Modifications of IGF2 and EGFR plasma protein concentrations in NAFLD patients after bariatric surgery.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is strictly associated with the epidemic of obesity and is becoming the most prevalent liver disease worldwide. In severe obesity, bariatric surgery (BS) is the most effective treatment not only for obesity but also for the associated metabolic co-morbidities, NAFLD, among others. To date, noninvasive diagnostic/prognostic methods cannot evaluate hepatic improvements following surgery. OBJECTIVES: We aimed to measure plasma level of insulin-growth factor-2 protein (IGF2) and epithermal growth factor receptor (EGFR), and to assess their relationship with clinical and biochemical parameters during the 12 months follow-up. METHODS: Demographic, clinical-biochemical data, and plasma IGF2 and EGFR were measured in 69 patients preoperatively (T0) and 6 and 12 months (T6M and T12M, respectively) after BS. Liver biopsy was performed at T0. Relationships between IGF2, EGFR, and several biochemical parameters were performed using Pearson or Spearman correlation analysis. RESULTS: IGF2 plasma level increases during follow-up, passing from 2.5 (1.8-15.5) at baseline to 13.3 (8.6-19.1) at T12M, p < 0.001. Conversely, EGFR showed a not significant reduction. At T12M, the plasma level of both markers was comparable to those of lean subjects. The clinical-biochemical parameters (BMI, glycated hemoglobin, HOMA-IR) also return to the normal range at T12M. Correlation analysis demonstrated that IGF2 was significantly associated with total bilirubin, direct bilirubin, and albumin at T0 while with blood glucose, ALT, GGT, and AST/ALT ratio at T6M and T12M. CONCLUSIONS: IGF2 plasma levels increase after bariatric surgery, and these changes are associated with the modification of hepatic biochemical parameters, even if other clinic or metabolic improvements cannot be excluded.

Optimization of Point-Shear Wave Elastography by Skin-to-Liver Distance to Assess Liver Fibrosis in Patients Undergoing Bariatric Surgery.

BACKGROUND: Obesity is a primary limiting factor in liver stiffness measurement (LSM). The impact of obesity has always been evaluated in terms of body mass index (BMI), without studying the effects of skin-to-liver distance (SLD) on LSM. We studied the impact of SLD on LSM in a cohort of obese patients undergoing bariatric surgery and intra-operatory liver biopsy. MATERIALS AND METHODS: 299 patients underwent LSM by point-shear wave elastography (ElastPQ protocol), with two different ultrasound machines. SLD was measured as the distance between the skin and the liver capsule, perpendicular to where the region of interest (ROI) was positioned. We used the following arbitrary cut-offs: <5.7 kPa, F0-1; 5.7-7.99 kPa, F2; ≥8 kPa, F3-4. RESULTS: We developed two logistic regression models using elastography-histology agreement (EHA) as the dependent variable and SLD as the independent variable. The model based on the second machine showed strongly more performant discriminative and calibration metrics (AIC 38.5, BIC 44.2, Nagelkerke Pseudo-R2 0.894, AUROC 0.90). The SLD cut-off value of 34.5 mm allowed a correct EHA with a sensitivity of 100%, a specificity of 93%, negative predictive value of 100%, positive predictive value of 87%, an accuracy of 96%, and positive likelihood ratio of 3.56. CONCLUSION: The impact of SLD is machine-dependent and should be taken into consideration when interpreting LSM. We believe that our findings may serve as a reference point for appropriate fibrosis stratification by liver elastography in obese patients.

Differentiation between stages of non-alcoholic fatty liver diseases using surface-enhanced Raman spectroscopy.

Non-alcoholic fatty liver disease (NAFLD) is a chronic disorder progressing from an initial benign accumulation of fat (NAFL) towards steatohepatitis (NASH), a degenerative form that can lead to liver cirrhosis and cancer. The development of non-invasive, rapid and accurate method to diagnose NASH is of high clinical relevance. Surface-enhanced Raman spectroscopy (SERS) of plasma was tested as a method to distinguish NAFL from NASH. SERS spectra from plasma of female patients diagnosed with NAFL (n = 32) and NASH (n = 35) were obtained in few seconds, using a portable Raman spectrometer. The sample consisted of 5 µL of biofluid deposited on paper coated with Ag nanoparticles. The spectra show consistent differences between the NAFL and NASH patients, with the uric acid/hypoxanthine band area ratio statistically different (p-value <0.001) between the two groups. The average figures of merit for a diagnostic test based on these ratios, as derived from a repeated 4-fold cross-validation of a logistic regression model, are all between 0.73 and 0.79, with an average area under the curve of 0.81. We conclude that SERS may be a reliable and rapid method to discriminate NAFLD from NASH.

Changes in Gut Microbiota Composition after Bariatric Surgery: a New Balance to Decode.

BACKGROUND: Recently, the link between obesity and gut microbiota has become a focus for research. This study shed some light on the modification of postoperative gut microbial composition after bariatric surgery. METHODS: A prospective longitudinal study on healthy lean subjects and patients who underwent bariatric surgery (Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy) was carried out. Anthropometric and metabolic data, smoking, food preferences data, and stool samples were collected from lean subjects and from obese patients before and 3 and 6 months after surgery (T0, T3, and T6, respectively). RESULTS: We collected stool samples from 25 obese patients before surgery and 3 and 6 months thereafter and from 25 normal weight patients. After Roux-en-Y gastric bypass, Yokenella regensburgei (p < 0.05), Fusobacterium varium (p < 0.05), Veillonella dispar/atypica (p < 0.05), and Streptococcus australis/gordonii (p < 0.05) were transiently identified in the gut at T3. Roux-en-Y gastric bypass patients had a permanent increase in Akkermansia muciniphila (p < 0.05), which is associated with healthy metabolism, both at T3 and T6. There were no significant changes in gut microbiota in laparoscopic sleeve gastrectomy patients. CONCLUSIONS: In our study, Roux-en-Y gastric bypass induced major microbial differences and greater weight loss compared with laparoscopic sleeve gastrectomy. Analyzing the microbiota composition, a proliferation of potential pathogens and the onset of beneficial bacteria was observed. The effects of these bacteria on human health are still far from clear. Understanding the mechanisms of action of these bacteria could be the keystone in developing new therapeutic strategies for obesity.

Bariatric surgery drives major rearrangements of the intestinal microbiota including the biofilm composition.

The intestinal microbiota disequilibrium has been associated with obesity, while the role of the gut mucosal biofilms in this pathology is still unknown. We analysed the changes in the intestinal microbiota of obese patients after bariatric surgery with the aim of disclosing the rearrangement of the biofilm configuration. Although the bariatric surgery drives major rearrangements of the gut microbiota, obese patients maintain the Prevotella enterotype before and after surgery, as shown by normal weight patients, with an increase of Bacteroides vulgatus and Bacteroides uniformis. The Bacteroides enterotype guarantees the strong ability to form a biofilm which allows a more efficient digestion of polysaccharides than planktonic communities and leads to the production of acetate which is a key player to inhibit enteropathogens. Additionally, the laparoscopic gastric bypass induces an increase of Hafniaalvei (Proteobacteria), a facultative anaerobic bacterium involved in intestinal and inflammatory disorders. Bariatric surgery influences the microbial composition of gut biofilm. Further studies are needed to elucidate the impact of this variation on recovery after surgery and on weight loss.

A simple in silico strategy identifies candidate biomarkers for the diagnosis of liver fibrosis in morbidly obese subjects.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disorder, tightly associated with obesity. The histological spectrum of the disease ranges from simple steatosis to steatohepatitis, with different stages of fibrosis, and fibrosis stage is the most significant predictor of mortality in NAFLD. Liver biopsy continues to be the gold standard for its diagnosis and reliable non-invasive diagnostic tools are unavailable. We investigated the accuracy of candidate proteins, identified by an in silico approach, as biomarkers for diagnosis of fibrosis. METHODS: Seventy-one morbidly obese (MO) subjects with biopsy-proven NAFLD were enrolled, and the cohort was subdivided according to minimal (F0/F1) or moderate (F2/F3) fibrosis. The plasmatic level of CD44 antigen (CD44), secreted protein acidic and rich in cysteine (SPARC), epidermal growth factor receptor (EGFR) and insulin-like growth factor 2 (IGF2) were determined by ELISA. Significant associations between plasmatic levels and histological fibrosis were determined by correlation analysis and the diagnostic accuracy by the area under receiver operating characteristic curves (AUROC). RESULTS: Eighty-two percentage of the subjects had F0/F1 and 18% with F2/F3 fibrosis. Plasmatic levels of IGF2, EGFR and their ratio (EGFR/IGF2) were associated with liver fibrosis, correlating inversely for IGF2 (P < .006) and directly (P < .018; P < .0001) for EGFR and EGFR/IGF2 respectively. The IGF2 marker had the best diagnostic accuracy for moderate fibrosis (AUROC 0.83), followed by EGFR/IGF2 ratio (AUROC 0.79) and EGFR (AUROC 0.71). CONCLUSIONS: Our study supports the potential utility of IGF2 and EGFR as non-invasive diagnostic biomarkers for liver fibrosis in morbidly obese subjects.

Outcome of laparoscopic gastric bypass in obese and diabetic patients: when surgery fails.

BACKGROUND: The beneficial effects of bariatric surgery on diabetes and obesity have been widely demonstrated in the literature. The aim of our study was to evaluate the rate of failure of laparoscopic gastric bypass both in terms of weight loss and metabolic remission after one follow-up year. METHODS: A longitudinal, multicenter prospective study was carried out on 771 patients affected by pathological obesity. The following parameters were recorded for each patient before surgery: anthropometric, metabolic, social, smoking habits and previous failure of other bariatric procedures. After 1 follow-up year, final weight, final Body Mass Index (BMI), final percentage of lost excess body weight and percentage of lost BMI were evaluated. RESULTS: Statistical analysis showed a correlation between BMI>50 kg/m2, presence of metabolic syndrome, presence of diabetes, gastric pouch volume greater than 60 mL and failure of weight loss outcome. Statistical analysis of metabolic failure has recognized a high preoperative glycated hemoglobin percentage (HbA1c%) value as a statistically significant negative predictive factor. CONCLUSIONS: Bariatric Surgery is the most effective treatment for weight loss and metabolic improvement. However, in our study, surgery did not achieve the expected outcome in patients with specific metabolic, anthropometric and surgical characteristics (BMI>50 kg/m2, presence of metabolic syndrome, presence of T2DM with high preoperative HbA1c% level and gastric pouch volume greater than 60 mL).

Intragastric Balloon Device: Weight Loss and Satisfaction Degree.

BACKGROUND: An intragastric balloon is a non-surgical device enhancing a sensation of early satiety and reducing food intake. The aim of this study is to analyze the results in terms of weight loss and patient satisfaction undergoing intragastric balloon implantation. METHODS: Air-filled and water-filled devices were used. All patients were participated in strict follow-up programs. Weight, body mass index (BMI), total body weight loss (TWL), percentage of excess weight loss (EWL), and satisfaction degree were taken into account. RESULTS: Eighty-one patients completed a 6-month period with a device in place; 72 of them were then contacted for a follow-up at 12.3 ± 2.4 months post-removal. During treatment period, in 76 cases (93.8 %), a statistically significant reduction in weight was observed. A statistically meaningful linear correlation between a 3-month EWL (or TWL) and a 6-month EWL (or TWL) was found. At the end of endoscopic treatment, a significant link between baseline BMI and EWL >20 % was found. Sixty-three percent of the patients were not satisfied with the procedure, did not deem useful to change their diet, and refused to perform it again. CONCLUSIONS: In our study, at device removal and 1 year thereafter, a statistically significant reduction in weight was observed. Most of the patients were found to have a weight loss more than the cut-off of 20 %. The weight reached at the third month appears to be predictive of the effectiveness of endoscopic treatment. Data showed an overall dissatisfaction with procedure.

Gastric bypass-induced weight loss alters obesity-associated patterns of plasma pentraxin-3 and systemic inflammatory markers.

BACKGROUND: Systemic inflammation contributes to obesity-associated complications. The short pentraxin C-reactive protein (CRP) is a validated inflammatory marker, whereas long pentraxin-3 (PTX3) limits inflammation and is adaptively stimulated by proinflammatory cytokines in vitro. Severely obese (SO) patients (body mass index [BMI]>40] have the highest obesity-associated complications and increasingly undergo surgical treatment. SO-associated changes in plasma PTX3 and their interactions with systemic inflammation are, however, unknown. OBJECTIVE: We sought to determine potential alterations in plasma PTX3 and their associations with changes in inflammatory markers before and after weight loss induced by laparoscopic Roux-en-Y gastric bypass (LRYGB). SETTING: University hospital in Trieste, Italy. METHODS: Plasma PTX3, CRP, and cytokines, including tumor necrosis factor α and interleukin 6 were measured in (1) 24 individuals with severe, class III obesity (SO; age = 42 ± 1 yr, female/male = 18/6, BMI = 45 ± 1 kg/m(2)) before and 3, 6, and 12 months after LRYGB; and (2) age- and sex-matched normal-weight (N; n = 56, BMI = 22 ± .2 kg/m(2)) or class I obese individuals (O; n = 44, BMI = 31.2 ± .3 kg/m(2)). RESULTS: SO, but not O, had higher plasma PTX3 compared with N, associated with highest proinflammatory cytokines and CRP (P<.05 versus N-O). In all patients, plasma interleukin 6 and tumor necrosis factor α were associated positively with PTX3 (P<.05). Plasma CRP and proinflammatory cytokines declined during LRYGB-induced weight loss. In contrast, high PTX3 further increased and remained elevated (P<.05 versus basal). CONCLUSIONS: Obesity level and energy balance modulate interactions between PTX3 and systemic inflammation. Elevated PTX3 is a novel, potentially adaptive alteration associated with proinflammatory cytokines in SO. Their differential changes conversely suggest circulating PTX3 as a novel negative inflammatory marker in SO undergoing LRYGB-induced weight loss.

Preoperative Predictive Factors of Successful Weight Loss and Glycaemic Control 1 Year After Gastric Bypass for Morbid Obesity.

BACKGROUND: Gastric bypass (GBP) is one of the most effective surgical procedures to treat morbid obesity and the related comorbidities. This study aimed at identifying preoperative predictors of successful weight loss and type 2 diabetes mellitus (T2DM) remission 1 year after GBP. METHODS: Prospective longitudinal study of 771 patients who underwent GBP was performed at four Italian centres between November 2011 and May 2013 with 1-year follow-up. Preoperative anthropometric, metabolic and social parameters, the surgical technique and the previous failed bariatric procedures were analyzed. Weight, the body mass index (BMI), the percentage of excess weight lost (% EWL), the percentage of excess BMI lost (% BMIL) and glycated haemoglobin (HbA1c) were recorded at follow-up. RESULTS: Univariate and multivariate analysis showed that BMI <50 kg/m(2) (p = 0.006) and dyslipidaemia (p = 0.05) were predictive factors of successful weight loss. Multivariate analysis of surgical technique showed significant weight loss in patients with a small gastric pouch (p < 0.001); the lengths of alimentary and biliary loops showed no statistical significance. All diabetic patients had a significant reduction of HbA1c (p < 0.001) after surgery. BMI ≥ 50 kg/m(2) (p = 0.02) and low level of preoperative HbA1c (p < 0.01) were independent risk factors of T2DM remission after surgery. CONCLUSIONS: This study provides a useful tool for making more accurate predictions of best results in terms of weight loss and metabolic improvement.

Totally hand-sewn anastomosis using barbed suture device during laparoscopic gastric bypass in obese. A feasibility study and preliminary results.

INTRODUCTION: Barbed sutures are routinely used for laparotomy, peritoneal and mesenteric closure, but few studies have reported their use for intestinal anastomosis. We proposed their use for totally hand-sewn anastomosis during laparoscopic gastric bypass secured at the end of the suture with an absorbable clip. MATERIALS AND METHOD: Two totally hand-sewn single-layer extramucosal running sutures were performed for side-to-side gastrojejunal and jejuno-jejunal anastomosis during laparoscopic gastric bypass. Each run (anterior and posterior layer) was locked at the end by an absorbable poly-p-dioxanone suture clip. RESULTS: A total of 96 hand-sewn anastomoses were performed. A total of two leaks occurred originating from the jejunaljejunal anastomosis. No cases of leakage from gastrojejunostomy were recorded. Two stenoses of the gastrojejunal anastomosis were recorded. They were successfully treated with three sessions of endoscopic balloon dilatation. No bleeding occurred. CONCLUSION: In our experience, the suture-related complication rate is comparable with the data reported in the literature. Further studies are needed to address the safety and efficacy of the self-maintained suture in digestive surgery.

Zero frequency of internal hernias after laparoscopic double loop gastric bypass without closure of mesenteric defects.

PURPOSE: Laparoscopic Roux-en-Y gastric bypass is among the most effective surgical procedures for morbid obesity; however, one of its most common long-term complications is internal hernia. The purpose of this study was to evaluate the incidence of internal hernia in patients undergoing a new gastric bypass surgical technique known as "double loop" without closure of the mesenteric defects. METHODS: We reviewed 44 patients with morbid obesity, who underwent laparoscopic double loop gastric bypass. There were 34 women and 10 men, followed up for a mean period of 18 ± 3 months, mainly by periodic medical examinations and blood tests. RESULTS: The initial body mass index (BMI) was 44.23 ± 4.7 and the mean % excess weight (%EW) was 105.83 ± 24.41. After 18 postoperative months, the mean BMI was 29.68 ± 3.7 kg/m(2), representing a mean loss of 14.5 BMI units, with the mean % excess weight loss (%EWL) of 64.33 ± 13.47. No cases of internal hernia were recorded. CONCLUSIONS: Laparoscopic double loop gastric bypass without closure of the mesenteric defects is a safe and feasible procedure. A longer observational follow-up and a large number of patients are required to confirm significant results.

Safety of Veress needle insertion in laparoscopic bariatric surgery.

BACKGROUND: Creating the pneumoperitoneum is the first surgical procedure in laparoscopic abdominal surgery. Morbid obesity is a risk factor for iatrogenic injuries because of the considerable thickness of the abdominal wall. The aim of this study was to assess the feasibility and the incidence of complications when using Veress needles (VN) in obese patients undergoing bariatric surgery. METHODS: Between March 2004 and December 2010, a retrospective analysis was performed on 139 obese patients (mean body mass index=45.94 kg/m). Blind VN insertion followed by optical trocar insertion was the most widely used technique. RESULTS: Of the 139 patients, VN was successfully used in 138 cases (99.28%), and in 1 patient the procedure failed and an open laparoscopy was performed (0.72%). During the study period, there were 63 gastric bypasses, 18 sleeve gastrectomies, 50 gastric bandings, and 8 reoperations. The VN was inserted in the left upper quadrant in 46 cases and in the midline above the umbilicus in 93 cases. A colonic perforation after VN insertion at the left upper quadrant occurred. The overall rate of complications was 0.72%. There were no access-related complications when VN was inserted above the umbilicus; complication rate was 2.17% at upper left quadrant VN placement. No cases of subcutaneous emphysema or extraperitoneal insufflation were observed. CONCLUSIONS: In our experience, the success rate was 98.28% and the overall rate of complications was 0.72%. The VN technique can be considered feasible and safe even when used in obese population.

Gastric bypass does not normalize obesity-related changes in ghrelin profile and leads to higher acylated ghrelin fraction.

OBJECTIVE: Gastric bypass (GBP) lowers food intake, body weight, and insulin resistance in severe obesity (SO). Ghrelin is a gastric orexigenic and adipogenic hormone contributing to modulate energy balance and insulin action. Total plasma ghrelin (T-Ghr) level is low and inversely related to body weight and insulin resistance in moderately obese patients, but these observations may not extend to the orexigenic acylated form (A-Ghr) whose plasma concentration increase in moderate obesity. DESIGN AND METHODS: We investigated the impact of GBP on plasma T-, A-, and A/T-Ghr in SO patients (n = 28, 20 women), with measurements at baseline and 1, 3, 6, and 12 months after surgery. Additional cross-sectional comparison was performed between nonobese, moderately obese, and SO individuals before GBP and at the end of the follow-up period. RESULTS: Before GBP, SO had lowest T-Ghr and highest A/T-Ghr profile compared with both nonobese and moderately obese individuals. Lack of early (0-3 months from GBP) T-Ghr changes masked a sharp increase in A-Ghr and A/T-Ghr profile (P < 0.05) that remained elevated following later increments (6-12 months) of both T- and A-Ghr (P < 0.05). Levels of A-Ghr and A/T-Ghr at 12 months of follow-up remained higher than in matched moderately obese individuals not treated with surgery (P < 0.05). CONCLUSIONS: The data show that following GBP, early T-Ghr stability masks elevation of A/T-Ghr, that is stabilized after later increments of both T- and A-hormones. GBP does not normalize the obesity-associated elevated A/T-Ghr ratio, instead resulting in enhanced A-Ghr excess. Excess A-Ghr is unlikely to contribute to, and might limit, the common GBP-induced declines of appetite, body weight, and insulin resistance.

Bowel obstruction after cardiac surgery due to diaphragmatic unrecognised hernia.

Diaphragmatic hernia is a very rare occurrence after cardiac surgery without complications. We report a case of a 66-year-old male who underwent double aortocoronary bypass surgery, mitral and tricuspidal annuloplasty developed bowel obstruction 5 months after the operation. X-ray demonstrated small bowel loops in the left side of the chest. A laparoscopy was performed, but during the reduction of the hernia, patient suffered bradycardia because of adhesions between bowel and pericardical sac. Operation was interrupted and patient was transferred to our hospital where a cardiac surgery unit is present. No hemodynamic or respiratory deterioration was observed. Thoracic abdominal entero-CT, transthoracical echocardiography were performed. Patient underwent second surgery in cooperation with the cardial surgical team. Sternotomy was carried out. Hernial content was drawn onto the abdomen, diaphragmatic defect was closed with a direct suture. Mini-laparotomy was performed to exclude that the herniated small bowel did not have ischaemic suffering. No morbidity was observed in the post-operative course. This case illustrates the importance of an accurate pre-operative diagnosis in order to obtain information on relationship between loops of bowel and mediastinal organs. If sternotomy is required, surgical team must be supported by a cardiac surgical team.