- Franco Grimaldi (DOB 12.10.1951), is the Chief of the Endocrinology, Metabolism and Clinical Nutrition Unit, Univers... moreFranco Grimaldi (DOB 12.10.1951), is the Chief of the Endocrinology, Metabolism and Clinical Nutrition Unit, University Hospital “Santa Maria della Misericordia”, Udine, Italy. He is Professor of Endocrinology at the School of Medicine, Internal Medicine and Surgery (University of Udine). He also served as Professor of Metabolic Diseases, Endocrinology of Physical Exercise at School of Sport Sciences, Endocrinology related to sterility and infertility at School of Specialization in Gynecology and Obstetrics, Endocrinology at School of Specialization in Oncology, Hematology and Dermatology (University of Udine).He is the Past President of the Italian AACE Chapter, member of the Association of Endocrinologists, of the Italian Society of Endocrinology, of the Italian Association for Neuroendocrine Tumours, of the Italian Andrology and Sexuality Medicine, of the Italian Diabetology Society, of the Italian Association of Diabetologists, of the Italian and EuropeanThyroid Association, of the Endocrine Society, of the American Association of Clinical Endocrinologists, of the European Neuroendocrine Tumor Society.Prof. Grimaldi is frequently invited as presenter or docent at Endocrine and Oncological conferences and coursesedit
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Background: In patients with well-differentiated (WD) neuroendocrine tumors (NET), long-acting octreotide (LAR), conventionally administered at a dose of 30 mg every 28 days, has well-documented anti-secretive but limited... more
Background: In patients with well-differentiated (WD) neuroendocrine tumors (NET), long-acting octreotide (LAR), conventionally administered at a dose of 30 mg every 28 days, has well-documented anti-secretive but limited antiproliferative effects. Aim: The objective of this study was to evaluate a different schedule of LAR treatment consistent with a shorter interval between administrations (21 days) in WDNET patients with progressive disease at standard-dose interval. Subjects and methods: Twenty-eight patients followed for diagnosis and therapy of WDNET who had tumor progression during therapy with LAR 30 mg every 28 days were enrolled. Clinical, biological, and objective tumor response was evaluated after LAR 30 mg every 21 days. Time to progression was also evaluated after LAR 30 mg every 21 days and compared to LAR 30 mg every 28 days. Results: The treatment with LAR 30 mg every 21 days resulted in complete and partial control of clinical symptoms in 40% and 60% of cases, respectively. Circulating neuroendocrine markers were significantly decreased in 30% of cases. A stabilization of disease was obtained in 93% and objective response in 7%. The median time to progression was significantly longer by using the shortened interval of LAR administration as compared to the standard one (30 vs 9 months, p<0.0001). The treatment was safe and well tolerated. Conclusions: The shortened schedule of LAR administration was able to re-institute control of clinical symptoms, to decrease level of circulating neuroendocrine markers and to increase time to progression in patients previously escaping from a standard schedule treatment.
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Adrenalectomy represents the gold standard treatment for hyperfunctioning adrenal incidentaloma. In cases of silent adrenal masses, on the other hand, the surgical removal of an adrenocortical cancer entails the sacrifice of a large... more
Adrenalectomy represents the gold standard treatment for hyperfunctioning adrenal incidentaloma. In cases of silent adrenal masses, on the other hand, the surgical removal of an adrenocortical cancer entails the sacrifice of a large number of safe benign masses, and in most cases surgery is therefore unjustified. The aim of this paper was to clarify the surgical indications for adrenal incidentaloma by reviewing our experience in comparison with the main reference literature. Over the period from 1995 to 2001 we managed 40 cases of incidentaloma. US and CT abdominal scans, adrenal scintigraphy and biochemical tests were performed on an outpatient basis. Seven pre-Cushing syndromes were removed. Ten incidentalomas measured 4 cm or more in diameter: 5 of these were operated on and in 5 cases surgery was not feasible or was refused. Only one malignant mass was detected (an angiosarcoma). Four postoperative minimal complications (18.7%) were observed. The follow-up (median: 48 months) was uneventful. The surgical approach was traditional in 11 cases and laparoscopic in 1 case. Surgery should be considered mandatory in cases of hyperfunctioning adrenal masses in the presence of suspect radiological evidence, in cases of discordant CT and scintigraphy findings and when the maximum diameter is 4 cm or more.
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Research Interests: Endocrinology, Gastroenterology, Medicine, Humans, Internal Medicine, and 15 moreFemale, Male, Endocrine, Risk factors, Clinical Sciences, Aged, Middle Aged, Adult, Retrospective Studies, Age Factors, Risk Factors, Neuroendocrine Tumors, Gastrin, Chromogranin A, and Paediatrics and reproductive medicine
IntroductionObesity is a global pandemic and is cause of serious concern in all regions of the world. It is important to raise the attention of health care professionals in order to provide early treatment of patients with obesity.... more
IntroductionObesity is a global pandemic and is cause of serious concern in all regions of the world. It is important to raise the attention of health care professionals in order to provide early treatment of patients with obesity. Obesity management, however, varies greatly amongst endocrinologists with respect to attitudes to diagnosis and treatment. Aim of this study was to identify practices and needs of Italian endocrinologists with respect to people with obesity.MethodsIn this study, all members of the Italian Association of Clinical Endocrinologists (AME) were invited to participate in a web-based survey concerning the management of obesity.ResultsThe response rate was 24.1% (542/2248). Nutritional and obesity problems were reported as major areas of interest by 29.4% of the participants. A large proportion of patients seeking an endocrine consultation for other reasons are affected by obesity, but one in five respondents addressed the issue in 25% or less of the cases, while...
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Aim: This guideline (GL) is aimed at providing a reference for the management of non-functioning, benign thyroid nodules causing local symptoms in adults outside of pregnancy. Methods: This GL has been developed following the methods... more
Aim: This guideline (GL) is aimed at providing a reference for the management of non-functioning, benign thyroid nodules causing local symptoms in adults outside of pregnancy. Methods: This GL has been developed following the methods described in the Manual of the National Guideline System. For each question, the panel appointed by Associazione Medici Endocrinology(AME) identified potentially relevant outcomes, which were then rated for their impact on therapeutic choices. Only outcomes classified as “critical” and “important” were considered in the systematic review of evidence and only those classified as “critical” were considered in the formulation of recommendations. Results: The present GL contains recommendations about the respective roles of surgery and minimally invasive treatments for the management of benign symptomatic thyroid nodules. We suggest hemithyroidectomy plus isthmectomy as the first-choice surgical treatment, provided that clinically significant disease is not...
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Aims: Metformin is the most widely used drug for the first-line treatment of type 2 diabetes mellitus (T2DM), but its use and schedule have been poorly investigated in elderly patients. Methods: We conducted an observational,... more
Aims: Metformin is the most widely used drug for the first-line treatment of type 2 diabetes mellitus (T2DM), but its use and schedule have been poorly investigated in elderly patients. Methods: We conducted an observational, cross-sectional, multicentric study on metformin in T2DM outpatients older than 65 years who were taking the drug for at least 6 months and referred to Italian Endocrinology and Diabetology Services. The primary endpoint was daily metformin dose, and secondary endpoints were the correlations between metformin dose and age, comorbidities, and concomitant use of other drugs. The study was open to all members of AME (Associazione Medici Endocrinologi). Results: Fifteen Italian centers recruited 751 consecutive participants (42.9% older than 75 years, 48.6% females). T2DM duration was 12.9 ± 9.7 years (longer than 10 years in 53.8%). Metformin had been used for 10.3 ± 6.8 years (longer than 10 years in 52.4%). Metformin dose was 1.6 ± 0.9 g/day (>1.5 g/day in 63...
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AKT A protein-serine-threonine kinase that is activated by phosphorylation in response to growth factors or insulin CD117 Antigen specific for the proto-oncogene c-kit CD56 Antigen expressed by all lymphocytes CD99 Cluster of... more
AKT A protein-serine-threonine kinase that is activated by phosphorylation in response to growth factors or insulin CD117 Antigen specific for the proto-oncogene c-kit CD56 Antigen expressed by all lymphocytes CD99 Cluster of differentiation CDX-2 Transcription factor expressed specifically in gut epithelium CEACAM1 Cell adhesion molecule
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The carcinoid syndrome (CS) and hyperinsulinemic hypoglycemia (HH) represent two of the most common clinical syndromes associated with neuroendocrine neoplasms (NENs). The former is mainly related to the serotonin secretion by a small... more
The carcinoid syndrome (CS) and hyperinsulinemic hypoglycemia (HH) represent two of the most common clinical syndromes associated with neuroendocrine neoplasms (NENs). The former is mainly related to the serotonin secretion by a small bowel NEN, whereas the latter depends on an insulin hypersecretion by a pancreatic insulinoma. Both syndromes/conditions can affect prognosis and quality of life of patients with NENs. They are often diagnosed late when patients become strongly symptomatic. Therefore, their early detection and management are a critical step in the clinical management of NEN patients. A dedicated and experienced multidisciplinary team with appropriate therapeutic strategies is needed and should be encouraged to optimize clinical outcomes. This review aims to critically analyze clinical features, evidence and treatment options of CS and HH and therefore to improve their management.
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Background: Metformin is an oral hypoglycemic agent extensively used as first-line therapy for type 2 diabetes. It improves hyperglycemia by suppressing hepatic glucose production and increasing glucose uptake in muscles. Metformin... more
Background: Metformin is an oral hypoglycemic agent extensively used as first-line therapy for type 2 diabetes. It improves hyperglycemia by suppressing hepatic glucose production and increasing glucose uptake in muscles. Metformin improves insulin sensitivity and shows a beneficial effect on weight control. Besides its metabolic positive effects, Metformin has direct effects on inflammation and can have immunomodulatory and antineoplastic properties. Aim: The aim of this narrative review was to summarize the up-to-date evidence from the current literature about the metabolic and non-metabolic effects of Metformin. Methods: We reviewed the current literature dealing with different effects and properties of Metformin and current recommendations about the use of this drug. We identified keywords and MeSH terms in Pubmed and the terms Metformin and type 2 diabetes, type 1 diabetes, pregnancy, heart failure, PCOS, etc, were searched, selecting only significant original articles and revi...
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Introduction: This guideline (GL) is aimed at providing a reference for the management of prolactin (PRL)-secreting pituitary adenoma in adults. However, pregnancy is not considered. Methods: This GL has been developed following the... more
Introduction: This guideline (GL) is aimed at providing a reference for the management of prolactin (PRL)-secreting pituitary adenoma in adults. However, pregnancy is not considered. Methods: This GL has been developed following the methods described in the Manual of the Italian National Guideline System. For each question, the panel appointed by Associazione Medici Endocrinologi (AME) has identified potentially relevant outcomes, which have then been rated for their impact on therapeutic choices. Only outcomes classified as “critical” and “important” have been considered in the systematic review of evidence and only those classified as “critical” have been considered in the formulation of recommendations. Results: The present GL provides recommendations regarding the role of pharmacological and neurosurgical treatment in the management of prolactinomas. We recommend cabergoline (Cab) vs. bromocriptine (Br) as the first-choice pharmacological treatment to be employed at the minimal effective dose capable of achieving the regression of the clinical picture. We suggest that medication and surgery are offered as suitable alternative first-line treatments to patients with non-invasive PRL-secreting adenoma, regardless of size. We suggest Br as an alternative drug in patients who are intolerant to Cab and are not candidates for surgery. We recommend pituitary tumor resection in patients 1) without any significant neuro-ophthalmologic improvement within two weeks from the start of Cab, 2) who are resistant or do not tolerate Cab or other dopamine-agonist drugs (DA), 3) who escape from previous efficacy of DA, and 4) who are unwilling to undergo a chronic DA treatment. We recommend that patients with progressive disease notwithstanding previous tumor resection and ongoing DA should be managed by a multidisciplinary team with specific expertise in pituitary diseases using a multimodal approach that includes repeated surgery, radiotherapy, DA, and possibly, the use of temozolomide. Conclusion: The present GL is directed to endocrinologists, neurosurgeons, and gynecologists working in hospitals, in territorial services or private practice, and to general practitioners and patients.
Introduction: Histological distinction between typical and atypical bronchopulmonary car-cinoids is based on mitotic activity and necrosis. Regardless of these two parameters, outcome after surgery is often unpredictable. In this study... more
Introduction: Histological distinction between typical and atypical bronchopulmonary car-cinoids is based on mitotic activity and necrosis. Regardless of these two parameters, outcome after surgery is often unpredictable. In this study the prognostic value of different clinico-pathological factors was retrospectively analyzed in a large series of patients with bronchopulmonary carcinoid. Materials and Methods: The long-term post-surgical out-
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Background: Medullary thyroid cancer (MTC) accounts for 5% of all thyroid cancers and occurs either sporadically or in a hereditary pattern. Routine calcitonin (CT) measurement is suggested for MTC screening in patients with nodular... more
Background: Medullary thyroid cancer (MTC) accounts for 5% of all thyroid cancers and occurs either sporadically or in a hereditary pattern. Routine calcitonin (CT) measurement is suggested for MTC screening in patients with nodular thyroid disease. Patient Findings: A 45 years-old woman incidentally discovered, with neck ultrasound, the presence of thyroid micronodules. Fine-needle aspiration (FNA) on thyroid prevailing nodule did not demonstrate cellular atypia. During follow-up, FNA was repeated on the previously analyzed nodule suspicious for Hürthle cell nodule suspicious for follicular neoplasm and on another hypoechoic right nodule which showed cellular atypia. CT was <2 pg/ml (normal values <18.2 pg/ml), anti-thyroid antibodies were positive and the patient showed a normal thyroid function. The patient also was diagnosed with primary hyperparathyroidism with an enlarged parathyroid gland behind the right thyroid lobe. Therefore, she underwent total thyroidectomy and a ...
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Introduction Thyroid function tests (TFT) are extensively used in daily clinical practice. Here, we described a case of incongruent TFT both in a pregnant woman and in her newborn. Case presentation A 32-year-old woman, diagnosed with... more
Introduction Thyroid function tests (TFT) are extensively used in daily clinical practice. Here, we described a case of incongruent TFT both in a pregnant woman and in her newborn. Case presentation A 32-year-old woman, diagnosed with autoimmune thyroiditis during her first pregnancy, was monitored during her second gestation. At week 5 + 2 days, thyroid-stimulating hormone (TSH) and free thyroxine (FT4) values (Dimension VISTA 1500, Siemens Healthineers) were within normal limits. At week 19 + 5 days, TSH remained normal while FT4 increased approximately by three-fold. FT4 inconsistency was with both TSH and the clinical status since she continued to be clinically euthyroid. On the same serum sample, thyroid autoantibodies were negative. At week 25 + 4 days, the patient complained of palpitations and dyspnea, with tachycardia. Even though TSH was normal, high levels of both FT4 and free triiodothyronine (FT3) were interpreted as evidence of thyroid overactivity and methimazole was ...
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BACKGROUND AND OBJECTIVE BLyS (B-Lymphocyte stimulator) is over-expressed in several tumoral settings, with direct or indirect effects on neoplastic proliferation and possibly representing a therapeutic target. In this study, we explored... more
BACKGROUND AND OBJECTIVE BLyS (B-Lymphocyte stimulator) is over-expressed in several tumoral settings, with direct or indirect effects on neoplastic proliferation and possibly representing a therapeutic target. In this study, we explored the role of BLyS in a large population of patients with neuroendocrine tumors (NETs). METHODS The study analyzed the stored sera of 124 consecutive unselected patients with NETs: 36 lung carcinoids (24 typical, 12 atypical), 47 gastroenteric tract and 41 pancreatic (30 non-functioning and 11 functioning: 9 insulinomas, 2 glucagonomas). In 23 cases, BLyS was repeatedly assessed during the follow-up and the disease was monitored (progression, stabilization or remission) according to the RECIST criteria. Patients were compared to 92 age and sex-matched blood donors (BDs). Serum levels of BLyS and Chromogranin A (CgA) were analyzed by ELISA. RESULTS NET patients showed significantly higher BLyS levels than BDs (1274±809 pg/ml vs. 587±173 pg/ml; p<0.0001). BLyS correlated weakly with CgA (r=0.19 and p=0.035) but did not correlate with Ki67, grading, metastasis, histological type and site. In patients with sustained remission after surgery, BLyS and CgA both showed a gradual reduction over time. Patients with progressing disease showed higher BLyS levels compared to stable patients (1524±694 pg/ml vs. 1168± 373 pg/ml; p= 0.033). BLyS serum levels remained stable in remission and therapy-controlled patients, while increased in the follow-up of progressing cases. CONCLUSION Higher BLyS levels identify patients with a more severe disease, characterized by progression despite treatments, possibly representing a factor implicated in the proliferation of the neoplastic cells or in sustaining the neoplastic environment.
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L’osteoporosi e le fratture da fragilità scheletrica rappresentano importanti comorbidità nei pazienti con carcinoma differenziato della tiroide (DTC), con potenziale impatto negativo sulla qualità di vita e sulla sopravvivenza. La... more
L’osteoporosi e le fratture da fragilità scheletrica rappresentano importanti comorbidità nei pazienti con carcinoma differenziato della tiroide (DTC), con potenziale impatto negativo sulla qualità di vita e sulla sopravvivenza. La terapia TSH-soppressiva rappresenta il principale determinante della fragilità scheletrica nei pazienti con DTC, favorendo il riassorbimento osseo e il deterioramento della microstruttura ossea. Tale effetto negativo può essere amplificato in presenza di metastasi ossee che incrementano ulteriormente il rischio di fratture. L’inquadramento e la gestione della fragilità scheletrica nel DTC sono ancora controverse e i dati sull’efficacia dei farmaci osteo-attivi in questo contesto clinico sono scarsi.
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1604 Background: The clinical behavior of neuroendocrine tumors (NET) is highly variable, but the only data available in literature on large series are mainly based on retrospective register data collected in 3-5 decades, focusing on... more
1604 Background: The clinical behavior of neuroendocrine tumors (NET) is highly variable, but the only data available in literature on large series are mainly based on retrospective register data collected in 3-5 decades, focusing on short-term follow-up. These are clearly insufficient due to the frequent evolution in classification criteria, diagnostic techniques and the scarcity of clinical data. Methods: Data from a total of 1659 NET patient were collected from 12 Italian referral centers. A specific software was developed for the study. Only patients with histological diagnosis revised according to the WHO Classification in active long term follow-up in the period 1990-2010 were included in the study. Patients with incomplete diagnostic work-up, without clinical data or lost at follow-up were excluded. Cumulative survival were analyzed according to site of origin, histotype, grading, ki67 score, secreting pattern (functioning or not functioning) and staging. Results: At 2 yr cum...
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Research Interests: Calcium, Medicine, Italy, Humans, Female, and 15 moreMale, Clinical Sciences, Aged, Middle Aged, Time Factors, Retrospective Studies, Hyperparathyroidism, Primary hyperparathyroidism, Clinical Endocrinology, Gastrointestinal Diseases, Parathyroidectomy, Secondary Hyperparathyroidism, hypocalcemia, Paediatrics and reproductive medicine, and Cinacalcet
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Purpose Reliable cut-offs for basal (bCT) and calcium stimulated calcitonin (casCT) are needed for an early and accurate diagnosis of medullary thyroid cancer (MTC). Patients and methods Fifty-four new patients with nodular goiter were... more
Purpose Reliable cut-offs for basal (bCT) and calcium stimulated calcitonin (casCT) are needed for an early and accurate diagnosis of medullary thyroid cancer (MTC). Patients and methods Fifty-four new patients with nodular goiter were enrolled and analysed together with those previously published by our group for a total of 135 cases. bCT and casCT were measured by a highly sensitive method and the results compared with histological findings. In a subgroup of patients, cardiac rhythm was recorded before and during the calcium test. Results In both females (F) and males (M), there was a significant correlation between tumor size and bCT levels (P 30 (F) and > 34 pg/mL (M), whereas the best casCT thresholds were > 79 (F) and > 466 pg/mL (M). bCT was shown to harbour a high accuracy, though some cases were diagnosed only upon stimulation test. Importantly, combining bCT, below or above the cut-offs, with casCT above the cut-offs, all the MTC cases were correctly identified. ...
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Neuroendocrine tumors (NETs) can produce hormones or peptides that cause specific clinical syndromes.
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The advent of highly active antiretroviral therapy (HAART) has significantly improved the survival of people living with human immunodeficiency virus (HIV) infection [1].
Aims: The aim of this study was to investigate the epidemiology of histology-proven Neuroendocrine neoplasms (NENs) in an Italian area. Background: NENs are a rare and poorly known disease and the global incidence and prevalence appears... more
Aims: The aim of this study was to investigate the epidemiology of histology-proven Neuroendocrine neoplasms (NENs) in an Italian area. Background: NENs are a rare and poorly known disease and the global incidence and prevalence appears to be increasing over the past decades. Objective: The objectives of this study were to estimate the incidence and trends of NENs in a 250,000-inhabitant area in the North-East of Italy in the 1998-2018 period and to compare them with international data. Methods: This retrospective cohort study was based on the analysis of anonymous health administrative databases, linked with each other at the individual patient level through an anonymous stochastic key. NENs were identified from the anatomical pathology database. The standardized incidence rate (2010ESP and US2000) ± 95% CI per 100,000 were calculated, both annually and globally for the whole period. Incidence was also calculated for specific anatomical sites and by sex. Trends for the considered p...
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Background and Objectives: This observational study aims to determine the correlation between glycemic control with the HbA1c value and adverse obstetric outcome in women affected by pre-gestational diabetes. Materials and Methods: A... more
Background and Objectives: This observational study aims to determine the correlation between glycemic control with the HbA1c value and adverse obstetric outcome in women affected by pre-gestational diabetes. Materials and Methods: A retrospective analysis has been performed at the University Hospital of Udine. Only patients with a singleton pregnancy, pre-gestational diabetes, and known level of Hb A1c throughout pregnancy were included in the study. Results: According to the HbA1c level, at the beginning of pregnancy, 49 patients with HbA1c ≤ 7.0% were compared with 45 patients with HbA1c > 7.0%. Maternal age at diagnosis of the disease was significantly higher in the group with HbA1c ≤ 7% than in the group with HbA1c > 7%, 26.00 (18.00–32.00) vs. 20.00 (12.50–27.00). Women with HbA1c ≤ 7.0% reached, at term of pregnancy, significantly lower levels of HbA1c, 5.8% (5.7–6.0) vs. 6.7% (6.3–7.3). Daily insulin units were statistically different between the two groups at the end ...
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e19038 Background: MCC is a rare cutaneous neuroendocrine neoplasm characterized by an aggressive behavior and a high recurrence rate, generally associated with poor prognosis. Nodal and distant metastases are frequent. Aim of this study... more
e19038 Background: MCC is a rare cutaneous neuroendocrine neoplasm characterized by an aggressive behavior and a high recurrence rate, generally associated with poor prognosis. Nodal and distant metastases are frequent. Aim of this study was to report histological, clinical and prognostic features of a series of 12 patients with nodal MCC in the lack of evidence of a primary. Methods: The cases were collected from a multicentric database: mean age at diagnosis was 67 years; F:M ratio was 1:1.4; mean follow up was 54 months (8-108). Involved nodal sites were: inguinal (9) and axillar (3). All cases had typical MCC immunoprofile: neuroendocrine (CgA, NSE, Syn) and epithelial (CK 20 dot-like) marker positivity. Complete and extensive clinical, dermatologic, radiologic and endoscopic work-up was performed. All patients underwent surgical excision; in one case chemotherapy, in another case biotherapy and in one further case radiotherapy was administered. Results: All cases were in stage ...
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Background. The KEAP1/NRF2 pathway has been widely investigated in tumors since it was implicated in cancer cells survival and therapies resistance. In lung tumors the deregulation of this pathway is mainly related to point mutations of... more
Background. The KEAP1/NRF2 pathway has been widely investigated in tumors since it was implicated in cancer cells survival and therapies resistance. In lung tumors the deregulation of this pathway is mainly related to point mutations of KEAP1 and NFE2L2 genes and KEAP1 promoter hypermethylation, but these two genes have been rarely investigated in low/intermediate grade neuroendocrine tumors of the lung. Methods. The effects of KEAP1 silencing on NRF2 activity was investigated in H720 and H727 carcinoid cell lines and results were compared with those obtained by molecular profiling of KEAP1 and NFE2L2 in a collection of 47 lung carcinoids. The correlation between methylation and transcript levels was assessed by 5-aza-dC treatment. Results. We demonstrated that in carcinoid cell lines, the KEAP1 silencing induces an upregulation of NRF2 and some of its targets and that there is a direct correlation between KEAP1 methylation and its mRNA levels. A KEAP1 hypermethylation and Loss of H...