Human white and brite adipogenesis is supported by MSCA1 and is impaired by immune cells.

Obesity-associated inflammation contributes to the development of metabolic diseases. Although brite adipocytes have been shown to ameliorate metabolic parameters in rodents, their origin and differentiation remain to be characterized in humans. Native CD45-/CD34+/CD31- cells have been previously described as human adipocyte progenitors. Using two additional cell surface markers, MSCA1 (tissue nonspecific alkaline phosphatase) and CD271 (nerve growth factor receptor), we are able to partition the CD45-/CD34+/CD31- cell population into three subsets. We establish serum-free culture conditions without cell expansion to promote either white/brite adipogenesis using rosiglitazone, or bone morphogenetic protein 7 (BMP7), or specifically brite adipogenesis using 3-isobuthyl-1-methylxanthine. We demonstrate that adipogenesis leads to an increase of MSCA1 activity, expression of white/brite adipocyte-related genes, and mitochondriogenesis. Using pharmacological inhibition and gene silencing approaches, we show that MSCA1 activity is required for triglyceride accumulation and for the expression of white/brite-related genes in human cells. Moreover, native immunoselected MSCA1+ cells exhibit brite precursor characteristics and the highest adipogenic potential of the three progenitor subsets. Finally, we provided evidence that MSCA1+ white/brite precursors accumulate with obesity in subcutaneous adipose tissue (sAT), and that local BMP7 and inflammation regulate brite adipogenesis by modulating MSCA1 in human sAT. The accumulation of MSCA1+ white/brite precursors in sAT with obesity may reveal a blockade of their differentiation by immune cells, suggesting that local inflammation contributes to metabolic disorders through impairment of white/brite adipogenesis. Stem Cells 2015;33:1277-1291.

Long-term evolution of nutritional deficiencies after gastric bypass: an assessment according to compliance to medical care.

OBJECTIVE: To study long-term nutritional deficits based on adherence to a standardized nutritional care after gastric bypass (GBP). BACKGROUND: Long-term prospective data on nutritional complications after GBP are missing. It is not known whether severe deficiencies are prevented by standard multivitamin supplementation and what parameters are influenced by patient adherence to nutritional care. DESIGN: One hundred forty-four consecutive subjects from our prospective database (90% women, initial body mass index: 48 ± 15 kg/m2, age: 43 ± 10 years) who underwent GBP more than 3 years before the study were assessed. Multivitamins were systematically prescribed after GBP, and additional supplements were introduced if deficiencies were recorded during follow-up. We identified a group of 66 compliant subjects who attended yearly medical visits and a group of 32 noncompliant subjects who were recalled because they had not attended any visit for more than 2 years. RESULTS: Weight loss was 42 ± 14 kg at 3 years or later. The number of nutritional deficits per subject was 3.2 ± 2.3 before surgery and did not significantly increase between 1 and 3 years or later after GBP (3.4 ± 2.0 and 3.5 ± 2.3, respectively). However, specific nutritional deficits occurred despite long-term multivitamin supplementation, including vitamins B1, B12, and D and iron. Noncompliant subjects had more deficits than compliant subjects (4.2 ± 1.9 vs 2.9 ± 2.0 deficits per patient, P < 0.01) and the number of deficits correlated with the time from last visit (r = 0.285, P < 0.01). CONCLUSIONS: Lifelong medical care is required to maintain a good nutritional status after GBP. Monitoring of nutritional parameters is necessary to add supplementation for deficits that are not prevented by multivitamin preparations.

Consequences of Small Intestinal Bacterial Overgrowth in Obese Patients Before and After Bariatric Surgery.

BACKGROUND AND AIMS: Small intestinal bacterial overgrowth (SIBO) has been described in obese patients. The aim of this study was to prospectively evaluate the prevalence and consequences of SIBO in obese patients before and after bariatric surgery. PATIENTS AND METHODS: From October 2001 to July 2009, in obese patients referred for bariatric surgery (BMI >40 kg/m2 or >35 in association with comorbidities), a glucose hydrogen (H2) breath test (BT) was performed before and/or after either Roux-en-Y gastric bypass (RYGBP) or adjustable gastric banding (AGB) to assess the presence of SIBO. Weight loss and serum vitamin concentrations were measured after bariatric surgery while a multivitamin supplement was systematically given. RESULTS: Three hundred seventy-eight (mean ± SD) patients who performed a BT before and/or after surgery were included: before surgery, BT was positive in 15.4 % (55/357). After surgery, BT was positive in 10 % (2/20) of AGB and 40 % (26/65) of RYGBP (p < 0.001 compared to preoperative situation). After RYGBP, patients with positive BT had similar vitamin levels, a lower caloric intake (983 ± 337 vs. 1271 ± 404 kcal/day, p = 0.014) but a significant lower weight loss (29.7 ± 5.6 vs. 37.7 ± 12.9 kg, p = 0.002) and lower percent of total weight loss (25.6 ± 6.0 vs. 29.2 ± 6.9 %, p = 0.044). CONCLUSION: In this study, SIBO is present in 15 % of obese patients before bariatric surgery. This prevalence does not increase after AGB while it rises up to 40 % of patients after RYGBP and it is associated with lower weight loss.

Comparison of the incidence of cholelithiasis after sleeve gastrectomy and Roux-en-Y gastric bypass in obese patients: a prospective study.

BACKGROUND: Although the risk of cholelithiasis (CL) increases in patients after Roux-en-Y gastric bypass (RYGB), no prospective study has yet assessed the incidence of CL after sleeve gastrectomy (SG). OBJECTIVES: To compare, prospectively, the incidence and predictive factors for CL after both procedures. METHODS: A postoperative abdominal ultrasound follow-up was proposed to all patients with an intact gallbladder and who underwent RYGB or SG in Hôpital Louis Mourier from 2008 onward. RESULTS: At least one ultrasound was performed on one hundred and sixty patients between 6 and 12 months postsurgery, 43 after SG and 117 after RYGB. Age, gender, initial body-mass index, co-morbidities were similar in both groups. Weight loss (WL) at 6 months was significantly lower after SG than after RYGB (26.9 ± 9.2 and 31.3 ± 7.5 kg, respectively = .001). The incidences of CL after SG and RYGB were similar (28% versus 34% respectively, P = .57). Most cases of CL occurred in the first year post surgery. During the follow-up, 12% and 13% of patients who underwent SG and RYGB, respectively, became symptomatic. WL of>30 kg at 6 months was a risk factor for CL after bariatric surgery, but we did not find any preoperative predictive factor for gallstone formation. CONCLUSIONS: Despite lower WL after SG, the incidence of CL after SG and RYGB was similar at 2 years. Our results suggest that rapid WL is the main element leading to gallstone formation after both procedures.

Comparison of nutritional status during the first year after sleeve gastrectomy and Roux-en-Y gastric bypass.

Sleeve gastrectomy (SG) is supposed to induce fewer nutritional deficiencies than gastric bypass (GBP). However, few studies have compared nutritional status after these two procedures, and the difference in weight loss (WL) between procedures may alter the results. Thus, our aim was to compare nutritional status after SG and GBP in subjects matched for postoperative weight. Forty-three subjects who underwent SG were matched for age, gender, and 6-month postoperative weight with 43 subjects who underwent GBP. Dietary intakes (DI), metabolic (MP), and nutritional parameters (NP) were recorded before and at 6 and 12 months after both procedures. Multivitamin supplements were systematically prescribed after surgery. Before surgery, BMI, DI, MP, and NP were similar between both groups. After surgery, LDL cholesterol, serum prealbumin, vitamin B12, urinary calcium, and vitamin D concentrations were lower after GBP than after SG, whereas WL and DI were similar after both procedures. However, the total number of deficiencies did not increase after surgery regardless of the procedure. In addition, we found a significant increase in liver enzymes and a greater decrease in C-reactive protein after GBP. In conclusion, during the first year after surgery, in patients with the same WL and following the same strategy of vitamin supplementation, global nutritional status was only slightly impaired after SG and GBP. However, some nutritional parameters were specifically altered after GBP, which could be related to malabsorption or other mechanisms, such as alterations in liver metabolism.

Serum vitamin D increases with weight loss in obese subjects 6 months after Roux-en-Y gastric bypass.

BACKGROUND: Malabsorptive surgical procedures lead to deficiencies in fat-soluble vitamins. However, results concerning serum vitamin D (25OHD) after gastric bypass (GBP) are controversial. The aim of the study was to assess the influence of GBP on 25OHD and calcium metabolism. METHODS: Parameters of calcium metabolism were evaluated in 202 obese subjects before and 6 months after GBP. Thirty of them were matched for age, gender, weight, skin color, and season with 30 subjects who underwent sleeve gastrectomy (SG). A multivitamin preparation that provides 200 to 500 IU vitamin D3 per day was systematically prescribed after surgery. RESULTS: In the 202 patients after GBP, serum 25OHD significantly increased from 13.4 ± 9.1 to 22.8 ± 11.3 ng/ml (p < 0.0001), whereas parathyroid hormone (PTH) did not change. Despite a decrease in calcium intake (p < 0.0001) and urinary calcium/creatinine ratio (p = 0.015), serum calcium increased after GBP (p < 0.0001). Preoperatively, 91 % of patients had 25OHD insufficiency (< 30 ng/ml), 80% deficiency (< 20 ng/ml), and 19% secondary hyperparathyroidism (> 65 pg/ml) vs. 76, 44, and 17%, respectively, following GBP. Serum 25OHD was negatively correlated with BMI at 6 months after GBP (R = -0.299, p < 0.0001). In the two groups of 30 subjects, serum 25OHD and PTH did not differ at 6 months after GBP or SG. CONCLUSIONS: At 6 months after GBP, serum 25OHD significantly increased in subjects supplemented with multivitamins containing low doses of vitamin D. These data suggest that weight loss at 6 months after surgery has a greater influence on vitamin D status than malabsorption induced by GBP.

Cytoreductive surgery associated to hyperthermic intraperitoneal chemoperfusion for desmoplastic round small cell tumor with peritoneal carcinomatosis in young patients.

PURPOSE: Desmoplastic round small cell tumor (DRSCT) is a rare intraabdominal mesenchymal tissue neoplasm in young patients and spreads through the abdominal cavity. Its prognosis is poor despite a multimodal therapy including chemotherapy, radiotherapy, and surgical cytoreduction (CS). hyperthermic intraperitoneal chemotherapy (HIPEC) is considered as an additional strategy in the treatment of peritoneal carcinomatosis; for this reason, we planned to treat selected cases of children with DRSCT using CS and HIPEC. METHODS: Peritoneal disease extension was evaluated according to Gilly classification. Surgical cytoreduction was considered as completeness of cytoreduction-0 when no macroscopic nodule was residual; HIPEC was performed according to the open technique. RESULTS: We described 3 cases: the 2 first cases were realized for palliative conditions and the last one was operated on with curative intent. There was no postoperative mortality. One patient was reoperated for a gallbladder perforation. There was no other complication related to HIPEC procedure. CONCLUSIONS: Surgical cytoreduction and HIPEC provide a local alternative approach to systemic chemotherapy in the control of microscopic peritoneal disease in DRSCT, with an acceptable morbidity, and may be considered as a potential beneficial adjuvant waiting for a more specific targeted therapy against the fusion protein.

Predictive factors of weight loss 1 year after laparoscopic gastric bypass in obese patients.

BACKGROUND: Substantial weight loss is achieved in majority of severely obese subjects undergoing laparoscopic gastric bypass (LGBP) but some fail to obtain expected results. Our aim was to identify preoperative factors that could influence weight loss (WL) 1 year after LGBP. METHODS: We studied the predictive value of clinical, biological, and dietary preoperative factors on weight loss in obese patients referred for LGBP. WL was assessed according to mean absolute weight loss (AWL) and mean percent excess weight loss (%EWL) 1 year after LGBP. RESULTS: One hundred twenty-three subjects were included (112 women, age 42 ± 10 years; weight 127 ± 23 kg; BMI 47 ± 8 kg/m(2)). Mean AWL was 39.4 ± 10.5 kg at 1 year, corresponding to a mean %EWL of 70.5 ± 21.2%. AWL was positively correlated with initial weight, BMI, and energy intake and negatively with age, female sex, and treatment for hypertension and diabetes. %EWL was negatively correlated with initial weight, BMI, and positively correlated with triglycerides and ferritinemia. In multivariate analysis, %EWL was negatively correlated only with initial BMI (p < 0.001). AWL was positively correlated with initial BMI and male sex (both p < 0.001), and negatively correlated with protein intake (p = 0.039) and treatment for diabetes (p = 0.021), but not with biomarkers of diabetes and insulin resistance. CONCLUSION: Initial BMI appears to be a strong determinant of individual WL, but predictive factors differ when WL was expressed as %EWL or AWL. The treatment of diabetes rather than diabetes itself appears to affect WL.

Temporary restoration of digestive continuity after laparoscopic gastric bypass to allow endoscopic sphincterotomy and retrograde exploration of the biliary tract.

The prevalence of morbid obesity is rapidly increasing worldwide. As surgery has been recognized to be the only effective treatment for morbid obesity, the number of bariatric procedure realized each year has dramatically increased. Among all the surgical options, gastric bypass in considered as the gold standard. A possible drawback of this operation is the difficult access to the excluded proximal intestinal tract and, consequently, to the biliary tract. As gallstone formation may be frequent after a rapid weight loss induced by surgery, surgeons could be frequently asked to face the need of exploration of the biliary tree after anatomical changes induced by this kind of surgery. Many technical solutions, mainly based on a combined laparoscopic and endoscopic approach, have been proposed by several authors to face this problem. We herein describe an original technique to allow endoscopic exploration of biliary tract after a laparoscopic gastric bypass based on temporary restoration of physiological digestive continuity followed by re-establishment of the Roux-en-Y loop.

Iterative cytoreductive surgery associated with hyperthermic intraperitoneal chemotherapy for treatment of peritoneal carcinomatosis of colorectal origin with or without liver metastases.

INTRODUCTION: The aim of this study was to evaluate the results of an aggressive strategy in patients presenting peritoneal carcinomatosis (PC) from colorectal cancer with or without liver metastases (LMs) treated with cytoreductive surgery (CS) and hyperthermic intraperitoneal chemotherapy (HIPEC). PATIENTS AND METHODS: The population included 43 patients who had 54 CS+HIPEC for colorectal PC from 1996 to 2006. Sixteen patients (37%) presented LMs. Eleven patients (25%) presented occlusion at the time of PC diagnosis. Ascites was present in 12 patients (28%). Seventy-seven percent of the patients were Gilly 3 (diffuse nodules, 5-20 mm) and Gilly 4 (diffuse nodules>20 mm). The main endpoints were morbidity, mortality, completeness of cancer resection (CCR), and actuarial survival rates. RESULTS: The CS was considered as CCR-0 (no residual nodules) or CCR-1 (residual nodules <5 mm) in 30 patients (70%). Iterative procedures were performed in 26% of patients. Three patients had prior to CS + HIPEC, 10 had concomitant minor liver resection, and 3 had differed liver resections (2 right hepatectomies) 2 months after CS + HIPEC. The mortality rate was 2.3% (1 patient). Seventeen patients (39%) presented one or multiple complications (per procedure morbidity = 31%). Complications included deep abscess (n = 6), wound infection (n = 5), pleural effusion (n = 5), digestive fistula (n = 4), delayed gastric emptying syndrome (n = 4), and renal failure (n = 3). Two patients (3.6%) were reoperated. The median survival was 38.4 months (CI, 32.8-43.9). Actuarial 2- and 4-year survival rates were 72% and 44%, respectively. The survival rates were not significantly different between patients who had CS + HIPEC for PC alone (including the primary resection) versus those who had associated LMs resection (median survival, 35.3 versus 36.0 months, P = 0.73). CONCLUSION: Iterative CS + HIPEC is an effective treatment in PC from colorectal cancer. The presence of resectable LMs associated with PC does not contraindicate the prospect of an oncologic treatment in these patients.