Focused versus conventional radiotherapy in spinal oncology: is there any difference in fusion rates and pseudoarthrosis?

INTRODUCTION: Radiotherapy is considered standard of care for adjuvant peri-operative treatment of many spinal tumors, including those with instrumented fusion. Unfortunately, radiation treatment has been linked to increased risk of pseudoarthrosis. Newer focused radiotherapy strategies with enhanced conformality could offer improved fusion rates for these patients, but this has not been confirmed. METHODS: We performed a retrospective analysis of patients at three tertiary care academic institutions with primary and secondary spinal malignancies that underwent resection, instrumented fusion, and peri-operative radiotherapy. Two board certified neuro-radiologists used the Lenke fusion score to grade fusion status at 6 and 12-months after surgery. Secondary outcomes included clinical pseudoarthrosis, wound complications, the effect of radiation timing and radiobiological dose delivered, the use of photons versus protons, tumor type, tumor location, and use of autograft on fusion outcomes. RESULTS: After review of 1252 spinal tumor patients, there were 60 patients with at least 6 months follow-up that were included in our analyses. Twenty-five of these patients received focused radiotherapy, 20 patients received conventional radiotherapy, and 15 patients were treated with protons. There was no significant difference between the groups for covariates such as smoking status, obesity, diabetes, intraoperative use of autograft, and use of peri-operative chemotherapy. There was a significantly higher rate of fusion for patients treated with focused radiotherapy compared to those treated with conventional radiotherapy at 6-months (64.0% versus 30.0%, Odds ratio: 4.15, p = 0.036) and 12-months (80.0% versus 42.1%, OR: 5.50, p = 0.022). There was a significantly higher rate of clinical pseudoarthrosis in the conventional radiotherapy cohort compared to patients in the focused radiotherapy cohort (19.1% versus 0%, p = 0.037). There was no difference in fusion outcomes for any of the secondary outcomes except for use of autograft. The use of intra-operative autograft was associated with an improved fusion at 12-months (66.7% versus 37.5%, OR: 3.33, p = 0.043). CONCLUSION: Focused radiotherapy may be associated with an improved rate of fusion and clinical pseudoarthrosis when compared to conventional radiation delivery strategies in patients with spinal tumors. Use of autograft at the time of surgery may be associated with improved 12-month fusion rates. Further large-scale prospective and randomized controlled studies are needed to better stratify the effects of radiation delivery modality in these patients.

Spinal cord high-grade infiltrating gliomas in adults: clinico-pathological and molecular evaluation.

Primary high-grade infiltrating gliomas of the spinal cord are rare, with prior series including limited numbers of cases and reporting poor outcomes. Additionally, the molecular profile of high-grade infiltrating gliomas of the spinal cord has not been well characterized. We identified 13 adult patients whose surgery had been performed at our institution over a 26-year-period. Radiologically, nine cases harbored regions of post-contrast enhancement. Existing slides were reviewed, and when sufficient tissue was available, immunohistochemical stains (IDH1-R132H, H3-K27M, H3K27-me3, ATRX, p53 and BRAF-V600E), and a targeted 150-gene neuro-oncology next-generation sequencing panel were performed. The 13 patients included 11 men and 2 women with a median age of 38 years (range = 18-69). Histologically, all were consistent with an infiltrating astrocytoma corresponding to 2016 WHO grades III (n = 5) and IV (n = 8). By immunohistochemistry, six cases were positive for H3K27M, all showing concomitant loss of H3K27-me3. Next-generation sequencing was successfully performed in ten cases. Next-generation sequencing studies were successfully performed in four of the cases positive for H3K27M by immunohistochemistry, and all were confirmed as H3F3A K27M-mutant. Additional recurrent mutations identified included those of TERT promoter (n = 3), TP53 (n = 5), PPM1D (n = 3), NF1 (n = 3), ATRX (n = 2), and PIK3CA (n = 2). No HIST1H3B, HIST1H3C, IDH1, IDH2, or BRAF mutations were detected. Ten patients have died since first surgery, with a median survival of 13 months and 1 year of 46%. Median survival was 48.5 months for H3K27M-positive cases, compared to 1 month for those with TERT promoter mutation and 77 months for those harboring neither (p = 0.019). Median survival for cases with TP53 mutations was 11.5 months and for those with PPM1D mutations was 84 months. Our findings suggest that high-grade infiltrating gliomas of the spinal cord in adults represent a heterogeneous group of tumors, with variable outcomes possibly related to their molecular profiles.

Variation in management of spinal gliobastoma multiforme: results from a national cancer registry.

PURPOSE: Primary glioblastoma of the spinal cord (spinal GBM) is a rare central nervous system tumor, relative to its cranial counterpart (cranial GBM). Our current knowledge of spinal GBM epidemiology, tumor characteristics and treatment are insufficient and mostly based on single-institution case series. METHODS: All patients diagnosed with grade-4 GBM from 2004 to 2014 were queried from the National Cancer Database. Chi square analysis was used to compare presenting characteristics while Kaplan-Meier and Cox regression analyses were employed for survival analyses. RESULTS: Total 103,496 patients with cranial GBM and 190 patients with spinal GBM were analyzed. Median survival for spinal GBM was found to be higher compared to cranial GBM (p = 0.07). Spinal GBM patients had significant better survival in 18 to 65 years age group than < 18 years and > 65 years age group (p = 0.003). Overall survival time for 95 spinal GBM patients with available treatment data was not statistically different among the four treatment modalities (radiation with or without chemotherapy, surgery alone, surgery with adjuvant therapy, and palliative therapy; p = 0.28).On multivariable analysis, < 18 years age group was associated with improved survival (HR 0.50, 95% CI 0.23-1.00, p = 0.046), while tumor extension was associated with poor survival (HR 2.71, 95% CI 1.04-6.22, p = 0.041). Interestingly surgery with adjuvant therapy was unable to show increase survival compared to other treatment modalities. CONCLUSIONS: Our study adds to the growing literature on spinal GBM with a focus on comparative trends with cranial GBM and outcomes with different treatment modalities.

Standardized text messages improve 30-day patient follow-up for ACS pediatric NSQIP cases.

PURPOSE: Thirty-day follow-up is a critical and challenging component of the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP). We hypothesized the simplicity and immediacy of text messaging would increase response rates while reducing workload. METHODS: For 6 months, text messages were the primary form of contact for first and second follow-up attempts. If no response, a phone call was made. Results of this protocol were compared to the previous 6 months when phone calls were the primary method. RESULTS: The text message (TM) group had 298 cases and phone call (PC) group had 354. The first contact was successful in 63.8% of the TM group compared to 47.5% of the PC group. The second contact was successful in 15.4% (TM) and 16.9% (PC). In the third attempt, 3.0% answered the call in the TM group versus 9.3% in the PC group. Some families remained unreachable: 17.8% in TM group and 26.3% in PC group (p = 0.01). When totaled, time spent to obtain caregivers' responses was over five times higher in the PC group (910 min) than the TM group (173 min) (p = 0.005). CONCLUSION: Patient follow-up using text messaging has improved our follow-up rate while decreasing workload.

High fat diet induces pre-type 2 diabetes with regional changes in corneal sensory nerves and altered P2X7 expression and localization.

Type 2 diabetes is one of the leading pathologies that increases the risk of improper wound healing. Obesity has become a major risk factor for this disease that is now considered to be the 4th highest cause of preventable blindness according to the World Health Organization. The cornea is the most densely innervated structure in the human body and senses even the slightest injury. In diabetes, decreased corneal sensitivity secondary to diabetic peripheral neuropathy can lead to increased corneal abrasion, ulceration, and even blindness. In this study, a diet induced obesity (DIO) mouse model of pre-Type 2 diabetes was used to characterize changes in sensory nerves and P2X7, a purinoreceptor, a pain receptor, and an ion channel that is expressed in a number of tissues. Since our previous studies demonstrated that P2X7 mRNA was significantly elevated in diabetic human corneas, we examined P2X7 expression and localization in the DIO murine model at various times after being fed a high fat diet. Fifteen weeks after onset of diet, we found that there was a significant decrease in the density of sub-basal nerves in the DIO mice that was associated with an increase in tortuosity and a decrease in diameter. In addition, P2X7 mRNA expression was significantly greater in the corneal epithelium of DIO mice, and the increase in transcript was enhanced in the central migrating and peripheral regions after injury. Interestingly, confocal microscopy and thresholding analysis revealed that there was a significant increase in P2X7 distal to the injury, which contrasted with a decrease in P2X7-expressing stromal sensory nerves. Therefore, we hypothesize that the P2X7 receptor acts to sense changes at the leading edge following an epithelial abrasion, and this fine-tuned regulation is lost during the onset of diabetes. Further understanding of the corneal changes that occur in diabetes can help us better monitor progression of diabetic complications, as well as develop new therapeutics for the treatment of diabetic corneal dysfunction.

Evaluating osteoporosis and bone quality in the aging spine: modern considerations for surgical management in the geriatric population.

Surgical management paradigms of spinal pathologies in the aging population carry inherent substantial risks, with surgical complications being more prevalent among patients with osteoporosis compared to those with normal bone mineral density. In this narrative review, we aim to highlight important clinical understanding and considerations in perioperative evaluation and management of patients elected to undergo spinal surgery. Osteoporosis is a well-defined risk factor for mechanical complications following spinal surgery, and as such, perioperative optimization of bone health in the setting of surgery for geriatric patients remains a critical research area alongside intraoperative surgical augmentation techniques. Surgical techniques to circumvent challenges with instrumentation of poor bone mineral density have included augmentation of pedicle screw fixation, including segmental bicortical screw fixation techniques, cement augmentation with fenestrated screws, or use of expandable pedicle screws to improve bone-implant interface. Judicious selection of treatment modalities and subsequent perioperative optimization is paramount to minimize surgical complications. Contemporary guidelines and evolving paradigms in perioperative evaluation, optimization, and management of the aging spine include the advent of quantitatively evaluating computed tomography (CT) via assessment of the magnitude of Hounsfield units. Prescribing pharmacotherapeutic agents and monitoring bone health requires a multidisciplinary team approach, including endocrinologists and geriatricians to coordinate high-quality care for advanced-age patients who require surgical management of their spinal disorders.

Surgical Anatomy of the Microscopic and Endoscopic Transorbital Approach to the Middle Fossa and Cavernous Sinus: Anatomo-Radiological Study with Clinical Applications.

BACKGROUND: The transorbital approaches (TOAs) have acquired growing notoriety, thanks to their ability to offer alternative corridors to the skull base. However, the limited access and the unfamiliarity with this surgical perspective make recognition of key landmarks difficult, especially for less experienced surgeons. The study wants to offer a detailed description of the anatomy to comprehend the potential and limitations of TOAs. METHODS: Measurements of the orbit region and the surrounding areas were performed on two hundred high-resolution CT scans and thirty-nine dry skulls. Five specimens were dissected to illustrate the TOA, and one was used to perform the extradural clinoidectomy. Three clinical cases highlighted the surgical applications. RESULTS: A step-by-step description of the key steps of the TOA was proposed and a comparison with the transcranial anterior clinoidectomy was discussed. The mean work distance was 6.1 ± 0.4 cm, and the lateral working angle increased 20 ± 5.4° after removing the lateral orbital rim. CONCLUSIONS: TOAs are indicated in selected cases when tumor involves the lateral portion of the cavernous sinus or the middle skull base, obtaining a direct decompression of the optic nerve and avoiding excessive manipulation of the neurovascular structures. Comprehension of surgical anatomy of the orbit and its surrounding structures is essential to safely perform these approaches.

Image-localized biopsy mapping of brain tumor heterogeneity: A single-center study protocol.

Brain cancers pose a novel set of difficulties due to the limited accessibility of human brain tumor tissue. For this reason, clinical decision-making relies heavily on MR imaging interpretation, yet the mapping between MRI features and underlying biology remains ambiguous. Standard (clinical) tissue sampling fails to capture the full heterogeneity of the disease. Biopsies are required to obtain a pathological diagnosis and are predominantly taken from the tumor core, which often has different traits to the surrounding invasive tumor that typically leads to recurrent disease. One approach to solving this issue is to characterize the spatial heterogeneity of molecular, genetic, and cellular features of glioma through the intraoperative collection of multiple image-localized biopsy samples paired with multi-parametric MRIs. We have adopted this approach and are currently actively enrolling patients for our 'Image-Based Mapping of Brain Tumors' study. Patients are eligible for this research study (IRB #16-002424) if they are 18 years or older and undergoing surgical intervention for a brain lesion. Once identified, candidate patients receive dynamic susceptibility contrast (DSC) perfusion MRI and diffusion tensor imaging (DTI), in addition to standard sequences (T1, T1Gd, T2, T2-FLAIR) at their presurgical scan. During surgery, sample anatomical locations are tracked using neuronavigation. The collected specimens from this research study are used to capture the intra-tumoral heterogeneity across brain tumors including quantification of genetic aberrations through whole-exome and RNA sequencing as well as other tissue analysis techniques. To date, these data (made available through a public portal) have been used to generate, test, and validate predictive regional maps of the spatial distribution of tumor cell density and/or treatment-related key genetic marker status to identify biopsy and/or treatment targets based on insight from the entire tumor makeup. This type of methodology, when delivered within clinically feasible time frames, has the potential to further inform medical decision-making by improving surgical intervention, radiation, and targeted drug therapy for patients with glioma.

Anterior Thoracic Diskectomy and Fusion: Surgical Technique and Anatomic Considerations.

Ossification of the posterior longitudinal ligament (OPLL) is a rare condition that can lead to progressive spinal cord compression.1 Currently, surgical decompression remains the optimal treatment in symptomatic patients.2,3 In cases with significant thoracic stenosis and concern for ventral erosion of the dura, an anterior approach may be necessary for direct decompression.4 In Video 1, we demonstrate the successful application of a multidisciplinary approach for surgical resection of a large OPLL lesion located at the T2-3 disk space. A 37-year-old female with medical history significant for rickets presented a year after a fall with bilateral lower extremity paraparesis and saddle anesthesia. Exposure consisted of a manubrial window, followed by thoracic diskectomy and fusion with drilling of the calcified posterior longitudinal ligament. Major steps within this video include 1) a summary of the patient presentation and preoperative imaging, 2) exposure of thoracic vertebrae via a manubrial window approach, 3) thoracic diskectomy and fusion with take-down of calcified posterior longitudinal ligament, and 4) a review of the postoperative imaging. The patient tolerated the procedure well with immediate relief of symptoms and was subsequently discharged on postoperative day 1 with no complications. This operative video illustrates the technical steps and capabilities of an anterior approach, achieving near-complete gross total resection of an OPLL lesion using a multidisciplinary approach. The patient consented to this procedure.

Surgical treatment of spinal cord compression due to Hirayama disease: illustrative case.

BACKGROUND: Hirayama disease (HD), also known as juvenile spinal muscular atrophy, is a rare condition in which flexion of the cervical neck causes compression and ischemic changes to the anterior horns of the spinal cord. Here the authors presented the first reported case of HD in North America that was successfully treated via surgical intervention. OBSERVATIONS: The patient was a 15-year boy with insidious onset upper limb weakness and atrophy. His findings were a classic presentation of HD although his complex history and relative rarity of the disease caused him to remain undiagnosed for months. After conservative management via cervical collar failed, the patient was successfully treated via C5-C7 anterior cervical discectomy and fusion. The patient's symptoms stabilized by the 3-month follow-up. LESSONS: The diagnosis of HD is easy to miss because of the lack of reporting and widespread knowledge of this condition in North America. Thus, when presented with a case of insidious onset limb weakness in a juvenile patient, HD should be placed on the differential list and verified with cervical flexion magnetic resonance imaging. Additionally, surgical intervention should be considered a safe and effective option for HD when conservative methods have failed.

Recent Trends in Medicare Utilization and Reimbursement for Lumbar Fusion Procedures: 2000-2019.

OBJECTIVE: Lumbar fusions are commonly performed spinal procedures. Despite this, publicly available lumbar fusion procedural and monetary data are sparse. This study aimed to evaluate trends in utilization and reimbursement for Medicare patients from 2000-2019. METHODS: Medicare National Summary Data Files were used. Data were collected for true physician reimbursements and procedural rates for posterolateral fusion, anterior lumbar interbody fusion, posterior lumbar interbody fusion (PLIF), and combined PLIF and posterolateral fusion from 2000-2019. Reimbursement was adjusted to inflation utilizing the 2019 Consumer Price Index. RESULTS: From 2000-2019, 1,266,942 lumbar fusion procedures were billed to Medicare Part B. Annual number of lumbar interbody fusion procedures increased by 57,740 procedures (+95%) from 61,017 in 2000 to 118,757 in 2019. This change in annual volume varied by procedure type, with posterolateral fusion increasing from 24,873 procedures in 2000 to 45,665 procedures in 2019 (+20,792, +83.59%), anterior lumbar interbody fusion increasing from 4227 in 2000 to 29,285 procedures in 2019 (+25,058, 592.81%), PLIF increasing from 5579 procedures in 2000 to 5628 procedures in 2019 (+49, +0.88%), and combined PLIF and posterolateral fusion increasing from 26,338 procedures in 2012 to 38,179 procedures in 2019 (+11,841, +44.96%). The mean inflation-adjusted reimbursement decreased for posterolateral fusion from $1662.96 to $1245.85 (-$417.11, -25.08%), anterior lumbar interbody fusion from $1159.45 to $750.33 (-$409.12, -35.29%), PLIF from $1225.02 to $1223.72 (-$1.3, -0.11%), and combined PLIF and posterolateral fusion from $1541.59 per procedure in 2012 to $1467.08 per procedure in 2019. CONCLUSIONS: Lumbar fusions have increased in the last 2 decades, although reimbursement for all procedures has decreased. Knowledge of these trends is important to ensure adequate resource allocation to surgeons as treating lumbar pathologies becomes more common among the aging Medicare population.

A comparison of treating physician versus independent core lab assessments of post-aneurysm treatment imaging outcomes: an analysis of prospectively collected data from a randomized trial.

OBJECTIVE: Aneurysm occlusion has been used as surrogate marker of aneurysm treatment efficacy. Aneurysm occlusion scales are used to evaluate the outcome of endovascular aneurysm treatment and to monitor recurrence. These scales, however, require subjective interpretation of imaging data, which can reduce the utility and reliability of these scales and the validity of clinical studies regarding aneurysm occlusion rates. Use of a core lab with independent blinded reviewers has been implemented to enhance the validity of occlusion rate assessments in clinical trials. The degree of agreement between core labs and treating physicians has not been well studied with prospectively collected data. METHODS: In this study, the authors analyzed data from the Hydrogel Endovascular Aneurysm Treatment (HEAT) trial to assess the interrater agreement between the treating physician and the blinded core lab. The HEAT trial included 600 patients across 46 sites with intracranial aneurysms treated with coiling. The treating site and the core lab independently reviewed immediate postoperative and follow-up imaging (3-12 and 18-24 months, respectively) using the Raymond-Roy occlusion classification (RROC) scale, Meyer scale, and recanalization survey. A post hoc analysis was performed to calculate interrater reliability using Cohen's kappa. Further analysis was performed to assess whether degree of agreement varied on the basis of various factors, including scale used, timing of imaging, size of the aneurysm, imaging modality, location of the aneurysm, dome-to-neck ratio, and rupture status. RESULTS: Minimal interrater agreement was noted between the core lab reviewers and the treating physicians for assessing aneurysm occlusion using the RROC grading scale (k = 0.39, 95% CI 0.38-0.40) and Meyer scale (k = 0.23, 95% CI 0.14-0.38). The degree of agreement between groups was slightly better but still weak for assessing recanalization (k = 0.45, 95% CI 0.38-0.52). Factors that significantly improved degree of agreement were scales with fewer variables, greater time to follow-up, imaging modality (digital subtraction angiography), and wide-neck aneurysms. CONCLUSIONS: Assessment of aneurysm treatment outcome with commonly used aneurysm occlusion scales suffers from risk of poor interrater agreement. This supports the use of independent core labs for validation of outcome data to minimize reporting bias. Use of outcome tools with fewer point categories is likely to provide better interrater reliability. Therefore, the outcome assessment tools are ideal for clinical outcome assessment provided that they are sensitive enough to detect a clinically significant change.

Carotid Artery Injury during Transsphenoidal Pituitary Surgery: Lessons from a 15-Year Modern Microsurgery Cohort.

Background Internal carotid artery (ICA) injury is a rare but potentially catastrophic complication of transsphenoidal resection (TSR) of pituitary tumors, potentially resulting in a host of deficits due to the risk of hemorrhage, ischemia, or even death. The endoscopic endonasal approach (EEA) has gained considerable popularity in the modern era, with few busy neurosurgeons remaining committed to practicing transnasal pituitary microsurgery. Our objective was therefore to characterize the overall incidence of ICA injury in a large, longitudinal, single-surgeon microscopic TSR series conducted during the modern EEA era. Methods Retrospective case series. Results Overall TSR volume by the senior author (F.B.M.) was 817 pituitary tumors during the study period, 2002 to 2017. Within that cohort, two instances of ICA injury were identified (0.2%), including one each with Cushing's disease and acromegaly, both of whom ultimately recovered without residual neurologic deficit. No pediatric injuries were identified. Conclusion Vascular injury is an exceedingly rare complication of transsphenoidal pituitary surgery. Adjuncts to prevent this complication include careful review of the coronal magnetic resonance imaging, identification of the midline, as needed use of the Doppler, and initial caudal opening of the sellar dura. Although potentially disastrous, good neurologic outcomes may be obtained, with immediate judicious packing followed by immediate digital subtraction angiography to assess vessel patency and secondary complications such as pseudoaneurysm.

Impact of Body Mass Index on female fertility and ART outcomes.

As the global mean Body Mass Index (BMI) is on the rise, the importance of understanding exactly how female fertility is impacted by once outlier BMI values, becomes ever more important. Studies have implicated abnormal BMI on the female reproductive system by contributing to anovulation, irregular menses, adverse oocyte quality, endometrial alterations, and hormonal imbalances. These well ultimately result in female infertility, which could complicate natural conception efforts and request considering assisted reproductive technology (ART) in such couples. With an increase in the demand for ART, it is crucial to understand what factors can be altered by the female BMI in order to maximize the opportunity for successful pregnancy. The current manuscript aimed to review the information about the effect of BMI on the female fertility and ART outcomes. The complex nature of the female reproductive system leaves space for multiple factors to adversely affect its processes. Imbalances in the hypothalamus-pituitary-ovarian axis can impede efforts for couples to conceive. Leptin and estrogen are two hormones that have been implicated in regulating BMI as well as reproductive physiology. Lifestyle modifications prior to, and during ART have shown promise in enhancing fecundity. The intricacies in female reproductive system leaves much to the unknown, and often with conflicting results. Further research is required to fully elucidate what aspects of female fertility are influenced by BMI, and how the healthcare provider can facilitate successful outcomes. The current review will enable a better consultation and treatment.

Extraordinary case presentations in pediatric pituitary adenoma: report of 6 cases.

Pediatric pituitary adenomas (PPAs) are rare neoplasms with a propensity for unusual presentations and an aggressive clinical course. Here, the authors describe 6 highly atypical PPAs to highlight this tendency and discuss unexpected management challenges.A 14-year-old girl presented with acute hemiparesis and aphasia. MRI revealed a pituitary macroadenoma causing internal carotid artery invasion/obliteration without acute apoplexy, which was treated via emergent transsphenoidal resection (TSR). Another 14-year-old girl developed precocious galactorrhea due to macroprolactinoma, which was medically managed. Several years later, she re-presented with acute, severe, bitemporal hemianopia during her third trimester of pregnancy, requiring emergent induction of labor followed by TSR. A 13-year-old boy was incidentally diagnosed with a prolactinoma after routine orthodontic radiographs captured a subtly abnormal sella. An 18-year-old male self-diagnosed pituitary gigantism through a school report on pituitary disease. A 17-year-old boy was diagnosed with Cushing disease by his basketball coach, a former endocrinologist. A 12-year-old girl with growth arrest and weight gain was diagnosed with Cushing disease, which was initially treated via TSR but subsequently recurred and ultimately required 12 operations, 5 radiation treatments involving 3 modalities, bilateral adrenalectomy, and chemotherapy. Despite these efforts, she ultimately died from pituitary carcinoma.

Beyond the Learning Curve: Comparison of Microscopic and Endoscopic Incidences of Internal Carotid Injury in a Series of Highly Experienced Operators.

BACKGROUND: As the endoscopic endonasal approach (EEA) has gained popularity as an alternative to microsurgery (MS) for transsphenoidal resection (TSR), numerous studies have attempted to assess the differential risk of internal carotid artery (ICA) injury between the techniques, yet results have been equivocal and contradictory. The aim of this study was to evaluate ICA injury in MS versus EEA among highly experienced neurosurgeons. METHODS: We performed a systematic literature review of publications from 2002-2017 reporting ICA injury outcomes in ≥250 cases using MS or EEA. RESULTS: Seventeen series reporting 11,149 patients were included: 3 MS series, 13 EEA series, and 1 series with adequate samples for each. ICA injury incidences were 0.0%-1.6% in cohorts of 275-3000. MS series documented 5 ICA injuries in 2672 operations, for an overall incidence of 0.2% (range, 0.0%-0.4%), and EEA series reported 30 ICA injuries in 8477 operations, for a 0.4% injury rate (range, 0.0%-1.6%); the difference was nonsignificant (P = 0.25). Increased operative experience was associated with decreased incidence of ICA injury, a finding preserved in the overall study cohort and within discretely examined MS and EEA subgroups (overall r2 = 0.08, MS r2 = 0.23, EEA r2 = 0.07). CONCLUSIONS: ICA injury is the most serious complication of TSR of pituitary neoplasms. Operator inexperience may be a more important risk factor than choice of surgical technique, given the comparably low rates of injury obtained by highly experienced surgeons independent of technique. This emphasizes the need for consolidated care in pituitary centers of excellence, improvement of high-fidelity simulators, and skull base mentorship between senior and junior staff.