A cohort study of CNS tumors in Multiple Endocrine Neoplasia Type 1.

PURPOSE: Multiple Endocrine Neoplasia Type-1 (MEN1) is thought to increase the risk of meningioma and ependymoma. Hereby, we aimed to describe the frequency, the incidence and specific clinical and histological features of CNS tumors in the MEN1 population (except pituitary tumors). EXPERIMENTAL DESIGN: The study population included patients harboring CNS tumors diagnosed with MEN1 syndrome after 1990 and followed-up in the French MEN1 national cohort. Standardized incidence rate (SIR) was calculated based on the French Gironde CNS tumors registry. Genomic analyses were performed on somatic DNA from 7 CNS tumors including meningiomas and ependymomas from MEN1 patients, then in 50 sporadic meningiomas and ependymomas. RESULTS: Twenty-nine CNS tumors were found among the 1498 symptomatic patients (2%) (incidence=47.4/100'000 person-years; SIR=4.5), including 12 meningiomas (0.8%) (incidence=16.2/100'000; SIR=2.5), 8 ependymomas (0.5%) (incidence=10.8/100'000; SIR=17.6), 5 astrocytomas (0.3%) (incidence=6.7/100'000; SIR=5.8), and 4 schwannomas (0.3%) (incidence=5.4/100'000; SIR=12.7). Meningiomas in MEN1 patients were benign, mostly meningothelial, with 11 years earlier onset compared to the sporadic population and an F/M ratio of 1/1. Spinal and cranial ependymomas were mostly classified WHO grade 2. A biallelic MEN1 inactivation was observed in 4/5 ependymomas and 1/2 meningiomas from the MEN1 patients, whereas MEN1 deletion in one allele was present in respectively 3/41 and 0/9 sporadic meningiomas and ependymomas. CONCLUSIONS: Incidence of each CNS tumor was higher in the MEN1 population than in the French general population. Meningiomas and ependymomas should be considered part of the MEN1 syndrome, but somatic molecular data are missing to conclude for astrocytomas and schwannomas.

Is the OCT a predictive tool to assess visual impairment in optic chiasm compressing syndrome in pituitary macroadenoma? A prospective longitudinal study.

Visual dysfunction is a prevalent symptom in patients with non-functioning pituitary macroadenoma (NFPM); the role of OCT in such patients has not been yet determined. This is a prospective longitudinal observational study over a period of 6 years, on 20 patients presenting a radiological compression of the optic chiasma without visual acuity (VA) and visual field (VF) disturbances. The primary endpoint was to evaluate the impact of NFPA on neuro-axonal loss by measuring RNFL thickness using OCT at inclusion (T0), 12 months (T1), 24 months (T2), and 36 months (T3), respectively. The secondary endpoint was to monitor the evolution of OCT over time and assess any relationship between the degree of OCT alteration and the degree of radiological and clinical optic chiasm compression syndrome. Among the 20 patients included, eight (40%) showed an altered RNFL-OCT at diagnosis, while the remaining 12 (60%) showed a normal pattern. During a mean ophthalmologic follow-up of 60 months, 4 patients (20%) presented an asymptomatic reduction of RNFL-OCT thickness although all 20 had a VA/VF stable. To our knowledge, this study represents the first attempt to longitudinally evaluate the natural history and evolution of RNFL-OCT in patients with radiologically asymptomatic chiasmatic compression syndrome. The results do not clearly demonstrate the role of the OCT as an early prognostic factor for visual dysfunction.

Repeated Stereotactic Radiotherapy for Local Brain Metastases Failure or Distant Brain Recurrent: A Retrospective Study of 184 Patients.

BACKGROUND: The main advantages of stereotactic radiotherapy (SRT) are to delay whole-brain radiotherapy (WBRT) and to deliver ablative doses. Despite this efficacy, the risk of distant brain metastases (BM) one year after SRT ranges from 26% to 77% and 20 to 40% of patients required salvage treatment. The role and consequences of reirradiation remain unclear, particularly in terms of survival. The objective was to study overall survival (OS) and neurological death-free survival (NDFS) and to specify the prognostic factors of long-term survival. METHODS: we retrospectively reviewed the data of patients treated between 2010 and 2020 with at least two courses of SRT without previous WBRT. RESULTS: In total, 184 patients were treated for 915 BMs with two-to-six SRT sessions. Additional SRT sessions were provided for local (5.6%) or distant (94.4%) BM recurrence. The median number of BMs treated per SRT was one with a median of four BMs in total. The mean time between the two SRT sessions was 8.9 months (95%CI 7.7-10.1) and there was no significant difference in the delay between the two sessions. The 6-, 12- and 24-month NDFS rates were 97%, 82% and 52%, respectively. The 6-, 12- and 24-month OS rates were 91%, 70% and 38%, respectively. OS was statistically related to the number of SRT sessions (HR = 0.48; p < 0.01), recursive partitioning analysis (HR = 1.84; p = 0.01), salvage WBRT (HR = 0.48; p = 0.01) and brain metastasis velocity (high: HR = 13.83; p < 0.01; intermediate: HR = 4.93; p < 0.01). CONCLUSIONS: Lung cancer and melanoma were associated with a lower NDFS compared to breast cancer. A low KPS, a low number of SRT sessions, synchronous extracerebral metastases, synchronous BMs, extracerebral progression at SRT1, a high BMV grade, no WBRT and local recurrence were also associated with a lower NDFS. A high KPS at SRT1 and low BMV grade are prognostic factors for better OS, regardless of the number of BM recurrence events.

Second Cancer Affecting the Central Nervous System: Systematic Literature Review Exploring the Link Between Malignant Melanoma and Glioblastoma.

BACKGROUND: Glioblastoma (GBM) is a malignant primary brain cancer, among the most devastating and lethal diseases of the central nervous system. Similarly, malignant melanoma (MM) is responsible for most skin cancer-related deaths. A link between those 2 aggressive cancers has not yet been established. We present here a systematic review of the literature and an exemplificative case. METHODS: A systematic review of the literature was conducted to assess possible commonalities between MM and GBM. An exemplificative surgical vignette of a 73-year-old patient with the occurrence of a frontobasal GBM after surgical removal of a metastasis of MM in the same location was then detailed. RESULTS: Fifteen studies published in the English international literature support a link between MM and GBM, both based on epidemiologic and pathophysiologic/genetic aspects. This theory is reinforced by our surgical vignette of a collision tumor with the occurrence of both tumors in the same location several years apart. CONCLUSIONS: The evidence reported in the literature, as well as our surgical vignette, support a likely link between the pathogenesis of GBM and MM.

Approaching Intradural Lesions of the Anterior Foramen Magnum and Craniocervical Junction: Anatomical Comparison of the Open Posterolateral and Anterior Extended Endonasal Endoscopic Approaches.

BACKGROUND: Lesions of the foramen magnum (FM) and craniocervical junction area are traditionally managed surgically through anterior, anterolateral, and posterolateral skull-base approaches. This anatomical study aimed to compare the usefulness of a modified extended endoscopic approach, the so-called far-medial endonasal approach (FMEA), versus the traditional posterolateral far-lateral approach (FLA). METHODS: Ten fixed silicon-injected heads specimens were used in the Skull Base ENT-Neurosurgery Laboratory of the University Hospital of Strasbourg, France. A total of 20 FLAs and 10 FMEAs were realized. A high-resolution computed tomography scan was performed for quantitative analysis of the different approaches. The analysis aimed to estimate the extent of surgical exposure and freedom of movement (maneuverability) through the operating channel using a polygonal surface model to obtain a morphometric estimation of the area of interest (surface and volume) on postdissection computed tomography scans using Slicer 3D software. RESULTS: FMEA allows for a more direct route to the anterior FM, with wider brainstem exposure compared with the FLA and an excellent visualization of all anterior midline structures. The limitations of the FMEA include the deep and narrow surgical corridor and difficulty in reaching lesions located laterally over the jugular foramen and hypoglossal canal. CONCLUSIONS: The FMEA and FLA are both effective surgical routes to reach FM and craniocervical junction lesions. Modern skull base surgeons should have a good command of both because they appear complementary. This anatomical study provides the tools for comprehensive preoperative evaluations and selection of the most appropriate surgical approach.

Anatomical variations of the cavernous Internal Carotid Artery: Validation of an MRI-based classification.

OBJECTIVE: Variations of the cavernous Internal Carotid Artery (ICA) angulation (C4-bend) have been classified into 4 anatomical subtypes with particular surgical relevance, as a very angulated ICA comes in closest contact with the pituitary gland leading to higher risk of iatrogenic vascular injury. This study aimed to validate this classification using current routine imaging techniques. METHODS: The different cavernous ICA bending angles were measured on 109 MRI TOF sequences, within a retrospective database of patients with no sellar lesions. Each ICA was classified into one of 4 anatomical subtypes as already defined in a previous study [1]. Interrater agreement was assessed by a Kappa Correlation Coefficient. RESULTS: Kappa Correlation Coefficient was of 0.90 [0.82-0.95], validating the strong level of agreement between all observers when using the present classification. CONCLUSION: Classification of the cavernous ICA in 4 subtypes appears statistically valid on routinely used pre-operative MRI, providing an efficient tool to estimate the vascular iatrogenic risk prior to endoscopic endonasal transsphenoidal surgery.

Clipping Versus Coiling for Ruptured MCA Aneurysms Associated with Intracerebral Hematoma Requiring Surgical Evacuation.

BACKGROUND: Ruptured middle cerebral artery aneurysm (MCAa) can lead to intracerebral hematoma, and surgical evacuation can be performed in these cases. MCAa can be treated by clipping or before by endovascular therapy (EVT). Our objective was to compare the impact on the functional outcome of MCAa in patients with intracerebral hematoma requiring evacuation. METHODS: This is a multicenter, retrospective, cohort study with nine French neurosurgical units from January 1, 2013, to December 31, 2020. All participants were adult patients who required evacuation of an intracerebral hematoma. We looked for risk factors for poor outcomes by comparing the baseline characteristics and treatments performed by using the 6-month modified Rankin scale score. Poor outcomes were defined by an modified Rankin scale score of 3-6. RESULTS: A total of 162 patients were included. A total of 129 (79.6%) patients were treated by microsurgery, and 33 (20.4%) patients were treated by EVT. In multivariate analysis, factors associated with poor outcomes included hematoma volume, realization of a decompressive craniectomy, occurrence of procedure-related symptomatic cerebral ischemia, occurrence of delayed cerebral ischemia, and EVT. In the propensity score matching analysis (n = 33 per group), poor outcomes were observed in 30% of the patients in the clipping group versus 76% in the EVT group (P < 0.001). These differences may have been related to a longer delay between hospital admission and hematoma evacuation in the EVT group. CONCLUSIONS: In the specific subgroup of ruptured MCAa with intracerebral hematoma that requires surgical evacuation, clipping with concomitant hematoma evacuation could provide better functional outcomes than EVT followed by surgical evacuation.

Pituitary Abscess: A Challenging Preoperative Diagnosis-A Multicenter Study.

Background and Objectives: Pituitary abscess (PA) is a rare occurrence, representing less than 1% of pituitary lesions, and is defined by the presence of an infected purulent collection within the sella turcica. Pas can be classified as either primary, when the underlying pituitary is normal prior to infection, or secondary, when there is associated a pre-existing sellar pathology (i.e., pituitary adenoma, Rathke's cleft cysts, or craniopharyngioma), with or without a recent history of surgery. Preoperative diagnosis, owing to both non-specific symptoms and imaging features, remains challenging. Treatment options include endonasal trans-sphenoidal pus evacuation, as well as culture and tailored antibiotic therapy. Methods: A retrospective multicenter study, conducted on a prospectively built database over a 20-year period, identified a large series of 84 patients harboring primary sellar abscess. The study aimed to identify crucial clinical and imaging features in order to accelerate appropriate management. Results: The most common clinical presentation was a symptom triad consisting of various degrees of asthenia (75%), visual impairment (71%), and headache (50%). Diagnosis was achieved in 95% of cases peri- or postoperatively. Functional recovery was good for visual disturbances and headache. Pituitary function recovery remained very poor (23%), whereas the preoperative diagnosis represented a protective factor. Conclusions: In light of the high prevalence of pituitary dysfunction following the management of PAs, early diagnosis and treatment might represent a crucial issue. Currently, there are no standard investigations to establish a conclusive preoperative diagnosis; however, new, emerging imaging methods, in particular nuclear imaging modalities, represent a very promising tool, whose potential warrants further investigations.

p16 Immunohistochemical Expression as a Surrogate Assessment of CDKN2A Alteration in Gliomas Leading to Prognostic Significances.

CDKN2A is a tumor suppressor gene encoding the p16 protein, a key regulator of the cell cycle. CDKN2A homozygous deletion is a central prognostic factor for numerous tumors and can be detected by several techniques. This study aims to evaluate the extent to which immunohistochemical levels of p16 expression may provide information about CDKN2A deletion. A retrospective study was conducted in 173 gliomas of all types, using p16 IHC and CDKN2A fluorescent in situ hybridization. Survival analyses were performed to assess the prognostic impact of p16 expression and CDKN2A deletion on patient outcomes. Three patterns of p16 expression were observed: absence of expression, focal expression, and overexpression. Absence of p16 expression was correlated with worse outcomes. p16 overexpression was associated with better prognoses in MAPK-induced tumors, but with worse survival in IDH-wt glioblastomas. CDKN2A homozygous deletion predicted worse outcomes in the overall patient population, particularly in IDH-mutant 1p/19q oligodendrogliomas (grade 3). Finally, we observed a significant correlation between p16 immunohistochemical loss of expression and CDKN2A homozygosity. IHC has strong sensitivity and high negative predictive value, suggesting that p16 IHC might be a pertinent test to detect cases most likely harboring CDKN2A homozygous deletion.

Endoscopic-enhanced supra-cerebellar trans-tentorial (SCTT) approach to temporo-mesial region: a multicenter study.

Surgical access to the temporo-mesial area may be achieved by several routes such as the sub-temporal, the temporal trans-ventricular, the pterional/trans-sylvian, and the occipital interhemispheric approaches; nonetheless, none of them has shown to be superior to the others. The supra-cerebellar trans-tentorial approach allows a great exposure of the middle and posterior temporo-mesial region, while avoiding temporal lobe retraction. A prospective multicenter study was designed to collect data on patients undergoing endoscopic-enhanced SCTT approach to excise left temporo-mesial lesions. The study involved 5 different neurosurgical European centers and ran from 2015 to 2020. All patients had preoperative as well as postoperative brain MRI and ophthalmology evaluation. A total of 30 patients were included in this study, the mean follow-up was 44 months (range 18 to 84 months), male/female ratio was 16/14, and mean age was 39 years. A gross total resection was achieved in 29/30 (96.7%) cases. All surgical procedures were uneventful, without transient or permanent neurological deficits thanks to the preservation of the posterior cerebral artery. The endoscopic-enhanced SCTT approach provides satisfactory exposure to the left temporo-mesial region. Its minimally invasive nature helps minimize the surgical risks related to vascular and white tract manipulation, which represent known limitations of open microsurgical as well as other approaches.

Learning curve and influencing factors of performing microsurgical anastomosis: a laboratory prospective study.

Despite being a critical component of any cerebrovascular procedure, acquiring skills in microsurgical anastomosis is challenging for trainees. In this context, simulation models, especially laboratory training, enable trainees to master microsurgical techniques before performing real surgeries. The objective of this study was to identify the factors influencing the learning curve of microsurgical training. A prospective observational study was conducted during a 7-month diploma in microsurgical techniques carried out in the anatomy laboratory of the school of surgery. Training focused on end-to-end (ETE) and end-to-side (ETS) anastomoses performed on the abdominal aorta, vena cava, internal carotid and jugular vein, femoral artery and vein, caudal artery, etc. of Wistar strain rats under supervision of 2 expert anatomical trainers. Objective and subjective data were collected after each training session. The 44 microsurgical trainees enrolled in the course performed 1792 anastomoses (1577 ETE, 88%, vs. 215 ETS, 12%). The patency rate of 41% was independent from the trainees' surgical background and previous experience. The dissection and the temporary clamping time both significantly decreased over the months (p < 0.001). Technical mistakes were independently associated with thrombosis of the anastomoses, as assessed by the technical mistakes score (p < 0.01). The training duration (in weeks) at time of each anastomosis was the only significant predictor of permeability (p < 0.001). Training duration and technical mistakes constituted the two major factors driving the learning curve. Future studies should try and investigate other factors (such as access to wet laboratory, dedicated fellowships, mentoring during early years as junior consultant/attending) influencing the retention of surgical skills for our difficult and challenging discipline.

Efficacy of endoscopic management of primary central nervous system lymphoma: a multicentric study and literature review.

INTRODUCTION: To date, confined intra-ventricular localization of primary central nervous system lymphoma (PCNSL) has been usually managed with open surgical resection and/or stereotactic biopsy; nonetheless, the endoscopic approach to such localization can provide many advantages over standard microsurgery and/or stereotactic biopsy. Here we present our experience in managing such a rare pathology through the endoscopic approach. METHOD: In order to gather more information about such a rare pathology, a retrospective multicentric study on a prospectively built database has been performed during a 5 year period. Ten different European centers have been involved. RESULTS: A total of 60 patients, 25 women and 35 men, have been enrolled in the study. The mean age was 65.3 years. The mean lesion size was 40.3 mm. Among all selected patients, 40 (66.6%) had superficial lesions within the ventricle, whereas the remaining 20 (33.4%) had lesions involving/extending to deeper structures. All surgical procedures were uneventful and ETV was deemed necessary only in 20/60 cases. CONCLUSION: In our experience, endoscopic management of intraventricular PCNSL is an effective option. It should be considered after a careful examination of neurological and immunological status, alternative options for diagnostic sampling, location of the lesion, and presence or absence of hydrocephalus. Endoscopic management could be considered as a safe and minimally invasive option to obtain: (a) a biopsy sample of the lesion for further diagnostic workup, (b) CSF diversion through third ventriculostomy or VP shunt for the management of hydrocephalus, and (c) insertion of ventricular access devices for long term medical management and whenever necessary as a rescue option for ventricular tap.

A Laboratory Investigation on a Tailored Skin and Muscle Flap Variant for the Retrosigmoid Approach.

Introduction An anatomical study was conducted to test a modified C-shaped flap designed for patients undergoing a keyhole approach and/or minicraniotomy for retrosigmoid approach (KRSA). Materials and Methods Ten heads specimens were used. The surgical technique investigated was based on a 4-cm C-shaped skin incision with medial convexity (placed 8 cm laterally to the external occipital protuberance, with the lower edge terminating 1.5 to 2 cm above the mastoid tip), which followed by careful subperiosteal dissection and completed by reflecting and securing the skin flap layer anteriorly and the muscle flaps superiorly and inferiorly by stitches. Anatomical findings, including depth of surgical corridor till to the cerebellopontine cistern (CPC) as well as the sparing of neurovascular structures, were evaluated in every specimen. Results Twenty surgical approaches to CPC were conducted, resulting in a short working distance to the target (32 mm) without any need for a self-retaining retractor. In every specimen, the integrity of occipital muscles and cutaneous nerves was maintained, and a solid multilayer closure was always achieved. These data suggest that landmarks-based design of this C-shaped incision could be helpful in avoiding damages to the soft tissues encountered during KRSA. Conclusion This modified approach provides a wide surgical corridor to access the CPC while ensuring the minimal invasiveness of the standard S-shaped incision. Compared with the latter, it preserves better the integrity of the surrounding soft tissues and appears less likely to cause any iatrogenic injury to occipital muscles and cutaneous nerves.

Ellipsoid calculations versus manual tumor delineations for glioblastoma tumor volume evaluation.

In glioblastoma, the response to treatment assessment is essentially based on the 2D tumor size evolution but remains disputable. Volumetric approaches were evaluated for a more accurate estimation of tumor size. This study included 57 patients and compared two volume measurement methods to determine the size of different glioblastoma regions of interest: the contrast-enhancing area, the necrotic area, the gross target volume and the volume of the edema area. The two methods, the ellipsoid formula (the calculated method) and the manual delineation (the measured method) showed a high correlation to determine glioblastoma volume and a high agreement to classify patients assessment response to treatment according to RANO criteria. This study revealed that calculated and measured methods could be used in clinical practice to estimate glioblastoma volume size and to evaluate tumor size evolution.

Odontoid Type II fractures in elderly: what are the real management goals and how to best achieve them? A multicenter European study on functional outcome.

Odontoid fractures constitute the most common cervical fractures in elderly. External immobilization is the treatment of choice for Type I and III; there is still no wide consensus about the best management of Type II fractures. Observational multicenter study was conducted on a prospectively built database on elderly patients (> 75 years) with Type II odontoid fracture managed conservatively during the last 10 years. All patients underwent CT scan on admission and at 3 months; if indicated, selected patient had CT scan at 6 and 12 months. All patients were clinically evaluated by Neck Disability Index (NDI), Charlson Comorbidity Index (CCI), and American Society of Anaesthesiologists classification (ASA) on admission; NDI was assessed also at 6 weeks, 3, 6, 12, and 24 months; furthermore, a quality of life (QoL) assessment with the SF-12 form was performed at 3 and 12 months. Among the 260 patients enrolled, 177 (68%) were women and 83 (32%) men, with a median age of 83 years. Patients were followed up for a minimum of 24 months: 247 (95%) showed an excellent functional outcome within 6 weeks, among them 117 (45%) showed a good bony healing, whereas 130 (50%) healed in pseudo-arthrosis. The residual 5% were still variably symptomatic at 12 weeks; however, only 5 out of 13 (2% of the total cohort) required delayed surgery. This study showed that a conservative approach to odontoid Type II fracture in elderly is an effective and valid option, resulting in an excellent functional outcome (regardless of bony fusion) in the majority of cases. Failure of conservative treatment can be safely addressed with surgical fixation at a later stage.

Does interventional MRI-guided brain cryotherapy cause a blood-brain barrier disruption? Radiological analysis and perspectives.

Glioblastoma is the most common primary malignant brain tumor with an incidence of 5/100,000 inhabitants/year and a 5-year survival rate of 6.8%. Despite recent advances in the molecular biology understanding of glioblastoma, CNS chemotherapy remains challenging because of the impermeable blood-brain barrier (BBB). Interventional MRI-guided brain cryotherapy (IMRgC) is technique that creates a tissue lesion by making a severe targeted hypothermia and possibly a BBB disruption. This study goal was to analyze the effect of IMRgC on human BBB glioblastoma through its gadolinium enhancing features. All patients harboring a local glioblastoma recurrence and meeting all the inclusion criteria were consecutively included into this retrospective study during a 2-year period. The primary endpoint was to analyze the modification of the gadolinium enhancement on MRI T1 sequences using MR perfusion weighted images during follow-up. The secondary endpoint was to assess any ischemic/hemorrhagic complication following cryotherapy procedure using diffusion weighted imaging (DWI), susceptibility weighted imaging (SWI), or fluid-attenuated inversion recovery (FLAIR). Among the 6 patients studied, all (100%) showed a BBB disruption on the cryotherapy site through the analysis of the perfusion weighted images with an average delay of 2.83 months following the procedure. The gadolinium enhancement located around the cavity then spontaneously decreased in 4/6 patients (67%). No ischemic or hemorrhagic complication was recorded. This study confirms the IMRgC capacity to disrupt BBB as already suggested by the literature. IMRgC might represent a new option in the management of GBM allowing the combined effect of direct cryoablation and enhanced chemotherapy.

Pushing the boundaries of accuracy and reliability during stereotactic procedures: A prospective study on 526 biopsies comparing the frameless robotic and Image-Guided Surgery systems.

INTRODUCTION: A 12-year long, prospective, single center study was conducted, comparing two frameless systems for brain biopsies: ROSA robotic-assisted stereotaxy and BrainLab Varioguide image-guided stereotaxy (Image Guided Surgery, IGS). METHOD: All consecutive adult and pediatric patients undergoing frameless brain biopsies were included. Successfully achieving diagnosis was the primary endpoint, analysis of all periprocedural complications was the secondary endpoint, and the tertiary endpoint was the length of the procedure, with the aim of assessing of the learning curve for each operator over time. The results for the ROSA robot and the Varioguide system were compared and benchmarked to data from the literature. RESULTS: We performed 526 on 516 patients, 314 with the ROSA robot (Group A) and 212 with the IGS Varioguide (Group B). Histological diagnosis was achieved in 97.4% of cases in Group A, versus 93.3% in Group B (p < 0.05). No statistically significant difference was found for secondary and tertiary endpoints. The complication rate appeared similar between the 2 frameless systems, with a hemorrhagic complications rate of 3.5% in Group A and 4.7% in Group B. Permanent neurological deterioration was only recorded in 0.8% of cases from Group B. Mortality was recorded in 0.3% in Group A and 0.4% in Group B. CONCLUSION: This study provides evidence to confirm that robotic surgery lives up to its promises of increased safety, accuracy, and reliability.

Primary Endoscopic Endonasal Management of Giant Pituitary Adenomas: Outcome and Pitfalls from a Large Prospective Multicenter Experience.

PURPOSE: To evaluate factors influencing clinical and radiological outcome of extended endoscopic endonasal transtuberculum/transplanum approach (EEA-TTP) for giant pituitary adenomas (GPAs). METHODS: We recruited prospectively all consecutive GPAs patients undergoing EEA-TTP between 2015 and 2019 in 5 neurosurgical centers. Preoperative clinical and radiologic features, visual and hormonal outcomes, extent of resection (EoR), complications and recurrence rates were recorded and analyzed. RESULTS: Of 1169 patients treated for pituitary adenoma, 96 (8.2%) had GPAs. Seventy-eight (81.2%) patients had visual impairment, 12 (12.5%) had headaches, 3 (3.1%) had drowsiness due to hydrocephalus, and 53 (55.2%) had anterior pituitary insufficiency. EoR was gross or near-total in 46 (47.9%) and subtotal in 50 (52.1%) patients. Incomplete resection was associated with lateral suprasellar, intraventricular and/or cavernous sinus extension and with firm/fibrous consistence. At the last follow-up, all but one patient (77, 98.7%) with visual deficits improved. Headache improved in 8 (88.9%) and anterior pituitary function recovered in 27 (50.9%) patients. Recurrence rate was 16.7%, with 32 months mean recurrence-free survival. CONCLUSIONS: EEA-TTP is a valid option for GPAs and seems to provide better outcomes, lower rate of complications and higher EoR compared to one- or multi-stage microscopic, non-extended endoscopic transsphenoidal, and transcranial resections.

Role of hippocampal location and radiation dose in glioblastoma patients with hippocampal atrophy.

BACKGROUND: The hippocampus is a critical organ for irradiation. Thus, we explored changes in hippocampal volume according to the dose delivered and the location relative to the glioblastoma. METHODS: All patients were treated for glioblastoma with surgery, concomitant radiotherapy and temozolomide, and adjuvant temozolomide. Hippocampi were retrospectively delineated on three MRIs, performed at baseline, at the time of relapse, and on the last MRI available at the end of follow-up. A total of 98, 96, and 82 hippocampi were measured in the 49 patients included in the study, respectively. The patients were stratified into three subgroups according to the dose delivered to 40% of the hippocampus. In the group 1 (n = 6), the hippocampal D40% was < 7.4 Gy, in the group 2 (n = 13), only the Hcontra D40% was < 7.4 Gy, and in the group 3 (n = 30), the D40% for both hippocampi was > 7.4 Gy. RESULTS: Regardless of the time of measurement, homolateral hippocampal volumes were significantly lower than those contralateral to the tumor. Regardless of the side, the volumes at the last MRI were significantly lower than those measured at baseline. There was a significant correlation among the decrease in hippocampal volume regardless of its side, and Dmax (p = 0.001), D98% (p = 0.028) and D40% (p = 0.0002). After adjustment for the time of MRI, these correlations remained significant. According to the D40% and volume at MRIlast, the hippocampi decreased by 4 mm3/Gy overall. CONCLUSIONS: There was a significant relationship between the radiotherapy dose and decrease in hippocampal volume. However, at the lowest doses, the hippocampi seem to exhibit an adaptive increase in their volume, which could indicate a plasticity effect. Consequently, shielding at least one hippocampus by delivering the lowest possible dose is recommended so that cognitive function can be preserved. Trial registration Retrospectively registered.

Managing Incomplete and Complete Thoracolumbar Burst Fractures (AO Spine A3 and A4). Results from a Prospective Single-Center Study Comparing Posterior Percutaneous Instrumentation plus Mini-Open Anterolateral Fusion versus Single-Stage Posterior Instrumented Fusion.

OBJECTIVE: The treatment strategy for thoracolumbar burst fractures is still debated. The aim of this study is to evaluate clinical and radiologic outcomes of a 2-stage strategy with immediate posterior percutaneous instrumentation and delayed anterolateral fusion (group A) versus a single-stage open posterior instrumented fusion (group B). METHODS: Demographics and clinical and surgical data of patients operated for AO Spine A3 and A4 fractures were prospectively collected. Vertebral height and deformity were evaluated before and after surgery. Visual analog scale score for back pain, Oswestry Disability Index, and 12-Item Short Form Health Survey results for quality-of-life assessment were collected during follow-up. RESULTS: Among the 110 patients enrolled, 66 were allocated to group A and 44 to group B; the most common fractured level was T12 (34%). Postoperative complications were higher in group B, especially the wound infection rate (18% vs. 3%), and pseudomeningocele (14% vs. 0%). The 2-stage approach allowed an average long-term gain of 15.8° at the local kyphosis of fractured vertebra and 5.8° at the regional level (Cobb angle), versus 15.4° and 5.5° in group B. At 2 years follow-up, both groups showed significant functional improvements; however, the visual analog scale and Oswestry Disability Index metrics seemed more favorable for group A patients (P < 0.0001 vs. P < 0.003). A complete fusion rate was obtained in 100% of group A vs. 65% of group B. CONCLUSIONS: Our study indicates that percutaneous instrumentation and anterior fusion or an expandable cage lead to excellent long-term clinical and radiologic outcomes with a lower complication rate and higher fusion rate than those of open posterior approaches.