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Darryl Lau and Dean Chou

OBJECT

Spinal metastases most commonly affect the vertebral bodies of the spinal column, and spinal cord compression is an indication for surgery. Commonly, an open posterior approach is employed to perform a transpedicular costotransversectomy or lateral extracavitary corpectomy. Because of the short life expectancies in patients with metastatic spinal disease, decreasing the morbidity of surgical treatment and recovery time is critical. One potential approach to decreasing morbidity is utilizing minimally invasive surgery (MIS). Although significant advances have been made in MIS of the spine, data supporting the utility of MIS are still emerging. This study compared outcomes of patients who underwent mini-open versus traditional open transpedicular corpectomy for spinal metastases in the thoracic spine.

METHODS

A consecutive cohort from 2006 to 2013 of 49 adult patients who underwent thoracic transpedicular corpectomies for spinal metastases was retrospectively identified. Patients were categorized into one of 2 groups: open surgery and mini-open surgery. Mini-open transpedicular corpectomy was performed with a midline facial incision over only the corpectomy level of interest and percutaneous instrumentation above and below that level. The open procedure consisted of a traditional posterior transpedicular corpectomy. Chi-square test, 2-tailed t-test, and ANOVA models were employed to compare perioperative and follow-up outcomes between the 2 groups.

RESULTS

In the analysis, there were 21 patients who had mini-open surgery and 28 patients who had open surgery. The mean age was 57.9 years, and 59.2% were male. The tumor types encountered were lung (18.3%), renal/bladder (16.3%), breast (14.3%), hematological (14.3%), gastrointestinal tract (10.2%), prostate (8.2%), melanoma (4.1%), and other/unknown (14.3%). There were no significant intergroup differences in demographics, comorbidities, neurological status (American Spinal Injury Association [ASIA] grade), number of corpectomies performed, and number of levels instrumented. The open group had a mean operative time of 413.6 minutes, and the mini-open group had a mean operative time of 452.4 minutes (p = 0.329). Compared with the open group, the mini-open group had significantly less blood loss (917.7 ml vs 1697.3 ml, p = 0.019) and a significantly shorter hospital stay (7.4 days vs 11.4 days, p = 0.001). There was a trend toward a lower perioperative complication rate in the mini-open group (9.5%) compared with the open group (21.4%), but this was not statistically significant (p = 0.265). At follow-up, there were no significant differences in ASIA grade (p = 0.342), complication rate after the 30-day postoperative period (p = 0.999), or need for surgical revision (p = 0.803). The open approach had a higher overall infection rate of 17.9% compared with that in the mini-open approach of 9.5%, but this was not statistically significant (p = 0.409).

CONCLUSIONS

The mini-open transpedicular corpectomy is associated with less blood loss and shorter hospital stay compared with open transpedicular corpectomy. The mini-open corpectomy also trended toward lower infection and complication rates, but these did not reach statistical significance.

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Darryl Lau and Dean Chou

OBJECTIVE

During the mini-open posterior corpectomy, percutaneous instrumentation without fusion is performed above and below the corpectomy level. In this study, the authors' goal was to compare the perioperative and long-term implant failure rates of patients who underwent nonfused percutaneous instrumentation with those of patients who underwent traditional open instrumented fusion.

METHODS

Adult patients who underwent posterior thoracic corpectomies with cage reconstruction between 2009 and 2014 were identified. Patients who underwent mini-open corpectomy had percutaneous instrumentation without fusion, and patients who underwent open corpectomy had instrumented fusion above and below the corpectomy site. The authors compared perioperative outcomes and rates of implant failure requiring reoperation between the open (fused) and mini-open (unfused) groups.

RESULTS

A total of 75 patients were identified, and 53 patients (32 open and 21 mini-open) were available for followup. The mean patient age was 52.8 years, and 56.6% of patients were male. There were no significant differences in baseline variables between the 2 groups. The overall perioperative complication rate was 15.1%, and there was no significant difference between the open and mini-open groups (18.8% vs 9.5%; p = 0.359). The mean hospital stay was 10.5 days. The open group required a significantly longer stay than the mini-open group (12.8 vs 7.1 days; p < 0.001). Overall implant failure rates requiring reoperation were 1.9% at 6 months, 9.1% at 1 year, and 14.7% at 2 years. There were no significant differences in reoperation rates between the open and mini-open groups at 6 months (3.1% vs 0.0%, p = 0.413), 1 year (10.7% vs 6.2%, p = 0.620), and 2 years (18.2% vs 8.3%, p = 0.438). The overall mean follow-up was 29.2 months.

CONCLUSIONS

These findings suggest that percutaneous instrumentation without fusion in mini-open transpedicular corpectomies offers similar implant failure and reoperation rates as open instrumented fusion as far out as 2 years of follow-up.

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Darryl Lau, Dean Chou and Praveen V. Mummaneni

OBJECT

In the treatment of cervical spondylotic myelopathy (CSM), anterior cervical corpectomy and fusion (ACCF) and anterior cervical discectomy and fusion (ACDF) are effective decompressive techniques. It remains to be determined whether ACCF and ACDF offer equivalent outcomes for multilevel CSM. In this study, the authors compared perioperative, radiographic, and clinical outcomes between 2-level ACCF and 3-level ACDF.

METHODS

Between 2006 and 2012, all patients at the authors' hospital who underwent 2-level ACCF or 3-level ACDF performed by 1 of 2 surgeons were identified. Primary outcomes of interest were sagittal Cobb angle, adjacent-segment disease (ASD) requiring surgery, neck pain measured by visual analog scale (VAS), and Nurick score. Secondary outcomes of interest included estimated blood loss (EBL), length of stay, perioperative complications, and radiographic pseudarthrosis rate. Chi-square tests and 2-tailed Student t-tests were used to compare the 2 groups. A subgroup analysis of patients without posterior spinal fusion (PSF) was also performed.

RESULTS

Twenty patients underwent 2-level ACCF, and 35 patients underwent 3-level ACDF during a 6-year period. Preoperative Nurick scores were higher in the ACCF group (2.1 vs 1.1, p = 0.014), and more patients underwent PSF in the 2-level ACCF group compared with patients in the 3-level ACDF group (60.0% vs 17.1%, p = 0.001). Otherwise there were no significant differences in demographics, comorbidities, and baseline clinical parameters between the 2 groups. Two-level ACCF was associated with significantly higher EBL compared with 3-level ACDF for the anterior stage of surgery (382.2 ml vs 117.9 ml, p < 0.001). Two-level ACCF was also associated with a longer hospital stay compared with 3-level ACDF (7.2 days vs 4.9 days, p = 0.048), but a subgroup comparison of patients without PSF showed no significant difference in length of stay (3.1 days vs 4.4 days for 2-level ACCF vs 3-level ACDF, respectively; p = 0.267). Similarly, there was a trend toward more complications in the 2-level ACCF group (20.0%) than the 3-level ACDF group (5.7%; p = 0.102), but a subgroup analysis that excluded those who had second-stage PSF no longer showed the same trend (2-level ACCF, 0.0% vs 3-level ACDF, 3.4%; p = 0.594). There were no significant differences between the ACCF group and the ACDF group in terms of postoperative sagittal Cobb angle (7.2° vs 12.1°, p = 0.173), operative ASD (6.3% vs 3.6%, p = 0.682), and radiographic pseudarthrosis rate (6.3% vs 7.1%, p = 0.909). Both groups had similar improvement in mean VAS neck pain scores (3.4 vs 3.2 for ACCF vs ACDF, respectively; p = 0.860) and Nurick scores (0.8 vs 0.7, p = 0.925).

CONCLUSIONS

Two-level ACCF was associated with greater EBL and longer hospital stays when patients underwent a second-stage PSF. However, the length of stay was similar when patients underwent anterior-only decompression with either 2-level ACCF or 3-level ACDF. Furthermore, perioperative complication rates were similar in the 2 groups when patients underwent anterior decompression without PSF. Both groups obtained similar postoperative cervical lordosis, operative ASD rates, radiographic pseudarthrosis rates, neurological improvement, and pain relief.

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Darryl Lau, Caleb Rutledge and Manish K. Aghi

OBJECT

Cushing's disease (CD) can lead to significant morbidity secondary to hormonal sequelae or mass effect from the pituitary tumor. A transsphenoidal approach to resection of the adrenocorticotropic hormone (ACTH)–secreting pituitary adenoma is the first-line treatment. However, in the setting in which patients are unable to undergo surgery, have acute hypercortisolism, or have recurrent disease, medical therapy can play an important role. The authors performed a systematic review to highlight the efficacy of medical treatment of CD and discuss novel molecular insights that could guide the development of future medical treatments of CD.

METHODS

A search on current medical therapies for CD was performed. After individual medical therapeutic agents for CD were identified, each agent underwent a formal systematic search. The phrase “(name of agent) and Cushing's” was used as a search term in PubMed for all years up to 2014. The abstract of each article was reviewed for studies that evaluated the efficacy of medical treatment of CD. Only studies that enrolled at least 20 patients were included in the review.

RESULTS

A total of 11 articles on 6 individual agents were included in this review. Specific medical therapies were categorized based on the level of action: pituitary directed (cabergoline and pasireotide), adrenal/steroidogenesis directed (ketoconazole, metyrapone, and mitotane), and end-tissue directed/cortisol receptors (mifepristone). The studies identified consisted of a mix of retrospective reviews and small clinical trials. Only pasireotide and mifepristone have undergone Phase III clinical trials, from which they garnered FDA approval for the treatment of patients with CD. Overall, agents targeting ACTH secretion and steroidogenesis were found to be quite effective in reducing urine free cortisol (UFC) to levels near normal. A significant reduction in UFC was observed in 45%–100% of patients and a majority of patients gained clinical improvement. Similarly, inhibition at the end-tissue level led to clinical improvement in 87% of patients. However, side-effect rates associated with these drugs are high (up to 88%). Ketoconazole has been shown to enhance tumor appearance on MRI to facilitate pituitary resection. Promising molecular targets have been identified, including epidermal growth factor receptor, retinoic acid receptors, and cyclin dependent kinases. These pathways have been linked to the regulation of pro-opiomelanocortin expression, ACTH secretion, and tumor growth.

CONCLUSIONS

Despite encouraging Phase III clinical trials leading to FDA approval of 2 agents for treatment of patients with CD, no agent has yet produced results comparable to resection. As a result, the molecular insights gained into CD pathogenesis will need to continue to be expanded until they can lead to the development of medical therapies for CD with a favorable side-effect profile and efficacy comparable to resection. Ideally these agents should also reduce tumor size, which could potentially permit their eventual discontinuation.

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Ramin A. Morshed, Seunggu J. Han, Darryl Lau and Mitchel S. Berger

Surgery guided by 5-aminolevulinic acid (ALA) fluorescence has become a valuable adjunct in the resection of malignant intracranial gliomas. Furthermore, the fluorescence intensity of biopsied areas of a resection cavity correlates with histological identification of tumor cells. However, in the case of lesions deep within a resection cavity, light penetration may be suboptimal, resulting in less excitation of 5-ALA metabolites, leading to decreased fluorescence emission. To address this obstacle, the authors report on the use of a 400-nm wavelength fiber-optic lighted suction instrument that can be used both during resection of a tumor and to provide direct light to deeper areas of a resection cavity. In the presented case, this wavelength-specific lighted suction instrument improved the fluorescence intensity of patches of malignant tissue within the resection cavity. This technique may further improve the utility of 5-ALA in identifying tumor-infiltrated tissue for deep-seated lesions. Additionally, this tool may have implications for scoring systems that correlate 5-ALA fluorescence intensity with histological identification of malignant cells.

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Darryl Lau, Mitchel S. Berger, Dhruv Khullar and John Maa

Cigarette smoking is a common health risk behavior among the general adult population, and is the leading preventable cause of morbidity and mortality in the US. The surgical literature shows that active tobacco smoking is a major risk factor for perioperative morbidity and complications, and that preoperative smoking cessation is an effective measure to lower these risks associated with active smoking. However, few studies have examined the effects of smoking and perioperative complications following neurosurgical procedures. The goal of this review was to highlight the scientific data that do exist regarding the impact of smoking on neurosurgical outcomes, to promote awareness of the need for further work in the specific neurosurgical context, and to suggest ways that neurosurgeons can promote smoking cessation in their patients and lead efforts nationally to emphasize the importance of preoperative smoking cessation. This review indicates that there is limited but good evidence that smoking is associated with higher rates of perioperative complications following neurosurgical intervention. Specific research is needed to understand the effects of smoking and perioperative complications. Neurosurgeons should encourage preoperative smoking cessation as part of their clinical practice to mitigate perioperative morbidity associated with active smoking.

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Darryl Lau, Andrew K. Chan, Vedat Deverin and Christopher P. Ames

OBJECTIVE

Adult spinal deformity (ASD) develops in the setting of asymmetrical arthritic degeneration, and can also be due to iatrogenic causes, such as prior surgery. Many patients who present with ASD have undergone prior spine surgery with instrumentation. Unfortunately, contemporary studies that evaluate the effect of prior surgery or instrumentation on perioperative outcomes, readmission rates, and need for reoperation are lacking.

METHODS

All ASD patients who underwent a 3-column osteotomy performed by the senior author at the authors’ institution for correction of thoracolumbar spinal deformity between 2006 and 2016 were identified. The authors compared surgical outcomes between primary (first-time) and revision cases. Further subgroup analysis was conducted to investigate the effect of the number of prior surgeries (0, 1, 2, 3, 4, and 5 or more) and the presence of spinal instrumentation on outcomes. Multivariate analysis was used to adjust for relevant and significant confounders.

RESULTS

A total of 300 patients were included; 38.3% of patients were male. The overall perioperative complication rate was 24.7%, and the mean length of hospitalization was 8.2 days. The 90-day readmission rate was 9.0%, and the overall follow-up reoperation rate was 26.7%. There were no significant differences in complication rates (26.6% vs 24.0%, p = 0.645), length of hospitalization (8.7 vs 7.9 days, p = 0.229), readmission rates (11.4% vs 8.1%, p = 0.387), or reoperation rates (26.6% vs 26.7%, p = 0.984) between primary and revision cases. There was no significant difference in wound complications (infections/dehiscence) requiring reoperation (5.1% vs 6.3%, p = 0.683). Subgroup analysis conducted to evaluate the effect of the number of prior spinal surgeries or the presence of spinal instrumentation did not reveal significant differences for the aforementioned surgical outcomes. In adjusted multivariate analysis, there were no significant associations between history of prior surgery (number of prior surgeries and prior instrumentation) and all of the surgical outcomes of interest.

CONCLUSIONS

The findings from this study suggest that patients who have undergone prior spine surgery with or without instrumentation are not at increased risk for perioperative complications, need for readmission, or reoperation following 3-column osteotomy of the thoracolumbar spine.

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Daniel C. Lu, Darryl Lau, Jasmine G. Lee and Dean Chou

Object

Whereas standard anterior approaches for thoracolumbar corpectomies have commonly been used, the transpedicular technique is increasingly used to perform corpectomies from a posterior approach. The authors conducted a study to analyze whether there was a difference in outcomes by comparing transpedicular corpectomies to standard anterior thoracolumbar corpectomies.

Methods

The senior author performed thoracolumbar corpectomies in 80 patients between 2004 and 2008. The authors reviewed medical records and follow-up data, consisting of clinic visits, radiographs, or telephone interviews. Neurological outcome, complications, operative times, revision surgery rates, and estimated blood loss (EBL) were evaluated.

Results

Thirty-four patients underwent transpedicular corpectomies, and 46 patients underwent anterior thoracolumbar approaches. Single-level transpedicular corpectomies appear to be comparable to anterior-only corpectomies in terms of EBL, operative time, and complication rates. There was a higher complication rate, increased EBL, and longer operative time with anterior-posterior corpectomies compared with transpedicular corpectomies. Patients undergoing transpedicular corpectomies had a greater recovery of neurological function than those in whom anterior-approach corpectomies were performed.

Conclusions

The transpedicular corpectomy appears to have a comparable morbidity rate to anterior-only corpectomies, but its morbidity rate is lower than that of anterior-posterior corpectomies.

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Darryl Lau, Shawn L. Hervey-Jumper, Seunggu J. Han and Mitchel S. Berger

OBJECTIVE

There is ample evidence that extent of resection (EOR) is associated with improved outcomes for glioma surgery. However, it is often difficult to accurately estimate EOR intraoperatively, and surgeon accuracy has yet to be reviewed. In this study, the authors quantitatively assessed the accuracy of intraoperative perception of EOR during awake craniotomy for tumor resection.

METHODS

A single-surgeon experience of performing awake craniotomies for tumor resection over a 17-year period was examined. Retrospective review of operative reports for quantitative estimation of EOR was recorded. Definitive EOR was based on postoperative MRI. Analysis of accuracy of EOR estimation was examined both as a general outcome (gross-total resection [GTR] or subtotal resection [STR]), and quantitatively (5% within EOR on postoperative MRI). Patient demographics, tumor characteristics, and surgeon experience were examined. The effects of accuracy on motor and language outcomes were assessed.

RESULTS

A total of 451 patients were included in the study. Overall accuracy of intraoperative perception of whether GTR or STR was achieved was 79.6%, and overall accuracy of quantitative perception of resection (within 5% of postoperative MRI) was 81.4%. There was a significant difference (p = 0.049) in accuracy for gross perception over the 17-year period, with improvement over the later years: 1997–2000 (72.6%), 2001–2004 (78.5%), 2005–2008 (80.7%), and 2009–2013 (84.4%). Similarly, there was a significant improvement (p = 0.015) in accuracy of quantitative perception of EOR over the 17-year period: 1997–2000 (72.2%), 2001–2004 (69.8%), 2005–2008 (84.8%), and 2009–2013 (93.4%). This improvement in accuracy is demonstrated by the significantly higher odds of correctly estimating quantitative EOR in the later years of the series on multivariate logistic regression. Insular tumors were associated with the highest accuracy of gross perception (89.3%; p = 0.034), but lowest accuracy of quantitative perception (61.1% correct; p < 0.001) compared with tumors in other locations. Even after adjusting for surgeon experience, this particular trend for insular tumors remained true. The absence of 1p19q co-deletion was associated with higher quantitative perception accuracy (96.9% vs 81.5%; p = 0.051). Tumor grade, recurrence, diagnosis, and isocitrate dehydrogenase-1 (IDH-1) status were not associated with accurate perception of EOR. Overall, new neurological deficits occurred in 8.4% of cases, and 42.1% of those new neurological deficits persisted after the 3-month follow-up. Correct quantitative perception was associated with lower postoperative motor deficits (2.4%) compared with incorrect perceptions (8.0%; p = 0.029). There were no detectable differences in language outcomes based on perception of EOR.

CONCLUSIONS

The findings from this study suggest that there is a learning curve associated with the ability to accurately assess intraoperative EOR during glioma surgery, and it may take more than a decade to be truly proficient. Understanding the factors associated with this ability to accurately assess EOR will provide safer surgeries while maximizing tumor resection.

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Darryl Lau, Stephen T. Magill and Manish K. Aghi

Object

Glioblastoma is the most aggressive and diffusely infiltrative primary brain tumor. Recurrence is expected and is extremely difficult to treat. Over the past decade, the accumulation of knowledge regarding the molecular and genetic profile of glioblastoma has led to numerous molecularly targeted therapies. This article aims to review the literature and highlight the mechanisms and efficacies of molecularly targeted therapies for recurrent glioblastoma.

Methods

A systematic search was performed with the phrase “(name of particular agent) and glioblastoma” as a search term in PubMed to identify all articles published up until 2014 that included this phrase in the title and/or abstract. The references of systematic reviews were also reviewed for additional sources. The review included clinical studies that comprised at least 20 patients and reported results for the treatment of recurrent glioblastoma with molecular targeted therapies.

Results

A total of 42 articles were included in this review. In the treatment of recurrent glioblastoma, various targeted therapies have been tested over the past 10–15 years. The targets of interest include epidermal growth factor receptor, vascular endothelial growth factor receptor, platelet-derived growth factor receptor, Ras pathway, protein kinase C, mammalian target of rapamycin, histone acetylation, and integrins. Unfortunately, the clinical responses to most available targeted therapies are modest at best. Radiographic responses generally range in the realm of 5%–20%. Progression-free survival at 6 months and overall survival were also modest with the majority of studies reporting a 10%–20% 6-month progression-free survival and 5- to 8-month overall survival. There have been several clinical trials evaluating the use of combination therapy for molecularly targeted treatments. In general, the outcomes for combination therapy tend to be superior to single-agent therapy, regardless of the specific agent studied.

Conclusions

Recurrent glioblastoma remains very difficult to treat, even with molecular targeted therapies and anticancer agents. The currently available targeted therapy regimens have poor to modest activity against recurrent glioblastoma. As newer agents are actively being developed, combination regimens have provided the most promising results for improving outcomes. Targeted therapies matched to molecular profiles of individual tumors are predicted to be a critical component necessary for improving efficacy in future trials.