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Christian Schneider, Ian Kamaly-Asl, Vijay Ramaswamy, Lucie Lafay-Cousin, Abhaya V. Kulkarni, James T. Rutka, Marc Remke, Daniel Coluccia, Uri Tabori, Cynthia Hawkins, Eric Bouffet and Michael D. Taylor

OBJECT

Choroid plexus carcinomas (CPCs) are rare brain tumors originating from the ventricular choroid plexus. They account for 2%–4% of all pediatric brain tumors and are most frequently seen in very young children. This pediatric proclivity, in combination with a marked vascularity, renders an aggressive resection a difficult and often dangerous endeavor. Blood losses of several total blood volumes in small children are not uncommon, sometimes forcing the neurosurgeon to abort the procedure, often leaving residual tumor. Great extent of tumor resection is an accepted beneficial factor for overall survival. Therefore, a second resection usually follows the administration of adjuvant chemotherapy. Second-look surgery appears to be associated with markedly decreased blood loss. Histological examination of specimens obtained at a second intervention shows decreased vascularity and fibrotic changes in tumor tissue. At the Hospital for Sick Children in Toronto, this empirical finding led to the strategy of neoadjuvant chemotherapy to minimize blood loss and maximize cytoreduction. The authors undertook this study to assess the potentially beneficial effect of neoadjuvant chemotherapy on blood loss during surgery for CPCs.

METHODS

In this retrospective cohort review, the demographic, clinical, and treatment parameters of 22 consecutive patients diagnosed with CPC are presented. All underwent surgical treatment at the Hospital for Sick Children from 1982 to 2013. Special attention was given to the impact of neoadjuvant chemotherapy on extent of resection and intraoperative blood loss. Extent of resection was calculated based on perioperative neuroimaging, and amount of blood loss was estimated based on transfusion parameters and perioperative changes in hematocrit.

RESULTS

Ten patients did not receive neoadjuvant chemotherapy, and 12 were treated with 2–5 cycles of ICE (ifosfamide, carboplatin, etoposide) chemotherapy in a neoadjuvant fashion. The 22 patients included in the study underwent a total of 37 tumor resection surgeries. In all of the cases in which neoadjuvant chemotherapy was used, at least a near-total resection (> 95% of tumor volume) was achieved. Patients who underwent gross-total resection had prolonged overall survival. Of the 37 resections, 18 were performed after chemotherapy. Mean blood loss in the neoadjuvant chemotherapy group was 22% of total estimated blood volume as opposed to 96% in patients without preoperative chemotherapy.

CONCLUSIONS

In children with CPC, the administration of neoadjuvant chemotherapy decreases intraoperative blood loss and increases extent of resection with a significant positive effect on overall survival.

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Roberto Jose Diaz, Roberto Rey Dios, Eyas M. Hattab, Kelly Burrell, Patricia Rakopoulos, Nesrin Sabha, Cynthia Hawkins, Gelareh Zadeh, James T. Rutka and Aaron A. Cohen-Gadol

OBJECT

Intravenous fluorescein sodium has been used during resection of high-grade gliomas to help the surgeon visualize tumor margins. Several studies have reported improved rates of gross-total resection (GTR) using high doses of fluorescein sodium under white light. The recent introduction of a fluorescein-specific camera that allows for high-quality intraoperative imaging and use of very low dose fluorescein has drawn new attention to this fluorophore. However, the ability of fluorescein to specifically stain glioma cells is not yet well understood.

METHODS

The authors designed an in vitro model to assess fluorescein uptake in normal human astrocytes and U251 malignant glioma cells. An in vivo experiment was also subsequently designed to study fluorescein uptake by intracranial U87 malignant glioma xenografts in male nonobese diabetic/severe combined immunodeficient mice. A genetically induced mouse glioma model was used to adjust for the possible confounding effect of an inflammatory response in the xenograft model. To assess the intraoperative application of this technology, the authors prospectively enrolled 12 patients who underwent fluorescein-guided resection of their high-grade gliomas using low-dose intravenous fluorescein and a microscope-integrated fluorescence module. Intraoperative fluorescent and nonfluorescent specimens at the tumor margins were randomly analyzed for histopathological correlation.

RESULTS

The in vitro and in vivo models suggest that fluorescein demarcation of glioma-invaded brain is the result of distribution of fluorescein into the extracellular space, most likely as a result of an abnormal blood-brain barrier. Glioblastoma tumor cell–specific uptake of fluorescein was not observed, and tumor cells appeared to mostly exclude fluorescein. For the 12 patients who underwent resection of their high-grade gliomas, the histopathological analysis of the resected specimens at the tumor margin confirmed the intraoperative fluorescent findings. Fluorescein fluorescence was highly specific (up to 90.9%) while its sensitivity was 82.2%. False negatives occurred due to lack of fluorescence in areas of diffuse, low-density cellular infiltration. Margins of contrast enhancement based on intraoperative MRI–guided StealthStation neuronavigation correlated well with fluorescent tumor margins. GTR of the contrast-enhancing area as guided by the fluorescent signal was achieved in 100% of cases based on postoperative MRI.

CONCLUSIONS

Fluorescein sodium does not appear to selectively accumulate in astrocytoma cells but in extracellular tumor cell-rich locations, suggesting that fluorescein is a marker for areas of compromised blood-brain barrier within high-grade astrocytoma. Fluorescein fluorescence appears to correlate intraoperatively with the areas of MR enhancement, thus representing a practical tool to help the surgeon achieve GTR of the enhancing tumor regions.

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Christian Schneider, Vijay Ramaswamy, Abhaya V. Kulkarni, James T. Rutka, Marc Remke, Uri Tabori, Cynthia Hawkins, Eric Bouffet and Michael D. Taylor

OBJECT

While medulloblastoma was initially thought to comprise a single homogeneous entity, it is now accepted that it in fact comprises 4 discrete subgroups, each with its own distinct demographics, clinical presentation, transcriptomics, genetics, and outcome. Hydrocephalus is a common complication of medulloblastoma and not infrequently requires CSF diversion. The authors report the incidence of CSF diversion surgery in each of the subgroups of medulloblastoma (Wnt, Shh, Group 3, and Group 4).

METHODS

The medical and imaging records for patients who underwent surgery for medulloblastoma at The Hospital for Sick Children were retrospectively reviewed. The primary outcome was the requirement for CSF diversion surgery either before or within 60 days of tumor resection. The modified Canadian Preoperative Prediction Rule for Hydrocephalus (mCPPRH) was compared among subgroups.

RESULTS

Of 143 medulloblastoma patients, treated from 1991 to 2013, sufficient data were available for 130 patients (15 with Wnt, 30 with Shh, 30 with Group 3, and 55 with Group 4 medulloblastomas). Of these, 28 patients (22%) ultimately underwent CSF diversion surgery: 0% with Wnt, 29% with Shh, 29% with Group 3, and 43% with Group 4 tumors. Patients in the Wnt subgroup had a lower incidence of CSF diversion than all other patients combined (p = 0.04). Wnt patients had a lower mCPPRH score (lower risk of CSF diversion, p = 0.045), were older, had smaller ventricles at diagnosis, and had no leptomeningeal metastases.

CONCLUSIONS

The overall rate of CSF diversion surgery for Shh, Group 3, and Group 4 medulloblastomas is around 30%, but no patients in the present series with a Wnt medulloblastoma required shunting. The low incidence of hydrocephalus in patients with Wnt medulloblastoma likely reflects both host factors (age) and disease factors (lack of metastases). The absence of hydrocephalus in patients with Wnt medulloblastomas likely contributes to their excellent rate of survival and may also contribute to a higher quality of life than for patients in other subgroups.