When Should We Adopt EUS-Guided Radiofrequency Ablation in Pancreatic Neuroendocrine Tumors?

Pancreatic neuroendocrine neoplasms (PanNENs) are rare and heterogeneous diseases that account for less than 2% of all cases of pancreatic cancer and only 30% of digestive neuroendocrine neoplasia, even if their incidence and prevalence continue to rise globally [...]

Management of functional pancreatic neuroendocrine neoplasms

: Functional pancreatic neuroendocrine neoplasms (pNENs) are rare and heterogeneous diseases in terms of both clinical and pathological aspects. These tumors secrete hormones or peptides, which may cause a wide variety of symptoms related to a clinical syndrome. The management of functional pNENs is still challenging for clinicians due to the need to control both tumor growth and specific symptoms. Surgery remains the cornerstone in the management of local disease because it can definitively cure the patient. However, when the disease is not resectable, a broad spectrum of therapeutic options, including locoregional therapy, somatostatin analogs (SSAs), targeted therapies, peptide-receptor radionuclide therapy (PRRT), and chemotherapy, are available. The present review summarizes the main key issues regarding the clinical management of these tumors, providing a specific highlight on their therapeutic approach

Glomerular and mitral-granule cell microcircuits coordinate temporal and spatial information processing in the olfactory bulb

The olfactory bulb processes inputs from olfactory receptor neurons (ORNs) through two levels: the glomerular layer at the site of input, and the granule cell level at the site of output to the olfactory cortex. The sequence of action of these two levels has not yet been examined. We analyze this issue using a novel computational framework that is scaled up, in three-dimensions (3D), with realistic representations of the interactions between layers, activated by simulated natural odors, and constrained by experimental and theoretical analyses. We suggest that the postulated functions of glomerular circuits have as their primary role transforming a complex and disorganized input into a contrast-enhanced and normalized representation, but cannot provide for synchronization of the distributed glomerular outputs. By contrast, at the granule cell layer, the dendrodendritic interactions mediate temporal decorrelation, which we show is dependent on the preceding contrast enhancement by the glomerular layer. The results provide the first insights into the successive operations in the olfactory bulb, and demonstrate the significance of the modular organization around glomeruli. This layered organization is especially important for natural odor inputs, because they activate many overlapping glomeruli

Utility of histopathological revision in the management of gastro-entero-pancreatic neuroendocrine neoplasia

Background: Histological evaluation and grading assessment are key points in the diagnostic work-up of gastroentero-pancreatic neuroendocrine neoplasms (GEP-NENs). Aim: To analyze the impact of histopathological revision on the clinical management of patients with GEP-NEN. Materials and methods: Patients referred to our Center of Excellence between 2015 and 2021 were included in this study. Immunohistochemical slides at the time of initial diagnosis were reviewed to assess tumor morphology, diagnostic immunohistochemistry, and Ki67. Results: 101 patients were evaluated, with 65 (64.4%) gastrointestinal, 25 (24.7%) pancreatic, and 11 (10.9%) occult neoplastic lesions suspected to be of GEP origin. The main changes resulting from the revision were: first Ki-67 assessment in 15.8% of patients, Ki-67 change in 59.2% of patients and grading modification in 23.5% of patients. An additional immunohistochemical evaluation was performed in 78 (77.2%) patients, leading to a confirmation of GEP origin in 10 of 11 (90.9%) of unknown primary site neoplastic lesions and an exclusion of NEN diagnosis in 2 (2%) patients. After histopathological revision, a significant modification in clinical management was proposed in 42 (41.6%) patients. Conclusions: Histopathological revision in a referral NEN center is strongly advised in newly diagnosed GEP-NENs to properly plan prognostic stratification and therapeutic choice

Improving of psychological status and inflammatory biomarkers during omalizumab for chronic spontaneous urticaria

Background: Depression and anxiety are the most common psychiatric comorbidities in chronic spontaneous urticaria (CSU). Omalizumab is a monoclonal antibody approved for CSU treatment. We evaluated the prevalence of anxiety and depression in CSU patients before and after treatment with omalizumab. Materials & methods: A total of 30 patients were enrolled in the study: 15 patients affected by CSU and treated with omalizumab and the other 15 healthy subjects did not receive any systemic therapy. All patients were evaluated using Hospital Anxiety and Depression Scale, CRP and erythrocyte sedimentation rate, at baseline and after 6 months. Results: The omalizumab group after 6 months of therapy had a decrease of all the scores and biomarkers. Conclusion: Omalizumab allowed an improvement of urticaria and mental comorbidities

Ruthenium complexes bearing glucosyl ligands are able to inhibit the amyloid aggregation of short Histidine-peptides

Neurodegenerative diseases are often characterized by the formation of aggregates of amyloidogenic peptides and proteins, facilitating the formation of neurofibrillary plaques. In this study, we investigate a series of Ru-complexes sharing three-legged piano-stool structures based on the arene ring and glucosylated carbene ligands. The ability of these complexes to bind amyloid His-peptides was evaluated by ESI-MS, and their effects on the aggregation process were investigated through ThT and Tyr fluorescence emission. The complexes were demonstrated to bind the amyloidogenic peptides even with different mechanisms and kinetics depending on the chemical nature of the ligands around the Ru(II) ion. TEM analysis detected the disaggregation of typical fibers caused by the presence of Ru-compounds. Overall, our results show that the Ru-complexes can modulate the aggregation of His-amyloids and can be conceived as good lead compounds in the field of novel anti-aggregating agents in neurodegeneration

Liver Stiffness Measurement Allows Early Diagnosis of Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome in Adult Patients Who Undergo Hematopoietic Stem Cell Transplantation: Results from a Monocentric Prospective Study

ABSTRACT Veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), is a life-threatening complication affecting patients undergoing hematopoietic stem cell transplantation (HSCT). The survival rate is higher when specific therapy is initiated early; thus, improving early, noninvasive diagnosis of VOD/SOS is an important need. In an adult population undergoing HSCT, we aimed to assess the role of liver stiffness measurement (LSM), evaluated by transient elastography (TE), for diagnosing VOD/SOS. Between April 2016 and March 2018, 78 consecutive adult patients with indications for allogeneic HSCT were prospectively included. LSM was performed before HSCT and at days +9/10, +15/17, and +22/24 post-HSCT. New European Society for Blood and Marrow Transplantation criteria were used to establish VOD/SOS diagnosis. Four patients developed VOD/SOS (5.1%) during the study period, with a median time of +17 days post-HSCT. A sudden increase in LSM compared with previously assessed values and pre-HSCT values, was seen in all patients who developed VOD/SOS. LSM increases occurred from 2 to 12 days before clinical SOS/VOD appearance. The VOD/SOS diagnostic performance of increased LSM over pre-HSCT assessment showed an area under the receiver operating characteristic curve of 0.997 (sensitivity 75%; specificity 98.7%). LSM gradually decreased following successful VOD/SOS-specific treatment. Interestingly, LSM values did not increase significantly in patients experiencing hepatobiliary complications (according to the Common Terminology Criteria) other than VOD/SOS. LSM by TE can be considered a promising method to perform an early, preclinical diagnosis and follow-up of VOD/SOS

Inability to perform maximal stair climbing test before lung resection: a propensity score analysis on early outcome

Abstract Objective: The objective of the present study was to assess whether patients unable to perform a preoperative maximal stair climbing test had an increased incidence of morbidity and mortality after major lung resection compared to patients who were able to exercise. Methods: Three hundred and ninety one patients submitted to pulmonary lobectomy or pneumonectomy for lung cancer were analyzed. Forty-five of these patients were unable to perform a preoperative maximal stair climbing test for underlying comorbidities. Unadjusted and propensity score case matched comparisons were performed between patients who could and who could not perform a preoperative stair climbing test. Multivariable analyses were then performed to identify predictors of morbidity and mortality, and were validated by bootstrap bagging. Results: Patients who could not perform the stair climbing test had similar morbidity rates (31.1 vs. 35.6%, respectively, PZ0.7), but higher mortality rates (15.6 vs. 4.4%, respectively, PZ0.08) and deaths among complicated patients (50 vs. 12.5%, respectively, PZ0.025), compared to propensity score matched patients who could perform the stair climbing test. Logistic regression analyses showed that the inability to perform the stair climbing test was an independent and reliable predictor of mortality (PZ0.005) but not of morbidity (PZ0.2). Conclusions: Patients unable to perform a preoperative maximal exercise test had an increased risk of mortality after major lung resection. Half of these patients did not survive postoperative complications, due to their decreased aerobic reserve caused by physical inactivity which made them unable to cope with the increased oxygen demand.