Reduced Lipopolysaccharide-Binding Protein (LBP) Levels Are Associated with Non-Alcoholic Fatty Liver Disease (NAFLD) and Adipose Inflammation in Human Obesity.

Lipopolysaccharide (LPS) and its binding protein LBP have emerged as potential contributors to the progression from overweight/obesity to overt metabolic diseases and NAFLD. While LPS is known to activate hepatocyte inflammation, thus contributing toward NAFLD development, the role of LBP is more intricate, and recent data have shown that experimental reduction in hepatic LBP promotes NAFLD progression. In this cross-sectional investigation, we evaluated circulating LBP in relation to obesity, NAFLD, visceral adipose tissue (VAT) inflammation, and type 2 diabetes (T2D). We recruited 186 individuals (M/F: 81/105; age: 47 ± 10.4 years; BMI: 35.5 ± 8.6 kg/m2); a subgroup (n = 81) underwent bariatric surgery with intra-operative VAT and liver biopsies. LBP levels were higher in obese individuals than non-obese individuals but were inversely correlated with the parameters of glucose metabolism. Reduced LBP predicted T2D independent of age, sex, and BMI (p < 0.001). LBP levels decreased across more severe stages of hepatosteatosis and lobular inflammation, and were inversely associated with VAT inflammation signatures. In conclusion, LBP levels are increased in obese individuals and are associated with a more favorable metabolic profile and lower NAFLD/NASH prevalence. A possible explanation for these findings is that hepatic LBP production may be triggered by chronic caloric excess and facilitate LPS degradation in the liver, thus protecting these individuals from the metabolic consequences of obesity.

Supraorbital Basosquamous Carcinoma Treated with Cemiplimab Followed by Sonidegib: A Case Report and Review of the Literature.

Basal cell carcinoma (BCC) is a skin cancer with low local aggressiveness and a low tendency to metastasize. Basosquamous Carcinoma (BSC) represents an aggressive histological subtype of BCC with intermediate features between Squamous Cell Carcinoma (SCC) and BCC. Cemiplimab is currently approved as first-line therapy in SCC and second-line therapy in BCC patients who have progressed on or are intolerant of a Hedgehog pathway Inhibitor (HHI). Our study describes the case of a 59-year-old man with BSC who was successfully treated with 5 cycles of Cemiplimab as first-line therapy and Sonidegib as second-line therapy. Currently, the efficacy of Cemiplimab against BSC and other histopathological subtypes of BCC has not been fully elucidated, as has the role of sequential or combination therapy with Cemiplimab and HHI in the management of BSC. The aim of this case report is to highlight the need to outline the use of checkpoint inhibitors in BCCs and focus attention on the synergistic role of Cemiplimab and HHIs in such a controversial entity as BSC.

Incidental papillary thyroid microcarcinoma in consecutive patients undergoing thyroid surgery for benign disease. A single center experience.

BACKGROUND: There has recently been an increase in the incidental histological diagnosis of papillary thyroid microcarcinoma (I-PTMC), that varies from 3.5% in autopsies studies, to 5.2% in thyroid specimens from thyroid surgery, up to 9.4% in patients from areas of endemic goiter. AIM: To evaluate the incidence and the histological characteristics of I-PTMC in patients undergoing thyroidectomy for benign thyroid diseases, and to evaluate sex, age, toxic and non-toxic goiter, Hashimoto's thyroiditis as potential risk factors. MATERIALS AND METHODS: Prospective observational study on 124 patients, median age 56.3±13.25sd range 24-80 years, 93(75%)F, 31(25%)M, with surgical indications for toxic and non-toxic uni/multinodular goiters, in pharmacological euthyroidism. An accurate histological examination (HE) of entirely embedding thyroid samples was performed to identify microscopic foci of I-PTCM. Logistic regression analysis of the abovementioned parameters was performed to identify the risk factors. RESULTS: Total incidence of I-PTMC was 15.3%(19/124), with F/M ratio 2:1. All I-PTMCs were intraparenchymal with an intact thyroid capsule; 68.5% were bilateral-multifocal, 21% unilateral-unifocal, 10.5% unilateral-multifocal; maximum diameter was <5mm in 57.9% and ≥5mm in 42.1%; 63.1% were follicular variant, 36.9% classical variant; intra-thyroid lymphatic invasion and lymph node infiltration of the central compartment and para-tracheal was found in the only patient with "tall-cell" classical variant. No risk factors was found. CONCLUSIONS: The incidence higher than that reported in the literature, is probably due to the accurate HE of entirely embedding thyroid samples, which is the most important tool to identify microscopic foci of I-PTCM. The highest reported rate of bilateral multifocality of the neoplasm recommend the total thyroidectomy as surgical treatment of choice, also in patients undergoing thyroid surgery for "presumptive" benign diseases. KEY WORDS: Benign Thyroid Disease, Incidental Papillary Thyroid Microcarcinoma, I-PTCM, Thyroid Surgery.

Neuropeptide Y Promotes Human M2 Macrophage Polarization and Enhances p62/SQSTM1-Dependent Autophagy and NRF2 Activation.

Neuropeptide Y (NPY) is an abundantly expressed peptide capable of modulating innate and adaptive immune responses and regulating chemotaxis and cytokine secretion by macrophages. Abnormal regulation of NPY is involved in the development of atherosclerosis. The inflammatory infiltrate within atherosclerotic plaque is characterized by accumulation of macrophages, which are subject to reprogram their phenotypes in response to environmental signals. Macrophage number and phenotype influence plaque fate. Here, we investigated the effect of NPY on the changes in phenotype and functions of human macrophages, from the pro-inflammatory phenotype M1 to the reparative M2, indicative of atherosclerosis regression or stabilization. Human monocytes were differentiated in vitro into macrophages with M-CSF (M0) and polarized towards an M1 phenotype with IFN-γ plus LPS M(IFN-γ/LPS) or M2 with IL-10 (M IL-10) and further challenged with NPY (10-7-10-9 M) for 8-36 h. Cell phenotype and functions were analyzed by immunofluorescence and immunochemical analyses. NPY affected macrophage surface markers and secretome profile expression, thus shifting macrophages toward an M2-like phenotype. NPY also prevented the impairment of endocytosis triggered by the oxysterol 7-keto-cholesterol (7KC) and prevented 7KC-induced foam cell formation by reducing the lipid droplet accumulation in M0 macrophages. NPY-treated M0 macrophages enhanced the autophagosome formation by upregulating the cell content of the autophagy markers LC3-II and p62-SQSTM1, increased activation of the anti-oxidative transcription factor NRF2 (NF-E2-related factor 2), and subsequently induced its target gene HMOX1 that encodes heme oxygenase-1. Our findings indicate that NPY has a cytoprotective effect with respect to the progression of the inflammatory pathway, both enhancing p62/SQSTM1-dependent autophagy and the NRF2-antioxidant signaling pathway in macrophages. NPY signaling may have a crucial role in tissue homeostasis in host inflammatory responses through the regulation of macrophage balance and functions within atherosclerosis.

Adipose tissue remodelling in obese subjects is a determinant of presence and severity of fatty liver disease.

AIMS: Experimental data suggest that visceral adipose tissue (VAT) dysfunction contributes to non-alcoholic fatty liver disease (NAFLD) development in obesity, however, data on humans are limited. Aims of this study were to investigate the relationship between NAFLD and VAT morphofunctional impairment and to determine whether the extent of VAT remodelling is associated with liver damage and metabolic alterations in obesity. METHODS: We analysed data from 40 obese individuals candidate to bariatric surgery in whom paired intraoperative liver and omental biopsies were performed for diagnosing NAFLD and VAT inflammation by immunohistochemistry and mRNA expression studies. RESULTS: Within our study population, NAFLD was significantly associated with greater VAT CD68+ macrophages infiltration (P = .04), fibrosis (P = .04) and impaired microvascular density (P = .03) as well as increased expression of markers of local hypoxia, apoptosis and inflammation (UNC5B, CASP7, HIF1-α, IL-8, MIP2, WISP-1, all P < .01). The degree of VAT inflammation correlated with the severity of hepatic injury (steatosis, inflammation, fibrosis; all P < .01) and impaired gluco-metabolic profile. CONCLUSIONS: In obese patients, NAFLD is associated in a dose-dependent manner with signs of VAT remodelling, which reflect more severe clinical metabolic impairment. Our study depicts morphological alterations and novel mediators of VAT dysfunction, adding knowledge for future therapeutic approaches to NAFLD and its metabolic complications.

Circulating dipeptidyl peptidase-4 is independently associated with the presence and severity of NAFLD/NASH in individuals with and without obesity and metabolic disease.

INTRODUCTION: Dipeptidyl peptidase 4 (DPP4) levels are associated to metabolic and cardiovascular diseases in humans; initial evidence reported a relationship between DPP4 and chronic liver diseases. Aim of this study was to investigate hepatic and systemic DPP4 levels/activity in relation to NAFLD/NASH in individuals with and without metabolic disease. METHODS: We recruited fifty-two obese individuals undergoing bariatric surgery and intra-operative liver biopsy at Sapienza University, Rome, Italy. The association between DPP4 levels/activity and NAFLD was also evaluated in 126 non-obese individuals recruited in the same setting. RESULTS: NAFLD patients had significantly higher circulating DPP4 activity than no-NAFLD in both the obese and non-obese cohorts; plasma DPP4 activity and levels linearly correlated with steatosis grade and inflammation at the liver biopsy. Hepatic DPP4 mRNA was not associated to either its circulating levels/activity or NAFLD. In the multivariate logistic regression analysis on all the study participants (n = 178), higher circulating DPP4 activity was associated with NAFLD independently of potential confounders with OR (95% CI): 3.5 (1.2-10.21), p = 0.022. CONCLUSIONS: This study demonstrates the coexistence of increased plasma DPP4 levels and activity in NAFLD. Circulating DPP4 measurement may represent a novel cost-effective strategy for NAFLD/NASH risk stratification and a potential tool for monitoring disease's progression in established NAFLD.

Granzyme B Expression in Visceral Adipose Tissue Associates With Local Inflammation and Glyco-Metabolic Alterations in Obesity.

Granzyme B (GrB) is a serine protease produced by immune and non-immune cells, able to promote multiple processes, like apoptosis, inflammation, extracellular matrix remodeling and fibrosis. GrB expression in visceral adipose tissue (VAT) was associated with tissue damage, local inflammation and insulin resistance in obesity murine model, but there is no data in humans. Aim of this study was to explore the expression of GrB in VAT from obese subjects in relation to adipose tissue injury, inflammation, metabolic alterations and GrB circulating levels. For this purpose, 85 obese individuals undergoing bariatric surgery and 35 healthy subjects (as control) were recruited at Sapienza University, Rome, Italy. Study participants underwent clinical work-up and routine biochemistry. mRNA expression of GrB in VAT and of a panel of VAT inflammatory markers was analyzed by real-time PCR. Serum GrB levels were measured by Elisa Affymetrix EBIO. We observed that 80% of obese patients expressed GrB mRNA in VAT, and GrB VAT expression was associated with the presence of local inflammation and glucose homeostasis alterations. Moreover, GrB serum levels, which were higher in obese subjects compared to non-obese healthy individuals, were associated with GrB expression in VAT and glyco-metabolic impairment. Our data show, for the first time in humans, that obese subjects with "sick" fat and altered glucose tolerance exhibit GrB expression in VAT, and suggest that GrB might contribute to obesity-related VAT inflammatory remodeling and glucose homeostasis dysregulation. Moreover, increased circulating GrB levels might represent a possible peripheral marker of VAT dysfunction in metabolic diseases.

Reduced Biliverdin Reductase-A Expression in Visceral Adipose Tissue is Associated with Adipocyte Dysfunction and NAFLD in Human Obesity.

Biliverdin reductase A (BVR-A) is an enzyme involved in the regulation of insulin signalling. Knockout (KO) mice for hepatic BVR-A, on a high-fat diet, develop more severe glucose impairment and hepato-steatosis than the wild type, whereas loss of adipocyte BVR-A is associated with increased visceral adipose tissue (VAT) inflammation and adipocyte size. However, BVR-A expression in human VAT has not been investigated. We evaluated BVR-A mRNA expression levels by real-time PCR in the intra-operative omental biopsy of 38 obese subjects and investigated the association with metabolic impairment, VAT dysfunction, and biopsy-proven non-alcoholic fatty liver disease (NAFLD). Individuals with lower VAT BVR-A mRNA levels had significantly greater VAT IL-8 and Caspase 3 expression than those with higher BVR-A. Lower VAT BVR-A mRNA levels were associated with an increased adipocytes' size. An association between lower VAT BVR-A expression and higher plasma gamma-glutamyl transpeptidase was also observed. Reduced VAT BVR-A was associated with NAFLD with an odds ratio of 1.38 (95% confidence interval: 1.02-1.9; χ2 test) and with AUROC = 0.89 (p = 0.002, 95% CI = 0.76-1.0). In conclusion, reduced BVR-A expression in omental adipose tissue is associated with VAT dysfunction and NAFLD, suggesting a possible involvement of BVR-A in the regulation of VAT homeostasis in presence of obesity.

Immunohistochemical detection of IL-17 and IL-23 improves the identification of patients with a possible diagnosis of Sjogren's syndrome.

OBJECTIVES: The diagnosis of primary Sjogren's syndrome (pSS) continues to be difficult and several patients keep symptomatic for years with different diagnoses before confirmation of pSS. Since the IL-23-IL-17 axis is involved in the etiopathogenesis of pSS we evaluated by immunohistochemistry and morphometric methods the presence of IL-17 as well as IL-23 within minor salivary glands (MSG) obtained from patients with uncertain diagnosis of pSS. MATERIALS AND METHODS: 42 patients, with symptoms attributable to pSS, and 8 patients used as a control, were enrolled for the study. Autoantibody detection, histological analysis for the presence of Germinal Centers (GC+), immunohistochemistry to detect IL-23 and IL-17 were performed. RESULTS: The detection of GC + anti-SSA and anti-SSB antibody in parallel with the detection of IL-17 and IL-23, displays only a diagnostic reinforcement value. Instead, the detection of a positive reaction for both IL-17 and IL-23 without GC + or autoantibody within minor salivary glands, as detected in 36 % of patients with uncertain diagnosis, may be hold as a sensitive and specific marker to identify those patients who are likely to evolve into pSS. CONCLUSION: we suggest to use the IL-17/ IL-23 immunohistochemical detection to improve the identification of patients with a possible diagnosis in all cases which do not fully meet the American-European criteria for pSS, in particular when the GC + are not present at histopathological analysis and anti-SSA and anti-SSB antibody are undetectable in the serum.

Relationship between hepatic and systemic angiopoietin-like 3, hepatic Vitamin D receptor expression and NAFLD in obesity.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide and an independent risk factor for cardiovascular mortality. Angiopoietin-like proteins (ANGPTLs) are targets for vitamin D receptor (VDR)-mediated gene transcription and this axis may promote NAFLD. ANGPTL3 is a hepatokine which inhibits lipoprotein lipase and its experimentally induced inactivation reduces hepatosteatosis. Little is known on ANGPTL3 in human NAFLD and no data exist on its relationship with hepatic VDR/VD-related genes. The aim of this research was to investigate hepatic ANGPTLs and VDR/VD-related gene expression in human obesity in relation to NAFLD. METHODS: We conducted a cross-sectional investigation on forty obese subjects with/without NAFLD. We evaluated hepatic ANGPTL3, ANGPTL4, ANGPTL8, LPL, VDR, CYP27A1 and CYP2R1 mRNA expression in liver biopsies by RT-PCR; VDR expression was further investigated by immunohistochemistry; circulating ANGPTL3 was measured by Milliplex assay. RESULTS: Compared to non-NAFLD, NAFLD individuals had significantly higher hepatic VDR, ANGPTL3 and LPL expression. ANGPTL3 correlated with steatosis grade, LPL, VDR, CYP27A1 and CYP2R1 expression. Plasma ANGPTL3 concentrations were positively associated with clinical/histological markers of NAFLD/NASH and with hepatic ANGPTL3 expression. Greater hepatic VDR expression was the main determinant of hepatic ANGPTL3 after adjusting for multiple confounders. CONCLUSIONS: Hepatic ANGPTL3 expression correlates with greater VDR expression, presence and severity of NAFLD and translates in increased circulating ANGPTL3, likely as a result of its modulation by up-regulated hepatic VDR in NAFLD. This study provides novel insights to potential mechanisms underlying ANGPTLs-mediated ectopic fat accumulation and NAFLD development in obesity.

Non-antibiotic prophylaxis in thyroid surgery. Experience of a single Institution and revision of literature.

AIM: To evaluate the incidence of SSI and systemic infectious complications in a consecutive series of patients undergoing thyroid surgery in the absence of prophylactic antibiotic (NO-AP). METHODS: Prospective observational study including 77 patients who underwent total thyroidectomy and completion of previous hemithyroidectomy in NO-AP. The surgical intervention was performed by surgeons who were experienced in the procedure, and involved the use of Ligasure Harmonic Ethicon®, absorbable hemostat in oxidized regenerated cellulose (Tabotamp®), and skin incision suture device Skin Stapler®. The following risk factors were assessed: gender, age, BMI, alcohol consumption, habitual smoking, co-morbidities, ASA score, indication to surgery, duration of anesthesia and procedure lenght, type of surgical procedure, fever, white blood cells count, dosage of the pre-operative C Reactive Protein in the five first post-operative day, and histological diagnosis. The data were collected and processed using IBM SPSS software v.23.0. RESULTS: No factors of increased infectious risk have been identified. No infectious surgical and systemic complications have been reported causes of prolongation of the length of the hospital stay. CONCLUSIONS: Fever, neutrophilic leukocytosis and increased PCR cannot be assessed as predictive factors of infectious complication in thyroid surgery. The cutaneous antisepsis of the operative field with chlorhexidine gluconate, the improvement of the surgical technique, the protection of the cutaneous margins of incision, the use of new devices, the accurate hemostasis and the reduction of surgery time lead to a lack of SSIs and systemic infection complications in all patients undergoing thyroid surgery in NO-AP. KEY WORDS: Antibiotic prophylaxis, Surgical site infections, Thyroid surgery, Thyroidectomy.

Insulin resistance, but not insulin response, during oral glucose tolerance test (OGTT) is associated to worse histological outcome in obese NAFLD.

BACKGROUND AND AIM: Obese subjects are at high risk of nonalcoholic fatty liver disease (NAFLD) and diabetes (T2D) due to insulin resistance (IR). Since high glucose levels are as toxic as lipids for hepatic metabolism, we hypothesize that altered response to oral glucose tolerance test (OGTT) is associated to more severe NAFLD with significant/advanced liver damage. METHODS AND RESULTS: We studied 90 subjects with morbid obesity (73F/17M, BMI = 43.2 ± 5,9 kg/m2) undergoing bariatric surgery and intraoperative liver biopsy, and measured HbA1c, HOMA-IR (fasting Glucose x Insulin/22.5), OGTT glucose and insulin profile, and calculated OGIS (muscle insulin sensitivity), hepatic-IR (glucose [AUC0-30] x insulin [AUC0-30]) during OGTT, insulin response as (insulin [dAUC0-120]/glucose [dAUC0-120] or Insulinogenic Index (IGI = (I30-I0)/(G30-G0)). Patients were divided in 3 groups according to liver biopsy: A (no-NAFLD, 23%), B (simple steatosis (SS), 53%) and C (NASH, 24%) with similar age, gender and BMI. Diabetes was 0% in no-NAFLD, 13% in SS, 35% in NASH. During OGTT, OGIS decreased from A to C (422 vs 360 vs 338, p < 0.01). Increased insulin concentrations, HbA1c, HOMA-IR and OGIS, not Hep-IR, were strongly associated to hepatic steatosis (p = 0.03, p = 0.0001 and p = 0.01 respectively). Hepatic fibrosis stage was mild as most of the patients had fibrosis grade-1 (69% vs. 8% no fibrosis) and associated to fasting insulin, HbA1c and HOMA-IR. dAUC-I/dAUC-G was similar in the 3 groups, while only AUC-I was strongly associated to steatosis (r = 0.35, p = 0.005), but not to fibrosis. CONCLUSIONS: In morbid obesity indexes of IR, and not of insulin response, are markers of histological severity of liver disease.

Noninvasive assessment of hepatic steatosis and fibrosis in patients with severe obesity.

PURPOSE: In morbid obesity nonalcoholic fatty liver disease (NAFLD) is endemic. Aim of this study is to evaluate the diagnostic accuracy of the most common noninvasive methods for identify NAFLD and fibrosis in a cohort of morbid obese population. METHODS: Ninety morbid obese patients undergoing bariatric surgery (BS) and intraoperative liver biopsy were evaluated preoperatively with Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and serum biomarkers for steatosis and fibrosis and liver stiffness measurement (LSM) using acoustic radiation force impulse (ARFI) elastography. All nondiabetic patient (n = 77) underwent OGTT and calculation of Oral Glucose Insulin Sensitivity index (OGIS). RESULTS: In the entire cohort prevalence of NAFLD was 77%, NASH 24%, moderate/severe steatosis 50%, and significant fibrosis 14%. New cut-offs were evaluated for all steatosis score assessed in this population. In all patients with moderate/severe steatosis HOMA IR was significantly greater than 3.5. ALT, GGT, Triglycerides, HOMA IR, and ARFI increased with fibrosis grade (p 0.03, p 0.008, p 0.04, p 0.05, respectively) and AST to Platelet ratio (APRI) was the only noninvasive fibrosis score significantly increased in significant fibrosis (p 0.04). A combination of 1/OGIS and VAI was able to discriminate NASH from simple steatosis (NAFL) (p 0.02). CONCLUSIONS: In morbid obese subjects, we calculated new cut-offs of the most common steatosis indexes and found that a score based on insulin resistance (1/OGIS) and abdominal obesity (VAI) could represent a way to identify morbid obese subjects at risk of NASH.

Predictive markers of long-term recurrence in chronic rhinosinusitis with nasal polyps.

BACKGROUND: In last years, many attempts were made to recognize chronic rhinosinusitis with nasal polyps (CRSwNP) phenotypes focusing on identifying relevant key pathogenic molecules. Polyps recurrence rate ranges from 4% to 60%, so it's clear that not all clinical and immunologic factors associated with recurrence are known. OBJECTIVE: We investigate the inflammatory profile in patients with long term recurrent and non-recurrent CRSwNPs and if a specific profile is associated with recurrence, comparing eosinophilic, neutrophilic and lymphocytic infiltration, as well as IL-5 and IL-8 expression to long term recurrence rate. METHODS: This prospective study included 44 adult patients with CRSwNP treated with endoscopic sinus surgery between 2008 and 2010. Long term follow-up data (8-10 years) indicated that among 44 patients, 18 (40.1%) experienced long term recurrence of nasal polyposis needing maximal medical treatment or revision surgery. We realized two groups: one with patients who didn't present long term recurrence (26 patients) and another with patients who presented long term recurrence (18 patients) and in both groups eosinophilic, neutrophilic and lymphocytic infiltration and IL-5 and IL-8 expression were measured. RESULTS: The parameters that reached statistical significance (p < 0.05) comparing the two groups were eosinophilic infiltration and IL-5 expression, whereas neutrophilic and lymphocytic infiltration, as IL-8 expression didn't show any significant difference. Asthma and aspirin intolerance seemed significantly more frequent in patients with recurrence, while allergy presented not statistically significant difference between two groups. CONCLUSIONS: We can conclude that high eosinophilic infiltration and high IL-5 expression in CRSwNP correlate with higher rate of long term recurrence, while neutrophilic and lymphocytic infiltration, and IL-8 expression don't correlate with it. These findings provide the opportunity to improve our ability to predict the prognosis of surgical intervention, although it is still needed to explore the optimal predictor of outcome in CRSwNP.

Polypoid lesions of the gallbladder in a consecutive series of 2631 patients. A single-center experience.

BACKGROUND: Challenges in the diagnosis of polypoid gallbladder lesion (PLG) is due to the low sensibility (SE) of ultrasound scan (US), and the selection criteria of patients with PLG to be addressed to surgical treatment or followup are not yet fully defined. MATERIALS AND METHODS: Retrospective observational study was conducted on 2631 patients, 1175(44.6%) M, mean age 56 years, 1456(55.4%) F, mean age 46 years, who underwent laparoscopic and open cholecystectomy. RESULTS: The US diagnosis for PLG was placed in 38/2631(1.4%) patients. On histological examination (HE) the polyps were identified in 68/2631(2.6%) patients and it was associated with biliary lithiasis in 28/2631 (1.1%) cases. From the US and HE comparison, the ultrasound diagnosis was burdened by false positives (8/38; 21%) and false negatives (38/2631;1.45%), with SE 44% (95% c.i.:32.2-55.7). The histological incidence of gall bladder cancer (GBC) was 0.38%(10/2631). DISCUSSION: US survey underestimated the incidence of PLG compared to the histological finding (p=0.021). Female gender has been shown to be a specific risk factor for benign and malignant PLG and non-polypoid mucosal lesions (p=0.041). The parietal lesion size <0.5cm does not exclude the neoplastic nature. Currently the prevention and diagnosis of GBC is based on the early detection and treatment of potentially evolutionary polypoid lesions over a period of about 15 years. CONCLUSIONS: It is probably that early cholecystectomy in all the patients with PLG of diameter <1cm, isolated or associated with lithiasis, symptomatic and asymptomatic, can contribute to the reduction of the incidence of GBC. KEY WORDS: Cholecystectomy, Gallbladder polyps, Gallbladder cancer, Ultrasound scan.

KMT2C modulates migration and invasion processes in osteosarcoma cell lines.

In this study we investigated the role of KMT2C (a chromatin-modifying and remodelling protein) in osteosarcoma progression through cell migration and invasion assays in osteosarcoma primary and metastatic cell lines. Wound healing and transwell assays were used to detect changes of cell migration and matrigel assay was used to evaluate changes of cell invasion in primary and metastatic osteosarcoma cell lines after KMT2C siRNA transfection. We found that primary osteosarcoma cell lines showed the highest capacity of migration before mRNA KMT2C silencing and the highest capacity of invasion after mRNA KMT2C silencing; on the contrary, osteosarcoma metastatic cell line showed the highest capacity of migration after mRNA KMT2C silencing and the highest capacity of invasion before mRNA KMT2C silencing. Our study supports data in favour of selective enhancer changes, KMT2C-mediated, in metastatic osteosarcoma probably due to the different microenvironment between primary and metastatic sites.