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.

The Effect of 6 and 12 months Duodenal-Jejunal Bypass Liner Treatment on Obesity and Type 2 Diabetes: a Crossover Cohort Study.

OBJECTIVE: The aim of this research was to study the duodenal-jejunal bypass liner (DJBL) treatment for obesity and type 2 diabetes mellitus (T2DM) in patients after dietary treatment in a cross-over design. BACKGROUND: DJBL treatment has been proven effective for treatment of obesity and T2DM. However, data on safety and efficacy of a 12-month DJBL treatment is limited. METHODS: In 2014, our research group reported on a multicenter randomized clinical trial. Patients were randomized to DJBL or dietary treatment (control group). Twenty-eight patients crossed over after their dietary treatment and received up to 12 months of DJBL treatment. Patient visits were conducted at baseline, during DJBL treatment (1 week, 1-6, 9, 12 months) and 6 months after removal of the liner. Patients underwent a standard physical examination, blood sampling, assessment of adverse events, nutritional and diabetes counseling, and a standardized meal tolerance test. RESULTS: Of the 28 patients included in this study, 24 patients completed 6 months of treatment. Eighteen patients were extended to 12 months of DJBL treatment; 13 patients completed this treatment period. After 6 months of DJBL treatment, a significant increase in excess weight loss (EWL) and decrease in weight, BMI, HbA1c, fasting glucose, cholesterol, HDL and LDL improved significantly. After 12 months of DJBL treatment, these parameters stabilized. CONCLUSIONS: The DJBL is an effective, minimally invasive treatment option. Even after successful treatment with dietary restrictions, the DJBL is still capable of significantly reducing weight and improving cardiovascular and type 2 diabetes mellitus parameters in obese patients.

Weight reduction and improvement in diabetes by the duodenal-jejunal bypass liner: a 198 patient cohort study.

BACKGROUND: The duodenal-jejunal bypass liner (DJBL) is an endoscopic treatment for patients with type 2 diabetes mellitus (T2DM) and (morbid) obesity. The aim of the current study was to determine its efficacy and safety profile. METHODS: Inclusion criteria for treatment with a DJBL were: age 18-70 years, BMI 28-45 kg/m2, and T2DM with a HbA1c > 48 mmol/mol. Primary outcomes were changes in HbA1c and body weight. Secondary outcomes included changes in blood pressure, lipids, and anti-diabetic medication. Predictive factors for success of treatment with the DJBL were determined. RESULTS: Between 2011 and 2014, 185 out of 198 patients successfully underwent a DJBL implantation procedure, with an intended implantation time of 12 months. In these 185 patients, body weight decreased by 12.8 ± 8.0 kg (total body weight loss of 11.9 ± 6.9 %, p < 0.001), HbA1c decreased from 67 to 61 mmol/mol (p < 0.001) despite a reduction in anti-diabetic medication, and blood pressure and serum lipid levels all decreased. In total, 57 (31 %) DJBLs were explanted early after a median duration of 33 weeks. Adverse events occurred in 17 % of patients. C-peptide ≥1.0 nmol/L and body weight ≥107 kg at screening were independent predictive factors for success. CONCLUSIONS: Treatment with the DJBL in T2DM patients with (morbid) obesity results in improvement in glucose control, a reduction in anti-diabetic medication, and significant weight loss. The largest changes are observed within the first 3-6 months. Initial C-peptide levels and body weight may help to select patients with the greatest chance of success.

Changes in glycemic control and body weight after explantation of the duodenal-jejunal bypass liner.

BACKGROUND AND AIMS: The duodenal-jejunal bypass liner (DJBL) is an endoscopic device that induces weight loss and improves glycemic control in patients with type 2 diabetes mellitus (T2DM). The aim of the current study was to assess the effects of DJBL explantation on glycemic control and body weight. METHODS: This prospective, observational study included only patients with T2DM who had the DJBL implanted for at least 6 months and had a follow-up of at least 12 months after explantation. The primary endpoints were changes in glycosylated hemoglobin A1c (HbA1c) and body weight during the 12 months after explantation. Secondary endpoints were changes in fasting plasma glucose, blood pressure, and plasma lipid levels. RESULTS: In total, 59 patients completed the 12-month follow-up after explantation. During this period body weight increased by 5.6 (standard deviation, 6.4) kg (P < .001) and HbA1c rose from 65 (SD 17) to 70 (SD 20) mmol/mol (P < .001). However, body weight remained 8.0 (SD 8.6) kg (P < .001) lower than before implantation, that is, corresponding to a net total body weight loss of 7.4% (SD 7.6) (P < .001). Although HbA1c was significantly higher 12 months after explantation compared with baseline and the mean daily dose of insulin used was comparable, the number of patients on insulin remained significantly lower than before implantation. CONCLUSIONS: Explantation of the DJBL is associated with weight gain and worsening of glycemic control, although some beneficial effects remained detectable 12 months after explantation. A change in strategy is needed to preserve the beneficial effects of DJBL treatment. (Clinical trial registration number: 746∖100111.).

Gene expression profiling in human precision cut liver slices in response to the FXR agonist obeticholic acid.

BACKGROUND & AIMS: The bile acid-activated farnesoid X receptor (FXR) is a nuclear receptor regulating bile acid, glucose and cholesterol homeostasis. Obeticholic acid (OCA), a promising drug for the treatment of non-alcoholic steatohepatitis (NASH) and type 2 diabetes, activates FXR. Mouse studies demonstrated that FXR activation by OCA alters hepatic expression of many genes. However, no data are available on the effects of OCA in the human liver. Here we generated gene expression profiles in human precision cut liver slices (hPCLS) after treatment with OCA. METHODS: hPCLS were incubated with OCA for 24 h. Wild-type or FXR(-/-) mice received OCA or vehicle by oral gavage for 7 days. RESULTS: Transcriptomic analysis showed that well-known FXR target genes, including NR0B2 (SHP), ABCB11 (BSEP), SLC51A (OSTα) and SLC51B (OSTß), and ABCB4 (MDR3) are regulated by OCA in hPCLS. Ingenuity pathway analysis confirmed that 'FXR/RXR activation' is the most significantly changed pathway upon OCA treatment. Comparison of gene expression profiles in hPCLS and mouse livers identified 18 common potential FXR targets. ChIP-sequencing in mouse liver confirmed FXR binding to IR1 sequences of Akap13, Cgnl1, Dyrk3, Pdia5, Ppp1r3b and Tbx6. CONCLUSIONS: Our study shows that hPCLS respond to OCA treatment by upregulating well-known FXR target genes, demonstrating its suitability to study FXR-mediated gene regulation. We identified six novel bona-fide FXR target genes in both mouse and human liver. Finally, we discuss a possible explanation for changes in high or low density lipoprotein observed in NASH and primary biliary cholangitis patients treated with OCA based on the genomic expression profile in hPCLS.

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

BACKGROUND: Studies 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. METHODS: Here 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. RESULTS: Quantitative 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. CONCLUSION: Our 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.

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.

Randomized controlled trial of transoral incisionless fundoplication vs. proton pump inhibitors for treatment of gastroesophageal reflux disease.

OBJECTIVES: Transoral incisionless fundoplication (TIF) was developed in an attempt to create a minimally invasive endoscopic procedure that mimics antireflux surgery. The objective of this trial was to evaluate effectiveness of TIF compared with proton pump inhibition in a population consisting of gastroesophageal reflux disease (GERD) patients controlled with proton pump inhibitors (PPIs) who opted for an endoscopic intervention over lifelong drug dependence. METHODS: Patients with chronic GERD were randomized (2:1) for TIF or continuation of PPI therapy. American Society of Anesthesiologists >2, body mass index >35 kg/m(2), hiatal hernia >2 cm, and esophageal motility disorders were exclusion criteria. Primary outcome measure was GERD-related quality of life. Secondary outcome measures were esophageal acid exposure, number of reflux episodes, PPI usage, appearance of the gastroesophageal valve, and healing of reflux esophagitis. Crossover for the PPI group was allowed after 6 months. RESULTS: A total of 60 patients (TIF n=40, PPI n=20, mean body mass index 26 kg/m(2), 37 male) were included. At 6 months, GERD symptoms were more improved in the TIF group compared with the PPI group (P<0.001), with a similar improvement of distal esophageal acid exposure (P=0.228) compared with baseline. The pH normalization for TIF group and PPI group was 50% and 63%, respectively. All patients allocated for PPI treatment opted for crossover. At 12 months, quality of life remained improved after TIF compared with baseline (P<0.05), but no improvement in esophageal acid exposure compared with baseline was found (P=0.171) and normalization of pH was accomplished in only 29% in conjunction with deteriorated valve appearances at endoscopy and resumption of PPIs in 61%. CONCLUSION: Although TIF resulted in an improved GERD-related quality of life and produced a short-term improvement of the antireflux barrier in a selected group of GERD patients, no long-term objective reflux control was achieved.

Subclinical hypothyroidism and its relation to obesity in patients before and after Roux-en-Y gastric bypass.

BACKGROUND: Subclinical hypothyroidism (SH), defined as a raised serum thyroid-stimulating hormone (TSH) with a normal free thyroxine (FT4), is occasionally observed in morbidly obese patients. OBJECTIVES: It is currently not known whether thyroid hormone treatment is indicated. The aim of the present study was to assess the changes in thyroid hormone levels in thyroxine-naïve patients with SH in response to weight loss induced by Roux-en-Y gastric bypass (RYGB). SETTING: General hospital specialized in bariatric surgery. METHODS: Serum levels of TSH and FT4 were measured at baseline in 503 patients presenting for RYGB. In patients diagnosed with SH, these measurements were repeated 12 months postoperatively. RESULTS: SH de novo was present in 71 out of 503 patients (14.1%). One-year follow-up was available in 61 out of 71 patients (86%). TSH level >10 mU/L was observed in 3 patients (.5%). RYGB induced a decrease in BMI from 47±8 kg/m(2) to 33±6 kg/m(2) at 12-month follow-up (P<.001), and this was associated with a decrease in TSH from 5.8±2.0 to 2.8±1.3 mU/L (P<.001) and a decrease in FT4 from 15.2±2.1 to 13.9±2.3 pmol/L (P<.001), respectively. SH completely resolved in 53 (87%) of the de novo cases. CONCLUSION: The prevalence of SH de novo is high in morbidly obese patients. After RYGB it resolves in about 90% of patients. This high degree of spontaneous recovery suggests that follow-up alone is sufficient in the majority of patients.

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.

Vitamin and Mineral Deficiencies After Biliopancreatic Diversion and Biliopancreatic Diversion with Duodenal Switch--the Rule Rather than the Exception.

INTRODUCTION: Malabsorptive bariatric procedures, like the biliopancreatic diversion (BPD) and BPD with duodenal switch (BPD/DS), have excellent results in terms of weight loss. However, these malabsorptive techniques are associated with severe malnutrition and vitamin deficiencies. The aim of this study was to evaluate the vitamin and mineral status after BPD and BPD/DS in the long term. METHODS: All patients who underwent BPD or BPD/DS were selected and invited for an additional follow-up (FU) visit, including blood sampling for vitamin and mineral levels. RESULTS: Forty patients completed the blood sampling with a median FU of 42 (range 12-90) months. At that time, all patients used some kind of supplementation. However, 93 % of all patients were diagnosed with a deficiency. There were no significant differences in mean serum level vitamins and minerals between BPD and BPD/DS. Forty-three per cent of the patients were anaemic, and 40 % had an iron deficiency (ID). High deficiency rates for fat-soluble vitamins were present: vitamin A in 28 %, vitamin D in 60 %, vitamin E in 10 % and vitamin K in 60 % of the patients. Hypervitaminosis was found in 43 % of the patients for vitamin B1 and in 50 % for vitamin B6. CONCLUSION: High numbers of vitamin and mineral deficiencies were found after BPD and BPD/DS despite vitamin supplementation. Anaemia, ID and deficiencies for fat-soluble vitamins are frequently diagnosed. Repeated monitoring is necessary to detect deficiencies at an early stage. Taking all of this into consideration, a stringent multivitamin supplementation regimen should be implemented after malabsorptive procedures.

Effectiveness and Safety of Sleeve Gastrectomy, Gastric Bypass, and Adjustable Gastric Banding in Morbidly Obese Patients: a Multicenter, Retrospective, Matched Cohort Study.

BACKGROUND: Laparoscopic adjustable gastric band (LAGB), laparoscopic sleeve gastrectomy (LSG), and laparoscopic Roux-en-Y gastric bypass (LRYGB) are the most performed procedures worldwide (92 %) nowadays. However, comparative clinical trials are scarce in literature. The objective of this study was to compare the effectiveness and safety of the three most performed bariatric procedures. METHODS: A multicenter, retrospective, matched cohort study was conducted. Patients were eligible for analysis when a primary procedure was performed between 2007 and 2010 in one of the two specialized bariatric centers. Primary outcome was weight loss, expressed in the percentage excess weight loss (%EWL). Secondary outcome parameters are hospital stay, complication rate, and revisional surgery. RESULTS: In total, 735 patients, 245 in each group, were included for analysis. The groups were comparable for age and gender after matching. Mean postoperative follow-up was 3.1 ± 1.2 years. LAGB patients showed less %EWL compared to LSG and LRYGB at all postoperative follow-up visits. LRYGB showed a %EWL of 71 ± 20 % compared to LSG (76 ± 23 %; p=0.008) after 1-year follow-up; thereafter, no significant difference was observed. After 3 years of follow-up, LAGB showed a higher complication rate compared to LSG and LRYGB (p<0.05). Revisional surgery after LAGB was needed in 21 %, while 9 % of the LSG underwent conversion to RYGB. CONCLUSIONS: LRYGB is a safe and effective treatment in morbid obese patients with good long-term outcomes. LSG seems to be an appropriate alternative as a definitive procedure, in terms of weight reduction and complication rate. LAGB is inferior to both LRYGB and LSG.

Optimization of vitamin suppletion after Roux-en-Y gastric bypass surgery can lower postoperative deficiencies: a randomized controlled trial.

Iron, vitamin B12, and folic acid deficiencies are among the most common deficiencies occurring after laparoscopic Roux-en-Y gastric bypass (LRYGB). The present study evaluates the effectiveness of a specially designed multivitamin supplement (WLS Forte, FitForMe, Rotterdam, the Netherlands) specifically developed for LRYGB patients.A triple-blind, randomized, 12-month study was conducted comparing WLS forte with a standard multivitamin supplement (sMVS) containing approximately 100% of the recommended daily allowance (RDA) for iron, vitamin B12, and folic acid. WLS Forte contains vitamin B12 14000% RDA, iron 500% RDA, and folic acid 300% RDA.In total, 148 patients (74 in each group) underwent a LRYGB procedure. Baseline characteristics were similar for both groups. Per protocol analysis demonstrated that sMVS treatment was associated with a decline in ferritin (-24.4 ±â€Š70.1 µg/L) and vitamin B12 (-45.9 ±â€Š150.3 pmol/L) over 12 months, whereas in WLS Forte patients, ferritin remained stable (+3.2 ±â€Š93.2 µg/L) and vitamin B12 increased significantly (+55.1 ±â€Š144.2 pmol/L). The number of patients developing ferritin or vitamin B12 deficiency was significantly lower with WLS Forte compared with sMVS (P < 0.05). Iron deficiency (ID) was reduced by 88% after WLS Forte compared with sMVS. Adverse events related to supplement use did not occur.An optimized multivitamin supplement is safe and reduces the development of iron and vitamin B12 deficiencies after LRYGB.

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.

The feasibility of delivering a duodenal-jejunal bypass liner (EndoBarrier) endoscopically with patients under conscious sedation.

BACKGROUND: The endoscopically placed duodenal-jejunal bypass liner (DJBL) or EndoBarrier gastrointestinal liner has been designed for the treatment of type 2 diabetes mellitus and simultaneous achievement of weight loss by obese patients. This study was performed to determine the safety, efficacy, and feasibility of delivering the DJBL with the patient under conscious sedation (CS). The primary end points of the study were safety and complications. The secondary end points were delivery time (min), amount of propofol (mg) used, and the total hospital stay (h). METHODS: This prospective study compared placement of the DJBL with the patient under propofol sedation and placement with the patient under general anesthesia (GA). The study included 56 patients, with 28 patients in each group. RESULTS: Both groups were comparable in terms of age, gender, and body mass index. All the devices were placed successfully, and no complications occurred in either group. Comparison of the CS group with the GA group respectively showed a mean total operation time of 29 versus 56 min, a mean propofol use of 170 versus 258 mg, and a mean hospital stay of 11 versus 22 h. CONCLUSION: Delivery of the DJBL to patients under CS is feasible, safe, and efficient in terms of time and cost. Because of possible complications during the procedure, the authors recommend placement of the DJBL with the patient under CS in proximity to the operating room.