Tissue-specific inflammation and insulin sensitivity in subjects with obesity.

Obesity is associated with low-grade inflammation and insulin resistance (IR). The contribution of adipose tissue (AT) and hepatic inflammation to IR remains unclear. We conducted a study across three cohorts to investigate this relationship. The first cohort consists of six women with normal weight and twenty with obesity. In women with obesity, we found an upregulation of inflammatory markers in subcutaneous and visceral adipose tissue, isolated AT macrophages, and the liver, but no linear correlation with tissue-specific insulin sensitivity. In the second cohort, we studied 24 women with obesity in the upper vs lower insulin sensitivity quartile. We demonstrated that several omental and mesenteric AT inflammatory genes and T cell-related pathways are upregulated in IR, independent of BMI. The third cohort consists of 23 women and 18 men with obesity, studied before and one year after bariatric surgery. Weight loss following surgery was associated with downregulation of multiple immune pathways in subcutaneous AT and skeletal muscle, alongside notable metabolic improvements. Our results show that obesity is characterised by systemic and tissue-specific inflammation. Subjects with obesity and IR show a more pronounced inflammation phenotype, independent of BMI. Bariatric surgery-induced weight loss is associated with reduced inflammation and improved metabolic health.

The BAPRAS screening tool for reimbursement in a postbariatric population.

INTRODUCTION: Reimbursement of body-contouring surgery (BCS) is a worldwide problem: there is no objective instrument to decide which postbariatric patients should qualify for reimbursement. The British Association of Plastic, Reconstructive and Aesthetic Surgeons (BAPRAS) has developed a screening tool for this purpose. In this study, we used a modified version of this screening tool in a postbariatric population and describe which patients would qualify for reimbursement using this tool. METHODS: In this cross-sectional study postbariatric patients were asked to fill in an online questionnaire based on the BAPRAS screening tool with questions regarding complaints of overhanging skin and medical history. Weight loss data were extracted from a prospective database. The BODY-Q was added to assess patient-reported outcomes. RESULTS: Patients who wanted to undergo BCS (n = 90) had higher screening tool scores and lower BODY-Q scores compared to patients who did not want BCS (n = 24). In total, 25 patients (26%) qualified for reimbursement, these patients had higher weight loss (33.5% versus 29.2%, p = 0.008), lower BMI (27.3 kg/m2 versus 30.4 kg/m2, p = 0.014) and more medical (4.0 versus 2.0, p = 0.004) and psychological complaints (88% versus 61%, p = 0.009). There was a significant, negative correlation between the screening tool scores and almost all BODY-Q scales. CONCLUSIONS: Patients with a desire for BCS have more complaints of excess skin, which negatively impacts their well-being. With the modified BAPRAS screening tool, patients with the best weight (loss) and most medical and psychological complaints of excess skin qualified for referral and reimbursement of BCS.

Clinical follow-up on weight loss, glycemic control, and safety aspects of 24 months of duodenal-jejunal bypass liner implantation.

BACKGROUND: The duodenal-jejunal bypass liner (DJBL) is an endoscopic device designed to induce weight loss and improve glycemic control. The liner is licensed for a maximum implant duration of 12 months. It might be hypothesized that extension of the dwelling time results in added value. The goals of our study were to determine weight change, change in glycemic control, and safety in patients with an intended 24 months of DJBL dwelling time. METHODS: Patients were initially selected for a 12-month implantation period. When no physical complaints or adverse events (AEs) occurred, motivated patients who responded well were selected for extension of dwelling time to 24 months. Patients underwent a control endoscopy 12 months after implantation and visited the out-patient clinic every 3 months up to explantation. Patients agreed to remove the DJBL when complaints or AEs occurred that could not be treated conservatively. RESULTS: Implantation was extended in 44 patients, and 24 (55%) patients completed the full 24 months. Twenty patients required early removal due to AEs. During dwelling time, body weight decreased significantly (15.9 kg; TBWL 14.6%). HbA1c decreased non-significantly (4.9 mmol/mol). The number of insulin users and daily dose of insulin both decreased significantly. At 24 months after removal, glycemic control had worsened, while body weight was still significantly lower compared to baseline. In total, 68% of the patients experienced at least one AE. Two patients developed a hepatic abscess. CONCLUSIONS: DJBL treatment results in significant weight loss and improves glycemic control during implantation. The largest beneficial effects occur during the first 9-12 months after implantation. Extension of dwelling time to 24 months results only in stabilization of body weight and glycemic control. After explantation, weight improvements are maintained, but glycemic control worsens. As the cumulative risk of AEs increases with time, a maximal dwelling time of 12 months is advisable.

Genetic Obesity and Bariatric Surgery Outcome in 1014 Patients with Morbid Obesity.

BACKGROUND: Mutations in the leptin-melanocortin pathway genes are known to cause monogenic obesity. The prevalence of these gene mutations and their effect on weight loss response after bariatric surgery are still largely unknown. OBJECTIVE: To determine the prevalence of genetic obesity in a large bariatric cohort and evaluate their response to bariatric surgery. METHODS: Mutation analysis of 52 obesity-associated genes. Patient inclusion criteria were a BMI > 50 kg/m2, an indication for revisional surgery or an early onset of obesity (< 10 years of age). RESULTS: A total of 1014 patients were included, of whom 30 (3%) were diagnosed with genetic obesity, caused by pathogenic heterozygous mutations in either MC4R, POMC, PCSK1, SIM1, or PTEN. The percentage total body weight loss (%TBWL) after Roux-en-Y gastric bypass (RYGB) surgery was not significantly different for patients with a mutation in MC4R, POMC, and PCSK1 compared with patients lacking a molecular diagnosis. Of the confirmed genetic obesity cases, only patients with MC4R mutations receiving a sleeve gastrectomy (SG) showed significantly lower %TBWL compared with patients lacking a molecular diagnosis, during 2 years of follow-up. CONCLUSIONS: In this cohort of morbid obese bariatric patients, an estimated prevalence of monogenic obesity of 3% is reported. Among these patients, the clinical effects of heterozygous mutations in POMC and PCSK1 do not interfere with the effectiveness of most commonly performed bariatric procedures within the first 2 years of follow-up. Patients with MC4R mutations achieved superior weight loss after primary RYGB compared with SG.

Weight Loss, Remission of Comorbidities, and Quality of Life After Bariatric Surgery in Young Adult Patients.

INTRODUCTION: One of the current criteria for bariatric surgery is to be of an age between 18 and 65 years. In all the available literature, there is a lack of studies focusing on the results of bariatric surgery in younger patient. This could be of great interest because the weight loss response can be altered by differences in metabolism or compliance rate. In recent years, a high amount of patients between 18 and 25 years of age have undergone bariatric surgery in our center, and it is our aim to evaluate the weight loss results in this youngest patient group. METHODS: All preoperative and perioperative data from patients aged 18-25 and 35-55 years (control group) were collected retrospectively. Bariatric procedures took place between 2011 and 2014. Follow-up data were gathered prospectively by collecting (laboratory) measurements and questionnaires. RESULTS: In total, 103 young adults (mean age 22.5) were matched to 103 adult control patients (mean age 42.6) on BMI and date of surgery. Of the young adults' group, 75 patients underwent a Roux-en-Y gastric bypass (RYGB) compared with 80 patients in the control group. Three years after RYGB, mean %total body weight loss (%TBWL) was 34 (± 9) and 30.3 (± 9) (p = 0.03), respectively. CONCLUSION: Bariatric surgery is effective in young adults, and results after RYGB are even better compared with age groups in which bariatric surgery is most often performed. The high remission rate of comorbidities shows the importance of effective treatment options at a young age and preventing damaging effects in the long term.

Altered neural inhibition responses to food cues after Roux-en-Y Gastric Bypass.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) surgery is a highly effective weight-loss intervention that often reduces preference and intake of high-energy foods. Research into the neural mechanisms behind this shift has mainly focused on reward processing of food cues. However, the ability to successfully control food intake and thereby weight-loss also depends on inhibitory control capacity. We investigated whether RYGB leads to alterations in neural inhibitory control in response to food cues. METHODS: A food-specific go/no-go task with pictures of high-energy (desserts) and low-energy foods (vegetables), was used to assess neural inhibition responses before and after RYGB with functional magnetic resonance imaging. Data from 18 morbidly obese patients (15 females; age 41 ±â€¯11 years; BMI 42 ±â€¯4 kg/m2 before; BMI 36 ±â€¯4 kg/m2 after) were analysed. Pre- and post-RYGB BOLD fMRI responses were compared for response inhibition towards high- and low-energy foods. Participants were tested in a satiated state. RESULTS: Response inhibition to high-energy foods was associated with increased activation of the right lateral prefrontal cortex (PFC), right medial PFC, dorsolateral PFC, right middle cingulate cortex and the right inferior frontal operculum (involved in inhibitory control), after compared to before surgery. Response inhibition to low-energy foods elicited diminished post- compared to pre-surgery responses in the left superior temporal pole, right parahippocampal gyrus and right hypothalamus (involved in metabolic control). CONCLUSION: Neural changes indicate improved response inhibition towards high-energy food cues, altered influence of metabolic control during response inhibition towards low-energy food cues and a more positive attitude to both high-energy and low-energy food after RYGB. Alterations in neural circuits involved in inhibitory control, satiety signalling and reward processing may contribute to effective weight-loss after RYGB.

The Effect of Obesity on Anti-Xa Concentrations in Bariatric Patients.

BACKGROUND: Morbidly obese patients are at increased risk to develop venous thromboembolism (VTE), especially after bariatric surgery. Adequate postoperative thrombosis prophylaxis is of utmost importance. It is assumed that morbidly obese patients need higher doses of low molecular weight heparin (LMWH) compared to normal-weight patients; however, current guidelines based on relative efficacy in obese populations are lacking. OBJECTIVES: First, we will evaluate the relationship between body weight descriptors and anti-Xa activity prospectively. Second, we will determine the dose-linearity of LMWH in morbidly obese patients. SETTING: This study was performed in a general hospital specialized in bariatric surgery. METHODS: Patients were scheduled for a Roux-en-Y gastric bypass with a total bodyweight (TBW) of ≥ 140 kg. Patients (n = 50, 64% female) received a daily postoperative dose of 5700 IU of nadroparin for 4 weeks. Anti-Xa activity was determined 4 h after the last nadroparin administration. To determine the dose linearity, anti-Xa was determined following a preoperative dose of 2850 IU nadroparin in another 50 patients (52%). RESULTS: TBW of the complete group was 148.5 ± 12.6 kg. Mean anti-Xa activity following 5700 IU nadroparin was 0.19 ± 0.07 IU/mL. Of all patients, 32% had anti-Xa levels below the prophylactic range. Anti-Xa activity inversely correlated with TBW (correlation coefficient - 0.410) and lean body weight (LBW; correlation coefficient - 0.447); 67% of patients with a LBW ≥ 80 kg had insufficient anti-Xa activity concentrations. No VTE events occurred. CONCLUSIONS: In morbidly obese patients, a postoperative dose of 5700 IU of nadroparin resulted in subprophylactic exposure in a significant proportion of patients. Especially in patients with LBW ≥ 80 kg, a higher dose may potentially be required to reach adequate prophylactic anti-Xa levels.

Is reimplantation of the duodenal-jejunal bypass liner feasible?

BACKGROUND: The endoscopic ally implanted DJBL is a 60-cm impermeable fluoropolymer device, which prevents food from making contact with the proximal intestine. It was designed to induce weight loss and treat type 2 diabetes mellitus (T2DM). OBJECTIVES: To evaluate the feasibility, safety, and effectiveness of duodenal-jejunal bypass liner (DJBL) reimplantation. SETTING: Prospective, observational study was conducted at the department of surgery and gastroenterology of the Rijnstate hospital, Arnhem, the Netherlands, between 2009 and 2011. METHODS: Five obese patients with T2DM with body mass index (BMI) = Mass (kg) / height (m(2)), ranging from 30-35 kg/m(2) who completed the follow-up after their first implant and underwent removal of the DJBL after 6 months, were selected for reimplantation after an additional 18 months of follow-up. Weight loss, BMI, and HbA1 c were analyzed before and twelve months after reimplantation. RESULTS: In all 5 patients, the DJBL was implanted and explanted without any complications. Also the reimplantation and reexplantation occurred without any complications. Median weight decreased significantly from 105 kg to 95 kg, and BMI decreased from 33 to 29. The glycated hemoglobin (HbA1 c) level decreased from 8.4% to 7.3% by the first implantation but it wasn't significant. CONCLUSIONS: Reimplantation of DJBL is feasible, deemed safe, and showed additional weight loss.

Long-term effects of laparoscopic Roux-en-Y gastric bypass on diabetes mellitus, hypertension and dyslipidaemia in morbidly obese patients.

BACKGROUND: Severely obese patients have an increased risk for developing metabolic complications such as type 2 diabetes mellitus (T2DM), dyslipidaemia (DL) and hypertension (HT). The aim of the present study is to research the effect of a primary laparoscopic Roux-en-Y gastric bypass (LRYGB) on T2DM, HT and DL in the long-term. METHODS: Fifty-two out of 89 (58 %) adult severely obese patients with T2DM who had received a LRYGB between January 2000 and December 2008 were evaluated. Primary outcome of evaluation was remission of T2DM according to the definition of 2009 consensus statement. Complete remission was defined as achievement fasting plasma glucose (FPG) of <5.6 mmol/l (<100.8 mg/dL) and HbA1c <42 mmol/mol (<6.0 %)) without glucose-lowering medication for at least 1 year. Partial remission was defined as a FPG of 5.6-6.9 mmol/l (100.8-124.2 mg/dL) and HbA1c 42-48 mmol/mol (6.0-6.5 %), without glucose-lowering medication for at least 1 year. Remission of T2DM was considered if the patient met the criteria for complete or partial remission. Secondary outcomes were remission of HT, DL and changes in medication use. RESULTS: Patients had a mean age of 47.5 ± 9.6 years, body mass index of 46.6 ± 6.4 kg/m(2) and a mean duration of T2DM of 6.1 ± 5.4 years at the time of surgery. The mean post-operative follow-up period was 6.9 ± 2.3 years. At the end of the follow-up, mean weight loss was 60 ± 24 % excess weight loss (EWL) and 26 ± 10 % total body weight loss (TBWL). Mean HbA1c level had significantly decreased from 64.8 ± 19.7 mmol/mol to 46.4 ± 12.9 mmol/l (p < 0.0001). Overall medication use was reduced from 85 % to 37 % of the patients (p < 0.0001), while the number of insulin users was reduced from 40 % to 6 % (p < 0.0001). Nineteen percent of the patients had a relapse of T2DM during follow-up. Pre-operative HbA1ac level (odds ratio 0.911, p = 0.020) and duration of T2DM (odds ratio 0.637, p = 0.010) were independent risk factors for failed remission of T2DM. The number of patients with HT was significantly reduced from 73 % to 54 % (p = 0.042), and number of patients with DL was non-significantly decreased from 71 % to 54 % (p = 0.068). CONCLUSIONS: The laparoscopic RYGB operation results in a sustained EWL of 60 % (26 % TBWL) with 52 % long-term remission of T2DM. However, 19 % of the patients had a relapse of their T2DM. Furthermore, HT and DL improved markedly.

Long-term results after laparoscopic adjustable gastric banding: a mean fourteen year follow-up study.

BACKGROUND: For over a decade, the laparoscopic adjustable gastric band (LAGB) was 1 of the most performed bariatric procedures in Europe. This study is a retrospective analysis with prospectively collected data of the experience in 1 specialized Dutch center with the adjustable gastric band over 14 years. METHODS: Between 1995 and 2003, 201 patients underwent an LAGB for morbid obesity in our hospital. Data on preoperative clinical characteristic, postoperative outcome and weight loss patterns, and co-morbidities for up to 18 years are presented and evaluated using the Bariatric Analysis and Reporting Outcome System (BAROS). RESULTS: Average follow-up was 13.6 (± 2.0) years (163 mo) and 99% of patients with complete follow-up. Two thirds of patients reached an excess weight loss (EWL)>50% at some point after LAGB placement. However, due to insufficient weight loss or complications in 53% of patients, the LAGB had to be removed or converted to a Roux-en-Y gastric bypass. Additionally, half of the remaining patients had disappointing results according to the BAROS score. In total, less than one quarter (22%) of patients had a functioning band with a good result after the follow-up period. Although initially the number of patients experiencing co-morbidities was reduced, most of them returned and a large number of patients developed new co-morbidities. Complications, other than weight regain, were numerous as 47% of patients experienced at least 1. In total, 204 reoperations were performed in 137 (68%) patients. Furthermore, patients who were lost to follow-up did almost twice as bad in terms of EWL compared to patients who had regular follow-up. CONCLUSION: Morbid obesity is a chronic disease that can be resolved with bariatric surgery. One of the treatment options is the LAGB, which in the short term shows good results in terms of EWL and co-morbidity reduction. In the long term, however, EWL and co-morbidity reduction are disappointing, and the LAGB does not seem to live up to expectations. Besides the decrease in EWL over time, the number of reoperations required is alarming. In total, less than a quarter of patients still had a functioning band after a mean 14 years of follow-up.

The impact of surgical complications as a main risk factor for venous thromboembolism: a multicenter study.

BACKGROUND: Studies suggest that postoperative complications are a risk factor for venous thromboembolism (VTE) after bariatric surgery. Knowledge of factors associated with a higher risk of VTE after bariatric surgery may be essential to select patients who may benefit from either prolonged or intensified thrombosis prophylaxis. The aim of this study is to determine the relationship between postoperative complications and VTE after bariatric surgery and other classical risk factors. METHODS: A retrospective multicenter case-control study was performed in patients who had bariatric surgery between January 2008 and September 2011. VTE until 6 months after surgery was registered, and patients were contacted to ascertain the results. For every case of VTE after surgery, 6 control patients were selected who were matched for gender, age, participating center and type of surgery. Risk factors for VTE before and after surgery and postoperative complications were registered. RESULTS: A total of 2,064 surgeries were included. In 12 patients, VTE occurred within 6 months after bariatric surgery (incidence 0.58 %, 95 % confidence interval (CI) = 0.25-0.93). There was a strong association of complications after surgery (cases 91.7 %, controls 15.3 %, odds ratio (OR) 61.0; 95 % CI = 7.1-521.3) or intensive care admission (cases 50.0 %, controls 11.1 %, OR = 8.0; 95 % CI = 2.1-30.8) with VTE. The majority of postoperative complications were anastomotic leak, abdominal abscess, and infection. We could not detect an association between classical thrombosis risk factors and postoperative VTE. CONCLUSIONS: The incidence of VTE is low after bariatric surgery using thrombosis prophylaxis. However, there is a strong association between postoperative complications and VTE. These patients may benefit from more intensive thrombosis prophylaxis.

Hepatic and peripheral insulin sensitivity do not improve 2 weeks after bariatric surgery.

OBJECTIVE: Bariatric surgery has rapid metabolic effects on glucose metabolism before the occurrence of clinically significant weight loss. This suggests an acute effect of the surgery itself, e.g., resulting from bypassing the nutrient flow from the proximal gastrointestinal tract. Rapid effects of Roux-en-Y gastric bypass surgery (RYGB) on glucose metabolism were defined. DESIGN AND METHODS: Glucose metabolism and total triglyceride hydrolysis in the basal state and during a hyperinsulinemic euglycemic clamp using stable isotopes 2 weeks were studied before and after RYGB. RESULTS: Eighteen pre-menopausal women scheduled for RYGB were included. 2 weeks after RYGB median weight loss was 7.8 kg. Basal insulin and glucose levels decreased after surgery. Endogenous glucose production (EGP) was lower after surgery. In addition, insulin levels were lower during the clamp after surgery, suggesting enhanced clearance. Hepatic and peripheral insulin sensitivity did not change. Free fatty acid (FFA) levels increased after surgery both in the basal state and during the first step of the clamp. Total triglyceride hydrolysis did not change in the basal state and tended to be higher during hyperinsulinemia. CONCLUSIONS: Within 2 weeks, RYGB reduces basal EGP as well as insulin and glucose levels without an acute beneficial effect on hepatic or peripheral insulin sensitivity. The latter may be explained by higher rates of lipolysis and exposure to FFA induced by the hypocaloric state.

Preoperative fasting plasma C-peptide level may help to predict diabetes outcome after gastric bypass surgery.

BACKGROUND: To evaluate whether preoperative measurement of fasting plasma C-peptide levels is useful to predict diabetes outcome after Roux-en-Y gastric bypass (RYGB) surgery. MATERIALS AND METHODS: Diabetes outcome after RYGB was evaluated in 126 obese patients: 41 non-diabetic controls (NDC), 29 with impaired glucose tolerance (IGT) and 56 had type 2 diabetes mellitus (T2DM). Body weight, fasting plasma glucose, fasting C-peptide levels, and HbA1c were measured at baseline and 3.6 ± 0.16 years after GBS. Complete resolution of diabetes was defined as: fasting glucose <7.0 mmol/l, HbA1c <6.5 %, achieved without anti-diabetic medication. RESULTS: Patients with complete resolution of diabetes had a more recent diagnosis of T2DM, lower preoperative HbA1c levels and lower daily doses of metformin and insulin use. These parameters were related to postoperative HbA1c levels but they failed to mark the specific patients who had not reached complete resolution of T2DM. Fasting preoperative C-peptide levels had better predictive power: 90 % of T2DM patients with preoperative fasting C-peptide levels >1.0 nmol/l achieved a postoperative HbA1c <6.5 %, and 74 % achieved complete resolution of their diabetes. In contrast, none of the T2DM patients with a preoperative fasting C-peptide <1.0 nmol/l attained these goals. CONCLUSIONS: A preoperative fasting plasma C-peptide level <1.0 nmol/l in severely obese T2DM patients indicates partial ß-cell failure, and is associated with a markedly reduced chance of complete resolution of T2DM after RYGB. We therefore advocate measuring C-peptide levels in all diabetic patients up for bariatric surgery to improve the prediction of outcome.

Prevalence of Anemia and Related Deficiencies in the First Year following Laparoscopic Gastric Bypass for Morbid Obesity.

Background. Anemia associated with deficiencies in iron, folic acid, and vitamin B12 are very common after Laparoscopic Roux-en-Y Gastric Bypass (LRYGB) surgery for morbid obesity. This study was conducted to evaluate the prevalence of anemia after LRYGB. Patients and Methods. A total of 377 morbid obese patients were included in our study. All patients underwent a LRYGB. Hematologic parameters were obtained prior to and after surgery on standardized time intervals. Results. Anemia was present in 21 (P = 0.02) patients after surgery. Iron, folic acid, and vitamin B12 deficiencies were diagnosed in 66%, 15%, and 50% of patients, respectively. In 86% of patients, anemia was accompanied by one of these deficiencies. Conclusion. These results show that anemia and deficiencies for iron, folic acid deficiency, and vitamin B12 are very common within the first year after LRYGB. We advise a minimal daily intake of 65 mg of iron in male and 100 mg in female patients, 350 µg of vitamin B12, and 400 µg of folic acid. Patients undergoing LRYGB must be closely monitored for deficiencies pre- and postoperative and supplemented when deficiencies occur.

Semiquantitative assessment of bowel habits and its relation with calcium metabolism after gastric bypass surgery: a retrospective study.

Background. Calcium malabsorption after bariatric surgery may be harmful to skeletal health and demands for optimal skeletal management. Methods. 103 Patients were evaluated retrospectively at 12 months after surgery. The evaluation included a questionnaire about stool frequency and consistency and laboratory assessments. Results. 103 Patients, 27 males and 76 females, were included in the study. 83 Patients had an alimentary limb of 100 cm and 20 patients one of 150 cm. At 12 months after surgery, 77.7% reported changes of bowel habits, albumin adjusted calcium levels were normal in all but 2 patients, and PTH levels were increased in 35%. Correlations between semiquantified bowel scores (fecal scores) and data from the laboratory demonstrated increasing PTH values along with more frequent and softer/watery stools (RR 30.5, CI 6.2-149.2, P < .001). There was a trend for higher PTH levels in patients with an alimentary limb of 150 cm. Normal PTH levels were more frequently found in case of calcium and vitamin D3 use (RR 14.3, CI 3.6-56.5, P < .001). Conclusion. This study demonstrates interrelationships between semi-quantified fecal scores, PTH levels, and the compliance of taking calcium/vitamin D3 suppletion. However, prospective randomized studies are necessary to show causal relationships.

Access-port fixation on the left pectoral fascia in laparoscopic adjustable gastric banding.

Access-port (AP) complications after laparoscopic adjustable gastric banding (LAGB) are often seen but seldom reported in literature. AP complications requiring additional surgery is reported in 3.6% to 24% of LAGB patients (Susmallian et al. Obes. Surg, 4:128-131, 2003; Peterli et al. Obes. Surg., 12(6):851-856, 2002; Busetto et al. Obes. Surg., 12:83-92, 2002; Mittermair et al. Obes. Surg., 19:446-450, 2009; Holeczy et al. Obes. Surg., 9:453-455, 1999; Bueter et al. Arch. Surg., 393:199-205, 2008; Launay-Savary et al. Obes Surg, 18:1406-1410, 2008; Balsiger et al. J. Gastrointest. Surg., 11:1470-1477, 2007; Szold and Abu-Abeid Surg. Endosc., 16:230-233, 2002). We evaluated the effect of fixing the AP on the pectoral fascia using the Velocity™ Injection Port on complication and re-operation rate. From January 2005 till October 2007, 619 LAGB procedures were performed using the SAGB QuickClose™. All procedures were performed by three dedicated surgeons using the pars flaccida technique. APs were placed on the fascia of the pectoral muscle using an infra-mammary incision. The AP device was fixed on the fascia using the Velocity™ Injection Port and Applier. Data was obtained retrospectively and records of 619 consecutive patients were reviewed for access-port complications. Sixty-eight AP complications were observed. Complications could be divided in four categories. Discomfort was reported in 30 patients, seven needing additional surgery. Infection contributed to 11 patients needing surgical removal of the device. Fourteen Patients with superficial infection were treated conservatively. Nine patients had inaccessible APs. Ultrasound-guided access was required in three patients. The remainder needed surgical relocation of the AP. Leakage of the tube was observed in four patients all of which needed revisional surgery. Our experience shows that fixation of the AP on the left pectoral fascia using the Velocity™ leads to a readily accessible AP with good anaesthetic and aesthetic results. In our series, 68 (11%) complications were recorded, of which 28 (4.5%) needed additional surgery.

Constitutional DNA copy number changes in ICSI children.

BACKGROUND: Over the last three decades, technological developments facilitating assisted reproductive techniques (ART) have revolutionized the treatment of subfertile couples, including men suffering from severe oligospermia or azoospermia. In parallel with the advent of these technologies, there is a great concern about the biological safety of ART. This concern is supported by the clinical observation that the frequency of congenital malformations is slightly elevated among ART-conceived children. METHODS: In this explorative study, we have used tiling-resolution BAC array-mediated comparative genomic hybridization to investigate the incidence of de novo genomic copy number changes in a group of 12 ICSI children, compared with a control group of 30 naturally conceived children. RESULTS: In 6 of the 12 ICSI children, we found 10 apparently de novo 'same direction genomic copy number changes' [i.e. simultaneous copy number gain (or loss) with respect to both biological parents], notably losses. In statistically significant contrast, similar observations were encountered only six times in the control group in 5 of the 30 children. However, our study group was small, so a larger group is needed to confirm these findings. CONCLUSIONS: Loci at which we found de novo alterations are known from the human genome database to be prone to large DNA segment copy number changes. As discussed, various molecular mechanisms, including the consequences of delayed male meiotic synapsis and replication fork stalling at early embryonic cell cycles, might trigger these copy number changes.

CNTNAP2 gene dosage variation is associated with schizophrenia and epilepsy.

A homozygous mutation of the CNTNAP2 gene has been associated with a syndrome of focal epilepsy, mental retardation, language regression and other neuropsychiatric problems in children of the Old Order Amish community. Here we report genomic rearrangements resulting in haploinsufficiency of the CNTNAP2 gene in association with epilepsy and schizophrenia. Genomic deletions of varying sizes affecting the CNTNAP2 gene were identified in three non-related Caucasian patients. In contrast, we did not observe any dosage variation for this gene in 512 healthy controls. Moreover, this genomic region has not been identified as showing large-scale copy number variation. Our data thus confirm an association of CNTNAP2 to epilepsy outside the Old Order Amish population and suggest that dosage alteration of this gene may lead to a complex phenotype of schizophrenia, epilepsy and cognitive impairment.

[Gastric reduction in morbidly obese adults in the Netherlands]. / Maagverkleining bij volwassenen met morbide obesitas in Nederland.

Obesity results in several health problems, the most important of these being diabetes mellitus type 2. In patients with morbid obesity (BMI > or = 35 kg/m(2) and comorbidity or BMI > or = 40 kg/m(2)) in particular, prevention or treatment of health problems resulting from the obesity is only possible with considerable and lasting weight loss. Gastric reduction surgery with the adjustable gastric band has been shown to be safe and effective. This is also true for the more invasive techniques such as the gastric bypass and the biliopancreatic diversion. Surgical treatment is the only treatment that can induce substantial and lasting weight loss (> 50% of the excess weight, on average) in this patient group in the long run. Although the availability of surgical treatment is as yet inadequate in the Netherlands, it has recently improved considerably. Reimbursement of the treatment is however still an obscure issue and the reimbursement of the follow-up is uncertain. Possibly, the current experiments with independent treatment centers will be able to put an end to this uncertainty.