Gait analysis in children treated by surgery followed by adjuvant therapy for posterior fossa tumors.

Children affected by posterior fossa tumors show signs and symptoms of neurological dysfunction, associated both to cancer itself and to cancer therapies. Abnormal gait and coordination difficulties are frequent presenting features. Radiation therapy represents the main adjuvant treatment for these patients. However it can produce significant neurologic injury, also manifested as gait disturbance months after treatment. We have analyzed temporo-spatial parameters of gait in sixteen children treated for posterior fossa tumors, mainly medulloblastomas. In all children we found a typical gait pattern of cerebellar ataxia. There were no significant differences between data obtained in children affected by severe neurological impairment and those having slight or even hardly recognizable physical signs. Although the number of patients studied is not large enough to allow definitive conclusions and gait analyses were performed after treatment, our results suggest that most children treated for posterior fossa tumors have gait disturbances and in some of them these are subclinical. Standard gait analysis laboratory methods can thus be a valuable tool for the careful assessment and follow-up of these patients.

Efficacy of pegylated lyposomal anthracyclines and of intra-arterial carboplatin and doxorubicin combined with local hyperthermia in a case of malignant endovascular papillary angioendothelioma.

Malignant vascular tumors are exceedingly rare in childhood. Generally, their prognosis is dependent from a microscopically complete surgical resection. We observed the case of a 4-year-old boy affected by malignant endovascular papillary angioendothelioma, a rare vascular tumor of intermediate malignancy, involving all his left leg and partially the pelvis. Its very large size hampered any surgical intervention. However, we could demonstrate high sensitivity of the tumor to lyposomal anthracyclines and the child was eventually cured by the intra-arterial administration of carboplatin and doxorubicin coupled with local hyperthermia. This experience probably represents the first step toward an effective treatment of malignant vascular tumors in infancy.

The role of transventricular neuroendoscopy in the management of craniopharyngiomas: three patient reports and review of the literature.

BACKGROUND: Management of craniopharyngiomas is problematic and often requires multimodal protocols. In the last decade neuroendoscopy has been increasingly used in the management of these lesions. PATIENT REPORTS: We report three cases of craniopharyngiomas in which various endsocopic procedures were performed. In the first case the endoscopic approach alone allowed the gross total removal of an intraventricular craniopharyngioma; in the second case the endoscopic fenestration of a cystic intraventricular craniopharyngioma allowed long-term control of the tumor with no further treatment; in the third case endoscopic fenestration and drainage of the cystic part allowed collapse of the cyst with resolution of mass effect on the visual pathway and control of hydrocephalus. The patient later underwent microsurgical removal of the solid portion of the tumor. CONCLUSIONS: Neuroendoscopy has shown great versatility in the management of intra/paraventricular craniopharyngiomas. It can be used alone to achieve gross total removal or marsupialization of cystic tumors, or, more often, in association with additional therapies, such as microsurgery, radiosurgery or intracavitary drug administration.

Second-line chemotherapy with the association of liposomal daunorubicin, carboplatin and etoposide in children with recurrent malignant brain tumors.

Progressive or recurrent high-grade gliomas are characterized by a very poor prognosis, and the relevance of second-line chemotherapy is still unassessed. Although it has been reported that liposomal anthracyclines and carboplatin show some activity in these patients, their association has never been investigated. We have treated six children with recurrent high-grade glioma after surgery, radiotherapy and chemotherapy, and one child with progressive teratoid/rhabdoid tumor with the combination of liposomal daunorubicin and carboplatin plus etoposide. Five out of seven children showed a major response and the 29 month progression-free survival was 38%. The above regimen was feasible and children showed only little and transient hematological toxicity. In our opinion, these results justify further investigation of the above combination chemotherapy for recurrent or progressive malignant brain tumors in children.

Orbital rhabdomyosarcoma: relationship between DNA ploidy, p53, bcl-2, MDR-1 and Ki67 (MIB1) expression and clinical behavior.

BACKGROUND: As for rhabdomyosarcoma (RMS) of other anatomic regions, the evaluation of traditional clinicopathological parameters does not allow the unequivocal outcome prediction of the single cases of orbital RMS. We investigated the role of DNA ploidy and immunohistochemical expression of p53, bcl-2, MDR-1 and Ki67 (MIB1) in the prognostic evaluation of orbital rhabdomyosarcomas. MATERIALS AND METHODS: The study population consisted of 11 selected cases. Serial sections of each tumor, stained with Feulgen's technique, were analyzed for the DNA content, using the QUANTIMET 500c Leica analyzer, QWINVO200A software. The results were compared with the immunohistochemical expression of p53 (wild plus mutated, W&M and mutated), bcl2, MDR-1 and Ki67 (MIB1), and with follow-up data. RESULTS: The statistical analysis of results showed that the cases of tetraploid and/or multiploid RMS, overexpressing p53 (W&M and mutated) and MDR-1, were characterized by an overall worse prognosis. On the contrary, the tumors with a favourable clinical course showed hyperexpression of MIB1 and absence of mutated p53 expression. Significantly higher MIB1 expression was found in the relapse-free group of tumors, with respect to the RMS with relapse (both in primary tumors and relative relapses, p<0.05). This finding could justify the higher sensibility to pharmacological therapy of RMS of the first group. The group of RMS with a worse prognosis (primary tumors and relapses) showed instead p53 overexpression (W&M and mutated), MDR-1 expression and multiploidy, with high 5cEE values and tetraploid peaks. No significant difference was found concerning the expression of bcl-2 among the two groups of RMS (p>0.05). CONCLUSION: The evaluation of DNA ploidy, p53, MIB1 and MDR-1 expression could be used for subtyping of orbital RMS into two prognostically different subcategories, respectively RMS responder to the therapy, with favourable clinical outcome, and RMS with a worse prognosis, requiring more aggressive therapeutic protocols.

Efficacy of sequential chemotherapy including methotrexate and doxorubicin in an infant with partially resected choroid plexus carcinoma.

This report refers to a 3-month-old male, with a residual choroid plexus carcinoma following partial resection, who was successfully treated with sequential chemotherapy without any postoperative radiation therapy. Along with carboplatin, we also used doxorubicin and methotrexate, hypothesizing that, given the patient's age, the blood-brain barrier should not hamper drug delivery to the tumor. According to this hypothesis, the treatment achieved complete remission of the disease, which lasts 27 months after the diagnosis. This result deserves further studies to assess the possible curative role of chemotherapy in very young patients suffering from choroid plexus carcinoma.

Cytogenetic evaluation of isochromosome 17q in posterior fossa tumors of children and correlation with clinical outcome in medulloblastoma. Detection of a novel chromosomal abnormality.

BACKGROUND: A number of chromosomal abnormalities have been described in the presence of central nervous system tumors; isochromosome 17q, representing a loss of heterozygosity for the short arm of the chromosome 17, is the one most frequently reported in association with medulloblastoma. The purpose of this study was to evaluate the prognostic correlation of this variable, compared with other variables (surgery extent and radiotherapy), with survival. METHODS AND RESULTS: We looked for the presence of i(17q) in 32 children affected by posterior fossa tumors, including 16 medulloblastomas and 2 teratoid/rhabdoid tumors. For our study we used both karyotypic analysis and the fluorescence in situ hybridization (FISH) procedure, both on fresh and on paraffin-embedded tissues. Cytogenetic analysis allowed us to detect a hitherto unreported abnormality in medulloblastoma: ins(1;10)(q31;q23q26). Moreover, 16 of the 32 patients analyzed by FISH were found to be positive for the presence of i(17q): the 2 with teratoid/rhabdoid tumors, 11 of 16 with medulloblastomas, plus 1 with ependymoblastoma and 2 with anaplastic astrocytomas. As far as the outcome of medulloblastoma patients is concerned, we found that 8 out of the 10 children whose tumor had been totally removed had a favorable outcome regardless of the presence of i(17q): 4 were i(17q) positive and 4 i(17q) negative. CONCLUSIONS: Although it was impossible to draw any definitive conclusion about detection of i(17q) in central nervous system tumors in infancy, particularly in the case of medulloblastoma, we suggest that this chromosomal abnormality is not an independent prognostic factor, but may be a marker for uncontrolled cell proliferation.