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W., Douali, Ismail Z., Rafi S., El Mghari G., and El Ansari N. "A rare case of an aggressive macroprolactinoma invading the sphenoid bone, clivus and cavernous sinuses posing the differential diagnosis with chordoma." World Journal of Advanced Research and Reviews 17, no. 3 (2023): 184–87. https://doi.org/10.5281/zenodo.8127743.
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Aggressive macroprolactinomas represent 0.4 to 4% of pituitary adenomas, they are more frequent in men, the positive diagnosis is easy, the evaluation of aggressiveness is essentially based on MRI and The treatment with dopaminergic agonist in first intention is now well established and should not be deferred apart from neurological emergency situations.
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Serra, Carlo, Jan-Karl Burkhardt, Giuseppe Esposito, et al. "Pituitary surgery and volumetric assessment of extent of resection: a paradigm shift in the use of intraoperative magnetic resonance imaging." Neurosurgical Focus 40, no. 3 (2016): E17. http://dx.doi.org/10.3171/2015.12.focus15564.
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OBJECTIVE The aim of this study was to quantitatively assess the role of intraoperative high-field 3-T MRI (3T-iMRI) in improving the gross-total resection (GTR) rate and the extent of resection (EOR) in endoscopic transsphenoidal surgery (TSS) for pituitary adenomas. METHODS Radiological and clinical data from a prospective database were retrospectively analyzed. Volumetric measurements of adenoma volumes pre-, intraoperatively, and 3 months postoperatively were performed in a consecutive series of patients who had undergone endoscopic TSS. The quantitative contribution of 3T-iMRI was measured as a percentage of the additional rate of GTR and of the EOR achieved after 3T-iMRI. RESULTS The cohort consisted of 50 patients (51 operations) harboring 33 nonfunctioning and 18 functioning pituitary adenomas. Mean adenoma diameter and volume were 21.1 mm (range 5–47 mm) and 5.23 cm3 (range 0.09–22.14 cm3), respectively. According to Knosp's classification, 10 cases were Grade 0; 8, Grade 1; 17, Grade 2; 12, Grade 3; and 4, Grade 4. Gross-total resection was the surgical goal (targeted [t]GTR) in 34 of 51 operations and was initially achieved in 16 (47%) of 34 at 3T-iMRI and in 30 (88%) of 34 cases after further resection. In this subgroup, the EOR increased from 91% at 3T-iMRI to 99% at the 3-month MRI (p < 0.05). In the 17 cases in which subtotal resection (STR) had been planned (tSTR), the EOR increased from 79% to 86% (p < 0.05) and GTR could be achieved in 1 case. Intrasellar remnants were present in 20 of 51 procedures at 3T-iMRI and in only 5 (10%) of 51 procedures after further resection (median volume 0.15 cm3). Overall, the use of 3T-iMRI led to further resection in 27 (53%) of 51 procedures and permitted GTR in 15 (56%) of these 27 procedures; thus, the GTR rate in the entire cohort increased from 31% (16 of 51) to 61% (31 of 51) and the EOR increased from 87% to 95% (p < 0.05). CONCLUSIONS The use of high-definition 3T-iMRI allowed precise visualization and quantification of adenoma remnant volume. It helped to increase GTR and EOR rates in both tGTR and tSTR patient groups. Moreover, it helped to achieve low rates of intrasellar remnants. These data support the use of 3T-iMRI to achieve maximal, safe adenoma resection.
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Lu, Liang, Xueyan Wan, Yu Xu, Juan Chen, Kai Shu, and Ting Lei. "Classifying Pituitary Adenoma Invasiveness Based on Radiological, Surgical and Histological Features: A Retrospective Assessment of 903 Cases." Journal of Clinical Medicine 11, no. 9 (2022): 2464. http://dx.doi.org/10.3390/jcm11092464.
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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.
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Tsiberkin, A. I., U. A. Tsoy, V. Yu Cherebillo, et al. "Early postoperative measurement of growth hormone level for prognosis of surgical outcomes in acromegaly." Terapevticheskii arkhiv 92, no. 10 (2020): 48–53. http://dx.doi.org/10.26442/00403660.2020.10.000490.
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Aim.To investigate the value of 24 hours post-surgery measurement of growth hormone (GH) level for prognosis of surgical outcomes in acromegaly.
 Materials and methods.A prospective cohort study included 45 patients with newly diagnosed acromegaly. The degree of parasellar extension was measured on the preoperative sellar magnetic resonance imaging according to the Knosps classification. All patients underwent a transsphenoid adenomectomy performed by one neurosurgeon. Basal GH level was measured at 24 hours after surgery. The efficacy of transsphenoidal adenomectomy evaluated at 12 months after surgery.
 Results.Acromegaly remission was achieved in 19 (42%) of 45 patients at 12 months after surgery. Pituitary microadenomas and the absence of paracellular invasion, corresponding to Knosp Grade 02, had low prognostic value for long-term remission due to low sensitivity (31.6%) and low specificity (38.5%), respectively. The highest prognostic value for acromegaly remission was showed for 24 hours post-surgery GH level with cut-off 1.30 ng/ml with sensitivity of 96.2% (95% confidence interval 81.199.8%) and specificity of 84.2% (95% confidence interval 62.494.4%).
 Conclusion.The study demonstrated the possibility of using GH level at 24 after surgery as a predictor for acromegaly remission. GH level 1.30 ng/ml at 24 hours after surgery showed better predictive value for long-term remission compared with the presence of microadenomas and Knosp Grade 02. The absence of decrease of GH level on the first day after surgery may serve as a reason for more close monitoring of patients in the postoperative period. Further studies in a larger number of observers are required to confirm our findings.
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Ferrés, Abel, Luís Reyes, Alberto Di Somma, et al. "The Prognostic-Based Approach in Growth Hormone-Secreting Pituitary Neuroendocrine Tumors (PitNET): Tertiary Reference Center, Single Senior Surgeon, and Long-Term Follow-Up." Cancers 15, no. 1 (2022): 267. http://dx.doi.org/10.3390/cancers15010267.
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Postoperative deserved outcomes in acromegalic patients are to normalize serum insulin-like growth factor (IGF-1), reduce the tumoral mass effect, improve systemic comorbidities, and reverse metabolic alterations. Pituitary neuroendocrine tumors (PitNET) are characterized to present a heterogeneous behavior, and growth hormone (GH)-secreting PitNET is not an exception. Promptly determining which patients are affected by more aggressive tumors is essential to guide the optimal postoperative decision-making process [prognostic-based approach]. From 2006 to 2019, 394 patients affected by PitNET were intervened via endoscopic endonasal transsphenoidal approach by the same senior surgeon. A total of 44 patients that met the criteria to be diagnosed as acromegalic and were followed up at least for 24 months (median of 66 months (26–156) were included in the present study. Multiple predictive variables [age, gender, preoperative GH and IGF-1 levels, maximal tumor diameter, Hardy’s and Knosp’s grade, MRI. T2-weighted tumor intensity, cytokeratin expression pattern, and clinicopathological classification] were evaluated through uni- and multivariate statistical analysis. Sparse probability of long-term remission was related to younger age, higher preoperative GH and- or IGF-1, group 2b of the clinicopathological classification, and sparsely granulated cytokeratin expression pattern. Augmented recurrence risk was related to elevated preoperative GH levels, tumor MRI T2-weighted hyperintensity, and sparsely granulated cytokeratin expression pattern. Finally, elevated risk for reintervention was related to group 2b of the clinicopathological classification, Knosp’s grade IV, and tumor MRI T2-weighted hyperintensity. In this study, the authors determined younger age, higher preoperative GH and- or IGF-1 levels, group 2b of the clinicopathological classification, Knosp’s grade IV, MRI T2-weighted tumor hyperintensity and sparsely granulated cytokeratin expression pattern are related to worse postoperative outcomes in long-term follow-up patients affected with GH-secreting PitNET.
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Staartjes, Victor E., Carlo Serra, Giovanni Muscas, et al. "Utility of deep neural networks in predicting gross-total resection after transsphenoidal surgery for pituitary adenoma: a pilot study." Neurosurgical Focus 45, no. 5 (2018): E12. http://dx.doi.org/10.3171/2018.8.focus18243.
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OBJECTIVEGross-total resection (GTR) is often the primary surgical goal in transsphenoidal surgery for pituitary adenoma. Existing classifications are effective at predicting GTR but are often hampered by limited discriminatory ability in moderate cases and by poor interrater agreement. Deep learning, a subset of machine learning, has recently established itself as highly effective in forecasting medical outcomes. In this pilot study, the authors aimed to evaluate the utility of using deep learning to predict GTR after transsphenoidal surgery for pituitary adenoma.METHODSData from a prospective registry were used. The authors trained a deep neural network to predict GTR from 16 preoperatively available radiological and procedural variables. Class imbalance adjustment, cross-validation, and random dropout were applied to prevent overfitting and ensure robustness of the predictive model. The authors subsequently compared the deep learning model to a conventional logistic regression model and to the Knosp classification as a gold standard.RESULTSOverall, 140 patients who underwent endoscopic transsphenoidal surgery were included. GTR was achieved in 95 patients (68%), with a mean extent of resection of 96.8% ± 10.6%. Intraoperative high-field MRI was used in 116 (83%) procedures. The deep learning model achieved excellent area under the curve (AUC; 0.96), accuracy (91%), sensitivity (94%), and specificity (89%). This represents an improvement in comparison with the Knosp classification (AUC: 0.87, accuracy: 81%, sensitivity: 92%, specificity: 70%) and a statistically significant improvement in comparison with logistic regression (AUC: 0.86, accuracy: 82%, sensitivity: 81%, specificity: 83%) (all p < 0.001).CONCLUSIONSIn this pilot study, the authors demonstrated the utility of applying deep learning to preoperatively predict the likelihood of GTR with excellent performance. Further training and validation in a prospective multicentric cohort will enable the development of an easy-to-use interface for use in clinical practice.
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Rouf, Siham, Soumiya Berrabeh, Lamiae Zarraa, and Hanane Latrech. "Knosp and revised Knosp classifications predict non-functioning pituitary adenoma outcomes: a single tertiary center experience." Journal of Medicine and Life 17, no. 11 (2024): 1007–11. https://doi.org/10.25122/jml-2024-0015.
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Momigliano, Nicoletta. "MM IA Pottery from Evans' Excavations at Knossos: A Reassessment." Annual of the British School at Athens 86 (November 1991): 149–271. http://dx.doi.org/10.1017/s0068245400014957.
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This article is a critical reassessment of the major Knossian deposits assigned by Evans to the Middle Minoan I A phase. It is divided into three main sections: first, an introduction, in which the author discusses the development of the definition of Knossian MM IA pottery; second, a detailed discussion of each deposit, based upon a systematic and first-hand re-examination of the ceramic material, and of the relevant written sources; third, a discussion of the problems concerning the classification of these deposits, and a typological study of their ceramic assemblages. The picture of Knossian MM IA pottery which emerges from this study is remarkably different from that presented by Evans, which is generally accepted. This has further implications not only for the study of Minoan pottery, but also for the early history of the site.
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Lang, Min, Danilo Silva, Lu Dai, et al. "Superiority of constructive interference in steady-state MRI sequencing over T1-weighted MRI sequencing for evaluating cavernous sinus invasion by pituitary macroadenomas." Journal of Neurosurgery 130, no. 2 (2019): 352–59. http://dx.doi.org/10.3171/2017.9.jns171699.
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OBJECTIVEPreoperatively determining the extent of parasellar invasion of pituitary macroadenomas is useful for surgical planning and patient counseling. Here, the authors compared constructive interference in steady state (CISS), a T2-weighted gradient-echo MRI sequence, to volume-interpolated breath-hold examination (VIBE), a T1-weighted gradient-echo MRI sequence, for evaluation of cavernous sinus invasion (CSI) by pituitary macroadenomas.METHODSVIBE and CISS images of 98 patients with pituitary macroadenoma were retrospectively analyzed and graded using the modified Knosp classification. The Knosp grades were correlated to surgical findings of CSI, which were determined intraoperatively using 0° and 30° endoscopes. The predictive accuracies for CSI according to the Knosp grades derived from the CISS and VIBE images were compared using receiver operating characteristic (ROC) curves. Postoperative MRI was used to evaluate the gross-total resection (GTR) rates.RESULTSThe CSI rate by pituitary macroadenomas was 27.6% (27 of 98 cases). Of 196 assessments (left and right sides of 98 macroadenomas), 45 (23.0%) had different Knosp grades when scored using VIBE versus CISS images. For the VIBE images, 0% of Knosp grade 0, 4.5% of grade 1, 23.8% of grade 2, 42.1% of grade 3A, 100% of grade 3B, and 83.3% of grade 4 macroadenomas were found to have CSI intraoperatively. For the CISS images, 0% of Knosp grade 0, 2.1% of grade 1, 31.3% of grade 2, 56.3% of grade 3A, 100% of grade 3B, and 100% of grade 4 macroadenomas were found to have CSI intraoperatively. Two pituitary macroadenomas were classified as grade 4 on VIBE sequences but grades 3A and 2 on CISS sequences; CSI was not observed intraoperatively in both cases. The GTR rate was 64.3% and 60.0% for high-grade (3A, 3B, and 4) macroadenomas classified using VIBE and CISS sequences, respectively. The areas under the ROC curves were 0.94 and 0.97 for VIBE- and CISS-derived Knosp grades (p = 0.007), respectively.CONCLUSIONSKnosp grades determined using CISS sequence images are better correlated with intraoperative CSI than those determined using VIBE sequence images. CISS sequences may be valuable for the preoperative assessment of pituitary macroadenomas.
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Akkus, Gamze, Fulya Odabaş, Sinan Sözütok, et al. "Novel Classification of Acromegaly in Accordance with Immunohistochemical Subtypes: Is There Really a Clinical Relevance?" Hormone and Metabolic Research 54, no. 01 (2021): 37–41. http://dx.doi.org/10.1055/a-1685-0655.
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AbstractAccording to the recent studies, immunohistochemical subtypes of growth hormone (GH) secreting adenomas have been considered as a predictive factor in determining the clinical outcomes including biochemical, radiologic, and endocrine remission. In a 20 year-of time period, acromegaly patients who were treated and followed at the Endocrinology Department of our University Hospital were screened for the study. Of total 98 patients, 65 patients who had been operated by transsphenoidal surgery and having postoperative specimens were included. Postoperative specimens of the surgery of the patients were classified into 3 groups based on the histochemical characteristics (densely, sparsely, and mixed). Parasellar extensions of pituitary tumors were classified into the five grades according to Knosp classification. The patients were investigated and evaluated for postoperative clinical progress, remission rates, comorbidities regarding with the histopathological patterns. Of total 65 patients, 31 were classified as densely granulated (group 1), 32 were classified as sparsely granulated (group 2), and 2 patients were assessed as mixed granulated (group 3). There was no difference between groups for age and gender. Pre-treatment of adenoma size in all groups was correlated with each other and the frequency of macroadenoma (1 vs. 2, 77.4 vs. 84.3%) was higher in two groups. Although mean initial GH levels in group 1 was higher than the other groups (p=0.03), IGF1 levels (age and gender matched) were similar in each group. Adenomas in all groups demonstrated noninvasive radiological characteristics (Knosp grade 0–1–2). Ki-67 proliferation index of both groups (64.5 vs. 50%) was predominantly 1%. With a similar follow-up period, the endocrine remission rates (GH<1 μg/l) in groups were 64 vs. 69%, respectively. In conclusion, classification according to immunohistochemical subtypes of growth hormone secreting adenomas may not be a qualified parameter to evaluate patients with patterns of aggressiveness, clinical outcomes, or treatment response.
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Buchy, Marie, Véronique Lapras, Muriel Rabilloud, et al. "Predicting early post-operative remission in pituitary adenomas: evaluation of the modified knosp classification." Pituitary 22, no. 5 (2019): 467–75. http://dx.doi.org/10.1007/s11102-019-00976-6.
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Park, Jung, Danielle Golub, Timothy G. White, et al. "504 Anterior-posterior Diameter Is a Key Driver of Resectability and Complications for Pituitary Adenomas With Suprasellar Extension in Endoscopic Transsphenoidal Surgery." Neurosurgery 70, Supplement_1 (2024): 154–55. http://dx.doi.org/10.1227/neu.0000000000002809_504.
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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.
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Акмырадов, С. Т., Ю. Г. Шанько, and В. А. Журавлев. "Somatotropin-Producing Pituitary Adenomas: Modern Methods of Diagnostics and Treatment. Literature Review." Неврология и нейрохирургия. Восточная Европа, no. 2 (May 19, 2021): 211–24. http://dx.doi.org/10.34883/pi.2021.11.2.036.
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В обзорной статье представлены эпидемиологические данные и характеристики соматотропинпродуцирующих аденом гипофиза. Подробно описаны классификация аденом гипофиза, клинические проявления соматотропинпродуцирующих аденом гипофиза в зависимости от размеров и распространенности опухоли за пределы турецкого седла. Представлены классификация прорастания опухоли в кавернозный синус (по Knosp) и эффект хирургического лечения в зависимости от степени распространения опухоли. Подробно рассмотрены методы комплексного лечения этих новообразований: хирургические – микрохирургическое и эндоскопическое эндоназальное транссфеноидальное удаление аденом гипофиза, медикаментозные – терапия аналогами соматостатина и антагонистами СТГ-рецепторов, и лучевые – стереотаксическая радиотерапия и радиохирургия. Подробно описаны основные факторы, влияющие на прогноз заболевания и достижение клинико-метаболической компенсации. В заключение определены основные направления исследований по проблеме соматотропин-продуцирующих аденом гипофиза. The review article presents epidemiological data and characteristics of somatotropin-producing pituitary adenomas. The classification of pituitary adenomas, clinical manifestations of somatotropin- producing pituitary adenomas, depending on the size and extent of the tumor beyond the sella turcica, are described in detail. The classification of tumor invasion into the cavernous sinus (according to Knosp) and the effect of surgical treatment depending on the degree of tumor spread are presented. The methods of complex treatment of these neoplasms are considered in detail: surgical – microsurgical method and endoscopic endonasal trans-sphenoidal removal of pituitary adenomas; medication – therapy with somatostatin analogs and antagonists of STHreceptors; radiation – stereotactic radiotherapy and radiosurgery. The main factors that influence the prognosis of the disease and achievement of clinical and metabolic compensation are described in detail. In conclusion, the main directions of research on the problem of somatotropin-producing pituitary adenomas are determined.
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Micko, Alexander, Johannes Oberndorfer, Wolfgang J. Weninger, et al. "Challenging Knosp high-grade pituitary adenomas." Journal of Neurosurgery 132, no. 6 (2020): 1739–46. http://dx.doi.org/10.3171/2019.3.jns19367.
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OBJECTIVEParasellar growth is one of the most important prognostic variables of pituitary adenoma surgery, with adenomas regarded as not completely resectable if they invade the cavernous sinus (CS) but potentially curable if they displace CS structures. This study was conducted to correlate surgical treatment options and outcomes to the different biological behaviors (invasion vs displacement) of adenomas with parasellar extension into the superior or inferior CS compartments or completely encasing the carotid artery (Knosp high grades 3A, 3B, and 4).METHODSThis was a retrospective cohort analysis of 106 consecutive patients with Knosp high-grade pituitary adenomas with parasellar extension who underwent surgery via a primary endoscopic transsphenoidal approach between 2003 and 2017. Biological tumor characteristics (surgical status of invasiveness and tumor texture, 2017 WHO classification, proliferation rate), extent of resection, and complication rate were correlated with parasellar extension grades 3A, 3B, and 4 on preoperative MRI studies.RESULTSInvasiveness was significantly less common in grade 3A (44%) than in grade 3B (72%, p = 0.037) and grade 4 (100%, p < 0.001) adenomas. Fibrous tumor texture was significantly more common in grade 4 (52%) compared to grade 3A (20%, p = 0.002), but not compared to grade 3B (28%) adenomas. Functioning macroadenomas had a significantly higher rate of invasiveness than nonfunctioning adenomas (91% vs 55%, p = 0.002). Mean proliferation rate assessed by MIB-1 was > 3% in all groups but without significant difference between the groups (grade 3A, 3.2%; 3B, 3.9%; 4, 3.7%). Rates of endocrine remission/gross-total resection were significantly higher in grade 3A (64%) than in grade 3B (33%, p = 0.021) and grade 4 (0%, p < 0.001) adenomas. In terms of complication rates, no significant difference was observed between grades.CONCLUSIONSAccording to the authors’ data, the biological behavior of pituitary adenomas varies significantly between parasellar extension patterns. Adenomas with extension into the superior CS compartment have a lower rate of invasive growth than adenomas extending into the inferior CS compartment or encasing the carotid artery. Consequently, a significantly higher rate of remission can be achieved in grade 3A than in grade 3B and grade 4 adenomas. Therefore, the distinction into grades 3A, 3B, and 4 is of importance for prediction of adenoma invasion and surgical treatment considerations.
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Glebauskiene, Brigita, Rasa Liutkeviciene, Alvita Vilkeviciute, et al. "Association of Ki-67 Labelling Index and IL-17A with Pituitary Adenoma." BioMed Research International 2018 (May 31, 2018): 1–7. http://dx.doi.org/10.1155/2018/7490585.
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The aim of the present study was to determine if the Ki-67 labelling index reflects invasiveness of pituitary adenoma and to evaluate IL-17A concentration in blood serum of pituitary adenoma patients. The study was conducted in the Hospital of Lithuanian University of Health Sciences. All pituitary adenomas were analysed based on magnetic resonance imaging findings. The suprasellar extension and sphenoid sinus invasion by pituitary adenoma were classified according to Hardy classification modified by Wilson. Knosp classification system was used to quantify the invasion of the cavernous sinus. The Ki-67 labelling index was obtained by immunohistochemical analysis with the monoclonal antibody, and serum levels of IL-17A were determined by enzyme-linked immunosorbent assay (ELISA). Sixty-nine PA tissue samples were investigated. Serum levels of IL–17A were determined in 60 patients with PA and 64 control subjects. Analysis revealed statistically significantly higher Ki-67 labelling index in invasive compared to noninvasive pituitary adenomas. Median serum IL-17A level was higher in the pituitary adenoma patients than in the control group. Conclusion. IL-17A might be a significant marker for patients with pituitary adenoma and Ki-67 labelling index in case of invasive pituitary adenomas.
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Voznyak, Oleksandr, Andrii Lytvynenko, Oleg Maydannyk, Roman Ilyuk, Yaroslav Zinkevych, and Nazarii Hryniv. "Outcomes of Transsphenoidal Surgery in Growth Hormone-Secreting Pituitary Adenomas." Indian Journal of Neurosurgery 10, no. 01 (2021): 061–64. http://dx.doi.org/10.1055/s-0041-1726134.
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AbstractGrowth hormone (GH)-secreting pituitary adenomas (PA) make up 15 to 20% of total amount of hormonally active adenomas. In addition to acromegaly and gigantism, these tumors cause deep metabolic disturbances. Its systemic impact leads to increased mortality ratio of 1.32 compared with general population. Surgical removal remains the priority treatment option in controlling acromegaly and provides endocrinologic remission in up to 72% patients. A total of 92 patients were included in the study. All surgeries were performed via microscopic transsphenoidal approach (TSA) by the senior author in our institution between December 2009 and October 2019. Only patients who were followed-up with 75 g oral glucose tolerance tests (OGTTs), GH, and insulin-like growth factor I (IFG-I) measurements preoperatively, 1 week, and every 6 months postoperatively were analyzed. Based on standard preoperative 1.5-T MR imaging with contrast enhancement, the adenomas were identified and distributed according to the size and KNOSP classification. The efficacy depends on KNOSP grade, which is directly correlated with invasiveness to cavernous sinus (CS). Grades 3 and 4 are unfavorable factors influencing prognosis. Excluding grade 0 adenomas, as the surgery was not difficult with the excellent outcomes, we reached 75% (36 out of 48) remission in grade 1 to 2 groups. In contrast, only 17% (2 out of 12) had successful outcomes after surgery alone. In conclusion, the study demonstrates the efficiency of TS surgery in patients with confirmed GH-secreting PA.
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Buchy, M., V. Lapras, M. Rabilloud, A. Vasiljevic, E. Jouanneau, and G. Raverot. "Facteurs prédictifs de rémission postopératoire précoce dans les tumeurs hypophysaires neuro-endocrines : évaluation de la classification KNOSP revisitée." Annales d'Endocrinologie 78, no. 4 (2017): 237. http://dx.doi.org/10.1016/j.ando.2017.07.069.
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Hlaváč, Michal, Andreas Knoll, Benjamin Mayer, et al. "Ten years’ experience with intraoperative MRI-assisted transsphenoidal pituitary surgery." Neurosurgical Focus 48, no. 6 (2020): E14. http://dx.doi.org/10.3171/2020.3.focus2072.
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OBJECTIVEMany innovations have been introduced into pituitary surgery in the quest to maximize the extent of tumor resection. Because of the deep and narrow surgical corridor as well as the heterogeneity of confronted pathologies, anatomical orientation and identification of the target tissue can become difficult. Intraoperative MRI (iMRI) may have the potential to increase extent of resection (EOR) in transsphenoidal pituitary surgery. Furthermore, it may simplify anatomical orientation and risk assessment in difficult cases. Here, the authors evaluated the additional value of iMRI for the resection of pituitary adenomas performed in the past 10 years in their department.METHODSThey performed a retrospective single-center analysis of patients treated for pituitary adenoma in their department after the introduction of iMRI between 2008 and 2018. Of 495 transsphenoidal approaches, 300 consecutive MRI-assisted surgeries for pituitary adenomas encompassing 294 patients were selected for further analysis. Microscopic, endoscopic, or endoscope-assisted microscopic transsphenoidal approaches were distinguished. EOR as well as additional resection following iMRI was evaluated via detailed volumetric analysis. Patients were stratified according to the Knosp adenoma classification. Furthermore, demographic data, clinical symptoms, endocrine outcome, and complications were evaluated. Univariable and multivariable Cox regression analyses of progression-free survival (PFS) were performed.RESULTSPituitary adenomas classified as Knosp grades 0–2 were found in 60.3% of cases (n = 181). The most common tumors were nonfunctioning adenomas (75%). Continued resection following iMRI significantly increased EOR (7.5%, p < 0.001) and the proportion of gross-total resections (GTRs) in transsphenoidal pituitary surgery (54% vs 68.3%, p < 0.001). Additional resection after iMRI was performed in 37% of cases. Only in the subgroup of patients with Knosp grades 0–2 adenomas treated with the microsurgical technique was additional resection significantly more common than in the endoscopic group (p = 0.039). Residual tumor volume, Knosp grade, and age were confirmed as independent predictors of PFS (p < 0.001, p = 0.021, and p = 0.029, respectively) in a multivariable Cox regression analysis. Improvement of visual field deficits was documented in 78.6% of patients whose optic apparatus had been affected preoperatively. Revision surgery was done in 7.3% of cases; in 5.6% of cases, it was performed for cerebrospinal fluid fistula.CONCLUSIONSIn this series, iMRI led to the detection of a resectable tumor remnant in a high proportion of patients, resulting in a greater EOR and higher proportion of GTRs after continued resection in microsurgical and endoscopic transsphenoidal resection of pituitary adenomas. The volume of residual tumor was the most important predictor of PFS. Given the study data, the authors postulated that every bit of removed tumor serves the patient and increases their chances of a favorable outcome.
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Mastorakos, Panagiotis, Davis G. Taylor, Ching-Jen Chen, Thomas Buell, Joseph H. Donahue, and John A. Jane. "Prediction of cavernous sinus invasion in patients with Cushing’s disease by magnetic resonance imaging." Journal of Neurosurgery 130, no. 5 (2019): 1593–98. http://dx.doi.org/10.3171/2018.2.jns172704.
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OBJECTIVECavernous sinus invasion (CSI) in Cushing’s disease (CD) negatively affects the probability of complete resection, biochemical cure, and need for adjuvant therapy. However, the prediction of CSI based on MRI findings has been inconsistent and variable. Among macroadenomas, the Knosp classification is the most widely utilized radiographic predictor of CSI, but its accuracy in predicting CSI and the probability of gross-total resection is limited in the setting of microadenomas or Knosp grade 0–2 macroadenomas. The authors noticed that the presence of a triangular shape of adenomas adjacent to the cavernous sinus on coronal MR images is frequently associated with CSI. The authors aimed to determine the correlation of this radiographic finding (“sail sign” [SS]) with CSI.METHODSThe authors performed a retrospective review of all patients with a pituitary lesion < 20 mm and a biochemical diagnosis of CD treated with endoscopic or microscopic transsphenoidal resection from November 2007 to May 2017. Overall 185 patients with CD were identified: 27 were excluded for negative preoperative imaging, 32 for lacking tumors adjacent to the sinus, 7 for Knosp grade 3 or higher, and 4 for inadequate intraoperative assessment of the CSI. Following application of inclusion and exclusion criteria, 115 cases were available for statistical analysis. Intraoperative CSI was prospectively evaluated at the time of surgery by one of two neurosurgical attending surgeons, and MRI data were evaluated retrospectively by a neurosurgical resident and attending neuroradiologist blinded to the intraoperative results.RESULTSA positive SS was identified in 23 patients (20%). Among patients with positive SS, 91% demonstrated CSI compared to 10% without an SS (p < 0.001). Using the SS as a predictor of CSI provided a sensitivity of 0.7 and a specificity of 0.98, with a positive predictive value (PPV) of 0.91 and a negative predictive value of 0.9. Among patients with positive SS, 30% did not achieve immediate postoperative remission, compared to 3.3% of patients without an SS (p < 0.001).CONCLUSIONSThe presence of a positive SS among Cushing’s adenomas adjacent to the CS provides strong PPV, specificity, and positive likelihood ratio for the prediction of CSI. This can be a useful tool for preoperative planning and for predicting the likelihood of long-term biochemical remission and the need for adjuvant radiosurgery.
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DU, DERYA, and OSMAN NACAR. "Pure Endoscopic Endonasal Treatment of Acromegaly; Classification, Remission Rates, Factors Affecting Remission, and Complications." Annals of Medical Research 30, no. 10 (2023): 1. http://dx.doi.org/10.5455/annalsmedres.2023.09.247.
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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<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.
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Rădoi, Mugurel, Florin Stefanescu, Ram Vakilnejad, and Lidia Gheorghitescu. "Combined surgical and medical treatment of giant prolactinoma: case report." Romanian Neurosurgery 30, no. 2 (2016): 200–208. http://dx.doi.org/10.1515/romneu-2016-0031.
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Abstract The operative management of giant pituitary prolactinoma represents a significant challenge for neurosurgeons, due to the degree of local tumor infiltration into adjacent structures such as cavernous sinus. The degree of parasellar tumor extension can be classified according to the Knosp grading system’ while suprasellar extension is qualified in accordance with the modified Hardys classification system. This report describes the case of a male patient with a giant pituitary prolactinoma in which a partial tumor resection via a subfrontal approach was achieved. Typically, resection rates of less than 50% have been reported following surgery on giant pituitary adenomas. Prolactin levels were very high, consistent with invasive giant prolactinoma. Our patient was treated with Cabergoline which eventually normalized the prolactin level and significantly reduced the size of the residual tumor. This case serves to illustrate that in the presence of significant suprasellar and parasellar extension, multi-modal treatment strategies with surgery and dopamine agonist, is the gold standard in the management of locally aggressive pituitary prolactinomas.
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Perondi, Gerson, Afonso Mariante, Fernando Azambuja, Gabriel Frizon Greggianin, Wanderson William dos Santos Dias, and Giulia Pinzetta. "Endoscopic Transsphenoidal Surgery of Pituitary Adenomas: Preliminary Results of the Neurosurgery Service of Hospital Cristo Redentor." Arquivos Brasileiros de Neurocirurgia: Brazilian Neurosurgery 42, no. 02 (2023): e89-e100. http://dx.doi.org/10.1055/s-0043-1769777.
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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.
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Kim, Y., S. Ahn, S. Jeun, Y. Lee, and J. Park. "P11.40.A Clinicopathological Analysis of High risk Pituitary Adenomas According to the 2017 WHO Classification System for Pituitary Neuroendocrine Tumors (PitNET)." Neuro-Oncology 24, Supplement_2 (2022): ii66. http://dx.doi.org/10.1093/neuonc/noac174.229.
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Abstract Background The 2017 WHO classification of pituitary tumors has revealed “high-risk pituitary neuroendocrine tumors (PitNETs)”, which were known to have high probability for recurrence. Tumor invasion was not included in the pathological grading and classification due to frequent lack of proper pathologic assessment. However, it mentioned tumor invasion as an important prognostic feature in identifying clinically aggressive adenomas. Material and Methods We performed a retrospective review of a prospectively collected dataset from January 2018 to March 2021. Patient’s clinical presentation, radiologic features, pathologic findings, and clinical outcome were gathered. Inter-group analysis was performed for high-risk versus low-risk tumors, and invasive versus non-invasive tumors. Results Among total 116 cases of PitNETs, high-risk and low-risk tumors were identified in 32 and 84 cases, respectively. The inter-group comparison showed no differences in clinical presentation, radiologic features, pathologic findings, and clinical outcomes.Invasive and non-invasive tumors were identified in 49 and 67 cases, respectively. The invasive group tumors were more symptomatic ( 29 (59.2%) vs. 30 (44.8%), p= 0.031), with larger tumor size over 40mm (9 (18.4%) vs. 1 (1.5%), p = 0.002), and more likely to have Knosp grade higher than 3. The gross-total resection was less achievable (7 (14.3%) vs 26 (38.8%), p = 0.007) However, Ki-67 index showed no significantly difference between the invasive group and non-invasive group (2.0 vs 2.0 , p= 0.556). Conclusion According to our study results, the pathologic diagnosis of a high-risk tumor does not necessarily seem to properly reflect the clinical aggressiveness. Tumor invasion, however, seems to better represent the aggressive tumors that requires proper and active treatment.
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García-Martínez, Araceli, Beatriz López-Muñoz, Carmen Fajardo, et al. "Increased E2F1 mRNA and miR-17-5p Expression Is Correlated to Invasiveness and Proliferation of Pituitary Neuroendocrine Tumours." Diagnostics 10, no. 4 (2020): 227. http://dx.doi.org/10.3390/diagnostics10040227.
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miR-17-5p and E2F1 have been described as deregulated in cancer, but they have scarcely been studied in pituitary neuroendocrine tumours (PitNETs). This study evaluates the relationship of E2F1 and miR-17-5p with the invasiveness and proliferation of PitNETs. In this cross-sectional descriptive study, we evaluated the expression of E2F1, MYC, and miR-17-5p by quantitative real time PCR analysis in 60 PitNETs: 29 gonadotroph (GT), 15 functioning somatotroph (ST), and 16 corticotroph (CT) tumours, of which 8 were silent (sCT). The clinical data were collected from the Spanish Molecular Register of Pituitary Adenomas (REMAH) database. We defined invasiveness according to the Knosp classification and proliferation according to a molecular expression of Ki-67 ≥ 2.59. E2F1 was more expressed in invasive than in non-invasive tumours in the whole series (p = 0.004) and in STs (p = 0.01). In addition, it was overexpressed in the silent subtypes (GTs and sCTs; all macroadenomas) and normoexpressed in the functioning ones (fCTs and STs; some microadenomas). miR-17-5p was more expressed in proliferative than in non-proliferative tumours (p = 0.041) in the whole series but not by subtypes. Conclusions: Our study suggests that in PitNETs, E2F1 could be a good biomarker of invasiveness, and miR-17-5p of proliferation, helping the clinical management of these tumours.
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Graffeo, Christopher S., Michael J. Link, Scott L. Stafford, Ian F. Parney, Robert L. Foote, and Bruce E. Pollock. "Risk of internal carotid artery stenosis or occlusion after single-fraction radiosurgery for benign parasellar tumors." Journal of Neurosurgery 133, no. 5 (2020): 1388–95. http://dx.doi.org/10.3171/2019.8.jns191285.
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OBJECTIVEStereotactic radiosurgery (SRS) is an accepted treatment option for patients with benign parasellar tumors. Here, the authors’ objective was to determine the risk of developing new or progressive internal carotid artery (ICA) stenosis or occlusion after single-fraction SRS for cavernous sinus meningioma (CSM) or growth hormone–secreting pituitary adenoma (GHPA).METHODSThe authors queried their prospectively maintained registry for patients treated with single-fraction SRS for CSM or GHPA in the period from 1990 to 2015. Study criteria included no prior irradiation and ≥ 12 months of post-SRS radiological follow-up. Pre-SRS grading of ICA involvement was applied according to the 1993 classification schemes of Hirsch for CSM or Knosp for GHPA.RESULTSThe authors conducted a retrospective review of 283 patients, 155 with CSMs and 128 with GHPAs. Ninety-three (60%) CSMs were Hirsch category 2 and 3 tumors; 97 (76%) GHPAs were Knosp grade 2–4 tumors. Median follow-up after SRS was 6.6 years (IQR 1–24.9 years). No GHPA or category 1 CSM developed ICA stenosis or occlusion. Three (5.2%) patients with category 2 CSMs had asymptomatic ICA stenosis (n = 2) or occlusion (n = 1); 1 (1.1%) category 2 CSM patient had transient ischemic symptoms. Five (14.3%) category 3 CSMs progressed to ICA occlusion (4 asymptomatic, 1 symptomatic). The median time to stenosis/occlusion was 4.8 years (IQR 1.8–7.6). Five- and 10-year risks of ICA stenosis/occlusion in category 2 and 3 CSM patients were 7.5% and 12.4%, respectively. Five- and 10-year risks of ischemic stroke from ICA stenosis/occlusion in category 2 and 3 CSM patients were both 1.2%. Multivariate analysis showed patient age (HR 0.92, 95% CI 0.86–0.98, p = 0.01), meningioma pathology (HR and 95% CI not defined, p = 0.03), and pre-SRS carotid category (HR 4.51, 95% CI 1.77–14.61, p = 0.004) to be associated with ICA stenosis/occlusion. Internal carotid artery stenosis/occlusion was not related to post-SRS tumor growth (HR and 95% CI not defined, p = 0.41).CONCLUSIONSNew or progressive ICA stenosis/occlusion was common after SRS for CSM but was not observed after SRS for GHPA, suggesting a tumor-specific mechanism unrelated to radiation dose. Pre-SRS ICA encasement or constriction increases the risk of ICA stenosis/occlusion; however, the risk of ischemic complications is very low.
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Chen, Juan, Xiang Guo, Zhuangzhuang Miao, et al. "Extra-Pseudocapsular Transsphenoidal Surgery for Microprolactinoma in Women." Journal of Clinical Medicine 11, no. 13 (2022): 3920. http://dx.doi.org/10.3390/jcm11133920.
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A recall for histological pseudocapsule (PS) and reappraisal of transsphenoidal surgery (TSS) as a viable alternative to dopamine agonists in the treatment algorithm of prolactinomas are getting vibrant. We hope to investigate the effectiveness and risks of extra-pseudocapsular transsphenoidal surgery (EPTSS) for young women with microprolactinoma, and to look into the factors that influenced remission and recurrence, and thus to figure out the possible indication shift for primary TSS. We proposed a new classification method of microprolactinoma based on the relationship between tumor and pituitary position, which can be divided into hypo-pituitary, para-pituitary and supra-pituitary groups. We retrospectively analyzed 133 patients of women (<50 yr) with microprolactinoma (≤10 mm) who underwent EPTSS in a tertiary center. PS were identified in 113 (84.96%) microadenomas intraoperatively. The long-term surgical cure rate was 88.2%, and the comprehensive remission rate was 95.8% in total. There was no severe or permanent complication, and the surgical morbidity rate was 4.5%. The recurrence rate with over 5 years of follow-up was 9.2%, and a lot lower for the tumors in the complete PS group (0) and hypo-pituitary group (2.1%). Use of the extra-pseudocapsule dissection in microprolactinoma resulted in a good chance of increasing the surgical remission without increasing the risk of CSF leakage or endocrine deficits. First-line EPTSS may offer a greater opportunity of long-term cure for young female patients with microprolactinoma of hypo-pituitary located and Knosp grade 0-II.
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Ferreli, F., M. Turri-Zanoni, F. R. Canevari, et al. "Endoscopic endonasal management of non-functioning pituitary adenomas with cavernous sinus invasion: a 10- year experience." Rhinology journal 53, no. 4 (2015): 308–16. http://dx.doi.org/10.4193/rhino14.309.
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Background: The management of Non-Functioning Pituitary Adenoma (NFPA) invading the cavernous sinus (CS) is currently a balancing act between the surgical decompression of neural structures, radiotherapy and a wait-and-see policy. Methods: We undertook a retrospective review of 56 cases of NFPA with CS invasion treated through an endoscopic endonasal approach (EEA) between 2000 and 2010. The Knosp classification was adopted to describe CS involvement using information from preoperative MRI and intraoperative findings. Extent of resection and surgical outcomes were evaluated on the basis of postoperative contrast-enhanced MRI. Endocrinological improvement and visual outcomes were assessed according to the most recent consensus criteria. Results: EEA was performed using direct para-septal, trans-ethmoidal-sphenoidal or trans-ethmoidal-pterygoidal-sphenoidal approach. Visual outcomes improved in 30 (81%) patients. Normalization or at least improvement of previous hypopituitarism was obtained in 55% of cases. A gross total resection was achieved in 30.3% of cases. The recurrence-free survival was 87.5%, with a mean follow-up of 61 months (range, 36-166 months). No major intraoperative or postoperative complications occurred. Discussion: EEA is a minimally-invasive, safe and effective procedure for the management of NFPA invading the CS. The extent of CS involvement was the main factor limiting the degree of tumor resection. The EEA was able to resolve the mass effect, preserving or restoring visual function, and obtaining adequate long-term tumor control.
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Zanier, Olivier, Matteo Zoli, Victor E. Staartjes, et al. "Machine learning-based clinical outcome prediction in surgery for acromegaly." Endocrine 75, no. 2 (2021): 508–15. http://dx.doi.org/10.1007/s12020-021-02890-z.
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Abstract Purpose Biochemical remission (BR), gross total resection (GTR), and intraoperative cerebrospinal fluid (CSF) leaks are important metrics in transsphenoidal surgery for acromegaly, and prediction of their likelihood using machine learning would be clinically advantageous. We aim to develop and externally validate clinical prediction models for outcomes after transsphenoidal surgery for acromegaly. Methods Using data from two registries, we develop and externally validate machine learning models for GTR, BR, and CSF leaks after endoscopic transsphenoidal surgery in acromegalic patients. For the model development a registry from Bologna, Italy was used. External validation was then performed using data from Zurich, Switzerland. Gender, age, prior surgery, as well as Hardy and Knosp classification were used as input features. Discrimination and calibration metrics were assessed. Results The derivation cohort consisted of 307 patients (43.3% male; mean [SD] age, 47.2 [12.7] years). GTR was achieved in 226 (73.6%) and BR in 245 (79.8%) patients. In the external validation cohort with 46 patients, 31 (75.6%) achieved GTR and 31 (77.5%) achieved BR. Area under the curve (AUC) at external validation was 0.75 (95% confidence interval: 0.59–0.88) for GTR, 0.63 (0.40–0.82) for BR, as well as 0.77 (0.62–0.91) for intraoperative CSF leaks. While prior surgery was the most important variable for prediction of GTR, age, and Hardy grading contributed most to the predictions of BR and CSF leaks, respectively. Conclusions Gross total resection, biochemical remission, and CSF leaks remain hard to predict, but machine learning offers potential in helping to tailor surgical therapy. We demonstrate the feasibility of developing and externally validating clinical prediction models for these outcomes after surgery for acromegaly and lay the groundwork for development of a multicenter model with more robust generalization.
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Shen, Chaodong, Xiaoyan Liu, Jinghao Jin, et al. "A Novel Magnetic Resonance Imaging-Based Radiomics and Clinical Predictive Model for the Regrowth of Postoperative Residual Tumor in Non-Functioning Pituitary Neuroendocrine Tumor." Medicina 59, no. 9 (2023): 1525. http://dx.doi.org/10.3390/medicina59091525.
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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.
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McKevitt, Chase, Ellie Gabriel, Lina Marenco Hillembrand, et al. "1235 Using Supervised Machine Learning to Validate a Novel Scoring System for the Prediction of Disease Remission of Functional Adenomas Following Transsphenoidal Resection." Neurosurgery 70, Supplement_1 (2024): 193. http://dx.doi.org/10.1227/neu.0000000000002809_1235.
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INTRODUCTION: Functional pituitary adenomas are common primary central nervous system tumors with potent systemic endocrinological effects. Postoperatively, remission rates range from 65-98%. METHODS: 392 adult patients who underwent primary resection of a functional pituitary adenoma at the three Mayo Clinic between 2006-2022 were retrospectively reviewed. Multivariate logistic regression was performed to identify variables predictive of disease remission. Variables found statistically significant on multivariate analysis were incorporated into our proposed pituitary-SCHEME score. Machine learning models were implemented to compare the accuracy of the pituitary-SCHEME score against the multivariate models. After training (314 patients) and cross-validation of the machine learning models, an independent testing set of 78 patients was performed. SPSS V27 and R4.2.1 were used for statistical analyses. RESULTS: 261 (66.6%) patients achieved post-operative biochemical remission. On multivariate analysis gross-total resection and Knosp-Grade 0,I,II adenomas were predictive of disease remission following resection, while macroadenomas (adenoma > 10mm), male sex, mammosomatotroph and Mixed Growth-Hormone + Prolactin adenomas were predictive of continued disease. In machine learning models, without Pituitary-SCHEME score, the K-Nearest Neighbors (KNN) model achieved the highest accuracy at 75.6% followed by Naive Bayes model. An increase in model sensitivity was achieved with inclusion of Pituitary-SCHEME score with the Linear-Discriminant-Analysis (LDA) model achieving the highest accuracy at 86.9%, followed by the Classification and Regression Trees (CART) model. The random forest model had the largest AUC-ROC among models with and without pituitary-SCHEME score. Model prediction accuracy (with vs. without pituitary-SCHEME score) were found to be statistically different based on Wilcoxon rank sum testing (p < 0.0001). CONCLUSIONS: The novel pituitary-SCHEME score, which incorporates perioperative and endocrinological measures, has promise as a clinical tool to predict patient outcomes following surgical resection of functional adenomas.
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Findlay, Matt, Mohammadmahdi Sabahi, Mohammed Azab, et al. "202 The Role of Surgical Management for Prolactinoma in the Era of Dopaminergic Agonists: An International Multicenter Report." Neurosurgery 70, Supplement_1 (2024): 52–53. http://dx.doi.org/10.1227/neu.0000000000002809_202.
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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.
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Wu, Zhe Bao, Chun Jiang Yu, Zhi Peng Su, Qi Chuan Zhuge, Jin Sen Wu, and Wei Ming Zheng. "Bromocriptine treatment of invasive giant prolactinomas involving the cavernous sinus: results of a long-term follow up." Journal of Neurosurgery 104, no. 1 (2006): 54–61. http://dx.doi.org/10.3171/jns.2006.104.1.54.
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Object The aim of this study was to observe long-term clinical outcomes in a group of patients treated with bromocriptine for invasive giant prolactinomas involving the cavernous sinus. Methods Data from 20 patients with invasive giant prolactinomas at the authors’ institutions between July 1997 and June 2004 were retrospectively reviewed. The criteria to qualify for study participation included: 1) tumor diameter greater than 4 cm, invading the cavernous sinus to an extent corresponding to Grade III or IV in the classification scheme of Knosp and colleagues; 2) serum prolactin (PRL) level greater than 200 ng/ml; and 3) clinical signs of hyperprolactinemia and mass effect. Among the 20 patients who met the criteria, six had undergone unsuccessful transcranial or transsphenoidal microsurgery prior to bromocriptine treatment and 14 patients received bromocriptine as the primary treatment. Eleven of the 20 patients underwent adjuvant radiotherapy. After a mean follow-up period of 37.3 months, the clinical symptoms in all patients improved by different degrees. Tumor volume on magnetic resonance images was decreased by a mean of 93.3%. In 11 patients, the tumor had almost completely disappeared; in the other nine patients, residual tumor invaded the cavernous sinus. Visual symptoms improved in 13 of the patients who had presented with visual loss. Eight patients had normal PRL levels. The postoperative PRL level was more than 200 ng/ml in seven patients. During the course of drug administration, cerebrospinal fluid leakage occurred in one patient, who subsequently underwent transsphenoidal surgery. No case of apoplexy occurred during bromocriptine treatment. Conclusions Dopamine agonist medications are effective as a first-line therapy for invasive giant prolactinomas, because they can significantly shrink tumor volume and control the PRL level. Tumor mass vanishes in some patients after bromocriptine treatment; in other patients with localized residual tumor, stereotactic radiosurgery is a viable option so that unnecessary surgery can be avoided. The application of radiotherapy does not reliably shrink tumor volume.
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Vieira Jr., Joaquim O., Arthur Cukiert, and Bernardo Liberman. "Magnetic resonance imaging of cavernous sinus invasion by pituitary adenoma diagnostic criteria and surgical findings." Arquivos de Neuro-Psiquiatria 62, no. 2b (2004): 437–43. http://dx.doi.org/10.1590/s0004-282x2004000300011.
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This study used MRI to define preoperative imaging criteria for cavernous sinus invasion (CSI) by pituitary adenoma (PA). MR images of 103 patients with PA submitted to surgery (48 with CSI) were retrospectively reviewed. The following MR signs were studied and compared to intraoperative findings (the latter were considered the gold standard for CSI detection): presence of normal pituitary gland between the adenoma and CS, status of the CS venous compartments, CS size, CS lateral wall bulging, displacement of the intracavernous internal carotid artery (ICA) by adenoma, grade of parasellar extension (Knosp-Steiner classification) and percentage of intracavernous ICA encased by the tumor. Statistical analysis was performed using qui-square testing and sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were obtained for each MR finding. The following signs have been found to represent accurate criteria for non-invasion of the CS: 1- normal pituitary gland interposed between the adenoma and the CS (PPV, 100%); 2- intact medial venous compartment (PPV, 100%); 3- percentage of encasement of the intracavernous ICA lower than 25% (NPV, 100%) and 4- medial intercarotid line not crossed by the tumor (NPV, 100%). Criteria for CSI were: 1- percentage of encasement of the intracavernous ICA higher than 45%; 2- occlusion of three or more CS venous compartments and 3- occlusion of the CS lateral venous compartment. The CS was very likely to be invaded if the inferior venous compartment was not detected (PPV. 92,8%), if the lateral intercarotid line was crossed (PPV. 96,1%) or if a bulging lateral dural wall of the CS was seen (PPV, 92,3%). The preoperative diagnosis of CSI by PA is extremely important since endocrinological remission is rarely obtained after microsurgery alone in patients with invasive tumors. The above mentioned MR imaging criteria may be useful in advising most of the patients preoperatively on the potential need for complimentary therapy after surgery.
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Pletnev, R. V., V. Yu Cherebillo, A. S. Shatilova, and S. A. Bayramova. "Intraoperative characteristics of somatotropinomas." Russian journal of neurosurgery 25, no. 1 (2023): 36–46. http://dx.doi.org/10.17650/1683-3295-2023-25-1-36-46.
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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.
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Dumitriu-Stan, Roxana-Ioana, Iulia-Florentina Burcea, Valeria Nicoleta Nastase, et al. "The Value of ER∝ in the Prognosis of GH- and PRL-Secreting PitNETs: Clinicopathological Correlations." International Journal of Molecular Sciences 24, no. 22 (2023): 16162. http://dx.doi.org/10.3390/ijms242216162.
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Pituitary neuroendocrine tumors (PitNETs) are divided into multiple histological subtypes, which determine their clinical and biological variable behavior. Despite their benign evolution, in some cases, prolactin (PRL) and growth hormone (GH)-secreting PitNETs may have aggressive behavior. In this study, we investigated the potential predictive role of ER∝, alongside the clinicopathological classification of PitNETs (tumor diameter, tumor type, and tumor grade). A retrospective study was conducted with 32 consecutive cases of PRL- and mixed GH- and PRL-secreting PitNETs (5 patients with prolactinomas and 27 with acromegaly, among them, 7 patients with GH- and PRL- co-secretion) who underwent transsphenoidal intervention. Tumor specimens were histologically and immunohistochemical examined: anterior pituitary hormones, ki-67 labeling index, CAM 5.2, and ER∝; ER∝ expression was correlated with basal PRL levels at diagnosis (rho = 0.60, p < 0.01) and postoperative PRL levels (rho = 0.58, p < 0.001). In our study, the ER∝ intensity score was lower in female patients. Postoperative maximal tumor diameter correlated with Knosp grade (p = 0.02); CAM 5.2 pattern (densely/sparsely granulated/mixed densely and sparsely granulated) was correlated with postoperative PRL level (p = 0.002), and with ki-67 (p < 0.001). The IGF1 level at diagnosis was correlated with the postoperative GH nadir value in the oral glucose tolerance test (OGTT) (rho = 0.52, p < 0.05). Also, basal PRL level at diagnosis was correlated with postoperative tumor diameter (p = 0.63, p < 0.001). At univariate logistic regression, GH nadir in OGTT test at diagnostic, IGF1, gender, and invasion were independent predictors of remission for mixed GH- and PRL-secreting Pit-NETs; ER∝ can be used as a prognostic marker and loss of ER∝ expression should be considered a sign of lower differentiation and a likely indicator of poor prognosis. A sex-related difference can be considered in the evolution and prognosis of these tumors, but further studies are needed to confirm this hypothesis.
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Baciu, Ionela, Iulia Florentina Burcea, Cristina Capatana, et al. "ODP364 Prolactinomas in men: management challenges." Journal of the Endocrine Society 6, Supplement_1 (2022): A515—A516. http://dx.doi.org/10.1210/jendso/bvac150.1072.
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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
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Rai, Ashutosh, Soujanya D. Yelamanchi, Bishan D. Radotra та ін. "ODP368 Hyper-phosphorylation of β-catenin at Serine552: predictive marker of invasion and recurrence of Non-Functioning Pituitary Tumours (NFPTs)". Journal of the Endocrine Society 6, Supplement_1 (2022): A517. http://dx.doi.org/10.1210/jendso/bvac150.1075.
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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&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&lt;0. 001) and invasive (p&lt;0. 001) NFPTs. We also observed hyper-phosphorylation in tumours with suprasellar (p&lt;0. 05) and cavernous sinus extension (p&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&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
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Matsueva, I. A., E. A. Vasukova, A. A. Paltsev, U. A. Tsoi, and E. N. Grineva. "Place of surgery in prolactinomas treatment (clinical study)." Russian Journal for Personalized Medicine 4, no. 5 (2024): 431–44. http://dx.doi.org/10.18705/2782-3806-2024-4-5-431-444.
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Relevance. Prolactinoma is one of the most common neuroendocrine tumors of the pituitary. Its prevalence 77,6 per 100,000 patients with pituitary masses. The first line of treatment for prolactinomas is drug therapy with dopamine agonists (DA). Cabergoline is the medicine of choice because it is more effective and has a better safety profile. In approximately 15 % of patients who fail to achieve remission of the disease even on the maximum tolerated dose of cabergoline, they are recommended to undergo transsphenoidal adenomectomy (TSA). However, in real clinical practice, when surgical treatment is performed despite achieving or nor achieving maximum tolerated dose of DA including being considered as first line of treatment. Knowing that risk of complications of TSA at the centers of excellence is practically zero and the development of remission is expected immediately after surgery, the choose of using TSA in the treatment of prolactinomas is being discussed.Purpose and objectives of the study. Using the example of a specialized neurosurgical hospital, study the population of patients operated prolactinomas, determine the reasons for performing TSA, compare the contribution of known factors influencing remission of the disease after surgical treatment, and identify among them the most significant for the study population.Materials and methods. The study included patients with prolactinoma who performed TSA at the V.A. Almazov National Medical Research Center in the period from 01.2018 to 03.2023, and the diagnosis of prolactinoma was confirmed by data from a morphological study of the surgical material (excatly, cells adenoma expressed prolactin). Based on the results of TSA, patients were divided into 2 groups depending on the outcome of the operation: a group of patients with succesful surgery and a group where there was no effect from the TSA (unsuccessful operation). The outcome of the operation was considered succesful when: 1) the fact of normoprolactinemia for 1 year after TSA, 2) to a significant (more than 50 %) reduction in the need for DA.Results. The study included 60 patients with prolactinoma who performed TSA. Among the included patients, there were 36 men (60 %) and 24 women (40 %). The median age at diagnosis was 43 (Q1–Q3: 38–47) years for men and, 52 (Q1–Q3: 41–60) years for women. In 26 (43 %) patients, the indications for surgery corresponded to clinical recommendations: meanwhile 34 patients (56 %) were operated on at the request of the patient/doctor’s choice. Patients didn’t differ in age in the two groups (p = 0.447). Patients in the unsuccessful surgery group received DA therapy for a longer period of time (48 against 9 months, p < 0.001) and their weekly dosage was higher compared to patients with a positive effect from surgery (4 vs. 2 mg/week, p < 0.001). There was a statistically significant difference in such indicators as visual field impairment, deficiency of hormones of the anterior pituitary gland before/after surgery (p > 0.05).Conclusion. In the study population, TSA was successful in 38 of them (63 %). The factors determining TSA success were the value of preoperative prolactin — 2476.5 ng/ml, the degree of invasion into the cavernous sinus according to the Knosp classification, the weekly dosage and duration of DA therapy.
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Shen, Xiaoxu, Qi Liu, Jian Xu, and Yang Wang. "Correlation between the Expression of Interleukin-6, STAT3, E-Cadherin and N-Cadherin Protein and Invasiveness in Nonfunctional Pituitary Adenomas." Journal of Neurological Surgery Part B: Skull Base, December 5, 2019. http://dx.doi.org/10.1055/s-0039-1700499.
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Abstract Objective This study aimed to investigate the expression of interleukin (IL)-6, signal transducer and activator of transcription 3 (STAT3), epithelial-cadherin (E- cadherin) and neural-cadherin (N-cadherin) proteins in nonfunctional pituitary adenomas, and their correlation with invasiveness. Method Thirty cases of nonfunctional pituitary adenoma pathological wax specimens were selected from our hospital, including 20 cases of invasive nonfunctional pituitary adenoma (INFPA) and 10 noninvasive nonfunctional pituitary adenomas (NNFPAs). Envision was used to detect IL-6, STAT3, E-cadherin , and N-cadherin in specimens. Statistical methods were used to analyze the correlation between the four proteins and the Knosp classification of nonfunctional pituitary adenomas. Result IL-6 and STAT3 were highly expressed in INFPAs but poorly expressed in NNFPAs. E-cadherin expression in INFPAs was lower than that in NNFPAs. N-cadherin was positive or strongly positive in both groups. Spearman's correlation analysis showed that the expression of IL-6 and STAT3 was positively correlated with Knosp's classification, whereas the expression of E-cadherin was negatively correlated with Knosp classification. Meanwhile, the expression of N-cadherin was not correlated with Knosp's classification. Conclusion The expression of the IL-6, STAT3, E-cadherin proteins were associated nonfunctional pituitary adenomas. However, the expression of N-cadherin was not correlated with nonfunctional pituitary adenomas.
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Araujo-Castro, Marta, Alberto Acitores Cancela, Carlos Vior, Eider Pascual-Corrales, and Víctor Rodríguez Berrocal. "Radiological Knosp, Revised-Knosp, and Hardy–Wilson Classifications for the Prediction of Surgical Outcomes in the Endoscopic Endonasal Surgery of Pituitary Adenomas: Study of 228 Cases." Frontiers in Oncology 11 (January 20, 2022). http://dx.doi.org/10.3389/fonc.2021.807040.
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PurposeTo evaluate which radiological classification, Knosp, revised-Knosp, or Hardy–Wilson classification, is better for the prediction of surgical outcomes in the endoscopic endonasal transsphenoidal (EET) surgery of pituitary adenomas (PAs).MethodsThis is a retrospective study of patients with PAs who underwent EET PA resection for the first time between January 2009 and December 2020. Radiological cavernous sinus invasiveness was defined as a Knosp or revised-Knosp grade &gt;2 or a grade E in the Hardy–Wilson classification.ResultsA total of 228 patients with PAs were included. Cavernous sinus invasion was evident in 35.1% and suprasellar extension was evident in 74.6%. Overall, surgical cure was achieved in 64.3% of patients. Surgical cure was lower in invasive PAs than in non-invasive PAs (28.8% vs. 83.1%, p &lt; 0.0001), and the risk of major complications was higher (13.8% vs. 3.4%, p = 0.003). The rate of surgical cure decreased as the grade of Knosp increased (p &lt; 0.001), whereas the risk of complications increased (p &lt; 0.001). Patients with Knosp 3B PAs tended to achieve surgical cure less commonly than Knosp 3A PAs (30.0% vs. 56.0%, p = 0.164). Similar results were observed based on the invasion and extension of Hardy–Wilson classification (stage A–C 83.1% vs. E 28.8% p &lt; 0.0001, grade 0–II 81.1% vs. III–IV 59.7% p = 0.008). The Knosp classification offered the greatest diagnostic accuracy for the prediction of surgical cure (AUC 0.820), whereas the invasion Hardy–Wilson classification lacked utility for this purpose (AUC 0.654).ConclusionThe Knosp classifications offer a good orientation for the estimation of surgical cure and the risk of complications in patients with PAs submitted to EET surgery. However, the invasion Hardy–Wilson scale lacks utility for this purpose.
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Yuhan, Li, Wu Zhiqun, Tian Jihui, and Pan Renlong. "Ki-67 labeling index and Knosp classification of pituitary adenomas." British Journal of Neurosurgery, April 27, 2021, 1–5. http://dx.doi.org/10.1080/02688697.2021.1884186.
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Chen, Yike, Feng Cai, Jing Cao, et al. "Analysis of Related Factors of Tumor Recurrence or Progression After Transnasal Sphenoidal Surgical Treatment of Large and Giant Pituitary Adenomas and Establish a Nomogram to Predict Tumor Prognosis." Frontiers in Endocrinology 12 (December 14, 2021). http://dx.doi.org/10.3389/fendo.2021.793337.
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BackgroundPituitary adenoma (PA) is a benign neuroendocrine tumor caused by adenohypophysial cells, and accounts for 10%-20% of all primary intracranial tumors. The surgical outcomes and prognosis of giant pituitary adenomas measuring ≥3 cm in diameter differ significantly due to the influence of multiple factors such as tumor morphology, invasion site, pathological characteristics and so on. The aim of this study was to explore the risk factors related to the recurrence or progression of giant and large PAs after transnasal sphenoidal surgery, and develop a predictive model for tumor prognosis.MethodsThe clinical and follow-up data of 172 patients with large or giant PA who underwent sphenoidal surgery at the Second Affiliated Hospital of Zhejiang University School of Medicine from January 2011 to December 2017 were retrospectively analyzed. The basic clinical information (age, gender, past medical history etc.), imaging features (tumor size, invasion characteristics, extent of resection etc.), and histopathological characteristics (pathological results, Ki-67, P53 etc.) were retrieved. SPSS 21.0 software was used for statistical analysis, and the R software was used to establish the predictive nomogram.ResultsSeventy out of the 172 examined cases (40.7%) had tumor recurrence or progression. The overall progress free survival (PFS) rates of the patients at 1, 3 and 5 years after surgery were 90.70%, 79.65% and 59.30% respectively. Log-rank test indicated that BMI (P &lt; 0.001), Knosp classification (P &lt; 0.001), extent of resection (P &lt; 0.001), Ki-67 (P &lt; 0.001), sphenoidal sinus invasion (P = 0.001), Hardy classification (P = 0.003) and smoking history (P = 0.018) were significantly associated with post-surgery recurrence or progression. Cox regression analysis further indicated that smoking history, BMI ≥25 kg/m2, Knosp classification grade 4, partial resection and ≥3% Ki-67 positive rate were independent risk factors of tumor recurrence or progression (P &lt; 0.05). In addition, the nomogram and ROC curve based on the above results indicated significant clinical value.ConclusionThe postoperative recurrence or progression of large and giant PAs is related to multiple factors and a prognostic nomogram based on BMI (≥25 kg/m2), Knosp classification (grade 4), extent of resection (partial resection) and Ki-67 (≥3%) can predict the recurrence or progression of large and giant PAs after transnasal sphenoidal surgery.
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Simander, Gabriel, Per Olof Eriksson, Peter Lindvall, and Lars-Owe D. Koskinen. "Intrasellar pressure in patients with pituitary adenoma – relation to tumour size and growth pattern." BMC Neurology 22, no. 1 (2022). http://dx.doi.org/10.1186/s12883-022-02601-9.
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Abstract Background Only a few earlier publications on intrasellar pressure (ISP) have not been able to fully clarify any association between ISP and pituitary adenoma size and growth pattern. The aim of the study was to determine if intrasellar pressure (ISP) is elevated in patients with pituitary adenoma, and if the pressure is associated with tumour size and growth pattern. Methods The study included 100 patients operated for suspected pituitary adenoma, who have had their ISP measured intraoperatively. All adenomas were classified on the basis of Knosp and SIPAP, from which further classification of invasiveness was performed. MRT examinations were used to calculate the tumour volume and diameter in three axes. Results After exclusions, 93 cases were analysed. The mean ISP was 23.0 ± 8.4 mmHg. There were positive correlations between ISP and tumour volume and tumour diameters along all three axes. Coronal tumour diameter showed the strongest correlation with ISP elevation in a multivariate effect test. Adenomas classified as parasellar invasive (Knosp grade 3–4) showed higher mean ISP than adenomas considered as non-invasive (Knosp 0–2). Conclusions ISP is affected by tumour anatomy and correlates positively with tumour volume. Tumour width, i.e. diameter in the coronal plane, appears to be the measure that most strongly affects the ISP. This is confirmed by the association between ISP elevation and parasellar growth.
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Huang, Jinxiang, Xinjie Hong, Zheng Cai, et al. "The learning curve of endoscopic endonasal transsphenoidal surgery for pituitary adenomas with different surgical complexity." Frontiers in Surgery 10 (March 21, 2023). http://dx.doi.org/10.3389/fsurg.2023.1117766.
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ObjectiveTo investigate the learning curve under different surgical complexity in endoscopic transsphenoidal approach for pituitary adenoma.Methods273 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.ResultsThe 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 &lt; 0.001), macroadenoma (166 to 140 min, P &lt; 0.001), and first operation (170.5 to 134 min, P &lt; 0.001)] but not in their complex counterparts (P &gt; 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 &gt; 0.05).ConclusionThis 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.
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Uraki, Shinsuke, Hiroyuki Ariyasu, Asako Doi, et al. "SAT-301 Relationship Between Clinicopathological Aspects and MSH6/MSH2 and PD-L1 Expressions in Clinically Nonfunctioning Pituitary Adenomas." Journal of the Endocrine Society 4, Supplement_1 (2020). http://dx.doi.org/10.1210/jendso/bvaa046.129.
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Abstract Introduction: Mismatch repair (MMR) genes are associated with the MMR mechanism that corrects DNA polymerase misincorporation errors. We analyzed the aggressive pituitary adenomas (PAs) associated with Lynch syndrome due to germline mutation in the MMR gene. Reduced expression of MMR genes mutS homologs 6/2 (MSH6/2) directly promotes PA growth (1, 2). MMR gene expression and programmed cell death 1 ligand 1 (PD-L1) expression are involved in tumor immunity with immune checkpoint inhibitors, but the direct association in PAs is not fully understood. Hypothesis and Objectives: MSH6/2 and PD-L1 expression could affect PA proliferation and invasion by pathological classification of nonfunctioning (NF) PAs because the proliferation and invasiveness differ depending on the PA histological subtype. In this study, we therefore analyzed the correlation between MSH6/2 and PD-L1 mRNA expression levels and clinicopathological factors related to tumor proliferation using human NFPAs. Experimental Design: We performed immunohistochemistry to classify the NFPAs into gonadotroph adenomas (GAs), silent corticotroph adenomas (SCAs), null cell adenomas (NCAs) and pituitary transcription factor 1 (PIT1) lineage PAs according to 2017 WHO classifications. Quantitative analyses were by real-time PCR to detect MSH6/2 and PD-L1 mRNA expressions in NFPAs (n = 89). We also performed statistical analyses of the expressions and clinicopathological factors such as Knosp Grade and histological subtypes. We investigated the effect of MSH6 knockout on cell proliferation and PD-L1 expression in AtT-20ins cells. Major Results: MSH6/2 expression was positively associated with PD-L1 expression. MSH6/2 and PD-L1 expressions are significantly lower in invasive NFPAs with Knosp Grade 3–4 or recurrence than in non-invasive NFPAs with Knosp Grade 1–2. Their expression is significantly lower in SCAs and NCAs than in GAs. Although MSH6/2 expression also tends to be lower, the PD-L1 expression tends to be higher in PIT1 lineage PAs, which is unlike SCAs and NCAs. MSH6 knockout in AtT-20ins significantly decreased PD-L1 expression with cell proliferation promotion. Interpretation of results and Conclusion: MSH6/2 and PD-L1 expressions of SCAs, NCAs, and PIT1 lineage PAs compared to GAs were thought to contribute to their clinically aggressive behaviors. The molecular mechanism of the difference in clinical features of NFPAs was partially elucidated. In particular, reduced expressions of MSH6/2 were thought to be useful for predicting the proliferation and invasiveness of NFPAs. References: (1) Uraki S et al., Endocr J. 2017;64(9):895–906 (2) Uraki S et al., J Clin Endocrinol Metab. 2018;103(3):1171–1179. Declarations of conflicts of Interest: No authors declare any conflicts of interest.
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Fang, Yi, He Wang, Ming Feng, et al. "Application of Convolutional Neural Network in the Diagnosis of Cavernous Sinus Invasion in Pituitary Adenoma." Frontiers in Oncology 12 (April 14, 2022). http://dx.doi.org/10.3389/fonc.2022.835047.
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ObjectivesConvolutional neural network (CNN) is a deep-learning method for image classification and recognition based on a multi-layer NN. In this study, CNN was used to accurately assess cavernous sinus invasion (CSI) in pituitary adenoma (PA).MethodsA total of 371 patients with PA were enrolled in the retrospective study. The cohort was divided into the invasive (n = 102) and non-invasive groups (n = 269) based on surgically confirmed CSI. Images were selected on the T1-enhanced imaging on MR scans. The cohort underwent a fivefold division of randomized datasets for cross-validation. Then, a tenfold augmented dataset (horizontal flip and rotation) of the training set was enrolled in the pre-trained Resnet50 model for transfer learning. The testing set was imported into the trained model for evaluation. Gradient-weighted class activation mapping (Grad-CAM) was used to obtain the occlusion map. The diagnostic values were compared with different dichotomizations of the Knosp grading system (grades 0-1/2-4, 0-2/3a-4, and 0-3a/3b-4).ResultsBased on Knosp grades, 20 cases of grade 0, 107 cases of grade 1, 82 cases of grade 2, 104 cases of grade 3a, 22 cases of grade 3b, and 36 cases of grade 4 were recorded. The CSI rates were 0%, 3.7%, 18.3%, 37.5%, 54.5%, and 88.9%. The predicted accuracies of the three dichotomies were 60%, 74%, and 81%. The area under the receiver operating characteristic (AUC-ROC) of Knosp grade for CSI prediction was 0.84; the cutoff was 2.5 with a Youden value of 0.62. The accuracies of the CNN model ranged from 0.80 to 0.96, with AUC-ROC values ranging from 0.89 to 0.98. The Grad-CAM saliency maps confirmed that the region of interest of the model was around the sellar region.ConclusionsWe constructed a CNN model with a high proficiency at CSI diagnosis. A more accurate CSI identification was achieved with the constructed CNN than the Knosp grading system.
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Kuptsov, Artem, Javier Abarca-Olivas, Irene Monjas-Cánovas, et al. "Anatomical-radiological aspects and their influence on the results of pituitary adenomas endoscopic endonasal surgery." Journal of Neurological Surgery Part B: Skull Base, May 17, 2023. http://dx.doi.org/10.1055/a-2095-6442.
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Introduction Endoscopic endonasal surgery has globally improved postoperative results in pituitary adenomas. Material and methods We retrospectively analyzed 101 patients who underwent endonasal endoscopic surgery for pituitary adenomas in the period 2016-2021. Epidemiological variables, preoperative radiological factors including tumor volume, tumor appearance, cavernous sinus invasion (modified Knosp scale), degree of extension according to the SIPAP classification, preoperative visualization of the healthy gland on magnetic resonance imaging (MRI) were collected as well as intra and postoperative cerebrospinal fluid (CSF) leak. As a variable of interest, the degree of tumoral resection and the preservation of hormonal function were collected. Results Among the preoperative factors related to greater tumoral resection we found a lesser tumoral extension according to the SIPAP scale and the absence of a postoperative CSF leak had a statistically significant relation with greater hormonal preservation. Conclusion The SIPAP classification is a simple-to-measure preoperative radiological variable that could predict the extent of resection and conversely, the occurrence of a postoperative CSF leak has been associated with an inferior endocrinological outcome in this type of surgery.
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Al-Shamkhi, Nasrin, Britt Edén Engström, Olafur Gudjonsson, Johan Wikström, Olivera Casar-Borota, and Eva Rask. "THU084 Corticotroph Tumor Type Influences Clinical Presentation In Patients With Nonfunctioning Pituitary Neuroendocrine Tumors." Journal of the Endocrine Society 7, Supplement_1 (2023). http://dx.doi.org/10.1210/jendso/bvad114.1164.
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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 &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
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Cunha, Clara, Cátia Ferrinho, Eugénia Silva, et al. "MON-310 Factors Associated with Remission After Surgery for Acromegaly." Journal of the Endocrine Society 4, Supplement_1 (2020). http://dx.doi.org/10.1210/jendso/bvaa046.932.
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Abstract Background: Acromegaly is a disorder characterized by excessive growth hormone (GH) secretion, which, in most cases, is caused by a GH secreting adenoma. Surgical removal of the tumor via a transsphenoidal approach is the first choice treatment for most patients. The remission rate after an initial resection is 80 to 90 percent for microadenomas and less than 50 percent for macroadenomas. Objective: To analyze predictive factors of remission in acromegaly patients who underwent transsphenoidal surgery for GH secreting adenoma. Methods: From January 2006 to October 2019, 75 patients with GH secreting pituitary adenoma were evaluated at our center. Patients who had undergone medical treatment or radiotherapy as first treatment were excluded. A total of 60 patients were included in the analysis. Remission was defined as normal serum insulin-like growth factor-1 (IGF-1) age and sex adjusted and a random serum GH less than 1 ng/mL and/or nadir GH during oral glucose tolerance test &lt;0.4 ng/mL. Results: We evaluated 60 patients (41 females and 19 males), with a mean age at diagnosis of 49.6 (ranged from 23 to 77 years). Mean initial IGF-1 was 905.3 ng/mL (range 100-324) and mean initial GH was 25.0 ng/mL (&lt;2.5). Macroadenomas were more common than microadenomas (48 vs 12). The average maximum tumor diameter was 15.6 mm and 21 patients were graded as Knosp 3 or 4, which indicated cavernous sinus invasion. Patients were follow for 11.8 years. Overall, the remission rate was 50.0% after surgery. Mean age of patients in surgical remission (51.6 years) was higher than those patients not in remission (47.5 years) (p=0.439). Remission rates for microadenomas and macroadenomas were 75.0% and 44.9%, respectively (p=0.04). Patients who achieved remission had smaller tumors compared with those who failed to attain remission (mean diameter 11.6mm versus 17.8 mm). Using the Knosp classification system and preoperative magnetic resonance images to determine cavernous sinus invasion, Knosp grade 3 to 4 tumors were found in 5 patients in remission and in 16 patients with persistence of disease (p=0.003). Patients who achieved remission had a significantly lower preoperative IGF-1 level (650.5 ng/mL) compared with those who did not (1211.0 ng/mL) (p=0.04). Preoperative GH levels were lower for the patients who achieved remission (18.7 ng/mL) than for those who did not (32.5 ng/mL, p=0.006). Conclusions: In our study, predictors of biochemical remission after surgery were smaller tumor size, lower Knosp grade, and lower preoperative GH and IGF-1 levels.
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Fayez, Feras, Ahmed Abougamil, Francesca Vitulli, et al. "Is Knosp enough? A novel classification for Acromegaly: a retrospective analysis of cure rates and outcome predictors in a large tertiary centre." Acta Neurochirurgica 167, no. 1 (2025). https://doi.org/10.1007/s00701-025-06477-9.
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