CK2 modulates adipocyte insulin-signaling and is up-regulated in human obesity

Insulin plays a major role in glucose metabolism and insulin-signaling defects are present in obesity and diabetes. CK2 is a pleiotropic protein kinase implicated in fundamental cellular pathways and abnormally elevated in tumors. Here we report that in human and murine adipocytes CK2-inhibition decreases the insulin-induced glucose-uptake by counteracting Akt-signaling and GLUT4-translocation to the plasma membrane. In mice CK2 acts on insulin-signaling in adipose tissue, liver and skeletal muscle and its acute inhibition impairs glucose tolerance. Notably, CK2 protein-level and activity are greatly up-regulated in white adipose tissue from ob/ob and db/db mice as well as from obese patients, regardless the severity of their insulin-resistance and the presence of pre-diabetes or overt type 2 diabetes. Weight loss obtained by both bariatric surgery or hypocaloric diet reverts CK2 hyper-activation to normal level. Our data suggest a central role of CK2 in insulin-sensitivity, glucose homeostasis and adipose tissue remodeling. CK2 up-regulation is identified as a hallmark of adipose tissue pathological expansion, suggesting a new potential therapeutic target for human obesity

SCCA-IgM as a Potential Biomarker of Non-Alcoholic Fatty Liver Disease in Patients with Obesity, Prediabetes and Diabetes Undergoing Sleeve Gastrectomy

Background: Non-alcoholic fatty liver disease (NAFLD) has a high prevalence in obesity and its presence should be screened. Laparoscopic sleeve gastrectomy (LSG) is an effective treatment for obesity, but its effects on NAFLD are still to be firmly established. The diagnosis of non-alcoholic steatohepatitis (NASH) is currently performed by liver biopsy, a costly and invasive procedure. Squamous cell carcinoma antigen-IgM (SCCA-IgM) is a biomarker of viral hepatitis to hepatocellular carcinoma development and its role in NAFLD to NASH progression has not yet been investigated. Objective: The aim of this study was to evaluate SCCA-IgM as a non-invasive biomarker of NAFLD/NASH in patients with different degrees of metabolic-complicated obesity before and after LSG. Method: Fifty-six patients with obesity were studied before and 12 months after LSG; anthropometric, biochemical, clinical, and imaging data were collected. Results: At baseline steatosis was strongly associated with the glycaemic profile (p = 0.016) and was already present in prediabetic patients with obesity (82%). Only 3 patients had an SCCA-IgM level above the normal cut-off. SCCA-IgM titre did not change according to glycaemic profile or steatosis. Metabolic and inflammatory factors and transaminases significantly reduced after LSG-induced weight loss, except for SCCA-IgM. The ALT/AST ratio decreased post-LSG correlated with BMI (r = 0.297, p = 0.031), insulin (r = 0.354, p = 0.014), and triglycerides (r = 0.355, p = 0.009) reduction. Conclusions: Our results confirm the tight link between NAFLD and metabolic complications, suggesting prediabetes as a new risk factor of steatosis. SCCA-IgM does not seem to have a role in the identification and prognosis of NAFLD

Seric profile predictive for recurrence in patients undergone curative hepatic resection for metastasis from Colo-Rectal Carcinoma

Introduction: Liver metastatic disease is the first cause of death in Colorectal Cancer. Specifically, 20-25 % of patients has metastatic disease at the time of diagnosis, while 25-30 % of individuals will develop liver metastases during the course of disease. At diagnosis only 10-20% of patients is resectable remaining surgical resection the only potentially curative treatment. However, two-third of patients who received curative surgery will experience recurrence of disease, and 75% will relapse within the first two years after hepatectomy. Several combinations of clinical-pathological parameters have been proposed to analyze the prognosis of patients with potentially resectable colorectal liver metastases, in particular various molecular markers have been considered, but any of these has not been validated for clinical use. Recently, some trials have proposed the detection of tumoral circulating DNA to be a prognostic marker in solid neoplasms. Aim of the Study: Aim of the study is to determine if peri-operative tumoral circulating DNA detected in blood of patients with colorectal liver metastases can be a prognostic marker for recurrences. Materials and Methods: Between March 2009 and March 2011 we analyzed 26 patients who underwent surgical resection for colorectal liver metastases. 19 patients were male, 7 patients were female. Mean age was 63.7 years (45-79). We collected a sample of venous blood before surgical procedure (Tf0) and after 30 days (Tf1). In these two samples we applied qRT- PCR to quantify total circulating DNA (ALU83) and tumoral circulating DNA (ALU244) in serum. Results: Median follow-up was 15 months (range 3-26); median DFS was 19 months. Median ALU244/ALU83 ratio was 0.28 (range 0.0652-0.763). Patients with ALU244/ALU83 ratio > 0.28 had worst recurrence-free survival than patients with ALU244/ALU83 ratio 0.28. (Hazard Ratio 8.07; P-value: 0.0205). Conclusions: In our Study the value of circulating DNA ALU244/ALU83 ratio in patients with colorectal liver metastases who underwent curative hepatic resection has a prognostic value for detecting recurrences. It is necessary to enforce the case-study by increasing the number of patients and extending follow-up for patients already included.Introduzione: Nella storia naturale del cancro del colon–retto le metastasi epatiche costituiscono la causa maggiore di decesso. Il 20-25% dei pazienti presenta metastasi epatiche al momento della diagnosi del tumore primitivo mentre il 25-30% dei casi le svilupperà nel corso dell’evoluzione della malattia. Al momento della diagnosi solo il 10-20% di pazienti risulta candidato ad una resezione curativa del fegato pur rimanendo l’intervento chirurgico di resezione epatica l’unico trattamento potenzialmente curativo. Circa due terzi dei pazienti trattati con intento curativo va incontro a recidiva e il 75% di queste recidive si manifesta nei primi 2 anni dall’intervento chirurgico. Allo scopo di analizzare più accuratamente l'evoluzione clinica di questi pazienti sono stati considerati diversi fattori prognostici, in particolare è stato studiato l’andamento di molteplici marcatori molecolari, ma nessuno di questi è stato validato nella pratica clinica. Recentemente alcuni ricercatori hanno proposto lo studio del DNA circolante di origine tumorale come fattore prognostico in alcuni tumori solidi. Scopo dello Studio: Lo scopo dello studio è stato di verificare se la quantità di DNA circolante di origine tumorale misurata nel sangue dei pazienti prima e a 30 giorni dalla resezione epatica possa essere considerato un fattore prognostico di rischio di recidiva. Materiali e Metodi: Sono stati analizzati 26 pazienti sottoposti a resezione epatica per metastasi da cancro del colon-retto nel periodo compreso tra Marzo 2009 e Marzo 2011. 19 erano di sesso maschile e 7 di sesso femminile; l’età media è risultata di 63.7 anni (range 45-79). E’ stato effettuato un prelievo di sangue venoso prima dell’intervento (Tf0) e dopo 30 giorni dallo stesso (Tf1). In queste due serie di campioni è stata quantificata nel siero la quota di DNA circolante totale (ALU83) e la quota di DNA circolante di origine tumorale (ALU244).La quantificazione del DNA circolante è stata effettuata mediante mediante la q RT-PCR. Risultati: Il follow-up mediano di questi pazienti è risultato di 15 mesi (range 3-26); l’intervallo libero da malattia (DFS) mediano è risultato di 19 mesi Il valore mediano di ALU244/ALU83 è risultato pari a 0,28 (range 0.0652-0.763) Nei pazienti con rapporto ALU244/ALU83 > 0,28 l’hazard ratio di recidiva nei 12 mesi successivi all’intervento è risultato 8 volte superiore rispetto ai pazienti con rapporto ALU244/ALU83 0.28. (P- value: 0.0205). Conclusioni: Nel nostro studio il valore del rapporto ALU244/ALU83 del DNA circolante tumorale nei pazienti affetti da metastasi epatiche da cancro del colon-retto e sottoposti a resezione curativa del fegato è correlato con un elevato rischio di recidiva. Sarà indispensabile aumentare il follow-up di questo gruppo di pazienti ed implementare la casistica allo scopo di confermare i dati ottenuti

Mechanical Behavior of Subcutaneous and Visceral Abdominal Adipose Tissue in Patients with Obesity

The mechanical characterization of adipose tissues is important for various medical purposes, including plastic surgery and biomechanical applications, such as computational human body models for the simulation of surgical procedures or injury prediction, for example, in the evaluation of vehicle crashworthiness. In this context, the measurement of human subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) mechanical properties in relation to subject characteristics may be really relevant. The aim of this work was to properly characterize the mechanical response of adipose tissues in patients with obesity. Then, the data were exploited to develop a reliable finite element model of the adipose tissues characterized by a constitutive material model that accounted for nonlinear elasticity and time dependence. Mechanical tests have been performed on both SAT and VAT specimens, which have been harvested from patients with severe obesity during standard laparoscopic sleeve gastrectomy intervention. The experimental campaign included indentation tests, which permitted us to obtain the initial/final indentation stiffnesses for each specimen. Statistical results revealed a higher statistical stiffness in SAT than in VAT, with an initial/final indentation stiffness of 1.65 (SD ± 0.29) N/30.30 (SD ± 20) N compared to 1.29 (SD ± 0.30) N/21.00 (SD ± 16) N. Moreover, the results showed that gender, BMI, and age did not significantly affect the stiffness. The experimental results were used in the identification of the constitutive parameters to be inserted in the constitutive material model. Such constitutive characterization of VAT and SAT mechanics can be the starting point for the future development of more accurate computational models of the human adipose tissue and, in general, of the human body for the optimization of numerous medical and biomechanical procedures and applications

Dynamics of circulating microparticles in obesity after weight loss

A definitive relationship between adiposity and MP production is yet to be demonstrated. The aim of our study was to prospectively evaluate the levels of microparticles (MP) in a group of 20 III degree obese patients before and after weight loss. Plasma levels of annexin V-MP, endothelial-derived MP, platelet-derived MP (CD61+ and P-Selectin+), leukocyte-derived MP, tissue factor-bearing (TF+) and CD36+MP were prospectively measured in 20 patients with III degree obesity (BMI ≥ 40 kg/m(2)) before (T0) and 3 (T3) and 12 (T12) months after sleeve gastrectomy (SLG). Obese patients had lost 18 % of their body weight at T3 and 41 % at T12. We find that considering all MP, except for endothelial-derived MP, which had significantly decreased at T3, all MP subtypes had significantly decreased at T12. At T12, subjects showed a higher median level of all types of MP, except endothelial-derived MP, compared to T3, but without a statistically significant difference. The percentages of reduction of all the MP were significantly correlated with the percentage of reduction of BMI. The reductions of leukocyte-derived, TF+ and CD36+MP were significantly correlated with the reduction of leptin. Moreover, the reductions of leukocyte-derived and CD36+MP were significantly correlated with hs-CRP decrease. The decrease of BMI post-SLG in morbid obesity was matched with a decrease of circulating MP of endothelial, platelet, leukocyte origin, TF+ and CD36+. A trend of slight increase in all MP subtypes, except endothelial-derived, was detected 12 months after gastrectomy, indicating a possible underlying slow low-grade inflammatory/hypercoagulability state from adipose tissue before the potential overt weight gain

Laparoscopic Gastric Rebanding for Slippage with Pouch Dilation: Results on 29 Consecutive Patients.

BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) slippage with pouch dilation is one the most serious long-term complications and requires reoperation in most cases. It is still controversial whether banding should be offered again or a different procedure should be chosen. We report the results of synchronous de-rebanding on a prospective series of patients treated at our institution for slippage with pouch dilation. METHODS: From January 2000 to May 2007, 29 consecutive patients underwent laparoscopic de-rebanding for slippage with pouch dilation. The mean age at primary operation was 38.9 +/- 8.2 years and the mean BMI was 46.4 +/- 8 kg/m(2). Twenty-eight had previous LAGB, while one had previous open gastric banding, the perigastric technique being used at that time. All the redo procedures were successfully carried out under laparoscopy, via the pars flaccida technique, and all the patients were followed-up according to the usual schedule. RESULTS: The mean time from the original LAGB was 45.3 +/- 30.3 months, and the mean follow-up after rebanding was 26.9 +/- 20.6 months. At rebanding, the mean BMI was 34.3 +/- 7.6, percent excess weight loss (%EWL) 54.5 +/- 31, and percent excess BMI loss (%EBL) 58.3 +/- 33, respectively. After 1 year, BMI was 36.3 +/- 7.9, %EWL 40.8 +/- 30.5, and %EBL 43.9 +/- 32.7, respectively. After 2 years, BMI was 37.13 +/- 7.4, %EWL 36.9 +/- 29.4, and %EBL 39.6 +/- 31.6, respectively, and after 3 years, BMI was 33.5 +/- 5.6, %EWL 51.9 +/- 24.3, and %EBL 55.7 +/- 25.7, respectively. One patient had re-rebanding after 6 months for a new slippage, two had band removal with refusal to switch to another procedure, one had biliopancreatic diversion for slippage recurrence, and one underwent sleeve gastrectomy for insufficient weight loss after 6 months. CONCLUSIONS: Although this is a limited series, our results show that good outcomes can be expected after rebanding in properly assessed patients with slippage and pouch dilation. Larger series and longer follow-up are needed to confirm these findings