Richard Assaker

Temozolomide Treatment in Aggressive Pituitary Tumors and Pituitary Carcinomas: A French Multicenter Experience

CONTEXT To date only 18 patients with aggressive pituitary tumors or carcinomas treated with temozolomide have been reported. Increased expression of O6-methylguanine-DNA-methyltranferase (MGMT) has been suggested to predict resistance to temozolomide. OBJECTIVES The objective of the study was to describe the antitumoral efficacy and toxicity of temozolomide in patients with aggressive pituitary tumors or carcinomas and evaluate the possible prognostic value of MGMT promoter methylation and protein expression. PATIENTS Eight patients, five with pituitary carcinomas (three prolactin (PRL) and two ACTH) and three with aggressive pituitary tumors (one PRL and two ACTH), all treated with temozolomide administered orally for four to 24 cycles, were included in our French multicenter study. DESIGN MGMT expression was assessed by immunohistochemistry and MGMT promoter methylation by pyrosequencing. RESULTS Three of the eight patients (two ACTH adenomas and one PRL carcinoma) responded to temozolomide as demonstrated by significant tumor shrinkage and reduced hormone secretion. Three cycles of temozolomide were sufficient to identify treatment-responsive patients. Additional cycles did not improve treatment efficacy in those not responding, even when associated with carboplatin and vepeside. MGMT expression did not predict tumoral response to temozolomide because it was positive in one responder and negative in two nonresponders. Similarly, MGMT promoter methylation (three of seven tumors) did not predict clinical response. Toxicity remained mild in all patients. CONCLUSION Temozolomide treatment may be an effective option for some aggressive pituitary tumors or carcinomas. Response to a trial of three cycles of treatment seems sufficient to identify responders and more reliable than patient MGMT status.

Transpedicular Screw Placement: Image-guided versus Lateral-view Fluoroscopy: in Vitro Simulation

Study Design. In vitro evaluation of monitoring screw placement using an image-guided system compared with the routine use of an image intensifier. Objectives. To compare a new computer-guided method of monitoring pedicle screw placement with a well-known method of monitoring using an image intensifier, using measurements of screw placement time and accuracy. Summary of Background Data. Pedicle screw placement relies on the identification of anatomic landmarks for the point of entry of the pedicle. The direction and depth of screw penetration are guided by an intraoperative lateral-view image intensifier. The use of frameless stereotaxy for computer-aided pedicle screw placement may increase the accuracy and safety of the screw insertion. To the authors’ knowledge, there are no published data comparing these systems on the basis of operative time and screw placement accuracy. Method. Eight human cadaveric sections of five vertebrae each were used for an in vitro simulation of pedicle screw placement. Four spine surgeons were chosen to simulate the transpedicular screw placement. Each surgeon placed one screw into each pedicle of two spine sections (10 vertebrae, 20 screws). The surgeon was assisted by the lateral-view image intensifier on one spine section and by the navigational system on the second one. The four surgeons placed 80 pedicle screws. Forty screw placements were monitored by fluoroscopy and 40 by the image-guided navigational system. The time spent to place one screw was recorded, as well as the remarks by each surgeons on each method. Spines were rescanned, and the positions of the screws were compared between the group on which the image intensifier has been used and the group on which the navigational system had been used. Results. In the image-guided technique group, one thoracic screw disrupted the lateral cortex of the pedicle, the average distance to the anterior wall of the body was 5 mm, and the average time for the insertion of one screw was 13.5 minutes. In the other group, two screws disrupted the inner cortex of a thoracic pedicle, the average distance to the anterior wall was 10.7 mm, and the average time for the insertion of one screw was 4 minutes. Conclusions. In vitro computer-aided pedicle screw insertion is more accurate than lateral-view fluoroscopy in the thoracic spine. The main disadvantage is the time consumption compared with that required by lateral-view fluoroscopy. The total time of the surgical operation should be decreased with the future development of these techniques.

Diffusion tensor imaging and fibre tracking in cervical spondylotic myelopathy

ObjectivesTo (1) obtain microstructural parameters (Fractional Anisotropy: FA, Mean Diffusivity: MD) of the cervical spinal cord in patients suffering from cervical spondylotic myelopathy (CSM) using tractography, (2) to compare DTI parameters with the clinical assessment of these patients (3) and with information issued from conventional sequences.MethodsDTI was performed on 20 symptomatic patients with cervical spondylotic myelopathy, matched with 15 volunteers. FA and MD were calculated from tractography images at the C2-C3 level and compressed level in patients and at the C2-C3 and C4-C7 in controls. Patients were clinically evaluated using a self-administered questionnaire.ResultsThe FA values of patients were significantly lower at the compressed level than the FA of volunteers at the C4-C7 level. A significant positive correlation between FA at the compressed level and clinical assessment was demonstrated. Increased signal intensity on T2-weighted images did not correlate either with FA or MD values, or with any of the clinical scores.ConclusionFA values were significantly correlated with some of the patients’ clinical scores. High signal intensity of the spinal cord on T2 was not correlated either with the DTI parameters or with the clinical assessment, suggesting that FA is more sensitive than T2 imaging.

Local and sustained delivery of 5-fluorouracil from biodegradable microspheres for the radiosensitization of malignant glioma: a randomized phase II trial.

OBJECTIVE:This study was a randomized, multicenter Phase II trial comparing the effect of perioperative implantation of 5-fluorouracil-releasing microspheres followed by early radiotherapy (Arm A) and early radiotherapy alone (Arm B) in patients with gross total resection of high-grade glioma. METHODS:Patients were randomized on clinical and radiological assumption of supratentorial high-grade glioma. All patients underwent surgery, and after resection and histological confirmation, patients randomized to Arm A received multiple injections of microsphere suspension (130 mg of 5-fluorouracil). Conventional fractionated radiotherapy (59.4 Gy) was initiated between the second and the seventh day after surgery for both arms. RESULTS:A total of 95 patients were randomized. Seventy-seven patients were treated and analyzed in intention to treat for efficacy and safety. Overall survival was 15.2 months in Arm A and 13.5 months in Arm B. In the subpopulation of patients with complete resection, overall survival was 15.2 months in Arm A versus 12.3 months in Arm B. However, these differences were not significant. Safety was acceptable with prophylactic high doses of corticosteroids. CONCLUSION:It may be hypothesized that the implantation of 5-fluorouracil-loaded microspheres in the wall of the cavity resection did increase the overall survival, but the present study was not designed and sufficiently powered to demonstrate this.

Minimally invasive decompression and stabilization for the management of thoracolumbar spine metastasis

OBJECT Spinal metastasis with spinal cord involvement is a frequent complication in cancer patients. As the spinal compression frequently occurs ventrally, performing a simple posterior laminectomy alone is generally ineffective and dangerous. Many aggressive surgical strategies have been developed to improve outcomes for patients with metastatic spine disease. These strategies are associated with high morbidity and complication rates, especially in patients with numerous neoplasm-associated comorbidities, which can limit their indication in patients with a limited life expectancy. The authors performed a prospective evaluation of minimally invasive decompression and stabilization for the palliative management of symptomatic thoracolumbar spine metastasis. METHODS Ten patients with metastasis to the thoracolumbar spine and neurological compromise underwent minimally invasive transpedicular vertebrectomy and spinal cord decompression through a tubular expandable retractor. Percutaneous stabilization was also systematically performed to ensure spinal stability. RESULTS No complications during the procedure were reported. The mean operative duration was 170 minutes and the mean estimated blood loss was 400 ml. The postoperative course of all patients was uneventful, with the exception of 1 benign urinary tract infection. Eight patients (80%) improved at least 1 Frankel grade. CONCLUSIONS Minimally invasive treatment of thoracolumbar spine metastasis is a safe and effective palliative option in patients with limited life expectancy, to limit morbidity and preserve quality of life.

Intraventricular Cavernomas: Three Cases and Review of the Literature

OBJECTIVE AND IMPORTANCE Cavernomas occur very rarely in the ventricular system. We report three cases of intraventricular cavernomas and review the literature. CLINICAL PRESENTATION A 16-year-old female patient presented with a sudden distal deficit of the left superior limb. She had a voluminous tumor involving the two lateral ventricles, with radiological evidence of recent hemorrhage. A 30-year-old man presented with generalized seizures and a right hemiplegia related to a 4-cm-diameter cavernoma in the two lateral ventricles involving the interhemispheric scissure through the corpus callosum and left centrum ovale. The radiological appearance was not typical and did not allow the diagnosis. A 42-year-old man had a cavernoma in the third ventricle, which was responsible for his short-term memory loss. This cavernoma had been revealed by computed tomography that was performed after intracerebral hemorrhage related to another cavernoma in the right parietal lobe occurred. INTERVENTION Stereotactic biopsies allowed the diagnosis of intraventricular cavernoma in the first case. Surgical removal via a right transcortical transventricular approach and a transcallosal approach in the first and second cases, respectively, was complete, resulting in good outcomes. Surgical removal via a right transcortical transventricular approach in the third case was partial. CONCLUSION Intraventricular cavernomas are so uncommon that only 42 well-documented cases have been previously reported in the literature. It seems that their radiological diagnosis may be difficult because of their uncommon location in the ventricular system and their voluminous size. A wrong preoperative diagnosis has sometimes been the cause of inefficient therapy, such as radiotherapy, for these surgically curable benign lesions.

Foramen Magnum Syndrome Secondary to Calcium Pyrophosphate Crystal Deposition in the Transverse Ligament of the Atlas

Study Design. This report illustrates two rare cases of foramen magnum syndrome caused by a retro-odontoid mass in which calcium pyrophosphate dihydrate crystals were found. Objectives. To analyze the preoperative studies and the diagnostic criteria and to discuss the surgical treatment. The present cases will be compared with previous ones described in the literature. Summary of Background Data. Deposition of calcium pyrophosphate dihydrate crystals occurs into the fibrous and hyaline cartilage of the joints and intervertebral discs of the spine. Half of the patients known to have a chondrocalcinosis had asymptomatic calcification in the odontoid region. Ten patients were published in the literature as having a spinal cord syndrome secondary to calcium pyrophosphate dihydrate deposition in the odontoid region. Methods. In both cases the preoperative studies were analyzed, and the retro-odontoid mass was resected and histologically examined. Both had an anterior transoral approach and have been followed for 1 year. Results. According to the preoperative radiographs the diagnosis was suspected and confirmed histologically. Transoral approach was done with no need in either case for a posterior stabilization. Conclusions. Compression of the spinal cord by calcium pyrophosphate dihydrate deposition may occur. The preoperative diagnosis may be highly suspected after radiographic study and histologically confirmed. Transoral resection is the treatment of choice. Posterior stabilization should be considered only in cases of craniovertebral instability.

Pronostic factors of synchronous brain metastases from lung cancer

BACKGROUND The prognosis of brain metastases (BM) from lung cancer is poor. The management of lung cancer with BM is not clear. This retrospective study attempts to determine their prognostic factors, and to better define the role of different treatments. METHODS We reviewed the clinical characteristics of 271 consecutive patients with synchronous brain metastases (SBM) from lung cancer (small-cell lung cancers and non-small-cell lung cancers), collected between January 1985 and May 1993. Data were available for all patients as well as follow-up information on all patients through to death. Patients had all undergone heterogeneous treatments. Each physician had chosen the appropriate treatment after collegiate discussion. Survival curves were compared using the log-rank test in univariate analysis, and Coxs Regression model in multivariate analysis. Statistical significance was defined as P<0.05. RESULTS 249 patients were assessable. Treatments included: neurosurgical resection in 56 cases, brain irradiation in 87 cases, and chemotherapy in 126 cases. Median overall survival time from the date of histological diagnosis of SBM was 103 days (range, 1-1699). In multivariate analysis, prognostic factors for longer overall survival times were: absence of adrenal metastases (P=0.007), neurosurgical resection (P=0.028), chemotherapy (P=0.032) and brain irradiation (P=0.008). Moreover, risk factors of intracranial hypertension as cause of death were number of SBM and absence of neurosurgical resection. CONCLUSIONS These results and others suggest that patients with SBM from lung cancer be considered for carcinologic treatment, and not only for best supportive care. However, further studies are necessary to evaluate quality of life with or without carcinologic treatment.

Intradural epidermoid cysts of the cerebellopontine angle: diagnosis and surgery.

ABSTRACT: WE REPORT ON our recent experience with epidermoid cysts in the cerebellopontine angle. We operated on nine patients since 1985, seven of which were investigated with magnetic resonance imaging. Since the arrival of modern neuroimaging, large lesions can be found with only discrete symptoms, such as isolated tinnitus or unspecific headache. With computed tomography and magnetic resonance imaging, preoperative diagnosis was achieved for most patients; sometimes, however, epidermoid cysts may be very similar to arachnoid cysts. Surgery is the only possible treatment. The decision to operate should be carefully discussed for each patient, particularly if the patient is asymptomatic. The extent of the lesion at the anterior aspect of the brain stem, and sometimes above the tentorium cerebelli, fragile cortex, and vessels, and hazards of postoperative chemical meningitis often make such surgery difficult. The surgeon should not attempt total removal of the cyst membrane. Most patients who undergo surgery, however, recover well, with no or few sequelae. With a mean 3‐year follow‐up, no recurrence occurred, despite partial removal, as a result of the peculiarly slow growth of these lesions.

Endothelial Expression of Endocan Is Strongly Associated with Tumor Progression in Pituitary Adenoma

Although benign, pituitary adenomas frequently invade adjacent sinuses or recur after first surgery. To date, there is no histological marker predictive of recurrence. Angiogenic factors are candidate markers. Endocan is a proteoglycan secreted by endothelial cells, associated with an aggressive behavior in several tumor types. Endocan expression was investigated by immunohistochemistry and reverse transcription polymerase chain reaction (RT‐PCR) in 18 normal post‐mortem pituitaries and in 107 patients operated for a pituitary adenoma (with a follow‐up of at least 8 years after surgery). In normal pituitaries, endocan was never observed in vessels but was detected in isolated endocrine cells. In adenoma tissue, we found a strong association between endocan immunoreactivity in endothelial cells and progression (P = 0.0009), as well as tumor size (P = 0.0012), raised mitotic count (P = 0.02) and p53 expression (P = 0.032). Morphometric analysis of the microvessels showed that the mean vessel area was significantly higher in the subgroup of tumors with an endothelial expression of endocan (P = 0.028), coherent with the neoangiogenesis process occurring in the pituitary. The immunolabeling of endocan in endothelial cells may therefore appear to be a relevant marker of aggressive behavior in pituitary tumors.