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Introduction: First-generation somatostatin receptor ligands (fg-SRLs) are the cornerstone of acromegaly treatment. Additional benefits were shown using high dose (HD) or high frequency (HF), relatively short-term regimens. Although several predictors of response to standard dose (SD)-fg-SRLs were reported, outcome biomarkers for HF administration are not yet available. Here, we aimed to identify predictors of response to long-term HF-fg-SRLs., Patients and Methods: A retrospective study was performed on 102 patients, treated with Lanreotide. Patients not controlled at 12 months of SD-Lanreotide (120 mg/28 days) were switched to HF-Lanreotide (120 mg/21 days) for additional 12 months., Results: Twenty-eight patients were controlled at 6 months of SD-Lanreotide (27.4%); 35 patients were controlled at 12 months of treatment (34.3%). Out of 67 patients treated with HF- Lanreotide, 18 (26.9%) were controlled at 6 months of treatment and remained controlled until 12 months. Both during SD and HF-Lanreotide administrations, IGF-I levels were reduced during the first six months of treatment (p < 0.001), without further significant reduction between 6 and 12 months of therapy. Response at 12 months of SD-Lanreotide was predicted by IGF-I reached at six months of SD-Lanreotide (p = 0.024). Response at 12 months of HF-Lanreotide treatment was predicted by IGF-I levels reached at six months of SD-Lanreotide treatment (p = 0.04) and six months of HF-Lanreotide treatment (p = 0.01)., Conclusion: Our results demonstrated that initial IGF-I levels during SD-Lanreotide predicted the biochemical outcome after 12 months of HF-Lanreotide. Patients in whom HF-Lanreotide did not normalize IGF-I after 6 months of treatment remained uncontrolled 12 months after starting this regimen., Competing Interests: Declarations. Institutional review board statement: All procedures performed in the study were in accordance with the ethical standards of the institutional review board and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by the Institutional Review Board of the University Hospital “Fondazione Policlinico Universitario A. Gemelli IRCCS” in Rome, Italy (Protocol ID: 5132). Informed consent: Informed consent was obtained from all subjects involved in the study. Competing interests: All the authors declare no conflict of interest that could be perceived as prejudicing the impartiality of this paper. Sabrina Chiloiro recipient of Research grant to Institution from Ipsen, Pfizer, and Recordati. Andrea Giustina consultant for Amolyt, Ipsen, Pfizer, and Recordati and is Editor of Pituitary., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Objectives: The temporoparietal fascia flap (TPFF) has recently emerged as an option for skull base reconstruction in endoscopic transnasal surgery when vascularized nasal flaps are not available. This study provides a systematic literature review of its use in skull base surgery and describes a novel cohort of patients. Methods: PRISMA guidelines were used for the review. Patients undergoing skull base reconstruction with TPFF in our center from May 2022 to April 2024 were retrospectively included. Data were collected on pre- and post-operative clinical and radiological features, histology, surgical procedures, and complications. Results: Sixteen articles were selected, comprising 42 patients who underwent TPFF reconstruction for treatment of complex skull base pathologies. In total, 5 of 358 patients (0.9%) who underwent tumor resection via endoscopic transanal surgery in the study period in our institution required TPFF. All had been previously treated with surgery and radiation therapy for different pathologies (three chordomas, one giant pituitary neuroendocrine tumor (PitNET), and one sarcoma). Post-operative complications included CSF leak, which resolved after flap revision, and an internal carotid artery pseudoaneurysm requiring endovascular embolization. Conclusions: TPFF is an effective option for skull base reconstruction in complex cases and should be part of the armamentarium of the skull base surgeon.

Secondary adrenal insufficiency (SAI) is an endocrine disorder due to impaired secretion of ACTH resulting from any disease affecting the pituitary gland. Glucocorticoid replacement therapy is mandatory to ensure patient survival, haemodynamic stability, and quality of life. In fact, a correct dose adjustement is mandatory due to the fact that inappropriately low doses expose patients to hypoadrenal crisis, while inappropriately high doses contribute to glucose metabolic and cardiovascular deterioration. This review analyses the current evidence from available publications on the epidemiology and aetiology of SAI and examines the association between glucocorticoid replacement therapy and glucometabolic and cardiovascular effects., (© 2024. The Author(s).)

Background: Subcortical brain mapping in awake glioma surgery might optimize the extent of resection while minimizing neurological morbidity, but it requires a correct interpretation of responses evoked during surgery. To define, with a systematic review: 1) a comprehensive 'map' of the principal white matter bundles involved in awake surgery on language-related networks, describing the most employed tests and the expected responses; 2) In linguistics, a false friend is a word in a different language that looks or sounds like a word in given language but differs significantly in meaning. Similarly, our aim is to give the surgeons a comprehensive review of potentially misleading responses, namely "false friends", in subcortical language mapping., Methods: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Standardized data extraction was conducted., Results: Out of a total of 224 initial papers, 67 were included for analysis. Expected responses, common tests, and potential "false friends" were recorded for each of the following white matter bundles: frontal aslant tract, superior and inferior longitudinal fascicles, arcuate fascicle, inferior fronto-occipital fascicle, uncinate fascicle. Practical examples are discussed to underline the risk of intraoperative fallouts ("false friends") that might lead to an early interruption (false positive) or a risky surgical removal (false negative)., Conclusions: This paper represents a critical review of the present status of subcortical awake mapping and underlines practical "false-friend" in mapping critical crossroads in language-related networks., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: The potential advantages of exoscopy have been discussed theoretically for a long time. Such a concept holds significance, especially in the specific setting of the posterior cranial fossa (PCF), characterized by complex anatomy and long and narrow surgical corridors with relatively extreme working angles. We aimed to: 1) analyze the institutional preliminary case-based data on the use of the Robotic 3D Exoscope AEOS Aesculap in three different PCF approaches: retrosigmoid (RSA), midline suboccipital (MSA), and supracerebellar infratentorial via feedbacks was collected using a 20-point questionnaire, and 2) perform a comprehensive review of the literature concerning the use of EX in PCF surgery., Results: A total of 38 patients with neurosurgical pathologies underwent a neurosurgical procedure using the EX (Robotic 3D exoscope AEOS Aesculap) at our institution between January and March 2022. 21 surgeons were involved in the abovementioned PCF surgeries and answered the questionnaire. The main perceived advantages were in terms of ergonomics (67%), magnification (52%), and visualization of extreme angles. The main reported disadvantage was color vision (16, 76%), followed by manual mobility (24%). Concerning the review, the search of the literature yielded a total of 177 results. Upon full-text review, 17 articles were included, including 153 patients., Conclusions: In conclusion, our study provides a comprehensive evaluation of the advantages and challenges associated with using the exoscope in posterior fossa surgery, setting a precedent as the first to report on a questionnaire-based analysis of exoscope utilization in this specific domain., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Skeletal fragility is characterized by increased frequency of vertebral fractures (VFs) in acromegaly. Several trials were conducted to identify modifiable risk factors and predictors of VFs, with limited data on the prognostic role of GH receptor (GHR) isoforms. In this study, we investigated the potential role of GHR polymorphism on the occurrence of incidental VFs (i-VFs), in patients treated with second-line medical therapies., Methods: A longitudinal, retrospective, observational study was conducted on a cohort of 45 acromegalic patients not-responsive to first-generation somatostatin receptor ligands (fg-SRLs) and treated with GHR antagonist (Pegvisomant) or with the second-generation SRLs (Pasireotide long-acting release)., Results: Second line treatments were Pegvisomant plus fg-SRLs in 26 patients and Pasireotide LAR in 19 patients. From the group treated with fg-SRLs+Peg-V, the fl-GHR isoform was identified in 18 patients (69.2%) and the d3-GHR isoform in 8 patients (30.8%). I-VFs arose exclusively in fl-GHR isoform carriers (p=0.039). From the group treated with Pasireotide LAR, the fl-GHR isoform was identified in 11 patients (57.9%), and the d3-GHR isoform in 8 patients (42.1%). I-VFs arose exclusively in d3-GHR isoform carriers (p=0.018). Patients with fl-GHR isoform had a higher risk for i-VFs if treated with fg-SRL+Peg-V (OR: 1.6 95%IC: 1.1-2.3, p=0.04), and a lower risk if treated with Pasi-LAR (OR: 0.26 IC95%: 0.11-0.66, p=0.038)., Conclusions: Our data support a predictive role of the GHR isoforms for the occurrence of i-VFs in acromegalic patients treated with second-line drugs, tailored to the individual patient. The knowledge of the GHR polymorphism may facilitate the choice of second-line therapies, improving the therapeutic approach, in the context of personalized medicine., Competing Interests: SC, AB, AG, LDM have served as investigator for clinical trials funded by Novartis, Pfizer, Ipsen and Crinetics. SC and AB received grants from Pfizer. SC won the 2022 Arrigo Recordati Research Grant. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chiloiro, Costanza, Giampietro, Infante, Mattogno, Angelini, Gullì, Lauretti, Rigante, Olivi, De Marinis, Doglietto, Bianchi and Pontecorvi.)

Transbasal meningiomas1 are a rare group of tumors that grow intracranially, invade the skull base, and propagate extracranially; they are usually located at the level of the olfactory cribra and sphenoid wing.1-4 Transbasal tuberculum sellae meningiomas are a subset of these tumors, which extend into the suprasellar and sphenoid regions. The traditional transcranial approach for some transbasal meningiomas has recently evolved toward the transnasal endoscopic approach, which allows the removal of both the intranasal and intracranial components, reducing the manipulation of the optic nerves and neurovascular structures. Nevertheless, specific anatomical criteria must be present; the knowledge of specific anatomy5,6 and the surgeon's experience are fundamental for reaching the most favorable outcome.7-11 In this video, we present the case of a 50-year-old woman with a history of progressive visual impairment and scotoma in the left inferotemporal quadrant. Radiological examinations suggested a transbasal tuberculum meningioma that extended into the suprasellar region, sphenoid sinus, and optic canals. An endoscopic transtuberculum approach with intraoperative visual-evoked potentials12 was performed, allowing an early devascularization with the preservation of the superior hypophyseal arteries and the removal of the component extending in the medial portion of both optic canals. The postoperative MRI documented a gross total resection without complications. The patient reported an immediate improvement of the visual symptoms. Histopathology documented a meningioma (CNS World Health Organization grade 1) with bone invasion. The patient consented to the procedure and to the publication of her image; Institutional Review Board approval was not required for this single case report., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Background: The balance between comprehensive intraoperative neurophysiological monitoring (IONM) for both upper and lower limbs while ensuring the reliability of motor evoked potentials (MEPs) is paramount in motor area surgery. It is commonly difficult to obtain good simultaneous stimulation of both upper and lower limbs. A series of factors can bias MEP accuracy, and inappropriate stimulation intensity can result in unreliable monitoring. The presented IONM technique is based on the concurrent use of both transcranial and cortical strip electrodes to facilitate simultaneous monitoring of both upper and lower limbs at optimized stimulation intensities to increase IONM accuracy during motor area surgery., Methods: Ten nonconsecutive motor area tumors were studied. Good visualization of both limbs was observed in the series at a low amperage (1.2 mA from the strip electrode and 165.3 mA from the transcranial electrode)., Results: Our analysis confirms concordance between the IONM data and postoperative outcomes. An MEP reduction >20% and >50% correlated with postoperative modified Rankin scale score changes without false-negative IONM findings., Conclusions: The technique was demonstrated to be accurate in providing a good simultaneous neurophysiological evaluation of both upper and lower limbs with an optimized and stimulation amplitude. The technique results in a low encumbrance of electrodes in the surgical field. Our results have confirmed the "proof of concept," its reliability and feasibility., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background : The treatment of spheno-orbital meningiomas (SOMs) requires extensive bone resections, creating significant defects in a complex geometrical space. Bone reconstruction represents a fundamental step that optimizes long-term aesthetic and functional outcomes. In recent years, 3D printing technology has also been exploited for complex skull base reconstructions, but reports remain scarce. Methods : We retrospectively analyzed four consecutive patients who underwent SOM resection and one-step 3D PEEK customized reconstruction from 2019 to 2023. A systematic review of 3D printing customized implants for SOM was then performed. Results : All patients underwent a frontotemporal craniotomy, removal of SOM, and reconstruction of the superolateral orbital wall and pterional region. The aesthetic outcome was extremely satisfactory in all cases. No orbital implant malposition or infectious complications were documented. Eleven papers were included in the literature review, describing 27 patients. Most (23) patients underwent a single-stage reconstruction; in three cases, the implant was positioned to correct postoperative delayed enophthalmos. Porous titanium was the most used material (16 patients), while PEEK was used in three cases. Prosthesis malposition was described in two (7.4%) patients. Conclusions : Single-step reconstruction with a personalized 3D PEEK prosthesis represents a valid reconstruction technique for the treatment of SOMs with good aesthetic outcomes.

Given that glioma cells tend to infiltrate and migrate along WM tracts, leading to demyelination and axonal injuries, Diffusion Tensor Imaging (DTI) emerged as a promising tool for identifying major "high-risk areas" of recurrence within the peritumoral brain zone (PBZ) or at a distance throughout the adjacents white matter tracts. Of our systematic review is to answer the following research question: In patients with brain tumor, is DTI able to recognizes within the peri-tumoral brain zone (PBZ) areas more prone to local (near the surgical cavity) or remote recurrence compared to the conventional imaging techniques?. We conducted a comprehensive literature search to identify relevant studies in line with the PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols) guidelines. 15 papers were deemed compatible with our research question and included. To enhance the paper's readability, we have categorized our findings into two distinct groups: the first delves into the role of DTI in detecting PBZ sub-regions of infiltration and local recurrences (n = 8), while the second group explores the feasibility of DTI in detecting white matter tract infiltration and remote recurrences (n = 7). DTI values and, within a broader framework, radiomics investigations can provide precise, voxel-by-voxel insights into the state of PBZ and recurrences. Better defining the regions at risk for potential recurrence within the PBZ and along WM bundles will allow targeted therapy., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Context: The prompt control of acromegaly is a primary treatment aim for reducing related disease morbidity and mortality. First-generation somatostatin receptor ligands (fg-SRLs) are the cornerstone of medical therapies. A non-negligible number of patients do not respond to this treatment. Several predictors of fg-SRL response were identified, but a comprehensive prognostic model is lacking., Objective: We aimed to design a prognostic model based on clinical and biochemical parameters, and pathological features, including data on immune tumor microenvironment., Methods: A retrospective, monocenter, cohort study was performed on 67 medically naïve patients with acromegaly. Fifteen clinical, pathological, and radiological features were collected and analyzed as independent risk factors of fg-SRLs response, using univariable and multivariable logistic regression analyses. A stepwise selection method was applied to identify the final regression model. A nomogram was then obtained., Results: Thirty-seven patients were fg-SRLs responders. An increased risk to poor response to fg-SRLs were observed in somatotropinomas with absent/cytoplasmatic SSTR2 expression (OR 5.493 95% CI 1.19-25.16, P = .028), with low CD68+/CD8+ ratio (OR 1.162, 95% CI 1.01-1.33, P = .032). Radical surgical resection was associated with a low risk of poor fg-SRLs response (OR 0.106, 95% CI 0.025-0.447 P = .002). The nomogram obtained from the stepwise regression model was based on the CD68+/CD8+ ratio, SSTR2 score, and the persistence of postsurgery residual tumor and was able to predict the response to fg-SRLs with good accuracy (area under the curve 0.85)., Conclusion: Although our predictive model should be validated in prospective studies, our data suggest that this nomogram may represent an easy to use tool for predicting the fg-SRL outcome early., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: We aim to assess the role of a multidisciplinary approach in pituitary adenomas (PitNETs) classification, evaluate criteria concordance, and compare intraoperative assessments with post-operative MRIs for tumor remnants., Methods: Clinical, radiological, histological, and intra- and post-operative data of the treated PitNETs were extracted from prospectively created records. PitNETs were graded according to Trouillas, and the evaluation of the tumor remnants was recorded., Results: Of 362 PitNETs, 306 underwent surgery, with Trouillas grading assigned to 296. Eight-nine radiologically non-invasive PitNETs progressed to grades 1b (27), 2a (42), or 2b (20) due to proliferative or surgical invasiveness criteria. Twenty-six radiologically invasive tumors were graded 2b due to proliferative criteria. Surgical resection details and post-surgical MRI findings revealed that residual tumors were more common in grades 2a and 2b. During surgery, small tumor remnants were documented in 14 patients which were not visible on post-surgical MRI. Post-surgical MRIs identified remnants in 19 PitNETs not seen during surgery, located in lateral recesses of the sella (4), retrosellar (2), or suprasellar regions (7), along the medial wall of the cavernous sinus (6)., Conclusions: The Pituitary Board allows for the correct grading of PitNETs to be obtained and an accurate identification of high-risk patients who should undergo closer surveillance due to tumor remnants.

Objective: To evaluate disease characteristics and survival according to BRCA status, administration of poly-(ADP-ribose) polymerase inhibitors (PARPi), and surgery in patients with ovarian cancer and brain metastases., Methods: This is a monocentric retrospective cohort of patients with ovarian cancer and brain metastases treated between 2000 and 2021. Data were collected by a retrospective review of medical records and analyzed according to: (1) BRCA mutation; (2) PARPi before and after brain metastases; (3) surgery for brain metastases., Results: Eighty-five patients with ovarian cancer and brain metastasis and known BRCA status (31 BRCA mutated ( BRCA m), 54 BRCA wild-type ( BRCA wt)) were analyzed. Twenty-two patients had received PARPi before brain metastases diagnosis (11 BRCA m, 11 BRCA wt) and 12 after (8 BRCA m, 4 BRCA wt). Brain metastases occurred >1 year later in patients who had received previous PARPi. Survival was longer in the BRCA m group (median post-brain metastasis survival: BRCA m 23 months vs BRCA wt 8 months, p=0.0015). No differences were found based on BRCA status analyzing the population who did not receive PARPi after brain metastasis (median post-brain metastasis survival: BRCA m 8 months vs BRCA wt 8 months, p=0.31). In the BRCA m group, survival was worse in patients who had received previous PARPi (median post-brain metastasis survival: PARPi before, 7 months vs no-PARPi before, 24 months, p=0.003). If PARPi was administered after brain metastases, survival of the overall population improved (median post-brain metastasis survival: PARPi after, 46 months vs no-PARPi after, 8 months, p=0.00038).In cases of surgery for brain metastases, the prognosis seemed better (median post-brain metastasis survival: surgery 13 months vs no-surgery 8 months, p=0.036). Three variables were significantly associated with prolonged survival at multivariate analysis: BRCA mutation, multimodal treatment, and ≤1 previous chemotherapy line., Conclusions: BRCA mutations might impact brain metastasis occurrence and lead to better outcomes. In a multimodal treatment, surgery seems to affect survival even in cases of extracranial disease. PARPi use should be considered as it seems to prolong survival if administered after brain metastasis., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To refine a reliable and reproducible intraoperative visual evoked potentials (iVEPs) monitoring protocol during endoscopic transsphenoidal surgery. To assess the reliability of baseline iVEPs in predicting preoperative visual status and perioperative iVEP variation in predicting postoperative visual outcome., Methods: Sixty-four patients harboring tumors of the pituitary region were included. All patients underwent endoscopic endonasal approach (EEA) with iVEPs monitoring, using a totally intravenous anesthetic protocol. Ophthalmological evaluation included visual acuity and visual field studies., Results: Preoperatively, visual acuity was reduced in 86% and visual field in 76.5% of cases. Baseline iVEPs amplitude was significantly correlated with preoperative visual acuity and visual field (p = 0.001 and p = 0.0004, respectively), confirming the reliability of the neurophysiological/anesthetic protocol implemented. Importantly, perioperatively the variation in iVEPs amplitude was significantly correlated with the changes in visual acuity (p < 0.0001) and visual field (p = 0.0013). ROC analysis confirmed that iVEPs are an accurate predictor of perioperiative visual acuity improvement, with a 100% positive predictive value in patients with preoperative vision loss., Conclusions: iVEPs during EEA is highly reliable in describing preoperative visual function and can accurately predict postoperative vision improvement., Significance: iVEPs represent a promising resource for carrying out a more effective and safe endoscopic transsphenoidal surgery., (© 2023. The Author(s).)

Recently, advances in molecular biology and bioinformatics have allowed a more thorough understanding of tumorigenesis in aggressive PitNETs (pituitary neuroendocrine tumors) through the identification of specific essential genes, crucial molecular pathways, regulators, and effects of the tumoral microenvironment. Target therapies have been developed to cure oncology patients refractory to traditional treatments, introducing the concept of precision medicine. Preliminary data on PitNETs are derived from preclinical studies conducted on cell cultures, animal models, and a few case reports or small case series. This study comprehensively reviews the principal pathways involved in aggressive PitNETs, describing the potential target therapies. A search was conducted on Pubmed, Scopus, and Web of Science for English papers published between 1 January 2004, and 15 June 2023. 254 were selected, and the topics related to aggressive PitNETs were recorded and discussed in detail: epigenetic aspects, membrane proteins and receptors, metalloprotease, molecular pathways, PPRK, and the immune microenvironment. A comprehensive comprehension of the molecular mechanisms linked to PitNETs' aggressiveness and invasiveness is crucial. Despite promising preliminary findings, additional research and clinical trials are necessary to confirm the indications and effectiveness of target therapies for PitNETs.

Clival chordomas are rare but aggressive skull base tumors that pose significant treatment challenges and portend dismal prognosis. The aim of this study was to highlight the advantages and limitations of available treatments, to furnish prognostic indicators, and to shed light on novel therapeutic strategies. We conducted a retrospective study of clival chordomas that were surgically treated at our institution from 2003 to 2022; for comparison purposes, we provided a systematic review of published surgical series and, finally, we reviewed the most recent advancements in molecular research. A total of 42 patients underwent 85 surgeries; median follow-up was 15.8 years, overall survival rate was 49.9% at 10 years; meanwhile, progression-free survival was 26.6% at 10 years. A significantly improved survival was observed in younger patients (<50 years), in tumors with Ki67 ≤ 5% and when adjuvant radiotherapy was performed. To conclude, clival chordomas are aggressive tumors in which surgery and radiotherapy play a fundamental role while molecular targeted drugs still have an ancillary position. Recognizing risk factors for recurrence and performing a molecular characterization of more aggressive lesions may be the key to future effective treatment.

Background: The anatomy laboratory can provide the ideal setting for the preclinical phase of neurosurgical research. Our purpose is to comprehensively and critically review the preclinical anatomical quantification methods used in cranial neurosurgery., Methods: A systematic review was conducted following the PRISMA guidelines. The PubMed, Ovid MEDLINE, and Ovid EMBASE databases were searched, yielding 1667 papers. A statistical analysis was performed using R., Results: The included studies were published from 1996 to 2023. The risk of bias assessment indicated high-quality studies. Target exposure was the most studied feature (81.7%), mainly with area quantification (64.9%). The surgical corridor was quantified in 60.9% of studies, more commonly with the quantification of the angle of view (60%). Neuronavigation-based methods benefit from quantifying the surgical pyramid features that define a cranial neurosurgical approach and allowing post-dissection data analyses. Direct measurements might diminish the error that is inherent to navigation methods and are useful to collect a small amount of data., Conclusion: Quantifying neurosurgical approaches in the anatomy laboratory provides an objective assessment of the surgical corridor and target exposure. There is currently limited comparability among quantitative neurosurgical anatomy studies; sharing common research methods will provide comparable data that might also be investigated with artificial intelligence methods.

Purpose: the aim of this multicenter study is to preliminarily assess the role of the Endoscopic Endonasal Approach (EEA) in ultra-early (i.e., within 12 h) management of selected neurosurgical emergencies in terms of clinical and radiological outcomes., Methods: 26 patients affected by sellar/parasellar pathologies with rapid progression of symptoms were managed with EEA within 12 h from diagnosis in three Italian tertiary referral Centers from January 2016 to December 2019. Both clinical and radiological data have been collected preoperatively as well as post-operatively in order to perform retrospective analysis., Results: The average time from admission to the operating room was 5.5 h (±2.3). The extent of resection was gross-total in 20 (76.9%), subtotal in 6 (23.1%) patients. One patient experienced re-bleeding after a subtotal removal of a hemorrhagic lesion. Patients with a longer time from admission (>4 h) to the operatory room (OR) experienced stable impairment of the visual acuity ( p = 0.033) and visual field ( p = 0.029) in the post-operative setting., Conclusions: The Endoscopic Endonasal Approach represents a safe, effective technique that can be efficiently used with good results in the management of selected neurosurgical emergencies in centers with adequate experience.

Peripheral nerve sheath tumors (PNST) of the retroperitoneum are rare and are often treated by general surgeons dealing with retroperitoneal cancers. However, resection without the correct microsurgical technique can cause permanent neurological deficits and pain. Here, we discuss our interdisciplinary approach based on the integration of expertise from neurosurgery and abdominal surgery, allowing for both safe exposure and nerve-sparing microsurgical resection of these lesions. We present a series of 15 patients who underwent resection of benign retroperitoneal or pelvic PNST at our institution. The mean age of patients was 48.4 years; 67% were female. Tumors were 14 schwannomas and 1 neurofibroma. Eight patients (53%) reported neurologic symptoms preoperatively. The rate of complete resection was 87% (n = 13); all symptomatic patients showed improvement of their preoperative symptoms. There were no postoperative motor deficits; one patient (7%) developed a permanent sensory deficit. At a mean postoperative follow-up of 31 months, we observed no recurrences. To our best knowledge, this is the second-largest series of benign retroperitoneal PNST consistently managed with microsurgical techniques. Our experience confirms that interdisciplinary management allows for safe treatment of these tumors with good neurological and oncological outcomes.

Pituitary metastases are rare. Until now, few cases have been reported; about 50% of pituitary metastases originate from breast or lung cancers. We describe the clinical case of a primary colon carcinoma first presenting with a pituitary metastasis. A 76-year-old woman, with no history of malignancy, presented with headache, dizziness, and diplopia, at the Emergency Department. The neurologic examination was remarkable for complete left ophthalmoplegia with sensitivity deficit on the left side of the face. Radiologic investigations documented a voluminous sellar and suprasellar lesion, with extension in the left cavernous sinus and temporal lobe. Pituitary hormone levels were suggestive of anterior hypopituitarism and mild hyperprolactinemia. Subtotal surgical removal of the lesion was achieved through a trans-sphenoidal endoscopic endonasal approach. The histological examination disclosed a metastasis of gastrointestinal adenocarcinoma. A subsequent colonoscopy identified right colon cancer. A contrasted total-body computerized tomography ruled out other metastases. Postsurgical MRI showed a stable parasellar residual tumor. Conventional radiotherapy was scheduled. This case underlines the importance of considering pituitary metastases in the differential diagnosis of aggressive pituitary lesions, which should be managed in a pituitary tumor center of excellence through a multidisciplinary approach, for the complexity in diagnosis and therapeutic management of this rare condition., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Somatotropinomas are pituitary tumors with a heterogenous clinical behavior. The tumor microenvironment regulates the interaction between tumor cells and the host immune system, potentially modulating tumor behavior. Here, we aimed to investigate the tumor immune infiltration in a cohort of medically naïve acromegaly patients. A retrospective, monocenter study was designed to analyze the presence of CD3+, CD20+, CD138+, CD4+, CD8+, CD68+ immune cells in samples of somatotropinomas and their prognostic significance on tumor behavior and response to first generation somatostatin analogs (fg-SSA). Thirty-six patients (23 females) were included in the study. Macroadenomas were identified in 23 cases: 12 with cavernous sinus invasion. The number of CD8+ lymphocytes positively correlated with CD4+ lymphocytes (p = .05, r:0.245) and with CD68+ macrophages (p = .01, r = 0.291). The CD8+/CD4+ ratio inversely correlated with CD68+/CD8+ ratio (p < .001, r = -0.626). CD68+ macrophages positively correlated with tumor size (maximum diameter p = .003, r = 0.574; volume p = .009, r = 0.566) and were more numerous in somatotropinomas with Ki-67 > 3% (median 65/HPF, IQR:15), compared to cases with Ki67 < 3% (median 50/HPF, IQR:22, p < .001). CD8+ and CD138+ lymphocytes were more numerous in cases responsive to fg-SSA (respectively median 18/HPF IQR:18 and median 8/HPF IQR: 6.5) as compared to fg-SSA nonresponsive cases (median 14.5/HPF IQR:40 p = .03; median 3.5/HPF IQR: 14 p = .03). CD8+ lymphocytes act as single predictor of response to fg-SSA, independently from age, GH and IGF-I levels, tumor dimension and invasion. Our results support that lymphocytes and macrophages generate an immune network in somatotropinomas and the characteristic of the immune infiltrate may predict treatment outcome., (© 2023 British Society for Neuroendocrinology.)

Aim: To present the ability of standard intraoperative neuronavigation to reliably identify the stylomastoid foramen, thus providing a quick and effective recognition of the facial nerve at its exit from the skull base., Material and Methods: We describe the technical nuances of this procedure by presenting two surgical cases who underwent hypoglossal-facial nerve anastomosis for complete facial nerve palsy occurring post removal of a giant vestibular schwannoma 6 months earlier., Results: CT-based neuronavigation allowed a quick and reliable identification of the stylomastoid foramen and of the facial nerve at its exit from the skull. The entire procedure lasted for 3 hours. Three months after the anastomosis, the first signs of facial muscle reinnervation were visible., Conclusion: The use of neuronavigation during hypoglossal-facial nerve anastomosis is a simple and cost-effective strategy to decrease operative duration and increase surgical effectiveness.

Background: Intramedullary spinal cord tumors (IMSCTs) are rare neoplasms and their management involves tumors resection in most cases. Regarding the surgical procedure, adequate identification of tumor boundaries is paramount to achieve an extensive tumor resection. Fluorescence image-guided surgery (FIGS) has become an increasing popular intraoperative technique used in spine neuro-oncology surgery. However, evidence is lacking of their usefulness and their safety in spinal tumors. Therefore, the aim of the present study is to give an update of the existing literature and systematically review all studies that focus on the most-used fluorophores (5 aminolevulinic acid [5-ALA], sodium fluorescein, and indocyanine green [ICG]) in IMSCTs., Methods: Using PubMed and Scopus, we performed a systematic review in accordance with the PRISMA protocol and screened all original studies involving humans treated for neurosurgical conditions and studies evaluating FIGS application in IMSCTs., Results: After the screening phase, 27 articles were found to be relevant. The literature results were grouped according to the used fluorophores, resulting in 3 groups: 5-ALA (10 studies); fluorescein (5 studies), and ICG (12 studies)., Conclusions: In intramedullary tumor surgery, 5-ALA has shown its usefulness in identifying the tumor margins and in searching for residues because of its properties as a tumor-specific metabolic marker. Sodium fluorescein and ICG video angiography have shown promising application in ependymoma and hemangioblastomas surgery, respectively. However, the evolving role of fluorescent dyes in guiding surgical strategies in intramedullary spinal tumor has yet to be shown by randomized clinical trials., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Trans-sphenoidal endoscopic surgery has drawn huge benefits from advances in surgical visualization. The Ultra-HD "4K" endoscope has improved 4-fold image resolution compared with HD, but its actual advantages are unclear. Aim of the present study was to assess its usefulness in the early outcome of trans-sphenoidal surgery., Methods: We analyzed a series of 199 trans-sphenoidal pituitary adenoma procedures performed by an experienced team using alternatively HD (N.=102) or 4K (N.=97) endoscopes. We evaluated extent of resection both subjectively, based on intraoperative surgeon's impression, and objectively based on postoperative MR scan., Results: Baseline patients' characteristics were balanced. Objective near-total and total resection rates were comparable between 4K and HD groups (91.5% vs. 86.3% and 64.9% vs. 56.9%, respectively). 4K endoscope slightly improved resection rate in recurrent adenoma. At multivariate analysis, the only independent prognosticator of total resection was cavernous sinus invasion. Importantly, 4K endoscope enhanced the reliability of intraoperative judgement on extent of resection, significantly reducing unexpected residuals (12.8% vs. 33.3% for HD). Operative features and clinical outcomes were similar., Conclusions: The HD endoscope remains the standard-of-care for pituitary surgery. The 4K enhanced, "immersive" visualization significantly improved the reliability of surgeon's judgment on resection and might be useful in surgically difficult cases.

The onco-functional balance in neuro-oncology requires maximizing tumor removal while rigorously preserving patients' neurological status. When postoperative worsening prevents the implementation of oncologic treatments, palliative care service offers an individualized path for symptom and psychosocial distress relief. Here, we report on a series of 25 patients operated on for malignant brain tumor who did not undergo adjuvant treatments after neurosurgery; they represented 3.9% of the whole institutional surgical series. These patients were significantly older and had a lower preoperative Karnofsky performance status than the whole cohort. Importantly, in 22 out of 25 (88%) cases, a surgical complication occurred, leading to clinical worsening in 21 patients. For the end of life, the majority of patients chose a hospice care facility (72%). While a careful selection of brain tumor patients candidate to neurosurgery is required, palliative care service provided invaluable help in coping with patients' and caregivers' needs.

Background and aim : Ever since the discovery of tumor-associated immune cells, there has been growing interest in the understanding of the mechanisms underlying the crosstalk between these cells and tumor cells. A "seed and soil" approach has been recently introduced to describe the glioblastoma (GBM) landscape: tumor microenvironments act as fertile "soil" and interact with the "seed" (glial and stem cells compartment). In the following article, we provide a systematic review of the current evidence pertaining to the characterization of glioma-associated macrophages and microglia (GAMs) and microglia and macrophage cells in the glioma tumor microenvironment (TME). Methods: An online literature search was launched on PubMed Medline and Scopus using the following research string: "((Glioma associated macrophages OR GAM OR Microglia) AND (glioblastoma tumor microenvironment OR TME))". The last search for articles pertinent to the topic was conducted in February 2022. Results: The search of the literature yielded a total of 349 results. A total of 235 studies were found to be relevant to our research question and were assessed for eligibility. Upon a full-text review, 58 articles were included in the review. The reviewed papers were further divided into three categories based on their focus: (1) Microglia maintenance of immunological homeostasis and protection against autoimmunity; (2) Microglia crosstalk with dedifferentiated and stem-like glioblastoma cells; (3) Microglia migratory behavior and its activation pattern. Conclusions: Aggressive growth, inevitable recurrence, and scarce response to immunotherapies are driving the necessity to focus on the GBM TME from a different perspective to possibly disentangle its role as a fertile 'soil' for tumor progression and identify within it feasible therapeutic targets. Against this background, our systematic review confirmed microglia to play a paramount role in promoting GBM progression and relapse after treatments. The correct and extensive understanding of microglia-glioma crosstalk could help in understanding the physiopathology of this complex disease, possibly opening scenarios for improvement of treatments.

Endoscopic transsphenoidal surgery is a surgical technique introduced in the last 20 years for the treatment of skull base pathologies and, in particular, pituitary tumours. Although the prevalence of work-related musculoskeletal disorders is usually significantly higher in endoscopists and minimally invasive surgeons compared to other surgical and medical specialties, reviews on the prevalence of disorders among neurosurgeons dedicated to endoscopic transsphenoidal surgery are not available. This article performs a systematic review to identify the work-related musculoskeletal disorders among transsphenoidal neurosurgeons, their prevalence and the ergonomic interventions proposed to reduce risk factors and prevent disorders. The results show that the ergonomics of transsphenoidal neurosurgeons is an under-investigated topic. Indeed, specific prevalence data are not available. In addition, only a few papers suggest interventions and guidelines, but without objective assessment of the outcomes to confirm the ergonomic benefit. Based on these gaps in the literature, a future research agenda is proposed.

Purpose  Transsphenoidal surgery (TSS) for pituitary adenomas can be complicated by the occurrence of intraoperative cerebrospinal fluid (CSF) leakage (IOL). IOL significantly affects the course of surgery predisposing to the development of postoperative CSF leakage, a major source of morbidity and mortality in the postoperative period. The authors trained and internally validated the Random Forest (RF) prediction model to preoperatively identify patients at high risk for IOL. A locally interpretable model-agnostic explanations (LIME) algorithm is employed to elucidate the main drivers behind each machine learning (ML) model prediction. Methods  The data of 210 patients who underwent TSS were collected; first, risk factors for IOL were identified via conventional statistical methods (multivariable logistic regression). Then, the authors trained, optimized, and audited a RF prediction model. Results  IOL reported in 45 patients (21.5%). The recursive feature selection algorithm identified the following variables as the most significant determinants of IOL: Knosp's grade, sellar Hardy's grade, suprasellar Hardy's grade, tumor diameter (on X, Y, and Z axes), intercarotid distance, and secreting status (nonfunctioning and growth hormone [GH] secreting). Leveraging the predictive values of these variables, the RF prediction model achieved an area under the curve (AUC) of 0.83 (95% confidence interval [CI]: 0.78; 0.86), significantly outperforming the multivariable logistic regression model (AUC = 0.63). Conclusion  A RF model that reliably identifies patients at risk for IOL was successfully trained and internally validated. ML-based prediction models can predict events that were previously judged nearly unpredictable; their deployment in clinical practice may result in improved patient care and reduced postoperative morbidity and healthcare costs., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Background:  Different surgical approaches have been developed to manage lesions of the anterior and middle skull base areas. Frontal, pterional, bifrontal, and fronto-orbito-zygomatic approaches are traditionally used to reach these regions. With advancements in the neurosurgical field, skull opening should be simple and as minimally invasive as possible, tailored on the surgical corridor to the target. The supraorbital approach and the "keyhole" concept have been introduced and popularized by Axel Perneczky starting from 1998 and are now considered a part of everyday practice. The extended possibilities of this surgical route, considering the reachable targets and surgical limits, are described and systematically analyzed, including a description of the salient surgical anatomy, presenting different illustrative cases., Methods and Results:  Different illustrative cases are presented and discussed to underline the potentials and limits of the minimally invasive subfrontal approach (MISFA) and the possibilities to tailoring the craniotomy on the basis of the targets: extra-axial lesions with different localizations (anterior roof of the orbit, olfactory groove, tuberculum sellae, medial third of the sphenoid wing, anterior and posterior clinoid process), deeper intra-axial lesions (gyrus rectus, medial temporal lobe-uncus-amygdala-anterior hippocampus), and vascular lesions (anterior communicating aneurysm). Each case has been preoperatively planned considering the anatomical and radiologic features and using virtual simulation software to tailor the best possible corridor to reach the surgical target., Conclusions:  The MISFA is a safe multicorridor approach that can be used efficiently to manage lesions of the anterior and middle skull base areas with extremely low approach-related morbidity., Competing Interests: None declared., (Thieme. All rights reserved.)

Brain biopsy is the gold standard in order to establish the diagnosis of unresectable brain tumors. Few studies have investigated the long-term outcomes of biopsy patients. The aim of this single-institution-based study was to assess the concordance between radiological and histopathological diagnoses, and the long-term patient outcome. Ninety-three patients who underwent brain biopsy in the last 5 years were analyzed. We included patients treated with stereotactically guided needle, open, and neuroendoscopic biopsies. Most patients (86%) received needle biopsy. Gliomas and primary brain lymphomas comprised 88.2% of cases. The diagnostic yield was 95.7%. Serious complication and death rates were 3.2% and 2.1%, respectively. The concordance rate between radiological and histological diagnoses was 93%. Notably, the positive predictive value of radiological diagnosis of lymphoma was 100%. Biopsy allowed specific treatment in 72% of cases. Disease-related neurological worsening was the main reason that precluded adjuvant treatment. Adjuvant treatment, in turn, was the strongest prognostic factor, since the median overall survival was 11 months with vs. 2 months without treatment ( p = 0.0002). Finally, advanced molecular evaluations can be obtained on glioma biopsy specimens to provide integrated diagnoses and individually tailored treatments. We conclude that, despite the huge advances in imaging techniques, biopsy is required when an adjuvant treatment is recommended, particularly in gliomas.

Background:  Different types of skull base tumors and intracranial aneurysms may lead to compression of the optic pathways. Since most of them are biologically benign conditions, the first aim of surgery is preservation of optic nerves rather than the oncologic radicality., Materials and Methods:  Based on the progressive technical refinements coming from our institutional experience of optic nerve compression from aneurysms and extra-axial tumors, we analyzed the surgical steps to release nerves and chiasm during tumor debulking and aneurysm clipping., Results:  We distinguished vascular and tumor lesions according to the main direction of optic nerve compression: lateral to medial, medial to lateral, inferior to superior, and anterior to posterior. We also identified four fundamental sequential maneuvers to release the optic nerve, which are (1) falciform ligament (FL) section, (2) optic canal unroofing, (3) anterior clinoid process drilling, and (4) optic strut removal. The FL section is always recommended when a gentle manipulation of the optic nerve is required. Optic canal unroofing is suggested in case of lateral-to-medial compression (i.e., clinoid meningiomas), medial-to-lateral compression (i.e., tuberculum sellae meningiomas), and inferior-to-superior compression (i.e., suprasellar lesions). Anterior clinoidectomy and optic strut removal may be necessary in case of lateral-to-medial compression from paraclinoid aneurysms or meningiomas., Conclusions:  Preservation of the visual function is the main goal of surgery for tumors and aneurysms causing optic nerve compression. This mandatory principle guides the approach, the timing, and the technical strategy to release the optic nerve, and is principally based on the direction of the compression vector., Competing Interests: None declared., (Thieme. All rights reserved.)

Introduction: Primary autoimmune hypophysitis (PAHs) is a rare inflammatory disease of the pituitary gland. Although largely investigated, the pathogenesis of PAH is not completely clarified. We aimed to investigate the immune response in PAHs., Material and Methods: Serum anti-pituitary and anti-hypothalamus antibodies (respectively APAs and AHAs) were investigated though an indirect immunofluorescence on monkey hypophysis and hypothalamus slides, serum cytokines though an array membrane and cell-mediated immunity though the white blood cells count., Results: Nineteen PAH cases entered the study. APA or AHA were identified in all cases. APA were detected in 13 patients (68.4%) and AHA in 13 patients (68.4%). Ten patients (52.6%) were simultaneously positive for both APA and AHA. The prevalence of APAs and AHAs was higher as compared to those observed in 50 health controls (respectively 14% p < 0.001 and 24% p = 0.004) and in 100 not-secreting pituitary adenoma (NFPAs) (respectively 22% p = 0.002 and 8% p < 0.001). Similarly, the prevalence of simultaneous positivity for APA and AHA (52.9%) was higher as compared to the those detected in patients affected by NFPAs (0%; p < 0.001) and in health controls (16% p = 0.002). No differences were identified between PAHs and controls at qualitative and quantitative analysis of serum cytokines and white blood cells count., Conclusions: This study suggest that APA and AHA may be detected in an high percentage of PAH cases and that their simultaneous identification may be useful for the differential diagnosis between PAH and NFPAs, in an appropriate clinical context.

Introduction: Prolactin-secreting pituitary tumors (PRL-omas) are generally benign neoplasia. However, a percentage of cases show aggressive behavior. Prognostic markers may allow for the identification of aggressive cases. In this study, we investigated the prognostic role of galectin-3 and the estrogen receptor alpha (ERα), as predictive biomarkers of aggressiveness and poor prognosis., Patients and Methods: A mono-centric and retrospective study was conducted on consecutive cases of PRL-omas that underwent first line treatment with surgery and were followed-up for at least five years. The immunohistochemical expression of ERα and galectin-3 was investigated in each case., Results: 36 patients were enrolled. Galectin-3 resulted positive in 11 patients (30.6%). The median expression of ERα was 85% (IQR: 37). Among the group of 21 patients who underwent radical surgery (58.3%), recurrence occurred in 12 cases (33.3%). 27 patients were treated post-surgery with a dopamine agonist (DA) (12 for recurrence and 22 for a history of partial surgery). 13 patients (48.1%) were responsive to DA. Six of 11 cases positive for galactin-3 underwent partial surgery (54.5%, p<0.001). Recurrence occurred in all five cases that underwent radical surgery, which were also positive for galectin-3 (p=0.03). Galectin-3 resulted positive in 9 patients resistant to DA treatment (81.1%, p=0.01). ERα expression was lower in tumors positive for galectin-3 (p<0.001), with mitotic activity (p=0.012), with higher Ki67 Li (p<0.001), and in males with post-surgical recurrence (p<0.001)., Conclusion: Galectin-3 and ERα play as markers of aggressiveness and prognosis in PRL-omas and may be tested to identify the aggressive forms of the disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bima, Chiloiro, Giampietro, Gessi, Mattogno, Lauretti, Anile, Rindi, Pontecorvi, De Marinis and Bianchi.)

Background: Prolactinomas represent a unique challenge for endocrinologists and neurosurgeons. Considering recent innovations in surgical practice, the authors aimed to investigate the best management for prolactinomas., Methods: A retrospective, cross-sectional and monocentric study was designed. Consecutive patients affected by prolactinomas were enrolled if treated with a first-line treatment with a dopamine agonist (DA) or trans-sphenoidal surgery (TSS). Patients carried giant prolactinomas, and those with a follow-up <12 months were excluded., Results: Two hundred and fifty-nine patients were enrolled. The first treatment was DA for 140 patients and TS for 119 cases. One hundred and forty-six of 249 patients (58.6%) needed a second therapy. The mean follow-up was 102.2 months (12-438 months). Surgery highly impacted on the cure rate-in particular, in females ( p = 0.0021) and in microprolactinomas ( p = 0.0020). Considering the multivariate analysis, the female gender and surgical treatment in the course of the clinical history were the only independent positive predictors of a cure at the end of 5 years follow-up ( p = 0.0016, p = 0.0005). The evaluation of serum prolactin (24 hours after TSS) revealed that 86.4% of patients with postoperative prolactin (PRL) ≤10 ng/mL were cured at the end of the follow-up ( p < 0.0001)., Conclusions: According to our experience, surgery allows a high cure rate of prolactinomas, particularly in females with microadenoma, with a good safety profile. TSS for prolactinomas should be considered as a concrete option, during the multidisciplinary evaluation, in centers of reference for pituitary diseases.

Objective  Different surgical set-ups for endoscopic transsphenoidal surgery (ETS) have been described, but studies on their ergonomics are limited. The aim of this article is to describe present trends in the ergonomics of ETS. Design and Participants  A 33-question, web-based survey was sent to North American Skull Base Society members in 2018 and 116 responded to it (16% of all members). Most respondents were from North America (76%), in academic practice (87%), and neurosurgeons (65%); they had more than 5 years of experience in ETS (73%), had received specific training (66%), and performed at least 5 procedures/mo (55%). Results  Mean reported time for standard and complex procedures were 3.7 and 6.3 hours, respectively. The patient's body is usually positioned in a straight, supine position (84%); the head is in a neutral position (46%) or rotated to the side (38%). Most surgeons perform a binostril technique, work with a partner (95%), and operate standing (94%), holding suction (89%) and dissector (83%); sometimes the endoscope is held by the primary surgeon (22-24%). The second surgeon usually holds the endoscope (72%) and irrigation (42%). During tumor removal most surgeons stand on the same side (65-66%). Many respondents report strain at the dorsolumbar (50%) or cervical (26%) level. Almost one-third of surgeons incorporate a pause during surgery to stretch, and approximately half exercise to be fit for surgery; 16% had sought medical attention for ergonomic-related symptoms. Conclusion  Most respondents value ergonomics in ETS. The variability in surgical set-ups and the relatively high report of complaints underline the need for further studies to optimize ergonomics in ETS., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Background: The treatment of acromegaly resistant to first-generation somatostatin receptor ligands (SRLs) is often difficult. Pegvisomant and Pasireotide LAR are mostly used in these subset of patients, as second line therapies. Choice of the type of second line therapies is difficult, since predictors of response are still unclear, impairing personalized therapy. We aimed to investigate predictors of response to Pegvisomant and Pasireotide LAR., Methods: Seventy-four acromegaly patients entered this observational, cross-sectional and retrospective study if (i) resistant to high dose first-generation SRLs and (ii) treated with Pegvisomant and Pasireotide LAR for at least 12 consecutive months. Patients treated with radiotherapy in the previous 10 years were excluded., Results: Fourty-one patients were treated with Pegvisomant and 33 with Pasireotide LAR. At the end of the study, acromegaly was controlled in 35 patients treated with Pegvisomant (85.4%) and in 23 treated with Pasireotide LAR (69.7%). In this cohort, a poor Pegvisomant response and a shorter progression free time were observed in cases with tumor extension to the third ventricle (P = 0.004, HR: 1.6, 95%CI: 1.2-4.6), with a Ki67-Li >4% (P = 0.004, HR: 3.49, 95%CI: 1.4-4.0) and with pre-treatment IGF-I >3.3×ULN (P=0.03, HR: 1.3, 95%CI: 1.1-6.0). A poor Pasireotide LAR response and a shorter progression free time were observed in cases with tumor extension to the third ventricle (P=0.025, HR: 1.6 95%CI: 1.4-3.4), pre-treatment IGF-I >2.3×ULN (P=0.049, HR: 2.4, 95%CI: 1.4-8.0), absent/low SST5 membranous expression (P=0.023 HR: 4.56 95%CI: 1.3-6.4) and in patients carried the d3-delated GHR isoform (P=0.005, HR: 11.37, 95%CI: 1.3-20.0)., Conclusion: Molecular and clinical biomarkers can be useful in predicting the responsiveness to Pegvisomant and Pasireotide LAR.

Background: The introduction of recent innovations in the field of intraoperative imaging and neuronavigation, such as OArm Stealth Station, allows to obtain crucial intraoperative data by performing safer and controlled surgical procedures. As part of the improvement of surgical visual magnification and wide expansion of surgical corridors, the 3D-4K exoscope (EX) represents nowadays an interesting and useful tool. Transoral approach (TOA) represents the historical gold standard direct microsurgical route to ventral craniovertebral junction (CVJ)., Methods: We herein report a preliminary experience on 6 cases of 33 patients operated by TOA concerning the simultaneous application of OArm with Stealth Navigation system (Medtronic, Memphis, TN) and imaging system along with the 3D-4K EXs in TOA for the treatment of CVJ pathologies., Results: Neither intraoperative neurophysiological changes nor postoperative infections occurred, but a neurological improvement was evident in all the patients. A complete decompression along with stable instrumentation and fusion of the CVJ was accomplished in all cases at the maximum follow-up (mean: 16.8 months)., Conclusions: With EX, the role of surgeon become self-sufficient with a better individual surgical freedom compared to endoscopic surgery and excellent 3D vision and magnification. OArm allows an absolutely reliable intraoperative support for a more effective CVJ decompression. Nevertheless, with OArm-assisted neuronavigation, it can be difficult to navigate C1 lateral masses and C2 isthmi, and to convert 3D into 2D real-time navigation, it can become quite complicate. Finally, the association of EX and OArm appears more time consuming compared to the old fashion one., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Craniovertebral Junction and Spine.)