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Abstract: Objectives:We have previously demonstrated that vitamin B12 (cobalamin)-deficient central neuropathy in the rat is associated with local overexpression of neurotoxic tumour necrosis factor (TNF)-α combined with locally decreased synthesis of neurotrophic epidermal growth factor (EGF). The aims of this study were to investigate whether a similar imbalance also occurs in the serum of adult patients with clinically confirmed cobalamin deficiency and whether it can be corrected by vitamin B12 replacement therapy. Patients and methods: We studied 34 adult patients with severe cobalamin deficiency, 12 patients with pure iron deficiency anaemia and 34 control subjects. Haematological markers of cobalamin deficiency and serum TNF-α and EGF levels were measured using commercial kits. Thirteen cobalamin-deficient patients were re-evaluated after 3 and 6 months of parenteral vitamin B12 treatment. Results: TNF-α was significantly higher (p < 0.01) and EGF significantly lower (p < 0.01) in the patients with cobalamin deficiency, but both were unchanged in patients with pure iron deficiency anaemia. In cobalamin-deficient patients the serum TNF-α levels correlated significantly with plasma total homocysteine levels (r = 0.425; p < 0.02). In the treated patients TNF-α and EGF levels normalised concomitantly with clinical and haematological disease remission. Conclusions: In humans, as in rats, cobalamin concentration appears to be correlated with the synthesis and release of TNF-α and EGF in a reciprocal manner, because cobalamin deficiency is accompanied by overproduction of TNF-α and underproduction of EGF. [ABSTRACT FROM AUTHOR]

Background: The 13C-octanoic breath test (13C-OBT), a recently developed technique to evaluate gastric emptying of solids, has been validated in comparison to scintigraphy with low caloric meals (250 kcal). However, there is consensus that for clinical studies total caloric load should be in excess of 300 kcal, but studies comparing 13C-OBT results after low and medium caloric meals are lacking. Methods: Ten healthy subjects were given a 250-kcal and a 550-kcal meal in randomized order. Gastric emptying was assessed simultaneously by ultrasonography and 13C-OBT. Breath samples were taken according to both classic (21 samples over 5 h) and simplified (11 samples) schedules. Results: Increasing the meal energy content resulted in significantly longer half emptying time (T½) estimates by both ultrasonography (P < 0.01, Wilcoxon test) and 13C-OBT (P < 0.05). T½ estimates by the two methods significantly correlated for both the 250 (r s = 0.733, P = 0.018) and the 550 (r s = 0.637, P = 0.035) kcal meal. However, differences between T½ estimates by 13C-OBT and ultrasonography were greater after the 550- than the 250-kcal meal (median 172.5 versus 76.5 min, P < 0.05). Interindividual variability was also 2-fold greater for indexes estimated by 13C-OBT with the 550-kcal meal compared with the 250-kcal meal. For both meals 13C-OBT yielded similar results with the classic and simplified schedules. Conclusions: In healthy subjects caloric intake is a major determinant of gastric emptying rate. However, after a medium caloric meal 13C-OBT shows some inaccuracy, which raises questions about its routine clinical application. Nevertheless, when using 13C-OBT one must take into account that the simplified schedule is just as effective as the classic one, and is far lower in cost. [ABSTRACT FROM AUTHOR]

Background: As abnormalities of circulating gut regulatory peptides may have pathogenetic relevance in chronic idiopathic slow-transit constipation, we measured fasting and postprandial levels of plasma pancreatic polypeptide, motilin, cholecystokinin, neurotensin, and somatostatin in women with the disease. Results were compared with those of women with normal bowel habits. Methods: Eight women with slow-transit constipation and 10 healthy women were studied. Blood samples were taken at regular intervals in fasting conditions and for 3 h after a standard solid-liquid meal (550 kcal). Gut peptide plasma levels were measured with a radioimmunoassay. Results: Fasting gut peptide levels and postprandial pancreatic polypeptide responses were normal in constipated patients, in whom, however, motilin levels did not increase after the meal, and postprandial concentration-time curves of cholecystokinin, neurotensin, and somatostatin were delayed. Mean ± standard error of the mean peak times in patients and in controls were, respectively, 99 ± 14.7 and 46 ± 4.1 min (P < 0.01, Mann-Whitney test) for cholecystokinin, 135 ± 9.8 and 60 ± 3.9 min (P < 0.01) for neurotensin, and 111 ± 17.7 and 51 ± 6.0 min (P < 0.05) for somatostatin. Conclusions: Patients with slow-transit constipation have abnormal postprandial patterns of motilin, cholecystokinin, neurotensin, and somatostatin. [ABSTRACT FROM AUTHOR]

The article studies the circulating ghrelin levels in inflammatory bowel disease (IBD) patients. The endocrine and non-endocrine effects of the gut-brain peptide include control of food intake and energy homeostasis. Fasting serum total ghrelin levels, tumor necrosis factor α and C-reactive protein are evaluated in IBD patients and health controls. To measure serum ghrelin, radioimmunnoassay is used.

Background: Upper gastrointestinal motor abnormalities could account for some of the dyspeptic symptoms of celiac patients. However, the data on gastric emptying time are conflicting, and the pathophysiology of motor disturbances is still unclear. Neurotensin modulates upper gastrointestinal motor activity, and its postprandial increase is a reliable index of nutrient delivery to the ileum. We therefore assessed both plasma neurotensin levels and gastric emptying in untreated celiacs. Methods: The gastric antral area of nine untreated celiac patients and nine controls was measured with ultrasound at base line and every 30 min after a fatty meal (227 kcal, 45% fat); the base-line and postprandial neurotensin plasma levels were determined by means of radioimmunoassay. The data are mean values ± standard deviation and were analyzed by using non-parametric tests. Results: The overall and half gastric emptying time were significantly longer in the patients (203 ± 32 versus 133 ± 15 min, P = 0.0117, and 137 ± 32 versus 78 ± 11 min, P = 0.0001). The pattern of the changes in antral area was similar in both groups during the observation period as a whole but differed significantly in the first 120 min (P = 0.0343). Base-line neurotensin levels were significantly higher in the patients (41.6 ± 23.9 versus 18.2 ± 5.5 pg/ml, P = 0.0214) and their net postprandial increase was lower than in controls (15.0 ± 15.9 versus 29.8 ± 13.0 pg/ml, P = 0.046). In both groups the base-line neurotensin levels were related to the half gastric emptying time (P = 0.023). Conclusions: In untreated celiac patients gastric emptying time is longer than in controls and is concomitant with an increase in base-line plasma neurotensin levels. [ABSTRACT FROM AUTHOR]

Background: Liver metastases are a strong prognostic indicator in patients with gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs). Therapeutic options for metastatic NETs are expanding and not mutually exclusive.Aims: This paper reviews the literature relating to multidisciplinary approach towards GEP-NET metastases, to highlight advances in knowledge regarding these tumors, and to understand the interdisciplinary management of individual patients.Methods: A PubMed search was performed for English-language publications from 1995 through 2012. Reference lists from studies selected were manually searched to identify further relevant reports. Manuscripts comparing different therapeutic options and advances for GEP-NET-related liver metastases were selected.Results: There is considerable controversy regarding the optimal management of GEP-NET metastases. Although radical surgery still remains the gold standard, a variety of other therapeutic options are available for metastatic GEP-NETs, including loco-regional chemotherapy/radiotherapy, radioembolization, systemic peptide receptor radionuclide therapy, biotherapy, and chemotherapy. In selected patients, liver transplantation should also be considered. Systemic somatostatin analogues and/or interferon show anti-proliferative effects, representing an appropriate first-line treatment for most patients. In advanced metastatic NETs, recent options include targeted therapies (i.e., everolimus and sunitinib).Conclusions: It is evident that multidisciplinary care and multimodality treatments remain the cornerstone of management of NET patients. Since NETs often show a more indolent behavior compared to other malignancies, physicians should aim to preserve a satisfactory quality of life for the patient by personalizing the therapeutic approach according to the tumor's features and prognostic factors. [ABSTRACT FROM AUTHOR]

Introduction: Both multiple endocrine neoplasia type 1 (MEN1)-related-gastrinomas and Gastrointestinal Stromal Tumors (GISTs) are rare neoplasms, and their association has been rarely reported. Aim(s): We present a case of a man with an esophageal GIST and previously an MEN1-related pancreatic gastrinoma. Materials and methods: The present report refers to a 44-year-old man who underwent surgical removal of a cephalopancreatic gastrinoma, peripancreatic lymph nodes and liver metastasis in April of 2004. The patient was then given long-term somatostatin analogs and diagnosed as having MEN-1 syndrome. The follow-up was uneventful until April 2009, when the patient reported a return of heartburn. The clinical assessment excluded a recurrence of gastrinoma, while upper gastrointestinal (GI) tract endoscopy findings were consistent with a narrowing of the distal third of the esophagus. Results: Endoscopic ultrasonography showed a hypoechoic 2 cm solid mass in the distal esophagus, which was sampled and revealed a tumor composed of elongated cells with a plump cytoplasm arranged in a storiform pattern suggestive of a mesenchymal lesion, consistent with GIST. Conclusion: The association of GISTs and MEN-1 could be purely casual because no evidence of genetic mechanisms responsible for their simultaneous occurrence has been reported. Nevertheless, further genetic studies are warranted to exclude a role of the MEN-1 gene in the pathogenesis of GISTs. [ABSTRACT FROM AUTHOR]

Introduction: Gastroenteropancreatic neuroendocrine tumors (GEP NET) are heterogeneous neoplasms with different malignancy. Plasma chromogranin A (CgA) may play an important role in predicting outcome. Aim(s): To evaluate the clinical utility of CgA in diagnosing and monitoring GEP NET patients. Materials and methods: One-hundred and eighty-one GEP NET patients were diagnosed and followed-up from 1995 to 2010:81 had pancreatic NET, 31 gastric, 18 duodenal, 37 ileal, three colonic and 11 rectal. 105 were NET G1, 64 NET G2 and 12 NEC G3, according to WHO 2010 classification; 81 were classified in stage I, 14 in stage II, 17 in stage III and 69 in stage IV. CgA values were collected at diagnosis and during follow-up. Surgical interventions, medical treatment, comorbidities, causes of death, and survival were evaluated. Results: At diagnosis, plasma CgA values showed an overall sensitivity of 82% and correlated with age, WHO 2010 classification, TNM staging, Ki-67 index(p<0.0001). Factors significantly associated with mortality were advanced TNM staging, WHO 2010 classification, Ki-67 index, treatment received and basal CgA levels (p<0.0001). Patients with an early CgA decrease after treatment had a higher median survival (60 v. 24 months, p<0.0001), compared with those without. Among patients who underwent radical surgery, 15 have relapsed and in seven, CgA values increased significantly with an advance of 12 months, compared to objective recurrence. Conclusion; In GEP-NET, plasma CgA is not only a reliable marker, but it also plays an important prognostic role. [ABSTRACT FROM AUTHOR]

Painful sensory neuropathies consist of a wide range of neuropathies that can involve large as well as small nerve fibres. Even if most cases remain of unknown cause, some of them may be associated with an underlying disorder such as diabetes, HIV, infections, amyloidosis, and Sjogren's syndrome. Since in some cases an autoimmune mechanism has been postulated, we investigated a panel of circulating autoantibodies including anti-gliadin (AGA), anti-endomysium (EmA), anti-transglutaminase (tTGA) and anti-nuclear (ANA) antibodies in the sera of patients with unexplained painful sensory neuropathies in order to identify other potentially treatable disorders. We tested the sera of 10 patients (4M; 6F) previously investigated for other causes of neuropathies, including anti-nerve, onconeural, anti-extractable nuclear, anti-neutrophil cytoplasmic, anti-thyroglobulin (TgA) and anti-peroxidase (TPOA) antibodies. We found the presence of AGA positivity in 4 patients (40%), ANA in 7 (70%) and AGA + ANA in 4 (40%), two of whom were negative for celiac disease by gastrointestinal biopsy. None of the patients had EmA positivity. Three (30%) had TgA and TPOA and none had anti-nerve or onconeural antibodies. Whether the presence of circulating autoantibodies in patients with unexplained painful neuropathy reflects an autoimmune involvement which may be amenable to immune therapy and not only to symptomatic treatment remains to be established. [ABSTRACT FROM AUTHOR]