Preoperative administration of Omega-3 fatty acids on postoperative pain and acute-phase reactants in patients undergoing Roux-en-Y gastric bypass: A randomized clinical trial.

BACKGROUND: The term "Immunonutrition" (IMN) describes the enteral administration of certain substrates with a theoretical immunomodulating function. From all the elements conforming these IMN formulas, Omega-3 fatty acids (O3FA) are hypothesized to be the most important component for immunomodulation, with increased anti-inflammatory and antioxidant effect. PATIENTS AND METHODS: A prospective randomized clinical trial of all the patients undergoing laparoscopic Roux-en-Y gastric bypass was performed. Patients were randomly assigned into 2 groups: those patients receiving a preoperative balanced energy high-protein formula (Control Group) and those ones who received the same preoperative nutritional formula enriched with O3FA (Experimental Group). In both groups, there was a restriction to 900 Kcal/day. Nutritional intervention started 10 days before surgery and was maintained up to 8 h before the surgical act. Preoperative weight loss, postoperative pain, complications and acute phase reactants were investigated. RESULTS: 40 patients were included in the study, 20 in each group. Preoperative excess weight loss (EWL) with the prescribed treatment was 10.6 ± 7.7% in Control Group and 14.1 ± 5.8% in the Experimental Group (p = 0.024). Mean postoperative pain was 25 ± 9.2 mm in Control group and 10,9 ± 4,4 mm in Experimental Group (p = 0.015). CRP determined 24 h after surgery was significantly lower in the Experimental Group than in the Control Group. There were not significant differences in complications, mortality or readmission rates between groups. CONCLUSIONS: The use of a nutritional supplement enriched with O3FA is associated with a greater preoperative weight loss, reduced postoperative pain and decreased postoperative levels of C reactive protein.

Analysis of IGF(CA)19 and IGFBP3-202A/C gene polymorphisms in patients with acromegaly: association with clinical presentation and response to treatments.

OBJECTIVE: IGF1 and IGFBP3 gene polymorphisms have been recently described. However, their potential role in the setting of acromegaly and its outcome is unknown. In this study, we analyze these polymorphisms in patients with acromegaly and investigate their association with clinical presentation and response to treatments. DESIGN: A retrospective observational study was conducted in patients with acromegaly to analyze IGF1 and IGFBP3 gene polymorphisms. METHODS: A total of 124 patients with acromegaly (57.3% women, mean age 44.9±13.1 years old) were followed up for a period of 11.4±8.0 years in eight tertiary referral hospitals in Spain. Clinical and analytical data were evaluated at baseline and after treatment. IGF1 and IGFBP3 gene polymorphisms were analyzed using PCR and specific primers. RESULTS: Baseline laboratory test results were GH 19.3 (8.0-39.6) ng/ml, nadir GH 11.8 (4.1-21.5) ng/ml, and index IGF1 2.65±1.25 upper limit of normal. Regarding the IGF1 gene polymorphism, we did not find any association between the number of cyto-adenosine (CA) repeats and patients' baseline characteristics. Nevertheless, a trend for higher nadir GH values was observed in patients with <19 CA repeats. Regarding the IGFBP3 polymorphism, the absence of an A allele at the -202 position was associated with a higher baseline IGF1 and a higher prevalence of cancer and polyps. There were no differences in response to therapies according to the specific genotypes. CONCLUSIONS: Polymorphisms in the IGF1 and IGFBP3 genes may not be invariably determinant of treatment outcome in acromegalic patients, but they may be associated with higher nadir GH levels or baseline IGF1, and determine a higher rate of colorectal polyps and cancer.

Analysis of expression and function of the inhibitory receptor ILT2 in lymphocytes from patients with autoimmune thyroid disease.

OBJECTIVE: Autoimmune thyroid disease (AITD) is characterized by different defects in immunoregulatory mechanisms. The immunoglobulin-like transcript receptor 2 (ILT2) or leukocyte Ig-like receptor 1 (LIRB1/CD85j) exerts an important immunoregulatory role. We hypothesized that the lymphocytes from AITD patients have a diminished expression and function of ILT2. The aim of this study was to investigate the expression and function of ILT2 in lymphocytes from patients with AITD. DESIGN AND METHODS: In this study, 18 patients with Hashimoto's thyroiditis (HT), 20 with Graves' disease, and 26 healthy controls were studied. ILT2 expression was analyzed by flow cytometry and immunohistochemistry in peripheral blood mononuclear cells (PBMC) and thyroid tissue. The regulatory function of ILT2 was assessed by an assay of inhibition of lymphocyte proliferation and by an analysis of cell cycle progression. The effect of ILT2 on cytokine synthesis was also evaluated. RESULTS: We found a significant increased expression of ILT2 by lymphocytes in AITD patients. ILT2 was also detected in the leukocyte infiltrate of thyroid tissue from HT patients. On the contrary, a significant diminished inhibitory activity of ILT2 on cell proliferation was observed in AITD patients. In addition, PBMC from AITD patients showed a diminished synthesis of interleukin 10 on ILT2 engagement. CONCLUSIONS: The abnormal expression and function of ILT2 detected in AITD suggests that this receptor may participate in the pathogenesis of this condition.

The association of the angiopoietin/Tie-2 system with the development of metastasis and leukocyte migration in neuroendocrine tumors.

The aim of this study was to explore the possible involvement of the angiopoietin (Ang)-1, -2/Tie-2 system in the development, growth, and metastases evolution of gastroenteropancreatic-neuroendocrine tumors (GEP-NETs). We prospectively examined the serum levels of Tie-2, Ang-1, and Ang-2 by ELISA in 42 patients with proven GEP-NETs and 27 controls. We also determined the expression of the Ang/Tie-2 system in freshly isolated peripheral blood monocytes and in tumor cells from malignant primary tumors and/or liver metastases samples from GEP-NET patients by flow cytometry and/or RT-PCR. Furthermore, the function of the Ang/Tie-2 system in monocytes from controls and patients was assessed by a chemotaxis assay. GEP-NET patients showed enhanced serum levels of soluble form of Tie-2 (sTie-2), Ang-1, and Ang-2 (P<0.05 in all cases), compared to controls. sTie-2 and Ang-2 levels were significantly higher in GEP-NETs with metastases compared to those with no metastases. In addition, a significant correlation was detected between Ang-2 levels and chromogranin A or sTie-2 concentrations or 5-hydroxy-indole acetic acid excretion (r=0.71, r=0.60, and r=0.81 respectively, P<0.01 in all cases). Furthermore, we observed an enhanced expression of Ang-1, Ang-2, and Tie-2 in freshly isolated tumor cells from GEP-NET both by immunohistochemistry and by RT-PCR. Interestingly, an enhanced expression and function of Tie-2 was detected in monocytes from GEP-NET patients. Our data suggest that the Ang/Tie-2 system is involved in the growth and development of metastases of GEP-NETs, and that favors the recruitment of Tie-2(+) monocytes to the tumor site, where they can promote inflammation and angiogenesis.

Pegvisomant-induced liver injury is related to the UGT1A1*28 polymorphism of Gilbert's syndrome.

CONTEXT: Pegvisomant (PEG) therapy has been associated with drug-induced liver dysfunction in acromegalic patients. The mechanism of its toxicity remains unknown. OBJECTIVE: The primary objective was to determine whether or not the UGT1A1*28 polymorphism associated with Gilbert's syndrome influences the development of liver dysfunction during PEG treatment. DESIGN AND SETTING: A cross-sectional study was conducted in four Spanish university hospitals. PATIENTS: Thirty-six acromegalic patients with active disease, resistant to somatostatin analogs, participated. RESULTS: The prevalence of the UGT1A1*28 homozygous and heterozygous genotypes in acromegalic patients was 14 and 44%, respectively. Ten patients (28%) developed liver function test (LFT) abnormalities. There was a tendency for more frequent liver function abnormalities in males (70% males vs. 30% females, P = 0.058). Carriers of the UGT1A1*28 polymorphism had a higher incidence of LFT abnormalities than the UGT1A1 wild type (43% carriers vs. 7% wild type, P = 0.024). This difference persisted when adjusted in an all-factors multiple regression analysis [coefficient of determination (R(2)) = 0.463; P = 0.008] for age, gender, alcohol consumption, and UGT1A1*28 polymorphism. A stepwise multivariate likelihood binary logistic regression analysis (R(2) = 0.40; P = 0.003) identified male gender (beta = 7.21; P = 0.033) and UGT1A1*28 polymorphism (beta = 14.1; P = 0.028) as the only significant predictors for the development of LFT abnormalities. CONCLUSIONS: The UGT1A1*28 genotype and male gender predict an increased incidence of LFT abnormalities during PEG therapy in acromegaly.