Neuro-oncology
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Extent of resection (EOR) still remains controversial in therapy of glioblastoma multiforme (GBM). However, an increasing number of studies favor maximum EOR as being associated with longer patient survival. One hundred thirty-five GBM patients underwent tumor resection aided by 1.5T intraoperative MRI (iMRI) and integrated multimodal navigation. ⋯ To our knowledge, this is the largest study including correlation of iMRI, tumor volumetry, and survival time. We demonstrate that navigation guidance and iMRI significantly contribute to optimal EOR with low postoperative morbidity, where EOR ≥ 98% and patient age <65 years are associated with significant survival advantages. Thus, maximum EOR should be the surgical goal in GBM surgery while preserving neurological function.
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Acoustic neuromas present a challenging problem, with the major treatment modalities involving operative excision, stereotactic radiosurgery, observation, and fractionated stereotactic radiotherapy. The morbidity/mortality following excision may differ by patient race. To address this concern, the morbidity of acoustic neuroma excision was assessed on a nationwide level. ⋯ Neither hospital caseload nor median income were predictive factors. African Americans were 9 times more likely to die following surgery than Caucasians over a decade-long analysis. Given the relatively benign natural history of acoustic neuroma and the alarmingly increased mortality rate following surgical excision among older patients, African Americans, and patients receiving care from low-caseload surgeons, acoustic neuromas in these patient populations may be best managed by a more minimally invasive modality such as observation, fractionated stereotactic radiotherapy, or stereotactic radiosurgery.
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Patients with von Hippel-Lindau (VHL) syndrome with diffuse CNS hemangioblastomas have morbidity related to their disease and require a lifetime of surgical resections. Ninety-seven percent of tumors progress, and 5-year surgery rates are 20%-60%. Stereotactic radiosurgery and fractionated radiotherapy have had limited success. ⋯ Clinical and radiographic stability or resolution was demonstrated in the majority of tumors. Tumor growth rate in this study was less than reported in natural history studies, and the rate of surgical intervention was reduced. ICSRT was well tolerated, can decrease hemangioblastoma growth rate, and is a potential therapeutic option for VHL patients that warrants further investigation.
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Extent of resection is a major goal and prognostic factor in the treatment of gliomas. In this study we evaluate whether quantitative ex vivo tissue measurements of δ-aminolevulinic acid-induced protoporphyrin IX (PpIX) identify regions of increasing malignancy in low- and high-grade gliomas beyond the capabilities of current fluorescence imaging in patients undergoing fluorescence-guided resection (FGR). Surgical specimens were collected from 133 biopsies in 23 patients and processed for ex vivo neuropathological analysis: PpIX fluorimetry to measure PpIX concentrations (C(PpIX)) and Ki-67 immunohistochemistry to assess tissue proliferation. ⋯ Furthermore, a large percentage of tumor-positive biopsy sites (∼40%) that were not visibly fluorescent under the operating microscope had levels of C(PpIX) greater than 0.1 µg/mL, which indicates that significant PpIX accumulation exists below the detection threshold of current fluorescence imaging. Although PpIX fluorescence is recognized as a visual biomarker for neurosurgical resection guidance, these data show that it is quantitatively related at the microscopic level to increasing malignancy in both low- and high-grade gliomas. This work suggests a need for improved PpIX fluorescence detection technologies to achieve better sensitivity and quantification of PpIX in tissue during surgery.
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Intracerebral convection-enhanced delivery (CED) of chemotherapeutic agents currently requires an externalized catheter and infusion system, which limits its duration because of the need for hospitalization and the risk of infection. To evaluate the feasibility of prolonged topotecan administration by CED in a large animal brain with the use of a subcutaneous implantable pump. Medtronic Synchromed-II pumps were implanted subcutaneously for intracerebral CED in pigs. ⋯ Intracerebral topotecan CED is well tolerated in a large animal brain for up to 10 days. Intracerebral long-term CED can be achieved with a subcutaneously implanted pump and provides a stable volume of distribution. This work constitutes a proof of principle for the safety and feasibility for prolonged CED, providing a means of continuous local drug delivery that is accessible to the practicing neuro-oncologist.