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The factors that determine whether disseminated transformed cells in vivo yield neoplastic lesions have only been partially identified. We established an ad hoc model of peritoneal carcinomatosis by injecting colon carcinoma cells in mice. Tumor cells recruit inflammatory leukocytes, mostly macrophages, and generate neoplastic peritoneal lesions. Phagocyte depletion via clodronate treatment reduces neoplastic growth. Colon carcinoma cells release a prototypic damage-associated molecular pattern (DAMP)/alarmin, High Mobility Group Box1 (HMGB1), which attracts leukocytes. Exogenous HMGB1 accelerates leukocyte recruitment, macrophage infiltration, tumor growth and vascularization. Lentiviral-based HMGB1 knockdown or pharmacological interference with its extracellular impair macrophage recruitment and tumor growth. Our findings provide a preclinical proof of principle that strategies based on preventing HMGB1-driven recruitment of leukocytes could be used for treating peritoneal carcinomatosis.

The factors that determine whether disseminated transformed cells in vivo yield neoplastic lesions have only been partially identified. We established an ad hoc model of peritoneal carcinomatosis by injecting colon carcinoma cells in mice. Tumor cells recruit inflammatory leukocytes, mostly macrophages, and generate neoplastic peritoneal lesions. Phagocyte depletion via clodronate treatment reduces neoplastic growth. Colon carcinoma cells release a prototypic damage-associated molecular pattern (DAMP)/alarmin, High Mobility Group Box1 (HMGB1), which attracts leukocytes. Exogenous HMGB1 accelerates leukocyte recruitment, macrophage infiltration, tumor growth and vascularization. Lentiviral-based HMGB1 knockdown or pharmacological interference with its extracellular impair macrophage recruitment and tumor growth. Our findings provide a preclinical proof of principle that strategies based on preventing HMGB1-driven recruitment of leukocytes could be used for treating peritoneal carcinomatosis.

Purpose: The diagnosis of peritoneal carcinomatosis secondary to ovarian cancer is a real challenge in the cancer imaging field. In this retrospective study, we evaluate the accuracy of Single Detector Computed Tomography (SDCT), Multi Detector Computed Tomography (MDCT), and Positron Emission Tomography-Computed Tomography with F18-fluorodeoxyglucose ([ 18F]FDG-PET/CT) in the diagnosis of peritoneal seeding and we evaluate the possible applications of MDCT to predict the complete surgical removal of the peritoneal deposits. Methods and materials: A total of 228 scans (91 SDCT, 89 MDCT, and 48 [18F]FDG-PET/CT) of patients with peritoneal carcinomatosis secondary to ovarian cancer proved at laparoscopy and confirmed by histopathology were retrospectively reviewed by two independent groups of Radiologists and Nuclear Medicine Physicians for the evaluation of ascites, peritoneal nodules, and omental cake signs. Results: MDCT showed 81% of true positives, SDCT 72.5%, and [18F]FDG-PET/CT 77%. False negatives were 19% for MDCT, 27.5% for SDCT, and 23% for [18F]FDG-PET/CT. Conclusion: From our results, we concluded that MDCT is the technique of choice in the diagnosis of peritoneal seeding, while [18F]FDG-PET/CT, though showing similar accuracy, remains the most accurate technique for monitoring therapeutic response and disease recurrence. MDCT could play an important role due to its ability to predict the possibility of complete surgical removal of disease thus influencing the treatment plan aimed to improve quality of life. © Springer Science+Business Media, LLC 2009.