Choroid plexus tumors consist of papillomas and carcinomas. A variety of germline and somatic genetic changes have been demonstrated for each of these subtypes. In this paper, the authors summarize the current knowledge of the genetic bases of these tumors.
Ian D. Kamaly-Asl, Navid Shams and Michael D. Taylor
James S. Walkden, Zsolt Zador, Amit Herwadkar and Ian D. Kamaly-Asl
Over the last 20 years, several intraoperative adjuncts, including ultrasonography, neuronavigation, and angiography, have been said to aid the intraoperative localization and resection of cerebral arteriovenous malformations (AVMs). The authors assessed the value of intraoperative Doppler ultrasonography in conjunction with neuronavigation during surgery for cerebral AVMs in the pediatric population.
The authors reviewed all cranial AVM resections performed by a single surgeon at their institution in the period from 2007 to 2013 and here describe their experience and results in a series of 20 consecutive AVM resections in 19 pediatric patients. Intraoperative Doppler ultrasonography had been used in conjunction with preoperative CT or neuronavigational MRI. Preoperative and postoperative clinical findings, patient age, and Spetzler-Martin AVM grade were identified in all patients.
All patients, whose ages ranged from 2 to 16 years, underwent craniotomy and excision of an AVM, which was supratentorial in 18 cases and infratentorial in 2. Patients in 11 cases underwent preoperative embolization, and all other patients underwent cerebral angiography prior to surgery, except for 2 patients who were urgently surgically treated because of low Glasgow Coma Scale scores and associated hematoma. Spetzler-Martin Grades I (3 cases), II (6), III (7), and IV (4) AVMs were represented in this series. Intraoperative Doppler ultrasound provided high-quality images in all cases and demonstrated the location, size, and flow characteristics of the AVM and any associated hematoma. Delayed postoperative cerebral angiography demonstrated successful AVM resection in all cases. An assessment of clinical outcomes revealed no new long-term neurological deficits at 3 months postoperatively.
Intraoperative Doppler ultrasonography is a reliable and useful tool for intraoperative localization and guidance for AVM resection in the pediatric population. When used in conjunction with neuronavigation equipment and modern microscopes, this technique has shown a very high complete resection rate with extremely low associated morbidity.
Pratipal Kalsi and Nitin Mukerji
Ursalan A. Khan, Amar Bhavsar, Hasan Asif, Konstantina Karabatsou, James R. S. Leggate, Ajit Sofat and Ian D. Kamaly-Asl
Surgeries for CNS tumors are frequently performed by general neurosurgeons and by those who specialize in surgical neurooncology. Subspecialization in neurosurgical practice has become common and may improve patient morbidity and mortality rates. However, the potential benefits for patients of having their surgeries performed by surgical neurooncologists remain unclear. Recently, a shift in patient care to those who practice predominantly surgical neurooncology has been promoted. Evidence for this practice is lacking and therefore requires fundamental investigation.
The authors conducted a case-control study of neurooncology patients who underwent surgery for glioblastoma and anaplastic astrocytoma during 2006–2009. Outcomes were compared for patients whose surgery was performed by general neurosurgeons (generalists) or by specialist neurooncology neurosurgeons (specialists). An electronic record database and a picture archiving and communication system were used to collect data and assess the extent of tumor resection. Mortality rates and survival times were compared. Patient comorbidity and postoperative morbidity were assessed by using the Waterlow, patient handling, and falls risk assessment scores. Effects of case mix were adjusted for by using Cox regression and a hazards model.
Outcomes for 135 patients (65 treated by generalists and 70 by specialists) were analyzed. Survival times were longer for patients whose surgery was performed by specialists (p = 0.026) and after correction for case mix (p = 0.019). Extent of tumor resection was greater when performed by specialists (p = 0.005) and correlated with increased survival times (p = 0.004). There was a trend toward reduced surgical deaths when surgery was performed by specialists (2.8%) versus generalists (7%) (p = 0.102), and inpatient stays were significantly shorter when surgery was performed by specialists (p = 0.008).
The prognosis for glioblastoma multiforme remains dire, and improved treatments are urgently needed. This study provides evidence for a survival benefit when surgery is performed by specialist neurooncology neurosurgeons. The benefit might be attributable to increased tumor resection. Furthermore, specialist neurooncology surgical care may reduce the number of surgical patient deaths and length of inpatient stay. These findings support the recommendations for subspecialization within surgical neurooncology and advocate for care of these patients by specialists.
Zsolt Zador, David J. Coope and Ian D. Kamaly-Asl
Endoscopic third ventriculostomy (ETV) has become a widely used method for CSF diversion when treating obstructive hydrocephalus. There are multiple recommendations on the transcortical ETV entry points, and some are specifically designed to provide a trajectory that avoids displacement to the eloquent periventricular structures. However, the morphology of the ventricular system is highly variable in hydrocephalus, and therefore a single best ETV trajectory may not be applicable to all cases. In the current study, 3 frequently quoted ETV entry points are compared in a cohort of pediatric cases with different degrees of ventriculomegaly.
The images of 30 consecutive pediatric patients with varying degrees of ventriculomegaly were reviewed. Three-dimensional models were created using radiological analysis of anatomical detail and preoperative MRI scans in order to simulate 3 frequently quoted ETV trajectories for rigid neuroendoscopes. These trajectories were characterized based on the frequency and depth of tissue displacement to structures such as the fornix, caudate nucleus, genu of the internal capsule, and thalamus. The results are stratified based on ventricle size using the frontal horn ratio (FHR).
Eloquent areas were displaced in nearly all analyzed entry points (97%–100%). Stratifying the data based on ventricle size revealed that 1) lateral structures were more likely to be displaced in cases of intermediate ventriculomegaly (FHR < 0.4) using all 3 trajectories, whereas 2) the fornix was less likely to be displaced using more posteriorly placed trajectories for severe ventriculomegaly (FHR > 0.4). Allowing for minimal (2.4 mm) tissue displacement, a more posterior entry point was less traumatic for severe ventriculomegaly.
There is no single best ETV trajectory that fully avoids displacement of the eloquent periventricular structures. Larger ventricles require a more posteriorly placed entry point in order to reduce injury to the eloquent structures, and intermediate ventricles would dictate a medial entry point. These results suggest that the optimal entry point should be selected on a case-by-case basis after incorporating ventricle size.
Nii K. Addo, Ian D. Kamaly-Asl, Vivek A. Josan, Anna M. Kelsey and Edward J. Estlin
The authors report the case of a 14-month-old boy with a large right intraventricular choroid plexus papilloma (CPP) for which the first attempt at resection resulted in life-threatening intraoperative hemorrhage. The tumor was unsuitable for embolization, and neoadjuvant ifosfamide, carboplatin, etoposide (ICE) chemotherapy had no effect on tumor size. However, chemotherapy with vincristine, although not impacting on CT perfusion parameters, resulted in a significant decrease in tumor size, enabling complete resection with manageable blood loss. The mechanism underlying the effect of vincristine in this case is uncertain, but it is a treatment strategy that warrants further evaluation for the treatment of CPPs that are not amenable to embolization.
Lucie Lafay-Cousin, Donald J. Mabbott, William Halliday, Michael D. Taylor, Uri Tabori, Ian D. Kamaly-Asl, Abhaya V. Kulkarni, Ute Bartels, Mark Greenberg and Eric Bouffet
Choroid plexus carcinomas (CPCs) are rare pediatric tumors with a generally poor prognosis. Although the role of surgery is well recognized, the role of adjuvant chemotherapy and radiation therapy remains unclear. In this paper, the authors' goal was to assess the role of second-look surgery and neoadjuvant ifosfamide, carboplatin, etoposide (ICE) chemotherapy in the management of CPC and to study neurocognitive outcome.
The authors performed an institutional retrospective review of patients in whom CPC was diagnosed between 1985 and 2006 at the Hospital for Sick Children in Toronto. Fourteen patients (7 boys and 7 girls) were included. The median age at diagnosis was 18.6 months (range 1.1–65.3 months). Four patients had evidence of metastatic disease at diagnosis. Two of the 14 patients underwent gross-total resection during initial surgery; 12 of the patients received neoadjuvant chemotherapy, 10 of whom underwent second surgery. In total, of 12 patients who received chemotherapy with a curative intent, 11 underwent a greater than 95% resection. Neoadjuvant ICE chemotherapy was given prior to second surgery (median 4 cycles, range 2–5 cycles) and was continued after second resection for a median total of 7 cycles (range 4–16 cycles).
No tumor progression was observed during chemotherapy prior to second surgery. Five patients subsequently experienced tumor progression/relapse. At a median follow-up of 6.9 years (range 1.9–18.5 years), 8 patients are alive. None of the survivors received radiation therapy. However, 6 of 8 display significant neurocognitive and/or sensorial deficit.
In this experience, second surgery following neoadjuvant ICE chemotherapy led to a high rate of complete or near-complete resection. Chemotherapy appears to facilitate second-look surgery, in particular through a reduction of intraoperative blood loss. Despite radiation avoidance, the majority of survivors experienced significant neurocognitive impairment.
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
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.
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.
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.
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.