Publications by authors named "Jean-Luc Bouillot"

90 Publications

Maintenance of a Gastric Pacemaker in the Excluded Stomach During a Roux-en-Y Gastric Bypass Procedure in a Patient with Obesity, Type 1 Diabetes and Refractory Gastroparesis.

Obes Surg 2021 Dec 6;31(12):5497-5499. Epub 2021 Oct 6.

Centre Hospitalier Universitaire Ambroise Paré, Service d'Endocrinologie Diabétologie et Nutrition, Assistance Publique-Hôpitaux de Paris, 9 avenue Charles De Gaulle, 92100, Boulogne Billancourt, France.

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http://dx.doi.org/10.1007/s11695-021-05726-xDOI Listing
December 2021

Endoscopic Management of Bariatric Surgery Complications According to a Standardized Algorithm.

Obes Surg 2021 10 23;31(10):4327-4337. Epub 2021 Jul 23.

Unité d'Endoscopie Interventionnelle, Hôpital Privé des Peupliers, Ramsay Générale de Santé, 8 Place de l'Abbé G. Hénocque, 75013, Paris, France.

Background And Aims: Endoscopy is effective in management of bariatric surgery (BS) adverse events (AEs) but a comprehensive evaluation of long-term results is lacking. Our aim is to assess the effectiveness of a standardized algorithm for the treatment of BS-AE.

Patients And Methods: We retrospectively analyzed 1020 consecutive patients treated in our center from 2012 to 2020, collecting data on demographics, type of BS, complications, and endoscopic treatment. Clinical success (CS) was evaluated considering referral delay, healing time, surgery, and complications type. Logistic regression was performed to identify variables of CS.

Results: In the study period, we treated 339 fistulae (33.2%), 324 leaks (31.8%), 198 post-sleeve gastrectomy twist/stenosis (19.4%), 95 post-RYGB stenosis (9.3 %), 37 collections (3.6%), 15 LAGB migrations (1.5%), 7 weight regains (0.7%), and 2 hemorrhages (0.2%). Main endoscopic treatments were as follows: pigtail-stent positioning under endoscopic view for both leaks (CS 86.1%) and fistulas (CS 77.2%), or under EUS-guidance for collections (CS 88.2%); dilations and/or stent positioning for sleeve twist/stenosis (CS 80.6%) and bypass stenosis (CS 81.5%). After a median (IQR) follow-up of 18.5 months (4.29-38.68), complications rate was 1.9%. We found a 1% increased risk of redo-surgery every 10 days of delay to the first endoscopic treatment. Endoscopically treated patients had a more frequent regular diet compared to re-operated patients.

Conclusions: Endoscopic treatment of BS-AEs following a standardized algorithm is safe and effective. Early endoscopic treatment is associated with an increased CS rate.
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http://dx.doi.org/10.1007/s11695-021-05577-6DOI Listing
October 2021

Endoscopic internal drainage for the management of leak, fistula, and collection after sleeve gastrectomy: our experience in 617 consecutive patients.

Surg Obes Relat Dis 2021 Aug 23;17(8):1432-1439. Epub 2021 Mar 23.

Service de chirurgie digestive et obésité, Clinique Bizet, Paris, France.

Background: Endoscopy plays a pivotal role in the management of adverse events (AE) following bariatric surgery. Leaks, fistulae, and post-operative collection after sleeve gastrectomy (SG) may occur in up to 10% of cases.

Objectives: To evaluate the efficacy and safety of endoscopic internal drainage (EID) for the management of leak, fistula, and collection following SG.

Setting: Retrospective, observational, single center study on patients referred from several bariatric surgery departments to an endoscopic referral center.

Methods: EID was used as first-line treatment for the management of leaks, fistulae, and collections. Leaks and fistulae were treated with double pigtail stent (DPS) deployment in order to guarantee internal drainage and second intention cavity obliteration. Collections were treated with endoscropic ultrasound (EUS)-guided deployment of DPS or lumen apposing metal stents.

Results: A total of 617 patients (83.3% female; mean age, 43.1 yr) were enrolled in the study for leak (n = 300, 48.6%), fistula (n = 285, 46.2%), and collection (n = 32, 5.2%). Median follow-up was 19.5 months. Overall clinical success was 84.7% whereas 15.3% of cases required revisional surgery after EID failure. Clinical success according to type of AE was 89.5%, 78.5%, and 90% for leak, fistula, and collection, respectively. A total of 10 of 547 (1.8%) presented a recurrence during follow-up. A total of 28 (4.5%) AE related to the endoscopic treatment occurred. At univariate logistic regression predictors of failure were: fistula (OR 2.012), combined endoscopic approach (OR 2.319), need for emergency surgery (OR 1.755), and previous endoscopic treatment (OR 4.818).

Conclusion: Early EID for the management of leak, fistula, and post-operative collection after SG seems a safe and effective first-line approach with good long-term results.
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http://dx.doi.org/10.1016/j.soard.2021.03.013DOI Listing
August 2021

Weight Loss After Sleeve Gastrectomy: Does Type 2 Diabetes Status Impact Weight and Body Composition Trajectories?

Obes Surg 2021 03 4;31(3):1046-1054. Epub 2020 Nov 4.

Assistance Publique-Hôpitaux de Paris, Nutrition Department, Pitié-Salpêtrière Hospital, CRNH Ile de France, Sorbonne Université, Batiment IE3M, 6th floor, 46-83 Boulevard de l'Hôpital, 75013, Paris, France.

Introduction/ Purpose: Sleeve gastrectomy (SG), the most frequently performed bariatric procedure, induces marked weight-loss, but with high inter-individual variability. Since type 2 diabetes (T2D) negatively impacts weight-loss outcomes after Roux-en-Y gastric bypass (RYGB), we herein aimed to evaluate whether and how T2D status may influence weight-loss and body composition changes in individuals with or without T2D after SG.

Material And Methods: We retrospectively included individuals with obesity operated from SG and prospectively followed at our center: 373 patients including 152 with T2D (40%). All subjects' clinical characteristics were collected before and during 4 years of follow-up post-SG. Linear mixed models were applied to analyze weight-loss trajectories post-surgery.

Results: Compared to individuals with obesity but no T2D, those with T2D before SG displayed lower weight-loss at 1 year (21 vs. 27% from baseline, p < 10). This difference was accentuated in patients with poorer glucose control (HbA1c > 7%) at baseline. Furthermore, patients with T2D underwent less favorable body composition changes at 1-year post-SG compared to individuals without T2D (% fat mass reduction: 28 vs. 37%, p < 10 respectively).

Conclusion: When undergoing SG, subjects with obesity and T2D who have poor pre-operative glycemic control display reduced weight-loss and less improvement in body composition compared to patients with obesity but without T2D. This result suggests that glycemic control prior to surgery is important to take into account for the outcome of bariatric surgery.
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http://dx.doi.org/10.1007/s11695-020-05075-1DOI Listing
March 2021

Right Colectomy with Absorbable Mesh Repair as a Salvage Solution for the Management of Giant Incisional Hernia with Loss of Domain: Results of a Bicentric Study.

World J Surg 2020 06;44(6):1762-1770

Department of Digestive and Bariatric Surgery, Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France.

Background: Incisional hernia (IH) may occur in 20% of patients after laparotomy. The hernia sac volume may be of significance, with reintegration of visceral contents potentially leading to repair failure or abdominal compartment syndrome. The present study aimed to evaluate a two-step surgical strategy comprising right colectomy for hernia reduction with synchronous absorbable mesh repair followed by definitive non-absorbable mesh repair in recurrence.

Methods: Patients operated between 2012 and 2017 at two university centers were retrospectively included. Volumetric evaluation of the IH was performed by CT imaging.

Results: Eleven patients were included. The mean BMI was 43 kg/m (23-52 kg/m). Progressive preoperative pneumoperitoneum was performed in 82% of patients, with complications in 22%. The mean volumetric ratio of the volume of the hernia to the volume of the abdominal cavity was 70% (48-100%). The first parietal repair was performed using an synthetic absorbable mesh (36%), a biologic mesh (27%), or a slowly absorbable mesh (36%). No patients died as a result of the procedure. Seven (64%) patients developed grade III-IV complications, including one case of an anastomotic fistula. Recurrence occurred in eight (73%) patients after the first repair. Of these, four (50%) patients were reoperated using a non-absorbable mesh, leading to solid repair in 75% of cases. After 27 ± 18 months of follow-up, the residual IH rate was 46%.

Conclusions: Right colectomy for volume reduction in IH with loss of domain potentially represents an appropriate salvage option, supporting bowel reintegration and temporary hernia repair with absorbable material.
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http://dx.doi.org/10.1007/s00268-020-05395-4DOI Listing
June 2020

Diagnostic and Therapeutic Management of Post-Gastric Bypass Chronic Diarrhea: a Systematic Review.

Obes Surg 2020 Mar;30(3):1102-1111

AP-HP, Department of Nutrition, Centre spécialisé de l'Obesité Hôpital Européen Georges Pompidou, Paris, France.

There is a lack of recommendation regarding exploration and treatment of chronic diarrhea following gastric bypass, while it is a common side effect of this surgery. The electronic databases MEDLINE and EMBASE were searched until July 2018. Of the 553 articles identified, 35 articles were included. Intestinal bacterial overgrowth and pancreatic exocrine insufficiency are the main etiologies of diarrhea following gastric bypass. The diagnostic approach must begin by eliminating infectious causes of diarrhea. Exocrine pancreatic insufficiency can be diagnosed with fecal fat quantification or fecal elastase 1 level evaluation. A positive lactulose breath test confirms suspicion of small intestine bacterial overgrowth. In conclusion, we propose sequential exploration and treatment of the possible etiologies of diarrhea depending on clinical symptoms.
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http://dx.doi.org/10.1007/s11695-019-04253-0DOI Listing
March 2020

Laparoscopic Revision of Bariatric Surgeries in Two Patients with Severe Resistant Hypocalcemia After Endocrine Cervical Surgery.

Obes Surg 2020 04;30(4):1616-1620

Department of Endocrinology, Diabetology and Nutrition, Ambroise Paré University Hospital, 9 Av Charles de Gaulle, 92100, Boulogne Billancourt, France.

Severe hypocalcemia complicating cervical endocrine surgery in patients with gastric bypass can constitute a major concern. When usual therapies fail to maintain calcemia within the normal range without secondary adverse events, reversal of the bariatric surgery should be considered. We herein report the outcomes of laparoscopic revision of bariatric surgeries in two patients suffering from severe resistant hypocalcemia following cervical surgery, requiring in one case recombinant PTH administration and, in the other, daily intravenous calcium injections. The Roux-en-Y gastric bypass was switched to sleeve gastrectomy in the first patient, and in the second patient, the biliopancreatic diversion with duodenal switch was revised, to restore the upper and distal parts of the alimentary tract. Rapid improvement of hypocalcemia was observed in both cases.
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http://dx.doi.org/10.1007/s11695-019-04132-8DOI Listing
April 2020

abundance is lower in severe obesity, but its increased level after bariatric surgery is not associated with metabolic health improvement.

Am J Physiol Endocrinol Metab 2019 09 2;317(3):E446-E459. Epub 2019 Jul 2.

Sorbonne Université, Institut National de la Santé et de la Recherche Médicale, Nutrition & Obesity-Systemic Approaches Research Group (NutriOmics), Institute of Cardiometabolism and Nutrition, Paris, France.

The gut bacterial species is associated with a healthier clinical profile. The purpose of this study was to determine the association between and glucose homeostasis in patients undergoing bariatric surgery (BS): gastric banding (GB) or Roux-en-Y gastric bypass (RYGB). This nonrandomized prospective study included 65 women with severe obesity. Longitudinal analysis included subjects for whom data were available at follow-up [1, 3, and 12 mo; GB ( = 10) or RYGB ( = 11)]. Glucose homeostasis markers were measured under fasting conditions (glucose, insulin, and HbA1c) or during an oral glucose tolerance test. Fecal microbiota was analyzed using shotgun metagenomics, and relative abundance was assessed with 16S rRNA quantitative PCR. relative abundance was significantly lower in severe obesity [mean body mass index, 45.7 kg/m (SD 5.4)] than in moderate obesity [33.2 kg/m (SD 3.8)] but not associated with glucose homeostasis markers. A significant increase in relative abundance after RYGB was not correlated with metabolic improvement. Baseline abundance was correlated with bacterial gene richness and was highest in the high-richness Ruminococcaceae enterotype. increased in relative abundance after BS in patients with low baseline . abundance, especially those with a type 2 enterotype classification. Although decreased in severe obesity, relative abundance of was not associated with glucose homeostasis before or after BS. A certain level of abundance might be required to observe a beneficial link to health. The severity of obesity and gut dysbiosis may partly explain the discrepancy with previous findings in less obese populations.
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http://dx.doi.org/10.1152/ajpendo.00140.2019DOI Listing
September 2019

CYP450 activities before and after Roux-en-Y gastric bypass: correlation with their intestinal and liver content.

Surg Obes Relat Dis 2019 Aug 20;15(8):1299-1310. Epub 2019 May 20.

Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Biologie du Médicament et Toxicologie, Paris, France; Inserm, UMR-S 1144 Université Paris Descartes-Paris Diderot, Variabilité de réponse aux psychotropes, Paris, France.

Background: Several anatomic and physiologic changes occur after Roux-en-Y gastric bypass (RYGB) and its associated weight loss. At present, no single unified model can predict changes in drug metabolism associated with either RYGB surgery or weight loss.

Objective: The aim of this longitudinal human study was to measure the activity of the 5 most important Cytochrome P450 (CYP) involved in drug metabolism in patients with obesity before and after RYGB. Jejunal and liver biopsies obtained during bariatric surgery were used to measure CYP amount, and correlation between jejunal and hepatic content was estimated.

Setting: French university hospital.

Methods: Eleven volunteers with a mean body mass index of 44.1 (39.4-50.0) kg/m participated in the study. CYP1 A2, CYP2 C9, CYP2 C19, CYP2 D6, and CYP3 A4/A5 activities were measured with a cocktail approach before surgery (visit 1), 5 to 8 weeks after surgery (visit 2), and 25 to 30 weeks after surgery (visit 3).

Results: CYP3 A4/A5 and CYP2 C9 metabolic ratios were transitorily and significantly increased immediately after surgery (visit 2 versus 1). RYGB procedure does not lead to significant change in CYP activity 25 to 30 weeks after surgery (visit 3 versus 1). Samples obtained during surgery showed significant correlation between intestinal and liver contents of CYP2 C9 and CYP3 A4/A5. Except for liver CYP1 A2 content, CYP metabolic activities were not correlated to their intestinal or liver contents.

Conclusions: This study showed that RYGB does not lead to a significant change in CYP activity 25 to 30 weeks after surgery. However, CYP3 A4/A5 and CYP2 C9 activities were transitorily and significantly increased in the immediate postoperative context (<1 mo), representing a situation at risk of reduced drug exposure for several drugs that have a narrow therapeutic window. In addition, considering high interindividual variability in liver contents and activity of CYP3 A4 and CYP2 C9, patients receiving drugs highly metabolized by these 2 CYPs should be closely monitored in the immediate postoperative period.
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http://dx.doi.org/10.1016/j.soard.2019.05.019DOI Listing
August 2019

Changes in Body Composition, Comorbidities, and Nutritional Status Associated with Lower Weight Loss After Bariatric Surgery in Older Subjects.

Obes Surg 2019 11;29(11):3589-3595

Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié-Salpêtrière Hospital, Nutrition Department, Sorbonne University, Institute of Cardiometabolism and Nutrition (ICAN), 47-83 boulevard de l'Hôpital, 75013, Paris, France.

Background: To provide greater insight into bariatric surgery outcomes in aging patients, we compared changes in body weight, body composition, obesity-related comorbidities, and nutritional status between older and younger subjects.

Methods: We analyzed data collected between January 2004 and December 2014 from our prospective bariatric cohort. Older patients (OP, ≥ 60 years at the time of surgery, n = 93; 66% Roux-en-Y gastric bypass, 34% sleeve gastrectomy) were compared with younger patients (YP, < 60 years, n = 186), matched 1:2 on sex, body mass index, diabetes, and surgical procedure. Body composition was assessed by dual-energy X-ray absorptiometry.

Results: Weight loss and excess weight loss at 12 months were lower in OP vs. YP (mean ± SD, 30.1 ± 10.1 vs. 34.1 ± 11.9 kg, 60.6 ± 21.2 vs. 66.8 ± 23.4%, respectively, p < 0.05 for both). Both lean body mass and fat mass loss were lower in OP vs. YP (8.4 ± 3.4 vs. 9.2 ± 9.0 kg, 19.4 ± 8.7 vs. 21.9 ± 9.1 kg, respectively, p < 0.05). The remission rate for type 2 diabetes was significantly lower in OP vs. YP (24 vs. 45%), as well as improvement in hypertension (14 vs. 46%), dyslipidemia (27 vs. 47%), and knee pain. There was no difference in micronutrient deficiencies between groups.

Conclusions: These data indicate that although bariatric surgery is not as effective for weight loss in older as in younger subjects, it is a safe option regarding a comprehensive set of nutritional variables which enables significant improvement in obesity-related outcomes.
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http://dx.doi.org/10.1007/s11695-019-04037-6DOI Listing
November 2019

Changes in total sperm count after gastric bypass and sleeve gastrectomy: the BARIASPERM prospective study.

Surg Obes Relat Dis 2019 08 25;15(8):1271-1279. Epub 2019 Apr 25.

Hôpital Européen Georges Pompidou, Service de Nutrition, Centre Spécialisé Obésité (CSO) Ile-de-France Sud, APHP, Université Paris Descartes, Paris, France; Centre d'Épidémiologie Clinique, Hôpital Hôtel-Dieu, Paris, France; Team METHODS, Centre of Research in Epidemiology and Statistics Sorbonne, Paris Cité-CRESS Inserm UMR1153, Paris, France; Université Paris Descartes, Paris, France.

Background: The massive weight loss induced by bariatric surgery is associated with major benefits, but the effect on semen variables is still uncertain.

Objectives: To explore semen modifications with gastric bypass and sleeve gastrectomy.

Setting: Five French University Hospitals.

Methods: Male candidates for bariatric surgery with no history of infertility were recruited in this controlled prospective study. Sperm characteristics were collected before surgery and then 6 months and up to 12 months after surgery.

Results: Forty-six adult men who underwent gastric bypass (n = 20) or sleeve gastrectomy (n = 26) were included. Total sperm count tended to be lower at 6 months and showed a significant decrease at 12 months in both surgery groups, at -69.5 million (-96.8 to -42.2 million; P = 0.0021). Total sperm count at 12 months relative to baseline was -41.4 million (P = .0391) after gastric bypass and -91.1 million (P = .0080) after sleeve gastrectomy. This was counterbalanced by an associated resolution of hypogonadism and decrease of DNA fragmentation in most patients with time after surgery.

Conclusion: Improvement in some semen variables after bariatric surgery observed in 3 previous studies is in contrast to the lower mean total sperm count found in this study at 1 year. The possible reversibility of this effect in the long term and the impact of surgery on fertility both remain unknown.
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http://dx.doi.org/10.1016/j.soard.2019.04.019DOI Listing
August 2019

Ventral hernia surgery in morbidly obese patients, immediate or after bariatric surgery preparation: Results of a case-matched study.

Surg Obes Relat Dis 2019 01 10;15(1):83-88. Epub 2018 Oct 10.

AP-HP, Department of Digestive, Oncologic and Metabolic Surgery, Ambroise Paré Hospital, Boulogne-Billancourt, France; Versailles St-Quentin-en-Yvelines/Paris Saclay University, UFR des Sciences de la Santé Simone Veil, Montigny-Le-Bretonneux, France.

Background: Obesity is a risk factor for the development of ventral hernia and increases the risk of recurrence and surgical site infection after hernia repair (HR).

Objectives: We tested the hypothesis that bariatric surgery (BS) before HR would decrease these risks in patients with morbid obesity.

Setting: University hospital, France.

Methods: We retrospectively compared 2 groups of patients with morbid obesity in a case-matched study; 1 underwent immediate HR surgery (control), and the other initially underwent BS and then HR after weight loss (case). Patients were individually matched at a 2:1 ratio according to defect size (<7 or ≥7 cm), obesity grade (<40 or ≥40 kg/m²), American Society of Anesthesiologists score, sex, smoker status, and presence of chronic obstructive pulmonary disease.

Results: From 2000 to 2017, 41 patients underwent BS, in association with herniorrhaphy in 14 cases (34%). Initial body mass index was higher in the BS group (46.7 ± 6.4 versus 42.4 ± 7.2, P < .0001) but had decreased by the time of HR (34.1 ± 6.5 versus 42.3 ± 7.2, P < .0001). Prosthetic HR was performed after 21.5 months (range, 7-87); however, 7 patients did not receive HR at this time due to insufficient weight loss. Postoperative morbidity was similar in the 2 groups. Hospital stay was shorter in the BS group (6.2 ± 2.6 versus 10.7 ± 9.3 d, P = .002). After a median follow-up of 4.6 ± 4.1 years, the recurrence rate was lower in the BS group (2/30, 6.7%) than in the control group (12/50, 24%; P = .048).

Conclusion: For morbidly obese patients with ventral hernia, BS before HR surgery can decrease recurrence without increasing morbidity.
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http://dx.doi.org/10.1016/j.soard.2018.09.490DOI Listing
January 2019

Resistance Training and Protein Supplementation Increase Strength After Bariatric Surgery: A Randomized Controlled Trial.

Obesity (Silver Spring) 2018 11;26(11):1709-1720

Department of Nutrition, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Sorbonne Université, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France.

Objective: Physical activity and dietary regimens to optimize health outcomes after bariatric surgery are not well known. This study aimed to determine whether resistance training with dietary protein supplementation is effective in maintaining body composition and physical fitness after obesity surgery.

Methods: Seventy-six women with obesity undergoing Roux-en-Y gastric bypass were randomly assigned at the time of surgery to receive either usual care (controls [CON], n = 22), usual care and additional (whey) protein intake (PRO, n = 31), or usual care, additional protein intake, and supervised strength training for 18 weeks (PRO+EX, n = 23). The primary outcome was pre- to 6-month postsurgery change in lean body mass (by dual-energy x-ray absorptiometry). Secondary outcomes included changes in muscle strength (by one-repetition maximum testing).

Results: Loss over time in lean body mass did not differ between groups (CON: mean,-8.8 kg; 95% CI: -10.1 to -7.5 kg; PRO: mean, -8.2 kg; 95% CI: -9.3 to -7.1 kg; PRO+EX: mean, -7.7 kg; 95% CI: -9.0 to -6.5 kg; P = 0.899). The increase in relative lower-limb muscle strength was higher in the PRO+EX group (+0.6 [0.3 to 0.8]) versus +0.1 (-0.1 to 0.4) and +0.2 (0.0 to 0.4) kg/kg body mass in CON and PRO groups, respectively (P = 0.021).

Conclusions: Loss in muscle strength observed after bariatric surgery can be overcome by resistance training with additional protein intake.
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http://dx.doi.org/10.1002/oby.22317DOI Listing
November 2018

Long-term Relapse of Type 2 Diabetes After Roux-en-Y Gastric Bypass: Prediction and Clinical Relevance.

Diabetes Care 2018 10 6;41(10):2086-2095. Epub 2018 Aug 6.

NutriOmics team, Sorbonne Université, INSERM, Paris, France

Objective: Roux-en-Y gastric bypass (RYGB) induces type 2 diabetes remission (DR) in 60% of patients at 1 year, yet long-term relapse occurs in half of these patients. Scoring methods to predict DR outcomes 1 year after surgery that include only baseline parameters cannot accurately predict 5-year DR (5y-DR). We aimed to develop a new score to better predict 5y-DR.

Research Design And Methods: We retrospectively included 175 RYGB patients with type 2 diabetes with 5-year follow-up. Using machine learning algorithms, we developed a scoring method, 5-year Advanced-Diabetes Remission (5y-Ad-DiaRem), predicting longer-term DR postsurgery by integrating medical history, bioclinical data, and antidiabetic treatments. The scoring method was based on odds ratios and variables significantly different between groups. This score was further validated in three independent RYGB cohorts from three European countries.

Results: Compared with 5y-DR patients, patients who had relapsed after 5 years exhibited more severe type 2 diabetes at baseline, lost significantly less weight during the 1st year after RYGB, and regained more weight afterward. The 5y-Ad-DiaRem includes baseline (diabetes duration, number of antidiabetic treatments, and HbA) and 1-year follow-up parameters (glycemia, number of antidiabetic treatments, remission status, 1st-year weight loss). The 5y-Ad-DiaRem was accurate (area under the receiver operating characteristic curve [AUROC], 90%; accuracy, 85%) at predicting 5y-DR, performed better than the Diabetes Remission score (DiaRem) and the Advanced-DiaRem (AUROC, 81% and 84%; accuracy, 79% and 78%, respectively), and correctly reclassified 13 of 39 patients misclassified with the DiaRem. The 5y-Ad-DiaRem robustness was confirmed in the independent cohorts.

Conclusions: The 5y-Ad-DiaRem accurately predicts 5y-DR and appears relevant to identify patients at risk for relapse. Using this score could help personalize patient care after the 1st year post-RYGB to maximize weight loss, limit weight regains, and prevent relapse.
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http://dx.doi.org/10.2337/dc18-0567DOI Listing
October 2018

Major microbiota dysbiosis in severe obesity: fate after bariatric surgery.

Gut 2019 01 13;68(1):70-82. Epub 2018 Jun 13.

Sorbonne Université, INSERM, NutriOmics Team, ICAN, Paris, France.

Objectives: Decreased gut microbial gene richness (MGR) and compositional changes are associated with adverse metabolism in overweight or moderate obesity, but lack characterisation in severe obesity. Bariatric surgery (BS) improves metabolism and inflammation in severe obesity and is associated with gut microbiota modifications. Here, we characterised severe obesity-associated dysbiosis (ie, MGR, microbiota composition and functional characteristics) and assessed whether BS would rescue these changes.

Design: Sixty-one severely obese subjects, candidates for adjustable gastric banding (AGB, n=20) or Roux-en-Y-gastric bypass (RYGB, n=41), were enrolled. Twenty-four subjects were followed at 1, 3 and 12 months post-BS. Gut microbiota and serum metabolome were analysed using shotgun metagenomics and liquid chromatography mass spectrometry (LC-MS). Confirmation groups were included.

Results: Low gene richness (LGC) was present in 75% of patients and correlated with increased trunk-fat mass and comorbidities (type 2 diabetes, hypertension and severity). Seventy-eight metagenomic species were altered with LGC, among which 50% were associated with adverse body composition and metabolic phenotypes. Nine serum metabolites (including , and ) and functional modules containing protein families involved in their metabolism were strongly associated with low MGR. BS increased MGR 1 year postsurgery, but most RYGB patients remained with low MGR 1 year post-BS, despite greater metabolic improvement than AGB patients.

Conclusions: We identified major gut microbiota alterations in severe obesity, which include decreased MGR and related functional pathways linked with metabolic deteriorations. The lack of full rescue post-BS calls for additional strategies to improve the gut microbiota ecosystem and microbiome-host interactions in severe obesity.

Trial Registration Number: NCT01454232.
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http://dx.doi.org/10.1136/gutjnl-2018-316103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7143256PMC
January 2019

Sleeve Gastrectomy in Morbidly Obese HIV Patients: Focus on Anti-retroviral Treatment Absorption After Surgery.

Obes Surg 2018 09;28(9):2886-2893

INSERM, UMRS, NutriOmicsTeam, Sorbonne Université, Paris, France.

Context: Anti-retroviral therapy (ART) dramatically reduced AIDS development, thus enabling patients to live as long as the general population. New challenges have emerged particularly cardiometabolic diseases and weight gain, with some HIV patients seeking bariatric surgery (BS). However, BS outcomes during HIV remain poorly described, with scarce data on ART pharmacokinetic post-BS.

Objective: Describing sleeve gastrectomy (SG) results in HIV patients in terms of ART pharmacokinetic, HIV control, weight loss, and metabolic outcomes.

Design, Setting, And Patients: Prospective study of HIV patients undergoing SG in a referral academic center, with at least 6 months follow-up.

Main Outcome Measure: Clinical and biological parameters, HIV medical history, and ART pharmacokinetics were gathered before and post-SG.

Results: Seventeen patients (mean BMI = 44.2 ± 5.7 kg m) and major obesity-related diseases (47% type-2 diabetes, 64% obstructive sleep apnea, 70% hypertension) underwent SG during a mean 2 years of follow-up. They displayed an average of 20% reduction of initial BMI and improved body composition, similarly to obese non-HIV patients. SG improved metabolic status. All patients had undetectable viral load before BS. Upon HIV follow-up, 12 patients had undetectable viral load with correct ART kinetic parameters (3 and 6 months); 4 displayed detectable viral load along with significant decrease in raltegravir and atazanavir treatment exposure, leading to ART change with subsequent undetectable viral load; and 1 had persistent detectable viral load despite ART change.

Conclusions: SG seems effective and safe in obese HIV patients. However, ART treatment should be monitored post-SG to control HIV infection. We suggest that some ART should be adapted before SG conjoints with infectious disease specialists.
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http://dx.doi.org/10.1007/s11695-018-3308-7DOI Listing
September 2018

Human catalase gene promoter haplotype and cardiometabolic improvement after bariatric surgery.

Gene 2018 May 27;656:17-21. Epub 2018 Feb 27.

INSERM, U1139, Faculty of Pharmacy, Paris Descartes University, Paris, France; Assistance Publique- Hôpitaux de Paris, Department of Automated Biological Diagnostic, Cochin Hospital, Paris, France. Electronic address:

Although its powerful impact on most co-morbidities has been widely demonstrated, the metabolic outcomes of bariatric surgery (BS) show a great heterogeneity among patients. Haplotypes of one of the major antioxidant enzyme, catalase (CAT), are associated with hypertension, dyslipidemia, and diabetes. The haplotype referred to as CAT1 includes homozygous carriers of CATH1 [-844G,-89A,-20T], whereas CAT2 haplotype includes heterozygous carriers (CATH1/CATH2) and CATH2 homozygous [-844A,-89T,-20C]. The aim of our study was to evaluate the impact of CAT1 and CAT2 haplotypes on traditional cardiovascular and metabolic markers one year after BS in a women population. The 294 women with a body mass index (BMI) >35 kg/m2 were followed-up for one year after BS, monitoring their anthropometric, metabolic and inflammatory parameters. CAT1 patients had significantly improved diastolic blood pressure (DBP) and Creactive protein (CRP) levels compared to CAT2 one year after BS. In untreated women at baseline, the change of CRP one year after BS was higher in CAT1 patients. In the population of women receiving at least one anti-lipidic, anti-hypertensive or anti-diabetic treatment at baseline, DBP and fat mass were lower one year after BS in CAT1 patients and the greater change of fat mass was associated with a higher change of adiponectin. The results highlight the beneficial impact of the CAT1 haplotype on traditional cardiovascular and metabolic parameters after BS. Our findings suggest that the CAT1 haplotype could be implicated in the level of metabolic and cardiovascular improvement after BS.
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http://dx.doi.org/10.1016/j.gene.2018.02.064DOI Listing
May 2018

Heat Shock Protein 60 in Obesity: Effect of Bariatric Surgery and its Relation to Inflammation and Cardiovascular Risk.

Obesity (Silver Spring) 2017 12 11;25(12):2108-2114. Epub 2017 Oct 11.

INSERM, U1166, team 6 Nutriomique, Université Pierre et Marie Curie-Paris 6, Paris, France.

Objective: Heat shock protein 60 (Hsp60) is an adipokine, and its serum concentrations are higher in patients with obesity compared to lean patients. This study aimed to analyze the effect of bariatric surgery on circulating concentrations of Hsp60 in morbid obesity and their correlation with inflammation and metabolic and cardiovascular risk.

Methods: Fifty-three females with morbid obesity undergoing bariatric surgery were enrolled. Serum parameters and anthropometric measures were obtained at baseline and 3 to 12 months post surgery.

Results: During the 12-month observation period, Hsp60 decreased significantly from 31.6 ± 4.7 ng/mL at baseline to 22.3 ± 3.0 ng/mL (3 months), 26.5 ± 5.5 (6 months), and 21.1 ± 3.3 ng/mL (12 months). Preoperatively, Hsp60 concentrations correlated positively with total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B (ApoB) and negatively with adiponectin. At the end of the observation period, serum Hsp60 positively correlated with triglycerides, ApoB, HbA , and C-reactive protein (CRP). Patients in the highest quartile of serum Hsp60 were characterized by significantly elevated CRP and interleukin 6 independently of BMI, glycemia, and insulinemia. At baseline and 12 months after surgery, Hsp60 positively correlated with the ApoB/ApoA1 ratio and the cholesterol/high-density lipoprotein cholesterol ratio.

Conclusions: Hsp60 concentrations are elevated in morbid obesity and decreased after surgery-induced weight loss. Their correlation with inflammatory markers and cardiovascular risk might link obesity and cardiovascular disease.
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http://dx.doi.org/10.1002/oby.22014DOI Listing
December 2017

The advanced-DiaRem score improves prediction of diabetes remission 1 year post-Roux-en-Y gastric bypass.

Diabetologia 2017 10 21;60(10):1892-1902. Epub 2017 Jul 21.

Institute of Cardiometabolism and Nutrition (ICAN), Nutrition Department, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, 46-83 Boulevard de l'Hôpital, F-75013, Paris, France.

Aims/hypothesis: Not all people with type 2 diabetes who undergo bariatric surgery achieve diabetes remission. Thus it is critical to develop methods for predicting outcomes that are applicable for clinical practice. The DiaRem score is relevant for predicting diabetes remission post-Roux-en-Y gastric bypass (RYGB), but it is not accurate for all individuals across the entire spectrum of scores. We aimed to develop an improved scoring system for predicting diabetes remission following RYGB (the Advanced-DiaRem [Ad-DiaRem]).

Methods: We used a retrospective French cohort (n = 1866) that included 352 individuals with type 2 diabetes followed for 1 year post-RYGB. We developed the Ad-DiaRem in a test cohort (n = 213) and examined its accuracy in independent cohorts from France (n = 134) and Israel (n = 99).

Results: Adding two clinical variables (diabetes duration and number of glucose-lowering agents) to the original DiaRem and modifying the penalties for each category led to improved predictive performance for Ad-DiaRem. Ad-DiaRem displayed improved area under the receiver operating characteristic curve and predictive accuracy compared with DiaRem (0.911 vs 0.856 and 0.841 vs 0.789, respectively; p = 0.03); thus correcting classification for 8% of those initially misclassified with DiaRem. With Ad-DiaRem, there were also fewer misclassifications of individuals with mid-range scores. This improved predictive performance was confirmed in independent cohorts.

Conclusions/interpretation: We propose the Ad-DiaRem, which includes two additional clinical variables, as an optimised tool with improved accuracy to predict diabetes remission 1 year post-RYGB. This tool might be helpful for personalised management of individuals with diabetes when considering bariatric surgery in routine care, ultimately contributing to precision medicine.
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http://dx.doi.org/10.1007/s00125-017-4371-7DOI Listing
October 2017

The FAT Score, a Fibrosis Score of Adipose Tissue: Predicting Weight-Loss Outcome After Gastric Bypass.

J Clin Endocrinol Metab 2017 07;102(7):2443-2453

Institute of Cardiometabolism and Nutrition (ICAN) F-75013 Paris France.

Context: Bariatric surgery (BS) induces major and sustainable weight loss in many patients. Factors predicting poor weight-loss response (PR) need to be identified to improve patient care. Quantification of subcutaneous adipose tissue (scAT) fibrosis is negatively associated with post-BS weight loss, but whether it could constitute a predictor applicable in clinical routine remains to be demonstrated.

Objective: To create a semiquantitative score evaluating scAT fibrosis and test its predictive value on weight-loss response after Roux-en-Y gastric bypass (RYGB).

Methods: We created a fibrosis score of adipose tissue (FAT score) integrating perilobular and pericellular fibrosis. Using this score, we characterized 183 perioperative scAT biopsy specimens from severely obese patients who underwent RYGB (n = 85 from a training cohort; n = 98 from a confirmation cohort). PR to RYGB was defined as <28% of total weight loss at 1 year (lowest tertile). The link between FAT score and PR was tested in univariate and multivariate models.

Results: FAT score was directly associated with increasing scAT fibrosis measured by a standard quantification method (P for trend <0.001). FAT score interobserver agreement was good (κ = 0.76). FAT score ≥2 was significantly associated with PR. The association remained significant after adjustment for age, diabetes status, hypertension, percent fat mass, and interleukin-6 level (adjusted odds ratio, 3.6; 95% confidence interval, 1.8 to 7.2; P = 0.003).

Conclusion: The FAT score is a new, simple, semiquantitative evaluation of human scAT fibrosis that may help identify patients with a potential limited weight-loss response to RYGB.
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http://dx.doi.org/10.1210/jc.2017-00138DOI Listing
July 2017

Roux-en-Y gastric bypass for the treatment of severe complications after omega-loop gastric bypass.

Surg Obes Relat Dis 2017 Jun 9;13(6):988-994. Epub 2016 Dec 9.

Department of Digestive, Oncologic and Metabolic Surgery, Hôpital Ambroise Paré, Boulogne-Billancourt, France; Université Paris Saclay, UFR des sciences de la santé Simone Veil, Montigny-le-Bretonneux, France.

Background: Omega-loop gastric bypass (OLGB) may be associated with severe complications, including anastomotic leak, refractory ulcer or stenosis, undernutrition, and disabling digestive disorders (chronic diarrhea, steatorrhea, bile reflux, and vomiting). OLGB conversion to Roux-en-Y gastric bypass (RYGB) was suggested to treat these complications.

Objectives: To evaluate the efficacy and risk of severe complications after OLGB conversion to RYGB.

Setting: University hospital.

Methods: Retrospective analysis between October 2011 and June 2016.

Results: Seventeen patients underwent OLGB conversion to RYGB. Fourteen patients (82%) presented at least 1 disabling digestive disorder. Before conversion, 10 patients (58.8%) received nutritional support for undernutrition. There was no postoperative mortality. Seven patients (41.1%) developed major adverse events (<90 d). At conversion, the average weight, body mass index, and percent of excess weight loss for the population without undernutrition (n = 7) were 103.7±24 kg, 38.7±6.8 kg/m², and 37%±33%, respectively. These values were 85±18.3 kg, 30.6±4.7 kg/m², and 73.3%±21.5%, respectively, at 2 years. In patients with undernutrition (n = 10), the average weight, body mass index, and percent of excess weight loss were 52.2±16.5 kg, 18.7±5.9 kg/m², and 149.3%±46.5%, respectively, before nutritional support and 58.9±14.7 kg, 21.1±5.2 kg/m², and 132.7%±39.1%, respectively, at revisional surgery. At 2 years the values were 71±5.6 kg, 24.3±2.2 kg/m², and 104.6%±15.2%, respectively. The patients experienced significant improvements in hypoalbuminemia, anemia, and vitamin/trace element deficiencies. The disabling digestive disorders resolved in 85% of patients.

Conclusion: The conversion of OLGB to RYGB for severe complications allows for weight correction in patients with undernutrition, reduces disabling digestive disorders, and improves the nutritional status of patients. However, the conversion is associated with high morbidity.
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http://dx.doi.org/10.1016/j.soard.2016.12.003DOI Listing
June 2017

Mental Health Support Provided Throughout the Bariatric Surgery Clinical Pathway in French Specialized Care Centers for Obesity.

Obes Surg 2017 03;27(3):802-810

Laboratoire de Psychopathologie et Processus de Santé, EA 4057 (LPPS), Université Paris Descartes, Sorbonne Paris Cité, 71, avenue Édouard Vaillant, 92774, Boulogne-Billancourt Cedex, France.

Objective: Pre-operative psychological assessment is recommended by international guidelines for bariatric surgery candidates. Thereby, service teams caring for bariatric patients should include at least one mental health provider (e.g., a psychologist or psychiatrist). The objective of this study was to evaluate the psychology and psychiatry resources and practices in the 37 specialized obesity centers (CSOs) created by the French Ministry of Health.

Materials And Methods: CSO coordinators were contacted by e-mail to collect general information on the centers (e.g., number of bariatric operations). Secondly, psychologists and psychiatrists of each center completed an anonymous questionnaire assessing their professional practices and their organization of care pathways.

Results: The vast majority of CSO coordinators (81%, n = 26/32) answered our survey. These results show significant differences and shortages in terms of the psychology/psychiatry resources available. Most of the psychologists (n = 26/31) and psychiatrists (n = 10/10) stated that they systematically meet new patients only before surgery (56%) or both before and after the operation (30%); however, some psychologists and psychiatrists (14%) do not systematically meet all the patients (before and/or after surgery). Nevertheless, all the professionals provide psychology assessments, and about 75% of them offer a psychological follow-up, indicating a similarity regarding the practices of psychologists and psychiatrists.

Conclusion: Our results highlight the place of psychological/psychiatric evaluations in French CSOs and emphasize the absence of mental health providers in several of these services. Post-operative psychological follow-up is not usually provided. It would be appropriate to create clear recommendations for post-operative psychological or psychiatric long-term follow-up.
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http://dx.doi.org/10.1007/s11695-016-2498-0DOI Listing
March 2017

Systematic review of bariatric surgery liver biopsies clarifies the natural history of liver disease in patients with severe obesity.

Gut 2017 09 24;66(9):1688-1696. Epub 2016 Nov 24.

Nutrition Department, Institute of Cardiometabolism and Nutrition (ICAN), Pitié-Salpêtrière Hospital, (AP-HP), University Pierre et Marie Curie, Paris, France.

Objective: Non-alcoholic fatty liver disease (NAFLD) is a frequent complication of morbid obesity, but its severity varies greatly and thus there is a strong need to better define its natural history in these patients.

Design: Liver biopsies were systematically performed in 798 consecutive patients with severe obesity undergoing bariatric surgery. Histology was compared with clinical, biological, anthropometrical and body composition characteristics.

Results: Patients with presumably normal liver (n=179, 22%) were significantly younger at bariatric surgery than patients with NAFLD (37.0 vs 44.4 years, p<0.0001). However, both groups showed quite similar obesity duration, since patients with presumably normal liver reported the onset of obesity at a significantly younger age than those with NAFLD (14.8 vs 20.0 year, p<0.0001). The trunk/limb fat mass ratio increased according to liver disease severity (presumably normal liver: 1.00, steatosis: 1.21, non-alcoholic steatohepatitis (NASH): 1.34, p<0.0001), although the total body fat mass decreased (presumably normal liver: 50%, steatosis: 49.1%, NASH: 47.4%, p<0.0001). The volume of subcutaneous adipocytes increased according to severity of liver disease but only in female patients (presumably normal liver: 8543 picolitres, steatosis: 9156 picolitres, NASH: 9996 picolitres).

Conclusions: These results suggest that young adults are more prone to store fat in subcutaneous tissue and reach the threshold of bariatric surgery indication before their liver is damaged. A shift of fat storage from subcutaneous to visceral adipose tissue compartment is associated with liver damages. Liver might also be targeted by subcutaneous hypertrophic adipocytes in females since hypertrophic adipocytes are more exposed to lipolysis and to the production of inflammatory mediators.
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http://dx.doi.org/10.1136/gutjnl-2016-312238DOI Listing
September 2017

The effect of morbid obesity on morphine glucuronidation.

Pharmacol Res 2017 04 5;118:64-70. Epub 2016 Sep 5.

Inserm, UMR-S 1144 Université Paris Descartes-Paris Diderot, Variabilité de réponse aux psychotropes, France; Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Pharmacokinetics and Pharmacochemistry Unit, Paris F-75014, France. Electronic address:

The purpose of the present work was to study the change in morphine metabolic ratio in obese subjects before and after Roux-en-Y Gastric Bypass (RYGB) and to identify clinical and/or biological factors associated with this change. The pharmacokinetics (PK) of oral morphine (30mg), morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) was performed in patients before (n=25; mean BMI=43.2 (35.4-61.9)kg/m), 7-15days (n=16) and 6 months after RYGB (n=19; mean BMI=32.3 (25.4-46.0)kg/m). Morphine C and AUC were significantly increased and morphine T significantly shortened at 6 months after RYGB compared with preoperative data, indicating an important increase in the rate and extent of morphine absorption. The morphine metabolic ratio M3G+M6G/Morphine, decreased significantly from the preoperative to 6 months postoperative period with an average of -26% (range -74%; +21%; p=0.004), but not in the immediate post-operative period. The change in morphine metabolic ratio was associated with a change in BMI, fat mass in kg, and triglyceride levels (rho=0.5, p≤0.04). The degree of change in several markers of low-grade inflammation, or the level of liver steatosis and fibrosis before surgery, was not associated with the change in morphine metabolic ratios. Our findings indicate that RYGB-induced weight loss significantly decreases morphine metabolic ratio, arguing for an effect of morbid obesity on glucuronidation. With glucuronide exposure at 6 months similar to preoperative values, a higher morphine AUC should encourage reducing morphine dosage in patients undergoing RYGB and chronically receiving immediate-release oral morphine.
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http://dx.doi.org/10.1016/j.phrs.2016.08.031DOI Listing
April 2017

AdipoScan: A Novel Transient Elastography-Based Tool Used to Non-Invasively Assess Subcutaneous Adipose Tissue Shear Wave Speed in Obesity.

Ultrasound Med Biol 2016 10 26;42(10):2401-13. Epub 2016 Jul 26.

R&D Department, Echosens, Paris, France.

We describe a novel device called the AdipoScan that was adapted from the FibroScan to specifically assess shear wave speed (SWS) in human abdominal subcutaneous adipose tissue (scAT). Measurement reproducibility was assessed on tissue-mimicking phantoms with and without repositioning, with resultant coefficients of variation of 1% and 0%, respectively, as well as in vivo (14% and 7%, respectively). The applicability of the AdipoScan was tested on 19 non-obese volunteers, and a scAT thickness >2 cm was found to be mandatory to perform a valid measurement. Abdominal scAT SWS was assessed in 73 severely obese subjects, all candidates for bariatric surgery. Subcutaneous AT SWS was positively associated with scAT fibrosis and obesity-related co-morbidities such as hypertension, glycemic status, dyslipidemia and liver dysfunction. These results suggest that the AdipoScan could be a useful non-invasive tool to evaluate scAT fibrosis and metabolic complications in obesity. Further investigation is required to evaluate the relevance of using the AdipoScan to predict patient weight trajectories and metabolic outcomes after bariatric surgery.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2016.06.016DOI Listing
October 2016

Effect of Bariatric Surgery-Induced Weight Loss on Platelet Count and Mean Platelet Volume: a 12-Month Follow-Up Study.

Obes Surg 2017 02;27(2):387-393

Department of Digestive, Oncologic and Metabolic Surgery, Ambroise Paré Hospital, Boulogne-Billancourt, France.

Background: Abdominal obesity is strongly correlated with cardiovascular risk and associated with platelet hyperactivity. This hyperactivity is associated with an increase in mean platelet volume (MPV). Few data are available about changes in platelet counts and MPV in obese patients after bariatric surgery (BS). The purpose of this study was to describe quantitative and qualitative changes in the platelet lineage after BS.

Methods: One hundred twenty-eight consecutive patients were included. The mean age was 43 ± 12 years, 77 % of patients were female, and the mean preoperative BMI was 44 ± 6 kg/m. Ninety patients (71 %) had a Roux-en-Y gastric bypass (RYGBP), and 38 (29 %) had a sleeve gastrectomy (SG). Patients were evaluated preoperatively, and postoperative follow-up was performed at 3, 6, and 12 months. The postoperative evaluation included blood samples for full blood count (FBC), including measure of mean platelet volume (MPV).

Results: At the 12-month follow-up, the reduction in preoperative weight was 29 ± 9 %. We showed a significant decrease in platelet count (245 ± 62 vs. 234 ± 54 G/L; p = 0.0015) found in parallel with a non-significant decrease in MPV (9.27 ± 1.1 vs. 9.22 ± 1.05; p = 0.34). With regard to the intervention type, SG caused a more significant decrease in platelet count than RYGBP (p = 0.02). There was no significant difference in MPV variations between the two groups (p = 0.08).

Conclusions: Our results suggest that BS has a positive impact on platelet metabolism, possibly mediated by weight loss. These data need to be confirmed to understand the multifactorial benefits of BS on cardiovascular risk in obese patients.
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http://dx.doi.org/10.1007/s11695-016-2292-zDOI Listing
February 2017

Quantitative Atlas of Cytochrome P450, UDP-Glucuronosyltransferase, and Transporter Proteins in Jejunum of Morbidly Obese Subjects.

Mol Pharm 2016 08 19;13(8):2631-40. Epub 2016 Jul 19.

Inserm, UMR-S 1144 Université Paris Descartes-Paris Diderot, Variabilité de réponse aux psychotropes , Paris F-75010, France.

Protein expression levels of drug-metabolizing enzymes and transporters in human jejunal tissues excised from morbidly obese subjects during gastric bypass surgery were evaluated using quantitative targeted absolute proteomics. Protein expression levels of 15 cytochrome P450 (CYP) enzymes, 10 UDP-glucuronosyltransferase (UGT) enzymes, and NADPH-P450 reductase (P450R) in microsomal fractions from 28 subjects and 49 transporters in plasma membrane fractions from 24 of the same subjects were determined using liquid chromatography-tandem mass spectrometry. Based on average values, UGT1A1, UGT2B15, UGT2B17, SGLT1, and GLUT2 exhibited high expression levels (over 10 fmol/μg protein), though UGT2B15 expression was detected at a high level in only one subject. CYP2C9, CYP2D6, CYP3A5, UGT1A6, P450R, ABCG2, GLUT5, PEPT1, MCT1, 4F2 cell-surface antigen heavy chain (4F2hc), LAT2, OSTα, and OSTβ showed intermediate levels (1-10 fmol/μg protein), and CYP1A1, CYP1A2, CYP1B1, CYP2C18, CYP2C19, CYP2J2, CYP3A7, CYP4A11, CYP51A1, UGT1A3, UGT1A4, UGT1A8, UGT2B4, ABCC1, ABCC4, ABCC5, ABCC6, ABCG8, TAUT, OATP2A1, OATP2B1, OATP3A1, OATP4A1, OCTN1, CNT2, PCFT, MCT4, GLUT4, and SLC22A18 showed low levels (less than 1 fmol/μg protein). The greatest interindividual difference (364-fold) was detected for UGT2B17. However, differences in expression levels of other quantified UGTs (except UGT2B15 and UGT2B17), CYPs (except CYP1A1 and CYP3A5), and P450R, and all quantified transporters, were within 10-fold. Expression levels of CYP1A2 and GLUT4 were significantly correlated with body-mass index. The levels of 4F2hc showed significant gender differences. Smokers showed increased levels of UGT1A1 and UGT1A3. These findings provide a basis for understanding the changes in molecular mechanisms of jejunal metabolism and transport, as well as their interindividual variability, in morbidly obese patients.
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http://dx.doi.org/10.1021/acs.molpharmaceut.6b00085DOI Listing
August 2016

Conversion of sleeve gastrectomy to Roux-en-Y gastric bypass: an audit of 34 patients.

Surg Obes Relat Dis 2016 Nov 2;12(9):1646-1651. Epub 2016 Mar 2.

AP-HP, Department of Digestive, Oncologic and Metabolic Surgery, Hôpital Ambroise Paré, Boulogne-Billancourt, France; UVSQ, UFR des sciences de la santé Simone Veil, 78180, Montigny-le-Bretonneux, France.

Background: Weight loss failure and proton pomp inhibitor (PPI)-resistant gastroesophageal reflux diseases (GERD) after sleeve gastrectomy (SG) are frequently encountered.

Objectives: The aim of this study was to evaluate the efficacy and risks of SG conversion to Roux-en-Y gastric bypass (RYGB) in the case of weight loss failure or severe GERD.

Setting: University hospitals.

Methods: Between March 2007 and December 2014, 34 patients with history of SG underwent RYGP. A retrospective analysis of a prospectively collected database was undertaken.

Results: Among 34 patients, 31 underwent revisional surgery for weight loss failure and 3 for PPI-resistant GERD. Six patients in the weight loss failure group had symptomatic GERD that was effectively treated with PPIs. The average body mass index (BMI) was 53±11 kg/m2 before SG. A laparoscopic approach was performed in 94% of patients. There was no postoperative mortality. Major adverse events (<90 days) occurred in 4 patients (11.7%). The mean length of stay was 6.7±2.8 days. At the time of revisional surgery, the mean BMI, percentage excess weight loss, and percentage weight loss were 44.7±9.8 kg/m2, 33.6±27.1%, and 16±9.7%, respectively, compared with 40.9±8.5 kg/m2, 63.1±36.2%, and 23.8±14% at 3 years. The GERD was resolved in all patients, allowing the cessation of PPI medication.

Conclusion: Laparoscopic conversion of SG to RYGB is feasible and it allows improvement in secondary weight loss and GERD, but at the cost of high morbidity.
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http://dx.doi.org/10.1016/j.soard.2016.02.039DOI Listing
November 2016

Increased Basement Membrane Components in Adipose Tissue During Obesity: Links With TGFβ and Metabolic Phenotypes.

J Clin Endocrinol Metab 2016 06 6;101(6):2578-87. Epub 2016 Apr 6.

Nutrition Department (S.R., C.R., C.P., E.P., S.R., J.T., K.C.), Institute of Cardiometabolism and Nutrition, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris, France; Nutriomics Team (S.R., C.R., C.P., D.L., J.T., K.C.), INSERM, UMR_S U1166, Paris, France; Sorbonne Universités (S.R., C.R., C.P., D.L., J.T., K.C.), Université Pierre et Marie Curie, UMR_S 1166, Paris, France; Plastic Surgery and Mammary Cancer Department (J.-C.B.), Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France; and Visceral Surgery Department (J.-L.B.), Ambroise Paré Hospital, Assistance Publique-Hôpitaux de Paris, Boulogne, France.

Context: Collagen accumulation around adipocytes and vessels (ie, pericellular fibrosis) is a hallmark of obese adipose tissue associated with altered metabolism.

Objective: Our objective was to evaluate components of basement membrane (BM) in adipose tissue, including collagen IV, a major BM component, and its relationships with metabolic parameters and TGFβ isoforms.

Design And Setting: We used immuno-techniques and gene expression approaches to detect BM components in subcutaneous and visceral adipose tissue samples. Adipocytes and endothelial cells were isolated from lean and obese adipose tissue. We also focused on the expression of COL4A1 correlated to metabolic variables in moderate obesity and, in severe obesity before and after bariatric surgery. Using in vitro analysis, we explored the impact of TGFβ isoforms on the expression of inflammatory and extracellular matrix genes in adipocytes and endothelial cells.

Results: BM components were detected around adipocytes and endothelial cells, and were increased in obese adipocytes. COL4A1 expression was positively correlated with insulin-resistance indices in obese subjects and showed less reduction in severely obese subjects with poorer insulin-resistance outcomes 6 months after gastric bypass. COL4A1 expression also correlated with TGFβ1 and TGFβ3 gene expressions in subcutaneous adipose tissue. Stimulating isolated adipocytes and endothelial cells in vitro with these TGFβ isoforms showed an inflammatory and pro-fibrotic phenotype. However, TGFβ1 and TGFβ3 exposure only provoked COL4A1 overexpression in endothelial cells and not in adipocytes.

Conclusion: The disorganization of several BM components, including collagen IV, could contribute to pathological alterations of obese adipose tissue and cells.
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http://dx.doi.org/10.1210/jc.2015-4304DOI Listing
June 2016

Postprandial GLP-1 Secretion After Bariatric Surgery in Three Cases of Severe Obesity Related to Craniopharyngiomas.

Obes Surg 2016 May;26(5):1133-7

Department of Nutrition, Ambroise Paré Hospital, AP-HP, Université de Versailles Saint-Quentin en Yvelines, Boulogne-Billancourt, 92100, France.

Craniopharyngiomas are rare cerebral tumors associated with severe obesity after hypothalamic surgery. A meta-analysis showed significant weight loss at 1 year after bariatric surgery in these patients even though more modest than in common causes of obesity. We hypothesized that this discrepancy could be partly explained by differences in GLP-1 secretion after surgery since patients with craniopharyngioma present a significantly higher degree of insulin resistance and hyperinsulinism than common obese control. We report three cases of bariatric surgery in patients presenting with hypothalamique obesity related to craniopharyngiomas. At 18 months, the mean weight loss was 20 kg with expected insulin resistance decrease. Before surgery, standardized test meal shows abolition of postprandial GLP-1 secretion in all patients with a progressive restoration in the patients with gastric bypass (GBP) surgery.
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http://dx.doi.org/10.1007/s11695-015-1977-zDOI Listing
May 2016
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