Transcriptional and epigenetic changes after dietary and surgical weight loss interventions in an animal model of obesity.

BACKGROUND: Identifying determinants that can predict response to weight loss interventions is imperative for optimizing therapeutic benefit. We aimed to identify changes in DNA methylation and mRNA expression of a subset of target genes following dietary and surgical interventions in high-fat-diet (HFD)-induced obese rats. METHODS: Forty-two adult Wistar Han male rats were divided into two groups: control rats (n = 7) and obese rats (n = 28), fed a HFD for 10 weeks (t10). Obese rats were randomly subdivided into five intervention groups (seven animals per group): (i) HFD; (ii) very-low-calorie diet (VLCD); (iii) sham surgery, and (iv) sleeve gastrectomy (SG). At week sixteen (t16), animals were sacrificed and tissue samples were collected to analyze changes in DNA methylation and mRNA expression of the selected genes. RESULTS: By type of intervention, the surgical procedures led to the greatest weight loss. Changes in methylation and/or expression of candidate genes occurred proportionally to the effectiveness of the weight loss interventions. Leptin expression, increased sixfold in the visceral fat of the obese rats, was partially normalized after all interventions. The expression of fatty acid synthase (FASN) and monocyte chemoattractant protein 1 (MCP-1) genes, which was reduced 0.5- and 0.15-fold, respectively, in the liver tissue of obese rats, were completely normalized after weight loss interventions, particularly after surgical interventions. The upregulation of FASN and MCP-1 gene expression was accompanied by a significant reduction in promoter methylation, up to 0.5-fold decrease in the case of the FASN (all intervention groups) and a 0.8-fold decrease in the case of the MCP-1 (SG group). CONCLUSIONS: Changes in tissue expression of specific genes involved in the pathophysiological mechanisms of obesity can be significantly attenuated following weight loss interventions, particularly surgery. Some of these genes are regulated by epigenetic mechanisms.

Morbidity and mortality of elderly patients with pancreaticobiliary disease according to age and comprehensive geriatric assessment: A prospective observational study.

BACKGROUND: This study was designed to analyze the influence of age and comprehensive geriatric evaluation on clinical results of pancreaticobiliary disease management in elderly patients. METHODS: A prospective observational study has been undertaken, including 140 elderly patients (over 75 years) with benign pancreaticobiliary disease. Patients were divided according to age in the following groups: group 1: 75-79 years old; group 2: 80-84 years old; group 3: 85 years and older. They underwent a comprehensive geriatric assessment with different scales: Barthel Index, Pfeiffer Index, Charlson Index, and Fragility scale, at admission and had been follow-up 90 days after hospital discharge to analyze its influence on morbidity and mortality. RESULTS: Overall, 140 patients have been included (group 1=51; group 2=43 and group 3=46). Most of them, 52 cases (37.8%), had acute cholecystitis, followed by 29 cases of acute cholangitis (20.2%) and acute pancreatitis with 25 cases (17.9%). Significant differences has been observed on complications in different age groups (p=0.033). Especially in patients with a Barthel Index result ≤60, which suggests that these less functional patients had more severe complications after their treatment (p=0.037). The mortality rate was 7.1% (10 patients). CONCLUSIONS: No significant differences were found between age, morbidity and mortality in elderly patients with pancreaticobiliary disease. Comprehensive geriatric scales showed some utility in their association with specific complications.

Fluorescent cholangiography with direct injection of indocyanine green (ICG) into the gallbladder: a safety method to outline biliary anatomy.

PURPOSE: Near infrared cholangiography (NIRC) with indocyanine green (ICG) directly injected into the gallbladder is a novel technique to outline biliary anatomy. The purpose of this article is to analyze the usefulness and feasibility of NIRC as a safety method during laparoscopic cholecystectomies. MATERIAL AND METHODS: A case-controlled study comparing 20 patients undergoing laparoscopic cholecystectomies with NIRC with direct injection of ICG into the gallbladder to 20 consecutive standard cholecystectomies. Operative time, length of stay, complications, conversion rates, and biliary injury were analyzed. RESULTS: Both groups were comparable in epidemiological characteristics. In the ICG group fluorescent visualization of the junction of the Hartmann pouch and the whole cystic duct was achieved in 16 (80%) patients. Median surgical time was 65 (50-76) and 55 (45-71) min for the ICG and the control group, respectively (p = 0.113). There were no postoperative complications and no biliary duct injuries in any of the groups, and a patient from both groups underwent conversion to open surgery. CONCLUSION: NIRC with direct injection of ICG into the gallbladder is a feasible method that is not time-consuming; it does not require a different learning curve from standard laparoscopic cholecystectomies and has no major complications described so far.

Secondary node analysis as an indicator for axillary lymphadenectomy in breast cancer patients. / Ganglio secundario como indicador de linfadenectomía axilar en pacientes afectas de cáncer de mama.

INTRODUCTION: Currently, there is no agreement regarding if it would be necessary to perform an axillary lymph node dissection (ALND) in patients who have macrometastases in the sentinel lymph node (SLN). We studied the utility of the secondary node analysis (SN), defined as the following node after the SLN in an anatomical and lymphatic pathway, as a sign of malignant axillary involvement. METHODS: An observational, retrospective and multicentre study was designed to assess the utility of the SN as a sign of axillary involvement. Among 2273 patients with breast cancer, a valid sample of 283 was obtained representing those who had the SN studied. Main endpoints of our study were: the SLN, the SN and the ALND histological pattern. Sensitivity, specificity and precision of the test were also calculated. RESULTS: SN test, in cases with positive SLN, has a sensitivity of 61.1%, a specificity of 78.7%, a positive predictive value of 45.8% and a negative predictive value of 87.3% with a precision of 74.7%. CONCLUSION: The study of the SN together with the technique of the SLN allows a more precise staging of the axillary involvement, in patients with breast cancer, than just the SLN technique.

Economic impact of outpatient follow-up using telemedicine vs in-person visits for patients in general surgery: A secondary analysis of a randomized clinical trial.

INTRODUCTION: Innovation in internet connectivity and the Covid 19 pandemic have caused a dramatic change in the management of patients in the medical field, boosting the use of telemedicine. A comparison of clinical outcomes and satisfaction between conventional face-to-face and telemedicine follow-up in general surgery, an economic evaluation is mandatory. The aim of the present study was to compare the differences in economic costs between these two outpatient approaches in a designed randomized controlled trial (RCT). METHODS: A RCT was conducted enrolling 200 patients to compare conventional in-person vs. digital health follow-up using telemedicine in the outpatient clinics in patients of General Surgery Department after their planned discharge. After a demonstration that no differences were found in clinical outcomes and patient satisfaction, we analyzed the medical costs, including staff wages, initial investment, patent's transportation and impact on social costs. RESULTS: After an initial investment of 7527.53€, the costs for the Medical institution of in-person conventional follow-up were higher (8180.4€) than those using telemedicine (4630.06€). In relation to social costs, loss of productivity was also increased in the conventional follow-up. CONCLUSION: The use of digital Health telemedicine is a cost-effective approach compared to conventional face-to-face follow-up in patients of General Surgery after hospital discharge.

Clinical results after external reinforcement of colorectal anastomosis: a systematic review.

OBJECTIVE: The aim of this review is to describe and assess the existing methods to cover colorectal anastomoses with biomaterials and their clinical impact in reducing anastomotic leakage (AL). SUMMARY BACKGROUND DATA: The most serious complication in colorectal surgery is AL. Despite improvements in its diagnosis and management, AL remains an unresolved issue. To prevent its appearance and clinical consequences, different external reinforcement techniques with synthetic or biomaterials have been described. METHODS: A systematic review search of the available literature until June 2022 was performed, looking for all literature regarding external reinforcement of colonic or colorectal anastomoses. After the review process, a classification of materials was proposed into solid and liquid materials, and an assessment of their clinical impact was performed. The study protocol has been registered at PROSPERO and has been reported in the line with PRISMA and AMSTAR Guidelines 11,12 . RESULTS: Ninety-seven articles that fulfilled inclusion criteria, were identified and revised. Overall, 18 of the selected articles focused on human clinical trials and 79 on animal models. Only fibrin sealants, collagen patches, and omentoplasty have shown positive results in humans. CONCLUSIONS: Fibrin sealants, collagen patches, and omentoplasty are, so far, the most studied biomaterials. However, further studies are required to confirm these findings before definite recommendations can be made.

Telemedicine to follow patients in a general surgery department. A randomized controlled trial.

BACKGROUND: Telemedicine is becoming more popular in many medical specialties but few studies have been conducted in General Surgery. This study aims to evaluate the feasibility of its introduction in this specialty. METHODS: A prospective randomized clinical trial (RCT) was conducted in 200 patients to compare conventional vs telemedicine follow-up in the outpatient clinics. The primary outcome was the feasibility of telemedicine follow-up and the secondary outcomes were its clinical impact and patient satisfaction. RESULTS: Patients were enrolled between March 2017 and April 2018 and there were no statistically significant differences between the groups' characteristics. The primary outcome was achieved in 90% of the conventional follow-up group and in 74% of the telemedicine group (P = 0.003). No differences were found in clinical outcomes (P = 0.832) or patient satisfaction (P = 0.099). CONCLUSION: Telemedicine is a good complementary service to facilitate follow-up management in selected patients from a General Surgery department.

Laparoscopic sleeve gastrectomy induces molecular changes in peripheral white blood cells.

BACKGROUND & AIMS: Peripheral white blood cells (PWBC) may allow for the development of obesity biomarkers. We aimed to investigate the existence of gene expression and DNA methylation changes in PWBC after a very low calorie diet (VLCD) followed by a laparoscopic sleeve gastrectomy (LSG), and its correlation with surgical outcomes. METHODS: From July 2013 to June 2014, 35 consecutive bariatric patients and 33 healthy lean volunteers were recruited. Molecular data was obtained once on the control group and at 3 different times on the LSG group: 1) at baseline; 2) after 2 weeks of VLCD, right before LSG; and 3) 6 months after LSG. The expression of 12 genes in PWBC was analyzed by quantitative real-time polymerase chain reaction: ghrelin (GHRL), visfatin (NAMPT), insulin receptor substrate 1 (IRS1), fat mass and obesity-related gene (FTO), leptin (LEP), peroxisome proliferator-activated receptor gamma (PPARG), adiponectin (ADIPOQ), fatty acid synthase (FASN), melanocortin 4 receptor (MC4R), fas cell surface death receptor (FAS), tumor necrosis factor alpha (TNF) and chemokine (C-C motif) ligand 2 (CCL2). Moreover, DNA methylation of GHRL, NAMPT and FAS promoters was analyzed in PWBC by bisulfite pyrosequencing. RESULTS: Seven genes (GHRL, NAMPT, IRS1, FTO, FAS, TNF and CCL2) had detectable expression in PWBC. FTO expression at baseline was lower in patients than in controls (p = 0.042), equalizing after LSG. In patients, FAS expression decreased after VLCD (p = 0.01) and stayed low after LSG (p = 0.015). Also, CCL2 expression decreased 50% after LSG compared to pre-surgical levels (p = 0.016). All studied CpG sites in the GHRL gene promoter followed a consistent pattern of DNA methylation/demethylation. No direct correlation between these molecular changes and surgical outcomes was found at 1-year follow-up. CONCLUSIONS: FTO expression increased and FAS and CCL2 expression decreased in PWBC after LSG. Molecular changes did not correlate with surgical outcomes.

Morphofunctional Changes After Sleeve Gastrectomy and Very Low Calorie Diet in an Animal Model of Non-Alcoholic Fatty Liver Disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease and is found in 70% of obese people. The evidence available to date suggests that bariatric surgery could be an effective treatment by reducing weight and also by improving metabolic complications in the long term. This work aimed to compare, in a diet-induced NAFLD animal model, the effect of both sleeve gastrectomy (SG) and very-low calorie diet (VLCD). METHODS: Thirty-five Wistar rats were divided into control rats (n = 7) and obese rats fed a high-fat diet (HFD). After 10 weeks, the obese rats were subdivided into four groups: HFD (n = 7), VLCD (n = 7), and rats submitted to either a sham operation (n = 7) or SG (n = 7). Both liver tissue and blood samples were processed to evaluate steatosis and NASH changes in histology (Oil Red, Sirius Red and H&E); presence of endothelial damage (CD31, Moesin/p-Moesin, Akt/p-Akt, eNOS/p-eNOS), oxidative stress (iNOS) and fibrosis (αSMA, Col1, PDGF, VEGF) proteins in liver tissue; and inflammatory (IL6, IL10, MCP-1, IL17α, TNFα), liver biochemical function, and hormonal (leptin, ghrelin, visfatin and insulin) alterations in plasma. RESULTS: Both VLCD and SG improved histology, but only SG induced a significant weight loss, improved endothelial damage, and a decreased cardiovascular risk by reducing insulin resistance (IR), leptin, total cholesterol, and triglyceride levels. There were no relevant variations in the inflammatory and fibrosis markers. CONCLUSION: Our study suggests a slight superiority of SG over VLCD by improving not only the histology but also the IR and cardiovascular risk markers related to NAFLD.