Knosp Classification Research Articles

Simultaneous combined keyhole mini-transcranial approach and endoscopic transsphenoidal approach to remove multi-lobulated pituitary neuroendocrine tumor with suprasellar extension

BackgroundTranssphenoidal surgery (TSS) is the main method to remove pituitary neuroendocrine tumor (PitNET), but large or multi-lobulated one is still challenging. ObjectiveThe less invasive simultaneous combined keyhole mini-transcranial approach and standard transsphenoidal approach was used to remove multi-lobulated or hourglass-shaped non-functioning PitNET to avoid the specific complications related to extended TSS. MethodsTwenty-one patients of large multi-lobulated or hourglass-shaped PitNET (6 patients were recurrent cases after TSS or transcranial approach) were treated by this simultaneous combined approach. The supraorbital or midline keyhole approach was performed under the operating microscope so that the fine arteries feeding optic apparatus were dissected from the tumor capsule safely and securely and the suprasellar part of the tumor was removed in the extra-capsular fashion in combination with transsphenoidal approach. ResultsVisual function improved after the surgery in 14 (74 %) of 19 patients with preoperative disturbance of the visual fields. Four patients (19 %) developed postoperative deterioration of pituitary endocrine functions requiring permanent hormonal replacement. One patient (4.2 %) suffered cortical laminar necrosis without permanent disorders and another patient (4.2 %) suffered cerebrospinal fluid rhinorrhea but neither was permanent. Postoperative computed tomography detected no subarachnoid hemorrhage in any patient. Gross total removal was achieved in 15 patients (71 %). Five patients (24 %) with subtotal removal and one patient (4.2 %) with partial removal had lateral tumor extension with Knosp classification 3 or 4. ConclusionThe combined method is an effective treatment option to remove complex PitNET safely and securely with dissecting fine arteries on the tumor capsule.

Comparative analysis of intraoperative and imaging features of invasive growth in pituitary adenomas.

Most pituitary adenomas (PAs), also termed pituitary neuroendocrine tumors, are benign in nature and can be treated effectively by surgical resection, medical treatment, and in special cases by radiotherapy. However, invasive growth can be an important feature of a more aggressive behavior and adverse prognosis. The extension of PAs into the cavernous sinus can be categorized according to the Knosp criteria on magnetic resonance imaging (MRI). Comparative analyses of MRI features and intraoperative findings of invasive growth regarding different clinical factors are still scarce. We performed a retrospective single-center analysis of 764 PAs that were surgically treated between October 2004 and April 2018. Invasive growth was assessed according to the surgical reports and preoperative MRI (Knosp criteria). Clinical data, such as patient age at diagnosis and gender, histopathological adenoma type, and extent of resection, were collected. Invasive features on MRI were seen in 24.4% (Knosp grades 3A-4, 186/764) of the cases. Intraoperatively, invasion was present in 42.4% (324/764). Complete resection was achieved in 80.0% of adenomas and subtotal resection, in 20.1%. By multivariate analysis, invasion according to intraoperative findings was associated with the sparsely granulated corticotroph (SGCA, P = .0026) and sparsely granulated somatotroph (SGSA, P = .0103) adenoma type as well as age (P = .0287). Radiographic invasion according to Knosp grades 3A-4 correlated with age (P = .0098), SGCAs (P = .0005), SGSAs (P = .0351), and gonadotroph adenomas (P = .0478). Both criteria of invasion correlated with subtotal resection (P = .0001, respectively). Both intraoperative and radiographic signs of invasive growth are high-risk lesions for incomplete extent of resection and occur more frequently in older patients. A particularly high prevalence of invasion can be found in the SGCA and SGSA types. Cavernous sinus invasion is also more common in gonadotroph adenomas. Usage of the Knosp classification is a valuable preoperative estimation tool.

202 The Role of Surgical Management for Prolactinoma in the Era of Dopaminergic Agonists: An International Multicenter Report

INTRODUCTION: Although first-line prolactinoma (PL) management typically involves dopamine agonists (DAs), the role of surgery as a primary therapeutic is being reconsidered given the undesirable side effects of long-term DAs. METHODS: Patients surgically treated for PL from January 2017 through December 2020 were identified. Preoperative characteristics and postoperative outcomes were assessed. Multivariate models adjusting for tumor characteristics and surgery complexity identified factors predictive of complications and long-term adverse outcomes. RESULTS: Among 272 patients identified (65.1% female), the mean age was 38.0 ± 14.3 years. Overall, 54.4% of PLs were macroadenomas. Most PLs were managed microscopically (69.9%) and fewer endoscopically (29.0%). Although 29.8% of patients experienced at least one early postoperative complication, most were minor (39.3%), with less being major complications (4.4%). The most common major complications were epistaxis and worsened vision. Most minor complications involved electrolyte/sodium dysregulation. Based on available data on follow-up, disease remission on long-term follow-up imaging was achieved in 94.8% of cases, and residual/recurrent tumor was seen in 19.3%. Reoperations were required for 2.9% of cases. Upon multivariate analysis, previous surgery was significantly predictive of intraoperative complications (6.14 OR, p < 0.01) and major complications (14.12 OR, p < 0.01). Previous pharmacotherapy (0.27 OR, p = 0.02) and cavernous sinus invasion (0.19 OR, p = 0.03) were significantly prohibitive against long-term endocrinological cure. Knosp classification was highly predictive of residual tumor or PL recurrence on 6-month follow-up imaging (4.60 OR, p < 0.01). CONCLUSIONS: Our results evaluate a modern, multicenter, global series of patients treated for PL. This data serves as a benchmark to compare with DAs and demonstrates that surgery offers high rates of remission with low rates of complications and recurrence. It may be reasonable to consider surgery as an alternative to DAs.

504 Anterior-posterior Diameter Is a Key Driver of Resectability and Complications for Pituitary Adenomas With Suprasellar Extension in Endoscopic Transsphenoidal Surgery

INTRODUCTION: As endoscopic transsphenoidal approaches are more routinely selected for larger pituitary adenomas with parasellar extension, understanding potential anatomical factors that limit resection and contribute to complications becomes increasingly important. METHODS: A single-center retrospective review of all endoscopic transsphenoidal surgeries for pituitary adenomas with suprasellar extension from 2015-2020 was performed. Preoperative MRIs were systematically assessed to assign a Knosp classification, a Zurich Pituitary Score (ZPS), and to measure lesional suprasellar dimensions. Univariate comparisons and multivariate regression models were employed to assess the influence of these factors on extent of resection (EOR) and postoperative complications. RESULTS: Of the 96 patients with suprasellar pituitary adenomas who underwent endoscopic transsphenoidal surgery, 74 patients (77%) had a gross total resection (GTR). Neither Knosp grade nor ZPS were associated with GTR (Knosp 3A-4 versus Knosp 0-2, p = 0.069; ZPS III-IV versus ZPS I-II, p = 0.079). Multivariate regression identified suprasellar anterior-posterior tumor diameter (SSAP) as the only significant predictor of EOR (OR 0.951, 95% CI 0.905-1.000, p = 0.048*). Higher SSAP also showed the strongest association with an increased overall complication rate (p = 0.0003*) and intraoperative CSF leaks (p = 0.0012*). Further analysis of the regression model for GTR suggested an optimal cut point value for SSAP of 23.7 mm, above which predictability for failing to achieve GTR carried a sensitivity of 89% and specificity of 41%. CONCLUSIONS: This study is unique in its examination of endoscopic transsphenoidal surgical outcomes for pituitary adenomas with suprasellar extension. Our findings suggest that previously established grading systems based on lateral extension into the cavernous sinus lose their predictive value in lesions with suprasellar extension and, more specifically, with increasing suprasellar anterior-posterior diameter.

The role of surgical management for prolactin-secreting tumors in the era of dopaminergic agonists: An international multicenter report

ObjectiveFirst-line prolactin-secreting tumor (PST) management typically involves treatment with dopamine agonists and the role of surgery remains to be further explored. We examined the international experience of 12 neurosurgical centers to assess the patient characteristics, safety profile, and effectiveness of surgery for PST management. MethodsPatients surgically treated for PST from January 2017 through December 2020 were evaluated for surgical characteristics, outcomes, and safety. ResultsAmong 272 patients identified (65.1% female), the mean age was 38.0 ± 14.3 years. Overall, 54.4% of PST were macroadenomas. Minor complications were seen in 39.3% of patients and major complications were in 4.4%. The most common major complications were epistaxis and worsened vision. Most minor complications involved electrolyte/sodium dysregulation. At 3–6 months, local control on imaging was achieved in 94.8% of cases and residual/recurrent tumor was seen in 19.3%. Reoperations were required for 2.9% of cases. On multivariate analysis, previous surgery was significantly predictive of intraoperative complications (6.14 OR, p < 0.01) and major complications (14.12 OR, p < 0.01). Previous pharmacotherapy (0.27 OR, p = 0.02) and cavernous sinus invasion (0.19 OR, p = 0.03) were significantly protective against early endocrinological cure. Knosp classification was highly predictive of residual tumor or PST recurrence on 6-month follow-up imaging (4.60 OR, p < 0.01). There was noted institutional variation in clinical factors and outcomes. ConclusionOur results evaluate a modern, multicenter, global series of PST. These data can serve as a benchmark to compare with DA therapy and other surgical series. Further study and longer term outcomes could provide insight into how patients benefit from surgical treatment.

THU084 Corticotroph Tumor Type Influences Clinical Presentation In Patients With Nonfunctioning Pituitary Neuroendocrine Tumors

Abstract Disclosure: N. Al-Shamkhi: None. B. Edén Engström: None. O. Gudjonsson: None. J. Wikström: None. O. Casar-Borota: None. E. Rask: None. Introduction: According to the current World Health Organization classification of endocrine tumors the classification of non-functioning pituitary neuroendocrine tumors (NF-PitNET) is based on pituitary cell lineages, defined by immunohistochemical expression of anterior pituitary hormones and pituitary specific transcription factors. The second most common NF-PitNET type, after silent gonadotroph tumors, are silent corticotroph tumors that are regarded as a potentially more aggressive type. If there is indication for treatment, the first-line treatment is transsphenoidal surgery. Some, but not all studies have shown a higher degree of preoperative pituitary failure or more frequent postoperative pituitary failure in patients with silent corticotroph tumors compared to the other NF-PitNET. Objectives: We compared patients with silent corticotroph and silent gonadotroph tumors, and explored whether tumor type and radiological findings were associated with pre- or postoperative pituitary failure. Design and method: One hundred patients who underwent surgery for NF-PitNET at the same tertiary center were included. Data regarding age at surgery, sex, pre- and postoperative pituitary function and tumor type, were collected after chart review. Preoperative MRI examinations were revised regarding tumor volume and Knosp classification. Results: The majority, 72% (72/100) were classified as silent gonadotroph tumors followed by 18% (18/100) silent corticotroph tumors. Patients with silent corticotroph tumors were younger at surgery, P=0.003. There were no differences regarding sex, preoperative tumor volume, invasive growth on MRI, defined as Knosp grade &amp;gt; 3, pituitary failure or prolactin elevation between the two tumor types. Binary logistic regression showed that having a silent corticotroph tumor, P=0.04, odds ratio 5.7 (CI: 1.06-30.71), higher age at surgery, P=0.003, odds ratio 1.07 (CI: 1.02-1.13), and a larger preoperative tumor volume, P=0.01, odds ratio 1.18 (CI: 1.04-1.33), were all factors associated with an increased likelihood of having postoperative pituitary failure. Sex, invasive growth and preoperative prolactin elevation were not significant predictors of postoperative pituitary failure in the binary logistic regression. Conclusion: The results indicate that silent corticotroph tumors influence the clinical presentation of NF-PitNET. Patients with silent corticotroph tumors were significantly younger at surgery, and demonstrated an increased likelihood of postoperative pituitary failure. Presentation: Thursday, June 15, 2023

Anterior-posterior diameter is a key driver of resectability and complications for pituitary adenomas with suprasellar extension in endoscopic transsphenoidal surgery.

As endoscopic transsphenoidal approaches are more routinely selected for progressively larger pituitary adenomas with parasellar extension, understanding potential anatomical factors that limit resection and contribute to complications is becoming increasingly important for tailoring a surgical approach. This study aimed to reevaluate existing predictive tools for resectability in pituitary adenomas specifically with suprasellar extension, and furthermore identify any additional measurable features that may be more useful in preoperative planning. A single-center retrospective chart review of adult patients who underwent endoscopic transsphenoidal surgery for pituitary adenomas with suprasellar extension from 2015 to 2020 was performed. Preoperative MRIs were systematically assessed to assign a Knosp classification, a Zurich Pituitary Score (ZPS), and for dimensional measurements of the suprasellar aspect of the lesions. Univariate comparisons and multivariate regression models were employed to assess the influence of these factors on extent of resection and postoperative complications. Of the 96 patients with suprasellar pituitary adenomas who underwent endoscopic transsphenoidal surgery, 74 patients (77%) had a gross total resection (GTR). Neither Knosp grade nor ZPS score, even when dichotomized, demonstrated an association with GTR (Knosp 3A-4 versus Knosp 0-2, p = 0.069; ZPS III-IV versus ZPS I-II, p = 0.079). Multivariate regression analysis identified suprasellar anterior-posterior tumor diameter (SSAP) as the only significant predictor of extent of resection in this cohort (OR 0.951, 95% CI 0.905-1.000, p = 0.048*). A higher SSAP also had the strongest association with intraoperative CSF leaks (p = 0.0012*) and an increased overall rate of postoperative complications (p = 0.002*). Further analysis of the regression model for GTR suggested an optimal cut point value for SSAP of 23.7mm, above which predictability for failing to achieve GTR carried a sensitivity of 89% and a specificity of 41%. This study is unique in its examination of endoscopic transsphenoidal surgical outcomes for pituitary adenomas with suprasellar extension. Our findings suggest that previously established grading systems based on lateral extension into the cavernous sinus lose their predictive value in lesions with suprasellar extension and, more specifically, with increasing suprasellar anterior-posterior diameter.

A Novel Magnetic Resonance Imaging-Based Radiomics and Clinical Predictive Model for the Regrowth of Postoperative Residual Tumor in Non-Functioning Pituitary Neuroendocrine Tumor.

Background and Objectives: To develop a novel magnetic resonance imaging (MRI)-based radiomics-clinical risk stratification model to predict the regrowth of postoperative residual tumors in patients with non-functioning pituitary neuroendocrine tumors (NF-PitNETs). Materials and Methods: We retrospectively enrolled 114 patients diagnosed as NF-PitNET with postoperative residual tumors after the first operation, and the diameter of the tumors was greater than 10 mm. Univariate and multivariate analyses were conducted to identify independent clinical risk factors. We identified the optimal sequence to generate an appropriate radiomic score (Rscore) that combined pre- and postoperative radiomic features. Three models were established by logistic regression analysis that combined clinical risk factors and radiomic features (Model 1), single clinical risk factors (Model 2) and single radiomic features (Model 3). The models' predictive performances were evaluated using receiver operator characteristic (ROC) curve analysis and area under curve (AUC) values. A nomogram was developed and evaluated using decision curve analysis. Results: Knosp classification and preoperative tumor volume doubling time (TVDT) were high-risk factors (p < 0.05) with odds ratios (ORs) of 2.255 and 0.173. T1WI&T1CE had a higher AUC value (0.954) and generated an Rscore. Ultimately, the AUC of Model 1 {0.929 [95% Confidence interval (CI), 0.865-0.993]} was superior to Model 2 [0.811 (95% CI, 0.704-0.918)] and Model 3 [0.844 (95% CI, 0.748-0.941)] in the training set, which were 0.882 (95% CI, 0.735-1.000), 0.834 (95% CI, 0.676-0.992) and 0.763 (95% CI, 0.569-0.958) in the test set, respectively. Conclusions: We trained a novel radiomics-clinical predictive model for identifying patients with NF-PitNETs at increased risk of postoperative residual tumor regrowth. This model may help optimize individualized and stratified clinical treatment decisions.

Expression pattern of lncRNAs in pituitary adenomas

Non-functioning pituitary adenomas (NFPAs) are a group of pituitary tumors lacking manifestations linked to high hormone production, such as acromegaly and Cushing’s syndrome. NFPA carcinogenesis depends on several molecular players. Long non-coding RNAs (lncRNAs) are a class of molecular players whose role in tumorigenesis has just recently been recognized. In the current study, we appraised expressions of 5 lncRNAs, namely FGD5-AS1, ATP6V0E2-AS1, ARHGAP5-AS1, WWC2-AS2 and EPB41L4A-AS1 in NFPAs versus their corresponding non-tumoral samples. Expressions of ATP6V0E2-AS1, EPB41L4A-AS1, FGD5-AS1 and WWC2-AS2 were significantly increased in NFPA samples compared with adjacent non-tumoral samples (P values = 0.037, 0.007, 0.008 and 0.03, respectively). However, expression of ARHGAP5-AS1 was not different between NFPA samples and controls (P value = 0.62). EPB41L4A-AS1 and FGD5-AS1 could discriminate between NFPA samples and adjacent non-tumoral samples (P values = 0.03 and 0.04, respectively). However, the AUC values were not appropriate. There was a significant positive association between age of NFPA patients and invasiveness of NFPA (χ2 = 4.24, P value = 0.039). Moreover, there was a significant positive association between diseases duration and CSF leak (χ2 = 11.4, p value = 0.023). Finally, there was a significant positive association between tumor size and Knosp classification (χ2 = 11.5, p value = 0.02) and invasiveness of NFPA (χ2 = 6.12, p value = 0.04). The current study provides information about dysregulation of lncRNAs in NFPAs and warrants additional studies in this field.

Two- and three-dimensional endoscopic endonasal surgery of large and giant pituitary adenomas-outcome analysis of a series of 62 patients from a single pituitary center.

To analyze the perioperative course and clinical outcome of patients with large (lPA) and giant (gPA) pituitary adenoma who underwent endoscopic endonasal transsphenoidal surgery (EETS) using either two-dimensional (2D-E) or three-dimensional (3D-E) endoscopic systems. Single-center retrospective study of consecutive patients with lPA and gPA who underwent EETS between November 2008 and January 2023. LPA were defined as ≥ 3cm and < 4cm in diameter in at least one dimension and a volume of ≥ 10ccm; gPA were defined as larger than 4cm in diameter and with a greater volume than 10ccm. Patient data (age, sex, endocrinological and ophthalmological status) and tumor data (histology, tumor volume, size, shape, cavernous sinus invasion according to the Knosp classification) were analyzed. 62 patients underwent EETS. 43 patients were treated for lPA (69.4%) and 19 patients for gPA (30.6%). 46 patients (74.2%) underwent surgical resection using 3D-E and 16 patients 2D endoscopy (25.8%). Statistical results are referred to the comparison between 3D-E and 2D-E. Patients' age ranged from 23-88years (median 57), 16 patients were female (25.8%), 46 male (74.2%). Complete tumor resection was possible in 43.5% (27/62), partial resection in 56.5% (35/62). Resection rates did not differ between 3D-E (27 patients [43.5%]) and 2D-E (7 patients [43.8%], (p = 0.985). Visual acuity improved in 30 of 46 patients with preoperative deficit (65.2%). In the 3D-E group 21 of 32 patients (65.7%) improved, compared to 9 of 14 patients in the 2D-E group (64.3%). Improvement of visual field was achieved in 31 of 50 patients (62.0%; 22 of 37 patients in the 3D-E group [59.4%] and 9 of 13 patients in the 2D-E group [69.2%]). CSF leak was the most frequent complication and occurred in 9 patients (14.5%, [8 patients 17.4% 3D-E]) without statistical significance. Other surgical complications like postoperative bleeding, infection (meningitis) and deterioration of visual acuity and field were detected without statistical difference. New pituitary anterior lobe dysfunction was observed in 30 of 62 patients (48.4%, 8 patients [50.0%] in the 2D-E group and 22 patients [47.8%] in the 3D-E group). A transient deficit of posterior lobe was detected in 22.6% (14/62). No patient died within 30days of surgery. Although 3D-E may improve surgical dexterity, in this series of lPA and gPA it was not associated with higher resection rates compared to 2D-E. However, 3D-E visualization during resection of large and giant PA is safe and feasible and patient's clinical outcome is not different compared to 2D-E.

PD-L1 and tumor-infiltrating CD8+ lymphocytes are correlated with clinical characteristics in pediatric and adolescent pituitary adenomas.

To investigate the levels of tumor-infiltrating CD8+ lymphocytes (CD8+ TILs) and the expression of programmed cell death receptor ligand 1 (PD-L1) in the tumor microenvironment (TME) of pediatric and adolescent pituitary adenomas (PAPAs) and analyze the correlation between their levels and the clinical characteristics. A series of 43 PAPAs cases were enrolled over a period of 5 years. To compare the TME of PAPAs and adult PAs, 43 PAPAs cases were matched with 60 adult PAs cases (30 cases were between 20 and 40 years old, and 30 cases were older than 40 years) for main clinical characteristics. The expression of immune markers in PAPAs was detected by immunohistochemistry, and their correlation with the clinical outcomes was analyzed using statistical methods. In the PAPAs group, CD8+ TILs level was significantly lower (3.4 (5.7) vs. 6.1 (8.5), p = 0.001), and PD-L1 expression (0.040 (0.022) vs. 0.024 (0.024), p < 0.0001) was significantly higher as compared with the older group. The level of CD8+ TILs was negatively correlated with the expression of PD-L1 (r = -0.312, p = 0.042). Moreover, CD8+ TILs and PD-L1 levels were associated with Hardy (CD8, p = 0.014; PD-L1, p = 0.018) and Knosp (CD8, p = 0.02; PD-L1, p = 0.017) classification. CD8+ TILs level was associated with high-risk adenomas (p = 0.015), and it was associated with the recurrence of PAPAs (HR = 0.047, 95% CI 0.003-0.632, p = 0.021). Compared with the TME in adult PAs, the TME in PAPAs was found to express a significantly altered level of CD8+ TILs and PD-L1. In PAPAs, CD8+ TILs and PD-L1 levels were associated with clinical characteristics.

Endoscopic Transsphenoidal Surgery of Pituitary Adenomas: Preliminary Results of the Neurosurgery Service of Hospital Cristo Redentor

Abstract Objective The transsphenoidal surgery is a safe and effective technique to manage different skull base pathologies, such as pituitary adenomas. The purpose of the present study is to describe the initial experience with endoscopic transsphenoidal surgery in the treatment of pituitary adenoma patients at a tertiary hospital that is a reference in neurosurgery in Southern Brazil. Materials and Methods We retrospectively analyzed data from 60 patients with pituitary adenoma who underwent endoscopic transsphenoidal surgery between 2012 and 2019. Demographic characteristics, type of tumor, baseline hormonal changes, and clinical presentation were reported, as well as postoperative outcomes, tumor resection rate, and complications. Results The male/female ratio was of 0.53:1, and the mean age of the sample was of 54 (range: 26 to 79) years. In total, 34 patients (57%) presented the non-functioning adenoma subtype, and 26 (43%), the functioning adenoma subtype. In the non-functioning and functioning subtype groups, the average tumor diameter was of 32 mm and 18 mm, and the mean follow-up was of 27 months and 32 months respectively. Regarding visual symptoms, 79% of the patients showed improvement after surgery. Hormonal remission was achieved in 71% of the patients with prolactinoma, 85% of those with cushing, and 57% of patients with acromegaly. Overall, gross total resection (GTR) was achieved in 50% of patients but with a significantly lower rate among patients with tumors with parasellar growth (high grade on the Knosp classification). The most prevalent surgical complications observed were postoperative cerebrospinal fluid (CSF) leak and meningitis in 11% and 6% of the cases respectively. Conclusion We have shown that transsphenoidal endoscopic surgery can produce good results in the management of pituitary adenomas, with acceptable peri- and postoperative morbidity and mortality. Regardless of the technique used, the presence of large and giant pituitary adenomas with a high Knosp grade represents an enormous challenge for contemporary neurosurgery.

Pre- and post-clinical–radiological and surgical evaluation of patients with pituitary adenoma and metabolic syndrome

Background Pituitary adenomas are benign tumors located in the anterior hypophysis. Its appearance is associated with the development of parameters related to metabolic syndrome; therefore, surgical treatment could reduce associated morbimortality. Methods Pre- and post-surgical MRI, using the Hardy–Wilson and Knosp classification, and clinical data according to the American Association of Clinical Endocrinology (AACE) criteria for metabolic syndrome: all the patients were followed-up until 208.57 days were reviewed on 217 consecutive patients with pituitary surgery. Results Seventy-four patients were included in this study. There was a significant reduction in tumor size in mm3 [average pre- and post-surgery respectively: 12,362 mm3 (±12,397); 3,910 mm3 (±7,160)], (p < 0.0001). This was confirmed by the Hardy–Wilson and Knosp classification, where most patients went from grade IV C (33.7%) to grade 0 (12.1%), IA (20.2%), IIB (21.36%), and IIC (16.2%); as well as from grade 4 (24.3%) to grade 0 (45.9%), respectively. After surgery, there were statistically significant reductions in total serum levels of glucose [average pre- and post-surgery, respectively: 116 mg/dL (±26.9); 90 mg/dL (±10.2)], (p < 0.001), triglycerides [average pre- and post-surgery, 240 mg/dL (±102); 171 mg/dL (±60.5)], (p = 0.001); and HDL-c [average pre- and post-surgery, respectively: 39 mg/dL (±11.8); 44.6 mg/dL (±8.4)], (p = 0.029). The other parameters remained unchanged. Conclusion This is the first study to demonstrate the relationship between the presence of pituitary adenoma and significative changes in serum glucose, triglycerides and c-HDL related to metabolic syndrome.

Intraoperative characteristics of somatotropinomas

Background. Acromegaly is a rare disease associated with insulin‑like growth factor 1 hyperproduction due to the presence of pituitary adenoma in the patient. The first‑line treatment of such patients is surgical removal of the formation in order to normalize hormonal status. The main predictors of the ineffectiveness of surgical treatment and relapse of the disease are large tumor size, tumor invasion into the cavernous sinus, and high preoperative levels of growth hormone, as well as Ki‑6 % expression. The search for additional risk factors for disease recurrence, which according to various sources is approximately 30 % after primary surgical treatment, is an urgent task for researchers. In our work, we studied the intraoperative characteristics of the tumor, size of pituitary adenomas according to preoperative magnetic resonance imaging of the brain, degree of invasion of the tumor into the cavernous sinus according to the Knosp classification and compared them with disease outcomes after a year of follow‑up after surgical treatment.Aim. To identify new markers of aggressive progression of pituitary tumors.Materials and methods. A retrospective analysis of medical documentation, protocols of operations of 90 patients aged between 19 and 73 years with the diagnosis of growth hormone‑secreting pituitary adenoma was performed. The dia gnosis was confirmed based on clinical picture, laboratory and instrumental examination methods. All patients underwent endoscopic transsphenoidal removal of pituitary adenoma by one surgeon in one medical institution between 2017 and 2019.Results. Intraoperative characteristics of the tumor, such as the color of the solid component, density, degree of vascularization were compared with the results of laboratory and instrumental data, as well as the results of surgical treatment after a year of follow‑up.Conclusion. Such intraoperative characteristics of growth hormone‑secreting pituitary adenomas as the purplish‑gray color of the solid component, high vascularization, as well as dense‑elastic consistency of the tumor, can be considered high risk factors for continued tumor growth in the first 6 months after surgical treatment or relapse of the disease during a year of follow‑up.

The learning curve of endoscopic endonasal transsphenoidal surgery for pituitary adenomas with different surgical complexity.

To investigate the learning curve under different surgical complexity in endoscopic transsphenoidal approach for pituitary adenoma. 273 patients undergoing endoscopic transsphenoidal surgery for pituitary adenoma were collected retrospectively and divided into three groups chronologically (early, middle, and late periods). Surgical complexity was differentiated based on Knosp classification (Knsop grade 0-2 vs. Knosp grade 3-4), tumor maximum diameter (MD) (macroadenomas vs. giant adenomas), and history of previous surgery for pituitary adenoma (first operation vs. reoperation). Then the temporal trends in operative time, surgical outcomes, and postoperative complications were evaluated from early to late. The median operative time decrease from 169 to 147 min across the three periods (P = 0.001). A significant decrease in operative time was seen in the simple groups [Knosp grade 0-2 adenoma (169 to 137 min, P < 0.001), macroadenoma (166 to 140 min, P < 0.001), and first operation (170.5 to 134 min, P < 0.001)] but not in their complex counterparts (P > 0.05). The GTR rate increased from 51.6% to 69.2% (P = 0.04). The surgical period was an independent factor for GTR in the simple groups [Knosp grade 0-2 adenoma: OR 2.076 (95%CI 1.118-3.858, P = 0.021); macroadenoma: OR = 2.090 (95%CI 1.287-3.393, P = 0.003); first operation: OR = 1.809 (95%CI 1.104-2.966, P = 0.019)] but not in the complex groups. The biochemical cure rate increased over periods without statistical significance (from 37.5% to 56.3%, P = 0.181). Although intraoperative CSF leakage rose (from 20.9% to 35.2%) and postoperative CSF leakage reduced (from 12.1% to 5.5%), there was no statistically significant trend across the three time periods (P > 0.05). This study showed that complex operations might have a prolonged learning curve. Differentiating surgical difficulty and using multivariate combined analysis may be more helpful in clinical practice.

Pure Endoscopic Endonasal Treatment of Acromegaly; Classification, Remission Rates, Factors Affecting Remission, and Complications

Aim This study aims to evaluate the effectiveness of the pure endoscopic endonasal transsphenoidal (PEET) approach in treating acromegaly, focusing on remission criteria set by the 2002 and 2010 consensus guidelines. It also seeks to identify variables that affect remission and to analyze early postoperative IGF-1 levels 24 hours after surgery to determine their predictive value for remission. Material and Methods The study retrospectively reviewed the medical records of 129 acromegaly patients who underwent the PEET (Pure Endoscopic Endonasal Transsphenoidal) surgical approach between November 2010 and March 2016 at Ankara Numune Training and Research Hospital. Out of these, 124 patients with complete follow-up and laboratory data were included in the analysis. The study evaluated a range of variables including patients' symptoms, pre- and postoperative GH and IGF-1 levels, imaging results, and remission statuses based on the 2002 and 2010 consensus guidelines. Inclusion criteria for the study required patients to have specific preoperative and postoperative data and a minimum follow-up duration of at least 6 months. Results The study found statistically significant differences between the remission rates based on the 2002 and 2010 consensus criteria for acromegaly, with a 73.4% remission rate under the 2002 criteria and a 65.3% remission rate under the 2010 criteria (p=0.002). Multivariate logistic regression analysis indicated that the atypical nature of the adenoma (p=0.018) and surgical intervention due to recurrence (p=0.028) were significant negative factors affecting cure rates. The study also identified that advanced stages in Hardy Wilson (p=0.008) and Knosp (p&lt;0.001) classifications had a statistically significant negative impact on achieving a cure. No statistically significant predictive value was found for early postoperative IGF-1 levels in relation to cure (p=0.612). Conclusion: PEET is currently the preferred treatment option for GH-secreting pituitary adenomas and has high remission rates.

ODP368 Hyper-phosphorylation of β-catenin at Serine552: predictive marker of invasion and recurrence of Non-Functioning Pituitary Tumours (NFPTs)

Abstract Background NFPTs are the most common operated pituitary tumours and can present with visual field defects, hormone deficiencies and headache. Surgery is treatment of choice but recurrence rate is high ranging from 10-50%, depending on the extent of tumour removal. No confirmed predictive biomarkers for NFPT recurrence have been identified, apart from Ki-67. We applied high-throughput mass spectrometry-based phosphoproteomic approach to explore the phosphorylation pattern of proteins in NFPTs in order to identify predictive markers of invasion and recurrence. Methods Based on radiological, histopathological, and surgical features, NFPTs were sub-grouped into three groups: non-invasive (n=5), invasive (n=10) and recurrent (n=5) subtypes. Invasiveness was determined by radiology (Knosp classification 3&amp;4), histopathological invasion (bone, dura and mucosa) and intraoperative findings. Tumour recurrence was based on radiological data for a mean±SD follow-up of112±39 months. Fresh-frozen pituitary tumour tissues were used for protein extraction and phosphopeptides were enriched using TiO 2 and labelled with tandem mass tags and subjected tomass spectrometry (Orbitrap)for quantification. Candidate hyper-phosphorylated proteins were validated by immunohistochemistry in 200 additional tumour samples by immunoblotting (n=36). Results In total, we identified 3185 phosphopeptides and observed significant difference in phosphorylation levels of invasive and recurrent groups. Compared to non-invasive cases, in invasive group we found, 452 hyper and 93 hypo phosphorylated proteins, while in the recurrent group there were 790 hyper and 307 hypo phosphorylated proteins. Phospho-serine showed the highest level of difference (90.3%) among the groups, followed by threonine (8.9%) and tyrosine (0.8%). One of the top differentially phosphorylated proteins was Ser552 of β-catenin showing significant hyper-phosphorylation in recurrent (p&amp;lt;0. 001) and invasive (p&amp;lt;0. 001) NFPTs. We also observed hyper-phosphorylation in tumours with suprasellar (p&amp;lt;0. 05) and cavernous sinus extension (p&amp;lt;0. 01). There was no correlation with tumour diameter and volume. Receiver operating characteristics curve analysis was performed to find the optimal cut-off value of β-catenin pSer552 immunohistochemical H-score in patients who had recurrence (n=44) or non-recurrence (n=156)and observed an area under curve of 0.717 (95% CI: 0.61-0.80),indicating a good prognostic ability for theβ-catenin pSer552H-score. A cut-off value of 160 for theβ-catenin pSer552H-score gives a sensitivity of 69% and a specificity of 73% for tumour recurrence. Kaplan-Meier survival curve analysis shows strong statistical correlation in the recurrence free survival (p&amp;lt;0. 0001) and the nuclear positive staining of β-catenin pSer552 with a hazard ratio of 3.1 (95% CI 1.5-6.3). Conclusions our study has identified hyper-phosphorylation of β-catenin at the Ser552 in recurrent and invasive NFPT subgroups. The H-score of β-catenin p552 correlates with tumour recurrence free survival in a large cohort of NFPT patients, which supports that β-catenin pSer552 could be used as predictive biomarker for NFPT recurrence. Presentation: No date and time listed

ODP364 Prolactinomas in men: management challenges

Abstract Introduction Prolactinomas are the most common pituitary adenomas (Pas), with an estimated higher prevalence in women. Over 90% of prolactinomas are small, intrasellar tumors that rarely increase in size, but occasionally, these PAs can be aggressive or locally invasive and cause compression of vital structures. Usually, prolactinomas in male patients are large, invasive, but the reasons for the more aggressive course remain poorly understood. Also, male prolactinomas have a lower expression of estrogen receptor alpha (ERα), which is associated with higher proliferation rates, resistance to dopamine agonists and a poor prognosis (1). Objective To investigate the impact of sex-related differences in prolactinomas. Material and Methods We analyzed 76 patients with confirmed diagnosis of prolactinomas. The patient`s information was collected retrospectively between 2018 and 2021. The patients had a mean age of 40,9 years old (range 18-77) and the majority were males (56,75%). We identified 15 patients (11 males, 4 females) with prolactin (PRL) secreting macroadenomas who underwent pituitary surgery (transsphenoidal, ten patients; transcranial five patients, and three of them had two transsphenoidal interventions and one of them had two transcranial interventions), four had also radiotherapy (three patients had high voltage radiation therapy and one had gamma knife radiosurgery). In the group of patients who underwent pituitary surgery, mean pre-operative maximal diameter was 35.65 ± 14.83 mm (6 giant prolactinomas, all of them in males) with mean PRL levels at presentation of 3640 ng/ml (range 560–16000), with significant higher levels observed in male patients. Eleven patients had visual field defects and the same number had panhypopituitarism with hormonal replacement therapy. Only two patients (females) are now normoprolactinemic without treatment with dopamine agonists. Nine tumors were considered invasive, according to Knosp classification (grade 3-4). Two female patients had remission of the disease following surgery. Nine patients had residual tumors after surgery, with controlled PRL secretion under treatment with dopamine agonists. The nuclear positive cells for Ki-67 were quantified by bright field microscopy (magnification x200) using QuantCenter software, its values ranging from 1% to 20%, with a value of 15-20% in the case of a male patient with giant prolactinoma with cavernous sinus invasion. Conclusion Significantly higher prolactin concentrations are observed in men as compared to women, in PRL secreting pituitary adenomas. The reasons for a more aggressive course of prolactinomas in men remain poorly understood, the higher rates of proliferation markers, such as the Ki-67 labeling index or the mitotic count, the low expression of ERα may explain the more aggressive behavior in men. Reference: Maiter D. Prolactinomas in Men. In: Tritos N., Klibanski A. (eds) Prolactin Disorders. Contemporary Endocrinology. Humana, Cham, 2019. Pp 184-204. https://doi.org/10.1007/978-3-030-11836-5_1 Presentation: No date and time listed

Clinical application of the "sellar barrier's concept" for predicting intraoperative CSF leak in endoscopic endonasal surgery for pituitary adenomas with a machine learning analysis.

BackgroundRecently, it was defined that the sellar barrier entity could be identified as a predictor of cerebrospinal fluid (CSF) intraoperative leakage. The aim of this study is to validate the application of the sellar barrier concept for predicting intraoperative CSF leak in endoscopic endonasal surgery for pituitary adenomas with a machine learning approach.MethodsWe conducted a prospective cohort study, from June 2019 to September 2020: data from 155 patients with pituitary subdiaphragmatic adenoma operated through endoscopic approach at the Division of Neurosurgery, Università degli Studi di Napoli “Federico II,” were included. Preoperative magnetic resonance images (MRI) and intraoperative findings were analyzed. After processing patient data, the experiment was conducted as a novelty detection problem, splitting outliers (i.e., patients with intraoperative fistula, n = 11/155) and inliers into separate datasets, the latter further separated into training (n = 115/144) and inlier test (n = 29/144) datasets. The machine learning analysis was performed using different novelty detection algorithms [isolation forest, local outlier factor, one-class support vector machine (oSVM)], whose performance was assessed separately and as an ensemble on the inlier and outlier test sets.ResultsAccording to the type of sellar barrier, patients were classified into two groups, i.e., strong and weak barrier; a third category of mixed barrier was defined when a case was neither weak nor strong. Significant differences between the three datasets were found for Knosp classification score (p = 0.0015), MRI barrier: strong (p = 1.405 × 10−6), MRI barrier: weak (p = 4.487 × 10−8), intraoperative barrier: strong (p = 2.788 × 10−7), and intraoperative barrier: weak (p = 2.191 × 10−10). We recorded 11 cases of intraoperative leakage that occurred in the majority of patients presenting a weak sellar barrier (p = 4.487 × 10−8) at preoperative MRI. Accuracy, sensitivity, and specificity for outlier detection were 0.70, 0.64, and 0.72 for IF; 0.85, 0.45, and 1.00 for LOF; 0.83, 0.64, and 0.90 for oSVM; and 0.83, 0.55, and 0.93 for the ensemble, respectively.ConclusionsThere is a true correlation between the type of sellar barrier at MRI and its in vivo features as observed during endoscopic endonasal surgery. The novelty detection models highlighted differences between patients who developed an intraoperative CSF leak and those who did not.

Classifying Pituitary Adenoma Invasiveness Based on Radiological, Surgical and Histological Features: A Retrospective Assessment of 903 Cases.

Invasiveness is a major predictor of surgical outcome and long-term prognosis in patients with pituitary adenomas (PAs). We assessed PA invasiveness via radiological, surgical and histological perspectives to establish a classification scheme for predicting invasive behavior and poor prognosis. We retrospectively analyzed 903 patients who underwent transnasal-transsphenoidal surgery between January 2013 and December 2019. Radiological (hazard ratio (HR) 5.11, 95% confidence interval (CI): 3.98–6.57, p < 0.001) and surgical (HR 6.40, 95% CI: 5.09–8.06, p < 0.001) invasiveness better predicted gross-total resection (GTR) and recurrence/progression-free survival (RPFS) rates than did histological invasiveness (HR 1.44, 95% CI: 1.14–1.81, p = 0.003). Knosp grades 2 (HR 4.63, 95% CI: 2.13–10.06, p < 0.001) and 3 (HR 2.23, 95% CI: 1.39–3.59, p = 0.011) with surgical invasiveness were better predictors of prognosis than corresponding Knosp grades without surgical invasiveness. Classifications 1 and 2 were established based on radiological, surgical and histological invasiveness, and Knosp classification and surgical invasiveness, respectively. Classification 2 predicted RPFS better than Knosp classification and Classification 1. Overall, radiological and surgical invasiveness were clinically valuable as prognostic predictors. The convenience and good accuracy of Invasiveness in Classification 2 is useful for identifying invasive PAs and facilitating the development of treatment plans.