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obJect. The purpose of this study was to evaluate the role of stereotactic radiosurgery (SRS) in the management of intracranial hemangioblastomas. methods. Six participating centers of the North American Gamma Knife Consortium and 13 Japanese Gamma Knife centers identified 186 patients with 517 hemangioblastomas who underwent SRS. Eighty patients had 335 hemangioblastomas associated with von Hippel-Lindau disease (VHL) and 106 patients had 182 sporadic hemangioblastomas. The median target volume was 0.2 cm 3 (median diameter 7 mm) in patients with VHL and 0.7 cm 3 (median diameter 11 mm) in those with sporadic hemangioblastoma. The median margin dose was 18 Gy in VHL patients and 15 Gy in those with sporadic hemangioblastomas. results. At a median of 5 years (range 0.5-18 years) after treatment, 20 patients had died of intracranial disease progression and 9 patients had died of other causes. The overall survival after SRS was 94% at 3 years, 90% at 5 years, and 74% at 10 years. Factors associated with longer survival included younger age, absence of neurological symptoms, fewer tumors, and higher Karnofsky Performance Status. Thirty-three (41%) of the 80 patients with VHL developed new tumors and 17 (16%) of the106 patients with sporadic hemangioblastoma had recurrences of residual tumor from the original tumor. The 5-year rate of developing a new tumor was 43% for VHL patients, and the 5-year rate of developing a recurrence of residual tumor from the original tumor was 24% for sporadic hemangioblastoma patients. Factors associated with a reduced risk of developing a new tumor or recurrences of residual tumor from the original tumor included younger age, fewer tumors, and sporadic rather than VHL-associated hemangioblastomas. The local tumor control rate for treated tumors was 92% at 3 years, 89% at 5 years, and 79% at 10 years. Factors associated with an improved local tumor control rate included VHL-associated hemangioblastoma, solid tumor, smaller tumor volume, and higher margin dose. Thirteen patients (7%) developed adverse radiation effects (ARE) after SRS, and one of these patients died due to ARE.

Present evidence suggests that a majority of murine CD3+ intraepithelial intestinal lymphocytes (IEL) are extrathymically derived T cells and that these extrathymically derived IEL phenotypically express the CD8 homodimer (CD8 alpha alpha). Recently, CD3- IEL have been reported to express the recombination activating gene (RAG-1), suggesting that precursors to extrathymically derived CD3+CD8+ alpha alpha IEL exist on the intestinal epithelium. To study in detail whether these CD3-IEL can develop into CD3+CD8+ alpha alpha IEL, we analyzed the CD3-IEL subset and found that it can be separated into two subsets, namely CD3-CD8- and CD3-CD8+ IEL. We show that (1) CD3-CD8- IEL are mostly small, non-granular and phenotypically Pgp-1+ IL-2R+ B220-, while CD3-CD8+ IEL are mostly large, granular and phenotypically Pgp-1- IL-2R+ B220+, (2) CD(3-)-CD8+ IEL express the RAG-1 gene, and (3) CD3-CD8-, CD3-CD8+ and CD3+CD8+ alpha alpha IEL, respectively, appear sequentially in normal ontogeny and in bone marrow-reconstituted thymectomized radiation chimeras. In the latter, virtually all CD3+CD8+ alpha alpha IEL expressed the gamma delta T cell receptor (TCR), but not the alpha beta TCR. From this and what is presently known about T cell development, we propose that CD3-CD8+ IEL are an intermediate in extrathymic IEL development and that the development of extrathymically derived IEL occurs at the intestinal epithelium from CD3-CD8- to CD3-CD8+ to CD3+(gamma delta TCR)CD8+ alpha alpha.

Overwhelming evidence suggests that the majority of murine small intestinal intraepithelial lymphocytes (IEL) are extrathymically derived. These IEL include those with T cell receptor (TCR) gamma delta and some TCR alpha beta (CD8 alpha alpha and Thy-1-). In contrast, congenitally athymic nude mice have low numbers of gamma delta TCR IEL as well as very few alpha beta TCR IEL, far less than that would be expected if one assumes that gamma delta TCR IEL and alpha beta TCR (CD8 alpha alpha and Thy-1-) IEL in euthymic mice are extrathymically derived. To examine this discrepancy, we followed extrathymic IEL differentiation in IEL of day 3-thymectomized (NTX) mice as another athymic mouse model and found that gamma delta TCR IEL and extrathymically derived alpha beta TCR IEL in NTX mice are markedly reduced, almost to the level of nude mice. We further show that it is probably the absence of a thymic stroma that is responsible for the lower amounts of extrathymically derived IEL in nude mice, as the low amounts can be corrected to euthymic levels by syngeneic fetal thymus grafting but not by direct injection of F1 thymocytes. Lastly, unlike TCR/CD3+ extrathymically derived IEL, we noted a large proportion of extrathymic CD3-CD8- and CD3-CD8+ IEL; they were threefold more frequent in nude and NTX than in euthymic mice. This suggests that the thymus influences extrathymically derived IEL in its development from CD3- to CD3+ at the small intestinal epithelium.

3-D digital subtraction angiography enables the surgeon to understand the 3-D structure of lesions and is very useful in planning the surgical treatment of cerebral aneurysms.