John George Golfinos, M.D.

Local Control of Newly Diagnosed and Distally Recurrent, Low-Volume Brain Metastases Using Fixed Dose (20 Gy) Gamma Knife Radiosurgery
Elliott RE; Rush SC; Morsi A; Mehta N; Spriet J; Narayana A; Donahue B; Parker EC; Golfinos JG
2011 Apr;68(4):921-931, Neurosurgery
BACKGROUND:: Metastases to the brain occur in 20-30% of patients with cancer and have been identified on autopsy in as many as 50% of patients. OBJECTIVE:: To analyze the efficacy of 20 Gy gamma knife radiosurgery (GKR) as initial treatment in patients with 1 to 3 brain metastases </= 2 cm in greatest diameter. METHODS:: A retrospective analysis of 114 consecutive adults with KPS >/= 60 who received GKR for 1 to 3 brain metastases </= 2 cm in size was performed. Five patients lacked detailed follow-up and were excluded, leaving 109 for outcome analysis (34 males/75 females; median age: 61.2 years). All metastases received 20 Gy to the 50%-isodose line. RESULTS:: One hundred-nine patients underwent treatment of 164 metastases at initial GKR. Twenty-six patients (23.9%) were alive at last follow-up (median time: 29.9 months; range: 6.6 months to 7.8 years). The median overall survival was 13.8 months (range: 1 day to 7.6 years). Among the 52 patients with distant failure, 33 patients received 20 Gy to 95 new lesions. A total of 259 metastases received 20 Gy and 4 patients lacked imaging follow-up secondary to death prior to post-treatment imaging. Local failure occurred in 17 of 255 treated lesions (6.7%), yielding an overall local control rate of 93.3%. Actuarial local control at 6-, 12-, 24-, and 36-months was 96%, 93%, 89%, and 88%, respectively. Permanent neurological complications occurred in 3 patients (2.8%). CONCLUSION:: Among patients with 1 to 3 brain metastases </= 2 cm in size who have not received whole-brain radiation therapy, GKR with 20 Gy provides high rates of local control with low morbidity and excellent neurological symptom-free survival
— id: 124087, year: 2011, vol: 68, page: 921, stat: Journal Article,

Efficacy of gamma knife radiosurgery for small-volume recurrent malignant gliomas after initial radical resection
Elliott, Robert E; Parker, Erik C; Rush, Stephen C; Kalhorn, Stephen P; Moshel, Yaron A; Narayana, Ashwatha; Donahue, Bernadine; Golfinos, John G
2011 Jul-Aug;76(1-2):128-140, World neurosurgery
OBJECTIVE: To review the authors' experience with Gamma Knife radiosurgery (GKR) for small recurrent high-grade gliomas (HGGs) following prior radical resection, external-beam radiation therapy (EBRT), and chemotherapy with temozolomide (TMZ). METHODS: The authors retrospectively analyzed 26 consecutive adults (9 women and 17 men; median age 60.4 years; Karnofsky Performance Status [KPS] >/=70) who underwent GKR for recurrent HGGs from 2004-2009. Median lesion volume was 1.22 cc, and median treatment dose was 15 Gy. Pathology included glioblastoma multiforme (GBM; n = 16), anaplastic astrocytoma (AA; n = 5), and anaplastic mixed oligoastrocytoma (AMOA; n = 5). Two patients lost to follow-up were excluded from radiographic outcome analyses. RESULTS: Median overall survival (OS) for the entire cohort from the time of GKR was 13.5 months. Values for 12-month actuarial survival from time of GKR for GBM, AMOA, and AA were 37%, 20% and 80%. Local failure occurred in 9 patients (37.5%) at a median time of 5.8 months, and 18 patients (75%) experienced distant progression at a median of 4.8 months. Complications included radiation necrosis in two patients and transient worsening of hemiparesis in one patient. Multivariate hazard ratio (HR) analysis showed KPS 90 or greater, smaller tumor volumes, and increased time to recurrence after resection to be associated with longer OS following GKR. CONCLUSIONS: GKR provided good local tumor control in this group of clinically stable and predominantly high-functioning patients with small recurrent HGGs after radical resection. Meaningful survival times after GKR were seen. GKR can be considered for selected patients with recurrent HGGs
— id: 136644, year: 2011, vol: 76, page: 128, stat: Journal Article,

Invasion is not an independent prognostic factor in high-grade glioma
Narayana, Ashwatha; Perretta, Donato; Kunnakkat, Saroj; Gruber, Deborah; Golfinos, John; Parker, Erik; Medabalmi, Praveen; Zagzag, David; Pat Eagan, R N; Gruber, Michael
2011 Jul;7(3):331-335, Journal of cancer research & therapeutics
Purpose: The role of invasion as a prognostic factor in high-grade gliomas (HGG) remains controversial. An apparent increase in invasiveness following anti-angiogenic therapy makes this question clinically relevant. The goal of this study is to assess survival differences in patients with newly diagnosed HGG who present with diffuse invasive disease compared to those who did not, but went on to develop diffuse invasive disease following bevacizumab therapy. Materials and Methods: Twenty-three patients presented as newly diagnosed diffuse invasive HGG. All patients underwent surgical resection with radiation therapy and temozolomide for one year. Progression-free survival (PFS) and overall survival (OS) were compared to a control of 58 patients with focal high-grade glioma who received similar therapy, but that included bevacizumab at 10 mg/kg given every two weeks. Results: The patient characteristics were similar in each group. The median PFS and OS for invasive HGG patients were 6 and 13 months and for the focal HGG patients, 11 and 24 months, respectively (P=0.092 and P=0.071). In the subgroup of invasive HGG that showed significant angiogenesis, the median PFS and OS were 3 and 9 months, respectively. 56% of the focal HGG patients recurred as diffuse invasive relapse. For patients with focal HGG who recurred as invasive disease, the median PFS and OS were 9 and 21 months respectively. Conclusions: Presence of diffuse invasive disease not accompanied by angiogenesis either prior to therapy or subsequent to anti-angiogenic therapy does not seem to have prognostic significance. However, invasion accompanied by angiogenesis in newly diagnosed HGG may confer a poor prognosis
— id: 140539, year: 2011, vol: 7, page: 331, stat: Journal Article,

Auditory rehabilitation of patients with neurofibromatosis Type 2 by using cochlear implants
Roehm, Pamela C; Mallen-St Clair, Jon; Jethanamest, Daniel; Golfinos, John G; Shapiro, William; Waltzman, Susan; Roland, J Thomas Jr
2011 Oct;115(4):827-834, Journal of neurosurgery
OBJECT: The aim of this study was to determine whether patients with neurofibromatosis Type 2 (NF2) who have intact ipsilateral cochlear nerves can have open-set speech discrimination following cochlear implantation. METHODS: Records of 7 patients with documented NF2 were reviewed to determine speech discrimination outcomes following cochlear implantation. Outcomes were measured using consonant-nucleus-consonant words and phonemes; Hearing in Noise Test sentences in quiet; and City University of New York sentences in quiet and in noise. RESULTS: Preoperatively, none of the patients had open-set speech discrimination. Five of the 7 patients had previously undergone excision of ipsilateral vestibular schwannoma (VS). One of the patients who received a cochlear implant had received radiation therapy for ipsilateral VS, and another was undergoing observation for a small ipsilateral VS. Following cochlear implantation, 4 of 7 patients with NF2 had open-set speech discrimination following cochlear implantation during extended follow-up (15-120 months). Two of the 3 patients without open-set speech understanding had a prolonged period between ipsilateral VS resection and cochlear implantation (120 and 132 months), and had cochlear ossification at the time of implantation. The other patient without open-set speech understanding had good contralateral hearing at the time of cochlear implantation. Despite these findings, 6 of the 7 patients were daily users of their cochlear implants, and the seventh is an occasional user, indicating that all of the patients subjectively gained some benefit from their implants. CONCLUSIONS: Cochlear implantation can provide long-term auditory rehabilitation, with open-set speech discrimination for patients with NF2 who have intact ipsilateral cochlear nerves. Factors that can affect implant performance include the following: 1) a prolonged time between VS resection and implantation; and 2) cochlear ossification
— id: 141067, year: 2011, vol: 115, page: 827, stat: Journal Article,

Incidence, timing, and treatment of new brain metastases after Gamma Knife surgery for limited brain disease: the case for reducing the use of whole-brain radiation therapy
Rush, Stephen; Elliott, Robert E; Morsi, Amr; Mehta, Nisha; Spriet, Jeri; Narayana, Ashwatha; Donahue, Bernadine; Parker, Erik C; Golfinos, John G
2011 Jul;115(1):37-48, Journal of neurosurgery
OBJECT: In this paper, the authors' goal was to analyze the incidence, timing, and treatment of new metastases following initial treatment with 20-Gy Gamma Knife surgery (GKS) alone in patients with limited brain metastases without whole-brain radiation therapy (WBRT). METHODS: A retrospective analysis of 114 consecutive adults (75 women and 34 men; median age 61 years) with KPS scores of 60 or higher who received GKS for 1-3 brain metastases </= 2 cm was performed (median lesion volume 0.35 cm(3)). Five patients lacking follow-up data were excluded from analysis. After treatment, patients underwent MR imaging at 6 weeks and every 3 months thereafter. New metastases were preferentially treated with additional GKS. Indications for WBRT included development of numerous metastases, leptomeningeal disease, or diffuse surgical-site recurrence. RESULTS: The median overall survival from GKS was 13.8 months. Excluding the 3 patients who died before follow-up imaging, 12 patients (11.3%) experienced local failure at a median of 7.4 months. Fifty-three patients (50%) developed new metastases at a median of 5 months. Six (7%) of 86 instances of new lesions were symptomatic. Most patients (67%) with distant failures were successfully treated using salvage GKS alone. Whole-brain radiotherapy was indicated in 20 patients (18.3%). Thirteen patients (11.9%) died of neurological disease. CONCLUSIONS: For patients with limited brain metastases and functional independence, 20-Gy GKS provides excellent disease control and high-functioning survival with minimal morbidity. New metastases developed in almost 50% of patients, but additional GKS was extremely effective in controlling disease. Using our algorithm, fewer than 20% of patients required WBRT, and only 12% died of progressive intracranial disease
— id: 136631, year: 2011, vol: 115, page: 37, stat: Journal Article,

R132H-mutation of isocitrate dehydrogenase-1 is not sufficient for HIF-1alpha upregulation in adult glioma
Williams, Susan C; Karajannis, Matthias A; Chiriboga, Luis; Golfinos, John G; von Deimling, Andreas; Zagzag, David
2011 Feb;121(2):279-281, Acta neuropathologica
— id: 138149, year: 2011, vol: 121, page: 279, stat: Journal Article,

Efficacy of Clevidipine in Controlling Perioperative Hypertension in Neurosurgical Patients: Initial Single-center Experience
Bekker, Alex; Didehvar, Sorosch; Kim, Sunmi; Golfinos, John G; Parker, Erik; Sapson, Andrew; Haile, Michael; Kline, Richard; Lee, Mitchell
2010 Oct;22(4):330-335, Journal of neurosurgical anesthesiology
BACKGROUND: Acute blood pressure (BP) elevations in neurosurgical patients are associated with serious neurologic, cardiovascular, or surgical site complications. Clevidipine, an ultra-short-acting dihydropyridine calcium antagonist, has been shown to be efficacious and safe for acute hypertension in cardiac surgery. This study assessed the efficacy and safety of clevidipine in controlling perioperative hypertension in the neurosurgical setting. METHODS: Patients scheduled for intracranial surgery were prospectively enrolled after giving consent. Clevidipine (0.5 mg/mL in 20% lipid solution, which was to be initiated at 10 mg/h and titrated to effect) was administered as the primary antihypertensive agent for perioperative hypertension, with target BPs of less than 130 mm Hg. Other vasoactive drugs were administered as needed for treating systolic BP (SBP) less than 90 mm Hg or greater than 130 mm Hg. The primary study endpoint was the proportion of patients not requiring rescue antihypertensives to maintain target SBP (<130 mm Hg). RESULTS: Twenty-two patients were enrolled. One patient did not require antihypertensive therapy. Seventeen patients (17 of 21, 81%) were treated with clevidipine alone; one received clevidipine in the postanesthesia care unit only. Twenty-eight hypertensive episodes (defined as any new acute BP elevation requiring clevidipine initiation) were documented. SBP was reduced to target level within 15 minutes in 22 of 28 episodes (78.6%). Two mild hypotensive episodes occurred after the initiation of clevidipine infusion; these transient decreases in BP were treated with vasoactive drugs and resolved within 5 minutes. CONCLUSIONS: Clevidipine is effective and safe for perioperative hypertension in patients undergoing intracranial procedures. Rapid control of BP is possible with higher starting doses. Drug effects resolved rapidly after drug discontinuation
— id: 112425, year: 2010, vol: 22, page: 330, stat: Journal Article,

Neurological complications and symptom resolution following Gamma Knife surgery for brain metastases 2 cm or smaller in relation to eloquent cortices
Elliott, Robert E; Rush, Stephen; Morsi, Amr; Mehta, Nisha; Spriet, Jeri; Narayana, Ashwatha; Donahue, Bernadine; Parker, Erik C; Golfinos, John G
2010 Dec;113 Suppl:53-64, Journal of neurosurgery
OBJECT: Reports on resection of tumors in or near eloquent cortices have noted neurological complications in up to 30% of patients. This paper contains an analysis of symptom resolution and neurological morbidity following 20-Gy Gamma Knife surgery (GKS) for supratentorial brain metastases < or = 2 cm in greatest diameter. METHODS: The authors performed a retrospective analysis of 98 consecutively treated adults (33 men and 65 women with a median age of 61.4 years at the time of GKS) with Karnofsky Performance Scale score > or = 60, who underwent GKS for supratentorial brain metastases < or = 2 cm in diameter. Lesion location was classified as noneloquent (Grade I), near eloquent (Grade II), or eloquent (Grade III), in accordance with the grading system developed by the group at M. D. Anderson Cancer Center. Following treatment, the patients underwent MR imaging and clinical examinations at 6 weeks and every 3 months thereafter. RESULTS: Ninety-eight patients underwent 20-Gy GKS for 131 metastases at initial presentation and 31 patients underwent salvage 20-Gy GKS for 76 new lesions, for a total of 207 lesions (mean lesion volume 0.44 cm3). Lesions were classified as follows: Grade I, 96 (46.4%); Grade II, 51 (24.6%); and Grade III, 60 (29%). Fifteen patients (2 with Grade II and 13 with Grade III lesions) presented with deficits referable to their lesions, yielding pre-GKS deficit rates of 7.2% per lesion and 15.3% per patient. The pre-GKS deficits improved or resolved in 10 patients (66.7%) at a median time of 2.8 months and remained stable in 3 patients (20%). Two patients (13.3%) experienced worsened neurological deficits. One patient who was neurologically intact prior to treatment developed a new hemiparesis (1 of 83 patients [1.2%]). The rates of permanent neurological deterioration following GKS for Grades I, II, and III lesions were 0% (0 of 96 tumors), 2% (1 of 51), and 3.3% (2 of 60), respectively. The pre-GKS neurological deficits and larger lesions were the most significant risk factors for post-GKS neurological deterioration. CONCLUSIONS: Gamma Knife surgery performed using a 20-Gy dose provides amelioration of neurological deficits from brain metastases that are < or = 2 cm in diameter and located in or near eloquent cortices in nearly two-thirds of patients with a low incidence of morbidity. Consistent with the surgical literature, higher rates of neurological complications were observed as proximity to eloquent regions and lesion size increased. There was no neurological deterioration in patients harboring metastases in noneloquent areas
— id: 119235, year: 2010, vol: 113 Suppl, page: 53, stat: Journal Article,

Phase II clinical trial of lapatinib in children and adults with NF2-related tumors
Karajannis M.A.; Ballas M.; Ayanru I.; Orrico A.; Nusbaum A.; Hagiwara M.; Roland T.; Golfinos J.; Allen J.
2010 ;12(6):ii43-ii43, Neuro-oncology
PURPOSE: Lapatinib is an orally active receptor tyrosine kinase inhibitor that reversibly inhibits EGFR and ErbB2. We have recently shown that EGFR and ErbB2 are consistently expressed and activated in vestibular schwannomas (VS) in patients with NF2 and that lapatinib is active in a preclinical VS model. This study aims to determine the response rate to lapatinib in children and adults with VS and other NF2-related tumors. EXPERIMENTAL DESIGN: A 2-stage clinical trial design was used and NF2 patients > 3 years of age with progressive NF2-related tumors including VS, meningiomas and ependymomas were eligible. Lapatinib was administered continuously for 28-day courses. MRIs of the brain and spine, including volumetric tumor analysis, as well as audiograms were performed at baseline and after every 3rd course. Primary endpoint was defined as a decrease of at least 15% in tumor volume. RESULTS: At the time of submission, enrollment on the first trial stage has been completed with 9 eligible patients. Two patients discontinued protocol therapy after 3 courses due to progression. One of 3 evaluable patients to date had a 16.6% reduction in tumor volume of his VS after 3 courses. The remaining 6 patients continue on trial. CONCLUSION: A full report of tolerance and activity will be reported on the first 9 patients, but preliminary response data suggests that lapatinib may have anti-tumor activity against VS in NF2 patients. Predefined study response criteria on stage 1 were met to allow enrollment of 8 additional patients on stage 2 of this trial
— id: 135615, year: 2010, vol: 12, page: ii43, stat: Journal Article,

INVASION IS AN IMPORTANT PROGNOSTIC FACTOR IN NEWLY DIAGNOSED HIGH-GRADE GLIOMAS
Kunnakkat, Saroj D.; Perretta, Donato; Medabalmi, Praveen; Gruber, Michael L.; Gruber, Deborah; Golfinos, John; Parker, Erik; Narayana, Ashwatha
2010 NOV ;12(2):5-5, Neuro-oncology
— id: 122728, year: 2010, vol: 12, page: 5, stat: Journal Article,

Change in Pattern of Relapse After Antiangiogenic Therapy in High-Grade Glioma
Narayana A; Kunnakkat SD; Medabalmi P; Golfinos J; Parker E; Knopp E; Zagzag D; Eagan P; Gruber D; Gruber ML
2010 Jan 1;82(1):77-82, International journal of radiation oncology biology physics
PURPOSE: Local recurrence is the dominant pattern of relapse in high-grade glioma (HGG) after conventional therapy. The recent use of antiangiogenic therapy has shown impressive radiologic and clinical responses in adult HGG. The preclinical data suggesting increased invasiveness after angiogenic blockade have necessitated a detailed analysis of the pattern of recurrence after therapy. METHODS AND MATERIALS: A total of 162 consecutive patients with HGG, either newly diagnosed (n = 58) or with recurrent disease (n = 104) underwent therapy with bevacizumab at 10 mg/kg every 2 weeks and conventional chemotherapy with or without involved field radiotherapy until disease progression. The pattern of recurrence and interval to progression were the primary aims of the present study. Diffuse invasive recurrence (DIR) was defined as the involvement of multiple lobes with or without crossing the midline. RESULTS: At a median follow-up of 7 months (range, 1-37), 105 patients had recurrence, and 79 patients ultimately developed DIR. The interval to progression was similar in the DIR and local recurrence groups (6.5 and 6.3 months, p = .296). The hazard risk of DIR increased exponentially with time and was similar in those with newly diagnosed and recurrent HGG (R(2) = 0.957). The duration of bevacizumab therapy increased the interval to recurrence (p < .0001) and improved overall survival (p < .0001). However, the pattern of relapse did not affect overall survival (p = .253). CONCLUSION: Along with an increase in median progression-free survival, bevacizumab therapy increased the risk of DIR in HGG patients. The risk of increased invasion with prolonged angiogenic blockade should be addressed in future clinical trials
— id: 138155, year: 2010, vol: 82, page: 77, stat: Journal Article,

INVASION AS A DOMINANT FEATURE OF FAILURE PATTERN IN HIGH-GRADE GLIOMAS FOLLOWING BEVACIZUMAB THERAPY
Narayana, Ashwatha; Kunnakkat, Saroj D.; Medabalmi, Praveen; Golfinos, John; Parker, Erik; Knopp, Edmond; Zagzag, David; Gruber, Deborah; Gruber, Michael L.
2010 NOV ;12(2):3-3, Neuro-oncology
— id: 122727, year: 2010, vol: 12, page: 3, stat: Journal Article,

The middle fossa approach to vestibular schwannomas: The first ten years at one institution
Coelho D.H.; Golfinos J.G.; Thomas Roland Jr. J.
2009 ;119(SUPPL .3):S281-S281, Laryngoscope
— id: 122701, year: 2009, vol: 119, page: S281, stat: Journal Article,

Consensus recommendations to accelerate clinical trials for neurofibromatosis type 2
Evans, D Gareth; Kalamarides, Michel; Hunter-Schaedle, Kim; Blakeley, Jaishri; Allen, Jeffrey; Babovic-Vuskanovic, Dusica; Belzberg, Allan; Bollag, Gideon; Chen, Ruihong; DiTomaso, Emmanuelle; Golfinos, John; Harris, Gordon; Jacob, Abraham; Kalpana, Ganjam; Karajannis, Matthias; Korf, Bruce; Kurzrock, Razelle; Law, Meng; McClatchey, Andrea; Packer, Roger; Roehm, Pamela; Rubenstein, Allan; Slattery, William 3rd; Tonsgard, James H; Welling, D Bradley; Widemann, Brigitte; Yohay, Kaleb; Giovannini, Marco
2009 Aug 15;15(16):5032-5039, Clinical cancer research
PURPOSE: Neurofibromatosis type 2 (NF2) is a rare autosomal dominant disorder associated primarily with bilateral schwannomas seen on the superior vestibular branches of the eighth cranial nerves. Significant morbidity can result from surgical treatment of these tumors. Meningiomas, ependymomas, and other benign central nervous system tumors are also common in NF2. The lack of effective treatments for NF2 marks an unmet medical need. EXPERIMENTAL DESIGN: Here, we provide recommendations from a workshop, cochaired by Drs. D. Gareth Evans and Marco Giovannini, of 36 international researchers, physicians, representatives of the biotechnology industry, and patient advocates on how to accelerate progress toward NF2 clinical trials. RESULTS: Workshop participants reached a consensus that, based on current knowledge, the time is right to plan and implement NF2 clinical trials. Obstacles impeding NF2 clinical trials and how to address them were discussed, as well as the candidate therapeutic pipeline for NF2. CONCLUSIONS: Both phase 0 and phase II NF2 trials are near-term options for NF2 clinical trials. The number of NF2 patients in the population remains limited, and successful recruitment will require ongoing collaboration efforts between NF2 clinics
— id: 104462, year: 2009, vol: 15, page: 5032, stat: Journal Article,

SWALLOWING PHYSIOLOGY AFTER SKULL BASE TUMOR RESECTION
Lazarus, C; Roland, J; Golfinos, J; DeLacure, M; Amin, M; Lalwani, A
2009 DEC ;24(4):465-465, Dysphagia
— id: 107740, year: 2009, vol: 24, page: 465, stat: Journal Article,

Antiangiogenic therapy using bevacizumab in recurrent high-grade glioma: impact on local control and patient survival
Narayana, Ashwatha; Kelly, Patrick; Golfinos, John; Parker, Erik; Johnson, Glyn; Knopp, Edmond; Zagzag, David; Fischer, Ingeborg; Raza, Shahzad; Medabalmi, Praveen; Eagan, Patricia; Gruber, Michael L
2009 Jan;110(1):173-180, Journal of neurosurgery
Object Antiangiogenic agents have recently shown impressive radiological responses in high-grade glioma. However, it is not clear if the responses are related to vascular changes or due to antitumoral effects. The authors report the mature results of a clinical study of bevacizumab-based treatment of recurrent high-grade gliomas. Methods Sixty-one patients with recurrent high-grade gliomas received treatment with bevacizumab at 10 mg/kg every 2 weeks for 4 doses in an 8-week cycle along with either irinotecan or carboplatin. The choice of concomitant chemotherapeutic agent was based on the number of recurrences and prior chemotherapy. Results At a median follow-up of 7.5 months (range 1-19 months), 50 (82%) of 61 patients relapsed and 42 patients (70%) died of the disease. The median number of administered bevacizumab cycles was 2 (range 1-7 cycles). The median progression-free survival (PFS) and overall survival (OS) were 5 (95% confidence interval [CI] 2.3-7.7) and 9 (95% CI 7.6-10.4) months, respectively, as calculated from the initiation of the bevacizumab-based therapy. Radiologically demonstrated responses following therapy were noted in 73.6% of cases. Neither the choice of chemotherapeutic agent nor the performance of a resection prior to therapy had an impact on patient survival. Although the predominant pattern of relapse was local, 15 patients (30%) had diffuse disease. Conclusions Antiangiogenic therapy using bevacizumab appears to improve survival in patients with recurrent high-grade glioma. A possible change in the invasiveness of the tumor following therapy is worrisome and must be closely monitored
— id: 90721, year: 2009, vol: 110, page: 173, stat: Journal Article,

Outcomes of Stereotactic Radiosurgery in the Management of Brain Metastasis in Patients with HER2 Positive Metastatic Breast Cancer
Raza, S; Narayana, A; Morsi, A; Parker, E; Rush, S; Golfinos, J; Novik, Y
2009 DEC 15 ;69(24):874S-874S, Cancer research
— id: 106461, year: 2009, vol: 69, page: 874S, stat: Journal Article,

Glioma vascularity correlates with reduced patient survival and increased malignancy
Russell, Stephen M; Elliott, Robert; Forshaw, David; Golfinos, John G; Nelson, Peter K; Kelly, Patrick J
2009 Sep;72(3):242-246, Surgical neurology
BACKGROUND: The objective of this study was 2-fold: (1) document the presence and degree of vascularity in gliomas of different pathologic grades and (2) determine whether the presence of abnormal vascularity, determined by catheter angiography, correlates with a shortened survival. METHODS: As part of a protocol for radiographic data acquisition that was used in a computer-assisted, stereotactic system, all patients who underwent biopsy or resection of a newly diagnosed glioma between 1994 and 2000 at our institution routinely underwent preoperative catheter angiography. The presence and degree of tumor vascularity were recorded and then correlated with survival and pathologic grade. The confounding effects of age, KPS, adjuvant treatment, and extent of resection on survival were considered. RESULTS: Two hundred thirty-one patients were included in this study. The mean follow-up of survivors was 7.8 years. Tumor vascularity correlated with a shortened survival (proportional hazards RR for survival, 0.69; 95% CI, 0.58-0.82). This correlation persisted after correction for age, KPS score, adjuvant therapy, and extent of resection (RR, 0.81; 95% CI, 0.68-0.97). Abnormal vascularity was present in 25 (30%) of 82 low-grade (WHO grade 2) gliomas. Overall, the extent of vascularity (none [120 patients, 52%], blush [63 patients, 27%], neovessels [25 patients, 11%], and arteriovenous shunting [23 patients, 10%]) correlated with worse WHO tumor grade (P < .0001). CONCLUSIONS: The presence of abnormal vascularity correlates with both a shortened survival and higher grade of malignancy. These findings underscore the importance of antiangiogenesis factor investigation and drug development for the treatment of gliomas, regardless of their pathologic grade
— id: 101316, year: 2009, vol: 72, page: 242, stat: Journal Article,

The effect of dexmedetomidine on perioperative hemodynamics in patients undergoing craniotomy
Bekker, Alex; Sturaitis, Mary; Bloom, Marc; Moric, Mario; Golfinos, John; Parker, Erik; Babu, Ramesh; Pitti, Abishabeck
2008 Oct;107(4):1340-1347, Anesthesia & analgesia
BACKGROUND: The perioperative course of patients undergoing intracranial surgery is frequently complicated by hypertensive episodes. Dexmedetomidine (DEX), an alpha-2 adrenoreceptor agonist, is gaining popularity in neuroanesthesia, because its sympatholytic and antinociceptive properties may improve hemodynamic stability at critical moments of surgery. We designed this study to assess the efficacy of DEX in controlling hypertensive responses in patients undergoing intracranial surgery. METHODS: Patients scheduled for elective craniotomy were randomly assigned to receive either sevoflurane-opioid or sevoflurane-opioid-DEX anesthesia. Bispectral index was used to maintain a similar level of hypnosis in both groups (40-50). Opioids, sevoflurane, and vasoactive medications were titrated in a routine manner, at the discretion of the blinded anesthesiologist managing the case, to maintain systolic blood pressure (SBP) targeted within 90-130 mm Hg and heart rate (HR) between 50 and 90 bpm. Hemodynamic variables were continuously recorded and stored on a computer for analysis. Efficacy of the anesthetic technique in controlling SBP or HR is inversely proportional to the area under the curve (AUC) outside the targeted range. Areas under the curves above and below targeted ranges for SBP-time (AUCsbp mm Hg*min/h) and HR-time (bpm*min/h) were compared. Coefficient of variation was used to assess hemodynamic stability. RESULTS: Seventy-two patients were recruited for the study. Computerized records of 56 patients only were analyzed because of technical problems with data collection in 14 cases. AUCsbp for above the targeted range was significantly lower for patients in the DEX group (P=0.044). The coefficient of variation for SBP or HR did not differ between groups. A significantly smaller proportion of patients in the DEX group required treatment with antihypertensive medications (12 of 28, 42% vs 24 of 28, 86%, P=0.0008). The DEX group required fewer opioids in the intraoperative period, but there were no differences in the use of sevoflurane. In the postanesthesia care unit, patients in the DEX group had fewer hypertensive episodes (1.25+/-1.55 vs 2.50+/-2.00, P=0.0114) and were discharged earlier (91+/-17 vs 130+/-27 min, P<0.0001). There were no differences in the requirement for postoperative opioids or antiemetics. CONCLUSIONS: By using indices, which assess a global hemodynamic stability of the anesthetic, we determined that intraoperative DEX infusion was effective for blunting the increases in SBP perioperatively. The use of DEX did not increase the incidence of hypotension or bradycardia, common side effects of the drug
— id: 87811, year: 2008, vol: 107, page: 1340, stat: Journal Article,

An unusual presentation and spread of an endolymphatic sac tumor
Coelho, Daniel H; Golfinos, John G; Roland, J Thomas Jr
2008 Jun;29(4):569-570, Otology & neurotology
— id: 80293, year: 2008, vol: 29, page: 569, stat: Journal Article,

Posterior fossa meningiomas presenting with Meniere's-like symptoms: case report
Coelho, Daniel H; Roland, J Thomas Jr; Golfinos, John G
2008 Nov;63(5):E1001-E1001, Neurosurgery
OBJECTIVE AND IMPORTANCE: In rare cases, posterior fossa meningiomas can involve the endolymphatic sac. Such involvement can result in endolymphatic hydrops and a constellation of symptoms suggestive of Meniere's disease. The diagnosis and management of patients with these tumors is discussed. CLINICAL PRESENTATION: Three patients, each of whom presented with symptoms consistent with Meniere's disease, were found to have posterior fossa meningiomas limited to the dura overlying the endolymphatic sac. INTERVENTION: All 3 patients were diagnosed by magnetic resonance imaging and underwent complete surgical resection. In all cases, the symptoms resolved after tumor removal. CONCLUSION: Clinicians should have a degree of suspicion of posterior fossa meningioma when patients present with symptoms suggestive of Meniere's disease. Failure to do so may result in delayed diagnosis or worse outcomes for an otherwise treatable tumor
— id: 91372, year: 2008, vol: 63, page: E1001, stat: Journal Article,

Small vestibular schwannomas with no hearing: comparison of functional outcomes in stereotactic radiosurgery and microsurgery
Coelho, Daniel H; Roland, J Thomas Jr; Rush, Stephen A; Narayana, Ashwatha; St Clair, Eric; Chung, Wayne; Golfinos, John G
2008 Nov;118(11):1909-1916, Laryngoscope
OBJECTIVES: To date, numerous studies have compared functional outcomes between stereotactic radiosurgery (SRS) and microsurgery (MS) in the treatment of vestibular schwannomas (VS). However, most of them involve tumors of difference sizes, radiation dosages, and surgical approaches. Few have systematically compared issues of dysequilibrium. By studying only patients with small tumors and no hearing, we sought to minimize confounding variables. STUDY DESIGN: A retrospective chart review and telephone questionnaire. METHODS: From 1998-2006, 31 patients with small (<1.5 cm) VS and nonserviceable hearing (American Academy of Otolaryngology-Head and Neck Surgery [AAO-HNS] Class C or D) were treated at our institution. Twenty-two were available for follow-up and telephone questionnaire, including the University of California Los Angeles Dizziness Questionnaire (UCLA-DQ). Twelve underwent SRS and 10 underwent MS. All MS patients underwent the translabyrinthine approach to their tumors. Outcomes measurements included tumor control, facial nerve function, tinnitus, trigeminal function, and imbalance. RESULTS: Patients undergoing SRS had comparable rates of tumor control, facial nerve function, tinnitus, and trigeminal function to MS patients. However, SRS did result in statistically significantly worse long-term imbalance when compared with MS patients. Detailed comparisons of the two modalities are made. CONCLUSIONS: In our study population, patients with small tumors and no serviceable hearing, these data suggest that MS results in comparable minimal morbidity with SRS, though posttreatment dysequilibrium is significantly decreased. While the authors recommend translabyrinthine resection of small VS with no hearing in patients able to tolerate surgery, the need for further prospective investigation is clear
— id: 90720, year: 2008, vol: 118, page: 1909, stat: Journal Article,

High-grade glioma before and after treatment with radiation and Avastin: initial observations
Fischer, Ingeborg; Cunliffe, Clare H; Bollo, Robert J; Raza, Shahzad; Monoky, David; Chiriboga, Luis; Parker, Erik C; Golfinos, John G; Kelly, Patrick J; Knopp, Edmond A; Gruber, Michael L; Zagzag, David; Narayana, Ashwatha
2008 Oct;10(5):700-708, Neuro-oncology
We evaluate the effects of adjuvant treatment with the angiogenesis inhibitor Avastin (bevacizumab) on pathological tissue specimens of high-grade glioma. Tissue from five patients before and after treatment with Avastin was subjected to histological evaluation and compared to four control cases of glioma before and after similar treatment protocols not including bevacizumab. Clinical and radiographic data were reviewed. Histological analysis focused on microvessel density and vascular morphology, and expression patterns of vascular endothelial growth factor-A (VEGF-A) and the hematopoietic stem cell, mesenchymal, and cell motility markers CD34, smooth muscle actin, D2-40, and fascin. All patients with a decrease in microvessel density had a radiographic response, whereas no response was seen in the patients with increased microvessel density. Vascular morphology showed apparent 'normalization' after Avastin treatment in two cases, with thin-walled and evenly distributed vessels. VEGF-A expression in tumor cells was increased in two cases and decreased in three and did not correlate with treatment response. There was a trend toward a relative increase of CD34, smooth muscle actin, D2-40, and fascin immunostaining following treatment with Avastin. Specimens from four patients with recurrent malignant gliomas before and after adjuvant treatment (not including bevacizumab) had features dissimilar from our study cases. We conclude that a change in vascular morphology can be observed following antiangiogenic treatment. There seems to be no correlation between VEGF-A expression and clinical parameters. While the phenomena we describe may not be specific to Avastin, they demonstrate the potential of tissue-based analysis for the discovery of clinically relevant treatment response biomarkers
— id: 91374, year: 2008, vol: 10, page: 700, stat: Journal Article,

Gliomas: predicting time to progression or survival with cerebral blood volume measurements at dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging
Law, Meng; Young, Robert J; Babb, James S; Peccerelli, Nicole; Chheang, Sophie; Gruber, Michael L; Miller, Douglas C; Golfinos, John G; Zagzag, David; Johnson, Glyn
2008 May;247(2):490-498, Radiology
PURPOSE: To retrospectively determine whether relative cerebral blood volume (CBV) measurements can be used to predict clinical outcome in patients with high-grade gliomas (HGGs) and low-grade gliomas (LGGs) and specifically whether patients who have gliomas with a high initial relative CBV have more rapid progression than those who have gliomas with a low relative CBV. MATERIALS AND METHODS: Approval for this retrospective HIPAA-compliant study was obtained from the Institutional Board of Research Associates, with waiver of informed consent. One hundred eighty-nine patients (122 male and 67 female patients; median age, 43 years; range, 4-80 years) were examined with dynamic susceptibility-weighted contrast material-enhanced perfusion magnetic resonance (MR) imaging and were followed up clinically with MR imaging (median follow-up, 334 days). Log-rank tests were used to evaluate the association between relative CBV and time to progression by using Kaplan-Meier curves. Binary logistic regression was used to determine whether age, sex, and relative CBV were associated with an adverse event (progressive disease or death). RESULTS: Values for the mean relative CBV for patients according to each clinical response were as follows: 1.41 +/- 0.13 (standard deviation) for complete response (n = 4), 2.36 +/- 1.78 for stable disease (n = 41), 4.84 +/- 3.32 for progressive disease (n = 130), and 3.82 +/- 1.93 for death (n = 14). Kaplan-Meier estimates of median time to progression in days indicated that patients with a relative CBV of less than 1.75 had a median time to progression of 3585 days, whereas patients with a relative CBV of more than 1.75 had a time to progression of 265 days. Age and relative CBV were also independent predictors for clinical outcome. CONCLUSION: Dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging can be used to predict median time to progression in patients with gliomas, independent of pathologic findings. Patients who have HGGs and LGGs with a high relative CBV (>1.75) have a significantly more rapid time to progression than do patients who have gliomas with a low relative CBV
— id: 91375, year: 2008, vol: 247, page: 490, stat: Journal Article,

Change in pattern of relapse following anti-angiogenic therapy in high grade glioma
Narayana, A; Golfinos, JG; Raza, S; Knopp, E; Medabalmi, P; Parker, E; Kelly, P; Zagzag, D; Gruber, M
2008 AUG ;72(1):S11-S11, International journal of radiation oncology biology physics
— id: 86794, year: 2008, vol: 72, page: S11, stat: Journal Article,

Feasibility of using bevacizumab with radiation therapy and temozolomide in newly diagnosed high-grade glioma
Narayana, Ashwatha; Golfinos, John G; Fischer, Ingeborg; Raza, Shahzad; Kelly, Patrick; Parker, Erik; Knopp, Edmond A; Medabalmi, Praveen; Zagzag, David; Eagan, Patricia; Gruber, Michael L
2008 Oct 1;72(2):383-389, International journal of radiation oncology biology physics
INTRODUCTION: Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), has shown promise in the treatment of patients with recurrent high-grade glioma. The purpose of this study is to test the feasibility of using bevacizumab with chemoradiation in the primary management of high-grade glioma. METHODS AND MATERIALS: Fifteen patients with high-grade glioma were treated with involved field radiation therapy to a dose of 59.4 Gy at 1.8 Gy/fraction with bevacizumab 10 mg/kg on Days 14 and 28 and temozolomide 75 mg/m(2). Subsequently, bevacizumab 10 mg/kg was continued every 2 weeks with temozolomide 150 mg/m(2) for 12 months. Changes in relative cerebral blood volume, perfusion-permeability index, and tumor volume measurement were measured to assess the therapeutic response. Immunohistochemistry for phosphorylated VEGF receptor 2 (pVEGFR2) was performed. RESULTS: Thirteen patients (86.6%) completed the planned bevacizumab and chemoradiation therapy. Four Grade III/IV nonhematologic toxicities were seen. Radiographic responses were noted in 13 of 14 assessable patients (92.8%). The pVEGFR2 staining was seen in 7 of 8 patients (87.5%) at the time of initial diagnosis. Six patients have experienced relapse, 3 at the primary site and 3 as diffuse disease. One patient showed loss of pVEGFR2 expression at relapse. One-year progression-free survival and overall survival rates were 59.3% and 86.7%, respectively. CONCLUSION: Use of antiangiogenic therapy with radiation and temozolomide in the primary management of high-grade glioma is feasible. Perfusion imaging with relative cerebral blood volume, perfusion-permeability index, and pVEGFR2 expression may be used as a potential predictor of therapeutic response. Toxicities and patterns of relapse need to be monitored closely
— id: 91373, year: 2008, vol: 72, page: 383, stat: Journal Article,

An Unusual Presentation and Spread of an Endolymphatic Sac Tumor
Coelho DH; Golfinos JG; Roland JT Jr
2007 Dec 28;:?-?, Otology & neurotology
— id: 91376, year: 2007, vol: , page: ?, stat: Journal Article,

Stereotactic radiosurgery for vestibular schwannomas in patients with neurofibromatosis type 2: An analysis of tumor control, complications, and hearing preservation rates - Comments
Pollock, BE; Golfinos, JG; Roland, JT; Narayana, A; Gutin, PH; Noren, G; Chen, JCT; Goodkin, R
2007 ;60(3):468-470, Neurosurgery
— id: 105550, year: 2007, vol: 60, page: 468, stat: Journal Article,

Predicting time to progression/survival in gliomas with cerebral blood volume measurements using dynamic susceptibility contrast perfusion MR imaging
Law, M; Babb, J; Peccerelli, N; Young, R; Chheang, S; Gruber, M; Golfinos, J; Miller, D; Zagzag, D; Johnson, G
2006 OCT ;8(4):494-495, Neuro-oncology
— id: 70330, year: 2006, vol: 8, page: 494, stat: Journal Article,

Perfusion magnetic resonance imaging predicts patient outcome as an adjunct to histopathology: a second reference standard in the surgical and nonsurgical treatment of low-grade gliomas
Law, Meng; Oh, Sarah; Johnson, Glyn; Babb, James S; Zagzag, David; Golfinos, John; Kelly, Patrick J
2006 Jun;58(6):1099-1107, Neurosurgery
OBJECTIVE: To determine whether relative cerebral blood volume (rCBV) can predict patient outcome, specifically tumor progression, in low-grade gliomas (LGGs) and thus provide a second reference standard in the surgical and postsurgical management of LGGs. METHODS: Thirty-five patients with histologically diagnosed LGGs (21 low-grade astrocytomas and 14 low-grade oligodendrogliomas and low-grade mixed oligoastrocytomas) were studied with dynamic susceptibility contrast-enhanced perfusion magnetic resonance imaging. Wilcoxon tests were used to compare patients in different response categories (complete response, stable, progressive, death) with respect to baseline rCBV. Log-rank tests were used to evaluate the association of rCBV with survival and time to progression. Kaplan-Meier time-to-progression curves were generated. Tumor volumes and CBV measurements were obtained at the initial examination and again at follow-up to determine the association of rCBV with tumor volume progression. RESULTS: Wilcoxon tests showed patients manifesting an adverse event (either death or progression) had significantly higher rCBV (P = 0.003) than did patients without adverse events (complete response or stable disease). Log-rank tests showed that rCBV exhibited a significant negative association with disease-free survival (P = 0.0015), such that low rCBV values were associated with longer time to progression. Kaplan-Meier curves demonstrated that lesions with rCBV less than 1.75 (n = 16) had a median time to progression of 4620 +/- 433 days, and lesions with rCBV more than 1.75 (n = 19) had a median time to progression of 245 +/- 62 days (P < 0.005). Lesions with low baseline rCBV (< 1.75) demonstrated stable tumor volumes when followed up over time, and lesions with high baseline rCBV (> 1.75) demonstrated progressively increasing tumor volumes over time. CONCLUSION: Dynamic susceptibility contrast-enhanced perfusion magnetic resonance imaging may be used to identify LGGs that are either high-grade gliomas, misdiagnosed because of sampling error at pathological examination or that have undergone angiogenesis in the progression toward malignant transformation. This suggests that rCBV measurements may be used as a second reference standard to determine the surgical management/risk-benefit equation and postsurgical adjuvant therapy for LGGs
— id: 65798, year: 2006, vol: 58, page: 1099, stat: Journal Article,

Results of surgical resection for progression of brain metastases previously treated by gamma knife radiosurgery
Truong, Minh T; St Clair, Eric G; Donahue, Bernadine R; Rush, Stephen C; Miller, Douglas C; Formenti, Silvia C; Knopp, Edmond A; Han, Kerry; Golfinos, John G
2006 Jul;59(1):86-97, Neurosurgery
OBJECTIVE: To determine treatment outcome after surgical resection for progressive brain metastases after gamma knife radiosurgery (GKR) and to explore the role of dynamic contrast agent-enhanced perfusion magnetic resonance imaging (MRI) and proton spectroscopic MRI studies (MRS/P) in predicting pathological findings. METHODS: Between 1997 and 2002, 32 patients underwent surgical resection for suspected progression of brain metastases from a cohort of 245 patients with brain metastases treated with GKR. Postradiosurgery MRI surveillance was performed at 6 and 12 weeks, and then every 12 weeks after GKR. In some cases, additional MRI scanning with spectroscopy or perfusion (MRS/P) was used to aid differentiation of radiation change from tumor progression. The decision to perform neurosurgical resection was based on MRI or clinical evidence of lesion progression among patients with a Karnofsky performance score of 60 or more and absent or stable systemic disease. RESULTS: Thirteen percent (32 out of 245) of patients and 6% (38 out of 611) of lesions required surgical resection after GKR. The median time from GKR to surgical resection was 8.6 months (range, 1.7-27.1 mo). The 6-, 12-, and 24-month actuarial survival from time of GKR was 97, 78, and 47% for the resected patients and 65, 40, and 19% for the nonresected patients (P < 0.0001). The two-year survival rate of patients requiring two resections after GKR was 100% compared with 39% for patients undergoing one resection (P = 0.02). The median survival of resected patients was 27.2 months (range, 7.0-72.5 mo) from the diagnosis of brain metastases, 19.9 months (range, 5.0-60.7 mo) from GKR, and 8.9 months (range, 0.2-53.1 mo) from surgical resection. Tumor was found in 90% of resected specimens and necrosis alone in 10%. MRS/P studies were performed in 15 resected patients. Overall, MRS/P predicted tumor in 11 lesions, confirmed pathologically in nine lesions, and necrosis alone was found in two. The MRS/P predicted necrosis alone in three, whereas pathology revealed viable tumor in two and necrosis in one lesion. CONCLUSION: Surgical intervention of progressive brain metastases after GKR in selected patients leads to a meaningful improvement in survival rates. Further studies are necessary to determine the role of MRS/P in the postradiosurgery surveillance of brain metastases
— id: 67932, year: 2006, vol: 59, page: 86, stat: Journal Article,

Resection of parietal lobe gliomas: incidence and evolution of neurological deficits in 28 consecutive patients correlated to the location and morphological characteristics of the tumor
Russell, Stephen M; Elliott, Robert; Forshaw, David; Kelly, Patrick J; Golfinos, John G
2005 Dec;103(6):1010-1017, Journal of neurosurgery
OBJECT: The goal of this study is to report the incidence and clinical evolution of neurological deficits in patients who underwent resection of gliomas confined to the parietal lobe. METHODS: Patient demographics, findings of serial neurological examinations, tumor location and neuroimaging characteristics, extent of resection, and surgical outcomes were tabulated by reviewing inpatient and office records, as well as all pre- and postoperative magnetic resonance (MR) images obtained in 28 consecutive patients who underwent resection of a glial neoplasm found on imaging studies to be confined to the parietal lobe. Neurological deficits were correlated with hemispheric dominance, location of the lesion within the superior or inferior parietal lobules, subcortical extension, and involvement of the postcentral gyrus. The tumors were located in the dominant hemisphere in 18 patients (64%); had a mean diameter of 39 mm (range 14-69 mm); were isolated to the superior parietal lobule in six patients (21%) and to the inferior parietal lobule in eight patients (29%); and involved both lobules in 14 patients (50%). Gross-total resection, documented by MR imaging, was achieved in 24 patients (86%). Postoperatively, nine patients (32%) experienced new neurological deficits, whereas seven (25%) had an improvement in their preoperative deficit. A correlation was noted between larger tumors and the presence of neurological deficits both before and after resection. Postoperatively higher-level (association) parietal deficits were noted only in patients with tumors involving both the superior and inferior parietal lobules in the dominant hemisphere. At the 3-month follow-up examination, five of nine new postoperative deficits had resolved. CONCLUSIONS: Neurological deterioration and improvement occur after resection of parietal lobe gliomas. Parietal lobe association deficits, specifically the components of Gerstmann syndrome, are mostly associated with large tumors that involve both the superior and inferior parietal lobules of the dominant hemisphere. New hemineglect or sensory extinction was not noted in any patient following resection of lesions located in the nondominant hemisphere. Nevertheless, primary parietal lobe deficits (for example, a visual field loss or cortical sensory syndrome) occurred in patients regardless of hemispheric dominance
— id: 61369, year: 2005, vol: 103, page: 1010, stat: Journal Article,

Prevention and management of cerebrospinal fluid leak following vestibular schwannoma surgery
Fishman, Andrew J; Marrinan, Michelle S; Golfinos, John G; Cohen, Noel L; Roland, J Thomas Jr
2004 Mar;114(3):501-505, Laryngoscope
OBJECTIVES/HYPOTHESIS: Postoperative cerebrospinal fluid (CSF) leak is reported in 2% to 30% of cases following vestibular schwannoma surgery. The authors' current surgical techniques for translabyrinthine, retrosigmoid transmeatal, and middle cranial fossa approaches have evolved from analysis of their prior experience in an effort to minimize their complication rate. The authors evaluated the efficacy of their current surgical technique in decreasing the postoperative CSF leak rate. STUDY DESIGN: Retrospective review. METHODS: The vestibular schwannoma database from the New York University Medical Center (New York, NY) neurotological service was reviewed. Data were extracted for type of approach, tumor size, and CSF leak rate. Liberal leak criteria were used. Surgical techniques and management of CSF leak were reviewed. RESULTS: Data from 215 patients who had surgery from 1995 to 2000 manifested a 6.6% CSF leak rate for primary surgeries. This compared favorably with the authors' 17% overall CSF leak rate in 555 total primary surgeries performed between 1979 and 1995. Translabyrinthine closure was performed with dural sutures used as a sling across the posterior fossa dura and abdominal fat placed as a series of corks through the sutures. Abdominal fat was used to obliterate the mastoid cavity in conjunction with aditus and mastoid obliteration. Attention must be paid to soft tissue obliteration of potentially open air cell tracts. Retrosigmoid transmeatal closure was performed with a soft tissue graft in the internal auditory canal drill-out held in position by a 'saloon-door' dural flap. Bone wax was used to block perimeatal cells in all cases. Watertight dural closure was achieved with a sutured temporalis fascia graft. Abdominal fat obliteration of the mastoidectomy cavity was performed with an additional firm pressure from the 'Palva' periosteal flap. Middle cranial fossa closure was performed with attention to potential air cell tracts of the internal auditory canal drill-out, as well as abdominal fat graft, tissue glue, and bone wax. Fibrin glue was used in all approaches to temporarily secure fat in situ. Management of CSF leaks starts with nonoperative measures including bed rest, oversewing of incisional wounds, and placement of a lumbar subarachnoid spinal fluid diversion drain. If these conservative measures fail, repeat exploration is necessary and is directed at identifying and corking the cell or cells (usually perimeatal or perilabyrinthine) opening directly into the posterior fossa. CONCLUSION: Evolution in surgical techniques, with particular attention to exposed air cell tracts, abdominal fat graft, and Palva periosteal flap for closure, has had a significant effect in decreasing the author's CSF leak rate after vestibular schwannoma surgery. Conservative management was successful in approximately 50% of cases. Repeat exploration, when needed, was directed at blocking the air cell tract (usually perimeatal or perilabyrinthine) responsible for the CSF leak
— id: 44805, year: 2004, vol: 114, page: 501, stat: Journal Article,

Advanced MRI for brain tumors: a neurosurgical perspective
Golfinos, John G; Tessler, Lee E; Kelly, Patrick J
2004 Oct;15(5):337-339, Topics in magnetic resonance imaging
This paper discusses the modern neurosurgeon's use of advanced magnetic resonance imaging in pre-operative and perioperative planning. The effect of advanced imaging on the risk and benefit analysis of surgery is discussed in particular
— id: 56069, year: 2004, vol: 15, page: 337, stat: Journal Article,

Cytological diagnosis of cystic brain tumors: A retrospective study of 88 cases
Hernandez, Osvaldo; Zagzag, David; Kelly, Patrick; Golfinos, John; Levine, Pascale Hummel
2004 Sep 27;31(4):221-221, Diagnostic cytopathology
The stereotaxic aspiration of cystic brain tumors is performed to provide cyst decompression and/or to facilitate surgical resection. The purpose of our study was to determine the diagnostic value of brain cyst fluid cytology, especially in clinically suspected recurrent tumors with no histological follow-up (HF), when a diagnosis is most needed. We reviewed the cytological diagnoses of 88 aspirates from 70 patients with cystic brain tumors between 1995 and 2001, of which 31 had a prior known malignancy including 18 primary brain tumors (PBTs) and 13 adenocarcinomas (ACAs). Sixty-nine of 88 aspirates were obtained intraoperatively. Nineteen of 88 aspirates were obtained from 10 patients with recurrent or persistent cystic brain tumors (8 patients with PBT and 2 patients with ACA), with available clinicoradiological correlation (magnetic resonance imaging/computed tomography [MRI/CT] scans) in 13 of them. The 88 aspirates were classified in three categories: 28 positive (32%), 15 atypical (17%), and 45 negative (51%). Eight of 28 positive cases (5 case of PBT, 2 cases of ACA, and 1 case of melanoma) were given a nonspecific diagnosis of malignant neoplasm (9% of all cases). Fifteen of 28 positive cases (6 cases of PBT, 8 cases of ACA, and 1 case of melanoma) were diagnosed correctly and confirmed by HF (17% of all cases). Four of 28 cases were ACA diagnosed solely by cytology (<4% of all cases). One neurocytoma (1/28) case was mistaken for an oligodendroglioma despite cell blocks (CBs) and immunophenotyping (IPT) (<1% of all cases). Eleven of 15 atypical cases were 8 cases of PBT, 2 cases of ACA, and 1 case of postoperative change (PC). Four of 15 atypical cases (from three patients with suspected PBT recurrence) could not be further characterized by CB/IPT and had no HF. Twenty-seven of 45 negative cases were falsely negative (23 cases of PBT, 3 cases of ACA, and 1 case of malignant neoplasm); 11/45 cases were PC, and 7/45 (from five patients with clinically suspected tumor recurrence) cases had no HF. Cytological evaluation of brain cyst fluid is not a reliable means of diagnosing cystic brain neoplasms (including recurrences) due to a high false negative rate and a low sensitivity. Most of the negative or atypical cases (68% of all cases) were recurrent PBT of glial origin that may not be prone to exfoliate. These cytological specimens consisted of lysed blood, obscuring inflammatory cells, and degenerated diagnostic cells if any, yielding inconclusive results. Diagn. Cytopathol. 2004;31:221-228.
— id: 45285, year: 2004, vol: 31, page: 221, stat: Journal Article,

Auditory brainstem implantation in patients with neurofibromatosis type 2
Kanowitz, Seth J; Shapiro, William H; Golfinos, John G; Cohen, Noel L; Roland, J Thomas Jr
2004 Dec;114(12):2135-2146, Laryngoscope
OBJECTIVES: Multichannel auditory brainstem implants (ABI) are currently indicated for patients with neurofibromatosis type II (NF2) and schwannomas involving the internal auditory canal (IAC) or cerebellopontine angle (CPA), regardless of hearing loss (HL). The implant is usually placed in the lateral recess of the fourth ventricle at the time of tumor resection to stimulate the cochlear nucleus. This study aims to review the surgical and audiologic outcomes in 18 patients implanted by our Skull Base Surgery Team from 1994 through 2003. STUDY DESIGN: A retrospective chart review of 18 patients with ABIs. METHODS: We evaluated demographic data including age at implantation, number of tumor resections before implantation, tumor size, surgical approach, and postoperative surgical complications. The ABI auditory results at 1 year were then evaluated for number of functioning electrodes and channels, hours per day of use, nonauditory side effect profile and hearing results. Audiologic data including Monosyllable, Spondee, Trochee test (MTS) Word and Stress scores, Northwestern University Children's Perception of Speech (NU-CHIPS), and auditory sensitivity are reported. RESULTS: No surgical complications caused by ABI implantation were revealed. A probe for lateral recess and cochlear nucleus localization was helpful in several patients. A range of auditory performance is reported, and two patients had no auditory perceptions. Electrode paddle migration occurred in two patients. Patient education and encouragement is very important to obtain maximum benefit. CONCLUSIONS: ABIs are safe, do not increase surgical morbidity, and allow most patients to experience improved communication as well as access to environmental sounds. Nonauditory side effects can be minimized by selecting proper stimulation patterns. The ABI continues to be an emerging field for hearing rehabilitation in patients who are deafened by NF2
— id: 47764, year: 2004, vol: 114, page: 2135, stat: Journal Article,

Differentiating surgical from non-surgical lesions using perfusion MR imaging and proton MR spectroscopic imaging
Law, Meng; Hamburger, Micole; Johnson, Glyn; Inglese, Matilde; Londono, Ana; Golfinos, John; Zagzag, David; Knopp, Edmond A
2004 Dec;3(6):557-565, Technology in Cancer Research & Treatment
Advanced MRI techniques, such as MR spectroscopy, diffusion and perfusion MR imaging can give important in vivo physiological and metabolic information, complementing morphologic findings from conventional MRI in the clinical setting. Combining perfusion MRI and MR spectroscopy can help in patients with brain masses in who the pre-operative differential diagnosis is unclear. This review demonstrates the use of dynamic, susceptibility weighted, contrast-enhanced MR imaging (DSC MRI) and magnetic resonance spectroscopic imaging (MRSI) to distinguish surgical from non-surgical lesions in the brain. There is overlap in the MRI appearance of many enhancing and ring-enhancing lesions such as gliomas, metastases, inflammatory lesions, demyelinating lesions, subacute ischemia, abscess and some AIDS related lesions. We review examples of histopathologically confirmed high-grade glioma, a middle cerebral artery territory infarct, a tumefactive demyelinating lesion and a metastasis for which conventional MR imaging (MRI) was non-specific and potentially misleading and demonstrate how DSC MRI and MRSI features were used to increase the specificity of neurodiagnosis. At several institutions, many patients routinely undergo MRI as well as MRSI and DSC MRI. Cerebral blood flow (CBF), mean transit time (MTT), and relative cerebral blood volume (rCBV) measurements are obtained from regions of maximal perfusion as determined from perfusion color overlay maps. Metabolite levels and ratios are determined for Choline (Cho), N-Acetyl Aspartate (NAA), Lactate and Lipids (LL). Metabolite levels are obtained by measuring the peak heights of each metabolite and the ratios are obtained from these measurements for Cho/Cr, Cho/NAA and NAA/Cr. Neurosurgical intervention carries substantial morbidity, mortality, financial and potential emotional cost to the patient and family. Making a pre-operative diagnosis allows the neurosurgeon to be confident in the choice of treatment plan for the patient and allays considerable patient anxiety. The utility of combining clinical findings with multi-parametric information from perfusion and spectroscopic MR imaging in differentiating surgical lesions from those which do not require surgical intervention is discussed
— id: 48876, year: 2004, vol: 3, page: 557, stat: Journal Article,

Dynamic susceptibility contrast-enhanced perfusion and conventional MR imaging findings for adult patients with cerebral primitive neuroectodermal tumors
Law, Meng; Kazmi, Khuram; Wetzel, Stephan; Wang, Edwin; Iacob, Codrin; Zagzag, David; Golfinos, John G; Johnson, Glyn
2004 Jun-Jul;25(6):997-1005, AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE: Preoperative differentiation of primitive neuroectodermal tumors (PNETs) from other tumors is important for presurgical staging, intraoperative management, and postoperative treatment. Dynamic, susceptibility-weighted, contrast-enhanced MR imaging can provide in vivo assessment of the microvasculature in intracranial mass lesions. The purpose of this study was to determine the perfusion characteristics of adult cerebral PNETs and to compare those values with low and high grade gliomas. METHODS: Conventional MR images of 12 adult patients with pathologically proved cerebral PNETs were analyzed and provided a preoperative diagnosis. Relative cerebral blood volume (rCBV) measurements and estimates of the vascular permeability transfer constant, K(trans), derived by a pharmacokinetic modeling algorithm, were also obtained. These results were compared with rCBV and K(trans) values obtained in a group of low grade gliomas (n = 30) and a group of high grade gliomas (n = 55) by using a Student t test. RESULTS: On conventional MR images, PNETs were generally well-defined contrast-enhancing masses with solid and cystic components, little or no surrounding edema, and occasional regions of susceptibility. The rCBV of cerebral PNETs was 4.76 +/- 1.99 SD, and the K(trans) was 0.0033 +/- 0.0035. A comparative group of patients with low grade gliomas (n = 30) had significantly lower rCBV (P <.0005) and lower K(trans) (P <.05). Comparison with a group of high grade gliomas showed no statistical significance in the rCBV and K(trans) (P =.53 and.19, respectively). CONCLUSION: Dynamic, susceptibility-weighted, contrast-enhanced MR imaging shows areas of increased cerebral blood volume and vascular permeability in PNETs. These results may be helpful in the diagnosis and preoperative differentiation between PNETs and other intracranial mass lesions (such as low grade gliomas), which have decreased perfusion but may sometimes have a similar conventional MR imaging appearance
— id: 43222, year: 2004, vol: 25, page: 997, stat: Journal Article,

Conventional MR imaging with simultaneous measurements of cerebral blood volume and vascular permeability in ganglioglioma
Law, Meng; Meltzer, Daniel E; Wetzel, Stephan G; Yang, Stanley; Knopp, Edmond A; Golfinos, John; Johnson, Glyn
2004 Jun;22(5):599-606, Magnetic resonance imaging
The conventional MR imaging appearance of gangliogliomas is often variable and nonspecific. Conventional MR images, relative cerebral blood volume (rCBV) and vascular permeability (K(trans)) measurements were reviewed in 20 patients with pathologically proven grade 1 and 2 gangliogliomas (n = 20) and compared to a group of grade 2 low-grade gliomas (n = 30). The conventional MRI findings demonstrated an average lesion size of 4.1 cm, contrast enhancement (n = 19), variable degree of edema, variable mass effect, necrosis/cystic areas (n = 8), well defined (n = 12), signal heterogeneity (n = 9), calcification (n = 4). The mean rCBV was 3.66 +/- 2.20 (mean +/- std) for grade 1 and 2 gangliogliomas. The mean rCBV in a comparative group of low-grade gliomas (n = 30), was 2.14 +/- 1.67. p Value < 0.05 compared with grade 1 and 2 ganglioglioma. The mean K(trans) was 0.0018 +/- 0.0035. The mean K(trans) in a comparative group of low-grade gliomas (n = 30), was 0.0005 +/- 0.001. p Value = 0.14 compared with grade 1 and 2 ganglioglioma. The rCBV measurements of grade 1 and 2 gangliogliomas are elevated compared with other low-grade gliomas. The K(trans), however, did not demonstrate a significant difference. Gangliogliomas demonstrate higher cerebral blood volume compared with other low-grade gliomas, but the degree of vascular permeability in gangliogliomas is similar to other low-grade gliomas. Higher cerebral blood volume measurements can help differentiate gangliogliomas from other low-grade gliomas
— id: 44804, year: 2004, vol: 22, page: 599, stat: Journal Article,

Comparison of cerebral blood volume and vascular permeability from dynamic susceptibility contrast-enhanced perfusion MR imaging with glioma grade
Law, Meng; Yang, Stanley; Babb, James S; Knopp, Edmond A; Golfinos, John G; Zagzag, David; Johnson, Glyn
2004 May;25(5):746-755, AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE: Relative cerebral blood volume (rCBV) and vascular permeability (K(trans)) permit in vivo assessment of glioma microvasculature. We assessed the associations between rCBV and K(trans) derived from dynamic, susceptibility-weighted, contrast-enhanced (DSC) MR imaging and tumor grade and between rCBV and K(trans). METHODS: Seventy-three patients with primary gliomas underwent conventional and DSC MR imaging. rCBVs were obtained from regions of maximal abnormality for each lesion on rCBV color maps. K(trans) was derived from a pharmacokinetic modeling algorithm. Histopathologic grade was compared with rCBV and K(trans) (Tukey honestly significant difference). Spearman and Pearson correlation factors were determined between rCBV, K(trans), and tumor grade. The diagnostic utility of rCBV and K(trans) in discriminating grade II or III tumors from grade I tumors was assessed by logistic regression. RESULTS: rCBV was significantly different for all three grades (P </=.0005). K(trans) was significantly different between grade I and grade II or III (P =.027) but not between other grades or combinations of grades. Spearman rank and Pearson correlations, respectively, were as follows: rCBV and grade, r = 0.817 and r = 0.771; K(trans) and grade, r = 0.234 and r = 0.277; and rCBV and K(trans), r = 0.266 and r = 0.163. Only rCBV was significantly predictive of high-grade gliomas (P <.0001). CONCLUSION: rCBV with strongly correlated with tumor grade; the correlation between K(trans) and tumor grade was weaker. rCBV and K(trans) were positively but weakly correlated, suggesting that these parameters demonstrate different tumor characteristics. rCBV is a more significant predictor of high-grade glioma than K(trans)
— id: 43846, year: 2004, vol: 25, page: 746, stat: Journal Article,

Cranial nerve preservation in surgery for large acoustic neuromas
Roland, J Thomas Jr; Fishman, Andrew J; Golfinos, John G; Cohen, Noel; Alexiades, George; Jackman, Alexis H
2004 May;14(2):85-90, Skull base
Facial nerve outcomes and surgical complication rates for other cranial nerves were evaluated retrospectively after the resection of large acoustic neuromas. The charts of all patients who underwent surgical removal of an acoustic neuroma between 1992 and 2001 at New York University Medical Center were reviewed. Fifty-four patients with tumors measuring 3 cm or larger were included in the study. Four patients had neurofibromatosis type 2, two of whom underwent bilateral removal of acoustic neuromas. Translabyrinthine microsurgical removal of tumor was performed in 47 of 56 cases (84%). In all cases, EMG monitoring, improved sharp microdissection, and ultrasonic aspiration were employed. Facial nerve function was assessed using the House-Brackmann facial nerve grading system immediately after surgery and at follow-up visits. A House-Brackmann grade III or better was achieved in 90% of patients, and a grade II or better was achieved in 84% of patients. Ultimate facial nerve outcome was excellent after the surgical resection of large acoustic neuromas. Preoperative cranial nerve palsies also improved after surgery. The translabyrinthine approach for tumor removal is our treatment of choice for acoustic neuromas 3 cm or larger
— id: 62125, year: 2004, vol: 14, page: 85, stat: Journal Article,

Retrolabyrinthine craniectomy: the unsung hero of skull base surgery
Russell, Stephen M; Roland, J Thomas Jr; Golfinos, John G
2004 Feb;14(1):63-71, Skull base
Despite being the foundation of, or supplement to, many skull base exposures, the retrolabyrinthine approach has not been adequately illustrated in the skull base literature. As an aid to skull base surgeons in training, this article provides a step-by-step description of the microsurgical anatomy and operative nuances of this important technique
— id: 62126, year: 2004, vol: 14, page: 63, stat: Journal Article,

A comparison of survival rates for treatment of melanoma metastatic to the brain
Stone, Anne; Cooper, Jay; Koenig, Karen L; Golfinos, John G; Oratz, Ruth
2004 ;22(4):492-497, Cancer investigation
INTRODUCTION: A retrospective review of 91 patients with brain metastases from malignant melanoma treated at New York University Medical Center between 1989-1999. Overall survival was the outcome evaluated. METHODS: Charts of 91 patients having malignant melanoma with brain metastases were reviewed. Cases were stratified according to therapy: surgical excision, surgical excision plus whole brain radiation therapy, gamma knife stereotactic radiosurgery, gamma knife stereotactic radiosurgery plus whole brain radiation therapy, and whole brain radiation therapy alone. Patients treated with gamma knife stereotactic radiosurgery plus radiation therapy were combined with patients treated with surgical excision plus radiation therapy and compared to those treated with radiation therapy alone. Prognostic characteristics of the two groups were compared and survival curves were generated using the Kaplan-Meier method. The Cox proportional hazards model was used to control for prognostic factors that differed between the groups. RESULTS: Patients treated with gamma knife stereotactic radiosurgery or surgical excision plus radiation therapy were younger, less likely to present with symptoms, and presented with fewer metastases to the brain than patients treated with radiation therapy alone. A survival benefit of 7.3 months (p = 0.05) was found to be associated with gamma knife radiosurgery or surgical excision plus radiation therapy over radiation therapy alone after controlling for differences in age, number of brain lesions, and presence of symptoms. DISCUSSION: This retrospective study of 91 patients treated for melanoma metastases to the brain attempts to examine the effectiveness of different treatments in prolonging survival. Our results suggest that surgical excision or stereotactic radiosurgery with gamma knife in addition to radiation therapy may be more effective than radiation alone at prolonging survival for patients with a limited number of brain lesions. CONCLUSION: Survival of patients with melanoma metastases to the brain may be prolonged by treatment with gamma knife stereotactic radiosurgery or surgical excision plus whole brain radiation therapy
— id: 47821, year: 2004, vol: 22, page: 492, stat: Journal Article,

Importance of MR technique for stereotactic radiosurgery
Donahue, Bernadine R; Goldberg, Judith D; Golfinos, John G; Knopp, Edmond A; Comiskey, Jessica; Rush, Stephen C; Han, Kerry; Mukhi, Vandana; Cooper, Jay S
2003 Oct;5(4):268-274, Neuro-oncology
We investigated how frequently the imaging procedure we use immediately prior to radiosurgery--triple-dose gadolinium-enhanced MR performed with the patient immobilized in a nonrelocatable head frame and 1-mm-thick MPRAGE (magnetization-prepared rapid gradient echo) images (SRS3xGado)-identifies previously unrecognized cerebral metastases in patients initially imaged by conventional MR with single-dose gadolinium (1xGado). Between July 1998 and July 2000, the diagnoses established for 47 patients who underwent radio-surgical procedures for treatment of cerebral metastases at The Gamma Knife Center of New York University were based initially on the 1xGado protocol. In July 1998, we began using SRS3xGado as our routine imaging protocol in preparation for targeting lesions for radio-surgery, using triple-dose gadolinium and acquisition of contiguous 1-mm Tl-weighted axial images. Because our SRS3xGado scans sometimes unexpectedly revealed additional metastases, we sought to learn how frequently the initial 1xGado scans would underestimate the number of metastases. We therefore reviewed the number of brain metastases identified on the SRS3xGado studies and compared the results to the number found by the 1xGado protocol, which had initially identified the brain metastases. Additional metastases, ranging from 1 to 23 lesions per patient, were identified on the SRS3xGado scan in 23 of 47 patients (49%). In 57% of the 23 patients, only one additional lesion was identified. The mean time interval between the 1xGado and the SRS3xGado scans was 20.6 days (range, 4-83 days), and the number of additional lesions detected and the time interval between two scans were negatively correlated (-0.11). The number of lesions detected on the SRS3xGado was associated only with the number of lesions on the 1xGado and not with any other patient or tumor pretreatment characteristics such as age, gender, largest tumor volume on the 1xGado, or number of days between the 1xGado and the SRS3xGado or prior surgery. The identification of additional lesions with SRS3xGado MR may have implications for patients who are treated with stereotactic radiosurgery alone (without whole-brain irradiation) with single-dose gadolinium imaging, in that unidentified lesions may go untreated. As a result of these findings we continue to use and advocate SRS3xGado scans for radiosurgery
— id: 42023, year: 2003, vol: 5, page: 268, stat: Journal Article,

Tumors of the cerebellopontine angle
Golfinos JG; Russell S; Roland JT
Textbook of neurological surgery : principles and practice Philadelphia : Lippincott, 2003,
— id: 3146, year: 2003, vol: , page: ?, stat: Chapter,

Cytologic diagnosis of cystic brain tumors: A retrospective study of 88 cases
Hernandez, O; Golfinos, J; Zagzag, D; Levine, PH
2003 ;83(Suppl 1):68A-68A, Laboratory investigation
— id: 37144, year: 2003, vol: 83, page: 68A, stat: Journal Article,

Cytologic diagnosis of cystic brain tumors: A retrospective study of 88 cases
Hernandez, O; Golfinos, J; Zagzag, D; Levine, PH
2003 ;16(Suppl 1):68A-68A, Modern pathology
— id: 38514, year: 2003, vol: 16, page: 68A, stat: Journal Article,

Pineal region lesion masquerading choroid plexus papilloma: case report
Kroppenstedt, Stefan Nikolaus; Golfinos, John; Sonntag, Volker K H; Spetzler, Robert F
2003 Feb;59(2):124-127, Surgical neurology
BACKGROUND: Choroid plexus papillomas (CPPs) are rare intracranial neoplasms, especially in the third ventricle. We report a patient with a posterior third ventricular CPP extending into the pineal that radiographically and clinically presented as a pineal region lesion. CASE DESCRIPTION: In a 51-year-old female with headache and upward gaze impairment radiological examination showed a mass in the pineal region obstructing the aqueduct of Sylvius and causing hydrocephalus. After ventriculoperitoneal shunting the tumor was approached through the infratentorial-supracerebellar approach and pathological examination revealed a typical CPP. CONCLUSIONS: This case represents an unusual presentation of an intracranial CPP. This entity should be considered an extremely rare cause of a lesion in the pineal region
— id: 42032, year: 2003, vol: 59, page: 124, stat: Journal Article,

Amusia following resection of a Heschl gyrus glioma. Case report
Russell, Stephen M; Golfinos, John G
2003 May;98(5):1109-1112, Journal of neurosurgery
The incidence and character of neurological deficits following resection of glial neoplasms localized to the Heschl gyrus are currently unknown. In this series, the authors report the clinical presentation, management, and postoperative course of three patients with right hemisphere Heschl gyrus gliomas, one of whom developed difficulty with music production and comprehension postoperatively. Resection of right hemisphere Heschl gyms gliomas can result in deficits involving music comprehension. Preliminary evidence suggests that when these deficits occur, they may be transient in nature
— id: 39228, year: 2003, vol: 98, page: 1109, stat: Journal Article,

Dynamic contrast-enhanced perfusion MR imaging measurements of endothelial permeability: differentiation between atypical and typical meningiomas
Yang, Stanley; Law, Meng; Zagzag, David; Wu, Hope H; Cha, Soonmee; Golfinos, John G; Knopp, Edmond A; Johnson, Glyn
2003 Sep;24(8):1554-1559, AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE: The measurement of relative cerebral blood volume (rCBV) and the volume transfer constant (K(trans)) by means of dynamic contrast-enhanced (DCE) perfusion MR imaging (pMRI) can be useful in characterizing brain tumors. The purpose of our study was to evaluate the utility of these measurements in differentiating typical meningiomas and atypical meningiomas. METHODS: Fifteen patients with pathologically confirmed typical meningiomas and seven with atypical meningiomas underwent conventional imaging and DCE pMRI before resection. rCBV measurements were calculated by using standard intravascular indicator dilution algorithms. K(trans) was calculated from the same DCE pMRI data by using a new pharmacokinetic modeling (PM) algorithm. Results were compared with pathologic findings. RESULTS: Mean rCBV was 8.02 +/- 4.74 in the 15 typical meningiomas and 10.50 +/- 2.1 in the seven atypical meningiomas. K(trans) was 0.0016 seconds(-1) +/- 0.0012 in the typical group and 0.0066 seconds(-1) +/- 0.0026 in the atypical group. The difference in K(trans) was statistically significant (P <.01, Student t test). Other parameters generated with the PM algorithm (plasma volume, volume of the extravascular extracellular space, and flux rate constant) were not significantly different between the two tumor types. CONCLUSION: DCE pMRI may have a role in the prospective characterization of meningiomas. Specifically, the measurement of K(trans) is of use in distinguishing atypical meningiomas from typical meningiomas
— id: 42024, year: 2003, vol: 24, page: 1554, stat: Journal Article,

Preoperative assessment of intracranial tumors with perfusion MR and a volumetric interpolated examination: a comparative study with DSA
Wetzel, Stephan G; Cha, Soonmee; Law, Meng; Johnson, Glyn; Golfinos, John; Lee, Peter; Nelson, Peter Kim
2002 Nov-Dec;23(10):1767-1774, AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE: In evaluating intracranial tumors, a safe low-cost alternative that provides information similar to that of digital subtraction angiography (DSA) may be of interest. Our purpose was to determine the utility and limitations of a combined MR protocol in assessing (neo-) vascularity in intracranial tumors and their relation to adjacent vessels and to compare the results with those of DSA. METHODS: Twenty-two consecutive patients with an intracranial tumor who underwent preoperative stereoscopic DSA were examined with contrast-enhanced dynamic T2*-weighted perfusion MR imaging followed by a T1-weighted three-dimensional (3D) MR study (volumetric interpolated brain examination [VIBE]). The maximum relative cerebral blood volume (rCBV) of the tumor was compared with tumor vascularity at DSA. Critical vessel structures were defined in each patient, and VIBE images of these structures were compared with DSA findings. For full exploitation of the 3D data sets, maximum-intensity projection algorithms reconstructed in real time with any desired volume and orientation were used. RESULTS: Tumor blush scores at DSA were significantly correlated with the rCBV measurements (r = 0.75; P <.01, Spearman rank correlation coefficient). In 17 (77%) patients, VIBE provided all relevant information about the venous system, whereas information about critical arteries were partial in 50% of the cases and not relevant in the other 50%. CONCLUSION: A fast imaging protocol consisting of perfusion MR imaging and a volumetric MR acquisition provides some of the information about tumor (neo-) vascularity and adjacent vascular anatomy that can be obtained with conventional angiography. However, the MR protocol provides insufficient visualization of distal cerebral arteries
— id: 43233, year: 2002, vol: 23, page: 1767, stat: Journal Article,

Detection of additional brain metastases with triple dose gadolinium for stereotactic radiosurgery imaging
Donahue, BR; Golfinos, JG; Rush, SC; Han, K; Holland, B; Cooper, JS
2001 Nov-Dec;7(6):31-, Cancer journal
— id: 27530, year: 2001, vol: 7, page: 31, stat: Journal Article,

Use of the LandmarX (TM) surgical navigation system in lateral skull base and temporal bone surgery - Comments for publication
Golfinos, JG; Roland, JT
2001 ;11(4):253-254, Skull base
— id: 105551, year: 2001, vol: 11, page: 253, stat: Journal Article,

A stereotactic device for experimental rat and mouse irradiation using gamma knife model B--technical note
Kamiryo T; Han K; Golfinos J; Nelson PK
2001 ;143(1):83-87, Acta neurochirurgica
BACKGROUND: For radiobiological experiments using the Gamma Knife model B, we constructed a stereotactic device to irradiate rat and mouse brains and verify the absorbed dose at the target using thermoluminescence dosimetry and a head phantom. METHODS: Our stereotactic device is primarily designed for rats using the fixation principles of a stereotactic atlas. A head-fixation adapter for a mouse was constructed to enable targeted irradiation of mouse brains. We built simple phantoms to simulate rat and mouse heads. We placed thermoluminescent dosimeters at various positions on the phantom for dose measurements. Dose planning employed the Leksell Gamma Plan version 4.11 software, assuming a spherical skull geometry for all calculations. FINDINGS: The measurements demonstrated that the actual absorbed dose agreed with our calculations within the errors of thermoluminescence dosimetry and the accuracy of our irradiation technique and dose calculations. INTERPRETATION: This device provides an accurate method for irradiating rat and mouse brains using the Gamma Knife model B
— id: 20676, year: 2001, vol: 143, page: 83, stat: Journal Article,

Head injury
Cooper, Paul R; Golfinos, John
New York : McGraw-Hill, 2000,
— id: 675, year: 2000, vol: , page: , stat: ,

Skull fracture and post-traumatic cerebrospinal fluid fistula
Golfinos JG; Cooper PR
Head injury New York : McGraw-Hill Health Professions, 2000,
— id: 3570, year: 2000, vol: , page: 155, stat: Chapter,

Nutrition in the patient with severe head injury
Mogilner A; Golfinos JG
Head injury New York : McGraw-Hill Health Professions, 2000,
— id: 3573, year: 2000, vol: , page: 517, stat: Chapter,

Glial neoplasms: dynamic contrast-enhanced T2*-weighted MR imaging
Knopp EA; Cha S; Johnson G; Mazumdar A; Golfinos JG; Zagzag D; Miller DC; Kelly PJ; Kricheff II
1999 Jun;211(3):791-798, Radiology
PURPOSE: To evaluate the role of T2*-weighted echo-planar perfusion imaging by using a first-pass gadopentetate dimeglumine technique to determine the association of magnetic resonance (MR) imaging-derived cerebral blood volume (CBV) maps with histopathologic grading of astrocytomas and to improve the accuracy of targeting of stereotactic biopsy. MATERIALS AND METHODS: MR imaging was performed in 29 patients by using a first-pass gadopentetate dimeglumine T2*-weighted echo-planar perfusion sequence followed by conventional imaging. The perfusion data were processed to obtain a color map of relative regional CBV. This information formed the basis for targeting the stereotactic biopsy. Relative CBV values were computed with a nondiffusible tracer model. The relative CBV of lesions was expressed as a percentage of the relative CBV of normal white matter. The maximum relative CBV of each lesion was correlated with the histopathologic grading of astrocytomas obtained from samples from stereotactic biopsy or volumetric resection. RESULTS: The maximum relative CBV in high-grade astrocytomas (n = 26) varied from 1.73 to 13.7, with a mean of 5.07 +/- 2.79 (+/- SD), and in the low-grade cohort (n = 3) varied from 0.92 to 2.19, with a mean of 1.44 +/- 0.68. This difference in relative CBV was statistically significant (P < .001; Student t test). CONCLUSION: Echo-planar perfusion imaging is useful in the preoperative assessment of tumor grade and in providing diagnostic information not available with conventional MR imaging. The areas of perfusion abnormality are invaluable in the precise targeting of the stereotactic biopsy
— id: 6128, year: 1999, vol: 211, page: 791, stat: Journal Article,

Use of the ISG system for 3-D craniotomy
Golfinos JG; Spetzler RF
Textbook of stereotactic and functional neurosurgery New York : McGraw-Hill, 1998,
— id: 3149, year: 1998, vol: , page: ?, stat: Chapter,

The state of the art of neuronavigation with frameless sterotaxy in intracranial neurosurgery
Lawton MT; Golfinos JG; Geldmacher TR; Spetzler RF
1998 ;1:27-38, Operative techniques in neurosurgery
— id: 42034, year: 1998, vol: 1, page: 27, stat: Journal Article,

Expression of a receptor protein tyrosine phosphatase in human glial tumors
Norman SA; Golfinos JG; Scheck AC
1998 Feb;36(3):209-217, Journal of neuro-oncology
We have analyzed expression of a receptor protein tyrosine phosphatase (RPTPzeta/beta) in tissue samples from 23 human gliomas. Using the reverse transcription-polymerase chain reaction (RT-PCR) technique, we assayed for the presence or absence of mRNA transcripts encoding the intact receptor and 2 alternatively spliced forms of RPTPzeta/beta. Transcripts encoding the intact and truncated receptors were expressed in all of the lower grade gliomas (WHO grade 1-3) analyzed, but not in 55% of the grade 4 glioblastomas multiforme (GBM). However, this subset of GBMs did express an alternatively spliced secreted form comprised of only the RPTPzeta/beta extracellular domain. Our data suggests there may be a correlation between the loss of transcripts encoding the receptor forms of RPTPzeta/beta and progression from low to high grade gliomas. This work provides additional evidence for the importance of phosphatase isoform expression in human tumors
— id: 57220, year: 1998, vol: 36, page: 209, stat: Journal Article,

Mycosis fungoides metastasizing to the brain parenchyma: case report
Zonenshayn M; Sharma S; Hymes K; Knopp EA; Golfinos JG; Zagzag D
1998 Apr;42(4):933-937, Neurosurgery
OBJECTIVE AND IMPORTANCE: Mycosis fungoides is a rare T-cell lymphoma of the skin that can, in one-half to three-quarters of patients suffering from this disease, involve the viscera in late stages of the disease. Although autopsy series performed more than 2 decades ago showed that the incidence of metastatic mycosis fungoides to the central nervous system is approximately one of seven, a total of only several dozen cases have been reported to date. As compared to meningeal involvement, intraparenchymal metastases are even rarer. We describe a biopsy-proven case of intraparenchymal central nervous system mycosis fungoides in a patient with nonprogressive skin involvement and no detectable visceral involvement, and we present a review of the relevant literature. CLINICAL PRESENTATION: A 68-year-old man, 3 years after the diagnosis of his skin disease, developed fatigue, confusion, and frontal lobe signs without the presence of cerebriform cells in the peripheral blood or any other clinical evidence of visceral involvement. Magnetic resonance imaging revealed a diffuse area of increased T2-weighted signal involving the white matter of both cerebral hemispheres as well as a focal area of T2 abnormality along the body of the corpus callosum. The radiological differential diagnosis was either leukodystrophy caused by chemotherapy, progressive multifocal leukoencephalopathy, or glioma with associated white matter changes. INTERVENTION: A stereotactic serial brain biopsy revealed diffuse perivascular infiltrates of atypical lymphocytes, as well as several large cells with cerebriform nuclei consistent with mycosis fungoides. The cells were immunoreactive for LCA, MT1, UCHL1, and CD3. CONCLUSION: We stress the importance of including mycosis fungoides as part of the differential diagnosis for a brain lesion in patients with cutaneous T-cell lymphoma, because treatments do exist, and we conclude that a serial stereotactic biopsy may be necessary to provide a definitive diagnosis
— id: 57297, year: 1998, vol: 42, page: 933, stat: Journal Article,

Expression of the genes encoding myelin basic protein and proteolipid protein in human malignant gliomas
Golfinos JG; Norman SA; Coons SW; Norman RA; Ballecer C; Scheck AC
1997 May;3(5):799-804, Clinical cancer research
Pathological differentiation of oligodendroglioma and mixed oligoastrocytoma from astrocytoma is difficult, relying on morphological characteristics due to the lack of reliable immunohistochemical stains. Oligodendrocytes, the presumed cell of origin of oligodendrogliomas, highly express the genes encoding myelin basic protein (MBP) and proteolipid protein (PLP). We analyzed the expression of these genes to determine whether they might be useful molecular markers of oligodendrocytic tumors. MBP and PLP were highly expressed in all oligodendrogliomas and minimally expressed in glioblastomas multiforme. MBP was highly expressed in mixed oligoastrocytomas, whereas PLP expression was minimal. The association between tumor classification and expression of the MBP and PLP genes was statistically significant. Expression of these genes may serve as a useful molecular marker for some subtypes of human gliomas
— id: 42025, year: 1997, vol: 3, page: 799, stat: Journal Article,

Clinical use of a frameless stereotactic arm. Results of 325 cases
Golfinos JR; Fitzpatrick BC; Smith LR; Spetzler RF
1997 ;:?-?, Year book of neurology & neurosurgery
— id: 42036, year: 1997, vol: , page: ?, stat: Journal Article,

Threaded steinmann pin fusion of the craniovertebral junction
Apostolides PJ; Dickman CA; Golfinos JG; Papadopoulos SM; Sonntag VK
1996 Jul 15;21(14):1630-1637, Spine
STUDY DESIGN: In a clinical retrospective study, the authors review long-term results of occipitocervical fusion using a wide diameter, contoured, threaded Steinmann pin. OBJECTIVES: To evaluate the clinical and radiographic results of occipitocervical fusion using this technique in a variety of abnormalities including rheumatoid arthritis. SUMMARY OF BACKGROUND DATA. The various surgical techniques and hardware developed for occipitocervical fusion have been associated with mixed results, particularly in patients with rheumatoid arthritis or basilar invagination. METHODS: Thirty-nine patients with occipitocervical instability were internally fixed with a wide diameter, contoured, threaded Steinmann pin wired to the occiput and cervical laminae or facets. Fusion was facilitated using autologous iliac crest bone graft and a cervical orthosis. Instability resulted from rheumatoid arthritis (n = 12), congenital anomalies (n = 12), trauma (n = 10), tumor (n = 4), or osteogenesis imperfecta (n = 1). Fifteen patients had radiographic evidence of basilar invagination. Long-term outcome (mean follow-up period, 38.9 months; range, 12-78 months) was based on clinical and radiographic review. RESULTS: Thirty-seven patients (97%) had a stable postoperative occipitocervical construct: there were 35 osseous unions, two fibrous unions, and one nonunion. There was on postoperative death from pulmonary complications. No patient developed evidence of new, recurrent, or progressive basilar invagination. CONCLUSION: The authors concluded that rigid segmental fixation of the craniovertebral junction using a wide diameter, contoured, threaded Steinmann pin and supplemental autograft creates excellent fusion with minimal complications. This technique is appropriate for a variety of abnormalities including rheumatoid arthritis
— id: 42027, year: 1996, vol: 21, page: 1630, stat: Journal Article,

Penetrating spine cord injury
Dickman CA; Golfinos JG
The practice of neurosurgery Baltimore : Williams & Wilkins, 1996,
— id: 3147, year: 1996, vol: , page: ?, stat: Chapter,

Stereotactic volumetric resection of low-grade gliomas
Golfinos JG; Kelly PJ
1996 ;2(3):165-173, Techniques in neurosurgery
— id: 33814, year: 1996, vol: 2, page: 165, stat: Journal Article,

The genetics of intracranial vascular malformations
Golfinos JG; Zabramski JM
1996 ;8:?-?, Concepts in neurosurgery
— id: 42037, year: 1996, vol: 8, page: ?, stat: Journal Article,

Clinical use of a frameless stereotactic arm. Results of 325 cases
Golfinos JR; Fitzpatrick BC; Smith LR; Spetzler RF
1996 March;:?-?, Key neurology & neurosurgery
— id: 42035, year: 1996, vol: , page: ?, stat: Journal Article,

Balloon angioplasty for symptomatic vasospasm
Khayata MH; Golfinos JG; Wakhloo AK; Gobin YP; Spetzler RF
Controversies in neurosurgery New York : Thieme, 1996,
— id: 3150, year: 1996, vol: , page: ?, stat: Chapter,

The contralateral transcallosal approach: experience with 32 patients
Lawton MT; Golfinos JG; Spetzler RF
1996 Oct;39(4):729-734, Neurosurgery
OBJECTIVE: To demonstrate the usefulness of the contralateral transcallosal approach for resecting lesions located laterally in or adjacent to the lateral ventricle. METHODS: Modifications to the standard ipsilateral transcallosal technique include positioning the head with the midline oriented horizontally, placing the side with the lesion up, and performing the craniotomy and interhemispheric dissection on the contralateral side. This approach avoids a transcortical incision, allows gravity to hold open the interhemispheric fissure, and increases the lateral exposure of the lesion. This approach was used in 32 patients with a variety of lesions, including 6 cavernous malformations, 7 arteriovenous malformations, and 19 tumors of various types. All but three lesions were located on the left side. RESULTS: All six cavernous malformations, all four benign tumors, and four of the seven arteriovenous malformations were resected completely. Malignant tumors were resected subtotally, and three arteriovenous malformations required stereotactic radiosurgery to treat residual deep nidus. There was no surgical mortality. Two patients experienced neurological deterioration. CONCLUSION: The contralateral transcallosal approach can be used to treat a variety of lesions safely and successfully
— id: 42026, year: 1996, vol: 39, page: 729, stat: Journal Article,

Skull base tumors. A critical appraisal and clinical series employing image guidance
Robinson JR Jr; Golfinos JG; Spetzler RF
1996 Apr;7(2):297-311, Neurosurgery clinics of North America
Two of the most significant developments in neurosurgery over the past ten years have been the application of intraoperative navigational units and the widespread use of 'skull base' surgical techniques. These developments have independently revolutionized the way in which neurosurgeons approach intracranial pathology. The combination of these two developments has had a profound effect in our clinical practice to improve outcome and extend our capabilities. This ability to see around the corner, 'x-ray' vision as some have called it, provides an added measure of safety for the patient while allowing the surgeon to treat the lesion in a more aggressive fashion
— id: 42028, year: 1996, vol: 7, page: 297, stat: Journal Article,

Clinical use of a frameless stereotactic arm: results of 325 cases
Golfinos JG; Fitzpatrick BC; Smith LR; Spetzler RF
1995 Aug;83(2):197-205, Journal of neurosurgery
The viewing wand is a frameless stereotactic arm that can be used in conjunction with computerized tomography (CT) or magnetic resonance (MR) imaging to provide image-based intraoperative navigation. The authors report a series of 325 cases in which the viewing wand was used and evaluated for its utility, ease of integration into the standard surgical setup, reliability, and real-world accuracy. The use of the system was associated with minimal additional effort or time spent in setting up the procedure as long as a trained technician performed the data transfer and reconstruction. The viewing wand was used in 165 cases in conjunction with CT and 145 cases with MR imaging. The system was reliable, achieving a useful registration in 310 of 325 cases (95.4%). Fiducial-based registration was more accurate than an anatomical landmark-surface fit algorithm method of registration (mean 2.8 vs. 5.6 mm error, respectively, for CT; and mean 3.0 vs. 6.2 mm for MR imaging). The actual error of the system in estimating the position of the probe tip just after registration was judged by the operating surgeon to be less than 2 mm in 92% of MR imaging cases and in 82% of CT cases, between 2 and 5 mm in 7% of MR imaging and 17% of CT cases, and greater than 5 mm in less than 1% of MR imaging and 1.2% of CT cases. The accuracy of the system degraded during the operation, so that by the third evaluation the error was estimated to be less than 2 mm in 77% of MR imaging and 62% of CT cases. Overall, the viewing wand was found to be reliable and accurate. This real-world accuracy was sufficient for a broad range of applications including glioma resection, cerebrospinal fluid shunting procedures, resection of small subcortical masses, and temporal lobe resection. The system is a useful navigational aid that allows a direct approach to intracranial pathology without the drawbacks of application and the limitations of a stereotactic frame
— id: 42029, year: 1995, vol: 83, page: 197, stat: Journal Article,

Repair of vertebral artery injury during anterior cervical decompression
Golfinos JG; Dickman CA; Zabramski JM; Sonntag VK; Spetzler RF
1994 Nov 15;19(22):2552-2556, Spine
METHODS. Vertebral artery injury is a rarely described complication of anterior cervical decompression. The authors performed a retrospective review of their operative database for the purposes of defining the optimal management of this complication and its avoidance. RESULTS. Four of 1,215 (0.3%) patients undergoing anterior cervical operation sustained arterial injuries. In three cases, primary repair of the artery was successful; in one case, the artery was exposed and ligated. There were no postoperative ischemic complications. Artery laceration occurred during decompression (n = 2), screw tapping (n = 1), and during soft tissue retraction (n = 1). CONCLUSIONS. Injury to the vertebral artery during anterior approaches can be avoided by preoperative identification of anomalous arteries and by intraoperative attention to the midline. When the artery is injured, primary repair may be the optimal management strategy
— id: 42030, year: 1994, vol: 19, page: 2552, stat: Journal Article,

Are the calcium antagonists really useful in cerebral aneurysmal surgery? A retrospective study
Golfinos JG; Thompson BG; Zabramski JM; Spetzler RF
1994 Sep;35(3):541-542, Neurosurgery
— id: 42031, year: 1994, vol: 35, page: 541, stat: Journal Article,

Cerebral protection
Golfinos JG; Zabramski JM
Neurovascular surgery New York : McGraw Hill, 1994,
— id: 3148, year: 1994, vol: , page: 175, stat: Chapter,

The natural history of familial cavernous malformations: results of an ongoing study
Zabramski JM; Wascher TM; Spetzler RF; Johnson B; Golfinos J; Drayer BP; Brown B; Rigamonti D; Brown G
1994 Mar;80(3):422-432, Journal of neurosurgery
Cavernous malformations are congenital abnormalities of the cerebral vessels that affect 0.5% to 0.7% of the population. They occur in two forms: a sporadic form characterized by isolated lesions, and a familial form characterized by multiple lesions with an autosomal dominant mode of inheritance. The management of patients with cavernous malformations, particularly those with the familial form of the disease, remains a challenge because little is known regarding the natural history. The authors report the results of an ongoing study in which six families afflicted by familial cavernous malformations have been prospectively followed with serial interviews, physical examinations, and magnetic resonance (MR) imaging at 6- to 12-month intervals. A total of 59 members of these six families were screened for protocol enrollment; 31 (53%) had MR evidence of familial cavernous malformations. Nineteen (61%) of these 31 patients were symptomatic, with seizures in 12 (39%), recurrent headaches in 16 (52%), focal sensory/motor deficits in three (10%), and visual field deficits in two (6%). Twenty-one of these 31 patients underwent at least two serial clinical and MR imaging examinations. A total of 128 individual cavernous malformations (mean 6.5 +/- 3.8 lesions/patient) were identified and followed radiographically. During a mean follow-up period of 2.2 years (range 1 to 5.5 years), serial MR images demonstrated 17 new lesions in six (29%) of the 21 patients; 13 lesions (10%) showed changes in signal characteristics, and five lesions (3.9%) changed significantly in size. The incidence of symptomatic hemorrhage was 1.1% per lesion per year. The results of this study demonstrate that the familial form of cavernous malformations is a dynamic disease; serial MR images revealed changes in the number, size, and imaging characteristics of lesions consistent with acute or resolving hemorrhage. It is believed that the de novo development of new lesions in this disease has not been previously reported. These findings suggest that patients with familial cavernous malformations require careful follow-up monitoring, and that significant changes in neurological symptoms warrant repeat MR imaging. Surgery should be considered only for lesions that produce repetitive or progressive symptoms. Prophylactic resection of asymptomatic lesions does not appear to be indicated
— id: 42033, year: 1994, vol: 80, page: 422, stat: Journal Article,

Definitions and pathologic features
Johnson PJ; Wascher TM; Golfinos JG; et al
Cavernous malformations Park Ridge IL: American Association of Neurological Surgeons, 1993,
— id: 3151, year: 1993, vol: , page: ?, stat: Chapter,

The management of unruptured intracranial vascular malformations
Golfinos JG; Wascher TM; Aabramski JM; et al
1992 ;8:2-11, BNI quarterly
— id: 42038, year: 1992, vol: 8, page: 2, stat: Journal Article,

Pallidotomy in the levodopa era
Greene KA; Marciano FF; Golfinos JG; et al
1992 ;2:257-281, Advances in clinical neurosciences
— id: 42040, year: 1992, vol: 2, page: 257, stat: Journal Article,

Management of unruptured intracranial aneurysms
Wascher TM; Golfinos JG; Zabramski JM; et al
1992 ;8:2-7, BNI quarterly
— id: 42039, year: 1992, vol: 8, page: 2, stat: Journal Article,