The surgical management of peritoneal metastases, whatever their origin, raises the problem of the potential involvement of the entire peritoneal serosa. Peritoneal metastases are surface lesions, sometimes numerous, extensive, and they may be theoretically accessible to photodynamic therapy (PDT). Intraperitoneal applications of PDT are limited by the photosensitizers lack of specificity, that should explain side effects and complications observed in the past, and by the difficulties to bring light into the cavity. Past clinical evaluations had demonstrated the risks associated with this technique (capillary leak syndrome, anastomotic leakages), and no trial evaluating PDT for peritoneal metastases treatment was published since 2006.
Recent data may contribute to give a new breath for this technique. Indeed, new targeted molecules are being developed, and the optimization of illumination systems makes possible the implementation of PDT by minimally invasive approaches (laparoscopy). Immunotherapy also brings new arguments to promote PDT in this indication. Indeed, it is unrealistic to think that surgery alone can ensure satisfactory microscopic cytoreduction quality and the application of light uniformly over the whole peritoneal surface cannot be reasonably considered. Thus, the expected abscopal effect of PDT could enhance a systemic immune response leading to better control of residual lesions on the one hand, and also peritoneal and tissue recurrences at a distance.
The objective of this review is to present the most recent data and possible approaches for the treatment of peritoneal carcinomatosis by PDT.
Whether preclinical studies either involve a cell or animal model, the distribution of light plays a determinant role in the reproducibility of results of photodynamic therapy (PDT) studies. Unfortunately, only few illumination devices dedicated to preclinical studies are available and are for the most, very expensive. Most research teams use home-made solutions that may not always be reproducible because of undefined light distribution, additive thermal emission, or unsuitable for shapes and volumes to illuminate. To address these issues, we developed illumination devices dedicated to our preclinical studies, which embed knitted light emitting fabrics (LEF) technology. LEF technology offers a homogeneous light distribution, without thermal emission and can be coupled with various light sources allowing investigation of several PDT modalities (irradiance, wavelength, illumination duration/mode). For in-vitro studies, we designed light plates, each allowing illumination of up to four 96-cells plates. For in-vivo studies, we designed mice boxes allowing three animals placement in prone position, equally surrounded by LEF and ensuring homogeneous extracorporeal illumination. Optical validation was performed and reproducibility of both preclinical systems were assessed. Both systems can deliver homogeneous light with an irradiance that can reach several mW/cm2, with varying durations and wavelengths. First results of preclinical studies demonstrate a high reproducibility, with an easy setup, and a great adaptability of illumination modalities with these devices based on light emitting fabrics.