[Brainlife] Newsletter, Vol.3, Suppl.2

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BRAINLIFE NEWSLETTER

Volume 3, Supplement 2 - 25 September 2004	Volume 3 Archive



Special Issue - Pediatric and Childhood Tumors

1: J Neurosurg. 2004 Sep;101(3):536-40.

Endotracheal tube electrodes to map and monitor activities of the vagus nerve intraoperatively. Technical note.

Mikuni N, Satow T, Taki J, Nishida N, Enatsu R, Hashimoto N.

Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan. mikunin@kuhp.kyoto-u.ac.jp

Difficulty swallowing due to damage of the vagus nerve is one of the most devastating complications of surgery in and around the medulla oblongata; therefore, intraoperative anatomical and functional evaluation of this nerve is crucial. The authors applied endotracheal tube surface electrodes to record electromyography (EMG) activity from vocal cords innervated by the vagus nerve. The vagal nucleus or rootlet was electrically stimulated during surgery and vocalis muscle EMG activities were displayed by auditory and visual signals. This technique was used successfully to identify the vagus motor nerve and evaluate its integrity during surgery. The advantages of this method compared with the use of needle electrodes include safe simple electrode placement and stable recording during surgery. In cases involving a pontine cavernoma pressing the nucleus or a jugular foramen tumor encircling the rootlet, this method would be particularly valuable. Additional studies with a larger number of patients are needed to estimate the significance of this method as a means of functional monitoring to predict clinical function.

PMID: 15352615 [PubMed - indexed for MEDLINE]

2: Cancer Chemother Biol Response Modif. 2003;21:655-81.

Brain tumors.

Pueschel JK, Ashby LS, Shapiro WR.

Barrow Neurological Institute, Department of Neurology, Phoenix, Arizona 85013, USA.

Publication Types:

Review
Review, Tutorial

PMID: 15338768 [PubMed - indexed for MEDLINE]

3: J Neurol Neurosurg Psychiatry. 2004 Sep;75(9):1309-13.

Magnetoencephalography (MEG) predicts focal epileptogenicity in cavernomas.

Stefan H, Scheler G, Hummel C, Walter J, Romstock J, Buchfelder M, Blumcke I.

Department of Neurology, Epilepsy and Neuro-Center, University of Erlangen-Nurnberg, Germany. hermann.stefan@neuro.imed.uni-erlangen.de

OBJECTIVE: The aim of this study was to identify the irritative epileptic zone in patients with cavernomas by means of magnetoencephalography (MEG). METHOD: Among 82 patients operated for epilepsy, whose presurgical evaluation had included MEG, histological assessment of the tissue removed had confirmed cavernomas in eight. These eight patients had epilepsy since 18.6 (SD 12.7) years on average. The monitoring lasted about 2.1 (SD 1.3) hours and a median 20.9 (SD 14.3) spikes per hour were recorded. Spontaneous brain activity was recorded by means of a 74 channel dual unit MEG system (Magnes II, 4-D Neuroimaging) with simultaneous EEG recording (31 scalp electrodes). Spike analysis was performed using different source (moving dipole, current density reconstruction) and head models (spherical shells, BEM). Co-registration of neurophysiological and imaging data (MRI) was based upon anatomical landmarks. RESULTS: In 6/8 patients co-localisation from the cavernoma and epileptic zone was found. In two patients the focus was localised in the parieto-occipital lobe, in three patients in the frontal lobe and in three patients in the temporal lobe. In one case of temporal and one case of frontal lobe focus localisation there was no spatial relationship to the cavernoma. CONCLUSION: In cases of focal seizures due to a single cavernoma, MEG may precisely delineate the epileptogenic tissue bordering the lesion. In patients with multiple cavernomas or dual pathology, MSI may reveal the complexity of the case, and contribute to the decision about further invasive diagnostics and more sophisticated therapeutic measures. MEG is a promising method for prediction of the epileptic zone in cavernoma related epilepsies, and thus it can contribute to decision making about and planning of epilepsy surgery.

Publication Types:

Clinical Trial

PMID: 15314122 [PubMed - indexed for MEDLINE]

4: Toxicol Appl Pharmacol. 2004 Sep 1;199(2):118-31.

Epidemiology of brain tumors in childhood--a review.

Baldwin RT, Preston-Martin S.

Department of Family Medicine, Division of Preventive Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA 90095, USA.

Malignant brain tumors are the leading cause of cancer death among children and the second most common type of pediatric cancer. Despite several decades of epidemiologic investigation, the etiology of childhood brain tumors (CBT) is still largely unknown. A few genetic syndromes and ionizing radiation are established risk factors. Many environmental exposures and infectious agents have been suspected of playing a role in the development of CBT. This review, based on a search of the medical literature through August 2003, summarizes the epidemiologic evidence to date. The types of exposures discussed include ionizing radiation, N-nitroso compounds (NOC), pesticides, tobacco smoke, electromagnetic frequencies (EMF), infectious agents, medications, and parental occupational exposures. We have chosen to focus on perinatal exposures and review some of the recent evidence indicating that such exposures may play a significant role in the causation of CBT. The scientific community is rapidly learning more about the molecular mechanisms by which carcinogenesis occurs and how the brain develops. We believe that advances in genetic and molecular biologic technology, including improved histologic subtyping of tumors, will be of huge importance in the future of epidemiologic research and will lead to a more comprehensive understanding of CBT etiology. We discuss some of the early findings using these technologies.

Publication Types:

Review
Review, Academic

PMID: 15313584 [PubMed - indexed for MEDLINE]

5: Pediatr Nurs. 2004 May-Jun;30(3):238-41.

The story of Margaret and her family: forced choices, obligations, and hope.

Carnevale FA.

McGill University, Montreal, Quebec, Canada.

Publication Types:

Case Reports

PMID: 15311651 [PubMed - indexed for MEDLINE]

6: J Clin Oncol. 2004 Aug 15;22(16):3357-65.

Results of a phase II upfront window of pharmacokinetically guided topotecan in high-risk medulloblastoma and supratentorial primitive neuroectodermal tumor.

Stewart CF, Iacono LC, Chintagumpala M, Kellie SJ, Ashley D, Zamboni WC, Kirstein MN, Fouladi M, Seele LG, Wallace D, Houghton PJ, Gajjar A.

Department of Pharmaceutical Sciences, St Jude Children's Research Hospital, 332 N Lauderdale, Memphis, TN 38105-2794, USA.

PURPOSE: To assess the antitumor efficacy of pharmacokinetically guided topotecan dosing in previously untreated patients with medulloblastoma and supratentorial primitive neuroectodermal tumors, and to evaluate plasma and CSF disposition of topotecan in these patients. PATIENTS AND METHODS: After maximal surgical resection, 44 children with previously untreated high-risk medulloblastoma were enrolled, of which 36 were assessable for response. The topotecan window consisted of two cycles, administered initially as a 30-minute infusion daily for 5 days, lasting 6 weeks. Pharmacokinetic studies were conducted on day 1 to attain a topotecan lactone area under the plasma concentration-time curve (AUC) of 120 to 160 ng/mL.h. After 10 patients were enrolled, the infusion was modified to 4 hours, with dosage individualization. RESULTS: Of 36 assessable patients, four patients (11.1%) had a complete response and six (16.6%) showed a partial response, and disease was stable in 17 patients (47.2%). Toxicity was mostly hematologic, with only one patient experiencing treatment delay. The target plasma AUC was achieved in 24 of 32 studies (75%) in the 30-minute infusion group, and in 58 of 93 studies (62%) in the 4-hour infusion group. The desired CSF topotecan exposure was achieved in seven of eight pharmacokinetic studies when the topotecan plasma AUC was within target range. CONCLUSION: Topotecan is an effective agent against pediatric medulloblastoma in patients who have received no therapy other than surgery. Pharmacokinetically guided dosing achieved the target plasma AUC in the majority of patients. This drug warrants testing as part of standard postradiation chemotherapeutic regimens. Furthermore, these results emphasize the importance of translational research in drug development, which in this case identified an effective drug.

Publication Types:

Clinical Trial
Clinical Trial, Phase II

PMID: 15310781 [PubMed - indexed for MEDLINE]

7: J Neurosurg. 2004 Aug;101(2):227-32.

Endoscope-assisted microsurgical resection of epidermoid tumors of the cerebellopontine angle.

Schroeder HW, Oertel J, Gaab MR.

Department of Neurosurgery, Ernst Moritz Arndt University, Greifswald, Germany. henry.schroeder@uni-greifswald.de

OBJECT: Epidermoid tumors located in the cerebellopontine angle (CPA) are challenging lesions because they grow along the subarachnoid spaces around delicate neurovascular structures and often extend into the middle cranial fossa. The purpose of this study was to determine the value of endoscopic assistance in the microsurgical resection of these lesions, in which total removal is the therapy of choice. METHODS: Eight patients harboring an epidermoid tumor of the CPA were treated using an endoscope-assisted microsurgical technique. A retrosigmoid suboccipital approach was used in five patients and a pterional transsylvian approach was chosen in the other three. In four patients the lesion was resected microsurgically and the endoscope was used repeatedly to verify complete tumor removal, whereas most of the tumor mass was removed with the aid of an operating microscope in the other four. Tumor parts extending into other cranial compartments that were not visible through the microscope were removed under endoscopic view by using rigid rod-lens scopes with 30 and 70 degrees angles of view. All epidermoids were completely evacuated and the membranes were widely resected. Large tumors occupying both the middle and posterior cranial fossa were removed through a single small opening without enlarging the craniotomy. Permanent hearing loss and permanent hypacusis were observed in one patient each. One patient with facial and one with abducent nerve palsy recovered within 6 and 4 months, respectively. A transient weakness of the chewing muscles was encountered in one patient. Postoperative magnetic resonance imaging revealed no residual tumor in any patient. To date no recurrences have been-observed (follow up range 12-98 months). CONCLUSIONS: The endoscope-assisted microsurgical technique enables safe removal even when tumor parts are not visible in a straight line. Tumor extensions into adjacent cranial compartments can be removed with the same approach without retracting neurovascular structures or enlarging the craniotomy.

Publication Types:

Case Reports

PMID: 15309912 [PubMed - indexed for MEDLINE]

8: Cancer. 2004 Aug 15;101(4):817-24.: Near complete surgical resection predicts a favorable outcome in pediatric patients with nonbrainstem, malignant gliomas: results from a single center in the magnetic resonance imaging era.

Bucci MK, Maity A, Janss AJ, Belasco JB, Fisher MJ, Tochner ZA, Rorke L, Sutton LN, Phillips PC, Shu HK.

Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.

BACKGROUND: Because few reports on outcome in patients with pediatric malignant gliomas during the magnetic resonance imaging era were available, the authors studied the outcomes of children with these tumors at their institution. METHODS: The medical records of 39 patients with nonbrainstem, malignant gliomas who were treated at the Hospital of the University of Pennsylvania/Children's Hospital of Philadelphia between February 1, 1989 and December 31, 2000 were reviewed retrospectively. Magnetic resonance imaging was used to assess tumors at presentation and at follow-up. Progression-free survival (PFS) and overall survival (OS) were determined using the Kaplan-Meier method. Univariate and multivariate analyses were performed using a Cox proportional hazards model. RESULTS: The median follow-up for the 14 surviving patients was 47.6 months. The median PFS for all patients was 12.2 months, and the median OS for all patients was 21.3 months. The extent of surgery was the strongest prognostic factor for predicting outcomes in these patients, with a median survival of 122.2 months in patients who underwent macroscopic total resection compared with 14.1 months in patients who had significant residual disease after surgery. In univariate analyses, other than the extent of surgery, only the absence of visual symptoms at diagnosis significantly predicted improved OS. Local control was improved for patients who underwent better resection and had smaller tumors. In multivariate analyses, although the extent of surgery continued to predict outcomes significantly, histologic grade, which was not significant in the univariate analysis, also was significant. CONCLUSIONS: Children with malignant gliomas appeared to fare better than their adult counterparts. Because the extent of resection was one of the strongest predictors of outcome, the authors concluded that the optimal therapy for these patients would include the maximal possible resection. Copyright 2004 American Cancer Society.

PMID: 15305415 [PubMed - indexed for MEDLINE]

9: J Clin Endocrinol Metab. 2004 Aug;89(8):3776-84.: Multiple endocrine neoplasia type 1 variant with frequent prolactinoma and rare gastrinoma.

Hao W, Skarulis MC, Simonds WF, Weinstein LS, Agarwal SK, Mateo C, James-Newton L, Hobbs GR, Gibril F, Jensen RT, Marx SJ.

Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.

No variant of multiple endocrine neoplasia type 1 (MEN1) has been reproducible among families. We examined two large kindreds with MEN1 variants, and we compared these to past reports. The two kindreds were followed up for 20-30 yr with MEN1 tumors in 30 members.Results in cases from two kindreds were that 93% showed parathyroid adenoma, 40% pituitary tumor (always prolactinoma), and 27% enteropancreatic endocrine tumor. The latter included 10% insulinoma, 7% nonfunctioning islet tumor, but only 10% gastrinoma. Compared with prior large series, this lower prevalence of gastrinoma (10% vs. 42%, P < 0.01) and higher prevalence of prolactinoma (40% vs. 22%, P < 0.01) define this variant. Many possible biases of retrospective analyses were excluded as possible explanations. Previously sequenced DNA showed no characteristic MEN1 mutation in these two kindreds and in a third, reported previously; the lack of any shared MEN1 mutation also excluded common ancestry for MEN1 among the three kindreds. The causes for differences between this variant and typical MEN1 are unknown.In conclusion, this variant shows more frequent prolactinoma and less frequent gastrinoma than typical MEN1; the variant is reproducible among kindreds. MEN1 carriers in such families should have periodic monitoring adjusted for the expected penetrance of tumors.

PMID: 15292304 [PubMed - indexed for MEDLINE]

http://jcem.endojournals.org/cgi/reprint/89/8/3776

10: J Neurosurg Spine. 2004 May;100(5):525-9.

Juvenile pilocytic astrocytoma presenting with subarachnoid hemorrhage. Case report and review of the literature.

Garg A, Chugh M, Gaikwad SB, Chandra SP, Gupta V, Mishra NK, Sharma MC.

Department of Neuroradiology, All India Institute of Medical Sciences, New Delhi, India. ajay@desmat.com

The authors report a case of a 13-year-old boy with juvenile pilocytic astrocytoma (JPA) presenting with subarachnoid hemorrhage (SAH). The patient experienced sudden onset of headache, vomiting, and loss of consciousness. Cranial computerized tomography scanning revealed blood within basal cisterns and the third ventricle. Angiography demonstrated normal cerebral vasculature and upward displacement of the bilateral A, segments of the anterior cerebral artery. Magnetic resonance (MR) imaging revealed a chiasmatic/hypothalamic mass with evidence of hemorrhage. The mass was surgically decompressed. Histopathological examination showed evidence of JPA. In all cases of SAH in which there is blood around the third ventricle and a raised A1 segment on angiography, MR imaging should be performed. The presence of a normal sella turcica, as well as indistinct margins between the tumor and the opticochiasmatic apparatus should raise suspicion about the lesion.

Publication Types:

Case Reports
Review
Review of Reported Cases

PMID: 15287467 [PubMed - indexed for MEDLINE]

11: J Neurosurg Spine. 2004 May;100(5):437-41.

Initial endoscopic management of pineal region tumors and associated hydrocephalus: clinical series and literature review.

Yamini B, Refai D, Rubin CM, Frim DM.

Sections of Pediatric Neurosurgery and Pediatric Hematology-Oncology, University of Chicago Children's Hospital, University of Chicago, Illinois 60637, USA. byamini@surgery.bsd.uchicago.edu

OBJECT: The authors report their experience in six patients with pineal tumors and associated hydrocephalus who underwent an endoscopic biopsy procedure and third ventriculocisternostomy (ETVC) in a single sitting. METHODS: The ETVC was successfully performed without complication in all patients; however, a ventriculoperitoneal shunt was eventually required in four. Histological diagnosis was successfully established in four patients. The authors also reviewed the literature to assess reports involving ETVC and tumor biopsy sampling in patients with pineal tumors and hydrocephalus. A total of 54 cases, including those in this study, have been reported. Fifteen percent of the patients eventually required placement of a ventricular shunt. The transient complication rate was 15% with no death. A positive tissue diagnosis was established in 89% of the cases overall. CONCLUSIONS: The authors conclude that the endoscopic management of patients with pineal region masses and hydrocephalus may be a preferred initial strategy.

Publication Types:

Case Reports
Review
Review of Reported Cases

PMID: 15287451 [PubMed - indexed for MEDLINE]

12: J Clin Oncol. 2004 Aug 1;22(15):3156-62.

Preliminary results from a phase II trial of conformal radiation therapy and evaluation of radiation-related CNS effects for pediatric patients with localized ependymoma.

Merchant TE, Mulhern RK, Krasin MJ, Kun LE, Williams T, Li C, Xiong X, Khan RB, Lustig RH, Boop FA, Sanford RA.

Department of Biostatistics, St Jude Children's Research Hospital, 332 N Lauderdale St, Memphis, TN 38105-2794, USA. thomas.merchant@stjude.org

PURPOSE: We conducted a phase II trial of conformal radiation therapy (CRT) for localized childhood ependymoma to determine whether the irradiated volume could be reduced to decrease CNS-related side effects without diminishing the rate of disease control. PATIENTS AND METHODS: Between July 1997 and January 2003, 88 pediatric patients (median age, 2.85 +/- 4.5 years) received CRT in which doses (59.4 Gy to 73 patients or 54.0 Gy after gross-total resection to 15 patients younger than 18 months) were administered to the gross tumor volume and a margin of 10 mm. Patients were categorized according to extent of resection (underwent gross total resection, n = 74; near-total resection, n = 6; subtotal resection, n = 8), prior chemotherapy (n = 16), tumor grade (anaplastic, n = 35), and tumor location (infratentorial, n = 68). An age-appropriate neurocognitive battery was administered before and serially after CRT. RESULTS: The median length of follow-up was 38.2 months (+/- 16.4 months); the 3-year progression-free survival estimate was 74.7% +/- 5.7%. Local failure occurred in eight patients, distant failure in eight patients, and both in four patients. The cumulative incidence of local failure as a component of failure at 3 years was 14.8% +/- 4.0%. Mean scores on all neurocognitive outcomes were stable and within normal limits, with more than half the cohort tested at or beyond 24 months. CONCLUSION: Limited-volume irradiation achieves high rates of disease control in pediatric patients with ependymoma and results in stable neurocognitive outcomes. Copyright 2004 American Society of Clinical Onocology

Publication Types:

Clinical Trial
Clinical Trial, Phase II

PMID: 15284268 [PubMed - indexed for MEDLINE]

13: Neuro-oncol. 2004 Jul;6(3):236-46.

Results of a phase 1 study utilizing monocyte-derived dendritic cells pulsed with tumor RNA in children and young adults with brain cancer.

Caruso DA, Orme LM, Neale AM, Radcliff FJ, Amor GM, Maixner W, Downie P, Hassall TE, Tang ML, Ashley DM.

Department of Hematology and Oncology, The Royal Children's Hospital, Parkville, Victoria, 3051, Australia.

We conducted a phase 1 study of 9 pediatric patients with recurrent brain tumors using monocyte-derived dendritic cells pulsed with tumor RNA to produce antitumor vaccine (DCRNA) preparations. The objectives of this study included (1) establishing safety and feasibility and (2) measuring changes in general, antigen-specific, and tumor-specific immune responses after DCRNA. Dendritic cells were derived from freshly isolated monocytes after 7 days of culture with IL-4 and granulocyte-macrophage colony-stimulating factor, pulsed with autologous tumor RNA, and then cryopreserved. Patients received at least 3 vaccines, each consisting of an intravenous and an intradermal administration at biweekly intervals. The study showed that this method for producing and administering DCRNA from a single leukapheresis product was both feasible and safe in this pediatric brain tumor population. Immune function at the time of enrollment into the study was impaired in all patients tested. While humoral responses to recall antigens (diphtheria and tetanus) were intact in all patients, cellular responses to mitogen and recall antigens were below normal. Following DCRNA vaccine, 2 of 7 patients showed stable clinical disease and 1 of 7 showed a partial response. Two of 7 patients who were tested showed a tumor-specific immune response to DCRNA. This study showed that DCRNA vaccines are both safe and feasible in children with tumors of the central nervous system with a single leukapheresis.

Publication Types:

Clinical Trial
Clinical Trial, Phase I

PMID: 15279716 [PubMed - indexed for MEDLINE]

14: Ann Otol Rhinol Laryngol. 2004 Jul;113(7):533-43.

Primitive neuroectodermal tumor of the head and neck: incidence, diagnosis, and management.

Windfuhr JP.

Department of Otorhinolaryngology-Plastic Head and Neck Surgery, St Anna Hospital, Duisburg, Germany.

Primitive neuroectodermal tumors are in the Ewing's sarcoma family of tumors and are composed of small round cells. Because of their rare occurrence, optimal therapy is challenging, particularly if they occur in the head and neck. Diagnosis is based on history, immunostaining with at least 2 neural markers, ultrastructural examination, and evidence of an abnormal t(11;22)(q24;q12) translocation as the hallmark for the Ewing's sarcoma family. The prognosis in general is poor because of overt metastasis at the time of diagnosis. Of 27 reported patients with primitive neuroectodermal tumors of the head and neck, 23 were less than 20 years of age. Most patients presented with a tumor in the nasal cavity, paranasal sinuses, or neck. Symptoms developed rapidly (3.6 months, on average), and a lethal outcome occurred in 9 patients. This highly malignant tumor requires an aggressive combination of radical resection, chemotherapy, and radiotherapy. A close follow-up with regular radiographic examination for at least 5 years is mandatory.

Publication Types:

Case Reports
Review
Review of Reported Cases

PMID: 15274413 [PubMed - indexed for MEDLINE]

15: Cancer. 2004 Aug 1;101(3):620-6.: Brain metastases of malignant germ cell tumors in children and adolescents.

Spunt SL, Walsh MF, Krasin MJ, Helton KJ, Billups CA, Cain AM, Pappo AS.

Department of Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. sheri.spunt@stjude.org

BACKGROUND: Brain metastases of pediatric germ cell tumors are uncommon, and there is limited information regarding their incidence, clinical presentation, response to treatment, and influence on survival. METHODS: The authors reviewed the experience with brain metastases from pediatric germ cell tumors at St. Jude Children's Research Hospital (Memphis, TN) over a 40-year period. RESULTS: Between March 1962 and February 2002, 16 of 206 patients with germ cell tumors (7.8%) had brain metastases at the time of initial presentation (n = 2), later in the course of the illness (n = 12), or at autopsy (n = 2). Twelve of 16 patients (75%) had symptoms referable to the brain (nausea/emesis, headaches, or seizures), and 14 (88%) had pulmonary metastases at the time brain metastases were identified. Patients with brain metastases were more likely to have an extragonadal primary tumor (P = 0.013), advanced-stage disease at initial presentation (P = 0.016), and choriocarcinoma within the primary tumor (P < 0.001). The incidence of brain metastases was significantly lower in the second 2 decades of the study period (5 of 135 patients [3.7%]) than in the first 2 decades (11 of 71 patients [15.5%]; P = 0.005). Two of the 16 patients in the current study are long-term survivors. CONCLUSIONS: Brain metastases are uncommon in childhood germ cell tumors, and their incidence appears to be decreasing. In the current study, most patients with such metastases were symptomatic and had pulmonary metastases at the time brain metastases were identified. Patients with the highest risk of developing brain metastases include those with extragonadal tumors, those with high disease stage at initial presentation, and those with choriocarcinoma as a component of the primary tumor. The probability of survival is poor, although a small proportion of patients may become long-term survivors.

PMID: 15274076 [PubMed - indexed for MEDLINE]

16: Arch Dis Child. 2004 Aug;89(8):792.: Paediatric craniopharyngioma.

Williams T.

h.marcovitch@btinternet.com

PMID: 15269087 [PubMed - indexed for MEDLINE]

17: AJR Am J Roentgenol. 2004 Aug;183(2):505-11.: Trilateral retinoblastoma: clinical and radiologic progression.

Provenzale JM, Gururangan S, Klintworth G.

Department of Radiology, Duke University Medical Center, Box 3808, Durham, NC 27710, USA.

OBJECTIVE: The purpose of this study was to assess the clinical and radiologic features of tumor progression in children with trilateral retinoblastoma. MATERIALS AND METHODS: Clinical records of eight children with trilateral retinoblastoma were reviewed for the patient's age at the time of diagnosis of the ocular tumor, time interval from diagnosis of ocular retinoblastoma to discovery of the intracranial tumor, time interval from diagnosis of retinoblastoma to death, and time interval from diagnosis of the intracranial tumor to death. CT or MRI studies were reviewed for the appearance of the primary intracranial neoplasm, intracranial metastases, and spinal metastases. RESULTS: The mean age of the patients at diagnosis of bilateral retinoblastoma was 4.5 months, and the mean age at diagnosis of the intracranial midline tumor was 26 months. The mean interval from the time of diagnosis of retinoblastoma to discovery of the intracranial tumor was 21.5 months. Two children had spinal leptomeningeal metastases at the time of discovery of the midline intracranial mass although no intracranial metastases were seen on imaging. In the other children, intracranial and spinal leptomeningeal metastases frequently developed within months of the diagnosis of retinoblastoma despite lack of progression in the midline intracranial lesion. Six children died of leptomeningeal spread of tumor. The mean interval from diagnosis of the ocular tumor to death was 46 months and from diagnosis of the intracranial tumor to death was 17 months. One child developed metastatic retinoblastoma in the ulna 10 years after the diagnosis of the intracranial tumor. CONCLUSION: Children typically died of leptomeningeal tumor dissemination despite lack of progression in the midline intracranial mass. Effective treatment of trilateral retinoblastoma may require close evaluation of these children for leptomeningeal dissemination.

PMID: 15269048 [PubMed - indexed for MEDLINE]

18: Br J Cancer. 2004 Aug 2;91(3):425-9.

Temozolomide in paediatric high-grade glioma: a key for combination therapy?

Verschuur AC, Grill J, Lelouch-Tubiana A, Couanet D, Kalifa C, Vassal G.

Department of Paediatric Oncology, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, France. a.c.verschuur@amc.uva.nl

This report describes a single-centre study with temozolomide (TMZ) (200 mg m(-2) day(-1) x 5 per cycle of 28 days) in children with (recurrent) high-grade glioma. Magnetic resonance imaging was performed every two cycles. In all, 20 patients were treated between 1998 and 2001 after the UKCCSG/SFOP TMZ phase II trial. All patients had measurable disease. Totally, 15 patients had a relapse after surgery+/-radiotherapy+/-chemotherapy. Overall, five patients received TMZ after surgery or biopsy, awaiting radiotherapy. There were one clinically malignant grade II glioma, 11 grade III and eight grade IV gliomas. Seven tumours had oligodendroglial features. Mean age at start of TMZ was 12.0 years (range 3-20.5 years). In total, eight patients had >8 cycles (range 3-30). One VGPR (currently in CR after surgery), three PRs (with a PFS of 4, 4 and 11 months, respectively) and one MR (PFS 14 months) were observed. Three out of five responses occurred after >4 courses. The overall response rate was 20%. Median progression-free survival (PFS) was 2.0 months (range 3 weeks-34+ months). PFS rate was 20% after 6 months. Median overall survival (OS) was 10 months. Nine patients showed a clinical improvement. Three patients vomitted shortly after TMZ administration, eight patients (13 cycles) experienced grade III/IV thrombocytopenia, occurring predominantly during the fourth week of the first two cycles. Five patients experienced neutropenia, and three patients febrile neutropenia. TMZ is a well-tolerated ambulatory treatment for children with malignant glial tumours. This drug warrants further study in these highly chemoresistant tumours and should be studied either as upfront therapy or in combination therapy.

Publication Types:

Clinical Trial

PMID: 15266331 [PubMed - indexed for MEDLINE]

19: Neuropsychol Rev. 2004 Mar;14(1):65-86.

A critical review of the clinical effects of therapeutic irradiation damage to the brain: the roots of controversy.

Armstrong CL, Gyato K, Awadalla AW, Lustig R, Tochner ZA.

Department of Neurology, University of Pennsylvania Medical School, Philadelphia, Pennsylvania 19104, USA. armstrongc@email.cho.edu

We critically examined the damaging affects of therapeutic irradiation by comparing results from cross-disciplinary studies of early- and late-delayed radiotherapy effects. Focus is attained by concentrating on clinical treatment issues (volume of brain, dose, timing of effects, age, modality types, and stereotactic treatment techniques), rather than on methodological means or problems, which is necessary to understand the mechanisms and characteristics of radiotherapy-induced behavioral dysfunction including cognition. We make observations and hypotheses about the actual risks from radiotherapy that could be informative in the treatment decision process, and which may lessen the concerns of some patients and their families about the risks they take when receiving radiation. Conditions that predispose to radiation injury are reviewed: (1) higher doses even to part of the brain versus lower doses to the whole brain, (2) combined treatment modalities, (3) malignancy itself, (4) radiation early during postnatal brain development, and (5) late-delayed effects (more than 3 years posttreatment). Current neurocognitive frameworks for understanding cognitive change over time in children and adults are summarized, along with the literature on effects of brain tumors and treatment on depression. No studies have as yet identified candidate brain regions that are more sensitive to radiotherapy. Two studies have provided early, preliminary evidence for a specific vulnerability of visual attention/memory to the early stage of late radiation damage. Furthermore, radiation effects appear severe only in a minority of patients. Risk is related to direct and indirect effects of cancer type, concurrent clinical factors, and premorbid risk factors.

Publication Types:

Review
Review, Academic

PMID: 15260139 [PubMed - indexed for MEDLINE]

20: Onkologie. 2004 Jun;27(3):239-45.

High-dose chemotherapy in childhood brain tumors.

Wolff JE, Finlay JL.

Abteilung Padiatrische Hamatologie und Onkologie, Krankenhaus Barmherzige Bruder, Klinik St. Hedwig, Regensburg, Germany. johannes.wolff@barmherzige-regensburg.de

Early attempts to use high-dose chemotherapy technology in order to improve the effect of nitrosourea on high-grade gliomas resulted in minimal benefit as well as in severe toxicity. Since then, other drugs have been applied in conjunction with either autologous bone marrow or peripheral blood stem cells, including thiotepa, etoposide, melphalan, cyclophosphamide, and busulfan. The data suggest benefit in recurrent primitive neuroectodermal tumors (PNET), in newly diagnosed young children with PNET and possibly in young children with newly diagnosed ependymoma, as a strategy not only to improve tumor-free survival but also to avoid exposure of the young brain to irradiation. In other tumors such as recurrent ependymoma and newly diagnosed or recurrent brain stem glioma, high-dose chemotherapy remains ineffective. New protocols under evaluation include new agents, multiple cycles of high-dose chemotherapy and allogeneic transplantation as immunotherapeutic approach. Copyright 2004 S. Karger GmbH, Freiburg

Publication Types:

Review
Review, Tutorial

PMID: 15249712 [PubMed - indexed for MEDLINE]

21: J Clin Endocrinol Metab. 2004 Jul;89(7):3371-6.: Pituitary magnetic resonance imaging findings do not influence surgical outcome in adrenocorticotropin-secreting microadenomas.

Salenave S, Gatta B, Pecheur S, San-Galli F, Visot A, Lasjaunias P, Roger P, Berge J, Young J, Tabarin A, Chanson P.

Department of Endocrinology and Reproductive Diseases, Assistance Publique-Hopitaux de Paris, Centre Hospitalier d'Universite Bicetre, 78 rue du General Leclerc, F-94275 Le Kremlin-Bicetre, France.

The pituitary origin of ACTH secretion in ACTH-dependent hypercortisolism can be difficult to assess, as magnetic resonance imaging (MRI) frequently fails to identify ACTH-secreting microadenomas or, on the contrary, may give false positive images of microadenomas. The choice of therapeutic option for patients with such normal MRI findings is controversial. Some groups propose routinely pituitary surgery, whereas others consider that neurosurgical exploration may be less successful and more harmful, and therefore prefer other types of management. The aim of this study was to compare surgical outcomes between patients with Cushing's disease (CD) and normal vs. positive pituitary MRI findings. Fifty-four patients (44 women and 10 men) with CD, operated on after 1996 in two centers (Kremlin-Bicetre and Bordeaux) and followed postoperatively during a mean period of 19.9 +/- 22.7 months (range, 1-89 months), were enrolled in this retrospective study. Twenty-eight patients had normal pituitary MRI findings, and the pituitary origin of ACTH was established by bilateral petrosal sinus sampling in all of these cases. Twenty-six patients had positive MRI findings clearly showing a microadenoma. The two groups were not significantly different in terms of the sex ratio, age, frequency of hypertension, or diabetes, basal 24-h urinary free cortisol levels and follow-up. All of the patients were operated on by two experienced neurosurgeons using the same surgical protocol. Selective adenomectomy was performed when a tumor was identified, and subtotal hypophysectomy was performed when the lesion was uncertain or when no tumor was found during surgical exploration. Respectively, 50% and 84% of patients with normal and positive MRI results underwent adenomectomy (P < 0.05). A pituitary adenoma (confirmed by pathological examination) was found at surgery in 53% and 88% of patients in the normal and positive MRI groups, respectively (P < 0.05). The early surgical success rate (combining patients with corticotropic deficiency and patients with eucortisolism) was similar in the normal and positive MRI groups (78% and 88%, respectively; P = 0.85). The recurrence rate was lower in the normal MRI group, but the difference did not reach statistical significance (9% vs. 30%; P = 0.07). The final remission rate at the last visit was similar in the normal and positive MRI groups (72% and 61%, respectively; P = 0.29). Postoperative complications were also similar: 10 patients (36%) with normal MRI and five patients (20%) with positive MRI had at least one postoperative complication (surgical and/or pituitary deficiency; P = 0.12). Thus, the outcome of pituitary surgery in CD appears to be similar regardless of whether pituitary MRI shows a microadenoma. We recommend neurosurgical pituitary exploration as the first-line treatment of CD, provided that the pituitary origin of ACTH secretion is confirmed by bilateral petrosal sinus sampling in patients with normal pituitary MRI findings.

PMID: 15240617 [PubMed - indexed for MEDLINE]

http://jcem.endojournals.org/cgi/reprint/89/7/3371

22: J Clin Endocrinol Metab. 2004 Jul;89(7):3298-305.: Longitudinal study on growth and body mass index before and after diagnosis of childhood craniopharyngioma.

Muller HL, Emser A, Faldum A, Bruhnken G, Etavard-Gorris N, Gebhardt U, Oeverink R, Kolb R, Sorensen N.

Department of Pediatrics, Zentrum fur Kinder- und Jugendmedizin, Klinikum Oldenburg GmbH, Dr. Eden Strasse 10, 26133 Oldenburg, Germany. mueller.hermann@klinikum-oldenburg.de

We analyzed whether childhood craniopharyngioma predisposes to obesity and growth impairment. Height/length, body mass index (BMI), and hypothalamic involvement were evaluated in 90 patients at standardized ages and time points before, after, and at the time of diagnosis. Relevant decreases in height sd score (SDS) started at 10-12 months of age and persisted until diagnosis of childhood craniopharyngioma. Relevant increases in BMI SDS were detectable between 4 and 5 yr of age. Postoperative BMI SDS (yr 1-6) had a weak positive correlation with BMI SDS at the time of diagnosis. In linear regression analysis, hypothalamic tumor involvement (P < 0.001), ponderal index at birth (P = 0.014), and BMI SDS at age 6-7 months (P = 0.029) and at age 5 yr (P < 0.001) had relevant and independent impacts on the development of obesity. Patients with hypothalamic involvement (n = 48) presented lower ponderal index and BMI SDS at birth and higher BMI SDS at the time of diagnosis (P < 0.001) as well as during annual follow-up (P < 0.001) compared with patients without hypothalamic involvement (n = 42). From childhood (3.5-4 yr) to the time of diagnosis, growth rates were reduced for patients with hypothalamic tumor involvement. Patients without hypothalamic involvement presented reduced growth rates in early infancy (age 10-12 months) that persisted until diagnosis. We conclude that reduced growth rates occur quite early in history; BMI SDS increases occur later and are predictive of obesity. Hypothalamic involvement is the major risk factor for obesity in patients with childhood craniopharyngioma.

PMID: 15240606 [PubMed - indexed for MEDLINE]

http://jcem.endojournals.org/cgi/reprint/89/7/3298

23: Acta Radiol. 2004 May;45(3):344-7.

Primary intracranial myxopapillary ependymomas: report of two cases and review of the literature.

Tseng YC, Hsu HL, Jung SM, Chen CJ.

2nd Department of Diagnostic Radiology, Chang Gung Memorial Hospital and University, Taipei, Taiwan, ROC.

Myxopapillary ependymoma is a variant of ependymoma occurring almost exclusively in the conus medullaris or filum terminale. Myxopapillary ependymoma found primarily in the brain is extremely rare. Two such cases appearing at the 4th ventricle and cerebral falx are reported. The imaging features of such tumors are a primary cystic mass with strong enhancement at its solid part. Myxopapillary ependymoma should be a possible differential diagnosis when an intracranial cystic tumor is found.

Publication Types:

Case Reports
Review
Review, Tutorial

PMID: 15239433 [PubMed - indexed for MEDLINE]

24: Pediatr Blood Cancer. 2004 Aug;43(2):126-33.

Intensive cisplatin and cyclophosphamide-based chemotherapy without radiotherapy for intracranial germinomas: failure of a primary chemotherapy approach.

Kellie SJ, Boyce H, Dunkel IJ, Diez B, Rosenblum M, Brualdi L, Finlay JL.

Oncology Unit, The Children's Hospital at Westmead, Sydney, NSW, Australia. stewartk@chw.edu.au

PURPOSE: High rates of overall and event-free survival have been reported in patients with intracranial germinomas treated with craniospinal radiotherapy. More recently, similar results have been reported with chemotherapy combined with radiotherapy to more localized treatment volumes. Our interest in exploring chemotherapy without radiotherapy in patients with CNS germinomas was based on concerns about the late sequelae of radiotherapy to the brain or neuraxis and also the well documented success of chemotherapy alone in patients with disseminated extracranial germinomas. The primary objective of this study was to determine whether intensive cisplatin and cyclophosphamide-based combination chemotherapy, without radiotherapy, was effective in patients with CNS germinomas. PATIENTS AND METHODS: Nineteen patients were enrolled, ranging in age from 1 to 24 years (median, 14 years). Thirteen were male. Nine had diabetes insipidus. Therapy comprised two courses of Regimen 'A' (cisplatin, etoposide, cyclophosphamide, and bleomycin) followed by MRI evaluation. Patients achieving a complete remission (CR) completed all planned therapy with two courses of regimen 'B' (carboplatin, etoposide, and bleomycin). Patients achieving less than a CR received two courses of Regimen 'B' followed by another evaluation. Those in CR after four courses of treatment received one additional course of Regimen 'A' and Regimen 'B', while those not in CR after four treatment courses underwent second look surgery and/or radiation therapy. RESULTS: Eleven of 11 patients with residual postoperative disease assessable for response achieved a CR. With a median follow-up of 6.5 years, eight out of 19 (0.42) patients remain in CR 1 without radiotherapy and another three patients are in stable second or subsequent remissions. Three patients died from treatment-related toxicity and another died in CR 1 from an uncharacterized leukoencephalopathy. The 5-year event-free survival (EFS) was 0.47 +/- 0.23 and 5-year overall survival (OS) was 0.68 +/- 0.22. CONCLUSIONS: Intensive cisplatin and cyclophosphamide-based chemotherapy was effective in achieving remissions, however, the long-term outcome using this treatment program was unsatisfactory and associated with unacceptable morbidity and mortality, particularly in patients with diabetes insipidus. Copyright 2004 Wiley-Liss, Inc.

Publication Types:

Clinical Trial

PMID: 15236278 [PubMed - indexed for MEDLINE]

25: Kaohsiung J Med Sci. 2004 May;20(5):240-6.

Extraskeletal intracranial mesenchymal chondrosarcoma: case report and literature review.

Chen JY, Hsu SS, Ho JT.

Division of Neurosurgery, Department of Surgery, Veterans General Hospital-Kaohsiung, Kaohsiung, Taiwan.

We present the case of a 13-year-old girl with a huge intracranial mesenchymal chondrosarcoma. She had suffered from severe headache, diplopia, intermittent nausea and vomiting for 1 month. Neurologic examination revealed bilateral blurred optic disc margins and abducens paresis. Magnetic resonance imaging demonstrated a giant, heterogeneous, intensely enhancing mass of 7 x 8 x 6 cm, occupying the bilateral frontal and left high parietal regions and based on the anterior cerebral falx. A presumptive diagnosis of aggressive meningioma was made. The patient underwent bicoronal craniotomy and gross total resection of the tumor. Pathologic examination revealed an extraskeletal mesenchymal chondrosarcoma. She was under regular follow-up and remained free of recurrence after surgery. In addition to the current case, we review previously reported cases of extraskeletal intracranial mesenchymal chondrosarcoma and discuss treatment strategies and outcomes.

Publication Types:

Case Reports
Review
Review of Reported Cases

PMID: 15233236 [PubMed - indexed for MEDLINE]