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Wesley Hsu, Khan W. Li, Markus Bookland and George I. Jallo

In the early 1920s, Walter E. Dandy began translating the field of endoscopy to neurosurgery. In the ensuing years, Dandy, who would become known as the “Father of Neuroendoscopy,” applied his own ingenuity in combination with guidance from prominent medical contemporaries in the development of the early neuroendoscope. This paper reviews his contributions to the early evolution of this growing and important field of neurosurgery.

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Khan W. Li, Clarke Nelson, Ian Suk and George I. Jallo

Neuroendoscopy began with a desire to visualize the ventricles and deeper structures of the brain. Unfortunately, the technology available to early neuroendoscopists was not sufficient in most cases for these purposes. The unique perspective that neuroendoscopy offered was not fully realized until key technological advances made reliable and accurate visualization of the brain and ventricles possible. After this technology was incorporated into the device, neuro-endoscopic procedures were rediscovered by neurosurgeons. Endoscopic third ventriculostomy and other related procedures are now commonly used to treat a wide array of neurosurgically managed conditions. A seemingly limitless number of neurosurgical applications await the endoscope. In the future, endoscopy is expected to become routine in modern neurosurgical practice and training.

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Francesco Dimeco, Richard E. Clatterbuck, Khan W. Li, Edward F. McCarthy and Alessandro Olivi

✓ The synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a recently described, currently evolving clinical entity that groups together several idiopathic disorders of bone and skin formerly described under a variety of names. Among the spectrum of possible locations for the bone lesions, there is no previous report in the literature of primary involvement of the skull vault. A patient with primary involvement of the calvaria in the setting of SAPHO syndrome is described here, which, to the authors' knowledge, is the first report of such localization. The clinically and radiologically benign evolution of the different stages of the bone lesions is presented. The authors suggest that the SAPHO syndrome should be considered in the differential diagnosis of lytic, sclerotic, or hyperostotic lesions of the skull, particularly before considering invasive diagnostic procedures.

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Francesco DiMeco, Khan W. Li, Betty M. Tyler, Ariel S. Wolf, Henry Brem and Alessandro Olivi

Object. Mitoxantrone is a drug with potent in vitro activity against malignant brain tumor cell lines; however, its effectiveness as a systemic agent has been hampered by poor central nervous system penetration and dose-limiting myelosuppression. To avoid these problems, we incorporated mitoxantrone into biodegradable polymeric wafers to be used for intracranial implantation, a strategy that has been shown to be safe and successful in the treatment of malignant gliomas. The authors investigated the release kinetics, toxicity, distribution, and efficacy of mitoxantrone delivered from intracranially implanted biodegradable wafers in the treatment of 9L gliosarcoma in Fischer 344 rats.

Methods. Mitoxantrone released from the biodegradable wafer matrix reached therapeutic drug concentrations in the brain for at least 35 days. Only animals with implanted wafers of the highest drug loading dose (20% mitoxantrone by weight) showed signs of significant toxicity. In three separate efficacy experiments, animals treated with mitoxantrone-loaded biodegradable wafers had significantly improved survival compared with control animals. The combined median survival for each treatment group was the following: 0% mitoxantrone wafers, 19 days; 1%, 30 days, p < 0.0001; 5%, 34 days, p < 0.0001; and 10%, 50 days, p < 0.0001.

Conclusions. These findings establish that mitoxantrone delivered from intracranially implanted biodegradable wafers is effective in the treatment of malignant gliomas in rodents and should be considered for future clinical application in humans.

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Khan W. Li, Chanland Roonprapunt, Herman C. Lawson, I. Rick Abbott, Jeffrey Wisoff, Fred Epstein and George I. Jallo

Object

Tectal gliomas are a distinct form of pediatric brainstem tumor that present in patients with symptoms related to increased intracranial pressure due to obstructive hydrocephalus. The natural history of these lesions is often uniquely indolent. Thus, initial surgical therapies are directed at treatment of hydrocephalus, usually with ventricular shunt placement. Recently, third ventriculostomy has been used in patients with tectal gliomas, both as an initial procedure and after shunt failures. In this report the authors review their experience with the treatment of hydrocephalus in patients with tectal gliomas.

Methods

The authors reviewed 31 consecutive cases of tectal gliomas and compared the success rates of ventricular shunt placement with the success rates of endoscopic third ventriculostomy (ETV). Shunt placement procedures were associated with a significant number of malfunctions, and most patients required shunt revisions. The ETV procedure was attempted both as an initial treatment and after shunt malfunction. Overall, ETV was attempted in 18 patients and was performed successfully in all cases. At the time of follow-up evaluation, 16 patients (89%) were shunt free.

Conclusions

The authors found that ETV could be performed with good long-term success both as an initial treatment and after shunt failure. Overall, ETV was found to be superior to ventricular shunt placement in the management of hydrocephalus associated with tectal gliomas.

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Patrik Gabikian, Betty M. Tyler, Irma Zhang, Khan W. Li, Henry Brem and Kevin A. Walter

Object

The aim of this study was to demonstrate that paclitaxel could function as a radiosensitizer for malignant glioma in vitro and in vivo.

Methods

The radiosensitizing effect of paclitaxel was tested in vitro using the human U373MG and rat 9L glioma cell lines. Cell cycle arrest in response to paclitaxel exposure was quantified by flow cytometry. Cells were subsequently irradiated, and toxicity was measured using the clonogenic assay. In vivo studies were performed in Fischer 344 rats implanted with intracranial 9L gliosarcoma. Rats were treated with control polymer implants, paclitaxel controlled-release polymers, radiotherapy, or a combination of the 2 treatments. The study end point was survival.

Results

Flow cytometry demonstrated G2-M arrest in both U373MG and 9L cells following 6–12 hours of paclitaxel exposure. The order in which the combination treatment was administered was significant. Exposure to radiation treatment (XRT) during the 6–12 hours after paclitaxel treatment resulted in a synergistic reduction in colony formation. This effect was greater than the effect from either treatment alone and was also greater than the effect of radiation exposure followed by paclitaxel. Rats bearing 9L gliosarcoma tumors treated with paclitaxel polymer administration followed by single-fraction radiotherapy demonstrated a synergistic improvement in survival compared with any other treatment, including radiotherapy followed by paclitaxel treatment. Median survival for control animals was 13 days; for those treated with paclitaxel alone, 21 days; for those treated with XRT alone, 21 days; for those treated with XRT followed by paclitaxel, 45 days; and for those treated with paclitaxel followed by XRT, more than 150 days (p < 0.0001).

Conclusions

These results indicate that paclitaxel is an effective radiosensitizer for malignant gliomas because it renders glioma cells more sensitive to ionizing radiation by causing G2-M arrest, and induces a synergistic response to chemoradiotherapy.

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Patrick C. Hsieh, Tyler R. Koski, Daniel M. Sciubba, Dave J. Moller, Brian A. O'shaughnessy, Khan W. Li, Ziya L. Gokaslan, Stephen L. Ondra, Richard G. Fessler, and John C. Liu

Minimally invasive surgery (MIS) in the spine was primarily developed to reduce approach-related morbidity and to improve clinical outcomes compared with those following conventional open spine surgery. Over the past several years, minimally invasive spinal procedures have gained recognition and their utilization has increased. In particular, MIS is now routinely used in the treatment of degenerative spine disorders and has been shown to be as effective as conventional open spine surgeries. Although the procedures are not yet widely recognized in the context of complex spine surgery, the true potential in minimizing approach-related morbidity is far greater in the treatment of complex spinal diseases such as spinal trauma, spinal deformities, and spinal oncology. Conventional open spine surgeries for complex spinal disorders are often associated with significant soft tissue disruption, blood loss, prolonged recovery time, and postsurgical pain. In this article the authors review numerous cases of complex spine disorders managed with MIS techniques and discuss the current and future implications of these approaches for complex spinal pathologies.

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Betty Tyler, Kirk D. Fowers, Khan W. Li, Violette Renard Recinos, Justin M. Caplan, Alia Hdeib, Rachel Grossman, Luca Basaldella, Kimon Bekelis, Gustavo Pradilla, Federico Legnani and Henry Brem

Object

Paclitaxel, a cellular proliferation inhibitor/radiation sensitizer, while effective against gliomas in vitro, has poor CNS penetration and dose-limiting toxicities when administered systemically. OncoGel (paclitaxel in Re-Gel) provides controlled local paclitaxel release when placed into the CNS. The authors evaluated the safety and efficacy of OncoGel in rats with intracranial 9L gliosarcoma.

Methods

Safety studies included intracranial delivery of increasing volumes of ReGel and OncoGel containing 1.5 (OncoGel 1.5) or 6.3 (OncoGel 6.3) mg/ml paclitaxel. An in vivo radiolabeled biodistribution study was performed in 18 Fischer-344 rats to determine intracerebral distribution. Efficacy studies compared overall survival for controls, ReGel only, radiation therapy only, OncoGel 6.3, or OncoGel 6.3 in combination with radiation therapy. ReGel and OncoGel 6.3 were delivered either simultaneously with tumor implantation (Day 0) or 5 days later (Day 5). Radiation therapy was given on Day 5.

Results

Control and ReGel animals died of tumor within 17 days. Survival significantly increased in the Onco-Gel 6.3 group on Day 0 (median 31 days; p = 0.0001), in the OncoGel 6.3 group on Day 5 (median 17 days; p = 0.02), and in the radiation therapy–only group (median 26 days; p = 0.0001) compared with controls. Animals receiving both OncoGel and radiation therapy had the longest median survival: 83 days in the group with radiation therapy combined with OncoGel 6.3 on Day 0, and 32 days in the group combined with OncoGel 6.3 on Day 5 (p = 0.0001 vs controls). After 120 days, 37.5% of the animals in the OncoGel Day 0 group, 37.5% of animals in the OncoGel 6.3 Day 0 in combination with radiation therapy group, and 12.5% of the animals in the OncoGel 6.3 on Day 5 in combination with radiation therapy group were alive. In the biodistribution study, measurable radioactivity was observed throughout the ipsilateral hemisphere up to 3 weeks after the OncoGel injection, with the most radioactivity detected 3 hours after injection. The highest dose of radioactivity observed in the contralateral hemisphere was at the Day 3 time point.

Conclusions

OncoGel containing 6.3 mg/ml of paclitaxel is safe for intracranial injection in rats and effective when administered on Day 0. When combined with radiation therapy, the combination was more effective than either therapy alone and should be studied clinically for the treatment of malignant glioma.