ΒΑΡΙΑΤΡΙΚΗ ΧΕΙΡΟΥΡΓΙΚΗ Αλήθειες, Υπερβολές και Ανακρίβειες ΝΙΚΟΛΑΟΣ Λ. ΚΑΤΣΙΛΑΜΠΡΟΣ

ΒΑΡΙΑΤΡΙΚΗ ΧΕΙΡΟΥΡΓΙΚΗ Αλήθειες, Υπερβολές και Ανακρίβειες ΝΙΚΟΛΑΟΣ Λ. ΚΑΤΣΙΛΑΜΠΡΟΣ

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Από: Schneider BE et al, Diabetes Care 2005; 28: 475-480 ΚΡΙΤΗΡΙΑ ΓΙΑ ΒΑΡΙΑΤΡΙΚΗ ΧΕΙΡΟΥΡΓΙΚΗ ΒΜΙ 40 kg/m 2 ή ΒΜΙ 35 kg/m 2 με σημαντικές συνυπάρχουσες νοσηρές καταστάσεις σχετιζόμενες με την παχυσαρκία Ηλικία μεταξύ 16 και 65 ετών Αποδεκτοί χειρουργικοί κίνδυνοι Στοιχειοθετημένη αποτυχία μη χειρουργικών προσεγγίσεων για μακροχρόνια απώλεια βάρους Ψυχολογικά ισορροπημένος ασθενής με ρεαλιστικές προσδοκίες Ασθενής με επαρκή πληροφόρηση και κίνητρα Δέσμευση για παρατεταμένες μεταβολές του τρόπου ζωής Επίλυση προβλημάτων καταχρήσεως ουσιών ή οινοπνεύματος Απουσία ενεργού σχιζοφρένειας και μη θεραπευομένης σοβαρής καταθλίψεως

Mean Percent Weight Change during a 15-Year Period in the Control Group and the Surgery Group,According to the Method of Bariatric Surgery. Sjöström L et al. N Engl J Med 2007; 357:741-52.

n engl j med 357;8 www.nejm.org august 23, 2007 (MORTALITY, SOS STUDY)

Ενδείξεις βαριατρικής επέμβασης σε άτομα με ΣΔ τύπου 2. Ενδείξεις ΒΜΙ >35 Σχετικά πρόσφατη έναρξη ΣΔ (<5 έτη) Νέα άτομα (<60 ετών) Αποδεκτός χειρουργικός κίνδυνος Υψηλό κίνητρο. Αποτυχημένες προσπάθειες απώλειας με συντηρητικό τρόπο. Αντενδείξεις Στεφανιαία νόσος Αλκοολισμός ή διατροφικές διαταραχές Εγκατεστημένη νεφροπάθεια Έλλειψη κινήτρου και κοινωνικής υποστήριξης

Πιθανοί νευροενδοκρινικοί μηχανισμοί υποστροφής του ΣΔ Μετά από βαριατρική επέμβαση γαστρικής παράκαμψης Υπόθεση άπω ΓΕΣ Η γρήγορη διέλευση της τροφής λόγω παράκαμψης τμήματος του γαστρεντερικού σωλήνα οδηγεί σε διέγερση L κυττάρων, με αποτέλεσμα την αυξημένη έκκριση ινσουλινοεκκριτικών ορμονών (GLP-1) (Φαινόμενο ινκρετίνης) Υπόθεση εγγύς ΓΕΣ Η παράκαμψη τμήματος του εγγύς τμήματος γαστρεντερικού σωλήνα κατά τη διέλευση της τροφής έχει ως αποτέλεσμα αποφυγή έκκρισης παραγόντων που ελαττώνουν την έκκριση της ινσουλίνης ή προάγουν την ινσουλινοαντίσταση (Φαινόμενο αντι-ινκρετίνης)

Multiple Actions of GLP-1 Act to Reduce Hyperglycaemia GLP-1 has multiple actions that reduce hyperglycaemia, including: Glucose-dependent stimulation of insulin secretion Glucose-dependent suppression of glucagon secretion Slowing of gastric emptying Improvement in β-cell function Increase in β-cell mass, function, and islet neogenesis (animal studies) In addition, GLP-1 has been associated with reduced food intake and reductions in body weight Drucker DJ. Diabetes Care. 2003;26:2929-2940.

Removal of Duodenum Elicits GLP-1 Secretion, Muscogiouri G et al, Diabetes Care, June 2013, vol 36 : 1641-1643 GLP1

Όμως πολλοί παράγοντες παρεμβαίνουν

Mingrone G et al. Bariatric surgery versus conventional medical therapy for type 2 diabetes. N Engl J Med 2012 Mar 26 (e-pub ahead of print) Randomized, controlled, single-center clinical trial (Catholic University, Rome) N=60 severely obese patients with T2DM and BMI more than 35 Conventional medical therapy vs. bariatric surgery (Gastric Bypass or Biliop. Diversion) Primary endpoint: diabetes remission at 2 years (fasting glucose <100 + HbA1c <6.5%) Outcome parameters Medical Therapy (N=18) Gastric Bypass (N=19) Biliopancreatic Diversion (N=19) Diabetes remission at 2 years (%) 0 75 (p<0.001) 95 (p<0.001) HbA1 average values at 2 years (%) 7.7 ± 0.6 6.4 ± 1.4* (p=0.003) 5.0 ± 0.5* (p<0.001) Weight loss (%) 4.7 ± 6.4*p=0.001 for Gastric Bypass vs. Biliopancreatic Diversion 33.3 ± 7.9 (p<0.001) 33.8 ± 10.2 (p<0.001) Preoperative BMI and weight loss did not predict the improvement in hyperglycemia after these procedures

Schauer PR et al. Bariatric surgery versus intensive medical therapy in obese patients with diabetes. N Engl J Med 2012 Mar 26 (e-pub ahead of print) Randomized, controlled, single-center clinical trial (Cleveland Clinic, Boston) N=150 obese patients with uncontrolled T2DM Intensive medical therapy vs. medical therapy + bariatric surgery (RYGB/Sleeve Gastrectomy) Primary endpoint: HbA1c 6% at 12 months Outcome parameters % of patients with final HbA1c 6% HbA1c mean values at 12 months (%) Medical Therapy (N=41) 12 7.5 ± 1.8 Weight loss (Kg) 5.4 ± 8 Gastric Bypass (N=50) 42 (p=0.002) 6.4 ± 0.9 (p<0.001) 29.4 ± 9* (p<0.001) Sleeve Gastrectomy (N=49) 37 (p=0.008) 6.6 ± 1.0 (p=0.003) 25.1 ± 8.5* (p<0.001) *p=0.02 for Gastric Bypass vs. Sleeve Gastrectomy

DM 2 and Bariatric Surgery DM 2 Meta-analysis: 1990-2006 621 studies, 98656 patients 78.1% Complete resolution BPD/Duodenal switch 95.1% RYGB 80.3% Gastroplasty 79.7% Adj.gastric banding 56.7% Buchwald et al. Am J Med 2009; 122: 248-56

Αποτελεσματικότητα RYGB στον ΣΔ2 ανάλογα με το είδος της θεραπείας (Ύφεση στον ένα χρόνο) Δίαιτα μόνο 89.8% Δισκία 82.7% Ινσουλίνη 53.3% Carbonell A Surg Obes Relat Dis 2008; 4: 441-444 Επιπλέον: Διάρκεια διαβήτη Προεγχειρητικό C-πεπτίδιο Ηλικία (καλύτερα στους μεγαλύτερους) Για ΒΜΙ > 50: Duodenal switch: 100% RYGB: 60%

Όμως η αλήθεια έχει και άλλη όψη Overall, 68.2 % (95 % confidence interval [CI], 66 and 70 %) experienced an initial complete diabetes remission within 5 years after surgery. Among these, 35.1 % (95 % CI, 32 and 38 %) redeveloped diabetes within 5 years. The median duration of remission was 8.3 years. Significant predictors of complete remission and relapse were poor preoperative glycemic control, insulin use, and longer diabetes duration. Άρα αρχικά 1/3 όχι ανταπόκριση και στο 1/3 αυτών που αρχικά παρουσίασαν ύφεση του ΣΔ σημειώθηκε υποτροπή

Bariatric Surgery and Prevention of Type 2 Diabetes in Swedish Obese Subjects NEJM, Aug 23, 2012, Carlsson LMS et al

ΜΕΙΩΣΗ ΕΠΙΠΛΟΚΩΝ ΤΟΥ ΣΔ

Υποχώρηση ΣΔ2 μετά τη βαριατρική επέμβαση ανάλογα με τον χρόνο παρακολούθησης Έτη παρακολούθησης Είδος επέμβασης 1-2 3-6 7-10 - Κάθετη γαστροπλαστική 50-72 25-65 - Δακτύλιος στομάχου 29-87 45-72 14-60 - Επιμήκης γαστρεκτομή (sleeve) 33-58 66 - Roux-en-Y γαστρική παράκαμψη 48-85 53-77 25-68 - Χολοπαγκρεατική εκτροπή 65-83 62-81 60-80 AACE Bariatric surgery guidelines. Endocr Pract 2008; 14 (Suppl.1): 1-83

Restoration of Euglycemia and Normal Acute Insulin Response to Glucose in Obese Subjects With Type 2 Diabetes Following Bariatric Surgery Eftihia V. Polyzogopoulou,1 Fotios Kalfarentzos,2 Apostolos G. Vagenakis,1 and Theodore K. Alexandrides1 Diabetes 52 : 1098-1103, 2003

Cumulative incidence of fatal and total cardiovascular events (myocardial infarction + stroke) in the control and surgery groups of the Swedish Obese Subjects study. LARS SJÖSTRÖM, 20 Sept 2012

Βαριατρική χειρουργική και υπέρταση (α) 40-70% των χειρουργηθέντων έχουν ΥΠΕΡΤΑΣΗ Μελέτη SOS VBG: 8 χρόνια μετά ΟΧΙ ΣΗΜΑΝΤΙΚΗ ΔΙΑΦΟΡΑ RYGB: ΑΠ Άλλες μελέτες: AGB (Δακτύλιος) SG (Επιμ. γαστρ/μή) RYGB (Γαστρική παρ/μψη) DS (12λική εκτροπή) [superobese] Εξάλειψη υπερτάσεως 48-63% 78-94% 65-91% > 68%

Βαριατρική χειρουργική και υπέρταση (β) Νορμοτασικά άτομα Συστολική ΑΠ Διαστολική ΑΠ Όχι μεταβολή Μικρή, προοδευτική μείωση Άτομα με έλλειψη βιτ D: μειωμένη ανταπόκριση Εάν χορηγηθεί βιτ D: σαφής βελτίωση (75% έναντι 32%) Am J Surg 2008;195:349-352

Weight loss after bariatric surgery improves aortic elastic properties and left ventricular function in individuals with morbid obesity: a 3- year follow-up study Ignatios Ikonomidis et al, J Hypertens 25:439 447 Q 2007 Conclusion Weight reduction after bariatric surgery normalizes aortic function, reduces left ventricular hypertrophy and, thus, improves left ventricular diastolic function in morbidly obese individuals over a 3-year period of follow-up.

Βαριατρική χειρουργική και λιπίδια Μελέτη SOS Δεκαετής παρακολούθηση Τα ποσοστά βελτιώσεως ποικίλλουν αλλά είναι σχετικά μικρά AGB (Δακτύλιος) VBG (Γαστροπλαστική) TG (%) 18 15 28 TC (%) 5 5 12.6 HDL-C (%) 20.4 23.5 47.5 * RYGB και BPD: Δυσαπορρόφηση RYGB* (Παράκαμψη)

GASTRIC BYPASS INDUCES A MORE PRONOUNCED IMPROVEMENT IN POSTPRANDIAL GLUCOSE AND TRIGLYCERIDE LEVELS THAN SLEEVE GASTRECTOMY Alexander Kokkinos, Kleopatra Alexiadou, Nicholas Tentolouris, Nicholas Katsilambros First Department of Propaedeutic Medicine, Athens University Medical School, Laiko General Hospital, Athens, Greece EASD Nutrition Study Group Meeting Rome 2011

SUBJECTS AND METHODS 22 non-diabetic patients who underwent either Rouxen-Y Gastric Bypass (GB, n=9) or Sleeve Gastrectomy (SG, n=13) were consecutively recruited Anthropometric measurements: Weight, Height, BMI, Waist and Hip circumference, Waist-to-Hip ratio (WHR) Test meal consisting of 200 ml ice cream (450 kcal, 59% fat, 33% CHO, 8% protein) Blood sampling before meal and 30, 60, 90, 120, 150, 180 postprandially

SUBJECTS AND METHODS (2) Measurement of glucose and triglycerides at all time points Comparison between groups at each specific time point (t-test) and in terms of Area Under the Curve (AUC) using the trapezoid rule Assessment before and 3 months after surgery

RESULTS (3) AREA UNDER THE CURVE (DIVIDED BY TIME) COMPARISONS GB Glucose Preop Postop P Preop Postop P P between GB + SG 104.6 ± 6.3 93.8 ± 12.5 0.08 124.5 ± 47.5 SG 101.0 ± 8.7 Triglycerides Preop Postop P Preop Postop P P between GB + SG 122.8 ± 45.6 109.0 ± 26.6 NS 143.2 31 ± 26.5 144.4 ± 38.6 NS NS NS 0.03

Βαριατρική χειρουργική και καρδιακή ανεπάρκεια Καρδιακή παροχή Παχυσαρκία Κυκλοφ. όγκος αίματος Μάζα αρ. κοιλίας Διαστάσεις αρ. κοιλίας ΥΠΟΘΕΣΗ: Δίαιτα ή εγχείρηση Βελτίωση Cardiol Rev 2011;19: 1-4

Βαριατρική χειρουργική και στεφανιαία νόσος Βελτίωση περιφερικής αγγειοδιασταλτικής λειτουργίας QT διαστήματος ( σε νοσογόνο παχυσαρκία) μετά από BPD Nutr Metab Cardiovasc Dis 2010 Obesity 2007; 1448-1454

Arterial baroreflex sensitivity (BRS) in lean and obese women after glucose ingestion 30 25 BRS (ms/mmhg) 20 15 10 5 0 P for interaction = 0.003* 0 60 120 Time after glucose load Lean Obese * ANOVA for repeated measures M. Horianopoulou, S. Liatis, D. Perea, N. Tsokos, A. Petsas, I. Skrapari, C. Tsigos, N. Katsilambros Obes Rev 2005;6(Suppl 1):67

Effect of weight loss on baroreflex sensitivity of women with morbid obesity. 60 Skrapari I, Tentolouris N, Perrea D, Bakoyiannis C, Papazafiropoulou A, Katsilambros N Obesity (Silver Spring). 2007 Jul;15(7):1685-93 50 40 30 20 19.87 10 8.97 0-10 BRS prior to gastric bypass (mean BMI=49.08) BRS 2 months post gastric bypass (mean BMI=37.88)

OBES SURG (2013) 23:31 38 DOI 10.1007/s11695-012-0743-8 Baroreceptor Sensitivity and Heart Rate Variability Improvement in Cardiovascular Indices After Roux-en-Y Gastric Bypass or Sleeve Gastrectomy for Morbid Obesity Alexander Kokkinos & Kleopatra Alexiadou & Christos Liaskos & Georgia Argyrakopoulou & Ioanna Balla & Nicholas Tentolouris & Ioannis Moyssakis & Nicholas Katsilambros & Irene Vafiadis & Andreas Alexandrou & Theodoros Diamantis

Multiple factors are involved in post-surgical bone mass loss including nutritional deficiencies, rapid weight loss, as well as possible effects of changes in circulating concentrations of fat derived adipokines and gut-derived appetite-regulatory hormones. However, the roles of adipokines and gut hormones in skeletal regulation, as well as the mechanisms by which they work, are not yet fully defined.

(Pellitero S et al)

Pregnancy after bariatric surgery does not affect weight loss Alatishe A et al BMJ 2012;345:e6293 Twenty one women became pregnant after surgery. They were significantly younger at the time of surgery than the remaining women but were well matched for preoperative weight, BMI, and bariatric procedure. The median interval between bariatric surgery and first pregnancy was 11 months (range 1.5-36); pregnancy was planned in six women. Eighteen women completed pregnancy successfully, 12 by vaginal delivery and six by caesarean section; two undertook medical termination and one had a spontaneous miscarriage. The pregnancy group lost 70.4% of excess weight compared with 70.0% in the nonpregnancy group at a median 30 months after surgery. We conclude that pregnancy after bariatric surgery in women of childbearing age is safe and does not adversely influence weight loss outcomes. However, close surveillance of maternal weight and nutritional status is advisable, particularly if conception occurs in the first year after surgery.

Metabolic surgery and obstructive sleep apnoea: the protective effects of bariatric procedures Ashrafian H, thorax.bmj.com on November 26, 2012 Review A literature analysis was performed with statistical pooling of available surgical and medical studies to determine whether the weighted mean decrease in body mass index and sleep apnoea severity (measured by the apnoea-hypopnoea index) are larger in metabolic surgical studies than in non-surgical weight loss studies (diet, exercise and medication). However, heterogeneity across available trials, poor follow-up measures and a deficiency in comparative studies between surgical and non-surgical therapy precludes definitive statements regarding the relative benefits of surgical therapy.

Gill Rs et al ΣΗΜΑΝΤΙΚΗ ΜΕΤΑ-ΑΝΑΛΥΣΗ Αυστηρά κριτήρια επιλογής Μόνο 6 μελέτες που πληρούν τα κριτήρια Διαφορετικά scores Παρά ταύτα αισθητή βελτίωση του πόνου

Hypoglycaemia after gastric bypass surgery: diabetes remission in the extreme??? μεταγευματική υπογλυκαιμία = επιπλοκή χειρουργείου γαστρικής παράκαμψης σοβαρά νευρογλυκοπενικά συμπτώματα = απώλεια συνείδησης, επιληπτικές κρίσεις, τροχαία ατυχήματα θεραπεία: ακαρβόζη, ανάλογα σωματοστατίνης, διαζοξείδη??? συμπτώματα υπογλυκαιμίας 2-3 ώρες μετά φαγητό εμφάνιση διαταραχής 2-3 χρόνια μετά γαστρική παράκαμψη Μηχανισμοί μετά από γαστρική παράκαμψη... αύξηση κατά 10 φορές των μεταγευματικών συγκεντρώσεων των ινκρετινών GLP-1 και GIP παράκαμψη 12-δακτύλου, ταχεία διάβαση τροφών στο άπω λεπτό έντερο, άνοδος κυκλοφορούντων χολικών οξέων, νευροορμονικοί μηχανισμοί

Nationwide cohort study of post-gastric bypass hypoglycaemia including 5,040 patients undergoing surgery for obesity in 1986-2006 in Sweden Marsk R, Jonas E, Rasmussen F, Näslund E Diabetologia 2010;53:2307-311 Nationwide registry data from Sweden Roux-en-Y gastric bypass surgery RYGB (n=5,040) Vertical Banded Gastroplasty VBG (n=4,366) Gastric Banding GB (n=2,917) Incidence of hypoglycaemia between 1986 2006 Relative risk of hypoglycaemia was 2-7 fold higher after RYGB Absolute risk was small (only 0,2% of RYGB patients) No increase in hypoglycaemia after VBG or GB RESULTS

Gastric bypass surgery for obesity decreases the reward value of a sweet-fat stimulus as assessed in a progressive ratio task Alexander D Miras and Carel W le Roux Am J Clin Nutr 2012;96:467 73.

Conclusions The genetic variants in the ESR, FTO, and UCP2 genes may be considered as a screening tool prior to bariatric surgery to help clinicians predict weight loss or glycemic control outcomes for severely obese patients.

DIFFERENCES IN ENERGY EXPENDITURE, FAT MASS AND APPETITE SUPPRESSION AFTER GASTRIC BYPASS AND SLEEVE GASTRECTOMY FOR MORBID OBESITY Liaskos C 1, Alexiadou K 1, Tentolouris N 1, Balla I 1, Argyrakopoulou G 1, Alexandrou A 2, Diamantis T 2, Katsilambros N 1, Kokkinos A 1 ECO 2012

Conclusion: Roux-en-Y gastric bypass and sleeve gastrectomy lead to significant and comparable weight loss, decrease in energy expenditure, fat mass, and hunger, as well as an increase in satiety.

Θνητότης ανάλογα με την εμπειρία των κέντρων

Review of the key results from the Swedish Obese Subjects (SOS) trial: a prospective controlled intervention study of bariatric surgery LARS SJÖSTRÖM, doi: 10.1111/joim.12012 2012 The Association for the Publication of the Journal of Internal Medicine BMI does not predict the effects of surgical treatment on outcomes All current guidelines for bariatric surgery in obese individuals without [84-86] and with diabetes [72-75] are based on BMI alone or in combination with other criteria.. the value of BMI as a predictor of treatment effect does not seem to have been evaluated except in the SOS study.. BMI did thus not predict the effect of surgery on any of these endpoints By contrast, insulin predicted the treatment effect with respect to mortality (P for interaction=0.013) [35], cardiovascular events (P<0.001) [37] and incidence of diabetes (P=0.007) [38] (data not shown). There was also a strong impaired fasting glucose treatment interaction with respect to diabetes incidence (p=0.002)[38]. These findings suggest that guidelines for bariatric surgery need to be modified. In order to select those patients who are most likely to benefit from surgery, more importance should be given to metabolic variables and less to BMI.

Conserved Shifts in the Gut Microbiota Due to Gastric Bypass Reduce Host Weight and Adiposity Alice P. et al, ScienceTranslationalMedicine27 March 2013 Vol 5 Issue 178 In the first part of the experiment they performed gastric bypass surgery on obese mice; observed their subsequent weight loss, metabolic performance and gut microbes; and then compared their findings with the same measures in obese mice who had sham surgeries and remained overweight or who had sham surgeries and then lost weight on a diet of lowercalorie chow. Examining fecal samples and tissues from all three groups of animals, they found that the Roux-en-Y mice had changes in their gut microbes that weren't shared by the other two groups, including the lean mice who lost weight by dieting. The results suggested that the surgery itself -- rather than the weight of the animals -- was what altered the gut microbiota. For the second phase of the experiment, the team transplanted gut microbes from the three sets of mice into lean, germ-free mice. The ones who received bacteria from the Roux-en-Y mice lost weight and fat; the mice who got transplants from the other groups did not. Although the degree of weight loss by the RYGB microbiota into lean recipient mice is not as profound as the effect of RYGB in obese mice (5% versus 29% weight loss, respectively), these findings are consistent with the hypothesis that alterations in the gut microbiota after RYGBat least partially modulate body weight and adiposity.

Νεότερες Τεχνικές: Το Ενδοσκοπικά Τοποθετούμενο Σύστημα Endobarrier Gersin KS et al, Surg Innov 2007;14:275-278

ΣΩΜΑΤΟΜΕΤΡΙΚΑ ΣΤΟΙΧΕΙΑ ΝΕΟΣΥΛΛΕΚΤΩΝ ΕΠΑΓΓΕΛΜΑΤΙΩΝ ΟΠΛΙΤΩΝ ΝΑΥΤΙΚΟΥ, 2005 (n=718) ΔΜΣ 25 kg/m 2 40% ΔΜΣ 27 kg/m 2 21% ΔΜΣ 30 kg/m 2 9% ΠΕΡΙΦΕΡΕΙΑ ΜΕΣΗΣ 94 cm 31% ΠΕΡΙΦΕΡΕΙΑ ΜΕΣΗΣ 102 cm 12%