Single-cell analysis reveals diversity of tumor-associated macrophages and their interactions with T lymphocytes in glioblastoma.

Glioblastoma (GBM) is an aggressive primary CNS malignancy and clinical outcomes have remained stagnant despite introduction of new treatments. Understanding the tumor microenvironment (TME) in which tumor associated macrophages (TAMs) interact with T cells has been of great interest. Although previous studies examining TAMs in GBM have shown that certain TAMs are associated with specific clinical and/or pathologic features, these studies used an outdated M1/M2 paradigm of macrophage polarization and failed to include the continuum of TAM states in GBM. Perhaps most significantly, the interactions of TAMs with T cells have yet to be fully explored. Our study uses single-cell RNA sequencing data from adult IDH-wildtype GBM, with the primary aim of deciphering the cellular interactions of the 7 TAM subtypes with T cells in the GBM TME. Furthermore, the interactions discovered herein are compared to IDH-mutant astrocytoma, allowing for focus on the cellular ecosystem unique to GBM. The resulting ligand-receptor interactions, signaling sources, and global communication patterns discovered provide a framework for future studies to explore methods of leveraging the immune system for treating GBM.

A New Finding on Magnetic Resonance Imaging for Diagnosis of Hemifacial Spasm with High Accuracy and Interobserver Correlation.

Among patients with clinical hemifacial spasm (HFS), imaging exams aim to identify the neurovascular conflict (NVC) location. It has been proven that the identification in the preoperative exam increases the rate of surgical success. Despite the description of specific magnetic resonance image (MRI) acquisitions, the site of neurovascular compression is not always visualized. The authors describe a new MRI finding that helps in the diagnosis of HFS, and evaluate the sensitivity, specificity, and interobserver correlation of the described sign. A cross-sectional study including cases of hemifacial spasm treated surgically from 1 August 2011 to 31 July 2021 was performed. The MRIs of the cases were independently evaluated by two experienced neuroradiologists, who were blinded regarding the side of the symptom. The neuroradiologists were assigned to evaluate the MRIs in two separate moments. Primarily, they evaluated whether there was a neurovascular conflict based on the standard technique. Following this initial analysis, the neuroradiologists received a file with the description of the novel sign, named Prevedello Sign (PS). In a second moment, the same neuroradiologists were asked to identify the presence of the PS and, if it was present, to report on which side. A total of 35 patients were included, mostly females (65.7%) with a mean age of 59.02 (+0.48). Since the 35 cases were independently evaluated by two neuroradiologists, a total of 70 reports were included in the analysis. The PS was present in 66 patients (sensitivity of 94.2%, specificity of 91.4% and positive predictive value of 90.9%). When both analyses were performed in parallel (standard plus PS), the sensitivity increased to 99.2%. Based on the findings of this study, the authors conclude that PS is helpful in determining the neurovascular conflict location in patients with HFS. Its presence, combined with the standard evaluation, increases the sensitivity of the MRI to over 99%, without increasing risks of harm to patients or resulting in additional costs.

A silent corticotroph adenoma: making the case for a pars intermedia origin. Illustrative case.

BACKGROUND: Silent corticotroph adenomas (SCAs) are the only pituitary adenomas thought to originate from the pars intermedia. This case report presents the rare finding of a multimicrocystic corticotroph macroadenoma displacing the anterior and posterior lobes of the pituitary gland on magnetic resonance imaging (MRI). This finding supports the hypothesis that silent corticotroph adenomas may originate from the pars intermedia and should be considered in the differential for tumors arising from this location. OBSERVATIONS: A 55-year-old man presented with an episode of confusion and blurred vision. MRI demonstrated separation of the anterior and posterior glands by a solid-cystic lesion located within the pars intermedia that superiorly displaced the optic chiasm. Endocrinologic evaluation was unremarkable. The differential diagnosis included pituitary adenoma, Rathke cleft cyst, and craniopharyngioma. The tumor was confirmed to be an SCA on pathology and was completely removed through the endoscopic endonasal transsphenoidal approach. LESSONS: The case highlights the importance of preoperative screening for subclinical hypercortisolism for tumors arising from this location. Knowledge of a patient's preoperative functional status is critical and dictates their postoperative biochemical assessment to determine remission. The case also illustrates surgical strategies for resecting pars intermedia lesions without injuring the gland.

Spontaneous rhinorrhea: a possible concealing initial symptom of ecchordosis physaliphora. Illustrative case.

BACKGROUND: Spontaneous rhinorrhea may be the initial manifestation of ecchordosis physaliphora (EP). There are currently 47 published cases of symptomatic EP, with spontaneous rhinorrhea being one of the most prevalent symptoms. The authors report 1 case as a cause of cerebrospinal fluid (CSF) fistula. OBSERVATIONS: A 46-year-old woman presented to the authors' clinic with meningitis secondary to nasal CSF leakage. The computed tomography (CT) scan indicated an imperceptibly thin/dehiscent focus along the posterior wall of the sphenoid air cell's midline. A tumor was identified during endoscopic endonasal CSF repair surgery. EP was diagnosed in the frozen and final pathology. LESSONS: EP should be considered as a potential cause of spontaneous rhinorrhea. This initial clinical manifestation accounts for 35% of symptomatic EP cases. The prepontine and posterior sphenoid sinus wall appear to be the locations with the highest susceptibility. Surgical therapy of the fistula without excision of the lesion may result in insufficient issue resolution and recurrence.

Side-Firing Intraoperative Ultrasonograhy for Resection of Giant Pituitary Adenomas.

BACKGROUND: Suprasellar extension, cavernous sinus invasion, and involvement of intracranial vascular structures and cranial nerves are among the challenges faced by surgeons operating on giant pituitary macroadenomas. Intraoperative tissue shifts may render neuronavigation techniques inaccurate. Intraoperative magnetic resonance imaging can solve this problem, but it may be costly and time consuming. However, intraoperative ultrasonography (IOUS) allows for quick, real-time feedback and may be particularly useful when facing giant invasive adenomas. Here, we present the first study examining technique for IOUS-guided resection specifically focusing on giant pituitary adenomas. OBJECTIVE: To describe the use of a side-firing ultrasound probe in the resection of giant pituitary macroadenomas. METHODS: We describe an operative technique using a side-firing ultrasound probe (Fujifilm/Hitachi) to identify the diaphragma sellae, confirm optic chiasm decompression, identify vascular structures related to tumor invasion, and maximize extent of resection in giant pituitary macroadenomas. RESULTS: Side-firing IOUS allows for identification of the diaphragma sellae to help prevent intraoperative cerebrospinal fluid leak and maximize extent of resection. Side-firing IOUS also aids in confirmation of decompression of the optic chiasm via identification of a patent chiasmatic cistern. Furthermore, direct identification of the cavernous and supraclinoid internal carotid arteries and arterial branches is achieved when resecting tumors with significant parasellar and suprasellar extension. CONCLUSIONS: We describe an operative technique in which side-firing IOUS may assist in maximizing extent of resection and protecting vital structures during surgery for giant pituitary adenomas. Use of this technology may be particularly valuable in settings in which intraoperative magnetic resonance imaging is not available.

Reducing ICU Length of Stay: The Impact of a Multidisciplinary Perioperative Pathway in Vestibular Schwannoma.

Objective This study was aimed to evaluate the impact of a multidisciplinary perioperative pathway on length of stay (LOS) and postoperative outcomes after vestibular schwannoma surgery. Setting This study was conducted in a tertiary skull base center. Main Outcome Measures The impact of the pathway on intensive care unit (ICU) LOS was evaluated as the primary outcome measure of the study. Overall resource LOS, postoperative complications, and readmission rates were also evaluated as secondary outcome measures. Methods Present study is a retrospective review. Results A universally adopted perioperative pathway was developed to include standardization of preoperative education and expectations, intraoperative anesthetic delivery, postoperative nursing education, postoperative rehabilitation, and utilization of stepdown and surgical floor units after ICU stay. Outcomes were measured for 95 consecutive adult patients who underwent surgical resection for vestibular schwannoma (40 cases before implementation of the perioperative pathway and 55 cases after implementation). There were no significant differences in the two groups with regard to tumor size, operative time, or medical comorbidities. The mean ICU LOS decreased from 2.1 in the preimplementation group to 1.6 days in the postimplementation group ( p = 0.02). There were no significant differences in overall resource LOS postoperative complications or readmission rates between groups. Conclusion Multidisciplinary, perioperative neurotologic pathways can be effective in lowering ICU LOS in patients undergoing vestibular schwannoma surgery without compromising quality of care. Further research is needed to continue to sustain and continuously improve these and other measures, while continuing to provide high-quality care to this patient population.

Complications in Endoscopic Pituitary Surgery.

Pituitary surgery has undergone rapid advancements in the last 30 years, secondary to improved surgical techniques and technologies, including those that allow endoscopic approaches. Although the endoscopic endonasal approach (EEA) offers minimally invasive access to the region of the pituitary gland, complications are a significant consideration for the combined otolaryngology-neurosurgery team that is preparing for a case. In this article, we discuss various complications related to the EEA in pituitary surgery and explore ways to plan for and avoid them during surgery.

Long-term tumor control after endoscopic endonasal resection of craniopharyngiomas: comparison of gross-total resection versus subtotal resection with radiation therapy.

OBJECTIVE: Surgical management of craniopharyngiomas (CPAs) is challenging. Controversy exists regarding the optimal goals of surgery. The purpose of this study was to compare the long-term outcomes of patients who underwent gross-total resection with the outcomes of those who underwent subtotal resection of their CPA via an endoscopic endonasal approach. METHODS: From a prospectively maintained database of all endoscopic endonasal approaches performed at Weill Cornell Medicine, only patients with CPAs with > 3 years of follow-up after surgery were included. The primary endpoint was radiographic progression. Data were collected on baseline demographics, imaging, endocrine function, visual function, and extent of resection. RESULTS: A total of 44 patients with a mean follow-up of 5.7 ± 2.6 years were included. Of these patients, 14 (31.8%) had prior surgery. GTR was achieved in 77.3% (34/44) of all patients and 89.5% (34/38) of patients in whom it was the goal of surgery. Preoperative tumor volume < 10 cm3 was highly predictive of GTR (p < 0.001). Radiation therapy was administered within the first 3 months after surgery in 1 (2.9%) of 34 patients with GTR and 7 (70%) of 10 patients with STR (p < 0.001). The 5-year recurrence-free/progression-free survival rate was 75.0% after GTR and 25.0% after STR (45% in subgroup with STR plus radiotherapy; p < 0.001). The time to recurrence after GTR was 30.2 months versus 13 months after STR (5.8 months in subgroup with STR plus radiotherapy; p < 0.001). Patients with GTR had a lower rate of visual deterioration and higher rate of return to work or school compared with those with STR (p = 0.02). Patients with GTR compared to STR had a lower rate of CSF leakage (0.0% vs 30%, p = 0.001) but a higher rate of diabetes insipidus (85.3% vs 50%, p = 0.02). CONCLUSIONS: GTR, which is possible to achieve in smaller tumors, resulted in improved tumor control, better visual outcome, and better functional recovery but a higher rate of diabetes insipidus compared with STR, even when the latter was supplemented with postoperative radiation therapy. GTR should be the goal of craniopharyngioma surgery, when achievable with minimal morbidity.

Defining the relative utility of lumbar spine surgery: A systematic literature review of common surgical procedures and their impact on health states.

Degenerative lumbar spondylosis is a common indication for patients undergoing spine surgery. As healthcare costs rise, measuring quality of life (QOL) gains after surgical procedures is critical in assessing value. We set out to: 1) compare baseline and postoperative EuroQol-5D (EQ-5D) scores for lumbar spine surgery and common surgical procedures to obtain post-operative quality-adjusted life year (QALY) gain, and 2) establish the relative utility of lumbar spine surgery as compared to other commonly performed surgical procedures. A systematic literature review was conducted to identify all studies reporting preoperative/baseline and postoperative EQ-5D scores for common surgical procedures. For each study, the number of patients included and baseline/preoperative and follow-up mean EQ-5D scores were recorded, and mean QALY gained for each intervention was calculated. A total of 67 studies comprising 95,014 patients were identified. Patients with lumbar spondylosis had the worst reported QOL at baseline compared to other surgical cohorts. The greatest QALY gain was seen in patients undergoing hip arthroplasty (0.38), knee arthroplasty (0.35) and lumbar spine surgery (0.32), nearly 2.5-fold greater QALY gained than for all other procedures. The low preoperative QOL, coupled with the improvements offered with surgery, highlight the utility and value of lumbar spine surgery compared to other common surgical procedures.

Bone Cement Cranioplasty Reduces Cerebrospinal Fluid Leak Rate after Microvascular Decompression: A Single-Institutional Experience.

Background Microvascular decompression (MVD) is a common surgical treatment for cranial nerve compression, though cerebrospinal fluid (CSF) leak is a known complication of this procedure. Bone cement cranioplasty may reduce rates of CSF leak. Objective To compare rates of CSF leak before and after implementation of bone cement cranioplasty for the reconstruction of cranial defects after MVD. Methods Retrospective chart review was performed of patients who underwent MVD through retrosigmoid craniectomy for cranial nerve compression at a single institution from 1998 to 2017. Study variables included patient demographics, medical history, type of closure, and postoperative complications such as CSF leak, meningitis, lumbar drain placement, and ventriculoperitoneal shunt insertion. Cement and noncement closure groups were compared, and predictors of CSF leak were assessed using a multivariate logistic regression model. Results A total of 547 patients treated by 10 neurosurgeons were followed up for more than 20 years, of whom 288 (52.7%) received cement cranioplasty and 259 (47.3%) did not. Baseline comorbidities were not significantly different between groups. CSF leak rate was significantly lower in the cement group than in the noncement group (4.5 vs. 14.3%; p < 0.001). This was associated with significantly fewer patients developing postoperative meningitis (0.7 vs. 5.2%; p = 0.003). Multiple logistic regression model demonstrated noncement closure as the only independent predictor of CSF leak (odds ratio: 3.55; 95% CI: 1.78-7.06; p < 0.001). Conclusion CSF leak is a well-known complication after MVD. Bone cement cranioplasty significantly reduces the incidence of postoperative CSF leak and other complications. Modifiable risk factors such as body mass index were not associated with the development of CSF leak.

Endonasal Endoscopic Fenestration of Rathke's Cleft Cysts: Whether to Leave the Fenestration Open or Closed?

Introduction Rathke's cleft cysts (RCC) are generally treated with transsphenoidal fenestration and cyst drainage. If no cerebrospinal fluid (CSF) leak is created, the fenestration can be left open. If CSF is encountered, a watertight closure must be created to prevent postoperative CSF leak, though sellar closure has theoretically been linked with higher recurrence rate. In this study, we investigate the relationship between sellar closure, rate of postoperative CSF leak, and RCC recurrence. Methods Retrospective review of a prospective database of all endoscopic endonasal RCC fenestrations and cases were divided based on closure. The "open" group included patients who underwent fenestration of the RCC, whereas the "closed" group included patients whose RCC was treated with fat and a rigid buttress ± a nasoseptal flap. The rate of intra- and postoperative CSF leak and radiographic recurrence was determined. Results The closed group had a higher rate of suprasellar extension (odds ratio [OR]: 8.0, p = 0.032) and intraoperative CSF leak ( p ≤ 0.001). There were 54.8% intraoperative CSF leaks and no postoperative CSF leaks. Radiologic recurrence rate for the closed group (35.0%) was three times higher than the open group (9.1%; risk ratio [RR] = 3.85, p = 0.203), but not powered to show significance. None of the radiologic recurrences required reoperation. Conclusion Maintaining a patent fenestration between an RCC and the sphenoid sinus is important in reducing the rate of radiographic recurrence. Closure of the fenestration may be required to prevent CSF leak. While closure increases the rate of radiographic recurrence, reoperation for recurrent RCC is still an uncommon event.

Long-term outcomes after endoscopic endonasal surgery for nonfunctioning pituitary macroadenomas.

OBJECTIVE: Nonfunctioning pituitary adenomas are benign, slow-growing tumors. After gross-total resection (GTR) or subtotal resection (STR), tumors can recur or progress and may ultimately require additional intervention. A greater understanding of long-term recurrence and progression rates following complete or partial resection and the need for further intervention will help clinicians provide meaningful counsel for their patients and assist data-driven decision-making. METHODS: The authors retrospectively analyzed their institutional database for patients undergoing endoscopic endonasal surgery (EES) for nonfunctioning pituitary macroadenomas (2003-2014). Only patients with follow-up of at least 5 years after surgery were included. Tumor volumes were measured on pre- and postoperative MRI. Tumor recurrence was defined as the presence of a 0.1-cm3 tumor volume after GTR, and tumor progression was defined as a 25.0% increase in residual tumor after STR. RESULTS: A total of 190 patients were included, with a mean age of 63.8 ± 13.2 years; 79 (41.6%) were female. The mean follow-up was 75.0 ± 18.0 months. GTR was achieved in 127 (66.8%) patients. In multivariate analysis, age (p = 0.04), preoperative tumor volume (p = 0.03), Knosp score (p < 0.001), and Ki-67 (p = 0.03) were significant predictors of STR. In patients with GTR, the probability of recurrence at 5 and 10 years was 3.9% and 4.7%, and the probability of requiring treatment for recurrence was 0.79% and 1.6%, respectively. In 63 patients who underwent STR, 6 (9.5%) received early postoperative radiation and did not experience progression, while the remaining 57 (90.5%) were observed. Of these, the probability of disease progression at 5 and 10 years was 21% and 24.5%, respectively, and the probability of requiring additional treatment for progression was 17.5% and 21%. Predictors of recurrence or progression in the entire group were Knosp score (p < 0.001) and elevated Ki-67 (p = 0.03). Significant predictors of progression after STR in those who did not receive early radiotherapy were cavernous sinus location (p < 0.05) and tumor size > 1.0 cm3 (p = 0.005). CONCLUSIONS: Following GTR for nonfunctioning pituitary adenomas, the 10-year chance of recurrence is low and the need for treatment even lower. After STR, although upfront radiation therapy may prevent progression, even without radiotherapy, the need for intervention at 10 years is only approximately 20% and a period of observation may be warranted to prevent unnecessary prophylactic radiation therapy. Tumor volume > 1 cm3, Knosp score ≥ 3, and Ki-67 ≥ 3% may be useful metrics to prompt closer follow-up or justify early prophylactic radiation therapy.

Endoscopic Endonasal Transclival Resection of a Pontine Metastasis: Case Report and Operative Video.

BACKGROUND AND IMPORTANCE: Brainstem lesions are challenging to manage, and surgical options have been controversial. Stereotactic radiosurgery (SRS) has been used for local control, but life-threatening toxicities from 0% to 9.5% have been reported. Several microsurgical approaches involving safe entry zones have been developed to optimize the exposure and minimize complications in different portions of the brainstem, but require extensive drilling and manipulation of neurovascular structures. With recent advancements, the endoscopic endonasal approach (EEA) can provide direct visualization of ventral brainstem. No case has been reported of EEA to remove a brainstem metastasis. CLINICAL PRESENTATION: We present an illustrative case of a 68-yr-old female with metastatic colon cancer who presented with 2.8 × 2.7 × 2.1 cm (7.9 cm3) heterogeneously enhancing, right ventral pontine lesion with extensive edema. She underwent endoscopic endonasal transclival approach, and gross total resection of the lesion was achieved. CONCLUSION: The endoscopic approach may offer certain advantages for removal of ventral brainstem lesions, as it can provide direct visualization of important neurovascular structures, especially, if the lesion displaces the tracts and comes superficial to the pial surface.

Endoscopic transorbital approach to the infratemporal fossa and parapharyngeal space: a cadaveric study.

OBJECTIVE: The infratemporal fossa (ITF) and parapharyngeal space are anatomical regions that can be challenging to access without the use of complex, cosmetically disfiguring approaches. With advances in endoscopic techniques, a new group of surgical approaches to access the intracranial space through the orbit has been recently referred to as transorbital neuroendoscopic surgery (TONES). The objective of this study was to establish a transorbital endoscopic approach utilizing the inferior orbital fissure (IOF) to gain access to the ITF and parapharyngeal space and provide a detailed endoscopic anatomical description of this approach. METHODS: Four cadaveric heads (8 sides) were dissected using a TONES approach through the IOF to reach the ITF and parapharyngeal space, providing stepwise dissection with detailed anatomical findings and a description of each step. RESULTS: An inferior eyelid approach was made with subperiosteal periorbital dissection to the IOF. The zygomatic and greater wing of the sphenoid were drilled, forming the boundaries of the IOF. The upper head of the lateral pterygoid muscle in the ITF and parapharyngeal space was removed, and 7 distinct planes were described, each with its own anatomical contents. The second part of the maxillary artery was mainly found in plane 1 between the temporalis laterally and the lateral pterygoid muscle in plane 2. The branches of the mandibular nerve (V3) and middle meningeal artery (MMA) were identified in plane 3. Plane 4 was formed by the fascia of the medial pterygoid muscle (MTM) and the tensor veli palatini muscle. The prestyloid segment, found in plane 5, was composed mainly of fat and lymph nodes. The parapharyngeal carotid artery in the poststyloid segment, found in plane 7, was identified after laterally dissecting the styloid diaphragm, found in plane 6. V3 and the origin of the levator and tensor veli palatini muscles serve as landmarks for identification of the parapharyngeal carotid artery. CONCLUSIONS: The transorbital endoscopic approach provides excellent access to the ITF and parapharyngeal space compared to previously described complex and morbid transfacial or transcranial approaches. Using the IOF is an important and useful landmark that permits a wide exposure.

Incidence and risk factors associated with reoperation for sellar hematoma following endoscopic transsphenoidal pituitary surgery.

OBJECTIVE: Postoperative sellar hematoma is an uncommon complication of endonasal endoscopic transsphenoidal surgery (EETS) for pituitary adenoma that often requires emergency surgical evacuation. Sellar hematomas can cause mass effect and compress parasellar structures, leading to clinically significant symptoms such as visual impairment and severe headache. The objective of this study was to determine the incidence and risk factors associated with reoperation for postoperative hematoma after EETS for pituitary adenoma. METHODS: The authors reviewed a prospectively acquired database of EETS for pituitary adenoma over 13 years at Weill Cornell Medicine, NewYork-Presbyterian Hospital and identified cases that required reoperation for confirmed hematoma. They also reviewed clinical and radiographic data of a consecutive series of patients undergoing EETS for pituitary adenoma who did not have postoperative hematoma, which served as the control group. Demographic data and risk factors were compared between the groups using univariate and multivariate analyses via binary logistic regression. RESULTS: Among a cohort of 583 patients undergoing EETS for pituitary adenoma, 9 patients (1.5%) required operation for sellar hematoma evacuation. All 9 patients with reoperation for sellar hematoma presented with worsening in their vision, and severe headache was present in 67%. New postoperative endocrine dysfunction developed in 78%. Clot evacuation improved vision in 88%. The mean time to hematoma evacuation was 4.5 days. The median length of stay for patients with sellar hematoma was 8 days (range 4-210 days) compared with a median length of stay of 3 days (range 1-32 days) for the control patients (p < 0.005). Significant risk factors in univariate analysis were tumor diameter ≥ 30 mm (p < 0.005), suprasellar extension (p < 0.005), tumor volume (p < 0.005), cavernous sinus invasion (p < 0.05), gonadotroph histology (p < 0.05), antiplatelet use (p < 0.05), and elevated BMI (p < 0.05). On multivariate analysis, tumor diameter ≥ 30 mm (OR 4.555, CI 1.30-28.90; p < 0.05) and suprasellar extension (OR 1.048, CI 1.01-1.10; p < 0.05) were found to be the only independent predictors of sellar hematoma. The incidence of hematoma in tumors ≥ 30 mm was 5% (7/139). CONCLUSIONS: Postoperative sellar hematoma requiring reoperation is a rare phenomenon after transsphenoidal surgery, often presenting with visual loss and headache. Clot evacuation results in improvement in vision, but long-term endocrinopathy often ensues. Tumor diameter ≥ 30 mm and suprasellar extent are the most reliable risk factors. Close postoperative scrutiny should be given to patients at high risk.

Genomic profile of a primary squamous cell carcinoma arising from malignant transformation of a pineal epidermoid cyst.

Malignant transformation of intracranial epidermoid cysts is a rare occurrence. We present the second case of such an event occurring in the pineal region and the first case sent for detailed genomic profiling. MRI demonstrated two lesions: a cyst in a quadrigeminal cistern with restricted diffusion on DWI-weighted images and an adjacent, peripherally enhancing tumor with cerebellar infiltration. Both the lesions were completely resected with a small residual of the epidermoid cyst. The final pathology of both lesions was consistent with epidermoid cyst and squamous cell carcinoma (SCC), respectively. The tumor specimen was sent for comprehensive genomic profiling which revealed stable microsatellite status and loss of CDKN2A/B, MTAP (exons 2-8), and PTEN (exons 6-9). Although reports of primary SCC originating from the epidermoid cyst have been previously described, this is the first description of the genomic profile of such a tumor.

Anterior cervical discectomy and fusion in the outpatient ambulatory surgery setting compared with the inpatient hospital setting: analysis of 1000 consecutive cases.

OBJECTIVE In an era of escalating health care costs and pressure to improve efficiency and cost of care, ambulatory surgery centers (ASCs) have emerged as lower-cost options for many surgical therapies. Anterior cervical discectomy and fusion (ACDF) is one of the most prevalent spine surgeries performed, and the frequency of its performance is rapidly increasing as the aging population grows. Although ASCs offer significant cost advantages over hospital-based surgical centers, concern over the safety of outpatient ACDF has slowed its adoption. The authors intended to 1) determine the safety of the first 1000 consecutive ACDF surgeries performed in their outpatient ASC, and 2) compare the safety of these outpatient ACDFs with that of consecutive ACDFs performed during the same time period in the hospital setting. METHODS A total of 1000 consecutive patients who underwent ACDF in an ACS (outpatient ACDF) and 484 consecutive patients who underwent ACDF at Vanderbilt University Hospital (inpatient ACDF) from 2006 to 2013 were included in this retrospective study of patients' medical records. Data were collected on patient demographics, comorbidities, operative details, and perioperative and 90-day morbidity. Perioperative morbidity and hospital readmission were compared between the outpatient and inpatient ACDF groups. RESULTS Of the first 1000 outpatient ACDF cases performed in the authors' ASC, 629 (62.9%) were 1-level and 365 (36.5%) were 2-level ACDFs. Mean patient age was 49.5 ± 8.6, and 484 (48.4%) were males. All patients were observed postoperatively at the ASC postanesthesia care unit (PACU) for 4 hours before being discharged home. Eight patients (0.8%) were transferred from the surgery center to the hospital postoperatively (for pain control [n = 3], chest pain and electrocardiogram changes [n = 2], intraoperative CSF leak [n = 1], postoperative hematoma [n = 1], and profound postoperative weakness and surgical reexploration [n = 1]). No perioperative deaths occurred. The 30-day hospital readmission rate was 2.2%. All 90-day surgical morbidity was similar between outpatient and inpatient cohorts for both 1-level and 2-level ACDFs. CONCLUSIONS An analysis of 1000 consecutive patients who underwent ACDF in an outpatient setting demonstrates that surgical complications occur at a low rate (1%) and can be appropriately diagnosed and managed in a 4-hour ASC PACU window. Comparison with an inpatient ACDF surgery cohort demonstrated similar results, highlighting that ACDF can be safely performed in the outpatient ambulatory surgery setting without compromising surgical safety. In an effort to decrease costs of care, surgeons can safely perform 1- and 2-level ACDFs in an ASC environment.

High Content Imaging of Early Morphological Signatures Predicts Long Term Mineralization Capacity of Human Mesenchymal Stem Cells upon Osteogenic Induction.

Human bone marrow-derived multipotent mesenchymal stromal cells, often referred to as mesenchymal stem cells (MSCs), represent an attractive cell source for many regenerative medicine applications due to their potential for multi-lineage differentiation, immunomodulation, and paracrine factor secretion. A major complication for current MSC-based therapies is the lack of well-defined characterization methods that can robustly predict how they will perform in a particular in vitro or in vivo setting. Significant advances have been made with identifying molecular markers of MSC quality and potency using multivariate genomic and proteomic approaches, and more recently with advanced techniques incorporating high content imaging to assess high-dimensional single cell morphological data. We sought to expand upon current methods of high dimensional morphological analysis by investigating whether short term cell and nuclear morphological profiles of MSCs from multiple donors (at multiple passages) correlated with long term mineralization upon osteogenic induction. Using the combined power of automated high content imaging followed by automated image analysis, we demonstrated that MSC morphology after 3 days was highly correlated with 35 day mineralization and comparable to other methods of MSC osteogenesis assessment (such as alkaline phosphatase activity). We then expanded on this initial morphological characterization and identified morphological features that were highly predictive of mineralization capacities (>90% accuracy) of MSCs from additional donors and different manufacturing techniques using linear discriminant analysis. Together, this work thoroughly demonstrates the predictive power of MSC morphology for mineralization capacity and motivates further studies into MSC morphology as a predictive marker for additional in vitro and in vivo responses.