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Uwe M. H. Schrell, Michael G. Rittig, Marc Anders, Uwe H. Koch, Rolf Marschalek, Franklin Kiesewetter and Rudolf Fahlbusch

✓ In this paper the authors present the first evidence that meningiomas respond to treatment with hydroxyurea. Hydroxyurea was administered as an adjunct chemotherapeutic treatment in patients with recurrent and unresectable meningiomas. Hydroxyurea was used because experimental data demonstrated that it inhibits growth of cultured human meningioma cells and meningioma transplants in nude mice by inducing apoptosis. The authors therefore treated four selected patients with hydroxyurea. All patients had undergone multiple gross resections and all except one received radio-therapy. Three patients with recurrent Grade I meningiomas assessed according to World Health Organization (WHO) guidelines received hydroxyurea because of an increased tumor growth rate, documented by magnetic resonance (MR) imaging, within a 6- or 12-month interval. A fourth patient with a malignant meningioma (WHO Grade III) began a course of treatment with hydroxyurea immediately after his sixth palliative operation without waiting for another relapse to be demonstrated on MR imaging. Because of their location and invasive growth behavior none of the meningiomas could have been removed completely by surgical intervention.

All patients received hydroxyurea at a dosage level of 1000 to 1500 mg/day (approximately 20 mg/kg/day). In a man with a large sphenoid wing meningioma invading the right cavernous sinus and the temporal base, the intracranial tumor mass was reduced by 60% during 6 months of treatment. A woman with a large ball-shaped meningioma of the right sphenoid wing invading the cavernous sinus exhibited a 74% decrease of the initial tumor volume in 10 months of treatment with oral hydroxyurea. Serial MR images obtained monthly revealed that the process of size reduction was continuous and proportionate. The shrinkage of the tumor was accompanied by a complete remission of symptomatic trigeminal neuralgia after 2 months and by improved abducent paresis after 5 months. The third patient had a slowly growing meningioma that exhibited a 15% reduction in mass when reassessed after 5 months of hydroxyurea treatment. The fourth patient with the malignant meningioma in the left cerebellopontine angle has had no recurrence for 24 months. Long-term treatment with hydroxyurea may result in full remission of tumors in meningioma patients.

The preliminary data indicate that hydroxyurea provides true medical treatment in patients with unresectable and recurrent meningiomas, replacing palliative surgery and radiotherapy in the management of this disease.

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Uwe M. H. Schrell, Michael G. Rittig, Marc Anders, Uwe H. Koch, Rolf Marschalek, Franklin Kiesewetter and Rudolf Fahlbusch

In this paper the authors present the first evidence that meningiomas respond to treatment with hydroxyurea. Hydroxyurea was administered as an adjunct chemotherapeutic treatment in patients with recurrent and unresectable meningiomas. Hydroxyurea was used because experimental data demonstrated that it inhibits growth of cultured human meningioma cells and meningioma transplants in nude mice by inducing apoptosis. The authors therefore treated four selected patients with hydroxyurea. All patients had undergone multiple gross resections and all except one received radiotherapy. Three patients with recurrent Grade I meningiomas assessed according to World Health Organization (WHO) guidelines received hydroxyurea because of an increased tumor growth rate, documented by magnetic resonance (MR) imaging, within a 6- or 12-month interval. A fourth patient with a malignant meningioma (WHO Grade III) began a course of treatment with hydroxyurea immediately after his sixth palliative operation without waiting for another relapse to be demonstrated on MR imaging. Because of their location and invasive growth behavior none of the meningiomas could have been removed completely by surgical intervention.

All patients received hydroxyurea at a dosage level of 1000 to 1500 mg/day (approximately 20 mg/kg/day). In a man with a large sphenoid wing meningioma invading the right cavernous sinus and the temporal base, the intracranial tumor mass was reduced by 60% during 6 months of treatment. A woman with a large ball-shaped meningioma of the right sphenoid wing invading the cavernous sinus exhibited a 74% decrease of the initial tumor volume in 10 months of treatment with oral hydroxyurea. Serial MR images obtained monthly revealed that the process of size reduction was continuous and proportionate. The shrinkage of the tumor was accompanied by a complete remission of symptomatic trigeminal neuralgia after 2 months and by improved abducent paresis after 5 months. The third patient had a slowly growing meningioma that exhibited a 15% reduction in mass when reassessed after 5 months of hydroxyurea treatment. The fourth patient with the malignant meningioma in the left cerebellopontine angle has had no recurrence for 24 months. Long-term treatment with hydroxyurea may result in full remission of tumors in meningioma patients.

The preliminary data indicate that hydroxyurea provides true medical treatment in patients with unresectable and recurrent meningiomas, replacing palliative surgery and radiotherapy in the management of this disease.

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Toru Hayakawa, Kazuyoshi Morimoto, Yukitaka Ushio, Takesada Mori, Toshiki Yoshimine, Akio Myoga and Heitaro Mogami

0 carbon monoxide poisoning 3 0 0 0 control 8 0 0 0 TABLE 4 Summary of preoperative astroprotein levels in the cerebrospinal fluid of 128 patients * Category Total Cases > 25 ng/ml > 100 ng/ml > 500 ng/ml No. % No. % No. % A: gliomas 30 13 43.3 7 23.3 4 13.3 B: nonglial brain tumors 57 9 15.8 1  1.8 0  0 C: non-neoplastic intracranial diseases 33 7 21.2 3  9.1 0  0 D: control 8 0

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Jaclyn J. Renfrow, Garret P. Greeneway, Lacey Carter and Daniel E. Couture

C raniopharyngiomas are benign tumors that arise from the squamous epithelial cells of Rathke’s pouch, an embryological structure that extends midline connecting the sella to the hypothalamus and floor of the third ventricle. 5 Craniopharyngiomas are the most prevalent nonglial brain tumors in children and account for approximately 5% of pediatric brain tumors. 12 They are typically treated using resection, although it is often challenging due to their invasive tendencies and proximity to the optic chiasm and pituitary stalk. 4 Despite treatment with

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Robert E. Elliott, Yaron A. Moshel and Jeffrey H. Wisoff

C raniopharyngiomas are the most common nonglial brain tumors of childhood, comprising 6–8% of pediatric brain tumors. 5 , 9 , 36 These lesions arise from embryological squamous epithelial remnants of the craniopharyngeal duct, or Rathke pouch, which extends along an axis from the sella turcica, pituitary gland, and pituitary stalk to the hypothalamus and floor of the third ventricle. 39 , 45 , 46 , 58 , 60 Despite their benign histopathological characteristics, their clinical course is often rather malignant, and recurrence of craniopharyngiomas is one

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Keisuke Tsutsumi, Naoki Kitagawa, Masami Niwa, Akihiko Himeno, Kohtaro Taniyama and Shobu Shibata

autocrine or paracrine growth mechanisms of certain brain tumors, including meningioma, 12, 28, 31 a nonglial brain tumor originating from mesenchymal tissues in the central nervous system. Insulin-like growth factor (IGF)-I is a candidate for such an autocrine regulator in human meningioma cells. 9, 12 We investigated the effect of suramin on IGF-I binding to surgically excised human meningioma tissue and on proliferation of cultured meningioma cells in vitro . Materials and Methods Tumor Specimens and Materials Fresh surgically excised human meningioma

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Robert E. Elliott, Yaron A. Moshel and Jeffrey H. Wisoff

C raniopharyngiomas are the most common nonglial brain tumor in children, comprising 6–8% of pediatric brain tumors. 6 , 10 , 40 These lesions are benign epithelial neoplasms that most commonly grow into the sella and suprasellar cistern and have intimate relationships with the circle of Willis, third ventricle, hypothalamus, optic pathways, and pituitary stalk. They are thought to arise from embryological squamous epithelial remnants of the craniopharyngeal duct or Rathke's pouch. 45 , 50 , 52 , 75 , 78 Imaging findings of craniopharyngiomas in

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Robert E. Elliott and Jeffrey H. Wisoff

C raniopharyngiomas are the most common nonglial brain tumors of childhood, constituting 6–8% of pediatric brain tumors. 2 , 6 , 38 They are benign neoplasms thought to arise from embryological remnants of squamous epithelium of the craniopharyngeal duct. 46 , 54 They most commonly arise in the suprasellar region and have intimate relationships with the hypothalamus, optic pathways, pituitary stalk, and, importantly, the circle of Willis. In addition to the chronic and severe debilitation caused by hypothalamic injury, the risks of ICA injury during

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Matthias Millesi, Barbara Kiesel, Adelheid Woehrer, Johannes A. Hainfellner, Klaus Novak, Mauricio Martínez-Moreno, Stefan Wolfsberger, Engelbert Knosp and Georg Widhalm

on this technique—that is, increasing the extent of resections in malignant gliomas—5-ALA was also used for visualizing nonglial brain tumors such as meningiomas and metastases. 2 , 4 , 14 , 15 , 44 Recently, 5-ALA was applied for the intraoperative visualization of spinal tumors in single cases and two small studies. 5 , 7 , 12 , 23 , 28 , 33 Protoporphyrin IX fluorescence was observed particularly in ependymomas, meningiomas, and malignant gliomas. Note, however, that a systematic analysis of the value of 5-ALA for intraoperative visualization of different

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Uwe M. H. Schrell, Michael G. Rittig, Marc Anders, Franklin Kiesewetter, Rolf Marschalek, Uwe H. Koch and Rudolf Fahlbusch

met with minor success. 39, 40, 51 However, meningiomas are nonglial brain tumors that have nothing in common with glial brain tumors such as astrocytomas and glioblastomas. Hydroxyurea has never been used to treat cerebral meningiomas in vitro or in vivo. At present, hydroxyurea is used in solid tumors as an accompanying therapy prior to radiation therapy or chemotherapy for the purpose of tumor cell synchronization. With respect to hematopoietic disorders, hydroxyurea is the treatment of choice for patients with chronic myelogenous leukemia. 29 Based on these