Ovarian hyperthecosis coexisting with an incidental adrenal lesion: challenges in the diagnostic approach

Ovarian hyperthecosis is the most common cause of hyperandrogenism in women during postmenopausal age. However, its diagnosis is frequently challenging, since several causes must be ruled out, involving both adrenal glands and ovaries. Herein we describe the case of a 62 years old woman addressed to our Unit after the casual detection of an adrenal mass, compatible with an adenoma. Biochemical evaluation revealed gonadotropins in menopausal range, high testosterone and androstenedione, while the patient had been complaining of androgenetic alopecia and hirsutism for some years. Ultrasound imaging revealed only a small increase in ovarian volume, in relationship to the patient’s age. A GnRHa test was performed, demonstrating gonadotropins suppression and testosterone normalization, thus confirming the suspect of ovarian hyperthecosis. The administration of these agonists, together with the slow progression of symptoms over years, play a fundamental role into excluding an androgen-secreting neoplasia, also limiting the use of ovarian veins catheterization as second line test. Besides, they represent a valid therapeutical option, especially when surgery is contraindicated (or cannot be performed)

Hashimoto’s thyroiditis, hypoparathyroidism and coeliac disease: lessons from a rare association

We present the case of a 36 years old woman, affected by euthyroid Hashimoto’s thyroiditis (HT) from the age of 20. She reported the following symptoms for three years: weight reduction, abdominal pain, alternate constipation and diarrhoea, tiredness, paresthesias and cramps. Biochemical evaluation revealed low iron levels (21 ug/dl, with microcytic anemia) and hypocalcemia (6.6 mg/dl), first attributed to coeliac disease (EMA IgG, AGA IgG-A and tTG IgA positivity; Marsh-Oberhuber 3a/3b type at duodenal biopsy). TSH, PTH and 25-OHD3 were in the normal range. Although the patient was on a gluten-free diet for the second year, cramps persisted and facial spasms and tetanic crises appeared. One year later she came to our attention with severe hypocalcemia (Ca 5.1 mg/dl, Ca++ 0.6 nmol/L) and low PTH (2.5 pg/ml). A diagnosis of primary hypoparathyroidism was made and conventional treatment was started. In the following months, symptomatic hypocalcemia persisted (6.7 mg/dl, Ca++ 0.7 nmol/L), despite the gradual increase of calcium and calcitriol supplements. Gastro-intestinal re-evaluation demonstrated gluten contamination, so as to hypothesize that the scarce dietary compliance had caused persistent malabsorption and had made the hypocalcemia difficult to manage. The observation of these three disorders coexisting in a single patient, never reported by the literature, warns us about the virtually unlimited possibilities of autoimmune disease clustering. Clinicians should be aware of the increased risk of developing additional AIDs in patients with one autoimmune disorder

Nano-drugs and imaging guided surgery in multimodal treatment protocol of glioblastoma: a translational approach.

Primary brain tumors are a major cause of morbidity and mortality in the United States. Approximately one-third of tumors are malignant and the remaining are benign or borderline malignant. High-grade glioma, in particular glioblastoma, management is a great challenge for both neurosurgeons and patients. More than 45% of CNS primary malignant tumours are glioblastoma and their 5 year-survival is only 5% on average. Although biomolecular differences between glioblastoma IDH-WT and IDH-mutant might account for different outcomes, treatment strategies, including surgical EOR, chemiotherapy and radiotherapy, are currently considered important factors associated with PFS and OS. objective of this thesis is the definition of a neuro-oncological protocol, to be reserved for patients with glioblastoma, which can establish a therapeutic path that starts with a safe and effective surgery and continues with a pharmacological treatment that may lead to the limitations of current antitumor therapy schemes. Two main research lines have been conducted, with these purposes: the first one, essentially clinical, has been analysed in two consecutive studies, first retrospectively, then prospectively, the results of the application of an intraoperative imaging protocol that foresees the use of Advanced neuronavigation, intraoperative fluorescence and intraoperative CT. The second line of research was instead based on the attempt to obtain a pharmacological preparation which provided for the combination of temozolomide with nano-vectors, able to increase its antiblastic efficacy and to increase its chances of delivery at the intracranial level

Neuroprotective Properties of a Macrolide Antibiotic in a Mouse Model of Middle Cerebral Artery Occlusion:Characterization of the Immunomodulatory Effects and Validation of the Efficacy of Intravenous Administration

Repurposing the macrolide antibiotic azithromycin has recently been suggested as a promising neuroprotective strategy for the acute treatment of ischemic stroke. Here, we aim at further characterizing the immunomodulatory properties of intraperitoneal (i.p.) administration of this drug and, more importantly, at assessing whether neuroprotection can also be achieved by the more clinically relevant intravenous (i.v.) route of administration in a mouse model of focal cerebral ischemia induced by transient (30-min) middle cerebral artery occlusion (MCAo). A single i.p. injection of azithromycin (150 mg/kg) upon reperfusion prevented ischemia-induced spleen contraction and increased the number of MAC-1-immunopositive microglia/macrophages in the ischemic hemisphere 48 h after the insult. This was paralleled by an elevation of alternatively activated phenotypes (i.e., Ym1-immunopositive M2-polarized cells) and by a reduced expression of the pro-inflammatory marker myeloperoxidase. More importantly, i.v. administration of azithromycin upon reperfusion reduced MCAo-induced infarct volume and cerebral edema to an extent comparable to that obtained via the i.p. route. Although the i.p. route is often used for research purposes, it is impractical in the clinical setting; however, i.v. administration can easily be used in ischemic stroke patients who usually have i.v. access already established on hospital admission. The neuroprotective efficacy of the clinically relevant i.v. administration of azithromycin, together with its beneficial immunomodulatory properties reported in mice subjected to transient MCAo, suggests that this macrolide antibiotic can be effectively repurposed for the acute treatment of ischemic stroke. To this end, further work is needed to validate the efficacy of azithromycin in the clinical setting

Role of i-CT, i-US, and Neuromonitoring in Surgical Management of Brain Cavernous Malformations and Arteriovenous Malformations: A Case Series

OBJECTIVE: We retrospectively reviewed the institutional experience in patients who underwent microsurgical resection of cavernous malformations (CMs) or arteriovenous malformations (AVMs) using a multimodal intraoperative protocol including neuronavigation, intraoperative ultrasound (i-US), computed tomography (i-CT), and neuromonitoring.METHODS: Twenty-four patients (14 male), with a mean age of 47.5 years (range 27 - 73), have been included: 20 of them suffered from CMs and 4 suffered from AVMs.Neuromonitoring was used in 18 cases, when lesions were located in eloquent areas; 2 patients underwent awake craniotomy. First, an i-CT scan with and without contrast was acquired after patient positioning. Navigated B-mode ultrasound acquisition was carried out after dural opening to identify the lesion (CMs or AVMs nidus). Following identification and resection of vascular lesions, postcontrast i-CT (or CT-angio) was performed to detect and localize any small or calcified remnant (in cases of CMs) or residual vessels feeding the nidus (in cases of AVMs).RESULTS: In 5 cases of CMs and in 1 case of AVM, i-CT identified small residual lesions. In these cases, new i-CT images were uploaded into the navigation system and used for further resection. i-US was useful before starting transsulcal or transcortical approach to identify the lesions and guide the trajectory of the approach. However, several artifacts were observed during subsequent steps of dissection, making image interpretation difficult.CONCLUSIONS: The combination of different intraoperative real-time imaging modalities (i-CT and i-US), coupled with neuromonitoring, in the surgical management of vascular lesions, particularly if located in eloquent areas, has a positive impact on clinical outcome

Intraoperative Computed Tomography, navigated ultrasound, 5-Amino-Levulinic Acid fluorescence and neuromonitoring in brain tumor surgery: overtreatment or useful tool combination?

Brain tumor surgery is routinely supported by several intraoperative techniques, such as fluorescence, brain mapping and neuronavigation, which are often used independently. Efficacy of navigation is limited by the brain-shift phenomenon, particularly in cases of large or deep-sited lesions. Intraoperative imaging was introduced also to update neuronavigation data, to try and solve the brain-shift phenomenon-related pitfalls and increase overall safety. Nevertheless, each intraoperative imaging modality has some intrinsic limitations and technical shortcomings, making its clinical use challenging. We used a multimodal intraoperative imaging protocol to update neuronavigation, based on the combination of intraoperative Ultrasound (i-US) and intraoperative Computed Tomography (i-CT) integrated with 5-ALA fluorescence and neuromonitoring-guided resection

Penetrating aortic injury left untreated for 20 days: a case report

Abstract Background Penetrating aortic trauma remains one of the most challenging injuries with a high mortality rate if left untreated, or if the surgical treatment is delayed. We present an uncommon case of a late diagnosed abdominal firearm injury, in which the bullet partially penetrated the wall of the aorta, creating a plug that prevented immediate death due to massive bleeding. Case presentation A 26-year-old Libyan man was a victim of a firearm wound, with a bullet penetrating his abdominal wall from the left to right side. After the assault, the victim, spent up to 20 days crossing the Mediterranean Sea to leave his country of origin. Abdominal radiography revealed the presence of a bullet located anteriorly to the second lumbar vertebra, while computed tomography angiography, unexpectedly, demonstrated that the bullet penetrated partially into the aortic wall at the level of the left renal artery. The bullet penetrated the aortic wall for half of its length, creating a plug that avoided immediate life-threatening bleeding at the time of the gunshot injury. The bullet was removed and the aortic lesion was repaired. The patient was discharged 6 days after the surgical procedure, in good health. Conclusions We presented a very rare case of late diagnosis of aortic injury caused by a gunshot lesion, in which the particular trajectory of the bullet helped avoid immediate life-threatening bleeding and, probably, saved the patient’s life

Regional Development of Glioblastoma: The Anatomical Conundrum of Cancer Biology and Its Surgical Implication

Glioblastoma (GBM) are among the most common malignant central nervous system (CNS) cancers, they are relatively rare. This evidence suggests that the CNS microenvironment is naturally equipped to control proliferative cells, although, rarely, failure of this system can lead to cancer development. Moreover, the adult CNS is innately non-permissive to glioma cell invasion. Thus, glioma etiology remains largely unknown. In this review, we analyze the anatomical and biological basis of gliomagenesis considering neural stem cells, the spatiotemporal diversity of astrocytes, microglia, neurons and glutamate transporters, extracellular matrix and the peritumoral environment. The precise understanding of subpopulations constituting GBM, particularly astrocytes, is not limited to glioma stem cells (GSC) and could help in the understanding of tumor pathophysiology. The anatomical fingerprint is essential for non-invasive assessment of patients’ prognosis and correct surgical/radiotherapy planning

Regional Development of Glioblastoma: The Anatomical Conundrum of Cancer Biology and Its Surgical Implication

Glioblastoma (GBM) are among the most common malignant central nervous system (CNS) cancers, they are relatively rare. This evidence suggests that the CNS microenvironment is naturally equipped to control proliferative cells, although, rarely, failure of this system can lead to cancer development. Moreover, the adult CNS is innately non-permissive to glioma cell invasion. Thus, glioma etiology remains largely unknown. In this review, we analyze the anatomical and biological basis of gliomagenesis considering neural stem cells, the spatiotemporal diversity of astrocytes, microglia, neurons and glutamate transporters, extracellular matrix and the peritumoral environment. The precise understanding of subpopulations constituting GBM, particularly astrocytes, is not limited to glioma stem cells (GSC) and could help in the understanding of tumor pathophysiology. The anatomical fingerprint is essential for non-invasive assessment of patients’ prognosis and correct surgical/radiotherapy planning