Endoscope-assisted infratentorial-supracerebellar approach to the third ventricle : an anatomical study

Object. The authors studied the microsurgical anatomy and endoscopic features of the pineal region and third ventricle to describe a combined microsurgical-endoscopic infratentorial-supracerebellar approach to the posterior third ventricle. Such an approach exposes the pineal gland and its complex neurovascular structures so that the third ventricle can be reached through a minimally invasive parapineal incision. Methods. The approach was studied in 10 adult cadaveric heads, six fresh and four formalin fixed, by using an operative microscope with a magnification level of 6 to 40 and the assistance of an endoscope. The endoscope-assisted infratentorial- supracerebellar approach affords a complete view of the third ventricle from a posterior perspective. The third ventricle is entered through a parapineal incision using the natural space between the internal cerebral vein and the vein of Rosenthal located above the superior colliculi. Conclusions. The infratentorial-supracerebellar approach to the third ventricle follows a natural corridor and requires minimal retraction and resection of critical neural structures. With the use of the endoscope, an unsurpassed view into the third ventricle from a posterior perspective is obtained

Lactacystin exhibits potent anti-tumor activity in an animal model of malignant glioma when administered via controlled-release polymers

Lactacystin, a proteasome-inhibitor, has been shown to induce apoptosis of experimental gliomas in vitro. However, its systemic toxicity prevents further clinical use. To circumvent this problem, lactacystin can be delivered intratumorally. We tested the efficacy of lactacystin incorporated into controlled-release polymers for treating experimental gliomas. 9L-gliosarcoma and F98-glioma cell lines were treated with lactacystin (10-100 mu g/ml) for 72 h in vitro. Cell-viability was measured with MTT-assays. Toxicity of lactacystin/polycarboxyphenoxypropane-sebacic-acid (pCPP : SA) polymers was tested in vivo using Fischer-344 rats intracranially implanted with lactacystin polymers loaded from 0.1 to 2% lactacystin by weight. The efficacy of 1, 1.3, 1.5 and 1.7% lactacystin/pCPP : SA polymers was determined in Fischer-344 rats intracranially challenged with 9L and treated either simultaneously or 5 days after tumor implantation. Lactacystin was cytotoxic in 9L cells, causing a 16 +/- 8% growth inhibition at 10-mu g/ml that increased to 78 +/- 4% at 100-mu g/ml. Similarly, lactacystin inhibited growth of F98 by 18 +/- 8% at 10-mu g/ml and 74 +/- 2% at 100-mu g/ml in vitro. Polymers released lactacystin for 21 days and intracranial implantation in rats neither generate local nor systemic toxicity at doses lower than 2%. Treatment with lactacystin/pCPP : SA polymers with loading concentrations of 1.0, 1.3, and 1.5% prolonged survival of animals intracranially challenged with 9L when polymers where inserted in the day of tumor implantation. In conclusion, lactacystin exhibits potent cytotoxic-activity against 9L and F98 in vitro, it can be efficiently incorporated and delivered using controlled-release polymers, and at the proposed concentrations lactacystin polymers are safe for CNS delivery and prolong survival in the 9L model