[Bariatric endoscopy-Possibilities and value in obesity medicine and surgery-A separate special field]. / Bariatrische Endoskopie ­ Möglichkeiten und Stellenwert in der Adipositasmedizin und -chirurgie ­ ein eigenes Spezialgebiet.

Endoscopy has become established as an important component in all preoperative, intraoperative and postoperative areas of bariatric surgery. As guidelines are not yet available, relevant studies and international position papers have been collected in this article. Preoperatively, endoscopy should be performed before sleeve gastrectomy (SG, detection of reflux status) and before bypass procedures (status survey of the postoperatively no longer accessible distal stomach). Routine endoscopic monitoring should be performed 2-3 years after SG and a OAGB (one anastomosis gastric bypass) for recording of the gastroesophageal reflex disease (GERD) status. In the first line complication management of hemorrhage and leakages, endoscopic procedures have prevailed over surgical ones due to more causal therapeutic approaches (except cases of general peritonitis where lavage and drainages are needed). In the treatment of late complications such as dumping, anastomosis dilatation and stenosis, bariatric endoscopy provides versatile, organ-preserving solutions and continues to demonstrate a high degree of innovation. In these postoperative fields of application, especially in the treatment of late complications, specific knowledge of bariatric anatomy and physiology as well as surgical treatment options are required in addition to endoscopic expertise. The special field of bariatric endoscopy has developed and will have an own importance closely linked to the bariatric surgery.

Thermal effect of a 445 nm diode laser on five dental implant systems: an in vitro study.

The purpose of this in vitro study was to assess the thermal effect of the 445 nm diode laser on five dental implant systems. In an ailing implant protocol, five commercial dental implant systems were subjected to 445 nm diode laser energy at different wattages [W], exposure times, and modes (continuous wave [CW] vs. pulsed and contact vs. non-contact) of laser beam delivery. Scanning electron microscopy (SEM) allowed the evaluation of irradiated implant surfaces. A total of 2880 temperature response curves were recorded. The 445 nm wavelength caused temperature increases of more than 10 °C at or above the 0.8 W power level working in CW mode for 5 s and in pulsed mode at 3 W for 20 s with 10% duty cycle. Highest rises in temperature were seen in the Straumann Pure ceramic implant, lowest in the Ankylos system. SEM analysis revealed no surface alteration in all systems in non-contact mode. The applied laser is not inherently safe for the decontamination of ailing implants. From the results of this study it was concluded that different dental implant materials and geometries show different temperature response curves when subjected to 445 nm diode laser energy. Clinicians ought to be aware of this. Therefore, manufacturers of laser devices should provide implant-specific laser parameters for the decontamination process. However, both laser irradiation systems can prevent harmful rises in temperature and surface alteration when used at moderate laser parameters.

Effect of various weight loss interventions on serum NT-proBNP concentration in severe obese subjects without clinical manifest heart failure.

Obesity is associated with a "natriuretic handicap" indicated by reduced N-terminal fragment of proBNP (NT-proBNP) concentration. While gastric bypass surgery improves the natriuretic handicap, it is presently unclear if sleeve gastrectomy exhibits similar effects. We examined NT-proBNP serum concentration in n = 72 obese participants without heart failure before and 6 months after sleeve gastrectomy (n = 28), gastric bypass surgery (n = 19), and 3-month 800 kcal/day very-low calorie diet (n = 25). A significant weight loss was observed in all intervention groups. Within 6 months, NT-proBNP concentration tended to increase by a median of 44.3 pg/mL in the sleeve gastrectomy group (p = 0.07), while it remained unchanged in the other groups (all p ≥ 0.50). To gain insights into potential effectors, we additionally analyzed NT-proBNP serum concentration in n = 387 individuals with different metabolic phenotypes. Here, higher NT-proBNP levels were associated with lower nutritional fat and protein but not with carbohydrate intake. Of interest, NT-proBNP serum concentrations were inversely correlated with fasting glucose concentration in euglycemic individuals but not in individuals with prediabetes or type 2 diabetes. In conclusion, sleeve gastrectomy tended to increase NT-proBNP levels in obese individuals and might improve the obesity-associated "natriuretic handicap". Thereby, nutritional fat and protein intake and the individual glucose homeostasis might be metabolic determinants of NT-proBNP serum concentration.

Histologic improvement of NAFLD in patients with obesity after bariatric surgery based on standardized NAS (NAFLD activity score).

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder in industrialized countries. Nonalcoholic steatohepatitis is the fastest growing cause for liver failure. Bariatric surgery represents a treatment option for NAFLD with an established effect on liver histology. OBJECTIVES: We aimed to assess the impact of bariatric surgery on standardized liver histology using the NAFLD activity score. SETTING: Retrospective comparison of metabolic data before and after bariatric surgery and comparison of sleeve gastrectomy and Roux-en-Y gastric bypass. The study was performed in an academic center, the university hospital Schleswig-Holstein in Kiel, Germany. METHODS: Between 2009 and 2012, bariatric surgery was performed in 257 patients according to the national guidelines, and a liver biopsy was obtained in 150 of these patients during surgery. A follow-up biopsy was available in 53 of these patients at a median of 192 days. Liver histology was analyzed using the NAFLD activity score. In this subgroup of 53 patients an analysis of the metabolic improvement after bariatric surgery and a comparative analysis between the 2 different operative procedures was performed. RESULTS: The study cohort showed improvement of preoperative pathologic liver histology findings after operative procedures took place. Both surgery methods improved the NAFLD activity score significantly, all improvement -2.0 (confidence interval -2.5 to -1.0; P < .001); Roux-en-Y gastric bypass, improvement -1.0 (confidence interval -2.0 to -.0; P = .038); sleeve gastrectomy, improvement -2.5 (confidence interval -3.5 to -1.5; P < .001). No differences were found with regard to histologic recovery between gastric bypass and sleeve gastrectomy (P = .22). CONCLUSIONS: Bariatric surgery significantly improves NAFLD.

Hypothalamic Inflammation in Human Obesity Is Mediated by Environmental and Genetic Factors.

Obesity is associated with hypothalamic inflammation (HI) in animal models. In the current study, we examined the mediobasal hypothalamus (MBH) of 57 obese human subjects and 54 age- and sex- matched nonobese control subjects by MRI and analyzed the T2 hyperintensity as a measure of HI. Obese subjects exhibited T2 hyperintensity in the left but not the right MBH, which was strongly associated with systemic low-grade inflammation. MRS revealed the number of neurons in the left hypothalamic region to be similar in obese versus control subjects, suggesting functional but not structural impairment due to the inflammatory process. To gain mechanistic insights, we performed nutritional analysis and 16S rDNA microbiome sequencing, which showed that high-fat diet induces reduction of Parasutterella sp. in the gut, which is significantly correlated with MBH T2 hyperintensity. In addition to these environmental factors, we found subjects carrying common polymorphisms in the JNK or the MC4R gene to be more susceptible to HI. Finally, in a subgroup analysis, bariatric surgery had no effect on MBH T2 hyperintensity despite inducing significant weight loss and improvement of peripheral insulin sensitivity. In conclusion, obesity in humans is associated with HI and disturbances in the gut-brain axis, which are influenced by both environmental and genetic factors.

Obesity accelerates epigenetic aging of human liver.

Because of the dearth of biomarkers of aging, it has been difficult to test the hypothesis that obesity increases tissue age. Here we use a novel epigenetic biomarker of aging (referred to as an "epigenetic clock") to study the relationship between high body mass index (BMI) and the DNA methylation ages of human blood, liver, muscle, and adipose tissue. A significant correlation between BMI and epigenetic age acceleration could only be observed for liver (r = 0.42, P = 6.8 × 10(-4) in dataset 1 and r = 0.42, P = 1.2 × 10(-4) in dataset 2). On average, epigenetic age increased by 3.3 y for each 10 BMI units. The detected age acceleration in liver is not associated with the Nonalcoholic Fatty Liver Disease Activity Score or any of its component traits after adjustment for BMI. The 279 genes that are underexpressed in older liver samples are highly enriched (1.2 × 10(-9)) with nuclear mitochondrial genes that play a role in oxidative phosphorylation and electron transport. The epigenetic age acceleration, which is not reversible in the short term after rapid weight loss induced by bariatric surgery, may play a role in liver-related comorbidities of obesity, such as insulin resistance and liver cancer.

B Lymphocyte Stimulator (BLyS) is expressed in human adipocytes in vivo and is related to obesity but not to insulin resistance.

Inflammation and metabolism have been shown to be evolutionary linked and increasing evidence exists that pro-inflammatory factors are involved in the pathogenesis of obesity and type 2 diabetes. Until now, most data suggest that within adipose tissue these factors are secreted by cells of the innate immune system, e. g. macrophages. In the present study we demonstrate that B lymphocyte stimulator (BLyS) is increased in human obesity. In contrast to several pro-inflammatory factors, we found the source of BLyS in human adipose tissue to be the adipocytes rather than immune cells. In grade 3 obese human subjects, expression of BLyS in vivo in adipose tissue is significantly increased (p<0.001). Furthermore, BLyS serum levels are elevated in grade 3 human obesity (862.5+222.0 pg/ml vs. 543.7+60.7 pg/ml in lean controls, p<0.001) and are positively correlated to the BMI (r = 0.43, p<0.0002). In the present study, bariatric surgery significantly altered serum BLyS concentrations. In contrast, weight loss due to a very-low-calorie-formula-diet (800 kcal/d) had no such effect. To examine metabolic activity of BLyS, in a translational research approach, insulin sensitivity was measured in human subjects in vivo before and after treatment with the human recombinant anti-BLyS antibody belimumab. Since BLyS is known to promote B-cell proliferation and immunoglobulin secretion, the present data suggest that adipocytes of grade 3 obese human subjects are able to activate the adaptive immune system, suggesting that in metabolic inflammation in humans both, innate and adaptive immunity, are of pathophysiological relevance.

Metabolic signature of electrosurgical liver dissection.

BACKGROUND AND AIMS: High frequency electrosurgery has a key role in the broadening application of liver surgery. Its molecular signature, i.e. the metabolites evolving from electrocauterization which may inhibit hepatic wound healing, have not been systematically studied. METHODS: Human liver samples were thus obtained during surgery before and after electrosurgical dissection and subjected to a two-stage metabolomic screening experiment (discovery sample: N = 18, replication sample: N = 20) using gas chromatography/mass spectrometry. RESULTS: In a set of 208 chemically defined metabolites, electrosurgical dissection lead to a distinct metabolic signature resulting in a separation in the first two dimensions of a principal components analysis. Six metabolites including glycolic acid, azelaic acid, 2-n-pentylfuran, dihydroactinidiolide, 2-butenal and n-pentanal were consistently increased after electrosurgery meeting the discovery (p<2.0 × 10(-4)) and the replication thresholds (p<3.5 × 10(-3)). Azelaic acid, a lipid peroxidation product from the fragmentation of abundant sn-2 linoleoyl residues, was most abundant and increased 8.1-fold after electrosurgical liver dissection (preplication = 1.6 × 10(-4)). The corresponding phospholipid hexadecyl azelaoyl glycerophosphocholine inhibited wound healing and tissue remodelling in scratch- and proliferation assays of hepatic stellate cells and cholangiocytes, and caused apoptosis dose-dependently in vitro, which may explain in part the tissue damage due to electrosurgery. CONCLUSION: Hepatic electrosurgery generates a metabolic signature with characteristic lipid peroxidation products. Among these, azelaic acid shows a dose-dependent toxicity in liver cells and inhibits wound healing. These observations potentially pave the way for pharmacological intervention prior liver surgery to modify the metabolic response and prevent postoperative complications.

DNA methylation analysis in nonalcoholic fatty liver disease suggests distinct disease-specific and remodeling signatures after bariatric surgery.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder in industrialized countries. Liver samples from morbidly obese patients (n = 45) with all stages of NAFLD and controls (n = 18) were analyzed by array-based DNA methylation and mRNA expression profiling. NAFLD-specific expression and methylation differences were seen for nine genes coding for key enzymes in intermediate metabolism (including PC, ACLY, and PLCG1) and insulin/insulin-like signaling (including IGF1, IGFBP2, and PRKCE) and replicated by bisulfite pyrosequening (independent n = 39). Transcription factor binding sites at NAFLD-specific CpG sites were >1,000-fold enriched for ZNF274, PGC1A, and SREBP2. Intraindividual comparison of liver biopsies before and after bariatric surgery showed NAFLD-associated methylation changes to be partially reversible. Postbariatric and NAFLD-specific methylation signatures were clearly distinct both in gene ontology and transcription factor binding site analyses, with >400-fold enrichment of NRF1, HSF1, and ESRRA sites. Our findings provide an example of treatment-induced epigenetic organ remodeling in humans.

A new technique for bedside placement of enteral feeding tubes: a prospective cohort study.

INTRODUCTION: To accomplish early enteral feeding in the critically ill patient a new transnasal endoscopic approach to the placement of postpyloric feeding tubes by intensive care physicians was evaluated. METHODS: This was a prospective cohort study in 27 critically ill patients subjected to transnasal endoscopy and intubation of the pylorus. Attending intensive care physicians were trained in the handling of the new endoscope for transnasal gastroenteroscopy for two days. A jejunal feeding tube was advanced via the instrument channel and the correct position assessed by contrast radiography. The primary outcome measure was successful postpyloric placement of the tube. Secondary outcome measures were time needed for the placement, complications such as bleeding and formation of loops, and the score of the placement difficulty graded from 1 (easy) to 4 (difficult). Data are given as mean values and standard deviation. RESULTS: Out of 34 attempted jejunal tube placements, 28 tubes (82%) were placed correctly in the jejunum. The duration of the procedure was 28 ± 12 minutes. The difficulty of the tube placement was judged as follows: grade 1: 17 patients, grade 2: 8 patients, grade 3: 7 patients, grade 4: 2 patients. In three cases, the tube position was incorrect, and in another three cases, the procedure had to be aborted. In one patient bleeding occurred that required no further treatment. CONCLUSIONS: Fast and reliable transnasal insertion of postpyloric feeding tubes can be accomplished by trained intensive care physicians at the bedside using the presented procedure. This new technique may facilitate early initiation of enteral feeding in intensive care patients.