A systems biology approach to understand gut microbiota and host metabolism in morbid obesity: design of the BARIA Longitudinal Cohort Study.

INTRODUCTION: Prevalence of obesity and associated diseases, including type 2 diabetes mellitus, dyslipidaemia and non-alcoholic fatty liver disease (NAFLD), are increasing. Underlying mechanisms, especially in humans, are unclear. Bariatric surgery provides the unique opportunity to obtain biopsies and portal vein blood-samples. METHODS: The BARIA Study aims to assess how microbiota and their metabolites affect transcription in key tissues and clinical outcome in obese subjects and how baseline anthropometric and metabolic characteristics determine weight loss and glucose homeostasis after bariatric surgery. We phenotype patients undergoing bariatric surgery (predominantly laparoscopic Roux-en-Y gastric bypass), before weight loss, with biometrics, dietary and psychological questionnaires, mixed meal test (MMT) and collect fecal-samples and intra-operative biopsies from liver, adipose tissues and jejunum. We aim to include 1500 patients. A subset (approximately 25%) will undergo intra-operative portal vein blood-sampling. Fecal-samples are analyzed with shotgun metagenomics and targeted metabolomics, fasted and postprandial plasma-samples are subjected to metabolomics, and RNA is extracted from the tissues for RNAseq-analyses. Data will be integrated using state-of-the-art neuronal networks and metabolic modeling. Patient follow-up will be ten years. RESULTS: Preoperative MMT of 170 patients were analysed and clear differences were observed in glucose homeostasis between individuals. Repeated MMT in 10 patients showed satisfactory intra-individual reproducibility, with differences in plasma glucose, insulin and triglycerides within 20% of the mean difference. CONCLUSION: The BARIA study can add more understanding in how gut-microbiota affect metabolism, especially with regard to obesity, glucose metabolism and NAFLD. Identification of key factors may provide diagnostic and therapeutic leads to control the obesity-associated disease epidemic.

Lactose after Roux-en-Y gastric bypass for morbid obesity, is it a problem?

BACKGROUND: Roux-en-Y gastric bypass (RYGB) can cause multiple food intolerances and gastrointestinal complaints are frequently reported after dairy consumption. We aimed to determine the prevalence of lactose malabsorption and intolerance, and complaints associated with dairy consumption in daily life, before and after RYGB. METHOD: The lactose breath test (LBT) and lactose tolerance test (LTT) was performed in 84 patients awaiting RYGB surgery and 84 patients after surgery. Gastrointestinal symptoms at baseline and after testing were recorded. Lactose malabsorption was defined as a positive LBT and/or LTT. Lactose intolerance as a positive test combined with an increase of gastrointestinal complains. Dairy consumption in daily life and successive gastrointestinal complaints were registered via a questionnaire. Results of preoperative and postoperative patients were compared. RESULTS: Lactose malabsorption was present in 15 (17.9%) of the preoperative patients and in 25 (29.8%) of the postoperative patients (OR 2.46; 95%CI: 1.08-5.59; p = .03). Of the preoperative patients 6 (7.1%) patients met the criteria for lactose intolerance, compared to 8 (9.5%) patients in the postoperative group (OR 1.48; 95%CI 0.48-4.57; p = .50). Twelve (14.3%) preoperative patients indicated to have gastrointestinal complaints after dairy consumption in daily life versus 45 (53.6%) postoperative patients (p < .01). CONCLUSION: This study shows no increase in patients with proven lactose intolerance after RYGB compared to preoperative patients. Gastrointestinal complaints after dairy consumption in daily life were far more frequently reported by RYGB patients. It is unlikely that all reported gastrointestinal complaints are actually caused by lactose. Other ingredients in dairy, like fat, are possibly contributory.

Meta-analysis of internal herniation after gastric bypass surgery.

BACKGROUND: The aim of this study was to provide a systematic and quantitative summary of the association between laparoscopic Roux-en-Y gastric bypass (LRYGB) and the reported incidence of internal herniation (IH). The route of the Roux limb and closure of mesenteric and/or mesocolonic defects are described as factors of influence. METHODS: MEDLINE, Embase, the Cochrane Library and Web of Science were searched for relevant literature, references and citations according to the PRISMA statement. Two independent reviewers selected studies that evaluated incidence of IH after LRYGB and possible techniques for prevention. Data were pooled by route of the Roux limb and closure/non-closure of the mesenteric and/or mesocolonic defects. RESULTS: Forty-five articles included data on 31 320 patients. Lowest IH incidence was in the antecolic group, with closure of all defects (1 per cent; P < 0·001), followed by the antecolic group, with all defects left open and the retrocolic group with closure of the mesenteric and mesocolonic defect (both 2 per cent; P < 0·001). The incidence of IH was highest in the antecolic group, with closure of the jejunal defect, and in the retrocolic group, with closure of all defects (both 3 per cent). CONCLUSION: The present systematic review includes a random-effects meta-analysis. The antecolic procedure, with closure of both the mesenteric and Petersen defects, has the lowest internal herniation incidence following laparoscopic Roux-en-Y gastric bypass.

The DULK (Dutch leakage) and modified DULK score compared: actively seek the leak.

AIM: A standardized postoperative score, the DULK (Dutch leakage) score, has been demonstrated to be a useful clinical tool in the diagnosis of anastomotic leakage. It is complicated, however, and a simplification (the modified DULK score) based on fewer parameters derived from multiple logistic regression analyses has been developed. These include clinical condition, abdominal pain not localized at the wound, C-reactive protein level and respiratory rate. The accuracy of each was compared. METHOD: Data of all patients from five Dutch centres operated on between 16 October 2007 and 1 November 2009 with an anastomosis in the colon or rectum were entered into a prospectively maintained database. RESULTS: In total, 782 patients were included of whom 81 (10.4%) had a clinically relevant anastomotic leakage. The DULK score gave an overall sensitivity of 97% for anastomotic leakage, overall specificity of 53%, a positive predictive value (PPV) of 16% and a negative predictive value (NPV) of 99%. The modified DULK score used clinical condition, abdominal pain not localized at the wound, C-reactive protein level and respiratory rate. With at least one parameter present, overall sensitivity was 97%, overall specificity 57%, PPV 17% and NPV 99.5%. With at least two points PPV was 41% and with three points 57%. CONCLUSION: Both the original and modified DULK scores are useful for the early diagnosis of clinically relevant anastomotic leakage. The modified DULK score offers the benefit of fewer parameters and so can easily be used in a clinical environment to estimate the likelihood of anastomotic leakage. However, the early diagnosis of anastomotic leakage remains difficult.

Gastric bypass and abdominal pain: think of Petersen hernia.

BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) is one of the most commonly performed bariatric surgical procedures. A laparoscopic gastric bypass is associated with specific complications: internal herniation is one of these. CASE REPORT: A 47-year-old woman had undergone a laparoscopic Roux-en-Y gastric bypass (LRYGB) 18 months before presentation at our emergency department with mild abdominal complaints. Physical examination showed signs of an ileus in the absence of an acute abdomen. Laboratory investigations revealed no abnormalities (CRP 2.0 mg/L, white blood count 6.3 x 109/L). During admission, there was clinical deterioration on the third day. Emergency laparotomy was performed. An internal herniation through Petersen's space was found that strangulated and perforated the small bowel. A resection with primary anastomosis and closure of the defects was performed. CONCLUSION: Diagnosing an internal herniation through Petersen's space is difficult due to the nonspecific clinical presentation. The interpretation of the CT scan poses another diagnostic challenge. This sign is present in 74% of the cases with this herniation. A missed diagnosis of internal herniation may cause potentially serious complications. A patient with a gastric bypass who experiences intermittent abdominal complaints should undergo laparoscopy to rule out internal herniation.

The effects of laparoscopic Roux-en-Y gastric bypass and one-anastomosis gastric bypass on glycemic control and remission of type 2 diabetes mellitus: study protocol for a multi-center randomized controlled trial (the DIABAR-trial).

BACKGROUND: Metabolic surgery induces rapid remission of type 2 diabetes mellitus (T2DM). There is a paucity of high level evidence comparing the efficacy of the laparoscopic Roux-en-Y gastric bypass (RYGB) and the laparoscopic one-anastomosis gastric bypass (OAGB) in glycemic control. Also, the mechanisms that drive the conversion of T2DM in severe obese subjects to euglycemia are poorly understood. METHODS: The DIABAR-trial is an open, multi-center, randomized controlled clinical trial with 10 years follow-up which will be performed in 220 severely obese patients, diagnosed with T2DM and treated with glucose-lowering agents. Patients will be randomized in a 1:1 ratio to undergo RYGB or OAGB. The primary outcome is glycemic control at 12 months follow-up. Secondary outcome measures are diverse and include weight loss, surgical complications, psychologic status and quality of life, dietary behavior, gastrointestinal symptoms, repetitive bloodwork to identify changes over time, glucose tolerance and insulin sensitivity as measured by mixed meal tests, remission of T2DM, presence of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis in liver biopsy, oral and fecal microbiome, cardiovascular performance, composition of bile acids, and the tendency to develop gallstones. DISCUSSION: The DIABAR-trial is one of the few randomized controlled trials primarily aimed to evaluate the glycemic response after the RYGB and OAGB in severe obese patients diagnosed with T2DM. Secondary aims of the trial are to contribute to a deeper understanding of the mechanisms that drive the remission of T2DM in severe obese patients by identification of microbial, immunological, and metabolic markers for metabolic response and to compare complications and side effects of RYGB and OAGB. TRIAL REGISTRATION: ClinicalTrials.gov NCT03330756 ; date first registered: October 13, 2017.

[Intensive lifestyle interventions: are they effective against obesity?] / De gecombineerde leefstijlinterventie.

The intensive lifestyle intervention (ILI) has recently become part of the reimbursed care in the Netherlands. What is the value of the ILI in the treatment of obesity and diabetes? Large clinical randomized studies on the effect of ILI showed a weight loss of more than 5% in selected patients, which could be partly sustained for several years. The ILI reduced risk factors without improving cardiovascular morbidity and mortality. The expensive clinical ILI had to be translated into an accessible and affordable primary care version. With this translation the effectiveness of the ILI has disappeared. With the current ILI, the weight loss is less than 5% and the health advantages are limited. It is foreseeable that the dismal results of the ILI will not generate enthusiasm among potential participants. The impact of ILI on the obesity epidemic will be very limited. Prevention will provide the way to go.

Long-term Emergency Department Visits and Readmissions After Laparoscopic Roux-en-Y Gastric Bypass: a Systematic Review.

PURPOSE: There is considerable evidence on short-term outcomes after laparoscopic Roux-en-Y gastric bypass (LRYGB), but data on long-term outcome is scarce, especially on postoperative emergency department (ED) visits and readmissions. We aim to systematically review evidence on the incidence, indications, and risk factors of ED visits and readmissions beyond 30 days after LRYGB. MATERIALS AND METHODS: A systematic search in PubMed, Scopus, Embase.com , Cochrane Library, and PsycINFO was performed. All studies reporting ED visits and readmissions > 30 days after LRYGB, with ≥ 50 patients, were included. PRISMA statement was used and the Newcastle-Ottawa Scale for quality assessment. RESULTS: Twenty articles were included. Six studies reported on ED visits (n = 2818) and 19 on readmissions (n = 276,543). The rate of patients with an ED visit within 90 days after surgery ranged from 3.9 to 32.6%. ED visits at 1, 2, and 3 years occurred in 25.6%, 30.0%, and 31.1% of patients. Readmissions within 90 days and at 1-year follow-up ranged from 4.1 to 20.5% and 4.75 to 16.6%, respectively. Readmission was 29% at 2 years and 23.9% at 4.2 years of follow-up. The most common reason for ED visits and readmissions was abdominal pain. CONCLUSION: Emergency department visits and readmissions have been reported in up to almost one in three patients on the long-term after LRYGB. Both are mainly indicated for abdominal pain. The report on indications and risk factors is very concise. A better understanding of ED visits and readmissions after LRYGB is warranted to improve long-term care, in particular for patients with abdominal pains.

[Preferably a gastric sleeve operation]. / Liever een 'gastric sleeve'-operatie.

One third of patients undergoing a gastric bypass operation will experience chronic abdominal symptoms. Diagnosis and treatment of this abdominal pain is a difficult task. The biggest problem is the ruling out of one of the possible causes of abdominal pain, such as internal herniation. Current diagnostic methods have generally not been successful in diagnosing internal herniation, and - more importantly - have not been able to rule out this diagnosis either. This leads to a high number of visits by these patients to the emergency department and outpatient clinic. Patients with pre-existing abdominal pain, or those who use analgesia preoperatively should preferably be treated by means of a gastric sleeve operation, instead of an operation involving anastomosis, such as a gastric bypass procedure.

[Tilting at WIP windmills in the OR: laminar flow might be harmful]. / Vechten tegen de WIP-windmolens op de OK.

The World Health Organization has published a new guideline for the prevention of surgical site infection (SSI), according to which laminar airflow systems should not be used to reduce the risk of SSI in the OR. The Dutch Health Care Inspectorate has, on the other hand, published a directive demanding laminar airflow in most operation rooms in Dutch hospitals. This directive is based on an evidence-based report from the Dutch Working Group on Infection Prevention (WIP). Since these guidelines are contradictory, the evidence presented in the WHO report as well as in the WIP report is evaluated in this article. The conclusion is that the WIP report used the available literature selectively, resulting in a favourable but false advantage for the laminar airflow system. The directive on laminar airflow should therefore be withdrawn and the WHO guideline should be implemented in Dutch hospitals.

Pharmacological evaluation of experimental isolated liver perfusion and hepatic artery infusion with 5-fluorouracil.

The intention of this study was to estimate the pharmacological advantage of a clinically applicable method of isolated liver perfusion (ILP) over hepatic artery infusion (HAI) administering various doses of 5-fluorouracil (FUra). FUra concentrations were measured using high-performance liquid chromatography in liver tissue (pigs and rats), hepatic tumor tissue (rats), and in the systemic circulation (pigs) following ILP and HAI. Forty-two pigs and 36 rats were subjected to either ILP or HAI with 20, 40 or 80 mg of FUra/kg of body weight. ILP resulted in significantly increased FUra concentrations in the liver as compared with the results with HAI in rats and pigs. Median areas under the concentration-time curve in liver tissue were 122.7 mumol.g-1.min and 59.9 mumol.g-1.min (40-mg/kg dose-group) and 236.3 mumol.g-1.min and 45.1 mumol.g-1.min (80 mg/kg) for ILP and HAI, respectively in pigs (both P less than 0.05). Systemic plasma areas under the curve were significantly lower for ILP as compared with HAI in 40- and 80-mg/kg dose-groups with 2.2 mumol.ml-1.min and 9.2 mumol.ml-1.min (40 mg/kg; P less than 0.01) and 6.8 mumol.ml-1.min and 43.2 mumol.ml-1.min (80 mg/kg; P less than 0.01) for ILP- and HAI-treated pigs, respectively. In hepatic tumor tissue a dose-dependent increase of mean FUra concentration was found for ILP-treated rats (P less than 0.05). No significant differences were observed in median FUra concentrations in tumor tissue between ILP- and HAI-treated rats (0.66 mumol.g-1 and 0.63 mumol.g-1 for ILP- and HAI-treated groups with 80 mg/kg; P greater than 0.05). The mean FUra concentration tumor/liver ratio was 0.26. In order to clarify the metabolic fate of high-dose FUra, five rats were subjected to HAI with 150 mg of FUra/kg, and hepatic tumor extracts excised at t = 0 min, t = 5 min, and t = 15 min after infusion were analyzed using 19F nuclear magnetic resonance. Catabolite alpha-fluoro-beta-alanine appeared rapidly at t = 5 min and t = 15 min in liver tissue. Significant amounts of the presumed active nucleotides were not detected in tumor tissue. We conclude that ILP is a means to improve selectivity of administration of antitumor agents to the liver, as compared with HAI. The pharmacological advantage of ILP over HAI administering equivalent doses of FUra was not demonstrated in tumor tissue, because of a large differential between liver tissue extraction and tumor tissue extraction of FUra, which was influenced by the mode of administration.

Relationships between type 2 diabetes remission after gastric bypass and different weight loss metrics: arguments against excess weight loss in metabolic surgery.

BACKGROUND: Percentage excess weight loss (%EWL) outcome of bariatric surgery is distorted by deviations in baseline body mass index (BMI). It has been reported that this can lead to false conclusions, most likely because bariatric weight loss in fact is baseline-BMI independent. OBJECTIVES: If the metabolic effect of bariatric surgery is baseline-BMI independent as well, could %EWL also lead to false conclusions on metabolic surgery? SETTING: Bariatric Center of Excellence, general hospital, Netherlands. METHODS: Retrospective analysis of 1-year outcome of all consecutive primary gastric bypass patients with type 2 diabetes (T2DM). Metabolic outcome (glycated hemoglobin [HbA1c], T2DM medication) was compared with bariatric outcome (weight loss) using 3 different metrics: %EWL, the most popular weight loss metric among bariatric surgeons; percentage (total) weight loss (%WL), most commonly used by nonsurgical professionals; and percentage alterable weight loss (%AWL), the only metric rendering weight loss outcome independent of baseline BMI. Metabolic success (HbA1c≤6.0%, T2DM remission) was compared with different definitions of bariatric success (≥50 %EWL, BMI<35 kg/m(2), %AWL percentiles; Mann-Whitney test; P< .05). RESULTS: Until May 2014, 2001 patients underwent primary laparoscopic Roux-en-Y gastric bypass (LRYGB), of whom 449 had T2DM with baseline BMI 43.3 kg/m(2), mean 1.6 number of T2DM medication and HbA1c 7.5%. At 1 year 95% follow-up, with BMI 30.5 kg/m(2), 52.1% T2DM remission, 86.9% HbA1c<7.0%, and 63.6% without T2DM medication. No significant differences in T2DM outcome and weight loss were found with different baseline BMI, except for %EWL (P<.001). Weight loss was significantly better with better T2DM outcome, but for %EWL contradictory relationships were found in baseline-BMI subgroups. T2DM outcome was not less successful for patients with<50 %EWL. CONCLUSION: In T2DM patients, weight loss after gastric bypass does not depend on BMI, HbA1c, or T2DM medication at baseline. The popular %EWL metric and the 50 %EWL success criterion are problematic in comparing bariatric and metabolic outcome of gastric bypass surgery. They should be abandoned. The %WL metric is the best and most commonly used alternative, whereas %AWL is ideal for selected logistics in bariatric research. Weight loss percentiles are best suited for defining bariatric success in metabolic surgery.

Laparoscopic adjustable gastric banding versus open vertical banded gastroplasty: a prospective randomized trial.

BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) and open vertical banded gastroplasty (VBG) are treatment modalities for morbid obesity. However, few prospective randomized clinical trials (RCT) have been performed to compare both operations. METHODS: 100 patients (50 per group) were included in the study. Postoperative outcomes included hospital length of stay (LOS), complications, percent excess weight loss (%EWL), BMI and reduction in total comorbidities. Follow-up in all patients was 2 years. RESULTS: LOS was significantly shorter in the LAGB group. 3 LAGB were converted to open (1 to gastric bypass). Directly after VBG, 3 patients needed relaparotomies due to leakage, of which one (2%) died. After 2 years, 100% follow-up was achieved. BMI and %EWL were significantly decreased in both groups but significantly more in the VBG group compared to the LAGB group (31.0 kg/m2 and 70.1% vs 34.6 and 54.9% respectively). Co-morbidities significantly decreased in both groups in time. 2 years after LAGB, 20 patients needed reoperation for pouch dilation/slippage (n=12), band leakage (n=2), band erosion (n=2) and access-port problems (n=4). In the VBG group, 18 patients needed revisional surgery due to staple-line disruption (n=15), narrow outlet (n=2) or insufficient weight loss (n=1). Furthermore, 8 VBG patients developed an incisional hernia. CONCLUSION: This RCT demonstrates that, despite the initial better weight loss in the VBG group, based on complication rates and clinical outcome, LAGB is preferred. It had a shorter LOS and less postoperative morbidity.

Internal biliary drainage, parenteral nutrition, and variation in the total parenteral nutrition feeding solutions: influence on the healing of colon anastomosis in jaundiced rats.

The influence of preoperative internal biliary drainage and various types of total parenteral nutrition (TPN) on the healing of a colon anastomosis in 50 jaundiced rats was investigated. Jaundice was induced by division and ligation of the common bile duct. After 5 days a colon anastomosis was made. Ten days thereafter the bursting pressure of the anastomosis was measured as an assessment of wound healing. Bursting pressures were significantly lower in jaundiced rats compared with a sham-operated nonjaundiced group. Preoperative internal biliary drainage significantly improved bursting pressure (p less than 0.001) as did preoperative TPN (p less than 0.001). In the second part of the study the influence of four different feeding solutions on the healing of a colon anastomosis was tested. Solutions with and without 20% fat emulsion and a solution with branched-chain amino acids were tested as well as glucose only. No significant differences were observed among these four groups on the parameters tested.

Validating the alterable weight loss (AWL) metric with 2-year weight loss outcome of 500 patients after gastric bypass.

BACKGROUND: Percentage alterable weight loss (AWL) is the only known weight loss metric independent of the initial body mass index (BMI), a unique feature ideal for use in weight loss research. AWL was not yet validated. The aim of the study is to validate the AWL metric and to confirm advantages over the excess weight loss (EWL) metric. METHODS: AWL is tested with 2-year weight loss results of all primary laparoscopic Roux-en-Y gastric bypass patients operated in our hospital. Nadir results of patients with higher and lower initial BMI are compared (Mann-Whitney; p < 0.05) using outcome metrics BMI, percentage weight loss (WL), EWL, and AWL, for the whole group, for each gender, and for <40 and ≥40 years separately. RESULTS: Five-hundred patients (401 female) out of 508 (98.4 %) had 2-year follow-up. Of all four metrics, only AWL rendered results not significantly influenced by initial BMI. The AWL outcome is initial BMI independent for both genders and age-groups. Results also confirm that women and younger patients had significantly higher AWL outcome. CONCLUSION: The recently developed AWL metric, defined as 100% × (initialBMI - BMI) / (initialBMI - 13), is now validated. In contrast to the well-known outcome metrics BMI, EWL, and WL, the AWL metric is independent of the initial BMI. It should replace the misleading EWL metric for comparing weight loss results in bariatric research and for expressing the effectiveness of bariatric procedures. This effectiveness does not act on the total body mass, or on the excess part, but on the alterable part, defined as BMI minus 13 kg/m(2) for all adult patients, female, male, young, and old.

Attitudes towards detection and management of hepatic metastases in the Western world.

In order to obtain insight in attitudes towards detection and management of hepatic metastases of colorectal origin, a questionnaire was sent to hospitals in 13 Western countries. Response rate was 98.0% (n = 284). In almost all hospitals (98%) some method of follow-up was employed. Carcino-embryonic antigen (CEA) determinations were performed in 84% of all hospitals: most frequently in Germany and the U.S.A., but only in 50% of the British hospitals. Hepatic resection for liver metastases was performed in 95% of all hospitals. Resectability criteria varied considerably among the countries. In the majority of German and American hospitals multiple hepatic metastases were considered resectable (including bilobar disease in 58% of German hospitals). In the majority of British and Dutch hospitals only solitary metastases were considered resectable, or liver resections were not performed at all. The mean reported number of liver resections annually per hospital, reflecting these attitudes, was 11.2 and 7.2 for German and American hospitals, and 2.1 and 1.8 for British and Dutch hospitals respectively. When irresectable hepatic metastases were diagnosed, some form of chemotherapy was applied in 74% of hospitals. Hepatic artery infusion of chemotherapeutics was performed most frequently. The mean reported number of medically treated patients annually per hospital was 34 for Germany, 18 for the U.S.A., and 12 and 9 for Great Britain and the Netherlands respectively. Adjuvant chemotherapy was performed after liver resection in 30% of all hospitals, most frequently in German and American hospitals. Considerable disparity was observed in attitudes towards detection and in management of hepatic metastases among Western countries. On the basis of the reported 1421 liver resections and 3590 medically treated patients (annually) it is concluded that selection of the best detection and treatment policies is obviously hampered by insufficient clinical data and inconclusive evidence of purported optimal approach. To determine the optimal policy useful information can only be provided by inclusion of patients in prospective randomized trials.