Stéfane Lebel

Large maternal weight loss from obesity surgery prevents transmission of obesity to children who were followed for 2 to 18 years.

OBJECTIVE. Our aim was to compare the prevalence of obesity in 172 children who were aged 2 to 18 years and born to 113 obese mothers (BMI: 31 ± 9 kg/m2) with substantial weight loss after biliopancreatic bypass surgery with 45 same-age siblings who were born before maternal surgery (mothers’ BMI: 48 ± 8 kg/m2) and with current population standards. METHODS. In this case series, with >88% follow-up in a tertiary referral center, crosssectional office chart and telephone data on childhood and adolescent weights were transformed to z scores. RESULTS. After maternal surgery, the prevalence of obesity in the offspring decreased by 52% and severe obesity by 45.1%, with no increase in the prevalence of underweight. The z score reduction in obesity was gender specific, with boys reducing from 1.4 ± 1.3 before to 0.57 ± 1.7 after maternal surgery, corrected for birth order. The difference was not significant in girls (0.8 ± 1.3 vs 0.8 ± 1.2). Among children of both genders who were aged 6 to 18 years of age and born after maternal surgery, the prevalence of overweight was reduced to population levels. CONCLUSIONS. Contrary to outcomes after intrauterine under- and overnutrition, the prevalence of overweight and obesity in children of mothers with large voluntary postsurgical weight loss was similar to that in the general population, with no increase in underweight. The results demonstrate the importance of potentially modifiable epigenetic factors in the cause of obesity.

MALABSORPTIVE OBESITY SURGERY

Biliopancreatic diversion is the only valuable surgical approach for changing intestinal absorption. It is efficient in producing appropriate permanent weight loss and has a considerable psychological advantage because it does not impose abnormal food restriction. It not only decreases caloric absorption, but it also directly improves insulin and lipid metabolism. The ideal technique for the construction of BPD is not yet established, but our current preference is for the duodenal switch type. BPD must be seen as a means to change an intolerable and untreatable disease to a tolerable and treatable one, with substantial improvement in quality of life.

Does bone change after biliopancreatic diversion

This prospective study evaluated bone changes after biliopancreatic diversion (BPD) consisting of a distal gastrectomy, a 250 cm alimentary channel, and a 50 cm common channel. Thirty-three consecutive patients had clinical, biochemical, and bone mineral density analysis before surgery and 4 and 10 years after surgery. Iliac crest bone biopsies and special tests including parathyroid hormone (PTH), 25-hydroxyvitamin D (25-OH-D), 1,25-dihydroxyvitamin D (1,25-OH2-D), bone-specific alkaline phosphatase (BAP), and osteocalcin were obtained at surgery and 4 years postoperatively. Over the years, with close metabolic surveillance, additional calcium and vitamin D were given as indicated. After BPD, serum levels of calcium and vitamin D were decreased and serum levels of PTH, BAP, and osteocalcin were increased. Bone turnover and mineralization were both increased. Mean osteoid volume (P < 0.0007) and bone formation rate in relation to bone volume (P < 0.02) were increased. Static measures of bone were altered as follows: cortical thickness decreased (P < 0.01) and trabecular bone volume increased (P < 0.01). Ten years after surgery, overall bone mineral density was unchanged at the hip and was decreased by 4% at the lumbar spine. Overall fracture risk, based on the Z score, was unchanged. Preoperative factors predicting bone loss included menopause, smoking, and preexisting osteopenia. An elevated level of 1,25-OH2-D was also found to be a predictor of future bone loss (r = 0.40; P < 0.002). After surgery, a greater increase in bone markers and bone turnover was associated with an increased risk of bone loss. Although elevated osteocalcin levels were associated with overall bone loss (r = 0.52; P < 0.002), lower albumin levels were associated only with bone loss at hip level (r = 0.44; P < 0.02), whereas lower calcium levels were associated only with the loss at the lumbar spine (r = 0.39; P < 0.02). Ten years after surgery, bone loss at the hip continued to depend on albumin levels (r = 0.37; P < 0.03). We concluded that bone was relatively tolerant to the metabolic changes due to BPD. Provided that there is close surveillance for metabolic disturbances, the use of appropriate supplements, and the avoidance of malnutrition, the beneficial effects of surgery far outweigh the risk of postoperative bone disease.

Omental and subcutaneous adipose tissue steroid levels in obese men.

We examined plasma and fat tissue sex steroid levels in a sample of 28 men aged 24.8-62.2 years (average BMI value of 46.3 +/- 12.7 kg/m(2)). Abdominal adipose tissue biopsies were obtained during general or obesity surgery. Omental and subcutaneous adipose tissue steroid levels were measured by gas chromatography and chemical ionization mass spectrometry after appropriate extraction procedures. BMI and waist circumference were negatively correlated with plasma testosterone (r = -0.49 and -0.50, respectively, p < 0.01) and dihydrotestosterone (r = -0.58 and -0.56, respectively, p < 0.01), and positively associated with estrone levels (r = 0.64 and 0.62, respectively, p < 0.001). Regional differences in adipose tissue steroid levels were observed for dihydrotestosterone (p < 0.005), androstenedione (p < 0.0001) and dehydroepiandrosterone levels (p < 0.05), which were all significantly more concentrated in omental versus subcutaneous fat. Positive significant associations were found between circulating level of a steroid and its concentration in omental and subcutaneous adipose tissue, for estrone (r = 0.72 and 0.57, respectively, p < 0.01), testosterone (r = 0.66 and 0.58, respectively, p < 0.01) and dihydrotestosterone (r = 0.58 and 0.45, respectively, p < 0.05). Positive correlations were observed between plasma dehydroepiandrosterone-sulfate and omental (r = 0.56, p < 0.01) as well as subcutaneous adipose tissue dehydroepiandrosterone level (r = 0.38, p = 0.05). Positive significant associations were found between omental adipocyte responsiveness to positive lipolytic stimuli (isoproterenol, dibutyryl cyclic AMP and forskolin) and plasma or omental fat tissue androgen levels. In conclusion, although plasma androgen or estrogen levels are strong correlates of adipose tissue steroid content both in the omental and subcutaneous fat depots, regional differences may be observed. Androgen concentration differences in omental versus subcutaneous adipose tissue suggest a depot-specific impact of these hormones on adipocyte function and metabolism.

Duodenal switch improved standard biliopancreatic diversion: a retrospective study.

BACKGROUND This was a retrospective study, performed 10 years after surgery, to compare the results between biliopancreatic diversion (BPD) with distal gastrectomy (DG) versus BPD with duodenal switch (DS). METHODS Complete follow-up data were available for 96% of patients, allowing a comparison of weight loss, revision, side effects, and complications at 10 years. RESULTS After BPD-DS, weight loss was 25% greater than after BPD-DG (46.8 +/- 21.7 kg versus 37.5 +/- 22 kg, respectively; P <.0001). The need for revision decreased from 18.5% to 2.7% (P <.0001), and the prevalence of vomiting during the previous month was 50% less (23.7-50.6%, P <.0001) after BPD-DS compared with after BPD-DG. Late complications were the same for both procedures. Blood analysis showed that, after BPD-DS, the levels of calcium, iron, and hemoglobin were significantly greater and the parathyroid hormone level was lower than after BPD-DG (71.3 +/- 44.2 versus 103.0 +/- 64.0 ng/L, respectively; P <.0001). CONCLUSION The DS greatly improved the BPD, as it was initially proposed. The use of the DS increased weight loss, decreased the need for revision, resulted in fewer side effects, and improved the absorption of nutrients.

Perioperative complications in a consecutive series of 1000 duodenal switches

BACKGROUND In the past 10 years, most bariatric surgeries have seen an important reduction in the early complication rate, partly associated with the development of the laparoscopic approach. Our objective was to assess the current early complication rate associated with biliopancreatic diversion with duodenal switch (BPD-DS) since the introduction of a laparoscopic approach in our institution, a university-affiliated tertiary care center. METHODS A consecutive series of 1000 patients who had undergone BPD-DS from November 2006 to January 2010 was surveyed. The primary endpoint was the mortality rate. The secondary endpoints were the major 30-day complication rate and hospital stay >10 days. The data are reported as a mean ± SD, comparing the laparoscopic (n = 228) and open (n = 772) groups. RESULTS The mean age of the patients was 43 ± 10 years (40 ± 10 years in the laparoscopy group versus 44 ± 10 years in the open group, P < .01). The preoperative body mass index was 51 ± 8 kg/m(2) (47 ± 7 laparoscopy versus 52 ± 8 kg/m(2) open, P < .01). The conversion rate in the laparoscopy group was 2.6%. There was 1 postoperative death (.1%) from a pulmonary embolism in the laparoscopy group. The mean hospital stay was shorter after laparoscopic surgery (6 ± 6 d versus 7 ± 9 d, P = .01), and a hospital stay >10 days was more frequent in the open group (4.4% versus 7%, P = .04). Major complications occurred in 7% of the patients, with no significant differences between the 2 groups (7% versus 7.4%, P = .1). No differences were found in the overall leak or intra-abdominal abscess rate (3.5% versus 4%, P = .1); however, gastric leaks were more frequent after open surgery (0% versus 2%, P = .02). During a mean 2-year follow-up, 1 additional death occurred from myocardial infarction, 2 years after open BPD-DS. CONCLUSION The early and late mortality rate of BPD-DS is low and comparable to that of other bariatric surgeries.

Change in fracture risk and fracture pattern after bariatric surgery: nested case-control study

Objective To investigate whether bariatric surgery increases the risk of fracture. Design Retrospective nested case-control study. Setting Patients who underwent bariatric surgery in the province of Quebec, Canada, between 2001 and 2014, selected using healthcare administrative databases. Participants 12 676 patients who underwent bariatric surgery, age and sex matched with 38 028 obese and 126 760 non-obese controls. Main outcome measures Incidence and sites of fracture in patients who had undergone bariatric surgery compared with obese and non-obese controls. Fracture risk was also compared before and after surgery (index date) within each group and by type of surgery from 2006 to 2014. Multivariate conditional Poisson regression models were adjusted for fracture history, number of comorbidities, sociomaterial deprivation, and area of residence. Results Before surgery, patients undergoing bariatric surgery (9169 (72.3%) women; mean age 42 (SD 11) years) were more likely to fracture (1326; 10.5%) than were obese (3065; 8.1%) or non-obese (8329; 6.6%) controls. A mean of 4.4 years after surgery, bariatric patients were more susceptible to fracture (514; 4.1%) than were obese (1013; 2.7%) and non-obese (3008; 2.4%) controls. Postoperative adjusted fracture risk was higher in the bariatric group than in the obese (relative risk 1.38, 95% confidence interval 1.23 to 1.55) and non-obese (1.44, 1.29 to 1.59) groups. Before surgery, the risk of distal lower limb fracture was higher, upper limb fracture risk was lower, and risk of clinical spine, hip, femur, or pelvic fractures was similar in the bariatric and obese groups compared with the non-obese group. After surgery, risk of distal lower limb fracture decreased (relative risk 0.66, 0.56 to 0.78), whereas risk of upper limb (1.64, 1.40 to 1.93), clinical spine (1.78, 1.08 to 2.93), pelvic, hip, or femur (2.52, 1.78 to 3.59) fractures increased. The increase in risk of fracture reached significance only for biliopancreatic diversion. Conclusions Patients undergoing bariatric surgery were more likely to have fractures than were obese or non-obese controls, and this risk remained higher after surgery. Fracture risk was site specific, changing from a pattern associated with obesity to a pattern typical of osteoporosis after surgery. Only biliopancreatic diversion was clearly associated with fracture risk; however, results for Roux-en-Y gastric bypass and sleeve gastrectomy remain inconclusive. Fracture risk assessment and management should be part of bariatric care.

Biliopancreatic diversion (doudenal switch procedure).

The physiological principle underlying biliopancreatic diversion (BPD) is attractive. It decreases food absorption and particularly that of fat. It preserves normal eating habits and is compatible with a good quality of life. Because weight loss is not a function of an imposed aversion to eating, it is more appealing to patients. Data are accumulating showing that BPD can permanently cure morbid obesity in a majority of patients and is remarkably well tolerated. While long-term systemic side-effects from decreased absorption continue to raise concerns, available results have already shown that, within 20 years, metabolic disturbances are well tolerated while weight loss and quality of life are maintained. Vitamin and mineral replacement therapy and periodic monitoring are essential. The original procedure described by Scopinaro with subsequent modifications will be presented, focusing on the duodeno-ileal switch procedure.

Transoral endoscopic restrictive implant system: a new endoscopic technique for the treatment of obesity

Morbid obesity remains a major health problem through-out western countries, and surgery is the only long-termoption for this disease and its associated pathologic features.New techniques have been developed in the past few yearsto further decrease the complication rate of obesity surgery,including single-incision laparoscopic surgery [1], natural-orifice transluminal endoscopic surgery [2], and endoscopicsurgery [3]. Endoscopic surgery, by avoiding any injury tothe abdominal wall, theoretically represents an ideal ap-proach to obesity surgery.The aim of the present study was to describe a newendoscopic technique for the treatment of obesity called thetransoral endoscopic restrictive implant system (BaroSense,Redwood City, CA).

Characterization of Dedifferentiating Human Mature Adipocytes from the Visceral and Subcutaneous Fat Compartments: Fibroblast-Activation Protein Alpha and Dipeptidyl Peptidase 4 as Major Components of Matrix Remodeling

Mature adipocytes can reverse their phenotype to become fibroblast-like cells. This is achieved by ceiling culture and the resulting cells, called dedifferentiated fat (DFAT) cells, are multipotent. Beyond the potential value of these cells for regenerative medicine, the dedifferentiation process itself raises many questions about cellular plasticity and the pathways implicated in cell behavior. This work has been performed with the objective of obtaining new information on adipocyte dedifferentiation, especially pertaining to new targets that may be involved in cellular fate changes. To do so, omental and subcutaneous mature adipocytes sampled from severely obese subjects have been dedifferentiated by ceiling culture. An experimental design with various time points along the dedifferentiation process has been utilized to better understand this process. Cell size, gene and protein expression as well as cytokine secretion were investigated. Il-6, IL-8, SerpinE1 and VEGF secretion were increased during dedifferentiation, whereas MIF-1 secretion was transiently increased. A marked decrease in expression of mature adipocyte transcripts (PPARγ2, C/EBPα, LPL and Adiponectin) was detected early in the process. In addition, some matrix remodeling transcripts (FAP, DPP4, MMP1 and TGFβ1) were rapidly and strongly up-regulated. FAP and DPP4 proteins were simultaneously induced in dedifferentiating mature adipocytes supporting a potential role for these enzymes in adipose tissue remodeling and cell plasticity.