Context Growth hormone pituitary adenoma (GHPA), a major subtype of pituitary adenoma (PA), can lead to progressive somatic disfigurement, multiple complications, and even increased mortality. The efficacy of current treatments is limited; thus, a novel pharmacological treatment is urgently needed. As a histone acetyltransferase (HAT) coactivator, p300 can regulate the transcription of several genes that are crucial for PA tumorigenesis and progression. However, the role of p300 and its catalytic inhibitor in GHPA is still unclear. Objective We aimed to identify the expression of p300 in GHPA and in normal pituitary glands. Methods The expression of p300 was detected in GHPA and normal pituitary tissues. Genetic knockdown was performed by siRNA. The efficacy of the p300 inhibitor A-485 in the cell cycle, proliferation, apoptosis, and hormone secretion was investigated by flow cytometry, ELISAs, Western blotting, and qRT-PCR. RNA sequencing, bioinformatic analysis, and subsequent validation experiments were performed to reveal the potential biological mechanism of A-485. Results High expression of p300 was found in GHPA tissues compared with normal pituitary tissues. Knockdown of p300 inhibited cell proliferation and clone formation. Treatment with A-485 suppressed cell growth and inhibited the secretion of GH in vitro and in vivo. Further mechanistic studies showed that A-485 could downregulate the expression or activity of several oncogenes, such as genes in the Pttg1, c-Myc, cAMP and PI3K/AKT/mTOR signaling pathways, which are crucial for PA tumorigenesis and progression. Conclusion Our findings demonstrate that inhibition of HAT p300 by its selective inhibitor A-485 is a promising therapy for GHPA.

Objective To review experience regarding the treatment of prolactinomas by endoscopic endonasal surgery focusing on the association between presurgical dopamine agonist (DA) treatment and perioperative outcomes, surgical morbidities, endocrine outcomes, and pathological characteristics. Methods A single-center series of 290 cases was analyzed retrospectively and clinical data were collected. Intratumoral collagen content was assessed by Masson trichrome staining. Results Tenacious tumor consistency (27.8% vs 9.8%, P < .001) was more common in DA-pretreated patients compared with patients who underwent initial surgery. Moreover, DA-pretreated macroadenomas presented more intraoperative blood loss (200 [100-400] mL vs 175 [100-300] mL; P = .014), longer surgical duration (177 ± 95 minutes vs 154 ± 57 minutes; P = .043), and more surgical morbidities (19.4% vs 8.9%; P = .034). Additionally, DA-pretreated macroadenomas presented a higher collagen volume fraction than that of the initial surgery group (23.6 ± 2.2% vs 13.2 ± 2.1%; P = .001). Correlation analysis revealed a close correlation between collagen volume fraction and the cumulative dose of bromocriptine (BRC) in macroadenomas (r = 0.438, P < .001). Regarding endocrine outcomes, DA-pretreated microadenomas showed a lower proportion of initial remission compared with patients who underwent initial surgery (86.7% vs 100%, P = .047). Conclusion This study described increased surgical difficulty and inferior endocrine outcomes associated with tumor fibrosis secondary to presurgical BRC treatment in prolactinomas. Neurosurgeons should note that presurgical BRC treatment may render subsequent surgery more challenging.

Introduction: This study aims to develop a machine learning-based model integrating clinical and ophthalmic features to predict visual outcomes after transsphenoidal resection of sellar region tumors. Methods: Adult patients with optic chiasm compression by a sellar region tumor were examined to develop a model, and an independent retrospective cohort and a prospective cohort were used to validate our model. Predictors included demographic information, and ophthalmic and laboratory test results. We defined “recovery” as more than 5% for a p-value in mean deviation compared with the general population in the follow-up. Seven machine learning classifiers were employed, and the best-performing algorithm was selected. A decision curve analysis was used to assess the clinical usefulness of our model by estimating net benefit. We developed a nomogram based on essential features ranked by the SHAP score. Results: We included 159 patients (57.2% male), and the mean age was 42.3 years old. Among them, 96 patients were craniopharyngiomas and 63 patients were pituitary adenomas. Larger tumors (3.3 cm vs. 2.8 cm in tumor height) and craniopharyngiomas (73.6%) were associated with a worse prognosis (p < 0.001). Eyes with better outcomes were those with better visual field and thicker ganglion cell layer before operation. The ensemble model yielded the highest AUC of 0.911 [95% CI, 0.885–0.938], and the corresponding accuracy was 84.3%, with 0.863 in sensitivity and 0.820 in specificity. The model yielded AUCs of 0.861 and 0.843 in the two validation cohorts. Our model provided greater net benefit than the competing extremes of intervening in all or no patients in the decision curve analysis. A model explanation using SHAP score demonstrated that visual field, ganglion cell layer, tumor height, total thyroxine, and diagnosis were the most important features in predicting visual outcome. Conclusion: SHAP score can be a valuable resource for healthcare professionals in identifying patients with a higher risk of persistent visual deficit. The large-scale and prospective application of the proposed model would strengthen its clinical utility and universal applicability in practice.

Objective: Quality of Life (QoL) has been a multifactorial concerning issue in oncology. We aimed to inspect the pre-operative QoL among patients with craniopharyngioma and to explore the potential correlations between parameters of QoL and clinical indices. Subjects and methods: We enrolled a total of 109 patients with craniopharyngioma. We utilized Short Form 36 (SF-36), Symptom Check List-90, Generalized Anxiety Disorder Questionnaire scale (GAD7), Patient Health Questionnaire Depression (PHQ9) and Pittsburgh Sleep Quality Index to prospectively evaluated their QoL. [...] ABSTRACT Objective: Quality of Life (QoL) has been a multifactorial concerning issue in oncology. We aimed to inspect the pre-operative QoL among patients with craniopharyngioma and to explore the potential correlations between parameters of QoL and clinical indices. Subjects and methods: We enrolled a total of 109 patients with craniopharyngioma. We utilized Short Form 36 (SF-36), Symptom Check List-90, Generalized Anxiety Disorder Questionnaire scale (GAD7), Patient Health Questionnaire Depression (PHQ9) and Pittsburgh Sleep Quality Index to prospectively evaluated their QoL.