Introduction: Horner’s syndrome (HS) and shoulder syndrome (SS) are serious complications of thyroid surgery with neck dissection, caused by the injury of the oculosympathetic nerve pathway and of the spinal accessory nerve, respectively. Their concurrence is extremely rare. Aims: to report a peculiar case occurring in a 31-year-old woman after total open thyroidectomy with extended neck dissection and XI nerve skeletonization for metastatic thyroid cancer, and review literature data on diagnostic procedures, risk factors, treatment and outcome of HS and SS, caused by thyroid surgery performed through cervical route. Materials and Methods: PubMed database was searched using an ad hoc string. 78 studies were identified. After excluding cases operated by other than cervical route, or not reporting patient/treatment information of interest, 28 articles were included and analyzed for a total of 34 patients. 32 (94.1

OBJECTIVE:An endoscopic endonasal approach (EEA) is widely adopted for most craniopharyngioma surgeries due to its favorable clinical outcome. However, its role in recurrent tumors has not been fully assessed. The aim of this study was to analyze the surgical outcome of EEA in recurrent craniopharyngioma, assessing factors associated with radical resection and progression-free survival (PFS). METHODS:Consecutive patients with craniopharyngioma treated with surgery using an EEA at a single institution (1998-2024) were retrospectively reviewed. Those who met the inclusion criteria were divided into recurrent (prior treatment) and treatment-naive (no prior treatment) groups. Preoperative patient- and tumor-related features, surgical and clinical outcomes at follow-up, and complications were assessed and compared between the two groups. RESULTS:Overall, 126 patients (69 female, mean age 51.1 years) with craniopharyngioma treated using the EEA were included, 31 (24.6%) with recurrence and 95 (75.4%) who were treatment-naive. In the recurrent group, radical resection was achieved in 24 patients (77.4%), and the most common complication was CSF leakage (19.4%). No significant differences were observed for rates of resection and morbidity between the two groups. Radical resection of recurrent craniopharyngioma was associated with a previous transcranial surgical approach (p = 0.030) and a lower preoperative BMI (p = 0.014). In the overall cohort, longer PFS was correlated with no intraventricular extension (p = 0.004) and radical resection (p < 0.001). CONCLUSIONS:EEA proved to be a valid option for strictly selected patients with recurrent craniopharyngioma, with surgical and clinical outcome similar to those observed for treatment-naive patients. Radical resection and PFS were associated with both biological and technical factors, which should be taken into account in surgical planning and preoperative patient counseling.

Population-based studies overall report no excess mortality among patients with prolactinoma compared with the general population. However, since prolactinomas are clinically heterogeneous, mortality may not be uniform across data-driven patient profiles. We analyzed 3,378 adult prolactinoma cases (26,118 person-years) from the Surveillance, Epidemiology, and End Results database (2004–2022). Standardized mortality ratios (SMRs) were calculated using US life tables matched by age, sex, calendar year, race/ethnicity, and geography. Among 2,481 patients with available tumor size (18,097 person-years), unsupervised clustering (Fuzzy C-Means) based on age, tumor size, and sex defined patient profiles. Excess mortality ratios (EMRs) compared observed-to-expected mortality across profiles, adjusting for race, calendar year, surgery, and radiotherapy. Prolactinoma was associated with significant excess all-cause mortality (SMR 1.21, 95

It has been demonstrated that high expertise is crucial for pituitary surgery. Due to the low incidence of acromegaly, large data reporting the outcome of endoscopic surgery are limited. The objective was to evaluate the outcomes of acromegalic patients undergoing endoscopic surgery. This retrospective study included 822 consecutive acromegalic patients treated by endoscopic endonasal surgery by two expert French and Italian neurosurgical teams from 1998 to 2022. The primary outcome was postoperative endocrine remission. The secondary outcome was operative morbidity, including surgical complications and new endocrine deficits. Preoperative predictive factors of persistent postoperative hypersecretion were calculated. Mean follow-up was 46.3 months. The overall remission rate was 63%. Long-term remission was achieved in 202/230 (88%) enclosed microadenomas, 316/452 (70%) macroadenomas without obvious cavernous sinus invasion, and 3/140 (2%) obvious invasive tumors. Hematoma, nerve palsy, cerebrospinal fluid leak, meningitis and epistaxis occurred in 0.1%, 0.1%, 1%, 0.6% and 1.1% respectively. New anterior pituitary deficits and diabetes insipidus occurred in 25/822 (3%) and 30/822 (3.6%) of patients respectively. Age, obvious cavernous sinus invasion, and larger diameter were predictive of persistent hypersecretion in multivariate analysis. Recurrence of somatotroph hypersecretion occurred in 19/540 (4%) patients with early remission, with a mean time of 37.5 months. Endoscopic pituitary surgery is effective and safe for acromegaly, provided that patients are treated in tertiary reference centers. Remission rate is high in microadenomas. If normalized somatotroph axis is achieved after surgery, long-term remission can be expected in most patients.

Background/Objectives: Clivus metastases from distant neoplasms are uncommon occurrences both in clinical practice and the neurosurgical literature. Surgical management is debated, particularly about the role of surgery and the preferable approach. The aim of this study was to report our surgical experience and review the concerning literature. Methods: Our institutional registry was retrospectively reviewed, and patients who underwent surgical treatment for clival metastasis from 1998 to 2023 were included. A PRISMA systematic review of the literature was performed. Results: Four patients were enrolled, and all of them underwent an endoscopic endonasal approach (EEA). Three presented with cranial nerve (CN) VI palsy. The aim of surgery was biopsy in all cases. No complications were reported. Mean overall survival (OS) was 6 ± 1 months. The systematic review retrieved 27 papers reporting 39 patients who underwent the surgical treatment of clivus metastases. Most of them (79.5%) presented with CN palsies, and EEA was the preferred approach in 92.3% of the cases, to perform a biopsy in most patients (59%). Two hemorrhagic complications (5.1%) were reported, and the mean OS was 9.4 ± 5.6 months. Conclusions: Clival metastases are uncommonly observed, in most cases, during advanced stages of oncological disease. The aim of surgery should be the confirmation of diagnosis and symptomatic relief, balancing the risk–benefit ratio in a multidisciplinary context. EEA is the approach of choice, and it should be carried out in experienced tertiary skull base centers.

INTRODUCTION: The incidental finding of pituitary microadenomas (PmAs) is increasingly common due to the widespread use of MRI. To date, no comprehensive volumetric analyses of PmAs growth patterns have been conducted. A greater understanding of how these lesions progress could influence an array of management strategies, including frequency of imaging and the use of surgical versus conservative medical intervention. METHODS: Patients who underwent = 2 pituitary MRIs for suspected PmAs were identified retrospectively across 4 referral centers worldwide. Patient demographics, presenting symptoms, clinical variables, MRIs, and treatment course were collected and analyzed. RESULTS: A total of 447 patients (Male = 126; 28.2%) referred to the 4 centers from 2003 to 2022 were identified. Median age at first MRI was 43 years [IQR 32–54]. Median number of MRIs per patient was 3 [IQR 2–5] and median follow-up time was 55 months [IQR 29–100]. 300 PmAs (67.1%) were solid, 102 (22.8%) were cystic, 47 (10.5%) were uncertain, and 24 (5.4%) were mixed. At baseline, median suspected tumor volume was 45 mm 3 [15–103]. 77 patients (17.2%) presented with subclinical hyperpituitarism, most often hyperprolactinemia, while 67 (15.0%) experienced hypopituitarism such as hypogonadism, hypothyroidism, and growth hormone deficiency. During follow-up, new onset hyperpituitarism was detected in 20 patients (4.5%) along with hypopituitarism in 9 (2.0%). During the study period, 225 patients (50.3%) had no change in suspected PmA growth, 144 (32.2%) had a decreased size, and 101 (22.6%) had an increased size. 80 patients (17.9%) received medical therapy and 48 (10.7%) underwent transsphenoidal surgery. CONCLUSIONS: With the forthcoming volumetric analysis, we hope to gain further insights into predictors of long-term volumetric evolution of PmAs to improve patient management.

Context Cardiovascular diseases (CVDs) and cancer are the two main leading causes of death and disability worldwide. Suboptimal diet, poor in vegetables, fruits, legumes and whole grain, and rich in processed and red meat, refined grains, and added sugars, is a primary modifiable risk factor. Based on health, economic and ethical concerns, plant-based diets have progressively widespread worldwide. Objective This umbrella review aims at assessing the impact of animal-free and animal-products-free diets (A/APFDs) on the risk factors associated with the development of cardiometabolic diseases, cancer and their related mortalities. Data sources PubMed and Scopus were searched for reviews, systematic reviews, and meta-analyses published from 1st January 2000 to 31st June 2023, written in English and involving human subjects of all ages. Primary studies and reviews/meta-analyses based on interventional trials which used A/APFDs as a therapy for people with metabolic diseases were excluded. Data extraction The umbrella review approach was applied for data extraction and analysis. The revised AMSTAR-R 11-item tool was applied to assess the quality of reviews/meta-analyses. Results Overall, vegetarian and vegan diets are significantly associated with better lipid profile, glycemic control, body weight/BMI, inflammation, and lower risk of ischemic heart disease and cancer. Vegetarian diet is also associated with lower mortality from CVDs. On the other hand, no difference in the risk of developing gestational diabetes and hypertension were reported in pregnant women following vegetarian diets. Study quality was average. A key limitation is represented by the high heterogeneity of the study population in terms of sample size, demography, geographical origin, dietary patterns, and other lifestyle confounders. Conclusions Plant-based diets appear beneficial in reducing cardiometabolic risk factors, as well as CVDs, cancer risk and mortality. However, caution should be paid before broadly suggesting the adoption of A/AFPDs since the strength-of-evidence of study results is significantly limited by the large study heterogeneity alongside the potential risks associated with potentially restrictive regimens.

Objective: Cranial base chordomas are difficult lesions to treat. The endoscopic endonasal approach (EEA) takes advantage of the natural sinus corridor and may provide a less invasive approach for these midline tumors.Methods: Patients undergoing EEA for chordomas were selected from a database of more than 800 consecutive patients undergoing EEA at the University of Pittsburgh Medical Center and were retrospectively evaluated. Additionally, a systematic review of the literature of endoscopic endonasally resected chordomas was performed and compared with our personal experience.Results: Twenty patients (8 females and 12 males) underwent 26 endoscopic EEAs for cranial base chordomas. Eight chordomas (40%) were recurrent. Treatment of the 12 newly diagnosed chordomas included 8 total resections (66.7%), 2 near total resections (16.7%), and 2 subtotal resections (16.7%). Treatment of the 8 recurrent chordomas included 1 gross total resection (12.5%), 2 near total resections (25.0%), and 5 subtotal resections (62.5%). Two patients (10%) had recurrences, and 5 patients (25%) progressed during the mean follow-up period of 13 months (range, 1-45 months). Five patients (25%) underwent re-resection, 1 patient was lost to follow-up, and 1 patient died secondary to progression of disease. There was 1 intraoperative vascular complication with no sequelae. The cerebrospinal fluid leak rate was 25%, and there were no cases of bacterial meningitis. The incidence of a new permanent neurological complication was 5%. A systematic review of the literature yielded a total of 26 cases of chordomas resected via a completely endoscopic endonasal technique.Conclusion: Endoscopic endonasal resection of cranial base chordomas is safe once adequate experience is gained with the technique. This approach provides the potential for, at the least, similar resections compared with traditional cranial base approaches while potentially limiting morbidity.

Pituitary tumors present heterogeneous biochemical, clinico-radiological, and histological features. Although histologically benign, a non-negligible number of cases present an unpredictable aggressive behavior with local invasiveness, partial/complete resistance to treatment and/or recurrence after surgery, and, rarely, metastasize, overall leading to a significant increase of morbidity, and, thus, requiring skilled multidisciplinary management in referral Centers. Histopathological diagnosis is essential to stratify cancer patient risk and uniform follow-up among Centers. Classification of pituitary neoplasia is continuously evolving in relation to the increased knowledge of mechanisms underlying adenohypophyseal cell tumorigenesis, and the attempts of combining clinico-radiological, biochemical, intraoperative, histological, and molecular elements, with the aim of identifying aggressive forms through. An integrated standardized histopathological report has been proposed in 2019 by the European Pituitary Pathology Group, based on the indications of the 2017 WHO classification of pituitary tumors. The last edition of the WHO Classification of Central Nervous System Tumors and of Endocrine and Neuroendocrine Tumors brought substantial novelties: 1) the replacement of the term "adenoma" with "Pituitary Neuroendocrine Tumor" (PitNET), and of "carcinoma" with "metastatic PitNET," and the consequent ICD-11 recoding from benign to malignant disease; and 2) the pivotal role of lineage restricted pituitary transcription factors for histological typing and subtyping. However, this approach does not reflect the spectrum of tumor phenotypes based on hormone secretion, nor include molecular features. Efforts of interdisciplinary groups of pituitary experts should be strongly encouraged to better understand factors involved in PitNETs evolution and, consequently, standardize diagnosis and reporting based on the most recent knowledges, essential to stratify cancer patient risk and uniform follow-up among centers.

Somatotroph (GH) adenomas/PitNETs typically arise from adenohypophysis and are biochemically active, leading to acromegaly and gigantism. More rarely, they present with ectopic origin and do not present overt biochemical or clinical features (silent variants).Histopathological examination should consider the clinical and radiological background, and include multiple steps assessing tumor morphology, pituitary transcription factors (PTFs), hormone secretion, proliferation markers, granulation, and somatostatin receptors (STRs), aimed at depicting as better as possible tumor origin (in case of non-functioning and/or metastatic tumor), and clinical behavior, including response to treatment. GH-secreting tumors are part of the Pit-1 family tumors and can secrete GH only (pure somatotrophs) or co-secrete prolactin (mixed tumors; in this case, various histological subtypes have been identified). Each subtype presents unique radiological, biochemical, and clinical characteristic. Therefore, the integration of biochemical, clinical, radiological, and histopathological elements is fundamental for proper diagnosis and management of pituitary adenomas/PitNETs, to be performed in referral Centers. In more recent times, the importance of genetic and epigenetic evaluation in the characterization of pituitary tumors (i.e., early identification of aggressive variants) has been outlined by some large studies, with the intention of improving targeted treatments.

Spheno-orbital meningiomas are challenging invasive tumors, involving different cranial regions, requiring multiple surgical approaches and often with an unfavorable biological behavior characterized by multiple recurrences and possible escape from standard treatments.1 We present a case of a 57-year-old woman, already undergone a transcranial approach, an endoscopic transorbital surgery, and a radiosurgical treatment for a spheno-orbital meningioma. She presented a further tumoral recurrence, involving the orbit and the infratemporal and pterygopalatine fossa, and we proposed a combined fully endoscopic multistaged approach. The patient consented to the procedure and to the publication of his/her image. We adopted the endoscopic transorbital and the endoscopic transmaxillary-pterygoid corridors for the different portions of the tumor, followed by radiation therapy with carbon ions, achieving a large tumor resection with no progression at 12-month follow-up and without complications or neurological sequelae. This treatment strategy gave us the possibility to fully manage the tumoral extension with 2 innovative minimally invasive surgical procedures, which resulted well-tolerated and favored the prompt patient recovery and quality-of-life preservation, leaving the meningioma remnant to the external radiation therapy.2-6 Our case emphasizes the possibilities given by the endoscopic approaches to manage at 360° the multiregional extensions of a spheno-orbital meningioma, demonstrating how such direct and extracranial corridors could allow the surgeon to remove these tumors, with no brain retraction or manipulation and limited functional or neurological sequelae.7,8.

Introduction: The diagnosis of pituitary microprolactinomas is often obscured by relatively low levels of elevated prolactin compared to macroprolactinomas. This may lead to varying patterns of medical therapy versus observation. We sought to correlate prolactin levels in suspected microprolactinomas with tumor volumes and clinical outcomes.

Acromegaly is a rare disorder characterized by chronic hypersecretion of growth hormone (GH) and, consequently, of its mediator, insulin-like growth factor 1 (IGF-1), due in >95% of the cases to a GH-secreting pituitary adenoma (PA)/Pituitary Neuroendocrine Tumor (PitNET). PAs/PitNETs are extremely heterogeneous for clinical, biochemical, radiological, intra-operative, and histological features and, differently from other histologically benign lesions, can cause significant morbidity because of locally aggressive behavior, resistance/recurrence after treatment, and, although very rarely, metastasization. PAs/PitNETs' classification and nomenclature have consistently changed in the course of time, reflecting knowledges about their complex biology, with the aim of stratifying patient risk and, therefore, uniform therapeutic strategies. According to the last WHO Classification, based on pituitary transcription factors (i.e., Pit-1, TPIT, and SF-1), GH-secreting PAs/PitNETs pertain to the Pit-1-lineage. Several subtypes can be distinguished, i.e., somatotroph (sparsely and densely granulated), mixed (mammosomatotroph, mixed somatotroph-lactotroph, and acidophilic stem cell), and plurihormonal (mature and immature Pit-1 lineage), based on hormone staining at immunohistochemistry and granulation, with distinct clinical and radiological features. Unfortunately, this classification does not fully reflect the spectrum of tumor phenotypes, does not consider the presence of drug-target receptors (i.e., somatostatin), nor molecular features that, on the contrary, have been increasingly demonstrated to influence biological behavior. Therefore, efforts of pituitary expert of the various disciplines are still necessary to reach a more comprehensive and detailed PitNET stratification to improve patient care through precision medicine.

INTRODUCTION:Endoscopic endonasal approach (EEA) plays a central role in the treatment of GH-secreting pituitary adenomas (PAs)/pituitary neuroendocrine tumors (PitNETs), allowing to treat not only micro- or regular macro- PAs/PitNEts, but also more complex cases, otherwise requiring a transcranial or other open approaches. MATERIALS AND METHODS:All consecutive cases of GH-secreting PAs/PitNETs treated by EEA from May 1998 to June 2023 at our Institution were included. Patients clinical, bio-chemical, and neuroradiological features were considered, as well the surgical approach adopted for each case and its related complications. Surgical and endocrinological was determined at 3 months follow-up. RESULTS:Our series is composed of 356 patients (57.6% females, mean age: 47 ± 12.7 years old): 118 (33.1%) micro-, 180 (50.6%) regular macro- and 58 (16.3%) irregular/invasive PAs/PitNEts. Radical removal was achieved in 296 (83.1%) patients and biochemical control in 270 (75.8%) at 3 months follow-up. Better surgical results and higher hypersecretion remission rate were demonstrated for micro- and regular endo-/endosuprasellar PAs/PitNETs than for irregular ones (respectively p < 0.001 and p < 0.001). Higher complication and endocrinological function permanent worsening rates were observed in the group of tumors with a supradiaphragmatic extension. CONCLUSIONS:Our study confirmed the efficacy and safety of EEA in the short-term follow-up in patients with GH-secreting PAs/PitNETs. This approach has demonstrated to be highly versatile, allowing to tailor the surgery to each specific case, with the aim of obtaining the radical removal and consequently the biochemical remission with minimal complications, patients discomfort, or endocrinological sequelae in a large number of cases.

The diagnosis of pituitary microprolactinomas is often obscured by relatively low levels of elevated prolactin compared to macroprolactinomas. This may lead to varying patterns of medical therapy versus observation. We sought to correlate prolactin levels in suspected microprolactinomas with tumor volumes and clinical outcomes. This was a multicenter retrospective study of patients with pituitary microadenomas with baseline prolactin levels > 18ng/ml for males and > 30ng/ml for females. A linear-mixed model was used to depict changes in tumor volume over time. There were 65 patients with a mean tumor volume of 95.9mm3 and mean prolactin level of 59.4ng/ml. There were significantly higher prolactin levels in patients with tumors above the mean volume versus below (74.0 versus 53.4ng/ml, p = 0.027). 26 patients were observed, 31 were treated with anti-dopaminergic therapy, and 8 had surgery. There were significantly greater baseline prolactin levels for patients who were treated surgically (mean 86.4ng/ml) than those treated medically (mean 61.7 g/ml) or observed (mean 48.5ng/ml) (p = 0.02). Among the 26 patients who were surveilled, 13 patients demonstrated spontaneous tumor shrinkage, 12 remained stable, and 1 patient’s tumor grew but was lost to follow-up. Linear mixed modeling demonstrated a statistically significant rate of tumor shrinkage over time of 3.67mm3/year (p = 0.03). When analyzing patients who were observed versus those requiring surgery after initially being surveilled, there were significantly greater baseline PRL/volume ratios in surgical patients versus those observed (8.1 ng/ml/mm3 versus 2.4 ng/ml/mm3, p = 0.025). Suspected microprolactinomas may demonstrate more convincingly elevated prolactin levels when measuring over 95.9mm3. Tumors with baseline prolactin levels over 50ng/ml may be more inclined to undergo medical treatment. In tumors with levels below 50ng/ml, it may be reasonable to undergo surveillance as these tumors tend to spontaneously shrink over time. In tumors that are surveilled, an elevated baseline PRL/volume ratio of > 8 ng/ml/mm3 may be indicate serial tumor growth that may necessitate medical and/or surgical intervention.

Background Brain stroke is a rare, life-threatening condition associated with pituitary apoplexy (PA), resulting from direct arterial occlusion due to mechanical compression secondary to the sudden enlargement of the pituitary adenoma, or to vessel vasospasm, induced by tumor hemorrhage. Case report We report the case of a 64-year-old woman with PA complicated by bilateral anterior circulation stroke due to critical stenosis of both anterior cerebral arteries (ACA). Despite the quick surgical decompression and consequent blood flow restoration, the neurological conditions of the patient did not improve and she died 18 days later. Ten other cases of anterior circulation stroke due to PA were retrieved in a systematic review of literature. Clinical and neuroradiological features of these patients and treatment outcome were assessed to suggest the most proper management. Conclusion The onset of neurological symptoms suggestive for brain stroke in patients with PA requires performing an emergency Magnetic Resonance Imaging (MRI), including Diffusion-weighted and angiographic MR-sequences. The role of surgery in these cases is debated, however, transsphenoidal adenomectomy would permit us to decompress the ACA and restore blood flow in their territories. Although the prognosis of PA-induced anterior circulation stroke is generally poor, a timely diagnosis and treatment would be paramount for improving patient outcome.

Vaccine hesitancy (VH) has risen significantly during the COVID-19 pandemic, becoming a major global health concern. VH is characterized by the delay or refusal of vaccination despite its availability. Various frameworks have been developed to understand the complex factors influencing VH, with attitudes, beliefs, and external influences being the most significant. The surge in VH has reignited the debate on the best approach to address it: persuasive/ educational or coercive. Attwell and Hannah studied the political and social reasons behind the adoption of mandatory vaccination in four jurisdictions (Italy, France, Australia, and California) due to declining vaccine coverage below the safety threshold. However, these methods may foster parental disbeliefs and opposition to vaccination campaigns. To combat VH, it is crucial to systematically assess its determinants within specific contexts and population groups. Increasing awareness about vaccination benefits, engaging with social media, and employing tailored strategies can foster spontaneous adherence to vaccination programs, eliminating the need for coercive measures.

Introduction: Gross total resection (GTR), Biochemical Remission (BR) and restitution of a priorly disrupted hypothalamus pituitary axis (new improvement, IMP) are important factors in pituitary adenoma (PA) resection surgery. Prediction of these metrics using simple and preoperatively available data might help improve patient care and contribute to a more personalized medicine. Research question: This study aims to develop machine learning models predicting GTR, BR, and IMP in PA resection surgery, using preoperatively available data. Material and methods: With data from patients undergoing endoscopic transsphenoidal surgery for PAs machine learning models for prediction of GTR, BR and IMP were developed and externally validated. Development was carried out on a registry from Bologna, Italy while external validation was conducted using patient data from Zurich, Switzerland.Results: The model development cohort consisted of 1203 patients. GTR was achieved in 207 (17.2%, 945 (78.6%) missing), BR in 173 (14.4%, 992 (82.5%) missing) and IMP in 208 (17.3%, 167 (13.9%) missing) cases. In the external validation cohort 206 patients were included and GTR was achieved in 121 (58.7%, 32 (15.5%) missing), BR in 46 (22.3%, 145 (70.4%) missing) and IMP in 42 (20.4%, 7 (3.4%) missing) cases. The AUC at external validation amounted to 0.72 (95% CI: 0.63-0.80) for GTR, 0.69 (0.52-0.83) for BR, as well as 0.82 (0.76-0.89) for IMP.Discussion and conclusion: All models showed adequate generalizability, performing similarly in training and external validation, confirming the possible potentials of machine learning in helping to adapt surgical therapy to the individual patient.