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Richard C. E. Anderson, Benjamin Kennedy, Candix L. Yanes, James Garvin, Michael Needle, Peter Canoll, Neil A. Feldstein and Jeffrey N. Bruce

Convection-enhanced delivery (CED) for the treatment of malignant gliomas is a technique that can deliver chemotherapeutic agents directly into the tumor and the surrounding interstitium through sustained, low-grade positive-pressure infusion. This allows for high local concentrations of drug within the tumor while minimizing systemic levels that often lead to dose-limiting toxicity. Diffuse intrinsic pontine gliomas (DIPGs) are universally fatal childhood tumors for which there is currently no effective treatment. In this report the authors describe CED of the topoisomerase inhibitor topotecan for the treatment of DIPG in 2 children.

As part of a pilot feasibility study, the authors treated 2 pediatric patients with DIPG. Stereotactic biopsy with frozen section confirmation of glial tumor was followed by placement of bilateral catheters for CED of topotecan during the same procedure. The first patient underwent CED 210 days after initial diagnosis, after radiation therapy and at the time of tumor recurrence, with a total dose of 0.403 mg in 6.04 ml over 100 hours. Her Karnofsky Performance Status (KPS) score was 60 before CED and 50 posttreatment. Serial MRI initially demonstrated a modest reduction in tumor size and edema, but the tumor progressed and the patient died 49 days after treatment. The second patient was treated 24 days after the initial diagnosis prior to radiation with a total dose of 0.284 mg in 5.30 ml over 100 hours. Her KPS score was 70 before CED and 50 posttreatment. Serial MRI similarly demonstrated an initial modest reduction in tumor size. The patient subsequently underwent fractionated radiation therapy, but the tumor progressed and she died 120 days after treatment.

Topotecan delivered by prolonged CED into the brainstem in children with DIPG is technically feasible. In both patients, high infusion rates (> 0.12 ml/hr) and high infusion volumes (> 2.8 ml) resulted in new neurological deficits and reduction in the KPS score, but lower infusion rates (< 0.04 ml/hr) were well tolerated. While serial MRI showed moderate treatment effect, CED did not prolong survival in these 2 patients. More studies are needed to improve patient selection and determine the optimal flow rates for CED of chemotherapeutic agents into DIPG to maximize safety and efficacy. Clinical trial registration no.: NCT00324844.

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Benjamin C. Kennedy, Taylor B. Nelp, Kathleen M. Kelly, Michelle Q. Phan, Samuel S. Bruce, Michael M. McDowell, Neil A. Feldstein and Richard C. E. Anderson

OBJECT

Chiari malformation Type I (CM-I) is associated with a syrinx in 25%–85% of patients. Although posterior fossa decompression (PFD) without dural opening is an accepted treatment option for children with symptomatic CM-I, many surgeons prefer to open the dura if a syrinx exists. The purpose of this study was to investigate the frequency and timing of syrinx resolution in children undergoing PFD without dural opening for CM-I.

METHODS

A retrospective review of 68 consecutive pediatric patients with CM-I and syringomyelia who underwent PFD without dural opening was conducted. Patient demographics, presenting symptoms and signs, radiographic findings, and intraoperative ultrasound and neuromonitoring findings were studied as well as the patients’ clinical and radiographic follow-up.

RESULTS

During the mean radiographic follow-up period of 32 months, 70% of the syringes improved. Syrinx improvement occurred at a mean of 31 months postoperatively. All patients experienced symptom improvement within the 1st year, despite only 26% of patients showing radiographic improvement during that period. Patients presenting with sensory symptoms or motor weakness had a higher likelihood of having radiographic syrinx improvement postoperatively.

CONCLUSIONS

In children with CM-I and a syrinx undergoing PFD without dural opening, syrinx resolution occurs in approximately 70% of patients. Radiographic improvement of the syrinx is delayed, but this does not correlate temporally with symptom improvement. Sensory symptoms or motor weakness on presentation are associated with syrinx resolution after surgery.

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Travis R. Ladner, Jacob K. Greenberg, Nicole Guerrero, Margaret A. Olsen, Chevis N. Shannon, Chester K. Yarbrough, Jay F. Piccirillo, Richard C. E. Anderson, Neil A. Feldstein, John C. Wellons III, Matthew D. Smyth, Tae Sung Park and David D. Limbrick Jr.

OBJECTIVE

Administrative billing data may facilitate large-scale assessments of treatment outcomes for pediatric Chiari malformation Type I (CM-I). Validated International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code algorithms for identifying CM-I surgery are critical prerequisites for such studies but are currently only available for adults. The objective of this study was to validate two ICD-9-CM code algorithms using hospital billing data to identify pediatric patients undergoing CM-I decompression surgery.

METHODS

The authors retrospectively analyzed the validity of two ICD-9-CM code algorithms for identifying pediatric CM-I decompression surgery performed at 3 academic medical centers between 2001 and 2013. Algorithm 1 included any discharge diagnosis code of 348.4 (CM-I), as well as a procedure code of 01.24 (cranial decompression) or 03.09 (spinal decompression or laminectomy). Algorithm 2 restricted this group to the subset of patients with a primary discharge diagnosis of 348.4. The positive predictive value (PPV) and sensitivity of each algorithm were calculated.

RESULTS

Among 625 first-time admissions identified by Algorithm 1, the overall PPV for CM-I decompression was 92%. Among the 581 admissions identified by Algorithm 2, the PPV was 97%. The PPV for Algorithm 1 was lower in one center (84%) compared with the other centers (93%–94%), whereas the PPV of Algorithm 2 remained high (96%–98%) across all subgroups. The sensitivity of Algorithms 1 (91%) and 2 (89%) was very good and remained so across subgroups (82%–97%).

CONCLUSIONS

An ICD-9-CM algorithm requiring a primary diagnosis of CM-I has excellent PPV and very good sensitivity for identifying CM-I decompression surgery in pediatric patients. These results establish a basis for utilizing administrative billing data to assess pediatric CM-I treatment outcomes.

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Nikita G. Alexiades, Edward S. Ahn, Jeffrey P. Blount, Douglas L. Brockmeyer, Samuel R. Browd, Gerald A. Grant, Gregory G. Heuer, Todd C. Hankinson, Bermans J. Iskandar, Andrew Jea, Mark D. Krieger, Jeffrey R. Leonard, David D. Limbrick Jr., Cormac O. Maher, Mark R. Proctor, David I. Sandberg, John C. Wellons III, Belinda Shao, Neil A. Feldstein and Richard C. E. Anderson

OBJECTIVE

Complications after complex tethered spinal cord (cTSC) surgery include infections and cerebrospinal fluid (CSF) leaks. With little empirical evidence to guide management, there is variability in the interventions undertaken to limit complications. Expert-based best practices may improve the care of patients undergoing cTSC surgery. Here, authors conducted a study to identify consensus-driven best practices.

METHODS

The Delphi method was employed to identify consensual best practices. A literature review regarding cTSC surgery together with a survey of current practices was distributed to 17 board-certified pediatric neurosurgeons. Thirty statements were then formulated and distributed to the group. Results of the second survey were discussed during an in-person meeting leading to further consensus, which was defined as ≥ 80% agreement on a 4-point Likert scale (strongly agree, agree, disagree, strongly disagree).

RESULTS

Seventeen consensus-driven best practices were identified, with all participants willing to incorporate them into their practice. There were four preoperative interventions: (1, 2) asymptomatic AND symptomatic patients should be referred to urology preoperatively, (3, 4) routine preoperative urine cultures are not necessary for asymptomatic AND symptomatic patients. There were nine intraoperative interventions: (5) patients should receive perioperative cefazolin or an equivalent alternative in the event of allergy, (6) chlorhexidine-based skin preparation is the preferred regimen, (7) saline irrigation should be used intermittently throughout the case, (8) antibiotic-containing irrigation should be used following dural closure, (9) a nonlocking running suture technique should be used for dural closure, (10) dural graft overlay should be used when unable to obtain primary dural closure, (11) an expansile dural graft should be incorporated in cases of lipomyelomeningocele in which primary dural closure does not permit free flow of CSF, (12) paraxial muscles should be closed as a layer separate from the fascia, (13) routine placement of postoperative drains is not necessary. There were three postoperative interventions: (14) postoperative antibiotics are an option and, if given, should be discontinued within 24 hours; (15) patients should remain flat for at least 24 hours postoperatively; (16) routine use of abdominal binders or other compressive devices postoperatively is not necessary. One intervention was prioritized for additional study: (17) further study of additional gram-negative perioperative coverage is needed.

CONCLUSIONS

A modified Delphi technique was used to develop consensus-driven best practices for decreasing wound complications after cTSC surgery. Further study is required to determine if implementation of these practices will lead to reduced complications. Discussion through the course of this study resulted in the initiation of a multicenter study of gram-negative surgical site infections in cTSC surgery.