Pulmonary arterial hypertension: guidelines and unmet clinical needs.

The term pulmonary arterial hypertension (PAH) identifies a heterogeneous group of diseases characterized by a progressive increase in pulmonary arterial resistance (PVR), which causes a significant burden in terms of quality of life, right heart failure and premature death. The pathogenesis of PAH is not completely clear: the remodeling of the small pulmonary vessels is crucial, causing an increase in the resistance of the pulmonary circle. Its diagnosis is based on cardiac catheterization of the right heart. According to the present hemodynamic definition of pulmonary hypertension (PH) proposed by the Guidelines of the European Society of Cardiology/European Respiratory Society (ESC-ERS), the mean pulmonary arterial pressure (mPAP) values are ≥25 mmHg. In case of PAH, apart from an mPAP value ≥25 mmHg, patients must have a >3 Wood units increase in PVR and normal pressure values of the left heart. PH is a pathophysiological condition observed in more than 40 different diseases, while PAH is a primary disease of the pulmonary bloodstream potentially treatable with specific drugs. PAH is a severe complication of systemic sclerosis (SSc) affecting about 10% of the patients. Due to the devastating nature of SSc-PAH, there is a clear need to systematically adopt appropriate screening programs. In fact, despite awareness of the negative impact of SSc-PAH on quality of life and survival, as well as on the severity of lung function, at the moment standardized and shared guidelines and/or screening programs for the diagnosis and the subsequent early treatment of PAH in SSc are not available. The aim of the present paper is to highlight the lights and shadows of SSc-PAH, unraveling the unmet clinical needs on this topic with a proposal of clinical-diagnostic and therapeutic guidelines.

Congenital heart block and immune mediated sensorineural hearing loss: possible cross reactivity of immune response.

Immune-mediated sensorineural hearing loss may complicate systemic autoimmune diseases. We have previously reported the presence of antibodies directed against inner ear antigens in patients with Cogan syndrome, a disease characterized by sudden hearing loss and interstitial keratitis. Such autoantibodies cross-react with an epitope of SSA/Ro60 protein. Anti-Ro/SSA antibodies in pregnant women cross the placenta and reach the fetal tissues inducing an immune-mediated damage of the cardiac conduction system. We wanted to evaluate whether mothers with anti-Ro/SSA antibodies who gave birth to children with congenital heart block have antibodies directed against inner ear antigens and whether these antibodies are connected with the presence of immune-mediated sensorineural hearing loss. We did not find anti-inner ear antibodies in the majority of the mothers. On the contrary a 13-year-old boy with congenital heart block and sensorineural hearing loss was positive for the presence of anti-inner ear antigens antibodies. Moreover his serum was positive for the presence of anti-Ro60 peptide antibodies but did not recognize the entire protein Ro60 (TROVE2), a behaviour similar to that of sera from patients with Cogan syndrome. In conclusion the data obtained so far show that anti-inner ear antibodies do not recognize the entire protein TROVE2 and do not support the hypothesis that such antibodies may be involved in the pathogenesis of congenital heart block.

Secondary hypogammaglobulinemia in Waldmann's disease treated with subcutaneous immunoglobulins.

Primary intestinal lymphangiectasia (PIL) is rare disorder characterized by congenital malformation or obstruction of intestinal lymphatic drainage; it is responsible for protein losing enteropathy leading to lymphopenia, hypoalbuminemia and hypogammaglobulinemia. A low-fat diet associated with medium-chain triglyceride supplementation is the cornerstone of PIL management. The administration of intravenous immunoglobulins does not always lead to satisfactory plasma levels and therefore the replacement therapy with immunoglobulins is controversial. We describe here the case of a patient with PIL and severe hypogammaglobulinemia treated with immunoglobulins. The striking aspect of this case is the clinical and serological benefit obtained with the subcutaneous compared to the intravenous immunoglobulins administration.

Infections and autoimmunity: role of human cytomegalovirus in autoimmune endothelial cell damage.

Molecular mimicry between infectious agents and normal human host cell proteins represents one of the possible mechanisms responsible for autoimmunity. Among infectious agents, human cytomegalovirus (HCMV) is an ideal candidate for involvement in autoimmune disorders because of its lifelong persistence through periods of reactivation and latency and because of the extensive manipulation of innate and adaptive immunity. HCMV has been implicated in the pathogenesis of vascular damage in systemic sclerosis (SSc) and atherosclerosis. Based on our data, which demonstrate a cause-and-effect relationship between HCMV and endothelial cell aggression in SSc and atherosclerosis, we propose that immune responses to particular HCMV proteins may result in autoaggression through a mechanism of molecular mimicry of normally expressed endothelial cell surface molecules.

Gene expression profiling in dermatitis herpetiformis skin lesions.

Dermatitis herpetiformis (DH) is an autoimmune blistering skin disease associated with gluten-sensitive enteropathy (CD). In order to investigate the pathogenesis of skin lesions at molecular level, we analysed the gene expression profiles in skin biopsies from 6 CD patients with DH and 6 healthy controls using Affymetrix HG-U133A 2.0 arrays. 486 genes were differentially expressed in DH skin compared to normal skin: 225 were upregulated and 261 were downregulated. Consistently with the autoimmune origin of DH, functional classification of the differentially expressed genes (DEGs) indicates a B- and T-cell immune response (LAG3, TRAF5, DPP4, and NT5E). In addition, gene modulation provides evidence for a local inflammatory response (IL8, PTGFR, FSTL1, IFI16, BDKRD2, and NAMPT) with concomitant leukocyte recruitment (CCL5, ENPP2), endothelial cell activation, and neutrophil extravasation (SELL, SELE). DEGs also indicate overproduction of matrix proteases (MMP9, ADAM9, and ADAM19) and proteolytic enzymes (CTSG, ELA2, CPA3, TPSB2, and CMA1) that may contribute to epidermal splitting and blister formation. Finally, we observed modulation of genes involved in cell growth inhibition (CGREF1, PA2G4, and PPP2R1B), increased apoptosis (FAS, TNFSF10, and BASP1), and reduced adhesion at the dermal epidermal junction (PLEC1, ITGB4, and LAMA5). In conclusion, our results identify genes that are involved in the pathogenesis of DH skin lesions.

Depression and anxiety in perinatal period: prevalence and risk factors in an Italian sample.

Accumulating evidence suggests that pregnancy does not protect women from mental illness. The aim of this study was to assess the prevalence, sociodemographic correlates, and the risks factors for perinatal depression and anxiety. Five hundred ninety women between 28th and the 32nd gestational weeks were recruited and submitted to a sociodemographic, obstetric, and psychological interview. The Edinburgh Postnatal Depression Scale (EPDS) and the state-trait anxiety inventory (STAI-Y) were also administered in antenatal period and 3 months postnatally. The Structured Clinical Interview for DSM-IV (SCID-I) was used to diagnose mood and anxiety disorders. Three months after delivery, EPDS was administered by telephone interview. Women with an EPDS score ≥10 were 129 in antenatal period (21.9%) and 78 in postnatal period (13.2%). During pregnancy 121 women (20.5%) were positive for STAI-Y state and 149 women (25.3%) for STAI-Y trait. The most important risk factors for antenatal depression are: foreign nationality, conflictual relationship with family and partner, and lifetime psychiatric disorders. The principal risk factors for postnatal depression are: psychiatric disorders during pregnancy and artificial reproductive techniques. Psychiatric disorders, during and preceding pregnancy, are the strongest risk factors for antenatal state and trait anxiety. Antenatal depressive and anxiety symptoms appear to be as common as postnatal symptoms. These results provide clinical direction suggesting that early identification and treatment of perinatal affective disorders is particularly relevant to avoid more serious consequences for mothers and child.

New nitric oxide donors based on ruthenium complexes.

Nitric oxide (NO) donors produce NO-related activity when applied to biological systems. Among its diverse functions, NO has been implicated in vascular smooth muscle relaxation. Despite the great importance of NO in biological systems, its pharmacological and physiological studies have been limited due to its high reactivity and short half-life. In this review we will focus on our recent investigations of nitrosyl ruthenium complexes as NO-delivery agents and their effects on vascular smooth muscle cell relaxation. The high affinity of ruthenium for NO is a marked feature of its chemistry. The main signaling pathway responsible for the vascular relaxation induced by NO involves the activation of soluble guanylyl-cyclase, with subsequent accumulation of cGMP and activation of cGMP-dependent protein kinase. This in turn can activate several proteins such as K+ channels as well as induce vasodilatation by a decrease in cytosolic Ca2+. Oxidative stress and associated oxidative damage are mediators of vascular damage in several cardiovascular diseases, including hypertension. The increased production of the superoxide anion (O2-) by the vascular wall has been observed in different animal models of hypertension. Vascular relaxation to the endogenous NO-related response or to NO released from NO deliverers is impaired in vessels from renal hypertensive (2K-1C) rats. A growing amount of evidence supports the possibility that increased NO inactivation by excess O2- may account for the decreased NO bioavailability and vascular dysfunction in hypertension.

New nitric oxide donors based on ruthenium complexes

Nitric oxide (NO) donors produce NO-related activity when applied to biological systems. Among its diverse functions, NO has been implicated in vascular smooth muscle relaxation. Despite the great importance of NO in biological systems, its pharmacological and physiological studies have been limited due to its high reactivity and short half-life. In this review we will focus on our recent investigations of nitrosyl ruthenium complexes as NO-delivery agents and their effects on vascular smooth muscle cell relaxation. The high affinity of ruthenium for NO is a marked feature of its chemistry. The main signaling pathway responsible for the vascular relaxation induced by NO involves the activation of soluble guanylyl-cyclase, with subsequent accumulation of cGMP and activation of cGMP-dependent protein kinase. This in turn can activate several proteins such as K+ channels as well as induce vasodilatation by a decrease in cytosolic Ca2+. Oxidative stress and associated oxidative damage are mediators of vascular damage in several cardiovascular diseases, including hypertension. The increased production of the superoxide anion (O2-) by the vascular wall has been observed in different animal models of hypertension. Vascular relaxation to the endogenous NO-related response or to NO released from NO deliverers is impaired in vessels from renal hypertensive (2K-1C) rats. A growing amount of evidence supports the possibility that increased NO inactivation by excess O2- may account for the decreased NO bioavailability and vascular dysfunction in hypertension.

Antiflagellin antibodies recognize the autoantigens Toll-Like Receptor 5 and Pals 1-associated tight junction protein and induce monocytes activation and increased intestinal permeability in Crohn's disease.

BACKGROUND AND OBJECTIVES: Bacterial flagellin is considered an important antigen in Crohn's disease (CD) as it activates innate immunity through Toll-Like Receptor 5 (TLR5) engagement and induces an elevated adaptive immune response. Little is known about the presence of an autoimmune process in CD. We aimed to identify pathogenically relevant autoantigen targets in CD. METHODS: We screened a random peptide library with pooled sera of patients with active CD. Transepithelial flux of [3H] mannitol in T84 human intestinal epithelial cell line was used to study the epithelial barrier function. Monocyte activation was evaluated by surface expression of activation markers and by production of pro-inflammatory cytokines. Gene modulation of T84 cells exposed to antipeptide antibodies was analysed by gene array. RESULTS: We identified a peptide that shares homology with Salmonella typhimurium flagellin and with self-antigens such as TLR5 and cell junction protein, Pals 1-associated tight junction protein. The affinity-purified antipeptide antibodies recognized the self-antigens and induced increased intestinal epithelial cell permeability. Moreover, the antibodies induced monocyte activation upon binding TLR5. Finally, in cultured intestinal cells (T84) the purified antibodies induced the modulation of clusters of proinflammatory genes similar to the one induced by the engagement of TLR5 by its natural ligand flagellin. CONCLUSIONS: Antibodies directed against an immunodominant peptide of flagellin recognize self-antigens and are functionally active suggesting the presence of an autoimmune process that can both facilitate loss of tolerance to intestinal microflora by increasing cell permeability and amplify the innate immunity involvement through a novel mechanism of TLR5 activation.

Vitamin C improves the effect of a new nitric oxide donor on the vascular smooth muscle from renal hypertensive rats.

Impaired relaxation induced by the new nitric oxide (NO) donor [Ru(NH.NHq)(terpy)NO(+)](3+) (TERPY) has been observed in the aortic rings from renal hypertensive rats (2K-1C). An increased production of reactive oxygen species (ROS) in the aortas from 2K-1C rats are capable of reducing NO bioavailability. Therefore, this study aimed at investigating the effects of an antioxidant (vitamin C) on the relaxant effect of NO released from TERPY on the 2K-1C rat aorta. As for vascular reactivity, the potency of TERPY is greater in the control rats (2K) than in 2K-1C whereas the maximum relaxation (ME) is not significantly different between the 2K and 2K-1C rat aortas. The relaxation of TERPY is potentiated only in the 2K-1C aortic ring treated with vitamin C. TERPY has a lower effect in decreasing cytosolic Ca(2+) concentration ([Ca(2+)]c) in vascular smooth muscle cells (VSMCs) from 2K-1C rats. This effect is also potentiated in 2K-1C aortic cells treated with vitamin C, but it is not altered in 2K cells. The basal cytosolic NO concentration ([NO]c) is lower in 2K-1C than in 2K cells, and the bioavailability of the NO released from TERPY is larger in 2K than in 2K-1C VSMCs. The superoxide radical concentration ([O(2)(*-)]) is higher in the 2K-1C aorta, and vitamin C reduces the [O(2)(*-)] in the 2K-1C aorta. Taken together, these results show that in the aortas of renal hypertensive 2K-1C rats, released NO from the new NO donor is not available to produce a similar effect in 2K aorta due to increased [O(2)(*-)].

Caveolae dysfunction contributes to impaired relaxation induced by nitric oxide donor in aorta from renal hypertensive rats.

Relaxation induced by nitric oxide (NO) donors is impaired in renal hypertensive two kidney-one clip (2K-1C) rat aortas. It has been proposed that caveolae are important in signal transduction and Ca2+ homeostasis. Therefore, in the present study we investigate the integrity of caveolae in vascular smooth muscle cells (VSMCs), as well as their influence on the effects produced by NO released from both the new NO donor [Ru(NH.NHq) (terpy)NO+]3+ (TERPY) and sodium nitroprusside (SNP) on 2K-1C rat aorta. The potency of both TERPY and SNP was lower in the 2K-1C aorta that in the normotensive aorta [two kidney (2K)], whereas the maximal relaxant effect (ME) was similar in both 2K-1C and 2K aortas. In the 2K aorta, methyl-beta-cyclodextrin (CD) reduced both the potency of TERPY and SNP, and their ME compared with the control, but it had no effect on the potency and ME of these NO donors in 2K-1C aortas. The decrease in cytosolic Ca2+ concentration ([Ca2+]c) induced by TERPY was larger in 2K than in 2K-1C cells, and this effect was inhibited by CD in 2K cells only. Aortic VSMCs from 2K rats presented a larger number of caveolae than those from 2K-1C rats. Treatment with CD reduced the number of caveolae in both 2K and 2K-1C aortic VSMCs. Our results support the idea that caveolae play a critical role in the relaxant effect and in the decrease in [Ca2+]c induced by NO, and they could be responsible for impaired aorta relaxation by NO in renal hypertensive rats.

Evaluation of nanoparticles loaded with benzopsoralen in rat peritoneal exudate cells.

Psoralens are widely used for the treatment of hyperproliferative skin disease. In this work, we prepared nanoparticles (NP) containing a benzopsoralen (3-ethoxy carbonyl-2H-benzofuro[3,2-f]-1-benzopiran-2-one) by the solvent evaporation technique. We evaluated important NP parameters such as particle size, drug encapsulation efficiency, effect of the encapsulation process over the drug's photochemistry, zeta potential, external morphology, and in vitro release behavior. We also investigated the nanoparticle as a drug delivery system (DDS), as well as its target delivery to the action site, which is a very important parameter to increase the therapeutic use of psoralens and to reduce their side effects. The uptake of benzopsoralen-loaded PLGA nanoparticles by different kinds of cells found in rat peritoneal exudates was also studied. The photodamage promoted by irradiation with UV light revealed morphological characteristics of cell damage such as cytoplasmic vesiculation, mitochondrial damage, and swelling of both the granular endoplasmatic reticulum and nuclear membrane. This encapsulation method maintained the drug's properties and improved drug delivery to the target cell.

Juvenile psoriatic arthritis and acquired sensorineural hearing loss in a teenager: is there an association?

Autoimmune inner ear disease is a cause of sensorineural hearing loss, first described in 1979 by McCabe. The occurrence during rheumatic diseases is already documented in adults, but to our knowledge, this evidence is still lacking in children. A 13-yr-old girl affected by juvenile psoriatic arthritis, treated with etanercept, developed a bilateral and asymmetric sensorineural deafness. The patient significantly improved after steroid administration. Once ruled out the principal causes of sensorineural hearing loss, we also considered the hypothesis of an anti-TNF side effect. However, the clinical presentation, the efficacy on steroid treatment and the presence of inner ear auto-antibodies prompt us to consider autoimmune-SNHL as the most plausible diagnosis. The young age of our patient seems to suggest a genetic susceptibility to autoimmunity and supports the concept of associated autoimmune diseases.

Endothelin-1 serum levels correlate with MCP-1 but not with homocysteine plasma concentration in patients with systemic sclerosis.

OBJECTIVES: To determine whether homocysteine (Hcy) plasma levels are correlated with molecules indicative of endothelial cell and fibroblast activation, including endothelin-1 (ET-1) and monocyte chemoattractant protein-1 and -3 (MCP-1, MCP-3), in patients with systemic sclerosis (SSc). METHODS: Eighty-two patients were enrolled in this study; the control group included 75 age- and sex-matched subjects. Plasma Hcy was determined by high-performance liquid chromatography; folic acid, and vitamin B(12) plasma levels were determined by a chemiluminescence method. ET-1, MCP-1, and MCP-3 were determined by enzyme-linked immunosorbent assay (ELISA). Analysis of the 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene was performed by polymerase chain reaction (PCR) and digestion with the enzyme HinfI. RESULTS: Hcy levels were lower in patients whereas ET-1 was significantly higher in patients and correlated with MCP-1. Stratification of the patients on the basis of Hcy levels was not associated with any statistical difference in the concentration of ET-1, MCP-1, and MCP-3. Patients with diffuse disease presented the highest levels of ET-1 and MCP-1. The distribution of the MTHFR genotypes was not different in patients and controls. CONCLUSIONS: In SSc, Hcy plasma concentration does not influence ET-1, MCP-1, or MCP-3 levels. On the contrary, ET-1, a marker of vascular activation, correlates with MCP-1, a chemokine involved in the fibrotic process of SSc.

Cytosolic calcium concentration is reduced by photolysis of a nitrosyl ruthenium complex in vascular smooth muscle cells.

The effect of the NO donors cis-[RuCl(bpy)(2)(NO)](PF(6)) (RUNOCL) and sodium nitroprusside (SNP) on the cytosolic Ca(2+) concentration ([Ca(2+)](c)) was studied in cells isolated from the rat aorta smooth muscle of cells isolated from the rat aorta smooth muscle. SNP is a metal nitrosyl complex made up of iron, cyanide groups, and a nitro moiety; the RUNOCL complex is made up of ruthenium and bipyridine ligands, with chloride and nitrosyl groups in the ruthenium axial positions. Rat aorta smooth muscle cells were loaded with fluo-3 acetoxymethyl ester (Fluo-3 AM) and imaged by a confocal scanning laser microscope excited with the 488 nm line of the argon ion laser. Fluorescence emission was measured at 510 nm. One of the NO donors, RUNOCL (100 micromol/L) or SNP (100 micromol/L), was then added to the cell chamber and the fluorescent intensity percentage (%IF) was measured after 240 s. RUNOCL reduced the %IF to 60.0+/-10.0% of the initial value. After treatment with the soluble guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ) (10 micromol/L), the measurement of %IF was 81.0+/-5.0% (n=4). In the presence of tetraethylammonium (TEA) (1 mmol/L) the %IF was 79.0+/-6.4% (n=4). A combination of ODQ and TEA increased the %IF to 97.0+/-3.5% (n=4). As for SNP, it reduced the %IF to 81.4+/-4.7% (n=4), but this effect was inhibited by ODQ (%IF 94.0+/-3.6%; n=4) and TEA (%IF 88.0+/-2.1%; n=4). The combination of ODQ and TEA increased (%IF 92.0+/-2.8%; n=4). Taken together, these results indicate that both the new NO donor RUNOCL and SNP reduce [Ca(2+)](c). Our data also give evidence that soluble guanylyl cyclase and K(+) channels sensitive to TEA are involved in the mechanisms responsible for the reduction in [Ca(2+)](c) of the rat aorta smooth muscle cells.

Schnitzler's syndrome treated successfully with intravenous pulse cyclophosphamide.

Schnitzler's syndrome is a rare clinical condition characterized by chronic urticaria, intermittent fever, bone pain, arthralgia or arthritis, and monoclonal immunoglobulin M (IgM) gammopathy. Here we describe the case of a 48-year-old Italian female with a long history of arthralgia, leucocytosis, spiking fever, and chronic urticaria with severe pruritus. The IgM-kappa monoclonal component in the serum and bone densification on conventional X-ray with hyperfixation on bone technetium scanning at the distal part of the femurs and at the proximal part of the tibias were detected 4 years after the onset of the symptoms. After many ineffective treatments, the use of pulse cyclophosphamide (CPX) resulted in complete remission of the disease that is still lasting after a 2-year follow-up.

Efficacy of intravenous immunoglobulin in chronic idiopathic pericarditis: report of four cases.

Human intravenous immunoglobulins (hIVIgs) are used in two broad categories of diseases: immunodeficiency and autoimmunity. Among the immune-mediated diseases hIVIgs are of benefit in idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, and dermatomyositis. Chronic idiopathic pericarditis (CIP) is a chronic disease of unknown origin characterized by recurrent episodes of pericardial inflammation. The cause of the recurrence is unknown, although in some cases it may be traced to a viral infection and to the presence of antimyocardial antibodies. Since a viral infection can induce an autoimmune process through a mechanism of molecular mimicry, and since the optimal therapy for prevention of the recurrences has not been established, we reasoned that treatment with hIVIgs could be beneficial in our patients unresponsive to previous immunosuppressive therapies. We describe four patients affected by CIP treated with monthly high-dose hIVIgs (0.4 g/kg daily for 5 consecutive days) for five times followed by administration every 2 months. Three of the four patients could permanently discontinue steroid therapy and are still in remission after years of follow-up. Our experience suggests that hIVIgs therapy may be a useful and safe treatment for CIP in steroid-dependent patients.

In chronic idiopathic urticaria autoantibodies against Fc epsilonRII/CD23 induce histamine release via eosinophil activation.

BACKGROUND: Chronic idiopathic urticaria is a common skin disorder characterized by recurrent, transitory, itchy weals for more than 6 weeks. An autoimmune origin has been suggested based on the findings of auto-antibodies (Abs) directed against either the alpha subunit of the high-affinity IgE receptor or the IgE molecule in nearly half of the patients. OBJECTIVE: To identify other autoantigen targets in patients with chronic idiopathic urticaria. METHODS: We used pooled IgG derived from 133 patients with chronic idiopathic urticaria to screen a random peptide library to identify disease-relevant autoantigen peptides. Among the identified peptides, one was recognized by the vast majority of patients' sera. Abs against this peptide were affinity purified from the patients' sera and assayed for their ability to induce histamine release from basophils. RESULTS: We identified a peptide that showed similarity with the low-affinity IgE receptor (Fc epsilonRII/CD23) expressed on lymphomonocytes and eosinophils. Anti-peptide IgG Abs purified from the patients' sera bound cell surface CD23 and were able to induce histamine release from basophils. This effect appeared to be mediated by the release of major basic protein from eosinophils upon engagement of CD23. The same effects were obtained with the sera from mice immunized with the CD23 peptide. CONCLUSION: Our results indicate that patients with chronic idiopathic urticaria have Abs against CD23 and that eosinophils, which infiltrate the skin of these patients, play a crucial role in maintaining the disease through the release of major basic protein upon engagement of the low-affinity IgE receptor by such auto-Abs.

[Positron emission tomography with fluorodeoxyglucose in gastro-entero-pancreatic tumors: diagnostic role and prognostic implications]. / La tomografia ad emissione di positroni con fluorodesossiglucosio nei tumori neuroendocrini gastro-entero-pancreatici: ruolo diagnostico e implicazioni prognostiche.

From November 1994 to November 2004, seventy-seven patients with neuroendocrine gastro-entero-pancreatic tumor (71% pancreatic) were investigated with 18-fluorine-deoxi-glucose positron emission tomography (FDG-PET). PET results were compared with CT-scan, MRI and octreoscan scintigraphy and clinico-pathologic features of patients and survival. Overall PET sensitivity was 57%; 78% of malignant tumors, 67% of borderline and 17% of benign tumors were detected by FDG-PET. No duodenal tumor was detected by PET scan. Only 16% of primary less than 2 cm in size was localized. In 16% of cases PET scan provided new information able to change therapeutic management. In PET positive patients the addictive information obtained by PET scan when compared with octreoscan, MRI and CT scan were respectively 50% more, 26% more and 30% more. In malignant neuroendocrine tumors PET positivity was related to short survival. No patient with malignant tumor died for disease progression in the follow-up when PET was negative, while 13/35 PET positive patients died (p <0.003). FDG-PET proved to be a second line technique in neuroendocrine digestive tumors. PET results improve clinical staging of disease and is related to survival in malignant cases; in 16% of cases may change the therapeutic option.