Paclitaxel poliglumex, temozolomide, and radiation for newly diagnosed high-grade glioma: a Brown University Oncology Group Study.

OBJECTIVES: Paclitaxel poliglumex (PPX), a drug conjugate that links paclitaxel to poly-L-glutamic acid, is a potent radiation sensitizer. Prior studies in esophageal cancer have demonstrated that PPX (50 mg/m/wk) can be administered with concurrent radiation with acceptable toxicity. The primary objective of this study was to determine the safety of the combination of PPX with temozolomide and concurrent radiation for high-grade gliomas. METHODS: Eligible patients were required to have WHO grade 3 or 4 gliomas. Patients received weekly PPX (50 mg/m/wk) combined with standard daily temozolomide (75 mg/m) for 6 weeks with concomitant radiation (2.0 Gy, 5 d/wk for a total dose of 60 Gy). RESULTS: Twenty-five patients were enrolled, 17 with glioblastoma and 8 with grade 3 gliomas. Seven of 25 patients had grade 4 myelosuppression. Hematologic toxicity lasted up to 5 months suggesting a drug interaction between PPX and temozolomide. For patients with glioblastoma, the median progression-free survival was 11.5 months and the median overall survival was 18 months. CONCLUSIONS: PPX could not be safely combined with temozolomide due to grade 4 hematologic toxicity. However, the favorable progression-free and overall survival suggest that PPX may enhance radiation for glioblastoma. A randomized study of single agent PPX/radiation versus temozolomide/radiation for glioblastoma without MGMT methylation is underway.

The safety and feasibility of outpatient carotid endarterectomy.

BACKGROUND: Carotid endarterectomy (CEA) is one of the most commonly performed and studied surgical procedures for extracranial ischemic disease. OBJECTIVE: The authors reviewed the outcome of 39 consecutive carotid endarterectomy procedures performed by a single surgeon with emphasis on the safety of discharging patients the same day of the procedure. METHODS: Retrospective analysis was performed over a two-year period on patients who were admitted as outpatients and underwent CEA. Following CEA, patients were observed for 4-6h in the recovery room and Duplex ultrasonography was completed to assess the endarterectomy repair. Determination was then made whether patients could be safely discharged home. RESULTS: Over a two year period, CEA was performed 39 times in 37 outpatients. Twenty-five patients (64%) were discharged within 6h of surgery completion. The remaining 14 patients (36%) were admitted to the hospital for varying reasons. Six patients (43%) stayed either due to personal preference or the lack of supervision at home and six other patients (43%) stayed because of mild hemodynamic instability. Of the two remaining patients, one was admitted for chest pain and the other for a small wound hematoma. No patients developed postoperative neurologic deficits. Two-tailed Fisher test analysis of collected variables revealed that patients who had general anesthesia were more likely to be admitted (p<0.02). CONCLUSION: Patients undergoing CEA can be safely discharged the same day after a brief period of postoperative observation. One factor that may predict the need for postoperative admission is the use of general anesthesia.

Transsphenoidal resection of sellar tumors using high-field intraoperative magnetic resonance imaging.

There has been increasing experience in the utilization of intraoperative magnetic resonance imaging (iMRI) for intracranial surgery. Despite this trend, only a few U.S centers have examined the use of this technology for transsphenoidal resection of tumors of the sella. We present the largest series in North America examining the role of iMRI for pituitary adenoma resection. We retrospectively reviewed our institutional experience of 59-patients who underwent transsphenoidal procedures for sellar and suprasellar tumors with iMRI guidance. Of these, 52 patients had a histological diagnosis of pituitary adenoma. The technical results of this subgroup were examined. A 1.5-T iMRI was integrated with the BrainLAB (Feldkirchen, Germany) neuronavigation system. The majority (94%) of tumors in our series were macroadenomas. Seventeen percent of tumors were confined to the sella, 49% had suprasellar extensions without involvement of the cavernous sinus, 34% had frank cavernous sinus invasion. All patients underwent at least one iMRI, and 19% required one or more additional sets of intraoperative imaging. In 58% of patients, iMRI led to the surgeon attempting more resection. A gross total resection was obtained in 67% of the patients with planned total resections. There was one case of permanent postoperative diabetes insipidus and no other instances of new hormone replacement. In summary, iMRI was most useful for tumors of the sella with and without suprasellar extension where the information from the iMRI extended the complete resection rate from 40 to 72% and 55 to 88%, respectively. As one would expect, it did not substantially increase the rate of resection of tumors with cavernous sinus invasion. Overall, iMRI was particularly useful in guiding resection safely, aiding in clinical decision making, and allowing identification and preservation of the pituitary stalk and normal pituitary gland. Limitations of the iMRI include a need for additional personnel and training as well as additional operative time, which diminishes over time as personnel learn to optimize workflow efficiency. Additional costs are mitigated in part by using the iMRI as an immediate postoperative scan. Other data emerging from our experience suggest that preservation of normal gland and thus avoidance of hypopituitarism may be improved by iMRI use, but longer follow-up periods are required to test this conclusion. iMRI can detect unsuspected complications sooner than routine postoperative imaging, potentially leading to improved outcomes. However, larger studies are needed.

Preoperative MRI evaluation of pituitary macroadenoma: imaging features predictive of successful transsphenoidal surgery.

OBJECTIVE: The purpose of this study was to determine whether the preoperative MRI findings of enhanced diffusivity, macrocyst content, and internal hemorrhage in pituitary macroadenomas are predictive of successful transsphenoidal hypophysectomy. MATERIALS AND METHODS: We retrospectively reviewed the preoperative and postoperative sella protocol MR images of 28 patients who underwent transsphenoidal hypophysectomy for chiasm-compressing macroadenoma. Chiasmatic decompression defined surgical success. Two neuroradiologists differentiated nonsolid (macrocystic and macrohemorrhagic) from solid tumors, computed apparent diffusion coefficient (ADC) and T2-weighted signal intensity normalized to pons in solid tumors, and measured change in tumor height. A neuropathologist graded reticulin content in tumor specimens. Categorical and dichotomous variables were examined with the chi-square or Fisher's exact test; continuous-scale data were analyzed with the Student's t test, analysis of variance, or linear regression. RESULTS: Transsphenoidal hypophysectomy succeeded in the management of 10 of 11 nonsolid tumors and nine of 17 solid tumors (p = 0.049). The ratios of tumor to brainstem ADC in the nine successfully resected solid tumors were higher than in the eight cases of failed treatment (p = 0.008) with no significant difference in ratio of tumor to brainstem T2-weighted signal intensity (p = 0.76). All six solid tumors with enhanced diffusivity (ratio of tumor to brainstem ADC > 1.1) were successfully managed with transsphenoidal hypophysectomy, compared with three of 11 with an ADC ratio less than 1.1 (p = 0.009). There was a significant main effect of ADC ratio groupings on change in tumor height (p = 0.02), and a linear relation was found between ADC ratio and change in tumor height (p = 0.04). Taken together, tumors with nonsolid features or an ADC ratio greater than 1.1 were highly resectable (p < 0.001; sensitivity, 0.84; specificity, 0.89). ADC ratios in reticulin-poor solid tumors were higher than those in reticulin-rich tumors (p = 0.024). CONCLUSION: Macrocystic and macrohemorrhagic adenomas and solid tumors with enhanced diffusivity are more likely to be successfully managed with transsphenoidal hypophysectomy. Transsphenoidal hypophysectomy of solid, enhancing tumors with restricted diffusion is more likely to fail, possibly because of the greater reticulin content of the tumor; initial transcranial surgery may be appropriate in these cases.

Endonasal ethmoidectomy and bifrontal craniotomy with craniofacial approach for resection of frontoethmoidal osteoma causing tension pneumocephalus.

Tension pneumocephalus is an unusual, potentially life-threatening complication of frontal fossa tumors. We present an uncommon case of a frontoethmoidal osteoma causing a tension pneumocephalus and neurological deterioration prompting a combined endonasal ethmoidectomy and bifrontal craniotomy with craniofacial approach for resection. A 68-year-old man presented with a 1-week history of worsening headache, slowness of speech, and increasing confusion. Standard computed tomography scan revealed a marked tension pneumocephalus with ventricular air and 1-cm midline shift to the right. Further studies showed a calcified left ethmoid mass and a left anterior cranial-base defect. A team composed of neurosurgery and otolaryngology performed a combined endonasal ethmoidectomy and bifrontal craniotomy with craniofacial approach to resect a large frontoethmoid bony tumor. No abscess or mucocele was identified. The skull base defect was repaired with the aid of a transnasal endoscopy, a titanium mesh, and a pedunculated pericranial flap. Postoperatively, the pneumocephalus and the patient's symptoms completely resolved. Pathology was consistent with a benign osteoma. This is an uncommon case of a frontoethmoidal osteoma associated with tension pneumocephalus. Recognition of this entity and timely diagnosis and treatment, consisting of an endonasal ethmoidectomy and a bifrontal craniotomy with craniofacial approach, may prevent potential life-threatening complications.

Stereotactic radiosurgery for functional disorders.

Stereotactic radiosurgery (SRS) with the Gamma Knife and linear accelerator has revolutionized neurosurgery over the past 20 years. The most common indications for radiosurgery today are tumors and arteriovenous malformations of the brain. Functional indications such as treatment of movement disorders or intractable pain only contribute a small percentage of treated patients. Although SRS is the only noninvasive form of treatment for functional disorders, it also has some limitations: neurophysiological confirmation of the target structure is not possible, and one therefore must rely exclusively on anatomical targeting. Furthermore, lesion sizes may vary, and shielding adjacent radiosensitive neural structures may be difficult or impossible. The most common indication for functional SRS is the treatment of trigeminal neuralgia. Radiosurgical treatment for epilepsy and certain psychiatric illnesses is performed in several centers as part of strict research protocols, and radiosurgical pallidotomy or medial thalamotomy is no longer recommended due to the high risk of complications. Radiosurgical ventrolateral thalamotomy for the treatment of tremor in patients with Parkinson disease or multiple sclerosis, as well as in the treatment of essential tremor, may be indicated for a select group of patients with advanced age, significant medical conditions that preclude treatment with open surgery, or patients who must receive anticoagulation therapy. A promising new application of SRS is high-dose radiosurgery delivered to the pituitary stalk. This treatment has already been successfully performed in several centers around the world to treat severe pain in patients with end-stage cancer.

Neuroanatomical localization of the 'precentral knob' with computed tomography imaging.

BACKGROUND/AIMS: The 'precentral knob', a cortical representation of the motor hand function, can be identified and localized consistently using magnetic resonance imaging (MRI) and functional MRI. We present a method of indirectly identifying and localizing the Omega-shaped precentral knob using the anatomical landmarks on computed tomography (CT). METHODS: CT and MRI obtained within 24 h from 10 patients undergoing a headache workup and found to be negative for any anatomical abnormalities were studied. First, the precentral knob was identified in the CT images. Then, the 'coronal suture line' and 'midline' were identified and used to measure the distance to the precentral knob on both hemispheres. MRI was used to confirm the location of the precentral knob in the CT images based on anatomical landmarks (i.e. sulcal configurations). RESULTS: The precentral knob is located 45.1 +/- 5.2 mm posterior with respect to the coronal suture line and 33.9 +/- 3.4 mm lateral to the midline on the right hemisphere, and 44.6 +/- 5.7 mm posterior and 33.2 +/- 2.5 mm lateral on the left hemisphere. CONCLUSION: We present a method of consistently identifying and localizing the Omega-shaped precentral knob, a cortical representation of the motor hand function, using CT.

Utility of apparent diffusion coefficient in predicting the outcome of Gamma Knife-treated brain metastases prior to changes in tumor volume: a preliminary study.

OBJECT: Gamma Knife surgery (GKS) is often the sole treatment for brain metastases. The authors hypothesized that early post-GKS measures of the relative apparent diffusion coefficient (rADC) could predict therapeutic response, recurrence, and radionecrosis prior to changes in tumor volume. METHODS: Magnetic resonance (MR) images of 25 metastatic tumors in 15 patients were reviewed. Inclusion criteria included a history of surgery or GKS, a minimum tumor diameter of 5 mm at treatment, and a minimum of two follow-up MR images. Tumor volumes were normalized to baseline, and tumor ADC values were normalized to normal-appearing white matter (rADC). A successful therapeutic response (STR) was defined by a monotonically decreasing tumor volume throughout the follow-up period. Magnetic resonance spectroscopy was used to classify non-STRs as radionecrosis or tumor recurrence. All tumors exhibited a decreased normalized volume (mean 37%) at the first follow-up examination (range 33-124 days after GKS, mean 54 days), and three distinct rADC patterns subsequently evolved: Group 1 (STR [10 cases]), monotonically decreasing volume with gradually increasing rADC; Group 2 (radionecrosis [three cases]), initial volume reduction followed by gradual increase, with initial rapidly increasing rADC followed by more gradual increase or plateau; and Group 3 (recurrent tumor [12 cases]), initial volume decrease followed by increase, with a preceding gradual decrease in the rADC. CONCLUSIONS: The rADC patterns outperform initial post-GKS tumor volume in predicting the long-term response to treatment. Decreasing tumor volume with an increasing rADC predicts an STR. For lesions with increasing volume, antecedent rADC reduction predicts recurrence, whereas a rapidly increasing rADC predicts radionecrosis. Evaluation of the rADC at the initial post-GKS follow-up examination appears to be a useful prognostic measure of metastatic tumor response.