Epidemiology-based evaluation of trends in treatment for ruptured intracranial aneurysms in Italy

Background: In recent years there have been significant advances in the diagnosis, management and treatment of intracranial aneurysms (IAs) in Italy. Changes in prevalence of several epigenetic risk factors in the population as well as in environmental factors may have influenced the epidemiological burden of this disease. No long-term, population-based study about the incidence of treated ruptured IAs (rIAs) in Italy has yet been reported in literature. Methods: A long-term (January 2015 - December 2020), nationwide epidemiology study was performed by using discharge data collected by the Italian National Agency for Regional Healthcare Services with a particular focus on the treatment incidence of rIAs. A sub-analysis per macro-areas (north, center, and south and islands) was also performed, including the data about regional healthcare systems organization. The prevalence of common epigenetic and environmental risk factors has been also assessed. Results: Over 6 years, the mean incidence of rIAs treatment was 2.7 x 100.000 per year (ds ± 0.1; range: 2.6-2.9). In 2020, there was a significant north-south decreasing gradient in incidence (north vs center vs south and islands: 3.4 vs 2.4 vs 1.8 x 100.000/year; all p<0.001). There were no meaningful differences between macro-areas in terms of access to emergency care and number of neurosurgical wards per population. The rate of unruptured IAs (uIAs) treatment did not show a correlation to that of ruptured ones. Minor regional differences were retrieved for high-risk hypertension as well as for alcohol abuse prevalence. Air pollutants and temperature charts showed a north-south gradient similar to that of the incidence in the treated rIAs. Conclusions: The mean incidence of treated rIAs was stable over the 2015-2020 period in Italy. A north-south decreasing gradient in rIAs treatment incidence was reported. Neither the Regional healthcare organizations nor the rate of uIAs treatment were significant factors explaining the regional differences in the incidence of rIAs treatment. Minor differences in epigenetic and environmental risk factors may be synergistically involved

Fluorophores Use in Pituitary Surgery: A Pharmacokinetics and Pharmacodynamics Appraisal

(1) Background: Despite many surgical and technological advances, pituitary adenoma surgery is still burdened by non-negligible rates of incomplete tumor resection, mainly due to difficulties in differentiating pathology from normal pituitary tissue. Some fluorescent agents have been recently investigated as intraoperative contrast agents in pituitary surgery. The aim of this study is to evaluate the actual knowledge about the usefulness of such fluorophores with a particular focus on both the pharmacokinetics and pharmacodynamics issues of the pituitary gland. (2) Methods: We reviewed the current literature about fluorophores use in pituitary surgery and reported the first fully endoscopic experience with fluorescein. (3) Results: The studies investigating 5-ALA use reported contrasting results. ICG showed encouraging results, although with some specificity issues in identifying pathological tissue. Low-dose fluorescein showed promising results in differentiating pathology from normal pituitary tissue. Apart from the dose and timing of administration, both the fluorophores’ volume of distribution and the histological variability of the interstitial space and vascular density played a crucial role in optimizing intraoperative contrast enhancement. (4) Conclusions: Both pharmacokinetics and pharmacodynamics issues determine the potential usefulness of fluorophores in pituitary surgery. ICG and fluorescein showed the most promising results, although further studies are needed

Fluorescein-aided neurosurgery

Neurosurgery made enormous advances over the last century. Moving from a meticulous anatomical knowledge of the cerebral structures and passing through the “microscope revolution” we arrived in the modern neuronavigation era in which we can render and correlate real-time the preoperative imaging to the patient. Real life, though, is way different from simulation and technological promises. In fact, some tumours are still almost undistinguishable from the brain in normal vision and our individual estimate of vessel patency may be proved way wrong at the ischemic post operative imaging. Sometimes, even with all the best resources, we are blindly performing life-saving procedures. The development of fluorescent intra-operative tracers tried to address these issues. This PhD thesis is, basically, the synthesis of three years of personal clinical experience on the experimental use of intra-operative Fluorescein in Neurosurgery. Briefly, I will describe the optical and pharmaceutical properties of Fluorescein and explain how I assembled a low-cost fluorescence detection system. Then I will go through all the fields of Neurosurgery in which I applied this technology. Firstly, I will report the preliminary results of an ongoing Clinical Trial on the use of Fluorescein as an intra-operative contrast enhancer of the borders of high grade glioma tumours. Then, the potential advantages of fluorescein use in vascular neurosurgery will be discussed. In particular the use of fluorescein for the evaluation of the exclusion of intra-cerebral aneurysms will be illustrated by means of an explicative case. Similarly, I will report the usefulness of intra-operative fluorescence detection in a case of intra-cerebral cavernoma. Lastly, I will describe the experience of fluorescein staining in the field of Hereditary hemorrhagic telangiectasia and explain the potential advantages of this technique in arteriovenous malformations. Eventually, I will describe the usefulness of dedicated endoscopic filters for fluorescein detection in trans-nasal skull base procedures. The rationale and preliminary results of the use of fluorescein as an intra-operative contrast medium in pituitary adenoma surgery will be presented. CSF leak detection and pedicled flaps' perfusion evaluation techniques will be also described in detail.Neurosurgery made enormous advances over the last century. Moving from a meticulous anatomical knowledge of the cerebral structures and passing through the “microscope revolution” we arrived in the modern neuronavigation era in which we can render and correlate real-time the preoperative imaging to the patient. Real life, though, is way different from simulation and technological promises. In fact, some tumours are still almost undistinguishable from the brain in normal vision and our individual estimate of vessel patency may be proved way wrong at the ischemic post operative imaging. Sometimes, even with all the best resources, we are blindly performing life-saving procedures. The development of fluorescent intra-operative tracers tried to address these issues. This PhD thesis is, basically, the synthesis of three years of personal clinical experience on the experimental use of intra-operative Fluorescein in Neurosurgery. Briefly, I will describe the optical and pharmaceutical properties of Fluorescein and explain how I assembled a low-cost fluorescence detection system. Then I will go through all the fields of Neurosurgery in which I applied this technology. Firstly, I will report the preliminary results of an ongoing Clinical Trial on the use of Fluorescein as an intra-operative contrast enhancer of the borders of high grade glioma tumours. Then, the potential advantages of fluorescein use in vascular neurosurgery will be discussed. In particular the use of fluorescein for the evaluation of the exclusion of intra-cerebral aneurysms will be illustrated by means of an explicative case. Similarly, I will report the usefulness of intra-operative fluorescence detection in a case of intra-cerebral cavernoma. Lastly, I will describe the experience of fluorescein staining in the field of Hereditary hemorrhagic telangiectasia and explain the potential advantages of this technique in arteriovenous malformations. Eventually, I will describe the usefulness of dedicated endoscopic filters for fluorescein detection in trans-nasal skull base procedures. The rationale and preliminary results of the use of fluorescein as an intra-operative contrast medium in pituitary adenoma surgery will be presented. CSF leak detection and pedicled flaps' perfusion evaluation techniques will be also described in detail

Fluorescein-guided intraoperative endoscopy in patients with hereditary hemorrhagic telangiectasia: first impressions

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is a rare genetic disease that results in mucocutaneous telangiectasias and arteriovenous visceral malformations. Nasal telangiectasias lead to recurrent epistaxis, which affects up to 96% of patients. Different morphologic classifications and methods of visualization of nasal lesions have been described in the literature. We developed a new method of intraoperative endoscopy based on the intravenous administration of fluorescein. Preliminary data of this technique are reported. METHODS: After the intravenous administration of sodium fluorescein, an intraoperative fluorescein-guided endoscopy was carried out using photographic customized yellow filters on top of a 0-degree, 4-mm endoscope. RESULTS: In 2015, 65 HHT patients underwent surgery for their epistaxis in our institution, and in 7 patients (3 males, 4 females; mean age, 54 years) an intraoperative fluorescein-guided intraoperative nasal endoscopy was performed. No adverse events or complications were observed. CONCLUSION: First impressions regarding the usage of this technique in HHT patients seem to be promising and positive in terms of efficacy and safety. However, further studies with larger cohorts of patients should be performed in order to better investigate the use of this method for diagnostic and surgical purposes in HHT

Outcome of elderly patients undergoing intracranial meningioma resection: a single center experience

Higher life expectancy and higher mean age in general population created growing interest in medical and surgical management of meningiomas in elderly. It is well known that, due to possible complications, pre-operative status and comorbidities, expecially in aged people, should be carefully considerated in the decision-making process. We described our experience with this kind of patients and analized the influence of complications on the outcome