Giancarlo Micheletto

Treatment of morbid obesity with Intragastric balloon in association with diet

Background: The BioEnterics Intragastric Balloon (BIB®, BioEnterics, Santa Barbara, CA) in association with restricted diet has been used for the treatment of obesity and morbid obesity. Methods: Since March 1998, 322 BIB were placed in 281 obese and morbidly obese patients; 73 patients were male and 208 female; mean age was 41.6 years (21-70); mean weight was 117.4 kg (67- 229); mean BMI was 41.8 kg/m2 (29-81); % excess weight was 62% (10-216). The balloon was inserted and removed endoscopically under general anesthesia. Patients were given a balanced diet of 1000 kcal/day.Also, for 18 months we compared 42 obese patients treated only with 1000 kcal/day diet (group A) with 31 obese patients subjected to BIB for 4 months + 1000 kcal/day diet (group B). Results: After 4 months of balloon treatment, the mean weight loss was 13.9 kg and the mean reduction in BMI was 4.8. Weight loss was greater in male patients. Weight loss was accompanied by an improvement of the diseases associated with obesity, in particular diabetes. In the diet vs BIB+diet study, BIB with diet produced a greater weight loss in a shorter time than diet alone. Conclusion: The best indications for BIB were: morbidly obese opatients (BMI>40) and super-obese patients (BMI>50) in preparation for bariatric operations; obese patients with BMI 35-40 with co-morbilities in preparation for bariatric surgery; obese patients with BMI 30-35 with a chronic disease otherwise unresolved; patients with BMI <30 only in a multidisciplinary approach.

Adjustable Gastric Banding: 5-Year Experience

Background: From 1993 to 1999, 172 patients underwent adjustable silicone gastric banding (ASGB) or laparoscopic adjustable silicone gastric banding (LASGB). In 109 patients the adjustable band was placed via laparoscopy; in the other patients it was placed via laparotomy (prelaparoscopic era, conversions from other bariatric operations, conversions for laparoscopic failure). The conversion rate from laparoscopy to laparotomy was 9.3%, occurring in the early part of our experience. Methods: Mean age was 37.9 years, weight 135 ± 14.8 kg (82-218) and BMI 46.3 ± 5.4 (35.1-69.5). All patients had multiple band adjustments, temporary antisecretive, electrolyte and vitamin therapy, and follow-up per routine. Results: Weight loss at 3 years was 30.2%; mean percent loss of excess weight was 62.5%.There was no mortality.The most important technical complications were: gastric pouch dilatation that required band replacement or removal (5.8 %); mild gastric pouch dilatation reversible with adequate dietary and pharmacological treatment (4.6%); intraoperative gastric perforation (2.3%); band migration (0.6%).The band was removed in 2.3%, with conversion to another bariatric procedure in 1.1%. Conclusions: Results have been satisfactory thus far.

Type 2 diabetes and metabolic syndrome are associated with increased expression of 11β-hydroxysteroid dehydrogenase 1 in obese subjects

Objective:The role of glucocorticoids production in adipose tissue in the development of metabolic disorders in humans has not been fully characterized. We investigated whether in obese subjects, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) expression in subcutaneous (SAT) and visceral (VAT) adipose tissue is associated with the occurrence of metabolic disorders and the expression of adiponectin and tumor necrosis factor α (TNFα) and two glucocorticoid-regulated adipokines able to influence the metabolic control.Design and subjects:Sixty-two obese patients were enrolled in the study. SAT and VAT samples were obtained from 13 patients undergoing bariatric surgery (body mass index (BMI) 39.1±5.3 kg/m2). SAT samples were obtained from 49 patients who underwent periumbilical biopsy (BMI 36.9±5.1 kg/m2).Measurements:Oral glucose tolerance tests in subjects without known diabetes. Circulating glucose, lipid, insulin, adiponectin, TNFα and urinary-free cortisol levels. Real-time PCR to quantify mRNA levels of 11β-HSD1, hexose-6-phosphate dehydrogenase (H6PDH), adiponectin and TNFα. Western blot analysis to evaluate 11β-HSD1 protein expression.Results:In the majority of the obese subjects, VAT expresses more 11β-HSD1 than SAT. VAT 11β-HSD1 expression was not associated with metabolic disorders. SAT 11β-HSD1 mRNA levels were higher in subjects with than in those without metabolic syndrome (P<0.05) and in patients with type 2 diabetes compared to patients with impaired or normal glucose tolerance (P<0.0001). SAT 11β-HSD1 expression was independently related to fasting glucose (P<0.0001) and urinary-free cortisol levels (P<0.01), and increased expression of 11β-HSD1 was associated with increased adiponectin and TNFα expression and decreased serum adiponectin levels (all P’s <0.05).Conclusions:In obese subjects, increased 11β-HSD1 expression in SAT, but not in VAT, is associated with the worsening of metabolic conditions. We hypothesize that higher glucocorticoid production in adipose tissue would favor the development of metabolic disorders through a decrease in adiponectin release.

Expression of long pentraxin PTX3 in human adipose tissue and its relation with cardiovascular risk factors

UNLABELLED Pentraxin 3 (PTX3) is an acute phase protein strongly expressed by advanced atherosclerotic lesions. We investigated (a) PTX3 expression and secretion in subcutaneous adipose tissue (SAT) and omental visceral adipose tissue (VAT) obtained from 21 obese (37.4+/-8.15 yr) and 10 normal weight subjects (43.7+/-11.07 yr) and (b) the relationships of adipose PTX3 with tumour necrosis factor alpha (TNFalpha) and adiponectin expression and with cardiometabolic risk factors. Real-time PCR was used to quantify specific mRNA for PTX3, CD68 (macrophage marker), TNFalpha and adiponectin. Fresh adipose tissue was cultured and PTX3 measured in the medium. Serum insulin, glucose, HDL and LDL cholesterol, triglycerides, C-reactive protein (CRP), fibrinogen, adiponectin, TNFalpha and PTX3 were measured. PTX3 expression was similar in the two fat compartments and tended to be higher in obese than in normal weight subjects in VAT only (p=0.05). CD68 and PTX3 expressions were correlated with each other in SAT but not in VAT. After adjustment for age and sex, VAT-PTX3 expression and release were correlated with VAT-TNFalpha expression (p<0.01 for both) and with LDL/HDL ratio (p<0.01 and p<0.001). VAT-PTX3 expression was also correlated with BMI, triglycerides, CRP, fibrinogen and adiponectin (p<0.05 for all). In the multivariate analysis with VAT-PTX3 RNA levels as dependent variable, LDL/HDL ratio and fibrinogen remained independently associated with VAT-PTX3 expression (p<0.01 for both). These associations were not seen within SAT. CONCLUSIONS Human adipose tissue expresses and releases PTX3 likely under TNFalpha control. VAT production of PTX3 seems to contribute to the mechanisms underlying the development of atherosclerosis.

Visceral adipocytes: old actors in obesity and new protagonists in Crohn's disease?

Objective Crohns disease (CD) is a chronic inflammatory bowel disease characterised by a peculiar accumulation of mesenteric adipose tissue covering the inflamed intestinal wall. Methods The authors characterised different adipose tissue compartments of patients with CD using morphological and molecular techniques and compared them to those of subjects with obesity (OB) and healthy subjects with normal weight (N). Adipose tissue samples were taken from subcutaneous adipose tissue, omental visceral adipose tissue (VAT) and healthy mesenteric depot (hMES), as well as from fat wrapping the affected (unhealthy) intestinal tracts (uhMES). Microarray analyses, validated by real-time quantitative PCR technique, were performed in whole adipose tissue and in isolated adipocytes. Results The morphology of subcutaneous adipose tissue was similar in subjects with CD and those with N. In patients with CD, VAT adipocytes were smaller than those derived from uhMES and hMES and were smaller than VAT adipocytes of subjects with N. The molecular profiles of CD, VAT and uhMES were characterised by upregulation of genes related to inflammation and downregulation of those involved in lipid metabolism. Adipocytes isolated from VAT of subjects with CD and those with OB exhibited similar upregulation of genes involved in inflammation and immunity. VAT adipocytes of patients with CD compared to those of patients with OB also showed a greater upregulation of several anti-inflammatory genes. Conclusion In patients with CD, VAT distant from uhMES is affected by inflammation and displays features similar to those of VAT of patients with severe OB. The small diameter of VAT adipocytes of CD, together with their high expression of anti-inflammatory genes, suggests a potentially protective role for this tissue. VAT adipocytes may play an important role in the pathophysiology and/or activity of CD.

Intragastric balloon in obese patients.

Background: Since March 1998, 143 BioEnterics® Intragastric Balloons (BIB) were placed in 132 obese and morbidly obese patients, to study the clinical possibilities of a new system, both from the point of view of the materials used and the application method. Methods: 36 patients were male and 96 female; mean age was 43 years (21-70); mean weight was 115.4 kg (67-229), and mean BMI was 41.0 (29-81). 8 patients were affected by severe respiratory insufficiency. We placed and removed the balloon endoscopically under conscious sedation or general anesthesia. BIB was removed in the majority of patients 4 months after insertion. The patients were given a balanced diet of 800-1000 kcal/day; follow-up involved a monthly check-up (routine blood tests, weight control) and a visit every 15 days with the dietitian. Results: Mean weight loss was 14.4 kg; mean reduction in BMI was 5.2.Weight loss was much better in males. The weight loss produced an improvement of the complications associated with the obesity. Complications observed were: balloon intolerance (9 early removals), 1 balloon deflated and passed, 2 cases of gastric ulcer at balloon removal. Conclusions:The most correct indications for BIB should be: extremely obese patients (BMI>40) in preparation for a bariatric operation; obese patients with BMI 30-35 with a chronic disease otherwise unresolved; patients with BMI< 30 in a multidisciplinary approach.

Cholesterol Metabolism After Bariatric Surgery in Grade 3 Obesity: Differences between malabsorptive and restrictive procedures

OBJECTIVE Malabsorptive bariatric surgery (biliopancreatic diversion and biliointestinal bypass [BIBP]) reduces serum cholesterol levels more than restrictive surgery (adjustable gastric banding [AGB]), and this is thought to be due to greater weight loss. Our aim was to evaluate the changes of cholesterol metabolism induced by malabsorptive and restrictive surgery independent of weight loss. RESEARCH DESIGN AND METHODS In a nonrandomized, self-selected, unblinded, active-comparator, bicenter, 6-month study, glucose metabolism (blood glucose and serum insulin levels and homeostasis model assessment of insulin resistance [HOMA-IR] index) and cholesterol metabolism (absorption: serum campesterol and sitosterol levels; synthesis: serum lathosterol levels; catabolism: rate of appearance and serum concentrations of serum 7-α- and serum 27-OH-cholesterol after infusions of deuterated 7-α- and 27-OH-cholesterol in sequence) were assessed in grade 3 obesity subjects undergoing BIBP (n = 10) and AGB (n = 10). Evaluations were performed before and 6 months after surgery. RESULTS Subjects had similar values at baseline. Weight loss was similar in the two groups of subjects, and blood glucose, insulin levels, HOMA-IR, and triglycerides decreased in a similar way. In contrast, serum cholesterol, LDL cholesterol, non-HDL cholesterol, serum sitosterol, and campesterol levels decreased and lathosterol levels increased only in BIBP subjects, not in AGB subjects. A significant increase in 7-α-OH-cholesterol occurred only with BIBP; serum 27-OH-cholesterol decreased in both groups. CONCLUSIONS Malabsorptive surgery specifically affects cholesterol levels, independent of weight loss and independent of glucose metabolism and insulin resistance. Decreased sterol absorption leads to decreased cholesterol and LDL cholesterol levels, accompanied by enhanced cholesterol synthesis and enhanced cholesterol catabolism. Compared with AGB, BIBP provides greater cholesterol lowering.

Biliary pancreatic diversion and laparoscopic adjustable gastric banding in morbid obesity: their long-term effects on metabolic syndrome and on cardiovascular parameters

BackgroundBariatric surgery is able to improve glucose and lipid metabolism, and cardiovascular function in morbid obesity. Aim of this study was to compare the long-term effects of malabsorptive (biliary pancreatic diversion, BPD), and restrictive (laparoscopic gastric banding, LAGB) procedures on metabolic and cardiovascular parameters, as well as on metabolic syndrome in morbidly obese patients.Methods170 patients studied between 1989 and 2001 were called back after a mean period of 65 months. 138 patients undergoing BPD (n = 23) or LAGB (n = 78), and control patients (refusing surgery and treated with diet, n = 37) were analysed for body mass index (BMI), blood glucose, cholesterol, and triglycerides, blood pressure, heart rate, and ECG indexes (QTc, Cornell voltage-duration product, and rate-pressure-product).ResultsAfter a mean 65 months period, surgery was more effective than diet on all items under evaluation; diabetes, hypertension, and metabolic syndrome disappeared more in surgery than in control patients, and new cases appeared only in controls. BPD was more effective than LAGB on BMI, on almost all cardiovascular parameters, and on cholesterol, not on triglyceride and blood glucose. Disappearance of diabetes, hypertension, and metabolic syndrome was similar with BPD and with LAGB, and no new cases were observed.ConclusionThese data indicate that BPD, likely due to a greater BMI decrease, is more effective than LAGB in improving cardiovascular parameters, and similar to LAGB on metabolic parameters, in obese patients. The greater effect on cholesterol levels is probably due to the different mechanism of action.

Prevention of Pouch Dilatation after Laparoscopic Adjustable Gastric Banding

Background: The major long-term complication of laparoscopic adjustable gastric banding (LAGB) is dilatation of the gastric pouch, that is reported with a frequency ranging from 1 to 25%, and often requires removal of the band. In addition to the usual recommendations of bariatric surgery centers and dietetic advice to prevent this complication, over the last 4 years we introduced a technical modification of the procedure. Methods: From Nov 1993 to Dec 2004, 684 morbidly obese patients underwent adjustable gastric banding, 83 patients by open surgery and 601 patients by laparoscopy. The first 323 patients (group A) were operated by the perigastric approach, and 57 patients (group B) were operated by the pars flaccida approach. Since Dec 2000, 304 patients (group C) were operated with a modified pars flaccida technique, which consisted in suturing the gastric lesser curvature below the band with one or two stitches to the right phrenic crus to secure the band in place. Results: In group A, the most important late complication was irreversible dilatation of the gastric pouch, which occurred in 35 patients (10.8%), and required removal of the band in 30 cases and replacement in 5. In group B, there were 3 pouch dilatations (5.2%). In group C, only 4 dilatations occurred (1.31%), which required 3 band removals and 1 band replacement. Conclusion: Dilatation of the gastric pouch appears to be dramatically reduced by our minor technical modification of band placement.

Differences in Visceral Fat and Fat Bacterial Colonization between Ulcerative Colitis and Crohn’s Disease. An In Vivo and In Vitro Study

Crohn’s disease (CD) is notably characterized by the expansion of visceral fat with small adipocytes expressing a high proportion of anti-inflammatory genes. Conversely, visceral fat depots in ulcerative colitis (UC) patients have never been characterized. Our study aims were a) to compare adipocyte morphology and gene expression profile and bacterial translocation in omental (OM) and mesenteric (MES) adipose tissue of patients with UC and CD, and b) to investigate the effect of bacterial infection on adipocyte proliferation in vitro. Specimens of OM and MES were collected from 11 UC and 11 CD patients, processed and examined by light microscopy. Gene expression profiles were evaluated in adipocytes isolated from visceral adipose tissue using microarray and RTqPCR validations. Bacteria within adipose tissue were immuno-detected by confocal scanning laser microscopy. Adipocytes were incubated with Enterococcus faecalis and cells counted after 24h. Morphology and molecular profile of OM and MES revealed that UC adipose tissue is less inflamed than CD adipose tissue. Genes linked to inflammation, bacterial response, chemotaxis and angiogenesis were down-regulated in adipocytes from UC compared to CD, whereas genes related to metallothioneins, apoptosis pathways and growth factor binding were up-regulated. A dense perinuclear positivity for Enterococcus faecalis was detected in visceral adipocytes from CD, whereas positivity was weak in UC. In vitro bacterial infection was associated with a five-fold increase in the proliferation rate of OM preadipocytes. Compared to UC, visceral adipose tissue from CD is more inflamed and more colonized by intestinal bacteria, which increase adipocyte proliferation. The influence of bacteria stored within adipocytes on the clinical course of IBD warrants further investigations.