OBJECTIVEIn this clinical trial report, the authors analyze safety and infusion distribution of IL13-Pseudomonas exotoxin, an antitumor chimeric molecule, administered via intratumoral convection enhanced delivery (CED) in pediatric patients with diffuse intrinsic pontine glioma (DIPG).METHODSThis was a Phase I single-institution, open-label, dose-escalation, safety and tolerability study of IL13-PE38QQR infused via single-catheter CED into 5 pediatric DIPG patients. IL13-PE38QQR was administered to regions of tumor selected by radiographic findings. Two escalating dose levels were evaluated: 0.125 µg/mL in cohort 1 and 0.25 µg/mL in cohort 2. Real-time MRI was performed during intratumoral infusions, and MRI and MR spectroscopy were performed before and after the infusions. Clinical evaluations, including parent-reported quality of life (QOL), were assessed at baseline and 4 weeks post-infusion.RESULTSDirect infusion of brainstem tumor with IL13-PE using the CED technique in patients with DIPG produced temporary arrest of disease progression in 2 of 5 patients, both of whom subsequently received a second infusion. All 5 patients showed signs of disease progression by 12 weeks after initial infusion. Two patients experienced transient cranial nerve deficits and lethargy after infusion, and these deficits resolved with corticosteroid treatment in both cases. No patient had radiographic evidence of acute or long-term treatment toxicity. Parent-reported QOL was consistent with medical outcomes.CONCLUSIONSEven though IL13-PE delivered by CED did not reach the entire MRI-defined tumor volume in any patient, short-term radiographic antitumor effects were observed in 2 of the 5 patients treated. The patients’ performance status did not improve. Drug delivery using multiple catheters may produce improved outcomes.Clinical trial registration no.: NCT00088061 (clinicaltrials.gov)

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OBJECTIVE Cerebral extracranial-intracranial (EC-IC) direct bypass is a commonly used procedure for ischemic vasculopathy. A previously described variation of this technique is to utilize one donor artery to supply two recipient arteries, which the authors designate as 1D2R. The purpose of this study is to present a single surgeon’s series of 1D2R direct bypasses for moyamoya and ischemia using detailed clinical, angiographic, and intraoperative blood flow measurement data. To the authors’ knowledge, this is the largest series reported to date. METHODS Hospital, office, and radiographic imaging records for all patients who underwent cerebral revascularization using a 1D2R bypass by the senior author were reviewed. The patients’ demographic information, clinical presentation, associated medical conditions, intraoperative information, and postoperative course were obtained from reviewing the medical records. RESULTS A total of 21 1D2R bypasses were performed in 19 patients during the study period. Immediate bypass patency was 100% and was 90% on delayed follow-up. The mean initial cut flow index (CFI(i)) was 0.64 ± 0.33 prior to the second anastomosis and the mean final value (CFI(f)) was 0.94 ± 0.38 after the second anastomosis (p < 0.001). The overall bypass flow increased on average by 50% (mean 17.9 ml/min, range −10 to 40 ml/min) with the addition of the second anastomosis. There was no significant difference in the overall flow measurements when the end-to-side anastomosis or side-to-side anastomosis was performed first. There was a statistically significant difference in the proportion of patients with a modified Rankin Scale (mRS) score of 0 or 1 postoperatively compared to preoperatively (p < 0.01). Through the application of Poiseuille’s law, the authors analyzed flow dynamics, deduced the component vascular resistances based on an analogy to electrical circuits and Ohm’s law, and introduced the new concepts of “second anastomosis relative augmentation” and “second anastomosis sink index” in the evaluation of 1D2R bypasses. CONCLUSIONS The application of the 1D2R technique in a series of 19 consecutive patients undergoing direct EC-IC bypass for flow augmentation demonstrated high patency rates, statistically significantly higher CFIs compared to 1D1R, and improved mRS scores at last clinical follow-up. Additionally, the technique allows a shorter dissection time and preserves blood flow to the scalp. The routine utilization of intraoperative volumetric flow measurements in such surgeries allows a deeper understanding of the hemodynamic impact on individual patients.