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Purpose: XLIF® is a widely used minimally invasive technique to treat different spine pathologies. The aim of this study was to quantify nerve distortion of lumbar plexus during XLIF® approach and to correlate it with morphometric data. Methods: Nine fresh frozen cadaveric specimens were used. All specimens were subjected to the same dissection procedure cored on a left XLIF® approach at L2/L3 and L4/L5 levels. Distortion of cutaneous superficial nerves, femoral nerve (FN) at L4/L5 and genitofemoral nerve (GN) at L2/L3 and L4/L5 while opening the retractor were assessed and analyzed with respect to psoas muscle features. Results: Superficial nerves were slightly displaced but never stretched. FN, as well as GN at L4/L5 level, could be displaced and stretched by the blades. Statistically significant correlation between FN distortion and the amount of psoas fibers interposed between the posterior blade of the retractor and the nerve itself (TCK) was found. GN distortion was found to be related to its clock position on an axial section of psoas muscle seen from cranially at L4/L5. Conclusion: FN was in close connection with the deep psoas muscle fibers and it is subjected to anterior translation that correlates with TCK. This mechanism may partly explain the rate of femoral nerve palsy that occurs despite neuromonitoring and safe entry zones respect. The GN location at L4/L5 should be considered not only for its projection in Zone I, but also for its clock position on the psoas muscle surface, since it affects its distortion. © 2016, Springer-Verlag Berlin Heidelberg.

OBJECTIVE Skull base chordomas (SBCs) are rare dysembryogenetic invasive tumors with a variable tendency for recurrence. According to previous studies, the recurrence rate seems to be affected by both clinical variables and tumor biological features. The authors present the results of treatment of SBCs in a large series of patients and investigate the role of 1p36 chromosomal region loss of heterozygosity (LOH) as a prognostic factor. METHODS Between 1990 and 2011, 45 patients were treated for SBCs. The mean follow-up was 76 months (range 1–240 months). An LOH analysis was performed in 27 cases. Survival analysis was performed to determine clinical and biological parameters correlating with clinical outcome. RESULTS The 5- and 10-year overall survival rates were 67% and 57%, respectively. Five- and 10-year progression-free survival rates were 58% and 44%, respectively. Multivariate analysis showed that extent of resection, adjuvant radiation therapy, and absence of rhinopharynx invasion were positive independent predictors of overall survival. The latter 2 variables and a younger patient age were positive independent predictors of progression-free survival. Twenty-one patients showed 1p36 LOH. All events of recurrence and death clustered in the group of patients with 1p36 LOH; however, this biological marker was not statistically significant on multivariate analysis. CONCLUSIONS Resection is the treatment of choice in primary and recurrent SBC. Patient age, rhinopharynx invasion at diagnosis, extent of tumor removal, and postoperative radiation therapy influence SBC prognosis. Genetic analysis, even while showing interesting results, did not reveal 1p36 LOH as an independent predictor of clinical outcome.

Haemangiopericytomas (HPCs) are rare tumours characterised by aggressive behaviour with tendency to local recurrence and to metastasise. WHO grade II and grade III tumours show different progression-free survival and overall survival rates. Gross total tumour resection is still considered the treatment of choice. Adjuvant radiation therapies represent an option in the treatment strategy regardless the extent of resection. Based on this consideration, Gamma Knife radiosurgery has been introduced either as a primary treatment or as an adjuvant treatment for residual or recurrent tumours. A systematic search was performed on PubMed, Web of Science and Google Scholar for clinical series reporting Gamma Knife radiosurgery, Cyberknife and Linear Accelerator (LINAC) for the management of intracranial HPCs. Fourteen studies focusing on the effects of Gamma Knife radiosurgery for intracranial HPCs were included. Four studies reported data on Cyberknife radiosurgery and LINAC. A total of 208 patients harbouring 366 tumours have been reported. Patient’s features, radiosurgical treatment characteristics and follow-up data of the pertinent literature have been critically revised. Gamma Knife radiosurgery and the other radiosurgical techniques represent a feasible and effective therapy in the management of HPCs. Tumour control and survival rate are comparable to those reported for radiotherapy. Further studies should be focused to define the exact role of Gamma Knife radiosurgery in the management of HPCs.

Purpose Granular cell tumors of the neurohypophysis are rare, solitary lesions, mostly presenting in the adult age. They rarely grow to a sufficient size to cause mass effect related symptoms and they may be found in most cases incidentally at autopsy. Because of their rarity as of now they have been described only as case reports or included in small clinical series. Methods We report a series of 11 patients, who underwent surgery for granular cell tumors of the neurohypophysis between 1996 and 2013 in a single center. Results Mean follow-up time after treatment was 92.2 months (range 9-231 months). Mean age at surgery was 40.7 years (range 12-66 years). There were 7 males (63.6 %) and 4 females (36.4 %). Main symptoms at presentation were: hyperprolactinemia (72.7 %), visual impairment (45.5 %) and headache (36 %). Except for 2 patients, all the others underwent surgery as primary treatment at our Institution, through a transsphenoidal (54.5 %) or a transcranial approach (45.5 %). Overall- and progression-free survival times for the entire series (calculated from the time of diagnosis) were 112.9 and 100.5 months respectively. There was one case of perioperative death in a patient who had undergone repeat transcranial surgery for residual tumor. Conclusions Although extremely rare, granular cell tumors of the neurohypophysis have to be considered in the differential diagnosis of suprasellar masses, to avoid misleading interpretation and consequent wrong therapeutic management. Early diagnosis, extensive tumor removal, opportune indication of adjuvant radiotherapy are the keys to manage these cases.

Background and Study Objective Several surgical approaches have been previously reported for the treatment of olfactory groove meningiomas (OGM). The trans-frontal-sinus subcranial approach (TFSSA) for the removal of large OGMs is described, comparing it with other reported approaches in terms of advantages and drawbacks. Material and Methods The TFSSA was performed on cadaveric specimens to illustrate the surgical technique. Results The surgical steps of the TFSSA and the related anatomical pictures are reported. The approach was adopted in a clinical setting; a case illustration is reported to demonstrate the feasibility of the described approach and to provide intraoperative pictures. Conclusion The TFSSA represents a possible route to treat large OGMs. The subcranial approach provides early devascularization of the tumor, direct tumor access from the base without traction on the frontal lobes, good overview of dissection of the optic nerves and anterior cerebral arteries, and dural reconstruction with pedicled pericranial flap.

Background and purpose Gamma Knife Surgery (GKS) can be an adjunctive option to surgery in the case of pituitary adenomas. The effect of dosimetric variables on the incidence of new anterior pituitary deficits after GKS requires better definition. Materials and methods This retrospective study considered 130 patients with a follow up after GKS >6months. The diagnosis was nonfunctioning pituitary adenoma (NFPA) in 68 patients and secreting pituitary adenoma (SPA) in 62 patients. Median margin dose was 15/25Gy for NFPA and SPA, respectively. The endocrinological median follow-up was 60months. Hypopituitarism was defined as a new pituitary deficit in (at least) one of the three hormonal axes (hypogonadism, hypothyroidism and hypoadrenalism). The predictive value of clinical/dosimetric parameters was tested by univariate/multivariate analyses. Results Sixteen patients (12.3%) showed a new pituitary deficit in one or more axes. Multivariate analysis confirmed that the mean dose to the stalk/pituitary and the amount of healthy tissue within the high dose region were strong independent predictors of pituitary dysfunction; their best cut-off values were around 15.7Gy, 7.3Gy and 1.4cm 3 , respectively. Conclusions Our data showed a dose-dependent incidence of new hormonal deficits after GKS for pituitary adenoma. During planning definition, the risk of hypopituitarism could be reduced using the outlined safe dose–volume values.

The surgical challenge of the treatment of tuberculum (TSMs) and diaphragma sellae meningiomas (DSMs) is to preserve or improve the visual function. Extradural and intradural optic nerve decompression should reduce surgical trauma of the nerve achieving a good visual result.We reported 37 consecutive TSMs and DSMs operated through fronto-temporo-orbito-zygomatic approach with extradural unroofing of the optical canal and early intradural incision of the dural sheath. Visual data were recorded measuring the visual impairment score (VIS), the visual acuity (VA), the visual field (VF) and the postoperative improvement.A good visual outcome (VIS improved or unchanged) was obtained in 97.2% of patients (35/36). The evaluation of 72 eyes showed a good outcome (VA and VF unchanged or improved) in 98.6% (71/72 eyes). The degree of preoperative VA and VF impairment was the only factor correlating with the postoperative improvement of VA (P.001 and P=.018) and VF defect (P.001). Worsening of visual function occurred in 1/37 patient (2.7%).Using this surgical technique we achieved a high improvement rate of visual defects and a low frequency of worsening.

The objective of the study was to evaluate the preoperative visual field defect, the postoperative outcome and the possible prognostic factors in patients with pituitary macroadenoma, using a quantitative method (the mean deviation = MD), and to review the literature. A total of 73 patients, operated trough trans-sphenoidal approach, were selected, and data in single eyes were analysed by calculating the frequency and the degree of postoperative improvement (relative improvement). The visual field defect improved in 95.7% of eyes: The recovery was complete in 48.9% and partial in 46.8%. Multivariate logistic regression showed that factors, independently predictive for complete recovery, were as follows: low preoperative MD absolute value (p = 0.008), low cranio-caudal diameter of tumour (p = 0.02) and young age (p = 0.0001). The mean relative improvement in visual field defect (dMD%) was correlated with the preoperative visual acuity (p = 0.0001) and inversely related with the preoperative MD (p = 0.007) and the age (p = 0.017). The relative improvement was higher in tumours with a smaller cranio-caudal diameter (p = 0.0185). In conclusion, using a quantitative method, we can measure the degree of the postoperative visual field defect improvement. Predictive factors for a complete recovery were good preoperative visual function, young age and low cranio-caudal tumour.

L’adenoma ipofisario aggressivo e caratterizzato dal punto di vista clinico da estensione e infiltrazione delle strutture anatomiche circostanti, crescita rapida e resistenza alle terapie standard sia mediche che chirurgiche. Istologicamente e stata introdotta alcuni anni fa la nozione di adenoma ipofisario atipico che dovrebbe identificare i tumori di comportamento clinico incerto. Tuttavia, non esiste una corrispondenza automatica fra l’adenoma aggresivo e quello atipico, il che rende complicato il paragone fra le varie casistiche anatomopatologiche e cliniche. Cio spiega anche l’obiettiva difficolta a paragonare le risposte terapeutiche e la prognosi a distanza di questi pazienti. Sarebbe pertanto auspicabile in futuro che le definizioni utilizzate per descrivere un adenoma ipofisario come aggressivo fossero piu omogenee e precise in modo da meglio definire protocolli diagnostici e terapeutici.

Object The authors describe a modified Le Fort I maxillotomy with medial and posterior antrectomy and removal of the pterygoid plates, aimed at improving the lateral surgical exposure during open transmaxillary surgery for pathological conditions involving the clivus. A cadaveric microanatomical study was conducted to compare the planimetric exposures allowed by the transmaxillary transpterygoid (TMTP) approach and the standard Le Fort I maxillotomy (STM). Methods Six cadaveric specimens that had been fixed with glutaraldehyde and injected with latex were dissected to obtain morphometric measurements after both TMTP and STM approaches. The anatomical areas exposed by the surgical approaches were calculated using ImageJ 1.37a software. Results As expected, the TMTP approach allowed for a greater surgical exposure, with an incremental area exposed ranging from 4.9 to 7.6 cm2 (mean ± standard deviation 6.4 ± 1.2 cm2, 95% CI 5.4–7.4 cm2). The amount of additional anatomical area visualized, as recorded as a percentage increase after the TMTP approach when compared with the STM approach, ranged from 83 to 109% (mean 99%). Conclusions The lateral surgical exposure allowed by the STM approach is limited by the pterygoid plates. The TMTP approach significantly improves the exposure of the anatomical regions lateral to the clivus, allowing access to the pterygopalatine and medial infratemporal fossae. In comparison with the STM, the TMTP approach allows for a surgical exposure that is nearly double. The authors conclude that the TMTP approach provides a significant improvement in the surgical exposure of the lateral paraclival areas, when compared with the STM approach.

Introduction With the goal of generate uniform criteria among centers dealing with pituitary tumors and to enhance patient care, the Pituitary Society decided to generate criteria for developing Pituitary Tumors Centers of Excellence (PTCOE). Methods To develop that task, a group of ten experts served as a Task Force and through two years of iterative work an initial draft was elaborated. This draft was discussed, modified and finally approved by the Board of Directors of the Pituitary Society. Such document was presented and debated at a specific session of the Congress of the Pituitary Society, Orlando 2017, and suggestions were incorporated. Finally the document was distributed to a large group of global experts that introduced further modifications with final endorsement. Results After five years of iterative work a document with the ideal criteria for a PTCOE is presented. Conclusions Acknowledging that very few centers in the world, if any, likely fulfill the requirements here presented, the document may be a tool to guide improvements of care delivery to patients with pituitary disorders. All these criteria must be accommodated to the regulations and organization of Health of a given country.

Background: Transsphenoidal surgery (TSS) is the treatment of choice for Cushing’s disease (CD). Postoperative hypercortisolemia mandates further therapy. Objective: The aim of the study was to characterize patients without immediate postoperative remission who have a delayed decrease to normal or low cortisol levels without further therapy. Design and Setting: A retrospective case series was conducted at three tertiary care centers. Patients and Intervention: We reviewed the records of 620 patients (512 females, 108 males; mean age, 38 ± 13 yr) who underwent transsphenoidal pituitary surgery for CD between 1982 and 2007. Results: Outcomes were classified into the following three groups based upon the postoperative pattern of cortisol testing: group IC (immediate control) included 437 of the 620 patients (70.5%) with hypocortisolism and/or cortisol normalization throughout the postoperative follow-up; group NC (no control) included 148 of 620 patients (23.9%) with persistent hypercortisolism; and group DC (delayed control) included 35 of 620 patients (5.6%) who had early elevated or normal UFC levels and developed a delayed and persistent cortisol decrease after an average of 38 ± 50 postoperative days. The total rate of recurrence was 13% at a median follow-up time of 66 months after TSS; the cumulative rate of recurrence at 4.5 yr was significantly higher in group DC vs. group IC (43 vs. 14%; P = 0.02). Conclusions: Hormonal assessment in the immediate postoperative period after TSS for CD may be misleading because delayed remission can occur in a subset of patients. Expectant management and retesting may spare some patients from unnecessary further treatment. Optimal timing to determine the need for further therapy after TSS remains to be determined.

Purpose: Cancer stem cells (CSC) have been isolated from human tumors, including glioblastoma multiforme (GBM). The aims of this study were the immunobiological characterization of GBM CSCs and the assessment of whether these cells represent suitable targets for immunotherapy. Experimental Design: GBM CSC lines and their fetal bovine serum (FBS)–cultured non-CSC pair lines were generated and examined by flow cytometry for expression of known tumor antigens, MHC-I and MHC-II molecules, antigen-processing machinery components, and NKG2D ligands. In addition, immunogenicity and immunosuppression of such cell lines for autologous or allogeneic T lymphocytes were tested by cytokine secretion (ELISPOT) or proliferation (carboxyfluorescein diacetate succinimidyl ester) assays, respectively. Results: Both GBM CSC and FBS lines were weakly positive and negative for MHC-I, MHC-II, and NKG2D ligand molecules, respectively. Antigen-processing machinery molecules were also defective in both cell types. Upregulation of most molecules was induced by IFNs or 5-Aza deoxycytidine, although more efficiently in FBS than in CSCs. Patient T-cell responses, mediated by both TH1 and the TH2 subsets, against autologous CSC could be induced in vitro. In addition, CSC but not their paired FBS tumor lines inhibited T-cell proliferation of healthy donors. Notably, a differential gene signature that was confirmed at the protein levels for some immunologic-related molecules was also found between CSC and FBS lines. Conclusions: These results indicate lower immunogenicity and higher suppressive activity of GBM CSC compared with FBS lines. The immunogenicity, however, could be rescued by immune modulation leading to anti-GBM T cell–mediated immune response. Clin Cancer Res; 16(3); 800–13

Background: The treatment of choice for Cushing’s disease is pituitary surgery. Second-line treatments include repeat pituitary surgery, radiation therapy, medical therapy, and bilateral adrenalectomy. The most used modalities to irradiate patients with Cushing’s disease include fractionated radiotherapy and single-dose Gamma Knife. We aim to review the efficacy and safety of radiotherapy in patients with persistent or recurring Cushing’s disease. Results: Remission of Cushing’s disease after radiotherapy ranges from 42 to 83%. There seems to be no clear difference according to the technique of radiation used. Most patients experience remission of disease within 3 years from treatment, with only few cases reaching normal cortisol secretion after a longer follow-up. Control of tumor growth varies from 93 to 100%. Severe side effects of radiotherapy, such as optic neuropathy and radionecrosis, are uncommon. New-onset hypopituitarism is the most frequent side effect of radiation, occurring in 30–50% of patients treated by fractionated radiotherapy while it has been reported in 11–22% of patients after Gamma Knife. Conclusion: Radiotherapy is an effective second-line treatment in patients with Cushing’s disease not cured by surgery. Consideration of the advantages and disadvantages of radiotherapy in comparison with other therapeutic options should always be carried out in the single patient before deciding the second-line therapeutic strategy for persisting or recurring Cushing’s disease.

PURPOSE: Pituitary macroadenomas with suprasellar extension present tight relationships with optic pathways; only one case of optic nerve penetration by a pituitary adenoma has been reported previously. METHODS: We report two cases of patients suffering from non-functioning pituitary macroadenomas with intra-operative findings of longitudinal splitting of the optic pathways. RESULTS: In both cases the patients were first operated on by a trans-sphenoidal route and the residual suprasellar tumour was resected by a transcranial surgery. CONCLUSION: The patients presented a good visual recovery, suggesting that the splitting of the optic pathways has not jeopardised the functional and anatomical integrity of the optic fibres in the reported cases

Purpose: To assess the utility of the Radiation Therapy Oncology Group Recursive Partitioning Analysis (RPA) and Score Index for Radiosurgery (SIR) stratification systems in predicting survival in patients with brain metastasis treated with Gamma Knife radiosurgery (GKRS). Methods and Materials: A total of 185 patients were included in the study. Patients were stratified according to RPA and SIR classes. The RPA and SIR classes, age, Karnofsky Performance Status (KPS), and systemic disease were correlated with survival. Results: Five patients were lost to follow-up. Median survival in patients in RPA Class 1 (30 patients) was 17 months; in Class 2 (140 patients), 10 months; and in Class 3 (10 patients), 3 months. Median survival in patients in SIR Class 1 (30 patients) was 3 months; in Class 2 (135 patients), 8 months; and in Class 3 (15 patients), 20 months. In univariate testing, age younger than 65 years (p = 0.0004), KPS higher than 70 (p = 0.0001), RPA class (p = 0.0078), SIR class (p = 0.0002), and control of the primary tumor (p = 0.02) were significantly associated with improved outcome. In multivariate analysis, KPS (p < 0.0001), SIR class (p = 0.0008), and RPA class (p = 0.03) had statistical value. Conclusions: This study supports the use of GKRS as a single-treatment modality in this selected group of patients. Stratification systems are useful in the estimation of patient eligibility for GKRS. A second-line treatment was necessary in 30% of patients to achieve distal or local brain control. This strategy is useful to control brain metastasis in long-surviving patients. (C) 2009 Elsevier Inc.

OBJECTIVE: Structural alterations in the microcirculation may be considered an important mechanism of organ damage. An increased media-to-lumen ratio of subcutaneous small resistance arteries has been demonstrated to predict the development of cardiocerebrovascular events in hypertensive patients. Alterations in the structure of small cerebral arteries have been demonstrated in animal models of experimental or genetic hypertension. However, no evaluation with reliable techniques has ever been performed in humans. DESIGN AND METHODS: Twenty-eight participants were included in the present study: they were 13 hypertensive patients and 15 normotensive individuals. All participants underwent a neurosurgical intervention for benign or malign tumors. A small portion of morphologically normal cerebral tissue was excised from surgical samples and examined. Cerebral small resistance arteries (relaxed diameter around 200 mum) were dissected and mounted on an isometric and isobaric myograph, and the tunica media to internal lumen ratio was measured. In addition, cerebral cortical microvessel density (MVD) was also evaluated. The tissue was sectioned and stained for CD31, and MVD was measured with an automated image analyzer (percentage of area stained). Blood pressure values were evaluated, before surgical intervention, by standard sphygmomanometry. RESULTS: M/L was significantly greater and MVD significantly lower in hypertensive patients than that in normotensive individuals. No difference between groups in collagen content or mechanical properties of cerebral small arteries was observed. CONCLUSION: Our results indicate that structural alterations of small cerebral vessels are present in hypertensive patients compared with normotensive individuals, similar to those previously observed in subcutaneous small arteries.

Context: Single-session stereotactic radiotherapy (SR) may be a potential adjuvant treatment in acromegaly. Objective: We analyzed the safety and efficacy of SR in patients who had previously received maximal surgical debulking at our center. Design: The study was a retrospective analysis of hormonal, radiological, and ophthalmologic data collected in a predefined protocol from 1994 through 2006. Setting: The study was performed at a university hospital. Patients: Eighty-three acromegalic patients, 52 women and 31 men, with a mean age of 42.6 ± 1.2 yr, participated in the study. The median follow-up was 69 months (interquartile range 44–107 months). Intervention: The patients were treated with SR for residual or recurrent GH-secreting adenoma. Main Outcome Measure: Normalization of age- and sex-adjusted IGF-I levels together with a basal GH level below 2.5 μg/liter without concomitant GH-suppressive drugs was the goal of therapy. Results: Fifty patients (60.2%) reached the main outcome of the study. The rate of remission was 52.6% at 5 yr [95% confidence interval (CI) 40.6–64.6%]. Another 13 patients (15.7%), who were resistant to somatostatin analogs, were in remission after SR. Multivariate analysis showed that low basal GH and IGF-I levels were associated with a favorable outcome. No serious side effects occurred after SR. The 5-yr cumulative risk of new onset hypogonadism, hypothyroidism, or hypoadrenalism was 3.6% (95% CI 0–8.6%), 3.3% (95% CI 0–7.7%), and 4.9% (95% CI 0–10.4%), respectively. Conclusion: In a highly selected group of acromegalic patients, SR treatment had good efficacy and safety. This may lead to reconsider the role of SR in the therapeutic algorithm of acromegaly.

Object The clinical outcome of patients with severe head injuries is still critically dependent on their secondary injuries. Although hypoxia and hypotension appear to mediate a substantial proportion of secondary injuries, many studies associate secondary brain injury with neuroinflammatory responses. Chemokines have been detected in the cerebrospinal fluid but not in the brain tissue of patients with head trauma. This study was performed to determine if chemokines were expressed in pericontusional brain tissue in patients with moderate or severe head trauma who underwent surgical evacuation of their brain contusions. Methods Twelve patients with posttraumatic cerebral contusion requiring a surgical evacuation were studied. A 20- to 40-mg sample of white matter was removed from the surgical cavity in the pericontusional area. Two patients undergoing elective surgery for clip ligation of an unruptured aneurysm were used as controls. The median interval from trauma to biopsy procedure was 44 hours (range 3–360 hours). Total RNA was isolated from these samples and a ribonuclease protection assay was performed to measure the mRNA levels of several chemokines: CCL2, CCL3, CCL4, CCL5, CXCL8, CXCL10, and XCL1. Results The CCL2, a monocyte chemoattractant produced by activated astrocytes, was the most strongly expressed chemokine, followed by CXCL8, CCL3, and CCL4. The chemokines CXCL10 and CCL5 were expressed at very low levels, and XCL1 was not detected. Conclusions Chemokine activation occurs early after moderate or severe head trauma and is maintained for several days after trauma. This event may contribute to neuroinflammatory exacerbation of posttraumatic brain damage in the pericontusional brain tissue.

Object Nonfunctioning pituitary adenomas (NFPAs) are benign tumors of the pituitary gland that typically cause visual and/or hormonal dysfunction. Surgery is the treatment of choice, but patients remain at risk for tumor recurrence for several years afterwards. The authors evaluate the early results of surgery and the long-term risk of tumor recurrence in patients with NFPAs. Methods Between 1990 and 2005, 491 previously untreated patients with NFPA underwent surgery at the Università Vita-Salute. Determinations of recurrence or growth of the residual tumor tissue during the follow-up period were based on neuroradiological criteria. Results Residual tumor after surgery was detected in 173 patients (36.4%). Multivariate analysis showed that invasion of the cavernous sinus, maximum tumor diameter, and absence of tumor apoplexy were associated with an unfavorable surgical outcome. At least 2 sets of follow-up neuroimaging studies were obtained in 436 patients (median follow-up 53 months). Tumors recurred in 83 patients (19.0%). When tumor removal appeared complete, younger age at surgery was associated with a risk of tumor recurrence. In patients with incomplete tumor removal, adjunctive postoperative radiotherapy had a marked protective effect against growth of residual tumor. Conclusions Complete surgical removal of NFPAs can be safely achieved in > 50% of cases. Visual symptoms and, less frequently, pituitary function may improve after surgery. However, tumor can recur in patients after apparently complete surgical removal. In patients with incomplete tumor removal, radiation therapy is the most effective adjuvant therapy for preventing residual tumor growth.

Objective: Giant pituitary adenomas, defined as those measuring at least 4 cm in maximum diameter, are a therapeutic challenge. We report our experience in a large, consecutive series of patients with giant adenomas. Methods: Between 1990 and 2004, 95 patients with a giant pituitary adenomas underwent surgery at our department. Nonfunctioning pituitary adenoma was the most frequent type (n = 70; 73.7%), whereas hormone-secreting adenomas numbered only 25 (26.3%). The mean age at the time of surgery (+/- standard error of the mean) was 48.4 +/- 1.5 years; there were 66 men (69.5%) and 29 women (20.5%). Results: In total, 111 surgical procedures were performed. Of these, 85 approaches (76.6%) were transsphenoidal and 26 (23.4%) were transcranial. Visual improvement occurred in 59 of the 79 patients with preoperative defect who could be evaluated after surgery (74.7%). Radical tumor excision was obtained in 14 patients (14.7%). Adjuvant medical and radiation therapies led to 74.5% (95% confidence interval, 62.7-86.4%) control of tumor growth at 5 years. This was not different in patients with nonfunctioning pituitary adenomas compared with patients with hormone-secreting tumors. In the subgroup of patients with nonfunctioning pituitary adenomas, radiation therapy had a protective role against tumor growth (P < 0.01). Conclusion: Maximal surgical removal of giant adenomas through the transsphenoidal or transcranial approach, or both, aimed to relieve compression of the optic pathway and reduce tumor volume as much as possible, offers the best chances to control the tumor when followed with adjuvant medical and radiation therapies.

The pterygopalatine fossa (PPF) is a small anatomic region of particular interest in cranial base surgery. Infectious diseases and malignancy may spread through the PPF to contiguous areas as a result of the low resistance offered by the numerous foramina and fissures that surrounds the fossa. We present an anatomic report on the PPF. Twelve sides of six fixed cadaveric heads were dissected through a LeFort I maxillary osteotomy with transantral exposure of the neurovascular content of the PPF. Arterial vascular patterns of the maxillary artery were observed. The pterygopalatine fossa is a deeply located small anatomic region with a rich neurovascular content. The third portion of the maxillary artery in the PPF may demonstrate a variable vascular morphology. A correct understanding and knowledge of the anatomic structures lodged into the PPF, as well as their relationships and functions, remain crucial to minimizing postsurgical morbidity and intraoperative complications.

Patients with a thyrotropin-secreting pituitary adenoma (TSHoma) are exposed to unregulated and inappropriately high levels of thyrotropin (TSH). Given the rarity of this condition, it is not known whether this chronic TSH stimulation of the thyroid gland might represent a risk factor for the development of differentiated thyroid cancer (DTC). We analyzed the incidence of DTC in a large cohort of patients with TSHomas.The study population consisted of all consecutive patients who underwent neurosurgery for a TSHoma between 1990 and 2013. Criteria for the diagnosis of TSHoma in patients without previous thyroid ablative procedures included elevated free thyroid hormones and normal/high serum TSH concentrations, presence of a lesion at magnetic resonance imaging (MRI), and abnormal response of TSH to at least one dynamic test. Patients who had received thyroid ablative procedures were required to have a pituitary lesion on MRI and TSH levels not suppressed while on levothyroxine therapy at doses causing elevation of free thyroid hormone levels.Sixty-two patients (32 females, 30 males) underwent surgery for a TSHoma at our center. Among them, 3 patients had a coexistent diagnosis of DTC with an estimated incidence of 4.8%. In 2 patients, DTC was diagnosed during the evaluation for suspected TSH-dependent hyperthyroidism, whereas in the third patient, diagnosis of DTC preceded the detection of the pituitary tumor.The elevated incidence of DTC in patients with TSHoma suggests a possible role of TSH hypersecretion in the development of thyroid tumors. A formal high-resolution ultrasound of the thyroid is recommended in patients diagnosed with a TSHoma, especially if a long history of the pituitary tumor is suspected. Moreover, suspicion about the presence of TSHoma should be raised by the lack of suppression of TSH levels despite adequate doses of levothyroxine after thyroidectomy for DTC.

Intraventricular tumors present difficult challenges to the neurosurgeon. Neurosurgeons have begun to explore the possibilities of the endoscope in the complete resection of solid intraventricular tumors. The learning curve is considered steep when dealing with such lesions endoscopically. The aim of this study was to develop a laboratory training model for pathological intraventricular neuroendoscopic surgery. Thirty formalin-fixated, latex-injected cadaveric heads were used. The contrast-enhancing tumor polymer, Stratathane resin ST-504 derived polymer (SRSDP), was injected into the lateral ventricle via Frazer’s point under direct endoscopic visualization and real-time fluoroscopic guidance. Neurosurgeon participants at a ventricular endoscopic course then performed an endoscopic approach to the intraventricular tumor model lesion via an ipsilateral frontal burr hole. The properties of the SRSDP mixture could be manipulated through varying concentrations of source materials in order to achieve a desired consistency and allow for piecemeal resection. Tumor could be injected into the lateral and third ventricles. The tumor model allowed participants to compare both normal and pathological endoscopic anatomy in the one specimen. Our novel injectable tumor model can assist neurosurgeons preparing themselves for the challenges associated with a piecemeal resection of a solid lesion in the lateral or third ventricle.

Background: Spinal cord stimulation (SCS) is a technique used worldwide to treat several types of chronic neuropathic pain refractory to any conservative treatment. The aim of this data collection is to enforce evidence of SCS effectiveness on neuropathic chronic pain reported in the literature and to speculate on the usefulness of the trial period in determining the long–term efficacy. Moreover, the very low percentage of undesired side effects and complications reported in our case series suggests that all implants should be performed by similarly well-trained and experienced professionals. Method: A multicentric data collection on a common database from 11 Italian neurosurgical departments started 3 years ago. Two different types of electrodes (paddle or percutaneous leads) were used. Of 122 patients, 73 % (N = 89) were submitted to a trial period, while the remaining patients underwent the immediate permanent implant (N = 33). Statistical comparisons of continuous variables between groups were performed. Results: Most of the patients (80 %) had predominant pain to their lower limbs, while only 17 % of patients had prevalent axial pain. Significant reduction in pain, as measured by variation in visual analogue scale (VAS) score, was observed at least 1 year after implantation in 63.8 % of the cases, 59.5 % of patients who underwent a test trial and 71.4 % of patients who underwent permanent implant at once. No statistical differences were found between the lower-limb pain group and the axial pain group. Conclusions: No relevant differences in long-term outcomes were observed in previously tested patients compared with patients implanted at once. Through this analysis we hope to recruit new centres, to give more scientific value to our results. © 2015, Springer-Verlag Wien

Objective: TSH-secreting pituitary adenomas account for about 1-2% of all pituitary adenomas. Their diagnosis may be very difficult when coexistence of other diseases masquerades the clinical and biochemical manifestations of TSH-hypersecretion. Clinical presentation: A 41-yr-old female patient, weighing 56 kg, was referred for evaluation of an intra- and suprasellar mass causing menstrual irregularities. Eight yr before, the patient had been given a diagnosis of subclinical autoimmune hypothyroidism because of slightly elevated TSH levels and low-normal free T-4 (FT4). Menses were normal. Despite increasing doses of levo-T-4 (L-T-4; up to 125 mu g/day), TSH levels remained elevated and the patient developed mild symptoms of hyperthyroidism. After 7 yr, the menstrual cycle ceased. Gonadotropins were normal, whereas PRL level was elevated at 70 mu g/l and magnetic resonance imaging (MRI) of the hypothalamic-pituitary region revealed a pituitary lesion with slight suprasellar extension. The tumor was surgically removed and histological examinations revealed a pituitary adenoma strongly positive for TSH. Three months after surgery the patient was well while receiving L-T-4g 75 mu g/day and normal menses had resumed. MRI of the hypothalamic-pituitary region showed no evidence of residual tumor. At the last follow-up, 16 months after surgery, serum TSH, free T-3 (FT3), and FT4 levels were normal. Conclusions: Coexistence of autoimmune hypothyroidism and TSH-secreting pituitary adenoma may cause further delays in the diagnosis of the latter. In patients with autoimmune hypothyroidism, one should be aware of the possible presence of a TSH-secreting pituitary adenoma when TSH levels do not adequately suppress in the face of high doses of L-T-4 replacement therapy and elevated serum thyroid hormone levels.

OBJECTIVES: The aim of the study was to correlate the Ki-67 and cyclin A labelling index (LI) with clinical characteristics and risk of recurrence of craniopharyngiomas. METHODS: 47 consecutive patients were studied, 21 female and 26 male, aged 34.3 (2.8) years. Immunohistochemical analysis was performed on paraffin wax embedded material using monoclonal antibodies directed against the proliferation associated nuclear antigen Ki-67 and cyclin A. RESULTS: The median Ki-67 LI was 8.6% (interquartile range, 4.4%-14.0%). Ki-67 LI was significantly higher in tumours with a heavy inflammatory reaction and diabetes insipidus at presentation, whereas other clinical and histological features were not associated with the proliferation index. There was a strong linear correlation between Ki-67 LI and cyclin A LI (r = 0.77; p

Various cytogenetic and molecular findings indicate 1p36 loss as a consistent change in sporadic and inherited chordoma, a rare embryogenetic neoplasm arising from notochord remnants. We studied 27 sporadic chordomas by means of loss of heterozygosity (LOH) of 31 microsatellites localized to the 1p36.32-36.11 region, and restricted the minimal LOH interval shared by 85% of the tumours to 1p36.13. We also used RT-PCR analysis to investigate the role of the candidate genes CASP9, EPH2A, PAX7, DAN and DVL1, which were selected on the basis of the physical mapping of the LOH region and their plausible oncosuppressor function. RT-PCR analysis showed the presence of DAN and PAX7 transcript fragments of the expected size in all of 8 chordoma samples, whereas the CASP9-specific fragment was observed in only 3 and EPH2A was absent in one. Smaller than expected DVL1 transcripts were found in 4 tumours as well as in their normal counterpart (nucleus pulposus), which also showed a typically sized transcript. Sequencing revealed the skipping of 3 exons in the smallest DVL1 fragment, thus leading to a frameshift and predicting a truncated DVL1 gene product. Our study of the largest cohort of chordoma patients recruited so far indicates a common molecular lesion at 1p36.13, and suggests that the CASP9, EPH2A and DVL1 genes may play an onco-suppressing role and be involved in the development of chordoma.

Transcranial approaches to pituitary tumors were proposed by the pioneers of neurosurgery and are still adopted with different modifications in selected cases. The main goal of this surgery is to decompress the optic pathways. The kind of approach is mainly dictated by the dimension, location, and consistency of the tumor mass and by other coexistent vascular pathologies. The transcranial approaches most frequently adopted are grouped as fronto-pterional, transfrontal, and combined approaches. This article reviews the indications for each transcranial approach. Moreover, the transcranial approaches to pituitary tumors are described in detail, stressing technical aspects and the prevention of complications. Particular attention is given to the fronto-orbitozygomatic (FTOZ) approach with intradural and extradural decompression of the optic nerve. This approach is the one most frequently used in our recent experience. Results are encouraging in particular in terms of postoperative visual function. Complications related to these procedures and their perioperative management are also reported.

Medical therapy with dopaminergic drugs is the preferred initial treatment for symptomatic prolactin (PRL)-secreting adenomas; but in recent years, there has been a renewed interest in surgery. The aim of this study is to report a large series of patients operated for prolactinoma in the last 10 yr. A total of 120 consecutive patients (93 female, 27 male) underwent surgery from January 1990 to December 1999. Their mean age at surgery was 29.7 +/- 0.9 yr. Fifty-nine patients (49.2%) had a microadenoma, and the remaining 61 (50.8%) had a macroadenoma, of which 24 (20%) were intrasellar and 37 (30.8%) were extrasellar adenoma. Magnetic resonance imaging signs of invasion of the cavernous sinus were detected in 18 patients (15.0%). Thirty-one patients (25.8%) had never been treated before, whereas the remaining 89 (74.2%) had received dopaminergic drugs. After surgery, normalization of PRL levels occurred in 77 patients (64.2%). Logistic regression analysis showed that the only predictive factor of unsuccessful surgery was a high preoperative PRL level. Recurrence of hyperprolactinemia occurred in 13 of the 77 cured patients (16.9%) during a mean follow-up of 50.2 +/- 3.0 months; the 5-yr disease-free survival was 75.9%. Extrasellar extension of the tumor and presence of a postoperative PRL response to TRH were associated with a lower risk of relapse. In summary, surgery normalized PRL levels and relieved symptoms of hyperprolactinemia in most patients. Recurrence of hyperprolactinemia occurred within 4 yr after surgery. Transsphenoidal surgery can be offered as a definitive therapy, especially to patients with intrasellar tumors.

Since the 1990 s, Gamma Knife radiosurgery (GKRS) has become the first-line treatment option for small- to medium-size vestibular schwannomas (VSs), especially in patients without mass effect-related symptoms and with functional hearing. The aim of this study was to assess the safety and efficacy of GKRS, in terms of tumor control, hearing preservation, and complications, in a series of 379 consecutive patients treated for VS.Of 523 patients treated at the authors' institution for VS between 2001 and 2010, the authors included 379 who underwent GKRS as the primary treatment. These patients were not affected by Type 2 neurofibromatosis and had clinical follow-up of at least 36 months. Clinical follow-up (mean and median 75.7 and 69.5 months, respectively) was performed for all patients, whereas audiometric and quantitative radiological follow-up examinations were obtained for only 153 and 219 patients, respectively. The patients' ages ranged from 23 to 85 years (mean 59 years). The mean tumor volume was 1.94 ± 2.2 cm(3) (median 1.2 cm(3), range 0.013-14.3 cm(3)), and the median margin dose was 13 Gy (range 11-15 Gy). Parameters considered as determinants of the clinical outcome were long-term tumor control, hearing preservation, and complications. A statistical analysis was performed to correlate clinical outcomes with the radiological features of the tumor, dose-planning parameters, and patient characteristics.Control of the tumor with GKRS was achieved in 97.1% of the patients. In 82.7% of the patients, the tumor volume had decreased at the last follow-up, with a mean relative reduction of 34.1%. The rate of complications was very low, with most consisting of a transient worsening of preexisting symptoms. Patients who had vertigo, balance disorders, or facial or trigeminal impairment usually experienced a complete or at least significant symptom relief after treatment. However, no significant improvement was observed in patients previously reporting tinnitus. The overall rate of preservation of functional hearing at the long-term follow-up was 49%; in patients with hearing classified as Gardner-Robertson (GR) Class I, this value was 71% and reached 93% among cases of GR Class I hearing in patients younger than 55 years.Gamma Knife radiosurgery is a safe and effective treatment for VS, achieving tumor control in 97.1% of cases and resulting in a very low morbidity rate. Younger GR Class I patients had a significantly higher probability of retaining functional hearing even at the 10-year follow-up; for this reason, the time between symptom onset, diagnosis, and treatment should be shortened to achieve better outcomes in functional hearing preservation.

Background: Solitary non-chordomatous lesions of the clivus are rare pathologies, which represent a diagnostic challenge. This study provides an overview of the clinical, radiological and prognostic characteristics of non-chordomatous clival lesions, highlighting current therapeutic options. Methods: Twenty-two non-chordomatous lesions of the clivus were collected. A retrospective analysis of clinical and radiological patterns as well as survival data was conducted. Results: Clinical presentation was a result of local mass effect. Imaging features, although mainly specific, were not always diagnostic. Extent of surgery was gross total in 45.5 % of cases. Depending on the histology, biological behaviour and presence of seeding, adjuvant treatment was performed, tailoring the treatment strategy to the single patient. Conclusions: Solitary non-chordomatous lesions of the clival bone are more prevalent than expected. They should be approached with a correct differential diagnosis, considering specific epidemiological, radiological, and histopathological characteristics, to minimise diagnostic bias and allow the planning of the best treatment strategy. © 2015, Springer-Verlag Wien.

Our aim was to prospectively analyze the use of contrast-enhanced ultrasound (CEUS) in the quantitative assessment of the response of uveal melanoma (UM) to gamma-knife radiosurgery (GKR), investigating whether changes in tumor vascularization precede thickness reduction, which on average occurs at 12 months after GKR.Ten patients with UM treated with GKR underwent sonography (US) and CEUS at baseline and at 3, 6, and 12 months after GKR. The transverse diameter, thickness, and quantitative parameters of the UM (ie, area under the curve in the wash-in phase, wash-in perfusion index, peak enhancement, and wash-in rate) were calculated by using dedicated software and compared by using Wilcoxon's signed-rank test.The mean tumor thickness on US was significantly less at both 6 (6.6 mm) and 12 months after GKR (5.8 mm) than it was at baseline (8.3 mm; p 0.05, both comparisons). Compared with baseline data, the median flow quantitative parameters on CEUS were significantly changed as follows: the peak enhancement (in arbitrary units [au]) at baseline was 5 × 10(6) ; 6 months after GKR, it was 2 × 10(1) (p 0.05), and 12 months after GKR, it was 4 × 10(1) (p0.05). The wash-in rate (in au) at baseline was 1 × 10(6) ; 6 months after GKR, it was 2.1 (p 0.05), and 12 months after GKR, it was 9.3 (p 0.05). The wash-in perfusion index (in au) at baseline was 2 × 10(7) ; 6 months after GKR, it was 7 × 10(1) (p 0.05), and 12 months after GKR, it was 1 × 10(2) (p 0.05). The area under the curve during the wash-in phase (in au) at baseline was 1 × 10(8) ; 12 months after GKR, it was reduced to 6 × 10(2) (p 0.05).At 6 months after GKR, a reduction of tumor thickness, as detected on US, occurred in 6 of the 10 patients, whereas a reduction in all the quantitative parameters measured on CEUS occurred in all 10 patients. However, a larger population is needed to investigate whether CEUS could become the first-choice technique for monitoring the response of UM to GKR.

Object The drilling of the suprameatal bone during the retrosigmoid intradural suprameatal approach (RISA) puts the superior petrosal vein complex at risk of heating and mechanical injury, which may lead to cerebellar swelling and infarction. We present a new technique to protect the superior petrosal venous complex during suprameatal bone drilling. Material and methods A microanatomical laboratory investigation on cadaver was conducted. The surgical technique is described and intraoperative schematic pictures are provided. Results The surgical steps of this technique and the related intraoperative images are reported. One case illustration regarding the removal of a large petrous apex meningioma with Meckel cave extension is described to demonstrate the application of the technique in a clinical setting. Conclusions Reflecting a dural flap onto the posterior trigeminal nerve root and the superior petrosal vein complex can be a simple way to protect the nerve and the vein during the suprameatal bone drilling during the RISA. © 2014 Georg Thieme Verlag KG Stuttgart New York.

Giant Hemorrhagic Cervical Schwannoma in a Young Woman with Acute Quadriparesis: Case Report Schwannomas are the most common extramedullary spinal tumors. The acute hemorrhagic onset of a spinal schwannoma is a rare occurrence.We report the case of a 32-year-old woman who presents with acute onset of quadriparesis due to a hemorrhagic intradural schwannoma. The tumor arose from left C1-C2 roots and extended downward from C1 to C5 vertebral levels. An emergency posterior osteoplastic laminotomy extending from C2 to C4 was performed anden bloc resection of the tumor was achieved. Histological diagnosis was schwannoma with hemorrhagic components.

Objective: Our objective was to describe the effects of surgery and radiotherapy on hormonal control and tumor mass in short- and long-term follow-up of TSH-secreting pituitary adenomas (TSHomas). Methods: This was a retrospective multicenter study. Results: We collected data of 70 TSHomas (70% macroadenomas). The mean follow-up was 64.4 (range 3-324) months. Overall, 97% of patients were treated with surgery; in 27% of them radiotherapy was associated. After surgery, 75% of patients normalized thyroid function, 58% normalized both pituitary imagingandhormonal profile,9%developed pituitary deficiencies,and3% had tumor or hormonal recurrence, all within the first 2 years after surgery. Presurgical medical treatment did not significantly improve surgical outcome (63% vs 57%). Radiotherapy controlled hypersecretion in37%of patients within 2 years, whereas32%of patients developednewpituitary deficiencies from 18 to 96 months from treatment. At last follow-up, 80% of patients normalized thyroid function, whereas 20% were currently on medical treatment: 85% with somatostatin analog (SSA) alone and 15% with SSA combined with methimazole. Subjects who achieved disease control had surgery as the only treatment in 80% of cases and surgery combined with irradiation in 20%. Conclusions: Surgery remains the first-choice treatment for TSHoma. If surgery is successful, recurrence is rare. When surgery is unsuccessful or contraindicated, SSA and radiotherapy are effective in controlling hyperthyroidism and tumor growth in the majority of patients. The effects of radiotherapy on TSH secretion and tumor mass are greater within the first years after treatment, whereas pituitary deficiencies may occur several years later. © 2014 by the Endocrine Society.

To investigate the effects of octreotide administration on the growth rate of GH-secreting pituitary adenomas, we measured both the Ki-67 labeling index (LI) and the apoptotic index in tumor specimens from octreotide-treated or matched untreated acromegalic patients. Thirty-nine patients who received octreotide until the day of or the day before surgery and 39 untreated patients matched for sex, age, tumor size, extension, and invasiveness were studied. Immunocytochemical analysis was performed on paraffin-embedded material using a monoclonal antibody (MIB-1) directed against a proliferation-associated nuclear antigen, Ki-67, to measure the growth fraction. Apoptosis was assessed by the terminal deoxynucleotidyl transferase-mediated deoxy-UTP nick endlabeling method, using a monoclonal antibody recognizing areas of DNA fragmentation. The Ki-67 LI and apoptosis were counted on separate slides in at least 1000 evaluable cells. Octreotide-treated patients showed a lower Ki-67 LI (1.8 ± 0.3%) than untreated controls (3.8 ± 0.7%; P < 0.02). Overall, the mean Ki-67 LI of treated patients was 53% lower than that in untreated patients. The antiproliferative effect of octreotide occurred independently of tumor extension and invasiveness. Octreotide-treated and untreated patients showed similar apoptotic indexes (0.6 ± 0.2% and 0.8 ± 0.3%, respectively). There was a positive correlation between the Ki-67 LI and the apoptotic index (r = 0.29; P< 0.03). Our study demonstrates that acromegalic patients receiving chronic octreotide treatment have a lower value of the proliferation marker Ki-67, but no significant difference in the apoptotic index compared with matched untreated patients. The antiproliferative effect of octreotide on GH-secreting adenomas should imply a lower risk of tumor growth during long-term chronic treatment with the drug.

OBJECTIVE The desmopressin test has been proposed as a useful tool for the differential diagnosis of Cushing's disease. The aim of our study was to investigate, in a large series of patients with Cushing's disease, the incidence of a positive ACTH and cortisol response to desmopressin. Moreover, we repeated the test soon after surgery to verify its usefulness in the assessment of early and late surgical results. PATIENTS AND METHODS One hundred and seven consecutive patients with Cushing's disease, 89 female and 18 male patients, with a mean age of 37·2 ± 1·3 years, were studied. All patients, except three, repeated the test 5–6 days after surgery. Desmopressin (10 µg) was injected i.v. and blood samples were drawn 15, 30, 45 and 60 minutes thereafter. Plasma ACTH and serum cortisol were measured in duplicate by commercially available immunoassays. A positive response to desmopressin was considered to be a plasma ACTH and serum cortisol increment of at least 30% and 20% above baseline, respectively. RESULTS Mean basal plasma ACTH level was 17·3 ± 1·7 pmol/l and rose to a peak level of 42·7 ± 4·9 pmol/l at 15 minutes Mean basal serum cortisol level was 574 ± 19 nmol/l and rose to a peak level of 814 ± 28 nmol/l at 45 minutes. ACTH and cortisol incremental changes were inversely correlated with their respective basal levels. Ninety patients (84·1%) had an ACTH and 84 patients (78·5%) had a cortisol response to desmopressin. Several clinical and demographic characteristics were not significantly different among desmopressin responders and non responders, except that basal ACTH and cortisol levels were significantly higher in desmopressin non responders (27·2 ± 8·3 pmol/l, 781 ± 86 nmol/l) than in desmopressin responders (15·4 ± 1·2 pmol/l, 535 ± 14 nmol/l). Disappearance of the ACTH and cortisol response to desmopressin after surgery occurred in 50 of 87 (57%) ACTH responders and in 57 of 81 (70·4%) cortisol responders, respectively. However, concordance between the desmopressin test and surgical outcome was not complete. Indeed, 18 patients considered in remission still showed an ACTH increase after desmopressin and, on the contrary, four patients with disappearance of the ACTH response had persistence of hypercortisolism. During follow-up monitoring, three patients, who had persistence of the ACTH response to desmopressin, relapsed 24, 38 and 54 months after surgery. CONCLUSIONS Desmopressin administration elicits a significant rise in ACTH and cortisol levels in the majority but not all patients with Cushing's disease. There is a good, but not complete, concordance between the response to the desmopressin test and the surgical outcome. Our preliminary data show that persistence of the ACTH response to desmopressin in the early postoperative period might be associated with a higher risk of late relapse.

Endocrine inactive pituitary adenomas represent about one quarter of all pituitary tumors. By immunocytochemistry, most of these tumors are positive for intact gonadotropins and/or their subunits. Clinical presentation is usually secondary to mass effect symptoms, such as visual disturbances, headache, and hypopituitarism. Differential diagnosis is usually accomplished by neuroradiologic studies, even though in selected cases positron emission tomography and/or single photon emission tomography may aid to distinguish pituitary adenomas from other endocrine inactive lesions, such as meningiomas and craniopharyngiomas. Surgical management is usually considered the first choice treatment for patients with endocrine inactive pituitary adenomas because it is very effective in ameliorating symptoms of chiasmal compression and headache. Radical removal of the tumor, however, is difficult to obtain because of the frequent invasiveness into the cavernous sinus. Radiation therapy diminishes the likelihood of tumor recurrence, especially in patients with demonstrable tumor remnants after surgery. Medical therapy with dopaminergic drugs, somatostatin analogs, or gonadotropin-releasing hormone agonists or antagonists causes mild reduction of tumor size in few patients and, therefore, seems to be of limited value in the therapeutic management of patients with endocrine inactive pituitary adenomas.

Surgery for benign neoplasm extending into the orbital roof requires immediate reconstruction to avoid complications, which include transmission of the cerebral pulse to the globe, bulbar dystopia, diplopia, and fibrosis of the oculomotor muscles. Many alloplastic materials have been employed for such reconstruction, but currently most authors agree that autologous bone graft is the best option. Using calvarial bone in adults and split ribs in children, we have operated on eight patients for fibrous dysplasia (five cases), neurofibroma (two cases), or meningioma (one case). After a median follow-up period of two years and six months, good morphology of the orbit was maintained with no ocular symptoms.

We investigated the growth fraction and cell loss fraction in a large group of patients with Cushing's disease subdivided according to tumor size. Fifty-one patients, 8 males and 43 females, aged 12 through 61 years (mean age 34.6 ± 1.5 years), were studied. Thirty-six patients had a microadenoma and the remaining 15 a macroadenoma. Immunohistochemical analysis was performed on paraffin-embedded material using a monoclonal antibody (MIB-1) directed against a proliferation-associated nuclear antigen, Ki-67, to measure the growth fraction. Apoptosis was assessed by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method, using a monoclonal antibody recognizing areas of DNA fragmentation. Ki-67 labeling index and apoptosis were counted on separate slides in at least 1000 evaluable cells. Patients with a macroadenoma had a significantly higher value of Ki-67 index (9.3 ± 2.7%) than patients with microadenoma (2.8 ± 0.5%; P versus 0.8 ± 0.3% in microadenomas). Our study shows that ACTH-secreting macroadenomas are characterized by a higher cell growth fraction than microadenomas, whereas the cell loss fraction is not different. A high proliferation rate seems to play a major role in determining the progression from small to large pituitary tumors in Cushing's disease.

The reported cases of hyperthyroidism due to a TSH-secreting pituitary adenoma have steadily increased in previous years; however, information about the results and long term outcome after pituitary surgery is scanty. Twenty-four patients with a TSH-secreting adenoma underwent pituitary surgery at our department in the last 15 years. Hypersecretion of other pituitary hormones was diagnosed in 7 patients. Three patients were euthyroid at the time of surgery because of previous ablative thyroid therapies. The success rate of surgery strictly depends on the criteria used. Normalization of elevated FT3 and FT4 levels occurred in 17 of the 21 patients with preoperative hyperthyroidism: however, only those with early postoperative undetectable TSH level (12 cases) had no recurrence of disease during follow-up and no residual tumor tissue on postoperative MRI, whereas recurrence of hyperthyroidism occurred in 3 of the 5 patients without postoperative TSH inhibition. All 3 euthyroid patients had a subtotal removal of the tumor, as judged by postoperative MRI. Surgical removal is the therapy of choice of TSH-secreting adenomas, whereas radiotherapy and medical treatment with somatostatin analogues are usually reserved to patients with incomplete tumor removal. A thorough postoperative evaluation is necessary to discriminate between complete and partial remission of disease.

Dear Editor, We report the case of a 46-year-old immunocompetent woman with a 10-month-long history of progressive exophthalmia, right palpebral ptosis, and retro-orbital pain. The patient referred also a severe left ocular maculopathy since she was 17 years old. Physical examination revealed a right exophthalmia; blood cell count and other basic laboratory investigations were within normal ranges, with the exception of a not quantifiable monoclonal component at serum electrophoresis. Magnetic resonance imaging (MRI) and computed tomography (CT) scan showed a right cavernous sinus mass with implant on the meninges associated with intrasellar and intraorbital extension and erosion of the right superior orbital fissure without parenchymal infiltration. These findings supported a neuroradiological diagnosis of meningioma. Cerebrospinal fluid examination was normal. A partial resection of the intraorbital mass was performed. The gross specimen consisted of small fragments (i.e., 0.5 cm in maximum diameter) including bone spiculae. Histopathology revealed a mucosa-associated lymphoid tissue non-Hodgkin’s lymphoma (MALT-NHL) with an extensive plasma cell differentiation arising from the dura and infiltrating the underlying bone. Lymphoid cells were mainly represented by smallto intermediate-sized elements with somewhat regular nuclei and relatively abundant clear cytoplasm, forming loose aggregates in the intertrabecular areas of bone fragments (Fig. 1a). Lymphoid cells were immunoreactive for CD20 (Fig. 1c) and negative for CD3, CD21, CD138, IgM, IgD, cyclin D1, EMA, and myeloperoxidase. A significant proportion of tumor was represented by mature-appearing plasma cells, which, in some areas, were virtually the only recognizable elements (Fig. 1b) and showed immunoreactivity for CD138 (Fig. 1d) with lambda light chain restriction (Fig. 1e, f). The postoperative period was uneventful and a complete staging workup, including blood cell count, total-body CT scan, and bone marrow biopsy, ruled out any systemic lymphomatous involvement. Helicobacter pylori infection and gastric lymphoma were excluded by multiple biopsies. The patient’s well-known long history of left ocular maculopathy prevented the adoption of radiotherapy to avoid further damage to both eyes. Accordingly, treatment with the anti-CD20 monoclonal Ann Hematol (2009) 88:599–601 DOI 10.1007/s00277-008-0638-x

Given the extensive histomorphological heterogeneity of high-grade gliomas, in terms of extent of invasiveness, angiogenesis, and necrosis and the poor prognosis for patients despite the advancements made in therapeutic management. The identification of genes associated with these phenotypes will permit a better definition of glioma heterogeneity, which may ultimately lead to better treatment strategies. CXCR4, a cell surface chemokine receptor, is implicated in the growth, invasion, angiogenesis and metastasis in a wide range of malignant tumors, including gliomas. It is overexpressed in glioma cells according to tumor grade and in glioma tumor initiating cells. There have been various reports suggesting that CXCR4 is required for tumor proliferation, invasion, angiogenesis, and modulation of the immune response. It may also serve as a prognostic factor in characterizing subsets of glioblastoma multiforme, as patients with CXCR4-positive gliomas seem to have poorer prognosis after surgery. Aim of this review was to analyze the current literature on biological effects of CXCR4 activity and its role in glioma pathogenesis. A better understanding of CXCR4 pathway in glioma will lead to further investigation of CXCR4 as a novel putative therapeutic target.

Background and Objectives Few simulation models are available that provide neurosurgical trainees with the challenge of distorted skull base anatomy despite increasing importance in the acquisition of safe microsurgical and endoscopic techniques. We have previously reported a unique training model for skull base neurosurgery where a polymer is injected into a cadaveric head where it solidifies to mimic a skull base tumor for resection. This model, however, required injection of the polymer under direct surgical vision via a complicated alternative approach to that being studied, prohibiting its uptake in many neurosurgical laboratories. Conclusion We report our updated skull base tumor model that is contrast-enhanced and may be easily and reliably injected under fluoroscopic guidance. We have identified a map of burr holes and injection corridors available to place tumor at various intracranial sites. Additionally, the updated tumor model allows for the creation of mass effect, and we detail the variation of polymer preparation to mimic different tumor properties. These advancements will increase the practicality of the tumor model and ideally influence neurosurgical standards of training. © Georg Thieme Verlag KG.

"Background: Tumours of the clivus are exceptionally rare, representing a diagnostic and a therapeutic challenge. Clival solitary plasmocytomas have been described only as single case reports or included in small clinical series with other intracranial location. Methods: Authors report clinical, radiological, and survival data of four patients, who underwent surgery for clival plasmocytomas between 1989 and 2012 in a single centre. Current knowledge about solitary plasmocytomas of the clivus are reviewed. Results: Follow-up time was 54 months (range: 9-165). Mean age of patient was 57 years, no gender predilection was observed. Main symptoms were headache (75 %) and double vision (75 %), due to third or sixth cranial nerve palsy. Mean time to diagnosis was 8.2 months. All patients underwent surgery as primary treatment, through either a transsphenoidal (75 %) or a transmaxillary approach (25 %). In all cases adjuvant conventional radiotherapy was performed with a median delivered dose of 45 Gy. Only one case of progression into multiple myeloma was observed 13 months after surgery, and the patient died 9 months later. No other recurrences or progression were observed. Mean overall survival and progression free survival time were, respectively, 54 and 51.7 months. Conclusions: Although extremely rare, clival plasmocytomas have to be considered in the differential diagnosis of a solitary clival lesion. Biological and clinical features of these tumours strongly differ from those of similar lesions in other part of the body. Early diagnosis, extensive tumour removal, opportune indication of adjuvant treatment with radiotherapy and chemotherapy are the keys to manage these cases. © 2013 Springer-Verlag Wien."

ObjectiveFew data are available on the surgical results in patients with incidentally discovered nonfunctioning pituitary adenoma (NFPA). We investigated the efficacy and safety of surgery in patients with incidentally discovered NFPA.DesignRetrospective analysis of prospectively recorded outcomes.MethodsFrom 1990 to 2011, of 804 consecutive patients undergoing surgery for NFPA, 212 cases had an incidentally discovered tumor (26.4%). Among them, 117 patients were asymptomatic, while 95 had some visual and/or hormonal deficit. The main outcome of the study was to evaluate the frequency of radical resection as judged on the first postoperative neuroimaging study and detection of recurring disease during long-term follow-up.ResultsPostoperative residual tumor was detected in 8.9% of patients with asymptomatic incidentalomas as compared with 31.2% of patients with symptomatic incidentalomas (PPPConclusionOur study shows for the first time that surgically treated patients with asymptomatic NFPA have a better early and long-term outcome that is independent from all the other demographic, clinical, and morphologic characteristics of the patients.

"A nonchordomatous solitary lesion of the clival bone is an exceptionally rare pathological entity, which represents a diagnostic and a therapeutic challenge. Many diseases with extremely different biological behavior, and requiring a dedicated treatment strategy, may result in similar clinical patterns. The approach to a correct differential diagnosis has to consider the specific epidemiological, radiological, and histopathological characteristics of each pathology to minimize the diagnostic bias and to allow the planning of the best treatment strategy. Because of the rarity of these diseases, a systematical review of nonchordomatous lesions of the clival bone still lack in the literature. The purposes of this study are to provide an overview of the epidemiological, clinical, radiological, and histopathological characteristics of nonchordomatous clival lesions, with particular emphasis on diagnostic and therapeutic strategies and related clinical outcome. © 2013 Springer-Verlag Berlin Heidelberg.. . "