Gil Faria

Persistent organic pollutant levels in human visceral and subcutaneous adipose tissue in obese individuals-Depot differences and dysmetabolism implications

BACKGROUND The role of persistent organic pollutants (POPs) with endocrine disrupting activity in the aetiology of obesity and other metabolic dysfunctions has been recently highlighted. Adipose tissue (AT) is a common site of POPs accumulation where they can induce adverse effects on human health. OBJECTIVES To evaluate the presence of POPs in human visceral (vAT) and subcutaneous (scAT) adipose tissue in a sample of Portuguese obese patients that underwent bariatric surgery, and assess their putative association with metabolic disruption preoperatively, as well as with subsequent body mass index (BMI) reduction. METHODS AT samples (n=189) from obese patients (BMI ≥ 35) were collected and the levels of 13 POPs were determined by gas chromatography with electron-capture detection (GC-ECD). Anthropometric and biochemical data were collected at the time of surgery. BMI variation was evaluated after 12 months and adipocyte size was measured in AT samples. RESULTS Our data confirm that POPs are pervasive in this obese population (96.3% of detection on both tissues), their abundance increasing with age (RS=0.310, p<0.01) and duration of obesity (RS=0.170, p<0.05). We observed a difference in AT depot POPs storage capability, with higher levels of ΣPOPs in vAT (213.9 ± 204.2 compared to 155.1 ± 147.4 ng/g of fat, p<0.001), extremely relevant when evaluating their metabolic impact. Furthermore, there was a positive correlation between POP levels and the presence of metabolic syndrome components, namely dysglycaemia and hypertension, and more importantly with cardiovascular risk (RS=0.277, p<0.01), with relevance for vAT (RS=0.315, p<0.01). Finally, we observed an interesting relation of higher POP levels with lower weight loss in older patients. CONCLUSION Our sample of obese subjects allowed us to highlight the importance of POPs stored in AT on the development of metabolic dysfunction in a context of obesity, shifting the focus to their metabolic effects and not only for their recognition as environmental obesogens.

Acute diverticulitis in younger patients: any rationale for a different approach?

AIM To compare the natural history and course of acute diverticulitis in a younger age group with an older population and to evaluate whether younger patients should be managed differently. METHODS This study was a retrospective review of 157 patients treated with acute diverticulitis between January 1, 2004 and December 31, 2007. Diverticulitis was stratified according to the Hinchey classification. Patients were divided into 2 populations: group A ≤ 50 years (n = 31); group B > 50 years (n = 126). Mean patient follow-up was 15 mo. RESULTS The median age was 60 years. A significantly higher proportion of patients in group B presented with complicated diverticulitis (36.5% vs 12.9%, P = 0.01). Recurrence was more frequent in group A (25.8% vs 11.1%, P = 0.03) and the mean time-to-recurrence was shorter (12 mo vs 28 mo, P = 0.26). The most severe recurrent episodes of acute diverticulitis were classified as Hinchey stage I and none of the patients required emergency surgery. In multivariate analysis, only age (P = 0.024) was identified as an independent prognostic factor for recurrence. CONCLUSION Based on the results of this study, the authors recommend that diverticulitis management should be based on the severity of the disease and not on the age of the patient.

Metabolic score: insights on the development and prediction of remission of metabolic syndrome after gastric bypass.

Introduction:Metabolic syndrome (MetS) clusters the most dangerous cardiovascular disease risk factors. Although insulin resistance and central obesity play an important role in the pathogenesis, the factors that determine its development and ultimate remission after Roux-en-Y gastric bypass (RYGB) are not fully understood. Methods:We recruited a prospective cohort of 210 consecutive patients after RYGB between January 2010 and December 2011. Patients were evaluated clinically and with a biochemical profile preoperatively and at 12 months after surgery. Visceral adipose tissue and subcutaneous abdominal adipose tissue samples were collected at surgical intervention. We aimed to identify factors associated with MetS in morbidly obese patients and predictors of its remission 12 months after RYGB. Results:Increasing age (>40 years), male sex, alanine aminotransferase levels and visceral adipose tissue/subcutaneous adipocyte size ratio were independently related to the expression of MetS at the moment of surgery.One year after RYGB, there was a significant decrease in the prevalence of MetS (63.3%–10%; P < 0.001) and in each of its components. A multivariable analysis for the remission of MetS identified that only fasting glucose levels (OR = 13.4; P = 0.01) and duration of obesity (OR = 1.08; P = 0.04) were independently related to the persistence of MetS. A metabolic score (scale of 1–10), consisting of duration of obesity, fasting blood glucose levels, the presence of high blood pressure and low levels of high-density lipoprotein identified 4 different risk categories for the persistence of MetS (area under the curve = 0.848). Conclusions:The metabolic score can be used to predict the remission of MetS after RYGB with high accuracy. Patients in high-risk groups might be managed more aggressively and low-risk patients may have their medication discontinued earlier with extra safety.

Clear Cell Change in Colonic Polyps

In this study, the pathogenesis of clear cell change in colorectal epithelial lesions was studied. A total of 4 cases of clear cell change (1 hyperplasic polyp and 3 adenomas) were characterized using histochemistry, immunohistochemistry, and electron microscopy. All lesions developed in the left colon. In all, 1 adenoma with clear cell dysplastic glands progressed to adenocarcinoma without clear cell change. Clear cell cytoplasmatic vacuoles were negative for glycogen and mucins (MUC 2, MUC 5AC). Ki-67 LI in clear cell adenoma components was lower than in common adenoma components of the same dysplasia grades (while p53 and β-catenin were similarly expressed). Ultrastructural features of clear cell change showed features of lipid-like material. Clear cell change is found in hyperplastic and neoplastic lesions of the colon and is not due to the accumulation of glycogen or mucins. A degenerative nature of clear cell change is suggested by the demonstration of lipid-like material in the vacuoles of clear cells.

Primary gastric adenosquamous carcinoma in a Caucasian woman: a case report

IntroductionMost gastric tumors are adenocarcinomas. Primary gastric adenosquamous carcinoma is a rare malignancy, mostly associated with Asian populations. It constitutes less than one percent of all gastric carcinomas and its clinical presentation is the same as adenocarcinoma. It occurs more frequently in the proximal stomach, usually presents with muscular layer invasion and tends to be found in advanced stages at diagnosis, with a worse prognosis than adenocarcinoma.Case presentationWe report the case of an 84-year-old Caucasian woman with an adenosquamous carcinoma extending to her serosa with lymphatic and venous invasion (T3N1M1). Nodal and hepatic metastasis presented with both cellular types, with dominance of the squamous component.ConclusionsAdenosquamous gastric cancer is a rare diagnosis in western populations. We present the case of a woman with a very aggressive adenosquamous carcinoma with a preponderance of squamous cell component in the metastasis. Several origins have been proposed for this kind of carcinoma; either evolution from adenocarcinoma de-differentiation or stem cell origin might be possible. The hypothesis that a particular histological type of gastric cancer may arise from stem cells might be a field of research in oncological disease of the stomach.

Inflammatory and Cardiometabolic Risk on Obesity: Role of Environmental Xenoestrogens

CONTEXT Some chemicals used in consumer products or manufacturing (eg, plastics, pesticides) have estrogenic activities; these xenoestrogens (XEs) may affect immune responses and have recently emerged as a new risk factors for obesity and cardiovascular disease. However, the extent and impact on health of chronic exposure of the general population to XEs are still unknown. OBJECTIVE The objective of the study was to investigate the levels of XEs in plasma and adipose tissue (AT) depots in a sample of pre- and postmenopausal obese women undergoing bariatric surgery and their cardiometabolic impact in an obese state. DESIGN AND PARTICIPANTS We evaluated XE levels in plasma and visceral and subcutaneous AT samples of Portuguese obese (body mass index ≥ 35 kg/m(2)) women undergoing bariatric surgery. Association with metabolic parameters and 10-year cardiovascular disease risk was assessed, according to menopausal status (73 pre- and 48 postmenopausal). Levels of XEs were determined by gas chromatography with electron-capture detection. Anthropometric and biochemical data were collected prior to surgery. Adipocyte size was determined on tissue sections obtained during surgery. RESULTS Our data show that XEs are pervasive in this obese population. Distribution of individual and concentration of total XEs differed between plasma, visceral AT, and subcutaneous AT, and the pattern of accumulation was different between pre- and postmenopausal women. Significant associations between XE levels and metabolic and inflammatory parameters were found. In premenopausal women, XEs in plasma seem to be a predictor of 10-year cardiovascular disease risk. CONCLUSIONS Our findings point toward a different distribution of XE between plasma and AT in pre- and postmenopausal women, and reveal the association between XEs on the development of metabolic abnormalities in obese premenopausal women.

Age and Weight Loss After Bariatric Surgery: Cause or Consequence?

In spite of its indisputable role in the treatment of obesity,bariatric surgery is not absent of cutbacks and complica-tions. Cumulative experience is allowing the discovery offactors associated with weight loss after bariatric surgery[1], which may allow the development of more selectiveand effective interventions. In this regard, both Contreraset al. [2] and Scozzari et al. [3] reports bring an importantcontribution, by clearly showing that patients’ age nega-tively associates with success in weight loss. In the dis-cussion of their results, the authors consider a range offacts possibly interfering with weight loss in people ofmore advanced age: from differences in energy require-ments to social and psychological aspects and, probably ofgreat importance, an impaired metabolic capacity and alower lipolytic activity.Results obtained by our group [4], in a sample of 163obese patients, showed that, in good agreement with theresults of Scozzari et al., younger patients (<50 years)achieved a greater weight loss after 12 months of follow-up (80 % excess weight loss (EWL) vs 70 % EWL; p=0.01). More interestingly, in the preoperative period and incomparison with older patients, younger (and most respon-sive) patients had significantly lower fasting glucose levels(93 vs 111 mg/dL; p<0.001) [4] and were less contaminat-ed with persistent organic pollutants (POPs) in visceraladipose tissue (168.9±13.7 ng/g of fat vs 311.0±32.7 ng/goffat,p<0.0001) [POPs data to be published]. Specifi-cally in our analysis, the effect of age disappeared afteradjustment for fasting blood glucose levels.As both higher fasting glucose [ 5] levels and higher levels ofPOPs [6] in adipose tissue will decr ease lipolysis, this seems tobe a most important mechanism behind the difficulty of olderpeople to respond to weight-los ing interventions. It would beinteresting to study the influence of age on weight loss by otherinterventions and to further evaluate the capacity of fastingglucose and POPs levels to predict weight loss independentlyof age.

Environmental xenoestrogens contribute to inflammation and cardiometabolic risk during obesity in pre-menopausal women

Background: The development of BMI in early childhood is dependent on socioeconomic factors. Our aim was to explore the impact of parental education level and family income for development of BMI from birth to 8 years age.Methods: 3018 children born in 1998–2006 from the IDEFICS study and register controls were included. Weight and height measurements from birth up to 8 years of age were obtained from the Child Health Services. Parental education and family disposable income, obtained from Statistics Sweden and the Medical Birth Register, were defined as high/low. Obesity was defined by WHO references. Confounders were sex and age of the child, parental origin, maternal smoking and maternal BMI.Results: At birth, the children’s mean BMI (SD) was lower in families of low vs. high income (13,74 (1,35) vs. 13,94 (1,36), p<0.0001). Results remained significant after adjusting for confounders. No differences in birth BMI were detected between children of low and high-educated parents (13,87 (1,37) vs. 13,83 (1,35), p=0.48). From 6 months onwards, children of low-educated parents showed higher mean BMI than children of high-educated. At 8 years, mean BMI in the low/high educated groups were 17.12 (2.44) and 16.38 (1.94), p<0.0001. Results remained significant after adjusting for confounders. Prevalence of obesity in the low and high-educated groups were 11% and 4,1%, p<0,0001. The difference in BMI at 8 years seen in the low/high income group disappeared after adjusting for confounders (17.5 vs. 17.6, p=0,63).Conclusion: Impact of family socioeconomic factors on children’s BMI differs by income and education. The effect of parental education becomes more evident by age up to 8 years of age. Interventions for healthy weight development must start very early in life.Background: Compelling evidence links obesity induced systemic inflammation to the development of chronic kidney disease (CKD). This systemic inflammation may result from exacerbated adipose inflammation. Besides the known detrimental effects of typical pro-inflammatory factors secreted by the adipose tissue (TNF-α, MCP-1 and IL-6) on the kidney, we hypothesize the enhanced obesity-induced secretion of serum amyloid A (SAA), an acute inflammatory protein, to play a key role in aggravating obesity-induced CKD. Methods: Groups of male C57Bl/6J mice (n = 99 in total) were fed a low (10% lard) or high (45% lard) fat diet for a maximum of 52 weeks. Mice were sacrificed after 24, 40 and 52 weeks. Whole blood samples, kidneys and adipose tissues were collected. The development of adipose and renal tissue inflammation was assessed on gene expression and protein level. Adipocytokine levels were measured in plasma samples. Results: A distinct inflammatory phenotype was observed in the adipose tissue of HFD mice prior to renal inflammation, which was associated with an early systemic elevation of TNF-α, leptin and SAA (1A-C). With aging, sclerotic lesions appeared in the kidney, the extent of which was severely aggravated by HFD feeding. Lesions exhibited typical amyloid characteristics (2A) and pathological severity positively correlated with bodyweight (2B). Interestingly, more SAA protein was detected in lesions of HFD mice. Conclusion: Our data suggest a causal link between obesity induced chronic inflammation and AA amyloidosis in C57Bl/6J mice. Though future studies are necessary to prove this causal link and to determine its relevance for the human situation, obesity may hence be considered a risk factor for the development and progression of renal AA amyloidosis in the course of CKD. (Figure Presented).Introduction: Existing treatment programs for obese children prove limited effectiveness and sustainability. Health Information System (HIS) enhanced interventions have the potential for higher accessibility and cost-effectiveness of multi-professional family-based obesity therapy. The aim was not only to modify the patient’s behavior but also to positively influence their family system. Methods: In cooperation with therapists, extremely obese children, their parents, computer scientists and information systems researcher, a mobile HIS was developed, consisting of a tablet PC with photo and patient’s privacy services, relaxation tools and the ability to measure speed of eating by electronic stop watch, emotional parameters by self-assessment manikin mood scale and physical activity by 3-axes accelerometer, Fitbit, combined with telephone interviews. Three groups of each six extremely obese children (BMI > 99.5, median BMI z-score 3.0, age 13.2 2.3 years) were assigned to therapy in either an (1) individual or (2) group setting with HIS, or (3) individual care without HIS. Physical activity, speed of eating and physical and emotional parameters were evaluated before and after 12 months of therapy. All patients and parents gave informed consent for adherence to therapy, monitoring and the use of tablet PC’s. Results: A total of 25% of extremely obese children with HIS and 60% without HIS decreased their BMI-SDS. Children using HIS did not reduce their obesity more than the control group without HIS, if parents did not support their children at home. Those children with parental support did use HIS for activity, mood and nutrition monitoring regularly. Conclusion: In extremely obese children, home support with HIS is only effective, when children are guided by their parents while using HIS. To select appropriate families for HIS home support, careful examination of the family system including their motivation and psychosocial factors is needed.Basel · Freiburg · Paris · London · New York · Chennai · New Delhi · Bangkok · Beijing · Shanghai · Tokyo · Kuala Lumpur · Singapore · Sydney

Open gastrostomy by mini-laparotomy: A comparative study

BACKGROUND Gastrostomy tube feeding is the best option for long lasting nutritional support in patients with dysphagia caused by obstructive tumours of the mouth, pharynx, larynx and ooesophagus or neuromuscular diseases. However, these severely compromised patients often present severe respiratory risks, precluding the use of general anesthesia, sedation or even endoscopy. A simplified open gastrostomy (SOG) under local anesthesia has been in practice in our institution, especially for patients with severe neuromuscular diseases and continuous non-invasive ventilatory support. In this study, we try to compare the surgical outcomes of this technique, with the classical Stamm gastrostomy (SG). MATERIAL AND METHODS This simplified technique uses a minimal vertical midline incision (3 cm), just below the xyphoid process, under local anesthesia. The gastrostomy tube is passed by a left lateral stab wound, inserted in a double purse-string in the gastric wall and pulled to the anterior abdominal wall. No sutures between the stomach and the peritoneum are placed. We retrospectively analyzed the clinical records of 63 consecutive gastrostomies performed upon a 3-year period, 23 of which were by SOG. RESULTS The SG was performed mainly in oncological patients, and SOG in patients with neuromuscular diseases (p < 0.001). In the SOG group, 95,4% (n = 22) of the patients were ASA IV, compared with 74,4% (n = 29) in SG (p = 0,03). The mean operative time was shorter in the simplified technique (37 vs 60 min; p = 0,01). All the surgeries in the SOG group were performed exclusively with local anesthesia and in the Stamm procedure, 47,5% required invasive ventilatory support (p < 0.001). There were no significant differences regarding in-hospital morbi-mortality (p = 0,18). The patients were able to receive adequate nutritional support, and the overall satisfaction of the patients and family/caregivers is very good. CONCLUSION The simplified mini-laparotomy gastrostomy is a safe and effective alternative to other approaches. The association of local anesthesia with a minimal surgical offense and a short operative time render its effectiveness, even in high-risk patients.