Sellar Reconstruction With a Bioabsorbable Plate After Endoscopic Transsphenoidal Pituitary Adenoma Resection: Safe and Efficacious.

OBJECTIVE: To report outcomes of a large cohort of patients who underwent endoscopic endonasal transsphenoidal surgery (EETS) for resection of a pituitary adenoma with subsequent Resorb-X plate (RXP) sellar reconstruction. METHODS: A retrospective review of 620 EETS operations performed at a single academic center between 2005 and 2020 was conducted. RESULTS: A total of 215 EETS operations of 208 patients were identified between 2012 and 2020 who underwent reconstruction with the RXP after EETS for pituitary tumor resection with a final pathologic diagnosis of pituitary adenoma. Analysis of pooled data revealed a mean preoperative tumor volume of 6.8 cm3 (range: 0.038-51.03 cm3). Postoperative cerebrospinal fluid leak occurred in 2 patients (0.93%). Postoperative meningitis occurred in 1 patient (0.47%). There were no cases of RXP extrusion. CONCLUSIONS: The rate of postoperative CSF leak and meningitis after use of the RXP for sellar reconstruction compares favorably to other methods, including use of autologous grafts and flaps. Use of RXP during EETS is a safe and efficacious method of sellar reconstruction and may obviate the need for autologous tissue reconstruction after pituitary adenoma resection.

Epigenetic reprogramming shapes the cellular landscape of schwannoma.

Mechanisms specifying cancer cell states and response to therapy are incompletely understood. Here we show epigenetic reprogramming shapes the cellular landscape of schwannomas, the most common tumors of the peripheral nervous system. We find schwannomas are comprised of 2 molecular groups that are distinguished by activation of neural crest or nerve injury pathways that specify tumor cell states and the architecture of the tumor immune microenvironment. Moreover, we find radiotherapy is sufficient for interconversion of neural crest schwannomas to immune-enriched schwannomas through epigenetic and metabolic reprogramming. To define mechanisms underlying schwannoma groups, we develop a technique for simultaneous interrogation of chromatin accessibility and gene expression coupled with genetic and therapeutic perturbations in single-nuclei. Our results elucidate a framework for understanding epigenetic drivers of tumor evolution and establish a paradigm of epigenetic and metabolic reprograming of cancer cells that shapes the immune microenvironment in response to radiotherapy.

Surgical outcomes and risk factors for recurrence of myxopapillary ependymoma: a single-center experience.

OBJECTIVE: Myxopapillary ependymomas (MPEs) are low-grade, well-circumscribed tumors that often involve the conus medullaris, cauda equina, or filum terminale. They account for up to 5% of all tumors of the spine and 13% of spinal ependymomas, with a peak incidence between 30 and 50 years of age. Because of the rarity of MPEs, their clinical course and optimal management strategy are not well defined, and long-term outcomes remain difficult to predict. The objective of this study was to review long-term clinical outcomes of spinal MPEs and identify factors that may predict tumor resectability and recurrence. METHODS: Pathologically confirmed cases of MPE at the authors' institution were identified and medical records were reviewed. Demographics, clinical presentation, imaging characteristics, surgical technique, follow-up, and outcome data were noted. Two groups of patients-those who underwent gross-total resection (GTR) and those who underwent subtotal resection (STR)-were compared using the Mann-Whitney U-test for continuous and ordinal variables and the Fisher exact test for categorical variables. Differences were considered statistically significant at p ≤ 0.05. RESULTS: Twenty-eight patients were identified, with a median age of 43 years at the index surgery. The median postoperative follow-up duration was 107 months (range 5-372 months). All patients presented with pain. Other common presenting symptoms were weakness (25.0%), sphincter disturbance (21.4%), and numbness (14.3%). GTR was achieved in 19 patients (68%) and STR in 9 (32%). Preoperative weakness and involvement of the sacral spinal canal were more common in the STR group. Tumors were larger and spanned more spinal levels in the STR group compared with the GTR cohort. Postoperative modified McCormick Scale grades were significantly higher in the STR cohort compared with the GTR group (p = 0.00175). Seven of the 9 STR patients (77.8%) underwent reoperation for recurrence at a median of 32 months from the index operation, while no patients required reoperation after GTR, for an overall reoperation rate of 25%. CONCLUSIONS: Findings of this study emphasize the importance of tumor size and location-particularly involvement of the sacral canal-in determining resectability. Reoperation for recurrence was necessary in 78% of patients with subtotally resected tumors; none of the patients who underwent GTR required reoperation. Most patients had stable neurological status postoperatively.

Endoscopic Reconstruction of the Anterior Skull Base Following Tumor Resection: Application of a Novel Bioabsorbable Plate.

OBJECTIVE: Endoscopic repair of skull base defects is required following resection of intracranial pathology via the endoscopic endonasal approach (EEA). Many closure techniques have been described, but choosing between techniques remains controversial. We report outcomes of 560 EEA procedures of skull base reconstruction performed on 508 patients over a 15-year-period. Halfway through this period, we adopted the use of a rigid, bioabsorbable extrasellar plate for reconstruction, enabling a comparison between this technique and those used previously. METHODS: All patients undergoing EEA from 2005 to 2019 at our institution were retrospectively reviewed. Demographic information, surgical pathology, tumor dimensions and radiographic features, reconstructive technique, and patient-related outcomes were collected and analyzed with univariate and multivariate statistical modeling. RESULTS: Five-hundred sixty procedures were performed on 508 patients. The series complication rate was 8.2%. Overall, cerebrospinal fluid (CSF) leak rate was 5.0% but varied significantly across closure techniques (p < 0.001). Critically, the CSF leak rate in the 272 cases prior to our 2013 adoption of the Resorb-X Plate (RXP) was 8.5%, whereas leak rate in the subsequent 288 cases was 1.7%. RXP was protective against CSF leak (p = 0.001), whereas gross total resection (GTR) correlated with increased leak rate (p = 0.001). Patient BMI was significantly associated with risk of leak (p = 0.047). Other variables did not impact leak risk. CONCLUSION: Reconstructive technique, extent of resection, and patient BMI significantly contributed to CSF leak rate. GTR was associated with increased leak risk while the RXP was protective. The bioabsorbable RXP is an effective option for rigid skull base repair with comparatively few complications. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:1092-1098, 2023.

Reduction of sporadic and neurofibromatosis type 2-associated vestibular schwannoma growth in vitro and in vivo after treatment with the c-Jun N-terminal kinase inhibitor AS602801.

OBJECTIVE: Vestibular schwannomas (VSs) are benign nerve sheath tumors that result from mutation in the tumor suppressor gene NF2, with functional loss of the protein merlin. The authors have previously shown that c-Jun N-terminal kinase (JNK) is constitutively active in human VS cells and plays a central role in their survival by suppressing accumulation of mitochondrial superoxides, implicating JNK inhibitors as a potential systemic treatment for VS. Thus, the authors hypothesized that the adenosine 5'-triphosphate-competitive JNK inhibitor AS602801 would demonstrate antitumor activity in multiple VS models. METHODS: Treatment with AS602801 was tested in primary human VS cultures, human VS xenografts, and a genetic mouse model of schwannoma (Postn-Cre;Nf2flox/flox). Primary human VS cell cultures were established from freshly obtained surgical tumor specimens; treatment group media was enriched with AS602801. VS xenograft tumors were established in male athymic nude mice from freshly collected human tumor. Four weeks postimplantation, a pretreatment MRI scan was obtained, followed by 65 days of AS602801 (n = 18) or vehicle control (n = 19) treatment. Posttreatment MRI scans were used to measure final tumor volume. Tumors were then harvested. Finally, Postn-Cre;Nf2flox/flox mice were treated with AS602801 (n = 10) or a vehicle (n = 13) for 65 days. Posttreatment auditory brainstem responses were obtained. Dorsal root ganglia from Postn-Cre;Nf2flox/flox mice were then harvested. In all models, schwannoma identity was confirmed with anti-S100 staining, cell proliferation was measured with the EdU assay, and cell death was measured with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining. All protocols were approved by the local institutional review board and Institutional Animal Care and Use Committees. RESULTS: Treatment with AS602801 decreased cell proliferation and increased apoptosis in primary human VS cultures. The systemic administration of AS602801 in mice with human VS xenografts reduced tumor volume and cell proliferation. Last, the AS602801-treated Postn-Cre;Nf2flox/flox mice demonstrated decreased cell proliferation in glial cells in the dorsal root ganglia. However, AS602801 did not significantly delay hearing loss in Postn-Cre;Nf2flox/flox mice up to 3 months posttreatment. CONCLUSIONS: The data suggest that JNK inhibition with AS602801 suppresses growth of sporadic and neurofibromatosis type 2-associated VSs. As such, AS602801 is a potential systemic therapy for VS and warrants further investigation.

Spinal Meningioma in Adults: Imaging Characteristics, Surgical Outcomes, and Risk Factors for Recurrence.

OBJECTIVE: Although spinal meningiomas (SMs) are associated with overall long tumor-free survival, SMs can recur. This study analyzed factors associated with complications, misdiagnosis, and recurrence of SMs. METHODS: We reviewed patient demographics; radiographic characteristics of patients with SMs, including level, location within the canal, and size; surgical resection; pathology; and recurrence. RESULTS: The study included 64 women and 10 men (74 SMs). Of patients, 64 showed no recurrence after surgery with a median (range) follow-up of 17 (1-99) months. Recurrence was identified in 10 patients (13.5%) during a median (range) follow-up of 66 (25-230) months. There was no significant difference in sex between the recurrence and no recurrence cohorts. Patients in the recurrence cohort were significantly younger (median [range] age 58 [35-70] years) than patients in the no recurrence cohort (median [range] age 69 [18-93] years; P = 0.0091). There was significant predilection for foraminal locations in the recurrence cohort (P < 0.001) compared with the no recurrence cohort. SM was correctly identified on preoperative magnetic resonance imaging or computed tomography myelography in 62 of 64 tumors (96.9%) in the no recurrence cohort, but in only 6 of 10 tumors (60%) in the recurrence cohort (P < 0.001). CONCLUSIONS: In 74 patients with SMs, a preponderance of female patients and a predilection of tumors for the thoracic spine were shown. Recurrence was significantly more common in younger than older patients. Risk factors for recurrence included larger tumors, foraminal location, and en plaque lesions. Patients who developed recurrence were significantly more likely to have been misdiagnosed on preoperative imaging with nerve sheath tumors or lymphoma.

The biological underpinnings of radiation therapy for vestibular schwannomas: Review of the literature.

OBJECTIVE: Radiation therapy is a mainstay in the treatment of numerous neoplasms. Numerous publications have reported good clinical outcomes for primary radiation therapy for Vestibular Schwannomas (VS). However, there are relatively few pathologic specimens of VSs available to evaluate post-radiation, which has led to a relative dearth in research on the cellular mechanisms underlying the effects of radiation therapy on VSs. METHODS: Here we review the latest literature on the complex biological effects of radiation therapy on these benign tumors-including resistance to oxidative stress, mechanisms of DNA damage repair, alterations in normal growth factor pathways, changes in surrounding vasculature, and alterations in immune responses following radiation. RESULTS: Although VSs are highly radioresistant, radiotherapy is often successful in arresting their growth. CONCLUSION: By better understanding the mechanisms underlying these effects, we could potentially harness such mechanisms in the future to potentiate the clinical effects of radiotherapy on VSs. LEVEL OF EVIDENCE: N/A.

Visual and Hormone Outcomes in Pituitary Apoplexy: Results of a Single Surgeon, Single Institution 15-Year Retrospective Review and Pooled Data Analysis.

Introduction Pituitary apoplexy commonly presents with visual and hormonal deficits. While traditionally regarded as an emergency, there have been increasing trends toward conservative management. Our institutional practice consists of early surgery; therefore, we reviewed our series evaluating vision outcomes, hormone function, and complications compared with the present literature. Methods We retrospectively reviewed our institution's medical records to identify pituitary apoplexy patients who were treated via the endoscopic endonasal approach by a single neurosurgeon (senior author). We recorded basic demographics, radiographic and operative features, and preoperative and postoperative vision and hormone status. Univariate and multivariate statistical analyses were performed. Pooled data analysis of visual outcomes in the current literature using Bayesian inference was performed. Results We identified 44 patients with histologically confirmed pituitary apoplexy treated by endoscopic transsphenoidal decompression; 77% were treated within 24 hours of presentation. Total 45% had cranial nerve (CN) palsy, 36% anopsia, and 20% had visual acuity deficits. Postoperatively, 100% of CN palsies improved, 81% of anopsias improved, and 66.7% of visual acuity deficits improved. Long-lasting panhypopituitarism (25%) and hypothyrodism (22%) were common. Cavernous sinus involvement predicted residual tumor ( p = 0.006). Pooled Bayesian inference showed 30% improvement in vision outcomes with surgical management compared with medical management with a number needed to treat of 3.3. Conclusion Early surgery for pituitary apoplexy was associated with excellent visual outcomes and the need for long-term hormone replacement is common. Cavernous sinus involvement is an independent predictor of residual tumor. Pooled statistical analysis favors aggressive surgical management of apoplexy for improved visual outcomes.

Risk Factors and Survival Analysis of Spinal Cord Stimulator Explantation.

OBJECTIVE: The treatment failure rate for spinal cord stimulators (SCS) remains unacceptably high, with reports of removal in up to 30% of patients. The purpose of this study is to perform survival and multivariate regression analyses of patients who have undergone SCS explantation in order to identify patient characteristics that may predict treatment failure. MATERIALS AND METHODS: We identified 253 patients who underwent SCS placement using current procedural terminology codes in a private health insurance data base spanning 2003-2016. Patient demographics, opioid use, surgical indications, as well as comorbidities were noted. At least 6 months of continuous claims data before and after implantation were required for inclusion. Patients who underwent explantation were defined as those who underwent removal without replacement within 90 days and had at least 90 days of continuous insurance eligibility following removal. Those who underwent removal for infectious reasons were identified with corresponding diagnosis codes. RESULTS: Of the 252 patients who met the inclusion criteria, 17 (6.7%) underwent SCS explantation. Median follow-up time was 2.0 years. Of those who had their system explanted, six patients (2.8%) had their systems removed for infection and 11 (4.3%) for noninfectious reasons. Bivariate analysis revealed that younger age and tobacco use were associated with an increased likelihood of explantation. The Cox proportional hazards analysis demonstrated that younger age, tobacco use, and the presence of "other" mental health disorders were predictive of explantation. CONCLUSIONS: In a cohort of SCS patients from multiple institutions, this study demonstrates that explantation for noninfectious reasons is more likely in younger patients, tobacco users, and those with certain psychiatric conditions. With an estimated 10% of patients opting to have their devices removed within 5 years of implantation, refining the ability of clinicians to predict who will see benefit from SCS treatment remains necessary.

Predictors of Reduced Opioid Use With Spinal Cord Stimulation in Patients With Chronic Opioid Use.

OBJECTIVES: Spinal cord stimulation (SCS) has gained traction as an alternative to chronic opioid therapy in light of the opioid crisis. Prior reports vary widely in their estimates of its effect on opioid consumption. We therefore aimed to address the following questions: 1) Does chronic opioid use change after SCS? 2) Which patient characteristics predict reduced opioid consumption after SCS? MATERIALS AND METHODS: Claims from a private health insurance company were used to identify patients with SCS implantation from 2003 to 2014. We required 12 months of continuous data before and after surgery (i.e., a minimum total observation period of two years), and at least two opioid prescription fills in the six months before surgery. Daily morphine equivalent dose (MED) was calculated from prescription medication claims. Diagnosis codes identified common comorbidities. RESULTS: Hundred forty-five patients met inclusion criteria. MED of 65 was the most statistically meaningful preoperative dose threshold. Approximately half of patients decreased opioid use >20% after SCS implantation. Logistic regression analysis revealed age (p = 0.0362), gender (p = 0.0076), and preoperative daily MED < 65 (p = 0.0322) as predictors of meaningful reduction, which was defined as a 20% reduction in MED. CONCLUSIONS: With only half of chronic opioid users demonstrating meaningful opioid reduction after SCS implantation, we demonstrate that current SCS technology does not reliably help a larger number of patients reduce opioid usage. Women, older age, and preoperative MED < 65 are predictive of meaningful opioid reduction but only one of these is modifiable. As not all patients saw benefit from their therapies, there is still much room for improvement in the treatment of refractory chronic pain that is associated with failed back surgery syndrome and chronic regional pain syndrome.

Dural Ectasia in Neurofibromatosis 1: Case Series, Management, and Review.

BACKGROUND: The natural history and management of dural ectasia in Neurofibromatosis 1 (NF1) is still largely unknown. Dural ectasias are one of the common clinical manifestations of NF1; however, the treatment options for dural ectasias remain unstudied. OBJECTIVE: To investigate the natural history, diagnosis, management, and outcome of the largest case series of patients with NF1-associated dural ectasia to date. METHODS: Records from our NF1 clinic were reviewed to identify NF1 patients with computed tomography or magnetic resonance imaging evidence of dural ectasia(s) to determine their clinical course. Demographics, symptoms, radiographic and histopathologic findings, treatment, and clinical course were assessed. RESULTS: Thirty-four of 37 patients were managed without surgery. Of the 18 initially asymptomatic patients, 5 (27.8%) progressed to symptoms attributable to a dural ectasia (onset of 2.7% per patient-year). Three patients required surgical intervention because of extraspinal mass effect. All 3 initially improved but had symptom recurrence within 2 yr. Reoperation involved shunt placement for cerebrospinal fluid (CSF) diversion. On imaging review, 26 (76.5%) of the nonsurgical patients harbored an associated nearby plexiform neurofibroma. Pathology of one surgical case revealed dural infiltration by diffuse neurofibroma. CONCLUSION: Using the largest NF1-associated dural ectasia group to date, we report the first symptom-onset rate for nonsurgical patients. In the few cases requiring surgery for decompression, primary resection, and patching of ectasias failed, subsequently requiring CSF shunting. We demonstrate imaging evidence of nearby plexiform neurofibroma in a majority of cases, which, when combined with histopathology, provides a novel explanation for the formation of dural ectasias.

National trends in the diagnosis and repair of SLAP lesions in the United States.

BACKGROUND: Since superior labrum anterior-to-posterior (SLAP) tear was introduced as an International Classification of Diseases-Ninth Revision, Clinical Modification diagnosis in 1994, awareness, diagnosis, and surgical treatment of this disorder has increased. Here, we aim to clarify trends in the frequency of SLAP tear diagnosis and arthroscopic SLAP repair surgery in the United States. METHODS: Using private insurance claims from 2003 to 2013 in MarketScan (approximately 55 million Americans), we identified patients with SLAP tear diagnosis or arthroscopic SLAP repair surgery. Population-based rates of SLAP diagnosis and related shoulder procedures were calculated. RESULTS: A total of 329,643 patients in the MarketScan database received a SLAP tear diagnosis. In all, 62.8% underwent some form of shoulder surgery after diagnosis. SLAP diagnosis increased from 28.0 per 100,000 in 2003 to 142.4 per 100,000 in 2013 (p < 0.0001); the rate of shoulder surgery in these patients increased from 20.1 per 100,000 in 2003 to 74.1 per 100,000 in 2013 (p < 0.0001). However, the percentage of patients with SLAP tears who got shoulder surgery decreased (p < 0.0001). In 2003, almost no patient got biceps tenodesis for SLAP tears; by 2013, 18.1% of surgeries for SLAP tear were biceps tenodesis. Isolated arthroscopic SLAP repairs peaked in 2009 at 28.4 per 100,000 and stabilized thereafter. CONCLUSION: We confirmed prior reports that SLAP diagnosis increased from 2003 to 2013, although the percentage of these patients who underwent surgery decreased over this period. Arthroscopic SLAP repair doubled but then plateaued after 2009. Biceps tenodesis now accounts for a substantial portion of surgeries for SLAP tear. This may reflect an improved understanding of superior labrum anatomy and biomechanics.

Not All SLAPs Are Created Equal: A Comparison of Patients with Planned and Incidental SLAP Repair Procedures.

BACKGROUND: Epidemiological studies have shown a progressive increase in the rate of superior labrum anterior-posterior (SLAP) repair surgery after the year 2000. However, it is not clear whether this is due to increased recognition of isolated SLAP tears or increased SLAP repair performed secondarily during arthroscopy for other purposes. HYPOTHESIS/PURPOSE: We hypothesized that both isolated SLAP repair and secondary SLAP repair increased with time and that patient age influenced the pathway to SLAP diagnosis and surgery-such that younger patients were more likely to have isolated SLAP repair surgery after being diagnosed in clinic. STUDY DESIGN: Descriptive epidemiology study. METHODS: Data were obtained from the MarketScan database from 2003 to 2013. CPT and ICD-9 codes were used to identify SLAP surgery patients and concomitant procedures. The timing of SLAP diagnosis relative to surgery was used to determine whether the injury was recognized preoperatively. RESULTS: 64,497 SLAP surgery patients were included. Preoperative SLAP diagnosis increased from 17.1% in 2003 to 44.6% in 2013. Patients diagnosed preoperatively were younger and had fewer concomitant procedures. Increasing age and concomitant rotator cuff tear (RCT) repair corresponded to lower odds of preoperative SLAP diagnosis. DISCUSSION: Younger patients were more likely to have their SLAP tear diagnosed prior to surgery. Those diagnosed before surgery had fewer simultaneous procedures during their operations, suggesting that SLAP repair was more likely the primary operation. From 2003 to 2013, SLAP tears were increasingly recognized in the preoperative setting.

A Report of 2 Cases of Brainstem Hemorrhage After Suboccipital Craniectomy for Chiari Decompression.

BACKGROUND AND IMPORTANCE: Decompression surgery for Chiari malformation is known to have very low procedure-related complications. There has been no report of post-Chiari malformation decompression surgery development of brainstem hemorrhage. We report 2 post-Chiari decompression surgery brainstem hemorrhage cases with 2-yr follow-up. CLINICAL PRESENTATION: Two cases were reviewed in which patients underwent uncomplicated suboccipital craniectomy with expansive autologous pericranium duraplasty for Chiari decompression. Postoperatively, both patients awoke with hemibody sensory and motor deficits. Immediate postoperative magnetic resonance imaging revealed a small hemorrhage within the dorsal medulla in both cases. Follow-up imaging shows resolution along with near complete clinical recovery of deficits. CONCLUSION: These cases demonstrate a rare postdecompression surgery-related complication in Chiari malformation. We hypothesize that these hemorrhages may occur from the rapid drainage of cerebrospinal fluid resulting in a loss of positive pressure, allowing a low-pressure hemorrhage to occur. Given that these hemorrhages are of low pressure, recovery is excellent.

Lovastatin inhibits T-cell proliferation while preserving the cytolytic function of EBV, CMV, and MART-1-specific CTLs.

Statin treatment has been shown to reduce graft-versus-host disease while preserving graft-versus-tumor effect in allogeneic stem cell transplantation. Herein, we investigated whether lovastatin treatment affects the function of human cytolytic T lymphocytes (CTLs). Upon T-cell receptor stimulation, lovastatin significantly inhibited the proliferation of both CD4+ and CD8+ T cells from healthy donors whereas their intracellular cytokine production including interferon-γ and tumor necrosis factor-α remained the same with a slight decrease of interleukin-2. Moreover, the specific lysis of target cells by CTL lines derived from patients and normal donors specific for Epstein-Barr virus-encoded antigen latent membrane protein-2 or cytomegalovirus-encoded antigen pp65 was uncompromised in the presence of lovastatin. In addition, we evaluated the effect of lovastatin on the proliferation and effector function of the CD8+ tumor-infiltrating lymphocytes (TILs) derived from melanoma patients specific for MART-1 antigen. Lovastatin significantly reduced the expansion of antigen-specific TILs upon MART-1 stimulation. However, the effector function of TILs, including the specific lysis of target cells and secretion of cytokine interferon-γ, remained intact with lovastatin treatment. Taken together, these data demonstrated that lovastatin inhibits the proliferation of Epstein-Barr virus, cytomegalovirus, and MART-1-specific CTLs without affecting cytolytic capacity. The differential effect of lovastatin on the proliferation versus cytotoxicity of CTLs might shed some light on elucidating the possible mechanisms of graft-versus-host disease and graft-versus-tumor effect elicited by alloimmune responses.