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Daniel A. Orringer

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Todd Hollon, Spencer Lewis, Christian W. Freudiger, X. Sunney Xie and Daniel A. Orringer

Despite advances in the surgical management of brain tumors, achieving optimal surgical results and identification of tumor remains a challenge. Raman spectroscopy, a laser-based technique that can be used to nondestructively differentiate molecules based on the inelastic scattering of light, is being applied toward improving the accuracy of brain tumor surgery. Here, the authors systematically review the application of Raman spectroscopy for guidance during brain tumor surgery. Raman spectroscopy can differentiate normal brain from necrotic and vital glioma tissue in human specimens based on chemical differences, and has recently been shown to differentiate tumor-infiltrated tissues from noninfiltrated tissues during surgery. Raman spectroscopy also forms the basis for coherent Raman scattering (CRS) microscopy, a technique that amplifies spontaneous Raman signals by 10,000-fold, enabling real-time histological imaging without the need for tissue processing, sectioning, or staining. The authors review the relevant basic and translational studies on CRS microscopy as a means of providing real-time intraoperative guidance. Recent studies have demonstrated how CRS can be used to differentiate tumor-infiltrated tissues from noninfiltrated tissues and that it has excellent agreement with traditional histology. Under simulated operative conditions, CRS has been shown to identify tumor margins that would be undetectable using standard bright-field microscopy. In addition, CRS microscopy has been shown to detect tumor in human surgical specimens with near-perfect agreement to standard H & E microscopy. The authors suggest that as the intraoperative application and instrumentation for Raman spectroscopy and imaging matures, it will become an essential component in the neurosurgical armamentarium for identifying residual tumor and improving the surgical management of brain tumors.

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Thomas J. Wilson, Daniel A. Orringer, Stephen E. Sullivan and Parag G. Patil

Thoracic vertebral compression fractures are a known complication of generalized tetanus. The authors report the first known case of an L-2 burst fracture leading to cauda equina syndrome, as a result of generalized tetanus.

This 51-year-old man had generalized tetanus with a constellation of symptoms including compartment syndrome requiring fasciotomies, severe axial spasms and spasms of the extremities, autonomic dysreflexia, hypercarbic respiratory failure, and rhabdomyolysis. During the course of his illness, areflexic paraparesis developed in his lower extremities. He was found to have an L-2 burst fracture with retropulsion of a bone fragment resulting in cauda equina syndrome. Operative intervention was undertaken to decompress the cauda equina and stabilize the spine.

The natural progression of tetanus can be complex, with a mixed picture ranging from spasms plus increased tone and reflexes to reduced tone and reflexes as presynaptic nerve terminals become damaged. The authors suggest that all sudden changes in the neurological examination should prompt consideration of diagnostic imaging before attributing such changes to natural progression of the disease.

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Todd Hollon, Vincent Nguyen, Brandon W. Smith, Spencer Lewis, Larry Junck and Daniel A. Orringer

OBJECTIVE

Survival rates and prognostic factors for supratentorial hemispheric ependymomas have not been determined. The authors therefore designed a retrospective study to determine progression-free survival (PFS), overall survival (OS), and prognostic factors for hemispheric ependymomas.

METHODS

The study population consisted of 8 patients from our institution and 101 patients from the literature with disaggregated survival information (n = 109). Patient age, sex, tumor side, tumor location, extent of resection (EOR), tumor grade, postoperative chemotherapy, radiation, time to recurrence, and survival were recorded. Kaplan-Meier survival analyses and Cox proportional hazard models were completed to determine survival rates and prognostic factors.

RESULTS

Anaplastic histology/WHO Grade III tumors were identified in 62% of cases and correlated with older age. Three-, 5-, and 10-year PFS rates were 57%, 51%, and 42%, respectively. Three-, 5-, and 10-year OS rates were 77%, 71%, and 58%, respectively. EOR and tumor grade were identified on both Kaplan-Meier log-rank testing and univariate Cox proportional hazard models as prognostic for PFS and OS. Both EOR and tumor grade remained prognostic on multivariate analysis. Subtotal resection (STR) predicted a worse PFS (hazard ratio [HR] 4.764, p = 0.001) and OS (HR 4.216, p = 0.008). Subgroup survival analysis of patients with STR demonstrated a 5- and 10-year OS of 28% and 0%, respectively. WHO Grade III tumors also had worse PFS (HR 10.2, p = 0.004) and OS (HR 9.1, p = 0.035). Patients with WHO Grade III tumors demonstrated 5- and 10-year OS of 61% and 46%, respectively. Postoperative radiation was not prognostic for PFS or OS.

CONCLUSIONS

A high incidence of anaplastic histology was found in hemispheric ependymomas and was associated with older age. EOR and tumor grade were prognostic factors for PFS and OS on multivariate analysis. STR or WHO Grade III pathology, or both, predicted worse overall prognosis in patients with hemispheric ependymoma.

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Darryl Lau, Dominic H. Moon, Paul Park, Shawn Hervey-Jumper, Paul E. McKeever and Daniel A. Orringer

Malignant peripheral nerve sheath tumors (MPNSTs) are rare, affecting only a small portion of the general population. In many cases, MPNSTs occur in association with neurofibromatosis Type 1 and at times arise secondary to previous radiation therapy (RT). These tumors can be found essentially anywhere a peripheral nerve is present, but they rarely originate primarily from the spinal nerve or cauda equina and cause leptomeningeal spread. This report describes the treatment course of a 43-year-old man with a history of testicular seminoma treated with RT a decade before, who was found to have a large sacral MPNST. The patient underwent complete sacrectomy for gross-total resection. Despite this effort, he was eventually found to have metastatic lesions throughout the spine and brain, ultimately resulting in acute hydrocephalus and death. Biopsy results of these metastatic lesions proved to be characteristic of his original MPNST. The literature is also reviewed and the diagnostic modalities, management strategies, and prognosis of MPNST are discussed.

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Todd C. Hollon, Adish Parikh, Balaji Pandian, Jamaal Tarpeh, Daniel A. Orringer, Ariel L. Barkan, Erin L. McKean and Stephen E. Sullivan

OBJECTIVE

Pituitary adenomas occur in a heterogeneous patient population with diverse perioperative risk factors, endocrinopathies, and other tumor-related comorbidities. This heterogeneity makes predicting postoperative outcomes challenging when using traditional scoring systems. Modern machine learning algorithms can automatically identify the most predictive risk factors and learn complex risk-factor interactions using training data to build a robust predictive model that can generalize to new patient cohorts. The authors sought to build a predictive model using supervised machine learning to accurately predict early outcomes of pituitary adenoma surgery.

METHODS

A retrospective cohort of 400 consecutive pituitary adenoma patients was used. Patient variables/predictive features were limited to common patient characteristics to improve model implementation. Univariate and multivariate odds ratio analysis was performed to identify individual risk factors for common postoperative complications and to compare risk factors with model predictors. The study population was split into 300 training/validation patients and 100 testing patients to train and evaluate four machine learning models using binary classification accuracy for predicting early outcomes.

RESULTS

The study included a total of 400 patients. The mean ± SD patient age was 53.9 ± 16.3 years, 59.8% of patients had nonfunctioning adenomas and 84.7% had macroadenomas, and the mean body mass index (BMI) was 32.6 ± 7.8 (58.0% obesity rate). Multivariate odds ratio analysis demonstrated that age < 40 years was associated with a 2.86 greater odds of postoperative diabetes insipidus and that nonobese patients (BMI < 30) were 2.2 times more likely to develop postoperative hyponatremia. Using broad criteria for a poor early postoperative outcome—major medical and early surgical complications, extended length of stay, emergency department admission, inpatient readmission, and death—31.0% of patients met criteria for a poor early outcome. After model training, a logistic regression model with elastic net (LR-EN) regularization best predicted early postoperative outcomes of pituitary adenoma surgery on the 100-patient testing set—sensitivity 68.0%, specificity 93.3%, overall accuracy 87.0%. The receiver operating characteristic and precision-recall curves for the LR-EN model had areas under the curve of 82.7 and 69.5, respectively. The most important predictive variables were lowest perioperative sodium, age, BMI, highest perioperative sodium, and Cushing’s disease.

CONCLUSIONS

Early postoperative outcomes of pituitary adenoma surgery can be predicted with 87% accuracy using a machine learning approach. These results provide insight into how predictive modeling using machine learning can be used to improve the perioperative management of pituitary adenoma patients.

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Daniel Orringer, Darryl Lau, Sameer Khatri, Grettel J. Zamora-Berridi, Kathy Zhang, Chris Wu, Neeraj Chaudhary and Oren Sagher

Object

The extent of resection (EOR) is a known prognostic factor in patients with glioblastoma. However, gross-total resection (GTR) is not always achieved. Understanding the factors that prevent GTR is helpful in surgical planning and when counseling patients. The goal of this study was to identify demographic, tumor-related, and technical factors that influence EOR and to define the relationship between the surgeon's impression of EOR and radiographically determined EOR.

Methods

The authors performed a retrospective review of the electronic medical records to identify all patients who underwent craniotomy for glioblastoma resection between 2006 and 2009 and who had both preoperative and postoperative MRI studies. Forty-six patients were identified and were included in the study. Image analysis software (FIJI) was used to perform volumetric analysis of tumor size and EOR based on preoperative and postoperative MRI. Using multivariate analysis, the authors assessed factors associated with EOR and residual tumor volume. Perception of resectability was described using bivariate statistics, and survival was described using the log-rank test and Kaplan-Meier curves.

Results

The EOR was less for tumors in eloquent areas (p = 0.014) and those touching ventricles (p = 0.031). Left parietal tumors had significantly greater residual volume (p = 0.042). The average EOR was 91.0% in this series. There was MRI-demonstrable residual tumor in 69.6% of cases (16 of 23) in which GTR was perceived by the surgeon. Expert reviewers agreed that GTR could be safely achieved in 37.0% of patients (17 of 46) in this series. Among patients with safely resectable tumors, radiographically complete resection was achieved in 23.5% of patients (4 of 17). An EOR greater than 90% was associated with a significantly greater 1-year survival (76.5%) than an EOR less than 90% (p = 0.005).

Conclusions

The authors' findings confirm that tumor location affects EOR and suggest that EOR may also be influenced by the surgeon's ability to judge the presence of residual tumor during surgery. The surgeon's ability to judge completeness of resection during surgery is commonly inaccurate. The authors' study confirms the impact of EOR on 1-year survival.