Laser ablation of the biliary tree: in vivo proof of concept as potential treatment of unresectable cholangiocarcinoma.

OBJECTIVES: The palliative treatment of cholangiocarcinoma is based on stent placement with well-known procedure-related complications. Consequently, alternative energy-based techniques were put forward with controversial long-term results. This study aims to evaluate the safety and effectiveness of biliary tree laser ablation (LA) in terms of: (i) absence of perforation, (ii) temperature increase, (iii) induced thermal damage in in vivo models. MATERIALS AND METHODS: The common bile duct and cystic ducts of two pigs were ablated with a diode laser (circumferential irradiation pattern) for 6 and 3 min at 7 W. Laser settings were chosen from previous ex vivo experiments. Local temperature was monitored through a fibre Bragg grating (FBG) sensor embedded into the laser delivery probe. Histopathological analysis of the ablated specimen was performed through in situ endomicroscopy, haematoxylin and eosin (H&E) and nicotinamide adenine dinucleotide (NADH) stains. RESULTS: Temperature reached a plateau of 53 °C with consequent thermal damage on the application area, regardless of laser settings and application sites. No perforation was detected macroscopically or microscopically. At the H&E stain, wall integrity was always preserved. The NADH stain allowed to evaluate damage extension. It turned out that the ablation spreading width depended on application time and duct diameter. In situ endomicroscopy revealed a clear distinction between ablated and non-ablated areas. CONCLUSIONS: The temperature distribution obtained through LA proved to induce a safe and effective intraductal coagulative necrosis of biliary ducts. These results represent the basis for further experiments on tumour-bearing models for the treatment of obstructive cholangiocarcinoma.

Pro- and anti-oxidant properties of near-infrared (NIR) light responsive carbon nanoparticles.

Elemental carbon nanomaterials (ECNMs) are redox active agents that can be exploited to purposely modify the redox balance of cells. Both pro- or antioxidant properties have been reported. However, to the best of our knowledge, there are not comprehensive studies exploring both properties on the same material in view of a potential application in medicine. At the same time, the effect of the bulk structure on the pro/antioxidant properties is poorly known. Here, carbon nanoparticles (CNPs) derived by glucose with definite size and shape have been prepared, and their redox properties evaluated in cell free systems in the dark or following activation with a Near Infrared (NIR) laser beam (945 nm, 1.3 W/cm2). We found that, when irradiated with NIR, CNPs efficiently generate heat and singlet oxygen (1O2), a property that can be exploited for dual photo-thermal (PT)/photodynamic (PD) therapy in cancer. On the other hand, in the absence of photo-activation, CNPs react with both oxidant (hydroxyl radicals) and antioxidant (glutathione) species. When tested on a murine macrophages cell line (RAW 264.7) CNPs were clearly antioxidant. Furthermore, albeit efficiently internalized, CNPs do not exert cytotoxic effect up to 80 µg/ml and do not exacerbate TNF-α-mediated inflammation. Overall, the results reported herein suggest that CNPs may represent a new class of safe nanomaterials with potential applications in medicine.

Linearly chirped fiber Bragg grating response to thermal gradient: from bench tests to the real-time assessment during in vivo laser ablations of biological tissue.

The response of a fiber optic sensor [linearly chirped fiber Bragg grating (LCFBG)] to a linear thermal gradient applied on its sensing length (i.e., 1.5 cm) has been investigated. After these bench tests, we assessed their feasibility for temperature monitoring during thermal tumor treatment. In particular, we performed experiments during ex vivo laser ablation (LA) in pig liver and in vivo thermal ablation in animal models (pigs). We investigated the following: (i) the relationship between the full width at half maximum of the LCFBG spectrum and the temperature difference among the extremities of the LCFBG and (ii) the relationship between the mean spectrum wavelength and the mean temperature acting on the LCFBG sensing area. These relationships showed a linear trend during both bench tests and LA in animal models. Thermal sensitivity was significant although different values were found with regards to bench tests and animal experiments. The linear trend and significant sensitivity allow hypothesizing a future use of this kind of sensor to monitor both temperature gradient and mean temperature within a tissue undergoing thermal treatment.