Surgery For Pituitary Tumors Research Articles

7790 A Non-interventional, Multinational, Phase IV Study to Evaluate the Long-Term Safety and Efficacy of Osilodrostat in Patients with Endogenous Cushing's Syndrome (LINC 6): 1-Year Real-World Interim Analysis

Abstract Disclosure: I. Bancos: Advisory Board Member; Self; Adrenas, Diurnal, Neurocrine, Spruce, HRA Pharmaceuticals, Sparrow, Recordati Rare Diseases, Xeris, Novo Nordisk, AstraZeneca, Corcept. Consulting Fee; Self; Adrenas, Diurnal, Neurocrine, Spruce, HRA Pharmaceuticals, Sparrow, Recordati Rare Diseases, Xeris, Novo Nordisk, AstraZeneca, Corcept. Grant Recipient; Self; Recordati, HRA Pharmaceuticals. Other; Self; Adrenas, Diurnal, Neurocrine, Spruce, HRA Pharmaceuticals, Sparrow, Recordati Rare Diseases, Xeris, Novo Nordisk, AstraZeneca, Corcept. E.B. Geer: Advisory Board Member; Self; Recordati Rare Diseases. Consulting Fee; Self; Lundbeck, Crinetics, HRA Pharmaceuticals, Recordati Rare Diseases, Sparrow, Xeris Pharmaceuticals (Strongbridge). Grant Recipient; Self; Xeris Pharmaceuticals (Strongbridge), Corcept, Recordati Rare Diseases, Sparrow. F. Castinetti: Consulting Fee; Self; HRA Pharmaceuticals, Recordati. Grant Recipient; Self; HRA Pharmaceuticals, Recordati. R. Feelders: Advisory Board Member; Self; Recordati. Consulting Fee; Self; HRA Pharmaceuticals, Recordati. Grant Recipient; Self; Corcept Therapeutics. M. Fleseriu: Advisory Board Member; Self; Recordati Rare Diseases. Consulting Fee; Self; Recordati Rare Diseases, Sparrow, Xeris Pharmaceuticals (Strongbridge). Grant Recipient; Self; Recordati Rare Diseases, Sparrow, Xeris Pharmaceuticals (Strongbridge). R. Pivonello: Consulting Fee; Self; Corcept Therapeutics, Recordati, Crinetics Pharmaceuticals, H Lundbeck. Grant Recipient; Self; Recordati, Corcept Therapeutics, Xeris Pharmaceuticals (Strongbridge), Neurocrine Biosciences. M. Reincke: Advisory Board Member; Self; Recordati Rare Diseases. Consulting Fee; Self; Recordati Rare Diseases, HRA Pharmaceuticals, Lundbeck, Crinetics. Grant Recipient; Self; Recordati Rare Diseases, HRA Pharmaceuticals, Lundbeck, Crinetics. Speaker; Self; Recordati Rare Diseases, HRA Pharmaceuticals, Lundbeck, Crinetics. A. Tabarin: Advisory Board Member; Self; Recordati Rare Diseases. Consulting Fee; Self; H Lundbeck, Crinetics, HRA Pharmaceuticals, Recordati Rare Diseases. J. Le Mouhaër: Employee; Self; Recordati. J. Stermenska: Employee; Self; Recordati. M. Maldonado: Employee; Self; Recordati. B.M. Biller: Advisory Board Member; Self; Recordati Rare Diseases. Consulting Fee; Self; H Lundbeck, Recordati Rare Diseases, Sparrow, Xeris Pharmaceuticals (Strongbridge). Introduction: Osilodrostat, a potent oral 11β-hydroxylase inhibitor, provides control of cortisol production and improves outcomes in patients (pts), as shown by the clinical development program of Cushing’s disease (CD; Fleseriu M et al. Lancet Diabetes Endocrinol 2021;9:847-75) leading to EMA approval for Cushing’s syndrome (CS) and FDA approval for CD. The prospective LINC 6 study (NCT05382156) evaluates long-term safety and efficacy of osilodrostat in routine clinical practice over a 3-­year follow-up of CS pts. Here, we report 1-year interim data. Methods: Pts aged ≥18 years with endogenous CS are being enrolled in countries where osilodrostat is approved and available (including USA and Europe), irrespective of prior osilodrostat use. Treatment decisions and follow-up are at investigator discretion. The primary endpoint is incidence of osilodrostat-related adverse events (AEs) and serious AEs, focusing on AEs related to hypocortisolism, accumulation of adrenal hormone precursors, QT prolongation and pituitary tumor enlargement. Secondary endpoints include change in mean urinary free cortisol (mUFC), serum cortisol and late-night salivary cortisol (LNSC). Evaluation of biochemical parameters is recommended at baseline, months 1 and 3, and every 3 months thereafter, as available. AEs are recorded at baseline and each visit. Analyses are descriptive. We report change for pts with assessments at baseline and every 3 months. Results: Of 106 pts enrolled at the 1-year interim analysis, 94 were included in the safety population: CD, n=78; non-CD CS, n=16 (adrenal adenoma, n=3; adrenal hyperplasia, n=3; ectopic, n=9; other, n=1). Mean (SD) age was 53.2 years (12.7); 70.2% (n=66) were female. Median (min-max) osilodrostat exposure and dose were 5.5 months (0.1-13.9) and 5.0 mg/day (1.0-60.0). 29 pts reported 109 AEs; 12 pts reported 44 AEs that were considered treatment related. Overall, the most common (≥5%) AEs were asthenia and vomiting (both n=6/109; 5.5%); treatment-related AEs with highest frequency were vomiting and dizziness (both n=4/44; 9.1%). 7 AEs led to discontinuation in 4 pts; 5 AEs were considered osilodrostat related (nausea and vomiting in 1 pt; worsening hypertension, uncontrolled blood pressure and dizziness in another) and 2 were not (pituitary tumor surgery and right adrenalectomy). AEs related to hypocortisolism, accumulation of adrenal hormone precursors, QT prolongation and pituitary tumor enlargement occurred in 7 (7.4%), 4 (4.3%), 2 (2.1%) and 0 pts, respectively. At month 3, mUFC, serum cortisol and LNSC were normalized in 71.4% (n=10/14), 69.2% (n=18/26) and 50.0% (n=7/14) of pts. Conclusions: Results from this real-world clinical setting show that osilodrostat is generally well tolerated and provides early improvements in mUFC and LNSC in pts with endogenous CS, building on evidence from the previous randomized, controlled trials LINC 3 and LINC 4. Presentation: 6/3/2024

6372 Changes in Blood Steroid Hormone Profile after Switching from Metyrapone to Osilodrostat

Abstract Disclosure: K. Yokozeki: None. H. Kameda: None. A. Miya: None. H. Nomoto: None. A. Nakamura: None. S. Jin: None. K. Matoba: None. T. Atsumi: None. Background: The new steroidogenesis inhibitor osilodrostat has recently been approved for use in Cushing's syndrome. However, there are limited studies on changes in blood steroid hormone profiles after switching from existing drugs including metyrapone. Purpose: To study the changes in steroid hormone profiles with switching from metyrapone to osilodrostat in patients with Cushing's disease and to examine the differences in clinical efficacy. Case 1: A woman in her 40s underwent transsphenoidal pituitary tumor surgery (TSS) for Cushing's disease in X-12, but was not in remission and was treated with 1000 mg/day of metyrapone and oral hydrocortisone. In X-3, the patient complained of masculinization and was started pasireotide LAR 10 mg per month, which was subsequently increased to 30 mg. Despite the addition of 240 mg/day of trilostane in X-2, the patient did not show improvement. Switched the steroidogenesis inhibitors to osilodrostat 4 mg/day in year X, blood cortisol and testosterone levels decreased and the symptoms of virilization disappeared.Case 2: A woman in her 40s experienced edema in her face and limbs, increased appetite and weight gain since Y-13. After endocrinological examination, she was diagnosed with Cushing's disease. TSS was performed and she was in remission. However, she suffered a relapse in Y-4 and was started on metyrapone, which was titrated up to 4,000 mg/day. Due to gastric discomfort, metyrapone was switched to osilodrostat 52 mg/day in year Y, leading to an improvement of her gastric symptoms and stabilized blood cortisol level. Case 3: A woman in her 70s underwent TSS for Cushing's disease in Z-6, but the tumor remained and she was prescribed metyrapone 1,500 mg/day. The disease was stable and complications were under control with metyrapone. In Z-1, the patient developed elevated blood pressure and worsening leg edema, and metyrapone was switched to osilodrostat 3 mg/day in year Z, resulting decreased blood cortisol level and blood pressure. Results: Liquid chromatograph mass spectrometry (LC-MS) analysis of blood steroid hormone profiles in above three cases demonstrated a decrease in 17-OH pregnenolone, 17-OH progesterone, and 11-deoxycorticosterone after switching the steroidogenesis inhibitors. Discussion and Conclusion: It has been noted that osilodrostat lowers serum cortisol in a shorter period of time compared to metyrapone and may also decrease the number of antihypertensive medications used. Under metyrapone administration, hypertrichosis, hypertension, and hypokalemia are often observed with increased mineralocorticoid precursors, but osilodrostat may have a different clinical effect as a result of its different pattern of steroid hormone synthase inhibition. Presentation: 6/2/2024

Multi-center study on sellar reconstruction after endoscopic transsphenoidal pituitary surgery.

Surgical techniques for sellar reconstruction include no reconstruction, use of synthetic materials, autologous grafts, and/or vascularized flaps. The aim of this study was to conduct a multi-center study comparing the efficacy and postoperative morbidity associated with different sellar reconstruction techniques. A retrospective chart review of patients who underwent endoscopic transsphenoidal surgery for pituitary tumors from five participating sites between January 2021 and March 2023 was performed. The variables included demographics, tumor characteristics, reconstruction technique, postoperative cerebrospinal fluid leak (CSF) leak, and 22-item Sino-Nasal Outcome Test (SNOT-22) scores. Comparisons of postoperative complications, SNOT-22 scores, and duration of surgery by type of onlay reconstruction were evaluated using Fisher's exact test, analysis of variance, and Kruskal‒Wallis test. Five hundred and one patients were identified. The median tumor size was 2.1cm, and 64% were non-functioning. Intraoperative CSF leak was identified in 38% of patients. A total of 89% of patients underwent onlay reconstruction: 49% were reconstructed with mucosal grafts, 35% with nasoseptal flaps, and 5% with other onlay techniques. Nasoseptal flaps were utilized more frequently in the setting of giant pituitary adenomas (>3cm), medial cavernous sinus wall resection, and high-flow intraoperative CSF leaks. Cases who utilized mucosal grafts had an overall shorter operating time (median: 183 min vs. 240 min; p<0.001). Five postoperative CSF leaks were identified, and therefore, statistical analysis could not be performed for this complication. The effectiveness and morbidity of different sellar reconstruction techniques are comparable. Vascularized flaps were utilized more frequently in the setting of larger tumors and high-flow intraoperative CSF leaks.

Fertility outcomes following transsphenoidal surgery for pituitary tumours at the university hospital of wales, cardiff

Fertility outcomes following transsphenoidal surgery for pituitary tumours at the university hospital of wales, cardiff

Clinical observation of 7 cases of functional pituitary neuroendocrine tumor treated by endoscopic transnasal selective resection of the cavernous sinus medial wall

The clinical data of 7 patients (3 males and 4 females) with functional pituitary neuroendocrine tumor treated by endoscopic transnasal resection of the cavernous sinus medial wall from May to October 2023 in the Department of Neurosurgery of the First Affiliated Hospital of University of Science and Technology of China were retrospectively analyzed. They ranged in age from 29 to 60, with an average age of 45. The clinical diagnosis was acromegaly in 5 cases and Cushing's disease in 2 cases. There were 1 cases of microadenoma and 6 cases of macroadenoma. Knosp grade: Grade 1 adenoma in 3 cases, grade 2 adenoma in 3 cases and grade 3A adenoma in 1 case. Intraoperative resection of cavernous sinus medial wall was performed on the side of tumor. Five cases were determined to be invaded by tumor, and 2 cases were uncertain. No internal carotid artery injury occurred in all patients. The average intraoperative blood loss was 156 ml, and no patient was transfused. Postoperative endocrine remission was found in 6 cases, and tumor cells were found in 6 cases by pathological examination of the medial wall of cavernous sinus. No serious complications occurred in all patients. For Knosp grade 1-3 functional pituitary neuroendocrine tumor surgery, if there is no clear false envelope or normal pituitary between the tumor and the cavernous sinus medial wall during the operation, the cavernous sinus medial wall should be actively removed to improve the postoperative endocrine remission rate.

No unfavorable effects on the menstruation recovery of early postoperative hypoprolactinemia after transsphenoidal surgery in patients with lactotroph pituitary neuroendocrine tumor

ObjectiveTranssphenoidal surgery for lactotroph pituitary neuroendocrine tumor (PitNET) lowers serum prolactin concentrations, occasionally below the normal range. However, the clinical significance of postoperative hypoprolactinemia is still unclear. In this study, we retrospectively reviewed the female patients with lactotroph PitNET who were treated with transsphenoidal surgery to elucidate the influence of postoperative hypoprolactinemia on regular menstruation restoration and endocrinological remission.ResultsThe serum prolactin levels in all thirty three participating females had decreased following surgery. Serum prolactin levels in seven patients had decreased below the lower limit of normal ranges (hypoproactinemia group) and in the remaining twenty six patients, it was within the normal range (non-hypoproractinemia group). In hypoprolactinemia group, regular menstruation was restored in all patients with only lactotroph axis deficiency. Nine patients from the non-hypoprolactinemia group experienced re-elevation of serum prolactin concentration (27%). No patient in hypoprolactinemia group experienced the relapse of hyperprolactinemia. These data suggest that early postoperative hypoprolactinemia after transsphenoidal surgery for lactotroph PitNET is not only a good predictive factor for endocrinological remission but also no unfavorable effects on regular menstruation restoration.

Endoscopic and exoscopic surgery for brain tumors.

Nerves and blood vessels must be protected during brain tumor surgery, which has traditionally relied on microscopes. In the 2000s, endoscopes and related equipment were developed for neurosurgery. In this review, we aim to outline the role of endoscopes in brain tumor surgery and discuss the emerging use of exoscopes. The primary use of endoscopes in brain tumor surgery is in endoscopic endonasal surgery for pituitary tumors. By using the space within the sphenoid sinus, surgeons can insert an endoscope and instruments such as forceps or scissors through the nose to access and remove the tumor. Compared to microscopes, endoscopes can get closer to tumors, nerves, and blood vessels. They enable wide-angle observation of the skull base, making them valuable for skull base tumors as well as pituitary tumors. Endoscopes are also used in cases where a brain tumor is associated with hydrocephalus, allowing surgeons to correct obstructive hydrocephalus and perform tumor biopsies simultaneously. Exoscopy, a newer technique introduced in recent years, involves surgeons wearing special glasses and removing the tumor while viewing a three-dimensional monitor. This approach reduces surgeon fatigue and allows for more natural positioning during lengthy brain tumor surgeries. Future brain tumor surgeries will likely involve robotic surgery, which is already used for other organs. This is expected to make brain tumor removal safer and more accurate.

Comparison of Response First Technique with Reversal First Technique for Quality of Extubation in Patients Undergoing Transsphenoidal Pituitary Surgery: A Randomized Clinical Trial.

Early and smooth extubation following anesthesia is an important concern in patients undergoing transsphenoidal pituitary surgery to permit early neurological evaluation and prevent complications. The aim was to compare the RESPONSE FIRST and REVERSAL FIRST techniques for quality of extubation (QOE) in patients undergoing endoscopic transsphenoidal pituitary surgery. Fifty-six patients aged 18-60 years, with American Society of Anesthesiologists Physical Statuses I-II, and undergoing transsphenoidal surgery for pituitary tumors were randomized into either the RESPONSE FIRST group, in which neuromuscular reversal was given following the patient's response to oral commands, or the REVERSAL FIRST group, in which reversal of neuromuscular blockade (NMB) was given at the return of spontaneous respiration. QOE was the primary outcome. Hemodynamic response, jugular venous oxygen saturation (SjVO2), time to extubation, and awareness during emergence were assessed as secondary outcomes. The QOE in the RESPONSE FIRST group was significantly better than the REVERSAL FIRST group (mean (interquartile range (IQR)), 18 (17-19) vs 14 (12-14.75), P < 0.001). Heart rate (HR) and mean arterial pressure (MAP) were better in the RESPONSE FIRST group when compared to the REVERSAL FIRST group at the time of extubation, at 5 minutes, and 15 minutes following extubation (P < 0.05). SjVO2values were higher in the REVERSAL FIRST group as compared to the RESPONSE FIRST group during extubation and at 5 minutes after extubation (P < 0.01). There was no significant difference in the time to extubation between the groups (P = 0.73). The RESPONSE FIRST technique is associated with better QOE and preservation of systemic and cerebral hemodynamics during extubation in patients undergoing transsphenoidal pituitary surgery when compared to the REVERSAL FIRST technique.

The effect of preoperative TSH levels on perioperative complications in patients undergoing pituitary surgery

IntroductionPituitary surgery involves special conditions for the anaesthetist due to the anatomical localisation and the role of the pituitary gland in hormonal balance. The aim of this study was to retrospectively investigate the effect of TSH levels on perioperative complication rates in patients undergoing pituitary surgery.MethodsIn this study, patients who underwent pituitary surgery at Izmir Katip Celebi University Ataturk Training and Research Hospital between January 2017 and November 2022 were retrospectively screened. Two patients out of the 137 were excluded from the study as they underwent simultaneous aneurysm surgery along with pituitary tumor surgery. A total of 135 patients meeting the criteria were analyzed. Patients were divided into three groups according to TSH levels. Perioperative complication rates and mortality rates were compared between the three groups.FindingsThe study included a total of 135 patients, with an age range of 16–76 years. Among the groups with low–normal–high TSH levels, there were no statistically significant difference observed, in postoperative complications, such as epistaxis, rhinorrhea, postoperative nausea/vomiting, seizures, hypertension, and hypotension. When looking at the incidence of postoperative diabetes insipidus, a significant difference was found between the groups. When examining the mortality rates on the 28th day, a significant difference was found between the groups, with a mortality rate of 25% in the high TSH group (p < 0.5).ConclusionsThe risk of perioperative mortality is higher in patients with TSH levels above normal.

Risk Factors for Isolated Sphenoid Sinusitis after Endoscopic Endonasal Transsphenoidal Pituitary Surgery.

(1) Background: Transsphenoidal pituitary surgery can be conducted via microscopic or endoscopic approaches, and there has been a growing preference for the latter in recent years. However, the occurrence of rare complications such as postoperative sinusitis remains inadequately documented in the existing literature. (2) Methods: To address this gap, we conducted a comprehensive retrospective analysis of medical records spanning from 2018 to 2023, focusing on patients who underwent transsphenoidal surgery for pituitary neuroendocrine tumors (formerly called pituitary adenoma). Our study encompassed detailed evaluations of pituitary function and MRI imaging pre- and postsurgery, supplemented by transnasal endoscopic follow-up assessments at the otolaryngology outpatient department. Risk factors for sinusitis were compared using univariate and multivariate logistic regression analyses. (3) Results: Out of the 203 patients included in our analysis, a subset of 17 individuals developed isolated sphenoid sinusitis within three months postoperation. Further scrutiny of the data revealed significant associations between certain factors and the occurrence of postoperative sphenoid sinusitis. Specifically, the classification of the primary tumor emerged as a notable risk factor, with patients exhibiting nonfunctioning pituitary neuroendocrine tumors with 3.71 times the odds of developing sinusitis compared to other tumor types. Additionally, postoperative cortisol levels demonstrated a significant inverse relationship, with lower cortisol levels correlating with an increased risk of sphenoid sinusitis postsurgery. (4) Conclusions: In conclusion, our findings underscore the importance of considering tumor classification and postoperative cortisol levels as potential predictors of postoperative sinusitis in patients undergoing transsphenoidal endoscopic pituitary surgery. These insights offer valuable guidance for clinicians in identifying at-risk individuals and implementing tailored preventive and management strategies to mitigate the occurrence and impact of sinusitis complications in this patient population.

Correlation between tumor invasion and somatostatin receptor subtypes in acromegaly.

The low expression of somatostatin receptor (SSTR) subtypes in somatotropinoma is associated with a poor response to somatostatin analogs (SSAs). However, the correlation between SSTRs and tumor invasion has not yet been clarified. Therefore, the authors aimed to investigate the relationship between SSTRs and tumor invasion, as well as the correlation between tumor invasiveness and pharmacological response to SSAs. A total of 102 patients with acromegaly who underwent surgery between December 2016 and December 2021 at the largest pituitary tumor surgery center in southern China were included in this retrospective study. Patients were divided into the noninvasive tumor group (Knosp grades 0-2 and Hardy-Wilson grade I or II) and invasive group (either Knosp grade 3 or 4 or Hardy-Wilson grade III or IV). The positive response to SSAs was defined by the following criteria after at least 3 months of SSA treatment: 1) ≥ 50% reduction or age- and sex-adjusted normal range of insulin-like growth factor-1 (IGF-1) level; 2) ≥ 80% reduction in or normal range of growth hormone (GH) level; or 3) > 20% reduction in tumor volume. The reference for the normal range of age- and sex-adjusted serum IGF-1 levels was derived from a survey of 2791 healthy adults (1339 males and 1452 females) in China. Demographics and clinical characteristics including tumor size, biochemical assessment, expression levels of SSTRs, and response to preoperative SSAs were compared between the invasive group and noninvasive group. Receiver operating characteristic (ROC) curve analysis was performed to assess the association between SSTR2 and tumor invasion. Compared with the noninvasive group, the invasive group presented with a larger tumor size (9.99 ± 10.41 cm3 vs 3.50 ± 4.02 cm3, p < 0.001), relatively lower SSTR2 expression (p < 0.001), and poorer response to SSAs (36.4% vs 91.7%, p < 0.001). In addition, there was a significant negative correlation between SSTR2 mRNA level and tumor size (r = -0.214, p = 0.031). However, there were no statistically significant differences in the expression of SSTR1, SSTR3, and SSTR5 between the groups. ROC analysis revealed that the low SSTR2 mRNA level was closely associated with tumor invasion (area under the curve 0.805, p < 0.0001). Tumor invasion is negatively correlated with SSTR2 level but is not associated with other SSTR subtypes. Patients with invasive tumors have a poorer response to SSA therapy, which may be due to the low level of SSTR2 expression. Therefore, SSTR2 could be considered as a routine investigative marker for aiding management of postoperative residual tumors.

Clinical application of reserved gastric tube in neuroendoscopic endonasal surgery for pituitary tumor.

The neuroendoscopic approach has the advantages of a clear operative field, convenient tumor removal, and less damage, and is the development direction of modern neurosurgery. At present, transnasal surgery for sphenoidal pituitary tumor is widely used. But it has been found in clinical practice that some patients with this type of surgery may experience post-operative nausea and vomiting and other discomforts. To explore the effect of reserved gastric tube application in the neuroendoscopic endonasal resection of pituitary tumors. A total of 60 patients who underwent pituitary adenoma resection via the endoscopic endonasal approach were selected and randomly divided into the experimental and control groups, with 30 in each group. Experimental group: After anesthesia, a gastric tube was placed through the mouth under direct vision using a visual laryngoscope, and the fluid accumulated in the oropharynx was suctioned intermittently with low negative pressure throughout the whole process after nasal disinfection, during the operation, and when the patient recovered from anesthesia. Control group: Given the routine intraoperative care, no gastric tube was left. The number of cases of nausea/vomiting/aspiration within 24 h post-operation was counted and compared between the two groups; the scores of pharyngalgia after waking up, 6 h post-operation, and 24 h post-operation. The frequency of postoperative cerebrospinal fluid leakage and intracranial infection were compared. The hospitalization days of the two groups were statistically compared. The times of postoperative nausea and vomiting in the experimental group were lower than that in the control group, and the difference in the incidence of nausea was statistically significant (P < 0.05). After the patient woke up, the scores of sore throat 6 h after the operation and 24 h after operation were lower than those in the control group, and the difference was statistically significant (P < 0.05). The number of cases of postoperative cerebrospinal fluid leakage and intracranial infection was higher than that of the control group, but there was no statistically significant difference from the control group (P > 0.05). The hospitalization days of the experimental group was lower than that of the control group, and the difference was statistically significant (P < 0.05). Reserving a gastric tube in the endoscopic endonasal resection of pituitary tumors, combined with intraoperative and postoperative gastrointestinal decompression, can effectively reduce the incidence of nausea, reduce the number of vomiting and aspiration in patients, and reduce the complications of sore throat The incidence rate shortened the hospitalization days of the patients.

Visual outcomes and optimal timing for repeat surgery in cases of postoperative hematoma following transsphenoidal surgery for pituitary neuroendocrine tumors: A retrospective cohort study.

To investigate the visual outcomes and optimal timing for repeat surgery in cases of postoperative hematoma following transsphenoidal surgery for pituitary neuroendocrine tumors (PitNETs). A retrospective study was conducted on 28 patients who developed evident postoperative hematoma out of a total of 9,010 patients. The hematomas were classified into three types based on their CT appearance. Type 1a - mild high density with no tension, Type 1b - thin-layer high density; Type 2a - solid high density with large empty cavities, Type 2b - solid high density with small empty cavities; Type 3 -solid high density with no cavity showing high tension. Patient data were collected for analysis. The study cohort comprised 10 female and 18 male patients, with a mean age of 51.5±11.9 years. Most patients presented with large adenomas (median diameter 36mm). Postoperative visual sight improved in 12 patients, remained stable in 11 patients, and worsened in 5 patients. Notably, no patients experienced worsened visual sight beyond twenty-four hours after the operation. Among the five patients with visual deterioration, four had CT type 3 hematoma (4/6, 66.7%), and one had CT type 2b hematoma (1/9, 11.1%). Patients in the type 3 CT group were significantly more prone to experience visual deterioration compared to those in the type 2 group (odds ratio [OR] 2.154 [95% CI 1.858-611.014], P=.027). Four patients underwent repeat surgery after visual deterioration, resulting in visual improvement following a prolonged recovery period. Postoperative hematoma had limited impact on pituitary dysfunction and hyponatremia. Our study reveals a significant association between postoperative hematoma CT types and visual deterioration. For patients with stable visual sight and type 1 or 2a hematoma, conservative strategies may be considered. Conversely, type 2b and 3 patients are at higher risk of visual deterioration, especially within the first 24 hours after the operation. Consequently, early reoperation before vision worsens may be a prudent approach to reduce risks and improve visual outcomes, particularly in type 3 patients.

The impact of surgeon's academic leave on surgical outcomes for endoscopic transsphenoidal resection of pituitary tumors.

Endoscopic surgery has become the mainstay of pituitary surgery, but requires comprehensive surgical training. We evaluate the impact of a surgeon's academic leave during endoscopic training on surgical outcomes of patients with pituitary tumors. This retrospective study reviewed the surgical outcomes of endoscopic transsphenoidal surgery for pituitary tumors performed by a single surgeon. The last 56 surgical cases were performed between July 2010 and August 2014 before academic leave (Phase 1 surgery group), while another 56 consecutive cases were performed between November 2017 and March 2020 immediately after the surgeon's academic leave (Phase 2 surgery group). Demographic and clinical characteristics were collected and compared between the two surgery groups. Overall, most surgical outcomes of endoscopic transsphenoidal surgery were not affected adversely by the period of academic leave. The operative time and length of hospital stay was lower in the Phase 2 surgery group compared to the Phase 1 surgery group (P<0.05). Postoperative tumor residual, intraoperative cerebrospinal fluid (CSF) leaks and reoperation also decreased significantly in the Phase 2 group compared to the Phase 1 group (P<0.05). Similar results were observed in patients operated using a one-hand/mono-nostril and two-hand/one-and-half nostril technique. Academic leave had no negative impact on most surgical outcomes for endoscopic transsphenoidal resection of pituitary tumors. Moreover, a trend toward shorter operative times and length of hospital stays was noted for patients receiving surgery immediately after surgeon's return from leave.

Intrasellar Arachnoid Diverticulae as a Risk Factor for Intraoperative Cerebrospinal Fluid Leakage in Patients Undergoing Endoscopic Transsphenoidal Surgery.

Intrasellar arachnoid diverticulae can often be identified on preoperative imaging in patients undergoing endoscopic transsphenoidal surgery. The objective of this study was to characterize arachnoid diverticulae both qualitatively and quantitatively in a large institutional cohort of patients with pituitary tumors and to evaluate its association with intraoperative cerebrospinal fluid (CSF) leak. Preoperative imaging studies of 530 patients who underwent primary endoscopic transsphenoidal resection of pituitary tumors were examined both quantitatively and qualitatively for the presence of an intrasellar arachnoid diverticulum. A matched cohort analysis was performed to compare patients with a "significant" (>50% sellar depth) diverticulum with those with nonsignificant/no diverticulum. Morphologically, diverticulae were separately classified as Type 1 (ventral CSF cleft with no tumor/gland tissue between sellar face and infundibulum) or Type 2 (central CSF cleft with tumor/gland tissue between sellar face and infundibulum). Arachnoid diverticulae were noted in 40.2% of cases, and diverticulum depth was linearly correlated with tumor size and body mass index. A significant diverticulum was identified in 66 cases (12.5%) and was significantly associated with the functional tumor subtype ( P = .005) and intraoperative CSF leak ( P < .001). Type 1 clefts were associated with nonfunctional pathology ( P = .034) and the presence of suprasellar extension ( P = .035) and tended to be deeper than Type 2 clefts ( P < .001), with a higher incidence of intraoperative CSF leak ( P = .093). On logistic regression analysis, only the presence of a significant diverticulum was independently associated with intraoperative CSF leak (odds ratio 4.545; 95% CI 2.418-8.544; P < .001). The presence of an intrasellar arachnoid diverticulum should alert the surgeon to an elevated risk of intraoperative CSF leak during transsphenoidal surgery for pituitary tumors. A relatively limited surgical exposure tailored to the craniocaudal extent of the sellar pathology should be considered in these patients.

If you let it fall, you can save it all: Preventing permanent Diabetes mellitus in pituitary tumor surgery

If you let it fall, you can save it all: Preventing permanent Diabetes mellitus in pituitary tumor surgery

A prospective-randomized placebo-controlled trial comparing the effects of nebulized dexmedetomidine v/s dexmedetomidine-lignocaine mixture on intraoperative hemodynamics and surgical field quality in patients undergoing endoscopic transnasal transsphenoidal pituitary tumor surgery

Background: During transnasal transsphenoidal pituitary surgery (TNTSS), the primary objective is to maintain stable hemodynamics while ensuring ideal surgical conditions. This study aimed to investigate the effect of nebulized dexmedetomidine on hemodynamic parameters and the quality of the surgical field during TNTSS. Methods: Seventy-five patients scheduled for TNTSS were randomized into three groups of 25 each and received preoperative nebulization with 5 mL of nebulizing fluid consisting of 1.5 μg/kg of dexmedetomidine with saline in dexmedetomidine (D) group; 1.5 μg/kg of dexmedetomidine with 2% lignocaine in dexmedetomidine-lignocaine (DL) group and normal saline in the control (S) group. Heart rate (HR), mean blood pressure, Formmers score, anesthetic requirement, and emergence were evaluated for each group. Results: Group S had significantly higher HR and mean arterial pressure than the other two groups across various time points during surgery (P &lt; 0.01). The total requirements for fentanyl, propofol, sevoflurane, and labetalol and the incidence of delayed emergence were significantly higher in the S group compared to the other two groups (P &lt; 0.01). The D and DL groups exhibited significantly better surgical field conditions than the S group. In all the parameters assessed, patients in the D group outperformed those in the DL group. Conclusion: The administration of nebulized dexmedetomidine, both alone and in combination with lignocaine, resulted in stable hemodynamics, favorable operative conditions, reduced anesthetic requirement, and facilitated prompt emergence during TNTSS. Nebulized dexmedetomidine proved superior to its combination with lignocaine across all evaluated parameters.

Asymmetric Janus fiber membrane for preventing cerebrospinal fluid leakage and promoting bone regeneration

Repairing skull base defects caused by pituitary tumor surgery remains challenging as it is difficult to restore its structural integrity and avoid cerebrospinal fluid leakage. To address this issue, this study aimed to prepare a Janus bilayer membrane with asymmetric wetting properties (hydrophobicity/super hydrophilicity) using polycaprolactone (PCL), gelatin (Gel), and polydopamine (PDA) through a layer-by-layer electrospinning technique. Randomly stacked hydrophobic PCL fibers were designed as the upper layer to control leakage of cerebrospinal fluid. Meanwhile, the bottom layer composed of hydrophilic PG-PDA nanofibers was utilized to promote the skull base bone repair. The experimental results showed that under a pressure of 200 mm water column, the Janus bilayer membrane could efficiently prevent leakage for several days. The prepared Janus PCL/PG-PDA membrane revealed excellent mechanical properties to mimic bone ECM and showed surface bioactivity to accelerate mineralization. The results of in vitro cell experiments indicated that the Janus membrane prepared in this study displays exceptional biocompatibility, with the PCL/PG-0.5%PDA fiber membrane demonstrating the highest capacity to promote osteogenic differentiation. These observations suggest that the asymmetric Janus fiber membrane (PCL/PG-PDA) has the potential to serve as a promising candidate for skull base repair.

SAT625 The EGF-TBX19-EGFR Positive Feedback Loop Regulates The Expression Of The CD44v9/SLC7A11 Antioxidant System Within Corticotroph Pituitary Neuroendocrine Tumors

Abstract Disclosure: J. Chakrabarti: None. J. Eschbacher: None. K. Yuen: None. A.S. Little: None. Y. Zavros: None. Background: Stereotactic radiosurgery is a therapeutic modality considered in the adjuvant setting of patients with failed transsphenoidal surgery or recurrence of corticotroph pituitary neuroendocrine tumors (PitNETs), with variable biological remission rates ranging between 17% and 87%. Generated by alternative mRNA splicing (CD44v), CD44v9 is expressed in cancer stem cells and promotes resistance to reactive oxygen species (ROS) through the stabilization of the SLC7A11 (xCT) cystine glutamate transporter, but the role of this antioxidant system in PitNETs is unknown. TBX19 belongs to the T subfamily of TBX genes and is known to promote cancer cell metastasis. TBX19 is expressed within the pituitary gland and acts as a component of the proopiomelanocortin (POMC) gene activation program that works as a transcriptional activator. Epidermal Growth Factor Receptor (EGFR) via binding to its ligand Epidermal Growth Factor (EGF) signals to upregulate TBX19 expression via the ERK/NF-κB pathway. Within the pituitary, EGFR and its downstream pathway components (AKT, mTORC) are significantly increased in corticotroph PitNETs are associated with elevated ACTH secretion. Hypothesis: EGF/EGFR induces an EGF-TBX19-EGFR positive feedback loop that subsequently leads to the expression of the CD44v9/SLC7A11 antioxidant system within radiation-therapy resistant SOX2+ corticotroph PitNET cells. Methods: Human PitNET tissue was harvested during transsphenoidal pituitary surgery from CD patients to generate organoids (PitNETorg). Patient hPitNETsorg were pretreated with either Vandetanib (Vand), Rapamycin (Rapa, mTOR inhibitor), Erastin (xCT inhibitor), Mifepristone (Mife, glucocorticoid inhibitor) or Cabergoline (Caber, D2 receptor inhibitor) prior to 0, 4, 8 and 16Gy radiation doses. Functional analyses will be performed by spectral flow cytometry (Cytek™ Aurora), hormone secretion and high content confocal microscopy. Results: Decreased expression of CD44v9 and xCT correlated with increased apoptosis in hPitNETorg cultures in response to Vand, Rapa, and Erastin when compared to Veh, Mife and Caber pretreatments at an optimal radiation dose of 8Gy. Pretreatment of hPitNETorg with Rapa resulted in decreased expression CD44v9, a response mediated by of HIF-1α. Inhibition of TBX19 using a MEK inhibitor resulted in decreased expression of EGFR and downstream signaling components AKT and mTORC that correlated with decreased ACTH hPitNETorg secretion. Conclusions: The EGF-TBX19-EGFR positive feedback loop regulates CD44v9/xCT resistance to radiation therapy. Therefore, pretreatment of CD patients with drugs targeting the CD44v9/xCT antioxidant system may increase the efficacy, shorten latency time to remission, and decrease toxicity of stereotactic radiosurgery for the treatment of residual or recurrent functional corticotroph PitNETs. Presentation: Saturday, June 17, 2023

Endoscopic Reconstruction of the Sellar Floor by Extended Inferior Turbinate Flap in Recurrent Pituitary Tumors.

Objective This aim of this study was to address the outcome of endoscopic reconstruction of the sellar floor by extended inferior turbinate flap. Patients and Methods This is a retrospective study of 34 patients with a recurrent pituitary tumor. They were treated between March 2018 and December 2021 by endoscopic extended endonasal approach with the reconstruction of the sellar floor by an extended posterior pedicle inferior turbinate flap. The clinical and radiological follow-up was performed immediately postoperation and regularly every 3 months up to 1 year, and the available data from the last follow-up visit were included in the analysis. Results The patients' age ranged between 40 and 65 years, with a slight female predominance (55.9%). Headache was the main presentation (47.1%), and functional tumors were found in 50.0% patients. Visual disturbances were field defects among 61.8% and papilledema among 52.9% patients. Preoperative endoscopy revealed postseptectomy as the significant finding (73.5%), followed by postseptectomy and adhesion (14.7%) and finally postseptectomy and hypertrophied inferior turbinate (11.8%). Total tumor resection was achieved in 76.5%, visual improvement was recorded in 52.9%, and no complications were reported in 82.4% patients. Cerebrospinal fluid (CSF) leak was not reported in any of the studied patients. Finally, total resection was significantly associated with younger age, non-functioning tumor and improvement of headache. Conclusion The extended inferior turbinate flap is an effective and safe approach for sellar floor reconstruction in endoscopic endonasal surgery for recurrent pituitary tumors. The extension overcomes the relatively small inferior flap and its limited arc of rotation.