ABSTRACT
Objective: To conduct a systematic review of the currently available literature on the use of ICG to guide surgical dissection in gastrointestinal (GI) cancer surgery. Background: Real-time indocyanine green (ICG) fluorescence-guided surgery has the potential to enhance surgical outcomes by increasing patient-tailored oncological precision. Methods: MEDLINE, PubMed, EMBASE, and Google Scholar were searched for publications on the use of ICG as a contrast agent in GI cancer surgery until December 2020. Perfusion studies were excluded. Quality of the studies was assessed with the Methodological Index for nonrandomized Studies or Jadad scale for randomized controlled trials. A narrative synthesis of the results was provided, with descriptive statistics when appropriate. Results: Seventy-eight studies were included. ICG was used for primary tumor and metastases localization, for sentinel lymph node detection, and for lymph flow mapping. The detection rate for primary colorectal and gastric tumors was 100% after preoperative ICG endoscopic injection. For liver lesions, the detection rate after intravenous ICG infusion was 80% and up to 100% for lesions less than 8 mm from the liver surface. The detection rate for sentinel lymph nodes was 89.8% for esophageal, 98.6% for gastric, 87.4% for colorectal, and 83.3% for anal tumors, respectively. In comparative studies, ICG significantly increases the quality of D2 lymphadenectomy in oncological gastrectomy. Conclusion: The use of ICG as a guiding tool for dissection in GI surgery is promising. Further evidence from high-quality studies on larger sample sizes is needed to assess whether ICG-guided surgery may become standard of care.
ABSTRACT
Nano- and microsized extracellular vesicles (EVs) are naturally occurring cargo-bearing packages of regulatory macromolecules, and recent studies are increasingly showing that EVs are responsible for physiological intercellular communication. Nanoparticles encapsulating anti-tumor theranostics represent an attractive "exosome-interfering" strategy for cancer therapy. Methods: Herein, by labeling plasma-derived EVs with indocyanine green (ICG) and following their biodistribution by in vivo and ex vivo imaging, we demonstrate the existence of nanoparticles with a highly selective cancer tropism in the blood of colorectal cancer (CRC) patients but not in that of healthy volunteers. Results: In CRC patient-derived xenograft (PDX) mouse models, we show that transplanted EVs recognize tumors from the cognate nanoparticle-generating individual, suggesting the theranostic potential of autologous EVs encapsulating tumor-interfering molecules. In large canine breeds bearing spontaneous malignant skin and breast tumors, the same autologous EV transplantation protocol shows comparable safety and efficacy profiles. Conclusions: Our data show the existence of an untapped resource of intercellular communication present in the blood of cancer patients, which represents an efficient and highly biocompatible way to deliver molecules directly to the tumor with great precision. The novel EV-interfering approach proposed by our study may become a new research direction in the complex interplay of modern personalized cancer therapy.
