited tumor-cell proliferation as measured by decreased 3H-thymidine (3H-T) uptake in vitro and may eradicate some tumors when grown as transplants in nude mice. However, several other human tumors were resistant to Rh-123 laser therapy in vitro and in vivo. In the current study, it was possible to obtain 100- to 1000-fold increased sensitivity to 514.5-nm laser illumination by replacement of Rh-123 with the cationic rhodamine dyes Rh-3G and Rh-6G. Cell viability was decreased over 95% and 3H-T incorporation reduced at least 80% by laser phototherapy after sensitizing tumor cells with 1 micrograms/mL Rh-123, 0.01 microgram/mL Rh-3G, or 0.001 microgram/mL Rh-6G. However, Rh-123 alone did not decrease 3H-T uptake significantly unless present at over 10- to 100-fold higher levels than Rh-3G, respectively. The tumor cell dye uptake level was measured by N-butanol extraction and absorption scans at 400 to 600 nm. The results revealed that dye uptake was more rapid, and retention of Rh-3G and Rh-6G was 5- to 10-fold higher than for Rh-123 in the human tumor cells. The data suggest that Rh-3G and Rh-6G may be highly sensitive chromophores for laser phototherapy of human cancer cells.
Asunto(s)
Antineoplásicos/uso terapéutico , Colorantes Fluorescentes/uso terapéutico , Terapia por Láser , Neoplasias/tratamiento farmacológico , Fotoquimioterapia/métodos , Rodaminas/uso terapéutico , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/metabolismo , Antineoplásicos/química , Antineoplásicos/metabolismo , Carcinoma/tratamiento farmacológico , Carcinoma/metabolismo , División Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , ADN de Neoplasias/biosíntesis , Relación Dosis-Respuesta en la Radiación , Colorantes Fluorescentes/química , Colorantes Fluorescentes/metabolismo , Calor , Humanos , Meduloblastoma/tratamiento farmacológico , Meduloblastoma/metabolismo , Neoplasias/patología , Rodamina 123 , Rodaminas/química , Rodaminas/metabolismo , Células Tumorales CultivadasRESUMEN
Previous studies have shown that Rhodamine 123 (Rh123) is an efficient tumor targeting agent for argon laser photodynamic therapy in vitro. Effectiveness of this approach for cancer treatment in vivo will depend on Rh123 tumor uptake kinetics and laser energy delivery via fiberoptics to the tumor site. In the present study, tumor and normal cells were exposed in vitro to 1 micrograms/mL Rh123 until 10%, 50%, and 100% of maximum uptake was achieved. Laser treatment response was monitored by trypan blue exclusion for tumor cell viability and by MTT tetrazolium assays to measure mitochondrial dehydrogenase activity. TE671 fibrosarcoma cells were highly sensitive to argon laser phototherapy (514 nm, 5 W, 1 minute, Tmax = 8 degrees C), with mitochondrial inhibition seen after Rh123 uptake of 12, 50, and 100 ng/million cells. P3 squamous cell carcinoma cells were inhibited 20% and 75% by the laser after Rh123 uptake of 13 or 30 ng/million cells, respectively. M26 melanoma cells were not sensitive to the laser after 15 ng/million cells Rh123 uptake but were inhibited 45% and 75% after Rh123 uptake of 80 and 160 ng/million cells. Micro2 fibroblast mitochondrial activity was reduced less than 25% by the laser after Rh123 uptake of 50 ng/million cells. Cell viability after maximum Rh123 uptake and laser treatment was decreased to 30%, 15%, and 2% for M26 melanoma, P3 squamous cell carcinoma, and TE671 fibrosarcoma cells, but remained over 80% for Micro2 fibroblasts. The results suggest that Rh123 laser treatment response depends on tumor type and drug uptake level, with normal cells being much less sensitive to phototherapy.
Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Colorantes Fluorescentes/uso terapéutico , Terapia por Láser , Neoplasias/tratamiento farmacológico , Fotoquimioterapia , Rodaminas/uso terapéutico , Antimetabolitos Antineoplásicos/farmacocinética , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/metabolismo , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Relación Dosis-Respuesta a Droga , Relación Dosis-Respuesta en la Radiación , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Fibrosarcoma/tratamiento farmacológico , Fibrosarcoma/metabolismo , Colorantes Fluorescentes/farmacocinética , Humanos , Melanoma/tratamiento farmacológico , Melanoma/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Neoplasias/metabolismo , Rodamina 123 , Rodaminas/farmacocinética , Sales de Tetrazolio , Células Tumorales CultivadasRESUMEN
The search for improved photosensitizers for laser phototherapy of malignancies has led to the examination of a new group of carbocyanine dyes as effective fluorochromes. In this study, four carbocyanine dyes with different absorption maxima of 483 nm [DiOC6(3)], 545.5 nm (DiIC5(3)], 556.6 nm [DiSC5(3)], and 651.0 nm [DiSC3(5)] were tested in vitro. The kinetics of uptake and toxicity of these four dyes were assessed for P3 human squamous cell carcinoma, HT29 colon carcinoma, M26 melanoma, and TE671 fibrosarcoma cell lines at 15, 30, 45, 60, and 180 minutes after exposure with each dye. After sensitization with DiOC6(3), the P3 and M26 cell lines were also tested for phototherapy by treatment with 488-nm light from an argon laser. The results showed that these four carbocyanine dyes had rapid and significant uptake by the carcinoma cell lines with no toxicity at concentrations < 0.1 micrograms/mL. Nontoxic DiOC6(3) levels in sensitized tumor cells after laser phototherapy resulted in approximately 85% inhibition of P3 and approximately 95% inhibition of M26 cell lines by MTT assays. The results suggest that these carbocyanine dyes can be used for tumor photosensitization and wavelength-matched laser photodynamic therapy. Further in vivo studies will be necessary to define the clinical potential of carbocyanine dyes as tumor-targeting agents for phototherapy of cancer.
Asunto(s)
Carbocianinas/uso terapéutico , Colorantes Fluorescentes/uso terapéutico , Terapia por Láser , Neoplasias/tratamiento farmacológico , Fotoquimioterapia , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/metabolismo , Argón , Benzotiazoles , Carbocianinas/farmacocinética , Carbocianinas/farmacología , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/metabolismo , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/metabolismo , Fibrosarcoma/tratamiento farmacológico , Fibrosarcoma/metabolismo , Colorantes Fluorescentes/farmacocinética , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Meduloblastoma/tratamiento farmacológico , Meduloblastoma/metabolismo , Melanoma/tratamiento farmacológico , Neoplasias/metabolismo , Sales de Tetrazolio , Células Tumorales CultivadasRESUMEN
A new and highly promising adjunctive modality for the diagnosis and therapy of malignancies is under development using lasers and tumor targeting dyes. To reach the eventual goal of clinical treatment, several current "fantasies and fallacies" regarding laser applications in medicine must be identified and their problems clearly outlined. A multidisciplinary scientific approach is also required to enable the clinical practicality of this laser targeting approach. Many new dyes and laser wavelengths are being tested to improve specific tumor uptake and/or retention, lower systemic toxicity, increase tissue penetration, and identify fluorochromes with synergistic properties to further enhance laser tumoricidal effects. Rapid technological advancements in magnetic resonance imaging may now provide an extremely sensitive way to detect and monitor laser-tissue effects, and allow efficient interstitial laser phototherapy of deep and sometimes inaccessible tumors. The current and future prospectives of the emerging field of laser phototherapy are described.
Asunto(s)
Terapia por Láser , Neoplasias/tratamiento farmacológico , Fotoquimioterapia/métodos , Colorantes , Humanos , Rayos Láser , Neoplasias/diagnóstico , Fotoquimioterapia/tendenciasRESUMEN
Rhodamine-123 (Rh-123) has been tested recently as a new laser dye for photodynamic therapy of human tumors in vitro and in vivo. Prior to initiation of clinical studies of this technique, we evaluated the biodistribution, metabolism, and pathological changes of Rh-123 in rabbits after systemic, repetitive injections of the dye in escalating doses. At doses between 0.1 to 1 mg/kg of Rh-123 injected intramuscularly (IM) daily for 5 days, no local or systemic toxicity was observed during the 4 weeks of follow-up. The peak concentrations of Rh-123 in micrograms/g of tissue was distributed as follows: kidney (3.24) greater than heart (2.24) greater than spleen (1.77) greater than lung (0.61) greater than liver (0.38) greater than skin (0.30) greater than skeletal muscle (0.17) greater than genitals (0.13) greater than brain (0.04). The elimination of Rh-123 was very rapid, with the dye falling to 2.7% of peak concentration at 72 hours in the kidneys, and to undetectable levels at 240 hours postinjection in all organs, except the skin, which retained 3% of the peak level at 240 hours. The low toxicity and rapid metabolism of Rh-123 in this preclinical model suggests that the dye and Argon laser may represent an effective combination for treatment of superficial malignancies.
Asunto(s)
Colorantes/uso terapéutico , Fotoquimioterapia/métodos , Rodaminas/uso terapéutico , Animales , Peso Corporal/efectos de los fármacos , Colorantes/farmacocinética , Evaluación Preclínica de Medicamentos , Femenino , Corazón/efectos de los fármacos , Riñón/efectos de los fármacos , Riñón/metabolismo , Masculino , Miocardio/metabolismo , Conejos , Rodamina 123 , Rodaminas/farmacocinética , Bazo/metabolismo , Distribución TisularRESUMEN
Rhodamine-123 (Rh-123) is a mitochondrial-specific dye that has recently proven to be an effective fluorochrome for photo-dynamic therapy of squamous carcinoma cells and melanomas with the Argon laser. Complete eradication of heterotransplanted human tumors in nude mice was possible if tumors were first "sensitized" to Rh-123 and then treated with the Argon laser. Prior to initiation of human testing of this technique, the toxicity and pathological changes in BALB/c mice were tested by an escalating dose schedule after systemic injection of Rh-123. Animals' body weight, blood chemistry, enzymes and organ evaluation for histology, and ultrastructural changes were analyzed for 3 weeks after injection with Rh-123. The results of this study demonstrate that Rh-123 has significant systemic toxicity in BALB/c mice injected at doses of 10 micrograms/g of body weight and above, manifested by chronic weight loss and elevation of muscle enzymes with death of the animals injected at doses higher than 50 micrograms/g of body weight. At doses of 1 micrograms/g of Rh-123, no local or systemic toxicity was observed even after a 3-week follow-up, suggesting that safe and effective tumor sensitization might be possible in humans at this concentration. The high effectiveness of this new technique of photodynamic therapy and the low toxicity of this dye in this preclinical model system suggests that Rh-123 and the Argon laser may represent a powerful new method for treatment of superficial malignancies.
Asunto(s)
Antineoplásicos/toxicidad , Colorantes Fluorescentes/toxicidad , Rodaminas/toxicidad , Xantenos/toxicidad , Animales , Relación Dosis-Respuesta a Droga , Masculino , Ratones , Ratones Endogámicos BALB C , Fotoquimioterapia , Rodamina 123 , Pérdida de Peso/efectos de los fármacosRESUMEN
The rapid technological advances of magnetic resonance imaging, laser fiberoptics, and compatible probes may allow treatment of deep and sometimes surgically unreachable tumors of the head and neck with minimal morbidity through interstitial laser phototherapy. In this study, a new application of magnetic resonance imaging was developed to monitor and quantify laser-induced tissue damages. Pig skin was exposed to increased levels of argon laser (514.5 nm) at energy densities between 62.5 and 375 J/cm2 as determined by an accurate and reproducible method of dosimetry. Thermal profiles were recorded using an infrared sensor and T1- and T2-weighted magnetic resonance images were taken; afterward, biopsies were performed to quantitate the level of tissue damage. Our results demonstrate that above a certain threshold of laser energy, the magnetic resonance imaging findings are temperature dependent. Appropriate development of a scale matching laser energies, temperature profiles, T1- and T2-weighted magnetic resonance images, and histological quantitation of tissue destruction will allow us to optimize the three-dimensional control and monitoring of laser-tissue interactions.
Asunto(s)
Rayos Láser , Imagen por Resonancia Magnética , Fototerapia , Animales , Relación Dosis-Respuesta en la Radiación , Femenino , Monitoreo Fisiológico/métodos , Piel/efectos de la radiación , PorcinosRESUMEN
Flexible Nd:YAG endoscopic laser surgery may become an effective new modality for palliation in patients with obstructive endotracheal metastatic malignancies. We report the results of the treatment of two patients with severely obstructing intraluminal tracheal metastatic melanoma and medullary thyroid carcinoma, using the neodymium-YAG laser via the flexible fiberoptic bronchoscope. Both patients complained of significant dyspnea, orthopnea, cough, and hemoptysis and were not candidates for rigid bronchoscopy because of underlying medical contraindications and anatomical problems. Multiple treatment sessions were used with treatment intervals of 1 to 2 weeks. All treatments were performed in the operating room under sedation, without intubation, with topical lidocaine and standard superior laryngeal nerve block. Successful relief of airway obstruction with complete regression of the endotracheal masses was achieved and no recurrences were seen after 9 months' follow-up. Flexible Nd:YAG laser bronchoscopy offered an alternative for the relief of obstructing endotracheal or bronchial malignancies in patients in whom the rigid bronchoscope could not be passed. it seemed to prolong survival in selected cases, and provided definite improvement in quality of life.
Asunto(s)
Terapia por Láser , Cuidados Paliativos , Neoplasias de la Tráquea/secundario , Estenosis Traqueal/cirugía , Anciano , Carcinoma/complicaciones , Carcinoma/patología , Carcinoma/secundario , Carcinoma/cirugía , Humanos , Masculino , Melanoma/complicaciones , Melanoma/patología , Melanoma/secundario , Melanoma/cirugía , Neoplasias Nasales/patología , Neoplasias de la Tiroides/patología , Neoplasias de la Tráquea/complicaciones , Neoplasias de la Tráquea/patología , Neoplasias de la Tráquea/cirugía , Estenosis Traqueal/etiología , Estenosis Traqueal/patologíaRESUMEN
Interstitial laser phototherapy (ILP) is a promising technique in which laser energy is delivered percutaneously to various depths of tumors. This technique will become clinically useful only when efficient, sensitive, and noninvasive monitoring systems are developed. In this study, the spatial distribution of ILP in bovine liver tissue, induced by a Nd: YAG laser with an interstitial sapphire-frosted contact probe, was evaluated by magnetic resonance imaging (MRI). Tissue was exposed to three energy densities of the Nd:YAG laser by a reproducible method of dosimetry. Thermal profiles were measured with a probe inserted 5 mm from the laser tip. T1-weighted magnetic resonance images were taken after the laser exposure. Tissue specimens were then evaluated for standard quantification of laser-induced damages. A linear correlation between the level of laser energy, induced temperature change, lesion size on T1 magnetic resonance image, and volume of histological damage was observed. Further improvement of this technique of dosimetry in an in vivo model should allow the development of software for MRI which will correlate the above parameters and render this technique of ILP clinically useful.
Asunto(s)
Terapia por Láser , Hígado/efectos de la radiación , Imagen por Resonancia Magnética , Fototerapia/métodos , Animales , Bovinos , Dosis de RadiaciónRESUMEN
Interstitial laser phototherapy (ILP) guided by magnetic resonance imaging (MRI) may become an attractive adjunctive modality for the treatment of deep and surgically inaccessible tumors of the head and neck when accurate methods of laser dosimetry and "real-time" monitoring techniques with the MRI are introduced. We recently demonstrated in ex vivo and in vivo models, a linear relationship between levels of laser energies, thermal profiles, MR signal intensity changes, and histopathological tissue damage. Results of treatment in a patient with an unresectable large right jugulodigastric metastatic squamous carcinoma using new approach of MRI guided ILP are now reported. The patient complained of significant right-sided neck pain and headaches secondary to a rapidly growing metastatic lymphadenopathy which recurred after previous surgery, radiation, and chemotherapy. Two treatment sessions were used at an interval of 2 weeks. Each treatment was performed in the MRI suite under heavy sedation. Using a 600-microns bare fiber of the Nd:YAG laser implanted interstitially under MR guidance, the metastatic node was treated at three sites. T1- and T2-weighted images were performed prior to, immediately after, 24 and 48 hours, and 4, 5, 7, 9, 16, and 25 days post-treatment. Successful relief of pain and growth arrest of this node was observed after the second treatment and at the 3-month follow-up. These results demonstrate that this technique of ILP guided by MRI may be feasible in humans, and will become clinically practical when appropriate methods of dosimetry and instrumentation are developed.
Asunto(s)
Carcinoma de Células Escamosas/secundario , Carcinoma de Células Escamosas/cirugía , Neoplasias de Cabeza y Cuello/secundario , Neoplasias de Cabeza y Cuello/cirugía , Neoplasias Laríngeas , Fotocoagulación/métodos , Metástasis Linfática , Imagen por Resonancia Magnética , Silicatos de Aluminio , Cateterismo/instrumentación , Terapia Combinada , Femenino , Humanos , Fotocoagulación/instrumentación , Persona de Mediana Edad , Neodimio , Invasividad Neoplásica , Cuidados Paliativos , ItrioRESUMEN
Interstitial laser therapy (ILT) is a promising therapeutic technique in which laser energy is delivered percutaneously to various depths in tissue. In this study, the authors compared high-speed magnetic resonance imaging (MRI) of ILT in tissues during treatment with post-treatment histopathologic specimens. The use of 5-second MRI scans allowed detection of thermal damage by the 1064-nm neodymium:yttrium-aluminum-garnet laser in ex vivo liver and brain tissues. These tissues were treated by ILT with 20 W of laser output for 5 to 30 seconds via a 600-microns fiberoptic inserted 1 cm into the specimens at a power density of 7 kW/cm2 at the tip of the bare fiber. Sequential MRI measurements of lesion areas made during and after treatment were compared to measurements of laser-induced tissue damage in histopathologic sections. Fast MRI scans and tissue histology both demonstrated increased lesion size with time of ILT. Serial images obtained during ILT detected thermal changes as areas of low signal intensity that exceeded the size of the post-treatment lesions as measured on either final MRI or histology. The thermal effects detectable by these high-speed MRI sequences can be used to monitor laser-induced tissue changes during therapy, thereby providing a valuable noninvasive method for the intraoperative assessment of heat distribution during ILT.
Asunto(s)
Terapia por Láser/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Animales , Encéfalo/patología , Encéfalo/cirugía , Hígado/patología , Hígado/cirugía , Imagen por Resonancia Magnética/métodos , OvinosRESUMEN
OBJECTIVE: Interstitial laser therapy (ILT) with the neodymium:yttrium-aluminum-garnet (Nd:YAG) (1064 nm) laser via fiberoptics is becoming a more precise, minimally invasive alternative for thermoablation of unresectable or recurrent head and neck neoplasms, but recurrence is often seen at the margin. Combining intratumor chemotherapy with interstitial laser should be most effective using drugs activated by thermal energy. The objective of the current study was to test intratumor cisplatinum (cis-diaminedichloroplatinum [CDDP]) injections given in conjunction with laser therapy as an experimental approach for improved treatment of squamous cell carcinoma (SCC). METHODS: Human SCC tumors were grown as subcutaneous transplants in nude mice and injected with CDDP (0.4 to 1.2 mg/g) in water or in collagen-based gel carrier with epinephrine (epi-gel) followed by ILT via 0.6-mm fiberoptics coupled to an Nd:YAG laser (1064 nm/180 J). RESULTS: Tumors injected with CDDP epi-gel exhibited a partial response with two- to fourfold tumor delay compared with aqueous drug or untreated SCC transplants during 10 weeks' follow-up. Combined drug and laser therapy significantly (P < .01) decreased tumor volume, with recurrence in only 25% of animals tested compared with 78% tumor regrowth after ILT alone. CONCLUSION: These initial results suggest that laser chemotherapy may become an effective treatment for advanced head and neck cancer.