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NCI CANCERLIT^® Search: Therapy of Brain Tumor - September 2001

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Last Modified: November 1, 2001

• Thyroid dysfunction as a late effect in childhood medulloblastoma: a comparison of hyperfractionated versus conventionally fractionated craniospinal radiotherapy.

• Correlation between postoperative 3-[(123)I]iodo-L-alpha-methyltyrosine uptake and survival in patients with gliomas.

• [Future trends in the treatment of brain tumors. Padua, 16-17 March 2001]

• Neuro-oncology clinical trials: promise and pitfalls.

• Temozolomide as a second-line systemic regimen in recurrent high-grade glioma: a phase II study.

• Multicenter phase II trial of temozolomide in patients with glioblastoma multiforme at first relapse.

• Transcranial electrical motor evoked potential monitoring for brain tumor resection.

• Multimodal cranial neuronavigation: direct integration of functional magnetic resonance imaging and positron emission tomography data: technical note.

• Reirradiation of primary brain tumours: survival, clinical response and prognostic factors.

• Clinical thermometry, using the 27 MHz multi-electrode current-source interstitial hyperthermia system in brain tumours.

• [Oncolytic adenovirus for the treatment of cerebral tumors: past, present and future]

• Intrathecal chemotherapy with antineoplastic agents in children.

• Surgical treatment of intracranial cavernous angiomas.

• Intraoperative wake-up procedure with propofol and laryngeal mask for optimal excision of brain tumour in eloquent areas.

• Rehabilitation of persons with central nervous system tumors.

• Tumor- and treatment-related side effects after multimodal therapy of childhood intracranial germ cell tumors.

• Second surgery for recurrent pilocytic astrocytoma in children.

• The community integration questionnaire with new scoring guidelines: concurrent validity and need for appropriate norms.

• Clinical trials of adenoviral-mediated suicide gene therapy of malignant gliomas.

• Patient dosimetry after 131I-MIBG therapy for neuroblastoma and carcinoid tumours.

• The risk of haemorrhage associated with early postoperative heparin administration after intracranial surgery.

• Thalidomide as an anti-angiogenic agent in relapsed gliomas.

• Intra-arterial cisplatin plus oral etoposide for the treatment of recurrent malignant glioma: a phase II study.

• Intraoperative magnetic resonance imaging: considerations for the operating room of the future.

• An Australian experience with temozolomide for the treatment of recurrent high grade gliomas.

• Intra-operative MRI-guided approaches to the pediatric posterior fossa tumors.

• Gene therapy of brain and endocrine tumors.

• [Chemotherapy for gliomas based on the expression levels of drug resistant genes]

• The impact of an armless frameless neuronavigation system on routine brain tumour surgery: a prospective analysis of 51 cases.

• A population-based study of glioblastoma multiforme.

• Stereotactic radiotherapy for pediatric intracranial germ cell tumors.

• Phase II radiation therapy oncology group trial of weekly paclitaxel and conventional external beam radiation therapy for supratentorial glioblastoma multiforme.

• Dose-escalation with proton/photon irradiation for Daumas-Duport lower-grade glioma: results of an institutional phase I/II trial.

• Patterns of failure following CT-based 3-D irradiation for malignant glioma.

• Chemoreduction for retinoblastoma may prevent intracranial neuroblastic malignancy (trilateral retinoblastoma).

• Clinical research: the power of the nurse.

CancerMail from the National Cancer Institute

1
UI - 21376184
AU - Ricardi U; Corrias A; Einaudi S; Genitori L; Sandri A; di Montezemolo LC; Besenzon L; Madon E; Urgesi A
TI - Thyroid dysfunction as a late effect in childhood medulloblastoma: a comparison of hyperfractionated versus conventionally fractionated craniospinal radiotherapy.
SO - Int J Radiat Oncol Biol Phys 2001 Aug 1;50(5):1287-94
AD - Department of Radiation Oncology, Regina Margherita Children's Hospital, Turin, Italy. umberto.ricardi@esanet.it
PURPOSE: Primary hypothyroidism is a common sequela of craniospinal radiotherapy in the treatment of childhood medulloblastoma. Due to the strong radiobiologic rationale, hyperfractionation can reduce the delayed effects of radiation injury. METHODS AND MATERIALS: The authors compared the incidence of thyroid dysfunction after conventionally fractionated radiotherapy (Group A, n = 20 patients) vs. hyperfractionated radiotherapy (Group B, n = 12 patients) in a group of pediatric patients with posterior fossa primitive neuroectodermal tumor (PNET). RESULTS: The mean age at the time of tumor diagnosis was 7.4 years in Group A and 8.4 years in Group B. Thyroid function was evaluated yearly, with ultrasonographic examination every 2 years. The patients were followed after diagnosis for a mean of 10.8 years for Group A and 6.0 years for Group B. Approximately 80% of the Group A (16/20) and 33.3% of the Group B (4/12) patients developed primary hypothyroidism within a similar period after irradiation (4.2 vs. 3.5 years, respectively). Analysis by cumulative incidence function demonstrated a significant difference in the risk of developing thyroid dysfunction between these two groups of patients (p < 0.05). Ultrasonography showed reduced thyroid volume in 7 Group A patients and structural changes in 21 patients (17 Group A, 4 Group B cases); a thyroid benign nodule was detected in 2 Group A patients. CONCLUSIONS: The current study findings suggest that the use of hyperfractionated craniospinal radiotherapy in the treatment of childhood medulloblastoma is associated with a lower risk of these patients' developing late thyroid dysfunction.

2
UI - 21376314
AU - Weber WA; Dick S; Reidl G; Dzewas B; Busch R; Feldmann HJ; Molls M; Lumenta CB; Schwaiger M; Grosu AL
TI - Correlation between postoperative 3-[(123)I]iodo-L-alpha-methyltyrosine uptake and survival in patients with gliomas.
SO - J Nucl Med 2001 Aug;42(8):1144-50
AD - Department of Nuclear Medicine, Technische Universitaet Muenchen, Munich, Germany.
The aim of this study was to evaluate the prognostic value of SPECT imaging using the amino acid analog 3-[(123)I]iodo-L-alpha-methyltyrosine (IMT) in patients with gliomas. METHODS: One hundred fourteen consecutive patients with newly diagnosed gliomas were examined by IMT SPECT (low-grade glioma, n = 12; anaplastic astrocytoma or oligodendroglioma, n = 46; glioblastoma, n = 56). Seventy-one of these patients had undergone tumor resection 4-6 wk before SPECT imaging (group A). Forty-three patients with unresectable tumors were examined after stereotactic biopsy (group B). IMT uptake at the site of the tumor was assessed visually and quantified relative to a contralateral reference region (IMT uptake ratio). After IMT SPECT, all patients were treated with conformal radiotherapy. The median follow-up time was 27 mo. RESULTS: In group A, focal IMT uptake at the resection site was visible in 52 of 71 patients (73%). Median survival was only 13 mo in these patients, whereas median survival was reached in patients without focal IMT uptake (P = 0.02). Furthermore, the intensity of IMT uptake significantly correlated with survival: patients with an IMT uptake ratio > 1.7 were at a 4.6 times higher risk of death than were patients with a lower IMT uptake (P < 0.001). The IMT uptake ratio remained a significant prognostic factor when age and grading were included in a multivariate model. In contrast, IMT uptake did not correlate with survival in group B (P = 0.95). CONCLUSION: In patients with unresectable high-grade gliomas, IMT uptake appears not to correlate with the biologic aggressiveness of tumor cells. Nevertheless, the clear association between focal IMT uptake after tumor resection and poor survival suggests that IMT is a specific marker for residual tumor tissue. Therefore, IMT SPECT is expected to become a valuable tool for the planning and monitoring of local therapeutic modalities.

3
UI - 21395132
AU - Basso U; Longo F; Mansueto G
TI - [Future trends in the treatment of brain tumors. Padua, 16-17 March 2001]
SO - Tumori 2001 May-Jun;87(3):A15-36

4
UI - 21193587
AU - Gilbert MR
TI - Neuro-oncology clinical trials: promise and pitfalls.
SO - Ann Oncol 2001 Feb;12(2):149-50

5
UI - 21193605
AU - Brandes AA; Ermani M; Basso U; Amista P; Berti F; Scienza R; Rotilio A; Pinna G; Gardiman M; Monfardini S
TI - Temozolomide as a second-line systemic regimen in recurrent high-grade glioma: a phase II study.
SO - Ann Oncol 2001 Feb;12(2):255-7
AD - Department of Medical Oncology, Azienda Ospedaliera, Padova, Italy. brandes@ux1.unipd.it
BACKGROUND: To investigate the efficacy of temozolomide in relation to response rate, toxicity, time to progression. and median survival time, a phase II study was conducted in patients with recurrent high-grade glioma following surgery plus radiotherapy and first-line chemotherapy based on nitrosourea, procarbazine and vincristine. PATIENTS AND METHODS: Forty-one patients with high-grade glioma, at second recurrence or progression, of which twenty-two (54%) had glioblastoma multiforme, ten (24%) anaplastic astrocytoma, and nine (22%) anaplastic oligodendroglioma were administered temozolomide, 150 mg/m2/daily for five days every four weeks. RESULTS: Response was assessed in 40 patients. The overall response rate (complete + partial response) was 22.5% (95% confidence interval (CI): 9.5%-35%). The median time to progression for all 41 patients was 22.3 weeks; progression-free survival at 6 and 12 months was 48.5% and 34.7%, respectively. Median survival time was 37.1 weeks with 80.2% at 6 and 34.9% survival at 12 months. CONCLUSIONS: On multivariate analysis, response to previous treatment was significant (P = 0.03) for time to progression and Karnofsky performance score for overall survivall (P = 0.002). Temozolomide gave a moderate response rate with acceptable toxicity as second-line chemotherapy in patients with recurrent high-grade glioma.

6
UI - 21193606
AU - Brada M; Hoang-Xuan K; Rampling R; Dietrich PY; Dirix LY; Macdonald D; Heimans JJ; Zonnenberg BA; Bravo-Marques JM; Henriksson R; Stupp R; Yue N; Bruner J; Dugan M; Rao S; Zaknoen S
TI - Multicenter phase II trial of temozolomide in patients with glioblastoma multiforme at first relapse.
SO - Ann Oncol 2001 Feb;12(2):259-66
AD - The Royal Marsden Hospital, Surrey, UK. mbrada@icr.ac.uk
BACKGROUND: Recurrent glioblastoma multiforme (GBM) is resistant to most therapeutic endeavors, with low response rates and survival rarely exceeding six months. There are no clearly established chemotherapeutic regimens and the aim of treatment is palliation with improvement in the quality of life. PATIENTS AND METHODS: We report an open-label, uncontrolled, multicenter phase II trial of temozolomide in 138 patients (intent-to-treat [ITT] population) with glioblastoma multiforme at first relapse and a Karnofsky performance status (KPS) > or = 70. One hundred twenty-eight patients were histologically confirmed with GBM or gliosarcoma (GS) by independent central review. Chemotherapy-naive patients were treated with temozolomide 200 mg/m2/day orally for the first five days of a 28-day cycle. Patients previously treated with nitrosourea-containing adjuvant chemotherapy received 150 mg/m2/day for the first five days of a 28-day cycle. In the absence of grade 3 or 4 toxicity, patients on the 150 mg/m2 dose schedule were eligible for a 200 mg/m2 dose on the next cycle. RESULTS: The primary endpoint was six-month progression-free survival assessed with strict radiological and clinical criteria. Secondary endpoints included radiological response and Health-related Quality of Life (HQL). Progression-free survival at six months was 18% (95% confidence interval (CI): 11%-26%) for the eligible-histology population. Median progression-free survival and median overall survival were 2.1 months and 5.4 months, respectively. The six-month survival rate was 46%. The objective response rate (complete response and partial response) determined by independent central review of gadolinium-enhanced magnetic resonance imaging (MRI) scans was 8% for both the ITT and eligible-histology populations, with an additional 43% and 45% of patients, respectively, having stable disease (SD). Objectively assessed response and maintenance of a progression-free status were both associated with HQL benefits (characterized by improvements over baseline in HQL domains). Temozolomide had an acceptable safety profile, with only 9% of therapy cycles requiring a dose reduction due to thrombocytopenia. There was no evidence of cumulative hematologic toxicity. CONCLUSIONS: Temozolomide demonstrated modest clinical efficacy, with an acceptable safety profile and measurable improvement in quality of life in patients with recurrent GBM. The use of this drug should be explored further in an adjuvant setting and in combination with other agents.

7
UI - 21232083
AU - Zhou HH; Kelly PJ
TI - Transcranial electrical motor evoked potential monitoring for brain tumor resection.
SO - Neurosurgery 2001 May;48(5):1075-80; discussion 1080-1
AD - Department of Anesthesiology, New York University Medical Center, New York 10016, USA.
OBJECTIVE: This study was designed to examine whether transcranial electrical motor evoked potential (MEP) monitoring is safe, feasible, and valuable for brain tumor surgery. METHODS: Fifty consecutive patients undergoing brain tumor resection were studied, using nitrous oxide/propofol anesthesia. MEPs were continuously recorded throughout surgery, using a Sentinel 4 evoked potential system (Axon Systems, Inc., Hauppauge, NY). The MEPs were elicited by transcranial electrical stimulation (train of 5; stimulation rate, 0.5-2 Hz; square wave pulse with a time constant of 0.5 ms; stimulation intensity, 40-160 mA) through spiral electrodes placed over the primary motor cortex and were recorded by needle electrodes inserted into the contralateral orbicularis oris, biceps, abductor pollicis brevis, and anterior tibialis muscles. When MEP amplitudes decreased by more than 50%, MEP stimulation was repeated, with increased stimulation intensity, and MEP changes were reported to the surgeon. The motor function of each patient was examined before and after surgery, using a reproducible scale. The relationship between MEP amplitude decreases and worsening motor status was analyzed using linear regression. RESULTS: Preoperative neurological examinations revealed mild to moderate motor deficits (2/5 to 4/5) for 38% of patients (19 of 50 patients). Most of the patients (96%) exhibited recordable baseline MEPs. Persistent MEP decreases of more than 50% were noted for eight patients (16%) (11 muscles). The MEPs were completely abolished in two patients (three muscles). The degree of postoperative worsening of motor status was correlated with the degree of intraoperative MEP amplitude reduction (r = -0.864; P < 0.001). CONCLUSION: Persistent intraoperative MEP reductions of more than 50% were associated with postoperative motor deficits. The degree of MEP amplitude reduction was correlated with postoperative worsening of motor status. Transcranial electrical MEP monitoring is feasible, safe, and valuable for brain tumor surgery.

8
UI - 21232099
AU - Braun V; Dempf S; Tomczak R; Wunderlich A; Weller R; Richter HP
TI - Multimodal cranial neuronavigation: direct integration of functional magnetic resonance imaging and positron emission tomography data: technical note.
SO - Neurosurgery 2001 May;48(5):1178-81; discussion 1181-2
AD - Department of Neurosurgery, University of Ulm, Gunzburg, Germany. veit.braun@medizin.uni-ulm.de
OBJECTIVE: This is the first report of the direct integration of functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) data into cranial neuronavigation. METHODS: In a patient with a left precentral oligodendroglioma (World Health Organization Grade III), the Zeiss MKM system (Carl Zeiss Co., Oberkochen, Germany) was used for navigation based on thin-slice, T1-weighted, contrast-enhanced magnetic resonance imaging (MRI) scans. fMRI and methionine PET data were integrated by landmark matching, with reference to skin fiducials. RESULTS: The inaccuracy of the image fusion between fMRI and T1-weighted MRI data was 1.7 mm, that between PET and T1-weighted MRI data was 4.3 mm, and that for the subsequent registration of the navigation was 1.2 mm. The correct fMRI localization of the precentral gyrus was intraoperatively verified by cortical somatosensory evoked potential (phase-reversal) monitoring. Although the tumor was not clearly defined in the MRI scans, [11C]methionine PET demonstrated a clear tumor border, enabling us to achieve gross total tumor removal without postoperative functional deficits. CONCLUSION: Functional neuronavigation permits observation and preservation of relevant brain areas. Other functional areas (such as short-term memory areas) that can be detected only by fMRI might also warrant future monitoring. The simultaneous integration of fMRI and PET data adds a new dimension to cranial neuronavigation, enabling the observation of tumors in relation to functional cortical areas (in our case, the motor strip).

9
UI - 21225871
AU - Veninga T; Langendijk HA; Slotman BJ; Rutten EH; van der Kogel AJ; Prick MJ; Keyser A; van der Maazen RW
TI - Reirradiation of primary brain tumours: survival, clinical response and prognostic factors.
SO - Radiother Oncol 2001 May;59(2):127-37
AD - Department of Radiation Oncology, RADIAN, Joint Centre for Radiation Oncology Arnhem-Nijmegen, University Hospital Nijmegen, P.O. Box 9101, 6500 HB, The, Nijmegen, Netherlands.
BACKGROUND AND PURPOSE: First, the aim was to determine the survival and quality of life after reirradiation of relapsing primary malignant brain tumours. The second aim was to assess the influence of a set of potentially prognostic factors on survival. MATERIALS AND METHODS: Forty-two patients received reirradiation for recurring primary brain tumours. The interval between the two consecutive treatments was at least 1 year. External beam irradiation for the initial and recurrent tumour was usually delivered with two opposing lateral fields or two wedged fields in orthogonal directions. The median physical doses of the first and second radiation course were 50 and 46 Gy, respectively. The median cumulative biological equivalent doses (BED) were 200.4 (alpha/beta = 2 Gy) and 115.2 Gy (alpha/beta = 10 Gy). During follow-up, corticosteroid medication and the WHO-performance were registered at regular intervals. The radiological response was assessed by reviewing all available CT- and MRI-films. Potentially prognostic factors with respect to survival were evaluated by both univariate and multivariate analyses. RESULTS: A clinical response (i.e. clinical improvement) was seen in 24% of the patients. Of the evaluable patients, nearly one-third showed a complete (8%) or partial (22%) radiological response. The median overall survival (OS) and progression-free survival (PFS) after retreatment were 10.9 and 8.6 months, respectively. By multivariate analysis, four independent prognostic factors for survival were identified: (1), the WHO-score before retreatment (P = 0.002); (2), the length of the interval between treatments (P = 0.008); (3), the tumour histology; and (4), the response to initial treatment (P values, 0.04). The median survival times for patients with WHO-scores of 0-1 and > or = 2 were 14.0 and 7.4 months, respectively. Patients with oligodendrogliomas had a median OS of 27.5 months, whereas patients with astrocytomas had a median OS of 6.9 months after retreatment. Long-term complications of retreatment were seen in three patients, all of whom had a cumulative BED(2) of > 204 Gy (with alpha/beta = 2 Gy). The quality of life after retreatment, however, was well preserved in the majority of patients. They remained ambulant and capable of self-care until the time of progression which occurred after 8.6 months (median PFS). CONCLUSIONS: After an initial treatment with radiation up to tolerance levels of normal brain tissue, reirradiation of recurring primary brain tumours seems feasible. During the time until clinical progression, patients remained independent with a reasonable quality of life.

10
UI - 21225885
AU - Kaatee RS; Nowak PC; van der Zee J; de Bree J; Kanis BP; Crezee H; Levendag PC; Visser AG
TI - Clinical thermometry, using the 27 MHz multi-electrode current-source interstitial hyperthermia system in brain tumours.
SO - Radiother Oncol 2001 May;59(2):227-31
AD - Division of Clinical Physics, Department of Radiotherapy, Daniel den Hoed Cancer Center, University Hospital Rotterdam, Groene Hilledijk 301, 3075 EA, The, Rotterdam, Netherlands.
BACKGROUND AND PURPOSE: In interstitial hyperthermia, temperature measurements are mainly performed inside heating applicators, and therefore, give the maximum temperatures of a rather heterogeneous temperature distribution. The problem of how to estimate lesion temperatures using the multi-electrode current-source interstitial hyperthermia (MECS-IHT) system in the brain was studied. MATERIALS AND METHODS: Temperatures were measured within the electrodes and in an extra catheter at the edge of a 4 x 4 x 4.5 cm(3) glioblastoma multiforme resection cavity. From the temperature decays during a power-off period, information was obtained about local maximum and minimum tissue temperatures. The significance of these data was examined through model calculations. RESULTS: Maximum tissue temperatures could be estimated roughly by switching off all electrodes for about 5 s. Model calculations showed that the minimum tissue temperatures near a certain afterloading catheter correspond well with the temperature of the applicator inside, about 1 min after this applicator was switched off. CONCLUSIONS: Although the electrode temperatures read during heating are not suitable to assess the temperature distribution, it is feasible to heat the brain adequately using the MECS-IHT system with extra sensors outside the electrodes and/or application of decay methods.

11
UI - 21232432
AU - Alemany R; Gomez-Manzano C; Fueyo J
TI - [Oncolytic adenovirus for the treatment of cerebral tumors: past, present and future]
SO - Neurologia 2001 Mar;16(3):122-7
AD - Division of Human Gene Therapy. University of Alabama at Birmingham. Birmingham, USA.
The transfer of genetic material as a therapy (gene therapy) is one of the experimental treatments being considered in patients with brain tumors resistant to any conventional treatment. Several clinical trials have proved that the intratumoral administration of genes is fairly safe for patients, however the anti-tumor effect of these strategies remains suboptimal. One of the main problems in cancer gene therapy is the failure of current vectors to achieve enough tumor transduction in a suficient number of cells. This is even true for vectors derived from viruses with high infectivity ability such as adenovirus. For that reason, current strategies explore the use of adenoviruses able to replicate and spread throughout the tumor. The local, intratumoral injection of adenovirus is an especially suitable strategy for gliomas because these tumors, although infiltrative, rarely metastasize. Two approaches have been used to generate tumor-selective replicative adenoviruses: use of tumor-specific promoters to regulate the expression of viral genes, and the deletion of the viral functions required for the activation of the cell cycle. Since normal cells surrounding giomas are quiescent, the second strategy is particularly attractive to develop new treatments for brain tumors.

12
UI - 21253887
AU - Ruggiero A; Conter V; Milani M; Biagi E; Lazzareschi I; Sparano P; Riccardi R
TI - Intrathecal chemotherapy with antineoplastic agents in children.
SO - Paediatr Drugs 2001;3(4):237-46
AD - Division of Paediatric Oncology, Catholic University, Rome, Italy.
Intrathecal chemotherapy with antineoplastic agents is mainly utilised in children with leukaemia and lymphoma, and in selected brain tumours. In these diseases, intrathecal use is restricted to methotrexate (MTX), cytosine arabinoside (Ara-C) and corticosteroids. A number of other agents are, at the present time, under evaluation. Intrathecal MTX administered sequentially with systemic high dose MTX infusion prolongs therapeutic cerebral spinal fluid (CSF) levels of the drug. Prolonged therapeutic CSF levels can also be achieved by giving repeated small intrathecal doses of MTX over an extended period in selected patients, with an implanted Ommaya reservoir. In the CSF, the metabolic inactivation of Ara-C is significantly lower than in plasma with a CSF clearance similar to the rate of CSF bulk flow. A slow-release formulation of Ara-C may be given intrathecally, resulting in a prolonged cytotoxic concentration in the CSF. CNS relapse and neurotoxicity in patients with acute lymphoblastic leukaemia, especially younger children, may be reduced by using age-related dosing of intrathecal MTX and Ara-C. Hydrocortisone is used in combination with MTX and Ara-C for so-called 'triple intrathecal chemotherapy' in the treatment of meningeal leukaemia. Intrathecal thiotepa does not appear to be advantageous over systemic administration in patients with brain and meningeal leukaemia. Monoclonal antibodies, reactive with tumour-associated antigens, can be used as delivery systems for chemotherapeutic agents and radionuclides. However, the development of this new approach is currently under evaluation in larger clinical studies. Neurological adverse effects may be expected with intrathecal chemotherapy and are increased by high dose systemic therapy, concomitant cranial radiotherapy or meningeal infiltration by neoplastic cells. Inadvertant intrathecal administration of antineoplastic agents that are indicated for systemic administration only, is dangerous and may result in a fatal outcome.

13
UI - 21280982
AU - Attar A; Ugur HC; Savas A; Yuceer N; Egemen N
TI - Surgical treatment of intracranial cavernous angiomas.
SO - J Clin Neurosci 2001 May;8(3):235-9
AD - School of Medicine, Department of Neurosurgery, Ankara University, Ankara, Turkey.
We present a surgical series of 35 patients (25 males and 10 females) with histopathologically verified intracranial cavernous angiomas. The 35 malformations were located as follows: 21 were in the cerebral hemispheres; 4 in the lateral ventricles, 4 in the brain stem; and 6 in the cerebellum. Seizures and focal neurological deficits were the main clinical features observed in patients with intracranial cavernous angiomas. A number of these vascular malformations were misdiagnosed by computerized tomography. In the last 10 years, magnetic resonance imaging has been the most sensitive method for detecting these lesions. Thirty-five cavernous angiomas were treated surgically; in 33 patients a complete excision, and in 2 patients subtotal excision were obtained. One of the patients died one year after the operation. The overall outcome was good in all of the 34 remaining patients, resulting in improved seizure control or neurological deficit. The rationale for neurologic differential diagnosis and surgical treatment and follow up results are discussed. Copyright 2001 Harcourt Publishers Ltd.

14
UI - 21280986
AU - Fukaya C; Katayama Y; Yoshino A; Kobayashi K; Kasai M; Yamamoto T
TI - Intraoperative wake-up procedure with propofol and laryngeal mask for optimal excision of brain tumour in eloquent areas.
SO - J Clin Neurosci 2001 May;8(3):253-5
AD - Department of Neurological Surgery, Nihon University School of Medicine, Tokyo 173, Japan. chikashi@tb3.so-net.ne.jp
This is the first thesis describing a new technique for awake craniotomy using a laryngeal mask. Awake craniotomy with propofol infusion has become increasingly popular for the optimal excision of brain tumours located in eloquent areas. During awake craniotomy, tracheal intubation is not performed and propofol infusion is limited to within doses which render the patient just sedated. This asleep-awake procedure is occasionally associated with difficulty in controlling brain volume, especially in patients with a significant mass effect of their brain tumours, since sufficient sedation with propofol tends to cause hypercapnea. We report an intraoperative wake-up procedure employing a laryngeal mask, which enables general anaesthesia to be performed at a sufficient dose of propofol and with control of the brain volume under mechanically assisted ventilation. Before the beginning of cortical mapping, propofol infusion is completely terminated, so allowing the patient to wake up within 5-15 min. Following completion of the tumour excision, general anaesthesia is re-induced at a sufficient dose of propofol. The laryngeal mask can be temporarily removed and repositioned with ease, if necessary. In our experience, this technique is applicable for the optimal excision of brain tumours, especially in patients who are very obese or those who have very large lesions. Copyright 2001 Harcourt Publishers Ltd.

15
UI - 21409824
AU - Kirshblum S; O'Dell MW; Ho C; Barr K
TI - Rehabilitation of persons with central nervous system tumors.
SO - Cancer 2001 Aug 15;92(4 Suppl):1029-38
AD - Department of Physical Medicine and Rehabilitation, New Jersey Medical School, Newark, New Jersey, USA. skirshblum@kessler-rehab.com
A tumor that affects the central nervous system can have a dramatic impact on the individual affected, as well as his or her family and friends. The tumor, regardless of extent or location, may affect the physical, social, vocational, and emotional capabilities of the individual. Basic aspects of rehabilitation for patients with tumors affecting the brain and spinal cord are reviewed in this article. The authors have found that the same principles of neurorehabilitation applied to persons with traumatic brain injury, stroke, and traumatic spinal cord injury are equally appropriate for persons with brain and spinal cord tumors. These principles include the prevention of medical complications; the treatment of medical problems such as pain, spasticity, and neuropathic bowel and bladder; and the improvement of patients' mobility and activities of daily living. Rehabilitation specialists can help prevent complications, maximize function, and improve the quality of life for patients with central nervous system tumors. Copyright 2001 American Cancer Society.

16
UI - 21230847
AU - Benesch M; Lackner H; Schagerl S; Gallistl S; Frey EM; Urban C
TI - Tumor- and treatment-related side effects after multimodal therapy of childhood intracranial germ cell tumors.
SO - Acta Paediatr 2001 Mar;90(3):264-70
AD - Division of Paediatric Haematology and Oncology, University of Graz, Austria. martin.benesch@klinikum-graz.at
Multimodality treatment approaches have dramatically improved the outcome of patients with intracranial germ cell tumors and are resulting in an increasing number of long-term survivors. The aim of the present study was to evaluate prospectively the development of side effects in children, adolescents and young adults after treatment for intracranial germ cell tumors. Nine patients with a median age of 14 y at diagnosis and a median follow-up of 7.25 y underwent a detailed long-term evaluation including physical and neuro-ophthalmologic examinations, routine laboratory and endocrine stimulation tests, neuropsychometric testing, audiometry and spirometry at repeated intervals. Endocrine deficiencies requiring hormone replacement therapy occurred in all patients. Neuro-ophthalmologic side effects were observed in 8 of the 9 patients, urinary electrolyte wasting in 4 of the 9, alopecia in 3 of the 9 and high-frequency hearing loss in 2 of the 9. Neuropsychologic examinations revealed pathologic results in all five tested patients. CONCLUSION: The present study indicates that former intracranial germ cell tumor patients suffer from remarkable long-term side effects, and that some of these late effects can develop or worsen months or years after cessation of oncologic therapy. Since life quality is an important parameter of cancer survival, careful follow-up of long-term survivors is mandatory, aimed at counteracting side effects as early as possible and therefore at minimizing long-term morbidity, which may considerably compromise quality of life.

17
UI - 21317193
AU - Bowers DC; Krause TP; Aronson LJ; Barzi A; Burger PC; Carson BS; Weingart JD; Wharam MD; Melhem ER; Cohen KJ
TI - Second surgery for recurrent pilocytic astrocytoma in children.
SO - Pediatr Neurosurg 2001 May;34(5):229-34
AD - The Johns Hopkins Oncology Center and Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, Md., USA.
Pilocytic astrocytoma (PA) is the most common childhood brain tumor. In cases where the tumor progresses or recurs following primary surgical resection, the appropriate treatment is unclear. Options include chemotherapy, radiation therapy, surgical resection or a combination thereof. To analyze the utility of further surgery, we performed a retrospective, single-institution review of pediatric patients with recurrent PAs from 1990 to 1999 who were treated with a second surgical resection. Patients were excluded if they received adjuvant chemotherapy or radiation therapy. Twenty cases were identified. Tumor locations included: cerebral hemisphere (3), cerebellum (7), optic pathway/hypothalamus (5), thalamus (1) and brainstem (4). The indication for 4 surgeries included an enlarging tumor-associated cyst. At second surgery, 10 of 20 patients had a gross total resection (GTR), 2 a near total resection (NTR), and the remaining 8 patients had a subtotal resection (STR). No patients have died. Two of 10 tumors after GTR, 0 of 2 tumors after NTR, and 7 of 8 tumors after STR had second recurrence/progression at a mean of 15 months (range 4-33 months) following second surgery. The remaining 11 patients are recurrence/progression-free at a mean of 40.7 months (range 19-119 months). Surgery for tumors or midline structures rarely resulted in a GTR (1 of 10 cases). Surgery for tumors located in the cerebral hemispheres or cerebellum resulted in GTR or NTR in all cases and can result in long periods of progression-free survival without further adjuvant treatment. Copyright 2001 S. Karger AG, Basel

18
UI - 21378233
AU - Kaplan CP
TI - The community integration questionnaire with new scoring guidelines: concurrent validity and need for appropriate norms.
SO - Brain Inj 2001 Aug;15(8):725-31
AD - 1524 Copperwood Pl., Carmel, IN 46033, USA.
OBJECTIVE: To investigate the influence of demographic variables and concurrent validity when new scoring guidelines are used with the Community Integration Questionnaire (CIQ). METHOD: Thirty-three adult outpatients with biopsy confirmed malignant brain tumours were evaluated prior to chemotherapy. In contrast to TBI subjects, the brain tumour sample was older (x age= 46.3 years), better educated (x = 13.7 years); and gender was more evenly represented (16 male, 17 female).RESULTS: Demographic variables mediated CIQ scores. Gender effects were still seen, with women significantly higher on Home Integration (r = 0.40, p < 0.05). Older subjects had lower CIQ scores: CIQ total (r = -0.54, p < 0.005); Home Integration (r = -0.42, p < 0.01); Social Integration (r = -0.44, p < -0.005); and Productivity (r = -0.45, p < 0.005). More education was related to higher CIQ total (r = 0.31, p < 0.05); Social Integration (r = 0.30, p < 0.05); and Productivity (r = 0.35, p < 0.05). Significant relationships were seen between CIQ scores and both the Social Activity and Inactivity subscales of the Chronic Illness Problem Inventory (r = -0.43, p < 0.005 and r = -0.68, p < 0.005, respectively). CONCLUSIONS: CIQ norms for age, education, sex, and marital status are strongly recommended. Moderate concurrent validity remained with new scoring guidelines.

19
UI - 21428612
AU - Nanda D; Driesse MJ; Sillevis Smitt PA
TI - Clinical trials of adenoviral-mediated suicide gene therapy of malignant gliomas.
SO - Prog Brain Res 2001;132():699-710
AD - Department of Neurosurgery, University Hospital Rotterdam, PO Box 5201, 3008 AE Rotterdam, The Netherlands.

20
UI - 21236705
AU - Monsieurs MA; Thierens HM; Vral A; Brans B; De Ridder L; Dierckx RA
TI - Patient dosimetry after 131I-MIBG therapy for neuroblastoma and carcinoid tumours.
SO - Nucl Med Commun 2001 Apr;22(4):367-74
AD - Department of Biomedical Physics & Radiation Dosimetry, University of Ghent, Belgium. myriam.monsieurs@rug.ac.be
AIM: The aim of the study was to determine the equivalent total body dose (ETBD) using the cytokinesis-blocked micronucleus assay in 22 131 I-meta-iodobenzylguanidine (131 I-MIBG) therapies (18 neuroblastoma, mean 5097 MBq, SD 1591; and four carcinoid tumours, mean 7681 MBq, SD 487). The results are correlated with the total body radiation dose according to the Medical Internal Radiation Dosimetry (MIRD) formalism. METHODS: For each patient, blood samples were taken immediately before and 1 week after 131I-MIBG therapy. The first blood sample was irradiated in vitro with 60Co gamma-rays to determine the dose-response curve. Micronuclei were scored in 1000 binucleated cells. By using the dose-response curve the ETBD was derived from the increase in micronuclei after 131I-MIBG therapy (second blood sample). Based on three consecutive biplanar scans taken at 3, 6 and 9 days post-administration respectively, the total body dose following the MIRD formalism was calculated. RESULTS: The micronucleus assay was evaluable in only 14 out of 22 131I-MIBG therapies due to cell division inhibition caused by previous chemotherapy treatments and lymphocyte dilution due to blood transfusions given shortly after 131I-MIBG therapy. For these 14 therapies, the mean micronucleus yield after 131I-MIBG therapy was significantly increased (P < 0.01) with a mean of 92 (SD 77) for neuroblastoma patients and with a mean of 35 (SD 8) for carcinoid patients. The increase observed in the present study is greater than previously observed after 131I therapy and 89Sr therapy but much lower than after external beam radiotherapy. For all patients treated with multiple therapies, the initial increase in micronucleus yield had at least partially recovered by the time of the next therapy. This might be explained by an increased turnover of lymphocytes. A mean ETBD of 0.95 Gy (SD 0.55) for neuroblastoma patients and a mean of 0.46 Gy (SD 0.09) for carcinoid patients was calculated. A reasonable correlation (R = 0.87) between the ETBD and the MIRD dose was obtained. The slope value of 0.75 can be explained by the low dose rate effect. CONCLUSIONS: The observation in the present study of important inter-individual variability in the total body dose, with the possibility of high dose values, suggests the necessity of individual dosimetry when administering 131I-MIBG therapy, especially considering that generally more than one therapy is given to each patient.

21
UI - 21243846
AU - Raabe A; Gerlach R; Zimmermann M; Seifert V
TI - The risk of haemorrhage associated with early postoperative heparin administration after intracranial surgery.
SO - Acta Neurochir (Wien) 2001;143(1):1-7
AD - Department of Neurosurgery, Johann Wolfgang Goethe University, Frankfurt am Main, Germany.
BACKGROUND: To analyse the rate of postoperative haemorrhage during a 4-year period of early postoperative administration (< 24 hours) of fractionated heparin plus compression stockings in a large cohort of patients undergoing intracranial surgery. METHOD: A total of 1564 patients who underwent intracranial surgery at our institution were included in our study. 1197 of the 1564 patients (77%) had major intracranial surgery (group 1). Group 2 was made up of 367 patients in whom ventriculoperitoneal shunting or external ventriculostomy was performed (minor intracranial procedures). All patients were investigated retrospectively for the occurrence of major postoperative haemorrhage confirmed by CT scanning and requiring surgical evacuation. The protocol for prophylaxis of thrombo-embolic events included early (< 24 hours) postoperative fractionated low-dose heparin (3 x 5000 IE subcutaneously) until discharge plus intra- and postoperative compression stockings. FINDINGS: Major postoperative haemorrhages were observed in 31 of the 1564 patients (2.0%). In three patients, the haemorrhage occurred on the day of surgery before the administration of heparin. The haemorrhage rate of patients receiving heparin was 1.8% (28/1564). All haemorrhages occurred in patients undergoing major intracranial procedures (group 1; 31/1197; 2.6%). There was no haemorrhage in minor intracranial procedures (group 2; 0/367; 0%). INTERPRETATION: Although retrospective, this is to date the largest study supporting the concept of postoperative pharmacological thrombo-embolic propylaxis in patients undergoing intracranial surgery. The question as to whether pharmacological prophylaxis is beneficial for a given patient can only be answered by weighing the risk reduction of thrombo-embolic events against the risk increase of postoperative haemorrhage associated with different surgical procedures and heparin protocols.

22
UI - 21247514
AU - Short SC; Traish D; Dowe A; Hines F; Gore M; Brada M
TI - Thalidomide as an anti-angiogenic agent in relapsed gliomas.
SO - J Neurooncol 2001 Jan;51(1):41-5
AD - Unit of Neuro-Oncology, The Institute of Cancer Research and The Royal Marsden NHS Trust, Sutton, Surrey, UK. susan.short@rmh.nthames.nhs.uk
BACKGROUND: Thalidomide (alpha-phthalimidoglutarimide), a synthetic sedative drug, has anti-angiogenic properties due to inhibition of growth-factor mediated neovascularisation and has been shown to inhibit tumour growth in experimental solid tumour models. AIM: To assess response of recurrent malignant gliomas to thalidomide. METHODS: Eighteen patients with recurrent gliomas were enrolled to an open, non-randomised phase II trial between October 1997 and December 1999. All patients had failed following treatment with radiotherapy and chemotherapy with PCV and/or temozolomide regimens. Eleven patients had high-grade gliomas de novo and 7 high-grade gliomas following transformation of low-grade gliomas. Thalidomide was prescribed at 100 mg/day p.o. continuously. Response was assessed at 4-weekly intervals. Disease progression was defined as neurological deterioration and/or radiological evidence of increased tumour size. Treatment was discontinued at the time of disease progression, or if toxicity occurred, or at patients' request. RESULTS: Thalidomide was prescribed for a median of 42 days (range 7-244). Treatment was discontinued due to toxicity (peripheral sensory neuropathy) in 1 patient. Six patients died before response could be fully assessed and are classified as non-responders. Of 12 who continued treatment for more than 4 weeks, 1 patient had clinical and radiological response (PR), 2 patients had stable disease for 2 and 4 months respectively and 9 patients had disease progression. The median survival from the start of thalidomide was 2.5 months. CONCLUSION: The efficacy of thalidomide in terms of response in recurrent gliomas is low, with a partial response rate of only 6%. Future studies should investigate thalidomide in combination with other agents and at an earlier stage of disease. Methods to assess anti-angiogenic properties such as changes in tumour vasculature could be employed as initial surrogate end-points in the investigation of efficacy.

23
UI - 21247518
AU - Ashby LS; Shapiro WR
TI - Intra-arterial cisplatin plus oral etoposide for the treatment of recurrent malignant glioma: a phase II study.
SO - J Neurooncol 2001 Jan;51(1):67-86
AD - Department of Neurology, Barrow Neurological Institute, Phoenix, Arizona 85013, USA.
Twenty-five adults with recurrent malignant glioma were enrolled into a phase II clinical study. All patients had undergone surgical resection and had failed radiotherapy and first-line treatment with nitrosourea-based chemotherapy; five had failed second-line chemotherapy. Our objective was to test the efficacy of combining intra-arterially (i.a.) infused cisplatin and oral etoposide. Using conventional angiographic technique to access anterior/posterior cerebral circulation, cisplatin 60 mg/m2 was administered by i.a. infusion on day 1 of treatment. Oral etoposide 50 mg/m2/day was given days 1-21, with a 7 day rest interval between courses. Response to treatment was evaluated in 20 patients. Two patients with anaplastic astrocytoma had partial responses (PR) and six patients experienced stable disease (SD) for an overall response rate (PR +/- SD) of 40%. The median time to disease progression (MTP) following treatment for the responder subgroup was 18 weeks. The median survival time from treatment (MST) for the responders (n = 8) and non-responders (n = 12) was 56.5 weeks and 11 weeks, respectively. Combined i.a. cisplatin and oral etoposide was well-tolerated, but produced an objective response in only a minority of patients. Those considered responders (PR + SD) experienced significant survival advantage when compared to the non-responders. Nonetheless, i.a. delivery of chemotherapy is an expensive and technologically burdensome treatment for most patients to access, requiring proximity to a major center with neuro-oncological and neuroradiological clinical services. This is of special concern for patients suffering recurrent disease with progressive neurological symptoms at a time in their course when quality of life must be safeguarded and palliation of symptoms should be the therapeutic goal. Despite the efforts of previous investigators to use this combination of agents to treat recurrent malignant glioma, we cannot recommend the use of i.a. chemotherapy for salvage treatment of this disease.

24
UI - 21331764
AU - Lipson AC; Gargollo PC; Black PM
TI - Intraoperative magnetic resonance imaging: considerations for the operating room of the future.
SO - J Clin Neurosci 2001 Jul;8(4):305-10
AD - Department of Neurosurgery, Brigham and Women's Hospital and Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Recent technological advances have made possible the introduction of the magnetic resonance imaging (MRI) system into the operating room to guide neurosurgical interventions. We review the possibilities and limitations associated with various open-configuration magnet designs, including systems from the Phillips, Siemens, General Electric, Odin and IMRIS designs. This technology has been shown to be a feasible adjunct to current neurosurgical management of intracranial brain tumors for both biopsy and resection procedures and shows significant potential applications for epilepsy surgery, spine surgery and for minimally invasive interventional techniques. Combined with other surgical planning modalities, intra-operative MRI scanners provide an evolutionary influence on the design of today's operating room. Copyright 2001 Harcourt Publishers Ltd.

25
UI - 21331768
AU - Harris MT; Rosenthal MA; Ashley DL; Cher L
TI - An Australian experience with temozolomide for the treatment of recurrent high grade gliomas.
SO - J Clin Neurosci 2001 Jul;8(4):325-7
AD - Austin and Repatriation Medical Centre, Heidelberg, Victoria, Australia.
Temozolomide has an evolving role in the treatment of high grade gliomas. Recent studies suggest that temozolomide is well tolerated and efficacious. This study retrospectively analysed the activity and toxicity associated with temozolomide at two Australian centres over a 24 month period. Fifty-six patients with recurrent high grade gliomas were treated with temozolomide. Patients received temozolomide orally at 150-200mg/m(2)daily, days 1-5, every 4 weeks. The median number of treatment cycles was 4 (1-12). Of the 56 patients, 15 (27%) achieved complete or partial response and 18 (32%) achieved minor response or stable disease. There were no episodes of febrile neutropenia and temozolomide was generally well tolerated. In conclusion, temozolomide is an active therapy in patients with recurrent high grade glioma and our results concord with published studies. Copyright 2001 Harcourt Publishers Ltd.

26
UI - 21348662
AU - Lam CH; Hall WA; Truwit CL; Liu H
TI - Intra-operative MRI-guided approaches to the pediatric posterior fossa tumors.
SO - Pediatr Neurosurg 2001 Jun;34(6):295-300
AD - Department of Neurosurgery, University of Minnesota, Minneapolis, MN, USA. lamxx023@tcn.umn.edu
INTRODUCTION: The posterior fossa in a child poses a considerable challenge to the neurosurgeon. MRI-guided surgery allows for real time interaction between imaging and the neurosurgeon, not permitted by frameless stereotaxy, and with higher resolution than ultrasound or CT. MATERIALS AND METHODS: The University of Minnesota 1.5 T Phillips interventional MRI was used. From 1997 to 2000, nine posterior fossa intraoperative magnet cases out of eleven were pediatric. The mean age was 6.4 years and the median age 7. Seven midline craniotomies were performed, of which three were re-operations. Two were burr hole placements, one for cyst aspiration and P32 instillation, and the other for tumor biopsy. RESULTS: Two tumors were predominantly in the fourth ventricle, four in the cerebellum, two in the brainstem, and one in the prepontine cystern. Four tumors were juvenile pilocytic astrocytomas, two were anaplastic astrocytomas, and one each was ependymoma, craniopharyngioma cyst, and medulloblastoma. Four patients had complete radiologic resection. Two had maximal resections limited by vital structures. P32 instillation and tumor biopsy were done in a single pass. Follow-up ranged from 3 months to 1.4 years. The cyst that was aspirated and had P32 instillation remains absent. The two mortalities were in the patients with medulloblastoma and anaplastic astrocytoma. There were no intra-operative mortalities. The other patient with anaplastic astrocytoma progressed. The remainder had stable imaging. CONCLUSION: MRI-guided surgery results in improved resection imaging and real-time needle guidance in tumor operations. Its value could lie in low-grade lesions, where maximal resection is most beneficial. Copyright 2001 S. Karger AG, Basel

27
UI - 21363226
AU - Palu G; Bonaguro R; Gnatta E; Franchin E; Barzon L
TI - Gene therapy of brain and endocrine tumors.
SO - Croat Med J 2001 Aug;42(4):473-7
AD - Department of Histology, Microbiology, and Medical Biotechnologies, University of Padua, Italy. giorgio.palu@unipd.it
Gene therapy of cancer has become a major interest of medical research since more than 60% of the ongoing gene therapy protocols today involve cancer patients. To increase the therapeutic index of cancer gene therapy, targeting strategies have been developed to ensure that the expression of therapeutic genes is restricted exclusively to the tissue of interest. An attractive approach lies in the possibility to control the expression of therapeutic genes at the transcriptional level by the introduction of tissue-specific or tumor-specific enhancers/promoters offers. We have developed transcriptionally targeted vectors for gene therapy of solid tumors, including malignant gliomas and epithelial thyroid tumors. The choice of these tumor types relies on their clinical impact, ie, morbidity and mortality, the lack of effective conventional therapeutic strategies, and the ability of these tumors to express tissue/tumor-specific genes, whose transcriptional control elements (enhancer/promoter) may be used for achieving selective transgene expression. Here we report our clinical and preclinical experience in gene therapy of brain and thyroid tumors, and review the literature published on this topic.

28
UI - 21409311
AU - Matsumoto Y; Morisaki K; Miyake K; Kawanishi M; Kawai N; Ogawa T; Irie K; Kunishio K; Nagao S
TI - [Chemotherapy for gliomas based on the expression levels of drug resistant genes]
SO - No Shinkei Geka 2001 Jul;29(7):625-30
AD - Department of Neurological Surgery, Kagawa Medical University, 1750-1 Iketo, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
Drug resistance, which often occurs during chemotherapy, is still a great obstacle to the success of human malignancy treatment. Among many possible mechanisms of drug resistance (biological, biochemical, kinetic or pharmacological), both typical and atypical multidrug-resistance (MDR) have been extensively studied. We picked up MDR-1, MXR, MRP1, MRP2, TopoII alpha, MGMT, and GST-pi as drug-resistant gene, based on experimental data and previous reports. Expression of these genes were measured in 14 malignant glioma specimens by reverse transcription polymerase chain reaction assay. We chose anticancer drugs for each patient, based on results of drug resistant gene expression to acquire good response to drugs. Though our follow-up periods are not long enough to analyze the results of our chemotherapy, 78% (7/9) of our glioma patients who were treated with our chemotherapy are free from tumor progression. The assays, which measure the expression of drug resistant genes, are necessary to allow rapid detection of the drug-sensitivity to chemotherapy in malignant glioma patients.

29
UI - 21380389
AU - Wong GK; Poon WS; Lam MK
TI - The impact of an armless frameless neuronavigation system on routine brain tumour surgery: a prospective analysis of 51 cases.
SO - Minim Invasive Neurosurg 2001 Jun;44(2):99-103
AD - Division of Neurosurgery, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong.
A passive infrared armless and frameless neuronavigation system was introduced in routine intracranial and skull base surgery, and its impact on 51 cases in a one year period was assessed. No cases were rejected by the operating surgeon for lack of accuracy (