An angiogenic response originating from peritumoral sinusoids and portal tracts that leads to the formation of metastases with sinusoidal-and portal-type angiogenic patterns, respectively, occurs during the course of liver colonization by murine 51b colon carcinoma (51b-CC) cells. We found a 5-fold increase in endogenous endostatin levels from hepatic blood over baseline (25 ؎ 6 ng/mL) when micrometastatic foci had a detectable size and a 14-fold increase when macrometastases were developed. Despite this endogenous endostatin production, subcutaneous administration of recombinant human endostatin (rh-E; 50 mg/kg) decreased metastasis number by 60% when dosed from days 1 to 20 after 51b-CC cell injection, by 40% when given from days 10 to 20, and by 30% when administered as a single dose 30 minutes before 51b-CC cell injection compared with controls. In addition, administration of rh-E from days 10 to 20 decreased overall metastasis volume by 90% compared with controls. rh-E increased the number of necrotic sinusoidal-type metastases by 7-fold and decreased their intrametastatic CD31 ؉ -microvessel density by 80% without affecting portal-type metastases. H epatic metastasis progression 1 involves 2 key microvascular events: (1) circulating cancer cell adhesion to endothelium, which facilitates metastatic cell implantation and growth along an angiogenesis-independent prevascular stage occurring when micrometastases are smaller than 400 m in diameter, and (2) cancer cell proliferation along an angiogenesisdependent stage, which leads to clinically relevant macrometastatic growth. 2 The transition from preangiogenic to angiogenic micrometastasis is critical in the progression of liver metastasis. However, its underlying mechanism is unclear. In fact, despite hepatic production of endogenous angiogenesis inhibitors, 3 a strong angiogenic response during metastasis development has been reported, which evolves in 2 metastasis subtypes 4 : (1) a sinusoidal type, in which the angiogenic process primarily depends on tumor-activated sinusoidal endothelium and stellate cell recruitment, 5 and (2) a portal type, in which the angiogenic process primarily depends on tumor-activated microvessels and fibroblasts from the perilobular stroma. These 2 angiogenic patterns are also observed in human hepatic metastases from colorectal cancer, 6 but the clinical significance is unknown.Antiangiogenic compounds such as recombinant human endostatin (rh-E) 7 can greatly decrease experimental metastatic growth in the lung. 8 However, because the liver is supposed to be a major source of antiangiogenic recombinant human endostatin; HSE, hepatic sinusoidal endothelium; FSC, forward scatter; SSC, side scatter. From the

Specific genetic profiles for each group have been found. Similarities between primary tumor and second primary tumor and dissimilarity between primary tumor and recurrence suggest that clinicopathological criteria do not always accurately differentiate these entities. Genetic profiling may aid in the diagnosis and prognosis of these difficult cases.

The aim of this study was to report our experience on the management of radiation-induced sarcomas (RISs). A retrospective study from 1994 to 2003 was done at our institution reviewing the medical records of 5 patients who had RISs. Five patients diagnosed of head and neck cancer received irradiation to treat their diseases. Later on, these patients developed new neoplasms in the irradiation fields (3 malignant fibrous histiocytoma, 1 osteosarcoma, and 1 angiosarcoma). The mean period of latency between irradiation and diagnosis of new tumors was 13 years. Early symptoms included neck or face swelling, odynophagia, or trigeminal hypoesthesia. All of the patients underwent surgical treatment. In 4 cases, regional and free flaps for head and neck reconstruction were required. Three patients also needed neoadjuvant chemotherapy. In the follow-up, 2 patients are alive and free of disease. Wide excision is the treatment of choice for RISs. Previous radiation therapy limits the dose that can be administered to the involved area, and the response rate to the chemotherapy is always poor.

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