Sáez-Alegre, Miguel

OBJECTIVE Nonfunctioning pituitary adenomas (NFPAs) often present with associated mild hyperprolactinemia, described in literature as "stalk effect." The presence of preoperative hyperprolactinemia caused by tumor compression of the pituitary stalk and endocrinological outcomes has been noted; however, a detailed investigation on the impact on perioperative endocrinological outcome is lacking. The authors aimed to determine whether elevated preoperative serum prolactin concentrations are associated with increased risk of perioperative pituitary dysfunction in patients with NFPAs undergoing endonasal transsphenoidal surgery (ETS). METHODS The authors conducted a single-center retrospective cohort study of patients who underwent ETS for NFPAs between January 2013 and April 2023. Patients were divided into two groups based on preoperative prolactin concentrations: normal or hyperprolactinemic (prolactin values above upper limit of reference range, adjusted for sex). Outcomes included perioperative endocrinological function and surgical outcomes. Multivariable analysis was conducted to identify factors associated with perioperative endocrinological function outcomes. RESULTS Of 244 patients (140 [57%] males; median age 59 years) with a median follow-up of 65 months, 131 (54%) had hyperprolactinemia. Compared with patients with normal preoperative prolactin levels (n = 113), the hyperprolactinemia group had similar tumor size (median diameter 2.5 cm vs 2.3 cm, p = 0.102) but higher rates of cavernous sinus invasion (99% vs 91%, p = 0.035), pituitary stalk deviation (95% vs 74%, p = 0.001), stalk bending (14% vs 1%, p = 0.001), preoperative secondary hypothyroidism (39% vs 22%, p = 0.005), and adrenal insufficiency (AI; 34% vs 22%, p = 0.048). Postoperatively, the hyperprolactinemia group showed higher rates of new secondary hypothyroidism (16% vs 7%, p = 0.048) and new permanent AI (16% vs 6%, p = 0.046). Multivariable analysis revealed preoperative high prolactin as an independent predictor of preoperative secondary hypothyroidism (OR 1.83, 95% CI 1.17–3.44; p = 0.046) and its postoperative deterioration (OR 2.65, 95% CI 1.02–7.69; p = 0.042). Maximum tumor diameter was also a significant predictor of various endocrinological dysfunctions both pre- and postoperatively. CONCLUSIONS Preoperative hyperprolactinemia in patients with NFPA is associated with higher risks of specific perioperative endocrinological dysfunction and pronounced pituitary stalk deviation. These findings highlight the utility of preoperative prolactin levels as a biomarker for predicting postoperative endocrinological outcomes, potentially enhancing risk assessment and guiding personalized perioperative management.

OBJECTIVE Patients with growth hormone (GH)–secreting pituitary adenomas (PAs) experience various symptoms and comorbidities, which can ultimately lead to increased mortality. This study aimed to develop and validate a machine learning (ML) model for predicting long-term outcomes in patients with GH-secreting PAs following endonasal transsphenoidal surgery (ETS). METHODS The authors conducted a retrospective three-institution cohort study that included patients with GH-secreting PAs treated with ETS between 2013 and 2023. Clinical, radiological, and biochemical data were collected. The main outcome of interest was the intervention-free rate (IFR) after primary ETS. Supervised ML algorithms, including decision trees and random forests, were developed to predict the IFR. Model performance was evaluated using area under the receiver operating characteristic curve (AUROC) and Shapley Additive Explanations (SHAP) values. RESULTS The median follow-up for 100 patients with GH-secreting PAs (53% female) was 64 months (range 1–130 months). Additional intervention for persistent or recurrent acromegaly was required in 32% of patients. Following primary ETS alone, the 3-year IFR was 70% and the 5-year IFR was 67%. Multiple ML models were developed and evaluated using AUROCs. The decision tree analysis achieved an accuracy of 81% and emphasized the importance of both gross-total resection (GTR) and patient age in determining the long-term IFR. To better understand the factors that contributed to model performance, SHAP analysis was applied to the best-performing model. The SHAP dependence plots showed that key factors associated with a longer IFR included tumor size < 9 mm, GTR, patient age > 65 years, and Knosp grade 0. CONCLUSIONS This ML model offers a more nuanced and potentially more accurate approach to identify patients more likely to develop recurrent or persistent acromegaly following primary ETS and require additional treatment. Following external validation, this ML model could improve personalized treatment planning and follow-up strategies and enhance patient care and resource allocation in clinical practice.

OBJECTIVE The principal tenet of minimally invasive neurosurgery is to limit approach-related tissue trauma, and a major assumption is that shorter incisions and smaller openings, in addition to protecting the brain, also have some perceptible benefits for the patient. This study tests the assumption of patient benefit and tries to define its significance. METHODS Procedures that fit the inclusion criteria of minimally invasive transcranial "keyhole" surgery were sought in the principal investigator’s archives. Each case was then paired with a classic procedure performed within the study time frame by the two senior authors, matched for pathology, size, location, and complexity. These pairs were then compared using a statistical tool (i.e., the Wilcoxon signed-rank test) designed for matched samples. Differences in estimated blood loss, duration of surgery, and length of hospital stay were examined. The narcotic needs during hospitalization were also examined as morphine milligram equivalent (MME). RESULTS Ninety patients were included in this study, evenly split between the minimally invasive surgery (MIS) and classic cohorts. Comparison of the 45 pairs showed no significant difference in estimated blood loss, though the operative times favored the MIS cohort significantly (mean ± SEM 310 ± 17 minutes vs 383 ± 24 minutes, p = 0.02). The length of stay was shorter for MIS, but the difference reached statistical significance only when cases with complications were excluded. The most important finding was that significantly less narcotic was needed during hospitalization in the MIS cohort (83 ± 15 MME vs 257 ± 47 MME). CONCLUSIONS The large difference in narcotic needs points to enhanced recovery from MIS techniques. While the difference in operative time did not lead to significantly shorter hospital stays, data suggest that minimally invasive technique may benefit the patient during recovery. This inspires further investigations to define the potentially positive impact on hospital and healthcare systems.

OBJECTIVE In this study, the authors aimed to establish a supervised machine learning (ML) model based on multiple tree-based algorithms to predict long-term biochemical outcomes and intervention-free survival (IFS) after endonasal transsphenoidal surgery (ETS) in patients with Cushing’s disease (CD). METHODS The medical records of patients who underwent ETS for CD between 2013 and 2023 were reviewed. Data were collected on the patient’s baseline characteristics, intervention details, histopathology, surgical outcomes, and postoperative endocrine functions. The study’s primary outcome was IFS, and the therapeutic outcomes were labeled as "under control" or "treatment failure," depending on whether additional therapeutic interventions after primary ETS were required. The decision tree and random forest classifiers were trained and tested to predict long-term IFS based on unseen data, using an 80/20 cohort split. RESULTS Data from 150 patients, with a median follow-up period of 56 months, were extracted. In the cohort, 42 (28%) patients required additional intervention for persistent or recurrent CD. Consequently, the IFS rates following ETS alone were 83% at 3 years and 78% at 5 years. Multivariable Cox proportional hazards analysis demonstrated that a smaller tumor diameter that could be detected by MRI (hazard ratio 0.95, 95% CI 0.90–0.99; p = 0.047) was significantly associated with greater IFS. However, the lack of tumor detection on MRI was a poor predictor. The ML-based model using a decision tree model displayed 91% accuracy (95% CI 0.70–0.94, sensitivity 87.0%, specificity 89.0%) in predicting IFS in the unseen test dataset. Random forest analysis revealed that tumor size (mean minimal depth 1.67), Knosp grade (1.75), patient age (1.80), and BMI (1.99) were the four most significant predictors of long-term IFS. CONCLUSIONS The ML algorithm could predict long-term postoperative endocrinological remission in CD with high accuracy, indicating that prognosis may vary not only with previously reported factors such as tumor size, Knosp grade, gross-total resection, and patient age but also with BMI. The decision tree flowchart could potentially stratify patients with CD before ETS, allowing for the selection of personalized treatment options and thereby assisting in determining treatment plans for these patients. This ML model may lead to a deeper understanding of the complex mechanisms of CD by uncovering patterns embedded within the data.

BACKGROUND AND OBJECTIVES: The lateral transorbital approach (LTOA) has gained increased recognition, but there is still a paucity of data on its effectiveness and advantages compared with the LTOA with lateral orbitotomy, herein denoted as the lateral orbital wall approach (LOWA). The aim of this study was to provide an anatomical reappraisal and the authors' clinical experience to compare the 2 approaches to the orbit and middle cranial fossa (MCF). METHODS: Eight latex-injected cadaveric specimens were used to perform LTOA and LOWA. The operative depth of each approach to key anatomical landmarks was measured. Fifty high-resolution computed tomography studies were reviewed to calculate the operative angles. We reviewed 40 consecutive cases treated with LTOA and LOWA at our institution. RESULTS: Compared with the LTOA, the LOWA provided shorter operative depths to the optic foramen ( P < .05), foramen ovale ( P < .05), and to the junction eyeball-cranial nerve II ( P = .13). It also offered better access to the anterior aspect of the orbit with less orbital content retraction. The LTOA and LOWA provided different operative angles to key anatomical landmarks in the orbit and MCF ( P < .05). In our chart review, 31 patients underwent the LTOA, whereas 9 underwent the LOWA to treat orbital and MCF lesions. Patients undergoing LOWA experienced postoperative complications related to periorbital nerves, such as frontalis palsy (n = 1) and supraorbital neuralgia (n = 1). Patients undergoing LTOA were more prone to complications associated with intraorbital manipulation (n = 4), including diplopia and ptosis. CONCLUSION: Our data suggest that the LTOA can be an effective surgical strategy for addressing orbital apex and MCF lesions. Although the LOWA provides access to the aforementioned areas, it may be more suitable for anterior orbital lesions that require direct access with wider entry exposure and extensive orbital content manipulation.