Vincenzo Pilone

miR-519d overexpression is associated with human obesity.

Obesity is a consequence of imbalance of food intake and energy expenditure that results in storage of energy as fat, primarily in adipose tissue. MicroRNAs are non‐coding RNAs that regulate gene expression in metabolic pathways and they are also involved in fat‐cell development. The aim of this study was to evaluate whether microRNA dysfunction contributes to obesity. We analyzed, by microarray, the expression profile of 1,458 microRNAs in subcutaneous adipose tissue (SAT) from nondiabetic severely obese (n = 20) and nonobese adults (n = 8). Among 42 differently expressed microRNAs, we confirmed by reverse‐transcription PCR (RT‐PCR) that miR‐519d was overexpressed whereas the protein levels of peroxisome proliferator‐activated receptor‐α (PPARA) (a predicted miR 519d target) were lower, at western analysis, in severely obese vs. nonobese subjects. We also show that miR‐519d specifically and dose‐dependently suppressed translation of the PPARA protein, and increased lipid accumulation during preadipocyte differentiation. Because PPARA plays a central role in fatty acid homeostasis, and in the transcriptional regulation of genes that are necessary for maintenance of the redox balance during the oxidative catabolism of fatty acids, we suggest that PPARA loss and miR‐519d overexpression could be associated with metabolic imbalance and subsequent adipocyte hypertrophy in SAT during obesity.

Heliosphere® bag in the treatment of severe obesity : Preliminary experience

Background: Various intragastric balloons have been used in obese patients for temporary weight loss. Recently, a new balloon, the Heliosphere® Bag, was proposed. In a preliminary study, we evaluated the safety and efficacy of this device. Methods: The Heliosphere® Bag was used in 10 patients, selected according to the guidelines for obesity surgery. The manufacturers instructions were followed in positioning the device. Heliosphere® Bag positioning was performed, after diagnostic endoscopy, under unconscious sedation. After placement, the balloon was slowly inflated with 840-960 cc of air, which gives the inflated final volume of 650-700 cc of air, as the air is compressed. On the first and second post-treatment day, intravenous saline (30-35 ml/kg/d) with omeprazole (20 mg/d), ondansetron (8 mg/d) and butylscopolamine bromide (20 mg t.i.d.) were given to all patients. All patients from day 3 after placement began liquid diet and were discharged home on day 4 on a 1000 kcal diet (carbohydrate 146 g, lipid 68 g, protein 1 g/kg ideal weight). After 6 months, the Heliosphere® Bag was removed. The patients were followed monthly, and complications and their treatment, post-placement symptoms, BMI and %EWL were recorded. Data were expressed as mean ± SD. Results: From Sept-Dec 2004, 10 patients (5M/5F) underwent Heliosphere® Bag placement, with age 35.2 ± 15.7 years (17-49), BMI 43.3 ± 8.1 kg/m2 (35-51.2), and weight 126.8 ± 23.7 kg (98.4-148). Heliosphere® Bag positioning was quite difficult in all patients due to low pliancy and large size of the bag, causing patient discomfort. System failure at time of Heliosphere® Bag positioning was observed in 5/10 patients (50%). At time of removal, the Heliosphere® Bag was not found in the stomach in one patient. In 3 other patients, the balloon was found partially deflated. At the time of balloon removal after 6 months, BMI was 37.4 ± 13.4 (28.9-42.1) and %EWL was 29.1 ± 20.1 (9.0-57.4). BMI loss was 5.2 ± 13.1 (1.9-11.2) and mean weight loss was 17.5 ± 16.2 kg (5-33). Conclusions: Although weight loss was satisfactory, this device cannot be considered an advance for the temporary treatment of morbid obesity. This balloon still has some instrumental and technical problems that need to be solved: high rate of system failure at positioning, high rate of spontaneous deflation, absence of a marker such as methylene blue, and large size with low pliability that cause significant patient discomfort.

Adiponectin oligomers as potential indicators of adipose tissue improvement in obese subjects.

OBJECTIVE Adiponectin is an adipocytokine that exerts beneficial effects on obesity and related disorders by two receptors (ADIPORs). Adiponectin is produced as a monomer that circulates in serum as different oligomers. The oligomerization state and the tissue expression of adiponectin and ADIPORs are linked to its biological activities. In this study, the levels of total adiponectin and its oligomers were evaluated in relation to obesity and surgical weight loss. The expression of adiponectin and ADIPORs was analyzed in visceral and subcutaneous adipose tissues of obese patients. DESIGN AND METHODS In 25 obese patients and 44 age- and sex-matched controls, the serum levels of adiponectin and its oligomers were measured and compared by ELISA, western blotting, and gel filtration. The expression of adiponectin and ADIPORs in both adipose tissues was evaluated by real-time quantitative PCR and western blotting. RESULTS The amount of each adiponectin oligomer, including the monomer, increases after weight loss. The reduced circulating levels of adiponectin and its oligomers are not associated with the adipose tissue depot-specific expression of adiponectin and ADIPORs. CONCLUSIONS Our results suggest that in patients, adiposity is associated with the serum concentrations of adiponectin and its oligomers but not with adipose tissue depot-specific expression of adiponectin and ADIPORs. In particular, the increase in adiponectin monomer levels could probably be related to the improvement of the whole-body energy metabolism then being involved in the improvement of adipose tissue function after weight loss. This work indicates the importance of assessing the whole adiponectin oligomeric profile as further potential indicators of adipose tissue functions in obesity.

Improvement in health-related quality of life in first year after laparoscopic adjustable gastric banding

BACKGROUND We analyzed the health-related quality of life (HRQOL) and its determinants in the first year after laparoscopic adjustable gastric banding (LAGB). The setting was 10 Italian public and private bariatric surgery centers. METHODS Data collected in an ongoing, prospective, 3-year multicenter Italian study on the changes in HRQOL after LAGB were used. HRQOL was investigated using the Medical Outcomes Study Short-Form 36 questionnaire. Hunger, satiety, and the self-perceived effects of LAGB were recorded. RESULTS A total of 334 patients were enrolled. The follow-up rate was 92.2%. The percentage of excess weight loss was 39.6% ± 25.8%, with very few side effects or complications. Hunger in the morning (0-10 scale) was 4.5 ± 2.7 before surgery and 3.8 ± 2.4 after 1 year (P <.001). Satiety after a meal (0-10 scale) was 7.1 ± 2.7 before surgery and 8.2 ± 1.9 at 1 year (P <.001). The self-perceived effect of LAGB on caloric intake (0-10 scale) was 8.4 ± 1.9 after 1 year. The scores for the 8 Medical Outcomes Study Short-Form 36 subscales were significantly improved after surgery. The physical component summary score was 52.6 ± 11.9 at baseline and 79.1 ± 15.6 after 1 year (P <.001). The corresponding mental component summary scores were 52.2 ± 12.3 and 76.5 ± 17.2 (P <.001). Greater physical component summary improvement was independently associated with a low initial physical component summary (P <.001), high satiety (P = .002), a high percentage of excess weight loss (P = .013), and a high self-perceived effect of the LAGB (P = .026). Greater mental component summary improvement was associated with a low initial mental component summary (P <.001), high satiety (P <.001), a low frequency of heartburn (P = .004), and a high percentage of excess weight loss (P = .012). CONCLUSIONS Significant improvements in HRQOL were observed in the first year after LAGB. A poor baseline HRQOL, a high efficacy of the banding in eating control, and better weight loss might influence HRQOL changes.

Clinical impact of Mediterranean-enriched-protein diet on liver size, visceral fat, fat mass, and fat-free mass in patients undergoing sleeve gastrectomy

BACKGROUND Weight loss before laparoscopic sleeve gastrectomy (LSG) is desirable because it can reduce visceral fat and liver size thereby facilitating the surgical procedure. Preoperative very-low-energy diets have been demonstrated to decrease weight, visceral fat, and liver size. However, no studies have been conducted using the Mediterranean-protein-enriched diet (MPED) or on the amount of preoperative weight loss attributed to the loss of fat-free mass (FFM). OBJECTIVES To evaluate the effect of the MPED on weight, visceral fat, liver size, fat mass (FM), and FFM in obese patients undergoing LSG. SETTING University Hospital, Italy. MATERIALS AND METHODS Obese male patients (n = 37) with a mean body mass index (BMI) of 45.2 kg/m(2) scheduled for LSG underwent an 8-week preoperative MPED. Their weight, visceral fat, body composition, liver size, and biochemical and metabolic patterns were measured before and after the diet. Patient compliance was assessed by the presence of ketonuria and weight loss. Qualitative methods (5-point Likert questionnaire) were used to measure diet acceptability and side effects. RESULTS We observed highly significant decreases in weight, liver size, visceral fat, and FM; however, there was no significant reduction in FFM. All tested patients showed a high frequency of acceptability and compliance in following the diet, and no secondary effects were observed. CONCLUSION Based on our findings, we were able to support the hypothesis that MPED might be associated with significant reductions in weight loss, FM, and liver size without a significant loss of FFM.

Acinic cell carcinoma of the breast: Review of the literature

INTRODUCTION The breast and salivary gland tissue share embryologic and thus pathological similarities. Acinic cell carcinoma (ACC) is a typical tumor in salivary glands, but rarely arises in breast too. We reviewed 38 cases of mammary ACC reported in literature and our case, the first ACC born within a fibroadenoma. MATERIALS AND METHODS Data were collected by a research for the key words acinic cell carcinoma breast on Pubmed in March 2014, including a case treated in our department. All reviewed cases were compared for clinical approach and histological pattern. RESULTS To date 23 articles presenting cases of ACC of the breast are reported in literature. We included in our review 38 cases previously described and one new case. The histological pattern was predominantly solid with a microglandular structure. All the tumor cells were cytologically characterized by monotonous round cells with a finely granular, weakly eosinophilic, or clearly vacuolated cytoplasm. The most of the cells were intensely stained with anti-lysozime, anti-amylase, anti-α1-chimotripsin, anti-EMA and anti-S100 protein antisera. Immunohistochemistry was also performed to point out: estrogen receptor (ER), progesterone receptor (PR), androgen receptors (AR), human epidermal growth factor receptor 2 overexpression (HER2/neu), E-cadherin (E-cad), cytokeratin-7 (CK7), gross cystic disease fluid protein 15 (GCDFP15), smooth muscle actin (SMA). CONCLUSION ACC of the breast is a rare tumor, showing similarities with the salivary gland counterpart, above all in terms of good prognosis, and differences from the ordinary invasive breast carcinoma. Further investigations are needed to elucidate the true histogenesis and the correct treatment.

LigaSure Haemorrhoidectomy versus Conventional Diathermy for IV-Degree Haemorrhoids: Is It the Treatment of Choice? A Randomized, Clinical Trial.

Introduction. Milligan-Morgan haemorrhoidectomy performed with LigaSure system (LS) seems to be mainly effective where a large tissue demolition is required. This randomized study is designed to compare LigaSure haemorrohidectomy with conventional diathermy (CD) for treatment of IV-degree haemorrhoids. Methods. 52 patients with IV-degree haemorrhoids were randomized to two groups (conventional diathermy versus LigaSure haemorrhoidectomy). They were evaluated on the basis of the following main outcomes: mean operative time, postoperative pain, day of discharge, early and late complications. The time of recovery of work was also assessed. All patients had a minimum follow-up of twelve months (range 12–24). All data were statistically evaluated. Results. 27 patients were treated by conventional diathermy, 25 by LigaSure. The mean operative time was significantly shorter in LS, such as postoperative pain, mainly lower on the third and fourth postoperative day: moreover pain disappeared earlier in LS than CD. The time off-work was shorter in LS, while there was no difference in hospital stay and overall complications rate. Conclusions. LigaSure is an effective instrument when a large tissue demolition is required. This study supports its use as treatment of choice for IV degree haemorrhoids, even if the procedure is more expansive than conventional operation.

Micronutrient Deficiencies in Patients Candidate for Bariatric Surgery: A Prospective, Preoperative Trial of Screening, Diagnosis, and Treatment

Bariatric surgery candidates often show preoperative micronutrient deficiency. Although it is documented that a comprehensive micronutrient assessment should be conducted preoperatively to correct the deficiencies before surgery, no previous studies have been effective in correcting deficiencies in sufficient time prior to surgery. Our aim was to identify micronutrient deficiencies preoperatively and correct them before surgery.

Changes in the MicroRNA Profile Observed in the Subcutaneous Adipose Tissue of Obese Patients after Laparoscopic Adjustable Gastric Banding

Background. Laparoscopic adjustable gastric banding (LAGB) results in significant lasting weight loss and improved metabolism in obese patients. To evaluate whether epigenetic factors could concur to these benefits, we investigated the subcutaneous adipose tissue (SAT) microRNA (miRNA) profile before (T0) and three years (T1) after LAGB in three morbidly obese women. Case Reports. SAT miRNA profiling, evaluated by TaqMan Array, showed four downexpressed (miR-519d, miR-299-5p, miR-212, and miR-671-3p) and two upexpressed (miR-370 and miR-487a) miRNAs at T1 versus T0. Bioinformatics predicted that these miRNAs regulate genes belonging to pathways associated with the cytoskeleton, inflammation, and metabolism. Western blot analysis showed that PPAR-alpha, which is the target gene of miR-519d, increased after LAGB, thereby suggesting an improvement in SAT lipid metabolism. Accordingly, the number and diameter of adipocytes were significantly higher and lower, respectively, at T1 versus T0. Bioinformatics predicted that the decreased levels of miR-212, miR-299-5p, and miR-671-3p at T1 concur in reducing SAT inflammation. Conclusion. We show that the miRNA profile changes after LAGB. This finding, although obtained in only three cases, suggests that this epigenetic mechanism, by regulating the expression of genes involved in inflammation and lipid metabolism, could concur to improve SAT functionality in postoperative obese patients.

Three years durability of the improvements in health-related quality of life observed after gastric banding

BACKGROUND Improvements in health-related quality of life (HR-QoL) occur after bariatric surgery. However, sustainability of these changes over time remains debated. METHODS Data collected in a prospective 3-year multicenter Italian study on changes of HR-QoL after laparoscopic adjustable gastric banding were used. HR-QoL has investigated with the SF-36 questionnaire. Hunger, satiety, and the self-perceived effects of LAGB were recorded. RESULTS A total of 230 patients (53 male and 177 female) were analyzed. Body mass index was 41.4±5.4 kg/m2 at baseline, declined to 33.8±5.8 kg/m2 12 months after surgery (P<.001), and further reduced to 31.9±5.1 kg/m2 36 months after surgery (P<.001 versus 12 months). Scores in the SF-36 subscales were lower than in the general Italian population at baseline. The physical component summary score was 51.9±11.6 at baseline, improved to 79.2±15.4 at 12 months (P<.001), and stabilized to 79.8±15.6 at 36 months. The mental summary score was 52.3±11.8 at baseline, improved to 75.2±17.3 at 12 months (P<.001), and stabilized to 74.2±17.5 at 36 months. A decline>10 points between 12 and 36 months in the summary scores was observed in 22.0% of the patients for PCS and in 26.8% for MCS. In a multiple linear regression analysis, deterioration in HR-QoL in the 12-36 months period was associated to the presence of better HR-QoL values at 12 months and to a more pronounced reduction of the self-perceived effect of the banding at 36 months. CONCLUSION Improvements in HR-QoL observed in the first year after surgery maintained up to the third year after gastric banding.