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Ivan Ciric

✓ Observations under the operating microscope confirming the presence of a pituitary capsule are reported. This capsule envelops the anterior lobe of the pituitary, the neurohypophysis, and the pituitary stalk. It merges along the stalk with the intracranial pia mater. The origin and nature of this capsule are discussed in light of the known facts of development of the pituitary gland and surrounding structures. It is concluded that the pituitary gland capsule is a derivative of the primitive pia mater.

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Ivan Ciric

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Ivan Ciric and Israel Zivin

✓ The authors present two cases of neuroepithelial (colloid) cysts found above the diencephalic roof, occupying the space between the two fornices and the two leaves of the septum pellucidum, and describe the clinical history, neurological, and neuroradiological findings. Both lesions were removed through a right transventricular-transseptal approach. No other report of such a lesion in this location could be found in the review of literature. The pathogenesis of these cysts, both above and below the diencephalic roof, is discussed in light of the developmental anatomy of the area under consideration. In view of their origin from the neuroepithelium in the diencephalic roof, whether by a process of invagination into the third ventricle or by evagination into the velum interpositum, the so-called colloid cysts are more appropriately termed neuroepithelial cysts.

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Ivan S. Ciric, James L. Quinn and Paul C. Bucy

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The lateral recess syndrome

A variant of spinal stenosis

Ivan Ciric, Michael A. Mikhael, Joseph A. Tarkington and Nicholas A. Vick

✓ Sixteen patients with a surgically proven lateral recess stenosis were studied retrospectively. Lateral recess stenosis should be suspected in patients with disabling intermittent neurogenic claudications. The neurological examination is usually unremarkable. The diagnosis is assured when the lateral recess measures less than 2 mm in height. A lateral recess of 5 mm or more rules out the possibility of a lateral recess stenosis. Surgical decompression of the lateral recess requires removal of the horizontal portion of the superior articular facet.

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Ivan Ciric, Michael Mikhael, Thomas Stafford, Lawrence Lawson and Rafael Garces

✓ The authors have reported on 108 patients with pituitary macroadenomas (measuring 2 cm in at least one diameter) who underwent 117 transsphenoidal operations and five craniotomies, and were followed for periods ranging from 6 months to 14 years. Vision improved in 90% of the patients. Gross total tumor removal with no evidence of residual tumor tissue demonstrable on the postoperative computerized tomography scan was accomplished in 41% of cases. However, gross total tumor removal is not synonymous with complete tumor removal. Endocrine cure was possible in 25% of prolactin-secreting and 20% of growth hormone-secreting adenomas. The incidence of recurrence was 12%, with the majority occurring from 4 to 8 years postoperatively. Both the tumors with suprasellar extension of more than 2 cm and the hard fibrotic tumors had a higher recurrence rate. Postoperative administration of radiation therapy has been associated with a significantly lower recurrence rate than when this therapy was withheld. Transsphenoidal surgery of pituitary macroadenomas confined to the extra-arachnoid space is associated with a relatively small number of complications. The operative technique used in this series is described.

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James K. Liu, Maria Fleseriu, Johnny B. Delashaw Jr., Ivan S. Ciric, William T. Couldwell and Ph.D.

✓Cushing disease is considered an aggressive pituitary endocrinopathy because of the devastating effects from untreated hypercortisolemia. Although they are histologically benign, these adrenocorticotropic hormone (ACTH)-secreting pituitary tumors are associated with significant morbidity and premature death. Currently, transsphenoidal surgery is the primary treatment of Cushing disease associated with an ACTH-secreting pituitary tumor, resulting in remission rates ranging from about 50 to 90%. Some patients, however, will not achieve sustained remission after transsphenoidal surgery and can exhibit persistent or recurrent Cushing disease that requires multimodal treatment to achieve remission. In these patients, options for treatment include repeat transsphenoidal resection, radiation therapy (including conventional fractionated radiation therapy and stereotactic radiosurgery), and medical therapy. Despite undergoing multiple treatment modalities, some patients may ultimately require bilateral adrenalectomy for definitive treatment to eliminate hypercortisolemia associated with Cushing disease. In this article, the authors review the treatment options for patients who have persistent or recurrent Cushing disease after unsuccessful transsphenoidal surgery. The indications, current results reported in the literature, and complications of each treatment modality are discussed.

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Julian E. Bailes, Jeffrey W. Cozzens, Alan R. Hudson, David G. Kline, Ivan Ciric, Peter Gianaris, Lawrence P. Bernstein and Daniel Hunter

✓ Studies on the peripheral nerves in rats and other species have helped in the development of laser-assisted nerve anastomosis (LANA), but offer little in evaluating the efficacy of this technique in primates. The authors present a study of LANA in the peripheral nerves of rhesus monkeys. Twelve adult rhesus monkeys underwent bilateral resection of a portion of the peroneal nerve followed by placement of autogenous sural nerve interposition fascicular grafts. The grafts were completed with conventional microsurgical suture technique on one side and with LANA on the other. At 5, 8, 10, and 12 months, the grafted nerves were evaluated for continuity, nerve conduction, and histology (both light and electron microscopy). No significant difference in continuity, conduction velocity, nerve degeneration, nerve regeneration, axon fiber number, or axon fiber density was found in any animal between grafts performed by conventional microsuture and LANA grafts. There was no difference in distal or proximal myelinated fiber density between the LANA grafts and the conventional microsuture grafts. It was concluded that LANA is as effective as microsurgical suture nerve anastomosis in a primate model of nerve repair and grafting.

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Henry Brem, M. Stephen Mahaley Jr., Nicholas A. Vick, Keith L. Black, S. Clifford Schold Jr., Peter C. Burger, Allan H. Friedman, Ivan S. Ciric, Theodore W. Eller, Jeffrey W. Cozzens and James N. Kenealy

✓ Malignant gliomas have been difficult to treat with chemotherapy. The most effective agent, BCNU (carmustine), has considerable systemic toxicity and a short half-life in serum. To obviate these problems, a method has been developed for the local sustained release of chemotherapeutic agents by their incorporation into biodegradable polymers. Implantation of the drug-impregnated polymer at the tumor site allows prolonged local exposure with minimal systemic exposure. In this Phase I–II study, 21 patients with recurrent malignant glioma were treated with BCNU released interstitially by means of a polyanhydride biodegradable polymer implant. Up to eight polymer wafers were placed in the resection cavity intraoperatively, upon completion of tumor debulking. The polymer releases the therapeutic drug for approximately 3 weeks.

Three increasing concentrations of BCNU were studied; the treatment was well tolerated at all three levels. There were no adverse reactions to the BCNU wafer treatment itself The average survival period after reoperation was 65 weeks for the first dose group, 64 weeks for the second dose group, and 32 weeks for the highest dose group. The overall mean survival time was 48 weeks from reoperation and 94 weeks from the original operation. The overall median survival times were 46 weeks postimplant and 87 weeks from initial surgery. Eighteen (86%) of 21 patients lived more than 1 year from the time of their initial diagnosis and eight (38%) of 21 patients lived more than 1 year after intracranial implantation of the polymer. Frequent hematology, blood chemistry, and urinalysis tests did not reveal any systemic effect from this interstitial chemotherapy.

Since the therapy is well tolerated and safe, a placebo-controlled clinical trial has been started. The trial will measure the effect of the second treatment dose on survival of patients with recurrent malignant glioma.