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Meningiomas, which invade intracranial bone structures and the adjacent connective tissue, are frequently unresectable because of their aggressive and recalcitrant growth behavior. They have a high recurrence rate, and in approximately 10% of these tumors there is an increased risk of malignancy. Significant morbidity and mortality rates associated with recurrent meningiomas demand nonsurgical approaches. To date, adjuvant hormonal treatment has not proven beneficial. The anticancer drug hydroxyurea was therefore tested for its potential use in the treatment of meningiomas. Early-passaged cell cultures were established from 20 different meningiomas. The addition of 5 x 10(-4) and 10(-3) M hydroxyurea over a period of 5 to 9 days resulted in a remarkable decrease in cell proliferation and even blocked tumor cell growth when compared with untreated cells. A significant arrest of meningioma cell growth in the S phase of the cell cycle was revealed on DNA flow cytometry. Electron micrographs of hydroxyurea-treated tumor cells showed ultrastructural features consistent with apoptosis, and light microscopy demonstrated DNA fragmentation by in situ DNA strand break labeling. Short-term treatment of meningioma cell cultures with hydroxyurea for 24 to 48 hours resulted in discrete oligonucleosomal fragments (DNA ladder), another characteristic sign of apoptosis. In addition to the in vitro studies, tissue from five different meningiomas was transplanted into nude mice followed by treatment with 0.5 mg/g body weight hydroxyurea over 15 days. In situ DNA strand break labeling demonstrated DNA fragmentation in distinct regions with different tumor cell densities in all hydroxyurea-treated meningioma transplants. These data provide evidence that hydroxyurea is a powerful inhibitor of meningioma cell growth, most likely by causing apoptosis in the tumor cells. Thus, hydroxyurea may be a suitable chemotherapeutic agent for the long-term treatment of unresectable or semi- to malignant meningiomas, or for preventing recurrent growth of meningiomas after resection.

Repair of aortic coarctation was performed in 152 adolescent and adult patients (mean age 28.5 years, range 14-67 years). Ninety patients were treated with patch plasty, 33 with end-to-end anastomosis, 18 with interposition of a tubular graft, 6 with prosthetic bypass and 5 with direct plasty. There were two (1.3%) early and ten (6.6%) late deaths after 2.9 to 11.8 (mean 6.6) years. Of the remaining 140 patients, 129 (92.1%) were reexamined with computed tomography and angiography after 1.5 to 17.2 (mean 9.1) years postoperatively. In 27 patients (35.1%) of the patch plasty group significant dilatation at the operative site was observed and reoperation for aneurysm formation was required in 15 patients (19.5%). Resection of the intimal crest did not increase the probability of aneurysm formation, whereas Dacron as patch material and late hypertension had a significant influence. Six of the ten late deaths occurred in the patch plasty group. Rupture of an aneurysm at the operative site was proved in two of these patients, and three patients died suddenly for unknown reasons. In the other groups significant dilatation was observed in 13 patients and 3 local aneurysms required reoperation (2 after end-to-end anastomosis and 1 after direct plasty). We conclude that patch plasty repair of coarctation should be abandoned in adults. End-to-end anastomosis is advisable only if possible without excessive tension. Reoperation with interposition of a tubular graft on left heart bypass proved to be a safe method.

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