Fluorescence Imaging After Indocyanine Green Injection for Detection of Peritoneal Metastases in Patients Undergoing Cytoreductive Surgery for Peritoneal Carcinomatosis From Colorectal Cancer: A Pilot Study.

OBJECTIVE: The aim of this study was to evaluate the role of fluorescence imaging (FI) using an intraoperative injection of free indocyanine green (ICG) in the detection of peritoneal metastases (PM) due to colorectal cancer (CRC). BACKGROUND: A large proportion of patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy will have local recurrence. This is, in part, related to the presence of small undetected nodules in the peritoneal cavity. Near-infrared FI-guided surgery has provided new opportunities for detection of nonvisible lesions during cancer surgery. METHODS: Patients with PM from CRC admitted for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy were selected for participation in this study (NCT02032485). Free ICG, at 0.25 mg/kg of patient weight, was intravenous (IV)-injected intraoperatively. Tumor-to-background ratio was calculated for all suspect resected PM. RESULTS: Sixty-three of 78 peritoneal resected nodules in 14 patients were evaluated for fluorescence, among them, 53 were malignant (84%) and 10 benign (16%). Twenty-six were hypofluorescent, 16 moderately hyperfluorescent, and 21 hyperfluorescent. Amongst the 42 nodules of the 9 patients with nonmucinous adenocarcinoma, the mean tumor-to-background ratio was 1.92 (SD 0.67) in malignant and 1.02 (SD 0.06) in benign nodules (P = 0.0099). In 4 of 14 patients (29%), the surgery was modified by intraoperative ICG-FI, which detected additional PM not found using visualization and palpation. CONCLUSIONS: This pilot study demonstrates that non-mucinous PM of CRC can be visualized intraoperatively using ICG-FI. Furthermore, ICG-FI findings resulted in modification of the planned surgery in 29% of patients.

Sentinel Lymph Node Detection by Blue Dye Versus Indocyanine Green Fluorescence Imaging in Colon Cancer.

BACKGROUND/AIM: Nodal staging is used in colorectal cancer (CRC) to determine which patients should receive adjuvant chemotherapy. The aim of this study was to evaluate the role of indocyanine green fluorescence imaging (ICG-FI) in sentinel lymph node (SLN) detection compared to the standard technique. MATERIALS AND METHODS: Twenty patients with CRC admitted for elective colectomy were included (NCT01995591). Ex vivo SLN detection was performed using patent blue (PB) and free ICG injected around the tumor. RESULTS: Identification rates were 95% (19/20) for both techniques. Sensitivity was 43% for PB and 57% for ICG. Correlation between the techniques was 83%. FI was more sensitive in patients with body mass index (BMI) >25 kg/m(2) Serial section analysis did not allow for up-staging of patients. CONCLUSION: The use of ICG-FI is superior to the blue dye technique in patients with a BMI >25 kg/m(2) However, the sensitivity of ICG-FI in SLN detection remains low, with a high rate of false-negative results.

Near infrared fluorescent imaging after intravenous injection of indocyanine green during neck dissection in patients with head and neck cancer: A feasibility study.

BACKGROUND: Indocyanine green (ICG) has not been studied during therapeutic lymph node dissections after intravenous injection. The purpose of this study was to explore the distribution of ICG in lymphatic nodes during neck dissection. METHODS: Eleven patients requiring neck dissection with or without resection of the primary lesion were included. ICG was intravenously injected at induction time of anesthesia. Imaging was performed before and after surgical resection. Fluorescence was measured in arbitrary units (AUs) in the pathology department. Mixed linear model and generalized estimating equations (GEEs) were used. RESULTS: Mean fluorescence of invaded nodes was 22.6 AUs (SD = 24.9) and 3.9 AUs (SD = 8.1) in negative nodes (p = .016). After adjustment for the size of the node, the risk of invasion when fluorescence was observed was 12.2 (95% confidence interval [CI] = 5.3-28.2; p < .0001). CONCLUSION: This study demonstrates the feasibility of ICG to bring a contrast during surgery between healthy and invaded nodes after i.v. injection. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1833-E1837, 2016.

Linking antibody Fc domain to endostatin significantly improves endostatin half-life and efficacy.

PURPOSE: The half-life of the antiangiogenic molecule endostatin that has been used in clinical trial is short ( approximately 2 h). In addition, approximately 50% of the clinical grade endostatin molecules lack four amino acids at their NH(2) termini. Lack of these amino acids gives rise to a molecule that is devoid of zinc, resulting in no antitumor activity. Our goal was to develop a new version of endostatin that does not show such deficiency. EXPERIMENTAL DESIGN: A recombinant human endostatin conjugated to the Fc domain of IgG was constructed and expressed in mammalian cell culture. The presence of Fc has been shown by previous investigators to play a major role in increasing the half-life of the molecule. Fc-endostatin was tested in tumor-bearing mice, and its half-life was compared with the clinical grade endostatin. RESULTS: The antitumor dose of Fc-endostatin was found to be approximately 100 times less than the clinical grade endostatin. The half-life of Fc-endostatin in the circulation was found to be weeks rather than hours, as observed for endostatin alone. In addition, a U-shaped curve was observed for antitumor activity of endostatin as a function of endostatin concentration delivered to the animals. CONCLUSION: Fc-endostatin is a superior molecule to the original clinical endostatin. Due to its long half-life, the amount of protein required is substantially reduced compared with the clinically tested endostatin. Furthermore, in view of the U-shaped curve of efficacy observed for endostatin, we estimate that the requirement for Fc-endostatin is approximately 700-fold less than endostatin alone. The half-life of endostatin is similar to that of vascular endothelial growth factor-Trap and Avastin, two other antiangiogenic reagents. We conclude that a new clinical trial of endostatin, incorporating Fc, may benefit cancer patients.

Potentiation of photodynamic therapy with hypericin by mitomycin C in the radiation-induced fibrosarcoma-1 mouse tumor model.

Hypericin, a polycyclic quinone obtained from plants of the genus Hypericum, has been shown to be a promising photosensitizer. We investigated the combination of hypericin-photodynamic therapy (PDT) and a bioreductive drug mitomycin C (MMC) in the present study. The radiation-induced fibrosarcoma-1 tumors were exposed to laser light (120 J/cm2 at 595 nm) 24 h after an intravenous injection of hypericin (1 mg/kg). Hypericin-PDT alone significantly decreased tumor perfusion and oxygen tension as demonstrated by India ink staining technique and OxyLite pO2 measurement, respectively. The in vivo-in vitro cell-survival assay revealed about 60% direct tumor cell killing immediately after PDT. No significant delayed tumor cell death was observed after PDT, which suggests that vascular damage does not contribute significantly to the overall tumor cell death. Injection of a 2.5 mg/kg dose of MMC 20 min before light application significantly decreased tumor cell survival and delayed tumor growth compared with PDT or MMC alone. No greater skin reaction was observed after the combination of MMC and PDT than after PDT alone. Our study demonstrates that combining hypericin-PDT with MMC can be effective in enhancing tumor response with little side effect.