RESUMEN
This article investigates an endoscopic approach that utilizes negative pressure to achieve laser-induced thermal coagulation limited to the esophageal wall's mucosal and superficial submucosal layers. The study was built upon a series of studies combining numerical simulation based on the Monte-Carlo technique and ex vivo porcine tissue experiments, including apparatus design and histology analysis. An endoscopy apparatus was developed using 3D printing to validate the tissue stretching-based approach. A fiber-pigtailed diode was used as the near-infrared source, emitting 208.8 W/cm2 laser irradiance at 1.5 µm. Simulation results suggested that the approach successfully created a local heat well to prevent residual thermal effects (>65°C) from penetrating the deeper submucosal layer. Histology analysis of ex vivo tissues showed that at a fluence of 5.22 kJ/cm2, the depth of thermal coagulation was reduced by half compared to the control. With further preclinical studies, including endoscopy apparatus design, the approach can be applied to the larger esophageal surface.
Asunto(s)
Terapia por Láser , Animales , Porcinos , Endoscopía , Rayos Láser , Luz , FototerapiaRESUMEN
OBJECTIVES: The transfer and widespread acceptance of laser-induced thermal therapy into gastroenterology remain a topic of interest. However, a practical approach to the quantitative effect of photothermal injury in the esophagus needs further investigation. Here, we aim to perform computer simulations that simulate laser scanning and calculate the laser-induced thermal damage area. The simulation engine offers the results in a guide map for laser coagulation with a well-confined therapeutic area according to laser irradiance and surface scanning speed. The study also presents validation experiments that include histology analyses in an ex vivo sheep esophagus model. METHODS: The simulation engine was developed based on the Monte-Carlo method and the Arrhenius damage integral. The computational model mimicked laser scanning by shifting the position of the calculated heat source in the grating system along the axis to be scanned. The performance of the simulations was tested in an ex vivo sheep esophagus model at a laser wavelength of 1505 nm. Histological analysis, hematoxylin-eosin staining, light microscope imaging, and block-face scanning electron microscopy were used to assess thermal damage to the tissue model. RESULTS: The developed simulation engine estimated the photothermal coagulation area for a surface scanning speed range of 0.5-8 mm/second and laser power of up to 0.5 W at a 0.9-nm laser diameter in a tissue model with a volume of 4 × 4 × 4 mm3 . For example, the optimum laser irradiation for effective photothermal coagulation in the mucosa and superficial submucosa depths was estimated to be between 16.4 and 31.8 W/cm2 , 23.2 and 38.1 W/cm2 at 0.5 and 1 mm/second, respectively. The computational results, summarized as a guide map, were directly compared with the results of ex vivo tissue experiments. In addition, it was pointed out that the comparative theoretical and experimental data overlap significantly in terms of energy density. CONCLUSIONS: Our results suggest that the developed simulation approach could be a seed algorithm for further preclinical and clinical trials and a complementary tool to the laser-induced photothermal coagulation technique for superficial treatments in the gastrointestinal tract. In future preclinical studies, it is thought that the simulation engine can be enriched by combining it with an in vivo model for different laser wavelengths.
Asunto(s)
Terapia por Láser , Animales , Simulación por Computador , Esófago/cirugía , Coagulación con Láser , Terapia por Láser/métodos , Método de Montecarlo , OvinosRESUMEN
Breast cancer cells (BCC) and macrophages are known to interact via epidermal growth factor (EGF) produced by macrophages and colony stimulating factor-1 (CSF-1) produced by BCC. Despite contradictory findings, this interaction is perceived as a paracrine loop. Further, the underlying mechanism of interaction remains unclear. Here, we investigated interactions of BCC with macrophages in 2D and 3D. While both BCC and macrophages showed invasion/chemotaxis to fetal bovine serum, only macrophages showed chemotaxis to BCC in custom designed 3D cell-on-a-chip devices. These results were in agreement with gradient simulation results and ELISA results showing that macrophage-derived-EGF was not secreted into macrophage-conditioned-medium. Live cell imaging of BCC in the presence and absence of iressa showed that macrophages but not macrophage-derived-matrix modulated adhesion and motility of BCC in 2D. 3D co-culture experiments in collagen and matrigel showed that BCC changed their multicellular organization in the presence of macrophages. In custom designed 3D co-culture cell-on-a-chip devices, macrophages promoted and reduced migration of BCC in collagen and matrigel, respectively. Furthermore, adherent but not suspended BCC endocytosed EGFR when in contact with macrophages. Collectively, our data revealed that macrophages showed chemotaxis towards BCC whereas BCC required direct contact to interact with macrophage-derived-EGF. Therefore, we propose that the interaction between cancer cells and macrophages is a paracrine-juxtacrine loop of CSF-1 and EGF, respectively.