Elevated risk of recurrence and retreatment for silent pituitary adenomas.

PURPOSE: Pituitary adenomas are the most common tumor of the pituitary gland and comprise nearly 15% of all intracranial masses. These tumors are stratified into functional or silent categories based on their pattern of hormone expression and secretion. Preliminary evidence supports differential clinical outcomes between some functional pituitary adenoma (FPA) subtypes and silent pituitary adenoma (SPA) subtypes. METHODS: We collected and analyzed the medical records of all patients undergoing resection of SPAs or FPAs from a single high-volume neurosurgeon between 2007 and 2018 at Brigham and Women's Hospital. Descriptive statistics and the Mantel-Cox log-rank test were used to identify differences in outcomes between these cohorts, and multivariate logistic regression was used to identify predictors of radiographic recurrence for SPAs. RESULTS: Our cohort included 88 SPAs and 200 FPAs. The majority of patients in both cohorts were female (48.9% of SPAs and 63.5% of FPAs). SPAs were larger in median diameter than FPAs (2.1 cm vs. 1.2 cm, p < 0.001). The most frequent subtypes of SPA were gonadotrophs (55.7%) and corticotrophs (30.7%). Gross total resection (GTR) was achieved in 70.1% of SPA resections and 86.0% of FPA resections (p < 0.001). SPAs had a higher likelihood of recurring (hazard ratio [HR] 3.2, 95% confidence interval [95%CI] 1.6-7.2) and a higher likelihood of requiring retreatment for recurrence (HR 2.5; 95%CI 1.0-6.1). Subset analyses revealed that recurrence and retreatment were more both likely for subtotally resected SPAs than subtotally resected FPAs, but this pattern was not observed in SPAs and FPAs after GTR. Among SPAs, recurrence was associated with STR (odds ratio [OR] 9.3; 95%CI 1.4-64.0) and younger age (OR 0.92 per year; 95%CI 0.88-0.98) in multivariable analysis. Of SPAs that recurred, 12 of 19 (63.2%) were retreated with repeat surgery (n = 11) or radiosurgery (n = 1), while the remainder were observed (n = 7).There were similar rates of recurrence across different SPA subtypes. CONCLUSION: Patients undergoing resection of SPAs should be closely monitored for disease recurrence through more frequent clinical follow-up and diagnostic imaging than other adenomas, particularly among patients with STR and younger patients. Several patients can be observed after radiographic recurrence, and the decision to retreat should be individualized. Longitudinal clinical follow-up of SPAs, including an assessment of symptoms, endocrine function, and imaging remains critical.

Long-Term Changes in the Size of Pituitary Microadenomas.

BACKGROUND: The estimated prevalence of pituitary lesions is 10% to 38.5% in radiologic studies. However, how frequently these incidental lesions should be monitored by serial pituitary magnetic resonance imaging (MRI) remains unclear. OBJECTIVE: To evaluate changes in pituitary microadenomas over time. DESIGN: Retrospective, longitudinal cohort study. SETTING: Mass General Brigham, Boston, Massachusetts. PATIENTS: Evidence of pituitary microadenoma from MRI. MEASUREMENTS: Dimensions of pituitary microadenomas. RESULTS: During the study period (from 2003 to 2021), 414 patients with pituitary microadenomas were identified. Of the 177 patients who had more than 1 MRI, 78 had no change in the size of the microadenoma over time, 49 had an increase in size, 34 had a decrease in size, and 16 had both an increase and decrease in size. By linear mixed model analysis, the estimated slope was 0.016 mm/y (95% CI, -0.037 to 0.069). In the subgroup analysis, pituitary adenomas with a baseline size of 4 mm or less tended to increase in size. The estimated slope was 0.09 mm/y (CI, 0.020 to 0.161). In contrast, in the subgroup with baseline tumor size greater than 4 mm, the size tended to decrease. The estimated slope was -0.063 mm/y (CI, -0.141 to 0.015). LIMITATION: Retrospective cohort, some patients were lost to follow-up for unknown reasons, and data were limited to local large institutions. CONCLUSION: During the study period, approximately two thirds of the microadenomas remained unchanged or decreased in size. The growth, if any, was slow. These findings suggest that less frequent pituitary MRI surveillance for patients with incidental pituitary microadenomas may be safe. PRIMARY FUNDING SOURCE: None.

Vascular anomalies in patients with growth hormone-secreting pituitary adenomas: illustrative case report and systematic review of the literature.

PURPOSE: Endonasal resection is the first-line treatment for patients harboring growth hormone (GH)-secreting pituitary adenomas. The complexity of the parasellar neurovascular structures makes pre-operative diagnostic imaging essential to understanding the anatomy of this region. We aimed to describe vascular anomalies in acromegalic patients and emphasize their relevance for surgery and preoperative planning. METHODS: A systematic review following the PRISMA statement was performed in July 2021. RESULTS: Thirty-three studies were evaluated. Elevated GH and insulin-like growth factor-1 (IGF-1) levels are linked to the occurrence of cardiovascular risk factors. This is attributed to endothelial dysfunction, mainly caused by changes in flow-mediated dilatation (FMD), which is probably the main cause of vascular anomalies in acromegaly. The occurrence of protrusions of the internal carotid artery (ICA) (35-53%), a narrow intercarotid distance, and an asymmetrical course was described. In 13-18% of acromegalic patients, the presence of an intracerebral aneurysm could be reported (incidence in the general population:0.8-1.3%). The selected studies were however performed with a small patient sample (range:1-257). We present a case report of a 57y/o male patient with anomalies of the ICA ("kissing carotid arteries") harboring a GH-secreting adenoma, which was resected via an endoscopic endonasal approach. CONCLUSIONS: There is an association between acromegaly and endothelial dysfunction, which increases cardiovascular risk factors and vascular anomalies. Preoperative vascular imaging, e.g., CT angiography, should be implemented as a standard to identify patients at risk and estimate surgical morbidity. However, no evidence-based recommendations exist so far, so future studies are necessary.

Metastatic pituitary tumors: an institutional case series.

PURPOSE: Pituitary carcinomas are a rare entity that respond poorly to multimodal therapy. Patients follow a variable disease course that remains ill-defined. METHODS: We present an institutional case series of patients treated for pituitary carcinomas over a 30-year period from 1992 to 2022. A systematic review was conducted to identify prior case series of patients with pituitary carcinomas. RESULTS: Fourteen patients with a mean age at pituitary carcinoma diagnosis of 52.5 years (standard deviation [SD] 19.4) met inclusion criteria. All 14 patients had tumor subtypes confirmed by immunohistochemistry and hormone testing, with the most common being ACTH-producing pituitary adenomas (n = 12). Patients had a median progression-free survival (PFS) of 1.4 years (range 0.7-10.0) and a median overall survival (OS) of 8.4 years (range 2.3-24.0) from pituitary adenoma diagnosis. Median PFS and OS were 0.6 years (range 0.0-2.2) and 1.5 years (range 0.1-9.6) respectively upon development of metastases. Most patients (n = 12) had locally invasive disease to the cavernous sinus, dorsum sellae dura, or sphenoid sinus prior to metastasis. Common sites of metastasis included the central nervous system, liver, lung, and bone. In a pooled analysis including additional cases from the literature, treatment of metastases with chemotherapy or a combination of radiation therapy and chemotherapy significantly prolonged PFS (p = 0.02), while failing to significantly improve OS (p = 0.14). CONCLUSION: Pituitary carcinomas are highly recurrent, heterogenous tumors with variable responses to treatment. Multidisciplinary management with an experienced neuro-endocrine and neuro-oncology team is needed given the unrelenting nature of this disease.

Alcohol intake and risk of pituitary adenoma.

BACKGROUND: The association between alcohol intake and incidence of pituitary adenoma has not been reported previously. We examined this association in three large, prospective cohort studies. METHODS: Using data from the Nurses' Health Study, Nurses' Health Study II, and Health Professionals Follow-Up Study, we computed multivariable-adjusted hazard ratios (MVHR) and 95% confidence intervals (CI) for pituitary adenoma by levels of alcohol intake using Cox proportional hazards regression. RESULTS: We identified 292 incident cases of pituitary adenoma (225 among women, 67 among men) among 235,973 participants with 6,548,732 person-years of follow-up. Compared with intake of ≤ 0.5 g/day, cumulative average alcohol intake in all categories was associated with reduced risk of pituitary adenoma (MVHR = 0.60, 95% CI 0.43-0.83 for 0.5-≤ 2 g/day, MVHR = 0.57, 95% CI 0.41-0.79 for > 2.0-≤ 8.0, MVHR = 0.70, 95% CI 0.47-1.04 for > 8.0-≤ 15.0, and MVHR = 0.51, 95% CI 0.32-0.83 for > 15.0 g/day). Significant inverse findings were present in women and were similar but non-significant in men. For specific alcoholic beverages, inverse associations were statistically significant for total wine (MVHR = 0.58, 95% CI 0.43-0.79 comparing 0.5-≤ 2 to ≤ 0.5 g/day), red wine (MVHR = 0.65, 95% CI 0.46-0.92 comparing 0.5-≤ 2 to ≤ 0.5 g/day), and white wine (MVHR = 0.72, 95% CI 0.53-0.97 comparing 0.5-≤ 2 to ≤ 0.5 g/day). Results were consistent using baseline intake, recent intake, and with an 8-year lag. CONCLUSION: In three prospective cohorts, compared to almost no consumption, alcohol consumption was associated with reduced risk of pituitary adenoma. Sensitivity analyses suggest that these results are unlikely to be the result of reverse causation or diagnostic bias.

Interactive effects of CO2 , temperature, irradiance, and nutrient limitation on the growth and physiology of the marine cyanobacterium Synechococcus (Cyanophyceae).

The marine cyanobacterium Synechococcus elongatus was grown in a continuous culture system to study the interactive effects of temperature, irradiance, nutrient limitation, and the partial pressure of CO2 (pCO2) on its growth and physiological characteristics. Cells were grown on a 14:10 h light:dark cycle at all combinations of low and high irradiance (50 and 300 µmol photons ⋅ m-2 ⋅ s-1 , respectively), low and high pCO2 (400 and 1000 ppmv, respectively), nutrient limitation (nitrate-limited and nutrient-replete conditions), and temperatures of 20-45°C in 5°C increments. The maximum growth rate was ~4.5 · d-1 at 30-35°C. Under nutrient-replete conditions, growth rates at most temperatures and irradiances were about 8% slower at a pCO2 of 1000 ppmv versus 400 ppmv. The single exception was 45°C and high irradiance. Under those conditions, growth rates were ~45% higher at 1000 ppmv. Cellular carbon:nitrogen ratios were independent of temperature at a fixed relative growth rate but higher at high irradiance than at low irradiance. Initial slopes of photosynthesis-irradiance curves were higher at all temperatures under nutrient-replete versus nitrate-limited conditions; they were similar at all temperatures under high and low irradiance, except at 20°C, when they were suppressed at high irradiance. A model of phytoplankton growth in which cellular carbon was allocated to structure, storage, or the light or dark reactions of photosynthesis accounted for the general patterns of cell composition and growth rate. Allocation of carbon to the light reactions of photosynthesis was consistently higher at low versus high light and under nutrient-replete versus nitrate-limited conditions.

Epidemiology of common and uncommon adult pituitary tumors in the U.S. according to the 2017 World Health Organization classification.

PURPOSE: To examine the contemporary epidemiology of adult pituitary tumors with a particular focus on uncommon tumor types, using the 2017 WHO Classification of pituitary tumors. METHODS: Adult patients presenting with a pituitary or sellar tumor between 2004 and 2017 were identified from the U.S. National Cancer Database, with tumor type categorized according to the 2017 WHO classification. Descriptive epidemiological statistics were evaluated and reported for all pituitary tumor types and subtypes. RESULTS: 113,349 adults with pituitary tumors were identified, 53.0% of whom were female. The majority of pituitary tumors were pituitary adenomas (94.0%), followed by craniopharyngiomas (3.8%). Among pituitary adenomas, whereas 71.6% of microadenomas presented in females, only 46.7% of macroadenomas and 41.3% of giant adenomas did (p < 0.001). For craniopharyngiomas, 71.2% were adamantinomatous and 28.8% were papillary, with adamantinomatous tumors associated with Black non-Hispanic race/ethnicity (ORadj = 2.44 vs. White non-Hispanic, 99.9 %CI = 1.25-4.75, p < 0.001) in multivariable analysis. The remaining 0.7% (n = 676) of pathology-confirmed pituitary tumor types were composed of: 21% tumors of the posterior pituitary, 16% chordomas, 11% pituitary carcinomas (i.e. adenohypophyseal histology with metastasis; herein most frequently to bone), 10% meningiomas, 8% germ cell tumors, 7% hematolymphoid (largely DLBCLs), and 4% neuronal/paraneuronal (largely gangliogliomas). Pituitary carcinomas and posterior pituitary tumors demonstrated a male predilection (62.2% and 56.0%, respectively), whereas sellar meningiomas predominated in females (84.1%). Age, race/ethnicity, tumor size, and overall survival further varied across uncommon pituitary tumor types. CONCLUSIONS: Our findings provide a detailed contemporary dissection of the epidemiology of common and uncommon adult pituitary tumors in the context of WHO2017.

Characterization of a paradoxical post-operative increase in serum cortisol in Cushing disease.

PURPOSE: In Cushing disease, early post-operative serum cortisol fluctuations have not been adequately characterized, and their association with initial remission and recurrence is unclear. METHODS: A retrospective cohort study of patients with Cushing disease was conducted at two institutions. A "riser" was defined a priori as a paradoxical increase in serum cortisol with an immediate incremental increase in serum cortisol over three consecutive cortisol draws separated by roughly 6-h (definition 1). Post hoc analyses used a definition of two consecutive increases (definition 2). Risers were compared to non-risers for initial remission and time-to-recurrence. RESULTS: A total of 505 patients with Cushing disease were screened, and 469 had adequate data for group assignment. Analysis of post-operative cortisol showed a subgroup of "risers" with a frequency of 3.6% for definition 1 and 42.6% for definition 2. In these patients, cortisol levels were significantly higher until approximately 36 h post-operatively, and cortisol had a significantly longer mean serum half-life. In the post hoc analysis, definition 2 risers had a lower remission rate compared to non-risers (162/196, 82.7%, versus 243/264, 92.0%) with an odds ratio of 0.41 (0.23-0.73; p = 0.003). For both definitions, recurrence was similar between groups. CONCLUSIONS: We found that almost half of Cushing disease patients experienced a temporary increase in serum cortisol level during the early post-operative period. Serum cortisol half-life was longer, and the remission rates were lower, however, recurrence rates were similar to non-risers.

Predictors of postoperative biochemical remission in acromegaly.

PURPOSE: Acromegaly is a rare neuroendocrine condition that can lead to significant morbidity. Despite China's vast population size, studies on acromegaly remain sparse. This study aimed to investigate the clinical characteristics and predictors of biochemical remission after surgery for acromegaly using the China Acromegaly Patient Association (CAPA) database. METHODS: A retrospective nationwide study was conducted using patient-reported data from CAPA database between 1998 and 2018. The principal component analysis (PCA) and logistic regression analysis were employed to determine independent predictors of biochemical remission at 3 months in patients after surgery. RESULTS: Of the 546 surgical cases (mean age: 36.8 years; 59.5% females), macroadenomas and invasive tumors (Knosp score 3-4) were 83.9% and 64.1%, respectively. Ninety-five percent of patients were treated with endonasal surgery and 36.8% exhibited biochemical remission at 3-months postoperatively. The following independent predictors of biochemical remission were identified: preoperative growth hormone (GH) levels between 12 and 28 µg/L [odds ratio (OR) = 0.58; 95% confidence interval (CI), 0.37-0.92; p = 0.021], preoperative GH levels > 28 µg/L (OR = 0.55; 95% CI, 0.34-0.88; p = 0.013), macroadenoma (OR = 0.56; 95% CI, 0.32-0.96; p = 0.034), giant adenomas (OR = 0.14; 95% CI, 0.05-0.38; p < 0.001), Knosp score 3-4 (OR = 0.37; 95% CI, 0.24-0.57; p < 0.001), and preoperative medication usage (OR = 2.32; 95% CI, 1.46-3.70; p < 0.001). CONCLUSIONS: In this nationwide study spanning over two decades, we highlight that higher preoperative GH levels, large tumor size, and greater extent of tumor invasiveness are associated with a lower likelihood of biochemical remission at 3-months after surgery, while preoperative medical therapy increases the chance of remission.

Professor Rathke's gift to neurosurgery: the cyst, its diagnosis, surgical management, and outcomes.

PURPOSE: Rathke cleft cysts (RCC) are a target for transsphenoidal surgery when symptomatic; however, the surgical techniques and outcomes continue to be of interest. Our goal is to highlight nuances in diagnosis, surgical philosophy and techniques, and outcomes. METHODS: We retrospectively reviewed a single surgeon experience in a contemporary series of RCC from April 2008 through December 2019. The clinical presentation, radiographic studies, intraoperative findings, histopathological diagnosis, postoperative complications, and outcome data were recorded and analyzed. RESULTS: A total of 131 endoscopic endonasal operations were performed on 116 patients (30 male, 86 female), with an average age of 39 years. We identified 102 patients without prior surgery, and 14 patients with prior surgery elsewhere. Postoperative complications included transient diabetes insipidus (DI) (n = 23, 20%), permanent DI (n = 5, 4%), SIADH (n = 6, 5%), epistaxis (n = 6, 5%), postoperative infection (n = 3, 2.5%), postoperative CSF leak (n = 1, < 1%), intrasellar hematoma (n = 1, < 1%), and stroke (n = 1, < 1%). Visual improvement was observed in 74% (n = 31/42) of patients presenting with visual loss, and headache improvement in 86% (n = 80/93). Overall, the recurrence rate in our cohort was 11%, with a lower recurrence rate seen in males (p = 0.02). The median follow-up duration was 15.2 months (interquartile range 1.7-52.3) CONCLUSION: Our results reflect the philosophy of a conservative surgical approach, designed to preserve normal pituitary function, and avoid DI, while achieving the maximal feasible resection. Evacuation of the cyst contents and meticulous sampling of the cyst wall when possible for histopathological diagnosis are crucial. The postoperative relief of symptoms and signs is gratifying, as are the overall rates of recurrence and outcomes.

The epidemiology and management patterns of pediatric pituitary tumors in the United States.

PURPOSE: Hypothalamic-pituitary axis dysfunction and mass effect symptoms in the pediatric population can indicate a pituitary region tumor. Herein, we evaluate the epidemiology and management of this rare entity. METHODS: Pediatric patients (≤ 21yo) who presented from 2004 to 2017 with a pituitary tumor were evaluated from the U.S. National Cancer Database. The distributions and management patterns of pituitary tumors were assessed by patients' tumor type, age, sex, race/ethnicity, tumor size, and insurance status. RESULTS: 19.7% of intracranial tumors in the pediatric population originated in the pituitary region. 7653 pediatric patients with pituitary region tumors were identified, 68.2% of whom were female, with the tumors predominantly occurring in early adolescence (46.9%) and late adolescence (34.8%). The majority of pediatric pituitary region tumors were pituitary adenomas (77.9%), followed by craniopharyngiomas (18.1%) and germ cell tumors (1.6%). Girls demonstrated higher proportions of pituitary adenomas across all ages than boys. Asian/Pacific Islander patients were independently more likely to present at younger ages (mean 13.9yrs) and with germ cell tumors than patients of other races/ethnicities. Only 5.5% of patients were uninsured (referent), but they were independently more likely to present at older ages (mean 17.9yrs) and less likely to undergo surgery than patients with private insurance (OR = 1.93, 95% CI = 1.47-2.52, p < 0.001) or Medicaid (OR = 1.51, 95% CI = 1.14-2.00, p = 0.004). CONCLUSION: Pituitary region tumors comprise a significant fraction of intracranial pediatric tumors, particularly in adolescent girls. The differential diagnosis of pituitary tumor types differed significantly by patients' age, sex, and race/ethnicity. Uninsured patients were associated with delays in care and less surgical management.

Pituitary society expert Delphi consensus: operative workflow in endoscopic transsphenoidal pituitary adenoma resection.

PURPOSE: Surgical workflow analysis seeks to systematically break down operations into hierarchal components. It facilitates education, training, and understanding of surgical variations. There are known educational demands and variations in surgical practice in endoscopic transsphenoidal approaches to pituitary adenomas. Through an iterative consensus process, we generated a surgical workflow reflective of contemporary surgical practice. METHODS: A mixed-methods consensus process composed of a literature review and iterative Delphi surveys was carried out within the Pituitary Society. Each round of the survey was repeated until data saturation and > 90% consensus was reached. RESULTS: There was a 100% response rate and no attrition across both Delphi rounds. Eighteen international expert panel members participated. An extensive workflow of 4 phases (nasal, sphenoid, sellar and closure) and 40 steps, with associated technical errors and adverse events, were agreed upon by 100% of panel members across rounds. Both core and case-specific or surgeon-specific variations in operative steps were captured. CONCLUSIONS: Through an international expert panel consensus, a workflow for the performance of endoscopic transsphenoidal pituitary adenoma resection has been generated. This workflow captures a wide range of contemporary operative practice. The agreed "core" steps will serve as a foundation for education, training, assessment and technological development (e.g. models and simulators). The "optional" steps highlight areas of heterogeneity of practice that will benefit from further research (e.g. methods of skull base repair). Further adjustments could be made to increase applicability around the world.

Aggressive pituitary neuroendocrine tumors: current practices, controversies, and perspectives, on behalf of the EANS skull base section.

Aggressive pituitary neuroendocrine tumors (APT) account for 10% of pituitary tumors. Their management is a rapidly evolving field of clinical research and has led pituitary teams to shift toward a neuro-oncological-like approach. The new terminology "Pituitary neuroendocrine tumors" (PitNet) that was recently proposed to replace "pituitary adenomas" reflects this change of paradigm. In this narrative review, we aim to provide a state of the art of actual knowledge, controversies, and recommendations in the management of APT. We propose an overview of current prognostic markers, including the recent five-tiered clinicopathological classification. We further establish and discuss the following recommendations from a neurosurgical perspective: (i) surgery and multi-staged surgeries (without or with parasellar resection in symptomatic patients) should be discussed at each stage of the disease, because it may potentialize adjuvant medical therapies; (ii) temozolomide is effective in most patients, although 30% of patients are non-responders and the optimal timeline to initiate and interrupt this treatment remains questionable; (iii) some patients with selected clinicopathological profiles may benefit from an earlier local radiotherapy and/or chemotherapy; (iv) novel therapies such as VEGF-targeted therapies and anti-CTLA-4/anti-PD1 immunotherapies are promising and should be discussed as 2nd or 3rd line of treatment. Finally, whether neurosurgeons have to operate on "pituitary adenomas" or "PitNets," their role and expertise remain crucial at each stage of the disease, prompting our community to deal with evolving concepts and therapeutic resources.

Multidisciplinary management of acromegaly: A consensus.

The 13th Acromegaly Consensus Conference was held in November 2019 in Fort Lauderdale, Florida, and comprised acromegaly experts including endocrinologists and neurosurgeons who considered optimal approaches for multidisciplinary acromegaly management. Focused discussions reviewed techniques, results, and side effects of surgery, radiotherapy, and medical therapy, and how advances in technology and novel techniques have changed the way these modalities are used alone or in combination. Effects of treatment on patient outcomes were considered, along with strategies for optimizing and personalizing therapeutic approaches. Expert consensus recommendations emphasize how best to implement available treatment options as part of a multidisciplinary approach at Pituitary Tumor Centers of Excellence.

Interactive Effects of CO2 , Temperature, Irradiance, and Nutrient Limitation on the Growth and Physiology of the Marine Diatom Thalassiosira pseudonana (Coscinodiscophyceae).

The marine diatom Thalassiosira pseudonana was grown in continuous culture systems to study the interactive effects of temperature, irradiance, nutrient limitation, and the partial pressure of CO2 (pCO2 ) on its growth and physiological characteristics. The cells were able to grow at all combinations of low and high irradiance (50 and 300 µmol photons · m-2  · s-1 , respectively, of visible light), low and high pCO2 (400 and 1,000 µatm, respectively), nutrient limitation (nitrate-limited and nutrient-replete conditions), and temperatures of 10-32°C. Under nutrient-replete conditions, there was no adverse effect of high pCO2 on growth rates at temperatures of 10-25°C. The response of the cells to high pCO2 was similar at low and high irradiance. At supraoptimal temperatures of 30°C or higher, high pCO2 depressed growth rates at both low and high irradiance. Under nitrate-limited conditions, cells were grown at 38 ± 2.4% of their nutrient-saturated rates at the same temperature, irradiance, and pCO2 . Dark respiration rates consistently removed a higher percentage of production under nitrate-limited versus nutrient-replete conditions. The percentages of production lost to dark respiration were positively correlated with temperature under nitrate-limited conditions, but there was no analogous correlation under nutrient-replete conditions. The results suggest that warmer temperatures and associated more intense thermal stratification of ocean surface waters could lower net photosynthetic rates if the stratification leads to a reduction in the relative growth rates of marine phytoplankton, and at truly supraoptimal temperatures there would likely be a synergistic interaction between the stresses from temperature and high pCO2 (lower pH).

The diagnosis and management of primary and iatrogenic soft tissue sarcomas of the sella.

PURPOSE: Soft tissue sarcoma (STS) of the sella is exceptionally rare. We conducted a case series, literature review, and nationwide analysis of primary and iatrogenic (radiation-associated) STS of the sella to define the clinical course of this entity. METHODS: This study employed a multi-institutional retrospective case review, literature review, and nationwide analysis using the National Cancer Database (NCDB). RESULTS: We report five patients who were diagnosed at three institutions with malignant STS of the sella. All patients presented with symptoms related to mass effect in the sellar region. All tumors extended to the suprasellar space, with the majority displaying extension into the cavernous sinus. All patients underwent an operation via a transsphenoidal approach with a goal of maximal safe tumor resection in four patients and biopsy for 1 patient. Histopathologic evaluation demonstrated STS in all patients. Post-operative adjuvant radiotherapy and chemotherapy were given to 2 and 1 out of 4 patients with known post-operative clinical course, respectively. The 1-year and 5-year overall survival rates were 100% (5/5) and 25% (1/4). Twenty-two additional reports of primary, non-iatrogenic STS of the sella were identified in the literature. Including the three cases from our series, treatment included resection in all cases, and adjuvant radiotherapy and chemotherapy were utilized in 50% (12/24) and 17% (4/24) of cases, respectively. The national prevalence of malignant STS is estimated to be 0.01% among all pituitary and sellar tumors within the NCDB. CONCLUSIONS: We report the prevalence and survival rates of STS of the sella. Multimodal therapy, including maximal safe resection, chemotherapy, and radiotherapy are necessary to optimize outcomes for this uncommon pathology.

Optimizing pre-, intra-, and postoperative management of patients with sellar pathology undergoing transsphenoidal surgery.

OBJECTIVE: Perioperative management of patients with sellar lesions is complex, requiring input from a multidisciplinary team of specialists for ongoing management of both endocrinological and neurosurgical issues. Here, the authors reviewed the experience of a single multidisciplinary center over 10 years to identify key postoperative practices that ensure positive outcomes for patients with sellar lesions who undergo transsphenoidal surgery. METHODS: The authors performed a retrospective review of all transsphenoidal operations carried out by the senior author at a single center from April 2008 through November 2018. They included only adult patients and recorded perioperative management. They also reviewed the evolution of clinical practices for perioperative care at their institution to identify strategies for ensuring positive patient outcomes, and they reviewed the literature on select related topics. RESULTS: In total, 1023 operations in 928 patients were reviewed. Of these, 712 operations were for pituitary adenomas (69.6%), and 122 were for Rathke cleft cysts (11.9%). The remainder included operations for craniopharyngiomas (3.6%), arachnoid cysts (1.7%), pituitary tumor apoplexy (1.0%), and other sellar pathologies (12.2%). Among the reviewed operations, the median hospital stay was 3 days (IQR 2-3). Patient management details during the pre-, intra-, and postoperative periods were identified, including both shared characteristics of all patients undergoing transsphenoidal surgery and unique characteristics that are specific to certain lesion types or patient populations. CONCLUSIONS: Patients with sellar lesions who undergo transsphenoidal surgery require complex, multidisciplinary perioperative care to monitor for common adverse events and to improve outcomes, but there is a dearth of high-quality evidence guiding most perioperative practices. Here, the authors reviewed practices at their institution across more than 1000 transsphenoidal operations that may help ensure successful patient outcomes.

Mapping cognitive and emotional networks in neurosurgical patients using resting-state functional magnetic resonance imaging.

Neurosurgery has been at the forefront of a paradigm shift from a localizationist perspective to a network-based approach to brain mapping. Over the last 2 decades, we have seen dramatic improvements in the way we can image the human brain and noninvasively estimate the location of critical functional networks. In certain patients with brain tumors and epilepsy, intraoperative electrical stimulation has revealed direct links between these networks and their function. The focus of these techniques has rightfully been identification and preservation of so-called "eloquent" brain functions (i.e., motor and language), but there is building momentum for more extensive mapping of cognitive and emotional networks. In addition, there is growing interest in mapping these functions in patients with a broad range of neurosurgical diseases. Resting-state functional MRI (rs-fMRI) is a noninvasive imaging modality that is able to measure spontaneous low-frequency blood oxygen level-dependent signal fluctuations at rest to infer neuronal activity. Rs-fMRI may be able to map cognitive and emotional networks for individual patients. In this review, the authors give an overview of the rs-fMRI technique and associated cognitive and emotional resting-state networks, discuss the potential applications of rs-fMRI, and propose future directions for the mapping of cognition and emotion in neurosurgical patients.

Surgical management of craniopharyngiomas in adult patients: a systematic review and consensus statement on behalf of the EANS skull base section.

BACKGROUND AND OBJECTIVE: Craniopharyngiomas are locally aggressive neuroepithelial tumors infiltrating nearby critical neurovascular structures. The majority of published surgical series deal with childhood-onset craniopharyngiomas, while the optimal surgical management for adult-onset tumors remains unclear. The aim of this paper is to summarize the main principles defining the surgical strategy for the management of craniopharyngiomas in adult patients through an extensive systematic literature review in order to formulate a series of recommendations. MATERIAL AND METHODS: The MEDLINE database was systematically reviewed (January 1970-February 2019) to identify pertinent articles dealing with the surgical management of adult-onset craniopharyngiomas. A summary of literature evidence was proposed after discussion within the EANS skull base section. RESULTS: The EANS task force formulated 13 recommendations and 4 suggestions. Treatment of these patients should be performed in tertiary referral centers. The endonasal approach is presently recommended for midline craniopharyngiomas because of the improved GTR and superior endocrinological and visual outcomes. The rate of CSF leak has strongly diminished with the use of the multilayer reconstruction technique. Transcranial approaches are recommended for tumors presenting lateral extensions or purely intraventricular. Independent of the technique, a maximal but hypothalamic-sparing resection should be performed to limit the occurrence of postoperative hypothalamic syndromes and metabolic complications. Similar principles should also be applied for tumor recurrences. Radiotherapy or intracystic agents are alternative treatments when no further surgery is possible. A multidisciplinary long-term follow-up is necessary.

Surgical and radiosurgical treatment strategies for Cushing's disease.

INTRODUCTION: Cushing's disease (CD) is rare disorder that should be adequately managed to optimize long-term prognosis. Treatment of CD is multidisciplinary and often includes surgical resection, adjuvant stereotactic radiosurgery (SRS), and medical treatment. Here we review surgical and radiosurgical treatment strategies for ACTH producing pituitary adenomas. METHODS: A comprehensive literature review was carried out to review remission and recurrence rates, and complications of surgical and SRS treatments of ACTH producing pituitary adenomas. RESULTS: Surgical resection plays a central role in the management of ACTH secreting pituitary adenomas and usually allows rapid endocrine remission that ranges from 69 to 90%. The most common complications after resection include some degree of new hypopituitarism, diabetes insipidus and CSF leak. Devastating complications, such as injury of vascular and neural structures, are very rare. Surgeon experience and adequate pre-operative imaging are important for safe and successful surgery. Endocrine recurrence rates after resection range from 9 to 30%. SRS is often employed for incompletely resected adenomas. Endocrine remission after SRS ranges from 35 to 72%. The most common complication of SRS is new anterior pituitary gland deficiency. Recurrence rates after GKRS range from 18 to 24%. CONCLUSIONS: Transsphenoidal resection of ACTH producing pituitary adenoma is a safe and highly effective procedure for CD in experienced hands. Radiosurgery is more frequently used as treatment of residual and recurrent adenoma and persistent CD. Long-term endocrine and imaging follow-up is important as delayed recurrences and hypopituitarism are not infrequent.