Marco Antonio Zappa

Lap Band adjustable gastric banding system: the Italian experience with 1863 patients operated on 6 years.

Background: The Lap Band system procedure is currently the most common bariatric surgical procedure worldwide. This is an interim report of the experience of the 27 Italian centers participating in the national collaborative study group for Lap Band® (GILB). Methods: An electronic database was specifically created. It was mailed and e-mailed to all of the surgeons now performing the laparoscopic gastric banding operation in Italy. Results: Beginning in January 1996, 1893 patients were recruited for the study. There were 1534 women and 359 men with a mean body mass index (BMI) of (range 30.4–83.6) and a mean age of 37.8 ± 10.9 years (range; 17–74). The mortality rate has been 0.53% (n = 10), mainly due to cardiovascular complications (myocardial infarction, pulmonary embolism). The laparotomic conversion rate has been 3.1% (59/1893) and was higher in superobese patients (BMI>50) than in to morbidly obese patients (BMI <50) (p <0.05). Postoperative complications occurred in 193 patients (10.2%), including tube port failure (n = 79; 40.9%), gastric pouch dilation (GPD) (n = 93; 48.9%), and gastric erosion (n = 21, 10.8%). Most GPD (65.5%) occurred during the first 50 patients treated at each center. The incidence of GPD decreased as the surgeons acquired more experience. Surgery for complications was often performed by laparoscopic access, rarely via laparotomy. No death was recorded as a consequence of surgery to treat complications. Weight loss has been evaluated at the following intervals: 6, 12, 24, 36, 48, 60, and 72 months, with BMI 37.9, 33.7, 34.8, 34.1, 32.7, 34.8, and 32. Conclusions: The Lap Band system procedure has a very low mortality rate and a low morbidity rate and it yields satisfactory weight loss. Surgery for complications can be performed safely via laparoscopic access.

Effects of the Beach Chair Position, Positive End-expiratory Pressure, and Pneumoperitoneum on Respiratory Function in Morbidly Obese Patients during Anesthesia and Paralysis

Background:The authors studied the effects of the beach chair (BC) position, 10 cm H2O positive end-expiratory pressure (PEEP), and pneumoperitoneum on respiratory function in morbidly obese patients undergoing laparoscopic gastric banding. Methods:The authors studied 20 patients (body mass index 42 ± 5 kg/m2) during the supine and BC positions, before and after pneumoperitoneum was instituted (13.6 ± 1.2 mmHg). PEEP was applied during each combination of position and pneumoperitoneum. The authors measured elastance (E,rs) of the respiratory system, end-expiratory lung volume (helium technique), and arterial oxygen tension. Pressure–volume curves were also taken (occlusion technique). Patients were paralyzed during total intravenous anesthesia. Tidal volume (10.5 ± 1 ml/kg ideal body weight) and respiratory rate (11 ± 1 breaths/min) were kept constant throughout. Results:In the supine position, respiratory function was abnormal: E,rs was 21.71 ± 5.26 cm H2O/l, and end-expiratory lung volume was 0.46 ± 0.1 l. Both the BC position and PEEP improved E,rs (P < 0.01). End-expiratory lung volume almost doubled (0.83 ± 0.3 and 0.85 ± 0.3 l, BC and PEEP, respectively; P < 0.01 vs. supine zero end-expiratory pressure), with no evidence of lung recruitment (0.04 ± 0.1 l in the supine and 0.07 ± 0.2 in the BC position). PEEP was associated with higher airway pressures than the BC position (22.1 ± 2.01 vs. 13.8 ± 1.8 cm H2O; P < 0.01). Pneumoperitoneum further worsened E,rs (31.59 ± 6.73; P < 0.01) and end-expiratory lung volume (0.35 ± 0.1 l; P < 0.01). Changes of lung volume correlated with changes of oxygenation (linear regression, R2 = 0.524, P < 0.001) so that during pneumoperitoneum, only the combination of the BC position and PEEP improved oxygenation. Conclusions:The BC position and PEEP counteracted the major derangements of respiratory function produced by anesthesia and paralysis. During pneumoperitoneum, only the combination of the two maneuvers improved oxygenation.

INCREASED EXPRESSION AND ACTIVITY OF THE TRANSCRIPTION FACTOR FOXO1 IN NONALCOHOLIC STEATOHEPATITIS

OBJECTIVE—Nonalcoholic fatty liver, affecting 34% of the U.S. population, is characterized by hepatic insulin resistance, which is more marked in the presence of steatohepatitis, and frequently precedes hyperglycemia. The molecular mechanisms underlying the relationship between fatty liver and insulin resistance are still undergoing definition and have not been evaluated in humans. Our aim was to evaluate the relationship between insulin resistance and the expression and regulation of forkhead box–containing protein O subfamily-1 (FOXO1), a transcription factor that mediates the effect of insulin on the gluconeogenic genes PEPCK and glucose-6-phosphatase catalytic subunit (G6PC). RESEARCH DESIGN AND METHODS—FOXO1, PEPCK, and G6PC mRNA levels were evaluated in 84 subjects: 26 with steatohepatitis, 28 with steatosis alone, 14 with normal liver histology without metabolic alterations, and 16 with hepatitis C virus chronic hepatitis, of whom 8 were with and 8 were without steatosis. Protein expression and regulation of FOXO1 and upstream insulin signaling were analyzed in a subset. RESULTS—Expression of PEPCK was higher in steatohepatitis compared with steatosis alone and normal liver, and it was correlated with the homeostasis model assessment of insulin resistance (HOMA-IR) index. FOXO1 mRNA levels were higher in steatohepatitis, correlated with PEPCK and G6PC mRNA and with HOMA-IR. FOXO1 upregulation was confirmed at protein levels in steatohepatitis and, in the presence of oxidative stress, was associated with decreased Ser256 phosphorylation, decreased Akt1, and increased Jun NH2-terminal kinase-1 activity. Consistently, immunohistochemistry showed increased FOXO1 expression and nuclear localization in steatohepatitis. FOXO1 mRNA levels correlated with nonalcoholic steatohepatitis activity score and were modulated by drugs counteracting hepatic lipogenesis. CONCLUSIONS—FOXO1 expression and activity are increased in patients with steatohepatitis, and mRNA levels are correlated with hepatic insulin resistance.

Genetic variants regulating insulin receptor signalling are associated with the severity of liver damage in patients with non-alcoholic fatty liver disease

Background/aims The aim of this study was to assess the effect of functional ENPP1(ectoenzyme nucleotide pyrophosphate phosphodiesterase 1)/PC-1 (plasma cell antigen-1) and IRS-1 (insulin receptor substrate-1) polymorphisms influencing insulin receptor activity on liver damage in non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome, whose progression is associated with the severity of insulin resistance. Patients and methods 702 patients with biopsy-proven NAFLD from Italy and the UK, and 310 healthy controls. The Lys121Gln ENPP1/PC-1 and the Gly972Arg IRS-1 polymorphisms were evaluated by restriction analysis. Fibrosis was evaluated according to Kleiner. Insulin signalling activity was evaluated by measuring phosphoAKT levels by western blotting in a subset of obese non-diabetic patients. Results The ENPP1 121Gln and IRS-1 972Arg polymorphisms were detected in 28.7% and 18.1% of patients and associated with increased body weight/dyslipidaemia and diabetes risk, respectively. The ENPP1 121Gln allele was significantly associated with increased prevalence of fibrosis stage >1 and >2, which was higher in subjects also positive for the 972Arg IRS-1 polymorphism. At multivariate analysis, the presence of the ENPP1 121Gln and IRS-1 972Arg polymorphisms was independently associated with fibrosis >1 (OR 1.55, 95% CI 1.24 to 1.97; and OR 1.57, 95% CI 1.12 to 2.23, respectively). Both polymorphisms were associated with a marked reduction of ∼70% of AKT activation status, reflecting insulin resistance and disease severity, in obese patients with NAFLD. Conclusions The ENPP1 121Gln and IRS-1 972Arg polymorphisms affecting insulin receptor activity predispose to liver damage and decrease hepatic insulin signalling in patients with NAFLD. Defective insulin signalling may play a causal role in the progression of liver damage in NAFLD.

Italian Group for Lap-Band System®: Results of Multicenter Study on Patients with BMI ≤35 kg/m2

Background: The Lap-Band System® is the most common bariatric operation world-wide. Current selection criteria do not include patients with BMI ≤ 35. We report the Italian multicentre experience with BMI ≤ 35 kg/m2 over the last 5 years. Patients and Methods: Data were obtained from 27 centres involved in the Italian Collaborative Study Group for Lap-Band System®. Detailed information was collected on a specially created electronic data sheet (MS Access 2000) on patients operated in Italy since January 1996. Items regarding patients with BMI ≤ 35 were selected. Data were expressed as mean ± SD except as otherwise indicated. Results: 225 (6.8%) out of 3,319 Lap-Band® patients were recruited from the data-base. 15 patients, previously submitted to another bariatric procedure (BIB =14; VBG= 1) were excluded. 210 patients were eligible for study (34M/176F, mean age 38.19±11.8, range 17-66 years, mean BMI 33.9±1.1, range 25.1-35 kg/m2, mean excess weight 29.5±7.1, range 8-41). 199 comorbidities were diagnosed preoperatively in 55/210 patients (26.2%). 1 patient (0.4%) (35 F) died 20 months postoperatively from sepsis following perforation of dilated gastric pouch. There were no conversions to laparotomy. Postoperative complications presented in 17/210 patients (8.1%). Follow-up was obtained at 6, 12, 24, 36, 48 and 60 months. At these time periods, mean BMI was 31.1±2.15, 29.7±2.19, 28.7±3.8, 26.7±4.3, 27.9±3.2, and 28.2±0.9 kg/m2 respectively. Co-morbidities completely resolved 1 year postoperatively in 49/55 patients (89.1%). At 60 months follow-up, only 1 patient (0.4%) has a BMI >30. Conclusions: Although surgical indications for BMI ≤ 35 remain questionable, the Lap-Band® in this study demonstrated that all but 1 patient achieved normal weight, and most lost their co-morbidities with a very low mortality rate.

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.

The APOC3 T-455C and C-482T promoter region polymorphisms are not associated with the severity of liver damage independently of PNPLA3 I148M genotype in patients with nonalcoholic fatty liver

BACKGROUND & AIMS The T-455C and C-482T APOC3 promoter region polymorphisms (SNPs) have recently been reported to predispose to dyslipidemia, insulin resistance, and nonalcoholic fatty liver disease (NAFLD) in Indian subjects, but the association with liver damage has not been evaluated so far. The aim was to assess the association between APOC3 SNPs and liver damage in Caucasian patients. METHODS We considered 437 Italian patients with histological diagnosis of NAFLD (including 137 children, 120 morbid obese) and 316 healthy controls, 71 Italian family trios, and 321 patients from the UK. APOC3 SNPs were determined by sequencing, allele-specific oligonucleotide probes and PCR-restriction fragment length polymorphism analysis, hepatic APOC3 mRNA levels by real-time PCR. RESULTS APOC3 SNPs were not associated with NAFLD in Italian subjects, although a borderline significance for the transmission of the -455T allele was observed in the family study. Homozygosity for the APOC3 wild-type genotype (APOC3 WT) was associated with a more favorable lipid profile in control subjects, and consistently with lower hepatic APOC3 mRNA levels in obese patients without diabetes. However, APOC3 SNPs, alone or in combination, were not associated with insulin resistance, altered lipid levels, liver enzymes, and with liver damage (severity of steatosis, nonalcoholic steatohepatitis, and moderate/severe fibrosis) in Italian as well as in UK patients, and in the whole cohort. Stratification for the I148M PNPLA3 mutation, associated with the susceptibility to NASH, did not alter the results. CONCLUSIONS APOC3 genotype is not associated with progressive liver damage in Caucasian patients with NAFLD.

Bariatric Surgery: Cost-Effectiveness and Budget Impact

Bariatric surgery is to date the most effective treatment for morbid obesity and it has been proven to reduce obesity-related comorbidities and total mortality. As any medical treatment, bariatric surgery is costly and doubts about its affordability have been raised. On the other hand, bariatric surgery may reduce the direct and indirect costs of obesity and related comorbidities. The appreciation of the final balance between financial investments and savings is critical from a health economic perspective. In this paper, we try to provide a brief updated review of the most recent studies on the cost-efficacy of bariatric surgery, with particular emphasis on budget analysis. A brief overview of the economic costs of obesity will also be provided. The epidemic of obesity may cause a significant reduction in life expectancy and overwhelming direct and indirect costs for citizens and societies. Cost-efficacy analyses included in this review consistently demonstrated that the additional years of lives gained through bariatric surgery may be obtained at a reasonable and affordable cost. In groups of patients with very high obesity-related health costs, like patients with type 2 diabetes, the use of bariatric surgery required an initial economic investment, but may save money in a relatively short period of time.

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.

Results of the Italian Multicenter Study on 239 Super-obese Patients Treated by Adjustable Gastric Banding

Background: Laparoscopic adjustable gastric banding (LAGB) is the most common bariatric operation. This study is a retrospective analysis of the multicenter Italian experience in patients with BMI >50 over the last 4 years. Methods: An electronic data sheet made for LAGBoperated patients since January 1996, was mailed and e-mailed to all surgeons involved in this kind of procedure in Italy. Items regarding patients with BMI >50 were selected. Analysis used Fishers exact test and logarithmic regression analysis (P<0.05 significant). Data were expressed as mean ± SD. Results: 239 patients (13.3%), out of 1,797 LapBand® operated patients entered the study (179F / 60M), with mean age 37.6±11.3 years (19-69) and mean BMI 54.6±4.8 (50.1-83.6). Laparotomic conversion rate was 5.4% (44/239). Postoperative complications occurred in 24 / 239 patients (9.0%). Follow-up was obtained in 218 / 218, 198 / 198, 121 / 147, 75 / 93, 30 / 38 LAGB patients at 6, 12, 24, 36, and 48 months respectively. At these time periods, mean BMI was 46.7, 43.9, 42.2, 41.9, and 39.3 kg/m2. At the same intervals, mean %EWL was 24.1, 34.1, 38.8, 38.9, and 52.9%.The number of patients with <25% EWL at 12, 24, 36, and 48 months follow-up were 34, 10, 4, and 0. Serious co-morbidities (189 in 124 of 239, 57%) had completely resolved 1 year postoperatively in 74 / 124 of the patients (59.6%). Conclusion: Although super-obese patients following the LAGB remain obese with BMI >35, in the short-term most lose their co-morbidities, with a very low morbidity and mortality rate.