The Preoperative Paradoxical GH Response to Oral Glucose Load Predicts a low Risk of Recurrence in Acromegaly.

CONTEXT: a paradoxical growth hormone (GH) response to oral glucose load (OGTT) in acromegaly is associated with a milder phenotype. OBJECTIVE: To study whether the GH response to OGTT predicts the risk of recurrence after initial surgical cure. DESIGN: Retrospective, observational study. SETTING: Two tertiary care centers. PATIENTS: We investigated 254 patients with acromegaly who were cured by surgery. INTERVENTION: All patients underwent OGTT at diagnosis before pituitary surgery. A peak-to-basal GH ratio ≥ 120% within 90 minutes was used to distinguish paradoxical (GH-Par) from non-paradoxical acromegalic patients (GH-NPar). MAIN OUTCOME MEASURE: Cox analysis was used to investigate whether the paradoxical GH response to OGTT was associated with the risk of disease recurrence. RESULTS: A paradoxical GH response to OGTT occurred in 87 patients (34.3%, termed GH-Par group). Recurrence of acromegaly occurred in three patients of the GH-Par group (3.4%) and in 20 patients in the GH-NPar group (12.0%). In the multivariate analysis, the paradoxical GH response to OGTT was significantly associated with the risk of recurrence (HR 0.18, 95% CI, 0.05-0.63; P = 0.007). Basal GH level at diagnosis was the only other variable associated with the risk of disease recurrence (HR 1.58, 95% CI, 1.01-2.47; P = 0.04). CONCLUSIONS: our study demonstrates that a paradoxical GH response to OGTT in the preoperative setting predicts a lower risk of disease recurrence after initial surgical cure. The pattern of GH responsiveness to OGTT is, therefore, useful to predict the long-term outcome of patients with acromegaly.

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.

Gamma Knife radiosurgery for central neurocytoma: a quantitative systematic review and metanalysis.

Central neurocytomas (CN) are rare tumors within the central nervous system. Originating from the septum pellucidum and subependymal cells, they are typically found in the third and lateral ventricles. For this reason, they may lead to hydrocephalus and increased intracranial pressure. CNs are generally benign lesions that exhibit locally aggressive behavior and a high recurrence rate. Complete surgical resection is the preferred treatment; however, due to their anatomical location, this is often not feasible. Based on these findings, Gamma Knife radiosurgery (GKRS) has been introduced for managing both residual and recurrent tumors and as an initial therapy in selected cases. This study aimed to systematically review the available knowledge regarding GKRS for CN. A systematic investigation of the scientific literature was undertaken through an exhaustive search across prominent databases, including PubMed, Web of Science, and Google Scholar, by employing precise MeSH terms such as "Central neurocytoma," "Radiosurgery," "Gamma Knife," and "Stereotactic Radiosurgery." A comprehensive quantitative systematic review and meta-analysis were meticulously conducted, focusing on cases of CN treated with GKRS for a thorough evaluation of outcomes and efficacy. Seventeen articles, including 289 patients, met the inclusion criteria. Random effects meta-analysis estimates for disease control and local tumor control were 90% (95% CI 87-93%; I2 = 0%, p < 0.74) and 94% (95% CI 92-97%; I2 = 0%, p < 0.98), respectively. When considering only studies with at least 5 years of follow-up, progression-free survival was 89% (95% CI 85-94%; I2 = 0.03%, p < 0.74). The mean clinical control rate was 96%. This systematic review and meta-analysis confirmed the safety and efficacy of GKRS in managing CN.

Primary Gamma Knife Radiosurgery for pineal region tumors: A systematic review and pooled analysis of available literature with histological stratification.

Pineal region tumors (PTs) represent extremely rare pathologies, characterized by highly heterogeneous histological patterns. Most of the available evidence for Gamma Knife radiosurgical (GKSR) treatment of PTs arises from multimodal regimens, including GKSR as an adjuvant modality or as a salvage treatment at recurrence. We aimed to gather existing evidence on the topic and analyze single-patient-level data to address the efficacy and safety of primary GKSR. This is a systematic review of the literature (PubMed, Embase, Cochrane, Science Direct) and pooled analysis of single-patient-level data. A total of 1054 original works were retrieved. After excluding duplicates and irrelevant works, we included 13 papers (n = 64 patients). An additional 12 patients were included from the authors' original series. A total of 76 patients reached the final analysis; 56.5% (n = 43) received a histological diagnosis. Confirmed lesions included pineocytoma WHO grade I (60.5%), pineocytoma WHO grade II (14%), pineoblastoma WHO IV (7%), pineal tumor with intermediate differentiation WHO II/III (4.7%), papillary tumor of pineal region WHO II/III (4.7%), germ cell tumor (2.3%), neurocytoma WHO I (2.3%), astrocytoma WHO II (2.3%) and WHO III (2.3%). Presumptive diagnoses were achieved in the remaining 43.5% (n = 33) of cases and comprised of pineocytoma (9%), germ cell tumor (6%), low-grade glioma (6%), high-grade glioma (3%), meningioma (3%) and undefined in 73%. The mean age at the time of GKSR was 38.7 years and the mean lesional volume was 4.2 ± 4 cc. All patients received GKSR with a mean marginal dose of 14.7 ± 2.1 Gy (50% isodose). At a median 36-month follow-up, local control was achieved in 80.3% of cases. Thirteen patients showed progression after a median time of 14 months. Overall mortality was 13.2%. The median OS was not reached for all included lesions, except high-grade gliomas (8mo). The 3-year OS was 100% for LGG and pineal tumors with intermediate differentiation, 91% for low-grade pineal lesions, 66% for high-grade pineal lesions, 60% for germ cell tumors (GCTs), 50% for HGG, and 82% for undetermined tumors. The 3-year progression-free survival (PFS) was 100% for LGG and pineal intermediate tumors, 86% for low-grade pineal, 66% for high-grade pineal, 33.3% for GCTs, and 0% for HGG. Median PFS was 5 months for HGG and 34 months for GCTs. The radionecrosis rate was 6%, and cystic degeneration was observed in 2%. Ataxia as a presenting symptom strongly predicted mortality (odds ratio [OR] 104, p = .02), while GCTs and HGG histology well predicted PD (OR: 13, p = .04). These results support the efficacy and safety of primary GKSR treatment of PTs. Further studies are needed to validate these results, which highlight the importance of the initial presumptive diagnosis for choosing the best therapeutic strategy.

Innovative Calcium Carbonate-Based Products to Repair Cracked Cement Mortars.

The durability of Portland cement mortars is often affected by environmental factors, which can cause physicochemical and mechanical degradation processes. In this study, the performance of three products, calcium acetoacetate and calcium tetrahydrofurfuryloxide dissolved in two different solvents developed and tested as stone consolidants, was evaluated in terms of crack filling or sealing and consolidation. Realistic cracks were induced in quasibrittle cement mortar prisms using a custom-designed test rig. The effectiveness and the performance of the considered treatments, investigated on specimens, were evaluated by optical and scanning electron microscopy, colourimetry, water absorption rate, ultrasonic pulse velocity, and surface hardness measurements. Results revealed that, in the examined conditions, the products were more suitable as surface consolidants than as crack fillers.

Normal Insulin-like Growth Factor 1 During Somatostatin Receptor Ligand Treatment Predicts Surgical Cure in Acromegaly.

CONTEXT: Treatment with somatostatin receptor ligands (SRLs) is often given before pituitary surgery to patients with acromegaly. OBJECTIVE: To study whether the response to treatment with SRLs is predictive of surgical outcome. DESIGN: Retrospective, observational study. SETTING: Tertiary care center. PATIENTS: We investigated 272 patients with acromegaly who had been treated with an SRL between 1990 and 2018. INTERVENTION: All patients underwent pituitary surgery performed by a skilled neurosurgeon. MAIN OUTCOME MEASURE: Outcome of pituitary surgery in patients who had normalization of insulin-like growth factor 1 (IGF-1) levels during SRL therapy in comparison with patients who did not normalize IGF-1 levels. RESULTS: Normalization of IGF-1 levels during SRL treatment occurred in 62 patients (22.8%) and was similar for the 3 different types of SRL (P = .88). Surgical remission occurred in 59.6% of the patients. Patients who normalized IGF-1 levels during SRL treatment had a higher probability of surgical cure than patients without IGF-1 normalization (83.9% vs 52.4%, respectively; P < .001). Multivariate analysis confirmed that lack of cavernous sinus invasion, small maximum tumor diameter, and IGF-1 normalization during SRL therapy were the only factors independently associated with a favorable surgical outcome. CONCLUSIONS: Our study demonstrates that the normalization of IGF-1 levels during treatment with SRLs is an independent predictive factor of a favorable surgical outcome. The underlying mechanisms remain unclear, but an optimal response to medical therapy may be a characteristic of less aggressive tumors that are more likely to be entirely removed at surgery.