Pathology and genetics of tumours of the nervous system

Purpose The optimal management of craniopharyngiomas remains controversial, especially in children and young adults. This study reports a single institution's experience with such patients. Methods and materials Between 1974 and 2001, 76 patients were treated for craniopharyngioma at the Children's Hospital of Philadelphia and the Hospital of University of Pennsylvania (HUP). Of these, 75 patients (97%) were evaluable with long-term follow-up. Although all patients underwent attempted gross total resection, 27 had documentation of less than total resection with 18 of these patients receiving immediate postoperative radiotherapy (RT). An additional 22 patients received RT at HUP after failing surgery alone. Results Median follow-up for all patients was 7.6 years. The 10-year actuarial overall survival, relapse-free survival, and local control (LC) rates for all patients were 85%, 48%, and 53%, respectively. When comparing the 57 patients treated with surgery alone to the 18 treated with subtotal resection (STR) followed by RT, a significant difference in LC rates at 10 years (42% vs. 84%, respectively; p = 0.004) was noted. However, no statistically significant difference in overall survival was found between the two groups, because RT was highly effective as salvage therapy. Twenty-two patients at HUP treated with RT after relapse had a 10-year ultimate LC rate comparable to that of patients who received RT immediately after STR. Conclusion RT given either immediately after STR or at relapse is effective in controlling craniopharyngiomas.

Surgery with or without radiation therapy in the management of craniopharyngiomas in children and young adults

Ependymal tumors are rare CNS tumors and may occur at any age, but their proportion among primary brain tumors is highest in children and young adults. Thus, the level of evidence of diagnostic and therapeutic interventions is higher in the pediatric compared with the adult patient population.The diagnosis and disease staging is performed by craniospinal MRI. Tumor classification is achieved by histological and molecular diagnostic assessment of tissue specimens according to the World Health Organization (WHO) classification 2016. Surgery is the crucial initial treatment in both children and adults. In pediatric patients with intracranial ependymomas of WHO grades II or III, surgery is followed by local radiotherapy regardless of residual tumor volume. In adults, radiotherapy is employed in patients with anaplastic ependymoma WHO grade III, and in case of incomplete resection of WHO grade II ependymoma. Chemotherapy alone is reserved for young children <12 months and for adults with recurrent disease when further surgery and irradiation are no longer feasible. A gross total resection is the mainstay of treatment in spinal ependymomas, and radiotherapy is reserved for incompletely resected tumors. Nine subgroups of ependymal tumors across different anatomical compartments (supratentorial, posterior fossa, spinal) and patient ages have been identified with distinct genetic and epigenetic alterations, and with distinct outcomes. These findings may lead to more precise diagnostic and prognostic assessments, molecular subgroup-adapted therapies, and eventually new recommendations pending validation in prospective studies.

https://www.zora.uzh.ch/id/eprint/153708/1/Ruda_2017.pdf

EANO guidelines for the diagnosis and treatment of ependymal tumors.

Object. The authors performed a retrospective analysis of a consecutive series of craniopharyngiomas and their recurrences, which were managed with surgery alone. Methods. In the past 20 years, 37 consecutive patients with craniopharyngiomas underwent surgery without adjuvant radiotherapy. During that period there was a consistent strategy that surgical management was the first choice of treatment whenever possible. Of these 37 patients, 11 experienced tumor recurrence (29.7%) during the mean follow-up period of 11.1 years. Of these 11 patients, seven experienced recurrence after neuroimaging-confirmed total removal, and four patients experienced recurrence after partial or incomplete removal. In these 11 patients, surgical removal was performed 17 times. Using a proper surgical approach (mainly a basal interhemispheric approach) and meticulous microsurgical techniques, total removal of the recurrent tumor was achieved in nine surgeries (52.9). The mortality and morbidity rates associated with these 17 surgeries were 0% and 9.1%, respectively. In most cases, visual function was preserved or improved and intellectual performance was also preserved. Conclusions. Recurrence of craniopharyngioma can be safely managed by using meticulous contemporary microsurgical techniques without additional radiotherapy. The role of surgery and adjuvant radiotherapy for craniopharyngiomas may vary in the future, depending on innovations in treatment and technology. Nevertheless, surgery can be still a major therapeutic option in the management of recurrent craniopharyngiomas.

https://www.unilim.fr/campus-neurochirurgie/IMG/pdf/recurrence-Minamida.pdf

Surgical management of the recurrence and regrowth of craniopharyngiomas

Brain calcinosis syndrome (BCS) usually is defined as bilateral calcium accumulation in the brain parenchyma, primarily in the basal ganglia. More than 50 reported clinical conditions have been associated with BCS. We reviewed clinical, radiological, and genetic features of heredofamilial BCS accompanying all conditions associated with calcium accumulation in the brain reported in English between 1962 and 2003 in MEDLINE. The location, extent, and degree of calcification in the brain show diversity not only among the various disorders but also among patients sharing the same condition. The pathogenesis of BCS is uncertain. More complicated mechanisms may be involved when brain calcinosis is present but calcium, phosphorus, and parathyroid hormone metabolism abnormalities are absent. We review conditions associated with heredofamilial BCS in which brain calcinosis is nearly uniformly present because such information may be important to the clinician pursuing an investigative strategy.

Heredofamilial Brain Calcinosis Syndrome

Safe and minimally invasive laminoplastic laminotomy using an ultrasonic bone curette for spinal surgery: technical note.

PURPOSE The purpose of this article is to assess, in a 25-year retrospective study, the clinical outcome in children with craniopharyngioma. PATIENT AND METHODS From 1978 to 2002, 12 children younger than 15-year-old underwent treatment with surgery and/or radiotherapy for craniopharyngioma. The clinical course and outcome were reviewed. RESULTS The median age was 7.3 years (range, 3 to 12 years) at the time of initial surgical resection. With a mean follow-up period of 132 months (range, 29 to 255 months), 1 patient died of tumor progression due to malignant transformation at 205 months after the initial surgery and the overall outcome was good in 11 patients. Out of 12 patients 4 presented a recurrence of their tumor, 2 after an apparently gross total removal. Because of tumor recurrence, 2 received conventional radiation therapy and 3 received gamma knife radiosurgery. There was neither operative mortality nor major complication. All patients required hormonal replacement postoperatively. CONCLUSIONS The goal in the treatment of craniopharyngiomas is to achieve total removal without morbidity. Our results compared favorably with the previous reports in the literature. MRI follow-up should be performed even in patients whose primary tumor is resected "completely". Suitable combination of open surgery, conventional radiotherapy and gamma knife radiosurgery may result in optimal functional outcome. Recovery from postoperative pituitary dysfunction can be occasionally expected.

Treatment of craniopharyngiomas in children

Coupling of Central Venous Pressure and Intracranial Pressure in a 6-Year-Old Patient With Fontan Circulation and Intracranial Hemorrhage

The benefit of postoperative chemotherapy for anaplastic ependymoma remains unknown. We report two pediatric patients with refractory anaplastic ependymoma treated with temozolomide (TMZ). We did not detect O(6) -methylguanine-DNA methyltransferase (MGMT) promoter methylation in tumor samples; however, MGMT protein expression was low. With TMZ treatment, one patient had a 7-month complete remission; the other, stable disease for 15 months. Three other patients did not respond to TMZ; two had high and one low MGMT expression, and two showed no MGMT promoter methylation. These findings suggest that TMZ may be effective for pediatric refractory anaplastic ependymoma with low MGMT protein expression.

Hiroaki Shigeta

Papers

Safe and minimally invasive laminoplastic laminotomy using an ultrasonic bone curette for spinal surgery: technical note.

Treatment of craniopharyngiomas in children

Coupling of Central Venous Pressure and Intracranial Pressure in a 6-Year-Old Patient With Fontan Circulation and Intracranial Hemorrhage

Temozolomide Treatment for Pediatric Refractory Anaplastic Ependymoma with Low MGMT Protein Expression.

A Classification of Juxta-dural Ring Aneurysms of Internal Carotid Artery