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Surgical Resection and Interstitial Iodine-125 Brachytherapy for High-Grade Meningiomas: A 25-Year Series

Magill, Stephen T; Lau, Darryl; Raleigh, David R; Sneed, Penny K; Fogh, Shannon E; McDermott, Michael W
BACKGROUND:Atypical and malignant meningiomas can recur despite resection and radiation. OBJECTIVE:To determine outcomes of patients with recurrent atypical or malignant meningioma treated with repeat resection and permanent iodine-125 ( 125 I) brachy-therapy. METHODS:Charts of patients who underwent surgical resection and 125 I brachyther-apy implantation for atypical and malignant meningiomas between 1988 and 2013 were retrospectively reviewed. The Kaplan-Meier actuarial method was used to calculate progression-free and overall survival. The log-rank test was used to compare groups. Significance was set at P < .05. RESULTS:Forty-two patients underwent 50 resections with 125 I brachytherapy im-plantations. All patients had undergone previous resections and 85% had previously undergone radiation. Median follow-up was 7.5 years after diagnosis and 2.3 years after brachytherapy. Median time to progression after resection with 125 I brachytherapy was 20.9 months for atypical meningioma, 11.4 months for malignant meningioma, and 11.4 months for the combined groups. Median survival after re-resection and 125 I brachytherapy was 3.5 years for atypical meningioma, 2.3 years for malignant menin-gioma, and 3.3 years for all subjects. Median overall survival after diagnosis was 11.1 years for atypical meningioma, 9.1 years for malignant meningioma, and 9.4 years for all subjects. Complications occurred in 17 patients and included radiation necrosis (n = 8, 16%), wound breakdown (n = 6, 12%), hydrocephalus (n = 4, 8%), infection (n = 3, 6%), and a pseudomeningocele (n = 2, 5%). CONCLUSION:This is the largest experience with adjuvant 125 I brachytherapy for recurrent high-grade meningiomas. The outcomes support the use of adjuvant brachytherapy as an option for these aggressive tumors.
PMID: 27258768
ISSN: 1524-4040
CID: 4618232

Stereotactic probability and variability of speech arrest and anomia sites during stimulation mapping of the language dominant hemisphere

Chang, Edward F; Breshears, Jonathan D; Raygor, Kunal P; Lau, Darryl; Molinaro, Annette M; Berger, Mitchel S
OBJECTIVE Functional mapping using direct cortical stimulation is the gold standard for the prevention of postoperative morbidity during resective surgery in dominant-hemisphere perisylvian regions. Its role is necessitated by the significant interindividual variability that has been observed for essential language sites. The aim in this study was to determine the statistical probability distribution of eliciting aphasic errors for any given stereotactically based cortical position in a patient cohort and to quantify the variability at each cortical site. METHODS Patients undergoing awake craniotomy for dominant-hemisphere primary brain tumor resection between 1999 and 2014 at the authors' institution were included in this study, which included counting and picture-naming tasks during dense speech mapping via cortical stimulation. Positive and negative stimulation sites were collected using an intraoperative frameless stereotactic neuronavigation system and were converted to Montreal Neurological Institute coordinates. Data were iteratively resampled to create mean and standard deviation probability maps for speech arrest and anomia. Patients were divided into groups with a "classic" or an "atypical" location of speech function, based on the resultant probability maps. Patient and clinical factors were then assessed for their association with an atypical location of speech sites by univariate and multivariate analysis. RESULTS Across 102 patients undergoing speech mapping, the overall probabilities of speech arrest and anomia were 0.51 and 0.33, respectively. Speech arrest was most likely to occur with stimulation of the posterior inferior frontal gyrus (maximum probability from individual bin = 0.025), and variance was highest in the dorsal premotor cortex and the posterior superior temporal gyrus. In contrast, stimulation within the posterior perisylvian cortex resulted in the maximum mean probability of anomia (maximum probability = 0.012), with large variance in the regions surrounding the posterior superior temporal gyrus, including the posterior middle temporal, angular, and supramarginal gyri. Patients with atypical speech localization were far more likely to have tumors in canonical Broca's or Wernicke's areas (OR 7.21, 95% CI 1.67-31.09, p < 0.01) or to have multilobar tumors (OR 12.58, 95% CI 2.22-71.42, p < 0.01), than were patients with classic speech localization. CONCLUSIONS This study provides statistical probability distribution maps for aphasic errors during cortical stimulation mapping in a patient cohort. Thus, the authors provide an expected probability of inducing speech arrest and anomia from specific 10-mm2 cortical bins in an individual patient. In addition, they highlight key regions of interindividual mapping variability that should be considered preoperatively. They believe these results will aid surgeons in their preoperative planning of eloquent cortex resection.
PMID: 26894457
ISSN: 1933-0693
CID: 4618202

The Mini-Open Pedicle Subtraction Osteotomy for Flat-Back Syndrome and Kyphosis Correction: Operative Technique [Case Report]

Chou, Dean; Lau, Darryl
BACKGROUND:The pedicle subtraction osteotomy (PSO) has been a mainstay treatment for flat-back syndrome. The morbidity of open deformity correction can be high, and minimally invasive applications may reduce such morbidity. OBJECTIVE:To describe an operative technique of the mini-open PSO. METHODS:Two patients underwent percutaneous fixation above and below the PSO, and the PSO was performed in a mini-open fashion. The correction was obtained by cantilever. RESULTS:The patient who underwent the L3 PSO had a prior fusion from T11 to L4 for scoliosis 35 years ago. On presentation at 62 years of age, he had a pelvic incidence of 54°, lumbar lordosis of 23°, sagittal vertical axis of +14 cm, and pelvic tilt of 25°. He underwent an anterior lumbar interbody fusion at L5-S1 followed by a min-open L3 PSO. He had a postoperative lumbar lordosis of 64° (correction of 41°), and his sagittal vertical axis went to +3 cm. His Oswestry Disability Index and visual analog scale scores decreased after surgery. The second patient was 64 years of age and underwent an L1 PSO. He had 43° of kyphosis from T10 to L2. He had a preoperative pelvic incidence of 63°, lumbar lordosis of 35°, pelvic tilt of 24°, and sagittal vertical axis of 3 cm. His postoperative kyphosis improved from 43° to 32°. CONCLUSION:The mini-open PSO can achieve significant lordosis, although it is heavily reliant on anterior arthrodesis. Larger studies are needed to compare this approach with an open PSO.
PMID: 29506275
ISSN: 2332-4260
CID: 4618352

Postoperative Cerebrospinal Fluid Leak Rates with Subfascial Epidural Drain Placement after Intentional Durotomy in Spine Surgery

Niu, Tianyi; Lu, Derek S; Yew, Andrew; Lau, Darryl; Hoffman, Haydn; McArthur, David; Chou, Dean; Lu, Daniel C
Study Design Retrospective chart review. Objective Postoperative cerebrospinal fluid (CSF) leak is a known complication of intraoperative durotomy. Intraoperative placement of subfascial epidural drains following primary dural repair has been proposed as a potential management strategy to prevent formation of CSF cutaneous fistula and symptomatic pseudomeningocele. Here we describe our experience with subfascial drain after intentional durotomy. Methods Medical records of patients who underwent placement of subfascial epidural drains during spinal procedures with intentional intraoperative durotomies over a 4-year period at two institutions were retrospectively reviewed. Primary outcomes of interest were postoperative CSF cutaneous fistula or symptomatic pseudomeningocele formation. Results Twenty-five patients were included. Mean length of follow-up was 9.5 months. Twelve patients (48%) underwent simultaneous arthrodesis. The average duration of the drain was 5.3 days with average daily output of 126.5 mL. Subgroup analyses revealed that average drain duration for the arthrodesis group was 6.33 days, which is significantly greater than that of the nonfused group, which was 3.7 days (p = 0.016). Similarly, the average daily drain output for the arthrodesis subgroup at 153.1 mL was significantly higher than that of the nonfused subgroup (86.8 mL, p = 0.04). No patient developed postoperative CSF cutaneous fistula or symptomatic pseudomeningocele or had negative sequelae associated with overdrainage of CSF. One patient had a delayed wound infection. Conclusions The intraoperative placement of subfascial epidural drains was not associated with postoperative development of CSF cutaneous fistula, symptomatic pseudomeningocele, overdrainage, or subdural hematoma in the cases reviewed. Subfascial closed wound drain placement is a safe and efficacious management method after intentional spinal durotomies. It is particularly helpful in those who undergo simultaneous arthrodesis, as those patients have statistically higher daily drain output and longer drain durations.
PMCID:5110360
PMID: 27853662
ISSN: 2192-5682
CID: 4618242

Costs and readmission rates for the resection of primary and metastatic spinal tumors: a comparative analysis of 181 patients

Lau, Darryl; Chan, Andrew K; Theologis, Alexander A; Chou, Dean; Mummaneni, Praveen V; Burch, Shane; Berven, Sigurd; Deviren, Vedat; Ames, Christopher
OBJECTIVE Because the surgical strategies for primary and metastatic spinal tumors are different, the respective associated costs and morbidities associated with those treatments likely vary. This study compares the direct costs and 90-day readmission rates between the resection of extradural metastatic and primary spinal tumors. The factors associated with cost and readmission are identified. METHODS Adults (age 18 years or older) who underwent the resection of spinal tumors between 2008 and 2013 were included in the study. Patients with intradural tumors were excluded. The direct costs of index hospitalization and 90-day readmission hospitalization were evaluated. The direct costs were compared between patients who were treated surgically for primary and metastatic spinal tumors. The independent factors associated with costs and readmissions were identified using multivariate analysis. RESULTS A total of 181 patients with spinal tumors were included (63 primary and 118 metastatic tumors). Overall, the mean index hospital admission cost for the surgical management of spinal tumors was $52,083. There was no significant difference in the cost of hospitalization between primary ($55,801) and metastatic ($50,098) tumors (p = 0.426). The independent factors associated with higher cost were male sex (p = 0.032), preoperative inability to ambulate (p = 0.002), having more than 3 comorbidities (p = 0.037), undergoing corpectomy (p = 0.021), instrumentation greater than 7 levels (p < 0.001), combined anterior-posterior approach (p < 0.001), presence of a perioperative complication (p < 0.001), and longer hospital stay (p < 0.001). The perioperative complication rate was 21.0%. Of this cohort, 11.6% of patients were readmitted within 90 days, and the mean hospitalization cost of that readmission was $20,078. Readmission rates after surgical treatment for primary and metastatic tumors were similar (11.1% vs 11.9%, respectively) (p = 0.880). Prior hospital stay greater than 15 days (OR 6.62, p = 0.016) and diagnosis of lung metastasis (OR 52.99, p = 0.007) were independent predictors of readmission. CONCLUSIONS Primary and metastatic spinal tumors are comparable with regard to the direct costs of the index surgical hospitalization and readmission rate within 90 days. The factors independently associated with costs are related to preoperative health status, type and complexity of surgery, and postoperative course.
PMID: 27129043
ISSN: 1547-5646
CID: 4618222

Economic Impact of Revision Surgery for Proximal Junctional Failure After Adult Spinal Deformity Surgery: A Cost Analysis of 57 Operations in a 10-year Experience at a Major Deformity Center

Theologis, Alexander A; Miller, Liane; Callahan, Matt; Lau, Darryl; Zygourakis, Corinna; Scheer, Justin K; Burch, Shane; Pekmezci, Murat; Chou, Dean; Tay, Bobby; Mummaneni, Praveen; Berven, Sigurd; Deviren, Vedat; Ames, Christopher P
STUDY DESIGN/METHODS:Retrospective cohort analysis. OBJECTIVE:To evaluate the economic impact of revision surgery for proximal junctional failures (PJF) after thoracolumbar fusions for adult spinal deformity (ASD). SUMMARY OF BACKGROUND DATA/BACKGROUND:PJF after fusions for ASD is a major cause of disability. Although clinical sequelae are described, PJF-revision operation costs are incompletely defined. METHODS:Consecutive adults who underwent thoracolumbar fusions for ASD (August, 2003 to January, 2013) were evaluated. Inclusion criteria include construct from pelvis to L2 or above and minimum 6 months follow-up after the index ASD operation. Direct costs (surgical supplies/implants, room/care, pharmacy, services) were identified from medical billing data and calculated for index ASD operations and subsequent surgeries for PJF. Not included in direct cost data were indirect costs, charges, surgeon fees, or revision operations for indications other than PJF (i.e., pseudarthrosis). Patients were compared based on the construct's upper-instrumented vertebra: upper thoracic (UT: T1-6) versus thoracolumbar junction (TLjxn: T9-L2). RESULTS:Of 501 patients, 382 met inclusion criteria. Fifty-one patients [UT:14; TLjxn: 40 at index; average follow-up 32.6 months (6-92 months)] had revisions for PJF, which summed to $3.2 million total direct cost. Average direct cost of index operations for the cohort ($68,294) was significantly greater than PJF-revisions ($55,547). Compared with TLjxn, UT had a significantly higher average cost for index operations ($79,860 vs. $65,868). However, PJF-revision cases were similar in average cost (UT:$60,103; TLjxn:$53,920; P = 0.09). Costs of PJF amounted to an additional 12.1% of the total index surgical cost in 382 patients. CONCLUSION/CONCLUSIONS:Revision operations for PJF after long thoracolumbar fusions for ASD are associated with an average direct cost of $55,547 per case. Revision costs for PJF are similar based on the index procedure's upper-instrumented vertebra level. At a major tertiary center over a 10-year period, PJF came at a very significant economic expense amounting to $3.2 million for 57 cases. LEVEL OF EVIDENCE/METHODS:3.
PMID: 26909838
ISSN: 1528-1159
CID: 4618212

A prospective Phase II clinical trial of 5-aminolevulinic acid to assess the correlation of intraoperative fluorescence intensity and degree of histologic cellularity during resection of high-grade gliomas

Lau, Darryl; Hervey-Jumper, Shawn L; Chang, Susan; Molinaro, Annette M; McDermott, Michael W; Phillips, Joanna J; Berger, Mitchel S
OBJECT There is evidence that 5-aminolevulinic acid (ALA) facilitates greater extent of resection and improves 6-month progression-free survival in patients with high-grade gliomas. But there remains a paucity of studies that have examined whether the intensity of ALA fluorescence correlates with tumor cellularity. Therefore, a Phase II clinical trial was undertaken to examine the correlation of intensity of ALA fluorescence with the degree of tumor cellularity. METHODS A single-center, prospective, single-arm, open-label Phase II clinical trial of ALA fluorescence-guided resection of high-grade gliomas (Grade III and IV) was held over a 43-month period (August 2010 to February 2014). ALA was administered at a dose of 20 mg/kg body weight. Intraoperative biopsies from resection cavities were collected. The biopsies were graded on a 4-point scale (0 to 3) based on ALA fluorescence intensity by the surgeon and independently based on tumor cellularity by a neuropathologist. The primary outcome of interest was the correlation of ALA fluorescence intensity to tumor cellularity. The secondary outcome of interest was ALA adverse events. Sensitivities, specificities, positive predictive values (PPVs), negative predictive values (NPVs), and Spearman correlation coefficients were calculated. RESULTS A total of 211 biopsies from 59 patients were included. Mean age was 53.3 years and 59.5% were male. The majority of biopsies were glioblastoma (GBM) (79.7%). Slightly more than half (52.5%) of all tumors were recurrent. ALA intensity of 3 correlated with presence of tumor 97.4% (PPV) of the time. However, absence of ALA fluorescence (intensity 0) correlated with the absence of tumor only 37.7% (NPV) of the time. For all tumor types, GBM, Grade III gliomas, and recurrent tumors, ALA intensity 3 correlated strongly with cellularity Grade 3; Spearman correlation coefficients (r) were 0.65, 0.66, 0.65, and 0.62, respectively. The specificity and PPV of ALA intensity 3 correlating with cellularity Grade 3 ranged from 95% to 100% and 86% to 100%, respectively. In biopsies without tumor (cellularity Grade 0), 35.4% still demonstrated ALA fluorescence. Of those biopsies, 90.9% contained abnormal brain tissue, characterized by reactive astrocytes, scattered atypical cells, or inflammation, and 8.1% had normal brain. In nonfluorescent (ALA intensity 0) biopsies, 62.3% had tumor cells present. The ALA-associated complication rate among the study cohort was 3.4%. CONCLUSIONS The PPV of utilizing the most robust ALA fluorescence intensity (lava-like orange) as a predictor of tumor presence is high. However, the NPV of utilizing the absence of fluorescence as an indicator of no tumor is poor. ALA intensity is a strong predictor for degree of tumor cellularity for the most fluorescent areas but less so for lower ALA intensities. Even in the absence of tumor cells, reactive changes may lead to ALA fluorescence.
PMID: 26544781
ISSN: 1933-0693
CID: 4618192

The Clinical Correlation of the Hart-ISSG Proximal Junctional Kyphosis Severity Scale With Health-Related Quality-of-life Outcomes and Need for Revision Surgery

Lau, Darryl; Funao, Haruki; Clark, Aaron J; Nicholls, Fred; Smith, Justin; Bess, Shay; Shaffrey, Chris; Schwab, Frank J; Lafage, Virginie; Deviren, Vedat; Hart, Robert; Kebaish, Khaled M; Ames, Christopher P
STUDY DESIGN: Retrospective analysis of prospective data. OBJECTIVE: Evaluate the utility of the Hart-International Spine Study Group proximal junctional kyphosis severity scale (Hart-ISSG PJKSS). SUMMARY OF BACKGROUND DATA: Proximal junctional kyphosis (PJK) and failure (PJF) are well-described complications after long-segment instrumentation. The Hart-ISSG PJKSS was recently developed and incorporates neurological deficit, pain, instrumentation issues, degree of kyphosis, presence of fracture, and level of upper-most instrumented vertebrae. METHODS: All adult spinal deformity patients with PJK or PJF were identified from two academic centers over a 7-year period. Health-related quality-of-life (HRQOL) outcomes were prospectively collected: Oswestry Disability Index (ODI), visual analogue scale (VAS) pain, SF-36 questionnaire, and SRS-30 questionnaire. Patients were retrospectively assigned Hart-ISSG PJKSS scores. Correlation between the Hart-ISSG PJKSS and outcomes was assessed with linear regression, Pearson correlation coefficients, and chi analysis. RESULTS: A total of 184 cases were included; 21.2% were men and mean age was 65.0 years. Weakness and/or myelopathy were present in 11.4% of patients and 88.6% had pain. Instrumentation issues occurred in 44.0% and 64.1% had PJK-associated fractures. PJK occurred in the upper thoracic spine in 21.7% of cases. Mean PJKSS score was 5.9. The Hart-ISSG PJKSS was significantly and strongly associated with ODI (P < 0.001, r = 0.611), VAS pain (P < 0.001, r = 0.676), SRS-30 function (P < 0.001, r = -0.401), SRS-30 mental health (P < 0.001, r = -0.592), SRS-30 self-image (P < 0.001, r = -0.511), SRS-30 satisfaction (P < 0.001, r = -0.531), and SRS-30 pain (P < 0.001, r = -0.445). Higher scores were associated with higher proportion of patients undergoing revision surgery (P < 0.001); scores of 9 to 11 and 12 to 15 underwent revision 96.0% and 100.0% of the time, respectively. CONCLUSION: The Hart-ISSG PJKSS was strongly correlated with validated functional outcomes and higher scores were associated with higher rates of revision surgery. The Hart-ISSG PJKSS may be a useful clinical tool in the treatment of patient with PJK. LEVEL OF EVIDENCE: 3.
PMID: 26641842
ISSN: 1528-1159
CID: 1989452

Surgical assessment of the insula. Part 2: validation of the Berger-Sanai zone classification system for predicting extent of glioma resection

Hervey-Jumper, Shawn L; Li, Jing; Osorio, Joseph A; Lau, Darryl; Molinaro, Annette M; Benet, Arnau; Berger, Mitchel S
OBJECTIVE:Though challenging, maximal safe resection of insular gliomas enhances overall and progression-free survival and deters malignant transformation. Previously published reports have shown that surgery can be performed with low morbidity. The authors previously described a Berger-Sanai zone classification system for insular gliomas. Using a subsequent dataset, they undertook this study to validate this zone classification system for predictability of extent of resection (EOR) in patients with insular gliomas. METHODS:The study population included adults who had undergone resection of WHO Grade II, III, or IV insular gliomas. In accordance with our prior published report, tumor location was classified according to the Berger-Sanai quadrant-style classification system into Zones I through IV. Interobserver variability was analyzed using a cohort of newly diagnosed insular gliomas and independent classification scores given by 3 neurosurgeons at various career stages. Glioma volumes were analyzed using FLAIR and T1-weighted contrast-enhanced MR images. RESULTS:One hundred twenty-nine procedures involving 114 consecutive patients were identified. The study population from the authors' previously published experience included 115 procedures involving 104 patients. Thus, the total experience included 244 procedures involving 218 patients with insular gliomas treated at the authors' institution. The most common presenting symptoms were seizure (68.2%) and asymptomatic recurrence (17.8%). WHO Grade II glioma histology was the most common (54.3%), followed by Grades III (34.1%) and IV (11.6%). The median tumor volume was 48.5 cm(3). The majority of insular gliomas were located in the anterior portion of the insula with 31.0% in Zone I, 10.9% in Zone IV, and 16.3% in Zones I+IV. The Berger-Sanai zone classification system was highly reliable, with a kappa coefficient of 0.857. The median EOR for all zones was 85%. Comparison of EOR between the current and prior series showed no change and Zone I gliomas continue to have the highest median EOR. Short- and long-term neurological complications remain low, and zone classification correlated with short-term complications, which were highest in Zone I and in Giant insular gliomas. CONCLUSIONS:The previously proposed Berger-Sanai classification system is highly reliable and predictive of insular glioma EOR and morbidity.
PMID: 26339856
ISSN: 1933-0693
CID: 4618182

Abdominopelvic hemorrhage: correlation of CT positivity with the subsequent decision to perform blood transfusion

Chong, Suzanne T; Ellis, James H; Cohan, Richard H; Knoepp, Ursula S; Langley, Travis J; Lau, Darryl; Khalatbari, Shokoufeh
The purpose of this study is to determine the role of computed tomography (CT) on the decision to administer blood transfusions in patients with abdominopelvic hemorrhage (trauma, surgery, invasive procedure, and spontaneous) and to determine the clinical parameters most likely to influence the decision to administer blood transfusions in patients with spontaneous abdominopelvic hemorrhage. In this IRB approved and HIPPA compliant study, retrospective analysis was performed on 298 patients undergoing abdominal and pelvic CT for suspected abdominopelvic hemorrhage and the CT reports and electronic medical records were reviewed. Odds ratios and 95% CI were calculated to compare the odds of abdominopelvic hemorrhage and transfusion for categorical and continuous predictors. The presence of abdominopelvic hemorrhage by CT was significantly associated with blood transfusions for trauma patients (p-value <0.0001) only. 106 patients with suspected spontaneous abdominopelvic hemorrhage had the lowest CT positivity rate (n = 23, 21.7%) but the highest blood transfusion rate (n = 62, 58.5%) compared to the patients with abdominopelvic hemorrhage from known preceding causes. In patients with spontaneous abdominopelvic hemorrhage, low hemoglobin and hematocrit levels immediately prior to obtaining the CT study were more predictive for receiving a blood transfusion (p-value <0.0001) than the presence of hemorrhage by CT. CT positivity is strongly correlated with the decision to administer blood transfusions for patients with abdominopelvic hemorrhage from trauma, indicating that CT studies play a significant role in determining the clinical management of trauma patients. For patients with spontaneous abdominopelvic hemorrhage, the decision to transfuse depends not on the CT study but on the patient's hemoglobin and hematocrit levels. CT studies should therefore not be performed for the sole purpose of determining the need for blood transfusion in patients with spontaneous abdominopelvic hemorrhage.
PMID: 25708279
ISSN: 1432-0509
CID: 4618942