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A Angeli

Publications and source records attributed to A Angeli.

At least 55 records · Page 3Linked to original sources
PubMed2001

Galectin-3 as a presurgical immunocytodiagnostic marker of minimally invasive follicular thyroid carcinoma.

Thyroid nodules are a common occurrence in the general population, but only a small number of them are eventually diagnosed as cancers. Fine-needle aspiration biopsy (FNAB) is the most accurate and cost-effective method for the presurgical management of thyroid nodules, but it misses the differential diagnosis between thyroid follicular adenomas and follicular carcinomas. Among them, minimally invasive follicular carcinoma (MIC), also defined as encapsulated tumor, only differs from follicular adenoma for the exhibition of minimal, but entire thickness, infiltration of the capsule and/or vascular invasion. This feature cannot be assessed in FNAB and can occasionally be hard to recognize in surgical specimens. As reported in several studies, galectin-3 is a reliable marker of thyroid malignancy, but no data are available on MICs. We analyzed the immunohistochemical expression of galectin-3 in 17 MICs and 52 follicular adenomas in both preoperative paraffin-embedded cytological human thyroid sediments (cell blocks) obtained by FNAB and in the corresponding surgical specimens. Among the MICs, all surgical samples showed galectin-3 immunoreactivity in the cytoplasm, whereas 16 of 17 corresponding FNAB cell blocks were positive. No evidence of cytoplasmic galectin-3 expression was observed in 48 of 52 adenomas in both cell blocks and histological tissues. These findings indicate that galectin-3 is a reliable presurgical molecular marker of MIC, improving the accuracy of conventional FNAB. It also proves to be useful in the histopathological assessment of resected tumors having suspected malignant features.

Adenoma↗
PubMed2001

Guidelines for diagnosis and therapy of MEN type 1 and type 2.

This is a consensus statement from an international group, mostly of clinical endocrinologists. MEN1 and MEN2 are hereditary cancer syndromes. The commonest tumors secrete PTH or gastrin in MEN1, and calcitonin or catecholamines in MEN2. Management strategies improved after the discoveries of their genes. MEN1 has no clear syndromic variants. Tumor monitoring in MEN1 carriers includes biochemical tests yearly and imaging tests less often. Neck surgery includes subtotal or total parathyroidectomy, parathyroid cryopreservation, and thymectomy. Proton pump inhibitors or somatostatin analogs are the main management for oversecretion of entero-pancreatic hormones, except insulin. The roles for surgery of most entero-pancreatic tumors present several controversies: exclusion of most operations on gastrinomas and indications for surgery on other tumors. Each MEN1 family probably has an inactivating MEN1 germline mutation. Testing for a germline MEN1 mutation gives useful information, but rarely mandates an intervention. The most distinctive MEN2 variants are MEN2A, MEN2B, and familial medullary thyroid cancer (MTC). They vary in aggressiveness of MTC and spectrum of disturbed organs. Mortality in MEN2 is greater from MTC than from pheochromocytoma. Thyroidectomy, during childhood if possible, is the goal in all MEN2 carriers to prevent or cure MTC. Each MEN2 index case probably has an activating germline RET mutation. RET testing has replaced calcitonin testing to diagnose the MEN2 carrier state. The specific RET codon mutation correlates with the MEN2 syndromic variant, the age of onset of MTC, and the aggressiveness of MTC; consequently, that mutation should guide major management decisions, such as whether and when to perform thyroidectomy.

Humans↗
PubMed2001

The patients with incidentally discovered adrenal adenoma (incidentaloma) are not at increased risk of osteoporosis.

The main problem in the management of the patients with incidentally discovered adrenal mass (incidentaloma) is whether and when the incidental mass puts the patient at increased risk for an adverse outcome. As osteoporosis is a well known complication of endogenous and exogenous glucocorticoid excess, it is likely that patients with incidentally discovered adrenocortical adenomas have impaired bone mass due to subclinical hypercortisolism. We measured spinal bone mineral density (BMD) by dual energy x-ray absorptiometry in 27 patients (9 men and 18 women) and 54 healthy subjects (18 men and 36 women) carefully matched for age, sex, body mass index, and menstrual status for a case-control analysis. BMD was also measured at the hip in the group of patients. A multiple regression analysis was performed to determine which biochemical variables might influence BMD values. Lumbar BMD values in patients with adrenal incidentaloma were not significantly different from those in control subjects (BMD, 0.926, 0.604--1.144 vs. 0.936, 0.645--1.268 g/cm(2); P = NS). No significant difference in lumbar and femoral BMD was found between patients with or without subclinical Cushing's syndrome. Among the variables processed, only PTH remained in the final model and was inversely correlated with lumbar spine and femoral neck BMD values (r = -0.5; r(2) = 0.25; P = 0.015 and r = -0.42; r(2) = 0.18; P = 0.03, respectively). In conclusion, our data do not suggest that the slight glucocorticoid excess associated with adrenal incidentaloma increases the risk of osteoporosis. The evaluation of BMD does not seem to be crucial in the management of incidentally discovered adrenal masses.

Absorptiometry, Photon↗
PubMed2001

Treatment of medullary thyroid carcinoma: an update.

Prognosis and treatment effectiveness of medullary thyroid carcinoma (MTC) are largely related to the tumour stage, so that early diagnosis represents an important goal for the management of patients. Recent advances in genetic testing have improved the clinical approach to the familial MTC syndromes. There is general agreement that the primary operation for MTC should obtain the complete removal of the neoplastic tissue in the neck, because any adjuvant treatment has never been proven to be effective. The management of residual/recurrent or metastatic MTC still remains controversial, although a multimodal approach to advanced disease may be of value in palliation or local control of tumour progression. The role of surgery, external radiotherapy, radionuclide therapy and medical treatment, including biological response modifiers and cytotoxic drugs, are reviewed and discussed.

Adult↗
PubMed2001

Metabolic bone disease induced by prostate cancer: rationale for the use of bisphosphonates.

PURPOSE: Increasing evidences indicate that despite the osteoblastic nature of metastatic bone lesions due to prostate cancer osteolysis is a regular feature and may cause skeletal morbidity. This observation provides the rationale for the use of bisphosphonates for managing bone metastatic prostate cancer. MATERIALS AND METHODS: We reviewed the literature on the mechanisms by which prostate cancer affects bone cell function and disrupts physiological bone turnover. We also summarized the clinical results of bisphosphonate for treating bone pain in patients with prostate cancer. RESULTS: Metastatic prostate cancer in bone interferes with physiological bone remodeling by abnormal release of the hormones and paracrine factors physiologically involved in the modulation of osteoblastic and osteoclastic activity. Tumor induced bone formation and resorption develop within the same metastasis but excessive new bone is deposited away from bone resorption sites and does not contribute to bone strength. The increase in bone resorption may also be a generalized phenomenon that is most likely due to iatrogenic osteoporosis or related to hyperparathyroidism in response to the increased calcium demand. The bone resorption index in patients with bone metastatic prostate cancer correlates with bone pain and is an independent predictor of adverse skeletal events. However, small clinical studies of the efficacy of bisphosphonates for controlling bone pain in patients with prostate cancer show contradictory results. CONCLUSIONS: Improved understanding of the pathophysiology of prostate cancer induced metabolic bone disease implies that bisphosphonates may have a role in the treatment of this disorder. This issue is being addressed by large-scale ongoing randomized studies.

Bone Neoplasms↗
PubMed2000

Circulating neuroendocrine markers in patients with prostate carcinoma.

BACKGROUND: Circulating neuroendocrine markers were measured in patients with prostate carcinoma (PC), prostatic intraepithelial neoplasia (PIN), and benign prostatic hypertrophy (BPH) with the goal to: 1) evaluate the differences in the expression of these markers in patients with benign, premalignant, and primary or metastatic PC; 2) evaluate their prognostic significance; 3) compare values in patients with hormone-naive and hormone-refractory disease; and 4) assess changes after androgen deprivation or chemotherapy. METHODS: Serum neuron specific enolase (NSE) (immunoradiometric assay) and plasma chromogranin A (CgA) (enzyme-linked immunoadsorbent assay) were evaluated in 141 patients with BPH, 54 patients with PIN, and 159 patients with PC; 119 patients were bearing hormone-naive disease and 40 were bearing hormone-refractory disease. CgA was monitored in 31 patients submitted to androgen deprivation and in 24 patients receiving chemotherapy. RESULTS: Supranormal CgA was observed more frequently in patients with American Urologic Association (AUA) Stage D2 disease (45.5%) compared with those with Stage D1 disease (33.3%), Stage C disease (16.7%), Stage A/B disease (18.8%), PIN (25.9%), and BPH (17.0%) (P < 0.02). Supranormal NSE did not change in any of the patient subgroups. Elevated CgA was observed in 36.0% of patients with metastases who had hormone-naive disease and in 45.0% of patients with hormone-refractory disease (P value not significant). Supranormal NSE and CgA values were predictors for poor prognosis in patients with hormone-refractory disease. Elevated baseline CgA values decreased > 50% in 1 of 12 patients who received luteinizing hormone-releasing hormone analogs and in 2 of 12 patients who underwent chemotherapy. CONCLUSIONS: CgA appears to reflect the neuroendocrine activity of PC better than NSE. Elevated CgA values correlate with poor prognosis and are scarcely influenced by either endocrine therapy or chemotherapy.

Aged↗
PubMed2000

Interleukin-6 upregulates glucocorticoid receptor numbers in human osteoblast-like cells.

Interactions between the endocrine and immune systems are well known with special regard to the hypothalamic-pituitary-adrenal axis. Little of the literature focuses on the complex effects of cytokines on tissue responsiveness to glucocorticoids (GC). In bone tissue, osteoblasts represent a valuable model for studying GC-cytokine interactions. Hence, we have studied two human osteosarcoma cell lines (Saos-2 and MG-63) with different degrees of differentiation and different constitutive IL-6 production (3.4 +/- 0.3 (mean +/- SE) and 3309 +/- 578 pg/10(6) cells). We measured glucocorticoid receptor (GR) number and affinity as a function of the exposure of cells to different amounts of IL-6. Incubation for 20 h with IL-6 at increasing concentrations up to 2000 pg/ml yielded a significant increase of GR binding sites in both cell lines. IL-6 was also able to reverse the inhibitory effect of dexamethasone (1 mumol/l) on GR in both cell lines. In MG-63 cells, expressing higher concentrations of GR, IL-6 deprivation via a specific anti-IL-6 antibody (100 ng/ml) significantly decreased GR. In Saos-2 cells, expressing lower concentrations of GR, a 40 h treatment with human IL-1 beta (10 ng/ml) significantly increased both IL-6 production and GR. This latter effect was completely abolished by co-treating the cells with the anti-IL-6 antibody. Our results provide evidence that IL-6 is an autocrine positive modulator of GR number in human osteoblasts.

Bone Neoplasms↗
PubMed2000

A survey on adrenal incidentaloma in Italy. Study Group on Adrenal Tumors of the Italian Society of Endocrinology.

The aim of this study was to perform a national survey on occasionally discovered adrenal masses [adrenal incidentalomas (AI)] under the auspices of the Italian Society of Endocrinology. This multicentric and retrospective evaluation of patients with AI includes 1096 cases collected in 26 centers between 1980 and 1995. Relevant information was obtained by means of a specifically tailored questionnaire. Of the 1096 forms received, 1004 were retained for final analysis. Patients were 420 males and 584 females, aged between 15-86 yr (median, 58 yr). Mass size (computed tomography measurement) ranged from 0.5-25 cm (median, 3.0 cm). Hormonal work-up demonstrated that 85% of the masses were nonhypersecretory, 9.2% were defined as subclinical Cushing's syndrome, 4.2% were pheochromocytomas, and 1.6% were aldosteronomas. Adrenalectomy was performed in 380 patients with removal of 198 cortical adenomas (52%), 47 cortical carcinomas (12%), 42 pheochromocytomas (11%), and other less frequent tumor types. Patients with carcinoma were significantly younger than patients with adenoma (median, 46; range, 17-84; vs. 57, 16-83 yr; P = 0.05). Adenomas were significantly smaller than carcinomas (3.5, 1-15 vs. 7.5, 2.6-25 cm; P < 0.001), and a cut-off at 4.0 cm had the highest sensitivity (93%) in differentiating between benign and malignant tumors. Hormonal work-up of patients with subclinical Cushing's syndrome showed low baseline ACTH in 79%, cortisol unsuppressibility after 1 mg dexamethasone in 73%, above normal urinary free cortisol in 75%, disturbed cortisol rhythm in 43%, and blunted ACTH response to CRH in 55%. Only 43% of patients with pheochromocytoma were hypertensive, and 86% showed elevated urinary catecholamines. All patients with aldosteronoma were hypertensive and had suppressed upright PRA. These results indicate that mass size is the most reliable variable in separating benign from malignant AI. Adrenalectomy should be recommended for AI greater than 4.0 cm because of the increased risk of malignancy, especially in young patients. Endocrine evaluation should be performed in all patients to identify silent states of hormone excess.

Adolescent↗
PubMed2000

Growth hormone (GH) responses to GH-releasing hormone alone or combined with arginine in patients with adrenal incidentaloma: evidence for enhanced somatostatinergic tone.

Spontaneous and stimulated GH secretion is blunted in hypercortisolemic states due to increased hypothalamic somatostatinergic tone. However, no data are available on the characteristics of GH secretion in patients with incidentally discovered adrenal adenomas. They represent an interesting model for studying GH secretion, as a slight degree of cortisol excess may frequently be observed in such patients who do not present with any clear Cushingoid sign. In the present study, 10 patients (3 men and 7 women, aged 48-63 yr) with an adrenal mass discovered serendipitously underwent, on separate occasions, a GHRH injection alone or combined with an infusion of the functional somatostatin antagonist, arginine. Thirteen age-matched healthy volunteers served as controls. Briefly, arginine (30 g) was infused from -30 to 0 min, and GHRH (100 microg) was injected as a bolus at 0 min, with measurement of serum GH [immunoradiometric assay (IRMA)] every 15 min for 150 min. Plasma IGF-I (RIA after acid-ethanol extraction) was measured in a morning sample. The diagnosis of cortical adenoma was based on computed tomography features and pattern of uptake on adrenal scintigraphy. Patients with obesity and/or diabetes were excluded. The study design included also an endocrine work-up aimed to study the hypothalamic-pituitary-adrenal axis [urinary free cortisol (UFC) excretion, serum cortisol at 0800 h, plasma ACTH at 0800 h, morning cortisol after overnight 1 mg dexamethasone]. Five of 10 patients showed abnormalities of the hypothalamic-pituitary-adrenal axis, including borderline or increased UFC excretion in 4 of them accompanied by blunted ACTH in 2 cases and failure of cortisol to suppress after dexamethasone in 1; the fifth patient displayed low ACTH and resistance to dexamethasone suppression. However, all patients had a unilateral uptake of the tracer on the side of the mass with suppression of the contralateral normal adrenal gland. As a group, the patients displayed greater UFC excretion and lower ACTH concentrations than the controls. GH release after GHRH treatment was blunted in patients bearing adrenal incidentaloma compared with controls (GH peak, 5.7 +/- 5.2 vs. 18.0 +/- 7.0 microg/L; P < 0.0001), whereas GHRH plus arginine was able to elicit a comparable response in the 2 groups (GH peak, 33.5 +/- 20.3 vs. 33.7 +/- 17.5 microg/L; P = NS). The ratio between GH peaks after GHRH plus arginine and after GHRH plus saline was significantly greater in patients than in controls (751 +/- 531% vs. 81 +/- 45%; P = 0.0001). Similar data were obtained when comparing GH area under the curve after GHRH plus saline or GHRH plus arginine between the 2 groups. In summary, the present data suggest that in patients with incidental adrenal adenomas the GH response to GHRH is blunted due to increased somatostatinergic tone, as it can be restored to normal by pretreatment with the functional somatostatin antagonist arginine. The blunted GH release to GHRH may be an early and long lasting sign of autonomous cortisol secretion by the adrenal adenoma.

Adenoma↗
PubMed2000

Low-dose monitored mitotane treatment achieves the therapeutic range with manageable side effects in patients with adrenocortical cancer.

Eight patients with adrenocortical cancer were treated with low doses of mitotane (2-3 g daily) while monitoring drug plasma levels. When the mitotane concentrations reached the therapeutic range (defined as mitotane plasma levels between 14-20 microg/mL), a dose reduction was performed to avoid toxicity. Thereafter, the mitotane dose was tailored according to plasma levels. A progressive increase in plasma mitotane concentrations was observed during treatment, and a highly significant linear correlation was found between plasma drug levels and the total mitotane dose. The therapeutic threshold was reached in all patients after 3-5 months and a total mitotane dose of 283-387 g/days (median, 363). The duration of treatment was 8-40 months (median, 9). Toxicity was manageable in all but one patient, who discontinued treatment. It is therefore possible to design a standard low dose schedule, e.g. 3 g/daily for about 3-4 months with following dose adjustments guided by the monitoring of plasma mitotane levels. This approach is able to provide therapeutic mitotane concentrations and limit the unwanted effects. The present data provide a rationale to change the approach to mitotane treatment in patients with adrenocortical carcinoma from high dose to low dose regimens.

Adrenal Cortex Neoplasms↗
PubMed2000

The value of dehydroepiandrosterone sulfate measurement in the differentiation between benign and malignant adrenal masses.

OBJECTIVE: Owing to their increasing rate of discovery as incidental findings, the characterization of adrenal masses is an important diagnostic problem which frequently challenges the clinician's skill. DESIGN: The results of dehydroepiandrosterone sulfate (DHEAS) measurement were evaluated in a consecutive series of 107 patients with an adrenal mass (39 men, 68 women aged 15-81 years, median 56 years). DHEAS levels observed in the patients were categorized as reduced, normal or elevated according to sex- and age-adjusted reference ranges obtained by measuring DHEAS in 214 healthy women and 142 healthy men aged 17-93 years. The working hypothesis was that a low DHEAS level is a marker of benignity. METHODS: In 84 patients, the adrenal mass was discovered serendipitously, while in the remainder the mass was clinically symptomatic. Patients with known extra-adrenal malignancies were excluded. The adrenal masses were categorized as benign or malignant by computerized tomography (CT) criteria. All patients with suspected malignant tumors or with overtly hypersecreting tumors underwent adrenalectomy. The patients with a presumptive benign tumor were followed-up for at least 12 months. RESULTS: In the overall series, the sensitivity and specificity of a low DHEAS level in the identification of a benign lesion were 41% and 100% respectively. Superimposable figures were obtained when considering only adrenal incidentalomas. DHEAS levels in adrenal cancers displayed some overlap with adrenal adenomas, but in only 2/11 adrenal cancers were DHEAS levels normal, while they were elevated in the remainder. CONCLUSIONS: The present data suggest that DHEAS measurement may help to differentiate benign from malignant adrenal masses as a complementary test of CT in a clinical research setting. The value of DHEAS measurement in general practice is limited because it may be difficult to differentiate between low and low-normal values, particularly in the elderly.

Adolescent↗
PubMed2000

Incidence of skeletal complications in patients with bone metastatic prostate cancer and hormone refractory disease: predictive role of bone resorption and formation markers evaluated at baseline.

PURPOSE: We evaluated the incidence of skeletal complications in patients with bone metastatic prostate cancer and hormone refractory disease. We also assessed the predictive role of bone turnover markers determined at baseline. MATERIALS AND METHODS: A total of 112 patients were consecutively enrolled in our study from July 1990 to July 1998 and followed until death or the last followup. Bone pain, disease extent in bone, serum prostate specific antigen, hemoglobin, and a panel of bone formation and resorption markers were assessed at baseline before any second line treatment. RESULTS: Skeletal complications in 34 patients (30.3%, estimated yearly incidence 12.3%) involved vertebral deformity or collapse requiring spinal orthosis in 20 (17.9%), spinal cord compression in 7 (6.2%), pathological bone fracture in 10 (8.9%), symptomatic hypercalcemia in 1 (0.9%) and symptomatic hypocalcemia in 1 (0.9%). Median time to the evidence of the initial skeletal complication was 9.5 months. These adverse events did not influence overall survival. At baseline patients with eventual skeletal complications had greater bone pain (p = 0.02), a heavier tumor load in bone (p = 0.005), lower performance status (p = 0.05), and higher serum alkaline phosphatase (p <0.02) and urinary deoxypyridoline (p <0.05) than their counterparts. Multivariate analysis revealed that only urinary deoxypyridinoline was independently associated with the onset of these events (p <0.02). The scatterplot of urinary deoxypyridinoline values in patients with and without skeletal complications enabled us to detect a cutoff of 38 pM./mM. for predicting 51% of skeletal events with only an 8% false-positive rate. CONCLUSIONS: Skeletal complications are common in patients with prostate cancer and hormone refractory disease. Bone loss is the major cause of onset. Baseline deoxypyridinoline at the cutoff point noted had moderate sensitivity but high specificity for predicting these adverse skeletal events.

Aged↗
PubMed1999

Modulation by cytokines of glucocorticoid action.

Glucocorticoids (GC) are potent modulators of the inflammatory response. Their effects serve to down-regulate the inflammatory response and are mediated by genomic pathways that follow the interaction with specific receptors (glucocorticoid receptors, GR). Interleukin (IL)-1, IL-2, and IL-6 are able to increase GC secretion by enhancing synthesis and release of CRH and ACTH. Cytokine effects upon steroidogenesis also occur at the adrenal level. The role of cytokines as modulators of GR has received scarce attention. IL-1 has been shown to up-regulate GR mRNA expression in hypothalamic CRH secreting cells. On the other hand, macrophage migration inhibitory factor (MIF), a T-cell product inducible by inflammatory substances including other cytokines, counterregulates GC action within the immune system. Besides immunocytes and neurons, bone cells are a sensitive target for GC and cytokines. We have found that IL-2 and IL-6 up-regulate remarkably the number of GR binding sites and the expression of GR mRNA in peripheral blood mononuclear cells and in osteoblast-like Saos-2 cells. Available data suggest that inflammatory cytokines have both direct and indirect effects on GC action at the target level. Autocrine-induced transcription of GR in immunocytes and/or osteoblasts could be a mechanism that restrains excess cytokine production.

Animals↗