Comparison Between Ventricular and Spinal Infusion Tests in Suspected Normal Pressure Hydrocephalus.

Idiopathic normal pressure hydrocephalus (iNPH) is an often-overlooked or misdiagnosed brain disorder characterized by overt ventriculomegaly and associated with gait disturbances, cognitive impairment, and urinary incontinence. If correctly diagnosed, it is considered the only form of dementia treatable with surgery, namely through a ventriculoperitoneal or ventriculoatrial shunt with programmable valves.Among the 856 spinal and ventricular infusion tests performed from 2001 to 2017 at our institution, we analyzed 106 cases selected for suspected normotensive hydrocephalus. In all cases, Intracranial Elastance Index (IEI) and outflow resistance (Rout) values were calculated: 52 of these patients underwent Spinal Katzman Test (SKT), and the remaining 54 underwent an intraventricular infusion test (IVKT). Of the 40 patients in the SKT group with pathological elastance (71%), 17 also had a Rout >12 mmHg and 23 a Rout <12 mmHg. Of the 50 patients in the IVKT group with pathological elastance (92%), 38 also had a Rout >12 mmHg and 12 a Rout <12 mmHg.IVKT and SKT to date represent two useful tools in the diagnosis of normal pressure hydrocephalus. Despite being more invasive, IVKT, including both the intracranial elastance index (IEI) and Rout analysis, could be considered more reliable than SKT and therefore could be reserved for the most controversial cases.

Intraventricular infusion test accuracy in predicting short- and long-term outcome of iNPH patients: a 10-year update of a three-decade experience at a single institution.

OBJECTIVE: In a previous work, we found that an Intracranial Elastance Index (IEI) ≥0.3 at ventricular infusion test had a high accuracy in predicting shunt response at 6 and 12 months in idiopathic normal pressure hydrocephalus (iNPH). The aim of this study was to verify the accuracy of IEI to predict response to shunt at both short- and long-term follow-up. METHODS: Retrospective evaluation of 64 patients undergoing ventriculo-peritoneal shunting for iNPH between 2006 and 2015 based on a positive ventricular infusion test (IEI≥0.3). Patients were classified according to Krauss scale and mRS preoperatively, at 1-year and at last follow-up. An improvement of at least one point at Krauss score or at mRS was considered as a good outcome; unchanged or worsened patients were grouped as poor outcome. RESULTS: Mean follow-up was 6.6 years. Improvement at Krauss scale was seen in 62.5% and 64.3% of patients at 1-year and last follow-up, respectively. Patients in good functional status (mRS≤2) increased from 25 in the preoperative period to 57% at both 1-year and last follow-up. IEI was significantly associated with Krauss (p=0.041) and mRS (p=0.036) outcome at last follow-up. Patients with worse preoperative Krauss and mRS had higher chance to improve but higher overall scores after treatment. At ROC curves, IEI showed a good long-term prediction of change in mRS from first year to last follow-up. CONCLUSIONS: IEI≥0.3 predicts outcomes at both short- and long-term, with more than 50% of patients being able to look after themselves after 6 years from treatment.

Usefulness of Brain Positron Emission Tomography with Different Tracers in the Evaluation of Patients with Idiopathic Normal Pressure Hydrocephalous.

Idiopathic normal pressure hydrocephalus (iNPH) is the only form of dementia that can be cured by surgery. Its diagnosis relies on clinical and radiological criteria. Identifying patients who can benefit from surgery is challenging, as other neurological diseases can be concomitant or mimic iNPH. We performed a systematic review on the role of positron emission tomography (PET) in iNPH. We retrieved 35 papers evaluating four main functional aspects with different PET radiotracers: (1) PET with amyloid tracers, revealing Alzheimer's disease (AD) pathology in 20-57% of suspected iNPH patients, could be useful in predictions of surgical outcome. (2) PET with radiolabeled water as perfusion tracer showed a global decreased cerebral blood flow (CBF) and regional reduction of CBF in basal ganglia in iNPH; preoperative perfusion parameters could predict surgical outcome. (3) PET with 2-Deoxy-2-[18F]fluoroglucose ([18F]FDG ) showed a global reduction of glucose metabolism without a specific cortical pattern and a hypometabolism in basal ganglia; [18F]FDG PET may identify a coexisting neurodegenerative disease, helping in patient selection for surgery; postsurgery increase in glucose metabolism was associated with clinical improvement. (4) Dopaminergic PET imaging showed a postsynaptic D2 receptor reduction and striatal upregulation of D2 receptor after treatment, associated with clinical improvement. Overall, PET imaging could be a useful tool in iNPH diagnoses and treatment response.

Characteristics of ganglion cells in pituitary gangliocytomas.

The occurrence of ganglion cells in the sella turcica, in association or not with a pituitary adenoma, has been rarely reported. Various names have been employed for this rare entity, gangliocytoma being frequently used and recommended by WHO classification. Expression of cytokeratin in these ganglion cells has been previously occasionally reported, a very intriguing observation raising questions on the possible nature and derivation of these cells. We describe the pathological findings in three cases of growth hormone-producing adenomas, all sparsely granulated, showing the presence of a ganglion cell population admixed with an adenomatous component. A review of the literature is also provided.

Efficacy of Microsurgical Sublabial Approach (MSA) Versus Endoscopic Endonasal Approach (EEA) for the Treatment of Pituitary Adenomas Based on Radiological and Hormonal Outcome.

BACKGROUND: The purpose of this study was to compare the surgical efficacy of the microsurgical sublabial approach (MSA) versus the endoscopic endonasal approach (EEA) for the treatment of pituitary adenomas, based on short-term (12 months) radiological and endocrinological follow-up. METHODS: One hundred and fourteen patients affected by pituitary adenoma were enrolled at our Unit between January 2007 and February 2012; 72 were treated with MSA, and 42 with EEA. The preoperative parameters considered were: type of lesion (secreting or nonsecreting), lesion size, presence of intralesional hemorrhage, lesion perimeter (nodular vs. uniform), intrasellar vs. suprasellar, involvement of cavernous sinus, and osteodural infiltration. Hormonal assays and magnetic resonance imaging (MRI) scans were performed at 12 months after the surgical procedure. RESULTS: Univariate analysis of the data documented a statistically significant difference in favor of MSA for the subgroups of secreting adenomas (90.9 % vs. nonsecreting 48.3 %), microadenomas (100 % vs. macroadenomas 57.1 %), adenomas without osteodural infiltration (87.5 % vs. 55.5 % with the infiltration) or those without intralesional hemorrhage (75 % vs. 45.9 % with the hemorrhage), and growth hormone (GH) adenomas (88.8 % vs. 43.7 %). Multivariate analysis confirmed the greater effectiveness of MSA for the treatment of micro-secreting adenomas. CONCLUSIONS: Recent advances in the EEA for treating pituitary adenomas could lead to this modality replacing the microsurgical technique. In our experience the MSA allowed us to achieve better results in the treatment of microadenomas.

Intracranial pressure wave morphological classification: automated analysis and clinical validation.

BACKGROUND: Recently, different software has been developed to automatically analyze multiple intracranial pressure (ICP) parameters, but the suggested methods are frequently complex and have no clinical correlation. The objective of this study was to assess the clinical value of a new morphological classification of the cerebrospinal fluid pulse pressure waveform (CSFPPW), comparing it to the elastance index (EI) and CSF-outflow resistance (Rout), and to test the efficacy of an automatic ICP analysis. METHODS: An artificial neural network (ANN) was trained to classify 60 CSFPPWs in four different classes, according to their morphology, and its efficacy was compared to an expert examiner's classification. The morphology of CSFPPW, recorded in 60 patients at baseline, was compared to EI and Rout calculated at the end of an intraventricular infusion test to validate the utility of the proposed classification in patients' clinical evaluation. RESULTS: The overall concordance in CSFPPW classification between the expert examiner and the ANN was 88.3 %. An elevation of EI was statistically related to morphological class' progression. All patients showing pathological baseline CSFPPW (class IV) revealed an alteration of CSF hydrodynamics at the end of their infusion test. CONCLUSIONS: The proposed morphological classification estimates the global ICP wave and its ability to reflect or predict an alteration in CSF hydrodynamics. An ANN can be trained to efficiently recognize four different CSF wave morphologies. This classification seems helpful and accurate for diagnostic use.

Typical and atypical pituitary adenomas: a single-center analysis of outcome and prognosis.

BACKGROUND AND OBJECTIVE: In 2004, the World Health Organization defined atypical pituitary adenomas as those with a Ki-67 expression > 3%, an excessive p53 expression and increased mitotic activity. As the usefulness of this classification is controversial, we reviewed typical and atypical pituitary adenomas to compare the clinical and prognostic features. PATIENTS AND METHODS: We retrospectively reviewed 343 consecutive pituitary adenomas. Atypical pituitary adenomas represented 18.7% of cases. All patients were operated on at the Department of Neurosurgery of our institution and were followed up at the Hypothalamic-Pituitary Disease Unit of the same institution. The median follow-up time was 75 months (range 7-345). RESULTS: Younger age at diagnosis as well as immunohistochemical positivity for adrenocorticotropic hormone and prolactin correlated with a higher risk of atypical pituitary adenomas, whereas typical and atypical pituitary adenomas did not differ with regard to gender, tumor size, recurrence risk and disease-free survival time (DFST). Among the 219 patients who underwent radical surgery, a Ki-67 expression ≥ 1.5% was associated with a higher risk of recurrence and a worse DFST, even after correction for age at diagnosis, gender, immunohistochemical classification, tumor size, invasiveness and Knosp classification [p = 0.01; hazard ratio (HR) 2.572; 95% confidence interval (CI) 1.251-5.285). Pituitary adenomas with a Ki-67 expression ≥ 1.5% showed a worse DFST as compared to pituitary adenomas with a Ki-67 expression < 1.5% (HR 2.166; 95% CI 1.154-4.064). CONCLUSION: In this series, atypical and typical pituitary adenomas did not differ with regard to recurrence and DFST. Pituitary adenomas with a Ki-67 expression ≥ 1.5% showed a higher recurrence risk and a worse DFST as compared to those with a Ki-67 expression < 1.5%. We suggest that a Ki-67 expression ≥ 1.5% may be useful as a prognostic marker, though this will need to be confirmed by prospective, multicenter data.

Radically resected pituitary adenomas: prognostic role of Ki 67 labeling index in a monocentric retrospective series and literature review.

Ki-67 Labeling Index is an immunocytochemical marker of cell proliferation. The correlation of Ki-67 expression with pituitary adenomas recurrence has been investigated and is highly debated. Aim of this study was to evaluate whether Ki-67 correlates with recurrence even in patients with an apparently completely removed pituitary adenoma. We retrospectively reviewed the database of the Hypothalamic-Pituitary Disease Unit at the Catholic University of Rome, collected between 2003 and 2011. Inclusion criteria were: patients who underwent surgery at the Department of Neurosurgery with an apparently complete removal of a pituitary adenoma; Ki-67 histological evaluation by the same operator and values of <3%. All patients underwent endocrine evaluation of the hypothalamic-pituitary function, ophthalmologic and neuro-radiological examinations, during the preoperative period and follow-up. Out of 490 patients recorded on the database of the Hypothalamic-Pituitary Disease Unit at the Catholic University of Rome, 191 cases met the inclusion criteria. Recurrence was observed in 49 cases (25.7% of the patients who had undergone radical excision). Optional cut-off value was identified at Ki-67 values of 1.50%. This was associated with worse disease-free survival time, even after correction for age at treatment, gender, positivity to p53, functional classification and Knosp grading. Ki-67 labeling index may be useful in postoperative management, even in patients who underwent radical PA removal. We suggest a Ki-67 cut-off value of 1.5% to plan an adequate clinical follow-up.

Early evaluation of cerebral metabolic rate of glucose (CMRglu) with 18F-FDG PET/CT and clinical assessment in idiopathic normal pressure hydrocephalus (INPH) patients before and after ventricular shunt placement: preliminary experience.

PURPOSE: We evaluated the relationships between the cerebral metabolic rate of glucose (CMRglu) measured by dynamic (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and the clinical and neuropsychological assessment before and after the surgical procedure in idiopathic normal pressure hydrocephalus (INPH) patients. METHODS: Eleven selected INPH patients underwent clinical assessment (modified Rankin scale, Krauss scale, Larsson categorization system and Stein-Langfitt scale), cognitive evaluation (Mini-Mental State Examination, MMSE) and dynamic (18)F-FDG PET/CT scan 3 days before and 1 week after ventricular shunt placement. RESULTS: After shunting, the global CMRglu significantly increased (2.95 ± 0.44 vs 4.38 ± 0.68, p = 10(-7)) in all INPH patients with a mean percentage value of 48.7%. After shunting, no significant change was found in the Evans ratio whereas a significant decrease in all clinical scale scores was observed. Only a slight reduction in the MMSE was found. After shunting, a significant correlation between the global CMRglu value and clinical assessment was found (R (2) = 0.75, p = 0.024); indeed all clinical scale scores varied (decreasing) and the CMRglu value also varied (increasing) in all INPH patients. CONCLUSION: Our preliminary data show that changes in the CMRglu are promptly reversible after surgery and that there is a relationship between the early metabolic changes and clinical symptoms, independently from the simultaneous changes in the ventricular size. The remarkable and prompt improvement in the global CMRglu and in symptoms may also have important implications for the current concept of "neuronal plasticity" and for the cells' reactivity in order to recover their metabolic function.

Treatment with octreotide LAR in clinically non-functioning pituitary adenoma: results from a case-control study.

Surgical cure cannot be achieved in most patients with invasive non-functioning pituitary macroadenoma (NFPA). Short-term residual tumor treatment with somatostatin analogs has produced disappointing results. This prospective case-control study assessed the efficacy of chronic treatment with long acting octreotide (octreotide LAR) on tumor volume in patients harboring post-surgical NFPA residue. The study population comprised 39 patients with NFPAs not cured by surgery. All patients underwent somatostatin receptor scintigraphy at least 6 months after the last surgery. Patients with a positive pituitary level octreoscan at (n = 26) received octreotide LAR (20 mg every 28 days) for ≥ 12 months (mean follow-up 37 ± 18 months) (Treated group). Moreover, a fragment of tumor tissue from patients in the treated group was retrospectively collected to assess the immunohistochemical expression of somatostatin receptor subtypes (SSTRs). The patients with a negative octreoscan (n = 13) formed the control group (mean follow-up 37 ± 16 months). Hormonal, radiological and visual field parameters were periodically assessed. In the treated group, all tumors expressed at least one SSTR subtype. The SSTR5 subtype was the most abundant, followed by SSTR3. The tumor residue increased in five of 26 patients (19%) in the treated group and in seven of 13 controls (53%). Visual field and pituitary function did not change in any patient. This study indicates that SSTR5 and SSTR3 are the most frequently expressed SSTR subtypes in NFPAs and supports a potential role of SSTR subtypes in stabilization of tumor remnant from NFPAs.

Safety and efficacy of Gliadel wafers for newly diagnosed and recurrent glioblastoma.

BACKGROUND: Combining Gliadel wafers and radiochemotherapy with TMZ may carry the risk of increased adverse events (AE). We analyzed the efficacy and safety in patients with glioblastoma who underwent multimodal treatment with implantation of Gliadel wafers. METHODS: One hundred sixty-five consecutive patients with newly diagnosed (77 patients) or recurrent (88 patients) glioblastoma were studied. Forty-seven patients underwent surgery + Gliadel. The impact of age (≥65 vs. <65), resection extent (gross total vs. partial), use of Gliadel and adjuvant treatment (TMZ vs. other schemes/no adjuvant therapy) on overall survival (OS, for patients with newly diagnosed glioblastoma) and on recurrence-survival (for patients with recurrent glioblastoma) was analyzed with Cox regression. The impact of age, history (newly diagnosed vs. recurrent glioblastoma), number of Gliadel wafers implanted (0 vs. <8 vs. 8), resection extent (gross-total vs. partial) and adjuvant treatment (TMZ vs. other schemes/no adjuvant therapy) on the occurrence of AE and on the occurrence of implantation site-related AE (ISAE) was analyzed with the logistic regression model. Significance was set at p < 0.05. RESULTS: Multivariate analysis showed the only factor associated with longer survival, both for newly diagnosed and for recurrent GBM, was resection extent. Both patients with a higher number of wafers implanted and patients with recurrent tumors were significantly at risk for AE and ISAE. Patients with eight Gliadel wafers implanted had a 3-fold increased risk of AE and a 5.6-fold increased risk of ISAE, and patients with recurrent tumor had a 2.8-fold increased risk of AE and a 9.3-fold increased risk of ISAE. CONCLUSIONS: Adding Gliadel to standard treatment did not significantly improve the outcome. The toxicity after Gliadel use was significantly higher, both for patients with newly diagnosed and patients with recurrent glioblastoma.

Clinical and radiological outcomes following open door laminoplasty: a single center evolution of the technique.

BACKGROUND: The aim of the present study was to compare and describe clinical and radiological outcomes after two different variants of open door laminoplasty for cervical spondylotic myelopathy (CSM). METHODS: Fifty-five patients underwent cervical laminoplasty for CSM. Between 2005 to 2009, 32 patients underwent open-door laminoplasty (Group A) performed with a monolateral exposure with contralateral "green stick" laminar fracture. A technical variant consisting in bilateral exposure, spinous process removal and symmetrical muscular closure was applied in the other 23 (Group B), from 2009 to 2016. A retrospective analysis of surgical results between the two groups was performed. RESULTS: In group B, the mean operative time was longer, and the mean volume of intraoperative blood loss was much higher than in group A. Both differences were not significant (P=0.1601 and P=0.0884, respectively). The average hospitalization was non-significantly longer in group B (7.3±1.8 vs. 6.5±1.6 d; P=0.0947). Postoperatively, axial neck pain was more severe in group A at last follow-up than preoperatively (P>0.05). mJOA scores and Nurick grades improved significantly in both groups at last follow-up; in group A, the mean recovery rates were 41.5% by mJOA scores and 29.4% by Nurick grades, whereas in group B they were 52.7% and 36.8%, respectively. CONCLUSIONS: Applying some few variations to a standard monolateral approach, although slightly more time and blood consuming, could reduce the incidence of long-term axial symptoms and, in our experience, are not burdened by worsening of outcomes. A prospective, multicentric study with a longer follow-up should be conducted in order to confirm our findings.

Impact of 4K ultra-high-definition endoscope in pituitary surgery: analysis of a comparative institutional case series.

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

Whole-brain radiotherapy combined with surgery or stereotactic radiotherapy in patients with brain oligometastases: long-term analysis.

OBJECTIVE: To verify whether the treatment of brain oligometastases with whole-brain radiotherapy (WBRT) plus stereotactic radiotherapy (SRT) or surgical resection results in different outcomes. METHODS: Files of patients affected by brain metastases submitted to surgical resection followed by WBRT (group A) or WBRT + SRT (group B) were retrospectively selected for this study. The two treatment groups were matched for the following potential prognostic factors: WBRT schedule, age, gender, performance status, tumor type, number of brain metastases, extra-cerebral metastases, and recursive partitioning analysis class (RPA). The outcomes of patients in both groups were evaluated in terms of toxicity, local control, and overall survival. RESULTS: Total of 97 patients were selected (56 male; 42 female) who were respectively submitted to surgical resection followed by WBRT (group A, n = 50 patients) or WBRT + SRT (Group B, n = 47 patients). Median follow-up was 95 months (range, 8-171 months). The 1-year local control rates were 46.0% and 69.0% respectively. No significant difference in local tumor control was observed between group A and B (p = 0.10). Median overall survival was 15 and 19 months in group A and B, respectively. One-year survival was 56.0% and 62%, respectively. No difference was observed in the two groups (p = 0.40). CONCLUSION: Surgery remains the main therapeutic approach in symptomatic patients; nevertheless, our data support the use of WBRT plus SRT in one or two brain metastases smaller than 3 cm.

Long-standing Overt Ventriculomegaly in Adults and Endoscopic Third Ventriculostomy, the Perfect Treatment for the Proper Diagnosis.

OBJECTIVE: Long-standing overt ventriculomegaly in adults (LOVA) is form of hydrocephalus that develops during childhood, manifesting its symptoms during adulthood. Only a small number of LOVA case series have been published, and controversies regarding optimal management still exist. The authors collected a series of symptomatic LOVA patients treated successfully using endoscopic third ventriculostomy (ETV), aiming to strengthen what has been reported in the literature on ETV's role in both neurologic and neurocognitive outcomes. METHODS: Between 2002 and 2020, we collected 40 case studies of patients treated using an ETV. Associated pathologies were documented in 14 cases. All patients underwent magnetic resonance scans preoperatively and postoperatively while only 29 patients were submitted during follow-up to neurocognitive assessment. RESULT: At a mean follow-up of 6 years, 36 patients (90%) reported either an improvement or a stabilization of their presenting symptoms. Headache improved subjectively in 11 patients (27.5%), balance and gait disturbances improved in all patients, urinary incontinence improved in 24 patients (60%), memory disturbances subjectively improved in 21 patients (52.5%), and visual deficits improved in 5 patients (12.5%). Four patients (10%) had symptom progression, which occurred 6 to 24 months after surgery with radiologic evidence of ETV failure. CONCLUSIONS: LOVA is a form of hydrocephalus that must be correctly identified. A correct magnetic resonance study and comprehensive neuropsychologic assessment are crucial to identify it in order to define proper management. From our analysis, ETV represents the gold standard treatment granting rewarding results that are maintained in a long-term follow-up.

Do antiplatelet and anticoagulant drugs modify outcome of patients treated for chronic subdural hematoma? Still a controversial issue.

BACKGROUND: Anticoagulants (ACs) and antiplatelet aggregation agents (AAAs) seem to be correlated to a higher incidence of chronic subdural hematoma (CSDH) but whether or not they contribute to its recurrence is debated. Few data are available on clinical outcomes and indications for the management of this therapy are not so well defined. We investigated the role of ACs and AAAs in modifying patients' clinical outcomes treated for CSDH, especially for re-bleedings. METHODS: This retrospective study, enrolled patients treated for CSDH. Patients characteristics were recorded including drugs used (antiplatelet/anticoagulant) and clinical conditions (Modified Rankin Scale [mRS]) upon admission. Patients underwent surgery (burrhole vs. minicraniectomy) with subdural drainage positioning. Clinical/radiological follow-ups were performed at one and six months. Chi-square/Fisher's Exact test were used to compare variables and stepwise backward logistic regression analysis was used for defining their impact on complications, risk of re-bleeding and reoperation. RESULTS: Overall, 230 patients (45 on ACs, 76 on AAAs and nine on both) were enrolled. Higher mRS scores were significantly associated with a higher risk of general complications (OR=3.78, 95% CI: 1.66-8.62, P=0.002), higher risk of rebleeding (OR =15.82, 95% CI: 4.33-57.90, P<0.001) and re-operation (OR=11.39, 95% CI: 3.35-37.56, P<0.0001). No statistically significant association was found between AAAs or ACs and complications or re-bleedings or risk of reoperation. CONCLUSIONS: AAAs and ACs alone do not seem to worsen the clinical outcome or increase re-bleedings. mRS may be a predicting factor, since patients with higher scores showed a worse outcome and an increased risk of re-bleeding, general complications and reoperation.

Reappraising the Role of Trans-Sphenoidal Surgery in Prolactin-Secreting Pituitary Tumors.

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

Galectin-3 and Estrogen Receptor Alpha as Prognostic Markers in Prolactinoma: Preliminary Results From a Pilot Study.

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