Retrospective Review of Surgical Site Infections after Endoscopic Endonasal Sellar and Parasellar Surgery: Multicenter Quality Data from the North American Skull Base Society.

Introduction Transnasal access to the anterior skull base provides a minimally invasive approach for sellar and parasellar masses compared with its open counterparts. The unique microbiome of the sinonasal mucosa provides distinct challenges not encountered with other cranial approaches. The use of antibiotics in these cases has not been standardized, and data remain scarce regarding infectious outcomes. Methods We conducted a multicenter retrospective analysis of shared quality data points for the endoscopic endonasal approach (EEA) for pituitary adenomas, along with other sellar and parasellar region masses that were included by participating institutions. Patient and operative characteristics, perioperative and postoperative antibiotic regimens and their durations, intraoperative and postoperative cerebrospinal fluid leak, and onset of postoperative meningitis and sinusitis were compared. Results Fifteen institutions participated and provided 6 consecutive months' worth of case data. Five hundred ninety-three cases were included in the study, of which 564 were pituitary adenomectomies. The incidences of postoperative meningitis and sinusitis were low (0.67 and 2.87% for all pathologies, respectively; 0.35% meningitis for pituitary adenomas) and did not correlate with any specific antibiotic regimen. Immunocompromised status posed an increased odds of meningitis in pituitary adenomectomies (28.6, 95% confidence interval [1.72-474.4]). Conclusions The results show no clear benefit to postoperative antimicrobial use in EEA, with further larger studies needed.

Developing an Integrated Multidisciplinary Pituitary Management Team.

Interdisciplinary teams have many potential and proven benefits, including decreased burnout, decreased medical errors, increased quality, and leveraging of competing values and skills. Pituitary Tumor Centers of Excellence must have adequate volumes and high-functioning teams in order to provide exceptional, high-value care. Organizational logistics, attentive operations management, facilitated collaboration, and clear communication are key teamwork tools in delivering that care.

Rapid Automated Analysis of Skull Base Tumor Specimens Using Intraoperative Optical Imaging and Artificial Intelligence.

BACKGROUND: Accurate specimen analysis of skull base tumors is essential for providing personalized surgical treatment strategies. Intraoperative specimen interpretation can be challenging because of the wide range of skull base pathologies and lack of intraoperative pathology resources. OBJECTIVE: To develop an independent and parallel intraoperative workflow that can provide rapid and accurate skull base tumor specimen analysis using label-free optical imaging and artificial intelligence. METHODS: We used a fiber laser-based, label-free, nonconsumptive, high-resolution microscopy method (<60 seconds per 1 × 1 mm2), called stimulated Raman histology (SRH), to image a consecutive, multicenter cohort of patients with skull base tumor. SRH images were then used to train a convolutional neural network model using 3 representation learning strategies: cross-entropy, self-supervised contrastive learning, and supervised contrastive learning. Our trained convolutional neural network models were tested on a held-out, multicenter SRH data set. RESULTS: SRH was able to image the diagnostic features of both benign and malignant skull base tumors. Of the 3 representation learning strategies, supervised contrastive learning most effectively learned the distinctive and diagnostic SRH image features for each of the skull base tumor types. In our multicenter testing set, cross-entropy achieved an overall diagnostic accuracy of 91.5%, self-supervised contrastive learning 83.9%, and supervised contrastive learning 96.6%. Our trained model was able to segment tumor-normal margins and detect regions of microscopic tumor infiltration in meningioma SRH images. CONCLUSION: SRH with trained artificial intelligence models can provide rapid and accurate intraoperative analysis of skull base tumor specimens to inform surgical decision-making.

Imaging Errors in Distinguishing Pituitary Adenomas From Other Sellar Lesions.

BACKGROUND: Pituitary adenomas and nonadenomatous lesions in the sellar region may be difficult to distinguish by imaging yet that distinction is critical in guiding management. The nature of the diagnostic errors in this setting has not been well documented. METHODS: Two neurosurgeons and 2 neuroradiologists of differing experience levels viewed deidentified MRIs of 18 nonadenomatous sellar lesions and 21 adenomas. They recorded their diagnoses, the imaging features they used to make those diagnoses, and their confidence in making those diagnoses. RESULTS: Among the 18 nonadenoma cases, 11 (61%) were incorrectly diagnosed as adenoma by at least 1 reader, including Rathke cleft cyst, plasmacytoma, aneurysm, craniopharyngioma, chordoma, Langerhans cell histiocytosis, metastasis, and undifferentiated sinonasal carcinoma. Among the 21 adenoma cases, 8 (38%) were incorrectly diagnosed by at least 1 reader as craniopharyngioma, Rathke cleft cyst, sinonasal carcinoma, hemangioblastoma, and pituitary hyperplasia. Incorrect imaging diagnoses were made with high confidence in 13% of readings. Avoidable errors among the nonadenomatous cases occurred when readers failed to appreciate that the lesion was separate from the pituitary gland. Unavoidable errors in those cases occurred when the lesions were so large that the pituitary gland had been obliterated or the imaging features of a nonadenomatous lesion resembled those of a cystic pituitary adenoma. Avoidable errors in misdiagnosis of adenomas as nonadenomas occurred when readers failed to appreciate features highly characteristic of adenomas. An unavoidable error occurred because a cystic adenoma had features correctly associated with craniopharyngioma. CONCLUSIONS: Errors in imaging differentiation of pituitary adenoma from nonadenomatous lesions occurred often and sometimes with high confidence among a small sample of neurosurgeons and neuroradiologists. In the misdiagnosis of nonadenomatous lesions as adenomas, errors occurred largely from failure to appreciate a separate pituitary gland, but unavoidable errors occurred when large lesions had obliterated this distinguishing feature. In the misdiagnosis of adenomas as nonadenomatous lesions, avoidable errors occurred because readers failed to recognize imaging features more characteristic of adenomas and because cystic adenomas share features with craniopharyngiomas and Rathke cleft cysts. Awareness of these errors should lead to improved management of sellar lesions.

Rapid visual field constriction in a patient with retinitis pigmentosa and pituitary adenoma.

PURPOSE: To report a case of pituitary adenoma in a patient with retinitis pigmentosa (RP) and consequent rapid constriction of the visual field in each eye, which is atypical for either of these pathologies. OBSERVATIONS: A 45-year old male, with a long-standing history of RP, presented with rapid vision loss over 3 months. Examination revealed a severe drop in visual acuity and significant progression of concentric visual field constriction in each eye compared to 3 months prior. MRI revealed a pituitary macroadenoma compressing the optic chiasm. The patient underwent endoscopic trans-sphenoidal resection of the tumor and experienced partial recovery of visual acuity but not visual field. CONCLUSIONS AND IMPORTANCE: The visual field deficit in this patient was atypical for pituitary adenoma or optic neuropathy. The pattern was most consistent with RP, but the rate of progression was not. In a patient with chiasmal pathology in the setting of pre-existing retinopathy, visual field progression may not be limited exclusively to the bitemporal regions. Rapid constriction of the visual field in a patient with RP should prompt a work-up for alternative etiologies which includes neuro-imaging.

Late Surgical Start Time and the Effect on Rates of Complications in a Neurosurgical Population: A Prospective Longitudinal Analysis.

OBJECTIVE: The after-hours effect on postoperative complications has been poorly studied in the neurosurgical literature. A recent retrospective analysis showed that patients with a surgical start time (SST) between 09:01 pm and 07:00 am had a greater risk of complications. This study used a prospective registry to examine the relationship between SST and postoperative complications in a large neurosurgical population. METHODS: We performed a prospective longitudinal cohort analysis of all consecutive adult patients admitted to our neurosurgery service between October 1, 2018 and May 1, 2019. Complications were prospectively recorded and classified as surgical or medical. Univariate and multivariate logistic regressions were used to analyze these data. RESULTS: Eighty-five surgical complications (6.6%) and 110 medical complications (8.6%) resulted from 1285 operations on 1145 patients. Later SST was predictive of complications in the emergent population (odds ratio [OR], 2.28; 95% confidence interval [CI], 1.01-5.15; P = 0.048) but not in the elective population. Extubation in the neurosurgical intensive care unit (NICU) versus the operating room strongly predicted medical complications (OR, 6.91; 95% CI, 3.33-14.34; P < 0.0001). Patients with a later SST were significantly more likely to be extubated in the NICU (P < 0.0001). CONCLUSIONS: Patients undergoing emergent operations with a later SST were significantly more likely to have a postoperative complication. Patients who were extubated in the NICU versus the operating room were significantly more likely to have a medical complication. Patients were more likely to be extubated in the NICU if they had a later SST; therefore, SST may indirectly be associated with an increase in medical complications.

Predictive Factors, 30-Day Clinical Outcomes, and Costs Associated with Cerebrospinal Fluid Leak in Pituitary Adenoma Resection.

Cerebrospinal fluid (CSF) leak is a complication of endoscopic endonasal pituitary adenoma resection. Previous studies examining complications of pituitary adenoma resection have not examined associations of an exhaustive list of clinical and financial variables with CSF leak. We designed a retrospective analysis of 334 consecutive patients that underwent endoscopic endonasal pituitary adenoma resection at a single institution over 5 years, analyzing associations between CSF leak and demographic data, operative data, comorbidities, clinical complications and outcomes, costs, charges, and payments. Of the 20 preoperative variables studied, none were positively associated with CSF leak in between-groups comparison, although multivariate analysis revealed an association with a history of radiation to the skull base (odds ratio [OR], 8.67; 95% confidence interval [CI], 0.94-57.03; p < 0.05). CSF leak was associated with a significantly higher rate of postoperative diabetes insipidus (Δ = 33.4%, p = 0.040) and increased length of stay after operation in between-groups comparison. Multivariate analysis on postoperative variables revealed significant associations between CSF leak and intracerebral hemorrhage (OR, 17.44; 95% CI, 0.65-275.3; p < 0.05) and postoperative intracranial infection (OR, 28.73; 95% CI, 2.04-438.7; p < 0.05). Also, CSF leak was associated with significantly higher costs (Δ = $15,643, p < 0.05) and hospital charges (Δ = $46,026, p < 0.05). Operating room time, room and board, and supplies and implants were the strongest cost drivers. This study highlights the difficulty of utilizing preoperative variables to predict CSF leak, the clinical complications and outcomes of leak, and the financial subcategories that drive the costs, charges, and payments associated with this complication.

Pituitary Dysfunction after Radiation for Anterior Skull Base Malignancies: Incidence and Screening.

Background Management of anterior cranial base malignancies requires multidisciplinary care. Radiation therapy remains a mainstay of definitive or adjuvant treatment. Apart from primary hypothyroidism, the effects of radiation on the hypothalamic-pituitary axis after high-dose treatment of head and neck malignancies remain poorly described. We describe a comprehensive screening protocol for surveillance and characterize the incidence of pituitary dysfunction after radiation for anterior cranial base malignancies. Methods A review of patients prospectively enrolled in a skull base registry at an academic center was performed. Included patients had a history of anterior skull base malignancy and external beam radiation to the primary site, with comprehensive post-treatment pituitary serologies and at least 1 year of post-radiation follow-up. Routine hormonal screening was initiated during the study period for all patients with anterior skull base irradiation. Results Eighty-one patients met inclusion. Fifty-eight patients (71%) demonstrated some laboratory abnormality. Thirty patients (37%) demonstrated evidence of hypopituitarism. Twenty-four (29%) demonstrated central hypogonadism, and 16% of patients showed central hypothyroidism. Ten patients (12%) displayed central adrenal insufficiency with six patients demonstrating panhypopituitarism. Primary tumor location and maximum dose of radiation to the gland appeared to correlate with incidence of hypopituitarism. Conclusion Radiation for malignancies of the anterior skull base resulted in a 37% incidence of hypopituitarism in our study. Given the potential morbidity of hypopituitarism, we recommend annual post-treatment screening in these patients. We describe a comprehensive set of serologies that can be utilized, and recommend updating clinical guidelines to reflect the necessity of this screening.

Near real-time intraoperative brain tumor diagnosis using stimulated Raman histology and deep neural networks.

Intraoperative diagnosis is essential for providing safe and effective care during cancer surgery1. The existing workflow for intraoperative diagnosis based on hematoxylin and eosin staining of processed tissue is time, resource and labor intensive2,3. Moreover, interpretation of intraoperative histologic images is dependent on a contracting, unevenly distributed, pathology workforce4. In the present study, we report a parallel workflow that combines stimulated Raman histology (SRH)5-7, a label-free optical imaging method and deep convolutional neural networks (CNNs) to predict diagnosis at the bedside in near real-time in an automated fashion. Specifically, our CNNs, trained on over 2.5 million SRH images, predict brain tumor diagnosis in the operating room in under 150 s, an order of magnitude faster than conventional techniques (for example, 20-30 min)2. In a multicenter, prospective clinical trial (n = 278), we demonstrated that CNN-based diagnosis of SRH images was noninferior to pathologist-based interpretation of conventional histologic images (overall accuracy, 94.6% versus 93.9%). Our CNNs learned a hierarchy of recognizable histologic feature representations to classify the major histopathologic classes of brain tumors. In addition, we implemented a semantic segmentation method to identify tumor-infiltrated diagnostic regions within SRH images. These results demonstrate how intraoperative cancer diagnosis can be streamlined, creating a complementary pathway for tissue diagnosis that is independent of a traditional pathology laboratory.

Heparin-Induced Pituitary Apoplexy Presenting as Isolated Unilateral Oculomotor Nerve Palsy: A Case Report and Literature Review.

INTRODUCTION: Pituitary apoplexy (PA) is a rare and potentially life-threatening clinical syndrome resulting from pituitary gland hemorrhage and/or infarction. Anticoagulation is a risk factor for triggering PA. Isolated oculomotor nerve palsy is an atypical presentation of PA. CASE PRESENTATION: A 65-year-old African American female with no past medical history of pituitary disease presented to the emergency department (ED) with nonspecific abdominal pain that was thought to be secondary to fecal stasis and subsequently improved with laxatives. She also reported atypical chest pain that was concerning for unstable angina. She was started on aspirin, clopidogrel, and intravenous (IV) heparin. Later, coronary catheterization showed no significant coronary artery disease (CAD). Twelve hours after the procedure, the patient developed acute complete left oculomotor nerve palsy with a severe headache. Magnetic resonance imaging (MRI) of the head showed a large pituitary mass. Pituitary apoplexy was suspected and the patient eventually underwent a successful trans-sphenoidal pituitary resection. DISCUSSION: We report a case of PA manifesting as isolated left oculomotor nerve palsy without visual field defects in the setting of using dual antiplatelet therapy (DAPT) and IV heparin for acute coronary syndrome. To the best of our knowledge, this unique combination has not been previously reported.

Transnasal and Transoral Approaches to Atlantoaxial Synovial Cysts: Report of 3 Cases and Review of the Literature.

BACKGROUND: Synovial cysts are cystic masses lined with pseudostratified columnar cells and containing clear or xanthochromic fluid. Although they are commonly encountered in the lumbar spine, synovial cysts infrequently occur in the cervical spine and rarely involve the odontoid process. The causes of synovial cysts of the odontoid process are unknown, but growth of synovial rests, proliferation of multipotent mesenchymal cells, atlantoaxial instability, and trauma are thought to play a role. CASE DESCRIPTION: We present 3 cases of atlantoaxial cysts with the associated radiographic features, surgical management, and clinical outcomes. No patient had rheumatoid arthritis. In all cases, preoperative differential diagnosis included neoplastic pathologic changes. Two patients underwent odontoidectomy through either an endonasal or a transoral approach, followed by posterior occipitocervical fusion. The third patient underwent an endoscopic transsphenoidal approach for cyst decompression. CONCLUSIONS: Tissue diagnosis is important in confirming pathologic analysis because synovial cysts have radiographic characteristics similar to those of a wide variety of neoplasms of the craniovertebral junction.

A machine learning approach to predict early outcomes after pituitary adenoma surgery.

OBJECTIVEPituitary adenomas occur in a heterogeneous patient population with diverse perioperative risk factors, endocrinopathies, and other tumor-related comorbidities. This heterogeneity makes predicting postoperative outcomes challenging when using traditional scoring systems. Modern machine learning algorithms can automatically identify the most predictive risk factors and learn complex risk-factor interactions using training data to build a robust predictive model that can generalize to new patient cohorts. The authors sought to build a predictive model using supervised machine learning to accurately predict early outcomes of pituitary adenoma surgery.METHODSA retrospective cohort of 400 consecutive pituitary adenoma patients was used. Patient variables/predictive features were limited to common patient characteristics to improve model implementation. Univariate and multivariate odds ratio analysis was performed to identify individual risk factors for common postoperative complications and to compare risk factors with model predictors. The study population was split into 300 training/validation patients and 100 testing patients to train and evaluate four machine learning models using binary classification accuracy for predicting early outcomes.RESULTSThe study included a total of 400 patients. The mean ± SD patient age was 53.9 ± 16.3 years, 59.8% of patients had nonfunctioning adenomas and 84.7% had macroadenomas, and the mean body mass index (BMI) was 32.6 ± 7.8 (58.0% obesity rate). Multivariate odds ratio analysis demonstrated that age < 40 years was associated with a 2.86 greater odds of postoperative diabetes insipidus and that nonobese patients (BMI < 30) were 2.2 times more likely to develop postoperative hyponatremia. Using broad criteria for a poor early postoperative outcome-major medical and early surgical complications, extended length of stay, emergency department admission, inpatient readmission, and death-31.0% of patients met criteria for a poor early outcome. After model training, a logistic regression model with elastic net (LR-EN) regularization best predicted early postoperative outcomes of pituitary adenoma surgery on the 100-patient testing set-sensitivity 68.0%, specificity 93.3%, overall accuracy 87.0%. The receiver operating characteristic and precision-recall curves for the LR-EN model had areas under the curve of 82.7 and 69.5, respectively. The most important predictive variables were lowest perioperative sodium, age, BMI, highest perioperative sodium, and Cushing's disease.CONCLUSIONSEarly postoperative outcomes of pituitary adenoma surgery can be predicted with 87% accuracy using a machine learning approach. These results provide insight into how predictive modeling using machine learning can be used to improve the perioperative management of pituitary adenoma patients.

Surgical Treatment of Olfactory Neuroblastoma: Major Complication Rates, Progression Free and Overall Survival.

Objective We aimed to compare major complication rates in patients undergoing open versus endoscopic resection of olfactory neuroblastoma (ONB) and to determine the prognostic utility of the Kadish staging and Hyams grading systems with respect to progression-free survival (PFS) and overall survival (OS). Methods It is a retrospective review of experience in treating ONB at a single tertiary care hospital from 1987 through 2015. Major complications were defined as cerebrospinal fluid (CSF) leak, meningitis, osteomyelitis, tracheostomy, and severe neurologic injury. Results Forty-one patients were included. An open approach was used in 34 (83%), endoscopic in 6 (15%), and combined in 1 (2%) case. Rates of major complications by surgical approach were 17% after endoscopic versus 31% after open ( p = 0.65). There was no significant difference in PFS or OS based on Kadish B versus C (PFS, p = 0.28; OS, p = 0.11) or Hyams grade 1 and 2 versus Hyams grade 3 and 4 (PFS, p = 0.53; OS, p = 0.38). Conclusions There was no significant difference in major complications between open and endoscopic approaches for the treatment of ONB. Patient stratification using the Kadish staging and Hyams grading systems did not show significant differences in PFS or OS. Further research is needed to determine if a different staging system would better predict patient outcomes.

Korsakoff syndrome from retrochiasmatic suprasellar lesions: rapid reversal after relief of cerebral compression in 4 cases.

Korsakoff syndrome is a chronic memory disorder caused by a severe deficiency of thiamine that is most commonly observed in alcoholics. However, some have proposed that focal structural lesions disrupting memory circuits-in particular, the mammillary bodies, the mammillothalamic tract, and the anterior thalamus-can give rise to this amnestic syndrome. Here, the authors present 4 patients with reversible Korsakoff syndromes caused by suprasellar retrochiasmatic lesions compressing the mammillary bodies and adjacent caudal hypothalamic structures. Three of the patients were found to have large pituitary macroadenomas in their workup for memory deficiency and cognitive decline with minimal visual symptoms. These tumors extended superiorly into the suprasellar region in a retrochiasmatic position and caused significant mass effect in the bilateral mammillary bodies in the base of the brain. These 3 patients had complete and rapid resolution of amnestic problems shortly after initiation of treatment, consisting of resection in 1 case of nonfunctioning pituitary adenoma or cabergoline therapy in 2 cases of prolactinoma. The fourth patient presented with bizarre and hostile behavior along with significant memory deficits and was found to have a large cystic craniopharyngioma filling the third ventricle and compressing the midline diencephalic structures. This patient underwent cyst fenestration and tumor debulking, with a rapid improvement in his mental status. The rapid and dramatic memory improvement observed in all of these cases is probably due to a reduction in the pressure imposed by the lesions on structures contiguous to the third ventricle, rather than a direct destructive effect of the tumor, and highlights the essential role of the caudal diencephalic structures-mainly the mammillary bodies-in memory function. In summary, large pituitary lesions with suprasellar retrochiasmatic extension and third ventricular craniopharyngiomas can cause severe Korsakoff-like amnestic syndromes, probably because of bilateral pressure on or damage to mammillary bodies, anterior thalamic nuclei, or their major connections. Neuropsychiatric symptoms may rapidly and completely reverse shortly after initiation of therapy via surgical decompression of tumors or pharmacological treatment of prolactinomas. Early identification of these lesions with timely treatment can lead to a favorable prognosis for this severe neuropsychiatric disorder.

Ventriculoscopic Surgery for Cystic Retrochiasmatic Craniopharyngiomas: Indications, Surgical Technique, and Short-Term Patient Outcomes.

BACKGROUND: Attempted gross-total resection for the management of cystic retrochiasmatic craniopharyngiomas can cause severe hypothalamic dysfunction and decrease overall survival. Ventriculoscopic surgery is a minimally invasive alternative; however, potential indications and technique have not been well defined. OBJECTIVE: To present our indications and technique for the ventriculoscopic treatment of cystic retrochiasmatic craniopharyngiomas. METHODS: We evaluated all patients with retrochiasmatic craniopharyngiomas for ventriculoscopic surgery. Indications and operative technique were developed to minimize operative morbidity, relieve mass effect, and optimize functional outcome. Cyst size and functional outcomes were statistically evaluated to determine radiographic and short-term clinical outcome. RESULTS: Indications for ventriculoscopic surgery included (1) radiographic evidence of hypothalamic involvement and (2) major cystic component. Ten patients met indications, and mean follow-up was 2.5 ± 1.6 yr. The surgical technique included wide cyst fenestration at the foramen of Monro, and fenestration of inferior cyst wall/third ventriculostomy ("through-and-through" technique). Preoperative Karnofsky performance status was 70 ± 15 and was inversely correlated with preoperative cyst size (13 ± 13 cm3). A statistically significant reduction in cyst size was found on early postoperative imaging (2.1 ± 4.3 cm3). Seven patients received postoperative radiotherapy. Postoperative performance scores (81 ± 8.3) had improved; no patient suffered functional decline. Pre- and postoperative body mass indices were similar. No patient had short-term hypothalamic obesity. CONCLUSION: Ventriculoscopic surgery, with or without adjuvant treatments, can reduce early postoperative tumor volume and improve short-term functional status in cystic retrochiasmatic craniopharyngiomas with hypothalamic involvement; it should be considered a minimally invasive option in the multimodal treatment of craniopharyngiomas. Further studies are needed to determine long-term efficacy.

Pathogenetic Analysis of Sinonasal Teratocarcinosarcomas Reveal Actionable ß-catenin Overexpression and a ß-catenin Mutation.

Objective Sinonasal teratocarcinosarcomas are rare, aggressive tumors of the skull base. Treatment options are limited and outcomes are poor. Little is known in regard to the genetic factors regulating these tumors. Characterization of actionable molecular alterations in these tumors could provide potentially successful therapeutic options. Methods We performed targeted exome sequencing on an index sinonasal teratocarcinosarcoma specimen to identify potential driver mutations. We performed immunohistochemical stains for ß-catenin on paraffin-embedded tissue on the index tumor and a subsequent teratocarcinosarcoma. Online databases of cancer mutations (Catalogue of Somatic Mutations in Cancer and The Cancer Genome Atlas) were accessed. Results We identified an activating p.S45F mutation in ß-catenin in our index sinonasal teratocarcinosarcoma. This mutation results in constitutive signaling in the Wnt/ß-catenin pathway. We confirmed ß-catenin overexpression and nuclear localization via immunohistochemistry in the index tumor and a second patient. The p.S45F activating mutation was found in a variety of solid tumors, and accounts for 3.3 to 10.4% of all known ß-catenin mutations. Conclusion We identified a potential driver mutation in ß-catenin in a sinonasal teratocarcinosarcoma, resulting in ß-catenin overexpression. These findings suggest a role for the Wnt/ß-catenin pathway in sinonasal teratocarcinosarcoma tumorigenesis and a role for anti-ß-catenin targeted therapy.

Frontal Sinus Breach During Routine Frontal Craniotomy Significantly Increases Risk of Surgical Site Infection: 10-Year Retrospective Analysis.

BACKGROUND: Frontotemporal craniotomies are commonly performed for a variety of neurosurgical pathologies. Infections related to craniotomies cause significant morbidity. We hypothesized that the risk of cranial surgical site infections (SSIs) may be increased in patients whose frontal sinuses are breached during craniotomy. OBJECTIVE: To compare the rate of cranial SSIs in patients undergoing frontotemporal craniotomies with and without frontal sinus breach (FSB). METHODS: We performed a retrospective analysis of all patients undergoing frontotemporal craniotomies for the management of cerebral aneurysms from 2005 to 2014. This study included 862 patients undergoing 910 craniotomies. Primary outcome of interest was occurrence of a cranial SSI. Standard statistical methods were utilized to explore associations between a variety of variables including FSB, cranial SSI, and infections requiring reoperation. RESULTS: Of the 910 craniotomies, 141 (15.5%) involved FSB. Of those involving FSB, 22 (15.6%) developed a cranial SSI, compared to only 56 of the 769 without FSB (7.3%; P = .001). Cranial SSI requiring reoperation was much more likely in patients with FSB compared to those without a breach (7.8% vs 1.6%; P < .001). In those presenting with cranial SSIs, epidural abscess formation was more common with FSB compared to no FSB (27.3% vs 5.4%; P = .006). In multivariate analysis, breach of the frontal sinus was significantly associated with cranial SSI (OR 2.16; 95% CI 1.24-3.78; P = .01) and reoperation (OR 4.20; 95% CI 1.66-10.65; P = .003). CONCLUSION: Patients undergoing frontotemporal craniotomies are at significantly greater risk of serious cranial SSIs if the frontal sinus has been breached.

STAT3 Inhibition as a Therapeutic Strategy for Chordoma.

Objective Signal transducer and activator of transcription (STAT) proteins regulate key cellular fate decisions including proliferation and apoptosis. STAT3 overexpression induces tumor growth in multiple neoplasms. STAT3 is constitutively activated in chordoma, a tumor with a high recurrence rate despite maximal surgical and radiation treatment. We hypothesized that a novel small molecule inhibitor of STAT3 (FLLL32) would induce significant cytotoxicity in sacral and clival chordoma cells. Methods Sacral (UCh1) and clival (UM-CHOR-1) chordoma cell lines were grown in culture (the latter derived from primary tumor explants). FLLL32 dosing parameters were optimized using cell viability assays. Antitumor potential of FLLL32 was assessed using clonal proliferation assays. Potential mechanisms underlying observed cytotoxicity were examined using immunofluorescence assays. Results FLLL32 induced significant cytotoxicity in UCh1 and UM-CHOR-1 chordoma cells, essentially eliminating all viable cells, correlating with observed downregulation in activated, phosphorylated STAT3 upon administration of FLLL32. Mechanisms underlying the observed cytotoxicity included increased apoptosis and reduced cellular proliferation through inhibition of mitosis. Conclusion As a monotherapy, FLLL32 induces potent tumor kill in vitro in chordoma cell lines derived from skull base and sacrum. This effect is mediated through inhibition of STAT3 phosphorylation, increased susceptibility to apoptosis, and suppression of cell proliferation.

Comparison of the accuracy and proximal shunt failure rate of freehand placement versus intraoperative guidance in parietooccipital ventricular catheter placement.

OBJECTIVE The aim of this paper is to compare the accuracy of the freehand technique versus the use of intraoperative guidance (either ultrasound guidance or frameless stereotaxy) for placement of parietooccipital ventricular catheters and to determine factors associated with reduced proximal shunt failure. METHODS This retrospective cohort study included all patients from 2 institutions who underwent a ventricular cerebrospinal fluid (CSF) shunting procedure in which a new parietooccipital ventricular catheter was placed between January 2005 and December 2013. Data abstracted for each patient included age, sex, method of ventricular catheter placement, side of ventricular catheter placement, Evans ratio, and bifrontal ventricular span. Postoperative radiographic studies were reviewed for accuracy of ventricular catheter placement. Medical records were also reviewed for evidence of shunt failure requiring revision. Standard statistical methods were used for analysis. RESULTS A total of 257 patients were included in the study: 134 from the University of Michigan and 123 from Washington University in St. Louis. Accurate ventricular catheter placement was achieved in 81.2% of cases in which intraoperative guidance was used versus 67.3% when the freehand technique was used. Increasing age reduced the likelihood of accurate catheter placement (OR 0.983, 95% CI 0.971-0.995; p = 0.005), while the use of intraoperative guidance significantly increased the likelihood (OR 2.809, 95% CI 1.406-5.618; p = 0.016). During the study period, 108 patients (42.0%) experienced shunt failure, 79 patients (30.7%) had failure involving the proximal catheter, and 53 patients (20.6%) had distal failure (valve or distal catheter). Increasing age reduced the likelihood of being free from proximal shunt failure (OR 0.983, 95% CI 0.970-0.995; p = 0.008), while both the use of intraoperative guidance (OR 2.385, 95% CI 1.227-5.032; p = 0.011), and accurate ventricular catheter placement (OR 3.424, 95% CI 1.796-6.524; p = 0.009) increased the likelihood. CONCLUSIONS The use of intraoperative guidance during parietooccipital ventricular catheter placement as part of a CSF shunt system significantly increases the likelihood of accurate catheter placement and subsequently reduces the rate of proximal shunt failure.

"Micromegaly": an update on the prevalence of acromegaly with apparently normal GH secretion in the modern era.

PURPOSE: Approximately 25 % of cases of clinically active acromegaly cases treated in our academic center between 1996 and 2000, were diagnosed in patients who had elevated plasma IGF-1 levels, but apparently "normal" 24-h mean plasma GH levels. The current study served to update the data for patients with acromegaly referred to our facility, after increasing awareness of this "normal" GH subpopulation throughout the medical community. METHODS: A retrospective chart review was conducted on 157 patients with acromegaly who underwent resection of a confirmed somatotroph pituitary adenoma at the University of Michigan Health System between the dates of 1 Jan 2001 to 23 Sept 2015. RESULTS: Overall prevalence of acromegalic patients with "normal" GH levels, defined as GH <4.7 ng/mL, was 31 %. Over time, the percentage of patients with "normal" GH at diagnosis did not decline: 26 % from 2001 to 2005, 19 % from 2006 to 2010, and 47 % from 2011 to 2015. Mean pituitary tumor size was 1.8 ± 0.1 cm for the group with elevated GH, and 1.2 ± 0.1 cm for the group with "normal" GH (p < 0.001). Percent microadenomas was higher in a group with "normal" GH as compared to those with elevated GH (48 vs. 12 %, p < 0.001), and tumors >2 cm in the maximal diameter were encountered more frequently in the group with elevated GH (43 vs. 14 %, p < 0.001). CONCLUSIONS: Our data show that a substantial percentage of patients with clinical acromegaly have "normal" GH, and therefore strengthens the growing body of evidence which supports the leading role of IGF-1 levels in diagnostic evaluation. At the present time, questions about the natural course of "micromegaly" and treatment benefits compared to the subpopulation with elevated GH levels remain unanswered, but research continues to build on our understanding of the heterogeneous population of individuals.