Network


Latest external collaboration on country level. Dive into details by clicking on the dots.

Hotspot


Dive into the research topics where John Y. K. Lee is active.

Publication


Featured researches published by John Y. K. Lee.


Nature Genetics | 2014

Exome sequencing identifies BRAF mutations in papillary craniopharyngiomas

Priscilla K. Brastianos; Amaro Taylor-Weiner; Peter Manley; Robert T. Jones; Dora Dias-Santagata; Aaron R. Thorner; Michael S. Lawrence; Fausto J. Rodriguez; Lindsay A. Bernardo; Laura Schubert; Ashwini Sunkavalli; Nick Shillingford; Monica L. Calicchio; Hart G.W. Lidov; Hala Taha; Maria Martinez-Lage; Mariarita Santi; Phillip B. Storm; John Y. K. Lee; James N. Palmer; Nithin D. Adappa; R. Michael Scott; Ian F. Dunn; Edward R. Laws; Chip Stewart; Keith L. Ligon; Mai P. Hoang; Paul Van Hummelen; William C. Hahn; David N. Louis

Craniopharyngiomas are epithelial tumors that typically arise in the suprasellar region of the brain. Patients experience substantial clinical sequelae from both extension of the tumors and therapeutic interventions that damage the optic chiasm, the pituitary stalk and the hypothalamic area. Using whole-exome sequencing, we identified mutations in CTNNB1 (β-catenin) in nearly all adamantinomatous craniopharyngiomas examined (11/12, 92%) and recurrent mutations in BRAF (resulting in p.Val600Glu) in all papillary craniopharyngiomas (3/3, 100%). Targeted genotyping revealed BRAF p.Val600Glu in 95% of papillary craniopharyngiomas (36 of 39 tumors) and mutation of CTNNB1 in 96% of adamantinomatous craniopharyngiomas (51 of 53 tumors). The CTNNB1 and BRAF mutations were clonal in each tumor subtype, and we detected no other recurrent mutations or genomic aberrations in either subtype. Adamantinomatous and papillary craniopharyngiomas harbor mutations that are mutually exclusive and clonal. These findings have important implications for the diagnosis and treatment of these neoplasms.


Neurosurgery | 2002

Long-term results after stereotactic radiosurgery for patients with cavernous malformations.

Toshinori Hasegawa; James McInerney; Douglas Kondziolka; John Y. K. Lee; John C. Flickinger; L. Dade Lunsford

OBJECTIVE Stereotactic radiosurgery has been used for patients with high-risk cavernous malformations of the brain. We performed radiosurgery for patients with symptomatic, imaging-confirmed hemorrhages for which resection was believed to be associated with high risk. This study examines the long-term hemorrhage rate after radiosurgery. METHODS We reviewed data obtained before and after gamma knife radiosurgery on 82 patients treated between 1987 and 2000. Most patients had multiple hemorrhages from brainstem or diencephalic cavernous malformations. Follow-up data were examined to identify hemorrhages, and an overall hemorrhage rate was calculated. RESULTS Observation before treatment averaged 4.33 years (range, 0.17–18 yr) for a total of 354 patient-years. During this period, 202 hemorrhages were observed, for an annual hemorrhage rate of 33.9%, excluding the first hemorrhage. Temporal clustering of hemorrhages was not significant. After radiosurgery, patient follow-up averaged 5 years (range, 0.42–12.08 yr), for a total of 401 patient-years. During this period, 19 hemorrhages were identified, 17 in the first 2 years posttreatment and 2 after 2 years. The annual hemorrhage rate was 12.3% per year for the first 2 years after radiosurgery, followed by 0.76% per year from Years 2 to 12. Eleven patients had new neurological symptoms without hemorrhage after radiosurgery (13.4%). The symptoms were minor in six of these patients and temporary in five. CONCLUSION Radiosurgery confers a reduction in the risk of hemorrhage for high-risk cavernous malformations. Risk reduction, although in evidence during initial follow-up, is most pronounced after 2 years. Given the difficulty of identifying high-risk patients, treatment after one major hemorrhage should be considered in selected younger patients. Such a strategy warrants further investigation.


Surgical Neurology | 2003

The effect of radiosurgeryduring management of aggressive meningiomas

Anthony E. Harris; John Y. K. Lee; Bennett Omalu; John C. Flickinger; Douglas Kondziolka; L. Dade Lunsford

BACKGROUND Aggressive (atypical or malignant) meningiomas are difficult tumors to manage. We review the local control and survival rates of patients with aggressive meningiomas after multi-modality therapy that included stereotactic radiosurgery (SRS). METHODS Thirty patients had SRS for treatment of malignant (n = 12) or atypical (n = 18) meningiomas. There were 17 (57%) males and 13 (43%) females with an average age of 58 years. The mean number of prior surgical resections was two. The median imaging follow-up was 2.3 (0.1-11.4) years; median clinical follow-up was 3.8 (0.25-11.5) years. RESULTS After SRS, the overall median time until progression of neurologic signs was 48.0 (+/-6.51) months. Median time to neurologic progression was significantly worse for patients treated late after recurrence versus early after craniotomy. Atypical meningiomas had 5- and 10-year overall actuarial survival rates of 59% (+/-13), while malignant meningiomas had 5- and 10-year overall actuarial survival rates of 59% (+/-16) and 0%. These curves were not significantly different from one another. Atypical meningiomas had a 5-year progression-free survival (PFS) of 83% (+/-7%), while malignant meningiomas had a 5-year PFS of 72% (+/-10) (p = 0.018). On multivariate analysis, early SRS and smaller tumor volumes were associated with better PFS, while younger age was associated with better survival. One patient had an adverse radiation effect after SRS. CONCLUSIONS Stereotactic radiosurgery is an important adjuvant management strategy for residual tumors identified early after craniotomy and partial resection. Aggressive use of early boost radiosurgery following craniotomy and radiation therapy is recommended for patients with malignant meningiomas.


Journal of Neurosurgery | 2008

Gamma Knife thalamotomy for essential tremor

Douglas Kondziolka; Joseph Ong; John Y. K. Lee; Robert Y. Moore; John C. Flickinger; L. Dade Lunsford

OBJECTIVES The purpose of this study was to evaluate the results following Gamma Knife thalamotomy (GKT) for medically refractory essential tremor in a series of patients in whom open surgical techniques were not desirable. METHODS Thirty-one patients underwent GKT for disabling essential tremor after medical therapy had failed. Their mean age was 77 years. Most patients were elderly or had concomitant medical illnesses. A single 4-mm isocenter was used to target a maximum dose of 130 or 140 Gy to the nucleus ventralis intermedius. Items from the Fahn-Tolosa-Marin clinical tremor rating scale were used to grade tremor and handwriting before and after radiosurgery. RESULTS The median follow-up was 36 months. In the group of 26 evaluable patients, the mean tremor score (+/- standard deviation) was 3.7 +/- 0.1 preoperatively and 1.7 +/- 0.3 after radiosurgery (p < 0.000015). The mean handwriting score was 2.8 +/- 0.2 before GKT and 1.7 +/- 0.2 afterward (p < 0.0002). After radiosurgery, 18 patients (69%) showed improvement in both action tremor and writing scores, 6 (23%) only in action tremor scores, and 3 (12%) in neither tremor nor writing. Permanent mild right hemiparesis and speech impairment developed in 1 patient 6 months after radiosurgery. Another patient had transient mild right hemiparesis and dysphagia. CONCLUSIONS Gamma Knife thalamotomy is a safe and effective therapy for medically refractory essential tremor. Its use is especially valuable for patients ineligible for radiofrequency thalamotomy or deep brain stimulation. Patients must be counseled on potential complications, including the low probability of a delayed neurological deficit.


Journal of Neurosurgery | 2013

Gamma Knife radiosurgery for the management of nonfunctioning pituitary adenomas: A multicenter study

Jason P. Sheehan; Robert M. Starke; David Mathieu; Byron Young; Penny K. Sneed; Veronica L. Chiang; John Y. K. Lee; Hideyuki Kano; Kyung Jae Park; Ajay Niranjan; Douglas Kondziolka; Gene H. Barnett; Stephen Rush; John G. Golfinos; L. Dade Lunsford

OBJECT Pituitary adenomas are fairly common intracranial neoplasms, and nonfunctioning ones constitute a large subgroup of these adenomas. Complete resection is often difficult and may pose undue risk to neurological and endocrine function. Stereotactic radiosurgery has come to play an important role in the management of patients with nonfunctioning pituitary adenomas. This study examines the outcomes after radiosurgery in a large, multicenter patient population. METHODS Under the auspices of the North American Gamma Knife Consortium, 9 Gamma Knife surgery (GKS) centers retrospectively combined their outcome data obtained in 512 patients with nonfunctional pituitary adenomas. Prior resection was performed in 479 patients (93.6%) and prior fractionated external-beam radiotherapy was performed in 34 patients (6.6%). The median age at the time of radiosurgery was 53 years. Fifty-eight percent of patients had some degree of hypopituitarism prior to radiosurgery. Patients received a median dose of 16 Gy to the tumor margin. The median follow-up was 36 months (range 1-223 months). RESULTS Overall tumor control was achieved in 93.4% of patients at last follow-up; actuarial tumor control was 98%, 95%, 91%, and 85% at 3, 5, 8, and 10 years postradiosurgery, respectively. Smaller adenoma volume (OR 1.08 [95% CI 1.02-1.13], p = 0.006) and absence of suprasellar extension (OR 2.10 [95% CI 0.96-4.61], p = 0.064) were associated with progression-free tumor survival. New or worsened hypopituitarism after radiosurgery was noted in 21% of patients, with thyroid and cortisol deficiencies reported as the most common postradiosurgery endocrinopathies. History of prior radiation therapy and greater tumor margin doses were predictive of new or worsening endocrinopathy after GKS. New or progressive cranial nerve deficits were noted in 9% of patients; 6.6% had worsening or new onset optic nerve dysfunction. In multivariate analysis, decreasing age, increasing volume, history of prior radiation therapy, and history of prior pituitary axis deficiency were predictive of new or worsening cranial nerve dysfunction. No patient died as a result of tumor progression. Favorable outcomes of tumor control and neurological preservation were reflected in a 4-point radiosurgical pituitary score. CONCLUSIONS Gamma Knife surgery is an effective and well-tolerated management strategy for the vast majority of patients with recurrent or residual nonfunctional pituitary adenomas. Delayed hypopituitarism is the most common complication after radiosurgery. Neurological and cranial nerve function were preserved in more than 90% of patients after radiosurgery. The radiosurgical pituitary score may predict outcomes for future patients who undergo GKS for a nonfunctioning adenoma.


Journal of Neurosurgery | 2017

Stereotactic radiosurgery for cerebral arteriovenous malformations: evaluation of long-term outcomes in a multicenter cohort.

Robert M. Starke; Hideyuki Kano; Dale Ding; John Y. K. Lee; David Mathieu; Jamie Whitesell; John T. Pierce; Paul P. Huang; Douglas Kondziolka; Chun Po Yen; Caleb Feliciano; Rafael Rodgriguez-Mercado; Luis Almodovar; Daniel R. Pieper; I.S. Grills; Danilo Silva; Mahmoud Abbassy; Symeon Missios; Gene H. Barnett; L. Dade Lunsford; Jason P. Sheehan

OBJECTIVE In this multicenter study, the authors reviewed the results following Gamma Knife radiosurgery (GKRS) of cerebral arteriovenous malformations (AVMs), determined predictors of outcome, and assessed predictive value of commonly used grading scales based upon this large cohort with long-term follow-up. METHODS Data from a cohort of 2236 patients undergoing GKRS for cerebral AVMs were compiled from the International Gamma Knife Research Foundation. Favorable outcome was defined as AVM obliteration and no posttreatment hemorrhage or permanent symptomatic radiation-induced complications. Patient and AVM characteristics were assessed to determine predictors of outcome, and commonly used grading scales were assessed. RESULTS The mean maximum AVM diameter was 2.3 cm, with a mean volume of 4.3 cm3. A mean margin dose of 20.5 Gy was delivered. Mean follow-up was 7 years (range 1-20 years). Overall obliteration was 64.7%. Post-GRKS hemorrhage occurred in 165 patients (annual risk 1.1%). Radiation-induced imaging changes occurred in 29.2%; 9.7% were symptomatic, and 2.7% had permanent deficits. Favorable outcome was achieved in 60.3% of patients. Patients with prior nidal embolization (OR 2.1, p < 0.001), prior AVM hemorrhage (OR 1.3, p = 0.007), eloquent location (OR 1.3, p = 0.029), higher volume (OR 1.01, p < 0.001), lower margin dose (OR 0.9, p < 0.001), and more isocenters (OR 1.1, p = 0.011) were more likely to have unfavorable outcomes in multivariate analysis. The Spetzler-Martin grade and radiosurgery-based AVM score predicted outcome, but the Virginia Radiosurgery AVM Scale provided the best assessment. CONCLUSIONS GKRS for cerebral AVMs achieves obliteration and avoids permanent complications in the majority of patients. Patient, AVM, and treatment parameters can be used to predict long-term outcomes following radiosurgery.


Operations Research Letters | 2010

Da Vinci Robot-assisted transoral odontoidectomy for basilar invagination.

John Y. K. Lee; Bradley Lega; Deb A. Bhowmick; Jason G. Newman; Bert W. O'Malley; Greg Weinstein; M. Sean Grady; William C. Welch

The transoral approach is an effective way to decompress the craniocervical junction due to basilar invagination. This approach has been described and refined, but significant limitations and technical challenges remain. Specifically, should the transoral route be used for intradural pathology, such as a meningioma, or should an inadvertent durotomy occur during extradural dissection, achieving a watertight closure of the dura in such a deep and narrow working channel is limited with the current microscopic and endoscopic techniques. Even closure of the posterior pharyngeal mucosa can be challenging, and problems with wound dehiscence encountered in some case series may be attributable to this difficulty. These problems, and the corollary aversion to the procedure felt by many neurosurgeons, led our group to investigate an alternative approach.


Neurosurgery | 2004

Loss of heterozygosity analysis of benign, atypical, and anaplastic meningiomas.

John Y. K. Lee; Sydney D. Finkelstein; Ronald L. Hamilton; Rapaka Rekha; Joseph T. King; Bennett Omalu

OBJECTIVE: Up to 70% of typical meningiomas demonstrate allelic loss at chromosome 22q. Allelic loss at additional chromosomal loci is associated with atypia and anaplasia in meningiomas. The pattern of allelic loss or loss of heterozygosity (LOH) follows a nonrandom, multistep pattern. METHODS: All surgical meningioma samples obtained from 1991 to 1992 at the University of Pittsburgh Medical Center were analyzed according to current World Health Organization criteria. Samples without constitutional deoxyribonucleic acid (DNA) were excluded from this analysis. Individual hematoxylin and eosin slides from 43 patients were microdissected, and the DNA was harvested and amplified in the presence of 24 pairs of polymerase chain reaction primers, representing 24 microsatellite loci. The polymerase chain reaction products were subjected to capillary gel electrophoresis and a fluorescence-based DNA analysis system. LOH was defined as ratios of allelic peak heights falling within a conservative threshold of less than 0.5 or more than 2.0. Fisher’s exact test and receiver operator characteristic curves were used to test the relationship between benign versus atypical and malignant pathological features and LOH at specific loci or combinations of loci. RESULTS: On review by two independent pathologists, 34 benign meningiomas, 6 atypical meningiomas, and 3 anaplastic meningiomas were identified. The mean number of alleles with LOH was 1.5 ± 1.2 for benign meningiomas, 6.7 ± 2.7 for atypical meningiomas, and 8.3 ± 2.3 for anaplastic meningiomas (P < 0.001). The most important individual loci to predict malignancy were D1S407 (P = 0.006), L-myc (P < 0.001), D10S520 (P = 0.003), D10S1173 (P = 0.042), D11S1920 (P < 0.001), D14S555 (P = 0.041), D17S1289 (P < 0.001), D22S417 (P = 0.001), D22S431 (P = 0.019), and D22S532 (P = 0.028). Combining the LOH data across loci, the area under the receiver operator characteristic curve was 0.993, corresponding to virtually perfect prediction of pathological characteristics. CONCLUSION: Microsatellite marker analysis of allelic loss is a useful method of predicting atypia and anaplasia in meningiomas. More regions of allelic loss are seen in anaplastic and atypical meningiomas as compared with benign meningiomas. This study confirms previously reported chromosomal regions of allelic loss in atypical and anaplastic meningiomas and suggests additional chromosomal regions that may represent heretofore uncharacterized deletions within meningiomas. This type of genetic fingerprint ultimately may serve both a diagnostic and therapeutic role.


Journal of Neurosurgery | 2010

Development of and psychometric testing for the Brief Pain Inventory-Facial in patients with facial pain syndromes

John Y. K. Lee; H. Isaac Chen; Christopher Urban; Anahita Hojat; Ephraim Church; Sharon X. Xie; John T. Farrar

OBJECT Outcomes in clinical trials on trigeminal pain therapies require instruments with demonstrated reliability and validity. The authors evaluated the Brief Pain Inventory (BPI) in its existing form plus an additional 7 facial-specific items in patients referred to a single neurosurgeon for a diagnosis of facial pain. The complete 18-item instrument is referred to as the BPI-Facial. METHODS This study was a cross-sectional analysis of patients who completed the BPI-Facial. The diagnosis of classic versus atypical trigeminal neuralgia (TN) was made before analyzing the questionnaire results. A hypothesis-driven factor analysis was used to determine the principal components of the questionnaire. Item reliability and questionnaire validity were tested for these specific constructs. RESULTS Data from 156 patients were analyzed, including 114 patients (73%) with classic and 42 (27%) with atypical TN. Using orthomax rotation factor analysis, 3 factors with an eigenvalue > 1.0 were identified-pain intensity, interference with general activities, and facial-specific pain interference-accounting for 97.6% of the observed item variance. Retention of the 3 factors was confirmed via a Cattell scree plot. Internal reliability was demonstrated by calculating Cronbachs alpha: 0.86 for pain intensity, 0.89 for interference with general activities, 0.95 for facial-specific pain interference, and 0.94 for the entire instrument. Initial validity of the BPI-Facial instrument was supported by the detection of statistically significant differences between patients with classic versus atypical pain. Patients with atypical TN rated their facial pain as more intense (atypical 6.24 vs classic 5.03, p = 0.013) and as having greater interference in general activities (atypical 6.94 vs classic 5.43, p = 0.0033). Both groups expressed high levels of facial-specific pain interference (atypical 6.34 vs classic 5.95, p = 0.527). CONCLUSIONS The BPI-Facial is a rigorous measure of facial pain in patients with TN and appears to have sound psychometric properties and is responsive to differences between classic and atypical TN. Future studies must assess the instruments test-retest reliability, validity in additional populations, and responsiveness with respect to changes in patient outcomes following neurosurgical interventions and medical therapies.


World Neurosurgery | 2014

Skull Base Chordoma and Chondrosarcoma: Influence of Clinical and Demographic Factors on Prognosis: A SEER Analysis

Leif-Erik Bohman; Matthew J. Koch; Robert L. Bailey; Michelle Alonso-Basanta; John Y. K. Lee

OBJECTIVE Chordomas and chondrosarcomas are rare skull base tumors, with similar radiographic and clinical presentations. We investigated factors influencing long-term survival in these 2 tumors using the Surveillance Epidemiology and End Results (SEER) database. METHODS Patients with chordoma (n = 416) and chondrosarcoma (n = 269) within the skull base from 1983 to 2009 were identified within the SEER database. Kaplan-Meier curves and Cox proportional hazards models were used to test associations with survival. t tests and χ(2) tests were used to compare groups. RESULTS Chordoma and chondrosarcoma patients were similar demographically. Survival at 5 years was 65% for chordomas and 81.8% (P < 0.0001) for chondrosarcomas and at 10 years was 32.3% and 49.5% (P = 0.004). Multivariate analysis demonstrated chordomas had a worse prognosis even when we controlled for age and tumor size (hazard ratio 3.0, 95% confidence interval 1.9-4.7, P < 0.0001). For chordomas, multivariate analysis demonstrated increasing age and tumor size were significantly associated with reduced survival. For chondrosarcomas, multivariate analysis demonstrated older age, earlier decade of diagnosis, and mesenchymal subtype were significantly associated with reduced survival. Postoperative radiation was given to 42% and 41% of patients with chordomas and chondrosarcomas, respectively. The addition of radiation did not improve survival. CONCLUSION Consistent with previous case series, skull base chordomas have significantly worse prognosis than chondrosarcomas. Patients in the SEER database had worse survival overall compared with existing case series for both chordomas and chondrosarcomas, suggesting selection bias in the existing literature.

Collaboration


Dive into the John Y. K. Lee's collaboration.

Top Co-Authors

Avatar

James N. Palmer

University of Pennsylvania

View shared research outputs
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar

Nithin D. Adappa

University of Pennsylvania

View shared research outputs
Top Co-Authors

Avatar

Jason G. Newman

University of Pennsylvania

View shared research outputs
Top Co-Authors

Avatar
Top Co-Authors

Avatar

David Mathieu

Université de Sherbrooke

View shared research outputs
Top Co-Authors

Avatar

Hideyuki Kano

University of Pittsburgh

View shared research outputs
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Researchain Logo
Decentralizing Knowledge