Ageing and pituitary neuroendocrine tumours (PitNETs): from bench to bedside Dario De Alcubierre, Francesca Carbonara, Tiziana Feola, Francesca Gianno, Giuseppe Minniti, et al. Endocrine Related Cancer, 2026 Graphical Abstract Abstract The prevalence of pituitary neuroendocrine tumours (PitNETs) in elderly people (≥65 years old) is raising with life expectancy. Despite an increasing incidental detection on neuroimaging for unrelated conditions, a large majority are macrotumours (≥1 cm) and mass effects are frequent, in particular visual defects. Clinically non-functioning PitNETs are the most prevalent (about 75%), and a majority are gonadotrophs. The clinical presentation of functioning PitNETs differ from younger patients and include somatotroph tumours – often intrasellar with mild acromegaly, prolactinomas – often large and invasive, and rare corticotroph and uncommon thyrotroph tumours. Such epidemiological characteristics likely reflect different biological features as compared with PitNETs diagnosed in younger patients. Epigenetic alterations are more frequent than mutations, whereas cell senescence and age-related changes in immune surveillance and feedback mechanisms from ageing target organs may play an underestimated role. Endocrinological changes associated with ageing and concomitant pathological conditions should be considered as relevant confounding factors for diagnosis. In particular, ocular diseases may mask visual defects, progressive symptoms of hypopituitarism may be misinterpreted as ageing, and peripheral physiological (menopause) or pathological dysfunction or drugs given for other diseases can alter pituitary hormone secretion. Mild hypersecretion should be searched for in clinically non-functioning cases, as it may significantly impact on clinical management. Multidisciplinary evaluation is necessary to define personalized therapeutic goals, and where indicated, surgery should be performed by experienced pituitary surgeons. The development of innovative diagnostic and prognostic markers would usefully support the clinical management and follow-up of PitNETs in elderly patients.
Life-Threatening Radiation Necrosis After Complete Response to Pembrolizumab in a Patient With a Metastatic Silent PIT1 Pituitary Neuroendocrine Tumor (PitNET) Dario De Alcubierre, Tiziana Feola, Francesca Gianno, Monica Verrico, Francesca Carbonara, et al. Journal of Immunotherapy, 2026 Metastatic pituitary neuroendocrine tumors (metPitNETs) are rare neoplasms with limited therapeutic options. Temozolomide is the first-line therapy, but primary or secondary resistance frequently occurs. Immune checkpoint inhibitors (ICIs) are emerging as a promising second-line option; however, clinical experience remains limited. We report the long-term follow-up of a 62-year-old male patient who received pembrolizumab (PBZ) treatment for a silent metPitNET derived from the PIT1 lineage after multiple surgical and radiation therapies and temozolomide failure. PBZ was proposed based on extensive PD‐L1 expression by tumor cells. A remarkable clinical, radiologic, and metabolic response was soon observed, progressively leading to complete disease remission after 21 months of treatment, with moderate immune-related adverse events. However, an unexpected rapid neurological deterioration occurred, due to the progression of a pseudotumoral temporal radionecrosis surrounded by an impressive vasogenic oedema, requiring emergency neurosurgery 7 weeks after PBZ withdrawal. The temporal mass had progressively developed on a previous small temporal metastasis treated through stereotactic radiosurgery, the corresponding area was hypometabolic at 18 FDG PET-CT imaging, and histopathologic examination confirmed extensive radionecrosis and the absence of residual tumor cells. This is the first documented complete response to ICI in a PIT1-derived metPitNET. However, this remarkable response was complicated by the severe evolution of a brain radionecrosis, probably favoured by long-term PBZ. This case underscores the need for multidisciplinary expertise to differentiate treatment effects from neoplastic progression and to carefully follow-up the patients for potentially severe late treatment-related complications. It also questions the optimal duration of treatment in responsive cases.
Perioperative Management of Chronic Subdural Hematoma Under Antithrombotic Therapy: A Multicenter Analysis of 679 Patients Giuseppe Corazzelli, Maria Rosaria Scala, Luigi Sigona, Ioana Maftei, Ciro Mastantuoni, et al. Neurosurgery, 2026 BACKGROUND AND OBJECTIVES: Management of chronic subdural hematoma (cSDH) in elderly patients receiving antithrombotic therapy remains heterogeneous, and surgical evacuation is often delayed allowing partial pharmacological washout despite limited supporting evidence. The aim of this study was to determine whether a structured perioperative pathway permits safe evacuation of cSDH as soon as logistically feasible, without awaiting drug washout, and to evaluate differences in recurrence probability and timing across antiplatelet, anticoagulant, and nonantithrombotic cohorts. METHODS: A multicenter retrospective analysis was conducted on consecutive elderly patients treated through a shared perioperative management. Patients were stratified into antiplatelet therapy (Group A, n = 199), anticoagulant therapy (Group B, n = 254), and no antithrombotic therapy (Group C, n = 226). Early recurrence rates were compared using predefined ±10% equivalence margins. Independent predictors of recurrence probability were identified using multivariate logistic regression analysis, and determinants of recurrence timing were assessed with Cox proportional hazards model. RESULTS: Early recurrence occurred in 9.0% of Group A, 11.8% of Group B, and 13.7% of Group C, with no significant differences among groups. Equivalence testing confirmed that recurrence rates met predefined equivalence criteria across all pairwise comparisons. Mean time to recurrence differed significantly ( P = .023), with earlier recurrence in antiplatelet-treated patients. In the multivariate logistic regression model, postoperative length of stay was the only independent predictor of recurrence probability ( P < .001). In the Cox model, antiplatelet therapy (hazard ratio 3.387, P < .001) and a history of stroke (hazard ratio 2.726, P = .034) independently influenced recurrence timing, whereas pharmacological status did not increase recurrence incidence. Complication rates were comparable across groups, and no thromboembolic events were observed. CONCLUSION: A shared perioperative pathway allowed cSDH evacuation as soon as logistically feasible while maintaining comparable early recurrence rates across antiplatelet, anticoagulant, and nonantithrombotic groups, despite differences in time to recurrence. Distinct predictors of recurrence probability and timing support the feasibility and clinical relevance of immediate surgical treatment within a coordinated perioperative framework.
Ion Channels in Glioma Malignancy Luigi Catacuzzeno, Luigi Sforna, Vincenzo Esposito, Cristina Limatola, Fabio Franciolini Reviews of Physiology Biochemistry and Pharmacology, 2021
Glioblastoma Multiforme: Tumor Recurrence Francesco Fabbiano, Jacopo Scaggiante, Andrea Wlderk, Alessandro D’Elia, Vincenzo Esposito, et al. Imaging Gliomas After Treatment A Case Based Atlas Second Edition, 2019
Prognostic significance of serial postoperative EEG in extratemporal lobe epilepsy surgery Bollettino Lega Italiana Contro L Epilessia, 2013
Surgery after intracranial investigation with subdural electrodes in patients with drug-resistant focal epilepsy: Outcome and complications Bollettino Lega Italiana Contro L Epilessia, 2013
Memory outcome two years after anterior temporal lobectomy in patients with drug-resistant epilepsy Bollettino Lega Italiana Contro L Epilessia, 2008
Changes in depression, anxiety, anger, and personality after resective surgery for drug-resistant temporal lobe epilepsy: A 2-year follow-up study Bollettino Lega Italiana Contro L Epilessia, 2008
A semiautomatic procedure for sequential neuroimage-fusion to localize subdural electrodes in presurgical evaluation of patients with drug-resistant focal epilepsy Bollettino Lega Italiana Contro L Epilessia, 2008
Lateralizing value of memory tests in drug-resistant temporal lobe epilepsy Bollettino Lega Italiana Contro L Epilessia, 2005
Drug-resistant seizures originating in the posterior cortex: Intracranial investigations by subdurally implanted electrodes Bollettino Lega Italiana Contro L Epilessia, 2005
Temporal lobe epilepsy surgery: Different surgical strategies after a non-invasive diagnostic protocol Bollettino Lega Italiana Contro L Epilessia, 2005
Localizing value of TIRDA (Temporal Intermittent Rhythmical Delta Activity): Video-EEG study in patients with drug-resistant partial epilepsy Bollettino Lega Italiana Contro L Epilessia, 2002
"Negative" ictal phenomena in temporal lobe epilepsy: Prominent involvement of neo-cortical structures? Bollettino Lega Italiana Contro L Epilessia, 2002
Memory functioning study in patients affected by drug resistant temporal lobe epilepsy classified in "mesial", "mesio-lateral" and "lateral" subtypes Bollettino Lega Italiana Contro L Epilessia, 2002
Assessing personality and psychopathology in patients affected by drug-resistant temporal epilepsy evaluated for epilepsy surgery: Preliminary results Bollettino Lega Italiana Contro L Epilessia, 2002
Non invasive pre-surgical evaluation and surgery in drug-resistant temporal lobe epilepsy Bollettino Lega Italiana Contro L Epilessia, 2002
Localizing value of Localized Subclinical Ictal Discharges (LOSID): A Video-EEG study in drug-resistant temporal lobe epilepsy Bollettino Lega Italiana Contro L Epilessia, 2001
Memory functioning study in patients affected by drug resistant temporal lobe epilepsy classified in "mesial" and "lateral" subtypes Bollettino Lega Italiana Contro L Epilessia, 2001
Assessing personality and psychopathology in patients affected by drug-resistant partial epilepsy evaluated for epilepsy surgery Bollettino Lega Italiana Contro L Epilessia, 2001
"Quality of life" evaluation in patients affected by drug-resistant partial epilepsy before and after epilepsy surgery Bollettino Lega Italiana Contro L Epilessia, 2001
Epilepsy surgery unit of neuromed institute (Pozzilli): Preliminary results after two years of experience Bollettino Lega Italiana Contro L Epilessia, 2001
Multicentric cerebral gliomas: Case report Nuova Rivista Di Neurologia, 1998
P-043. IGF-I measurement in post-operative evaluation of patients with tumours of the sellar region Endocrinology and Metabolism Supplement, 1997
An experimental contribution on the temporal lobe and epilepsy: The role of diffuse aspecific systems Bollettino Lega Italiana Contro L Epilessia, 1996
Prognostic value of scalp EEG ictal patterns in epilepsy surgery of hippocampal sclerosis G Di Gennaro, A Romigi, PP Quarato, A Mascia, A D’Aniello, C Panzini, ... Neurological Sciences 45 (10), 5003-5009 , 2024 2024 Citations: 4
Hidden intra-meatal CSF fistula related to VP shunt as a cause for fatal tension pneumocephalus after vestibular schwannoma resection P di Russo, R Morace, T Vangelista, N Gorgoglione, M De Angelis, ... British Journal of Neurosurgery 38 (4), 1010-1015 , 2024 2024 Citations: 1
The anterior sylvian point as a reliable landmark for the anterior temporal lobectomy in mesial temporal lobe epilepsy: technical note, case series, and cadaveric dissection A Fava, SV Lisi, L Mauro, R Morace, M Ciavarro, N Gorgoglione, ... Frontiers in Medicine 11, 1352321 , 2024 2024 Citations: 3
Posterolateral approaches to the thoracic spine for calcific disc herniation: is wider exposure always better? G Corazzelli, G Di Noto, A Ciardo, M Colangelo, S Corvino, S Leonetti, ... Acta Neurochirurgica 166 (1), 267 , 2024 2024 Citations: 4
Parasagittal meningiomas: The impact of sinus opening and grade of resection on clinical outcome and recurrence in a consecutive series of patients G Petrella, A Piazza, A Fava, N Gorgoglione, M De Angelis, T Vangelista, ... World Neurosurgery 186, e683-e693 , 2024 2024 Citations: 3
A study of alternative TrkA splicing identifies TrkAIII as a novel potentially targetable participant in PitNET progression M Sbaffone, ML Jaffrain-Rea, L Cappabianca, F Carbonara, F Gianno, ... Biology 13 (3), 171 , 2024 2024 Citations: 4
Clinical and molecular characteristics of gonadotroph pituitary tumors according to the WHO Classification F Carbonara, T Feola, F Gianno, MA Polidoro, RM Di Crescenzo, ... Endocrine Pathology 35 (1), 1-13 , 2024 2024 Citations: 6
Outcome of epilepsy surgery in MRI-negative patients without histopathologic abnormalities in the resected tissue MW Sanders, I Van der Wolf, FE Jansen, E Aronica, C Helmstaedter, ... Neurology 102 (4), e208007 , 2024 2024 Citations: 37
The “state of the art” of intraoperative neurophysiological monitoring: An Italian neurosurgical survey RA Ricciuti, F Mancini, G Guzzi, D Marruzzo, A Dario, A Della Puppa, ... Brain and Spine 4, 102796 , 2024 2024 Citations: 3
Anatomical landmarks during high-magnification microsurgery for a safe and effective resection of high-grade gliomas: how i do it A Fava, P di Russo, R Morace, V Esposito Acta neurochirurgica 165 (12), 4235-4240 , 2023 2023 Citations: 4
Identifying brain tumor patients’ subtypes based on pre-diagnostic history and clinical characteristics: a pilot hierarchical clustering and association analysis S Esposito, E Ruggiero, A Di Castelnuovo, S Costanzo, M Bonaccio, ... Frontiers in Oncology 13, 1276253 , 2023 2023
The impact of COVID-19 pandemic on surgical neuro-oncology: A survey from the Italian society of neurosurgery (SINch) L Zanin, T Ius, PP Panciani, F Esposito, A Gori, MM Fontanella, ... World Neurosurgery: X 20, 100233 , 2023 2023 Citations: 1
Long-term treatment outcomes of temozolomide-based chemoradiation in patients with adult-type diffuse IDH-mutant grade 2 astrocytoma G Minniti, S Paolini, M Antonelli, F Gianno, P Tini, G Lanzetta, A Arcella, ... Journal of Neuro-Oncology 164 (2), 331-339 , 2023 2023 Citations: 10
Surgical management of Glioma Grade 4: technical update from the neuro-oncology section of the Italian Society of Neurosurgery (SINch®): a systematic review T Ius, G Sabatino, PP Panciani, MM Fontanella, R Rudà, A Castellano, ... Journal of Neuro-oncology 162 (2), 267-293 , 2023 2023 Citations: 42
Feasibility of clinical target volume reduction for glioblastoma treated with standard chemoradiation based on patterns of failure analysis G Minniti, P Tini, M Giraffa, L Capone, G Raza, I Russo, E Cinelli, ... Radiotherapy and Oncology 181, 109435 , 2023 2023 Citations: 43
Key role of microsurgical dissections on cadaveric specimens in neurosurgical training: setting up a new research anatomical laboratory and defining neuroanatomical milestones A Fava, N Gorgoglione, M De Angelis, V Esposito, P Di Russo Frontiers in Surgery 10, 1145881 , 2023 2023 Citations: 15
Food processing and risk of central nervous system tumours: A preliminary case–control analysis from the MEditerranean DIet in relation to CancEr of brAin (MEDICEA) study S Esposito, M Bonaccio, E Ruggiero, S Costanzo, A Di Castelnuovo, ... Clinical Nutrition 42 (2), 93-101 , 2023 2023 Citations: 21
The Dietary Intake of Polyphenols Is Associated with a Lower Risk of Severe Lumbar Spinal Stenosis: A Case-Control Analysis from the PREFACE Study E Ruggiero, S Esposito, S Costanzo, A Di Castelnuovo, M Storto, ... Nutrients 14 (24), 5229 , 2022 2022
Sleep macrostructure and cyclic alternating pattern in patients who underwent surgery for hippocampal sclerosis: A prospective controlled polysomnographic study A Romigi, A D'Aniello, M Caccamo, F Testa, G Vitrani, L Grammaldo, ... Sleep Medicine 100, 419-426 , 2022 2022 Citations: 7
Immunotherapy for aggressive and metastatic pituitary neuroendocrine tumors (PitNETs): state-of-the art T Feola, F Carbonara, M Verrico, RM Di Crescenzo, F Gianno, ... Cancers 14 (17), 4093 , 2022 2022 Citations: 34
MOST CITED SCHOLAR PUBLICATIONS
Single-fraction versus multifraction (3× 9 Gy) stereotactic radiosurgery for large (> 2 cm) brain metastases: a comparative analysis of local control and risk of radiation … G Minniti, C Scaringi, S Paolini, G Lanzetta, A Romano, F Cicone, M Osti, ... International Journal of Radiation Oncology* Biology* Physics 95 (4), 1142-1148 , 2016 2016 Citations: 551
Seizure outcome and use of antiepileptic drugs after epilepsy surgery according to histopathological diagnosis: a retrospective multicentre cohort study HJ Lamberink, WM Otte, I Blümcke, KPJ Braun, M Aichholzer, I Amorim, ... The Lancet Neurology 19 (9), 748-757 , 2020 2020 Citations: 387
Anomalous levels of Cl − transporters in the hippocampal subiculum from temporal lobe epilepsy patients make GABA excitatory E Palma, M Amici, F Sobrero, G Spinelli, S Di Angelantonio, D Ragozzino, ... Proceedings of the National Academy of Sciences 103 (22), 8465-8468 , 2006 2006 Citations: 372
Long-term follow-up of intramedullary spinal cord tumors: a series of 202 cases A Raco, V Esposito, J Lenzi, M Piccirilli, R Delfini, G Cantore Neurosurgery 56 (5), 972-981 , 2005 2005 Citations: 365
Autophagy induction impairs migration and invasion by reversing EMT in glioblastoma cells M Catalano, G D'Alessandro, F Lepore, M Corazzari, S Caldarola, ... Molecular oncology 9 (8), 1612-1625 , 2015 2015 Citations: 328
Multidose stereotactic radiosurgery (9 Gy× 3) of the postoperative resection cavity for treatment of large brain metastases G Minniti, V Esposito, E Clarke, C Scaringi, G Lanzetta, M Salvati, A Raco, ... International Journal of Radiation Oncology* Biology* Physics 86 (4), 623-629 , 2013 2013 Citations: 258
Treatment of trigeminal neuralgia by thermocoagulation, glycerolization, and percutaneous compression of the gasserian ganglion and/or retrogasserian rootlets: long-term … B Fraioli, V Esposito, B Guidetti, G Cruccu, M Manfredi Neurosurgery 24 (2), 239-245 , 1989 1989 Citations: 233
Somatotopy in the basal ganglia: experimental and clinical evidence for segregated sensorimotor channels P Romanelli, V Esposito, DW Schaal, G Heit Brain research reviews 48 (1), 112-128 , 2005 2005 Citations: 218
Alpha, beta and gamma electrocorticographic rhythms in somatosensory, motor, premotor and prefrontal cortical areas differ in movement execution and observation in humans C Babiloni, C Del Percio, F Vecchio, F Sebastiano, G Di Gennaro, ... Clinical Neurophysiology 127 (1), 641-654 , 2016 2016 Citations: 196
The long‐term efficacy of conventional radiotherapy in patients with GH‐secreting pituitary adenomas G Minniti, ML Jaffrain‐Rea, M Osti, V Esposito, A Santoro, F Solda, ... Clinical endocrinology 62 (2), 210-216 , 2005 2005 Citations: 177
Expression of aryl hydrocarbon receptor (AHR) and AHR-interacting protein in pituitary adenomas: pathological and clinical implications ML Jaffrain-Rea, M Angelini, D Gargano, MA Tichomirowa, AF Daly, ... Endocrine-related cancer 16 (3), 1029-1043 , 2009 2009 Citations: 173
A critical reappraisal of MIB-1 labelling index significance in a large series of pituitary tumours: secreting versus non-secreting adenomas. ML Jaffrain-Rea, D Di Stefano, G Minniti, V Esposito, A Bultrini, E Ferretti, ... Endocrine-related cancer 9 (2), 103-113 , 2002 2002 Citations: 160
Transmaxillosphenoidal approach to tumors invading the medial compartment of the cavernous sinus B Fraioli, V Esposito, A Santoro, G Iannetti, R Giuffrè, G Cantore Journal of neurosurgery 82 (1), 63-69 , 1995 1995 Citations: 160
Enriched environment reduces glioma growth through immune and non-immune mechanisms in mice S Garofalo, G D’Alessandro, G Chece, F Brau, L Maggi, A Rosa, A Porzia, ... Nature Communications 6 (1), 6623 , 2015 2015 Citations: 156
Ictal heart rate increase precedes EEG discharge in drug-resistant mesial temporal lobe seizures G Di Gennaro, PP Quarato, F Sebastiano, V Esposito, P Onorati, ... Clinical neurophysiology 115 (5), 1169-1177 , 2004 2004 Citations: 151
The role of fractionated radiotherapy and radiosurgery in the management of patients with craniopharyngioma G Minniti, V Esposito, M Amichetti, R Maurizi Enrici Neurosurgical review 32 (2), 125-132 , 2009 2009 Citations: 144
Long-term follow-up results of postoperative radiation therapy for Cushing’s disease G Minniti, M Osti, ML Jaffrain-Rea, V Esposito, G Cantore, R Maurizi Enrici Journal of neuro-oncology 84 (1), 79-84 , 2007 2007 Citations: 143
Correlation between O 6 -methylguanine-DNA methyltransferase and survival in elderly patients with glioblastoma treated with radiotherapy plus concomitant and … G Minniti, M Salvati, A Arcella, F Buttarelli, A D’Elia, G Lanzetta, ... Journal of neuro-oncology 102 (2), 311-316 , 2011 2011 Citations: 135
Stereotactic radiosurgery combined with nivolumab or Ipilimumab for patients with melanoma brain metastases: evaluation of brain control and toxicity G Minniti, D Anzellini, C Reverberi, GCA Cappellini, L Marchetti, ... Journal for immunotherapy of cancer 7 (1), 102 , 2019 2019 Citations: 134
Diagnosis and management of pituitary tumours in the elderly: a review based on personal experience and evidence of literature G Minniti, V Esposito, M Piccirilli, A Fratticci, A Santoro, ML Jaffrain-Rea European journal of endocrinology 153 (6), 723-735 , 2005 2005 Citations: 132