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Object Embryonic stem (ES) cell–derived astrocytes have several theoretical and practical advantages as gene therapy vectors in the treatment of malignant gliomas. The aim of this study was to test the proapoptotic effects of ES cell–derived astrocytes expressing transgenic tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) in human malignant glioma cells. Methods Mouse ES cells containing a doxycycline-inducible transgene were engineered with human TRAIL (hTRAIL) and then directed to differentiate into astrocytes. The ES cell-derived–TRAIL-expressing astrocytes were cocultured with human malignant glioma cells. Reverse transcriptase polymerase chain reaction, immunocytochemistry, terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling, and flow cytometry were used to quantify results. In vitro coculture of ES cell–derived astrocytes expressing hTRAIL with A172 human malignant glioma cells after doxycycline induction caused a significant decrease in cell viability from 85 ± 2% at baseline to 8 ± 2% posttreatment (p < 0.001). Labeling with apoptotic markers showed that cell death occurred by means of apoptosis. A significant increase in apoptotic rate (88 ± 3%) from baseline (4 ± 2%) was found in A172 cells after doxycycline induction (p < 0.005). This effect was superior to the apoptotic rate seen after treatment with recombinant TRAIL (57 ± 2%). A decrease in cell viability and an increase in the apoptotic rate were not found in TRAIL-expressing–ES cell-derived astrocytes after induction with doxycycline or in A172 cells exposed to doxycycline alone. Conclusions Engineering of transgenic hTRAIL by using ES cell–derived astrocytes induced apoptosis in human malignant glioma cells while sparing nontumor astrocytes. The apoptotic effects of transgenic hTRAIL are greater than those of recombinant hTRAIL. Analysis of these results suggests that hTRAIL-expressing–ES cell-derived astrocytes should be considered in the development of new in vivo strategies to treat malignant human gliomas.

Object. In this paper the authors describe the indications for and the results and complications of repeated transsphenoidal surgery (RTSS) to treat recurrent or residual pituitary adenoma. Methods. A retrospective review was conducted of 96 consecutive patients who underwent RTSS to treat recurrent or residual pituitary adenoma. Ninety-six patients underwent RTSS: 42 to treat a recurrent or residual pituitary mass and 54 to treat a recurrent or persistent hormone hypersecretion. There was no case of perioperative death and there was a 1% incidence of major complications. Postoperative endocrinological deficiencies were uncommon unless planned total hypophysectomy was performed to treat Cushing disease. Clinical remission occurred in 93% of patients undergoing RTSS to treat a tumor mass, and 15% of patients initially experienced remission only to face a relapse after a mean of 32 months. Endocrinological remission occurred in 57% of patients undergoing RTSS to treat hormone hypersecretion; most of these patients had Cushing disease. Thirty-five percent of patients with an initial endocrinological remission experienced a relapse of their symptoms after a mean of 31 months (thus, 37% of patients achieved sustained endocrinological remission). We failed to identify factors that accurately predicted initial symptom remission or delayed relapse following RTSS. Ten patients in our series eventually underwent a third transsphenoidal surgery without major complications. Conclusions. Repeated transsphenoidal surgery is a more effective treatment for recurrent or residual mass than it is for hormone hypersecretion and has acceptable rates of morbidity and mortality. If hypophysectomy is not performed, endocrinological deficiencies are unlikely following RTSS.

Object. The aim of this study was to identify the optimal surgical goals and techniques for managing symptomatic Rathke cleft cysts (RCCs). Methods. The authors conducted a retrospective study of 62 consecutive patients who had undergone surgery for RCCs. Postoperative follow up was a mean of 28 months. Fifty-six patients underwent transsphenoidal cyst decompression and biopsy procedures, and six underwent cyst wall resection. Postoperatively, symptoms improved in 91% of patients with headaches and 92% of patients with visual deficits. Decompression and biopsy were associated with a 10% incidence of new anterior pituitary hormone deficiencies and a 6% incidence of new permanent diabetes insipidus; the incidence of new hormone deficiencies was significantly higher in the few patients who had undergone cyst wall resection. The incidence of relapse, defined as cyst regrowth with either recurrent symptoms or chiasmal compression, was 16%. Resection of the cyst wall was associated with a trend toward a decreased risk of relapse. Sellar packing, sellar floor reconstruction, and irrigation with absolute ethanol did not affect the likelihood of relapse. Squamous metaplasia and inflammation increased the risk of relapse. Residual cyst demonstrated on postoperative magnetic resonance imaging was associated with an increased risk of subsequent asymptomatic cyst regrowth. Seven patients (11%) underwent repeated operation with symptomatic improvement and minimal morbidity; only one patient relapsed following a second surgery. Conclusions. Decompression and biopsy procedures in the treatment of RCCs lead to improvement in signs and symptoms, with low morbidity rates. Repeated operations will be required in as many as 16% of patients but are also associated with symptomatic improvement, low morbidity, and durable remission. Decompression and biopsy may represent the optimal surgical management of RCC.

Object Frameless image-guided stereotaxy is often used in the resection of high-grade gliomas. The authors of several studies, however, have suggested that brain shift may occur intraoperatively and result in inaccurate resection. To determine the usefulness of frameless stereotactic image-guided surgery of high-grade gliomas, the authors correlated factors predictive of brain shift, such as tumor size, periventricular location, and patient age (as an indicator of brain atrophy) with the extent of resection. Methods Inclusion criteria included the following: 1) stereotactic volumetric craniotomy for resection of tumor; 2) histologically proven high-grade glioma; 3) preoperative magnetic resonance (MR) imaging demonstration of an enhancing portion of tumor; 4) postoperative MR imaging within 48 hours to assess the extent of resection; and 5) preoperative intention to perform gross-total resection of the enhancing tumor. Fifty-four patients met these criteria between September 1997 and November 2002. Accurate resection was considered to be indicated by a lack of nodular enhancement on postoperative Gd-enhanced MR images obtained within 48 hours of surgery. Frameless stereotactic image-guided surgery resulted in the successful resection of 46 (85%) of 54 high-grade gliomas. Accurate resection was significantly more likely with tumors less than 30 ml in volume than with those greater than 30 ml (93 and 58%, respectively [p < 0.05]). In addition, small periventricular tumors were associated with significant less successful resection compared with nonperiventricular tumor (77 and 96%, respectively [p = 0.5]). Patient age did not affect the likelihood of successful resection. Conclusions Frameless image-guided stereotactic techniques can be reliably used for accurate resection of high-grade gliomas when the tumor is less than 30 ml in volume and not adjacent to the ventricular system. In cases involving tumors larger in volume or located near the ventricles, intraoperative ultrasonography or MR imaging updates should be considered.