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Background and Objectives: To address the lack of a multicenter pituitary surgery research consortium in the United States, we established the Registry of Adenomas of the Pituitary and Related Disorders (RAPID). The goals of RAPID are to examine surgical outcomes, improve patient care, disseminate best practices, and facilitate multicenter surgery research at scale. Our initial focus is Cushing disease (CD). This study aims to describe the current RAPID patient cohort, explore surgical outcomes, and lay the foundation for future studies addressing the limitations of previous studies., Methods: Prospectively and retrospectively obtained data from participating sites were aggregated using a cloud-based registry and analyzed retrospectively. Standard preoperative variables and outcome measures included length of stay, unplanned readmission, and remission., Results: By July 2023, 528 patients with CD had been treated by 26 neurosurgeons with varying levels of experience at 9 academic pituitary centers. No surgeon treated more than 81 of 528 (15.3%) patients. The mean ± SD patient age was 43.8 ± 13.9 years, and most patients were female (82.2%, 433/527). The mean tumor diameter was 0.8 ± 2.7 cm. Most patients (76.6%, 354/462) had no prior treatment. The most common pathology was corticotroph tumor (76.8%, 381/496). The mean length of stay was 3.8 ± 2.5 days. The most common discharge destination was home (97.2%, 513/528). Two patients (0.4%, 2/528) died perioperatively. A total of 57 patients (11.0%, 57/519) required an unplanned hospital readmission within 90 days of surgery. The median actuarial disease-free survival after index surgery was 8.5 years., Conclusion: This study examined an evolving multicenter collaboration on patient outcomes after surgery for CD. Our results provide novel insights on surgical outcomes not possible in prior single-center studies or with national administrative data sets. This collaboration will power future studies to better advance the standard of care for patients with CD., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

No comprehensive classification system that guides prognosis and therapy of pituitary adenomas exists. The 2022 WHO histopathology-based classification system can only be applied to lesions that are resected, which represent few clinically significant pituitary adenomas. Many factors independent of histopathology provide mechanistic insight into causation and influence prognosis and treatment of pituitary adenomas. We propose a new approach to guide prognosis and therapy of pituitary adenomas by integrating clinical, genetic, biochemical, radiological, pathological, and molecular information for all adenomas arising from anterior pituitary cell lineages. The system uses an evidence-based scoring of risk factors to yield a cumulative score that reflects disease severity and can be used at the bedside to guide pituitary adenoma management. Once validated in prospective studies, this simple manageable classification system could provide a standardised platform for assessing disease severity, prognosis, and effects of therapy on pituitary adenomas., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Context: Pituitary apoplexy (PA) has been traditionally considered a neurosurgical emergency, yet retrospective single-institution studies suggest similar outcomes among patients managed medically., Objective: We established a multicenter, international prospective registry to compare presentation and outcomes in PA patients treated with surgery or medical management alone., Methods: A centralized database captured demographics, comorbidities, clinical presentation, visual findings, hormonal status, and imaging features at admission. Treatment was determined independently by each site. Key outcomes included visual, oculomotor, and hormonal recovery, complications, and hospital length of stay. Outcomes were also compared based on time from symptom onset to surgery, and from admission or transfer to the treating center. Statistical testing compared treatment groups based on 2-sided hypotheses and P less than .05., Results: A total of 100 consecutive PA patients from 12 hospitals were enrolled, and 97 (67 surgical and 30 medical) were evaluable. Demographics, clinical features, presenting symptoms, hormonal deficits, and imaging findings were similar between groups. Severe temporal visual field deficit was more common in surgical patients. At 3 and 6 months, hormonal, visual, and oculomotor outcomes were similar. Stratifying based on severity of visual fields demonstrated no difference in any outcome at 3 months. Timing of surgery did not affect outcomes., Conclusion: We found that medical and surgical management of PA yield similar 3-month outcomes. Although patients undergoing surgery had more severe visual field deficits, we could not clearly demonstrate that surgery led to better outcomes. Even without surgery, apoplectic tumor volumes regress substantially within 2 to 3 months, indicating that surgery is not always needed to reduce mass effect., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Cushing's disease (CD) is a serious endocrine disorder attributed to an adrenocorticotropic hormone (ACTH)-secreting pituitary neuroendocrine tumor (PitNET) that that subsequently leads to chronic hypercortisolemia. PitNET regression has been reported following treatment with the investigational selective glucocorticoid receptor (GR) modulator relacorilant, but the mechanisms behind that effect remain unknown. Human PitNET organoid models were generated from induced human pluripotent stem cells (iPSCs) or fresh tissue obtained from CD patient PitNETs (hPITOs). Genetically engineered iPSC derived organoids were used to model the development of corticotroph PitNETs expressing USP48 (iPSC USP48 ) or USP8 (iPSC USP8 ) somatic mutations. Organoids were treated with the GR antagonist mifepristone or the GR modulator relacorilant with or without somatostatin receptor (SSTR) agonists pasireotide or octreotide. In iPSC USP48 and iPSC USP8 cultures, mifepristone induced a predominant expression of SSTR2 with a concomitant increase in ACTH secretion and tumor cell proliferation. Relacorilant predominantly induced SSTR5 expression and tumor cell apoptosis with minimal ACTH induction. Hedgehog signaling mediated the induction of SSTR2 and SSTR5 in response to mifepristone and relacorilant. Relacorilant sensitized PitNET organoid responsiveness to pasireotide. Therefore, our study identified the potential therapeutic use of relacorilant in combination with somatostatin analogs and demonstrated the advantages of relacorilant over mifepristone, supporting its further development for use in the treatment of Cushing's disease patients., Competing Interests: Conflicts of Interest All authors have read the journal's policy on disclosure of potential conflicts of interest.. Dr. Andreas G. Moraitis and Dr. Andrew E.Greenstein are employees and stock holders of Corcept. Dr. Kevin CJ Yuen has received research grants to the Barrow Neurological Institute from Crinetics, Ascendis, Corcept, and Amryt. Dr. Yuen has served as an advisory board member for Novo Nordisk, Ipsen, Amryt, Crinetics, Recordati and Xeris, and served as a speaker for Recordati, Novo Nordisk and Corcept. All other authors have no potential conflicts of interest to declare., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

(1) Background: Cushing's disease (CD) is a serious endocrine disorder caused by an adrenocorticotropic hormone (ACTH)-secreting pituitary neuroendocrine tumor (PitNET) that stimulates the adrenal glands to overproduce cortisol. Chronic exposure to excess cortisol has detrimental effects on health, including increased stroke rates, diabetes, obesity, cognitive impairment, anxiety, depression, and death. The first-line treatment for CD is pituitary surgery. Current surgical remission rates reported in only 56% of patients depending on several criteria. The lack of specificity, poor tolerability, and low efficacy of the subsequent second-line medical therapies make CD a medical therapeutic challenge. One major limitation that hinders the development of specific medical therapies is the lack of relevant human model systems that recapitulate the cellular composition of PitNET microenvironment. (2) Methods: human pituitary tumor tissue was harvested during transsphenoidal surgery from CD patients to generate organoids (hPITOs). (3) Results: hPITOs generated from corticotroph, lactotroph, gonadotroph, and somatotroph tumors exhibited morphological diversity among the organoid lines between individual patients and amongst subtypes. The similarity in cell lineages between the organoid line and the patient's tumor was validated by comparing the neuropathology report to the expression pattern of PitNET specific markers, using spectral flow cytometry and exome sequencing. A high-throughput drug screen demonstrated patient-specific drug responses of hPITOs amongst each tumor subtype. Generation of induced pluripotent stem cells (iPSCs) from a CD patient carrying germline mutation CDH23 exhibited dysregulated cell lineage commitment. (4) Conclusions: The human pituitary neuroendocrine tumor organoids represent a novel approach in how we model complex pathologies in CD patients, which will enable effective personalized medicine for these patients.

Purpose: This study evaluates the temporal evolution of the spatial relationship between the pituitary adenoma transsphenoidal surgical cavity and the adjacent optic chiasm and discusses implications on timing and choice of radiotherapy modality., Methods: This retrospective observational review analyzed factors that might influence the postoperative relationship between the surgical cavity and the optic chiasm, including tumor type, craniocaudal tumor and resection cavity dimensions, the preoperative distance between tumor and the optic chiasm, the presence of cavernous sinus invasion, and the choice of intraoperative packing material. Changes observed on magnetic resonance imaging in the preoperative, immediate (within 72 h), and delayed (≥3 months) postoperative periods were compared., Results: Sixty-five patient histories were analyzed. Preoperatively, the pituitary adenoma was apposed to the optic chiasm in 43 patients (66%). Postoperatively, 34 patients (52%) in the immediate postoperative period and 54 patients (83%) in the delayed postoperative period had a distance ≥2 mm between the resection cavity and the optic chiasm. This distance provides a greater margin of safety with adjuvant radiosurgery. Preoperative tumor size showed a strong association with postoperative descent of the optic chiasm., Conclusions: Preoperative tumor size and degree of mass effect on the optic chiasm predict postoperative changes. In this study, the distance between the resection cavity and the optic chiasm was greater at ≥3 months postoperatively than in the immediate postoperative period, regardless of preoperative mass effect, indicating radiotherapy planning should be deferred to ≥3 months postoperatively when not precluded by aggressive histological characteristics that necessitate more immediate treatment., Precis: To investigate the temporal relationship between the postoperative sellar surgical cavity and the adjacent optic apparatus after transsphenoidal resection of pituitary adenomas and the implications for radiotherapy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives/hypothesis: Sinonasal Outcomes Test-22 (SNOT-22) is used widely as a patient-reported sinonasal quality-of-life (QOL) instrument for endoscopic endonasal pituitary surgery. However, it has never been validated in this population. This study explores the psychometric validity of SNOT-22 to determine if it is a valid scale in patients undergoing endoscopic pituitary surgery., Study Design: Multicenter prospective trial., Methods: Adult patients (n = 113) with pituitary tumors undergoing endoscopic surgery were enrolled in a multicenter study. Patient-reported QOL was assessed using SNOT-22 and the Anterior Skull Base Nasal Inventory-12. Face validity, internal consistency, responsiveness to clinical change, test-retest reliability, and concurrent validity were determined using standard statistical methods., Results: Internal consistency using Cronbach's alpha at baseline and 2 weeks postoperatively were 0.911 and 0.922, indicating SNOT-22 performed well as a single construct. Mean QOL scores were significantly worse at 2 weeks than baseline (16.4 ± 15.1 vs. 23.1 ± 16.4, P < .001), indicating the scale is responsive to clinical change. However, only 11/22 items demonstrated significant changes in mean scores at 2 weeks. Correlation between scores at 2 and 3 weeks was high, suggesting good test-retest reliability, r(107) = 0.75, P < .001. Factor analysis suggests the five-factor solution proposed for the SNOT-22 in rhinosinusitis patients is not valid in pituitary surgery patients., Conclusions: The SNOT-22 is a valid QOL instrument in patients undergoing endoscopic pituitary surgery. However, because it includes 22 items, can be applied only as a single construct, 50% of the items do not demonstrate changes after surgery, and is not as sensitive to change as other scales, shorter instruments developed specifically for this patient population may be preferable., Level of Evidence: 2 Laryngoscope, 131:E2757-E2763, 2021., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Postoperative prophylactic antibiotics are commonly used in pituitary surgery, but evidence supporting their use is lacking, which has implications for antibiotic stewardship., Objective: To evaluate whether receipt of postoperative oral antibiotics results in superior sinonasal quality of life (QOL) compared with placebo among patients who undergo endoscopic endonasal transsphenoidal pituitary surgery., Methods: Patients were randomized to receive either oral placebo or cefdinir (trimethoprim-sulfamethoxazole in patients intolerant to cefdinir) for 7 d after surgery. They were monitored for 12 wk. The primary outcome measure was sinonasal QOL at 2 wk on the Anterior Skull Base Nasal Inventory-12. Supplementary end points included sinonasal QOL reported on the Sinonasal Outcome Test-22 and objective endoscopy scores to assess nasal healing according to the Lund-Kennedy method., Results: A total of 461 patients were screened, 131 were randomized, and 113 (placebo arm: 55; antibiotic arm: 58) were analyzed. There was no clinically meaningful or statistically significant difference in sinonasal QOL at any measured time point (P ≥ .24) using either instrument. Nasal cavity endoscopy scores were not significantly different at 1 to 2 wk after surgery (P = .25) or at 3 to 4 wk after surgery (P = .08)., Conclusion: Postoperative prophylactic oral antibiotics did not result in superior sinonasal QOL compared with placebo among patients who underwent standard endoscopic transsphenoidal surgery., (© Congress of Neurological Surgeons 2021.)

Objective: Current practice guidelines recommend delayed (≥ 3 months after operation) postoperative MRI after transsphenoidal surgery for pituitary adenomas, although this practice defers obtaining important information, such as the presence of a residual adenoma, that might influence patient management during the perioperative period. In this study, the authors compared detection of residual adenomas by means of early postoperative (EPO) MRI (< 48 hours postsurgery) with both surgeon intraoperative assessment and late postoperative (LPO) MRI at 3 months., Methods: Adult patients who underwent microscopic transsphenoidal surgery for pituitary adenomas with MRI preoperatively, < 48 hours after the operation, 3 months postoperatively, and yearly for 4 years were included. The presence or absence of residual tumor was assessed intraoperatively by a single surgeon and postoperatively by 2 neuroradiologists blinded to the intraoperative assessment and other postoperative imaging studies. The presence of residual tumor was confirmed by reresection, tumor growth on imaging, or hormonal evidence. Interreader reliability was calculated at each imaging time point. Specificity, sensitivity, positive predictive value, and negative predictive value for EPO and LPO imaging and intraoperative assessment were determined., Results: In total, 102 consecutive patients who underwent microscopic transsphenoidal resection of a pituitary adenoma were included. Eighteen patients (18%) had confirmed residual tumors (12 confirmed by tumor growth, 5 by surgery, and 1 by biochemical evidence of persistent disease). Interreader reliability for detecting residual tumor on EPO MRI was almost perfect (κ = 0.88) and significantly higher than that for LPO MRI (κ = 0.69, p = 0.03). EPO MRI was highly specific for residual tumor (98%), a finding similar to that for intraoperative assessment (99%, p = 0.60) and significantly higher than that for LPO MRI (81%, p < 0.001). Notably, EPO MRI was significantly more sensitive for residual tumor (100%) than both intraoperative assessment (78%, p = 0.04) and LPO MRI (78%, p = 0.04). EPO MRI had a 100% negative predictive value and was used to find 4 residual tumors that were not identified intraoperatively. Residual tumors found on EPO MRI allowed for reresection during the same hospitalization for 3 patients., Conclusions: EPO MRI after transsphenoidal pituitary surgery can be reliably interpreted and has greater sensitivity for detecting residual tumor than intraoperative assessment and LPO MRI. This result challenges current guidelines stating that delayed postoperative imaging is preferable to early imaging. Pituitary surgeons should consider performing EPO MRI either in addition to or instead of delayed imaging.

Background: The influence of the surgeon's preoperative goal regarding the extent of tumor resection on patient outcomes has not been carefully studied among patients with nonfunctioning pituitary adenomas., Objective: To analyze the relationship between surgical tumor removal goal and patient outcomes in a prospective multicenter study., Methods: Centrally adjudicated extent of tumor resection (gross total resection [GTR] and subtotal resection [STR]) data were analyzed using standard univariate and multivariable analyses., Results: GTR was accomplished in 148 of 171 (86.5%) patients with planned GTR and 32 of 50 (64.0%) patients with planned STR (P = .001). Sensitivity, specificity, positive predictive value, and negative predictive value of GTR goal were 82.2, 43.9, 86.5, and 36.0%, respectively. Knosp grade 0-2, first surgery, and being an experienced surgeon were associated with surgeons choosing GTR as the goal (P < .01). There was no association between surgical goal and presence of pituitary deficiency at 6 mo (P = .31). Tumor Knosp grade (P = .004) and size (P = .001) were stronger predictors of GTR than was surgical goal (P = .014). The most common site of residual tumor was the cavernous sinus (29 of 41 patients; 70.1%)., Conclusion: This is the first pituitary surgery study to examine surgical goal regarding extent of tumor resection and associated patient outcomes. Surgical goal is a poor predictor of actual tumor resection. A more aggressive surgical goal does not correlate with pituitary gland dysfunction. A better understanding of the ability of surgeons to meet their expectations and of the factors associated with surgical result should improve prognostication and preoperative counseling., (Copyright © 2019 by the Congress of Neurological Surgeons.)

Background: A simple, reliable grading scale to better characterize nonfunctioning pituitary adenomas (NFPAs) preoperatively has potential for research and clinical applications., Objective: To develop a grading scale from a prospective multicenter cohort of patients that accurately and reliably predicts the likelihood of gross total resection (GTR) after transsphenoidal NFPA surgery., Methods: Extent-of-resection (EOR) data from a prospective multicenter study in transsphenoidal NFPA surgery were analyzed (TRANSSPHER study; ClinicalTrials.gov NCT02357498). Sixteen preoperative radiographic magnetic resonance imaging (MRI) tumor characteristics (eg, tumor size, invasion measures, tumor signal characteristics, and parameters impacting surgical access) were evaluated to determine EOR predictors, to calculate receiver-operating characteristic curves, and to develop a grading scale. A separate validation cohort (n = 165) was examined to assess the scale's performance and inter-rater reliability., Results: Data for 222 patients from 7 centers treated by 15 surgeons were analyzed. Approximately one-fifth of patients (18.5%; 41 of 222) underwent subtotal resection (STR). Maximum tumor diameter > 40 mm; nodular tumor extension through the diaphragma into the frontal lobe, temporal lobe, posterior fossa, or ventricle; and Knosp grades 3 to 4 were identified as independent STR predictors. A grading scale (TRANSSPHER grade) based on a combination of these 3 features outperformed individual variables in predicting GTR (AUC, 0.732). In a validation cohort, the scale exhibited high sensitivity and specificity (AUC, 0.779) and strong inter-rater reliability (kappa coefficient, 0.617)., Conclusion: This simple, reliable grading scale based on preoperative MRI characteristics can be used to better characterize NFPAs for clinical and research purposes and to predict the likelihood of achieving GTR., (Copyright © 2019 by the Congress of Neurological Surgeons.)

Purpose: The 2017 World Health Organization classification of pituitary tumors redefined pituitary null cell adenomas (NCAs) by restricting this diagnostic category to pituitary tumors that are negative for pituitary transcription factors and adenohypophyseal hormones. The clinical behavior of this redefined entity has not been widely studied, and this is a major shortcoming of the classification. This study evaluated the imaging and clinical features of NCAs from two pituitary centers and compared them with those of gonadotroph adenomas (GAs)., Methods: Imaging, pathologic, and clinical characteristics of NCAs and GAs were retrospectively reviewed. Tumor immunohistochemistry was performed to confirm absence of adenohypophyseal hormones and pituitary transcription factor expression., Results: Thirty-one NCAs were compared with 38 GAs. NCAs were more likely to invade the cavernous sinus (15/31 [48%] vs. 5/38 [13%], P = .003) and had a higher proliferative index (i.e., MIB-1 > 3%, 11/31 [35%] vs. 5/38 [13%], P = .04). Gross total resection was less likely in the NCA group (19/31 [61%] vs. 33/38 [87], P = .02). Progression-free survival was worse in the NCA cohort (5-year progression-free survival, 0.70 vs. 1.00; P = .011, by log-rank test)., Conclusions: Compared with GAs, NCAs are more invasive at the time of presentation and have a more aggressive clinical course. This study provides evidence that NCAs represent a distinct clinicopathologic entity with behavior that differs adversely from that of GAs. This may inform clinical decision-making, including frequency of postoperative tumor surveillance and timing of adjunctive treatments.

Sodium perturbations are a common complication after pituitary surgery, with hyponatremia being the most frequent. Postoperative assessments should be tailored to the early and late periods, and monitoring sodium perturbations is recommended. Cerebral salt wasting is rare after pituitary surgery, and diagnosis and management can be challenging. Providing patient counseling and close postoperative follow-up is important to effectively manage diabetes insipidus and reduce hospital readmissions due to sodium perturbations., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: Granular cell tumors (GCTs), pituicytomas, and spindle cell oncocytomas are rare, nonfunctioning pituitary tumors sharing positive staining of thyroid transcription factor 1. We present our series, the first single-institutional report with long-term surgical follow-up of all 3 tumor types., Methods: Our institutional pathology database was queried for these 3 pathologic diagnoses. Clinical records were assessed for clinical presentation, preoperative and postoperative endocrine status, tumor location on imaging, surgical characteristics, pathology results, and tumor recurrence., Results: Data were analyzed for 4 patients with GCTs, 4 with pituicytomas, and 3 with spindle cell oncocytomas. The most common symptoms at presentation were vision changes (64%), headache (55%), endocrine abnormalities (55%), and fatigue (46%). GCTs were the only subtype to present exclusively in the infundibulum and the only subtype in our series to be treated with a transcranial transsylvian approach to resection (n = 2). In our study, in contrast to other reports, estimated blood loss was less than 300 mL in all patients. Imaging confirmed gross total resection in all 11 cases with no known recurrences at a mean (standard deviation) follow-up of 4.7 (3.7) years., Conclusions: We present a single-institution series of rare thyroid transcription factor 1-staining posterior pituitary tumors of the sellar region. Key novel findings include gross total resection with no tumor recurrence at nearly 5 years of mean follow-up and no cases of excess or uncontrolled blood loss. Our findings reinforce the observation that GCTs present in the suprasellar space., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: Patients who undergo transsphenoidal surgery can experience hormonal, electrolyte, and fluid disturbances in the postoperative period leading to outpatient readmissions for medical management. Our goal was to determine whether use of a wrist-mounted physiologic tracking device is feasible in this setting and whether changes or trends in these parameters after discharge can help predict aberrant physiology in these patients., Methods: Wrist-mounted physiologic tracking devices that transmit data via Bluetooth to a mobile device were used to monitor patients. Preoperative baseline data and postoperative data were aggregated daily to compare within-patient and between-patient trends., Results: Of 11 patients enrolled in the study, 1 was readmitted for symptomatic hyponatremia. Device data completeness ranged from 78 to 93% with the exception of oxygen saturation (25% completeness). The patient with hyponatremia had a significantly lower baseline level of activity compared with other patients. Nonreadmitted patient activity variables (steps, calories, and distance) decreased by 48-52% after the operation (P < 0.001). The activity variables for the patient with hyponatremia were statistically unchanged after the operation; however, the patient did experience a significant decrease in heart rate compared with baseline., Conclusion: Deployment of a wrist-based physiologic tracking device is feasible for surgical patients in elective clinical practice. Overall, the device was associated with good patient adherence and high patient satisfaction. Patient activity significantly decreased after surgery. A significant decrease in heart rate was detected in a patient with hyponatremia who required readmission, which reflects the known intravascular volume expansion in this state.

Objective: Visual field (VF) outcomes are commonly reported in neurosurgical case series; however, substantial variability can exist in VF testing and outcome reporting. We aimed to evaluate the challenges of VF testing and to develop detailed recommendations for VF outcome reporting by analyzing results from an ongoing, multicenter study of transsphenoidal pituitary surgery., Methods: VF testing results were collected during a prospective, multicenter clinical trial evaluating patient outcomes after transsphenoidal surgery for nonfunctioning pituitary adenomas (TRANSSPHER). Two independent ophthalmologists reviewed reliability and outcomes of all VF studies. Preoperative and postoperative VF studies were evaluated individually and as preoperative/postoperative pairs., Results: Suboptimal perimetry field settings were reported in 37% of VF studies. Automated reliability criteria flagged 25%-29% of VF studies as unreliable, whereas evaluation by 2 independent ophthalmologists flagged 16%-28%. Agreement between automated criteria and raters for VF reliability was inconsistent (κ coefficients = 0.55-0.83), whereas agreement between the 2 raters was substantial to almost perfect (κ coefficients = 0.78-0.83). Most patients demonstrated improvement after surgery (rater 1, 67%; rater 2, 60%), with substantial rater agreement on outcomes for paired examinations (κ coefficient = 0.62)., Conclusions: VF outcome studies demonstrated significant variability of test parameters and patient performance. Perimetry field settings varied among patients and for some patients varied preoperatively versus postoperatively. Reliance on automated criteria alone could not substitute for independent ophthalmologist review of test reliability. Standardized guidelines for VF data collection and reporting could increase reliability of results and allow better comparisons of outcomes in future studies., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The minimal clinically important difference (MCID) is defined as the smallest change in health-related quality of life (QOL) that patients consider meaningful. The MCID is essential for determining clinically significant changes, rather than simply statistically significant changes, in QOL scores. The Anterior Skull Base Nasal Inventory-12 (ASK Nasal-12), a site-specific sinonasal QOL instrument, has emerged as a standard instrument for assessing QOL in patients who have undergone endonasal transsphenoidal surgery., Objective: To determine the MCID for the ASK Nasal-12., Methods: Distribution- and anchor-based methods were used to determine the MCID for the ASK Nasal-12 based on raw data from a multicenter prospective QOL study of 218 patients., Results: Two distribution-based statistical methods, the one-half standard deviation method and the effect-size method, both yielded MCIDs of 0.37 (medium effect). The first anchor-based method, using the 2-wk postoperative overall nasal functioning item as the anchor, yielded an MCID of 0.31. The second anchor-based method, using the 2-wk postoperative Short Form Health Survey 8 bodily pain item as the anchor, yielded an MCID of 0.29., Conclusion: The largest MCID obtained for the ASK Nasal-12 using 4 statistical methods 2 wk postoperatively was 0.37. This information provides clinicians with an essential context for determining the clinical significance of changes in QOL scores after interventions. Our results will help clinicians better interpret QOL scores and design future studies that are powered to detect meaningful QOL changes.

OBJECTIVE The objective of this study was to evaluate the feasibility of using confocal reflectance microscopy (CRM) ex vivo to differentiate adenoma from normal pituitary gland in surgical biopsy specimens. CRM allows for rapid, label-free evaluation of biopsy specimens with cellular resolution while avoiding some limitations of frozen section analysis. METHODS Biopsy specimens from 11 patients with suspected pituitary adenomas were transported directly to the pathology department. Samples were immediately positioned and visualized with CRM using a confocal microscope located in the same area of the pathology department where frozen sections are prepared. An H & E-stained slide was subsequently prepared from imaged tissue. A neuropathologist compared the histopathological characteristics of the H & E-stained slide and the matched CRM images. A second neuropathologist reviewed images in a blinded fashion and assigned diagnoses of adenoma or normal gland. RESULTS For all specimens, CRM contrasted cellularity, tissue architecture, nuclear pleomorphism, vascularity, and stroma. Pituitary adenomas demonstrated sheets and large lobules of cells, similar to the matched H & E-stained slides. CRM images of normal tissue showed scattered small lobules of pituitary epithelial cells, consistent with matched H & E-stained images of normal gland. Blinded review by a neuropathologist confirmed the diagnosis in 15 (94%) of 16 images of adenoma versus normal gland. CONCLUSIONS CRM is a simple, reliable approach for rapidly evaluating pituitary adenoma specimens ex vivo. This technique can be used to accurately differentiate between pituitary adenoma and normal gland while preserving biopsy tissue for future permanent analysis, immunohistochemical studies, and molecular studies.

OBJECTIVE The goal of this study was to determine the interrater and intrarater reliability of the Knosp grading scale for predicting pituitary adenoma cavernous sinus (CS) involvement. METHODS Six independent raters (3 neurosurgery residents, 2 pituitary surgeons, and 1 neuroradiologist) participated in the study. Each rater scored 50 unique pituitary MRI scans (with contrast) of biopsy-proven pituitary adenoma. Reliabilities for the full scale were determined 3 ways: 1) using all 50 scans, 2) using scans with midrange scores versus end scores, and 3) using a dichotomized scale that reflects common clinical practice. The performance of resident raters was compared with that of faculty raters to assess the influence of training level on reliability. RESULTS Overall, the interrater reliability of the Knosp scale was "strong" (0.73, 95% CI 0.56-0.84). However, the percent agreement for all 6 reviewers was only 10% (26% for faculty members, 30% for residents). The reliability of the middle scores (i.e., average rated Knosp Grades 1 and 2) was "very weak" (0.18, 95% CI -0.27 to 0.56) and the percent agreement for all reviewers was only 5%. When the scale was dichotomized into tumors unlikely to have intraoperative CS involvement (Grades 0, 1, and 2) and those likely to have CS involvement (Grades 3 and 4), the reliability was "strong" (0.60, 95% CI 0.39-0.75) and the percent agreement for all raters improved to 60%. There was no significant difference in reliability between residents and faculty (residents 0.72, 95% CI 0.55-0.83 vs faculty 0.73, 95% CI 0.56-0.84). Intrarater reliability was moderate to strong and increased with the level of experience. CONCLUSIONS Although these findings suggest that the Knosp grading scale has acceptable interrater reliability overall, it raises important questions about the "very weak" reliability of the scale's middle grades. By dichotomizing the scale into clinically useful groups, the authors were able to address the poor reliability and percent agreement of the intermediate grades and to isolate the most important grades for use in surgical decision making (Grades 3 and 4). Authors of future pituitary surgery studies should consider reporting Knosp grades as dichotomized results rather than as the full scale to optimize the reliability of the scale.

Objective: The comparative efficacy of microscopic and fully endoscopic transsphenoidal surgery for pituitary adenomas has not been well studied despite the adoption of fully endoscopic surgery by many pituitary centers. The influence of surgeon experience has also not been examined in this setting. The authors therefore compared the extent of tumor resection (EOR) and the endocrine outcomes of 1 very experienced surgeon performing a microscopic transsphenoidal surgery technique with those of a less experienced surgeon using a fully endoscopic transsphenoidal surgery technique for resection of nonfunctioning pituitary adenomas in a concurrent series of patients., Methods: Post hoc analysis was conducted of a cohort of adult patients prospectively enrolled in a pituitary adenoma quality-of-life study between October 2011 and June 2014. Patients were followed up for 6 months after surgery. Patients were treated either by a less experienced surgeon (100 independent cases) who practices fully endoscopic surgery exclusively or by a very experienced surgeon (1800 independent cases) who practices microscopic surgery exclusively. Patient demographic characteristics, tumor characteristics, hypopituitarism, complications, and length of hospital stay were analyzed. Tumor volumes and EOR were determined by formal volumetric analysis involving manual segmentation of MR images performed before surgery and within 6 months after surgery. Logistic regression analysis was used to determine predictors of EOR., Results: Fifty-five patients underwent fully endoscopic transsphenoidal surgery, and 80 patients underwent fully microscopic transsphenoidal surgery. The baseline characteristics of the 2 treatment groups were well matched. EOR was similar between the endoscopic and microscopic groups, respectively, as estimated by gross-total resection rate (78.2% vs 81.3%, p = 0.67), percentage of tumor resected (99.2% vs 98.7%, p = 0.42), and volume of residual tumor (0.12 cm(3) vs 0.20 cm(3), p = 0.41). Multivariate modeling suggested that preoperative tumor volume was the most important predictor of EOR (p = 0.001). No difference was found in the development of anterior gland dysfunction (p > 0.14), but there was a higher incidence of permanent posterior gland dysfunction in the microscopic group (p = 0.04). Combined rates of major complications and unplanned readmissions were lower in the endoscopic group (p = 0.02), but individual complications were not significantly different., Conclusions: A less experienced surgeon using a fully endoscopic technique was able to achieve outcomes similar to those of a very experienced surgeon using a microscopic technique in a cohort of patients with nonfunctioning tumors smaller than 60 cm(3). The study raises the provocative notion that certain advantages afforded by the fully endoscopic technique may impact the learning curve in pituitary surgery for nonfunctioning adenomas.

Background: Unplanned readmission after surgical procedures is an important quality metric. Yet, readmission rates and causes have not been evaluated for patients after transsphenoidal surgery for pituitary tumors., Objective: To analyze unplanned 30-day readmissions at a pituitary center and to encourage the development of effective clinical pathways to prevent readmission., Methods: A retrospective review of adult patients who underwent transsphenoidal surgery for pituitary lesions at Barrow Neurological Institute (January 2011-March 2014) was performed to identify causes of unplanned readmission within 30 days of surgery. Patient demographics, tumor details, surgical complications, and endocrine function were documented., Results: Of 303 patients who had transsphenoidal surgery, 27 (8.9%) were readmitted within 30 days. Most of the 27 (15 [55.6%]) had delayed hyponatremia. Other causes were diabetes insipidus (4 [14.8%]), adrenal insufficiency (2 [7.4%]), and cerebrospinal fluid leak, epistaxis, cardiac arrhythmia, pneumonia, urinary tract infection, and hypoglycemia (1 each [3.7%]). Outpatient sodium screening was performed as needed. In cases of hyponatremia, the mean postoperative day of readmission was day 8 (range, 6-12 days) and the mean serum sodium was 119 mmol/L (range, 111-129 mmol/L). Numerous patient and surgical factors were examined, and no specific predictors of readmission were identified. We developed an outpatient care pathway for managing hyponatremia with the goal of improving readmission rates., Conclusion: This study establishes a quality benchmark for readmission rates after transsphenoidal surgery for pituitary lesions and identifies delayed hyponatremia as the primary cause. Implementation of an outpatient care pathway for managing hyponatremia may improve readmission rates.

Object: Despite the widespread adoption of endoscopic transsphenoidal surgery for pituitary adenomas, the sinonasal quality of life (QOL) and health status in patients who have undergone this technique have not been compared with these findings in patients who have undergone the traditional direct uninostril microsurgical technique. In this study, the authors compared the sinonasal QOL and patient-reported health status after use of these 2 surgical techniques., Methods: The study design was a nonblinded prospective cohort study. Adult patients with sellar pathology and planned transsphenoidal surgery were screened at 4 pituitary centers in the US between October 2011 and August 2013. The primary end point of the study was postoperative patient-reported sinonasal QOL as measured by the Anterior Skull Base Nasal Inventory-12 (ASK Nasal-12). Supplementary end points included patient-reported health status estimated by the 8-Item Short Form Health Survey (SF-8) and EuroQol (EQ)-5D-5L instruments, and sinonasal complications. Patients were followed for 6 months after surgery., Results: A total of 301 patients were screened and 235 were enrolled in the study. Of these, 218 were analyzed (111 microsurgery patients, 107 endoscopic surgery patients). Demographic and tumor characteristics were similar between groups (p ≥ 0.12 for all comparisons). The most common complication in both groups was sinusitis (7% in the microsurgery group, 13% in the endoscopic surgery group; p = 0.15). Patients treated with the endoscopic technique were more likely to have postoperative nasal debridements (p < 0.001). The ASK Nasal-12 and SF-8 scores worsened substantially for both groups at 2 weeks after surgery, but then returned to baseline at 3 months. At 3 months after surgery, patients treated with endoscopy reported statistically better sinonasal QOL compared with patients treated using the microscopic technique (p = 0.02), but there were no significant differences at any of the other postoperative time points., Conclusions: This is the first multicenter study to examine the effect of the transsphenoidal surgical technique on sinonasal QOL and health status. The study showed that surgical technique did not significantly impact these patient-reported measures when performed at high-volume centers. Clinical trial registration no.: NCT01504399 ( clinicaltrials.gov ).

Object: Treatment of craniopharyngiomas is one of the most demanding and controversial neurosurgical procedures performed. The authors sought to determine the factors associated with hospital charges and fees for craniopharyngioma treatment to identify possible opportunities for improving the health care economics of inpatient care., Methods: The authors analyzed the hospital discharge database of the Nationwide Inpatient Sample (NIS) covering the period from 2007 through 2011 to examine national treatment trends for adults (that is, those older than 18 years) who had undergone surgery for craniopharyngioma. To predict the drivers of in-hospital charges, a multistep regression model was developed that accounted for patient demographics, acuity measures, comorbidities, hospital characteristics, and complications., Results: The analysis included 606 patients who underwent resection of craniopharyngioma; 353 resections involved a transsphenoidal approach (58%) and 253 a transfrontal approach (42%). The mean age (± SD) of patients was 47.7 ± 16.3 years. The average hospital length of stay (LOS) was 7.6 ± 9 days. The mean hospital charge (± SD) was $92,300 ± $83,356. In total, 48% of the patients experienced postoperative diabetes insipidus or an electrolyte abnormality. A multivariate regression model demonstrated that LOS, hospital volume for the selected procedure, the surgical approach, postoperative complications, comorbidities, and year of surgery were all significant predictors of in-hospital charges. The statistical model accounted for 54% of the variance in in-hospital charge., Conclusions: This analysis of inpatient hospital charges in patients undergoing craniopharyngioma surgery identified key drivers of charges in the perioperative period. Prospective studies designed to evaluate the long-term resource utilization in this complex patient population would be a useful future direction.

Unlabelled: OBJECT.: An increasingly important measure in the health care field is utilization of hospital resources, particularly in the context of emerging surgical techniques. Despite the recent widespread adoption of the endoscopic transsphenoidal approach for pituitary lesion surgery, the health care resources utilized with this approach have not been compared with those utilized with the traditional microscopic approach. The purpose of this study was to determine the drivers of resource utilization by comparing hospital charges for patients with pituitary tumors who had undergone either endoscopic or microscopic transsphenoidal surgery., Methods: A complete accounting of all hospital charges for 166 patients prospectively enrolled in a surgical quality-of-life study at a single pituitary center during October 2011-June 2013 was undertaken. Patients were assigned to surgical technique group according to surgeon preference and then managed according to a standard postoperative institutional set of orders. Individual line-item charges were assigned to categories (such as pharmacy, imaging, surgical, laboratory, room, pathology, and recovery unit), and univariate and multivariate statistical analyses were conducted., Results: Of the 166 patients, 99 underwent microscopic surgery and 67 underwent endoscopic surgery. Baseline demographic descriptors and tumor characteristics did not differ significantly. Mean total hospital charges were $74,703 ± $15,142 and $72,311 ± $16,576 for microscopic and endoscopic surgery patients, respectively (p = 0.33). Furthermore, other than for pathology, charge categories did not differ significantly between groups. A 2-step multivariate regression model revealed that length of stay was the most influential variable, followed by a diagnosis of Cushing's disease, and then by endoscopic surgical technique. The model accounts for 42% of the variance in hospital charges., Conclusions: Study findings suggest that adoption of the endoscopic transsphenoidal technique for pituitary lesions does not adversely affect utilization of resources for inpatients. The primary drivers of hospital charges, in order of importance, were length of stay, a diagnosis of Cushing's disease, and, to a lesser extent, use of the endoscopic technique. This study also highlights the influence of individual surgeon practice patterns on resource utilization.