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Debraj Mukherjee and Chirag G. Patil

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Debraj Mukherjee, Barry D. Pressman, Deborah Krakow, David L. Rimoin and Moise Danielpour

Object

Achondroplasia may be associated with compression at the cervicomedullary junction. Determining which patients are at greatest risk for neurological complications of cervicomedullary compression can be difficult. In the current study the authors reviewed their records to determine the incidence and clinical significance of dynamic cervicomedullary stenosis and obstruction of CSF flow along with surgical outcomes following posterior fossa decompression.

Methods

The authors reviewed 34 consecutive cases involving symptomatic children with achondroplasia undergoing cervicomedullary decompression performed by a single surgeon over 11 years. Of these patients, 29 had undergone preoperative dynamic MRI of the cervicomedullary junction with cine (cinema) CSF flow studies; 13 of these patients underwent postoperative dynamic MRI studies. Clinical outcomes included changes in polysomnography, head circumference percentile, and fontanel characteristics. Radiographic outcomes included changes in dynamic spinal cord diameter, improvement in CSF flow at the foramen magnum, and change in the Evans ratio.

Results

Patients were predominantly female, with a mean age at presentation of 6.6 years and mean follow-up of 3.7 years (range 1–10 years).

All patients had moderate to excellent improvement in postoperative polysomnography, slight decrease in average head circumference percentile (from 46.9th percentile to 45.7th percentile), and no subjective worsening of fontanel characteristics. The Evans ratio decreased by 2%, spinal cord diameter increased an average of 3.1 mm, 5.2 mm, and 0.2 mm in the neutral, flexed, and extended positions, respectively, and CSF flow improved qualitatively in all 3 positions. There were no postoperative infections, CSF leaks, or other major complications. None of the patients undergoing initial foramen magnum decompression performed at our medical center required reoperation.

Conclusions

Patients with achondroplasia and symptomatic cervicomedullary compression have increased risk of dynamic stenosis at the foramen magnum evident upon dynamic cine MRI. Operative decompression may be offered with low risk of complications or need for reoperation.

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Kaisorn L. Chaichana, Debraj Mukherjee, Owoicho Adogwa, Joseph S. Cheng and Matthew J. McGirt

Object

Lumbar discectomy is the most common surgical procedure performed in the US for patients experiencing back and leg pain from herniated lumbar discs. However, not all patients will benefit from lumbar discectomy. Patients with certain psychological predispositions may be especially vulnerable to poor clinical outcomes.

The goal of this study was therefore to determine the role that preoperative depression and somatic anxiety have on long-term back and leg pain, disability, and quality of life (QOL) for patients undergoing single-level lumbar discectomy.

Methods

In 67 adults undergoing discectomy for a single-level herniated lumbar disc, the authors determined quantitative measurements of leg and back pain (visual analog scale [VAS]), quality of life (36-Item Short Form Health Survey [SF-36]), and disease-specific disability (Oswestry Disability Index) preoperatively and at 6 weeks, 3, 6, and 12 months after surgery. The degree of preoperative depression and somatization was assessed using the Zung Self-Rating Depression Scale and a modified somatic perception questionnaire (MSPQ). Multivariate regression analyses were performed to assess associations between Zung Scale and MSPQ scores with achievement of a minimum clinical important difference (MCID) in each outcome measure by 12 months postoperatively.

Results

All patients completed 12 months of follow-up. Overall, a significant improvement in VAS leg pain, VAS back pain, Oswestry Disability Index, and SF-36 Physical Component Summary scores was observed by 6 weeks after surgery. Improvements in all outcomes were maintained throughout the 12-month follow-up period. Increasing preoperative depression (measured using the Zung Scale) was associated with a decreased likelihood of achieving an MCID in disability (p = 0.006) and QOL (p = 0.04) but was not associated with VAS leg pain (p = 0.96) or back pain (p = 0.85) by 12 months. Increasing preoperative somatic anxiety (measured using the MSPQ) was associated with decreased likelihood of achieving an MCID in disability (p = 0.002) and QOL (p = 0.03) but was not associated with leg pain (p = 0.64) or back pain (p = 0.77) by 12 months.

Conclusions

The Zung Scale and MSPQ are valuable tools for stratifying risk in patients who may not experience clinically relevant improvement in disability and QOL after discectomy. Efforts to address these confounding and underlying contributors of depression and heightened somatic anxiety may improve overall outcomes after lumbar discectomy.

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Holly Dickinson, Christine Carico, Miriam Nuño, Debraj Mukherjee, Alicia Ortega, Keith L. Black and Chirag G. Patil

OBJECT

Research on readmissions has been influenced by efforts to reduce hospital cost and avoid penalties stipulated by the Centers for Medicare and Medicaid Services. Less emphasis has been placed on understanding these readmissions and their impact on patient outcomes. This study 1) delineates reasons for readmission, 2) explores factors associated with readmissions, and 3) describes their impact on the survival of glioblastoma patients.

METHODS

The authors conducted a retrospective review of 362 cases involving patients with glioblastoma undergoing biopsy or tumor resection at their institution between 2003 and 2011. Reasons for re-hospitalization were characterized according to whether or not they were related to surgery and considered preventable. Multivariate analyses were conducted to identify the effect of readmission on survival and determine factors associated with re-hospitalizations.

RESULTS

Twenty-seven (7.5%) of 362 patients experienced unplanned readmissions within 30 days of surgery. Six patients (22.2%) were readmitted by Day 7, 14 (51.9%) by Day 14, and 20 (74.1%) by Day 21. Neurological, infectious, and thromboembolic complications were leading reasons for readmission, accounting for, respectively, 37.0%, 29.6%, and 22.2% of unplanned readmissions. Twenty-one (77.8%) of the 27 readmissions were related to surgery and 19 (70.4%) were preventable. The adjusted hazard ratio of mortality associated with a readmission was 2.03 (95% CI 1.3–3.1). Higher-functioning patients (OR 0.96, 95% CI 0.9–1.0) and patients discharged home (OR 0.21, 95% CI 0.1–0.6) were less likely to get readmitted.

CONCLUSIONS

An overwhelming fraction of documented unplanned readmissions were considered preventable and related to surgery. Patients who were readmitted to the hospital within 30 days of surgery had twice the risk of mortality compared with patients who were not readmitted.

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Miriam Nuño, Christine Carico, Debraj Mukherjee, Diana Ly, Alicia Ortega, Keith L. Black and Chirag G. Patil

OBJECT

The Agency for Healthcare Research and Quality patient safety indicators (PSIs) and the Centers for Medicare and Medicaid Services hospital-acquired conditions (HACs) are administrative data-based metrics. The use of these outcomes as standard performance measures has been discussed in previous studies. With the objective of determining the applicability of these events as performance metrics among patients undergoing brain tumor surgery, this study had 2 aims: 1) to evaluate the association between PSIs, HACs, and in-hospital mortality rates; and 2) to determine a correlation between hospital volume, PSIs, and HACs.

METHODS

Patients with brain tumors treated between 1998 and 2009 were captured in the Nationwide Inpatient Sample database. Hospitals were categorized into groups according to surgical volume. Associations between PSIs, HACs, and in-hospital mortality rates were studied. Factors associated with a PSI, HAC, and mortality were evaluated in a multivariate setting.

RESULTS

A total of 444,751 patients with brain tumors underwent surgery in 1311 hospitals nationwide. Of these, 7.4% of patients experienced a PSI, 0.4% an HAC, and 1.9% died during their hospitalization. The occurrence of a PSI was strongly associated with mortality. Patients were 7.6 times more likely to die (adjusted odds ratio [aOR] 7.6, CI 6.7–8.7) with the occurrence of a PSI in a multivariate analysis. Moderate to strong associations were found between HACs, PSIs, and hospital volume. Patients treated at the highest-volume hospitals compared with the lowest-volume ones had reduced odds of a PSI (aOR 0.9, CI 0.8–1.0) and HAC (aOR 0.5, CI 0.5–0.08).

CONCLUSIONS

Patient safety-related adverse events were strongly associated with in-hospital mortality. Moderate to strong correlations were found between PSIs, HACs, and hospital procedural volume. Patients treated at the highest-volume hospitals had consistently lower rates of mortality, PSIs, and HACs compared with those treated at the lowest-volume facilities.

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Debraj Mukherjee, Kaisorn L. Chaichana, Ziya L. Gokaslan, Oran Aaronson, Joseph S. Cheng and Matthew J. McGirt

Object

Malignant primary osseous spinal neoplasms are aggressive tumors that remain associated with poor outcomes despite aggressive multidisciplinary treatment measures. To date, prognosis for patients with these tumors is based on results from small single-center patient series and controlled trials. Large population-based observational studies are lacking. To assess national trends in histology-specific survival, the authors reviewed patient survival data spanning 30 years (1973–2003) from the Surveillance, Epidemiology, and End Results (SEER) registry, a US population-based cancer registry.

Methods

The SEER registry was queried to identify cases of histologically confirmed primary spinal chordoma, chondrosarcoma, osteosarcoma, or Ewing sarcoma using coding from the International Classification of Disease for Oncology, Third Edition. Association of survival with histology, metastasis status, tumor site, and year of diagnosis was assessed using Cox proportional-hazards regression analysis.

Results

A total of 1892 patients were identified with primary osseous spinal neoplasms (414 with chordomas, 579 with chondrosarcomas, 430 with osteosarcomas, and 469 with Ewing sarcomas). Chordomas presented in older patients (60 ± 17 years; p < 0.01) whereas Ewing sarcoma presented in younger patients (19 ± 11 years; p < 0.01) compared with patients with all other tumors. The relative incidence of each tumor type remained similar per decade from 1973 to 2003. African Americans comprised a significantly greater proportion of patients with osteosarcomas than other tumors (9.6% vs 3.5%, respectively; p < 0.01). Compared with the sacrum, the mobile spine was more likely to be the site of tumor location for chordomas than for all other tumors (47% vs 23%, respectively; p < 0.05). Osteosarcoma and Ewing sarcoma were 3 times more likely than chondrosarcoma and chordoma to present with metastasis (31% vs 8%, respectively). Resection was performed more frequently for chordoma (88%) and chondrosarcoma (89%) than for osteosarcoma (61%) and Ewing sarcoma (53%). Overall median survival was histology-specific (osteosarcoma, 11 months; Ewing sarcoma, 26 months; chondrosarcoma, 37 months; chordoma, 50 months) and significantly worse in patients with metastasis at presentation for all tumor types. Survival did not significantly differ as a function of site (mobile spine vs sacrum/pelvis) for any tumor type, but more recent year of diagnosis was associated with improved survival for isolated spinal Ewing sarcoma (hazard ration [HR] 0.95; p = 0.001), chondrosarcoma (HR 0.98; p = 0.009), and chordoma (HR 0.98; p = 0.10), but not osteosarcoma.

Conclusions

In this analysis of a 30-year, US population-based cancer registry (SEER), the authors provide nationally representative prognosis and survival data for patients with malignant primary spinal osseous neoplasms. Overall patient survival has improved for isolated spine tumors with advancements in care over the past 4 decades. These results may be helpful in providing historical controls for understanding the efficacy of new treatment paradigms, patient education, and guiding level of aggressiveness in treatment strategies.

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Daniel Lubelski, Roy Xiao, Debraj Mukherjee, William W. Ashley, Timothy Witham, Henry Brem, Judy Huang and Stacey Quintero Wolfe

OBJECTIVE

Neurosurgery seeks to attract the best and brightest medical students; however, there is often a lack of early exposure to the field, among other possible barriers. The authors sought to identify successful practices that can be implemented to improve medical student recruitment to neurosurgery.

METHODS

United States neurosurgery residency program directors were surveyed to determine the number of medical student rotators and medical students matching into a neurosurgery residency from their programs between 2010 and 2016. Program directors were asked about the ways their respective institutions integrated medical students into departmental clinical and research activities.

RESULTS

Complete responses were received from 30/110 institutions. Fifty-two percent of the institutions had neurosurgery didactic lectures for 1st- and 2nd-year medical students (MS1/2), and 87% had didactics for MS3/4. Seventy-seven percent of departments had a neurosurgery interest group, which was the most common method used to integrate medical students into the department. Other forms of outreach included formal mentorship programs (53%), lecture series (57%), and neurosurgery anatomy labs (40%). Seventy-three percent of programs provided research opportunities to medical students, and 57% indicated that the schools had a formal research requirement. On average, 3 medical students did a rotation in each neurosurgery department and 1 matched into neurosurgery each year. However, there was substantial variability among programs. Over the 2010–2016 period, the responding institutions matched as many as 4% of the graduating class into neurosurgery per year, whereas others matched 0%–1%. Departments that matched a greater (≥ 1% per year) number of medical students into neurosurgery were significantly more likely to have a neurosurgery interest group and formal research requirements. A greater percentage of high-matching programs had neurosurgery mentorship programs, lecture series, and cadaver training opportunities compared to the other institutions.

CONCLUSIONS

In recent decades, the number of applicants to neurosurgery has decreased. A major deterrent may be the delayed exposure of medical students to neurosurgery. Institutions with early preclinical exposure, active neurosurgery interest groups, research opportunities, and strong mentorship recruit and match more students into neurosurgery. Implementing such initiatives on a national level may increase the number of highly qualified medical students pursuing neurosurgery.

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Georgios A. Zenonos, Juan C. Fernandez-Miranda, Debraj Mukherjee, Yue-Fang Chang, Klea Panayidou, Carl H. Snyderman, Eric W. Wang, Raja R. Seethala and Paul A. Gardner

OBJECTIVE

There are currently no reliable means to predict the wide variability in behavior of clival chordoma so as to guide clinical decision-making and patient education. Furthermore, there is no method of predicting a tumor’s response to radiation therapy.

METHODS

A molecular prognostication panel, consisting of fluorescence in situ hybridization (FISH) of the chromosomal loci 1p36 and 9p21, as well as immunohistochemistry for Ki-67, was prospectively evaluated in 105 clival chordoma samples from November 2007 to April 2016. The results were correlated with overall progression-free survival after surgery (PFSS), as well as progression-free survival after radiotherapy (PFSR).

RESULTS

Although Ki-67 and the percentages of tumor cells with 1q25 hyperploidy, 1p36 deletions, and homozygous 9p21 deletions were all found to be predictive of PFSS and PFSR in univariate analyses, only 1p36 deletions and homozygous 9p21 deletions were shown to be independently predictive in a multivariate analysis. Using a prognostication calculator formulated by a separate multivariate Cox model, two 1p36 deletion strata (0%–15% and > 15% deleted tumor cells) and three 9p21 homozygous deletion strata (0%–3%, 4%–24%, and ≥ 25% deleted tumor cells) accounted for a range of cumulative hazard ratios of 1 to 56.1 for PFSS and 1 to 75.6 for PFSR.

CONCLUSIONS

Homozygous 9p21 deletions and 1p36 deletions are independent prognostic factors in clival chordoma and can account for a wide spectrum of overall PFSS and PFSR. This panel can be used to guide management after resection of clival chordomas.

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Chirag G. Patil, Anthony Yi, Adam Elramsisy, Jethro Hu, Debraj Mukherjee, Dwain K. Irvin, John S. Yu, Serguei I. Bannykh, Keith L. Black and Miriam Nuño

Object

The prognosis of patients with glioblastoma who present with multifocal disease is not well documented. The objective of this study was to determine whether multifocal disease on initial presentation is associated with worse survival.

Methods

The authors retrospectively reviewed records of 368 patients with newly diagnosed glioblastoma and identified 47 patients with multifocal tumors. Each patient with a multifocal tumor was then matched with a patient with a solitary glioblastoma on the basis of age, Karnofsky Performance Scale (KPS) score, and extent of resection, using a propensity score matching methodology. Radiation and temozolomide treatments were also well matched between the 2 cohorts. Kaplan-Meier estimates and log-rank tests were used to compare patient survival.

Results

The incidence of multifocal tumors was 12.8% (47/368). The median age of patients with multifocal tumors was 61 years, 76.6% had KPS scores ≥ 70, and 87.2% underwent either a biopsy or partial resection of their tumors. The 47 patients with multifocal tumors were almost perfectly matched on the basis of age (p = 0.97), extent of resection (p = 1.0), and KPS score (p = 0.80) compared with 47 patients with a solitary glioblastoma. Age (>65 years), partial resection or biopsy, and low KPS score (<70) were associated with worse median survival within the multifocal group. In the multifocal group, 19 patients experienced tumor progression on postradiation therapy MRI, compared with 11 patients (26.8%) with tumor progression in the unifocal group (p = 0.08). Patients with multifocal tumors experienced a significantly shorter median overall survival of 6 months (95% CI 4–10 months), compared with the 11-month median survival (95% CI 10–19 months) of the matched solitary glioblastoma group (p = 0.02, log-rank test). Two-year survival rates were 4.3% for patients with multifocal tumors and 29.0% for the unifocal cohort. Patients with newly diagnosed multifocal tumors were found to have an almost 2-fold increase in the hazard of death compared with patients with solitary glioblastoma (hazard ratio 1.8, 95% CI 1.1–3.1; p = 0.02). Tumor samples were analyzed for expression of phosphorylated mitogen-activated protein kinase, phosphatase and tensin homolog, O6-methylguanine-DNA methyltransferase, laminin β1 and β2, as well as epidermal growth factor receptor amplification, and no significant differences in expression profile between the multifocal and solitary glioblastoma groups was found.

Conclusions

Patients with newly diagnosed multifocal glioblastoma on presentation experience significantly worse survival than patients with solitary glioblastoma. Patients with multifocal tumors continue to pose a therapeutic challenge in the temozolomide era and magnify the challenges faced while treating patients with malignant gliomas.