Summary. The chick embryo was used to study the relationship between the onset of tumour neovascularization and tumour growth. Walker 256 carcinosarcoma was implanted on the chorioallantoic membrane (CAM) of about 600 embryos aged 5-16 days. Tumour diameter and changes in the CAM vasculature in response to the implants were recorded daily. Representative tumours were examined by light microscopy of Epon-embedded tissue and autoradiography after injection of [3H]-thymidine. Tumours remained avascular for 72 h, after which they were penetrated by new blood vessels and began a phase of rapid growth. The rate of growth during this vascular phase was greatest for implants on 5-and 6-day-old embryos and decreased the later the day of implantation.The time of onset of tumour angiogenesis appears to be independent of the immunological state of the chick embryo, although the rate of growth after vascularization may be modified by the onset of immunity. This study suggests that the avascular and vascular phases of tumour growth are separable, and that the avascular tumour population lives under the growth constraints which limit the size of a tumour spheroid growing in soft agar or aqueous humour.THE GROWTH of tumours in vivo has been postulated to occur in two distinct phases (Folkman, 1974): an initial avascular phase characterized by slow growth, during which nutrients and wastes are transported by diffusion, followed by a phase of rapid growth, in which the tumour has become vascularized. In order to study this phenomenon we employed the chorioallantois (CAM) of the developing chick embryo as a recipient of tumour grafts, and made daily observations of graft size, state of vascularity, and response of the CAM blood vessels to the growing tumour.This study demonstrates that an avascular phase of tumour growth can be distinguished from the vascular phase by gross morphology and histology. The avascular phase is characterized by the absence of host or graft vessels within the tumour, by no visible change in the topography of the CAM blood vessels, and by slow growth for grafts less than 1 mm in diameter at implantation. The penetration of tumour by host blood vessels, followed by rapid growth, characterize the vascular phase. MATERIALS AND METHODSThe chicken embryo hatches 21 days after fertilization. The chorioallantoic men4brane emerges on Day 4 or 5 and its vessels subsequently spread over the surface of the yolk sac, totally covering it. The fertilized white Leghorn eggs (Spafas, Norwich, Connecticut) used in this study, were kept in an egg incubator at 37°C with 60% relative humidity. Before use, the section of the shell to be opened was wiped with Betadine (providone-iodine, Purdue Frederick Co., Norwalk, Connecticut) solution and allowed to air-dry at room temperature.Preparation of tumour implants.-Subcutaneous nodules of Walker 256 carcino-

The clinical and pathologic features of 254 teratomas from 245 patients are reviewed. All patients were 21 years of age or younger and were treated at the Children's Hospital Medical Center from 1928 to 1982. Tumors arose in the following anatomic sites: sacrococcygeal (102), ovary (94), head and neck (14), retroperitoneum (12), mediastinum (11), testes (eight), central nervous system (nine), liver (two), abdominal wall, and back (one each). One hundred twenty-four tumors (49%) were detected in the newborn period. Teratomas characteristically contained elements derived from all three embryonic germ layers. Tumors with any recognizable component of embryonal carcinoma or other malignant germ cell elements at the time of initial surgery were excluded. Immature teratomas were significantly larger than mature tumors in nearly all sites where statistical analysis was possible. The single most important factor affecting prognosis was whether the tumor could be resected successfully at initial surgery. No patient who did not undergo surgery, or in whom only partial resection was possible, survived the disease--regardless of other treatments used. Based upon the experience reported here the authors conclude: 1) complete surgical resection is the treatment of choice for all childhood teratomas; and 2) this is one of the few childhood tumors where decisions regarding adjuvant therapy must be individualized, particularly with regard to site of origin and age of the patient.

Between 1972 and 1981, 93 patients with extremity osteogenic sarcoma without detectable metastatic disease were treated with surgery and adjuvant chemotherapy. Fifty-two patients remain continuously free of disease. Thirty-two of the 41 patients who relapsed had pulmonary metastases only and 26 underwent thoracotomy to remove all metastatic disease. Complete resection was possible in 11 of 26 patients as defined by the removal of all macroscopic disease, no microscopic disease at resection margins, and no histologic evidence of pleural disruption by tumor. Nine of 11 patients are currently free of disease with a median duration of most recent remission of 42 months (range, 3-72 months). Four of these nine patients have had only one relapse. Only two of 15 patients with incomplete resection of metastatic disease defined by the above criteria are currently free of disease for 57 and 101 months. A significant difference in survival from initial relapse for patients made surgically free of disease using this stringent criteria was observed even when the result is stratified for time to first relapse and number of pulmonary nodules (p = 0.005). A subgroup of patients within the group undergoing thoracotomies who can be expected to have an improved survival has been defined.

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