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Ana Rodríguez-Hernández, Christina Huang and Michael T. Lawton

Iatrogenic pseudoaneurysms are rare but serious complications of transsphenoidal surgery, and an iatrogenic pseudoaneurysm of the posterior cerebral artery (PCA) has been reported just once in the literature. The authors encountered such a case with a new P1 segment PCA pseudoaneurysm after endoscopic transsphenoidal resection of a pituitary adenoma. The aneurysm proved ideal for a novel intracranial–intracranial bypass in which the superior cerebellar artery (SCA) was used as an in situ donor artery to revascularize the recipient P2 segment. The bypass allowed aneurysm trapping without causing ischemic stroke or neurological morbidity. This case represents the first reported surgical treatment of an iatrogenic PCA pseudoaneurysm. Endovascular occlusion with coils was an option, but dolichoectatic morphology requires sacrifice of the P1 segment, with associated risks to the thalamoperforators and circumflex perforators. The SCA-PCA bypass was ideal because of low-flow demands. Like other in situ bypasses, it requires no dissection of extracranial arteries, no second incision for harvesting interposition grafts, and has a high likelihood of long-term patency. The SCA-PCA bypass is also applicable to fusiform SCA aneurysms requiring revascularization with trapping. This case demonstrates a dangerous complication that results from the limited view of the posterolateral surgical field through the endoscope and the imprecision of endoscopic instruments.

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R. Michael Scott

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Lijun Ma, Lynn Verhey, Cynthia Chuang, Martina Descovich, Vernon Smith, Kim Huang, Michael McDermott and Penny Sneed

Object

The new capability of composite sector collimation in Gamma Knife Perfexion produces complex, nonspherical, and nonelliptical dose distributions. In this study, the authors investigated the effect of composite sector collimation on average dose fall-off compared with the previous Gamma Knife model.

Methods

A general formalism was derived to describe the peripheral dose distribution of all Gamma Knife models in the form of (V/V0) = (D/D0)γ, where V is the volume of the peripheral isodose line with the value of D, V0 is the reference prescription isodose volume, D0 is the prescription dose, and γ is the fitting parameter that determines how fast the dose falls off near the target. Based on this formula, the authors compared 40 cases involving patients treated with Gamma Knife Perfexion with 40 similar cases involving patients treated with Gamma Knife model 4C. The cases were grouped based on the use of the sector collimators in the treatment planning process. For each group as well as all cases combined, the mean γ values were compared by means of the Student t-test for varying ranges of the peripheral dose distribution—from 100% of the prescription dose to 75, 50, and 25% of the prescription dose.

Results

The fit of general formula to the data was excellent for both Gamma Knife Perfexion and Gamma Knife 4C with R2> 0.99 for all the cases. The overall γ values (mean ± 2 standard deviations) were as follows: γ = −1.74 ± 0.47 (Model 4C) versus −1.77 ± 0.40 (Perfexion) within 100–75% of the prescription dose; γ = −1.57 ± 0.26 (Model 4C) versus −1.58 ± 0.25 (Perfexion) within 100–50% of the prescription dose; γ = −1.47 ± 0.18 (Model 4C) versus −1.50 ± 0.16 (Perfexion) within 100–25% of the prescription dose. No statistical significance between the mean differences for Gamma Knife Perfexion and Model 4C was found within these ranges. The probability values were 0.65, 0.84, and 0.22, respectively.

Conclusions

The use of composite sector collimators in Gamma Knife Perfexion demonstrated no statistically significant effects on the volume-averaged dose fall-off near a target periphery for typical treatment cases.

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Peigen Huang, Ayman Allam, Alphonse Taghian, Jill Freeman, Michael Duffy and Herman D. Suit

✓ The growth and metastatic behavior of five human glioblastoma multiforme xenografts and nine human xenografts of various histological types were compared in severe combined immunodeficient (SCID) mice. The results demonstrate that the metastatic behavior of the human glioblastoma multiforme xenografts did not differ significantly from a variety of other histological xenografts when evaluated at the same transplantation site in the SCID model. These results are consistent with the hypothesis that the site of glioblastoma multiforme growth influences the extraneural metastatic spread of this disease and lead the authors to suggest that the clinical rarity of distant metastasis is not a fundamental property of these cells. A total of 340 male 7- to 8-week-old SCID mice received subcutaneous transplantation of tumor fragments (21–25 mice per tumor type). The tumor-bearing leg was amputated when the tumor reached a volume of 500 mm3; mice were observed for up to 5 months. There was a trend for a lower take rate, longer latent period, longer volume doubling time (VDT) and growth time (GT) in glioblastoma multiforme as opposed to carcinoma and soft tissue sarcoma xenografts. The highest local recurrence rates (78% and 68%) were observed in two glioblastomas multiforme. Both the glioblastoma multiforme and the other histological xenografts exhibited a widely varying metastatic rate: no correlation was demonstrated between VDT, GT, local control/recurrence, and distant metastasis. These findings show SCID mice to be an attractive model for further biological and preclinical studies of human glioblastoma multiforme.

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Michael Karsy, Jian Guan and L. Eric Huang

OBJECTIVE

Gliomas are one of the most common types of primary brain tumors. Recent studies have supported the importance of key genetic alterations, including isocitrate dehydrogenase (IDH) mutations and 1p19q codeletion, in glioma prognosis. Mutant IDH produces 2-hydroxyglutarate from α-ketoglutarate, a key metabolite of the Krebs cycle. The mitochondrial pyruvate carrier (MPC) is composed of MPC1 and MPC2 subunits and is functionally essential for the Krebs cycle. The authors sought to explore the impact of MPC1 and MPC2 expression on patient prognosis.

METHODS

Genomic and clinical data in patients with lower-grade glioma (WHO grades II and III) from The Cancer Genome Atlas (TCGA) were evaluated using Kaplan-Meier analysis and hazards modeling. Validation was conducted with additional data sets, including glioblastoma.

RESULTS

A total of 286 patients with lower-grade glioma (mean age 42.7 ± 13.5 years, 55.6% males) included 54 cases of IDH–wild type (18.9%); 140 cases of IDH-mutant, 1p19q-intact (49.0%); and 85 cases of IDH-mutant, 1p19q-codeleted (29.7%) tumors. Kaplan-Meier analysis showed that an MPC1 z-score > 0 distinguished better survival, particularly in IDH-mutant (p < 0.01) but not IDH–wild type tumors. Conversely, an MPC2 z-score > 0 identified worsened survival, particularly in IDH-mutant (p < 0.01) but not IDH–wild type tumors. Consistently, neither MPC1 nor MPC2 was predictive in a glioblastoma data set containing 5% IDH-mutant cases. Within the IDH-stratified lower-grade glioma data set, MPC1 status distinguished improved survival in 1p19q-codeleted tumors (p < 0.05), whereas MPC2 expression delineated worsened survival in 1p19q-intact tumors (p < 0.01). A hazards model identified IDH and 1p19q status, age (p = 0.01, HR = 1.03), Karnofsky Performance Scale (KPS) score (p = 0.03, HR = 0.97), and MPC1 (p = 0.003, HR = 0.52) but not MPC2 (p = 0.38) as key variables affecting overall survival. Further validation confirmed MPC1 as an independent predictor of lower-grade glioma. A clinical risk score using IDH and 1p19q status, age, KPS score, and MPC1 and MPC2 z-scores defined 4 risk categories for lower-grade glioma; this score was validated using a secondary glioma data set.

CONCLUSIONS

These results support the importance of MPC, especially MPC1, in improving prognostication of IDH-mutant tumors. The generation of a risk score system directly translates this finding to clinical application; however, further research to improve the molecular understanding of the role of MPC in the metabologenomic regulation of gliomas is warranted.

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Sam Q. Sun, Ammar H. Hawasli, Jiayi Huang, Michael R. Chicoine and Albert H. Kim

The management of WHO Grade II “atypical” meningiomas (AMs) and Grade III “malignant” meningiomas (MMs) remains controversial and under-investigated in prospective studies. The roles of surgery, radiation therapy, radiosurgery, and chemotherapy have been incompletely delineated. This has left physicians to decipher how they should treat patients on a case-by-case basis. In this study, the authors review the English-language literature on the management and clinical outcomes associated with AMs and MMs diagnosed using the WHO 2000/2007 grading criteria. Twenty-two studies for AMs and 7 studies for MMs were examined in detail. The authors examined clinical decision points using the literature and concepts from evidence-based medicine. Acknowledging the retrospective nature of the studies concerning AM and MM, the authors did find evidence for the following clinical strategies: 1) maximal safe resection of AM and MM; 2) active surveillance after gross-total resection of AM; 3) adjuvant radiation therapy after subtotal resection of AM, especially in the absence of putative radioresistant features; and 4) adjuvant radiation therapy after resection of MM.

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Laura B. Ngwenya, Catherine G. Suen, Phiroz E. Tarapore, Geoffrey T. Manley and Michael C. Huang

OBJECTIVE

Blood loss and moderate anemia are common in patients with traumatic brain injury (TBI). However, despite evidence of the ill effects and expense of the transfusion of packed red blood cells, restrictive transfusion practices have not been universally adopted for patients with TBI. At a Level I trauma center, the authors compared patients with TBI who were managed with a restrictive (target hemoglobin level > 7 g/dl) versus a liberal (target hemoglobin level > 10 g/dl) transfusion protocol. This study evaluated the safety and cost-efficiency of a hospital-wide change to a restrictive transfusion protocol.

METHODS

A retrospective analysis of patients with TBI who were admitted to the intensive care unit (ICU) between January 2011 and September 2015 was performed. Patients < 16 years of age and those who died within 24 hours of admission were excluded. Demographic data and injury characteristics were compared between groups. Multivariable regression analyses were used to assess hospital outcome measures and mortality rates. Estimates from an activity-based cost analysis model were used to detect changes in cost with transfusion protocol.

RESULTS

A total of 1565 patients with TBI admitted to the ICU were included in the study. Multivariable analysis showed that a restrictive transfusion strategy was associated with fewer days of fever (p = 0.01) and that patients who received a transfusion had a larger fever burden. ICU length of stay, ventilator days, incidence of lung injury, thromboembolic events, and mortality rates were not significantly different between transfusion protocol groups. A restrictive transfusion protocol saved approximately $115,000 annually in hospital direct and indirect costs.

CONCLUSIONS

To the authors’ knowledge, this is the largest study to date to compare transfusion protocols in patients with TBI. The results demonstrate that a hospital-wide change to a restrictive transfusion protocol is safe and cost-effective in patients with TBI.

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Ali Tayebi Meybodi, Wendy Huang, Arnau Benet, Olivia Kola and Michael T. Lawton

OBJECT

Management of complex aneurysms of the middle cerebral artery (MCA) can be challenging. Lesions not amenable to endovascular techniques or direct clipping might require a bypass procedure with aneurysm obliteration. Various bypass techniques are available, but an algorithmic approach to classifying these lesions and determining the optimal bypass strategy has not been developed. The objective of this study was to propose a comprehensive and flexible algorithm based on MCA aneurysm location for selecting the best of multiple bypass options.

METHODS

Aneurysms of the MCA that required bypass as part of treatment were identified from a large prospectively maintained database of vascular neurosurgeries. According to its location relative to the bifurcation, each aneurysm was classified as a prebifurcation, bifurcation, or postbifurcation aneurysm.

RESULTS

Between 1998 and 2015, 30 patients were treated for 30 complex MCA aneurysms in 8 (27%) prebifurcation, 5 (17%) bifurcation, and 17 (56%) postbifurcation locations. Bypasses included 8 superficial temporal artery–MCA bypasses, 4 high-flow extracranial-to-intracranial (EC-IC) bypasses, 13 IC-IC bypasses (6 reanastomoses, 3 reimplantations, 3 interpositional grafts, and 1 in situ bypass), and 5 combination bypasses. The bypass strategy for prebifurcation aneurysms was determined by the involvement of lenticulostriate arteries, whereas the bypass strategy for bifurcation aneurysms was determined by rupture status. The location of the MCA aneurysm in the candelabra (Sylvian, insular, or opercular) determined the bypass strategy for postbifurcation aneurysms. No deaths that resulted from surgery were found, bypass patency was 90%, and the condition of 90% of the patients was improved or unchanged at the most recent follow-up.

CONCLUSIONS

The bypass strategy used for an MCA aneurysm depends on the aneurysm location, lenticulostriate anatomy, and rupture status. A uniform bypass strategy for all MCA aneurysms does not exist, but the algorithm proposed here might guide selection of the optimal EC-IC or IC-IC bypass technique.

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Michael G. Fehlings and Jefferson R. Wilson

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Raqeeb Haque, Teresa J. Wojtasiewicz, Paul R. Gigante, Mark A. Attiah, Brendan Huang, Steven R. Isaacson and Michael B. Sisti

Object

The goal of this article was to show that a combination of facial nerve–sparing microsurgical resection and Gamma Knife surgery (GKS) for expansion of any residual tumor can preserve good facial nerve function in patients with recurrent vestibular schwannoma (VS).

Methods

Records of individuals treated by a single surgeon with a facial nerve–sparing technique for a VS between 1998 and 2009 were retrospectively analyzed for tumor recurrence. Of the 383 patients treated for VS, 151 underwent microsurgical resection, and 20 (13.2%) of these patients required postoperative retreatment for a significant expansion of residual tumor after microsurgery. These 20 patients were re-treated with GKS.

Results

The rate of preservation of good facial nerve function (Grade I or II on the House-Brackmann scale) in patients treated with microsurgery for VS was 97%. Both subtotal and gross-total resection had excellent facial nerve preservation rates (97% vs 96%), although subtotal resection carried a higher risk that patients would require retreatment. In patients re-treated with GKS after microsurgery, the rate of facial nerve preservation was 95%.

Conclusions

In patients with tumors that cannot be managed with radiosurgery alone, a facial nerve–sparing resection followed by GKS for any significant regrowth provides excellent facial nerve preservation rates.