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Introduction  The endoscopic endonasal approach (EEA) might seem an "unnatural" route for intradural lesions such as meningiomas. The aim of this study is to critically revise our management of anterior skull base meningiomas to consider, in what cases it may be advantageous. Material and Methods  Each consecutive case of anterior skull base meningioma operated on through an EEA or combined endoscopic-transcranial approach at our institution, between 2003 and 2017, have been included. Tumors were classified on the basis of their location and intra or extracranial extension. Follow-up consisted of an MRI (magnetic resonance imaging) and a clinical examination 3 months after the surgery and then repeated annually. Results  Fifty-seven patients were included. The most common location was the tuberculum sellae (62%), followed by olfactory groove (14%), planum sphenoidale (12%), and frontal sinus (12%). Among these, 65% were intracranial, 7% were extracranial, and 28% both intra and extracranial. Radical removal was achieved in 44 cases (77%). Complications consisted in 10 CSF (cerebrospinal fluid) leaks (17.6%), 1 overpacking (1.7%), and 1 asymptomatic brain ischemia (1.7%). Visual acuity and campimetric deficits improved respectively in 67 and 76% of patients. Recurrence rate was of 14%. Conclusions  EEA presents many advantages in selected cases of anterior skull base meningioma. However, it is hampered by the relevant risk of CSF leak. We consider that it could be advantageous for planum/tuberculum sellae tumors. Conversely, for olfactory groove or frontal sinus meningiomas, it can be indicated for tumors with extracranial extension, while its role is still debatable for purely intracranial forms as considering our surgical results, it could be advantageous for midline planum/tuberculum sellae tumors. Conversely, it can be of first choice for olfactory groove or frontal sinus meningiomas with extracranial extension, while its role for purely intracranial forms is still debatable.

Background: Cavernous sinus (CS) invasion is one of the most unfavorable features of pituitary adenomas. The most widely used classification was proposed by Knosp in 1993 and revised in 2015. The aim of this study is to extend our previous experience by comparing the pre-operative neuroradiological assessment with the intra-operative endoscopic endonasal inspection in order to evaluate the real rate of CS invasion and analyze its correlation with the surgical outcome., Methods: Consecutive patients, who have undergone endoscopic endonasal surgery for a pituitary adenoma with Knosp grade greater than 1, have been included in this study. The intra-operative CS invasion was assesses basing on surgical reports. The surgical outcome has been evaluated with MRI, endocrinological, visual and neurological evaluation have been performed 3 months after surgery and then annually., Results: The series included 402 patients. Male-female ratio was 1:1 and median age was 56 years (range 15-85). We observed that 43% of cases with Knosp grade greater than 1 presented no CS invasion on surgical inspection. Knosp grade 4 was the only one corresponding in all cases to a real CS invasion. Radical tumor removal was achieved in 60%. while endocrinological remission was obtained in 37% of functioning adenomas. Better results were observed for lower Knosp grades., Conclusions: The endoscopic endonasal inspection is the most effective technique to detect CS invasion. Indeed, it can provide a direct visualization of the medial wall, permitting the assessment of its invasion and the management of those cases with diffuse involvement. We confirm that the revision to the Knosp classification has improved its prognostic role.

Background: The endoscopic endonasal opening of the optic canal has been recently proposed for tumors with medial invasion of this canal, such as tuberculum sellae meningiomas. Injury of the ophthalmic artery represents a dramatic risk during this maneuver. Therefore, the aim of this study was to analyze the endoscopic endonasal anatomy of the precanalicular and canalicular portion of this vessel, discussing its clinical implication., Methods: The course of the ophthalmic artery was analyzed through five endoscopic endonasal dissections, and 40 nonpathological consecutive MRAs were reviewed., Results: The ophthalmic artery arises from the intradural portion of the supraclinoid internal carotid artery, in 93 % of cases about 1.9 mm (range: 1-3) posterior to the falciform ligament. At the entrance into the optic canal, the ophthalmic artery is located infero-medially to the optic nerve in 13 % of cases. In 50 % of these cases the artery moves infero-laterally along its course, remaining in a medial position in the others. In cases with an non medial entrance of the ophthalmic artery, it runs infero-lateral to the optic nerve for its entire canalicular portion, with just one exception., Conclusion: The endoscopic endonasal approach gives a direct, extensive and panoramic view of the course of the precanalicular and canalicular portion of the ophthalmic artery. Dedicated high-field neuroimaging studies are of paramount importance in preoperative planning to evaluate the anatomy of the ophthalmic artery, reducing the risk of jeopardizing the vessel, particularly for those uncommon cases with an infero-medial course of the artery.

Background: Meningocele and meningoencephalocele of the lateral wall of the sphenoidal sinus (LWSS) are rare lesions, crossing the borders of multiple disciplines such as ear-nose-throat, maxillofacial, and neurologic surgery. We reviewed our surgical experience to analyze the role of the endoscopic endonasal approach and consider these pathologies from different perspectives., Methods: All consecutive cases of meningocele and meningoencephalocele of LWSS operated through an endoscopic endonasal approach from 1998 to 2015 in our institutions were collected. Medical history, focusing on previous episodes of cerebrospinal fluid leak, meningitis or seizures, was considered. The outcome was assessed considering the medical condition and the postoperative neuroimaging., Results: The series includes 23 patients (7 male, 16 female). Mean age was 52 years (26-73 years). Eleven cases were meningoencephaloceles and 12 meningoceles. A clear cerebrospinal fluid leak occurred on in 19 patients and was associated with meningitis in 3. Two were presenting a history of epilepsy. No complications were observed, but 1 case presented seizures on waking. At follow-up (mean 84 months, 4-167) each patient is in good clinical condition with no further episodes of leaking or seizures., Conclusions: Endoscopic endonasal surgery is a safe and effective approach for meningocele and meningoencephalocele of LWSS; it allows resection of herniated tissue and repair of the osteodural defect. The favorable clinical outcome and the possible effectiveness on seizures lead us to support this approach as first minimally invasive treatment also in presence of epilepsy, as a first low risk epilepsy surgical procedure., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To assess the role of high sensitivity next-generation sequencing (NGS) of CTNNB1 for the diagnosis of adamantinomatous craniopharyngiomas (aCPs) and of BRAF for that of papillary CPs (pCPs) in routinely processed surgical samples of non-adenomatous sellar lesions., Methods: Forty-five cases of patients operated for non-adenomatous masses of the sellar region between 2004 and 2014 were retrieved from the files of the Anatomic Pathology unit of the Bellaria Hospital in Bologna, Italy. BRAF and CTNNB1 mutation status was analyzed by NGS in samples smaller than 1 cm(3) and histological re-evaluation was performed on all cases., Results: CTNNB1 mutation analysis showed a sensitivity of 86.7 % and a specificity of 96.2 % for the diagnosis of aCPs. The specificity increased to 100 % considering that in one case, initially classified as a non-CP lesion (xanthogranuloma), the identification of a CTNNB1 S47R lead to histological re-evaluation and reclassification of the lesion as aCP. BRAF mutation analysis had a sensitivity of 76.9 % and a specificity of 96.4 % for the diagnosis of pCPs. The specificity increased to 100 % considering that in one case, initially classified as a Rathke cyst, the identification of BRAF V600E lead to histological re-evaluation and reclassification of the lesion as pCP., Conclusions: This study confirms the diagnostic relevance of the molecular alterations recently identified in aCPs and pCPs and shows how the identification of BRAF and CTNNB1 mutations can be instrumental for the proper classification of samples that contain limiting amounts of diagnostic lesional tissue.

Odontoidectomy is the treatment of choice for irreducible ventral cervical-medullary compression. The endonasal endoscopic approach is an innovative approach for odontoidectomy. The aim of this article is to identify in which conditions this approach is indicated, discussing variants of the technique for selected cases of craniovertebral malformation with platybasia. We believe that the technical difficulties of this approach are balanced by the advantages for patients. Some conditions related to the patient and to the anatomy of the craniovertebral junction may favor adoption of the endoscopic endonasal approach, which should be considered complementary and not alternative to standard approaches., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Among the fathers of transsphenoidal surgery, a relevant role should be reserved for Cesare Cavina (1888-1935). He had the merit to develop and popularize in Italy this approach for pituitary tumors, performing 47 transsphenoidal hypophysectomies out of his personal series of 66 patients between 1927 and 1935. He contributed to this surgery by introducing radiological control of the surgical trajectory to reduce the risk of complications and increase the safety of this approach. We think that both his short lifespan (he died when he was 47 years old) and the language of his papers (Italian and not English) are two important factors that have contributed to forgetting his role in the history of transsphenoidal surgery. We think that Prof. Cesare Cavina is definitively one of the fathers of transsphenoidal surgery and that it is important to preserve his memory.

Chordomas are rare, slow-growing neoplasms, characterized by locally aggressive growth patterns and high local recurrence rates. To the best of our knowledge, the MGMT promoter methylation status has not been studied in a population of patients with chordomas to determine if a biologic rationale exists to support the use of temozolomide. We here show for the first time that methylation of MGMT promoter is present in a significant portion or recurring clival chordomas; on the contrary in clival chordomas without recurrence MGMT promoter was always unmethylated (p = 0.0317). Although these observations need to be confirmed in a larger study population, our results (1) indicate that methylation of MGMT promoter is present in a significant portion of recurring chordomas, and (2) prompt further investigation into the potential role of temozolomide as an adjuvant treatment of these tumors.

Object In the last decade the indications for the endoscopic endonasal approach have been progressively expanded to include lesions that have not been traditionally considered amenable to resection through the transsphenoidal route. In this study, the authors analyze their experience with hypothalamic gliomas treated via the endoscopic endonasal approach. Methods Consecutive cases of hypothalamic gliomas treated since 2007 via an endoscopic endonasal approach were reviewed. Preoperative and postoperative neuroimaging as well as endocrinological, neurological, and visual symptoms were analyzed to assess the surgical outcome. Signs and symptoms of hypothalamic dysfunction including body mass index (BMI), memory, sleep-wake rhythm, and polyphagia were prospectively collected pre- and postoperatively to assess hypothalamic function. Quality of life was evaluated using the Katz scale. Results In the initial phase the endoscopic endonasal approach was adopted in 3 cases with a palliative intent, to obtain a biopsy sample or for debulking of the mass followed by radio- or chemotherapy. In 2 later cases it was successfully adopted to achieve gross-total tumor resection. Complications consisted of 2 postoperative CSF leaks, which required an endoscopic endonasal reintervention. Visual deficit improved in 3 cases and normalized in the other 2. Four patients developed diabetes insipidus, and 3 an anterior panhypopituitarism. All patients had a moderate increase in BMI. No patients presented with any other signs of hypothalamic damage, and their quality of life at follow-up is normal. Conclusions Despite the limitations of a short follow-up and small sample, the authors' early experience with the endoscopic endonasal approach has revealed it to be a direct, straightforward, and safe approach to third ventricle astrocytomas. It allowed the authors to perform tumor resection with the same microsurgical technique: dissecting the tumor with 2 hands, performing a central debulking, and controlling the bleeding with bipolar coagulation. The main limitations were represented by some anatomical conditions, such as the position of the chiasm and the anterior communicating artery complex and, finally, by the challenge of watertight plastic repair. To definitively evaluate the role of this approach in hypothalamic gliomas, a comparison with transcranial series would be necessary, but due to the rarity of these cases such a study is still lacking. The authors observed that more aggressive surgery is associated with a worse endocrinological outcome; thus they consider it to be an open question (in particular in prepubertal patients) whether radical removal is an advisable goal for hypothalamic gliomas.

The purpose of this retrospective study was to investigate the role of galectin-3 (LGALS3) expression in predicting the recurrence and the progression potential of prolactin (PRL) and adrenocorticotropic hormone (ACTH)-producing pituitary adenomas and its correlation with the RUNX1 and RUNX2 transcription factors involved in the regulation mechanism of LGALS3 expression. Clinical, neuroradiologic, and follow-up data from 92 pituitary adenomas, including 59 PRL cell adenomas and 33 ACTH-functioning pituitary adenomas, were collected. The LGALS3 expression was analyzed by both immunohistochemistry and quantitative real time-polymerase chain reaction, whereas RUNX1 and RUNX2 were analyzed by quantitative real time-polymerase chain reaction only. The data obtained indicated that invasive growth with suprasellar extension, Ki-67 labeling index, and LGALS3 immunohistochemical and/or LGALS3 messenger RNA levels are the most important histologic features for assessing a high risk of progression or recurrence of PRL- and ACTH-functioning pituitary adenomas. Multivariate Cox regression analysis assessed LGALS3 immunohistochemical positivity in at least 30% of neoplastic cells and/or LGALS3 messenger RNA positivity (P < .001) as strong predictive factors of recurrence/tumor progression followed by a Ki-67 labeling index greater than 3% (P = .019) in the 81 cases in which follow-up data were available. In addition, a significant correlation between LGALS3 and RUNX1 expression levels (P = .0435) was found. This retrospective immunohistochemical and molecular study demonstrated that LGALS3 expression appeared to be a predictive factor of the aggressive behavior of PRL- and ACTH-functioning pituitary adenomas, and its expression was correlated with RUNX1 expression levels., (© 2013.)

Objective: To evaluate the clinical and radiographic manifestations of pituitary metastases (PM), discuss the role of surgery, and briefly review the pertinent literature., Methods: At a single institution between January 1992 and July 2011, 15 patients with PM were surgically treated (all cases were confirmed by histologic analysis). Of patients, 14 complained of visual impairment, 8 complained of headache, 4 complained of ophthalmoplegia, and 11 complained of endocrine disturbances manifesting as diabetes insipidus (7 patients) and anterior hypopituitarism (4 patients)., Results: After transsphenoidal surgery, visual disturbances improved in 12 cases, headache improved in 5 cases, and ophthalmoplegia improved in 2 cases. Endocrinologic function remained unchanged in all cases. The mean survival time was 11.8 months (range, 3-43 months); one patient still survives after 33 months., Conclusions: The study cohort includes patients representing two clinical situations: (i) patients with a preoperative suspicion of PM and (ii) patients in whom the metastasis was an unexpected finding during surgery performed for a presumed pituitary adenoma. The former situation is indicative of the possibilities and limits of surgery, which may confirm the diagnosis but is only palliative, improving quality of life without improving life expectancy. The latter situation reveals how misleading clinical and radiographic features of PM can be. Considering these results, surgical treatment of PM should be specifically decided based on patient performance status, tumor staging, and patient preference., (Copyright © 2013 Elsevier Inc. All rights reserved.)

It is difficult to evaluate the recurrence and progression potential of pituitary adenomas at presentation. The World Health Organization classification of endocrine tumors suggests that invasion of the surrounding structures, size at presentation, an elevated mitotic index, a Ki-67 labeling index higher than 3%, and extensive p53 expression are indicators of aggressive behavior. Nevertheless, Ki-67 and p53 labeling index evaluation is subject to interobserver variability, and their cutoff values are controversial. In the present study, the prognostic value of Ki-67 and p53 protein labeling indices and their correlation with clinical and radiologic parameters were evaluated using digital image analysis in a series of 166 pituitary adenomas in patients having undergone a follow-up of at least 6 years to evaluate the impact on the recurrence and progression potential of pituitary adenomas. The data were analyzed using the receiver operating characteristic curve and classification and regression tree analysis. The results showed that, in the unstratified data set, the commonly used threshold of the Ki-67 index of 3% has a high specificity (89.5%) but a low sensitivity (53.8%). Unsatisfactory performance results were obtained by performing receiver operating characteristic curve analysis on the p53 labeling index. On the contrary, the classification and regression tree analysis-derived tree demonstrated that each pituitary adenoma subtype has specific prognostic factors. Specifically, the Ki-67 labeling index is a useful prognostic factor in nonfunctioning, adrenocorticotropin, and prolactin adenomas, but with different thresholds. In conclusion, our study emphasizes that the term pituitary adenomas includes different types of tumors, each one having specific prognostic factors., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: In the past 2 decades, various extracranial approaches to the cavernous sinus (CS), using either microscopic or endoscopic techniques, have been described. The aim of this study was to describe the distinctive anatomic features of these approaches and compare their efficacy in exposing the sella and parasellar areas., Methods: Ten adult cadaver heads with red latex injected in the arterial system were used. Five different approaches were performed: 1) endonasal microscopic transsphenoidal approach; 2) sublabial microscopic transsphenoidal approach, including its variation described by Fraioli et al. ; 3) transmaxillary microscopic approach; 4) paraseptal endoscopic transsphenoidal approach; and 5) transethmoid-pterygoid-sphenoidal endoscopic approach. The CS exposition was evaluated for each approach and a grading system, which considers surgical maneuverability as well as visualization, was used., Results: The medial CS compartment is well exposed with all endoscopic and microscopic transsphenoidal approaches, but it is insufficiently exposed with the transmaxillary approach. The variation to the sublabial microscopic approach suggested by Fraioli et al. allows its widest microsurgical exposure. The lateral compartment is well visualized with the transmaxillary microscopic and the endoscopic approaches. The major anatomic structures that can limit exposure of the CS lateral compartment are the posterior ethmoid and medial pterygoid process., Conclusion: The sublabial transsphenoidal microscopic approach, with its variations, allows the most versatile extracranial microscopic exposure of the sella and CS. The paraseptal, binostril endoscopic approach allows a very good exposure of the CS; the transethmoid-pterygoid-sphenoidal endoscopic approach achieves the best maneuverability in the lateral compartment of the CS.

Objective: Purely intradural clival chordomas are rare neoplasms, and only a few cases have been reported. The reported cases present features similar to ecchordosis physaliphora, which is a notochordal remnant. We describe these 2 entities and their differential diagnoses, clinical courses, and management. This is the first reported case to be treated using a neuroendoscopic technique., Clinical Presentation: A 60-year-old man presenting with memory loss underwent magnetic resonance imaging, which revealed an intradural retroclival mass without bone involvement., Intervention: The patient underwent an endoscopic transsphenoidal-transclival procedure with subtotal removal of the tumor. Histological findings confirmed the diagnosis of a chordoma., Conclusion: Even if some parameters exist for a differential diagnosis, ecchordosis physaliphora and intradural chordoma may represent different aspects of the spectrum of the same pathology. Intradural clival chordomas have a better prognosis with respect to classic chordomas. Therefore, in subtotal removal such as that performed in our case, postoperative radiation therapy should be performed only if a regrowth of the remnant is seen during neuroradiological follow-up.

Objective: The endoscope has recently been applied to the supradiaphragmatic transsphenoidal approach, but only case reports dealing with different pathological features have been described. The authors present their experience with this technique in 10 patients with craniopharyngiomas., Methods: A pure endoscopic endonasal technique was used. From November 1998 through May 2005, four males and six females with a craniopharyngioma, either purely supradiaphragmatic (six patients) or with a significant suprasellar component (four patients), were treated. The tumors had a mean diameter of 2.9 cm (range, 1-4 cm); four patients had a major prechiasmatic component and six had a retrochiasmatic one., Results: Seven total, one subtotal, and two partial resections were obtained. Vision symptoms improved significantly in six out of eight patients. Endocrine function did not improve after surgery, and diabetes insipidus was the most frequent deficit, although it was transient in five out of eight patients. Cerebrospinal fluid leak was the most frequent complication and required reoperation in two patients. Postoperative obesity occurred in two patients. No recurrence has yet been documented in the total resection group. The mean follow-up period is 37 months (range, 3-75 mo)., Conclusion: The endoscopic technique allows results comparable with the best microscopic series. We think that this technique increases the safety of the procedure because of improved vision. Further studies are required to better define the exact location of the tumor with respect to the arachnoidal plane, the extra-arachnoidal craniopharyngioma being the most suitable for a radical removal using a transsphenoidal supradiaphragmatic approach.

Objective: We report our experience with endoscopic transsphenoidal or extended endoscopic transsphenoidal approaches for the treatment of cranial base lesions such as clival chordomas and chondrosarcomas., Methods: Between May 1998 and April 2004, 11 patients (four were recurrences because they previously had been treated with surgery and/or radiotherapy) underwent transnasal transsphenoidal endoscopic surgery for cranial base chordomas and chondrosarcomas at the Neurosurgical Department of Bellaria Hospital in Bologna. The transsphenoidal endoscopic approach and the ethmoid-pterygo-sphenoidal endoscopic approach were used to accomplish resection of the lesions involving the clivus and extending up to the parasellar region and to the petrous apex, or within the cavernous sinus., Results: Patient follow-up periods ranged from 15 to 69 months (mean, 27 mo). Three patients died of chordoma progression at 20, 14, and 10 months, respectively, after endoscopic treatment. One patient experienced two recurrences; the first was treated using a new endoscopic approach, whereas the second, 1 year later, was treated by means of a far lateral approach. Four patients underwent postoperative proton beam radiotherapy, whereas one underwent a conventional megavoltage x-radiation therapy. However, postoperative radiotherapy was not administered in the two patients treated for cranial base chondrosarcoma., Conclusion: The flexibility of this new technique with respect to the classical microscopic transsphenoidal approach permits us to widen the horizon of surgical management of aggressive cranial base tumors such as clival chordomas and chondrosarcomas.

Cavernous sinus surgery has always been a surgical challenge because of the high functional importance of this region and the associated high morbidity. The augmented peripheral vision of the endoscope has led to the development of surgical approaches that allow adequate exposure of the cavernous sinus, with a reduction in surgical morbidity. Since 1998, 65 patients with pituitary adenomas and intraoperative evidence of cavernous sinus invasion were treated with a purely endoscopic approach. Follow-up was of at least 6 (mean 51.2) months. There was no perioperative mortality and extremely low morbidity. Radical tumor removal was obtained in 21/35 cases with nonfunctioning adenomas. Hormonal remission was obtained in 13/30 functioning adenomas. One patient with partial hypopituitarism and 1 patient with persistent diabetes insipidus were seen. Three patients with delayed CSF leaks required endoscopic repair. In 1 patient with hemorrhagic infarction in a residual tumor, reintervention with craniotomy was necessary. We advocate the central role of surgery in the treatment of cavernous sinus tumors, since it allows definition of true cavernous sinus involvement, histopathological diagnosis and, when cure is not feasible, tumor volume reduction, which might be an important factor in the response to adjuvant therapy.

The progressive emergence of antimicrobial-resistant Gram-positive cocci especially in the setting of surgery and intensive care, recommends particular attention in making sound therapeutic choices to overcome both microbial resistances and haemato-encephalic barriers to effective local drug penetration. As in other Western countries, the occurrence of methicillin-resistant Staphylococcus aureus is particularly high also in Italy, especially when high-risk patients and/or settings are involved. In treating post-neurosurgical central nervous system infections (cerebral abscess and meningitis), a key issue is represented by the low cerebrospinal fluid concentration of the two available glycopeptide antibiotics (vancomycin and teicoplanin), usually recommended as first-line therapy of resistant Gram-positive cocci. Recent findings have focused on the possible role of linezolid, an oxazolidinone antibiotic, as a suitable candidate for the treatment of severe brain infection (abscesses) and post-neurosurgical infection, where treatment options and efficacy are significantly limited by the low glycopeptide transfer and the spread of glycopeptide-resistant bacterial strains. Three representative case reports (two brain abscesses and one post-surgical meningitis) are presented and discussed in light of the current literature: in all these cases, salvage linezolid treatment proved resolutory.