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Insulin-like factor 5 (INSL5), a novel hormone secreted by the enteroendocrine cells of the distal colon, has been implicated in appetite and body weight regulation in animals given its orexigenic properties. We investigated basal INSL5 plasma levels in a group of morbidly obese subjects before and after laparoscopic sleeve gastrectomy. Furthermore, we analyzed the expression of INSL5 in human adipose tissue. Before bariatric surgery, obese subjects showed basal INSL5 plasma levels that were positively correlated with BMI, fat mass, and leptin plasma levels. After weight loss by laparoscopic sleeve gastrectomy, INSL5 plasma levels in obese subjects were significantly lower than those observed before surgery. Finally, we did not detect any expression of the INSL5 gene in human adipose tissue, both at the mRNA and protein levels. The present data show that subjects with obesity have INSL5 plasma levels positively correlating with adiposity markers. After bariatric surgery, INSL5 plasma levels decreased significantly, and this decrease was not directly due to the loss of adipose tissue since this tissue does not express INSL5. Considering the orexigenic properties of INSL5, the reduction of its plasma levels after bariatric surgery in obese subjects could participate in the still unclear mechanisms leading to appetite reduction that characterize bariatric surgery procedures.

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.

Hypoglycemia is a known adverse event following gastric bypass. The incidence of hypoglycemia after laparoscopic sleeve gastrectomy (LSG) is still under investigation. The aim of our study was to verify the presence of oral glucose tolerance test (OGTT)-related hypoglycemia after LSG and to identify any baseline predictors of its occurrence. We analyzed 197 consecutive non-diabetic morbid obese patients that underwent LSG. All patients were studied before and 12 months after LSG. Evaluation included anthropometric parameters, 3-h OGTT for blood glucose (BG), insulin and c-peptide, lipid profile, interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), highly sensitive C-reactive protein (hsCRP), and leptin. Hypoglycemia was defined as BG ≤ 2.7 mmol/l. After surgery, 180 patients completed the OGTT. Eleven patients did not complete the test for gastric intolerance, and in six patients, the test was stopped earlier for the onset of severe symptomatic hypoglycemia. Of the patients, 61/186 (32.8%) had at least one OGTT-related hypoglycemia. The highest frequency of hypoglycemic events occurred 150′ after glucose load (20.2%). At baseline, patients with hypoglycemic events after surgery (Hypo) were younger (40 ± 11 vs 46 ± 10 years; p

Bariatric restrictive procedures induce weight loss by limiting food and calorie intake. This group of procedures is heterogeneous as far as the surgical technique. The consequent anatomical modifications may cause different potential complications. The complications of restrictive procedures need to be properly recognized and addressed, given the high number of patients treated in the past that may require conversion from previous bariatric procedures (vertical banded gastroplasty or gastric banding) or the increasing number of patients subjected to sleeve gastrectomy worldwide. Thorough reassessment via upper gastrointestinal endoscopy and contrast series are the mainstays to approach surgical complications and plan conversion surgery.

Although obesity represents a risk factor for the development of type 2 diabetes mellitus (T2DM), the link between these pathological conditions is not so clear. The manner in which the different elements of adipose tissue (AT) interplay in order to grow has been suggested to have a role in the genesis of metabolic complications, but this has not yet been fully addressed in humans. Through IHC, transmission electron microscopy, cytometry, and in vitro cultures, we described the morphological and functional changes of subcutaneous and visceral AT (SAT and VAT) in normoglycemic, prediabetic and T2DM patients with obesity compared to lean subjects. In both SAT and VAT we measured a hypertrophic and hyperplastic expansion, causing similar vascular rarefaction in obese patients with different degrees of metabolic complications. Capillaries display dysfunctional basement membrane thickening only in T2DM patients evidencing VAT as a new target of T2DM microangiopathy. The largest increase in adipocyte size and decrease in adipose stem cell number and adipogenic potential occur both in T2DM and in prediabetes. We showed that SAT and VAT remodeling with stemness deficit is associated with early glucose metabolism impairment suggesting the benefit of an AT-target therapy controlling hypertrophy and hyperplasia already in prediabetic obese patients.

Fewer studies compared the improvement of plasma lipid levels after different types of surgery, in particular compared to one-anastomosis gastric bypass (OAGB). The aim of our study was to investigate how laparoscopic sleeve gastrectomy (LSG) and OAGB impact on weight loss and lipid profile 18 months after surgery, in patients with severe obesity. Forty-six patients treated with OAGB were matched to eighty-eight patients submitted to LSG. Weight loss after OAGB (33.2%) was more evident than after LSG (29.6%) (p = 0.024). The difference in the prevalence of dyslipidemia showed a statistically significant reduction only after OAGB (61% versus 22%, p &lt, 0.001). After adjustment for delta body mass index (BMI), age and sex, we demonstrated a statistically significant decrease of the differences between the changes before and after (delta Δ) the two surgery procedures: Δ total cholesterol values (p &lt, 0.001), Δ low density lipoprotein-cholesterol values (p &lt, 0.001) and Δ triglycerides values (p = 0.007). Patients with severe obesity undergoing to OAGB presented a better improvement of lipid plasma values than LSG patients. The reduction of lipid plasma levels was independent of the significant decrease of BMI after surgery, of age and of sex.

Obese patients have been described at increased risk of thrombotic thrombocytopenic purpura, a disease caused by anti-ADAMTS13 autoantibodies. ADAMTS13 has a structure homology with the adipokine thrombospondin-1. We previously demonstrated an increased presence of anti-ADAMTS13 antibodies in obese patients. We aimed to study the changes induced by weight loss after bariatric surgery on some inflammatory and coagulative parameters and their link with anti-ADAMTS13 autoantibodies. We studied 100 obese patients before and after weight loss induced by bariatric surgery and 79 lean volunteers as controls. We measured anthropometric, metabolic and inflammatory parameters, thrombospondin-1, ADAMTS13 activity, anti-ADAMTS13 autoantibodies, Von Willebrand factor. At baseline, 13 % of patients was positive for anti-ADAMTS13 autoantibodies, while all controls were negative. Thrombospondin-1 levels were higher in obese subjects with than without antibodies, with a positive correlation between the two parameters. In multiple logistic regression analysis only thrombospondin-1 levels predicted positivity for anti-ADAMTS13 antibodies. After weight loss both anti-ADAMTS13 antibodies and thrombospondin-1 reduced significantly. Weight loss in obesity improves the inflammatory and coagulative profile, and in particular anti-ADAMTS13 autoantibodies, ADAMTS13 activity and thrombospondin-1.

Even though bariatric surgery is one of the most effective treatment option of obesity, post-surgical weight loss is not always ensured, especially in the long term, when many patients experience weight regain. Bariatric procedures are largely based on surgeon's expertise and intra-operative decisions, while an integrated in-silico approach could support surgical activity. The effects of bariatric surgery on gastric distension, which activates the neural circuitry promoting satiety, can be considered one of the main factors in the operation success. This aspect can be investigated trough computational modelling based on the mechanical properties of stomach tissues and structure. Mechanical tests on gastric tissues and structure from people with obesity are carried out, as basis for the development of a computational model. The samples are obtained from stomach residuals explanted during laparoscopic sleeve gastrectomy interventions. Uniaxial tensile and stress relaxation tests are performed in different directions and inflation tests are carried out on the entire stomach residual. Experimental results show anisotropic, non-linear elastic and time-dependent behavior. In addition, the mechanical properties demonstrate to be dependent on the sample location within the stomach. Inflation tests confirm the characteristics of time-dependence and non-linear elasticity of the stomach wall. Experimental activities developed provide a unique set of data about the mechanical behavior of the stomach of patients with obesity, considering both tissues and structure. This data set can be adopted for the development of computational models of the stomach, as support to the rational investigation of biomechanical aspects of bariatric surgery.

Systemic diseases affect multiple tissues that interact with each other within a network difficult to explore at the body level. However, understanding the interdependences between tissues could be of high relevance for drug target identification, especially at the first stages of disease development. In vitro systems have the advantages of accessibility to measurements and precise controllability of culture conditions, but currently have limitations in mimicking human in vivo systemic tissue response. In this work, we present an in vitro model of cross-talk between an ex vivo culture of adipose tissue from an obese donor and a skeletal muscle in vitro model from a healthy donor. This is relevant to understand type 2 diabetes mellitus pathogenesis, as obesity is one of its main risk factors. The human adipose tissue biopsy was maintained as a three-dimensional culture for 48h. Its conditioned culture medium was used to stimulate a human skeletal muscle-on-chip, developed by differentiating primary cells of a patient's biopsy under topological cues and molecular self-regulation. This system has been characterized to demonstrate its ability to mimic important features of the normal skeletal muscle response in vivo. We then found that the conditioned medium from a diseased adipose tissue is able to perturb the normal insulin sensitivity of a healthy skeletal muscle, as reported in the early stages of diabetes onset. In perspective, this work represents an important step toward the development of technological platforms that allow to study and dissect the systemic interaction between unhealthy and healthy tissues in vitro. (c) 2018 American Institute of Chemical Engineers Biotechnol. Prog., 35: e2766, 2019.

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.

Resting energy expenditure (REE) declines more than what is expected according to body composition changes after caloric restriction. This metabolic adaptation is considered one of the factors favoring weight regain. The aim of this study is to evaluate the changes of REE and calculate the degree of metabolic adaptation occurring after laparoscopic sleeve gastrectomy (LSG). REE (by indirect calorimetry) and body composition (fat-free mass or FFM, fat mass or FM by bioelectrical impedance analysis) were determined before and after 12 months in 154 patients with obesity treated with laparoscopic sleeve gastrectomy (LSG). Weight loss was 29.8 ± 10.6%, with corresponding relative reductions in FM (44.5 ± 22.8%), FFM (13.7 ± 9.9%), and REE (27.3 ± 12.9%). A predictive equation for REE was computed by using the baseline FFM and FM values to account for body composition changes. A predicted post-weight loss REE was calculated by using this equation and entering post-weight loss body composition values. Observed post-surgery REE was significantly lower than predicted one (1410 ± 312 vs 1611 ± 340 kcal/day, P

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.

Introduction: Laparoscopic gastric plication (LGCP) reduces gastric volume without resecting or implanting a foreign body. Although still considered investigational, it could be appropriate for young patients with a low body mass index (BMI) and for those unwilling to undergo sleeve gastrectomy, gastric banding, or bypass. Objectives: The aim of this study was to assess the mid-term results (2 years) of LGCP in terms of safety and efficacy. Methods: A total of 56 obese patients (47 female; mean age=30.5±11.7 years; mean BMI=40.31±4.7 kg/m2) were candidates for LGCP from January 2011 to October 2013. Early and late complications, BMI, and excess BMI loss (EBL) were prospectively recorded at 3, 6, 9, 12, 18, and 24 months follow-up. Results: Mean operative time was 72.4±15.6 minutes. No conversion was required. Mean hospital stay was 3 days. Mean %EBL was 34.3±18.40%, 40.1±24.5%, 47.4±30.2%, 46.5±34.6%, 47.8±43.2%, and 55.3±53.6% at 3, 6, 9, 12, 18, and 24 months, respectively. The overall complication rate...

Laparoscopic sleeve gastrectomy (LSG) is considered safe and effective even as conversion procedure after primary bariatric operations. The correlation between gastric pouch volumes and patients weight loss remains unclear. To assess a correlation between the gastric remnant size and the weight loss, we reviewed 49 consecutive barium swallow UGS performed at our institute from August 2012 through May 2014 in LSG patients with symptoms and/or unsatisfactory weight loss. The anteroposterior (AP), laterolateral (LL) and vertical (CC) diameters of the gastric pouch were measured to calculate the volume by the formula of the ellipsoid (AP × LL × CC × 0.5). Patients were divided in two groups: group 1 without gastric pouch (n = 36) and group 2 with gastric pouch (n = 13). Correlation between pouch volume and weight loss data was calculated with t Student’s and Fisher tests to compare the percent excess body mass index (BMI) and percent excess body mass loss (EBL) between two groups, and P

Pre-operative diet may play an important role as far as patients’ fitness for surgery, post-operative outcomes, and successful weight loss. Our aim was to compare surgical outcome and weight loss in two groups of patients who were offered two different pre-operative kinds of diet: very low calorie diet (VLCD) and very low calorie ketogenic diet (VLCKD). Patients candidate for bariatric surgery (laparoscopic sleeve gastrectomy) were registered and assessed according to pre- and post-diet BMI, operative time, hospital stay, drainage output, and hemoglobin (Hb) levels. Patients’ preference influenced the type of diet. From January to December 2016, 178 patients (139 F and 39 M) were enrolled in this study. The mean age was 43 years. In total, 72 patients were on VLCKD while 106 patients on VLCD. Pre-diet mean BMI was 46.3 ± 6.3 kg/m2 for VLCKD group and 43.1 ± 6.9 kg/m2 for VLCD group, while immediately pre-op BMI were 43.9 ± 5.9 kg/m2 and 41.9 ± 6.8 kg/m2, respectively. Drainage output and hemoglobin levels after surgery resulted significantly correlated with diet induced BMI reduction (141.2 ± 75.8 vs. 190.7 ± 183.6 ml, p = 0.032; 13.1 ± 1.2 vs. 12.7 ± 1.5 g/l, p = 0.04). The percentage of patients requiring a hospital stay longer than anticipated (> 3 days) was 2.8% in the VLCKD group and 10.4% in the VLCD group (p = 0.048). In our experience, VLCKD showed better results than VLCD on surgical outcome, influencing drainage output, post-operative hemoglobin levels, and hospital stay.

Laparoscopic greater curvature plication (LGCP) and laparoscopic sleeve gastrectomy (LSG) both reduce gastric capacity, either by in-folding (LGCP) or removing (LSG) the greater curvature. While mid and long-term results of LSG are well known, LGCP is still considered investigational. The aim of this study was to compare the effectiveness of LGCP and LSG in terms of weight loss and safety. Forty-five obese LGCP patients (6 males and 39 females) were matched with 45 LSG patients. The two groups were matched according to sex, age ± 10 years and BMI ± 1 kg/m2. Surgical complication rate, redo surgery need, excess BMI loss (%EBL) and mean BMI at 3 and 6 months were compared. LGCP and LSG mean age was 37.8 and 40 years, while the mean preoperative BMI was 40.65 and 41 kg/m2, respectively. There was no difference in operative time, complication rate, mean BMI and %EBL at 3 months. Redo surgery rate was higher in LGCP group (LGCP 60 % vs LSG 8.8 %, P

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.

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.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.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.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.

Oxygen radicals generated by p66Shc drive adipogenesis, but contradictory data exist on the role of p66Shc in the development of obesity and the metabolic syndrome. We herein explored the relationships among p66Shc, adipose tissue remodelling and glucose metabolism using mouse models and human adipose tissue samples.In wild-type (WT), leptin-deficient (ob/ob), p66Shc(-/-) and p66Shc(-/-) ob/ob mice up to 30 weeks of age, we analysed body weight, subcutaneous and visceral adipose tissue histopathology, glucose tolerance and insulin sensitivity, and liver and muscle fat accumulation. A group of mice on a high fat diet (HFD) was also analysed. A parallel study was conducted on adipose tissue collected from patients undergoing elective surgery.We found that p66Shc(-/-) mice were slightly leaner than WT mice, and p66Shc(-/-) ob/ob mice became less obese than ob/ob mice. Despite their lower body weight, p66Shc(-/-) mice accumulated ectopic fat in the liver and muscles, and were glucose intolerant and insulin resistant. Features of adverse adipose tissue remodelling induced by obesity, including adipocyte enlargement, apoptosis, inflammation and perfusion were modestly and transiently improved by p66Shc (also known as Shc1) deletion. After 12 weeks of the HFD, p66Shc(-/-) mice were leaner than but equally glucose intolerant and insulin resistant compared with WT mice. In 77 patients, we found a direct correlation between BMI and p66Shc protein levels. Patients with low p66Shc levels were less obese, but were not protected from other metabolic syndrome features (diabetes, dyslipidaemia and hypertension).In mice and humans, reduced p66Shc levels protect from obesity, but not from ectopic fat accumulation, glucose intolerance and insulin resistance.

Laparoscopic sleeve gastrectomy (LSG) is now considered an effective bariatric procedure (American Society for Metabolic and Bariatric Surgery statement). We attempted to assess the size of the gastric fundus remaining after LSG and gastric voiding rate (fast/slow) by radiological upper gastrointestinal series (UGS) with a water-soluble contrast medium (CM). The findings were compared with weight loss data. Seventy-four obese patients underwent LSG. Radiological UGS were used to measure the remaining fundus size in 28 of 74 patients 24–72 h after the procedure, with the aid of Matlab software and a library image processing toolbox (MathWorks®). Sleeve voiding was measured in 57 of 74 patients, based on the patients’ radiological reports. The mean volume of the remaining fundus was 17.56 ml (range 1.00–77.03 ml). The mean percent excess BMI loss (%EBL) was 39.5%, 53.7%, and 60.8%, respectively, 3, 6, and 12 months after LSG. Sleeve voiding was fast in 49 of 57 patients (85.96%) and slow in eight (14.03%). No correlation was found between the estimated volume of the remaining gastric fundus and weight loss (%EBL) after LSG. Patients showing a rapid gastroduodenal transit of the CM achieved a better weight loss than patients with a slow voiding rate.

Background Laparoscopic sleeve gastrectomy (LSG) is considered an effective multipurpose operation for morbid obesity, although long-term results are still lacking. Also, the best procedure to be offered in the case of failed restrictive procedures is still debated. We here reported our results of LSG as a revisional procedure for inadequate weight loss and/or complications after adjustable gastric banding or gastroplasty. Methods Since April 2005, 57 patients (20 men and 37 women), with a mean age of 49.9 ± 11.9 years, underwent revisional LSG, 52 after laparoscopic adjustable gastric banding/adjustable gastric banding and 5 after vertical banded gastroplasty at our institution. The mean interval from the primary procedure to LSG was 7.54 ± 4.8 years. The LSG was created using a 34F bougie with an endostapler, after removing the laparoscopic adjustable gastric band or the anterior portion of the band in those who had undergone vertical banded gastroplasty. An upper gastrointestinal contrast study was performed within 3 days after surgery and, if the findings were negative, a soft diet was promptly started. Results A total of 41 patients had undergone concurrent band removal and LSG and 16 had undergone band removal followed by an interval LSG. Three cases required conversion to open surgery because of a large incisional hernia. The mean operative time was 120 minutes (range 90–180). One patient died of multiple organ failure from septic shock. Three patients (5.7%) developed a perigastric hematoma, 3 (5.7%) had leaks, and 1 had mid-gastric short stenosis. The median hospital stay was 5 days. The mean body mass index at revisional LSG was 45.7 ± 10.8 kg/m 2 and had decreased to 39 ± 8.5 kg/m 2 after 2 years, with a mean percentage of the estimated excess body mass index lost of 41.6% ± 24.4%. Two patients required a duodenal switch for insufficient weight loss. Conclusion LSG seems to be effective as revisional procedure for failed LAGB/vertical banded gastroplasty, although with greater complication rates than the primary procedures. Larger series and longer follow-up are needed to confirm these promising results.

Background Liver metastases represent the major determinant of survival in patients with colorectal cancer (CRC). In cases with unresectable liver disease, more effective agents are needed, since chemotherapy achieves median survival of only 15 months. Protein kinases coordinate complex functions that are often disregulated in cancer and are therefore considered important targets for molecular therapeutics. In this study, we investigated the phosphoproteomic status of different protein kinases in primary CRC and in liver metastases. Methods The status of 29 key endpoints was evaluated using reverse phase protein array on laser capture microdissected neoplastic cells from five primary CRCs without metastases, three patient-matched primary CRCs and synchronous liver metastases and five CRC metachronous liver metastases. Results Unsupervised hierarchical two-way clustering analysis showed an entirely different phosphoproteomic profile in primary CRCs compared to liver metastases. This difference was observed also in primary and metastatic patient-matched lesions. Conclusions Our findings of different signaling pathways between primary and metastatic CRC suggest a possible microenvironment effect, and emphasize the need to perform molecular network analysis of metastatic tissue when molecular targeting is considered.