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1.  The impact of PPARα activation on whole genome gene expression in human precision cut liver slices 
BMC Genomics  2015;16:760.
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.
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.
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.
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.
Electronic supplementary material
The online version of this article (doi:10.1186/s12864-015-1969-3) contains supplementary material, which is available to authorized users.
PMCID: PMC4599789  PMID: 26449539
Precision cut liver slices; PPARα; Human liver; Transcriptomics
2.  Intragastric band erosion: Experiences with gastrointestinal endoscopic removal 
AIM: To remove the migrated bands using a gastrointestinal endoscopic approach. Little is published on complications that can occur.
METHODS: From June 2006 to June 2010, eight patients developed intragastric band migration. Two patients had received their AGB in a different hospital, the remaining six were operated by the same surgeon. In all patients gastrointestinal endoscopic removal of the band was attempted by two individual gastroenterologists. Clinical signs of band migration were: persisted nausea, abdominal pain, weight gain, recurrent infection of the port and tubing system and hematemesis.
RESULTS: In four patients removal was performed without complications. In two patients extracting the cleaved gastric band into the stomach appeared impossible. The two remaining patients presented with acute hematemesis and melena. One of these patients was readmitted with hematemesis. The other patient started bleeding during the gastroscopy and was converted to a laparoscopy in which one of the branches of the left gastric artery was oversewn.
CONCLUSION: Band migration after gastric banding can be life threatening. Gastrointestinal endoscopic removal is a feasible technique that holds the promise of fast reconvalescence.
PMCID: PMC4316098  PMID: 25663775
Morbid obesity; Adjustable gastric band; Migration; Gastroscopy; Gastrointestinal endoscopic device removal
3.  Optimization of Vitamin Suppletion After Roux-En-Y Gastric Bypass Surgery Can Lower Postoperative Deficiencies 
Medicine  2014;93(25):e169.
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 ± 70.1 μg/L) and vitamin B12 (−45.9 ± 150.3 pmol/L) over 12 months, whereas in WLS Forte patients, ferritin remained stable (+3.2 ± 93.2 μg/L) and vitamin B12 increased significantly (+55.1 ± 144.2 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.
PMCID: PMC4616370  PMID: 25437032
4.  Duodenal-jejunal bypass liner implantation provokes rapid weight loss and improved glycemic control, accompanied by elevated fasting ghrelin levels 
Endoscopy International Open  2014;2(1):E21-E27.
Background and study aims: Endoscopic implantation of a duodenal-jejunal bypass liner (DJBL) is a novel bariatric technique to induce weight loss and remission of type 2 diabetes mellitus. Placement of the DJBL mimics the bypass component of the Roux-en-Y gastric bypass (RYGB) procedure. In this observational study, we evaluated improvement of glycemic control and weight loss in the course of the treatment (0 – 24 weeks after DJBL implantation) and analyzed accompanying gut hormone responses.
Patients and methods: 12 obese individuals with type 2 diabetes were selected for DJBL implantation. Body weight, fat mass, and fasting plasma levels of glucose, insulin, C-peptide, and glycated hemoglobin (HbA1c), were analyzed at 0, 1, 4 and 24 weeks post-implant. Fasting ghrelin, gastric inhibitory peptide (GIP), and glucagon-like peptide (GLP-1) were determined at 0, 1 and 4 weeks post-implant.
Results: Besides significant weight loss, fat mass, fasting insulin, and homeostasis model assessment-estimated insulin resistance (HOMA-IR) index were also significantly decreased after DJBL implantation and a 42 % reduction was found in diabetes medication (P < 0.05). The fasting GLP-1 response in the first 4 weeks post-implant was significantly correlated with the fasting insulin and HOMA-IR response. Fasting ghrelin was found to be significantly elevated, in contrast to the decrease in ghrelin that is found after RYGB surgery.
Conclusions: DJBL implantation provoked significant weight loss, a decrease in fat mass, and an early remission of type 2 diabetes, comparable to results seen after RYGB surgery. Gut hormone analyses revealed a potential role of fasting GLP-1 in early remission of type 2 diabetes. Interestingly, the DJBL-induced elevation of ghrelin contradicts the suggested role of reduced ghrelin levels after RYGB in improvement of glycemic control.
PMCID: PMC4423279  PMID: 26134609
5.  Striatal dopamine receptor binding in morbidly obese women before and after gastric bypass surgery and its relationship with insulin sensitivity 
Diabetologia  2014;57(5):1078-1080.
PMCID: PMC3980032  PMID: 24500343
Dopamine receptor; Gastric bypass surgery; Insulin sensitivity; Obesity; SPECT; Striatal dopamine; Weight loss
6.  A multicenter randomized controlled trial evaluating the effect of small stitches on the incidence of incisional hernia in midline incisions 
BMC Surgery  2011;11:20.
The median laparotomy is frequently used by abdominal surgeons to gain rapid and wide access to the abdominal cavity with minimal damage to nerves, vascular structures and muscles of the abdominal wall. However, incisional hernia remains the most common complication after median laparotomy, with reported incidences varying between 2-20%. Recent clinical and experimental data showed a continuous suture technique with many small tissue bites in the aponeurosis only, is possibly more effective in the prevention of incisional hernia when compared to the common used large bite technique or mass closure.
The STITCH trial is a double-blinded multicenter randomized controlled trial designed to compare a standardized large bite technique with a standardized small bites technique. The main objective is to compare both suture techniques for incidence of incisional hernia after one year. Secondary outcomes will include postoperative complications, direct costs, indirect costs and quality of life.
A total of 576 patients will be randomized between a standardized small bites or large bites technique. At least 10 departments of general surgery and two departments of oncological gynaecology will participate in this trial. Both techniques have a standardized amount of stitches per cm wound length and suture length wound length ratio's are calculated in each patient. Follow up will be at 1 month for wound infection and 1 year for incisional hernia. Ultrasound examinations will be performed at both time points to measure the distance between the rectus muscles (at 3 points) and to objectify presence or absence of incisional hernia. Patients, investigators and radiologists will be blinded during follow up, although the surgeon can not be blinded during the surgical procedure.
The STITCH trial will provide level 1b evidence to support the preference for either a continuous suture technique with many small tissue bites in the aponeurosis only or for the commonly used large bites technique.
Trial registration NCT01132209
PMCID: PMC3182877  PMID: 21871072
7.  The Gastric Sleeve: Losing Weight as Fast as Micronutrients? 
Obesity Surgery  2010;21(2):207-211.
Recently, the laparoscopic sleeve gastrectomy (LSG) has become popular as a single-stage procedure for the treatment of morbid obesity and its co-morbidities. However, the incidence of micronutrient deficiencies after LSG have hardly been researched.
From January 2005 to October 2008, 60 patients underwent LSG. All patients were instructed to take daily vitamin supplements. Patients were tested for micronutrient deficiencies 6 and 12 months after surgery.
Anemia was diagnosed in 14 (26%) patients. Iron, folic acid, and vitamin B12 deficiency was found in 23 (43%), eight (15%), and five (9%) patients, respectively. Vitamin D and albumin deficiency was diagnosed in 21 (39%) and eight (15%) patients. Hypervitaminosis A, B1, and B6 were diagnosed in 26 (48%), 17 (31%), and 13 (30%) patients, respectively.
Due to inadequate intake and uptake of micronutrients, patients who underwent LSG are at serious risk for developing micronutrient deficiencies. Moreover, some vitamins seem to increase to chronic elevated levels with possible complications in the long-term. Multivitamins and calcium tablets should be regarded only as a minimum and supplements especially for iron, vitamin B12, vitamin D, and calcium should be added to this regimen based on regular blood testing.
PMCID: PMC3021197  PMID: 21088925
Gastric sleeve; LSG; Anemia; Micronutrients; Deficiency; Hypervitaminosis; Iron; Calcium; Folate; Vitamin A; Vitamin B1; Vitamin B6; Vitamin B12; Vitamin D
8.  Reply to: ‘Re: “The invisible cholecystectomy”’ 
Surgical Endoscopy  2008;22(7):1739-1740.
PMCID: PMC2422864  PMID: 18443864

Results 1-8 (8)