The clinical impact of an extra virgin olive oil enriched mediterranean diet on metabolic syndrome: Lights and shadows of a nutraceutical approach.

For years it has been established that the only truly effective treatment of metabolic syndrome (MS) is lifestyle modification to prevent its cardiovascular (e.g., coronary artery disease and atherosclerosis), metabolic (e.g., diabetes mellitus), and hepatic (e.g., steatosis and non-alcoholic steatohepatitis) complications. The focal points of this approach are to increase physical activity and intake of a diet characterized by high quantities of fruits, vegetables, grains, fish, and low-fat dairy products, the so called mediterranean diet (MD); however, the added value of MD is the presence of extra virgin olive oil (EVOO), a healthy food with a high content of monounsaturated fatty acids, especially oleic acid, and variable concentrations (range 50-800 mg/kg) of phenols (oleuropein, ligstroside, and oleocanthal, and their derivatives, phenolic alcohols, such as hydroxytyrosol and tyrosol). Phenolic compounds not only determine EVOO's main organoleptic qualities (oxidative stability, specific flavor, and taste features) but, theoretically, make it a source of antioxidant, anti-inflammatory, insulin-sensitizing, cardioprotective, antiatherogenic, neuroprotective, immunomodulatory, and anticancer activity. Although many studies have been carried out on EVOO's clinical effects and attention toward this dietary approach (healthy and palatable food with strong nutraceutical activity) has become increasingly pressing, there are still many dark sides to be clarified, both in terms of actual clinical efficacy and biochemical and molecular activity. Thus, we reviewed the international literature, trying to show the state of the art about EVOO's clinical properties to treat MS (along with correlated complications) and the future prospective of its nutraceutical use.

SGLT2 Inhibitors as the Most Promising Influencers on the Outcome of Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD), the most frequent liver disease in the Western world, is a common hepatic manifestation of metabolic syndrome (MetS). A specific cure has not yet been identified, and its treatment is currently based on risk factor therapy. Given that the initial accumulation of triglycerides in the liver parenchyma, in the presence of inflammatory processes, mitochondrial dysfunction, lipotoxicity, glucotoxicity, and oxidative stress, can evolve into non-alcoholic steatohepatitis (NASH). The main goal is to identify the factors contributing to this evolution because, once established, untreated NASH can progress through fibrosis to cirrhosis and, ultimately, be complicated by hepatocellular carcinoma (HCC). Several drugs have been tested in clinical trials for use as specific therapy for NAFLD; most of them are molecules used to cure type 2 diabetes mellitus (T2DM), which is one of the main risk factors for NAFLD. Among the most studied is pioglitazone, either alone or in combination with vitamin E, glucagon-like peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors. Actually, the most promising category seems to be sodium-glucose cotransporter (SGLT2) inhibitors. Their action is carried out by inhibiting glucose reabsorption in the proximal renal tubule, leading to its increased excretion in urine and decreased levels in plasma. Experimental studies in animal models have suggested that SGLT2 inhibitors may have beneficial modulatory effects on NAFLD/NASH, and several trials in patients have proven their beneficial effects on liver enzymes, BMI, blood lipids, blood glucose, and insulin resistance in NAFLD patients, thus creating strong expectations for their possible use in preventing the evolution of liver damage in these patients. We will review the main pathogenetic mechanisms, diagnostic modalities, and recent therapies of NAFLD, with particular attention to the use of SGLT2 inhibitors.

Perioperative Management of Pheochromocytoma: From a Dogmatic to a Tailored Approach.

BACKGROUND: Perioperative management of pheochromocytoma (PCC) remains under debate. METHODS: A bicentric retrospective study was conducted, including all patients who underwent laparoscopic adrenalectomy for PCC from 2000 to 2017. Patients were divided into two groups: Group 1 treated with alpha-blockade, and Group 2, without alfa-blockers. The primary end point was the major complication rate. The secondary end points were: the need for advanced intra-operative hemostasis, the admission to the intensive care unit (ICU), the length of stay (LOS), systolic (SBP), and diastolic blood pressure (DBP). Univariate and multivariate analysis was conducted. A p-value < 0.05 was considered statistically significant. RESULTS: Major postoperative complications were similar (p = 0.49). Advanced hemostatic agents were 44.9% in Group 1 and 100% in Group 2 (p < 0.001). In Group 2, no patients were admitted to the ICU, while only 73.5% of Group 1 (p < 0.001) were admitted. The median length of stay was larger in Group 1 than in Group 2 (p = 0.026). At the induction, SBP was 130 mmHg in Group 1, and 115 mmHg (p < 0.001). The pre-surgery treatment was the only almost statistically significant variable at the multivariate analysis of DBP at the end of surgery. CONCLUSION: The preoperative use of alfa-blockers should be considered not a dogma in PCC.

Gut Microbiota, Obesity and Bariatric Surgery: Current Knowledge and Future Perspectives.

BACKGROUND: There is an urgent need for a better understanding and management of obesity and obesity- associated diseases. It is known that obesity is associated with structural and functional changes in the microbiome. METHODS: The purpose of this review is to present current evidence from animal and human studies, demonstrating the effects and the potential efficacy of microbiota modulation in improving obesity and associated metabolic dysfunctions. RESULTS: This review discusses possible mechanisms linking gut microbiota dysbiosis and obesity, since there is a dual interaction between the two of them. Furthermore, comments on bariatric surgery, as a favourable model to understand the underlying metabolic and inflammatory effects, as well as its association with changes in the composition of the gut microbiota, are included. Also, a possible impact of anti-obesity drugs and the novel antidiabetic drugs on the gut microbiota has been briefly discussed. CONCLUSION: More research is needed to better understand here discussed the association between microbiota modulation and obesity. It is expected that research in this field, in the following years, will lead to a personalized therapeutic approach considering the patient's microbiome, and also give rise to the discovery of new drugs and/or the combination therapies for the management of obesity and obesity-related co-morbidities.

Laparoscopic adrenalectomy: preoperative data, surgical technique and clinical outcomes.

BACKGROUND: laparoscopic adrenalectomy has become the standard treatment for adrenal lesions. The better clinical outcoms of laparoscopic technique are valid for treatment of small benign masses (< 5-6 cm), instead there are still open questions in literature regarding the correct management of larger lesions (> 6 cm) or in case of potentially malignant adrenal tumors. The aim of this study is to evaluate the outcomes of laparoscopic adrenalectomy in a referral surgical department for endocrine surgery. METHODS: at the University Hospital Policlinico "P. Giaccone" of Palermo between January 2010 and December 2017 we performed a total of 81 laparoscopic adrenalectomy. We created a retrospective database with analysis of patients data, morphologic and hormonal characteristics of adrenal lesions, surgical procedures and postoperative results with histological diagnosis and complications. RESULTS: Mean size of adrenal neoplasm was 7,5 cm (range 1.5 to 18 cm). The mean operative time was 145 min (range 75-240). In statistical analysis lenght of surgery was correlated to the lesion diameter (p < 0.05) but not with pre-operative features or histological results. 5 intraoperative complications occurred. Among these patients 4 presented bleeding and 1 a diaphagmatic lesion. No conversion to open surgery was necessary and no intraoperative blood transfusion were required. Mean estimated blood loss was 95 ml (range 50-350). There was no capsular disruption during adrenal dissection. Mean length of hospital stay was 3.7 days (range 3-6 days). CONCLUSIONS: Laparoscopic adrenalectomy is a safe procedure with low rate of morbidity. An accurate preoperative radiological examination is fundamental to obtain a stringent patients selection. The lesion diameter is related to longer operative time and appeares as the main predictive parameter of intraoperative complications but these results are not statistically significant. On the other side secreting adrenal tumors require more attention in operative management without increased rate of postoperative complications.

Innovation in endocrine surgery: robotic versus laparoscopic adrenalectomy. Meta-analysis and systematic literature review.

Several studies in the last years demonstrated the better surgical outcome of laparoscopic approach to adrenal gland. Laparoscopic surgery is more difficult to learn and requires different psychomotor skills than open surgery, especially with regard to complex maneuvers requiring precision and dexterity. The development of robotic platform with three-dimensional vision and increased degrees of freedom of the surgical instruments has the aim to overcome these problems. We performed a systematic literature review with meta-analysis to evaluate preoperative data and surgical outcomes of robotic adrenalectomy compared with laparoscopic technique. In September 2016 we performed a systematic literature review using the Pubmed, Scopus and ISI web of knowledge database with search term "robotic adrenalectomy". We identified 13 studies with eligible criteria that compared surgical outcomes. This present systematic review with meta-analysis includes 798 patients: 379 underwent to robotic adrenalectomy (cases group) and 419 to laparoscopic adrenalectomy (controls group). There were no significant differences between the two groups of patients respect to age, gender, laterality and tumor size. BMI instead was significant lower in the robotic group. In this group we found also patients with higher incidence of previous abdominal surgery. The results from operative time demonstrated lower operative time for laparoscopic group but there were no significant differences with robotic group. Robotic adrenalectomy showed a significant lower blood loss. Robotic adrenalectomy is a safe and feasible technique with reduced blood loss and shorter hospital stay than laparoscopic adrenalectomy. Laparoscopic approach seems to be a more rapid technique when comparing to robotic technique, although recent studies demonstrate a significant operative time reduction in robotic group with the learning curve improvement and the development of new surgical technology.

Three-dimensional (3D) versus two-dimensional (2D) laparoscopic adrenalectomy: A case-control study.

INTRODUCTION: Laparoscopic adrenalectomy is today considered the gold standard of treatment for adrenal tumors. The development of high definition cameras does not eliminate the major limitation of two-dimensional (2D) laparoscopy: lack of depth perception and loss of spatial orientation. Tree-dimensional (3D) HD laparoscopy was developed as an alternative to conventional 2D laparoscopy. METHODS: We report our experience with use of 3D vision system for laparoscopic adrenalectomy. Between January 2009 and March 2015 we performed a total of 52 laparoscopic adrenalectomies. In this case-control study we considered 13 laparoscopic adrenalectomies performed with three-dimensional (3D) vision system as case group. The last 26 procedures made with two-dimensional (2D) HD laparoscopic system represented the control group. We considered primary end-points: operative time, intraoperative complications and conversion rate. We evaluated also quality of depth perception and surgical strain. RESULTS: Although the operative time for the entire surgical procedure was shorter in 3D group, there were no significant differences. The surgeon experienced better depth perception with 3D system and subjectively reported less strain using 3D vision system. Residents and medical students confirmed these data on surgical outcome. CONCLUSION: 3D system vision does not seem to influence the operative time of laparoscopic adrenalectomy performed by experienced surgeon because the surgical technique request simple tasks. We obtain the better visualization in depth perception with effect on surgical precision. Comparative studies are necessary to verify if 3D can reduce perioperative complication with similar operative time.

Neck lymph nodes in chronic autoimmune thyroiditis: the sonographic pattern.

BACKGROUND: Neck lymph nodes may be involved in the pathogenesis of chronic autoimmune thyroiditis (CAT). This study was undertaken to identify which of the sonographic features of cervical lymph nodes are readily applicable to patients affected by CAT compared to healthy control subjects. METHODS: We recruited 106 patients (92 females and 14 males) with CAT and 70 control subjects (53 females and 17 males) without clinical, biochemical, and ultrasonographic evidence of thyroid and neck diseases. We performed laboratory tests (thyrotropin, antithyroperoxidase antibodies, antithyroglobulin antibodies, and ultrasonography) to evaluate in each group: (i) thyroid function, autoimmunity, and morphology; (ii) number, topographic distribution (levels I-VI), and morphology of neck nodes (long-axis diameter; short-axis diameter; short-axis/long-axis ratio; absence or presence of hilus). RESULTS: Total number of neck nodes with long-axis diameter >10 mm was significantly higher in the CAT group than in the control group (mean±standard deviation [SD]: 3.7±2.4 vs. 0.8±1.3; p<0.001) with significantly increased differences in levels II (1.4±0.8 vs. 0.3±0.5; p<0.001), III (2±1.2 vs. 0.3±0.7; p<0.001), and IV (0.7±0.7 vs. 0.07±0.2; p<0.001). More nodes with a hilus were found in the CAT group than in the control group (mean number of nodes±SD: 2.8±1.9 vs. 0.7±1.1; p<0.001). Short-axis diameter of level III (4.4±1 vs. 3.7±1.2 mm; p=0.002) and level IV nodes (3.9±1 vs. 3.1±0.5 mm p=0.030) was increased in CAT patients when compared with healthy controls. CONCLUSIONS: The present study is the first one aiming at a systematic description of the sonographic pattern of cervical lymph nodes in CAT. An increased number of benign hyperplastic neck nodes, especially in levels II-IV, appears to be a characteristic sonographic finding associated with CAT.

In vitro generation of pancreatic endocrine cells from human adult fibroblast-like limbal stem cells.

Stem cells might provide unlimited supply of transplantable cells for ß-cell replacement therapy in diabetes. The human limbus is a highly specialized region hosting a well-recognized population of epithelial stem cells, which sustain the continuous renewal of the cornea, and the recently identified stromal fibroblast-like stem cells (f-LSCs), with apparent broader plasticity. However, the lack of specific molecular markers for the identification of the multipotent limbal subpopulation has so far limited the investigation of their differentiation potential. In this study we show that the human limbus contains uncommitted cells that could be potentially harnessed for the treatment of diabetes. Fourteen limbal biopsies were obtained from patients undergoing surgery for ocular diseases not involving the conjunctiva or corneal surface. We identified a subpopulation of f-LSCs characterized by robust proliferative capacity, expressing several pluripotent stem cell markers and exhibiting self-renewal ability. We then demonstrated the potential of f-LSCs to differentiate in vitro into functional insulin-secreting cells by developing a four-step differentiation protocol that efficiently directed f-LSCs towards the pancreatic endocrine cell fate. The expression of specific endodermal, pancreatic, islet, and ß-cell markers, as well as functional properties of f-LSC-derived insulin-producing cells, were evaluated during differentiation. With our stage-specific approach, up to 77% of f-LSCs eventually differentiated into cells expressing insulin (also assessed as C-peptide) and exhibited phenotypic features of mature ß-cells, such as expression of critical transcription factors and presence of secretory granules. Although insulin content was about 160-fold lower than what observed in adult islets, differentiated cells processed ∼98% of their proinsulin content, similar to mature ß-cells. Moreover, they responded in vitro in a regulated manner to multiple secretory stimuli, including glucose. In conclusion, f-LSCs represent a possible relevant source of autologous, transplantable, insulin-producing cells that could be tested for the reversal of diabetes.

Fine-needle aspiration molecular analysis for the diagnosis of papillary thyroid carcinoma through BRAF V600E mutation and RET/PTC rearrangement.

OBJECTIVE: To evaluate BRAF(V600E) mutation on consecutive fine-needle aspiration biopsy (FNAB) specimens in order to assess FNAB's usefulness in preoperative papillary thyroid carcinoma (PTC) diagnosis with the contemporaneous analysis of RET/PTC1 and RET/PTC3 rearrangements obtained from ex vivo thyroid nodules. DESIGN: Thyroid FNABs from 156 subjects with nodules and 49 corresponding surgical samples were examined for the presence of BRAF mutation by real-time allele-specific polymerase chain reaction, confirmed with the use of a laser pressure catapulting system. Samples were also examined for RET/PTC rearrangements. The results were compared with the cytological diagnosis and histopathology. MAIN OUTCOMES: 13/156 cytological examinations were diagnostic for PTC and 19/156 showed suspicious/indeterminate FNAB (12.2%). FNAB-BRAF(V600E) mutation was detected in 11/16 (69%) cases with histological confirmation of PTC. In our series, RET/PTC rearrangement was detected in only one case of PTC, whereas it was not present in any case of adenoma, goiter, or Hashimoto's thyroiditis. No PTC case was found positive at the same time for BRAF mutation and RET/PTC rearrangements. CONCLUSION: BRAF(V600E) mutation detected on FNAB specimens, more than RET/PTC rearrangements, is highly specific for PTC and its routine research might well be an adjunctive and integrative diagnostic tool for the preoperative diagnostic iter.