Efficacy of radiotherapy and stereotactic radiosurgery as adjuvant or salvage treatment in atypical and anaplastic (WHO grade II and III) meningiomas: a systematic review and meta-analysis.

The role of radiotherapy (RT) and stereotactic radiosurgery (SRS) as adjuvant or salvage treatment in high-grade meningiomas (HGM) is still debated. Despite advances in modern neuro-oncology, HGM (WHO grade II and III) remains refractory to multimodal therapies. Published reports present aggregated data and are extremely varied in population size, exclusion criteria, selection bias, and inclusion of mixed histologic grades, making it extremely difficult to draw conclusions when taken individually. This current work aims to gather the existing evidence on RT and SRS as adjuvants following surgery or salvage treatment at recurrence after multimodality therapy failure and to conduct a systematic comparison between these two modalities. An extensive systematic literature review and meta-analysis were performed. A total of 42 papers were eligible for final analysis (RT n = 27; SRS n = 15) after searching MEDLINE via PubMed, Web-of-science, Cochrane Wiley, and Embase databases. Adjuvant regimens were addressed in 37 papers (RT n = 26; SRS n = 11); salvage regimens were described in 5 articles (RT n = 1; SRS n = 4). The primary outcomes of the study were the overall recurrence rate and mortality. Other actuarial rates (local and distant control, OS, PFS, and complications) were retrieved and analyzed as secondary outcomes. A total of 2853 patients harboring 3077 HGM were included. The majority were grade II (87%) with a mean pre-radiation volume of 8.7 cc. Adjuvant regimen: 2742 patients (76.4% RT; 23.6% SRS) with an overall grade II/III rate of 6.6/1. Lesions treated adjSRS were more frequently grade III (17 vs 12%, p < 0.001), and received subtotal resection (57 vs 27%, p = 0.001) compared to the RT cohort. AdjSRS cohort had a significantly shorter mean follow-up than adjRT (36.7 vs 50.3 months, p = 0.01). The overall recurrence rate was 38% in adjRT vs 25% in adjSRS (p = 0.01), while mortality did not differ between the groups (20% vs 23%, respectively; p = 0.80). The median time to recurrence was 1.5 times longer in the RT group (p = 0.30). Five-year local control was 55% in adjRT and 26% in adjSRS (p = 0.01), while 5-year OS was 73% and 78% (p = 0.62), and 5-year PFS was 62% and 40% in adjRT and adjSRS (p = 0.008). No difference in the incidence of complications (24% vs 14%, p = 0.53). Salvage regimen: 110 patients (37.3% RT; 62.7% SRS) with a grade II/III rate of 8.6/1. The recurrence rate was 46% in salRT vs 24% in salSRS (p = 0.39), time to recurrence was 1.8 times longer in the salRT group (35 vs 18.5 months, p = 0.74). Mortality was slightly yet not significantly higher in salRT (34% vs 12%, p = 0.54). Data on local and distant control were only available for salSRS. The 5-year OS was 49% and 83% (p = 0.90), and the 5-year PFS was 39% and 50% in salRT and salSRS (p = 0.66), respectively. High-grade meningiomas (WHO grade II and III) receiving adjuvant RT showed a higher overall recurrence rate than meningiomas receiving adjuvant SRS. The adjRT cohort, however, achieved higher 5-year LC and PFS rates, thus suggesting a potentially longer time to recurrence compared to adjSRS patients, who, meanwhile, experienced a significantly shorter follow-up. This result must also consider the higher number of grade III lesions and the smaller extent of resection achieved in the adjSRS group. Overall mortality did not differ between the two groups. No differences in outcome measures were observed in salvage regimens.

Benign and Malignant Tumors of the Pituitary Gland.

Pituitary gland tumors represent approximately 10-15% of all brain tumors and the most common neoplasms of the sellar region. Among them, pituitary adenomas are the widespread accounting for more than 80%. Recently, the fourth edition of the World Health Organization (WHO) 2017 classified pituitary tumors focusing on histopathologic and molecular genetics features and introduced new entities like pituitary blastoma. Most of pituitary gland neoplasms occur sporadically, whereas 5% are related to familial syndromes. They present with several clinical manifestations including signs and symptoms related to excessive hormone secretion by the tumor, signs of hormone deficits by the normal pituitary gland and others commonly secondary to mass effects, and compression of nearby structures such as the optic chiasm; headache and visual disturbance are the most frequent mass effect symptoms. Some tumors, however, are detected as an incidental finding on magnetic resonance imaging (MRI) or computed tomography (CT) scans performed for some other reasons. A correct evaluation involves the assessment of hypothalamic-pituitary hormonal function and an ophthalmological examination once a pituitary lesion is encountered. Surgery, more specifically transsphenoidal approach, represents the primary treatment chosen for the majority of pituitary tumors (except for prolactinomas where medical treatment is indicated) allowing for pathologic analysis and complete or partial tumor removal. On the contrary, to date, craniotomy is rarely performed. Sometimes, due to the proximity of critical structures and to tumor's location and characteristics, a successful surgical procedure may often not be achievable due to the high risks related to the procedure itself. Therefore, the treatment of pituitary tumors commonly requires a multimodal approach, including surgery, radiosurgery, radiation therapy, and medical therapy. Aggressive pituitary tumors or carcinomas are associated with poor prognosis due to limited therapeutic options. Furthermore, they tend to recur quickly after initial surgical treatment or present metastasis, may be unresponsive to therapy, and are difficult to manage. In this chapter, we provide an overview of the most common pituitary gland tumors focusing on epidemiology, new pathological features, diagnosis, available treatment, and prognosis.

Primary sellar melanocytoma: report of two cases treated at the same institution and their long-term outcome.

Sellar melanocytomas represent a small subgroup of primary melanocytic tumors arising from leptomeningeal melanocytes. They are benign, slow-growing tumors with a high risk of recurrence. We report two cases of sellar melanocytoma treated at the same institute. A 35-year-old woman presented with amenorrhea and an intrasellar mass with suprasellar extension simulating a hemorrhagic pituitary adenoma. The second case is a 51-year-old man with progressive visual loss and a recurrence of primary sellar and suprasellar melanocytoma. The first patient underwent gross total resection and the second patient underwent subtotal resection. Neither of them was treated with postoperative adjuvant therapies. The second patient had tumor regrowth 75 months after surgery; he therefore underwent gamma knife radiosurgery. Both patients are alive and well at the last follow-up (140 and 93 months, respectively).

A Novel Assay in Whole Blood Demonstrates Restoration of Mitochondrial Activity in Phagocytes After Successful HSCT in Hyperinflamed X-Linked Chronic Granulomatous Disease.

X-linked chronic granulomatous disease is a rare disease caused by mutations in the CYBB gene. While more extensive knowledge is available on genetics, pathogenesis, and possible therapeutic options, mitochondrial activity and its implications on patient monitoring are still not well-characterized. We have developed a novel protocol to study mitochondrial activity on whole blood of XCGD patients before and after transplantation, as well as on XCGD carriers. Here we present results of these analyses and of the restoration of mitochondrial activity in hyperinflamed X-linked Chronic Granulomatous Disease after hematopoietic stem cell transplantation. Moreover, we show a strong direct correlation between mitochondrial activity, chimerism, and DHR monitored before and after transplantation and in XCGD carriers. In conclusion, based on these findings, we suggest testing this new ready-to-use marker to better characterize patients before and after treatment and to investigate disease expression in carriers.

Alterations of brain structural MRI are associated with outcome of surgical treatment in trigeminal neuralgia.

BACKGROUND AND PURPOSE: To assess magnetic resonance imaging (MRI) alterations occurring in patients with trigeminal neuralgia (TN) and to explore the predictive ability of MRI for initial surgical outcome and long-term pain relief/recurrence after Gamma Knife radiosurgery (GKS). METHODS: Thirty patients with idiopathic or classic TN, who underwent GKS and were followed for at least 24 months, were retrospectively included. Pre-treatment structural MRI and pre- and serial, postoperative clinical features were investigated. Fifteen age- and sex-matched healthy controls were also enrolled. Cortical thickness and gray matter (GM) volumes were assessed in TN patients relative to controls, as well as between patient subgroups according to treatment outcomes (initial responders/non-responders, patients with pain recurrence/long-lasting pain relief at the last follow-up). Clinical and MRI predictors of treatment outcomes were explored. RESULTS: Cortical thinning of temporal, prefrontal, cingulate, somatosensory and occipital areas bilaterally was found in TN patients relative to controls. No cortical thickness and GM volume differences were observed when TN initial responders and non-responders were compared. Patients who experienced TN recurrence after initial pain relief were characterized by thicker parahippocampal and temporal cortices bilaterally and greater volume of right amygdala and hippocampus compared to patients with long-lasting pain relief. In TN patients, disease duration and baseline cortical thinning of right parahippocampal, left fusiform and middle temporal cortices were associated with poor outcome after GKS at the last follow-up (R2 =0.57, p<0.001). CONCLUSION: The study provides novel insights into structural brain alterations of TN patients, which might contribute to disease development and pain maintenance.

Comparison between extended transsphenoidal and transcranial surgery for craniopharyngioma: focus on hypothalamic function and obesity.

PURPOSE: Patients suffering from craniopharyngiomas currently have good survival rates, but long-term sequelae, such as development of obesity, worsen their quality of life. Optimal treatment is still controversial and changed during the decades, becoming less aggressive. Transcranial (TC) surgery was the first approach to be used, followed by extended transsphenoidal (eTNS) access. This study aims to compare the two approaches in terms of risk of hypothalamic damage leading to obesity. METHODS: This is a monocentric retrospective analysis of post-puberal patients treated for primary craniopharyngioma. Postoperative obesity and percentual postsurgical BMI variation were considered proxy for hypothalamic function and used to fit regression models with basal BMI, type of surgery, tumor volume and hypothalamic involvement (anterior vs. anteroposterior). RESULTS: No difference in radicality was observed between the two approaches; eTNS was more effective in ameliorating visual function but was significantly associated with CSF leaks. The TC approach was associated with a higher incidence of diabetes insipidus. Regression analysis showed only tumor volume and basal BMI resulted as independent predictors for both postoperative obesity (respectively, OR 1.15, P = 0.041, and OR 1.57, P < 0.001) and percentual BMI variation (respectively, + 0.92%, P = 0.005, and - 1.49%, P = 0.001). CONCLUSIONS: Larger lesions portend a higher risk to develop postoperative obesity, independently of hypothalamic involvement. Interestingly, basal BMI is independent of lesional volume and is associated with postoperative obesity, but lesser postoperative BMI variation. The surgical approach does not influence the obesity risk. However, eTNS proves valid in managing large tumors with important hypothalamic invasion.

The open sella technique for surgical treatment of pituitary macroadenomas: Safety and efficacy in a large clinical series.

PURPOSE: To analyse the efficacy and safety of the transsphenoidal microsurgical approach with open sella technique (OST) for the treatment of pituitary adenoma (PA) with suprasellar extension. METHODS: We retrospectively reviewed 2305 consecutive patients with PA who underwent their first surgery through the transsphenoidal microsurgical approach at our department between 1990 and 2018. Focusing on tumours with suprasellar extension, in particular, grade B, C and D adenomas according to Wilson-Hardy's classification, 376 patients who received the OST surgery were identified. Outcomes and complications were evaluated and compared with those obtained in patients who underwent a standard transsphenoidal approach (TSM). RESULTS: Two-hundred and sixty-four of 376 patients (70.2%) were found to be suffering from a non-functioning pituitary adenoma, whereas 112 of 376 patients (29.8%) from a hormone-secreting PA. The mean craniocaudal diameter of the tumor was 30.6 ± 0.3 mm (range, 21-75 mm) and 151 patients (40.1%) had a cavernous sinus invasion too. An overall surgical remission rate of 50.3% was achieved in the OST group, whereas the recurrence rate was 10.5%. Patients were followed for a mean period of 68 ± 1.4 months (range, 6-96 months). Less postoperative intrasellar haemorrhages have been recorded in the OST group than the TSM one (1.1% vs. 4.6%, p = 0.02). CONCLUSIONS: In experienced hands, OST represents an effective and safe treatment strategy for PA with suprasellar extension.

Microsurgical endoportal MRI/US-navigated approach for the resection of large intraventricular tumours: a 20-consecutive patients case series.

OBJECTIVES: Deep lesions located in lateral and third ventricles can be accessed thorough interhemispheric transcallosal or transcortical trans-ventricular approaches. Traditional brain retractors are made by 'non-cerebral engineered' spatulas, which do not equally distribute pressure on surrounding structures damaging brain. In this paper, we present a series of 20 intraventricular tumours resected through a MRI/US-navigated microscopic transcortical endoportal approach. PATIENTS AND METHODS: Between January 2014 and December 2017, 20 patients underwent US-MRI neuronavigated (Esaote®, Genova, Italy) transcortical endoportal (Vycor® Viewsite Brain Access System TC Model, Vycor® Medical Inc., Boca Raton, FL) surgery for intraventricular deep-seated lesions with the intent to reach maximal safe resection. RESULTS: Gross total removal was achieved in 14 patients (70%). The only prognostic factor that resulted in statistical significance related to surgical radicality from multivariate analysis was white matter infiltration (p = 0.043), regardless of other tumour (dimensions, origin and location inside ventricular system, histopathology) and patient (age, gender, clinical presentation) characteristics. The mean duration of surgery was 225.9 min (± 59). Neither critical events, nor major bleedings, nor intraoperative deaths occurred during surgery. One case of postoperative CSF infection (5%) was registered. Six patients (30%) required permanent CSF drainage system (Ommaya reservoir, VP shunt) in the postoperative period. The mean Functional Independence Measure (FIM) score at last follow-up was 105 (range: 65-124). CONCLUSIONS: Transcortical transventricular endoportal surgery seems to be a valuable alternative to transcallosal surgery, although further prospective multicentre studies with larger number of patients, evaluation of pre- and post-operative neuropsychological outcomes and achievement of postoperative DTI and f-MRI are needed to confirm our results.

Pretreatment with somatostatin analogs does not affect the anesthesiologic management of patients with acromegaly.

PURPOSE: Acromegaly may be associated with an increased risk of complex intraoperative management and anesthetic complications. No study addressed whether pretreatment with somatostatin receptor ligands (SRLs) affects anesthesiologic management. METHODS: We studied 211 consecutive acromegalic patients who had a recorded intraoperative computerized anesthetic record (ICAR) available for analysis. Ninety-six (45.5%) patients were SRL-pretreated while 115 patients were treatment naïve. RESULTS: Treatment with SRLs reduced mean basal growth hormone level from 23.8 ± 4.2 to 5.9 ± 1.3 µg/L. Normalization of insulin-like growth factor-1 was achieved in 26 patients (27.1%). The frequency of comorbidities at surgery was similar in the two groups. Five patients with difficult intubation were naïve (4.3%) as compared with 5 SRL-pretreated patients (5.2%; P = 1.0). ICAR registration did not show any significant change of intraoperative vital parameters in the two groups of patients as well as in the intraoperative utilization of drugs. Total duration of anesthesia and surgery were similar in the two groups. Four patients with an intraoperative adverse event were naïve (3.5%) as compared with 4 SRL-pretreated patients (4.2%; P = 1.00). Remission of disease occurred in 83 of 114 naïve patients (72.8%) and in 57 of 93 SRL-pretreated patients (61.3%; P = 0.11). CONCLUSIONS: SRL-pretreatment of patients with acromegaly had no significant impact on intraoperative anesthesiologic management. Despite a better Cormack-Lehane score in SRL-pretreated than in naïve patients, the rate of difficult intubation was similar in both groups. SRL-pretreatment did not affect the rate of surgical remission or complications as well.

Sublabial transsphenoidal microsurgical technique to treat congenital transsphenoidal encephalocele: a technical note.

Encephalocele is a rare malformation consisting in herniation of cranial contents through a cranial defect. A transsphenoidal location is uncommon, representing 5% of all basal encephaloceles. The surgical treatment of transsphenoidal encephaloceles is challenging. An optimal approach has not yet been determined, and it varies according to the surgical experience. We report the surgical management of a transsphenoidal encephalocele. The encephalocele and the sellar defect were repaired through a sublabial transsphenoidal microsurgical approach (TSM). Preoperative magnetic resonance imaging (MRI) and computed tomography (CT) scans were crucial for surgical planning. The sublabial transsphenoidal microsurgical approach offered a good and complete exposure of both the sac and the bone defect. Therefore, the congenital defect was successfully repaired with complete resolution of the encephalocele without any surgical or medical complications. Postoperative CT scan and MRI showed the restoration of the bone defect and the recovery of a normal anatomy with herniated structures pushed back into the sella. The described sublabial transsphenoidal microsurgical approach represents a minimally invasive, safe, and effective treatment strategy for transsphenoidal encephalocele.

Bone resorption in autologous cryopreserved cranioplasty: quantitative evaluation, semiquantitative score and clinical significance.

BACKGROUND: Changes after reimplantation of the autologous bone have been largely described. However, the rate and the extent of resorption in cranial grafts have not been clearly defined. Aim of our study is to evaluate the bone flap resorption (BFR) after cryopreservation. METHODS: We retrospectively reviewed 27 patients, aged 18 years or older, subjected to cranioplasty (CP) adopting autologous cryopreserved flap. The BFR was derived from the percentage of decrease in flap volume (BFR%), comparing the first post-operative computed tomography (CT) and the last one available (performed at least 1 year after surgery). We also proposed a semiquantitative scoring system, based on CT, to define a clinically workable BFR classification. RESULTS: After a mean ± SE follow-up of 32.5 ± 2.4 months, the bone flap volume decreased significantly (p < 0.0001). The mean BFR% was 31.7 ± 3.8% and correlated with CT-score (p < 0.001). Three BFR classes were described: mild (14.8% of cases) consisting in minimal bone remodelling, CT-score ≤ 6, mean BFR% = 3.5 ± 0.7%; moderate (51.9% of cases) corresponding to satisfactory cerebral protection, CT-score < 13, mean BFR% = 25.6 ± 2.2%; severe (33.3% of cases) consisting in loss of cerebral protection, CT-score ≥ 13, mean BFR% = 54.2 ± 3.9%. Females had higher BFR% than males (p = 0.022). BFR classes and new reconstructive surgery were not related (p = 0.58). CONCLUSIONS: BFR was moderate or severe in 85.2% of re-implanted cryopreserved flaps. The proposed CT-score is an easy and reproducible tool to define resorption extent.

Hemorrhagic burden in poor-grade aneurysmal subarachnoid hemorrhage: a volumetric analysis of different bleeding distributions.

BACKGROUND: Volumetric assessment of aneurysmal bleeding has been evaluated in few studies and emerged as a promising outcome predictor. There is a lack of studies evaluating its impact in the poor-grade population. METHODS: Retrospective review of 63 consecutive poor-grade aneurysmal subarachnoid hemorrhage (aSAH) patients, defined as grade IV and V according to the World Federation of Neurological Surgeons (WFNS) classifications. Global intracranial bleeding volume was calculated with its subarachnoid, intracerebral (ICH), and intraventricular (IVH) portions by means of analytical software. Univariate and multivariate analyses were performed in order to identify independent predictors of outcome. Good outcome was defined as modified Rankin Scale (mRS) 0-2 and mortality as mRS 6. The cutoff values of bleeding volumes were derived by receiver operating curve (ROC) analysis. RESULTS: Mean follow-up was of 12.5 (± 1.5) months. Thirty (47.7%) patients achieved good outcome, whereas 19 (30.2) patients out of 63 died. Global intracranial bleeding resulted as an independent predictor of good outcome (cutoff 24 mL). Furthermore, ICH relative percentage of global volume (10% of total) and pure SAH (64% of total) emerged respectively as independent predictors of worsened and improved outcome. Global bleeding volume (cutoff 51 mL) along with global cerebral edema showed to independently predict mortality in the examined poor-grade aSAH population. CONCLUSIONS: Volumetric assessment of aneurysmal bleeding has the potential for identifying cutoff values that independently predict outcome. Further insights into the relative importance of different bleeding volumes may be implicated in better tailoring the management of this dismal aSAH population.

Treatment of empty sella associated with visual impairment: a systematic review of chiasmapexy techniques.

PURPOSE: Chiasmapexy is a poorly described surgical procedure adopted to correct the downward displacement of suprasellar visual system (SVS) into an empty sella (ES) causing visual worsening. The aim of our study is to define the indications for extradural and intradural chiasmapexy. METHODS: A systematic literature review has been performed on MEDLINE database (US National Library of Medicine), including only articles that depicted cases of surgically treated patients affected by ES and progressive delayed visual worsening. Moreover, we have reported three cases of secondary ES syndrome (SESS) with visual worsening treated in our Department with transsphenoidal (TS) microsurgical intradural approach. Finally, we have compared the results of extradural and intradural chiasmapexy described in literature. RESULTS: The etiology of visual impairment is different in primary and secondary ESS. In primary ESS (PESS) the only predisposing factor is a dehiscence of diaphragma sellae, and the anatomical distortion caused by displacement of optic chiasm or traction of pituitary stalk and infundibulum may determine a direct injury of neural fibers and ischemic damage of SVS. In PESS the mechanical elevation of SVS performed through extradural approach is sufficient to resolve the main pathologic mechanism. In SESS, arachnoidal adhesions play an important role in addition to downward herniation of SVS. Consequently, the surgical technique should provide elevation of SVS combined to intradural release of scar tissue and arachnoidal adhesions. In treatment of SESS, the intradural approaches result to be more effective, guaranteeing the best visual outcomes with the lowest complications rates. CONCLUSIONS: The intradural chiasmapexy is indicated in treatment of SESS, instead the extradural approaches are suggested for surgical management of PESS.

Single fraction and multisession Gamma Knife radiosurgery for craniopharyngioma.

PURPOSE: The optimal management of residual or recurring craniopharyngioma is still a matter of debate even though adjuvant radiation therapy plays a crucial role. Aim of our study is to report the results of single fraction or multisession Gamma Knife radiosurgery (GKRS) in patients with craniopharyngioma. METHODS: We included 50 consecutive patients treated from 1994 to 2016. All patients had at least one post GKRS magnetic resonance imaging reviewed at our center. Vital status of all patients was assessed at the end of 2016. RESULTS: There were 29 males (58.0%) and 21 females (42.0%). Mean age was 41.5 ± 2.8 year. Single session GKRS was delivered in 29 patients (58.0%). The mean tumor volume was 2.15 ± 0.3 cm3 and the mean prescription dose to the tumor margin was 14.3 ± 0.3 Gy. During a mean follow-up of 74.6 ± 8.4 months, seven patients (14.0%) had recurrence of disease. The 5- and 10-year recurrence-free survivals were 90.3% (95% CI, 81.0-99.6%) and 78.4% (95% CI, 59.9-96.9%), respectively. Multisession GKRS was not less effective than single fraction GKRS. Eighteen of the 28 patients (64.3%) had a tumor volume decrease of at least 10%. No serious side effects occurred after GKRS treatment, except for one case of mild visual worsening. CONCLUSIONS: GKRS was effective for controlling the growth of residual or recurrent craniopharyngioma. Serious side effects were uncommon. Multisession GKRS seems a very promising tool to allow performing GKRS even in patients with large residual or recurrent craniopharyngioma.

Suprasellar granular cell tumor of the neurohypophysis: surgical outcome of a very rare tumor.

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.

Efficacy and safety of radiosurgery in acromegaly.

Stereotactic radiosurgery (SRS) more and more frequently plays a crucial role in the treatment of acromegaly. We provide a systematic review of the literature and meta-analysis, according to PRISMA, on SRS for the management of growth hormone (GH)-secreting pituitary adenomas, including several radiosurgical techniques, with the aim of describing efficacy and safety of this treatment. A weighted random effects model was used to calculate pooled outcome estimates. From 346 abstract reviews, 27 retrospective studies were included. Despite the variability in hormonal remission criteria and the heterogeneity between treatment guidelines among included studies, most of them reported an endocrine remission rate between 40% and 60%. Random effects meta-analysis for overall endocrine remission and 5-year probability of remission estimate after SRS were 46% (95% CI: 39-53%) and of 48% (95% CI: 38-57%), respectively. Random effects meta-analysis for new hypopituitarism estimate after SRS was 23% (95% CI: 17-29%). Furthermore, incidence of radiation induced optic neuropathy after SRS ranged between 0% and 6% This meta-analysis confirms and quantifies safety and effectiveness of SRS to achieve endocrine remission after surgical management in acromegaly.

Single Versus Fractionated Gamma Knife Radiosurgery for Nonfunctioning Pituitary Adenomas Close to the Optic Pathway: A Multicenter Propensity Score Matched Study.

BACKGROUND AND OBJECTIVES: Gamma Knife radiosurgery (GKRS), typically administered in a single session (S-GKRS), is an effective treatment for nonfunctioning pituitary adenoma (NFPA). For lesions close to the optic pathway, the use of hypofractionated radiosurgery is growing. This study seeks to compare the results of S-GKRS vs fractionated-GKRS (F-GKRS) for NFPAs adjacent to the optic pathway. METHODS: Two cohorts of patients with residual or recurrent NFPAs in contact to the optic pathway were retrospectively included in this study: (1) a group of patients who underwent a 3-day course of F-GKRS in Europe and (2) a group of patients treated with S-GKRS in the United States. A propensity score matching (ratio 1:1) was carried out to obtain and compare 2 homogeneous groups of patients with NFPA. RESULTS: A total of 84 patients were included for analysis (42 in the S-GKRS cohort and 42 in the F-GKRS group). The 2 cohorts did not differ for age, sex, number of previous surgical procedure, tumor volume, and follow-up. The mean follow-up was 60.2 ± 37.0 months and 62.4 ± 37.4 months for F-GKRS and S-GKRS cohort, respectively ( P = .38). The overall tumor control at last follow-up was achieved in 95.2% and 92.9% of patients in F-GKRS and S-GKRS, respectively ( P = .64). The 1-year, 3-year, 5-year, and 7-year progression-free survival rate after F-GKRS was 100%, 97.1%, 97.1%, and 91%, respectively. In the S-GKRS sample, progression-free survival rates were 100%, 100%, 92.5%, and 92.5% at 1, 3, 5, and 7 years after treatment, respectively. Two patients (4.7%) from the F-GKRS cohort and 2 (4.7%) from the S-GKRS cohort sustained visual worsening after radiosurgery ( P = 1.0). CONCLUSION: In the management of NFPAs adjacent to the optic pathway both F-GKRS and S-GKRS had comparable outcomes and risks at 7 years. Future prospective studies including larger cohorts with longer follow-up are needed to confirm our results.

Longitudinal brain functional connectivity changes induced by neurosurgical thalamotomy for tremor in Parkinson's disease: a preliminary study.

The hypothesis that the effectiveness of neurosurgical procedures in Parkinson's disease (PD) would be related to connectivity dysfunctions between the site of the stimulation and other brain regions is growing. This study aimed to assess resting-state functional connectivity between thalamic ventral intermediate nucleus (Vim) and the rest of the brain before and after thalamotomy in PD. A 76-year-old right-handed woman with refractory tremor-dominant PD was selected as a candidate for left Vim radiosurgery thalamotomy. Clinical and motion sensor evaluation and brain resting-state functional MRI (rs-fMRI) were carried out before treatment and 3, 6, and 12 months later. Targeted Vim was selected as region of interest and a seed-based rs-fMRI analysis was performed in the patient and ten age- and sex-matched controls at baseline and over time. Furthermore, a correlation analysis between functional connectivity and tremor data was carried out. Both clinical and motion sensor measurements showed a progressive tremor improvement over time on right side after radiosurgery. In the patient, seed-based analysis showed a significantly increased functional connectivity between targeted Vim and ipsilateral visual areas relative to controls before treatment. Over 1 year, a normalization of aberrant pre-therapeutic functional connectivity between Vim and visual areas was obtained. At correlation analysis, the reduction of tremor metrics over time, assessed by clinical evaluation and wearable motion sensors, was related to the reduction of the left Vim-left visual cortex functional connectivity. Our findings support the evidence that fMRI was able to detect targeted Vim connectivity and its changes over time after thalamotomy.

Prognostic factors of visual field improvement after trans-sphenoidal approach for pituitary macroadenomas: review of the literature and analysis by quantitative method.

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.

Role of radiosurgery in the treatment of Cushing's disease.

Radiotherapy is a useful adjuvant treatment for patients with Cushing's disease that is not cured by surgery. In particular, Gamma Knife radiosurgery (GKRS) has been increasingly used worldwide as the preferred radiation technique in patients with persistent or recurrent Cushing's disease. The most widely accepted criterion for hormonal remission after GKRS is normalization of urinary free cortisol (UFC) levels. When a clear biological target is not identified, irradiation of the whole pituitary gland can be considered. The 5-year probability of remission is 65%-75%. Normalization of hypercortisolism usually occurs within 3 years from GKRS treatment and control of tumor growth is optimal, approaching more than 90%. No clear predictor of a favorable outcome has emerged up to now, except for the experience of the treating team. In the largest series, development of partial or complete hypopituitarism occurred between 15% and 36%. Severe side effects of GKRS, such as optic neuropathy and oculomotor palsy, are uncommon but have been documented in patients previously exposed to radiation. Recurrence of disease has been reported in as high as 16%-18% of the patients who achieved normalization of UFC levels in the two largest series, whereas smaller series did not describe late failure of GKRS. The reason for this discrepancy is unclear, as is the relationship between hormonal and tumoral recurrence. Another unresolved issue is whether treatment with adrenal blocking drugs can jeopardize the results of GKRS. GKRS is an effective second-line treatment in patients with Cushing's disease not cured by surgery. Hypopituitarism is the most frequent side effect of GKRS, whereas severe neurologic complications are uncommon in radiation-naïve patients.