Bark Betzel

Secondary surgery after sleeve gastrectomy: Roux-en-Y gastric bypass or biliopancreatic diversion with duodenal switch

BACKGROUND Laparoscopic sleeve gastrectomy (LSG) has gained popularity as a stand-alone procedure with good short-term results for weight loss. However, in the long-term, weight regain and other complications are reported. Demand for secondary surgery is rising, partly for these reasons. OBJECTIVES To review the indications and effects of secondary surgery, biliopancreatic diversion with duodenal switch (BPD/DS) versus laparoscopic Roux-en-Y gastric bypass (LRYGB), after LSG. METHODS Data from all patients who underwent revision of LSG was retrospectively analyzed, concerning data on indications for secondary surgery, weight loss, and complications. RESULTS 43 Patients underwent secondary surgery after LSG; 25 BPD/DS and 18 LRYGB, respectively. Main indications for secondary surgery were inadequate weight loss (n = 17 [40%]) and weight regain (n = 8 [19%]). For these indications, the median excess weight loss was greater for BPD/DS (59% [range 15-113]) compared to LRYGB (23% [range -49-84]) (P = .008) after 34 months (range 14-79). In case of dysphagia or gastroesophageal reflux disease the complaints resolved after converting to LRYGB. BPD/DS patients were more likely to develop a short-term complication and vitamin deficiencies compared to LRYGB. CONCLUSIONS Secondary surgery of LSG to BPD/DS or LRYGB is feasible with slightly more complications after BPD/DS. Conversion to LRYGB is preferred in cases of dysphagia or gastroesophageal reflux disease. In cases of weight regain or insufficient weight loss after LSG, patients had better weight loss with a BPD/DS; however, this procedure has the risk of complications, such as severe vitamin deficiencies.

The impact of PPARα activation on whole genome gene expression in human precision cut liver slices

BackgroundStudies in mice have shown that PPARα is an important regulator of lipid metabolism in liver and key transcription factor involved in the adaptive response to fasting. However, much less is known about the role of PPARα in human liver. MethodsHere we set out to study the function of PPARα in human liver via analysis of whole genome gene regulation in human liver slices treated with the PPARα agonist Wy14643.ResultsQuantitative PCR indicated that PPARα is well expressed in human liver and human liver slices and that the classical PPARα targets PLIN2, VLDLR, ANGPTL4, CPT1A and PDK4 are robustly induced by PPARα activation. Transcriptomics analysis indicated that 617 genes were upregulated and 665 genes were downregulated by PPARα activation (q value < 0.05). Many genes induced by PPARα activation were involved in lipid metabolism (ACSL5, AGPAT9, FADS1, SLC27A4), xenobiotic metabolism (POR, ABCC2, CYP3A5) or the unfolded protein response, whereas most of the downregulated genes were involved in immune-related pathways. Among the most highly repressed genes upon PPARα activation were several chemokines (e.g. CXCL9-11, CCL8, CX3CL1, CXCL6), interferon γ-induced genes (e.g. IFITM1, IFIT1, IFIT2, IFIT3) and numerous other immune-related genes (e.g. TLR3, NOS2, and LCN2). Comparative analysis of gene regulation by Wy14643 between human liver slices and primary human hepatocytes showed that down-regulation of gene expression by PPARα is much better captured by liver slices as compared to primary hepatocytes. In particular, PPARα activation markedly suppressed immunity/inflammation-related genes in human liver slices but not in primary hepatocytes. Finally, several putative new target genes of PPARα were identified that were commonly induced by PPARα activation in the two human liver model systems, including TSKU, RHOF, CA12 and VSIG10L.ConclusionOur paper demonstrates the suitability and superiority of human liver slices over primary hepatocytes for studying the functional role of PPARα in human liver. Our data underscore the major role of PPARα in regulation of hepatic lipid and xenobiotic metabolism in human liver and reveal a marked immuno-suppressive/anti-inflammatory effect of PPARα in human liver slices that may be therapeutically relevant for non-alcoholic fatty liver disease.

Safety experience with the duodenal-jejunal bypass liner: an endoscopic treatment for diabetes and obesity

BACKGROUND The duodenal-jejunal bypass liner (DJBL) is a new, device-based endoscopic treatment for type 2 diabetes mellitus (T2DM) and obesity. OBJECTIVE To report serious safety events of subjects treated with the DJBL while offering a simple guideline to mitigate risk. DESIGN Single-center observational study. SETTING Tertiary referral center. PATIENTS For commercial use, patients were eligible for implantation of the DJBL when they met the following criteria: age 18 to 65 years, body mass index 28 to 45 kg/m(2), T2DM, and negative serum Helicobacter pylori test. INTERVENTIONS Endoscopic implantation of the DJBL. MAIN OUTCOME MEASUREMENTS Adverse events, serious adverse events, early explantation. RESULTS Between October 2007 and January 2014, 152 of 165 planned implantations (92%) and 94 explantations were performed in our center. Significant weight loss and improvement in T2DM and other cardiovascular parameters were achieved. Early removal of the device occurred because of persistent GI symptoms in 16 patients (11%). Serious adverse events were observed in a subset of patients: 7 GI bleeds, 5 of which required early removal; 2 cases of pancreatitis; 1 case of hepatic abscess; and 1 obstruction of the sleeve. Explantation resulted in an esophageal tear in 2 cases. LIMITATIONS Single-center study. CONCLUSION The DJBL improves glycemic control while causing weight loss. The safety profile of the DJBL demonstrates a reasonable tolerability profile. However, serious safety adverse events can occur. Patient selection, expert use of the device at placement and removal, and the supportive care of an experienced multidisciplinary team are key for safe and effective use of the DJBL.

A new noninvasive technique for estimating hepatic triglyceride: will liver biopsy become redundant in diagnosing non-alcoholic fatty liver disease?

Obesity and metabolic syndrome are healthcare problems that continue to rise in frequency worldwide. Both phenotypes are a strong predictor for development of liver steatosis in the context of non-alcoholic fatty liver disease or non-alcoholic steatohepatitis. Ultrasound may detect steatosis, but its sensitivity is limited and liver biopsy is still considered to be the gold standard. Less invasive techniques that accurately quantify liver steatosis are warranted. Jiménez-Agüero and colleagues propose that multi-echo magnetic resonance imaging might be such a diagnostic tool. They validated multi-echo magnetic resonance imaging with measured hepatic triglyceride concentration. Their results show that this innovative technique measures the grade of steatosis in different clinical situations. Therefore, multi-echo magnetic resonance imaging might be considered for monitoring liver steatosis as an intermediate endpoint. Wide clinical applicability is limited though, as it does not allow differentiation between non-alcoholic fatty liver disease and non-alcoholic steatohepatitis.

Acute pancreatitis as an adverse event in patients with the duodenal-jejunal bypass liner

Placement of the duodenal-jejunal bypass liner (DJBL) is a minimally invasive technique for the management of patients with type 2 diabetes mellitus and obesity. Acute pancreatitis was seen in 5 of 167 patients (3 %) in our series. It is suggested that acute pancreatitis in patients with the DJBL results from either direct blockage or edema of the major duodenal papilla, which may be caused by the following: migration of the anchor of the DJBL, accumulation of food debris between the liner and the duodenal wall, or reflux of duodenal contents into the pancreatic duct due to intraluminal hypertension caused by the liner. Early removal of the DJBL resulted in fast and complete recovery, whereas delayed diagnosis and removal led to severe, necrotizing acute pancreatitis.

Adverse Events of the Duodenal-Jejunal Bypass Liner: a Systematic Review

A systematic review was conducted on adverse events (AEs) associated with the use of the duodenal-jejunal bypass liner (DJBL). PubMed, EMBASE, and Cochrane library were searched up to January 2018. The quality of reporting AEs was determined by the McHarm questionnaire and the risk of bias by the Newcastle-Ottawa scale. Thirty-eight studies were included. The comparability of the studies was low and the McHarm questionnaire showed incompleteness for most parameters in all studies. A total of 891 AEs were reported in 1056 patients. Thirty-three AEs (3.7%) were classified as severe, including hepatic abscess and esophageal perforation. The anchor of the DJBL caused or likely caused 85% of the SAEs. To improve the safety margin of the DJBL, adjustments to the anchoring system are needed.