Resection Of Pediatric Brain Tumors Research Articles

Improving advanced intraoperative MRI methods during pediatric neurosurgery.

Advanced intraoperative MR images (ioMRI) acquired during the resection of pediatric brain tumors could offer additional physiological information to preserve healthy tissue. With this work, we aimed to develop a protocol for ioMRI with increased sensitivity for arterial spin labeling (ASL) and diffusion MRI (dMRI), optimized for patient positioning regularly used in the pediatric neurosurgery setting. For ethical reasons, ASL images were acquired in healthy adult subjects that were imaged in the prone and supine position. After this, the ASL cerebral blood flow (CBF) was quantified and compared between both positions. To evaluate the impact of the RF coils setups on image quality, we compared different setups (two vs. four RF coils) by looking at T1-weighted (T1w) signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR), as well as undertaking a qualitative evaluation of T1w, T2w, ASL, and dMR images. Mean ASL CBF did not differ between the surgical prone and supine positions in any of the investigated regions of interest or the whole brain. T1w SNR (gray matter: p = 0.016, 34% increase; white matter: p = 0.016, 32% increase) and CNR were higher (p = 0.016) in the four versus two RF coils setups (18.0± 1.8 vs. 13.9± 1.8). Qualitative evaluation of T1w, T2w, ASL, and dMR images resulted in acceptable to good image quality and did not differ statistically significantly between setups. Only the nonweighted diffusion image maps and corticospinal tract reconstructions yielded higher image quality and reduced susceptibility artifacts with four RF coils. Advanced ioMRI metrics were more precise with four RF coils as the standard deviation decreased. Taken together, we have investigated the practical use of advanced ioMRI during pediatric neurosurgery. We conclude that ASL CBF quantification in the surgical prone position is valid and that ASL and dMRI acquisition with two RF coils can be performed adequately for clinical use. With four versus two RF coils, the SNR of the images increases, and the sensitivity to artifacts reduces.

Anatomical step-by-step dissection of common approaches to the third ventricle for trainees: surgical anatomy of the anterior transcortical and interhemispheric transcallosal approaches, surgical principles, and illustrative pediatric cases.

To create a high-quality, cadaver-based, operatively oriented resource documenting the anterior transcortical and interhemispheric transcallosal approaches as corridors to the third ventricle targeted towards neurosurgical trainees at all levels. Two formalin-fixed, latex-injected specimens were dissected under microscopic magnification and endoscopic-assisted visualization. Dissections of the transcortical and transcallosal craniotomies with transforaminal, transchoroidal, and interforniceal transventricular approaches were performed. The dissections were documented in a stepwise fashion using three-dimensional photographic image acquisition techniques and supplemented with representative cases to highlight pertinent surgical principles. The anterior transcortical and interhemispheric corridors afford excellent access to the anterior two-thirds of the third ventricle with varying risks associated with frontal lobe versus corpus callosum disruption, respectively. The transcortical approach offers a more direct, oblique view of the ipsilateral lateral ventricle, whereas the transcallosal approach readily establishes biventricular access through a paramedian corridor. Once inside the lateral ventricle, intraventricular angled endoscopy further enhances access to the extreme poles of the third ventricle from either open transcranial approach. Subsequent selection of either the transforaminal, transchoroidal, or interforniceal routes can be performed through either craniotomy and is ultimately dependent on individual deep venous anatomy, the epicenter of ventricular pathology, and the concomitant presence of hydrocephalus or embryologic cava. Key steps described include positioning and skin incision; scalp dissection; craniotomy flap elevation; durotomy; transcortical versus interhemispheric dissection with callosotomy; the aforementioned transventricular routes; and their relevant intraventricular landmarks. Approaches to the ventricular system for maximal safe resection of pediatric brain tumors are challenging to master yet represent foundational cranial surgical techniques. We present a comprehensive operatively oriented guide for neurosurgery residents that combines stepwise open and endoscopic cadaveric dissections with representative case studies to optimize familiarity with third ventricle approaches, mastery of relevant microsurgical anatomy, and preparation for operating room participation.

Rapid intraoperative diagnosis of pediatric brain tumors using Raman spectroscopy: A machine learning approach

BackgroundSurgical resection is a mainstay in the treatment of pediatric brain tumors to achieve tissue diagnosis and tumor debulking. While maximal safe resection of tumors is desired, it can be challenging to differentiate normal brain from neoplastic tissue using only microscopic visualization, intraoperative navigation, and tactile feedback. Here, we investigate the potential for Raman spectroscopy (RS) to accurately diagnose pediatric brain tumors intraoperatively.MethodsUsing a rapid acquisition RS device, we intraoperatively imaged fresh ex vivo brain tissue samples from 29 pediatric patients at the Lucile Packard Children’s Hospital between October 2018 and March 2020 in a prospective fashion. Small tissue samples measuring 2-4 mm per dimension were obtained with each individual tissue sample undergoing multiple unique Raman spectra acquisitions. All tissue samples from which Raman spectra were acquired underwent individual histopathology review. A labeled dataset of 678 unique Raman spectra gathered from 160 samples was then used to develop a machine learning model capable of (1) differentiating normal brain from tumor tissue and (2) normal brain from low-grade glioma (LGG) tissue.ResultsTrained logistic regression model classifiers were developed using our labeled dataset. Model performance was evaluated using leave-one-patient-out cross-validation. The area under the curve (AUC) of the receiver-operating characteristic (ROC) curve for our tumor vs normal brain model was 0.94. The AUC of the ROC curve for LGG vs normal brain was 0.91.ConclusionsOur work suggests that RS can be used to develop a machine learning-based classifier to differentiate tumor vs non-tumor tissue during resection of pediatric brain tumors.

SURG-10. SPECTROSCOPIC MEASUREMENT OF 5-ALA-INDUCED INTRACELLULAR PROTOPORPHYRIN IX IN PEDIATRIC BRAIN TUMORS

OBJECTIVE5-ALA guided resection of glioma in adults enables better delineation between tumor and normal brain, allowing improved resection and improved patients’ outcome. Recently, several reports were published regarding 5-ALA for resection of pediatric brain tumors. The aim of the study was to determine the intracellular fluorescence of PPIX in pediatric brain tumors by hyperspectral imaging and to compare it with visually observed intraoperative fluorescence.METHODS5-ALA was administered orally four hours prior to surgery. During tumor resection the surgeon assessed the fluorescence signal to be strong, weak or absent. Subsequently, fluorescence intensity of samples was measured via spectroscopy. In addition, clinical data, imaging and laboratory data were analyzed.RESULTSEleven children (1–16 years) were operated. Tumor entities included: three medulloblastomas, two pilocytic astrocytomas (PA), two anaplastic ependymomas and one diffuse astrocytoma, anaplastic astrocytoma, pilomyxoid astrocytoma and anaplastic pleomorphic xanthoastrocytoma. Strong fluorescence was visible in all anaplastic tumors and one PA; one PA demonstrated weak fluorescence. Visible fluorescence was strongly associated with intracellular fluorescence intensity and PPIX concentration (P<0.05). Within all tumors with visible fluorescence the intracellular PPIX concentration was greater than 4 µg/ml. Except for moderate and transient elevation of liver enzymes, no 5-ALA related adverse events were reported.CONCLUSIONWe demonstrate a strong association between intraoperative observations and spectrometric measurements of PPIX fluorescence in tumor tissue. As in former studies, fluorescence signal was more commonly observed in malignant glial tumors. Further prospective controlled trials should be conducted to investigate the feasibility of 5-ALA guided resection of pediatric brain tumors.

Caregiver-provider communication after resection of pediatric brain tumors.

Because caregivers are a crucial part of a child's medical care, it is important to understand how to best communicate with them during hospitalization. Qualitative research can elucidate the best strategies for effective parent-provider communication. This study aims to reveal communication styles of neurosurgery team members, and to identify areas for improvement in the future. Caregivers of children with a newly diagnosed brain tumor requiring neurosurgery were enrolled during their child's hospitalization. During routine follow-up clinic visits within 3 months after diagnosis and tumor resection, caregivers participated in a semistructured interview, which assessed the quality of communication with the neurosurgery and oncology teams during hospitalization. Interviews were audio-recorded, transcribed, and coded for common themes until thematic saturation was reached. During caregiver interviews (N = 22), several domains were discussed including communicating the diagnosis to the patient and siblings, to the rest of the family/support network, and with the neurosurgery team. Regarding parent-neurosurgeon communication, 82% of caregivers identified at least one positive aspect and 55% identified at least one negative aspect of communication. Caregivers who provided positive feedback appreciated that their neurosurgeon was thorough (73%), direct (27%), or compassionate (14%). They also valued when providers would speak "on my level" (18%) and would speak directly to the patient (27%). In terms of negative feedback, caregivers identified miscommunications (32%), discussing the diagnosis in front of the child before feeling prepared to do so (14%), and a lack of clarity about expectations, medications, or treatment (32%). These data provide specific ways in which neurosurgery providers have communicated effectively with caregivers and identify areas for improvement. Results have been used to develop a navigator-led intervention geared toward improving parent-provider communication during hospitalization for resection of a brain tumor.

The Impact of Intraoperative Electrocorticography on Seizure Outcome After Resection of Pediatric Brain Tumors: A Cohort Study.

Intraoperative electrocorticography (ECoG) has been utilized in patients with tumor-associated seizures; however, its effectiveness for seizure control remains controversial. To evaluate clinical outcomes in pediatric patients undergoing lesionectomy with or without ECoG. Patients undergoing brain tumor resection at Boston Children's Hospital were examined retrospectively (2005-2014). Inclusion criteria involved diagnosis of a supratentorial tumor,≥2 unequivocal seizures, and≥6 mo follow-up. Patients with isolated cortical dysplasia or posterior fossa tumors were excluded. Logistic regression models evaluated predictors of ECoG use, and the impact of ECoG, gross total resection, and focal cortical dysplasia with tumors on seizure freedom by Engel Class and anti-epileptic drug use (AED). A total of 119 pediatric patients were included (n=69 males, 58%; median age, 11.3 yr). Forty-one patients (34.5%) had ECoG-guided surgery. Preoperative seizure duration and number and duration of AED use were significant predictors for undergoing ECoG. There were no differences in seizure freedom (Engel Class I) or improved Engel Score (Class I-II vs III-IV) in patients who did or did not have ECoG at 30 d, 6 mo, and 1, 2, or 5 yr. Patients undergoing ECoG required a greater number of AEDs at 6 mo (P=.01), although this difference disappeared at subsequent time intervals. Gross total resection predicted seizure freedom at 30 d and 6 mo postsurgery (P=.045). This retrospective study, one of the largest evaluating the use of ECoG during tumor resection, suggests that ECoG does not provide improved seizure freedom compared to lesionectomy alone for children.

Spectroscopic measurement of 5-ALA-induced intracellular protoporphyrin IX in pediatric brain tumors.

5-Aminolevulinic acid (5-ALA)-guided resection of gliomas in adults enables better delineation between tumor and normal brain, allowing improved resection and improved patients' outcome. Recently, several reports were published regarding 5-ALA for resection of pediatric brain tumors. The aim of the study was to determine the intracellular fluorescence of protoporphyrin IX (PPIX) in pediatric brain tumors by hyperspectral imaging and to compare it with visually observed intraoperative fluorescence. 5-ALA was administered orally 4h prior to surgery. During tumor resection, the surgeon assessed the fluorescence signal to be strong, weak, or absent. Subsequently, fluorescence intensity of tumor samples was measured via spectroscopy. In addition, clinical data, imaging, and laboratory data were analyzed. Eleven children (1-16years) were operated. Tumor entities included three (n = 3) medulloblastomas, two (n = 2) pilocytic astrocytomas (PA), two (n = 2) anaplastic ependymomas and one (n = 1) diffuse astrocytoma, anaplastic astrocytoma (n = 1), pilomyxoid astrocytoma (n = 1) and anaplastic pleomorphic xanthoastrocytoma (n = 1). Strong fluorescence was visible in all anaplastic tumors and one PA; one PA demonstrated weak fluorescence. Visible fluorescence was strongly associated with intracellular fluorescence intensity and PPIX concentration (P < 0.05). Within all tumors with visible fluorescence, the intracellular PPIX concentration was greater than 4μg/ml. Except for moderate and transient elevation of liver enzymes, no 5-ALA related adverse events were reported. We demonstrate a strong association between intraoperative observations and spectrometric measurements of PPIX fluorescence in tumor tissue. As in former studies, fluorescence signal was more commonly observed in malignant glial tumors. Further prospective controlled trials should be conducted to investigate the feasibility of 5-ALA-guided resection of pediatric brain tumors.

5-ALA fluorescence-guided surgery in pediatric brain tumors-a systematic review.

5-Aminolevulinic acid (5-ALA)-guided resection of gliomas in adults enables better differentiation between tumor and normal brain tissue, allowing a higher degree of resection, and improves patient outcomes. In recent years, several reports have emerged regarding the use of 5-ALA in other brain tumor entities, including pediatric brains tumors. Since gross total resection (GTR) of many brain tumors in children is crucial and the role of 5-ALA-guided resection of these tumors is not clear, we sought to perform a comprehensive literature review on this topic. A systematic literature review of EMBASE and MEDLINE/PubMed databases revealed 19 eligible publications encompassing 175 5-ALA-guided operations on pediatric brain tumors. To prevent bias, publications were revised independently by two authors. We found that 5-ALA-guided resection enabled the surgeons to identify the tumor more easily and was considered helpful mainly in cases of glioblastoma (GBM, 21/27, 78%), anaplastic ependymoma WHO grade III (10/14, 71%), and anaplastic astrocytoma (4/6, 67%). In contrast, cases of pilocytic astrocytomas (PAs) and medulloblastomas 5-ALA-guided surgery did not show consistent fluorescent signals and 5-ALA was considered helpful only in 12% and 22% of cases, respectively. Accumulation of fluorescent porphyrins seems to depend on WHO tumor grading. One important finding is that when 5-ALA-guided resections were considered helpful, the degree of resection was higher than is cases where it was not helpful. The rate of adverse events related to 5-ALA was negligible, especially new postoperative sequelae. 5-ALA could play a role in resection of pediatric brain tumors. However, further prospective clinical trials are needed.

The use of 5-aminolevulinic acid in resection of pediatric brain tumors: a critical review.

The compound, 5-aminolevulinic acid (5-ALA) is approved for fluorescence-guided resections of malignant gliomas in Europe and other countries for use in adults, but not for children. The application of 5-ALA in children remains an off-label use. Several case reports on fluorescence-guided surgery use in children have been published, yet no prospective study has been conducted. Here we systematically review the reported studies and discuss the usefulness, application, and safety of 5-ALA use in resection of pediatric brain tumors.

Resection of Pediatric Brain Tumors: Intraoperative Ultrasound Revisited.

Background:Extent of resection is a very important prognostic marker in most pediatric brain tumors. Intraoperative imaging facilitates resection control. Intraoperative ultrasound (IOUS) is a cost-effective alternative to intraoperative magnetic resonance, but scant literature addresses its utility in this context.Methods:We retrospectively reviewed all pediatric brain tumors operated at our center using navigated three-dimensional ultrasound (US). The utility of the US in resection control was recorded and extent of resection evaluated.Results:IOUS was used in 20 cases (3 for frameless biopsy and 17 for tumor resection control). It was 100% accurate in localizing all tumors and yielded 100% diagnosis in the biopsy cases. Technical limitations precluded its use in 2 of the 17 cases of tumor resection. In the remaining 15, it correctly predicted the residual tumor status in 13 cases (87%). A gross total resection was achieved overall in 12 cases (80%) with postoperative morbidity in only one case.Conclusions:IOUS is a useful tool to localize intracranial tumors and guide the resection reliably. Widespread use can improve its applicability and make it an effective intraoperative imaging tool in pediatric brain tumors.

Fluorescence-guided surgery with 5-aminolevulinic acid for resection of brain tumors in children—a technical report

5-aminolevulinic acid (5-ALA) can be used as an adjunct for the surgery of adult malignant glioma and improves the rate of gross total resection and patient survival. So far, only three casuistic reports of fluorescence-guided surgery used in children have been published. We report our pilot series of 16 pediatric brain tumors treated with 5-ALA. Sixteen patients (mean age 9 years, range 1-16 years) received a standardized 5-ALA dose according to the published protocol after informed parental consent. The fluorescence status (positive versus negative) in correlation with histology as well as blood samples and adverse clinical symptoms were recorded. Histology revealed pilocytic astrocytoma (n = 7), classical medulloblastoma (n = 4), anaplastic astrocytoma (n = 1), glioblastoma (n = 3) and anaplastic ependymoma (n = 1). Positive fluorescence was observed in cases of anaplastic astrocytoma, glioblastoma, and medulloblastoma, respectively. Significant increases were registered for alanine aminotransferase (14.92 ± 1.106 U/l vs. 37.70 ± 3.795 U/l, P = 0.0020) and gamma glutamyl transpeptidase (12.69 ± 1.638 U/l vs. 39.29 ± 6.342 U/l, P = 0.0156), correlated with young age. No further adverse reactions were evident. Positive fluorescence was observed in two high-grade gliomas and one medulloblastoma after oral administration of 5-ALA. Thus, 5-ALA appears capable of inducing fluorescence in pediatric high-grade tumors. Adverse reactions observed in children were similar to those reported for adults, although very young children might be at increased risk. Further studies are required to elucidate pharmacokinetic and pharmacodynamic properties of 5-ALA in children and to assess its prognostic role in the resection of pediatric brain tumors.

The use of 5-aminolevulinic acid fluorescence guidance in resection of pediatric brain tumors

Whereas in the adult population 5-Aminolevulinic acid (5-ALA) fluorescence guidance has been widely accepted for improving the extent of tumor resection, the application in children remains an off-label use. Even though most pediatric study protocols require a complete resection for improving outcome parameters, only few pediatric patients have been operated with fluorescence guidance, and it remains questionable, whether and which pediatric tumors show useful fluorescence. We present casuistic reports of application of 5-ALA in children collected from three different neurosurgical departments. In children with suspected malignant intracerebral tumor or recurrence, individual informed consent was obtained in each case from the parents. 5-ALA was administered according to the adult protocol, with 20 mg/kg, 2 h before induction of anesthesia. We retrospectively analyzed 18 patients (13 male, 5 female; age 3-18 years), using the intraoperative neurosurgical protocol, the postoperative MRI results, and the follow-up clinical examinations. The use of 5-ALA fluorescence guidance proved to be safe in our group of pediatric patients. Fluorescence guidance was most useful for recurrent glioblastoma resection. Medulloblastoma tissue displayed fluorescence only inconsistently, and most pilocytic astrocytoma remained without staining. Ganglioglioma showed partial staining in the central tumor areas, without allowing the use for circumferent resection. The off-label use of 5-ALA fluorescence guidance in pediatric patients appears to be most useful in recurrent high-grade gliomas. Fluorescence accumulation in other pediatric brain tumor entities is not predictable and should be evaluated in future clinical studies before being integrated into the current treatment protocols.

Role of intraoperative ultrasound in resection of pediatric brain tumors

In neurosurgery, ultrasound is useful in determination of the tumor location, differentiation between solid tumors and cystic components, as well as definition of the shortest and safest access to the mass. This study aims to evaluate the role of the intraoperative ultrasound in resection of pediatric brain tumors. Intraoperative ultrasonography (conventional B-Mode) was performed in 25 pediatric patients with brain tumors pre-, during, and post-resection, in whom eight patients were supratentorial and 17 were infratentorial. Post-op Grayscale images of the brain tumors on conventional ultrasound were compared with the results of immediate postoperative magnetic resonance imaging. The border of the tumor and post-resection residual tumor were more distinguishable from healthy brain on ultrasound during the operation. Improved definition of the tumor tissue from normal brain with ultrasound was demonstrated in all cases aiding in tumor resection. Intraoperative ultrasound is suggested to be a useful imaging technique in defining the border between the tumor and healthy brain tissue pre-resection, in detecting residual tumor tissues after the resection of the mass, and in guiding to the shortest and safest access to the tumor during neurosurgery.

Craniotomy for resection of pediatric brain tumors in the United States, 1988 to 2000: effects of provider caseloads and progressive centralization and specialization of care.

Large provider caseloads are associated with better patient outcomes after many complex surgical procedures. Mortality rates for pediatric brain tumor surgery in various practice settings have not been described. We used a national hospital discharge database to study the volume-outcome relationship for craniotomy performed for pediatric brain tumor resection, as well as trends toward centralization and specialization. We conducted a cross sectional and longitudinal cohort study using Nationwide Inpatient Sample data for 1988 to 2000 (Agency for Healthcare Research and Quality, Rockville, MD). Multivariate analyses adjusted for age, sex, geographic region, admission type (emergency, urgent, or elective), tumor location, and malignancy. We analyzed 4712 admissions (329 hospitals, 480 identified surgeons) for pediatric brain tumor craniotomy. The in-hospital mortality rate was 1.6% and decreased from 2.7% (in 1988-1990) to 1.2% (in 1997-2000) during the study period. On a per-patient basis, median annual caseloads were 11 for hospitals (range, 1-59 cases) and 6 for surgeons (range, 1-32 cases). In multivariate analyses, the mortality rate was significantly lower at high-volume hospitals than at low-volume hospitals (odds ratio, 0.52 for 10-fold larger caseload; 95% confidence interval, 0.28-0.94; P = 0.03). The mortality rate was 2.3% at the lowest-volume-quartile hospitals (4 or fewer admissions annually), compared with 1.4% at the highest-volume-quartile hospitals (more than 20 admissions annually). There was a trend toward lower mortality rates after surgery performed by high-volume surgeons (P = 0.16). Adverse hospital discharge disposition was less likely to be associated with high-volume hospitals (P < 0.001) and high-volume surgeons (P = 0.004). Length of stay and hospital charges were minimally related to hospital caseloads. Approximately 5% of United States hospitals performed pediatric brain tumor craniotomy during this period. The burden of care shifted toward large-caseload hospitals, teaching hospitals, and surgeons whose practices included predominantly pediatric patients, indicating progressive centralization and specialization. Mortality and adverse discharge disposition rates for pediatric brain tumor craniotomy were lower when the procedure was performed at high-volume hospitals and by high-volume surgeons in the United States, from 1988 to 2000. There were trends toward lower mortality rates, greater centralization of surgery, and more specialization among surgeons during this period.

Craniotomy for Resection of Pediatric Brain Tumors in the United States, 1988 to 2000: Effects of Provider Caseloads and Progressive Centralization and Specialization of Care???.Edward R. Smith, M.D., William E. Butler, M.D., Fred G. Barker II, M.D.

Craniotomy for Resection of Pediatric Brain Tumors in the United States, 1988 to 2000: Effects of Provider Caseloads and Progressive Centralization and Specialization of Care???.Edward R. Smith, M.D., William E. Butler, M.D., Fred G. Barker II, M.D.

Craniotomy for Resection of Pediatric Brain Tumors in the United States, 1988 to 2000: Effects of Provider Caseloads and Progressive Centralization and Specialization of Care….Edward R. Smith, M.D., William E. Butler, M.D., Fred G. Barker II, M.D.

Craniotomy for Resection of Pediatric Brain Tumors in the United States, 1988 to 2000: Effects of Provider Caseloads and Progressive Centralization and Specialization of Care….Edward R. Smith, M.D., William E. Butler, M.D., Fred G. Barker II, M.D.

Computer Assisted Stereotactic Biopsy and Volumetric Resection of Pediatric Brain Tumors

Like adults, children may undergo stereotactic CT, MRI, and digital angiography with their heads fixed in an imaging compatible head holder. Tumor volumes are digitized from stereotactic CT and MRI slice images. The tumor volume can then be sliced perpendicular to the surgical view line, which is the surgical approach expressed in terms of angular settings on the stereotactic instrument. These sliced images are displayed on a computer monitor in the operating room and are used to guide the surgery and help the surgeon identify the plane between tumor and surrounding brain tissue.