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  • Author or Editor: Julian S. Rechbergerx
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Evaluating infusate parameters for direct drug delivery to the brainstem: a comparative study of convection-enhanced delivery versus osmotic pump delivery

Julian S. Rechberger, Erica A. Power, Victor M. Lu, Liang Zhang, Jann N. Sarkaria, and David J. Daniels

OBJECTIVE

Convection-enhanced delivery (CED) and osmotic pump delivery both have been promoted as promising techniques to deliver drugs to pediatric diffuse intrinsic pontine gliomas (DIPGs). Correspondingly, the aim of this study was to understand how infusate molecular weight (MW), duration of delivery, and mechanism of delivery (CED or osmotic pump) affect volume of distribution (Vd) in the brainstem, to better inform drug selection and delivery in future DIPG investigations.

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A series of in vivo experiments were conducted using rat models. CED and osmotic pump delivery systems were surgically implanted in the brainstem, and different MW fluorescent dextran beads were infused either once (acute) or daily for 5 days (chronic) in a volume infused (Vi). Brainstems were harvested after the last infusion, and Vdwas quantified using serial sectioning and fluorescence imaging.

RESULTS

Fluorescence imaging showed infusate uptake within the brainstem for both systems without complication. A significant inverse relationship was observed between infusate MW and Vdin all settings, which was distinctly exponential in nature in the setting of acute delivery across the 570-Da to 150-kDa range. Chronic duration and CED technique resulted in significantly greater Vdcompared to acute duration or osmotic pump delivery, respectively. When accounting for Vi、急性输液了significantly greater Vd/ Vithan chronic infusion. The distribution in CED versus osmotic pump delivery was significantly affected by infusate MW at higher weights.

CONCLUSIONS

Here the authors demonstrate that infusate MW, duration of infusion, and infusion mechanism all impact the Vdof an infused agent and should be considered when selecting drugs and infusion parameters for novel investigations to treat DIPGs.

InNeurosurgical Focus Volume 48 (2020): Issue 1 (Jan 2020): Pediatric Brain Tumor: Evolving Treatment Strategies

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Feasibility of probe washing after stereotactic needle biopsy as a novel technique for developing cell lines and xenografts of H3 K27–altered diffuse midline gliomas

Julian S. Rechberger, Liang Zhang, Jizhi Ge, Cody L. Nesvick, Kai J. Miller, and David J. Daniels

H3 K27–altered diffuse midline gliomas (DMGs) are frequently biopsied to obtain tissue diagnosis, inform clinical decision-making, and determine clinical trial eligibility. Tissue yield from biopsies is typically low, leaving little material available for research. To advance understanding of disease biology and promote preclinical testing of novel therapeutics, collecting viable cellular material from treatment-naive tumors is of paramount importance. Here, the authors report the feasibility of a practicable technique for creating DMG cell lines and patient-derived xenografts (PDXs) without the need for additional biopsy specimens. Tumor cells are obtained by probe washing immediately after completion of biopsy. Wash fluid is collected, and viable cells are expanded in vitro. Cultured cells are used to establish PDX rodent models. A total of 5 patient samples were collected by this technique. Viable tumor cells were obtained from 3 of the 5 samples, and cell lines suitable for experiments were obtained within 6–8 months. Orthotopic implantation and flank engraftment was successful in 1 of the 3 established cell lines. Animals harboring intracranial tumors were euthanized due to disease burden 6–7 months after stereotactic injection. Flank tumors formed within 4–5 months and were serially passaged. Molecular and tissue analyses confirmed retention of H3 K27M expression and loss of H3 K27me3 in all cell lines and PDXs.

In开云手机版app下载安装最新版神经外科杂志:儿科开云体育app官方网站下载入口Publish Before Print

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Angiographic cross-filling between inferior petrosal sinuses and alteration of adrenocorticotropic hormone sampling results for tumor localization in Cushing disease

Michael L. Martini, R. Chase Ransom, Julian S. Rechberger, Derek O’Keeffe, William Young Jr., John L. D. Atkinson, Fredric B. Meyer, Lorenzo Rinaldo, Lucas Carlstrom, Harry J. Cloft, and Jamie Van Gompel

OBJECTIVE

Inferior petrosal sinus (IPS) sampling (IPSS) is a diagnostic procedure used to guide diagnostic localization of imaging-negative adrenocorticotropic hormone (ACTH)–secreting pituitary microadenomas. However, the efficacy of IPSS has been suboptimal at accurately lateralizing the adenoma, reducing surgical cure rates and leading to unintended pituitary dysfunction due to the added exploration. One rationale for the occasional imprecision is the existence of additional petrosal sinus collateral channels that connect the IPS bilaterally, which may lead to false localization results during sampling. The aim of this study was to explore a potential connection between normal anatomical variation in the angioarchitecture of the IPSs and the ACTH results obtained in subsequent IPSS tests.

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A retrospective review was performed on all cases between 1998 and 2013 involving patients at a single institution who underwent IPSS for radiographically equivocal pituitary microadenomas. Cases were reviewed for tumor laterality noted on either operative or pathology reports, as well as the presence of angiographic evidence of cross-filling between the sinuses. In addition, ACTH levels from the right and left IPSs were documented at baseline and at 2, 5, and 10 minutes after corticotropin-releasing hormone (CRH) administration. A ratio of the change in ACTH levels measured at the time of maximal response (10 minutes) versus the levels measured at the initial response (2 minutes) was computed for each patient and compared between patients by their angiographic cross-filling status.

RESULTS

There were 41 patients with a histopathologically confirmed right- or left-sided ACTH-secreting pituitary microadenoma who underwent preoperative IPSS. Among these patients, 28 (68%) showed angiographic evidence of cross-filling between the IPSs, and 13 showed no cross-filling. On average, ACTH levels increased by a factor of 3.91 ± 0.77 in the contralateral IPS in patients with angiographic cross-filling, compared with a factor increase of only 1.80 ± 0.27 in patients without cross-filling (p = 0.014). In comparison, ACTH levels increased by a factor of 2.01 ± 0.57 in the ipsilateral IPS in patients with cross-filling, and by 8.78 ± 7.30 in those without cross-filling (p = 0.373).

CONCLUSIONS

The presence of angiographic cross-filling, suggestive of a greater degree of vascular channel networking between the right and left IPS, is a significant factor influencing the measured rates of change of ACTH in IPSS and may impact the specificity of this test to accurately determine microadenoma laterality in the preoperative setting.

InJournal of Neurosurgery Publish Before Print

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